Principles and Practice of Hospital Medicine [2nd Edition] 0071843132, 9780071843133, 9780071843140

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Principles and Practice of Hospital Medicine

NOTICE Medicine is an ever-changing science. As new research and clinical experience broaden our knowledge, changes in treatment and drug therapy are required. The authors and the publisher o this work have checked with sources believed to be reliable in their e orts to provide in ormation that is complete and generally in accord with the standards accepted at the time o publication. However, in view o the possibility o human error or changes in medical sciences, neither the authors nor the publisher nor any other party who has been involved in the preparation or publication o this work warrants that the in ormation contained herein is in every respect accurate or complete, and they disclaim all responsibility or any errors or omissions or or the results obtained rom use o the in ormation contained in this work. Readers are encouraged to con irm the in ormation contained herein with other sources. For example, and in particular, readers are advised to check the product in ormation sheet included in the package o each drug they plan to administer to be certain that the in ormation contained in this work is accurate and that changes have not been made in the recommended dose or in the contraindications or administration. This recommendation is o particular importance in connection with new or in requently used drugs.

Principles and Practice of Hospital Medicine Second Edition Editors Sylvia C. McKean, MD, SFHM, FACP Deputy Editor or Editorial Projects, UpToDate Formerly: Leave o absence: Associate Pro essor o Medicine, Harvard Medical School Hospitalist Brigham and Women’s Hospital Boston, Massachusetts

John J. Ross, MD, CM, FIDSA Assistant Pro essor o Medicine Harvard Medical School Hospitalist Service Brigham and Women’s Hospital Boston, Massachusetts

Daniel D. Dressler, MD, MSc, SFHM, FACP Pro essor o Medicine Director, Internal Medicine Teaching Services Emory University Hospital Associate Program Director J. Willis Hurst Internal Medicine Residency Program Co-Director, Semmelweis Society Emory University School o Medicine Atlanta, Georgia

Danielle B. Scheurer, MD, MSCR, SFHM Chie Quality O icer and Hospitalist Associate Pro essor o Medicine Medical University o South Carolina Charleston, South Carolina

New York Chicago San Francisco Athens London Madrid Milan New Delhi Singapore Sydney Toronto

Mexico City

Principles and Practice o Hospital Medicine, Second Edition Copyright © 2017 by McGraw-Hill Education. All rights reserved. Printed in the United States o America. Except as permitted under the United States Copyright Act o 1976, no part o this publication may be reproduced or distributed in any orm or by any means, or stored in a data base or retrieval system, without the prior written permission o the publisher. Previous edition copyright © 2012 by The McGraw-Hill Companies, Inc. 1 2 3 4 5 6 7 8 9 DOW 21 20 19 18 17 16 ISBN 978-0-07-184313-3 MHID 0-07-184313-2 This book was set in Myriad pro by Cenveo Publisher Services. The editors were Amanda Fielding and Kim J. Davis. The production supervisor was Richard Ruzycka. Project management was provided by Vastavikta Sharma, Cenveo Publisher Services. The designer was Alan Barnett; the cover designer was Dreamit, Inc. RR Donnelley was printer and binder.

Library o Congress Cataloging-in-Publication Data Names: McKean, Sylvia C., editor. | Ross, John J. (John James), 1966-editor. | Dressler, Daniel D., editor. | Scheurer, Danielle, editor. Title: Principles and practice o hospital medicine / editors, Sylvia C. McKean, John J. Ross, Daniel D. Dressler, Danielle B. Scheurer. Description: Second edition. | New York : McGraw-Hill Education Medical, [2017] | Includes bibliographical re erences and index. Identi iers: LCCN 2016022668 (print) | LCCN 2016023825 (ebook) | ISBN 9780071843133 (hardcover : alk. paper) | ISBN 0071843132 (hardcover : alk. paper) | ISBN 9780071843140 (ebook) Subjects: | MESH: Hospital Medicine—methods | Hospitalization | Inpatients | Hospitalists Classi ication: LCC RA972 (print) | LCC RA972 (ebook) | NLM WX 21 | DDC 362.11—dc23 LC record available at https://lccn.loc.gov/2016022668

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Contributors ................................................................................................. xiii

19 Tools to Identify Problems and Reduce Risks . . . . . . . . . . 118

Section Reviewers ..................................................................................xxxix

20 Preventing and Managing Adverse Patient Events: Patient Safety and the Hospitalist . . . . . . . . . . . . . 124

PART I: THE SPECIALTY OF HOSPITAL MEDICINE AND SYSTEMS OF CARE SECTION 1

24 Best Practices in Physician Recruitment and Retention . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 150

2 Value-Based Health Care for Hospitalists . . . . . . . . . . . . . . . 10

25 Teamwork in Leadership and Practice-Based Management . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 157

3 Racial/Ethnic Disparities in Hospital Care . . . . . . . . . . . . . . . 18

26 Negotiation and Conflict Resolution . . . . . . . . . . . . . . . . . . 164

...............

23

5 Professionalism in Hospital Medicine . . . . . . . . . . . . . . . . . . 29

SECTION 6

6 Principles of Leadership . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33

Critical Decision Making at the Point of Care

8 Diagnostic Reasoning and Decision Making . . . . . . . . . . . . 45 9 Principles of Evidence-Based Prescribing . . . . . . . . . . . . . . . 56 10 Summary Literature: Practice Guidelines and Systematic Reviews . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 62 11 Practical Considerations of Incorporating Evidence into Clinical Practice . . . . . . . . . . . . . . . . . . . . . . . . 70

28 Consultation, Comanagement, Time-Based, and Palliative Care Billing . . . . . . . . . . . . . . . . . . . . . . . . . . . . 182 29 Billing for Procedures and Use of Modifiers in Inpatient Practice . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 192 30 Billing in the Teaching Setting and Billing with Advanced Practice Providers . . . . . . . . . . . . . . . . . . . . 198 31 Hospital-Driven Documentation 32 Taming the ICD-10 Monster

SECTION 7

Transitions of Care

12 Care Transitions into the Hospital: Health Care Centers, Emergency Department, Outside Hospital Transfers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 79 13 Care Transitions within the Hospital: The Hand-Off

Billing, Coding, and Clinical Documentation

27 Professional Coding and Billing Guidelines for Clinical Documentation . . . . . . . . . . . . . . . . . . . . . . . . . . 173

7 Principles of Evidence-Based Medicine and Quality of Evidence . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 39

SECTION 3

T

Practice Management

23 Building, Growing and Managing a Hospitalist Practice . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 139

1 The Face of Health Care: Emerging Issues for Hospitalists . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5

SECTION 2

E

22 The Role of Information Technology in Hospital Quality and Safety . . . . . . . . . . . . . . . . . . . . . . . . . . 134

SECTION 5

The Value and Values of Hospital Medicine

4 Comanagement of Orthopedic Patients

N

Acknowledgments ..................................................................................... xlv

21 Principles and Models of Quality Improvement: Plan-Do-Study-Act . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 130

T

Preface ...........................................................................................................xliii

S

Foreword ......................................................................................................... xli

O

18 Standardization and Reliability . . . . . . . . . . . . . . . . . . . . . . . 113

N

Editors ...............................................................................................................xi

C

CONTENTS

.....

84

.....................

204

.........................

210

Principles of Medical Ethics and Medical-Legal Concepts

33 Common Indications for Ethics Consultation

..........

217

34 Medical-Legal Concepts: Advance Directives and Surrogate Decision Making . . . . . . . . . . . . . . . . . . . . . . 224 35 Medical Malpractice . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 231

14 Care Transitions at Hospital Discharge . . . . . . . . . . . . . . . . . 90

SECTION 8 SECTION 4

Patient Safety and Quality Improvement

15 Principles of Patient Safety: Intentional Design and Culture . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 99

Professional Development

36 Principles of Adult Learning and Continuing Medical Education . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 243 37 Cultural Competence

...............................

246

16 Patient-Centered Care . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 104

38 Career Design and Development in Academic and Community Settings . . . . . . . . . . . . . . . . . . . . . . . . . . . . 253

17 Harnessing Data to Make Quality Improvement Decisions: Measurement and Measures . . . . . . . . . . . . . . . 110

39 Mentorship of Peers and Trainees . . . . . . . . . . . . . . . . . . . . 257 40 Research in the Hospital . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 264 v

41 For Individuals and Practices: Career Sustainability and Avoiding Burnout

.................

273

65 Management of Common Perioperative Complications in Orthopedic Surgery. . . . . . . . . . . . . . . . . 437 66 Transplant Surgery. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 447 67 Urology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 453

PART II: MEDICAL CONSULTATION SECTION 1

Surgery

N

E

T

N

O

C

42 Physiologic Response to Surgery . . . . . . . . . . . . . . . . . . . . . 283 43 Perioperative Hemostasis . . . . . . . . . . . . . . . . . . . . . . . . . . . . 286

68 Postacute Care Rehabilitation Options . . . . . . . . . . . . . . . . 463

44 Postoperative Complications

292

69 Physical Therapy and Rehabilitation . . . . . . . . . . . . . . . . . . 469

45 Surgical Tubes and Drains . . . . . . . . . . . . . . . . . . . . . . . . . . . 297

70 The Role of Speech/Language Pathologists in Dysphagia Management . . . . . . . . . . . . . . . . . . . . . . . . . . . . 476

........................

................................

300

S

T

46 Surgical Critical Care

SECTION 2

71 Incontinence . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 482 72 Pressure Ulcers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 491

Anesthesia

47 Anesthesia: Choices and Complications . . . . . . . . . . . . . . . 309

73 Patient Safety and Quality Improvement in Postacute Care . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 497

48 Perioperative Pain Management

74 Hospice . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 505

SECTION 3

.....................

313

Perioperative Risk Assessment and Management

49 Role of the Medical Consultant . . . . . . . . . . . . . . . . . . . . . . . 325 50 Preoperative Cardiac Risk Assessment and Perioperative Management . . . . . . . . . . . . . . . . . . . . . . . . . . 329

PART IV: APPROACH TO THE PATIENT AT THE BEDSIDE 75 Acute Abdominal Pain 76 Acute Back Pain

..............................

513

....................................

522

51 Perioperative Pulmonary Risk Assessment and Management . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 336

77 Evaluation of Anemia

52 Perioperative Risk Assessment and Management of the Diabetic Patient . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 342

79 Chest Pain

53 Preoperative Evaluation of Liver Disease . . . . . . . . . . . . . . 348 54 Preoperative Assessment of Patients with Hematologic Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 352

SECTION 4

.................

.........................................

80 Constipation

533 547

.......................................

556

81 Delirium

...........................................

563

82 Diarrhea

...........................................

572

83 Disorders of the Eye . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 579 85 Dyspnea

...............................

587

...........................................

595

86 Edema . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 604 361

56 Venous Thromboembolism (VTE) Prophylaxis for Nonorthopedic Surgery . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 368 57 Postoperative Blood Transfusion . . . . . . . . . . . . . . . . . . . . . 373 58 Nutrition and Metabolic Support . . . . . . . . . . . . . . . . . . . . . 377 59 Cardiac Complications after Noncardiac Surgery. . . . . . . 385 60 Management of Postoperative Pulmonary Complications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 391 61 Assessment and Management of Patients with Renal Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 397 62 Postoperative Neurologic and Psychiatric Complications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 412

SECTION 5

...............................

78 Bleeding and Coagulopathy . . . . . . . . . . . . . . . . . . . . . . . . . 539

84 Dizziness and Vertigo

Prevention, Assessment, and Management of Common Complications in Noncardiac Surgery

55 Antimicrobial Prophylaxis in Surgery

vi

PART III: REHABILITATION AND SKILLED NURSING CARE

Specialty Consultation—What the Consulting Hospitalist Needs to Know

87 Falls . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 613 88 Fever and Rash

.....................................

620

89 Headache . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 625 90 Hemoptysis

........................................

91 Hypertensive Urgencies and Emergencies

............

636 641

92 Hyperthermia and Fever. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 647 93 Hypotension

.......................................

657

94 Hypothermia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 665 95 Hypoxia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 669 96 Sleep Disturbance in the Hospitalized Patient . . . . . . . . . 676 97 Nausea and Vomiting

...............................

98 Numbness: A Localization-Based Approach 99 Pain

689

...........

694

...............................................

701

100 Suspected Intoxication and Overdose

................

709

...........................................

714

63 Surgical Management of Obesity . . . . . . . . . . . . . . . . . . . . . 421

101 Syncope

64 Common Postoperative Complications in Neurosurgery . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 430

102 Tachycardia

........................................

729

103 The Geriatric History and Physical Examination . . . . . . . . 740

104 The Neurologic Examination . . . . . . . . . . . . . . . . . . . . . . . . . 747 .................

754

106 Weakness: How to Localize the Problem . . . . . . . . . . . . . . 763

Critical Care

137 Inpatient Cardiac Arrest and Cardiopulmonary Resuscitation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1037

PART V: DIAGNOSTIC TESTING AND PROCEDURES

109 Elevated Liver Biochemical and Function Tests . . . . . . . . 796 110 Pulmonary Function Testing . . . . . . . . . . . . . . . . . . . . . . . . . 805 111 Urinalysis and Urine Electrolytes

SECTION 2

.....................

814

112 Introduction to Radiology . . . . . . . . . . . . . . . . . . . . . . . . . . . 825 113 Patient Safety Issues in Radiology . . . . . . . . . . . . . . . . . . . . 831 114 Basic Chest Radiography (CXR) . . . . . . . . . . . . . . . . . . . . . . . 838 115 Advanced Cardiothoracic Imaging

...................

853

...........................

864

117 Advanced Abdominal Imaging . . . . . . . . . . . . . . . . . . . . . . . 870 118 Neurologic Imaging . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 876 119 Interventional Radiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . 884

SECTION 3

143 Prevention in the Intensive Care Unit Setting . . . . . . . . 1094

SECTION 3

Procedures

145 Adverse Cutaneous Drug Reactions

................

146 Psoriasis and Other Papulosquamous Disorders

.....

1114 1125

147 Diabetic Foot Infections . . . . . . . . . . . . . . . . . . . . . . . . . . . 1131 148 Venous Ulcers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1138 149 Dermatologic Findings in Systemic Disease

SECTION 4

.........

1145

............................

1171

Endocrinology

150 Glycemic Emergencies

151 Inpatient Management of Diabetes and Hyperglycemia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1178 152 Thyroid Emergencies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1184

120 Vascular Access . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 891

153 Adrenal Insufficiency . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1191

121 Intubation and Airway Support

154 Pituitary Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1198

......................

895

122 Arterial Blood Gas and Placement of A-line . . . . . . . . . . . . 901 123 Feeding Tube Placement . . . . . . . . . . . . . . . . . . . . . . . . . . . . 905 124 Thoracentesis

......................................

909

SECTION 5

Gastroenterology

155 GERD and Esophagitis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1209

125 Lumbar Puncture . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 914

156 Upper Gastrointestinal Bleeding

126 Paracentesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 918

157 Acute Pancreatitis

127 Arthrocentesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 921

...................

1217

................................

1227

158 Jaundice, Obstruction, and Acute Cholangitis 159 Acute Liver Disease

.......

1232

...............................

1239

160 Cirrhosis and Its Complications

PART VI: CLINICAL CONDITIONS IN THE INPATIENT SETTING

163 Large Bowel Disorders

941

130 Myocarditis, Pericardial Disease, and Cardiac Tamponade . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 954 ..............................

965

132 Supraventricular Tachyarrhythmias . . . . . . . . . . . . . . . . . . . 980 133 Bradycardia

1269

............................

1290

164 Inflammatory Bowel Disease . . . . . . . . . . . . . . . . . . . . . . . 1308

.......................................

131 Valvular Heart Disease

.............

1253

162 Small Bowel Disorders. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1279

128 Acute Coronary Syndromes . . . . . . . . . . . . . . . . . . . . . . . . . . 929 129 Heart Failure

....................

161 Acute Lower Gastrointestinal Bleeding

Cardiovascular Medicine

SECTION 1

O

Dermatology

144 Flushing and Urticaria . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1105

Radiology

116 Basic Abdominal Imaging

142 Acute Respiratory Distress Syndrome . . . . . . . . . . . . . . . 1085

N

141 Sepsis and Shock . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1074

T

108 The Resting Electrocardiogram . . . . . . . . . . . . . . . . . . . . . . . 776

E

140 Mechanical Ventilation . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1065

N

107 Basic Diagnostic Tests . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 771

T

139 Pain, Agitation and Delirium in the Critical Care Setting . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1055

C

138 Acute Respiratory Failure . . . . . . . . . . . . . . . . . . . . . . . . . . 1047

Interpretation of Common Tests

SECTION 1

SECTION 2

S

105 Using Prognosis to Guide Treatment

136 Pacemakers, Defibrillators, and Cardiac Resynchronization Devices in Hospital Medicine . . . . . 1025

........................................

996

SECTION 6

Geriatrics

165 Principles of Geriatric Care . . . . . . . . . . . . . . . . . . . . . . . . . 1323 166 Agitation in Older Adults . . . . . . . . . . . . . . . . . . . . . . . . . . 1330 167 Elder Mistreatment

...............................

1336

168 Malnutrition and Weight Loss in Hospitalized Older Adults. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1346

134 Ventricular Arrhythmias . . . . . . . . . . . . . . . . . . . . . . . . . . . 1003 135 Cardioversion

....................................

1015

vii

SECTION 7

Hematology

SECTION 10

169 Abnormalities in Red Blood Cells . . . . . . . . . . . . . . . . . . . 1353

207 Coma and Disorders of Consciousness . . . . . . . . . . . . . . 1667

170 Disorders of the White Cell

208 Intracranial Hemorrhage and Related Conditions

........................

1373

172 Approach to Patients with Bleeding Disorders . . . . . . . 1392

211 Seizures . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1700

173 Hypercoagulable States . . . . . . . . . . . . . . . . . . . . . . . . . . . 1399

212 Multiple Sclerosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1712

174 Hematologic Malignancies

213 Peripheral Neuropathy . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1719

........................

1405

Oncology

210 Parkinson’s Disease and Related Disorders . . . . . . . . . . 1690

SECTION 11

Palliative Care

175 Overview of Cancer and Treatment . . . . . . . . . . . . . . . . . 1431

214 Principles of Palliative Care

176 Oncologic Emergencies

1436

215 Communication Skills for End-of-Life Care

..........

1733

177 Approach to the Patient with Suspected Malignancy . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1443

216 Domains of Care: Physical Aspects of Care

..........

1740

.........................

1756

...........................

178 Breast, Ovary, and Cervical Cancer. . . . . . . . . . . . . . . . . . 1454 179 Men’s Cancers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1458 180 Cancers of the Kidney, Renal Pelvis, and Ureter . . . . . . 1463

217 Care of the Dying Patient

SECTION 12

........................

1727

Pregnancy

181 Oncologic Issues of the Aerodigestive Tract . . . . . . . . . 1468

218 Overview of Physiologic Changes of Pregnancy

.....

1767

182 Gastrointestinal Cancers . . . . . . . . . . . . . . . . . . . . . . . . . . . 1474

219 Medication Management

.........................

1771

183 Immune-Related Adverse Events (irAEs) in Cancer Patients . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1477

220 Critical Care of the Pregnant Patient . . . . . . . . . . . . . . . . 1781 221 Common Medical Problems in Pregnancy. . . . . . . . . . . 1786 222 Postpartum Consultation for Common Complaints

SECTION 9

..

1807

Infectious Disease

184 Fundamentals of Antibiotics . . . . . . . . . . . . . . . . . . . . . . . 1489

SECTION 13

Psychiatry

185 Antibiotic Resistance . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1498

223 Mood and Anxiety Disorders . . . . . . . . . . . . . . . . . . . . . . . 1813

186 Community-Acquired Pneumonia . . . . . . . . . . . . . . . . . . 1503

224 Combat Stress and Related Disorders . . . . . . . . . . . . . . . 1827

187 Health Care and Hospital-Acquired Pneumonia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1514

225 Assessment and Management of Psychosis

188 Intravascular Catheter-Related Infections: Management and Prevention . . . . . . . . . . . . . . . . . . . . . . 1519

227 The Suicidal Patient . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1848

189 Infective Endocarditis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1528

229 Approach to the Patient with Multiple Unexplained Somatic Symptoms . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1861

190 Clostridium difficile–Associated Disease (CDAD) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1537 191 Peritonitis and Intra-Abdominal Abscess . . . . . . . . . . . . 1542 192 Meningitis and Encephalitis. . . . . . . . . . . . . . . . . . . . . . . . 1549 193 Osteomyelitis and Septic Arthritis . . . . . . . . . . . . . . . . . . 1557 194 Prosthetic Joint Infections . . . . . . . . . . . . . . . . . . . . . . . . . 1564 195 Sexually Transmitted Infections . . . . . . . . . . . . . . . . . . . . 1574

226 Eating Disorders

.........

1833

.................................

1841

228 The Difficult Patient

SECTION 14

..............................

1853

Pulmonary and Allergy Immunology

230 Allergy and Anaphylaxis . . . . . . . . . . . . . . . . . . . . . . . . . . . 1871 231 Asthma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1876 232 Chronic Obstructive Pulmonary Disease

............

1887

196 Skin and Soft Tissue Infections . . . . . . . . . . . . . . . . . . . . . 1582

233 Interstitial Lung Diseases/Diffuse Parenchymal Lung Diseases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1898

197 Urinary Tract Infections. . . . . . . . . . . . . . . . . . . . . . . . . . . . 1589

234 Cystic Fibrosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1905

198 Viral Infections

235 Sleep Apnea and Obesity Hypoventilation Syndrome . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1915

...................................

199 Tickborne Infections

..............................

1596 1604

200 Tuberculosis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1612

236 Pleural Diseases

201 Candida and Aspergillus

237 Pulmonary Hypertension

...........................

1618

202 Histoplasmosis, Blastomycosis, Coccidioidomycosis, and Other Dimorphic Fungi. . . . . . . . . . . . . . . . . . . . . . . . 1625 203 The Hospitalized Patient with HIV . . . . . . . . . . . . . . . . . . 1634 204 Infections of the Immunocompromised Host 205 Fever in the Returning Traveler

.......

1646

....................

1653

206 Undiagnosed Fever in Hospitalized Patients

viii

1674

209 Transient Ischemic Attack and Stroke . . . . . . . . . . . . . . . 1681

C O N T E N T

...

171 Quantitative Abnormalities of Platelets: Thrombocytopenia and Thrombocytosis . . . . . . . . . . . . 1381

SECTION 8

S

Neurology

........

1659

SECTION 15

.................................. .........................

1923 1932

Renal

238 Acid-Base Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1943 239 Acute Kidney Injury . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1952 240 Calcium Disorders

................................

1961

241 Potassium and Magnesium Disorders . . . . . . . . . . . . . . . 1972 242 Disorders of Sodium and Water Balance

............

1982

243 Kidney Stones . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1993 ..........................

2000

245 Chronic Kidney Disease and Dialysis . . . . . . . . . . . . . . . . 2008

252 Venous Thromboembolism Prophylaxis for Hospitalized Medical Patients . . . . . . . . . . . . . . . . . . . . . . 2077 253 Diagnosis and Treatment of Venous Thromboembolism . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2081 254 Anticoagulant Therapy

Rheumatology

...........................

2093

255 Diseases of the Aorta . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2107 256 Acute and Chronic Lower Limb Ischemia . . . . . . . . . . . . 2115

247 Gout, Pseudogout, and Osteoarthritis

257 Vasculitis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2121

SECTION 17

Toxicology and Addiction

250 Drug Overdose and Withdrawal . . . . . . . . . . . . . . . . . . . . 2057 251 Addiction of Prescription and Nonprescription Drugs . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2070

T

249 Rheumatoid Arthritis and Other Inflammatory Arthritides . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2046

Online Chapters

E

2033

N

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e1 e2 e3 e4 e5

T

2023

Global Health and Hospital Medicine The Economics of Hospital Care Principles of Medical Ethics The Core Competencies in Hospital Medicine Bioterrorism

Index

.................................................

S

248 Systemic Lupus Erythematosus

..............

N

246 Rheumatologic Emergencies. . . . . . . . . . . . . . . . . . . . . . . 2017

C

SECTION 16

Vascular Medicine

O

244 Secondary Hypertension

SECTION18

2129

ix

EDITORS Sylvia C. McKean, MD, SFHM, FACP John J. Ross, MD, CM, FIDSA Daniel D. Dressler, MD, MSc, SFHM, FACP Danielle B. Scheurer, MD, MSCR, SFHM

xi

CONTRIBUTORS

Aaron W. Aday, MD Division o Cardiovascular Medicine Department o Medicine Brigham and Women’s Hospital Boston, Massachusetts [255]

Bhavin Adhyaru, MD Emory University School o Medicine Atlanta, Georgia [10]

Kush Agrawal, MD Advanced Endovascular and Structural Interventional Fellow VIVA Physicians El Camino Hospital Mountain View, Cali ornia [101]

Mikhail Akbashev, MD Assistant Pro essor o Medicine Emory University School o Medicine Atlanta, Georgia [11]

A saneh Alavi, MD, MSc, FRCPC Department o Medicine (Dermatology) University o Toronto Toronto, Ontario, Canada [148]

G. Caleb Alexander, MD, MS Associate Pro essor o Epidemiology and Medicine Bloomberg School o Public Health Johns Hopkins University Baltimore, Maryland [e3]

Anne E. Allan, MD Miraca Li e Sciences Irving, Texas [146]

Ashwin Ananthakrishnan, MD Attending Physician Massachusetts General Hospital Instructor in Medicine, Harvard Medical School Boston, Massachusetts [183]

O N T R I B

Assistant Pro essor o Anesthesiology and Pain Medicine Director Pain Medicine Fellowship Medical College o Wisconsin Milwaukee, Wisconsin [99]

U

Meredith C. B. Adams, MD, MS

T

Associate Pro essor o Surgery Division o Surgical Oncology Michael E. DeBakey Department o Surgery Research Scientist The Houston Center or Quality o Care &Utilization Studies Director Liver Tumor Program, Michael E. DeBakey VAMC Baylor College o Medicine Houston, Texas [55]

O

Pain Medicine Fellowship Medical College o Wisconsin Milwaukee, Wisconsin [99]

R

Daniel A. Anaya, MD

S

Samer Abdel-Aziz, MD

C

Numbers in brackets refer to the chapters written or co-written by the contributor.

Douglas S. Ander, MD Pro essor o Emergency Medicine Emory University School o Medicine Atlanta, Georgia [121]

Eddy Ang, MD Instructor in Medicine Harvard Medical School Division o Gerontology Beth Israel Deaconess Medical Center Boston, Massachusetts Department o Medicine, Hebrew SeniorLi e Roslindale, Massachusetts [68]

Kelly Armstrong, PhD Senior Clinical Ethicist Memorial Health System Adjunct Assistant Pro essor Department o Medical Humanities SIU School o Medicine Spring eld, Illinois [34]

Vineet M. Arora, MD, MAPP Associate Pro essor and Assistant Dean or Scholarship and Discovery Director GME Clinical Learning Environment Innovation Pritzker School o Medicine University o Chicago Chicago, Illinois [13]

Cameron Ashbaugh, MD Assistant Pro essor Harvard Medical School Division o In ectious Diseases Brigham and Women’s Hospital Boston, Massachusetts [196]

Saima Aslam, MD, MS Assistant Pro essor Director Solid Organ Transplant In ectious Diseases service Division o In ectious Diseases University o Cali ornia, San Diego San Diego, Cali ornia [188]

xiii

C O N T R I B U T O R S

Mark J. Ault, MD

Robert B. Baron, MD, MS

Pro essor o Medicine University o Cali ornia Los Angeles School o Medicine Department o Medicine Cedars-Sinai Medical Center Los Angeles, Cali ornia [125]

Pro essor o Medicine Associate Dean or Graduate and Continuing Medical Education Vice Chie , Division o General Internal Medicine University o Cali ornia San Francisco School o Medicine San Francisco, Cali ornia [36]

Patrick Avila, MD, MPhil, MPH

Tom Baudendistel, MD, FACP

Internal Medicine Resident Physician Brigham and Women’s Hospital Boston, Massachusetts [160]

Internal Medicine Residency Program Director Kaiser Permanente Oakland, Cali ornia [39]

Vasilis C. Babaliaros, MD

Mihaela H. Bazalakova, MD, PhD

Pro essor o Medicine and Surgery Co-Director Emory Structural Heart and Valve Center Emory University Hospital Atlanta, Georgia [131]

Assistant Pro essor Department o Neurology Center or Sleep Medicine and Sleep Research University o Wisconsin-Madison Madison, Wisconsin [96]

Lindsey R. Baden, MD

Joshua A. Beckman, MD, MSc

Associate Pro essor Harvard Medical School In ectious Diseases Division Brigham and Women’s Hospital and Dana-Farber Cancer Institute Boston, Massachusetts [204]

Section o Vascular Medicine Cardiovascular Division Vanderbilt University Medical Center Nashville, Tennessee [255]

Meridale V. Baggett, MD

Birmingham, Michigan [58]

Assistant Pro essor o Medicine Harvard Medical School Inpatient Clinician Educator Service Department o Medicine Massachusetts General Hospital Boston, Massachusetts [78]

James L. Bailey, MD Pro essor Emory University School o Medicine Atlanta, Georgia [241]

Stephen J. Balevic, MD Adult and Pediatric Rheumatology Fellow Duke University Medical Center Durham, North Carolina [248]

Peter A. Banks, MD Pro essor o Medicine Harvard Medical School Director o the Center or Pancreatic Disease Division o Gastroenterology, Hepatology and Endoscopy Department o Medicine Brigham and Women’s Hospital Boston, Massachusetts [157]

Aditya Bardia, MD, MPH Assistant Pro essor Harvard Medical School Attending Physician Massachusetts General Hospital Cancer Center Boston, Massachusetts [177, 183]

Maria F. Barile, MD Clinical Instructor in Radiology Harvard Medical School Thoracic Radiologist, Brigham and Women’s Hospital Boston, Massachusetts [114, 115]

xiv

Nicole M. Bedi, RD, CNSC Laurence Beer, MD, SFHM Emory University School o Medicine Atlanta, Georgia [8]

Michael Belkin, MD Division o Vascular Surgery Brigham and Women’s Hospital Boston, Massachusetts [256]

Elie F. Berbari, MD Pro essor o Medicine Mayo Clinic College o Medicine Rochester, Minnesota [194]

Colm Bergin, MD, FRCPI, FRCP, FIDSA Clinical Pro essor o Medicine Trinity College Dublin Consultant Physician in In ectious Diseases Associate Director Wellcome-Health Research Board Clinical Research Facility St. James’s Hospital Dublin, Ireland [195]

Aaron L. Berkowitz, MD, PhD Department o Neurology Brigham and Women’s Hospital Harvard Medical School Boston, Massachusetts [98]

Rachelle E. Bernacki, MD, MS Assistant Pro essor o Medicine Harvard Medical School Director o Quality Initiatives Palliative Care Dana-Farber Cancer Institute Brigham and Women’s Hospital Ariadne Labs Boston, Massachusetts [105, 214]

Robert A. Bessler, MD

Ghada Bourjeily, MD

CEO Sound Physicians Tacoma, Washington [23, 25]

Associate Pro essor o Medicine The Warren Alpert Medical School o Brown University The Miriam Hospital Pulmonary, Critical Care, Obstetric Medicine Department o Medicine Providence, Rhode Island [220]

Kenneth D. Bishop, MD, PhD

Division o Urology The Warren Alpert Medical School o Brown University Providence, Rhode Island [180]

Assistant Pro essor o Medicine Division o Hematology/Oncology Rhode Island Hospital The Warren Alpert Medical School o Brown University Providence, Rhode Island [176]

Ioannis A. Bliziotis, MD, PhD, MSc Internal Medicine and In ectious Diseases Specialist Senior Researcher Al a Institute o Biomedical Sciences Athens, Greece [184]

Arline D. Bohannon, MD Associate Pro essor o Internal Medicine Virginia Commonwealth University Richmond, Virginia [103]

Peter A. Boling, MD Pro essor o Internal Medicine Virginia Commonwealth University Health System Richmond, Virginia [103]

Marcy B. Bolster, MD Associate Pro essor Harvard Medical School Director Rheumatology Fellowship Training Program Massachusetts General Hospital Boston, Massachusetts [248, 249]

Diego F. Bonilla Arcos, MD Pulmonary Critical Care Boston University Pulmonary Center Boston Medical Center Boston, Massachusetts [237]

Joanna M. Bonsall, MD, PhD Assistant Pro essor o Medicine Division o Hospital Medicine Emory University School o Medicine Atlanta, Georgia [12]

O N T R I B U

Ursula C. Brewster, MD

T

Assistant Pro essor The Warren Alpert Medical School o Brown University Department o Obstetric Medicine, Women’s Medicine Collaborative Miriam Hospital Providence, Rhode Island [222]

C

Assistant Pro essor Harvard Medical School Director Gastrointestinal Radiology Brigham and Women’s Hospital Boston, Massachusetts [116, 117]

O

Courtney Bilodeau, MD, FACP

John M. Braver, MD

Associate Pro essor o Medicine Section o Nephrology Yale University School o Medicine New Haven, Connecticut [245]

R

Dorothy L. and Daniel H. Silberberg Pro essor o Medicine Pro essor o Pharmacology Columbia University Medical College Chie , Division o Endocrinology Director Metabolic Bone Diseases Program Columbia University Medical Center New York, New York [240]

S

John P. Bilezikian, MD

Joseph Brito, MD

Jared R. Brosch, MD, MS Assistant Pro essor o Neurology Indiana University School o Medicine Indianapolis, Indiana [192]

Katherine L. Brown, MD, MPH Suncoast Dermatology Orlando, Florida [148]

Tod A. Brown, MD Assistant Pro essor Anesthesia and Perioperative Medicine Medical University o South Carolina Charleston, South Carolina [62]

Avery L. Buchholz, MD, MPH Department o Neurosurgery Medical University o South Carolina Charleston, South Carolina [64]

Tina Budnitz, MPH, MHM Senior Advisor Society Hospital Medicine Philadelphia, Pennsylvania [e4]

Robert Burakof , MD, MPH Associate Pro essor o Medicine Division o Gastroenterology, Hepatology, and Endoscopy Brigham and Women’s Hospital Harvard Medical School Boston, Massachusetts [155]

T. Karl Byrne, MD, FACS Pro essor o Surgery Director Bariatric Surgery Program Medical University o South Carolina Charleston, South Carolina [63]

xv

Amanda Caissie, MD, PhD, FRCPC

Olga S. Chajewski, MD

Department o Radiation Oncology Dalhousie University Saint John Regional Hospital Saint John, New Brunswick, Canada [215]

Department o Pathology and Laboratory Medicine Medical University o South Carolina Charleston, South Carolina [57]

Evelyn Cantillo, MD, MPH

Assistant Pro essor o Medicine Division o Gastroenterology, Hepatology, and Endoscopy Harvard Medical School Brigham and Women’s Hospital Boston, Massachusetts [155]

N

O

C

Clinical Instructor o Obstetrics and Gynecology Program in Women’s Oncology Women &In ants’Hospital o Rhode Island The Warren Alpert Medical School o Brown University Providence, Rhode Island [178]

T

Stephanie M. Cantu, MD

O

T

U

B

I

R

Department o Medicine Brigham and Women’s Hospital Boston, Massachusetts [109]

S

R

Mitchell S. Cappell, MD, PhD

Arjun S. Chanmugam, MD, MBA Associate Pro essor o Emergency Medicine Johns Hopkins University School o Medicine Baltimore, Maryland [79]

Helen Chen, MD

Pro essor o Medicine Oakland University William Beaumont School o Medicine Chie , Division o Gastroenterology and Hepatology Department o Medicine William Beaumont Hospital Royal Oak, Michigan [163]

Assistant Pro essor o Medicine Harvard Medical School Division o Gerontology Beth Israel Deaconess Medical Center Chie Medical O cer Hebrew SeniorLi e Boston, Massachusetts [73]

Alexander R. Carbo, MD, FACP, SFHM

Kenneth K. Chen, MD, FRACP

Assistant Pro essor o Medicine Harvard Medical School Hospitalist Beth Israel Deaconess Medical Center Boston, Massachusetts [15]

Assistant Pro essor o Medicine and OB/GYN Division o Obstetric and Consultative Medicine The Warren Alpert Medical School o Brown University Providence, Rhode Island [221]

Teresa L. Carman, MD

Instructor in Dermatology Harvard Medical School Massachusetts General Hospital Boston, Massachusetts [145]

Assistant Pro essor o Medicine Case Western Reserve University School o Medicine Director Vascular Medicine University Hospitals Case Medical Center Cleveland, Ohio [86]

Patrick J. Cawley, MD, MHM CEO MUSC Health Vice President or Health A airs Medical University o South Carolina Charleston, South Carolina [1]

Laura K. Certain, MD, PhD Instructor in Medicine Harvard Medical School Division o In ectious Diseases Massachusetts General Hospital Boston, Massachusetts [193]

Matthew E. Certain, MD Interventional and Peripheral Cardiologist Southeast Georgia Health Systems Brunswick, Georgia [130]

Sukit Chaiyachati, MD Assistant Pro essor o Medicine Division o Hospital Medicine Emory University School o Medicine Atlanta, Georgia [90]

xvi

Walter W. Chan, MD, MPH

Steven T. Chen, MD, MPH

Xi Chen, MD, PhD Neurology Department Atrius Health Boston, Massachusetts [96]

Nishay Chitkara, MD Assistant Pro essor o Medicine NYU Langone Medical Center/Bellevue Hospital Department o Medicine Division o Pulmonary Critical Care and Sleep Medicine New York, New York [143]

Louisa W. Chiu, MD Assistant Pro essor o Surgery Michael E. DeBakey Department o Surgery Baylor College o Medicine Houston, Texas [55]

Elbert B. Chun, MD Assistant Pro essor Division o Hospital Medicine Department o Internal Medicine Emory University School o Medicine Emory University Hospital Atlanta, Georgia [132]

Roger P. Clark, DO

Frank E. Corrigan, III, MD

Assistant Pro essor o Medicine Division o Geographic Medicine and In ectious Diseases Tu ts Medical Center Consultant, In ectious Diseases Brigham and Women’s Faulkner Hospital Boston, Massachusetts [199]

Cardiology Fellow Emory University School o Medicine Atlanta, Georgia [101]

Steven L. Cohn, MD, FACP, SFHM Pro essor o Clinical Medicine University o Miami Miller School o Medicine Medical Director UHealth Preoperative Assessment Center Director Medical Consultation Services University o Miami Hospital and Jackson Memorial Hospital Miami, Florida [49, 50]

Lauren Colbert, MD Fellow Radiation Oncology MD Anderson Cancer Center Houston, Texas [182]

Alexandra Columbus, MD Resident General Surgery Brigham and Women’s Hospital Boston, Massachusetts [45]

Jose F. Condado, MD, MS Cardiology Research Fellow Structural Heart and Valve Center Division o Cardiology Emory University School o Medicine Atlanta, Georgia [131]

Nicholas J. Connors, MD Assistant Pro essor o Medicine Medical University o South Carolina Division o Emergency Medicine Section o Medical Toxicology Charleston, South Carolina [100]

Darin J. Correll, MD Assistant Pro essor o Anesthesia Harvard Medical School Director Postoperative Pain Management Service Department o Anesthesiology, Perioperative, and Pain Medicine Chair, Acute Pain Committee Brigham and Women’s Hospital Boston, Massachusetts [48]

Lisa Criscione -Schreiber, MD, MEd Associate Pro essor o Medicine Rheumatology Training Program Director Duke University Medical Center Duke University School o Medicine Durham, North Carolina [248, 249]

C O N T R I B U T

Pro essor o Medicine (Cardiology) R. Harold Harrison Chair in Cardiology Division o Cardiology Department o Medicine Emory University School o Medicine Atlanta, Georgia [130]

Pro essor o Anesthesiology and Medicine University o Wisconsin School o Medicine and Public Health Madison, Wisconsin [153]

O

Stephen D. Clements, Jr., MD

Douglas B. Coursin, MD, FCCP

R

Associate Pro essor o Medicine Division o Gastroenterology &Hepatology Johns Hopkins University Baltimore, Maryland [97]

Assistant Pro essor o Medicine Associate Program Director Grady Memorial Hospital J. Willis Hurst Internal Medicine Residency Program Emory University School o Medicine Atlanta, Georgia [230]

S

John O. Clarke, MD

Dominique L. Cosco, MD, FACP

Yvette M. Cua, MD Associate Pro essor o Medicine Department o Medicine Associate Vice Chair or Clinical A airs Department o Medicine University o Louisville Louisville, Kentucky [28-30, 32]

Randall Czajkowski, MS, RRA, RT(R)(CT) Lead Clinical CT Technologist Brigham and Women’s Hospital Boston, Massachusetts [119]

Sonye K. Danof , MD, PhD Associate Pro essor o Medicine Department o Medicine Division o Pulmonary and Critical Care Medicine Johns Hopkins University School o Medicine Baltimore, Maryland [233]

Jatin K. Dave, MD, MPH Part-Time Instructor, Harvard Medical School Division o Aging, Brigham and Women’s Hospital Boston, Massachusetts Medical Director Geriatrics and Senior Care Options Tu ts Health Plan Watertown, Massachusetts [68, 73]

David B. De Lurgio, MD Pro essor Clinical Cardiac Electrophysiology Emory Saint Joseph’s Hospital Atlanta, Georgia [136]

Steven B. Deitelzweig, MD, MMM, SFHM, FACP Ochsner Health System Medical Director o Regional Business Development System Chairman, Hospital Medicine Associate Pro essor o Medicine-Ochsner Clinical School [24]

xvii

Paul F. Dellaripa, MD

Daniel D. Dressler, MD, MSc, SFHM, FACP

Associate Pro essor Harvard Medical School Division o Rheumatology Brigham and Women’s Hospital Boston, Massachusetts [246]

Pro essor o Medicine Director Internal Medicine Teaching Services Emory University Hospital Associate Program Director J. Willis Hurst Internal Medicine Residency Program Co-Director Semmelweis Society Emory University School o Medicine Atlanta, Georgia [101]

E. Patchen Dellinger, MD

N

O

C

Pro essor and Vice Chair Department o Surgery University o Washington Seattle, Washington [55]

T

Harry A. Demos, MD

S

R

O

T

U

B

I

R

Associate Pro essor Department o Orthopedics Medical University o South Carolina Charleston, South Carolina [65]

Rebecca Dezube, MD Postdoctoral Fellow Johns Hopkins University Pulmonary and Critical Care Medicine Baltimore, Maryland [95]

Lorenzo Di Francesco, MD, FACP, FHM Pro essor o Medicine Division o General Medicine &Geriatrics Program Director J. Willis Hurst Internal Medicine Residency Program Assistant Chie o Medicine, Grady Memorial Hospital Emory University School o Medicine Atlanta, Georgia [93]

Shira Doron, MD, FIDSA Antimicrobial Steward Associate Hospital Epidemiologist Division o Geographic Medicine and In ectious Diseases Tu ts Medical Center Boston, Massachusetts [191]

Michael Dougan, MD, PhD Gastroenterology Fellow Massachusetts General Hospital Boston, Massachusetts [183]

James D. Douketis, MD, FRCP(C), FACP, FCCP Pro essor o Medicine McMaster University Hospitalist Service St. Joseph’s Healthcare Hamilton Hamilton, Ontario, Canada [56, 252]

Aeron A. D. Doyle, MD, CM, FRCPC Assistant Pro essor o Anesthesiology University o British Columbia Department o Anesthesiology, Perioperative Medicine, and Pain Management Providence Health Care Vancouver, British Columbia, Canada [47]

Tracy J. Doyle, MD, MPH Instructor in Medicine Harvard Medical School Pulmonary and Critical Care Medicine Brigham and Women’s Hospital Boston, Massachusetts [85]

xviii

Jacob M. Drew, MD Assistant Pro essor Department o Orthopedics Medical University o South Carolina Charleston, South Carolina [65]

Catherine E. DuBeau, MD Pro essor o Medicine Family Medicine and Community Health, and Obstetrics and Gynecology Clinical Chie o Geriatrics University o Massachusetts Medical School Worcester, Massachusetts [71]

Jenni er Duf , MD Assistant Pro essor o Medicine Division o Hematology and Oncology Department o Medicine University o Florida College o Medicine Hematology and Oncology Section NF/SG Veterans A airs Medical Center Gainesville, Florida [175]

Liam Durcan, MD, FRCPC Assistant Pro essor Department o Neurology and Neurosurgery McGill University Consultant Neurologist McGill University Health Centre Montreal, Quebec, Canada [207]

Kent Russell Edwards, Jr., MD Urology Research Assistant University o South Carolina School o Medicine Columbia, South Carolina [67]

Mikhael F. El-Chami, MD, FACC, FHRS Associate Pro essor o Medicine Division o Cardiology-Section o Electrophysiology Emory University Atlanta, Georgia [134]

Elwaleed A. Elhassan, MD, FACP, FASN Assistant Pro essor o Medicine Division o Nephrology and Hypertension Wayne State University School o Medicine Detroit, Michigan [242]

William J. Elliott, MD, PhD Chair Department o Biomedical Sciences Chie , Division o Pharmacology Pro essor o Preventative Medicine, Internal Medicine, Pharmacology Paci c Northwest University o Health Sciences Yakima, Washington [244]

Joseph C. English, III, MD Pro essor o Dermatology University o Pittsburgh Department o Dermatology Pittsburgh, Pennsylvania [144]

Mary Eno, MD, MPH Regional Chie o Addiction Medicine Southern Cali ornia Permanente Medical Group Los Angeles, Cali ornia [251]

Andrew S. Epstein, MD Assistant Attending Memorial Sloan Kettering Cancer Center Gastrointestinal Oncology Service New York, New York [182]

Evert A. Eriksson, MD, FACS, FCCP Associate Pro essor o Surgery Department o Surgery Medical University o South Carolina Charleston, South Carolina [46]

Samir M. Fakhry, MD, FACS Charles F. Crews Pro essor o Surgery Chie , Division o General Surgery Department o Surgery Medical University o South Carolina Charleston, South Carolina [46]

Matthew E. Falagas, MD, MSc, DSc Adjunct Associate Pro essor o Medicine Tu ts University School o Medicine Boston, Massachusetts Director Al a Institute o Biomedical Sciences Director Department o Internal Medicine and In ectious Diseases Iaso General Hospital Athens, Greece [184]

Kenneth R. Falchuk, MD Associate Clinical Pro essor o Medicine Harvard Medical School Co-Director Inf ammatory Bowel Disease Center Department o Medicine, Division o Gastroenterology Beth Israel Deaconess Medical Center Boston, Massachusetts [164]

Harrison W. Farber, MD Pro essor o Medicine Boston University School o Medicine Director Pulmonary Hypertension Center Boston Medical Center Boston, Massachusetts [237]

C O N T R

Associate Pro essor o Medicine Internal Medicine, Huntsman Cancer Hospital Physician Advisor, Billing Compliance Compliance Services University o Utah Health Sciences Salt Lake City, Utah [31]

Department o Pharmacy Services Brigham and Women’s Hospital Boston, Massachusetts [254]

I

Jeannine Z. Engel, MD

John Fanikos, RPh, MBA

B

CEO/Medical Director Bay Area Hospitalist Associates, Inc. San Francisco, Cali ornia [25]

U

Scott F. Enderby, DO, MMM, SFHM, FACP

T

Chie Cardiovascular Division Pro essor o Medicine John and June B. Hartman Presidential Endowed Chair Executive Director Cardiovascular Service Line University o Utah Health Sciences Center Salt Lake City, Utah [129]

O

Pro essor o Internal Medicine and Medical Microbiology University o Manitoba Director In ection Prevention and Control Unit, Health Sciences Centre Winnipeg, Manitoba, Canada [147, 202]

R

James C. Fang, MD, FACC, FAHA

S

John M. Embil, MD, FRCPC, FACP

Claire E. Farel, MD, MPH Clinical Assistant Pro essor o Medicine University o North Carolina School o Medicine Medical Director UNC In ectious Diseases Clinic UNC Institute or Global Health and In ectious Diseases Chapel Hill, North Carolina [203]

Dimitrios Farmakiotis, MD Assistant Pro essor o Medicine New York University School o Medicine Division o In ectious Diseases and Immunology, NYU Langone Medical Center New York, New York [201]

Jeanne M. Farnan, MD, MHPE Associate Pro essor Section o Hospital Medicine Assistant Dean, Curricular Development and Evaluation Pritzker School o Medicine University o Chicago Chicago, Illinois [13]

Grace Farris, MD Beth Israel Deaconess Medical Center Boston, Massachusetts [168]

Kevin Felner, MD Associate Pro essor Division o Pulmonary and Critical Care New York University School o Medicine Harbor VA Medical Center New York, New York [141]

Andrew Z. Fenves, MD, FACP, FASN Associate Pro essor o Medicine Harvard Medical School Clinician Educator Service Massachusetts General Hospital Boston, Massachusetts [38]

xix

Joseph D. Feuerstein, MD

Michael Gardam, MD, MSc, FRCPC

Assistant Pro essor o Medicine Harvard Medical School Attending in Gastroenterology Center or Inf ammatory Bowel Disease Beth Israel Deaconess Medical Center Boston, Massachusetts [164]

Associate Pro essor o Medicine University o Toronto Director In ection Prevention and Control University Health Network Medical Director Tuberculosis Clinic Toronto Western Hospital Toronto, Ontario, Canada [200]

Joseph J. Fins, MD, MACP

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B

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The E. William Davis, Jr., MD Pro essor o Medical Ethics and Pro essor o Medicine Weill Cornell Medical College Director Medical Ethics and Attending Physician New York Presbyterian Hospital-Weill Cornell Medical Center New York, New York [33]

R

Leslie A. Flores, MHA, SFHM

S

Nelson Flores Hospital Medicine Consultants La Quinta, Cali ornia [26]

John A. Flynn, MD, MBA, MEd, FACP, FACR Medical Director Spondyloarthritis Program Associate Dean and Executive Director Clinical Practice Association Vice President, O ce o Johns Hopkins Physicians Johns Hopkins University Baltimore, Maryland [76]

Ryan M. Ford, MD

Assistant Pro essor o Medicine Johns Hopkins University School o Medicine Department o Medicine Division o Pulmonary and Critical Care Medicine Baltimore, Maryland [233]

Steven Garlow, MD, PhD Associate Pro essor Chie o Psychiatry Emory University Hospital Atlanta, Georgia [223]

Germán E. Giese, MD Assistant Pro essor o Medicine University o Miami Miller School o Medicine Attending, Division o Hospital Medicine University o Miami Hospital Miami, Florida [37]

Assistant Pro essor o Medicine Director o Viral Hepatitis Emory Transplant Center Transplant Hepatologist Emory University Hospital Atlanta, Georgia [159]

Richard S. Gitomer, MD, MBA, FACP

Vance G. Fowler Jr., MD, MHS

Jef rey J. Glasheen, MD, SFHM

Division o In ectious Diseases Duke University Medical Center Durham, North Carolina [189]

Chie Quality O cer University o Colorado Hospital Associate Dean or Clinical A airs, Quality and Sa ety Education Director Institute or Healthcare Quality, Sa ety and E ciency Pro essor Division o General Internal Medicine University o Colorado School o Medicine Aurora, Colorado [59]

Gil Freitas, MD Division o Trauma, Burn, and Surgical Critical Care Harvard Medical School Fellow, Metabolic Support Service Brigham and Women’s Hospital Boston, Massachusetts [42]

Joseph M. Furman, MD, PhD Pro essor Departments o Otolaryngology Neurology, Bioengineering and Physical Therapy University o Pittsburgh School o Medicine Director Divisions o Balance Disorders Pittsburgh, Pennsylvania [84]

Julia M. Gallagher, MD Medical Director MGH Home Based Palliative Care Program Division o Palliative Care Massachusetts General Hospital Boston, Massachusetts [74]

xx

Brian T. Garibaldi, MD

Assistant Pro essor Emory University School o Medicine President and Chie Quality O cer Emory Healthcare Network Atlanta, Georgia [18]

Dragan Golijanin, MD Associate Pro essor o Surgery Director Genitourinary Oncology The Warren Alpert Medical School o Brown University Providence, Rhode Island [180]

Lucas Golub, MD Emory University School o Medicine Atlanta, Georgia [8]

Steven M. Gorbatkin, MD, PhD Associate Pro essor Emory University School o Medicine Nephrologist, Atlanta VA Medical Center Decatur, Georgia [241]

Norman D. Grace, MD

Caroline N. Harada, MD

Lecturer on Medicine Harvard Medical School Pro essor o Medicine Tu ts University School o Medicine Sta Physician Division o Gastroenterology, Hepatology, and Endoscopy Department o Medicine Brigham and Women’s Hospital Boston, Massachusetts [53, 160]

Associate Pro essor o Medicine Assistant Dean or Community-Engaged Scholarship University o Alabama School o Medicine Division o Gerontology, Geriatrics, and Palliative Care Birmingham, Alabama [166]

Charles S. Greenberg, MD Department o Medicine Division o Hematology/Oncology Medical University o South Carolina Charleston, South Carolina [54]

Stephen B. Greenberg, MD, MACP Distinguished Service Pro essor, Herman Brown Teaching Pro essor Baylor College o Medicine Vice Chie o Sta , Chie o Medicine Ben Taub Hospital Houston, Texas [198]

Norton J. Greenberger, MD, MACP Clinical Pro essor o Medicine Harvard Medical School Senior Physician Brigham and Women’s Hospital Boston, Massachusetts [75]

Anne F. Gross, MD Assistant Pro essor o Psychiatry Associate Residency Training Director Oregon Health &Science University Portland, Oregon [229]

Angela S. Guarda, MD Associate Pro essor o Psychiatry and Behavioral Sciences Johns Hopkins School o Medicine Director Eating Disorders Program The Johns Hopkins Hospital Baltimore, Maryland [226]

Navin R. Gupta, MD Department o Medicine Renal Division Brigham and Women’s Hospital Boston, Massachusetts [243]

Sarah P. Hammond, MD Assistant Pro essor o Medicine Harvard Medical School Division o In ectious Diseases Brigham and Women’s Hospital Boston, Massachusetts [204]

C O N T R I B U T

Assistant Pro essor o Surgery Harvard Medical School Division o Trauma, Burn, and Surgical Critical Care Brigham and Women’s Hospital Boston, Massachusetts [45]

O

Joaquim M. Havens, MD

R

Assistant Pro essor Harvard T. H. Chan School o Public Health Division o In ectious Diseases Brigham and Women’s Hospital Boston, Massachusetts [193]

Instructor o Medicine Harvard Medical School Brigham and Women’s Hospital Division o Gastroenterology and Hepatology Boston, Massachusetts [109]

S

Yonatan H. Grad, MD, PhD

Nikroo Hashemi, MD, MPH

Meghan Hayes, MD, FACP Department o Internal Medicine Sutter Medical Group Clinical Instructor University o Cali ornia Davis Medical Center Sacramento, Cali ornia [218, 220]

Catherine P. M. Hayward, MD, PhD, FRCPC Pro essor Pathology and Molecular Medicine/Medicine McMaster University Head, Coagulation Hamilton Regional Laboratory Medicine Program West Hamilton, Ontario, Canada [172]

Galen V. Henderson, MD Director Neurocritical Care and Neuroscience Intensive Care Unit Brigham and Women’s Hospital Assistant Pro essor, Harvard Medical School Boston, Massachusetts [209]

Kathie L. Hermayer, MD, MS, FACE, FACP Pro essor o Medicine Medical Director or Diabetes Management Services at MUSC Division o Endocrinology, Diabetes, and Medical Genetics Medical University o South Carolina Chair, Diabetes Task Force Ralph H. Johnson Veteran’s A airs Medical Center Charleston, South Carolina [52]

Heather Herrington, MD Associate Pro essor o Medicine Division o Gerontology, Geriatrics, and Palliative Care University o Alabama at Birmingham Birmingham, Alabama [166]

Stacy Higgins, MD, FACP Associate Pro essor o Medicine Division o General Medicine and Geriatrics Emory University School o Medicine Atlanta, Georgia [12]

xxi

Keiki Hinami, MD, MS

Jef C. Huf man, MD

Collaborative Research Unit Cook County Health &Hospitals System Chicago, Illinois [41]

Associate Pro essor o Psychiatry Harvard Medical School Medical Director Inpatient Psychiatry Massachusetts General Hospital Boston, Massachusetts [229]

Ashley B. Hink, MD, MPH General Surgery Resident Medical University o South Carolina Department o General Surgery Charleston, South Carolina [63] O

C

Kerstin Hogg, MD, MBChB, MSc

T

U

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Assistant Pro essor Department o Medicine McMaster University East Hamilton, Ontario, Canada [253]

O

Fernando Holguin, MD, MPH

S

R

Associate Pro essor o Medicine and Pediatrics Asthma Institute Division o Pulmonary Allergy and Critical Care Medicine University o Pittsburgh Pittsburgh, Pennsylvania [231]

Anthony N. Hollenberg, MD Pro essor o Medicine Harvard Medical School Chie , Division o Endocrinology, Diabetes, and Metabolism Beth Israel Deaconess Medical Center Boston, Massachusetts [152]

Elizabeth H. Holt, MD, PhD Associate Pro essor Yale School o Medicine Yale Endocrinology Yale Endocrine Oncology Program New Haven, Connecticut [240]

Michael H. Hoskins, MD Assistant Pro essor Clinical Cardiac Electrophysiology Emory University Hospital Atlanta, Georgia [133, 136]

Susy Hota, MD, MSc, FRCPC Assistant Pro essor o Medicine University o Toronto Hospital Epidemiologist and In ectious Diseases Specialist University Health Network Toronto, Ontario, Canada [200]

Liangge Hsu, MD Assistant Pro essor o Radiology Division o Neuroradiology Brigham and Women’s Hospital Harvard Medical School Boston, Massachusetts [118]

Margo S. Hudson, MD Assistant Pro essor o Medicine Harvard Medical School Diabetes Management Service Brigham and Women’s Hospital Boston, Massachusetts [150]

xxii

John T. Huggins, MD Associate Pro essor o Medicine Division o Pulmonary and Critical Care Medical University o South Carolina Charleston, South Carolina [236]

Daniel P. Hunt, MD Pro essor o Medicine Director Emory Division o Hospital Medicine Department o Medicine Emory University School o Medicine Atlanta, Georgia [78]

William R. Hunt, MD Assistant Pro essor o Medicine Division o Pulmonary, Allergy, Critical Care, and Sleep Medicine Department o Medicine Emory-Children’s Center or Cystic Fibrosis McKelvey Lung Transplant Center Emory University School o Medicine Atlanta, Georgia [234]

Aubrey Ingraham, MD Department o Internal Medicine Kaiser Permanente Oakland, Cali ornia [39]

Bertrand L. Jaber, MD, MS Associate Pro essor o Medicine Tu ts University School o Medicine Vice Chair or Clinical A airs Department o Medicine Caritas St. Elizabeth’s Medical Center Boston, Massachusetts [243]

Claire S. Jacobs, MD, PhD Department o Neurology Brigham and Women’s Hospital Boston, Massachusetts [211]

Francine L. Jacobson, MD, MPH Thoracic Radiologist at Brigham and Women’s Hospital Assistant Pro essor Department o Radiology Harvard Medical School Boston, Massachusetts [107, 112-119]

Shilpa H. Jain, MD Clinical Assistant Pro essor (A liated) Division o Endocrinology, Gerontology, and Metabolism Stan ord University School o Medicine Veterans A airs Palo Alto Health Care System Palo Alto, Cali ornia [154]

Kunal Jajoo, MD

Laurence Katznelson, MD

Assistant Pro essor Harvard Medical School Associate Physician Brigham and Women’s Hospital Boston, Massachusetts [158]

Associate Dean o Graduate Medical Education Pro essor o Neurosurgery and Medicine (Endocrinology and Metabolism) Medical Director Pituitary Center Stan ord University School o Medicine Stan ord, Cali ornia [154]

Brent Jewett, MD Clinical Instructor o Surgery Department o Surgery Medical University o South Carolina Charleston, South Carolina [46]

Danielle Jones, MD, FACP Associate Pro essor o Medicine Division o General Medicine and Geriatrics Emory University School o Medicine Atlanta, Georgia [93]

J. Ryan Jordan, MD Cardiovascular Disease and Clinical Cardiac Electrophysiology South Denver Cardiology Associates, PC Littleton, Colorado [135]

S. Andrew Josephson, MD Vice President Neurohospitalist Society Carmen Castro-Franceschi and Gladyne K. Mitchell Distinguished Neurohospitalist Pro essorship Vice Chairman, Parnassus Programs Director, Neurohospitalist Program Department o Neurology University o Cali ornia, San Francisco San Francisco, Cali ornia [104]

Brian W. Kaebnick, MD Structural Cardiology Fellow Department o Cardiology Emory University Hospital Atlanta, Georgia [131]

Stephen P. Kalhorn, MD Assistant Pro essor Neurosurgery Medical University o South Carolina Charleston, South Carolina [64]

Jameela Kari, MD Pediatric Nephrology Unit Department o Pediatrics King Abdulaziz University Jeddah, Kingdom o Saudi Arabia [239]

Assistant Pro essor o Medicine Director Duke Gout and Crystal Arthropathy Clinic Duke University School o Medicine Durham, North Carolina [247]

O N T R I B U T

Robert T. Keenan, MD, MPH

O

Jack Hirsh Pro essorship in Thromboembolism Department o Medicine McMaster University Juravinski Hospital Hamilton, Ontario, Canada [253]

C

Clive Kearon, MB, MRCPI, FRCPC, PhD

R

Pro essor Director Division o Emergency Medicine Pro essor, Department o Neurosciences Vice Chair, Research, Department o Medicine Pro essor, Department o Bioengineering (Adjunct) Clemson University Medical University o South Carolina Charleston, South Carolina [100]

S

Edward C. Jauch, MD, MS

Corey D. Kershaw, MD Associate Pro essor o Medicine Division o Pulmonary &Critical Care Medicine University o Texas Southwestern Medical Center Medical Director, MICU William P. Clements Jr. University Hospital Dallas, Texas [142]

Adeel M. Khan, MD, MPH Taussig Cancer Institute Cleveland Clinic Foundation Cleveland, Ohio [181]

Claude Killu, MD Intensive Care Los Angeles Medical Center Los Angeles, Cali ornia [125]

Emmanuel S. King, MD, FHM, FACP Associate Pro essor o Clinical Medicine Perelman School o Medicine University o Pennsylvania Director o Clinical Operations Section o Hospital Medicine Division o General Internal Medicine Hospital o the University o Pennsylvania Philadelphia, Pennsylvania [21]

Joyce E. King, MD Assistant Pro essor Georgetown University School o Medicine Washington, DC Clinical Instructor University o Maryland Medical School Director Inpatient Medicine Family Medicine Residency Medstar Franklin Square Medical Center Baltimore, Maryland [228]

Emad Kishi, MD Assistant Pro essor o Surgery Division o Abdominal Transplant Department o Surgery Medical University o South Carolina Charleston, South Carolina [66] xxiii

C O N T R I B U

Joshua P. Klein, MD, PhD

Mark S. Lachs, MD, MPH

Associate Pro essor o Neurology and Radiology Harvard Medical School Chie , Division o Hospital Neurology Department o Neurology Brigham and Women’s Hospital Boston, Massachusetts [106]

Irene and Roy Psaty Distinguished Pro essor o Medicine Co-Chie o Geriatrics and Palliative Medicine Weill Cornell Medicine Director o Geriatrics New York Presbyterian Health System New York, New York [167]

Michael Klompas, MD, MPH

Victoria D. Lackey, MD

Associate Pro essor Department o Population Medicine Harvard Medical School Division o In ectious Diseases Brigham and Women’s Hospital Boston, Massachusetts [187]

Duke University School o Medicine Division o Rheumatology and Immunology Duke University Medical Center Durham, North Carolina [249]

O

T

Christopher Knudson, MD

S

R

Instructor o Medicine Division o Hospital Medicine Emory University School o Medicine Atlanta, Georgia [90]

Serena Koenig, MD, MPH Assistant Pro essor Harvard Medical School Division o Global Health Equity Division o In ectious Diseases Brigham and Women’s Hospital Boston, Massachusetts [205]

Sophia Koo, MD Assistant Pro essor o Medicine Harvard Medical School Division o In ectious Diseases Brigham and Women’s Hospital Boston, Massachusetts [201]

Makeida B. Koyi, MD

Harvard Medical School Dana-Farber Cancer Institute Boston, Massachusetts [105]

Albert Q. Lam, MD Associate Physician Division o Renal Medicine Brigham and Women’s Hospital Harvard Medical School Boston, Massachusetts [61]

Lindy H. Landzaat, DO, FAAHPM Assistant Pro essor Division o Palliative Medicine University o Kansas Medical Center Kansas City, Kansas [217]

Vijay H. Lapsia, MD, MBBS Assistant Pro essor o Medicine Mount Sinai School o Medicine New York, New York [238]

Lucia Larson, MD, FACP

Deputy Director o Adult Inpatient Consultation Service Clinical Instructor Community Psychiatry Program Department o Psychiatry and Behavioral Sciences Johns Hopkins Bayview Medical Center Baltimore, Maryland [81]

Associate Pro essor o Medicine Director Division o Obstetric Medicine Women’s Medicine Collaborative The Alpert Medical School o Brown University Providence, Rhode Island [218]

Svetlana Krasnokutsky, MD, MS

Jodi Layton, MD

Assistant Pro essor o Medicine Co-Director NYU Crystal Diseases Study Group New York University School o Medicine New York, New York [247]

Assistant Pro essor o Medicine The Warren Alpert Medical School o Brown University Hematology and Oncology Rhode Island Hospital Comprehensive Cancer Center Providence, Rhode Island [180]

Harold Kudler, MD

Brian Leber, MDCM, FRCPC

Adjunct Associate Pro essor Department o Psychiatry and Behavioral Sciences Duke University Medical Center Durham, North Carolina [224]

Carlos E. Kummer eldt, MD Sta Pulmonologist TJ Samson Community Hospital Glasgow, Kentucky [236]

xxiv

Joshua R. Lakin, MD

Pro essor o Medicine McMaster University Attending Physician Hamilton Health Sciences/Juravinski Hospital and Cancer Centre Hamilton, Ontario, Canada [170]

Noah Lechtzin, MD, MHS, FCCP Assistant Pro essor Director Johns Hopkins Adult Cystic Fibrosis Program Pulmonary Director Johns Hopkins Amyotrophic Lateral Sclerosis Clinic Pulmonary and Critical Care Medicine Johns Hopkins University Baltimore, Maryland [95]

Linda S. Lee, MD

Walter Limehouse, MD, MA, FACEP

Assistant Pro essor o Medicine Harvard Medical School Director Endoscopic Education and Women’s Health in GI Co-Director Pancreas Center Brigham and Women’s Hospital Boston, Massachusetts [161]

Associate Pro essor o Emergency Medicine Medical University o South Carolina Charleston, South Carolina [33]

Blair J. N. Leonard, MD, PhD, FRCP Senior Hematology Fellow McMaster University Hamilton, Ontario, Canada [170]

William I. Levin, MD Associate Pro essor o Medicine Division o General Internal Medicine University o Pittsburgh School o Medicine Pittsburgh, Pennsylvania [60]

Katherine Lewis, MD, MSCR Assistant Pro essor o Medicine and Pediatrics The Medical University o South Carolina Charleston, South Carolina [52]

Cindy Lien, MD Assistant Pro essor o Medicine Harvard Medical School Palliative Care Physician Internal Medicine Hospitalist Beth Israel Deaconess Medical Center Boston, Massachusetts [216]

Elaine Chiewlin Liew, MD, FRCA Assistant Pro essor o Anesthesiology Department o Anesthesiology and Perioperative Medicine David Ge en School o Medicine University o Cali ornia, Los Angeles (UCLA) Ronald Reagan UCLA Medical Center Los Angeles, Cali ornia [153]

C O N T R

Department o Medicine Division o Hematology/Oncology Medical University o South Carolina Charleston, South Carolina [54]

I

Ming Y. Lim, MB BChir

B

Clinical Director Division o Gastroenterology and Hepatology Johns Hopkins University School o Medicine Director o Endoscopy Johns Hopkins Hospital Director Johns Hopkins Integrative Medicine &Digestive Center Lutherville, Maryland [80]

U

Linda A. Lee, MD

T

President Neurohospitalist Society Medical Director EvergreenHealth Neuroscience Institute Clinical Assistant Pro essor University o Washington EvergreenHealth Kirkland, Washington [104]

O

Pulmonary/Critical Care Fellow Emory University School o Medicine Division o Pulmonary, Allergy, Critical Care &Sleep Medicine Atlanta, Georgia [235]

R

David J. Likosky, MD, SFHM, FAHA, FACP

S

Ji Yeon Lee, MD

Lori-Ann Linkins, MD, MSc (Clin Epi), FRCPC Associate Pro essor Department o Medicine Division o Hematology &Thromboembolism McMaster University Juravinski Thromboembolism Service MF1 Director/MF1 Hematology Subunit Planner Michael G. DeGroote School o Medicine Thrombosis &Atherosclerosis Research Institute Hamilton, Ontario, Canada [253]

Ra ael H. Llinas, MD Associate Pro essor o Medicine Associate Pro essor o Neurology Chairman o Neurology Johns Hopkins Bayview Medical Center Baltimore, Maryland [89]

Hermioni N. Lokko, MD, MPP Clinical Fellow o Psychiatry Harvard Medical School Administrative Chie Resident Massachusetts General Hospital Boston, Massachusetts [229]

Lenny López, MD, MPH, MDiv Associate Pro essor o Medicine Chie o Hospital Medicine San Francisco VA Medical Center University o Cali ornia San Francisco, Cali ornia [3]

David J. Lucier, Jr., MD, MBA, MPH Instructor o Medicine Harvard Medical School Director o Quality and Patient Sa ety Hospital Medicine Group Assistant in Medicine Division o General Internal Medicine Massachusetts General Hospital Boston, Massachusetts [15]

xxv

C O N T R I B

Courtney H. Lyder, ND, ScD(Hon), FAAN

Merry Jenni er Markham, MD

Pro essor o Nursing, Geriatric Medicine, and Public Health Dean Emeritus School o Nursing University o Cali ornia Los Angeles, Cali ornia [72]

Associate Pro essor o Medicine Division o Hematology and Oncology Department o Medicine University o Florida College o Medicine Gainesville, Florida [175]

William L. Lyons, MD

Alayne D. Markland, DO, MSc

Pro essor Division o Geriatrics and Gerontology Department o Internal Medicine University o Nebraska Medical Center Omaha, Nebraska [165]

Associate Pro essor o Medicine Division o Gerontology, Geriatrics, and Palliative Care University o Alabama at Birmingham Birmingham, Alabama [71]

Elizabeth H. Mack, MD, MS

Pro essor and Associate Division Director or Critical Care Division o Pulmonary, Allergy, and Critical Care Emory University School o Medicine Director o Research Emory Critical Care Center Section Chie , Grady Memorial Hospital Atlanta, Georgia [142]

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Pediatric Critical Care Medical University o South Carolina Charleston, South Carolina [19]

James H. Maguire, MD, MPH Pro essor o Medicine Harvard Medical School Senior Physician Division o In ectious Diseases Brigham and Women’s Hospital Boston, Massachusetts [205]

Rahul Maheshwari, MD Gastroenterology Fellow Division o Digestive Diseases Emory University School o Medicine Atlanta, Georgia [159]

Scott Manaker, MD, PhD Associate Pro essor o Medicine, Pulmonary, Allergy, and Critical Care Division Vice Chair or Regulatory A airs Department o Medicine Perelman School o Medicine, University o Pennsylvania Philadelphia, Pennsylvania [27]

E rén Manjarrez, MD, SFHM Chie , Division o Hospital Medicine Associate Pro essor o Clinical Medicine Miller School o Medicine University o Miami Miami, Florida [37]

Kimberly D. Manning, MD, FACP, FAAP Associate Pro essor o Medicine Director Distinction in Teaching and Leadership J. Willis Hurst Internal Medicine Residency Program Department o Medicine Division o General Medicine and Geriatrics Emory University School o Medicine Atlanta, Georgia [5]

Michael Manogue, MD Fellow in Cardiovascular Disease Emory University School o Medicine Atlanta, Georgia [133, 135]

Gary Margolias, MD Assistant Pro essor o Anesthesiology Emory University School o Medicine Atlanta, Georgia [139]

xxvi

Greg S. Martin, MD, MSc, FACP, FCCP, FCCM

R. Kirk Mathews, MBA Partner, Schmidt Mathews LLC Providing Executive Search and Leadership Development Services [24]

Melissa Mattison, MD, SFHM, FACP Assistant Pro essor o Medicine Harvard Medical School Chie , Hospital Medicine Unit Massachusetts General Hospital Boston, Massachusetts [168]

Saverio M. Maviglia, MD, MSc Assistant Pro essor o Medicine Harvard Medical School Hospitalist Service Brigham and Women’s Hospital Boston, Massachusetts [22]

Laura K. Max, BA Clinical Research Assistant Johns Hopkins School o Medicine Anesthesiology and Critical Care Medicine Johns Hopkins Hospital Baltimore, Maryland [81]

Matthew W. McCarthy, MD Assistant Pro essor o Medicine Weill Cornell Medicine Assistant Attending Physician NewYork-Presbyterian Hospital New York, New York [33]

Michael McDaniel, MD, FSCAI Assistant Pro essor o Medicine Emory University School o Medicine Director Cardiac Catheterization Lab Grady Health Systems Atlanta, Georgia [128]

Gerard Michael McGorisk, MD, FACC, MRCPI Assistant Pro essor o Medicine Emory University Atlanta, Georgia [132]

Joseph J. Miaskiewicz, Jr., MD, FCCP, SFHM

Deputy Editor or Editorial Projects, UpToDate Boston, Massachusetts [107, 112, 116, 123, 124, e4]

Assistant Clinical Pro essor Tu ts Medical School Chie o Utilization Review and Clinical Documentation Hospitalist North Shore Medical Center Salem, Massachusetts [110, 122]

Graham T. McMahon, MD, MMSc

Chad S. Miller, MD, FACP, FHM

Sylvia C. McKean, MD, SFHM, FACP

Adjunct Pro essor Northwestern University Feinberg School o Medicine President and Chie Executive O cer Accreditation Council or Continuing Medical Education Chicago, Illinois [150]

Julia McNabb-Baltar, MD Instructor o Medicine Harvard Medical School Center or Pancreatic Disease Division o Gastroenterology, Hepatology, and Endoscopy Department o Medicine Brigham and Women’s Hospital Boston, Massachusetts [157]

Thomas E. McNalley, MD Associate Pro essor University o Washington School o Medicine Department o Rehabilitation Medicine Seattle Children’s Hospital University o Washington Medical Center Seattle, Washington [69]

Associate Pro essor Division Director General Internal Medicine Saint Louis University School o Medicine St. Louis, Missouri [92, 94]

Tracey A. Milligan, MD, MS, FAAN Assistant Pro essor o Medicine Harvard Medical School Vice Chair or Education Department o Neurology Brigham and Women’s Hospital Boston, Massachusetts [211]

Elinor Mody, MD Division o Rheumatology Brigham and Women’s Hospital Boston, Massachusetts [127]

Daniel L. Molloy, Jr., MD Division o Cardiology Emory University Atlanta, Georgia [130]

Jakob I. McSparron, MD

Paul A. Monach, MD, PhD

Instructor in Medicine Harvard Medical School Division o Pulmonary, Critical Care, and Sleep Medicine Beth Israel Deaconess Medical Center Boston, Massachusetts [85]

Chie , Rheumatology Section VA Boston Healthcare System Associate Pro essor Section o Rheumatology Boston University School o Medicine Boston, Massachusetts [257]

Niharika D. Mehta, MD Assistant Pro essor o Medicine The Warren Alpert Medical School o Brown University Director o Ambulatory services Division o Obstetric and Consultative Medicine Women and In ants Hospital o Rhode Island Providence, Rhode Island [221]

C

Chie , Division o Rheumatology Pro essor o Medicine and Epidemiology University o Pennsylvania Philadelphia, Pennsylvania [257]

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Associate Pro essor o Surgery Medical University o South Carolina Charleston, South Carolina [66]

N

Peter A. Merkel, MD, MPH

T

John W. McGillicuddy, MD, FACS

R

Fanny L. Pritzker Pro essor o Medicine Economics and Public Policy Chie Section o Hospital Medicine Director, Center or Health and The Social Science The University o Chicago Chicago, Illinois [e2]

I

Technical Specialist Molecular Hematology and Red Cell Disorders Lecturer McMaster University Department o Medicine McMaster University Medical Centre Hamilton, Ontario, Canada [169]

B

David Meltzer, MD, PhD

U

Andrew McFarlane, MLT, ART, FCSMLS(D)

T

Division o Haemostasis and Thrombosis Department o Haematology University Medical Centre Groningen Groningen, The Netherlands [173]

O

Pro essor, Anesthesiology and Pediatrics Chie Sa ety and Risk O cer or Health A airs University o Illinois Chicago, Illinois [20]

R

Karina Meijer, MD, PhD

S

Timothy B. McDonald, MD, JD

Carmen Monzon, MD Clinical Assistant Pro essor o Psychiatry and Human Behavior The Warren Alpert Medical School o Brown University Women’s Behavioral Medicine, Women’s Medicine Collaborative Miriam Hospital Providence, Rhode Island [221]

xxvii

Luis Fernando Mora, MD

Jenni er S. Myers, MD, FACP, FHM

The Arrhythmia Center o South Florida Delray Beach, Florida [134]

Associate Pro essor o Clinical Medicine Department o Medicine Division o General Internal Medicine Section o Hospital Medicine Perelman School o Medicine University o Pennsylvania Philadelphia, Pennsylvania [21]

CoLette Morgan, MD, FHM, CCDS, CDIP

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Assistant Pro essor Division o Hospital Medicine Department o Medicine Emory University School o Medicine Atlanta, Georgia [32]

Christopher Moriates, MD Assistant Clinical Pro essor Division o Hospital Medicine University o Cali ornia at San Francisco Director o Caring Wisely Program UCSF Center or Healthcare Value San Francisco, Cali ornia Director o Implementation Initiatives Costs o Care, Inc. Boston, Massachusetts [2]

Ala Moshiri, MD, PhD Assistant Pro essor o Ophthalmology Eye Center University o Cali ornia, Davis Sacramento, Cali ornia [83]

John E. Moss, MD Assistant Pro essor o Medicine Department o Critical Care Medicine Mayo Clinic Florida Jacksonville, Florida [137]

Srinivasan Mukundan, MD, PhD Associate Pro essor o Radiology Brigham and Women’s Hospital Boston, Massachusetts [113]

L. Silvia Munoz-Price, MD, PhD Associate Pro essor o Clinical Medicine Institute or Health and Society Medical College o Wisconsin Enterprise Epidemiologist Froedtert Health System Milwaukee, Wisconsin [185]

Mandakolathur R. Murali, MD Director o Clinical Immunology Laboratory Massachusetts General Hospital Harvard Medical School Boston, Massachusetts [230]

Ernest Murray, MD Hospital Medicine Section General Internal Medicine and Geriatrics Medical University o South Carolina Charleston, South Carolina [250]

Daniel M. Musher, MD Distinguished Service Pro essor o Medicine Pro essor o Molecular Virology and Microbiology Chie Emeritus, In ectious Disease Section Michael E. DeBakey VA Medical Center Houston, Texas [186]

xxviii

Satish N. Nadig, MD, PhD, FACS Assistant Pro essor Surgery, Microbiology, and Immunology Medical University o South Carolina Transplant Surgery Charleston, South Carolina [66]

Amulya Nagarur, MD Instructor in Medicine Harvard Medical School Hospital Medicine Group Massachusetts General Hospital Boston, Massachusetts [38]

Peter Najjar, MD Resident Department o Surgery Brigham and Women’s Hospital Harvard Medical School Boston, Massachusetts [44]

Dale M. Needham, MD, PhD, FCPA Pro essor Division o Pulmonary &Critical Care Medicine Department o Physical Medicine &Rehabilitation School o Medicine, Johns Hopkins University Baltimore, Maryland [81]

John Nelson, MD, MHM Overlake Medical Center Nelson Flores Hospital Medicine Consultants Bellevue, Washington [24]

Karin J. Neu eld, MD, MPH Clinical Director o Psychiatry Johns Hopkins Bayview Medical Center Associate Pro essor Johns Hopkins University School o Medicine Department o Psychiatry and Behavioral Sciences Baltimore, Maryland [81]

Tobenna Nwizu, MD Taussig Cancer Institute Cleveland Clinic Foundation Cleveland, Ohio [181]

Christopher D. Ochoa, MD Fellow Pulmonary and Critical Care Medicine Emory University School o Medicine Atlanta, Georgia [232]

Victor M. Orellana, MD Department o Medicine Rhode Island Hospital Providence, Rhode Island [174]

Assistant Pro essor o Medicine Sidney Kimmel Medical College Medical Intensive Care Unit Thomas Je erson University Hospital Philadelphia, Pennsylvania [206]

Timothy J. Patton, DO Assistant Pro essor o Dermatology University o Pittsburgh Pittsburgh, Pennsylvania [144]

Menaka Pai, MD, MSc, FRCPC

Jill M. Paulson, MD

Associate Pro essor Department o Medicine Associate Member, Department o Pathology and Molecular Medicine McMaster University Trans usion Medicine Quality Lead and Consultant Laboratory Hematologist Hamilton Regional Laboratory Medicine Program Hamilton, Ontario, Canada [56, 252]

Assistant Pro essor o Endocrinology George Washington University School o Medicine. George Washington Medical Faculty Associates Washington, DC [152]

Sumanta K. Pal, MD Assistant Pro essor and Co-Director Kidney Cancer Program Department o Medical Oncology &Experimental Therapeutics City o Hope Comprehensive Cancer Center Duarte, Cali ornia [179]

Robert M. Palmer, MD Director Glennan Center or Geriatrics and Gerontology Eastern Virginia Medical School Nor olk, Virginia [87]

Anand K. Pandurangi, MD, MBBS, DABPN Pro essor o Psychiatry and Adjunct Pro essor o Radiology Vice Chair, Department o Psychiatry and Chair, Division o Inpatient Psychiatry Virginia Commonwealth University (VCU) Medical Director Inpatient Psychiatry VCU Health System Richmond, Virginia [225]

Jonathan B. Parr, MD, MPH University o North Carolina School o Medicine Division o In ectious Disease Chapel Hill, North Carolina [203]

Jenni er C. Passini, MD Clinical Assistant Pro essor Hospital Medicine University o Wisconsin Department o Medicine Madison, Wisconsin [153]

C O N T

David A. Oxman, MD, FACP

R

Instructor Department o Surgery Director Metabolic Support Service Brigham and Women’s Hospital Division o Trauma, Burn, and Surgical Critical Care Harvard Medical School Boston, Massachusetts [42]

I

Vice President or Medical A airs Chie Medical O cer Duke University Health System Associate Pro essor o Medicine and Pediatrics Duke University School o Medicine Durham, North Carolina [189]

B

Vihas Patel, MD

U

Thomas A. Owens, MD

T

Assistant Pro essor o Medicine Division o Pulmonary and Critical Care Medical University o South Carolina Charleston, South Carolina [236]

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Assistant Pro essor o Medicine Weill Cornell Medical College New York Presbyterian Hospital New York, New York [167]

R

Nicholas J. Pastis, MD

S

Karin Ouchida, MD

Allan B. Peetz, MD Instructor Department o Surgery Brigham and Women’s Hospital Division o Trauma, Burn, and Surgical Critical Care Harvard Medical School Boston, Massachusetts [42-45]

Vincent D. Pellegrini, Jr., MD John A. Siegling Pro essor and Chair Department o Orthopedics Medical University o South Carolina Charleston, South Carolina [65]

Jason Persof , MD, SFHM University o Colorado School o Medicine Hospital Medicine Group Aurora, Colorado [137]

Brent G. Petty, MD The Johns Hopkins Hospital Baltimore, Maryland [9]

Kurt P ei er, MD, FACP, FHM Pro essor o Medicine General Internal Medicine Medical College o Wisconsin Milwaukee, Wisconsin [51]

Tania J. Phillips, MD Pro essor o Dermatology Boston University School o Medicine Boston, Massachusetts [148]

Edward F. Pilkington, III, MD Instructor o Medicine Hospitalist Service Brigham and Women’s Hospital Boston, Massachusetts [189]

xxix

Michael H. Pillinger, MD

Amir A. Qamar, MD

Pro essor o Medicine and Biochemistry and Molecular Pharmacology Co-Director NYU Crystal Diseases Study Group New York University School o Medicine Rheumatology Section Chie VA New York Harbor Health Care System, New York Campus New York, New York [247]

Assistant Pro essor o Medicine Tu ts University School o Medicine Boston, Massachusetts Senior Sta Hepatologist Lahey Hospital and Medical Center Burlington, Massachusetts [53]

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J. Richard Pittman, Jr., MD, FACP

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T

U

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Assistant Pro essor o Medicine Division o General Medicine and Geriatrics Department o Medicine Emory University School o Medicine Atlanta, Georgia [11, 101]

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Carol Pohlig, RN, BSN, CPC

S

Senior Coding and Education Specialist O ce o Clinical Documentation Department o Medicine Hospital o the University o Pennsylvania Philadelphia, Pennsylvania [27]

Timothy J. Poterucha, MD Resident Physician and Clinical Fellow Harvard Medical School Department o Medicine Brigham and Women’s Hospital Boston, Massachusetts [108]

Raymond O. Powrie, MD, FRCP, FACP Pro essor o Obstetrics, Gynecology, and Medicine Alpert School o Medicine o Brown University Chie Medical Quality O cer Care New England SVP or Population Health Chie o Medicine Women &In ants Hospital o Rhode Island Providence, Rhode Island [219]

Michaella Maloney Prasad, MD Assistant Pro essor o Urology and Pediatrics Medical University o South Carolina Charleston, South Carolina [67]

Alicia Privette, MD Assistant Pro essor o Surgery Medical University o South Carolina Department o Surgery Charleston, South Carolina [46]

Alberto Puig, MD, PhD, FACP Associate Pro essor o Medicine Harvard Medical School Director Clinician Educator Service Massachusetts General Hospital Boston, Massachusetts [38]

Rana C. Pullatt, MD, MS, MRCS, FACS, FASMBS Diplomate in Obesity Medicine Associate Pro essor o Surgery Director Robotic Surgery Director Bariatric Surgery VISN-7 Medical University o South Carolina Charleston, South Carolina [63] xxx

Susan Y. Quan, MD [97] Clinical Assistant Pro essor (A liated) Stan ord University School o Medicine Division o Gastroenterology and Hepatology Veterans A airs Palo Alto Healthcare System Palo Alto, Cali ornia

Timothy R. Quinn, MD, CM Medical Director o Dermatopathology Dermpath Diagnostics New England Marlborough, Massachusetts [146]

Talat H. Raja, MD Instructor Hospital Medicine Division o General Internal Medicine and Geriatrics Medical University o South Carolina Charleston, South Carolina [82]

Graham W. Redgrave, MD Assistant Pro essor o Psychiatry and Behavioral Sciences Director or Residency Education Johns Hopkins School o Medicine Assistant Director Eating Disorders Program The Johns Hopkins Hospital Baltimore, Maryland [226]

John J. Reilly, Jr., MD Vice Chancellor or Health A airs Dean or School o Medicine University o Colorado School o Medicine Aurora, Colorado [60]

Kerry Reynolds, MD Instructor in Medicine Harvard Medical School Attending Physician Massachusetts General Hospital Cancer Center Boston, Massachusetts [177, 183]

Joseph Rhatigan, MD Associate Pro essor o Medicine Harvard Medical School Division o Global Health Equity Brigham and Women’s Hospital Boston, Massachusetts [e1]

Jessica Rimsans, PharmD, BCPS Senior Clinical Pharmacist Hemostatic and Antithrombotic Stewardship Pharmacist Brigham and Women’s Hospital Boston, Massachusetts [254]

Tina Rizack, MD, MPH Assistant Pro essor o Medicine and Obstetrics and Gynecology The Warren Alpert Medical School o Brown University Hematology/Oncology Program in Women’s Oncology Women &In ants Hospital Providence, Rhode Island [176]

Thomas P. Rocco, MD Associate Pro essor o Medicine Brigham and Women’s Hospital Boston, Massachusetts [108]

Clare Rock, MD, MS, MRCPI

Assistant Pro essor o Medicine Harvard Medical School Hospitalist Service Brigham and Women’s Hospital Boston, Massachusetts [197, 201, 212]

Sarahi Rodríguez-Pérez, MD

Stephen R. Rotman, MD

Vinayak S. Rohan, MD Department o Surgery Medical University o South Carolina Charleston, South Carolina [66]

Karen L. Roos, MD John and Nancy Nelson Pro essor o Neurology Pro essor o Neurological Surgery Indiana University School o Medicine Indianapolis, Indiana [192]

Alexander E. Ropper, MD Assistant Pro essor Department o Neurosurgery Baylor College o Medicine Houston, Texas [208]

Allan H. Ropper, MD, FRCP Pro essor o Neurology Harvard Medical School Executive Vice Chair o Neurology Brigham and Women’s Hospital Boston, Massachusetts [208, 212]

C O N T

John J. Ross, MD, CM, FIDSA

Department o Medicine Division o In ectious Diseases Johns Hopkins University Baltimore, Maryland [195] Director o Clinical Operations Assistant Pro essor o Clinical Medicine Miller School o Medicine Division o Hospital Medicine University o Miami Hospital Miami, Florida [37]

R

Senior Vice President Vice Chair o Medicine or Quality/Outcomes Division Chie Obstetric Medicine Pro essor o Medicine and Obstetrics and Gynecology The Warren Alpert Medical School at Brown University Providence, Rhode Island [219, 221, 222]

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Karen Rosene -Montella, MD, FACP

B

Assistant Pro essor o Obstetrics and Gynecology Program in Women’s Oncology Department o Obstetrics and Gynecology, Women & In ants’Hospital o Rhode Island The Warren Alpert Medical School o Brown University Providence, Rhode Island [178]

U

Katina Robison, MD

T

Medical Director ISP Hospitalist Service Medical Director Supportive Care Medicine (Palliative Care) Director Care Transitions and Complex Medical Management Associate Pro essor, Cedars-Sinai Medical Center Associate Pro essor, UCLA School o Medicine Cedars-Sinai Health System Los Angeles, Cali ornia [120]

O

Assistant Pro essor o Surgery Harvard Medical School Director Nutrition Support Service Brigham and Women’s Hospital Boston, Massachusetts [58]

R

Bradley T. Rosen, MD, MBA, FHM

S

Malcolm K. Robinson, MD

Gastroenterology Fellow Brigham and Women’s Hospital Boston, Massachusetts [156]

Joseph Rudolph, MD Department o Neurology Cleveland Clinic Cleveland, Ohio [210]

Matthew L. Russell, MD, MSc Medical Director Rehabilitation Service Units Hebrew Rehabilitation Center Hebrew Senior Li e Boston, Massachusetts [73]

Daniel F. Ruthven, MD Clinical Associate o Psychiatry and Behavioral Sciences Johns Hopkins University School o Medicine Baltimore, Maryland [226]

Arturo P. Saavedra, MD, PhD Assistant Pro essor Harvard Medical School Medical Director Medical Dermatology Massachusetts General Hospital Boston, Massachusetts [145]

Michel J. Sabbagh, MD Assistant Pro essor Anesthesia and Perioperative Medicine Medical University o South Carolina Charleston, South Carolina [62]

Cheryl A. Sadow, MD Assistant Pro essor o Radiology Harvard Medical School Division o Abdominal Imaging and Intervention Brigham and Women’s Hospital Boston, Massachusetts [117] xxxi

Bisan A. Salhi, MD, MA

Jef rey L. Schnipper, MD, MPH, FHM

Assistant Pro essor o Emergency Medicine Emory University Department o Emergency Medicine Atlanta, Georgia [121]

Associate Pro essor o Medicine Harvard Medical School Director o Clinical Research, Hospitalist Service Brigham and Women’s Hospital Boston, Massachusetts [40, 151]

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John R. Saltzman, MD, FACP, FACG, FASGE, AGAF Associate Pro essor o Medicine Harvard Medical School Director o Endoscopy Brigham and Women’s Hospital Boston, Massachusetts [156, 162]

Kenneth Sands, MD, MPH

Pro essor Emeritus o Medicine University o Colorado School o Medicine Division o Renal Diseases and Hypertension University o Colorado Hospital Aurora, Colorado [242]

Associate Pro essor o Medicine Harvard Medical School Senior Vice President, Health Care Quality Beth Israel Deaconess Medical Center Boston, Massachusetts [16]

Allison R. Schulman, MD

Milda Saunders, MD, MPH

Associate Pro essor o Medicine Division o Pulmonary, Allergy Critical Care, and Sleep Medicine Emory University School o Medicine Atlanta, Georgia [235]

Assistant Pro essor Section o Hospital Medicine and MacLean Center or Clinical Medical Ethics Department o Medicine University o Chicago Chicago, Illinois [e3]

Marianne E. Savastano, MS, CCC-SLP Speech/Language Pathology Practice Leader Stroke and Spinal Cord Injury Programs Spaulding Rehabilitation Hospital Boston, Massachusetts [70]

Paul E. Sax, MD Pro essor o Medicine Harvard Medical School Brigham and Women’s Hospital Division o In ectious Diseases Boston, Massachusetts [203]

Adam C. Schaf er, MD Instructor in Medicine Harvard Medical School Hospital Medicine Unit Brigham and Women’s Hospital Boston, Massachusetts [35, 111]

Danielle B. Scheurer, MD, MSCR, SFHM Chie Quality O cer and Hospitalist Associate Pro essor o Medicine Medical University o South Carolina Charleston, South Carolina [82, 190]

Lynn Schlanger, MD Associate Pro essor Emory University School o Medicine Atlanta, Georgia [241]

Robert K. Schneider, MD, FACP Associate Pro essor Departments o Psychiatry, Internal Medicine, and Family Medicine Virginia Commonwealth University Director o Mental Health and Primary Care Integration McGuire VA Medical Center Richmond, Virginia [227]

xxxii

Robert W. Schrier, MD, MACP

Gastroenterology Fellow Brigham and Women’s Hospital Boston, Massachusetts [158]

David A. Schulman, MD, MPH, FCCP

Sam Schulman, MD, PhD Thrombosis Service, McMaster Clinic Hamilton Health Sciences-General Hospital Hamilton, Ontario, Canada [173]

Richard M. Schwartzstein, MD Gordon Pro essor o Medicine and Medical Education Harvard Medical School Associate Chie , Division o Pulmonary, Critical Care, and Sleep Medicine Beth Israel Deaconess Medical Center Boston, Massachusetts [85]

Julian L. Sei ter, MD Harvard Medical School Senior Nephrologist and the James Haidas Family Master Clinician Brigham and Women’s Hospital Boston, Massachusetts [61]

Samir K. Shah, MD Division o Vascular Surgery Brigham and Women’s Hospital Boston, Massachusetts [256]

Daniel S. Shapiro, MD Pro essor o Internal Medicine University o Nevada School o Medicine Reno, Nevada [e5]

Ann M. Sheehy, MD, MS Associate Pro essor and Division Head, Hospital Medicine Department o Medicine University o Wisconsin Madison, Wisconsin [153]

Eugenie Shieh, MD Clinical Fellow Johns Hopkins Medicine Division o Gastroenterology Baltimore, Maryland [80]

Deborah M. Siegal, MD, MSc, FRCPC

Scot T. Smith, MD

Division o Hematology and Thromboembolism Department o Medicine McMaster University Hamilton, Ontario, Canada [77]

Chie Medical O cer Sound Physicians Denver, Colorado [25]

Eric M. Siegal, MD, SFHM

Director o Revenue Integrity &Quality University o Utah Healthcare University o Utah School o Medicine Salt Lake City, Utah [31]

Ross D. Silverman, JD, MPH Pro essor o Health Policy and Management Indiana University Richard M. Fairbanks School o Public Health Pro essor o Public Health and Law Indiana University Robert H. McKinney School o Law Indianapolis, Indiana [34]

Christian T. Sinclair, MD, FAAHPM Assistant Pro essor Division o Palliative Medicine University o Kansas Medical Center Kansas City, Kansas [217]

Ajay K. Singh, MBBS, MBA, FRCP Renal Division Brigham and Women’s Hospital Boston, Massachusetts [239]

Anika T. Singh Renal Division Brigham and Women’s Hospital Boston, Massachusetts [239]

Mousumi Sircar, MD Geriatrics Fellow Harvard Medical School Department o Gerontology Beth Israel Deaconess Medical Center Boston, Massachusetts [73]

Gerald W. Smetana, MD, FACP Pro essor o Medicine Harvard Medical School Division o General Medicine and Primary Care Beth Israel Deaconess Medical Center Boston, Massachusetts [51]

Dustin T. Smith, MD Emory University School o Medicine Atlanta, Georgia [8, 10]

Robert L. Smith, MD Associate Pro essor Division o Pulmonary and Critical Care New York University School o Medicine Harbor VA Medical Center New York, New York [141]

Society o Hospital Medicine Key Characteristics Workgroup [24]

C O N T R I B U T O

Lindy Bergman Distinguished Service Pro essor Pro essor, Departments o Medicine and Surgery Director MacLean Center or Clinical Medical Ethics University o Chicago Medical Center Chicago, Illinois [e3]

Pro essor Tu ts University School o Medicine Chie , Division o Geographic Medicine and In ectious Diseases Hospital Epidemiologist Tu ts Medical Center Boston, Massachusetts [191]

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Mark Siegler, MD

David R. Snydman, MD, FACP, FIDSA

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Clinical Associate Pro essor o Medicine (Adjunct) University o Wisconsin School o Medicine and Public Health Medical Director Aurora Critical Care Service Aurora St Luke’s Medical Center Milwaukee, Wisconsin [138]

Diana L. Snow, MA, CCS, CPC, CHC

Members o the Society o Hospital Medicine Key Characteristics Workgroup are Patrick Cawley, MD, Steven Deitelzweig, MD, Leslie Flores, MHA, Joseph Miller, MS, John Nelson, MD, Scott Rissmiller, MD, Laurence Wellikson, MD, and Winthrop Whitcomb, MD

Aaron Sodickson, MD, PhD Associate Pro essor o Radiology Harvard Medical School Section Chie o Emergency Radiology Medical Director o CT Brigham and Women’s Hospital Boston, Massachusetts [113]

Lauge Sokol-Hessner, MD Instructor in Medicine Harvard Medical School Associate Director o Inpatient Quality Attending Hospitalist Beth Israel Deaconess Medical Center Boston, Massachusetts [16]

Margarita Sotelo, MD Associate Clinical Pro essor Divisions o Geriatrics and Hospital Medicine San Francisco General Hospital San Francisco, Cali ornia [165]

Geof rey L. Southmayd, MD Instructor o Medicine Emory University School o Medicine Chie Medical Resident, Emory University Hospital J. Willis Hurst Internal Medicine Residency Program Atlanta, Georgia [102]

Nathan Spell, MD Associate Pro essor o Medicine Emory University School o Medicine Chie Quality O cer Emory University Hospital Atlanta, Georgia [17]

Kelly Cunningham Sponsler, MD, SFHM Assistant Pro essor o Medicine Section o Hospital Medicine Vanderbilt University Medical Center Nashville, Tennessee [14]

xxxiii

Jerry E. Squires, MD, PhD

Ashley Stuckey, MD

Department o Pathology and Laboratory Medicine Medical University o South Carolina Charleston, South Carolina [57]

Assistant Pro essor o Obstetrics and Gynecology Program in Women’s Oncology The Warren Alpert Medical School o Brown University Department o Obstetrics and Gynecology Women &In ants’Hospital o Rhode Island Providence, Rhode Island [178]

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Christopher J. Standaert, MD Clinical Associate Pro essor Rehabilitation Medicine, Neurological Surgery, and Orthopedics and Sports Medicine University o Washington School o Medicine University o Washington Medicine Sports and Spine Physicians Clinic Harborview Medical Center Seattle, Washington [69]

Gerald W. Staton, MD Pro essor o Medicine Division o Pulmonary and Critical Care Medicine Department o Medicine Emory University School o Medicine Atlanta, Georgia [232]

Arlene Stecenko, MD Associate Pro essor o Pediatrics and Medicine Chie , Division o Pulmonary, Allergy and Immunology, Cystic Fibrosis and Sleep Department o Pediatrics Director Emory-Children’s Center or Cystic Fibrosis Associate Director Emory-Children’s Center or Cystic Fibrosis and Airways Disease Research Emory University School o Medicine Atlanta, Georgia [234]

Daniel I. Steinberg, MD Mount Sinai Beth Israel New York, New York [7]

Michael Sterling, MD Assistant Pro essor o Medicine Division o Pulmonary, Allergy and Critical Care Medicine Emory University School o Medicine Atlanta, Georgia [139]

Theodore A. Stern, MD Ned H. Cassem Pro essor o Psychiatry in the eld o Psychosomatic Medicine/Consultation Harvard Medical School Chie , Avery D. Weisman Psychiatry Consultation Service Massachusetts General Hospital Director O ce or Clinical Careers Massachusetts General Hospital Boston, Massachusetts [229]

Melissa B. Stevens, MD Assistant Pro essor o Medicine Division o Hospital Medicine Emory University School o Medicine Atlanta, Georgia Atlanta VA Medical Center Decatur, Georgia [12]

xxxiv

Prem S. Subramanian, MD, PhD Pro essor o Ophthalmology, Neurology, and Neurosurgery Vice Chair or Academic A airs, Department o Ophthalmology University o Colorado School o Medicine Aurora, Colorado [83]

Ram M. Subramanian, MD Associate Pro essor o Medicine and Surgery Hepatology and Critical Care Emory University School o Medicine Atlanta, Georgia [159]

Katelyn W. Sylvester, PharmD, BCPS, CACP Pharmacy Manager Clinical Pharmacy Specialist Brigham and Women’s Hospital Boston, Massachusetts [254]

Jef rey A. Tabas, MD Pro essor o Emergency Medicine Director o Outcomes and Innovations O ce o Continuing Medical Education University o Cali ornia San Francisco School o Medicine San Francisco, Cali ornia [36]

Jenni er K. Tan, MD Associate Physician Northstar Dermatology Fort Worth, Texas [149]

Todd A. Taylor, MD Assistant Pro essor o Emergency Medicine Emory University Atlanta, Georgia [121]

Tracy J. Tipton, MD Urology Resident Medical University o South Carolina Charleston, South Carolina [67]

Catherine Dawson Tobin, MD Assistant Pro essor Anesthesia and Perioperative Medicine Medical University o South Carolina Charleston, South Carolina [62]

Derrick J. Todd, MD, PhD Instructor in Medicine Harvard Medical School Division o Rheumatology Brigham and Women’s Hospital Boston, Massachusetts [246]

David Tong, MD, MPH Assistant Pro essor o Hospital Medicine Department o Medicine Emory University School o Medicine Atlanta, Georgia [234]

Anne C. Travis, MD, MSc

Madeleine Verhovsek, MD, FRCPC

Department o Medicine Division o Gastroenterology, Hepatology and Endoscopy Brigham and Women’s Hospital Boston, Massachusetts [162]

Assistant Pro essor Division o Hematology and Thromboembolism McMaster University Consultant Laboratory Hematologist, Red Cell Disorders Laboratory, Hamilton Regional Laboratory Medicine Program Hamilton, Ontario, Canada [77, 169]

Geof rey Tsaras, MB, ChB, MPH Clinical Assistant Pro essor o Medicine University o Illinois College o Medicine at Rock ord Rock ord, Illinois [194]

Jef rey Turner, MD Assistant Pro essor o Medicine Section o Nephrology Yale University School o Medicine New Haven, Connecticut [245]

Amit Uppal, MD Assistant Program Director Director o MICU Bellevue Hospital Division o Pulmonary, Critical Care, and Sleep Medicine New York University Medical Center New York, New York [140]

W. Alexander Vandergri t, III, MD Associate Pro essor Neurosurgery Medical University o South Carolina Charleston, South Carolina [64]

Joseph Varon, MD, FACP, FCCP, FCCM, FRSM Chie o Critical Care Services University General Hospital Pro essor Department o Acute and Continuing Care University o Texas Health Science Center at Houston Clinical Pro essor o Medicine University o Texas Medical Branch at Galveston Pro essor o Medicine and Surgery UDEM, UNE, UABC, UAT, Anahuac, UACH, USON, UPAEP – Mexico [91]

Alvaro Velasquez, MD Assistant Pro essor o Medicine Division o Critical Care and Respiratory Medicine Emory University School o Medicine Atlanta, Georgia [90]

Nicole F. Velez, MD

Kittane S. Vishnupriya, MBBS Assistant Pro essor o Medicine Johns Hopkins University School o Medicine Baltimore, Maryland [79]

C O N T R I B U T

Department o Medical Microbiology University o Manitoba Winnipeg, Manitoba, Canada [147]

Assistant Pro essor Faculty o Medicine McGill University Division o In ectious Diseases, Department o Medicine McGill University Health Centre Montreal, Quebec, Canada [202]

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Elly Trepman, MD

Donald C. Vinh, MD, FRCPC, FACP

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Eugene Meyer, III Pro essor o Psychiatry and Medicine Departments o Psychiatry and Behavioral Sciences and Internal Medicine Johns Hopkins University School o Medicine Baltimore, Maryland [228]

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Glenn J. Treisman, MD, PhD

Ruth Ann Vleugels, MD, MPH Associate Pro essor o Medicine Harvard Medical School Director Autoimmune Skin Disease Program Department o Dermatology Brigham and Women’s Hospital Boston, Massachusetts [149]

Megan Ann Waldrop, MD Pediatric Neurology Fellow University o Cali ornia, Irvine Children’s Hospital o Orange County Orange, Cali ornia [213]

Ruth H. Walker, MB, ChB, PhD Departments o Neurology James J. Peters Veterans A airs Medical Center, Bronx, NY Mount Sinai School o Medicine New York, New York [210]

Leon Walthall, MD Hospital Medicine Section General Internal Medicine and Geriatrics Medical University o South Carolina Charleston, South Carolina [250]

David A. Walton, MD, MPH Division o Global Health Brigham and Women’s Hospital Boston, Massachusetts [e1]

John Scott Walton, MD Associate Pro essor Anesthesia and Perioperative Medicine Medical University o South Carolina Charleston, South Carolina [62]

Westmoreland Dermatology Associates University o Pittsburgh Medical Center East Pittsburgh, Pennsylvania [145]

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C O N T R I B U T O R S

Annabel Kim Wang, MD

Tosha B. Wetterneck, MD, MS

Associate Pro essor (Neurology) University o Cali ornia, Irvine Orange, Cali ornia Sta Neurologist VA Long Beach Healthcare System Long Beach, Cali ornia [213]

Department o Medicine School o Medicine and Public Health Center or Quality and Productivity Improvement University o Wisconsin Madison Madison, Wisconsin [41]

Sally Wang, MD Instructor Harvard Medical School Hospitalist Brigham and Women’s Hospital Boston, Massachusetts [126]

Assistant Pro essor o Medicine University o Utah School o Medicine Department o Medicine, Cardiology Division, Heart Failure Section University o Utah Health Science Center Salt Lake City, Utah [129]

Martha C. Ward, MD

Christopher M. Whinney, MD, FACP, FHM

Assistant Pro essor Department o Psychiatry and Behavioral Sciences Department o Medicine Society Advisor, Osler Society Assistant Course Director Essentials o Patient Care Course Emory University School o Medicine Atlanta, Georgia [223]

Clinical Assistant Pro essor o Medicine Cleveland Clinic Lerner College o Medicine Chairman, Department o Hospital Medicine Cleveland Clinic Cleveland, Ohio [4]

Theodore E. Warkentin, MD, FRCP(C), FACP, FRCP(Edin) Pro essor Department o Pathology and Molecular Medicine and Department o Medicine Michael G. DeGroote School o Medicine McMaster University Trans usion Medicine, Hamilton Regional Laboratory Medicine Program Service o Clinical Hematology, Hamilton General Hospital Hamilton, Ontario, Canada [171]

Kathryn Webert, MD, MSc, FRCPC Associate Pro essor Department o Pathology and Molecular Medicine McMaster University Medical Director, Utilization Canadian Blood Services Hamilton, Ontario, Canada [172]

Steven Weinberger, MD, FACP Executive Vice President and CEO American College o Physicians Adjunct Pro essor o Medicine University o Pennsylvania Philadelphia, Pennsylvania Senior Lecturer on Medicine Harvard Medical School Boston, Massachusetts [6]

Saul N. Weingart, MD, PhD Chie Medical O cer and Senior VP Medical A airs Tu ts Medical Center Pro essor o Medicine Tu ts University School o Medicine Boston, Massachusetts [15]

Stacy Westerman, MD, MPH Fellow, Cardiovascular Disease Department o Medicine, Division o Cardiology Emory University School o Medicine Atlanta, Georgia [133]

xxxvi

Omar Wever-Pinzon, MD

I. David Wiener, MD Pro essor o Medicine and Physiology and Functional Genomics University o Florida College o Medicine Chie , Nephrology and Hypertension Section Gainesville VA Medical Center Gainesville, Florida [238]

Jef rey G. Wiese, MD, FACP, FSM, SFHM Pro essor o Medicine Tulane University Associate Chairman, Department o Medicine Senior Associate Dean or Graduate Medical Education Director Tulane Internal Medicine Program Tulane University Health Sciences Center New Orleans, Louisiana [92, 94]

B. Robinson Williams, III, MD Assistant Pro essor o Medicine Program Director Cardiovascular Disease Fellowship Emory University School o Medicine Atlanta, Georgia [135]

Neil H. Winawer, MD, SFHM Pro essor o Medicine Emory University School o Medicine Director Hospital Medicine Unit Grady Memorial Hospital Atlanta, Georgia [230]

Eric S. Winer, MD Division o Hematology/Oncology Rhode Island Hospital Providence, Rhode Island [174]

Kristin R. Wise, MD, FHM Assistant Pro essor o Medicine Hospital Medicine Section, General Internal Medicine and Geriatrics Medical University o South Carolina Charleston, South Carolina [250]

Karl D. Wittnebel, MD, MPH

Brian K. Yorkgitis, DO

Medical Director Pre-Operative Pain Program Department o Medicine Cedars-Sinai Medical Center Hospitalist Division o General Internal Medicine Cedars-Sinai Medical Center Los Angeles, Cali ornia [120]

Assistant Pro essor Department o Surgery University o Florida College o Medicine-Jacksonville Jacksonville, Florida [43]

Chie Medical O cer Geisinger Medical Center Director Center or Systems Re-engineering in Healthcare, Geisinger Health System Clinical Pro essor o Medicine Temple University School o Medicine Geisinger Medical Center Danville, Pennsylvania [153]

Rollin Wright, MD

C O N T R I B U T

Associate Pro essor o Medicine University o Pittsburgh Director Internal Medicine Residency Training Program University o Pittsburgh Medical Center Pittsburgh, Pennsylvania [88]

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Kenneth E. Wood, DO, FCCP

Shanta M. Zimmer, MD

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Assistant Pro essor o Medicine Hospital Medicine Section University o Colorado Denver University o Colorado Hospital Aurora, Colorado [59]

Pulmonary and Critical Care Fellow Department o Pulmonary, Critical Care, and Sleep Medicine New York University Medical Center New York, New York [140]

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Brian D. Wol e, MD

Bishoy Zakhary, MD

Camilla Zimmermann, MD, PhD, FRCPC Head, Palliative Care Program University Health Network Director o Research Lederman Palliative Care Centre Princess Margaret Hospital Associate Pro essor o Medicine University o Toronto Toronto, Ontario, Canada [215]

Division o Geriatric Medicine and Gerontology University o Pittsburgh Pittsburgh, Pennsylvania [87]

Irene M. Yeh, MD, MPH Division o Adult Palliative Care Dana-Farber Cancer Institute Brigham and Women’s Hospital Harvard Medical School Boston, Massachusetts [214]

xxxvii

Jatin K. Dave, MD, MPH Part-Time Instructor Harvard Medical School Division o Aging, Brigham and Women’s Hospital Boston, Massachusetts Medical Director Geriatrics and Senior Care Options Tu ts Health Plan Watertown, Massachusetts Part III

Thoracic Radiologist at Brigham and Women’s Hospital Assistant Pro essor Department o Radiology Harvard Medical School Boston, Massachusetts Part V, Section 2

E C T I O N R E V

Francine L. Jacobson, MD, MPH

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Associate Pro essor o Medicine Department o Medicine Associate Vice Chair or Clinical A airs Department o Medicine University o Louisville Louisville, Kentucky Part I, Section 6

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Yvette M. Cua, MD

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Associate Pro essor o Medicine Harvard Medical School Clinical Co-Director, Gynecologic Oncology Director The Oncology Sexual Health Clinic Massachusetts General Hospital Cancer Center Boston, Massachusetts Part VI, Section 7

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Assistant Pro essor o Medicine Division o Hospital Medicine Emory University School o Medicine Atlanta, Georgia Part I, Section 3

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Don S. Dizon, MD, FACP

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Joanna M. Bonsall, MD, PhD

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SECTION REVIEWERS

Tina Rizack, MD, MPH Assistant Pro essor o Medicine and Obstetrics and Gynecology The Warren Alpert Medical School o Brown University Hematology/Oncology Program in Women’s Oncology Women &In ants Hospital Providence, Rhode Island Part VI, Section 7

Steven B. Deitelzweig, MD, MMM, SFHM, FACP

Karen Rosene -Montella, MD, FACP

Ochsner Health System Medical Director o Regional Business Development System Chairman, Hospital Medicine Associate Pro essor o Medicine-Ochsner Clinical School Part I, Section 5

Senior Vice President Women’s Services and Clinical Integration, Li espan Vice Chair o Medicine or Quality/Outcomes Division Chie Obstetric Medicine Pro essor o Medicine and Obstetrics and Gynecology The Warren Alpert Medical School at Brown University Providence, Rhode Island Part VI, Section 12

Dustin T. Smith, MD Emory University School o Medicine Atlanta, Georgia Part I, Section 2

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O R E W O R

important topics in both clinical and nonclinical areas, ranging rom value-based medicine to transplant surgery consultation. The section on billing, coding, and clinical documentation has been greatly expanded, as has coverage o a wide host o malignancies. Because o the importance o the recovery period and transitions to a variety o settings a ter hospital discharge, a welcome new section on rehabilitation and skilled nursing care has also been added. The editors and authors are to be congratulated on again having made a major contribution to the care o hospitalized patients and to those physicians, whether or not they ormally identi y themselves as hospitalists, who care or these patients. Given the breadth and the depth o this text, there are ew questions that clinicians will not be able to answer or guidance that they will not be able to obtain about how to provide the best care or the wide spectrum o their hospitalized patients. Steven E. Weinberger, MD, MACP, FRCP Executive Vice President and Chie Executive O cer American College o Physicians Adjunct Pro essor o Medicine Perelman School o Medicine at the University o Pennsylvania Senior Lecturer on Medicine Harvard Medical School

D

I well remember reading the landmark article by Wachter and Goldman entitled “The emerging role o ‘hospitalists’ in the American health care system,” published in the New England Journal of Medicine in 1996.1 In this article, the authors recognized the need or “a new breed o physicians … specialists in inpatient medicine” and coined the term “hospitalist” to re er to this new type o physician specialist. Since then, the specialty o hospital medicine has become an increasingly popular and success ul career pathway, and has expanded beyond its roots in internal medicine to other disciplines, such as pediatrics, amily practice, and obstetrics. The Society o Hospital Medicine estimated there were approximately 44,000 hospitalists in the United States in 2014, and predicted that number will continue to grow.2 When hospital medicine started, the expertise o hospitalists was ocused on the clinical issues surrounding care o the hospitalized patient. More recently, there has been increasing emphasis on the hospitalist’s role in designing and improving the systems o care in the hospital. These added responsibilities have necessitated an expansion o the hospitalist’s skills set beyond just a clinical knowledge base to an understanding o such topics as teamwork, transitions o care, quality metrics and improvement, and patient sa ety, among many others. A consequence o this proli eration o speci c competencies has been the creation o an optional pathway or internal medicine hospitalists to maintain their certi cation with the American Board o Internal Medicine, o cially re erred to as Focused Practice in Hospital Medicine. In the rst edition o Principles and Practice of Hospital Medicine, McKean and her co-editors took on the herculean task o assembling an outstanding group o contributing authors and putting together a superb, comprehensive textbook o hospital medicine that was published in 2012. In this second edition, the editors have not only updated content but have also added a number o

F

FOREWORD

REFERENCES 1. Wachter RM, Goldman L. The emerging role o “hospitalists” in the American health care system. N Engl J Med. 1996;335:514-517. 2. Bureau o Labor Statistics. http://www.bls.gov/careeroutlook/ 2015/youre-a-what/hospitalist.htm . Accessed April 12, 2016.

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concentrates on what the consulting hospitalist needs to know when consulting on patients undergoing bariatric surgery, neurosurgery, orthopedic surgery, transplant surgery and urologic procedures. All chapters ocus on problems commonly encountered in the hospital setting, such as assessment and management o the diabetic patient, risk assessment and risk reduction or patients with end-stage liver disease, and preoperative assessment o patients with hematologic disorders. Part III: Rehabilitation and Skilled Nursing Care. This new part, written primarily by experts in rehabilitation medicine, provides key in ormation that hospitalists need to consider as they work to ensure sa e transitions rom the inpatient setting to extended care acilities. Individual chapters address rehabilitation options, physical and occupation therapy, common issues such as bowel and bladder incontinence, dysphagia, pressure ulcers, care o surgical wounds and pressure ulcers. The chapter on patient sa ety and quality improvement emphasizes core concepts embraced by hospitalists— the multidisciplinary approach, prevention o complications, and patient-centered communication in the transition o patients to and rom the post-acute setting. The chapter on hospice ocuses on common issues that clinicians need to address as they shi t toward palliative care and consider the best setting or their patients. Part IV: Approach to the Patient at the Bedside. These chapters provide detailed guidance or the initial inpatient evaluation, diagnostic testing, and management o patients with common presenting complaints that may be encountered at the time o admission or in the middle o the night. Each disorder is addressed rom the perspective o hospital care, which in many cases di ers signi cantly rom initial outpatient care or the same complaint. Even experienced clinicians will nd value in reviewing an initial, sometimes algorithmic, approach to common problems such as anemia, alls, delirium, dizziness and vertigo, insomnia, numbness, and weakness (how to localize the problem). Many o the chapters re er to subsequent chapters in Part VI, which covers the diagnosis and management o speci c diagnoses. Part V: Diagnostic Testing and Procedures. E ciency o care, reduced cost, especially length o stay, coupled with high quality begins with clinical problem solving at the time o admission. This part explains how to interpret common admission tests, such as liver biochemical tests or arterial blood gas reports, and how to avoid waste ul, unnecessary medical tests and treatments. The radiology section reviews indications o radiology studies typically ordered in the hospital setting, a general approach to interpretation, patient sa ety issues in imaging and procedures per ormed by interventional radiologists. A comprehensive textbook in hospital medicine would not be complete without a section on procedures. The procedures’ section provides some standardization o procedure per ormance, highlights indications, initial assessment, prevention o complications, and interpretation o results with links to video online resources that provide additional instruction, not possible in a text ormat. This section includes the core set o procedures most likely to be per ormed or supervised by hospitalists and acknowledges local and regional variations in the role o hospitalists per orming or supervising these procedures. Part VI: Clinical Conditions in the Inpatient Setting. Updated clinical content across the breadth o hospital medicine includes major disciplines in internal medicine such as cardiology, gastroenterology,

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Since its initial publication in 2012, Principles and Practice of Hospital Medicine has become established as a leading resource or the specialty o hospital medicine. More than 200 renowned generalists and specialists contributed to make this book comprehensive and authoritative, but as practical as possible. Clinical chapters presented questions that commonly arise in the course o practice and emphasized core concepts with well-illustrated subject matter, radiology, clinical images and quick-view decision trees. The scope o content de ned most o the eld o hospital medicine as it existed in 2012, and the ormat o the text itsel was enhanced both with an online edition available through the widely used AccessMedicine.com, and an app version or use on iPad. Since the publication o the rst edition, the eld o hospital medicine has continued to evolve into areas beyond evidencebased general medical care into the practice o co-management o surgical and medical subspecialties, rehabilitation medicine, and palliative care. Driven by quality improvement e orts, as well as reimbursement models such as bundled payments, the last ew years have seen an increased emphasis on coordination o care between acute care hospitals and other settings, including skilled nursing acilities, rehabilitation acilities, and long-term acute care acilities. The rapid growth o the eld has been accompanied by an emerging cadre o outstanding clinicians and leaders, both at the local, national, and international level, and this book is the product o their collective e orts. The second edition o Principles and Practice of Hospital Medicine provides tools to address the unique set o challenges hospitalists ace in a healthcare system that ought to be sa er and more e ective. It comprehensively covers topics not included in any other print or online textbook. For example, this edition has new sections and chapters on the value and values o hospital medicine; practical, specialty in ormation relating to what consulting hospitalists need to know as they co-manage patients rom other services; key in ormation in rehabilitation and skilled nursing care pertinent to patient sa ety and quality; expanded content on the approach to the patient at the bedside and clinical conditions in the inpatient setting. Using the basic ormat o the rst edition, all content has been updated to incorporate new medical knowledge relevant to the practice o hospital medicine. The second edition has six major parts, covering issues o importance to hospitalists everywhere: Part I: The Specialty of Hospital Medicine and Systems of Care. The authors o this section represent some o the most knowledgeable and orward-thinking people in the areas o value based medicine, critical decision making at the point o care, transitions o care, patient sa ety and quality improvement, practice management, ethics and pro essional development. This part emphasizes the multidisciplinary approach, teamwork, prevention o hospital-acquired complications, and patient-centered communication to ensure sa e and e cient care transitions and hando s. Part II: Medical Consultation. This part explains the traditional role o the medical consultant and updates preoperative cardiac and pulmonary risk assessment and risk reduction. Chapters that ref ect the evolving role o hospitalists in co-management o surgical patients include general principles o surgery and anesthesia, perioperative pain management, and management o common complications in noncardiac surgery. The surgical specialties section

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PREFACE

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and in ectious diseases as well as sections with special relevance to hospital medicine, such as geriatrics, palliative care, psychiatry, toxicology, and addiction. In response to the evolving role o hospitalists on oncology inpatient services, the section covering hematology and oncology has been substantially expanded. Electronic chapters (available on AccessMedicine.com) cover hospital medicine aspects o global health and hospital medicine, the core competencies o hospital medicine, the economics o health care, principles o medical ethics, and bioterrorism. In summary, the second edition o Principles and Practice of Hospital Medicine takes into account how the eld and practice o

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hospital medicine has evolved and the skills required o hospitalists so that they can provide exceptional patient care and clinical care leadership. We thank the American College o Physicians or its collaborative publishing arrangement with McGraw-Hill that included input into the editors, contributors, and overall scope or this new edition. Through its engagement in this book, the college advances it mission to enhance the quality and e ectiveness o health care. Sylvia C. McKean, MD, FACP, SFHM

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Danielle B. Scheurer, MD, MSCR, SFHM

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Daniel D. Dressler, MD, MSc, SFHM, FACP

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John J. Ross, MD, CM, FIDSA

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Sylvia C. McKean, MD, FACP, SFHM, FACP

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including amily and riends. Finally, we wish to recognize physicians who took the time out o their busy schedules to review chapters and/or sections o the book that clearly bene ted rom their valuable expertise.

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The editors o Principles and Practice of Hospital Medicine would like to acknowledge and thank our publisher McGraw-Hill, speci cally, James Shanahan, publisher; Amanda Fielding, editor; Kim Davis, managing editor; Laura Libretti, administrative assistant; Richard Ruzycka, production manager; and the numerous people assisting them to complete this e ort. We also express our gratitude to the many contributors who worked diligently to create a comprehensive resource or our readers and all the people who supported us,

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ACKNOWLEDGMENTS

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PART I The Specialty of Hospital Medicine and Systems of Care SECTION 1

22 The Role of Information Technology in Hospital Quality and Safety . . . . . . . . . . . . . . . . . . . . . . . . . . 134

The Value and Values of Hospital Medicine

1 The Face of Health Care: Emerging Issues for Hospitalists . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5

SECTION 5

Practice Management

3 Racial/Ethnic Disparities in Hospital Care . . . . . . . . . . . . . . . 18

23 Building, Growing and Managing a Hospitalist Practice . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 139

4 Comanagement of Orthopedic Patients

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24 Best Practices in Physician Recruitment and Retention . 150

5 Professionalism in Hospital Medicine . . . . . . . . . . . . . . . . . . 29

25 Teamwork in Leadership and Practice-Based Management . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 157

2 Value-Based Health Care for Hospitalists . . . . . . . . . . . . . . . 10 ...............

6 Principles of Leadership . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33

SECTION 2

Critical Decision Making at the Point of Care

SECTION 6

7 Principles of Evidence-Based Medicine and Quality of Evidence . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 39 8 Diagnostic Reasoning and Decision Making . . . . . . . . . . . . 45 9 Principles of Evidence-Based Prescribing . . . . . . . . . . . . . . . 56 10 Summary Literature: Practice Guidelines and Systematic Reviews . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 62 11 Practical Considerations of Incorporating Evidence into Clinical Practice . . . . . . . . . . . . . . . . . . . . . . . . 70

SECTION 3

27 Professional Coding and Billing Guidelines for Clinical Documentation . . . . . . . . . . . . . . . . . . . . . . . . . . 173 28 Consultation, Comanagement, Time-Based, and Palliative Care Billing . . . . . . . . . . . . . . . . . . . . . . . . . . . . 182 29 Billing for Procedures and Use of Modifiers in Inpatient Practice . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 192 30 Billing in the Teaching Setting and Billing with Advanced Practice Providers . . . . . . . . . . . . . . . . . . . . 198 32 Taming the ICD-10 Monster

12 Care Transitions into the Hospital: Health Care Centers, Emergency Department, Outside Hospital Transfers . . . . . . . . . . . . . . . . . . . . . . . . . . . . 79 .....

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14 Care Transitions at Hospital Discharge . . . . . . . . . . . . . . . . . 90

SECTION 4

Billing, Coding, and Clinical Documentation

31 Hospital-Driven Documentation

Transitions of Care

13 Care Transitions within the Hospital: The Hand-Off

26 Negotiation and Conflict Resolution . . . . . . . . . . . . . . . . . . 164

Patient Safety and Quality Improvement

15 Principles of Patient Safety: Intentional Design and Culture . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 99 16 Patient-Centered Care . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 104 17 Harnessing Data to Make Quality Improvement Decisions: Measurement and Measures . . . . . . . . . . . . . . . 110 18 Standardization and Reliability . . . . . . . . . . . . . . . . . . . . . . . 113 19 Tools to Identify Problems and Reduce Risks . . . . . . . . . . 118

SECTION 7

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Principles of Medical Ethics and Medical-Legal Concepts

33 Common Indications for Ethics Consultation

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34 Medical-Legal Concepts: Advance Directives and Surrogate Decision Making . . . . . . . . . . . . . . . . . . . . . . 224 35 Medical Malpractice . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 231

SECTION 8

Professional Development

36 Principles of Adult Learning and Continuing Medical Education . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 243 37 Cultural Competence

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38 Career Design and Development in Academic and Community Settings . . . . . . . . . . . . . . . . . . . . . . . . . . . . 253

20 Preventing and Managing Adverse Patient Events: Patient Safety and the Hospitalist . . . . . . . . . . . . . 124

39 Mentorship of Peers and Trainees . . . . . . . . . . . . . . . . . . . . 257

21 Principles and Models of Quality Improvement: Plan-Do-Study-Act . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 130

41 For Individuals and Practices: Career Sustainability and Avoiding Burnout

40 Research in the Hospital . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 264 .................

273 1

SECTION 1 The Value and Values of Hospital Medicine

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CHAP TER

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The Face of Health Care: Emerging Issues for Hospitalists Patrick J. Cawley, MD, MHM

INTRODUCTION Hospital medicine is entering its third decade since the term “hospitalist” was rst created by Wachter and Goldman. There are now approximately 40,000 hospitalists and the number is likely to reach 50,000 in the next decade. The specialty has emerged rom vigorous early debate about whether there was su cient evidence to justi y the role o hospitalists to a point where hospital medicine programs are hard-wired and indispensable in the majority o US hospitals. Early leaders and pioneers in hospital medicine were requently two to three physician programs with heavy call burdens. Current hospital medicine groups, particularly in larger hospitals, average approximately 15 clinicians and have complicated alternating schedules with clear time o . Early hospitalists o ten served in hospital leadership roles with no dedicated time. They were o ten the only source o quality and sa ety leadership across the hospital. Today, hospitalists requently have committed time to serve in quality and sa ety positions as well as other medical leadership roles. Most hospitals now have numerous sta that oversee various quality unctions and ably assist these hospitalist leaders. While some aspects have greatly advanced or hospital medicine, two things have not changed: • Pressure to care or sick patients requiring hospitalization—In many

hospitals, the severity o illness across the patients cared or by hospitalists continues to rise. The number o patients covered by hospitalists grows in most hospitals and it is not unheard o or all medical inpatients to be cared or by hospitalists. • Juggling time between clinical care and hospital leadership— While there are greater numbers o hospitalists and more hospital sta ocused on quality and sa ety, the need or clinician leadership has never been more necessary. The vacuum caused by physicians no longer seeking hospital sta privileges as well as the overall urgent need or a new paradigm in health care to increase quality and decrease the cost o care has only resulted in greater need or hospitalists and physician leadership. Hospitalists are quickly expected to assume ormal leader roles as well as clinical team leaders. The need or inpatient care will not go away but how we care or the acutely ill may change. The demand or physician leadership does not diminish, but our ocus on certain issues will vary. So what are the issues acing hospitalists in the next decade? Based on care ul study o patients, amilies, hospitalists, hospitals, and health systems, we can predict the likely emerging issues. “VALUE” Similar to history, certain issues in health care predominate during a particular era because o timing related to unique discovery, emerging evidence, or simply greater knowledge by the masses o a problem. In the late 1990s, quality began its emergence as the principal concern in health care. This started in the 1980s with early studies examining inconsistency and errors as well as problems associated with overuse, misuse, and underuse o health care services. The Institute o Medicine released reports about the quality o health care in the United States in 1994, 1999, and 2001. Each o these had a slightly di erent ocus, and over the next decade, improving quality became a common theme in health care. American hospitals, health systems, and clinicians responded, albeit slowly and deliberately, but by 2010, no area o medicine had ailed to grasp the undamentals o the quality movement and make changes or the better. During this same decade, another concept gained 5

ve organizing characteristics that need to guide the thinking o people in a high-reliable organization: • Preoccupation with ailure—Everyone in the organization is

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broad consensus—improved quality is usually less expensive. This rst began as outcomes that were seen alongside quality improvement, but steadily it became clearer and today there is wide spread evidence that quality and cost are closely interconnected. The best quality is o ten the least expensive. As the linkage grew, the ocus on value in clinical care emerged to a signi cant degree among the large numbers o leaders in health care. The value equation (value = quality/cost) in health care is certainly not new. One can go back decades and read numerous re erences in the health care literature. There have been many proposed versions o the value equation depending largely on how one de nes quality. The early concept o value was mainly in re erence to the health care system and the overall approach to strategically improving health care. Today, a ter almost two decades o quality improvement along with the more recently acceptance o cost containment as an independent quality measure, the concept o value is rapidly approaching majority acceptance by physicians and health care leaders. The next decade will see value broadly and deeply pushed into the health care system. Forward thinking hospitalists and hospital medicine groups will be ready or the emergence o value as an outcome by which they will be measured.

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PRACTICE POINT Hospitalists, by virtue o their unique role in the health care system, will be expected to embrace the concept o value (value = quality/cost) and drive its use into everyday clinical practice. Quality is de ned as sa e, e ective, e cient, equitable, patient centered, and timely care. Cost is de ned as the unit cost o care delivery by the hospitalists. Each o these should be de ned, measured, and incrementally improved by the hospital medicine team.

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These organizing processes are essential to the development o a highly reliable organization and all leaders and physicians in an organization attempting to achieve high reliability should understand the theory and application o each characteristic.

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• HIGH RELIABILITY As quality and sa ety improvement has been embraced by health care, it has become abundantly clear that more radical trans ormation is necessary in order to accomplish a greater magnitude o error reduction and quality consistency. This need or trans ormation led health care to an examination o how other industries such as nuclear power and aviation have achieved a higher degree o reliability resulting in sa ety improvement and avoidance o potentially catastrophic events. Subsequent research revealed that success ul organizations in high-risk industries achieve high reliability by maintaining a cultural mind ulness that allows them to continually reinvent themselves in the ace o highly complex environments. As high-reliability organizations (HRO) were studied, it became clear that there are common challenges across organizations pursuing high reliability: • Hypercomplex environment • Tight coupling teams where members depend on tasks per• • • •

ormed across their team Extreme hierarchical di erentiation Multiple decision makers in a complex communication network Need or requent, immediate eedback Compressed time constraints

Many o these challenges exist in hospitals, and as a result the concept o high-reliability organizations in health care has been broadly embraced as potentially the trans orming approach needed to vastly improve quality and sa ety. As health care incorporates the methodology o HRO, it is important to study the work o Weick and Sutcli e who have identi ed 6

ocused on errors and near-misses in order to learn rom them and gure out how to prevent recurrence. Finding and xing problems is everyone’s responsibility. Leaders support and encourage this approach. Reluctance to simpli y interpretations—Everyone in the organization is driven to ask why something happens and do not rely on the rst or easiest explanation. Sensitivity to operations—Everyone in the organization is ocused on ways their work processes might break down and are then encouraged to share potential ailures and create best practices. Situational awareness is part o the organizational culture. Commitment to resilience—Everyone in the organization works quickly to contain errors that do occur in order to minimize potential harm. Additionally, errors do not disable the organization. The organization responds robustly and looks or new solutions to prevent catastrophes. De erence to expertise—Everyone in the organization listens to people who have the most developed knowledge o the task at hand and empowers them to make decisions in order to quickly mitigate harm. Sometimes, those individuals might not have the most seniority, but they are still encouraged to voice their concerns, ideas, and input—regardless o hierarchy.

Hospitalists are key to the development o an HRO because o their central role in hospital operations. Hospitals on the HRO journey will rely heavily on hospitalists to success ully navigate the process. Hospitalists should study the science o high reliability as it holds great promise to trans orm hospital medicine and health care in general.

PATIENT-CENTERED CARE/CONSUMERISM The word “consumer” turns o many physicians, but the movement cannot be underestimated in how it is changing health care. The most strident opponents to the word requently become some o the most vocal advocates or a more patient-centric approach when they become users o the health care system. The history o patient-centered care can be directly traced to the civil and human rights activism in the 1960s. In 1978, Angelica Thieriot started the Planetree organization a ter a series o upsetting personal health care experiences. The organization “vowed to reclaim or patients the holistic, patient-centered ocus that medicine had lost.” Harvey Picker ounded the Picker Institute in 1986 or similar reasons and then teamed up with the Commonwealth Fund to research a patient-centric approach. The term “patient centered” was coined and then later changed to “patient and amily centered” by the Institute or Family Centered Care which was ounded in 1992, subsequently becoming the Institute or Patient and Family Centered Care in 2010. Through the Picker/Commonwealth Fund research, we began to see di erences in what patients noted as important versus physicians. Surveying patients about patient experience with the health care system started. This led to the Institute o Medicine emphasizing the concept o patient-centered care in its reports on quality care in the United States. Patient-centered care was de ned as providing care that is respect ul o and responsive to

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Hospitalists should embrace the concepts o patient-centered care, patient satis action, and patient engagement. Each o these concepts overlaps, yet di ers in meaning ul ways and should be used in the right context.

TRANSITIONS OF CARE Since the dawn o hospital medicine, there has been a ocus on care transitions, which are the movement patients make between health care practitioners during the course o a chronic or acute illness. Early in the hospital medicine movement, this time period was o ten re erred to as the “voltage drop.” Because o the discontinuity introduced when a patient’s outpatient physician is di erent than their inpatient physician, the importance o care transition in terms o patient quality and sa ety is paramount. One o the pro essional organizations o hospital medicine, the Society o Hospital Medicine, was an early adopter in promulgating the study o transitions and the determination o best practices by hospitalists and hospitals. Many potential models have been developed to improve hospital to home transitions including BOOST, Care Transition Intervention, Project Red, and the Naylor Model. Health care payers are developing nancial incentives or hospitalists as well primary care physicians to ocus on care transitions. The wider use o electronic health records (EHR) by physicians and hospitals holds great promise as a tactic to

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improve in ormation trans er as patients move between providers. However, EHR issues such as how in ormation is displayed as well as the lack o linkage between di erent EHR systems limit the e ectiveness o EHRs in ully improving the knowledge “voltage drop.” In the last several years, the ocus on thirty-day hospital readmission rates has become a signi cant driver o the emphasis on care transitions. This is largely driven by the Centers or Medicare and Medicaid penalties to hospitals with poor per ormance e ective October 1, 2012. Readmission rates are seen as a potential outcome measure or poor care transitioning. There is increasing evidence that socioeconomic actors play a large role in determining readmission rates, so one should be care in completely linking readmission rates to poor transition e orts by hospitals and hospitalists. As the link to socioeconomic actors is urther understood, this will likely require hospitals and health systems to work closely with community programs and governments to address these actors i more trans ormative improvement is to be made in readmission rates.

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Health care will remain ragmented, but the advent o electronic health records and ormal transition o care programs o er potential or lessening the dangers to patients during this time. All hospitalists and hospital medicine groups should have an active transition o care program.

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Telehealth is a broad term used to re er to the process o providing health care services at a distance. It is increasingly per ormed via synchronous or asynchronous video connection. Telemedicine is a component o telehealth and re ers to the delivery o clinical services to patients in other locations. Examples o telemedicine include video consultations with physicians, digital transmission o medical imaging, and remote monitoring o intensive care unit patients. The delivery o clinical care via video is rapidly improving. Early issues such as network availability, capability, and delivery cost continue to progress on an annual basis. Open, secure so tware plat orms are replacing closed proprietary systems. This brings in an era o ease o use as well as signi cant cost decrease. Patients are increasingly accepting telehealth visits. The growing use o smartphones and tablets by patients and amilies present a potential platorm or the provision o enhanced communication and clinical care. Regulators o the practice o medicine such as state boards o medicine have been slow to ully accept and grant unrestricted licensure, but public demands or telehealth are likely to pressure regulators to relax constraints. Similarly, 2015 was a landmark year or telemedicine in that over hal o the states now require health plans to cover and reimburse or telemedicine in the same manner and at the same rate as in-person services. Telehealth parity in the remaining states or via ederal mandate is only a matter o time. Provider acceptance has been limited at rst and mainly related to early adopters and innovators trialing new methods and systems. As telehealth visits have increased, the need or more dedicated provider time and systems to schedule, record, and ollow-up visits has increased.

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individual patient pre erences, needs, and values and ensuring that patient values guide all clinical decisions. In addition to patient-centered care, two additional notions are important to understand. Both are subsets o patient-centered care, which as an expression has come to mean a lot o di erent things, and it is important to di erentiate. Patient experience is the sum o all interactions, shaped by an organization’s culture, that inf uence patient perceptions across a continuum o care. It is measured by patient surveys. For hospitalists, the most requent measurement method is the HCAHPS (Hospital Consumer Assessment o Healthcare Providers and Systems) survey which is used or adult inpatients and measures patients perceptions about communication with nurses, communication about medicines, communication with doctors, pain management, cleanliness and quietness o the hospital environment, responsiveness o hospital sta , discharge in ormation, and the overall rating o the hospital. Patient experience and satis action surveys are common to all hospitals and are important as a method o understanding the patient viewpoint. They are used as quality measure to be continuously improved, but they are only one element o patient-centered care and should be understood as that. Patient engagement are actions taken by individuals to obtain the greatest bene t rom the health care services available to them. Patient engagement occurs when patients eel empowered to move to a state o active participation and sel -e cacy in managing their health. This does not mean just obeying directives rom health care providers, but rather moving to a higher plain o involvement, interest, and sel -awareness. Why is patient engagement so important? Engaged patients have better health outcomes, incur less costs, and enjoy greatest value (quality/cost) rom health care system. A patient can conceivably be satis ed with their health care experience while having minimal engagement. In order to optimize patient engagement, there are key patient concepts to understand and incorporate into the health care experience such as literacy level, readiness to learn, readiness to change, learning style, and patient activation.

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Telehealth is rapidly growing and likely to impact the practice o hospital medicine over the next decade in many potential ways. Examples include the care o patients by hospitalists remotely, enhanced availability o specialists in many hospitals, and tele-critical care monitoring. 7

TRANSPARENCY

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There are multiple major approaches to improving quality and sa ety in health including adherence to a quality improvement methodology, outcomes transparency or public reporting, nancial incentives, regulation or accreditation, and competition. Outcomes transparency is the one which most physicians and organizations have the least expertise, but it is very high on the list o importance or patients and amilies. There is not a long history o transparency in health care and one o the earliest was the publication o hospital mortality rates and outliers by the Healthcare Financing Administration (HCFA) in the 1980s. This resulted in backlash rom hospital executives who when surveyed overwhelmingly ound the data o little use. Since then, there has been persistent and increasing outcomes transparency including severity adjusted mortality rates or coronary artery bypass gra ts survey in New York and Pennsylvania in the late 1980s and early 1990s, and National Committee or Quality Assurance reporting in 1993 o managed care plans and Healthcare E ectiveness Data and In ormation Set (HEDIS) indicators. In 2002, the Joint Commission began reporting outcomes and the National Quality Foundation developed the serious reportable events classi cation. By the mid-2000, many companies such as HealthGrades and Consumer Report as well as multiple states were releasing a variety o health care outcome reports on a regular basis. Price transparency in health care also began to rise. In 2006, President Bush signed a Transparency Executive Order, which urther opened avenues or pricing and quality transparency. In 2015, the Robert Wood Johnson Foundation held its second transparency summit with the ollowing conclusions:

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1. Transparency may not be ubiquitous, but it is now a permanent eature o the health care landscape. 2. For all the progress made in transparency, there is much more work to be done. 3. There is a paradox: The more transparency we have in health care, the more we expose how little we actually know or understand. Health care transparency is part o a larger transparency trend due to the rise in global market economics and its resultant demand or data, an increase in communication technology which acilities transparency, and an “internet culture” which demands a more open interaction. Health care transparency is clearly growing and not a ad. The OpenNotes project, in which patients are able to see their doctors’visit notes, ound that patients become more engaged with such access. This is likely to become routine in the near uture. While transparency in health care is largely viewed positively, or patients to achieve optimal engagement rom transparency will require better design principles into public reports.

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Hospitalist and hospital medicine group should prepare or greater transparency and expect probable ull access by patients and amilies in the uture to the medical record as well as quality and pricing data. We should not underestimate the patients and amilies ability to assimilate the in ormation in public transparency reports!

GENOMICS/GENETICS The past two decades has birthed a dizzying array o genomic technologies that ranges rom rapid genome sequencing to the ability to evaluate genomes across large populations to the discovery o genetic basis o certain diseases as well drug responsiveness. The combination o these genomic technologies is resulting in new types o genetic testing which will increasingly result in clinical 8

relevance. In addition, genetic tests are now directly marketing to the consumer who comes to the physician seeking additional knowledge. The combination o genomic technologies and the electronic health record holds great promise or medical care to become more precise and individualized, however many record systems are o ten lacking core data to optimize this connection. To ully permeate these technologies into medical care, health care leaders and physicians must ensure that electronic health records are built to obtain appropriate in ormation, such as demographics, medications, diagnosis, vital signs, and other in ormation. Pioneers o learning health care systems have established streamlined consenting processes and data warehouses. However, systems are not consistently incentivized to build these capacities. Health leaders want evidence be ore investing resources, yet without those investments such evidence is hard to gather.

PRACTICE POINT

• •

Hospitalists should prepare or the coming clinical relevance in genetic testing, particularly in the patient’s individual potential response to drug therapy. Hospitalist leaders should work with their hospital in ormation technology team to ensure that the hospital electronic health record is optimized to link genomic and patient in ormation.

TEAMWORK TRANSFORMATION The acceptance and rapid growth o hospitalists, based on personal observation, in many hospitals and health systems is tied to the team approach by early hospitalists. These hospitalists were available to hospital personnel to a great degree than nonhospitalists and this o ten resulted in close relationships and greater teamwork. Studies o nursing satis action showed higher results in hospitals with hospitalists. Today, many hospitalist leaders have typically been trained in the mechanics o teamwork and advocate or greater interaction and voice across the hospital medicine team. The ocus on value in the coming decade will orce a reexamination o the hospital medicine team. The typical hospitalist is likely to assume the care o much greater numbers o patients on a daily basis and this will only be achieved through a trans ormation o the hospital medicine team. To alter the present system will require rst and oremost a willingness o both hospitalists and hospital leaders to modi y it. This is not an easy task as signi cant change management skills are required as well as a commitment to a higher level o team reliance, communication, and trust. There will need to be a diligent ocus on patient satis action, each team member’s satis action, and clinical outcomes. It can be achieved aster i there is payer f exibility in pro essional and hospital reimbursement.

PRACTICE POINT

•

Hospitalists should continue to ocus on teamwork and continue to advocate or an interpro essional multidisciplinary approach. Forward thinking hospitalists should trial the use o nonphysician providers, such as nurses, pharmacists, advanced practice providers, nutritionists, and others in innovative ways in order to achieve greater value to the patients.

HOSPITALIST/PHYSICIAN STRESS The health care system is undergoing tremendous change and because o the central role in the health care system physicians will experience signi cant change. In addition, there are pro essional

LEADERSHIP The need or hospital medicine leadership has never been greater. It was there at the dawn o hospital medicine and it will not wane in the coming years. The demand spans rom clinical team leadership to program leadership to hospital and health system senior executive levels. I you have been a user o the health care system, you understand the need immediately. We can do great things in medicine, but it can be undone by some o the most trivial issues. To recti y this, particularly in the hospital setting, requires ocus and leadership as well as the right emotional commitment by hospitalists. William Welch, the rst dean o the Johns Hopkins School o Medicine, said it eloquently in his re erence to a new approach to medical training—”I can think o but one motive which might in uence you to come here with us and that is …our ideals and our uture…This will not appeal to the great mass o the public, not even to the medical public, or a considerable time. What we shall consider success, the mass o doctors will not consider a success.” As hospitalists, we should keep the patient in our ocus at all times and continue to lead the trans ormation in quality and sa ety across health care.

C H A P T E R 1

SUGGESTED READINGS

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Berwick DM, Wald DL. Hospital leaders’ opinions o the HCFA mortality data. JAMA. 1990;263(2):247-249.

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Cawley PJ, Deitelzweig S, Flores L, et al. The key principles and characteristics o an e ective hospital medicine group: an assessment guide or hospitals and hospitalists. J Hosp Med. 2014;9:123-128.

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Coleman EA. Falling through the cracks: challenges and opportunities or improving transitional care or persons with continuous complex care needs. J Am Geriatr Soc. 2003;51(4):549-555.

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Hansen LO, Greenwald JL, Budnitz T, et al. Project BOOST: e ectiveness o a multihospital e ort to reduce rehospitalization. J Hosp Med. 2013;8:421-427.

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Institute o Medicine. America’s Health in Transition: Protecting and Improving Quality. Washington, DC: National Academies Press; 1994.

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Institute o Medicine. Crossing the Quality Chasm: A New Health System or the 21st Century. Washington, DC: National Academy Press; 2001.

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Institute o Medicine. To Err Is Human: Building a Sa er Health System. Washington, DC: National Academy Press; 1999.

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Jack BW, Chetty VK, Anthony D, et al. A reengineered hospital discharge program to decrease rehospitalization: a randomized trial. Ann Intern Med. 2009;150(3):178-187.

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Naylor MD, Aiken H, Kurtzman ET, Olds DM, Hirschman KB. The importance o transitional care in achieving health re orm. Health Af (Millwood). 2011;30(4):746-754.

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All hospitalists should be aware o high burnout and pro essional dissatis action potential and understand the signs and symptoms in order to appropriately intervene to treat physician distress. Hospital medicine group leaders need to activity manage high physician stress levels and institute physician wellness programs.

Hospitalists and hospital medicine groups should ocus on ensuring high unctioning leadership and leadership succession planning within the hospital medicine group at all times. Hospital medicine groups can enhance their e ectiveness and should implement high-per ormance strategy.

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reimbursement challenges, increased scrutiny in terms o quality outcomes, cultural transparency, and increasing demands or physician time and presence. Incorporating new electronic health records into the daily work o physicians requires retraining and optimization. Medical knowledge and techniques advance requiring constant relearning. Administrative burdens related to reimbursement continue to rise. There are simply many pressure points on the individual physician. For hospitalists, who interact with patients and amilies at a very stress ul time—acute illness requiring hospitalization, this can lead to tense and demanding interactions and communications. On the leadership side, there is pressure or hospitals to deliver greater value and all hospital leaders, including hospitalists, will experience great demands to develop and lead innovations. The list o stress points seems endless and overwhelming on the individual hospitalist. However, the ability to positively impact patients and amilies has never been greater in the history o medicine. Hospitalists should recognize that despite the numerous stressors as well as ambiguity o the uture, the ability to help patients and amilies is tremendously satis ying and pro essionally ul lling. Pro essional dissatis action and burnout is treatable i recognized and managed appropriately. There are personal and organizational approaches to prevent physician distress as well as optimize physical, emotional, and psychological wellness. Hospitalists and particularly hospital medicine leaders should ully understand the signs and symptoms o distress and have options or re erral.

Roberts KH, Rousseau DM. Research in nearly ailure- ree, highreliability organizations: having the bubble. IEEE Trans Eng Manage. 1989;36(2):132-139. Wachter RM, Goldman L. The emerging role o “hospitalists” in the American health care system. N Engl J Med. 1996;335:514-517. Weick KE, Sutcli e KM. Managing the Unexpected: Assuring High Per ormance in an Age o Complexity. San Francisco, CA: Jossey-Bass; 2001. Wol JA, Niederhauser V, Marshburn D, LaVela SL. De ning patient experience. Patient Exp J. 2014;1:7-19. ONLINE RESOURCES Center or Advancing Health. 2010. A New De nition o Patient Engagement: What Is Engagement and Why Is It Important. http :/ / www.c ah.org / p d s/ CFAH_En g ag e m e nt_Be h avior_ Framework_current.pd . Accessed December 19, 2015. Weiss A, Dantzler S. 2015. Three Key Lessons rom the Healthcare Transparency Summit. Robert Wood Johnson Foundation. http:// www.rwj .org/ en/ culture-o -health/ 2015/ 04/ 3_key_lessons_ romt.html. Accessed December 19, 2015.

9

CHAP TER

2

Value-Based Health Care for Hospitalists Christopher Moriates, MD

INTRODUCTION The eld o hospital medicine was built on the premise that hospitalists would promote and deliver more e cient, sa er, and higherquality inpatient care. Indeed, over the past decade hospitalist care has led to shorter lengths o stay and relatively lower hospital costs. However, as national health care costs have continued to rise unabated, on track to consume approximately 20% o the United States gross domestic product by 2020, the government, payers, and the public have all ocused renewed e orts on improving health care value—commonly de ned as Value =

Quality of care (including outcomes and patient experience) Costs

Hospital costs represent the single largest segment o the nearly $3 trillion annual US health care expenditure. Thus, hospitalists are vital to any e ort to rein in health care costs. This chapter reviews concepts and strategies critical or hospitalists to understand in the emerging world o value-based health care. HOSPITAL COSTS IN THE NATIONAL SPOTLIGHT In February 2013, Time magazine published an expose on health care costs, “Bitter Pill: Why Medical Bills Are Killing Us,” which was trumpeted across popular media and helped the hospital “chargemaster” become nearly a household term. The chargemaster (also known as the charge description master or “CDM”) is the list o prices or the tens o thousands o billable items at a given hospital. Shortly ollowing the Time article, the Centers or Medicare and Medicaid Services (CMS) publicly released a database o how hospitals billed Medicare or the 100 most common inpatient procedures, revealing in stark relie the ba ing amount o variation in charges and reimbursements or the same procedures between similar hospitals. Later that same year, the New York Times published a ront-page article with the headline, “As Hospital Prices Soar, a Stitch Tops $500,” continuing to shine a bright national spotlight on the issue o hospital costs. As the “Bitter Pill” and the “$500 stitch” highlighted, charges ound on hospital bills usually appear arbitrary and grossly inf ated. Despite the pressures to increase transparency, health care costs have largely remained hidden rom the public and medical pro essionals. As a result, hospitalists are generally not aware o the costs associated with their care. In addition, most clinicians nd the concepts o “charge,” “price,” “cost,” and “reimbursement” con using (Table 2-1). In most medical centers, the majority o health care transactions occur between the organization and large payer organizations, such as insurance companies or Medicare. The price or charge re ers to the amount reported on the bill to each o these payers. The cost depends on perspective; providers, payers, and patients each evaluate costs di erently: • To providers, costs are the expense incurred to deliver health

care services to patients. • To payers, costs are the amount payable to the provider or services rendered. • To patients, costs are the amount payable out-o -pocket or health care services. The chargemaster is theoretically meant to relate to both costs and payments, but since there is tremendous inexplicable variation in prices between similar organizations and because the prices are highly inf ated, the chargemaster routinely ails at this unction. Instead, the 10

C H A P T E R 2 V a l u e B a s e d H e a l t h C a r e o r H o s p i t

chargemaster is generally used as a starting point or closed-door bargaining with di erent payers. While insurance companies pay a relatively small raction o the charge on the chargemaster, uninsured patients have o ten been stuck with ull chargemaster prices. The A ordable Care Act (ACA) now ormally requires all providers to publish their chargemasters, and some states are requiring hospitals to also disclose the “allowed amount” (contractually agreed amount paid by a private insurance company) to any patient who asks. In Cali ornia, health care providers cannot bill uninsured patients an amount greater than the reimbursement the hospital would receive rom a government payer. Newer methods or determining more accurate measurements o actual costs are now increasingly being applied in health care. For example, Michael Porter and Robert Kaplan rom Harvard Business School have advocated or the use o time-driven activity-based costing (TDABC). With TDABC, the costs o space, nonconsumable equipment, and administrative overhead are all assigned minuteto-minute cost rates that are relevant to speci c processes o care. The care that is delivered over an entire episode o care is broken down into discrete activities or process steps, such as check-in, vitals and intake, physician evaluation, nursing care, and so on. A cost is assigned to each step by tracking who is doing the activity, what resources they use, which space they are in, and how long it takes them. Each item (personnel, resources, and space) is assigned a per-minute cost rate by bundling together all costs ( xed and variable) and then dividing by the total amount available or patient care. For a more detailed explanation o TDABC, one can re er to “How to Solve the Cost Crisis in Health Care” by Kaplan and Porter in the Harvard Business Review (2011). Using TDABC, some progressive medical centers have begun to establish a true “cost-master” to replace the controversial charge-master.

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Source: Moriates C, Arora V, Shah N. Understanding Value-Based Healthcare. New York: McGraw-Hill; 2015.

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Definition Account o the true cost o providing health services, de ined rom a speci ic stakeholder perspective (provider, patient, payer, society) Amount asked by a provider or delivering a service (typically more than reimbursement, used as a starting point or negotiation) Amount paid to the provider or delivering a service Amount paid by the patient or receiving a service

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TABLE 2-1 Costs, Charges, Reimbursements, and Prices in Health Care

without prices, it is easy to unwittingly order the let mignon every time. So, why not just put the prices back on the menu? Initial studies on this strategy showed mixed results, and the conventional wisdom evolved that displaying price in ormation had limited e ect, with prices o ten becoming “white noise” and being quickly disregarded. More recent studies, however, including a controlled trial at Johns Hopkins suggest that, perhaps due to the recent global attention to the importance o health care costs, clinicians are now more likely to react to price in ormation. Displaying the Medicare Allowable Rates o lab tests to hospital physicians led to substantial decreases in certain higher-cost lab tests and resulted in a more than $400,000 net cost reduction over the course o a 6-month intervention period. It is not clear i this e ect too will abate over time. Similarly, a study using dollar signs ($-$$$$) to translate relative costs o antibiotics on culture and susceptibility testing reports resulted in a signi cant decrease in prescriptions or high-cost antibiotics. Taken as a whole, a 2015 systematic review on the topic o providing price in ormation or diagnostic testing concluded that “charge in ormation changed ordering and prescribing behavior” in the majority o studies. Remaining challenges include determining which price to display (the charge, the Medicare allowable ee, the estimated marginal cost, or some other measure), as well as whether prices should be displayed or all orders or rather be limited to only speci c orders that may be ordered requently or that are associated with high cost or marginal bene t.

Recent research suggests that displaying price in ormation at the point o care may help clinicians and patients make high-value care decisions.

HOSPITAL PAYMENTS SHIFTING FROM VOLUME TO VALUE I there is one thing that most policymakers can agree on, it is that the payment system, which currently rewards volume o services delivered, should be realigned to compel the delivery o value. Not all policymakers, however, agree exactly how to best do that. Medicare’s Value-Based Purchasing (VBP) program has already tied a percentage o hospital payments to metrics o quality, patient satis action, and cost. In addition, with the proli eration o accountable care organizations (ACOs) and other bundled payment models, hospitals will continue to have an increasing share o reimbursement at risk related to the value o care that they deliver. According to the US Health and Human Services Secretary, Medicare aims to have at least 50% o all payments tied to quality or value through alternative payment models by the end o 2018.

■ MEDICARE’S HOSPITAL VALUE-BASED PRACTICE POINT

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Most hospitalists do not set the prices on the chargemaster or on hospital bills, but hospitalists can advocate or a more rational health care pricing system and or increased price and data transparency at their hospitals.

■ THE EFFECT OF PRICE TRANSPARENCY ON HOSPITALIST ORDERING PRACTICES One seemingly obvious solution to hospitalists’ lack o knowledge about costs is to provide diagnostic test prices at the point o ordering. A ter all, many have remarked that when ordering o a menu

PURCHASING PROGRAM The ederal government introduced their hospital VBP program in 2012, initially with 1% o Medicare hospital payments based on some measures o quality. This percentage will continue to rise. The rst quality indicators included process measures or pneumonia, acute myocardial in arction, congestive heart ailure, health careassociated in ections, and patient experience (largely based on patient survey responses to the Hospital Consumer Assessment o Healthcare Providers and Systems Hospital survey [HCAHPS]). Subsequently, risk-adjusted mortality, hospital-acquired conditions, and patient sa ety were added. The 2016 VBP metrics include eight clinical process o care measures, eight patient experience dimensions, three 30-day mortality outcome measures, one Agency or 11

Domain Clinical process o care

Weight 10%

Patient experience o care

25%

Outcome

40%

E iciency

25%

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TABLE 2-2 Medicare’s Hospital Value-Based Purchasing Metrics for Fiscal Year 2016 Measures Fibrinolytic therapy received within 30 min o hospital arrival in patients with acute myocardial in arction In luenza immunization Initial antibiotic selection or community acquired pneumonia in immunocompetent patient Surgery patient on a beta blocker prior to arrival that received a beta blocker during perioperative period Prophylactic antibiotic selection or surgical patients Prophylactic antibiotics discontinued within 24 h a ter surgery ends Postoperative urinary catheter removal on postoperative day 1 or 2 Surgery patient who received appropriate venous thromboembolism prophylaxis within 24 h prior to surgery to 24 h a ter surgery Communication with nurses Communication with doctors Responsiveness o hospital sta Pain management Communication about medicines Cleanliness and quietness o hospital environment Discharge in ormation Overall rating o hospital Acute myocardial in arction 30-d mortality rate Heart ailure 30-d mortality rate Pneumonia 30-d mortality rate Complication/patient sa ety indicators (AHRQ PSI-90 composite score) Catheter-associated urinary tract in ection Central line-associated bloodstream in ection Surgical site in ections in colon surgery and abdominal hysterectomy Medicare spending per bene iciary

Source: Data rom www.medicare.gov. Accessed May 8, 2015. AHRQ: Agency or Healthcare Research and Quality. AHRQ PSI-90 is a composite score consisting o eight weighted component patient sa ety indicator measures: pressure ulcers, iatrogenic pneumothorax, central venous catheter-related bloodstream in ections, postoperative hip racture, postoperative pulmonary embolism or deep vein thrombosis, postoperative sepsis, postoperative wound dehiscence, and accidental puncture or laceration.

Healthcare Research and Quality composite score, our health careassociated in ection rates, and one e ciency measure based on Medicare spending per bene ciary (Table 2-2). Payment or achieving higher-quality metrics seems to be a step in the right direction or our health care system, but there are criticisms that the current mechanism will un airly punish sa ety net hospitals and clinicians caring or the most vulnerable populations.

■ HOSPITAL COMPARE CMS hopes to also drive value through better public transparency o quality and cost data via their Hospital Compare website (www. medicare.gov/hospitalcompare). Hospital Compare provides data on a large number o metrics and even allows the public to select up to three hospitals at a time to compare head to head. In an e ort to make the website more user- riendly or public consumers, CMS recently borrowed a strategy rom the vast majority o popular rating websites and added a “star rating.” The star rating, rom one to ve stars, is initially based on validated patient experience metrics.

■ BUNDLED PAYMENTS AND ACCOUNTABLE CARE ORGANIZATIONS Whereas the VBP program is based on annual rewards and penalties, other payment models including bundled payments aim to more 12

directly incentivize quality and e ciency. Strategies or payments exist on a spectrum rom straight ee- or-service to xed global budgets. I we consider reimbursements to a hospital, a payer may pay a speci c amount or every service delivered ( ee- or-service), or each day in the hospital (Per Diem), or each episode o hospitalization (eg, Diagnosis Related Groups [DRGs]), or or each patient in their community considered to be under their care (Capitation). Alternatively, the hospital could be given a xed ee or all services per ormed on every patient during a ull year (Global Budget). Currently, the majority o payments are still primarily based on eeor-service, but this is projected to rapidly change (Figure 2-1). Bundled payments could theoretically encourage improved e ciency and reductions in hospital-acquired complications as these would lead to increased costs, length o stay, and spent resources. For example, a hospital could be paid one ee or pneumonia, regardless o the number and type o interventions or resources used. CMS has used a prospective f at ee per inpatient episode o care, based on a diagnosis-related group (DRG) system, since 1983. CMS sets the base payment amounts “ or the operating and capital costs that e cient acilities would be expected to incur in urnishing covered inpatient services.” This rate is then weighted by DRG (which accounts or relative severity o a given condition), and then adjusted according to an algorithm that accounts or a number o actors such as the regional cost o labor, and whether the hospital

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Ho s pital pro je c tio ns fo r 2019 H

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Fe e -for-s e rvic e, 34%

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Epis ode of ca re / bun dle d, 16%

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HEALTH CARE WASTE The Institute o Medicine (IOM) estimated that over $750 billion annually spent on health care does not make anyone healthier, and thus is considered waste. This represents up to more than 30 cents on every health care dollar spent. Although there are many contributors to health care waste including prices that are excessively high, unwarranted administrative costs, raud, and ine ciencies due to system errors and ailures o coordination, the largest component is unnecessary services, which includes overuse, discretionary

r e o p i t a l i s t

use beyond benchmarks, and unnecessary choice o higher-cost services (Table 2-3). Unnecessary services account or $210 billion o waste annually. This is the area o waste that individual hospitalists have the most direct control over.

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is a teaching acility. Medicare also provides higher payments or patients with “complicating or comorbid conditions,” or with “major complicating or comorbid conditions.” For particularly complex patients, Medicare provides “outlier payments” that are calculated based on an imprecise ratio o costs to charges. Global or bundle payments could potentially combine payments across di erent providers and settings, encouraging better coordination and communication between hospitals, postacute care acilities (eg, a skilled nursing acility [SNF]), and outpatient providers. This is some o the logic behind the emergence o ACOs, which were included as part o the ACA to provide an experiment in global payments and shared risk. According to the CMS de nition, ACOs are “groups o doctors, hospitals, and other health care providers, who come together voluntarily to give coordinated high quality care to their Medicare patients.” When an ACO delivers high quality care at low costs, the organization shares in the savings that the ACO achieves. Interpretations o the early results o ACOs have been mixed. The pilot Pioneer ACO program, which included 32 medical care organizations, was estimated to save 1.2% o health care spending, translating to about $400 million, over the rst 2 years. Critics point out that the pilot programs were highly selected and unlikely to represent the abilities o the rest o the health care system once the model is more widely deployed. Moreover, 13 o the 32 pilot programs had dropped out due to not achieving savings in the rst year or because they elt that the program was too complex with too many quality metrics to track. While we await additional research evidence on the true potential impact o ACOs, their premise in improving e ciency and coordinated care is strong, and their numbers will likely expand in the near uture.

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Figure 2 1 Hospital or hospital system reimbursements. (The State o Value-Based Reimbursement and the Transition rom Volume to Value in 2014. McKesson Health Solutions, 2014.)

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■ OVERUSE IS A PATIENT SAFETY PROBLEM The 1998 IOM National Roundtable on Healthcare Quality classi ed three types o health care quality problems: underuse, overuse, and misuse. However, the ollowing decade o the patient sa ety movement ocused nearly exclusively on preventable complications related to misuse. Only recently has overuse o medical care—which re ers to providing care in circumstances where the potential or harm exceeds the potential bene ts—gained attention as an important patient sa ety hazard. Overuse o medical care is a widespread problem in the US health care system. According to a 2011 study, nearly hal o primary care physicians in the United States believe that their patients are receiving too much care. Overuse o medical care can directly lead to patient harm as a result o the known risks or adverse e ects o the provided test, procedure, or medication. There are numerous requently cited instances o overuse, including inappropriate imaging, laboratory tests, antibiotics, and catheter usage (Table 2-4). For example, despite evidence and clear guidelines that suggest imaging is unhelp ul or patients with acute low back pain who lack speci c clinical ndings, routine diagnostic imaging is requently obtained or these patients. This places patients at risk or excessive radiation, costs, and substantial downstream e ects, including ine ective spine operations and perceptions o lessened overall health status. Antibiotic prescribing is another area ri e with overuse, which has led to the emergence o a number o antibiotic-resistant pathogens, making in ections more di cult to treat. When prescribed incorrectly, antibiotics pose serious risks to both individual patients and the public health at large. Antibiotic overuse can place patients at risk or allergic reactions, antibiotic-associated diarrhea, and other dangerous adverse e ects. More medical care may also lead to overdiagnosis and overtreatment, which may result in a cascade e ect o potential harms, including adverse events, mistakes, anxiety and disability, and additional unnecessary treatments. With patients bearing more 13

Areas of Waste in Healthcare Unnecessary services

Annual Amount $210 billion

Ine iciently delivered services

$130 billion

Lack o interoperability between electronic health records resulting in missing in ormation

Prices that are too high

$105 billion

Excess administrative costs

$190 billion

Fraud

$75 billion

Missed prevention opportunities

$55 billion

MRIs cost approximately $1080 in the United States and $280 in France, mostly due to di erences in price setting American medical providers spend our times as much interacting with insurance companies compared to Canadians (who have a single payer system) Billing or services that were not rendered, or “upcoding” or a procedure or diagnosis that is more complex than the actual procedure or diagnosis Failing to provide appropriate immunizations or counseling

TOTAL

$750 billion

Examples Antibiotics or nonbacterial in ections or MRIs or routine low back pain

Potential Strategies for Addressing Clinician decision making, “Choosing Wisely,” appropriateness criteria, highvalue care committees or programs Lean, care pathway redesign, accountable care organizations, electronic health record coordination Cost transparency, regulatory measures Payment re orm, insurance orm standardizations FBI and other law en orcement

Improved access to primary care, decision support systems, accountable care organizations

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TABLE 2-3 Areas of Health Care Waste

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and more o the cost o care themselves, some have urther argued that clinicians should also consider the potential nancial harm to individual patients due to excessive medical evaluations and subsequent overtreatments. The many drivers o overuse include medical culture, ee- or-service payments, patient expectations, and ear o malpractice litigation.

TABLE 2-4 Common Examples of Overuse in Medical Care Some Common Areas of Overuse Antibiotics or nonbacterial illnesses

Examples • 70% o patients with acute bronchitis are prescribed antibiotics, a rate that has been increasing over time • Antibiotic prescribing could potentially

Diagnostic imaging

be improved in 37% o common inpatient prescription scenarios, according to the Centers or Disease Control and Prevention • An estimated 3.8 million Americans receive routine imaging or low back pain each year • One-third o imaging per ormed in the

Laboratory testing

emergency department or suspected pulmonary embolism may be avoidable • Approximately 20% o lab testing may represent overutilization • Daily blood tests are routinely drawn in

Urinary and central venous catheters

many patients in the hospital, which can contribute to hospital-acquired anemia • Between 21% and 63% o urinary catheters are placed in patients who do not have an appropriate indication • According to one study, hospitalists

elt 10%-25% o peripherally inserted central catheters (PICCs) placed at their acility were inappropriate or avoidable 14

A survey study using clinical vignettes o common hospital clinical situations revealed a large amount o overuse o testing among practicing hospitalists, with 52% to 65% o respondents requesting unnecessary testing in a preoperative evaluation scenario, and 82% to 85% in a syncope work-up scenario. The majority o physicians reported that they knew the testing was not clinically indicated based on evidence or guidelines, but were ordering the test due to a desire to reassure the patients or themselves. This nding suggests e orts to decrease overuse will need to engage clinicians and patients in ways that help overcome the attitude that more testing is required to provide reassurance. STRATEGIES FOR HOSPITALISTS TO PROVIDE HIGH-VALUE CARE As payment systems and health care organizations shi t toward rewarding and supporting a ocus on value, individual hospitalists can help deliver higher value care or their patients through: (1) providing appropriate care, (2) ensuring care coordination, (3) considering patient a ordability in customizing treatment plans, and (4) leading local value improvement initiatives.

■ PROVIDING APPROPRIATE CARE Hospitalists should address the problem o overuse by directly practicing appropriate care or their patients. Emerging resources or identi ying speci c targets o common overuse include the Choosing Wisely lists, guidelines, and appropriateness criteria. The Choosing Wisely campaign (www.choosingwisely.org) is an e ort organized by the ABIM Foundation to engage specialty societies in identi ying lists o commonly overused medical services “that physicians and patients should question.” In 2013, the Society o Hospital Medicine published an initial Choosing Wisely list or both adult and pediatric hospital medicine (Table 2-5), and many other pro essional organizations’ Choosing Wisely lists (eg, American College o Physicians, American Academy o Neurology, etc) have components that apply directly or indirectly to hospital medicine practice. One strategy or encouraging and communicating appropriate care is to create a cognitive orcing unction by explicitly documenting these types o decisions in daily progress notes. For example,

Source: Adapted rom the Society o Hospital Medicine’s adult and pediatric hospital medicine Choosing Wisely recommendations. www.choosingwisely .org. Accessed May 8, 2015.

hospitalists Drs Scott Flanders and Sanjay Saint recommend including the indication, day o administration, and expected duration o therapy or all antimicrobial therapies in all progress notes and sign-outs, as an approach or curbing inpatient antibiotic overuse. Likewise, hospitalists may eliminate use o routine labs, telemetry, continuous pulse oximetry, or other recurrent interventions or monitoring by documenting daily the patient needs and reasons or continued use or ordering.

PRACTICE POINT

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Avoiding overuse is the simplest way to simultaneously enhance patient sa ety and decrease costs. Common areas o potential overuse in hospitalized patients include antibiotics, telemetry and monitoring, imaging, and routine labs.

■ THE IMPORTANCE OF CARE COORDINATION The typical hospital patient is handed o rom one physician to another more than 15 times during a single 5-day hospital stay, a rate that has been increasing with new duty hour restrictions and hospitalist sta ng models. Not surprisingly, studies show the majority o hospital patients are unable to identi y the clinician in

C H A P T E R 2 V a l u e B a s e d H e a l t h C a r e o r H o s p i t a l

More Americans than ever be ore are on high-deductible insurance plans, making them responsible or an increasing share o health care costs. As “ nancial harms” or individual patients become increasingly recognized, and more patients orgo recommended medical treatments due to out-o -pocket costs, hospitalists must customize care plans to help patients a ord their care. Hospitalists may be able to improve their prescribing practices, particularly at the time o discharge. Nearly one-quarter o hospitalized adults in a survey reported cost-related underuse in the year prior to admission, and only 16% o patients knew how much their prescribed medications at discharge would cost them. Virtually nobody had spoken to their inpatient providers about the cost o the newly prescribed drugs. Discussing drug costs with patients has been shown to be strongly associated with providing individualized lower-cost medication options. Health care pro essionals and patients can rely on an increasing number o reely available resources that provide price in ormation and cheaper alternatives or most medications (Tab le 2-6). High-value prescribing has been de ned as “providing the simplest medication regimen that minimizes physical and nancial risk to the patient while achieving the best outcome.”

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■ CONSIDERING PATIENT AFFORDABILITY

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Adult Hospital Medicine Recommendations 1. Do not place, or leave in place, urinary catheters or incontinence or convenience, or monitoring o output or noncritically ill patients (acceptable indications: critical illness, obstruction, hospice, perioperatively or 160 systolic blood pressure or > 100 diastolic blood pressure) • History o stroke • Moderate/severe peripheral vascular disease • Mild-moderate chronic obstructive pulmonary disease (COPD) (SOB, wheezing, oxygen desaturation) • Mild-moderate/stable asthma (SOB, wheezing, oxygen desaturation) • Current antibiotic treatment or pneumonia/acute bronchitis • History o upper/lower GI bleed in the last 3 mo (drop in Hgb/Hct, concern or active bleeding) • Patients on chronic enteral tube eedings or hyperalimentation/total parenteral nutrition (TPN) (in addition to nutrition team/TPN consult) • Diabetes mellitus type 1 or 2 • Stable psychiatric illnesses including a ective disorders, dementias, bipolar disorder, schizophrenia (with additional psychiatry consultation or medication concerns or decompensation o psychiatric illness) • Chronic anticoagulation (comanagement consultation on all patients) • Recent anticoagulation or deep vein thrombosis (DVT) or pulmonary embolism (PE) within the last 6 mo (comanagement consultation on all patients and possibly vascular medicine consultation) • Chronic immunosuppression (prednisone, cyclosporine, methotrexate, FK506, azathioprine, TNF-alpha blockers, etc) • Physiologic glucocorticoid treatment within the last year (≥ 7.5 mg/d o prednisone, or the equivalent, or ≥ 2 wks) • Medical issues that require medical evaluation, monitoring, or treatment:

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Atypical chest pain without evidence o an acute coronary syndrome Shortness o breath Acute DVT or PE Baseline anemia or postoperative anemia Urinary tract in ection with indwelling Foley catheter Acute delirium Electrolyte disorders Hyperglycemia without evidence o diabetic ketoacidosis (DKA) or nonketotic/hyperosmolar state Acute renal ailure Others

A portion o the payment made by CMS to hospitals is withheld i a patient experiences deep venous thrombosis or pulmonary embolism ollowing one o these procedures. While this decision has been criticized because prophylaxis is neither per ect nor risk ree, it is a reality o practice, and the hospitalist comanager must be aware o this and engage the orthopedist regarding appropriate evidencebased prophylaxis methods.

One must keep in mind that not all metrics can be expected to improve in a “positive” way; in the study described previously about hip ractures, the rates o delirium were increased, which traditionally would be perceived as a negative result. However, this was due to increased recognition, documentation, and treatment o delirium by physicians, which many would agree is a bene cial intervention. Also, these individual metrics are not in a vacuum; an increase in

TABLE 4-3 CCF Program Timeline December 2007

December 2007–March 2008 March 2008 March 2008 April 2008–July 2008 August 2008 Ongoing

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Presentation o the concept o the “embedded consultant” with a mini white paper summarizing the literature regarding bene its o comanagement by the department o orthopedics to the chairs o the Medicine Institute and department o Hospital Medicine Dra t proposal resulting rom outreach to existing programs and internal multidisciplinary planning Acceptance o pilot program by departments o Hospital Medicine and orthopedics Presentation o proposed pilot to hospital operations committee and approval o the hiring o two additional ull-time equivalent (FTE) or the program Recruitment and inalization o pilot protocols with NPs Kicko Oversight with orthopedic champion Metrics collection Creation o a link with IMPACT (preoperative clinic)

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De te rmine numbe r a nd de gre e of me dica l comorbiditie s (Ta ble 4-2)

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Pa tie nt informa tion e nte re d in s ha re d EMR lis t, IMPACT provide r notifie s coma na ge r

Cons ide r a dmis s ion or tra ns fe r to a ge ne ra l or s ubs pe cia lty me dica l s e rvice with orthope dic cons ulta tion for eve ntua l s urgica l inte rve ntion a s indica te d

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No involve me nt unle s s eva lua tion for pe riope ra tive ris k a s s e s s me nt is re que s te d

Coma na ge r s e e s a nd eva lua te s pa tie nt, ma ke s re comme nda tions a nd pla ce s a ppropria te orde rs, follows pa tie nt da ily

Gro up 4: Ac ute o r de c o mpe ns ate d c hro nic me dic al c o nditio n(s )

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Gro up 1: Patie nt has no s ig nific ant ac ute o r c hro nic me dic al is s ue s are ins ig nific ant and/o r s table

Gro up 2: Patie nt has multiple c o mplic ate d c hro nic me dic al c o nditio n(s ) o r an ac ute is s ue that re quire s me dic ine c o ns ultatio n (Table 4-2)

Gro up 3: IMPACT g e ne rate d c o ns ults (Table 4-2): Ho s pitalis t in IMPACT ide ntifie s s ig nific ant c o mo rbiditie s and re c o mme nds po s to pe rative fo llow-up by the c o manag e r

Coma na ge r s e e s a nd eva lua te s pa tie nt, ma ke s re comme nda tions a nd pla ce s a ppropria te orde rs, follows pa tie nt da ily Figure 4 1 Cleveland Clinic orthopedic comanagement triage algorithm.

TABLE 4-4 Proposed Program Metrics Volume data Case mix Patient satis action Length o stay OR cancellation rates Hospital cost and ancillary utilization Productivity measures (RVUs and billing) Provider satis action (hospitalist, orthopedist, nursing, residents) Mortality Unplanned ICU or medical service trans ers Readmission rates Quality/patient sa ety metrics JCAHO core measures

length o hospital stay coupled with decreased readmission rates might ref ect the hospitalist taking an extra hal to ull day to optimize certain medical conditions, which results in ewer readmissions or decompensation. Early results revealed that our program provided a net cost savings to the orthopedic department in terms o reduced surgical cancellations and improved patient satis action with care delivery. CONCLUSION Comanagement o specialty patients provides a novel diversity o practice to hospitalists and may be pro essional rewarding with improved collegiality with surgical specialties, opportunities or leadership, and quality improvement research. Engaging in a new comanagement relationship requires orethought and planning, and clari ying expectations, responsibilities, and metrics o success. However, when designed and managed well, a comanagement service can bene t hospitalists, surgeons, and, most importantly, the patients who trust us with their care. 27

SUGGESTED READINGS

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Fisher AA, Davis MW, Rubenach SE, et al. Outcomes or older patients with hip ractures: the impact o orthopedic and geriatric medicine cocare. J Orthopaed Trauma. 2006;20(3):172-178; discussion 9-80.

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Ja er A, Michota F. Why perioperative medicine matters more than ever. Clev Clin J Med. 2006:73(Suppl 1);2006:S1.

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Marcantonio ER, Flacker JM, Wright RJ, et al. Reducing delirium a ter hip racture: a randomized trial. J Am Geriatr Soc. 2001; 49(5):516-522.

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Sharma G, Kuo Y, Freeman J, et al. Comanagement o hospitalized surgical patients by medicine physicians in the United States. Arch Intern Med. 2010;170(4):363-368.

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Strei MB, Haut ER. The CMS ruling on venous thromboembolism a ter total knee or hip arthroplasty: weighing risks and bene ts. JAMA. 2009;301(10):1063-1065.

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Zuckerman JD, Sakales SR, Fabian DR, et al. Hip ractures in geriatric patients. Results o an interdisciplinary hospital care program. Clin Orthopaed Relat Res. 1992;274:213-225.

ONLINE RESOURCES American Academy o Orthopedic Surgeons. The Burden of Musculoskeletal Diseases in the United States: Prevalence, Societal and Economic Cost; 2012. http://www.boneandjointburden.org/. Accessed September 13, 2015. Hospital Acquired Conditions (Present on Admission Indicator). http://www.cms.gov/HospitalAcqCond. Accessed September 13, 2015. Society o Hospital Medicine. Measuring Hospitalist Performance: Metrics, Reports and Dashboards; 2006. http://www.hospitalmedicine.org/AM/Template.c m?Section=White_Papers&Template=/ CM/HTMLDisplay.c m&ContentID=14632. Accessed March 10, 2010.

CHAP TER

5

Professionalism in Hospital Medicine Kimberly D. Manning, MD, FACP, FAAP

PROFESSIONALISM Pro essionalism in medicine has long ocused on the tenets o patient wel are, patient autonomy and social justice. As health care has evolved, our de nitions and value statements have broadened. Evidence-based medicine, quality improvement, access to care, cost-e ective practices, and conf icts o interest are now at the ore ront o these discussions—all o which are salient in hospital medicine. The 2002 jointly published Medical Pro essionalism in the New Millennium: A Physician Charter articulated undamental principles and responsibilities to which all physicians should aim to maintain. The ABIM Foundation, The European Federation o Internal Medicine, and the ACP Foundation worked together to develop a charter that reconciled the self ess expectations o the physician with the ever-changing landscape o health care delivery. The American Academy o Pediatrics’ Committee on Bioethics ollowed with their policy statement on pro essionalism in pediatrics, which addressed some o the unique considerations or those caring or children. Hospitalists are trusted with the well being o some o the most vulnerable patients. This distinctive contract with society calls or some variation in our emphasis when discussing pro essionalism. Here we will de ne pro essionalism in hospital medicine, clari y concepts most applicable to those caring or hospitalized patients, and translate this into clinical practice. These concepts apply to all clinicians at all levels, team members, and hospital systems caring or patients admitted to the hospital. WHAT DOES “PROFESSIONALISM” MEAN IN HOSPITAL MEDICINE? Members o any pro ession are expected to have acquired a body o knowledge and skills speci c to their chosen eld. Through a shared commitment, there is sel -regulation and a contract with society to judiciously apply skills and expertise. Hospitalists, like all physicians, have made an agreement to heal. This pact requires an establishment o trust and a willingness to place patient needs above all other considerations. Sel -regulation is administered through state medical boards, clinical leadership, and ethical codes. Pro essionalism is what binds this treaty to our pro ession. The high stakes and lack o predictability in caring or inpatients creates unique challenges or hospitalists. Beyond the standard de nitions o medical pro essionalism, special emphasis on patient sa ety, provider interdependency and communication, nancial reimbursement and patient satis action reshape our understanding and must always be considered. Finally, with a substantial component o undergraduate, graduate and interpro essional training taking place in the hospital setting, the impact o hidden curricula in medical education is arguably greatest in hospital medicine. Given this, the ripple e ects o our behaviors are ar reaching. Pro essionalism or the hospitalist translates to more than outcomes or patients—it has the potential to de ne generational culture in medicine. PROFESSIONALISM AND PATIENT SAFETY Sa ety or hospitalized patient relies upon a collaborative work climate, teamwork, and e ective communication. Intimidating and disruptive behaviors have been linked to increases in medical errors, poor patient satis action, cost o care and higher rates o attrition or sta . Behaviors that threaten the per ormance o the health care team create signi cant barriers to quality. 29

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In 2008, the Joint Commission released a sentinel event alert addressing behaviors that undermine a culture o sa ety. From this came new requirements:

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1. Every hospital or patient care organization should have a code o conduct de ning acceptable and disruptive behaviors. 2. Hospital leadership must have processes in place or managing inappropriate or disruptive behaviors.

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Disruptive behaviors have been described as a spectrum o actions such as egregious verbal and physical actions to subtle re usals to cooperate within a system. Speci cally, this could maniest as reluctance to answer phone calls or pages, condescending intonation with nurses, colleagues and patients and impatience with queries. These behaviors are not rare in health care organizations. In a survey conducted by the Institution o Sa e Medication Practices on intimidation, as many as 40% o clinicians reported keeping quiet or remaining passive rather than con ront an intimidating person. Other surveys have revealed that such behaviors are not limited to one gender or a speci c discipline. In hospital medicine, which relies upon requent transitions o care and heavy collaboration with nurses and colleagues, this can pose signi cant threats to patients. The standard in hospital organizations should also include (but are not limited to) these additional recommendations rom the Joint Commission:

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1. Education o all team members de ned by the organization’s code o conduct with particular emphasis on respect. 2. Accountability o all team members to model desirable behaviors regardless o hierarchal rank with equitable consequences and rein orcement. 3. “Zero tolerance” or intimidating and/or disruptive behaviors with incorporation o speci c verbiage into by-laws and employee agreements. 4. Protection o those who report witnessing or experiencing disruptive behaviors through nonretaliation clauses in policy statements. 5. Timely and thorough responses to all patients and/or amilies with emphasis on acknowledgement, empathy, and apology. 6. Development o organizational processes that solicit input rom a broad representation o team members when addressing intimidating and disruptive behaviors including encouragement o ongoing interpro essional dialogue. 7. O ering training or all leaders and managers o hospital groups to build skills in team building, conf ict resolution, and eedback on unpro essional behavior. 8. Assessment o the working climate to assess perceptions o unpro essional behaviors and risk o harm to patients. 9. Provision o anonymous and con dential surveillance and reporting systems or detecting unpro essional behavior. 10. Clear documentation o all attempts to address intimidating and disruptive behaviors with outcomes. PROFESSIONALISM ISSUES AMONG HOSPITALISTS Hospitalists strive to provide uninterrupted care to hospitalized patients. Given this, transitions o care and responsibility are dependent upon respect ul interactions between providers. Provider interdependency also plays a role in patient satis action, burnout risk, and quality. Healthy relationships and working climates are essential though challenging to maintain. In a study published in the Journal o Hospital Medicine, Reddy and colleagues looked at participation in unpro essional behaviors among internal medicine hospitalists. They ound that actors most likely to underlie such behaviors were: making un o others, learning environment, workload management and time pressure. 30

Additionally, rom this study we glean that certain job and provider characteristics increased this likelihood. Hospitalists with less clinical time were more likely to make un o other colleagues. It is postulated that those with heavier clinical loads have more opportunities to orm relationships and are thus more apt to avoid unf attering commentary o others. Moreover, more clinical time could also cause hospitalists to be less easily inf uenced by the opinions o others. Night work and age also seemed to be actors in unpro essional behaviors. Those working at night elt more pressure to wrap up work. Hasty handovers and celebration o intercepted admissions are just a ew things that could happen as a result. Given the understanding that unique characteristics increase the incidence o unpro essional behaviors, special attention should be given to more junior hospitalists as well as those with night shi ts, limited clinical duties due to competing priorities, and at sites known or heavier workloads. E orts to better understand the reasons or participating in these behaviors should continue to be explored. PROFESSIONALISM AND PATIENT SATISFACTION Patient satis action is linked to reimbursements and is a key actor in determining quality o care. Interestingly, the technical dimensions o quality o care are rarely called into question with regards to hospitalized patients. Instead, perception o quality or patients is most connected to what is personally valued by patients and their amilies. Among those things being treated with respect and dignity coupled with clear communication around treatment decisions are areas that have been identi ed to be o paramount importance to patients. Pro essional behaviors are generally the de ning eatures o these perceptions. Surveys have been developed to best ascertain patient satis action in hospitals. The Hospital Consumer Assessment o Healthcare Provider and Systems (HCAHPS) is now the core metric against which health care systems are evaluated. As the rst national, standardized and publicly reported survey o patients’ viewpoints on hospital care, HCAHPS now serves as a tool or valid comparisons between hospitals locally, regionally and nationally. A random sample o patients receives this survey between 48 hours and 6 weeks a ter discharge. Among the 32 questions about their hospitalization, patients are asked to recall their perceptions o physician and nurse communication, responsiveness o hospital sta , communication about medications and care transition. Though HCAHPS data are not limited to hospitalists, as the “ ace” o the hospitalization or many patients their impact can be substantial. Special attention to communication skills training, strategic planning around availability to patients and enhanced discharge paperwork and medication reconciliation are just a ew measures that have been shown to improve potential areas o weakness. Other simple tips have been o ered to enhance patient satis action and experience include: • Make a positive patient experience a part o the culture. • Adopt patient-centered, multidisciplinary rounds with trans• • • •

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parent discussions that include patients. Avoid giving o cues o indi erence or uncaring (eg, rushing, lack o eye contact, standing instead o sitting). Encourage every employee to think about purpose and people, not just tasks. Equip every team member with skills or handling patient or amily member complaints. Recognize that system inadequacies can be responsible or individual lapses in pro essionalism. Unreasonable scheduling algorithms and workloads are examples o system issues that can undermine pro essional behavior. Collect and act on data related to patient satis action.

The hospital setting accounts or a substantial proportion o learning environments in undergraduate and graduate medical education. Given this act, the importance o pro essionalism must be emphasized or hospitalists through institutional e orts and programs. Medical education literature in orms us that learners report that values exhibited by their teachers and institutions directly impact their own pro essionalism. Regrettably, a majority o medical students endorse witnessing peers and supervising physicians speaking o patients and/or other health care pro essionals in unf attering, cynical or derogatory ways. Multiple studies have shown that the humanistic attitudes essential to patient-centered care unravel during medical school and residency, increasing the risk o burnout and depression. Hospital medicine provides much o the backdrop or this “hidden curriculum,” originally described by Ha erty as “a set o inf uences that unction at the level o organizational structure and culture.” There can be pro ound dichotomy between the negative behaviors exhibited by some physician role models and the desired attributes described in ormal curricula. The insidious nature o a hidden curriculum is power ul enough to become institutional culture. Newer mandates through accreditation organizations call or more honest appraisals o the in ormal inf uences on learners. They also charge institutions with building ongoing strategies to reshape and mitigate their untoward e ects. NEW CONSIDERATIONS

■ PROFESSIONALISM AND DIRECT PHARMACEUTICAL MARKETING The interaction between physicians and the pharmaceutical industry and its sales representatives remains controversial. Though lessening in requency, direct marketing (usually trade name drugs) promoted to providers and groups through gi ts, sponsored meals and lectures, travel and symposia are not oreign to most physicians. Though clinicians do not typically report that such interactions inf uence their prescribing practices, evidence supports otherwise. A large meta-analysis o over 500 studies revealed that attending sponsored CME events, accepting unding or travel, and participating in pharmaceutical sponsored lectures were associated with

C H A P T E R 5 P r o e s s i o n a l i s m i n H o s p i t a l M e d i

Social media has rede ned the inter ace between physicians, patients, learners, and the public. The once passive viewing o content on early iterations o the websites has exploded over the last decade to include interactive exchanging, sharing and communication in real time. Facebook, Twitter, Instagram, and LinkedIn are among the most widely used social media plat orms, all made even more accessible by recent advances in mobile smartphone technology and their near universal use by the public. As o 2014, it was estimated that more than 1 billion people were on Facebook and, o these individuals, nearly 400 million only log in using mobile smartphones. Tablets, Internet ready televisions and even smart watches, all with capability to access these same social media platorms, have also emerged in very recent years. These developments, along with more unrestricted Wi-Fi “hotspots” (even in most hospitals) and robust search engines using collective intelligence tools, have closed the gaps that once stood between the pro essional and private personas o physicians. Though social media presents new challenges to the landscape o medical pro essionalism, it also presents opportunities. Speci c health in ormation can be quickly disseminated to large groups o individuals in moments. Plat orms aimed toward health pro essionals such as Doximity o er encrypted, HIPAA compliant privacy settings or idea sharing, consultation, and collaboration in ways previously un oreseen. Moreover, Twitter use at pro essional meetings keeps attendees and allows those unable to leave the hospital to stay abreast o ongoing activities as they are happening. In less than hal o a decade this culture o “tweeting” pro essional meetings in real time has become not only a welcomed eature but an expected one as well. A growing number o academic institutions and organizations have begun to develop policies about judicious use o social media, most o which emphasize con dentiality. Pro essional development centered on social media is becoming more requent on meeting agendas. From concrete tips on privacy settings to abstract ways to seize collaborative opportunities, hospitalists and other health care providers should all gain some pro ciency with social media and its potential impact on the care o patients.

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A medical school ensures that the learning environment o its medical education program is conducive to the ongoing development o explicit and appropriate pro essional behaviors in its medical students, aculty, and sta at all locations and is one in which all individuals are treated with respect. The medical school and its clinical a liates share the responsibility or periodic evaluation o the learning environment in order to identi y positive and negative inf uences on the maintenance o pro essional standards, develop and conduct appropriate strategies to enhance positive and mitigate negative inf uences, and identi y and promptly correct violations o pro essional standards.

■ PROFESSIONALISM AND SOCIAL MEDIA

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The Accreditation Council o Graduate Medical Education (ACGME) and the Liaison Committee on Medical Education (LCME) have identi ed pro essionalism as a crucial competency or developing physicians and have labored to build program requirements around this expectation. For example, the LCME uses this verbiage in their accreditation data collection tools or medical schools:

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certain prescribing and pro essional behavior. Institutional policies are in place at many hospitals regarding disclosure o conf icts o interest. This continues to be an important discussion at the level o policy and education, as well as among pro essional organizations such as Society o Hospital Medicine (SHM), American College o Physicians (ACP), and Society o General Internal Medicine (SGIM).

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Hospitalists are poised to have great impact in all o these areas through their continuum o contact throughout the hospitalization. Intentional approaches to both individual behaviors and the systems in which hospitalists work are essential.

CONCLUSION Hospitalists, with their large imprint in medical education and contract to care or a diverse and vulnerable patient population, must approach pro essionalism with intentionality. New considerations such as direct pharmaceutical marketing and social media have shi ted prior understandings o what it means to be a medical proessional. Thought ul consideration o pro essional behaviors along with their impact on patient sa ety, patient satis action, and the hidden curriculum should guide ongoing individual, institutional and organizational development.

SUGGESTED READINGS Gholami-Kordkheili F, Wild V, Strech D. The impact o social media on medical pro essionalism: asystematic qualitative review o challenges and opportunities. J Med Internet Res. 2013;15(8):e184. Ha erty FW. Beyond curriculum re orm: con ronting medicine’s hidden curriculum. Acad Med. 1998;73(4):403-407. 31

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Joint Commission: Behaviors that undermine a culture o sa ety. Sentinel Event Alert. vol. 40. http://www.jointcommission.org/ sentinel_event_alert_issue_40_behaviors_that_undermine_a_ culture_o _sa ety/. Accessed July 9, 2008.

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Project o the ABIM Foundation, ACP–ASIM Foundation, and European Federation o Internal Medicine. Medical pro essionalism

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in the new millennium: a physician charter. Ann Intern Med. 2002;136:243-246. Rosenstein AH, O’Daniel M. A survey o the impact o disruptive behavior and communication de ects on patient sa ety. Joint Comm J Qual Patient Sa . 2008;34(8):464-471. Swick HM. Toward a normative de nition o medical pro essionalism. Acad Med. 2000;75(6):612-616.

CHAP TER

6

Principles o Leadership Steven Weinberger, MD, FACP

Physicians are requently called upon to take on leadership roles. These roles can come in various orms, ranging rom academic leadership roles (eg, division or department chie or chair) to educational leadership roles (eg, clerkship or residency program director) to leadership roles in a practice setting (eg, director o a practice group). Although some o the desired skills and competencies or the leader may be speci c to particular roles and responsibilities, others are more generic and applicable to any o these leadership positions. This chapter concentrates initially on the generic aspects o leadership and concludes by discussing some o the challenges that are more speci c to hospitalists and to the hospital environment. In addition, instead o trying to review the voluminous leadership literature, presented here will be a personal perspective, based upon experiences in a variety o leadership positions over many years. Discussion o leadership will be divided into our primary components: the personal attributes that a leader should demonstrate, the skills that should be acquired, a suggested approach to reach a goal, and leadership challenges or hospitalists in the hospital environment. LEADERS VERSUS MANAGERS Be ore considering the important attributes o a leader, it is worthwhile to understand the distinction between a leader and a manager. Much has been written about these di erences, which can be readily summarized and understood by any o several descriptions or aphorisms: • Leaders have ollowers; managers have subordinates. Individu-

als voluntarily ollow a leader because o the qualities o the leader; subordinates work or managers because o the reporting relationship and the organizational authority vested in the manager. • Leaders lead people; managers manage tasks. • Leadership is doing the right thing; management is doing things right. • Managers ocus on tactics and tasks; leaders ocus on strategy and direction. In act, however, these distinctions o ten blur in the setting o actual roles and responsibilities in the workplace. The individuals who are most success ul in assuming roles with greater authority and responsibility are those who are both e ective leaders and e ective managers. A leader who does not have good management skills can generate visionary ideas but will be unable to implement or operationalize them. A manager who does not have good leadership skills will be unable to mobilize and motivate a supportive team. Some activities and responsibilities o a physician leading a group o hospitalists can readily illustrate the di erences between leadership and management. “Managing” the group means assuring that the patients are covered, that transitions o care are e ectively handled, that chart and billing documentation is complete and accurate, and that teaching responsibilities are assigned and well integrated with patient care responsibilities. In contrast, “leading” the group means exploring and developing ideas or improving the system and its productivity, improving quality o care, developing the skills o the team, and acilitating the pro essional development o the team members. For the purposes o this chapter, I will primarily use the terms “leadership” and “leadership skills,” recognizing, however, that we 33

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are really considering both leadership and management skills. In the medical leadership positions that are likely to be assumed by readers o this chapter, success will hinge upon both leadership and managerial qualities and the importance o each in rein orcing the other. There ore, the approach here to discussing leadership and management qualities will be one o lumping rather than splitting. DESIRABLE ATTRIBUTES OF THE LEADER

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A leader must demonstrate pro essional integrity, including honesty. High standards o integrity and honesty are a prerequisite or obtaining the respect o colleagues, superiors, and subordinates. The leader sets the model o behavior or the rest o the team, and lack o pro essional integrity exhibited by the leader will soon be mirrored by cracks in pro essionalism among others. The leader needs to be an e ective communicator; openness and transparency in communicating to all constituencies assure that everyone is on the same page. A commonly held perception o a talented leader is o ten someone who can communicate both values and vision, including a set o goals and how those goals might be achieved. However, that is only part o the communication equation, which also involves establishing and transmitting expectations or others. It is critical that subordinates, trainees, and team members understand the expectations being placed on them, including how and on what basis they are being judged. Communication must also occur on a two-way street, that is, the leader must be an excellent listener as well. I the leader is unable or unwilling to hear what others have to say, he or she will be doomed to ailure. Without ideas and eedback rom others, the leader will invariably make mistakes o both commission and omission that can be avoided by hearing the ideas and opinions o others and considering all perspectives when making important decisions. Another important aspect o communication relates to eedback. The e ective leader provides eedback in a constructive, pro essional manner. This eedback must be based on established expectations, not on the subordinate’s or trainee’s ability to read the leader’s mind and guess what s/he wants. In addition, the eedback should be done in a way that is ormative, that is, giving the receiver o the eedback an opportunity to, and advice on how to improve per ormance. Providing only summative eedback at the end o a responsibility or task allows no room or improvement and o ten proves rustrating to the person receiving the eedback. An e ective leader remembers that success is determined by the contributions or development o the people s/he leads or trains. The leader must acknowledge the contributions o others and not always take credit or success. Nothing is as demoralizing to a team member as the eeling that his contributions are not being recognized and that someone else is taking credit or his work or accomplishments. At the same time, a success ul leader is cognizant o , and aims to promote the pro essional development o the individuals or which she is responsible. For example, true success or an academic leader is o ten determined as much by the ultimate careers o the individuals trained by the leader, as it is by the academic contributions o the leader himsel . Supporting the pro essional development o one’s trainees is one o the most important and enduring legacies that a leader can leave to the pro ession. Finally, an intangible but critical quality o a success ul leader is the ability to create and maintain a positive work environment. The leader needs to establish a workplace tone that is positive, in which people eel they are supported and a “can do” attitude prevails. Productivity o the individuals or whom a leader is responsible is dependent upon their interest in, and commitment to the team and to the shared goals and vision that have been de ned by the leader. A setting in which individuals are competitive with each other, where back-biting is common, and people eel they do not 34

respect and share the values o their colleagues and the leader, is not an enjoyable workplace. It is also one that will never reach its true potential. LEADERSHIP SKILLS An important prerequisite or a success ul leader is a high level o competence in the particular eld related to the leadership role. For example, an educational leader must be accomplished as a teacher and educator in order to command the necessary respect o trainees and other educational colleagues. Similarly, a clinical leader must be highly regarded as an excellent clinician in order to have credibility with other clinicians. Another important skill that leaders must acquire is the ability to negotiate e ectively. This topic is covered extensively in a later chapter (Chapter 26, Negotiation and Con ict Resolution), but it is important to stress that leaders must exercise their negotiation skills in many settings—when dealing with superiors, dealing with subordinates, or dealing with third parties with whom there is no reporting relationship. Physicians typically have not been trained in negotiation, but ortunately a number o excellent and readily accessible resources can provide valuable guidance to the previously untrained leader. Many leaders have responsibility or budgets, and a working amiliarity with balance sheets and with revenue and expense statements is there ore use ul. Although providing such nancial training is beyond the scope o this chapter, a valuable resource that can provide basic training in the principles o accounting is a short, easy to read, programmed text used in many business schools. Finally, the responsibility o running meetings o ten accompanies leadership roles. Everyone has participated in meetings that run e ectively, where the participants eel they have not wasted their time, and they leave the meeting with a well-de ned action plan. On the other hand, everyone has also participated in meetings that are poorly organized, do not make best use o participants’time, and do not have a well-de ned purpose or outcome. Several important aspects o well-designed meetings include: • Sending an advance agenda to the participants, so that

they can prepare appropriately. • Starting on time and f nishing on time (or early). Time is an incredibly valuable commodity, and meeting participants become distracted and resent ul when time is wasted at the beginning o a meeting or when a meeting runs overtime and potentially a ects their subsequent commitments. • Assuring that the meeting is interactive and makes good use o the participants’ time and expertise. A success ul meeting is not a monologue provided by the meeting coordinator. Rather, it involves active engagement and participation by all attendees, so that the participants eel they have contributed to the meeting and have not just been wasting their time. • Wrapping up the meeting with a summary and a welldef ned action plan. Everyone should understand the outcome o the meeting and the expected action plan, including the assignments that have been meted out to individuals and the timeline according to which they should be completed. REACHING A GOAL In trying to generate ideas and complete desired tasks necessary to reach a goal, the success ul leader may nd it help ul to use a set o principles: (1) establish the goal, (2) identi y and include stakeholders, (3) assemble a team, (4) engage all team members to generate ideas, (5) accept ideas rom outside the team or organization, (6) delegate responsibility, and (7) assess interim outcomes and reassess the plan.

LEADERSHIP CHALLENGES IN THE HOSPITAL ENVIRONMENT Hospitalists who are in leadership positions or who are expected to e ect change are o ten con ronted with challenges that arise speci cally rom working in the hospital environment. Besides dealing with

C H A P T E R 6 P r i n c i p l e s o L e a d e r s h i

physicians, hospitalists are constantly working with nonphysician personnel and administrators whose management and reporting structure is quite independent o the physicians at the institution. A hospitalist leader who is trying to e ect change but is not part o the hospital’s administrative hierarchy may have dif culty shaping opinions and getting buy-in rom a group o nursing leaders or rom nonphysician hospital administrators. Even among physician leaders at the hospital, challenges arise o ten centered around a competition or resources, so that the interpersonal relationships become adversarial rather than cooperative. An additional challenge con ronted by hospitalists stems rom their basic demographic characteristics. Age, gender and even race could impact abilities to break into a hospital hierarchy that tends to be older, male, and Caucasian. A young physician who goes on sta as a hospitalist at the institution where s/he completed residency may nd it dif cult to shake the image o being a resident rather than a sta member and colleague. On the other hand, a young hospitalist who takes a position at an institution where s/he did not train may nd it dif cult to parachute in as a newcomer un amiliar with a particular hospital’s culture and personalities. Although there are no proven methods to overcome such challenges, some strategies may be help ul. First, it is extremely valuable to obtain the trust and support o a more senior, well-respected person, ideally a current physician leader at the institution. Such an individual not only can serve as a mentor and advisor to guide the hospitalist in charting a path through un amiliar territory, but s/he can also smooth the way or the young hospitalist to become accepted by the more established hospital hierarchy. For example, the support and trust rom a well-respected division chie or department chair can be invaluable in easing the way or a hospitalist to deal with an older, potentially intimidating chie o surgery or hospital’s chie operating of cer. Second, as mentioned earlier in this chapter, it is critical or any clinician leader, particularly a hospitalist leader, to be viewed by both physician and nonphysician sta as an outstanding clinician. It is very dif cult to have credibility in the hospital environment, particularly rom physician colleagues and rom nursing sta , i one is viewed as a “clinical lightweight.” The hospitalist’s conscientiousness, clinical skills, decision-making ability, communications skills, and pro essionalism all contribute to the individual’s reputation and ability to command respect rom others at the institution. Third, when trying to e ect change and garner support rom both physician and nonphysician sta , the hospitalist leaders must initially establish, promote, and ocus on the principles underlying any proposed plan. Although it is easy or a hospital administrator to argue with a speci c proposal, it is much more dif cult to take a position against an ultimate goal o improving the quality and sa ety o patient care, improving hospital systems and ef ciency, or improving the nancial per ormance o the hospital. Finally, it is important or the hospitalist to seek out de ned leadership roles. Such roles can obviously be within the hospital community, or example, by serving on committees. However, establishing a presence and reputation outside the institution, or example, through involvement at regional and national levels, can only help the hospitalist’s reputation and credibility within her own hospital setting.

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At the outset, the leader needs to establish the goal and communicate it to others. In other words, the leader must de ne the destination be ore anyone can plot the route o how to get there. Success in achieving a goal depends critically upon the process o engaging others at least as much as the goal itsel . This process involves identifying stakeholders who are either impacted by the goal, or who will eel disen ranchised i they have not been included in developing or working to achieve the goal. For example, i a residency program director needs to restructure a schedule or the residents based upon changing regulatory requirements, s/he is much more likely to be success ul when including residents in developing the new model, rather than imposing it upon them without their input. No matter how sound an idea or plan, its acceptance and implementation can be obstructed by those who were not included or engaged—but eel they should have been—in its generation and development. In making plans or a project or reaching a goal, the leader o ten needs to establish a team o individuals who can work together. Assembling the right people is critical or a success ul outcome. Team members need to be chosen based upon their skills, their interest in and enthusiasm or the project, their ability to work well with others on the team, and their openness in providing ideas and eedback about how things are going. Once the goal is established, stakeholders are identi ed, and the team is assembled, the leader must recognize that s/he does not need to generate all the ideas. Great work is typically done in teams in which everyone is encouraged to share ideas, no matter how crazy or ar- etched they may initially seem. In addition, not all good ideas need to come rom within the team. One can adopt and build upon ideas and success ul initiatives that have been developed by individuals outside the organization. The “not invented here” attitude o ten precludes an open mind to accepting ideas that have worked success ully in other settings. The ideas necessary to reach a goal are o ten not grand and sweeping ones. A series o small steps, each o which can be judged and modi ed as necessary based upon the outcome achieved, is o ten more success ul than a single, revolutionary idea that does not allow or opportunities to provide mid-course assessment and correction. In making the best use o the team members, the leader must be willing to delegate responsibility appropriately. From the time o their training, physicians are o ten used to eeling that they need to take ull responsibility or a patient, and this attitude o individual responsibility and accountability should o ten be modi ed when one assumes leadership responsibilities. Members o a team work best when they eel that responsibility has been bestowed upon them. Delegating responsibility is not a sign o weakness; rather, appropriate delegation demonstrates an understanding o how to share responsibility, engage others, make best use o available resources, and capitalize on each person’s strengths. As a project progresses, the leader must critically assess interim outcomes. Based upon these outcomes, the leader must be willing to reassess the plan and adjust accordingly. The leader and the team members should also recognize that not all plans will be success ul. A plan that does not succeed should not necessarily be viewed as a ailure. Important lessons are o ten learned and new ideas generated based upon unanticipated problems or unexpected results.

FINAL WORDS The concept o being a “born leader” has clearly given way to a philosophy that leadership skills can be learned. It is perhaps based on this premise that so many books and articles have been written about every possible aspect o leadership. Yet, it is air to say that many personal qualities and aspects o personality do have an impact on potential success as a leader. When placed in a position 35

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with leadership responsibilities, it is valuable to take some time to sel -re ect upon personality traits and how they will likely in uence leadership style. In addition, one should try to assess what additional skills s/he needs to acquire to be an e ective leader. Even though physicians are o ten placed in either clinical or academic leadership positions, they have not typically received leadership training. Recognizing the interplay between personal style and leadership skills, and acknowledging the importance o sel -re ection on successes and ailures as a leader will serve to make one an increasingly e ective leader over time.

36

REFERENCES Breitner LK, Anthony RN. Essentials of Accounting. 11th ed. Upper Saddle River, NJ, Prentice Hall, 2012. Fisher R, Ury W, Patton B. Getting to Yes: Negotiating Agreement without Giving. New York, NY: Penguin Books; 2011. Updated and revised ed. Shell GR. Bargaining for Advantage: Negotiation Strategies for Reasonable People. 2nd ed. New York, NY: Penguin Books; 2006.

SECTION 2 Critical Decision Making at the Point of Care

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CHAP TER

7

Principles o Evidence-Based Medicine and Quality o Evidence Daniel I. Steinberg, MD

INTRODUCTION

■ A BRIEF HISTORY The March 1, 1981 issue o the Canadian Medical Association Journal included a landmark article titled “How to read clinical journals: I. Why to read them and how to start reading them critically.” Written by David Sackett, MD (1934–2015) o McMaster University, it introduced a series o articles that highlighted the importance o critical appraisal o the literature. Starting in 1993, a set o articles in the Journal of the American Medical Association titled “Users’ guides to the medical literature” reprised and expanded on the earlier series. These works, and other e orts by their authors, made critical appraisal o the literature accessible to the masses and laid the groundwork or evidence-based medicine (EBM). Gordon Guyatt, MD, coined the term “evidence-based medicine” in the early 1990s, while he served as the internal medicine residency program director at McMaster University. Dr. Guyatt and colleagues had incorporated critical appraisal o the literature into the residency program curriculum, and Dr. Guyatt wanted a term to describe and advertise their e orts. EBM caught on quickly over subsequent years as practicing physicians and training programs embraced and taught its methods, with dissemination greatly ueled by the rise o the Internet.

■ ROLE OF CLINICAL JUDGMENT AND PATIENT PREFERENCES IN EBM An early criticism o EBM, which some still harbor, was that it did not properly acknowledge the importance o clinical judgment or patient pre erences. In an updated ramework or evidence-based practice by R. Brian Haynes, P.J. Devereaux, and Gordon Guyatt in 2002, evidence-based decisions are based on our cardinal elements: (1) the research evidence, (2) the patient’s clinical state and circumstances, (3) the patient’s pre erences, and (4) the clinician’s judgment and expertise.

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Clinical judgment and expertise are essential to the practice o EBM. These skills acilitate optimal decision making by allowing the clinician to properly weigh the research evidence in the context o the patient’s individual clinical circumstances and pre erences. Decisions should never be based on the evidence alone.

Practicing EBM may appear to be a straight orward a air with its methodical approaches to clinical question construction and to searching and critically appraising the literature. However, hospitalists should not con use process with content, and they will o ten nd that EBM tends to highlight clinical uncertainty and gaps in the medical literature. High-quality evidence does not exist to guide all clinical decisions, and extrapolation rom lower quality evidence is o ten necessary. Bayesian diagnostic decision making o ten relies on clinical judgment to ormulate pretest probabilities or to deal with the uncertainty that accompanies inconclusive post-test probabilities. Learning to deal with uncertainty is a core competency o EBM, which draws heavily on clinical judgment and experience. 39

STAYING UP TO DATE WITH THE LITERATURE P

■ PUSH INFORMATION RESOURCES

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Few clinicians have the time to consistently read medical journals, identi y relevant new research and critically appraise new studies to determine i they should be incorporated into one’s practice. “Push” in ormation resources are resources that send content out to their users on a regular basis. “Pull” in ormation resources are databases that clinicians search in order to answer a clinical question. Pull resources are discussed later in this chapter. Tab le 7-1 lists selected high-quality push and pull in ormation resources. McMaster PLUS (Premium Literature Service) continuously searches over 120 medical journals and selects evidence or critical appraisal. Articles that pass the critical appraisal process and are also rated as clinically relevant and newsworthy by their team o reviewers are then trans erred to the PLUS database. The PLUS database contributes content to evidence-based summary resources such as EvidenceUpdates, ACP JournalWise, DynaMed, and ClinicalEvidence. These resources all o er e-mail alerts to users. ACP Journal Club and NEJM Journal Watch critically appraise and produce synopses o high-quality evidence accompanied by expert commentary. PubMed, through its ree account service “My NCBI,” allows users to receive the results o literature search strategies they either design or select (via the “Clinical Queries” eature) by e-mail on a regular basis.

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TABLE 7-1 High-Quality Push and Pull Resources Push Resources

Pull Resources

Resources that automatically send new, high-quality evidence to users via e-mail or RSS eed aggregator

Databases that are searched as needed to answer clinical questions

ACP JournalWise http://journalwise.acponline. org

ACP Journal Club http://annals.org/journalclub. aspx

BMJ Clinical Evidence http://clinicalevidence.bmj. com

BMJ Clinical Evidence http://clinicalevidence.bmj. com

DynaMed https://www.dynamed.com

Cochrane Collaboration http://www.cochrane.org

Evidence Updates https://plus.mcmaster.ca/ evidenceupdates

DynaMed https://www.dynamed.com

NEJM Journal Watch http://www.jwatch.org

NEJM Journal Watch http://www.jwatch.org

PubMed (using an My NCBI account and search strategies created by the user, see text) http://www.ncbi.nlm.nih.gov/ pubmed

Practice Guidelines rom pro essional societies, eg, AHRQ National Guideline Clearing House http://www. guideline.gov PubMed http://www.ncbi.nlm.nih.gov/ pubmed Trip Database https://www.tripdatabase.com

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Hospitalists should strongly consider using an e-mail-based alerting service or RSS (Rich Site Summary) eed aggregator rom a high-quality evidence-based summary push resource to e ectively stay up to date on the literature. Hospitalists can pair a virtual le cabinet with these resources to orm an e ective in ormation management system that will make evidence readily available at the point o care.

■ KEEPING INFORMATION AT HAND: THE VIRTUAL FILE CABINET Although the traditional way o storing articles or later re erence is to use a physical le cabinet, this approach has a number o disadvantages. File cabinets are not mobile, they cannot be quickly searched or updated, and determining how to best le something or easy retrieval can be con using. A clinician might ask himsel / hersel in rustration: “Did I le that great article on pulmonary maniestations o HIV under ‘HIV,’ or ‘in ectious disease,’ or ‘pulmonary’?” They do not o er a way to electronically add content to them or electronically share content with others, making them incompatible with modern communication methods such as e-mail. The virtual le cabinet (VFC) is an Internet cloud-based electronic document storage system that synchronizes across multiple electronic devices (eg, smartphone, tablet, laptop computer). A VFC is an e ective way or hospitalists to electronically le articles they receive rom a push in ormation resource as described above or easy retrieval at the point o care. Box, Dropbox, Evernote, and Google Drive are some examples o the commercial products that currently exist that can be used as a virtual le cabinet. Products such as these also o er easy options or electronically sharing content with others. THE EBM PROCESS: ASKING AND ANSWERING CLINICAL QUESTIONS Practicing EBM o ten involves asking and answering questions that arise during the care o patients. There are our steps in this process: (1) asking a ocused clinical question, (2) searching the literature or the best available evidence, (3) critically appraising the literature, and (4) applying the literature to an individual patient. This chapter explores the basic principles o EBM as they relate to these our steps.

■ STEP 1: ASKING A FOCUSED CLINICAL QUESTION Clinical questions all into two general groups: background or oreground questions. Background questions ask about general knowledge, pathophysiology, epidemiology, and broad aspects o diagnosis and treatment. “What are the treatments or epilepsy?” is an example o a background question. Junior learners o ten ask background questions, and answers can o ten be ound in textbooks. Foreground questions are more ocused, address speci c clinical situations, and acilitate the delivery o the most up-to-date, evidence-based care. Experienced clinicians ask oreground questions, with answers residing more in the medical literature. Hospitalists should always aim to construct ocused oreground questions. These are urther discussed below. Most hospitalists would recognize the question, “Should patients with heart disease receive regular vaccinations?” as one that is overly broad. Not all heart diseases are the same, nor are all vaccinations, and the speci c bene ts patients might reap rom vaccination are not speci ed by the question. Clinical questions need to be ocused in order to be answerable. In addition to clinical questions about therapy, clinicians can ask ocused clinical questions about diagnostic tests, about the harm an intervention might cause, about prognosis, or about di erential diagnosis.

C H A P T E R 7 P r i n c i p l e s o E v i d e n c e B a s e d M e d i c i n e a n d Q u a l i t y o E v

With a properly constructed clinical question in hand, the hospitalist can now search the literature to nd the answer. The rst step is to select an in ormation resource that is appropriate or the clinical question and the amount o time available. Databases that are searched in an on-demand way in order to answer a clinical question are called pull resources. In many cases, and especially when time is limited, one should rst consult a high-quality summary pull resource. Summary resources that are requently updated assess the quality o the evidence presented and are user- riendly and pre erable. Examples include BMJ Clinical Evidence, ACP Journal Club, DynaMed, the Cochrane Collaboration, NEJM Journal Watch, UpToDate, and practice guidelines rom pro essional societies. All are highly use ul. Each has its strengths and weaknesses. UpToDate is ast to use, comprehensive, and provides expert guidance in an easy to digest, narrative ormat, but it is not as rigorously constructed as the others. ACP Journal Club provides excellent summaries o highly selected literature deemed valid and relevant to clinical practice, but as a result its database is not comprehensive. DynaMed is rigorously constructed and presents a lot o primary data rom clinical trials, o ten in an outline ormat. The Cochrane Collaboration produces high-quality systematic reviews o the evidence. Practice guidelines are excellent resources that o er clear recommendations, but their quality can vary, update intervals can be long, and users must pay close attention to the level o evidence and strength o recommendations in published practice guidelines. I one has more time, or i a deeper dive is needed a ter consulting a summary resource, the primary literature can be searched via PubMed (pre erably using “Clinical Queries” option or clinical questions) or Trip Database (pre erably using “PICO search” option or clinical questions). For certain questions, a content-speci c resource

Hospitalists should know which types o clinical trials will best answer di erent types o clinical questions, and which study designs will provide the most power ul results. The randomized controlled trial (RCT) is the gold standard or determining the e ect o a therapeutic intervention. Determining the accuracy o a diagnostic test requires a prospective design in which the test is studied in the same clinical setting it will be used, and is compared against an acceptable gold standard. The e ect o a diagnostic test on clinical outcomes can be determined by a randomized controlled trial, in which the test in question is treated as the intervention and another diagnostic approach (pre erably a gold standard i available) is considered the comparison. A systematic review is a summary o the evidence on a topic in which the literature search and selection o evidence has been perormed in a rigorous, transparent, and reproducible way. The most valuable systematic reviews will also include a meta-analysis. In a meta-analysis, the results o multiple similar types o studies (RCTs, observational studies, or studies o diagnostic tests) are statistically combined to o er more power ul results. What a meta-analysis gains in power, it can sometimes lose in applicability and ocus i too much clinical heterogeneity exists among the patients included rom individual studies. With that caveat, a high-quality systematic review that includes a meta-analysis is considered to be the highest level o evidence. Table 7-2 describes the hierarchy o evidence or di erent types o clinical questions.

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■ THE HIERARCHY OF EVIDENCE

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■ STEP 2: SEARCHING THE LITERATURE

Pull resources are databases that are searched in an on-demand way to answer a clinical question. Pull resources have di erent and o ten complementary roles. None are per ect, and hospitalists should adopt a “toolbox”approach in which they become amiliar with a ew resources. The type o question and the amount o time available to answer the question should help determine which resource the hospitalist consults.

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Clinical questions must be ocused to be answerable. Hospitalists should use the widely accepted “Population– Intervention–Comparison–Outcome”(P-I-C-O) ormat to construct ocused clinical questions.

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can be best. JAMAEvidence catalogs evidence on the accuracy o history and physical exam ndings. The Cochrane Collaboration ocuses on systematic reviews. No single resource is per ect and clinicians should adopt a “toolbox” approach by becoming amiliar with a ew resources.

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Clinical questions should be constructed using the “P-I-C-O” ormat. “P” stands or “population” and describes the patient the question is about in proper detail. “I” stands or “intervention” and re ers to the therapy or diagnostic test in question. “C” stands or “comparison” and describes either an alternative treatment or standard o care ( or questions about therapy) or the gold standard test ( or questions about diagnostic tests). “O” stands or “outcome,” which should be clinically important and patient-centered. Surrogate markers o clinically important outcomes are acceptable. An example o a well-built clinical question about therapy is: “In patients admitted to the hospital with non-ST elevation myocardial in arction (P), what is the e ect o in uenza vaccination at discharge (I) as compared to no vaccination (C) on recurrent acute coronary syndrome or mortality (O)?” An example o a properly designed clinical question about a diagnostic test is: “In patients presenting to the emergency department with suspected in ection (P), how accurate is a history o shaking chills (I), as compared a gold standard o blood cultures (C) in diagnosing bacteremia (O)?” When clinical questions do not per ectly t into the P-I-C-O ormat, clinicians should ollow as many o the above principles as possible.

■ STEP 3: CRITICALLY APPRAISING THE LITERATURE Although summary resources that appraise the medical literature have risen in quality and are an essential resource or clinicians, they will not always provide the answer to a clinical question. In addition, hospitalists may participate in discussions around particular studies, attend “journal club” con erences, or teach junior learners about evidence-based medicine. Hospitalists must have solid critical appraisal skills. The Users’ Guides to the Medical Literature (McGraw-Hill, 2014) is the benchmark textbook or learning how to practice EBM. It proposes an e ective method or critical appraisal that has been widely adopted. The principles and approach it endorses are discussed urther in this chapter. In appraising any type o study, three broad questions must be answered: 1. Are the results valid? 2. What are the results? 3. How can I apply the results to patient care? The critical appraisal process asks these three questions o each type o study, including those about therapy, diagnosis, 41

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TABLE 7-2 Hierarchy o Evidence or Di erent Types o Clinical Questions

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Di erential diagnosis o a condition

Best Types of Articles (Listed in Decreasing Level of Evidence) 1. Systematic review/meta-analysis o randomized controlled trials 2. Randomized controlled trial 3. Cohort study 4. Case-control study 5. Case series 6. Case reports 7. Expert opinion 1. Systematic review/meta-analysis 2. Prospective comparison against gold standard conducted in setting diagnostic test will be used in practice 1. Systematic review/meta-analysis 2. Prospective cohort study o a representative, homologous patient group with appropriate ollow-up and objective outcomes. 3. Retrospective case-controlled study 1. Systematic review/meta-analysis 2. Prospective evaluation o a representative sample that includes de initive diagnostic evaluation, per ormed in a setting similar to actual practice

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harm, prognosis, and systematic reviews. Each o the three major questions is answered through a subset o critical appraisal questions that are speci ic to each study type. The critical appraisal questions help determine i a study used proper methods to prevent bias, i the results are large enough to be meaning ul, and whether the results can be applied to a particular patient or population.

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Critical appraisal ocuses on answering three broad questions: Are the results valid? What are the results? How can I apply the results to patient care? The Users’Guides to the Medical Literature o ers a methodical approach to answering these questions or studies about therapy, diagnosis, harm, and prognosis, and or systematic reviews.

In recent years, a new type o evidence, the results o quality improvement studies, has risen in prominence. As hospitalists o ten are involved in quality improvement e orts, they should have a working knowledge o how to critically appraise this type o evidence. The Users’ Guides to the Medical Literature o ers urther instruction in this area. This chapter will illustrate the critical appraisal process through analysis o an article about therapy, as randomized controlled trials and prospective cohort studies are among the most common types o evidence encountered in practice. Table 7-3 outlines the critical appraisal questions, which are discussed in detail below. Clinicians should re er to the Users’ Guides to the Medical Literature or a complete list o critical appraisal questions or di erent types o research studies. 42

TABLE 7-3 Critical Appraisal Questions or an Article About Therapy Main Question 1. Is the study valid?

2. What are the results?

3. How can I apply the results to patient care?

Supplemental Questions a. Were patients randomized? b. Was group allocation concealed? c. Were patients in the study groups similar with respect to prognostic variables? d. To what extent was the study blinded? e. Was ollow-up complete? . Were patients analyzed in the groups to which they were irst assigned (ie, intention to treat)? g. Was the trial stopped early? a. How large was the treatment e ect? (What were the RRR and the ARR?) b. How precise were the results? (What were the con idence intervals?) a. Were the study patients similar to my patients? b. Were all clinically important outcomes considered? c. Are the likely treatment bene its worth the potential harm and costs? (eg, what is the number needed to treat? What is the number needed to harm?)

Adapted rom Guyatt G, et al., eds. Users’Guides to the Medical Literature: A Manual for Evidence-Based Clinical Practice, 3rd ed. New York, NY: McGraw-Hill Education; 2014.

■ CRITICAL APPRAISAL OF AN ARTICLE ABOUT THERAPY To critically appraise an article about therapy, the clinician should answer the ollowing set o questions. Are the results valid Were patients randomized? Randomization will best ensure that the intervention and control groups are equal at the start o the trial, except or the intervention being tested. In observational studies, investigators must take special steps to ensure experimental and comparison cohorts are evenly matched. Randomization does much o this automatically. Was group allocation concealed? When allocation concealment is present, those enrolling patients into the study during randomization are blinded to what group (ie, intervention or control) the patients are being assigned. Without allocation concealment, or example, a patient being enrolled but who is viewed as likely having a bad outcome might be steered into the comparison group, potentially improving the results in the intervention group. Were patients in the study groups similar with respect to known prognostic variables? This is necessary to isolate the e ect o the intervention and minimize con ounders. Proper randomization will ensure this. In the absence o randomization, clinicians should look to see that the intervention and comparison groups were care ully matched so as to be equal or all possible con ounders. This is o ten dif cult to do, which is why randomization is pre erred. To what extent was the study blinded? The term “doubleblind” does not describe all parties that should be blinded in an RCT. For maximum validity, multiple groups should be blinded,

What are the results How large was the treatment ef ect (ie, what were the relative risk reduction and absolute risk reduction?)? Clinicians should consider results o a study using the absolute risk reduction (ARR), where the ARR% = event rate in comparison group – event rate in experimental group. The relative risk reduction (RRR) is calculated as RRR% = event rate in comparison group – event rate in experimental group/event rate in comparison group. The RRR allows one to determine the e ect o a therapy on an individual patient according to their baseline risk. Consider the study by Sharma et al., published in the American Journal of Gastroenterology in 2013, that randomized 120 hospitalized patients with cirrhosis and overt hepatic encephalopathy to ri aximin versus placebo. In-hospital death occurred in 24% o the ri aximin group and in 49% o the placebo group. Here the ARR is 25% (49% – 24%) and the RRR is 51% (49% – 24%/49%). Clinicians can use the RRR to estimate the e ect a therapy will have on individual patients they treat that may be more or less sick than the average patient in a study. For example, i a patient is estimated to have a baseline risk o dying o 60%, ri aximin will reduce this patient’s risk o dying to 30.6% (60% × 0.51). In this case the ARR will be 60%-30.6% = 29.4% which is higher than what the ri aximin group as a whole experienced in the trial. In a similar way, lower baseline risk will result in lower absolute risk reduction.

H A P T E R 7

A randomized controlled trial describes the average e ect o an intervention across the group o patients studied. The e ect an intervention will have on any individual patient can be determined by combining that patient’s baseline risk with the relative risk reduction (RRR) reported in the trial. Clinicians can estimate their patient’s baseline risk by comparing them to the clinical characteristics and comorbidities o patients in a trial, and by using their clinical judgment and expertise.

c i p l e s o E v i d e n c e B a s e d M e d i c i n e a n d Q u a l i t y o E v i d e

Con dence intervals provide more in ormation than P-values alone, giving an estimate o the range o possible results. Some highquality evidence-based summary resources, such as ACP Journal Club, emphasize con dence intervals and the help ul picture they paint o the results. In the study o ri aximin described above, the RRR = 51% (95% CI, 20-71). In “plain English,” this 95% con dence interval tells us that ri aximin most likely reduces in-hospital death by 51% (the “point estimate”) but it may reduce in death by as little as 20%, or by as much as 71%. There is a 95% chance that the true e ect is between 20% and 71%, a 2.5% chance the true e ect is below 20%, and a 2.5% chance it is above 71%. In order to determine whether a trial has ound two therapies to be equivalent, clinicians should examine the upper and lower limits o the 95% con dence interval. I either would be clinically signi cant i true, the two therapies studied cannot be called equivalent, and urther research is needed. A 2014 study by Regimbeau et al. published in the Journal of the American Medical Association ound that in patients undergoing cholecystectomy or acute calculous cholecystitis, postoperative antibiotics reduced in ection by an absolute risk reduction o 1.9% (95% CI, –9.0-5.1, P < 0.05). The con dence interval indicates that antibiotics most likely reduce in ection by 1.9%, but may reduce in ection by as much as 5.1% (in which case most clinicians would prescribe them), or may increase in ection by as much as 9% (in which case most clinicians would not prescribe them). In this study, the true e ect o antibiotics on postoperative in ection could not be determined as they could be either bene cial or harm ul, and urther study is needed. A common misinterpretation o these results, which could occur i the con dence intervals are not noted, would be: “the P-value is greater than 0.05 so there is no di erence between antibiotics and placebo and the two are equivalent.” Two actors a ect the width o a con dence interval: the number o patients and the requency o the outcome in a study. In our example o the Regimbeau trial, urther studies that enroll larger numbers o patients or measure more postoperative in ections could result in a narrower con dence interval as well as a di erent point estimate.

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including those selecting patients or randomization (ie, allocation concealment), the patients, those administering the intervention, the data collectors/analysts, and the outcome assessors. When patients or those administering the intervention cannot be blinded (as in trials o certain surgeries or procedures), allocation concealment, as well as blinding o data analysts and outcome assessors, is essential. Was the ollow-up complete? Studies should track the outcomes o all participants. Patients may be lost to ollow-up i they su er a negative outcome or nd the intervention too dif cult to comply with. Both o these reasons would be highly relevant to the results o a study. Were patients analyzed in the groups to which they were rst assigned (ie, intention to treat)? The principle o “intention to treat” highlights that in a clinical trial, the o ering o an intervention to participants is being tested as much as the other e ects o the intervention. I or instance participants do not like the taste o a pill or nd a study protocol too hard to comply with and drop out o a trial or asked to be switched to the other arm as a result, these consequences must be recorded as part o the results o the study. Outcomes must be attributed to the group to which participants were initially assigned. A trial that ollows the intention to treat principle will give the best estimate o what will happen i a therapy is o ered to a population. In a “per protocol analysis,” the study results represent only what happened to those who actually accept the intervention and complete the trial. This type o analysis can in orm what e ect a therapy would have i taken properly by a highly compliant patient. Was the trial stopped early? Follow-up must be an appropriate length or the outcome measured. For example, 3 days might be an appropriate ollow-up period or an intervention to reduce acute pain, but it would likely be too short or an intervention designed to reduce LDL cholesterol or to improve unctional status. Randomized controlled trials that are stopped early because o bene t may overestimate the e ect o an intervention. A large bene t observed early in a trial may be due chance, and may be greater that what would be observed i the trial were allowed to run to completion.

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Con dence intervals are pre erable to P-values when considering the results o a clinical trial, as they give more in ormation about the range o possible results, including the best and worst case scenarios.

How can I apply the results to patient care Were the study patients similar to my patients? The more a patient meets the inclusion criteria, and the less they meet the 43

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exclusion criteria, the more con dently the results o a study can be applied to them. Clinicians should consider the setting o a study as well as whether those who administered the intervention had specialized expertise that is not available locally. Were all clinically important outcomes considered? The “grandmother test” can help determine i an outcome is clinically relevant. Outcomes that would be valued by the average person (eg, someone’s grandmother) are clinically important; outcomes that would not be valued are not clinically relevant and should not be measured by clinical trials. For example, outcomes such as a reduction in pain, an increase in survival, or a reduction hospital admission are likely to be meaning ul to patients, while biochemical, laboratory, or purely hemodynamic outcomes are not. An exception is when nonclinical outcomes are established surrogate markers or clinically important outcomes. Composite outcomes o clinical endpoints are valid, but i possible studies should make clear how much each individual endpoint is driving the composite result.

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The number needed to treat (NNT) describes how many patients must be treated with an intervention to produce one positive outcome or prevent one negative outcome. The NNT allows clinicians to compare the e ects o di erent therapies, and is calculated as NNT = 100/ARR%. In the study by Sharma et al. discussed above, inhospital death occurred in 24% o the ri aximin group and in 49% o the placebo group. Here the ARR is 25% (49% – 24%) and the NNT is 4 (100/25). In other words, we need to give our patients ri aximin to prevent one patient rom dying in the hospital. In order to best in orm risk/bene t discussions about a therapy, studies should measure important adverse e ects. The number needed to harm (NNH) describes how many patients must be treated or one to experience a particular adverse e ect. These two numbers can be compared or an intervention and a particular adverse e ect to determine the net bene t or harm. In addition to the likelihood o adverse events and their morbidity, the level o concern a patient has about particular side e ects must be considered. Many studies do not assess cost, and those that do o ten determine cost-e ectiveness at the population level, which is less relevant to the individual patient. The extent to which a therapy is covered by insurance is highly relevant to patients and should always be considered.

■ STEP 4: APPLYING THE LITERATURE TO AN INDIVIDUAL PATIENT For the ndings o a study to be use ul in clinical care, the critical appraisal process must yield a satis actory answer to each o the

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three broad questions discussed above: a study must be valid, it must report important results, and it must be applicable to the patient at hand. I any o these three elements is missing, the study ndings may not be appropriate or implementation into practice. When a study has used valid methods, has reported highly important results, and has enrolled patients clearly similar to the patient in question, the hospitalist can con dently apply its ndings. But conducting clinical studies is o ten dif cult work, and ew studies are per ect in every way. Clinicians need to learn which validity or applicability issues represent atal aws, and which ones still allow the results o a study to be considered. This is a skill that comes with experience. The hospitalist must remember that best evidence-based decisions incorporate not only the evidence, but also the individual clinical circumstances and pre erences o patients. In most cases, patient values and pre erences are more important than the other actors. CONCLUSION This chapter has ocused on skills such as the construction o ocused clinical questions and how to search and critically appraise the literature. These skills are necessary but not suf cient or the practice o EBM. The hospitalist’s knowledge o the patient is at the heart o evidence-based practice. The right clinical questions cannot be asked unless the hospitalist rst has a clear understanding o the patient’s clinical issues, and the literature cannot be applied to a patient without knowledge o their values and pre erences. Communication skills, history and physical examination skills, illness scripts, problem representation, and clinical reasoning skills are some o the ways hospitalists come to know their patients. To be a top-notch practitioner o EBM really starts and ends with being an outstanding clinical doctor.

SUGGESTED READINGS Devereaux PJ, et al. Double blind, you are the weakest link— goodbye! Evidence-Based Med. 2002;7:14-15. Guyatt G, et al., eds. Users’ Guides to the Medical Literature: A Manual for Evidence-Based Clinical Practice, 3rd ed. New York, NY: McGraw-Hill Education; 2014. Haynes RB, et al. Clinical expertise in the era o evidence-based medicine and patient choice. ACP Journal Club. 2002; March/April: A11-A14. Regimbeau JM, et al. FRENCH Study Group. E ect o postoperative antibiotic administration on postoperative in ection ollowing cholecystectomy or acute calculous cholecystitis: a randomized clinical trial. JAMA. 2014;312:145-154. Sharma BC, et al. A randomized, double-blind, controlled trial comparing ri aximin plus lactulose with lactulose alone in treatment o overt hepatic encephalopathy. Am J Gastroenterol. 2013;108:1458-1463.

CHAP TER

8

Diagnostic Reasoning and Decision Making Laurence Beer, MD, SFHM Lucas Golub, MD Dustin T. Smith, MD

INTRODUCTION Diagnosis is the art o identi ying a disease by the signs, symptoms, and test results o a patient. Diagnosis stems rom the Greek word, diagignoskein, which means to distinguish or discern. Indeed, the ability to distinguish or discern a patient’s underlying illness is critical to being an e ective clinician as a hospital medicine provider. In many cases, hospitalized patients may be quite complicated with multiple competing possible reasons to explain their underlying signs or symptoms. Patients do not always read textbook (ie, they may not always describe their symptoms or have ndings on exam that are pathognomonic or as classically described). There ore, diagnostic reasoning and diagnostic decision making are crucial skills or hospital medicine providers. In addition, cognitive biases exist and diagnostic errors occur when there is any mistake or ailure in the diagnostic process that leads to a misdiagnosis, a missed diagnosis, or a delayed diagnosis. This chapter will discuss diagnostic reasoning and diagnostic decision making.

DIAGNOSTIC REASONING

■ CLINICAL REASONING Clinical reasoning is the process where a clinician applies reasoning in combination with the clinician’s knowledge and skills (Figure 8-1). Clinical reasoning is a constant process that does not end when the diagnosis has been made. It may be considered complete upon autopsy or when a gold standard has con rmed a diagnosis, but it is important to acknowledge that in many instances the gold standard is not 100% accurate. In the hospital setting clinicians are operating under a running diagnosis until the diagnosis has been con rmed and/or until the patient has improved both subjectively and objectively. Sometimes patients do not improve when a treatment strategy is implemented; thus, it is important that providers continuously use clinical reasoning skills as in ormation is collected in an attempt to veri y the diagnosis. Once a treatment or workup plan has been implemented, it is crucial to reassess the patient’s response to this to urther con rm i the correct diagnosis or treatment strategy has been made (Figure 8-2). I the diagnosis does not appear correct or the treatment strategy is ailing, the clinician must review the in ormation and data collected and reconsider the other possible diagnoses to explain a patient’s presenting signs and symptoms. Hence, a clinician’s ability to success ully reason and diagnose is in some ways anchored by that clinician’s ability to create an adequate di erential diagnosis.

■ DIFFERENTIAL DIAGNOSIS A di erential diagnosis is more than just a list o illnesses that potentially explain why a particular sign, symptom, and/or diagnostic test result exists. Rather, the clinician uses the di erential diagnosis to distinguish a disease or condition rom others that present with similar signs, symptoms, or diagnostic test results. Initially start with a broad list o diagnoses until urther in ormation or data is obtained. A clinician must consider the prevalence o disease and other actors, which make up a provider’s patient population, when ormulating a di erential. It is more o ten the case where a common disease presents in an atypical ashion rather than a rare or exotic disease actually being present. 45

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is excluded. Once a diagnosis has been con rmed, the problem list should be diagnosis-oriented rather than problem-oriented. Should a patient not respond to a treatment plan or a diagnosis where a clear and obvious bene t is expected, the clinician should then re-evaluate the patient, review the data obtained, and nally provide a summary o key data to ensure that the diagnosis is indeed correct.

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A di erential diagnosis is the ability to distinguish a disease or condition rom others that present with similar signs, symptoms, or diagnostic test results.

List the top diagnosis rst but keep it problem oriented until the diagnosis has been made. Aggressively prioritize most likely then most harm ul in clinical workups. Exclude what diseases can easily be excluded and then remove those rom di erential diagnosis. Keep a broad di erential until the top diagnosis has been con rmed and always plan or workup o other alternate diagnoses i the top diagnosis is excluded. When presented with a clinical conundrum, begin by de ning the problem, be deliberate and gather key in ormation, and then nally summarize the case when aced with large amounts o in ormation.

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List your top diagnosis rst ollowed by other potential diagnoses or a speci c problem but keep it problem oriented until you have the actual diagnosis (eg, chest pain di erential diagnosis: most likely acute coronary syndrome but consider heart ailure, pneumonia, pneumothorax, pulmonary embolism, and musculoskeletal pain). Aggressively prioritize workup o the most likely and most harm ul (ie, li e threatening) diagnoses under consideration. Prioritize the workup o acute and reversible diseases ollowed by chronic and irreversible diseases (eg, delirium due to a medical cause versus chronic, progressive dementia). As in ormation or data that e ectively rules out a particular diagnosis or a chie complaint becomes available, remove that diagnosis rom your list and ocus your attention on remaining possibilities. Clinicians should always keep a broad di erential until the top diagnosis has been con rmed but also have a plan or workup o other alternate diagnosis i the top diagnosis

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Utilize illness scripts, which can be very power ul tools or clinicians and aid in diagnosis.

■ REASONING PROCESSES

(Re )As s e s s pa tie nt

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Illness scripts are made up o key risk actors, pathophysiology, and clinical presentations that summarize a speci c clinical problem or syndrome. An illness script can be a very power ul tool or clinicians. The number o illness scripts an individual clinician has increases with time and experience. Illness scripts may also diminish i a provider’s site o practice, specialty, or patient population becomes limited (eg, a clinician whose only site o practice is in a private hospital setting or adult hospitalized patients). An example o some commonly agreed upon illness scripts may be ound in Table 8-1.

The dual-process theory o reasoning consists o two systems o reasoning, which clinicians can utilize to correctly arrive at a diagnosis (Figure 8-3). The rst system is intuitive while the second system is analytical. A care ul balance o these two systems is necessary to ensure e cient and e ective clinical reasoning. Colle ct info

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Figure 8 2 The process of clinical reasoning. 46

Per orm the dual-process theory o reasoning and make sure to balance the intuitive and analytical components to maintain highly e cient and e ective clinical reasoning.

The rst system o the dual-process theory is intuitive, implicit or automatic. O ten an unconscious or subconscious process involving pattern recognition or matching against illness scripts markedly a ects the clinician’s judgment; the clinician’s past clinical experience and clinical expertise weighs heavily on this system. Heuristics, or mental shortcuts, are also utilized in this system.

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emergent abdominal surgery in childhood • More common in older children and adolescents • More common in boys

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• Obstruction o the vestigial

abdomen • Occurs most requently in second and third decades o li e • 1.4:1 male: emale

vermi orm appendix • In lammation o the appendiceal wall • Localized ischemia, per oration, and the development o a contained abscess or generalized appendicitis

H A P T E R 8 D i a g n o s t i c R e a s o n D e c

Acute appendicitis in children

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Abdominal pain, typically beginning in the periumbilical region and migrating to the right lower quadrant Anorexia Nausea or vomiting Low-grade ever Peritoneal signs on abdominal examination +McBurney’s point tenderness, Rovsing’s sign, ilopsoas sign, and/or obturator sign Mild leukocytosis Abdominal pain, typically right lower quadrant Anorexia Nausea or vomiting Low-grade ever Peritoneal signs on abdominal examination +McBurney’s point tenderness, Rovsing’s sign, psoas sign, and/or obturator sign

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media Hemorrhage into the media Creation o a alse lumen Propagation o dissection both distal and proximal to initial tear involving branch vessels, aortic valve, and/or pericardial space Ischemia, aoritic regurgitation, and/or cardiac tamponade Obstruction o the vestigial vermi orm appendix In lammation o the appendiceal wall Localized ischemia, per oration, and the development o a contained abscess or generalized appendicitis

Aortic dissection

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adults More requent in women Involved in activities that involve lexing or extending o wrist repeatedly (eg, typing a book chapter) Uncommon event Most common predisposing actor is hypertension Typically occurs in 60- to 80-y-old men

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Clinical Presentation Nonbilious projective vomiting In ant demands to be re ed soon a terwards No diarrhea Severe weight loss Emaciated with “olive-like” mass on abdominal exam Hypochloremic metabolic alkalosis Hypokalemia Pain and parasthesia in the medial nerve distribution Worse at night Changes in hand posture or shaking the hand mitigates symptoms + Phalen maneuver and Tinel test

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TABLE 8-1 Examples of Illness Scripts

Acute appendicitis in adults

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Strategies to avoid pit alls exist include:

Sys te m 1: a utoma tic, s ubcons cious proce s s ing EXP ERT HEURISTIC

• Always begin by de ning the problem a patient aces or reports. • Deliberate and gather key in ormation, as opposed to gatherDia gnos is

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The second system o the dual-process theory is the analytic, conscious and deliberate type o reasoning. The clinician uses rational and care ul analysis when evaluating a di erential diagnosis or a speci c problem. This system involves hypothesis testing as a tool or clinical reasoning (Figure 8-3).

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Numerous pit alls exist in clinical reasoning and practice. Clinicians may overly rely on heuristics, or mental shortcuts. Cognitive biases may alter a clinician’s judgment and clinical reasoning. In the modern era o clinical practice, in ormation overload and overreliance on diagnostic tests may lead to excessive testing or “overdiagnosis,” or the diagnosis o a “disease” that will never cause a patient symptoms or death. Certain diagnoses prompt treatments and interventions which may cause harm, especially i the alternative is best managed by watch ul waiting regarding the identi cation o an incidental nding or very early stage disease.

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In the modern era o clinical practice, in ormation overload is another pit all as is overreliance on diagnostic tests, which may lead to overtesting or “overdiagnosis”(ie, the diagnosis o a “disease”that will never cause a patient symptoms or death).

ing large amounts o in ormation. Per orm a summary o key elements in abstract terms to provide a discriminatory and use ul overview o the patient’s clinical case when aced with large amounts o clinical in ormation. This is o ten re erred to as problem representation. Utilize illness scripts which summarize a speci c clinical problem. Pay particular mind to not prioritize exotic or rare diseases initially or aggressive work-up (see base-rate neglect below). Always consider the diagnostic testing and treatment thresholds or the diagnoses he/she is considering in the di erential. Nonanalytic and analytic reasoning must be balanced, especially when a clinical pattern does not t a known illness script. Be cognizant o biases in clinical reasoning and avoid them at all costs. Always keep in mind that patients “do not always read the textbook.”

■ COGNITIVE HEURISTICS AND BIASES The worse heuristic comes rom the Greek word, heuriskein, meaning to nd or discover. Diagnostic decision making is ultimately a path toward discovery, requiring deliberate, systematic thought. There are many avenues o systematic approach to a common question, each with unique issues and pit alls. A summary o cognitive heuristics and biases with examples given can be ound in Table 8-2.

■ ANCHORING Anchoring bias arises when undue importance is placed on in ormation that is received early in the diagnostic evaluation. The clinician does not adjust the di erential diagnosis commiserate with the totality o in ormation as new, possibly contradictory data, emerges. The inverse o anchoring is known as the “order e ects” bias, where recent in ormation is given more weight in the decision process.

TABLE 8-2 Description of Cognitive Biases or Heuristics with Examples Bias or Heuristic Anchoring

Description Undue ocus on a case’s starting point, without adequate adjustment or new in ormation

Availability (recall)

Overestimation o diagnostic likelihood based on vivid or easily recalled events Impression that two diseases which present similarly are equally likely Pre erence or intervention over inaction Attempting to con irm a diagnosis rather than testing other possibilities Clinical decisions judged by the result rather than the logic o the choices Iatrogenesis is perceived to be worse than naturally occurring adverse events Early cessation o investigative thought once a presumed diagnosis has been made Patients do not read textbooks and pathology will not always present as expected An end to in ormation gathering once something has been ound

Base-rate neglect Commission Con irmation Hindsight Omission Premature closure Representativeness Search satis ying

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Example Patient with chronic obstructive pulmonary disease presents or dyspnea, does not improve with medical therapy, and is later ound to have a pulmonary embolism Suspicion o pheochromocytoma in a patient with chronic, resistant hypertension Overestimation o the probability o aortic dissection in chest pain Thrombolysis or submassive pulmonary embolus Leading (non open-ended) questions aimed at eliciting history which con irms a suspected diagnosis Use o bilevel ventilation is judged to be bene icial because the patient survived severe hypoxia Surgery not pursued or appendicitis and overwhelming sepsis because operative mortality is judged to be too high Altered mental status and ever are attributed to alcohol withdrawal, but aspiration pneumonia is also present Cholecystitis dismissed because Murphy’s sign is negative Rib ractures are not identi ied on a chest radiograph with in iltrate

■ AVAILABILITY

■ HINDSIGHT BIAS Hindsight bias or outcome bias may produce misguided positive eedback i inappropriate testing occurred but a positive clinical outcome resulted or negative eedback despite appropriate management i an adverse or unexpected outcome transpired. Knowledge o a case’s outcome may inf uence perception o preceding events.

■ OMISSION BIAS Primum non nocere ( rst do no harm). Omission bias occurs when clinicians do not therapeutically intervene because an adverse event resulting rom treatment is perceived to be worse than one due to inaction, even i the likelihood is exactly the same in both scenarios. Excessive emphasis is placed on avoiding iatrogenic harm.

■ PREMATURE CLOSURE Deliberate diagnostic consideration may be curtailed hastily i a presumed diagnosis is accepted be ore it has been completely established. Premature closure may occur either when a patient has multiple comorbid processes and the clinician xes on one or when the wrong diagnosis is made in the rst place.

■ REPRESENTATIVENESS Many diseases have a prototypical or “classic” presentation, and the probability o disease is o ten assessed according to how closely a speci c patient’s case mirrors that ingrained portrait o the disease in question. This search or representative presentations will miss atypical variants o common disease. It also predisposes clinicians to dismiss diagnostic possibilities because a cardinal eature is absent, even i that eature is not necessarily present in all cases.

■ SEARCH SATISFYING Search satis ying describes the cessation o in ormation acquisition once something has been ound. This heuristic is di erent rom premature closure in that it applies to eatures beyond the primary diagnosis. With clinical ocus on this, other subtle eatures may be missed including additional comorbidities, subtle lab abnormalities, and radiologic ndings that do not t with the reason or presentation.

C H A 8 D i a g n o s t i c R e a s o n i n g a n d D e c i s i

Health care sa ety and quality researchers have borrowed concepts rom other high-risk industries like the military, aviation, and nuclear power generation that have proven success ul at minimizing adverse outcomes. Situational awareness re ers to having a keen awareness o the multitude o environmental actors that inf uence decision making in complex, dynamic situations. Having broad situational awareness acilitates understanding o what is happening, why it is happening, and anticipating what is likely to happen next, making it easier to identi y problems at an early stage, be ore they become catastrophic. The concept o situational awareness may be used to mitigate the types o errors engendered by both the limitations and complexity o hospital medicine and by the complex organizational and systems structures that de ne modern hospitals. Sources o error due to the nature o hospitalist work include lack o long term relationships with their patients and knowledge o their prior level o unctioning, incomplete medical histories, large volumes o rapidly changing and sometimes conf icting data, polypharmacy, and misperception o disease prevalence due to a particular hospital’s demographics. Systems-based sources o error, which in one study are present in two-thirds o all errors, include discontinuities in care, lapses in communication, and lack o coordination between departments. Explicit acknowledgement o and extra attention to both sources o error can elucidate ways in which the individual clinician and the institution as a whole may decrease error. Increasingly, hospitalists are working on wards organized as Accountable Care Units (ACUs). ACUs by de nition are structured around shared missions and goals, and are ideal organizations or the implementation o group-based situational awareness techniques. In this ormulation, team members are expected to operate rom the same script, share a common knowledge base and language, anticipate the needs o other team members, and be

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Con rmation bias is the inclination to seek in ormation that conrms the current clinical assessment rather than delving into alternative hypotheses. Con rmation bias may aggravate anchoring and thereby cause a vicious cycle that hampers diagnostic momentum.

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Both individual skills can be developed and systems-based practices can be instituted to minimize diagnostic error and improve diagnostic reasoning. Individual skills that may be taught include situational awareness, deliberate practice, and metacognition. Systems-based solutions include creating a process or providing individual eedback, developing a nonpunitive error reporting culture, the use o electronic medical records, and urnishing computer-based decision support tools. A summary o cognitive debiasing strategies can be ound in Table 8-3.

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PRACTICE POINT

TABLE 8-3 Cognitive Debiasing Strategies to Improve Clinical Reasoning Situational awareness Error reporting and accountability Deliberate practice Feedback Decision support tools and other electronic-based systems Metacognition

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able to adapt to tasks as they arise. All team members, regardless o role on the team, are taught to recognize “red f ags” such as eeling con used, having a gut instinct that something is wrong, sensing that other team members are overlooking important in ormation, or observing improper procedures. They are then empowered to bring these concerns to the attention o the rest o the team without ear o reprimand.

Web-based morbidity and mortality con erences, interactive medical cases, clinical conundrums, and other real-time tools have largely replaced eedback rom autopsies and morbidity and mortality con erences. Case simulations and standardized patients, a now common eature o medical training programs, also present opportunities or trainees to receive real-time eedback.

■ DECISION SUPPORT TOOLS AND OTHER Electronic decision support tools (DSTs) include order sets, electronic health record (EHR) embedded alerts and reminders, quality metric dashboards, web-based di erential diagnosis engines (eg, ISABEL and DXplain), and clinically oriented literature review resources such as UpToDate and Epocrates. All o these have the potential o guiding physician behavior toward evidence-based practice (and away rom anecdotal, bias-driven practice). Data regarding the e ectiveness o DSTs, except in very speci c domains such as medication dosing, or in institution-speci c applications, is mixed. One metaanalysis ound that DSTs modestly improve morbidity but have no e ect on adverse events or mortality. Conversely, DSTs did seem to improve adherence to preventative care guidelines and ordering clinical studies. There are no rigorous examinations o the potential negative e ects o using DSTs. Nonetheless, DSTs provide a resource that is more ree rom the cognitive biases that inf uence much o physician clinical practice and may provide the occasion or a clinical “time-out” (Table 8-2). EHRs themselves are an o t-overlooked orm o DST. By collating and organizing large volumes o data, well-designed EHRs acilitate diagnostic ref ection, enhance collaboration, and provide a means or receiving eedback. Increasingly, EHRs are also including elements o data analysis such as the ability to graph lab values over time.

■ DELIBERATE PRACTICE

Metacognition is de ned as “thinking about thinking.” It involves sel -questioning and ref ecting on personal biases and assumptions. It implies an active, rather than an automatic, control o the thinking process. Examples o metacognition include planning how to approach a cognitive task (eg, diagnosis) and how to evaluate progress in that task. Several authors have suggested the use o a diagnostic checklist (Figure 8-7) to prompt metacognition.

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Rote practice (ie, expertise in any ield requires a minimum o 10,000 hours o practice) is not su cient. Instead, goal-directed, care ully measured, deliberate practice (ie, ref ective practice) is also required. Without deliberate practice the mere accumulation o experience leads to a plateauing o clinical skills and in some cases even a decline as previously acquired knowledge is orgotten. Deliberate practice is a training method that ollows the iterative cycle o planning, per ormance, and ref ection. The planning phase consists o goal setting, sel -motivation, and orientation toward learning. The per ormance stage consists o time-management, care ul record-keeping, benchmarking, and seeking out expert assistance and direction. The ref ective phase consists o sel -evaluation and studying shortcomings and ailures. One review o research on deliberate practice ound that trainees should be given tasks with clearly de ned goals, motivated to improve, provided eedback as soon as practically possible, and given numerous opportunities to re ne their skills. Experts engaged in deliberate practice consciously seek out clinical challenges just beyond the current skill level o trainees. Properly modeling such habits or trainees allows them to become more sel -motivated, sel critical, and able to engage in li e-long improvement.

■ FEEDBACK Without eedback, it is impossible or clinicians to properly calibrate their sense o diagnostic accuracy leading to both over- and undercon dence. Overcon dence has been identi ed as a requent cause o diagnostic error. Feedback should be real time, speci c, and coupled with corrective instruction. 50

ELECTRONIC-BASED SYSTEMS

In order to learn rom medical errors clinicians must rst and oremost be encouraged to report them. Accomplishing this requires the care ul cultivation o a nonpunitive culture in which team members are reed rom ear o reprisal. In order to urther de-stigmatize medical error and create a climate o transparency clinicians are now being encouraged and in many institutions required to report medical errors to their patients. These progressive views o error do not mean that clinicians should not be held accountable or their errors, but rather that examination o errors should be or the purposes o quality improvement rather than punishment. Since many errors are at least in part due to f awed systems or a breakdown o multiple processes, an appropriate apportionment o responsibility between the hospital, clinician, and ancillary sta is warranted. In act, due to their presence throughout the hospital, hospitalists are uniquely positioned to encounter, understand, and report on systems-based errors. To get the most in ormation about medical errors hospitals should not only employ anonymous error-reporting systems, but should actively solicit cases o medical error rom their sta . I these errors are not obvious because no substantial harm was caused or because the patient nonetheless recovered, they might not otherwise be reported. Even the reporting o “near-misses,” in which a potential error is identi ed be ore it is actually committed, should also be encouraged.

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■ ERROR REPORTING AND ACCOUNTABILITY

■ METACOGNITION

DIAGNOSTIC DECISION MAKING

■ BEDSIDE DIAGNOSIS Bedside diagnosis with a comprehensive history and physical exam continue to orm the bedrock o clinical medicine despite the astronomical technical innovations o modern medicine. It is impossible to ully interpret even the best diagnostic testing without a thorough prior knowledge o the patient. The adage that “ninety percent o the diagnosis is in the history” remains true, even in the 21st century. For example, the di erentiation o stable and unstable angina (not to mention cardiac rom noncardiac causes o chest pain) requires a skilled clinician at the bedside and carries dramatic therapeutic implications.

■ DIAGNOSTIC TESTS AND INTERVENTIONS Some diagnostic tests are better screening tests or disease whereas others are better con rmatory tests. Some diagnostic tests are power ul enough to screen and con rm disease. Many laboratory tests do not simply report a positive (presence o disease) and negative (absence o disease) but rather a range requiring application o the result to speci c patients. For example, a very low brain or B-type natriuretic peptide (BNP) level (eg, >> risk); the

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the intervention as highly recommended. • Desired bene ts more closely balanced with any undesirable e ects, given only marginal bene t upon initial study.

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evaluation o very limited patient populations resulted in only a “C” grade or level o evidence. Likewise, a recommendation may be considered o low strength i the treatment e ect or bene t-risk ratio is very small and still considered o high level o evidence i multiple populations have been studied and results have proven to be both certain and precise. Repeated studies are less likely when the ollowing occurs:

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certainty behind the recommendation. The strength o a recommendation may be a ected by numerous actors but generally is a representation or the size o treatment e ect and degree o bene t versus risk or a speci c intervention. Some interventions may have an un avorable risk-bene t pro le and thus would receive a recommendation strength denoting the risk is greater than the expected bene t. Some interventions shown to be o no bene t may be classi ed as such.

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■ APPLICABILITY Clinical practice guidelines that are use ul must be applicable to a clinical provider’s patient population and clinical scope o practice. The practices and recommendations described in guidelines must be able to be replicated by clinical providers in their own practice in order or them to be relevant and worthwhile. Additionally, actors such as disease prevalence, risk actors, comorbidities, and individual patient pre erences that di er rom the target population rom which the guidelines were developed may a ect the applicability o the guidelines to di erent patient populations. Conf icting guidelines or discordant recommendations may be made by di erent organizations such a venous thromboembolism prophylaxis in subpopulations (eg, orthopedic surgery). Clinicians may not be able to reconcile discordant recommendations or every occasion. Tools are available to acilitate guidelines comparisons so that clinicians may determine the quality and applicability o guideline to speci c patient populations. One example o a tool that exists to aid clinicians is the “Compare Guidelines” tab that exists at www.guideline.gov sponsored by Agency or Healthcare Research and Quality. The simplest and most appropriate approach should always take into account individual patient risk actors, health care pre erences and goals o care. Be ore o ering interventions (including screening) and therapies to patients, always ask the question: “Do these clinical practice guidelines apply to my patient?”

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Practice guidelines provide three important bene ts or hospital medicine providers by acilitating consistency, e ciency, and e ectiveness to improve health care outcomes. Similar to high-quality recommendations rom a consultant, practice guidelines should give clear recommendations, discuss alternatives, acknowledge biases, and consider extenuating circumstances or a speci c clinical case. A modi ed ramework or hospital medicine providers to use in both interpreting and assessing the quality o clinical practice guidelines is divided into three general domains with subdomains: M Validity: scope and purpose, group composition, conf icts o interests, literature review, group processes, external review and endorsements, editorial independence, and current guidelines M Results: strength o recommendations and level o evidence M Applicability

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There are our major overviews, and they include narrative reviews, systematic reviews, meta-analysis, and guidelines. They represent the highest quality o evidence on the quality pyramid as they synthesize evidence rom many sources. Narrative reviews elucidate a health context, condition, or intervention. They tend to answer background questions, biologic, or social issues. However, the methods or article inclusion and quality assessment are not structured and the credibility o the review is tied to the reviewer expertise. Systematic reviews and meta-analyses may ocus on therapy, diagnosis, or prognosis depending on the clinical question at hand. Table 10-1 highlights the similarities and major di erences between the various types o overview articles. The goals o systematic reviews include answering questions where conf icting data exist and/or where sample sizes o individual trials are small. The ultimate goal o systematic reviews may be to generate hypotheses. Meta-analyses are a type o systematic review that use quantitative methods to combine results rom multiple studies to yield a summary estimate o e ect and a con dence interval around the estimate. A common source to search or systematic reviews and meta-analyses is the Cochrane Database (http://www. cochranelibrary.com/).

■ DEFINE THE QUESTION Whereas in narrative reviews the clinical question tends to be more general, the clinical question in systematic reviews should be ocused in a ormat with a clearly de ned patient population, intervention, control, and clear outcomes. An example would be: “What is the risk o bleeding in adult patients with recurrent venous thromboembolism on rivaroxaban as compared to war arin?”

■ LITERATURE SEARCH Because the goal o systematic reviews is to synthesize in ormation rom many sources, it is important that a thorough review o the literature is done to prevent missing relevant studies. There should be a discussion o the bibliographic databases searched with the search terms included. The search strategy and included databases will depend on the question being asked. There should be an attempt to locate unpublished studies such as con erence abstracts, experts in the eld, pharmaceutical companies, and investigators o studies. There should also be consideration to searching in languages 66

besides English based on prevalence o diseases in certain countries. Consideration o these actors can reduce the potential or publication bias, which may produce misleading summary e ects.

■ INCLUSION AND EXCLUSION CRITERIA In systematic reviews, inclusion and exclusion criteria or articles should be stated and there should be a discussion o the patients included, the exposures or interventions, the outcomes o interest and the methodological standards or study selection (eg, randomized controlled trials, diagnosis cohort, or observational studies). To improve the quality o studies, i randomized controlled trials exist, then these should be used pre erentially to minimize bias. There should be speci c inclusion and exclusion criteria based on the clinical question such as patient demographics (eg, age, sex, ethnicity, etc).

■ QUALITY OF STUDIES There should be an assessment o individual studies that are included in the systematic review. For therapy studies, there should be evaluation or randomization (ie, allocation concealment), blinding (o investigators, patients, data collectors), and loss to ollow-up as these can introduce systematic error in the meta-analysis. Ideally, the studies should report intention-to-treat (ie, all patients who underwent allocation are analyzed regardless o how long they stayed in the study) or per protocol (ie, only patients who remained within the protocol or a predetermined period are analyzed). For diagnostic studies, there should be evaluation o the appropriate re erence standard. Typically in systematic reviews, there should be quality assessment by more than one individual and investigator other than the principal investigator o the review. There are several ways to assess or the quality and di erences amongst the individuals making the quality assessment. The kappa statistic (κ) represents the interreviewer reliability and is a measurement o the agreement between observers beyond chance. The κ-value ranges rom –1.0, which is no agreement, to 1.0, which is per ect agreement. For most studies, a κ-value o 0.8 or higher is acceptable and represents excellent agreement and a κ-value o less than 0.4 represents poor agreement. The Jadad score is another structured way o assessing the quality o individual studies. The score is based on upon points or randomization, double blinding, and withdrawals. Table 10-3 shows the modi ed Jadad scoring template or randomized controlled trials. The Newcastle-Ottawa score can be used or nonrandomized controlled trials.

■ META-ANALYSIS I it seems reasonable and suitable, data rom several studies can be combined to give an overall estimate result. The overall results produced rom the results o a larger number o patients than individual studies are more accurate and reduce type 2 error (ie, ailing to detect a di erence that exists between the two groups), which increases the power o the analysis. It is important that the results can be appropriately combined (ie, individual studies have similar interventions, patients, outcome measures); otherwise, it would be like the popular idiom: “combining apples and oranges.” Data in meta-analyses are presented as Forest plots. There are various statistical methods used to combine di erent data types, which will be discussed later in this chapter.

■ POOLED ESTIMATESAND FOREST PLOT Figure 10-1 shows an example o a orest plot produced or a metaanalysis. On the le t side, the names o the individual studies are listed. The green box represents the individual data rom the studies and the risk ratio (with 95% con dence interval) is calculated taking

S tudy o r s ubg ro up Bla ck 2004 Dolittle 1999 Finlay 1999 Higgins 2001 Le ctor 2000 S tra nge love 2005 Wa ts on 2005 To tal (95% CI) Tota l eve nts

In meta-analyses, publication bias may o ten be present. Results with signi cant positive ndings are more likely to be submitted and accepted or publication. This phenomenon leads to an overestimate o treatment e ects. Publication bias may be evident rom comparing results rom published versus registered trials, published studies versus doctoral dissertations, and randomized trials versus observational studies. Studies with signi cant positive results are likely to generate multiple publications, hence propagating the bias. Researchers rom countries where English is not the major spoken language may tend to submit nonsigni cant results to their own respective domestic journals. Searching or articles published only

Ris k ratio Expe rime ntal Co ntro l Eve nts To tal Eve nts To tal We ig ht M–H, Fixe d 95%CI 3 6 15 4 24 17 12 81

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1.38 [0.25, 7.53] 1.02 [0.36, 2.88] 1.45 [0.71, 2.93] 0.76 [0.22, 2.65] 1.89 [1.03, 3.49] 1.64 [0.83, 3.24] 2.34 [0.90, 6.04]

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He te roge ne ity: Chi2 = 3.09, df = 6 (P = 0.80); I2 = 0% Te s t for ove ra ll e ffe ct: Z = 2.78 (P = 0.005)

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into account the weight o the study. The weight (ie, importance in the overall result) is based on the sample size and precision o the results. More weight is given to studies with a larger sample size and a smaller standard deviation. The orange box shows the pooled data and risk ratio. The absolute risk di erence and number needed to treat or harm can also be calculated rom this gure. In this example meta-analysis, the total experiment event rate is 0.25 and the control event rate is 0.16. Thus, the approximate risk ratio is 1.57 ( avors control), absolute risk increase is 0.09, and the number needed to harm in this case is 11. Whereas many o the individual studies are small and not statistically signi cant, when pooled together, the overall e ect becomes statistically signi cant with a narrower con dence interval. The right side o the graph shows the individual mean e ect as a dot with the line representing the 95% con dence interval. The larger the dot, the larger the weight it is given to the overall result. The diamond represents the overall e ect size, and the size o the diamond is dependent on the 95% con dence intervals. A larger and/or wider diamond implies larger con dence intervals and a low

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Figure 10 1 Example of a forest plot in a meta-analysis. 67

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in English adds to publication bias. A unnel plot is used to assess or the presence o publication bias in a meta-analysis. As shown in Figure 10-3A, a plot o the sample size (or standard error) versus the e ect size (relative risk or risk ratio) is made. Each dot represents the overall e ect rom one randomized controlled trial. The larger the sample size is (or smaller the error), then the higher the dot on the graph is placed. The dotted red line shows the overall estimate and i there are no missing studies, then the results should be located in a symmetric, triangular area centered on the overall e ect o all studies. I there are missing studies as in seen Figure 10-3B, then they will appear as a gap in the portion o the unnel plot where one would expect to nd negative studies. The unopposed positive studies will shi t the apparent treatment e ect (blue line) toward a larger size than it really is.

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There are two statistical models used to combine the results rom multiple studies in a meta-analysis: the xed-e ects model and the random-e ects model. Each model has advantages that inf uence interpretation o results. A xed-e ects model assumes there is a single true value underlying all o the study results. All the studies should give identical estimates o the e ect i all o the studies addressing the same question are large and ree o bias. Variance in this model is derived only rom within-study variance and does not incorporate between-study variance (ie, heterogeneity). A xed-e ects model generally gives more weight to larger studies with narrower con dence intervals. This model may be reasonable when there are a small number o studies

included or a meta-analysis or when one large study may be more trustworthy than smaller studies with di ering results. A random-e ects model assumes that the studies include a random sample o the population o studies that address the question in the meta-analysis. Because there are di erences in patients, interventions, and outcomes in the studies, each study estimates a di erence underlying true e ect that has a normal distribution. The pooled e ect in the random-e ects model is not a single e ect but a mean e ect across populations, interventions, and outcomes. This model takes into account both within-study variance as well as between-study variance (ie, heterogeneity). In the random-e ects model, large studies with wider con dence intervals have more weight. The random-e ects model is generally considered the more reliable approach o the two models. Figure 10-4 highlights some o the di erences in these two models. In Figure 10-4A, both models yield a similar net estimate when there is no heterogeneity. However, the xed-e ects model yields tighter con dence intervals compared to the random-e ects model, which is a more conservative estimate o the overall e ect, when there is similar sample size in each study but variability between studies as in Figure 10-4B.

■ SUBGROUP AND SENSITIVITY ANALYSIS Subgroup analyses are o ten presented in systematic reviews to determine i certain groups o patients may respond to treatment as compared to other groups (eg, patients more or certain comorbidities versus patients with less or no comorbidities). While these subgroup analyses may help individualize treatment, they must be interpreted with caution. A ew principles or critical questions

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The next question asks i the results may be applied to a speci c patient and/or patient population now that it has been determined that the systematic review and meta-analysis answers the original clinical question, that there was an appropriate search or the evidence and an assessment o the quality o the evidence, and that the study results were appropriate to combine. This step requires consideration o all clinical outcomes as well as the bene ts versus the harms and costs. Evidence-based medicine relies not only on the best evidence available but also clinical expertise, clinical experience, and patient pre erences. Clinical experience improves the e ciency o diagnosis and treatment, expands the ability to determine the applicability o research data to the individual patients, and allows or the consideration o patient pre erences. First ask the question: “Do these results apply to my patient?” whenever considering o ering interventions and therapies to patients based on data rom systematic reviews and meta-analyses.

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A sensitivity study may also be per ormed in a meta-analysis i there are relatively lower quality data used. It may re er to a comparison o analyses using the random-e ects model versus xede ects model. Alternatively, it may re er to the use o quality scores o included trials to modi y the impact o lower quality studies to the overall result o the analysis. Although this may reduce the contribution o lower quality studies, there may be bias because it allows authors to somewhat arbitrarily reduce the e ects or dismiss the e ects o studies they may not like.

Atkins D, Best D, Briss PA, et al. Grading quality o evidence and strength o recommendations. BMJ. 2004;328:1490. Brouwers MC, Kho ME, Browman GP, et al. Development o AGREE II, part 1: per ormance, use ulness and areas or improvement. CMAJ. 2010;182:1045-1052. Brouwers MC, Kho ME, Browman GP, et al. Development o AGREE II, part 2: assessment o validity o items and tools to support application. CMAJ. 2010;182:E472-E478. Guyatt GH, Oxman AD, Kunz R, et al. GRADE: an emerging consensus on rating quality o evidence and strength o recommendations. BMJ. 2008;336:924-926. Irwig L, Tosteson AN, Gastonis C, et al. Guidelines or meta-analyses evaluating diagnostic tests. Ann Intern Med. 1994;120:667-676. Jadad AR, Moore RA, Carroll D, et al. Assessing the quality o reports o randomized clinical trials: is blinding necessary? Controlled Clin Trials. 1996;17:1-12. Moher D, Cook DJ, Eastwood S, et al. Improving the quality o reports o meta-analyses o randomized controlled trials: the QUOROM statement. Quality o Reporting Meta-analyses. Lancet. 1999;354:1896-1900. Murad M, Montori VM, Ioannidis JA, et al. Understanding and applying the results o a systematic review and meta-analysis. In: Guyatt G, Rennie D, Meade MO, Cook DJ, eds. Users’Guides to the Medical Literature. 3rd ed. New York, NY: McGraw-Hill; 2014;471-490. Neumann I, Aki EA, Vandvik PO, et al. How to use a patient management recommendation: clinical practice guidelines and decision analysis. In: Guyatt G, Rennie D, Meade MO, Cook DJ, eds. Users’ Guides to the Medical Literature. 3rd ed. New York, NY: McGraw-Hill; 2014;547-560. Qaseem A, Forland F, Macbeth F, et al. Guidelines International Network: toward international standards or clinical practice guidelines. Ann Intern Med. 2012;156:525-531.

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Does chance explain the subgroup di erence? Is the subgroup consistent across studies? Is there a biologic plausibility supporting the subgroup e ect? Is the subgroup di erence suggested by meta-analysis comparisons within rather than between studies?

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to help guide in determining the credibility o subgroup analysis include:

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Meta-analysis provides a quantitative, pooled estimate o a treatment e ect. Key advantages o a meta-analysis are that it can pool smaller studies yielding a larger sample size as well as summarize disparate data. Systematic reviews and meta-analyses are subject to publication bias, which can lead to some studies being missed and thus not included in the analysis. Bias in individual studies will lead to bias in the systematic review and meta-analysis. The nal conclusion should be based on the evidence, rather than personal opinion.

• Agency for Healthcare Research and Quality (AHRQ) National Guideline Clearing House. http://www.guideline.gov. • American Medical Association, JAMAevidence. http://jamaevidence.mhmedical.com. • Cochrane Collaboration, Cochrane Library. http://www. cochranelibrary.com. • Guidelines International Network (G-I-N). http://www.g-i-n.net. • The Appraisal of Guidelines for Research and Evaluation Enterprise. http://www.agreetrust.org. • The Grading of Recommendations Assessment, Development and Evaluation (GRADE) Working Group. www.gradeworkinggroup.com. 69

11

CHAP TER

Practical Considerations o Incorporating Evidence into Clinical Practice J. Richard Pittman, Jr., MD Mikhail Akbashev, MD

INTRODUCTION With over 21.5 million unique articles and more than 1 million randomized controlled trials indexed in MEDLINE as o 2014 and more than 1 million new publications published and indexed annually, clinicians now must process a vast volume o medical literature. Many clinicians eel like they are drowning in in ormation. Hospitalists must balance the need to nd relevant and accurate answers to their clinical questions with the need or e ciency in nding those answers to immediately guide high-quality care to multiple acutely ill patients. Formulating and answering questions e ciently and e ectively will improve care and reduce the rates o consultation, testing, and potential errors. The volume o data and limited time or searching or answers compound each other. A recent systematic review examining clinical questions raised by clinicians at the point o care ound approximately one clinical question arises or every two patient encounters. Clinicians only pursued 51% o the questions raised and ound answers to only 78% o those questions pursued. Studies reported the main barriers to seeking in ormation included a clinician’s lack o time and a doubt that a use ul answer existed. The state o relying on in ormation already known prevails when the energy required to get a new answer outweighs the perceived bene t. Clinical inertia may be illustrated by considering the gap between the potential bene ts o evidenced-based care and actual rates o implementation as in the treatment o heart ailure with reduced ejection raction (HFrEF). Optimal implementation o strong evidence-based therapies or HFrEF could save an estimated 35,000 to 117,000 thousand lives per year. See Chapter 129 (Heart Failure). In an ideal practice setting, the majority o clinical questions would have a readily accessible, evidence-based answer. Clinicians would have current knowledge o guideline-based therapy and could apply pertinent point-o -care reminders rom the electronic medical record or best practice or every patient under their care. As a result, patients would yield maximal bene t rom clinical trials and guideline-driven in ormation. This ideal state may not be attainable; however, clinicians may take steps toward better utilizing the evidence-based answers currently available to meaning ully impact clinical practice. CURRENT CONSEQUENCES AND MOTIVATORS FOR CHANGE

■ PRACTICING WITH OUTDATED INFORMATION Relying on outdated in ormation or patient care (ie, clinical inertia) may limit potential bene ts o current therapies and expose patients to risks o disproven therapies. An example would be practicing based o outdated guidelines or the treatment o blood cholesterol to reduce atherosclerotic cardiovascular disease (ASCVD) risk in adults where a clinician tailors treatment and statin dosing based solely on the low-density lipoprotein cholesterol (LDL-C) levels rather than selecting a moderate- or high-intensity statin strategy based on ASCVD risk, an LDL-C ≥ 190 mg/dL, and/or the presence o diabetes as recommended in the current updated guidelines.

■ UTILIZING UNVERIFIED INFORMATION SOURCES Clinicians may utilize unveri ed in ormation sources. Examples o possible unveri ed in ormation sources include seemingly more in ormed colleagues, television programming/advertisements, 70

• Preset, reliable stream o

• • • •

in ormation lowers the energy required to incorporate new in ormation into clinical practice, leaving a clinicianless subject to clinical inertia or anchoring. Many o the tools are ree and can ocus on a speci c discipline or a topic. The volume o in ormation presented can be adjusted based on clinician desire or tolerance. The requency o the delivery o this in ormation can be customized. Article summaries by colleagues trained in evidence-based analysis can be accessed and can raise awareness o potential inclusion biases.

Disadvantages include: • These streams may become overwhelming i the amount

and requency o content is not properly customized to the individual clinician pre erences. There is a risk o attending

C H A P T E R 1 1 P r a c t i c a l C o n s i d e r a t i o n s o I n c o r p o r a t i n g E v i d e n c e i n t o C l i n i c a l P

Solutions should take into consideration how a clinician might encounter in ormation during the f ow o practice. “Keeping up” with the literature is increasingly di cult, and staying abreast o important developments that may not directly relate to patients that the clinician is actively managing. “Keeping up” single-source publications rom an area o clinical ocus are use ul, but they may narrow a clinician’s awareness o broader advances across di erent disciplines. There are numerous methods to “keep up” with the literature that transcend traditional postal mail by utilizing e-mail or designated applications or mobile devices. Users sign up or these “keeping up” resources as reputable and reliable evidence sent to them rom trusted sources. These tools may help clinicians keep up with a particular eld or topic by organizing in ormation by discipline, relevance to that discipline, and newsworthiness or impact level. This in ormation may be delivered to an e-mail inbox, a website, or to a discrete mobile application. The ocus below will be on ree resources available or those included with pro essional society memberships common or most hospital medicine providers. Advantages o push resources available or most hospital medicine providers include:

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SOLUTIONS TO INCORPORATE EVIDENCE INTO CLINICAL PRACTICE

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Perhaps the strongest and most important motivator or change should be the act that evidence- or guideline-based practice has been shown to improve patient outcomes across a wide spectrum o illnesses.

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■ EVIDENCE-BASED PRACTICE IMPROVES PATIENT

1. Setting up digital resources. It may be help ul or a clinician to initially take consider what in ormation he or she needs and the areas o knowledge de ciencies (eg, original research manuscripts, clinical updates, and guidelines). Any individual clinician may not be aware o each o her or his personal de ciencies, especially since “blind spots” are by de nition not seen. Thought ul attention to one’s knowledge base, de ciencies, and practice gaps may lead to crucial rst digital steps or change. In addition, a comparison o pro essional needs and knowledge gaps should be made with regards to any resources a clinician is actively subscribed. A busy clinician should pay care ul attention to cutting down on in requently used resources prior to subscribing to new ones. Consideration should be made or an individual clinician’s pre erred method o receiving in ormation. Some like in ormation to come straight to their e-mail with a link to a website while others pre er opening a designated application on their device(s). E-mails clutter e-mail inboxes, but most people regularly check e-mail. Mobile applications clutter your devices while also continuing to collect new material unnoticed to the clinician. This can be corrected by removing unused applications that clutter mobile devices while also taking steps to become amiliar with how applications work and aggregate in ormation. Most tools discussed in this chapter strive to deliver in ormation in a way that best ts the workf ow o di erent clinicians (Table 11-1). The key is or any individual practitioner to identi y resources most convenient and reliable or that individual clinician. Once an account is setup or the any o the resources, the next step is to select specialty and topic pre erences. Once these steps are completed, the in ormation will then be sent either via e-mail or to a mobile application depending on which resource is selected (Figure 11-1). A critical step is to then monitor the use ulness o in ormation and then a ter a period o time (eg, a couple o weeks or a month) go back into the tool and adjust the settings or unsubscribe rom the resource based on its help ulness or not. 2. Schedule time or new reading. A seemingly simple step, but one that can make a large di erence in “keeping up” is to schedule time or new reading. Carrying a paper or virtual le with articles, presentations, and/or books may make a hal an hour be ore rounds, between appointments, or while sitting in carpool lines a lot more productive. 3. Attend institutional con erences. Attending institutional con erences (eg, Grand Rounds, noon con erences) is an excellent way or a clinician to acquire new in ormation while also providing the opportunity to spark conversations and clinical questions with colleagues. Volunteering to present a topic at con erence promotes expertise acquisition o new and updated clinical knowledge. 4. Participate in pro essional societies and their scientif c meetings. Scienti c meetings hosted by medical pro essional societies are designed to help clinicians stay abreast o the ever-changing in ormation and also to o er credit or Continuing Medical Education. 5. Encourage a culture o learning. Activities such as journal club, case con erence, and clinical updates in hospital medicine at hospitalists’ sites o practice can be an e ective way to

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Depending on a clinician’s com ort level with evidence-based medicine and available search tools and time, a clinician may only read article summaries or conclusions rom abstracts. This represents a orm o search satis action bias. When an answer is ound to a clinical question that is requently encountered in a clinician’s scope o practice, the clinician might jump to apply this answer to all subsequent patients without ully assessing the validity and quality o the source or considering the applicability o this in ormation to the individual patient.

Suggestions

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■ SEARCH SATISFACTION BIAS

a con erence or reading a publication on mobile resources that may be tempting to clinicians to sign up or too many resources at one time. • Selection methodology or choosing the articles presented may not always be clear.

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popular media, drug company representatives, and searching or “evidence” or answers to clinical questions using search engines that may provide in ormation rom unveri ed sources (eg, “Googling”). Heavy reliance on unveri ed in ormation sources can signi cantly limit the quality o in ormation with which a clinician practices and should be avoided i possible.

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pertinent to the patient, with speci c, actionable in ormation that is quickly and reliably accessed. Unlike the “keeping up” resources previously discussed, these “quick questions” need to be answered or a real patient right now. That is why using these types o resources is essential in day-to-day patient care. Fortunately, multiple resources exist including current textbooks, database search tools such as Trip Database, popular portable resources such as UpToDate or Dynamed, and large databases like PubMed. These resources have been developed to answer speci c, patient-related questions. Hospitalists should check with their institutional subscriptions rst and utilize these be ore personally enrolling in subscriptions that may be expensive. Developing “quick questions” require clinicians to stop their f ow o work and look or an answer. Cumbersome retrieval o in ormation may lead to clinical inertia. Initial searching using summary resources, such as textbooks or review articles, can be e cient and more likely to yield pertinent answers. However, these resources are subject to authorship biases. Important articles could potentially be omitted while smaller studies maybe overly emphasized in recommendations. Summary resources can also be delayed in incorporating the most recent study results, even sometimes those o large pivotal studies. Many clinicians start with a Google search with Wikipedia as the top listed initial resource. This may o ten be a quick and satis ying way to answer simple medical de nition questions such as “what is an antimitochondrial antibody.” Mainstream publicly available search engines such as Google or Yahoo can o er ast and ree searches but o ten are less reliable and may not provide a robust and accurate answer to clinical questions as would more rigorously vetted medical resources, such as AccessMedicine, ClincialKey ( ormerly MD Consult), DynaMed, Medscape (a.k.a. eMedicine), UpToDate and a growing list o other compiled medical summary resources and reviews (Table 11-2). These resources have made incorporation o new in ormation a priority.

TABLE 11-1 Example Digital Resources or “Keeping Up”

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E-mail/Website-Based BMJ Evidence Updates

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ACP Journal Club NEJM Journal Watch PubMed—My NCBI

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Application-Based (App) Docphin Read by QXMD

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Website Link https://plus.mcmaster.ca/ evidenceupdates/ http://annals.org/journalclub.aspx www.jwatch.org http://www.ncbi.nlm.nih.gov/ pubmed/ Website Link

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promote a culture o learning, which can help providers urther keep up with the f ow o new in ormation. 6. Utilize the electronic health record. Perhaps the most pertinent time to receive updated in ormation on any treatment or diagnostic test is at the time o ordering the treatment or test. Recent advances and expansions in electronic health records (EHR) o er a limited opportunity or “just-in time” learning about speci c medical concepts. Many EHRs incorporate evidence-based recommendations into order sets, as well as linking users to literature regarding updated recommendations. A recent meta-analysis showed improvement in both e ciency and adherence to guidelines through use o EHR. Similarly, a study o an older computer support tool or antibiotic management ound a dramatic decrease in pharmacy antibiotic expenditures and mortality rates over a 6-year period. A systematic review o 68 controlled trials o computer decision support systems ound the majority o the trials demonstrated bene t in physician per ormance and patient outcomes. Multiple health systems have implemented quality improvement projects to adhere to core measures using order sets within the EHRs with great success.

Suggestions Despite the apparent limitations, actively and e ciently searching or answers to clinical queries is an essential part o patient care. Overcoming clinical inertia to identi y and explore questions is the rst step. This may be as simple as an index card with questions or the day or lunches with colleagues to discuss cases. Having identi ed questions, a clinician needs to ormulate the question as speci cally as possible and identi y an e cient search strategy (Figure 11-2).

■ QUICK QUESTION The context is essential or any clinical question. The ideal “quick question” resource would be readily available at the point o care,

Newsworthine s s 5

*Ale rt cut off s core s Re leva nce 6

To s e e how ma ny a rticle s you a re like ly to re ce ive a t va rious leve ls of re leva nce a nd newsworthine s s, try cha nging the leve ls a bove, the n look a t the gra ph be low. At the curre nt cutoffs s hown a bove, on ave ra ge you would ha ve re ce ive d 9 a rticle s pe r month in the la s t 12 months

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Figure 11 1 Screenshot of BMJ evidence updates. This is an example of a free online “keeping up” resource which allows users filter paper alerts by topic, relevance and newsworthiness, to narrow to a manageable amount. 72

Yes

Collection o evidence-based summary reviews on common clinical topics; presented in bulleted ormat with speci ic citations and assessment o evidence quality or recommendations. Systematic rapid inclusion o newly published high-quality evidence, including systematic reviews

Yes

Search engine to browse guidelines and systematic reviews; integrated with other resources such as calculators, coding helper, or decision support tools

Yes

Wiley Medscape (a.k.a. eMedicine)

Compilation o summaries by specialists in the ield; includes new article ormats

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WebMD PubMed Clinical Queries

Indexed database o articles rom a multitude o medical journals

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Automated evidence search engine o primary studies, guidelines, textbooks and other clinical resources with ilters available; scores articles based on how recent, pertinence, and publication source

No

Evidence-based online textbook. Compendium o expert written invited reviews on a broad array o topics; evidenced based and graded recommendations, primarily prose and directive in nature

Yes

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Automated evidence search engine, allow users to search the primary medical literature, guidelines and standard textbooks

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CME Yes

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Description Compendium o rapidly searchable medical textbooks

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TRIP Up To Date

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NIH TRIP Database (Translating Research Into Practice)

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TABLE 11-2 Example Digital Resources or Answering Clinical Questions

Wolters Kluwer

Many hold to dogma and use PubMed as an initial search. This o ten yields a time-consuming search, with many published articles to si t through, and challenges nding relevant studies e ciently. This also has been shown to take 41% longer (29 vs 17 minutes) than UpToDate searches in a cohort o resident physicians. Furthermore, a study o 54 medical students, residents, and aculty searching multiple methodologies to answer critical-care-related questions showed that users most requently searched Google rst (45% o the time), with Google and UpToDate providing aster answers than PubMed (3.8 vs 3.3 vs 4.4 minutes, respectively). Importantly, Google and UpToDate were more likely to lead to a correct answer than PubMed (60% vs 70% vs 36%, respectively). The highest value rst resource is o ten a compiled resource such as Dynamed or UpToDate, but multiple resources are available rom various publishing organizations (Table 11-2). Regardless o the initial search strategy, there are o ten clinical situations that require more nuanced answers and speci c expertise.

These questions should be very concrete and speci c. A standard “PICO” (Patient, Intervention, Comparison, Outcome) ormat identi es the pertinent parts o a question (eg, “What is the e ect o 23-valent pneumococcal polysaccharide vaccine versus placebo on mortality in patients with systolic heart ailure exacerbations?” or “What is the relative risk o bleeding with rivaroxaban versus war arin in patients with venous thromboembolism?”). For questions too speci c or narrow to be ound in summarized resources, a primary literature search may be pre erred. PubMed o ers ree access to users, and its “Clinical Queries” search option quickly lters results or clinical and systematic review articles. Other electronic resources like TRIP (Translating Research into Practice) database can quickly lter studies indexed in MEDLINE, guidelines and other resources, and it also ranks them on quality and type o study. Guideline searches may be completed through the National Guideline Clearinghouse (http://www.guideline.gov), which is a resource maintained by the U.S. Department o Health and Human Services. This resource 73

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Is This a Co mmo n To pic ? • Would the re be g uide line s for this ? • Am I unfamiliar with this topic?

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Primary Lite rature S e arc h: • Pubme d clinica l que rie s review a rticle s • Trip da ta ba s e • Cochra ne da ta ba s e • Othe rs

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Figure 11 2 An effective search strategy for answering clinical questions.

acilitates comparison o guidelines on topics published rom di erent societies (eg, breast cancer screening guidelines rom American College o Physicians versus American College o Obstetrics and Gynecology). Although somewhat cumbersome to use initially, it is readily updated. Actively recruiting clinical trials are indexed in the registry ClinicalTrials.gov (https://clinicaltrials.gov), provided by the U.S. National Institutes o Health. Although there are advantages and disadvantages to the di erent resources, the least use ul resource is the unavailable resource. For this reason, clinicians should nd the resources available at their home institutions. Clinicians should identi y clinical questions and explore the available resources to nd answers. Ideally, a query should obtain a high-quality answer in less than 5 minutes.

■ STORAGE FOR FUTURE REFERENCE A challenge o the digital and increasingly paperless work environment is how to keep up with the materials that an individual clinician would like to save or uture re erence. Mobile technology can really help take busy clinicians ar beyond the traditional physical le cabinet into a system that can travel on mobile devices with certain ones that can even help create bibliographies i needed. Many digital storage solutions ollow the “ reemium” model. “Freemium” is a pricing strategy that re ers to an initial ree price or the limited use o an application that then tiers to paid subscriptions or heavier use. The real advantage o the digital storage solutions is their use o storing les virtually in the “cloud.” The “cloud” re ers to the storage o les in a server (ie, high-capacity computer) that 74

is connected to a clinician’s personal computer or mobile device via the Internet. The advantages o this include an online backup and the ability to synchronize les across multiple devices with very little e ort. Many o these services allow a clinician to keep a copy o the les on a computer or mobile devices so these les can be accessed even when not connected to the Internet. These systems retrieve in ormation by storing text documents that can be searched using terms that obtain results based not just on the title o the le but also rom the text o the document. This allows use o these resources with almost no organization necessary. With a digital storage solution, the important tactile experience o touching and annotating the original article is lost. The clinician must convert rom paper to digital les, name olders, and move documents to the olders that have been created. A similar e ort would be required to set up a new le cabinet, but many struggle to invest the time into a similar digital system. Theoretically, this digital storage solution is still a mechanical system that could ail. Suggestions 1. Understand the cloud Many clinicians already have user accounts or cloud-based storage solutions but are simply unaware that they do. Programs such as Dropbox, Google Drive, Box, Evernote, OneDrive, and iCloud all meet the de nition or cloud-based storage solutions. I a clinician already has one o these accounts, then it may be best or that clinician to rst explore all the eatures o that solution, be ore considering others (Table 11-3).

Microso t Onedrive

Free up to 7 Gb

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15 Gb ree, paid plans or 100 Gb per mo

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Google drive

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3. Comp ly with p atient conf dentiality As with any new developments or advances in technology that a ects or modi es a clinician’s practice, care should be taken to assure the sa ety and protection o a patient’s con dentiality. Most cloud resources are not compliant with the Health Insurance Portability and Accountability Act (HIPAA). As such, patient or personal health in ormation should not be stored on these digital and cloud-based drives. The notable exception is “enterprise services” provided by the digital plat orm Box,

o n s o r a t i n g E v i d e n c e i n t o C l i n i c a l P r a c t i

4. Annotate articles Some clinicians pre er to read paper articles, which then allows or highlighting or annotating. Digital versions o these articles o ten allow o highlighting or annotating as well depending on the viewer used on a computer or mobile device. This latter way o reviewing articles allows the clinician to more easily save notes taken right inside the cloud-based storage solution being used. For those who still pre er the paper version to initially review an article, clinicians should consider document scanner to convert the annotated paper version o the article into a digital one which can then be stored in these cloud-based storage plat orms. The scanner that uses “Optical Character Recognition” or OCR to turn the documents scanned into a text searchable document a ter storage provides optimal unctionality. At the time o this chapter being dra ted, Evernote is the only one o the cloud-based solutions that has annotation (eg, highlighting) or drawing built into its system. Many o these other plat orms can integrate easily with so tware/application viewers or readers (eg, “Portable Document Format” or PDF) which are available on most mobile devices.

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2. Use cloud-based storage A ter gaining an understanding o the “cloud,” clinicians should strongly consider using cloudbased storage in their practice. In general, any o these cloud-based storage solutions will work to get started, so once a choice is made regarding which one to use then time must be invested by users in order to learn how to use all o the eatures. Many have “getting started” videos which can be viewed on their respective websites. Once a clinician is amiliar with the tool, time should be set aside or at least an hour or two to allow or some les or articles to be moved over to the cloud olders. Investing time up ront will allow a busy clinician to get the most o out o the system and generally be better organized moving orward in clinical practice. Choosing a system-based organization (eg, cardiology, gastroenterology, in ectious diseases, and so on.) versus by more speci c topic areas (eg, heart ailure, cirrhosis, pneumonia, and so on.) depends on the le contents and personal pre erences o the individual clinician. The next time a clinical question comes up about the topic previously searched and saved in this storage system, the clinician can simply check the system rather than doing another search.

but it should be noted the “personal service” o Box is not HIPAA compliant.

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While the solutions can be accessed through websites using a web browser, most also o er applications that can be downloaded and placed on personal computers and mobile devices that allow or more convenient access o their stored les. The applications work by turning les and olders meant or storage into ones that are automatically synchronized and immediately uploaded to the cloud, which allows them to thereby be available rom anywhere.

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Ideal i heavy user o Microso t ® O ice, especially on a windows plat orm computer

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Accepts multiple types o inputs including audio, photos, scanned documents, and web clips; advanced organization with notebooks and tagging Best or working on iles with other users, even simultaneously; great i you use Android mobile device(s)

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Cons Web editing, commenting, and tagging have some laws that limit their use ulness

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Cost/Memory Pros Free up to 10 Gb, then $10/mo or Only solution that advertises HIPAA 100 Gb complaint or enterprise clients; great amount ree; can edit documents on web, make comments, and assign tasks to documents Free up to 2 Gb, $10/mo Established company; cross plat orm with 1 Terabyte o storage easy sharing and well-integrated into mobile devices

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TABLE 11-3 Example Cloud-Based Storage Solutions

■ CULTURAL CHANGE Fostering a culture o education, accountability or actions, and support or evidence-based, high-quality care can encourage all clinicians to keep learning or better patient care. Although intangible personal attributes contribute greatly to culture, leadership can adjust policy to achieve desired outcomes by nurturing a workplace o collaboration, learning, open eedback, and accountability. A supportive, collaborative environment encourages clinicians to discuss individual studies or publications, treatment decisions on complicated cases, and even to work together on quality improvement and system-based projects. Impediments to collaboration among hospitalist groups include provider scheduling and workload. Seven-day-cycled schedules may isolate providers to those other providers on or the same shi ts only. Potential interventions to improve collaboration could include standardized work schedules, physician lounges, physician ca eterias, grouped o ces, and consideration o patient census caps. 75

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Open eedback also plays an important role in incorporating evidence and improving patient care. Increasing isolation o physicians and high workload limits the available time to discuss the management o individual patients and/or to ollow up on subsequent care while o -service. Hando s could be an opportunity or colleagues to review care and potentially noti y providers o updates in hospital medicine or new literature. In order to be success ul, this should be done in a collegial manner with adequate time allotted. Hospitalists should be encouraged to both give and request eedback regularly. Morbidity and mortality con erences may also o er an opportunity to discuss updates in new literature using a pertinent clinical case. “Word o mouth” spread o in ormation is a pertinent and power ul way to share medical in ormation and encourage a culture that strives to keep up with the literature.

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The volumes o literature and increasing demands on physician time have complicated the process o nding and incorporating evidence into clinical practice. Multiple new methods exist to receive new evidence on pertinent topics in manageable volumes. Compiled review resources are signi cantly quicker and more reliable initial resources than primary literature searches or most clinical questions. Cloud-based storage options o er the advantages o better search-ability and portability over ling cabinets and stacks o printed manuscripts and journals; most cloud storage options are not HIPAA compliant but are good or storing medical re erences. Simple steps can be taken to oster a positive learning culture at a hospitalist’s respective institution (eg, starting a journal club or scheduling lunchtime discussions o current topics). Some hospitalists may pursue resources to better keep up, while others may inquire at their institution or “quick question” resources. Some clinicians may already be inundated with what they have collected and need to invest in a cloud-based resource to decrease the stress every time they ask, “Where is that article?” Encouraging a work culture shi t toward addressing gaps may help clinician scope with in ormation overload. Even the most current or seemingly up-to-date clinicians started one step at a time and invested continued e ort.

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SUGGESTED READINGS Banzi R, et al. Speed o updating online evidence based point o care summaries: prospective cohort analysis. BMJ. 2011;343:d5856. Campanella P, et al. The impact o electronic health records on healthcare quality: a systematic review and meta-analysis. Eur J Public Health. pii:ckv122 [Epub]; Jun 30, 2015. Del Fiol G, et al. Clinical questions raised by clinicians at the point o care: a systematic review. JAMAIntern Med. 2014;74:710-718. Elliott DJ, et al. E ect o hospitalist workload on quality and e ciency o care. JAMAIntern Med. 2014;174:786-793. Hunt DL, et al. E ects o computer-based clinical decision support systems on physician per ormance and patient outcomes: a systematic review. JAMA. 1998;280:1339-1346. Kronen eld MR, et al. Survey o user pre erences rom a comparative trial o UpToDate and ClinicalKey. J Med Libr Assoc. 2013;101:151-154. Michtalik HJ, et al. Impact o attending physician workload on patient care: a survey o hospitalists. JAMAIntern Med. 2013;173:375-377. Rangachari P, et al. Awareness o evidence-based practices alone does not translate to implementation: insights rom implementation research. Qual Manag Health Care. 2013;22:117-125. Sayyah EL, et al. To compare PubMed Clinical Queries and UpToDate in teaching in ormation mastery to clinical residents: a crossover randomized controlled trial. PLoS One. 2011;6:e23487. Thiele RH, et al. Speed, accuracy, and con dence in Google, Ovid, PubMed, and UpToDate: results o a randomised trial. Postgrad Med J. 2010;86:459-465.

ONLINE RESOURCES • Society of Hospital Medicine’s learning portal at https:// shmlearningportal.org • Table 11-1 Digital Resources

SECTION 3 Transitions of Care

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Care Transitions into the Hospital: Health Care Centers, Emergency Department, Outside Hospital Transfers Joanna M. Bonsall, MD, PhD Stacy Higgins, MD, FACP Melissa B. Stevens, MD

INTRODUCTION For patients being admitted into the hospital, hospital admission may be the rst and most signi cant care transition that they will experience in their medical care. The number o inpatients being cared or by their primary care physicians has decreased signi cantly in the last several years. In a study reported in JAMA in 2009, outpatient to inpatient continuity with a primary care physician decreased rom 44.3% in 1996 to 31.9% in 2006, correlating with the growth o hospital medicine during the same time period. As a result, patients are requently cared or by physicians who are meeting them or or the rst time in the hospital, and who are un amiliar with their medical history, past hospitalizations, or amily and social support network. In addition, due to the “shi t” structuring o many hospital medicine groups, patients are likely to be cared or by multiple physicians during a single hospital stay, each one having to learn anew the subtleties o their history. Patients may be admitted to the hospital through the Emergency Department (ED), directly rom an outpatient o ce, or trans erred rom an outside acility such as another hospital, a Skilled Nursing Facility (SNF) or a Subacute Rehabilitation Facility (SAR). While these transitions have much in common, they also have unique challenges in care transitions that are speci c to their sites. We will discuss these challenges as well as potential solutions here. ADMISSIONS FROM THE EMERGENCY DEPARTMENT The majority o unscheduled admissions to the hospital come through the Emergency Department. The American College o Emergency Physicians estimates that over the past decade the percent o admissions through the ED has increased rom 64% to over 80% while at the same time there was a decline in the percentage o unscheduled admissions rom clinics or doctor’s o ces. Patients admitted through the Emergency Department experience two transitions—the transition into the ED and the transition rom the ED into the hospital. As patients’ transition rom the ED to the hospital the need to not only trans er in ormation but also to clari y who is primarily responsible or the patients’ care is critical as there is o ten a delay between the exchange o in ormation and the physical relocation o patients. Admissions that occur during shi t changes may be particularly problematic as they result in multiple trans ers o in ormation and responsibility. In the ED, patients may be admitted at a shi t change with data pending rather than be signed out to a new ED provider. These transitions can result in ambiguity and con icting expectations between ED providers and hospitalists speci cally regarding patient care responsibilities and can contribute to dropped in ormation, delays in treatment, and other errors that threaten the sa ety o patients. Strategies to improve the transitions are discussed below and outlined in Table 12-1.

■ TRANSITION OF INFORMATION Hospitalists and ED physicians have varied expectations o the ED to hospital handof both in terms o the in ormation that should be communicated and the data that should be available at the time o admission. ED physicians and hospitalists have dif erent roles in patient care and dif erent in ormation needs, which may lead to erroneous assumptions and misunderstandings. Understanding the actors that af ect care o patients and communication on both sides is crucial. Fatigue and increased workload can impact 79

TABLE 12-1 Strategies to Improve ED to Hospital Transitions

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1. Vital signs should be rechecked at regular intervals while patients are boarded, consistent with protocol or their intended loor location. 2. Orders written in the emergency department (ED) should be readily available or hospitalists to review in the electronic medical record (EMR). 3. Formalized structured eedback should immediately occur when there is an adverse event or hando miscommunication. 4. Standardized hando tools including an admission check-list should be used to set expectations. 5. Clearly delineate the responsibility or ollow-up o pending tests results. 6. Minimize asking EM physicians to order additional tests be ore patients are accepted or admission or trans er to the loor unless the tests will alter bed acuity level. 7. Clearly identi y the clinician o record. 8. Hospitalist changes o shi t or boarded patients should be communicated to ED sta expediently. 9. Responsibilities or boarded patients should be speci ied at the institutional level with written policy. 10. Prioritize getting boarders out o the ED to their inpatient units.

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communication and updating o patient in ormation and contribute to unintended outcomes. In order to improve sa ety and quality o care and avoid ambiguity hospitalists and ED providers at any acility should clearly identi y and mutually agree upon a minimum set o data elements that should be part o the transition. The use o checklists and standardized communications tools are recommended in assisting this process. In keeping with existing guidelines, the minimum data set should include a principle diagnosis and problem list, medication list, patient’s cognitive status, and test results/pending tests. In ormation should be communicated between providers in a secure, private and HIPAA compliant manor. Communication o in ormation should be done in person or by phone with an opportunity or both the admitting and receiving provider to ask questions and get clari cation and eedback. This last step, while recommended or all handovers, is especially crucial in this type o transition, given the dif erent backgrounds and roles o the providers. While hospitalists requently ask or additional in ormation to help with patient management decisions, such requests may lead to a delay in patient trans er. Requests or additional workup prior to admission may be appropriate i this in ormation will af ect one o the ollowing: (1) the level o inpatient care (ie, ward vs telemetry unit vs ICU), (2) the admitting service (medicine vs surgery vs other), or (3) time to obtain critical in ormation (ie, the patient may be able to get a CT more rapidly in the ED than once they are admitted to the oor). In the event that additional workup is warranted prior to a patient being accepted or admission, the ED provider and hospitalists should have a protocol or communicating in ormation about the patient at shi t change with their colleagues who will be responsible or ollowing up these tests and ultimately admitting these patients.

■ TRANSITION OF RESPONSIBILITY Unlike other transitions, the exact moment o the trans er o responsibility or patient care may be ambiguous. When patients are admitted rom the outpatient clinic setting or skilled nursing acilities, it 80

is clear that the admitting provider is responsible or the patient while they remain at their acility and once the patient leaves the admitting acility they become the responsibility o the accepting provider. However, patients do not typically leave the ED immediately a ter they have been accepted or admission by the hospitalist, leading to con usion on the part o patients, nurses and other staf as to who is responsible or the patient’s care. The ED provider and hospitalist should identi y pending labs and studies and who will be responsible or ollow up and communication o results. In the event that patients remain in the ED or any length o time a ter the communication o in ormation between the ED provider and hospitalist, there should be an established protocol or identi ying the responsible provider to be contacted with any new test results, question/concerns, or any change in the patient’s clinical condition.

■ PROLONGED ED BOARDING ED overcrowding and inadequate inpatient capacity lead to prolonged ED boarding and increased risk o harm not only or admitted patients but or ED patients as well. Admitted patients boarded in the ED do not receive the same level o care as they would on an inpatient unit and studies have shown that prolonged ED boarding is associated with an increase in preventable adverse events, length o stay and mortality. Institutions should develop a clear plan or standardized communication and trans er o responsibility o patients with prolonged ED boarding that should include a plan or shi t changes and may include standardized order sets to be initiated in the ED prior to trans er to an inpatient unit. Reducing ED boarding is a challenge at most acilities that requires the input o a multidisciplinary team. Prolonged ED boarding is usually the result o hospital overcrowding and there are many possible strategies to improve patient ow including: using a “ ull capacity protocol” where the burden o boarding patients is shared between the emergency medicine and hospital medicine department; coordinating discharges as early in the day as possible; moving toward a 24/7 operational culture, active bed management/ hiring a “Bed Czar” to match bed needs to resources and utilizing observation units.

■ COMMUNICATION BETWEEN THE PCP AND THE HOSPITALIST Barriers in communication between the primary care provider (PCP) and the ED physician or admitting hospitalist are similar on admission and discharge. On admission, patients may be in pain, con used, and distressed, providing limited or unreliable histories. The communication with the PCP can provide in ormation on past medical history, past hospitalizations, previous testing done, medication reconciliation, social history, and the baseline medical status o the patient. However, conversations require identi cation o the PCP by the patient, ability to reach the PCP in a timely ashion, easy access by the PCP to the patient’s updated medical record, and a mutually available time or the conversation. System barriers interrupting this communication include inadequate reimbursement to the PCP or the time involved in reviewing the record and the conversation; time shortage in a busy outpatient schedule; and ragmented patient care with an incomplete record. There is also the transition process barrier o the lack o a standardized communication system—success ul completion o a single phone call may require multiple calls in each direction as neither party is available at the time o the phone call, and lengthy waits between calls; text pages may not be responded to until records are reviewed and there is time in the schedule; and e-mails may not be secure and do not allow or interactive dialogue. In cases where the hospitalist and primary care physician share a common electronic health record, communication through the EHR

• The admitting diagnosis is airly certain and no additional triage

is needed. • The patient is clinically stable in their vital signs and does not require supplemental oxygen, immediate IV uids, antibiotics or urgent imaging. • The patient has been seen and evaluated on the day o admission by their primary provider. • The patient arrives at the hospital early in the day (be ore 4 pm) to acilitate communication between the admitting physician and the hospital team and be ore shi t changes. I the admitting hospital team is concerned about the patient’s condition or need or more extensive initial workup a ter getting

C H A P T E R 1 2 C a r e T r a n s i t i o n s i n t o t h e H o s p i t a l : H e a l t h C a r e C e n t e r s , E m e r g e n c y D e p a r t m e n t , O u t s i d e H o s p i t a

Advantages to admitting a patient directly to the hospital include convenience to the patient, improved patient satis action, reduced crowding o the Emergency Department, and decreased cost to the system. In evaluating who is appropriate or direct admission, there are a ew recommendations in the literature:

rom the PCP’s o ce to the hospital can save the patient hours o waiting in the ED and can help reduce ED overcrowding. However, patients appropriate or direct admission should be selected care ully, and clear communication between the PCP and hospitalist should occur. Institutions should partner with admitting PCPs to develop a checklist to determine whether a patient is appropriate or direct admission, and standardize what in ormation should be transmitted and how that in ormation should be transmitted.

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■ SELECTION OF APPROPRIATE PATIENTS

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While ewer patients are being admitted directly rom a physician’s o ce to the hospital, there are signi cant advantages to continuing this practice or appropriate patients. A direct admission means the patient can avoid the potentially long wait in the ED and prolonged ED boarding while also reducing ED overcrowding. The direct admission process also allows the opportunity or the PCP to speak directly to the hospitalist, sharing the patient’s medical history as well as providing some anticipatory guidance to the hospitalist, who is not as amiliar with the patient. However, as with all transitions, the direct admission has some speci c risks that need to be anticipated and managed. First, the patients appropriate or direct admission should be care ully selected, to ensure that they will be admitted to the correct care location and that they are not at risk or deterioration be ore being seen by the hospitalist. Second, there should be clear communication between the PCP and the hospitalist regarding the patient to be admitted.

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As with ED-to-hospitalist communications, primary care providers and hospitalists have dif erent patient care roles and perspectives, which may contribute to misunderstandings and missed in ormation. Opportunities to improve care at this transition can likely improve the experience o the hospitalized patient, reduce unnecessary testing, reduce length o stay, and potentially reduce cost to the system. On admission, as with all care transitions, there should be a minimum shared data set that should include the rationale or admission, the working diagnosis, the problem list, key history components and recent changes, relevant laboratory and radiologic results, medication list and allergies, and patient/ amily pre erences and support system. Ideally this in ormation should be shared both verbally and in a written ormat in a HIPAA compliant manor. Verbal conversations allow the hospitalist opportunities to ask questions and clari y in ormation. As the “accepting” hospitalist may not be the hospitalist who ultimately cares or the patient, the in ormation should also be in an accessible paper or electronic ormat or uture providers to re erence. This may be sent with the patient or sent by ax. Alternatively, the receiving hospitalist may ll out an electronic template during or a ter a phone conversation; however, this may be cumbersome. On initial contact, agreeing upon how, when, and under what circumstances urther communication should occur between in and outpatient physicians should be established.

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■ TRANSFER OF INFORMATION

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due to dif ering backgrounds/roles o providers and ambiguity at the time o admission about trans er o responsibility or patient care. To minimize the risk, ED and hospital medicine groups should develop mutually agreed upon in ormation checklists or standardized templates to aide trans er o in ormation; and should develop clear guidelines around who will assume responsibility or pending test results and changes in patient status in the period a ter the patient has been accepted by the hospitalist but still remains in the ED.

■ ADMISSIONS/TRANSFERS FROM OUTSIDE HOSPITALS

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signout, they can advise against a direct admission. Familiarity and trust between the outpatient and hospitalist group can help acilitate direct admissions as each learns the other’s practice style and com ort. While a patient may initially be assessed as stable or direct admission, an extensive wait time in patient registration where the patient is unmonitored or may miss scheduled medications may lead to the patient becoming unstable. As the number o inpatient beds is reduced, and the ll rate goes up, patients may have to wait several hours be ore receiving a bed assignment. Solutions include having a Care Initiation Unit that serves as a transition zone where the patient can check in, have their vital signs checked, and be evaluated by the admitting hospitalist there. This decreases time spent in the ED and catches patients who may need stabilization prior to going to the oor bed. It also allows or continuous monitoring and initiation o orders while awaiting a bed assignment.

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can be secure and timely, with ongoing real time access by both parties. However, this is likely the exception rather than the rule, and it assumes that patients obtain all o their care within a single health system. Where this does not exist, methods such as e-mail and ax are acceptable. With the growth o the Patient Centered Medical Home, it is possible that care coordinators in the health care system can help to acilitate in ormation trans er rom the medical home to the admitting physician. Employment o nurse case managers by practices can assist with the barrier o communication coordination, have access to the patient’s medical record, and can standardize the trans er o in ormation.

While trans ers rom outside hospitals account or a minority o hospital admissions (3%-5%), trans erred patients typically have a higher severity o illness and are more medically complex. Additional risks present at time o trans er o ten include a medical record system that is not shared with the trans erring hospital and delays in trans er due to transportation, distance rom receiving hospital, bed availability and physician acceptance, resulting in more than two-thirds o patients arriving at the accepting acility at night. While studies 81

TABLE 12-2 Risks of Interhospital Transfer During Transfer Decompensation during trans er Arrival at night Arrival to inappropriate level o care

After Transfer Discontinuity o care plan Unnecessary and/or duplicative testing Medication errors Back-end discontinuity

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Prior to Transfer Delays in care initiation due to lack o expertise Delays in care due to delays in inding an accepting acility Inappropriate trans er

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have shown improved outcomes or disease-speci c trans ers such as myocardial in arctions and trauma, in general, trans erred patients have overall higher levels o morbidity and mortality; these dif erences cannot always be accounted or by severity o illness alone. There ore, although only a minority o patients go through a transer, special attention should be paid to this care transition. Reasons or trans er typically include disease-speci c interventions not available at the trans erring institution and availability o subspecialty expertise at the receiving institution. However, reasons or trans er can also be less well-de ned and include lack o bed availability at the sending institution, patient request, and insurance coverage reasons. Medicaid patients continue to be trans erred at a higher rate than those covered by private insurance. Most studies on interhospital trans ers have ocused on disease-speci c reasons or trans er such as patients requiring percutaneous angioplasty or myocardial in arctions, trauma patients, or stroke patients requiring management at a comprehensive stroke center. Other patient populations that have been studied include critically ill patients being trans erred to a hospital with greater intensive care capacity. Patients trans erred or reasons that all outside these parameters have been not been studied; thus overall best practices must be in erred rom the existing literature. Challenges that are speci c to interhospital trans ers can be divided up into risks prior to trans er, during trans er, and a ter trans er (Table 12-2). Prevention o decompensation during travel requires specialized transport and personnel and will not be covered in this chapter.

■ RISKS PRIOR TO TRANSFER Prior to trans er, the risks and bene ts o the trans er should be considered. While patients clearly bene t rom appropriate trans er to specialty acilities in the case o stroke, trauma, and acute coronary syndrome requiring percutaneous angioplasty, the bene ts o transer in other cases are less clear. There ore, a care ul review should be done by both the sending and receiving physicians to ensure that the patient is appropriate or trans er and that the bene t o care received at the receiving acility will outweigh the risks o trans er. In the case o the patient requesting the trans er, a thorough conversation should occur to ensure that the patient (a) is not requesting the trans er merely because o poor communication at the sending acility and (b) is not overestimating the impact o quality metrics at the receiving acility. In the case o a patient who is perceived to require specialized care, the sending hospitalist, the sending subspecialist (i available), the receiving subspecialist, and the receiving hospitalist should con erence to determine medical necessity and plan o care, both to initiate care and ensure that appropriate care is immediately implemented upon the patient’s arrival. Except in cases o urgency, overnight trans ers should be avoided as these have been shown to have more negative outcomes. 82

Another risk inherent to interhospital trans ers is in delaying the appropriate care o the patient. Delays in patient care are multiactorial and can be caused by lack o expertise at the trans erring acility as well as delays in acceptance at an appropriate acility and arrangement o transportation. Minimizing these delays requires a coordinated ef ort among administrators, physicians, and medical staf . Trans er centers and rapid trans er protocols at large medical centers have helped acilitate trans ers by (a) ensuring that a bed is available at the appropriate level o care; (b) coordinating conversations between the sending and receiving physicians; and (c) in some cases, “triaging” trans ers to ensure that those with the most urgent needs have priority. Delays in care initiation can be minimized by the receiving physician making treatment recommendations to the sending physician when applicable. Implementation o the proposed therapy should be up to the discretion o the sending physician. In addition, coordinated ef orts can also determine optimal timing and method o transport. I trans er is delayed by more than a ew hours, a repeat verbal conversation should occur between the current sending and receiving physicians to ensure that no changes have occurred and that the physician who is receiving the patient at time o trans er has the opportunity to ask clari ying questions. I at any point a patient has a change o status, this should be communicated to the receiving physician as well.

■ RISKS AFTER TRANSFER Once the patient has trans erred, the main risks are with discontinuity o care plans—both discontinuity o care between the sending and receiving acilities and discontinuity once the patient has been discharged or sent back to the receiving acility. In addition, transerred patients o ten receive unnecessary repeat imaging or testing, leading to increased charges and radiation doses. To minimize discontinuity, best practice suggests the inclusion o the ollowing in the documentation sent to the receiving hospital: re erring physician and contact number, reason or trans er and nature o illness or injury, current and outpatient medications, vital signs and relevant physical ndings at time o trans er, results o pertinent diagnostic studies, treatment up until time o trans er, and pending tests (including cultures). Use o a standardized accept orm—either by the sending or receiving acility—have been shown to reduce missing in ormation. Another method to minimize discontinuity, particularly or patients being trans erred or a single procedure, is to trans er the patient back to the sending acility when appropriate. At time o discharge, care should be taken by the receiving acility to include the relevant hospital course and diagnostic ndings rom the sending hospital into the discharge in ormation sent to the patient’s outpatient physicians. Failure at any point reduces quality and delays intervention, leads to inappropriate allocation o resources, and increases the nancial burden on the patient, hospital, and health care system.

PRACTICE POINT

• •Intrahospital trans ers are at high risk or dropped patient in ormation and delays in patient care. Risks may be minimized by (a) creating guidelines to ensure that patients are being trans erred appropriately; (b) acilitating conversations between the sending and receiving physicians, in addition to any relevant subspecialists; (c) providing treatment recommendations to the sending physicians when appropriate; and (d) creating standardized checklists or documentation required upon trans er and upon discharge. Trans er centers and rapid trans er protocols can help streamline many o these processes.

Gri ths D, Morphet J, Innes K, Craw ord K, Williams A. Communication between residential aged care acilities and the emergency department: a review o the literature. Int J Nurs Stud. 2014;51:1517-1523.

C H A P T E R 1 2 C a r e T r a n s i t i o n s i n t o t h e H o s p i t a l : H e a l t h C a r e C e n t

Admissions from Skilled Nursing Facilities

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Iwashyna T. The incomplete in rastructure or interhospital patient trans er. Crit Care Med. 2012;40:2470-2478.

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Hernandez-Boussard T, Davies S, McDonald K, Wang N. Interhospital acility trans ers in the United States: a nationwide outcomes study. J Patient Saf. 2014 [epub]:Nov 13

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Van Blarcom JR, Srivastava R, Colling D, Maloney CG. The development and implementation o a direct admission system at a tertiary care hospital. Hosp Pediatr. 2014;4(2):69-77.

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Eichner JE, Cooley WC. Coordinating the Medical Home with Hospitalist Care. Hospital Pediatrics Online. 2012;2(2):105-108. Available at http://hosppeds.aapublications.org. Accessed May 18, 2015.

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Carrier E, Yee T, Holzwart RA. Coordination between Emergency and Primary Care Physicians. National Institute or Health Care Re orm Research Brie Number 3; February 2011.

e p t m e n t , O u t s i d e H o s p i t a l T r a n s e r

Beach C, Cheung D, Apker J, et al. Improving interunit transitions o care between emergency physicians and hospital medicine physicians: a conceptual approach. Acad Emerg Med. 2012;19:1188-1195.

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rom SNFs/SARs are at high risk o medication errors and unnecessary testing and treatment. Providing partnering SNFs/SARs with standardized trans er orms may help improve communication.

Admissions from the Ambulatory Health Care Center

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Snow V, Beck D, Budnitz T, et al. Transitions o Care Consensus Policy Statement American College o Physicians-Society o General Internal Medicine-Society o Hospital Medicine-American College o Emergency Physicians-Society o Academic Emergency Medicine. J Gen Intern Med. 2009;24(8):971-976.

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Singer A, Thode H, Viccellino P, Pines J. The association between length o emergency department boarding and mortality. Acad Emerg Med. 2011;18:1324-1329.

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While patients rom skilled nursing acilities (SNFs) or subacute rehabilitation acilities (SARs) usually present to the hospital through the ED, they nevertheless represent a signi cant care transitions challenge or the hospitalist. Not only are they usually medically complex, they also requently are unable to provide a coherent medical history or describe their medication regimen. In addition, they are less likely to be accompanied by a relative or caregiver than elderly patients who present rom their homes. In recent studies, up to 10% are trans erred to the ED without any documentation and up to an additional 40% are missing in ormation. Most requently absent rom the documentation are baseline cognitive unction, current medications, and advance directive status. Because this population requently presents with non-speci c complaints such as alls, dehydration, or con usion, these omissions resulted in more investigations, particularly head CTs. They are also at risk or medication errors, unnecessary testing, and inappropriate/unwanted care. While there have been ew studies looking at interventions, one study showed that while providing the SNFs/SARs with trans er orms did not result in a signi cant use o the trans er orms, ollow up ound that the data transmitted still improved. There ore, hospital medicine groups should strongly consider partnering with the SNFs/SARs that requently send patients to their acility. There is no consensus on in ormation that should be included on trans er orms, but recommendations include reason or ED trans er, past medical history, baseline cognitive unction, medication list and mediation allergies, vital signs at time o complaint, advanced directives, contact in ormation or the SNF/SAR’s health care provider, and contact in ormation or the patient’s next o kin or medical decision maker.

Horwitz L, Meredith T, Schuur J, Shah NR, Kulkarni RG, Jeng GY. Dropping the baton: a quality analysis o ailures during the transition rom emergency department to inpatient care. Ann Emerg Med. 2009;53(6):701-710.

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Care Transitions within the Hospital: The Hand-Off Vineet M. Arora, MD, MAPP Jeanne M. Farnan, MD, MHPE

INTRODUCTION In-hospital care has su ered as a result o the increased ragmentation in the delivery o care, speci cally secondary to new clinical models such as the rise o hospitalist care in the United States, and the move toward cutting hours or residency trainees in teaching hospitals. This ragmentation has resulted in a greater need or care coordination and a ocus on transitions, particularly or the hospitalized elderly population. For example, or a typical patient, a member o the patient’s primary team is present in the hospital only 50% o the time. Hospitalized patients are passed between doctors an average o 15 times during a single 5-day hospitalization. In addition to the ocus on end-o -shi t changes that are germane to hospital medicine, there is increasing recognition that the ocus on hando behaviors needs to extend to cover the vulnerable “service change,” which represents a more permanent change in primary hospital care provider. While the current literature has ocused on strategies or to e ectively “give” in ormation during the hando , recent literature has also highlighted the need to examine the critical role o the receiver. The hando is a uid, dynamic exchange that is subject to distraction, interruptions, uctuates on aptitude o and con dence in o -going and on-coming clinician and is contingent on the on-coming clinician’s con dence in the quality, completeness o the in ormation. Cook et al (2000) While the scope o Cook’s de nition re ers primarily to shi t change, the term handof s has taken on a li e o its own, with the term being used synonymously with a broader set o care transitions, such as admission, discharge, and even communication between outpatient physicians. In this chapter, we will ocus on the skills that are essentially to those hando s which permeate the in-hospital setting or hospitalists, with a special ocus on shi t and service change, as well as introduce assessment strategies to ensure the sa ety and ef cacy o these hando s. TYPES OF INTRAHOSPITAL HANDOFFS

■ SHIFT CHANGE Shi t change is the trans er o content and pro essional responsibility rom one clinician to another at the end o the shi t. One important distinction among shi t changes is whether the outgoing clinician is returning to assume ongoing care o this patient or the hando is just a temporary coverage or emergencies until the primary team returns. In the case o the latter, the covering physician is o ten accepting a hando only to manage overnight emergencies, but planning and execution o care are largely on hold. • • Signout: A type o shi t change that o ten pre erentially re ers to

a primary team who is assuming care o the patient and transers care temporarily to another clinician and that primary team member will return to assume care o patient. Can also re er to the written document used to trans er in ormation. It can also re er to the time period when people are actively handing over patients to another group o providers. • • Cross-coverage: The care that a clinician provides when “covering” a patient whose daily responsibility is assumed by another clinician or team. 84

In considering the various risks associated with these hando s, a white paper rom University Health System Consortium suggests that the ollowing three questions can be used to triage risk to patients during hando s: (1) Is the patient physically moving? (2) Is the hando permanent (more than just a ew hours or a night)? (3) Is the patient unstable? I the answer to any o these questions is a yes, then the risk is inherently higher. There ore, the highest risk transitions may be a service trans er to the ICU or emergent surgery—since the patient is unstable, moving, and it is a “permanent hando ,” meaning more than just a ew hours. Another example certainly includes the service change, in which the hando is permanent and the clinician is likely not returning to assume care o the patient. In addition to these questions to strati y risk during hando s, another philosophy that has emerged is the concept o “common ground”—or rather how much knowledge do the incoming and outgoing clinicians already share about the patient? When a receiver may not know a patient at all, the hando may be at greater risk due to the high degree o uncertainty that can cloud the initial evaluation o a patient. This is not only true during service and shi t hando s, but other trans ers o care, such as a patient being admitted rom the emergency department to the hospitalist on the oor. Uncertainty is a de nite risk or patients and has been demonstrated to lead to patient harm or near misses and inef cient work in both resident signouts and hospitalist service changes. In addition, uncertainty can also lead to rework, including procedures and testing, which may also negatively impact the patient’s overall care. There ore, hando s are inherently risky when the receiver does not have any a prior knowledge o the patient (Table 13-1). CORE COMPONENTS OF HANDOFFS Regardless o the type o in-hospital transition involved, hando s have the common goal o creating a shared mental model between the sender and the receiver in order to ensure that surrogate

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A hando typically, and ideally, has some element o verbal communication, either ace-to- ace or over the phone. The goal o verbal communication is o ten to build a shared mental model or a patient, with a ocus on anticipatory guidance and tasks to be done and the rationale which accompanies those tasks, as well as their priority. Verbal communication also allows or other critical actions such as questioning and reading back in ormation relayed and received. One key eature o verbal communication is that it should not “rehash” what is already available in printed or electronic records. It is important to strike the right balance between too much and too little in ormation, particularly to ocus on what the receiver really needs to know. While verbal ace-to- ace communication is not always possible, it is certainly the ideal as it provides or these opportunities. During shi t change in hospitals, this process is o ten called “signing out.” During an admission, this could take the orm o a report given over the phone between the emergency room physician and the hospital-based physician.

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■ VERBAL COMMUNICATION

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RISK STRATIFICATION OF HANDOFFS

decisions and judgments. Certain core elements o hando s include the ollowing:

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Service trans er is the change o service o a patient rom care o one group o clinicians to an entirely di erent group o clinicians, usually rom a di erent specialty or ward, to receive a di erent service that is unique to the receiver’s specialty or ward. This could include an “escalation o care” due to worsening patient illness (trans er to the intensive care unit) or trans er to a subspecialty service or a speci c management issue (trans er rom medicine team to surgical team or procedure and postoperative care). As with the service change, the service trans er is accompanied by a verbal exchange o patient in ormation as well as a comprehensive trans er summary which includes a written documentation o the patient’s reason or trans er and detailed in ormation about their hospital course.

(1) Is the patient physically moving? (2) Is the hando permanent (more than just a ew hours or a night)? (3) Is the patient unstable? (4) Is this the irst time the receiver is hearing about a patient?

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■ SERVICE TRANSFER

TABLE 13-1 Questions to Risk Stratify Handoffs—If Yes, to Any, Inherently Higher Risk

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A service change is a permanent trans er o content and pro essional responsibility at the end o one’s on-service time or rotation to a new physician or team o providers who will assume ongoing care o the patients. This service hando is o ten more extensive and includes description o the initial reason or the patient’s need or hospitalization, hospital course to date, current status, and anticipated plan o care, including discharge. The timing o the service change is driven by the duration o the rotation and can happen as requently as weekly to as long as monthly. Service changes may not always include ace-to- ace opportunities or discussion and are requently supplemented with a written account o the patients’ hospital course, o ten re erred to as an “o -service note.”

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■ SERVICE CHANGE

■ WRITTEN COMMUNICATION There is usually some orm o a written communication (or “transition record”) that supplements the verbal hando with additional in ormation that could become important at a moment’s notice, such as the patient’s primary care physician or code status. The written hando document generally either is a user-created document that is computer-based, is auto-generated by the electronic medical record (EMR), or is a hybrid o these. O ten, this written communication is used as a peripheral guide or the conversation during the verbal hando o in ormation. During shi t change in many academic teaching hospitals, this written communication is known as the signout.

■ TRANSFER OF PROFESSIONAL RESPONSIBILITY A hando is more than just the trans er o in ormation; it is also the trans er o pro essional responsibility. Acknowledgment o the accountability or a patient’s care is an important eature o success ul hando s. Given the need or requent shi t handover in the current hospital systems, this is a critically important step in the process. Prior work has indeed demonstrated that the being cared or by a crosscovering physician is associated with an increased risk o preventable adverse events. The etiology o this risk is multi actorial. Not only do covering physicians lack the primary knowledge regarding a patient they are caring or, but they could also lack o pro essional ownership o patients who they did not directly admit or care or a on a more routine basis. While improving the process o hando s can increase the knowledge a covering physician, e orts to improve pro essional responsibility are equally important. In essence, a high-per orming team culture that unctions such that “every patient is our patient” is what is needed to support the necessary pro essional responsibility. 85

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S top pa tie nt ca re ta s ks to conduct ha ndoff

S pe cific ve rba l excha nge be twe e n s e nde r a nd re ce ive r (could be in pe rs on or ove r phone )

Re ce ive r inte gra te s new informa tion a nd a s s ume s ca re of pa tie nt(s )

Pre -hando ff

Arrival

Dialo g ue

Po s t-hando ff

• La ck of time, poor time ma na ge me nt, fa tigue, or work preve nts upda ting • La ck of clinica l judgme nt to cons truct prope r ha ndoff • Va gue la ngua ge

• No s e t loca tion or time • Not a ble to conta ct s e nde r or re ce ive r • Compe ting obliga tions (work or pe rs ona l) • Ha ndoff not a priority ove r ta s ks

Se n d e r c o u ld • Provide dis orga nize d info • Us e va gue or uncle a r la ngua ge • Fa il to provide clinica l impre s s ion (wha t is wrong), a nticipa tory guida nce (if/the n), pla n (to do), & ra tiona le (why)

• Forge t key ta s ks or informa tion • Not docume nt a ctions ta ke n

Re c e ive r c o u ld • Not lis te n (dis tra ctions ) • Mis unde rs ta nd • Not cla rify (a s k que s tions )

• Act on pla n without ta king new a rriving informa tion into a ccount • Not inve s t in the ca re of pa tie nt (la ck of profe s s iona l re s pons ibility)

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S e nde r orga nize s & upda te s ha ndoff informa tion

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Figure 13 1 Phases o the hand-o .

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CORE STEPS TO THE HANDOFF PROCESS

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In addition to the core components o a hando , it is important to consider the core steps to the process o hando s. In thinking about hando s as a process, one can conceptualize our basic phases to the process. Modi ed rom a consensus paper or Emergency Medicine hando s, these our phases would include the ollowing (Figure 13-1): 1. Pre-handof : Sender organizes and updates written in ormation or hando . This o ten critical step will be discussed urther in hando ailures, as this is where many errors can occur. 2. Arrival: Sender completes patient care tasks to conduct hando (or participate in “signing out”). This step also includes the negotiation between sender and receiver or time and meeting place or the hando . 3. Dialogue: A speci c verbal exchange that takes place between sender(s) and receiver(s). This verbal exchange could either be ace-to- ace (o ten pre erred) or over the phone in cases when an in-person hando is not possible. 4. Post-handof : Receiver integrates new in ormation and assumes ongoing care o patient(s). DIFFERENTIAL DIAGNOSIS OF FAILED HANDOFFS Understanding the content and process o hando s is essential to understanding how hando s may ail. Each step in the process o hando s is prone to ailure as outlined here.

■ PRE-HANDOFF FAILURES Since the ocus o the pre-hando phase is to create and update the written communication or the hando , ailures in this phase lead to errors in the transition record. O ten the inability to carry out the pre-hando phase is due to lack o time, ine ective time management, workload, or orgetting to do so. Systems issues can contribute to the inability to update the written in ormation, including not scheduling protected time near the end o a shi t to ensure 86

in ormation trans erred is up-to-date, or more cultural issues such as a lack o priority or the signout process itsel . Failing to update the written communication can result in either omissions (in ormation not present) or commissions (in ormation provided is incorrect). For example, in one study o written signouts, 80% contained at least one medication omission and 40% one commission. Over hal had the potential to cause signi cant harm to a patient. Although omissions were more common, commissions, such as including medications that were not actively being used in the patient’s care, were more serious. Examples included anticoagulants, intravenous (IV) antibiotics, narcotics, and hypoglycemics (insulin, etc). While the advent o EMR, and the ability to auto ll certain elds, including medications, has helped to minimize the medication omission and commission errors, prior data has established that technological solutions alone are not robust enough to prevent hando related errors such as these. For these reasons, written communication that is linked to the electronic health record is o ten pre erred although care must be taken to ensure the written section is updated daily as well. In addition to omissions and commissions in the written communication, the use o vague language such as “today,” “tomorrow,” or “yesterday” can result in con usion as can the use o nonstandard abbreviations that either are not understood or can be mistaken or something else (eg, HL or hyperlipidemia, which is o ten perceived as Hodgkin lymphoma). Written communication can be plagued by the TMI (too much in ormation) phenomenon, in which extraneous and nonessential in ormation are included in the written signout which do not provide in ormation use ul or those covering the patient during a shi t hando and can serve to clutter the existing, use ul in ormation. Finally, cutting and pasting in ormation into the written signout document can also serve to perpetuate inaccurate in ormation.

■ ARRIVAL FAILURES Arrival ailures include not arranging a speci c location or time to meet or a hando . Even with a telephone hando , i a time is

■ DIALOGUE FAILURES Similar to arrival, the dialogue phase o hando s could result in ailure on the part o either the sender or the receiver. For example, the sender could provide disorganized in ormation; use vague or unclear language; or ail to provide enough clinical background to enable uture decision making. On the other hand, receivers could ail to listen due to either inattention or external distractions. They could also misunderstand the in ormation or ail to clari y any items they misunderstood through the use o questions. Both senders and receivers have a responsibility to ocus on the process, and are both critical actors in the trans er o in ormation. Data rom routine studies o human communication suggest that senders o ten overestimate how well receivers will understand the in ormation that they are trans erring. Interestingly, this worsens the more amiliar two people are with one another. This “egocentric heuristic” can lead to communication errors due to the use o vague language. For example, a husband may tell a wi e, “Meet me there a ter work” but not clari y where “there” is or whether he means a ter her workday ends or a ter his workday ends. In his mind, he understood what he was trying to say, but he did not e ectively communicate it. This same problem applies in hando s. A study o pediatric hando s in optimal conditions (dedicated room, time, limited interruptions) demonstrates that 60% o the time, the most important piece o in ormation about a patient was not communicated despite the sender believing it had been. In addition, the rationale or to-do actions was o ten not provided. A common example reported was that the covering intern was told to “check the CBC (complete blood count)” but not given any reason or doing so or what to do with abnormal results. This study occurred with optimal physical conditions and a dedicated time or the hando process, and still communication ailures and

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Post-hando ailures can take many orms, and one o the most common is the diminished pro essional responsibility toward patients o receivers who are “just covering the patient.” One key question is, “does the incoming clinician have the same investment in the patient care as the outgoing clinician?” It is o ten very clear when this is not the case. For example, night moonlighters or nocturnists may adopt an attitude that the patients they are caring or are “not their patients” and that their job is just to hold down the ort until the day team arrives. In these instances, the de ault could be to do as little workup as possible or any acute patient issues and de er to the primary team. While in many cases this “temporizing approach” may not result in any harm to a patient, there are clearly time when delays in clinical decisions could harm the patient. For example, a patient who is meeting sepsis criteria may not receive antibiotics because the night physician could be de erring the choice to the primary hospitalist. Likewise, in service changes, it is also possible that the physician who is leaving the service may no longer be invested in the ongoing care o the patient or patients, especially those who have been passed rom physician to physician in multiple service changes. Post-hando ailures in service trans ers could mani est in the receiving service never “learning the patient” or expediting discharge or a patient without ully addressing their issues because o a relative lack o pro essional responsibility.

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■ POST-HANDOFF FAILURES

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over-estimation o e ectiveness occurred. One way to mitigate the trap o the egocentric heuristic is to improve the “common ground” or the a priori knowledge that senders and receivers have about the patient. For example, i the night hospitalist has covered the patient be ore, they have some “common ground” with the day hospitalist in the sense that they both have had some knowledge and interaction with the patient rom which the verbal hando can build. Improving common ground is a design problem—a key question is can you enhance the structure o the team or the schedule such that the receiver shares more a priori knowledge with the sender? In addition to ailures on the part o senders and receivers, in ormation transmission can be hampered due to noisy, distracting settings that discourage conversation, the hierarchal nature o medicine (which can discourage open discussion between providers), language barriers, lack o ace-to- ace communication, and time pressures that lead to a hurried dialogue. Using this ramework, service trans ers could be especially prone to communication ailures due to dialogue ailures i the services are rom di erent disciplines (eg, emergency medicine and hospital medicine) since the sender and receiver may have very di erent expectations o the level o detail or type o content to be reviewed. In this setting, the lack o a “shared mental model” or the hando is missing, and there ore it is likely that the hando may be unsatis actory to one or both parties.

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not speci ed, the sender or receiver may ail to make contact at the hando time. Moreover, experienced hospitalists may make an assumption that they do not “need” a verbal hando , since their experience will be enough to guide them on what to do. It is equally possible that the high workloads night hospitalists ace may hinder verbal hando s, because the night hospitalist is covering too many patients or a meaning ul verbal hando to occur. Likewise, other work demands (competing clinical work, unstable patient, etc) or personal issues (late to work or having to leave work early due to amily illness) can also compromise the arrival phase o a hando . Systems issues can also contribute to arrival ailure, with shi ts that start and end at the same time, requiring either one individual stay late or one arrive early, in order to provide adequate time to e ectively transition patients. This is especially likely i the hando does not take explicit priority over other clinical tasks. For example, the sender could be ready to arrive to the hando but the receiver could be in the operating room. For service changes, this is especially problematic as residents and aculty are o ten transitioning rom other rotations, such as vacations or elective time, and so may not be physically present in the same city, or have access to the EHR or even e-mail. Identi ying a time to turn over a service also requires that the individual handing o is aware o the identity o their replacement, and in some systems this can pose a challenge. When the trans er o content is separated in time and space rom the trans er o pro essional responsibility, arrival ailures can o ten arise. For example, during service trans ers, such as rom the ICU to the oor, it is possible that due to timing o bed availability a di erent team may receive the patient than originally received the transer hando . This is o ten exacerbated during times o bed shortages, since days may elapse rom when a trans er is initiated to when a patient actually receives a bed.

STRATEGIES FOR IMPROVEMENT In the e ort to improve in-hospital hando s, The Joint Commission made standardized hando communications the subject o a 2006 national patient sa ety goal requiring institutions to “implement a standardized approach to hando communication, including an opportunity to ask and respond to questions.” Critical elements in this standardized model should include an interactive, timely process that contains up-to-date in ormation with minimal interruptions. Evidence or these goals emerges rom the experience o other industries, trials o technological solutions, or communication practices in health care. 87

■ STANDARDIZED OR STRUCTURED TEMPLATES FOR WRITTEN HANDOFF INFORMATION

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The importance o the implementation o a standardized strategy is critical or both the verbal and the written component o the intrahospital hando . The use o standardized language during the verbal hando helps to ensure transmission o consistent in ormation and allows or interactivity in the hando . One popular model is the Situation Brie ng model (SBAR), which is a technique that originated in the U.S. Navy to ensure the relay o critical in ormation. SBAR has been used success ully by allied health pro essionals, such as in nursing. Other mnemonics that have been used include SIGNOUT?, ANTICipate, HANDOFF, and IPASS. A prior systematic review o hando mnemonics yielded 46 articles detailing 24 hando mnemonics; ew were evaluated or validated in research settings. Several institutions have success ully used structured templates, such as computer-aided and electronic health record (EHR)-aided signouts, to ensure the transmission o accurate and updated in ormation in the written component o the hando . In act, Petersen and colleagues demonstrated a trend toward reduction o preventable adverse events a ter the implementation o a computerized signout system over 20 years ago! Lee and colleagues demonstrated in a randomized, controlled trial that a standard signout guide that ensured the inclusion o critical content resulted in improved written signout quality. However, using a standardized template or communication does not mean it is updated and has the correct or most pertinent in ormation or the covering physician. Not only is it critical to ensure that the in ormation included in the written signout is accurate, it is equally important to ensure adequate time to per orm this update. Technological solutions, when combined with systems changes, can yield the best results.

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■ FACE-TO-FACE VERBAL UPDATE WITH

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INTERACTIVE QUESTIONING Studies o shi t Changes in other industries highlight that the use o ace-to- ace (in person) verbal update with interactive questioning is critical in conducting an e ective hando . Studies o health care pro essionals demonstrate general agreement with this principle. Moreover, ace-to- ace verbal update is o ten suggested as a recommendation or inpatient hando s.

PRACTICE POINT

• •Major strategies to improve intrahospital hando

s include standardized or structured templates, ace-to- ace verbal update with interactive questioning, an emphasis on anticipatory guidance and tasks to be done, and use o read-back.

■ EMPHASIZE ANTICIPATORY GUIDANCE AND TASKS TO BE DONE Receivers o intrahospital hando s o ten state that they need only the pertinent in ormation—what may happen and what to do about it. Un ortunately, the actual practice is o ten that the sender provides too much in ormation or too little in ormation. As a result, emphasis on these items can be especially help ul to hone receiver understanding o the patient. Indeed, one study shows that a ter the receipt o an intrahospital hando , receivers are more likely to remember “i /then” items or “to-do” items more than general knowledge items about a patient. Moreover, the Society o Hospital Medicine Hando s Task Force recommends that “insight on what to anticipate and what to do is the ocus o the verbal exchange” and 88

that “anticipated events are clearly labeled” and “tasks to be done are highlighted” or incoming hospitalists. Avoiding editorializing and extraneous in ormation allows the hando to be a streamlined ow o clinically use ul in ormation that is pertinent or the covering (receiving) physician and allows the sender to create a picture or their shared mental model.

■ USE OF READ-BACK Read-back allows the physician receiving the hando to check the in ormation received rom the sender. The use o read-back is also a Joint Commission requirement or receipt o critical lab tests. Use o read-back has been shown to reduce the number o laboratory reporting errors during requested read-back o lab results. Although per orming a read-back o the entire verbal hando could be cumbersome and undesirable, the use o ocused read-back can enhance memory or the high-priority items o a verbal hando , namely tasks to do, and to clari y anticipatory guidance as already highlighted. One misconception about read-back is that it does not need to occur or every patient on the hando , but can occur as a part o a synthesis or a ‘chunk’ o patients, or or an entire hando .

■ IMPROVING PROFESSIONAL RESPONSIBILITY DURING HANDOFFS While it is hard to imagine telling people to be more “pro essional” during hando s, it is worth noting that some organizational cultures and systems do a better job o promoting this shared responsibility, or what has been described as “continuity-enhanced” hando s. For example, systems in which the sender and receiver both meet the patient rst hand since they unction on the same team are likely more e ective at promoting common ground and pro essional responsibility than a system in which the receiver is a “hired gun” that is “just covering.” While this type o system is not technically easible or essential or all patients, it may be bene cial or the sickest patients, such as those that are in an ICU setting, who depend on a high degree o primary knowledge regarding their hospital course. Another model or improving pro essional responsibility during the post-hando period that alls short o having the sender and receiver both “know the patient” is to ensure a structure o repeated interaction between the sender and receiver such that trust is built between both parties. This could be accomplished in multiple ways, including a system that schedules hospitalists or blocks and avoids having a new clinician each night or day. This could improve pro essional responsibility or a good hando and post-hando care since both the sender and receiver will ace each other again in the uture and have an opportunity to receive ollow-up or updates on any clinical questions that were outstanding at the time o the initial hando . EDUCATION, EVALUATION, AND SIMULATION Given recent regulatory, accreditation and education requirements, several educational curricula geared toward teaching trainees and aculty e ective hando strategies have been piloted and evaluated. In act, educators have encouraged raming the approach to hando education as one would any other entrustable pro essional activity, in a milestone-directed ashion tied to the measurement o competency. One large multisite study in pediatric teaching hospitals tested the e ectiveness o the IPASS initiative, a hando improvement “bundle” which includes a mnemonic to standardize oral and written hando s, hando communication training, patient sa ety culture training, and aculty development in hando observation and a sustainability campaign. The evaluation o this educational bundle was shown to decrease the rate o preventable adverse events in the postintervention period, as well as signi cant reduction in error rates and a signi cant increase in the quality o

CONCLUSION Ensuring sa e and e ective hando s is critical to patient sa ety and the delivery o quality care. These hando s occur during times o patient care transition in the hospital setting. To ensure the

Riesenberg LA, Leitzsch J, Little BW. Systematic review o hando mnemonics literature. Am J Med Qual. 2009;24(3):196-204. Starmer AJ, Spector ND, Srivastava R, et al. Changes in medical errors a ter implementation o a hando program. N Engl J Med. 2014;371:1803-1812.

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Hinami K, Farnan JM, Meltzer DO, et al. Understanding communication during hospitalist service changes: a mixed methods study. J Hosp Med. 2009;4(9):535-540.

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Greenstein EA, Arora VM, Staisiunas PG, Banerjee SS, Farnan JM. Characterising physician listening behaviour during hospitalist hando s using the HEAR checklist. BMJ Qual Sa . 2013;22(3):203-209.

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Cheung DS, Kelly JJ, Beach C, et al. Improving hando s in the emergency department. Ann Emerg Med. 2010;55(2):171-180.

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Chang VY, Arora VM, Lev-Ari S, D’Arcy M, Keysar B. Interns overestimate the e ectiveness o their hand-o communication. Pediatrics. 2010;125:491-496.

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Arora VM, Manjarrez E, Dressler DD, et al. Hospitalist hando s: a systematic review and task orce recommendations. J Hosp Med. 2009;4(7):433-440.

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Arora VM, Berhie S, Horwitz LI, Saatho M, Staisiunas P, Farnan JM. Using standardized videos to validate a measure o hando quality: the hando mini-clinical examination exercise. J Hosp Med. 2014; 9(7):441-446.

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continued provision o sa e care during these transitions, providers should be aware o the types o transitions and the ways in which these transitions represent vulnerability or patients and their sa ety. With this knowledge, employing strategies to ensure e ective communication is critical to the delivery o sa e patient care during transitions.

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hando s. While this curriculum holds great promise, understanding what parts o the bundle worked most e ectively as well as why it did not work in all sites is important. Several other curricular bundles exist within the literature, based upon specialty ocus area and program need. In addition, longitudinal approach to hando education, beginning in medical school, predicts improved per ormance on standardized measures, and com ort with hando s as an early trainee. However, the education needed is not just at the student or resident level. Faculty-based education is required in order to ensure the ef cacy and quality o observed trainee hando s. Work done at the University o Chicago has demonstrated that the use o video-based scenarios in a aculty development program led to valid reliable rating instrument, the mini Hando CEX. While several validated instruments exist or measuring in vivo hando behaviors, the development o standardized, objectives clinical encounters (OSCEs) to measure hando quality, are only beginning to be recognized as a method o evaluation. Prior work has demonstrated that a simulation-based exercise or students, in which a mock, or standardized hando was per ormed, improved con dence and sel -ef cacy when per ormed at the transitional time period in the ourth year. Finally, although most educational and evaluation modules ocus on the communication skills o the sender, we are just now realizing the need or training on how to be an e ective receiver. As we have discussed, hando s are o ten plagued by interruptions, both clinical and otherwise, as well as reluctance to question colleagues, and competing demands on our attention. Work done within hospital medicine has demonstrated that the longer the hando , and the more patients signed over, the higher the likelihood o interruption. In addition, this work has generated the HEAR checklist, an observation-based instrument which allows or the evaluation o the receivers listening behaviors.

UHC Best Practice Recommendation: Patient Hand O Communication White Paper. University Health System Consortium; May 2006.

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14

CHAP TER

Care Transitions at Hospital Discharge Kelly Cunningham Sponsler, MD, SFHM

INTRODUCTION Hospital discharge is a critically important care transition. Due to the complexity and potential or errors inherent in the discharge process, this care transition continues to be an area o ocus or many patient sa ety organizations, regulatory agencies, and quality improvement initiatives. The discharge transition represents a vulnerable time or patients or several reasons. There is a shi t o responsibility rom the inpatient care team to the outpatient or postacute care providers, and with that comes great risk or breakdown in communication. Medications and other treatment plans are o ten adjusted in the hospital, and patients and caregivers are challenged with new sel -care tasks and ollow-up responsibilities at hospital discharge. Adverse outcomes are common in the postdischarge period, with studies showing that about one-hal o patients experience a medical error and approximately one in ve patients su er an adverse event. These adverse events, which include adverse drug events and increased health care utilization such as unscheduled hospital readmissions and emergency department visits, are o ten judged to have been preventable. Table 14-1 outlines some o the patient, clinician, and system actors that contribute to unsuccess ul discharge transitions. RISK STRATIFICATION Due to the complexity o care transitions, all patients are potentially at risk or an unsuccess ul hospital discharge. However, certain patient populations may be at higher risk than others. Most studies o discharge interventions have targeted geriatric patients or patients with speci c disease processes, such as congestive heart ailure, as these populations are known to have high rates o hospital readmission, upward o 20% within 30 days. Other patient-speci c characteristics, such as low health literacy, low socioeconomic status, and psychiatric comorbidity are also associated with worse outcomes a ter discharge. While it is important to have standardized care processes in place that acilitate sa e transitions or all types o patients, it is advantageous to have strategies or identi ying patients who may bene t rom more intensive care transitions interventions. There have been several tools and models developed to identi y patients who are at highest risk or readmission. However, these models are not able to ully and reliably predict hospital readmission, and many incorporate administrative data that can be burdensome to collect. Thus, having a process to easily ag patients with certain high-risk disease processes, psychosocial actors, and/or requent health care utilization, is optimal. A ew o the more commonly used scoring systems are listed in Table 14-2. The LACE index incorporates hospital length o stay, acuity o the admission, comorbidity measured with the Charlson score, and emergency department visits in the previous 6 months to predict the rate o readmission or death within 30 days. The 8P risk scale, part o Project BOOST (Better Outcomes by Optimizing Sa e Transitions), accounts or prior hospitalizations, problem medications, psychiatric problems, principal diagnosis, polypharmacy, poor health literacy, patient support, and unmet palliative needs. The HOSPITAL score was more recently published and was designed to predict potentially avoidable readmissions. Variables include discharge hemoglobin 1 h per day, 5 d per week; initial physician visit required within 30 d o admission to acility

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Skilled nursing facilities (SNF)

Multimodal services, at least 3 h per day

Lab and radiology available, some ability to handle unstable patients

Daily or near-daily Multimodal physician visits; services consultant specialists widely available

Lab and radiology available, some ability to handle unstable patients

30 minutes o critical care is provided by the consultant, only critical care [99291, 99292] and no other consult code set would be reported or that day. In the event that a consult is completed and at a later time on that calendar date, the consultant provides >30 minutes o critical care to the patient, both the consult and critical care service can be paid. The consult work would be reported using the rules above to select the appropriate code set.

■ SPLIT/SHARED VISITS Although previous guidance rom Medicare has stated that a consult cannot be provided as a split/shared service, those rules only

TIME-BASED BILLING Several E/M services can be billed based on time (Table 28-1), with di erent billing nuances or each code set. In certain situations, the rules allowing reimbursement or these services di er between the CPT and Medicare manuals. When billing based on time, the only time that can be counted toward reimbursement o a service, is

C H A P T E R 2 8 C o n s u l t a t i o n , C o m a n a g e m e n t , T i m e B a s e d , a n d P a l l i a t i v e C a r e B i l

When counseling and/or coordinating care (CCC) is the dominant eature o certain E/M visits, that is, when more than 50% o the total visit time ( ace to ace and/or unit/f oor), is spent counseling the patient and or coordinating their care, the level o service provided may be determined by the total visit time rather than by quanti cation o the documented history, physical, and medical decision making (MDM). The typical total visit times associated with these services are shown below. For example, i a patient is seen or inpatient ollow up o a pulmonary embolism (PE) and a compliant level 2 [99232] visit is documented based on history, physical, and MDM, but it is also documented that >50% o a 35-minute ace-to- ace visit is spent counseling the patient on risk actors or a PE, evaluation, and treatment, time is now the controlling actor and a level 3 [99233] visit can be billed even though the history, physical, and MDM only amount to a level 2. Medicare will only allow time-based billing or CCC or inpatient admissions and ollow-ups [99221-99233], SNF admissions and ollow-ups [99304-99318], new outpatient visits [99201-99205], established outpatient visits [99212-99215], and other home services [99324-99350]. Medicaid and other insurers who ollow the CPT handbook may also allow time-based billing or CCC or observation services [99218-99236] and consults [99241-99255] as well. The Medicare Claims Processing Manual Chapter 12 states that the amount o CCC time may be estimated. In addition, the CPT manual instructs the provider to round the total visit time to the closest “average” total visit time. Thus in the example above, i 32 minutes were spent with the patient, 32 is closer to 35 minutes (average visit time or a level 3 ollow-up [99233]) than it is to 25 minutes (average visit time or a level 2 ollow-up [ 99232]), and a level 3 service would be billed. This di ers rom the rules governing prolonged service total time determination below. Tasks that count toward counseling the patient include but are not limited to discussions o the plan, evaluation, procedures, prognosis, treatment options, risk actor reduction, and patient and amily education. In order to bill or these services, two dif erent amounts o time must be documented: the total visit time, and the portion o that total visit time that was spent CCC. Check with insurers and local compliance o ces to see i the term “>50% o the total visit time was spent counseling the patient” is acceptable or i the speci c number o minutes spent CCC needs to be explicitly documented. Neither the Medicare manual nor the CPT handbook list this as a documentation requirement. The most common documentation pit all in success ully getting reimbursed or CCC time, is reporting only one time amount, thus making it impossible to determine that >50% o the total visit time was spent CCC. In addition, lack o a brie description o what was discussed during that time will cause a denial; the medical necessity or investing that time into the visit may not be obvious.

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■ COUNSELING AND COORDINATION OF CARE

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The terms “comanagement” and “concurrent care” are o ten used interchangeably. Concurrent care is the situation when two physicians are managing di erent aspects o the patient’s care on the same calendar date on a more extensive basis than a one-time consultation, usually discussed in re erence to two physicians submitting claims or inpatient ollow-up services [99231-99233]. Two initial inpatient services [99221-99223] submitted on the same calendar date will be interpreted as consultation care and not all under this discussion. The Medicare manual clearly states that the work o both physicians is reimbursable as long as the documentation ref ects the medical necessity or each physician to provide their service. Although the two physicians are usually rom di erent subspecialties, in the event that both are rom the same specialty but one has documented expertise above and beyond the other, both services may be paid. An example o this could be an internal medicine hospitalist who is managing a patient with a COPD exacerbation, but elicits the help o another internal medicine hospitalist with expertise in pain management, to take over the daily care o the patient’s severe re ractory chest pain rom lung cancer. The medical necessity o each physician’s care should not only be ref ected in the medical record, but also by each claim being submitted with di erent ICD-10 codes, showing the di erent aspects o care each provider is managing on that particular date. I both providers submit their service with the same primary ICD-10 code, only the rst claim received by Medicare will be reimbursed. The second one will be denied. Comanagement, de ned by the Society o Hospital Medicine (SHM) and its Advisory Panel, is the “shared responsibility, authority, and accountability or the care o a hospitalized patient.” By convention, this term is used when a more ormal arrangement is made between two physicians providing concurrent care. In the common situation involving a surgeon and medicine provider, the surgeon manages surgery related issues and the medicine hospitalist manages the patient’s medical conditions on an ongoing basis, o ten or the entire duration o the admission, and usually with the ormal arrangement outlining each specialty’s responsibilities. From the start, the patient will be admitted to one service, with an order or the other subspecialty physician to see the patient. Just as in the example in the consult section above, the documentation must support the medical necessity or the second physician to be involved, not just or the initial visit, but also or each daily visit. Situations will arise where each physician in a comanagement arrangement may not need to see the patient every single day o the admission. No billing should be submitted or these days, even i the patient is physically seen by the physician, based on a mandated hospital protocol. Without documented medical necessity, this work is not reimbursable.

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the billing provider’s time, not time spent on patient care by the resident, student, social worker, or nursing sta . For hospital based services, in addition to ace-to- ace time, the majority o E/M services also allow inclusion o time spent by the provider on the patient’s f oor or in their unit (“unit/f oor time”) providing patient care, toward billable time. In general, time is added up rom 12:01 a m to 11:59 pm, not over a 24-hour period, and does not need to be continuous. One exception to this is in the event that a time-based service is started be ore midnight, continuously provided, but not completed until a ter midnight. The CPT handbook advises i this should occur, to add up time that the service was provided continuously, and to bill or it on the date the service began.

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applied to consults reported with CPT codes 99241-99255. With Medicare consults now reported using di erent code sets, the rules or split/shared visits or Medicare patients now de ault to the rules or whichever set o codes are being reported or the consult. Thus, or inpatient consults reported with initial inpatient visit codes [99221-99223], these services can be provided and billed as split/ shared visits. Check with individual nonmedicare payors or their rules regarding this situation.

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TABLE 28-1 Average Visit Times or E/M Services Billed as Counseling/Coordination Services and Threshold Times or Prolonged Services

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Medicare allows billing or counseling/coordination time and prolonged service only or services in bold below. The CPTmanual allows both or all services in the table. Threshold to (Minutes) Average Threshold to CPT Code Visit Type Level Visit Time Bill 99356 Bill 99357 99218 105 Initial observation (1) 30 60 99219 (2) 50 80 125 99220 (3) 70 100 145 99221 Initial inpatient (1) 30 60 105 99222 (2) 50 80 125 99223 (3) 70 100 145 99224 Observation (1) 15 45 90 ollow-up 99225 (2) 25 55 100 99226 (3) 35 65 110 99231 Inpatient (1) 15 45 90 ollow-up 99232 (2) 25 55 100 99233 (3) 35 65 110 99234 Observation same (1) 40 70 115 day discharge 99235 (2) 50 80 125 99236 (3) 55 85 130 99251 Inpatient consult (1) 20 50 95 99252 (2) 40 70 115 99253 (3) 55 85 130 99254 (4) 80 110 155 99255 (5) 110 140 185 99304 Initial SNF (1) 25 55 100 110 99305 (2) 35 65 99306 (3) 45 75 120 99307 SNF ollow-up (1) 10 40 85 99308 (2) 15 45 90 99309 (3) 25 55 100 99310 (4) 35 65 110 99318 Annual NF 30 60 105 assessment (Minutes) Threshold to Threshold to CPT Code Visit Type Level Average Visit Time Bill 99354 Bill 99355 99201 New outpatient (1) 10 40 85 99202 (2) 20 50 95 99203 (3) 30 60 105 99204 (4) 45 75 120 99205 (5) 60 90 135 99212 Established (2) 10 40 85 outpatient 99213 (3) 15 45 90 99214 (4) 25 55 100 99215 (5) 40 70 115 99241 Outpatient consult (1) 10 40 85 99242 (2) 20 50 95 99243 (3) 30 60 105 99244 (4) 45 75 120 99245 (5) 60 90 135 CPT codes 99324-99350 not included in the chart above as not used in hospital medicine.

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■ PROLONGED SERVICES Prolonged service codes [99354-99359] are add on codes used when more than 30 minutes o care is provided beyond the typical or average visit time or the E/M service. They can never be billed alone, without their companion code—the primary E/M service. Time can be added up over the course o the calendar date not only by the provider, but also by their covering partners, including involvement by a nocturnist; the time each provider spent over the calendar date can be aggregated to determine to level o service provided. In this situation, the prolonged service would be reported under the NPI o the provider who is billing or the primary E/M service. Relative value units (RVUs) between the two providers would need to be adjusted internally or productivity purposes. Both physicians and nonphysician providers (NPPs) can bill or prolonged services. Finally, prolonged services may be provided and billed or as a split/shared visit. No restrictions are identi ed in either the CPT or Medicare manuals on how much time the physician must spend on the service relative to the NPP, in order to bill a split/shared visit. The documentation must clearly ref ect that each provider per ormed a substantive portion o the service.

C H A P T E R 2 8 C o n s u l t a t i o n , C o m a n a g e m e n t , T i m e B a s e d , a n d P a l l i a t i v e C a r e B i l l

1. I spent 25 minutes counseling the patient on new diagnosis o lung cancer. 2. I spent 15 minutes ace to ace with the patient discussing the hospital course or his pneumonia. 3. I spent 10 minutes out o a 30-minute visit counseling the patient on what CHF is, low salt diet, and decreased f uid intake (10 minutes is less than 50% o the total visit time). This visit cannot be billed based on time; the documentation o history, physical, and MDM would be used to determine the level o service. Speci cally, even though 10 minutes is >50% o a level 1 inpatient ollow-up average visit time (15 minutes), this statement cannot be used in lieu o documenting the history, physical, and MDM to bill or the service. 4. I spent today’s entire visit counseling the patient on the di erential diagnosis o his diarrhea and the planned work-up. (An auditor cannot try to determine how much time you spent with the patient based on the time orders were written, or the note was entered in the EMR. This service cannot be billed based on time.)

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Examples o unacceptable reporting o CCC time or billing:

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1. I spent 20 minutes out o a 25-minute visit ace-to- ace and unit/f oor time, counseling the patient on the sa e use o home oxygen, and coordinating care with social work, setting up home oxygen, home nursing, and pulmonary rehab (level 2 inpatient ollow-up visit [99232]). 2. I spent 35 minutes ace to ace with the patient today. Twentyve o those minutes were spent counseling the patient on her new diagnosis o breast cancer, the next steps in work-up, and possible treatment options including chemotherapy and XRT (level 3 inpatient ollow-up visit [99233]). 3. I spent 75 minutes with Mr X ace-to- ace and unit/f oor time. More than ty percent o that time was spent counseling the patient. The patient has very low health literacy and needed extensive counseling regarding acute renal ailure, necessary inpatient work-up, and possible need or dialysis (level 3 inpatient admission [99223]). 4. I spent 40 minutes ace to ace with the patient. One hundred percent o the time was spent counseling the patient on hospice and the grave prognosis or his metastatic lung cancer (level 3 inpatient ollow-up visit [99233]).

There are several di erences between Medicare and CPT manuals’ rules governing how and when prolonged services may be provided and how they must be documented. Medicare only allows prolonged services to be billed when the primary E/M visit is an inpatient admission or ollow-up [99221-99233], SNF admission or ollow-up [99304-99318], new outpatient visit [99201-99205], established outpatient visit [99212-99215], or home or domiciliary visit [99324-99350]. Medicare does not allow prolonged services to be billed with observation admissions and ollow-ups [99218-99236], however, the CPT manual does allow prolonged service billing with these observation services as well as with the consults codes [99241-99255]. For all payors including Medicare, prolonged services can never be billed with discharge management services [9923899239, 99217], critical care [99291-99292], or procedures. In general, the direct patient contact services 99356-99357 are added on to inpatient and observation services, and 99354-99355 are added on to outpatient services (Table 28-1). 99358-99359 are prolonged services without direct patient contact, that is, without a ace to ace, and are not reimbursed by Medicare. These codes are usually used when extensive time is spent in chart review. Payment or these services varies among private insurers. 99354, 99356, and 99358 are billed or the “ rst hour” o prolonged service provided. These services can be billed once 30 minutes o prolonged service has been provided; the rules governing prolonged service care allow or each unit o service to be billed once 50% o the service time in the description has been met. 99355, 99357, and 99359 are billed or each additional “hal hour” o prolonged service a ter the rst hour o prolonged care. These services cannot be billed unless 99354, 99356, or 99358 has already been billed with the primary E/M. Again, once hal o the time in the description is met, that is, 15 minutes, these services can be billed. Thus, in the inpatient setting, i 105 minutes o prolonged service has been provided beyond the typical visit time or the primary E/M visit, the rst hour o prolonged care may be billed, PLUS the next hal hour o care, PLUS another hal hour o care. In addition to the primary E/M service, 99356 and 99357 × 2 would be submitted in this example. No modi ers are needed or billing these services. Medicare requires the service to “meet or exceed” the threshold time to allow reimbursement or prolonged services (Table 28-1). Note that this is di erent rom the instruction to “round” to the nearest average visit time when billing or CCC. Thus i a level 2 inpatient visit is per ormed (typical visit time 25 minutes) and 52 minutes o ace-to- ace care was provided, the 55-minute threshold needed to bill or the rst hour o prolonged service [99356] has not been met, and the additional 27 minutes o care provided in this example is not reimbursable; only the level 2 inpatient ollow-up [99232] would be submitted or this care. Table 28-2 shows the cut o times needed to bill each unit o prolonged service. The rest o the discussion will ocus only on services with direct patient contact [99354-99357]. Medicare only allows ace-to- ace time with the patient to be counted toward prolonged service billing, both in the outpatient as well as the inpatient setting [99354-99357]. Notice that this is di erent rom Medicare’s rules or CCC, discharge management services, and critical care which all allow unit/f oor time to be included as well. The CPT manual de nes “direct patient contact” to mean only ace-to- ace time in the outpatient setting [99354-99355] but also time spent on the patient’s f oor or in their unit or inpatient services [99356-99357]. This has a large impact on how prolonged services may be billed. Prolonged services may be provided in addition to any level o service within the code sets above as long as >50% o the prolonged service time was not spent counseling the patient or coordinating their care. In the situation where CCC is the key eature o the visit, the highest level o service in the E/M code set must be used as the primary E/M be ore determining i any prolonged service time is

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Examples o minimally acceptable reporting o time or billing the visit based on CCC:

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TABLE 28-2 Prolonged Service Billing

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Minutes of Prolonged Service 0-29 30-74 75-104 105-134 135-164 165-194 195+

CPT Codes Submitted Outpatient Inpatient and Observation No Direct Patient Care Only primary E/M Only primary E/M Only primary E/M 99354 99356 99358 99354 + 99355 99356 + 99357 99358 + 99359 99354 + 99355 × 2 99356 + 99357 × 2 99358 + 99359 × 2 99354 + 99355 × 3 99356 + 99357 × 3 99358 + 99359 × 3 99354 + 99355 × 4 99356 + 99357 × 4 99358 + 99359 × 4 - - - - - - - - - - - - - - - - - - - ollow the pattern above - - - - - - - - - - - - - - - - - - -

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billable. I less than 30 minutes o prolonged services are provided, that work is not separately reimbursable. Example 1: A patient is seen with a new diagnosis o colon cancer and a ully compliant level 2 inpatient ollow-up visit [99232] is documented, based on history, physical, and MDM. Seventy- ve minutes o ace-to- ace plus unit/f oor time care (total visit time) is provided to the patient. Only 60 minutes o that time was ace-toace time, and >50% o the total visit time was spent counseling the patient regarding the new diagnosis, urther necessary testing, treatment options, and plans or consultants. Although only a level 2 visit is documented, since CCC is the key eature o the service, the visit can be billed based on time. The highest level o inpatient ollow-up service is a level 3 [99233] which is associated with an average visit time o 35 minutes. In Medicare patients, only ace-to- ace time can be used when determining i prolonged service time is separately reimbursable. Only 60 minutes o the total visit time was ace to ace. This means that 25 minutes o prolonged service care was provided (60 minutes total ace-to- ace time minus 35 minutes typical visit time or a level 3 ollow-up). In this scenario, those 25 minutes are not separately reimbursable. This service or a Medicare patient would be reported as a level 3 inpatient ollow-up [99233]. Reimbursement would be di erent i this patient does not have Medicare, and the insurer ollows the CPT manual. The total visit time would now be 75 minutes, adding in time spent providing care on the patient’s f oor or in their unit. Now in addition to the level 3 inpatient ollow-up visit, there are 40 minutes o prolonged service (75 minutes direct patient care time minus 35 minutes typical visit time or a level 3 inpatient ollow-up). This service would now be reported as a level 3 inpatient ollow-up [99233] PLUS the rst hour o prolonged service [99356] which would result on average in ~$95 additional income. Example 2: A non-English-speaking patient with an asthma exacerbation and lots o anxiety continues to call nursing several times during the day with shortness o breath, requiring repeated history taking, physical exam, and reassessment a ter each albuterol nebulizer treatment. In addition, each interaction with the patient requires the assistance o an interpreter. A compliant level 2 inpatient ollow-up visit [99232] is documented. Sixty minutes o aceto- ace care is provided intermittently over the course o the day. The typical visit time or 99232 is 25 minutes. Thirty- ve minutes o prolonged service that is not dominated by counseling or coordination o care is best ref ected by 99232 PLUS 99356. For Medicare, start and stop times or prolonged services and the indication or the prolonged time need to be documented along with a brie summary o what was done during that time in addition to the total ace-to- ace time providing care on that calendar date. The CPT handbook does not include a requirement or documenting start and stop times to bill or this service. There may be variable requirements among state Medicaid and private payors. 188

■ CRITICAL CARE Critical care is de ned in the Medicare Claims Processing Manual, Chapter 12, Section 30.6.12, as a physician’s direct delivery o medical care o a high-complexity MDM, to a critically ill or injured patient to prevent or stop imminent or active acute organ ailure. A critical illness or injury acutely impairs one or more vital organ systems so that there is high probability o imminent or li e threatening deterioration in the patient’s condition. Some examples o critical illness rom the Medicare manual include circulatory ailure, shock; renal, hepatic, or respiratory ailure. Chronic organ ailure management does not meet criteria or critical care services. Examples o this include chronic vent management and routine hemodialysis. For a service to quali y as critical care, all our criteria must be met and adequately documented: 1. The medical necessity re ers to a statement about the patient’s illness. The Medicare manual states “…The ailure to initiate these interventions on an urgent basis would likely result in sudden, clinically signif cant or li e threatening deterioration in the patient’s condition….” 2. The service meets criteria or high-complexity medical decision making, and the high-complexity MDM is adequately documented in the chart. 3. The care is directly urnished by the physician, not by the resident, and not by a NPP in a split/shared situation. Critical care cannot be per ormed and billed as a split/shared visit. 4. The patient has a critical condition as de ned above. Since critical care encompasses not only the “treatment o organ ailure” but also the “prevention o urther deterioration in the patient’s condition,” it is not a requirement that the person have an emergency or crisis situation to bill or critical care. The physician’s documented clinical judgment that the patient is at high risk o impending organ ailure, or urther deterioration in clinical condition, will support this criteria. Seeing a critically ill patient does not automatically allow critical care billing. For example, an ophthalmologist seeing a septic patient on pressors, or glaucoma treatment, cannot bill or critical care. There is no restriction to where critical care can be provided. It is not uncommon to provide critical care to a patient in a regular medical ward with an acute change in clinical status, while awaiting trans er to an intensive care unit. A patient is in the intensive care unit does not automatically allow or a critical care service to be billed. For example, a patient admitted to the ICU or acute respiratory ailure 7 days ago, unable to wean o the ventilator, but stable or 3 days on their current vent settings, awaiting tracheostomy, no longer meets critical illness criteria. Neither does a patient who is in the ICU due to increased nursing needs such as a patient in diabetic ketoacidosis who needs glucose nger checks every hour, and the high nurse to patient ratio on the general ward, makes this level o

Activities that cannot count toward billable critical care time include work that does not directly contribute to the patient’s care, even i per ormed at the patient’s bedside: 1. Time teaching 2. Time looking up literature 3. Family updates, even i at the request o the patient 4. Time per orming separately reimbursed procedures

TABLE 28-3 Critical Care Billing Minutes of Critical Care 0-29 30-74 75-104 105-134 135-164 165-194 195+

CPT Codes Submitted Submit appropriate E/M 99291 99291 + 99292 99291 + 99292 × 2 99291 + 99292 × 3 99291 + 99292 × 4 - - - - ollow the pattern above - - - -

C H A P T E R 2 8 C o n s u l t a t i o n , C

CPT 36000 36600 36410, 36415, 36591 43752, 91105 71010-26, 71015-26, 71020-26 Temporary transcutaneous pacing 92953 Interpretation o cardiac output indices 93561, 93562 Ventilator management 94002-94004, 94660, 94662 Pulse-oximetry 94760, 94761, 94762 Data analysis rom a computer 99090

g e m e n t , T i m e B a s e d , a n d P a l l i a t i v e C a r e B i l l i

Certain procedures when per ormed on the same date as a critical care service and by the same provider, are bundled into the reimbursement or critical care and cannot be billed or separately. (Table 28-4). Any medically necessary procedure not included in this table can be billed separately rom critical care, such as central line placement, cardiopulmonary resuscitation, and intubation to name a ew. The documentation should clearly state that the time per orming these unbundled procedures is not included in the reported critical care time. When critical care is provided by the same physician/billing group on the same date that another E/M service such as an inpatient admission, ollow-up, or consult was provided earlier in the day when the patient was not critically ill, both the earlier E/M and the critical care service can be reimbursed. The exception to this rule is when the other E/M service is an emergency room visit [9928199285]. An emergency room service cannot be paid on the same date as a critical care service by the same physician/billing group. In a coverage situation, such as a change in shi ts where a partner in the same billing group continues to provide critical care on the same calendar date, critical care time can be aggregated as long as the initial physician provided at least 30 minutes o critical care. For example, i Dr A provides 40 minutes o critical care at 6 pm and then Dr B takes over and provides an additional 35 minutes o critical care at 7 pm, the critical care time can be aggregated. A total o 75 minutes o critical care was provided; the rst hour o critical care [99291] would be submitted by Dr A and an additional hal hour o critical care [99292] would be submitted by Dr B. However, i Dr A had only provided 25 minutes o critical care and Dr B provided 50 minutes, although they still provided a total o 75 minutes o critical care, Dr A did not provide at least 30 minutes be ore going o shi t. They cannot aggregate their critical care time. Dr A would bill an appropriate E/M code that best represents their work such as an inpatient admission or ollow-up, and Dr B would bill or the rst hour o critical care [99291].

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Procedure IVplacement Arterial blood gas Blood draws, physician skill needed NG tube placement (+ luoro, +lavage) Chest x-ray, pro essional component

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1. Time spent reviewing test results while on the patient’s f oor or in their unit, and does not all into the pit all situation above. Time spent personally viewing a chest x-ray in the radiology suite on a di erent f oor or looking at a peripheral smear in the hematology lab cannot be counted toward critical care time. 2. Time spent discussing the care plan with nursing sta or other consultants. 3. Discussions with amily members or surrogates when both o these criteria are met (a) the patient lacks capacity or unable to participate in their own care and (b) the discussion directly impacts decision making. These discussions will count toward critical care time even i they occur via phone on the patient’s f oor or in their unit. However, time spent on routine updates to amily cannot be counted toward critical care services, and is not separately reimbursable. 4. Time spent per orming procedures that are bundled into critical care (Table 28-4).

TABLE 28-4 Procedures Bundled into Critical Care

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care impossible or unsa e. Critical care billing is not warranted on a patient in an ICU bed only because the hospital policy requires it or their treatment, such as an insulin drip. Critical care is a time-based service that ollows the general rules o time-based coding. Both ace-to- ace and unit/f oor time can be counted toward billable critical care time as long as the physician is in close proximity to the patient to immediately intervene or the minutes o reported critical care. I the physician is reviewing lab data on the patient’s f oor but the patient is on a di erent f oor getting a test done, in this scenario, the unit/f oor time cannot be counted toward critical care time. For time reported as critical care time, the physician must provide their entire attention to management o the critically ill patient. For example, i the physician is at the critically ill patient’s bedside while an ECG is being per ormed, and while waiting, he is multitasking and looking up labs on another patient, this time cannot be counted toward critical care time. A minimum o 30 minutes o critical care must be provided to bill or critical care services. Twenty nine minutes or less o critical care would be billed with an E/M code that best re lects the service provided, such as an admission code [99221-99223] or inpatient ollow-up code [99231-99233]. Once 30 minutes o critical care is provided, the rst hour o critical care [99291] can be billed. Each additional hal hour o critical care [99292] can be billed or therea ter (Table 28-3). In addition to time spent ace to ace with the patient taking a history and per orming a physical exam, other activities that count toward critical care time include the ollowing:

■ CONCURRENT CARE Two di erent physicians rom di erent specialties can both receive payment or critical care services on the same calendar date i there is medical necessity or each o them to provide this level o care; however, two physicians cannot get paid or the same exact same minutes o critical care. For example, i Dr A, an internal medicine hospitalist, provides 30 minutes o critical care rom 9 to 10 a m stabilizing a patient with impending respiratory ailure, and Dr B, the intensive care physician, provides critical care between 10 and 11 a m, each physician would submit a claim or the rst hour o 189

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critical care [99291]. In the event that both physicians provide care at the same time, only one physician will get paid or critical care. The other physician should submit an E/M code that best represents their work. Having di erent subspecialty designations does not automatically allow each physician to submit a claim or the rst hour o critical care. In the event that a member cross covering a patient happens to have a di erent subspecialty designation, but their role is to continue the care started by the previous physician, the work o the two physicians would be aggregated. For example, in a hospital medicine group, i Dr A is an internist and provides critical care or 30 minutes and then their partner Dr B, a cardiologist, comes on to cover the night shi t and provides an additional 30 minutes o critical care, even i the patient’s critical illness happened to be a cardiac problem, in this situation, the two physicians would aggregate their work. A total o 60 minutes o critical care was provided, which is only enough to bill or the rst hour o critical care. Only 99291 can be submitted in this scenario. When providing critical care in tandem with a resident, the only time that the physician can count toward critical care billing, is the time they personally provide critical care, or time they are physically present while the resident provides critical care. For documentation, the resident’s note can help support the high complexity o MDM. In addition to meeting all teaching physician (TP) presence and documentation criteria, and writing a valid attestation statement linking the TP’s note to the resident’s note, the TP must personally document the ollowing to bill or critical care.

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1. The patient was critically ill at the time the TP was physically present and provided the service. 2. What the critical illness is. ICD-10 codes or a critical illness must be used, or the claim will be at high risk o initial denial. 3. The nature o the treatment and management they personally provided. 4. The number o minutes o critical care that they personally provided. Documentation o the above by the resident is insu cient or billing. An example rom the Medicare manual o minimally acceptable TP documentation or critical care: “Patient developed hypotension and hypoxia; I spent 45 minutes while the patient was in this condition, providing f uids, pressor drugs, and oxygen. I reviewed the resident’s documentation and I agree with the resident’s assessment and plan o care.”

■ DISCHARGE MANAGEMENT SERVICES Discharge management services can only be billed by the primary attending o record, or a partner covering that day. All other consultants should bill an inpatient ollow-up visit [99231-99233] or an established outpatient visit [99212-99215] based on the patient’s inpatient versus observation status as well as payor rules or observation services. For inpatient discharge management, there are two levels o service: 30 minutes [99239]. Both ace-to- ace and unit/f oor time spent in discharge activities count, including but not limited to taking a history, the nal physical exam, counseling the patient and amily, reviewing data, writing prescriptions, and ordering ollow-up appointments. The only required documentation to bill or discharge management services is a statement attesting to having a ace-to- ace visit with the patient on the date o discharge management services. For legal, ethical, and high-quality patient care reasons, urther documentation o the details o that visit would be prudent. When providing the higher level o inpatient discharge management [99239], documentation must explicitly state how much time was spent on discharge management as well as a brie summary o what was done during that time. Lack o this statement will prevent 190

reimbursement or the higher level o care [99239]. No time amount needs to be documented when billing the lower level o care [99238]. I extensive amounts o time over 30 minutes are spent on discharge management, there is no additional reimbursement or this care. Prolonged services cannot be billed with any discharge management code. There is only one level o discharge management or observation services regardless o the amount o time spent on care. One o the most common documentation errors preventing reimbursement or the higher level o inpatient discharge is the statement “I spent 30 minutes on discharge management.” As opposed to other time-based services where 30 minutes is the minimum amount needed to bill a unit o service (ie, prolonged service, critical care), more than 30 minutes must be spent in discharge management to allow reimbursement or the 99239. This author suggests documenting the actual amount o time spent, in minutes. PALLIATIVE CARE Although palliative care has had its own subspecialty designation (17) since October 2009, many internal medicine hospitalists (subspecialty 11) have developed expertise in this eld without ormally changing their subspecialty designation rom 11 to 17. When unctioning as a consultant providing concurrent care to patients under the care o a colleague in the same subspecialty, there are several “best practices” to be aware o to minimize claims denials.

■ SUBSPECIALTY DESIGNATION When providing concurrent care, one o the rst pieces o evidence that medical necessity exists or two physicians to manage a patient on the same calendar date, is di erent subspecialty designations. A physician can go into the Medicare Provider Enrollment, Chain and Ownership System (PECOS) at any time and change their primary and secondary subspecialty designations. The physician should have evidence o expertise in their primary subspecialty designation; this does not have to be completion o an accredited ellowship program in that eld. Recognition at the local, regional, or national level o expertise via activities such as publications, public speaking engagements, or development o institutional protocols or curricula, would satis y this criteria. Documentation o constant and updated Continued Medical Education (CME) credit in that eld would also count. Many physicians list their primary subspecialty designation as the eld that they provide >50% o their services in. For internal medicine palliative care hospitalists, the percent o services provided as an internist may o ten outweigh that o their palliative care services; symptom-driven ICD-10 coding, complete descriptive documentation, and vigilant claims tracking are key to ensure appropriate reimbursement or these services.

■ SYMPTOM-DRIVEN ICD-10 CODING Palliative care providers are o ten consulted to assist with maximizing quality o li e and minimizing su ering or the time a patient has le t. In doing so, the goals o care o ten center around symptom control and not disease management. This may di er rom the primary attending’s care plan, which may employ palliative services, but which are still overall managing a disease state. Use o ICD-10 codes or symptoms being managed, not only better ref ects the work o the palliative care provider, but also ensures that di erent ICD-10 codes will be submitted rom the primary physician’s claim. For example, a patient with end-stage COPD is admitted or the eighth time this year with a COPD exacerbation, contemplating hospice care, and most bothered by dyspnea and atigue. The palliative care provider’s documentation and plan will ocus on control o the symptoms o dyspnea and atigue, while the primary hospitalist’s note will ocus on appropriate management o COPD. Claims or

C H A P T E R 2 8 C o n s u l t a t i o n , C o m a n e m t , T i m e B a s e d , a n d P a l l i a t i v e C a r e B i

Centers or Medicare and Medicaid Services. Medicare Claims Processing Manual: Section 30.6.1.C; Section 30.6.10, Section 30.6.12, Section 30.6.15.1 (Chapter 12). CMS Web Site. Available at www.cms.hhsgov/manuals/downloads/clm104c12.pd . Accessed December 14, 2015.

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The best way to prevent uture denials is to determine the reason or denial o a medically necessary visit, and use in ormation learned rom that encounter to prevent a denial or similar services. For example, a private insurer who sees two inpatient ollow-up services [99231-99233] rom the same subspecialty group on the same calendar date, even with di erent ICD-10’s, may deny it up ront simply because they require modi er –25 to be attached to one o the services. Another provider may require documentation to be submitted up ront or all situations where two inpatient ollow-up visits are submitted on the same date. Lessons learned rom these two denials alone may prevent hundreds more.

CPT 2015: Current Procedural Terminology. Cpt/Current Procedural Terminology Pro essional Edition. American Medical Association Press.

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SUGGESTED READINGS

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Palliative care providers o ten spend enormous amounts o time counseling patients, and may bill a signi cant percent o their visits based on CCC. More detailed descriptions o the clinical situation will better support the medical necessity to spend these larger amounts o time with the patient. Adjectives may make a huge di erence. A statement such as “patient extremely distraught over their terminal condition and required intense counseling regarding goals o end o li e care” paints a much better picture or the need or 90 minutes o counseling than a statement like “Patient upset over terminal diagnosis. I counseled the patient on goals o care.”

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One way to help track these services internally would be to remember to submit ICD-10 code [Z51.5] or “encounter or palliative care services” with 100% o these services. This code should never be the primary diagnosis. Its use will not alter the amount o reimbursement or the visit; however its presence on a claim may alert an insurer that this service is separate and distinct rom another E/M submitted by the same billing group, and prevent an up ront denial. At minimum, it will allow a physician to more easily search or these encounters in their data base to monitor payment or these services.

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these services will be submitted with the ICD-10 codes or dyspnea [R06.0] and atigue [R53.83], and COPD [J44.1] respectively.

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Billing for Procedures and Use of Modifiers in Inpatient Practice Yvette M. Cua, MD

PROCEDURES

■ INTRODUCTION Procedures are commonplace in hospital medicine; more and more hospitalists have invested additional educational time in becoming pro cient in per orming them. Understanding the documentation requirements necessary to ensure proper payment o procedures, including adequate documentation o the medical necessity to per orm them, is crucial. In addition, making sure that the Current Procedural Terminology (CPT) code is correctly linked to the proper International Classi cation o Diseases, 10th Revision (ICD-10) code(s) will urther prevent claim denials. Details regarding the service requirements o each procedure are outlined in the CPT Handbook, published by the American Medical Association. The Medicare Claims Processing Manuel discusses nuances in Medicare guidelines regarding situational and documentation requirements or reimbursement. Procedures may be described as “minor” or “major.” These terms have caused signi cant con usion in the literature. There are actually two di erent ways in which the terms “minor” and “major” procedures are used within the Medicare manual.

■ MINOR VERSUS MAJOR PROCEDURES Surgeries and global packages Within the Medicare Processing Manual, procedures are re erred to as “surgeries” or “surgical procedures.” When discussing payment or the medically necessary care provided immediately be ore and a ter the procedure, one must be aware o the global period associated with the service. Services with global periods o 90 days are de ned as “major surgeries” or “major procedures.” These terms are used interchangeably in the manual. Services with global periods o 0 or 10 days are described as “minor surgeries” or “minor procedures.” Endoscopies are included in this category. Most procedures per ormed by nonsurgical specialties all into the “minor” procedure category. One example o the importance o this distinction is use o modi er –57 (decision to per orm surgery). Modi er –57 is only used when deciding to per orm major and not minor procedures. Reimbursement or all care related to the surgery, by the surgeon per orming the procedure, occurring 1 day be ore the procedure and or the ensuing 90-day global period, is bundled into the reimbursement or the surgery’s CPT code. One exception is the reimbursement or the E/M visit at which time the decision to operate is made i it occurs 1 day prior to surgery or on the day o surgery. Modi er –57 attached to that E/M code will allow or its reimbursement in addition to the reimbursement or the major procedure. For the situation where the decision to per orm a minor procedure is made at an E/M visit the same day o the procedure, modi er –25 should be attached to that E/M code to show that it was medically necessary work, separate rom the usual history and physical needed to sa ely per orm the procedure. Teaching physician procedural billing With regard to teaching physician (TP) rules or procedural billing, a “minor” procedure is de ned as taking 5 minutes. The TP must be present or the critical or key portion(s) o the procedure and must be immediately 192

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Central venous access can be achieved through various locations and processes, and with various apparatuses. Di erent CPT codes exist based on the ollowing key pieces o in ormation: (1) location o access—central, peripheral; (2) method o placement—tunneled, nontunneled; (3) apparatus—catheter, port, pump; (4) number o access sites in the apparatus; and (5) age o the patient. Each o these actors plays a role in determining the usual amount o work needed to per orm the service, which directly ties into graded reimbursement amounts. For example, tunneled catheters require more expertise and take longer to place than nontunneled lines; centrally placed lines are more challenging than their peripherally placed counterparts; and a device with a port takes more work to place than a catheter without one. There are separate codes or repair, replacement, and removal o these apparatuses as well (Table 29-1). These central venous catheters (CVC), also called “central lines,” and central venous access devices (CVAD), like “ports,” have tips that

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terminate in either the subclavian, brachiocephalic, innominate or iliac veins, or where one o these joins with the superior or in erior vena cava. Medical documentation should include these key pieces o in ormation not only to select the correct CPT code, but also to adequately support reimbursement or these services. This in ormation is usually ound in a procedure note. “Placing a central line” at bedside, by convention, has become synonymous with “placing a nontunneled catheter in a central location” such as the internal jugular vein or the subclavian vein. This corresponds to CPT codes [36555, 36556] which di er only by the age o the patient. In this example, to ensure accurate CPT code selection, at minimum, the body o the procedure note should include re erence to insertion o a nontunneled catheter (such as a triple lumen) into a central vessel (such as the right subclavian). In addition, postprocedure chest x-ray results veri ying tip location should be documented. The CPT codes or peripherally inserted central catheter (PICC) placement [36568, 36569] only di er by age o the patient. Use o ultrasound guidance [76937] or uoroscopy [77001] or placement, is reimbursed through an additional code and is not bundled into the reimbursement or central line placement. Billing or imaging used to guide line placement requires very speci c documentation. Ultrasound guidance or central vascular access [76937] is only reimbursable when used with a “dynamic” technique and not a “static” technique. A dynamic technique implies that the ultrasound is used throughout the entire procedure, not only to identi y the target vessel, but to watch success ul entrance o the needle into it. “Static” use o the ultrasound purely identi es the vessel and its patency, and is not reimbursable.

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available or the entire procedure, in order to bill or it. The de nition o “major” and “minor” in this context is based on the usual total procedure time. Examples o minor procedures include drainage o a subungal hematoma [11740], or a skin punch biopsy [11100]. Most inpatient procedures hospitalists per orm, are considered “major” procedures, such as central line placement [36555-36556], thoracentesis [32554, 32555], or lumbar puncture [66270, 66272].

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TABLE 29-1 CPT Codes for Central Venous Access Procedures Type CVC

Tunneled

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2-Tunneled cath

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Peripherally Placed Method Nontunneled

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Tunneled

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CPT 76937

Age 10 units Procedure type • Trauma surgery • Emergency surgery • Vascular, cardiac surgery, cardiopulmonary bypass • Obstetrical • Orthopedic surgery • Liver surgery • Prostate • Tonsillectomy Perioperative medications • Antiplatelet agents • Anticoagulants Hypothermia (T < 35°C)

The degree o resuscitation in the bleeding patient depends on the suspected pace o the bleeding and degree o end organ e ect. Therapy should be guided by physiologic endpoints such as heart rate, blood pressure, urine output, oxygen saturation, end-organ per usion, and electrocardiography. More advanced monitoring including echocardiography and invasive hemodynamic measurements may be needed i the patient is not responding or is clinically unstable. Hypothermia can exacerbate and complicate surgical bleeding due to the enzymatic reactions o coagulation inhibition by low temperatures. The patient should be made normothermic through the use o warm IV uids, warming blankets, or warming devices. Additionally, any electrolytes should be corrected, particularly calcium and acidosis, to maintain an optimal milieu or coagulation reactions to occur. Additional interventions should be undertaken based on the results o coagulation studies (Table 43-1), and blood products should be administered in conjunction with clinical assessment and based on the American Society o Anesthesia (ASA) guidelines or perioperative bleeding (Table 43-4). Patients with qualitative platelet dys unction (who have been taking antiplatelet agents or have uremia) may require desmopressin, which can partially reverse the platelet dys unction. Tranexamic acid (TXA) is an agent with some utility in ameliorating perioperative

Ge ne ral Me as ure s

Pos t-ope ra tive ble e ding

He modyna mic S ta tus A, B, C’s, Vita l S igns His tory from prima ry nurs e

Uns table

S table

In a ddition to “STABLE” inte rve ntions, a ls o do the following: Reve rs e coa gulopa thy (if pre s e nt) S ta rt va s opre s s ors for hypote ns ion re fra ctory to volume re s us cita tion Pre pa re for pos s ible re turn to OR or e mboliza tion (if fe a s ible )

Ens ure IV a cce s s Atte mpt to loca te s ource of ble e ding Be ing volume re s us cita tion Tra ns fus e blood products (if ne e de d) Hold a ge nts a ffe cting coa gula tion (ris k/be ne fit mus t be eva lua te d) Notify s urge on

Vis ible ble e ding

Co ag ulo pathic ble e ding

No n-vis ible ble e ding

Control loca l ble e ding (be ds ide or OR) Apply pre s s ure Topica l he mos ta tic a ge nt/ca ute ry S uture liga tion

Re pla ce de ficie nt fa ctors (if ide ntifie d) S pe cific reve rs a l a ge nts : DDAVP for ure mia /pla te le t dis orde rs Prota mine for He pa rin S pe cific reve rs a l a ge nt or P CC for NOAC Vita min K/FFP /P CC for VKA’s Cryopre cipita te for DIC

S e ria l exa mina tions Eva lua te for compa rtme nt syndrome Abdomina l Extre mity Ima ging s tudie s Che s t ra diogra ph CT s ca n Angiogra phy

Wo rs e ning e xam o r c o nc e rning imag ing finding s : Ope ra tive explora tion or e mboliza tion (if fe a s ible )

Figure 43 1 Approach to managing postoperative bleeding. 290

Monitor urine output Review ope ra tive re port Ma inta in te mpe ra ture >35*C Review me dica tions (pa rticula rly a ntipla te le t/a nticoa gula tion) Obta in La bora tory Te s ts : Type a nd cros s -ma tch He moglobin/he ma tocrit/pla te le ts Ele ctrolyte s Re na l/he pa tic/coa gula tion function Fibrinoge n (if DIC s us pe cte d) EKG a nd bioma rke rs (if ca rdia c is che mia s us pe cte d)

C H A P T E R 4 3 P e r i o p e r a t i v e H e m o

bleeding; however, it is associated with the risk o thrombosis, and its use should be decided upon in conjunction with the surgeon. For patients who have received intraoperative un ractionated heparin (UFH) administration within 6 to 12 hours o the bleeding, it should be reversed with the use o protamine, and the activated clotting time (ACT) can guide the appropriate dosage. Protamine can also reverse the e ects o low-molecular weight heparins, but it is less e ective than it is or UFH. Coagulopathy rom war arin should be reversed with resh rozen plasma and/or vitamin K. Prothrombin concentrate complex (PCC) contains vitamin K-dependent clotting actors and can be used or urgent correction o bleeding associated with acquired coagulation actor de ciency. Recombinant actor VII can also be e ective in ameliorating bleeding associated with acquired coagulation actor de ciency; however, it is very expensive and is associated with a risk o thrombosis. Its use should be decided upon in conjunction with the surgeon. The newer oral direct actor inhibitors include actor Xa inhibitors and direct thrombin inhibitors. They pose challenges due to lack o routine laboratory testing to monitor their e ect on coagulation, and lack o speci c reversal agents; as such, these drugs should be stopped 3 to 5 days prior to major surgery. I bleeding does occur on these agents, traditional measures to control bleeding locally should be employed such as direct pressure, topical hemostatic agents, cuatery, or embolization. Due to their short hal -lives, stopping the agent and providing expectant support is usually suf cient in minor bleeding. In cases o more severe hemorrhage; speci c or non-speci c reversal agent should be employed to abate bleeding. See Chapter 78 “Bleeding and Coagulopathy” and Chapter 57, “Postoperative Blood Trans usion.”

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Central nervous system surgeries: platelets 1.5.

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Postoperative bleeding is a serious surgical complication. Preoperative evaluation can help determine which patients present the highest risk o su ering this complication. Bleeding should be considered in any postoperative patients with tachycardia, hypotension, oliguria, or evidence o shock. Postoperative bleeding may be medical, surgical, or both. Physical exam and laboratory tests should guide a ocused management o the problem, and resuscitation should be initiated immediately. The surgical team should be involved in the work-up and decision making as soon as postoperative bleeding is suspected.

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CONCLUSION

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≥100,000 cells/mm 3 Normal values

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Therapy Packed red blood cells Platelets Fresh rozen plasma Cryoprecipitate

Laboratory Value Indicates need for Transfusion Hemoglobin ≤6 g/dL ≤50,000 cells/mm 3* INR ≥ 2.0*

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TABLE 43-4 American Society of Anesthesiologists (ASA) Guidelines for Perioperative Transfusion in Excessive Bleeding

pressure, or with bedside cautery. Gauze applied to the bleeding wound with constant, continuous pressure maintained or 10 minutes is usually e ective. A ter 10 minutes, pressure can be released and the wound reassessed—i bleeding has not stopped then pressure should be reapplied and the surgeon should be noti ed. Deep surgical bleeding requires prompt evaluation by a surgeon so that exploration and de nitive control o the culprit blood vessel can be established. Invasive interventions are likely required in cases o postoperative hemodynamic instability, hemothorax, hemoperitoneum and compartment syndromes.

SUGGESTED READINGS Bougle A, Harrois A, Duranteay J. Resuscitative strategies in traumatic hemorrhagic shock. Ann Intensive Care. 2013;3(1):1. Hammond KL, Margolin DA. Surgical hemorrhage, damage control, and the abdominal compartment syndrome. Clin Colon Rectal Surg. 2006;19:188-194. Hunt BJ. Bleeding and coagulopathies in critical care. N Engl J Med. 2014;370:847-859. Ker K, Prieto-Merino D, Roberts I. Systematic review, meta-analysis and meta-regression on the e ect o tranexamic acid on surgical blood loss. Br J Surg. 2013;100:1271-1279. Levy JH, Faraoni D, Spring JL. Managing new oral anticoagulants in the perioperative and intensive care unit setting. Anesthesiology. 2013;118:1466-1474. Practice Guidelines or Perioperative Blood Management. An updated report by the American Society o Anesthesiologists Task Force on perioperative blood management. Anesthesiology. 2015;122:241-300. Phillips LE, Zatta AJ, Schembri NL, Noone AK, Isbister J. Uncontrolled bleeding in surgical patients: the role o recombinant activated actor VIIa. Curr Drug Targets. 2009;10(8):744-770.

■ SURGICAL MANAGEMENT

Shah A, Stanworth SJ, McKenchnie S. Evidence and triggers or the trans usion o blood and blood products. Anaesthesia. 2015;70(Suppl 1):10-19.

Visible bleeding rom a surgical wound itsel may represent a small “skin bleeder” that can be managed with a stitch, by holding direct

Spinella PC, Holcomb JB. Resuscitation and trans usion principles or traumatic hemorrhagic shock. Blood Rev. 2009;23(6):231-240.

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CHAP TER

Postoperative Complications Peter Najjar, MD Allan B. Peetz, MD

INTRODUCTION Postoperative complications are common and costly. Recent studies suggest that, on average, each avoidable surgical complication costs payers >$10,000. Their incidence, risk actors, and impact on patient outcomes are as varied as the eld o surgery itsel . Surgical site in ections (SSIs) alone a ect >500,000 patients annually and are associated a 2 to 11 times increase in the risk o postoperative mortality. Good communication among all providers caring or surgical patients is undamental to both the prevention and management o surgical complications. Hospitalists caring or surgical patients should, accordingly, understand what surgical procedure was perormed, the indication or the procedure, and any perioperative concerns rom the operating surgeon, based on the circumstances o that particular patient or procedure. This chapter will review some o the more common postoperative complications that a hospitalist needs to recognize and manage. Each section will review the risk actors o the complication, how to mitigate those risks in the perioperative period, and how the hospitalist should identi y and manage such complications. Elective procedures provide more o an opportunity to identi y and mitigate risk actors be ore surgery, although an attempt should take place be ore any surgery (even urgent or emergent). A thorough history and physical examination should aim to identi y risks outlined in this chapter, and optimize the risk-bene t pro le o the procedure. For example, when deciding whether to hold antiplatelet or anticoagulation medications in patients with cardiac indications, the risk o cardiac complications is weighed against the risk o bleeding. This decision making should occur in concert with the surgeon, and with the patient, to ensure all parties have a common understanding o the risks and the bene ts o the surgery.

PRACTICE POINT

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Prevention o postoperative complications begins in the preoperative period. Surgical complications are common and costly; interdisciplinary teams must work together on their prevention and management.

COMMON COMPLICATIONS WITHIN THE POST ANESTHESIA CARE UNIT (PACU) A ter surgery, patients usually stay in a postanesthesia care unit (PACU) or close monitoring while they recover rom the e ects o anesthesia. Common problems managed in the PACU include postoperative pain, hyper- and hypotension, respiratory insu ciency, and nausea and vomiting.

■ POSTOPERATIVE PAIN Patients in this phase o care are o ten unable to verbalize pain due to e ects o anesthesia; accordingly, pain assessments are o ten based on other objective assessments such as blood pressure, heart rate, respiratory rate and signs o agitation. See Chapter 48 (Perioperative Pain Management).

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■ POSTOPERATIVE HYPER- AND HYPOTENSION

C H A P T E R 4 4 e r a t i v e C o m p l i c a t i o

Postoperative nausea and vomiting (PONV) is also common in the PACU, the causes o which are multi actorial. Prior history is the most signi cant risk actor; other risk actors include longer duration procedures, use o volatile anesthetics (such as isof urane), and procedures involving the inner ear, eye, and abdominal viscera. Patients at moderate to high risk o PONVbene t rom prophylactic antiemetics, motility agents, or a scopolamine patch be ore emerging rom anesthesia.

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Intravascular volume depletion may occur concurrently with pulmonary edema due to increased vascular permeability associated with perioperative inf ammation; administration o diuretics or postoperative pulmonary edema can exacerbate intravascular depletion, hypotension, and inadequate endorgan per usion. Postoperative oliguria (less than the equivalent o 0.5 cc/kg/h) requires urgent evaluation.

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Low urine output in the immediate postoperative setting

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Pain and elevated catecholamines can contribute to hypertension and tachycardia. β-blockers should be continued in the perioperative setting or patients who took them preoperatively. Hypertension in the PACU is most commonly caused by pain and/or a history o hypertension. Certain procedures, such as carotid endarterectomy, require immediate and aggressive control o systolic blood pressure regardless o etiology to avoid catastrophic vascular, cardiac, or neurologic complications. Invasive monitoring with an arterial line may be necessary or such patients. Clear communication with the surgical team regarding target blood pressure is essential and hemodynamic agents including vasodilators and negative chrono- and inotropes are requently used as rst-line agents in these settings. Absent an indication or strict hemodynamic control, the patient should be assessed or pain and treated appropriately be ore treating blood pressure directly. For patients with pre-existing hypertension requiring medication, it is generally most appropriate to gradually reintroduce the preoperative antihypertensive regimen with the exception o diuretics in the immediate postoperative period. Hypotension in the PACU is usually due to hypovolemia, narcotic and benzodiazepine administration, or epidural anesthesia; postoperative bleeding must also be considered. Markers or hypovolemia include low urine output, signs o shock, and altered mental status, which can be masked by the residual e ects o anesthesia. Invasive monitoring with a urinary catheter, central line, or arterial line should be utilized i a patient remains hypotensive despite initial resuscitation with crystalloid. Epidural anesthesia can cause hypotension by blunting sympathetic tone and decreasing vascular resistance. In the absence o hypovolemia, however, epidurals do not usually cause hypotension. Treatment o epidural-related hypotension should include administration o a f uid bolus; temporarily holding the anesthetic in usion can also be help ul until euvolemia is obtained.

PRACTICE POINT

POSTOPERATIVE FEVER Low-grade evers in the rst 48 hours a ter surgery are a normal sequelae o inf ammation, atelectasis, or hematoma absorption ollowing surgery, and usually not rom an in ectious process. In the absence o any localizing signs or symptoms, sel -limited ever within the rst 48 hours postoperatively usually does not need in ectious work-up. A ter 48 hours, temperatures greater than 38.5°C should prompt a complete ever workup. In the postoperative patient, the surgical wound and site o venous access are potential sources o in ection and need to be care ully examined. See Chapter 206 (Undiagnosed Fever in Hospitalized Patients).

■ POSTOPERATIVE RESPIRATORY INSUFFICIENCY Although most patients will require some supplemental oxygen immediately a ter surgery, dyspnea, tachypnea, wheezing, and signs o respiratory distress are not normal postoperative signs and symptoms, and need to be addressed in the PACU. The causes and degree o risk o postoperative respiratory insu iciency are complex and patient speci ic, but all patients recovering rom anesthesia require close monitoring o their respiratory status, with personnel and equipment or reintubation readily available. The primary actors that contribute to postoperative respiratory insu iciency include use o general anesthesia, upper abdominal and thoracic surgeries, longer duration surgeries, use o endotracheal intubation, and use o narcotics. Signi icant pain also puts patients at increased risk, as pain impairs respiratory unction by limiting vital capacity and can result in hypoxia and dyspnea. Pulmonary edema is a common etiology or respiratory distress in the postoperative period, o ten secondary to the e ects o f uid shi ts and sometimes overload rom intraoperative resuscitation. Initial evaluation o pulmonary edema should include physical exam and chest x-ray; some patients may need urther work-up or evaluation by a cardiologist. Pneumothorax should be considered in patients with a central line recently placed, and should also be evaluated with a Chest x-ray. For patients with a postoperative chest tube (usually cardiac or thoracic surgery patients) a poorly unctioning chest tube or residual pneumothorax can also cause or exacerbate respiratory distress. This can be detected by physical exam and con rmed with a chest x-ray ollowed by prompt contact with the operating surgeon to relay the concern.

SURGICAL SITE INFECTIONS Surgical site in ections (SSIs) account or approximately 30% o nosocomial in ections and are the most common in ections a ter surgery. They are associated with a 7-day increased length o stay and cost $400 or a super cial SSI and $30,000 or organ space SSIs. SSIs are classi ed as super cial, deep, or organ space in ections. Super cial in ections are wound in ections involving the skin and subcutaneous tissues. Deep in ections involve the ascia or muscle below. Organ space in ections involve organs below the cutaneous and muscular layers (Figure 44-1).

PRACTICE POINT Wound infections

• • • •

Despite the most rigorous aseptic technique, all wounds are contaminated to some degree and have some risk o in ection. Even “clean”wounds have a 1.5% risk o in ection (Table 44-1). Wound in ections commonly occur between 5 and 10 days a ter an operation. Antibiotics are not necessary or simple wounds that have been drained. Deep space in ections usually require drainage; antibiotics alone are insu cient.

Risk actors or wound in ection are patient and operation dependent. Patient related risk actors include large body habitus, 293

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Deep space in ections occur in enclosed spaces with some degree o isolation rom blood supply, making them relatively impervious to antibiotics. Such in ections usually require drainage either percutaneously or in the operating room. Anastomotic leaks typically occur between postoperative days 5 and 7 and should be suspected in surgical patients with tachycardia, abdominal pain, ever, and elevated white count. This constellation o symptoms a ter an enteric anastomosis should prompt a CT scan. These leaks can o ten be managed with percutaneous drainage, but inability to control the in ection may require operative drainage.

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Figure 44 1 Categories of surgical site infections.

diabetes, disability, immunosuppression, malnutrition, and smoking. Certain operations, such as those involving the colon or small bowel, are higher risk than others. Other operative risk actors include operating room conditions, surgical technique (eg, laparoscopic or open), administration o antibiotic prophylaxis, and hypoxia or hypotension during the procedure. Prophylactic antibiotics are very e ective at reducing the risk o SSIs; they should be administered within 1 hour o incision and continued or no more than 24 hours a ter surgery. In the event o signi cant contamination in the OR, wounds may be le t open and managed with delayed primary closure or wet to dry dressings. The hallmarks o a wound in ection are ever, pain, tenderness, or purulent drainage. The typical presentation is between 5 and 10 days postoperatively. Some in ections can present earlier; clostridial necrotizing wound in ection should be suspected when a patient has a very high ever in the immediate postoperative period; these require immediate surgical evaluation and drainage. TABLE 44-1 Surgical Wound Classification Wound Classification Clean No in ection or in lammation Respiratory, gastrointestinal, biliary, and urinary tracts not entered Clean contaminated Entry into respiratory, biliary, gastrointestinal, urinary tracts with minimal spillage No evidence o in ection or major break in aseptic technique Contaminated In lammation, gross spillage rom GI tract, break in technique Fresh traumatic wound Dirty or infected Purulent drainage, ecal contamination, per orated viscous, delayed or contaminated traumatic wound, presence o devitalized tissue

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Infection Risk Procedure Type 1.5% Vascular surgery

10%

Appendectomy

20%

Foreign body in a wound

40%

Abscess, per orated viscous

Wounds typically heal to a maximum o 80% o the tensile strength within 6 weeks among healthy, well-nourished patients. Because o this, most surgeons restrict postoperative activities to avoid stress on the wound or 4 to 6 weeks. Wounds that have been closed primarily should be kept clean, dry, and covered or a minimum o 48 hours a ter surgery. Dry, sterile operative dressings may be kept in place until postoperative day 2; therea ter, patients can usually shower without submerging the wound. Wound dehiscence is disruption o any layer o the surgical wound. This rare complication results rom increased pressure on the wound and can arise or a variety o reasons. Suspected dehiscence should be promptly evaluated by a surgeon and may require a return to the operating room. Poor wound healing o ten leads to dehiscence. Malnutrition, liver disease, diabetes, immunosuppression, and chronic steroid use inhibit normal wound healing and are risk actors. The most common layers involved are the skin and ascia. Sudden output o serosanguinous f uid rom the wound is usually the rst sign o dehiscence. There ore, daily evaluation by multiple team members (including surgeons, hospitalists, and nurses) may help identi y subtle changes that may be harbingers o dehiscence. The management o postoperative wound dehiscence depends on the size and location o the wound as well as the patient’s condition. Fascial dehiscence—separation o the deepest layer o the abdominal wall—typically requires urgent closure in the operating room. In the most severe o cases, dehiscence leads to extrusion o intra-abdominal contents (eg, evisceration). Evisceration is a surgical emergency that requires immediate return to operating room. Hematomas are more common, and can be caused either by inadequate hemostasis during surgery or disruption o hemostasis postoperatively; risk actors or hematomas include bleeding disorders and anticoagulant use. A hematoma can result in wound elevation, pressure, pain, dehiscence, and in ection. The surgeon should always be alerted i there is a suspected hematoma; depending on the size and location, treatment can vary rom watch ul waiting to re-exploration in the OR. Hematomas ollowing neck exploration may rapidly compromise the airway in the postoperative period. Precipitating actors include abrupt increases in intrathoracic pressure rom coughing, emesis, or Valsalva maneuvers. Treatment involves emergent evacuation o the hematoma prior to reintubation. Seromas are collections o serous f uid that orm a ter procedures involving disrupted lymphatic f ow and raised skin f aps. They are generally the result o a normal physiologic response to anatomic dead space, and their incidence is dependent on the anatomic location o the wound. Examples o procedures commonly associated with seromas include inguinal hernia repair, groin exploration, and mastectomy. Suction drains may be le t in place at the end o the procedure to increase tissue apposition and remove f uid. Compression dressings can also reduce the risk o seroma ormation. Seromas may increase the risk or wound disruption and in ection but are usually nothing more than a nuisance. Management may be expectant or include serial aspirations. Rarely, return to the OR is indicated to ligate contributing lymphatics.

DELIRIUM Postoperative delirium is most common in patients with advanced age, a history o sensitivity to narcotics or anesthetics, heavy alcohol use, dementia or prior delirium. Delirium can occur a ter any surgical procedure, but is most common a ter cardiovascular and thoracic surgery. The causes are multi actorial, including a myriad o medications, loss o environmental cues, insomnia, and recovery rom cardiopulmonary bypass. Delirium presents with waxing and waning severity with periods o lucidity, recurrent con usion, agitation, hallucination, and con abulations. These patients may present a risk to themselves and others by trying to get out o bed without assistance, or trying to remove tubes and drains. Prevention is the best strategy and entails maintaining a regular sleep-wake cycle, restoring environmental cues (such as daylight and clocks), and removing extraneous environmental stressors (minimizing bright lights and loud noises). Some patients will respond well to reassurance and emotional support. I at risk or sel -harm, lowdose antipsychotics are rst line agents. It is best to start at low doses and titrate up as needed, as these medications can be sedating, may worsen delirium at higher doses, and may inter ere with pulmonary unction and physical therapy. These pharmacologic treatments may provide symptom control but do not treat the underlying causes o delirium and at times can exacerbate delirium. When managing patients with postoperative delirium it is also important to rule out other organic disease triggers such as sepsis, stroke, or metabolic derangements. See Chapter 81 (Delirium). DEEP VENOUS THROMBOSIS AND PULMONARY EMBOLUS Venous thromboembolism (VTE) is a leading cause o preventable death in the postoperative setting. Surgical patients are at high risk or VTE due to the surgical procedure itsel as well as induction o

C H A P T E R 4 4 P o s t o p e r a t i v e C o m p l i c a t

URINARY TRACT INFECTIONS (UTI) Urinary tract in ections (UTI) are most common a ter vaginal or urologic surgery and any surgery with the use o indwelling catheters. Women and obese patients are at highest risk. The most common pathogens are Escherichia coli, Staphylococcus saprophyticus, and Proteus mirabilis. However, hospitalized and immunosuppressed patients are also susceptible to Klebsiella, Proteus vulgaris, Candida albicans, and Pseudomonas. The standard or prevention is the removal o indwelling catheters within 48 hours o insertion. The need or continued urinary catheterization should be assessed at least daily to prevent needless prolongation o catheter placement and increased risk o catheter-associated UTI. Criteria or diagnosis and treatment are the same as or UTIs in the nonpostoperative period. See Chapter 197 (Urinary Tract In ection and Pyelonephritis).

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Postoperative ileus is expected a ter gastrointestinal surgery but is also common a ter other procedures, usually due to narcotic use and/or immobility. Ileus usually presents with abdominal distention, nausea, belching, and inability to pass f atus. Resolution o the symptoms usually occurs within 5 days o surgery but can be longer, particularly in debilitated patients or those with signi cant narcotic use. Classically, an ileus on plain abdominal x-ray is associated with uni orm distribution o air throughout the bowel, but this nding is not speci c. Abdominal CT scan with enteric contrast has close to 100% sensitivity and speci city in distinguishing postoperative obstruction rom ileus. Colonic pseudo-obstruction is a rare postoperative complication, and most likely occurs in older patients with prolonged immobility, preoperative institutionalization and unctional limitation. It more commonly occurs a ter orthopedic surgeries than other types o surgeries. Patients present with signs o an ileus, and radiographs demonstrate a decompressed small bowel and uni ormly dilated colon. Treatment involves hydration, bowel rest, and decompression (distally with rectal tube placement and proximally with nasogastric tube placement i there is evidence o gastric distension). In re ractory cases, neostigmine is an option but can be associated with bradycardia. I the cecum is dilated >11 cm, additional measures should be undertaken to avoid per oration, such as a cecostomy tube or a cecal resection. General surgeons should be engaged early in the management o suspected postoperative colonic pseudo-obstruction.

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GASTROINTESTINAL COMPLICATIONS

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See Chapters 60 (Pulmonary Complications) and 59 (Cardiac Complications).

general anesthesia, which results in prolonged immobility, hypercoagulability, and endothelial damage. Patients with known hypercoaguable states, prior VTE, and malignancy are at especially high risk. High-risk surgical procedures include orthopedic surgery, trauma, and neurosurgical treatment o head injury and brain tumors. Prophylaxis starts be ore surgery with the application o pneumatic compression devices and subcutaneous heparin 2 hours prior to anesthetic induction. In the absence o procedure- or patientspeci c concerns, pharmaceutical prophylaxis should not be held preoperatively. Unless there are clear contraindications, such as increased bleeding risk, patients should receive pharmacologic prophylaxis and pneumatic boots throughout and perioperative period. See Chapter 56 (VTE Prophylaxis or Patients Requiring NonOrthopedic Surgery). Pulmonary embolus (PE) still causes considerable mortality in hospitalized patients. PE should be suspected in all surgical patients presenting with symptoms o dyspnea, tachycardia, and hypoxemia. The decision to start anticoagulation should be made with the operating surgeon, while pending urther diagnostic testing. See Chapter 253 (Diagnosis and Treatment o VTE).

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POSTOPERATIVE URINARY RETENTION Postoperative is common but rarely prolonged. Common risk actors or postoperative urinary retention include male sex, prostatic enlargement, epidural/spinal/prolonged anesthesia, use o antihistamines or narcotics, and pelvic/perineal procedures. An overdistended bladder (>500 mL) and disruption o the neural pathways that control voiding impairs urinary contraction and micturition. Prophylactic catheterization in the operating room is recommended or any procedure lasting more than 3 hours, or when interruption o the sacral plexus is anticipated (eg, abdominoperineal resection). I a catheter is not present, patients should be encouraged to void soon a ter the procedure. I the patient has not voided or more than 6 hours, it is appropriate to evaluate retention with a bedside ultrasound; alternatively, an in-out catheter may be used to determine the extent o retention. The treatment or bladder distention is intermittent catheterization along with mitigation o any contributing actors. Some patients may have prolonged urinary retention in the postoperative period (>48 hours). In this scenario, appropriate pharmacologic treatment should be initiated and an indwelling Foley catheter should be placed. Some may require subsequent outpatient urologic ollow-up or a void trial a ter discharge. See Chapter 67 (Urology). CONCLUSION Postoperative complications are associated with signi cant morbidity, prolonged length o stay, and hospital costs. Hospitalists should know how to identi y and manage the most common postoperative complications. Comprehensive assessment preoperatively, 295

P A R T

Güldner A, Pelosi P, De abreu MG. Nonventilatory strategies to prevent postoperative pulmonary complications. Curr Opin Anaesthesiol. 2013;26(2):141-151.

SUGGESTED READINGS

Najjar PA, Smink DS. Prophylactic antibiotics and prevention o surgical site in ections. Surg Clin North Am. 2015;95(2):269-283.

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attention to surgical technique and anesthetic management, and a multidisciplinary approach to medication management, in ection control, and patient mobility can reduce the risk o surgical complications.

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Arozullah AM, Khuri SF, Henderson WG, et al. Development and validation o a Multi actorial risk index or predicting postoperative pneumonia a ter major noncardiac surgery. Ann Intern Med. 2001;135:847-857.

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Mattei P, Rombeau JL. Review o the pathophysiology and management o postoperative ileus. World J Surg. 2006;30(8):1382-1391.

45

CHAP TER

Surgical Tubes and Drains Alexandra Columbus, MD Joaquim M. Havens, MD Allan B. Peetz, MD

INTRODUCTION Surgical drains are used to monitor or postoperative leaks or abscesses, collect normal physiologic uid, or to minimize dead space. Table 45-1 lists various types o drains, with their indications or use. This chapter will review the most common types o surgical drains, and the basic care o these drains rom a hospitalist perspective.

PRACTICE POINT

•

Hospitalists should know the location and purpose o all surgical drains in their patients, but should not manipulate these drains without input rom the surgeon who placed them.

CHEST TUBES Chest tubes are placed in the pleural space to evacuate air or uid. They can be as thin as 20 French or as thick as 40 French ( or adults). Chest tubes are typically placed between the ourth and th intercostal spaces in the anterior axillary or mid-axillary line, however, location may vary according to the indication or placement. The tubes can be straight or angled. The tubes are connected to a collecting system with a three-way chamber. The water chamber holds a column o water which prevents air rom being sucked into the pleural space with inhalation. The suction chamber can be attached to continuous wall suction to remove air or uid, or it can be placed on “water seal” with no active suction mechanism. The third chamber is the collection chamber or uid drainage. Indications or a chest tube include pneumothorax, hemothorax, or a persistent or large pleural e usion. Pneumothorax and hemothorax usually require immediate chest tube placement. Chest tubes are also commonly placed at the end o thoracic surgeries, to allow or appropriate re-expansion o the lung tissue. A chest x-ray should be obtained a ter any chest tube insertion to ensure appropriate location. Chest tubes are equipped with a radiopaque line along the longitudinal axis, which should be visible on x-ray. Respiratory variation in the uid in the collecting tube, called “tidling,” should also be seen in a correctly placed chest tube, and should be monitored at the bedside to reassure continued appropriate location. The interventional radiologist or surgeon who placed the tube should determine the subsequent requency o serial chest x-rays required to monitor the location o the chest tube. I the patient has a pneumothorax, air bubbles will be visible in the water chamber (called an “air leak”) which is o ten more apparent when the patient coughs. The chest tube should initially be set to continuous suction at –20 mm Hg to evacuate the air. Once the “air leak” has stopped, the chest tube should be placed on water seal to con rm the pneumothorax is resolved (water seal mimics normal physiology). I the pneumothorax is not resolved, the chest tube should be placed back on continuous suction. A chest x-ray should be obtained anytime the chest tube is changed rom suction to water seal or vice versa. I the patient experiences ongoing or worsening pain, ever, or inadequate drainage, a chest computed tomographic (CT) scan may be warranted to identi y inappropriate positioning or other complications, such as occlusion or e usion, o the tube. Chest tubes may become clogged by blood or other debris; the surgical team may be able to evacuate the tube with suction tubing at the bedside. I unsuccess ul, the tube may need to be removed and reinserted. 297

Type Chest tube

Location Pleural space Mediastinal space

Nasogastric tube

Stomach

Gastric tube (gastrostomy) Jejunal tube (jejunostomy)

Stomach

Duodenal tube

Duodenum

Penrose drain

Peritoneal space, small surgical space Surgical space

Jejunum

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Closed suction drain (eg, Jackson Pratt, Hemovac)

Clinical Indication Pneumothorax Hemothorax Pleural e usion Intestinal decompression, gastric eeding Prolonged enteral access, gastric decompression Prolonged postgastric eeding, gastric outlet obstruction, high aspiration risk Postgastric eeding, gastric outlet obstruction, high aspiration risk Used to maintain surgical tract or adequate drainage

Clinical Scenario Trauma, cardiac surgery, thoracic surgery, malignant e usion, empyema

Evacuate serous luid or blood, prevent seroma ormation, tissue apposition to improve wound healing, drain GI secretions

Mastectomy, ventral hernia repair, plastic surgery laps, gastrointestinal anastomoses, orthopedic surgery

The team that placed the tube should help the hospitalist determine the timing o the chest tube removal. I the patient has a pleural e usion, the chest tube can usually be removed when the output is less than 100 to 200 mL per day, and the lung is expanded. The tube should usually be taken o suction and placed on water seal (to rule out pneumothorax) prior to tube removal.

PRACTICE POINT Chest tubes

• • •

Contact the team who placed the chest tube i it needs adjustment or removal. Never advance a chest tube into the pleural space, due to the risk o introducing in ection. Do not clamp a tube when pneumothorax is suspected, due to the risk o precipitating a tension pneumothorax.

Small bowel obstruction, ileus, temporary dysphagia Prolonged mechanical ventilation, gastric outlet obstruction Prolonged mechanical ventilation, malignant gastric outlet obstruction, recurrent aspiration pneumonia Mechanical ventilation, dysphagia, acute aspiration risk

• Plastic surgery to prevent seroma ormation and to promote

tissue apposition • Cholecystectomy to drain bile • Inadvertent postoperative leakage ollowing a dif cult rectal anastomosis • Post pancreatic surgery Typically, closed suction drains will be le t in place until the drainage is less than 20 mL per day. These drains can be le t in or weeks i necessary and will o ten be removed upon the patient’s scheduled surgical ollow-up. Rare complications include erosion into surrounding tissues and inadvertent suturing o the drain in place such that re-exploration is required to remove it. I a closed suction drain becomes occluded, contact the team who placed the drain or urther recommendations on adjustment, replacement, or removal.

PRACTICE POINT Penrose and closed suction drains

PENROSE DRAINS Penrose drains are o ten used to drain uid or to keep a space open or drainage. Surgeons may anchor penrose drains to skin with sutures. Common indications include: • Ventral hernia repair • Debridement o in ected pancreatitis • Drainage o super cial abscess cavities

Penrose drains are simple, exible tubes open at both ends; in contrast to closed drains, they permit ingress as well as egress, acilitating colonization. CLOSED SUCTION DRAINS Closed suction drains with a plastic bulb attachment (ie, JacksonPratt, Blake, Hemovac) are used to collect uid rom a postoperative cavity. Common indications include: • Postmastectomy to drain subcutaneous uid • Abdominal surgery

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Always check with the surgeon who placed the drain be ore readjustment or removal. Noti y the surgeon i a patient has bloody drainage and/or a alling hematocrit.

NASOGASTRIC AND DUODENAL TUBES Nasogastric tubes (NGTs) are o ten used in the nonoperative management o small bowel obstruction or ileus. NGTs should be placed in the most dependent portion o the gastric lumen, and con rmed by chest or abdominal x-ray. NGTs are sump pumps and have a double lumen, which includes an air port to assure ow. The air port should be patent or optimal unctioning. The tube may be connected to continuous wall suction or intermittent suction, set to low (2 alcoholic drinks per day within 2 wk Preoperative trans usion o >4 units o packed red blood cells Chronic corticosteroid use Weight loss o >10% within 6 mo History o stroke ASA, American Society o Anesthesiologists.

C H A P T E R 5 1 P e r i o p e r a t i v e P u l m o n a r y R i s k A s s e s s m e n t a n d M a

Congestive heart ailure (CHF) is not only an obvious risk actor or perioperative cardiac complications but also a predictor o postoperative respiratory ailure. Although the cause o respiratory ailure may be CHF-related pulmonary edema, a history o heart ailure is nonetheless an independent risk actor or pulmonary complications that con ers a relative risk o approximately 6 in the geriatric population.

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Congestive heart failure

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at age 50 and is especially high in patients aged 70 years and older (adjusted odds ratio o 3). Recognition that age, even in the absence o other comorbidities, is an important source o pulmonary risk is critical as the population ages and more elderly patients undergo surgical procedures. The consequence o these observations is that even healthy older patients are at risk or postoperative pulmonary complications.

Large multivariate studies have also identi ed dependence on others or assistance with activities o daily living as a signi cant risk actor or postoperative pulmonary complications. The contribution o unctional dependence to perioperative pulmonary risk is greater than cigarette smoking and chronic lung disease. For patients with a completely dependent unctional status, the adjusted OR or respiratory complications is greater than 4, and or partial unctional dependence the adjusted OR is approximately 2.

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Functional status

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As the number o comorbid illnesses increases, so does the risk o perioperative complications. The American Society o Anesthesiologists (ASA) classi cation system is easy-to-use and predicts the risk o postoperative respiratory problems, as well as overall morbidity and mortality. Compared to ASA class I patients (no comorbidities), patients with an ASA class o II or greater have a nearly ve- old increase in the rate o postoperative pulmonary complications. The risk increases with each higher ASA class.

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Respiratory ailure

Medical comorbidities

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Pneumonia

Diagnostic Considerations • Potential cause o mild hypoxia • Generally not a cause o postoperative ever or moderate to severe hypoxia • Diagnostic criteria vary—utilize same as nosocomial pneumonia • O ten polymicrobial—common pathogens include Pseudomonas, Staphylococcus aureus, Streptococcus pneumoniae and enteric Gramnegative bacilli • Though aspiration o secretions is a likely contributor to development, anaerobic bacteria rarely cause postoperative pneumonia • Inability to wean o ventilator support within 48 h o surgery or unplanned reintubation • Typically, a combination o hypoxic and hypercapnic respiratory ailure • Diagnostic criteria and assessment same as in nonoperative population

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TABLE 51-1 Common Postoperative Pulmonary Complications

less than that rom most other patient-speci c actors including COPD. The adjusted odds ratio (OR) or pulmonary complications in smokers is 1.3, and the risk is greatest among active smokers and recent (2-3 h)

the surgical approach should be made by the surgeon based on other actors.

■ PROCEDURE-SPECIFIC RISK FACTORS Patient characteristics impact perioperative pulmonary risk signi cantly, but procedure-speci c actors are even greater predictors o postoperative pneumonia and respiratory ailure (Table 51-3). Unlike the majority o patient-speci c risk actors, some o these surgery-related actors may be modi able. Surgery type The type o surgery is the most important determinant o postsurgical pulmonary risk. As expected, intrathoracic procedures and surgeries in close proximity to the diaphragm carry the highest risk o postoperative pulmonary complications. Head and neck operations are high-risk procedures due in part to impairment o the upper airway. Restriction o diaphragmatic motion by pain rom abdominal procedures leads to reduced lung volumes, the precursor o pulmonary complications. Particularly high risks are esophageal and aortic surgeries.

Head and neck Thoracic, including esophageal Abdominal Abdominal aortic aneurysm repair Neurosurgical Vascular

PRACTICE POINT Strongest Predictors of Postoperative Pulmonary Complications The strongest predictors o postoperative pulmonary complications are: • Surgery type: A location anywhere rom the mouth to upper abdomen disrupts the airway and/or normal respiratory dynamics. • Advanced age: Beginning at age 50, perioperative pulmonary risk begins to increase and becomes particularly high in patients over the age o 70 years. • Obstructive sleep apnea: Known or presumed OSA, based on a positive screen, is an important risk actor. • Functional dependence: Reliance upon others or assistance with activities o daily living increases the risk o multiple complications, including postoperative respiratory problems.

Anesthetic technique Several studies have identi ed general endotracheal anesthesia (GETA) as an independent predictor o postoperative pulmonary complications. In some analyses, neuraxial blockade (spinal and epidural anesthesia), either alone or in combination with GETA, has been associated with lower rates o postoperative morbidity and mortality compared to GETA alone. However, randomized controlled trials (RCTs) have not consistently identi ed GETA as a risk actor. While these data suggest general anesthesia may contribute to pulmonary risk, selection o anesthetic technique is the primary responsibility o the anesthesiologist and is dependent on multiple other actors outside the purview o the hospitalist. The medical consultant should share his or her risk assessment with the anesthesiologist so they can incorporate this into anesthesia planning, but in general should de er the selection o anesthetic type to the anesthesiologist. Other risk factors Regardless o the surgical site or anesthetic technique, procedures per ormed on an emergent basis carry a higher risk o respiratory complications. Surgeries with duration greater than 2 to 3 hours are also associated with an increased risk or postoperative pneumonia and respiratory ailure. There is probably no di erence in risk between laparoscopic versus open surgeries; decisions regarding 338

■ DIAGNOSTIC STUDIES A thorough history and physical examination are the cornerstones o the preoperative evaluation. In most instances, diagnostic testing adds little to the risk assessment as established by clinical evaluation. Testing has a role when the risk is uncertain a ter history and physical examination. Chest radiography Chest radiography is part o many clinicians’ routine preoperative evaluation despite evidence that chest x-ray results rarely change perioperative management. Abnormalities on preoperative chest radiography are relatively common, occurring on 10% to 20% o x-rays. However, a minority o these ndings are unexpected based on the clinician’s physical assessment and history, and an even smaller number in uence perioperative care. Clinicians should reserve chest imaging or the same indications as in the nonoperative setting: evaluation o new or changed cardiopulmonary symptoms. As part o the American Board o Internal Medicine’s Choosing Wisely initiative, three di erent pro essional societies have speci cally recommended not obtaining preoperative chest radiographs in patients without clinical ndings suggestive o pulmonary abnormalities.

C H A P T E R 5 1 P e r i o p e r a t i v e P u l m o n a r y R i

Risk Score 44

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Risk Class Low Intermediate High

24 16 23 8 11 Postoperative Pulmonary Complications (%) 1.6-3.4 13-13.3 38-42.1

k

51-80 >80 Preoperative SpO2 (%) 91-95 2-3 >3 Emergency surgery Preoperative hemoglobin ≤10 g/dL

Risk Score 3 16 8 24 17 15

In recent years, the scienti c community has paid more attention to the importance o postoperative pulmonary complications. The result has been the generation o practical risk assessment tools. In 2006, the American College o Physicians developed clinical guidelines or perioperative pulmonary risk assessment and reduction or patients undergoing noncardiothoracic surgery. This systematic review provides a valuable resource or per orming an evidence-based preoperative evaluation. Several perioperative pulmonary risk prediction models have also been developed to assist clinical risk strati cation. Most o these are restricted to either speci c types o surgery or unique respiratory complications (eg, acute respiratory distress syndrome), but three recent models show promise or being airly generalizable. Using data rom the American College o Surgeons National Surgical Quality Improvement Program, Gupta and colleagues developed separate models or prediction o postoperative respiratory ailure and pneumonia. Predictive risk actors or postoperative respiratory ailure were: site o surgery, emergency surgery, ASA classi cation, sepsis and unctional status (ie, ability to per orm activities o daily living). The pneumonia risk model used the same variables except that age, COPD and smoking were included and emergent surgery was not. Both models were incorporated into risk calculators that are reely available online (www.surgicalriskcalculator.com). The Gupta postoperative pulmonary risk calculators per ormed very well in their initial study but have not been externally validated. In 2010, Canet and colleagues developed the ARISCAT index or predicting postsurgical pulmonary complications. This model uses seven predictive actors, each with a weighted score based on its risk contribution (Table 51-4). Tallying the score in this model the

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clinician can determine which o three di erent risk classes a patient its into. The ARISCAT index was originally derived and validated rom a geographically localized population but has subsequently been validated in a sample o patients rom across Europe. Although the above risk indices are help ul or estimating risk in the general population, they do not account or risks associated with obstructive sleep apnea. The ASA recommends screening all surgical patients or OSA. Several tools or this purpose are available, including the STOP-BANG, Berlin and Flemons surveys. The STOP-BANG questionnaire accurately identi es patients at risk or moderate to severe OSA and postoperative complications (Table 51-5). A score o 5 or higher (o eight possible points) increases the likelihood o moderate to severe OSA, as well as rates o perioperative complications.

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Diagnostic testing rarely adds value to perioperative pulmonary risk assessment in noncardiothoracic surgery. A thorough history and physical examination is suf cient in almost all cases.

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Used with permission rom Canet J, Gallart L, Gomar C, et al. Anesthesiology. 2010;113(6):1338-1350.

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Formal pulmonary unction testing has an established role in the preoperative evaluation o patients be ore lung resection, but its role in nonthoracic surgery is questionable. Analogous to ABG analysis, initial studies o preoperative spirometry suggested it was use ul or predicting postoperative morbidity, but later data comparing spirometry to history and physical examination showed no clear incremental bene t rom pulmonary unction testing. Further, no spirometric values are a prohibitory threshold or noncardiothoracic surgery. Indications or pulmonary unction testing are the same as in the general setting: evaluation o unexplained respiratory symptoms and characterization o lung disease when it is unclear i a patient’s air ow obstruction is optimally reduced.

Risk Factor Age (y)

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TABLE 51-4 ARISCAT Index for Predicting Postoperative Pulmonary Complications

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Early studies o preoperative arterial blood gas (ABG) analysis suggested that hypercarbia and hypoxemia predicted postoperative pulmonary complications. Subsequent reviews concluded that clinical assessment was equally accurate in predicting postsurgical respiratory problems. Taking into account that no arterial CO2 or O2 value is an absolute contraindication to surgery, clinicians should per orm ABG analysis only i the results will signi cantly in uence perioperative management (eg, excluding hypercarbia and respiratory acidosis in a patient with COPD and increased shortness o breath).

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TABLE 51-5 STOP-BANG Screening for Obstructive Sleep Apnea S

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Snoring: Do you snore loudly (loud enough to be heard through closed doors or your bed-partner elbows you or snoring at night)? Tired: Do you o ten eel tired, fatigued or sleepy during the daytime (such as alling asleep during driving)? Observed: Has anyone observed you stop breathing or choking/gasping during your sleep? Pressure: Do you have or are being treated or high blood pressure? BMI > 35 kg/m 2? Age older than 50 y? Neck size large? For male, shirt collar ≥17 in/43 cm; or emale, shirt collar ≥16 in/41 cm? Gender = male

Used with permission rom University Health Network.

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RISK REDUCTION STRATEGIES

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Many pulmonary risk actors are nonmodi able, but or patients with elevated perioperative risk several evidence-based risk reduction methods exist. Although some o these strategies are outside the scope o hospitalists, medical consultants should be aware o all potential risk reduction interventions. For all patients with increased pulmonary risk, special consideration should be given to the patient’s postoperative triage (home vs general hospital admission vs intensive care unit placement), and the hospitalist should incorporate the patient’s preoperative pulmonary risk assessment into postoperative care decision making. For instance, more aggressive work-up o postoperative ever or hypoxia may be initiated in the patient who was preoperatively assessed to be at increased risk or respiratory ailure or pneumonia.

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The role o smoking cessation in perioperative risk reduction remains an area o debate. Some studies have shown that preoperative smoking cessation decreases the risk o postsurgical respiratory complications, while others have demonstrated similar pulmonary morbidity between smokers and nonsmokers. An older study actually suggested an increase in postoperative pulmonary complications i smoking cessation occurred shortly be ore surgery. Recent meta-analyses o preoperative smoking cessation have identi ed no statistically signi cant increase in risk or patients who quit smoking less than 4 to 8 weeks be ore surgery. Patients who stop smoking more than 4 weeks prior to surgery have a signi cant decrease in postoperative pulmonary complications. Randomized controlled trials have con rmed that smoking cessation interventions started at least 1 month be ore surgery lower the incidence o overall complications. The greatest bene t occurs with durations o cessation o at least 8 weeks be ore surgery. Preoperative smoking cessation interventions (including the use o tobacco cessation pharmacotherapy) cause no harm, and increase rates o long-term abstinence. For any hospitalized surgical patient, clinicians should advise smoking cessation.

■ ANESTHETIC TECHNIQUES Anesthesia considerations are the responsibility o the anesthesiologist, but it is important or hospital medicine practitioners to understand potential risk reduction strategies related to anesthetic techniques. Previous studies have shown that avoidance o longacting neuromuscular blockade medications (pancuronium) can reduce the risk o postoperative pulmonary complications. This results rom less residual neuromuscular blockade and resultant hypoventilation a ter surgery. Data supporting the use o neuraxial (epidural or spinal) anesthesia as a risk reduction modality has been mixed as well. However, a 2012 Cochrane review determined that neuraxial (spinal or epidural) anesthesia either alone or when added to general anesthesia signi cantly reduced the risk o postoperative pneumonia.

■ ANALGESIC TECHNIQUES Sedating analgesics (including opioids and some adjunctive agents) increase the risk o hypoventilation which can lead to atelectasis and other respiratory complications. Thus, limitation o systemic opioids through epidural or regional analgesia or patient-controlled analgesia (PCA) o ers the potential or pulmonary risk reduction. Neuraxial analgesia o ers more risk reduction than PCA. In addition to less potential or hypoventilation, these strategies reduce postoperative pain, and increase the ability to take deep breaths and increase lung volumes a ter surgery. Meta-analyses o abdominal aortic and cardiac surgery patients have demonstrated reduced postsurgical 340

respiratory problems with the use o thoracic epidural analgesia. However, evidence o bene t rom other regional analgesia is scant. Administration o intravenous opioids through PCA reduces the risk o pulmonary complications when compared to intermittent intravenous administration on a PRN basis.

■ LUNG EXPANSION TECHNIQUES The largest body o evidence or a perioperative pulmonary risk reduction strategy is or lung expansion techniques. Incentive spirometry, intermittent positive pressure breathing, deep breathing exercises and continuous positive airway pressure each reduce the risk o postoperative pulmonary complications. None o these strategies has been shown to be superior to another. Given the minimal risk associated with these techniques, the American College o Physicians recommends that incentive spirometry or deep breathing exercises be used or all patients at risk or pulmonary complications. Furthermore, a number o studies have demonstrated the value o lung expansion techniques or cardiopulmonary conditioning therapy started 1 to 2 weeks prior to surgery. This strategy reduces rates o pneumonia and all pulmonary complications by approximately one-hal . Preoperative initiation o lung expansion or cardiopulmonary physiotherapy should be considered or patients with elevated pulmonary risk.

■ SELECTIVE NASOGASTRIC DECOMPRESSION The American College o Physicians also recommends use o nasogastric tubes only as needed or postoperative nausea or vomiting, oral intake intolerance or symptomatic abdominal distention. This recommendation results rom observations that routine, rather than selective, nasogastric decompression ollowing abdominal surgery led to increased rates o pneumonia and atelectasis.

■ LUNG-PROTECTIVE VENTILATION A growing body o evidence also supports the use o lung-protective ventilation (lower tidal volume, higher levels o positive end-expiratory pressure [PEEP] and lung recruitment maneuvers) in patients who require perioperative mechanical ventilation. This approach has long been utilized in patients with acute respiratory distress syndrome to reduce ventilator-associated lung injury. More recently, studies and meta-analyses have also shown reduced postoperative pulmonary complications in patients ventilated with tidal volumes o 6 to 8 cc/kg and PEEP o 5 to 10 cm o water pressure (cwp). Data rom a 2014 randomized controlled trial indicates that use o lower tidal volume (8 cc/kg) with PEEP levels more than 10 cwp results in an increased risk o hypotension. There ore, multiple actors in uence the selection o an optimal postoperative ventilation strategy (eg, risk o hypotension).

■ OBSTRUCTIVE SLEEP APNEA MANAGEMENT As the impact o OSA on perioperative risk is now well established, experts have developed a number o strategies to reduce the risk o sleep apnea-related postoperative complications. Most o these interventions were not derived rom RCTs, but prospective studies o patients screened as high risk or OSA provide some evidence o their ef cacy. High-risk patients in whom such OSA-targeted interventions were employed have complication rates similar to patients at low risk or OSA. The 2014 ASA practice advisory or perioperative OSA management suggests several strategies or mitigating sleep apnea-related risks (Table 51-6). For patients likely to have severe OSA, empiric use o positive airway pressure (PAP) ventilation is recommended i signs o severe hypoxia or airway obstruction are evident. At least one recent RCT demonstrated no reduction in postoperative pulmonary complications rom empiric PAP initiation postoperatively (ie, without signs or symptoms o hypoxemia or

PRACTICE POINT Why Preoperative Pulmonary Evaluation Matters Pulmonary evaluation has been traditionally undervalued or a number o reasons: • Most o the risk actors or postoperative pulmonary complications are nonmodi able. • Many o the available risk reduction strategies are either beyond the responsibility o the primary care physician/ hospitalist (choice o anesthesia and surgical approach) or routinely utilized (incentive spirometry and deep breathing exercises).

C H A P T E R 5 1 P e r i o p e r a t i v e P u l m o n a r y

Gupta H, et al. Development and validation o a risk calculator or predicting postoperative pneumonia. Mayo Clin Proc. 2013;88:1241.

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Gupta H, et al. Development and validation o a risk calculator predicting postoperative respiratory ailure. Chest. 2011;140:1207.

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Chung F, et al. High STOP-Bang score indicates a high probability o obstructive sleep apnea. Br J Anaesth. 2012;108:768.

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Postoperative pulmonary complications are an under-recognized source o signi cant surgical morbidity and mortality. Estimation o pulmonary risk is an essential part o the preoperative evaluation and includes assessment o both patient- and procedure-related risk actors. Most risk actors are not modi able, but the preoperative pulmonary evaluation provides an accurate estimation o risk or patients and physicians that improves in ormed decision making. Moreover, identi cation o high-risk patients can heighten postoperative vigilance or respiratory ailure and pneumonia and lead to the use o those strategies proven to reduce risk.

American Society o Anesthesiologists Task Force on Perioperative Management o patients with obstructive sleep apnea. Practice guidelines or the perioperative management o patients with obstructive sleep apnea: an updated report by the American Society o Anesthesiologists Task Force on Perioperative Management o patients with obstructive sleep apnea. Anesthesiology. 2014;120:268.

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airway obstruction). When possible, surgery should be delayed or preoperative evaluation and management o OSA or patients likely to have severe sleep apnea and are undergoing major surgery. Retrospective studies suggest that patients who are ormally diagnosed and started on appropriate PAP therapy preoperatively have lower rates o postoperative complications compared to those who were diagnosed and treated a ter surgery.

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ASA, American Society o Anesthesiologists; NSAIDs, nonsteroidal antiin lammatory drugs; PAP, positive airway pressure.

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Elevate head o bed (unless contraindicated by surgical requirements) Continuous pulse oximetry (with centralized monitoring) Use adjunctive analgesics (eg, NSAIDs) to reduce systemic opioid needs Minimize use o nonopioid sedatives PAP therapy Previously on home PAP: have patient use home PAP device whenever sleeping No previous PAP: initiate PAP or requent or severe airway obstruction or hypoxemia

However, identi cation o patients at increased pulmonary risk remains critical or the ollowing reasons: • Communication o increased pulmonary risk to the anesthesiologist and surgical team prompts consideration o risk reduction strategies under their control. • Modi cation o the postoperative care unit team’s triage decisions. For example, a ter a surgery that would usually be done as an outpatient, a high-risk patient may be admitted or extended observation. • Heightened postoperative vigilance or respiratory problems. Speci c examples o e ects on management include: Lower threshold or initiating workup or pneumonia in setting o postoperative ever (which might otherwise be attributed to benign causes) Admission to unit specializing in respiratory care or mobilization o respiratory therapy resources beyond traditional scope Lower threshold or treatment o postoperative pneumonia when chest radiographs are equivocal

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TABLE 51-6 ASA Recommendations for Postoperative Management of Patients with Known or Suspected Sleep Apnea

Mazo V, et al. Prospective external validation o a predictive score or postoperative pulmonary complications. Anesthesiology. 2014;121:219. Minai OA, et al. Perioperative risk and management in patients with pulmonary hypertension. Chest. 2013;144:329. Qaseem A, et al. Risk assessment or and strategies to reduce perioperative pulmonary complications or patients undergoing noncardiothoracic surgery: a guideline rom the American College o Physicians. Ann Intern Med. 2006;144:581. Wong J, et al. Short-term preoperative smoking cessation and postoperative complications: a systematic review and metaanalysis. Can J Anaesth. 2012;59:268.

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Perioperative Risk Assessment and Management of the Diabetic Patient Katherine Lewis, MD Kathie L. Hermayer, MD

INTRODUCTION About 21 million adults have diabetes in the United States, and 5.5 million hospital discharges include diabetes as one o the listed diagnoses. Annual inpatient health care costs directly related to diabetes were estimated at $76 billion in 2012. People with diabetes have a higher li etime probability o requiring surgery compared to the general population due to increased cardiovascular, ophthalmic, renal, and neuropathic complications rom their disease. Diabetes mellitus itsel may complicate surgical wound healing and recovery. Surgical site in ections may be twice as high in patients with diabetes, potentially rom small vessel disease impairing oxygen and nutrient delivery to tissues, impaired leukocyte and monocyte unction due to hyperglycemia, and decreased release o neuropeptides in those with peripheral neuropathy. Patients with diabetes also have higher postoperative in-hospital mortality compared to those without diabetes. Patients with higher postoperative blood sugars a ter coronary bypass surgery have an increased rate o complications. Surgery and anesthesia provoke release o counter-regulatory hormones, which cause hyperglycemia and increased catabolism. Care or the surgical patient with diabetes should ocus on avoidance o marked hyperglycemia, which can alter wound healing and disrupt uid balance, while also avoiding hypoglycemia, which can cause cardiac stress. Perioperative evaluation or patients with diabetes allows or the development o an individualized plan to reduce perioperative complications and to determine a sa e and e ective diabetes discharge plan. PREOPERATIVE EVALUATION A thorough history remains a key component in the preoperative evaluation o the patient with diabetes. A history o comorbidities and complications associated with diabetes may provide additional insight into surgical risk, and there ore perioperative management. For example, elective surgery should be delayed in patients with diabetes a ter a recent cardiac event (see Chapter 50: Preoperative Cardiac Risk Assessment and Perioperative Management). Patients with concomitant renal disease need to be monitored care ully, with precautions to avoid contrast materials and other nephrotoxic agents. Diabetic autonomic neuropathy may predispose patients to perioperative hypotension. Gastroparesis with impaired gastric emptying may predispose patients to aspiration during intubation and extubation. Clarif cation o the patient’s home diabetes regimen and assessment o their home glycemic control and adherence will help guide perioperative management. Ideally, patients will have good glycemic control prior to undergoing elective surgery, but this will not always be possible. Some experts advocate delaying elective surgery i the patients HbA1C is >8.5%, but there is no good literature to support or negate this practice. In addition, the management plan should take into consideration the patients’ typical diet and activity, which may change drastically in the perioperative period. The type and duration o surgery is also important to consider, as longer surgeries and recovery times (including ICU admission or prolonged NPO status) will a ect the perioperative glycemic management plan. Specif c physical exam components or patients with diabetes should include inspection o injection sites or insulin pump in usion sites (i applicable) or evidence o lipohypertrophy, which may a ect insulin absorption. Evaluation or signs and symptoms o

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For patients on insulin, basal insulin in many cases can be given at the regular dose or slightly reduced doses or short procedures. In patients with Type 1 diabetes, basal insulin should not be held due to the risk o diabetic ketoacidosis. A reduction in basal insulin may be needed i the patient gives a history o requent snacking in

C H A P T E R 5 2 P e r i o p e r a t i v e R i s k A s s e s s m e n t a n d M a n a g e m e n t o t h e D i a b e t i c P

During surgery, glucose should be monitored hourly or procedures lasting >60 minutes. Glycemic targets or noncritically ill patients on insulin should be 40) Thrombocytopenia (platelets < 75 × 109/L)

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TABLE 56-2 Contraindications to VTE Prophylaxis with Anticoagulants

o u s T h r o m b o e m b o l i s m ( V T E ) P r o p h y l a x i s o r N o n c

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Pharmacologic prophylaxis should be the thromboprophylaxis strategy o choice in nonorthopedic surgery. Mechanical methods o prophylaxis, which include graduated compression stockings and intermittent pneumatic compression devices, are a sa e option in patients with an increased bleeding risk. However, they are in erior to pharmacologic prophylaxis, and are insuf cient protection against VTE in patients at high risk o thrombosis.

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Laparoscopic surgery is becoming an increasingly popular alternative to conventional open surgical procedures, due to decreased tissue trauma and aster recovery times. However, there are some unique eatures o laparoscopic surgery that increase thrombosis risk, including longer intraoperative time, the reverse Trendelenburg position, and pneumoperitoneum (which creates venous stasis in the lower extremities). Nevertheless, rates o symptomatic VTE ollowing laparoscopic surgery are lower than in general surgery, less than 0.5% in most series. Rates o asymptomatic VTE are thought to be lower than 1%. For this reason, routine VTE prophylaxis is not recommended in laparoscopic surgery. Bariatric surgery, which includes Roux-en-Ygastric bypass, gastric banding, vertical-banded gastroplasty, and biliopancreatic diversion, is also a growing eld. More than 100,000 bariatric surgeries or morbid obesity are per ormed in the United States every year. Obesity is a known risk actor or VTE and puts bariatric surgery patients in a unique risk group. Rates o symptomatic VTE vary depending on the study quoted, anywhere rom 0.8% to 2.4%. However, there is still insuf cient high-quality evidence to make clear recommendations regarding VTE prophylaxis in bariatric surgery. Early ambulation and mechanical prophylaxis (either IPC or GCS) are widely accepted components o postoperative care in bariatric surgery patients. The American College o Chest Physicians’ most recent guidelines also recommend LMWH, LDUH, or ondaparinux be routinely used. Consultation with a pharmacist is important, as patients who are obese who may require higher drug doses.

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PRACTICE POINT

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Physicians have a number o options available when choosing the type o VTE prophylaxis in nonorthopedic surgery. Mechanical methods o prophylaxis, which include graduated compression stockings and intermittent pneumatic compression devices, are a sa e option in patients with an increased bleeding risk (Table 56-2). However, they are in erior to pharmacologic prophylaxis and are insuf cient protection against VTE in patients at high risk o thrombosis. All patients with an increased risk or bleeding should be reassessed regularly so pharmacologic prophylaxis can be started when the bleeding risk decreases to an acceptable level. Pharmacologic prophylaxis should be the thromboprophylaxis strategy o choice in nonorthopedic surgery. Re er to Table 56-3 or the recommended dose regimens. Note that these doses may be inadequate in the bariatric surgery population, and that LMWH dosing in obese patients remains controversial. Two studies have shown that enoxaparin 40 mg every 12 hours subcutaneously ( or bariatric surgery patients with BMI ≤50 kg/m2) or 60 mg every 12 hours ( or BMI >50 kg/m2) appears to be an e ective VTE prophylaxis strategy.

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Patients undergoing major neurosurgery are at a moderate risk or VTE, with rates o proximal DVT as high as 5% postoperatively. Those with malignant brain tumors are at particularly high risk. One prospective study o more than 250 patients with gliomas showed that 31% had symptomatic, venographically con rmed DVT within 5 weeks o their surgery. However, a major barrier to optimal VTE prophylaxis in neurosurgery patients is their risk o bleeding. Intracranial bleeding can have devastating clinical consequences, and or this reason, preoperative and early postoperative pharmacologic prophylaxis should be used with caution in craniotomy patients. Rates o intracranial hemorrhage appear to double when postoperative LMWH is compared to mechanical or no VTE prophylaxis (approximately 2%-6% vs 1%-3%). Most o these bleeds occur within the rst 2 days a ter surgery. A reasonable approach that balances the risks o bleeding and thrombosis is to start mechanical VTE prophylaxis with properly tted IPC at the time o neurosurgery. Perioperative use o IPC is highly e ective, reducing the risk o VTE by more than two-thirds. I a care ul clinical assessment is stable and postoperative CT scan does not show bleeding at 24 to 48 hours, LMWH or LDUH can be added to urther protect the patient rom VTE. There is no evidence or extended prophylaxis in neurosurgery patients.

WHAT PHARMACOLOGIC AND NONPHARMACOLOGIC STRATEGIES SHOULD BE USED FOR VTE PROPHYLAXIS?

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to all cardiac surgery patients; however, in CABG patients who do not receive ull-dose therapeutic anticoagulation postoperatively most physicians elect to use prophylactic-dose heparin or bilateral mechanical VTE prophylaxis (i the patient has not had saphenous vein gra ting). Because the risk o HIT is high in cardiac surgery, LMWH is pre erred over LDUH. Attention must, however, be paid to bleeding risk; this risk goes up with concomitant antiplatelet use, older age, renal insuf ciency, and longer bypass time. I bleeding is a concern, mechanical VTE prophylaxis is pre erred over pharmacologic VTE prophylaxis.

Other studies have tried to address this issue by using anti-Xa levels as a primary outcome instead o clinical events. Prospective nonrandomized studies have questioned the validity o a “maximum LMWH dose” by showing that increasing the total daily dose

TABLE 56-3 Pharmacologic Prophylaxis Options in Nonorthopedic Surgery Fondaparinux (Arixtra) 2.5 mg SC once daily Dalteparin (Fragmin) 2500 units or 5000 units SC once daily Enoxaparin (Lovenox) 40 mg SC once daily or 30 mg SC every 12 h Nadroparin (Fraxiparine) 1900-3800 anti-Xa units SC once daily Tinzaparin (Innohep) 3500 or 4500 anti-Xa units SC once daily Heparin 5000 units SC every 12 h or every 8 h

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o LMWH by 50% or patients with a BMI >50 kg/m 2 can e ectively increase patients’ anti-Xa levels to the target prophylactic range (0.2-0.4 IU/mL). However, these studies were not all suf ciently powered to detect clinically relevant bleeding. Higher doses o anticoagulant do seem necessary to achieve an appropriate level o prophylaxis or obese patients, though physicians must be cautious o bleeding complications as they increase LMWH dosing. Anti-Xa levels, though not a surrogate marker or bleeding risk, can provide a use ul adjunct to close clinical monitoring.

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There is no evidence that patients undergoing nonorthopedic surgery bene t rom routine DVT screening using Doppler ultrasound or venography. This strategy may pick up asymptomatic venous thrombosis in a small number o patients, but does not appear to reduce the rates o clinically signi cant events. There is also no robust evidence that VTE prophylaxis should be extended a ter hospital discharge. Patients at particularly high risk o thrombosis (eg, major abdominal or pelvic surgery, cancer surgery, prolonged immobility, and multiple other risk actors), may be candidates or extended prophylaxis or our additional weeks, generally with parenteral anticoagulants. The hospitalist can acilitate this transition by arranging nursing care at home, instructing the patient (or a caregiver) on injection technique and sa e disposal o used needles, and clari ying who to call i bleeding develops. All patients should be educated about the signs and symptoms o VTE during their hospital stay and at the time o discharge.

■ QUALITY IMPROVEMENT INITIATIVES TO OPTIMIZE VTE PROPHYLAXIS VTE prophylaxis in nonorthopedic surgery patients is a critical public health issue. In 2009, the US Surgeon General cited VTE as one o the most preventable hospital-acquired illnesses, and issued a call to action to optimize its prevention. Though VTE prophylaxis in nonorthopedic surgery is based on scienti c evidence, the quality and number o trials is limited compared to the orthopedic surgery population. There is also signi cant room or improvement in compliance rates with the American College o Chest Physicians’ guidelines or in-hospital VTE prophylaxis. Concerted system-wide and local e orts must be made to increase the appropriate use o VTE prophylaxis in nonorthopedic surgery.

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SUGGESTED READINGS Agnelli G, Bergqvist D, Cohen AT, et al. Randomized clinical trial o postoperative ondaparinux versus perioperative dalteparin or prevention o venous thromboembolism in high-risk abdominal surgery. Br J Surg. 2005;92:1212-1220. Bergqvist D, Agnelli G, Cohen AT, et al. Duration o prophylaxis against venous thromboembolism with enoxaparin a ter surgery or cancer. N Engl J Med. 2002;346:975-980. Borkgren-Okonek MJ, Hart RW, Pantano JE, et al. Enoxaparin thromboprophylaxis in gastric bypass patients: Extended duration, dose strati cation, and anti actor Xa activity. Surg Obes Relat Dis. 2008;4(5):625. Caprini JA. Risk assessment as a guide or the prevention o the many aces o venous thromboembolism. Am J Surg. 2010;199:S3. Clagett GP, Reisch JS. Prevention o venous thromboembolism in general surgical patient: results o meta-analysis. Ann Surg. 1988;208:227-240. Collins R, Scrimgeour A, Yusu S. Reduction in atal pulmonary embolism and venous thrombosis by perioperative administration o subcutaneous heparin: Overview o results o randomized trials in general, orthopedic, and urologic surgery. N Engl J Med. 1988;318:1162-1173. Goldhaber SZ, Schoep UJ. Pulmonary embolism a ter coronary artery bypass gra ting. Circulation. 2004;109:2712-2715. Gould MK, Garcia DA, Wren SM, et al. Prevention of VTE in nonorthopedic surgical patients: Antithrombotic therapy and prevention o thrombosis, 9th ed. American College o Chest Physicians evidencebased clinical practical guidelines. Chest. 2012;141:e227S. Mismetti P, Laporte S, Darmon JY, Buchmüller A, Decousus H. Meta-analysis o low molecular weight heparin in the prevention o venous thromboembolism in general surgery. Br J Surg. 2001;88(7):913-930. Scholten DJ, Hoedema RM, Scholten SE. A comparison o two di erent prophylactic dose regimens o low molecular weight heparin in bariatric surgery. Obes Surg. 2002;12(1):19. Simone EP, Madan AK, Tichansky DS, et al. Comparison o two lowmolecular-weight heparin dosing regimens or patients undergoing laparoscopic bariatric surgery. Surg Endosc. 2008;22(11): 2392-2395.

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Postoperative Blood Transfusion Olga S. Chajewski, MD Jerry E. Squires, MD, PhD

INTRODUCTION Over 13.8 million units o red blood cells are trans used to over 5 million patients in the United States in 2011; blood trans usion is one o the most common procedure codes recorded at discharge or hospitalized patients. It is estimated that 60% to 70% o these trans usions occur in relation to surgical procedures. For over 40 years it was generally assumed that patients bene tted rom trans usions whenever the hemoglobin ell below 10 g/dL or i the hematocrit ell below 30% (the so-called “10/30 rule”). Controversy remains regarding the appropriate selection o patients requiring trans usion, as well as the recognition and management o adverse trans usion reactions. POSTOPERATIVE ANEMIA Trans usion in the postoperative period generally occurs due to anemia. The prevalence o postoperative anemia is di cult to assess accurately, but it is undoubtedly common, particularly in critically ill patients. Hemoglobin concentrations on admission to the intensive care unit (ICU) are on average 11.0 to 11.3 g/dL in two large studies, with overall trans usion prevalence rates o 37% to 44%. Postoperative anemia can result rom several actors, but acute and chronic blood loss is most requently cited. While intraoperative or traumatic blood loss is generally replaced during the surgical procedure, a signi cant number o patients still leave surgery with some degree o anemia. Patients admitted to the ICU ollowing surgery on average have hemoglobin levels ranging rom 10.8 to 11.5 g/dL. Perhaps more insidious is the chronic blood loss that can occur during the postoperative period itsel . Causes or this include ongoing bleeding rom the surgical site (eg, chest tube drainage) and repeated blood collections or laboratory testing. It has been suggested that 40 to 60 mL o blood is routinely collected rom ICU patients daily. While this daily blood loss may seem minimal, it is aggravated by the decreased production o erythropoietin (EPO), resistance to the e ects o EPO, and an inability to utilize iron in red cell production, all o which have been documented in the postoperative period. In patients who display symptoms o anemia in the postoperative period, there are limited alternatives to trans usion. EPO and iron therapy are o ten ine ective in the postoperative period and are o little use in the patient with an acute need or blood.

PRACTICE POINT Arguments in avor o conservative management o postoperative anemia without the use o blood products include:

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Risks associated with blood trans usion. Accumulating evidence that trans usion can negative impact patient outcomes.

Steps that may be taken include:

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Minimize blood draws to tests that would inf uence management. Assess the clinical need or trans usion in each individual patient and only trans using patients likely to bene t rom trans usion (ie, generally those with a hemoglobin 50 kg/m 2 should receive 22 to 25 kcal/kg/d using IBW. In addition to a caloric prescription, providers should determine their patients’ protein goals. Generally, hospitalized patients require between 1.2 and 1.5 g/kg/d, with burn patients requiring up to 2.0 g/kg/d. In critically ill obese patients, up to 2.5 g/kg/d (IBW) is recommended.

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■ ROUTE OF FEEDING Figure 58 1 Percent change in metabolic rate due to injury.

• The Mi in-St. Jeor equation may be more accurate than

the HBE or determining caloric needs (when compared to indirect calorimetry). This equation is recommended for obese noncritically ill patients (although precision goes down with increasing obesity). • Penn State equation is the Mi in-St. Jeor equation modi ed with age, body temperature, and minute ventilation or eucaloric eeding. This equation is recommended for obese critically ill patients. No equations actor in the increased caloric expenditure related to disease. Hence, once the BMR is determined, an estimate o the additional caloric expenditure rom activity and metabolic stress ( rom disease or acute illness) is actored in to determine the overall daily caloric requirement. Stress actors can range rom 10% in routine patients to 100% in severe burn patients (Figure 58-1).

The next component o the nutrition prescription is determining the route o eeding (Figure 58-3). Oral nutrition is pre erred. Specialized nutritional support must be considered when patients cannot sa ely or adequately meet their nutrient requirements through oral diet alone. ENTERAL NUTRITION For the purpose o this discussion, enteral nutrition will re er to eeding o patients via enteric tubes placed in the stomach or small bowel. The old adage “i the gut works, use it” guides decision making or specialized nutritional support. Provision o nutrients into the GI tract preserves structural and unctional integrity and maintains gut-associated lymphoid tissue. Relative and absolute contraindications to enteral eeding include major GI hemorrhage, peritonitis, severe ileus, bowel obstruction or stulae distal to enteral access site, intestinal ischemia, and malabsorptive disorders with high-volume diarrhea (eg, short bowel syndrome, radiation enteritis, gra t vs host disease o the GI tract).

Harris Be ne dic t Equatio n Me n: [13.75 x we ight (kg)] + [5.00 x he ight (cm)] – [6.78 x a ge (y)] + 66.5 Wome n: [9.56 x we ight (kg)] + [1.85 x he ight (cm)] – [4.68 x a ge (y)] + 655.1 Mifflin-S t. Je o r Equatio n Me n: (9.99 x we ight) + (6.25 x he ight) – (4.92 x a ge ) + 5 Wome n: (9.99 x we ight) + (6.25 x he ight) – (4.92 x a ge ) – 161 Example : A 45-ye a r-old ma n pre s e nts a dive rticula r a bs ce s s with ile us. He is 6 ft ta ll (182.9 cm) a nd 176 lbs (80 kg). BMR (us ing Mifflin-S t. Je o r) = [9.99 x 80] + [6.25 x 182.9] – [4.92 x 45] + 5 = 1726 Calo rie Re quire me nt = 1726 (BMR) x 1.25 (ie , 25% ac tivity fac to r) x 1.10 (ie ,10% s tre s s fac to r) = 2473 c alo rie s /d Figure 58 2 Equations for determining basal metabolic rate. 379

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Cons ide r nutritiona l s upport if a ny of the following conditions a re pre s e nt: • Pa tie nt ha s be e n without nutrition for ≥7-10 days. • Expe cte d dura tion of illne s s >10 days. • Pa tie nt is ma lnouris he d (we ight los s > 10% of us ua l we ight).

M

Initia te nutritiona l s upport only if tis s ue pe rfus ion is a de qua te a nd p O 2 , p CO 2 , e le ctrolyte s , a nd a cid-ba s e ba la nce a re ne a r norma l

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Is GI output ≥ 600 mL/24 h, ma s s ive GI he morrha ge , prolonge d ile us, or othe r contra indica tion to e nte ra l fe e ding? Ye s

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Adminis te r pa re nte ra l nutrition

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Initia te e nte ra l fe e dings Ente ra l fe e ding tole ra te d

Ente ra l fe e ding not tole ra te d

Initia te TP N

Initia te P P N

Re a s s e s s ne e d for PN Figure 58 3 Determining route of nutritional support.

■ ENTERAL ACCESS

■ MONITORING ENTERAL FEEDING TOLERANCE

The physician must determine the most appropriate access route based on two major actors: (1) whether the patient requires shortor long-term eeding, and (2) whether the gastric status is normal. Re er to Chapter 45 (Surgical Tubes and Drains) on inserting and maintaining enteral tubes.

Feedings are typically started at a low rate, and gradually advanced to the in usion goal over a period o 24 to 48 hours. Patients are evaluated or other symptoms such as nausea, vomiting, diarrhea, abdominal pain, and bloating. Diarrhea commonly occurs due to gastrointestinal pathogens, bowel edema or in ammation, malabsorptive disorders, and medications (Figure 58-4). Also see Chapter 82 (Diarrhea) or more on the assessment and management o hospitalized patients with diarrhea. I signs and symptoms o intolerance develop, the eedings are held until resolution. Persistent intolerance requires an alternative plan. Patients receiving gastric eedings should be considered or postpyloric eeding as this may improve most symptoms o intolerance with the exception o diarrhea. Checking gastric residuals has traditionally been the hallmark or monitoring tube eeding tolerance and avoiding tube- eed-associated aspiration. However, several well-designed studies have ailed to demonstrate a signi cant link to gastric residual volume (GRV) and aspiration risk. Routine monitoring o gastric residuals interrupts tube eeding with questionable proven bene t.

■ ENTERAL FORMULAS Standard and specialized enteral ormulas can be used to provide nutrition. Since all o these ormulas have xed macronutrient content, it may not be possible to deliver su cient protein without over eeding calories. Hence, one usually delivers the eedings at a rate to provide appropriate calories and then supplements protein with a protein modular. Table 58-1 describes typical enteric ormulas. Specialty ormulas or a variety o disease states such as pulmonary, renal, and liver dys unction and diabetes should be selected with caution due to increased cost and low bene t to risk pro les.

TABLE 58-1 Typical Enteric Formulas

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Type Polymeric (1.0, 1.2, 1.5, and 2.0 cal/mL)

Composition Intact protein, ats, carbohydrates

Elemental or Semi-elemental

Peptide-based amino-acids or di- or tri-peptides and simple sugars

Immune enhancing diets

Forti ied with arginine, glutamine, omega-3 atty acids and/or antioxidants

Indications To meet daily requirements: or most patients 1-1.5 L/d Concentrated eeding best i patient is volume restricted Maximizes absorption in patients with malabsorption disorders May reduce in ection risk in surgical patients

Side Effects Concentrated eeding may cause diarrhea and may require ree water supplementation May cause diarrhea

Unclear bene it in medical patients

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Dia rrhe a > 600 cc/d

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• Re duce tube fe e ding ra te • Provide s oluble fibe r

N u t r i t i o n a n d M e t a

Offe nding me dica tions, e g • Antibiotics • S orbitol-conta ining me dica tions • Unindica te d la ctulos e /la xa tive s • Ma gne s ium-conta ining a nta cids • Pota s s ium or phos phorus s upple me nts • Antine opla s tics

b

Dis e a s e /infla mma tion, e g • Pa ncre a tic ins ufficie ncy • Bile s a lt ma la bs orption • S hort bowe l syndrome • Infla mma tory bowe l dis e a s e • Bowe l wa ll e de ma

Dia rrhe a improve d 600 cc/d

Antimotility me dica tions Immodium (lope ra mide HCl) Lomotil (diphe noxyla te HCl a nd a tropine s ulfa te ) Code ine De odorize d tincture of opium

Dia rrhe a improve d 600 cc/d Cha nge to pe ptide -ba s e d or e le me nta l tube fe e ding formula

Dia rrhe a improve d 600 cc/d S top e nte ra l fe e dings, cons ide r TP N

Figure 58 4 Management of diarrhea in tube-fed patients.

PRACTICE POINT The American Society or Parenteral and Enteral Nutrition (A.S.P.E.N.) recommends monitoring o gastric residual volume (GRV) or the rst 48 hours o enteral nutrition initiation. • I the GRVis greater than 250 mL on two residual checks, the physician should consider a motility agent such as metoclopromide or erythromycin. • I the gastric residual is greater than 500 mL, the eedings should be held and the patient evaluated by a physician or abdominal distention, glycemic control, adequacy o motility agents i not already ordered, or consideration o small bowel eeding access.

PARENTERAL NUTRITION Patients who cannot tolerate EN should be considered or parenteral nutrition (PN). PN is associated with higher rates o in ectious and metabolic complications such as volume overload, hyperglycemia, and electrolyte abnormalities compared to EN. The risk o nutritionally related complication rates increases beyond 10 to 14 days o inadequate enteral eeding in well-nourished individuals. The decision o when to initiate TPN depends on the nutritional status o the patient, the acute illness, the patient’s prognosis, and the estimated duration o inadequate enteral eeding. ASPEN recommendations suggest around 7 days as an appropriate starting point or PN. PN is only justi ed i the need is anticipated or a minimum o 5 days. 381

Indications or PN include, but are not limited to:

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• Severe malabsorptive disorders (short bowel syndrome, gra t

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• • • •

vs host disease o the GI tract, radiation enteritis, in ammatory bowel disease) High-output enterocutaneous stulae i distal eeding access is not easible Pancreatitis with enteral eeding intolerance Bowel obstruction Uncontrolled anastomotic leak ollowing GI surgery Prolonged postoperative ileus

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■ PARENTERAL NUTRITION PRESCRIPTION

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AND MONITORING

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PN solutions contain carbohydrate in the orm o dextrose, protein as crystalline amino acids, and lipids rom polyunsaturated longchain triglycerides such as soybean oil or a sa ower/soybean oil mixture. Vitamins, electrolytes, and trace elements are added to the ormulation as needed. Electrolytes and other additives (eg, medications) must be added at the appropriate concentrations to avoid “cracking” o lipid-containing PN. I cracking occurs, precipitates orm in the solution, and the lipid emulsion separates into layers, making it unsa e or administration. Physicians must care ully monitor patients or metabolic changes such as hyperglycemia or re eeding syndrome upon initiation o PN. Hyperglycemia may increase in ectious complications, hospital length o stay, and cost. Re eeding syndrome is characterized by electrolyte abnormalities that occur during the reinstitution o carbohydrate calories to a starved patient. Serum phosphate, magnesium, and potassium depletion may develop and precipitate potentially li e-threatening cardiac arrhythmias or neuromuscular complications. See Chapter 226 (Eating Disorders or more on the re eeding syndrome). PN prescriptions typically provide rom 1 to 3 liters o uid per day depending on the physician’s assessment o maintenance uid requirements. A general rule o thumb is 30 mL/kg. Carbohydrates generally make up about 50% to 60% o the caloric prescription, at 3.4 calories/g o dextrose. Protein generally provides about 15% to 25% o the calories at 4.0 calories/g o amino acid. The current US Food and Drug Administration (FDA)-approved lipid emulsions are primarily made up o omega-6-rich oils, which have been shown to be proin ammatory and potentially immunosuppressive. Hence, lipid provision should be limited to 20% to 25% o calories (at 10 calories/g o IV lipid). Novel IV lipids made up o olive oils or sh oil are available in other countries, and are currently under consideration by the FDA. It is advisable to start with a lower volume and concentration o dextrose when initiating PN to avoid metabolic complications. One liter o a 10% dextrose solution is a good starting point. Subsequently the volume, and dextrose, lipid, and protein concentrations are increased as needed in the metabolically stable patient to the eventual goal caloric and uid provision (Figure 58-5). Blood sugar levels should be closely monitored and maintained below 180 mg/ deciliter (dL), and abnormal electrolyte levels should be corrected, especially potassium, phosphate, and magnesium, be ore starting or advancing to the goal solution. Additionally, any patient who is at high risk or re eeding syndrome should receive IVthiamine replacement prior to initiation o total parenteral nutrition (TPN) to prevent development o Wernicke’s encephalopathy. Traditionally, patients af ected with alcohol use were the hallmark high-risk patient or Wernicke’s. However, those recovering rom weight loss surgery (eg, gastric bypass) with prolonged nausea and vomiting is a newly recognized group o patients who are at risk or this complication. The solutions should be administered using a volumetric pump set at a constant rate. In general, PN lipid in usion should not exceed 382

1 g/kg/d, and dextrose in usion should be less than 5 mg/kg/min. Eventually, the PN solution can be cycled nocturnally (generally between 10 and 16 hours) in long-term PN patients, once glycemic control is achieved. Once stable, patients can have lab monitoring decreased to once or twice weekly. Patients receiving long-term PN may develop PN-associated liver dys unction (PNALD). However, alterations that occur within the rst 2 weeks o PN therapy generally resolve despite continuation o TPN. Alternate causes o liver unction test (LFT) elevation should always be ruled out, such as hepatotoxic medications, biliary obstruction, and sepsis. PNALD should be a diagnosis o exclusion rather than the rst thought in the acutely ill patient that has just been started on PN. Excess provision o IVdextrose or lipid, and de ciencies o carnitine and choline may increase the likelihood o PNALD. Provision o the appropriate amount o dextrose and carbohydrate, repleting carnitine and choline, and administering even small amounts o enteral nourishment may decrease the risk o developing PNALD. Finally, decreasing PN cycle time to less than 24 hours each day may allow or hepatic “rest” and decrease continuous insulin secretion, which may decrease atty deposits in the liver.

■ PARENTERAL ACCESS Central venous access is required or the administration o TPN because TPN solutions are hyperosmolar. Peripheral PN (PPN) solutions, which are available in some hospitals, have limited dextrose and amino acid concentrations in order to keep osmolarity lower; this improves tolerance o PN delivery via a peripheral vein, but lowers caloric density. PPN is generally not a good long-term (>3-5 days) solution or most patients and only use ul or those patients who can tolerate high volumes o uid daily. The physician must also determine the most appropriate access device or PN. See Chapter 120 (Vascular Access, or more in ormation about types and indications o catheters). SPECIAL CONSIDERATIONS

■ PANCREATITIS Pancreatitis patients require no nutritional intervention in 80% to 90% o cases as most will resume an oral diet within 7 days o admission. EN remains the pre erred route o nutritional support or the remaining patients because it is associated with a signi cant reduction in in ectious morbidity, length o stay, and mortality compared to PN. EN can be appropriately achieved by eeding into the stomach or jejunum depending on gastric emptying. O note, patients who are ed within the rst 24 to 48 hours o admission may tolerate enteral eeding better than those who start eeding later, and such early eeding is associated with substantial outcome bene ts. These bene ts diminish in patients who start eeding as late as day 4. PN should be considered in severe pancreatitis patients who cannot receive enteral eeding or prolonged periods. PN may exacerbate the in ammatory response to pancreatitis i initiated too early; ASPEN guidelines suggest not starting PN or 5 days in those with severe pancreatitis, even i enteral eeding is not possible.

■ RENAL DISEASE Dialysis patients o ten have poor oral intake, increased nutrient losses in their dialysates, and increased catabolic stress. Thus malnutrition is common in this patient population. The Kidney Disease Outcomes Quality Initiative (K/DOQI) guidelines recommend protein restriction or outpatient dialysis patients, but notably recommend that dialysis patients receive 1.2 to 1.3 g/kg o protein when hospitalized or acute illnesses. Many nutrition experts also believe that acutely ill patients who are “predialysis” should still

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A. Es tima te nutrie nt re quire me nts :

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die t ha s be e n uns ucce s s ful for 10 da ys , a nd TP N is re quire d.

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P a tie nt is a 45-ye a r-old ma n with dive rticula r a bs ce s s , a s in Figure 58-2. Adva nce me nt to a n ora l

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Ca lorie re quire me nt: 2373 ca lorie s /d (s e e Figure 58-2) Fluid re quire me nt: 30 mL/kg body we ight = 80 x 30 = 2400 mL

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P rote in re quire me nt: 1.5 g/kg/d = 80 x 1.5 = 120 g/d

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120 g prote in ÷ 2.4 L fluid = 50 g/L

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2373 tota l ca lorie s – 480 prote in ca lorie s from prote in = 1893 nonprote in kca ls

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2. Lipid conte nt (a p p roxima te ly 20%-25% of nonp rote in kc a ls )

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4 ca lorie s /g of a mino a cids x 120 g = 480 kca ls of prote in

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50 g = 5% a mino a cids pe r lite r

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2373 tota l ca lorie s – 480 prote in ca lorie s – 400 fa t ca lorie s = 1493 CHO kca ls

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3. Ca rbohydra te (CHO) conte nt (a p p roxima te ly 50%-60% of nonp rote in c a lorie s )

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Round to ne a re s t 100 = 400 kca ls lipid/d

1493 CHO kca ls ÷ 3.4 kca ls /g of de xtros e = 439 g de xtros e 439 g de xtros e ÷ 2.4 L = 183 g de xtros e /L 183 g de xtros e = 18% de xtros e pe r lite r 4. Fina l s olution* 2.4 lite rs of 18% de xtros e , 5% a mino a cids , with 400 ca lorie s (40 g) lipid/da y. *This a s s ume s a triple mix (ie , mix of ca rbohydra te , lipid, a nd a mino a cids in one ba g). S ome ins titutions will ha ng lipid s e pa ra te ly. Othe r ins titutions do not a llow for cus tomize d s olutions a nd ha ve a limite d s e le ction of s olutions from which the clinicia n choos e s to ge t clos e to the ca lorie a nd prote in ne e ds of the pa tie nt. Figure 58 5 Parenteral nutrition calculation.

receive 1.2 to 1.5 g/kg/d o protein, even i this precipitates the need or dialysis.

■ HEPATIC DISEASE Malnutrition is also highly prevalent among patients with liver disease. Laboratory markers o nutrition status may be more re ective o diminished hepatic synthetic capacity rather than nutrition. In addition, anthropometric measurements maybe altered by uid status. Previous thoughts regarding the bene ts o protein restriction in those with hepatic encephalopathy have not been supported by more recent studies. For example, Cordoba and colleagues ound no dif erences in outcomes o encephalopathy between those on normal and protein restricted diets, and that low protein diets in act caused breakdown o lean body mass. Although much research has been devoted to the evaluation o diets supplemented with branch chain amino acids (BCAAs), the routine use o BCAA-enhanced ormulas is only recommended or those with encephalopathy re ractory to luminal-acting antibiotics and lactulose therapy.

■ PREOPERATIVE NUTRITION SUPPORT Several papers indicate that malnourished patients suf er more postoperative complications than those who are adequately nourished. Weight loss o greater than 10% o body weight most consistently

predicts adverse outcomes. Buzby and colleagues developed a measure o perioperative complication risk, which they termed “nutrition risk index” (NRI) and is calculated as ollows: NRI: 1.519 × the serum albumin level (in g/L) + 0.417 × (current weight/usual weight × 100) Patients were classi ed as borderline, mildly, or severely malnourished. The patients who met criteria or severe risk with an NRI 40 mm Hg rom preoperative baseline), and abdominal aortic aneurysm repair. A case series o atal postoperative pulmonary edema in largely healthy patients ound that the average positive uid balance was 67 mL/kg/d positive, or about 5 liters in a 70-kg patient. Interestingly, another prospective evaluation o the risk o development o postoperative HF ound that lower volumes o administered uid and negative net uid balance were associated with higher rates o postoperative HF. These ndings may be explained by the lower use o intravenous uids in patients with a history o cardiac disease. Certainly, the amount o uids given in the perioperative period is an important historical act, and despite these counterintuitive ndings, it is reasonable to consider more intraoperative IV uids to be a risk actor or postoperative pulmonary edema.

e

There are ew data to guide the use o perioperative surveillance or PMI. Due to the relatively asymptomatic nature o PMI, screening with troponins and ECG greatly enhances the detection o PMI. Given the predominance and accepted pathophysiology o Type 2 PMI, it ollows that early intervention to improve supply and decrease demand could alter outcomes; however, there are no data to support this interventional approach. Moreover, there are concerns about the potential negative impacts o some interventions such as antiplatelet or anticoagulant medication administration and revascularization procedures. The ACC/AHA guidelines have evolved over time now calling into question any surveillance ECG or troponin strategy in asymptomatic patients. Other authors and societies recommend the screening o high-risk patients, as de ned by severe underlying coronary disease or active cardiac symptoms. All agree that ischemic symptoms should prompt ECG and troponin assessment, but as outlined previously this represents the minority o patients. Hope ully, interventional trials will be orthcoming to aid in the management o these complex issues.

■ DEFINITION AND DIAGNOSIS

r

■ SURVEILLANCE

Trial do not include postoperative HF in their combined cardiac endpoint. Nonetheless, it is an important postoperative complication that leads to increased morbidity, mortality, length o stay, and cost.

y

and diuretics as needed. Volume overload is an underrecognized cause o hypertension and thereby increased myocardial demand and should be addressed aggressively. Primary tachyarrhythmias such as atrial brillation with rapid ventricular response should be rate controlled or cardioverted as the situation dictates. Initiation o β-blockers in the setting o Type 2 PMI is thought to be appropriate when demand ischemia is due to hypertension and nonhypovolemic tachycardic syndromes (eg, ever). However, β-blockers should be held in the setting o hypotension and anemia-induced ischemia as they will likely worsen these processes and clinical outcomes. Postoperative anemia management to prevent and treat PMI is controversial as both postoperative anemia and liberal trans usion have been shown to worsen outcomes. For example, a retrospective study ound preoperative hemoglobin (hgb) 38°C) with no other source Leukopenia (12,000 WBC/µL) Mental status changes with no other cause in adult >70-y old And at least two o the ollowing: New onset o purulent sputum New-onset cough, dyspnea, tachycardia Rales or bronchial breath sounds (BS) Worsening gas exchange

well as clinical and laboratory ndings (Table 60-4). The ATS/IDSA guideline describes two diagnostic approaches to HAP: clinical and bacteriologic. The clinical approach bases the diagnosis on a new in ltrate on chest x-ray plus clinical evidence o in ection. The bacteriologic strategy is based on lower respiratory tract samples and is more suited to ventilated patients where there is ready access to the lower respiratory tract. The presence o a new or progressive radiographic in ltrate plus two o three clinical eatures ( ever, leukopenia or leukocytosis, and purulent secretions) yields a sensitivity o 69% with speci city o 75% and represents the most accurate clinical criteria or starting antibiotics.

■ TREATMENT Treatment strategies seek to balance the need to provide early, appropriate empiric antibiotic therapy with avoidance o excessive antibiotic exposure in both spectrum and duration. Delay in initiating appropriate antibiotics in VAP patients with severe sepsis has been shown to increase mortality, and initial inadequate drug selection, even when later adjusted, is also associated with worse outcome. Aggressive early therapy combined with de-escalation o initial antibiotics based on clinical or microbiologic data is encouraged. Empiric drug selection takes into account the epidemiologic timing and presence o MDR risk actors, previous antibiotic exposure, and the institution-/unit-speci c antibiogram. For early-onset HAP without MDR risk actors, single-agent therapy is reasonable (Table 60-2). For early-onset HAP with MDRrisk actors or late-onset HAP, a three-drug regimen is recommended (see Table 60-3). Considerations in antibiotic selection might also include pharmacodynamic properties and mechanism o action. Fluoroquinolones and linezolid achieve high concentration in bronchial secretions. Aminoglycosides and uoroquinolones are bactericidal in a concentration-dependent ashion, whereas vancomycin and β-lactams are bactericidal in a time-dependent ashion. Aminoglycosides and the quinolones also have a postantibiotic e ect and suppress antibiotic growth even a ter concentrations all. A number o new antibiotics have become available or treating hospital acquired pneumonia, including doripenem, telvancin, ce tobiprole, and avibactam. The most appropriate use o these alternatives remains to be established. Aerosolized delivery o antibiotics is another mode o treatment that may have bene t or patients who have ailed IVtherapy or have MDR organisms. 394

The patient should be reevaluated in 48 to 72 hours, and antibiotics narrowed or discontinued based on culture results and clinical response. Therapy lasting 7 to 8 days has been shown to be equally e ective to longer courses in patients receiving an appropriate initial antibiotic regimen with a good clinical response. Pseudomonas and MRSA are the exception due to signi cant rates o recurrence and should still be treated with a longer course o antibiotics.

■ COMPLICATIONS Patients who ail to respond or worsen should be reevaluated at 48 to 72 hours. Possible reasons or lack o response include the presence o a complication (empyema, lung abscess, drug ever), an alternate site o in ection (Clostridium dif cile colitis, line-related in ection), wrong diagnosis (atelectasis, pulmonary embolism (PE), ARDS, pulmonary hemorrhage, neoplasm), or wrong organism (clinically unrecognized immunosuppression). RESPIRATORY FAILURE Acute respiratory ailure is de ned as the requirement or mechanical ventilation longer than 48 hours postoperatively or unplanned reintubation or cardiac or respiratory ailure. It can be considered the most severe o the clinically signi cant postoperative pulmonary complications based on its impact on morbidity, mortality, and cost. Mortality data rom the Department o Veterans A airs National Surgical Quality Improvement Program showed an increase in 30-day mortality rom 2.3% to 29.1% in patients with respiratory ailure, and an increase in 1-year mortality rom 9.3% to 55.9%. Another study ound the rate o postoperative respiratory ailure in patients undergoing general and vascular surgery to be 3%, with 30-day mortality o 26.5%. Pulmonary complications raised median hospital costs to $62,704 compared to $5015 when the complications were absent, more expensive than thromboembolic, cardiovascular, or in ectious complications.

■ PATHOPHYSIOLOGY Postoperative acute respiratory ailure results rom the onset over minutes to hours o impaired pulmonary gas exchange severe enough to cause organ dys unction or to threaten li e. Respiratory ailure can be broadly categorized as hypoxemic respiratory ailure (respiratory insuf ciency) or hypercapnic respiratory ailure (ventilatory ailure), and the two orms may coexist. Mechanisms underlying hypoxemic respiratory ailure, de ned as an arterial pO2 o less than 60 mm Hg, include decreased FiO2, hypoventilation, impaired di usion, V/Q mismatch, and right-to-le t shunt. Most hypoxemic hospitalized patients have some combination o V/Q mismatch and right-to-le t shunt. A structural-anatomic classi cation that localizes the primary pathology to the alveoli, interstitium, cardiopulmonary vasculature, airways, or pleura may be help ul when trying to make a speci c diagnosis. In the postoperative patient, the alveoli and interstitium can be a ected by pulmonary edema, acute lung injury/ ARDS, atelectasis, and pneumonia. The vasculature can be a ected by pulmonary embolism or develop pulmonary hypertension due to hypoxic vasoconstriction and/or elevated le t atrial pressures. The airways can be a ected by exacerbations o COPD, asthma, and mucous plugging, and the pleura may be a ected by pneumothorax or pleural e usion. Hypercapnic respiratory ailure, characterized by a pCO2 greater than 45 mm Hg and respiratory acidosis, can be classi ed as drive ailure or pump ailure. Drive ailure results when the patient’s ventilatory e ort is insuf cient and can be caused by drug overdoses, general anesthesia, central nervous system (CNS) disease, and obesity hypoventilation syndrome. The most common contributors in the perioperative setting are residual sedation rom general anesthesia or the e ects o opioid analgesics on respiratory drive

■ TREATMENT The goal or management o acute postoperative respiratory ailure is to quickly and correctly identi y the underlying pathophysiologic process and provide targeted treatment that will avoid the need or intubation and mechanical ventilation. Hypoxemic respiratory ailure has a broad di erential diagnosis, and initial supportive care should be ollowed by treatment o the speci c disease process identi ed. Pneumonia or other in ection should be treated with prompt initiation o appropriate antibiotics a ter obtaining cultures. Volume overload and pulmonary edema can be treated with diuretics and additional cardiac evaluation. Bronchospasm should be aggressively treated with inhaled β-agonists and anticholinergics with systemic corticosteroids as indicated. Suspected pulmonary embolism should be expeditiously evaluated and treated as the postoperative conditions allow. With hypercapnic respiratory ailure, the most common cause o insuf cient ventilatory drive is medication e ect. Opioids are the most potent suppressor o both hypoxic and hypercapnic ventilatory drive, but other sedatives and hypnotics also cause respiratory depression. Unrecognized obstructive sleep apnea may also present as postoperative respiratory depression. CPAP or positive pressure ventilation can be initiated i needed, and precautions can be taken to minimize the use o opioids, patient controlled anesthesia, and sedative hypnotics. Respiratory arrest, inability to protect the airway and severe respiratory acidosis mandate intubation. Noninvasive ventilation (NIV) is an important tool that can be used both to prevent and also to treat postoperative acute respiratory ailure. When success ul it has been shown to decrease the need or intubation, the rate o complications, and the intensive care unit (ICU) length o stay. NIVis indicated when there is a demonstrated need or ventilatory support and no contraindications (Table 60-5). Level 1 evidence

C H A P T E R 6 0 M a n a g e m e n t o P o s t o p e r a t i v e P u l m o n a r y C o m p l i c a t

supports the use o NIV to treat COPD exacerbations, cardiogenic pulmonary edema, and to acilitate weaning rom the ventilator in patients with COPD. Level 2 evidence supports its use in postoperative respiratory ailure, community-acquired pneumonia with COPD, asthma, extubation ailure, and in do-not-intubate-status patients (Table 60-5). Noninvasive ventilation (NIV) should be initiated early when indicated to take advantage o a therapeutic window o opportunity. Improvement is expected over the rst one to two hours. I hypoxemia persists, then there may be a concomitant complication such as aspiration or pneumonia. A ter initial stabilization, a decision should be made regarding appropriate level o care. Determinants o this will include ability to manage the airway, method o oxygen delivery to maintain adequate O2 status, and the intensity o nursing care required. Intubation should not be delayed in patients who ail an NIVtrial.

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Diagnostic workup should begin with the ABCs—airway, breathing, and circulation—and treatment initiated concurrently. Supplemental oxygen should be provided and intravenous (IV) access obtained, as well as cardiac monitoring and pulse oximetry. A ocused history and physical exam will yield clues to the presence or absence o underlying cardiac and pulmonary disease. The hypoxemic respiratory ailure patient will appear tachypneic and tachycardic, perhaps with central cyanosis. The hypercapnic respiratory ailure with decreased ventilatory drive will appear hypopnic or apneic, in no respiratory distress. The ventilatory pump ailure patient will appear in respiratory distress with rapid shallow ine ective respirations. All patients should receive a chest x-ray, electrocardiogram (ECG), and routine bloodwork including CBC and serum chemistries. An arterial blood gas should be obtained in order to calculate an A—a gradient, establish whether ventilatory ailure is present, and determine acid–base status. Further diagnostic workup will be guided by the results o these initial studies. I the etiology is not apparent on initial evaluation, urther testing might include CT angiography o the chest and echocardiography.

Contraindications Absolute • Respiratory arrest • Unable to it mask Relative • Medically unstable • Unable to protect airway • Excessive secretions • Agitated, uncooperative • Recent upper gastrointestinal or airway surgery • Multiple-organ ailure

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RESPIRATORY FAILURE?

Indications Clinical observations • Moderate to severe dyspnea • Tachypnea (>24 or hypercapnic, >30 or hypoxemic) • Accessory muscle use or abdominal paradox Gas exchange • Acute ventilatory ailure: PaCO2 > 45 mm Hg, pH < 7.35 • Hypoxemia: PaO2/FiO2 < 200

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■ DIAGNOSIS—WHAT IS CAUSING THIS PATIENT’S

TABLE 60-5 Noninvasive Ventilation—Indications and Contraindications

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and level o consciousness. Pump ailure results when ventilatory demand exceeds the patient’s capability and can be caused by prolonged e ect o neuromuscular blocking agents, underlying neuromuscular disorders, electrolyte abnormalities and metabolic disturbances, pleural disorders, chest wall abnormalities, and respiratory muscle atigue. It can be aggravated by increased CO2 production in the setting o a hypermetabolic postoperative state; this is especially true in patients with underlying loss o parenchyma (emphysema) who have a decreased alveolar sur ace area available or gas exchange.

■ COMPLICATIONS Complications o postoperative respiratory ailure include increased risks related to intubation, ventilator-induced acute lung injury progressing to ARDS, VAP, GI bleeding, and DVT. COPD EXACERBATION Patients with COPD have an elevated risk o developing postoperative pulmonary complications, including an exacerbation o obstructive lung disease. Ideally these patients will have had good preoperative risk assessment, with optimization o medical management and initiation o preventive measures such as lung expansion maneuvers and smoking cessation 4 or more weeks prior to the procedure (when applicable). Postoperative management consists o continuing the preventive measures as well as maintenance o home medications. Patients with COPD have a higher prevalence o comorbid conditions such as congestive heart ailure and coronary artery disease (CAD), so they must be care ully evaluated should they become short o breath. There is also a high rate o concomitant PE with COPD, up to 20%, so this also needs to be ruled out.

■ PATHOPHYSIOLOGY A COPD exacerbation is de ned as an event in the natural course o the disease characterized by a change in the patient’s baseline dyspnea, cough, and/or sputum that is beyond normal day-to-day variations, is acute in onset, and may warrant a change in regular medication. Exacerbations are thought to be an in ammatory event, and the airway mani estations include edema, bronchospasm, and increased sputum production. Exacerbations are heterogeneous 395

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events caused by complex interactions between the host, respiratory viruses, airway bacteria, and environmental pollution, but in approximately one-third no cause is identi ed. Hyperin ation and bronchospasm lead to increased work o breathing. Progressive hypoxemia develops, producing a downward spiral that can progress to acute ventilatory ailure when the respiratory muscles atigue. COPD is associated with other comorbid conditions, including ischemic heart disease (HD), pneumonia, and diabetes mellitus (DM), as well as venous thromboembolism (VTE), and one o these can contribute.

Incentive spirometry, Coughing and deep breathing, Oral care, Understanding (patient and amily education), Getting out o bed, and Head o bed elevation. The intervention resulted in a decrease in the number o cases o pneumonia and also o unplanned intubations, and served to illustrate the bene t o a multidisciplinary e ort. Patient and amily education were eatured prominently in the bundle, and encouragement to continue the intervention post discharge could certainly produce some additional bene t. Hospitalists can also help assure adequate discharge planning or ollow-up o medical problems as well as communication with primary care to minimize the risks o readmission.

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Typical symptoms include increased breathlessness accompanied by wheezing and chest tightness, increased cough and sputum production, change in color and tenacity o sputum, and ever. Routine evaluation should include chest x-ray, routine labs, arterial blood gas, and ECG to di erentiate COPD rom other causes given the requent comorbidities.

■ TREATMENT

American Thoracic Society. Guidelines or the management o adults with hospital-acquired, ventilator-associated, and healthcareassociated pneumonia. Am J Respir Crit Care Med. 2005;171: 388-416. Cassidy MR, et al. I COUGH: Reducing postoperative pulmonary complications with a multidisciplinary patient care program. JAMASurg. 2013;148(8):740-745.

Treatment o postoperative COPD exacerbation does not di er rom typical treatment, except that other medical complications prevalent in the postoperative period, including PE and congestive heart ailure, need to be care ully considered. Lung unction can be optimized with inhaled short-acting β-adrenergic and anticholinergic agents along with systemic glucocorticoids. A short course o antibiotics may decrease duration o exacerbation. There is currently no role or methylxanthines or chest physical therapy (PT). NIV is the pre erred method o ventilatory support and has been shown to improve outcomes in COPD exacerbations. Invasive mechanical ventilation is reserved or patients who have not responded to NIV.

Duggan M, Kavanagh BP. Pulmonary atelectasis: a pathogenic perioperative entity. Anesthesiology. 2005;102:838-854.

■ COMPLICATIONS

Lawrence VA, Cornell JE, Smetana GW. American College o Physicians. Strategies to reduce postoperative pulmonary complications a ter non-cardiothoracic surgery: systematic review or the American College o Physicians. Ann Intern Med. 2006;144:596-608.

Complications o COPD exacerbation include pneumonia, progression to acute respiratory ailure, and pneumothorax. POSTACUTE CARE Postoperative pulmonary complications continue to lurk even beyond hospital discharge. Among Medicare bene ciaries who were rehospitalized within 30 days a ter a surgical discharge, 70.5% were rehospitalized with a medical condition, and pneumonia was the second most requent reason a ter heart ailure. Speci c risk actors or readmission with pulmonary complications have not been studied, but risk is likely to be reduced by e ective care transitions that include adequate patient education on continuing preventive measures at home as well as adequacy o postdischarge ollow-up. The I COUGH trial described a multidisciplinary intervention that aimed to decrease the incidence o postoperative pneumonia by standardizing use o a “bundle” o simple postoperative interventions. These included

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SUGGESTED READINGS

Ferreyra G, Long Y, Ranieri VM. Respiratory complications a ter major surgery. Curr Opin Crit Care. 2009;15:342-348. Global strategy or the diagnosis, management, and prevention o chronic obstructive pulmonary disease. GOLD Executive Summary. Am J Respir Crit Care Med. 2013;187:347-365. Johnson RG, Arozullah AM, Neumayer L, Henderson WG, Hosokawa P, Khuri SF. Multi-variable predictors o postoperative respiratory ailure a ter general and vascular surgery: results rom the patient’s sa ety in surgery study. J Am Coll Surg. 2007;204:1188-1198.

Liapikou A, et al. Pharmacotherapy or hospital-acquired pneumonia. Expert Opin Pharmacother. 2014;15(6):775-786. Nava S, Hill N. Non-invasive ventilation in acute respiratory ailure. Lancet. 2009;374:250-259. Qaseem A, Snow V, Fitterman N, et al. Clinical Ef cacy Assessment Subcommittee o the American College o Physicians. Risk assessment or and strategies to reduce perioperative pulmonary complications or patients undergoing noncardiothoracic surgery: a guideline rom the American College o Physicians. Ann Intern Med. 2006;144:575-580. Restrepo RD, Braverman J. Current challenges in the recognition, prevention, and treatment o perioperative pulmonary atelectasis. Expert Rev Respir Med. 2015;9(1):97-107.

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CHAP TER

Assessment and Management o Patients with Renal Disease Albert Q. Lam, MD Julian L. Sei ter, MD

INTRODUCTION The kidneys are responsible or several vital homeostatic processes, including the excretion o nitrogenous waste products, the regulation o uid volume and electrolytes, acid–base balance, and the production o hormones important or blood pressure regulation, erythropoiesis, and bone metabolism. They are requently a ected by disease, both acute (occurring over days to weeks) and chronic (occurring over months to years). Acute kidney injury (AKI), ormerly known as acute renal ailure, has become an increasingly common cause o hospitalization, with an incidence o 5% to 7% among hospitalized patients. Chronic kidney disease (CKD) reportedly a ects 13% o adults in the United States, and is associated with signi cant morbidity, mortality, and expense. The recent advent o automatic reporting o estimated glomerular ltration rate (eGFR) with serum creatinine by hospital laboratories has resulted in more patients being identi ed as having impaired renal unction. In order to provide the highest level o care or patients presenting with acute or CKD, the clinician should have a strong understanding o the undamental issues relevant to their evaluation and management. EVALUATION OF THE RENAL PATIENT

■ HISTORY AND PHYSICAL EXAMINATION The evaluation o the patient with kidney disease begins with a thorough history and physical examination. The clinician should identi y whether the renal disease is acute or chronic. I the patient’s previous medical records are available, this can be determined by quickly reviewing prior laboratory testing, with particular attention given to serum creatinine, blood urea nitrogen, and urinalyses. Patients who present with AKI should be questioned about recent symptoms (eg, vomiting, diarrhea, edema, dif culty voiding, decreased appetite, weight changes) and events (eg, changes in oral intake, new medications, nonsteroidal anti-in ammatory drug [NSAID] use, intravenous contrast administration, recent colonoscopy) that may help narrow the di erential diagnosis o AKI. Symptoms such as ever, rashes, arthralgias, epistaxis, and hemoptysis suggest an underlying in ammatory condition such as vasculitis. For patients who develop AKI during their hospitalization, recent hospital events—including episodes o hypotension, recent diagnostic and therapeutic procedures, and initiation o new medications—should be reviewed. All patients presenting with AKI or CKD should be questioned about symptoms associated with uremia, including atigue, nausea, vomiting, pruritus, metallic taste, lethargy, and con usion, since these symptoms may indicate the need or dialysis. Patients should be asked whether they have a prior history o kidney disease or other relevant systemic diseases, such as diabetes and hypertension. In patients with CKD, who may or may not be presenting with an acute kidney-related problem, the clinician should establish the chronicity, severity, and cause o the underlying kidney disease. In patients with end-stage renal disease (ESRD), in ormation about the patient’s nephrologist, outpatient dialysis unit, and regular dialysis schedule (including the timing o the last dialysis session) should be obtained and conveyed to the clinicians and other health care providers who will be acilitating the patient’s dialysis during the hospitalization. The clinician should also obtain a complete and current list o the patient’s medications, including prescription medications as well as all over-the-counter medications, herbal remedies, and supplements. A amily history o kidney disease or other systemic illnesses should also be documented. 397

essential or the diagnosis and management o most renal diseases. In prerenal acute kidney injury, the presence o hypervolemia (eg, elevated jugular venous pressure, pulmonary congestion, peripheral edema) suggests decreased renal per usion rom congestive heart ailure or cirrhosis, whereas hypovolemia (postural pulse increase >30 beats/min, severe postural dizziness, dry axilla or mucous membranes) would be more consistent with volume depletion rom bleeding or gastrointestinal losses. To best assess the jugular venous pulsation, the patient should be reclined with the head elevated at 30° to 45°, and the elevation o the right internal jugular vein above the sternal angle should be measured. Certain physical ndings are associated with speci c renal diseases (Table 61-1). Palpable purpura may be observed in vasculitic processes such as

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The physical examination starts with a review o the patient’s vital signs. While ever should always raise suspicion or an in ection, particularly in dialysis patients or immunosuppressed patients, it can also be observed in the setting o acute glomerulonephritis, vasculitis, and allergic interstitial nephritis. Blood pressure may be elevated (eg, in acute nephritic syndrome, malignant hypertension, scleroderma, long-standing kidney disease), normal, or low (eg, in volume depletion, sepsis, cirrhosis, heart ailure). Fluid intake and output should be reviewed to help determine volume status and the need or uid repletion, diuresis, or dialysis. Key aspects o the exam include the bedside determination o volume status and a search or physical signs associated with speci c kidney diseases and uremia. Assessment o volume status is

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TABLE 61-1 History and Physical Examination Findings in Renal Disease

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Renal Disease Prerenal acute kidney injury

Intrarenal acute kidney injury Glomerular

Interstitial

ATN Vascular

Postrenal acute kidney injury

Nephrotic syndrome

Uremia

History • Volume depletion (hemorrhage, vomiting, diarrhea, diuretics, burns) • Heart ailure • Cirrhosis • Medications (NSAIDs, ACE inhibitors/ARBs, cyclosporine, tacrolimus) • Radiocontrast exposure • Gross hematuria or cola-colored urine • Cough and hemoptysis (Goodpasture syndrome) • Epistaxis, sinusitis, hemoptysis, arthralgias, (Wegener, Churg-Strauss) • Rash, arthralgias (systemic lupus erythematosus) • Recent respiratory in ection (postin ectious glomerulonephritis, IgA nephropathy) • Fever, arthralgias, rash • Medications (NSAIDs, antibiotics) • Episode o hypotension • Medications (aminoglycosides, amphotericin B, cisplatin) • Trauma, muscle necrosis (rhabdomyolysis) • History o multiple myeloma • History o atherosclerosis • Recent vascular intervention • Anticoagulation • Flank pain (renal vein thrombosis) • Urinary urgency, hesitancy, oliguria or anuria • Gross hematuria • Flank pain, renal colic • History o nephrolithiasis • Medications (acyclovir, indinavir, anticholinergics) • Weight gain • Foamy urine • Medications (NSAIDs, gold, penicillamine) • Fatigue, lethargy, con usion, seizures • Anorexia, nausea, vomiting • Pruritus, metallic taste, bleeding

Physical Exam Findings • Orthostatic hypotension, dry mucous membranes and axillae • Elevated JVP, +S3, lung rales, edema (heart ailure) • Jaundice, ascites, edema (cirrhosis)

• Fever, palpable purpura, arthritis

(vasculitis) • Saddle-nose de ormity (Wegener) • Oral ulcers, rash, arthritis, pericardial rub (SLE)

• Fever, skin rash • Hypotension • Warm (early sepsis) or cold extremities

(late sepsis) • Elevated BP • Livedo reticularis, ischemic extremities

• Distended bladder • Enlarged prostate • Palpable abdominal or pelvic masses

• Anasarca, ascites, edema

• Asterixis • Pericardial or pleural riction rub • Hal -and-hal nails • Dry and atrophic skin, pallor,

hyperpigmentation, ecchymoses, uremic rost ACE, angiotensin-converting enzyme; ARB, angiotensin receptor blocker; BP, blood pressure; JVP, jugular venous pressure; NSAID, nonsteroidal anti-in lammatory drug; SLE, systemic lupus erythematosus.

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Blood urea nitrogen and creatinine Blood urea nitrogen (BUN) and creatinine are nitrogenous end products o metabolism that rise in the setting o renal disease. Urea is ormed rom ammonia derived rom protein breakdown, while creatinine is a byproduct o muscle creatine metabolism. Urea and creatinine are reely ltered by the kidneys but handled di erently in the tubular system. Urea is partly reabsorbed in the proximal tubule and inner medullary collecting duct, while creatinine is secreted to a small extent by the tubules. Despite these con ounding e ects o tubular handling, BUN and creatinine are still the most commonly used biomarkers o renal unction. Neither test is ideal or the

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Serum electrolytes are essential to the evaluation o the patient with acute and chronic renal disease. Both hyponatremia and hypernatremia may be seen in patients with kidney disease. Impaired renal unction decreases renal potassium excretion, and may lead to potentially li e-threatening hyperkalemia in oliguric or anuric patients. The serum potassium concentration may not be an accurate indicator o total body potassium stores, since most o the total body potassium is con ned to the intracellular uid compartment. For example, in diabetic ketoacidosis, patients requently have elevated serum potassium levels despite diminished total body potassium stores. Serum chloride and bicarbonate levels are use ul in the assessment o volume and acid–base status. The serum anion gap, used in the assessment o metabolic acidosis, can be calculated rom serum sodium, chloride, and bicarbonate concentrations (AG = Na+ – [Cl– + HCO3–]). Serum calcium, phosphorus, and magnesium levels yield important in ormation about renal tubular unction and bone mineral metabolism. Hyperphosphatemia and hypocalcemia are common in patients with acute and chronic renal disease, and contribute to the development o secondary hyperparathyroidism.

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All patients with kidney disease, both acute and chronic, should have their kidney unction assessed by estimation o the glomerular ltration rate (GFR). GFR may be estimated by measuring serum creatinine, calculating the creatinine clearance, or using estimation equations such as the Cockcro t-Gault ormula, the Modi cation o Diet in Renal Disease (MDRD) equation, or the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) equation. The normal GFR in a healthy adult is >90 mL/min. GFR decreases with age, at a rate o approximately 1 mL/min/y a ter age 35. Elderly patients may also have lower-creatinine levels due to decreased muscle mass. Measurement o serum creatinine is the most requently used surrogate or GFR. As serum creatinine concentrations are a ected by muscle mass, dietary protein intake, and certain medications, it is not the most accurate method o estimating GFR. The Cockcro t-Gault, MDRD, and CKD-EPI equations take into account serum creatinine, as well as other de ned actors such as age, race, gender, and weight. They were designed to estimate GFR in patients with established CKD, and are most use ul or this purpose. While the per ormance o these equations has been evaluated in a variety o di erent racial and ethnic populations with and without kidney disease, they should still be interpreted with caution in speci c patient populations that have yet to be well validated, including individuals with normal or nearnormal renal unction, children, and elderly individuals. The CKD-EPI equation may be superior to the MDRD equation in estimating GFR in patients with normal or mildly impaired (GFR >60 mL/min/1.73 m 2) renal unction. Serum creatinine and the estimation equations should only be used to approximate GFR in patients with stable kidney unction (unchanging serum creatinine). I the clinician is uncertain about the accuracy o GFR estimation, a 24-hour urine collection can be per ormed to calculate creatinine clearance.

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The physical ndings o uremia are highly variable. Uremic pericarditis or pleuritis may be present, as mani ested by a pericardial or pleural riction rub, respectively. The pericardial riction rub classically has three components, one systolic and two diastolic, and a scratchy or grating quality. Skin and nail changes may include uremic rost (the ne residue o excreted urea on the sur ace o the skin), skin hyperpigmentation, or hal -and-hal nails (sharp demarcation between proximal and distal nail halves). Patients with uid retention may have pulmonary congestion or peripheral edema. Neurological ndings include con usion, coma, asterixis, and sensory de cits. The presence o these physical ndings, especially the pericardial riction rub and neurological abnormalities, may indicate the need or dialysis.

Estimated glomerular filtration rate

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Key aspects o the physical examination include: • Determination o the patient’s volume status; • Identi cation o physical mani estations that suggest speci c renal disease conditions; • Search or signs o uremia.

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early detection o renal disease. Elevated serum BUN is sometimes attributable to nonrenal actors, such as high-protein intake, upper gastrointestinal tract bleeding, and high catabolism states, such as ever, corticosteroids, and burns. Serum creatinine may also be a ected by many actors, including muscle mass and medications that impair tubular creatinine secretion, such as trimethoprim and cimetidine. Though BUN and creatinine are the traditional primary biomarkers o renal injury, their use may decrease in the uture in avor o more sensitive and speci c biomarkers, including neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), and cystatin C.

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granulomatosis with polyangiitis ( ormerly known as Wegener’s granulomatosis), microscopic polyangiitis, Churg-Strauss syndrome, or Henoch-Schönlein purpura. Abdominal bruits with re ractory hypertension and progressive renal ailure are suggestive o renovascular disease. Funduscopic examination can reveal arteriolar narrowing, hemorrhages, exudates, or papilledema— ndings consistent with chronic hypertension.

PRACTICE POINT Laboratory testing • Serum creatinine and the estimation equations should only be used to approximate GFR in patients with stable kidney unction (unchanging serum creatinine). • The examination o the urinary sediment by microscopy can provide use ul diagnostic in ormation about both acute and chronic kidney disease. Urine particles lyse easily a ter collection, and there ore urine samples should be examined within 2 to 4 hours o acquisition. The pathognomonic nding o ATN on urinary sediment is the presence o coarse muddy brown granular casts, which represent extensive renal tubular epithelial cell injury. • In acute kidney injury, a ractional excretion o sodium (FENa) in combination with clinical history and other lab tests may help di erentiate between prerenal etiologies and acute tubular necrosis (ATN). 399

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While a FENa o 2% is usually indicative o ATN. However, a FENa < % 1 can also be seen in contrast-induced nephropathy, rhabdomyolysis, acute glomerulonephritis, hepatorenal syndrome, early urinary obstruction, acute interstitial nephritis, and even ATN. Furthermore, a FENa may be dif cult to interpret in the setting o a patient taking diuretics. In such cases, calculating the ractional excretion o urea (FEUrea) may help to di erentiate prerenal AKI (FEUrea < 35%) rom ATN (FEUrea 50%-65%). In nonanion gap metabolic acidosis, one can calculate a urine anion gap (UAG) to help di erentiate between gastrointestinal losses o bicarbonate (eg, diarrhea) and renal tubular acidosis using the ollowing ormula: (urine Na+ + urine K+) – urine Cl–. A negative UAG is consistent with gastrointestinal losses, whereas a positive UAG is requently seen with renal tubular acidosis. Serum enzymes Serum enzyme levels should be interpreted cautiously in patients with impaired renal unction. Cardiac enzymes, including cardiac troponin T (cTnT), cardiac troponin I (cTnI), and the muscle/brain (MB) isoenzyme o creatine kinase (CK-MB), are o ten elevated in acute or chronic kidney disease, even in the absence o acute

Doppler ultrasonography Doppler ultrasonography can provide in ormation about the presence and ow o blood through the vessels o the kidney. Highvelocity or disorganized ow patterns can be seen in patients with hemodynamically signi cant renal artery stenosis. Elevated vascular

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The primary role o renal magnetic resonance imaging (MRI) is the evaluation o renal masses. MRI can e ectively di erentiate benign versus malignant lesions in the kidney, especially when CT scanning with intravenous iodinated contrast is contraindicated or i ultrasonographic and CT scans are nondiagnostic. MR angiography (MRA), which involves the administration o intravenous gadolinium, has become the modality o choice in the evaluation o renovascular disease. According to one meta-analysis, gadolinium-enhanced MRA had a reported sensitivity o 97% and speci city o 85% or the detection o renal artery stenosis. However, the use o gadoliniumbased contrast agents in moderate to severe CKD has been associated with the development o nephrogenic systemic brosis (NSF), with debilitating brosis o the skin, joints, eyes, and other internal organs. Patients with an estimated GFR 6 hours. Although both the RIFLE and AKIN classi cation systems have been validated in a variety o clinical settings, their utility at this time appears to be greater or research use than or the bedside. AKI can be divided into three diagnostic categories based on the anatomic location o injury: prerenal, intrarenal, and postrenal (Table 61-3). It can be urther subdivided into oliguric (urine output < 400 mL/d) and nonoliguric (urine output > 400 mL/d), with patients producing less than 100 mL urine/d considered to be anuric. These distinctions are important, given that epidemiological studies have ound that oliguria in the setting o AKI is an independent predictor o mortality. Oliguric AKI is more characteristic o prerenal etiologies and urinary obstruction, while nonoliguric AKI is commonly seen in intrarenal AKI. Anuria is uncommon and is usually associated with complete urinary tract obstruction, bilateral renal in arction, renal vein thrombosis, cortical necrosis, or high-grade ischemic acute tubular necrosis.

■ PRERENAL Prerenal AKI is de ned as a reduction in GFR caused by hypoper usion o the kidney. In most cases o prerenal AKI, the kidneys are morphologically normal. Prerenal AKI can be divided into conditions that cause volume depletion and conditions that induce renal vasoconstriction. True volume depletion may result rom hemorrhage or gastrointestinal, urinary, or cutaneous uid losses. E ective volume

depletion re ers to decreased e ective circulating volume in the setting o normovolemia or hypervolemia, and can result rom marked vasodilatation as seen in the setting o sepsis, heart ailure, cirrhosis, and third-spacing. Renal vasoconstriction is most o ten caused by medications, including angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), NSAIDs, intravenous iodinated contrast agents, and the immunosuppressant drugs cyclosporine and tacrolimus. Patients with prerenal AKI usually present with an elevated BUN and creatinine, and the ratio o BUN to creatinine is classically greater than 20:1. Urinalysis o ten reveals an elevated speci c gravity without signi cant hematuria or proteinuria. The urinary sediment is typically bland but may show hyaline casts. The kidneys, in an appropriate response to the reduction in renal per usion, maximize sodium and water reabsorption. Urine sodium is typically low, and the FENa and urea are 200%-300% >300%

RIFLE Stages Risk (R) Injury (I) Failure (F)

AKIN Stages 1 2 3

Loss (L) End-stage kidney disease (E)

Complete loss o kidney unction or >4 wk Need or renal replacement therapy or >3 mo

AKIN, Acute Kidney Injury Network; RIFLE, Risk-Injury-Failure-Loss-ESRD.

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AKIN Increase in Serum Creatinine ≥0.3 mg/dL or ≥150%-200% >200%-300% >300% or acute renal replacement therapy

RIFLE and AKIN Urine Output 6 h 12 h 1%, but this is not always reliable. Urinalysis may show mild proteinuria (1.4 mg/dL or patients with GFR 50 mL/ min/1.73 m 2 100% 75% 100%

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Drug Acyclovir (oral) Allopurinol Ampicillin/ sulbactam (Unasyn) Ce azolin (Ance ) Ce tazidime (Fortaz) Ce triaxone (Rocephin) Cipro loxacin

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TABLE 61-4 Dosing Adjustments or Commonly Prescribed Medications in Patients with Impaired Renal Function

2.25 g IVevery 6 h (GFR 20-40) 2.25 g IVevery 8 h 2.25 g IVevery 8 h (GFR < 20) Usual dosage Start at 5 mg daily Start with 1 g IVevery 12 h (GFR 40-60) Start with 1g IVevery 24 h (GFR < 40) Determine dose by serum level monitoring

DVT, deep vein thrombosis; GFR, glomerular iltration rate; IV, intravenous; SC, subcutaneous.

support, parenteral or enteral, is requently required in order to ensure adequate delivery o protein and energy, prevent urther metabolic derangements and complications, improve wound healing, bolster the immune system, and decrease mortality. It should be noted that, in spite o the available treatment modalities and advances in dialysis technology, mortality in patients with AKI remains high, with a rate o approximately 50% to 80% in critically ill patients. When to consult a nephrologist There are a number o common clinical scenarios that are considered nephrologic emergencies, and immediate evaluation by a nephrologist should be requested.

PRACTICE POINT Indications or emergent nephrology consultation include: • Volume overload in an oliguric or anuric patient • Hyperkalemia with serum potassium >5.5 to 6 mEq/L and/or associated with changes on the electrocardiogram and other electrolyte abnormalities, especially in an oligoanuric patient • Toxic overdoses that can be treated with hemodialysis, including ethylene glycol, methanol, and lithium • Symptomatic or severe hyponatremia • Hypertensive crises • Rapidly progressive glomerulonephritis • Microangiopathic hemolytic anemias, including thrombotic thrombocytopenic purpura and hemolytic uremic syndrome

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Indications for renal biopsy

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Percutaneous renal biopsy can be instrumental to the diagnosis o AKI. This procedure is typically per ormed under ultrasonographic guidance with local anesthesia, although CT-guided biopsy is an alternative in morbidly obese patients. In the setting o AKI, a renal biopsy may be most help ul either when the diagnosis o acute glomerulonephritis is suspected or when the cause o renal ailure is unknown. Other common indications or per orming a renal biopsy include unexplained glomerular hematuria, signi cant proteinuria, and nephrotic syndrome. Absolute contraindications to percutaneous renal biopsy include uncontrolled moderate to severe hypertension, uncontrolled bleeding diathesis or severe anemia, an uncooperative patient, and a solitary unctional kidney. Relative contraindications include anatomic abnormalities o the kidney that may increase the risk o the procedure, skin in ection overlying the biopsy site, active renal or perinephric in ection, hydronephrosis, and the presence o multiple renal cysts or a renal tumor. The most common complication ollowing percutaneous renal biopsy is bleeding, which usually occurs within 12 to 24 hours postbiopsy. Other complications include pain, gross hematuria, and in ection. Chronic war arin anticoagulation is not a contraindication to renal biopsy. However, the need and urgency or biopsy must be weighed against the risk o thrombosis i anticoagulation is stopped. In patients chronically taking aspirin or other antithrombotic agents, these medications should be held as soon as it is known that a biopsy will be per ormed (ideally 1-2 weeks prior to the procedure) and should not be resumed until 1 to 2 weeks a ter the procedure. Heparin should be stopped at least 6 hours prior to the biopsy, and held or at least 12 to 24 hours postbiopsy. Indications for dialysis Dialysis is initiated to prevent and treat the li e-threatening complications and uremic symptoms associated with severe AKI. Generally accepted indications to start dialysis in the setting o AKI include (1) severe metabolic acidosis; (2) hyperkalemia, especially i electrocardiographic abnormalities are present; (3) volume overload re ractory to the use o diuretics; and (4) uremic signs and symptoms, such as pericarditis, altered mental status, or seizures. The optimal timing o dialysis initiation has not been well established. Although a ew retrospective and nonrandomized trials have ound that earlier initiation o dialysis may improve survival, these results have yet to be tested in a large prospective randomized clinical trial.

aminoglycosides. Patients may present postoperatively with either an acute elevation in serum creatinine or reduced urine output. A number o principles can guide the evaluation and management o postoperative AKI: 1. Identif cation o inciting actors. Perioperative records and owsheets should be thoroughly reviewed or evidence o hypotension, signi cant intraoperative or postoperative uid losses (eg, blood and intravascular uid losses, insensible losses, drainage losses, and third-spaced uid losses), and the administration o potentially nephrotoxic agents (eg, NSAIDs or pain control or hydroxyethyl starches used or volume resuscitation). 2. Hemodynamic monitoring. Patients should have close perioperative hemodynamic monitoring, and i necessary, invasive monitoring with intra-arterial, central venous, or pulmonary arterial catheters. 3. Maintenance o adequate renal per usion. Though no optimal mean arterial pressure (MAP) has been established to ensure adequate renal per usion, maintaining a MAP o at least >65 mm Hg and pre erably >75 to 80 mm Hg is recommended. 4. Optimization o volume status. Intravenous uid hydration should be administered to optimize renal per usion in patients with volume depletion or hemodynamic instability. Patients who develop oliguria are o ten hypovolemic and should be given a uid challenge. I they respond avorably with an improvement in urine output or hemodynamic parameters, more uid challenges can be attempted. 5. Avoidance o nephrotoxic agents. Concomitant use o nephrotoxic medications is a risk actor or the development o postoperative AKI. I iodinated contrast agents must be used or diagnostic or therapeutic purposes, the smallest amount o nonionic iso-osmolar volume o contrast should be used. Other drugs such as NSAIDs, aminoglycosides, and amphotericin B should be avoided i possible. Patients who take ACE inhibitors or ARBs on a chronic basis should discontinue these medications prior to surgery, since chronic ACE inhibition reportedly increases the risk o postoperative AKI. 6. Pharmacologic agents. Several agents, including dopamine, enoldapam, atrial natriuretic peptide, mannitol, calcium-channel blockers, and loop diuretics, have been tested or their ability to prevent postoperative AKI. The results o these studies are inconclusive, and there is insuf cient evidence to recommend their use at this time.

■ SPECIFIC SYNDROMES

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Postoperative renal failure

Hepatorenal syndrome

Postoperative AKI resulting in oliguria and an elevated serum creatinine is one o the most common and serious complications o surgery, representing 18% to 47% o all cases o hospital-acquired AKI. It is associated with a higher risk or serious in ections and sepsis, greater costs o hospitalization, and increased mortality ollowing both cardiac and noncardiac surgery. Up to 30% o patients undergoing cardiovascular and thoracic surgeries develop postoperative AKI, and up to 7% o these patients need renal replacement therapy. Furthermore, postoperative AKI that requires dialysis carries an inhospital mortality rate o 60% to 80%. The most common cause o postoperative AKI is ischemic ATN resulting rom decreased renal per usion during surgery. Common surgical scenarios or the development o ATN include supra- or in rarenal aortic cross-clamping in vascular surgery and cardiopulmonary bypass during cardiac surgery. Risk actors or the development o postoperative AKI include preexisting renal dys unction, diabetes mellitus, advanced age (>65), major vascular surgery, cardiopulmonary bypass times greater than 3 hours, and recent exposure to nephrotoxic agents including contrast dyes, NSAIDs, and

Hepatorenal syndrome (HRS) is a unctional orm o AKI that occurs primarily in patients with cirrhosis and ascites. The pathophysiology o HRS is thought to be due to nitric oxide–induced vasodilation o the splanchnic circulation, leading to marked intrarenal arterial vasoconstriction and a reduction in GFR. There are two types o HRS: type 1 HRS is the rapidly progressive orm o the disease characterized by a doubling o the initial serum creatinine level to greater than 2.5 mg/dL over a period o less than 2 weeks. The prognosis o patients with type 1 HRS without liver transplantation is generally very poor. Type 2 HRS is a more moderate orm o renal ailure characterized by serum creatinine levels between 1.5 and 2.5 mg/dL and associated with a more indolent course and improved survival compared to type 1 HRS. Both type 1 and type 2 HRS can occur spontaneously or develop a ter a precipitating event, most commonly a bacterial in ection such as spontaneous bacterial peritonitis (SBP). Diagnostic criteria or HRS were recently revised by the International Ascites Club (IAC) in 2015, taking into account newer de nitions o AKI, and now include the ollowing: (1) cirrhosis with ascites; (2) increase in serum creatinine o ≥0.3 mg/dL within 48 hours, or

1. Type o contrast agent. The choice o contrast agent is important, since higher-osmolar agents are associated with greater nephrotoxicity. In high-risk patients, nonionic isoosmolar (eg, iodixanol) and low-osmolar (eg, iohexol, ioversol, iopamidol) contrast agents have been shown to have lower nephrotoxicity. 2. Volume expansion. Intravenous hydration is clearly bene cial in the prevention o contrast-induced AKI, though the optimal hydration uid has yet to be determined. The current evidence indicates that isotonic uids (either normal saline or sodium bicarbonate) are more protective than hal -normal saline. Although initial clinical trials showed a bene t to using sodium bicarbonate over normal saline, more recent evidence has not con rmed these ndings. The rate and timing o hydration are also unclear. I using normal saline, one possible regimen is 1 mL/kg or 6 to 12 hours be ore the procedure, ollowed by 1 mL/kg or 6 to 12 hours a ter the procedure. Alternatively, i using isotonic sodium bicarbonate (three 50 mL ampules each containing 50 mEq o sodium bicarbonate in 850 mL o 5% dextrose in water), one possible regimen is a bolus o 3 mL/kg or 1 hour prior to the procedure, ollowed by an in usion o 1 mL/kg or 6 hours a ter the procedure. 3. N Acetylcysteine. Though requently used in the prevention o contrast-induced AKI, N-acetylcysteine has had inconsistent results in most clinical studies and meta-analyses. While some trials have reported signi cant protection, others have

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Intrarenal • Acute interstitial nephritis

• Acute tubular necrosis

Postrenal

n t a n d M a n a g e m e n t o P a t t h R e n a l D i

Drugs ACE inhibitors Angiotensin receptor blockers Cyclosporine IL-2 Iodinated contrast agents NSAIDs Tacrolimus NSAIDs Penicillin analogues (na cillin, oxacillin) Cephalosporins Sul a drugs (sul amethoxazole, thiazide diuretics) Ri ampin Cipro loxacin Proton-pump inhibitors Aminoglycoside antibiotics Amphotericin B Cisplatin Iodinated contrast agents HIVmedications (ade ovir, ritonavir, teno ovir) Acyclovir Analgesics Indinavir Methotrexate

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Nephrotoxicity Prerenal

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TABLE 61-5 Nephrotoxic Drugs in Acute Kidney Injury

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Therapeutic agents requently cause AKI in the hospital setting. The clinician should suspect drug toxicity when there is an acute rise in serum creatinine associated with the recent administration o a drug. As with AKI, drug nephrotoxicity can be divided into prerenal, intrarenal, and postrenal mechanisms. The most common mechanisms involve direct renal tubular injury resulting in ATN or renal interstitial in ammation leading to AIN. Other orms o injury include tubular obstruction due to drug precipitation, alterations in intrarenal blood ow, and, less commonly, glomerular disease. Drugs that are commonly associated with nephrotoxicity and their primary mechanisms o toxicity are listed in Table 61-5.

a

Contrast-induced nephropathy is one o the most common causes o AKI in the hospital setting, with incidence rates ranging rom 30%. Contrast-induced AKI is commonly de ned as an increase in serum creatinine (either an absolute increase o 0.5 mg/dL or a 25% increase rom baseline) within the rst 24 hours a ter contrast exposure. The mechanism o injury involves renal vasoconstriction, impaired vasodilation, medullary hypoxia, and direct tubular cell damage. Preexisting renal impairment (eGFR < 60 mL/min) and diabetes mellitus are the most important risk actors or contrastinduced AKI, though heart ailure, hypovolemia, nephrotoxic drugs, and hemodynamic instability are also signi cant risk actors. A number o preventive strategies have been studied in patients at risk or contrast-induced AKI:

Drug toxicity

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Contrast induced nephropathy

shown less substantial or even insigni cant bene ts. Given its relatively benign side e ect pro le and low cost, however, N-acetylcysteine is still o ten recommended as an adjunctive agent to IVhydration. In at-risk patients, it can be administered as 600 or 1200 mg orally twice daily on the day be ore and the day o the procedure. 4. Diuretics. The use o diuretics, particularly mannitol and urosemide, has not shown any bene t and may actually be harmul to patients. 5. Hemodialysis/hemof ltration. Although iodinated contrast agents are removable by dialysis, there is currently no de nitive evidence to suggest that prophylactic hemodialysis or hemo ltration reduces the incidence o contrast-induced AKI.

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≥50% increase in serum creatinine rom baseline, known or presumed to have occurred within the past 7 days; (3) no response a ter two consecutive days with diuretic withdrawal and volume expansion with albumin 1 g/kg body weight; (4) absence o shock; (5) no current or recent treatment with nephrotoxic drugs; and (6) no macroscopic signs o structural kidney injury (proteinuria >500 mg/d, microhematuria with >50 red blood cells per highpower eld, and/or abnormal renal ultrasonography). With proper medical treatment, HRS is potentially reversible. Type 1 HRS can be treated with vasoconstrictors (eg, terlipressin, midodrine in combination with octreotide, norepinephrine) combined with albumin. Transjugular intrahepatic portal shunt (TIPS) may be considered in patients with type 1 HRS with either partial response (decrease in serum creatinine to ≥0.3 mg/dL above the baseline value) or no response (no regression in AKI) to medication. There is currently no de nitive evidence demonstrating a bene t to using vasoconstrictors in patients with type 2 HRS. In patients being treated or SBP, prophylaxis with albumin is indicated, as this has been shown in one randomized clinical trial to lower the incidence o HRS by 66%, with signi cant reductions in 30-day mortality rates. The suggested dose o albumin is 1.5 mg/kg body weight on the rst day, ollowed by 1 mg/kg body weight on the third day. Liver transplantation remains the treatment o choice or both type 1 and type 2 HRS.

ACE, angiotensin-converting enzyme; HIV, human immunode iciency virus; IL, interleukin; NSAID, nonsteroidal anti-in lammatory drug.

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Drug-induced ATN is seen with the administration o medications that are excreted primarily by the kidneys, including aminoglycoside antibiotics, amphotericin B, and cisplatin. Aminoglycosides, commonly prescribed or the treatment o Gram-negative bacterial in ections, cause dose-dependent ATN with a requency ranging rom 10% to 20%. Neomycin causes the greatest nephrotoxicity; gentamicin, tobramycin, and amikacin cause intermediate nephrotoxicity; and streptomycin causes the least nephrotoxicity. It should be recognized that aminoglycoside toxicity may ollow oral administration o neomycin in cirrhotics, joint lavage a ter orthopedic procedures, and skin applications in burn patients. ATN typically develops 5 to 10 days a ter initiation o aminoglycoside treatment, and is generally nonoliguric. The kidney injury is usually reversible with withdrawal o the drug, but renal replacement therapy may be necessary in some cases. AIN accounts or 3% to 15% o all drug-induced AKI. The most common o ending agents include NSAIDs, penicillins, cephalosporins, sul onamides, ri ampin, cipro oxacin, and proton-pump inhibitors. While the onset o drug-induced AIN has been reported as early as a ew days a ter a secondary exposure to a medication, it usually occurs 7 to 14 days and as late as weeks to months a ter a primary exposure. AIN is typically reversible with withdrawal o the drug, though renal recovery may take weeks to months. Treatment o AIN with steroids has an unclear bene t, though some case series suggest that a short course o prednisone (1 mg/kg/d or up to 4 weeks) may increase the rate o recovery. Drug-induced urinary obstruction generally results rom the precipitation o drugs within the renal tubules or ureters. Crystal-induced AKI and nephrolithiasis may occur with acyclovir and indinavir. Certain analgesics containing aspirin, phenacetin, and ca eine may cause renal papillary necrosis, and with sloughing o the necrotic tissue that may lead to acute ureteral obstruction. Patients with drug-induced urinary obstruction may present with symptoms o renal colic and acute urinary tract obstruction. Management involves hydration, pain control, and discontinuation o the medication, although invasive removal o the stones may be required in severe cases. A number o medications are known to modulate renal hemodynamics and cause a prerenal type o AKI. When renal per usion is decreased, regulation o GFR involves vasodilation o the a erent arteriole and vasoconstriction o the e erent arteriole. Drugs that inhibit these compensatory mechanisms urther impair renal per usion and lead to AKI. These agents include NSAIDs, ACE inhibitors, ARBs, cyclosporine, tacrolimus, and iodinated contrast agents. NSAIDs inhibit the production o prostaglandins, which mediate a erent arteriolar vasodilation. In patients with normal renal unction, this e ect is largely inconsequential, but in those whose baseline renal per usion is already impaired (eg, patients with heart ailure or volume depletion), it can signi cantly reduce intrarenal blood ow and renal unction. In contrast, ACE inhibitors and ARBs selectively block angiotensin II-mediated vasoconstriction o the e erent arteriole. An increase in serum creatinine o up to 30% is acceptable with ACE inhibitors and ARBs, given the proven long-term renal protective e ects o these medications, but more signi cant loss o renal unction may be observed in patients with decreased renal per usion or renovascular disease. Cyclosporine and tacrolimus, calcineurin inhibitors widely used as immunosuppressants, cause intense a erent and e erent arteriolar vasoconstriction. Most patients taking these medications experience a reduction in GFR within weeks to months o starting therapy. As this e ect is generally reversible and thought to be dose related, cyclosporine-, or tacrolimus-induced AKI can usually be managed with dose reduction. Chemotherapy induced nephrotoxicity Several agents used to treat cancer are toxic to the kidneys and may cause AKI. Intravascular volume depletion, simultaneous 408

administration o other nephrotoxic drugs or iodinated contrast agents, urinary tract obstruction, and underlying renal disease increase the risk o chemotherapy-induced nephrotoxicity. Cisplatin can cause dose-related acute tubular necrosis and signi cant hypomagnesemia due to renal magnesium wasting. AKI may be reversible, though the repeated administration o cisplatin may lead to chronic and irreversible kidney damage. Aggressive hydration with intravenous uids, particularly isotonic normal saline, can increase urine volume and ow and reduce the risk o cisplatin toxicity. Newer-generation platinum compounds such as carboplatin and oxaliplatin are generally less nephrotoxic, but may also cause acute tubular injury. Methotrexate is not nephrotoxic at low doses (45 g]) and no intraoperative or postoperative sodium level was obtained, serum sodium and serum osmolalities should be ordered immediately. Patients with TURS will need their volume status stabilized and hyponatremia corrected. Blood pressure may transiently increase due to aggressive uid replacement; this will resolve as uid passes through the cellular membrane into the cell. Usually the patient should be managed in a step-down or intensive care unit.

Hypertension

Nausea ± vomiting

■ HEMATURIA FOLLOWING ENDOSCOPIC SURGERY

TABLE 67-2 Symptoms Observed in Transurethral Resection Syndrome (TURS) Neurologic Coma

PRACTICE POINT

Bradycardia Dyspnea

Angina

Respiratory depression

With any endourologic resection, the amount o postoperative bleeding will largely depend on the extent o tissue resected. Arterial bleeds typically present with acute onset o hematuria, while venous bleeds will develop gradually. Postoperative bleeds may be due to patient-speci c actors such as increased blood pressure as the patient emerges rom anesthesia, or a coagulopathic state. A bleeding vessel is compressed with bladder distension during surgery; reinspection with a reduced volume in the bladder will o ten identi y bleeding vessels be ore the surgery is complete.

C H A P T E R 6 7 U r o l o g

gentle traction (with a heavy abric tape secured to the leg) to orce the catheter balloon into the de ect. Bed rest is generally necessary during this maneuver to avoid irritation o the bleeding sinus. This traction should be released each morning to reassess the hematuria and release the tension on the tissues. I heavy traction is le t or too long, it can result in necrosis o the urethral sphincter muscle or prostate tissue. Signi cant and early postoperative hematuria is likely o arterial origin and usually requires a return to the OR or inspection and potentially ulguration. Patients that develop hemodynamic instability nonresponsive to uid resuscitation may also require re-exploration in the OR. The urologist should be consulted immediately or assessment.

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A three-way catheter in place ollowing endourological procedures allows or continuous bladder irrigation (CBI), which helps prevent the ormation o any blood clots that may obstruct the out ow o urine, and helps to quell the bleeding. Urine return that is light-red to pink in color indicates that the current rate o irrigation is likely suf cient to prevent clot ormation. The lumen o the three-way catheter may become obstructed due to the relatively small size. Any obstruction in the catheter may lead to excessive urine retention and ultimately bladder wall per oration. I CBI is utilized, it should be gravity ed only and never connected to an intravenous pump. I there is any obstruction to the ow o CBI, the catheter should be ushed (by hand) with 60 to 120 mL o saline to remove any blood clots or debris. This is best per ormed by repeatedly instilling saline with a catheter-tip syringe and withdrawing the uid present in the bladder, until the majority o clot material is extracted. The nursing sta should monitor the amount o irrigation and return, to accurately calculate urine output, and should replace the irrigation bag as soon as it is nearly empty. Similarly, the drainage bags can ll up quickly, and need to be emptied requently so that CBI ow is not reduced (any lull in CBI ow may lead to clot ormation). I a clot orms, it needs to be manually extracted be ore resuming CBI. These patients are at risk or bladder wall per oration, as the wall may be signi cantly weakened a ter endourologic procedures, and stretched thin i intravesical pressures are high rom obstructed CBI. The use o CBI is contraindicated in patients with con rmed or assumed bladder per oration. CBI should also be avoided or used with extreme caution in patients with resh anastomoses o the GU tract. All patients will have some bleeding a ter a transurethral resection o the prostate (TURP) and are managed postoperatively with a three-way catheter and CBI. The source o bleeding is generally rom the venous sinuses o the prostate, so the catheter balloon is in ated to larger volumes than normal (30 mL vs the standard 10 mL) to ll and compress the prostatic ossa or de ect le t by the TURP. In cases with excessive bleeding, the catheter may be put on

■ URETHRAL-VESICAL ANASTOMOTIC LEAK IN RADICAL PROSTATECTOMY Urethral-vesical anastomotic leak (UVAL) is one o the most common postoperative complications in radical prostatectomy. UVAL usually occurs early, with the incidence highest in the rst 7 to 10 postoperative days. UVAL occurs in 1% to 10% o laparoscopic cases and 2% to 10% o radical retropubic prostatectomy cases. Robotic-assisted laparoscopic prostatectomy has advantages over pure laparoscopic techniques due to better visualization o the surgical eld and the ability to per orm a running anastomosis. The majority o anastomotic leaks are located in the posterior segment o the anastomosis, which is the site o the initial suture placement. A ter surgery, the patients overall clinical condition and surgical drain output should be monitored. Drain output should signi cantly decrease over the rst 24 to 48 hours; continued high output may indicate an injury to the ureter, and the uid should be sent or a creatinine level. The majority o patients with mild urinary leak will be asymptomatic and the diagnosis is made based on drain output creatinine level (Figure 67-3). I symptomatic, the patient may have signs o peritonitis or paralytic ileus, which may indicate extravasation o urine into the peritoneum.

Mode ra te to la rge dra in output

As s e s s dra in cre a tinine Cre a tinine > 30 mg/dL

Cre a tinine < 30 mg/dL

Apply tra ction to urina ry ca the te r +/– dra in ma nipula tion

Expe cta nt ma na ge me nt

Cre a tinine le ve l pe rs is ts

Cre a tinine le ve l diminis he s

Re trogra de cys togra phy

P rolonge d ca the te riza tion

Cons ult urologis t with findings indica tive of s ignifica nt UVAL or ure te ra l injury

Figure 67 3 Approach to the patient with suspected urethrovesical anastomotic leak.

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Initial management o a urine leak is conservative; the surgical drain and a transurethral catheter are le t in place or a period o time (to aspirate urine rom the anastomosis, and decompress the bladder, respectively). The urologist may apply gentle traction or manipulate the transurethral catheter (correct catheter placement can acilitate healing the anastomosis) and may repeatedly switch the surgical drain rom active to passive drainage (releasing the pressure o the bulb) and slightly withdrawing the drain over time. I the creatinine content o the drain uid persists ollowing manipulation o the catheter and drain, a cystogram is indicated to rule out injury to the bladder and/or determine the severity o UVAL (alternative imaging includes CT cystography or retrograde urethrogram). I a ureteral injury is suspected, the best imaging is a CT scan using delayed images or a retrograde study o the ureter in the operating room. Longer term urine leaks are managed with prolonged catheterization, and urther interventions may include urinary diversion with a suprapubic catheter or nephrostomy tubes, endoscopic evaluation, or ultimately reoperation.

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■ URINE LEAK FOLLOWING PARTIAL NEPHRECTOMY As partial nephrectomies have become the standard o care or excision o smaller renal parenchymal masses, the incidence o postoperative urinary leak has risen, and currently occurs between 0.5% to 21%, and is more common in excisions that remove endophytic masses involving the collecting system o the kidney. Urinary leak ollowing partial nephrectomy may present acutely or as a more insidious process. Early leak is typically due to unrecognized insult to the collecting duct system or a de ect that was not repaired suf ciently; this should be suspected i drain output exceeds 30 to 40 mL/shi t more than 48 hours a ter surgery. I present, the drain uid creatinine will be markedly elevated (relative to the serum creatinine). The suspected leak should be evaluated with a noncontrast CT or sonogram to evaluate the drain placement, ensure the kidney is not obstructed (leading to higher pressures in the collecting system thereby perpetuating the leak), and ensure there is no urinoma present. Delayed urinary leak will present anywhere between 5 and 14 days. The speci c etiology o a delayed urine leak is unclear, but it is hypothesized that most are simply unrecognized early leaks. The patient with a delayed urine leak may present with ever, drain site tenderness, ank pain and/or drainage rom a port site or incision. The suspected leak should be evaluated with CT with IV contrast (with delayed images to uncover any extravasation o contrast) or sonogram (to identi y any perirenal uid collections). Healing o the leak occurs most rapidly when there is maximal kidney drainage; there ore, a percutaneous drain may be required to evacuate an urinoma i it is impeding kidney drainage. In addition, i the bladder has high voiding pressures, the patient may need a short-term (1-3 days) indwelling catheter to reduce those pressures and allow the kidney to drain properly. The patient can be discharged with the drain and/or the Foley in place; they should be instructed to record daily drain volumes and have close ollow-up (within a week) with the surgeon.

■ COMPLICATIONS FOLLOWING ADRENALECTOMY Adrenalectomies are most commonly per ormed or the removal o pheochromocytomas, aldosteronomas, and glucocorticoidproducing tumors, and the physician should be able to recognize the symptoms that arise ollowing abrupt removal o the hormones these tumors produce. Pheochromocytoma, aldosteronoma, and glucocorticoid-producing tumors produce norepinephrine/epinephrine, aldosterone, and cortisol, respectively, which predisposes the patient to a relative de ciency o these hormones. Other complications associated with adrenalectomy include postoperative bleeding or pneumothorax. The proximity o the adrenal glands to 458

the liver, spleen and pancreas, as well as the posterior-in erior border o the diaphragm predispose surgical interventions to problems involving these organs. Patients with a pheochromocytoma are usually on alpha-blockade perioperatively to control hypertension and o ten have contracted blood volumes due to the chronic exposure to catecholamines (and resulting increase in vascular tone). These patients are very vulnerable to the development o perioperative hypotension due to the abrupt decrease in norepinephrine. Aggressive uid resuscitation should be started be ore surgery and continued throughout the procedure; vasopressors may also be required. Hypoglycemia is also a risk, due to a rebound increase in insulin and should be closely monitored. Patients with an aldosteronoma are at increased risk o developing either hyperkalemia or hypokalemia in the perioperative period. Due to the excess preoperative aldosterone production, hypokalemia is more typical. Alternatively, in some patients the renin-angiotensin-adrenal-axis is down-regulated (due to the chronic hypernatremia associated with primary hyperaldosteronism). Thus, renin production by the renal juxtaglomerular apparatus is suppressed. I the contralateral adrenal gland cannot compensate or the abrupt decrease in aldosterone levels, patients may actually develop a temporary hyperkalemia and salt-wasting. There ore, close monitoring o electrolytes and blood pressure is needed, and potassium-sparing diuretics should be immediately discontinued postoperatively. Patients with a glucocorticoid-producing adenoma are at risk or adrenocortical insuf ciency (also known as adrenal crisis). Adrenal crisis symptoms include hypoglycemia, hypotension, ever, nausea, vomiting, abdominal pain, hyponatremia, and hyperkalemia. The symptoms are due to the abrupt decrease in serum glucocorticoids rom surgical removal, as well as the suppression o the contralateral adrenal gland rom negative eedback at the level o the anterior pituitary. Perioperative administration o mineralocorticoids and glucocorticoids can prevent (or at least attenuate) postoperative adrenal crises. Patients who have undergone bilateral adrenalectomy will require long-term steroid replacement therapy. Patients who have had partial or unilateral adrenalectomy may or may not require supplementation. Due to the anatomy and vascular supply o the adrenal gland, these surgeries have a high risk o hemorrhage; although this is usually recognized intraoperatively, hemodynamic instability shortly a ter surgery should be considered an unrecognized vascular insult until proven otherwise. Signi cant bleeding may require exploration in the operating room and will require the immediate noti cation o the surgeon. Similarly, respiratory dif culties may be related to an unrecognized or increasing pneumothorax, which should be con rmed on chest radiograph. Lastly, pancreatitis can occur rom manipulation or injury to the tail o the pancreas, and should be considered in patients with severe back pain, abdominal pain and inability to tolerate oral intake. This nding may be con rmed with elevated amylase and lipase levels and may require bowel rest with parenteral nutrition.

■ UROLITHIASIS Kidney stones a ect approximately 1/11 US adults at some point during their lives. Any patient with unilateral ank or groin pain, with or without hematuria, should raise the suspicion o urolithiasis, particularly in a patient with prior history o stones or known risk actors (ie, diabetes, obesity, metabolic syndrome, gout, Caucasian ethnicity, dehydration, etc). I an obstructing, symptomatic kidney stone is suspected, imaging should be obtained. Ultrasonography can identi y the presence or absence o hydronephrosis, and can o ten identi y stones as

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Brandes S. Urologic Complications rom Pelvic and Vaginal Surgery: How to Diagnose and Manage. http://urology.wustl.edu/en/ Patient-Care/ ReconstructiveSurgery/ Urologic-Complicationsrom-Surgery. Accessed March 31, 2015.

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Baldini G, Bagry H, Aprikian A, Carli F. Postoperative urinary retention: anesthetic and perioperative considerations. Anesthesiology. 2009;110(5):1139-1157.

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and normal calcium. Urinary citrate is a known stone inhibitor and is in high concentration in lemon and orange juice. Additional dietary and medical intervention, such as urinary alkalinization or thiazide therapy, is dependent on the type o stone as well as the patient’s 24-hour urine collection.

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well, but the sensitivity is poor and is o ten inadequate or surgical planning. A low-dose, noncontrasted CT scan o the abdomen and pelvis (CT IVP) is a sensitive and speci c modality or determining stone size, location and degree o consequent obstruction, i present. Moreover, it can assess a stone’s hardness or composition by noting the Houns eld Units (HU), which measures the radiodensity relative to distilled water at standard temperature and pressure. An abdominal radiograph o the kidney, ureter and bladder (KUB) can be help ul in patients who can be managed conservatively or stone disease. Additionally, i shock wave lithotripsy is desired, a KUB must be obtained to ensure that the stone is visible prior to scheduling. However, not all stones are visible on KUB, and bowel gas and other arti acts can intermittently obscure the image. I in ection or urosepsis is suspected (based on ever, chills, dysuria, unstable vital signs, leukocytosis, or ndings on urinalysis) de nitive stone treatment should be delayed and a ureteral stent or percutaneous nephrostomy tube should be placed to relieve the obstruction and allow or decompression o the collecting system. The stent or nephrostomy tube should be le t in place while the in ection is treated with an appropriate course o antibiotics. A ter resolution o symptoms and a negative urine culture, the patient can undergo de nitive stone treatment. I the stone is small (generally 100 mL

• Tre a t cons tipa tion • Re vie w me dica tions • Cons ide r tria l of a lpha -blocke r (me n) • Ca the te r dra ina ge if P VR 200-500 mL, the n re a s s e s s

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UI as s o c iate d with • P a in • He ma turia not a s s ocia te d with UTI • P e lvic ma s s • P e lvic irra dia tion • P e lvic/LUT s urge ry • P rola ps e be yond hyme n • S us pe cte d fis tula

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Inc lude e valuatio n and tre atme nt in trans itio ns c o mmunic atio n

If ins uffic ie nt impro ve me nt, re as s e s s fo r tre atme nt o f c o ntributing c o mo rbidity, me dic atio ns , func tio nal impairme nt

If c o ntinue d ins uffic ie nt impro ve me nt, o r s e ve re as s o c iate d s ympto ms are pre s e nt, c o ns ide r s pe c ialis t re fe rral as appro priate pe r patie nt pre fe re nc e s and

Figure 71 1 Algorithm for treatment of new or worsening urinary incontinence in hospitalized patient.

genito-urinary tract; anticipated long duration surgery (with catheter removal in postacute care unit); when there is a need or intraoperative urinary output measurement; and when large volume f uids or diuretics are required during surgery. In the postoperative period, catheters should be removed as soon as possible and appropriate toileting and use o bedside devices should be considered. Dementia: Management o UI in patients with dementia in the hospital setting should ocus on potentially reversible actors (see above) and nonpharmacological approaches (containment, prompted voiding, scheduled toileting). Antimuscarinic medications or urge UI should not be started in patients with dementia in the acute care setting because o the likelihood that new or worsening UI is due to “transient” causes, and because o the risk o worsening cognition. Antimuscarinics should not be given to patients taking cholinesterase inhibitors (eg, donepezil); mirabegron can be used instead, i there are no contraindications to its use. Heart failure: Patients with diastolic and systolic heart ailure may develop UI rom new or higher doses o loop (but not thiazide) diuretics, and nocturia rom remobilized lower-extremity edema. There is no speci c evidence-based recommendation regarding timing o diuretics to prevent UI and nocturia in hospitalized patients. Data rom a small, short term randomized trial in nonhospitalized patients showed that oral urosemide 40 mg given 6 hours be ore bedtime had no impact on nocturia episodes but did increase daytime requency. Alteration in positioning and prolonged time supine also a ect diuresis and natriuresis, and patients with CHF likely have other multimorbidity that contributes to incontinence and nocturia. Patients may bene t 486

rom general HF management strategies, such as compression stockings and avoidance o medications causing edema and f uid retention, as well as repeated “n o 1” trials o optimal diuretic timing in individual patients. Catheter insertion to measure urine output should be avoided, especially outside o the critical care setting unless UI poses a signi cant barrier to accurate urine output measurement. End of life: Urinary catheters are appropriate to use in dying patients or com ort, especially to avoid requent changes o protective garments. Neurologic diseases: Adults with complex neurologic diseases (eg, multiple sclerosis, spinal cord injury, Parkinson’s disease, stroke) requently have UI and FI because o direct e ects on areas o the neuroaxis important or bladder and bowel unction (especially pre rontal cortex, pontine and suprapontine areas, and thoracic and lower-lumbar spinal cord), as well as associated cognitive and unctional impairments. These patients should always have PVR checked as part o the evaluation. Consideration o medications and other actors that may contribute to urinary retention is important prior to placing a urinary catheter (Table 71-7). Constipation can be common and contribute to urinary symptoms and FI. Select patients (especially those with high PVR or UI and no external anal sphincter tone at rest or diarrhea with nonin ectious etiology or FI) may need urther evaluation by a specialist in urology, gynecology, gastroenterology, colorectal surgery, or neurology depending on the type o incontinence and potential etiologies. Nurses specializing in Wound, Ostomy, and Continence (WOC) care are also a valuable resource in the acute care setting.

INITIAL INTERVENTION

Anal S phinc te r Impairme nt (S que e ze )

Lo o s e S to o l Co ns is te nc y

• Re gula r toile ting while a wa ke • Cons ide r furthe r e va lua tion with ma nome try (outpa tie nt) or ima ging s tudie s if ne urologic ca us e is s us pe cte d (inpa tie nt)

• Re vie w me dica tions • Re vie w die ta ry inta ke • Cons ide r tria l of Iope ra mide for noninfe ctious dia rrhe a • Tre a t ma la bs orption s yndrome s , if pre s e nt

Hard S to o l Co ns is te nc y

• • • •

C H A P T E R 7 1 I n c o n t i

Multimorbidity Me dica tions De cre a s e d mobility De lirium Nutrition Ga s troe nte ritis Dia rrhe a Cons tipa tion S tool impa ction

• As s e s s , tre a t, a nd re a s s e s s for contributing fa ctors (Ta ble s ) • Ma ximize toile t/commode a cce s s ibility • As s e s s nutritiona l inta ke • S tool s tudie s /culture if othe r GI s ymptoms pre s e nt • Ima ging s tudie s de pe nde nt on s ymptoms a nd phys ica l e xa m findings • Ta rge te d phys ica l e xa m/digita l re cta l e xa mina tion: impa ction, ne w ne urologica l s igns (e g, ca uda e quina ), mobility, a na l s phincte r tone a t re s t a nd with volunta ry contra ction, a nocuta ne ous re fle x (a na l wink)

n

• • • • • • • • •

Pas s ive

e

CLINICAL AS S ES S MENT

Mixe d urg e and pas s ive

n

Urg e nc y

c

HIS TORY/ S YMPTOM AS S ES S MENT

e

Ne w or wors e ning FI in hos pita lize d pa tie nts

FI as s o c iate d with • Blo o d in s to o l and o the r “re d flag ” s ympto ms not a s s ocia te d with ga s troe nte ritis • Impaire d re s ting re c tal to ne • P e lvic/re cta l ma s s • P e lvic irra dia tion • P e lvic/lowe r GI tra ct s urge ry • Re cta l prola ps e • S us pe cte d fis tula

IF UNCERTAIN

Re vie w me dica tions Re vie w die ta ry inta ke Eva lua te for impa ction Tre a t with ora l la xa tive a nd e ne ma s (if indica te d)

ONGOING MANAGEMENT AND REAS S ES S MENT If ins uffic ie nt impro ve me nt, re as s e s s fo r tre atme nt o f c o ntributing c o mo rbidity, me dic atio ns , func tio nal impairme nt Inc lude e valuatio n and tre atme nt in trans itio ns c o mmunic atio n

If c o ntinue d ins uffic ie nt impro ve me nt, o r s e ve re as s o c iate d s ympto ms are pre s e nt, c o ns ide r s pe c ialis t re fe rral as appro priate pe r patie nt pre fe re nc e s and

Figure 71 2 Algorithm for treatment of new or worsening fecal incontinence in hospitalized patients.

PRACTICE POINT Indications or re erral or incontinence include (see also treatment algorithms): • Urology: hematuria without UTI, pelvic mass, prior pelvic radiation, prior pelvic/lower urinary tract surgery, suspected bladder stula • Gynecology: pelvic pain not responding nonpharmacologic and pharmacologic treatments, pelvic mass, prior pelvic radiation, prior pelvic/lower urinary tract surgery, suspected stula, prolapse beyond the hymen • Gastroenterology:“Red f ag”or alarm symptoms (chronic GI bleeding, progressive unintentional weight loss, progressive dysphagia, nocturnal symptoms, iron de ciency anemia, amily history o colon cancer or inf ammatory bowel disease), acute inf ammatory bowel disease, pancreatitis, malabsorption syndromes, stool impaction not responding to pharmacologic treatment and enemas • Colorectal surgery: rectal mass, colon cancer, congenital abnormalities, inability to reduce rectal prolapse

• •

Neurology: cauda equina or tumor, spinal cord injury, multiple sclerosis, stroke, prior back surgery with other neurologic ndings Nurses specializing in Wound, Ostomy, and Continence (WOC): incontinence associated dermatitis, pressure wounds, management in spinal cord injury, special containment requests

URINARY RETENTION

■ PATHOPHYSIOLOGY Urinary retention (UR) may be acute or chronic, and partial (patient may still void or leak urine) or complete (inability to void). Acute UR presents with a relatively sudden di culty or inability to pass urine, usually with abdominal or suprapubic pain. Pain may be absent due to impaired sensory a erents (eg, with cauda equina syndrome), medication (eg, narcotics), or not recognized (eg, cognitive impairment). Chronic retention may be asymptomatic except or associated UI. The causes o UR all into three general categories: increased bladder outf ow resistance (mechanical or dynamic); interruption o 487

TABLE 71-6 Indications for Indwelling Urethral Catheters

I

I

I

T

R

A

P

Indication Acute urinary retention or obstruction

b

a

h

e

R

Accurate measurement o urinary output in critically ill patients

N

d

e

l

l

i

k

S

d

n

a

n

o

i

t

a

t

i

l

i

Perioperative use

e

r

a

C

g

n

i

s

r

u

Stage 2 or greater open sacral or perineal wounds in incontinent patients Com ort care at the end o li e

Management • Remove catheter as soon as possible (eg, a ter reversible causes identi ied and removed) • Arrange appropriate outpatient care ollowing hospitalization • Minimize time with catheter inserted • Remove catheter when alternative means o urinary collection are available • Urologic surgery or other surgery on contiguous structures in the genitourinary tract • Anticipated long duration surgery (with catheter removal in PACU) • Need or intraoperative urinary output measurement • Large volume luids or diuretics during surgery • To improve healing and reduce exposure to moisture

• When goal is to improve quality o

li e or patient and caregivers

Adapted rom the Centers or Disease Control and Prevention: Guidelines or Prevention o Catheter-Associated Urinary Tract In ections 2009. http:// www.cdc.gov/HAI/ca_uti/uti.html. Accessed April 1, 2015.

detrusor sensory a erents or motor e erents; and decreased detrusor contractility (neurogenic, myogenic, or iatrogenic [medications]) (Table 71-7). UR is common a ter spinal or epidural anesthesia. Although prostate enlargement is common in older men and i advanced can cause outlet obstruction and chronic UR, acute UR is usually precipitated by other actors. Outlet obstruction in women is uncommon; when present, it is usually due with prior anti-incontinence surgery or marked pelvic organ prolapse.

■ EVALUATION The evaluation o urinary retention also is similar to that o UI and FI (Table 71-7). Risk actors or elevated PVR, in addition to medications (Table 71-2), include previous history o UR, new stroke, untreated

TABLE 71-7 Common Causes of Urinary Retention in Hospitalized Patients Mechanical Stool impaction Catheter obstruction (eg, blood clot, twisted catheter)

488

Neurogenic Acute cauda equina syndrome Sacral/subsacral spinal cord injury Bedrest Sacral herpes zoster Urinary tract in ection Bladder overdistention rom rapid dieresis

Medications Anesthesia Opiates Anticholinergics (eg, phenergan, metoclopramide, antispasmodics)

UTI, hip racture, ecal impaction, male gender, bedrest, and benign prostatic enlargement. Neither abdominal palpation nor percussion is sensitive or speci c or bladder distension. Only by bladder scan or catheterization accurately determines the presence or absence o UR accurately. I the patient can void, bladder volume should be determined only a ter they void, and the percentage emptying considered as well as the absolute postvoiding residual (PVR) volume. There is no consensus on cut-o values or “normal” PVR either rom the perspective o de nition or clinical relevance. Women may tolerate higher PVRs than men because they have less urethral resistance, and PVR up to 200 mL may not be clinically relevant unless the patient has UTIs, requency, urgency, or UI. In men, PVR > 100 mL are generally considered abnormally elevated. In the absence o new renal impairment men and especially women have a low prior probability o hydronephrosis due to elevated PVR and upper-tract imaging is not necessary. The gold standard or the diagnosis o outlet obstruction is urodynamic pressure-f ow study; cystoscopy alone is nonspeci c and insensitive. Acute UR, prostate in ection, and urethral instrumentation/catheterization may elevate prostate speci c antigen (PSA).

■ MANAGEMENT Figure 71-3 presents a general management approach or patients with suspected acute urinary retention. For acute retention, all patients should have bladder decompression with an indwelling catheter or several days. Antibiotic and antimicrobial catheters are not recommended or short-term hospital usage due to the relative lack o e cacy, as well as patient discom ort and cost. Following catheter insertion, patients should be treated or potentially remediable causes such as medications, and impaction. Medications may expedite catheter removal in selected patients. Alpha-adrenergic antagonists (eg, terazosin, doxazosin, tamsulosin, al uzosin) can be used or UR due to prostatic obstruction. 5-Alpha reductase inhibitors ( nasteride and dutasteride) are not use ul in the acute care setting because o the delayed onset o treatment e ect (up to 6 months). Methylnaltrexone (0.15 mg/kg o body weight) may be used or opioid-induced and possibly postoperative urinary retention. Bethanecol chloride is ine ective. A voiding trial without catheter should ollow decompression. With the patient adequately hydrated, the catheter is removed (never clamped), and a PVR checked a ter the rst void (or bladder volume checked i there is no void a ter about 6 hours). I the PVR is 60% o all pressure ulcers occur at these locations. 492

■ SKIN CARE The skin o patients at risk o pressure ulceration should be inspected regularly or erythema. This includes pressure points, as well as areas o contact with medical devices, such as catheters, oxygen tubing, ventilator tubing, and semirigid cervical collars, as these may also cause ulceration. Pain over an erythematous area may herald skin breakdown. It is not always possible to see redness on darkly pigmented skin. Depending on the degree o pigmentation, erythema may appear blue or purple, compared to adjacent skin. Erythema should be categorized as blanching or nonblanching. Localized heat, edema, and induration over pressure points are additional warning signs or pressure ulcer development. Patients may need more requent inspection in response to any deterioration in condition.

■ SUPPORT SURFACES Pressure should be distributed as evenly as possible across the patient’s body to reduce the incidence o pressure ulcers. The use o support sur aces may assist in pressure redistribution. The Centers or Medicare and Medicaid Services have divided support sur aces into three categories or reimbursement purposes. Group 1 devices are static and do not require electricity. Static devices include air, oam, gel, and water overlays or mattresses. These devices are ideal when a patient is at low risk or pressure ulcer development. The devices have some drawbacks: oam may degrade and lose its sti ness over time, and gel mattresses can increase skin heat and moisture. Group 2 devices are dynamic and powered by electricity or pump action. These devices include alternating and low-air-loss mattresses. These mattresses are better or patients at moderate to high risk or pressure ulcers, or who have ull-thickness pressure ulcers (Stage III and Stage IV). Critically ill patients are excellent candidates or this group o support sur aces. Group 3 devices, also dynamic, comprise only air- uidized beds. These are electric, and contain silicone-coated beads that lique y when air is pumped through the bed. These beds are used or patients at very high risk or pressure ulcers, patients with nonhealing ull-thickness pressure ulcers, and patients with numerous truncal ull-thickness pressure ulcers. The National Pressure Ulcer Advisory Panel has suggested new de nitions or support sur aces that move away rom these categories and divide support sur aces into simply powered or nonpowered. Approximately 20% o all pressure ulcers are ound on the heels. Heel-protection devices should be considered or hospitalized patients at risk or pressure ulcers. The heels should be elevated and of oaded to distribute the weight o the leg along the cal without putting pressure on the Achilles tendon. The knee should also be in slight exion to avoid hyperextension o the knee, which could lead to obstruction o the popliteal vein and deep vein thrombosis. Some hospitals may alternatively use a pillow to oat the heels. I the use o a pillow is pre erred, then the pillow should be placed under the calves to elevate the heels rom the mattress.

C H A P T E R 7 2 P r e s s u r e U l

When a pressure ulcer develops, the hospitalist must provide local care o the ulcer, but also assess the patient’s overall physical health, nutritional status, pain level, and psychosocial health, considering the whole patient, not merely the ulcer. In addition to mechanical loading and support sur aces, as discussed above, pressure ulcer management includes the ollowing.

c

TREATMENT

e

Decreasing mechanical load and pressure exposure are crucial in preventing pressure ulcers. High pressures over bony prominences or short periods o time and low pressures over bony prominences or long periods o time are equally damaging. Repositioning requency should be determined by the patient’s skin condition and tissue tolerance, level o activity and mobility, general medical condition, overall treatment objectives, and support sur aces applied to the bed or chair. Turning and repositioning hospitalized patients every 2 hours while in bed, and every hour while seated, is reasonable or most hospitalized patients. Those who are critically ill may require hourly repositioning, while stable patients on specialty beds, such as low air loss or air uidized, may only need repositioning every 4 hours. The patient should be repositioned to relieve or redistribute pressure. Trans er aids that reduce riction and shear orces, such as the Hoyer li t or trapeze, should be used. Avoid positioning the patient directly on a bony prominence or directly onto medical devices, such as tubes or drains. The 30°-tilt position and the standard 90° side-lying position seem to be equivalent in protection against the development o pressure ulcers.

While nutritional status in patients with pressure ulcers is o ten poor, the evidence or a relationship between nutrition intake and pressure ulcer prevention is not always supported by randomized controlled trials. There is also a lack o empirical evidence to link the use o vitamin and mineral supplementation to the prevention o pressure ulcers. There ore, while nutritional status should be optimized in patients at risk or pressure ulcers, overtreatment should also be avoided.

r

■ MECHANICAL LOADING

■ NUTRITION

s

Protecting skin rom excessive moisture with barrier paste or other products is essential, as moisture and warmth impair the mechanical integrity o the stratum corneum. Massaging areas o reddened skin should be avoided, as these may contain damaged blood vessels or ragile skin. Skin emollients to hydrate dry skin should be considered.

■ ULCER ASSESSMENT The ulcer bed should rst be cleansed with a nontoxic solution. Cleaning removes necrotic debris and bacteria that may delay healing. Normal saline (0.9% sodium chloride) or water solutions are best, as neither is toxic to healthy tissue. Although the active ingredients in newer wound cleansers may be nontoxic sur actants, the inert carrier may be toxic to healthy granulation tissue. The pressure ulcer should be assessed or location, stage, size (length, width, and depth), sinus tracts, undermining, tunneling, exudate (quality and quantity), necrotic tissue, and the presence or absence o granulation tissue and epithelialization. This comprehensive assessment establishes the baseline or measuring ulcer healing or deterioration. Ulcer assessment should be done at least weekly.

■ STAGING Upon completing the pressure ulcer assessment, the ulcer should be staged. The most commonly used pressure ulcer staging system was developed by the National Pressure Ulcer Advisory Panel. Their system classi es skin changes into ve levels o skin ulceration (Table 72-1 and Figure 72-2). This system rates the pressure ulcer rom super cial tissue damage (Stage I) to ull-thickness skin loss involving muscle or bone (Stage IV) and deep tissue injury. I the pressure ulcer is covered with necrotic tissue (eschar), it is noted as unstageable.

■ WOUND BED PREPARATION A recent concept in the healing o chronic ulcers is wound bed preparation. The goal o wound bed preparation is to provide the ulcer with an optimal environment or healing: a wound bed that is highly vascularized, with minimal exudate. The three main principles are debridement, bacterial balance, and exudate control. There is no optimal debridement method. The pre erred method is determined by the goals o the patient, the presence or absence o in ection, the amount o dead tissue present, and cost considerations. There are ve common types o debridement: mechanical, autolytic, enzymatic, sharp, and biosurgery. Mechanical debridement uses wet-to-dry gauze to adhere to the necrotic tissue, which is then removed. Removal o the gauze dressing also removes necrotic tissue and wound debris. The challenge with mechanical debridement is the possibility that healthy granulation tissue may also be removed along with devitalized tissue, thus delaying wound healing. Autolytic debridement involves semiocclusive, transparent lm dressings, and occlusive dressings, such as hydrocolloids and hydrogels, which create a avorable environment or the body’s enzymes to break down the necrotic tissue. Enzymatic 493

Pressure Ulcer Stage Deep tissue injury

Definition Purple or maroon localized area o discolored intact skin or blood- illed blister due to damage o underlying so t tissue rom pressure and/or shear

Stage I

Intact skin with nonblanchable redness o a localized area, usually over a bony prominence

Stage II

Partial thickness loss o dermis presenting as a shallow open ulcer with a red, pink wound bed without slough. May also present as an intact or open/ruptured serum- illed blister Full-thickness tissue loss. Subcutaneous at may be visible, but bone, tendon, or muscle are not exposed. Slough may be present but does not obscure the depth o tissue loss. May include undermining and tunneling

S

d

n

a

n

o

i

t

a

t

i

l

i

b

a

h

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R

I

I

I

T

R

A

P

TABLE 72-1 National Pressure Ulcer Staging System

g

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s

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N

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l

l

i

k

Stage III

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a

C

Stage IV

Full thickness tissue loss with exposed bone, tendon, or muscle. Slough or eschar may be present on some parts o the wound bed. Often includes undermining and tunneling

Description • The area may be preceded by tissue that is pain ul, irm, mushy, boggy, warmer, or cooler, as compared to adjacent tissue • Deep tissue injury may be di icult to detect in individuals with dark skin tones • The area may rapidly evolve to expose additional layers o tissue, even with optimal treatment • The area may be pain ul, irm, so t, warmer, or cooler, as compared to adjacent tissue • Stage I may be di icult to detect in individuals with dark skin tones Presents as a shiny or dry shallow ulcer without slough or bruising. This stage should not be used to describe skin tears, tape burns, perineal dermatitis, maceration, or excoriation

• The depth o a Stage III pressure ulcer varies by anatomical

• •

•

•

Unstageable

Full thickness tissue loss in which actual • depth o the ulcer is completely obscured by slough (yellow, tan, gray, green, or brown) and/or eschar (tan, brown, or black) in the wound bed

debridement employs proteolytic enzymes, such as papain-urea, collagenase, and trypsin, to remove necrotic tissue. While enzymatic debridement is e ective, it is slower than other types and o ten costly. Sharp debridement with scalpel or laser is probably the most rapid and e ective type o debridement, and should be strongly considered when the patient is suspected o having cellulitis or sepsis. Finally, biosurgery (maggot therapy) is another e ective and relatively quick method o debridement. Maggot therapy is very speci c or devitalized tissue, although patient and provider unease have limited its acceptance. Managing bacterial burden is an important consideration in wound bed preparation. All pressure ulcers contain a variety o bacteria. Bacteria are more likely to impede wound healing when their concentration exceeds 106 organisms per gram in the ulcer. Certain bacteria may impair ulcer healing at lower concentrations. Signs o ulcer in ection include odor, purulent exudate, excessive draining, bleeding, and pain. I these are present, wound cultures should be obtained, and treatment with oral or intravenous antibiotics should be considered based on antimicrobial sensitivity testing. Other strategies to reduce bacterial bioburden include the use o silver impregnated dressings and topical sul a silverdiazine. Exudate management is the last component o wound bed preparation. Excessive exudate decreases ulcer healing, and may damage healthy surrounding tissue. Exudates are managed by 494

location. The bridge o the nose, ear, occiput, and malleolus do not have subcutaneous tissue, and Stage III ulcers can be shallow. In contrast, areas o signi icant adiposity can develop in extremely deep Stage III pressure ulcers Bone/tendon is not visible or directly palpable The depth o a Stage IVpressure ulcer varies by anatomical location. The bridge o the nose, ear, occiput, and malleolus do not have subcutaneous tissue, and these ulcers can be shallow Stage IVulcers can extend into muscle and/or supporting structures (eg, ascia, tendon, or joint capsule), making osteomyelitis likely to occur Exposed bone/tendon is visible or directly palpable Until enough slough and/or eschar is removed to expose the base o the wound, the true depth, and there ore stage, cannot be determined. Stable (dry, or adherent, intact without erythema or luctuance) eschar on the heels serves as the body’s natural biological cover and should not be removed

selecting an appropriate dressing. Dressings can be classi ed as gauze, petroleum-based nonadherent gauze, transparent lms, hydrocolloids, oam islands, alginates, hydrogels, composites, and combinations (Table 72-2). Whichever dressing is selected, the pressure ulcer should be kept moist to optimize healing. Since no studies exist that demonstrate that one dressing heals all pressure ulcers within an ulcer classi cation, a care ul assessment o the pressure ulcer, patient needs, and environmental actors ( requency o dressing changes to increase adherence) must be considered. Since wet-to-dry gauze dressings are a orm o debridement, they should only be used in necrotic wounds. Once healthy granulation tissue is observed, wet-to-dry dressing should be stopped, and other dressings should be used. Negative pressure therapy, or vacuumassisted closure (VAC) therapy, should also be considered or exudative ulcers. Negative pressure therapy removes excess exudate, increases local blood ow, and promotes granulation tissue. Negative pressure therapy should not be used in pressure ulcers with suspected osteomyelitis, eschar, or exposed blood vessels or viscera.

■ NUTRITION Many patients with pressure ulcers are malnourished. High-protein diets in poorly nourished patients with pressure wounds are reasonable, although there is a paucity o evidence to support their use.

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Epide rmis

2

7

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E

De rmis

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Adipos e tis s ue

S ta ge I

D

S ta ge Ill

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Bone

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Mus cle

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E

S ta ge Il

S ta ge IV

F

S us pe cte d de e p tis s ue injury

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Uns ta ge a ble

Figure 72 2 National pressure ulcer staging system. (A) Normal skin. (B) Stage I pressure ulcer. (C) Stage II pressure ulcer. (D) Stage III pressure ulcer. (E) Stage IVpressure ulcer. (F) Deep tissue injury. (G) Unstageable pressure ulcer. (Reproduced with permission rom the National Pressure Ulcer Advisory Panel, 2011.)

■ PAIN MANAGEMENT Pressure ulcers are o ten pain ul, especially Stage IVulcers. Strategies to reduce pain include the use o dressings that may mitigate pain, such as those containing so t-silicone, and administering analgesic prior to dressing changes.

■ MONITORING HEALING There is considerable debate regarding the use o reverse staging o pressure ulcers to monitor healing. Staging o pressure ulcers is only

appropriate or de ning the maximum anatomic depth o tissue damage. Since pressure ulcers heal to progressively more shallow depth, they do not replace lost muscle, subcutaneous at, or dermis be ore they reepithelialize. Instead, pressure ulcers are lled with granulation (scar) tissue composed primarily o endothelial cells, broblasts, collagen, and extra cellular matrix. Thus, a Stage IV pressure ulcer cannot become a Stage III, Stage II, or subsequently Stage I. When a Stage IVpressure ulcer has healed, it should be classi ed as a healed Stage IVpressure ulcer, not a Stage 0. There ore, reverse staging does not accurately characterize what is physiologically occurring in the pressure ulcer. 495

P

TABLE 72-2 Pressure Ulcer Dressing Classification Selection Partial Thickness (Stages I and II) X X X (Stage II only) X (Stage II only) X (Stage II only) X (Stage II with dry wound bed only)

Full Thickness (Stages III and IV) X (As a secondary dressing) X X X X (Dry wound beds only) X X

Heavy Drainage

X X X

X X X X

X

X X

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T

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Dressing Classification Transparent ilms Hydrocolloids Alginates Foams Composites Hydrogels Hydro ibers Antirecalcitrant dressings

Moderate Drainage

n

i

s

r

u

N

d

e

l

l

i

k

S

d

The Pressure Ulcer Scale or Healing (PUSH) and the Bates-Jensen Wound Assessment Tool (BWAT) are both valid and reliable or measuring pressure ulcer healing. The PUSH tool requires less time, having only three items, compared to the 13 items o the BWAT tool. For both tools, a lower score indicates a greater degree o healing. Both tools are usually used weekly.

C

g

■ ADJUNCTIVE THERAPY

e

r

a

When the pressure ulcer is not showing signs o healing within 2 to 4 weeks, adjunctive therapies should be considered. The most commonly adjunctive therapies include electrical stimulation, hyperbaric oxygen, growth actors, and autologous skin. Electrical stimulation is the use o electrical current to stimulate cellular processes important to pressure ulcer healing. These processes include increasing broblasts, neutrophils, and macrophages, collagen and DNA synthesis, and increasing the number o receptor sites or speci c growth actors. Electrical stimulation is most e ective in healing Stage III and IVpressure ulcers. Hyperbaric oxygen is believed to promote wound healing by stimulating broblast, collagen synthesis, epithelialization, and control o in ection. However, there remains a dearth o studies investigating the association o hyperbaric oxygen and healing pressure ulcers. The use o growth actors and skin equivalents in healing o pressure ulcers is relatively new. The use o cytokine growth actors, such as recombinant platelet-derived growth actor-BB (rhPDGF-BB) and broblast growth actors (bFGF), and skin equivalents are currently under study. Further research is needed to identi y the appropriate ulcer environment or growth actors to be optimally e ective.

PRACTICE POINT

•

496

All wounds may be pain ul, and they may become more sensitive over time. Light touch or even air movement across a pressure ulcer may be exquisitely pain ul or some patients. Control o background pain and incident pain (pain with dressing changes) may require basal pain medication, as well as premedication or dressing changes. Nonpharmacologic measures that may reduce patient discom ort during dressing changes include measures that make the environment less stress ul, such as noise reduction, engaging amily members and ancillary personnel in hand holding when appropriate, requent explanation and verbal engagement with the patient, and limiting wound manipulation and exposure to the minimum necessary.

DISCHARGE CHECKLIST □ Have the patient and outpatient caregivers been given clear instructions on wound care, turning, and positioning? □ Do outpatient caregivers have appropriate support sur aces, trans er devices, and wound dressings or the patient? □ Has the patient’s nutritional status been optimized? Are additional measures necessary or nutritional support in the outpatient setting? □ Has outpatient ollow-up been arranged with wound clinic, in ectious diseases, and plastic surgery, as appropriate?

SUGGESTED READINGS Ayello EA, Braden B. How and why to do pressure ulcer risk assessment. Adv Skin Wound Care. 2002;15:125-132. Bolton LL, van Rijswijk L, Sha er FA. Quality wound care equals cost-e ective wound care: a clinical model. Adv Skin Wound Care. 1997;10(4):33-38. Lyder C, Grady J, Mathur D, et al. Preventing pressure ulcers in Connecticut hospitals using the plan-do-study-act model or quality improvement. Jt Comm J Qual Patient Saf. 2004;30:205-214. Lyder CH, Preston J, Grady J, et al. Quality o care or hospitalized Medicare patients at risk or pressure ulcers. Arch Intern Med. 2001;161:1549-1554. National Institute or Health and Clinical Excellence. The Prevention and Management of Pressure Ulcers in Primary and Secondary Care. London: National Institute or Health and Care Excellence (UK); 2014. http://www.ncbi.nlm.nih.gov/pubmedhealth/ PMH0068960/pd /PubMedHealth_PMH0068960.pd . Accessed September 12, 2016. National Pressure Ulcer Advisory Panel, European Pressure Ulcer Advisory Panel and Pan Paci c Pressure Injury Alliance. In: Haesler E, ed. Prevention and Treatment of Pressure Ulcers: Quick Reference Guide. Perth, Australia:Cambridge Media;2014. http://www.npuap. org/ wp-content/ uploads/ 2014/ 08/ Updated-10-16-14-QuickRe erence-Guide-DIGITAL-NPUAP-EPUAP-PPPIA-16Oct2014.pd . Accessed September 12, 2016. Reddy M, Gill SS, Rochon PA. Preventing pressure ulcers: a systematic review. JAMA. 2006;296:974-984.

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CHAP TER

Patient Safety and Quality Improvement in Postacute Care Mousumi Sircar, MD Jatin K. Dave, MD Matthew L. Russell, MD Helen Chen, MD

Key Clinical Questions 1

Is each medication indicated or either an acute or chronic medical indication?

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I the drug does not have an indication or either an acute or chronic condition, was it prescribed to treat an adverse e ect o another medication?

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Is the patient near the end o li e?

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I you plan to discontinue a medication, does the drug require tapering rather than abrupt discontinuation?

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Are all underlying medical problems optimally treated with drug therapy according to established guidelines?

INTRODUCTION Review o patient sa ety issues and opportunities or quality improvement in skilled nursing acilities (SNFs) begins with the index hospitalization and the necessary steps to guarantee a sa e transition rom the re erring hospital to the receiving acility. The transition o care rom hospitalization to postacute care presents a signi cant risk to the sa ety o the older adult patient. Two key areas that require the clinician’s attention to ensure a sa e transition o care are e ective discharge communication including the discharge summary and the discharge medication reconciliation process. Sa e and e ective transitions reduce preventable readmissions and other adverse events. PREVENTABLE READMISSIONS The costs associated with the current transitions system illustrate the danger o care transitions and the need or a coordinated e ort to ensure patient sa ety. Readmissions rom skilled nursing acilities to the hospital increased by 29% rom 2000 to 2006. Up to 24% o Medicare bene ciaries were readmitted to the hospital rom a skilled nursing acility within 30 days at a cost o $4.34 billion in 2006. Onethird o these occurred within just a week o initial discharge. Older adults are at higher risk or readmission rom skilled nursing acilities and more requently experience care transitions. Patients who are rail or cognitively impaired o ten cannot actively participate in their transition processes and critical in ormation (such as prehospital admission medications that were held) may be lost as a result. Skilled nursing acilities are increasingly being held accountable or preventable readmissions. Similar to hospital metrics, Center or Medicare & Medicaid Services (CMS) is planning to use the 30-day readmission metric as a quality measure or skilled nursing acilities that provide postacute care (PAC). It is there ore important or individual clinicians to have a clear understanding o the PAC capabilities o their community SNFs. Clinicians and health care systems are creating pre erred SNF networks based on readmission rate, length o stay, and other quality measures. Provider groups and hospitals are increasingly partnering with SNFs in quality improvement initiatives that help to ensure patient sa ety and reduce unnecessary utilization and readmissions. PRETRANSFER CONSIDERATIONS IN THE SELECTION OF A SKILLED NURSING FACILITY

■ STAFFING Nurse and medical sta ng ratios can be quite variable across acilities. Re erring clinicians should be mind ul that while the acuity level o PAC admissions has increased, nurse sta ng ratios continue to remain ar lower than those o acute care hospitals. Some nursing homes employ physicians and mid-level sta while others rely on as needed medical coverage rom attending physicians in practice or whom “SNF rounding” is an additional responsibility, and who may not have special expertise in managing postacute care patients. Many postacute care transitions occur a ter hours or on weekends. Facilities with decreased a ter-hour sta ng and coverage may not be ideal receiving acilities or highly medically complex patients. It is important or re erring clinicians to understand and con rm what is reasonably available in these acilities to ensure that sa er transitions can be supported (Table 73-1).

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TABLE 73-1 Basic Considerations When Selecting a Skilled Nursing Facility

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1. How many hours per day/week are physicians and mid-level clinicians on-site? 2. What is the a ter-hours sta ing and coverage? 3. What is the acility’s capacity to per orm diagnostic testing? 4. Is there an on-site pharmacy or do medications need to be delivered rom an o -site vendor? 5. What disciplines are available at the acility? 6. What quality data can be obtained rom the acility? Do they have the capacity to respond to clinical quality o care concerns? 7. Are all readmissions to acute care hospitals regularly reviewed using a standardized tool such as INTERACT to identi y root causes rom preventable readmissions?

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■ LOGISTICS OF PATIENT TRANSFER

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Logistical aspects o patient trans er must be accounted or to ensure a sa e transition. I the patient is trans erred very late in the day or on the weekend, the clinician primarily responsible or the patient may not be available, and there ore an on-call physician may not receive critical in ormation about the patient. This is particularly true or the high-risk patient who is cognitively impaired or delirious or whom a simple trans er to another site o care may cause decompensation. Nurse sta ng also decreases at this time, which may slow the trans er rom the receiving end. Late day trans ers may occur near shi t changes that create yet another transition o care or the patient as clinicians are changed. To minimize this, the patient should be trans erred as early in the day as possible.

■ DIAGNOSTIC TESTING AND OTHER SERVICES At baseline, postacute care skilled nursing acilities provide skilled nursing, rehabilitation therapies, and medical oversight. In some communities, some SNFs are di erentiating themselves by o ering advanced services such as in-house diagnostic testing, palliative care services, or specialty cardiac, pulmonary, or other condition speci c medical care, as well as the ability to manage intravenous medications and other in usions.

TABLE 73-2 Handoff Process Identi y high-risk patients Complete discharge summary using joint commission requirements Ensure sa e medication reconciliation Use step-wise approach (Project RED, Project BOOST) to provide sa e transition or high-risk patients

Standardizing the hando using evidence-based models such as RED (Re-Engineered Discharge) and Project BOOST (Better Outcomes or Older adults through Sa e Transitions) is shown to reduce avoidable readmissions (Tables 73-3, 73-4, and 73-5).

■ THE DISCHARGE SUMMARY The Joint Commission has recommended guidelines or discharge summaries including diagnosis (admission and discharge), key physical examination ndings, key test results, discharge medications, ollow-up appointments, patient and amily education provided, and tasks to be completed. As anticoagulation is a speci c high-risk intervention that can lead to adverse outcomes, it is particularly important to clearly communicate to community or PAC clinicians the goals or anticoagulation, current and recent INR levels (when appropriate), and current anticoagulants in use. Clear language should be utilized on the summary, and any barriers in language or cognition should be elicited such that a translator in the ormer case and a caregiver in the latter may be made available. In addition, baseline and discharge mental status assessment should be clearly communicated so that receiving clinicians will be able to e ectively assess or delirium or other changes in mental status. Red f ags in terms o signs and symptoms should be elucidated such that the patient or clinician will know when rehospitalization may be required. Goals o care discussions should occur to ensure that the level o postacute care that has been chosen is consistent with the patient’s sel -de ned quality o li e. Should a Physician Order or Li e-Sustaining Treatment orm be available in the state, it should be utilized and transmitted to the PAC clinician to clari y resuscitation measures or the patient across all settings. MEDICATIONS

THE DISCHARGE PROCESS Inconsistencies with medications and ollow-up care result in adverse health outcomes. Barriers to sa e transitions include lack o standardization o the discharge process across institutions (o ten hindered by lack o nancial incentive and ragmentation o communication). In addition, electronic medical records requently cause data overload with multiple medication lists on admission and discharge. Transitions o care contribute to this problem through di erences in medication lists that are not requently explained in documentation.

■ MULTIDISCIPLINARY TEAMS Daily interdisciplinary rounds at the hospital with care ul planning o discharge with timely discharge summary and insurance authorization as well as warm hando i necessary can minimize errors and last minute trans er issues. Interdisciplinary teamwork between social work, physicians, and nursing may accelerate the discharge to earlier in the day.

■ INTENSITY OF HANDOFF Clinicians should pursue a more thorough hando based on risks. (Table 73-2). 498

■ MEDICATION RECONCILIATION FAILURES The Joint Commission US Pharmacopeia Medmarx reporting program or medication reconciliation ailures noted 2022 medication

TABLE 73-3 Re-engineered Discharge 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12.

Identi y language barriers Make ollow-up appointments Plan or ollow-up o inpatient tests Arrange outpatient services and equipment (eg, home oxygen) Medication reconciliation with patient Compare treatment plan with national guidelines Teach patient using a written treatment plan Educate patient regarding diagnosis and medications Educate patient about what to do i a problem arises Assess patient’s understanding o plan Send discharge summary to receiving physician Provide telephone support or patient

1. Develop the current list by ensuring preadmission list is correct. 2. Develop updated list. 3. Compare the two lists.

Safe Transition • Education o patient and amily • Coordination among health care pro essionals with timely exchange o in ormation about complex care needs with a warm hando or high-risk transitions • Goals o care/clinical status • Logistical arrangements

Unsafe Transition Complex, chronic conditions requiring multiple clinicians Absence o in ormation speci ying names o consultants, contact in ormation, ollow-up plans

Each clinician works alone lacking knowledge o : - Problems addressed - Services provided - In ormation obtained - Medicines prescribed (discrepancies may result)

C H A P T E R 7 3 P a t i e n t S a e t y I m p r o v e m e n t i n P o s t a c u t e C

• Cumbersome or di cult process o trans erring or harmonizing • •

TABLE 73-5 The Transition of Care from Hospital to Skilled Nursing Facility

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The current list, including immunization and allergies, should be shared with patients, nursing, and pharmacy. The reconciliation is required at all inter aces o care and patient should be guided in creating a personal/portable medication list with stop dates i appropriate. Prior to transition, it is essential to ensure that the acility, home care clinician or caregiver/patient is able to administer the planned medication in the new care setting. Orders such as IV diuretics may be essential in preventing rehospitalization but require sta /caregiver education and may not be available at all sites o care. Improving transitions requires understanding common barriers to a sa e reconciliation process and developing strategies to overcome them. Common barriers include:

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reconciliation errors, 66% occurring during change in level o care, 22% during admission to acility, and 12% discharge. Improper dose/ quantity or omission o medications represented the majority o ailures. In response, the Joint Commission in 2004 designated medication reconciliation as national patient sa ety goal, and in 2005, began requiring accredited organizations to develop and test a designated process or medication reconciliation. Despite these e orts, a 2012 article cited that medication discrepancies occur in up to 70% o patients at admission or discharge, and one-third o these have potential to harm the patient. Actual adverse drug events occur in up to 12% to 17% o patients postdischarge. In 2006, Joint Commission advised the ollowing as a process or medication reconciliation, which was de ned as the process o comparing current medication orders to all medications the patient has been taking. This is expected to occur during any transition in setting, service, practitioner, or level o care. The requirement is represented by a ve-step process.

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CHAMP (Collaboration or Homecare Advances in Management and Practice)

1. Identi ies patients at high risk o rehospitalization 2. Targets speci ic interventions to mitigate potential adverse events 3. Improves low o in ormation between hospital and outpatient physicians and clinicians 4. Improves communication between clinicians and patients Originally developed or home care o the geriatric patient, the CHAMP website now eatures a Care Transitions toolkit with 1. Validated tools to identi y patients at risk or an unsa e transition 2. Intervention tools or patient sa ety 3. Tools or patients and caregivers 4. Tools to improve communication between clinician, patient, and caregivers In 2011, the Center or Medicare &Medicaid Services (CMS) began unding or acute-care hospitals with high readmission rates which partner with community-based organizations providing transition services to improve patient’s transition rom the acute to long-term settings. Application requirements or the Community-based Care Transition Program (CCTP) are described in detail on the CMS webpage

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TABLE 73-4 Start-to-Finish Guidelines for the Discharge Process That Have Been Published

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in ormation within the permanent medications record Lack o clinician reimbursement or completing the medication reconciliation Failure to assign responsibility or signing o on the reconciliation tool to one clinician Failure to assign responsibility to complete list and pass document rom one clinician on to the next clinician Di cult process o trans erring in ormation rom the medication reconciliation tool at the clinician’s level to the patient’s personal medication list

The reimbursement and implementation o Transitional Care Management Visits o ers an opportunity to improve medication reconciliation a ter discharge.

■ PHARMACOKINETIC CHANGES WITH AGING Pharmacokinetic changes with aging, which o ten increases hal -li e o many drugs (Table 73-6). Five classes o medications in which discrepancies can be particularly hazardous and common include anticoagulants, diuretics, ACE inhibitors, lipid-lowering agents, and proton-pump inhibitors.

■ POLYPHARMACY AND UNNECESSARY DRUGS Few studies have measured the prevalence o unnecessary drug use in the elderly population and only one study has evaluated the prevalence o unnecessary drug use speci cally in the inpatient setting. That study reported in a population o 384 rail hospitalized 499

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TABLE 73-6 Pharmacokinetic Changes Leading to Adverse Effects

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Fat Total body water (TBW)

Changes Associated with Aging ↓ First-pass metabolism ↓ Renal clearance o drugs • Serum creatinine unreliable • Cockcro t-Gault ormula required or reliable prediction o renal unction ↑ Distribution o lipophilic drugs due to ↑ at ↓ Distribution o water-soluble drugs due to ↓ TBW

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veterans aged 65 and older, 44% o patients had at least one unnecessary drug at time o discharge rom the hospital. The reasons or a medication to be classi ed as unnecessary included lack o indication (33%), lack o e cacy (19%), and therapeutic duplication (8%). This study also noted that approximately 75% o those receiving an unnecessary drug were prescribed that medication prior to admission while the remaining 25% had an unnecessary drug started during hospitalization.

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On admission, throughout hospitalization, and with any transition o care:

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Determine whether drug side e ects are responsible or any new symptoms or exacerbating underlying medical conditions. Establish clear and practical therapeutic goals and monitoring plans. Review periodically medications and per orm drug reconciliation with each transition, including screen or adverse drug reactions, therapeutic ailures, and adverse drug withdrawal events. Taper or discontinue ine ective or redundant or possibly harm ul medications. Minimize adverse e ects by screening or drug-drug and drug-disease interactions be ore prescribing a medication to a patient. Develop expertise in prescribing a ew select drugs—the medication’s dosing, therapeutic and adverse e ects—to manage common problems in the elderly. When in doubt, consult with a pharmacist. In older patients, i starting a new medication, start low and gradually titrate when possible.

Inappropriate polypharmacy is a particular danger that needs to be addressed both during hospitalization and during PAC. Hal o the geriatric population is using more than ve medications. O these patients, 1 in 20 experiences an increase in morbidity and mortality. Not only does the patient su er the adverse e ects o the medication itsel , but they also experience interactions between medications and incur additional cost. There ore, prior to discharge, care ul review and relevant de-prescribing should be done to the bene t o patients. Step to reduce polypharmacy include: 1. Identi y potentially inappropriate medications (PIM) or the older adult using tools such as STOPP (Screening Tool o Older Persons’ Potentially Inappropriate Medications) with the reasons or stopping each medication. Medications or which there is little evidence or bene cial e ect should also 500

be discontinued. Down-titration is necessary prior to ull discontinuation or β-blockers, opiates, sedatives, gabapentin, clonidine, and selective serotonin reuptake inhibitors. I a medication cannot be stopped, the dose should be lowered when possible. 2. Medications should be eliminated when not consistent with the patient’s goals o care. Discontinuing some medications is appropriate i the patient is expected to pursue a palliative approach, or i estimated li e expectancy is likely too limited to obtain bene t rom a medication (such as a statin in the case o quickly progressive terminal cancer). 3. Medications that may pose higher risk or adverse e ects in older adults according to the “Beers” list should be reassessed, including sedative hypnotics, antidepressants, anticoagulants/ antiplatelet agents, hypoglycemic agents, opiates, and anticholinergic medications. There are o ten sa er alternatives or many o these drugs that should be chosen. One algorithm or reducing polypharmacy is illustrated below in Table 73-7A, through stepwise evaluation o the patient’s current medication risk and utility. Another use ul method, STRIP (Structured Tool to Reduce Inappropriate Prescribing) is a more concise, ve-step process with a yearly review: obtain a drug history, per orm an analysis o drugs, develop a treatment plan, review patient pre erences, and provide ollow-up and monitoring (Table 73-7B).

TABLE 73-7A Reducing Polypharmacy: Evaluation and Management* Evaluation 1. Ensure medication list is correct 2. Ascertain risk o adverse drug reaction - ≥8 Medications - Age >75 - High-risk medications 3. Prognosticate li e expectancy 4. De ines goals o care

5. Con irm indications or all drugs 6. Con irm need or preventative medications 7. Determine bene it vs harm using a tool (www.mdcalc. com) 8. Rank drugs rom high to low utility 9. Obtain patient consent or discontinuing the above drugs 10. Implement discontinuation or deprescribing plan (eg, tapering)

Corresponding Management

I 3 criterion met, reduce medication list to 5 or less medications

I li e expectancy 4 o 11 SLE criteria are met Multiorgan disease with + p-ANCA and ANA, low complement Skin changes, Raynaud’s phenomenon and visceral disease History, periarticular pain, e usions Skin biopsy: leukocytoclastic vasculitis with IgA and C3 deposition ARF with schistocytes on smear Low C1 esterase inhibitor level High-serum tryptase and urinary histamine; increased tissue mast cells Fever, con usion, thrombocytopenia, schistocytes (Continued)

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Abdominal migraine Temporal lobe seizures Radiculopathy Irritable bowel syndrome Renal Nephro/ureterolithiasis Papillary necrosis

C H P T E R 7 5 A c u t b d o m i n a

Unilateral, pain ul vesicular rash in dermatomal distribution, positive DFA o lesion or PCR o luid Adolescents, cyclic occurrence Adolescents, aura, abnormal EEG Mechanical pain in dermatomal distribution, positive MRI Manning or Rome III criteria

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Production o pain with rib compression only on a ected side Carnett’s sign Right upper quadrant (mainly) tenderness and positive Carnett sign

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Fever, hypotension, rash (CDC case de inition) Fever, rash, spasmodic pain, enterovirus (coxsackie/echo) Diarrhea, ever, positive stool culture, ileal in lammation Fever, atigue, diarrhea, right lower quadrant mass and ascites, positive biopsy Fever, HA, myalgias/arthralgias, low platelets, high LFTs, positive serology Fever, chill, diaphoresis, HA, myalgia, cough, multiorgan disease, red blood count smear

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Musculoskeletal “Slipping rib” (lower rib margin) syndrome Rectus sheath hematoma/neuroma Chronic abdominal wall pain syndrome Neurologic/Psychiatric Herpes zoster

Key Diagnostic Feature

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TABLE 75-1 Nonsurgical Disorders Causing Acute Abdominal Pain (continued)

Hematuria and positive CT Hematuria, obstructive uropathy, diabetes, sickle cell disease

ACTH, adrenal corticotropin hormone; ALA, aminolevulinic acid; ANA, antinuclear antibody; ARF, acute renal ailure; CDC, centers or disease control and prevention; CT, computed tomography; CT-PA, computed tomography-pulmonary angiography; CTA, computed tomography-angiography; DFA, direct luorescent assay; ECG, electrocardiogram; EEG, electroencephalogram; HA, headache; HTN, hypertension; IgA, immunoglobulin A; LFT, liver unction test; MRA, magnetic resonance angiography; MRI, magnetic resonance imaging; PCR, polymerase chain reaction; SLE, systemic lupus erythematosus; TCA, tricyclic antidepressants; TSH, thyroid stimulating hormone. Data rom Makrauer FL, Greenberger NJ. Acute abdominal pain: basic principles ¤t challenges. In: Greenberger NJ, Blumberg RS, Burako R, eds. Current Diagnosis &Treatment: Gastroenterology, Hepatology, &Endoscopy. New York, NY: McGraw-Hill; 2009:1-10.

colon and associated metabolic abnormalities. Embolism o the superior mesenteric artery may also cause acute abdominal pain because o the lack o preexisting arterial collaterals. Risk actors include cardiac arrhythmia, recent myocardial in arction, or proximal aortic disease. These patients typically do not have a history o intestinal angina. Cholesterol embolism may a ect branches and terminal arteries leading to segmental bowel involvement and abdominal pain without ocal ndings until necrosis o the entire bowel wall occurs. Mesenteric ischemia o venous origin is characterized by acute and chronic orms. The chronic orm causes abdominal pain and diarrhea, but does not usually progress to acute abdominal ndings. Risk actors include prior venous thromboembolism and primary hypercoagulable states, previous abdominal surgery, intra-abdominal cancer, in ammatory bowel disease, and portal hypertension. The acute orm is more likely to involve a major venous vessel such as the portal or superior mesenteric vein. The chronic orms may develop in small peripheral veins and progress proximally. Elderly vasculopathic patients are particularly prone to developing ischemic colitis—a clinically distinct entity rom mesenteric ischemia—in which small vessel insuf ciency results in sloughing o the metabolically active mucosal lining o the colon. This condition is o ten con used with in ammatory or in ectious colitis since it o ten presents with crampy pain and diarrhea (o ten positive or occult blood, and sometimes grossly bloody), and o ten with ever. Since this condition results rom small vessel insuf ciency, there is rarely any role or evaluation o mesenteric vessels.

THE PHYSICAL EXAMINATION

■ DOES THE PATIENT LOOK SICK? A patient who lies still, has his knees exed, and has a rigid abdomen most likely has peritoneal in ammation. Patients who are restless, unable to get com ortable, and pace may have renal colic or an aortic dissection. Patients with a perinephric abscess may bend over toward the involved side.

■ WHAT ARE THE VITAL SIGNS? Although lack o ever does not rule out an in ammatory process, especially in immunocompromised hosts, patients with renal ailure, or the elderly, its presence requires urther evaluation. Tachycardia may result rom pain rom any source, ever, and dehydration. Hypertension can arise rom any severe pain but may also predispose to vascular events. It is initially present in more than 70% o patients with acute aortic dissection. Hypotension in association with acute abdominal pain raises the possibility o aortic rupture or dissection, sepsis, gastrointestinal bleeding, dehydration, and pump ailure (acute myocardial in arction, pulmonary embolism). Patients may also develop nonocclusive mesenteric ischemia associated with a low-output state related to septic shock, myocardial in arction, and other causes o hypotension. Patients with chronic adrenal insuf ciency may experience nonspeci c abdominal pain and have relatively low blood pressures but otherwise appear well. Tachypnea may be associated with anxiety, severe pain, sepsis, acute pulmonary embolism, pneumothorax, and other respiratory causes. 517

■ ARE THERE ANY SIGNS OF SYSTEMIC ILLNESS?

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The abdominal examination may con rm the clinician’s pretest suspicion o an underlying disorder. However, most signs are use ul i present but not i absent. For example, elderly patients may have acute cholecystitis without any signs or symptoms in the right upper quadrant. The clinician’s gestalt has a reported LR+ 25 to 30 compared with a positive Murphy sign, LR 2.8 (0.8-8.6) and right upper quadrant tenderness, LR 1.6 (1.0-2.5). The presence o ecchymoses, signi ying subcutaneous blood rom intraperitoneal or retroperitoneal hemorrhage dissecting the skin overlying the anks (Turner sign), a periumbilical bruise (Cullen sign) or a green or jaundiced discoloration at the umbilicus (Ransoho sign o a ruptured bile duct) is help ul only i present. Prominent venous patterns may suggest portal hypertension or in erior vena caval syndrome but are also seen in normal elderly patients. Regarding ascites, the presence o a uid wave has a reported LR+ 6.0 (3.3-11) and shi ting dullness LR+ 2.7 (1.9-3.9). The absence o a uid wave or shi ting dullness does not rule out the presence o signi cant ascites in the patient with risk actors or symptoms o ankle swelling, weight gain, and abdominal distention. Palpating a liver edge below the right costal margin may increase the patient’s pain and correlates poorly with the actual liver span (LR+ 2.0). For patients with risk actors or splenomegaly, the reported LR+ or percussion o Traube space is 2.3 (1.8-2.9) and palpation 8.2 (5.8-12). The sensitivity o abdominal palpation in patients with a ruptured abdominal aneurysm, especially in obese patients or those who cannot relax their abdomen, is suf ciently low that emergent surgical consultation and imaging is required i the index o suspicion is suf ciently high. The LRs vary with the size o the aneurysm; or aneurysms >4 cm the reported LR+ is 16 (8.6-29).

Data rom Simel DL, Rennie D, eds. The Rational Clinical Examination. McGraw-Hill; 2008:27, 73, 147, 300, 613.

■ THE ABDOMINAL EXAMINATION Inspection The abdominal examination must be per ormed gently and careully to elicit localized and generalized peritoneal signs. The examiner should rst inspect the abdomen at the oot o the bed to detect visible peristalsis, asymmetry suggesting hernias or masses, and distention. Unless there are surgical scars or a prior term pregnancy, the umbilicus should be within 1 cm o the midpoint between the xiphoid and the pubis. Organomegaly, masses, or ascites may cause displacement o the umbilicus. Eversion or outward protrusion o an inverted umbilicus is not a reliable sign or chronic ascites. In generalized peritonitis, respiratory motion is not associated with movement o the abdominal wall. The clinician should also note any changes in skin color, the presence o ecchymoses, and the presence o scars. The presence o surgical scars increases the likelihood that abdominal adhesions may be causing acute pain. I the patient can attempt a modi ed sit-up 518

that contracts his rectus abdominal muscles, a ventral hernia may be more visible than palpable. Auscultation In general, auscultation or abnormal bowel sounds should be per ormed prior to per orming percussion or palpation o the abdomen. O note, the absence o bowel sounds may be normally present between episodes o normal bowel motility and, hence, is not speci c by itsel or advanced intestinal obstruction or secondary ileus rom in ammatory conditions such as pancreatitis, pyelonephritis, or peritonitis. In act, some experts believe that the examiner must listen or at least 1 to 2 minutes be ore concluding that the bowel sounds are in act absent. However, it is worthwhile to listen or the very high-pitched tinkles and rushes characteristic o small bowel obstruction. A succession splash suggests gastric outlet obstruction. An epigastric bruit with a diastolic component may suggest hemodynamically signi cant stenoses o branches o the aorta including the celiac axis and superior mesenteric artery as well as in disease o the aorta, or the renal arteries. Friction rubs may rarely be appreciated over an in amed gallbladder, splenic in arct, and in cases o hepatoma, cholangiocarcinoma, and metastatic carcinoma. A murmur due to compression o the splenic artery may be appreciated in patients with pancreatic carcinoma. Percussion Light percussion to estimate the liver span (with >15 cm consistent with liver enlargement) is the most reliable method to check or the presence o hepatomegaly. I the patient’s abdomen is distended, the examiner should look or signs o ascites ( uid wave, shi ting dullness) or perhaps per orm a bedside ultrasound. Likewise, the clinician should start with light percussion to determine whether splenomegaly is present. A ull bladder is de ned as at least 250 mL o urine. An enlarged bladder requires ultrasound con rmation due to the unreliability o the physical examination in detecting bladder distention. Palpation The examiner should always rst explain to the patient what the examination will entail and examine the most pain ul area last. The patient should be asked to distinguish between pressure and pain during examination o all quadrants. During the abdominal examination the patient’s hips and knees should be exed to relax the abdominal musculature. Involuntary guarding and rebound tenderness may be an indication o parietal peritoneal (layer o the abdominal wall) involvement, a rough or cold examining hand, or due to patient apprehension. The examiner should ask the patient to point to the area o pain. A patient with appendicitis may be able to precisely localize the pain using one nger, especially a ter coughing or per orming the Valsalva maneuver. A positive Murphy sign is elicited when the in amed gallbladder descends to the examiner’s thumb and causes pain suf cient to abruptly cease inspiration. The reported sensitivity o the Murphy sign is only 27% but increased with bedside ultrasound imaging the precise location o the gallbladder. Some experts do not recommend testing or rebound tenderness because the test is only use ul i positive and it causes unnecessary pain. I the pain is signi cantly out o proportion to the physical ndings, obstruction and ischemia should be suspected. To determine i abdominal pain is originating rom an intraabdominal source or the anterior abdominal wall, check or the Carnett sign. Have patient li t their head o the pillow resulting in increased tension in the anterior abdominal wall muscles thus protecting the structures within the abdomen rom the pressure o the examiner’s hand. I the pain is lessened by this maneuver, it indicates that the pain is arising rom an intraabdominal source. Conversely,

Koilonychia Onycholysis Beau lines Yellow nail

Terrys (white nails)

Asure lunula Hal -and-hal nails Muehrckes lines Mees lines

Splinter hemorrhage

Telangiectasis Skin lesions Gangrene, dependency rubor Pallor Jaundice Slate brown color Rash and ever Pyoderma gangrenosum Bruits Heart murmurs, gallops Pulmonary signs and symptoms Peripheral edema

Severe anemia (Hg < 7 g/dL) Liver disease, biliary tract disease, biliary obstruction Addison disease In ection In lammatory bowel disease Vascular disease Signi icant heart disease Pneumonia, pulmonary embolism, pneumothorax, empyema CHF, ascites, deep venous thrombosis

C H A P T E R 7 5 A c u t e A b d o m i n a l P a

Findings Clubbing

Systemic Disease That May be Associated with Abdominal Pain In lammatory bowel disease, pulmonary malignancy, cirrhosis, congenital heart disease, endocarditis (bacterial endocarditis), artrioventricular mal ormations, istulas Iron de iciency anemia, systemic lupus erythematosus (SLE) Hyperthyroidism, amyloidosis, connective tissue disorders Any severe systemic illness that disrupts nail growth Rheumatoid arthritis (RA), nephritic syndrome, tuberculosis, immunode iciency Hepatic ailure, cirrhosis, diabetes, congestive heart ailure (CHF), hyperthyroidism, malnutrition Wilson disease, silver poisoning Chronic renal ailure, cirrhosis Hypoalbuminemia Arsenic poisoning, Hodgkins disease, CHF, leprosy, malaria, carbon monoxide poisoning, other systemic insults Subacute bacterial endocarditis, SLE, RA, antiphospholipid syndrome, peptic ulcer disease, malignancies RA, SLE, dermatomyositis, scleroderma Vasculitis, septic emboli Peripheral vascular disease

A 57-year-old man developed acute right upper quadrant abdominal pain that radiated to his back. Similar to prior episodes, the pain was severe, abrupt onset, colicky in nature, lasting 45 to 60 minutes ollowed by an aching right upper quadrant discomort lasting several hours. His laboratory tests, including CBC, comprehensive metabolic pro le, serum amylase and lipase, urinalysis without the presence o bilirubin, and esophagogastroduodenoscopy, were all normal. Three ultrasound examinations obtained during three separate Emergency Department visits visualized the gallbladder but did not detect gallstones. On physical examination the patient had normal vital signs and his blood pressure was equal in both arms. His heart and lung examination was normal. Examination o the abdomen revealed thump tenderness in the right upper quadrant but not the le t upper quadrant, thump tenderness over the right lower anterior chest but not the le t lower anterior chest, and a palpable liver that was tender to deep palpation. The gallbladder which is usually identi ed by the junction o the right lateral rectus muscle and the costal margin was not palpable. Consistent with gallbladder disease but in the absence o stones, the clinical picture o this case is termed acalculous cholecystopathy. Delayed gastric emptying characterized by postprandial bloating and distention is less likely due to long intervals between acute attacks. A HIDA scan with injection o cholecystokinin would be the next test to per orm. It should reproduce the patient’s pain during his attacks and show a reduced gallbladder ejection raction to 50 y, ailure to improve with conservative therapy, pain > 1 mo, previous history o cancer, insidious onset, systemically unwell Pain rom bony metastatic disease becomes constant, dull, unrelieved by rest, and worse at night unlike mechanical low back pain Risk factors • Recent epidural anesthesia, spine surgery, procedure such as intrathecal devices • Anticoagulant use or coagulation disorder, thrombocytopenia Symptoms • Sudden, severe back or neck pain around the involved vertebrae with radiating pain • Within hours to days, ascending numbness, radicular paresthesia, and progressive paraparesis may develop Treatment • Early decompressive laminectomy with hematoma evacuation is essential Risk factors • IVdrug use or longer-term catheter placement, recent bacterial in ection, immunosuppression rom steroids, HIV, or organ transplantation Symptoms • Fever, neurologic symptoms Risk factors • History o herniated disks Symptoms • Loss o bowel or bladder unction, saddle anesthesia, widespread, or progressive motor weakness Risk factors • Age > 70 y, signi icant trauma, prolonged use o corticosteroids, altered sensation rom trunk down, diagnosis o racture Symptoms • When symptomatic, the pain with a compression racture may be sharp or dull, localized and may arise acutely or insidiously. Sitting or moving may aggravate the pain while laying supine is usually the most com ortable position Risk factors • Family history o AS, personal history o psoriasis, uveitis, in lammatory bowel disease, or recent in ection Symptoms • Gradual onset be ore the age o 40 y • Worse with rest and improved with exercise • Morning sti ness ≥ 0.5–1.0 h • Peripheral joint arthritis

PRACTICE POINT

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Most spine tumors compress rather than invade. In patients with a history o cancer and progressive spinal cord symptoms, especially involving bowel and bladder, assume that cord compression is the cause o their back pain until proven otherwise. Weakness usually a ects the legs rst, so be sure to check motor unction o the lower extremities. Also check position and vibration sense, which are very sensitive or compression.

Clinical Findings Thoracic aortic dissection and myocardial in arction See Chapter 128: Acute Coronary Syndromes See Chapter 255: Diseases o the Aorta Cancer, in lammatory back pain associated with ankylosing spondylitis (AS) Bony metastatic disease See Chapter 176: Hematologic Urgencies and Emergencies Spinal hematoma See Chapter 64: Common Complications in Neurosurgery

Osteomyelitis o the vertebral body or epidural abscess See Chapter 193: Osteomyelitis and Septic Arthritis Cauda equina syndrome

Vertebral compression racture Vertebral osteomyelitis (spondylodiskitis)

Axial spondyloarthritis

A straight leg-raising (SLR) test is per ormed with the patient supine, and the examiner’s hand holding the leg straight and cupping the heel. This maneuver stretches the L5 and S1 nerve roots and the sciatic nerve. Passive dorsi lexion o the oot urther increases the stretch. Reproducing the patient’s back or extremity pain with leg elevation to less than 60° is considered a positive test. Tight hamstring muscles may limit the degree o elevation without pain but would not be expected to reproduce the patient’s presenting pain. A positive crossed SLR test reproduces the patient’s symptoms in the opposite leg rom the

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TABLE 76-4 Neurologic Examination

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Lateral cal , dorsal oot, posterolateral thigh, buttocks

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Knee, medial cal Anterolateral thigh

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Pain Distribution Anterior thigh Anterior thigh, knee

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Motor Psoas (hip lexion) Psoas (hip lexion) Quadriceps (knee extension) Thigh adduction Quadriceps (knee extension)? Thigh adduction Tibialis anterior ( oot dorsi lexion) Peroneii ( oot eversion)? Tibialis anterior ( oot dorsi lexion) Gluteus medius (hip abduction) Toe dorsi lexors Gastrocnemius/soleus ( oot plantar lexion)? Abductor hallucis (toe lexors)? Gluteus maximus (hip extension)

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Sensory Upper anterior thigh Lower anterior thigh Anterior knee

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Bottom oot, posterior cal , posterior thigh, buttocks

*Reverse straight leg–raising sign present—see “Examination o the Back.” ? These muscles receive the majority o innervation rom this root. § Straight leg–raising sign present—see “Examination o the Back.” Reproduced, with permission, rom Fauci AS, Braunwald E, Kasper DL, et al. Harrison’s Principles of Internal Medicine, 17th ed. New York, NY: McGraw-Hill; 2008, Table 16-2.

lexed limb. This maneuver is less sensitive but more speci ic or lumbosacral radiculopathy. The examiner should also per orm a hip examination because hip pain can be con used with low back pain and any patient with bacteremia can seed the hip as well as the spine. The purpose o the neurologic assessment is to identi y de cits that would require emergent neurosurgical consultation and to document a baseline examination in the event that the patient goes to surgery (Table 76-4). Ask the patient to walk. I a patient is unable to walk due to weakness, the examiner should look or ocal weakness that may suggest a cord compression or spinal hematoma. In patients with spinal stenosis, walking in a orward-hunched position may relieve the pain with ambulation (anthropoid posture). These patients may have a positive Romberg maneuver, a wide-based gait, and claudication on orced lumbar extension, but are unlikely to have motor signs or weakness (Table 76-5). Asymmetric ref exes may assist in localization o the de ect: • Hyporef exia o the patellar ref ex: disk herniation at L4; Achilles

ref ex: disk herniation at S1 • Hyperref exia below the lesion: spinal cord compression, spinal hematoma, spinal stenosis. Note whether clonus is present • Absent perirectal tone and perineal sensation: cauda equina syndrome

PRACTICE POINT

•

The examiner should document the timing and nature o any bowel, bladder, motor, and sexual dys unction once a diagnosis that may be associated with neurologic compromise is suspected. Be sure to record any de cits prior to surgical intervention.

USE OF IMAGING TO EVALUATE BACK PAIN IN HOSPITALIZED PATIENTS Back pain is a common, o ten chronic, problem that may not require evaluation during hospitalization. Early magnetic resonance imaging (MRI) in outpatients without serious neurologic or systemic signs or symptoms does not alter treatment or overall quality o low back pain a ter 8 and 24 months. The presence o degenerative lumbar disk changes o herniation, degeneration, or an annular ssure do not correlate with symptoms, and are also seen in 14% to 50% o healthy volunteers. However, hospitalized patients are a di erent population. For patients with chronic pain in particular, it is important to determine whether the patient has had prior appropriate imaging, i the patient has had a procedure during or prior to hospitalization that might result in complications a ecting the spine, and whether the patient’s symptoms have changed or simply noted during review o symptoms. The presence o additional signs, symptoms, and underlying chronic disease conditions determines the proper di erential diagnosis and direct selection o imaging. New back pain demands care ul consideration o causes or which prompt imaging will avoid catastrophic e ects upon patient outcome. Aortic dissection is characterized by back pain and may be accompanied by chest pain or abdominal pain. Physical examination may reveal hypertension, di erential blood pressures, pulsus paradoxus, and possibly a pulsatile aorta in addition to evidence o organ compromise, depending on the location and extent o dissection or it may be unrevealing. Recent angiography or other vascular intervention may also increase concern. The diagnosis o dissection and determination o extent must be undertaken emergently. In this case, the rapidity with which the examination can be per ormed outweighs the imaging modality selected. CT and MRI are both widely used or evaluation o the entire aorta. Dissection may also be diagnosed on angiography and ultrasonography although the extent o dissection 529

TABLE 76-5 Targeted History and Physical Examination of the Spine

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Symptoms including reported neurologic deficits Onset including precipitating factors: Examples: cord contusion ollowing hyperextension o the spine due to severe trauma with underlying pathology causing stenosis or instability or rarely, spontaneous epidural hematoma ollowing valsalva maneuvers with coughing and sneezing, cocaine use, back manipulation, and even exercise. Pain (mild, moderate, severe; bilateral vs unilateral; radiating) Bladder/bowel Sensory Motor Vital signs Lability o BP (very labile with cord lesions, especially during pain) Speci ically note presence o hypotension, ever in last 24 h Cardiac examination Murmurs (especially i ever present or known bacteremia) Pulmonary New signs suggestive o pneumonia (especially i ever or known bacteremia) Abdomen Bowel sounds Check or tenderness, guarding, presence o pulsatile mass Percussion o bladder i urinary retention suspected Vascular BP in both arms Pulses, including examination o extremities or cyanosis Bruits Bowel/bladder Presence o Foley catheter or diapers Evidence o urinary retention Spine Alignment Tenderness Spasm Deep tendon reflexes (biceps, triceps, brachioradialis, knee, ankle, Babinski) I brisk, check clonus, spreading I spine cord injury suspected, check abdominals, suprapubic, cremasteric, anal re lexes (place a gloved inger in the patient’s anal canal to check the “anal wink” or contraction o external anal sphincter in response to noxious stimuli; place a inger on the perineum right behind the scrotum, pull on penis or bladder catheter to check the bulbocavernosus re lex or contraction o the cavernosus muscle) Straight leg raise to reproduce patient’s pain: L5, S1 Reverse straight leg raise: L3 or L4 Hip FABER (put ankle on opposite knee; rotate knee toward examination table) positive or mechanical LBP or hip pathology but not or disk disease Patrick sign (internal and external rotation at the hip with hip and knee in lexion) Heel percussion sign (tapping heel when extremity extended) Motor De icits (slow movements; ast but weak movements; arms compared to legs) Atrophy Fasciculations Tone (rigidity, spasticity) Gait Sensory Pin Light touch Temperature Cranial nerves (i leptomeningeal metastases suspected)

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PRACTICE POINT

•

Consult with the radiologist at your institution to determine the best emergent imaging study and whether contrast is required to avoid unnecessary delays and to avoid imaging studies that do not rule out the condition you suspect.

In an elderly woman with known osteoporosis, back pain may arise rom an acute compression racture o a vertebra and be conrmed by chest radiographs or radiography o a single region o the spine. Osteoporosis is also associated with chronic disease and treatments, such as steroids making this an even more common possibility among hospitalized patients. Some conditions cause bone de ormities that also increase potential or mild trauma to become devastating during a hospitalization. It is important to remember that endoscopic examinations and intubation can stress abnormal spines setting up catastrophic complications. In a patient with rheumatoid arthritis, new-onset neck pain may indicate a C1–C2 subluxation. In a patient with AS, new-onset neck pain may indicate an unstable racture o the used cervical spine. In either case neck immobilization should precede cervical spine imaging. MANAGEMENT

CASE 76-3 NONEMERGENT HOSPITALIST ADMISSION FOR BACK PAIN A35-year-old construction worker was evaluated in the emergency department with severe low back pain that had been ongoing or 4 days and has culminated in limiting his ability to walk. He had never had back pain be ore and the pain was described as dull and constant but markedly worse on ambulation. The pain did not arouse the patient once he was able to all asleep. Acetaminophen and ibupro en taken intermittently had not relieved the pain. He denied any pain in his lower extremities, numbness, tingling, or any bowel or bladder symptoms, sexual dys unction, chest pain, shortness o breath, nausea, vomiting, or abdominal pain. There had been no ever or weight loss. His review o systems was otherwise unremarkable. He drank six to ten beers on a daily basis

C H A P T E R 7 6 A c u t e B a c k P a i

and had been smoking a pack a day or 7 years. He occasionally used intranasal cocaine on a recreational basis. He denied using intravenous illicit drugs and reported no HIV risk actors. He has recently started working in his current job, which involves heavy li ting. He reported that his mother has hypertension and his ather has both hypertension and a prior history o a myocardial in arction. He also reported a younger brother who has psoriasis. On exam the patient was a ebrile. His pulse was 88 beats per minute, and his blood pressure was 140/80 mm Hg. Respirations and pulse oximetry were normal while breathing ambient air. The examination was signi cant or a negative straight leg test. He had ull range o motion o his cervical spine and tenderness to palpation o the paraspinal muscles at the lumbar and sacral spine. His upper extremity strength was 5/5 in all muscle groups but it was dif cult to assess his lower extremity strength due to pain with any motion. His labs were signi cant or a white blood cell count o 9000/mm 3, a normal erythrocyte sedimentation rate, and normal PA and lateral lms o the thoracic and lumbar spine. His pain was mildly improved with intravenous hydromorphone at 2 mg every 4 hours, but he was still not able to walk. The hospitalist on duty was contacted to assess this patient or a possible admission. What emergent causes o back pain will need to be ruled out prior to discharge? What are the more common nonemergent causes o this type o back pain? What are the next steps in this patient’s management? How can this patient be sa ely transitioned to the outpatient setting? The above case represents a patient who did not appear to have “red ags” that would suggest an emergent cause that would warrant any urther testing in an inpatient hospital setting. The history and physical examination in the ED were consistent with acute low back pain that did not portend serious underlying pathology. His presentation was not consistent with a cardiopulmonary pathology. He had no worrisome lab values consistent with an in ection or an in ammatory state. His neurologic review o systems and exam did not suggest an acute lumbar disk protrusion leading to the cauda equina syndrome. He was not presenting a history or exam consistent with in ammatory back pain and a spondyloarthritis. I the patient continued to have dif culty ambulating, an admission or IV ketorolac ollowed by a transition to oral ibuproen (with or without a proton pump inhibitor given his alcohol consumption) might be warranted. Based on the patient’s wishes and ability to ambulate within the next 12 hours, a social work consultation as well as an inpatient physical therapy consultation was recommended. The patient might be prescribed ibupro en at 1800 to 2400 mg in three divided doses or 5 days, with consideration o a proton pump inhibitor upon discharge. He should see his primary care physician within 2 weeks o his hospitalization. The patient might also be prescribed cyclobenzaprine at a dose o 10 mg orally at night or the rst 2 weeks. It is vital that personto-person communication between the inpatient team and the primary care physician be established in all cases where compliance is in question or when other speci c case peculiarities have arisen during the hospital stay.

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may be outside the imaging that is being per ormed or other purposes. The care ul evaluation o images by the radiologist makes a critical di erence in patient care, particularly when dissection is the cause o back pain or which a spine MRI has been ordered. Any condition leading to impending cord compression is a reason or emergent MRI examination. There is one exception—trauma. In the setting o trauma, since the most help ul identi cations are o bone ragments, CT would be chosen over MRI or initial workup because calcium voids are a limitation o MRI. Regarding cancer and in ection, it is the presence and degree o cord compression that is the real emergency issue, as opposed to whether the etiology is due to tumor or in ection. Radiography, radionuclide bone scans, and CT scans are help ul or identi ying musculoskeletal metastases rom a wide variety o tumors but MRI allows identi cation o nerve roots and tumor extension into the thecal sac. I cancer is suspected, MRI imaging o the entire spine is indicated. Like cancer, epidural abscess usually requires rapid identi cation and treatment to prevent permanent neurologic de cit. CT may miss a signi cant epidural collection that could suddenly cause neurologic compromise; thus, MR is pre erred. With concerns about the risks o IV contrast enhancement, higher eld strengths may allow more alternatives to IVcontrast enhancement o MR sequences.

Initial management requires a decision about consultation. For interhospital trans ers and patients admitted through the emergency department, it is very important to consider a wide range o diagnostic possibilities, in addition to the provisional diagnosis. When a patient is trans erred rom an outside hospital or intractable back pain, conservative management generally has ailed, and emergent consultation with specialists, including neurosurgery, should be considered. The outside lms should be reviewed with 531

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PRACTICE POINT

Caragee E. Persistent low back pain. Clinical practice. N Engl J Med. 2005;352:1891-1898.

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a radiologist to guide the need or additional imaging. Emergent imaging may be required i there are red f ags suggestive o in ection or other serious pathology, or technical limitations o the outside lms. See Chapter 99 (Pain).

Indications or emergent neurosurgical consultation include decompression o the spine in the setting o epidural abscess, tumor, or hematoma; urgent need or a tissue diagnosis; spinal instability, with displaced bone or ligaments; and metastatic disease that has recurred despite radiation therapy.

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Clinicians need to assimilate the history and physical examination within the context o a new patient—one whose personality, pain tolerance, and unique qualities may not be apparent during a single encounter. Clinically excluding li e-threatening and neurologically serious possibilities may require taking advantage o all the resources in the hospital including care ul review o the chart, communication with caregivers who know the patient best, raming appropriate questions about risk actors and antecedent events, and emergent consultation and imaging. Although in general, hospitalists should avoid the temptation to pursue unnecessary and expensive diagnostic imaging when chronic conditions do not require inpatient workups such as spinal stenosis, it is also critical to advocate or appropriate and emergent imaging studies in selected patients based on rational choices. The responsible attending should always ask the question: What are the kinds o things that cannot be missed such as acute cord compression that may require emergent surgery and radiation therapy? In these instances, MRI may be the only imaging modality that will give you the in ormation that you need. Although there is a vast literature about back pain

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SUGGESTED READINGS

Chou R, Hoyt Hu man L. Medications or acute and chronic low back pain: a review o the evidence or an American Pain Society/ American College o Physicians Clinical Practice Guideline. Ann Intern Med. 2007;147:505-514. Gilbert FJ, Grant AM, Gillan MG, et al. Low back pain: inf uence o early MR imaging or CT on treatment and outcome-multicenter randomized trial. Radiology. 2004;231:343-351. Henschke M, Maher CG, Re shauge KM. A systematic review identies ve “red f ags” to screen or vertebral racture in patients with low back pain. J Clin Epidemiol. 2008;61(2):110-118. Henschke N, Maher C, Re shauge K. Prevalence and screening or serious spinal pathology in patients presenting to primary care setting with acute low back pain. Arthritis Rheum. 2009;60:3072-3080. Henschke N, Maher CG, Re shauge KM. Screening or malignancy in low back pain patients: a systematic review. Eur Spine J. 2007;16:1673-1679. Katz JN, Harris MB. Lumbar spinal stenosis. N Engl J Med. 2008;358:818-825. Klinberg E, Mazanec D, Orr D, et al. Masquerade: medical causes o back pain. Cleve Clinic J Med. 2007;74:905-913. Lavy C, James A, Wilson-MacDonald J, et al. Cauda equina syndrome. BMJ. 2009;338:881-884. Wilco C, Hans C, Wilbert B, et al. Surgery versus prolonged conservative treatment or sciatica. N Engl J Med. 2007;356:2245-2256.

77

CHAP TER

Evaluation of Anemia

INTRODUCTION According to the World Health Organization (WHO), anemia is de ned as a hemoglobin concentration o less than 13 g/dL in men and less than 12 g/dL in women. Anemia is common among hospitalized patients. In this chapter, we ocus on the evaluation o acute presentations o anemia in hospitalized patients, outlining a practical approach or assessment with emphasis on di erentiating common disorders rom rare potentially li e-threatening conditions. We also provide case vignettes to illustrate typical presentations o anemia encountered in this setting. CLASSIFICATION OF ANEMIA IN THE ACUTE CARE SETTING

Deborah M. Siegal, MD, MSc, FRCPC Madeleine Verhovsek, MD, FRCPC

Anemia can be classi ed broadly by the underlying pathophysiological mechanism o blood loss, increased RBC destruction, or reduced RBC production (Table 77-1).

■ BLOOD LOSS Blood loss leading to anemia may be acute or chronic. With acute bleeding, the initial hemoglobin concentration and hematocrit do not accurately represent the actual volume o blood loss. Reductions in hemoglobin concentration may not become apparent or several hours a ter the onset o bleeding. Clinical presentation is o ten characterized by signs o hemodynamic compromise, including hypotension, tachycardia, and hypoper usion. Acute blood loss may be overt (eg, hematochezia, melena, hematemesis, epistaxis) or occult (eg, retroperitoneal hemorrhage). A high index o suspicion or occult acute bleeding should be maintained in patients receiving antiplatelet or anticoagulant therapies, or those with known bleeding diatheses who present with acute anemia and no obvious source o bleeding. In the perioperative setting, worsening anemia should be investigated or occult bleeding at the operative site (eg, retroperitoneal, intra-abdominal, periprosthetic). Chronic blood loss causes anemia through depletion o iron, which is required or erythropoiesis. Patients with chronic blood loss may present to hospital with progressive symptoms o anemia such as chest discom ort, palpitation, dyspnea, syncope, or severe atigue requiring urgent assessment and management. Unexplained iron de ciency anemia requires endoscopic evaluation to exclude occult blood loss rom gastrointestinal lesions including malignancy. For patients with prolonged hospital admissions, iatrogenic blood loss rom requent diagnostic testing may contribute signi cantly to blood loss leading to anemia.

PRACTICE POINT

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With acute blood loss, the initial hemoglobin concentration and hematocrit may not ref ect the volume o blood loss. Reductions in hemoglobin concentration may not become apparent or several hours a ter the onset o bleeding.

■ REDUCED RBC PRODUCTION Erythropoietin is a hormone produced predominantly by the kidneys, which stimulates RBC production in the bone marrow in the presence o adequate nutrients such as olate, vitamin B12, and iron. Impaired RBC production can result rom an abnormality in erythropoietin production (eg, chronic kidney disease) or a disorder 533

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TABLE 77-1 Classification of Anemia Based on Pathophysiology

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Decreased RBC Production Substrate de iciency (iron, olate, or vitamin B12 de iciency) Anemia o chronic in lammation Myelodysplastic syndrome Bone marrow in iltration (eg, lymphoma, myeloma, leukemia, myelo ibrosis, metastatic malignancy) Bone marrow ailure syndrome (congenital or acquired) Chronic kidney disease Liver disease

Increased RBC Destruction (Hemolysis) Immune mediated •  Autoimmune •  Alloimmune •  Drug induced

Blood Loss Acute or chronic blood loss

Nonimmune mediated •    Microangiopathic (TTP/HUS, DIC, HELLP, SRC, malignant hypertension) •    Mechanical (eg, cardiac valve hemolysis) •    Thermal (eg, burn injury) •    PNH RBC membrane de ect •    Hereditary spherocytosis •    Hereditary elliptocytosis Hemoglobin de ect •    Thalassemia •    Sickle cell anemia RBC enzyme de ect •    G6PD de iciency •    PKde iciency

DIC, disseminated intravascular coagulopathy; G6PD, glucose-6-phosphate dehydrogenase; HELLP, hemolysis elevated liver enzymes low platelets; HUS, hemolytic uremic syndrome; PK, pyruvate kinase; PNH, paroxysmal nocturnal hemoglobinuria; RBC, red blood cell; SRC, scleroderma renal crisis.

a ecting the ability o bone marrow precursors to respond to erythropoietin (eg, nutritional de ciency, bone marrow replacement, abnormal RBC maturation). Iron de ciency is the most common cause o hypoproli erative anemia, especially among emales o child-bearing age. Iron de ciency in males or postmenopausal emales should prompt consideration o occult gastrointestinal blood loss or malabsorption. Other disorders commonly associated with reduced RBC production include chronic inf ammation, renal disease, liver disease, and hypothyroidism. Folate and vitamin B12 de ciency cause impaired DNA synthesis, and subsequent reduced erythropoiesis. Chemotherapeutic agents, immunosuppressive drugs, and ethanol commonly suppress RBC production. In ectious agents such as parvovirus B19, human immunode ciency virus, may also be associated with hypoproli erative anemia. RBC production can result rom marrow in ltration by metastatic malignancy, hematologic malignancy (eg, lymphoma, myeloma, leukemia), or myelo brosis. Myelodysplastic syndrome is a primary clonal bone marrow disorder resulting in abnormal maturation o bone marrow precursors leading to peripheral cytopenias, including anemia. Pure red cell aplasia and aplastic anemia are less common bone marrow ailure syndromes. Stable hospitalized patients requently develop multi actorial anemia due to suppression o RBC production rom in ection, inf ammation, malignancy, and/or renal impairment that can accompany acute medical illness. 534

■ INCREASED RBC DESTRUCTION The normal RBC li e span is approximately 120 days. Hemolysis is the premature breakdown o RBCs. The severity o anemia resulting rom hemolysis depends on the rate o hemolysis and the ability o the bone marrow to compensate by increasing RBC production. Hemolysis may be congenital or acquired. Although some congenital hemolytic conditions present earlier in li e (eg, thalassemia major, sickle cell disease), others associated with mild-to-moderate hemolysis may be clinically silent until later in li e (eg, hereditary spherocytosis [HS], glucose-6-phosphate dehydrogenase [G6PD] de ciency, β-thalassemia intermedia, hemoglobin H disease). Causes o hemolysis can be classi ed according to etiologies intrinsic or extrinsic to the RBC (see Figure 173-1). Intrinsic actors include abnormalities o the RBC membrane (eg, hereditary spherocytosis, hereditary ellipticytosis), hemoglobin (eg, thalassemias, sickle cell disease), or RBC enzymes (eg, G6PD de ciency, pyruvate kinase de ciency). Extrinsic causes include immune-mediated (alloor autoantibodies) or nonimmune mediated (microvascular or macrovascular mechanical RBC damage). O ten extrinsic causes will present acutely in patients with no prior hemolytic issues. Patients with chronic hemolytic anemia may present to hospital with acute exacerbations o their underlying condition mani ested generally as jaundice, atigue, and exertional dyspnea. In patients who have received RBC trans usion in the preceding 4 weeks, eatures o acute hemolysis may be due to a delayed hemolytic trans usion reaction (DHTR). DHTR occurs when patients develop an alloantibody to antigens on the trans used blood, which can be identi ed on antibody investigations by the trans usion medicine laboratory. APPROACH TO DIAGNOSISAND INITIAL MANAGEMENT A systematic approach to diagnosis starts with a detailed history including medication review, physical examination, and laboratory testing. In the acute setting, initial management should ocus on assessment o hemodynamic stability in a monitored setting. For acute bleeding, resuscitative measures (eg, intravenous f uids, trans usion) and local hemostatic measures (eg, compression, packing, splinting) should be applied as necessary with early re erral or procedural/surgical intervention. Laboratory tests evaluating possible etiologies o anemia including complete blood count (CBC), reticulocyte count, peripheral blood lm, erritin, trans errin saturation, vitamin B12, haptoglobin, lactate dehydrogenase (LDH), and direct antiglobulin test (DAT or Coombs test) should be considered as part o initial investigations prior to administration o RBC trans usion, which can inter ere with the interpretation o these tests and the ability to correctly identi y the underlying cause.

PRACTICE POINT

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Laboratory tests evaluating possible etiologies o anemia include complete blood count (CBC), reticulocyte count, peripheral blood lm, erritin, trans errin saturation, vitamin B12, haptoglobin, lactate dehydrogenase (LDH), and direct antiglobulin test (DAT or Coombs test). These tests should be considered as part o initial investigations prior to administration o RBC trans usion, which can inter ere with the interpretation o these tests and the ability to correctly identi y the underlying cause.

RBC trans usion is a scarce resource with associated health risks and should be reserved or patients with severe symptomatic

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In patients with acute bleeding, RBC trans usion should be provided to maintain hemoglobin above 7 g/dL. The threshold or RBC trans usion in stable critically ill patients is 7 g/dL. The trans usion threshold or patients with acute coronary syndrome is uncertain, but RBC trans usion should be considered i the hemoglobin is low and there are signs o poor tissue oxygen delivery.

■ HISTORY A care ul medical history can reveal important in ormation regarding the time course and possible underlying etiologies. Fatigue is a nonspeci c symptom but the onset and progression can be help ul to establish a timeline. The presence and progression o additional symptoms such as dyspnea, chest discom ort, palpitation, dizziness, syncope, jaundice, and dark urine can also be help ul. A history o overt bleeding (eg, hematochezia, melena, hematemesis, vaginal bleeding) should be sought. Fever, chills, drenching night sweats, unexplained weight loss, and mass lesions are concerning or underlying malignancy or in ection. Excessive bruising and petechiae are suggestive o thrombocytopenia or coagulopathy that can accompany bone marrow ailure/in ltration, disseminated intravascular coagulation (DIC), microangiopathic hemolytic anemia (MAHA), malignancy, or in ection. Alcohol intake, illicit drug use, and history o sexually transmitted in ections should also be evaluated. There may be a amily history o anemia or other hematologic disorders. Details regarding chronic medical conditions should be elicited with particular emphasis on hematologic/red blood cell disorders,

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cachexia, rash, koilonychia (spoon nails), angular cheilitis Vital signs: tachycardia, hypotension, tachypnea, hypoxemia, ever Cardiovascular system: jugular venous distension, systolic (f ow) cardiac murmur Head and neck: lymphadenopathy, thyroid abnormalities Abdomen: masses, hepatomegaly, splenomegaly, digital rectal exam or blood or melena Central nervous system: level o consciousness, ocal neurologic de cits

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A comprehensive physical examination should evaluate or the ollowing:

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renal disease, liver disease, chronic inf ammatory conditions, disorders o malabsorption, and malignancy. Pharmacological agents can cause bone marrow suppression and hemolysis and a complete review o all prescription, over-the-counter, and naturopathic medications is essential (Table 77-2).

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anemia. In unstable bleeding patients, RBC trans usion should be provided to maintain hemoglobin over 7 g/dL, to replace the volume o blood lost and maintain oxygen carrying capacity. In stable critically ill patients, RBC trans usion should be provided when hemoglobin is less than 7 g/dL. Trans usion thresholds or patients with acute coronary syndromes are uncertain and RBC trans usion should be considered or such patients with low hemoglobin and signs o inadequate tissue oxygen delivery. For patients with ongoing, brisk hemolysis, clinicians must take into account the patient’s symptoms o anemia, rate o hemolysis, and reticulocyte response when determining whether to include RBC trans usion in initial management. Frequent serial monitoring o hemoglobin concentration is o ten required be ore deciding on necessity and volume o trans usion. For patients with sickle cell disease, we recommend against trans usion or uncomplicated sickle pain episodes, i hemoglobin concentration is near the patient’s baseline, and there is appropriate reticulocytosis.

■ LABORATORY TESTING Evaluation o the complete blood count (CBC), reticulocyte count, RBC mean corpuscular volume (MCV), and review o the peripheral blood lm is essential or identi ying potential etiologies (Table 77-3). Table 77-4 shows suggested laboratory tests or investigation o anemia with low (microcytic), normal (normocytic), or high (macrocytic) MCVbased on the suspected underlying cause. In the setting o brisk hemolysis or blood loss, the peripheral blood lm may show evidence o increased RBC production with the presence o less mature RBC orms including polychromasia (indicative o reticulocytosis) and nucleated RBCs (immature orms). Other ndings suggestive o hemolytic conditions include spherocytes (autoimmune hemolytic anemia, hereditary spherocytosis), RBC agglutination (cold autoimmune hemolytic anemia), RBC ragments (DIC, microangiopathic hemolytic anemia, mechanical ragmentation), bite/blister cells (oxidative damage, G6PD), and copious target cells (thalassemias) (see Table 173-2). The reticulocyte count is a marker o RBC production reported as an absolute count or as a percentage. The normal reticulocyte count is approximately 50,000/µL to 100,000/µL in the absence o anemia, although re erence ranges vary between automated methods or measurement. Local re erence ranges should be used. When expressed as a percentage, the reticulocyte count is corrected or hematocrit, age, and gender. In the setting o anemia, an absolute reticulocyte count 100 L) Megalobalstic anemia Vitamin B12 de iciency Folate de iciency Myelodysplastic syndrome Liver disease Alcohol Hypothyroidism Reticulocytosis Drugs (eg, hydroxyurea)

count ≥100,000/µL or corrected reticulocyte count greater than 2% suggests increased production o RBCs as a response to hemolysis or bleeding. Coexisting thrombocytopenia may contribute to active bleeding or may be a sign o a process a ecting both cell lines (eg, TTP, DIC, bone marrow ailure, liver disease). Increased white blood cell count

(WBC) should prompt review o the WBC di erential, and consideration o relevant contributing processes (eg, in ection, malignancy), while low WBC may be indicative o bone marrow underproduction or autoimmune conditions.

■ SUMMARY Anemia is a common nding among hospitalized patients and is o ten multi actorial in nature. In ection, inf ammation, malignancy, renal ailure, and hepatic dys unction contribute signi cantly to anemia in this setting. Preliminary investigations should be directed at excluding li e-threatening and common causes o anemia. Subsequent specialized investigations should be directed by the results o preliminary testing or reserved or patients with persistent unexplained anemia ollowing resolution o the acute illness. Key questions to help guide investigations and emergent consultation: • Is the anemia acute or chronic? • Is there an identi able reversible cause (eg, iron de ciency, • • •

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vitamin B12 de ciency)? Is there overt bleeding? Has the patient had recent surgery? Are there abnormalities on the CBC or peripheral blood lm suggesting a primary hematologic disorder (eg, schistocytes, spherocytes, target cells, thrombocytopenia, neutropenia, blasts)? Is the patient receiving medications known to cause anemia? Does the patient have underlying metabolic abnormalities (eg, renal or liver ailure), in ection, inf ammation, or malignancy?

CASE VIGNETTES

CASE 77-1: ANEMIA IN THE INTENSIVE CARE UNIT A 48-year-old previously healthy male was admitted to the intensive care unit 2 weeks ago with pneumonia, sepsis, and acute kidney injury requiring renal replacement therapy. He is being treated with antibiotics and remains on a mechanical ventilator

TABLE 77-4 Suggested Laboratory Tests Based on Initial RBC Size Microcytic Anemia (MCV < 80 L) Initial tests • CBC with reticulocyte count • Peripheral blood ilm • Ferritin Supplementary tests • Iron studies (serum iron, iron saturation, iron binding capacity) • In lammatory markers (ESR, CRP) • Hemoglobinopathy screen (hemoglobin electrophoresis) • Lead level • Copper level

Normocytic Anemia (MCV 80-100 L) Initial tests • CBC with reticulocyte count • Peripheral blood ilm • Ferritin • Hemolytic testing (eg, haptoglobin, ree hemoglobin, bilirubin, LDH, DAT/Coombs) • Serum creatinine • Thyroid stimulating hormone

Macrocytic Anemia (MCV > 100 L) Initial tests • CBC with reticulocyte count • Peripheral blood ilm • Vitamin B12 level • RBC olate • Liver enzymes and unction (AST, ALT, ALP, GGT, albumin, bilirubin, INR) • Thyroid stimulating hormone

Supplementary tests • Iron studies ( erritin, serum iron, iron saturation, iron binding capacity) • In lammatory markers (ESR, CRP) • Serum protein electrophoresis ± urine protein electrophoresis • Hemoglobinopathy screen • Bone marrow evaluation

Supplementary tests • Bone marrow evaluation

ALP, alkaline phosphatase; ALT, alanine aminotrans erase; AST, aspartate aminotrans erase; CBC, complete blood count; CRP, C-reactive protein; DAT, direct antiglobulin test; ESR, erythrocyte sedimentation rate; GGT, gamma-glutamyl transpeptidase; INR, international normalized ratio; LDH, lactate dehydrogenase; RBC, red blood cell.

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The above case illustrates a classic presentation o acute hemolytic anemia due to a stressor in G6PD de ciency. Patients with less severe G6PD de ciency (WHO class II or III) may have only low-grade hemolysis at baseline, which is exacerbated by triggers including ava beans, oxidant drugs, certain chemicals (eg, naphthalene in moth balls), ever, and/or in ection. Management o acute hemolytic episodes includes discontinuing the o ending trigger and supportive care, which may include RBC trans usion. Prevention o acute hemolytic episodes requires patients and providers to be aware o the underlying G6PD de ciency diagnosis, and amiliar with the list o exposures to avoid. Genetic counseling and testing o relevant amily members is also important, as G6PD de ciency is an X-linked recessive disorder. Individuals with Hemoglobin H disease (alpha thalassemia) can also experience acute worsening o anemia with physiologic stress or exposure to oxidant drugs.

A 52-year-old previously healthy emale presents to the emergency department (ED) with a 3-day history o atigue, dyspnea, jaundice, and “blood” in her urine. Her vital signs are within normal limits. Examination is signi cant or jaundice and petechiae. Initial laboratory testing shows hemoglobin 6.5 g/dL, MCV95 L, reticulocyte count 200 × 109/L, platelet count 8 × 109/L, and white blood cell count 8.2 × 109/L. Peripheral blood lm is signi cant or polychromasia and dense ragments/schistocytes. Creatinine is elevated at 1.64 mg/dL. Coagulation tests are within normal limits. Hemolytic indices show low haptoglobin, positive ree hemoglobin, LDH 1200 U/L, and bilirubin 3.68 mg/dL. Urine shows “3+ blood” on dipstick testing, but no red blood cells on microscopy. This case is an illustration o microangiopathic hemolytic anemia due to thrombotic thrombocytopenic purpura (TTP). Although the classic pentad o TTP includes MAHA, thrombocytopenia, renal ailure, ever, and neurological ndings, a provisional diagnosis o TTP can be made in the presence o MAHA and thrombocytopenia alone. This is to acilitate urgent treatment with plasma exchange due to the high mortality o TTP in the absence o appropriate therapy. Care ul review o peripheral blood lm is essential, with dense ragments or schistocytes, as the de nitive RBC morphological nding in MAHA, alongside the presence o increased reticulocytes. As highlighted in this case, patients (and care providers) may mistakenly identi y the red-colored urine as “hematuria”; while RBCs in the urine should be ruled out, this discoloration is typically due to hemoglobin released by RBC hemolysis/ ragmentation.

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CASE 77-2: ACUTE ANEMIA AND JAUNDICE

o ava beans in his home country o Lebanon, and remembers being told that it was due to an inherited blood disorder.

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and hemodialysis. His hemoglobin decreased rom 11 g/dL on admission to 8 g/dL. There is no bleeding. The MCV is 90 L and reticulocyte count is 50,000/µL (normal range 30-90). The remainder o the CBC and peripheral blood lm are normal. Nutritional and hemolytic investigations are negative. This case illustrates multi actorial anemia commonly encountered in acutely ill-hospitalized patients. In ection and in ammation lead to the production o cytokines, which suppress RBC production through hepcidin-mediated suppression o iron utilization, and suppression o erythropoietin production and activity. Renal ailure contributes to reduced erythropoietin production. Frequent laboratory testing leads to progressive iron losses also contributing to anemia. In stable critical care patients, RBC trans usion should be reserved or patients with hemoglobin concentration less than 7 g/dL.

CASE 77-4: ANEMIA FOLLOWING TRANSFUSION A 78-year-old male with trans usion-dependent myelodysplastic syndrome (MDS) is hospitalized or worsening atigue and dyspnea over the previous week. His last RBC trans usion was 2 weeks ago. On examination his vital signs show BP 115/78, heart rate 105, and oxygen saturation 94% on room air. He appears pale and jaundiced. CBC shows hemoglobin o 5.7 g/dL (baseline maintained above 8 g/dL with RBC trans usion). His platelet count is 67 and WBC 2.3 consistent with his baseline values. Peripheral blood lm shows spherocytes. Total bilirubin is 2.4 mg/dL which is predominantly unconjugated. Direct antiglobulin test is positive or IgG coating the RBCs. A new anti-E RBC alloantibody is identi ed. Delayed hemolytic trans usion reactions (DHTR) result rom the presence o recipient alloantibodies directed against donor RBC antigens. Alloantibodies develop during previous RBC trans usion or prior pregnancy. The antibodies are below the level o detection during the initial antibody screen. Reexposure to donor antigens results in an anamnestic response and increased production o alloantibodies, which bind to donor RBCs and cause hemolysis. DHTRs typically occur within 2 weeks o trans usion and the majority o cases are sel -limited. Patients present with evidence o hemolytic anemia including decreased hemoglobin, reticulocytosis, spherocytosis, elevated LDH, hyperbilirubinemia, positive DAT, and positive antibody screen. Patients with alloantibodies should receive compatible, antigen negative blood.

CASE 77-3: G6PD DEFICIENCY A 65-year-old man with chronic obstructive pulmonary disease (COPD) presents to the ED with acute jaundice 2 days a ter starting moxi oxacin and prednisone or pneumonia with COPD exacerbation. The patient is a ebrile, with oxygen saturation on room air o 95%, blood pressure (BP) o 135/82, and heart rate o 98. He has jaundice and scleral icterus. Chest x-ray shows a consolidation in the right lower lobe. Hemoglobin is 6.2 g/dL, with normal WBC and platelet counts. Peripheral blood lm shows polychromasia, bite cells, and blister cells. Blood lm stained with brilliant cresyl blue is positive or Heinz bodies. Bilirubin is 4.1 mg/dL, reticulocyte count is 362, and haptoglobin level is undetectable. On urther questioning, the patient recalls a prior similar episode in childhood, when he had eaten a large meal

CASE 77-5: APLASTIC CRISIS IN PATIENT WITH SCD A 25-year-old woman with sickle cell disease presents to her internist’s of ce, complaining o increasing atigue over the past week accompanied by headache, runny nose, and muscle aches. She works at a daycare and many o the children have recently been sick with “slapped cheek disease.” Urgent blood tests drawn in the clinic show a hemoglobin o 5.6 g/dL (compared with her baseline hemoglobin o 8.0 g/dL), with normal WBC and platelet counts. Peripheral blood lm shows moderate sickle cells. Reticulocyte count is 8, bilirubin 2.22 mg/dL, and haptoglobin level is undetectable. Blood group and screen is completed 537

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Aplastic anemia due to parvovirus B19 can cause precipitous drop in hemoglobin or patients with chronic hemolytic anemia who rely on a steady, high rate o reticulocytosis to maintain hemoglobin levels. Awareness o this association is critical to rapid, accurate diagnosis. Management is supportive and typically includes RBC trans usion and close monitoring o hemoglobin and reticulocyte counts.

Cold agglutinins are IgM autoantibodies directed against RBC antigens, which bind at low body temperatures (eg, extremities, nose ears) and cause RBC agglutination on the peripheral blood lm and complement-mediated hemolysis. Cold agglutinins are a common sequela o M. pneumonia in ection, particularly in children and young adults. In ectious mononucleosis is also commonly associated with cold agglutinins. Hemolysis in this setting is mild and resolves within 2 to 4 weeks.

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CASE 77-6: AUTOIMMUNE HEMOLYTIC ANEMIA–COLD AGGLUTININS DUE TO MYCOPLASMA PNEUMONIAE

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A 32-year-old woman presents to the ED with ever, cough, atigue, pallor, and jaundice increasing over the past 1 week. Initial evaluation shows BP 110/72, heart rate 118, and regular, oxygen saturation 97% on room air. Lung auscultation reveals rhonchi in the right base and le t mid-zone, and scattered moist rales. Chest x-ray shows di use bilateral in ltrates, most prominent in the lower lobes. Hemoglobin is 101 g/dL, WBC 11.7 × 109 with WBC di erential showing absolute neutrophil count 8.0 × 109, and platelet count 443. Peripheral blood lm shows RBC agglutination and polychromasia. Reticulocyte count is 189. DAT is strongly positive when tested with the monospeci c reagent or C3 (complement). Mycoplasma pneumoniae ELISA test is positive or IgM. The patient is discharged home with a prescription or levo oxacin and instructed to ollow up with his amily physician in 1 to 2 weeks or clinical assessment and repeat CBC.

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Bain B. Diagnosis rom the blood smear. N Engl J Med. 2005;353:498. George JN. Evaluation and management o patients with thrombotic thrombocytopenic purpura. J Intensive Care Med. 2007;22:82. Hébert PC, Wells G, Blajchman MA, et al. A multicenter, randomized, controlled clinical trial o trans usion requirements in critical care. Trans usion Requirements in Critical Care Investigators, Canadian Critical Care Trials Group. N Engl J Med. 1999;340(6):409-417. Koch CG, Li L, Sun Z, et al. Hospital-acquired anemia: prevalence, outcomes, and healthcare implications. J Hosp Med. 2013;8(9):506-512. Otis S, Price EA. Hematology-oncology. Hemoglobinopathies and hemolytic anemias. In: Singh AK, ed. Scientif c American Medicine [online]. Hamilton, ON: Decker Intellectual Properties; 2013. doi:10.2310/7900.1044. http://www.deckerip.com/products/scienti c-american-medicine/. Accessed November 16, 2015. Te eri A. Anemia in adults: a contemporary approach to diagnosis. Mayo Clin Proc. 2003;78(10):1274-1280. Weiss G, Goodnough LT. Anemia o chronic disease. N Engl J Med. 2005;10;352(10):1011-1023.

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CHAP TER

Bleeding and Coagulopathy Meridale V. Baggett, MD Daniel P. Hunt, MD

Key Clinical Questions 1

What are the initial priorities or the patient with severe or li e-threatening bleeding?

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Is the bleeding medically remediable or does it require structural intervention (interventional radiology or surgery)?

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Does the patient have a coagulopathy or a platelet disorder based on history and examination?

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What explains an elevated international normalized ratio (INR), an elevated partial thromboplastin time (PTT), and a low platelet count?

INITIAL BEDSIDE PRIORITIES Initially, the goals or the hospitalist caring or a patient with bleeding should be resuscitation o the unstable patient, control o bleeding, and prevention o urther bleeding. Bedside evaluation o patients with apparent brisk bleeding (gastrointestinal, pulmonary, and postpartum) includes vital sign measurement and assessment or adequate per usion (mentation, capillary re ll, urine output). Interpretation o vital sign measurements should take into account the patient’s baseline blood pressure and any medications that may blunt the heart rate response to bleeding. Evidence o hemorrhagic shock mandates aggressive resuscitation using large bore intravenous access or intravenous uids and blood products. Li e-threatening bleeding events may include intracranial hemorrhage (intracerebral, subdural, epidural, subarachnoid), gastrointestinal hemorrhage, massive hemoptysis, postpartum hemorrhage, and retroperitoneal hemorrhage. Spontaneous intracerebral hemorrhage portends a 25% to 30% in-hospital mortality. Upper gastrointestinal hemorrhage rom varices predicts substantial in-hospital mortality. Similar to management o severe traumatic hemorrhage, the bedside approach should minimize the time between recognition o severe or li e-threatening bleeding and bleeding control. Each diagnostic intervention, including history, physical examination, laboratory testing, and radiographic testing, should have the potential to lead directly to therapeutic intervention. The adage o the trauma surgeon that “the only diagnostic test that is absolutely required be ore operating on the severely injured trauma patient is a type and cross or blood products”emphasizes the absolute ocus on intervention that is required or acute, severe bleeding. In general, control o active bleeding requires a multidisciplinary approach that may involve surgery, interventional radiology, and/or endoscopy. Table 78-1 provides guidance regarding the appropriate consultative services to engage urgently or each o the serious or li e-threatening hemorrhagic problems along with the anticipated approach.

PRACTICE POINT

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How should coagulopathy be managed in the bleeding patient?

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I a coagulopathy is present, what should be done to prepare a patient or an invasive procedure?

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Initial assessment: β-blockers or calcium channel blockers may blunt the usual heart rate response to severe bleeding. Among patients with chronic hypertension, a “normal”blood pressure may actually suggest relative hypotension. Bleeding rom sites that cannot be directly visualized (gastrointestinal, intracerebral, bronchial tree) should prompt great wariness.

SECONDARY HISTORY AND PHYSICAL EXAMINATION FOR BLEEDING DISORDERS Systematic assessment o bleeding disorders requires a working knowledge o normal hemostasis. The two major mechanisms that contribute to clotting in distinctive but interrelated ashion are (1) platelet adhesion, activation, and plugging (“primary hemostasis”) and (2) the coagulation cascade that generates a brin clot (“secondary hemostasis”) with resultant consolidation o the platelet plug. Endothelial injury that exposes the circulating blood to subendothelial tissue actor and collagen activates both clotting mechanisms. Platelets adhere to exposed collagen and to exposed 539

TABLE 78-1 Consultative Approach to Severe Bleeding

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Bleeding Event Spontaneous intracerebral hemorrhage Traumatic brain injury associated hemorrhage -Extradural hematoma -Subdural hematoma -Intracerebral hemorrhage Upper gastrointestinal hemorrhage -Esophageal variceal bleeding -Nonvariceal bleeding -Bleeding peptic ulcer a ter endoscopic treatment Lower gastrointestinal hemorrhage

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Urgent Consultation Neurosurgery Neurosurgery Trauma surgery

Expected Intervention Assessment for surgical intervention.* Assessment for surgical intervention.*

Gastroenterology General Surgery Interventional radiology

Upper gastrointestinal hemorrhage often amenable to endoscopic intervention. Surgery should be involved in most patients with substantial bleeding and should be consulted early.

Gastroenterology General Surgery Interventional radiology General Surgery Interventional radiology (Urology) Obstetrics Thoracic Surgery Interventional radiology Pulmonary

Lower gastrointestinal hemorrhage may require angiography for localization and potential intervention.

Although most patients are managed with conservative approaches and correction of coagulopathy/reversal of anticoagulation, surgical opinion should be obtained early. Ureteral compression may require urologic intervention. Assessment for surgical intervention.* Bronchial artery embolization has a role in stabilizing patients and may be adequate primary treatment.

*Surgical team may request assistance rom Medicine in managing coexistent coagulopathy.

collagen-bound von Willebrand actor. Collagen exposure also activates the platelet, inducing a change in the shape o the platelet to a more irregular orm that enhances adhesion and interaction with other platelets. Activated platelets discharge brinogen, bronectin, von Willebrand actor, platelet actor IV, actor V, and actor VIII, promoting adhesion and aggregation o other platelets. In addition, activated platelets secrete adenosine diphosphate, adenosine triphosphate, and serotonin that also increase platelet activation. Thrombin generated by the coagulation cascade also aggressively activates platelets. Exposure o blood to tissue actor in the subendothelium initiates the coagulation cascade, as depicted in Figure 78-1. This complex interaction o enzymes and co actors generates brin clot that stabilizes the platelet plug. De ciencies o components in the clotting cascade lead to bleeding disorders o varying severity depending on the qualitative and quantitative de ect. Platelet adherence, activation, and aggregation in combination with the explosive production o a brin clot via the coagulation cascade have the potential to induce excessive thrombus ormation. Antithrombin, tissue actor pathway inhibitor, and activated protein C limit the extent o clot propagation. Clotting requires complex interaction o the injured endothelium with platelets and the coagulation cascade. De ects or de ciencies in any o these steps may lead to excessive bleeding or bleeding risk. The history and physical examination are critical components in the evaluation o a patient with a suspected bleeding disorder. It is important to determine i the patient has had signi cant bleeding in response to past hemostatic challenges such as dental extractions, surgery, trauma, or childbirth. Ask about each previous surgery in detail, seeking surgical reports o bleeding, need or trans usion, repeated operations, or potential anatomic contributors to operative or perioperative bleeding. Immediate bleeding suggests primary hemostatic de ects (ie, platelet abnormalities or vascular 540

endothelial abnormalities, such as blood vessel ragility in senile purpura or scurvy), whereas secondary hemostatic de ects (ie, clotting actor abnormalities) typically cause delayed bleeding. Patients with de ects in secondary hemostasis may report a history o hemarthrosis or other deep tissue bleeding. A history o mucosal bleeding usually indicates a de ect in primary hemostasis. Examples o mucosal bleeding include epistaxis, oral bleeding, gastrointestinal or genitourinary bleeding (without a local cause such as malignancy), hemoptysis, and protracted menstrual bleeding. Inquiring speci cally about trans usion requirements, interventions such as suturing or packing, and the need or hospitalization allows estimation o bleeding severity. A history o bleeding since in ancy or early childhood suggests an inherited disorder. Eliciting a amily history o abnormal bleeding can be help ul when considering inherited bleeding disorders and coagulopathies. Lack o such a history, however, is not su ciently sensitive to exclude a hereditary process. Genetic mutations can arise de novo. Variable penetrance may mask disease in relatives. Recessive genetic de ects will not be clinically apparent in relatives with one unctional copy o the gene. Further, sometimes congenital coagulopathy may be inapparent until a major hemostatic challenge. Review o a patient’s medication list should include assessment o prescribed, over-the-counter, and herbal remedies. War arin and heparin products cause iatrogenic de ects in secondary hemostasis. New oral anticoagulants (NOACs) include the direct thrombin inhibitor dabigatran and the anti-Xa inhibitors rivaroxaban and apixaban. The NOACs are commonly used or patients with atrial brillation and venous thromboembolism and pose particular challenges in the management o bleeding. Platelet dys unction induced by aspirin, clopidogrel, prasugrel, ticagrelor, or nonsteroidal anti-in ammatory drugs can contribute to bleeding in the setting o normal platelet counts and coagulation parameters. It is important

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Figure 78 1 Simplified coagulation cascade.

or the hospitalist to determine the timing and dosage o any antithrombotic agents that the patient may have received as this in ormation is key to management. Other medications, such as sul onamides and vancomycin, may contribute to bleeding through drug-induced thrombocytopenia. Quinine-containing beverages (such as tonic water) or medications can also cause thrombocytopenia. Herbal agents (particularly the “g” herbs such as ginseng, garlic, ginko) have been linked with bleeding. Patients with irregular dietary habits, such as hospitalized patients, alcoholics, those with mental illness, and the elderly, are at higher risk or nutrition-related bleeding disorders. Vitamin K de ciency can lead to bleeding through coagulation actor de ciencies. Vitamin C de ciency may mani est as peri ollicular hemorrhages due to impaired collagen synthesis leading to blood vessel ragility. Altered bowel ora due to recent antibiotic use is another cause o vitamin Kde ciency in hospitalized patients.

Examination o the skin and mucous membranes are o central importance in the bedside approach to bleeding disorders. Purpura is caused by the extravasation o blood through the vessel walls into subcutaneous or intracutaneous tissues, resulting in nonblanching skin lesions. Over time, these lesions evolve in color rom red (hemoglobin) to purple (deoxyhemoglobin) to green (biliverdin) to orange (bilirubin). Purpuric lesions are classi ed according to size, which along with location and the presence or absence o preceding trauma can be help ul in identi ying platelet disorders and clotting disorders. Petechiae are nonpalpable purpuric lesions less than 3 mm in diameter. Petechiae should be distinguished rom telangiectasias, which are blanchable. Petechiae are most commonly ound in gravitationally dependent areas, so attention should be directed to the lower legs, ankles, and eet. Petechiae typically result rom platelet de ciency or dys unction, but can also be the result o 541

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increased intravascular pressure, in ammation o capillary beds, or venous stasis. Ecchymoses are nonpalpable purpuric lesions larger than 3 mm in diameter. The size and location o ecchymoses are help ul in determining the type o bleeding disorder causing them. Small, super cial ecchymoses are most commonly due to blood vessel ragility or multiple blood draws in the hospitalized patient, but may also be caused by platelet de ciency or dys unction. Ecchymoses rom ragile blood vessels are usually round or oval with smooth borders and no necrosis. This dif ers rom the ecchymoses seen in disseminated intravascular coagulation (DIC), which o ten show central necrosis surrounded by stellate ecchymoses. Lesions larger than 2 cm or evidence o deep tissue bleeding (eg, hematomas or hemarthroses) indicate a de ect in secondary hemostasis. Large, spontaneous, and centrally located ecchymoses or hematomas are more concerning or underlying pathology than the peripheral bruising a ter trauma seen in patients with normal hemostasis. Mucosal bleeding is generally due to platelet de ciency or dysunction. Epistaxis, conjunctival bleeding, or gingival bleeding may be seen on exam. Hemorrhagic mucosal bullae (“wet purpura”) typically indicate severe platelet de ciency or dys unction, and a higher risk or spontaneous intracranial bleeding.

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Secondary history and examination: Aspirin or other antiplatelet agents are the most common cause o petechiae in hospitalized patients. Bleeding rom a wound that begins several days a ter the initial procedure suggests nutritional de ciency or medicationinduced coagulopathy. Hospitalized patients with limited nutrition or exposure to antibiotics are at risk or vitamin Kde ciency.

LABORATORY TESTING FOR BLEEDING DISORDERS The most use ul initial laboratory assessments or coagulation de ects include the prothrombin time (PT) that is now most commonly reported as the international normalized ratio, the activated partial thromboplastin time (aPTT), and the platelet count. These studies should be obtained in addition to the history and physical examination in an attempt to determine the presence o coagulopathy and to begin to de ne the speci c cause o the de ect.

■ CLOTTING ABNORMALITIES Table 78-2 summarizes the common causes o elevated INR and/ or prolonged aPTT. Prior to considering speci c causes o abnormal INR or aPTT, the clinician should consider possible arti actual causes or these abnormalities. The aPTT and/or INR may be prolonged by incorrect collection o the blood specimen. Collection problems include an inadequate amount o blood in the specimen tube which results in elevated aPTT and INR. Additionally, obtaining the sample above or rom a line that has been ushed with heparin can prolong not only the aPTT but also sometimes the INR. When arti actual elevation is suspected, the assays should be repeated on a specimen obtained by care ul peripheral venipuncture. The measured aPTT may be arti actually prolonged in patients with polycythemia (hematocrit > 55), lipemia, icteric specimens, or hemolyzed specimens. In these situations, the clinical laboratory can be help ul in determining the appropriate approach. To e ciently assess the etiology o an elevated INR or aPTT, the next step a ter exclusion o arti actual abnormality is to care ully 542

TABLE 78-2 Clinical Clues to Coagulation Defects

Etiology

Timing o bleeding post trauma or surgery Characteristic bleeding sites Physical exam indings

Primary Hemostasis Defect Platelet de iciency or dys unction Vascular endothelial abnormalities Immediate

Secondary Hemostasis Defect Coagulation actor abnormalities

Mucosal

Deep tissue or hemarthrosis Large, central, spontaneous ecchymosis Hemarthrosis

Petechiae Epistaxis

Delayed

review medications or the presence o anticoagulants (vitamin K antagonists including war arin, heparins, or direct thrombin inhibitors). Systemic diseases that might prolong clotting time should be considered on the basis o the history and examination. For unexplained elevated INR or prolonged aPTT, a mixing study with normal plasma may help dif erentiate between a actor de ciency and the presence o an inhibitor. I the aPTT corrects in a mixing study, then speci c assays or actors in the intrinsic pathway (Figure 78-1) are indicated. Correction o a prolonged prothrombin time in the mixing study implies de ciency o prothrombin, brinogen, or actors V, VII, or X. For a hospitalized patient with an elevated INR due to actor de ciencies, the most common causes are war arin or vitamin K de ciency due to antibiotics and poor nutritional intake. Additionally, patients who receive large-volume RBC trans usions may develop low levels o remaining clotting proteins even i they receive concurrent resh rozen plasma (FFP) along with their RBC trans usions at the time o surgery. Each unit (250 mL) o packed RBCs trans used results in approximately a 5% decrease in the concentration o clotting proteins, and the hal -li e o FFP is hours in contrast to RBCs which are in the order o weeks. For malnourished surgical patients who received signi cant trans usions, they may not make su cient innate clotting actors quickly enough to make up or the recent blood loss. I the mixing study shows a persistent prolongation o aPTT, this implies the presence o an inhibitor o the aPTT pathway. These inhibitors include un ractionated heparin, direct thrombin inhibitors (lepirudin, argatroban), lupus anticoagulant, or speci c actor inhibitors including inhibitors o actor VIII or actor V. Additional studies that allow the laboratory to determine the presence o heparin or a direct thrombin inhibitor include the thrombin time (TT) and reptilase time. Either class o drugs will prolong the TT, but demonstrate a normal reptilase time. Persistent prolongation o the prothrombin time despite mixing with normal serum implies an inhibitor o the PT pathway and generally is associated with prolongation and inhibition o the aPTT. These inhibitors include actor V inhibitors, direct thrombin inhibitors, excess heparin in the laboratory specimen, or, less commonly, a lupus anticoagulant. I the examination demonstrates petechiae or there is signi cant mucosal bleeding, a quantitative or qualitative abnormality o platelets should be considered. There are many potential causes o thrombocytopenia in hospitalized patients. Table 78-3 provides a ramework or considering a low platelet count. Assessment o platelet unction is more di cult, although the medication history is o ten revealing as the most common causes o petechiae or platelet

H A P T E R 7 8 B l e e d

Consumptive Processes Thrombotic thrombocytopenia purpura (TTP) Hemolytic uremic syndrome (HUS) Sepsis Eclampsia/HELLP syndrome Disseminated intravascular coagulation Hypersplenism

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Immune-Mediated Processes Immune thrombocytopenia purpura (ITP) Drugs (eg, heparin) In ections Post-trans usion

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Increased Platelet Destruction

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von Willebrand disease, uremia, liver disorders, paraproteinemias, chronicmyeloproli erative disorders) may cause prolongation o the bleeding time (Table 78-4). A prolonged bleeding time, even assuming technical reliability, is a very nonspeci c nding. Additionally, normal bleeding times do not assure hemostasis with invasive procedures, while prolonged bleeding times are not necessarily associated with excessive hemorrhage. A 1998 position statement rom the College o American Pathologists and the American Society o Clinical Pathologists concluded that the bleeding time test ailed as a screening test. Many hospital laboratories no longer of er the bleeding time test. Automated platelet unction testing may provide better insight when patients are suspected to have de ects

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dys unction among hospitalized patients are antiplatelet medications. See Chapter 171 (Platelets). Although the bleeding time was traditionally used as an initial screening test or primary hemostasis, recent guidelines argue against its use. The test requires a small incision o the skin ollowed be measurement o time to clot ormation. Technical variables that make reproducibility o the test challenging include direction o the incision, exercise, cuf pressure on the tested arm, previous testing, patient anxiety, local edema, and excessive wiping o the incision make reproducibility o the test challenging. Numerous medications (including aspirin, nonsteroidal anti-in ammatories, antibiotics, calcium channel blockers) and clinical conditions (including

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Decreased Platelet Production Other Processes Affecting Marrow Processes Production Myeloproli erative disorders Drugs Aplastic anemia B12 or olate de iciency Radiation In ections (such as HIVor parvovirus) Cirrhosis (decreased thrombopoietin)

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TABLE 78-3 Causes of Thrombocytopenia

TABLE 78-4 Causes of Abnormal INR or aPTT Test Result INR aPTT Elevated Normal

Normal

Prolonged

Elevated

Prolonged

Causes Inherited Acquired Factor VII de iciency War arin or other coumarins (such as rat poison) Neworal anticoagulants Liver disease Vitamin Kde iciency Acquired actor VII de iciency Inhibitor o actor VII De iciency o actors VIII, IX, or XI Heparin De iciency o actor XII, prekallikrein, or Low molecular weight heparin (particularly high-molecular-weight kininogen (HMWK) when dosed excessively) (associated with abnormal labs but not bleeding) Neworal anticoagulants von Willebrand disease Inhibitor o actors VIII, IX, XI, or XII Acquired von Willebrand disease Lupus anticoagulant Liver disease De iciency o prothrombin, ibrinogen, or actors Vor X Disseminated intravascular coagulation Dys ibrinogenemia Heparin Combined actor de iciencies Supratherapeutic war arin, or other coumarins Vitamin Kde iciency Combined war arin and heparin Inhibitor o prothrombin, ibrinogen, or actor Vor X Direct thrombin inhibitors (including dabigatran) Neworal anticoagulants (rivaroxaban, apixaban) Primary amyloidosis ( actor X de iciency)

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in primary hemostasis, but have normal PT, PTT, and platelet count. The Platelet Function Analyzer (PFA-100) has been adopted by many laboratories and has received considerable attention in the literature. This test stimulates platelets through interaction with a membrane coated with collagen and either adenosine diphosphate or epinephrine and then measures the time required or the platelets to close an aperture o the membrane. This is thought to simulate the adhesion and aggregation o platelets in vivo. A systematic review ound that the sensitivity o the PFA-100 system is 82% to 89%, while the speci city is 67% to 86% or detection o a de ect in primary hemostasis as determined by more comprehensive platelet unction testing. For patients who are highly suspected o having a disorder o platelet unction, a negative PFA-100 test would not absolutely exclude a unctional problem. In these cases, consultation with a hematologist and with the clinical laboratory is advisable.

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Laboratory evaluation: I the INR and/or aPTT are unexpectedly elevated, the studies should be repeated to exclude arti act. Mixing studies are a key step in determining whether the apparent de ect is a de ciency or an inhibitor o actor(s) in the coagulation pathway. Bleeding time is no longer used to assess platelet unction.

TREATMENT OF COAGULOPATHY IN THE BLEEDING PATIENT The bleeding patient should be assessed or concomitant acute or chronic de ects in either primary or secondary hemostasis so that appropriate corrective treatment can be administered alongside hemodynamic support and trans usion o red blood cells in anticipation o any necessary structural interventions. Table 78-5 summarizes treatment options to address hemostasis de ects in bleeding patients.

It is use ul to assess the degree o bleeding using the WHO bleeding grades when deciding interventions or coagulopathies. The grades are as ollows: Grade 0 = no bleeding; Grade 1 = petechiae, ecchymosis, mucosal bleeding; Grade 2 = gross bleeding, including melena, hematemesis, hematuria, or hemoptysis; Grade 3 = bleeding that requires red blood cell trans usion; and Grade 4 = retinal bleeding with visual impairment, intracranial bleeds, and li e-threatening bleeds (massive gastrointestinal hemorrhage, retroperitoneal hemorrhage, massive hemoptysis). For hemorrhage that is considered WHO Grade 2 or greater, platelet trans usions are indicated i thrombocytopenia is present although the speci c threshold or trans usion should be individualized. In general, the target or the platelet count a ter trans usion should be greater than 50,000. Trans usion o platelets or patients with suspected platelet dys unction is reasonable in the setting o substantial bleeding, although there are no readily available laboratory parameters to guide management. Recent guidelines emphasize a pre erence or use o prothrombin complex concentrates (PCC) in the management o major bleeding in patients with vitamin K de ciency or war arin therapy. PCC contains concentrated vitamin-K-dependent coagulation actors, does not require thawing, and is administered in a relatively small volume. Three- actor PCC that is available in the United States contains actors II, IX, and X (re er to Figure 78-1), while our- actor PCC contains actors II, VII, IX, and X. Emergent reversal o war arin should be addressed with weight-based dosing o PCC along with IVvitamin K. Fresh rozen plasma (FFP) contains plasma proteins including coagulation actors. It may be used or bleeding patients with vitamin K de ciency or war arin therapy although it is considered suboptimal and should only be used i PCC is not available. FFP may also be used to manage bleeding and coagulopathies associated with liver disease, acute DIC with a treatable trigger, massive trans usion, and acquired de ciencies o single coagulation actors. Laboratory parameters that would prompt use o FFP to address bleeding in any o these conditions include signi cantly increased prothrombin time, INR, or aPTT, although massive red blood cell trans usion o greater than one blood volume should prompt consideration o FFP

TABLE 78-5 Management of Coagulopathy in the Bleeding Patient Defect Primary Hemostasis Thrombocytopenia or platelet dys unction (ie, NSAID use)

Secondary Hemostasis Elevated PTT with unknown actor de iciency

Vitamin Kde iciency (ie, nutritional de iciency or war arin use)

Treatment

Suggested Initial Dose

Expected Response

Potential Complications

Platelet trans usion

6 pack (4-6 whole blood derived units pooled) or one apheresis unit

30-60,000/µL increase in platelet count

In ection Hemolytic trans usion reaction Trans usion-related acute lung injury (TRALI)

Fresh rozen plasma

10-15 mL/kg

Not well de ined

Vitamin K* Prothrombin complex concentrate Fresh rozen plasma

10 mg IV Dosage varies dependent on manu acturer 10-15 mL/kg

INR improvement within 4-6 h Emergent reversal o vitamin Kantagonists Not well de ined

In ection Hemolytic trans usion reaction TRALI Volume overload Anaphylaxis Overcorrection and war arin resistance Potential risk o venous and arterial thrombosis See above

*For serious bleeding, administer prothrombin complex concentrate concurrently or immediate replacement o vitamin-K-dependent coagulation actors.

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INVASIVE PROCEDURES IN THE COAGULOPATHIC PATIENT Hospitalized patients are requently subjected to invasive procedures or both diagnostic and therapeutic purposes, and hospitalists requently consult on patients prior to surgical procedures. The potential or bleeding complications plays a central role in the discussion o risks and bene ts o proposed procedures, and despite a lack o highquality evidence to support indiscriminant preprocedural coagulation testing, it is common practice or patients to have coagulation testing in anticipation o most procedures. However, identi ying patients at high risk or bleeding requires a clinical history and should not rely on laboratory testing alone. PT and PTT tests may be insensitive to rare but clinically important bleeding disorders. For example, patients with actor XIII de ciency (who usually have a positive

C H A P T E R 7 8 B l e e d i n g a n d C o a g u l o

The new oral anticoagulants (NOACs) present assessment and management challenges or practicing hospitalists. These agents have also been called novel oral anticoagulants or target speci c oral anticoagulants (TSOACs). Dabigatran is a direct thrombin inhibitor that is excreted by the kidneys. Although there are no readily available reliable laboratory tests or the anticoagulant ef ects o dabigatran, a normal aPTT and normal thrombin time suggest that high levels are not present in the bleeding patient. Hemodialysis would be expected to accelerate clearance o dabigatran, although this can be challenging to employ in an acutely ill, bleeding patient. For patients with ongoing li e-threatening bleeding, options would include PCC, activated PCC (APCC), or recombinant Factor VIIa (rFVIIa), although these recommendations are based on case reports, animal studies, and expert opinion. A recent clinical trial o idarucizumab, a monoclonal antibody ragment with very high a nity or binding dabigatran, showed very rapid reversal o anticoagulant ef ect and may become standard o care or patients with li e-threatening hemorrhage in the setting o dabigatran. Rivaroxaban and apixaban are oral actor Xa inhibitors. Both agents are tightly protein bound and there ore are not removed by dialysis. There are no speci c pharmacologic countermeasures or these agents, so or the majority o bleeding patients, the best approach is cessation o the drug and addressing the source o bleeding. For ongoing li e-threatening bleeding, PCC, APCC, or rFVIIa could be considered. However, both APCC and rFVIIa incur an increased risk o thrombosis. Hospitalists should strongly consider obtaining hematology consultation or patients receiving NOACs when aced with bleeding or when considering periprocedural or perioperative risks or these patients.

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Correction o coagulopathy: Patients with severe bleeding and suspected platelet dys unction (eg, rom antiplatelet agents) should be considered or platelet trans usion despite normal platelet counts. FFP and platelet trans usions are associated with a higher risk o trans usion-related acute lung injury than red blood cell trans usions.

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bleeding history) may have normal PT and PTT tests, but experience li e-threatening surgical bleeding. Current recommendations rom the British Committee or Standards in Hematology are to obtain a bleeding history in all patients undergoing invasive procedures or surgery, including bleeding ollowing prior trauma or surgery, a amily history o bleeding, and the use o prescription and nonprescription medications that predispose to bleeding. Selected patients should undergo coagulation testing. Patients who may bene t rom coagulation testing include those with a positive bleeding history, evidence o systemic disease that may af ect coagulation (eg, liver disease), or risk actors or malabsorption or malnutrition. Patients planned or procedures associated with a higher risk o morbidity and mortality rom bleeding complications (eg, intracranial, neurosurgical) typically have preoperative coagulation testing. Patients with abnormal bleeding histories or other clinical indications warrant directed diagnostic testing guided by their clinical eatures and may require hematology consultation to help guide urther workup and the plan or correction prior to undergoing procedures. I diagnostic testing reveals prolongation o the PT, options or correction will be dictated by the underlying etiology. Those with nutritional de iciencies typically respond to administration o vitamin K. While oral administration o vitamin K is slower to take ef ect, there is less risk o anaphylaxis which has been associated with intravenous administration o vitamin K. Subcutaneous vitamin K works more slowly than oral vitamin K, and in one meta-analysis was similar to placebo in treating excessive anticoagulation. Although widely practiced, the prophylactic use o FFP or patients with prolonged PT undergoing procedures lacks su cient evidence to support or re ute its e cacy and the potential hazards o trans usion are well documented. In patients with minimally prolonged PT, trans usion o FFP may have little ef ect on the PT, and the ef ects may be transient i the patient is not provided with substrate (vitamin K) to generate more clotting actors. Many inpatient procedures are perormed by specialists and interventional radiologists, and the pre erence and com ort o the operator will largely drive the preprocedural testing and trans usion practice. See Chapter 43 (Hemostasis).

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even i coagulation parameters are unknown. FFP carries a substantial risk o trans usion-related acute lung injury (TRALI) and a number o studies caution about its overuse, particularly or patients with minimally elevated INR (up to 1.7) or aPTT. Oral vitamin Kis the preerred route o administration or most patients with mildly elevated INR in the absence o li e-threatening hemorrhage.

PRACTICE POINT

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Preprocedure evaluation or coagulopathy: Obtaining a bleeding history rom a patient may help uncover coagulopathies not evident on routine testing. Oral vitamin Kis the pre erred treatment o nutritionrelated coagulopathy in patients planned or nonemergent procedures. I possible, procedures should be delayed to allow clearance o the anticoagulant ef ect o NOACs.

CONCLUSION The approach to a bleeding patient starts with emergent resuscitation i required, identi cation o the bleeding site, evaluation or the presence o a coagulopathy (initially PT, INR, aPTT, and platelet count), and management o bleeding which may require specialty consultation. A stepwise approach begins with a ocused history and physical examination. The cause o a surgical patient’s elevated INR and bleeding are most likely due to a number o actors: (1) poor nutrition causing relative vitamin Kde ciency, (2) exposure to broad spectrum antibiotics, (3) exposure to anticoagulants, and/or (4) in cases o major trauma requiring recent large-volume RBC trans usion, low levels o remaining clotting proteins. Other considerations or an elevated INR in the absence o war arin include: severe liver disease (history o alcohol use, abnormal liver unction tests, clinical signs o cirrhosis, 545

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preoperative elevation o INR), acquired actor VIII inhibitors or actor VIII de ciency, von Willebrand disease causing some degree o actor VIII de ciency, DIC or signi cant renal or hepatic insu ciency resulting in supratherapeutic doses o low molecular weight heparin. Evaluation o thrombocytopenia should include review o the peripheral smear. The timing o onset o thrombocytopenia is a valuable clue regarding its possible etiologies. In general, patients with low platelet counts or documented platelet unction abnormalities who are bleeding are likely to bene t rom platelet transusions. However, unlike correction o anemia, not all causes o thrombocytopenia may be sa ely treated with the trans usion o platelet products. Conditions associated with immune destruction o platelets (such as immune thrombocytopenia or heparin induced thrombocytopenia) or microangiopathic hemolysis (thrombotic thrombocytopenic purpura) can be dangerously aggravated by platelet trans usions. See Chapter 77 (Anemia) and Chapter 172 (Bleeding Disorders).

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SUGGESTED READINGS

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Chee YL, Craw ord JC, Watson HG, Greaves M. Guidelines on the assessment o bleeding risk prior to surgery or invasive procedures. British Committee or Standards in Haematology. Br J Haematol. 2008;140(5):496-504.

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Crowther M, Crowther MA. Antidotes or novel oral anticoagulants: current status and uture potential. Arterioscler Thromb Vasc Biol. 2015;35:1736-1745. De Simone N, Sarode R. Diagnosis and management o common acquired bleeding disorders. Semin Thromb Hemost. 2013;39:172-181. Hurwitz A, Massone R, Lopez BL. Acquired bleeding disorders. Emerg Med Clin North Am. 2014;32:691-713. Kamal AH, Tef eri A, Pruthi RK. How to interpret and pursue an abnormal prothrombin time, activated partial thromboplastin time, and bleeding time in adults. Mayo Clin Proc. 2007;82(7):864-873. Lippi G, Franchini M, Montagnana M, Favaloro EJ. Inherited disorders o blood coagulation. Ann Med. 2012;44:405-418. Makris M, Van Veen JJ, Tait CR, Mum ord AD, Laf an M. British Committee or Standards in H. Guideline on the management o bleeding in patients on antithrombotic agents. Br J Haematol. 2013;160:35-46. Rossaint R, Duranteau J, Stahel PF, Spahn DR. Nonsurgical treatment o major bleeding. Anesthesiol Clin. 2007;25(1):35-48, viii. Tanaka KA, Key NS, Levy JH. Blood coagulation: hemostasis and thrombin regulation. Anesth Analg. 2009;108(5):1433-1446.

79

CHAP TER

Chest Pain Kittane S. Vishnupriya, MBBS Arjun S. Chanmugam, MD, MBA

Key Clinical Questions 1

What signs and symptoms point to a serious cause o cardiogenic chest pain?

2

What key historical elements will help to narrow the di erential diagnosis?

3

What studies should be ordered to evaluate a patient presenting with suspected cardiac ischemia?

INTRODUCTION According to the 2006 National Hospital Ambulatory Medical Care Survey, 6,392,000 patients presented to emergency departments (ED) with a chie complaint o chest pain or related symptoms. O those, 1,976,000 patients were admitted to the hospital, with a mean length o stay o 3.7 days. Chest pain was the principal admitting diagnosis in 5.4% o all admitted patients. Because morbidity and mortality is high i clinicians “miss” a cardiac presentation o chest pain, a signi cant portion o these admissions are speci cally or the purpose o ruling out myocardial ischemia or in arction. In one study o patients presenting to an emergency department with complaints consistent with cardiac ischemia, 17% ultimately had cardiac ischemia, while 27% had stable angina or other cardiac conditions. Fi ty- ve percent had noncardiac conditions diagnosed as the cause o their symptoms. The wide di erential diagnosis or this heterogeneous group o patients includes nonischemic li e-threatening etiologies as well as more benign causes. Despite the ocus on cardiac causes, in this study, 2.1% o the patients with acute myocardial in arction were erroneously discharged; this gure and the concern it generates may play prominently in the low threshold to admit patients with chest pain. Chest pain also occurs in patients already admitted to the hospital or other reasons. These patients have already su ered some degree o physical decompensation and an occurrence o chest pain may indicate illness, a complication o hospitalization, or a patient’s response to a very stress ul situation. The hospitalist must evaluate the possibility o an immediate li e-threatening event, consider the entire di erential o possible etiologies, and integrate this in ormation with the patient’s prior clinical diagnoses and course. The ocus o this chapter will be on the initial evaluation o patients presenting with chest pain, speci cally targeting the investigation o cardiac ischemia in those patients. BEDSIDE APPROACH

■ INITIAL RAPID ASSESSMENT The initial evaluation o a patient reporting chest pain requires the rapid identi cation and treatment o any li e-threatening conditions. These include the ve “do-not-miss” causes o chest pain: (1) aortic dissection, (2) acute myocardial in arction (MI), (3) pulmonary embolism (PE), (4) pneumothorax, and (5) esophageal rupture (Table 79-1). The electrocardiogram (ECG) is one o the most important screening tests or early risk strati cation and is o ten per ormed at the point o triage as one o the “vital signs.” All potentially unstable patients with chest pain should have an intravenous line, supplemental oxygen, and a cardiac monitor placed as soon as possible. This can be accomplished even be ore the arrival o the physician at the patient’s bedside. Empiric treatment with aspirin and sublingual nitroglycerin should be given i cardiac chest pain is suspected unless there are speci c contraindications. An initial assessment should include a review o the ECG, analysis o current vital signs, and a targeted history and physical examination. A stat portable chest radiograph should be ordered. With this in ormation, patients can be assigned to one o three classes which suggest high, intermediate, or low likelihood o acute coronary syndrome (ACS) which is described in detail below.

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TABLE 79-1 Life-Threatening Causes of Chest Pain Risk Factors Characteristic Findings Diagnostic Testing Hypertension, connective tissue New diastolic murmur, Computed tomography, disease, vasculitis, prior heart upper-extremity pulse de icit, magnetic resonance or valvular surgery, Turner neurologic complications o imaging, transesophageal syndrome, crack cocaine use, stroke echocardiography, angiography cardiac catheterization Special considerations: Aortic dissection may be di icult to diagnose, but patients will most commonly present with chest pain; syncope may occur at the time o symptom onset. Dissections may be classi ied as Stan ord type A (involving the ascending aorta) or type B (all others). In one study, 72.7% o patients reported chest pain, 90.6% reported severe or worst pain ever, and 84.8% had abrupt onset. Aortic insu iciency murmur was noted in 31.6% and pulse de icit was noted in 15.1%. Chest radiograph showed widened mediastinum in 61.6%, and ECGs were less help ul, being normal in 31.3%.* Medical treatment is initially indicated or type B dissections with strict blood pressure control (betablockade and nitroprusside). Given the high risk or li e-threatening complications such as tamponade, aortic regurgitation, and myocardial in arction, type A dissections are treated as surgical emergencies. Myocardial infarction Age over 55, tobacco use, S4 or S3 gallop, vomiting, Electrocardiography, cardiac amily history o coronary diaphoresis, Levine sign biomarkers artery disease, diabetes, ( ist over center chest, low hypercholesterolemia, predictive value) hypertension Special considerations: The diagnosis o ST-segment elevation myocardial in arction should be readily made rom a 12-lead ECG and requires urgent intervention to improve survival. These patients will bene it rom standard medical therapy as well as reper usion. According to the 2007 ACC/AHA ocused update on the management o patients with ST-elevation myocardial in arction, patients with acute STEMI will bene it rom primary percutaneous intervention with a goal door-to-balloon time o 90 min. These guidelines are directed toward patients presenting to the hospital with STEMI, but may also help to decide when to trans er inpatients who develop STEMI during hospitalization. Pulmonary embolism Immobilization, recent surgery, Dyspnea, pleuritic pain, cal or Computed tomography, stroke, paralysis, prior venous leg pain or swelling, jugular ventilation-per usion scan, thromboembolism, malignancy, venous distention pulmonary angiography recent central venous instrumentation Special considerations: Thrombolytic therapy or submassive pulmonary embolism (PE) is a controversial treatment modality. It has been advocated or patients with evidence o right ventricular dilation or hypokinesis on echocardiography, but this indication or use is generally not widely accepted. Thrombolysis or cardiac arrest rom PE has been success ul in case reports, but does not seem to be help ul in cases o pulseless electrical activity.§ Thrombolytic regimens or PE range rom 2 to 24 h in usions. For imminent or actual cardiac arrest, a bolus therapy is indicated. One such regimen is tPA, 0.6 mg/kg over 2 min. Pneumothorax Pneumocystis jirovecii, Decreased breath sounds, Chest radiography, computed tuberculosis, chronic obstructive hyperresonant percussion, tomography pulmonary disease, Mar ans, distended neck veins, tracheal amilial, mechanical ventilation, deviation smoking, cystic ibrosis Special considerations: O all emergency diagnoses, the only one that is immediately reversible is a tension pneumothorax. Needle decompression involves placing a 14-gauge angiocath in the second or third intercostal space in the midclavicular line. In a study o trauma patients with computed tomography scans o the chest, the mean chest wall thickness studied averaged 4.24 cm at this location, and almost a quarter o patients had chest walls thicker than 5 cm.¶ There ore, one should use the longest catheter possible. Alternatives include using a spinal needle or rapid tube thoracostomy. Esophageal rupture Esophageal instrumentation, “Hammans sign” (mediastinal Cervical and chest radiography, orce ul emesis, ulcers or crunching sound), subcutaneous computed tomography, esophagitis emphysema, odynophagia, contrast esophagography hoarseness (cervical rupture) Special considerations: More than hal o all cases o esophageal rupture occur as a complication o medical procedures that involve instrumentation o the esophagus, so knowledge o the inpatient course is paramount.** Spontaneous ruptures classically occur a ter orce ul vomiting, but may also be associated with ingestion o caustic substances or pills, eosinophilic esophagitis, Barretts esophagitis, or ulcers.

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Diagnosis Aortic dissection

*Hagan PG, Nienaber CA, Isselbacher EM, et al. The International Registry o Acute Aortic Dissection (IRAD): new insights into an old disease. JAMA. 2000;283:897. ? Antman EM, Hand M, Armstrong PW, et al. 2007 ocused update o the ACC/AHA 2004 Guidelines or the Management o Patients With ST-Elevation Myocardial In arction: a report o the American College o Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Group to Review New Evidence and Update the ACC/AHA 2004 Guidelines or the Management o Patients With ST-Elevation Myocardial In arction). J Am Coll Cardiol. 2008;51:210-247. § Abu-Laban RB, Christenson JM, Innes GD, et al. Tissue plasminogen activator in cardiac arrest with pulseless electrical activity. N Engl J Med. 2002;346:1522. ¶ Givens ML, Ayotte K, Mani old C. Needle thoracostomy: implications o computed tomography chest wall thickness. Acad Emerg Med. 2004;11(2):211-213. **Pasricha P, Fleischer D, Kalloo A. Endoscopic per oration o the upper digestive tract: A review o their pathogenesis, prevention and management. Gastroenterology. 1994;106:787.

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PRACTICE POINT

•

All patients with chest pain should be rst evaluated or stability and possibility o any li e-threatening conditions.

■ HISTORY The history remains important in initial risk strati cation because objective evidence including a diagnostic ECG is only present in a minority o patients. Once emergency conditions have been ruled out or stabilized, a targeted history can be used to identi y and prioritize a list o di erential possibilities (Table 79-2). Classic symptoms o angina/cardiac ischemia include chest heaviness, pressure, tightness, or burning (sometimes with vigorous denial o pain), provocation by physical or emotional stress or cold, relie by rest, radiation to neck, jaw, or shoulder, duration >2 minutes and 20 minutes could suggest myocardial in arction), dyspnea, nausea/vomiting, diaphoresis, presyncope, and palpitations. However, some recent studies have shown that a signi cant proportion o patients with STEMI (ST elevation myocardial

C H A P T E R 7 9 C h e s

When it comes to initial diagnosis o ACS (acute coronary syndrome), risk actor evaluation does play a role and is help ul in strati ying patients or appropriate workup. Age over 55 years, amily history o coronary artery disease (CAD), known CAD, vascular disease (cerebrovascular, peripheral vascular disease), diabetes mellitus, hypercholesterolemia, hypertension, and tobacco use are recognized as risk actors or CAD. Absence o risk actors does not rule out ACS. Given the high prevalence, morbidity, mortality, and liability issues surrounding the diagnosis o ACS, risk actors are always used in conjunction with clinical evaluation and diagnostic techniques in highly e cient pathways which are urther detailed later in this chapter.

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Other Esophageal rupture Mallory-Weiss tear Esophageal spasm Pancreatitis Biliary tract disease Costochondritis Musculoskeletal injury Peptic ulcer disease Gastritis/ esophagitis/re lux Herpes zoster Mediastinitis Psychogenic/ psychosomatic

a

Pulmonary Pneumothorax Pulmonary embolism Pleuritis/serositis Pneumonia Cancer Sarcoidosis

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TABLE 79-2 Differential Diagnosis of Chest Pain

in arction) and NSTEMI (non-ST elevation myocardial in arction) have either atypical chest pain (pleuritic, stabbing, or reproducible chest pain) or no chest pain at all. It should be noted that relie o chest pain with nitroglycerin does not predict ACS. While history alone is insu cient to rule out cardiac ischemia, it may be used in combination with exam and ECG testing, to identi y patients who are at low risk or cardiac ischemia (Table 79-3).

THE PHYSICAL EXAMINATION The physical examination is o ten normal in patients with chest pain, even when serious pathology is present. However, certain signs may be help ul or risk strati cation and or determining symptom etiology. Overall appearance o the patient combined with vital signs including pulse oximetry should be noted early in the assessment. Tachycardia and hypotension are ominous signs in the patient with chest pain and may require intervention to prevent cardiovascular collapse. Tachypnea may be subtle; the clinician should measure this vital sign independently i suspicion is high despite a normal documented respiratory rate, as it is one o the most common signs o pulmonary embolism (PE). New ever may direct the workup toward in ectious etiologies but low-grade ever is a nonspeci c nding and may also be associated with PE, myocardial in arction (MI), pneumonia, and pericarditis. New hypoxia is a clue to either cardiac (pump insu ciency with heart ailure) or serious pulmonary pathology. It is important to per orm cardiac auscultation in a quiet room and ask the patient to lean orward. Using the diaphragm o the stethoscope, the examiner should listen or regurgitant murmurs and

TABLE 79-3 Likelihood that Signs and Symptoms Represent an ACS Secondary to CAD Feature

History

Examination ECG

Biochemical markers

High Likelihood Any o the ollowing

Intermediate Likelihood Absence o any high likelihood eatures and presence o any o the ollowing Chest pain or le t arm discom ort as Chest or le t arm pain or chie complaint reproducing prior discom ort as chie symptom; documented angina; known history age >70 y; male sex; o CAD, including MI diabetes mellitus Transient MR, hypotension, Peripheral vascular disease pulmonary edema or rales New ST deviation (≥0.05 mV) or Fixed Q waves; abnormal T-wave inversion (≥0.2 mV) with ST segments not documented symptoms to be new Elevated troponin or CK-MB Normal

Low Likelihood Absence o high or intermediate eatures but may have the ollowing Probable ischemic symptoms in absence o any o the intermediate likelihood characteristics; recent cocaine use Chest discom ort reproduced by palpation T-wave lattening or inversion with dominant R waves; normal ECG Normal

ACS, acute coronary syndrome; CAD, coronary artery disease; CK-MB,MB raction o creatine kinase; MI, myocardial in arction; MR, mitral regurgitation. Reproduced, with permission, rom Anderson JL, Adams CD, Antman EM, et al. ACC/AHA 2007 guidelines or management o patients with unstable angina/ non-ST elevation myocardial in arction. J Am Coll Cardiol. 2007;50(7):e1-e157.

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pericardial riction rubs. The nding o a new systolic mitral insu ciency murmur might indicate myocardial ischemia, a f ail mitral leaf et, or decompensated heart ailure and as such, puts the patient in a high likelihood category. A new murmur o tricuspid insu ciency might signal right ventricular overload rom PE. A diastolic murmur may ref ect acute aortic insu ciency and aortic dissection. Any new murmur, especially in the presence o ever, may signi y endocarditis. See Chapter 255 (Diseases o the Aorta) and Chapter 189 (In ective Endocarditis). Other examination ndings o evidence o extracardiac vascular disease places the patient at intermediate risk o ACS. Chest pain reproduced by palpation is less likely to be rom ACS but does not rule it out completely.

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ST segment elevation: The ESC/ACCF/AHA/WHF committee or the de nition o myocardial in arction established speci c ECG criteria or ST-segment elevation myocardial in arction including 2 mm o ST-segment elevation in ECG leads or men (1.5 mm or women) and greater than 1 mm in other leads. The elevations must be present in at least two contiguous leads, corresponding to a speci c arterial territory. Although controversial, symptomatic patients with “new” or “presumed new” le t bundle branch block (LBBB) should be considered as high risk similar to STEMI but need not be rushed to cardiac catheterization as was recommended previously. This is in light o recent studies which revealed that only a small number o these patients with LBBB had MI and two-thirds o these patients were discharged with alternative diagnoses. Many patients will have alternate causes o ST-segment elevation (benign early repolarization, le t ventricular hypertrophy or aneurysm, pericarditis, hyperkalemia), so experience interpreting ECGs, obtaining serial ECGs, and comparison with old ECGs is critical. In pericarditis, the lack o regional ischemic changes (ie, di use rather than localized ST elevations), PR depression, as well as a suggestive history and cardiac examination may help distinguish pericarditis rom MI. See Chapter 130 (Myocarditis, Pericardial Disease, and Cardiac Tamponade). Bundle branch block and paced rhythms make ECG interpretation challenging. The Sgarbossa criteria assign points to signi cant ECG ndings in the presence o a le t bundle branch block: concordant ST-segment elevation o 1 mm or more in any lead ( ve points), ST-segment depression o 1 mm or more in leads V1, V2, or V3 (three points), discordant ST-segment elevation o 5 mm or more (two points). A score o at least three is associated with high speci city or myocardial in arction but low sensitivity. In patients with LBBB or paced rhythms, the nding o ST-segment elevation ≥5 mm in leads with a negative QRS complex is highly speci c or myocardial in arction. Identi cation o in erior wall myocardial in arction should be ollowed by examination or evidence o posterior wall involvement (V1 ST depression), conduction disturbance (Wenckebach, bradycardia, or complete heart block), and right ventricular in arction (right-sided ECG, lead rV4). ST segment depression: ST-segment depression (0.5 mm or greater) predicts increased risk o myocardial ischemia. The greater the extent o depression, the higher the risk o MI and 550

death. In addition, ST depression in ≥2 mm in some precordial leads (V1–V4) may indicate transmural posterior injury; multilead ST depression with coexistent ST elevation in lead aVR has been described in patients with le t main or proximal le t anterior descending artery occlusion. Posterior leads may help di erentiate the patient with anterior ST-segment depression who has ischemia rom the patient who has an acute posterior wall MI. T wave inversion: These indicate lower risk than ST depressions. Likewise, the presence o Q-waves is less predictive o acute cardiac events. Electrical alternans or low voltage: The ndings o electrical alternans or low voltage in an ECG or a patient with chest pain should prompt consideration o pericardial e usion or hemorrhage. ECG abnormalities are common a ter stroke. Cerebral T waves (deep, symmetric T-wave inversions) can be seen with subarachnoid hemorrhage. ST-segment deviations may occur in stroke patients as well, sometimes making di erentiation between stroke and myocardial in arction challenging in di cultto-assess patients. LABORATORY TESTING Patients admitted to the hospital with chest pain or who develop chest pain while hospitalized should have basic laboratory tests per ormed, including a metabolic panel and complete blood count. Additional laboratory tests may be sent based upon clinical suspicion. Cardiac biomarkers are essential in the evaluation o patients suspected o having cardiac ischemia. Patients with possible intra-abdominal pathology should have liver enzymes and a lipase ordered as well as appropriate imaging. D-dimer testing may be appropriate in patients who present to the emergency department, but should not delay diagnostic imaging and treatment. D-dimer may not use ul in hospitalized patients when PE is a consideration due to elevation in many disorders in addition to PE and will not exclude PE in patients with a high pretest probability o PE. See Chapter 253 (Diagnosis and Treatment o Venous Thromboembolism). Cardiac biomarkers: A current de nition o myocardial in arction involves typical rise and/or all o cardiac biomarkers, along with ischemic symptoms, ischemic ECG ndings (ST-segment deviation, Q waves), and/or coronary artery intervention. Creatine kinase (CK) and the CK-MB iso orm (unique to the myocardium) have similar temporal patterns in cases o myocardial injury, rising within 4 to 8 hours and peaking between 12 and 24 hours (slightly earlier or CK-MB). CK-MB is cleared within 36 to 48 hours, and CK is cleared within 3 to 4 days. Troponin levels rise within 6 hours, peak a ter 12 hours, and are cleared a ter 7 to 14 days. Current cardiac troponin assays exhibit superior sensitivity and speci city when compared with CK and CK-MB or the diagnosis o myocardial in arction. The cardiac troponin assays are becoming the test o choice or many providers, replacing CK and CK-MB testing completely in these settings. Elevations in troponin identi y patients who would bene t rom aggressive treatment such as antithrombotic, antiplatelet, and coronary intervention. Hospitalists need to be aware o the re erence range or the speci c assay in use at their institution. The “normal range” o cardiac troponin is a troublesome concept, as any detectable troponin level has been shown to have prognostic signi cance and may be a marker o chronic as well as acute disease. Troponins may be elevated in patients with renal ailure who do not have evidence o myocardial damage. This is likely due to decreased clearance as well as increased incidence o comorbid pathology (including pathology seen at the cellular level). These patients also have a high rate o coronary disease. There ore, an appropriate serial rise in troponin is more help ul than a single

Chronic diseases

Iatrogenic disease

Myocardial injury Miscellaneous

ARDS, acute respiratory distress syndrome; CVA, cerebrovascular accident; ERCP, endoscopic retrograde cholangiopancreatogram; ESRD, end-stage renal disease; GI, gastrointestinal; HBP, high blood pressure; PE, pulmonary embolism; TTP, thrombotic thrombocytopenic purpura. Data rom Kelley WE, Januzzi JL, Christenson RH. Increases in cardiac troponin in conditions other than ACS and HF. Clin Chem. 2009;55(12):2098.

elevated, stable value or the diagnosis o myocardial in arction in these patients. Other conditions associated with increased troponin values include massive pulmonary embolism, myocarditis, cardiopulmonary resuscitation, cardioversion, heart ailure, stroke, stress cardiomyopathy, and demand ischemia (Table 79-4). NEW APPROACH TO PATIENTS PRESENTING TO EMERGENCY DEPARTMENTS WITH CHEST PAIN Based on currently available technology, evidence, and resources, hospitals and emergency departments are now ollowing a new approach based on clinical pathways. This typically involves the ollowing steps: 1. 2. 3. 4. 5.

Focused patient history and exam (see Table 79-3). Strati cation or risk o ACS Use o observation unit or extended acute care unit Appropriate testing based on initial risk strati cation Patient disposition and ollow-up based on test results

RISK STRATIFICATION OF SUSPECTED CARDIAC CHEST PAIN PATIENTS Recently, there have been several studies that ocus on strati cation o patients presenting to the emergency rooms with undi erentiated chest pain or risk o ACS. Several scores and algorithms

C H A P T E R 7 9 C h e s t P

Acute PE, ARDS Pericarditis, endocarditis, myocarditis Rhabdomyolysis Sepsis, viral disease Neuro ibromatosis, Duchenne muscular dystrophy, Klippel-Feil syndrome Carbon monoxide, hydrogen sul ide, colchicine, evenomations (snake, jelly ish, spider, centipede, scorpion) ESRD, cardiac in iltrative disorders (amyloidosis, sarcoidosis, hemochromatosis, scleroderma), HBP, diabetes, hypothyroidism Invasive procedures (heart transplant, congenital de ect repair, radio requency ablation, lung resection, ERCP), noninvasive procedures (cardioversion, lithotripsy), pharmacologic (chemotherapy) Blunt chest trauma, endurance athletes Kawasaki disease, stress cardiomyopathy, TTP, birth complications in in ants, GI bleeding

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TABLE 79-4 Differential Diagnosis of Elevated Troponin in the Absence of Acute Myocardial Infarction or Congestive Heart Failure

have been proposed. Some o these studies have used scores like TIMI (Thrombolysis in Myocardial In arction) or GRACE (Global Registry o Acute Coronary Events) and more recently developed HEART score (history, ECG, age, risk actors, and troponin). These have also been prospectively studied and they all compare well and overall provide excellent prediction o 30-day MACE (major adverse cardiac events). The TIMI score or NSTEMI continues to be an important tool due to its simplicity and also its use ulness in determining the patients disposition rom the ED as outlined below. The TIMI risk score consists o the ollowing elements: (1) age (>65 years), (2) three or more CAD risk actors (hypertension, current smoking, diabetes mellitus, hyperlipidemia, or strong amily history o early CAD), (3) known previous CAD (coronary stenosis > 50%), (4) severe angina (>2 episodes in last 24 hours), (5) aspirin use in last 7 days, (6) ECG deviation >0.5 mm, and (7) troponin elevation. Each element that is present yields one point to the risk score with a maximum score o seven. In one use ul algorithm, all the above elements except the troponin are used in the initial screening. (In other words, a modi ed TIMI or mTIMI score is used.) Then the troponin result is used to determine which type o hospital unit is best suited or the ED patient, which makes it consistent with using the whole TIMI score. See Chapter 128 (Acute Coronary Syndromes) (Figure 79-1). USE OF OBSERVATION OR EXTENDED CARE ACUTE UNITS Hospitalists are increasingly asked to manage the workup o chest pain patients who are at low, but not negligible, risk or coronary disease. The admission status o these patients will vary by institution. Chest pain “observation units” are becoming more popular and may be sta ed by emergency physicians, hospitalists, cardiologists, or nonphysician providers. The general goal o these units is to expedite the workup o patients at low-to-intermediate risk or an acute coronary syndrome. The patients are placed on predetermined clinical pathways based on initial risk strati cation. Patients that are identi ed as intermediate or high risk undergo additional testing and/ or evaluation which may include noninvasive testing like exercise ECG, myocardial per usion imaging (MPI), stress echocardiogram, or multislice CT coronary angiography. Choosing which type o testing to use will depend on the characteristics o the patient, resources available, and the policies o the institution, as well as the in ormation desired. Exercise testing with echocardiography or radionuclide myocardial per usion imaging will allow localization o abnormalities. Patients who are unable to exercise can undergo pharmacologic stress testing with dipyridamole, adenosine, or dobutamine. Dobutamine echocardiography, however, should be avoided in patients who may be su ering rom active or unstable ischemia. There is now widespread availability o multislice CT (64 slice or higher) coronary angiography in many centers with good expertise at both generating high-quality images and their interpretation. This technique adds to our diagnostic testing kit and is best used or intermediate-risk patients with no known previous CAD as outlined in our algorithm (Figure 79-2). Several recent studies have shown its use ulness given its excellent negative predictive value (99%), reduced diagnostic time, and overall cost. Coronary artery calcium (CAC) scoring is another marker o CAD. It is used as an estimate o coronary plaque burden and high CAC scores are associated with increased risk o coronary events. Additionally, in ED patients with undi erentiated chest pain a CAC o 0 is associated with a negative predictive value o almost 100% or up to 4 years o ollow-up. While CAC score is available as an independent test, it is typically included as an option in current protocols o multislice CT coronary angiography which has the

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P a tie nt with s us pe cte d ca rdia c che s t pa in

Che ck vita ls , phys ica l e xa m; AS A a nd NTG if indica te d. P e rform ECG. Orde r troponin a nd che ck x-ra y

Re vie w ECG for S TEMI/ne w LBBB

If S TEMI/ne w LBBB. Activa te ca th la b/ca ll ca rdiology. Follow ACC/AHA guide line s . If uns ta ble vita ls /high-like lihood ECG/ongoing che s t pa in with high s us picion of ACS , a dmit to ca rdia c ICU

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1. Age >65 y 2. ≥3 ris k fa ctors — dia be te s ,s moking, HTN, hype rchole s te role mia , fa mily his tory 3. P rior corona ry e ve nt/s te nos is (hx of MI, CAD, P CI) 4. ≥2 a ngina l e ve nts in prior 24 h 5. S T de via tion > 0.5 mm 6. As pirin us e in la s t 7 d

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If No S TEMI, s ta ble vita ls , minima l or no CP , low or inte rme dia te like lihood ECG, Ne ga tive CXR. Ca lcula te mTIMI s core (0–6)

mTIMI = 1, low ris k

mTIMI = 2–4, inte rme dia te ris k

mTIMI = 5–6, high ris k

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CP > 20 min /Age >40 y/>2 ris k fa ctors

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Che ck troponin re s ult

Che ck troponin re s ult

No

Look for nonca rdia c e tiology. Cons ide r D/C from ED if troponin ne ga tive with outpa tie nt follow-up OR tra ns fe r to OBS unit

Norma l

Borde rline

Abnorma l

Norma l or borde rline e le va tion a nd CP fre e

No OBS ERVATION UNIT Continuous ca rdia c monitoring; rule out MI with s e ria l troponin che cks , s e ria l ECGs , pe riodic re -e va lua tion a nd te s ting a s a ppropria te

Admit to Ca rdia c Pro g re s s ive Care Unit. Follow ACC/AHA guide line s /ca rdiology cons ulta tion

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Admit to Cardiac ICU. Follow ACC/AHA guide line s

Figure 79 1 Algorithm for chest pain triage. (ACC, American College of Cardiology; AHA, American Heart Association; ASA, aspirin; D/C, discharge.)

added advantage o direct visualization o the artery and coronary plaques. Hospitalists should amiliarize themselves with the availability, advantages, limitations, risks, and contraindications o the various modalities o stress testing and imaging. For example, stress echocardiography has the advantage o no radiation exposure but may be o limited use in case o obesity or pre-existing LBBB. Cardiac CT angiography has the advantages o not needing a ull “rule out” by biomarkers prior to testing but is limited by ability o the patient to 552

hold their breath; in addition the concerns o radiation exposure and the impact on renal unction especially i the patient has known kidney disease must be considered. A patient who is able to exercise should pre erentially per orm exercise stress testing. Patient selection via risk strati cation is crucial. Applying these tests indiscriminately will adversely a ect the positive predictive value and may lead to unnecessary downstream risk o additional testing and invasive coronary angiography. The indications or noninvasive testing or ACS in women are similar to men. However, the predictive

Known prior CAD

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No

(Obe s e /LBBB/LV dys function) a nd a ge >35 (me n) or >40 (wome n) Ye s

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Ca rdia c CTA**

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Obs tructive (pla que > 70%) Ye s

D/C with follow up for ris k fa ctor inte rve ntion

Comple te rule out, s e ria l ECGs . Cons ide r a dditiona l s tre s s te s ting for pla que 50%-69% or Ca rdiology cons ulta tion

Cons ide r low dos e a s pirin a nd s ta tin

S tre s s Echo*** (pha rma cologic if una ble to a chie ve ta rge t HR)

Admit a nd Ca rdiology cons ulta tion

No

Cons ide r low dos e a s pirin a nd s ta tin

D/C with follow up for ris k fa ctor inte rve ntion

Figure 79 2 Suggested work-up protocol for low-to-intermediate risk patients. (CTA, CTangiography; D/C, discharge.) **Relative contraindications include intolerance to betablocker, creatinine clearance 6 days. Neostigmine 2.0 mg administered intravenously can be used to decompress patients with acute intestinal pseudoobstruction. The response usually occurs rapidly a ter intravenous administration. The dose may be sa ely repeated i colonic dilatation recurs. In a small placebocontrolled randomized study, 91% o those receiving neostigmine experienced a reduction in abdominal distention. However, patients must undergo cardiac monitoring while receiving IV neostigmine, and atropine must be on hand in the event that severe bradycardia is induced. Contraindications to neostigmine use include ischemia, active bronchospasm, serum creatinine >3 mg/dL, cardiac arrhythmias, pregnancy, or bowel obstruction. Alternatively, colonic decompression can be achieved endoscopically, recognizing the risk o per oration as a result o the procedure. A bowel prep should not be administered prior to this procedure. I there are concerns about recurrence, a colonic decompression tube can be le t in place temporarily. This is

C H A P T E R 8 0 C o n s t i p a

The management o acute constipation in the hospitalized patient has two arms: relieving the current discom ort associated with the constipation and preventing the situation rom arising again. The treatment o acute constipation should be dictated by these verities o the patient’s symptoms and the cause or the constipation. For example, a patient who typically had daily bowel movements but while hospitalized has had no bowel movement or several days and complains o abdominal discom ort, bloating, or distention would probably achieve the most rapid relie by taking a stimulant laxative until a bowel movement is achieved. In patients with only mild symptoms o constipation, an osmotic laxative may achieve satis actory results. Enemas may be help ul or eliminating stool rom the le t side o the colon, particularly i the patient complains o a sense o rectal ullness. An abdominal at plate can sometimes be help ul in determining the location and extent o ecal retention. In those patients who are severely constipated, right colonic stimulation may be required, and an oral stimulant laxative is suggested. Alternatively, oral lavage using large-volume PEG 3350 solutions (as used or colonoscopy preparation) can be very e ective, provided the patient is not experiencing nausea or vomiting. Reducing the amount o opioids and correcting electrolyte disturbances are paramount to the treatment and prevention o constipation. In patients with symptoms o severe constipation, stool so teners are likely to be ine ective and add little to a preventative laxative regimen. Lactulose should also be avoided in this situation, since colonic ermentation o lactulose produces gas and increases distention and abdominal pain. Rare instances o colonic per oration have been reported when lactulose has been administered in this scenario. However, lactulose may be used later to prevent recurrent constipation.

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pre erred to a rectal tube, which succeeds mostly in decompressing the le t colon.

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PREVENTING RECURRENT CONSTIPATION IN THE HOSPITALIZED PATIENT Once a satis actory bowel movement has occurred, the patient should be placed on a laxative regimen to prevent constipation rom occurring again. It is help ul to immediately start the patient on an osmotic laxative, such as lactulose or polyethylene glycol 3350, on a daily basis. Addition o a stimulant laxative may be required intermittently or daily, particularly in those individuals at high risk or recurrent constipation. This would include those who are immobile, have neurologic disease, or use opioids. CHRONIC CONSTIPATION Many patients who complain o constipation during their hospitalization have a history o chronic constipation prior to being hospitalized. It is important to recognize that the chronic constipation can be dif cult to de ne due to di ering patient and physician perceptions. Patients with chronic constipation o ten present with a variety o symptoms including hard or lumpy stools, in requent stools, excessive straining, eeling o incomplete evacuation, and rectal ullness or discom ort. The Rome III classi cation accounts or this heterogeneity o symptoms by basing its criteria on symptoms. Using Rome III criteria, a diagnosis o unctional constipation is made when two or more o the symptoms in Table 80-3 are ullled, when loose stools are rarely present without laxative use, and when the criteria or irritable bowel syndrome with constipation (IBS-C) subtype in Table 80-4 are not met. In addition, symptoms must have started ≥6 months ago and must have been present or the last 3 months. 559

TABLE 80-3 Rome III Criteria for Functional Constipation*

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1. Must include two or more o the ollowing: a. Straining during at least 25% o de ecations b. Lumpy or hard stools in at least 25% o de ecations c. Sensation o incomplete evacuation or at least 25% o de ecations d. Sensation o anorectal obstruction/blockage or at least 25% o de ecations e. Manual maneuvers to acilitate at least 25% o de ecations (eg, digital evacuation, support o the pelvic loor) . Fewer than three de ecations per week 2. Loose stools are rarely present without the use o laxatives 3. There are insu icient criteria or IBS

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Constipation can be classi ed into three pathophysiologic subtypes: normal-transit, slow-transit, and pelvic outlet dys unction. The three subtypes can overlap. Normal-transit constipation, the most common subtype, is characterized by normal colonic transit time and normal de ecatory unction. A subset o these individuals has reduced colonic tone or compliance. Slow-transit constipation is characterized by delayed transit o stool through the colon due to a myopathy or neuropathy. Slowed colonic transit arises rom diminished motor activity, such as reduced high-amplitude contractions. This type o constipation is moderately predicted by stool orm (scybalous or hard lumpy balls o stool). In contrast to slow-transit constipation, pelvic f oor dys unction, the most common subtype among women, is characterized by dif culty or inability to evacuate stool rom the anorectum. Pelvic oor dys unction can be caused by ailure o the internal anal sphincter or pelvic oor muscles to relax or paradoxical contraction o the external anal sphincter or puborectalis muscle while straining during de ecation. Pelvic oor dys unction is also re erred to as de ecatory disorder, anismus, pelvic- oor dyssynergia, paradoxical pelvic- oor contraction, obstructed constipation, unctional rectosigmoid obstruction, spastic pelvic- oor syndrome, and unctional ecal retention in childhood.

to pursuing a diagnosis o unctional constipation. Symptoms alone cannot distinguish between the subtypes o unctional constipation. Certain historical clues, however, should generate a high index o suspicion or pelvic outlet dys unction as a cause o constipation, including a sense o obstruction in the anal region, and manual maneuvers to acilitate stool evacuation, including unusual postures on the toilet, support o the perineum, digital manipulation o the rectum, and posterior vaginal pressure. While a thorough examination o the abdomen, perineum, and anorectum should be per ormed, the physical exam should pay particular attention to pelvic oor motion. The examiner should inspect or perineal abnormalities while the patient bears down, including pulling orward o the anus. While per orming the digital rectal exam, the examiner should assess sphincter tone by having the patient bear down to elicit perineal descent and relaxation o the sphincter. Abnormal ndings on palpation include high resting anal sphincter tone, descent o the perineum 3.5 cm while straining, posterior rectal wall tenderness, a palpable mucosal prolapse, or de ect in the anterior rectum. Physiologic testing or unctional constipation should be per ormed only a ter excluding secondary causes o constipation in cases re ractory to a high- ber diet and laxatives. Colonic transit studies with radiopaque markers (Sitzmarks) or scintigraphy are the initial tests o choice, allowing di erentiation between normal transit, slow transit, and pelvic outlet obstruction. The patient ingests a capsule containing radiopaque markers and an abdominal at plate is obtained 120 hours later. No markers will be retained in those with normal transit. However, markers retained throughout the colon are indicative o slow transit. Accumulation o markers in the le t colon is suggestive o pelvic outlet obstruction, but could also be compounded by slow transit. I the history and physical exam are suggestive o pelvic oor dys unction, anorectal manometry, balloon expulsion testing, and de ecography are use ul tests. Anorectal manometry assesses rectal sensation and compliance, sphincter pressures, and anorectal re exes. The test may suggest Hirschsprung disease. The balloon expulsion test can identi y but cannot exclude dyssynergic de ecation. As an adjunct to other testing, MRI or video de ecography can be used to con rm or exclude pelvic oor dys unction, and can identi y a clinically signi cant rectocele, rectal intussusception, and rectal prolapse. Finally, electromyography o the anal sphincter muscles can evaluate or dys unction o the striated pelvic oor muscles.

■ EVALUATION The initial evaluation o a patient presenting with chronic constipation should consist o a care ul history, physical examination, laboratory testing, and imaging to exclude secondary causes, prior

■ MANAGING CHRONIC CONSTIPATION PRACTICE POINT

• TABLE 80-4 Rome III Diagnostic Criteria for Irritable Bowel Syndrome with Constipation (IBS-C)* Recurrent abdominal pain or discom ort ? at least 3 d per month in the last 3 mo associated with two or more o the ollowing: 1. Improvement with de ecation 2. Onset associated with a change in requency o stool 3. Onset associated with a change in the orm (appearance) o stool—hard or lumpy stools§ ≥ 25% and loose (mushy) or watery stools¶ < 25% o bowel movements** Criteria ul illed or the last 3 mo with symptom onset at least 6 mo prior to diagnosis. ? Discom ort means an uncom ortable sensation not described as pain. § Bristol Stool Form Scale 1–2 (separate hard lumps like nuts [di icult to pass] or sausage-shaped but lumpy). ¶ Bristol Stool Form Scale 6–7 ( lu y pieces with ragged edges, a mushy stool or watery, no solid pieces, entirely liquid). **In the absence o use o antidiarrheals or laxatives. *

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No currently available stimulant laxatives have been associated with an increased risk or neoplasia. The evidence that chronic stimulant laxative use damages neurons and causes cathartic colon is very limited and remains controversial.

Understanding how each laxative type works is essential or proper management o acute and chronic constipation (Table 80-5). For those individuals with mild, intermittent constipation, use o an occasional stool so tener or magnesium-based osmotic laxative can be e ective. Nearly all patients can bene t somewhat rom increasing daily ber consumption to at least 30 g per day. Daily ber, be it insoluble or soluble, can be consumed in the diet or by use o one o numerous ber supplements available over the counter. Patients should be encouraged to use the equivalent o 5 to 10 g o ber daily, be it in the orm o a supplement or oods, such as a high- ber cereal that gives 10 to 13 g per cup. When using ber to manage constipation, patients must be in ormed be ore they become discouraged that they may not observe a change in their stool

Detergents/stool so teners Docusate sodium Liquid para in Prokinetic agents Colchicines Misoprostol Chloride channel activator Lubiprostone Opioid antagonists Methylnaltrexone Alvimopan Enemas and suppositories Sodium lauryl sulphoacetate, osmotic agents, glycerol Saline and water enema Hypertonic sodium phosphate enemas Glycerin suppositories, bisacodyl suppositories or enema, oxyphenisatin

consistency or 7 to 14 days a ter initiating daily ber supplementation. In addition, they may experience increased gassiness during this 2-week period as a result o increased bacterial ermentation. Patients with irritable bowel syndrome may be exquisitely sensitive to the gas produced by increased ber intake and may be intolerant o it. In patients who report passage o hard, scybalous, stool with either normalor slow-transit constipation, i ber ails to alleviate the hard stool, addition o a daily osmotic laxative, such as lactulose or PEG 3350, is usually e ective. Because osmotic laxatives are not the same as stimulant laxatives, patients must be told to assess the ull impact o this regimen a ter 7 to 14 days have passed. A ter that, the dose and timing o the laxative can be adjusted to better suit the li estyle and expectations o the patient. Lubiprostone, a calcium channel stimulator, draws water into the colon and can be used in patients with mild-to-moderate constipation. The advantage o lubiprostone is that it is available in pill orm, but does cause nausea in a third o users, and there ore should be taken with ood. In a clinical trial involving individuals with chronic constipation, the majority o individuals had a bowel movement within 24 to 48 hours o taking the medication. Lubiprostone has also been approved by the FDA or the treatment o IBS-constipation, but at a dose o 8 mcg bid as opposed to 24 mcg bid approved or unctional constipation. Linaclotide is also a secretory agent like lubiprostone, but linaclotide works through a di erent mechanism as a guanylate cyclase C agonist. It is taken orally, 30 minutes prior to the rst meal. A th o users experience diarrhea. Patients who respond to linaclotide should expect improvement in bowel movement requency and/or abdominal pain within 1 week. Linaclotide is FDA approved or the

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Stimulant laxatives Anthraquinones: senna, aloe, cascara, rangula Polyphenolic (diphenylmethane) compounds: bisacodyl, sodium picosul ate

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TABLE 80-5 Pharmacologic Agents Used to Treat Constipation

treatment o chronic idiopathic constipation at a dose o 145 mcg and is also approved or IBS-constipation at 290 mcg. Prucalopride, a 5-hydroxytryptamine-4 (5-HT4) receptor agonist, stimulates intestinal motility, and is approved in Europe or the treatment o chronic constipation in women, but has been shown to increase the number o weekly bowel movements and improve symptoms in men. In patients with pelvic oor dys unction, use o a suppository can be help ul i rectal stimulation is required to initiate the bowel movement. These patients requently bene t rom using a stimulant laxative, such as a sennasoide, bisacodyl, or sodium picosul ate, every day or every other day. Occasional enema use can also help address the le t-sided ullness and stimulate de ecation. Patients with pelvic oor dys unction may also report hard stool, so a regimen using both an osmotic and stimulant laxative is sometimes required. Patients requently express concern about long-term stimulant laxative use. They ear chronic use causes “dependency” or a “lazy colon.” Many health care providers share this concern because o early reports o a possible relationship between chronic stimulant laxative use and cathartic colon. However, the evidence that chronic stimulant laxative use damages neurons and causes cathartic colon is very limited and remains controversial. While it is true that chronic use o an anthraquinone may cause the di use colonic pigmentation known as melanosis coli, this is o no clinical signi cance. An additional concern was that use o stimulant laxatives could increase cancer risk. Most phenolphthalein-containing laxatives were withdrawn rom the market when they were shown to increase ovarian, adrenal, renal, and hematopoietic neoplasms in rodents. No other stimulant laxatives have been associated with an increased risk or neoplasia. Special attention is given here to managing constipation in the patient who chronically uses opioids or pain management. Eightyone percent o chronic users will report constipation. Opioids, which activate µ-receptors widely distributed among the neurons o the myenteric and submucosal plexus and immune cells in the lamina propria, inhibit excitatory neural pathways thereby delaying intestinal transit. They also inhibit water and electrolyte secretion into the gut lumen. Constipation is this patient population may be additionally managed by attempting to reduce the amount o opioids used. Another possibility is to consider substituting a central µ-opioid agonist and norepinephrine reuptake inhibitor, such as tapentadol, which appears to be less constipating compared to oxycodone. Finally, peripheral µ-receptor antagonists naloxone and methylnaltrexone can be used to treat opioid-induced constipation. Prolonged-release naloxone when given in combination with prolonged-release oxycodone does not reverse the analgesia but improves bowel unction. Methylnaltrexone, which is FDA approved or the treatment o opioid-induced constipation in patients taking opioids or noncancer pain, is administered as a subcutaneous injection, and 50% to 60% will experience a bowel movement within 4 hours a ter injection. The injection may be repeated every other day. Another peripheral µ-receptor antagonist, alvimopan, is currently FDA approved only or the use in postoperative ileus. TIMING OF CONSULTATION WITH A GASTROENTEROLOGIST OR A SURGEON A GI and/or surgical consultation should be obtained or any constipated patient who has severe pain, pain out o proportion to exam, or who has signs suggesting development o a serious complication, such as ischemia, per oration, or obstruction. A consultant may be particularly help ul in the management o suspected colonic obstruction. Treatment o sigmoid volvulus includes placement o a temporary rectal tube or endoscopic reduction as long as there are no clinical, radiological, or laboratory signs o ischemia or per oration. Barium enema may also be per ormed,

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but carries a higher risk o per oration than endoscopic decompression. Sigmoid volvulus is very amenable to initial endoscopic reduction, but recurrence rate may be as high as 70% so elective resection a ter decompression is recommended. Any sign o ischemia, such as bloody stool, during endoscopic reduction is an indication or urgent surgery. Endoscopic reduction o cecal volvulus is success ul in only 30% o cases, so surgery is generally recommended as rstline treatment unless the patient is a poor surgical candidate. Benign or malignant colonic strictures can be diagnosed by colonoscopy and biopsy. Benign strictures can be dilated endoscopically using balloon dilators or colonic stents. Surgery may be necessary to resect benign or malignant colonic strictures.

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A major contributing actor to constipation emerging as an active issue in the hospitalized patient is the ailure to obtain an accurate history o chronic constipation and not continuing the patient’s home laxative regimen. In act, it is very common or admitting orders on some services to ignore the patient’s home laxatives and re exively include an order or stool so teners. Stool so teners are largely ine ective in patients who take opioids, have undergone surgery causing them to be bedridden, or have a history o chronic constipation. In the acutely hospitalized older patient, the use o laxatives at home was a good predictor or constipation while in the hospital. There is also the mistaken impression that patients who are not eating will not have any bowel movements at all. Identi ying the risks or constipation, as well as a prior history o constipation, is essential or preventing constipation in the hospitalized patient. In those at high risk, starting a daily osmotic laxative can be highly e ective, recognizing that their e ectiveness may

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not be immediately apparent. In selecting an osmotic laxative, it is important to be aware that requent administration o magnesiumbased compounds raises serum magnesium levels in patients with chronic renal insuf ciency. A daily stimulant laxative may be help ul in those at highest risk or in whom the history suggests pelvic oor dys unction. CONCLUSION Constipation is a common problem in the hospitalized patient. New constipation may be precipitated by many actors associated with hospitalization. Recognizing the risks or constipation is the mainstay o managing and preventing constipation. The major risks are a prior history o chronic constipation, use o constipating medications, particularly opioids, and lack o physical activity due to medical illness or surgical recovery. Selecting the proper laxative or management or prevention o constipation requires amiliarity with the di erent types o laxatives and educating patients about these di erences to address their expectations about their ef cacy. Finally, it is also essential or the hospitalist to recognize when constipation is actually a mani estation o an acute, possibly emergent event that requires immediate management by consultants.

SUGGESTED READINGS American Gastroenterological Association, Bharucha AE, Dorn SD, Lembo A, Pressman A. American Gastroenterological Association medical position statement on constipation. Gastroenterology. 2013;144(1):211-217. Bharucha AE, Pemberton JH, Locke GR 3rd. American Gastroenterological Association technical review on constipation. Gastroenterology. 2013;144(1):218-38. Lal SK, Morgenstern R, Vinjirayer EP, Matin A. Sigmoid volvulus an update. Gastrointest Endosc Clin N Am. 2006;16:175-187. Leppert W. Emerging therapies or patients with symptoms o opioid-induced bowel dys unction. Drug Des Devel Ther. 2015; 9:2215-2231. Rao SS. Constipation: evaluation and treatment o colonic and anorectal motility disorders. Gastroenterol Clin North Am. 2007;36: 687-711.

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CHAP TER

Delirium Karin J. Neu eld, MD, MPH Laura K. Max, BA Makeida B. Koyi, MD Dale M. Needham, MD, PhD

Key Clinical Questions 1

What is the prevalence o delirium in hospitalized patients?

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What are the most common causes o delirium?

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Why is it important to detect delirium?

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How is delirium diagnosed?

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How can delirium be prevented and treated?

INTRODUCTION Delirium is common in hospitalized patients. The prevalence o delirium may be as high as 80% in mechanically ventilated patients in the intensive care unit (ICU), 50% in geriatric postoperative patients, and 10% to 40% in general medical patients. Patients who develop delirium requently have multiple risk actors. These include nonmodi able actors, such as increased age, pre-existing cognitive impairment, and a history o prior stroke or brain injury. Important modi able risk actors include (1) exposure to deliriogenic medications, (2) in ection, (3) metabolic derangement, (4) organ ailure, (5) dehydration, (6) malnutrition, (7) surgery, (8) immobility, (9) use o physical restraints, (10) sensory impairment, (11) sleep deprivation, (12) pain, and (13) drug withdrawal or intoxication.

PRACTICE POINT Delirium as a red f ag • Delirium is a nonspeci c warning sign, like ever or hypotension, indicating that something serious may be wrong and requires urther investigation. Thirty-nine percent o inpatients with delirium die within one year. Do not ignore this red f ag. Delirium is associated with increased mortality, morbidity, and length o stay. Estimates o annual US health care costs attributed to delirium range rom $40 billion to $150 billion. Delirious patients require extra care ollowing discharge rom acute inpatient units and are at increased risk o being discharged to a skilled nursing acility rather than directly home. Patients o ten su er rom rightening memories o delirious episodes while hospitalized. Such experiences may result in appreciable anxiety and preoccupation long a ter delirium has cleared, impacting the patient’s quality o li e or months to years. Family members are o ten distressed by the changed demeanor and behavior o their loved one, making care and support more challenging. PATHOPHYSIOLOGY The central eature o delirium is an acute disturbance o consciousness accompanied by altered cognition or perception. Disruptions in brain unction occur in the brainstem, thalamus, pre rontal cortex, usi orm cortex, and parietal lobes. This widespread cortical dys unction is typically associated with di use and symmetric slowing o electrical activity on electroencephalography (EEG), although ast electrical activity occurs in some cases, especially in alcohol or sedative withdrawal.

PRACTICE POINT

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The diagnosis o delirium requires diminished attention and awareness, evolving over a short period o time (hours to days), waxing and waning in severity, and associated with other disturbances in cognition, such as memory de cits and disorientation. Delirium cannot be wholly explained by a pre-existing neurologic disorder. History, physical examination, laboratory testing, and imaging should reveal one or more inciting actors, such as electrolyte disturbances, in ections, adverse e ects o medications, or drug and alcohol withdrawal syndromes. 563

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Dire c t Is c he mic Damag e

Cyto kine Imbalanc e

S ys te mic Infla mma tion

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Ac ute S tre s s Re s p ons e Gluc oc ortic oid s Cus hing ’s S ynd rome

Figure 81 1 Pathophysiology o delirium.

Figure 81-1 depicts numerous potential pathways to delirium and underscores its complex pathogenesis. Neurotransmitter imbalances, especially cholinergic de ciency and dopaminergic excess, may play a key role in the development o delirium. This hypothesis is supported by the observation that anticholinergic and dopaminergic drugs requently precipitate delirium, whereas antidopaminergic drugs, such as antipsychotics, have been used to treat the symptoms o agitation associated with delirium. Other neurotransmitters, such as glutamate, GABA, serotonin, norepinephrine, and histamine, have also been implicated in the pathogenesis o delirium. For example, norepinephrine and glutamate hyperactivity and GABA hypoactivity are associated with delirium tremens, while GABA hyperactivity is associated with hepatic encephalopathy. Proin ammatory cytokines have a direct neurotoxic e ect on the brain and a ect the synthesis and release o neurotransmitters, thereby contributing to delirium. Finally, elevated cortisol levels and ischemic brain damage rom hypoper usion or hypoxia also have been linked to delirium. DIAGNOSIS OF DELIRIUM The diagnosis o delirium is based on a relatively abrupt alteration in the level o consciousness, which o ten waxes and wanes over the course o a day, with associated inattention and changes in cognition or perception. Due to inattention, patients may ask the same question repeatedly or perseverate on an issue. Cognitive de cits may a ect short-term and intermediate recall, word nding, orientation, and the ability to learn new in ormation. Perceptual disturbances, such as illusions or hallucinations, are also common. Illusions are misinterpretations o stimuli (eg, mistaking an intravenous line or a snake), while hallucinations are perceptions without stimuli. Hallucinations are most requently visual (eg, seeing bugs crawling on the walls), but can be auditory (eg, hearing voices), or tactile (eg, eeling bugs crawling on the skin). These disturbances arise as physiologic 564

consequences o medical illness or rom substance intoxication or withdrawal, rather than rom an underlying psychiatric condition. Other common eatures o delirium are not necessary or diagnosis but are noteworthy because they o ten mimic mental illness. Patients may develop xed, alse, idiosyncratic belie s (delusions), o ten persecutory in nature. For example, delirious patients commonly believe that their nurses or doctors intend to harm them. Other requent ndings include speech that is dif cult to ollow or that requently wanders o topic (disorganized speech). Patients may also experience signi cant and rapid shi ts in emotional tone (a ective lability), with bouts o tear ulness, anxiety, or increased irritability. Sleep-wake cycle disruption, with increased napping during the day and dif culty with sustained sleep at night, is present in most cases o delirium. Subtypes o delirium are distinguished by the predominant level o psychomotor activity. The hypoactive subtype is characterized by decreased motor activity and increased somnolence. Patients appear quietly indi erent to their surroundings and have great dif culty arousing and sustaining attention. Treating physicians may misattribute this presentation to a depressive disorder. The hyperactive subtype is associated with increased motor activity and agitation. Patients are restless, talkative, and aroused. They may pull at intravenous lines and indwelling catheters or even strike out against caregivers. Although they appear ully alert, these patients have trouble sustaining attention. The mixed subtype includes eatures o both increased and decreased psychomotor activity. While hyperactive behavior is easy or nurses and doctors to identi y, hypoactive delirium is o ten overlooked because these patients are not demanding, and their cognitive limitations must be elicited through direct cognitive examination. To avoid missing hypoactive delirium, physicians must maintain a high index o suspicion and should expect all patients to be easily arousable and able to per orm basic cognitive tasks at their preadmission baseline.

DIFFERENTIAL DIAGNOSIS Physicians requently misattribute signs and symptoms o delirium to psychiatric illness. For example, distinguishing delirium rom dementia can be challenging. Both diagnoses are associated with cognitive impairment. However, dementia without superimposed delirium does not result in uctuating levels o consciousness. The patient’s recent baseline physical and mental status, along with timing o onset, pattern o symptom uctuation, and duration o symptoms will help to distinguish these two syndromes and should be care ully elicited rom collateral in ormants such as the amily and bedside nurse. Delirium has its onset over hours to days, while dementia involves a protracted decline over months to years. Sundowning re ers to an increase in con usion and agitation during late a ternoon and evening among a subset o patients with dementia. Some authors regard this as a delirium-related phenomenon. However, little systematic research has been conducted, and multiple other etiologies have been proposed. The phenomenon has been explained as a response to atigue or to unmet physical or psychological needs, or as a consequence o underlying sleep disorders or inadequate daytime light exposure. It must be remembered that demented patients are at signi cant risk o developing delirium. Whenever there is a uctuating level o consciousness, a workup or medical causes o delirium should be initiated. Delirium, especially the hypoactive subtype, is also commonly con used with a depressive illness. Patients with either diagnosis may have signi cant psychomotor slowing, poor oral intake, and sleep disruption. They may appear withdrawn and sad, and they may even express a desire to die or end their lives. However,

C H A P T E R 8 1 D e l i r i u

depressed patients do not experience alterations in level o consciousness. They may be inattentive and have problems with shortterm recall, but they remain oriented. They also requently have a personal or amily history o depression and describe a gradual onset o symptoms, in contrast to the acute onset observed with delirium. A number o other psychiatric disorders also may be misdiagnosed in the delirious patient. Hyperactive delirium may be con used with mania, and prominent hallucinations or delusions requently raise concern or schizophrenia. Delirious patients who are anxious may be misdiagnosed with anxiety disorders. Moreover, those who are irritable (such that they re use medical care) or inattentive (such that they ail to ollow nursing instructions) may be considered “dif cult” or “noncompliant,” even when their behaviors result rom delirium and are beyond their control. In all these cases, i there is a uctuating level o consciousness or disorientation, delirium is more likely than any other psychiatric condition. The past psychiatric history and timing o symptom onset are also essential in making a diagnosis. Most psychiatric disorders present by early adulthood (although there are exceptions, such as depressive disorders). A geriatric patient suddenly seeing cats running across the hospital oor, or who is described by amily members as usually “easy-going and slow-to-anger” but is now ound to be “dif cult,” is more likely to have new-onset delirium, rather than a new-onset psychiatric disorder. Because delirium can masquerade as almost any psychiatric disorder, it is imperative that physicians avoid basing any new psychiatric diagnoses on a patient’s mental status while he or she is still delirious. Even i history obtained rom collateral in ormants suggests that there is an underlying anxiety disorder or major depressive disorder, pharmacologic treatment o these disorders should not be initiated until the patient’s delirium has cleared, since new medications may worsen the delirium, and response to a new medication cannot be properly assessed while a patient is still delirious. Physicians should also be wary o attributing psychiatric symptoms to a patient’s known chronic psychiatric illness without thoroughly evaluating whether the symptoms are consistent with that illness. Just as demented patients can become delirious, so can patients with any other psychiatric disorder.

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There are many screening and delirium diagnostic tools available to rate the presence or absence and severity o delirium. Diagnostic algorithms such as the Con usion Assessment Method, or rating tools such as the DRS-98R or Memorial Delirium Rating Scale, are generally most valid when used by a clinical expert or trained evaluator. Because the rating o diagnostic tools and algorithms is based on a care ul clinical examination that includes ormal cognitive assessment, use o these tools takes much more time than delirium screening instruments. Screening tools, designed or use by nonspecialist bedside personnel, can be per ormed in less than 2 minutes. For patients in the ICU setting, the CAM-ICU (a modi ed version o the CAM that can be administered to nonverbal, mechanically ventilated patients) has been demonstrated to be a valid and highly reliable screening tool (with pooled sensitivity and speci city o 76%-80% and 96%, respectively) that is easily administered by ICU nurses. Another validated instrument or the critical care setting is the Intensive Care Delirium Screening Checklist (ICDSC), a cumulative checklist that is completed during each nursing shi t over a 24-hour period with sensitivity and speci city o 80% and 96%, respectively. Both the CAM-ICU and the ICDSC can be downloaded rom the ollowing website: http://www.icudelirium.org. The sensitivity o these particular instruments in a noncritically ill patient population is too limited or generalized use. Other tools or widespread use in noncritically hospitalized patients include the 4AT (available at http://www.the4at.com) which has been validated in a number o inpatient populations including older individuals with dementia and neurology inpatients. Other screening tests include the 3D-CAM, which has been validated in a geriatric population. Finally, the EEG, which typically reveals di use slowing in the setting o delirium (except in delirium tremens, which is associated with ast activity), may help support a diagnosis o delirium or rule out nonconvulsive seizure activity. However, it should not be used as a primary diagnostic tool or delirium, as it is neither suf ciently sensitive nor speci c.

TREATMENT OF DELIRIUM Delirium is an important medical indicator. It may be the rst sign o a new li e-threatening medical condition, such as organ ailure, overdose, in ection, or a central nervous system (CNS) event (see Table 81-1 or a list o common causes). The most important goal in treating delirium is to discover and correct the underlying cause(s). The diagnostic workup o delirium is outlined in Figure 81-2. Clinicians should start by reviewing the history, doing a physical exam, including brie cognitive tests o mental status, and per orming basic laboratory investigations.

■ WITHDRAWAL-RELATED DELIRIUM As a rst step, determine whether alcohol, benzodiazepine, or barbiturate withdrawal is a cause o the delirium. Obtain a history rom the patient and collateral in ormants (including outpatient health care providers) to determine the duration, pattern, and quantity o alcohol intake; the extent o any prescription or illicit use o benzodiazepines or barbiturates; and whether there are any prior episodes o withdrawal symptoms. Review the street names or readily available prescription drugs in your area. For example, “pins” can re er to Klonopin (clonazepam) tablets, and “bars” can re er to 2-mg Xanax (alprazolam) tablets, which are commonly sold in illicit settings. 565

TABLE 81-1 Causes o Delirium: “DELIRIVM”

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D Drugs/poisons • Medications (see Table 81-2) • Drugs o abuse (eg, alcohol, cocaine, PCP, inhalants) • Industrial poisons (eg, organophosphates, heavy metals, organic solvents) • Animal, plant, and mushroom toxins • Withdrawal ( rom alcohol or sedatives/hypnotics) E External insults • Closed-head injury • Heat stroke • Hypothermia • Electrocution L Lesions rom cancer • Primary brain cancer • Meningeal carcinomatosis • Metastatic lesions (especially rom melanoma and lung, breast, colon, and kidney cancers) I In ections • Intracranial (bacterial/viral/ ungal encephalitis or meningitis, brain/epidural/subdural abscess, trichinosis, cerebral malaria, ungal in ections, Creutz eldt-Jakob disease, neurosyphilis; in HIV/AIDS: cytomegalovirus encephalitis, cryptococcal meningitis, progressive multi ocal leukoencephalopathy, toxoplasmosis, tubercular meningitis) • Systemic (sepsis, pneumonia, subacute bacterial endocarditis, in luenza, mononucleosis, mumps, typhoid ever, Lyme disease, Behçet disease, brucellosis, psittacosis, Rocky Mountain spotted ever, typhus; in HIV/AIDS: disseminated herpes zoster, candidiasis) R Remote e ects o cancer (paraneoplastic syndromes) • Paraneoplastic limbic encephalitis (especially with lung, breast, or testicular cancers; paraneoplastic syndromes may occur be ore there are any signs o cancer on imaging) I Ictal/interictal/postictal (seizures) V Vascular causes • Emboli rom cardiac source • Intracranial bleed or thrombosis • Hypertensive encephalopathy • Autoimmune (lupus cerebritis, sarcoid, polyarteritis nodosa, thrombotic thrombocytopenic purpura) • Circulatory collapse (shock) M Metabolic causes • Hypoxia • Hypoglycemia • Electrolyte imbalance (hyponatremia, hypernatremia, hypercalcemia, hypocalcemia, hypokalemia, hyperkalemia, hypomagnesemia, hypermagnesemia, hypophosphatemia) • Acidosis or alkalosis • Errors o metabolism (porphyria) • Vitamin de iciency (vitamin B12, thiamine, nicotinic acid) • Vitamin intoxication (vitamin A, vitamin D) • Organ ailure (kidney, liver, lungs, pancreas) • Endocrinopathies (hyperthyroidism, hypothyroidism, hyperparathyroidism, hypopituitarism, Addison disease, Cushing syndrome, insulinoma, diabetic ketoacidosis, hyperosmolar nonketotic hyperglycemia)

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I a patient is in withdrawal, physical examination will typically reveal autonomic arousal, with hypertension, ever, tachycardia, tongue and extremity tremor, pupillary dilation, sweating, and motor restlessness, or pronounced instability o vital signs. Peak autonomic withdrawal rom alcohol occurs 72 to 96 hours rom the last drink, while withdrawal rom long-acting benzodiazepines such as diazepam may take up to 1 week to peak. Delirium may then extend several weeks beyond the presence o withdrawal signs. GABAergic agents such as chlordiazepoxide, diazepam, oxazepam, or lorazepam are the treatment o choice. Symptom-triggered dosing o a short-acting agent (eg, oxazepam 15-30 mg orally or lorazepam 1-2 mg IV every 2 hours as needed or symptoms o withdrawal, such as tremor, agitation, or insomnia) is associated with better outcomes than xed titration schedules, but requires regular screening or symptoms o withdrawal by bedside sta . Another approach is to give a loading dose o a long-acting agent (eg, chlordiazepoxide 50-100 mg orally every 1-2 hours or mildto-moderate withdrawal or diazepam 5-10 mg IV as requently as every 5-10 minutes or severe withdrawal) until the patient is calm. The long hal -li e o these agents allows or a smooth sel -taper a ter discontinuation. In the event o breakthrough withdrawal signs, additional medication (eg, chlordiazepoxide 25-50 mg orally or diazepam 5-10 mg IV) can be given every 2 hours as needed. Individuals with advanced liver disease should be treated with oxazepam or lorazepam pre erentially, as these medications have shorter hal -lives and no active metabolites. I the patient cannot be closely monitored or signs o withdrawal, then these short-acting agents should be given on a xed schedule and tapered by 20% to 25% daily. Although symptom-triggered dosing has been associated with less total benzodiazepine administration and ewer days o delirium per patient than xed schedule therapy, it is ully e ective only when nurses have both the time and ability to monitor patients regularly and requently. I a patient’s delirium worsens or ails to respond to treatment with benzodiazepines, the treating physician should consider alternative etiologies o the patient’s continued delirium. For example, i a ormerly agitated patient becomes sedated and con used, clinicians should consider both overuse o benzodiazepines and hepatic encephalopathy.

■ MEDICATION-RELATED DELIRIUM Medication lists o delirious patients should always be reviewed to look or any new medication that coincided with the onset o delirium. In the setting o worsening kidney or liver unction, a previously well-tolerated medication may cause delirium due to decreased drug clearance. The addition o new medications may render an old medication newly deliriogenic by inhibiting its metabolism, or old medications may cause delirium in the setting o new neurologic insults. Review the medication list or anticholinergic and other requently implicated agents (Table 81-2) and discontinue or replace these medications. I history and physical exam reveal little or no risk o withdrawalrelated delirium, avoid using benzodiazepines (unless a patient was taking them prior to admission, in which case they should be continued at the preadmission dose). Avoid even the nonbenzodiazepine hypnotics, or “z” drugs used or sleep, such as zolpidem or zaleplon. These medications can also cause or contribute to delirium. Anxiety and agitation are common in delirious patients. Resist the urge to treat with benzodiazepines. I reassurance and redirection ail to calm a patient’s severe agitation, try antipsychotics instead (Table 81-3), particularly i agitation is due to psychotic symptoms such as delusions or hallucinations.

a s a pos s ible ca us e of de lirium (withdrawa l-re la te d guide line s )

Review me dic atio n lis t

•

•

Doe s the a ddition of a new me dica tion coincide with the cha nge in me nta l s ta te ? Dis continue /re pla ce offe nding drugs, s uch a s Be nzodia ze pine s Propofol Nonbe nzodia ze pine hypnotics Anticholine rgics Corticos te roids Opioids Antihis ta mine s

Ens ure ade quate analg e s ia

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Ens ure re gula r pa in a s s e s s me nt a nd a dminis tra tion.

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Dis continue pa tie nt–controlle d a na lge s ia device (P CA) until me nta l s ta te cle a rs.

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• • •

S e arc h fo r and tre at any ne w infe c tio ns

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Review CBC, urina lys is, a nd CXR.

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Obta in blood culture s if the pa tie nt is fe brile.

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Ge t a he a d CT a nd lumba r puncture if he a da che or nucha l rigidity a re pre s e nt.

Ens ure ade quate nutritio n, hydratio n, and re g ular bowe l move me nts Re ple te thia mine if evide nce of a lcohol us e dis orde r a nd/or ma lnutrition.

Ta pe r a nd continue a ny a ntipsychotic me dica tion.

•

Encoura ge pa tie nt to s ha re a ny expe rie nce s tha t they re ca ll of the de lirium.

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Provide cue s with the da te, pa tie nt’s loca tion, a nd na me s of ca re te a m me mbe rs.

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Encoura ge fa mily to bring in photogra phs a nd fa milia r ite ms from home, to vis it fre que ntly, a nd to s tay ove rnight.

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Ve rba lly re orie nt a nd re a s s ure pa tie nt throughout the day.

C H T E R u

Provide g las s e s and he aring aids (if a pplica ble ) Take s te ps to re duc e ag itatio n

Co ns ide r the fo llowing te s ts if initial wo rk-up prove s ne g ative :

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Obta in a 24-h s itte r or fa mily me mbe r to re dire ct a nd re a s s ure the pa tie nt.

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Turn off the TV, play s oothing mus ic, a nd s pe a k ca lmly a nd s oftly to the pa tie nt.

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Tre a t a gita tion with ne urole ptics if re dire ction a nd re a s s ura nce fa il.

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Re move urina ry ca the te rs a nd IV’s if pos s ible.

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RP R, ANA, HIV, a mmonia He avy me ta l s cre e n, urine porphyrins, pa ra ne opla s tic a ntibodies

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Enga ge in phys ica l a nd occupa tiona l the ra py.

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EEG to rule out nonconvuls ive s ta tus– e pile pticus

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Ambula te with he lp of s ta ff or fa mily.

Mo bilize the patie nt

Bra in ima ging

Improve s le e p–wake c ycle

Thia mine 500 mg IV/IM TID X1 day the n 500 mg ×5 days, the n 100 mg P O/IM/IV da ily.

•

Re o rie nt the patie nt re g ularly

S e nd urine for culture a nd s e ns itivity if urina lys is is a bnorma l.

Co ns ide r wo rs e ning o rg an failure e g, kidney, live r): che ck la bs a nd corre ct whe re pos s ible. Co ns ide r hypoxia o r hype rc arbia: Ge t blood ga s /puls e oxime try a nd CXR. If indica te d, provide s upple me nta l oxyge n or noninva s ive ve ntila tion. Co rre c t abno rmal e le c tro lyte s : Aim for Na clos e to 140; tre a t hype r-a nd hypoca lce mia ; Corre ct hypoma gne s e mia

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Targ e te d te s ting Bas ic te s ts s hould include a CBC, CMP, Ca , Mg, phos pha te, glucos e, thyroid function te s ts, B12, ECG, CXR, oxyge n s a tura tion, urine toxicology s cre e n, a nd urina lys is.

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Phys ic al exam Include a comple te ne urologic exa m. Me nta l s ta tus exa m s hould a s s e s s leve l of a le rtne s s, orie nta tion, me mory, a tte ntion a nd la ngua ge. As s e s s ca pa city for me dica l de cis ion ma king.

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Co ns ide r alc o ho l o r be nzo diaze pine withdrawal

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Ge t a his to ry—lo o k fo r evide nc e o f an ac ute c hang e in me ntal s tatus Obtain his to ry fro m info rmant: His tory s hould include a time -cours e of cha nge s in be havior a nd cognition; s ubs ta nce a bus e his tory; a nd a comple te lis t of me dica tions including “ove r-the -counte r.”

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DELIRIUM WORK-UP AND TREATMENT PATHWAY

Pa tie nt improve s

Ye s

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Re orie nt pa tie nt to day/night (Ke e p lights on a nd blinds ope n during day; ke e p room dimly lit a nd control nois e a t night).

•

If s le e p a id is ne e de d, cons ide r ve ry s ma ll dos e s of ha lope ridol or a typica l a ntipsychotic a ge nt ins te a d of be nzodia ze pine s (unle s s pa tie nt ha s be e n pre s cribe d be nzodia ze pine s prior to a dmis s ion).

No

Dis c harg e g uide line s Dis cha rge is not a dvis a ble until e tiology of de lirium is cle a r, a nd e pis ode ha s re s olve d or s ignifica ntly improve d. Educa te fa mily re ga rding s igns a nd symptoms of de lirium a nd e ns ure tha t the te a m will be notifie d if pa tie nt fluctua te s from previous cognitive ba s e line. Dis continue us e of a ntipsychotic me dica tions or e ns ure tha t prima ry ca re phys icia n will s top me dica tions a t follow-up vis it.

Re que s t psychia try cons ulta tion or the he lp of a loca l de lirium expe rt This pa thway is a ppropria te for a dult pa tie nts (18 y & ove r) De lirium ca n pe rs is t for we e ks or months a fte r the ca us e s a re tre a te d

This pa thway is not exha us tive. Additiona l or a lte rna tive a s s e s s me nts, inve s tiga tions, ma na ge me nt s tra te gie s or tre a tme nts may be ne ce s s a ry. Clinic al judg e me nt & de c is io ns s ho uld be made by the appro priate re s po ns ible he alth c are pro fe s s io nal.

For a dditiona l informa tion vis it www. s cottis hde liriuma s s ocia tion.com

Figure 81 2 Diagnosis and treatment o delirium.

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TABLE 81-2 Common Medications Linked to Delirium

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Antia rrhythmics Disopyramide Lidocaine Procainamide Quinidine Antibiotics Acyclovir Amphotericin B Aminogylcosides Cephalosporins Chloroquine Chloramphenicol Ganciclovir Isoniazid Me loquine Metronidazole Ri ampin Sul onamides Tetracyclines Vancomycin Voriconazole Anticholinergics Atropine Benztropine Scopolamine Trihexyphenidyl Anticonvulsants Ethosuximide Carbamazapine Gabapentin Phenobarbital Phenytoin Primidone Valproic acid Antiemetics Chlorpromazine Metoclopramide Promethazine Prochlorperazine

Antidepressa nts Tricyclics Phenelzine Trazodone Paroxetine Fluoxetine Citalopram Escitalopram Mirtazapine Antihista mines Diphenhydramine Hydroxyzine Antihypertensives Clonidine Ni edipine Methyldopa Propranolol Timolol Anti-inflamma tory Agents Corticosteroids Ibupro en Indomethacin Naproxen Sulindac Antipsychotics Clozaril Low-potency typicals Quetiapine Olanzapine Dopa mine Agonists Amantadine Bromocriptine Levodopa Selegiline HIV Medica tions E avirenz Nevirapine Zidovudine

PRACTICE POINT Beware o benzodiazepines • Be wary o using benzodiazepines to treat agitation in a delirious patient who is not in alcohol or benzodiazepine withdrawal. Benzodiazepine use can be like ad d in g u e l to t h e ire, m akin g ag it at ion worse an d p rolon gin g d e lirium .

Opioids can also contribute to delirium. Reduce the dose o opioids and consider nonopioid methods o pain management. Tramadol should be used with caution, as this medication has also 568

H2 Blockers Cimetidine Famotidine Ranitidine Immunomodulators 5-Fluorouracil Cyclosporine Chlorambucil I os amide Inter eron Interleukin-2 Tacrolimus Tamoxi en Vinblastine Vincristine Muscle Relaxants Baclo en Cyclobenzaprine Narcotics All ormulations Other Medications Digitalis preparations Dipyridamole Disul iram Lithium Pregabalin Propylthiouracil Sildena il Timolol ophthalmic Tramadol War arin Seda tives Barbiturates Benzodiazepines Nonbenzodiazepine hypnotics Sympathomimetics Amphetamine Ephedrine Phenylephrine Theophylline

been associated with the development o delirium. I a patient with a patient-controlled analgesia (PCA) pump becomes delirious, discontinue its use promptly. Patients who have dif culty remembering and attending to their surroundings will o ten unintentionally overuse the PCA, or alternatively, may not be organized and attentive enough to use the pump when indicated. In addition, mounting anxiety rom delirium may result in renetic use o the PCA, which, in turn, can worsen delirium. Use nurse-administered intravenous or oral agents instead. The management o pain in the delirious patient is a delicate balancing act. Just as the overuse o opioids can cause delirium, poorly controlled pain can precipitate or worsen delirium. Care ul assessment and treatment o the patient’s pain are vital.

C H A P T E R 8 1 D e l i r i u

•    There is little evidence that any medication can prevent or shorten the duration o delirium. •    Benzodiazepines should be avoided unless speci ically indicated (ie, alcohol withdrawal, serotonin syndrome) as they o ten worsen delirium. •    Antipsychotics are o ten used to treat the ollowing symptoms associated with delirium: •    Agitation or violence that places the patient or sta at risk o harm. •    Hallucinations, delusions, ear ulness, or sleep cycle disruption. •    Be ore starting an antipsychotic: •    Review/calculate QTc on ECG. •    Check serum potassium (K+), magnesium (Mg ++), and calcium (Ca++). •   I QTc >450 msec in men or >470 msec in women, weigh the risks and bene its o starting a QTc-prolonging medication, such as an antipsychotic and do the ollowing: •   I possible, reduce dose or discontinue/substitute other prescribed medications that may be contributing to prolonged QTc. •   Keep serum electrolytes K+ >4 and Mg ++ >2 mEq/L††. Normalize serum calcium. •   Antipsychotic use or the treatment o agitation in delirium is a temporary measure; ongoing use should be re-assessed daily. •   Select an antipsychotic based on e icacy, available administration route (ie, by mouth [po], intravenous [IV], and intramuscular ormulations [IM]) and cost. •   Use the lowest e ective dose to manage symptoms (eg, starting dose o haloperidol: 1–2 mg IVor 2–5 mg po in adults with severe agitation, with 50% dose reduction or rail or elderly patients). Repeat within 30 minutes i no e ect is seen. •   IM and IVadministration o haloperidol results in double the peak drug levels compared to oral administration (ie, 1 mg o haloperidol IV= 2 mg po). •   Monitor or extrapyramidal side e ects, such a sakathisia, dystonia, and Parkinsonian symptoms. •   Akathisia—is a subjective sense o “inner restlessness” or “inability to stay still”; this side e ect can be mistaken or worsening agitation because o the patient’s motor restlessness. •   Dystonia—includes oculogyric crisis (contraction o extraocular muscles resulting in sustained deviation o the eyes), or dystonia o neck or trunk muscles or o pharynx. Dystonia is very rightening, pain ul and can be li e threatening (particularly pharyngeal dystonia). It should be treated immediately with diphenhydramine 25–50 mg IVor IM, or benztropine1–2 mg IVor IM. •   Examinemuscular tone or cogwheel rigidity or tremor daily in elbow and wrist joints. •   I side e ects occur and the patient is on a high potency antipsychotic (such as, haloperidol or risperidone), lower the dose, or stop the medication, or consider switching to a lower potency medication (such as, olanzapine or quetiapine). •   Continue to search or and treat the underlying causes o delirium. •   Once the patient’s agitation and sleep disruption have ully resolved, taper antipsychotic medication over a period o days with a goal, when easible, to discontinue all antipsychotics be ore hospital discharge.

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TABLE 81-3 Considerations When Using Medications or Symptomatic Treatment in Delirious Patients†

No medication is approved by the U.S. Food and Drug Administration or the treatment o delirium. †† This recommendation comes rom Hu man J, Stern T, Januzzi J. The Psychiatric Management o Patients with Cardiac Disease. In: Stern T, Fricchione G, Cassem N, et al (eds.). Massachusetts General Hospital Handbook o General Hospital Psychiatry, 5th ed. Philadelphia: Mosby, 2004, pp. 547–569. In our own experience, a magnesium level o > 2 mEq/L is hard to achieve. A more realistic goal may be to keep magnesium levels above the low end o normal (ie, > 1.3 mEq/L), aiming or the higher end o normal (ie, 2 mEq/L). †

■ INFECTION, ELECTROLYTE IMBALANCE, AND ORGAN FAILURE Look or new sources o in ection and per orm an appropriate workup. A relatively minor urinary tract or dental in ection in a mildly demented elderly patient can trigger delirium. Electrolyte abnormalities such as hypo- and hypernatremia or hypo- and hypercalcemia are relatively common. Screen or these and correct any imbalances. Organ ailure, including pulmonary compromise with hypoxia and hypercarbia, uremia, and hepatic ailure are all potentially reversible causes o delirium. I history and physical examination are consistent with a neurologic condition (eg, history o headache, head trauma, anticoagulation, ever, sti neck, or ocal neurologic ndings on physical exam), obtain brain imaging and lumbar puncture.

■ NONPHARMACOLOGIC MANAGEMENT OF DELIRIUM 1. Orient patients by providing environmental cues. Delirious patients have great dif culty acquiring and retaining new in ormation. Because disorientation is common, sta and amily should regularly remind patients o where they are and why

they are in the hospital. Provide glasses and hearing aids i a patient has visual or auditory impairment. Familiarize patients with their surroundings by placing amily photos, clocks, and calendars within their view. Encourage amily members to visit or stay with patients, and make every e ort to provide delirious patients with private rooms so that amily members can stay overnight. Limit room and sta changes as much as possible. 2. Reduce overstimulation. Reduce noise, loud talk, and laughter. Delirious, disoriented individuals can easily assign sinister meanings to these random stimuli. Urge sta to use a quiet voice and to interact calmly with the delirious patient. Turn o the TV i the patient is not attending to it. Try music that may be soothing to the patient, based on their music pre erences. 3. Reduce restraint use. Physical restraints can o ten worsen anxiety, make patients eel unsa e, and contribute to delusional belie s about persecution. Round the clock observation o the patient by sta , amily, or riends can minimize the need or restraints, especially when observers are skilled at redirecting 569

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and reassuring the patient. Remember that a wide variety o medical equipment, including catheters and intravenous lines, unction as restraints and may exacerbate agitation. Avoid their use as much as possible. I medical equipment is the ocus o an illusion (eg, perceiving an IV line as a snake), try to disguise its presence by hiding or wrapping it in gauze. 4. Improve sleep-wake cycle. Strong circadian signals combat delirium-associated sleep disturbance. Thus, treatment o delirium should include opening window blinds during the day and shutting o or dimming lights at night. Instead o sedative medications, use back massage, warm milk or herbal tea, and relaxing music or white noise to help patients sleep at night. Minimize noise and patient care-related interruptions during night time. 5. Mobilize early. Get patients out o bed and involved in activity and mobilization as soon as possible. Studies have shown that decreased sedation and early mobilization dramatically reduce the prevalence o delirium with a commensurate drop in length o stay, even among critically ill individuals. I patients are bedbound, encourage exercise and activity that can be per ormed in bed, such as exercise bands and simple puzzles or games. 6. Maintain nutrition, hydration, and oxygenation. Monitor nutrition and hydration status, and maintain adequate oxygenation. Dehydration and hypoxia are common contributors to delirium. Ensure regular bowel movements and monitor urinary output, as constipation and urinary retention can both lead to agitation.

■ PHARMACOLOGIC MANAGEMENT OF DELIRIUM The treatment o an agitated or combative delirious patient is particularly challenging. Treatment o agitation should begin with nonpharmacologic measures, such as reassurance and redirection o the patient. Medications should be considered only i nonpharmacologic management ails to control agitation and threatens the sa ety o the patient and sta , or i patients are experiencing distressing delusions or perceptual disturbances. The use o antipsychotics or the treatment o delirium has not been approved by the Food and Drug Administration and remains o -label. There are a limited number o randomized clinical trials examining the pharmacologic management o delirium. Meta-analysis o existing studies suggests that there is no evidence that antipsychotic medications decrease the duration or severity o delirium or the length o stay in the ICU or hospital. Current evidence suggests that there is no signi cant di erence between low-dose haloperidol (≤3 mg/d) and atypical antipsychotics (such as olanzapine and risperidone) in decreasing the severity o delirium symptoms or in the incidence o extrapyramidal side e ects (EPS). Higher daily doses o haloperidol are associated with an increased risk o EPS and may worsen delirium. Atypical antipsychotics may be associated with less EPS, but this has not been adequately evaluated in published randomized controlled trials o delirious patients. The main advantages o haloperidol are its availability in intravenous and intramuscular ormulation, as well as its low cost. Prolongation o the electrocardiographic QT interval leading to torsade de pointes is a rare, but recognized, complication o all antipsychotic agents, and can be made more severe by intravenous administration o these drugs, changes in liver or kidney unction, and concomitant use with other QT-prolonged medications. Monitor the QTc regularly and titrate medications accordingly. Table 81-3 includes current guidelines or the use o antipsychotics in the delirious patient. Benzodiazepines should be avoided as a treatment or agitated delirium, except in GABAergic-withdrawal-related delirious states, where benzodiazepines are a rst-line treatment. Benzodiazepines 570

may make con usion and agitation much worse. The use o asneeded bolus, rather than continuous in usion, o sedation medications in the ICU has been associated with signi cantly ewer days o delirium. There is no convincing evidence to support any other pharmacologic approach to prevent the occurrence, or decrease the duration or severity o delirium once it has started.

■ THE ROLE OF PSYCHIATRIC CONSULTATION The hospital physician will invariably encounter cases in which the diagnosis or management o delirium are not straight orward, even a ter ollowing the guidelines presented in this chapter. In such cases, psychiatric consultation should be obtained. The psychiatric consultant can help clari y an ambiguous diagnosis, recommend urther diagnostic studies, or suggest alternative management strategies when those suggested above prove insuf cient.

PRACTICE POINT 30% to 40% o delirium cases may be preventable through nonpharmacologic approaches • It is easier to prevent than to treat delirium. • Address modi able risk actors in patients at high risk or delirium.

■ PRIMARY PREVENTION Delirium is o ten preventable. The most e ective way to treat delirium is to prevent its occurrence. The nonpharmacologic interventions described above have been shown to decrease the incidence o delirium when used preventatively. In a landmark study o elderly patients admitted to a general medical service, a multicomponent intervention, including regular orientation and cognitive stimulation, use o nonpharmacologic methods to promote sleep, early mobilization, correction o dehydration, and proactive use o visual and auditory aids, signi cantly reduced the incidence o delirium to 9.9% in the intervention group (n = 429), compared to 15% in those who received usual care (n = 429). This striking reduction in the development o delirium suggests that these strategies should be considered a part o routine care or all high-risk hospitalized patients. Other interventions have been studied in randomized controlled trials. A study o mechanically ventilated patients in the ICU showed that early introduction o routine, daily physical and occupational therapy reduced the median number o days o delirium per patient rom 4 in control patients (n = 55) to 2 in study patients (n = 49). An Australian study demonstrated a decreased incidence o delirium when geriatric patients received rehabilitation services at home instead o in the hospital. The patients who received home rehabilitation were ollowed by a team that included physicians who proactively assessed and treated medical conditions such as in ection in order to avoid readmission to the hospital. Other preventative strategies include avoiding exposure to known deliriogenic medicines, especially anticholinergics and benzodiazepines, in patients at high risk or delirium. A detailed history o alcohol, benzodiazepine, and barbiturate use and prophylactic treatment with a benzodiazepine can also prevent withdrawalrelated delirium in susceptible patients. Early studies have suggested a role or a number o pharmacologic drugs including antipsychotics, cholinesterase inhibitors, and melatonergic agents or the prevention o delirium. However, convincing evidence is lacking or these drugs and routine use is not recommended. A number o small studies suggested that oral haloperidol and other antipsychotics might be use ul in delirium prophylaxis; however, meta-analyses o studies regarding delirium

■ COMPLICATIONS Delirium is associated with signi cantly increased morbidity and mortality. It can lead to a host o complications, including aspiration pneumonia, pressure ulcers, trauma rom accidental alls or removal o medical devices, and decreased oral intake, all o which may contribute to an increased length o stay. The cumulative 1-year mortality rate or elderly patients with delirium has been reported to be 38%, compared to 21% or control subjects admitted to a community hospital. Studies have also ound an association between delirium and subsequent long-term cognitive impairment. One study o nondemented patients aged 65 years and older reported that 18.1% o delirious patients were diagnosed with dementia by 3-year ollow-up, compared to 5.6% o nondelirious patients. As discussed previously, the presence o mild cognitive impairment is a known risk actor or the uture development o delirium. A prospective cohort o 821 critically ill patients demonstrated signi cant levels o cognitive impairment o survivors at 3 and 12 months o ollow-up; longer duration o delirium was independently associated with worse global cognition at o these time points. Whether delirium actually causes long-term cognitive decline, or whether its association with cognitive decline can be attributed to pre-existing subclinical neurologic pathology, is currently being investigated. Research does demonstrate that delirium is associated with psychological sequelae, including anxiety disorders, related to the rightening nature o perceptual experiences during delirium. A systematic review o the literature reported that the rate o clinically signi cant post-traumatic stress disorder (PTSD) symptoms up to 2 years a ter in-hospital delirium was 14%, with PTSD rates in ICU survivors even higher at 15% to 25% at 6 to 12 months a ter critical illness. Clinically signi cant depressive symptoms occurred in 31% o previously delirious patients. CONCLUSION Delirium is a medical emergency that can o ten be prevented i at-risk patients are identi ed and speci c interventions are put in place. Although it is common in hospital settings, it may be missed on rounds, as delirious patients are o ten quiet and withdrawn. In order to identi y hypoactive delirious patients, the treatment team must maintain a high index o suspicion and actively look or de cits in attention and cognition. Once a diagnosis o delirium has been made, triggers and sustaining actors must be identi ed

has 24-hour supervision been arranged? • Have sta or amily caretakers been educated in steps to prevent and manage delirium? • Have deliriogenic medications, such as anticholinergics and benzodiazepines, been stopped? • Have antipsychotic agents prescribed or the management o agitated delirium been stopped? Ideally, these medications should be stopped be ore discharge, as the risks o long-term antipsychotic use in older patients with dementia include increased risk o stroke and sudden death, extra pyramidal side e ects, metabolic syndrome, and unnecessary expense. It is best to taper these medications slowly. I discharge occurs be ore this can be accomplished, it is important to communicate the plan or tapering and discontinuing antipsychotics a ter hospital discharge must be communicated to the patient’s primary provider.

C H A P T E R 8 1 D r i u

• For patients with persisting delirium at the time o discharge,

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and reversed, and speci c nonpharmacologic treatments should be administered. Antipsychotic medications may be indicated i severe agitation ails to respond to nonpharmacologic measures or i delusions or perceptual disturbances are present. In ambiguous or dif cult cases, psychiatric consultation should be obtained. The prevention and prompt identi cation and management o delirium may signi cantly reduce length o stay, morbidity, mortality, and health care costs. It can also save patients, amily members, and caretakers considerable su ering and distress.

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prevention in perioperative or critically ill patients do not support this. A randomized controlled trial o the cholinesterase inhibitor rivastigmine, given as an adjunct to haloperidol treatment in critically ill delirious patients in the Netherlands, was stopped early due to increased mortality in the rivastigmine group. Although this di erence in mortality did not reach statistical signi cance, the median delirium duration in the rivastigmine group was signi cantly longer than in the placebo group. Randomized controlled trials employing melatonin and other melatonergic agents have also resulted in mixed ndings. A care ully conducted randomized controlled trial o melatonin in patients undergoing hip racture repair in the Netherlands did not demonstrate any reduction in the incidence o postoperative delirium. Another trial o a melatonin agonist, ramelteon, in medically ill patients in Japan demonstrated a lower incidence o delirium, but this single study requires replication.

SUGGESTED READINGS American Geriatrics Society Expert Panel on Postoperative Delirium in Older Adults. American Geriatrics Society abstracted clinical practice guideline or postoperative delirium in older adults. J Am Geriatr Soc. 2015;63:142-150. Barr J, Fraser GL, Puntillo K, et al. Clinical practice guidelines or the management o pain, agitation, and delirium in adult patients in the intensive care unit. Crit Care Med. 2013;41:263-306. Gusmao-Flores D, Martins JC, Amorin D, Quarantini LC. Tools or diagnosing delirium in the critically ill: is calibration needed or the less sedated patient? Intensive Care Med. 2014;40:137-138. Hshieh TT, Yue J, Oh E, et al. E ectiveness o multicomponent nonpharmacological delirium interventions: a meta-analysis. JAMA Intern Med. 2015;175:512-520. Inouye SK, Westendorp RG, Saczynski JS. Delirium in elderly people. Lancet. 2014;383:911-922. Neto AS, Nassar AP Jr, Cardoso SO, et al. Delirium screening in critically ill patients: a systematic review and meta-analysis. Crit Care Med. 2012;40:1946-1951. Pandharipande PP, Girard TD, Jackson JC, et al. Long-term cognitive impairment a ter critical illness. N Engl J Med. 2013;369:1306-1316. Young J, Murthy L, Westby M, Akunne A, O’Mahony R, Guideline Development Group. Diagnosis, prevention, and management o delirium: summary o NICE guidance. BMJ. 2010;341:c3704.

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82

CHAP TER

Diarrhea Danielle B. Scheurer, MD, MSCR, SFHM Talat H. Raja, MD

CASE 82-1 A previously healthy 45-year-old man sustained a motor vehicle accident resulting in multiple bone ractures and a traumatic brain injury. As such, he was admitted to the intensive care unit, intubated, sedated, and later taken to the operating room or repair o multiple ractures. On hospital day 3, the surgical team requested a medicine consultation or assessment and management o diarrhea. The patient had no history o diarrhea prior to admission, and his symptoms began on hospital day 2. The diarrhea was loose, semi ormed, our to six times a day, without blood, mucus, or pus. The patient remained intubated and sedated. His vital signs were stable, he was a ebrile, and his abdominal exam was benign. He received eedings via a nasogastric tube, reaching nutritional goals. His medications included subcutaneous heparin prophylaxis, a proton-pump inhibitor, docusate, senna, intravenous propo ol, and intravenous morphine. He had normal laboratory tests, including a white cell count o 8000 per cubic millimeter.

INTRODUCTION

Key Clinical Questions 1

What questions in the diarrhea history will guide the need or diagnostic testing?

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What is the yield o commonly ordered diagnostic stool tests?

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What is a practical algorithm to guide rational diagnostic stool testing?

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What are practical supportive therapies or hospitalized patients with diarrhea?

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What are the key measures or preventing the spread o in ectious diarrhea?

■ DEFINITION The typical adult eating a Western diet excretes 100 to 200 g o ecal matter a day, consisting o water, electrolytes, indigestible matter, unabsorbed ood, intestinal secretions, epithelial cells, and enteric bacteria. Diarrhea is de ned as an abnormal increase in excretion o ecal matter to >200 g a day. Nosocomial diarrhea is an acute diarrheal episode not present during admission and occurring a ter >3 days o hospitalization. The epidemiology o acute nosocomial and acute communityacquired diarrhea are quite disparate; this chapter will ocus on the ormer. The usual bacterial, viral, and protozoal culprits in community-acquired diarrhea are rare in nosocomial diarrhea. They will be mentioned in this chapter as patients may acquire them prior to hospital admission, but they will be appropriately deemphasized as causes o diarrhea in hospitalized patients.

■ INCIDENCE Diarrhea is a common a iction in the hospital, occurring in 33% to 50% o inpatients. Patients who acquire diarrhea while in the hospital have longer lengths o stay and higher mortality than those who do not. Diarrhea also is associated with more diagnostic testing (stool studies, imaging exams, electrolyte monitoring) and more interventions (intravenous uids, electrolyte supplementation, and medication adjustments). It also creates cleanliness and quality-o -li e issues, especially in patients that are not independent in mobility and sel -care. The di erential diagnosis or diarrhea in hospitalized patients is extensive, but is most conveniently dichotomized into in ectious and nonin ectious etiologies. INFECTIOUS DIARRHEA There are >200 million cases o in ectious diarrhea in the United States each year, resulting in 1.8 million hospitalizations. Most are acquired rom ecal-oral transmission, person-to-person contact, or ood and liquids (although the latter is highly unusual in the hospital setting). Alteration o intestinal microbiome appears to play a role 572

TABLE 82-1 Transmissibility of Bacterial Diarrheal Diseases Organism Salmonella typhi Nontyphoidal Salmonella Campylobacter Escherichia coli 0157:H7 Shigella

Usual Transmission Person-to-person ood Environmental animal reservoir Food Food Person-to-person ood

Inoculum Required to Cause Disease High Low Low Low Low

C H A P T E R 8 2 D i a r r h

The bacterial pathogens that cause community-acquired diarrhea are rarely acquired in the hospital setting, although they may be already present in patients hospitalized with diarrhea acquired in the community. In the United States, there are 5.2 million cases o bacterial diarrhea, 46,000 hospitalizations, and 1500 deaths annually. The majority o these occur in outpatients as a result o ood-borne transmission. Person-to-person transmission is less common and usually occurs with pathogens that only require a small inoculum to cause disease (Table 82-1). Bacterial etiologies make up 1.5% to 5.6% o cases o community-acquired diarrheal illness. The usual bacterial suspects include Salmonella spp (1.8%), Shigella spp (1.1%), Campylobacter spp (2.3%), and Escherichia coli 0157:H7 (0.4%). Salmonella typhi is almost always acquired by person-to-person transmission, rom an acutely in ected or chronic carrier, but rarely can be transmitted through ood or water. Such was the case o “Typhoid Mary” Mallon, a healthy Irish immigrant cook who, as an asymptomatic carrier, in ected at least 22 people over 7 years be ore being identi ed. The rarity o S. typhi outbreaks in the United States is a re ection o exemplary hygiene and sewage standards. Transmissibility o the organism depends on the density o the organism in the in ected person, and the in ectivity o the strain. Generally, a high inoculum is required to result in clinical symptoms, based on voluntary experimental ingestions. Diarrhea is a variable nding in typhoid ever; some patients may have constipation. Nontyphoidal S. spp, on the other hand, are rarely transmitted person-to-person, usually derive rom an environmental animal reservoir ( arm animals), and require a much lower inoculum to cause clinical in ection. Campylobacter spp, similar to nontyphoidal S. spp, are rarely transmitted person-to-person, and are usually linked to contaminated ood sources (meat, dairy, or water). Although a small inoculum is required or in ection, widespread outbreaks rarely occur, because most patients remain asymptomatic. E. coli 0157:H7 transmission also usually occurs through contaminated ood (meats or ertilized ruits/vegetables), although secondary person-to-person transmission may subsequently occur. The in amous large outbreak in the early 1990s was linked to

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contaminated hamburger, and secondary in ection was rampant, occurring in up to 20% o close contacts. Shigella spp spreads rom person to person or through contaminated ood, but has no environmental reservoir (similar to S. typhi). It is highly contagious, with a low density o inoculum required to result in clinical in ection. It there ore commonly causes outbreaks, usually within households and day care centers. Occasional patients are seen with an antibiotic-associated hemorrhagic colitis that mimics C. dif cile colitis. A small series o patients with this non-Clostridium dif cile antibiotic-associated hemorrhagic colitis ound that most cases were caused by Klebsiella oxytoca, which produces a cytotoxin leading to epithelial cell death. Patients have segmental mucosal ulceration and edema predominantly in the right and transverse colon. The diagnosis may be established by sending stool samples to the microbiology laboratory speci cally to culture or Klebsiella spp. Rarely, non-Clostridium dif cile antibioticassociated hemorrhagic colitis may be due to enterotoxigenic strains o Klebsiella pneumonia, Staphylococcus aureus, and type A Clostridium per ringens. Candida spp have also been implicated in nosocomial diarrhea. It is thought to cause a secretory diarrhea without evidence o colitis in critically ill or debilitated patients, but it is unclear how to treat or manage these patients.

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in most cases o in ectious diarrhea. Contagious spread by personto-person contact also includes transmission through omites, such as stethoscopes, bedside commodes, or other medical equipment. The vast majority o in ectious diarrhea in inpatients is caused by Clostridium dif cile. Clinical studies have shown that 12% to 32% o hospitalized patients develop diarrhea and that 75%) is not caused by in ection. Nonin ectious nosocomial diarrhea can be due to a host o insults, including side e ects o medical and nutritional therapy (drugs, oods, additives, enteral eedings, contrast agents, opiate withdrawal, radiation therapy), and new gastrointestinal pathology ( ecal impaction, in ammatory bowel disease, transplant rejection, GI bleeding, at malabsorption, and biliary obstruction).

■ SIDE EFFECTS OF MEDICAL AND NUTRITIONAL p

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As medications are a major o ender or nosocomial diarrhea, a careul review o medications is warranted (Table 82-2). The requency o antibiotic-associated diarrhea (AAD) ranges rom 2% to 25% (with no signi cant di erence between intravenous and oral antibiotics). The spectrum o disease caused by antibiotic-associated diarrhea can range rom uncomplicated loose stools to rank C. dif cile colitis. Risk actors or AAD include advanced age, immune suppression, gastrointestinal disease or previous gastrointestinal surgery, and severe comorbidities. Antibiotics lead to diarrhea via many di erent mechanisms. Disruption o gut ora results in osmotic or secretory diarrhea by disrupting the metabolism o carbohydrates, short chain atty acids, and bile acids, as well as impairing colonization resistance, resulting in a more avorable environment or diarrheagenic organisms. Probiotics have been thought to possibly prevent AAD, but the recent PLACIDE trial involving nearly 3000 hospitalized patients ound no evidence that probiotics prevented AAD or C. dif cile colits. New oods during the hospital stay can also result in diarrhea. O ending agents include sugar- ree gum or candy, and new oods with dairy content in patients with previously unrecognized lactose

TABLE 82-2 Medications Commonly Associated with Nosocomial Diarrhea Antibiotics

Gastrointestinal agents

Cardiovascular agents NSAIDs Supplements

Immunosuppressive agents

Other agents

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Clindamycin Erythromycin Cephalosporins Ampicillin H2 blockers Proton pump inhibitors Antacids (magnesium-containing) Misoprostol Digitalis Quinidine All types (including aspirin) Magnesium Phosphorus Elixir additives (sorbitol/lactose) HIVmedications (protease inhibitors) Chemotherapeutic agents Tacrolimus Cyclosporin Azathioprine Colchicine (dose limiting) Levothyroxine (dose related) Theophylline

intolerance. Medication elixirs o ten contain substances such as sorbitol, which causes osmotic diarrhea. Enteral eedings are also a common cause o osmotic diarrhea, which occurs in 15% o patients upon initiation o enteral eedings. In patients taking narcotics be ore their hospital stay, a reduction or cessation o their usual amount can present with diarrhea as a symptom o opiate withdrawal. Since nausea and vomiting o ten accompany opiate withdrawal, vomiting up oral opiates may be an important exacerbating actor. Oral contrast agents used in imaging present an osmotic load to the gut that can result in transient diarrhea. Radiation therapy in the abdominal and pelvic region can cause both acute and chronic diarrhea. The symptoms o acute radiation enteritis generally start during or shortly a ter radiation therapy, and usually improve within 2 to 6 weeks o cessation o the radiation, but may persist long-term.

■ NEW GASTROINTESTINAL PATHOLOGY A number o new diagnoses during the hospital stay can result in diarrhea. Fecal impaction, especially in the elderly, psychiatric patients, and immobilized patients receiving high doses o opiates without an adequate bowel regimen, can develop diarrhea due to leakage around the impaction. New-onset in ammatory bowel disease should be entertained in cases o in ammatory diarrhea or which in ectious causes have been ruled out. Bone marrow transplant patients can present with diarrhea as a symptom o gra t versus host disease. GI bleeding can present with diarrhea, although the color o the stool should trigger an evaluation or bleeding. Fat malabsorption resulting rom a new small bowel or pancreatic dysunction can result in steatorrheic diarrhea. Biliary tract obstruction can result in bile-acid-associated diarrhea. HISTORY The onset, duration, requency, color, consistency, and character o the diarrhea, as well as associated symptoms, provide clues to its etiology. The degree o volume depletion should be assessed (thirst, urine color and amount, lethargy). Patients should be queried about epidemiological risks or in ectious diarrhea (health care or day care attendance or employment, pet or arm contacts, unpasteurized or raw oods, recent sick contacts). Medications should be reviewed to identi y potential causes o drug-induced diarrhea. In ectious diarrhea is o ten accompanied by nausea, vomiting, ever, tenesmus, or abdominal pain, and the stool may be watery, malabsorptive, or dysenteric. Direct gross examination o the stool can be tremendously help ul in narrowing the di erential diagnosis. Black tarry stools usually indicate digested blood, usually rom the upper GI tract, and maroon, red, or pink stools indicate undigested blood, usually in the lower GI tract (or upper GI tract with rapid transit time). Greasy stools that oat indicate at malabsorption, and clay-colored stools point to biliary obstruction. PHYSICAL EXAM The physical exam should ocus on the vital signs, general appearance, and the abdominal and rectal exams. The patient should be assessed or ever, signs o dehydration, and hemodynamic instability. The abdomen should be examined or pain, distention, and peritoneal signs. The rectal exam should include testing or gross or microscopic blood. DIAGNOSTIC TESTING An approach to rational diagnostic testing is presented in Figure 82-1. Several stool tests are available to help determine the etiology o diarrhea, most o which are discussed below. Physicians should adhere to the 3-day rule o diagnostic testing or bacterial or

Infe c tio us Re d Flag s : Fe ve r Abdomina l pa in Immunocompromis e d Re ce nt a ntibiotics Ele va te d WBC

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Diag no s tic Te s ting : Fe ca l WBC or La ctofe rrin (if a va ila ble ) C. d iffic ile te s ting Ba cte ria l te s ting (for a ll a cute bloody dia rrhe a if hos pita lize d 50 at globules per high power eld. Qualitative testing correlates well with quantitative testing, which is rarely required in inpatients. Stool osmolality can be per ormed on a random stool sample. Normal values range rom 275 to 295 mosm/L. The measured stool osmolality can be compared to calculated stool osmolality (2 × [Na + K]) to determine i there is an osmolar gap. A gap (>50) indicates an osmotic diarrhea, usually due to carbohydrates (sodium citrate, magnesium citrate, laxatives, lactulose, or sorbitol) or at (mineral oil or castor oil). A stool osmolality >500 mg/dL is highly suspicious or actitious diarrhea (usually due to laxative abuse).

PRACTICE POINT

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Systemic mani estations associated with in ectious diarrhea are as ollows: Reactive arthritis (Salmonella, campylobacter, Shigella, Yersinia) Hemolytic-uremic syndrome (E. coli 0157:H7, Shigella) Thyroiditis, pericarditis, acute glomerulonephritis (Yersinia)

TREATMENT

■ STOP THE OFFENDING AGENT OR THERAPY A care ul review o new oods, additives, and medications may uncover an o ending agent to be discontinued. Antibioticassociated diarrhea usually responds to discontinuation o the agent.

TABLE 82-3 Treatment of Known or Suspected Bacterial Pathogens

Vibrio cholera

Escherichia coli 0157:H7 Escherichia coli (enterotoxigenic, enteroaggregative, or traveler’s diarrhea) Salmonella (nontyphoid)* Salmonella (typhoid)

Shigellosis Aeromonas Plesiomonas Escherichia coli (enteroinvasive) Noncholeraic vibrios* *Not recommended i uncomplicated.

Antibiotic Options/Duration Azithromycin 500 mg 3 d Erythromycin 500 mg our times a day or 3 d Doxycycline 300 mg (single dose) Tetracycline 500 mg our times a day or 3 d Azithromycin 500 mg 3 d Erythromycin 250 mg three times a day or 3 d Not recommended Cipro loxacin 750 mg 1-3 d Azithromycin 1000 mg (single dose) Ri aximin 200 mg three times a day or 3 d Cipro loxacin 500 mg 7 d Azithromycin 500 mg 7 d Duration 14 d i immunocompromised Cipro loxacin 750 mg 3 d Azithromycin 500 mg 3 d

C H A P 2 D i a r r h

PRACTICE POINT

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Treatment o bacterial causes o in ectious diarrhea is summarized in Table 82-3. Empiric treatment or suspected bacterial pathogens with cipro oxacin should be initiated in patients with acute ebrile dysentery, but only a ter a ecal sample has been sent. In patients without ever or rank dysentery, empiric treatment is not warranted. For established diagnoses, patients should be treated according to Table 82-3. In patients with uncomplicated nontyphoidal Salmonella diarrhea, treatment with antibiotics does not reduce the duration o illness or ever, but does increase relapse rates and prolongs ecal shedding. However, patients with known or suspected bacteremia (toxic appearance or high ever) should be treated to prevent septicemia. E. coli 0157:H7 in ection should not be treated with antibiotics, as this does not improve outcomes and increases the risk o hemolytic-uremic syndrome. E. coli O157:H7 should be suspected in patients with bloody diarrhea, abdominal pain, and minimal ever. Diarrhea related to ecal impaction usually requires a combination o mechanical and medical disimpaction. New symptomatic

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A trial o nothing by mouth or 24 hours is o reasonable diagnostic and therapeutic value. Osmotic diarrhea will improve with asting, secretory diarrhea will not. Therea ter, diet can be resumed and advanced as tolerated. Use o a lactose- ree diet, due to a transient lactase de ciency rom mucosal injury, is usually recommended, although data to support its use are limited. Although probiotics have not been shown to prevent antibiotic-associated diarrhea, they may have a role in the treatment o in ectious diarrhea, as a Cochrane review ound that probiotics reduced the mean duration o diarrhea by 24 hours in this setting. There is not quality evidence supporting their role in nonin ectious diarrheas. Patients who cannot tolerate oral hydration will need intravenous hydration. Isosmotic uids are pre erred, unless electrolyte abnormalities dictate otherwise. I warranted, repletion o potassium can usually be accomplished orally, but magnesium or phosphorus supplementation are generally pre erred intravenously, as they can be caustic to the gut and exacerbate diarrhea.

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IBD usually requires immunosuppressive agents and bowel rest to relieve symptoms. Treatment o opiate withdrawal symptoms and transplant rejection are beyond the scope o this chapter. Fat malabsorption warrants treatment o the underlying pancreatic or small bowel dys unction, and usually requires enzymatic supplementation to correct. Biliary obstruction requires investigation and relie o the obstruction.

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There is little evidence that probiotics are e ective in antibioticassociated diarrhea, but their use is widespread, and there is little data to suggest harm, except in immunocompromised patients. Diarrhea related to new enteral eeds can be reduced by changing to a lower osmotic agent, reducing the rate, or adding antimotility agents, as discussed below. Contrast-associated diarrhea is sel limited; treatment is supportive care until resolution. Radiationassociated diarrhea is also treated supportively, unless intolerable symptoms dictate temporary cessation o the treatment.

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In patients with uncomplicated nontyphoidal Salmonella diarrhea, treatment with antibiotics does not reduce the duration o illness or ever, but does increase relapse rates and prolongs ecal shedding. However, patients with known or suspected bacteremia (toxic appearance or high ever) should be treated to prevent septicemia. Treatment o E. coli 0157:H7 increases the risk o hemolytic uremic syndrome and should be avoided.

■ ANTIDIARRHEAL AGENTS Although hundreds o agents are claimed to relieve diarrhea, only three have Food and Drug Administration labeling to support their use. In general, antidiarrheal agents should be avoided in patients with suspected in ammatory diarrhea. These agents have been associated with prolonged ever with S. spp, hemolytic-uremic syndrome with E. coli 0157:H7, and toxic megacolon with C. dif cileassociated diarrhea. Loperamide (Imodium) inhibits peristalsis and has antisecretory e ects. Bismuth subsalicylate reduces symptoms o nausea, diarrhea, and abdominal pain in patients with traveler’s diarrhea, but its use in other types o diarrhea (especially nosocomial variants) is unstudied. Diphenoxylate (Lomotil) is an opiate agonist that is e ective at reducing stool volume. PREVENTION Hospitalized patients experiencing diarrhea have longer lengths o stay and higher mortality than those who do not. They undergo more diagnostic testing, monitoring, and interventions. It is o paramount importance to prevent nosocomial diarrhea i possible. Prevention o in ectious nosocomial diarrheas includes the usual hygiene provisions and universal precautions. Interventions to promote hand washing have been proven to reduce diarrheal episodes among children in institutions by 30% to 40%. 577

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The patient’s home diet and medications should be reviewed again on each care transition. Cessation or initiation o new oods, additives, or medications should be done with a care ul review o the risks and bene ts. Routine use o stool so teners in hospitalized patients is o ten unnecessary and may lead to diarrhea. I despite preventive interventions, a hospitalized patient does experience nosocomial diarrhea, a step-wise, rational approach to diagnostic testing should be initiated, as outlined in Figure 82-1. Therapeutic and supportive interventions should be initiated based on the diagnostic evaluation, in a timely and cost-ef cient manner.

2 days ago or abdominal imaging. The proton-pump inhibitor, colace, and senna were stopped, and the rate o his enteral eeds was reduced. His diarrhea resolved within 48 hours and no urther diagnostic testing was per ormed.

SUGGESTED READINGS Allen SJ, Martinez EG, Gregorio GV, Dans LF. Probiotics or treating acute in ectious diarrhoea. Cochrane Database Syst Rev. 2010;(11):CD003048. Allen SJ, Wareham K, Wang D, et al. Lactobacilli and bi dobacteria in the prevention o antibiotic-associated diarrhoea and Clostridium dif cile diarrhoea in older inpatients (PLACIDE): a randomised, double-blind, placebo-controlled, multicentre trial. Lancet. 2013;382:1249-1257. Bartlett JG. Antibiotic-associated diarrhea. N Engl J Med. 2002;346: 334-339.

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Based on the algorithm outlined in Figure 82-1, the patient’s diarrhea started in the hospital, had been present or 1 day, was occurring our to six times a day, and was brown and semi ormed. His medication list included docusate, senna, and a protonpump inhibitor, all o which can lead to diarrhea. He had recently received perioperative antibiotics or the prevention o surgical site in ections, but was on no current antibiotic therapy and he was without any other in ectious red f ags. He had also recently been initiated on enteral eedings and had received oral contrast

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Guerrant RL, Van Gilder T, Steiner TS, et al. Practice guidelines or the management o in ectious diarrhea. Clin In ect Dis. 2001;32:331-350. Pawlowski SW, Warren CA, Guerrant R. Diagnosis and treatment o acute or persistent diarrhea. Gastroenterology. 2009;136:1874-1886. Polage CR, Solnick JV, Cohen SH. Nosocomial diarrhea: evaluation and treatment o causes other than Clostridium dif cile. Clin In ect Dis. 2012;55:982-989. Thielman NM, Guerrant RL. Acute in ectious diarrhea. N Engl J Med. 2004;350:38-47.

83

CHAP TER

Disorders of the Eye Ala Moshiri, MD, PhD Prem S. Subramanian, MD, PhD

Key Clinical Questions 1

Which conditions should prompt emergent ophthalmologic consultation?

2

Which conditions require prompt imaging and/or consultation with neurologists or neurosurgeons?

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For hospital employees with viral conjunctivitis what are the recommendations to prevent nosocomial spread to hospitalized patients?

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What are the risks o topical corticosteroids in patients with allergic conjunctivitis?

INTRODUCTION Ophthalmologic concerns in the hospitalized patient all into two broad categories: signs and symptoms o the systemic condition or which the patient has been admitted, and unrelated but potentially urgent disorders o the eye that may threaten vision. While some o the conditions discussed in this chapter may relate to the ormer issue, our approach will be to describe common ophthalmologic disorders or which inpatient consultation is o ten considered, and to provide in ormation on appropriate triage and workup prior to obtaining the consultant’s opinion. In many cases, outpatient evaluation a ter the acute illness has passed may be more use ul, since the patient’s cooperation with subjective testing methods is much more reliable. Symptoms that may prompt urgent evaluation include red eyes (with or without pain), double vision, and subjective loss o vision. There are a number o bedside examination techniques that do not require specialized equipment but can yield important in ormation to narrow the di erential diagnosis and help determine the urgency o urther testing. The consulting physician should per orm a ocused but detailed eye history and physical examination prior to consulting an ophthalmologist. Time o onset, monocular or binocular nature, duration, and associated neurologic symptoms are especially important. Past medical and ocular history are relevant, as are recent interventions during the current hospitalization that might contribute to the visual complaints. The examination should ideally include best-corrected visual acuity (with glasses) measured or each eye, either with a near reading card, wall-mounted distance chart, or smartphone app. It should be noted whether the pupils are equal in size and reactive to illumination. Abnormal extraocular movements may be seen with new binocular double vision. Peripheral vision testing with a small red object (pinhead, marker cap) can detect up to 75% o clinically relevant de cits. Finally, a hand-light examination should be done at the bedside to look or eyelid swelling or redness, conjunctival hyperemia and discharge, corneal clarity or haze, and gross iris and anterior segment abnormalities. I a direct ophthalmoscope is available, examination o the undus should be attempted. This is best done in dim lighting so that the pupil is somewhat large. I a normal appearance o the optic nerves, retinal vessels, and maculae can be con rmed, this can be very help ul. This requires some level o practice and pro ciency, but is within the scope o physical examination techniques o every physician.

PRACTICE POINT Ophthalmologic consultation is required or any condition that may cause severe and permanent vision loss, including • Corneal ulcers • Iritis • Acute angle glaucoma • Sudden visual loss • Orbital mass, including orbital abscess • Stevens Johnson Syndrome with mucosal involvement

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TABLE 83-1 Differential Diagnosis of Common Red Eye Complaints Iritis Common None Slightly blurred Circumcorneal Moderate Usually clear Small Sluggish Normal

Acute Glaucoma Uncommon None Severely blurred Circumcorneal Severe Steamy Mid-dilated Fixed Elevated

Corneal In ection Common Watery Usually blurred Circumcorneal Moderate to severe Variable Normal Normal Normal

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Incidence Discharge Vision Conjunctival injection Pain Cornea Pupil size Pupillary light response IOP

Conjunctivitis Very common Copious Una ected Di use None Clear Normal Normal Normal

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THE INFLAMED EYE

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■ EMERGENT CONSIDERATIONS

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In addition to the in ections detailed below, loss o sympathetic innervation may give a mild red eye rom vasodilation. When accompanied by ptosis (with or without miosis) as in Horner syndrome, this condition may be mistaken or ocular in ammation. Acute onset in a postpartum patient, with or without headache, may result rom carotid artery dissection, and MR or CT angiography must be perormed with consideration given to anticoagulation.

■ TEAR DYSFUNCTION SYNDROME (DRY EYE)

CASE 83-1 A 62-year-old woman is admitted or respiratory ailure rom a bacterial pneumonia. A ter 2 weeks o intubation in the intensive care unit on broad-spectrum antibiotics, her condition improves. She is extubated and trans erred to the medicine ward, where she reports eye irritation. Both eyes appear slightly red, and she reports some tearing and sensitivity to bright lights. Her vision is mildly blurred, and measures 20/25 in each eye with her reading glasses using a pocket visual acuity card. The remainder o her eye exam is essentially normal. This patient is likely su ering rom exposure keratopathy or corneal abrasion (Table 83 1). Under normal conditions, the ocular sur ace and eyelid glands produce aqueous, oily, and proteinaceous tear secretions essential or normal eye health. Insu cient lubrication is common in the setting o an intubated and sedated patient and can lead to breakdown o the sur ace o the cornea with subsequent corneal in ection and ulceration. For this reason, in such patients ICU protocols commonly include requent lubrication o the eyes with ointments to prevent ocular sur ace disease. Despite this e ort, mild damage to the cornea and conjunctiva, especially in a long hospitalization, may occur. Dry eye symptoms requently include eye irritation, blurry vision, oreign body sensation, and mild eye redness. Other patients at risk include those with known acial nerve paresis, recent anesthesia with insu cient eyelid taping during the procedure, and dementia. Reassurance and urther lubrication are warranted to relieve symptoms.

In contrast, a corneal ulcer presents as an opaque area in the cornea that may appear hazy or even white. The ulcer may have a signi cant mucopurulent exudate and will likely be very pain ul. The conjunctiva will requently be bright red (Figure 83-1). At the 580

bedside, the physician may use uorescein dye to look or an epithelial de ect. I corneal staining occurs, then the potential or corneal ulceration is high, even i an in ltrate is not yet seen and pain is minimal. Ophthalmologic consultation is required. Corneal ulcers may cause severe and permanent vision loss. The patient must be seen by an ophthalmologist that same day or culture o the corneal sur ace and broad-spectrum topical antibiotic therapy to prevent corneal per oration and endophthalmitis, which requently will lead to loss o the eye. The ophthalmologist may prescribe orti ed topical antibiotic drops to be applied every 30 to 60 minutes around the clock or the rst 24 to 48 hours, and the nursing sta must be made aware o the importance o adherence to this very demanding but e ective medical therapy.

■ CONJUNCTIVITIS

CASE 83-2 A 22-year-old man is admitted or respiratory distress attributed to an acute asthma attack. He is treated overnight with nebulized adrenergic agonists that are gradually weaned and prescribed systemic steroid therapy. It is also noted that he has mild eczematous changes on his hands that are not new. His roommate

Figure 83 1 Corneal ulcer with typical white exudate at the corneal limbus and severe conjunctival injection.

notes that he has had red eyes or the past 2 days, which have been itching and tearing as well. There has been no crusting o the eyelashes upon waking up and there is no rank pain. The eyes are mildly irritated, but itching has been the prominent eature. The skin beneath his eyelids is also slightly hyperpigmented. He has had similar episodes o red eyes be ore, which had resolved without serious complication. This case illustrates a classic example o allergic conjunctivitis. Severe itching is the most prominent symptom. Frequently, there will be generalized hyperemia (redness) o the conjunctiva and mild to moderate tearing (Figure 83 2). Visual blurring, i present, is mild and attributable to the tearing. Eye rubbing is typical, and the patient may have symptoms o allergic rhinitis as well, with associated rubbing o the nose. This rubbing can sometimes lead to mild eyelid edema and temporary hyperpigmentation (also known as allergic shiners, raccoon eyes) and a crease on the nose rom manipulation as well. Common associations are with asthma, eczema, or history o other atopy. Symptoms can be managed with arti cial tear lubricants and cool compresses i mild to moderate. I symptoms are severe or persistent, inpatient consultation with an ophthalmologist may be warranted, and treatment may require immune modulation with a topical antihistamine, mast cell stabilizer, or mild steroid. Topical corticosteroids should never be prescribed without active participation by the ophthalmologist, since untoward e ects may include promoting viral in ection (especially i there is a history o ocular herpes simplex) and intraocular pressure elevation.

■ VIRAL CONJUNCTIVITIS Viral conjunctivitis also presents with bilateral red eyes. However, the symptoms will o ten have started in one eye 1 to 2 days prior to starting in the ellow eye. O ten the eyes are very red with copious tearing, and the most prominent symptom is pain and burning. Mucous crusting o the eyelashes, especially in the morning, may be so copious as to preclude eyelid opening without manual assistance. A preauricular lymph node may also be palpated on exam and is relatively speci c or viral etiology. Symptoms tend to worsen or the rst ew days o in ection and generally resolve within 1 to 2 weeks. Household contacts may have had a recent URI or similar eye symptoms. Hand washing and contact precautions are crucial in preventing the spread o in ection. I hospital workers become in ected, they must be removed rom patient contact or at least 7

C H T E R 8 3 D i s o r d e r s o t h e E y

Figure 83 2 Allergic conjunctivitis with ormation o ollicles in the in erior conjunctival ornix. Inspection alone does not allow di erentiation rom viral in ection.

In contrast, bacterial conjunctivitis is o ten unilateral at presentation, which helps to distinguish it rom allergic and viral etiologies, but it may spread to both eyes via the hands to become bilateral. Common organisms include Neisseria, pneumococcus, Staphylococcus, Haemophilus inf uenzae, Moraxella, and others. Copious mucopurulent discharge is the most prominent eature. Pain and irritation with severe hyperemia may occur, but there should not be rank vision loss. Bilateral cases can be challenging to distinguish rom viral conjunctivitis, and an ophthalmologist should make this distinction. Debilitated patients are most prone to bacterial conjunctivitis, and suspicion or this diagnosis will be higher in such individuals. Treatment is usually with topical antibiotic ointments or drops, and may require cultures to determine the causative organism i the symptoms and signs are anything other than mild. Otherwise immunocompetent patients with unilateral disease may be treated empirically with topical uoroquinolones such as moxi oxacin or gati oxicin, both o which have broad-spectrum activity against the common organisms. I improvement is not seen within 48 hours, then cultures should be repeated and ophthalmologic consultation requested.

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days a ter symptoms start in the second eye to avoid nosocomial spread (spread to both eyes is very common even when in ected persons are very cautious).

PRACTICE POINT Conjunctivitis • Allergic conjunctivitis: Topical corticosteroids should never be prescribed without active participation by the ophthalmologist, since untoward e ects may include promoting viral in ection and intraocular pressure elevation. • Viral conjunctivitis: I hospital workers become in ected, they must be removed rom patient contact or at least 7 days a ter symptoms start in the second eye to avoid nosocomial spread. • Bacterial conjunctivitis: Treatment is usually with topical antibiotic ointments or drops, and may require cultures to determine the causative organism i the symptoms and signs are anything other than mild. I improvement is not seen within 48 hours, then cultures should be repeated and ophthalmologic consultation requested.

■ IRITIS

CASE 83-3 A 32-year-old man is admitted or acute persistent diarrhea leading to electrolyte imbalances. Workup o his gastrointestinal distress reveals abnormal ulcerations on colonoscopy consistent with inf ammatory bowel disease. During the rst hospital day, the patient reports blurry vision and photophobia in the le t eye only, which had started several days ago and has been gradually worsening. The eye is slightly red on examination and visual acuity is reduced to 20/40. The right eye is normal. This patient has anterior uveitis associated with inf ammatory bowel disease, but many autoimmune conditions can be associated with inf ammation o the eye. The most prominent eature is photophobia. O ten, patients are extremely sensitive to light; they may keep room lights o and blinds closed and even wear sunglasses indoors during an episode. Symptoms may be unilateral or bilateral, although the ormer is more common. Prior episodes also are common but vary in severity and laterality. Hyperemia is seen as a characteristic red ring o inf ammation 581

P A R T I V A p p r o a c h t o t h e

Figure 83 4 Mid-dilated pupil and corneal clouding (seen as loss o typical corneal sheen and dulling o corneal light re lex) in a case o acute angle closure.

around the edges o the cornea called limbal f ush (Figure 83-3). Diagnosis requires a slit lamp, as inf ammation cannot be diagnosed accurately without su cient magni cation o the anterior segment. Diagnosis, there ore, requires consultation with an ophthalmologist. While ocular inf ammation may be related to autoimmune conditions as in the case above, it may also be the result o in ection, and this must be ruled out in every case. The ophthalmologist will direct the appropriate investigations or possible in ectious etiologies. Serum tests or syphilis, Lyme disease, toxoplasmosis, and serological (eg, QFT-GIT) and/or skin testing or tuberculosis exposure are commonly per ormed. In addition, the ophthalmologist may recommend chest imaging or sarcoidosis, and i the review o systems suggests a possible undiagnosed autoimmune disease, serum testing or HLA-B27 may be per ormed as well. Rheumatologic consultation also may be appropriate.

have occurred in the past in the same eye, or in the ellow eye, usually in dim lighting, such as a movie theatre, since pupillary dilatation bunches up the iris tissue in the angle. The pupil is usually slightly larger than the ellow eye and is unreactive. The cornea is o ten cloudy because the elevated pressure impairs corneal endothelial unction, and this clouding makes it di cult to see the iris as clearly on the a ected side in comparison to the ellow eye (Figure 83-4). There should be no discharge or exudate. This condition occurs more commonly in women and is associated with ar-sightedness (hyperopia). The a ected eye may eel much more hard (be di cult to indent) in comparison with the ellow eye when gently palpated through closed eyelids. This is indicative o a severely elevated intraocular pressure, which is the cause o the potential optic nerve damage in glaucoma. I this diagnosis is suspected, immediate ophthalmic consultation should be made or prompt reduction o the intraocular pressure, initially with topical agents. Ultimately this condition requires laser peripheral iridotomy in the a ected eye as soon as possible, and in the ellow eye to prevent uture episodes. Importantly, the vast majority o patients with glaucoma do not su er rom angle closure attacks, but rather primary open angle glaucoma, which is largely asymptomatic and has no commonality with an angle closure attack as described above. A patient with red eyes and a history o “glaucoma” or which they take eye drops on a regular basis is almost certainly not having an acute angle closure attack.

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Figure 83 3 Characteristic limbal lush (redness) seen in cases o acute iritis.

■ ANGLE CLOSURE GLAUCOMA

CASE 83-4 A 68-year-old Caucasian woman is hospitalized or workup o chest pain. Spending most o her day in a dimly lit hospital room watching TV, she suddenly develops a red, pain ul, blurry right eye. The pain and redness worsen over the next hour and do not remit. During this period o time, the vision is pro oundly blurred. Visual acuity in the right eye is roughly 20/400, as she is able to only make out the largest letters on the pocket vision chart. The vision does not improve even with the use o her glasses, which are bi ocals that are somewhat thick. The patient reports she is arsighted and has been or many years. The patient also reports that she has had similar episodes in the past several years on occasion, sometimes in the le t eye, other times in the right eye, but never in both eyes simultaneously. She has attributed her symptoms to headache, and she has seen her primary care provider who diagnosed her with mild migraines and recommended Excedrin. Acute angle closure attacks are virtually always unilateral. It is a rare but vision-threatening condition and should not be missed. Prompt ophthalmology re erral is required to prevent permanent vision loss. It can be recognized by a very pain ul and red eye with pro oundly decreased vision. Patients commonly present with a severe headache on the a ected side, sometimes with associated nausea and vomiting; symptoms typically last or minutes to hours, not days or weeks. Similar episodes may 582

DIPLOPIA

■ EVALUATION The evaluation o diplopia must begin with determination o whether or not the symptoms are binocular. Monocular diplopia, that is, double vision in one eye only, is virtually never an ophthalmic emergency. Many entities can cause double vision in one eye, such as cataract, corneal pathology, or incorrect spectacle prescription. Binocular diplopia, double vision due to misalignment o the eyes, virtually always requires ophthalmologic evaluation or proper diagnosis and treatment. There ore, the rst question to the patient who complains o diplopia should always be, “does the double vision go away when you cover either eye?” I the answer is yes, then the patient has binocular diplopia and an ophthalmologist should be called when the remainder o the evaluation is complete. The diplopia may be intermittent or constant and may change with position o gaze. Patients should be asked about associated neurologic symptoms such as headache, nausea or vomiting, vertigo, and weakness or tingling.

This patient has an acute oculomotor (third cranial nerve) palsy. This may be due to ischemia o the nerve itsel secondary to chronic microvasculopathy related to hypertension and/or diabetes, a cerebral aneurysm, a mass impinging on the nerve, viral in ection, or trauma. The most concerning and potentially li e-threatening cause is aneurysmal compression. Aneurysms o ten arise at the junction o the internal carotid and posterior communicating arteries. Because the pupillary bers o the oculomotor nerve run peripherally within the nerve ascicle in the subarachnoid space, involvement o the pupil in an oculomotor

C H A P T E R 8 3 D i s o r d e r s o t

A 73-year-old man is admitted with double vision that resolves upon covering either eye. He reports that his symptoms started that morning. He has also noticed the right eyelid drooping since this morning. He has not had any prior eye problems except or using reading glasses, and has had cataract surgery in both eyes 3 years ago. He has hypertension controlled with two oral antihypertensive medications, and no other chronic medical conditions. On examination, his visual acuity is 20/25 on the pocket visual acuity chart in each eye with his reading glasses on. The examination o the pupils reveals that the right pupil is larger than the le t, and reacts more slowly than the le t as well. He reports that no eye doctor has ever noted a pupillary abnormality be ore. His extraocular movements demonstrate limitation in elevation, depression, and adduction o the right eye. When he is looking straight, the right eye is misaligned downward and temporally. In addition, the right eyelid hangs lower than the le t one (Figure 83 5). Visual elds tested by con rontation are grossly ull. Hand-light examination reveals normal-appearing anterior segments without hyperemia or opacity o the cornea. Direct ophthalmoscopy reveals normal-appearing optic nerves, retinal vessels, and maculae in each eye, though the view was easier in the right eye due to the enlarged pupil.

Trochlear ( ourth cranial nerve) palsy results in double vision with images appearing tilted with respect to one another. Diplopia with a torsional component should make the examiner suspicious o this diagnosis. On examination, the a ected eye appears higher than the ellow eye (hypertropia). This hypertropia increases when the a ected eye looks down or in toward the nose. Congenital partial trochlear nerve palsy is relatively common and o ten well-controlled until adulthood, when it may decompensate and cause mani est diplopia. The patient in this scenario will have a history o tilting the head toward the a ected side. This can be con rmed by looking at old photographs. Acquired trochlear paresis is also common and may be seen with even mild head trauma. It may also occur due to microvascular disease or cranial surgery. Abducens (sixth cranial nerve) palsy results in horizontal diplopia with images appearing side by side due to limitation or absence o abduction o the eye. When the patient is looking straight ahead, the a ected side may be misaligned with the eye pointing inward (esotropia). The remainder o the eye movements are normal. Frequently, the paresis is incomplete with some residual ability to abduct the a ected eye. Most cases o abducens nerve palsy in older adults are related to microvascular disease rom hypertension, diabetes, and hyperlipidemia, and these tend to resolve over weeks with no intervention. Care ul ophthalmologic ollow-up is required. I the abducens palsy does not resolve as expected, then tumor, arteriovenous stulas, and other intracranial processes must be ruled out.

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A patient with new third nerve paresis (see below), especially i painul and/or incomplete, must be evaluated with urgent neuroimaging. Less commonly, a sixth nerve paresis may be accompanied by ipsilateral ptosis and miosis consistent with Horner syndrome, localizing the process to the cavernous sinus; acute onset can arise rom cavernous sinus thrombosis or rapid tumor growth or hemorrhage.

nerve palsy is indicative o a cerebral aneurysm impinging on the nerve until proven otherwise. Vascular insults to the third nerve generally spare the pupil and thus can be distinguished clinically rom compressive lesions when the third nerve paresis is complete. An oculomotor nerve palsy a ects the superior rectus, in erior rectus, medial rectus, and in erior oblique muscles, in addition to the iris and ciliary body. The lateral rectus and superior oblique muscles are intact, and hence the eye may rest in a “down and out” position. Limitations in elevation, depression, and adduction are typical but requently are not complete, as some residual unction may persist.

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■ EMERGENT CONSIDERATIONS

■ ORBITAL DISORDERS Orbital masses may a ect globe position and disturb normal extraocular muscle action with resulting binocular diplopia. Thyroid eye disease, most commonly associated with Graves disease but which can also be present in some hypothyroid and euthyroid states, is an in ltrative disease o the extraocular muscles and orbital at that produces a congested orbit and proptosis. Unbalanced muscle involvement may lead to binocular diplopia. The diplopic patient must be asked about endocrine dys unction. Orbital masses, in addition to causing double vision, requently cause proptosis, which the astute observer will note even without exophthalmometry. I an orbital mass, including an orbital abscess, is suspected, prompt ophthalmic attention is required.

■ MYASTHENIA GRAVIS

Figure 83 5 Ptosis and ophthalmoparesis seen with third nerve palsy. Note dilation o the right pupil; this is not pharmacologic.

Myasthenia gravis is a disease o the neuromuscular junction with antibodies against the nicotinic acetylcholine receptors on the motor end plate. It requently presents (up to 75%) with ocular symptoms and may be limited to the eye. The most common presenting sign is ptosis, but any o the extraocular muscles may be involved. There ore, ocular myasthenia gravis may mimic virtually any cranial neuropathy. The pupil is virtually never involved in myasthenia gravis. Thus, pupillary abnormalities are a help ul clinical sign that can distinguish this disease process rom others. Diplopia in a patient with myasthenia typically waxes and wanes over the 583

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course o a day, improves with rest, and o ten has symptoms that have been occurring or the previous months or years. Ocular myasthenia may be unilateral or bilateral. I this disease is suspected, the ophthalmologist may use tests o atigability or the ice test to help in diagnosis, in conjunction with short-acting acetylcholinesterase inhibitors.

PRACTICE POINT

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Cranial Nerve Palsies • CN III: A patient with new third nerve paresis, especially i pain ul and/or incomplete, must be evaluated with urgent neuroimaging. • CN IV: Trochlear palsy results in double vision with images appearing tilted with respect to one another; it arises rom microvascular disease or neurosurgery. • CN VI: The Horner syndrome (a sixth nerve paresis accompanied by ipsilateral ptosis and miosis) localizes the process to the cavernous sinus; acute onset can arise rom cavernous sinus thrombosis or rapid tumor growth or hemorrhage.

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Both visual acuity and con rontation visual eld testing at the bedside must be per ormed and should help the clinician localize the vision loss to one eye or hemi eld. I there is bilateral loss, then the degree o asymmetry is important to record. The presence o other ocular and orbital signs (redness, ocular motility disturbance, eyelid swelling, ptosis) should be noted, as they will assist in anatomic localization. Pupillary reactions provide objective evidence o a erent visual loss and may direct the workup even when other data are con icting or unreliable. I an obvious visual disturbance (severe unilateral vision loss with a erent pupillary de ect, gross homonymous hemianopia) is not ound, then urther workup should be de erred and an ophthalmology consult obtained. Automated perimetric testing, dilated undus examination, photography and advanced imaging o the retina and optic nerve, and even re raction per ormed by the ophthalmologist will allow or a much more directed investigation, and may reveal other benign causes o vision loss (Table 83-2).

CASE 83-6 A 76-year-old man with long-standing congestive heart ailure is being treated with intravenous antibiotics or a communityacquired pneumonia. On hospital day 2, he complains o blurred vision in his le t eye. He is unsure i it came on suddenly but notices it when he tries to read or watch television. There is no eye pain, and the eye and periorbital area are normal without erythema, warmth, or tenderness. As in the assessment o diplopia, the rst question to answer is whether the symptoms are monocular or binocular. Even very sophisticated patients may report vision loss in one eye when in act they have a homonymous hemianopia on the side o reported monocular vision loss. Simple bedside testing with alternating eye occlusion is su cient to get an answer. Most patients will have monocular symptoms. Pain ul vision loss o ten indicates a more acute process within the orbit, intracranial space, or systemically. Orbital or optic nerve in arction in giant cell arteritis is a rare but potentially li e-threatening cause o severe, unilateral vision loss. Timing is the next crucial actor to determine. Vision loss may be discovered suddenly but be subacute in its true progression; the existence o an intercurrent acute illness may prompt attention to other organ systems as well. Finally, vision loss may be transient or xed, and the di erential diagnosis may be altered signi cantly (Table 83-2). Bedside visual acuity is 20/20 OD, 20/70 OS. It does not improve with use o a pinhole. There is no relative a erent pupillary de ect, and the undi are di cult to see without dilation. Upon dilation, the consultant reports that the le t retina has hemorrhages and lipid deposition superiorly, matching an in erior de ect on perimetry (Figure 83 6). Fluorescein angiography con rms a branch retinal vein occlusion. CBC and coagulation panel are unremarkable, and a TTE/TEE are also ound to be normal. Carotid duplex scans show no hemodynamic abnormalities. The patient is scheduled or outpatient ophthalmology ollow-up in 30 days to screen or possible retinal neovascularization and resolution o macular edema. He is advised to maintain good glycemic and blood pressure control as an outpatient.

Acute vision loss rom retinal or optic nerve disease can be precipitated by hemodynamic shi ts in acutely ill patients or rom adverse e ects (hypotension, direct toxicity) o new medications. A thorough review o the patient’s medical risk actors or vision loss

TABLE 83-2 Causes of Vision Loss in Hospitalized Patients Cataract Glaucoma Macular degeneration Diabetic retinopathy Nonarteritic ischemic optic neuropathy Arteritic ischemic optic neuropathy Optic chiasm/ postchiasmal disease

Time o Onset Gradual Gradual

Severity Usually mild or moderate Severe when noticed by patient O ten severe

Unilateral vs Bilateral Bilateral >> unilateral Bilateral >> unilateral

Treatment Observation, re raction, surgery Medication vs surgery

Bilateral >> unilateral

Intravitreal medication, laser therapy

Moderate to severe

Unilateral > bilateral

Sudden

Moderate to severe

Unilateral >> bilateral

Laser therapy, intravitreal medication Usually none

Sudden

Severe

Unilateral >> bilateral

Sudden > gradual

Moderate to severe

Bilateral

Gradual (dry) Rapid (wet) Gradual

Immediate systemic corticosteroid therapy Varies by underlying cause

Table 83-2 is meant to be representative and is not exhaustive. A comprehensive ophthalmology text should be consulted i necessary.

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Figure 83 6 Visual ield testing showing loss o the in erior ield o vision in a patient with superior branch retinal vein occlusion and retinal ischemia. The ield de ect respects the horizontal meridian, consistent with the distribution o the retinal vascular supply.

C H A P T E R 8 3 D i s o r d e r s o t h e E y e

is required so that no possibilities are overlooked. The acute treatment o these patients addresses the underlying hemodynamic or coagulation disorders that may be present and the systemic illness that may have precipitated the visual loss event. Care ul ophthalmologic ollow-up is essential, especially in cases o central retinal vein occlusion (CRVO), in which there is a high risk o later retinal neovascularization and development o severe glaucoma. I giant cell arteritis is suspected, then corticosteroids (pre erably intravenous) should be started immediately. Waiting or an ophthalmology consultation and/or temporal artery biopsy is not necessary and may be harm ul since it might delay treatment o a vision-threatening condition. While consultation and biopsy are necessary to con rm the diagnosis, they can be done a ter treatment begins and the patient is being protected rom urther events. In the pregnant or immediate postpartum patient, hypertensive retinopathy with or without papilledema may occur at blood pressures below levels usually associated with malignant hypertension. Central vision loss is unusual except in severe or advanced disease; its presence should alert the clinician that urgent intervention is required to avoid permanent vision loss. Subtle optic disc swelling or hemorrhage may be dif cult to appreciate with undilated undoscopy, and ophthalmologic consultation should be obtained (inpatient i vision loss is present; otherwise, outpatient evaluation is indicated). The retinal changes should improve as better blood pressure control is obtained (Figure 83-7). CONCLUSION Hospitalized patients may develop a number o ocular disorders that will be brought to the attention o the treating physician. In many

Figure 83 7 Frisen Papilledema Scale, Grades 0-5. 585

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cases, the problems are simple and sel -limited, especially when the patient’s visual unction is not impaired. Most o these issues are best managed in the outpatient setting, where the patient can see his/her general ophthalmologist. In more complex or concerning cases in which central or peripheral visual eld loss is seen, or the patient reports severe pain, a basic bedside eye exam with attention to visual acuity (“the vital sign o the eye”), pupillary reaction, conrontational elds, and ocular motility will, along with basic inspection o the eye and adnexa, provide the ophthalmic consultant with invaluable in ormation, allowing him or her to provide optimal care to the patient.

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Dayan M, Turner B, McGhee C. Acute angle closure glaucoma masquerading as systemic illness. BMJ. 1996;313(7054):413-415.

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Kerr NM, Chew SS, Danesh-Meyer HV. Non-arteritic anterior ischaemic optic neuropathy: a review and update. J Clin Neurosci. 2009;16(8):994-1000. Prisco D, Marcucci R. Retinal vein thrombosis: risk actors, pathogenesis and therapeutic approach. Pathophysiol Haemost Thromb. 2002;32(5-6):308-311. Sanders S, Kawasaki A, Purvin VA. Patterns o extraocular muscle weakness in vasculopathic pupil-sparing, incomplete third nerve palsy. J Neuroophthalmol. 2001;21(4):256-259. Wilson LA. Acute bacterial in ection o the eye: bacterial keratitis and endophthalmitis. Trans Ophthalmol Soc UK. 1986;105(1):43-60.

84

CHAP TER

Dizziness and Vertigo Joseph M. Furman, MD, PhD

INTRODUCTION Dizziness and vertigo are common complaints and encompass a myriad o symptoms that may stem rom many organ systems. A sensation o lightheadedness or aintness may relate to the presence o orthostatic hypotension, abnormalities o the cardiovascular system, altered ambulation as seen in patients with impaired vision and sensation o eet (multiple-sensory-de ect dizziness), or imbalance experienced by older patients (benign disequilibrium o aging). Many patients describe dizziness in re erence to impaired ambulation and ear o alling or when they have blurred vision or eel con used. Hyperventilation may also cause symptoms o dizziness. These symptoms may be associated with signi cant disability and possibly mortality.

PRACTICE POINT

• Key Clinical Questions 1

How do you determine whether a hospitalized patient has a benign cause o vertigo?

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How might the physical examination con irm your suspicion o a benign cause o vertigo?

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How do you treat vertigo?

A sensation o lightheadedness or aintness may relate to the presence o orthostatic hypotension, abnormalities o the cardiovascular system, hyperventilation, altered ambulation as seen in patients with impaired vision and sensation o eet (multiple-sensory-de ect dizziness), or imbalance commonly experienced by older patients (benign disequilibrium o aging).

A sensation o vertigo, which is de ned as an illusion o movement o sel or surroundings, is much more likely to be a re ection o an abnormality o the peripheral or central vestibular system. It may be physiologic, that is, occurring with seasickness or a ter spinning or pathologic o central or peripheral vestibular origin. The misuse o the term vertigo as a diagnostic term rather than as a symptom should be eschewed in avor o a recognized diagnostic entity. Simply assigning a diagnosis o vertigo could prematurely terminate the evaluation and thereby miss an opportunity or accurate diagnosis ollowed by appropriate treatment. In some cases, the term vertigo is used as shorthand or benign paroxysmal positional vertigo. Because o the high prevalence o this disorder in the outpatient setting, these patients may receive proper treatment despite sloppy documentation and ailure to convey accurate in ormation to colleagues. This chapter primarily ocuses on the symptom o vertigo in patients admitted to the hospital. Chapter 101 includes cardiac causes o presyncope. Other medical illnesses, drug toxicity, and substance abuse that may produce symptoms o dizziness and vertigo are covered elsewhere in this book. The published studies reviewing a systematic approach to the diagnosis and treatment o the symptom o vertigo relate to the outpatient or emergency room settings. Hospitalized patients are a di erent population. I symptoms o dizziness and vertigo are new experiences, the clinician should consider iatrogenic causes in addition to the usual suspects.

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PATHOPHYSIOLOGY OF THE VESTIBULAR SYSTEM

CASE 84-1

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A 75-year-old woman with diabetes and hypertension underwent a total knee replacement. On the rst postoperative day, she experienced vertigo when turning in her hospital bed. Each brie vertiginous episode was associated with mild nausea. The patient was essentially asymptomatic when sitting or lying still. She did not suf er any perioperative hypotension. Physical and neurologic examinations revealed normal ndings. What additional diagnostic testing should be considered?

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THE VESTIBULAR SYSTEM

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The vestibular system can be divided anatomically into the peripheral and central vestibular systems. The peripheral vestibular system consists o the le t and right vestibular labyrinths and the eighth cranial nerve. The central vestibular system consists o the vestibular nuclei in the medulla and caudal pons and the pathways that subserve the vestibulo-ocular re ex, vestibulo-spinal re exes, vestibular in uences on spatial orientation, and the vestibulo-autonomic pathways that are important or the nausea and occasional vomiting that accompany vestibular system disease. Each vestibular labyrinth consists o three semicircular canals, which sense angular motion and two otolithic organs, the utricle and saccule, which sense linear acceleration and orientation with respect to gravity. The vestibular labyrinth senses motion o the head. This signal is conveyed to the vestibular nuclei via the eighth nerve. At that site, vestibular signals are combined with signals rom the visual and somatosensory systems to provide the central nervous system with an accurate representation o head orientation. With this in ormation, the central nervous system can accurately control eye position and postural stability. Note that eighth nerve a erents have a nonzero tonic resting activity, which is illustrated diagrammatically in Figure 84-1. Tonic signals rom the le t labyrinth drive the eyes and the body to the right, whereas signals rom the right vestibular labyrinth drive the eyes and body to the le t. At rest, these in uences are balanced. During movement, the a erent activity rom one labyrinth increases while the a erent activity rom the opposite labyrinth decreases. This imbalance leads to movement o the eyes or the body as appropriate to maintain stable vision and upright posture.

Vestibular disorders can be either peripheral or central. Most peripheral vestibular disorders a ect only a single labyrinth. Damage to a single labyrinth causes a le t-right vestibular imbalance. This imbalance is interpreted as intense movement toward the intact labyrinth, which leads to excessive eye movement in the orm o nystagmus, gait instability, spatial disorientation, and autonomic symptoms such as nausea, vomiting, and, in some patients, changes in heart rate and blood pressure (ie, either hypotension or hypertension). The e ects o a unilateral vestibular loss are illustrated in Figure 84-2. Over time, usually in a matter o days, central vestibular circuits rebalance despite the absence o a signal rom one o the labyrinths. This process o rebalancing, known as vestibular compensation, leads to a gradual resolution o nystagmus and gait instability (see Figure 84-3). Peripheral causes o vertigo include acoustic neuroma, aminoglycoside toxicity, benign positional vertigo, cholesteatoma, herpes zoster oticus, labyrinthine concussion related to head trauma, Ménière disease, perilymph stula, otosclerosis, recurrent vestibulopathy, and vestibular neuronitis. Central causes o vertigo include brain tumors, cerebellar or brainstem stroke, multiple sclerosis, vertebrobasilar transient ischemic attacks, and migraine-related dizziness. HISTORY OF THE PATIENT WITH DIZZINESS OR VERTIGO

■ DOES THIS PATIENT HAVE VERTIGO? The history is the most critical rst step in distinguishing vertigo rom other causes o dizziness and may pinpoint the etiology o the patient’s symptoms in up to three- ourths o patients. The examiner should care ully ask the patient what is meant by these symptoms and what brings them on. Some patients may be unable to explain their symptoms at all and respond simply that “I’m just dizzy.”Be sure to obtain an interpreter i English is not the primary language; do not make assumptions or characterize the symptoms or the patient in the interest o time. Most patients cannot adequately describe their symptoms because the sensation o dizziness and vertigo is not a normal sensation, and, unlike sensations such as vision and hearing, vestibular sensation does not have an associated vocabulary such as brightness, loudness, color, or pitch. Some patients complain

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Figure 84 1 Push-pull action of the horizontal vestibulo-ocular reflex, with no head movement, left and right vestibular influences are balanced. 588

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Figure 84 2 The reciprocal push-pull interaction of the two labyrinths is disrupted after acute peripheral labyrinthine injury. For example, following the acute loss of right unilateral peripheral vestibular function, there is a loss of resting neural activity in the right vestibular nerve and right vestibular nuclei. Because the brain normally detects differences in activity between the two vestibular nuclear complexes, even when stationary the imbalance in neural activity is interpreted as a rapid head movement, in this case to the left.

o a head sensation such as light-headedness, heavy-headedness, oggy-headedness, or presyncope. The three general types o dizziness symptoms, namely a sense o motion, imbalance, and head sensations, are not mutually exclusive. A nonspeci c complaint o a head sensation, especially light-headedness, does not exclude the possibility o a vestibular disorder whether peripheral or central, and it may result rom a metabolic derangement, drug e ect, or other organ system disease. In act, dysequilibrium, reduced cerebral perusion, and vertigo can all be associated with the symptom o dizziness with standing. Ask whether or not the dizziness is characterized by a sense o motion such as spinning, rocking or tilting, imbalance when walking, veering to the right or le t, or i the patient ears alling or has allen.

PRACTICE POINT

•

The history is the most critical rst step in distinguishing vertigo rom other causes o dizziness, and may pinpoint the etiology o the patient’s symptoms in up to three- ourths o patients. The sensation o vertigo, de ned as an illusion o movement o sel or surroundings, is much more likely to be a re ection o an abnormality o the peripheral or central vestibular system. The misuse o the term vertigo as a diagnostic term rather than as a symptom should be eschewed in avor o a recognized diagnostic entity. I the physical examination con rms the presence o benign positional vertigo and the rest o the examination is unrevealing, then no urther evaluation is necessary.

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Figure 84 3 When a peripheral vestibular injury is chronic, in this case on the right, the central nervous system is able, through vestibular compensation, to partially restore the lost resting activity within the deafferented vestibular nucleus, and thus reduce the asymmetry of neural activity between the vestibular nuclei at rest and partially restore the function of the vestibulo-ocular reflex. 589

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A ter giving the patient time to respond, sometimes asking about speci c circumstances such as when the symptoms occur, other neurologic or otologic symptoms, and whether they are recurrent may help pinpoint the diagnosis more than the description o the dizziness. Associated symptoms should be speci cally questioned: loss o consciousness, headache, tinnitus, decreased hearing, disturbance o other cranial nerves, trouble walking or controlling extremities, visual impairment, and nausea and vomiting. The examiner should determine whether the onset o dizziness or vertigo was sudden, how long it lasted, and whether worse when supine, standing, stooping, or turning the neck. Risk actors to consider include: antecedent head or neck trauma (such as hyperextension o the neck), episodes o low or high blood sugar, hypertension, prior stroke, and dehydration. Medication review is essential. Many new medications and/or toxic levels o medications due to drug-drug interactions, changes in metabolism due to renal and/or liver derangements, or incorrect prescribing can cause dizziness. Typical examples include phenytoin toxicity and reactions to some antibiotics. Because nearly all medications can potentially cause “dizziness,” clinicians should speci cally inquire about new medications.

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When ormulating a di erential diagnosis or a patient who presents with vertigo, consider whether the patient’s abnormality is a ecting the peripheral vestibular apparatus, the central vestibular system, or both and the nature o the disease process (eg, in ammatory, vascular, or neurochemical derangements). Note that peripheral vestibular disorders o ten are associated with otologic complaints such as hearing loss, tinnitus, or ear ullness. Central vestibular disorders are more likely to include associated neurologic symptoms such as numbness, weakness, and incoordination. A common misconception when obtaining a history rom patients with dizziness is to insist that patients with vertigo indicate whether they or the world around them appear to be moving. Although it is help ul to elicit a history o sel -motion and/or motion o the surroundings versus simply lightheadedness, making a distinction between motion o sel and motion o surround has no diagnostic utility (Table 84-1). THE PHYSICAL EXAMINATION OF PATIENTS WITH VERTIGO The medical history identi es patients who have true vertigo. These patients are most likely to have a peripheral vestibular etiology.

TABLE 84-1 Symptom Patterns of Vertigo Benign paroxysmal positional vertigo (benign positional nystagmus, cupulolithiasis): Normal hearing, intermittent episodes o vertigo with head turning, the most common cause o vertigo Vestibular neuronitis (vestibular neuritis): Normal hearing, sudden onset o severe, constant vertigo made worse by head movement that resolves over the course o days to weeks, second in requency Recurrent vestibulopathy: Normal hearing, intermittent episodes o constant vertigo lasting minutes or hours Toxins (drugs such as aminoglycosides or cis-platinum): Vertigo with or without hearing loss, bilateral labyrinthine dys unction Central causes of vertigo: Vertigo with symptoms o neurologic dys unction including weakness, impaired speech, diplopia

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Because true vertigo may be associated with other disorders, the evaluation o a patient complaining o vertigo should consist o a general physical examination, a neurologic examination, and, as appropriate, specialized bedside examination provocative tests. I the physical examination con rms the presence o benign positional vertigo and the rest o the examination is unrevealing, then no urther evaluation is necessary. Hospitalized patients may be more likely to have multi actorial causes to their symptoms due to their medications, uid and nutritional status, deconditioning, and other comorbid conditions (Table 84-2). Hospitalized patients who are hypovolemic may have one or more o the ollowing: nausea and vomiting due to vertigo, acute blood loss (surgical or medical), third spacing (severe liver disease), burns, or poor oral intake with limited uid replacement. The rst step is always to examine the patient’s vital signs. The physical examination should include checking or orthostatic blood pressure changes, examining the tympanic membranes, and per orming a cardiovascular examination along with listening or bruits. The criterion o a pulse increment o >30 beats per minute rom the supine to standing position may have limited utility in patients taking nodal blockers or with conduction system disease. Deconditioning can lead to orthostatic blood pressure changes as can autonomic nervous system dys unction and medications. Hence, clinical judgment is required to assess abnormal vital signs. The bedside neurologic examination should include per orming an eye examination, testing or hearing loss and checking other cranial nerves, assessing sensation o the eet, and an assessment o gait and station; see Chapter 104. An abnormal neurologic examination will likely localize the illness and determine the need or imaging.

■ SPONTANEOUS NYSTAGMUS Vertical nystagmus is a central vestibular sign that usually warrants MRI speci cally o the vestibular nuclei or o the cerebellar vermis. A unidirectional horizontal nystagmus that includes a slight torsional component is more likely caused by a peripheral abnormality. Upbeating nystagmus seen only on upward gaze is usually a benign nding akin to bidirectional horizontal gaze-evoked nystagmus. I the patient does not have spontaneous nystagmus, the examiner should per orm a provocative maneuver to test or positional nystagmus. Head impulse test To per orm the head-impulse test, the patient’s head is abruptly rotated to the right or le t while the patient attempts to xate on a distant stationary object. The examiner looks or a small rapid eye movement opposite to the direction o head movement that signies an inadequate vestibulo-ocular re ex resulting rom a disorder o the labyrinth toward which the head has been moved. Per orming this test can be dif cult in patients with an acute vestibular imbalance. Dix Hallpike maneuver To per orm the Dix-Hallpike maneuver, the examiner stands at the patient’s side and rotates the patient’s head 45° to the nearside to align the ipsilateral posterior semicircular canal with the sagittal plane o the body. The patient is instructed to keep his or her eyes open, especially i he or she experiences vertigo. The examiner then moves the patient, whose eyes are open, rom the seated to the supine ear-down position and then extends the patient’s neck slightly so that the chin is pointed slightly upward. The latency, duration, and direction o nystagmus, i present, and the latency and duration o vertigo, i present, should be noted. A positive test

produces a paroxysmal upbeating-torsional nystagmus. The examiner observes the patient’s eyes or the characteristic nystagmus that generally lasts or the duration o the patient’s vertigo.

COMMON VESTIBULAR DISORDERS IN THE HOSPITAL Common vestibular disorders that may lead to a hospital admission or that may present once a patient has been admitted or an unrelated ailment involve peripheral disorders, including vestibular neuritis, benign paroxysmal positional vertigo, and Ménière disease, and central disorders, including vestibular migraine, medication-induced dizziness and vertigo, and posterior ossa stroke. Note that patients admitted ollowing trauma may experience dizziness or vertigo on either a peripheral or central basis and that some psychiatric illnesses, notably panic disorder, may include dizziness.

A P T E R 8 4 D i z z i n e s s a n d V e r t i g o

Does this dizzy patient have vertigo? • True vertigo accounts or roughly hal o the causes o dizziness. • Sometimes asking about speci ic circumstances such as when the symptoms occur, other neurologic or otologic symptoms, and whether symptoms are recurrent may help pinpoint the diagnosis more than the description o the dizziness. Ask the ollowing questions: • Are the symptoms characterized by a sense o motion such as spinning, rocking, or tilting? • Is there a sense o imbalance when walking, veering to the right or le t, or concern about alling? I so, inquire whether the patient does not have symptoms o dizziness when sitting or lying down. Dysequilibrium accounts or roughly 3% o causes o dizziness. Does this patient have a benign cause o vertigo? • Forty percent o dizzy patients will have peripheral vestibular disorders a ecting the inner ear and cranial nerve VIII. • Benign paroxysmal positional vertigo and vestibular neuronitis are most requent diagnoses. Inquire about associated hearing loss. • For patients without associated hearing loss, the likelihood o a cerebello-pontine mass as the cause o vertigo is low (probability 1 × 10–4). Inquire about whether the vertigo is episodic or persistent. • No hearing loss and episodic, brie , intense vertigo is likely benign paroxysmal positional vertigo. • No hearing loss and persistent vertigo lasting hours to days with nausea is likely vestibular neuronitis. Inquire about associated otologic complaints. • Peripheral vestibular disorders are o ten associated with otologic complaints such as hearing loss, tinnitus, or ear ullness. • Hearing loss and episodic vertigo lasting hours with tinnitus and a sensation o ear ullness is most consistent with Ménière disease. • Hearing loss and severe persistent vertigo lasting hours to days with nausea is most consistent with labyrinthitis. Does this patient have a central cause o vertigo? • Roughly 10% o all dizziness may be central in origin. Inquire about associated neurologic complaints. • Central vestibular disorders are more likely to be associated with numbness, weakness, and incoordination. Inquire about antecedent trauma and other risk actors. Review medication list. Is this patient orthostatic? Does this patient have an abnormal neurologic examination? Does this patient have an abnormal ear examination? • Ear drainage is seen as a complication o chronic otitis media along with hearing loss and vertigo (cholesteatoma). • Ramsay Hunt syndrome may be identi ied by the presence o vesicles along with hearing loss and acial palsy. Does this patient have spontaneous nystagmus? • Spontaneous horizontal nystagmus with or without torsional nystagmus is usually seen in patients with vestibular neuronitis or in other peripheral disorders. • Vertical nystagmus is a central vestibular sign. • Upbeating nystagmus only on upward gaze and bidirectional horizontal gaze-evoked nystagmus are usually benign indings. • Absence o nystagmus during vertigo may suggest psychogenic vertigo. Does this patient have positional nystagmus that reproduces the patient’s symptoms?

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TABLE 84-2 The Clinical History and Physical Examination

■ BENIGN PAROXYSMAL POSITIONAL VERTIGO Benign paroxysmal positional vertigo (BPPV) represents a very common vestibular disorder in the outpatient and emergency room setting. BPPV may be encountered in the hospital setting, especially in patients who have undergone a surgical procedure or who require prolonged bed rest. BPPVis characterized by brie periods, generally 10 to 20 seconds, o intense rotational vertigo that may or may not be associated with nausea. Aside rom attacks o positional vertigo, patients with BPPVare o ten asymptomatic. A de nitive diagnosis o benign paroxysmal positional vertigo can be made at the bedside using the Dix-Hallpike maneuver. The nystagmus may be complex with a mixture o both upbeating and torsional (rotary) eye movement. Physical examination will be normal otherwise. Treatment or benign paroxysmal positional vertigo consists o a particle repositioning maneuver to relocate otolithic debris rom 591

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the posterior semicircular channel to the vestibule. Patients may be re erred to a physical therapist or treatment or to the ollowing website regarding the Epley maneuver or instruction in how to per orm these exercises: www.charite.de/ch/neuro/vertigo.html. Patients with chronic vertigo o vestibular origin may bene t rom a vestibular rehabilitation program designed to acilitate central compensation.

■ VESTIBULAR NEURITIS

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Vestibular neuritis generally presents with the acute or subacute onset o severe vertigo, nausea, vomiting, and disequilibrium sometimes as the sequelae o a u-like illness or an a ebrile viral illness. Symptoms are present at rest and are exacerbated by any head movement. Certain head positions may exacerbate or reduce symptoms. Severe symptoms usually last or 1 to 3 days during which acute management is required. Then, symptoms gradually resolve over a period o days or weeks. Physical examination generally reveals a unidirectional horizontal nystagmus that increases when the patient gazes in the direction o the quick component o the vestibular nystagmus. Gait instability is the rule. Note, however, that patients with vestibular neuritis are able to ambulate although they may require assistance. The headimpulse test is generally abnormal in patients with vestibular neuritis. Imaging in patients with vestibular neuritis is normal and usually not indicated. I there was something clinically that did not quite t with this diagnosis and generates some concern on the physician’s part, a de nitive diagnosis o vestibular neuritis can be established by caloric testing in the vestibular laboratory indicating a markedly reduced or absent caloric response unilaterally. It is the standard o practice to treat with corticosteroids although their bene t has not been consistently shown. Antiviral agents have not been shown to be e ective. Supportive measures may include vestibular suppressants such as meclizine, tranquilizers, and bedrest or a ew days.

■ MÉNIÈRE DISEASE Ménière disease is a term that should be reserved or patients who su er rom presumed endolymphatic hydrops, a pathophysiology that produces the triad o vertigo, unilateral hearing loss, and unilateral tinnitus. That is, the term Meniere disease should be reserved or the characteristic syndrome and should not be used to describe patients with presumed peripheral vestibular disease o uncertain etiology. These symptoms are requently associated with unilateral ear ullness. Symptoms generally last rom several minutes to several hours and occur in episodes; patients are usually asymptomatic between episodes. During episodes, patients may experience nausea, vomiting, and severe gait instability. They would be expected to exhibit a marked horizontal-torsional nystagmus independent o head position, worse with loss o visual xation. Between episodes, patients may mani est unilateral low- requency sensorineural hearing loss, which can be discovered using tuning orks and con rmed de nitively with audiometry. Balance laboratory testing o ten reveals a reduced vestibular responsiveness on the same side as the patient’s tinnitus and hearing loss. Treatment or Ménière disease consists o a reduction o dietary intake o sodium ( leg • ACA—leg > arm or ace

Posterior circulation • Motor dys unction o ipsilateral ace and/or contralateral extremity • Loss o vision o one or both eyes, homonymous visual elds • Sensory de cit o ipsilateral ace and/or contralateral extremity • Typical associated symptoms (not diagnostic in isolation) • Ataxia • Vertigo • Diplopia • Dysphagia • Dysarthria

Cortical signs include aphasia, visual eld de ects, monoparesis (clumsy, weak, or accid), hemineglect, cortical sensory loss (numbness, paresthesias), and abulia.

■ DOES THE PATIENT HAVE SIGNS OF AN UNDERLYING SYSTEMIC DISORDER? A general physical examination should search or the source o any ever, with particular attention to the ears, sinuses, respiratory system, and skin due to the association with meningitis. Any in ection may cause a toxic vascular headache characterized as bilateral throbbing headaches increased by exertion, bending, and straining or may trigger migrainous attacks. Like toxic vascular headache, bacterial, viral, ungal, or protozoal systemic in ections may cause meningeal irritation. A general physical examination may uncover a new diagnosis o cancer or evidence o metastatic disease. For example, approximately 50% o patients with meningeal carcinomatosis may have no history o systemic cancer. Patients with known cancer may develop headaches secondary to parenchymal or skull tumor metastases, carcinomatous meningitis, or intracranial venous thrombosis; however, they are more likely to have headaches rom primary causes (migraine or tension headaches) or rom ever and sepsis or rom drug therapy. Because o the potentially subtle ndings, new-onset headaches in older patients and headaches that ail to meet diagnostic criteria or primary unctional headaches should prompt neuroimaging (see Tables 89-1, 89-2, and 89-3 or the diagnostic criteria by the International Headache Society). Patients with rheumatologic disorders may have a number o di erent mechanisms or headaches, including recurrent headaches similar to migraine or chronic headaches due to vasculitis, pseudotumor cerebri, or aseptic meningitis. The signs and symptoms o cerebral vasculitis include multi ocal neurologic de cits and headache, o ten associated with systemic in ammation and ever. Granulomata rom Wegener disease, lymphomatoid granulomatosis, and sarcoidosis may in ltrate the meninges and produce headache and multiple cranial nerve de cits. Arthritis o the cervical spine may lead to neck sti ness and occipital headaches.

CASE 89-1 (continued NEUROLOGY CONSULTATION Almost certainly too much medication has caused a syndrome o chronic daily headache superimposed on a history o migraine. The best course o action would be or her to consult a headache

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FOLLOW-UP Instead, the patient consulted a pain clinic, which continued her narcotics and added a number o new medications. She continues to periodically visit emergency departments or pain relie .

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Extra-axial processes (outside o brain tissue) commonly cause raised intracranial pressure and may cause the ollowing signs to be present: evidence o raised intracranial pressure (Cushing re ex), ptosis o one eyelid (aneurysmal compression o the ipsilateral third cranial nerve), dilated nonreactive pupil (constriction controlled by ipsilateral third cranial nerve), impaired adduction and vertical movement o one eye (complete third cranial nerve compression), impaired lateral rectus muscle unction (stretching o sixth cranial nerve rom increased intracranial pressure), subhyaloid hemorrhage on retinal examination.

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expert, to help her get on a program that would allow her to taper alprazolam and hydrocodone with the goal o discontinuation and start a more rational, abortive treatment program or her headaches. The general rule is that oral medications do not help much during migraine because o atony o the stomach. Subcutaneous sumatriptan has helped her but is very expensive. It may be better to use rectal indomethacin at the rst sign o the headaches. Cyproheptadine, a mild antiserotonin drug, may cause some sedation, which in her case may be use ul since sleep and rest make the headaches better.

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I a patient has ocal neurologic signs, proceed with neuroimaging and consider imaging o the large vessels at the same time, especially i the patient has signs and symptoms along a vascular territory. With CNS mass lesions, ocal neurological de cits are usually present, although not invariably, and are o ten extremely subtle.

CONCLUSION The history and physical examination are the most important parts o the evaluation o headache at the bedside. Headache symptoms o concern include sudden rapid onset, occipitonuchal radiation, or association with ocal neurologic symptoms or altered mental status. Patient-speci c risk actors include older age, coexistent malignancy, in ectious disease, coagulopathy, or underlying immunosuppression. Precipitating actors o concern include onset during exertion or antecedent head or neck trauma. Physical examination ndings o concern include toxic appearance, ever, meningismus, papilledema, altered mental status, and ocal neurologic signs. Un ortunately, it can sometimes be dif cult to di erentiate each orm o headache type rom another, and the neurologic examination may be normal. This is why imaging is so o ten needed.

SUGGESTED READINGS Attia J, Hatala R, Cook DJ, Wong JG. In: Simel DL, Rennie D, eds. The Rational Clinical Examination. Vol. 400. New York: McGraw-Hill; 2009;400:175-181. Peter J. Goadsby, Richard B. Lipton, Michel D. Ferrari, et al. Migraine—the current understanding and treatment. N Engl J Med. 2002;346:257-270. Rasmussen BK. Epidemiology o 1995;15(1):45-68.

headache. Cephalalgia.

Samuels MA, ed. Hospitalist Neurology. Waltham, MA: Butterworth/ Heinemann; 1999. Sapira JD. The Art and Science of Bedside Diagnosis. Baltimore, MD: Urban &Schwarzenberg; 1990:469-470. Stephen D. Silberstein, Richard B. Lipton, Martin Sliwinski, et al. Classi cation o daily and near-daily headaches. Neurology. 1996;47:871-875. Sun-Edelstein C, Bigal ME, Rapoport AM, et al. Chronic migraine and medication overuse headache: clari ying the current International Headache Society classi cation criteria. Cephalalgia. 2009;29:445.

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90

CHAP TER

Hemoptysis Christopher Knudson, MD Sukit Chaiyachati, MD Alvaro Velasquez, MD

Key Clinical Questions 1

What is the initial approach in a evaluating a patient with suspected hemoptysis?

2

What are the causes o hemoptysis, and what clinical eatures can suggest the mechanism o hemoptysis?

3

What are the diagnostic tests that should be per ormed or a patient with hemoptysis?

4

What are treatment modalities or hemoptysis, and when is each appropriate?

DEFINITION Hemoptysis is coughing or spitting up blood or blood mixed with phlegm as a result o bleeding in the lower respiratory tract. The lower respiratory tract is de ned as any part o the respiratory system that is below the vocal cords or glottis. This includes the trachea, bronchi, and pulmonary parenchyma. This de nition is important in that blood that is generated rom other sources has a very di erent evaluation, triage and treatment. ANATOMY OF HEMOPTYSIS Hemoptysis may range rom large amounts o rank blood to light streaks o blood in the sputum, which suggests that hemoptysis has diverse etiologies and pathology. Bleeding rom the lower respiratory tract occurs rom one o two sources: either the high-pressure systemic arterial blood supply or the lower pressure pulmonary arteries and their branches. The lower respiratory tract blood supply starts proximally with the in erior thyroid arteries supplying the upper trachea. Next, the bronchial arteries, originating rom the aorta at the level o T3 to T8, travel along the tracheobronchial tree with small penetrating arteries eeding the lower trachea and bronchi. The bronchial arteries end by anastomosing with branches o the pulmonary arteries, together orming the capillary bed around the alveoli. The pulmonary arteries travel alongside the bronchial arteries on the tracheobronchial tree, but only per orm oxygen exchange once at the alveoli. The signi cance o these anatomical considerations is that massive hemoptysis (de ned below) is more likely coming rom the systemic arteries, and the volume o blood may help elucidate the origin o the bleeding. Ninety percent o cases o massive hemoptysis are rom bronchial arteries. The remaining 5% o cases are rom the pulmonary arteries and 5% rom other arteries. It is also important to realize that bronchial, but not pulmonary arteries proli erate in the setting o in ammation. They can enlarge, become tortuous, and create pathologic high-pressure anastomosis with nearby pulmonary arteries. These abnormal vessels are highly prone to bleeding, and explain (in part) the hemoptysis encountered with chronic in ammatory disease (eg, cystic brosis, bronchiectasis), and acilitate our understanding o recurrent bleeding in these disorders. ETIOLOGY OF SUSPECTED HEMOPTYSIS There are many causes o hemoptysis, with some o the more common listed in Table 90-1. The di erential diagnosis o hemoptysis depends primarily on the patient population. In the so-called developed world, the most common causes encountered are bronchitis, bronchogenic carcinoma, bronchiectasis, pneumonia, and tuberculosis. A recent review ound that pulmonary embolism is also a common cause o hemoptysis. In contrast, developing countries encounter active in ection or sequelae rom in ection as more common causes. Bronchitis, pneumonia, mycobacterial (eg, tuberculosis) and parasitic (eg, paragonimiasis) in ections as well as mitral valve disorders rom rheumatic ever, and bronchiectasis are generally seen most requently. INITIAL APPROACH TO A PATIENT WITH SUSPECTED HEMOPTYSIS The rst step during the evaluation o hemoptysis is to ensure that there is a patent airway, good gas exchange, and hemodynamic stability. Signs o respiratory or hemodynamic compromise such

636

H A P T E R 9 0 H e m o p t y s i

Rheumatologic disorders and vasculitis Amyloid Antiglomerular basement membrane disease (Goodpasture’s syndrome) Behçet’s disease Genetic de ect o collagen (Ehlers-Danlos vascular type) Granulomatosis with polyangiitis (Wegener’s) Systemic lupus erythematosus Trauma and iatrogenic Bronchoscopy with brushing, biopsy or needle aspiration Interventional pulmonology procedures (dilation, metallic stent placement, high-dose brachytherapy) Pulmonary artery catheter-induced vascular injury Tracheal tube erosion into innominate artery Transtracheal procedure Blunt chest trauma Penetrating chest trauma Drugs and toxins Anticoagulants, antiplatelet agents Bevacizumab Cocaine Penicillamine Solvents Trimellitic anhydride Miscellaneous Endometriosis o lung Lymphangioleiomatosis Broncholithiasis Cryptogenic Foreign body aspiration Lung transplantation

s

Cardiac and pulmonary vascular Airway-vascular istula Aneurysm: Bronchial artery Pulmonary artery (Rasmussen aneurysm, mycotic, arteritis) Arteriovenous mal ormations Congenital cardiac or pulmonary vascular mal ormations Heart ailure Mitral stenosis Pulmonary embolism, in arct Pulmonary hypertension Hematological Coagulopathy (congenital, acquired or iatrogenic) Platelet disorders (platelet dys unction, thrombocytopenia, von Willebrand Disease) Infectious Bacterial endocarditis with septic emboli Mycetoma* and other ungal in ections Mycobacteria (tuberculosis* and nontuberculosis) Necrotizing pneumonia* and lung abscess (Klebsiella pneumoniae, Pseudomonas aeruginosa, Staphylococcus aureus, Streptococcus pneumoniae, other Streptococcus spp. and Actinomyces spp.) Parasitic (paragonimiasis, hydatid cyst) Viral (Herpes simplex) Neoplastic Bronchogenic carcinoma* Endobronchial tumors (carcinoid, adenoid cystic carcinoma) Metastatic cancer to lungs Sarcoma Pulmonary Bronchiectasis* (including cystic ibrosis) Bronchitis Alveolar hemorrhage and underlying causes

C

TABLE 90-1 Causes of Hemoptysis

*The most common underlying causes o massive hemoptysis.

as dyspnea, hypoxemia or hypotension may require intubation, and at the very least monitoring in a setting where this could be per ormed quickly i deterioration occurs. I possible during intubation, bronchoscopy should be per ormed concurrently or soon a ter to attempt to localize and—i possible—suppress bleeding or clear areas o bleeding that may compromise oxygenation. Supplemental oxygen should be given as needed. Hemodynamics should be monitored at this time, with immediate intravenous (IV) access obtained and IV uids or blood products administered as appropriate. As early as possible in treating a patient with hemoptysis, positioning the patient is important. Laying the patient in the lateral decubitus position, keeping the suspected side o bleeding dependent, will theoretically prevent blood rom spilling over to the una ected lung and preventing aspiration. It may be dif cult to determine on initial exam, but some clues may be discom ort on one side o the chest, ocal crackles, or wheezes on exam. Initial radiologic studies are o ten necessary, and a rapid bedside chest radiograph may be help ul. With heavy bleeding patients sometimes cannot tolerate lying in the lateral decubitus position, and intubation and sedation may be necessary. The next triage step is to determine the extent o bleeding. Traditionally, hemoptysis has been regarded as either massive or nonmassive, but there is no clear de nition o massive hemoptysis. Di erent sources de ne anywhere rom 100 to 1000 mL

o blood over 24 hours, with some de nitions suggesting more than 100 mL/h. More important are the clinical implications o hemoptysis, and this so-called magnitude-o -e ect de nition includes eatures such as requiring trans usion, intubation, aspiration, airway obstruction or hypoxemia. We consider a signi cant magnitude o e ect rom hemoptysis as massive hemoptysis, particularly when employing the “Approach to the Patient with Hemoptysis” algorithm Figure 90-1. Massive hemoptysis is a li e-threatening event with a mortality rate ranging rom 0% to 38%, and these patients should be monitored in an intensive care unit. Calling all consultants (pulmonary, interventional radiology, and cardiothoracic surgery services) immediately is important, as rapid intervention may be required. By doing so, i urgent intervention is needed, they will be aware o the case and can respond more quickly to an emergency. BEDSIDE EVALUATION OF HEMOPTYSIS The bedside evaluation is o ten per ormed concurrently with the initial triage and should be per ormed rapidly in the setting o severe bleeding. A common clinical dif culty is determining i the patient has hemoptysis or pseudohemoptysis. Pseudohemoptysis is bleeding that initially seems to be hemoptysis but is not rom the lower respiratory tract. Hematemesis, or bleeding rom the upper 637

Initial Triag e

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CXR cle a r AND ble e ding 180 mm Hg or hypertensive patients. (The higher threshold in hypertensive patients is due to vascular hypertrophy and other morphologic changes rom chronic elevations in blood pressure.) I the upper limit o autoregulation is surpassed, endothelial dys unction and damage may occur, the blood-brain barrier may break down, and cerebral edema and microhemorrhages may develop, giving rise to hypertensive encephalopathy.

The lower limit o CBF autoregulation also di ers between hypertensive and normotensive patients. Hypertensive patients may show signs or symptoms o cerebral hypoxemia, including loss o consciousness, coma, or seizures, at MAP levels o 50 ± 5 mm Hg and below, whereas normotensive patients will show these symptoms at a MAP o 40 ± 5 mm Hg and below. This has important implications or the management o hypertensive emergencies: too rapid lowering o blood pressure in these patients poses a risk o signi cant cerebral hypoper usion.

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Figure 91 1 Autoregulation of cerebral blood flow in response to changing mean arterial pressure in normotensive patient. (Data rom Strandgaard S, Olesen J, Skinhoj E, et al. Br Med J. 1973;1(5852):507-510.) 642

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Myocardial ischemia is common, because o high myocardial oxygen demand, high-end diastolic pressures, endothelial damage, and previous myocardial hypertrophy, in patients with underlying essential hypertension. Congestive heart ailure and pulmonary edema are common. Aortic dissection is a dreaded complication, and should be suspected in those with sudden tearing or ripping chest pain radiating into the back, discordant upper-extremity pulses, and new diastolic murmurs. It should be borne in mind that neurologic symptoms in hypertensive crises may also be caused by aortic dissection disrupting the cerebral circulation.

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presence o compatible signs and symptoms, as described in Chapter 244. Care ul examination o the patient is required in all cases. In the hospital, hypertensive crises may develop a ter surgeries. Postoperative hypertension is arbitrarily de ned as a systolic blood pressure ≥190 mm Hg or a diastolic blood pressure ≥100 mm Hg on two consecutive readings ollowing surgery. More than 50% o patients have a history o hypertension prior to surgery. Postoperative hypertension is most common a ter cardiac surgery, major vascular surgery (eg, carotid and aortic procedures), head and neck surgery, neurosurgery, trauma, and organ transplantation. Increases in sympathetic tone and vascular resistance are thought to underlie the condition.

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Figure 91 2 Autoregulation of cerebral blood flow in response to changing mean arterial pressure in hypertensive patient. (Data rom Strandgaard S, Olesen J, Skinhoj E, et al. Br Med J. 1973;1(5852):507-510.)

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■ RETINOPATHY CLINICAL MANIFESTATIONS Clinical characteristics o the hypertensive crisis are summarized in Table 91-2. End-organ damage in hypertensive emergencies is summarized in Table 91-3, and discussed later in this chapter.

■ NEUROLOGIC The central nervous system is the organ system most o ten involved in hypertensive emergency. Clinical events may include stroke, hypertensive encephalopathy, intracranial hemorrhage, and subarachnoid hemorrhage. Cerebral edema o ten develops, particularly in the white matter o the parietooccipital regions, leading to the posterior reversible encephalopathy syndrome (PRES) (Figure 91-3). Although patients with this syndrome may develop severe symptoms, including headache, nausea, delirium, visual disturbances, and ocal neurologic ndings, as the name suggests, many patients recover well as the cerebral edema resolves. The reason or the parietooccipital predominance is unknown, but may involve a relative paucity o sympathetic innervation in these regions.

Visual disturbances in hypertensive crisis may be due to hypertensive encephalopathy and the posterior PRES, but they may also be due to malignant hypertensive retinopathy, characterized by swelling o the optic disc, retinal hemorrhages, and so t exudates (cotton-wool spots).

■ RENAL The kidney, like the brain, has a capacity to autoregulate its blood supply, but in the setting o a hypertensive crisis, this ability may be overwhelmed and a vicious cycle o kidney damage may ensue, characterized by vascular damage, endothelial dys unction, brinoid necrosis, in ammation, and ischemic injury. DIAGNOSIS OF HYPERTENSIVE URGENCIES AND EMERGENCIES The initial assessment should include a thorough medical history, including the duration and severity o hypertension, comorbid cardiovascular and renal disease, all current prescription and

TABLE 91-2 Clinical Characteristics of the Hypertensive Emergency Blood Pressure (mm Hg) Not needed or diagnosis but usually ≥180/120 mm Hg

Neurologic Status Cardiac Findings Headache, con usion, Prominent apical somnolence, stupor, visual pulsation, cardiac loss, seizures, ocal neurologic enlargement, de icits, coma congestive heart ailure

Funduscopic Findings Hemorrhages, exudates, papilledema

Gastrointestinal Renal Symptoms Symptoms Azotemia, Nausea, vomiting proteinuria, oliguria

Data rom Vidt DG. Hypertensive crises: emergencies and urgencies. J Clin Hypertens. 2004;6:520-525; Chobanian AV, Bakris GL, Black HR, et al. Seventh Report o the Joint National Committee on Prevention, Detection, Evaluation, and Treatment o High Blood Pressure. JAMA. 2003;289:2560-2572.

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TABLE 91-3 Examples of Hypertensive Emergencies

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Acute aortic dissection Acute ischemic or hemorrhagic stroke Subarachnoid hemorrhage Hypertensive encephalopathy Acute myocardial ischemia/in arction Acute heart ailure β-Blocker or clonidine withdrawal Catecholamine excess states Cocaine, phencyclidine hydrochloride use Eclampsia Head trauma Hemorrhage Pheochromocytoma crisis

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Data rom Hebert C, Vidt D. Hypertensive crises. Primary Care: Clin. Office Pract. 2008;35:475-487.

The review o systems should ocus on symptoms that might indicate end-organ damage rom hypertension, such as chest pain, shortness o breath, severe headache, changes in vision, dizziness, altered mental status or somnolence, oliguria, or anuria. On examination, the rst step in diagnosing a hypertensive crisis is accurate blood pressure measurement. This should be repeated at least twice, taking precautions to properly position the patient and use an adequately sized cu . Blood pressure should be checked in both arms and in the lower limbs. A blood pressure di erence o more than 20 mm Hg between arms suggests aortic dissection, but un ortunately is not a sensitive nding. The examiner should also ocus on detecting new end-organ damage. On unduscopic examination, chronic hypertensive patients o ten have chronic ndings, such as widening o the arterial stripe (copper-wire and silver-wire changes) and arteriovenous nicking. Greater signi cance is attached to acute changes, such as new hemorrhages, cotton-wool retinal exudates, and papilledema. Signs o heart ailure, such as elevated jugular venous pressures, S3 heart sounds, and pulmonary rales, should be sought on cardiopulmonary examination. A new diastolic heart murmur suggests aortic insuf ciency rom aortic dissection.

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TREATMENT

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nonprescription medications, and recreational drugs, especially cocaine and other stimulants. Patients should be questioned in a nonjudgmental way about adherence to antihypertensive medications and possible obstacles to adherence.

Figure 91 3 Axial FLAIR MRI showing increased signal (white) in the occipital subcortical white matter and cortex bilaterally. These findings are typical of the reversible posterior leukoencephalopathy syndrome (RPLS) in the setting of hypertensive emergency, and probably represent reversible vasogenic edema. Other causes of RPLS include preeclampsia, cancer chemotherapy, and cyclosporine, tacrolimus, and other immunosuppressive drugs. (Reproduced, with permission, rom Simon RP, Greenberg DA, Amino MJ. Clinical Neurology. 7th ed. New York, NY: McGraw-Hill, 2009. Fig. 1-10.) 644

Excessive blood pressure lowering should be avoided in most patients with hypertensive crisis, as many o them have chronic hypertension with vascular changes and are at risk or cerebral ischemia i blood pressure alls too quickly. This is especially true o older patients. An approach to triage in patients with hypertensive crisis is summarized in Table 91-4. In patients with hypertensive urgency, blood pressure lowering may usually be accomplished with oral medications over a 24- to 48-hour period. These patients do not necessarily require hospital admission. They may be observed and treated with oral agents or several hours prior to discharge with close outpatient ollow-up, assuming that their blood pressure alls into an acceptable range. However, i patients with hypertensive urgency are symptomatic or i there are concerns about adherence, it is reasonable to admit these patients. Patients with hypertensive crisis o ten bene t rom being in a quieter and less stress ul environment, i such can be provided in the inpatient setting. There are very ew randomized controlled trials o therapy in hypertensive crisis. In hypertensive urgency, a reasonable approach is to restart oral antihypertensives in patients who have been nonadherent, or to increase doses o current therapy in adherent patients. In patients not previously taking antihypertensive therapy, initial choices or drug therapy include an ACE inhibitor, β-blockers, or a calcium channel blocker. These patients are likely to require more than one agent or blood pressure control. Loop diuretics may be help ul in edematous patients. Sublingual ni edipine was once commonly used in the treatment o hypertensive crisis, but has allen out o avor because o the risks o re ex tachycardia and hypotension. This agent must be avoided in all cases o hypertensive crises. Patients with hypertensive emergencies ideally should be admitted to an intensive care unit or continuous monitoring o hemodynamics, neurologic status, urine output, and other mani estations o end-organ damage. Hypertensive emergencies are typically managed with short-acting titratable antihypertensive agents (Tab le 91-5). In the rst hour o therapy, the goal is to lower mean arterial blood pressure by no more than 15% to 20%, with a diastolic blood pressure in the range o 100 to 110 mm Hg. Blood pressure is urther reduced to 25% to 30% o the initial value within the next 4 to 8 hours. Oral antihypertensive agents should replace intravenous agents only when stable blood pressure control has been achieved, and there is no evidence o continuing end-organ damage. Sodium nitroprusside used to be the pre erred agent or hypertensive emergency, given its rapid onset o active, easy titration

H A P T E R 9 1 H y p e r t e n s i v

Arrange ollow-up within 3-7 d; i no prior evaluation, schedule appointment

Immediate admission to intensive care unit; treat to initial goal BP; additional diagnostic studies

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Observe at least 1-3 h; initiate, resume medication; increase dosage o inadequate agent

Shortness o breath, chest pain, nocturia, dysarthria, weakness, altered consciousness Encephalopathy, pulmonary edema, renal insu iciency, cerebrovascular accident, cardiac ischemia Baseline laboratory tests; intravenous line; monitor BP; may initiate parenteral therapy in emergency room

i e d E m e r g e n c i e

Fenoldopam is a selective dopamine-1 receptor antagonist and short-acting vasodilator. It seems as e ective as sodium nitroprusside in hypertensive crisis, with the advantages o improved renal per usion and promotion o diuresis, with less side e ects. Tachyphylaxis usually develops a ter 48 hours. Nitroglycerin can be used in hypertensive emergencies, although high intravenous doses o this agent are required to lower blood pressure. This drug may be especially help ul in the management o hypertension with myocardial ischemia. Headache is common with both enoldopam and nitroglycerin. Clevidipine is a short-acting dihydropyridine calcium channel blocker that selectively inhibits the in ux o extracellular calcium through the L-type channels. It has minimal e ect on myocardial contractility. Side e ects include headache, re ex tachycardia,

s

and rapid cessation o action when in usions are halted. However, sodium nitroprusside is a power ul vasodilator, and most authors caution against its use in patients with increased intracranial pressure and other conditions. Thiocyanate toxicity, mani esting as con usion and lactic acidosis, is likely with nitroprusside in usions, especially when high doses are given in the setting o renal insu ciency. For this reason, nitroprusside in usions should not continue beyond 24 hours. The author strongly recommends against the use o this agent. Other agents include labetalol (a β-1 and β-2 adrenergic blocking agent), which should be used with caution in the setting o bradycardia, atrioventricular block, heart ailure, and bronchospasm, and the dihydropiridine calcium channel blocker nicardipine, which is associated with mild re ex tachycardia, headache, and ushing.

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Data rom Vidt DG. Hypertensive crises: emergencies and urgencies. J Clin Hypertens. 2004;6:520-525.

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Therapy

Severe headache, shortness o breath Target organ damage; clinical cardiovascular disease present, stable Observe at least 3-6 h; lower blood pressure with shortacting oral agent; adjust current therapy Arrange ollow-up evaluation in less than 72 h

r

Headache, anxiety; o ten asymptomatic No target organ damage, no clinical cardiovascular disease

Hypertensive Emergency Usually >180/120

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Examination

Asymptomatic 39°C predictive o mortality in a patient with a pontine hemorrhage

+LR (95% CI) 23.7 (1.5, 371)

–LR (95% CI) 0.4 (0.2, 0.6)

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TABLE 92-5 Utility o Clinical Findings or Diagnosing Hyperthyroidism –LR (95% CI) 0.2 (0.2, 0.3) 0.7 (0.7, 0.7) 0.1 (0.1, 0.2) 0.7 (0.6, 0.7) 0.8 (0.8, 0.8) 0.3 (0.3, 0.4)

In the presence o a serotonergic agent, must meet one o the ive criteria below 1. Spontaneous clonus 2. Inducible clonus and agitation or diaphoresis 3. Ocular clonus and agitation or diaphoresis 4. Tremor and hyperre lexia 5. Hypertonic and temperature >38°C and the presence o either ocular clonus or inducible clonus

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Pulse ≥90 beats/min Skin moist and warm Enlarged thyroid Eyelid retraction Eyelid lag Fine inger tremor Wayne index ≥20 points

+LR (95% CI) 4.4 (3.8, 5.1) 6.7 (5.0, 9.1) 2.3 (2.1, 2.5) 31.5 (16.6, 59.7) 17.6 (9.2, 33.7) 11.4 (8.7, 14.8) 18.2 (2.9, 113.5)

TABLE 92-7 Hunter Serotonin Toxicity Criteria

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PRACTICE POINT Hyperre exia and ankle clonus are suggestive o serotonin syndrome in the appropriate clinical setting. Patients with neuroleptic malignant syndrome tend to have hypore exia and lead-pipe rigidity.

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Distinguishing between serotonin syndrome and neuroleptic malignant syndrome is dif cult. Typically, serotonin syndrome develops in minutes to hours a ter exposure to serotonergic agent, and NMS may occur at any time during treatment. Some have suggested that patients with NMS demonstrate higher evers and more pronounced extrapyramidal e ects, while patients with serotonin syndrome have lower evers, myoclonus, and gastrointestinal symptoms.

■ FEVER When pursuing in ectious etiologies, the physical exam should be guided by the presenting complaints but still comprehensively evaluate all organs, including the skin. The possibility o pneumonia and bacteremia should be thoroughly evaluated, as these are two o the most common diagnoses in the inpatient setting. The patient’s perception o ever, or the examiner simply detecting an abnormally warm orehead, is associated with an increasing likelihood o ever be ore a ever has been objectively detected. The patient’s perception carries a positive likelihood ratio o 2.9 (95% CI: 1.1-8.0) and the nding o a warm orehead carries a positive likelihood ratio o 2.9 (95% CI: 2.5-3.5). Physical exam ndings or maneuvers that may help in the diagnosis o bacteremia are listed in Table 92-8. The presence o hypotension is the most help ul or increasing the probability o bacteremia. Being below the age o 50 or having a temperature less than 38.5°C is the most help ul or ruling out bacteremia, assuming the patient is not HIV-positive.

TABLE 92-6 Criteria or the Diagnosis o Neuroleptic Malignant Syndrome Major Criteria or NMS Fever Muscular rigidity Elevated creatinine phosphokinase (or aldolase, creatine kinase)

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Minor Criteria or NMS Tachycardia Labile blood pressure Tachypnea Altered consciousness Sweating Leukocytosis

Physical exam ndings or maneuvers that may help with the diagnosis o pneumonia are listed in Table 92-9. The most help ul ndings are diminished breath sounds, bronchial breath sounds, egophony, cachexia, percussion dullness, and a Heckerling score o 4 or 5. The absence o any o the ndings above is not help ul or ruling out pneumonia. For diagnosing meningitis, nuchal rigidity assessment can be help ul (Table 92-10). For a ew o the nonin ectious causes o ever, there are signi cant physical exam ndings that may aid in diagnosis. Table 92-11 shows help ul ndings in the diagnosis o pulmonary embolism, such as a high probability Wells score or unilateral cal pain. A temperature greater than 38°C suggests an alternative diagnosis. The ndings help ul or detecting deep vein thrombosis are provided in Table 92-12. The most help ul ndings are a history o active cancer, asymmetric cal swelling, and high pretest probability Wells score. THE LABORATORY APPROACH

■ HYPERTHERMIA A creatine phosphokinase or aldolase evaluation should be ordered. These tests are usually highly elevated in malignant hyperthermia, NMS, or serotonin syndrome, but they may also be elevated in sympathomimetic overdose, anticholinergic overdose, and heat stroke. However, there is no diagnostic test that distinguishes between these potential causes. I in ection remains likely, an evaluation o the central nervous system (CNS) is warranted, and a diagnostic lumbar puncture should be per ormed i there are no signs o increased intracranial pressure or ocal neurologic de cits. Although not diagnostic, NMS typically presents with leukocytosis (10,000-40,000 white blood cells/µL), and low levels o serum magnesium, calcium, and iron. O ten, patients initially have metabolic alkalosis, elevated liver enzymes, and elevated lactate dehydrogenase.

TABLE 92-8 Utility o Clinical Findings or Diagnosing Bacteremia Age 50 or greater Temperature ≥38.5°C Tachycardia Respiratory rate >20 Hypotension Con usion or depressed sensorium

+LR (95% CI) 1.4 (1.2, 1.6) 1.2 (1.1, 1.3) 1.2 (1.1, 1.4) 0.9 (0.8, 1.1) 2.6 (1.6, 4.4) 1.5 (1.3, 1.8)

–LR (95% CI) 0.3 (0.1, 0.8) 0.5 (0.2, 1.0) 0.7 (0.6, 0.9) 1.2 (0.8, 1.7) 0.9 (0.9, 1.0) 0.9 (0.8, 1.0)

The history and physical exam should guide the laboratory approach based upon the pretest probability or serious in ection or underlying malignancy. I serious in ection remains likely, the laboratory approach should include a complete blood count, complete metabolic panel, blood cultures, urinalysis, and chest x-ray. A le t shi t in the white blood cell count with bandemia, toxic granulations, and Dohle bodies suggests bacteremia (Figure 92-2). A C-reactive protein level may be help ul to screen or the presence o disease in patients with low-grade or borderline ever. I there is reversal o usual peak and trough temperatures, disseminated tuberculosis (TB) and typhoid ever could be considered. Temperature-pulse dissociation with relative bradycardia may be seen with typhoid ever, brucellosis, leptospirosis, babesiosis, malaria, legionella, viral hemorrhagic evers, Gram-negative invasive rods (eg, Escherichia coli, Salmonella, Shigella), actitious ever, and some drug-induced evers. Relative bradycardia in an obscure ebrile illness in the hospital, in the absence o pneumonia, suggests a drug- ever-hypersensitivity reaction marked primarily by ever and a pulse-temperature de cit with no cutaneous mani estations. It is estimated that up to 10% o patients hospitalized in the United States have evers due to drug hypersensitivity. Fever patterns o hospitalized patients are usually o limited utility, but characteristic tertian (every third day) or quotidian (every ourth day) evers should prompt consideration o Plasmodium vivax or Plasmodium malaria, respectively. I exposure is likely, this would guide test ordering to include thick and thin blood smears. Fevers that last or 3 to 10 days ollowed by similar a ebrile periods (Pel-Ebstein evers) are seen with lymphomas, including Hodgkin lymphoma. Fevers every 21 days accompanying neutropenia are associated with a condition termed cyclic neutropenia. Additional in ormation regarding the diagnostic approach to ebrile patient is ound in Chapter 206 (Undiagnosed Fever in Hospitalized Patients).

TABLE 92-10 Utility o Nuchal Rigidity or Diagnosing Meningitis Nuchal rigidity

+LR (95% CI) 3.0 (2.1, 4.2)

–LR (95% CI) 0.1 (0, 2.0)

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TREATMENT

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■ HYPERTHERMIA ■ FEVER

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1.1 (1.1, 1.1) 0.9 (0.8, 1.0)

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0.7 (0.6, 0.9) 0.8 (0.7, 0.9) 0.9 (0.8, 1.0) 0.9 (0.9, 1.0) 0.7 (0.6, 0.8) 0.8 (0.7, 0.9) 0.8 (0.7, 0.9) 0.9 (0.8, 1.0)

–LR (95% CI) 1.1 (1.0, 1.2) 0.9 (0.8, 1.1) 0.9 (0.8, 0.9) 1.0 (0.9, 1.0)

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1.8 (1.3, 2.5) 2.2 (1.5, 3.2) 4.0 (1.7, 9.6) 1.9 (1.2, 3.0) 2.0 (1.5, 2.6) 2.0 (1.4, 2.8) 1.6 (1.4, 1.7) 3.0 (1.7, 5.2) 8.2 (5.8, 11.5)

Temperature >38°C Pulse >100/min Respiratory rate >30/min Systolic blood pressure 37.8°C Respiratory rate >28/min Heart rate >100 beats/min Percussion dullness Heckerling score, 4 or 5 indings

TABLE 92-11 Utility o Clinical Findings or Diagnosing Pulmonary Embolus

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TABLE 92-9 Utility o Clinical Findings or Diagnosing Pneumonia

Once the diagnosis o hyperthermia is established, potential o ending drugs should be discontinued. The central core temperature should be monitored continuously by rectal, esophageal, or tympanic probe. Vital signs should be closely monitored as well. Aggressive volume resuscitation is extremely important. I rhabdomyolysis is signi cant, intravenous uids are essential to avoid the risks o myoglobinuria. Active measures should be taken to lower body temperature (Table 92-13). The best method is debated, but direct application o ice packs to the groin, axilla, and neck can be used. Evaporative cooling may be used, in which the naked patient is sprayed with alcohol and water and cooled with ans. Immersion in cool water is an option but may inter ere with resuscitation and lead to complications rom vasoconstriction. Other methods include extracorporeal bypass, cooling blankets, and iced peritoneal or gastric lavage. There has been much success with the rapid in usion o 30 mL/kg o iced (4°C) normal saline to induce hypothermia in comatose survivors o cardiac arrest, and this should be considered in patients with hyperthermia. To prevent excessive cooling, these methods should be halted when core body temperature reaches 38.5°C. Dantrolene and bromocriptine are the main medications or the treatment o NMS. Intravenous clonidine, carbamazepine, amantadine, levodopa, and anticholinergic medications have been used in case reports. Treatment should continue or at least 10 days and then tapered slowly. I the insult is due to depot antipsychotics,

TABLE 92-12 Utility o Clinical Findings or Diagnosing Deep Venous Thrombosis Active cancer Recent immobilization Recent surgery Any cal or ankle swelling Asymmetric cal swelling, ≥2 cm Swelling o entire leg Super icial venous dilation Wells score, high pretest probability

+LR (95% CI) 2.9 (2.4, 3.6) 1.6 (1.3, 2.1) 1.6 (1.3, 1.9) 1.2 (1.1, 1.3) 2.1 (1.8, 2.5)

–LR (95% CI) 0.9 (0.8, 0.9) 0.9, (0.8, 0.9) 0.9 (0.9, 1.0) 0.7 (0.6, 0.8) 0.5 (0.4, 0.7)

1.5 (1.2, 1.8) 1.6 (1.4, 1.9) 5.2 (3.2, 8.5)

0.8 (0.6, 0.9) 0.9 (0.8, 0.9)

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TABLE 92-13 Additional Treatments or Speci ic Causes o Hyperthermia

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Cause o Hyperthermia 1. Malignant hyperthermia 2. Neuroleptic malignant syndrome 3. Serotonin syndrome

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6. Endocrine 7. Heat stroke 8. CNS injury/in ection

Speci ic Additional Treatments Dantrolene, hyperventilation with 100% oxygen Bromocriptine, dantrolene, muscle relaxants Serotonin antagonists, propranolol, benzodiazepines, cyproheptadine Sympatholytics, benzodiazepines Physostigmine (rarely needed), sedatives Propranolol, methimazole Supportive care Antibiotics

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Figure 92 2 Toxic granulations of a neutrophil.

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treatment should extend or a total o 2 to 3 weeks. In cases re ractory to medical treatment, electroconvulsive therapy may be used to improve ever, sweating, and delirium. Most patients with serotonin syndrome will improve within 24 hours a ter stopping the causative agents and beginning supportive therapy. Besides rapid cooling, benzodiazepines can be used to induce muscle relaxation and decrease associated anxiety. Cyproheptadine and chlorpromazine may be used to combat many o the symptoms associated with serotonin syndrome. Cyproheptadine is considered to be the rst line, as chlorpromazine can cause hypotension, which should be avoided in the setting o cardiovascular instability. Antipyretics, such as nonsteroidal anti-in ammatory drugs (NSAIDs) or acetaminophen, have no role in hyperthermia because the actions o these medications are distinct rom the underlying mechanisms o hyperthermia. Acetaminophen can hasten hepatic damage, and salicylates can worsen existing coagulopathy.

■ FEVER NSAIDs and acetaminophen are use ul or treating ever. NSAIDs decrease prostaglandin E2 through inhibition o cyclooxygenase (COX)-1 and COX-2. Acetaminophen is a poor inhibitor o COXin the periphery and is thought to work as an inhibitor o COX-3, which is located in the CNS. There is no convincing evidence that treating a ever changes time to recovery rom in ection. Preexisting cardiac,

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cerebrovascular, or pulmonary disease is aggravated by ever, and aggressive treatment should be considered. Aspirin should not be used or patients with thyrotoxic storm; it can displace thyroid hormone rom thyroid binding globulin, and thereby increase ree T4. Ultimately, the underlying cause o the ever should be targeted, whether it is in ectious, in ammatory, vascular, or autoimmune in nature.

SUGGESTED READINGS Gruber MP. Diagnosing neuroleptic malignant syndrome. Chest. 2004;125:1960-1961. Marik PE. Fever in the ICU. Chest. 2000;117:855-869. Martinez M, Devenport L, Saussy J, Martinez J. Drug-associated heat stroke. South Med J. 2002;95:799-802. McAllen K, Schwartz D. Adverse drug reactions resulting in hyperthermia in the intensive care unit. Crit Care Med. 2010;38:S244-S252. McGee SR. Evidence-Based Physical Diagnosis. 3rd ed. St. Louis, MO: Saunders Elsevier; 2012. Musselman ME, Saely S. Diagnosis and treatment o drug-induced hyperthermia. Am J Health Syst Pharm. 2013;70:34-42. Perry PJ, Wilborn CA. Serotonin syndrome vs neuroleptic malignant syndrome: a contrast o causes, diagnoses, and management. Ann Clin Psychiatry. 2012;24:155-162.

93

CHAP TER

Hypotension Danielle Jones, MD, FACP Lorenzo Di Francesco, MD, FACP, FHM

Key Clinical Questions 1

What symptoms and signs should be assessed in the initial evaluation o a patient with reported hypotension?

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What are the major categories o hypotension?

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What are the common iatrogenic complications that produce hypotension in the hospital?

INTRODUCTION Hypotension may be the presenting reason or hospital admission or it may develop during a patient’s hospitalization, sometimes as an iatrogenic complication. Out o hospital nontraumatic hypotension is associated with increased in hospital mortality. Additionally, hypotension observed in the emergency room or that develops during management o acute decompensated heart ailure, COPD and community acquired pneumonia or sepsis have all been associated with higher mortality. Because patients with hypotension may decompensate quickly, su er irreversible end-organ damage, and ultimately die, clinicians must recognize the clinical presentation o patients with li e-threatening or reversible causes o hypotension and appropriately intervene expediently. Deviations rom “normal” blood pressure must be considered in the context o the patient’s baseline blood pressure. A patient’s blood pressure normally varies depending on the time o day, even rom minute to minute, and typically decreases during sleep by 10% to 20%. Arterial monitoring has shown that the systolic and diastolic blood pressure also varies with the respiratory cycle and with each heartbeat. Although hypotension typically re ers to blood pressure lower than 90/60 mm Hg, some patients may be completely asymptomatic at such readings, whereas other patients may develop clinically important hypotensive symptoms at much higher readings. A patient with advanced cirrhosis, or example, may have a chronic stable systolic blood pressure o ~90 mm Hg that requires no intervention, whereas a severely hypertensive patient may experience a stroke, myocardial in arction, or renal insu ciency rom relative hypotension with “normal” blood pressure readings. Acute decreases in mean arterial pressure (typically >25%), such as a ter receiving a parenteral antihypertensive medication, put patients at greatest risk or acute end-organ damage and potential morbidity and mortality.

CASE 93-1 The hospital’s rapid response team (RRT) was summoned to the bedside o an 87-year-old man who had recently undergone a total hip replacement a ter sustaining a hip racture rom a mechanical all. His vital signs were notable or no discernible blood pressure, a heart rate o 110, respiratory rate o 20, O2 saturation o 95% (on 2 L via nasal cannula), and a temperature o 96° F. Telemetry review revealed sinus tachycardia. Postoperatively he had an agitated delirium, developed renal insu ciency, and became hypertensive. He had received 10 mg o intravenous (IV) hydralazine or a blood pressure o 180/100 mm Hg 30 minutes be ore the RRT call. His manual systolic blood pressure a ter placement in the Trendelenburg position was noted to be 70 mm Hg. Rapid in usion o normal saline was ordered. His usual antihypertensive medications were held, and he was trans erred to the intensive care unit (ICU). O note, the ef ects o hydralazine, a potent vasodilator, may be unpredictable when used in acutely ill patients, especially the elderly. Renal insu ciency prolongs its hal -li e. Treatment o the underlying condition that caused this patient’s hypertension (agitated delirium) is likely to be more ef ective and sa er than using antihypertensive agents to treat the elevated blood pressure directly. Importantly parenteral antihypertensive agents should only be used or patients with true hypertensive emergencies 657

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(eg, hypertensive encephalopathy, acute cardiogenic pulmonary edema, malignant hypertension o the kidney, etc) or to control blood pressure in patients unable to receive enteral antihypertensive medications in particular in the postoperative period.

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IS THE REPORTED BLOOD PRESSURE MEASUREMENT ACCURATE?

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A ter quickly ensuring that the patient is alert and responsive and that advanced cardiac li e support (ACLS) does not need to be initiated, the rst step is to determine whether the reported blood pressure reading is a valid measure o intra-arterial blood pressure; this requires assessing the blood pressure manually. Many actors may a ect the immediate accuracy o a blood pressure measurement, including the device used (cu size, leaky bulb, aulty aneroid device), the technique or bias o the examiner (positioning o patient, placement o the cu , inappropriately rapid def ation, excess bell pressure), and a noisy environment. Most errors overestimate the blood pressure, so a report o low blood pressure should alert the clinician to a possible impending emergency. In general, when assessing a hypotensive patient, the examiner should obtain a manual blood pressure reading.

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DOES THE BLOOD PRESSURE READING REFLECT CENTRAL ARTERIAL PRESSURE?

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A ter a low blood pressure is con rmed, the next step is to determine whether the blood pressure reading ref ects an acute drop in central arterial pressure. In general during initial encounters with hypotensive patients, physicians should personally record blood pressure measurements in both arms and, depending on the reason or admission and comorbidities, obtain orthostatic blood pressure readings. In an asymptomatic patient who has a history o vascular disease, a targeted vascular examination should be per ormed. Any hemodynamically signi cant vascular stenosis in the arms could result in a systolic di erence o at least 10 or 15 mm Hg. Uncommonly, patients may have bilateral stenosis in both subclavian arteries, resulting in alsely low blood pressure in both arms, but in this setting a low blood pressure reading would be unlikely to cause symptoms o decreased per usion unless accompanied by vascular disease elsewhere. I upper extremity vascular disease is suspected as the etiology or inaccurate upper extremity blood pressure readings, large thigh cu s can sometimes be used (with the patient reclined) to obtain accurate blood pressure measurements (Table 93-1).

PRACTICE POINT Postural hypotension

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Normally the diastolic pressure remains the same or rises slightly and the systolic pressure stays the same or drops slightly when a patient stands. The diastolic pressure almost never drops, and when it does, the drop is small and the systolic pressure will rise so that mean arterial pressure (MAP) = DBP + 1/3 [SBP – DBP] does not change Hypotension in the upright position compared with the recumbent position is caused by the ollowing: Volume depletion rom hemorrhage, surgery, gastrointestinal losses, adrenal insu ciency, or diuretics Autonomic dysfunction: Neurogenic actors rom some antihypertensive medications, autonomic dys unction due to diabetes mellitus, Shy-Drager syndrome, prolonged bedrest, severe heart ailure due to inability to increase cardiac output with standing

•

Failure o the heart rate to rise in response to an orthostatic drop in blood pressure suggests neurogenic actors rather than volume depletion. Exceptions include patients receiving β-blockers or nondihydropyridine calcium channel blockers (eg, diltiazem, verapamil) and patients with predominant vagal insu ciency (diabetics, postcardiac transplant). Measure blood pressure and pulse a ter the patient has rested in the supine position or 5 minutes, then standing or at least 3 minutes. Avoid measurement in the sitting position unless the patient is unable to stand due orthostatic symptoms prior to standing. Orthostasis is de ned as a all in systolic blood pressure o ≥20 mm Hg or diastolic blood pressure o >10 mm Hg. Orthostatic hypotension is de ned by systolic blood pressure 10 mm Hg) is by de nition an exaggeration o the normal inspiratory respiratory all in systolic blood pressure (normal ≤10 mm Hg). It is most commonly associated with cardiac tamponade (see Chapter 130 [Myocarditis, Pericardial Disease, and Cardiac Tamponade]) or severe obstructive lung disease, but it can also be seen in tension pneumothorax, massive pulmonary embolism, right ventricle in arction, hemorrhagic shock, large bilateral pleural e usions and in restrictive cardiomyopathy. The initial examination should include an assessment o the patient’s volume status (by estimating central venous pressure [CVP] and evaluating orthostatic blood pressures measurements), cardiac output (by examining heart and lungs), and perfusion o organs (by assessing the patient’s mental status, urine output, and the warmth over the knee caps). Skin pallor and the degree o diaphoresis should be observed, and recent administration o vasoactive medications reviewed. FRAMEWORK OF HYPOTENSION EVALUATION The clinician must evaluate the hypotensive patient at the bedside and con rm the low blood pressure through a manual measurement (ie, with an analog sphygmomanometer, and not an electronic or automatic device). Then, i the patient appears unstable, lower the head o the bed, place the patient on a bedside monitor, and evaluate or the presence o a shockable tachyarrhythmia or evidence o severe bradyarrhythmia that might require administration o atropine or pacing. I the patient is in extremis, ACLS protocols should be ollowed (see Chapter 137 [Inpatient Cardiac Arrest and Cardiopulmonary Resuscitation]). Figure 93-1 provides the initial assessment and stabilization algorithm or acute hypotension. The examiner should rapidly determine the likely mechanism o the patient’s hypotension. Most causes o hypotension will respond to aggressive f uid resuscitation; however, excessive f uid expansion may worsen right and le t ventricular ailure. Treatment o cardiogenic shock, there ore, is directed at the underlying etiology and the pathophysiology. While resuscitating a hypotensive patient, the clinician should communicate with the patient (when possible), amily members (when available), the patient’s bedside nurse and others amiliar with the patient to help identi y changes in mental status; and perorm a ocused chart review to assess recent vital signs, urine output, and risk actors or causes o hypotension. Always review the notes or the last 24 hours and the medications that have recently been

C H A P T E R 9 3 H y p o t e n s

The presentation o hypovolemic hypotension depends on the etiology, severity, and duration o the problem as well as the patient’s age and underlying medical conditions. Patients typically have abnormal vital signs (tachycardia and tachypnea) and a narrow pulse pressure in addition to low blood pressure. Symptomatic patients appear pale with f attened neck veins and cool, clammy, or mottled extremities; poor capillary re ll; diminished peripheral pulses; and altered mentation. Make note o any administrations o β-blockers and nondihydropyridine calcium channel blockers as they may mask some o the early symptoms and signs o acute blood loss and volume depletion, particularly the ref ex increase in heart rate. β-blockers can also mask other signs o increased adrenergic tone, such as diaphoresis. Hypovolemia is characterized by reduced blood volume or CVP and increased systemic vascular resistance in an e ort to maintain per usion. Acute blood loss triggers cardiovascular, respiratory, renal, hematologic, and neuroendocrine responses to increase heart rate and contractility, conserve sodium and water, control blood loss at the source o bleeding, and redistribute blood f ow to preserve vital organ unction. With progressive hemorrhage or continued volume depletion without resuscitation, cardiac output can no longer compensate, leading to arterial hypoper usion. I the examiner identi es symptoms and signs o hypovolemia, volume depletion and/or acute blood loss likely accounts or the hypotension. Volume depletion in the hospital setting may result rom decreased f uid intake or rom increased f uid losses, especially seen with vomiting, nasogastric suction, drains, diarrhea, and intentional diuresis. Increased rates o insensible losses can be dramatic when the skin is damaged (eg, burns, Stevens-Johnson syndrome) or when patients have a high ever and lose f uid via perspiration and a high respiratory rate. Hemorrhage may result rom trauma, bleeding rom the genitourinary or gastrointestinal tracts, and vascular etiologies. Hospital-acquired etiologies include trauma rom surgery or procedures and drug interactions that lead to excessive anticoagulation and spontaneous bleeding.

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WHAT ARE THE SYMPTOMS AND SIGNS OF HYPOTENSION?

■ HYPOVOLEMIC SHOCK

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The next step is to determine whether the patient is experiencing symptoms related to their hypotension. I the patient is asymptomatic, the clinician has more time to review the prior blood pressure measurements and hospital records with the goal to adjust any medications that may be contributing. Assuming a con rmed accurate low blood pressure reading, asymptomatic patients are more likely to be young and healthy, pregnant, or have systemic diseases such as severe hypothyroidism, chronic adrenal insu ciency, heart ailure, cirrhosis, or vascular disease.

administered (Table 93-2). Discontinue any medications that likely exacerbated or caused the hypotension. Order stat studies including 12-lead ECG, cardiac enzymes, complete blood count, comprehensive metabolic pro le, coagulation pro le, lactate, arterial blood gas, blood and urine cultures, and type and screen or possible blood trans usion i appropriate.

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DOES THE LOW BLOOD PRESSURE READING REFLECT THE PATIENT’S AVERAGE BLOOD PRESSURE?

PRACTICE POINT Hypovolemic shock Blood Loss (% circulating blood) Associated Signs 40% Tachycardia, pro ound hypotension, either tachypnea or irregular respirations, ↓ ↓ urine output, ↓ or absent pulses, pallor, lethargy, obtundation Death rom severe Respiratory arrest prior to circulatory arrest hemorrhage or due to atigue o respiratory muscles severe and bradycardic or asystolic rhythms or Volume depletion pulseless electrical activity (PEA)

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90-100/min and an SBP 40% o le t ventricular mass Right ventricular in arct IV luid volume load and dobutamine

Rupture o papillary muscles or the ventricular wall Acute, massive pulmonary embolism

T

Pearls and Pit alls Caution in patients with CHF who are hypotensive due to overdiuresis

E

Initial Management Aggressive IV luid resuscitation

Thrombolysis and IV luids as needed

Consider luid retention i patient does not have neck vein distension; may need pressor support in an intensive care unit setting and urgent specialty consultation Aggressive luid administration, pressors, antibiotics Stop drug, aggressive luid administration, epinephrine Fluid administration Administer IV luids and discontinue precipitants See Table 93-4 or antidotes

Paradoxical worsening o hypotension may develop i right ventricle is severely dilated and septal bowing compromises le t ventricular illing Administer IV luids care ully as excessive luid expansion may worsen right ventricular ailure Removal o even a small amount o luid (eg, 10-20 mL) by pericardiocentesis can lead to dramatic improvement

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Type o Hypotension or Shock Hypovolemic

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TABLE 93-3 Initial Management of Common Types of Hypotension

Paradoxical worsening o hypotension may develop i right ventricle is severely dilated and septal bowing compromises le t ventricular illing

Care ully review all medications, including as needed medications

TABLE 93-4 Agents Used to Reverse Medication-Induced Hypotension Hypotension-Inducing Agent Anticholinergics (eg, atropine) Benzodiazepines Beta-blockers Calcium channel blockers

Opiates

Tricyclic antidepressants

Antidote Physostigmine

Antidote Dosing 0.5-2 mg IVor IM (may repeat every 20 min until response occurs)

Flumazenil Glucagon Atropine (i bradycardia present) Calcium chloride (10%) Calcium gluconate (10%) Glucagon Nalme ene Naloxone

0.2 mg IV(may repeat) 5-10 mg IV 0.5-2 mg IV 10 mL or 1-2 g IV(may repeat to max 10-12 g) 20 mL IV 5-10 mg IV Nonopioid-dependent: 0.5-1 mg/70 kg (may repeat) Opioid-dependent: 0.10.5 mg/70 kg (may repeat) 0.4-2 mg IV(may repeat) IM and SQ available (longer onset to action) 50-100 mEq IVbolus or norepinephrine 4-8 mcg/min IVin usion

Sodium bicarbonate

Data rom Olson K. Poisoning. In: McPhee SJ, Papdakis MA, eds. Current Medical Diagnosis and Treatment 2010. New York, NY: The McGraw-Hill Companies; 2009. Chap. 38.

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SUGGESTED READINGS

Luciano GL, Brennan MJ, Rothberg MB. Postprandial hypotension. Am J Med. 2010;123(3):281.e1-281.e6.

Cook DJ, Simel DL. The rational clinical exam: does this patient have abnormal central venous pressure? JAMA. 1996;275(8):630-634.

Pickering TG, Hall JE, Appel LJ, et al. Recommendations or blood pressure measurement in humans and experimental animals. I. Blood pressure measurement in humans: a statement or pro essionals rom the Subcommittee o Pro essional and Public Education o the American Heart Association Council on High Blood Pressure Research. Circulation. 2005;111:697-716.

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Freeman MB. Neurogenic orthostatic hypotension. N Engl J Med. 2008;358:615-624.

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Jones AE, Stiell IG, Nesbitt LP, et al. Nontraumatic out-o -hospital hypotension predicts inhospital mortality. Ann Emerg Med. 2004;43:106-113.

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Levy JH. Treating shock—old drugs, new ideas. N Engl J Med. 2010;362:841-843.

664

94

CHAP TER

Hypothermia Chad S. Miller, MD, FACP, FHM Jef rey G. Wiese, MD, MHM, FACP

CASE 94-1 A 54-year-old man was brought to the hospital a ter being ound unresponsive in his apartment. His amily noted that he had been recently hospitalized or pneumonia and had been released rom the hospital 3 days earlier. The ambient temperature o the apartment was normal per the EMS report. His temperature was 32°C, his heart rate was 50 beats/min, his respiratory rate was 14 breaths/min, and his blood pressure was 90/60 mm Hg. His head and neck, cardiovascular, and abdominal examinations were normal. His skin was cool but warmer than expected given his core temperature; pulses were present in all extremities. There were decreased breath sounds and egophony in the right lower lobe; the signs o consolidation were conf rmed by chest x-ray. What is the cause o this man’s mental status changes and what is his prognosis?

INTRODUCTION

Key Clinical Questions 1

What are the signs and symptoms o hypothermia?

2

What are the most common causes o hypothermia?

3

Does intoxication associated with hypothermia suggest a better or worse prognosis?

4

What are the dangers associated with hypothermia?

5

Who is most likely to die rom hypothermia?

Vital signs are routinely measured or all hospitalized patients on admission, during nursing shi ts and when in usions are being administered. Clinicians should be able to recognize when abnormal temperatures require immediate action to avoid adverse consequences that may be potentially li e-threatening. HYPOTHERMIA PRESENTATIONS Core body temperature is tightly regulated between a normal diurnal range o 36.0°C and 37.5°C. Temperatures below 36.0°C are considered abnormal. Patients admitted to the inpatient service requently have temperature abnormalities on admission or may develop them during the hospital stay. Because o potential li ethreatening causes, it is essential to obtain an accurate measurement o core body temperature. Temperature is most accurately measured by the gold standard methods o intravascular, esophageal, or bladder thermistors. Because these are logistically di cult, temperature is most commonly measured by rectal, oral, and tympanic membrane measurements. Axillary measurements routinely underestimate core body temperature and are not recommended. Interpretation o oral measurements requires consideration o in uences that a ect the results such as eating, drinking, breathing devices, tachypnea, and mouth breathing. Rectal temperatures may be two to three tenths o a degree Celsius higher than actual core body temperature. In rared cutaneous, aural, and oral thermometers are not reliable in patients with hypothermia. The most accurate aural method is a thermistor probe in direct contact with the tympanic membrane, although the ear canal must be ree o cerumen and debris or this to be precise.

■ EXPOSURE HYPOTHERMIA Exposure hypothermia is def ned as an unintentional all in core body temperature below 35.0°C rom exposure to a cold environment. The most common cause is lack o shelter, warm clothing, or heat during the winter months. When environmental exposure to cold ambient temperatures is not obvious, making the diagnosis can be challenging because the presenting signs are o ten subtle and associated with numerous potential diagnoses. The initial phase 665

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Figure 94 1 Osborn wave.

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o hypothermia usually consists o shivering, tachycardia, tachypnea, and peripheral vasoconstriction. Shivering may disappear i hypothermia is prolonged or progresses to severe levels. Other signs include con usion, drowsiness, dysarthria, decreased coordination, and arrhythmias. In moderate hypothermia (28.0-32.0°C), pupillary dilatation, hallucinations, and the phenomenon o paradoxical undressing—the removal o clothes as core temperature drops— may be present. Cardiac mani estations such as bradycardia and arrhythmias begin to develop. Electrocardiographic (ECG) f ndings, such as a prolonged QT interval as well as an Osborn wave, sometimes re erred to as a J wave, may be present (Figure 94-1). The Osborn wave is also seen in severe hypercalcemia, but the QT interval is usually shorter and the patient is more likely to be tachycardic rom volume depletion. Movement arti act rom shivering may also be present on the ECG in patients with hypothermia, especially in the limb leads (with relative sparing o the precordial leads).

PRACTICE POINT

•

Severe (20 Hypotension Con usion or depressed sensorium

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TABLE 94-1 Utility o Clinical Findings or Diagnosing Bacteremia

• Was this patient brought in rom home? I yes, the prognosis • • •

•

• •

•

• •

• •

•

• • •

is worse. Was this patient ound outside? I yes, prognosis is better. Does this patient drink excessive amounts o alcohol or engage in recreational drug use? I yes, prognosis is better. Is it winter, or one o the coldest days o the year? I yes, the likelihood o cold ambient temperatures contributing to pathology increases. Was this person submerged in cold water? I yes, the likelihood o a good outcome is greater than submersion in warm water. Is the patient greater than 65 years? Increased age increases risk o hypothermia. Has the patient recently had a ever? Is this patient at risk or in ection? Does this patient have other signs or symptoms o in ection or sepsis? I yes, an in ection is more likely and prognosis is worse. Has the patient recently undergone extreme exertion under very cold conditions? I yes, the patient may have exposure hypothermia. Is the patient malnourished? I yes, this decreases the patient’s ability to increase basal metabolism. Is the patient taking hypoglycemic medications? I yes, the patient may have become unconscious and unable to avoid excessive cold. Is the patient elderly or rail? I yes, this decreases the patient’s ability to increase basal metabolism. Does this patient have a history o adrenal, thyroid, or pituitary disease? I yes, this places the patient at greater risk because he or she cannot increase basal metabolism. Is this patient taking medications that cause peripheral vasodilation? I yes, this puts patient at risk or excessive heat loss. Is this patie nt taking antipsychotics? I yes, may cause signif cant temperature dysregulation. Does this patient have a history o congestive heart ailure? I yes, portends a worse prognosis. Did this patient just have surgery? I yes, may be due to exposure hypothermia o the operating room or due to large amounts o cool uids or blood products used during the surgery.

THE EXAMINATION The hypothermic patient should immediately undergo a thorough evaluation or sepsis; intravenous lines or indwelling catheters should be considered potential sources and removed i indicated.

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The ollowing questions should be part o a thorough history; these can narrow down the most likely contributing causes o the hypothermia, and can help def ne the prognosis.

LR, likelihood ratio (higher number is better).

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THE HISTORY

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heart ailure. Patients over the age o 65 years admitted or congestive heart ailure with a temperature below 35.2°C (24 breaths/minute. Indications or long-term chronic oxygen therapy are PaO2 ≤ 55 or an SaO2 ≤ 88% at rest (or during sleep or during exertion). During oxygen supplementation, it is important to remember that a PaO2 o 60 mm Hg is approximately equal to an SaO2 o 90%. It is reasonable to aim or a goal o PaO2 o 60 mm Hg in initial treatment o hypoxia, although in certain situations the acceptable threshold level may be adjusted up or down. For instance, in sickle cell anemia, hypoxia associated with cardiac disease, or chest pain, increases above a PaO2 o 60 mm Hg may be important. Those with chronic CO2 retention may need to have a lower goal (usually goal SaO2 o 88%-92%) because o abnormal control o respiration. There are two main oxygen delivery systems: low-f ow and highf ow delivery systems. Low-f ow systems include oxygen delivery by nasal cannula (NC), simple mask, and reservoir mask (partial rebreather and nonrebreather). Low-f ow systems do not deliver a constant inspired oxygen concentration since there is room air entrained into the NC or mask. Changes in inspiratory f ow rate and tidal volumes will entrain more or less room air, changing the actual FiO2 received. High-f ow oxygen delivery systems (eg, venturi masks) maintain the selected FiO2 by using an oxygen f ow rate that is higher than typical inspiratory f ows or a reservoir bag. Nasal cannulas can deliver up to 6 LPM o oxygen. Higher f ow rates become uncom ortable or patients and o ten do not o er additional improvement in oxygen levels. One liter per minute o oxygen delivers approximately 24% oxygen (FiO2 0.24), with each additional liter adding approximately 3% to 4% o oxygen (Tab le 95-3). However, these estimates are very crude and can vary greatly. Di erent respiratory patterns can a ect how much room air is entrained into the mask, there ore mixing room air with delivered O2, resulting in a lower or higher inspired FiO2. Low minute ventilation and hypoventilation will increase the actual inspired FiO2. Prolonged expiratory phase, increased metabolic rate associated with sepsis, and hyperventilation rom exercise will decrease the actual FiO2. There ore, the percent o oxygen supplied by each liter is a rough estimate, and breathing patterns can alter the amount o oxygen actually delivered. Simple masks can deliver up to 50% to 60% oxygen, and require a 5 to 6 LPM f ow rate to avoid buildup o carbon dioxide (CO2) in the mask. A reservoir bag can be attached to a simple ace mask to increase the delivered oxygen to 80% to 85%. A f ow rate o at least 5 to 8 LPM is needed to ensure distention o the bag and to keep CO2 out o the mask. A nonrebreather mask can deliver (in theory) nearly 100% FiO2, by keeping inspiratory gases separate rom expiratory gases by means o a one-way valve. Because these masks do not seal tightly on the patient’s ace, room air can leak in and the FiO2 will be less than 100%. Air entrapment masks, which are requently called venturi masks, can deliver up to 50% FiO2 and are able to supply a constant and predictable FiO2. Oxygen (100%) f ows through a one-way valve and passes by two open ports, incorporating room air. The amount o air entrained depends on the f ow rate and size o the two open ports, and as the inf ow rate increases, less entrained room air is included. There ore, the resultant FiO2 remains constant, which is the main advantage to the venturi mask over simple masks. The venturi mask is ideal in treatment o hypoxia caused by COPD or

x

TREATMENT CONSIDERATIONS

i

A ter ensuring that the patient is not acutely decompensating, a comprehensive history should be obtained to help elucidate the possible cause o hypoxemia. Smoking status, possible occupational exposures, sick contacts, recent travel, and personal medical history may give diagnostic clues to the etiology o the hypoxemia. For instance, a history o COPD, coronary artery disease, cystic brosis, neuromuscular disorder, or stroke can give an indication o the cause o hypoxia. A patient may display signs and symptoms o hypoxia including tachypnea, dyspnea, and cyanosis. Cardiac mani estations include tachycardia, palpitations, arrhythmias, hypotension, chest pain, diaphoresis, and shock. Hypoxia may be evident by the presence o altered mental status, delirium, headache, seizures, obtundation, or tremors. Clinicians must thoroughly assess or these signs and symptoms, and initiate the appropriate workup or the etiology o hypoxia. Con rmation o the diagnosis o suspected hypoxia is based on arterial blood analysis. Evaluation must be initiated early, concurrent with the treatment o acute respiratory ailure and/or hypoxia. The ABG value is used to assist in the diagnosis o hypoxia, di erentiate between acute and chronic orms, and help guide treatment. A chest x-ray (CXR) should be obtained to look or causes o hypoxia such as pneumonia, pneumothorax, pulmonary edema, or masses that can be urther evaluated and treated. A noncontrast computed tomographic (CT) scan o the chest may also be warranted to ollow up an abnormal CXR. A normal CXR in the setting o unexplained hypoxia should raise suspicion or possible pulmonary embolus (PE) as an etiology or acute hypoxia, and can be evaluated with contrast CT scan o the chest (PE protocol), lower-extremity Doppler ultrasound, or V/Q scan.

Hypoventilation will be detected with the correct clinical scenario and an ABG value showing an elevation in PaCO2 without an increased A-a gradient.

a

Evaluation

673

TABLE 95-3 FiO2 of Oxygen Delivery Devices A

P

Oxygen Device

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Nasal cannula 1L 2L 3L 4L 5L 6L Simple oxygen mask 5-6 L 6-7 L 7-8 L Simple mask with reservoir* 6L 7L 8L 9L 10 L Nonrebreather Venturi masks (manufacturer-dependent) 2 or 3 L 4L 6L 8L 10 or 12 L 15 L

Approximate FiO2 % 24 28 32 36 40 44 40 50 60 60 70 80 90 >99 100

24 28 31 35 40 50 or 60

Low minute ventilation and hypoventilation will increase the actual inspired FiO2. Prolonged expiratory phase, increased metabolic rate associated with sepsis, and hyperventilation rom exercise will decrease the actual inspired FiO2. There ore, the amount o oxygen delivered by each device is a rough estimate o the actual amount. *In theory, reservoir masks can deliver near-100% FiO2; however, the FiO2 is o ten 60 mm Hg or SaO2 > 90%. Pulmonary toxicity can occur at higher FiO2 levels, and the goal should be to titrate down to 60% FiO2 and below as tolerated. PEEP is normally set at 5 cm H2O unless the patient has the acute respiratory distress syndrome, which may require higher levels o PEEP. Methods to increase oxygenation (improve PaO2) include increasing FiO2 and PEEP.

■ PULMONARY CONSULTATION Frequently the cause o hypoxemia can be determined and treated without need or pulmonary consultation. However, in complicated cases, or cases in which a patient is unstable, or when considering invasive or expensive testing, a pulmonary consultation can be valuable. The pulmonary consultant should provide a reasonably complete but ocused di erential diagnosis or the patient’s hypoxia, can assist in selecting the appropriate diagnostic tests to con rm the diagnosis, and should also assist in guiding appropriate therapy to correct the hypoxia and its underlying cause.

CONCLUSION In summary, hypoxia is common in the hospital setting and requires close monitoring and treatment. It is important to recognize signs and symptoms o hypoxia, di erentiate between

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Glenny RW. Teaching ventilation/per usion relationships in the lung. Adv Physiol Educ. 2008;32:192-195.

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George RB. Ventilation, gas exchange, and oxygen delivery. In: George RB, Light RW, Matthay MA, Matthay RA, eds. Chest Medicine: Essentials o Pulmonary and Critical Care Medicine. 3rd ed. Baltimore: Williams and Wilkins; 1995:63-78.

o

Branson RD. The nuts and bolts o increasing arterial oxygenation: devices and techniques. Respir Care. 1993;38:672-686.

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SUGGESTED READINGS

i

Our patient’s initial workup included pulmonary unction tests, chest CT, echocardiogram, and ABG. Pulmonary unction tests showed a moderate obstructive de ect, a moderate restrictive de ect, and a severe gas trans er de ect. A CT scan o the chest showed patchy interstitial thickening bilaterally, mild emphysematous changes, cardiomegaly, and a pericardial e usion. ABG on our liters o oxygen revealed a pH o 7.49, PaCO2 o 35 mm Hg, PaO2 o 71 mm Hg, and bicarbonate o 26. B-natriuretic peptide (BNP) was 4347 (re erence range 0-125 pg/ mL). Echocardiogram showed a massively dilated right ventricle with evidence o pressure and volume overload. A bubble study was positive or a patent oramen ovale with right to le t shunting. Severe pulmonary hypertension was also suggested on echocardiogram with a right ventricular systolic pressure o 78 mm Hg. Right heart catheterization conf rmed pulmonary hypertension, showing a mean pulmonary artery pressure o 58 mm Hg. The etiology o her hypoxemia was thought to be secondary to pulmonary hypertension, which was multi actorial in nature. Causes included COPD, interstitial disease rom previous radiation therapy, and obstructive sleep apnea. She was aggressively diuresed, which resulted in improved oxygenation, and was able to be discharged on diuretic therapy with spironolactone and urosemide. She was then started on sildenaf l, a phosphodiesterase-5 inhibitor, as an outpatient in a pulmonary hypertension specialty clinic. Her oxygenation and symptoms improved with this treatment, and she has improvement in her unctional capacity. This patient is now able to leave the house to participate in daily activities, which she was unable to do previously. This case highlights multiple possible causes o hypoxia and the many diagnostic tools available to evaluate hypoxia.

pulmonary etiologies and other possible causes, and treat quickly and appropriately.

a

CASE 95-2

Grippi MA. Respiratory ailure: an overview. In: Fishman AP, Elias JA, Fishman JA, Grippi MA, Kaiser LR, Senior RM, eds. Fishman’s Pulmonary Diseases and Disorders, 3rd ed. New York, NY: McGrawHill; 1998:2525-2535. Hall JB, Schmidt GA, Wood LDH. Acute hypoxemic respiratory ailure. In: Murray JF, Nadel JA, eds. Textbook o Respiratory Medicine. 2nd ed. Philadelphia, PA: WB Saunders; 1994:2589-2613. The Acute Respiratory Distress Syndrome Network. Ventilation with lower tidal volumes as compared with traditional tidal volumes or acute lung injury and the acute respiratory distress syndrome. N Engl J Med. 2000;342:1301-1308. Wahr JA, Tremper KK. Noninvasive oxygen monitoring techniques. Crit Care Clin. 1995;11:199-217. Ward, JJ. High-f ow oxygen administration by nasal cannula or adult and perinatal patients. Respir Care. 2013;58:98-122. West JB. Ventilation-per usion relationships. In: Coryell PA, ed. Respiratory Physiology: The Essentials. 5th ed. Baltimore, MD: Williams and Wilkins; 1995:51-69. Williams AJ. ABC o oxygen: assessing and interpreting arterial blood gases and acid-base balance. BMJ. 1998;317:1213-1216. Wood KE. Major pulmonary embolism: review o a pathophysiologic approach to the golden hour o hemodynamically signi cant pulmonary embolism. Chest. 2002;121:877-905.

675

96

CHAP TER

Sleep Disturbance in the Hospitalized Patient Xi Chen, MD, PhD Mihaela H. Bazalakova, MD, PhD

Key Clinical Questions

676

1

What are common causes o sleep disturbance in hospitalized patients?

2

How do you approach the patient complaining o sleep disturbance?

3

Which inpatient populations are at high risk o sleep disturbance, and what are the corresponding common primary or secondary sleep problems?

4

How do you choose a hypnotic agent based on etiology o insomnia and medical comorbidities?

5

What are the nonpharmacologic behavioral alternatives in cases o insomnia, hypersomnia, or sleep disturbance secondary to circadian mismatch?

EPIDEMIOLOGY Sleep remains one o the least understood physiological processes, despite the signi cant percentage o our lives spent in the sleep state. As such, it is at the modern day rontier o not only scienti c inquiry but also clinical knowledge and practice. Perhaps nowhere is this better illustrated than in the inpatient setting where, despite our increasing understanding o the wide-ranging role o sleep on a spectrum ranging rom mood and attentiveness to metabolic physiology to molecular signaling in the healthy state, little e ort is expanded to optimize sleep quantity and quality during acute illness and recovery. In act, little is known about sleep architecture, duration, and disturbance in the inpatient setting, and correlates o sleep variables with clinical outcomes. However, it is estimated that approximately one-third o hospitalized patients have insomnia at the time o admission. Additionally, up to 69% o postsurgical patients continue to complain o prolonged sleep problems a ter hospital discharge. The high prevalence o sleep disturbance among this population warrants the evaluation and treatment o sleep problems as part o routine hospital care. Early recognition and treatment o sleep complaints may improve recovery among hospitalized patients. Sleep disturbance in the outpatient population, primarily as investigated in the context o obstructive sleep apnea (OSA) associated both with recurrent hypoxemia but also recurrent arousals resulting in sleep ragmentation and sympathetic overactivation, has been implicated in increased morbidity and mortality in a variety o cardiovascular (re ractory hypertension, congestive heart ailure [CHF], atrial brillation, stroke), metabolic (insulin resistance, diabetes, obesity), and psychiatric (mood disorders, anxiety) phenotypes. Outside o OSA, sel -reported, and there ore subjective, short (10 hours) overnight sleep duration have both been associated with increased cardiometabolic morbidity and mortality in large epidemiological studies. This, at rst glance contradictory, proposed inverted U shape relationship o sleep duration and mortality may be due to two aspects o sleep. The rst re ers to the current leading hypothesis as to the primary purpose o sleep, namely a “restorative” anabolic unction, perhaps especially o slow-wave or “deep” sleep, the latter necessary or growth hormone secretion. The hypothesis is that persistently shortened sleep duration, either due to overall shortened sleep zone or recurrent sleep interruption, may curtail the organism’s chance o physiological restoration. Indeed, studies o chronic partial sleep deprivation in humans demonstrate metabolic disturbance with decreased leptin (satiety hormone) and increased ghrelin (appetite stimulating hormone) secretion, hypothermia due to impaired temperature regulation, acute insulin resistance equivalent to a prediabetic state, and hypothalamic-pituitary-adrenal axis dysregulation with elevated levels o thyroid stimulating hormone (TSH) and increased evening cortisol secretion among others. Mice exposed to complete sleep deprivation die due to overwhelming sepsis, re erencing another important physiological unction o sleep, through incompletely understood mechanisms: immune system regulation and unction. The relationship between sleep and the immune system appears to be bidirectional, and objective hypersomnia or increased sleep duration is certainly observed in the context o increased proinammatory cytokine secretion, including interleukins 6 (IL-6) and 1beta (IL-1β) and tumor necrosis actor-alpha (TNF-α), during acute illness. This has been hypothesized as a potential explanation or the

A. Sleep maintenance or initiation insomnia and/or secondary daytime sleepiness/ atigue: 1. Obese patients (body mass index (BMI) > 35 kg/m 2), especially with truncal pattern o obesity and/or large neck circumerence (>17 in men, >14 in women), crowded posterior

C H A P T E R 9 6 S l e e p D i s t u r b a n c e i n t h e H o s p i t a l i z e d P a t

2. Diabetes and hyperthyroidism are associated with insomnia independently o OSA, due to a multitude o actors including pain ul neuropathy and diuresis, and anxiety and requent awakenings respectively. 3. Renal ailure, pregnancy, and synucleopathies (Parkinson disease [PD], multiple systems atrophy [MSA], Lewy Body Dementia [LBD]) are some o the conditions highly associated with restless leg syndrome (RLS) and/or comorbid periodic limb movements o sleep (PLMS), at least partially due to a relative iron-de ciency state and/or dopaminergic dysregulation. Depletion o iron stores in the context o requent phlebotomy, bleeds or postoperatively, is also likely to worsen RLS/PLMS acutely. Exacerbation o RLS/PLMS, which o ten

i

Multiple aspects o the inpatient experience lower the threshold or sleep disturbance, including environmental noise, pain, medication side e ects, and psychophysiological stress. However certain patient populations may be at higher risk o notable sleep disruption, especially exacerbations o primary sleep disorders. Although by no means exhaustive, a list o patient populations predisposed to primary or secondary insomnia, circadian misalignment and hypersomnia, are summarized in Table 96-1 and described below:

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RISK FOR SLEEP DISTURBANCE

See Chapter 235 (Sleep Apnea and Obesity Hypoventilation Syndrome).

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■ RISK STRATIFICATION—PATIENT POPULATIONS AT

oropharyngeal anatomy (Mallampati airway classi cation III-IV) due to relative macroglossia, narrowed anterior-posterior or lateral diameters and low-sloping so t palate, or cranio acial eatures including notable overbite or retrognathia, micrognathia, mid ace hypoplasia, or narrowed maxillary dental arch with high-arched palate; postmenopausal women, A rican American, and Asian American populations with above exam ndings: these patients may be at high risk o OSA (which may present with nocturnal snoring, witnessed apneas, gasping arousals, sleep maintenance, and/or initiation insomnia) or daytime symptoms (excessive daytime sleepiness [EDS] or atigue). While beyond the scope o this chapter, OSA evaluation with screening questionnaires such as the STOP-Bang, and typically outpatient, objective sleep testing once acute medical issues have stabilized, should be considered in all patients with re ractory hypertension (resistant to three or more antihypertensive agents), early onset primary hypertension, atrial f brillation (where central apnea or periodic obstructive breathing are also highly prevalent), congestive heart ailure, and poorly controlled diabetes or hypothyroidism.

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association between subjectively reported long sleep and increased morbidity, with hypersomnia or at least subjective hypersomnolence the “readout” o underlying in ammation due to systemic illness. As little as we know about sleep and hence our limited means to regulate not only sleep duration, but also sleep architecture or sleep stage cycling, given the relationships between sleep and physiology as described above, it is likely to serve acutely ill patients well to, at minimum, minimize sleep disruption in the inpatient and recovery setting. A recent study examined risk actors or sleep disturbance during hospitalization and ound that the severity o comorbid conditions and poor per ormance o activities o daily living (ADL) predicted sleep complaints during admission. Physician awareness o the impact o sleep disturbance in hospitalized patients is vital since about hal o patients admitted on general medical wards will complain o sleep disruption. In this chapter, we will examine the major categories o sleep disturbance, common etiologies, and diagnostic and therapeutic approaches.

TABLE 96-1 Medical Comorbidities o Common Primary Sleep Disorders Sleep Disorder Sleep apnea, obstructive (OSA), central (CSA) or Cheyne Stokes respiration (CSR) Restless leg syndrome (RLS)

Circadian misalignment

Clinical Features Nocturnal (snoring [less prominent in women], apneas, gasping arousals, sleep maintenance and initiation insomnia). Daytime (nonre reshing sleep, atigue (women), excessive daytime sleepiness (men), anxiety. Sensory-motor leg, arm or torso disturbance described as “achy,” “crawling,” “pulling,” “prickling,” or “tingling,” sensation, desire to move, sometimes involuntary hyperkinetic movements with triple lexion o the lower extremities, worsened by rest and circadian phase (worse at night), improvement by movement. May lead to sleep initiation and maintenance insomnia. Mismatch between internal circadian sleep-wake cycles and the external environments. Insomnia resolves when patients are allowed to determine sleep timings and duration.

Hypersomnia

Excessive sleepiness despite ample sleep opportunity.

Insomnia

Di iculty initiating or maintaining sleep, early awakenings, nonre reshing sleep, daytime dys unction.

Patient Populations at Risk Obesity, early onset or re ractory (three or more antihypertensive medications) hypertension, atrial ibrillation, heart ailure, symptomatic postmenopausal women, DM, hypothyroid Iron de iciency anemia, hypo erritinemia ( erritin < 50), acute bleeds or phlebotomy, pregnancy, renal ailure, synucleopathy (PD, MSA, LBD), rapid opiate taper (rebound RLS), prolonged immobilization, untreated OSA, TCAs, SSRIs, CCBs

Elderly patients (advanced phase, irregular sleep-wake times); tauopathy (Alzheimer disease), TBI, hepatic cirrhosis, adolescents and young adults (delayed phase); congenital blindness ( ree-running non–24-h disorder) TBI, hypoventilation (obesity, neuromuscular, scoliosis), hypothyroid DM, hyperthyroid, mood disorders, anxiety, substance use disorder, withdrawal rom hypnotics, sedatives, opiates

American Academy o Sleep Medicine. International Classi ication o Sleep Disorders-3, Revised: Diagnostic and Coding Manual. Chicago, IL: American Academy o Sleep Medicine; 2014.

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present with sleep initiation and/or maintenance insomnia due to sensory-motor disturbance (creepy-crawly or achy sensations and/or involuntary small amplitude nonsustained hyperkinetic movements) involving the leg, arms, or torso, worsened at rest, relieved by movement, and presenting in a circadian ashion typically worse in the evening-night time hours, should also be considered in the context o withdrawal or diminished dosing o long-standing opiates, as opiates constitute one o the most e ective RLS treatments, and taper or discontinuation can result in RLS-related insomnia, or example, in the postoperative setting where rapid opiate tapers are requently used. Tricyclic antidepressants, antiemetics with antidopaminergic actions, such as metoclopramide or prochlorperazine, and calcium channel blockers, are among the known exacerbators o RLS/PLMD. 4. Patients with history o drug use disorders, notably chronic alcohol use, are likely to experience signi cant sleep initiation and maintenance insomnia upon abrupt cessation o alcohol intake. While acute alcohol ingestion results in shorter sleep latency and initial slow wave sleep increase, increased nocturnal awakenings and rapid eye movement (REM) sleep rebound are characteristic in the latter hal o the sleep cycle, requently resulting in nonre reshing sleep, nightmares, and lower arousal threshold with shortened overall sleep duration. Abrupt abstinence due to hospitalization may not only cause short term sleep initiation dif culties, but may unmask underlying sleep initiation insomnia. High level o clinical suspicion should be maintained not only or primary insomnia but comorbid anxiety or mood disturbance, with alcohol use as sel -medication or above. B. Circadian misalignment, or insomnia due to sleep-wake circadian mismatch. Frequently masquerading as sleep initiation insomnia, dif culty with sleep initiation is o ten due to mismatch between innate circadian sleep-wake timings and the environmental or social night-day cues. The key distinction is the resolution o insomnia i the patient is allowed to sleep ad lib, or whenever they eel sleepy and or as long as they require. Thus someone who requires >30 minutes and o tentimes on the order o hours in order to initiate sleep regardless o the time o day indeed should be considered as experiencing insomnia. In contrast, a patient who has dif culty initiating and/or sustaining sleep at 10 PM, but will easily all asleep at 2 AM and subsequently sleep or an acceptable 7 to 8 hours, is displaying circadian mismatch with, in this example, delayed sleep phase. Elderly patients and patients with neurodegenerative processes, including but not limited to Alzheimer disease, are prime candidates or circadian disruption, as levels and circadian oscillation o melatonin, the endogenous hormone regulating circadian e ects on sleep, appears to dampen with age and in neurodegeneration, including Parkinson disease. Medications, especially lipophilic β-blockers such as propranolol, have also been associated with melatonin suppression. Patients may present with advanced (early sleep times and early awakenings) or delayed (late sleep onset and wake, to the point o complete day-night inversion) sleep phase respectively. Elderly patients with or without dementia are also more prone to irregular sleep-wake cycles, where sleep is poorly consolidated throughout the 24-hour cycle, and one or more daytime naps lower the sleep drive and contribute to sleep initiation and maintenance dif culties, and nocturnal awakenings with variable return latencies. Patients with hepatic cirrhosis, traumatic brain injury (TBI) patients su ering rom postconcussive syndrome, as well as teenagers or young adolescents are particularly prone to circadian mismatch with delayed circadian sleep phase, or the “night owl” sleep phenotype. 678

Congenitally blind patients, or patients with retinal pathology, including retinitis pigmentosa, are at risk o non–24-hour or “ ree-running” circadian disorder where the sleep zone dri ts later or delays by minutes to hours on a daily basis, corresponding to our natural circadian period which is slightly longer than 24 hours, and which is not entrained to light/dark stimuli in blind patients, until the patient’s sleep zone “marches around the clock.” C. Hypersomnia, or excessive daytime sleepiness in the absence o sleep initiation or maintenance insomnia, or in the presence o adequate sleep opportunity. Certainly acute illness is requently accompanied by hypersomnia or atigue, likely in large part secondary to elevated cytokine secretion, including elevated levels o IL-6 and TNF-α. However, persistent sleepiness or atigue in the postacute convalescence state can limit participation in physical and occupational therapy and opportunity or placement with higher level acute rehab due to lack o patient participation. Patients with primary hypersomnias such as narcolepsy or long (>10 hours/24 hours) sleep requirement at baseline can experience rebound hypersomnolence in the context o inpatient discontinuation o wake promoting agents such as over the counter ca eine, requently also sel -prescribed or subjective atigue or sleepiness; sympathomimetics (methylphenidate or amphetamine derivatives), moda nil/armoda nil, or amantadine, requently used in attention de cit (ADD) or attention de cit and hyperactivity (ADHD) disorders or antidepression augmentation therapy, or antidepressives with wake promoting properties (including buproprion and venla axine). Prompt resumption in these medications should be considered as soon as the clinical circumstances allow it. A likely underdiagnosed entity is ob esity hyp oventilation syndrome (OHS), which should be considered in patients with hypersomnolence, headaches upon awakening, morbid obesity or BMI >35 to 40 kg/m 2, and serum HCO3 >27 mEq/L not explained by alternative causes, such as contraction alkalosis rom diuretic use. Both insomnia and hypersomnia have been described posttraumatic brain injury (TBI), with hypersomnolence encountered more commonly. Rarely, signi cant TBI can result in secondary narcolepsy, with loss o hypocretin secreting hypothalamic neurons and resultant sleep attacks or cataplexy (emotionally induced weakness with preserved consciousness). INSOMNIA By ar, insomnia is the most common sleep complaint among patients in both ambulatory and hospital settings. The prevalence o chronic insomnia is high, with approximately 20% to 30% o the general population reporting ongoing symptoms. Chronic insomnia is associated with decreased quality o li e, daytime unctional limitations, chronic pain, increased risk o medical and psychiatric illnesses, substance abuse, increased utilization o health services, and increased risk o death. The International Classif cation o Sleep Disorders (ICSD-3), published by the American Academy o Sleep Medicine (AASM), de nes insomnia as dif culty initiating or maintaining sleep, waking up too early, or sleep that is chronically nonrestorative or perceived to be poor in quality. To meet diagnostic criteria or insomnia, these symptoms must be associated with daytime mental or physical sequelae that impair the unctional status o the individual. Insomnia may be a primary disorder or may be comorbid with another physical or mental illness. EVALUATION Assessment and evaluation o any sleep problem begins with an initial interview o the patient and amily, as well as a review o the medical record or documentation o preexisting primary sleep disorders and any actor that could exacerbate or contribute to the

C H A P T E R 9 6 p D i r b a n c e i n t h e H o s p i t a l i z e d P a t i e n

Light, especially blue-spectrum, but also high intensity (10,000 lux), physical activity, and ood intake, are among the most potent “zeitgebers,” or entrainers o the intrinsic circadian night to the external or environmental day/night light/dark cycle. Melatonin secretion is exquisitely sensitive to light but, and this is a crucial point or the clinical use o light therapy to modi y sleep timings, in a time-dependent manner. Speci cally, light exposure prior to the nadir or body temperature, delays the sleep zone or results in a “night-owl” phenotype. Conversely, light later than or ollowing the body temperature nadir, advances the sleep zone, or results in a “morning lark” phenotype. The body temperature nadir is itsel dependent on the circadian pattern, and in general occurs approximately 2 to 4 hours prior to the circadian wake time in a patient with a sleep zone o average duration (8 hours). Thus, in a “normal” individual, with a sleep zone o 10 PM to 6 AM, the body temperature nadir may occur around 4 AM—light between 7 PM and 4 AM will delay the circadian phase and predispose to later bed and wake times, while light exposure between 4 AM and 8 AM will advance the circadian phase and predispose to earlier bed and wake times. Light in the middle o the day, that is, noon or earlya ternoon has minimal e ect on the circadian phase and sleep-wake timings. However, in a patient with a delayed sleep phase, and a sample sleep zone o 2 AM to 10 AM, light exposure at 6 AM will likely precede the body temperature nadir, and will in act result in circadian delay, instead o the desired circadian advance to earlier bedtimes and wake time. While the circadian phase may be determined with urinary or salivary melatonin measurements, this is a labor intensive procedure which ideally has to be per ormed in complete darkness, controlled physical activity and ood intake levels, is not clinically validated in outpatients, and is likely to be a ected by underlying pathophysiology in the hospitalized patient. Instead, to estimate the patient’s underlying circadian “baseline” the question may be posed: “when healthy, and a ter a week o sleeping ad lib, or example during vacation, which would correct or sleep deprivation and resultant sleep rebound, what would you estimate as your ideal sleep zone timing and duration. In other words, when would you naturally pre er to go to sleep and wake up.” Similarly, an estimation o the sleep pattern over the past 2 to 3 days by patient and/or amily or nursing sta , either by recall or acilitated by sleep diaries, gives an idea o the current state o the patient’s circadian phase. Timed exposure to high intensity light (10,000 light boxes), as well as avoidance o light at crucial times, and low-dose melatonin (0.5-3 mg) may be used as chronotherapy to regulate the timing and consolidation o the sleep zone in the hospitalized patient. The general rules are as ollows: avoid bright, high intensity and blue spectrum enriched light (which is emitted by screens including tablets, personal phones, laptops and TV screens) or 2 to 3 hours prior to desired bedtime; i screen use is necessary, use blue-light blockers or dim screen intensity. At that time also administer low-dose

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evaluation and treatment interventions to promote uninterrupted sleep at night. Care ully review the medication list and consider whether the drugs themselves, the dosing regimens, or the methods o administration are disrupting sleep (see Table 96-2). I possible consider changing drugs or altering the timing o administration. An algorithm or diagnosing and treating sleep problems in hospitalized patients is outlined in Figure 96-1. By ollowing these steps, the provider may develop a treatment plan that addresses primary sleep disorders, untreated comorbidities, and iatrogenic causes o poor sleep.

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current situation. Obtain a ocused history by using questions listed in Table 96-3 to characterize the onset, duration, requency, and speci c characteristics o the patient’s current sleep patterns. The rst question in the evaluation o insomnia is whether sleep initiation and maintenance dif culty is dependent on timing o sleep. I a patient reports sleep initiation dif culties at a certain desired bedtime, but upon re ection they are not sleepy at this time (even though they may be atigued), and they all asleep readily and sleep well when naturally sleepy at an earlier or, more commonly, later time, then the problem is one o circadian mismatch, rather than insomnia. Sleep regulation is a balance between a homeostatic “sleep drive” or “sleep debt” and the intrinsic body clock, or circadian pacemaker. The homeostatic sleep drive is directly proportional to wake ulness duration, that is, the longer one is continuously awake, the higher their sleep drive. The circadian variation o sleep and wake is regulated at least partially by melatonin, a hormone produced by the pineal gland under regulation rom the master pacemaker, the suprachiasmatic nucleus. Melatonin levels begin rising 2 to 3 hours prior to the onset o the circadian night, remain elevated throughout the sleep zone, and decrease coincident to the end o the circadian night. Next, establish whether the onset o the patient’s sleep complaint began at the time o hospitalization. I the sleep disruption began with hospitalization, subsequent questions (Table 96-4) may then ocus on hospital actors that may be impairing sleep, such as altered sleep hygiene or, more commonly, medication side e ects (Table 96-2). Inquire about the use or abuse o substances such as hypnotics (rebound insomnia and/or anxiety upon discontinuation), stimulants (including over-the-counter ca eine) (rebound hypersomnia and/or depression upon discontinuation), antidepressants and antiepileptic drugs (AEDs) (rebound insomnia or hypersomnia depending on the mechanism o action and individual agent), and opioids (rebound RLS exacerbation and/or pain resulting in insomnia). Ask questions about pain syndromes, nocturnal gastroesophageal re ux, and other symptoms that o ten impact sleep. The next step is to assess or preexisting mood, anxiety, psychotic, and substance use disorders, all o which may be exacerbated during an acute hospitalization. Substance abuse disorders are also associated with sleep problems. Over hal o patients undergoing alcohol rehabilitation exhibit symptoms o insomnia, such as increased sleep latency during the 6 months prior to entering treatment, and many report using alcohol or the purpose o initiating sleep. Indeed, untreated insomnia and other sleep problems may increase the risk o developing substance abuse problems due to “sel -medicating” with alcohol and other substances to help with sleep. While alcohol and illicit substance intoxication and withdrawal are known to disrupt sleep directly, sleep disturbances may persist long a ter withdrawal symptoms have abated, sometimes years later. Be ore prescribing a sleep agent, assess or the presence o suboptimally treated medical, neurologic, psychiatric conditions, or a primary sleep disorder (see Tables 96-1 and 96-2). Care should be taken to rely only on sound, documented evidence or a con rmatory medical history when ormulating the diagnosis. For example, a patient may state that he has “apnea” because his wi e speculates this, but he has never had a ormal evaluation or OSA. Lastly, evaluate the extent to which environmental actors such as noise level, various therapies, and hospital routines may be impairing sleep. Discuss the importance o maintaining a quieter environment with key sta members. When available, relaxation tapes, massage, and warm (nonca einated) beverages are pre erable to pharmacologic strategies, as shown in Table 96-6. In addition, limit potential iatrogenic causes o disrupted sleep by using alternative drugs or drug regimens, and consider altering

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TABLE 96-2 Selected Drugs, Common Clinical Uses and Side E ects

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Drug Class CNS TCAs

Common Uses

Side Effects/Caution

Amitriptyline, imipramine, nortriptyline, desipramine, doxepin, clomipramine Fluoxetine, sertraline, citalopram, escitalopram, paroxetine

Insomnia and comorbid migraine and mood disorders, concussive symptoms including tinnitus, headache, vertigo Insomnia and comorbid depression/anxiety. Suppress REM sleep and, there ore, reduce cataplexy Hypersomnolence with comorbid depression/anxiety, RLS/PLMD (only antidepressant not associated with RLS/ PLMD exacerbation). Smoking cessation Insomnia and comorbid depression. Venla axine is e ective or perimenopausal hot lashes and associated insomnia Hypersomnia. Circadian mismatch

Very sedating. Risk o daytime “hangover” sedation, urinary retention, constipation, orthostatic hypertension, weight gain. Can worsen RLS/PLMS, RBD, and suicidality in bipolar disorder Some patients experience activation rather than sedation. Can worsen RLS/PLMD, unmask RBD, risk o suicidality with bipolar disorder

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Examples of Drugs

SNRI

Venla axine, duloxetine

Stimulants

Ca eine

Sympathomimetics

Methylphenidate, amephatminederivatives

Hypersomnia, comorbid depression, ADD/ADHD, long sleepers, circadian mismatch

Wake promoting

Moda inil, armoda inil

Same as sympathomimetics, but no cardiovascular side e ects, pre erred in comorbid HTN, CAD, h/o substance use d/o

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Buproprion

Cardiovascular Lipophilic β Propranolol, pindolol, blockers metoprolol, timolol Ca2+ channel blockers

Amlodipine, verapamil, ni edipine

Diuretics Other Opioids

HCTZ, urosemide

NSAIDs Methylxanthine Antihistamines

Corticosteroids Quinolone

Codeine, morphine, oxycodone

Activating in some patients; sedating in 12%-31%. I keeps patient awake, switch to AM dosing. I sedating, switch to PM dosing. May cause vivid dreams or nightmares, and exacerbate underlying anxiety disorders such as posttraumatic stress disorder Activating. Avoid a ter 6 PM. Anxiety, GI upset, diuresis. However, appears sa e to bene icial in dose-dependent ashion in CHF, cardiac arrhythmia patients Relatively contraindicated in coronary artery disease (CAD), coronary vasospasm, hypertension, h/o susbstance use d/o. May worsen insomnia, anxiety, nausea, headaches, lower seizure threshold Headaches, decrease OCP e ectiveness, risk o SJS. May worsen insomnia, anxiety, nausea

Fatigue, nightmares. Suppress melatonin secretion and can a ect circadian phase. Atenolol is nonlipophilic and thus less associated with sleep disturbance ↓ Lower esophageal sphincter tone → nocturnal gastroesophageal re lux → sleep disturbance. Exacerbated RLS/PLMD Nighttime diuresis → requent awakenings → ↓ sleep Insomnia and comorbid RLS

Ibupro en, indomethacin, Insomnia and comorbid pain celecoxib Theophylline Insomnia and comorbid nocturnal asthma Diphenhydramine, Over the counter sleep aids promethazine

Dexamethasone, prednisone Cipro loxacin, spar loxacin, o loxacin, grepa loxacin, levo loxacin

Can exacerbate headaches, insomnia. Known to increase REM sleep and thus exacerbate narcolepsy/ cataplexy. May lower seizure threshold

Very e ective or RLS/PLMD symptoms. Quick tapers or abrupt discontinuation can lead to rebound RLS and worsening o insomnia. Use with caution in hypoventilators May increase nocturnal arousals and cause sleep ragmentation Causes less rest ul sleep. May increase arousal requency May have paradoxical e ect on children. Can disrupt sleep i associated with delirium. E ective or sleep onset insomnia, but limited by quick tolerance and sedation “hangover.” Can exacerbate RLS/PLMD Can disrupt sleep, ↑ anxiety, induce mania or psychosis Activating. Consider sleep agent a ter maximizing sleep hygiene. Linezolid rarely causes sleep disturbances

(continued )

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C H A P T E R 9

Insomnia and RLS, synucleopathy (PD, MSA, LBD)

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Side Effects/Caution Can cause sedation or paradoxical insomnia. Watch out or augmentation or worsening o RLS (earlier onset, extension and worsening o symptoms), orthostasis, impulse control behavior dysregulation, including gambling, uncontrolled spending, sex, overeating Insomnia with higher doses. Discontinuation may results in REM rebound with nightmares, increased awakenings, neuroleptic malignant syndrome. RLS augmentation

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Common Uses Insomnia and RLS, synucleopathy (PD, MSA, LBD), comorbid depression

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Examples of Drugs Ropinirole, pramipexole

2. Sleep disordered breathing Treatment o OSA with positive airway pressure (PAP), continuous (CPAP) or more commonly auto (APAP), is shown to improve control o re ractory hypertension, at least partially by restoring nocturnal blood pressure dipping by reducing arousals, sleep ragmentation,

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Although nonpharmacologic therapies are ideal, it may be di cult to provide these in the hospital setting, or they may be only partially e ective in resolving the sleep problem. In these instances, pharmacologic strategies may be needed. Care must be taken in choosing the appropriate drug due to increased risk o side e ects and drug-drug interactions in sick patients. To choose an appropriate sleep agent, evaluate the drug’s ef cacy/pharmacokinetics, mechanism o action, and side-e ect pro le. Then match these characteristics with the patient’s clinical condition(s). Some common scenarios include: 1. In patients with comorbid sleep and psychiatric problems, consider using a sedating psychotropic at bedtime to promote sleep. 2. Avoid TCAs or SSRIs in patients with RLS/PLMS. However, consider TCAs in patients with comorbid migraines or postconcussive syndrome.

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sympatho-activation and endothelial and oxidative damage due to recurrent hypoxemia; ejection raction in CHF; recurrence o atrial brillation ollowing cardioversion; and perioperative morbidity. AutoPAP should be avoided in congestive heart ailure due to the high incidence o Cheyne Stokes respiration, periodic obstructive breathing, and PAP-exacerbated central apnea, all o which can be worsened by high pressures. Bilevel should be considered in the hypoventilating patient, where ventilation with CO2 reduction is the goal, in addition to or instead o resolution o obstructive breathing and recurrent hypoxemia.

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melatonin (0.3-3 mg). Melatonin at bedtime is rarely help ul as a hypnotic, although certain individuals are more sensitive to melatonin’s e ects than others. It is most e ective as a chrono-agent administered 2 to 3 hours prior to bedtime, or 12 hours prior to wake times. Side e ects o melatonin include headache, nightmares, and “hangover” in the morning. Light should be minimized throughout the sleep zone, while bright light (pre erably close to 10,000 lux, ull spectrum or blue light-enriched), should be instituted as close to wake time as possible or a minimum o 15 to 30 minutes. Side e ects o light therapy include mania and headaches. Direct retinal exposure should be avoided to minimize chance o photodamage. It is essential to maintain the same wake time, rather than bed time, every day, as this resets the circadian cycle. Food and physical activity should be encouraged close to wake time. Daytime napping should be minimized. Initially, this may result in temporary sleep restriction, which in turn heightens the sleep drive and acilitates sleep initiation, maintenance and consolidation. In a patient with circadian mismatch, the same principles apply, with gradual change in wake times, bed times, time o melatonin intake and light exposure advanced or delayed by an hour every 1 to 3 days or delayed and advanced sleep phase phenotypes respectively.

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TABLE 96-2 Selected Drugs, Common Clinical Uses and Side E ects (Continued)

TABLE 96-3 Summary o Questions in a Focused Sleep History o Hospitalized Patients Focus Sleep pattern

Behavioral actors Environment Patient com ort

Substances Psychosocial

Examples of Questions When did the sleep problem start? What time do you try go to sleep? How long does it take you to all asleep? How o ten do you wake up during the night? What wakes you up at night? How long does it take you to all back asleep? What time do you wake up? What wakes you up in the morning? How long are you sleeping during the day (naps)? How does your sleep at home compare with your sleep in the hospital? Does the lighting or noise level in the hospital disrupt your sleep? How so? Are you awakened rom sleep or tests, monitoring, bathing, or other nursing/medical procedures? Is your pain adequately controlled at night? I not, are you on a scheduled analgesic regimen, or do you have to ask or pain medications? Do you have breathing problems, gastroesophageal re lux, or some other type o discom ort that keeps you rom sleeping well? Do you drink alcohol? How much, and how o ten? When was your last alcoholic beverage? Do you use cocaine, methamphetamine, marijuana, or other substances? When was your last use? How was your mood just prior to being hospitalized? How has your mood been since you were admitted? Have you experienced any emotionally or physically traumatic event just prior to your hospitalization? Have you had any treatments or procedures during this hospitalization that were particularly bothersome to you (eg, intubation, resuscitation, surgery, blood draws, magnetic resonance imaging scan)?

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TABLE 96-4 Common Sleep Barriers in the Hospital and Potential Solutions

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Barriers Noise and lighting

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Strategies to Optimize Sleep in the Hospital Limit the volume level o audiovisual and other electronic equipment (eg, televisions, radios, handheld games). Promptly respond to alarm monitors; consider liberalizing the monitor alarm setting. Keep patients’ doors closed, i appropriate. Post signs to remind sta to minimize conversations at or near the bedside. Switch beepers and other electronic devices to “vibrate” at night. O er earplugs and eye masks. Encourage exposure to brighter light during the day (turn on the lights, open the curtains), and turn o the lights by 8 PM. In shared hospital rooms, have patients and their visitors meet in another location (eg, con erence room, ca eteria). Request that patients and their visitors turn o the ringer on their cell phones. Adhere strictly to visiting hours. Encourage visitors to minimize discussing emotionally di icult topics with patients near bedtime. Encourage patients to limit contact with anxiety-provoking individuals, especially in the evening. Minimize use o benzodiazepines or sleep. Try to wean patients o benzodiazepines prior to discharge. Avoid starting multiple medications at one time. Minimize use o sleep-disrupting medications. Change medication regimens to promote sleep (eg, avoid night-time diuretics i possible). No ca eine or cigarette smoking a ter 6 PM. Encourage regular nocturnal sleep time, and discourage lengthy naps during the day. Minimize bathing, dressing changes, room switches, and other activities at night. Regularly review nighttime orders to see i you could decrease the requency o overnight monitoring. Provide an updated calendar to acilitate cognitive orientation. Discontinue nonessential medications. Minimize use o benzodiazepines, barbiturates, opiates, antihistamines, and anticholinergic agents. Regularly provide verbal and other cues to orient patients to the date, time, location, and circumstances. Optimize nighttime glycemic control and maximize pain management. For patients with re lux: No oral intake a ter 8 PM, and keep head o bed elevated ≥30°. Provide nocturnal O2, CPAP, and/or other medications, as appropriate. I patient is on CPAP, assess the mask’s it and com ort.

CPAP, continuous positive airway pressure.

3. Avoid benzodiazepines in patients with history o drug use disorders and hypoventilation, because o dependence/abuse potential and risk o respiratory depression, respectively. The US Food and Drug Administration (FDA) has approved ve classes o medications or the treatment o insomnia: benzodiazepine GABAA receptor agonists, nonbenzodiazepine GABAA receptor agonists (non-BzRAs), melatonin-receptor agonists, low-dose tricyclic antidepressants, and, most recently, orexin receptor antagonists (Table 96-5). Benzodiazepines include estazolam (ProSom), urazepam (Dalmane), quazepam (Doral), temazepam (Restoril) (notable or intermediate hal -li e), and triazolam (Halcion) (notable or a short hal -li e). Flurazepam and quazepam have long hal -lives, increasing the risks o side e ects and drug interactions, and should generally be avoided in hospitalized patients. For similar reasons, it is prudent to avoid use o other long-acting benzodiazepines such as clonazepam (Klonopin) and diazepam (Valium), unless there is a speci c indication such as RLS. All benzodiazepines except lorazepam, oxazepam, and temazepam have signi cant hepatic metabolism and should be used with caution in patients with liver disease. Although non-BzRAs are structurally unrelated to benzodiazepines, they also act at the GABAA receptor, and have many similar characteristics and risks. These agents include eszopiclone (Lunesta), which is most e ective in sleep maintenance insomnia due to having the longest hal -li e and has mild antianxiety properties due to af nity at the α 2 and 3 subunits o the GABAA receptor; zaleplon 682

(Sonata) which can be used as needed or middle o the night awakenings due to its very short hal -li e, zolpidem (Ambien), and zolpidem extended-release (Ambien CR) which are use ul or both sleep initiation and maintenance insomnia. Both benzodiazepines and non-BzRAs have a risk or abuse and dependence. Although there is much less risk o dependence with the nonbenzodiazepines, it appears prudent to avoid using all o these agents to treat insomnia in patients with a prior history o sedative-hypnotic or alcohol dependence. Side e ects o benzodiazepines include daytime sedation, anterograde amnesia, cognitive impairment, incoordination, dependence, tolerance, rebound insomnia, and, importantly, respiratory depression. The side-e ect pro le o non-BzRAs is generally similar but appears to be less severe. Additionally, zolpidem and eszopiclone have been associated with delirium-like episodes, hallucinations, and sleep behaviors, including sleep walking and sleep-related eating disorder, which can be exacerbated in the hospital setting. Long-acting agents should not be used in the elderly due to increased risk o alls, daytime sedation, and adverse cognitive e ect. Ideally, the lowest possible dose and shortest acting ormulations (ie, triazolam, temazepam, zaleplon, or zolpidem), should be used inpatient populations at risk o side e ects, including the elderly. Ramelteon (Rozerem) is a synthetic melatonin analogue. Ramelteon has demonstrated ef cacy in decreasing sleep latency, as well as increasing total sleep time, but does not cause drowsiness the next

60 y old

Sedation, orthostatic hypotension, hyperglycemia, ↑ appetite, ↑ weight, hyperlipidemia

The most sedating o the atypical antipsychotics, it is requently used as a sleep aid. Not recommended or insomnia or other sleep problems unless there is a comorbid psychiatric disorder. Dosed lower (25-100 mg) when used or insomnia vs or FDA-approved indications (600-800 mg) O atypical antipsychotics, olanzapine is the most likely to cause metabolic complications. Should not be used solely or insomnia Atypical antipsychotics should not be used in the elderly due to increased risk o death associated with atypicals. Haloperidol, a conventional antipsychotic can be given in low dose

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Olanzapine (Zyprexa) Haloperidol

Barbiturate Chloral hydrate

Sedation, hyperglycemia, ↑ appetite, ↑ weight, hyperlipidemia, prolonged QTc. Sedation, weight gain, prolonged QTc

Over sedation, respiratory depression, nausea, vomiting, diarrhea, drowsiness, ↓ cognitive unction, psychotic symptoms (paranoia, hallucinations), vertigo, dizziness, headache

E icacy as anxiolytic or >4 mo use not established. Not FDA-approved or insomnia. Avoid in patients >60 y old, closed-angle glaucoma, prostatic hypertrophy, severe asthma, and COPD

Chloral hydrate has been used or the short-term ( 40, with otherwise unexplained serum HCO3 > 27), as well as patients at risk or hypoventilation due to myopathy (especially myotonic dystrophy which can have a narcolepsy-like presentation), neuromuscular junction dys unction (myasthenia gravis), motor neuron disease, chest musculoskeletal de ormity (kyphosis, scoliosis), primary lung pathology (restrictive or obstructive pulmonary disease), or hepato-pulmonary or intrapulmonary le t to right shunts. 686

■ INPATIENT MANAGEMENT In patients with primary hypersomnia or EDS secondary to stroke or other etiologies, wake-promoting agents can be considered i inability to stay awake hinders the recovery and rehabilitation process. Sympathomimetics, including methylphenidate or Adderall, either immediate or sustained release, with 5 to 20 mg q4-6 hour or bid dosing respectively, maximum 60 mg total daily, may be a reasonable starting point (see Table 96-2). However, sympathomimetics, which raise not only the wake-promoting dopaminergic tone, but also a ect norepinephrine reuptake and release, can cause dose-dependent hypertension and tachycardia, and are thus relatively contraindicated in patients with coronary artery disease, hypertension, coronary vasospasm and seizures, as they can also lower the seizure threshold. Anxiety, headaches, insomnia, nausea and anorexia with weight loss include additional side e ects. Moda nil (Provigil) and armoda nil (Nuvigil) are not associated with hypertension and tachycardia, and are there ore pre erred in patients with cardiovascular comorbidities. Starting doses are 50 to 100 mg qday to bid (but no later than 2-3 PM to avoid insomnia), and can be up- titrated to 400 mg max daily dose or moda nil, or 300 mg max daily dose or Provigil. Headache, reduced oral contraceptive ef cacy and possibility o Stephens Johnson syndrome, as well as nausea and anxiety are possible side e ects. Noninvasive positive pressure ventilation (NPPV), starting with bilevel, improves sleep ef ciency, total sleep time, and quality o li e in patients with hypercapnic COPD without signi cantly improving gas exchange and should be considered as an adjunctive therapy or improving sleep and quality o li e in these patients. A rough bedside calibration o settings is usually per ormed by respiratory technicians, where expiratory positive airway pressure (EPAP) is titrated to resolution o obstructive breathing (snoring, inspiratory or expiratory grunting, apneas) which is typically worst during supine and REM sleep, and pressure support o 4 to 6 cm H2O above estimated EPAP can be used or ventilation purposes (ie, inspiratory positive airway pressure [IPAP] 10 to 12 cm over EPAP 6 cm. SLEEP-RELATED MOVEMENT DISORDERS

■ EVALUATION Patients with OSA, renal ailure, synucleopathies, and pregnant or anemic patients requently have concomitant RLS or PLMD, which are distinct problems and need to be di erentiated rom peripheral neuropathy and positional or nocturnal leg cramps. RLS is thought to a ect as much as 40% o the population and is characterized by a sensory-motor disturbance including unpleasant “creeping” or “crawling” sensation in the extremities or torso, with or without involuntary hyperkinetic movements during wake. A cardinal eature is the desire to move the a ected extremity, with symptoms relieved by movement. Symptoms classically have a circadian distribution, with onset or exacerbation in the late evening or be ore bedtime, o ten contributing to or causing sleep-onset insomnia. The requisite bed rest during hospitalization can worsen RLS, urther exacerbating sleep problems. The etiology o RLS is not completely understood, but it may relate to inadequate generation or transport o dopamine due to iron de ciency or iron metabolism disturbance.

■ INPATIENT MANAGEMENT Goal erritin in RLS patients is >75 µg/L. O note, erritin is an acute phase reactant and is likely to be alsely elevated during acute illness. There ore, not only serum erritin, but percent trans errin saturation and total iron-binding capacity (TIBC) should be evaluated. High dose iron supplementation should be initiated i hypoerritinemia ( erritin < 50 µg/L) or iron de ciency with trans errin saturation < 20% or TIBC > 400 µg /L is present.

SLEEP BEHAVIORS (PARASOMNIAS)

■ EVALUATION Nonrapid eye movement (NREM) sleep parasomnias, including conusional arousals, sleepwalking, and night terrors, are disorders o partial/incomplete arousal rom deep or slow wave (SWS, N3) sleep during the rst third o the night when SWS tends to occur. They are characterized by complex, seemingly purpose ul behavior without individual awareness and, in the case o night terrors, hyperarousal including diaphoresis, agitation, pupillary dilation, and ear ul behaviors. Unusual mani estations reported in the inpatient setting including patients repeatedly pulling out intravenous or central lines in their sleep, with anterograde amnesia or the event. Sleep disruption and deprivation and psychophysiological stress are requent risk actors. Overnight polysomnography may be required to rule out nocturnal seizures, but these are typically more stereotyped, o shorter duration, rarely result in leaving the bed, and are requently accompanied by bizarre hypermotoric movements (in the case o rontal lobe epilepsy) or ocal neurological signs and symptoms. REM parasomnias: patients with neurodegenerative disorders, especially synucleopathies including PD, MSA, and LBD and, to a lesser extent, tauopathies such as Alzheimer disease, have an increased risk o REM sleep behavior disorder (RBD), which requently precedes the motor mani estations o neurodegeneration by years to decades. RBD is characterized by dream enactment in

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the context o loss o typical muscle atonia during REM sleep. Upon awakening rom an episode o dream enactment patients clearly recall vivid and, in the case o men especially, requently violent dreams, with dream enactment such as punching, kicking, yelling, and sometimes launching themselves out o bed, corresponding to ghting, pursuit or eeing in the corresponding dream. SSRIs commonly unmask RBD, but untreated OSA and RLS/PLMS can also precipitate RBD.

l e e p D i s t u r b a n c e i n t h e H o s p i t a l i z e d P a t i e n

Good sleep hygiene with regular sleep-wake times and adequate sleep duration are important because sleep deprivation may trigger arousals. Ensuring the sa ety o the environment is essential or these patients. Waking up patient or the use o restraint should be avoided in NREM parasomnias, as con ronting patients could prolong the episode and may even worsen the behavior. Patient should be quietly guided back to bed. In the case o requent occurrence or injury to patient, pharmacologic therapy could be considered. Clonazepam 0.25 to 1 mg (commonly e ective at 0.5 mg) is generally e ective in both NREM and REM parasomnias, as it reduces both SWS and arousals. High dose melatonin (starting with 3 mg at bedtime, titrating up by 3 mg every 2-3 nights to max 12-15 mg at bedtime) is also an e ective alternative or RBD, but not NREM parasomnias. Clonidine has also been trialed as treatment. Selective serotonin receptor inhibitors (SSRIs) requently unmask RBD and i possible, use should be minimized. Sleep disturbance, or example rom untreated OSA or RLS/PLMS, should be minimized as it may lead to lower arousals threshold and requent sleep stage or sleep wake transitions also resulting in dream enactment.

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The equivalent o elemental iron 65 mg bid to tid dosing, with vitamin C or orange juice and avoidance o concurrent calcium supplements or alkaline dairy products or improved absorption is recommended. Various iron ormulations (the most common being errous sul ate 325 mg) exist, which may be substituted in cases o nausea or constipation, the two most common side e ects o iron supplementation. Ferritin and iron studies should be repeated in the outpatient setting, 3 to 4 months a ter initiation o supplementation. Intravenous dextran in usions can be considered as alternatives to oral supplementation in cases o intolerable side e ects or poor absorption. Dopamine (DA) agonists, namely ropinirole (Requip) 0.25 to 2 mg 30 to 60 minutes prior to onset o RLS symptoms, or pramipexole (Mirapex) 0.125 to 0.75 mg 2 to 3 hours prior to onset o symptoms, used to be considered rst line therapy (Table 96-2). However, high incidence o augmentation (or the earlier onset o more severe symptoms spreading to arms or torso), and side e ects including nausea, sedation or paradoxical insomnia, orthostasis and impulse control dysregulation with behaviors such as compulsive gambling, spending, and hypersexuality have, in many cases, displaced the DA agonists as rst line therapy. Double-blind controlled studies have showed similar to higher ef cacy and reduced or absent augmentation with α2δ calcium channel agonists, including pregabalin (Lyrica) and gabapentin (Neurontin), which are increasingly becoming rst line therapy or RLS, particularly in individuals with comorbid neuropathy, headaches or insomnia. Side e ects o the α2δ calcium channel agonists include sedation, weight gain, and orthostasis, as well as rebound anxiety. Opiates, including methadone (typically in the 5-25 mg qhs range) and oxycodone (on average 25 mg total daily dose, tailored to timing o worst symptoms), are very e ective in the treatment o RLS, and while it is a theoretical worry, incidence o dependence and abuse in RLS patients is low. Clonidine and long acting benzodiazepines, such as clonazepam, can be considered as well in re ractory cases. Selective serotonin uptake inhibitors (SSRIs), tricyclic antidepressants (TCAs), antihistamine agents, and alcohol may exacerbate RLS and should be avoided, i possible. Buproprion (Wellbutrin) is the one antidepressant which does not appear to exacerbate RLS.

SLEEP AND PSYCHIATRIC DISTURBANCE

■ EVALUATION Sleep disturbance is a diagnostic criterion or mood, anxiety, substance abuse, and psychotic disorders. Thus, comorbid psychiatric disorders must be considered in hospitalized patients with sleep complaints, even i not previously diagnosed. Major depression is particularly common in hospitalized patients with early morning insomnia. Longitudinal studies have ound that prior insomnia was associated with 2- to 5- old increase in the odds o mood and anxiety disorders and suicide. O ten, sleep disorders precede the onset o clinical depression, supporting the importance o assessing patient sleep quality during hospitalization.

■ INPATIENT MANAGEMENT Traditionally, treatment o underlying mood disorder or anxiety has been prioritized temporally prior to treatment targeting comorbid insomnia speci cally. However, it is increasingly recognized that pharmacological and nonpharmacological treatment o insomnia is synergistic to treatment o mood or anxiety disorders, and lower the likelihood o depressive episode recurrence. This growing recognition is paralleled by a body o research suggestive that insomnia is indeed a state o hyperarousal, with brain overactivation evident in unctional brain imaging in insomniacs compared to “normals.” While comprehensive cognitive behavioral therapy or insomnia (CBT-I) can be pursued in the outpatient setting, pharmacological therapy should be considered in the inpatient setting, tailored to patient comorbidities and medication pharmacokinetics (see Table 96-6). Several hypnotics commonly used in comorbid anxiety/depression merit mention, including eszopiclone (lunesta), a long-acting hypnotic with action on the α2 and 3 subunits o the GABAA receptor, thus mild antianxiety e ects in addition to hypnotic e ects; doxepin (silenor), a tricyclic antidepressant used or insomnia at 3 to 6 mg, doses much lower than doses used in 687

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management o depression; mirtazapine (Remeron), a norepinephrine and serotonin speci c antidepressant, has hypnotic e ect at lower doses (7.5-15 mg at bedtime), which resolve at the higher doses used or depression (30 mg and higher); trazodone (desyrel), a tetracyclic antidepressant, had dual hypnotic and antianxiety properties; venla axine (E exor), a serotonin-norepinephrine reuptake inhibitor (SNRI), has been validated or perimenopausal hot ashes and associated sleep disturbance despite its overall activating rather than sedating properties.

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1. Poor per ormance o ADLs heralds a “red ag” or increased sleep disturbance during hospitalization. 2. There is an increasing recognition that primary insomnia represents a hypermetabolic, hyperactivated state, suggesting the value o at least short term pharmacological management when nonpharmacological interventions are insuf cient. Avoid abrupt discontinuation o hypnotics, sedatives and pain medications i possible to avoid rebound insomnia. 3. Maintain high level o clinical suspicion or sel -medication as the etiology o alcohol ( or comorbid chronic insomnia, mood or anxiety disorders) or nicotine ( or excessive daytime sleepiness/ atigue) use disorders.

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PRACTICE POINT: CIRCADIAN MISMATCH IN THE HOSPITALIZED PATIENT 1. Clinicians should suspect circadian misalignment as a common etiology o sleep initiation insomnia in elderly patients with or without dementia, especially Alzheimer tauopathy, TBI/postconcussive syndrome, hepatic cirrhosis, congenital blindness, or adolescents. Recognize importance o behavioral measures, including restriction o time in bed, consistent wake times, avoidance or minimization o daytime naps, light/dark, and physical activity cues, and low-dose melatonin approximately 12 hours prior to daily wake time as chronoagent or sleep timing/circadian phase adjustment and sleep consolidation. 2. Low-dose (0.3-3 mg) melatonin administered 2 to 3 hours prior to desired bedtime, is typically more e ective as a chronoagent, and typically minimally e ective as a hypnotic, with doses as high as 5 mg or greater not currently indicated. 3. Recognize that timing o light exposure is critical in manipulation o the sleep zone—in patients with delayed circadian phase (“night owls”) early morning light exposure may precede the body temperature nadir. and may thus urther delay the sleep phase. PRACTICE POINT: SLEEP DISORDERED BREATHING IN THE HOSPITALIZED PATIENT 1. It is a common error to assume that lack o desaturation below 90% on nocturnal oximetry “rules out” sleep apnea. In act recurrent desaturations, even i above the 90% threshold, have long term adverse oxidative damage and sympathoactivation consequences. In act, some patients with severe sleep apnea with requency o obstructive respiratory events or apnea hypopnea index (AHI) >30 or as high as 100/hour, may never exhibit desaturation below the low 90s due to rapid cycling o respiratory events (desaturation “banding” rather than “umbrella desaturations” may be seen in those patients, but inpatient oximetry requently does not have the resolution to allow or recognition o this pattern). 2. Have a high index o suspicion or obesity hypoventilation syndrome in hypersomnolent morbidly obese patients (BMI > 40)

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and otherwise unexplained serum HCO3 > 37, with or without associated sleep disordered breathing or hypoxemia. PRACTICE POINT: SLEEP-RELATED MOTOR ACTIVATION 1. Have a high index o suspicion or RLS/PLMD contribution to sleep initiation, and maintenance insomnia should be sustained in patients with renal disease, pregnant patients, PD/MSA/LBD patients, patients with acute blood loss or anemia, and (post-op) patients on rapid opiate tapers (at risk o rebound RLS). DISCHARGE CHECKLIST 1. Re erral to sleep specialist has been considered or the patient with insomnia and at risk o OSA, hypoventilation, circadian mismatch, RLS/PLMD. 2. Re erral to psychiatric specialist has been considered or the patient with insomnia and at risk or mood or anxiety disorder, including patients with substance use disorders. 3. Re erral to neurology specialist has been considered or the patient with dream enactment behavior consistent with RBD and/or parkinsonian eatures (orthostasis, hyposmia, masked acies, psychomotor slowing or rank bradykinesia, tremor, rigidity). 4. A plan is in place or repeat check o erritin and iron studies in RLS/PLMS patients ollowing normalization o illness (and thus possibly alsely elevated erritin levels given acute phase reactant properties) and/or 3 to 4 months ollowing initiation o high dose oral iron supplementation.

SUGGESTED READINGS Benca R. Clinical evaluation o sleep disorders. In: Sleep Disorders: The Clinician’s Guide to Diagnosis and Management. New York, NY: Ox ord University Press; 2012: 25-46. Cundrle I, Calvin AD, Somers VK. Sleep deprivation and the cardiovascular system. In: Bianchi MT, ed. Sleep Deprivation and Disease. New York, NY: Springer; 2014: 131-148. Fava M, et al. Eszopiclone co-administered with uoxetine in patients with insomnia coexisting with major depressive disorder. Biol Psychiatry. 2006;59(11):1052. Gillis CM, et al. Inpatient pharmacological sleep aid utilization is common at a tertiary medical center. J Hosp Med. 2014;9(10):652. Goldstein C. Management o Restless Legs Syndrome/Willis-Ekbom Disease in hospitalized and perioperative patients. Sleep Med Clin. 2015;10(3):303. Mignot EJ. A practical guide to the therapy o narcolepsy and hypersomnia syndromes. Neurotherapeutics. 2012;9(4):739. Schutte-Rodin S, et al. Clinical guideline or the evaluation and management o chronic insomnia in adults. J Clin Sleep Med. 2008;4(5):487. Unbehaun T, et al. Management o insomnia: update and new approaches. Nat Sci Sleep. 2010;2:127. Young JS, et al. Sleep in hospitalized medical patients. Part 1. Factors a ecting sleep. J Hosp Med. 2008;3(6):473. ACKNOWLEDGMENT Some o the material in this chapter was adapted rom the previous edition chapter authored by Kimberly A. Hardin, MD, MS, FAASM, Kristina Antonson, MD, PhD, Anne B. McBride, MD, and Julie S. Young, MD, MS.

97

CHAP TER

Nausea and Vomiting John O. Clarke, MD Susan Y. Quan, MD

Key Clinical Questions 1

What key clinical entities must be considered in the initial assessment o a hospitalized patient with acute nausea and vomiting?

2

What is the clinical diagnostic approach to the inpatient with nausea and vomiting?

3

How should patients with nausea and vomiting in the hospital setting be treated?

CASE 97-1 A 28-year-old woman was admitted rom clinic with re ractory nausea and vomiting. She has a history o long standing type 1 diabetes mellitus, which has been complicated by retinopathy and neuropathy. From a gastrointestinal standpoint, symptoms began 3 years ago with the onset o early satiety, nausea, and vomiting. This has progressively worsened despite decent glycemic control and aggressive li estyle modi cation. She reports constant nausea, which is worse with ood, but present to some extent even i she has had nothing to eat. She also reports vomiting a ter most meals—this may be as soon as minutes a ter eating or as long as hours. Symptoms are present with both liquids and solids and may even be worse with liquid intake. She is taking ondansetron every 8 hours and promethazine as needed in between ondansetron doses. She has attempted therapy with metoclopramide in the past but did not eel any improvement and also developed a tremor (which reversed upon stopping metoclopramide). She had an attempted solid gastric emptying study but vomited the eggs shortly a ter ingestion. Her liquid emptying study was markedly abnormal. Prior endoscopy showed no evidence o gastritis, peptic ulcer disease, or gastric outlet obstruction. An upper gastrointestinal (GI) series with small bowel ollow-through showed delayed gastric emptying, no abnormal distention, and apparently normal small bowel transit. She has now lost 70 pounds over the past year and was admitted or evaluation, rehydration, and urther management.

INTRODUCTION Nausea and vomiting are common and uncom ortable symptoms with a large number o underlying causes. Nausea is a subjective sensation, usually experienced in the epigastrium or throat when vomiting is imminent (although vomiting may or may not occur). Nausea may be ollowed by retching, which is repetitive active contraction o the abdominal musculature. Retching may occur in isolation without the orce ul expulsion o gastric contents. In contrast, vomiting is a highly physical event that results in the evacuation o gastric contents. This should be distinguished rom regurgitation, which is the e ortless re ux o gastric or esophageal contents to the hypopharynx.

■ PATHOPHYSIOLOGY Studies have suggested that the act o vomiting is controlled by a central neurologic center. Borison and colleagues have studied the mechanism o vomiting in cats and ound that vomiting can be induced by electrical stimulation o a “vomiting center” located in the dorsal portion o the medulla. These studies, however, have not been repeated in human subjects. Experimental studies have also suggested that a chemoreceptor trigger zone (CTZ) activates the vomiting center when stimulated. Emetic stimuli can cause vomiting by one o two mechanisms. One mechanism is by activation o a erent vagal and sympathetic neural pathways within the gastrointestinal tract that act directly on the vomiting center. Ablation o these pathways in experimental animals prevents vomiting induced by copper sul ate, which is known to cause vomiting. The second mechanism by which emetic stimuli can cause vomiting is via the CTZ. Unlike the vomiting center, 689

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the CTZ is not responsive to electrical stimuli, but only to chemical stimuli rom the circulation that crosses the blood-brain barrier. These stimuli include drugs, uremia, diabetic ketoacidosis, and toxins derived rom gram-positive bacteria. The exact neurotransmitters that are involved are not known, but there is strong evidence that both dopamine and serotonin may mediate vomiting—hence explaining their role in pharmacologic treatment o nausea and vomiting. Regardless o the emetic stimulus or the mechanism by which the vomiting center is activated, the act o vomiting is initiated rom the vomiting center. The e erent pathways are primarily somatic and involve the vagus, phrenic, and spinal nerves that supply the abdominal musculature.

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There are a vast number o causes o nausea and vomiting (Tab le s 97-1 and 97-2). The di erential diagnosis can be approached with a care ul history and physical examination. The acuity o symptoms should rst be addressed. Acute nausea and vomiting are usually associated with acute in ection (especially o the gastrointestinal tract), ingestion o toxins, gastrointestinal obstruction or ischemia, new medication, pregnancy, or head trauma/increased intracranial pressure. Chronic nausea and vomiting, which are usually de ned as the persistence o symptoms or more than 1 month, suggest partial mechanical obstruction, intracranial pathology, dysmotility such as gastroparesis, metabolic or endocrine etiology, or a psychologic disturbance. The timing o vomiting in relation to meals can also be important in elucidating the etiology o symptoms. Patients with a pyloric peptic ulcer or psychogenic vomiting may present with vomiting during or soon a ter a meal. Patients with gastric outlet obstruction as in diabetic or postvagotomy gastroparesis are more likely to experience delayed vomiting o more than 1 hour a ter eating. The content o the vomitus can urther provide important in ormation. Old ood in the vomitus may suggest gastroparesis, gastric outlet obstruction, or a proximal small bowel obstruction, while presence o bile indicates patency between the stomach and proximal duodenum. The physical examination may be help ul in determining the underlying etiology and is important in assessing the consequences o nausea and vomiting. The general examination can detect important ndings such as tachycardia or orthostatic hypotension, which would suggest dehydration. Examination may also reveal jaundice, abdominal masses, or eatures suggestive o an endocrine process such as thyrotoxicosis or Addison disease. Abdominal examination should ocus on presence or absence o bowel sounds, tenderness, distention, as well as evidence o masses, hernias, or prior surgical procedures. The history and physical examination should direct which lab tests and radiologic studies to order. Basic laboratory testing includes a complete blood count and electrolyte panel. Sustained vomiting resulting in loss o water and electrolytes may lead to dehydration and a hypokalemic metabolic alkalosis. In women, a pregnancy test should be obtained not only to determine i pregnancy is the cause o vomiting, but also as a prerequisite or any radiologic studies. Further laboratory testing may include serum drug levels in patients who are taking certain medications, as well as thyroid unction tests. 690

TABLE 97-1 Differential Diagnosis of Nausea and Vomiting Abdominal Causes Mechanical obstruction Gastric outlet obstruction Small bowel obstruction Motility disorders Chronic intestinal pseudo-obstruction Functional dyspepsia Gastroparesis Irritable bowel syndrome Organic disorders Acute appendicitis Acute cholecystitis Acute hepatitis Crohn’s disease In lammatory intraperitoneal disease Mesenteric ischemia Mucosal metastases Pancreatic cancer Pancreatitis Peptic ulcer disease Retroperitoneal ibrosis Drugs (see Table 97-2) Infectious Causes Acute gastroenteritis Bacterial Viral Nongastrointestinal in ectious Otitis media Systemic Metabolic and Endocrine Causes Acute intermittent porphyria Addison disease Diabetes mellitus Hypercalcemia Hyperparathyroidism Hyperthyroidism Hyponatremia Hypoparathyroidism Pregnancy Uremia

Nervous System Causes Autonomic system disorders Demyelinating disorders Hydrocephalus Congenital mal ormations High intracranial pressure Low-pressure hydrocephalus Intracerebral lesions with edema Labyrinthine disorders Labyrinthitis Meniere disease Motion sickness Meningitis Migraine headaches Seizure disorders Visceral neuropathy Other Causes Alcohol abuse Anxiety and depression Cardiac disease Congestive heart ailure Myocardial ischemia Radio requency ablation Cyclic vomiting syndrome Eating disorders Functional disorders Hypervitaminosis A Intense pain Paraneoplastic syndrome Postoperative state Postvagotomy Radiation therapy Rheumatologic disorders Scleroderma Sjögren’s syndrome Systemic lupus erythematosis Rumination syndrome Starvation

Flat radiographs o the abdomen or a computed tomographic (CT) scan may reveal mechanical obstruction. An upper gastrointestinal series or endoscopy is particularly help ul in making the diagnosis when the history and physical examination suggest that peptic ulcer disease or gastric outlet obstruction is likely. It is important to recognize that the serial imaging included with an upper GI series adds important diagnostic in ormation that a single image obtained during a CT scan may not. The absence o obvious obstructive pathology on

Tamoxi en Vinblastine

a CT scan should not dissuade the clinician rom obtaining an upper GI series or small bowel ollow-through i appropriate. In patients with chronic nausea and vomiting who have a normal upper gastrointestinal series and endoscopy, urther evaluation with a radionuclide gastric emptying study can be considered. Electrogastrography and antroduodenal manometry can also be considered i available; however, the clinical utility o these studies in most patients with chronic nausea is not well established, and these procedures are o ered at only select tertiary acilities. In patients with normal gastric emptying and motility studies, evaluation with CT, ultrasonography or biliary scintigraphy may provide valuable in ormation i a gallbladder, pancreatic, or hepatobiliary etiology is suspected. In addition, given that central nervous system processes can result in nausea, one should have a low threshold to per orm neurologic imaging in the appropriate clinical context. Finally, a psychiatric consultation should also be considered i studies do not indicate any organic pathology. When vomiting arises in the hospital, o ten it is medications that are to blame. Opiates, in particular, slow gastrointestinal transit and have additional direct emetogenic e ects in some patients. Chemotherapeutic medications, antibiotics, and general anesthesia are also common precipitants o nausea in hospitalized patients. Abdominal procedures are also well known to result in nausea and delayed gut motility, independent o the anesthesia received. In many instances in which a clear precipitant is apparent, there is not a need to pursue aggressive diagnostic interventions; supportive care is adequate. However, i the symptoms are out o proportion to the clinical scenario or unusually prolonged (eg, persistent nausea and vomiting 4 days a ter general anesthesia or a nonabdominal procedure), diagnostic evaluation is wise. Additionally, other signs and symptoms such as ever or ocal neurologic de cits should be sought out, and i present, should lead to prompt diagnostic evaluation. Finally, myocardial ischemia (particularly right-sided myocardial in arction) should be considered in hospitalized patients with cardiovascular risk actors. Diaphoresis, dyspnea, and changes in heart rate or blood pressure may suggest a cardiac etiology.

C H A P T E R 9 7 N a u s e a a n d V o m

Treatment o nausea and vomiting involves correction o uid and electrolyte imbalance i present, identi cation and treatment o the underlying cause i one exists, and relie o symptoms either by suppression or by elimination i the primary cause cannot be promptly identi ed and removed. Patients with long-standing chronic nausea and vomiting are at risk or developing malnutrition, and it is important to monitor or this in the hospital setting. I a patient is not able to tolerate adequate oral caloric intake a ter a 5-day period, consideration should be given or enteral or parenteral eeding. Enteral eeding is usually the rst option; however, dislodgment o enteral eeds with acute vomiting is not uncommon and occasionally parenteral eeding may be required.

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In many instances in which a clear precipitant is apparent, there is no need to pursue aggressive diagnostic interventions; supportive care is adequate. However, i the symptoms are out o proportion to the clinical scenario or unusually prolonged (eg, persistent nausea and vomiting 4 days a ter general anesthesia or a nonabdominal procedure), diagnostic evaluation is wise.

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Cardiovascular Drugs Antiarrhythmics Antihypertensives β-Blockers Calcium channel antagonists Digoxin Central nervous system drugs Antiparkinsonian drugs Anticonvulsants Diuretics Gastrointestinal medications Azathioprine Lubiprostone Sul asalazine Narcotics Nicotine Nonsteroidal antiin lammatory drugs Oral contraceptives Theophylline

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TABLE 97-2 Common Medications Associated with Nausea and Vomiting

Pharmacologic treatment There are many commonly employed antiemetic agents, and these medications can be divided into two main categories: central antiemetic agents and peripheral prokinetic agents. In practice, many drugs employ both mechanisms and many o the speci c pathways by which these medications exert bene t are still being elucidated. The main antiemetics are detailed in the next sections. Dopamine D2 receptor antagonists Metoclopramide is the classic agent in this category and exerts a central antiemetic e ect through antagonism o dopamine D2 receptors as well as a peripheral prokinetic e ect through stimulation o peripheral 5-HT4 receptors. Common indications include postoperative nausea and vomiting, chemotherapy and radiation therapy-induced nausea, and gastroparesis. The standard dose is 5 to 10 mg orally or intravenously three to our times daily. Metoclopramide is associated with signi cant side e ects, including restlessness, anxiety, somnolence, extrapyramidal e ects, QT interval prolongation, and, i used or a prolonged period o time, tardive dyskinesia in rare cases (which in some cases is irreversible). Metoclopramide is currently the only US Food and Drug Administration (FDA)-approved medication or diabetic gastroparesis; however, due to side e ects it has a black box warning against use o greater than 12 weeks based on the risk o tardive dyskinesia. Domperidone is a second agent in this category that crosses the blood-brain barrier poorly and is believed to act primarily through prokinetic unction as a peripheral D2 receptor antagonist. Domperidone is a weaker antiemetic than metoclopramide, but as it is better tolerated, higher doses can be employed and the risk o anxiety and dystonia is signi cantly reduced. Domperidone is not approved or use in the United States; however, it can be obtained by ling an investigational new drug application with the FDA. Recent studies suggest QT prolongation and a potential increase in the risk o sudden cardiac death and i this is used clinically then close monitoring is essential. Phenothiazines Phenothiazines (chlorpromazine, promethazine) block D2 dopaminergic receptors in addition to muscarinic M1 receptors and histamine H1 receptors. These drugs induce relaxation and somnolence 691

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and are generally used parenterally or as suppositories in patients with acute intense vomiting o central origin (such as with migraine headaches and motion sickness). Although e ective, side e ects can be signi cant and o ten limit use. O note, promethazine does have a black box warning rom the FDA due to severe tissue injury; as a vesicant, i promethazine extravasates into subcutaneous tissues or is accidentally in used intra-arterially, severe local necrosis may occur. Butyrophenones

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Butyrophenones block D2 dopaminergic receptors and muscarinic M1 receptors and are believed to a ect nausea through central antiemetic e ects. Commonly used agents in this category include droperidol and haloperidol. As with the phenothiazines already mentioned, side e ects and sa ety concerns have limited routine use o these agents, although they may be o bene t on an adjunct basis.

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These agents work primarily through blockage o histamine H1 receptors and muscarinic M1 receptors at a central level. Commonly used antihistamines are diphenhydramine, meclizine, and cyclizine. The most commonly used antimuscarinic agent is scopolamine. In addition, promethazine also has both antihistamine and antimuscarinic e ects. Somnolence and drowsiness are the main limiting actors with these agents; however, anticholinergic e ects can also be problematic—particularly or older patients. These agents are commonly used or treatment o motion sickness and nausea associated with vestibular disease. Serotonin antagonists Serotonin 5-HT3 receptors seem to play a key role in nausea, and selective antagonists (such as ondansetron) are particularly e ective through central nausea mediation. In addition, these agents may have a mild gastric prokinetic unction. These agents are primarily used or postoperative nausea and a ter chemotherapy and radiation therapy; however, given their ef cacy they are o ten used or re ractory nausea related to other conditions. O note, headache is a common side e ect. For those patients that cannot tolerate oral agents, granisetron is available in transdermal orm with a 7-day duration o action.

is also used to clear the stomach o retained ood and blood prior to endoscopy. Erythromycin is best used acutely and is, un ortunately, not a good agent or chronic use in most patients as it is associated with tachyphylaxis. Erythromycin also induces nausea in a signi cant subset o patients and is associated with QT interval prolongation. New synthetic motilin agonists devoid o antibacterial activity are in development; however, none are ready or clinical use at the present time. Ghrelin is a peptic structurally similar to motilin that also accelerates gastric emptying. Ghrelin receptor agonists are under development and may play a role in the uture; however, they are not available at present or clinical use. Glucocorticoids The antiemetic mechanism o glucocorticoids is not clear and numerous hypotheses have been raised, including inhibition o central prostaglandin synthesis, altered serotonin processing, and enhanced endorphin release. Regardless, glucocorticoids do appear to have an antiemetic e ect and are o ten used or postoperative nausea or or treatment o nausea in the context o chemotherapy or radiation. In most cases, this use is as an adjunct therapy in combination with other agents rather than as a sole treatment modality. Cannabinoids Synthetic cannabinoids have entered the therapeutic armamentarium or treatment o nausea. Two oral ormulations, dronabinol and nabilone, are approved by the FDA or chemotherapy-induced nausea and vomiting re ractory to conventional antiemetic therapy. While attractive to many patients, use o these agents is o ten limited by hypotension and psychotropic reactions. Marijuana has also been used or treatment o chronic nausea; however, data and availability are limited and it is uncertain where this alls at present in the treatment algorithm. Neurokinin 1 receptor antagonists Neurokinin-1 (NK) receptor antagonists inhibit substance P/NK-1 and are potent antiemetics. These agents (aprepitant, osaprepitant) appear to be particularly e ective or treatment o postoperative vomiting and may be used as adjunct therapy or patients not responding to the oregoing measures. An ongoing large multicenter randomized trial is currently in progress evaluating the role o aprepitant in chronic nausea related to gastroparesis.

Serotonin agonists Serotonin 5-HT4 receptors seem to play a key role in gastric motility, and agonists o these receptors (such as metoclopramide, cisapride, and tegaserod) have signi cant prokinetic capabilities. O these agents, cisapride has the most potent unction and demonstrated ef cacy or nausea associated with gastroparesis, pseudoobstruction, or other motility cause; however, cisapride was removed rom the market due to QT-prolongation complicated by the risk o lethal ventricular arrhythmias. Tegaserod was also removed rom the market due to increased associated cardiac events. At the moment, the only medication available in the United States that works through this mechanism is believed to be metoclopramide, and, as detailed earlier, this is but one mechanism by which metoclopramide is believed to exert bene t. Prucalopride has been approved in Europe and Canada, but is not yet available in the United States. Motilin receptor agonists The classic motilin receptor agonist is the antibiotic erythromycin, which acts as a motilin receptor ligand on smooth muscle cells and enteric nerves, increasing gastric and intestinal peristaltic motor activity. In clinical practice, erythromycin may be used to treat acute nausea and vomiting associated with delayed gastric emptying and 692

Benzodiazepines Although not proven nor approved as therapy or nausea, anecdotal experience supports the use o benzodiazepines in patients with re ractory nausea, particularly when there appears to be a psychological or anticipatory component (ie, the patient reports nausea at the smell or sight o ood prior to ingestion). Alternative and surgical treatment For patients with re ractory nausea despite the pharmacologic options already detailed, it is occasionally necessary to explore alternative and surgical options. Acupuncture has been studied or treatment o nausea in select clinical situations and has shown bene t. Gastric electrical stimulation has also been explored or chronic nausea associated with gastroparesis. The concept is that an implantable neurostimulator delivers brie , low-energy impulses to the stomach, which alters a erent sensation, particularly with regard to nausea. This is approved or humanitarian use by the FDA; however, the procedure is not without risk, and clinical improvement is not universal—with most studies suggesting approximately a 40% response rate. At the moment, this is only approved or chronic nausea in the context o gastroparesis; however, studies are

CONCLUSION Nausea and vomiting are common in hospitalized patients and can occur due to a wide variety o causes. The initial step should be identi ying whether the symptoms are acute or chronic. I acute, the di erential diagnosis is somewhat more limited, and it is important to

Hasler WL, Chey WD. Nausea and vomiting. Gastroenterology. 2003;125:1860-1867.

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Chepyala P, Olden KW. Nausea and vomiting. Curr Treat Options Gastroenterol. 2008;5:202-208.

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Carlisle JB, Stevenson CA. Drugs or preventing postoperative nausea and vomiting. Cochrane Database Syst Rev. 2006;(3): CD004125.

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The patient was admitted or intravenous uids and started on erythromycin, while being continued on the remainder o her regimen. She declined supplemental enteral or parenteral nutrition and a ter stabilization was discharged home. As an outpatient she was started on domperidone and seen in consultation by surgery or gastric stimulator placement, which she underwent later that year. Following gastric stimulator placement, she had a di cult postoperative recovery period and was discharged home on parenteral nutrition, which she was able to eventually taper of . She did well or a period o 3 months with marked improvement in nausea and signi cant weight gain, but un ortunately developed recurrent debilitating nausea and progressive weight loss, leading to a jejunal tube placement or enteral nutrition. At present, nausea remains a signi cant ongoing issue despite the ef orts detailed here.

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CASE 97-1 (continued)

exclude li e-threatening issues that require emergent action (shock, hypokalemia, per oration, cerebral edema, organ in arction, poisoning), and pregnancy. I chronic, the di erential diagnosis is quite broad; however, by evaluating the patient’s history, examination, and basic test results it is o ten possible to arrive at the etiology. The best treatment is removal o the causative actor. I this is not possible, then there is a wide array o treatment options available rom a pharmacologic standpoint to at least ameliorate the symptoms. The choice o which pharmacologic agent to use is an individual decision based on the suspected etiology o nausea and concern or side e ects.

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ongoing that may broaden this indication. Other surgical options or chronic nausea do not appear to have suf cient data to pursue urther at the present time, except or perhaps completion gastrectomy in patients with nausea in the context o postsurgical gastroparesis—and potentially pyloroplasty in patients with gastroparesis and pylorospasm.

Lacy BE. Neuroenteric stimulation or gastroparesis. Curr Treat Options Gastroenterol. 2015; 13:409-417. Malagelada J, Malagelada C. Nausea and Vomiting. Sleisenger and Fordtran’s Gastrointestinal and Liver Disease, 10th ed. Philadelphia, PA: Saunders Elsevier; 2015:207-220. Matthews A, Haas DM, O’Mathuna DP, Dowswell T. Interventions or nausea and vomiting in early pregnancy. Cochrane Database Syst Rev. 2015;(9):CD007575. Quigley EM, Hasler WL, Parkman HP. AGA technical review on nausea and vomiting. Gastroenterology. 2001;120:263-286.

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CHAP TER

Numbness: A Localization-Based Approach

INTRODUCTION Patients may use the word numbness to describe an alteration in sensation (ie, paresthesia or sensory loss), strength (ie, weakness), or coordination (ie, clumsiness). There ore, the approach to the patient presenting with numbness begins with clari ying what the patient means by the word. This chapter will ocus on the evaluation o the patient with alteration in sensation. Di erential diagnosis in neurology requires determining the localization o the problem within the nervous system (brain, brainstem, spinal cord, nerve roots, peripheral nerves, neuromuscular junction, or muscle), the time course over which the problem has arisen (acute, subacute, or chronic), and any associated symptoms that accompany the chie complaint (eg, i the chie complaint is numbness, is there associated weakness or pain?). OVERVIEW OF SENSORY PATHWAYS (FIGURE 98-1)

Aaron L. Berkowitz, MD, PhD

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Sensory in ormation rom the body travels in peripheral nerves to dorsal root ganglia, then enters the spinal cord through the dorsal roots. A ter entering the spinal cord, di erent types o sensory in ormation travel in di erent pathways en route to the brain. Pain and temperature sensation travel in the spinothalamic (anterolateral) tracts, whereas proprioception and vibration travel in the dorsal (posterior) columns. Light touch sensation travels to some extent in both pathways and is there ore o less precise localizing value. The bers destined or the spinothalamic tracts cross directly to the contralateral anterolateral spinal cord a ter entering the spinal cord, and ascend through the brainstem to the thalamus, and rom the thalamus to the somatosensory cortex housed in the postcentral gyrus. A unilateral spinal cord lesion a ecting the spinothalamic tract at any level there ore causes contralateral loss o pain and temperature below the level o the lesion. Since the entering bers cross over several spinal levels, i this pathway is a ected in the spinal cord, there may also be a small patch o ipsilateral sensory loss at and above the level o the lesion. The dorsal column pathways remain ipsilateral in the spinal cord and cross at the level o the lower brainstem (the medulla), where it then ascends to the thalamus en route to the somatosensory cortex like the spinothalamic tract. There ore, a unilateral spinal cord lesion a ecting the dorsal column pathway causes ipsilateral loss o proprioception and vibration sensation below the level o the lesion, whereas a lesion superior to the medulla causes contralateral loss o proprioception and vibration sense. Sensation on the ace is subserved by the trigeminal nerves (cranial nerve V), which transmits in ormation to the brainstem, where it ultimately crosses to join the corresponding somatosensory pathways rom the body (ie, in ormation rom the le t trigeminal nerve crosses to the right side o the brainstem to join the alreadycrossed ascending sensory pathways rom the le t side o the body). All sensory in ormation rom the extremities and torso in both the spinothalamic and posterior column pathways is transmitted to the ventral posterior lateral (VPL) nucleus o the thalamus. Sensory in ormation rom the ace is represented in the ventral posterior medial (VPM) nucleus o the thalamus. Somatosensory in ormation rom these thalamic somatosensory nuclei is transmitted to the somatosensory cortex in the postcentral gyrus o the parietal lobe, with the ace represented on the lateral cortical sur ace, the lowerextremity superio-medially, and the upper extremity between these two regions.

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Figure 98 1 Dorsal columns, spinothalamic tracts, and basic trigeminal pathway.

LOCALIZATION OF SENSORY DISTURBANCES Alterations in sensation may be localized to one or more peripheral nerves, dorsal root ganglia, one or more nerve roots, the spinal cord, the brainstem, or the brain (and within in the brain, in the thalamus, somatosensory cortex, or the subcortical white matter that connects them). Clinical localization may be determined rom the pattern o sensory symptoms. Each level o the nervous system may be a ected by distinct pathological processes, distinguished by the time course o onset and progression o symptoms, as well as any associated symptoms and signs. For example, sudden-onset hemi-body numbness is highly suggestive o an ischemic in arct or intracerebral hemorrhage, whereas insidious onset o the same symptoms may suggest an intracranial tumor. Rapid development o sensory disturbances a ecting the distal bilateral lower extremities could signi y early Guillain-Barré syndrome or transverse myelitis, whereas similar symptoms o chronic onset could suggest a polyneuropathy due to systemic illness or a spinal tumor.

■ PATTERNS OF SYMPTOMS (FIGURE 98-2) Overview Mononeuropathy and radiculopathy lead to sensory loss in a speci c distribution, which may be accompanied by a pattern o weakness

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or re ex loss related to the nerve or root a ected. Polyneuropathy leads to symmetric symptoms that o ten begin distally, leading to the ‘stocking-glove’ pattern. There are several patterns o sensory symptoms that can occur rom spinal cord lesions, depending on whether the lesion is a complete transection, unilateral (BrownSequard syndrome), central (e.g., syrinx), anterior, or posterior (see below). Thalamic, subcortical, or cortical lesions cause contralateral sensory loss that may be complete (causing a hemisensory de ect) or may a ect only part o the contralateral body depending on the size and location o the lesion within these structures. A common pattern o sensory disturbance due to a unilateral brain lesion is a sensory disturbance a ecting the contralateral ace and hand, since these are the most highly represented regions o the body, and also since their representations are adjacent and both within the middle cerebral artery territory in the somatosensory cortex. Although it is possible to develop isolated sensory symptoms rom a very small well-placed brainstem lesion, this is uncommon in practice. Given the large number o structures in a small anatomical region (eg, cranial nerve nuclei, descending motor pathways, connections between the brainstem and cerebellum), other neurologic eatures generally predominate over sensory symptoms and signs with brainstem lesions. A distribution o sensory symptoms that is unique to the lower brainstem is the presence o “crossed ndings”—unilateral acial sensory disturbance with contralateral sensory disturbance in the rest o the body. I the ace is a ected, this requires a lesion in the trigeminal nerve, the brainstem, or the cerebral hemispheres, whereas de cits in the arm(s) and/or leg(s) can localize anywhere along the neuraxis.

Neuropathy re ers to pathology o one or more peripheral nerves. Symptoms depend on the ber type a ected and can there ore be sensory, motor, autonomic, or a combination o these. Sensory symptoms may include negative symptoms (ie, loss o sensation), positive symptoms (eg, paresthesias, pain), or both. Sensory loss can be multimodal or may be speci c to pain/temperature or vibration/ proprioception, depending on the ber type(s) a ected. Mononeuropathy. When a single nerve is a ected, symptoms occur in the distribution o that particular nerve. These symptoms may involve sensory disturbances and/or weakness depending on whether the a ected nerve is sensory, motor, or mixed, and the degree to which the nerve is a ected. Mononeuropathies are most commonly caused by trauma or compression, and patients with underlying polyneuropathy (eg, due to diabetes) can be predisposed to superimposed mononeuropathies. The most common mononeuropathy is carpal tunnel syndrome, in which the median nerve is compressed in the carpal tunnel, leading to sensory symptoms on the lateral palm sparing the medial and posterior sur ace, o ten with associated weakness o thumb abduction. Mononeuropathy can be dif cult to distinguish clinically rom radiculopathy, although radiating pain rom the neck or back is more typical o radiculopathy. Although numbness in the distribution o a single nerve (eg, carpal tunnel syndrome) is more commonly seen in the outpatient setting, the hospitalist should be aware o mononeuropathies that may arise in hospitalized patients. Focal numbness, weakness, and/or pain can develop postoperatively due to operative positioning leading to nerve compression or due to injury rom retractors (eg, the emoral nerve in pelvic surgery). Unilateral or bilateral numbness in the medial (ulnar) portion o the hand(s) suggests ulnar neuropathy due to compression o the ulnar nerve at the medial elbow, which can occur in patients who are bedbound or prolonged periods. I severe, weakness o intrinsic hand muscles may be present. By a similar mechanism in bedbound patients, the peroneal nerve may be compressed at the bular head, especially 695

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Figure 98 2 Patterns of sensory disturbances. A. Brain hemisphere lesions cause contralateral sensory disturbances in the face and body. B. Brainstem lesions cause ipsilateral sensory disturbances in the face and contralateral sensory disturbances in the body. C. Transection of the spinal cord causes sensory disturbances bilaterally below the level of the lesion. D. Central cord lesions at the cervical level cause disturbances in pain and temperature sensation in a cape-like distribution. E. Alesion of one side of the spinal cord causes ipsilateral loss of vibration sense and proprioception and ipsilateral weakness below the level of the lesion and contralateral loss of pain and temperature sensation below the level of the lesion. F. Aroot lesion causes sensory disturbances in the region supplied by the affected root. G. Anerve lesion causes sensory disturbances in the region supplied by the affected nerve. H. Polyneuropathy causes sensory disturbances that begin in the distal extremities. 696

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Lesions o the spinal cord cause de cits below the level o the lesion. The type (sensory, motor, or both) and extent o these de cits (arms, legs, unilateral, bilateral) depend on the location and size o the lesion. The spinal cord can be a ected by trauma, vascular pathology (eg, epidural hematoma, dural arteriovenous stula, in arction), in ection (eg, viral myelitis, epidural abscess, tuberculosis, syphilis [tabes dorsalis], HIV-associated vacuolar myelopathy, HTLV-1, schistosomiasis, cysticercosis), in ammatory conditions (eg, multiple sclerosis, neuromyelitis optica, transverse myelitis, Sjögren’s syndrome, systemic lupus erythematosis), neoplasm (eg, primary and metastatic tumors to the spinal column, cord, or dura mater), metabolic conditions (eg, vitamin B12 and copper de ciency), and degenerative conditions (eg, Friedreich’s ataxia). An initial di erential diagnosis can be generated rom the time course o symptom onset, associated symptoms presented in the history, and eatures o the physical examination, but MRI is o ten required to distinguish between underlying etiologies. It should be noted that an MRI o the entire spine can be use ul to evaluate or spinal cord compression in the appropriate context, but o ten does not have the resolution o MRI o individual spinal levels (eg, MRI o the cervical spine). It is there ore ideal to attempt to localize the level o the lesion as precisely as possible on the physical examination. I the upper extremities are involved, the lesion must involve the cervical spine. It is important to note that the spinal cord ends at approximately L1, with only the roots o the cauda equina in erior to this level. There ore, upper motor neuron ndings on examination (brisk re exes, Babinski sign, clonus, etc) in a patient with isolated bilateral lower-extremity symptoms suggest localization to the thoracic or cervical cord rather than the lumbar region. A use ul clinical sign o spinal cord pathology is the nding o a spinal level—a level on the back at which there appears to be a change in sensation with diminished sensation below the level and preserved sensation above it. This is not only quite speci c or spinal cord pathology but can aid in localization so as to determine the level at which neuroimaging analysis should be ocused. The ollowing are the main clinical patterns associated with di erent types o spinal cord lesions and their most common underlying etiologies. Complete transection. A ull-thickness lesion o the spinal cord will produce complete paralysis and sensory loss in all modalities below the level o the lesion. I the lesion is acute (eg, trauma, early transverse myelitis), the upper motor neuron signs that would be expected with a spinal cord lesion may not yet be present, leading to diagnostic uncertainty with respect to the possibility o

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With the exception o trauma, it is rare or the entire plexus to be a ected by the disease processes mentioned. When numbness occurs in an entire limb or an entire unctional component o a limb that spans multiple nerves/roots (eg, the entire hand or the entire leg), a central nervous system etiology should be considered. Ganglionopathy re ers to disease processes a ecting the dorsal root ganglia. Ganglionopathy causes sensory abnormalities including paresthesias and impaired proprioception. The proprioceptive de cit causes incoordination and gait unsteadiness due to sensory ataxia (ie, ataxia due to absence o proprioceptive input rather than due to cerebellar dys unction). Re exes are typically absent. Strength is generally spared since motor pathways are not involved. This is an important clinical syndrome to recognize as its di erential diagnosis is somewhat circumscribed: autoimmune disease (most commonly Sjögren syndrome), in ection (most commonly HIV), vitamin B6 toxicity, paraneoplastic syndrome (most commonly anti-Hu due to small cell lung cancer), and chemotherapy-induced (most commonly platin-based chemotherapies).

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i the legs are requently crossed. The presence o oot drop in peroneal neuropathy is usually more salient than the sensory disturbance that a ects the lateral cal and dorsum o the oot. Weakness o hip exion and knee extension caused by emoral neuropathy requires evaluation or retroperitoneal hematoma in patients who are anticoagulated or who have undergone emoral artery catheterization; sensory disturbances (o the anterior thigh and medial leg) are typically less prominent than weakness. Polyneuropathy. The clinical presentation and di erential diagnosis o symmetric polyneuropathy is discussed in detail in Chapter 213. Most polyneuropathies are chronic, and although they may be present in hospitalized patients, are unlikely to be a cause or hospital admission. Acute polyneuropathy is seen in Guillain-Barré syndrome. Although the classic presentation is one o ascending paralysis (legs be ore arms), the initial symptoms may be sensory in nature (classically paresthesias in the eet), and sensory-only variants do occur. Further details regarding the diagnosis and treatment o GuillanBarré are discussed in Chapter 213 (Peripheral Neuropathy). The main di erential diagnosis in a case o rapidly ascending weakness and/or sensory changes is Guillain-Barré syndrome versus a spinal cord lesion (eg, transverse myelitis or epidural abscess). Notably, upper motor neuron signs (hyperre exia, clonus) may be absent in the acute phase o a myelopathy. The presence o early bowel and/ or bladder dys unction, back pain, and/or a spinal level are suggestive o spinal cord pathology. Other causes o acute polyneuropathy to be considered include heavy metal toxicity, porphyria, and HIV in ection, particularly at the time o seroconversion. Critical illness polyneuropathy is discussed in Chapter 213 (Peripheral Neuropathy). Weakness is generally the presenting eature rather than associated sensory loss. Sensory loss aids in the distinction between critical illness polyneuropathy and critical illness myopathy since the latter should have no associated sensory abnormalities, though the two commonly occur together. Mononeuropathy multiplex re ers to the sequential involvement o individual nerves. For example, a patient may develop a wrist drop (radial neuropathy) ollowed by a oot drop (peroneal neuropathy). This can be seen in systemic vasculitis due to nerve in arction, which is typically pain ul. Mononeuropathy multiplex can also be seen in leprosy, hepatitis C or HIV in ection, and systemic autoimmune diseases (eg, sarcoidosis). Radiculopathy typically causes radiating pain rom the neck or back into the distribution o an individual nerve root, and may be accompanied by paresthesias, sensory loss, and/or weakness in the a ected root distribution. Compression due to degenerative disc disease is a common etiology o radiculopathy. Polyradiculopathy can also be caused by local compression or invasion by malignancy or in ectious radiculitis (eg, Lyme, HSV, CMV; CMVradiculitis is generally only seen when CD4 < 50). When polyradiculopathy is a cause o sensory or motor abnormalities, these tend to be pain ul and asymmetric, compared to polyneuropathy, which is more commonly symmetric. Plexopathy. When unilateral sensorimotor symptoms do not t into the distribution o a single nerve or root, the possibility o a lesion o the brachial or lumbosacral plexus should be considered. Motor eatures usually predominate over sensory disturbances in plexopathies, though the latter are commonly present. The brachial and lumbosacral plexuses can be a ected by trauma (injuries that stretch the axilla or depress the shoulder or the brachial plexus; pelvic injuries or the lumbosacral plexus), malignancy (lung and breast or the brachial plexus; colorectal, gynecologic, urologic or the lumbosacral plexus), surgery (sternotomy or the brachial plexus; pelvic surgery or the lumbosacral plexus), radiation, and in ammatory conditions (eg, Parsonage-Turner syndrome or the brachial plexus; diabetic amyotrophy [also known as diabetic lumbosacral radiculoplexus neuropathy] or the lumbosacral plexus).

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Guillain-Barré syndrome. Bowel and/or bladder dys unction and a spinal level are suggestive o a spinal cord etiology o accid paralysis and/or sensory loss in the acute setting. Hemicord/Brown-Séquard Syndrome a ects one hal o the spinal cord. In addition to ipsilateral paralysis below the level o the lesion, this syndrome is characterized by dissociated sensory loss: ipsilateral loss o proprioception and vibration and contralateral pain and temperature loss below the lesion (see above). This pattern o symptoms is generally caused by penetrating trauma, although a unilateral tumor or an eccentric demyelinating lesion may produce this syndrome. Central cord syndrome. A syrinx is an enlargement o the central canal o the spinal cord, occurring most commonly at the cervical level. A syrinx can be caused by a spinal cord tumor, spine trauma, or can be associated with Chiari mal ormation type I. Enlargement o the central canal rst a ects the crossing anterolateral (spinothalamic) bers leading to loss o pain and temperature in the upper extremities with sparing o vibration and proprioception. Due to the lamination o these pathways, the upper extremities are a ected rst, leading to the so-called “cape-like” distribution o sensory ndings. Subacute combined degeneration re ers to combined degeneration o the corticospinal tracts and the dorsal columns. This is most commonly due to vitamin B12 de ciency, but can also be caused by copper de ciency. The combined pathology o the corticospinal tracts and dorsal columns leads to weakness with impaired proprioception and vibration sense. Impaired proprioception can lead to sensory ataxia, unsteady gait, and Romberg sign. Vibration sense is typically diminished distally. Since vitamin B12 de ciency and copper de ciency can also cause neuropathy, there may be both peripheral (lower motor neuron) and central (upper motor neuron) eatures on examination (eg, hypore exia with upgoing toes, or brisk knee re exes with absent ankle re exes), classi ed as myeloneuropathy. In addition to pernicious anemia and malabsorption, vegetarianism and gastric bypass can predispose to vitamin B12 de ciency. Excess zinc consumption ( rom denture cream or supplementation) and gastric bypass are common causes o copper de ciency. Anterior cord syndrome. The anterior spinal cord is particularly vulnerable to ischemia due to lack o extensive collateralization. The anterior spinal artery territory comprises the anterior two thirds o the spinal cord, including the anterolateral and corticospinal tracts, but not the dorsal columns. Patients with anterior spinal artery in arction there ore present with bilateral paralysis and diminished or absent pain and temperature sensation below the level o the lesion, but preserved proprioception and vibration sensation. This is most commonly seen with abdominal aortic aneurysm (AAA) rupture or a ter surgical repair o AAA. Tabes dorsalis. Tertiary neurosyphilis can a ect the brain (causing dementia) and/or the spinal cord (causing tabes dorsalis). The posterior columns and dorsal roots are primarily a ected in tabes dorsalis, and there ore the clinical eatures are predominantly due to impaired proprioception: gait unsteadiness, sensory ataxia, absent or diminished vibration sense and proprioception, and Romberg sign. Parestheisas, lancinating pain, bladder dys unction, and Argyll Robertson pupils are common accompanying eatures. Saddle anesthesia due to lesions of the cauda equina and/or conus medullaris. Sensory changes in the perineal region (saddle anesthesia), o ten accompanied by bowel and/or bladder dys unction, should alert the clinician to the possibility o pathology a ecting the conus medullaris (the most in erior portion o the spinal cord) or the cauda equina (the lumbar and sacral nerve roots). Classically, cauda equina syndrome is more likely to cause pain and asymmetric symptoms and signs compared to conus medullaris syndrome. However, the two can be dif cult to distinguish clinically and both require MRI o the lumbosacral spine to evaluate or the underlying 698

etiology. Potential pathology in this region includes compression by tumor or prolapsed disc, in ection (eg, epidural abscess or viral polyradiculitis), and in ammatory diseases such ankylosing spondylitis and sarcoidosis. Brainstem As mentioned previously, the sensory pathways in the brainstem are rarely a ected in isolation. When they are a ected as part o the lateral medullary syndrome due to in arction in the territory o the posterior in erior cerebellar artery, the sensory loss is o ten ‘crossed,’ with acial sensory loss contralateral to sensory loss in the extremities and torso. Trigeminal nerve Isolated acial numbness can occur with lesions o the trigeminal nerve or with small lesions o the brain or brainstem. Patients also sometimes use the term numbness to describe the sensation o acial weakness that occurs in Bell’s palsy, although true sensory de cits are not common in this condition. Facial numbness due to pathology o the trigeminal nerve can be caused by skull base lesions (eg, tumor, leptomeningeal metastases), in ammatory disease (eg, Sjögren’s syndrome, sarcoidosis), perineural spread o head and neck cancers (particularly squamous cell cancer o the skin), and dental pathology. Numbness in the chin (numb chin sign) raises the specter o metastatic malignancy a ecting the distal trigeminal branches in the mandible or the mandibular portion o the trigeminal nerve in the skull base, and may be the presenting eature o systemic malignancy. Brain A patient presenting with acute-onset numbness limited to one side o the body should be evaluated or stroke. Lacunar in arction o the thalamus can produce contralateral sensory loss in isolation. When cerebral in arction is the etiology o alteration in sensation, the patient generally describes sensory loss in the acute period rather than paresthesia or pain, although the latter may emerge later. Patients with isolated somatosensory cortex in arction may describe the a ected limb to be unctioning abnormally despite lack o clear de cits on routine motor and sensory examination. However, subtle signs such as agraphesthesia (inability distinguish numbers traced on the palm) or neglect to double simultaneous stimulation (inability to detect bilateral simultaneous sensory stimulation) may be clues to a cortical lesion. In addition to vascular etiologies, the di erential diagnosis or acute-onset unilateral neurologic de cits includes migraine and seizure. Sensory disturbances may accompany migraine and may precede the emergence o the headache, and sometimes occur in the absence o the headache in patients with a history o migraine (ie, migraine aura without headache, a.k.a. acephalgic migraine). In contrast to the loss o sensation commonly associated with acute stroke, migraine-associated sensory disturbances are typically positive phenomena such as paresthesias that tend to spread over minutes. Positive somatosensory phenomena may also be caused by seizures with origin in or spread to the somatosensory cortex, with paresthesias typically spreading over seconds. The development o localized sensory loss over hours to days due to a lesion in the brain can suggest an in ammatory process (eg, a demyelinating lesion) or an in ectious process (eg, cerebral abscess). A more indolent development o ocal sensory disturbance o cerebral origin could be suggestive o neoplasm. Nonneurologic causes of sensory disturbances Electrolyte abnormalities (eg, hypocalcemia) and hyperventilation can cause paresthesias, classically periorally and in the distal

Unilateral

Fa ce only: He mibody Trig e mina l ne rve a nd fa ce Bra ins te m S ma ll he mis p he ric le s ion

Fa ce a nd ips ila te ra l body Ce re b ra l he mis p he re

Monone uropa thy

C H A P T E R 9 8 N u m b n e s s : A L o c a l i z a t i o n B a s e d A p p r o

Bilateral

He mibody without One limb fa ce Lowe r b ra ins te m S p ina l c ord (s ma ll c e re b ra l le s ion a ls o p os s ib le )

Fa ce a nd contra la te ra l body: Bra ins te m or multip le le s ions

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With the above patterns and their di erential diagnoses in mind, the examiner seeks to elicit rom the history the nature o the sensory complaint (ie, absence o sensation, paresthesia, or both), the location(s) o the symptoms (acknowledging that this can be challenging or patients to localize precisely), the timing o symptom onset (acute, subacute, chronic), associated symptoms (pain, weakness, incoordination), and any prior neurologic events or de cits. The physical examination seeks to determine the distribution o the sensory abnormality, the modalities that are altered (ie, pain, temperature, vibration, and/or proprioception), and any associated eatures that provide clues to peripheral versus central nervous system etiology (eg, altered deep tendon re exes, presence o pathologic re exes such as a Babinski sign). The sensory examination is considered by many practitioners to be the most subjective aspect o the neurologic examination, and can be challenging to interpret. One approach is to proceed rom general comparisons to more speci c ones. For example, one can begin by comparing pinprick sensation between the same points in the le t and right hands in general or di erences between the sides be ore seeking to circumscribe the extent o the de cit in the a ected hand, or comparing the most distal point (the big toe) to a more proximal one (the thigh) be ore assessing or the precise location at which sensation changes when proceeding rom distal to proximal. Assessing or a spinal level (see above) is particularly use ul when there are acute-onset de cits in sensation in the bilateral extremities such that the upper motor neuron eatures o myelopathy (i present) may have not yet emerged. With more subacute or chronic presentations o bilateral sensory disturbances, hyperreelxia, clonus, Babinski sign, and/or spasticity, i present, allow or localization in the spinal cord i the motor pathways are involved. Hypore exia or are exia in this context suggest peripheral nervous system pathology. A Romberg sign or sensory ataxia suggest a de cit in proprioception, which can localize to the peripheral nerves, dorsal root ganglia,

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APPROACH TO THE PATIENT WITH NUMBNESS

or dorsal columns. Sensory ataxia due to impaired proprioception can be distinguished rom cerebellar ataxia by several eatures on the nger-nose test. Sensory ataxia tends to lack the rapid oscillations perpendicular to the plane o movement seen in cerebellar ataxia, appearing as more o a searching movement that may circle toward the examiner’s nger and the patient’s nose. In sensory ataxia, nger-nose testing becomes highly inaccurate when the patient closes the eyes, whereas a patient with normal proprioception can maintain reasonable accuracy with the eyes closed. The localization in conjunction with the time course yields an initial di erential diagnosis. Sudden-onset sensory de cits localizable to the brain may be vascular, migrainous, or epileptic, but can also be due to acute electrolyte disturbances. Acute-onset sensory disturbances due to stroke, migraine, or seizure are typically unilateral, whereas systemic etiologies typically cause bilateral sensory symptoms. Sudden-onset symptoms localizing to the spine may be due to spinal cord in arction or spinal cord compression due to acute disc prolapse or spine racture. Acute onset mononeuropathy suggests nerve in arction, especially when pain ul, as can be seen in vasculitis. Sensory disturbances o subacute onset can be seen in in ectious or in ammatory/demyelinating conditions o the peripheral or central nervous system, but can also occur with metabolic abnormalities (eg, vitamin B12 de ciency). More chronic development o sensory alterations can occur with systemic disease (eg, peripheral neuropathy due to diabetes, cervical spinal cord compression due to rheumatoid arthritis); primary or metastatic malignancy o the brain, spine, or compressing the brachial or lumbar plexus; or degenerative conditions. CT scan (o the brain or spine) is generally per ormed in the acute setting to evaluate patients with sudden-onset neurologic de cits, but MRI has higher resolution and sensitivity or the detection o nearly all types o pathology o the brain and spinal cord with the possible exception o acute hemorrhage. Contrast administration can aid in the detection and characterization o tumors, acute in ectious or in ammatory lesions, and meningeal processes (in ectious, in ammatory, or neoplastic). When the di erential diagnosis includes neuropathy, radiculopathy, and/or plexopathy, electromyography (EMG)/nerve conduction studies can aid in localization, and can also provide an objective measurement o the extent o injury to a given nerve, which can be use ul in prognosis or recovery.

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extremities. Sensory disturbances can also accompany panic attacks.

S pina l cord

Loca lize d re gion of limb

Ra diculopa thy

Pe riphe ra l ne uropa thy

S ys te mic e tiology (e g, e le c trolyte a b norma lity, a nxie ty)

Entire limb

P lexopa thy

Ce ntra l le s ion

Figure 98 3 Most common lesion localization for numbness by region of body. 699

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SUGGESTED READINGS

Herskovitz S, Scelsa S, Schaumburg H. Peripheral Neuropathies in Clinical Practice. New York, NY: Ox ord; 2010.

Biller J, Brazis PW, Masdeu JC. Localization in Clinical Neurology. 6th ed. Philadelphia, PA: Lippincott Williams and Wilkins; 2011.

Mauermann ML, Burns TM, eds. Peripheral nervous system disorders. Continuum. 2014;20(5):1161-1525.

Daro RB, Fenichel GM, Jankovic J. Bradley’s Neurology in Clinical Practice. 6th ed. Philadelphia: Elsevier; 2012.

Ropper AH, Samuels MA, Klein JP. Adams and Victor’s Principles of Neurology. 10th ed. New York, NY: McGraw-Hill; 2014.

Evans RW, Kirby S, Purdy RA. Numb Chin Syndrome. Headache. 2008;48:1520-1524.

Sheikh SI, Amato AA. The dorsal root ganglion under attack: the acquired sensory ganglionopathies. Pract Neurol. 2010;10:326-334.

99

CHAP TER

Pain Samer Abdel-Aziz, MD Meredith C.B. Adams, MD, MS

Key Clinical Questions

CASE 99-1 A 76-year-old emale with a history o dementia, hypertension, hypercholesterolemia, coronary artery disease, chronic obstructive pulmonary disease, and chronic low back pain su ered a right tibia racture. The orthopedic surgery service surgically repaired her leg and trans erred her to the primary service or management o multiple co-morbidities. On the second postoperative day, severe pain has limited her movement and ability to work with physical therapy or use the bathroom acilities. Home medications include atorvastatin, metoprolol, ramipril, hydrochlorothiazide, ipratropium, albuterol metered dose inhaler, and oxycodone controlled-release 20 mg twice a day. Her vital signs were: heart rate is 120 beats per minute, blood pressure 150/95 mm Hg, SpO2 95% on 2 L o oxygen, and temperature 37.2°C. Laboratory results were notable or a glucose level o 212 mg/dL. Her postoperative pain is managed by 2 mg o intravenous (IV) morphine every 3 hours. On this regimen she does continue to report severe right leg pain.

INTRODUCTION

■ DEFINITION AND CLASSIFICATION 1

What are the goals o pain therapy?

2

How is the sensation o pain measured?

3

What are the types o pain?

4

How do patient comorbidities a ect pain management?

5

What are the most appropriate and e ective pain treatment options available?

Pain is the leading cause o both adult outpatient and emergency department visits, impacting both inpatient and outpatient care or over 100 million Americans annually. The International Association or the Study o Pain de nes pain as an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms o such damage. Pain may be classi ed in multiple domains. Currently the majority o pain classi cations rely on various parameters o pain experience such as anatomy, duration, etiology, body system, severity, unctioning and mechanism. The rst is the classi cation based on the underlying etiology o the pain. Nociceptive pain re ers to the direct tissue injury rom a noxious stimulus. In ammatory pain re ers to the release o in ammatory mediators that perpetuate and modulate nociceptive input. Direct injury to nerves results in a third type o pain, neuropathic pain, whereby the nature o sensory transmission is altered and accompanied by pain requently described as a burning type o pain. Although these are described as discrete types o pain, they more o ten represent a continuum o the same injury. Surgical incision is a model o nociceptive injury that produces an in ammatory response. Incising the primary nociceptors in the skin with subsequent development o in ammatory neuritis can result in neuropathic pain. The second domain o classi cation re ers to the anatomic location o pain. In this category, pain can be described as either somatic or visceral. Somatic pain re ers to a well-localized sensation related to skin, muscle, and bone, whereby visceral pain is poorly localized and is usually in response to distention o the internal organs such as the colon or small bowel, or compression or in ammatory injury, which occurs in pancreatic cancer or pancreatitis. The third domain classi es pain based on the temporal nature o the pain. Acute pain usually re ers to a neurophysiologic response to a noxious stimulus, a response expected to resolve with completion o wound healing. In contrast, chronic pain persists beyond the expected time course o an acute injury and its repair process. Chronic or persistent pain does not simply suggest that a given time 701

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interval has passed. Rather, such a diagnosis implies development o multiple neurophysiologic changes that alter the undamental balance between noxious stimuli and their inhibitory mechanisms. Such changes occur rom the peripheral nerve to the dorsal horn o the spinal column, interneurons throughout the spinal cord, to the thalamus and cortical circuits. These changes ultimately result in remodeling in the organization o the central nervous system.

PRACTICE POINT

•

Poorly controlled pain may present through multiple parameters including vital signs and laboratory values, rein orcing the impact o a patient under signi cant physiologic and psychological stress. Mani estations o this stress can include myocardial ischemia, immunosuppression, impaired wound healing, and thromboembolic events.

PRACTICE POINT Although the clinician must be aware that the patient may manipulate the pain report, it is imperative to rst validate the patient’s understanding o his or her pain by receiving his or her report with an unbiased view.

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Pain is a subjective phenomenon and results rom a patient’s understanding o the physical and a ective impact the sensation has had on them. There are multiple quantitative pain evaluation scales. Although these are subjective reports with no way to veri y the answer’s “truth,”these scales have been used or decades and correlate well to experimental and clinical pain responsiveness. Numerous actors can in uence perception o pain including cultural components, particularly when you de ne culture to include categorization such as Veterans, athletes, and other nonethnic cultures. The patient’s pain history has speci c components to direct diagnostic and therapeutic options. Key pain speci c in ormation or the inpatient setting may involve the provocative and palliative components o pain. Many patients experience their pain primarily with activity, such as physical therapy. This may impact the design o therapeutic regimen to avoid oversedation at rest and suf cient pain control to acilitate participation in therapy. Another important aspect when assessing the inpatient with pain is to consider their baseline home pain scores. Patients may have baseline pain scores greater than 4 at home due to other co-morbid pain conditions. Normalization o pain scores to baseline home level that allows unction may be a pragmatic goal in patients with higher scores at baseline. The numerical rating scale (NRS) is the most commonly used tool or the evaluation o pain severity. Patients are asked to rate their pain on a scale o 0 to 10, with 0 translated as “no pain” and 10 the “worst pain imaginable.”The visual analog scale (VAS) allows patients to mark a point on a 10-cm line that corresponds to the level o their pain. Using the 4-point verbal rating scale (VRS), patients categorize their pain as none, mild, moderate, or severe. The NRS and VAS demonstrate excellent agreement, and o er superior discriminating ability to the categorical VRS. All o these scales are subjective and can be use ul only when comparing pain severity within the same patient at di erent times or during di erent activities, but are not use ul in comparing pain severity in di erent patients since di erent patients have di erent perception o pain and its severity. Although the practitioner must be aware that the patient can manipulate the pain report, it is imperative to rst receive the patient report with an unbiased opinion. Patients with pain may have comorbidities that pose a challenge when it comes to pain evaluation. The above case study discusses a patient with dementia. Standard pain reporting scales are ine ective in demented patients, unconscious patients, or patients unable to communicate. Pain scales such as MOBID-2, Checklist o Nonverbal Pain Indicators, and Doloplus-2 have been designed or patients with dementia or in an assisted living acility. These scales have strong conceptual and psychometric support; however they are an indirect measure o the patient’s pain and may be in uenced by the intrinsic bias o the health care provider. 702

Timing and activity are relevant to the interpretation o pain scores. Reported pain scores may re er to the past hour, 24 hours, week, or month. Average, maximum, and minimum pain scores help ascertain the patient’s range o pain. Twenty-hour pain scores may give the best in ormation regarding overall trends o pain status. Pain scores may also be described as rest or static versus active or dynamic to correlate the given score with activity level. Pain scores reported by the patient when resting may not re ect pain-based limitations on activity. Because the goal o pain treatment usually includes improvement in mobility or unction to decrease thromboembolic and pulmonary complications, addressing only rest/static pain may result in a ailure to maximize the bene t o pain control. The above scales are applied to all types o pain: acute, chronic/ persistent, and cancer pain. The added complexity o chronic/ persistent or cancer pain can require more multi aceted evaluation tools. Additional pain scales can be administered to these patients to better deliver more targeted pain care, but they will not be discussed as they are beyond the scope o this chapter. The history should be supplemented by a ocused pain exam, incorporating knowledge o muscle innervation and dermatomes (Table 99-1) to de ne the patient’s pain pattern and guide treatment approaches.

■ TREATMENT OF PAIN Treatment o pain may utilize our primary modalities: medications, interventions, behavioral therapies and physical therapy/ complementary treatments. This review will ocus on the medical and interventional management o pain, although behavior and complementary treatments are essential components o improving the overall pain state in patients with persistent pain.

■ SYSTEMIC ANALGESIA Opioids Opioid analgesics remain the most common treatment or both acute and chronic pain. By activating the mu opioid receptor throughout the CNS, opioids modulate the perception and TABLE 99-1 Sensorimotor Nerve Distribution Movement Shoulder abduction Elbow lexion Elbow extension Finger lexion Finger abduction Hip lexion Knee Extension Ankle dorsi lexion (heel walk) Knee lexion

Nerve Root C5 C5-C6 C6-C7 C8 T1 L2-L3 L3-L4 L4-L5

Key Sensory Area C5: lateral upper arm C6: thumb C7: middle inger C8: i th inger T1: ulnar orearm L2: medial midthigh L3: medial knee L4: medial cal

L5-S1

Ankle planter lexion (toe walk)

S1-S2

L5: lateral cal and dorsum oot S1: posteriolateral oot and ankle

H A P T E R

0.05 0.07

9

H/R H/R

9

Every 4-6 h/as needed Every 4-6 h/as needed

P

15-60 mg 50-100 mg

a

Dose Interval Every 4-6 h/as needed 2-3 times a day Every 4-6 h/as needed 2-3 times a day Every 3-4 h/as needed Every 3-4 h/as needed Every 3-4 h/as needed Every 72 h 3 times a day Every 4-6 h/as needed

Conversion actor to PME 1 0.33 0.5 0.5 6.7 1.3 100 25 1 0.3

i

Dose 2-5 mg 15-30 mg 5-10 mg 15-20 mg 0.5- 2 mg 2-4 mg 25-100 mcg 12 mcg/h 2.5-5 mg 5/325 mg

Metabolism and Excretion H/R H/R H/R H/R R/H R/H H/R H/R H/R H

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Opioid Morphine (IV) Morphine (PO) Oxycodone- IR (PO) Oxycodone-SR (PO) Hydromorphone (IV) Hydromorphone (PO) Fentanyl (IV) Fentanyl transdermal Methadone (PO) Hydrocodone/ Acetaminophen (PO) Codeine (PO) Tramadol (PO)

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TABLE 99-2 Common Opioid Analgesics

H, hepatic; IR, immediate release; PME, parenteral morphine equivalent; R, renal; SR, sustained release.

transmission o pain ul stimuli. Opioid-based therapies are not limited by a ceiling e ect; increasing doses will theoretically yield increasing analgesic e ects even at extremely high doses. However, increasing doses o opioids are unctionally limited by side e ects such as nausea, vomiting, constipation, sedation, and respiratory depression. When used or acute pain, the most common routes o systemic opioid administration include intravenous (IV), intramuscular (IM), and per os (by mouth) (PO). Parenteral routes may also include transdermal (TD), subcutaneous (SC), transmucosal (TM), or iontophoretic transdermal (ITD). Epidural and intrathecal administration is also used in a variety o settings. Intravenous administration o opioids ensures a rapid, predictable onset and distribution o analgesic unctioning, making this the avored route or the initial treatment o severe acute pain. Intramuscular and enteral routes may result in delayed onset o e ects, limiting their e ectiveness in the acute pain setting. Similarly, TD (ITD excepted) and SC routes o administration have considerably delayed onset and are more o ten appropriate or long-term use such as in chronic pain or palliative care settings. Table 99-2 lists several opioids commonly prescribed or acute and chronic pain medicine. Commonly, patients will experience excellent pain relie ollowing administration o opioids. However, there may be a variable response to di erent ormulations and pharmacologic compounds resulting rom genetic polymorphisms involving mu-opioid receptor activation, receptor distribution, opioid metabolism, and the type o pain. Opioids are o ten best at treating static, nociceptive pain such as postsurgical pain; however they are less e ective or dynamic or movement-related pain or neuropathic pain. Further, opioids are o ten ine ective in the treatment o bone racture pain such as the pain experienced by the patient in the case study. Opioid conversion: In the course o transitioning rom severe acute

pain to moderate, subacute pain, physicians will requently transition the patient rom parenteral to oral opioid administration. 1. Calculate the patient’s 24-hour opioid use. 2. Convert this to “parenteral morphine equivalent” (PME). 3. The total oral dose prescribed to the patient is commonly less than 100% o the parenteral dose equivalent; this decision is guided by the clinical milieu o the patient including “the patient’s recovery rom his or her pain.”

4. Consider the division o this requirement into short and/or long-acting opioids. This decision depends greatly upon the patient, the timing o his or her pain, and the nature o his or her pain. 5. Fi ty percent o the 24-hour PME may be given as a sustained preparation, and 50% as shorter-acting, immediate-release medications ordered as needed. 6. Numerous conversion tables and calculators are available to assist the physician with opioid conversion. See www.hopweb.org. Nonsteroidal anti inflammatory agents NSAIDs NSAIDs exert their analgesic e ect via inhibition o the cyclooxygenase (COX) enzyme, thus inter ering with prostaglandin (PG) production. Prostaglandins modi y nociceptive thresholds at both peripheral and central sites. By limiting production o PG rom COX-1 and COX-2, NSAIDs o er e ective analgesia or mild to moderate pain. Further, this mechanism o action apart rom the mu-opioid receptor provides a strong supplement to opioids during treatment o moderate to severe pain. Although opioid sparing, NSAIDs do have a ceiling e ect, beyond which increasing doses will yield no increase in analgesia. Clinically, NSAIDs decrease pain associated with orthopedic injuries, and those with extensive prostaglandin involvement such as pain rom uterine contraction and muscle in ammation. However, the risk o bleeding and mixed evidence regarding inter erence with union o ractures and spinal surgery necessitates involvement o the operative team in the decision to add NSAIDs. Traditionally, NSAIDs were nonspeci c or the iso orms o cyclooxygenase, COX-1 and COX-2. COX-1 is constitutively expressed in nearly all human tissues, while COX-2 is ocally expressed with in ammation. Blockade o COX-1 may promote development o gastrointestinal irritation and bleeding. NSAIDs as a class may also inter ere with autoregulation o renal per usion. To minimize the e ects o gastrointestinal irritation and bleeding, drug development turned to selective COX-2 inhibitors. Although e ective in minimizing gastrointestinal bleeding, selective COX-2 inhibitors may result in a prothrombotic milieu that may increase the risk o myocardial in arction. Acetaminophen, a para-aminophenol derivative (not an NSAID), may represent a special class o NSAIDs. While its mechanism o action is not completely understood, there is evidence o antagonistic activity against COX-2, and a splice variant o COX-1 named COX-3. Notably, acetaminophen appears to not inhibit peripheral 703

Drug Gabapentin

Start Dose 300 mg/d

Maximum Dose 3600 mg/d

Pregabalin

25 mg/d

600 mg/d

Tricyclic antidepressants Venla axine Duloxetine Milnacipran Carbamazepine (oxcarbazepine)

25 mg/d (NB: plasma level) 37.5 mg/d 60 mg/d 12 mg/d 300 mg/d (NB: plasma level)

75-150 mg/d (NB: plasma level) 25-375 mg/d

Tramadol

50 mg/d

Lamotrigine

25 mg/d * (NB: plasma level) 5–10 mg/d, titrate substitute with longacting opioids

100 mg/d 1200-1800 mg (1/3 higher dose or oxcarbazepine) (NB: plasma level) 400 mg/d

Documented E ect PHN, PDN, mixed neuropathic pain PHN, PDN, mixed neuropathic pain, central pain PHN, PDN, central pain, mixed neuropathic pain Pain ul neuropathy Pain ul neuropathy Pain ul neuropathy Trigeminal neuralgia

Pain ul neuropathies

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TABLE 99-3 Neuropathic Pain Medication Guidelines

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Trigeminal neuralgia, poststroke central pain PHN, PDN, postamputation pain PHN, traumatic nerve injury PHN, PDN, HIV

Side E ects Sedation, dizziness, edema Sedation, dizziness edema Cardiac, anticholinergic, sedation Sedation Sedation Sedation Sedation, dizziness, ataxia

Sedation, dizziness, obstipation Sedation, tremor, rash Sedation, dizziness, tolerance, drug abuse Allergic reaction

PDN, peripheral diabetic neuropathy; PHN, postherpetic neuralgia.

To be titrated slowly.

*

Reproduced, with permission, rom Jensen TS, et al. Pharmacology and treatment o neuropathic pains. Curr Opin Neurol. 2009;22:467-474.

COX-1, which may explain its avorable sa ety pro le in regards to gastrointestinal, hematological, cardiovascular, and renal e ects seen with other NSAIDs and selective COX-2 inhibitors. In assessing comparative ef cacy, the number o patients needed to treat (NNT) or at least a 50% reduction in pain a ter 4 to 6 hours or 1 g o acetaminophen is 4.4, which compares avorably to 650 mg o aspirin or 100 mg o ibupro en. A more typical dose o ibupro en, 400 mg, however, had an NNT o only 2.3. Celecoxib, a selective COX-2 inhibitor, has a NNT o 4.5 at 200 mg when compared with placebo or postoperative pain. Anticonvulsants and antidepressants Adjuvant medications can add value to a multimodal treatment plan (Table 99-3) depending on the pain indications. Selected anticonvulsants, like gabapentin and pregabalin are considered the rst line therapy in the treatment o neuropathic pain. Gabapentin and pregabalin work by binding to voltage gated calcium channels on primary a erent neurons, reducing the release o neurotransmitters rom their central terminals. The e ective dose o gabapentin is 1800 to 3600 mg daily usually divided in three doses, while or pregabalin, the e ective dose is 300 to 600 mg daily usually divided in two doses. Start at low doses and titrated up to the e ective dose over several weeks to avoid or decrease the main side e ects o these medications (somnolence and dizziness). The gabapentinoids have a clear role in the treatment o postoperative pain when given in the perioperative period (pre- and postoperatively) in a number o major orthopedic and gastrointestinal surgeries. In the acute and chronic pain setting, they have been shown to be opioid sparing and show promise as success ul adjuvant analgesics. Antidepressant medications, mainly tricyclic antidepressants (TCAs) and selective serotonin and norepinephrine reuptake 704

inhibitors (SSNRIs) are commonly used in the treatment o neuropathic pain. TCAs, speci cally amitriptyline and nortriptyline, are e ective in treating neuropathic pain. The starting dose or TCAs is 25 mg at bedtime slowly titrated to decrease the side e ect pro le while achieving pain relie up to a maximum dose is 100 to 150 mg daily. Evening dosing takes advantage o one side e ect, somnolence, and may acilitate sleep and decrease pain. The most common side e ect o TCAs is dry mouth. TCAs are not recommended in patients with ischemic heart disease or in patients with dementia due to anticholinergic e ects. Selective serotonin and norepinephrine reuptake inhibitors (SSNRIs) like duloxetine and milnacipran e ectively treat neuropathic pain. Their analgesic e ect is separate rom their antidepressant e ects, and bene t chronic pain patients who have concomitant depression. Duloxetine is e ective at a dose o 60 mg once daily, while milnacipran is used at 100 mg daily divided in two doses. The most common side e ects o these medications are nausea, somnolence and dizziness, they as well need to be started at low doses and titrated up to the e ective dose. Combining an anticonvulsant like gabapentin or pregabalin with an antidepressant like duloxetine or amitriptyline may be very e ective in treating neuropathic pain allowing lower dosing and ewer side e ects.

CASE 99-1 (continued) In managing the postoperative patient with dementia the goal is to minimize her opioid requirement (and side e ect burden) by using NSAIDs and gabapentinoids as adjuncts. The patient has no history o renal insuf ciency or gastric ulceration, and scheduled

H A P T E

Continuous Basal In usion Rate * 1-2 mg/h 0.2-0.4 mg/h 10-60 mcg/h 2-8 mcg/h

R

Lockout (Range) 10 min (6-10 min) 10 min (6-10 min) 5 min (5-10 min) 5 min (5-10 min)

9

Demand Dose 1-2 mg 0.2-0.4 mg 20-50 mcg 4-6 mcg

9

Opioid Morphine Hydromorphone Fentanyl Su entanil

C

TABLE 99-4 Intravenous Patient-Controlled Analgesia Initial Settings

Continuous in usion o opioids is not recommended in the opioid-naïve patient. In patients already receiving opioid medications: (a) I the patient is hospitalized, calculate the patient’s 24-h opioid use and convert this into the IVopioid equivalent, and give 50%-75% o the total dose as the continuous in usion delivered over 24 h and the remaining 25%-50% as demand doses. (b) I the patient is on home oral opioid or transdermal regimen, calculate the patient’s 24-h baseline home regimen into the IVopioid equivalent and administer 75% o this as a continuous in usion and supplement with appropriate demand dose using the initial settings.

doses o ketorolac, ibupro en, or celecoxib may be appropriate. However, this would require consultation with the operative surgeon due to associated bleeding risk and the possibility o impaired bone healing. In the absence o hepatic insuf ciency, scheduled acetaminophen would also be appropriate. One may also consider starting low doses o pregabalin or gabapentin.

Patient controlled analgesia When compared to intermittent bolus dosing o opioids, IVpatientcontrolled analgesia (PCA) o ers signi cantly greater analgesia and satis action. Both the strengths and risks o PCA systems depend upon a negative eedback loop: when in pain, the patient sel administers potent analgesics leading to pain relie , there ore limiting urther opioid demands. An additional bene t o PCA dosing is that the patient is not dependent upon administration variables and has constant access to the prescribed dosing. PCA systems allow or a continuous and demand dosing. Demand dosing is a preset amount that can be accessed at regulated intervals. This dosing also has an hourly maximum dose with lockout to prevent overmedication. Table 99-4 lists common IVPCA programs or initial use with a variety o opioids. As with any opioid-based therapy, PCA use may result in respiratory depression. I there is discordance between nociception (pain) and antinociception (opioid), a relative decrease in pain input or increase in opioid-based inhibition may each result in respiratory depression in the presence o opioids. Minimizing the use o background in usions in opioid-naïve patients mitigates this risk. Background in usions are best individualized to better control the overall pain state when incorporating a home opioid regimen. Home opioid dosing may be converted to background in usion dosing with the addition o patient controlled dosing to assess and treat in the acute pain phase. Once a stable regimen achieves adequate control o the patient’s pain, the dosing requirement may be used to transition to an oral regimen that will re ect the patient’s opioid requirements. Some institutions use pulse oximetry monitoring to assess the respiratory depression associated with opioid administration. Un ortunately, this monitoring is not appropriately sensitive, nor is it in any way speci c enough to capture the relationship between respiratory depression and opioid administration when it is used concomitantly with supplemental oxygen. Pulse oximetry then lends a alse sense o security in addition to monitoring and administrative burden without the bene t o providing predictive value. Capnography, a much more speci c correlate o respiratory depression, is best reserved or those patients who have substantial comorbidities that elevate the risks associated with opioid therapy.

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■ INTERVENTIONAL TECHNIQUES Peripheral nerve blocks Peripheral nerve blocks, either as single injections or continuous in usions o local anesthetic, deliver analgesia and anesthesia around the target nerve. Peripheral nerve blocks may o er superior analgesia, decreased opioid consumption, improved pharmacokinetic titration, and increased patient satis action when compared with systemic analgesic techniques or placebo. Using either land marks, nerve stimulators or ultra sound guided techniques, anesthesiologists may customize the regional anesthetic regimen to re ect each patient’s surgical, perioperative, and rehabilitation requirements. Although single injections o local anesthetic may provide a block lasting up to 24 hours, placement o a perineural catheter through the needle allows the therapy to be extended or up to several weeks. Multiple injections and/or catheters may be needed to adequately anesthetize pertinent nerve distributions. Neuraxial anesthesia Neuraxial anesthesia re ers to injections o local anesthetic and/ or opioids into the epidural or intrathecal space, either through a needle as a single-injection or through an indwelling catheter. Epidural anesthesia: Epidural anesthesia commonly re ers to in u-

sion o solutions containing local anesthetic and opioids through a catheter within the epidural space. As the solution in ltrates this potential space, it spreads superiorly and in eriorly within the spinal canal. This spread gives coverage along dermatomal distribution congruent with the level o the catheter or injectate. This spread is slightly a ected by gravity and patient positioning; thus, patients may notice epidural e ects predominating upon dependent locations when laterally positioned. Epidural solutions commonly contain mixtures o local anesthetic and opioids. High local anesthetic concentrations will result in sympathectomy, sensory loss, and motor block depending upon the required dose or analgesia. In general, the low concentrations o local anesthetic used or analgesia o er a discriminatory block providing excellent analgesia, minimal sensory inhibition and nearly absent motor block. Opioid-only solutions avoid some side e ects such as sympathectomy and motor block, but at the cost o nausea, pruritus, and less-potent analgesia. Solutions combining local anesthetic with opioids provide superior dynamic pain relie , decreased sensory block regression, and decreased local anesthetic dose requirement. Epidural solutions are commonly delivered through continuous in usions rather than single shot administration. While e ective, such in usions ail to account or the dynamic nature o painul conditions. The administration o epidural analgesia using 705

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patient-controlled epidural analgesia (PCEA) systems has become more common. The PCEA system allows the patient to sel administer an epidural bolus at a dose and schedule ordered by the physician, while providing continuous background in usion. Such systems allow or patient-controlled individualization o analgesic regimens. When compared with continual in usion-only regimens, PCEA systems o er lower drug use yet greater patient satis action. Epidural side effects: As with all types o medications, epidural

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analgesia is not without side e ects. Local anesthetics can result in anesthesia, motor blockade, and hypotension rom sympathectomy. When placed in the lumbar and sacral epidural space, local anesthetics or opioids may result in urinary retention necessitating either bladder catheterization or requent bladder scans. The lower-extremity weakness, and potential orthostatic hypotension associated with epidural analgesia, make appropriate all precautions necessary. Sympathectomies due to epidural analgesia may result in pro ound hypotension, although the incidence with postoperative epidural analgesia averages 0.7% to 3.0%. I the epidural is dosed to the upper thoracic dermatomes, blockade o the cardiac accelerator ibers may also lead to severe bradycardia. Frequent hemodynamic monitoring is there ore essential during initiation and modi ication o epidural analgesia involving local anesthetics. Epidural opioid administration is generally devoid o the hemodynamic perturbations seen with epidural local anesthetics. Side e ects are usually those also seen with systemic administration, such as nausea, vomiting, pruritus, and respiratory depression. Pruritus due to neuraxial opioids appears to be related to central activation o “pruritus pathways” that mediate nonhistamine itch. Intravenous naloxone, naltrexone, and nalbuphine each appear ef cacious or treatment o opioid-induced pruritus without a ecting analgesia when dosed appropriately. The rate o respiratory depression rom neuraxial opioids does not appear to di er rom that o systemic opioid administration, ranging rom 0.1% to 0.9%. The concern or respiratory depression stems rom the cephalic spread and systemic distribution o neuraxial opioids. Respiratory depression appears early a ter bolus with lipophilic opioids such as entanyl or su entanil, and may be delayed up to 12 hours with hydrophilic opioids such as morphine. Risk actors include increasing dose, age, concomitant systemic opioid or sedative use, thoracic surgery, prolonged or extensive surgery, and the presence o applicable comorbidities. Parave rte bral ane sthe sia: Occasionally, situations arise in which

a patient would bene it rom epidural analgesia con ined to a single side o the body, or in which an avoidance o large-segment sympatholysis becomes critical. This can be accomplished by delivering local anesthetics to the paravertebral compartment either through a single injection or via continuous in usion via catheter. Such techniques are inding increasing use or unilateral thoracic, breast, abdominal, and hip surgeries, and or pain rom rib ractures. Risks of regional anesthesia As with all medical and surgical therapies, the risk-to-bene t ratios o regional anesthesia should be thoroughly discussed with patients prior to implementation. The American Society o Regional Anesthesia and Pain Medicine (ASRA) published guidelines on providing regional anesthesia or patients on anticoagulation medications. With regional anesthesia there is a rare but catastrophic risk o direct mechanical injury to the spinal cord or peripheral nerves. Bleeding and in ection are likewise possible with any regional anesthetic, especially those related to the central nervous system. With regard 706

to neuraxial and paravertebral analgesia, development o an epidural hematoma may result in spinal cord hypoper usion, injury, and subsequent permanent paralysis. Epidural hematoma ormation may occur during needle or catheter placement, and during catheter removal. Concurrent use o neuraxial or paravertebral analgesia with systemic anticoagulation requires exceptional vigilance to prevent or minimize complications involving epidural hematomas. An epidural hematoma should be considered in a patient with severe back pain or neurologic de cit a ter an epidural placement or removal; this should warrant an immediate imaging and neurosurgical consultation. In ection represents another major concern, especially with neuraxial analgesia. Serious in ections resulting in epidural abscess or meningitis ollowing epidural analgesia are quite rare (65 y

Score No risk = 0 items Risk = ≥1 item

End Points 7-d serious events

Results Validation cohort: Sensitivity: 86%, Speci icity 49% LR(+) 1.7, LR(–) 0.28

No risk = 0 items Risk = ≥1 item

1-mo serious outcome or all cause death

Sensitivity: 90% Speci icity: 70% NPV: 98% LR (+): 3.0, LR (–) 0.15

0-4 (1 point each item)

1-y severe arrhythmias or death

0-4 (1 point each item)

1-y mortality

• Palpitations be ore syncope (+4)

Sum o + and – points

2-y mortality

Score 0: 0% Score 1: 5% Score 2: 16% Score 3 or 4: 27% Score 0: 0% Score 1: 0.6% Score 2: 14% Score 3: 29% Score 4: 53% $22,000 per diagnosis. However, at least one retrospective study suggested that up to 7% o patients with syncope and without chest pain had acute coronary syndrome as the etiology o the syncope. Given their relative low yield, it is important to reserve cardiac enzymes or those patients with intermediate to high pretest probability o coronary disease. Exercise stress testing While exercise testing or syncope evaluation has very low diagnostic yield, such testing can provide value when ordered or speci c indications (Table 101-8). The 2006 ACC/AHA guidelines on syncope management recommend exercise testing in patients with history o coronary artery disease, a ter echocardiography has

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TABLE 101-7 Diagnostic Testing Modalities in Syncope and Estimated Yield

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Test Echocardiography Exercise stress test Carotid sinus massage Tilt-table testing

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Signal-averaged ECG

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Electroencephalogram (EEG) Head computed tomography (CT)

Neurovascular imaging studies (eg, carotid ultrasound)

Indication/Relevant Etiology of Syncope Known or suspected structural heart disease Suspected coronary artery disease or exertional syncope Elderly patients with unexplained syncope or suggestive history Recurrent unexplained syncope a ter structural heart disease excluded or not suspected When negative in patients with low to moderate risk or ventricular arrhythmia, helps exclude this condition in patients with unexplained syncope. Ideal candidates or this test are patients with normal heart structurally, but who unexplained syncope without a prodrome High risk or arrhythmia ( rail, elderly, risk o injury/ all), high suspicion or arrhythmia, or structural heart disease with negative initial workup High suspicion or requent arrhythmia, abnormal ECG, or structural heart disease Frequent syncope (>1 episode/mo) with suspicion or arrhythmia or abnormal ECG/structural heart disease with negative cardiac workup

59% (27% positive, 32% negative)

Negative cardiac workup, in requent syncope, negative tilt examination, negative psychiatric examination. Some role or ILR use a ter initial negative workup

21%

Recurrent unexplained syncope without evidence o structural heart disease or negative cardiac workup, especially with suggestive history Witnessed seizure, postictal state, history o seizure, ocal neurologic signs or symptoms History o head trauma, ocal neurologic indings, or history consistent with seizure

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Electrophysiological study Holter monitoring (test duration: 24-72 h) External loop recorder (test duration: 3-4 wk, or up to 2-3 mo) Implantable loop recorder (ILR, test duration: up to 36 mo) Psychiatric evaluation

Diagnostic Yield 5%-10% 1% 45% in selected monitored population 49% in those without isoproterenol testing Unknown positive yield, but 90% negative predictive value 60% in selected high-risk population 19% (4% positive, 15% negative) 34% (13% positive, 21% negative)

1%-2% 4% in patients with ocal neurologic indings or witnessed seizure Unknown

Signs or symptoms suggestive o transient ischemic attack/stroke; at present no substantial evidence or use o carotid ultrasound or transcranial Doppler in syncope setting

Modi ied and reproduced, with permission, rom Fuster V, O’Rourke RA, Walsh RA, et al. Hurst’s the Heart. 12th ed. New York: McGraw-Hill; 2008. Table 48-5.

assessed or out ow tract obstruction or other contraindication to exercise stress testing. Syncope a ter exercise can be re ex mediated or may represent underlying conduction disease with risk or permanent AV block, as tachycardia can induce a high-grade AV block distal to the AV node. Exercise stress testing is diagnostic when syncope and hemodynamic changes consistent with a syncopal state are reproduced and documented during exercise or when Mobitz II second degree or third degree AV block develop during exercise even without syncope.

TABLE 101-8 Indications for Exercise Stress Testing in the Setting of Syncope • Indications

1. Suspected ischemia 2. Exertion-related syncope 3. Exertion-induced tachyarrhythmias 4. AVB w/BBB (AVB can worsen w/exercise) • Yield: 1% • Echo may be necessary prior to stress testing to exclude structural heart disease (eg, AS, HOCM) AVB, atrioventricular block; AS, aortic stenosis; BBB, bundle branch block; HOCM, hypertrophic cardiomyopathy.

722

Carotid sinus hypersensitivity/syndrome (CSH/CSS) testing CSH is de ned as carotid sinus massage leading to a ventricular pause >3 seconds and/or a decline in systolic BP ≥50 mm Hg without symptoms (or a decline in systolic BP ≥30 mm Hg with symptoms). CSH that produces syncope is classi ed as CSS. CSS occurs more requently in patients >40 years old though is most requent in elderly patients (>70 years). As many patients do not present with a history o neck rotation leading to syncope, CSM should be considered in patients over 40 years old without a clear etiology o syncope. CSM carries a very low rate o neurologic complication (1 minute) recovery state is suggestive o seizure rather than syncope. I seizure is suspected or i there is a provoked attack resulting in a suspected case o psychogenic pseudosyncope or pseudoseizure, an electroencephalogram is an important diagnostic tool. When syncope is the most likely cause, an EEG is usually inappropriate, because interictal EEGs are o ten normal and cannot rule out seizure.

■ ADDITIONAL OUTPATIENT TESTING FOR SYNCOPE Syncope that is recurrent or which is not considered li e threatening a ter 24 to 48 hours o inpatient monitoring can be evaluated sa ely in an outpatient setting. Electrophysiology study Electrophysiology (EP) studies evaluate cardiac conduction and can be help ul in assessing the unction o the AV node and or ventricular or supraventricular arrhythmias. EP studies can identi y intermittent signi cant AV nodal block in patients at risk (eg, bi ascicular block on ECG). In patients with structurally abnormal hearts or those with other symptoms, signs, or testing to suggest ventricular arrhythmia risk, an EP study can help identi y inducible ventricular arrhythmias. EP studies may also identi y supraventricular tachyarrhythmias though this is most o ten only implored in the setting o invasive catheter-based therapy or supraventricular tachyarrhythmias. Head up tilt table testing Head-up tilt-table testing (HUTT) is most use ul in patients with recurrent episodes in which re ex syncope is suspected. Unless there are occupational hazards or a high risk o injury associated with syncope, testing or a single or rare event is not indicated. HUTT may help distinguish syncope rom epilepsy or to help identi y the cause o syncope in the elderly with multiple alls. As re ex syncope can be

C H A P T E R 1 0 1 S y n

Short-term or long-term electrocardiographic monitoring can help establish the diagnosis o arrhythmia as the cause o syncope or help in ruling out arrhythmia. In the patient whose syncope is not li e threatening and in whom a de nitive diagnosis has not been established, outpatient telemetry via Holter monitoring or loop recorders should be considered. In general, Holter recordings are most use ul in patients with daily symptoms o lightheadedness or palpitations, whereas loop recorders are indicated or patients with less requent symptoms.

c

Cerebrovascular event

Holter monitoring, external loop recorders and implantable loop recorders

o

While head trauma and conditions predisposing to increased intracranial pressure (eg, subarachnoid hemorrhage and intracranial neoplasm) can cause transient loss o consciousness, the patient’s history and physical exam will generally identi y neurologic ndings.

p

Trauma and elevated intracranial pressure

situational, the diagnostic utility can be limited. For re ex syncope, a positive study induces transient loss o consciousness in the setting o a vasodepressor and/or cardioinhibitory response. Additionally, the HUTT can be help ul in diagnosing dysautonomia and postural orthostatic tachycardia syndrome. Some protocols use provocative agents (eg, isoproterenol or nitroglycerin) to decrease vascular tone or increase heart rate. These agents increase sensitivity but reduce speci city and reproducibility.

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Neurologic causes o syncope are rare and a more thorough evaluation should be pursued i the initial assessment is suggestive o such an etiology. Dysautonomia can lead to autonomic nervous system ailure in the elderly and should be evaluated as part o the orthostatic hypotension workup (Table 101-3).

Holter monitoring Holter monitoring provides 24 to 72 hours o continuous ECG monitoring via sur ace electrodes at a cost o roughly $1000 per device and associated servicing costs. The yield or a diagnosis o syncope is rom 1% to 4% and negative yield (ie, patients in whom an arrhythmia was not detected during a syncopal event, e ectively ruling out arrhythmia) is near 15%. Holter monitoring carries a very high cost-per-diagnosis ratio due to the in requency o arrhythmia in most patients with syncope o unknown etiology. External loop recorder An external loop recorder, also a portable system with cutaneous electrodes, can be used to retrieve data generated over 3 to 4 weeks and up to 2 to 3 months. External loop recorder continually store and delete ECG data. The patient is able to manually activate the recorder in the setting o symptoms and 5 to 15 minutes o preactivation ECG data is stored or analysis. From prospective studies, the positive yield to achieve diagnosis is approximately 15% to 25%, and the negative yield is approximately 20%, giving this modality also a high cost-per-diagnosis ratio. Patient compliance beyond 3 weeks is unusual and urther limits the use ulness o this test. Implantable loop recorders Implantable loop recorders (ILRs) can provide ECG data up to 36 months and obtain higher diagnostic yield per device than other recording modalities such as the Holter monitor. Implantable loop recorders can have a diagnostic yield o 90% in patients with syncope o unknown etiology though they have a high initial cost more than $10,000. Newer implantable loop recorders are small and can be implanted subcutaneously as an of ce-based procedure with experienced providers. Syncope in the patient with psychiatric illness Antipsychotic medications and side e ects rom chronic use can lead to orthostatic hypotension and/or QT prolongation. Important medications to consider in syncope etiology include benzodiazepines, antidepressants (speci cally SSRIs, tricyclics, and MAOIs), barbiturates, and neuroleptics, as well as drugs o abuse such as ethanol. Pseudosyncope is believed to be a unctional disorder which results in involuntary T-LOC. Patients o ten su er T-LOC though show no signs o seizure during the attack, have a normal EEG, and have normal hemodynamics during a tilt table test. In pseudosyncope, history usually does not identi y a trigger to the event. Attacks occur requently and can last or several minutes—in contrast to 723

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only several seconds o T-LOC seen in true syncope. Psychiatric evaluation is indicated and can be valuable in patients with recurrent syncope without injury or when an exhaustive workup has not yielded a certain diagnosis.

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■ SPECIAL CASE: RECURRENT SYNCOPE

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Regardless o etiology, syncope recurs in 30% to 40% o patients ollowed or 3 years a ter the diagnosis. In patients with vasovagal syncope, prognosis is generally excellent. While age is not predictive o uture risk o recurrence, shortened time to recurrence a ter diagnosis and number o previous syncopal episodes increase recurrence risk. Recurrent syncope does not con er a higher mortality risk than an isolated syncopal episode, but injury morbidity with recurrent episodes may impose restrictions on patient’s quality o li e.

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■ SPECIAL CASE: ELDERLY PATIENTS WITH SYNCOPE

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Elderly patients o ten have coexistence o many predisposing medical conditions that can lead to syncope. Common causes in the elderly population include orthostatic hypotension, re ex syncope, carotid sinus syndrome, and arrhythmias. Syncope o cardiac origin carries a similar mortality risk in both young and old. As in all patients, a detailed but ocused history and physical examination can yield a diagnosis in many initial evaluations. A comprehensive medication history ocusing on temporal relationships between the alls/syncope and initiation o new medications or dosing changes is critical, as is consideration o changing drug levels due to dynamic renal or hepatic unction. Any associated comorbidities such as deconditioning, dependence or activities o daily living, cognitive impairment, and per ormance status can also increase risk. A ocused neurologic examination should be complemented by assessment o gait instability, orthostatic challenge, and balance. Routine carotid sinus massage (Figure 101-3) (when no contraindications) is recommended or elderly patients presenting with syncope in addition to the thorough initial assessment as used or younger patients.

PRACTICE POINT

•

A high-yield approach at initial evaluation involves a thorough history; medication review; physical examination ocused on postural blood pressure measurement, cardiac, and neurologic examinations; and electrocardiogram. Risk strati cation should be carried out on initial evaluation in accordance with wellvalidated risk-scoring tools. In those with an unclear etiology, urther testing should be done with a ocus on ef ciency and high-yield tools.

TREATMENT AND PRIMARY PREVENTION OF SYNCOPE

■ TREATMENT OVERVIEW Treatment o syncope is directed at the underlying disorder causing the episode. Detailed discussion o those therapies is beyond the scope o this chapter; however, some generic principles are relevant to inpatient practice. Irrespective o establishing an etiology or syncope, the primary goals in the treatment o syncope are to reduce the risk o injury/trauma, improve survival, and evaluate and prevent recurrent syncopal events. Treatment is aimed at an underlying cause i one can be identi ed (Figure 101-4).

■ REFLEX SYNCOPE, AUTONOMIC DYSFUNCTION, AND ORTHOSTATIC HYPOTENSION/INTOLERANCE In re ex/vasovagal syncope or autonomic dys unction and consequent orthostatic hypotension, the aim is to prevent syncope 724

recurrence and limit risk o bodily injury or harm to the patient. Treatment o re ex syncope includes patient education, reassurance, and avoidance o triggers. Recognition o triggers and recognition o a prodrome warning period, such as nausea, lightheadedness, and sense o impending all or loss o balance can help abort a syncopal event. Physical counter-pressure maneuvers (PCMS) to increase venous return can be instituted with success i done in a timely manner during prodrome or trigger recognition. These maneuvers involve causing a rapid increase in systolic and diastolic blood pressure through the timely initiation o either gluteal muscle tightening with concomitant leg crossing or arm tensing through interlocking handgrip and isometric contraction. In a multicenter, prospective trial, the burden o recurrent syncope enjoyed a relative risk reduction o near 40% when comparing patients who had received physical counterpressure maneuver training with those who did not. Pharmacologic therapy or prevention and treatment o re ex syncope address peripheral vasoconstriction, volume expansion, prevention o paradoxical bradycardia and excess vagal activity, and treatment o anxiety (Table 101-9). No randomized controlled trial evidence establishes bene t o these therapies, and none o the medications commonly used or re ex syncope has Food and Drug Administration approval or this indication. Treatment o orthostatic hypotension and intolerance should rst seek to employ nonpharmacologic measures. Patients should change posture slowly, increase uid and salt intake to 3 L and up to 10 g sodium per day i supine hypertension is not a comorbid illness, seek adjustment o antihypertensives with physician guidance, and avoid excessive durations o recumbency and sleep, while maintaining the head o the bed at 10° to 20°. Avoiding the rapid ingestion o cold water, limiting the size o meals and carbohydrate intake, and avoidance o alcohol help reduce postprandial hypotension. The use o tight lower-extremity elastic stockings and occasionally abdominal binders can help maintain venous return while standing. Finally, as in re ex syncope, all patients should be counseled on anticipatory physical counterpressure maneuvers. Pharmacologic measures or OH treatment are aimed at expanding central volume, improving vasoconstriction, and mitigating various actors such as anemia, nocturnal diuresis, and poor sympathetic tone (Table 101-9).

■ ARRHYTHMIAS Speci c to the nature o the arrhythmia, treatment o syncope due to arrhythmia varies rom medication discontinuation to cardiac pacemaker or implanted cardioverter-de brillator placement and even radio requency catheter ablation. See Chapter 132 (Supraventricular Tachyarrhythmias), Chapter 133 (Bradyarrhythmias), and Chapter 134 (Ventricular Arrhythmias) or more detailed in ormation about treatment o related speci c diagnoses that may lead to syncope. See Chapter 136 (Pacemakers, De brillators, and Cardiac Resynchronization Devices) or speci c in ormation regarding indications or those devices in relationship to syncope or arrhythmias. Implanted pacemakers or ICDs can be associated with syncope. When suspected, device interrogation by a device specialist or trained cardiologist is help ul. In the setting o generator battery depletion or lead ailure, device replacement is e ective. ICDs may rarely be associated with syncope i the patient su ers an arrhythmia and loss o consciousness outside o the speci c treatment thresholds set or the device. For example, a patient with ventricular tachycardia may su er loss o consciousness be ore appropriate therapy i delivered. Reprogramming and/or the addition o antiarrhythmic medications may be necessary in this setting, in consultation with cardiology or electrophysiology specialists.

C H A P T E R 1 0 1 S y n c o p e

Figure 101 3 Carotid sinus massage methodology. A. Contraindications: MI, TIA, or CVA in the past 3 months; history o VT or VF, or previous adverse reaction to carotid sinus massage (CSM). B. Relative contraindications: carotid bruits require carotid ultrasound; i signi cant stenosis is present some recommend per orming the CSM while the patient is supine. Others recommend against per orming it. C. With the patient supine (at least 5 minutes), 1. Record baseline ECG, SBP, DBP, HR. 2. Per orm CSM on the right side while patient is supine. Another operator should record hemodynamic variable changes. Carotid sinus is located midway between the thyroid cartilage and angle o mandible; rm longitudinal massage on area o maximal carotid artery pulsation is carried out or at least 5 seconds. 3. During CSM or 5 seconds, the operator per orming massage should indicate “CSM ON” and “CSM OFF” to indicate those time points on continuous ECG recording, done by the second operator. 4. Nadir SBP and DBP occur typically 15 seconds a ter stopping CSM. CSM should be discontinued i a sinus pause >3 seconds occurs. In the case o prolonged asystole, a precordial “thump” is advised. 5. Repeat the procedure in the le t supine, right erect, and le t erect, only a ter patient’s HR has reached pre-CSM levels in each case. Upright position CSM has an additional 30% diagnostic yield. 6. I neurological complications arise, lay the patient supine, ensure BP is returned to baseline as soon as possible, give aspirin 325 mg i not contraindicated, and admit or observation. CSM, carotid sinus massage; CVA, cerebrovascular accident; DBP, diastolic blood pressure; ECG, electrocardiogram; HR, heart rate; MI, myocardial in arction; SBP, systolic blood pressure; TIA, transient ischemic attach; VF, ventricular brillation; VT, ventricular tachycardia. (Reproduced, with permission, rom Halter JB, Ouslander JG, Tinetti ME, et al. Hazzard’s Geriatric Medicine and Gerontology, 6th ed. New York: McGraw-Hill; 2009. Fig. 57-4.)

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Re a s s ura nce, life s tyle modifica tions

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S pe cific the ra py for s tructura l he a rt dis e a s e ; ICD impla nta tion for morta lity be ne fit in s e le ct pa tie nts a t high ris k

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Figure 101 4 Proposed inpatient algorithm or hospitalist management o syncope.

TABLE 101-9 Selected Therapies for Reflex Syncope and Orthostatic Hypotension Treatment Reconditioning

Application Aerobic exercise 20 min 3 times/wk

Form Effective in NCS PD HA OH X X X X

Physical maneuvers (tilt training, etc) Sleeping with head tilted upright Hydration Salt Fludrocortisone

30 min 3 times per day

X

During sleep

X

2 L orally per day 2-4 g/d 0.1-0.2 mg orally per day

X X X

Metoprolol Labetalol Midodrine

25-100 mg twice a day 100-200 mg orally twice a day 5-10 mg orally three times a day

Methylphenidate Bupropion Clonidine Pyridostigmine SSRI-escitalopram

5-10 mg orally three times a day 150-300 mg XL every day 0.1-0.3 mg orally twice a day 30-60 mg orally per day 10 mg orally per day

Erythropoietin

10,000-20,000 g subcutaneously every week 50-200 µgm SC three times a day

Octreotide Permanent pacing

X X X X

Problems I done too vigorously may worsen symptoms Noncompliance is common

X X X X

X

X X

X X

X

X

X

Edema Edema Hypokalemia, hypomagnesemia, edema Fatigue Fatigue Nausea, scalp itching, supine hypertension Anorexia, insomnia, dependency Tremor, agitation, insomnia Dry mouth, blurred vision Nausea, diarrhea Tremor, agitation, sexual problems Pain at injection site, expensive

X

Nausea, diarrhea, gallstone

X X X

X

X

X X

X

X X X X

X

X

X

HA, hyperadrenic postural orthostatic tachycardia syndrome; NCS, neurocardiogenic syncope; OH, orthostatic hypotension; PD, partial dysautonomia postural orthostatic tachycardia syndrome; SSRI, selective serotonin reuptake inhibitor.

726

CONSULTATION Hospitalists should rely on their consultant colleagues when there is a therapeutic aim to address by the approached specialty. A particularly use ul result o the rugal use o consultation is deciding with the consultant whether the patient needs urther inpatient testing or treatment and whether outpatient ollow-up is suf cient or an otherwise stable condition. Inpatient cardiology consultation or diagnostic or therapeutic testing or interventions (eg, cardiac catheterization, tilt-table testing, carotid sinus massage, or electrophysiology study) may each be appropriate based on the clinical context o the syncope. The routine use o neurologic testing in the initial evaluation o syncope in the absence o neurologic symptoms has poor diagnostic value and cost e ectiveness. Presentation suggesting vertebrobasilar insuf ciency may require neurology consultation, as would suspected seizure as etiology o unwitnessed syncope (especially i EEG or continuous EEG monitoring is believed indicated). Consultation with a psychiatrist is indicated to identi y psychosomatic conditions predisposing to syncope, such as conversion, somato orm, or actitious disorder. Establishing psychogenic pseudosyncope or another psychiatric diagnosis as syncope etiology may be use ul in patients with recurrent symptomatic syncope who have undergone a thorough negative workup or cardiac, re ex, and orthostatic syncope as appropriate.

C H A P T E R 1 0 1 S y n c o

QUALITY IMPROVEMENT TO ADDRESS PERFORMANCE GAPS

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The primary aims in treating patients with structural heart disease are to identi y the causative actor contributing to syncope and treat the primary process as well as to prevent sudden cardiac death. History is important as patients with underlying heart disease o ten have re ex and orthostatic syncope. Surgical therapy is indicated in the setting o syncope due to severe aortic stenosis or atrial myoxoma. Syncope in the setting o acute coronary syndrome, pulmonary embolism, or pericardial tamponade requires urgent condition-speci c therapy. Patients with syncope due to underlying restrictive cardiomyopathy or severe pulmonary hypertension require symptomatic management which o ten cannot correct the underlying pathology. Syncope with hypertrophic cardiomyopathy requires arrhythmia speci c therapy (o ten with medications) and consideration o an ICD or prevention o SCD. See Chapter 128 (Acute Coronary Syndromes), Chapter 130 (Myocarditis, Pericardial Disease, and Cardiac Tamponade), and Chapter 131 (Valvular Heart Disease) or management o speci c related disorders that could lead to syncope. Placement o an ICD has been established to prevent SCD in patients with (a) ischemic and nonischemic cardiomyopathy with severely reduced systolic unction, (b) hypertrophic cardiomyopathy, (c) arrhythmogenic right ventricular cardiomyopathy, and (d) patients with primary electrical abnormalities (eg, long QT and Brugada syndromes).

unexplained syncope occurs while driving and/or in the presence o structural heart disease, driving limitations may be necessary or legally required. For pro essional drivers, permanent restrictions may be recommended i an ICD has been implanted, occasional syncope occurs during high-risk activity, syncope is recurrent and severe and treatment has not been established, and in unexplained syncope i treatment has not been established. Long-term accident and insurance data indicate, reassuringly, that rates o vehicular accidents are no higher than in the general population without syncope. Timely ollow-up with appropriate outpatient physicians (primary care physicians, cardiologists, neurologists, as indicated) should occur within 2 to 4 weeks o hospital discharge.

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■ STRUCTURAL HEART DISEASE MANAGEMENT

One o the major areas o practice improvement related to syncope is resource utilization. Patients with syncope require a multidisciplinary approach in some cases and in other instances may be discharged sa ely rom the emergency department or hospital with close ollow-up. In the United States, up to 1% o all ED patients present with syncope, with 32% admitted representing 2% o all ED admissions. This equates to >740,000 ED visits per year and >460,000 hospital admissions annually. With median cost o each US hospital admission or syncope o approximately $8700, it comes as no surprise that our annual expenditure or syncope is approximately $3.8 billion. Hospitalists are keenly positioned to appreciate costs associated with syncope admissions and the bene ts reaped by thought ul resource utilization. Patients should be risk strati ed using well-validated criteria, and urther testing carried out to assess posthospital risk or injury and mortality. Early discharge rom the ED or hospital should be considered in low-risk patients. Testing should be limited to that necessary or immediate risk strati cation and/or diagnosis con rmation or treatments o the syncopal event. In a retrospective analysis o costs associated with inpatient admission o syncope in elderly patients, researchers ound that postural blood pressure recording (ie, orthostatics measurement) costs $17 per test a ecting the diagnosis or management o a case o syncope. In contrast, the cost e ectiveness o cardiac enzyme measurement was $22,397, head CT $24,881, ECG $1020, and telemetry $710 per clinically relevant nding a ecting diagnosis or treatment (Table 101-10). Three societies, The American College o Physicians (ACP), the American Academy o Neurology (AAN), and the American College o Emergency Physicians (ACEP) have identi ed overtesting in simple syncope as a key area o opportunity to reduce waste in health care, as part o the American Board o Internal Medicine (ABIM) Choosing Wisely® campaign. All three organizations suggest reduction o neurologic imaging in patients presenting with

TABLE 101-10 Test Value and Cost in Syncope Patients DISCHARGE PLANNING Prior to discharge, patients should be educated on measures to prevent recurrent re ex syncope, recognition o prodromal symptoms, and warning signs that warrant emergency care. O particular concern to patients is the ear o syncope recurrence while driving. Driving ollowing a syncopal episode is regulated by individual states, and clinicians should re er to their speci c state laws when making recommendations to patients, and clinicians should document clearly discussions with patients regarding driving ollowing syncope. However, in general, private drivers usually have no restrictions on driving independent o those imposed by having an ICD according to current society guidelines. I , however,

Test Postural BP EKG Echo Carotid U/S CVenzymes Head CT EEG

% Patients Receiving Test 38% 99% 39% 13% 95% 63% 8%

% Patients Diagnosis Affected by Test 26% 7% 4% 1% 2% 2% 1%

Cost per Diagnosis or Management $17 $1020 $6272 $19,600 $22,400 $25,000 $33,000

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“simple” syncope, where patients do not have ocal or speci c neurologic ndings based on history or physical examination to suggest a neurologic etiology. The recommendations have a basis in clinical studies analyzing syncope testing patterns, diagnostic yields, and costs. Such studies consistently show low diagnostic impact at high cost i such tests are conducted indiscriminately in syncope patients. By ollowing these recommendations, hospitalists can help reduce the unnecessary use o brain imaging and carotid imaging in patients presenting with syncope. Judicious use o testing will improve the diagnostic yield o tests ordered, without reducing the relevant diagnosis o neurologic etiologies o syncope. This practice is summarized in the UK’s National Institute or Health and Clinical Excellence guidelines or transient loss o consciousness. Admission or the syncopal patient should not be unnecessarily prolonged. On the part o the hospitalist as coordinator o care, this may require earlier consultation with specialists to plan earlier testing, discharge, and ollow-up. In prospective, randomized controlled trials incorporating strict adherence to syncope criteria or admission and utilization o Syncope Management Units (SMU) in the ED to triage syncope patients, there is a marked reduction o hospital length o stay, number o tests conducted per patient, and associated lower costs. SMUs involve staf ng by ED physicians, cardiologists, and/or neurologists and ready access to echocardiogram, tilt testing, beatto-beat blood pressure, and continuous telemetry monitoring or up to 6 hours with a decision reached to admit or discharge in that time rame. Long-term ollow-up to 2 years has shown no di erence in morbidity and mortality in these patients. With care ul selection, triage, and early discharge, hospitalists can make a lasting impact on the resources utilized in the management o syncope. CONCLUSION Syncope is characterized by sudden, transient, reversible loss o consciousness with prompt spontaneous recovery. Recurrent syncope can be distressing to the patient, carries a serious risk o bodily injury and harm, and can lead to signi cant li estyle changes including loss o gain ul employment. Diagnosis should occur in a timely, costef cient manner. At the time o discharge, the goal is to provide the patient with a reasonably con dent estimate o prognosis, risk o recurrence, and goals and timing o urther diagnostic studies and therapy. A high-yield approach at initial evaluation involves a thorough history; medication review; physical examination ocused on postural blood pressure measurement, cardiac, and neurologic examinations; and electrocardiogram. In those with an unclear etiology, urther testing should ocus on ef cient and high-yield tools based on the thorough history and physical examination. Risk strati cation

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should be carried out on initial evaluation in accordance with wellvalidated risk-scoring tools (Table 101-5). Speci c causes o syncope such as arrhythmias and structural cardiopulmonary disease should be quickly identi ed and treated in consultation with a specialist to expedite care as well as to establish adequate, timely ollow-up a ter hospital discharge. Finally, an area o active research in syncope is the use o SMUs, primarily in emergency departments. Success in Europe is the basis or ongoing investment o this concept in the United States. SMUs can help identi y patients who would otherwise be deemed low risk by standardized triage protocols and discharged rom the emergency department or rapid ollow-up. ACKNOWLEDGMENT Special thanks to Robert Young, MD or his contributions to the rst edition chapter.

SUGGESTED READINGS Cooper PN, Westby M, Pitcher DW, Bullock I. Synopsis o the National Institute or Health and Clinical Excellence Guideline or management o transient loss o consciousness. Ann Intern Med. 2011;155:543-549. Mendu ML, McAvay G, Lampert R, Stoehr J, Tinetti ME. Yield o diagnostic tests in evaluating syncopal episodes in older patients. Arch Intern Med. 2009;169(14):1299-1305. Moya A, Sutton R, Ammirati F. Guidelines or the diagnosis and management o syncope (version 2009). The Task Force or the Diagnosis and Management o Syncope o the European Society o Cardiology (ESC). European Heart Journal. 2009;30:2631-2671. Reed MJ, Newby DE, Coull AJ, Prescott RJ, Jacques KG, Gray AJ. The ROSE (Risk Strati cation o Syncope in the Emergency Department) study. J Am Coll Cardiol. 2010;55:713-721. Schnipper J, Kapoor W. Diagnostic evaluation and management o patients with syncope. Med Clin N Amer. 2001;85(2):423-456. Serrano LA, Hess EP, Bellolio MF, et al. Accuracy and quality o clinical decision rules or syncope in the emergency department: a systematic review and meta-analysis. Ann Emerg Med. 2010;56:363-373. Soteriades ES, Evans JC, Larson MG, et al. Incidence and prognosis o syncope. N Engl J Med. 2002;347:878-885. Sun BC. Quality-o -li e, health service use, and costs associated with syncope. Prog Cardiovasc Dis. 2013;55:370-375.

102

CHAP TER

Tachycardia Geof rey L. Southmayd, MD

Key Clinical Questions 1

How do you triage a patient with a new tachyarrhythmia?

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What are the electrocardiographic eatures that suggest that a wide complex tachyarrhythmia is o ventricular origin?

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What are the electrocardiographic eatures that suggest that a wide complex tachyarrhythmia is o supraventricular origin?

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What is the di erential diagnosis or short RP tachycardia? What is the di erential diagnosis or long RP tachycardia?

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How do you acutely manage a symptomatic tachyarrhythmia?

INTRODUCTION This chapter will review the initial bedside approach to a hospitalized patient with a new, potentially li e-threatening tachycardia, de ned as a heart rate ≥100 beats per minute (bpm). The reader is then re erred to subsequent cardiology chapters or de nitive management o speci c arrhythmias.

■ THE NORMAL CARDIAC CONDUCTION SYSTEM The conduction pathway in the heart begins in the sinoatrial node, which spontaneously activates the right atrium, the interatrial septum, and then the le t atrium. The initial portion o the P wave represents depolarization o the right atrium, and the terminal portion depolarization o the le t atrium. Normally, the atrioventricular (AV) node, His bundle, and bundle branches transmit impulses in anterograde ashion rom the atria to the ventricles. The QRS complex represents ventricular depolarization and the T wave represents ventricular repolarization (Figure 102-1).

■ TACHYARRHYTHMIAS AND CONDUCTION DISTURBANCES Tachycardias are encountered requently in inpatient practice. Symptoms rom tachyarrhythmias are variable, and some patients are asymptomatic. When present, symptoms may include palpitations, shortness o breath, chest pain, anxiety, syncope, hypotension, or may mani est by hemodynamic collapse and sudden cardiac death. In addition to the typical AV conducting pathway, anomalous bands o tissue—accessory pathways—may be able to conduct between the atria and ventricles in a retrograde or antegrade ashion that bypasses the normal conduction system. These pathways may or may not be visible on sur ace electrocardiogram (ECG). Supraventricular tachycardias (SVTs) include all tachycardias that arise at or above the His bundle. Sinus tachycardia is easily the most common SVT, but does not represent a primary pathologic arrhythmia except in rare cases. Paroxysmal SVTs usually have narrow complexes with a normal QRS duration o 0.1 second in any precordial RS lead; (3) presence o AVdissociation, usion, or capture beats; and (4) morphology criteria or VT present in both leads V1 and V6. I none o these criteria are met, the diagnosis avors supraventricular tachycardia with aberration.

The presence o atrioventricular (AV) dissociation, usion beats, and capture complexes generally avor the diagnosis o VT. AV

dissociation is characterized by loss o dependence between atrial and ventricular depolarization, and is identi ed when the P waves “march” through the tachycardic sequence without any temporal relationship to QRS complexes. In these cases, the ventricular rate should be greater than or equal to the atrial rate. When present, AVdissociation is highly speci c or VT, but recognition o P waves on the sur ace ECG during VT may be challenging. P waves are absent in up to 70% o VT cases, and so their absence should not reassure the examiner that the arrhythmia is supraventricular in origin (Figure 102-3). Fusion beats, arising rom simultaneous activation o the ventricle rom two sources, have a QRS con iguration that is intermediate between supraventricular and ventricular complexes. They orm when the ventricle is depolarized simultaneously via the normal conduction system in addition to a ventricular ocus. Similarly, capture beats are ormed when a sinus nodal impulse success ully conducts down to the ventricles in the typical manner, resulting in a QRS complex that is identical to the baseline ECG (Figure 102-4).

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Figure 102 4 Capture complex (above) and fusion beats (below, arrows). 731

TABLE 102-1 Likelihood o VT Versus SVT with Aberrancy SVT with Aberrancy More Likely… Hemodynamic stability Patients with normal hearts Narrow QRS Similar QRS morphology to QRS during normal sinus rhythm or during an aberrantly conducted PAC Presence o P waves Typical bundle branch block (140 ms supports the diagnosis o VT, especially i associated with northwest axis (–90° to +180°) o the QRS complex in the rontal plane. This is due to a shi t in depolarization vector rom cardiac apex toward the base. Similarly, the precordial leads V4-V6 would be expected to have negative QRS complexes. See Chapter 134 (Ventricular Arrhythmias). Activation o the ventricles by SVT over an accessory pathway generally results in less extreme rontal axis deviation, and predominantly positive QRS complexes in the lateral precordial leads (Table 102-1).

■ WHAT IS THE RATE? In patients with SVT, atrial rates (measured using the P-P interval) and ventricular rates (measured using the R-R interval) may di er due to limitations o AV nodal conduction, and rate evaluation may provide use ul clues to the etiology o the tachyarrhythmia. In cases o typical atrial utter (AFL), atrial rates average near 300 bpm (range 240-340 bpm) due to a common macroreentrant circuit around the tricuspid valve. See Chapter 132 (Supraventricular Tachyarrhythimias). ECG typically shows classic “sawtooth” utter waves that are predominantly negative ( or counterclockwise type 1 AFL, most common) or positive ( or clockwise type I AFL) in the in erior leads. With 2:1 AVnodal conduction, the ventricular rate alls to around 150 bpm (Figure 102-5). Frequently, utter waves are buried within the T waves, and can be dif cult to distinguish rom other SVTs. Recognition o a ventricular rate near 150 bpm should raise the clinician’s pretest probability or AFL unless an alternate diagnosis is evident. In these cases, vagal maneuvers or adenosine may be use ul to slow the ventricular rate and identi y the underlying atrial rhythm. In cases o variable AV block, the ventricular rate will appear irregular. It is sometimes helpul to look or discrete R-R intervals that have a common divisor; or example, a rate o 150 bpm or some sequences and 100 bpm or others is consistent with AFL with variable block (2:1 and 3:1 with a stable atrial rate o 300 bpm) (Figure 102-6). Type II AFL has aster atrial rates in the range o 340 to 440 bpm, and may not demonstrate sawtooth pattern on ECG.

Sinus tachycardia classically has a maximum rate o 220 bpm minus the patient’s age in years. Multi ocal atrial tachycardia (MAT) more o ten occurs at rates between 100 and 150 bpm, and atrioventricular nodal reentry tachycardia (AVNRT) and atrioventricular reentrant tachycardia (AVRT) typically range rom 150 to 250 bpm (Figure 102-7).

■ IS THE RHYTHM REGULAR OR IRREGULAR? Regularity is de ned by beat-to-beat variation in rate that does not exceed 10%, although most regular rhythms demonstrate even less variability. Sinus tachycardia, AFL with consistent AV conduction, AVNRT, AVRT, and atrial tachycardia cause regular tachyarrhythmias. In contrast, AF, MAT, and tachyarrhythmias due to multiple anterograde AV nodal pathways cause irregularly irregular rhythms (Figures 102-8 and 102-9). MAT may be distinguished rom sinus tachycardia with requent multi ocal atrial premature complexes because it does not have any dominant atrial pacemaker. MAT is identi ed by ectopic P waves o at least three morphologies best seen in leads II, III, and V1, a ventricular rate o >100 bpm, isoelectric baseline between P waves, and varying PP, PR, and RR intervals. Some P waves may be blocked due to their rapid rate. Atrial tachycardias with variable AVblock may also appear irregular. VT and SVT with aberrancy are typically regular orms o WCT. Monomorphic VT can occasionally produce slight irregularity, most commonly in the period immediately a ter onset (the so called “warm-up phenomenon”). An irregular WCT is more suggestive o polymorphic VT or AF with aberrant conduction (Table 102-2).

■ EXAMINATION OF P WAVES Are P waves present during the tachyarrhythmia? What is the P wave morphology, and how do they compare with the baseline sinus ECG? The next step is to identi y the presence o atrial activity and to examine the relationship between the P wave and the QRS complex. P waves may be embedded at the end o the QRS complexes or

ll Figure 102 5 A macroreentrant circuit in the right atrium causes atrial flutter “sawtooth” waveforms accompanied by an atrial rate that varies between 240 and 340 bpm. 732

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Figure 102 6 Type 1 aflutter with variable block.

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Figure 102 7 Anarrow QRS complex tachycardia in the range of 150 to 250 beats/min, often with P waves inscribed at the terminal portion of the QRS complex and reflecting retrograde atrial depolarization.

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Figure 102 8 An irregularly irregular narrow complex tachycardia consistent with atrial fibrillation.

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Figure 102 9 MAT. 733

Rhythm Sinus Tachycardia

ECG Features Regular narrow complex rhythm, normal P wave axis; Ventricular rate up to 220 minus the patient’s age

Uni ocal Atrial Tachycardia

Regular rhythm with atrial rate 150-250 bpm; Single nonsinus P wave morphology; Ventricular rate >100 bpm.

Multi ocal Atrial Tachycardia (MAT)

Rate 100-150 bpm, Irregularly irregular rhythm; P waves with at least three di erent morphologies; varying PR, RR, RP intervals Atrial rate o 240-340 bpm usually with 2:1 AVblock; QRS may be normal or aberrant; rate and regularity depend on AVconduction

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TABLE 102-2 Tachyarrythmias

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AV-Nodal Reentrant Tachycardia (AVNRT)

Usually underlying disease present (heart or lung); i no underlying cardiopulmonary disease, rule out thyroid disease or PE Absent P waves; Atrial Atrial enlargement due activity irregular with varying to any cause including ibrillatory waves; Ventricular structural heart disease rate o 130-200 bpm, irregularly or CAD; lung disease, irregular rhythm hyperthyroidism, low Mg ++, alcoholism, I rate >200 bpm and QRS cocaine, physiologic >0.12 s varying in width, stress consider WPW Rate 150-250. P waves o ten None. Most common hidden, but when present SVT (>60%) are retrograde near terminal portion o QRS. RP interval is short (typical AVNRT) or long (atypical AVNRT)

AVReentrant Tachycardia (AVRT)

Rate 150-250 Orthodromic: narrow complex, retrograde P waves with short RP interval Antidromic: wide complex, retrograde P waves with long RP interval

None

WPW

Most patients asymptomatic with no dysrhythmias; Short PR interval and delta wave present with widening o QRS. May be associated with AVRT, AFL, AF, and VT/VF Three or more PVCs at a rate >100/min in rapid succession; RR intervals usually regular; AVdissociation, capture and usion beats, extreme axis deviation, atypical bundle branch block, prolonged QT interval; abrupt onset and end

Congenital (Ebstein anomaly) and acquired

Ventricular Tachycardia

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Predisposing Conditions Underlying disorder, hypermetabolic state or systemic stressor (anemia, ever, hypovolemia), drug e ect Uncommon; cardiopulmonary disease, drugs, status post AF ablation, digitalis intoxication Acute illness, cardiopulmonary disease, sepsis, low K+ and Mg ++

Structural heart disease; hemodynamic instability or cardiac compromise

Electrical Physiology Sinus node the one dominant atrial pacemaker; Rapid narrow complexes usually similar to patient’s baseline; PR interval may be short, normal, or prolonged Ectopic atrial ocus—either rom enhanced automaticity or reentry; Paroxysmal i reentrant mechanism; incessant i enhanced automaticity Enhanced automaticity; MAT does not require AVconduction and may persist during AVblock

Most cases due to reentry around tricuspid valve

Initial Management Treat underlying problem

Adenosine terminates rhythm in 60%-80% o cases. Rate control with AVnodal blockade Treat underlying illness; replete K+ and Mg ++; rate control; digoxin o no value; cardioversion ine ective Electrical cardioversion i hemodynamically unstable; vagal maneuvers slow rate and expose lutter waves

Increased automaticity and multiple reentrant wavelets predominantly in the le t atrium around the pulmonary veins; ventricular rate may regularize in digitalis toxicity but atrial activity remains totally irregular

Rate control with AVnodal blockers; electrical cardioversion i unstable

Reentry circuit con ined to AVnode, with antegrade conduction down slow pathway and retrograde via ast pathway (typical, 80%-90%) or antegrade via ast pathway and retrograde via slow (atypical, 10%-20%) Reentry circuit involving accessory pathway Orthodromic: antegrade conduction via AVnode, retrograde conduction via accessory pathway Antidromic: antegrade conduction via accessory pathway, retrograde via AVnode Accessory pathway (Kent bundle) bypasses the AVnode and causes pre-excitation o ventricle (delta wave)

Usually terminates with vagal maneuvers or adenosine

Brugada criteria: AVdissociation; RS complex absent in V1-V6; R to S interval >100 ms in any precordial lead; morphology criteria or VT in V1-V2 and V6

Orthodromic: terminates with vagal maneuvers and adenosine Antidromic: Caution with AVnodal blockade. Expert consultation. Electrical cardioversion or unstable patient Electrical cardioversion i hemodynamic instability; ventricular rates >285 at greatest risk o degenerating to VF Electrical cardioversion or hemodynamic instability; Antiarrhythmic therapy or stable patients

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Figure 102 10 Atrial tachycardia is characterized by a P-wave axis or morphology that is distinct from that of sinus rhythm, generally 150 to 250 beats/min, characteristically slower than that of atrial flutter.

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within the T wave; there ore, it is important to compare the tracing to prior ECGs to examine or changes in the QRS and T wave morphology. The normal sinus P wave is 0.08 to 0.11 seconds in duration and is always upright in leads I and II and negative in lead aVR. It is usually upright in lead aVF. Due to the location o the sinus node in the superior right atrium, the atrial depolarization vector rst moves anteriorly to the right atrial tissue, and then posteriorly toward the le t atrium. As a result, the P wave is usually biphasic in leads V1 and V2, positive in V3-V6, and may appear notched in the limb leads. Leads II and V1 are the most help ul places to assess P wave morphology. Ectopic atrial rhythms may have upright P waves arising rom an atrial ocus near the sinus node or inverted P waves arising rom an ectopic ocus in the lower atrium. The location o the ectopic ocus relative to the AV conduction system and the presence or absence o delay in this system determines the duration o the PR interval (whether short, normal, or prolonged). The QT interval (representing the duration o ventricular depolarization and repolarization) is typically normal in ectopic rhythms. Ectopic P waves will have a di erent morphology rom sinus P waves and may be easier to identi y i there is an earlier ECG tracing o sinus rhythm used as a re erence. P waves that are negative in aVL or terminally positive in V1 suggest a le t atrial ectopic ocus. Negative P waves in the in erior leads are seen in AVNRT and AVRT, as well as atrial tachycardias that originate in the lower atrium. When ectopic P waves precede each QRS complex (even i the QRS complex is wide) then the tachycardia is supraventricular in origin. This is the case even when P waves are retrograde (inverted in lead II and upright in lead aVR), as would be seen in the setting o low atrial tachycardia. When ectopic P waves ollow the QRS complexes, the origin o the tachyarrhythmia may be either supraventricular rom the AVjunction or ventricular. Tachycardia arising rom the AVnode more commonly has narrow QRS complexes, although AVjunctional tachycardia may be associated with aberrant conduction causing a wide QRS complex tachycardia.

abnormal. AVblock may occur without interrupting the tachycardia because the AVnode is not an integral part o the arrhythmia circuit. An ectopic atrial tachycardia with 2:1 block may be identi ed by nding a second P wave buried in the terminal portion o the QRS complex in the in erior leads. In this case, measurement o the timing o de ections will demonstrate that they occur exactly hal way between the more visible P waves (Figure 102-10). Suspect digitalis intoxication i paroxysmal tachycardia is associated with AVblock. Unlike sinus tachycardia, AFL and atrial tachycardias, the mechanisms o AVNRT and AVRT involve reentrant circuits within the AV node ( or AVNRT) or via an accessory pathway ( or AVRT). On ECG, AVNRT and orthodromic AVRT can be recognized by narrow complex, short R-P interval tachycardia. In many cases, these rhythms will appear without evident P waves, but i they are visible, P waves appear at the terminal portion o the QRS complex or superimposed on the ST segment or T wave, re ecting retrograde atrial depolarization. See Chapter 132 (Supraventricular Tachyarrhythmias). Di erentiation between AVNRT and AVRT is o ten impossible by sur ace EKG alone, and may require electrophysiological evaluation. AVNRT is much more common than AVRT (Figure 102-11 and Table 102-3).

CASE 102-1 (continued) POSTOPERATIVE TACHYCARDIA Per OR notes: In the operating room, the patient received 4 L o IV uids with no intraoperative hypotension or tachycardia. Estimated blood loss was approximately 1 L. Subsequently, in the

If P waves are present, what is the R P interval? Together with the P wave morphology, the R-P interval can assist distinguishing various causes o SVT. Long R-P tachycardia is de ned by an R-P interval that is longer than hal the R-R interval. Sinus tachycardia is a long R-P tachycardia. By de nition, sinus tachycardia has sinus P waves, although these can be dif cult to identi y when the P wave uses with the T wave o the preceding QRS complex. This situation usually occurs in critically ill patients with heart rates greater than 180 bpm, patients receiving vasopressors, or when there has been signi cant volume loss. Besides sinus tachycardia, atrial tachycardia is the most common long R-P tachyarrhythmia. P waves in these instances will be

Figure 102 11 RP interval in the assessment of SVT. (From Michaud GF, Stevenson WG. Supraventricular tachyarrhythmias. In: Kasper DL, et al., eds. Harrison’s Principles of Internal Medicine, 19th ed. New York: McGraw-Hill; 2015, Fig. 276-2.) 735

Physical examination: The patient was alert, oriented, and able to respond appropriately to questioning. Remainder o exam was notable or a di cult to assess JVP, distant heart sounds, absence o murmur, and clear lungs. No bruits were appreciated.

TABLE 102-3 R-P Intervals

■ PRE- AND POSTARRHYTHMIA ECG ASSESSMENT What is the mode of onset or termination of the tachyarrhythmia? Telemetry monitoring, Holter monitors, and pacemaker or de brillator interrogation, i available, can provide use ul in ormation about the onset and termination o an abnormal rhythm. Premature atrial complexes (PAC) immediately prior to arrhythmia onset suggests paroxysmal SVT. Sudden onset or o set o SVT is typical or AVNRT, AVRT and atrial tachycardias, whereas sinus tachycardia and MAT typically have a gradual onset. In addition, response to vagal maneuvers or adenosine is indicative o AVnodal-dependent reentrant arrhythmias.

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Short RP tachycardia (RP interval ½ RR interval) - Sinus tachycardia - Atrial tachycardia - Atypical AVNRT - PJRT (permanent junctional reciprocating tachycardia) - Sinus node reentry tachycardia

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I the patient is stable, obtain a 12-lead ECG to look or any changes rom the baseline ECG that might suggest cardiac ischemia and or the presence o pre-existing bundle block. The clinician should examine or evidence o a prolonged QT interval, AV dissociation, capture and usion beats, extreme axis deviation, or atypical bundle branch block that might suggest pre-existing structural heart disease and increase the likelihood o ventricular arrhythmias. Although uncommon, ECG changes suggestive o Wol -ParkinsonWhite (WPW), precordial ST abnormalities characteristic o the Brugada syndrome, and epsilon waves seen in arrhythmogenic RV dysplasia all have important management implications. A baseline ECG may allow or comparison o the QRS complexes during the tachycardia with the con guration o isolated ectopic beats preceding the tachycardia. Pre-excitation apparent during normal sinus rhythm would indicate that the tachycardia is due to an accessory pathway. Isolated PACs may lead to atrial group beats, atrial tachycardia, AF or AFL. When the atrial tachyarrhythmias terminate, isolated PACs may ollow. Likewise, when the QRS con guration during isolated PVCs be ore and a ter the tachycardia is identical to that present during the tachyarrhythmia event, the rhythm is con rmed ventricular. O note, while requent premature beats or runs o nonsustained VT could suggest the presence o structural heart disease, isolated premature beats on prior ECG are o little prognostic value. Amongst patients without known heart disease, 24-hour Holter monitoring reveals PACs in 99% o patients, and PVCs in 80%.

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recovery room she was noted to be hypoxic as O2 sat declined to 70% while receiving 4 L o nasal oxygen while sleeping and was administered 100% NRB mask with improvement o her oxygenation level to ≥96%. Back at the bedside: The covering team rapidly assessed the patient’s airway, breathing and circulation, placed pads on the patient and brought a de brillator to the bedside. Her baseline ECG (Figure 102-12) was notable or sinus bradycardia, heart rate 54 bpm, normal intervals, normal axis, normal R wave progression, and no ST-T abnormalities. The baseline ECG was o cially read by a cardiologist as normal. History of present illness: No prior history o arrhythmia, coronary artery disease, or cardiomyopathy. She denied any chest pain, palpitations, shortness o breath, lightheadedness, dizziness, syncope, or diaphoresis. She had no history o substance abuse, including alcohol. On review o systems, her only complaints related to her recent hip surgery. Review o her home medications and her current medications were notable or her blood pressure medications (amlodipine, lisinopril, and hydrochlorothiazide), extended release bupropion, calcium, vitamin D, and omeprazole. New medications since hospitalization included enoxaparin, war arin, and morphine via a patient-controlled analgesia (PCA).

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Figure 102 12 Baseline ECG for Case 102-1. 736

CASE 102-1 (continued)

C H A P T E R 1 0 2 T a c h y c a r d

For hemodynamically stable patients, physicians should per orm a targeted history and physical examination speci cally looking or signs and symptoms o signi cant cardiopulmonary and vascular disease. The neck veins should be examined or the presence o cannon A-waves that match the rate o tachycardia due to atrial contraction during ventricular systole when the tricuspid valve is closed. Canon A-waves would not occur in sinus tachycardia, ectopic atrial tachycardia, or atrial utter. Their presence does not di erentiate the two principal types o AVreentrant tachycardia. Less commonly, cannon A-waves may occur in VT when retrograde AV conduction depolarizes the atria during ventricular systole. For the postoperative patient, electrolytes, cardiac enzymes, and complete blood count should be obtained in addition to a resting ECG. Special attention should be made to repletion o potassium and magnesium. Oxygen should be administered as necessary and continuous ECG monitoring should be provided.

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carotid massage is a reasonable but very imprecise way to determine whether cerebrovascular disease is present, but most experts would avoid carotid massage i they identi ed a cervical bruit. Adenosine potently and transiently blocks AV nodal conduction, and would be expected to terminate AV-nodal dependent rhythms such as AVNRT or AVRT. In the setting o AFL or atrial tachycardia, transient AV block by adenosine may decrease ventricular rate and uncover atrial activity that was previously hidden and acilitate rhythm recognition. For WCTs not known to be ventricular in etiology, i the patient is hemodynamically stable and the rhythm is regular and monomorphic in pattern, then adenosine is a reasonable treatment option. Expected treatment or diagnostic response would be similar as or SVTs previously listed. VT does not typically respond to adenosine, although some orms o idiopathic VT (most commonly right ventricular out ow tract VT) may terminate with adenosine therapy. Be ore administering adenosine, physicians should speci cally inquire about a history o asthma or reversible COPD and whether the patient is receiving dipyridamole. Adenosine can trigger acute bronchospasm in vulnerable patients and dipyridamole can potentiate AVblock. At the time o administration, they should also warn the patient about transient sensations o chest tightness, nausea, and ushing.

NEXT STEPS

POSTOPERATIVE TACHYCARDIA Evaluation: 12-lead ECG (Figure 102-13) was notable or a regular heart rate o 118, a wide complex QRS with LBBB morphology, le t axis deviation, and no visible P waves. There were no ST segment abnormalities, and T wave changes were appropriate in the setting o LBBB. Neither her baseline ECG nor this ECG demonstrated the hallmarks o WPW, and it did not meet Brugada criteria or the diagnosis o VT. Together with the absence o known structural heart disease, stable vital signs, and lack o ischemic symptoms, the clinician was most concerned or SVT with aberrant conduction.

CASE 102-1 (continued) POSTOPERATIVE TACHYCARDIA Management: Vagal maneuvers were attempted but had no ef ect on rhythm. Given the low suspicion or VT or pre-excitation, and ECG showing regular and monomorphic rhythm, adenosine was deemed appropriate or use. 6 mg Adenosine IV push was administered ollowed by rapid saline ush but had no ef ect. A 12 mg IV dose transiently decreased the heart rate without appreciable change in morphology. The clinician then administered 5 mg IV metoprolol or two doses, with resulting decrease in heart rate to less than 100 bpm, and P waves became clearly evident. A ter a ew minutes at the lower heart rate, the QRS complexes transitioned to narrow complex morphology (Figure 102-14). The patient remained stable without change in vital signs. Her repeat 12-lead ECG showed narrow QRS complexes, normal axis and intervals, and resolution o the previous LBBB morphology (Figure 102-15). Her laboratory tests including electrolytes and cardiac enzymes were unremarkable.

■ ATTEMPT TO SLOW OR TEMINATE THE TACHYCARDIA The treatment options or tachycardia depend on identi cation o the underlying mechanism. Acutely ill patients o ten have dif culty per orming the Valsalva maneuver, during which they maintain a orced expiratory e ort against a closed glottis. The examiner may give the patient simple instructions to insert his index nger in his or her mouth, close the mouth around his or her nger, and exhale into a closed space. Auscultation or carotid bruits prior to per orming

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Figure 102 13 Postoperative sinus tachycardia. 737

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Figure 102 14 Monitor tracing with slowing return to normal sinus rhythm with narrow complex QRS.

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Intravenous administration o AV nodal blockers may reduce the ventricular rate and alleviate distressing symptoms despite persistence o the rhythm disturbance. β-Blockers or nondihydropyridine calcium-channel blockers are pre erable to adenosine in patients with atrial tachycardias. Importantly, AVnodal blockers are contraindicated in patients with pre-excitation AF, since slowing the native pathway may precipitate conduction down the accessory pathway, paradoxically increasing the ventricular rate. In these patients, antiarrhythmic therapy such as procainamide may be necessary or management, and expert consultation is recommended. For surgical patients already taking a β-blocker, the negative inotropic e ects o calcium channel blockers may be accentuated. Calcium-channel blockers should not be used or rate control in the setting o severe heart ailure (New York Heart Association Class III/IV) due to risk o cardiac decompensation. β-Blockers or digoxin are appropriate alternatives based on clinical status.

CASE REVIEW—ASSESSMENT OF THE POSTOPERATIVE PATIENT WITH TACHYCARDIA In this patient, the tachyarrhythmia proved secondary to sinus tachycardia with a rate-dependent LBBB morphology. Tachycardiacontingent bundle branch block may occur i either the right or le t-sided bundle branch reaches its e ective re ractory period and cannot conduct impulses to match the rapid rate o the tachycardia. In a patient with paroxysmal SVT-related WCT and a structurally normal heart, the bundle branch pattern usually has a typical appearance, identical to conventional bundle branch morphology. Sinus tachycardia is a common nding in the postoperative period due to the adrenergic drive that develops as a result o hypotension, volume shi ts, acute blood loss, pain and/or anxiety. Further treatment o her tachycardia would ocus on recognition and treatment o these primary causes. During the patient’s workup and treatment, the presence o P waves eliminated the possibility o atrial brillation, and no utter waves were appreciated with slowing o the rhythm in response to vagal maneuvers. Pre-excitation or conduction over an accessory pathway may cause the QRS morphology to be wide during SVT, but without delta waves or shortened PR intervals on her baseline ECG, WPW with a reentrant circuit seemed unlikely. Other historical eatures to consider include the use o bupropion, which can cause tachycardia and arrhythmia.

PRACTICE POINT

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Calcium-channel blockers should not be used or rate control in the setting o severe heart ailure (New York Heart Association Class III/IV) due to risk o cardiac decompensation. β-Blockers or digoxin are appropriate alternatives based on clinical status.

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Figure 102 15 ECG prior to discharge with resolution of rate-related LBBBpattern. 738

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Link MS. Clinical practice. Evaluation and initial treatment o supraventricular tachycardia. N Engl J Med. 2012;367(15):1438-1448.

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Brugada P, Brugada J, Mont L, et al. A new approach to the di erential diagnosis o a regular tachycardia with a wide QRS complex. Circulation. 1991;83:1649-1659.

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Management o tachyarrhythmia is in uenced by hemodynamic status and presence o prior structural heart disease. For all patients, electrolytes, cardiac enzymes, and a complete blood count should be obtained in addition to a resting ECG. Oxygen should be administered as necessary and continuous ECG monitoring should be provided. Serum K+ and Mg 2+ should be repleted, hypoxia corrected, underlying precipitants such as ailure to administer home medications, pain and withdrawal states identi ed and treated.

SUGGESTED READINGS

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Is this patient hemodynamically stable? Are the QRS complexes narrow or wide? Is the rhythm more likely to be ventricular in origin? I the origin o the rhythm is likely supraventricular, what is the rate o the tachycardia based on the R-R interval? Is the rhythm regular? Are P waves present, and i so, is their morphology the same as the baseline ECG in normal sinus rhythm? What is the R-P interval?

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A stepwise approach to a hospitalized patient with a tachyarrhythmia should begin with asking the ollowing questions:

Clinicians should always anticipate the possibility o requiring emergent electrical cardioversion or de brillation in the management o acute tachyarrhythmias. Persistent tachycardias unresponsive to the usual measures or clinical deterioration should prompt emergent specialty consultation.

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Whinnett ZI, Sohaib SMA, Davies DW. Diagnosis and management o supraventricular tachycardia. BMJ. 2012;345:e7769.

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The Geriatric History and Physical Examination Arline D. Bohannon, MD Peter A. Boling, MD

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INTRODUCTION The US population o adults aged 65 years and older will double within the next 20 years. This aging population includes many adults who use hospital care extensively. In 2005, an estimated 35 million non ederal hospital discharges occurred in the United States excluding newborns, and while older adults (65+) comprise 12% o the population, they accounted or 35% o hospital stays and increasingly o ten enter through the emergency room. For example, or patients 80 years and older, 55% were admitted through the emergency room in 1997 compared with 64% in 2002. Risk o intensive care unit (ICU) admission and ICU utilization also rise with age, peaking in the very old: in those aged 85 years or more there were 58.2 admissions per 1000 individuals and 195.8 days per 1000 individuals, compared with 3.8 admissions per 1000 individuals and 11.5 days per 1000 individuals in those 18 to 44 years old. Individuals 85 years old and older were 3.75 times more likely to be admitted to the ICU than those aged 18 to 44 years a ter controlling or comorbid illness. Risk o ICU admission rates increased with admission to surgical unit, and presence o multiple comorbid illnesses especially cardiovascular and renal disease. Risk o death is increased among elderly patient nearly 25% o all hospital deaths occurred in patients over 85 years old. Normal aging reduces physiologic reserve and the ability to maintain homeostasis under physiologic stress even in the best o circumstances. Chronic disease, the stress o acute illness precipitating admission, and polypharmacy add to vulnerability in this heterogeneous population. Furthermore, the hospital experience disrupts normal li e rhythms in a oreign environment away rom amiliar cues. Hospital procedures and policies en orce dependency and immobility that is o ten related to physical restraints; expose the patient to multiple un amiliar people involved in direct patient care, urther exacerbated by unit trans ers. The hospital setting disrupts sleep and nutrition due to lighting, unit noise, and interruptions such as requent blood drawing, per ormance o vital signs and tests. Use o sedatives or medications with anticholinergic side e ects —sometimes unavoidable during general anesthesia — and inadequate pain management urther exacerbate the risk o hospital acquired complications, including delirium, depression, in ection, malnutrition, deconditioning, alls, and pressure ulcers. Adverse outcomes include death, a prolonged hospital stay, nursing home placement and increased long-term dependency. The incidence o delirium during hospitalization ranges rom 11% to 42% and unctional de cits related to delirium may persist long a ter hospital discharge. Even in patients admitted or cardiovascular disease rather than in ection or dehydration, delirium is associated with higher unexpected in-hospital death which is also an important quality measure. Studies have shown that 30% to 60% o older people develop new dependencies in activities o daily living (ADL) during their hospital stay. Pressure ulcers, considered a preventable complication o hospitalization, are also associated with increased length o stay and health care cost, to the point that they are being called “never” events or which Medicare will re use to pay. The median incidence o pressure ulcers in hospitalized elderly persons varies rom 5% to 16% and has not decreased in recent years. There is evidence that some pressure ulcers develop early during hospitalization, a ter only a ew hours o immobility-induced pressure, yet the evidence o the tissue injury may not appear until days later, and may worsen even a ter the pressure is relieved. One large study

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A geriatric history must include an assessment o the cognitive, unctional, psychological and social domains. In order to obtain a complete patient history, clinicians should communicate with amily members and caregivers or in ormation about baseline unctioning and with the primary care provider on the day o admission. Inpatient providers need this in ormation to de ne and then achieve goals o hospitalization, which include avoidance o complications that might exacerbate preexisting conditions that make the patient even more vulnerable to a prolonged hospital stay and need or permanent placement upon discharge. The team should encourage liberal visiting by amily and riends especially during meals and evening hours, in orm the amily o the risks o hospitalization, and engage them in preventative measures such as orienting the patient, explaining the hospital routine, and assisting with ambulation. The amily should bring in the patient’s hearing aid, glasses, and any assistive devices that will acilitate optimal unction. E ective communication during the patient interview always begins with speaking in the patient’s native language and at the level appropriate or the patient’s educational background and cognitive unction. The clinician should also take time to obtain a meaning ul history rom elderly patients by:

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Geriatric medicine ocuses on our unctional domains— physical, cognitive, psychological, and social—that may be used to assess quality o li e and goals o care. In addition to treating the cause or admission, a multi aceted approach may improve outcomes by identi ying disability, taking steps to improve unctional per ormance, instituting preventative measures to limit iatrogenic complications and disability, and by promoting wellness and independence. This chapter will describe the essential history and physical exam components that should be routinely per ormed or hospitalized elderly patients in addition to the complete admission history and physical examination ordinarily per ormed or younger patients and explain how to actor this in ormation into discharge planning.

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ound that 6% o patients developed one or more hospital-acquired pressure ulcers within 2 days o hospital admission. Risk actors or new pressure ulcers include increased age, male gender, A rican American ethnicity, immobility (requiring assistance with turning in bed), trans er rom nursing home, nutritional compromise, body mass index (BMI) less than 18.5, the presence o a pressure ulcer at admission, and urinary and ecal incontinence. There are two things or hospitalists to consider: checking or evidence o skin injury on admission, a task shared with nurses, and looking or ways to prevent skin injury during the hospital stay. (See Chapter 149 [Pressure Ulcers] and Chapter 165 [Principles o Geriatric Care] or a discussion o evidence-based comprehensive models o care to prevent inpatient complications.) Not only are the personal costs o acute illness and related complications high but also, in a rapidly growing older population, the impact on health care costs is also high. Examples include delirium and unctional decline during hospital stays. The occurrence o delirium more than doubles the impact on health care costs, and with care ul attention, some o this may be avoided. Annual estimated costs in the United States attributable to delirium range rom $38 to $152 billon due to increased mortality and morbidity, prolonged hospital stay, unctional decline and long-term institutional care. With 42% o the US national health care budget spent on inpatient care and readmissions accounting or one quarter o Medicare inpatient expenditures, reduction in readmissions is becoming a ocal point in health care policy and hospitals may lose reimbursement when preventable readmissions occur. The elderly patient admitted to the hospital should be considered a “high-risk senior,” de ned as those at risk or developing health-related crises, simply by virtue o being hospitalized. The rst hospitalization o an elderly patient, in particular, may o er a window o opportunity or identi ying those at risk or urther unctional disability and clari ying targets or timely intervention to prevent or delay urther decline and a cascade o readmissions. The hospitalist should provide an actionable assessment that will lead to an interpro essional, multidisciplinary patientcentered approach utilizing case management, therapies (OT and PT), appropriate consultation, disease management programs, and home care. Optimal practice involves targeting posthospital services and service design to be cost-e ective and e cient: the right care in the right place at the right time, based on need. The admission history and physical examination is a multistep process o acquiring partial data that will lead to a provisional diagnosis. Physicians are taught to seek a diagnosis that will explain all or most aspects o a patient’s signs and symptoms at presentation. However, elderly patients commonly have multiple major comorbid conditions o varying severity that may a ect the initial presentation o acute illness. Unlike younger patients, whose signs and symptoms usually re er to a diseased organ, ill elderly patients commonly present with nonspeci c signs and symptoms such as lethargy, con usion, alls, and incontinence and decreased ability to per orm ADLs. Painless myocardial in arction, pneumonia without cough, apathetic hyperthyroidism, and depression masquerading as dementia are examples o common yet atypical presentations. A change in mental status, gradual debilitation, and nonspeci c symptoms is also characteristic o tuberculosis in the elderly which is ortunately uncommon but treatable and should not be overlooked. This patient population has changes in T-cell immune unction leading to declining delayed hypersensitivity reactions so that only 5% to 10% o 90 year olds will have a positive PPD despite a 90% rate o prior TB exposure. In addition, in older patients there may not be one uni ying diagnosis to explain all new symptoms, some o which may be drug-related. There ore, clinicians need to maintain a high index o suspicion, incorporate risk actors into clinical decision making, care ully review all medications and treatments, obtain in ormation rom multiple sources, and per orm a comprehensive examination.

• Addressing the patient by his or her last name. • Trying to minimize extraneous noise and interruptions. • Sitting opposite the patient at eye level, smiling, and speaking •

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slowly with a low voice. Inquiring about hearing de cits, con rming that the patient can hear the conversation, and asking him or her to repeat back what has been said. Raising the volume o his or her voice, i necessary, but not shouting (as shouting may be misinterpreted as anger). Writing the questions down in a large print, i the patient does not have his hearing aid or still cannot hear. Always allowing plenty o time or the patient to respond to questions. Trying to reassure the patient that he or she is in a sa e environment. Engaging the patient to speak about his or her interests. Using visual aids in the room to identi y caregivers and being readily available when amily members visit.

■ THE COGNITIVE DOMAIN The prevalence o cognitive impairment doubles every 5 years a ter the age o 65. Forty to ty percent o 90 year olds will su er rom dementia. In the early stages o dementia, amily members and riends o ten notice behavioral changes but may deny the symptoms or neglect to mention the symptoms to busy medical practitioners. Many patients do not complain or volunteer any in ormation about memory loss unless speci cally questioned. The interviewer should try to determine i the patient has an underlying 741

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A 79-year-old emale with hypertensive heart disease, mild chronic obstructive lung disease, and dementia is admitted to the hospitalist service a ter calling an ambulance or chest pain. On admission the plan o care was discussed by e-mail with her primary care physician who agreed with ruling her out or a myocardial in arction and then discharging her to home i her cardiologist agreed. She had not been seen in one year due to missed appointments. The cardiologist noted that she had had a recent negative pharmacologic stress test and did not recommend any urther workup. The patient lives alone and denied any problems with ADLs or IDLs. Her son lived nearby but was unavailable. The team excluded a myocardial in arction and sent o some lab tests or causes o impaired cognition (thyroid unction, B12, RPR) in addition to the admission blood work. She was dressed and eager to leave the hospital. She had normal f uent speech, attention, was well groomed, and able to walk without assistance. Two days later, her attending hospitalist called her home to be sure that she would ollow-up with her primary care physician. The patient answered the telephone, and then put the receiver on a table. For the rest o the a ternoon the signal was busy. Concerned, the hospitalist discussed this with case management who contacted Elder Services. Apparently, this patient had not been unctioning well at home, and, in act, there had been multiple—too numerous to count—police visits to her apartment to check on her over the last year. This case highlights the importance o a third party interview when questioning patients with dementia.

On admission, clinicians should interview caregivers about baseline cognition and recent changes in mental status. Delirium is an acute decline in attention and cognitive unction characterized by waxing and waning mental status which likely started in the last ew days or weeks. Delirium is subacute by nature and should not be con used with dementia which has an insidious onset, chronically present or years by the time o diagnosis, and usually does not progress abruptly. Recent changes in alertness, con usion, agitation, disruption o daily routines (sleeping more or less than normal, eating poorly) are common signs o delirium. These symptoms are sometimes subtle but noticeable to the people who live with the older adult and may sometimes precipitate a “social admission” or “placement” which may not be necessary when the delirium resolves. In such scenarios, caregiver burnout should be assessed and early involvement o social work help is vital to explore the social support situation. Delirium itsel is most o ten seen in patients with existing dementia, but it can occur in patients with no prior cognitive de cits i the new stress is severe enough. The examiner should probe or evidence o cognitive impairment pre-existing be ore the acute illness while also inquiring about other risk actors or developing delirium-poor baseline unctional status, railty, polypharmacy, CNS-active medications, chemical dependency, and number o medical comorbidities— particularly cerebrovascular and cardiovascular diseases, chronic liver or kidney disease, and visual or hearing impairment. See Chapter 81 (Delirium) and Chapter 166 (Agitation in Older Adults). Each provider should spend extra time making sure that the “home medication list” is correct while obtaining the medical history. There is evidence that errors are requently made on the admission medication list which leads to a high likelihood or errors 742

at the time o discharge. Someone on the inpatient team should veri y home meds with patient, amily and outpatient pharmacy, and question medications or doses that seem unusual or potentially ill-advised in an older patient. Hospital admission is a good time to re-evaluate the patient’s regimen, working in concert with outpatient providers, who know the patient well.

■ THE PHYSICAL DOMAIN OF FUNCTION The geriatric physical domain includes unction, nutrition, vision, and hearing. Functional status should be assessed by determining the elder’s ability to per orm basic and instrumental ADL. Basic ADLs, essential to independent living, include seven items in a standardized, widely accepted scale: bathing, dressing, eating, toileting, trans erring, ambulating, and maintaining continence. Bathing is the basic ADL with the highest prevalence o disability and o ten the reason why home health aids provide care o the elderly. As the patient perceives di culty with bathing, he or she may change the task to sponge baths or neglect altogether. In patients without impaired cognition, sel -report o daily unction is reliable; in those with impaired cognition a third party interview should con rm this in ormation. Mobility may be assessed by asking i the patient has di culty walking outside, rom room to room, or climbing a f ight o stairs. Presence o new ADL de cits commonly acquired during hospitalization predicts both mortality and institutionalization. Commonly the acute admitting illness is the result o progressive deteriorating chronic health status at home, which chronic conditions become apparent during the hospital stay, when underlying problems emerge such as malignancies, vascular disorders, and complications o longstanding metabolic illnesses like diabetes. The prevalence o sarcopenia which contributes to railty in elderly hospitalized patients is high, reported in one study at around 22%1; this is another reason why unctional assessment is particularly important when preparing or the consequences o immobility and catabolic states o ten seen during hospital care episodes and preparing patients or discharge. Memory loss, medical illness, depression, inability to shop, and nancial issues may impact nutritional status. Dys unction and diseases o the oral cavity may a ect overall health, social interactions, and increase the risk o malnutrition. Poor oral hygiene may be compromised due to alterations in vision, manual dexterity, upper extremity unction, or alterations in salivary f ow. The examiner should speci cally inquire whether the patient has regular dental visits that may uncover untreated dental disease which is less likely to produce symptoms compared to younger patients. Dysphagia or the inability to initiate a swallow or the sensation that solids or liquids or both do not pass easily rom the mouth to the stomach, odynophagia, and severe vascular disease that a ects the celiac axis may cause ear o eating and result in malnutrition. Weakness o the so t palate or pharyngeal constrictor muscles can cause dysarthria and nasal regurgitation o ood. In addition to direct observation o nutritional status, the interviewer should inquire about meals, whether the patient prepares them or has assistance, and whether the patient has changed the way he or she per orms the IADLS such as using the telephone, shopping and cooking meals, managing nances, doing housework and laundry, and managing transportation. A weight loss o 10 pounds in the preceding 6 months or 5% in the past month indicates increased risk or malnutrition and predicts unctional limitations. In this context, the examiner should consider all medications including over the counter medications such as antihistamines which can exacerbate cognitive impairment and may a ect appetite and discover whether the

Martinez BP, Menezes Santos Batista AK, Gomes IB, Olivieri FM, Camelier F, Camelie AA. Frequency o sarcopenia and associated actors among hospitalized elderly patients. BMC Musculoskelet Disord. 2015;16:108.

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■ SOCIAL HISTORY DOMAIN In addition to li estyle habits such as tobacco and alcohol use that are commonly asked about, social history in geriatric patients should explore current living situation and any economic issues that interere with patient wellbeing; plus support systems or daily activities that include meal preparation, mobility, bathing, dressing and toileting, transportation, and medication administration. In addition, the clinician should recognize symptoms that may suggest elder mistreatment or neglect. See Chapter 167 (Elder Mistreatment). The physician may then combine an awareness o unctional limitations that is gained during the medical history with knowledge o social supports to enhance the posthospital care plan. The patient’s caregiver support rather than the patient’s primary diagnoses or unctional disability o ten determines whether the patient can be discharged to his or her home. O ten this in ormation is best obtained rom amily and usual caregivers. The admission assessment should identi y patient’s primary support, health care proxy, and any potential barriers or return to the community. GERIATRIC PHYSICAL EXAMINATION The examiner should search or and document pre-existing conditions at the time o admission that predispose elderly patients to complications acquired during hospitalization such as malnutrition

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The rst step is to review vital signs not only in the context o the complaint precipitating admission but also to assess prognosis and unction. The pulse pressure (PP) and the systolic blood pressure (SBP) typically increase with age whereas the diastolic blood pressure (DBP) declines. According to Framingham data, age-related changes in blood pressure gradually shi ts rom the DBP as the strongest predictor o coronary artery disease in people less than 50 years o age to DBP, SBP, PP as approximately equal predictors in people aged 50 to 59 years, and SBP and PP as the strongest predictors in people over the age o 60 years. According to the Multiple Risk Factor Intervention Trial, isolated systolic hypertension (SBP > 140 mm Hg and DBP < 90 mm Hg) triples the risk o coronary heart disease and all-cause mortality in men over the age o 50. A higher PP >60 mg is an additional independent risk actor or myocardial in arction, carotid artery stenosis, end stage renal disease, renovascular hypertension, le t ventricular hypertrophy, cardiovascular events, and mortality. A wide PP greater than 50% o the SBP is also seen in aortic regurgitation and may be a clue to high f ow states such as hyperthyroidism, ever, symptomatic anemia, Paget’s disease, or rarely severe ex oliative dermatitis. A narrow pulse pressure PP less than 25% o the SBP coupled with cool extremities, altered mentation, Cheyne-Stokes respiration, and a resting tachycardia may portend severe ventricular dys unction and impending cardiogenic shock. (Re er to Chapter 93 [Hypotension].) A narrow pulse pressure may also be seen in aortic stenosis, pericardial tamponade, constrictive pericarditis, and tachycardia. Particularly i the patient or amily have reported dizziness, syncope, or alling, the blood pressure and pulse should be recorded while the patient is supine and again a ter standing or 1 to 2 minutes to detect orthostatic changes. Postural hypotension is de ned as a drop in mean blood pressure (MBP), namely, one-third SBP and twothirds DBP, o 20% or more. Alterations o the conduction system by disease or medications such as β-blockers may prevent a change in pulse. Orthostatic or postural hypotension is common in older patients both on admission and later during the course o hospital care. This nding has been reported in 30% o hospital stays, is easily overlooked in a busy Emergency Department where patients are on stretchers, and also on the wards since vital signs are usually taken while the patient is in bed, and orthostasis may later contribute to alls, in the hospital or a ter discharge. Too o ten, hospitalized patients are only assessed when lying in bed. The examiner should personally observe the patient’s breathing and respiratory rate which is too o ten recorded incorrectly on the vital sign sheet. I tachypnea is noted at rest, the patient may have unctional limitations due to respiratory insu ciency with hypoxia during exercise that may not be apparent at rest, or may have incipient heart ailure rom f uid administration during the acute illness or perioperatively, and increased work o breathing may be the only clue. An elderly patient with increased intracranial pressure ollowing stroke or a patient with severe heart ailure may have CheyneStokes breathing. Kussmaul’s breathing suggests metabolic acidosis. Biot’s breathing with irregular periods o apnea o ten seen in the setting o multiple strokes carries a poor prognosis. During quiet breathing an examiner can check or pulsus paradoxus, an exaggeration o the normal decrease in SBP with inspiration. Normally during inspiration the SBP may drop 0 to 10 mm Hg. Many conditions may cause a pulsus paradoxus such as constrictive pericarditis,

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Symptoms o depression have an adverse impact on quality o li e, risk o physical disability, slower recovery rom an acute illness, and a signi cant increase in the cost o medical services, even a ter adjusting or the severity o chronic diseases. Depression may be con used with dementia and may be chronic. However, orientation should be intact. The patient may be apathetic, express hopelessness, and make little e ort to per orm a task. For example, in the hospital a patient may re use to work with physical therapy whereas demented patients with impaired cognition in multiple domains usually make an e ort to per orm an assigned task. Clinicians should ask the patient whether he or she o ten eels sad, more irritable or depressed, treat underlying depression, and address anxiety and worries that inevitably develop during hospitalization. Some patients may require help with the bereavement process i they have lost riends or amily, as well as with loss o independence which can be equally damaging psychologically.

■ VITAL SIGNS

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and take steps to avoid urther deterioration. The baseline neurologic examination should assess cognitive unction (documenting the presence o delirium and depression), unctional status (including evidence o deconditioning and the presence o pressure ulcers), and hearing and vision.

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patient independently takes his or her medications. Anticholinergics, antihistamines, and certain antihypertensives can exacerbate poor dental hygiene by decreasing salivary f ow. See Chapter 9 (Principles o Evidence-Based Prescribing) and Chapter 73 (Patient Sa ety and Quality Improvement). Vision and hearing impairment increases the risk o alling and may be associated with depression, social isolation, and urther decline. For hospitalized patients, vision and hearing impairment, re erred to as sensory deprivation, not only inter eres with communication but also increases the risk or delirium and hence morbidity. Visually impaired patients may not be aware o their de cits and may have no idea o who is examining them. There are many reasons or visual impairment, but the physician should inquire whether the patient is still driving, has di culty seeing the television, reading or identi ying people in the room. I a patient is visually impaired, there should be a sign in the room so that people identi y themselves upon entering. Many elderly patients are also unaware o their hearing de cit due to the slowly progressive nature o usually symmetric sensorineural loss or deny it due to the stigma o wearing a hearing aid. Family members should be asked whether the patient hears them or plays the radio or television too loud. Clinicians may misinterpret hearing loss or cognitive impairment.

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tamponade, pulmonary embolism, right ventricular ailure, and asthma, and its presence is correlated with severity o illness. The patient should be weighed on admission and periodically during the hospitalization. A measure o body size and indirect measure o body at, a BMI o 18.5 kg/m 3 or less is a practical measure o underweight.

■ OBSERVATION

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Nothing tells the story like rsthand observation. I the patient is asleep, observe breathing be ore waking the patient up. Does the patient open his or her eyes when you enter the room? Does the patient all asleep during your conversation? Does the patient appear well nourished? Are they eating during your visit? Does the patient have tethers that can be removed such as oxygen, Foley catheters, intravenous lines or other monitoring devices? Is the patient wearing a diaper? Can the patient sit up without assistance during the examination? The examiner should re rain rom assisting the patient until the determination is made that the patient cannot do this on his or her own. I the patient can sit up without assistance, can the patient walk without risk o alling? Simply watching the hospitalized patient get out o bed and take a ew steps or use the telephone provides valuable insight into the patient’s ability to per orm ADLs. There are ormally validated measures such as timed walk or timed “Get Up and Go” which provide numeric data: 20 seconds on the Up and Go de nes high risk o institutional care. (See Chapter 87 [Falls].) A physician who does not attempt to get the patient out o bed or pay attention to their ability to participate in sel care will o ten miss the mark when it comes to making proactive plans or continuing care, resulting in last minute scrambling or alternative options and dissatis action.

■ PRESSURE ULCERS AND THE SKIN EXAM There are both medical-legal and regulatory reasons or a thorough, documented skin assessment upon admission and at regular intervals during hospitalization, with special attention to high-risk areas. Much o this work can and should be done by nurses, but the physician should lead this initiative, “con rm nurses ndings” when problems are ound, and per orm independent assessments based on clinical judgment and patient risk actors. In addition to the sacrum, ischial areas, and trochanters, physicians should pay attention to the heels, an area o ten overlooked, and be alert to erythema o intact skin in high pressure areas that does not resolve when pressure is removed (thus consistent with a Stage 1 pressure ulcer). Physicians should recognize immobility as a major risk actor or skin damage and when making rounds, ask the nurses about the skin, and examine the skin o immobilized patients. (See Chapter 72 [Pressure Ulcers].) Reducing the incidence o pressure ulcers requires a multidisciplinary team approach, identi ying patients at risk and intervening early. Preventive strategies shown to be e ective include risk assessment on admission and 48 hours later. Pressure ulcers observed early in the hospital stay may all into two major groups: (i) super cial ulcers induced by riction or transient pressure and that are usually quickly resolved and (ii) deep ulcers ref ecting a sustained, pressure-related ischemic injury to deep layers o the skin and subcutaneous tissues, occurring days earlier, sometimes be ore hospitalization, but delayed in clinical presentation and appearing days later. These wounds may take months to heal.

■ COGNITIVE DOMAIN Although busy inpatient physicians cannot be expected to do an indepth mental status examination on every patient, the usual “alert and oriented” questions are inadequate to detect clinically signi cant cases o dementia and delirium. A more complete assessment 744

is needed or every older inpatient. Memory loss is typically the rst sign o dementia. The diagnosis o “dementia” is too o ten added to the patient’s record when the real diagnosis is delirium or depression, or simply because the patient has been prescribed medications to enhance memory by another physician. I the patient cannot pay attention due to delirium, then screening or dementia will not reveal valid results. Dementia should be considered only when there is a history o chronic cognitive impairment dating back several months and su ciently severe to a ect social unctioning. Several brie screening tools or delirium are available and should be amiliar to inpatient care providers. The con usion assessment method (CAM) is the most studied. A positive CAM score requires evidence o an acute onset and f uctuating course plus a de cit in attention (the hallmark eatures), and at least one o two other eatures, which are disorganized thinking and change in level o alertness. The CAM-ICU version helps when patients cannot communicate verbally. The Delirium Rating Scale can be used to rate symptom severity. Validated measures to screen or dementia in nondelirious patients are available, such as the Mini Mental State Exam (MMSE); these require 3 to 5 minutes and some components may be physically di cult or acutely ill patients to complete. One strategy is to use the most reliable single component within the MMSE as an initial screen. That component is three-item recall (learning a list o three words and repeating them a ter brie distraction) which is the most speci c test o short-term memory, the common ground or all types o dementia. Three-item recall is a use ul clue but is not su cient by itsel . Combining recall with clock drawing is the Mini-Cog and in testing or dementia, the Mini-Cog has comparable sensitivity and speci city to the ull MMSE. Clock drawing may also be di cult in the inpatient setting. Nonetheless, whatever strategy is used by the hospital physician, it should go beyond simple orientation to person place and time. Baseline mental status testing should be a routine eature o all inpatient geriatric physical exams. And, when present, impaired cognition ound in the hospital should be placed in context with the history.

■ DISCHARGE PLANNING Despite recent advances in electronic records, patient pathways, and technology-assisted decision support, the ollowing actors identi ed nearly 20 years ago still cause delayed discharge rom hospital: inadequate assessment o the patient by health care pro essionals resulting in poor knowledge o the patient’s social circumstances; and poor organization, or example, late booking o transport preventing timely discharge rom hospital and poor communication between the hospital and providers o clinical services in the community a ter discharge. Discharge planning should begin at the time o admission. When preparing or discharge, incorporating a solid understanding o the geriatric patient’s unctional status, clinical condition and social support needs and ensuring adequate provision o continuing care ollowing discharge may reduce the likelihood o return to hospital with preventable problems such as alls. Discharge planning begun at the time o admission can have impressive results. One classic 1995 study ound 50% ewer readmissions a ter applying ocused care processes designed or selected older patients with recurrent admissions or heart ailure related to uncontrolled hypertension or ischemia. Geriatric cardiologist medication review, intensive patient education, and speci c home nursing ollow-up were the main interventions. The literature on discharge planning is extensive and o ers both success stories and ailures. The most success ul studies select and concentrate on patients who are inherently vulnerable to poor transitions rom hospital to home, and provide a ocused, robust

C H A P T E R 1 0 3 T h e

e ective. In-person intervention (rather than telephonic care management) is ound in the most success ul models, and the experience and expertise o discharge planners also makes a di erence. O note, there are varied control group costs in the ormal studies o transitional care interventions, and combined with the di erences in magnitude o impact, one must conclude that each institution should consider targeted populations, usual care settings, and local resources when designing strategies. The Society o Hospital Medicine has identi ed transitions o care as a major quality issue and initiated BOOST (Better Outcomes or Older adults through Sa er Transitions) to improve transitions o care or the elderly in Pennsylvania and more recently in Michigan (Table 103-1).

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intervention. Between 2002 and 2006, comparing historical costs and postintervention costs incurred at our medical center, we saw a sharp reduction in readmissions and days in the hospital or selected patients when a Naylor model transitional care model helped complex patients posthospital and the same pattern continued through 2015. Many discharge planning programs have reported increased quality o li e and patient satis action. Neither optimal care nor health care utilization bene ts occur when team members work in isolation. Multidisciplinary intervention: a combination that includes discharge planning, geriatric assessment with unctional and cognitive evaluation, and medication review- is ar more likely to be

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Project BOOST Facts GOAL: The goal o Project BOOST (Better Outcomes or Older adults through Sa e Transitions) is to improve the care o patients as they transition rom the hospital to home.

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TABLE 103-1 BOOST (Society of Hospital Medicine)

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APPROACH: 1. Create a national consensus for best practices. Project BOOST’s advisory board includes representatives rom the Agency or Healthcare Research and Quality (AHRQ), The Joint Commission, Centers or Medicare and Medicaid Services, Blue Cross and Blue Shield Association, pharmacy, nursing, geriatricians, patient advocates, and others. 2. Create resources to implement best practices. Project BOOST created a resource room-BOOSTing Care Transitions Resource Room, or quality improvement teams including: • Clinical toolkit (discharge planning tools, risk strati ication tools). • Data collection tools. • Project Management Tools (guidance or gaining institutional support, creating and managing a team). • Educational tools background in ormation or pro essionals new to quality improvement. • Review o key literature. • Exchange In ormation and Share Success stories. 3. Provide technical support. Project BOOST o ers several technical support options via the Project BOOST Mentoring Program. Participating sites will receive: • Day long training sessions ( ee-based). • Year-long coaching/mentoring program ( ree, courtesy o grant rom the John A. Hart ord Foundation).

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OUTCOMES: By improving discharge processes, Project BOOST aims to: • Reduce 30 d readmission rates or general medicine patients (with particular ocus on older adults). • Improve acility patient satis action scores. • Improve the institution’s H-CAHPS scores related to discharge. • Improve low o in ormation between hospital and outpatient physicians. • Ensure high-risk patients are identi ied and speci ic interventions are o ered to mitigate their risk. • Improve patient and amily education practices to encourage use o the teach-back process around risk speci ic issues.

PARTICIPATING SITES Any site can access the BOOST tool kit via the resource room ree o charge at www.hospitalmedicine.org/BOOST. Over 265 sites have downloaded the complete Implementation Guide which serves as a portable version o the resource room and will walk you through the steps improve the discharge process. There are two cohorts participating in the Project BOOST Mentoring Program. Cohort one, listed below started in September 2008. Six hospitals were selected to participate in Project BOOST’s pilot mentoring program: • Piedmont Hospital, Atlanta, Georgia. • Queens Medical Center, Honolulu, Hawaii. • University o New Mexico Health Science Center School o Medicine, Albuquerque, NM. • Hospital o the University o Pennsylvania, Philadelphia, PA. • Southwestern Vermont Medical Center, Bennington, VT. • ThedaCare: Appleton Medical Center, Appleton, WI; ThedaClark Medical Center, Neenah, WI.

(Continued)

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TABLE 103-1 BOOST (Society of Hospital Medicine) (Continued)

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Cohort two, listed below started in March 2009. Twenty- our hospitals were selected to participate in Project BOOST’s mentoring program:

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• Banner Good Samaritan Medical Center, Phoenix, AZ.

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• Kaiser Permanente Hospital West Los Angeles, Los Angeles, CA. • Cali ornia Paci ic Medical Center, San Francisco, CA. • University o Cali ornia, San Francisco, San Francisco, CA.

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• Greenwich Hospital, Greenwich, CT.

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• Morton Plant Hospital, Clearwater, FL.

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• Emory Craw ord Long Hospital, Atlanta, GA.

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• Emory University Hospital, Atlanta, GA.

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• Rush University Medical Center, Chicago, IL.

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• University o Kansas Hospital, Kansas City, KS.

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• UMass Memorial Medical Center, Worcester, MA.

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• University o Michigan, Ann Arbor, MI.

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• SSM St. Mary’s Health Center, St. Louis, MO.

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• Billings Clinic, Billings, MT.

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• Mission Hospital, Asheville, NC.

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• Lakes Region General Hospital, Laconia, NH.

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• Cooper Health, Camden, NJ.

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• Huntington Hospital, Huntington, NY.

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• Albert Einstein Healthcare Network, Philadelphia, PA. • Medical University o South Carolina, Charleston, SC. • San ord USD Medical Center, Sioux Falls, SD. • Baptist Hospital, Nashville, TN. • Chesapeake Hospitalists, P.C., Chesapeake, VA. • Aurora Medical Center, Summit, Milwaukee, WI.

■ AREAS FOR FUTURE RESEARCH Care o the hospitalized elder is challenging and requires an interpro essional, multidisciplinary approach to prevent and manage complications like delirium and decline in unctional status. Geriatric ocused history and physical exams are required to identi y patient at increased risk. One method to improve documentation o risk actors is use o templates consultation notes or inpatient notes adapted to an electronic medical records. Templates provide cues to document physical unction, mental status, social supports, advance directives and complete skin assessments. The electronic medical record can then trigger use o care sets or treatment protocols which restrict use o medications known to precipitate delirium, encourage early mobilization, and promote pressure relie . There remains a paucity o high quality published research on preventing complications in hospitalized elders, examining mortality, quality o li e, caregiver issues, health care utilization and cost. As the aging population is growing exponentially, it is imperative that interventions are developed, tested and proven to be reproducible in order to systematically improve the care o hospitalized elders nationwide.

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CONCLUSION Limited physiologic reserves, high comorbidity and complex social issues make the needs o elderly inpatients relatively unique among adults. Circumstances vary across settings and studies, including such issues as nancial assets, extent o managed care penetration in communities, availability o community assets, and strength o the local primary care work orce. Solid evidence shows that improved care processes including team-based assessments and rounds can materially reduce the incidence and consequences o delirium, pressure ulcers, and decrease length o stay, institutional care, hospital readmission, and avoidable health care costs. We have described the importance o the geriatric ocused history and physical that can provide value in ormation to target interventions to improve outcomes. Beyond what is known there is much research work yet to be done in urther re ning our clinical care o older patients. In particular, the roles o nonphysicians on the care team are an opportunity or sharing the work o structured and ocused yet comprehensive assessment. In the near uture, Medicare will require the team to document certain items, such as unction and cognition, in all hospitalized patients.

104

CHAP TER

The Neurologic Examination David J. Likosky, MD, SFHM, FAHA, FACP S. Andrew Josephson, MD

Key Clinical Questions 1

What elements o the history and examination are most use ul in lesion localization?

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What elements o the neurologic examination can be assessed at the bedside without ormal testing?

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What tests can be per ormed on the unresponsive patient?

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What scales and tools are used to document the indings o the neurologic exam?

INTRODUCTION The neurologic examination is central to the evaluation o patients with neurologic complaints. It relies heavily on the history and on hypothesis-driven physical testing. The neurologic examination can provide a great deal o in ormation quickly. Even when it is not diagnostic, it guides the appropriate choice o imaging and ancillary testing. However, i it is per ormed in a cursory ashion, one can easily miss clues to a diagnosis that may not be apparent on imaging. This chapter reviews the essential elements o the neurologic examination in evaluating patients in the hospital. IMPORTANCE OF THE HISTORY The history allows the hospitalist to narrow the range o diagnostic testing and per orm a more ocused and higher yield neurologic examination.

CASE 104-1 A 57-year-old right-handed man presents with an episode o syncope while typing a manuscript. He recalls no prior episodes but does have a history o well-controlled hypertension and hyperlipidemia. You are called by the emergency department physician to admit the patient to telemetry and rule out an arrhythmia. The patient recalls similar episodes that he has had or as long as he can remember. They were bothersome during school but are brie and in requent now. He also notes that they were worse when he was tired. When taking the neurologic history, the hospitalist should ocus rst on localizing the lesion, and then on developing a di erential diagnosis. Missed diagnoses are common in neurology when one jumps to a conclusion be ore establishing where the problem lies. Tempo is help ul. Does the process wax and wane, as in delirium? Is it steadily progressive, as in dementia? Or does decline occur in a stepwise ashion, as with multiple strokes? In patients with muscle weakness, pay attention to the pattern o weakness. Di culty rising rom a chair, carrying heavy loads, or brushing or washing hair suggests proximal weakness. Problems with opening a jar, opening a car door, or turning a key in a lock suggest distal weakness. In patients with sensory symptoms, is there loss o sensation (negative phenomena), such as the numbness resulting rom stroke, or inappropriate sensation (positive phenomena), such as tingling rom nerve root compression?

CASE 104-1 (continued) The patient’s physical examination was unrevealing. A computed tomography (CT) scan o his brain was negative, but an electroencephalogram (EEG) showed occasional epilepti orm discharges rom the le t hemisphere. The patient was begun on anticonvulsants at a very low dose and has had no urther episodes.

Without a detailed history, this patient might have been admitted to telemetry and had extensive and inappropriate cardiac investigations. He might have been discharged with the diagnosis o unexplained syncope and gone on to have a seizure at an inopportune 747

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time. With a care ul history, he leaves instead with a correct diagnosis and li e-altering therapy.

A undamental distinction in neurologic disease is deciding whether a central or peripheral lesion is responsible. Central lesions a ect the brain and spinal cord, and peripheral lesions a ect the anterior horn cells, peripheral nerves, neuromuscular junctions, or muscles. Localizing a lesion to the central or peripheral nervous system avoids excessive, shotgun imaging, in which may lead to inf ated costs and overdiagnosis. In the case above, there are elements that are likely central (a erent pupillary de ect, hyperactive ref exes, increased tone, and Babinski sign) and others that could be either ( oot drop). It would be help ul to urther de ne the abnormal sensation using dermatome and peripheral nerve maps (Figures 104-1 and 104-2). I the new abnormality does not con orm to the distribution o a peripheral nerve or dermatome, a central lesion is probable, and neuroimaging is indicated. Ordering an electromyogram (EMG) in this setting would be inappropriate and o low yield. In this case, the patient has lesions that are separated in space (di erent locations in the CNS) and time (old oot drop, new altered sensations). Magnetic resonance imaging (MRI) o the brain is ordered, which demonstrates multi ocal T2 hyperintensities that particularly involve the periventricular white matter, consistent with demyelinating lesions o multiple sclerosis.

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LOCALIZING THE LESION

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A major goal in neurology is to localize the lesion causing the patient’s symptoms. Diagnosis in neurology, as in other domains o medicine, relies partly on pattern recognition. Important patterns include the hemiparesis and language de cit o a dominant middle cerebral artery stroke, the cranial nerve ndings and crossed body involvement o a brainstem stroke, the distal neuropathy o diabetes, the ascending weakness o Guillain-Barré syndrome, and the diurnal variation o ptosis and diplopia in myasthenia gravis. However, many signs and symptoms in neurology are nonspeci c, and may be produced by lesions in more than one anatomical site.

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■ CENTRAL VERSUS PERIPHERAL

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CASE 104-2

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A 27-year-old man who has previously been healthy complains o strange sensations. You note that his mental status is normal, as are his cranial nerves, with the exception o an a erent papillary de ect on the right. He has ull strength, with increased muscle tone di usely, and developed a mild right-sided oot drop about a year ago, or which he never sought treatment. Sensation is normal except or much o his le t hemithorax. Re exes are mildly hyperactive, and a Babinski sign is present.

■ UPPER VERSUS LOWER MOTOR NEURON LESION When patients have weakness, it is help ul to localize the lesion to either the upper or lower motor neuron (Figure 104-3). Severity o weakness does not distinguish between these anatomical sites, but examination o tone, ref exes, and other elements o the exam

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Figure 104 1 Dermatome map. (Reproduced, with permission, rom Cunningham FG, Leveno KJ, Bloom SL, et al. Williams Obstetrics, 23rd ed. New York, NY: McGraw-Hill; 2010, Figure 19-3.) 748

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Me d. & la t. pla nta r n’s . (from p os ttib ia l n.)

S upe rficia l pe rone a l n. (from c ommon p e rone a l n.) S ura l n. (from tib ia l n.)

La t. cut. n. of ca lf (from c ommon fe mora l n.)

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Pos t cut. n. of thigh Me d. cut. n. of thigh (from fe mora l n. )

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S upe rficia l pe rone a l n. (from c ommon p e rone a l n.) De e p pe rone a l n. (from c ommon p e rone a l n.)

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C5 S upra clavicula r n’s. C6 T1 T2 Pos t. cut. 3 Me d.cut. n. of a rm ra mi 4 & inte rcos tobra chia l n. of La t. 5 thor. cut. 6 ra mi 7 n’s. 8 Pos t.cut. n. of fore a rm 9 (from ra d ia l n.) L1 10 11 La t. cut. n. of fore a rm Me d. 12 (from mus c uloc ut n.) cut. n. S1 Pos t. ra mi of of Ra dia l n. lumba r s a cra l fore a rm & coccyge a l n’s. Ulna r n.

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S a phe nous n. Ca lca ne a n bra nche s of tibia l & s ura l n’s

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Figure 104 2 Map of peripheral sensory nerves. Front (A). Back (B). (Reproduced, with permission, rom Haymaker W, Woodhall B. Peripheral Nerve Injuries, 2nd ed. Philadelphia, PA: Saunders; 1953.)

do (Table 104-1). When upper motor neuron weakness is present, the lesion must be in the brain or spinal cord. Lower motor neuron weakness may have multiple localizations (Table 104-2), none o which can be discerned through imaging studies o the brain and spinal cord; next steps may include EMG and nerve conduction studies (NCSs).

■ POSTERIOR FOSSA LESIONS

CASE 104-3 A 76-year-old woman is reportedly ound “twitching” in the hallway o her apartment building, a ter having been seen to be well 1 hour prior. She is intubated or airway protection. In the emergency department, she has a recorded blood pressure o 240/130 mm Hg. On exam, her right eye is abducted in downgaze, and the right pupil is larger than the le t. Cranial nerves are otherwise intact. She withdraws to pain ul stimulus with the right arm, which appears ataxic with movement. She is able to communicate intact sensation. She is hypore exic, and Babinski signs are present bilaterally. The posterior ossa contains the brainstem and cerebellum. Due to their bony encasement, even minor swelling may obstruct the outf ow o cerebrospinal f uid, leading to major morbidity and mortality. Brainstem signs include abnormal cranial nerve ndings, such as unequal or misshapen pupils and acial asymmetry. In addition, crossed signs—contralateral ndings in ace and body—may

be present. Many o these are present in this case. Our patient had urgent neuroimaging that did not reveal a hemorrhage and recovered ollowing thrombolysis or ischemic stroke. ESSENTIAL ELEMENTS OF THE NEUROLOGIC EXAMINATION An in-depth neurologic examination can take an exorbitant amount o time when not driven by a hypothesis. Many o the patients cared or by hospitalists warrant only a brie screening examination. It is particularly important to assess or underlying mental railty due to underlying dementia, as neurologic illness o ten becomes more apparent due to the stresses o hospitalization. This may take the orm o delirium unmasking dementia, or respiratory ailure revealing underlying neuromuscular weakness. Fortunately, much o the neurologic examination is observational. The attentive clinician may be able to document many essential elements o the exam without ormal testing: Mental status • Established during history taking when asking speci c

questions • Language f uency is apparent during the history Cranial nerves • Vision, eye movements, and sternocleidomastoid, as the

patient watches the examiner walk between the sides o the bed • Facial symmetry, lid strength, hearing, and tongue strength as the history is taken 749

Motor examination

Motor cortex

• Gross abnormalities can be seen as the patient moves in bed or

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Coordination

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very revealing • Observe the patient manipulating the nurse call button and moving the bedside tray, or ask the patient to retrieve a medication list rom a purse or drawer Sensory examination and ref exes • Usually require ormal testing or assessment

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The ability to test higher cognitive unctions such as memory and language is limited in patients who cannot sustain attention. Inattentiveness, or the inability to concentrate, o ten indicates delirium, particularly when accompanied by f uctuating mental status, alteration o consciousness, and disorganized thinking. Bedside tests use ul in assessing attention and delirium include: • Assessing the level o arousal (awake, drowsy, lethargic, or comatose); speak to nurses and amily members to assess whether mental status is waxing and waning; • Assessing the level o awareness (orientation to person, place, and time). Note that an oriented patient may still be con used, and a disoriented one may have psychosis, amnesia, or aphasia instead o delirium; • Days o the week or months o the year, orward and backward (serial 7s and spelling words backward are not good tests, particularly or patients who are illiterate or uneducated).

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Ante rior horn ce ll Pe riphe ra l ne rve Motor e nd-pla te

Figure 104 3 Anatomical localization of upper and lower motor neuron lesions. (Reproduced, with permission, rom Waxman SG. Clinical Neuroanatomy, 26th ed. New York, NY: McGraw-Hill; 2010, Figure 5-22.)

TABLE 104-1 Upper Versus Lower Motor Neuron Weakness

Pattern o weakness Function/ dexterity

Tone Tendon re lex Other signs

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Upper Motor Neuron Pyramidal

Lower Motor Neuron Variable

Rapid alternating movements slow and clumsy (indicates disease in cerebellar or corticospinal tracts) Increased Increased

Impairment o unction is mostly due to weakness

Babinski sign, other central signs (eg, aphasia, visual ield cut)

Decreased Decreased, absent, or normal Atrophy (except with problems o the neuromuscular junction)

Have the patient play a game that requires attention. For example, i the examiner taps once, the patient taps twice on the table; i the examiner taps twice, the patient does not tap on the table. Alternatively, have the patient tap the examiner’s palm every time a certain letter o the alphabet is mentioned. Many elements do require speci c attention and testing, as one may miss signi cant ndings or leave others poorly de ned. These are typically symptom-driven, as in a patient presenting with suspicion o intracranial disease, spinal cord disease, peripheral weakness or numbness, or multi ocal neurologic disease. I the patient cannot pay attention, as in the case o delirium, the examiner may erroneously assume that he or she has an underlying dementia. There ore, ormal neuropsychological testing is best delayed until the patient has recovered rom acute illness and the delirium has resolved. UNRESPONSIVENESS

CASE 104-4 A 62-year-old man is ound unresponsive. His cranial nerves are tested individually and are intact, with the exception o unequal pupils, corneal re exes, and abnormal eye movements. He does not respond to pain ul stimuli. Babinski sign is present on the le t. MRI reveals a basilar artery thrombosis.

Frequently, the exam is erroneously thought to be o little use in patients who are unresponsive or comatose. At the very least,

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CASE 104-6

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Magnetic resonance venography (MRV) shows a venous clot and stroke with hemorrhagic conversion. She is subsequently ound to have antiphospholipid antibody syndrome.

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pupillary, corneal, and gag or cough ref exes can be evaluated easily in the nonparalyzed patient. Facial strength, along with the motor and sensory systems, can be evaluated with response to pain ul stimuli. Coma can result rom two di erent localizations: bilateral cerebral hemispheric damage, as in head trauma or metabolic disturbances, such as hepatic encephalopathy or drug intoxication, and damage to the reticular activating system in the brainstem. Most cranial nerve nuclei (III to XII, except XI) are housed in the brainstem near the reticular activating system. I there are cranial nerve abnormalities, the lesion responsible or coma likely involves the reticular activating system, as in the patient vignette above. In the more common scenario where the cranial nerves are normal, bilateral hemispheric dys unction is likely the culprit.

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Atrophy Fasciculations Sensory symptoms and signs

Neuropathy Distal Decreased or absent

4

Weakness pattern Deep tendon re lexes

Motor Neuron Disease Variable Increased, normal, or decreased Yes Yes No

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TABLE 104-2 Patterns of Muscle Weakness

A 54-year-old man with a history o myocardial in arction and stroke complains o vertigo. He is recovering rom a recent upper respiratory in ection. The emergency department physician calls you to admit the patient or a possible brainstem stroke.

HEADACHE

CASE 104-5 A45-year-old otherwise healthy woman presents with progressive headaches and le t-sided weakness. She has had recent evers. Her exam reveals bilateral papilledema, in addition to mild le tsided weakness.

Headache is a common element in patients with various underlying intracranial processes. These patients may have normal exams or relatively nonspeci c exam ndings. The character o the headache and nature o its onset are very important. A moderate headache o subacute onset is evaluated di erently than a severe headache o acute onset. An exacerbation o a previously evaluated migraine syndrome may not warrant repeated imaging, but a sudden-onset “worst headache o my li e” certainly does. This patient has papilledema on exam, concerning or raised intracranial pressure, which may present solely with headache. Causes o high intracranial pressures include venous sinus thrombosis, cerebrovascular disease with edema, malignancy, meningoencephalitis, mass lesion, pseudotumor cerebri, and brain abscess. In these cases, historical elements such as blurred vision, diplopia, headache, and nausea will o ten be o more help in the di erential diagnosis than the exam. Signs in patients with headaches due to ocal lesions include a depressed level o consciousness, pupillary asymmetry, unilateral weakness, and pronator dri t. However, even large subdural hematomas may be missed on a thorough examination, requiring a high index o suspicion rom the history, and communication with amily members who may report a subtle personality change.

CASE 104-5 (continued) Further history reveals three spontaneous miscarriages. Over the next several hours, the patient develops bilateral weakness, increasing headache, and a le t-sided seizure that generalizes.

Vertigo is a source o requent consternation, as it may represent the common sequelae o an upper respiratory tract in ection, or a harbinger o li e-threatening posterior ossa disease. Key initial steps are to determine whether the patient has true vertigo, with the illusion o movement, or a di erent sensation, such as presyncope. Elements o the history and exam that suggest a central cause o vertigo, such as brainstem stroke, intracranial mass lesions, or multiple sclerosis, include headache, persistent symptoms, neck pain, visual disturbances, speech di culty, cranial nerve palsies, and ataxia. Horizontal nystagmus is common in both central and peripheral vertigo, but vertical nystagmus is more common with central rather than peripheral conditions. Hearing loss is uncommon with central disease.

CASE 104-6 (continued) The patient’s history is reassuring. The only nding on a detailed neurologic exam is two beats o horizontal nystagmus. He is sent home rom the emergency department and does well.

COMPLAINTS REFERABLE TO THE SPINAL CORD

CASE 104-7 A 32-year-old woman with a distant history o tuberculosis and recent treatment with prednisone or an asthma exacerbation presents with midback pain and vague complaints o dif culty walking, along with a sensation o her legs giving way. On examination, her gait is tentative, and Babinski signs are present bilaterally.

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Re lex Biceps Triceps Brachioradialis Abdominal

Peripheral Nerve Musculocutaneous Radial Radial Segmental cutaneous nerves

Patellar Achilles

Femoral Tibial

Nerve Root C5, C6 C7, C8 C5, C6 T8-T9 (above umbilicus); T10-T11 (below umbilicus) L3, L4 S1, S2

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TABLE 104-3 Tendon Reflexes and Their Associated Nerve Root Levels

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Few areas are more important in neurologic localization than the spinal cord. Because the spinal cord is tightly con ned in a bony canal, irreversible damage with pro ound consequences can be millimeters or minutes away. Historical eatures that increase the risk o spinal cord compression include recent trauma, metastatic cancer, myeloma, and systemic in ection, especially with bacteremia, which increases the risk o epidural abscess. Pain at the site o compression is usually the rst symptom. Patients may have radicular pain at the level o compression, o ten exacerbated by coughing or straining. Leg weakness and sensory disturbances are also common. Cauda equina involvement may produce bowel and bladder disturbances. Sensory testing must be per ormed to help de ne the level o involvement. This can be per ormed with a sa ety pin or tuning ork run quickly over the patient’s back. This brie examination is o immense value in determining what level should be imaged. Ref ex testing may also help to de ne the level, as well as the a ected side i disease is unilateral (Table 104-3). Weakness, hyperref exia, and Babinski signs may also be present.

CASE 104-7 (continued) The patient’s sensory exam reveals a clear change in sensation below T11. Subsequent evaluation con rms Pott’s disease o the spine.

TABLE 104-5 Grading of Deep Tendon Reflexes 4 3 2 1 0

Very brisk, o ten with clonus (record the number o beats) Brisk Normal Minimal Absent

o misdiagnosis is increased in patients with vague complaints or barriers to communication. Multi ocal disease calls or an even more care ul history and examination, as disease mani estations may be protean. Conditions such as polyarteritis nodosa, sarcoidosis, Sjögren syndrome, porphyria, and lead poisoning can be clinically con using even when disparate sensory and motor symptoms are not part o the clinical picture. When these are the presenting symptoms, the di culty in lesion localization may drive electrodiagnostic studies, as well as a wide-ranging laboratory evaluation. DOCUMENTING THE EXAMINATION When caring or patients with neurologic disease, documentation o the examination requires greater precision than “non ocal” and general terms such as “weak.” Whereas the sensory exam does not lend itsel well to quanti cation, the motor strength and ref ex testing do (Tables 104-4 and 104-5). It is important to record what areas are tested and the degree o weakness noted. This in ormation is especially valuable when patients have f uctuating symptoms either in the hospital or a ter discharge. Specialized instruments, such as the National Institutes o Health Stroke Scale (NIHSS), may be very help ul or the hospitalist (http:// www.ninds.nih.gov/doctors/NIH_Stroke_Scale.pd ). In addition to quanti ying the de cits in patients su ering acute stroke and determining eligibility or more aggressive intervention, the NIHSS is an excellent tool or documenting neurologic de cits. Many hospitals mandate recording o the NIHSS on admission and at intervals during a hospital stay. I the patient has a signi cant change, a covering physician or nurse will be able to quanti y the degree o di erence and determine whether additional interventions are needed. Free training courses are available online.

MULTIFOCAL DISEASE Multi ocal disease can be di cult to diagnose. Many neurologic diseases present with ill-de ned symptoms, particularly in the early stages. There is a tendency to label a patient as a malingerer in the absence o an easily discernible pattern or localizable lesion. This risk

TABLE 104-4 Grading of Muscle Strength (Modified Medical Research Council Scale) Grade 0 Grade 1 Grade 2 Grade 3 Grade 4Grade 4 Grade 4+ Grade 5

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No movement whatsoever Flicker or trace contraction Moves only when gravity is eliminated (in the horizontal plane only) Moves against gravity but not resistance Moves against gravity and light resistance Moves against gravity and moderate resistance Submaximal movement against resistance Full power

CONCLUSION The neurologic examination is key in determining the cause o neurologic complaints. While the potential range o evaluation can be daunting, a ocused examination that is in ormed by the history has a high yield. This is no less true or patients who are poorly responsive. By using standardized tools and scales, one can more easily communicate change and intervene with more certainty. With a core set o neurologic examination skills and knowledge, the practicing hospitalist plays a central role in the care o these patients.

SUGGESTED READINGS Biller J, Gruener G, Brazis P. DeMyer’s The Neurologic Examination: A Programmed Text, 6th ed. New York, NY: McGraw-Hill; 2011. Booth CM, Boone RH, Thomlinson G, et al. Is this patient dead, vegetative, or severely neurologically impaired? In: Simel DL, Rennie D, eds. The Rational Clinical Examination. New York, NY: McGraw-Hill; 2009:215-226. Chap. 17.

C H A P T E R 1 0 4 T h e N e u r o l o g i c E x a m i

Lanska DJ, Goetz CG. Romberg’s sign: development, adoption, and adaptation in the 19th century. Neurology. 2000;55:1201-1206.

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Tejus MN, Singh V, Ramesh A, Kumar VR, Maurya VP, Madhugiri VS. An evaluation o the nger f exion, Ho man’s and plantar ref exes as markers o cervical spinal cord compression. Clin Neurol Neurosurg. 2015;134:12-16.

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Lance JW. The Babinski sign. J Neurol Neurosurg Psychiatry. 2002;73:360-362.

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Smetana GW and Shmerling RH. Does this patient have temporal arteritis. In: Simel DL, Rennie D, eds. The Rational Clinical Examination. New York, NY: McGraw-Hill; 2009:643-656. Chap. 49.

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Goldstein LB, Simel DL. Is this patient having a stroke? In: Simel DL, Rennie D, eds. The Rational Clinical Examination. New York, NY: McGraw-Hill; 2009:627-641. Chap. 48.

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Rao G, Fisch L, Srinivasan S, et al. Does this patient have Parkinson disease? In: Simel DL, Rennie D, eds. The Rational Clinical Examination. New York, NY: McGraw-Hill; 2009:505-514. Chap. 38.

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Froehling DA, Silverstein MD, Mohr DN, Beatty CW. The Rational Clinical Examination. Does this dizzy patient have a serious orm o vertigo? JAMA. 1994;271(5):385-388.

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105

CHAP TER

Using Prognosis to Guide Treatment Rachelle E. Bernacki, MD, MS Joshua R. Lakin, MD

Key Clinical Questions

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1

How does the physician approach a patient with multiple comorbidities? How are they di erent than other patients?

2

How do multiple comorbidities and unctional status a ect a patient’s prognosis?

3

How does the physician take prognosis into account when ormulating treatment plans or patients?

CASE 105-1 A 79-year-old woman with moderately severe chronic diseases (obstructive pulmonary disease, osteoporosis, osteoarthritis, type 2 diabetes mellitus, and hypertension) was admitted to the hospital or a complicated urinary tract in ection. She had recently moved to the area and needed to establish primary care ollowing discharge. Her newly assigned primary care physician requested that “good maintenance medications”be prescribed or her chronic diseases prior to discharge. However, i the relevant clinical practice guidelines were ollowed, the patient would be prescribed 12 medications (her cost $406 per month) along with a complicated nonpharmacological regimen (see Table 105-1). The patient did not f nd these recommendations to be practical.

INTRODUCTION The remarkable success o medicine combined with improved living conditions in the last century has led to an increase in li e expectancy in the United States. In the 21st century, a 70-year-old woman in the top 25% percentile o health can expect to live an additional 21.3 years (see Figure 105-1). As more people are living into old age, the numbers o patients with multiple comorbitites are rising. In act, very ew patients have only hypertension or simply diabetes; many patients with chronic diseases have multiple comorbidities. In 2010, only 32% o Medicare bene ciaries had one or less chronic medical conditions and 37% had our or more. Health care costs or individuals with at least our chronic conditions accounted or 74% o Medicare’s annual spending. Comorbidity is associated with higher health care use, physical disability, polypharmacy/adverse drug events, poor quality o li e, and increased mortality. Improving care or this population is clearly important, but it is a challenge or physicians, including hospitalists, who need to balance and prioritize treatment o the acute conditions requiring hospitalization with the chronic morbidities that may complicate treatment. Until recently there have been ew guidelines on how to account or patients’ comorbidities and ormulate reasonable treatment plans. Care can be haphazard, scattered, and costly or the patient, provider and health care system. Some argue that the best way to approach the above patient is to consider her prognosis in making recommendations on how to treat her various conditions and take patient pre erences into account. To a large degree, how a medical team decides to treat a patient’s particular condition or comorbidity depends on the patient’s prognosis. “How long do I have?” is among the most common questions asked by patients. Prognosis is de ned as “a prediction o the probable course and outcome o a disease” or alternatively, “the likelihood o recovery rom a disease.” More simply put, the question is: “What can I expect with the uture o my illness?” which includes both the time rame and the unctional and experiential trajectory o the illness. Current textbooks o internal medicine present a diagnosisbased approach to disease and provide little in ormation about the prognosis o diseases. Prognosis guides individualized clinical decisions such as cancer screening or hospice, and identi es groups at high risk or poor outcomes in whom targeted interventions may be most use ul. Importantly, prognosis can provide the oundation or discussing goals o care. Many patients want to discuss prognosis with physicians, and

C H A P T E R 1 0 5 U s i n g P r o g n o s i s t o G u i d e T r e a t m e n

Treatment Regimen Based on Clinical Practice Guidelines or a Hypothetical 79-Year-Old Woman with Hypertension, Diabetes Mellitus, Osteoporosis, Osteoarthritis, and COPD* Time Medications† Other 7:00 a m Ipratropium metered dose inhaler Check eet 70 mg/wk o alendronate Sit upright or 30 min on day when alendronate is taken Check blood sugar 8:00 a m 500 mg o calcium and 200 IU o Eat break ast vitamin D 2.4 g/d o sodium 12.5 mg o hydrochlorothiazide 90 mmol/d o potassium 40 mg o lisinopril Low intake o dietary saturated at and cholesterol 10 mg o glyburide Adequate intake o magnesium and calcium Medical 81 mg o aspirin nutrition therapy or diabetes§ 850 mg o met ormin DASH§ 250 mg o naproxen 20 mg o omeprazole 12:00 pm Eat lunch 2.4 g/d o sodium 90 mmol/d o potassium Low intake o dietary saturated at and cholesterol Adequate intake o magnesium and calcium Medical nutrition therapy or diabetes§ DASH§ 1:00 pm Ipratropium metered dose inhaler 500 mg o calcium and 200 IU o vitamin D 7:00 pm Ipratropium metered dose inhaler Eat dinner 850 mg o met ormin 2.4 g/d o sodium 500 mg o calcium and 200 IU 90 mmol/d o potassium o vitamin D Low intake o dietary saturated at and cholesterol 40 mg o lovastatin Adequate intake o magnesium and calcium 250 mg o naproxen Medical nutrition therapy or diabetes§ DASH§ 11:00 pm Ipratropium metered dose inhaler As needed Albuterol metered dose inhaler

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TABLE 105-1 Treatment Regimen for Case 105-1

Abbreviations: ADA, American Diabetes Association; COPD, chronic obstructive pulmonary disease: DASH; Dietary Approaches to Stop Hypertension. *Clinical practice guidelines used: (1) Joint National Committee on Prevention, Detection. Evaluation, and Treatment o High Blood Pressure VII. (2) ADA; glycemic control is recommended; however, speci ic medicines are not described. (3) American College o Rheumatology; recent evidence about the sa ety and appropriateness o cyclooxygenase inhibitors, particularly in individuals with comorbid cardiovascular disease, led us to omit them rom the list o medication options, although they are discussed in the reviewed clinical practice guidelines. (4) National Osteoporosis Foundation; this regimen assumes dietary intake o 200 IU o vitamin D. (5) National Heart, Lung, and Blood Institute and World Health Organization. † Taken orally unless otherwise indicated. The medication complexity score o the regimen or this hypothetical woman is 14 with 19 doses o medications per day, assuming two as needed doses o albuterol metered dose inhaler plus 70 mg/wk o alendronate. § Dash and ADA dietary guidelines may be synthesized, but the help o a registered dietitian is speci ically recommended. Eat oods containing carbohydrate rom whole grains, ruits, vegetables, and low- at milk. Avoid protein intake o more than 20% o total daily energy; lower protein intake to about 10% o daily calories i overt nephropathy is present. Limit intake o saturated at ( 3.0 mg/dL Albumin 3.0-3.4 g/dL Albumin < 3.0 g/dL

G u i d e T r e a t m

Survival to discharge ollowing cardiac arrest occurring in the hospital is in requent. In a recent study examining 433,985 Medicare patients who underwent in-hospital CPR, 18.3% o patients survived to discharge. For some diseases such as cancer, the prognosis is poorer; a meta-analysis o survival rates or CPR revealed that 6.7% o cancer patients survived to discharge. Survival to discharge or ward cancer patients was better than ICU cancer patients: 10.1% versus 2.2%. CPR or hospitalized patients is associated with poor outcomes, as the cause o arrest is related to advanced li e-threatening illness rather than a reversible acute cardiopulmonary event (eg, arrhythmia). Even i the patient survives, he or she may then have signi cant morbidity including permanent neurological and unctional impairment, a act that should be included when having discussions about pre erences or CPR. The actual statistics about survival o CPR are in sharp contrast to what the general public sees. In a study o survival o CPR depicted on television, 75% o the patients survived the immediate arrest, and 67% appeared to have survived to hospital discharge. Thus, the portrayal o CPRon television may lead the public to have an unrealistic idea o CPR and its chances or success. Physicians should be aware o the images o CPRdepicted on television and the con usion these images may create when discussing pre erences about CPR with patients and amilies. Not only is prognosis important or planning, but patients may change decisions based on perception o prognosis. In a study o older adults, subjects were asked about pre erences or cardiopulmonary resuscitation (CPR). Be ore learning the true probability o

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Functional status is o utmost importance when estimating prognosis in older adults. In the Walter index (see Figure 105-4), measures o unctional status added important in ormation about risk or 1-year mortality beyond that provided by medical diagnoses or physiologic or laboratory measures. Functional status ref ects the severity and end result o many di erent illnesses and psychosocial actors. Hospitalists o ten do not routinely record unctional status or their patients, but it is important or considering a patient’s prognosis. A recent study con rmed the impact o unctional status on critically ill hospitalized patients, showing a two to three old increase in the risk o death or patients with prehospitalization disability.

■ CARDIOPULMONARY RESUSCITATION

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IMPORTANCE OF FUNCTIONAL STATUS

and the ECOG scale (Eastern Cooperative Oncology Group) (0 = normal; 5 = dead) are the most commonly used scales. A median survival o 3 months roughly correlates with a Karno sky score 3. Newer prognostic scales have also been developed. The simplest method to assess unctional ability is to ask patients: “How do you spend your time? How much time do you spend in bed or lying down?” I the response is >50% o the time and this is increasing, estimate the cancer patients’ prognosis at 3 months or less. An increasing number o physical symptoms, especially dyspnea, are also a good indication that time is short. The Palliative Per ormance Scale (PPS) uses ve observer-rated domains correlated to the Karno sky Per ormance Scale, commonly used to estimate prognosis in patients with cancer. The PPS is a reliable and valid tool and correlates well with actual survival and median survival time or patients (see Tables 105-2 and 105-3). It has been ound use ul or purposes o identi ying and tracking potential care needs o palliative care patients, particularly as these needs change with disease progression.

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cancer, creatinine, albumin, and ADL dependency at discharge), this prognostic index strati es older adults according to 1-year mortality a ter hospitalization. For example, our patient in Case 105-2 would receive one point or being male, two points or a history o congestive heart ailure, two points or being discharged to a skilled nursing acility, and two points or poor nutritional status (albumin 2.9) or a total o seven points (a patient with metastatic cancer receives eight points). His 1-year mortality is estimated at 68%. This study emphasizes the importance o considering multiple domains when assessing prognosis in older adults. Some hospices use the Walter criteria (>6 points) to enroll patients. In 2012, a systematic review identi ed 16 prognostic indices, including the Walter Index described above, that predict mortality in a variety o clinical settings; however, only two indices have independent validation. The most clinically use ul o these indices are available ree or use at www.ePrognosis.org. This website categorizes patients depending on their location. For hospitalized patients, the website provides an online calculator using the Walter Index and provides both numerical and visual representation o 1-year mortality. A recent study evaluating the use o this tool ound that 91% o users ound the tool to be use ul and 47% o health care pro essionals stated that the prognosis that they were presented a ected their clinical decision making.

Points 1 2 5 2 3 8 2 1 2

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Figure 105 4 Mortality at 1 year postdischarge. (Reproduced, with permission, rom Walter LC, et al. Development and validation o a prognostic index or 1-year mortality in older adults a ter hospitalization. JAMA. 2001;285:2987-2994. Copyright © 2001 American Medical Association. All rights reserved.) 759

PPS Level 100%

Ambulation Full

90%

Full

80%

Full

70%

Reduced

60%

Reduced

50%

Mainly Sit/Lie

40%

Mainly in Bed

30%

Totally Bed Bound

20%

Totally Bed Bound

10%

Totally Bed Bound

0%

Death

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TABLE 105-2 Palliative Performance Scale Activity & Evidence o Disease Normal activity &work No evidence o disease Normal activity &work Some evidence o disease Normal activity with E ort Some evidence o disease Unable Normal Job/Work Signi icant disease Unable hobby/house work Signi icant disease Unable to do any work Extensive disease Unable to do most activity Extensive disease Unable to do any activity Extensive disease Unable to do any activity Extensive disease Unable to do any activity Extensive disease -

Sel -Care Full

Intake Normal

Conscious Level Full

Full

Normal

Full

Full

Normal or reduced

Full

Full

Normal or reduced

Full

Occasional assistance necessary

Normal or reduced

Full or Con usion

Considerable assistance required

Normal or reduced

Full or Con usion

Mainly assistance

Normal or reduced

Total Care

Normal or reduced

Total Care

Minimal to sips

Total Care

Mouth care only

-

-

Full or Drowsy +/- Con usion Full or Drowsy +/- Con usion Full or Drowsy +/- Con usion Drowsy or Coma +/- Con usion -

Source: Ho F, et al. A reliability and validity study o the Palliative Per ormance Scale. BMC Palliat Care. 2008;4(7):10.

survival, 41% o subjects wanted CPR. A ter learning the true probability o CPR, 22% o subjects wanted CPR. I li e expectancy was less than 1 year 5% o subjects wanted CPR.

PRACTICE POINT

•

Survival o in-hospital CPR is low (18%) especially or those with diseases such as cancer (6.7% total, 2.2% or those with cancer in the ICU).

and this holds true even within more narrowly de ned areas such as “metastatic solid tumors.” The unctional status based tools described above can prove very use ul in this population. For example, or patients with metastatic cancers with longer survival times, such as prostate or breast cancer, a Karno sky Per ormance Scale o less than 60, correlates with a median survival o less than 6 months. This is in contrast to cancers with shorter survival times, such as pancreatic or biliary cancers, which have a median survival o less than 6 months with a much higher KPS score ( 1, the probability o disease goes up; or LR < 1, the probability o disease goes down. When the LR is close to 1, the probability o disease is unchanged because the nding is equally likely in patients with and without the disorder. The LR is more stable than sensitivity and speci city when the prevalence o disease changes because the direction o change is the same or the numerator and denominator o the LR. Unlike sensitivity and speci city (which limit the number o test results to just two levels, “positive” and “negative”), a LR may be generated or multiple levels o the diagnostic test result. The LR may be used to calculate the increase in probability o disease rom baseline prevalence with positive test (LR positive) and decrease in probability o disease rom baseline prevalence with negative test (using alternative LR negative) or any level o disease prevalence. The likelihood ratio may be used to shorten a list o diagnostic hypotheses because the pretest “odds” (the ratio o the probabilities or and against a diagnosis) o the target disorder multiplied by the likelihood ratio or the diagnostic test result equals the posttest odds or the target disorder. The LR allows you to carry out sequences o diagnostic tests. The posttest probability or one test becomes the pretest probability or a second, independent test with a distinct pathophysiology. For example, a result whose likelihood ratio is 2 increases the probability about 15%, 5 about 30%, and 10 about 45%. Likelihood ratios o 0.5 decrease the probability about 15%, 0.2 about 30%, and 0.1 about 45%. For diagnostic tests to be meaning ul, they should increase or decrease probability by at least 20% to 25% (corresponding to likelihood ratios with values >3 or 6.5 mEq/L. • QRS widening usually at K+ levels > 7 mEq/L with higher levels causing wider complexes. • Cardiac arrest due to ventricular brillation, asystole, or PEA arrest at K+ levels > 9 mEq/L. • QT intervals are normal or short unless there is concomitant hypocalcemia in which the QT can be prolonged. Hypokalemia • Marked QT prolongation with or without a prominent U-wave. • Reduced amplitude o T-waves and ventricular arrhythmias in severe hypokalemia. Hypothermia • Osborn waves, de ections at the junction o the QRS and the ST-segments can be seen in leads V2-V6. • Prolonged PR, QRS, and QT intervals. • Sinus bradycardia, slow atrial brillation, and variable heart block. • Shivering arti act can obscure ECG ndings, especially in the limb leads. Hypothyroidism The ECG ndings o hypothyroidism are varied and can occur due to reduced cardiac adrenergic activity, myocardial edema, and development o pericardial e usions. • Bradycardia. • Reduced amplitude o all ECG wave orms.

C H A P T E R 1 0 8 T h e R e s t i n g E l e c t r o c a r d i o

Drug therapy • Digitalis Intoxication: atrial tachycardia with variable AVblock, nonparoxysmal junctional tachycardias, second and third degree AVblock, sinoatrial block, ventricular arrhythmias (including bidirectional VT), and near regularization o the ventricular rate in the presence o atrial brillation. • Class IA agents (quinidine, procainamide, disopyramide): slight widening o the QRS at normal doses. In the setting o hypokalemia and bradycardia, quinidine can cause QT prolongation. • Class IB agents (lidocaine, mexiletine, tocainide): no e ect on ECG at therapeutic doses. • Class IC agents ( ecainide, propa enone): widening o the QRS and lengthening o the QTc interval due to QRS prolongation at normal doses. • Class III agents (sotalol, ibutilide, and do etilide): QT prolongation. • SSRI’s: QT prolongation, o ten in a dose-dependent manner. • Lithium: prolonged QT and T-wave abnormalities. • Tricyclic Antidepressants: sinus tachycardia, prolonged QRS complex, rst degree AVblock, prolonged QT interval, prominent R-wave in aVR. A QRS duration 160 milliseconds high risk o seizures and ventricular arrhythmias. • Carbamazepine: sinus tachycardia in massive overdose; bradyarrhythmias or AVconduction delay in elderly women with therapeutic or slightly elevated levels and abnormal renal unction.

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Stroke • ST-segment depression or elevation, T-wave inversions. U-waves, and/or prolongation o the QT interval in up to 75% o patients with subarachnoid hemorrhage and >90% o unselected patients with either ischemic stroke or intracerebral hemorrhage. • Varied other ECG changes including heart block and SVT can be seen with insular cortex in arcts.

r

A prolonged QT interval may predispose to torsades de pointes, a type o polymorphic VT characterized by a typical “twisting o the points.”

•

Increase in PR interval (due to sympathetic withdrawal and slower AVnodal transmission). Prolonged QT with accompanying T-wave inversions.

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QTCorrected = QT/(RR)1/2

•

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QT syndromes. Brugada syndrome is an inherited condition associated with sudden cardiac death and mutations linked to the SCN5A gene, encoding a cardiac sodium channel. Electrocardiographically, it is associated with RBBB with ST-segment elevation in leads V1-V3 (Figure 108-25). Prolongation o the QT interval may be either congenital or acquired. Congenital prolonged QT syndrome is the result o genetic mutations, most commonly in genes expressing ion channels. Acquired QT prolongation occurs as a result o electrolyte derangements or ingestion o QT-prolonging medications such as macrolides, luoroquinolones, and antipsychotics (Figure 108-26). The QT interval, measured rom the beginning o the QRS complex to the end o the T-wave in the lead with the longest interval, decreases as heart rate increases. The Bazett ormula o ers a mathematical means or relating the QT interval to heart rate as ollows:

Chronic obstructive pulmonary disease pattern • Pseudoin arct pattern: right atrial abnormality, vertical P and QRS axes, dominant S-waves across precordium, low voltage o R-wave in V6. • Features that speci cally suggest the presence o chronic obstructive pulmonary disease pattern disease i all present (>90% speci city and >50% sensitivity): 1. P-waves with a rightward axis in the range o +70° to +90° (ie, negative P-wave in aVL). This re ects that atrial activation is directed more in eriorly than usual while the ventricular activation is more superiorly and posteriorly than normal due to the vertical suspension o the heart in the midline. 2. The QRS complexes with low voltage in limb leads and precordial leads, re ecting increased lung volumes. 3. The QRS axis is superior with negative complexes (QS or rS) in in erior leads. 4. The precordial leads show predominant S-waves through V6. 5. The R-wave in V6 is 5 is hepatocellular and 45, Ferritin > 300)

E

Hemochromatosis

l

Travel, health care worker, drug use, sexual history HAVIgM HCVAb, consider RNA HBVsAb, sAg, c IgM HIV Immunocompromise CMVPCR, IgG EBVPanel HSVPCR

e

Alpha-1 Antitrypsin

v

Serum or urine HCG; CBC, LDH, haptoglobin, reticulocyte count

Pregnancy-related - Acute Fatty Liver of Pregnancy - HELLP Viral Hepatitis

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Primary Sclerosing Cholangitis Wilson Disease

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History o heavy or prolonged alcohol; serum alcohol level History o mushroom ingestion

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Alcoholic Hepatitis Amanita Phalloides

Diagnosis Antinuclear Ab Antismooth muscle Ab Anti liver-kidney microsomal Ab, IgG Cholangiogram with beaded appearance AP/bilirubin < 2 Ceruloplasmin, 24-h urine copper, Kayser Fleischer rings Alpha-1 antitrypsin SPEP

d

Cause Autoimmune Hepatitis

L

Diagnosis Serum acetaminophen level

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Cause Acetaminophen

H

C

TABLE 109-6 Causes of Hepatocellular Liver Injury

N-acetylcysteine should be administered in acetaminophen overdose to reduce hepatic injury; it is most bene cial i given within 8 hours o acetaminophen ingestion. Activated charcoal should be administered within 4 hours o ingestion, prior to NAC.

ALCOHOLIC HEPATITIS Alcoholic hepatitis should be considered in the patient with recent or prolonged heavy alcohol use, with or without ever, jaundice, and tender hepatomegaly, in patients with or without underlying alcoholic cirrhosis. The AST:ALT ratio is characteristically 2:1. Mortality in severe alcoholic hepatitis is high, with mortality o 34% at 28 days, and less than 25% survival at 6 months without treatment. The principles o management o alcoholic hepatitis are aimed at supportive care, diagnosing and treating concurrent in ection, and on whether to initiate AH speci c treatment. Patient with AH requently have coexisting in ection. Patients hospitalized with AH should undergo in ectious work-up, including cultures o blood and

urine and i present, ascites, and chest x-ray i there is clinical suspicion or pneumonia. Appropriate antibiotics should be initiated i an in ectious source is identi ed. There is no consensus on initiation o empiric antibiotics. The most widely utilized prognostic score in AH is the mDF, which was originally described in 1978 to identi y patients who may bene t rom corticosteroid therapy. MDF = 4.6 × [patient’s prothrombin time (seconds) – control prothrombin time (seconds)] + bilirubin (mg/dL) A score o equal or greater than 32 or presence o HE de nes severe AH. The mDF should be calculated in all patients presenting with AH, and speci c pharmacotherapy should be considered solely or patients with severe AH. Corticosteroids (40 mg prednisolone daily or 28 days, with or without a 2-week taper) and pentoxi ylline have been used to treat alcoholic hepatitis. Corticosteroids are contraindicated in signi cant in ection, renal ailure, or gastrointestinal bleeding. In the Steroids or Pentoxi ylline or Alcoholic Hepatitis (STOPAH) trial, there was a nonsigni cant trend toward improved 1-month survival o patients with severe AH and an increased risk o in ection in the prednisolone treated arm. There was no short or long-term survival bene t seen in the pentoxy ylline arm. In one recent systematic meta-analysis o 22 randomized controlled trials, corticosteroids demonstrated decreased short-term mortality, with no e ect on medium or 801

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long-term mortality. The addition o NAC has shown improved 1-month, but not 6-month, survival. Given the risk o in ection with corticosteroid treatment, the Lille score has been proposed to determine response to corticosteroid therapy. Calculated a ter 7 days, a score greater than 0.45 conveys a poor response to therapy and in these patients discontinuation o steroids should be considered. Six-month survival in steroid noresponders is extremely high (70%) but may be improved with early liver transplantation in highly selected patients with AH. Resource allocation in patients with active alcohol use varies among liver transplant centers. Lille score = 3.19 – 0.101 × age (years) + 0.147 × albumin on day 0 (g/L) + 0.0165 × the change in bilirubin between day 0 and day 7 o corticosteroid treatment (µmol/L) – 0.206 × renal insu ciency (rated as 0 i absent and 1 i present) – 0.0065 × bilirubin on day 0 (µmol/L) – 0.0096 × prothrombin time (seconds)

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Calculate the mDF in patients with suspected AH. In severe AH, mDF > 32 or presence o HE, consider treatment with corticosteroids (prednisolone 40 mg daily) i no contraindication, with or without NAC. Reassess response to corticosteroids a ter 1 week o treatment using the Lille score. I poor response (score > 0.45), discontinue therapy and consider evaluation by transplantation specialist, based on institutional practice.

ACUTE LIVER FAILURE It is critical to recognize ALF—coagulopathy and encephalopathy in a patient with no known liver disease—due to high morbidity and mortality associated with complications o ALF. While acetaminophen overdose, toxin ingestion and viral hepatitis are the most common causes, any o the etiologies presented in this chapter may cause ALF, and up to one- th o cases are idiopathic. Patients with ALF may present with hemodynamic instability and multiorgan ailure. Trans er to a liver transplant center and management in an intensive care unit is most appropriate to allow or serial laboratory testing and examination, particularly to identi y worsening encephalopathy and increased intracranial pressure, coagulopathy, bleeding, in ection, and concomitant organ ailure. Treatment is supportive and is aimed at addressing the complications o hepatic ailure (Table 109-7). In a prospective RCT by the National Institutes o Health, intravenous NAC administered to patients with nonacetaminophen induced ALF improved transplant ree survival (52% vs 30%, p = 0.010) in early stage ALF (grade I/II encephalopathy alone), and was well tolerated (Lee Gastroenterology 2009). Additionally, there was a trend toward shorter hospital stay by 4 days in the NAC treated group o patients. Consequentially, NAC should be administered to patients with nonacetaminophen ALF given the potential bene t with limited adverse e ects. In the setting o ALF, the clinician pursue early trans er to a transplant center. Serial calculations o prognostic scores, such as the MELD score, are used to predict which patients will have a high mortality without liver transplant. A patient meeting all King’s

TABLE 109-7 Organ-specific Management of Acute Liver Failure Organ System Neurologic

Complication(s) Cerebral edema and intracranial hypertension

Pulmonary

Mechanical ventilation or either airway protection rom altered mental status or due to respiratory ailure rom ALI/ARDS

Cardiovascular

Hypotension (hemodynamic collapse)

Renal

Acute kidney injury, volume overload, and metabolic disturbances

Management 1. Consider placing an intracranial monitor 2. Maintain a cerebral per usion pressure o 60-80 mm Hg 3. Maintain an ICP < 25 mm Hg 4. Maintain head o bed somewhat elevated (45°) 5. Medical management o elevated ICP (see Figure 158-1) 6. Avoid stimulation o patient 7. Serial neurologic examinations 8. Consider EEG 1. Lidocaine IVor endotracheal during intubation 2. Propo ol or sedation 3. Consider cis-atracurium paralysis 4. Either volume or pressure controlled ventilation 5. Low tidal volumes o 6 mL/kg o ideal body weight 6. Maintain maximal plateau pressure < 30 cm H2O 7. Avoid bronchoscopy 1. Arterial catheter or direct measurement 2. Fluid resuscitation (o ten less volume than is required with sepsis) 3. Vasopressor support with norepinephrine as irst choice 4. Avoid alpha-adrenergic agents 5. Consider a pulmonary artery catheter 6. Monitor mixed or central venous oxygen saturation 1. Early initiation o renal replacement therapy with CRRT pre erred over HD 2. Nephrology consultation 3. Bicarbonate bu ered hemo iltration 4. Renal ultrasound (Continued)

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ALI/ARDS, acute lung injury/acute respiratory distress syndrome; CMV, cytomegalovirus; CRRT, continuous renal replacement therapy; DVT, deep vein thrombosis; EEG, electroencephalogram; HD, hemodialysis; HSV, herpes simplex virus; ICP, intracranial pressure; PPI, proton pump inhibitor; TPN, total parenteral nutrition; VZV, varicella zoster virus.

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Management 1. Vitamin K10 mg SQ × 3 d 2. Avoid FFP unless there is bleeding, and monitor serial INR/PT/PTT 3. Trans use platelets based on Practice Point recommendations (p. 1293) 4. Subcutaneous heparin or DVT prophylaxis 5. Consider recombinant actor VII i placing an intracranial pressure monitor Bacterial and ungal 1. Maintain a low clinical threshold to culture and start empiric antimicrobials in ections; acute viral causes 2. Follow hospital protocols to reduce iatrogenic in ections rom central lines and o ALF catheters 3. Early antiviral therapy or acute hepatitis B, HSV, CMV, or VZV Relative adrenal 1. Maintain a low clinical suspicion i hypotension seems re ractory insu iciency 2. Consider stress dose steroid therapy Hypoglycemia, 1. Frequent serum glucose checks; dextrose-containing luids hypophosphatemia, 2. Bicarbonate bu ered solutions with CRRT hyponatremia, hypo3. Replete phosphorous, potassium, and magnesium or hyperkalemia, low 4. Treat hyperkalemia magnesium levels, metabolic acidosis 5. Early CRRT Stress ulcerations, severe 1. Early enteral eedings should be considered catabolic state 2. TPN i enteral eeds not possible (ileus, etc) 3. H2-blocker or PPI therapy

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In ectious Disease

Complication(s) Thrombocytopenia and coagulation abnormalities involving both a bleeding and thrombosis risk

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College Criteria (Table 109-8) has a likelihood ratio o 8.63 or a poor prognosis without liver transplant.

PRACTICE POINT

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All patients with ALF with stage I or II HE should receive NAC, regardless o etiology, to improve transplant ree survival. Patient with ALF should be evaluated early at a transplant center. The King’s College Criteria and MELD score may help in determining poor prognosis without liver transplant.

TABLE 109-8 King’s College Criteria—Prognostic Model for Determining Poor Outcome without Liver Transplantation in Acute Liver Failure (ALF) For acetaminophenInduced ALF Arterial pH < 7.3 OR All three o the ollowing: INR > 6.5 Serum creatinine > 3.4 mg/dL Grade III or IV encephalopathy

For nonacetaminophenInduced ALF INR > 6.5 OR Three out o ive o the ollowing criteria: Age < 11 or > 40 Serum bilirubin > 18 mg/dL Time rom jaundice to coma > 7 d INR > 3.5 Etiology non-A or non-B viral hepatitis OR drug-induced liver injury

SUGGESTED READINGS Altyar A, Kordi L, Skrepnek G. Clinical and economic characteristics o emergency department visits due to acetaminophen toxicity in the USA. BMJ Open. 2015;5(9):e007368. Bhatia V, et al. Predictive value o arterial ammonia or complications and outcome in acute liver ailure. Gut. 55;98:2006. Chalasani N, Fontana RJ, Bonkovsky HL, et al. Causes, clinical eatures, and outcomes rom a prospective study o drug-induced liver injury in the United States. Gastroenterology. 2008;135(6): 1924-1934, 1934.e1-4. Dart RC, Rumack BH. Acetaminophen (Paracetamol). In: Dart RC, ed. Medical Toxicology, 3rd ed. Philadelphia: Lippincott Williams & Wilkins; 2004. Dugum M, McCullough A. Diagnosis and management o alcoholic liver disease. J Clin Transl Hepatol. 2015;3(2):109-116. Lee WM, et al. Acute Liver Failure Study Group. Intravenous N-acetylcysteine improves transplant- ree survival in early stage non-acetaminophen acute liver ailure. Gastroenterology. 2009;137(3):856-64, 864. Leise MD, Poterucha JJ, Talwalkar JA. Drug-induced liver injury. Mayo Clin Proc. 2014;89(1):95-106. Mathurin P, Moreno C, Samuel D, et al. Early liver transplantation or severe alcoholic hepatitis. N Engl J Med. 2011;365:1790-1800. Mathurin P, O’Grady J, Carithers RL, et al. Corticosteroids improve short-term survival in patients with severe alcoholic hepatitis: meta-analysis o individual patient data. Gut. 2011;60:255-260. Polson J, Lee WM. AASLD position paper: the management o acute liver ailure. Hepatology. 2005;41:1179-1197. Singh S, Murad MH, Chandar AK, et al. Comparative e ectiveness o pharmacological interventions or severe alcoholic hepatitis: a 803

systematic review and network meta-analysis. Gastroenterology. 2015;149(4):958-70.e12.

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Smilkstein MJ, Knapp GL, Kulig KW, Rumack BH. Ef cacy o oral N-acetylcysteine in the treatment o acetaminophen overdose. Analysis o the national multicenter study (1976 to 1985). N Engl J Med. 1988;319(24):1557.

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Thursz MR, Richardson P, Allison M, et al. Prednisolone or pentoxi ylline or alcoholic hepatitis. N Engl J Med. 2015;372:1619-1628.

ONLINE RESOURCES LiverTox: http://livertox.nih.gov

110

CHAP TER

Pulmonary Function Testing Joseph J. Miaskiewicz, Jr., MD, FHM

Key Clinical Questions 1

What in ormation do pulmonary unction tests provide in addition to the history and physical examination?

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What speci ic tests might you order to evaluate the acutely ill hospitalized patient and how does each test in luence diagnostic evaluation or management?

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What operations require preoperative pulmonary unction tests as part o the preoperative evaluation?

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What are the predictors o increased postoperative risk?

INTRODUCTION Pulmonary unction tests (PFTs) objectively assess lung unction. Along with measurement o arterial blood gases (ABGs), PFTs are used to evaluate how much a patient's symptoms or known lung disease impairs daily activities and the tests are help ul in management, such as when to treat a patient and in what setting. The purpose o PFTs is to evaluate dyspnea by assessing the mechanical unction o the respiratory system, to quantitate the loss o lung unction, and to monitor disease progression and response to treatment. PFTs also predict postoperative risk o pulmonary complications and which patients will likely have adequate pulmonary unction a ter lung resection. Serial evaluations monitor respiratory muscular strength in progressive neuromuscular diseases such as Guillain-Barre, myasthesia gravis, and muscular dystrophy. PFTs estimate the ollowing: 1. Volumes or the ability o the lungs to ully expand (TLC, FRC, RV). 2. Flow rates or the rate o in ow and out ow o air (FEV1, orced expiratory ow [25%-75%]). 3. Maximum voluntary ventilation or air ow through major airways by rapid inspiration and expiration maneuvers (MVV). 4. Maximum inspiratory and expiratory pressure, a measure o respiratory muscle strength (Pi[max], Pe[max]). 5. Di using capacity (DLCO) or measurement o the ability o oxygen to get into the blood. Interpretation will be (1) normal, (2) obstructive, (3) restrictive, or (4) combined obstructive and restrictive. For the majority o PFTs to be meaning ul, patients must be able to physically per orm the tests and to ollow instructions. With the exception o oximetry, ABGs, and simple spirometry, PFTs are usually per ormed in the outpatient setting. Hospitalists should be able to (1) recognize patterns o pulmonary involvement when they review outside medical records, (2) know when to order speci c tests to evaluate acutely ill patients, and (3) avoid unnecessary ordering o PFTs when they are o limited utility in hospitalized patients. COMPONENTS OF TESTING PFTs will detect signi cant increased resistance to air ow (airway obstruction) and increased resistance to expansion (parenchymal disease, weakness o respiratory muscles or abnormalities o the chest wall or diaphragm). ABGs supplement PFTs by measuring the e ect o pulmonary and other illnesses on oxygenation and ventilation (Figure 110-1).

■ VOLUMES TLC = Total lung capacity or the total volume o gas within the lungs a ter a maximal inspiration RV= Residual volume or the volume o gas remaining in the lungs a ter a maximal expiration VC = Vital capacity or the volume o gas expired a ter a maximal inspiration ollowed by a maximal expiration FRC = Functional residual capacity or the volume o gas within the lungs at the end o expiration during normal tidal breathing at rest To quantitate VC, ask the patient to breathe into a spirometer and obtain a spirometric tracing. To quantitate RV, FRC, and TLC, other methods such as dilution tests or body plethysmography are 805

IC 72% VC

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Figure 110 1 Lung Volumes. (Reproduced, with permission, rom Weinberger SE. Principles of Pulmonary Medicine, 4th ed. Philadelphia: Saunders; 2004.)

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needed to measure the amount o air le t in the lungs. These measurements require signi cant expertise on the part o the respiratory therapist in the PFT laboratory and maximal patient cooperation and ability to ollow instructions. Inert gas dilution may underestimate lung volumes when there is air ow obstruction in patients who have air spaces such as bullae within the lung that do not communicate with the bronchial tree. Body plethysmography may overestimate lung volumes in air ow obstruction but may provide a more accurate measurement o intrathroacic gas volume in patients with noncommunicating airspaces within the lung. Most di use lung disease is associated with decreased lung volumes. Restrictive PFTs means limitation to ull expansion o the lungs. Volumes are decreased but ow rates are normal. Interstitial lung disease has reduced lung compliance and a restrictive de ect. PFTs will reveal a decreased TLC, FRC, and RV. Although FEV1 and FVC may be decreased secondary to decreased volumes, the FEV1/FVC ratio is normal or increased. When the TLC and VC are decreased, the di erential diagnosis includes restrictive lung disease (pulmonary brosis) or loss o lung volume (surgery, diaphragmatic paralysis, or skeletal problems). Decreases in the TLC, RV, and FRC can be interpreted as mild (60%-80% reduction), moderate (40%60% reduction) or severe ( 80 y

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Doe s this pa tie nt phys ica l exa mina tion s ugge s t the pos s ibility of s e ptic a rthritis ? • J oint wa rmth, pa in, swe lling, re s tricte d motion • Monoa rthritis • Tra uma with joint e ffus ion • Monoa rthritis in a pa tie nt with chronic a rthritis • Polya rthritis , e s pe cia lly in pa tie nts with impa ire d immunity • Sa croilia c a nd s te rnoclavicula r involve me nt, e s pe cia lly in IV drug us e rs • S kin le s ions (porta l of e ntry, clinica l syndrome of dis s e mina te d GC), s igns of sys te mic illne s s

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Doe s this pa tie nt re quire ima ging prior to a rthroce nte s is ? • Tra uma • S te rnocla vicula r joint infe ctions to look for me dia s tina l exte ns ion • Os te omye litis • Sa croilia c joint infe ction to look for pe lvic involve me nt

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Doe s this pa tie nt re quire e me rge nt s pe cia lty cons ulta tion? • S us pe cte d pros the tic joint infe ction (orthope dics ) • J oints ordina rily not a s pira te d by inte rnis ts (hip, s a croilia c, s ma ll joints of ha nd, foot, e tc) • S ma ll e ffus ions, unce rta inly a bout be s t dia gnos tic a pproa ch

Wha t othe r s tudie s s hould be pe rforme d a t the s a me time a s a rthroce nte s is in pa tie nts s us pe cte d of having s e ptic a rthritis ? • Blood culture s, pos s ibly e choca rdiogra phy (e ndoca rditis ) • Pe riphe ra l CBC a nd diffe re ntia l, infla mma tory ma rke rs (not s pe cific but e leva te d WBC with le ft s hift or e leva te d ES R, CRP a t the be ginning of tre a tme nt may he lp tra ck re s pons e to tre a tme nt) • For pa tie nts s us pe cte d of GC a rthritis s a mple s of GU, re ctum, oropha rynx (a s synovia l fluid culture s pos itive in 40% cases); ever may be associated with other conditions that cause joint pain, including gout Always contact orthopedic service i concern about a septic prosthetic joint Comments Steroid injection o a joint, tendon sheath, or bursa may provide pain relie without signi icant side e ects and shorten LOS Even a small dose o cortisone can be disastrous; steroids can also exacerbate glaucoma and ↑ blood sugars in diabetics No literature to support this theory; risk o not aspirating a septic joint outweighs risk Possibility o making a closed racture an open one Severe thrombocytopenia is most worrisome; most joints can be sa ely aspirated but i INR excessive or i hemophilia, partial correction may be appropriate (continued)

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Complications during Procedure Complications after Procedure

TABLE 127-2 Technical Tips Properly position patient under locally sterile conditions, taking the time to ensure all com ortable be ore proceeding Ensure an almost painless procedure

Select easiest location

Dry tap

H A P T E

A ected joint should be closely ollowed during treatment or recurrent signs and symptoms o in ection Septic joints may require repeated irrigation and drainage even a ter appropriate antibiotic therapy and initial drainage

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Reaccumulation o e usion, skin atrophy a ter steroid injections

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Comments Comments Plain ilms, CT, MRI, or radionuclide scanning cannot distinguish between septic and nonin ectious causes o synovitis. Only arthrocentesis will guide management

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Diagnostic Arthrocentesis Plain Radiographs Plain ilms are not essential in uncomplicated septic arthritis but may identi y complicating actors. Plain radiographs may identi y oreign bodies, osteomyelitis, periarticular so t tissue swelling seen in early septic arthritis, joint space loss, periosteal reaction, marginal and central erosions, destruction o subchondral bone Advanced Imaging CT and MRI nonspeci ic joint in lammation, e usion, subchondral cysts, articular cartilage destruction Trauma, pain, bleeding, in ection

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TABLE 127-1 Basic Consideration (Continued)

TABLE 127-3 Normal Test Results Patient lying on his back, with the a ected knee in a very slight passive lexion, obtained by placing a rolled towel under knee (see Figure 127-2) Reduce burning sensation o cutaneous injection o xylocaine by warming vial between palms; may also use ethyl chloride spray Approach knee either medially or laterally. Aim needle parallel to and just in erior to the patella so that it slips in, just underneath, into the joint itsel Per orm with CT or US guidance, consider specialty assistance

Test Obtain cell count, di erential, Gram stain, culture o synovial luid and crystals

Normal Value Insu icient luid to tap Synovial luid normally clear, colorless 80%, and the speci icity approaches 100%. Heterophile antibodies persist or up to 1 year a ter acute EBV in ection. Epstein-Barr virus speci c antibody assays are use ul in patients with negative heterophile antibodies (see Figure 198-1). The viral capsid antigen (VCA) antibody test measures either speci c immunoglobulin G (IgG) or IgM antibodies. Epstein-Barr nuclear antigen antibody (EBNA) test measures IgG, which rises during convalescence and stays elevated or li e. Early antigen antibody assay (EA–D)

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Figure 198 1 Serologic titers distinguish primary infection from remote infection. Immunoglobulin G (IgG) anti-viral capsid antigen (VCA) and IgM anti-VCA rise in concert with symptoms of primary infection and a positive heterophile test. After symptoms resolve, remote infection is characterized by Epstein-Barr nuclear antigen (EBNA) and IgG anti-VCA without early antigen (EA), although EA and IgM may reappear with or without symptoms on viral reactivation or Epstein-Barr virus–related neoplasia. (Reproduced, with permission rom the American Society or Investigative Pathology, rom Gulley M, et al. J Mole Diagn. 2008;10:272-292.)

C H A P T E R 1 9 8 V i r a l I

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Most patients with in ectious mononucleosis have a good prognosis and recover quickly. However, some cases can be severe and last or several months. A minority o patients develop chronic atigue syndrome, which may be more common in women and in those with pre-existing mood disorders. I airway obstruction or di culty breathing is observed, tracheotomy or endotracheal intubation should be considered. I splenic rupture has occurred, admission or attempted splenic preservation or splenectomy will be necessary.

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■ TREATMENT OPTIONS Supportive care with rest, uids, and moderate doses o acetaminophen, ibupro en, or other anti-in ammatories is the mainstay o care or in ectious mononucleosis. Warm saltwater gargles may relieve the discom ort o sore throat. The use o steroids or EBVassociated in ectious mononucleosis remains controversial. A recent meta-analysis suggests that there is insu cient evidence or its use in routine cases (Table 198-2). Many clinicians use corticosteroids in mononucleosis complicated by impending airway obstruction, autoimmune hemolytic anemia, thrombocytopenia, aplastic anemia, or neurologic complications, but the evidence to support its use in these settings is not robust. Impending airway obstruction, as de ned by di culty breathing, mandates admission to the hospital and close observation. Otolaryngology consult should be considered in these patients. The clinical bene t o acyclovir or treating acute in ectious mononucleosis remains unclear based on published studies.

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antibiotics Airway obstruction Splenomegaly and splenic rupture Splenic in arct Autoimmune hemolytic anemia Thrombocytopenia Aplastic anemia Hepatitis and cholestasis Meningoencephalitis or Guillain-Barré syndrome Hemophagocytic syndrome Malignancy (Hodgkin lymphoma; Burkitt lymphoma in A rica; nasopharygeal carcinoma in Asia; CNS lymphoma in AIDS; lymphoproli erative disease in transplant patients)

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TABLE 198-1 Complications of Epstein-Barr Virus Associated Mononucleosis

is usually positive during acute in ection. Polymerase chain reaction (PCR) assays are available, but rarely used in diagnosing in ectious mononucleosis. Epstein-Barr virus does not grow in routine tissue culture.

■ COMPLICATIONS Airway obstruction with acute in ectious mononucleosis is rare but serious. It usually requires close observation, with the ability to do emergent tracheotomy or endotracheal intubation. Splenic rupture presents with acute abdominal pain (or, rarely, le t-sided chest pain) and symptoms and signs o hypovolemia. Kehr’s sign (radiation o pain to the le t shoulder) is present in 50% o cases. Splenic rupture may be spontaneous or due to trauma, and usually occurs within 3 weeks a ter clinical symptoms have begun. Computed tomography o the abdomen and surgical consultation should be obtained i the diagnosis is suspected. Hemodynamically unstable patients should undergo splenectomy. In stable patients, close observation with nonoperative management or spleen-sparing interventions such as partial splenectomy, splenorrhaphy, and splenic artery embolization may be considered. Other complications that may require subspecialty consultation are autoimmune hemolytic anemia, encephalitis, and pneumonitis. Generalized rash may appear

TABLE 198-2 Infectious Mononucleosis and Corticosteroids • Randomized trials: 6 • Number o children and young adult patients: 268 • Treatment: acyclovir/valacyclovir (2/6)

Prednisone/prednisolone × 5-10 d • Result: “modest” clinical bene it, no signi icant reduction in duration o illness or days missed rom school or work, no di erence in relapse rate Data rom McGee S, Hirschmann J. Use o corticosteriods in treating in ectious diseases. Arch Intern Med. 2008;168(10):1034-1046.

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■ DISCHARGE CHECKLIST • Has the patient been counselled about physical activity? Individu-

als who play contact sports should avoid participation or at least 3 weeks, when they may resume noncontact training. Those who do weight li ting or strenuous contact sports should wait at least 1 month a ter their illness began. In selected cases, it may be useul to obtain an ultrasound at 3 weeks a ter the onset o illness to document resolution o splenomegaly and assess suitability to return to athletic activity, but this practice is not accepted by many individuals. • Has the patient been counselled about prognosis? In most patients, energy level is back to normal by 1 month, but atigue may take months to resolve in some patients. VARICELLA-ZOSTER VIRUS

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Varicella (chickenpox) is the primary in ection with varicella-zoster virus (VZV). It usually occurs in childhood, in temperate climates, and in adolescence or young adulthood in the tropics. Be ore the introduction o the varicella vaccine in 1996, there were an estimated 4 million cases o chickenpox in the United States each year. Since the introduction and widespread use o the vaccine in childhood, the incidence o chickenpox has been reduced in many populations by as much as 90%.

■ PATHOPHYSIOLOGY Primary in ection with VZV occurs in the nasopharynx, with spread to lymphoid tissue and memory CD4+ T-cells. Skin involvement develops within the rst ew days ollowing in ection. Cell- ree virus is present in skin vesicles, and can in ect sensory nerves, resulting in virus latency in sensory ganglia. Latent VZV genomes are localized to 75 y o age, 300 mg daily in divided doses 3600 mg daily (1200 mg 3 times daily); reduce i renal unction is impaired

Nausea/vomiting, constipation, sedation, dizziness, seizures, postural hypotension Sedation, dizziness, peripheral edema

75 mg at bedtime or 75 mg twice daily

Increase by 75 mg twice daily every 3 d as tolerated Increase by 25 mg daily every 2-3 d as tolerated

600 mg daily (300 mg twice daily); reduce i renal unction is impaired 150 mg daily

Sedation, dizziness, peripheral edema

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Sedation, dry mouth, blurred vision, weight gain, urinary retention §

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Tricyclic antidepressants, especially nortriptyline †

Most Common Adverse Effects Nausea/vomiting, constipation, sedation, dizziness

Consider lower starting dosages and slower titration or rail and elderly patients (eg, 5 mg twice daily or oxycodone); dosages given are or short-acting ormulations. † Consider lower starting dosages and slower titration or rail and elderly patients (eg, 10 mg at bedtime or tricyclic antidepressants). § Consider a screening electrocardiogram or patients ≥40 y o age. As adapted rom Dworkin RH, et al. with permission rom Clin Infect Dis. 2007;44:S1-S26. University o Chicago Press. © 2006 by the In ectious Diseases Society o America. *

P os the rpe tic ne ura lgia

Cons ide r non-pha rma cologica l tre a tme nts (phys iothe ra py, e motiona l s upport e tc.)

Firs t-line monothe ra py: TCA, ga ba pe ntinoid, topica l lidoca ine P a rtia l re s pons e to tre a tme nt

No tole ra bility Alte rna tive firs t-line monothe ra py (TCA, ga ba pe ntinoid e tc.)

Alte rna tive firs t-line monothe ra py (TCA, ga ba pe ntinoid e tc.)

No tole ra bility

P a rtia l re s pons e to tre a tme nt

Cons ide r opioid the ra py

Combine firs t-line drugs No tole ra bility/pa rtia l

Combine drugs a t re duce d dos e s Add opioid the ra py

Figure 198 3 Algorithm for treating postherpetic neuralgia (PHN). (Reproduced rom Galvez R, Redondo M. Evidence-based treatment o postherpetic neuralgia. In: Magel GD, ed. Herpesviridae-A Look Into This Unique Family of Viruses. InTech; 2012.) Available rom http://www .intechopen.com/books/herpesviridae-a-look-into-this-unique- amily-o -viruses/evidence-based-treatment-o -postherpetic-neuralgia.) 1600

INFLUENZA

■ INTRODUCTION/EPIDEMIOLOGY In uenza occurs worldwide in yearly outbreaks, mainly during winter months. It is caused by in uenza A or B viruses. When signi cant changes occur in both sur ace proteins, hemagglutinin and neuraminidase, worldwide pandemics can occur, as recently observed with the novel A/H1N1 virus. Once an outbreak begins, it usually spreads in a community over 8 to 12 weeks and becomes the major cause o acute upper and lower respiratory tract illnesses. In ection with epidemic strains is common in school-age children. However, increased mortality occurs primarily in the elderly. Transmission occurs by aerosols or droplets generated during coughing or sneezing. In the United States, an average o 20,000 to 40,000 deaths and 300,000 hospitalizations occur annually with in uenza epidemics. In April 2009, the rst case o novel H1N1 virus was recognized in Mexico. Over the next ew months, 41 countries reported cases. The World Health Organization declared that a pandemic situation was in ef ect in June 2009 (see Table 198-7).

■ PATHOPHYSIOLOGY There are three types o in uenza viruses: A, B, and C. Only in uenza A viruses have pandemic potential. Eight gene segments encode 10 or 11 proteins. Minor changes, or antigenic dri t, occur in the surace proteins each year. Major changes, or antigenic shi t, occur every 10 to 20 years in the viral sur ace hemagglutinin and neuraminidase. The updated yearly vaccine is based on the observed antigenic dri t. In uenza viruses spread by respiratory secretions to susceptible hosts. Respiratory symptoms are secondary to dys unction o cells and release o in ammatory mediators. The incubation period is rom 18 to 72 hours.

■ CLINICAL PRSENTATION The acute onset o ever and cough suggests in uenza, but it is nonspeci c, as other respiratory viruses may have a similar presentation.

TABLE 198-7 Pandemic H1N1 Influenza • First reported case in Mexico, March 2009 • Pandemic declared by the World Health Organization

in June 2009 • Novel H1N1 is quadruple reassortment o two swine strains, one human strain, and one avian strain o in luenza • Spread throughout the United States in all 2009 • Monovalent vaccine developed and distributed in 2009

C H A P T E R 1 i r a l I n e c t i

Pharyngitis and myalgias are common. Acute HIV syndrome can be mistaken or an in uenza-like illness. Primary in uenza pneumonia is a serious complication in a minority o patients with acute in uenza illness. In uenza can lead to secondary bacterial pneumonia, or a mixed picture o both viral and bacterial pneumonia (Table 198-8). Streptococcus pneumoniae is the most common bacterial pathogen isolated ollowing acute in uenza. However, Staphylococcus aureus pneumonia is diagnosed with increased requency in patients ollowing recent in uenza in ection. Other potentially li e-threatening conditions associated with in uenza in ection include myositis, rhabdomyolysis, CNS involvement, and myocarditis.

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coronavirus/rhinovirus less common • Increased requency in elderly • Cause up to 10%-30% o community-acquired pneumonia

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• Respiratory syncytial virus, parain luenza virus, and

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varicella-immune caregivers until crusting occurs. Skin lesions take up to 3 weeks to heal, and may o ten look worse in the second and third week as they crust over. Viral shedding rom skin lesions occurs until they become crusted over.

• In luenza viruses A and B most common

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Dissemination Hepatitis Pneumonitis Encephalitis/CNS and peripheral vasculopathy Postherpetic neuralgia

TABLE 198-8 Viral Causes of Pneumonia

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TABLE 198-6 Complications of Varicella-Zoster Virus Infections

■ DIAGNOSIS In uenza-like illness is associated with ever, sore throat, cough, and systemic complaints. During an outbreak o in uenza in a community, ebrile acute respiratory tract illness can be assumed to be due to in uenza virus. There are a number o rapid antigen tests that vary in sensitivity between 40% and 60% in adults. These rapid antigen tests are more sensitive in children because o the increased viral excretion in younger patients. Other diagnostic tests are indirect uorescent antibody (IFA) and direct uorescent antibody (DFA), as well as PCR and viral culture. Polymerase chain reactionis highly sensitive and speci c, but it o ten requires at least a day or results and is not readily available in many laboratories. Viral cultures are also sensitive and speci c, but they take several days be ore giving a positive result. In uenza serology is available, but is mainly o epidemiologic utility. Who should be tested or in uenza virus? During a communitywide outbreak o in uenza, patients with underlying disease and in uenzalike illness (ILI) should be tested or the presence o in uenza virus. In individuals who are immunocompetent and present with an ILI, testing or the presence o virus is not usually indicated. However, all hospitalized patients with ILI should be tested or the presence o in uenza virus. A positive rapid antigen test can be used to make decisions about speci c antiviral therapy. A negative rapid antigen test does not exclude in uenza in a patient with a high pretest probability. I a rapid antigen test is negative in a hospitalized patient is thought to have an ILI, then a specimen should be sent or urther testing, such as viral culture or PCR, and empiric antiviral therapy should be initiated. I PCR results are negative, therapy can be discontinued.

■ TRIAGE/HOSPITAL ADMISSION Patients with acute respiratory tract illness during an in uenza outbreak should be considered or hospital admission i they are elderly or too weak to care or themselves at home, have an underlying condition such as chronic obstructive pulmonary disease or congestive heart ailure, or there is a clinical suspicion or pneumonia. During an in uenza epidemic, it is important to triage as many patients as possible or care at home.

■ TREATMENT OPTIONS Several antiviral agents are currently approved or use in acute in uenza illness. The adamantanes, amantadine and rimantadine, are only active against in uenza A viruses. Because widespread 1601

Antiviral Amantadine Rimantadine

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TABLE 198-9 Antivirals for Influenza Virus Infections

Zanamivir

Dosage (5 d) 100 mg/d orally 100 mg/d orally 75 mg twice/d orally 2 inhalations twice/d

Side Effects CNS, GI CNS, GI GI Bronchospasm

resistance to the adamantanes has emerged among recent isolates o in uenza A, these antivirals are no longer used. The neuraminidase inhibitors oseltamivir and zanamivir are active against both in uenza A and B viruses. Resistance to the neuraminidase inhibitors has been described in previous years. However, over 98% o recent H1N1, H3N2, and in uenza B isolates are sensitive to oseltamivir (Table 198-9). Zanamivir resistance has been reported rarely.

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Activity In luenza A only In luenza A only In luenza A and B In luenza A and B

■ COMPLICATIONS Pneumonia is a serious complication o acute in uenza in ection. Primary in uenza pneumonia, although rare, is a serious cause o increased mortality. Clinically, the patient presents with cough and dyspnea. A chest radiograph will reveal dif use in ltrates or an acute respiratory distress syndrome (ARDS) pattern (Figure 198-4). Elderly patients and those with cardiovascular disease constitute the highest risk groups. The mortality rate in acute in uenza pneumonia is high. Secondary bacterial pneumonia can occur 2 to 3 weeks a ter the onset o in uenza symptoms. S. pneumoniae or S. aureus (including methicillin-resistant S. aureus [MRSA]) are the most commonly identi ed bacterial pathogens. Mixed viral and bacterial pneumonia has also been described ollowing acute in uenza. Another uncommon complication o in uenza in ection is myositis (Table 198-10). This occurs more commonly with in uenza B than with in uenza A, and is more common in children. Myoglobinuria and rhabdomyolysis have also been reported ollowing acute in uenza in ection. CNS complications are also rarely reported. These include encephalitis, transverse myelitis, and Guillain-Barré syndrome.

■ DISCHARGE PLANNING • Patients should be cautioned that, although the prognosis is

good in acute in uenza, malaise and atigue may persist or some time. • I the patient is a nursing home resident, have nursing home personnel been contacted to take measures to protect other residents rom an outbreak o acute in uenza?

TABLE 198-10 Influenza Virus–Associated Myositis • In luenza type A > B • Mostly in school-age children • Cal muscles commonly involved • Increased creatine kinase levels • Begins during convalescence • Sel -limited • Antivirals

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Figure 198 4 Chest radiographs of a hospitalized patient with novel H1N1 pneumonia and acute respiratory distress syndrome over 48 hours. (Courtesy o Venkata Bandi, Ben Taub Hospital, Houston, Texas.)

SUGGESTED READINGS Bader MS. Herpes zoster: diagnositic, therapeutic, and preventive approaches. Postgrad Med. 2013;125:78-91. Bruxelle J, Pinchinat S. Ef ectiveness o antiviral treatment on acute phase o herpes zoster and development o post herpetic neuralgia: review o international publications. Med Mal Infect. 2012;42:53-58. Canadian Pain Society Study Day Participants. Sa ety and ef ectiveness o the herpes zoster vaccine to prevent postherpetic neuralgia. 2015;20:46-47. Chiang F, Panyaping T, Tedesqui G, et al. Varicella zoster CNS vascular complications. A report o our cases and literature review. Neuroradiol J. 2014;27:327-333. Chovel-Sella A, Ben Tov A, Lahav E, et al. Incidence o rash a ter amoxicillin treatment in children with in ectious mononucleosis. Pediatrics. 2013;131:e1424-e1427. Di Lernia V, Mansouri Y. Epstein-Barr virus and skin mani estations in childhood. Int J Dermatol. 2013;52:1177-1184.

C H A P T E R 1 9 8 V i r a l I n e c t i o

Mertz D, Kim TH, Johnstone J, et al. Populations at risk or severe or complicated in uenza illness: systematic review and meta– analysis. BMJ. 2013;347: 5061.

Viasus D, Oteo Revuelta JA, Martinez-Montauti J, Carratalà J. In uenza A(H1N1)pdm09–related pneumonia and other complications. Enferm Infecc Microbiol Clin. 2012;30(Suppl 4):43-48.

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Galvez R, Redondo M. Evidence-based treatment o postherpetic neuralgia. In: Magel GD, ed. Herpesviridae-A Look Into This Unique Family of Viruses. InTech; 2012. Available rom http://www. in t e ch o p e n .co m / b o o ks/ h e rp e svirid ae -a-lo o k-in t o -t h isu n iq u e - am ily-o -viru se s/ e vid e n ce -b ase d -t re at m e n t-o postherpetic-neuralgia.

Muthuri SG, Myles PR, Venkatesan S, Leonardi-Bee J, NguyenVan-Tam JS. Impact o neuraminidase inhibitor treatment on outcomes o public health importance during the 2009-2010 in uenza A (H1N1) pandemic: a systematic review and meta-analysis in hospitalized patients. J Infect Dis. 2013;207: 553-563.

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Estabragh ZR, Mamas MA. The cardiovascular mani estations o in uenza: a systematic review. Int J Cardiol. 2013;167:2397-2403.

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199

CHAP TER

LYME DISEASE

■ EPIDEMIOLOGY

1

Which patients with tickborne diseases should be hospitalized?

2

How are Lyme disease, babesiosis, ehrlichiosis, anaplasmosis, and Rocky Mountain spotted ever diagnosed and treated?

3

When should tickborne encephalitis be suspected?

Poor land management prior to the 1920s resulted in massive de orestation in the Northeastern and upper Midwestern United States. The conservation movement and the decline in small amily arms in these parts o the country have led to the return o orest and meadow land. With re orestation has come the large scale recovery o deer and other mammals, making or conditions in which Lyme disease and other tickborne illnesses can thrive. Since it was rst described in 1977 in Lyme, Connecticut, Lyme disease has become the most common vectorborne disease in the United States. In 2013, the Centers or Disease Control and Prevention (CDC) reported over 36,000 con rmed or probable cases in the United States, with 95% o cases occurring along the eastern seaboard rom Virginia to Maine, as well as in the upper Midwest states o Minnesota and Wisconsin. Lyme disease is caused by the organism Borrelia burgdor eri, a spirochete, or corkscrew-shaped bacterium. The li e cycle o this organism includes both invertebrate (tick) and vertebrate (mammalian) hosts. The major tick vector or Lyme disease in the United States is Ixodes scapularis, with Ixodes paci cus ticks transmitting the disease in areas along the West Coast. There is no transovarian spread o B. burgdor eri; ticks are not in ected when they are hatched rom eggs. Ticks must take a blood meal during each o its li e stages (larvae, nymph, and adult), and acquire in ection by eeding on an in ected mammalian host. The vast majority o Lyme disease cases are reported rom May through August, but ticks may orage at any time the weather is warm enough or them to be active. A good rule o thumb is that i it is warm enough not to need gloves on while out o doors, it is warm enough or ticks to orage.

4

What are the clinical eatures o in ection with the newly described pathogen Babesia miyamoti?

■ RISK STRATIFICATION

Tickborne Infections Roger P. Clark, DO

Key Clinical Questions

Lyme disease may usually be managed as an outpatient. However, there may be patients with acute complications which require hospitalization. These include those with meningitis, high-degree atrioventricular (AV) block, and systemic illness with possible coin ection with Anaplasma, Ehrlichia, or Babesia species.

■ EVALUATION Lyme disease is o ten described as having three distinct phases: early localized disease, early disseminated disease, and late Lyme disease. This is a use ul ramework, but in reality Lyme may be more o a disease continuum, as there is o ten signi cant overlap o many eatures. Ea rly loca lized disea se (Ta ble 199-1). Patients with acute B. burgdor eri in ection may experience a wide variety o symptoms. In a vaccine trial in states with the highest incidence o Lyme disease, approximately 10% o those who seroconverted were asymptomatic. The most common clinical mani estation is the erythema migrans (EM) rash (Figure 199-1). This erythematous rash initially occurs at the site o the tick bite, and is round or ovoid in shape. Over time, the lesion expands, sometimes to very large proportions (>50 cm in size in extreme cases). While classically it has the bullseye appearance, most EM rashes are uni ormly erythematous, or have a darker center or slightly pronounced leading edge. It is usually painless, although sometimes it is described as pruritic. This rash was once held to be pathognomonic or Lyme disease, but it may also be seen in association with Southern tick-associated rash illness (STARI), ollowing the bite o the Amblyomma americanum, the Lone Star tick. The rash o STARI does not appear to be caused by B. burgdor eri in ection. 1604

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Data rom Nadelman RB, et al. Am J Med.1996;100:502-508; Shapiro ED. N Engl J Med. 2014;370:1724-1731; Steere AC. et al. Ann Intern Med. 1983;99:76-82, Logigian EL, et al. N Engl J Med. 1990;323:1438-1444.

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The classic bullseye rash occurs in only a minority o cases o erythema migrans. Most rashes o erythema migrans are uni ormly erythematous, or have a leading edge o slightly accentuated erythema. Many patients with erythema migrans do not recall a tick bite. Erythema migrans o ten occurs in locations where it may not be seen by the patient, such as the groins, axillae, popliteal ossa, and gluteal cle t.

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PRACTICE POINT

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Frequency 68%-80% 80%-90% 54%-80% 42%-54% 44% 28%-68% 39%-50% 5%-44% 21%-41% 4%-20% 3%-26%

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Clinical Manifestation Any systemic complaint Erythema migrans (single) Fatigue Arthralgia Myalgia Headache Fevers/chills Neck sti ness Localized lymphadenopathy Generalized lymphadenopathy Nausea/anorexia

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TABLE 199-1 Clinical Features of Early Localized Lyme Disease

With early localized in ection, patients o ten develop systemic symptoms, including atigue, malaise, arthralgias, myalgias, headaches, evers, chills, and neck sti ness. These systemic symptoms also occur in ea rly dissemina ted Lyme infection, along with additional clinical eatures which may provide clinical clues to the diagnosis—especially in those who did not develop (or notice) an erythema migrans rash.

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Figure 199 1 (A) Classic bullseye lesion o erythema migrans. (B) Lesion o erythema migrans with accentuation o erythema at the leading edge. (C and D) Erythema migrans with secondary lesions. 1605

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Patients with early disseminated Lyme disease may have multiple erythema migra ns rashes. These are thought to arise rom hematogenous spread o spirochetes. These lesions are similar in appearance to the primary lesion, but are generally smaller and do not have the central punctum which may arise as the result o the tick bite. Carditis may occur during early disseminated Lyme disease. This may be mani est as disruption o the conducting system at any level, although rst-, second-, and third-degree atrioventricular block are most commonly seen. This generally resolves within a week or so. Myocarditis and pericarditis may occur with Lyme, but are generally mild. Progressive cardiomyopathy resulting in heart ailure is generally not seen in the United States. It may rarely occur in Europe, where other Borrelia species are ound. Neurologic manifestations o Lyme disease include lymphocytic meningitis and cranial nerve palsies. Facial nerve palsy is common, and when bilateral should strongly suggest Lyme disease as the etiology. Peripheral neuropathy, mononeuritis multiplex, and radiculopathy are also seen. Very rarely, encephalomyelitis or cerebellar ataxia may be encountered. Eye involvement has been described, with conjunctivitis being the most common mani estation. Iritis, choroiditis, and panophthalmitis are rare. Mild elevations in serum aspartate aminotrans erase (AST) and alanine aminotrans erase (ALT) levels have been reported. In some cases this may be related to coin ection with other tickborne diseases such as Babesia spp. or Anaplasma. Generally, Lyme disease does not cause respiratory or gastrointestinal signs or symptoms. I these are seen, alternative diagnoses or coin ection with another organism may be suspected. Late Lyme disease occurs rom months to years a ter in ection. Patients with late Lyme disease may have no history o preceding early localized or early disseminated Lyme disease. The most common mani estation o late Lyme disease in the United States is a large joint monoarthritis or oligoarthritis. The knee is most commonly a ected, and the arthritis may be intermittent or chronic and persistent. Rarely, encephalopathy or polyneuropathy may be ound. The presence o encephalopathy should be based on ormal neuropsychological testing, showing objective evidence o cognitive changes, as well as cerebrospinal uid (CSF) antibody positivity or B. burgdor eri. In endemic areas, the diagnosis o early Lyme disease is generally made on the basis o possible tick exposure and the presence o solitary or multiple erythema migrans, with or without systemic symptoms. In order to become in ected, exposure to ticks in ected with B. burgdor eri is necessary. An in ected tick must be attached or 36 to 48 hours be ore the organism can be passed to the mammalian host. In patients with erythema migrans, Lyme serology may be negative up to 50% o the time, as a robust antibody response o ten has not yet occurred, leading to alse negative results. When a typical EM rash is not present, but Lyme disease is still suspected, serologic testing may be use ul. Care should be taken to select the most use ul and accurate test or helping diagnose Lyme disease. Many available tests are not validated and may be misleading. To help avoid misleading test results, the CDC o ers guidance on a validated procedure or testing, summarized in Figure 199-2. First, a plausible clinical suspicion and exposure must be present. A serologic enzyme immunoassay (EIA) or immuno uorescence assay (IFA) should ollow i de nitive evidence o Lyme disease is lacking (such as erythema migrans rash). A negative EIA or IFA result should lead to a reanalysis o the diagnosis. I the suspected exposure was within the past 30 days, a repeat or convalescent test could be repeated. Positive or equivocal tests should be con rmed with a western blot. For in ections suspected to have taken place within the past 30 days, a western blot IgM and IgG should be per ormed. For in ection with duration o greater than 30 days, only an IgG test should

Clinica l s us picion of lyme dis e a s e

Enzyme immunoa s s a y or Immunofluore s ce nce a s s a y

Ne ga tive te s t

P os itive or e quivoca l te s t

Cons ide r a lte rna tive dia gnos is or che ck conva le s ce nt s e rum

S e nd we s te rn blot*

*Note : if s igns or s ymptoms pre s e nt ≤ 30 d, s e nd IgM a nd IgG We s te rn Blot If s igns or s ymptoms pre s e nt >30 d, s e nd IgG We s te rn Blot only

Figure 199 2 Algorithm or Lyme disease testing.

be per ormed to avoid alse positive results. Western blot testing should not be per ormed without a preceding EIA or IFA. Other testing modalities have dubious validity and should be avoided. These include blood cultures or B. burgdor eri, assays or cell wall de cient orms o the organism, CD57 lymphocyte assays, urine antigen testing, and reverse western blot tests. Some labs o er in-house interpretation o immuoblots which are not validated. These in-house interpretations should be avoided, as most have very poor speci city. The vast majority o cases o Lyme disease can be managed as an outpatient. I clinical signs and symptoms suggest that the patient requires hospitalization, urther workup may be necessary. Testing or coin ection with Babesia, Anaplasma, and Ehrlichia should be per ormed, as well as a complete blood count, basic metabolic pro le and liver unction testing. An electrocardiogram (ECG) should be per ormed in hospitalized patients to assess or heart block and carditis. Lumbar puncture should be per ormed i meningitis or other neurologic illness is suspected. Cerebrospinal uid ndings suggestive o neurologic Lyme disease include pleocytosis with lymphocyte or monocyte predominance, elevated protein, and normal or near normal glucose levels. Cerebrospinal uid Lyme antibody testing should be per ormed. This test is very speci c, but syphilis—another spirochete in ection—may produce alse positive results; there ore, a CSF VDRL should also be ordered. Cerebrospinal uid Lyme polymerase chain reaction (PCR) is used in some research settings, but it is limited by poor positive and negative predictive values.

■ INPATIENT MANAGEMENT Treatment is based on illness duration and organ system involvement. For acute (early) Lyme disease, including erythema migrans, the ollowing oral options are available: • • • • • •

Doxycycline 100 mg po bid × 10 to 21 days, or Amoxicillin 500 mg po tid × 14 to 21 days, or Ce uroxime axetil 500 mg po bid × 14 to 21 days. Neurologic Lyme disease is treated with either: Ce triaxone 2 g once daily or 14 to 28 days, or Penicillin G 20 million units divided our times daily or 14 to 28 days.

Isolated acial nerve palsy may be treated with oral doxycycline or 2 to 4 weeks.

28 days. Occasionally, within 24 hours o initiation o treatment o Lyme disease, a patient may experience a Jarisch-Herxheimer reaction, with ever and rigors. Body aches and rash o ten occur, and rarely the patient will experience hypotension. Jarisch-Herxheimer reactions are caused by sudden treponemal lysis during the initiation o antibiotics. The patient should be advised about this possible complication prior to starting treatment. The Jarisch-Herxheimer reaction is not a drug reaction, and should not recur a ter the rst dose o antibiotics. Nonspeci c symptoms which occur weeks or months a ter treatment should not be ascribed to Jarisch-Herxheimer reactions.

■ POST-TREATMENT LYME DISEASE SYNDROME While the vast majority o patients respond to treatment with complete resolution o symptoms in a timely manner, a minority o patients continue to have persistent atigue, musculoskeletal symptoms, cognitive or memory complaints, or some combination o these. When these symptoms persist or several months, they are collectively o ten re erred to as post-treatment Lyme disease syndrome or post-Lyme disease syndrome. There is no evidence that prolonged treatment with antibiotics alters the course o these symptoms, and several high-quality studies have demonstrated that longer than standard antibiotic courses do not improve outcomes and increase the likelihood o adverse e ects.

PRACTICE POINT

•

There is no high-quality evidence to support the prolonged administration o antibiotics in patients with the so-called chronic Lyme disease. Randomized, double-blind, controlled trials in patients with persistent symptoms a ter Lyme disease have shown that longer than standard courses o antibiotics are associated with an increased risk o side e ects, with no improvement in outcomes.

■ POSTACUTE CARE For mild to moderate Lyme disease not involving the nervous system, cardiovascular system, or musculoskeletal system, the patient may ollow-up with their primary care provider. The patient should be advised that, as a ter any acute in ection, they may experience mild atigue, headache, myalgias, and arthralgias, which may persist or some time. It should be emphasized that this is not the result o chronic in ection, but simply the residual e ects o the body’s response to in ection. Patients with in ection involving speci c organ systems may require ollow-up with specialists in these areas in order to demonstrate that the results o the in ection have resolved.

C H A P T E R 1 9 9 T i c k b o r n e I n e

• Ce triaxone 2 g once daily or 14 to 28 days, or • Penicillin G 20 million units divided our times daily or 14 to

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Patients with third-degree AVblock may require temporary pacing. Patients with Lyme arthritis and without neurologic disease may be treated with either

• •

duration? Has appropriate ollow-up care been arranged? For patients being discharged with intravenous antibiotics and a peripherally inserted central catheter (PICC), has proper care o the PICC line been arranged, with dressing changes at least weekly? Has the patient been counseled regarding side e ects o medications and signs o PICC line in ection or thrombosis? Is there a plan or PICC removal? For patients receiving long-term antibiotics, has periodic monitoring o complete blood counts, creatinine, and liver enzymes been arranged, and has a provider been designated to ollow these lab tests? Has the patient been educated regarding measures to decrease or prevent tick exposures and bites, such as avoiding walking through tall grass, wearing light-colored clothing to better visualize ticks, and the using o N,N-diethyl-meta-toluamide (DEET) insect and tick repellants or acaricides such as permethrin on clothing?

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■ DISCHARGE CHECKLIST: LYME DISEASE

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BABESIA

■ EPIDEMIOLOGY Babesia species are parasites with a li e cycle involving asexual reproduction in mammals and sexual reproduction within the tick host. These organisms were discovered by Victor Babes in the 1888 and have long been important veterinary pathogens. While over 100 species have been identi ed, relatively ew seem to cause human illness. These include B. microti, B. divergens, and B. duncani ( ormerly known as WA-1). The vast majority o in ections in North America are with B. microti, while the major cause o babesiosis in Europe is B. divergens. There are scattered cases o a B. divergens-like babesiosis syndrome in Washington State, Missouri (the MO-1 strain), and Kentucky. B. duncani has been reported rom patients in Cali ornia and Washington State. Babesia is transmitted by the same tick vectors responsible or Lyme disease. In the United States, the I. scapularis tick is largely responsible or spreading Babesia to humans, who are accidental hosts. Most cases o babesiosis occur during the summer months (June through September). Babesiosis is thought to be largely unreported or under-reported, as the signs and symptoms are less apparent than with Lyme in ection. Most cases in the United States are due to B. microti, and occur in New York, New England, and the Upper Midwest. Travel to endemic areas is not always necessary or acquisition o babesiosis, as a small but signi cant proportion o Babesia in ections occur rom blood trans usion.

■ RISK STRATIFICATION Babesia in ections present with varying degrees o severity, depending on the host. In young, healthy adults, in ection may be inapparent, or mani est as a mild, sel -limited illness with ever, myalgia, and weakness, which may masquerade as a viral in ection. However, in certain populations, babesiosis can be severe and even li e threatening. Risk actors or severe babesiosis include age >50 years, splenectomy, and weakened immunity, as with HIV, transplantation, or malignancy.

■ EVALUATION Babesia in ections in humans can result in severe in ections and even mortality, but up to one-third o patients are entirely asymptomatic. Most cases in healthy adults present as a mild u-like illness, with onset within 7 to 42 days a ter being bitten by an in ected tick. Patients experience evers, chills, malaise, atigue, myalgias, and arthralgias. Headache is not uncommon, especially during ebrile episodes. Splenic or hepatic enlargement may lead to anorexia and abdominal ullness and discom ort. 1607

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Mani estations o severe disease include splenic in arction or rupture, acute respiratory ailure, and liver or renal ailure. The host immune response can lead to sepsis syndrome, including septic shock and multiorgan ailure. Acute respiratory ailure is generally due to immune-mediated noncardiac pulmonary edema. Those who are coin ected with other tickborne illnesses, such as Lyme disease or Anaplasma, tend to experience more severe in ections. Patients hospitalized with babesiosis should be evaluated or these coin ections, as treatment and potential complications would di er i these are present. In general, B. divergens and B. duncani present with more severe symptoms and complications than B. microti. With all species, higher parasitemia is associated with more severe illness and a greater risk o complications and death. The diagnosis o babesiosis is generally made on a Giemsa stain o thick and thin blood smears. Polymerase chain reaction tests are now commercially available, either alone or as part o a tickborne illness panel, which are able to detect Babesia in ection even at a very low parasitemia. PCR is more sensitive than smear. I babesiosis is still suspected a ter a negative smear, PCR testing should be pursued. PCR may also be use ul in the setting o a returning traveler to an area where malaria is endemic. The microscopic appearance o these organisms is very similar, and accurate identi cation o the organism is important in making treatment choices. Serology can be used to diagnose Babesia in ection even a ter the parasites have been cleared by the host’s immune system.

■ TREATMENT Treatment o B. microti varies depending upon the severity o illness. Those with mild or moderate in ection can be treated with atovaquone 750 mg po bid and azithromycin 500 to 600 mg po daily, both or 7 to 10 days. This is generally better tolerated than the treatment usually reserved or more severe illness: clindamycin 600 mg po tid (or 1.2 g IVbid) plus quinine 650 mg po tid. The duration or this course is also 7 to 10 days. For severe illness, or those with a parasite load o >10%, exchange trans usion should be employed. I a patient is admitted to a acility that does not o er exchange trans usion and has a high degree o parasitemia, or otherwise has severe illness, trans er to an institution that o ers this treatment should be considered. B. divergens and B. duncani are generally with oral quinine or IV quinidine, combined with clindamycin. Exchange trans usion may also be considered, especially in more severe cases or with high parasite loads. Most patients with babesiosis should be managed in conjunction with in ectious diseases consultation, especially patients who are immunocompromised, as treatment can be lengthy and complex, with close ollow-up being necessary.

PRACTICE POINT Babesiosis

• • • • •

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Consider babesiosis in patients with ebrile illness ollowing trans usion. Patients with babesiosis should be evaluated or coin ection with Lyme disease and Anaplasma, which are spread by the same tick vectors. Immunocompromised patients may have much more severe illness, especially patients who are asplenic. Patients with severe illness or parasitemia >10% should be evaluated or exchange trans usion. Check an ECG to exclude QT prolongation in patients being treated with quinine or quinidine.

smears to demonstrate parasite clearance. Monitoring the complete blood count as well as hepatic and renal unction may also be considered, especially in more serious disease.

■ DISCHARGE CHECKLIST: BABESIOSIS • Has there been a substantial reduction in the percentage o • •

• •

in ected red blood cells, to at least 90% o all cases reported in the United States. In 2012, 2389 anaplasmosis cases were reported to the Centers or Disease Control and Prevention. Fatality rates rom human granulocytic anaplasmosis (HGA) are generally in the range o 0.5% annually. Cases occur throughout the year, but most cases occur between May and September, when ticks are most actively oraging or blood meals. Human monocytic ehrlichiosis is caused by Ehrlichia chaf eensis. Most cases o human disease caused by Ehrlichia species is caused by this organism. E. chaf eensis in ections have been ound in a widespread geographic distribution, predominantly in the southeastern and central regions o the United States. This correlates to the distribution o the tick vector A. americanum (the Lone Star tick). While the majority o cases occur in the geographic areas mentioned above, the range o tick is widespread, and includes the East Coast states rom Florida to coastal Maine, so there is some overlap between the ranges o Anaplasma and Ehrlichia. However, anaplasmosis is much more common in New England than ehrlichiosis. There were 1128 cases o ehrlichiosis reported to the CDC in 2012. Case atality rates or ehrlichiosis in the United States are about 1%, slightly higher than or anaplasmosis. The seasonality o ehrlichiosis is nearly identical to that o anaplasmosis.

■ POSTACUTE CARE

■ RISK STRATIFICATION

Patients with risk actors or recurrence o babesiosis, such as HIV, rituximab therapy, and asplenia, should be monitored with serial

Patients with ehrlichiosis tend to be sicker than patients with anaplasmamosis; about hal o all symptomatic patients o ehrlichiosis

R

E

T

P

A

H

C

are hospitalized. Patients with known or suspected coin ection with other tickborne illness, those with signi cant medical comorbidities, those who are immunocompromised, or those who have signs o end-organ damage or hemodynamic instability should be hospitalized.

■ INPATIENT MANAGEMENT Doxycycline is the treatment o choice or patients o all ages in those suspected o having anaplasmosis or ehrlichiosis. The adult

9 9 T i c k b o r n e I n e c t i o n s

As with babesiosis, the spectrum o illness encountered with Anaplasma and Ehrlichia in ection ranges rom asymptomatic to multiorgan ailure and death. A ter being bitten by a tick, the mean incubation period or both organisms is about 1 week (range 5-21 days). As with Lyme disease, it appears there is some processing o the organism within the tick be ore in ection can be spread to the mammalian host. I the tick has been attached or less than 36 hours, the chance o a person being in ected by that tick is negligible. O course, in those with requent outdoor exposure, many tick bites may go unnoticed, and these occult tick bites must be considered when regarding a patient with suspected Anaplasma or Ehrlichia in ection. Following the incubation period, virtually all patients experience ever. Most have malaise, atigue, and myalgias, and a signi cant proportion have gastrointestinal complaints such as nausea, vomiting, and diarrhea. About a quarter o patients exhibit some degree o cough. Rash is ound in perhaps a quarter o HME patients, but is rare in HGA (~5%). A small percentage o patients develop severe complications. These occur more commonly with E. chaf eensis, and include acute kidney injury, disseminated intravascular coagulation, meningoencephalitis, myocarditis, and adult respiratory distress syndrome (ARDS). Patients who are immunocompromised are more likely to su er complications, and symptomatic disease occurs more o ten in the elderly. The incidence o ehrlichiosis is age related, with the highest rate o in ection reported in those in the 60 to 64 age group, while anaplasmosis is most commonly ound in the 65+ age range. The mean length o stay in those who are hospitalized is about 1 week. Common laboratory abnormalities include elevations in the liver transaminase levels (AST and ALT), low platelets, and anemia. A rise in the creatinine level is noted in roughly one-third o patients with Ehrlichia in ections, and hal o those with anaplasmosis. HGA and HME should be suspected in patients with unexplained ever and exposure to ticks in areas where these diseases are endemic, especially in the months o May through August. The presence o elevated transaminase levels, leukopenia, and thrombocytopenia are strongly suggestive, but not necessary or diagnosis. A bu y coat smear demonstrating the presence o intracytoplasmic morulae can give a very rapid presumptive diagnosis (Figure 199-3). Morulae are much more likely to be present with HGA (25%-75%) than with HME (40 years, and delay in treatment by 5 days or more are also associated with a higher risk o death.

■ EVALUATION Unlike the organisms covered earlier in this chapter, transmission o R. rickettsii via the tick salivary glands may occur a ter as ew as 6 to 10 hours o attachment. The incubation period o RMSF is 2 to 14 days, with a mean duration o 1 week. The initial presentation is generally one o nonspeci c ebrile illness, with the classic triad o ever, rash, and known tick exposure rarely being present at the initial physician visit. Fever is almost always present, and is o ten high, with temperatures exceeding 102°F (38.9°C) in two-third o cases at initial presentation. While rash is o ten lacking initially, it develops in an estimated 85% to 90% o cases. It o ten begins as a blanching, macular rash, starting at the ankles and wrists, then spreading to include the trunk, palms and soles. By this time, it is o ten petechial in nature. The presence o a rash on the palms and soles o ten alerts providers to consider RMSF as an etiology, as there are a limited number o disease states which cause rash in these areas. Headache and myalgia are usually present as well, and nausea and vomiting 1610

TABLE 199-2 Clinical Features of Rocky Mountain Spotted Fever Clinical Manifestation Fever Headache Myalgia Rash Rash on palms and soles History o a tick bite Classic triad ( ever, headache, and rash)

Frequency 81%-100% 58%-93% 72%-92% 68%-90% 49%-82% 54%-66% 32%-67%

Data rom Thornier AR, et al. Clin In ect Dis. 1998;27:1353-1360; Traeger MS, et al. Clin In ect Dis. 2015;60:1650-1658.

are ound about hal the time. Patients may also exhibit conjunctival injection (Table 199-2). Less common presentations include pneumonitis, severe abdominal pain, which may be mistaken or acute abdomen or appendicitis, hepatosplenomegaly, anorexia, diarrhea, altered mental status, ataxia, meningismus, and di use lymphadenopathy. Complications arise rom the endothelial damage caused by rickettsial invasion. These include adult respiratory distress syndrome (ARDS), cardiac arrhythmias, coagulopathy, encephalitis, skin necrosis (multiple cases o gangrene are reported in the literature), and gastrointestinal bleeding. Hemolysis may arise, especially in those with G6PD de ciency. Long-term sequelae include organ damage, neurologic de cits, or limb amputation. A high index o suspicion must be maintained or RMSF, especially in highly endemic regions. Given the organism’s widespread range, many providers may be un amiliar with the disease, and it is o ten not considered when the rash is absent or nonpetechial. The classic triad o ever, tick bite, and rash is present only one-hal to two-thirds o the time. Serology may be use ul in con rming the diagnosis, but this is o ten only retrospective, as serology is o ten negative in the rst 7 to 10 days. IgM is less speci c than IgG, and as such may represent a alse positive result. A our old rise in convalescent titers taken 2 to 4 weeks a ter initial titers is taken as strong evidence o in ection. Suggestive laboratory ndings include thrombocytopenia, anemia, elevated transaminases (AST and ALT), hyperbilirubinemia, hyponatremia, and elevated creatine kinase levels. I a lumbar puncture is per ormed, pleocytosis with monocyte predominance may be noted. The Weil-Felix test has historically been used to diagnose rickettsial in ections, but it su ers rom poor sensitivity or speci city and should be avoided.

■ INPATIENT MANAGEMENT Doxycycline is the treatment o choice or patients o all ages in those suspected o having in ection with Rocky Mountain Spotted Fever. In ectious diseases consultation should be placed in cases o li e threatening Rocky Mountain Spotted Fever, especially with a li e threatening allergy to doxycycline, or i pregnant. The adult dose o doxycycline is 100 mg po bid, generally or 7 days, and at least 3 days a ter clinical improvement and cessation o ever. For those who have a li e-threatening allergy to doxycycline or are pregnant, chloramphenicol 50 to 75 mg/kg/d given in our divided doses has been success ully used, but has a higher rate o ailure and death than doxycycline.

■ POSTACUTE CARE Appropriate ollow-up will vary depending upon the severity o illness and the presence o complications. Barring organ damage or limb ischemia, patients who are discharged prior to completion o

C H A P T E R 1 9 9 T i c k b o r n

96%-98% 89%-96% 82%-98% 59%-84% 28%-76%

Data rom Platonov AE, et al. Emerg In ect Dis. 2011;17:1816-1823; Molloy PJ, et al. Ann Intern Med. 2015;163:91-98.

o

i

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c

10 days o doxycycline, continuing or at least 3 days a ter resolution o ever? • Has appropriate ollow-up care been arranged, especially or patients with complications? • Have local and state health departments been noti ed? • Has the patient been educated regarding measures to decrease or prevent tick exposures and bites, such as avoiding walking through tall grass, wearing light-colored clothing to better visualize ticks, and the using o DEET insect and tick repellants or acaricides such as permethrin on clothing?

60% 68%-82%

e

• Has the patient been instructed to complete a minimum o 7 to

Frequency

I

SPOTTED FEVER

Clinical Manifestation Laboratory findings Thrombocytopenia Elevated transaminases Clinical signs/symptoms Fevers/chills Headache Malaise or atigue Myalgia Arthralgia

n

■ DISCHARGE CHECKLIST: ROCKY MOUNTAIN

TABLE 199-3 Features of Borrelia miyamotoi Infection

e

antibiotics should be impressed with the importance o nishing their course, and should be seen in close ollow-up by their provider.

Powa ssa n virus (POWV) and deer tick virus (DTV) are related viruses which are rare causes o encephalitis. Since Powassan virus was rst described in Powassan, Ontario in 1958, ewer than 100 cases have been reported. Powassan and deer tick viruses cause similar mani estations, and have related genetic lineages with an 84% nucleotide sequence identity. In ections occur in the same general regions where Lyme disease is ound. However, there is mounting evidence that cases in the Northeastern United States previously attributed to POWV are actually due to DTV. The enzootic cycle or POWV involves Ixodes cookei, with the usual mammalian hosts consisting o the groundhog (Marmota momax) and the striped skunk (Mephitis mephitis). The replication cycle or DTV is the same as that o Lyme disease, Anaplasma, and Babesia, involving the deer tick I. scapularis and the white- ooted mouse Peromyscus leukopus. In one case series o POWV/DTV in New York State, 12 o the 14 patients were admitted to the intensive care unit (ICU), and hal required mechanical ventilation. The all-cause mortality rate was 36%. All patients had ever, 86% had generalized weakness, and 72% complained o lethargy. About hal o the patients displayed con usion, seizures, headache, or rash. Cerebrospinal uid analysis demonstrated a modest lymphocytic pleocytosis. The CDC criteria or the diagnosis o neuroinvasive disease due to POWV/DTV requires meningitis, encephalitis, acute accid paralysis, or other acute signs o central or peripheral neurologic dys unction, as documented by a physician, in the absence o a more likely clinical explanation, along with a con rmatory laboratory test, such as isolation o virus rom CSF or blood, positive POWV/DTV IgM in CSF or serum, or a our old rise in POWV/DTV antibody titers between acute and convalescent sera. There is no speci c treatment or POWV/DTV. Some data suggest that corticosteroids may be bene cial, but urther studies are required. BORRELIA MIYAMOTOI Borrelia miyamotoi has been recently recognized as a human pathogen. First discovered in Japani in 1994, the initial human cases were described in Russia in 2011. Subsequently, a number o cases have now been ound in the United States as well. While this organism is related B. burgdor eri, the causative agent o Lyme disease, its clinical eatures more resemble that o B. recurrentis, the agent responsible or tickborne relapsing ever. B. miyamotoi usually presents as an undi erentiated ebrile illness, with headache, o ten described as severe, malaise, and prominent myalgias and arthralgias (Table 199-3). Common laboratory ndings include leukopenia, thrombocytopenia and mildly elevated

s

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TICKBORNE ENCEPHALITIS VIRUSES liver unction tests. Symptoms recur in 4% to 10% o patients. This is likely higher in those not treated with antibiotics. Currently available tests or B. miyamotoi include whole blood PCR and antibodies against GlpQ protein. Treatment is with doxycycline. Given the geographic distribution in areas where Lyme disease and Anaplasma are ound, it is very likely that some patients started empirically on doxycycline or suspected tickborne illness may have unrecognized in ection with B. miyamotoi.

SUGGESTED READINGS Centers or Disease Control and Prevention. Tickborne Diseases in the United States. 3rd ed., 2015. Available at http://www.cdc.gov/ lyme/resources/tickbornediseases.pd . Clark RP, Hu LT. Prevention o Lyme disease and other tick-borne in ections. In ect Dis Clin North Am. 2008;22:381-396. Dantas-Torres F. Rocky Mountain spotted ever. Lancet In ect Dis. 2007;7:724-732. El Khoury MY, Camargo JF, White JL, et al. Potential role o deer tick virus in Powassan encephalitis cases in Lyme disease-endemic areas o New York, U.S.A. Emerg In ect Dis. 2013;19:1926-1933. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3840892/. Horowitz HW, Aguero-Rosen eld ME, Holmgren D, et al. Lyme disease and human granulocytic anaplasmosis coin ection: impact o case de nition on coin ection rates and illness severity. Clin In ect Dis. 2013;56:93-99. Klempner MS, Baker PJ, Shapiro ED, et al. Treatment trials or postLyme disease symptoms revisited. Am J Med. 2013;126:665-669. Klempner MS, Hu LT, Evans J, et al. Two controlled trials o antibiotic treatment in patients with persistent symptoms and a history o Lyme disease. N Engl J Med. 2001;345:85-92. Molloy PJ, Tel ord SR 3rd, Chowdri HR, et al. Borrelia miyamotoi disease in the Northeastern United States. Ann Intern Med. 2015;163:91-98. Shapiro ED. Lyme disease. N Engl J Med. 2014;370:1724-1731. Wormser GP, Dattwyler RJ, Shapiro ED, et al. The clinical assessment, treatment, and prevention o Lyme disease, human granulocytic anaplasmosis, and babesiosis: clinical practice guidelines by the In ectious Diseases Society o America. Clin In ect Dis. 2006;43:10891134. http://cid.ox ordjournals.org/content/43/9/1089.long. Vannier EG, Diuk-Wasser MA, Ben Mamoun C, Krause PJ. Babesiosis. In ect Dis Clin North Am. 2015;29:357-370. 1611

200

CHAP TER

Tuberculosis Michael Gardam, MD, MSc, FRCPC Susy Hota, MD, MSc, FRCPC

Key Clinical Questions

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1

When should tuberculosis be suspected in the inpatient setting?

2

What diagnostic testing should be per ormed in patients with suspected tuberculosis?

3

What precautions are necessary or patients with possible tuberculosis? When may they be discontinued?

4

What treatment regimen should be begun or patients with newly diagnosed tuberculosis? What monitoring is appropriate in patients being treated or tuberculosis?

INTRODUCTION A global pandemic o tuberculosis (TB) that began three centuries ago continues today, although globally, rates have begun to decline or the rst time over the past ew years. According to estimates rom the World Health Organization, 9.4 million people developed active TB in 2013, and 1.5 million died. Tuberculosis remains the leading cause o death in the HIV-in ected, accounting or 26% o acquired immunode ciency syndrome (AIDS)-related deaths throughout the world. The incidence o TB is highest in Asia, A rica, Latin America, Russia, and Eastern Europe (Figure 200-1). Rates are substantially lower in developed countries, where TB is increasingly a disease o the oreign born. However, some populations in developed nations have a relatively high incidence o the disease, including homeless persons, injection drug users, incarcerated persons, and some aboriginal populations. Another group at risk in developed nations is the elderly. Rates o TB in the developed world 50 years ago were similar to rates in developing countries today. Older patients born and raised in developed nations there ore have a higher likelihood o developing active TB than younger patients, due to the risk o late reactivation o latent in ection. As TB in the developed world has become uncommon, the diagnosis is o ten overlooked, even when in retrospect it should have been airly apparent. Un ortunately, because pulmonary TB may be highly contagious, delays in diagnosis may have disastrous implications not only or the patient, but also or amily, riends, and other close contacts, including health care workers. PATHOPHYSIOLOGY Tuberculosis is caused almost exclusively by Mycobacterium tuberculosis. Rarely, it is caused by the related organism Mycobacterium bovis, acquired rom in ected cattle or contaminated milk products. M. tuberculosis is transmitted almost exclusively through the respiratory route by microscopic droplet nuclei. These particles are small enough to remain airborne or long periods o time and to be inhaled directly into the terminal alveoli, typically in the lower lung zones. Droplet nuclei are produced when a patient with pulmonary TB speaks, coughs, or sneezes. Rarely, droplet nuclei may arise rom other activities, such as irrigation o TB-in ected areas during surgery, dressing changes o draining wounds, or emptying o containers o in ectious uid. M. tuberculosis has adapted to survive within alveolar macrophages, the cells that normally would be expected to eradicate it. Within the macrophage, the organism travels to the mediastinal lymph nodes. It then disseminates throughout the body via the bloodstream, with more vascular areas receiving more organisms. Microscopic oci o live bacteria are thus deposited throughout the body, including the lung apices. Typically, 3 to 8 weeks a ter in ection, the cellular immune system responds by walling o the bacteria in granulomas. This process is paralleled by the development o a positive tuberculin skin test. Granulomas are not static structures; the organisms within them are alive, albeit dormant, and the cells orming the granuloma constantly turn over. At this stage, the in ected individual has what is re erred to as latent tuberculosis infection. Patients with latent in ection are neither ill nor in ectious to others. Roughly, 85% to 90% o otherwise healthy individuals in this state never develop symptoms throughout their li etime, despite ongoing in ection. O the 10% to 15% who do go on to develop symptoms, most do so within the rst ew years o becoming in ected. Once symptoms have developed, the patient is re erred

C H A P T E R 2 0 0 T u b e r c u l o s i s

Inc ide nc e pe r 100,0 00 0 - 24

50 - 99

300 o r mo re

25 - 49

100 - 299

No e s timate

Figure 200 1 Tuberculosis incidence in 2005, based on World Health Organization data. (Courtesy o the Stop TB Department, WHO; with permission.) to as having active tuberculosis. Although there is a predilection or disease to develop in the apices o the lungs, a large minority o patients will develop symptoms outside the lungs. Commonly involved extrapulmonary sites include regional lymph nodes, pleura, spine, bones and joints, and meninges. Patients with certain underlying medical conditions or receiving immunosuppressive therapy are at higher risk o developing active disease i in ected (Table 200-1).

PRACTICE POINT

•

About 25% to 50% o patients with extrapulmonary TB also have active pulmonary tuberculosis. Although extrapulmonary tuberculosis is not usually contagious, chest imaging is indicated in these patients to exclude concomitant contagious pulmonary disease.

CLINICAL PRESENTATION Un ortunately, the symptoms o active TB are o ten vague and nonspeci c, sometimes leading to initial misdiagnosis. It is common or a TB clinic to see patients who were initially investigated or malignancy. Patients typically report having had symptoms or weeks to months prior to being diagnosed. In some cases, symptom onset can be so gradual that patients realize the extent o their illness only a ter they have improved with treatment. Early cases can be entirely asymptomatic, having been detected on a chest radiograph per ormed or other reasons. Rarely, patients present with acute symptoms, mimicking more typical bacterial in ections, or they may develop disseminated (miliary) TB, with a rapidly progressive ebrile wasting illness, with or without pulmonary complaints. Constitutional symptoms such as weight loss, atigue, ever, night sweats, and rigors tend to be more common with pulmonary and pleural disease, together with a worsening productive cough. Massive hemoptysis was once common in the preantibiotic era, but hemoptysis is now rare, and i present, is typically minor. Constitutional symptoms may be absent in extrapulmonary TB, especially in patients with disease con ned to lymph nodes. Tuberculous

lymphadenitis is the most common orm o extrapulmonary TB. It usually presents as painless swelling o the posterior cervical or supraclavicular lymph nodes, although patients may also develop lymph node tenderness and stula ormation. Pleural tuberculosis may present with ever, dyspnea, and pleuritic chest pain i the e usion is sizable enough. Genitourinary tuberculosis may present with dysuria, urinary requency, ank pain, and hematuria, although it may also o ten be asymptomatic until hydronephrosis and severe kidney damage have occurred. Spinal tuberculosis (Pott disease) most o ten presents with back pain rom in ection o the thoracic or lumbar spine, o ten with paravertebral cold abscesses involving the psoas muscle. Tuberculous meningitis presents as subacute or

TABLE 200-1 Risk Factors for Active Tuberculosis Among Persons Who Have Been Infected with Tuberculosis Factor Recent in ection ( 55 y; weight loss > 10%; intense night sweats > 3 wk; symptoms > 2 mo; inability to work; in iltrates involving > ½ o one lung or portions o both lungs; prominent or persistent hilar lymphadenopathy; anticoccidioidal complement- ixing antibody > 1:16. ‡ Bilateral reticulo-nodular or miliary in iltrates. § Stable nodule de ined as no change in size on serial radiologic imaging or 2 y.

lymphatic channels. This pattern is known as nodular lymphangitis (Figure 202-2). Mycobacterium marinum and other pathogens may also cause a similar clinical picture (Table 202-9). Diagnosis requires ungal isolation rom tissue cultures. Itraconazole or terbina ne are used in treatment. Hot compresses may be a use ul adjunctive therapy, as heat inhibits the growth o S. schenckii.

■ PARACOCCIDIOIDOMYCOSIS Paracoccidioidomycosis is caused by Paracoccidioides brasiliensis, a dimorphic ungus endemic in South America, with most reported cases 1632

rom Brazil, Colombia, Venezuela, Ecuador, and Argentina. It mainly a ects men, and usually presents as an indolent systemic in ection over several months, leading to skin nodules, mucosal ulcerations, ulcerative lymphadenitis, and chronic pneumonia o the lower lobes. Hematogenous dissemination may lead to visceral involvement, bone disease, and involvement o the CNS. De nitive diagnosis o paracoccidioidomycosis is based on the visualization o the gemmating (budding) “ship’s wheel” yeast-like orms in biopsy specimens, as well as culture and serology. Prolonged treatment is required. Trimethoprim-sul amethoxazole or itraconazole are used in non–li e-threatening disease. Severe disease should be treated initially with amphotericin B.

C H A P T E R 2 0 2 H i s t o p l a s m o s i s , B l a s t o m y c o s i s , C o c c i d i o i d o m y c o s i s , a n d O t h e r D i

Miscellaneous: Bacillus anthracis; cowpox virus

m

Other ungi: Blastomyces dermatitidis; Histoplasma capsulatum; Cryptococcus neo ormans

o

Leishmania brasiliensis

r

Nocardia spp.

p

Francisella tularensis

h

Mycobacterium marinum

i

Sporothrix schenckii

Wheat LJ, Frei eld AG, Kleiman MB, et al. In ectious Diseases Society o America. Clinical practice guidelines or the management o patients with histoplasmosis: 2007 update by the In ectious Diseases Society o America. Clin In ect Dis. 2007;45:807-825.

c

TABLE 202-9 Differential Diagnosis of Nodular Lymphangitis

Luckett K, Dummer JS, Miller G, et al. Histoplasmosis in patients with cell-mediated immunode ciency: HIV in ection, organ transplantation, and tumor necrosis actor-α inhibition. Open Forum In ect Dis. 2015;2(1):o u116.

F

Figure 202 2 Lymphangitic spread o nodular sporotrichosis. (Reproduced,with permission, rom Wol K,Johnson RA,Suurmond D. Fitzpatrick’s Color Atlas & Synopsis o Clinical Dermatology, 5th ed. New York, NY: McGraw-Hill, 2005. Fig. 25-44.)

Kau man CA, Bustamante B, Chapman SW, Pappas PG. In ectious Diseases Society o America. Clinical practice guidelines or the management o sporotrichosis: 2007 update by the In ectious Diseases Society o America. Clin In ect Dis. 2007;45:1255-1265.

u

Galgiani JN, Ampel NM, Blair JE, et al. In ectious Diseases Society o America. Coccidioidomycosis. Clin In ect Dis. 2005;41:1217-1223.

n

Chapman SW, Dismukes WE, Proia LA, et al. Clinical practice guidelines or the management o blastomycosis: 2008 update by the In ectious Diseases Society o America. Clin In ect Dis. 2008;46:1801-1812.

g

Assi MA, Sandid MS, Baddour LM, Roberts GD, Walker RC. Systemic histoplasmosis: a 15-year retrospective institutional review o 111 patients. Medicine (Baltimore). 2007;86:162-169.

i

SUGGESTED READINGS

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CHAP TER

The Hospitalized Patient with HIV Claire E. Farel, MD, MPH Jonathan B. Parr, MD, MPH Paul E. Sax, MD

Ke y Clinical Que stio ns 1

What conditions cause symptoms in human immunode iciency virus (HIV) patients?

2

How are opportunistic in ections diagnosed and treated?

3

What nonin ectious problems are common in HIV patients?

4

When should antiretroviral therapy be started?

INTRODUCTION More than 1.2 million people are human immunode ciency virus (HIV) seropositive in the United States. As survival with HIV has increased because o antiretroviral therapy (ART), the spectrum o illness a ecting this population has expanded. Opportunistic in ections (OIs) still occur in untreated patients and patients who do not adhere to therapy. However, in patients whose HIV in ection is controlled by ART, nonin ectious problems such as metabolic syndrome, coronary artery disease, pulmonary hypertension, and malignancy are increasing in prevalence. This chapter uses a symptom-based approach to guide di erential diagnosis in HIV, and outlines the presentation, diagnosis, and treatment o common opportunistic in ections. Other aspects o HIV therapy important to the hospitalist are discussed, including medication interactions and side e ects. PATHOPHYSIOLOGY AND NATURAL HISTORY Most patients with acute HIV in ection develop symptoms between 2 and 4 weeks a ter exposure. Some patients are asymptomatic, but many report an acute ebrile illness resembling mononucleosis. Features may include rash, anorexia, mucocutaneous ulcerations, pharyngitis, lymphadenopathy, diarrhea, myalgias, and rarely meningoencephalitis. HIVantibody does not appear until 3 to 4 weeks a ter the symptoms o acute HIV syndrome develop. However, ourthgeneration HIVimmunoassays that detect both HIVantibody and p24 antigen can detect acute HIVas early as 2 weeks a ter in ection. Current guidelines recommend routine initial testing with a ourth-generation HIV immunoassay ollowed by con rmatory testing. HIV RNA (viral load) testing can detect acute in ection at as early as 5 days and should be obtained i there is concern or recent in ection, ourth-generation immunoassay testing is unavailable, or initial results are indeterminate. Clinicians should bear in mind that patients with acute HIV in ection may also have acquired other in ections, such as viral hepatitis, syphilis, or cytomegalovirus (CMV), at the time o their HIVexposure. Human immunode ciency virus depletes CD4+ lymphocytes, also known as T-helper cells, leading to OIs. In acute HIV in ection, CD4+ cells decline sharply, generally ollowed by a modest rebound, as HIVreplication is brought under partial control. Over time, viremia rises, CD4+ cells are gradually depleted, and acquired immunode ciency syndrome (AIDS) develops. The tempo or progression to AIDS has great individual variability. Illnesses such as seborrheic dermatitis, cutaneous zoster, bacterial pneumonia, and cytopenias, while not speci c to HIV, occur with increased requency in patients with waning CD4+ cells and may be a clue to undiagnosed HIV. TRIAGE/CONSULTATION Admission o the patient with CD4+ count >500 cells/mm 3, suppressed viral load, and admission or a non–HIV-related reason does not necessarily require in ectious diseases consultation. By contrast, newly diagnosed HIV, acute opportunistic in ections, undi erentiated illness in patients with more advanced HIV, or possible modi cation o ART warrant review by a specialist amiliar with HIVdisease and its management. DIAGNOSTIC APPROACH: GENERAL PRINCIPLES Along with whether the patient is currently taking ART, the most recent CD4+ cell count is critical in determining the likelihood o an

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HIV-related complication (Table 203-1). I recent CD4+ counts are unavailable, there is controversy about the use ulness o CD4+ testing in the context o acute illness, which lowers the CD4+ below the patient’s true baseline. Despite this caveat, we recommend measuring CD4+ cell count during hospital admissions, as markedly low values (eg, 200 cells/mm 3, traditional AIDS-related illnesses are vanishingly rare. Individuals with these characteristics are generally admitted or similar reasons as HIV-negative patients. However, long-term

TABLE 203-2 Laboratory Abnormalities Associated with Selected Antiretroviral Agents Drug Atazanavir Indinavir Zidovudine Teno ovir Cobicistat

Laboratory Abnormality Indirect hyperbilirubinemia Bone marrow suppression, macrocytic anemia Renal dys unction

C H A P T E R 2 0 3 T h e H o s p i t a l i z e d P a t i e n

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1.7 Rapidly improving symptoms Prior stroke or head injury within 3 mo; prior intracranial hemorrhage Major surgery in preceding 14 d Minor stroke symptoms GI bleeding in preceding 21 d Recent myocardial in arction Coma or stupor

Administration of rtPA IVaccess with two peripheral IVlines (avoid arterial or central line placement) Review eligibility or rtPA Administer 0.9 mg/kg IV(maximum 90 mg) IVas 10% o total dose by bolus, ollowed by remainder o total dose over 1 h Frequent cu blood pressure monitoring No other antithrombotic treatment or 24 h For decline in neurologic status or uncontrolled blood pressure, stop in usion, give cryoprecipitate, and reimage brain emergently Avoid urethral catheterization or 2 h See Activase (tissue plasminogen activator) package insert or complete list o contraindications and dosing. CT, computed tomography; INR, international normalized ratio; PTT, partial thromboplastin time. Modi ied, with permission, rom Fauci AS, Braunwald E, Kasper DL, et al. Harrison’s Principles of Internal Medicine, 17th ed. New York, NY: McGraw-Hill; 2008, Table 364-1. *

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include bleeding complications and angioedema. Patients whose blood pressure can be lowered sa ely with antihypertensive agents may be eligible or treatment, and the physician should assess blood pressure stability be ore starting rtPA (see below). A patient with a seizure at the time o onset o stroke may be eligible or treatment, as long as the physician is convinced that residual impairments are secondary to stroke and not a postictal phenomenon. Intravenous streptokinase or the treatment o stroke is not recommended, and ancrod, tenecteplase, reteplase, desmoteplase, urokinase, or other thrombolytic agents should not be used outside the setting o a clinical trial. American Stroke Association guidelines suggest that thrombolysis may be considered or patients between 3 and 4.5 hours a ter stroke onset, provided patients are younger than 80 years, have NIHSS ≤25, are not taking oral anticoagulants, and do not have a history o both prior stroke and diabetes. However, clinicians should bear in mind that rtPA is not FDA-approved or use in this patient population.

■ THROMBOLYSIS BEYOND 3 HOURS AFTER ONSET OF STROKE Thrombolysis in stroke is most e ective when administered as early as possible a ter the onset o symptoms. Based on the European Cooperative Acute Stroke Study (ECASS-3), there is a modest bene t o thrombolysis given between 3 and 4.5 hours a ter stroke, although this seems to be less than the bene t observed with thrombolysis between 0 to 3 hours a ter stroke onset. The eligibility criteria or treatment are similar to those or persons treated at earlier time periods. However, patients who meet any o the ollowing additional criteria should be excluded: • • • •

Patients older than 80 years Baseline NIHSS >25 Patients with a history o both stroke and diabetes All patients receiving an oral anticoagulant are excluded, regardless o their international normalized ratio (INR)

The sa ety and ef cacy o treatment with rtPA within 3 to 4.5 hours a ter stroke in patients with these exclusion criteria have not been established and require urther study. Additionally, the relative utility o rtPA in this time window compared with other methods o thrombus dissolution or removal has not been established. Patients should be in ormed that use o rtPA between 3 and 4.5 hours a ter stroke is considered o -label or investigational by the FDA.

■ ENDOVASCULAR TREATMENT Un ortunately, thrombolytic therapy or large-vessel ischemic stroke is success ul in only a minority o patients. Endovascular treatments have emerged as a success ul strategy to reduce the clot burden and restore vessel patency. In a recent large metaanalysis o high-quality clinical trials, unctional independence was markedly improved with endovascular treatment, rising rom 31% in those receiving tissue plasminogen activator (tPA) alone to 45% in those also given endovascular therapy. Rates o intracranial hemorrhage and all-cause mortality were similar between the two groups at 90 days. Subgroup analysis showed that endovascular treatment was associated with greater bene t when given a ter tPA rather than alone, that better results were achieved with stent retrievers than with other devices, and that unctional outcomes were signi cantly better in patients with angiographic imaging showing proximal arterial occlusion. Patients eligible or intravenous rtPA should receive intravenous rtPA, even i endovascular treatment is being considered. Observing patients a ter intravenous rtPA to assess or clinical response prior to endovascular therapy is not necessary to achieve bene cial outcomes and is not recommended. Patients should receive

C H A P T E R 2 0 9 T r a n s i e n t I s c h e m i c A t t a c k a n d S t

As with intravenous rtPA, reduced time rom symptom onset to reper usion with endovascular therapies is highly associated with better clinical outcomes. To ensure bene t, reper usion to TICI (Thrombolysis in Cerebral In arction) grade 2b/3 should be achieved as early as possible and within 6 hours o stroke onset. Use o salvage therapy, including intra-arterial brinolysis, may be reasonable to achieve these angiographic results i completed within 6 hours o symptom onset. When treatment is initiated beyond 6 hours rom symptom onset, the e ectiveness o endovascular therapy is uncertain or patients with acute ischemic stroke with occlusion o the ICA or proximal MCA. Additional clinical trial data are needed. In care ully selected patients with anterior circulation occlusion who have contraindications to intravenous rtPA, endovascular therapy with stent retrievers completed within 6 hours o stroke onset is reasonable. Endovascular therapy with stent retrievers may also be considered or care ully selected patients with acute ischemic stroke in whom treatment can be initiated within 6 hours o symptom onset and who have causative occlusion o the M2 or M3 portion o the MCAs, anterior cerebral arteries, vertebral arteries, basilar artery, or posterior cerebral arteries. Although bene ts are uncertain, the use o endovascular therapy with stent retrievers may be reasonable or patients with acute ischemic stroke in whom treatment can be initiated (groin puncture) within 6 hours o symptom onset and who have prestroke mRS score >1, ASPECTS 300 mg o protein

TABLE 221-12 Labor and Delivery Sample Admission Orders for Severe Pre-eclampsia

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TABLE 221-11 Lab Abnormalities in Pre-eclampsia

ALT, alanine transaminase; AST, aspartate transaminase; BUN, blood urea nitrogen; CBC, complete blood count; IM, intramuscularly; IV, intravenously; LDH, l-lactate dehydrogenase. Reprinted, with permission, rom Hypertensive disorders o pregnancy, July 1, 2008, American Family Physician. Copyright 2008, American Academy o Family Physicians. All rights reserved.

inhibitors or angiotensin II receptor blockers be ore conception together with an increase in GFR are the main reasons or a physiologic increase in proteinuria during pregnancy. Although pregnancy may accelerate the progression o nephropathy, postpartum renal unction usually returns to prepregnancy levels in most cases. In women with moderate renal insu ciency, pregnancy has 1797

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been estimated to shorten the time to end-stage renal ailure by 36 months. Hypertension occurs in 30% o women with diabetic nephropathy in the rst trimester and in 75% by the third trimester. Deteriorating renal unction and superimposed preeclampsia are responsible or the high rates o preterm delivery, low birth weight, and operative delivery. Di erentiating preeclampsia rom worsening nephropathy can be very di cult as proteinuria and worsening hypertension occur in both situations. Women with pre-existing types 1 and 2 diabetes are at increased risk o preeclampsia, operative delivery, and antenatal in ections (such as urinary tract and respiratory). These risks are urther increased i the mother has premorbid obesity as well. The rate o early pregnancy loss or congenital anomalies is increased or women with poor preconception glycemic control. Glucose is a potent teratogen and there is a linear increase in rates o congenital anomalies with rising HgbA1C levels. Late pregnancy losses are also increased in women with poor glycemic control during pregnancy. It is thought that oxidative stress resulting rom oxygen depletion caused by hyperglycemia is the underlying mechanism or these ndings. It has been shown that the overall rate o adverse pregnancy outcome is much lower in women who receive preconception counseling and are euglycemic at conception and during organogenesis. The incidence o macrosomia is increased in diabetic pregnancies. Excess etal growth is due to etal hyperinsulinemia in response to maternal hyperglycemia. Macrosomic babies (> 4000 g) are at increased risk or traumatic or surgical delivery, shoulder dystocia, and brachial plexus injury. Neonatal hypoglycemia due to etal hyperinsulinemia and neonatal hyperbilirubinemia are metabolic complications that are more common in babies born to diabetic mothers. Gestational diabetes mellitus Gestational diabetes mellitus (GDM) is de ned as glucose intolerance o variable severity that is rst detected during pregnancy. It is the leading endocrine condition in pregnancy and continues to rise in the ace o the obesity epidemic. Pregnancy is e ectively a stresstest in which the insulin-resistant hormones o pregnancy trigger overt hyperglycemia in women who have a background o previously undiagnosed insulin resistance and/or decreased pancreatic beta-cell reserve. It is usually diagnosed at the end o the second trimester via a diagnostic glucose tolerance test. Treatment needs to begin immediately as there is only a short window o opportunity to achieve euglycemia in order to minimize its impact on the etus. I the ollowing targets are not met with diet and exercise therapy alone ( asting blood glucose level or BGL < 5.3 mmol/L or 95 mg/dL and/or 1-hour postprandial BGL < 7.8 mmol/L or 140 mg/dL and/ or 2-hour postprandial BGL < 6.7 mmol/L or 120 mg/dL), insulin therapy is commenced though glyburide, or met ormin therapy may be recommended i the patient re uses insulin therapy and/or the degree o hyperglycemia is only mild. Glyburide has traditionally been the pre erred agent as it does not cross the placenta, but more recent studies have emerged regarding the sa ety and e cacy o met ormin use beyond the rst trimester. Glucose tolerance returns to normal immediately a ter delivery o the placenta and so treatment can be ceased. Women with GDM are at much greater risk o developing type 2 diabetes in the uture and so they should be tested or such on a regular basis by their primary care physicians. The use of oral hypoglycemic agents, subcutaneous insulin regimes, and insulin pumps Insulin is considered the gold standard o treatment or both preexisting and gestational diabetes. However, there has been a trend

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toward increasing use o glyburide and met ormin in recent times. There is currently no data to suggest that the use o either in the rst trimester is associated with an increase in congenital anomalies. Glyburide does not cross the placenta and can be used throughout the second and third trimesters as well. Met ormin is requently used as an ovulation induction agent in women with polycystic ovarian syndrome and or these women, continuing its use during the rst trimester has been shown to reduce miscarriage rates. Its use during the second and third trimesters had been questionable in the past given that signi cant placental trans er does take place (cord blood levels similar to maternal levels) but recent data suggests that there is no long-term deleterious e ects on the etus and it may in act reduce the risk o the o spring developing type 2 diabetes in the uture. None o the other oral hypoglycemic agents currently on the market are recommended or approved or use during pregnancy. All the insulin types available on the market are sa e or use in pregnancy. These include the newer insulin analogs, which are more rapid in onset (Humalog, Novolog) and longer in action (Lantus, Levemir) compared with the traditional recombinant human insulins (Humulin-R, Humulin-NPH). An increasing number o women o childbearing age with type 1 diabetes are using insulin pumps that provide a continuous subcutaneous in usion o insulin or glycemic control. The main caveat here is that they need to recognize potential problems such as a blockage or kink in the in usion set that can precipitate an episode o diabetic ketoacidosis more quickly in pregnant patients. Management of diabetic ketoacidosis The presentation o DKA is similar in the nonpregnant and pregnant patient, but the acidosis tends to be more pronounced at a lower serum glucose level in the pregnant patient. This is due to the combination o the accelerated starvation state o pregnancy, lower bu ering capacity due to the physiologic respiratory alkalosis o pregnancy that leads to lower serum bicarbonate levels and the increased GFR in pregnancy that leads to increased renal excretion o glucose. Treatment requires prompt recognition and maternal stabilization with rehydration, intravenous insulin therapy, and electrolyte replacement. In ections such as those o the urinary tract should be excluded. As starvation ketosis is o ten the main component o ketoacidosis, the mother needs to receive adequate dextrose (with the insulin in usion) in order to meet etal-placental glucose needs until she is eating normally. Ketone bodies and glucose cross the placenta readily and so there is high etal morbidity and mortality associated with DKA. Fetal compromise will improve once the metabolic acidosis reverses. An urgent C-section while the mother is still acidotic is not generally recommended because o high maternal risk. Management at time of labor and delivery It is recommended that an insulin plan or the time o labor and delivery be provided to all patients well be ore the expected due date so that there is no con usion between the patient and various medical and nursing caregivers. It is important to avoid maternal blood glucose levels more than 9.0 mmol/L (162 mg/dL) in the intrapartum period as this has been associated with an increased risk o neonatal hypoglycemia (which may require NICU admission), but it is also important to avoid hypoglycemia or maternal sa ety and well-being during this strenuous process. In early labor, subcutaneous insulin use should be continued while the woman is still eating but these doses will need to be reduced i oral intake is decreased. When the woman is in active labor and no longer eating, an intravenous insulin and dextrose

■ OBESITY IN PREGNANCY The prevalence o obesity worldwide has increased dramatically over the past 25 years. It a ects 26% o the population in the USA. O concern is the act that the majority o the obese population tend to be women o reproductive age, according to the WHO. Overweight and obese women are at increased risk o maternal, etal and peripartum complications. Maternal complications include gestational diabetes mellitus, gestational hypertension, preeclampsia, cesarean delivery, and postpartum weight retention. It is also well recognized that obesity is an independent risk actor or spontaneous abortion among women who conceive naturally or undergo in ertility treatment, and hence it is recommended that obese women be provided with counseling or weight reduction prior to conception. Nutrition and exercise counseling should be provided at this time as well as continuing throughout the pregnancy, in the postpartum period and subsequently be ore attempting another pregnancy. Institute o Medicine guidelines published in 2009 recommend that overweight women (BMI 25.0-29.9) should put on no more than 15 to 25 lbs and obese women (BMI >30.0) no more than 11 to 20 lbs during the entire pregnancy. Associated etal risks include an increased rate o congenital anomalies (eg, neural tube de ects), lower detection rate o etal anomalies during prenatal ultrasonography, macrosomia, prematurity, stillbirth, as well as subsequent childhood and adolescent obesity. At the time o delivery, the use o regional anesthesia is pre erred as the rate o ailed or di cult intubation is as high as one in three or obese pregnant women. It is recommended that anesthesiology consultation occurs early on during the laboring process in order to better identi y strategies to reduce the ailure rate o administering epidural or spinal anesthesia. The presence o obstructive sleep apnea may urther complicate airway and postoperative management. Obese women who require cesarean deliveries have increased rates o excessive blood loss, operative time greater than 2 hours, wound in ection and endometritis. Postoperative wound disruption is thought to be less prevalent with the use o suture closure o the subcutaneous layer. Consideration should be given

C H A P T E R 2 2 1 C o m m o n M e d i c a l P r o b l e m s i n P r e g

Management o thyroid diseases during pregnancy requires special considerations because pregnancy induces major changes in thyroid unction, and maternal thyroid disease can have adverse e ects on the pregnancy and the etus. Avoiding maternal (and etal) hypothyroidism is o major importance because o potential damage to etal neural development, an increased incidence o miscarriage, and preterm delivery. However, universal screening o pregnant women or thyroid disease is not yet supported by adequate studies, but case nding targeted to speci c groups o patients who are at increased risk is currently strongly supported. Both overt and subclinical hypothyroidism can have an adverse impact on the course o pregnancy or etal development. Overt hypothyroidism should be corrected be ore initiation o pregnancy and preconception thyroxine (T4) dosage should bring the thyroid-stimulating hormone (TSH) level < 2.6 mU/L. Women with subclinical hypothyroidism (serum TSH above the upper re erence limit but ree T4 [ T4] within the re erence limits) should also be treated with T4 replacement. This recommendation is based on observational evidence demonstrating that women su ering rom overt or subclinical hypothyroidism deliver babies with an average intelligence quotient (IQ) score seven points below the mean IQ score o children born to healthy women and women on T4 replacement. The importance o maternal thyroid hormone replacement is emphasized by the act that the etal thyroid does not develop until the second trimester o pregnancy and etal thyroid hormone production does not become optimal until mid-gestation. Maintaining a serum TSH < 3.0 mU/L is acceptable in the second and third trimesters o pregnancy. A ter delivery, the dose o T4 therapy can usually be reduced back to the preconception dosage a ter checking a repeat set o thyroid unction tests at the 6-week postpartum visit.

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■ THYROID

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With delivery o the placenta, insulin requirements rapidly decrease back to prepregnancy levels. The target range o blood glucose levels postpartum in the pre-existing diabetic is much more relaxed compared with during pregnancy, with levels between 6.0 and 10.0 mmol/L (108-180 mg/dL) all being acceptable. Breast eeding will lower blood glucose levels and having extremely tight glycemic control may increase the risk o hypoglycemia in a lactating woman. The usual postpartum insulin requirement is approximately twothirds o the prepregnancy insulin dosage. Women with type 2 diabetes may be able to discontinue insulin therapy and use diet and exercise and/or oral hypoglycemic agents in the postpartum period. The two oral hypoglycemic agents that have been documented to be sa e in breast eeding are glyburide and met ormin. The ormer does not enter breast milk at all and in ant exposure to the latter has been estimated to be only approximately 0.5% o the maternal dose. ACE-inhibitors or angiotensin II receptor blockers can also be recommenced in lactating women, though it is recommended that a preterm in ant not be exposed to it until he has reached an age equivalent to ull term.

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Management in the immediate postpartum period

to using a higher dose o preoperative antibiotics or surgical prophylaxis. Obesity is also an additional risk actor or thromboembolic events and hence the routine use o pneumatic compression devices ollowing cesarean deliveries is recommended. Prophylactic anticoagulation or 2 weeks is also recommended in obese individuals with additional risk- actors. Obese women are less likely to initiate and sustain breast eeding. The number o obese reproductive-aged women undergoing bariatric surgery is increasing. The two most common procedures currently per ormed are gastric bypass and sleeve gastrectomy (about 50% each). It is generally recommended that pregnancy be delayed or 12 to 18 months postoperatively. With gastric bypass patients, there is an increased risk o ailure in absorption o medications (eg, oral contraceptive pill, extended release ormulations such as met ormin). Care should be taken to monitor and supplement these patients with micronutrients such as iron, olate, vitamin B12, calcium and vitamin D. Oral glucose tolerance tests may not be well tolerated due to the dumping syndrome and so routine blood glucose monitoring is o ten recommended in these patients.

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in usion should be commenced to keep the blood glucose levels in the desired range o 4.0 to 8.0 mmol/L (72-144 mg/dL). For patients with active proli erative retinopathy, using the Valsalva maneuver repeatedly in the second stage o labor is a concern as there is an increased risk o retinal hemorrhage.

Hyperthyroidism I a suppressed TSH is detected during pregnancy, hyperthyroidism must be distinguished rom normal physiology (gestational thyrotoxicosis) and hyperemesis gravidarum because o the potential adverse e ects on the mother and etus. Hyperthyroidism in pregnancy is not rare; estimated prevalence is 0.1% to 0.4% with Graves disease accounting or 85% o cases and toxic solitary or multiple nodules plus thyroiditis accounting or most o the rest. Hydatidi orm molar disease is a very uncommon cause these days due to the advent o dating ultrasounds. 1799

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Gestational thyrotoxicosis presents in the mid- to late rst trimester, o ten with hyperemesis. Classical hyperthyroid symptoms are absent or minimal apart rom weight loss, which is o ten the result o malnutrition secondary to vomiting. The suppression in TSH is mediated by rising human chorionic gonadotropin (hCG) levels and there ore it will usually sel -resolve by mid-gestation at the latest. Approximately 50% o women su ering rom hyperemesis have a subnormal TSH and elevated T4 level. In this setting, the assessment o ree triiodothyronine ( T3) level and thyroid-stimulating immunoglobulin (TSI) level are help ul as 90% o hyperemesis cases have normal T3 and most cases o Graves disease will be TSI positive. I Graves disease or hyper unctioning nodules are diagnosed, propylthiouracil is pre erred to methimazole because o the association with congenital abnormalities with the latter medication. Therapy should be adjusted to maintain maternal T4 in the upper nonpregnant re erence interval. Though rare, the possibility o neonatal Graves disease needs to be entertained i the maternal TSI levels are high in the third trimester. Women with well-controlled Graves disease during pregnancy should be warned about the possibility o postpartum f are-up, which usually occurs between 6-weeks and 6-months postpartum. It is not recommended that radioactive iodine therapy be used during pregnancy and lactation. Postpartum thyroiditis Postpartum thyroiditis may occur in up to 10% o all pregnancies, usually between 6 weeks and 6 months a ter delivery, but it can occur up to 1 year later (see Chapter 222 [Postpartum Consultation or Common Complaints]). A hypothyroid phase o ten ollows the hyperthyroid phase and is occasionally permanent. Monitoring is necessary, as women may be hypothyroid at the time o any subsequent pregnancy.

■ PARATHYROID Hypercalcemia Primary hyperparathyroidism is usually diagnosed during pregnancy through routine blood testing ollowing prolonged or extremely severe hyperemesis gravidarum or else the serendipitous nding o nephrocalcinosis, renal calculi, or excessive calci cation o the placenta during etal ultrasonography. It may requently be part o the multiple endocrine neoplasia (MEN-1 or MEN-2a) syndrome. Urinary calcium excretion is typically not used as part o the diagnostic evaluation as it is increased in normal pregnancy. Symptomatic hyperparathyroidism is best treated by minimally invasive surgical removal o the parathyroid adenoma during the second trimester, a ter embryogenesis is complete and be ore such time that premature labor may be stimulated. In skilled hands, the procedure takes no more than 30 minutes. Surgery can also be o ered in late pregnancy (a ter 35 weeks’ gestation) i the patient becomes pro oundly symptomatic, as the neonatal outcome is much improved with surgery. This is due to the reduced risk o stillbirth, intrauterine growth restriction (IUGR), premature labor, and especially neonatal hypocalcemictetany, which can requently cause prolonged neonatal intensive care unit admissions especially i etal parathyroid suppression takes a long time to recover. Hypocalcemia Hypoparathyroidism is very rare in pregnancy and is usually part o the autoimmune polyglandular syndrome, which would requently be associated with mucocutaneous candidiasis and adrenal insu ciency. Maintenance o normocalcemia involves substantial oral supplementation with calcium and activated vitamin D (calcitriol). The doses o supplementation usually have to be increased, particularly in the third trimester, as there is high etal uptake o calcium into the skeleton. 1800

TABLE 221-13 Causes of Hypopituitarism in the Pregnant Patient Pre-existing be ore Pregnancy Pituitary adenoma Vasculitis In iltrative disorders (hemochromatosis, sarcoidosis, amyloidosis) Hypothalamic tumors (craniopharyngiomas, germinoma, meningioma, glioma) Eosinophilic granuloma (histiocytosis X) Pituitary apoplexy Prior surgical or radiotherapy treatment During Pregnancy or Postpartum Lymphocytic hypophysitis/in undibulohypophysitis Sheehan syndrome (peripartum necrosis)

■ PITUITARY Pituitary insufficiency The di erential diagnosis o pituitary insu ciency in the pregnant patient is diverse and is listed in Table 221-13. The management o the pregnant woman with pre-existing pituitary insu ciency centers on adequate hormonal replacement. In general, thyroid hormone and cortisol requirements increase throughout pregnancy due to increased hepatic production o thyroxine-binding globulin (TBG) and cortisol-binding globulin (CBG). It is vital that T4 rather than TSH level is monitored as the latter will always be low in patients with hypopituitarism. Hydrocortisone is generally the pre erred glucocorticoid replacement therapy o choice as there is minimal transplacental passage to the etus. Mineralocorticoid replacement is not required in pituitary insu ciency as the renin-angiotensin-aldosterone axis is intact. Regular obstetrical ollow-up with serial ultrasounds to detect IUGR is recommended. Stress doses o glucocorticoids must be given at the time o labor and delivery; please re er to the section on Primary Adrenal Insu ciency or recommended doses. See Chapter 222: Postpartum Consultation or Common Complaints on lymphocytic hypophysitis and Sheehan syndrome.

■ PROLACTINOMAS It is uncommon or pregnancy to occur in women with untreated prolactinomas because hyperprolactinemia is associated with in ertility. However, the ability o dopamine agonists to reduce prolactin levels to the normal range restores ovulation in about 90% o patients, many o whom are then able to achieve pregnancy. Rising estrogen levels during pregnancy have a stimulatory e ect on prolactin secretion that can cause the growth o the lesion. The risk is much higher or macroadenomas compared with microadenomas. For this reason, dopamine agonists are always discontinued once pregnancy is con rmed in someone with a microadenoma. With macroadenomas, dopamine agonists are requently continued throughout pregnancy in order to prevent tumor growth. Numerous studies have shown that there are no adverse e ects on the etus with the use o bromocriptine. There is much less data on cabergoline, but it is thought to be sa e as well, though it is not avored in any case due to its longer hal -li e. It is recommended that prepregnancy baseline visual eld testing and MRI imaging o the pituitary be done or women with macroadenoma and that they be reviewed on a regular basis (every 4-6 weeks) throughout gestation or evidence o tumor expansion.

The most common cause is immune-mediated destruction o the adrenal cortex (Addison disease). This diagnosis should always be entertained in patients who have irretractable lethargy, nausea, and vomiting that is out o keeping with normal symptoms o pregnancy. A normal pregnancy outcome should be expected as long as the patient takes the appropriate dosages o glucocorticoids and mineralocorticoids; these doses o ten need to be increased slightly throughout pregnancy as rising progesterone levels act as antagonists to the glucocorticoid and mineralocorticoid receptors. Hydrocortisone and prednisone are the pre erred glucocorticoid replacement agents as their placental passage to the etus is much lower compared with dexamethasone or betamethasone. Stress doses must always be administered in times o severe hyperemesis or physical stress as well as at the time o labor and delivery; please re er to Table 221-14 or a suggested protocol o the latter. Pheochromocytoma This condition can have pro ound e ects on both mother and etus and so it is important that it be considered as part o the di erential

TABLE 221-14 Stress Dose Steroids During Surgery or Delivery 1. Hydrocortisone 100 mg IVon call to operating room or at onset o labor 2. Hydrocortisone 100 mg IVevery 8 h over course o surgery or labor and delivery 3. Hydrocortisone 50 mg IVevery 8 h day 1 postoperative or postpartum 4. Hydrocortisone 25 mg orally every 8 h day 2 postoperative or postpartum 5. Usual preadmission doses o hydrocortisone orally rom day 3 postoperative or postpartum

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The development o new-onset diabetes insipidus in the third trimester is usually due to increased vasopressinase activity either due to increased placental production or decreased hepatic vasopressinase metabolism due to liver damage rom various causes including preeclampsia, acute atty liver o pregnancy, or HELLP, syndrome. This phenomenon is called transient vasopressin-resistant diabetes insipidus (DI) o pregnancy. Pre-existing central diabetes insipidus o ten worsens during pregnancy due to the increased clearance o endogenous vasopressin by increasing levels o vasopressinase. Subclinical central DI can also be unmasked or the rst time during pregnancy due to this mechanism. DDAVP is the treatment o choice or both central DI and transient vasopressin-resistant DI o pregnancy as it is not degraded by vasopressinase. Thiazide diuretics, which are used or the treatment o nephrogenic diabetes insipidus, are sa e to be continued during pregnancy. Transient vasopressin-resistant DI o pregnancy tends to resolve a ew days to weeks a ter delivery.

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diagnosis or hypertension in the pregnant woman, particularly in the rst hal o pregnancy. Fasting plasma metanephrine levels are the most sensitive and speci c diagnostic test, though it should be noted that the levels are slightly increased in pregnancy. Falsely elevated levels can be caused by pharmacologic agents such as tricyclic antidepressants, labetalol, and methyldopa. Anatomic localization is required or de nitive treatment once a biochemical diagnosis has been made. In pregnancy, the modality o choice to achieve this is MRI. Nuclear scanning with metaiodobenzylguanidine (MIBG) is contraindicated in pregnancy. Medical therapy in the orm o alpha-blockade should be initiated once a biochemical diagnosis is made; and the patient should be counseled that the bene ts o alpha-blockade in pregnancy ar outweigh any potential unknown e ects. Beta-blockade is then instituted a ter alpha-blockade is achieved to avoid tachyarrhythmias; the dose should be titrated to achieve a maternal heart rate o 80 to 100 beats/min. Surgery, in the orm o laparoscopic adrenalectomy, can be considered once adequate medical therapy and localization o the lesion have been achieved. I the lesion is diagnosed during the rst two trimesters, the best time to operate is during the second trimester, and i the lesion is diagnosed during the third trimester, surgery should be delayed until delivery though the timing o this will need to be brought orward i the mother remains symptomatic despite the medical blockade. An elective C-section is the delivery method o choice as the process o labor exacerbates the catecholamine surges.

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There is no role or measuring prolactin levels throughout pregnancy as the levels increase in any case. In the postpartum period, lactation has not been shown to increase the size o adenomas and is strongly encouraged.

Primary hyperaldosteronism This condition is requently unmasked in the postpartum period as the high progesterone levels during pregnancy antagonize the action o mineralocorticoids on their own receptors. Hypertension with hypokalemia is the classic presentation, though o ten the potassium level may be normal. Both renin and aldosterone levels are increased during pregnancy. There ore a suppressed renin level may be use ul in diagnosing this condition during pregnancy. Medications that suppress renin levels such as β-blockers and calcium channel blockers need to be discontinued or at least 2 weeks be ore ormal testing o renin and aldosterone levels. It is recommended that spironolactone not be used in pregnancy due to its antiandrogenic e ects; there is a theoretical risk that eminization o a male etus may occur. Calcium channel blockers are regarded to be the most e ective antihypertensive agent, as they have some e ect in reducing aldosterone synthesis and release. I the hypertension and/or hypokalemia cannot be controlled medically, laparoscopic removal o the a ected adrenal gland during the second trimester may be warranted. DEPRESSION Depressive disorders a ect at least 12% o women at some time in their lives. In the United States, depression is the leading cause o nonobstetric hospitalization among women age 18 to 44 years. The peak period or onset o depression occurs during the childbearing years and its impact extends to the o spring and the amilies involved. Un ortunately, perinatal depression remains underdiagnosed and undertreated in ob-gyn and primary care settings. Furthermore, the diagnosis o depression in pregnant women can be challenging because there is great overlap between the diagnostic symptoms o depression and the symptoms o normal pregnancy. A systematic review ound prevalence rates o depression that vary rom trimester to trimester: 7.4% in the rst, 12.8% in the second, and 12% in the third trimester. Risk actors or depression in 1801

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pregnancy include a previous depressive episode, recent negative li e events, adolescence, unmarried status, nancial disadvantage, A rican American or Hispanic ethnicity, and poor social support. Untreated depression can lead to harm ul prenatal health behaviors such as poor nutrition, poor prenatal medical care, smoking, alcohol, and other substance use. The etus o untreated depressed women may demonstrate abnormal neurobehavioral responses such as altered heart rate reactivity. Obstetric complications associated with depression include preeclampsia, preterm delivery, low birth weight, miscarriage, small- or-gestational age babies, low Apgar scores, neonatal complications, and high neonatal cortisol levels at birth. Exposure to higher cortisol levels is thought to be the mechanism o the e ect on later childhood development that may include language and cognitive impairment, sleep problems, impulsivity, attention de cit disorders, behavioral dyscontrol, and psychopathology.

■ ANTIDEPRESSANT USE AND PREGNANCY How can depressive symptoms be treated during pregnancy? Depression in nonpregnant patients is mostly treated with selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRI). Up to 9% o women have taken an antidepressant at some point during gestation, given that at least onehal o pregnancies are unplanned. Most o these exposures will be to one o the newer antidepressant medications. The odds ratio o 1.7 or spontaneous miscarriage with SSRI exposure, and reports o a 1.45 relative risk are within the range o the normal population. Most meta-analyses report that newer antidepressants do not increase the risk o mal ormation rates above the 1% to 3% population baseline risk. The teratogenicity data rom Denmark reports a 1.34 increased relative risk, but it does not control or underlying maternal psychiatric disorders. Small increased risk in omphalocele, craniosynostosis, and anencephaly with all SSRIs, and right ventricular outf ow tract obstruction with paroxetine have been ound in some other studies, but these ndings were not replicated in other studies. Nevertheless, the Food and Drug Administration issued a public health advisory in 2005 regarding paroxetine and the FDA pregnancy category was changed rom C to D. Neonatal adaptation symptoms with maternal SSRI exposure have been reported. The syndrome described includes transient and usually mild jitteriness, poor muscle tone, weak or absent cry, respiratory distress, hypoglycemia, low Apgar scores, and possible seizures. The drugs with the highest association with the neonatal adaptations syndrome include paroxetine, f uoxetine, and venlaaxine, with one study reporting on citalopram as well. Long-term sequelae have not been systematically studied and an accurate blinded in ant assessment as well as a neonatal behavioral symptom scale should be help ul in examining this syndrome more accurately. A case control study published in 2006 showed an increased risk o persistent pulmonary hypertension o the newborn (PPHN) rom a baseline o 1 to 2 per 1000, to 6 to 12 per 1000 or in ants exposed to SSRI a ter 20 weeks o gestation. The authors o the study suggest that SSRIs may promote pulmonary artery constriction a ter birth by inhibiting nitric oxide or by a direct e ect on pulmonary smooth muscle cells. These theories have been challenged, and urthermore, SSRI use be ore week 20 seemed to be a somewhat protective actor against PPHN, so it is di cult to advise patients about the absolute risk. Other psychotropic medications and pregnancy Benzodiazepines are used during pregnancy or management o anxiety or insomnia. Meta-analyses have identi ed a small increased risk o oral cle t with in utero exposure, though a case-control study ailed to con rm this teratogenic risk. Pyloric stenosis and alimentary

1802

tract atresias have also been reported, as well as low birth weight and f oppy in ant syndrome. I benzodiazepines need to be used, consider delaying treatment until a ter oral cle t closure and choose medications with shorter hal -lives at the lowest possible dose. Mood stabilizers are the most widely used medications or management o mood instability (mania, depression, and psychosis in bipolar patients) and include lithium and the antiepileptic medications. The main concern with rst trimester exposure to lithium is an increased risk (0.1%) in Ebstein anomaly, which has a risk o 0.05% in the unexposed population. Lithium remains one o the pre erred treatments or bipolar disorder and this increased risk needs to be weighed against the risk o a mood decompensation. Stable serum levels may require increase in dosages as the pregnancy progresses due to the normal changes in blood volume in pregnancy. Care ul monitoring o dosage and lithium level at delivery is recommended to avoid toxicity. Valproate has an increased risk o neural tube de ects o 5% to 9% with rst trimester exposure and a etal valproate syndrome that includes cardiovascular abnormalities and developmental delays, and cranio acial abnormalities have been described. There is newer in ormation that exposure to valproate later in gestation may be associated with neurobehavioral changes as well. Toxicity at birth with valproate may include decreased brinogen levels, liver toxicity, hypoglycemia, deceleration in heart rate, abnormal muscle tone, and lower IQ. Women o reproductive age who are planning to have children should be switched rom valproate to another agent prior to pregnancy so that the disease can be controlled by an alternative agent be ore gestation. Exposure to carbamazepine in the rst trimester carries an increased risk o cranio acial abnormalities, ngernail hypoplasia, growth restriction, and a risk o neural tube de ect o 0.5% to 1%. Lamotrigene is associated with an increased risk o congenital mal ormations similar to the general population (2%-3%). Some studies have suggested an increased risk o cle t palate de ormity and it is worth noting that in ants with antigen characteristics that di er rom the mother may be at increased risk or skin rash and liver toxicity. Haloperidol is the most commonly used antipsychotic in pregnancy because several studies have not ound increased risks o congenital mal ormations. Chlorpromazine has a poor side-e ect pro le in pregnancy due to orthostasis and sedation and has an increased risk o mal ormations o 2.4% and so should generally be avoided. Newer antipsychotics are better tolerated than the above mentioned medications, but the data regarding sa ety with these is limited. Some studies have shown no increased risk o major mal ormations with olanzapine, risperidone, quetiapine, and clozapin but have ound lower birth weight. Side e ects o these medications can also be problematic in pregnancy, particularly weight gain and glucose intolerance. Postpartum blues, depression, and psychosis Between 15% and 85% o normal postpartum women may experience the blues (postpartum blues), which present within the rst 10 days a ter giving birth with a peak incidence at the th day. It can be di cult to distinguish rom a true depressive disorder given that symptoms include mood swings, mild elation, irritability, tear ulness, atigue, and con usion. Women who experienced postpartum blues may have a history o premenstrual dysphoria and depression. No treatment is required other than improved sleep and support, but it can be a risk actor or postpartum depression. The DSM IV classi es postpartum depression as a major depressive disorder with a speci er o postpartum onset within 1 month a ter childbirth. Screening with a speci c tool such as the Edinburgh Postnatal Depression Scale (EPDS) is important since it emphasizes

Antipsychotics and breastfeeding Studies o the sa ety o both rst- and second-generation antipsychotics are quantitatively insu cient to make speci c recommendations regarding breast eeding. Risperidone and chlorpromazine have the lowest degree o excretion in breast milk and there is only one case report o drowsiness with chlorpromazine. One antipsychotic, clozapine, is considered contraindicated with breast eeding due to high in ant-relative dosage and reported adverse e ects. The available data suggests that the amount o medications (anxiolytics) to which newborns are exposed is not very high; it is important to note that neonates metabolize these medications more slowly than adults and accumulation may occur, causing in ant sedation, nausea, and poor eeding. There ore, long-acting medications are not recommended, and the lowest possible dose o a short-acting benzodiazepine should be used i these medications are needed while breast eeding. NEUROLOGY

C H A P T E R 2 2 1 C o m m o n M e d i c a l P r o b l e m s i n P r e g n c

Seizure disorders complicate approximately 1% o all pregnancies, and up to 10% o epileptic women will present or the rst time during pregnancy. Not all seizures result rom epilepsy. Both patients with and without known seizure disorders may have seizures as a consequence o preeclampsia or eclampsia, so investigation or preeclampsia is necessary or all third-trimester seizures. Although most antiepileptic drugs have teratogenicity o various degrees, epileptic women have an increased risk o etal mal ormations even without their administration. The maternal and etal risk o uncontrolled seizures resulting in hypoxemia and acidosis must be part o any risk-bene t assessment o withdrawing e ective treatment. I a patient has been seizure ree or greater than a year, holding treatment rst trimester in consultation with a neurologist could be considered. The dosage o antiepileptic medications may be inf uenced by the increased volume o distribution and by increases in hepatic and renal clearance. Valproate and carbamazepine are pre erred in breast eeding women, given the low degree o excretion in breast milk and limited reported adverse e ects in in ants. Lamotrigene has its own particular set o concerns. Even though only 60% o the drug is trans erred to the breast milk, in ants present with higher-than-expected drug levels when breast ed.

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■ EPILEPSY

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intracerebral hemorrhage, which may be related to thrombosis and/or preeclampsia.

GASTROINTESTINAL DISEASE

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clinical domains o depression and may help di erentiate rom normal postpartum ndings. Risk actors or postpartum depression include depression during or prior to the pregnancy, previous premenstrual dysphoria, stress ul li e events during the pregnancy, poor social support, marital conf ict, low income, immigrant status, and young maternal age. It is thought that the etiology may be related to hormonal f uctuations, either as a direct inf uence in mood or due to their a ect on sleep patterns in the postpartum period. Postpartum psychosis is a true psychiatric emergency that occurs in 1 to 2 per 1000 births. The onset usually occurs within the rst 4 weeks a ter delivery, although mani estations o the clinical picture can be present in the rst 3 days postpartum. The cognitive disorganization that occurs with postpartum psychosis may result in a mother’s neglect o her in ant’s needs and unsa e practices. It is highly associated with bipolar disorder and most o the time requires inpatient psychiatric hospitalization or rapid stabilization and decreased risk o suicide or in anticide. Patients present with acute con usion, delusions, and grossly disorganized behavior. The use o antidepressants during lactation or treatment o PPD or other psychiatric disorders such as obsessive-compulsive disorder and panic disorder is an important clinical issue. The evidence on the e ects o antidepressants during breast eeding consists o small sample studies and case reports. It is important to take into account the amount o medication present in the breast milk, the reported adverse events, and the in ant serum level o the drug to discuss recommendations with patients. Pooled analyses indicate that sertraline and paroxetine tend to have undetectable in ant serum drug levels. Fluoxetine and citalopram were more likely to result in elevated breast milk levels. O the tricyclic antidepressants, nortriptyline and imipramine have the largest serum level data showing levels that are not detectable. Doxepin, on the other hand, has been associated with sedation and respiratory depression and is considered contraindicated in breast eeding women.

■ ABDOMINAL PAIN Gastroesophageal ref ux disease occurs due to delayed gastric emptying and decreased gastroesophageal sphincter tone rom progesterone e ects on smooth muscle. Constipation is also common and related to the e ects o progesterone upon the smooth muscle o the bowel. The di erential o abdominal pain is broad and includes contractions, pain rom adhesions inter ering with expansion o the uterus into the abdomen, urinary retention, degenerating broid, ectopic pregnancy, ovarian torsion, stress on the round ligaments as the uterus expands, rupture o an ovarian cyst, and bleeding into a corpus luteal cyst. Late in pregnancy, uterine contractions, abruption placentae, pelvic arthropathy, and rarely rectus hematoma may occur. Vomiting, pyelonephritis, appendicitis, cholecystitis, and rarely volvulus o the large bowel may also be seen during pregnancy.

■ CHOLELITHIASIS Pregnancy is a risk actor or the development o cholesterol gallstones and biliary sludge. Higher estrogen levels increase biliary cholesterol secretion and higher progesterone levels decrease gallbladder smooth muscle motility. Preexisting gallstones are more likely to cause symptoms.

■ HEADACHES

■ BUDD-CHIARI SYNDROME

In general, pregnancy does not have a consistent impact on the requency or severity o migraine headaches and the onset o migraines may begin during pregnancy. Migraine that presents or the rst time a ter 20 weeks’ gestation should prompt an investigation or preeclampsia. Pseudotumorcerebri is an unusual cause o headache that is more requently seen in pregnant women. The undoscopic examination will reveal papilledema but otherwise the neurologic examination will be normal. Increased intracranial pressure on the optic nerve may cause progressive visual loss. The postpartum period (de ned as 6 weeks a ter delivery) but not pregnancy is associated with an increased risk o stroke and

Pregnancy-associated hypercoagulability is also a risk actor or hepatic vein thrombosis or the Budd-Chiari syndrome. Typically, patients suddenly develop abdominal pain and ascites a ter delivery.

■ JAUNDICE Common causes o jaundice during pregnancy include cholestasis rom raised estrogen levels, acute atty liver o pregnancy, disseminated intravascular coagulopathy, severe preeclampsia, hyperemesis, and severe septicemia in late pregnancy. Drug e ects (chlorpromazine, tetracycline, steroids), chronic liver disease, gall stones, and chronic hemolysis should also be considered. 1803

■ LIVER DISEASE Some o the physiologic changes o pregnancy can simulate laboratory abnormalities seen with liver disease. For example, serum albumin concentrations typically decrease rom a mean o 4.2 g/dL in nonpregnant women without liver disease to 3.1 g/dL at the end o gestation due to an increase in plasma volume. Due to leakage o placental alkaline phosphatase into the maternal blood during the th month, typically serum alkaline phosphatase levels rise. Hepatosplenomegaly should not be ound in the normal pregnancy and bilirubin, AST, ALT, and 5’nucleotidas, and γ-glutamyl levels should be normal. Telangiectasis o the chest, back, and ace and palmar erythema may occur in up to 60% o normal pregnant women but should disappear a ter delivery. Acute atty liver o pregnancy (AFLP) can lead to jaundice, liver ailure, and death.

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Pregnancy associated changes

Diagnosis The week o gestation may provide an important clue to the diagnosis. Liver diseases speci cally associated with pregnancy occur at certain times. In the rst trimester, nausea and vomiting with jaundice is consistent with hyperemesis gravidarum and AFLP has not been reported to occur during this time. Cholestasis o pregnancy typically presents at 30 weeks, usually with generalized pruritis, malaise, and atigue due to symptoms being worse at night. Jaundice may develop in one-third to one-hal o patients a ter the onset o pruritis. In 5% to 10% o pregnancies, liver diseases may develop with preeclampsia and eclampsia in the third trimester. In approximately 1 in 13,000 pregnancies, AFLP occurs in the third trimester. The pattern o serum liver enzyme abnormalities may be helpul in establishing the diagnosis. The jaundice o cholestasis o pregnancy is usually not severe, less than 6 mg/dL along with elevated alkaline phosphatase levels three to our times the upper limit o normal in pregnancy and elevated serum bile acids. With preeclampsia and eclampsia, the liver injury is due to hepatocellular injury or ischemia so aminotrans erase levels are more elevated than alkaline phosphatase or bilirubin. When patients develop abdominal pain, hypotension, ever, leukocytosis, nausea, and vomiting with abnormal liver tests in the third trimester, hepatic in arction, subcapsular hematoma, and hepatic rupture are rare complications o preeclampsia and eclampsia. AFLP is a disease o acute hepatocyte ailure so laboratory tests may be initially unimpressively abnormal. I the serum transaminases rise to more than 10 times the upper limit o normal, alternative diagnoses should be considered. The prothrombin time and rising bilirubin are the most reliable indicators o hepatic ailure. Treatment For patients with AFLP, supportive care and early delivery are critical due to the high etal and maternal mortality. I hepatic ailure is present, patients should be re erred to a transplant unit early in the course. Likewise, the pre erred treatment o patients with severe preeclampsia-related liver diseases is delivery. Effect of chronic liver disease on pregnancy Pregnancy does not alter the progression o chronic liver disease, but the outcome o the pregnancy may be inf uenced by the patient’s overall health, resulting in a higher incidence o miscarriage and prematurity. HEMATOLOGIC CONDITIONS

■ SICKLE CELL DISEASE Rates o severe preeclampsia, chest and urinary in ections, and biliary disease are higher in pregnant patients with sickle cell disease. 1804

Even in high-risk perinatal clinics, the perinatal mortality rate and maternal mortality rate is increased. VENOUS THROMBOEMBOLISM IN PREGNANCY

■ INCIDENCE There is a ve- old increase in the incidence o venous thromboembolism in pregnancy that occurs at an incidence o 0.5 to 3 per 1000 pregnancies. VTE continues to be the leading nonobstetric cause o maternal death in the developed world. Thromboembolic events are evenly distributed throughout the three trimesters and the postpartum period, although more recent studies suggest a slightly higher incidence in the rst trimester. In addition, because the postpartum period is by de nition shorter (6 weeks, as compared to 12 weeks in a trimester), the day-to-day risk o VTE in the postpartum period is higher. The incidence o atal pulmonary embolism is also higher in the postpartum period. Pregnancy is a hypercoagulable state, characterized by an increase in levels o clotting actors, decrease in anticoagulant activity (lower levels o protein S and increased activated protein C resistance), and decreased brinolytic activity. In addition, stasis induced by venous compression by the gravid uterus and hormonal inf uence on vasculature urther adds to the coagulant risk. Risk actors that may contribute to the development o VTE in pregnancy include prolonged bed rest, cesarean section, obesity, parity >3, underlying thrombophilia, prior VTE, or preeclampsia. The genetic predisposition to VTE may be identi ed by a positive amily history in those patients or whom pregnancy is an additional risk actor. Diagnosis Clinical eatures o deep vein thrombosis (DVT) include pain and swelling in the a ected leg, but it is important to remember that lower-extremity edema in pregnancy is common and is o ten asymmetric. Anatomy o the pelvic vasculature is such that the right iliac artery crosses over the le t iliac vein. With the cardiovascular changes o pregnancy, there is compression o the le t iliac vein by the right iliac artery, resulting in asymmetric lower-extremity edema (le t greater than right) and the nding that the vast majority o DVTs occur in the le t leg. Symptoms o pulmonary embolism include dyspnea, chest pain that may be pleuritic, syncope, hemoptysis, and apprehension. Shortness o breath is a very common complaint in pregnancy, but tachypnea is always an abnormal nding. The diagnosis o PE should be considered in a dyspneic pregnant woman who is tachycardic and tachypneic. Clinical diagnosis o DVT and PE in pregnancy is unreliable. Compression o pelvic veins by the gravid uterus can make interpretation o results di cult. In addition, isolated iliac vein thrombosis may not be picked up by routine methods o detection. D-dimers are known to be elevated in pregnancy. Clinical prediction rules or PE have not been validated in pregnancy. Pregnant patients with PE are younger and less likely to have comorbid conditions compared with nonpregnant patients, and generally appear “well” and in more than 60% o cases have normal arterial blood gases. Doppler ultrasound is the noninvasive test o choice in the pregnant woman with suspected DVT. In symptomatic patients with a high pretest probability but a negative test, serial Dopplers should be done and an MRV o the pelvis should be considered to look or an isolated iliac clot. A recent study ound that 60% o DVT in pregnancy is ound in the proximal veins without evidence o cal thrombosis, suggesting that propagation rom cal vein clots may not be the mechanism o proximal thrombosis in pregnancy. Chest x-ray and ECG are help ul in a patient with suspected PE to rule out other causes. Both ventilation-per usion lung scan

Management Treatment o VTE in pregnancy involves anticoagulation with lowmolecular-weight heparin (LMWH) or un ractionated heparin (UFH). Dosing is weight based, and may require increases with increasing gestation. War arin is a known human teratogen and its use in pregnancy is contraindicated or this indication. Table 221-16 lists medications or treatment o acute DVT and PE in pregnancy. Most centers maintain patients on ull therapeutic anticoagulation or the rest o their pregnancy until 6 weeks postpartum or at least 6 months, whichever is longer. Trials investigating lowering the intensity o anticoagulation a ter 4 to 12 weeks are currently

TABLE 221-16 Medications for Treatment of Venous Thromboembolism in Pregnancy Drug Un ractionated heparin

Dose 80 units/kg bolus, then 18 units/kg/h

Route Intravenous

Enoxaparin

1 mg/kg

Subcutaneous (SQ)

Tinzaparin Dalteparin

175 units/kg 200 units/kg

SQ SQ

Frequency Continuous, with dose adjustment using a PTT values Every 12 h. Due to increased clearance once daily dosing at 1.5 mg/kg may not be adequate Every 24 h Every 24 h

C H A P T E R 2 2 1 C o m m o n M e d i c a l P r o b l e m s i n P r e g

underway, but this practice has not yet been validated in pregnancy. LMWH is the pre erred agent in pregnancy, and has been associated with less thrombocytopenia and osteoporosis. Weight gain, increased blood volume, and increased clearance with pregnancy progression may require change in dosing, but this is usually guided by checking peak anti-Xa levels, which are done monthly. Peripartum management o anticoagulation can be challenging. Epidural analgesia or pain control during labor or spinal anesthesia may be necessary or an operative delivery. Guidelines rom the American society o Regional Anesthesia and Pain management (ASRA) recommend that in patients on therapeutic doses o LMWH, regional anesthesia be delayed at least 24 hours a ter last dose o LMWH injection to decrease the risk o spinal hematoma. This may be possible in a patient undergoing an elective induction o labor, but in most cases, the onset o labor cannot be predicted. We there ore switch the patient over to subcutaneous un ractionated heparin in the last month o pregnancy, two or three times a day, at a dose su cient to keep the mid-interval aPTT approximately twice normal. The patient is instructed to stop heparin injections at the rst sign o labor and aPTT is monitored closely once the patient is admitted to the hospital. Provided the aPTT is normal, regional anesthesia can be used with no contraindication. Following delivery, LMWH can be resumed 24 hours a ter removal o epidural or spinal catheter. In the postpartum period, war arin can be sa ely used, even in breast eeding mothers. Anecdotal evidence suggests that there is increased incidence o bleeding rom surgical sites during the overlap o war arin and LMWH. In patients who have had an operative delivery, we usually start war arin 2 weeks a ter delivery, to avoid the risk o surgical bleeding. Women with prior VTE are believed to have a higher risk o recurrent VTE in a subsequent pregnancy. There is evidence to suggest that this is especially true in patients whose rst event was related to pregnancy, puerperium, or oral contraceptive use. An underlying thrombophilia and a amily history o VTE are considered additional risk actors. Thromboprophylaxis is there ore recommended in these patients in subsequent pregnancies. Table 221-17 lists some anticoagulant prophylaxis regimens in pregnancy and the postpartum period. Prophylaxis needs to be continued or 6 weeks postpartum.

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(V/Q scan) and CT angiogram can be sa ely used in pregnancy or diagnosis o PE. Fetal radiation exposure with either o these tests is minimal (Tab le 221-15). In the majority o cases o atal PE in the UK. Con dential Enquiry into Maternal Mortality, the diagnosis was not made antemortem because o the mistaken belie that diagnostic testing would be harm ul to the etus. Pulmonary angiogram is usually reserved or severe cases in which localization o embolus is necessary prior to embolectomy.

INR, international normalized ratio; SQ, suncutaneously; UFH, un ractionated heparin.

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CT angiogram Ultrasound MRI/MRA/MRV Upper GI series Lumbar spine series Barium enema Complete IVP Head CT CT abdomen

1. Enoxaparin 40 mg SQ once daily until 20 wk gestation, then 40 mg twice daily. At 36-wk gestation, switch to UFH 10,000 units SQ twice daily until delivery 2. UFH 5000 units SQ twice daily in the irst trimester, 7500 units SQ twice daily in the second trimester, and 10,000 units SQ twice daily in the third trimester Suggested regimens or postpartum prophylaxis 1. Enoxaparin 40 mg SQ once daily 2. War arin, with target INR o 1.5-2 UFH 5000 units SQ twice daily

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Pulmonary angiogram

Radiation Exposure (RADS) 1 wk

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Mania with psychosis

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Intermittent > 2 wk

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Depression with psychosis

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Chronic, > 1 mo to years

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Delusion disorder

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Chronic, years

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Schizoa ective disorder

May progress to schizophrenia.

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Acute, > 4 wk and 1 mo o psychotic symptoms, > 6 mo o behavior change. R/O mood disorder, substance abuse and medical causes. Functional decline occurs. Symptoms o psychosis and mood disorder are equally prominent. > 2 wk o psychosis without mood symptoms needed or diagnosis. Prominent nonbizarre delusion(s). No hallucinations or minimal. Depression is primary. Content o psychosis o ten congruent with mood.

Persistence o symptoms in 30%-60% o patients. Some recovery is possible in most.

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Course and Duration Acute, days to < 4 wk

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Disorder Brie psychotic disorder

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TABLE 225-2 Disorders with Psychosis

Outcome is better than schizophrenia.

Personality is preserved. Function o ten preserved. Outcome better than schizophrenia. Responds well to electroconvulsive therapy. Outcome better than schizophrenia. Medical causes not uncommon and should be ruled out irst. Psychosis may persist days to weeks a ter abstinence. May require requent parenteral antipsychotics in small doses rather than bolus or single large dose.

Low doses o antipsychotics may be su icient. Higher doses o medications o ten not well tolerated. Higher risk o tardive dyskinesia.

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TABLE 225-3 Medical Conditions that May Manifest Psychosis

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Disorders System/Cause Common * Uncommon † Endocrine Addison, Cushing, hyper and hypothyroidism Hyper and hypoparathyroidism, pituitary disorders including Sheehan syndrome In ections Lyme disease, pneumonia Diphtheria, legionnaire disease, malaria, typhoid In lammatory Acute rheumatic ever, systemic lupus (cerebritis, Temporal arteritis vasculitis), sarcoidosis Metabolic Diabetic ketoacidosis, hepatic encephalopathy, Acute intermittent porphyria, Niemann Pick, hypoglycemia, hypoxia, hyponatremia, uremia Tay-Sachs Nutritional Vitamin B1 de iciency (Wernicke-Korsako Folic acid de iciency, niacin de iciency (pellagra) syndrome), B12 de iciency Pharmacologic Anticholinergics, antiobesity, antiparkinsonian: Antacids: cimetdine; antihistamines; levodopa, partial agonists, steroids, antihypertensives: clonidine, propranolol; antisympathomimetics in lammatories: cyclosporin, NSAIDs, salicylate, steroids; antineoplastics: methotrexate, 5- luorouracil; cardiac: digoxin, antiarrhythmics Substance abuse Alcohol, amphetamines, cocaine, cannabis Lysergic acid diethylamine (LSD), belladonna (see Table 225-4) alkaloids, phencyclidine (pcp), mescaline, psilocybin Toxic Carbon monoxide poisoning, industrial toxins, heavy metal poisoning (eg, lead, mercury) Trauma Epidural hematoma, intraparenchymal hemorrhage, subarachanoid hemorrhage, subdural hematoma Central nervous system disorders CNS disorders Multiple sclerosis, normal pressure hydrocephalus, NMDA receptor antibody encephalitis, Prion disease seizure disorders lobe Basal ganglia disorders Parkinson disorder Huntington disease, Wilson disease, Fahr disease CNS in ections HIVencephalopathy, any encephalitis, meningitis Herpes encephalitis, rocky mountain spotted ever, syphilis Dementias Alzheimer disease, Vascular dementia Pick disease, Creutz eld-Jacob disease Space occupying lesions Cerebral neoplasm Cerebral abscess, intracranial aneurysm, angioma Vascular Cerebrovascular events, hypertensive encephalopathy Congenital disorders Developmental Autism, intellectual disability, Tourette syndrome Genetic: other Down syndrome (Trisomy 21) Adrenoleucodystrophy (X-linked), Kline elter syndrome (XXY), Mar an syndrome (Chromosomes 5, 15), mitochondrial disorders, Prader-Willi (15q), velocardio acial syndrome (22q) Common: either the medical condition is common or psychosis as a mani estation is common. † Uncommon: either the medical condition is uncommon or psychosis as a mani estation is uncommon. *

various mood and behavior e ects including psychosis. Visual and tactile hallucinations are o ten a clue to an underlying physical or pharmacologic etiology. The psychosis may virtually mimic any o the unctional disorders and it is the detection o a physical cause by history, examination, or testing that establishes the medical etiology. The course o the psychosis in these conditions is highly variable and dependent on the underlying disorder. In chronic conditions, such as lupus, multiple sclerosis, seizure disorder, and hepatic and renal ailure, psychosis may mani est recurrently. An interesting although not pathagnomonic distinction between psychoses secondary to a general medical condition and schizophrenic disorders is the absence o negative symptoms in the ormer. PSYCHOSIS INDUCED BY SUBSTANCE ABUSE Table 225-4 lists the common substances o abuse that may maniest with psychosis. Visual and tactile hallucinations are common. Alcohol-induced psychosis may mani est with classic paranoid delusions and hallucinations and may easily be misdiagnosed as 1836

schizophrenia. In LSD psychosis, temporal lobe phenomena such as experiences o deja vu and jamais vu are not uncommon. Classic substance-induced psychosis should resolve within days o abstinence. However long-term use especially o alcohol may lead to persistent hallucinosis. When the psychosis is active, it is important to treat it adequately with antipsychotic medications and supportive therapies as well as standard withdrawal protocols. In recent years, designer drugs have emerged that cause or contribute to psychosis such as those containing the synthetic cannabinoid cannabicyclohexanol (“Spice”), methylenedioxy amphetamine (“Sally”, “Sass”) and methylenedioxymethamphetamine (MDMA) (“Ecstacy”,”Molly”). Routine urine drug screens may not identi y these substances warranting more specialized testing. ASSESSMENT

■ PSYCHIATRIC HISTORY AND EXAMINATION Assessment should start with a ocus on current symptoms, their duration, severity, and impact on daily unction, and then proceed

■ MEDICAL HISTORY, REVIEW OF SYSTEMS, AND LABORATORY ASSESSMENT It is imperative that all patients presenting with any psychotic symptom or behavior receive a proper medical workup including medical history, review o systems, and required testing. It is not, however, appropriate to order tests without a clinical indication, or example head CT, EEG, or CSF studies. Prenatal, birth, and early developmental history needs to be gathered rom patient, amily, or collateral source to rule in or out genetic, congenital, and developmental conditions known to mani est with psychoses (Table 225-3). Laboratory assessment has two main purposes: (1) to rule in or out speci c medical causes suspected rom the history and examination, and (2) to assess or conditions commonly comorbid with chronic psychotic disorders, such as anemia, obesity, hypertension, cardiac disease and diabetes. It should be remembered that patients with chronic mental illness are at a 1.5 to 2 times higher risk o having common systemic medical disorders.

■ NEUROLOGIC ASSESSMENT It is appropriate or a patient having a psychotic illness to be assessed neurologically with an EEG, brain scan, and neuropsychological testing at least once in the course o his or her illness, pre erably early on. In cases o new-onset psychosis and psychosis in the elderly person, such testing is more likely to yield clinically signi cant ndings, such as neurodevelopmental abnormalities, seizure oci, or atrophic, vascular, and neoplastic lesions. Following the above, a complete mental status examination should be conducted to assess current positive and negative symptoms o psychosis as well as mood and cognitive unctions such as attention, orientation, and memory. The mini–mental status examination is a handy tool to assess the latter. Equipped with in ormation rom the histories, examination and test results, a diagnosis may be arrived at guided by DSM-5 criteria. TREATMENT OF ACUTE PSYCHOSIS The physician has the option o choosing rom many available antipsychotic medications, although the evidence to date suggests

C H A P T E R 2 2 5 A s s e s s m e n t a n d M a n a g e m e n t o P s y c h

A detailed substance abuse history is a necessary part o the workup o psychosis and should cover all commonly abused substances, especially those known to cause psychosis (Table 225-4). A urine test or common drugs o abuse, and, i indicated, additional blood or urine tests or toxicology, should be ordered.

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■ SUBSTANCE USE HISTORY AND TESTING

First-generation antipsychotics (FGA) (see Table 225-5), also known as typical antipsychotics are e ective with positive psychotic symptoms but have a higher potential to cause extrapyramidal e ects, such as dystonia, parkinsonism, akathisia, and tardive dyskinesia. The most widely prescribed typical antipsychotic is haloperidal (Haldol). Other available FGA medications rom the phenothiazine class are f uphenazine (Prolixin), trif uperazine (Stelazine), perphenazine (Trila on), and chlorpromazine (Thorazine). Nonphenothiazine FGA antipsychotics are thiothixene (Navane), loxapine (Loxitane), and molindone (Moban). All these agents are thought to reduce psychosis, predominantly through the blockade o dopamine-2 receptors in the midbrain-limbic circuits. Second-generation antipsychotics (SGA) are used more widely in practice due to reduced extrapyramidal e ects, and are virtually the rst line o treatment. These include, in order o approval by the FDA, clozapine, risperidone (Risperdal), olanzapine (Zyprexa), quetiapine (Seroquel), ziprasidone (Geodon), ariprazole (Abili y), paliperidone (Invega), Iloperidone (Fanapt), Asenapine (Saphris), lurasidone (Latuda) and brexipiprazole (Rexulti). Clozapine, the rst atypical antipsychotic agent is a very e ective antipsychotic with proven superiority in re ractory schizophrenia, however it has additional toxicities such as agranulocytosis, seizure, pluritis and myocarditis and is restricted or use in re ractory patients. Its use requires registration with the risk mitigation program called clozapineREMS program, and includes mandatory monitoring o the absolute neutrophil count (ANC), weekly or 6 months, biweekly or 6 months and then monthly therea ter. In determining the minimum ANC threshold to start or resume clozapine, special consideration is given or persons with benign ethnic neutropenia. The SGAs are moderately dopamine blocking and also evidence antagonism to serotonin-2 receptors. Aripiprazole (Abili y) and Brexipiprazole (Rexulti) are also considered as atypical SGA because o the low potential or EPS, although their mechanism o action is di erent; these two agents are partial dopamine agonists. A scale o chlorpromazine-equivalent units (CPZ units) is available to convert the dose o one typical FGA to that o another, and can be approximated to the atypical SGAs as well (Table 225-5).

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to past psychiatric history, substance abuse history, and brie psychosocial history including current living situation and support network. A separate history should be obtained or unsa e behaviors including sel -injurious behaviors, suicidal ideation, intention, plans and attempts, and any ideas/behaviors o aggression/violence toward people and property.

ANTIPSYCHOTIC MEDICATIONS

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Substances Known to Induce Psychosis Alcohol Cannabis: marijuana, synthetic cannabis (ingredient o “K2,” “Spice”) Hallucinogens: ketamine, LSD, mescaline, phencyclidine (angel dust), psilocybin, etc Inhalants: amyl nitrate, gasoline, paint, paint thinners, etc Opioids: morphine, oxycodone, hydromorphone Stimulants: amphetamines, metamphetamines, cocaine, methylphenidate (Ritalin), designer drugs (MDMA or Ecstacy)

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TABLE 225-4 Substance-Induced Psychosis

they are roughly equal in e cacy but vary widely in their side e ects. E ect on the comorbid medical conditions, such as obesity, diabetes, cardiac disorders, and neurologic disorders, and any in ormation available rom prior experience o the patient, can help in orm this decision.

DOSING The antipsychotic agent is started at an initial dose o approximately 100 CPZ units, or example, 2 mg o haloperidol, or 2 mg o risperidone, or 100 mg o quetiapine, and titrated up every 1 to 2 days until su cient control o symptoms is achieved. Additional doses o the drug may be used on an as-needed basis to supplement the regular dose. The dosing is illustrated in two cases using haloperidol and quetiapine as examples. The drug choice in the examples is arbitrary and the dosing is just one example o standard practice. Other dosing regimens may be substituted without loss o e cacy. RESUMPTION OF TREATMENT FOR PRE-EXISTING PSYCHOSIS Medical illnesses o ten act as stressors and escalate pre-existing psychosis, and o ten patients become noncompliant with medications. An antipsychotic should be reinstituted at the soonest possible time. In others who remain compliant, continue the antipsychotic. In both cases, it is best to use the antipsychotic that the patient was receiving most recently. In noncompliant patients, the starting dose may have to be lower than the most recently prescribed dose and 1837

Generic and Common Brand Names FGA (Typical) Chlorpromazine (Thorazine)

Mechanism of Action and DA2 Receptor Potency

Daily Dose * in mg

D2 antagonist, low

200-1000

Loxapine (Loxitane) Molindone (Moban) Thiothixene (Navane) Perphenazine (Trila on)

D2 antagonist, medium D2 antagonist, medium D2 antagonist, medium to High D2 antagonist, medium to high

25-200 25-225 10-80 8-64

Tri luperazine (Stelazine) Fluphenazine (Prolixin) Fluphenazine decanoate long-acting inj Haloperidol (Haldol) Haloperidol decanoate, long-acting inj SGA (Atypical) Risperidone (Risperdal) Risperidone long-acting inj, (CONSTA) Paliperidone (Invega) Paliperidone palmitate long acting inj (Invega Sustenna) Olanzapine (Zyprexa) Olanzapine pamoate, long-acting inj, (Relprevv) Quetiapine (Seroquel) Ziprasidone (Geodon) Arpiprazole (Abili y) Aripiprazole long acting inj (Abili y Maintenna) Asenapine (Saphris)

D2 antagonist, medium to high D2 antagonist, high

5-60 5-60 12.5-100 every 3 wk 2-20 25-200 every 4 wk

EPS, TD EPS, TD

Hypotension, sedation, prolactinemia, weight gain, EPS at higher doses

D2, 5-HT2, high

1-6 12.5-50 Q2 wk 6-18, 117-234 Q4 wk 5-20 150-405 Q4 wk 100-800 40-160 5-30 300-400, Q4 wk 5-20

Iloperidone(Fanapt) Lurasidone (Latuda)

D2,5-HT2 antagonist, High D2, 5-HT2, medium

2-24 40-80

Brexipiprazole

Partial D2 agonist, 5-HT2 antagonist, high D2 antagonist, low 5-HT2 antagonist, high

2-4

Common Adverse Events

Comments

Hypotension, sedation, EPS, TD Sedation, EPS, TD Activation, EPS EPS, TD EPS, TD

First available antipsychotic

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TABLE 225-5 Commonly Available Antipsychotic Medications

Clozapine (Clozaril)

D2 antagonist, high

D2 and 5-HT2 antagonist, high

D2 and 5-HT2 antagonist, high

D2 and 5-HT2 antagonist, medium to high D2 and 5-HT2 antagonist, low D2 and 5-HT2 antagonist, medium Partial D2 agonist, 5-HT2 antagonist, high

100-800

EPS, prolactinemia, TD

Sedation, dizziness, EPS at higher doses

Used in CATIE, largest nonindustry trial

Most widely used typical antipsychotic

Active metabolite o risperidone

Hypotension, sedation, weight gain, DM Hypotension, sedation Hypotension, prolonged QTc Activation, nausea

Oral numbness, dizziness, somnolence, akathisia, weight gain

Sublingual

Somnolence, dizziness, nausea, Parkinson Activation, agitation, nausea Sedation, weight gain, hypotension, seizures, agranulocytosis, DM

ANC monitoring required (clozapineREMS.org)

5-HT2, serotonin 2 receptor; D2, Dopamine 2 receptor, DM, diabetes mellitus; EPS, extrapyramidal symptoms; TD, tardive dyskinesia; ANC, absolute neutrophil count. * Dose ranges given re lect those used in common clinical practice.

gradually titrated up to the ull dose to guard against acute adverse e ects. As treatment proceeds, the dose may need to be increased, sometimes beyond the previous maintenance dose. MANAGEMENT OF ADVERSE EFFECTS Common side e ects include extrapyramidal e ects such as dystonia, treated with intramuscular diphenhydramine, and Parkinsonism, treated with benztropine 1 to 2 mg two to three times a day. Other anticholinergics that may be substituted or benztropine include trihexyphenidyl (Artane) or biperiden (Kemadrin). Akathisia is a subjective sense o unease with objective motor restlessness that 1838

may arise a ew days into treatment, and is treated with lorazepam (Ativan) 1 to 2 mg two or three times a day, or propranolol (Inderal) 10 to 40 mg two or three times a day. MANAGEMENT OF SEVERE AGITATION The use o as-needed (PRN) antipsychotic medication has been mentioned earlier. Sometimes it is necessary to use two antipsychotics or managing acute agitation. For example, a patient may be on quetiapine and while the standing dose is being titrated up, additional as-needed haloperidol by injection (intramuscular or intravenous), such as 2 to 5 mg every 4 to 6 hours may be given.

MILIEU AND PSYCHOSOCIAL THERAPIES Patients exhibiting psychosis are best cared or in a private room or their own sa ety and com ort as well as that o other patients. In case o severely agitated, destructive, and/or disruptive behaviors, the use o so t restraints may be necessary till the medications are dosed appropriately and are e ective. In case o unsa e behavior including sel -injurious ideation and behaviors or suicidal behavior, it is recommended that the patient be on one-on-one observation, with 24/7 visual contact and arms-length supervision as warranted by the intensity/severity o the sa ety condition. The issue o keeping the patient on a medical-surgical unit versus trans er to a psychiatric unit is o ten di cult. Clearly, i the acute medical-surgical conditions that the patient is in the hospital or have been addressed or are subsiding, then it is appropriate to promptly move the patient to a dedicated psychiatric unit. On the other hand, i the medical-surgical problems need active management including interventions, such as intravenous in usions, telemetry, requent medical-neurologic examinations, postoperative surgical care, requent or extensive wound care, or care o extensive burns etc, then it is recommended to keep the patient on the appropriate unit, while initiating or continuing the psychiatric care. Patients with psychosis should not receive too much stimulation rom the environment (lights, noise, television, medical rounds with large numbers o people, requent interruptions by sta , etc); care should be taken to minimize this. The patient should be allowed to participate in sel -care activities as tolerated by their medical condition. Paranoid patients may eel urther threatened by loss o autonomy and control. Visits by caregivers and visitors should be brie and structured. Emotionally neutral activities are pre erred rather than ree access to health and news channels on TV, movies, etc. A social worker or care coordinator should work with the patient and signi cant others to address any external stress and environmental manipulation, as easible. The patient’s dignity should be upheld at all times. The patient should be respected and kept ully in ormed o all health care plans and decisions, albeit with brie

C H A P T E R 2 2 5 A s s e s s m e n t a n d M a n a g e n P s y c h o

Physicians will requently encounter situations wherein the capacity o a patient with psychosis is called into question. This may arise i and when a patient re uses or does not cooperate with routine care, speci c medical-surgical procedures or testing or treatment, psychiatric treatment, and/or requests premature discharge or attempts to leave. The situation may be urgent or nonurgent and elective. In each case except the most pressing situation, it is prudent to obtain a psychiatric consultation, which should include an opinion on the capacity o the patient to make a speci c medical decision. Simple instruments are available to assess key areas pertaining to capacity. In an urgent situation, the physician may initiate interventions to save li e or avoid permanent injury while seeking a consultation and consent rom an appropriate entity in accordance with hospital policy and local, state, and ederal law. In less urgent situations, the consultation and capacity assessment and appropriate consenting should precede the intervention. Typically, a patient is considered to have capacity unless and until assessed to be otherwise. Such assessment may be per ormed by any physician although it is better to have a licensed mental health pro essional, pre erably a psychiatrist, conduct this. Although state laws vary considerably, most states allow or urgent medical treatment against the wishes o an individual, i (1) lack o treatment is likely to result in permanent injury or death, (2) the individual is assessed to not have capacity to make the decision, and (3) consent has been obtained rom an appropriate third party, typically legal next o kin or a local magistrate. Continuation o the treatment and initiation o less urgent interventions including non–li e-saving interventions o ten require an assessment o capacity, recommendation by an independent physician, pre erably a mental health pro essional, approval by an ethics or equivalent committee, and/or consent by a magistrate.

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As soon as psychosis is suspected or history o a pre-existing psychotic disorder is obtained, a psychiatric consultation is recommended. However, nonpsychiatric physicians may manage a psychosis i such consultation is not available, especially i the preexisting psychosis is a chronic condition and is stable or in remission. In this case, simply continuing the previous treatment with attention to proper dosing may su ce. However, i the psychosis is new in onset or has relapsed, it is recommended that a psychiatric consultation be obtained as soon as possible. In hospitals where such consultation is not easible and active psychosis persists beyond 3 days, the patient should ideally be trans erred to a hospital where such consultation is available or to a psychiatric unit, as appropriate. Psychiatric consultation is also recommended in case o questions regarding capacity to make medical decisions and possible involuntary treatment. The consultation should be ongoing till the psychosis is resolved, ully stabilized, or the patient is discharged.

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Patients with pre-existing psychosis are o ten on a mood stabilizer such as divalproex sodium or lithium; antidepressant medications; benzodiazepines, such as lorazepam or clonazepam; and/or hypnotic-sedatives such as zolpidem (Ambien), zaleplon (Sonata) and eszopiclone (Lunesta). In such cases, it is best to coordinate the care with the outpatient psychiatrist by obtaining his or her opinion on continuation or discontinuation o these medications. In the absence o any such input, it is prudent to use the lowest e ective dose o these agents or active symptoms, and not blindly resume all psychotropics. The exceptions to this rule are clozapine, high-dose benzodiazepines (eg, >4 mg o lorazepam per day), and selective serotonin receptor inhibitors (paroxetine, sertraline, citalopram, etc), in which the potential or withdrawal e ects is high. Fluoxetine (Prozac) has a long hal -li e and is sel -tapering.

PSYCHIATRIC CONSULTATION

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ADJUNCT MEDICATION

and succinct in ormation. As discussed in more detail later in this chapter, consent should be obtained or all procedures, testing, and treatment outside routine care.

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Second-generation antipsychotics are also available or intramuscular injections and include ziprasidone 10 to 20 mg intramuscular every 6 to 8 hours, aripiprazole 9.75 mg intramuscular every 8 hours, and olanzapine 5 to 10 mg intramuscular every 6 to 8 hours. Lorazepam 1 to 2 mg as an intramuscular or intravenous injection given every 4 to 6 hours, may also be used to control psychotic agitation. It is not recommended to use more than two antipsychotics in any orm or managing most cases. The potential or greater adverse e ects such as excessive sedation, orthostasis and alls, and EPS is increased with polypharmacy, while not much is added to e cacy. So t restraints to the arms and legs may have to be used to prevent injury to sel or others.

COMPLICATIONS AND MANAGEMENT The complications o an active psychosis (Table 225-6) include behavioral and/or medical events. These include severe agitation, disruptive behavior, unsa e behaviors including suicidal ideation and attempt, aggressive and violent behavior, leaving against medical advice, elopement, and escape. These behaviors may result rom psychotic experiences such as hallucinations and delusions including paranoid ears, or may be the result o independent psychiatric disorders such as substance abuse and personality disorder. When 1839

Behavioral Neglect o sel -care

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TABLE 225-6 Behavioral and Medical Complications of Psychosis

Withdrawal and catatonia

Injury to sel and others including homicide Suicide Depression Amotivation, social isolation, de icit states, institutionalization CPK, creatine phosphokinase.

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Physical/Laboratory Exacerbation o medical disorders such as hypertension, diabetes, seizures, and in ections Dehydration, electrolyte imbalance Autonomic arousal and hyperactivity Injuries ( rom restraint): so t tissue, ractures, etc Muscle breakdown, increased CPK, acute renal ailure Starvation, ketosis, acidosis, and metabolic disturbances Sudden death

1840

assessed to be the result o psychosis, such behavior is best treated with a combination o antipsychotic medication and supportive therapy/counseling, including education o patient/ signi cant other. I assessed to be rom actors other than the psychosis, psychosocial interventions including negotiation with the patient, liaison by a psychiatrist, or assistance by a social worker or care coordinator may be help ul, depending on the issues. Medical complications may include compromised f uid intake, electrolyte imbalance, poor nutrition and weight loss, autonomic hyperactivity including tachycardia, hypertensive crisis, hyperthermia, muscle rigidity, increased creatine kinase, and acute renal ailure. The syndrome o malignant catatonia may start as a state o psychotic excitement and progress to catatonic stupor, and many o the physical complications noted above may be part o this syndrome. Its eatures overlap signi cantly with those o neuroleptic malignant syndrome. Medical complications rom psychotropic medications may include adverse e ects such as extrapyramidal symptoms and signs, orthostatic hypotension, excessive sedation, liver enzyme abnormalities, blood dyscrasias including leucopenia, mild leucocytosis, changes in ECG including prolongation o QT interval, seizures, and micturition di culties including rarely distended bladder. The combination o haloperidol and lithium was reported to be associated with a toxic encephalopathic syndrome, although this entity remains controversial. All neuorleptic agents have been associated with neuroleptic malignant syndrome, especially those with higher D2-blocking property, such as haloperidol. Clozapine has a 0.5% to 1.0% risk o inducing agranulocytosis, 2% to 5% risk o seizure, and is (rarely) associated with pleuritis and myocarditis. Olanzapine has sometimes been reported to cause an acute ketoacidosis. Clozapine and olanzapine when combined with benzodiazepines such as lorazepam, especially when given intramuscularly have been associated with apneic episodes, and rarely death. Medical syndromes rom the withdrawal o psychotropic agents may include SSRI discontinuation syndrome mani ested by motor restlessness, insomnia, nausea, and vomiting, sense o con usion, myoclonic jerks, and rarely generalized seizure. Clozapine withdrawal may mani est a similar syndrome. Withdrawal rom benzodiazepines

may lead to tachycardia, hypertension, and seizures. It is there ore prudent to taper these medications rather than sudden discontinuation. CONCLUSION Psychosis is o ten seen on medical-surgical units as a comorbid condition. Acute psychosis constitutes an emergency and should be assessed and treated as such. Behavioral and medical complications may result rom untreated or poorly treated psychosis. Psychosis is a syndrome and depending on the underlying disorder, its course and outcome will vary. There are both acute- and short-lasting unctional psychotic disorders and chronic disorders. Medical actors and substances o abuse should be considered in the assessment o psychosis. Antipsychotic medications are the mainstay o treatment and care ul attention should be given to the selection o the agent and dosing. Antipsychotics have many side e ects, which play a signi cant role in the choice o medication. Psychosis in the context o an acute medical condition may be success ully treated on a medical unit and most psychoses will resolve or may be controlled with proper treatment. Psychiatric consultation is recommended and can be help ul in determining the nature o the psychosis, the choice o antipsychotic medication, the capacity to consent, detecting adverse e ects and their management, and making recommendations on a tercare. Brie psychosocial interventions such as structured activity, patient counseling, involving signi cant others, and care coordination increases the chances o success ul management and better outcomes. Follow-up care with a psychiatrist or mental health clinic is an integral part o the management o psychotic disorders.

SUGGESTED READINGS American Psychiatric Association. Diagnostic and Statistical Manual o Mental Disorders, 5th ed., (DSM-5). Washington, DC: American Psychiatric Association Press; 2013. Buchanan RW. Clozapine: e cacy and sa ety. Schizophr Bull. 1995;21:579-591. Citrome LL. A review o the pharmacology, e cacy and tolerability o recently approved and upcoming oral antipsychotics: an evidence-based medicine approach. CNSDrugs. 2013;27(11):879-911. Davidson L, McGlashan TH. The varied outcomes o schizophrenia. Can J Psychiatry. 1997;42:34-43. Fei el D. Rationale and guidelines or the inpatient treatment o acute psychosis. J Clin Psychiatry. 2000;61(14):27-32. Freudenreich O, Stern TA. Clinical Experience with the management o schizophrenia in the general hospital. Psychosomatics. 2003;44:12-23. Go DC, Henderson DC, Manschreck TC. Psychotic patients. In Cassem NH, ed. Massachusetts General Hospital Handbook o General Hospital Psychiatry. St Louis, MO: Mosby; 1997, 149-171. Kane JM, Leucht S, Carpenter D, et al. The expert consensus guideline series. optimizing pharmacologic treatment o psychotic disorders. introduction: methods, commentary, and summary. J Clin Psychiatry. 2003;64:5-19. Lamdan RM, Ramchandani D, Schindler BA. The chronically mentally ill on a general hospital consultation-liaison service. their needs and management. Psychosomatics. 1997;38:472-477. Richards CF, Gurr DE. Psychosis. Emerg Med Clin North Am. 2000;18: 253-262, ix.

226

CHAP TER

Eating Disorders Angela S. Guarda, MD Daniel F. Ruthven, MD Graham W. Redgrave, MD

Key Clinical Questions 1

When should a hospitalist suspect an eating disorder? What questions aid in making the diagnosis? What screening tests are indicated?

2

When is emergent hospitalization warranted?

3

What are the complications o starvation and o binge/purge behaviors?

4

What is re eeding syndrome?

5

What are the evidence-based treatments or eating disorders?

6

What ethical considerations are speci ic to the treatment o eating disorders?

INTRODUCTION Medical morbidity associated with eating disorders is high; most hospitalists will encounter patients with these disorders, so knowledge o the presentation, natural history, complications, and medical management o these conditions is important. Patients with eating disorders may be admitted through emergency rooms in the setting o an acute event such as syncope or a seizure, or re erred by their primary care provider or an abnormal electrocardiogram or or laboratory values warranting admission or medical monitoring and stabilization. The majority o patients are likely to have anorexia nervosa (AN), but some may have bulimia nervosa (BN). Others may present with an atypical eating disorder in which abnormal eating behavior is not associated with drive or thinness or ear o being at. Eating disorders are best thought o as disorders o motivated behavior and are similar to addictions. As with substance abuse disorders, patients exhibit a narrowing o their behavioral repertoire. They develop increasingly driven ritualized behaviors and progressive unctional impairment. The vast majority o a ected individuals are emales with the li etime prevalence o AN and BN in women estimated at 0.9% and 1.5%, respectively. Although less common in males, it is also the case that males with eating disorders are less likely to reach medical attention, and community rates o eating disorders in men and boys are higher than the 10% male gender prevalence observed in clinical samples. Mortality or AN is one o the highest amongst psychiatric conditions, with six old increase in standardized mortality rates. As eating disorders are motivated behavioral conditions, ambivalence toward and rank avoidance o treatment are common. Patients may conceal their behavior rom others and avoid pro essional help, complicating both diagnosis and management. When they do present or treatment, they are requently in crisis, seeking assistance in managing complications o their disorder, or because they are brought to treatment by others. Hal o all the community cases o AN and BN are undetected, underscoring the importance o recognizing signs and symptoms. Once identi ed, most patients are reluctant to engage in treatment, pre erring treatment on their own terms, picking and choosing interventions that eel best, rather than those that may be best or them. Knowing how to engage patients to seek e ective treatment is one o the most important challenges or the clinician. INDICATIONS FOR EMERGENT HOSPITALIZATION Medically unstable patients with eating disorders are ideally treated by a multidisciplinary team on a dedicated inpatient specialty unit, using a rehabilitative approach (including intensive behavioral and group therapy). Such programs are e ective in restoring weight in underweight patients and in normalizing eating behavior. In AN, weight restoration to a BMI o 19 to 21 is necessary though not usually su cient or recovery. Treatment should also address medical complications, interrupt unhealthy behaviors, establish a normal eating pattern, and use psychotherapeutic strategies to assist patients in challenging cognitive distortions that sustain their behavior. A ocus on relapse prevention and transition to outpatient treatment are critical components o long-term rehabilitation, especially in chronically ill patients who have become unctionally impaired as a consequence o their eating disorder.

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P A R T V I C l i n i c a l C o n d i t i

TABLE 226-1 Categories of Eating Disorders Anorexia nervosa (AN)

Bulimia nervosa (BN)

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Un ortunately, there are ew specialized hospital-based behavioral programs capable o managing medically complex cases, and access may be limited urther by insurance or nancial issues. As a result, patients are o ten admitted to hospitalist services or initial medical monitoring and stabilization. Reasons or emergent hospitalization can include hypokalemia or other serious electrolyte imbalances, hypoglycemic coma, symptomatic bradycardia, severe hypotension, dehydration, syncope, seizure, prolonged QTc interval, severe marasmus with BMI 5.5 mmol/L? ' No

Ye s

Type IV RTA e GFR < 30? No Type I vs II RTA

Ye s

Ure mic a cidos is

Figure 238 1 Evaluation of metabolic acidosis. alkali treatment o acute metabolic acidosis on either mortality or on cardiovascular per ormance. However, treating acute metabolic acidosis with alkali might be considered i arterial pH is less than 7.1. I alkali treatment is used, a target pH o no more than 7.2 is reasonable, as aggressive alkali therapy may have deleterious side e ects. Slow IVadministration o 50 to 100 mEq o NaHCO3, over 30 to 45 minutes, can be used. It is essential to monitor plasma electrolytes during the course o therapy, since the [K+] may decline as pH rises. Administration o large amounts o concentrated NaHCO3 in the orm o multiple ampules can cause acute hypernatremia because o the associated sodium load. Rapid intravenous alkali administration can acutely decrease the ionized calcium, which may impair cardiac unction. Patients with simultaneous intravascular volume depletion and metabolic acidosis may bene t rom volume resuscitation rom intravenous uids prepared rom the addition o 150 mmol sodium bicarbonate (three ampules) per 1 L o D5W.

■ HIGH AG ACIDOSIS The our most common causes o a high AG metabolic acidosis are lactic acidosis, ketoacidosis, ingested toxins, and renal ailure. There ore, the initial screening to di erentiate the high AG acidoses should include relevant history or evidence o drug and toxin ingestion, determination o blood lactic acid, glucose, ethanol, beta-hydroxybutyrate, blood urea nitrogen (BUN), and creatinine, inspection o the urine or oxalate crystals, and identi cation o

predisposing actors or lactic acidosis, such as hypotension, shock, cardiac ailure, leukemia, cancer, unrecognized bowel ischemia, thiamine de ciency, and drug or toxin ingestion.

■ LACTIC ACIDOSIS Lactic acidosis almost always indicates the presence o impaired tissue per usion, most commonly due to hypotension, arterial disease, or sepsis. Rarely, an unsuspected neoplasm produces lactic acid and is the causative actor. Identi ying and treating the underlying cause is central to therapy. Alkali therapy is usually reserved or severe acidemia (pH 10%

Urine pH

During alkali treatment > 5.5; chronic, no alkali treatment < 5.5 Hypokalemia; worsens with therapy

> 5.5

Usually ≤ 6.0

Hypokalemia; o ten improves with therapy

Increased

Increased

Hyperkalemia; correcting hyperkalemia can correct the RTA Usually normal

Serum K+

Ca 2+ excretion

FEHCO3 , ractional excretion o bicarbonate measured when the serum bicarbonate is normal. –

ammonia, present almost exclusively as urinary NH4+, is appropriately increased. In metabolic acidosis rom bicarbonate loss in diarrhea, the UAG is typically –20 to –50 mmol/L. The absence o a negative UAG indicates a ailure o urinary ammonia excretion to increase, and suggests that RTA or advanced CKD is the cause o the acidosis. Clinicians must recognize that the ormula used or the urine anion gap di ers rom that used or the plasma or serum anion gap. Not recognizing this di erence can lead to serious errors and incorrect diagnoses.

■ TYPE I RTA (DISTAL RTA) Type I RTA is characterized by hypokalemia, normal AG metabolic acidosis, low urinary NH4+ excretion (as re ected by a positive UAG), and a high urine pH (pH ≥6.5) in the presence o untreated metabolic acidosis. These patients commonly come to medical attention either because o growth retardation and ailure to thrive in children, or recurrent renal stone ormation in adults. Urinary citrate, an important inhibitor o urinary calcium oxalate crystallization, is decreased in distal RTA, contributing to the nephrolithiasis. Type I RTA in children is requently caused by genetic mutations in distal tubular ion transporters. In adults, type I RTA may result rom acute interstitial nephritis, or autoimmune diseases, such as systemic lupus erythematosus and Sjögren syndrome. Oral alkali supplementation, dosed at 1 mmol/kg/d, is the mainstay o therapy. Patients typically require 50% o the alkali as potassium citrate to treat the concomitant hypokalemia. Sodium alkali salts, such as sodium citrate or sodium bicarbonate, are used to correct the remainder o the metabolic acidosis, while avoiding excessive potassium supplementation

C H A P T E R 2 3 8 A c i d B a s e D i s o

FEHCO3–

Type II RTA is characterized by hypokalemia and nonanion gap metabolic acidosis. In contrast to type I RTA, urine pH in untreated type II RTA is ≤ 6.0. Many patients with type II RTA exhibit the Fanconi syndrome (type II RTA, glycosuria, generalized aminoaciduria, and phosphaturia). Causes o type II RTA include inherited genetic disorders, such as cystinosis, hereditary ructose intolerance, and Wilson disease, and acquired disorders, such as multiple myeloma, renal transplant rejection, and certain medications, including acetazolamide, i os amide, and the antiretroviral drug teno ovir. Teno ovir is currently a common cause o acquired Fanconi syndrome, characterized by the recent onset o impaired renal unction, with hypokalemia, nonanion gap metabolic acidosis, and glycosuria in a nondiabetic patient in an taking teno ovir or HIV or hepatitis B in ection. Identi ying and correcting the underlying causes are central to treating acquired orms o proximal RTA. I the underlying cause cannot be reversed, oral alkali therapy is used. Large amounts o bicarbonate, typically 10 to 15 mmol/kg/d, are required. As the serum bicarbonate increases, renal bicarbonate losses increase, causing the need or very high doses. Similar to type I RTA, 50% o the alkali should be given initially as a potassium salt such as potassium citrate, and 50% as a sodium salt, either sodium citrate or sodium bicarbonate. Doses o these are adjusted as necessary to normalize serum potassium and bicarbonate.

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> 3%

Chronic kidney disease and impairments o reninaldosterone axis

■ TYPE II RTA (PROXIMAL RTA)

d

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e

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Distal (Type I) De ective collecting duct H+ secretion Genetic disorders o the tubule in children; autoimmune disease, interstitial nephritis in adults > 3%

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Mechanism

Proximal (Type II) De ective proximal tubule HCO3– absorption Genetic disorders in children; myeloma, nephrotoxic medications in adults

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TABLE 238-5 Classification of Renal Tubular Acidosis

and development o hyperkalemia. The dosage o sodium and potassium alkali salts should be adjusted to obtain normal serum bicarbonate and potassium levels.

■ TYPE IV RTA Type IV RTA is characterized by hyperkalemia, normal anion gap metabolic acidosis, and disturbances in the renin-aldosterone axis leading to impaired release or action o aldosterone. Most patients have concomitant chronic kidney disease, most commonly diabetic nephropathy and interstitial nephritis. Other causes or contributing actors include HIV, sickle cell disease, urinary tract obstruction, lupus nephritis, amyloidosis, myeloma, adrenal insuf ciency, kidney transplant rejection, and a variety o medications, such as cyclosporine, angiotensin converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), NSAIDs, trimethoprim, heparin, and potassiumsparing diuretics. In patients with hyperkalemia and CKD, it may be dif cult to di erentiate type IVRTA rom uremic metabolic acidosis. We recommend correcting the hyperkalemia. I the metabolic acidosis does not resolve a ter hyperkalemia has been corrected then a component o uremic metabolic acidosis is present. The urine pH in most patients with type IV RTA is acidic, usually ≤ 6.0, but may be elevated. Acidosis is usually mild, and bicarbonate therapy may not be needed. In most cases, type IV RTA develops because hyperkalemia suppresses renal ammonia production and thus net acid excretion. Accordingly, decreasing dietary potassium is bene cial and o ten corrects the metabolic acidosis. Thiazide diuretics, which are more e ective at increasing renal potassium excretion then loop diuretics, may also be help ul. The robust thiazide-type diuretic metolazone is o ten help ul in patients with advanced CKD. Type IV RTA is rarely a result o primary adrenal insu iciency. These patients typically present with low blood pressure, hyperkalemia, and nonanion gap metabolic acidosis. The urinary pH will o ten be 6.5 or higher. The diagnosis o adrenal insu iciency can be con irmed with appropriate serologic tests. Treatment with glucocorticoids and mineralocorticoids is e icacious in correcting type IV RTA in this setting. In general, exogenous mineralocorticoids should be avoided in patients with chronic kidney 1949

P A R T V I

disease, as they may contribute to progression o chronic kidney disease and an earlier necessity or initiation o renal replacement therapy. We generally do not recommend discontinuing ACE inhibitors or ARBs in patients with type IV RTA, because these medications decrease cardiovascular events and slow the progression o chronic kidney disease.

Patients with metabolic alkalosis may be asymptomatic or present with delirium, cardiac arrhythmias, and neuromuscular irritability when the pH exceeds 7.55. This diagnosis is most commonly prompted by the recognition o the elevated serum bicarbonate in routine serum chemistry analyses in the asymptomatic patient. Occasional patients come to medical attention because o compensatory hypoventilation, which may lead to hypoxia, respiratory ailure, or pneumonia. Patients may have a history o diuretic use, vomiting, and poorly controlled hypertension. Laboratory values demonstrate an elevated arterial pH, increased serum HCO3–, and an increase in PaCO2 secondary to compensatory alveolar hypoventilation.

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Metabolic alkalosis: measure the urinary chloride level to assesses the renal ability to excrete excess bicarbonate. The urine chloride is only valid i diuretics have not been recently administered. Low urinary chloride, 20 mmol/L, indicates a chlorideunresponsive metabolic alkalosis. This indicates the presence o ongoing acid loss, occasionally through gastric acid loss, but typically rom persistent, mineralocorticoid-dependent, stimulation o renal acid excretion.

Metabolic alkalosis involves both a generation and a maintenance phase. The generation phase involves either acid loss, rom either loss o acidic gastric uid, increased renal net acid excretion associated with either hypokalemia or hyperaldosteronism, or decreased plasma volume, leading to a decreased volume o distribution or bicarbonate. The maintenance phase either involves total body chloride depletion, thereby impairing renal chloride-dependent bicarbonate excretion, or ongoing acid losses, typically either gastric uid or rom aldosterone-stimulated renal acid excretion. Assessment o the urine chloride may be help ul in di erentiating the di erent causes o the maintenance phase (Table 238-6). A low urine chloride, typically 20 mmol/L, indicates chloride-unresponsive metabolic alkalosis. These patients will typically not be helped with chloride supplementation. Instead, treating their ongoing gastric acid or renal acid losses is critical to their therapy. Hypokalemia directly stimulates renal acid excretion. Treatment o hypokalemia, i present, may be help ul. Many o these patients have a degree o hyperaldosteronism, either primary or secondary, and bene t rom treatment with either mineralocorticoid receptor blockers or 1950

TABLE 238-6 Cause of Metabolic Alkalosis Chloride-responsive (urinary chloride < 20) GI Nasogastric suction Vomiting/diarrhea Laxative abuse Villous adenoma Renal Diuretics Post-hypercapnea Re eeding alkalosis Cystic ibrosis (sweat losses) Chloride-resistant (urinary chloride > 30) Mineralocorticoid excess Primary or secondary aldosteronism Secondary aldosteronism (eg, CHF, renal artery stenosis, liver disease) Cushing syndrome Licorice ingestion Alkali load Citrate (trans usions) Acetate (TPN) Severe hypokalemia/hypomagnesemia

inhibitors o the renin-angiotensin system i there is evidence o secondary hyperaldosteronism. Direct inhibition o renal acid excretion, such as the carbonic anhydrase inhibitor acetazolamide, may also be use ul. Other causes o metabolic alkalosis include Bartter syndrome, Gitelman syndrome, Liddle syndrome, villous adenoma, and milk-alkali (calcium-alkali) syndrome.

■ TREATMENT The treatment o metabolic alkalosis depends on whether patient has chloride-responsive or chloride-unresponsive metabolic alkalosis. Patients with chloride-responsive metabolic alkalosis improve with chloride administration. I they are hypokalemic, this can be provided as potassium chloride. I the serum potassium is normal, then the chloride is administered as sodium chloride, typically as intravenous saline solution. Chloride-unresponsive metabolic alkalosis requires treatment o the underlying condition, and generally does not respond well to either NaCl or KCl administration. Very rarely, acid therapy may be necessary. Intravenous acid preparations include either HCl or NH4Cl, 100 mmol/L, and should be administered only through a central vein. NH4Cl should be avoided in patients with liver disease because it may precipitate hepatic encephalopathy. RESPIRATORY ACIDOSIS Respiratory acidosis is diagnosed by an increase in PaCO2 and decrease in pH. Patients may be minimally symptomatic, or acutely anxious, agitated, obtunded or comatose. Tremor, asterixis, and myoclonic jerking may be present on examination. Cerebral vasodilation may occur, with headaches and signs o raised intracranial pressure, such as papilledema, abnormal re exes, and ocal muscle weakness. Di erentiating acute rom chronic respiratory acidosis is critical or accurate diagnosis and treatment. Acute respiratory acidosis

RESPIRATORY ALKALOSIS The diagnosis o respiratory alkalosis depends on measurement o arterial pH and PaCO2. Other laboratory ndings may include a reduced serum K+ and elevated serum Cl–. Acute respiratory alkalosis is not usually associated with increased renal HCO3– excretion, but within hours net acid excretion is reduced. Acutely, HCO3– concentration alls by 2.0 mmol/L or each 10 mm Hg decrease in PaCO2. Chronic hypocapnia reduces the serum HCO3– by 4.0 mmol/L or each 10 mm Hg decrease in PaCO2. However, it is unusual to observe a plasma HCO3– 3-5 days), renal adaptation increases the HCO3– by 4 mmol/L or every 10 mm Hg increase in PaCO2. The serum HCO3– usually does not rise above 38 mmol/L. General anesthetics, sedatives, head trauma, alcohol, intracranial tumors, syndromes o sleep-disordered breathing, diseases o the motor neurons, neuromuscular junction and skeletal muscle, and improperly adjusted mechanical ventilation may result in respiratory acidosis. In a stable mechanically ventilated patient, respiratory acidosis may develop secondary to a sudden rise in CO2 production, as rom ever, agitation, sepsis, or over eeding. However, it is more o ten due to a all in alveolar ventilation rom worsening pulmonary unction or sudden occlusion o the upper airway.

ACKNOWLEDGMENTS Preparation o this chapter supported by grant unds rom the NIH (R01-DK045788) and the Department o Veterans A airs (1I01BX000818).

SUGGESTED READINGS Brent J. Fomepizole or ethylene glycol and methanol poisoning. N Engl J Med. 2009;360:2216-2223. Kamel KS, Halperin ML. Acid-base problems in diabetic ketoacidosis. N Engl J Med. 2015;372:546-554. Karet FE. Mechanisms in hyperkalemic renal tubular acidosis. J Am Soc Nephrol. 2009;20:251-254. Kraut JA, Kurtz I. Toxic alcohol ingestions: clinical eatures, diagnosis, and management. Clin J Am Soc Nephrol. 2008;3:208-225. Kraut JA, Madias NE. Lactic acidosis. NEngl J Med. 2014;371:2309-2319. Kraut JA, Madias NE. Serum anion gap: its uses and limitations in clinical medicine. Clin J Am Soc Nephrol. 2007;2:162-174. Laski ME, Sabatini S. Metabolic alkalosis, bedside and bench. Semin Nephrol. 2006;26:404-421.

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239

CHAP TER

Acute Kidney Injury Ajay K. Singh, MBBS, MBA, FRCP Anika T. Singh Jameela Kari, MD

Key Clinical Questions 1

How is acute kidney injury de ined?

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What are the major causes o acute kidney injury?

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How is acute kidney injury diagnosed and managed?

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What role does renal replacement therapy, such as hemodialysis, have in acute kidney injury?

INTRODUCTION Acute kidney injury (AKI) is de ned as a potentially reversible sudden deterioration in renal unction due to prerenal, intrarenal, or postrenal causes. AKI is requently accompanied by dysregulation o extracellular uid volume and electrolytes, and a marked increase in the retention o nitrogenous and nonnitrogenous waste products over a period o hours to weeks. AKI may be oliguric (< 400 mL/d) or nonoliguric (> 400 mL/d). AKI can also be de ned as an acute and sustained increase in serum creatinine o 0.5 mg/dL (44.2 µmol/L), i the baseline is less than 2.5 mg/dL (221 mmol/L), or an increase in serum creatinine more than 20% i the baseline is more than 2.5 mg/dL (221 mmol/L). There have been several attempts to achieve consensus among intensivists and nephrologists on the de nition o AKI. The Acute Dialysis Quality Initiative (ADQI) group published the RIFLE classi cation o AKI in 2004 based on three severity categories (risk, injury, and ailure) and two clinical outcome categories (loss and end-stage renal disease) (Table 239-1). The parameters assessed in the RIFLE classi cation are changes in serum creatinine level, glomerular ltration rate (GFR), or urine output (UO). The baseline serum creatinine level and GFR may not be readily available. Hence the consensus committee recommends the use o the Modi cation o Diet in Renal Disease (MDRD) equation to estimate GFR/1.73 m 2. The proportional decrease in GFR is calculated rom 75 mL/min per 1.73 m 2, the agreed-upon lower limit o normal. (The RIFLE criteria or adults have been adapted in children and are termed the pRIFLE criteria.) A modi ed RIFLE criteria schema has been proposed by the Acute Kidney Injury Network (AKIN). The AKIN diagnostic criteria (Table 239-2) and the classi cation/staging system (Table 239-3) or AKI are an abrupt (within 48 hours) reduction in kidney unction currently de ned as an absolute increase in serum creatinine o more than or equal to 0.3 mg/dL (≥ 26.4 µmol/L), a percentage increase in serum creatinine o more than or equal to 50% (1.5- old rom baseline), or a reduction in urine output (documented oliguria o less than 0.5 mL/kg/h or more than 6 hours). The absolute increase in the serum creatinine levels (≥ 0.3 mg/dL) in this diagnostic criterion is based on epidemiologic data demonstrating that changes in serum creatinine levels o 0.3 to 0.5 mg/dL are associated with increased mortality risk. Also, the timeline o within 48 hours is deliberately included in the diagnostic criteria because o data demonstrating poorer outcomes within this period. The clinical utility and universal adoption o either RIFLE or AKIN criteria remain uncertain, and uture studies are needed to demonstrate their validity. EPIDEMIOLOGY

■ AKI IN THE HOSPITALIZED PATIENT AKI is a complication o up to 18% o all hospital admissions in the United States. Major causes o hospital-acquired AKI include volume depletion resulting in decreased renal per usion, major surgery, septic shock, congestive cardiac ailure, contrast nephropathy, and aminoglycoside antibiotics. Acute tubular necrosis (ATN) is identi ed as the most requent clinicopathologic entity in hospital-acquired AKI, ollowed by prerenal azotemia, acute-onset chronic renal ailure, and urinary tract obstruction.

■ AKI IN THE CRITICALLY ILL PATIENT AKI occurs in 25% or more o patients admitted to critical care units, with major causes including sepsis, multiorgan ailure, 1952

■ COMMUNITY-ACQUIRED AKI Community-acquired AKI accounts or 1% o the hospital admissions in the United States. Community-acquired AKI in developed nations mainly a ects older patients, with causes including acute tubular necrosis, prerenal azotemia, acute-onset chronic renal ailure, and obstructive uropathy. In developing countries, AKI is predominantly a disease o in ants and children and is due to prerenal etiologies, such as dehydration rom acute diarrheal illness. Falciparum malaria, HIV/AIDS, obstetrical mishaps, dengue ever, snake bites, insect stings, botanical and chemical nephrotoxins, acute glomerulonephritis, hemolytic uremic syndrome, and alternative medical therapies are important etiological actors o AKI in the tropics. Crush injury rom natural disasters such as earthquake contributes to regional epidemics o AKI.

■ AKI AMONG CHILDREN Recent studies indicate that the incidence o AKI in pediatric patients is increasing. This may be related to the high rates o AKI in hospitalized children in the setting o cardiac surgery and stem cell transplantation.

■ CAUSES OF AKI The causes o AKI can be classi ed under three broad categories: prerenal, renal, and postrenal (Table 239-4). Prerenal azotemia and ischemic ATN account or 75% o AKI.

■ PRERENAL CAUSES Prerenal causes are characterized by a reversible loss o kidney unction and a drop in GFR due to decreased renal per usion, while the integrity o renal structural components is maintained. Prerenal causes account or approximately 70% o community-acquired AKI and 40% o hospital-acquired cases. Prerenal azotemia is typically

TABLE 239-2 AKIN Diagnostic Criteria for AKI An abrupt (within 48 hours) reduction in kidney unction currently de ined as an absolute increase in serum creatinine o more than or equal to 0.3 mg/dL (≥ 26.4 µmol/L), a percentage increase in serum creatinine o more than or equal to 50% (1.5- old rom baseline), or a reduction in urine output (documented oliguria o less than 0.5 mL/kg/h or more than 6 h).

C H A P T E R 2 3 9 A c u t e K i d n e

Less than 0.3 mL/kg/h or 24 h or anuria or 12 h

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hypotension, nephrotoxin administration, and prerenal actors. AKI a ects mostly older patients who have chronic morbidities or are severely ill on admission to the hospital. The overall in-hospital mortality rate in intensive care unit (ICU)-associated AKI is approximately 60%.

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Urine Output Criteria Less than 0.5 mL/kg/h or more than 6 h

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in GFR by 25%, or UO < 0.5 mL/kg/h or 6 h Injury (I)—Increase in serum creatinine level × 2.0 or decrease in GFR by 50%, or UO < 0.5 mL/kg/h or 12 h Failure (F)—Increase in serum creatinine level × 3.0, decrease in GFR by 75%, or serum creatinine level > 4 mg/dL with acute increase o > 0.5 mg/dL; UO < 0.3 mL/kg/h or 24 h, or anuria or 12 h Loss (L)—Persistent AKI, complete loss o kidney unction > 4 wk End-stage kidney disease (E)—Loss o kidney unction > 3 mo

Stage 1

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• Risk (R)—Increase in serum creatinine level × 1.5 or decrease

TABLE 239-3 AKIN Classification/Staging System for AKI

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TABLE 239-1 RIFLE Classification for AKI

Note: This classi ication is modi ied rom RIFLE (Risk, Injury, Failure, Loss, and End-stage kidney disease) criteria. The staging system proposed is a highly sensitive interim staging system and is based on recent data indicating that a small change in serum creatinine in luences outcome. Only one criterion (creatinine or urine output) has to be ul illed to quali y or a stage. * 200%-300% increase = 2-3- old increase. † Given wide variation in indications and timing o initiation o renal replacement therapy (RRT), individuals who receive RRT are considered to have met the criteria or stage 3 irrespective o the stage they are in at the time o RRT.

due to decreased e ective circulating volume, true hypovolemia, or impaired renal per usion. Decreased ef ective circulating volume may be due to cardiac ailure, aortic stenosis, nephrotic syndrome, cirrhosis, hepatorenal syndrome, acute pancreatitis, cardiac tamponade, sepsis, or systemic vasodilatation in conjunction with sepsis or anesthesia. Intravascular volume depletion, a possible result o dehydration due to vomiting, diarrhea, poor uid intake, ever, and diaphoresis, is the most common cause o prerenal azotemia in the outpatient setting. Excessive urination (polyuria) due to excess diuretics, diabetes insipidus, or poorly controlled diabetes mellitus can also cause AKI. Other causes o volume depletion include gastrointestinal bleeding and plasma loss due to burns, trauma, and anaphylaxis. Decreased renal per usion may result rom renal artery stenosis or renal vein thrombosis, or more o ten rom drugs such as nonsteroidal anti-in ammatory drugs (NSAIDs). NSAIDs inter ere with glomerular autoregulation, especially in patients above the age o 60 with additional risk actors or prerenal azotemia, such as atherosclerotic vascular disease, preexisting CKD, hypotension, diuretic use, cirrhosis, nephrotic syndrome, and congestive cardiac ailure. Immunosuppressive drugs, such as tacrolimus and cyclosporine, lead to acute kidney injury by inducing vasoconstriction o the a erent and e erent glomerular arterioles o the kidneys. Angiotensinconverting enzyme (ACE) inhibitors may cause AKI in patients with unilateral or bilateral renal artery stenosis.

■ INTRARENAL CAUSES Intrarenal causes o AKI are characterized by the loss o kidney unction due to structural damages to glomeruli, tubules, vessels, or interstitium. They are o ten categorized based on the primary site o renal injury. 1953

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TABLE 239-4 Causes of AKI Prerenal Intravascular volume depletion: diarrhea, vomiting, hemorrhage, poor luid intake, sepsis, overdiuresis Decreased e ective circulating volume to the kidneys: congestive cardiac ailure, nephrotic syndrome, cirrhosis, or hepatorenal syndrome Renal hypoper usion due to exogenous agents: ACE inhibitors, NSAIDs Renal Acute tubular necrosis: ischemia Toxins: drugs (eg, aminoglycosides), contrast agents, pigments (myoglobin or hemoglobin); heavy metals Glomerular disease: rapidly progressive glomerulonephritis, systemic lupus erythematosus, small-vessel vasculitis (Wegener granulomatosis or polyarteritis nodosa), Henoch-Schönlein purpura (IgA nephropathy), Goodpasture syndrome Acute proli erative glomerulonephritis: endocarditis, poststreptococcal in ection Vascular disease Microvascular disease: atheroembolic disease (cholesterolplaque microembolism), thrombotic thrombocytopenic purpura, hemolytic uremic syndrome, HELLP syndrome (hemolysis, elevated liver enzymes and low platelets) Macrovascular disease: renal artery occlusion, abdominal aortic aneurysm Interstitial disease: allergic reaction to drugs, autoimmune disease, systemic lupus erythematosus, mixed connective tissue disease, pyelonephritis, in iltrative disease (lymphoma or leukemia) Postrenal Benign prostatic hypertrophy or prostate cancer, cervical cancer, retroperitoneal disorders, intratubular obstruction (stones, urate crystals, myeloma light chains), pelvic mass or invasive pelvic malignancy, intraluminal bladder mass (clot, tumor or ungal ball), neurogenic bladder, urethral strictures

Acute tubular necrosis (ATN) is the most common cause o intrinsic renal ailure, and is also the most common cause o hospitalacquired acute kidney injury. It usually results rom tubular ischemia and in ammation, as in sepsis and shock, or tubular toxins such as heme pigments (such as myoglobin rom rhabdomyolysis or hemoglobin rom intravascular hemolysis), cisplatin, ethylene glycol, and myeloma light chains. Ischemic tubular necrosis may occur in patients with sustained prerenal azotemia. I os amide, a chemotherapeutic agent, is known to cause acute tubular dys unction in the proximal tubule. Hospital-acquired ATN is o ten multi actorial. For example, it may occur in a septic patient exposed to a potentially nephrotoxic drug, such as an aminoglycoside or amphotericin, or a ter the administration o a radiocontrast agent in a hypovolemic patient with preexisting renal dys unction. Patients with severe renal ischemia may develop cortical necrosis with injury to both tubules and glomeruli. Causes include severe sepsis, dehydration, snake bites, obstetrical catastrophes, thrombotic microangiopathies, and malaria. The prognosis or recovery is less avorable than or ATN. Glomerular disease in the orm o rapidly progressive glomerulonephritis (RPGN) and acute proli erative glomerulonephritis may cause AKI. RPGN may be primary or secondary in origin, the latter 1954

being associated with systemic diseases like systemic lupus erythematosus, Wegener granulomatosis, polyarteritis nodosa, HenochSchönlein purpura, and Goodpasture syndrome. RPGN can also progress to end-stage renal disease (ESRD) in days to weeks. Acute proli erative glomerulonephritis occurs in patients with bacterial endocarditis, poststreptococcal in ection, and postpneumococcal in ection. Vascular disease (ie, microvascular and macrovascular renal arterial disease) can cause AKI. Thrombotic thrombocytopenic purpura, hemolytic uremic syndrome, HELLP syndrome (hemolytic anemia, elevated liver enzymes, low platelet count), glomerular capillary thrombosis, and atheroembolic disease may all cause AKI. Patients undergoing interventional or invasive procedures involving the major vessels and those with arrhythmias are at an increased risk or AKI rom atheroemboli. Interstitial disease, such as acute interstitial nephritis (AIN), o ten results rom an allergic reaction to an o ending agent (Tab le 239-5). Withdrawal o the o ending agent requently results in reversal o AKI. AIN may also occur in systemic in lammatory conditions such as sarcoidosis, systemic lupus erythematosus (SLE), Legionnaires' disease, and hantavirus in ection.

■ POSTRENAL CAUSES Postrenal AKI is characterized by loss o kidney unction due to intrinsic or extrinsic masses obstructing the urinary collecting system, rom the tip o the papillae to the urethral meatus. The most common causes are prostatic hypertrophy or carcinoma, cervical cancer, and other causes o bladder neck obstruction. Less common causes include bilateral renal stones, bladder carcinoma,

TABLE 239-5 Drugs Associated with Acute Interstitial Nephritis Beta-lactam antibiotics • Methicillin • Ampicillin • Oxacillin • Penicillin • Na cillin • Cephalosporins Other antibiotics • Sul onamides • Ri ampin • Polymyxin • Ethambutol • Tetracycline • Vancomycin • Erythromycin • Cipro loxacin • Acyclovir • Indinavir • Alpha-inter eron Diuretics • Thiazides • Furosemide • Chlorthalidone • Triamterene

NSAIDs • Fenopro en • Indomethacin • Naproxen • Ibupro en • Tolmetin • Di lunisal • Piroxicam • Ketopro en • Diclo enac Other drugs • Proton-pump inhibitors • Diphenylhydantoin • Cimetidine • Sul inpyrazone • Allopurinol • Aspirin • Carbamazepine • Phenindione • Clo ibrate • Phenylpropanolamine • Aldomet • Phenobarbital • Azathioprine • Diazepam • Captopril • Cisplatin

■ HISTORY AND PHYSICAL EXAMINATION

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Figure 239-1 depicts the interaction o hemodynamic, immunological, and in ammatory actors in mediating AKI.

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PATHOPHYSIOLOGY

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nonspeci c symptoms o azotemia, such as anorexia, nausea, vomiting, malaise, atigue, pruritus, metallic taste in the mouth, and dyspnea. Bone pain may suggest multiple myeloma. The patient's daily uid intake and output, daily weights, inpatient and outpatient medications, including NSAIDs and other over-the-counter medications, and outpatient laboratory data should be reviewed. Recent radiology studies should be assessed to determine i the patient has a history o recent contrast use in angiography or computed tomographic (CT) imaging. On physical examination, patients should be assessed or signs o volume overload, such as peripheral edema, pulmonary rales, and elevated neck veins. Physical ndings o advanced renal ailure

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De cre a s e in sys te mic blood pre s s ure

Tubula r injury a nd dys function

Activa tion of ne uroha rmona l me cha nis ms

Affe re nt a rte riola r cons triction

Contra ction of me s a ngia l pe ricyte s

Re duce d glome rula r pre s s ure a nd pla s ma flow

↓ Pe rfus ion of glome rula r ca pilla ry loops

↓ GFR

↓ S urfa ce a re a for GF a nd ↓ Kf

Impa ire d Na Cl re a bs orption

Tubula r block

Ba ckle a k of glome rula r filtra te

TG fe e dba ck a ctiva tion

↓ GFR

De cline in e ffe ctive GFR

↓ GFR

Intrins ic o r Extrins ic Luminal Obs truc tio n

Incre a s e d ure te ra l pre s s ure

Va s odila tory pros ta gla ndins P GE 2 a nd P Gl2 come in re s cue to ma inta in GFR

Incre a s e d leve ls of thromba xa ne A2 in prolonge d obs truction a nd PAF, ma cropha ge de rive d products

Intra re na l va s ocons triction

↓ GFR

GFR, Glome rula r filtra tion ra te, GF, Glome rula r filtra tion; Kf, Ultra filtra tion coe fficie nt; PAF, P la te le t a ctiva ting fa ctor; Na Cl, S odium chloride ; TG, Tubuloglome rula r

Figure 239 1 Pathophysiology o AKI. 1955

1. Prerenal AKI

2. Intrinsic AKI Diseases o the large renal vessels

Diseases o small vessels and glomeruli

Acute tubular necrosis

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TABLE 239-6 List of Clinical Features and Diagnostic Clues

Tubulointerstitial disease

3. Post renal AKI

Absolute or postural hypotension Low jugular venous pressure Dry mucus membranes (dehydration) Decreased e ective circulatory volume (eg, heart ailure or liver disease) Flank or abdominal pain (renal artery thrombosis) Retinal plaques, palpable purpura, livedo reticularis (atheroembolic disease) Flank pain (renal vein thrombosis) New cardiac murmur (post-in ectious glomerulonephritis), skin rash or ulcers, arthralgias (lupus), sinusitis (anti-GBM disease), lung hemorrhage (anti-GBM, ANCA-associated vasculitis, lupus) Fever, neurologic abnormalities (HUS-TTP) Headache, papilledema, heart ailure with LVH (malignant hypertension) Postictal state, trauma or prolonged immobilization (rhabdomyolysis) Fever, trans usion reaction (hemolysis) Bone pain, atigue, malaise in individuals > 60 years (multiple myeloma) History o alcohol abuse, altered mental status (ethylene glycol ingestion) Fever, rash, arthralgias (allergic interstitial nephritis) Fever, lank pain, tenderness (acute bilateral pyelonephritis) Palpable bladder, lank, or abdominal pain

include asterixis, myoclonus, and pericardial or pleural rubs. A minority o patients with acute interstitial nephritis have ever and rash. Muscle pain, bluish discoloration o the toes, livedo reticularis, and loss o oot or ankle pulses suggest atheroembolic renal ailure. Palpable purpura, mononeuritis multiplex, hemoptysis, or prominent upper respiratory tract symptoms, such as sinusitis or otitis, suggests glomerulonephritis associated with systemic vasculitis. Other clinical clues or the diagnosis o AKI are listed in Table 239-6.

Figure 239 2 Dysmorphic red blood cells in urine: a common inding in glomerulonephritis. (Courtesy o Dr. Richard Dion.) nor speci c or this condition, as it may be seen in pyelonephritis, prostatitis, glomerulonephritis, atheroembolism, and transplant rejection. In ethylene glycol ingestion, double-pyramid, ovoid, or dumbbell-shaped oxalate crystals are usually present in the urine. Amber-colored rhomboid uric acid crystals may be ound in urine in tumor lysis syndrome. Urine indices help to di erentiate prerenal azotemia rom ATN. The ractional excretion o sodium (FENa) is the percentage o sodium ltered by the glomeruli that is excreted in the urine. Patients that are volume depleted are sodium-avid and have a low FENa. It is calculated as ollows: FENa =

[Urine Na × Plasma Creatinine] × 100 Plasma Na × [Urine creatinine]

In prerenal azotemia, urine osmolality is usually > 500 mOsm/kg, the urinary sodium concentration is < 20 mmol/L, and the ractional excretion o sodium (FENa) is < 1%, whereas in tubular necrosis and urinary obstruction the urine osmolality is < 350 mOsm/kg, the urine sodium concentration is > 40 mmol/L, and the FENa is > 1% (in ATN, the FENa is usually, but not always, > 2%). There are exceptions: the FENa may be < 1% in acute tubular injury due to radiocontrast exposure or heme pigment, and also in acute glomerulonephritis. In early urinary tract obstruction, the urinary sodium concentration and FENa can be low. The FENa is also not reliable in the setting o chronic kidney disease, where a high FENa may be seen in patients with prerenal

■ URINE EVALUATION A urine specimen should be collected or dipstick, microscopic sediment analysis, culture, and urine chemistries, including sodium, protein, creatinine, and osmolality. Heme-positive urine with ew erythrocytes on microscopy suggests myoglobinuria or hemoglobinuria, as in rhabdomyolysis and trans usion reactions. Proteinuria and hematuria suggest glomerular injury. Microscopic evaluation o the urine sediment is crucial. The presence o dysmorphic red cells (Figure 239-2) and red cell casts (Figure 239-3) should raise the possibility o glomerulonephritis. The presence o at either deposited in epithelial cells (oval at bodies), in casts ( atty casts) or ree at suggests nephrotic syndrome. The presence o white cells and white cell casts suggests tubulointerstitial in ammation or a pyelonephritis. Hyaline casts and granular casts are suggestive o prerenal azotemia (Figures 239-4 and Figure 239-5). The presence o epithelial cells and pigmented granular casts (muddy brown casts) suggests acute tubular necrosis (ATN) (Figure 239-6). Eosinophiluria, once thought to be diagnostic o AIN, is neither sensitive 1956

Figure 239 3 Red blood cell cast: a common urine microscopic inding in glomerulonephritis. (Courtesy o Dr. Richard Dion.)

C H A P T E R 2 3 9 A c u t e K i

PRACTICE POINT

•

The ractional excretion o sodium (FENa) aids in di erentiating prerenal azotemia rom acute tubular necrosis. However, in patients who have recently received diuretics, sodium excretion is enhanced, and the FENa is not reliable. In this setting, the ractional excretion o urea (FEUrea) may be help ul as urea excretion is not enhanced by diuretics. It is calculated as ollows: FEUrea =

•

[Urine urea × Plasma creatinine] = 100 [Plasma urea × Urine creatinine]

Normally, the FEUrea is 50% to 65%, while in prerenal azotemia, it is usually less than 35%. Patients with metabolic alkalosis and prerenal azotemia have a alsely elevated FENa, because o bicarbonaturia with obligate losses o sodium in urine. In these patients, the ractional excretion o chloride (FECl) may be used instead: FECl =

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[Urine Cl × Plasma creatinine] × 100 [Plasma Cl × Urine creatinine]

A FECl < 1% is consistent with prerenal azotemia.

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azotemia, especially early in the clinical course. Typical urine ndings in di erent causes o AKI are listed in Table 239-7.

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Figure 239 4 Hyaline cast: a common inding in prerenal acute kidney injury; may also be seen in normal individuals with concentrated urine. (Courtesy o Dr. Richard Dion.)

Figure 239 5 Granular cast with a waxy margin: a common inding in prerenal azotemia and acute tubular necrosis. (Courtesy o Dr. Richard Dion.)

■ EVALUATION FOR OBSTRUCTION Urinary tract obstruction should be excluded in patients presenting with AKI. Renal ultrasonography is the pre erred imaging technique, with a sensitivity o 80% to 85% and a speci city approaching 100% or the diagnosis o obstruction. Ultrasonography also helps to identi y kidney stones and kidney size. To locate the exact site o obstruction and correct it, percutaneous anterograde urography (via percutaneous puncture o the renal pelvis under uoroscopy) and retrograde urography (via cystoscopy and ureteral catheterization) may be necessary. In patients with retroperitoneal brosis, obstruction o the urinary tract may be dif cult to visualize by sonography, and computed tomography or magnetic resonance imaging may be necessary. Bladder catheterization can be use ul in ruling out urethral obstruction.

■ RENAL BIOPSY IN AKI Percutaneous renal biopsy has a limited role in the immediate evaluation and treatment o AKI. However, it is valuable in diagnosing primary renal diseases, such as glomerulonephritis and AIN, a ter prerenal and postrenal causes o AKI have been excluded. Renal biopsy also plays a role in the evaluation o early allogra t dys unction in renal transplant patients, and in management decisions related to subsequent use o immunosuppressive therapy.

■ NOVEL BIOMARKERS OF AKI The de nition o AKI is still based on a rise in serum creatinine and all in urine volume and GFR. However, serum creatinine is not an

■ BLOOD TESTS Serum blood urea nitrogen (BUN), creatinine, electrolytes, calcium, phosphorous, and albumin should be obtained in all patients. Serum creatinine concentration typically rises by 1 to 1.5 mg/dL daily when there is a marked decrement in kidney unction. Most hospital laboratories are now able to calculate glomerular ltration (estimated GFR or eGFR) using an equation. Other use ul blood tests include uric acid, creatinine kinase, serum immunoelectrophoresis, serum osmolal gap, and complete blood count with di erential. In malignancies, serum urate and calcium levels are o ten high. Eosinophilia suggests allergic interstitial nephritis. Elevated serum creatine kinase is present in rhabdomyolysis. Abnormal serum electrophoresis is present in multiple myeloma. In alcohol ingestions such as ethylene glycol or methanol, there is high osmolal gap.

Figure 239 6 Urine microscopy, showing muddy brown casts o acute tubular necrosis (ATN). (Courtesy o Dr. Serban Nicolescu.) 1957

Condition Prerenal azotemia Intrarenal azotemia Tubular injury ischemia Nephrotoxins Acute interstitial nephritis Acute glomerulonephritis Postrenal azotemia

Dipstick Test Trace or no proteinuria

Sediment Analysis A ew hyaline casts possible

Mild-to-moderate proteinuria Mild-to-moderate proteinuria Mild-to-moderate proteinuria; hemoglobin; leukocytes Moderate-to-severe proteinuria; hemoglobin Trace or no proteinuria; can have hemoglobin, leukocytes

Pigmented granular casts Pigmented granular casts White cells and white-cell casts; eosinophils; red cells Red cells and red-cell casts; red cells can be dysmorphic Crystals, red cells, and white cells possible

Urine Osmolality mOsm/kg > 500

Fractional Excretion of Sodium 1 >1 >1

> 500

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TABLE 239-7 Urine Findings in AKI

optimal marker o renal unction as it is in uenced by age, sex, race, diet, exercise, and lean muscle mass. Moreover, secretion o creatinine may account or 10% to 40% o its excretion, potentially masking a drop in GFR. The development o sensitive and speci c new biomarkers o renal unction and injury has been an area o intense research. Serum cystatin C, a cysteine protease inhibitor produced by all nucleated human cells and reely ltered into the glomerulus, appears to be a more accurate marker o renal unction and a more robust predictor o all-cause mortality in elderly persons than serum creatinine. Potential urinary biomarkers o early AKI are under investigation, such as kidney injury molecule-1, shed by proximal tubular cells a ter ischemic or nephrotoxic damage; interleukin-18, generated in the proximal tubule in AKI; osteopontin, a cytokine involved in kidney in ammation and repair; and the cytoprotective protein clusterin, a atty-acid-binding protein, and neutrophil-gelatinase-associated lipocalin, which are overexpressed by tubular cells undergoing injury and oxidative stress. However, their precise role in the diagnosis and management o AKI has yet to be de ned. MANAGEMENT OF AKI The management o AKI is directed at identi ying and treating the underlying cause and preventing and treating complications. This may involve reversal o hemodynamic instability, elimination o nephrotoxins and avoidance o additional insults, and correction o electrolyte disturbances, uremia, and acid-base disorders. Maintenance o euvolemic status is central to the management o ischemic acute renal ailure. Assessment and correction o volume status are based on care ul physical examination, and at times by invasive monitoring. Composition o the uid replaced should match that o the uid lost. Minor to moderate hemorrhagic loss is treated with normal saline (0.9% NaCl), whereas severe blood loss is best managed by trans using packed red blood cells. Repletion o uid is usually done with normal saline in hypovolemic patients; however, most patients with AKI have volume overload. Distinguishing true hypovolemic AKI rom hepatorenal syndrome (HRS) is a challenge in patients with cirrhosis and ascites. A gentle uid challenge should be per ormed in these patients, with slow administration o uids titrated to jugular venous pressure or central venous/pulmonary artery pressure. In true hypovolemia, urine output increases and the serum creatinine alls, whereas in HRS, a uid challenge is usually ine ective. In patients with AKI and volume overload, loop diuretics such as urosemide, dosed between 20 and 100 mg, should be administered as an intravenous bolus, initially every 6 hours. The dose can be increased i an adequate response

1958

is not achieved. I bolus dosing o urosemide is ine ective, a continuous in usion o urosemide may be initiated, although evidence or its ef cacy compared to intermittent diuretic dosing is limited. When oliguria or anuria persists despite conservative management, dialysis is indicated. Treatment o intrarenal AKI depends on the underlying pathology. Immunosuppressive agents, including steroids and cytotoxic drugs, may be bene cial in treating acute glomerulonephritis or vasculitis. Angiotensin-converting enzyme (ACE) inhibitors are help ul in treating AKI associated with hypertension and scleroderma renal crisis, but should generally be avoided in patients with hemodynamically related kidney injury. AKI due to malignant hypertension should be treated by vigorous control o blood pressure. Possible culprit drugs should be stopped in patients with possible AIN. While the role o corticosteroids in the management o AIN remains unclear since no randomized, controlled trials have been per ormed, and retrospective studies have shown con icting results, most clinicians treat patients with a 1- to 2-week course o high dose steroids (prednisone 60 mg/d, rapidly tapered over a 1-2-week period). Obstruction o the urethra or bladder neck can be relieved temporarily by insertion o a transurethral or suprapubic catheter. Obstructive lesions o the ureter are treated by stenting, either by anterograde percutaneous or retrograde cystoscopic placement. Patients o ten undergo a postobstructive diuresis or several days ollowing relie o the obstruction, and care should be taken to avoid dehydration. Transient salt wasting syndrome occurs in approximately 5% o patients, and requires administration o intravenous normal saline to maintain blood pressure. The most common electrolyte disturbance in AKI is hyperkalemia. Initial treatment should include calcium gluconate i the potassium level is > 6 mEq/L, or i electrocardiographic changes are present. Potassium may be transiently shi ted into cells with intravenous insulin (10 units) and glucose (25 g) as a bolus in usion. As acidosis avors hyperkalemia by promoting extracellular movement o potassium, intravenous sodium bicarbonate (three ampules in 1 L o 5% dextrose) leads to translocation o potassium into cells and may also acilitate renal potassium excretion. Treatment with sodium bicarbonate is less e ective acutely. Sodium polystyrene sul onate (Kayexalate) given orally (25-50 g mixed with 100 mL o 20% sorbitol) or as enema (50 g in 50 mL o 70% sorbitol and 150 mL o tap water) is a more de nitive therapy that leads to excretion o potassium rom the body. Kayexalate enemas with 70% sorbitol are rarely associated with colonic necrosis, especially in critically ill patients, and should be avoided i other therapeutic options are available. More recently sodium zirconium cyclosilicate (ZS-9) and patiromer sorbitex calcium have been shown to be e ective in treating

RENAL REPLACEMENT THERAPY (RRT) IN AKI Dialysis as a treatment modality in AKI is most use ul in the elimination o metabolic wastes and uremic toxins, but it is also e ective in the maintenance o uid, electrolyte, and acid-base status. There is limited consensus among nephrologists regarding choice o dialysis, timing o initiation, requency and intensity o dialysis, and impact on patient outcomes, due to lack o de nitive evidence rom studies conducted thus ar in the setting o AKI (Table 239-8).

■ CONTINUOUS RENAL REPLACEMENT THERAPY VERSUS HEMODIALYSIS In critically ill patients, continuous renal replacement therapy (CRRT) is now a popular and requently pre erred alternative to intermittent hemodialysis, especially in hemodynamically unstable patients. CRRT can be either arteriovenous or venovenous, such as continuous arteriovenous hemodialysis (CAVHD) and continuous venovenous hemodialysis (CVVHD). CVVHD is pre erred over CAVHD

Peritoneal dialysis (PD) is generally not a avored therapeutic modality or AKI. However, it is the pre erred mode o renal replacement therapy in resource-limited settings and the developing world. Advantages include easy portability and access placement, better hemodynamic stability among patients, and the avoidance o systemic anticoagulation and its associated complications. Disadvantages include the risk o injury to the viscera during catheter placement, low levels o solute clearance, metabolic instability in critically ill patients, and the high risk o peritonitis.

C H A P T E R 2 3 9 A c u t e K i d n e y j u r

■ PERITONEAL DIALYSIS

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because o the high ultra ltration rate, predictable blood ow rate, avoidance o arterial puncture, ease o vascular access (either emoral or internal jugular vein, via a double lumen catheter), and reduced risk o heparin-induced bleeding. Compared to intermittent dialysis, CRRT has several advantages, including lower risk o hemodynamic instability, ease o administration o nutritional support, and more accurate control o uid and metabolic status. Disadvantages include prolonged anticoagulation, nursing burden, cost, and limited mobility. Sustained low-e iciency dialysis (SLED) or extended daily dialysis (EDD) is another increasingly popular dialytic modality o choice or critically ill patients and has the bene its o both continuous and intermittent dialysis methods. The advantages o SLED are good hemodynamic tolerability, high clearance levels o even small solutes, convenient treatment schedules, and cost e ectiveness.

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hyperkalemia. ZS-9 is an a nonabsorbable cation trap that selectively binds K+ in exchange or H+ and Na+; it binds K+ immediately upon ingestion. In contrast, patiromer is a nonabsorbable polymer that enhances K+ excretion by the exchange o Ca2+, predominantly in the distal colon. Dialysis remains an important option i hyperkalemia is severe or is re ractory to treatment. Acidosis may be corrected by administering sodium bicarbonate when the pH level is less than 7.2, or the serum bicarbonate level is less than 15 mEq/L. Bicarbonate may be administered orally (a 300 mg tablet contains 3.6 mEq o sodium bicarbonate) or intravenously. Ampules or intravenous administration are provided as 7.5% sodium bicarbonate (44.6 mEq/50 mL) or 8.4% sodium bicarbonate (50 mEq/50 mL). The required bicarbonate dose is measured by the ollowing equation: bicarbonate de cit (mEq) = (lean body weight, LBW) (0.5) (desired HCO3 – actual HCO3). I acidosis cannot be corrected, dialysis is per ormed. Diet plays an important role in patients with AKI who become nutritionally de cient. The daily caloric intake should be 30 to 45 kcal (126-189 kJ) per kg per day. In nondialysis patients, protein intake should be restricted to 0.6 g/kg/d. Patients receiving dialysis should have 1 to 1.5 kg/d.

■ DIALYSIS-RELATED COMPLICATIONS Dialysis-induced complications include hypotension and complement cascade activation during the blood-dialyzer interaction. Hypotension worsens existing AKI because o impaired renal autoregulatory mechanisms. The upregulation o neutrophil adhesion molecules due to blood-dialyzer membrane interaction result in urther damage to renal tissues. Unlike cuprophane, biocompatible membranes like polymethylmethacrylate or polyacrylonitrile do not activate complement to any great extent, and the use o biocompatible membranes is associated with improved recovery o renal unction and reduced mortality among AKI patients requiring dialysis.

■ PROGNOSIS TABLE 239-8 Renal Replacement Therapy in AKI • Re ractory hypervolemia, hyperkalemia (K+ > 6.5 mEq/L),

•

• • •

• •

acidosis (pH < 7.1), azotemia (BUN > 100 mg/dL), uremic signs, and severe dysnatremias (Na+ > 155 mEq/L or < 120 mEq/L) are absolute indications or dialysis Hemodialysis (HD) is more e ective than peritoneal dialysis (PD) in the management o AKI because solute clearance and control o metabolic abnormalities are usually better in HD Hemodialysis can be intermittent dialysis, slow low-e iciency dialysis (SLED), or continuous renal replacement therapy (CRRT) In patients with hemodynamic instability, SLED or CRRT is recommended over HD Peritoneal dialysis (PD) is use ul when hemodialysis is unavailable or vascular access cannot be obtained and is the mainstay o treatment in resource-limited settings. The major disadvantages are risk o peritonitis and visceral injury during catheter placement The optimal timing or the initiation o dialysis is still unclear The dialytic modality o choice depends on the availability o resources in the health care institute, technical expertise o the clinicians, and the clinical status o the patient

The mortality rate o AKI ranges rom 20% to 50%, and up to 70% in the ICU and surgical setting. Advanced age, severe underlying disease, preexisting poor nutritional status, and multisystem organ ailure are associated with increased mortality. About 10% to 20% who su er AKI will require maintenance dialysis. In ection, cardiorespiratory complications, and underlying disease states are the major causes o death in patients with AKI, rather than AKI itsel . The availability o health care in a given country greatly in uences the prognosis or AKI.

■ CONSULTATION Nephrology consultation is appropriate in AKI when the cause is unclear a ter initial testing has been per ormed; i assistance is required with assessment and management o volume status; i intrinsic renal disease, such as glomerulonephritis or AIN, is suspected, and renal biopsy may be needed or diagnosis; and i an indication or dialysis is present, such as re ractory uid overload, severe metabolic acidosis, hyperkalemia, pericarditis, mental status changes, or overdose with a dialyzable toxin or drug.

■ DISCHARGE CHECKLIST • Has close outpatient ollow-up been arranged, with clinical assess-

ment and measurement o serum creatinine and electrolytes? 1959

may worsen renal unction, such as NSAIDs? • Have drug doses been adjusted or estimated GFR? • I the patient seems likely to need dialysis in the near uture, have they been told to avoid phlebotomy and intravenous placement in one arm to preserve it or gra t or stula creation?

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• Has the patient been warned to avoid dehydration and drugs that

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SUGGESTED READINGS

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Anderson S, Eldadah B, Halter JB, et al. Acute kidney injury in older adults. J Am Soc Nephrol. 2011;22:28-38.

Molitoris BA, Levin A, Warnock DG, et al. Improving outcomes rom acute kidney injury. J Am Soc Nephrol. 2007;18:1992-1994. Pakula AM, Skinner RA. Acute kidney injury in the critically ill patient. J Intensive Care Med. Epub ahead o print, 2015 Mar 9. Pisoni R, Wille KM, Tolwani AJ. The epidemiology o severe acute kidney injury: rom BEST to PICARD. Nephron Clin Pract. 2008;109(4):c188-c191. Stavros F, Yang A, Leon A, Nuttall M, Rasmussen HS. Characterization o structure and unction o ZS-9, a K+ selective ion trap. PLoS One. 2014;9:e114686.

Himmel arb J, Ikizler TA. Acute kidney injury: changing lexicography, de nitions, and epidemiology. Kidney Int. 2007;71:971-976.

Waikar SS, Liu KD, Chertow GM. Diagnosis, epidemiology and outcomes o acute kidney injury. Clin J Am Soc Nephrol. 2008;3:844-861.

La rance JP, Miller DR. Acute kidney injury associates with increased long-term mortality. J Am Soc Nephrol. 2010;21:345-352.

Weir MR, Bakris GL, Pitt B. New agents or hyperkalemia. N Engl J Med. 2015;372:1570-1571.

McCullough PA, Costanzo MR, Silver M, Spinowitz B, Zhang J, Lepor NE. Novel agents or the prevention and management o hyperkalemia. Rev Cardiovasc Med. 2015;16:140-155.

240

CHAP TER

Calcium Disorders Elizabeth H. Holt, MD, PhD John P. Bilezikian, MD

INTRODUCTION Abnormalities o calcium metabolism are common in hospital practice. Hypercalcemia has a prevalence o 0.1% in the general population and 1% among hospitalized patients. In the inpatient setting, hypercalcemia o ten portends serious illness, especially malignancy. Hypocalcemia is also common in the hospital, especially in patients with chronic renal ailure or sepsis. Hypocalcemia may also be a mani estation o vitamin D de ciency, which has a prevalence o up to 80% on specialized geriatric inpatient units. CALCIUM METABOLISM Precise regulation o calcium homeostasis is essential because o the critical role o calcium in many physiological activities. It is the major mineral o bone. It also plays major roles in neuronal transmission, muscle contraction, and blood coagulation. Calcium is also required or the proper unctioning o many enzymes, endocrine secretory processes, and biochemical signaling pathways.

■ NORMAL SERUM CALCIUM LEVELS

Key Clinical Questions 1

How is serum calcium regulated?

2

What are the causes o hypercalcemia in hospitalized patients?

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How is hypercalcemia diagnosed and managed?

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What causes hypocalcemia in hospitalized patients? How is it diagnosed and managed?

A typical laboratory range or serum total calcium concentration is between 8.4 and 10.2 mg/dL. Approximately hal o this total amount is bound to albumin, with the remainder in ree (ionized) orm. The normal ree calcium concentration range is 4.5 to 5.3 mg/dL. A small raction (10%) o circulating calcium is complexed with anions, such as citrate and phosphate.

■ REGULATION OF CALCIUM HOMEOSTASIS The three organ systems that together regulate serum calcium are the gastrointestinal tract, kidneys, and skeleton. The two principal regulatory hormones are parathyroid hormone (PTH) and 1,25-dihydroxyvitamin D3. PTH is a peptide secreted rom the parathyroid glands in its active ull-length con guration, known as PTH(1-84). Its plasma hal -li e is very short, on the order o 3 to 5 minutes. The major regulator o PTH secretion is the ree calcium concentration in extracellular uid. Elevated levels o ree or ionized calcium promptly block secretion o PTH, while reduced serum calcium levels promptly increase secretion o PTH. 1,25-dihydroxyvitamin D3 is produced by a sequence o activation steps (Figure 240-1), starting with the generation o cholecalci erol (vitamin D3) through exposure o skin to ultraviolet light o a specied wavelength (90-315 nm). Cholecalci erol or its plant analogue, ergocalci erol (vitamin D2), can also be obtained by dietary sources or in nutritional supplements. Cholecalci erol or ergocalci erol is converted in the liver to a hydroxylated orm, 25-hydroxyvitamin D3 or 25-hydroxyvitamin D2. The 25-hydroxylated orms o vitamin D are converted to their active orms by a second hydroxylation step in the kidney leading to 1,25-dihydroxyvitamin D2 or D3. Both dihydroxylated orms o vitamin D are active in human subjects, although there is controversy over whether vitamin D3 is more potent than vitamin D2. PTH maintains serum calcium concentrations by conserving calcium that has been ltered at the kidney glomerulus and by mobilizing calcium rom bone. 1,25-dihydroxyvitamin D maintains serum calcium by acilitating absorption o calcium rom the gastrointestinal tract and, like PTH, mobilizing calcium rom bone. Under normal conditions, the calcium absorbed by the gut (approximately 150-200 mg/d) is matched by the calcium eliminated by the kidney. At the dynamic skeletal inter ace, as much as 1961

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LABORATORY MEASUREMENT OF BLOOD CALCIUM 7-De hydrochole s te rol

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The measurement o serum calcium may be help ul when a disturbance o calcium metabolism is suspected. However, in many disorders o calcium metabolism, such as osteoporosis or Paget disease o bone, the serum calcium concentration is typically normal. Serum

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25-hydroxyvitamin D to 1,25-dihydroxyvitamin D (Figure 240-2). When PTH levels are elevated (ie, primary hyperparathyroidism), 1,25-dihydroxyvitamin D levels increase. When PTH levels are low (ie, hypoparathyroidism), 1,25-dihydroxyvitamin D levels are typically low. The three organ systems (bone, gastrointestinal tract, and kidneys) and the two calcium-regulating hormones (PTH and 1,25-dihydroxyvitamin D) work together to maintain normal calcium homeostasis. When they are not perturbed by disease or by the aging process, they are an exquisitely sensitive and e ective servomechanism.

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– 25(OH) D3

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P i a nd othe r fa ctors

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Figure 240 1 Vitamin D synthesis and activation. Vitamin D is synthesized in the skin in response to ultraviolet radiation and is also absorbed from the diet. It is then transported to the liver, where it undergoes 25-hydroxylation. This metabolite is the major circulating form of vitamin D. The final step in hormone activation, 1-hydroxylation, occurs in the kidney. (Reproduced, with permission, rom Fauci AS, Braunwald E, Kasper DL, et al. Harrison’s Principles of Internal Medicine, 17th ed. New York, NY: McGraw-Hill; 2008, Fig. 346-4.)

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500 mg o calcium is turned over daily. This process is in a steady state, with net calcium neither gained nor lost. Thus, under normal circumstances, there are no signi cant uctuations in body calcium stores, nor is there any major change in circulating serum calcium concentrations. Changes in ree or ionized calcium concentration are registered virtually instantly by parathyroid cells via the calcium-sensing receptor (CaSR). This receptor is located on the parathyroid cell sur ace, where its extracellular domain senses binding o calcium ions. I the circulating calcium concentration rises, the Ca2+-CaSRcomplex leads to a rise in intracellular calcium, inhibiting both PTH secretion and synthesis. I the serum calcium concentration alls, the Ca2+-CaSR complex sends a reduced signal to the cell, leading to an increase in PTH secretion and synthesis. 1,25-dihydroxyvitamin D decreases PTH production, although not as power ully as does the ionized calcium signal. There is a stronger interaction between levels o 25-hydroxyvitamin D and PTH. They have an inverse relationship, with PTH levels rising when 25-hydroxyvitamin D levels all below approximately 25 to 30 ng/mL. In turn, increased PTH stimulates the 1-alpha hydroxylase enzyme in the kidney that converts

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Figure 240 2 Schematic representation of the hormonal control loop for vitamin D metabolism and function. A reduction in the serum calcium below 2.2 mmol/L (8.8 mg/dL) increases secretion of parathyroid hormone (PTH), mobilizing additional calcium from bone. PTH promotes the synthesis of 1,25(OH)2D in the kidney, which, in turn, stimulates the mobilization of calcium from bone and intestine, and regulates the synthesis of PTH by negative feedback. (Reproduced, with permission, rom Fauci AS, Braunwald E, Kasper DL, et al. Harrison’s Principles of Internal Medicine, 17th ed. New York, NY: McGraw-Hill; 2008, Fig. 346-5.)

Many individuals with mild hypercalcemia (serum calcium level < 11 mg/dL) are asymptomatic, although some may report mild atigue, vague changes in cognitive unction, depression, or constipation.

C H A P T E R 2 4 0 C a l c i u m D i e r

■ PRESENTING SYMPTOMS AND HISTORY

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Signs and symptoms o hypercalcemia may be absent or subtle, except when calcium is signi cantly elevated or has increased rapidly. The diagnostic workup o hypercalcemia is usually straightorward (Figure 240-3) because two causes, primary hyperparathyroidism and malignancy-associated hypercalcemia, account or approximately 90% o cases. In addition, most individuals with primary hyperparathyroidism are asymptomatic and discovered on routine biochemical screening tests, while most individuals with malignancy-associated hypercalcemia have a known advanced malignancy at the time that hypercalcemia occurs. I the malignancy is not known, it is generally quickly apparent. When neither o these two etiologies is readily apparent, identi cation o the other potential etiologies requires a comprehensive history, physical examination, laboratory tests, and, occasionally, diagnostic imaging studies.

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HYPERCALCEMIA

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measurements may be per ormed by spectrophotometry or by atomic absorption spectrophotometry, with the latter yielding more accurate measurements. Spuriously high readings may occur i the tourniquet is in place too long be ore blood is drawn and hemoconcentration occurs. Under these circumstances, the measured serum calcium value can rise by as much as 0.4 mg/dL. On the other hand, the sample can read alsely low i the blood sample is obtained rom a central, high- ow site via a central venous catheter. For most clinical situations, the total serum calcium is measured. This may need to be corrected or the circulating albumin concentration. For every 1 g/dL reduction in the serum albumin, the total calcium is adjusted upward by 0.8 mg/dL. This may be calculated as ollows:Corrected total calcium = measured total calcium + 0.8 (4.0 – serum albumin) In theory, ree or ionized serum calcium is a more accurate physiological measurement than the adjusted total serum calcium concentration, but the sampling technique (the blood has to be ree- owing and not impeded by a tourniquet) and strict anaerobic collection conditions are problematic. Moreover, the measuring instrument has to be in regular use and properly calibrated. Samples have to be measured immediately. These technical issues somewhat limit the clinical utility o the ionized calcium measurement.

Rule out s purious la b re s ult, me dica tions , re na l ins ufficie ncy, immobiliza tion

Me a s ure s imulta ne ous ca lcium a nd P TH

P TH e le va te d or ina ppropria te ly norma l

P TH low

Che ck 24-hour urine ca lcium e xcre tion

Norma l or e le va te d 24 hour urine ca lcium e xcre tion

P rima ry hype rpa ra thyroidis m

Low 24 hour urine ca lcium e xcre tion

FHH

Ma ligna ncy

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Che ck P THrP , 1,25-(OH)2 vita min D, othe r pote ntia l me dia tors (IL-1)

Che ck 1,25-(OH)2 vita min D, othe r e ndocrine dis orde rs ,s upple me nts , drugs , occult ma ligna ncy

Ele va te d

Low

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Loca l os te olytic hype rca lce mia

Figure 240 3 Diagnostic approach to hypercalcemia. FHH, familial hypocalciuric hypercalcemia; PTH, parathyroid hormone; PTHrP, parathyroid hormone-related protein. *Alow 24-hour urinary calcium does not necessarily rule out primary hyperparathyroidism. 1963

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Symptomatic mani estations o hypercalcemia are more apparent when the serum calcium concentration is between 12 and 14 mg/dL. These symptoms include anorexia, nausea, weakness, and depressed mental status. As hypercalcemia may induce polyuria and nephrogenic diabetes insipidus, dehydration may occur should the compensatory polydipsia not keep up with urinary water losses. When serum calcium levels rise above 14 mg/dL, pro ound dehydration, renal dys unction, and central nervous system changes, such as progressive lethargy, disorientation, and coma, may develop. In addition to the absolute magnitude o the serum calcium elevation, the rate o increase in serum calcium also in uences symptoms. Individuals who are chronically hypercalcemic may have relatively ew symptoms, even with serum calcium values up to 15 to 16 mg/dL. In contrast, those whose calcium level has risen abruptly may have symptoms at much more modest calcium levels. Elderly or debilitated patients are more likely to be a ected by hypercalcemia than younger individuals. The medical record may contain clues to etiology. Prescription medications (Table 240-1), oods, and vitamin and nutritional supplements should be reviewed. A care ul amily history might uncover a amilial endocrine condition. A history o amily members with endocrine tumors o the pituitary or pancreas suggests multiple endocrine neoplasia type 1 syndrome (MEN-1). A amily history o pheochromocytoma or medullary thyroid cancer is consistent with MEN-2 syndrome. Patients with sarcoidosis may have a history o unexplained ever, lymphadenopathy, skin rashes, or pulmonary symptoms. Bone pain suggests myeloma or other malignancies, although it may also be a nonspeci c nding o hypercalcemia.

■ THE PHYSICAL EXAMINATION The physical examination is directed at identi ying signs o hypercalcemia. Evidence o dehydration such as orthostasis or dry mucous membranes may be present, although hypercalcemia must be marked and prolonged or these physical ndings to be appreciated. The physical examination is o ten normal in patients with hypercalcemia, especially i calcium levels are only modestly elevated. Rarely, severe and prolonged hypercalcemia may produce a visible horizontal deposit o calcium salts on the cornea, a nding called band keratopathy. E ort should be made to identi y signs o common causes o hypercalcemia, such as malignancy and primary hyperparathyroidism. The physical examination in primary hyperparathyroidism, like most hypercalcemic states, is usually not noteworthy. A mass is virtually never ound in the neck, because enlarged parathyroid glands are still too small to be elt. However, when the serum calcium is markedly elevated, a neck mass may signi y a parathyroid carcinoma. Symptomatic kidney stones might be accompanied by costovertebral tenderness. Enlarged lymph nodes suggest sarcoid, lymphoma, or metastatic carcinoma.

■ DIAGNOSIS Laboratory studies The rst step in evaluating hypercalcemia is adjustment or serum albumin. I the corrected serum calcium is elevated, it should be repeated. Renal unction should also be assessed, because hypercalcemia may develop or worsen in the setting o acute renal ailure. I hypercalcemia is con rmed, the next step is measurement o serum PTH. The PTH level is the most important test or distinguishing between the two most common causes o hypercalcemia, primary hyperparathyroidism and malignancy-associated hypercalcemia (Table 240-1). The so-called intact immunochemiluminometric assay or PTH assay primarily measures the intact molecule, PTH(184), as well as a large circulating ragment that is oreshortened at the amino terminus, PTH(7-84). A more speci c assay that measures 1964

only PTH(1-84), the bio-intact assay, is also available, but it has not shown any clear advantages over the older assay, which has been in clinical use or over 20 years. When the creatinine clearance alls below 60 mL/min, these assays may begin to show elevations in PTH due to the accumulation o inactive ragments, and also perhaps due to increased secretory activity o the parathyroids (secondary hyperparathyroidism). When the parathyroid glands are unctioning normally, hypercalcemia should suppress PTH levels. Hypercalcemia is said to be

TABLE 240-1 Causes of Hypercalcemia PTH mediated

PTH independent

Primary hyperparathyroidism Parathyroid adenoma Parathyroid hyperplasia Parathyroid carcinoma Tertiary hyperparathyroidism Familial hypocalciuric hypocalcemia Lithium Thiazide diuretics HHM: PTHrP mediated Squamous carcinoma o the lung, oropharynx, nasopharynx, larynx, and esophagus Gynecologic (cervical, ovarian) Urologic (renal, transitional cell o bladder) Pheochromocytoma Pancreatic islet cell tumors T-cell lymphoma Others HHM: 1,25-(OH)2-D3 mediated B-cell lymphoma Local osteolytic hypercalcemia Multiple myeloma Breast carcinoma metastatic to bone Lymphoma Others Medications/supplements Vitamin D Vitamin A Thiazide diuretics Calcium-containing antacids (in milk-alkali syndrome) Granulomatous diseases Sarcoidosis Tuberculosis Histoplasmosis Leprosy Other conditions Factitious hypercalcemia (due to increased plasma protein levels) Acute renal ailure Severe thyrotoxicosis Adrenal insu iciency Immobilization

HHM, humoral hypercalcemia o malignancy; PTH, parathyroid hormone; PTHrP, parathyroid hormone-related protein.

Additional tests The electrocardiogram may show a shorted QTc interval, particularly i hypercalcemia has occurred over a short period o time. Bone mineral density (BMD) by dual energy x-ray absorptiometry (DXA) may be help ul. In primary hyperparathyroidism, there is a typical pattern o BMD with relative preservation o cancellous bone, as in the lumbar spine, and signi cant loss o cortical bone, as in the emoral neck and distal third o the radius. Abdominal imaging studies (CT or ultrasound) may identi y renal stones or nephrocalcinosis. Serum and urine protein electrophoresis should be obtained i myeloma is suspected. Skeletal radiographs may reveal lytic lesions o multiple myeloma or other malignancies. In primary hyperparathyroidism, skeletal radiographs may show subperiosteal bone resorption or brown tumors o bone, but are rarely needed or diagnosis.

■ CAUSES OF PTH-MEDIATED HYPERCALCEMIA Primary hyperparathyroidism Elevation o both serum calcium and PTH concentrations, in the absence o lithium use or low urinary calcium excretion as seen in amilial hypocalciuric hypercalcemia, supports a diagnosis o primary hyperparathyroidism. In this condition, PTH levels are usually within 1.5 to 2.0 times above the upper limit o normal. Extremely high levels o PTH raise the specter o parathyroid carcinoma. Typical primary hyperparathyroidism is associated with mild hypercalcemia, within 1 mg/dL above the upper limit o normal. The PTH level may be elevated, but may also all in the upper portion o the normal range, which is inappropriate in hypercalcemia. Normocalcemic primary hyperparathyroidism is a new diagnostic entity applied to patients whose total and ree serum calcium levels are normal, but in whom the PTH level is consistently elevated. In the absence o a secondary cause or elevated PTH levels, it is elt that these individuals have an early orm o primary hyperparathyroidism.

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Primary hyperparathyroidism is the most common cause o hypercalcemia in outpatients. The incidence is estimated to be approximately 21.6 per 100,000 person-years. The mean age at diagnosis is in the sixth decade o li e, and there is a emale-to-male ratio o 2:1. The clinical mani estations depend largely on the severity o the hypercalcemia. When primary hyperparathyroidism was rst described more than 80 years ago, most patients presented with advanced disease with overt radiographic abnormalities o bone (osteitis brosa cystica) and kidneys (nephrolithasis or nephrocalcinosis). Since the introduction more than 40 years ago o automated multichannel autoanalyzers or measuring serum chemistry, primary hyperparathyroidism is most o ten diagnosed by routine blood testing, well be ore the development o other signs or any symptoms. It also may be uncovered during the evaluation o osteoporosis or during the workup o renal stone disease. The most common clinical presentation today is mild asymptomatic hypercalcemia. In 75% to 80% o cases, a solitary, benign parathyroid adenoma is present. Hyperplasia involving multiple parathyroid glands is ound in 15% to 20% o cases, and parathyroid carcinoma is present in less than 0.5%. On occasion, double adenomas are ound. Patients with MEN-1 or MEN-2 usually have parathyroid hyperplasia involving all parathyroid glands. Parathyroid surgery is always indicated in symptomatic primary hyperparathyroidism, unless there are medical contraindications. The role o parathyroid surgery in asymptomatic primary hyperparathyroidism is more controversial. According to the guidelines o the Fourth International Workshop on the Management o Asymptomatic Primary Hyperparathyroidism, indications or surgery in asymptomatic patients include a serum calcium > 1 mg/dL above the upper limit o normal; creatinine clearance < 60 mL/min; 24-hour urine calcium > 400 mg/d and increased stone risk by biochemical stone risk analysis; presence o nephrolithiasis or nephrocalcinosis by x-ray, ultrasound or CT; T-score < –2.5 at lumbar spine, hip, or distal third o the radius; vertebral racture by x-ray, CT, MRI or VFA; and age < 50. Patients who do not meet these guidelines can be ollowed expectantly. Thiazide diuretics and lithium should be avoided. Dietary calcium should not be restricted, because such restriction may promote urther elevation o PTH, and possibly have adverse e ects on bone mass. In patients who are vitamin D de cient, cautious replacement o vitamin D is advised. Patients should maintain hydration. Bisphosphonates increase lumbar spine BMD in primary hyperparathyroidism, without a major e ect on the serum calcium concentration. The calcimimetic agent, cinacalcet, reduces serum calcium in primary hyperparathyroidism without having a major e ect on BMD. Cinacalcet is indicated or use in patients with parathyroid cancer, as well as patients with primary hyperparathyroidism who are unable to undergo parathyroidectomy. Alendronate has not been approved by the Food and Drug Administration (FDA) or use in primary hyperparathyroidism. Lithium can change the set point or the calcium-sensing receptor on the parathyroid gland, such that a higher serum calcium concentration is needed to inhibit PTH secretion. This can lead to mild biochemical abnormalities, such as high levels o calcium and high-normal to elevated PTH levels, that mimic primary hyperparathyroidism, but do not require medical intervention. Thiazide-associated hypercalcemia also occurs. Many patients with hypercalcemia on thiazides probably have primary hyperparathyroidism. When thiazide therapy is discontinued, the hypercalcemia o ten persists, and the diagnosis o primary hyperparathyroidism is made.

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PTH-mediated i serum calcium is elevated, and the PTH level is high or inappropriately normal. In this latter situation, one is usually dealing with primary hyperparathyroidism, although amilial hypocalciuric hypercalcemia (FHH) and medication-induced hypercalcemia, as rom thiazide diuretics or lithium, can also be associated with elevated PTH levels. When PTH levels are appropriately suppressed in hypercalcemia, the di erential diagnosis includes malignancy, granulomatous disease, medications, milk-alkali syndrome, thyrotoxicosis, and adrenal insuf ciency. Other recommended tests in the evaluation o hypercalcemia include serum electrolytes and 25-hydroxyvitamin D. Levels o 25-hydroxyvitamin D typically exceed 150 ng/mL in vitamin D toxicity due to excess intake. Levels this high cannot be achieved by sun exposure alone. High 1,25-(OH)2D levels may be seen in any granulomatous disease, particularly sarcoidosis or certain lymphomas. Inorganic phosphorus measurement may be help ul, as a low-normal serum phosphate is o ten seen in primary hyperparathyroidism, while high phosphate may be seen in vitamin D intoxication. An elevated serum creatinine may indicate dehydration or true renal dys unction due to renal deposition o calcium salts or other causes. An elevated alkaline phosphatase level suggests elevated bone turnover. This may be con rmed by measuring bone-speci c alkaline phosphatase or other indices o bone turnover, such as serum osteocalcin, serum C-terminal collagen peptide measurement, or urinary N-terminal collagen peptide. Most orms o hypercalcemia are accompanied by hypercalciuria (24-hour urine calcium excretion > 4 mg/kg/24 hours). However, in primary hyperparathyroidism, renal calcium excretion is lower than expected or the degree o hypercalcemia, because PTH conserves ltered calcium in the distal renal tubule.

Familial hypocalciuric hypercalcemia Familial hypocalciuric hypercalcemia, also known as benign amilial hypercalcemia, is a rare genetic condition caused by inactivating mutations in the CaSR. This results in lack o sensitivity o the 1965

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parathyroid cell to ambient serum calcium, a higher set point or the extracellular ionized calcium concentration, and inappropriately normal to mildly elevated PTH levels. Patients with FHH have chronic asymptomatic hypercalcemia, with very low urinary calcium excretion. The relatively low urinary calcium excretion in FHH helps distinguish it rom primary hyperparathyroidism, although low urinary calcium excretion may also occur in individuals with primary hyperparathyroidism. A amily history o asymptomatic mild hypercalcemia, especially in individuals younger than 40 years, is suggestive o FHH. Other supportive evidence or FHH includes a very low urinary calcium to creatinine clearance ratio (< 0.01), and a history o amily members who have undergone noncurative parathyroidectomy or presumed primary hyperparathyroidism. When FHH is suspected, urther evaluation is necessary, such as screening o other amily members or hypercalcemia. Genetic testing or FHH may be appropriate, as it may otherwise be exceedingly dif cult to distinguish FHH rom primary hyperparathyroidism. Tertiary hyperparathyroidism Conditions associated with low serum calcium are usually also associated with chronically elevated PTH levels, which is an appropriate physiological response. This is called secondary hyperparathyroidism. The rise in PTH may restore the serum calcium to normal, or calcium may remain low or in the low-normal range. Secondary hyperparathyroidism is not a hypercalcemic state. Common causes o secondary hyperparathyroidism include vitamin D de ciency, intestinal malabsorption o calcium or vitamin D, renal-based hypercalciuria, severe nutritional calcium de ciency, and especially chronic renal insuf ciency. Correction o the underlying cause usually returns serum PTH concentrations to normal. Normalization o PTH may be relatively rapid, i the cause is o recent onset, or it may be protracted, i the associated condition has been longstanding. In patients with prolonged secondary hyperparathyroidism, the reactive state can become semiautonomous, leading to hypercalcemia. This condition, known as tertiary hyperparathyroidism, is most o ten seen in patients with poorly controlled chronic kidney disease. Tertiary hyperparathyroidism is usually associated with hyperplasia o multiple glands, but may also be caused by a parathyroid adenoma rom a single clone o parathyroid cells. Further investigations Most patients with primary hyperparathyroidism have a serum calcium concentration below 11 mg/dL. Serum phosphate tends to be in the low-normal range (2.5-3.2 mg/dL). Rarely, a nonanion gap hyperchloremic acidosis rom a PTH-induced de ect in bicarbonate resorption may be seen. Urinary calcium excretion tends to be in the upper range o normal. However, hypercalciuria in primary hyperparathyroidism does not always predispose to renal stones, despite the act that hypercalciuria is a risk actor or kidney stones in euparathyroid subjects. Bone turnover markers tend to be at the upper limit or normal, but occasionally can be rankly elevated. Once the diagnosis o primary hyperparathyroidism is made, it should be determined whether or not the patient meets clinical criteria or parathyroidectomy (Table 240-2). I the clinical situation is appropriate, consideration should be given to the possibility o one o the MEN syndromes, particularly i the patient is young, or has a personal or amily history o a related endocrinopathy. A diagnosis o MEN-1 or MEN-2 should prompt a search or multiple parathyroid gland disease.

■ CAUSES OF PTH-INDEPENDENT HYPERCALCEMIA I the serum calcium concentration is elevated but the PTH level is appropriately suppressed, the patient has hypercalcemia due to causes other than hyperparathyroidism (PTH-independent hypercalcemia). 1966

TABLE 240-2 Indications for Parathyroidectomy in Primary Hyperparathyroidism Fragility racture at any site Serum calcium > 1.0 mg/dL above upper limit o normal On bone mineral density by DXA: T-score < - 2.5 at lumbar spine, total hip, emoral neck or distal 1/3 radius (use o Z-scores instead o T-scores is recommended or measurement o BMD in premenopausal women and men younger than 50 years o age). Vertebral racture by x-ray, CT, MRI, or Vertebral Fracture Assessment (VFA) Creatinine clearance < 60 cc/min 24-h urine or calcium > 400 mg/d and increased stone risk by biochemical stone risk analysis Presence o nephrolithiasis or nephrocalcinosis clinically or by x-ray, ultrasound or CT Age < 50 Surgery is also indicated in individuals where medical monitoring is not desired or possible, or or those selecting surgery, without meeting any guidelines, i there are no medical contraindications. Source: Adapted rom Bilezikian JP, et al. Guidelines or management o asymptomatic primary hyperparathyroidism: Summary statement rom the ourth international workshop. J Clin Endocrinol Metab. 2014;99:3561-3569.

Cancer is the most common cause. Other causes include thyrotoxicosis, vitamin D intoxication, sarcoidosis, immobilization, Addison disease, and various drugs and supplements. In hypercalcemia o malignancy, calcium is usually moderately or severely elevated, and PTH is low or undetectable. Signi cant dehydration and generalized debility are usually evident, along with other cancer-related symptoms. Usually, the diagnosis o malignancy has already been established when patients become hypercalcemic. Hypercalcemia o malignancy has two orms: humoral hypercalcemia o malignancy (HHM) and local osteolytic hypercalcemia. HHM results rom tumor production o a circulating actor with systemic e ects on calcium metabolism, acting on skeletal calcium release, renal calcium handling, or intestinal calcium absorption. The usual cause o HHM is parathyroid hormone-related protein (PTHrP). Normally, PTHrP serves as a paracrine actor in tissues such as bone, skin, breast, uterus, placenta, and blood vessels, where it is involved in cellular calcium handling, smooth muscle contraction, and growth and development. The amino terminus o the PTHrP peptide is closely homologous with native PTH, and they share a common receptor. When PTHrP circulates at supraphysiologic concentrations, it produces e ects similar to PTH, activating osteoclasts to resorb bone, decreasing renal calcium output, and increasing renal phosphate clearance. Tumors that produce HHM by secreting PTHrP are typically squamous cell carcinomas o the lung, esophagus, head and neck, or cervix. Other tumors that may elaborate PTHrP include adenocarcinoma o the breast or ovary, renal carcinoma, transitional cell carcinoma o the bladder, islet cell tumors o the pancreas, T-cell lymphoma, and pheochromocytoma. As tumors that produce PTHrP do so in relatively small amounts, the syndrome typically develops in patients with a large tumor burden. It is there ore unusual or HHM to be the presenting eature o a cancer. The diagnosis may be con rmed by a commercially available radioimmunoassay or PTHrP. Care should be taken to ensure that blood or PTHrP levels is drawn and handled correctly to avoid spurious low results. Rarely, HHM is caused by the unregulated production o 1,25-dihyroxyvitamin D, usually by B-cell lymphomas, or other mediators that inter ere with calcium homeostasis.

PRACTICE POINT

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In the early 20th century, the Chicago physician Bertram Sippy gained celebrity because o his “Sippy diet” or peptic ulcers—a regimen o milk, cream, eggs, and cereal 3 times a day, punctuated by aggressive antacid therapy with hourly sodium bicarbonate and magnesium hydroxide. This may or may not have been curative or ulcers, but some patients certainly did develop severe hypercalcemia, in what became known as milk-alkali syndrome. Patients developed a metabolic alkalosis, which avors renal reabsorption o calcium, and the resulting hypercalcemia led to renal vasoconstriction, a all in GFR, and urther increases in serum calcium. Up to one-third o these patients had chronic renal ailure. Milk-alkali syndrome became rare with the introduction o H2-blockers and proton pump inhibitors or peptic ulcer disease.

C H A P T E R 2 4 0

A similar disorder is seen increasingly in postmenopausal women who consume large amounts o supplemental calcium carbonate and vitamin D or the prevention o osteoporosis. Pregnant or bulimic women with metabolic alkalosis rom emesis who are taking calcium and vitamin D are also at risk. It has been suggested that the disorder be renamed the calcium-alkali syndrome. Treatment is volume expansion with saline, cessation o alkali intake, and limitation o calcium supplementation.

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Hypercalcemia that requires urgent management is usually due to malignancy, rather than primary hyperparathyroidism. Urgent management includes aggressive rehydration, bisphosphonate therapy to decrease bone resorption, and elimination o contributing actors, such as calcium or vitamin D supplements, thiazide diuretic therapy, and immobilization. Second-line therapies include calcitonin to increase renal calcium excretion, and glucocorticoids to diminish intestinal calcium absorption.

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■ TREATMENT OF HYPERCALCEMIA

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The other major mechanism o malignancy-associated hypercalcemia is the direct invasion o bone by tumor, with lytic destruction and calcium release. While this was ormerly thought to be a mechanical process, it now appears to be driven by the local elaboration o cytokines leading to osteoclast-mediated bone resorption. In local osteolytic hypercalcemia, PTHrP and calcitriol are within normal limits. Bony metastases are usually obvious on imaging studies. The classic tumor associated with this syndrome is multiple myeloma, although breast cancer and certain lymphomas may also be responsible. Local osteolytic hypercalcemia may be perpetuated by a positive eedback loop. Factors produced by bone promote the growth and survival o metastases, and the tumor induces osteoclasts to produce actors promoting tumor growth, bone resorption, and hypercalcemia. Interruption o this positive eedback loop is the rationale or the use o bisphosphonates in the treatment o multiple myeloma. PTH-independent hypercalcemia also occurs in sarcoidosis, tuberculosis, and other granulomatous diseases. Macrophages in the granuloma convert 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D, via an unregulated 1-α hydroxylase enzyme. 25-hydroxyvitamin D levels are typically not elevated. When serum 25-hydroxyvitamin D levels are elevated, excessive vitamin D intake becomes the more likely etiology. Endocrine conditions that may occasionally lead to hypercalcemia include severe hyperthyroidism, which stimulates bone resorption, and Addison disease, where volume depletion reduces calcium clearance and control o calcium absorption is mitigated by glucocorticoid de ciency. Immobilization stimulates bone resorption and may increase serum calcium levels, particularly in bedbound hospitalized patients. This is usually seen in persons with high bone turnover, such as adolescents and patients with unrecognized hyperparathyroidism or Paget disease o bone. Drugs and dietary supplements may lead to hypercalcemia. Vitamin D intoxication and excessive intake o vitamin A, which activates bone resorption, are occasional culprits. Thiazide diuretics may cause hypercalcemia due to enhanced renal retention o calcium. In many cases, this develops in individuals with underlying mild primary hyperparathyroidism. In patients with an extensive negative workup, the rare possibility o occult malignancy should be considered, especially when PTHrP is elevated. Further imaging studies would then be needed or tumor localization, including a plain chest radiograph or a computed tomographic scan o the chest to rule out lung malignancy. I these are unrevealing, consideration should be given to otolaryngoscopic examination, esophagoscopy, or CT o the abdomen, ollowed by radiographic or endoscopic evaluation o the genitourinary tract i necessary.

Saline hydration Most patients with emergent hypercalcemia are dehydrated due to anorexia and polyuria. Intravascular volume should be aggressively restored with intravenous normal saline, with an initial bolus o 500 to 1000 mL, ollowed by maintenance uids at a rate o 200 mL/h or more, depending on the patient’s renal unction and cardiac reserve (Table 240-3). Typically, patients require 3 to 4 L or rehydration in the rst 24 hours. Patients need care ul monitoring o uid intake and output to prevent uid overload. Normal saline dilutes serum calcium, and acilitates calciuresis by increasing glomerular ltration rate and the amount o ltered calcium, and decreasing tubular calcium reabsorption. Administration o urosemide or other loop diuretics to urther promote calcium excretion may be considered a ter intravascular volume is restored. However, the use o loop

TABLE 240-3 Treatment of Hypercalcemia Intravenous fluids Normal saline Loop diuretic Furosemide intravenous (titrated to response, i necessary) Medications Bisphosphonates • Pamidronate (30-90 mg IV) • Zoledronic acid (4 mg IV) Calcitonin (4 IU/kg SC every 12 h) Prednisone (20-100 mg orally daily or equivalent)—in selected situations Plicamycin (15-25 µg/kg IV)—no longer used Gallium nitrate (200 mg/m 2/d in usion over 5 d)—no longer used Other interventions Decrease calcium and vitamin D intake (i causative) Maintain adequate oral hydration Primary therapy directed at tumor Chemotherapy Radiation Surgery

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Bisphosphonates The major target o medical management in severe hypercalcemia is osteoclast-mediated bone resorption. First-line therapy is an intravenous bisphosphonate, such as pamidronate or zoledronic acid. Pamidronate is administered in a dosage o 30 to 90 mg intravenously over several hours. Serum calcium levels should decline in 24 to 48 hours, although the maximal e ect may not be evident or several days. Zoledronic acid is given at a dosage o 4 mg intravenously, over no less than 15 minutes. It appears to have a greater potency and a longer duration o action than pamidronate. The need or repeat treatment with either pamidronate or zoledronic acid depends on the aggressiveness o the underlying malignancy. The rst dose o intravenous bisphophonates may be associated with ever, headache, arthralgias, and myalgias. Intravenous bisphosphonates should be used with caution in renal dys unction. Dose reduction o zoledronic acid is recommended or creatinine clearance below 60 mL/min, and use in patients with creatinine clearance below 30 mL/min is not recommended. Pamidronate may be used with caution in patients with renal insuf ciency, but the dose should be in used slowly, over 4 to 6 hours. The newer bisphophonate ibandronate may be associated with a lower risk o nephrotoxicity than other intravenous agents.

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Denosumab Denosumab is a RANKligand inhibitor that inter eres with osteoclast development and maturation. For hypercalcemia o malignancy, 120 mg subcutaneously is administered every 4 weeks, with additional 120 mg doses on days 8 and 15 o the rst month o therapy. Common side e ects include nausea and dyspnea. Denosumab is associated with osteonecrosis o the jaw, so a dental exam should be per ormed prior to therapy, and invasive dental procedures should be avoided during therapy. Atypical emur ractures occur rarely with denosumab. Other approaches to emergent hypercalcemia Intravenous bisphosphonates do not act immediately. I serum calcium needs to be reduced quickly, combined subcutaneous calcitonin (4 IU/kg every 12 hours) and intravenous bisphosphonate has become popular. Although rather weak, calcitonin acts rapidly, probably by acilitating urinary calcium excretion. The combination o a short-acting and long-acting anticalcemic can be very e ective. In severe or re ractory cases, hemodialysis against a low-calcium bath may be employed. Plicamycin and gallium nitrate are treatments o largely historical interest, either because o toxicity (plicamycin) or ine ectiveness (gallium nitrate). Glucocorticoids In myeloma, vitamin D intoxication, or disorders associated with ectopic production o 1,25-dihydroxyvitamin D, such as sarcoidosis and lymphoma, glucocorticoids can be very e ective. Glucocorticoids impair vitamin D action, inhibit intestinal calcium absorption, and may have a direct antitumor e ect. Addressing the underlying disorder Success ul management o acute hypercalcemia also requires treating the underlying etiology. When primary hyperparathyroidism is the cause, parathyroid surgery is indicated when the patient is stable enough to undergo the procedure. In malignancy-associated

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hypercalcemia, surgery, radiotherapy or chemotherapy may be appropriate. However, because hypercalcemia is o ten an end-stage complication o malignancy, such interventions may not be warranted.

■ DISCHARGE CHECKLIST: HYPERCALCEMIA

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diuretics to treat hypercalcemia has not been studied in randomized controlled trials, and may not be superior to vigorous use o saline alone. Thiazide diuretics should be avoided, as they enhance calcium reabsorption.

• Has outpatient ollow-up been arranged, with short-term repeat • •

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measurements o calcium, creatinine, and other electrolytes? Is there a long-range plan to prevent recurrent hypercalcemia, such as repeat bisphosphonate dosing? Have patients been instructed to seek prompt care i recurrent symptoms o hypercalcemia develop, such as nausea, vomiting, malaise, and polyuria? For patients with a new diagnosis o hypercalcemia o malignancy, have they been educated as to their underlying condition? Has outpatient oncology ollow-up been arranged? I hypercalcemia has arisen in the setting o advanced malignancy with poor prognosis, has hospice therapy been considered? HYPOCALCEMIA

Hypocalcemia is a serum calcium level which is below normal a ter correction or the albumin concentration. As with hypercalcemia, a ree (ionized) calcium determination on a correctly collected sample can be use ul to con rm hypocalcemia.

■ PRESENTING SYMPTOMS AND HISTORY Chronic hypocalcemia, unless severe, is usually asymptomatic. Signs and symptoms become more likely when albumin-adjusted serum calcium levels all below 7.5 to 8 mg/dL. These include numbness, paresthesias, and muscle spasms, and in severe cases, seizures and carpal, pedal, or laryngeal spasm. Important historical eatures include low dietary calcium and vitamin D intake, minimal sun exposure, gastrointestinal tract disease that may reduce vitamin D absorption, such as chronic pancreatitis, celiac disease, and in ammatory bowel disease, and alcohol, which decreases parathyroid hormone secretion both directly, and also indirectly, by causing magnesium depletion. A amily history o hypocalcemia suggests a genetic cause o hypoparathyroidism or an inherited abnormality o vitamin D metabolism. Prior neck surgery or neck irradiation may lead to hypoparathyroidism. A history o adrenal insuf ciency and mucocutaneous candidiasis suggests autoimmune polyendocrine syndrome type 1. Acute pancreatitis, rhabdomyolysis, and tumor lysis may lead to tissue precipitation o calcium, and massive blood trans usion may lead to intravascular precipitation o calcium with citrate.

■ PHYSICAL FINDINGS AND DIAGNOSTIC TESTING The physical examination is not sensitive or hypocalcemia. There may be a positive Chvostek sign (ipsilateral contraction o the acial muscles, induced by tapping on the acial nerve at a point about 1 cm below the zygomatic arch and 2 cm anterior to the earlobe). Trousseau sign may be elicited by in ating a blood pressure cu on the arm above systolic pressure or 3 minutes. It is considered positive i carpopedal spasm develops, with exion o the wrist, metacarpophalangeal joints, and thumb, and hyperextension o the ngers (Figure 240-4). Patients with these signs o neuromuscular irritability are at risk o rank tetany or seizures. QTc prolongation may be evident on the electrocardiogram. The serum calcium must be adjusted or albumin, as above, and a low value con rmed with a measurement o serum ionized calcium. Levels o phosphate, magnesium, creatinine, PTH, and 25-hydroxyvitamin D should be determined. 24-hour urinary calcium may be occasionally help ul. It is low in hypoparathyroidism and vitamin D de ciency, and high in patients with amilial

Figure 240 4 Position of fingers in carpal spasm due to hypocalcemic tetany. (Reproduced, with permission, rom Gardner DG, Shoback D. Greenspan’s Basic & Clinical Endocrinology, 8th ed. New York, NY: McGraw-Hill; 2007. Fig. 9-18.)

C H A E R 2 4 0 C a l c i u m D i s o r d e r

A ter con rming that calcium levels are truly low, exclusion o hypopa ra thyroidism by checking the level o PTH is central to the diagnostic workup o hypocalcemia (Figure 240-5). The most common causes o hypoparathyroidism are previous thyroid, parathyroid, or other neck surgery, and autoimmune destruction (Table 240-4). Autoimmune damage to the parathyroid glands may occur in isolated ashion, or in connection with ailure o other endocrine glands, such as premature ovarian ailure, hypothyroidism, and Addison disease, and mucocutaneous candidiasis. In ltration o the parathyroid glands, as may occur in hemochromatosis, Wilson disease, and metastatic cancer, can lead to hypoparathyroidism. Congenital absence o the parathyroid glands may be seen in DiGeorge syndrome. Functional hypoparathyroidism may result rom severe hypomagnesemia, because magnesium is necessary or both PTH release and PTH action. This is commonly seen in hospitalized alcoholic patients who are o ten markedly hypomagnesemic. The other major category o hypocalcemia includes conditions in which the parathyroid glands respond appropriately to hypocalcemia, and PTH is elevated. In vitamin D def ciency, serum calcium

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hypocalcemia with hypercalciuria, due to activating mutations in the calcium-sensing receptor. Genetic testing is available or some inherited disorders leading to hypocalcemia.

↓ Tota l s e rum ca lcium

Exclude obvious ca us e s of hypoca lce mia : • Chronic re na l ins ufficie ncy • Acute pa ncre a titis • Pos ts urgica l hypopa ra thyroidis m • Tis s ue bre a kdown (e g, crus h injury, ra pid tumor lys is )

Ionize d ca lcium

↓ Ionize d ca lcium

Norma l ionize d ca lcium

S e rum P TH

S e rum a lbumin to de re rmine [corre cte d tota l ca lcium = me a s ure d tota l ca lcium + 0.8 × (4–me a s ure d s e rum a lbumin)]

↓ P TH (hypopa ra thyroidis m)

P TH (a ppropria te ly e leva te d)

Figure 240 5 Diagnostic algorithm for hypocalcemia. (Reproduced, with permission, rom Nicoll D, McPhee SJ, Pignone M, et al. Pocket Guide to Diagnostic Tests, 5th ed. http://www.accessmedicine.com/pocketDiagnostic.aspx.) 1969

PTH deficiency or resistance

Vitamin D deficiency or resistance

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TABLE 240-4 Causes of Hypocalcemia

Iatrogenic

Miscellaneous conditions

Hypoparathyroidism Postsurgical Autoimmune polyendocrine syndromes Severe magnesium de iciency Congenital: DiGeorge syndrome In iltrative: hemochromatosis, thalassemia, Wilson disease PTH resistance Pseudohypoparathyroidism Nutritional deficiency Insu icient dietary intake o vitamin D Malabsorption Altered vitamin D metabolism Anticonvulsant medications (increased vitamin D metabolism) Renal ailure Vitamin D resistance Vitamin D pseudode iciency (VDDR I) Abnormal vitamin D receptor (VDDR II) Vitamin D-resistant hypophosphatemic rickets/osteomalacia Oncogenic osteomalacia Phosphate supplements Bisphosphonates (mainly seen with intravenous preparations in patients who are vitamin D de icient) Plicamycin Sepsis, critical illness Hypoalbuminemia ( actitious) Calcium malabsorption Hyperphosphatemia Acute pancreatitis Rhabdomyolysis Multiple trans usions o citrate-containing blood products Osteoblastic metastases (prostate or breast carcinoma)

PTH, parathyroid hormone.

concentrations may be low or in the low-normal range, because o compensatory increases in PTH, with secondary mobilization o skeletal calcium and reduction in renal calcium excretion. Clinical mani estations o vitamin D de ciency include osteomalacia, pathologic ractures, alls, and muscle weakness. Vitamin D de ciency has also been linked to autoimmune disease, cancer, and cardiovascular disease. Dietary vitamin D de ciency in the elderly is common, but o ten overlooked. Other adults at risk or vitamin D de ciency include darker complexion and low sun exposure. Recent reports suggest that vitamin D de ciency may be widely prevalent. Other causes o hypocalcemia include pseudohypoparathyroidism, a genetic disorder o PTH resistance associated with elevated parathyroid hormone levels, moon acies, short stature, and short ourth metacarpals. In acute pancreatitis, atty acids released through the action o pancreatic enzymes complex with calcium. Hypocalcemia due to the ormation o calcium phosphate complexes occurs in severe hyperphosphatemic states, such as renal ailure, 1970

rhabdomyolysis, and tumor lysis. Hypocalcemia may also be seen in patients given multiple red blood cell trans usions containing calcium chelators to prevent clotting. In patients with critical illness, hypocalcemia is probably multi actorial, arising as a consequence o the release o procalcitonin and other acute phase reactants, hypoalbuminemia, hypomagnesemia, and blunted PTH secretion.

■ TREATMENT OF HYPOCALCEMIA When hypocalcemia is severe and symptomatic, calcium gluconate should be administered by slow intravenous in usion. A typical calcium in usion is prepared with 10 ampules (100 mL) o 10% calcium gluconate (93 mg elemental calcium/ampule) in 1 L o D5W, administered at 50 mL/h. For an average-sized person, this is equivalent to 15 mg calcium/kg o body weight. Serum calcium should be tested requently, and the rate o in usion adjusted to maintain calcium levels in the low-normal range. De ciencies in magnesium or vitamin D should also be corrected. In severe cases, hypocalcemia may recur quickly a ter discontinuation o the calcium in usion, so oral calcium should be administered concurrent with tapering the in usion. In mild or moderate hypocalcemia, patients may be given oral calcium carbonate or calcium citrate, starting at 1000 to 1500 mg o elemental calcium daily in divided doses with meals. Patients should be instructed to take calcium with a protein meal, particularly patients with hypochlorhydria or achlorhydria, or who are on proton pump inhibitors. The protein meal supplies the acid that may be missing in these individuals, and which is required or the absorption o calcium carbonate. Calcium citrate does not require acid or absorption. I appropriate, vitamin D, in the orm o cholecalci erol (vitamin D3) or ergocalci erol (vitamin D2), should be provided. Recommended daily intake or vitamin D is currently being revised upward. The of cial recommendation or adults 50 years and older, 400 to 600 IU/d, is acknowledged by most experts to be inadequate. A popular approach to normalizing vitamin D levels in de cient individuals is to provide a weekly capsule o 50,000 IU or 8 to 12 weeks. This approach requires a prescription or ergocalci erol, because cholecalci erol is currently unavailable by prescription in the United States in this orm. Chronic hypoparathyroidism may require long-term administration o vitamin D and 1,25-dihydroxyvitamin D as needed to maintain normal levels. The goal o therapy is to maintain the serum calcium at a level at which the patient is asymptomatic. To avoid hypercalciuria, serum calcium levels are o ten maintained in the lower range o normal. Periodic monitoring or hypercalciuria and nephrocalcinosis in these patients may be appropriate. Hypoparathyroidism is the last classic endocrine de ciency disease or which the missing hormone is not available as an approved therapy. However, recent studies have shown promise in the use o recombinant parathyroid hormone (teriparatide) or hypoparathyroidism.

■ DISCHARGE CHECKLIST: HYPOCALCEMIA • Have repeat measurements o calcium, creatinine, and other elec-

trolytes been arranged within 1 to 2 weeks o hospital discharge? • Has outpatient endocrinology ollow-up been arranged or patients with hypoparathyroidism? HYPOPHOSPHATEMIA Hypophosphatemia is requent in hospitalized patients. It is most o ten caused by alcoholism, malnutrition, eating disorders, diabetic ketoacidosis, and re eeding o malnourished patients. It is also seen in burns, sepsis, trauma, in severe respiratory alkalosis, and as a complication o treatment with diuretics, some bisphosphonates, the antiretroviral drug teno ovir, sucral ate, and aluminum hydroxidecontaining antacids. In primary hyperparathyroidism, the serum phosphate has a tendency to be in the low-normal range, but rank hypophosphatemia is uncommon.

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Patel AM, Gold arb S. Got calcium? Welcome to the calcium-alkali syndrome. J Am Soc Nephrol. 2010;21:1440-1143.

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Holick MF. Vitamin D de ciency. N Engl J Med. 2007;357:266-281.

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Fraser WD. Hyperparathyroidism. Lancet. 2009;374(9684):145-158.

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Bilezikian, JP, Brandi ML, Eastell R, et al. Guidelines or the management o asymptomatic primary hyperparathyroidism: summary statement rom the Fourth International Workshop. J Clin Endocrinol Metab. 2014;99:3561-3569.

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Most patients with hyperphosphatemia have diminished renal excretion o phosphate, usually due to acute or chronic kidney disease. Hypoparathyroidism and pseudohypoparathyroidism are also classically associated with hyperphosphatemia. It can also be seen in acromegaly. Less o ten, hyperphosphatemia results rom transcellular phosphate shi ts, as in diabetic ketoacidosis (even despite total body phosphate depletion), or cellular injury, such as rhabdomyolysis, trauma, and tumor lysis syndrome. Patients may be asymptomatic, although symptoms o concomitant hypocalcemia and other electrolyte disturbances are o ten present. Vascular and

SUGGESTED READINGS

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HYPERPHOSPHATEMIA

so t tissue calci cation is common in hyperphosphatemic patients with chronic kidney disease, particularly i the calcium × phosphate product exceeds 55. Hyperphosphatemia is treated with phosphate binders and dietary phosphate restriction, as discussed in greater detail in Chapter 245.

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Symptoms o hypophosphatemia are unusual i the serum phosphate is > 2.0 mg/dL. Subjects with mild to moderate hypophosphatemia (serum phosphate between 1.5-2.0 mg/dL) may display muscle weakness, nausea, and vomiting, and anorexia. Those with severe hypophosphosphatemia (serum phosphate 5.0 mmol/L. Hyperkalemia can result rom redistribution, reduced K+ excretion, or increased K+ intake. Medications may lead to hyperkalemia by a ecting either potassium redistribution or excretion (Table 241-1). Pseudohyperkalemia is a laboratory arti act due to potassium release rom cells prior to laboratory measurement. It should be suspected when hyperkalemia is reported in the setting o red blood cell hemolysis, leukocytosis (> 70,000/mm 3) or thrombocytosis (> 500,000/mm 3), and no ECG changes are present. It 1972

has become less common with the increased use o plasma or potassium measurement, rather than serum. Plasma is the supernatant collected rom heparinized whole blood, whereas serum is the supernatant remaining a ter centri ugation o a clotted whole blood sample. Serum K+ is normally 0.3 mmol/L above the plasma K+, but may be higher i K+ is released rom the clot ormed in the tube. I pseudohyperkalemia is suspected, the plasma potassium should be measured instead o the serum potassium. Pseudohyperkalemia can also occur due to potassium release rom muscle cells ollowing prolonged constriction with a tourniquet or limb exercise while a tourniquet is in place.

Excessive intake o K+ rarely causes hyperkalemia in the setting o normal renal unction. Renal secretion o potassium is typically adequate at glomerular ltration rates (GFR) above 20 to 30 mL/min/1.73 m2. Patients with end-stage renal disease (ESRD) on hemodialysis usually tolerate a daily K+ intake o 2000 mg (51 mEq). Upregulated gut potassium excretion and shi ts in transcellular K+ prevent hyperkalemia between dialysis sessions. The loss o these mechanisms may result in the rapid development o hyperkalemia, especially with large exogenous loads o potassium, such as massive blood trans usions. Irradiation o blood and increased age o the blood increase the amount o ree potassium that is released during the blood trans usion. Seven-day-old blood has approximately 23 mmol/L o K+, while 42-day-old blood has approximately 50 mmol/L o K+.

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Excessive potassium intake

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ACE, angiotensin-converting enzyme; ARB, angiotensin receptor blocker; NSAIDs, nonsteroidal anti-in lammatory drugs.

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Spironolactone, eplerenone Triamterene, amiloride, Trimethoprim, pentamidine Digoxin, calcineurin inhibitors (cyclosporin, tacrolimus) Statins, cocaine Selected chemotherapy agents Succinylcholine

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Drug-induced rhabdomyolysis Drug-induced tumor lysis Transcellular shi t

ARBs

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Angiotensin I to II conversion inhibition Angiotensin II receptor blockade Aldosterone synthesis inhibition Aldosterone receptor blockade Renal epithelial Na channel; (ENaC) blockade Inhibition o Na-K-ATPase

Medications KCL, penicillin G Beta-blockers, NSAIDs, COX-2 inhibitors ACE inhibitors

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Mechanism Increased potassium load Renin release inhibition

Potassium excretion in the distal nephron depends upon adequate urine ow, aldosterone, and activity o the basolateral Na+/K+-ATPase. The reabsorption o luminal Na+ through aldosterone-sensitive epithelial sodium channels (ENaCs) creates an electrochemical gradient or K+ excretion in the urine. Hyperkalemia can occur in aldosterone-resistant or de cient states by attenuating the electrochemical gradient or K+ secretion. Acquired mineralocorticoid resistance rom diabetes mellitus, obstructive uropathy, chronic tubulointerstitial disease, sickle cell anemia, lupus nephritis, and medications, as well as decreased mineralocorticoid production (including medication induced), are commonly associated with type IVrenal tubular acidosis (RTA). Type IVRTA is characterized by hyperkalemia, normal anion gap hyperchloremic acidosis, with serum HCO3 values ranging between 16 and 22 mmol/L, and decreased urinary NH4+ production, causing a positive urine anion gap [Urine (Na+) + (K+) – (Cl–)]. In acute and chronic tubular injury, a decreased responsiveness to aldosterone can contribute to hyperkalemia. For acute kidney injury associated with prerenal azotemia or hypovolemic states, decreased urinary ow to the distal tubule and a reduction in sodium-potassium exchange can contribute to hyperkalemia.

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TABLE 241-1 Medications Associated with Hyperkalemia

Decreased potassium excretion

PRACTICE POINT Redistribution of potassium Redistribution o potassium rom the intracellular to the extracellular space can occur in severe acidosis due to nonorganic acid metabolic acidosis, hyperosmolar states, tissue breakdown, and hyperkalemic periodic paralysis. Organic acids such as lactic acid and ketoacids are less likely to cause hyperkalemia than nonorganic acids. These organic acids have greater transmembrane mobility, allowing movement into cells with H+, rather than movement o K+ out o cells in exchange or H+. Hyperkalemia in diabetic ketoacidosis usually results rom insulin de ciency and hyperosmolality, rather than acidosis. Hyperglycemia increases extracellular osmolality, drawing water rom cells down the osmotic gradient. Potassium ollows the water movement (solvent drag), and hyperkalemia results. Tissue breakdown may liberate large amounts o intracellular potassium, resulting in rapid, li e-threatening increases in extracellular potassium. Rhabdomyolysis, tissue necrosis, tumor lysis with chemotherapy, and large hematomas are common causes. In rhabdomyolysis, hypokalemia may precede hyperkalemia, and contribute to muscle breakdown by causing vasoconstriction and decreased blood ow to the involved muscle. Hyperkalemic periodic paralysis is an autosomal dominant disorder involving the muscle cell sodium channel. During these episodes, potassium moves rom the intracellular to extracellular space, accompanied by movement o sodium and water into the cell. The hyperkalemia is accompanied by transient weakness or paralysis.

• •

In the setting o acute kidney injury, hyperkalemia associated with rapid transcellular potassium shi ts rom the intracellular to extracellular compartment can be seen with rhabdomyolysis, tissue necrosis, tumor lysis, and large hematomas. Hyperkalemia in this setting may progress rapidly to cause li ethreatening arrhythmias. Emergent nephrology consultation or possible dialysis is required.

■ SIGNS AND SYMPTOMS Clinical e ects o hyperkalemia relate to altered membrane excitability due to changes in the transcellular potassium gradient. Severe hyperkalemia leads to cardiac arrhythmias and conduction abnormalities. It may also cause weakness o the lower extremities, progressing superiorly to cause accid paralysis and respiratory ailure. This presentation may mimic Guillain-Barré syndrome, but is easily di erentiated by the response to potassium correction. Hyperkalemia may also contribute to metabolic acidosis by inter ering with renal ammonium excretion.

■ EVALUATION OF HYPERKALEMIA IN THE HOSPITALIZED PATIENT In the hospital setting, the initial evaluation o hyperkalemia includes monitoring or li e-threatening arrhythmias, checking or pseudohyperkalemia, eliminating exogenous sources o 1973

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Re che ck pla s ma a fte r ra pid s e pa ra tion of nonhe molyze d s a mple. K+ norma lize d?

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Ongoing IV or ora l s ource s of exce s s pota s s ium? me dica tions a s s ocia te d with hype rka le mia ? (commonly ACE, ARB, NSAIDs, K+ s pa ring diure tics )

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Prima ry hypoa ldos te ronis m S e conda ry hypoa ldos te ronis m

Figure 241 1 Diagnostic assessment of hyperkalemia. (ACE, angiotensin-converting enzyme inhibitor; ARB, angiotensin receptor blocker; DKA, diabetic ketoacidosis; ECG, electrocardiogram; GFR, glomerular filtration rate; HHS, hyperosmolar hyperglycemic state; NSAIDs, nonsteroidal antiinflammatory drugs.)

potassium, evaluating renal unction, and evaluating or rapid transcellular shi ts o potassium (Figure 241-1). ECG changes Even mildly elevated K+ levels may be associated with ECG changes, especially in the setting o rapid rises in plasma K+ values. I ECG changes rom hyperkalemia are ound or i the plasma K+ value is ≥ 7.0, continuous telemetry is indicated and should continue until the plasma K+ value is ≤ 5.8 and there are no hyperkalemic ECG changes. Frequent chemistry checks are indicated or plasma K+ greater than 5.8 or or hyperkalemia associated with ECG changes, severe hyperglycemia, or any clinical condition which predisposes the patient to rapid changes in plasma K+. Plasma potassium levels do not correlate with speci c ECG changes. A symmetric increase in T wave height may be seen initially. Hyperkalemia-induced peaked T waves may be dif cult to distinguish rom the hyperacute T waves o myocardial injury. As potassium levels rise urther, attening o the P waves, prolongation o the PR interval, and prolonged QRS duration occur. Eventually, atrial standstill and a sine wave ECG pattern may be seen (Figure 241-2). 1974

Urine potassium, transtubular potassium gradient, and urine potassium/creatinine A 24-hour urine K+ measurement can help di erentiate between renal and nonrenal causes o hyperkalemia. With hyperkalemia, urinary excretion o K+ should exceed 40 mmol/d. Alternatively, the transtubular potassium gradient (TTKG), a measurement o potassium secretion by the distal nephron corrected or urine osmolality, has been used: TTKG = (KU/KS) × (SOsm/UOsm) KU and KS are the concentrations o K+ in the urine and serum, and SOsm and UOsm are the osmolalities o the serum and urine, respectively. Plasma potassium and osmolality can be used instead o serum values to estimate TTKG with minimal e ect on clinical interpretation. The accuracy o the TTKG has been called into question by recent studies o urea and potassium handling in the renal tubule. Previous studies using TTKG have suggested that patients with normal renal unction and normal potassium intake have a TTKG o 8 to 9. In hyperkalemia, a low TTKG (< 5-7) suggests

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De pre s s ion of ST s e gme nts

Figure 241 2 ECG changes associated with hyperkalemia and hypokalemia. (Reproduced, with permission, rom Flomenbaum N, Gold rank LR, Ho man R, et al. eds. Goldfrank’s Toxicologic Emergencies, 8th ed. New York, NY: McGraw-Hill; 2006. Fig. 5-11.)

an inappropriately low secretion o potassium. A high TTKG with hyperkalemia suggests normal aldosterone action and an extrarenal cause o hyperkalemia, except in cases o volume depletion where aldosterone secretion is enhanced with a TTKG > 7, but total renal potassium excretion is limited by low urine ow. When the TTKG is inappropriately low in the setting o hyperkalemia, an increase in the TTKG to >10 hours a ter the administration o 0.05 mg o udrocortisone suggests hypoaldosteronism. I udrocortisone has no e ect on the TTKG, drug-induced or intrinsic renal resistance to aldosterone are likely. I urther studies cast doubt on the use ulness o TTKG, the urine potassium/creatinine ratio will likely be used more requently when a 24-hour urine potassium is not available. It has been suggested that a patient with hyperkalemia and a normal renal response should have a spot urine ratio o >200 mmol K+/g creatinine (=22.6 mmol K+/mmol creatinine). For a typical patient with a daily creatinine excretion o over 1 g/d, this is signi cantly more than the 24-hour urinary K+ excretion o >40 mmol used by some clinicians as a cuto or adequate renal potassium clearance in the setting o hyperkalemia. This urther underscores the point that it is dif cult to de ne an exact cuto or expected renal potassium excretion or urine K+/Cr in the ace o hyperkalemia without additional investigation.

■ TREATMENT OF HYPERKALEMIA Treatments exist or hyperkalemia which cause net excretion or removal o potassium, such as gastrointestinal resins and laxatives

C H A P T E R 2 4 1 P o t a s s i u m a n d M a g n e s i u m D i s o

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Intravenous calcium stabilizes the cardiac membrane by inhibiting membrane depolarization. It is the most important initial treatment or severe hyperkalemia. Two orms o calcium are commonly available: calcium gluconate and calcium chloride. Calcium gluconate is pre erred because it can be administered through a peripheral intravenous line, whereas calcium chloride requires a central venous line to prevent tissue necrosis. Tissue necrosis can occur i calcium chloride leaks rom the venous access into the surrounding tissue. A 10 mL ampule o calcium gluconate contains 90 mg (2.3 mmol) o elemental calcium, and a 10 mLampule o calcium chloride contains 272 mg (7.0 mmol) o elemental calcium. The initial dose o calcium gluconate is 10 mL o 10% solution in used over 2 to 3 minutes. An equivalent amount o elemental calcium is contained in 3.3 mL o 10% calcium chloride. The onset o action is 1 to 3 minutes, and duration o action is 30 to 60 minutes. Calcium cannot be mixed with bicarbonate solutions, because precipitation o CaCO3 occurs. Administration o intravenous calcium to patients taking digoxin requires extreme caution, as calcium has been shown to potentiate the e ects o digoxin toxicity in animal models, especially at very rapid in usion rates. The risk o calcium administration in this setting can be reduced by in using the calcium gluconate over 20 to 30 minutes. Another option is to administer digoxin immune ab to neutralize the e ect o the digoxin.

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or hemodialysis. As these therapies may not act immediately or may involve logistical dif culties, they are o ten used in conjunction with short-acting temporizing measures, such as cardiac membrane stabilization with calcium, and agents such as insulin that cause transcellular potassium shi ts (Table 241-2).

PRACTICE POINT

•

In the setting o digoxin toxicity, mild hyperkalemia (serum K+ > 5.0 mmol/L) has been linked to signi cant mortality, and digoxin immune ab may be indicated.

Potassium redistribution Insulin is the most reliable means o inducing transcellular potassium shi ts. The usual dose is 10 units o regular insulin intravenously, ollowed immediately by 50 mL o 50% dextrose (25 g o dextrose). For a blood glucose > 250, insulin can be administered alone with close glucose monitoring. The e ect begins in 10 to 20 minutes, peaks at 30 to 60 minutes, and lasts 4 to 6 hours. Potassium levels typically drop by 0.5 to 1.2 mmol/L. An in usion o 10 units o regular insulin can also be administered over 1 hour in 10% dextrose. Beta-2 agonists have an additive e ect with insulin in transiently reducing plasma potassium by redistribution. High doses o nebulized albuterol are used, typically 10 to 20 mg o nebulized albuterol in 4 mL o normal saline over 10 minutes. Plasma potassium levels usually all by 0.5 to 1 mmol/L. The e ect begins in 30 minutes, peaks at 90 minutes, and lasts 2 to 4 hours. Intravenous albuterol has also been used, but it is not available in the United States. As some patients, including those with renal ailure, have a reduced response to albuterol, it should not be the only agent used. Caution should be exercised or individuals at risk or side e ects such as cardiac ischemia rom the resulting increase in heart rate. Sodium bicarbonate (NaHCO3) does not reliably lead to the redistribution o potassium, and it should not be considered as rst-line therapy or hyperkalemia. This is especially true in high anion gap acidosis, where hyperkalemia is usually not a direct consequence o the presence o organic acids. I intravenous or oral NaHCO3 is 1975

Mechanism Cardiac membrane stabilization

Treatment Calcium

Dose Calcium gluconate 10 mL o 10% solution in used over 2-3 min.

Onset 1-3 min

Duration 30-60 min

Redistribution

Insulin

10-20 min

4-6 h peak 30-60 min

Redistribution

Beta-2 agonist

10 units regular insulin IV. I BG < 250 mg/dL, give 50 mL o 50% dextrose. Albuterol 10-20 mg nebulized.

30 min

2-4 h peak 90 min

Removal

Kayexalate

Removal

Hemodialysis

30-60 g oral in 20% sorbitol 1-2 h or 60 grams in 250 mL water by retention enema. — Immediate

Comments Do not mix with bicarbonate; extreme caution i on digoxin; calcium chloride is an alternative, but poses a risk o tissue necrosis, and requires a central line Most reliable treatment to induce redistribution

Dose is signi icantly higher than dose or respiratory treatments; use with caution in patients at risk or side e ects such as tachycardia and myocardial ischemia Variable Risk o colonic necrosis i used in postoperative patients; do not use sorbitol ormulation when administering via enema Same as dialysis Intermittent or continuous duration

used to treat metabolic acidosis caused by nonorganic anions, which is usually associated with a normal anion gap, plasma potassium may all, but it is not pre erred treatment even in this setting. Oral NaHCO3 is use ul or chronic treatment o type IV renal tubular acidosis.

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TABLE 241-2 Treatment of Hyperkalemia

Potassium removal Sodium polystyrene sul onate (Kayexalate) exchanges Na+ or K+ in the gastrointestinal tract. When taken orally, sorbitol has been typically added to the resin to speed passage through the gastrointestinal tract. However, an FDA warning has been issued about the risk o colonic necrosis when kayexalate is used with sorbitol, and thus the powdered orm o kayexalate not premixed with sorbitol is preerred. I Kayexalate with sorbitol is the only orm available, diluting with water is appropriate. Each gram o resin binds 0.5 to 1.2 mmol o K+. Oral doses o 15 to 60 g are typical. Sodium polystyrene sulonate can also be administered rectally as a retention enema, at a dose o 30 to 60 g in 250 mL o water every 6 hours. The solution should be introduced by gravity, ushed with an additional 50 to 100 mL o nonsodium containing uid, retained 30 to 60 minutes or longer, and cleansed with 250 to 1000 mL o nonsodium containing solution at body temperature. Sorbitol should not be used rectally due to risk o colonic necrosis. Oral or rectal Kayexalate should not be used in postoperative patients or the same reason. Favorable data have been published or two novel potassium reduction agents. Sodium zirconium cyclosilicate (ZS-9) is a highly selective potassium trap, whereas patiromer is a nonabsorbed polymer which exchanges calcium or potassium, primarily in the distal colon. Patiromer is FDA approved, ZS-9 is under FDA review, and urther studies are needed to evaluate their suitability or acute potassium reduction. Initial studies have ocused on their use or more chronic potassium reduction, which may allow broader use o potassium-sparing medications. Dialysis is required or treatment o re ractory hyperkalemia. Intermittent hemodialysis removes potassium most rapidly. Continuous renal replacement therapy is an option or patients who have ongoing causes o severe hyperkalemia, such as tissue necrosis or rhabdomyolysis. Peritoneal dialysis provides gradual removal o potassium. Although peritoneal dialysis is rarely used in developed countries when the other modalities are available, peritoneal dialysis is an established therapy or acute kidney injury. Since electricity is not required or its use and access is placed in the peritoneal cavity

1976

rather than in large veins, it is an option or hyperkalemia treatment in a variety o situations such as dif culty with placing vascular access or hemodialysis, disasters associated with overwhelming caseloads, or power ailure Diuretics are unreliable or the acute treatment o hyperkalemia in the setting o compromised renal unction. In patients with adequate renal unction, the combination o a loop and thiazide diuretic is more e ective or potassium removal than either alone. O the loop diuretics, torsemide and bumetanide have higher bioavailability than urosemide. Potassium intake reduction The typical daily potassium intake or a patient with end-stage renal disease is 2000 mg (51 mmol) o potassium per day, but patients with acute kidney injury may require even more stringent potassium restriction. HYPOKALEMIA

■ ETIOLOGY Hypokalemia (K+ < 3.5 mmol/L) can result rom redistribution, increased potassium excretion rom renal and nonrenal sources, or decreased potassium intake. Medications, especially loop and thiazide diuretics, requently cause hypokalemia. Hypokalemia is common with tubular toxins such as amphotericin B and cisplatin. High doses o penicillin or semisynthetic penicillins such as ticarcillin and carbenicillin occasionally cause renal potassium wasting in the distal nephron due to a transient anion e ect. Inhalation o toluene (glue snif ng) may cause distal renal tubular acidosis with associated hypokalemia. Pseudohypokalemia Falsely low serum or plasma potassium values may occur in conditions such as acute leukemia due to time-dependent uptake o potassium by the increased abnormal white cell mass. Rapid analysis o the sample, or storing the sample at 4°C prior to analysis, can prevent the potassium uptake and con rm the diagnosis o pseudohypokalemia. Redistribution Insulin directly stimulates potassium entry into cells by increasing the activity o the Na+/K+-ATPase pump. This mechanism is independent

Aldosterone-producing adenomas (Conn syndrome) cause hypertension and hypokalemia by stimulation o aldosterone receptors in the distal renal tubule. Cortisol also activates the aldosterone receptor. Normally, cortisol is converted to cortisone by 11-beta-hydroxysteroid dehydrogenase-2 (11βHSD-2) be ore it can reach the aldosterone receptor. Very high cortisol levels, as seen in Cushing syndrome, overwhelm the ability o 11βHSD-2 to degrade cortisol to cortisone, and the nondegraded cortisol activates the aldosterone receptor in the distal tubule and precipitates hypokalemia. Similarly, glycyrrhizinic acid, a component o black licorice that is sometimes added to chewing tobacco, inhibits 11βHSD-2, preventing cortisol degradation and causing hypertension and hypokalemia. With vomiting and nasogastric suctioning, potassium wasting in the urine occurs through aldosterone secretion in the setting o volume depletion, as noted above. Hypokalemia can be associated with an RTA, due to disease o either the proximal (type II RTA) or distal (type I RTA) renal tubules. Either can result rom autoimmune, genetic, endocrine, medication-induced, toxin-induced, or idiopathic causes. Rare causes o hypokalemia associated with metabolic alkalosis involve de ects in the thick ascending limb o Henle transport proteins (Bartter syndrome), mutations in the thiazide-sensitive Na+/Cl– cotransporter in the distal convoluted tubule (Gitelman syndrome), or increased activation o the epithelial sodium channel (ENaC) in the distal tubule (Liddle syndrome). Decreased potassium intake Decreased potassium intake is rarely a cause o hypokalemia, except in severe malnutrition. For patients with normal renal unction who consume the recommended 4700 mg (120 mmol) o potassium per day, 90% (108 mmol) is excreted in the urine. When intake is sharply reduced, urinary potassium loss decreases to < 15 to 20 mmol/d in order to conserve potassium.

■ SIGNS AND SYMPTOMS Individuals with serum potassium levels between 3.0 and 3.5 mEq/L are o ten asymptomatic. However, there is a risk o cardiac arrhythmias or individuals with predisposing conditions such as coronary artery disease. At serum potassium levels between 2.5 and 3.0 mEq/L,

C H A P T E R 2 4 1 P o t a s s i u m a n d M a g n e s i u m D i s o r d

Renal potassium loss

An algorithm or the diagnosis o hypokalemia is presented in Figure 241-3. Pseudohypokalemia and transcellular shi ts should be excluded. Magnesium levels should be measured early in the workup o hypokalemia. Many disorders, such as diarrhea and excess diuresis, deplete both potassium and magnesium. Moreover, hypomagnesemia may lead to renal potassium wasting via potassium channels in the distal tubule, and make hypokalemia more re ractory to treatment. The next step is determining whether hypokalemia arose rom a renal or nonrenal source. An obvious cause may be apparent, such as pro use diarrhea or escalating doses o a loop or thiazide diuretic. When the cause o hypokalemia is unclear, a 24-hour urine potassium measurement may di erentiate between renal and nonrenal losses. In the setting o hypokalemia, urinary K+ losses should all to less than 15 to 20 mmol/d. Potassium excretion above this level suggests a renal contribution to hypokalemia. When a 24-hour urine K+ is not available, a spot urine ratio o 22 mmol K+/g creatinine (=2.5 mmol K+/mmol creatinine) marks the cuto between hypokalemia secondary to intracellular shi ts (i < 22 mmol K+/g Cr) and renal loss (i >22 mmol K+/g creatinine). The TTKG (see above) has been used to help establish the cause o hypokalemia, but the use o TTKG has been cast into doubt by recent studies o urea and K+ handling in the renal tubule. An inappropriately high TTKG (> 4) in hypokalemia has been interpreted as suggesting an increased distal potassium secretion and renal potassium loss. A low TTKG can occur with nonrenal potassium wasting, with urinary potassium losses rom osmotic diuresis, with hypokalemia secondary to diuretics which were discontinued at the time o TTKG measurement, or with hypokalemia associated with K+ shi ts. Patients with renal potassium wasting should be urther classi ed by acid-base status. Patients with acidosis may have RTA, diabetic ketoacidosis, or tubular dys unction rom drugs such as amphotericin B or acetazolamide. Patients with alkalosis and hypertension may have mineralocorticoid excess or Liddle syndrome. Hypokalemia with alkalosis and normal or low blood pressure may be caused by vomiting, diuretics, and Bartter or Gitelman syndrome. The spot urine chloride is a use ul diagnostic tool in evaluating the etiology o hypokalemia in the setting o metabolic alkalosis, with a spot low urine chloride (< 10 mmol/L) suggesting volume depletion and a chloride-responsive state.

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Common nonrenal causes o hypokalemia include intestinal loss o potassium rom diarrhea, celiac disease, ileostomy, and chronic laxative abuse. Potassium loss rom vomiting and nasogastric suctioning can result in hypokalemia, although renal potassium losses rom aldosterone activation may be more important in this setting. Potassium losses through the skin are usually low, except in the setting o extreme physical exertion. Severe burns may lead to hypokalemia by multiple mechanisms.

■ EVALUATION OF HYPOKALEMIA

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Nonrenal potassium losses

patients report generalized weakness and constipation. When serum potassium levels drop below 2.5 mEq/L, there is an increased risk o muscle necrosis and rhabdomyolysis. At serum potassium levels less than 2.0 mEq/L, ascending paralysis and respiratory ailure can occur.

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o stimulation o cellular glucose entry. Beta-2-adrenergic activators stimulate Na+/K+-ATPase mediated cellular potassium uptake by a slightly di erent cellular mechanism. Thus, insulin and beta-2-adrenergic activation may act synergistically to cause hypokalemia. Aldosterone stimulates direct cellular uptake and redistribution due to increased Na+/K+-ATPase activity. It also acts in the distal renal tubule to enhance potassium excretion. Thyrotoxic periodic paralysis causes severe hypokalemia by redistribution, in conjunction with extremity and limb girdle weakness, hypophosphatemia, and hypomagnesemia. It is more common in patients o Asian and Hispanic origin. Attacks o ten occur during rest a ter vigorous physical activity, and can also be precipitated by carbohydrate-rich meals. Other rare genetic orms o hypokalemic periodic paralysis also exist.

ECG changes ECG changes in hypokalemia are shown in Figure 241-2. U waves appear ollowing the T waves, and become progressively more prominent in comparison to the T waves as potassium levels decrease. Ultimately, the U wave merges with the T wave, and the QT interval appears prolonged.

■ TREATMENT OF HYPOKALEMIA Potassium repletion is the cornerstone o therapy or hypokalemia. As extracellular potassium comprises a raction o the total body potassium store, relatively large amounts o potassium are required to correct the total body potassium de cit. A plasma K+ 1 mmol/L below normal corresponds to a total body potassium de cit o approximately 200 to 400 mmol, and a drop in plasma K+ to 2 mmol/Lbelow normal requires 400 to 800 mmol or repletion. Typically, daily repletion is signi cantly less than the total body de cit as the time required or redistribution is prolonged. Underlying disorders such as metabolic alkalosis that 1977

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K < 3.5 mmo l/L (Eva lua te ne e d for e me rge nt re ple tion prior to a dditiona l workup)

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S eve re le ukocytos is with a bnorma l le ukocyte s ?

Re che ck pla s ma a fte r ra pid s e pa ra tion or s toring a t 4°C Hypoka le mia re s olve d?

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No

Ye s

Ps e udo hypo kale mia

No

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S ource s of tra ns ce llula r s hift?

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Nonre na l los s ? (profus e dia rrhe a , s eve re burns )

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Diure tic induce d los s ? Polyuria or (e s pe cia lly thia zide or loop diure tic)

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No Low

K ≥ 3.5 a fte r Mg re ple tion?

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Hypoma gne s e mia

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Plas ma mag ne s ium

No

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Norma l or high

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Urine K+

> 20 mmol/d (Re na l los s )

< 20 mmol/d

Nonre na l los s Previous vomiting Previous diure tic us e Poor die ta ry inta ke

Ac id bas e s tatus

Acidos is

Alka los is

Dis ta l (Type I) RTA Proxima l (Type II) RTA DKA Amphote ricin B Ace ta zola mide

Blo o d pre s s ure

High

Mine ra locorticoid exce s s Liddle syndrome

Low or norma l

Loop, thia zide diure tics Vomiting, ga s tric s uction Ba rtte r syndrome Gite lma n syndrome

Figure 241 3 Diagnostic assessment of hypokalemia. (DKA, diabetic ketoacidosis; RTA, renal tubular acidosis.)

are causing or perpetuating hypokalemia must also be addressed. Continuous telemetry and requent electrolyte checks should be perormed in severe hypokalemia, or in conditions in which the serum potassium may decline rapidly, such as diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state (HHS). Oral repletion I there is no immediate threat to li e, oral potassium can be used to treat hypokalemia. Generally, potassium chloride (KCl) is indicated or hypokalemia associated with diuretic use or volume depletion. A typical initial dose in a patient with normal renal unction is 40 1978

to 100 mmol (40-100 mEq) per day, in two to three divided doses. Liquid, wax matrix, and microencapsulated orms exist. Compliance is poor with the liquid orm due to the strong taste. Although the wax matrix orm is easier to swallow, it has been associated with erosions o the gastrointestinal tract. The microencapsulated ormulation is associated with the ewest complications. Other potassium preparations are available or di erent indications. Oral potassium phosphate is ound in many oods, and is indicated or combined potassium and phosphorus depletion. Terminology may be misleading. For example, Neutra-Phos actually has more potassium than K-Phos. Potassium bicarbonate is use ul

PRACTICE POINT

•

Extreme caution and requent monitoring are required in the treatment o hyperkalemia in diabetic ketoacidosis and hyperosmolar hyperglycemic state. Generally, these patients have a total body potassium de cit. Administration o insulin drives potassium intracellularly through direct stimulation o Na+/K+-ATPase, while both insulin and intravenous uids reduce the glucose-induced hyperosmolality that drives solvent drag. These two interventions can lead to a rapid decrease in plasma potassium.

PRACTICE POINT

•

Potassium should not be mixed with glucose-containing solutions, because the glucose will stimulate insulin secretion and drive potassium rom the extracellular to the intracellular space.

C H A P T E R 2 4 1 P o t a s s i u m a n d M a g n e s i D i s o

Magnesium unit conversion • 41.2 mmol o elemental magnesium is equivalent to 1 g o magnesium (24.3 mg = 1 mmol). Since the charge o the magnesium cation is 2+, 1 mmol = 2 mEq. For a common preparation used or IVmagnesium repletion, 1 g o magnesium sul ate (MgSO47H2O) contains 8.1 mEq (98.6 mg) o elemental magnesium.

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PRACTICE POINT

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The use o insulin in DKA and HHS drives potassium into the intracellular space, and also decreases the hyperglycemia-induced osmolar driving orce or movement o potassium rom the intracellular to the extracellular space. Rapid and sometimes li e-threatening potassium shi ts may result. In 2009, the American Diabetes Association recommended that insulin should not be started until the serum potassium is known. I the serum potassium is < 3.3 mmol/L, insulin therapy is held until the potassium is repleted to 3.3 mmol/L or above. I the serum potassium is ≥ 3.3 mmol/L, insulin therapy can be initiated. For serum potassium ≥ 3.3 and < 5.2 mmol/L, potassium supplementation as 20 to 30 mEq K+ in each liter o IV uid is given during insulin therapy. The goal is to achieve serum potassium values between 4 to 5 mmol/L. Potassium supplementation is initially held or serum potassium values > 5.2 mmol/L, but is o ten subsequently required, as total body stores o potassium are usually depleted and insulin plus intravenous uid therapy eventually unmasks the total body potassium de cit.

A typical American diet contains 300 to 400 mg/d o elemental magnesium. Approximately 30% to 40% o dietary magnesium is absorbed in the gut. Additionally, 40 mg/d o magnesium is secreted in the small intestine, o which 20 mg/d is reabsorbed in the colon and rectum. Approximately 100 mg appears in the urine each day, which is 5% o the ltered load. Speci c cuto s or hypomagnesemia and hypermagnesemia are dif cult to establish because o the poor correlation between extracellular concentration and total body stores. Plasma magnesium levels o 1.7 to 2.3 mg/dL (0.70-0.95 mmol/L) are considered normal, but a normal serum level may be present despite total body magnesium depletion.

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Hypokalemia in DKA and HHS

MAGNESIUM BALANCE

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KCl is pre erred or intravenous repletion. Potassium phosphate may be used or dual phosphorus and potassium depletion. Potassium can be in used through a peripheral intravenous line at a maximum rate o 10 mmol/h. Higher rates require a central venous line and continuous ECG monitoring. In usion rates o 20 to 40 mmol/h are reserved or cases o li e-threatening hypokalemia requiring emergent correction. One liter bags o IV uids typically have a maximum o 60 mEq o K+ added in order to avoid in using an excess amount o K+. Intravenous potassium is a common cause o iatrogenic hyperkalemia. A typical intravenous dose with normal renal unction is 20 to 40 mmol (20-40 mEq). Although 20 mmol o intravenous KCl might increase plasma K+ by 0.25 mmol/L, transcellular shi ts make it dif cult to predict the e ect o therapy. Renal potassium clearance generally decreases signi cantly at a GFR below 20 to 30 mL/min/1.73 m 2, and requires reduction in potassium dosing and additional monitoring.

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Intravenous repletion

Aggressive potassium repletion or this disorder has been associated with a 25% or greater incidence o hyperkalemia, so i oral or IV potassium is given, subsequent close serial monitoring o plasma potassium is warranted. Treatment to establish a euthyroid state is the long term priority to prevent uture attacks.

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or the treatment o both metabolic acidosis and hypokalemia, while potassium citrate may prevent renal stones.

HYPOMAGNESEMIA

■ ETIOLOGY OF HYPOMAGNESEMIA Hypomagnesemia results rom low dietary intake, gastrointestinal losses, and renal losses. Poor intake o magnesium is common in alcoholics and hospitalized patients receiving inadequate magnesium supplementation in parenteral nutrition or intravenous uids. The causes o impaired gastrointestinal absorption include diarrhea, in ammatory bowel disease, laxative abuse, proton pump inhibitors, and small bowel resection. Osmotic and loop diuretics provoke urinary losses o magnesium. Acutely, thiazide diuretics increase magnesium absorption in the distal convoluted tubule, but long-term use can reduce magnesium reabsorption and cause hypomagnesemia. Urinary magnesium wasting is also seen in alcoholics. Many nephrotoxic drugs, such as amphotericin B, aminoglycosides, cisplatin, oscarnet, and cyclosporine, inter ere with magnesium reabsorption in the thick ascending limb or distal convoluted tubule and cause magnesium wasting. Rare amilial disorders, such as Gitelman syndrome, are also associated with urinary magnesium losses. Miscellaneous causes o hypomagnesemia include acute pancreatitis, in which magnesium and calcium are saponi ed in necrotic at, hungry bone syndrome, where magnesium, calcium, and phosphate are absorbed by bone a ter parathyroidectomy or hyperparathyroidism, and diabetic ketoacidosis, where magnesium levels all due to osmotic diuresis and insulin-related transmembrane shi ts.

■ HYPOMAGNESEMIA AND ASSOCIATED ELECTROLYTE Thyrotoxic hypokalemic periodic paralysis Oral propranolol (3 mg/kg) is rst-line treatment or thyrotoxic periodic paralysis because it rapidly reverses hypokalemia, hypophosphatemia, and hypomagnesemia, and is not associated with rebound hyperkalemia. Propranolol 1 mg IV pushed slowly every 10 minutes, up to a total o 3 mg IV, is an alternative regimen.

ABNORMALITIES Hypokalemia Hypomagnesemia and hypokalemia o ten coexist due to similar common underlying etiologies, such as excess gastrointestinal losses and diuretics. Hypokalemia is o ten dif cult to treat without magnesium repletion. 1979

P A R T V I C l

Intravenous repletion

Elevated ionized serum calcium levels induce renal Mg 2+ wasting. Hypomagnesemia is common in hypercalcemia o malignancy. However, in hypercalcemia secondary to hyperparathyroidism, magnesium de ciency is rare due to the parathyroid hormone (PTH)-induced stimulation o renal Mg 2+ reabsorption.

Symptomatic or severe hypomagnesemia should be treated with intravenous magnesium. For active seizures or cardiac arrhythmias, an initial dose o 8 to 16 mEq o Mg 2+ (1-2 g o MgSO47H2O) is administered over 2 minutes. For nonemergency repletion, 64 mEq o Mg 2+ (8 g o MgSO47H2O) can be given over the rst 24 hours, ollowed by 32 mEq o Mg 2+ daily or six additional days. Since magnesium is renally cleared, the dose should be reduced by 25% to 50% and the plasma magnesium level monitored a ter each dose or GFR < 20 to 30 mL/min/1.73 m 2.

Hypocalcemia Hypomagnesemia may cause hypocalcemia due to inhibition o PTH secretion and by induction o skeletal resistance to PTH. Hypocalcemia may be present in up to hal o patients with hypomagnesemia.

■ ETIOLOGY

Mild hypomagnesemia may be asymptomatic. Severe hypomagnesemia leads to neuromuscular, neurologic, and cardiovascular symptoms. Neuromuscular abnormalities include hyperre exia, carpopedal spasm, delirium, seizures, tetany, and paralysis. Chvostek and Trousseau signs may be present. ECG mani estations include torsades de pointes, premature ventricular contractions, ventricular tachycardias, and ventricular brillation. There is also an increased risk o digitalis cardiac toxicity. As serum magnesium levels do not always correlate with total body magnesium stores, normomagnesemic magnesium depletion may be considered in patients with unexplained hypocalcemia and hypokalemia and clinical risk actors or magnesium de ciency.

Hypermagnesemia usually results rom iatrogenic causes, such as magnesium treatment or preeclampsia or eclampsia, or inadvertent administration o excessive doses o magnesium-containing supplements, laxatives, Epsom salts, enemas, or antacids. The risk o hypermagnesemia is particularly high or patients with severely impaired renal unction.

e t t i n g

■ EVALUATION OF HYPOMAGNESEMIA Urine studies Urine studies are use ul to evaluate renal vs nonrenal causes o hypomagnesemia. The ractional excretion o magnesium (Fe Mg ) is given by: Fe Mg =

(Urine Mg)(Plasma Creatinine) 0.7(Plasma Mg)(Urine Creatinine)

The 0.7 in the denominator is a correction actor or the 30% o plasma magnesium bound to plasma proteins. A Fe Mg o > 3% in a patient with normal GFR indicates renal magnesium loss. A 24-hour magnesium collection can also be obtained and is normally 3 to 5 mmol (75-125 mg)/24 hours. In the presence o hypomagnesemia, normal kidneys should be able to reduce the 24-hour urinary excretion o magnesium even urther, to 1 mmol or less.

■ TREATMENT OF HYPOMAGNESEMIA Oral repletion

PRACTICE POINT

•

■ CLINICAL MANIFESTATIONS Clinical mani estations are unusual with plasma magnesium levels < 4.5 to 5 mg/dL. Above this range, nausea, vomiting, cutaneous lushing, hypore lexia, and mild hypotension can be seen. For plasma magnesium levels > 7 to 10 mg/dL, there may be loss o tendon re lexes, muscle weakness, and hypotension. Respiratory muscle paralysis occurs when magnesium levels exceed 12 to 15 mg/dL. ECG changes with plasma magnesium values > 5 mg/dL include prolonged PR interval, an increased QRS interval, prolonged QT interval, and bradycardia. Complete heart block is seen or plasma Mg 2+ > 10 to 15 mg/dL, and cardiac arrest or levels > 15 mg/dL.

■ TREATMENT In mild cases, stopping magnesium administration may be su icient. Dialysis can be per ormed or extreme cases. Intravenous calcium (100-200 mg o elemental calcium given over 5-10 minutes) can be used to temporarily antagonize the e ects o magnesium until dialysis can be per ormed. Details regarding intravenous calcium administration can be ound in the section on treatment o hyperkalemia. Intravenous volume in usion may be help ul in promoting magnesium excretion in patients who are not volume overloaded and who have adequate renal unction. DISCHARGE CHECKLIST

The most popular ormulation or oral replacement is magnesium oxide (242 mg = 20 mEq Mg 2+ per 400 mg tablet), with a typical dose o 400 mg two to three times per day. Magnesium chloride, magnesium gluconate, magnesium lactate, and magnesium L-aspartate are other options. Diarrhea is a common side e ect. It may be reduced with the use o a sustained release ormulation, such as magnesium chloride (64 mg per 535 mg tablet). The potassiumsparing diuretics triamterene and amiloride, which block ENaC in the distal renal tubule, can assist in treatment o hypomagnesemia re ractory to oral supplementation.

1980

HYPERMAGNESEMIA

■ CLINICAL MANIFESTATIONS

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Re ractory hypokalemia and hypocalcemia occur with severe Mg 2+ de ciency, and Mg 2+ repletion is necessary or correction.

• For patients with potassium disorders at risk or cardiac arrhyth-

mias, is the potassium level within the normal range prior to discharge? • For patients with potassium disorders at low risk o cardiac arrhythmias, is the potassium level between 3 and 5.6? Are clinical symptoms or ECG changes associated with potassium disorders absent? I the patient is discharged with mild hypokalemia or mild hyperkalemia, is there a clinical plan to achieve a normal plasma potassium (3.5-5) which can be re-evaluated at ollow-up? • Have patients with hypokalemia been counselled regarding potential dietary sources o potassium? (These include dark lea y greens, avocadoes, peaches, prunes, raisins, potatoes, squash, beans, and sh, as well as the commonly cited bananas and orange juice.) • Has ollow-up testing been arranged or potassium, magnesium, and creatinine, i appropriate?

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Kitabchi AE, Umpierrez GE, Miles JM, Fisher JN. American Diabetes Association Consensus Statement: hyperglycemic crisis in adult patients with diabetes. Diabetes Care. 2009;32:1335-1343.

Weir MR, Bakris GL, Bushinksky DA, et al. Patiromer in patients with kidney disease and hyperkalemia receiving RAAS inhibitors. N Engl J Med. 2015;372:211-221.

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Kim HJ, Han SW. Therapeutic approach to hyperkalaemia. Nephron. 2002;92(Suppl 1):33-40.

Top JM, Murray PT. Hypomagnesemia and hypermagnesemia. Rev Endocr Metab Disord. 2003;4:195-206.

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Kamel KS, Halperin ML. Intrarenal urea recycling leads to a higher rate o renal excretion o potassium: a hypothesis with clinical implications. Curr Opin Nephrol Hypertens. 2011;20:547-554.

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Park CH, Kim EH, Roh YH, Kim HY, Lee SK. The association between the use o proton pump inhibitors and the risk o hypomagnesemia: a systematic review and meta-analysis. PLoS One. 2014;9:e112558.

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Gennari FJ. Disorders o potassium homeostasis: hypokalemia and hyperkalemia. Crit Care Clin. 2002;18:273-288.

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Packham DK, Rasmussen HS, Lavin PT, et al. Sodium zirconium cyclosilicate in hyperkalemia. N Engl J Med. 2015;373:222-231.

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Bosch X, Poch E, Grau JM. Rhabdomyolysis and acute kidney injury. N Engl J Med. 2009;361:62-72.

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Palmer BF. A physiologic-based approach to the evaluation o a patient with hypokalemia. Am J Kidney Dis. 2010;56:1184-1190.

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SUGGESTED READINGS

1981

242

CHAP TER

Disorders of Sodium and Water Balance Elwaleed A. Elhassan, MD Robert W. Schrier, MD

Key Clinical Questions 1

What is the di erence between sodium and water balance and the regulation o each?

2

How is volume depletion assessed in patients with normal heart unction and in those with underlying cardiac ailure?

3

Which luids are best or volume repletion?

4

How do diuretics work, and what are their side e ects? How can resistance to their action be overcome?

5

How should hyponatremia and hypernatremia be assessed and sa ely corrected?

INTRODUCTION Sodium and water disturbances are among the most commonly encountered disorders in hospitalized and critically ill patients. Sodium and water balance are independently regulated by mechanisms that are designed to maintain circulatory integrity and plasma osmolality, respectively. Sodium balance is regulated by changes in sodium intake and excretion, whereas plasma osmolality is regulated by changes in water intake and water excretion. Water is the predominant constituent o the human body. In healthy individuals, it makes up 60% o male body weight and 50% o emale body weight. Body water is distributed between two compartments: the intracellular uid compartment, containing 55% to 65%, and the extracellular uid compartment, containing the remaining 35% to 45%. The extracellular uid compartment is urther subdivided into the interstitial space and the intravascular space. The interstitial space comprises approximately 75% o the extracellular uid compartment, whereas the intravascular space contains 25%. Total body water di uses reely between the intracellular space and the extracellular space in response to solute concentration gradients. There ore, the amount o water in each compartment depends entirely on the quantity o solute in that compartment. The major extracellular solute is sodium, while potassium is the major intracellular solute. This solute distribution is maintained by active transport, via the Na+/K+-ATP-dependent pumps ound on cell membranes. PATHOPHYSIOLOGY OF SODIUM BALANCE The extracellular uid compartment depends on the total body sodium content as well as the integrity o the mechanisms responsible or its maintenance. Sodium content is normally tightly regulated by modulating renal retention and excretion when there is de ciency or excess o extracellular uid. The operative homeostatic mechanisms include an a erent sensing limb and an e erent e ector limb. Disorders o either sensing or e ector mechanisms can lead to ailure to adjust renal sodium handling, resulting in hypertension and edema with positive sodium balance, or hypotension and hypovolemia with negative sodium balance.

■ EFFECTIVE ARTERIAL BLOOD VOLUME E ective arterial blood volume re ers to the blood volume detected by baroreceptors in the arterial circulation. The e ective arterial blood volume can change independently o the total extracellular uid volume, leading to sodium and water retention in di erent clinical situations. Af erent limb sensing sites include low-pressure cardiopulmonary receptors (atrial, ventricular, and pulmonary stretch receptors), high-pressure arterial baroreceptors (carotid, aortic arch, and renal sensors), and central nervous system and hepatic receptors. Activation o these a erent sites engages several ef ector mechanisms. Activation o the sympathetic nerves stimulates proximal tubular sodium reabsorption. Renin release rom the renal juxtaglomerular apparatus stimulates the ormation o angiotensin II, a potent vasoconstrictor. Angiotensin II also stimulates the adrenal gland to secrete aldosterone, which increases tubular sodium reabsorption. Other e ector mechanisms include prostaglandins that modulate renal blood ow and sodium handling, natriuretic peptides that enhance renal sodium excretion in response to atrial stretching, and 1982

Extrarenal causes The gastrointestinal tract is the most common extrarenal source o uid loss. Vomiting or nasogastric suction may cause volume loss with metabolic alkalosis. Diarrhea may result in volume depletion with metabolic acidosis. Third-space sequestration, excessive sweat production, and loss o skin barrier rom burns or exudative skin lesions may lead to signi cant ECF volume depletion. Hemorrhage, as rom gastrointestinal bleeding or trauma, may lead to signi cant volume loss. Renal losses Diuretics may cause renal sodium wasting, volume contraction, and acid-base disturbances i abused or inappropriately prescribed. Genetic and acquired tubular disorders can result in renal sodium wasting and volume contraction. Mineralocorticoid de ciency or resistance may lead to renal sodium wasting. This may occur in the setting o primary adrenal insuf ciency (Addison disease), hyporeninemic hypoaldosteronism secondary to diabetes mellitus, or other chronic interstitial renal diseases. Severe hyperglycemia or high levels o blood urea a ter relie o urinary tract obstruction can lead to obligatory renal sodium and water loss secondary to glucosuria or urea diuresis, respectively. Clinical manifestations The symptoms o hypovolemia are nonspeci c. They range rom mild postural symptoms, thirst, muscle cramps, and weakness, to drowsiness and disturbed mentation with pro ound volume loss. Physical examination may reveal tachycardia, cold clammy skin, postural or recumbent hypotension, and reduced urine output depending on the degree o volume loss (Table 242-1). Rarely, diminished skin turgor may be seen. Reduced jugular venous pressure (JVP) noted at the base o the neck is a use ul parameter o volume depletion and may roughly estimate the central venous pressure (CVP). However, an elevated CVP does not exclude hypovolemia in patients with underlying cardiac ailure or pulmonary hypertension.

C H A P T E R 2 4 2 D i s o r d e r s o S o d i u m a n d W a t e r B a

Extracellular uid (ECF) volume contraction is caused by loss o sodium and water in excess o intake. This may result rom renal losses, extrarenal losses, or sequestration in potential spaces, such as the peritoneal cavity, retroperitoneum, pleural spaces, or muscles, which are not in hemodynamic equilibrium with the ECF (“third-spacing”).

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■ EXTRACELLULAR FLUID VOLUME CONTRACTION

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DISORDERS OF SODIUM BALANCE

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Osmoregulation is the regulation o water intake and excretion to maintain constant body osmolality (tonicity). Disorders o water homeostasis result in hypo- or hypernatremia, whereas disorders o total body sodium content result in extracellular volume depletion or excess. Since osmolality in all body uids is essentially equal, it can be estimated by measuring the plasma osmolality. The normal plasma osmolality is 275 to 290 mOsm/kg. It is kept within this range by hypothalamic osmoreceptors, which are capable o sensing a 1% to 2% change in tonicity. Osmoreceptors provoke thirst and release o the antidiuretic hormone AVP. The combined e ect o AVP stimulation and thirst results in water intake and retention, lowering plasma osmolality and sodium concentration by dilution, whereas suppression o thirst and AVP secretion leads to the contrary.

Mild to moderate volume loss • Thirst • Delayed capillary re ill • Postural dizziness and weakness • Dry mucous membranes and axillae • Cool clammy extremities and collapsed peripheral veins • Tachypnea • Tachycardia with pulse rate > 100 beats/min or postural pulse increment o 30 beats/min or more • Postural hypotension (systolic blood pressure decrease o > 20 mm Hg with standing) • Low jugular venous pulse • Oliguria Severe volume loss and hypovolemic shock • Depressed mental status or loss o consciousness • Peripheral cyanosis • Reduced skin turgor (in young patients only) • Marked tachycardia, low pulse volume • Supine hypotension (systolic blood pressure < 100 mm Hg)

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■ REGULATION OF WATER BALANCE

TABLE 242-1 Clinical Evaluation of Extracellular Fluid Volume Depletion

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pituitary secretion o arginine vasopressin (AVP), a modest vasoconstrictor that also enhances renal water retention.

The absence o symptoms or obvious physical ndings does not preclude volume depletion in an appropriate clinical setting, and hemodynamic monitoring or administration o a uid challenge may sometimes be necessary. Laboratory ndings consistent with volume depletion include hemoconcentration and increased serum albumin concentration. However, anemia or hypoalbuminemia may con ound interpretation o these laboratory values. In healthy individuals, the ratio o blood urea nitrogen (BUN) (mg/dL) to serum creatinine (mg/dL) approximately equals 10. In volume depletion, this ratio increases because o a di erential increase in the tubular reabsorption o urea. Several clinical conditions con ound this ratio. Upper gastrointestinal hemorrhage and administration o corticosteroids increase urea production and the ratio o BUN to creatinine. Malnutrition and underlying liver disease diminish urea production, and thus the BUN-to-creatinine ratio is less use ul in these clinical settings. In the absence o renal salt wasting or diuretics, elevated urine osmolality and speci c gravity may indicate hypovolemia. Hypovolemia normally triggers avid renal sodium reabsorption, resulting in low urine sodium concentration and low ractional excretion o sodium. The ractional excretion o sodium (FENa) is calculated using the ollowing ormula: FENa = [UNa × PCr/ UCr × PNa] × 100, where UNa and UCr are urinary sodium and creatinine concentrations, and PNa and PCr are plasma sodium and creatinine concentrations, respectively. Decreased FENa (< 1%) is consistent with ECF volume depletion. However, arterial under lling due to low cardiac output or systemic arterial vasodilatation, as in cirrhosis, is also associated with a FENa less than 1%, in spite o increased ECF and edema. Treatment Volume depletion is treated by replacing uid de cits and ongoing losses with a replacement uid closely resembling the lost uid. Clinical parameters help to distinguish mild to moderate rom severe volume loss (Table 242-1), but invasive monitoring may be needed in some patients. Mild volume contraction can usually be corrected via the oral route. In hypovolemic shock with evidence o li e-threatening circulatory collapse or organ dys unction, 1983

P A R T V I C l i n i c a l C o n d i t i o n s i n t h e I n p a t i e n t S e t t i n g

intravenous uid must be given as rapidly as possible until clinical parameters improve. A slower, more judicious approach is warranted in the elderly and in those with underlying cardiac conditions to avoid overcorrection with subsequent pulmonary edema. Crystalloid solutions are e ective, as they distribute primarily in the ECF. Isotonic saline is usually the initial replacement uid o choice in volume-depleted patients. Colloid-containing solutions, such as 5% and 25% albumin and hetastarch (6% hydroxyethyl starch), are second-line agents or the treatment o hypovolemia. They remain within the vascular compartment by virtue o their large molecular sizes. Hyperoncotic starch solutions should be avoided as they increase the risk o acute kidney injury, need or renal replacement therapy, and mortality. Hypovolemic shock may be accompanied by lactic acidosis due to tissue hypoper usion. Fluid resuscitation restores tissue oxygenation and decreases the production o lactate. Correction o acidosis with sodium bicarbonate has several potential adverse e ects, including increasing tonicity, worsening intracellular acidosis, and reducing ionized calcium concentration. There ore, its use to manage lactic acidosis in the setting o volume depletion is not recommended, unless the arterial pH is below 7.1.

■ EXTRACELLULAR FLUID VOLUME EXPANSION Excess extracellular uid accumulation usually results rom sodium and water retention by the kidneys. Renal sodium retention may be primary or a compensatory response to reduced e ective arterial blood volume. It mani ests clinically with edema and weight gain, commonly in response to congestive heart ailure (CHF), cirrhosis with ascites, or nephrotic syndrome. Renal sodium and water retention in CHF involves activation o the renin-angiotensin-aldosterone system (RAAS), as well as nonosmotic AVP stimulation, which drives the hyponatremia associated with CHF. Arterial under lling is also responsible or water and sodium retention in cirrhosis. Unlike CHF and cirrhosis, in which the kidneys are structurally normal, the nephrotic syndrome is characterized by kidneys that are unctionally impaired. Rarer causes o edema include drug-induced edema, which may be seen with ingestion o systemic vasodilators, such as minoxidil and diazoxide, dihydropyridine calcium channel blockers, and thiazolidinediones. Nonsteroidal anti-in ammatory drugs (NSAIDs) can exacerbate volume expansion in CHF and cirrhotic patients by decreasing vasoregulatory prostaglandins in the kidneys. Clinical manifestations Patients with le t heart ailure may present with exertional dyspnea, orthopnea, and paroxysmal nocturnal dyspnea, whereas patients with predominant right heart ailure or biventricular ailure may exhibit weight gain and lower-limb swelling. Physical examination may reveal JVP elevation, pulmonary crackles, a third heart sound, or peripheral edema in the ankles or sacrum. Nephrotic patients classically present with periorbital edema because o their ability to lie at during sleep. Patients with severe nephrotic syndrome may exhibit marked generalized edema with anasarca. Cirrhotic patients present with ascites and lower-limb edema consequent to portal hypertension and renal sodium and water retention. Physical examination may reveal stigmata o chronic liver disease, such as jaundice, spider angiomata, palmar erythema, Dupuytren contractures, and splenomegaly. Therapy Management o ECF volume expansion consists o treating the underlying cause and achieving negative sodium balance with dietary sodium restriction and diuretics. Moderate dietary sodium restriction (2-3 g/d; 86-130 mmol/d) should be instituted. Restriction

1984

o total uid intake is usually only necessary or hyponatremic patients. Medications that promote sodium retention, such as NSAIDs, corticosteroids, estrogens, and androgens, should be eliminated, i possible. Diuretics are the cornerstone o therapy to remove excess volume. Other measures can be used when the response to diuretics is inadequate. Extracorporeal uid removal by ultra ltration can be utilized in patients with acute decompensated heart ailure with renal insuf ciency or diuretic resistance. In cirrhosis, largevolume paracentesis with albumin in usion (6-8 g per liter o ascitic uid removed) can be employed. Interventions to shi t ascitic uid to a central vein, such as a transjugular intrahepatic portosystemic shunt, may reduce re ractory ascites and improve GFR and sodium excretion. Diuretics are the mainstay o therapy or edematous states. As ECF volume expansion in CHF and cirrhosis may be a compensatory mechanism or arterial under lling, a judicious approach is necessary to avoid a precipitous all in cardiac output and tissue per usion. Diuretics can be classi ed into ve classes, based on their predominant sites o actions along the nephron (Figure 242-1). They inhibit the reabsorption o sodium and an accompanying anion, usually chloride. The resultant natriuresis decreases the ECF. However, the time course o natriuresis is limited because renal mechanisms attenuate the sodium excretion. The most serious adverse ef ects o diuretics are electrolyte and acid-base disturbances. Loop diuretics increase the excretion o potassium, magnesium, and calcium. Thiazide diuretics have similar e ects on potassium and magnesium, but unlike loop diuretics, they decrease urinary calcium losses. Thiazide diuretics inter ere with urine-diluting mechanisms, and may there ore pose a risk o hyponatremia. Patients on diuretic therapy require electrolyte monitoring, and may need oral supplementation o potassium and magnesium. Addition o a potassium-sparing diuretic may need to be considered in patients with severe or recurrent hypokalemia. The volume depletion caused by thiazides and loop diuretics leads to increased tubular urate reabsorption, promoting hyperuricemia and gout. Ototoxicity may occur with large intravenous doses o loop diuretics, particularly when an aminoglycoside is coadministered. Gynecomastia may develop with spironolactone therapy. Long-term loop diuretic tolerance occurs as a consequence o hypertrophy o the distal nephron segment and enhanced sodium reabsorption rom increased exposure to solutes not absorbed proximally. This can be addressed by combining loop and thiazide diuretics, as the latter blocks reabsorption distal to the loop o Henle. Diuretic resistance re ers to edema that is or has become re ractory to a given diuretic. Diuretic resistance has several causes. Chronic kidney disease is associated with decreased secretion and tubular delivery o diuretics, reducing their concentration at the active site in the tubular lumen. Arterial under lling in cirrhosis and CHF is associated with diminished nephron responsiveness to diuretics because o increased proximal tubular sodium reabsorption, leading to decreased delivery o sodium to the distal sites o diuretic action. Nonsteroidal anti-in ammatory drugs block prostaglandin-mediated increases in renal blood ow, leading to sodium retention. Treatment o diuretic resistance includes salt restriction, increasing the dose o loop diuretics, administering more requent doses, and using combination therapy to sequentially block more than one site in the nephron, as that may result in a synergistic interaction between diuretics (Figure 242-2). In patients who respond poorly to intermittent doses o a loop diuretic, a continuous intravenous in usion can be tried. This has been associated with a better sa ety pro le but similar ef cacy in clinical trials. Ultra ltration may be necessary in highly resistant edematous patients. Table 242-2 lists e ective diuretic doses in patients with CHF, nephrotic syndrome, advanced cirrhosis, and renal ailure.

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Chronic re na l fa ilure

Ne phrotic syndrome

Mode ra te or s eve re CHF

Cirrhos is S pironola tone : Titra te up to 400 mh/d a s ne e de d. Cr Cl < 50 a dd

Cr Cl < 50

Loop diure tic: Titra te s ingle da ily dos e up to ce iling dos e a s ne e de d

Drop Thia zide

Mild CHF Cr Cl > 50 a dd

Cr Cl > 50

Thia zide : 50 to 100 mg/d HCTZ

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Loop diure tic: incre a s e fre que ncy of ce iling dos e a s ne e de d: furos e mide , up to 3 × da ily; Bume ta nide, up to 4 × da ily; Tors e mide, up to 2 × da ily

K+-s pa ring diure tic: If CrCl > 75 & urina ry [Na ]:[K] ra tio is < 1 (Note : May a dd K+-s pa ring diure tic to loop a nd/or Thia zide diure tic a t a ny point in a lgorithm for K+ home os ta s is.)

Add

Thia zide diure tic: CrCl > 50, us e 25 to 50 mg/d HCTZ CrCl 20 to 50, us e 50 to 100 mg/d HCTZ CrCl < 20, us e 100 to 200 mg/d HCTZ

While ma inta ining othe r diure tics, switch loop a ge nt to continuous infus ion Figure 242 2 Algorithm or diuretic therapy in patients with edema caused by renal, hepatic, or cardiac disease. (*For dosing details, see Brater DC. Diuretic therapy. N Engl J Med. 1998;339:387-395.) (Reproduced, with permission, rom Brunton LL, Lazo JS, Parker KL. Goodman &Gilman’s The Pharmacological Basis o Therapeutics, 11th ed. New York, NY: McGraw-Hill; 2006. Fig. 28-12.) 1985

TABLE 242-2 Therapeutic Regimens for Loop Diuretics in mg/d

Furosemide Bumetanide Torsemide

Moderate Oral IV 80-160 80 2-3 2-3 50 50

Severe Oral IV 240 200 8-10 8-10 100 100

Preserved Renal Function Nephrotic Syndrome Oral IV 240 120 3 3 50 50

Cirrhosis Oral IV 80-160 40-80 1-2 1 10-20 10-20

Congestive Heart Failure Oral IV 160-240 40-80 2-3 2-3 50 20-50

GFR, glomerular iltration rate; IV, intravenous.

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Ascites and edema in cirrhosis may be controlled by sodium restriction and diuretic therapy. The diuretic combination o urosemide and spironolactone, given in a ratio o urosemide 40 mg and spironolactone 100 mg daily to maintain optimal electrolyte balance, is more e ective than either drug administered alone. These drugs may be gradually titrated upward to a maximal dosage o urosemide 160 mg and spironolactone 400 mg daily.

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DISORDERS OF WATER BALANCE

■ HYPONATREMIA Hyponatremia (plasma sodium concentration below 135 mmol/L) is the most common electrolyte abnormality in hospitalized patients, occurring in 15% to 30% o medical inpatients, with over hal o cases being acquired during hospitalization. Most patients with hyponatremia have hypo-osmolar or hypotonic hyponatremia, with excess water in relation to solute. However, hyponatremia does not always signi y a hypotonic state. Rarely, patients have hypertonic hyponatremia, or translocational hyponatremia, due to osmotically active solutes that do not readily penetrate into cells, such as mannitol, contrast media, and sorbitol. To equalize osmolality across cell membranes, water shi ts out o cells to the extracellular space, leading to a drop in plasma sodium concentration. The most common cause is excess extracellular glucose, as in poorly controlled diabetes mellitus. Plasma sodium concentration alls by 1.6 mmol/L or every 100 mg/dL rise in the plasma glucose concentration. In pseudohyponatremia (isotonic hyponatremia), hyponatremia occurs when the solid phase o plasma, primarily lipids and proteins, is greatly expanded, as in hypertriglyceridemia and myeloma and other paraproteinemic disorders, leading to an arti actual decrease in plasma sodium concentration. Etiology and diagnosis Hypotonic hyponatremia is the most common plasma sodium disorder in the hospital setting, indicating an excess o water relative to sodium in plasma. This can occur with a decrease in total body sodium, or hypovolemic hyponatremia; a near-normal total body sodium, or euvolemic hyponatremia; or an excess o total body sodium, or hypervolemic hyponatremia (Figure 242-3). Since sodium is the primary cation in the ECF compartment, its concentration determines ECF volume. A comprehensive history and a physical examination ocused on the evaluation o the ECF volume allows or the classi cation o the hyponatremia into one o three categories: hypovolemic, euvolemic, or hypervolemic. In hypovolemic hyponatremia, de cits o both total body sodium and water lead to ECF volume depletion, with consequent AVP secretion and decreased solute- ree water excretion.

1986

Renal causes o solute-rich uid loss include diuretics, mineralocorticoid de ciency, salt-losing nephropathy, such as polycystic kidney disease and interstitial nephritis, and partial urinary tract obstruction. Fluid losses may also be extrarenal, especially gastrointestinal, such as gastroenteritis, peritonitis, pancreatitis, and ileus, as well as hemorrhage or excessive sweating. Historical eatures may include vomiting, diarrhea, diuretic use, thirstiness, or hyperglycemia with glucosuria. Physical examination may reveal tachycardia, orthostatic hypotension, and at neck veins. Help ul urinary studies include urine sodium and the Fe Na, which are typically less than 10 mmol/L and 1%, respectively with extrarenal uid losses. Urine sodium and Fe Na greater than 10 mmol/L and 1%, respectively, usually indicate renal losses, such as secondary to diuretic use and osmotic diuresis. In euvolemic hyponatremia, total body sodium content is generally normal, but there is hypo-osmolality rom a relative gain o water. Physical examination is notable or the absence o both eatures o volume overload, such as peripheral edema, ascites, pulmonary edema, and eatures o volume depletion, such as tachycardia, low blood pressure, or at neck veins. Concentrations o BUN and uric acid are normal or low, and the urine sodium is usually greater than 20 mEq/L. In this setting, hyponatremia is o ten due to the syndrome o inappropriate antidiuretic hormone secretion (SIADH), attributable to release o AVP rom the pituitary or, rarely, an ectopic source such as lung carcinoma. This leads to impaired water excretion, while the regulation o sodium balance is virtually una ected. Ingestion or administration o water is also required, since a high level o AVP alone is not usually suf cient to produce hyponatremia. Causes o SIADH include in ectious, in ammatory, neoplastic, and vascular disorders o the central nervous and respiratory systems, pain, narcotics, anticonvulsants, antidepressants, neuroleptics, and other drugs which act on the central nervous system (Table 242-3). However, in many hospitalized elderly patients with SIADH, the cause is obscure. Several entities should be considered prior to diagnosing SIADH. These include pro ound hypothyroidism, adrenal insuf ciency, renal impairment, and primary polydipsia. Hyponatremia may also be seen in excessive beer consumption (beer potomania), as beer is rich in carbohydrates and water, but poor in solutes and electrolytes. To make the diagnosis o SIADH (Table 242-4), patients must be euvolemic, and the urinary osmolality must exceed 100 mOsm/kg o water despite a low plasma osmolality (< 275 mOsm/kg o water). Because o the low urine volume in SIADH, the urinary sodium concentration is high, usually greater than 40 mmol/L, in the steady state. However, i the patient is volume depleted or on a saltrestricted diet, the urine concentration may be lower. Expanding the ECF volume with normal saline or normal salt intake increases urinary sodium, but does not correct the hyponatremia. Supportive laboratory tests or SIADH include hypouricemia (serum uric acid < 4 mg/dL) and low BUN (< 10 mg/dL). When the diagnosis is still uncertain, ECF volume depletion can be ruled out by in using 2 L

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Hyp e rto n ic hyp o n a tre m ia

S e rum glucos e S e rum lipids Tota l prote in

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Is ovo le m ic hyp o to n ic hyp o n a tre m ia

Hyp e rvo le m ic hyp o to n ic hyp o n a tre m ia

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Extrare nal lo s s Gl los s e s s (dia rrhe a , vomiting, NG s uction, pa ncre a titis ) S kin los s e s (burns, swe a ting) Lung los s e s Third-s pa cing Tra uma tize d mus cle Pos tdiure tic the ra py

Re nal lo s s Diure tics , os motic diure tics (ure a , ma nnitol, glucos e ) Urina ry obs truction Sa lt-los ing ne phritis Ke tonuria Bica rbona turia (RTA, me ta bolic a lka los is ) Adre na l ins ufficie ncy

Extrare nal Cirrhos is Conge s tive he a rt fa ilure Ne phros is

Re nal Acute re na l fa ilure Chronic re na l fa ilure

Wa te r intoxica tion (phychoge nic, ia troge nic) S IADH Ne opla s m Pulmona ry dis e a s e CNS dis e a s e Re s e t os mos ta t Pa in, e motion, pos t-op drugs Hypothyroidis m Pota s s ium los s Glucocorticoid de ficie ncy

Figure 242 3 Diagnostic algorithm or hyponatremia. (Adapted, with permission, rom Johnson RJ, Freehaly J, eds. Comprehensive Clinical Nephrology, 2nd ed. St. Louis, MO: Mosby; 2003.) o normal saline over 24 to 48 hours. Correction o hyponatremia, along with a drop in urinary osmolality, suggests volume depletion rather than SIADH. Caution must be exercised when administering saline to hyponatremic patients, because in a subset o patients this can induce brisk water diuresis and a rapid rise in serum sodium. Osmotic demyelination, with severe neurologic morbidity and even death, may occur with rapid correction o plasma sodium concentration (greater than 9 mEq/L rise in 24 hours) in patients with chronic hyponatremia. Frequent monitoring o serum and urinary electrolytes is thereore warranted. I rapid overcorrection occurs, administration o hypotonic uid or even AVP may be needed to halt the progressive rise in serum sodium.

In hypervolemic hyponatremia, both total body sodium and water are increased, but water is comparatively more so. Underlying causes include cardiac ailure and liver cirrhosis, in which the kidneys are intrinsically normal, but respond to decreased e ective arterial per usion with increased AVP levels and activation o RAAS. Acute and chronic kidney disease may be associated with hyponatremia i water intake exceeds the ability to excrete equivalent volumes. Hyponatremia is a risk actor or diminished survival in cardiac ailure and cirrhosis. In the absence o diuretics, Fe Na should be less than 1% in both conditions. However, a Fe Na greater than 1% is seen in the hypervolemic hyponatremic patient with acute or chronic kidney disease with tubular dys unction leading to suboptimal sodium and water absorption. 1987

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TABLE 242-3 Causes of the Syndrome of Inappropriate Antidiuretic Hormone Secretion Drugs • Antipsychotics • Antidepressants (tricyclics and SSRIs) • Narcotics • Anticonvulsants • Cytotoxic drugs (vincristine, cyclophosphamide, i os amide) • Nicotine • Clo ibrate • Nonsteroidal anti-in lammatory drugs • MDMA (ecstasy) Pulmonary disorders • Bacterial and viral pneumonia • Lung abscess • Bronchiectasis and cystic ibrosis • Tuberculosis • Aspergillosis • Mechanical ventilation with positive pressure Central nervous system disorders • Subdural hematoma • Subarachnoid hemorrhage • Stroke • Tumors • Meningitis, encephalitis, brain abscess • Vasculitis and other in lammatory disorders • Multiple sclerosis • Guillain-Barré syndrome • Hydrocephalus Malignancies • Small cell lung cancer • Head and neck cancer • Nonsmall cell lung cancer • Mesothelioma • Gastrointestinal adenocarcinoma • Genitourinary tract cancers • Leukemia Others • Postoperative stress • Pain • Nausea and vomiting • Endurance exercise • AIDS • Hereditary gain-o - unction mutation in the V2 receptor Note: The most common causes are listed in bold.

The clinical mani estations o hyponatremia are mainly neurologic and caused by intracellular uid shi ts, leading to brain swelling and edema. The severity o symptoms depends on the rate o decline o serum sodium concentration, because the adaptive mechanisms to protect brain cell volume require a longer time to be ully unctional. These mechanisms involve a gradual loss o potassium and organic solutes to restore cell volume to normal. Symptoms include nausea, vomiting, headache, lethargy, seizures, and a progressively decreased level o consciousness, ending in coma and 1988

TABLE 242-4 Criteria for the Diagnosis of the Syndrome of Inappropriate Antidiuretic Hormone Secretion Key features Decreased e ective osmolality (< 275 mOsm/kg o water) Inappropriately elevated urinary osmolality > 100 mOsm/kg o water despite hypotonicity Clinical euvolemia Urinary sodium > 20 mEq/L with normal dietary sodium intake Normal thyroid, adrenal, pituitary, and renal unction No recent diuretic use Supplemental features Plasma uric acid < 4 mg/dL Blood urea nitrogen < 10 mg/dL Fractional excretion o sodium > 1%; ractional urea excretion > 55% Failure to correct hyponatremia a ter in usion o normal saline Correction o hyponatremia through luid restriction

death. Neurologic signs o severe acute hyponatremia may include depressed deep tendon re exes, hypothermia, pseudobulbar palsy, and Cheyne-Stokes respirations. Psychiatric patients are at risk or hyponatremia or many reasons, including: • Thirst-producing anticholinergic side e ects o antidepressants

and antipsychotics • SIADH rom typical and atypical antipyschotics, tricyclic antidepressants, and selective serotonin reuptake inhibitors • Obsessive-compulsive behavior • Lack o satiety rom water consumption in patients hospitalized or alcoholism or anorexia Schizophrenic patients are particularly at risk: up to 14% have hyponatremia, and up to 25% have polydipsia. This predisposition may be multi actorial, relating to a decreased osmotic threshold or AVP release, enhanced renal sensitivity to AVP, and a de ect in the osmoregulation o thirst. Clozapine may have a lesser tendency to cause polydipsia and hyponatremia than other antipsychotics. Un ortunately, it has uncommon but severe adverse e ects, including agranulocytosis, seizures, myocarditis, and orthostatic hypotension.

PRACTICE POINT

• • •

SIADH and psychogenic polydipsia may be di erentiated based on the urine osmolality. In SIADH urine osmolality is ≥ 100 mOsm/kg. In psychogenic polydipsia it is < 100 mOsm/kg. Fluid restriction is the main treatment or psychogenic polydipsia, but is dif cult to en orce in practice. The antibiotic demeclocycline, which blocks the activity and action o AVP, may have some utility in treatment o psychogenic polydipsia.

Therapy Hypovolemic hyponatremia is treated with volume repletion with isotonic saline to expand ECF volume and interrupt AVP release. Volume expansion should be continued until blood pressure is restored and the patient demonstrates clinical euvolemia. When the initial volume estimate is equivocal, a uid challenge with 0.5 to 1 L o isotonic saline can be both diagnostic and therapeutic.

TABLE 242-5 Using Hypertonic Saline to Treat Acute Symptomatic Hyponatremia with Neurologic Symptoms • In use 3% hypertonic saline initially at 1-2 ml/kg/h. • For each 100 ml o 3% hypertonic saline, the serum sodium

concentration will increase approximately by 2 mmol/L. • Alternatively, in use a 100 mL bolus o 3% hypertonic saline over 10 min. Repeat twice at 30-min intervals i needed. • Monitor serum sodium level requently. • Discontinue hypertonic saline as soon as the patient is asymptomatic or less severe degree o hyponatremia has been attained (125-130 mmol/L).

C H A P T E R 2 4 2 D i s o r d e r s o S o d i u m a n d W a t e r B a l a

The treatment o hyponatremia in euvolemic patients depends on the degree o symptoms and on whether it has developed acutely (within hours) or chronically (over more than 48 hours). Acute hyponatremia with onset in the hospital is most o ten related to hypotonic solutions. The rapid development o hyponatremia with very low sodium values (< 110-115 mmol/L) may cause uid to shi t into brain cells, possibly leading to cerebral edema and death, as the adaptive changes cannot keep pace with intracellular uid shi ts leading to brain swelling within the con ned skull space. In acute severe hyponatremia with neurologic symptoms, the treatment o choice is 3% hypertonic saline, in used initially at 1 to 2 mL/kg/h (Table 242-5). For each 100 mL o 3% hypertonic saline, the serum sodium concentration will increase approximately by 2 mmol/L. This should be continued until a less severe level o hyponatremia has been attained (ie, 125-130 mmol/L), or symptoms resolve. I seizures, obtundation, or coma are present, hypertonic saline may be in used at 4 to 6 mL/kg/h or a short period o time. An alternative approach that has been success ully used in marathon runners is in using 100 mL bolus o 3% hypertonic saline, enough to increase the serum Na approximately by 2 mmol/L. A small, quick increase in the serum Na (2-4 mmol/L) is e ective in treating acute hyponatremia because reducing brain swelling even slightly will substantially decrease intracerebral pressure. I severe neurologic symptoms persist or worsen, or i the serum sodium is not improving, a 100-mL bolus o hypertonic saline can be repeated one or two more times at 10-minute intervals. When hyponatremia develops over several days, brain cells extrude organic solutes rom their cytoplasm, allowing intracellular osmolality and plasma osmolality to equalize without a large increase in cell water. Because o this rapid normalization o chronic hyponatremia may also lead to cerebral edema. Hyponatremia should be corrected very gradually when it has been present or more than 48 hours, or the duration is unknown. Serum sodium initially be increased by 4 to 6 mEq/L during the rst 24 hours and by less than 9 mEq/L over any given 24-hour period. It should be corrected even more slowly in high-risk patients with

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The treatment o hyponatremia in the context o volume overload requires management o the underlying cardiac ailure or liver cirrhosis. Sodium and water restriction as well as diuretics should be employed as necessary. When hyponatremia occurs, uid restriction to amounts less than insensible losses plus urine output is necessary to cause a negative solute- ree water balance, but is o ten di cult to achieve. Diuretic-resistant cases o CHF and liver cirrhosis may be treated with ultra ltration and large-volume paracentesis, respectively.

severe malnutrition, alcoholism, or advanced liver disease, who have an impaired ability to protect their intracellular volume by generating osmotically active molecules such as glycine, taurine, and myoinositol. Rapid correction o chronic hyponatremia, outpacing the brain’s ability to recapture lost organic osmolytes, may result in osmotic demyelination syndrome, which especially a ects glial cells o the brainstem. Patients improve initially as hyponatremia resolves, but within days develop new, progressive, and sometimes permanent neurologic de cits, including uctuating level o consciousness, quadriparesis, pseudobulbar palsy, ataxia, dysarthria, and locked-in syndrome. Magnetic resonance imaging (MRI) may show T2-weighted hyperintensities in the brainstem, especially the pons, consistent with demyelination. In patients with chronic asymptomatic hyponatremia, hypothyroidism and secondary adrenal insuf ciency should be sought and treated appropriately i present. Potentially responsible medications should be discontinued. Ideally, SIADH is treated with therapy directed against its underlying cause. However, i the cause cannot be identi ed or expeditiously treated, hyponatremia should be treated conservatively with uid restriction. To achieve negative water balance, daily uid intake must be signi cantly limited to less than the 24-hour urine output plus insensible losses. The maximum tolerated uid intake is proportional to the oral osmotic load, so adequate intake o dietary protein and salt should be encouraged. Many patients will nd the recommended degree o uid restriction intolerable and dif cult to comply with. Oral medications that may be help ul include urea (30 g/d), demeclocycline (300-600 mg twice daily), or lithium, but these therapies have poor tolerability, inconsistent responses, and signi cant toxicities. Recently, vasopressin receptor antagonists (vaptans) have been introduced or the treatment o hyponatremia. These agents act by increasing electrolyte- ree water excretion (aquaresis) and hence raising serum sodium concentration. Conivaptan, a combined V1 and V2 receptor antagonist, has been approved by the United States Food and Drug Administration (FDA) or 4-day intravenous use in the hospital setting to treat euvolemic and hypervolemic hyponatremia. However, there are insuf cient data to use conivaptan in the treatment o acute symptomatic hyponatremia at this time. Conivaptan might be considered particularly or those with moderate to severe hyponatremia and symptoms, but not seizures, delirium, or coma, which would warrant the use o hypertonic saline. The selective V2 receptor antagonist, tolvaptan, is orally active and has been approved by the FDA or euvolemic and hypervolemic hyponatremia. However, the FDA warns that tolvaptan should not be used in any patient or longer than 30 days, and should not be given to patients with liver disease, including cirrhosis. Increased thirst is seen in patients treated with vaptans and may limit the rise in serum sodium. Moreover, overly rapid correction o the hyponatremia may occur, which can lead to irreversible neurologic injury.

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Hypervolemic hyponatremia

Hyponatremia: Discharge Checklist • Have patient and amily been educated about signs and symp-

toms o hyponatremia? • Has the patient and amily been educated about any restrictions on uid intake, i necessary? I indicated, speci y total liquid intake, not only water. Aim or a uid restriction that is 500 mL/d below the 24-hour urine volume. • Do not restrict sodium or protein intake unless indicated. • I the patient is being discharged on a vaptan, ensure that treat-

ment is not taken beyond 30 days. • Have blood draws or electrolyte testing and outpatient ollowup been arranged or 1 to 2 weeks a ter discharge? 1989

Although not as common as hyponatremia, hypernatremia is not in requent in hospitalized patients, particularly those in intensive care units. Hypernatremia is always associated with hyperosmolality, as sodium salts are the major extracellular solutes. Hyperosmolality leads to an exodus o water rom cells to the extracellular compartment to maintain osmotic equilibrium, with a loss o intracellular volume and shrinkage o brain cells. The major de ense against sodium elevation is the stimulation o thirst and AVP, leading to increased water intake and retention. While AVP is important, thirst provides greater protection against hypernatremia. Thus, hypernatremia due to water loss occurs mainly in vulnerable patients with altered mental status and those who are unable to obtain water, such as in ants, the elderly, and the severely ill. Causes o hypernatremia are grouped into three categories, according to the total body sodium content as estimated by extracellular volume (Figure 242-4). Thus, the diagnostic approach to the hypernatremic patient hinges on the assessment o extracellular volume. The history should include a review o recent and current medications, vomiting, diarrhea, increased urinary losses (polyuria), recent uid intake, and the presence or absence o thirst. Physical examination must assess volume and neurologic status. In hypovolemic hypernatremia, there is a predominant loss o solute- ree water leading to elevation in the serum sodium concentration. This can occur either rom renal or extrarenal sources. Extrarenal losses include gastrointestinal causes, with diarrhea being more likely than vomiting to cause hypernatremia. Osmotic diarrhea, as induced by lactulose, malabsorption, and some in ectious

diarrheas, may result in water being lost in excess o sodium and potassium, leading to hypernatremia. Secretory diarrhea, in contrast, produces uid with electrolyte content similar to plasma, leading to loss o volume and potassium, but not hypernatremia. Insensible salt and water losses through evaporation rom the respiratory tract and sweat, brought on by ever or strenuous exercise in hot temperatures, may lead to hypernatremia, because o the hypotonic nature o the lost uid. The most common renal causes o sodium and water loss are loop diuretics and osmotic diuresis. Loop diuretics may lead to hypernatremia because they provoke loss o isotonic or hypotonic uid. Osmotic diuresis rom nonelectrolyte solutes, such as urea and glucose, causes hypernatremia by impairing tubular reabsorption o sodium and water. Most hypotonic uid losses do not cause hypernatremia, unless inadequate ree water is ingested or in used to replace the ongoing losses. Hence, these disorders usually also involve some component o inadequate uid intake. In hypervolemic hypernatremia, there is excess sodium in the extracellular compartment with extracellular volume expansion. This is usually seen in hospitalized patients who receive excess saline or sodium bicarbonate to treat metabolic acidosis, or those receiving enteral or parenteral eedings without adequate ree water administration. Euvolemic hypernatremia Loss o water without sodium increases uid tonicity, but usually does not result in clinically evident volume depletion because water is mainly distributed in the intracellular compartment. Euvolemic

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■ HYPERNATREMIA

Hype rnatre mia

Na + + H2 O de ficits

H2 O los s e s

Na + addition exces s

Hypo vo le mia Tota l body wa te r ↓ ↓ Tota l body Na +↓

Euvo le mia Tota l body wa te r ↓ Norma l body Na +

Hype rvo le mia Tota l body wa te r ↑ Tota l body Na +↑ ↑

RENAL LOS S ES Os motic a nd loop diure tics , pos tobs truction, intrins ic re na l dis e a s e

Is o-or hypotonic urine (Urina ry Na + >20 mEq/L)

EXTRARENAL LOS S ES De rma l (s we a ting, burns ) ga s trointe s tina l (dia rrhe a m fis tula s )

Hype rtonic urine (urina ry Na + 20 mEq/L)

Diure tics a nd wa te r re pla ce me nt

No rmo natre mia

Figure 242 4 Diagnostic and therapeutic approach to hypernatremia. (Reproduced, with permission, rom Schrier RW. Renal and Electrolyte Disorders, 7th ed. Philadelphia, PA: Wolters Kluwer; 2010.)

1990

Clinical manifestations Patients without perturbed neurologic status and with normal thirst mechanisms should complain o thirst. I allowed to progress, hypernatremia becomes associated with con usion, restlessness, irritability, and other neurologic mani estations o cellular dehydration and brain cell shrinkage. Clinical signs may include muscular twitching, hyperre exia and ataxia. Severe elevations o serum sodium may lead to ocal and grand mal seizures, intracerebral hemorrhage, and death. More severe symptoms and signs occur in patients with rapidly rising serum osmolality, extremely elevated serum osmolality, especially above 325 mOsm/kg, and at extremes o age, with the very young and the very old being most vulnerable. Hypernatremia developing over a longer period o time enables brain cells to undergo osmotic adaptation by generating osmolytes (idiogenic osmoles) to guard against cell shrinkage. While protective, they may nonetheless predispose the brain to edema i hypernatremia is corrected rapidly by avoring intracellular uid shi ts.

C H A P T E R 2 4 2 D i s o r d e r s o d i u m a n d W a l a n c

The estimated water de cit is the di erence between desired body water and actual body water. In this example, the administration o 5.5 L (50.5-45 L) should correct the water de cit and normalize the serum sodium concentration. In addition to estimated water de cit, estimated ongoing water losses during the time o repletion should be added. This includes 500-1000 mL/d o insensible losses, with larger amounts in ebrile or mechanically ventilated patients. Water replacement should be carried out gradually over hours to days, unless there is evidence that hypernatremia has evolved quickly. This is because water replacement needs to keep pace with the osmotic adaptation process by which the brain cells keep rom shrinking. Replacement also has to be tailored to the presence o neurologic symptoms and signs, which call or more rapid serum sodium correction. Acute symptomatic hypernatremia that developed over hours may be rapidly corrected, as the risk o cerebral edema is minimal. In patients with acute symptomatic hypernatremia, serum sodium should be lowered by 1 mmol/L/h. Once the patient is no longer symptomatic, the correction rate can be reduced to 0.5 mmol/L/h. Hypernatremia that has developed over more than 24 hours, or is o unknown duration, should be corrected with a maximal rate o 0.5 mmol/L/h. Hal o the water de cit should be replaced over the rst 24 hours, with the remainder over the ollowing 24 hours or longer. The cornerstone o central DI treatment is desmopressin (dDAVP), administered either nasally, intravenously, or subcutaneously. Patients with nephrogenic DI do not respond to exogenous desmopressin. Salt restriction and thiazide diuretics produce mild volume contraction, which helps to decrease urinary output. Nonsteroidal anti-in ammatory drugs also help reduce urine output. Patients with lithium-associated nephrogenic DI may bene t rom amiloride.

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Actual serum sodium × TBW 157 mmol/L × 45/L = = 50.5 L Desired serum sodium 140 mmolL

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Then, desired body water is calculated rom the ollowing ormula:

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Actual TBW = body weight × 60% (50% in women)

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blood pressure measurements, and urine output. Once euvolemia is established, urther uid therapy should be delivered to gradually correct tonicity in the orm o hypotonic (0.45%) saline. In rare patients who develop hypernatremia with extracellular volume expansion, loop diuretics may be employed. Ultra ltration may sometimes be needed to treat hypernatremia in patients with advanced renal impairment. In patients with hypernatremia without extracellular volume depletion or expansion, the total body sodium is unchanged, but there is a de cit o total body water. Water can be replaced either orally or parenterally with 5% dextrose in water (D5W) or 0.45% NaCl (hal -normal saline). The estimated uid de cit can be estimated by a ormula that uses total body water (TBW), because sodium concentration re ects tonicity in all body compartments. For example, a 75 kg man with a serum sodium concentration o 157 mmol/L would need water as estimated by the ollowing:

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hypernatremia occurs when there is loss o uid that is low in sodium and potassium salts. The classic example is diabetes insipidus (DI) rom either de ects in AVP production or release (central DI), a ailure o renal response to AVP (nephrogenic DI), or, rarely, rom rapid degradation o AVP by vasopressinase during pregnancy. Most patients with DI present with polyuria and polydipsia; hypernatremia is usually not present unless uid intake is inadequate. Central DI can be partial or complete. Causes include head trauma, brain surgery, and in ammatory, neoplastic, and in ltrative disorders o the hypothamalus and pituitary. However, no cause is identi ed in about hal o the cases. Nephrogenic DI is usually a congenital or acquired de ect o vasopressin V2 receptors or the vasopressin-dependent water channel (aquaporin 2). Acquired causes include medullary or interstitial renal disease, such as interstitial nephritis, polycystic kidney disease, partial urinary tract obstruction, and advanced chronic kidney disease. Hypercalcemia and hypokalemia may also cause nephrogenic DI, as well as various drugs that impair response to AVP, such as lithium. The various orms o DI must be di erentiated rom primary polydipsia in patients who present with polyuria. Urine sodium, volume, and osmolality should be measured to determine the integrity o the AVP-renal axis. The normal response to hypernatremia is increased AVP release, resulting in urine osmolality that can reach a maximum o 1000 mOsm/kg in normal young individuals, and above 500 mOsm/kg in elderly patients who usually have reduced responsiveness to AVP. Reduced urine osmolality indicates either impaired AVP release (central DI) or action (nephrogenic DI). The various orms o DI may be di erentiated rom primary polydipsia in patients with polyuria by per orming the water deprivation test, along with administration o AVP. An increase in urine osmolality with exogenous AVP is consistent with central DI, whereas lack o response suggests nephrogenic DI. With uid restriction leading to a 3% weight loss, patients with primary polydipsia should spontaneously increase their urine osmolality and will not increase their urine osmolality more with exogenous vasopressin. With partial central DI, uid restriction will not maximally stimulate AVP, thus a urther increase in urinary osmolality (>10%) will occur with exogenous vasopressin.

Hypernatremia: Discharge Checklist Therapy

• Have patient and amily been educated about signs and symp-

In hypernatremia with extracellular volume depletion, restoration o ECF volume is the primary therapeutic target. Isotonic saline is the uid o choice, and the volume and rate o administration should be guided by clinical parameters including pulse rate, orthostatic

toms o hypernatremia? • Are patients being discharged on gastric tube eedings also receiving ree water supplementation via the tube several times daily to prevent hypernatremia?

1991

• I the patient has diabetes insipidus, is the treatment appropriate

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or the orm. Central DI is treated with desmopressin (dDAVP) whereas salt restriction, thiazide diuretics and NSAIDS are use ul in the treatment o nephrogenic DI. • Have blood draws or electrolyte testing and outpatient ollow-

up been arranged or 1 to 2 weeks a ter discharge?

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SUGGESTED READINGS

1992

Brater DC. Update in diuretic therapy: clinical pharmacology. Semin Nephrol. 2011;31:483-494.

Ellison DH, Berl T. Clinical practice. The syndrome o inappropriate antidiuresis. N Engl J Med. 2007;356:2064-2072. Felker GM, Lee KL, Bull DA, et al. Diuretic strategies in patients with acute decompensated heart ailure. NEnglJ Med. 2011;364:797-805. Schrier RW, Bansal S. Diagnosis and management o hyponatremia in acute illness. Curr Opin Crit Care. 2008;14:627-634. Sterns RH. Disorders o plasma sodium: causes, consequences, and correction. N Engl J Med. 2015;372:55-65. Verbalis JG, Goldsmith SR, Greenberg A, et al. Diagnosis, evaluation, and treatment o hyponatremia: expert panel recommendations. Am J Med. 2013;126(10 Suppl 1):S1-42.

243

CHAP TER

Kidney Stones Navin R. Gupta, MD Bertrand L. Jaber, MD, MS

Key Clinical Questions 1

How are kidney stones diagnosed?

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How should kidney stones be managed in the inpatient setting?

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What medical therapies acilitate stone passage?

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When is urology or nephrology consultation indicated?

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What ollow-up and urther testing is appropriate a ter discharge?

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What drugs and dietary therapies provide secondary prevention o kidney stones?

EPIDEMIOLOGY Kidney stones in ict recurrent episodes o excruciating pain and signi cant morbidity on a substantial portion o the population, including many young and otherwise healthy individuals. In the United States, the current li etime incidence o nephrolithiasis is 13% or men and 7% or women. Without treatment, the 5-year recurrence rate ollowing an initial episode is up to 50%. A recent report rom the National Health and Nutrition Examination Survey or the period o 1994 to 2010 describes a 70% increase in prevalence o sel -reported kidney stones, extending across men and women o all age groups. Regional variations in the requency and nature o kidney stone disease exist within the United States, with an increased prevalence in the southeastern region o the country. This variation may be related to di erences in climate and sunlight exposure, as well as dietary habits and beverage consumption. Kidney stones develop more requently among Caucasians than A rican Americans. Stones in the upper urinary tract are requently seen in industrialized countries and are associated with a more a uent li estyle, including high animal protein consumption, gout, and components o the metabolic syndrome, including hypertension, impaired glucose tolerance, increased waist circum erence, high triglycerides, and low-high-density lipoprotein cholesterol. Bladder stones are more commonly seen in developing countries and more requently a ect individuals with a poor socioeconomic status. Patients with kidney stones typically present with renal colic, characterized by severe pain and autonomic symptoms such as lightheadedness, diaphoresis, nausea, and vomiting. The severity o symptoms o ten results in a visit to a hospital emergency room, o ten requiring hospitalization and absenteeism rom work. In the United States, kidney stones account or more than 2 million outpatient visits, over 600,000 emergency room visits, and approximately 0.4% o hospital admissions. Complications may arise, such as urinary tract obstruction and pyelonephritis, or the need or stone removal by instrumentation, surgery, or extracorporeal shock wave lithotripsy (ESWL). Patients with recurrent stone disease also have a heightened risk o chronic kidney disease. In the year 2000, the annual cost o kidney stones in the United States, including hospitalizations, pro essional charges, and lost productivity, was estimated at $5.3 billion. PATHOPHYSIOLOGY AND RISK FACTORS Kidney stones can orm rom several substances excreted in the urine, and requently consist o two or more di erent substances (Table 243-1). Calcareous (calcium oxalate, phosphate, or mixed) stones are by ar the most common, accounting or over 80% o kidney stones. Metabolic de ects leading to stone ormation include hypercalciuria in over 65% o cases, and less requently hyperuricosuria, hyperoxaluria, hypocitraturia, or some combination thereo . For a kidney stone to orm, the concentration o a dissolved salt must exceed its solubility in urine, a condition known as supersaturation. Supersaturation is avored by increased urinary excretion o stone- orming salts, optimal urinary pH (Table 243-2), and decreased urinary volume, which leads to increased urinary concentration. The presence o crystallization acilitators in the urine, such as uric acid, or the absence o crystallization inhibitors, such as citrate, also contributes to stone ormation.

1993

Type Calcium • Calcium oxalate • Calcium phosphate • Mixed Magnesium ammonium phosphate (struvite) Uric acid Cystine Miscellaneous

TABLE 243-3 Risk Factors for Kidney Stone Disease

Frequency (%) 70-88 36-70 6-20 11-31 6-20 6-17 0.5-3 1-4

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TABLE 243-1 Composition of Kidney Stones

Risk actors or kidney stone ormation can be divided into diet, stone-provoking conditions, stone-provoking drugs, and anatomic abnormalities. Dietary actors promoting nephrolithiasis include low uid intake, which promotes urinary supersaturation, high sodium and animal protein intake, which promote hypercalciuria, and high oxalate intake, which promotes hyperoxaluria. In addition, a amily history o kidney stones and a personal history o gout also increase the risk o kidney stone disease. Table 243-3 displays a selected list o stone-provoking conditions, stone-provoking drugs, and anatomic urologic abnormalities associated with stone disease. O note, roux-en-Y gastric bypass surgery, a common bariatric surgical procedure, is associated with increased intestinal absorption o oxalate and hyperoxaluria, resulting in a long-term risk o kidney stone ormation. Major stoneprovoking drugs include uricosuric agents, such as probenecid, losartan, and eno brate, carbonic anhydrase inhibitors, such as acetazolamide and topiramate, and the antiretroviral agent indinavir, which crystallizes in the urine. Oxalobacter formigenes and Lactobacillus spp. are intestinal bacteria that produce an oxalate-degrading enzyme. The resulting increased intestinal degradation o oxalate may protect against stone ormation. Lack o intestinal colonization with O. formigenes is prevalent in patients with recurrent calcium oxalate stones due to hyperoxaluria. CLINICAL PRESENTATION Patients with kidney stones most o ten present to the hospital with renal colic. Others present with a urinary tract in ection, impaired renal unction rom obstructive uropathy, or chronic kidney damage. Increasingly, incidental kidney stones are diagnosed on imaging studies in patients admitted to the hospital or other reasons. Typical renal colic begins with the acute onset o severe pain that awakens the patient rom sleep. Colic typically lasts or 1 to 4 hours, ollowed by gradual improvement. The patient may move ceaselessly, looking or a com ortable position, and may also su er rom nausea, vomiting, and sweating.

TABLE 243-2 Solubility of Stone-forming Salts According to Urinary pH Solute Urate Oxalate Phosphate Cystine

1994

Acid pH ↓ ↓ ↑ ↓

Alkaline pH ↑ ↑ or ↓ ↓ ↑

Stone-Provoking Conditions Calcareous stones Hypercalciuria Primary hyperparathyroidism Milk-alkali syndrome Sarcoidosis Tuberculosis Prolonged immobilization Hyperoxaluria Crohn disease Short gut syndrome Roux-en-Ygastric bypass surgery Hypocitraturia Laxative abuse Polycystic kidney disease Medullary sponge kidney Renal tubular acidosis Urate stones Hyperuricosuria Gouty diathesis Myeloproli erative disorders Ulcerative colitis Struvite stones Paraplegia Neurogenic bladder Recurrent urinary tract in ections Stone-provoking Drugs Oxaluric agent Vitamin C (high dose) Calciuric agent Vitamin D (high dose) Uricosuric agent Probenecid Losartan Feno ibrate Urinary alkalinizing agent Acetazolamide Topiramate Crystalluric agent Triamterene Sul onamides Indinavir Anatomic Abnormalities Medullary sponge kidney Horseshoe kidney Pyelocalyceal diverticulum Megacalyces Hydrocalyces Ureteropelvic junction obstruction Megaureter Bladder outlet obstruction Bladder diverticulum Urethral diverticulum

Kidney

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Ure te rope lvic junction

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Midure te r

C H A P T E R 2 4 3 K i d n e y S t o n

The initial workup o a patient with suspected renal colic includes a urinalysis, urine culture, limited blood work, and an imaging study. The urinalysis may reveal an acid pH (7.5), suggesting calcium phosphate stones in the setting o renal tubular acidosis, or struvite stones, associated with in ection with a urea-splitting bacteria such as Proteus or Klebsiella. Microscopic examination o the urinary sediment may reveal speci c crystals (Figure 243-2). Urate crystals can be rhomboid, needle shaped, or amorphous in shape (Figures 243-2A to C). Oxalate crystals can be dumbbell or cigar shaped (Figure 243-2D, calcium oxalate monohydrate) or envelope shaped (Figure 243-2E, calcium oxalate dihydrate). Phosphate crystals can be in a cof n-lid structure (Figure 243-2F, triple phosphate) or a granular precipitate (Figure 243-2G, amorphous phosphate). Cystine crystals are hexaedric and at (Figure 243-2H), and pathognomonic or cystinuria. A cyanidenitroprusside test resulting in purple-red discoloration o the urine con rms the presence o cystine crystals. A limited blood work panel or the evaluation o kidney stone disease includes serum electrolytes to evaluate or renal tubular acidosis; blood urea nitrogen and creatinine to assess kidney unction; calcium, albumin, and phosphorus to evaluate or primary

Conditions Associated with Pain Genitourinary system Acute pyelonephritis, testicular torsion, epididymitis, cystitis, urethritis, prostatitis, menstrual pain, pelvic in lammatory disease, ruptured ovarian cyst, ovarian torsion Musculoskeletal system Abdominal muscular pain, rib pain Gastrointestinal system Biliary colic, cholecystitis, gastritis, acute pancreatitis, peptic ulcer disease, appendicitis, acute diverticulitis Cardiovascular system Acute myocardial in arction, aortic aneurysm Miscellaneous Retroperitoneal ibrosis, herpes zoster, pleural pain Conditions Associated with Hematuria Acute glomerulonephritis, arteriovenous mal ormations, anticoagulant use, cystitis, prostatitis, neoplasia

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INITIAL DIAGNOSTIC EVALUATION

TABLE 243-4 Differential Diagnosis of Kidney Stone Disease

s

As shown in Figure 243-1, the anatomic site o the stone in the urinary tract in uences the radiation o the pain to di erent locations. Several conditions o the genitourinary, musculoskeletal, gastrointestinal, and cardiovascular systems may produce hematuria, back pain, or abdominal pain, mimicking kidney stones (Table 243-4).

hyperparathyroidism; and uric acid to evaluate or gout. An elevated serum creatinine may re ect acute kidney injury rom bilateral obstructive uropathy, unilateral obstruction in the setting o a single unctioning kidney, preexisting chronic kidney disease, extracellular uid volume depletion, or in ection. A urine culture should be obtained to rule out concomitant urinary tract in ection, particularly with the urea-splitting bacteria such as Proteus that lead to struvite stones. Fever should trigger a more thorough investigation or pyelonephritis and sepsis. The imaging modality o choice is a nonenhanced helical computed tomography (CT) scan, which has 98% sensitivity and 97% speci city or the diagnosis o kidney stones as small as 1 mm in diameter. O note, indinavir stones are radiolucent and undetectable by CT scan. Ultrasonography can only visualize the kidney and proximal ureter, detecting stones equal to or greater than 3 mm in diameter. Consequently, it has a sensitivity and speci city o 61% and 97%, respectively. However, due to the lack o radiation exposure, ultrasonography may have a role or pregnant women and children. An abdominal plain x-ray (ie, kidneys, ureters, and bladder x-ray) visualizes the entire urinary tract proximal to the urethra, detecting 90% o stones greater than 2 mm in diameter, but cannot detect radiolucent uric acid stones. TREATMENT OF AN ACUTE EPISODE

■ INITIAL EMERGENCY ROOM MANAGEMENT

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Ure te rove s ica l junction

Figure 243 1 Characteristics of renal colic according to stone location. (A) Stone at the ureteropelvic junction; mild dull to excruciating sharp pain in the flank, often radiating to the upper ipsilateral abdominal quadrant. (B) Stone in the midureter; pain radiating caudally and anteriorly toward the mid- and lower abdomen in a curved band-like fashion, initially parallel to the lower-costal margin, but then deviating caudally toward the bony pelvis and inguinal ligament. (C) Stone in the distal ureter; pain radiating into the scrotum or the tip of the penis in men, and associated with urinary frequency and urgency, dysuria, and gross hematuria.

Symptomatic treatment includes administration o intravenous or oral uids to acilitate stone passage, adequate pain control with nonsteroidal anti-in ammatory drugs or opioids, and antiemetics. Although parenteral ketorolac has been shown be as e ective as opioids or the treatment o renal colic, this drug should be used cautiously among patients with impaired kidney unction, as repeated doses may precipitate acute kidney injury. Nonsteroidal anti-in ammatory drugs have the added bene t o reducing ureteral in ammation surrounding the stone, thus acilitating stone passage. Antibiotics are not routinely recommended or kidney stone disease, unless there is concomitant in ection. To acilitate stone passage, both calcium channel blockers, such as ni edipine, and α-blockers, such as tamsulosin, have been shown to increase the likelihood o stone passage. In one study, 63% o physicians practicing in an emergency department used α-blockers or medical expulsive therapy. 1995

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Figure 243 2 Urinary crystal identification. Rhomboid (A), needle-shaped (B), or amorphous (C), urate; dumbbell-shaped or cigar-shaped calcium oxalate monohydrate (D), envelope-shaped calcium oxalate dihydrate (E), coffin-lid-shaped triple phosphate (F), or amorphous phosphate (G). (A-C, E-H: Reproduced, with permission rom Gra L. A handbook of routine urinalysis. Philadelphia: Lippincott, Williams & Wilkins, 1983.) (D: Reproduced rom Mor in and Chin. Urinary calcium oxalate crystals in ethylene glycol intoxication. N Engl J Med. 2005;353:e21. With permission rom the Massachusetts Medical Society. Copyright © 2005 Massachusetts Medical Society, all rights reserved.)

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PRACTICE POINT Medical expulsive therapy for kidney stones • Kidney stones irritate the lining o the ureter, producing pain and spasm. Ureteral spasm inter eres with peristalsis and decreases the likelihood o spontaneous stone passage. Calcium channel blockers and α-blockers at appropriate doses relax the distal ureter without abolishing peristalsis. This leads to a reduction in symptoms o colic and allows a greater chance o stone passage. The best-studied agents are the calcium channel blocker ni edipine, given at relatively low doses (30-40 mg daily), and the α-blocker tamsulosin, dosed at 0.4 mg daily. A 4-week trial o either agent may be reasonable or stable patients with distal ureteral stones measuring less than 10 mm. Both ni edipine and tamsulosin may cause orthostatic hypotension. Tamsulosin may be more e ective than ni edipine, but causes the additional side e ect o abnormal ejaculation in men. Corticosteroids and anticholinergics con er little additional bene it in patients already taking an α-blocker or calcium channel blocker.

■ INDICATIONS FOR HOSPITALIZATION Failure to control pain, impaired renal unction in the setting o obstructive stones, and suspected pyelonephritis with sepsis should trigger hospitalization. I the patient is likely to require a urologic intervention, the decision or hospitalization might be made on an individual basis in conjunction with the urology service. Figure 243-3 displays the diagnostic and treatment algorithm or an acutely symptomatic kidney stone.

■ UROLOGY CONSULTATION Stones larger than 5 mm are less likely to be expelled spontaneously than smaller ones (Table 243-5). Consequently, urologic consultation

1996

S us pe cte d Acute ly S ymptoma tic Kidne y S tone

• Exe cute Ima ging S tudy (Compute d Tomogra phy, Ultra s onogra phy) • Urina lys is • Urine Culture

Kidne y S tone Ide ntifie d? No Ye s • > 5 mm in dia me te r • Urina ry Obs truction • S e ps is of Urina ry S ource

Cons ide r Alte rna te Dia gnos is Ye s

No • Hydra tion (Intra ve nous a nd Ora l) • Alpha -blocke rs +/– Ca lcium Cha nne l Blocke rs • Ana lge s ics • S tra in Urine

S tone P a s s e d?

Urology Cons ult No

Ye s S e conda ry P re ve ntive Me a s ure s

Figure 243 3 Diagnostic and treatment algorithm for an acutely symptomatic kidney stone.

is warranted i the stone does not pass spontaneously, is larger than 5 mm in diameter, causes urinary obstruction, or is associated with urinary sepsis. I endourologic intervention becomes necessary, a variety o approaches can be employed, depending on the stone location. These include ureteroscopy with placement o a double J-stent or stones in the proximal ureter, basket stone retrieval or those in the distal ureter, and extracorporeal shock-wave lithotripsy or stones in the renal pelvis. Figure 243-4 displays a proposed urologic treatment algorithm according to size, location, and type o stone.

■ NEPHROLOGY CONSULTATION In-hospital nephrology consultation is advised in the setting o nonresolving acute kidney injury or advanced preexisting chronic kidney disease. Outpatient nephrology re erral may be warranted or secondary prevention, particularly among recurrent stone ormers, or rst stone ormers who have conditions or who take medications known to provoke stone ormation. (See below or a more detailed discussion o outpatient management.) LONG-TERM MANAGEMENT OF KIDNEY STONES

■ GENERAL CONSIDERATIONS In patients without risk actors or recurrent stone ormation (see Table 243-3), a simpli ed evaluation is usually suf cient. This consists

C H A P T E R 2 4 3 K i d n e y S t o

Unlikely to pass spontaneously. (Reproduced rom Teichman. Acute renal colic rom ureteral calculus. N Engl J Med. 2004;684-693. With permission rom the Massachusetts Medical Society.) *

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Likelihood of Need for Intervention (%) 3 14 50 99

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Size of the Stone ≤ 2 mm 3 mm 4-6 mm >6 mm *

Mean Days Until Passage 8 12 22 –

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TABLE 243-5 Likelihood of Passage of Ureteral Stones According to Size

o a dietary and medical history, review o the urinalysis, urine culture, helical CT scan, blood tests obtained during hospitalization, and a stone analysis, i available. Serum levels o parathyroid hormone and angiotensin-converting enzyme may be indicated i hypercalcemia is present. However, patients with recurrent stones and those with a positive amily history o stones or medical conditions associated with stone recurrence should have urther evaluation. Comprehensive evaluation includes keeping a dietary journal and completing a ood requency questionnaire. A 24-hour urine collection should also be per ormed, with measurement o creatinine (to con rm adequacy o collection), volume (to assess uid intake), calcium (to assess or hypercalciuria), oxalate (to assess or hyperoxaluria), uric acid (to assess or hyperuricosuria), citrate (to assess or hypocitraturia), and cystine (to assess or cystinuria). Additional 24-hour measurements include excretion o urinary sul ate, which re ects animal protein intake, urinary sodium, which promotes hypercalciuria i elevated, and magnesium excretion rate, which promotes stone ormation i low. Several 24-hour urinary collection kits are commercially available in the United States to assist in this metabolic evaluation. These also provide supersaturation indices pertaining to calcium oxalate, urate, and calcium phosphate precipitation in the urine.

■ SECONDARY PREVENTION Recommendations or secondary prevention o kidney stones are based largely on observational studies and a hand ul o randomized controlled trials. Diet and lifestyle modification Every kidney stone patient should have a high uid intake, at least 3 L/d, allowing or excretion o dilute urine throughout the entire day and night. To ensure dilute urine at night, patients must drink one to two eight-ounce glasses o water at bedtime, ollowed by another eight-ounce glass during the night, as a ter voiding. Un ortunately, requent nocturia limits adherence to this regimen, and daytime access to water during work hours might be dif cult or some patients. In addition to the total uid consumed, the type o beverage might also play a role. In middle-aged women, co ee, tea,

≤ 1 cm

ES WL (± S tone pus hba ck into re na l pe lvis )

> 1 cm

Flexible ure te ros copy + la s e r lithotripsy (or pe rcuta ne ous flexible ne phros copy)

Proxima l ure te ra l s tone

Midure te ra l s tone

Flexible ure te ros copy + la s e r lithotripsy (± ba s ke ting)

Dis ta l ure te ra l s tone

Flexible ure te ros copy + la s e r lithotripsy (or ES WL)

Fa ilure

• S ta ghorn ca lculi • Ana tomica l de fe cts • Morbid obe s ity

Re trope ritone a l la pa ros copy or ope n s urge ry

Figure 243 4 Urologic treatment algorithm according to size, location, and type of kidney stone. ESWL, extracorporeal shock-wave lithotripsy.

1997

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and wine intake has been shown to be independently protective, whereas grape ruit juice has been shown to promote kidney stones. These ndings were con rmed in men, with the additional nding that the risk o kidney stones was reduced by beer and increased by apple juice. While strongly hopped beers such as European lagers may contain signi cant amounts o oxalate, which increases kidney stone risk, beer consumption also increases urinary ow and dilution, likely explaining their neutral or even bene cial e ects in observational studies. Dietary sodium restriction to less than 2 g/d should also be recommended to all patients, as high sodium intake increases urinary calcium excretion and acilitates calcium stone ormation. Dietary calcium intake has variable e ects on stone ormation. Excess calcium intake, especially i combined with vitamin D3 supplementation, invariably leads to increased calcium absorption and hypercalciuria. However, dietary calcium restriction reduces enteral chelation o dietary oxalate, acilitating oxalate absorption and subsequent urinary excretion, and increasing the risk o recurrent calcium oxalate stones. Calcium restriction also leads to loss o bone mass and a higher likelihood o osteoporosis. Experts recommend avoidance o extremes o calcium intake, and remaining within the recommended daily allowance (RDA) or calcium o 800 to 1000 mg/d. Patients with calcium oxalate stones should limit daily intake o animal protein to 0.8 g/kg o body weight, which is the RDA. High-protein diets increase urinary calcium excretion because the amino acids, methionine, cysteine, and cystine, oxidize sul ur to sul ate, which is excreted with calcium to maintain electroneutrality. Dietary oxalate restriction is recommended in oxalate stone ormers. Foods with high oxalate content include peanuts, tea, instant co ee, rhubarb, beets, beans, berries, chocolate, spinach and other dark lea y greens, oranges, to u, sweet potatoes, and dra t beer. (The high oxalate content o co ee, tea, and beer is negated by their diuretic e ects.) Foods with a high purine content, such as red meat, organ meats, beer, and cruci erous vegetables, such as broccoli and cauli ower, increase urinary uric acid excretion and should be restricted in those with uric acid stones. For indinavir-associated kidney stones, which occur in 10% to 15% o patients a ter 6 months o therapy initiation, the drug should be temporarily or permanently discontinued. On urine sediment, indinavir crystals have a starry appearance. Indinavir stones tend to be radiolucent on CT scan and are best detected by ultrasound.

In enteric hyperoxaluria due to malabsorption, as in in ammatory bowel disease, dietary oxalate restriction should be initiated. I this is unsuccess ul, a low- at diet, calcium carbonate supplements, medium-chain atty acid supplementation, and enteralbinding therapy with cholestyramine can be attempted alone or in combination. Hypocitraturia warrants potassium citrate supplementation, at a minimum dose o 40 to 60 mEq/d in two to three divided doses. Sodium-based citrate ormulations should be avoided, due to their high sodium content. In calcium phosphate stones, citrate supplementation should be used with caution, since excessive urinary alkalinization might promote calcium phosphate precipitation. In hyperuricosuria, in addition to reducing purine intake, potassium citrate supplementation is use ul to alkalinize the urine and maximize urate solubility. I citrate alone cannot consistently raise the urine pH, an evening dose o acetazolamide may be added. Allopurinol and ebuxostat, two xanthine oxidase inhibitors, are equally e ective in preventing recurrent calcium-containing stones in patients with hyperuricosuria. Cystinuria is a rare inherited tubular disorder o amino acid transport that leads to increased excretion o cystine, as well as ornithine, lysine, and arginine, which do not orm stones. This autosomal recessive disorder has a prevalence o 1 in 7000. Patients develop symptoms rom cystine stones beginning in the second and third decades o li e. Cystine stones are extremely hard and resistant to ESWL. Patients are also prone to develop calcium oxalate stones, rom associated hypercalciuria, hyperuricosuria, and hypocitraturia. Urinary cystine solubility is pH-dependent, and urine alkalinization is the mainstay o treatment. In mild-to-moderate cystinuria, treatment consists o mild sodium restriction, potassium citrate supplementation to alkalinize the urine pH, and high uid intake. The patient should keep a log o urinary pH results to sel -monitor therapy. Captopril or tiopronin, which orms soluble complexes with cysteine, should be given in more severe cystinuria. In recurrent struvite stones, the chronic use o suppressive antibiotics or urease inhibitors such as acetohydroxamic acid may be considered. All dietary and pharmacologic interventions should be ollowed up with a repeat 24-hour urine collection 3 to 6 months a ter the intervention in order to monitor treatment success and adherence.

Drug therapy

Kidney stone disease is a common and debilitating urinary tract disorder, with a li etime risk o ~10% and a 5-year recurrence rate o 50%. First-time stone ormers without risk actors or recurrence require a limited evaluation. However, recurrent stone ormers as well as rst-time stone ormers with risk actors or recurrence require a more extensive evaluation. Dietary interventions and li estyle changes are uni ormly recommended, but the remainder o the therapy is o ten tailored to speci c metabolic and urinary abnormalities identi ed in the diagnostic evaluation. The long-term commitment and adherence to dietary and li estyle changes and pharmacologic treatment remains a challenging task.

In recurrent stone ormers, speci c pharmacologic therapies should be added or secondary prevention. For calcareous stones, i hypercalciuria is present, high-dose thiazide diuretics have been shown to be consistently e ective, in conjunction with a low-sodium diet. Options include hydrochlorothiazide (up to 50 mg twice daily) and chlorthalidone (12.5-100 mg/d). Amiloride combined with hydrochlorothiazide (10 mg/50 mg combination pill twice daily) has been used in an e ort to minimize hypokalemia. Patients with calcium oxalate stones, who have hyperuricosuria and normocalciuria, have been shown to bene t rom the use o allopurinol (300 mg daily). Unproven therapies to prevent calcium oxalate stones include magnesium and pyridoxine (vitamin B6). Magnesium enhances the solubility o urinary oxalate. In clinical trials, magnesium oxide and magnesium hydroxide are ine ective in stone prevention, but there may be a bene t o potassium magnesium citrate. Pyridoxine supplementation may reduce oxalate production, and large doses are associated with a reduced risk o stone ormation in women in observational studies. Another promising therapy or calcium oxalate stone ormers with hyperoxaluria is oxalatemetabolizing probiotic microorganisms, such as Lactobacillus species or O. formigenes. 1998

CONCLUSION

DISCHARGE CHECKLIST • Has pain control been achieved? • Is renal unction stable? • Has a decision been made regarding the need or urologic

intervention? • For patients who have not passed a stone at the time o hospital discharge: has a strainer been provided to retrieve a stone, in case o spontaneous expulsion? Is the patient being discharged on medical therapy to aid stone expulsion? (Tamsulosin is typically given or 4 weeks or until the stone has passed.)

Bao Y, Wei Q. Water or preventing urinary stones. Cochrane Database Syst Rev. 2012(6):CD004292. Fink H, Wilt T, Eidman K, et al. Medical management to prevent recurrent nephrolithiasis in adults: a systematic review or an American College o Physicians clinical guideline. Ann Intern Med. 2013;158:535-543.

C H A P T E R 2 4 3 K i d n e y S

Qaseem A, Dallas P, Forciea M, et al. Dietary and pharmacologic management to present recurrent nephrolithiasis in adults: a clinical practice guideline rom the American College o Physicians. Ann Intern Med. 2014;161:659-667.

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Pearle M, Gold arb D, Assimos D, et al. Medical management o kidney stones: American Urological Association Guideline. J Urol. 2014;192:316-324.

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Mor n J, Chin A. Images in clinical medicine. Urinary calcium oxalate crystals in ethylene glycol intoxication. N Engl J Med. 2005;353(24):e21.

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SUGGESTED READINGS

Hollingsworth JM, Rogers MA, Kau man SR, et al. Medical therapy to acilitate urinary stone passage: a meta-analysis. Lancet. 2006;368(9542):1171-1179.

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cation? All stone ormers should be counseled to minimize their sodium intake, and increase their uid intake. Patients known to have oxalate stones should be instructed about limiting their intake o animal protein and oxalate; urate stone ormers should be counseled about decreasing their purine intake; and a thiazide diuretic should be considered in patients known to have hypercalciuria. • Has outpatient ollow-up with urology been arranged? (This is usually indicated, especially i an outpatient procedure is being contemplated.) • Has nephrology ollow-up been arranged or patients who are recurrent stone ormers, or otherwise at high risk or recurrence?

Gold arb DS, MacDonald PA, Gunawardhana L, et al. Randomized controlled trial o ebuxostat versus allopurinol or placebo in individuals with higher urinary acid excretion and calcium stones. Clin J Am Soc Nephrol. 2013;8(11):1960-1967.

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• Has the patient been counseled about diet and li estyle modi -

Smith-Bindman R, Aubin C, Bailitz J, et al. Ultrasonography versus computed tomography or suspected nephrolithiasis. N Engl J Med. 2014;371:1100-1110. Teichman JM. Clinical practice. Acute renal colic rom ureteral calculus. N Engl J Med. 2004;350:684-693.

1999

244

CHAP TER

Secondary Hypertension William J. Elliott, MD, PhD

Key Clinical Questions 1

Which patients should be evaluated or secondary causes o hypertension in the inpatient setting?

2

What are the most common secondary causes o hypertension in hospitalized patients?

3

What screening and diagnostic tests are best or each?

4

What speci ic therapy or therapies are currently recommended?

5

What ollow-up should be recommended a ter discharge?

INTRODUCTION Hypertension a ects 29% o the American public, and a greater proportion o hospital inpatients. Hospitalized patients are older than the general population; the prevalence o hypertension is 65% in those aged 60 years and older, and 77% in those aged 80 years and older. In addition, hypertension is a major risk actor or cardiovascular and renal diseases that lead to inpatient admission. Poorly controlled hypertension among general medical inpatients is most o ten related to other conditions, such as pain, agitation rom delirium, and substance withdrawal. Secondary hypertension has a prevalence o less than 5% in the general population, but is more common among inpatients. This is due to three types o selection bias: (1) negative screening or secondary hypertension in outpatients, who are seldom hospitalized or evaluation and are at low risk o hospitalization or other causes; (2) patients admitted or hypertensive emergencies; and (3) patients with secondary hypertension admitted or diagnostic and therapeutic procedures, o ten or other diagnoses. For example, 13% o patients undergoing cardiac or peripheral arterial catheterization have a documented stenosis in a renal artery (discovered during “drive-by angiograms”). Secondary causes o hypertension should at least be considered in hypertensive inpatients, especially younger ones, ensuring that these patients are assessed at least once or secondary hypertension during their li etime. In addition, some causes are curable or at least amenable to intervention, such as pheochromocytoma, Conn adenoma, and bromuscular dysplasia. This may obviate the need to take long-term antihypertensive medications, improving the cost-e ectiveness o screening young patients.

PRACTICE POINT

•

A workup or secondary hypertension should be per ormed in all patients admitted to the hospital with a primary diagnosis o hypertensive urgency or hypertensive emergency, i not previously done.

CRITERIA FOR HOSPITAL ADMISSION Secondary hypertension leads to hospital admission when there is a hypertensive emergency (severely elevated blood pressure and acute, ongoing target-organ damage). See Chapter 91. These patients have a high prevalence o secondary hypertension, and the hypertensive emergency is o ten the rst real clue to the presence o a secondary cause. A ter stabilization o these patients with short-acting, intravenous antihypertensive drugs, attention should be ocused on developing an appropriate antihypertensive drug regimen and excluding secondary hypertension.

PRACTICE POINT

•

2000

There are many reasons why a hospitalized patient may have severe hypertension, including pain, uid overload, ragmentary knowledge o the patient’s home medications, and drug and alcohol withdrawal. Clinicians should seek out precipitating actors that commonly raise blood pressure in the acutely ill and may require a di erent approach rom simply prescribing antihypertensive medications.

C H A P T E R 2 4 4 S e c o n d a r y H y p e r t e n

Inpatient management

The most common secondary causes o hypertension in hospitalized patients are listed in Table 244-1. Note that the most common type o hypertension in hospitalized patients is still primary ( ormerly essential) hypertension.

Continuous positive airway pressure (CPAP) has been shown to reduce 24-hour ambulatory systolic and diastolic blood pressure, and especially nocturnal blood pressure, in individuals with sleep apnea. Hypertensive individuals with proven sleep apnea should be treated with a trial o CPAP. There is some evidence that aldosterone antagonists such as spironolactone may have bene cial e ects in reducing hypertension and apneic events in OSA.

■ SLEEP APNEA

■ CHRONIC KIDNEY DISEASE

Evaluation

Evaluation

An underappreciated piece o collateral damage rom the obesity epidemic is that sleep apnea has probably become the most

This secondary cause o hypertension di ers rom others in at least two respects: it is usually not remediable, and it may be both a

CLINICAL SYNDROMES

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A primary diagnosis o hypertensive crisis—a surge in blood pressure accompanied by acute, ongoing, end-organ damage— or a hypertensive urgency—a surge in blood pressure without such end-organ damage—may be the rst clue to the presence o secondary hypertension. A ter stabilization o these patients with short-acting, intravenous antihypertensive drugs and initiating an appropriate antihypertensive drug regimen, secondary causes o hypertension should be considered, especially in younger patients.

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PRACTICE POINT

common cause o resistant hypertension. Hypertension in obstructive sleep apnea (OSA) results rom multiple mechanisms. Hypoxia and hypercarbia are potent stimulators o sympathetic tone, and also contribute to oxidative stress and endothelial dys unction. The abrupt decrease in intrathoracic pressure during apneic episodes raises le t ventricular wall pressure and myocardial oxygen demand, contributing to atherosclerosis and le t ventricular hypertrophy. Recurrent episodes o arousal lead to sleep ragmentation, stress, and urther increases in sympathetic tone and catecholamine levels. Aldosterone levels are o ten high in patients with OSA, likely due in part to increased sympathetic tone. Edema rom aldosteronemediated sodium retention may shi t nocturnally rom the legs to the neck, increasing upper airway resistance and aggravating OSA. OSA should be suspected in hypertensive patients with obesity and daytime sleepiness. Patients and partners should be asked about snoring and witnessed apneic events. A sleep study (polysomnography) should be obtained, either in the inpatient or outpatient setting. Overnight pulse oximetry to look or requent nocturnal desaturations may be use ul to screen or OSA in the inpatient setting, when a sleep study cannot be obtained. It is reasonable to measure thyrotropin (TSH) levels in suspected OSA, i this has not recently been done.

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Occasionally, secondary hypertension becomes an issue in patients admitted or diagnostic or therapeutic procedures only indirectly related to hypertension. Examples include hypertensive patients with incidentally discovered adrenal masses, individuals who have incidental or “drive-by” renal angiograms a ter a planned coronary or carotid catheterization, and patients with an increase o greater than 25% in serum creatinine a ter administration o an angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB). Hospitalists caring or these patients should pursue appropriate diagnostic evaluation and treatment o secondary hypertension be ore discharge.

TABLE 244-1 Common Secondary Causes of Resistant Hypertension Diagnosis Sleep apnea

Primary hyperaldosteronism Renovascular hypertension Drug and alcohol abuse

Chronic kidney disease Cushing syndrome

Pheochromocytoma

Coarctation o the aorta

Key Features Daytime somnolence, loud snoring and breathing cessation during sleep, morning headache Hypokalemia, sleep apnea symptoms, resistant hypertension Abdominal bruit, “bump” in serum creatinine a ter ACE inhibitor or ARB Multiple mechanisms, including high sympathetic tone, vasoconstriction, endothelial dys unction eGFR < 60 mL/min/1.73 m 2, albumin/creatinine ratio > 300 µg/mg Hypertension, hyperglycemia, abdominal striae, proximal muscle weakness, hirsutism Hypertension, hyperhidrosis, headache (o ten in paroxysms) Blood pressure di erences across limbs; systolic murmur posteriorly

Risk Factors Obesity, age

Relative Prevalence 60%-70%

Screening Tests Sleep study

Sleep apnea

7%-20%

Aldosterone/renin ratio

Young women ( ibromuscular 2%-24% disease); atherosclerotic disease in older smokers Cocaine, methamphetamine, 2%-4% heavy alcohol use

Hypertension, diabetes

1%-2%

Women (Cushing disease); men (ectopic corticotropin production) Phakomatoses, multiple endocrine neoplasia syndromes Turner syndrome; other congenital arterial anomalies

< 1%

< 1%

< 1%

Doppler ultrasound

History, toxicology screen

Serum creatinine, irst morning voided urine or albumin-to-creatinine ratio Urinary ree cortisol; midnight serum (or salivary) cortisol Plasma metanephrines vs 24-h urine or VMA and metanephrines Echocardiogram (especially the sternal notch view)

ACE, angiotensin-converting enzyme; ARB, angiotensin receptor blocker; VMA, vanillylmandelic acid. Prevalence data rom JAMA. 2014;311(21):2216-2224.

2001

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cause and a consequence o hypertension. Chronic kidney disease is de ned as 3 months or more o an estimated glomerular ltration rate (eGFR) o less than 60 mL/min/1.73 m 2, or kidney damage de ned as pathologic abnormalities, abnormal imaging studies, or elevated blood or urine markers o kidney injury (usually albuminuria > 30 µg/mg creatinine in a rst-morning voided urine specimen). In large population-based studies, more advanced chronic kidney disease is linked to greater risks o death and hospitalization. As a result, this secondary cause o hypertension is thought to be about 5- to 10- old more common in hospitalized patients than in the general US population. Testing or chronic kidney disease is part o the admitting process or essentially every inpatient, with a serum creatinine (and in most hospitals, a calculated eGFR, based on the most recent update o the Modi cation o Diet in Renal Disease, or the Chronic Kidney DiseaseEpidemiology Collaboration, equations) and a urinalysis. Occasionally, the urinalysis can be alsely negative or protein i per ormed on a very dilute sample. I this is suspected, a rst-morning voided urine specimen should be obtained to measure the albumin-tocreatinine ratio. Inpatient management Intensive lowering o blood pressure is an e ective means to prevent or delay the progression o chronic kidney disease to endstage renal disease. Most authorities recommend that patients with chronic kidney diseases should have requent urinalyses and determinations o eGFR, and an ACE inhibitor or an ARB as part o their medication regimen, i possible. A lower-than-usual blood pressure goal (eg, < 130/80 mm Hg) has not improved outcomes in 3 clinical trials, but is still “suggested” (a weaker option than “recommended”) by the Kidney Disease: improving Global Outcomes (KDIGO) 2012 clinical practice guideline.

■ PRIMARY HYPERALDOSTERONISM Evaluation The clinical presentation o primary hyperaldosteronism is nonspeci c. Patients are occasionally diagnosed because o hypertension with spontaneous hypokalemia, or more severe hypokalemia on diuretic therapy than expected, but most patients with primary hyperaldosteronism are not hypokalemic. Primary hyperaldosteronism is more commonly recognized now than in the past, probably because o the widespread use o the plasma aldosterone/plasma renin ratio as a screening test in patients with re ractory hypertension. In older series, primary hyperaldosteronism was ound in only 0.1% to 0.5% o hypertensive patients, with most patients having hypokalemia and aldosteroneproducing adrenal adenomas (Conn syndrome). While the exact prevalence and signi cance o primary hyperaldosteronism in hypertension remains unclear, this is almost certainly an underestimate. Some studies have ound primary hyperaldosteronism in up to 5% to 10% o hypertensive patients, and in patients with resistant or re ractory hypertension, the prevalence may be as high as 11% to 23%. In recent series, 35% o cases were due to aldosteroneproducing adenomas, 60% were due to bilateral adrenal hyperplasia, and the rest were due to adrenal carcinoma, unilateral adrenal hyperplasia, glucocorticoid-remediable hyperaldosteronism, and other causes. The renewed interest in primary hyperaldosteronism also stems rom the availability o new therapies, such as laparoscopic adrenalectomy, and evidence that primary hyperaldosteronism has morbidities in addition to hypertension. Compared with patients with essential hypertension and similar levels o blood pressure elevation, patients with primary hyperaldosteronism are at higher risk o le t ventricular hypertrophy, diastolic dys unction, myocardial in arction, atrial brillation, stroke, albuminuria, and metabolic syndrome. As noted above, 2002

hyperaldosteronism seems to be especially common in obesity and sleep apnea. Possible explanations include renin release due to sympathetic nervous system activation during apneic episodes, adipocyte production o angiotensinogen, and aldosterone release driven by oxidized atty acids. The currently recommended initial screening test or primary hyperaldosteronism is the plasma aldosterone/plasma renin ratio, or ARR (Figure 244-1). A sample is drawn rom a patient who has been seated quietly or at least 15 minutes. Generally no changes are necessary in dietary salt intake or antihypertensive medications, except aldosterone antagonists, which should be stopped. Inhibitors o the renin-angiotensin system (including β-blockers) can improve the diagnostic per ormance o the test and may account or some o the controversy surrounding its use. In properly selected patients, an ARR o 20 to 40 (when the plasma renin activity is expressed in ng o angiotensin II/mL/h, and the aldosterone level in ng/dL) raises the suspicion o primary hyperaldosteronism. Similarly, the utility o the ARR is inversely proportional to the plasma-renin activity, as very low levels (eg, < 0.2 ng/mL/h, as a possible consequence o a high-sodium diet, or low-renin hypertension) increase the ARR exponentially. An elevated ARR is typically ollowed by one o our con rmatory tests, usually on the next hospital day. Clinicians generally pre er measuring plasma aldosterone be ore and a ter either saline in usion (2 L over 4 hours), or oral captopril (25 mg given 2 hours earlier), because both the udrocortisone suppression (0.1 mg every 6 hours or 4 days) and oral sodium loading (12 gm daily or 4 days) tests require too long a preparation period. The challenges with these tests involve the risk o hypotension with captopril, or volume overload with saline loading. I the patient is young or has a amily history o hyperaldosteronism, a morning sample o plasma or 18-hydroxycortisol and 18-oxo-cortisol levels may be help ul, as low or normal levels e ectively rule out glucocorticoid-remediable aldosteronism (which accounts or less than 1% o primary hyperaldosteronism in most series). Inpatient management I con rmatory testing shows no evidence o aldosterone suppression, a decision must be made about the risks and bene ts o possible surgery. Many avor simply treating such patients with aldosterone antagonists, as most (about two-thirds) will not have surgically remediable tumors. Should laparoscopic surgery be available and the patient and physician agree, an adrenal CT scan may be per ormed. I there is a unilateral hypodense (< 10 Houns eld units) nodule larger than 1 cm, most patients under the age o 40 years are o ered surgery. I the patient is older than 40 years or has a high clinical probability o a tumor and either normal adrenals, micronodularity, or bilateral masses, adrenal venous sampling is rst per ormed to localize the aldosterone-producing adrenal adenoma, be ore surgery. Otherwise, the patient is treated with an aldosterone antagonist. Spironolactone is less costly, but eplerenone has ewer adverse e ects. Laparoscopic adrenalectomy is the pre erred surgical approach because o lower rates o morbidity and shorter hospital stays. Cure rates o 56% to 77% have been cited, although eukalemia may be delayed or several days, and complete normalization o blood pressure (< 140/90 mm Hg without drug therapy) occurs in only about one-third. Because o the reduced medication burden (including adverse e ects and potassium supplementation and its monitoring), and improved blood pressure, adrenalectomy is said to be less expensive than medical therapy. For patients with hyperaldosteronism and a positive Berlin questionnaire suggestive o sleep apnea, re erral to a sleep center or polysomnographic testing is appropriate. Many o these patients will have improved blood pressure control on an aldosterone antagonist.

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Figure 244 1 Suggested diagnostic algorithm for most patients with suspected primary aldosteronism.

PRACTICE POINT

•

Most patients with primary hyperaldosteronism do not have hypokalemia.

■ RENOVASCULAR HYPERTENSION Evaluation Renovascular hypertension should be suspected in young women with the new onset o dif cult-to-treat hypertension, who are at risk or bromuscular dysplasia o the renal artery, or older patients with severe hypertension and known atherosclerotic disease elsewhere. Additional clinical clues to the diagnosis o renal artery stenosis include an epigastric bruit, acute kidney injury a ter starting an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker, and unexplained ash pulmonary edema. As the population ages and survival a ter acute myocardial in arction and other mani estations o atherosclerotic vascular disease has improved, renovascular hypertension has become more widely recognized. Un ortunately, the diagnosis and treatment o this condition are still controversial. Four recent clinical trials have shown little (i any) bene t to routine angioplasty, compared with chronic antihypertensive drug therapy. The prevalence o renal artery stenosis on angiography in hospitalized patients undergoing cardiac catheterization is as high as 39%, but many o these patients were not hypertensive. The pretest probability o renovascular hypertension can be calculated based on a patient’s presenting clinical characteristics (Table 244-2). This clinical prediction rule correctly identi es most patients with either a very high (> 70%) or very low (< 15%) probability o renovascular hypertension who do not require additional testing (Figure 244-2). Be ore embarking on a series o diagnostic

tests, two important questions should be answered. I the patient re uses vascular surgery, as might become necessary in the event o renal artery per oration during angioplasty or stenting, no urther diagnostic evaluation is recommended. The more dif cult question is whether an invasive intervention is indicated. Because all our trials comparing percutaneous angioplasty and medical therapy have shown no long-term di erences, many authorities reserve a diagnostic evaluation or a patient who cannot tolerate an ACE inhibitor or ARB(typically because o hyperkalemia, or a rise in serum creatinine > 25% over baseline), or whose blood pressure cannot be controlled to < 140/90 mm Hg with maximal medical therapy. Some would add patients with recurrent ash pulmonary edema, but the evidence or this is anecdotal. Inpatient management I the patient has a moderate probability o renovascular hypertension and an indication or percutaneous intervention, one o our screening tests is recommended, based on local availability and expertise (Table 244-3). Centers with very experienced Doppler ultrasound laboratories have reported excellent per ormance characteristics and the ability to predict a blood pressure response a ter intervention (renal resistive index < 80 mm Hg) with this noninvasive and relatively inexpensive test. High-resolution CT angiograms are highly sensitive or diagnosis, but they involve radiation exposure and injection o potentially nephrotoxic contrast medium. Magnetic resonance angiograms are quite sensitive and speci c, and avoid exposure to iodinated contrast or radiation. However, they are generally not per ormed (unless dialysis is undertaken immediately a ter the procedure), i the eGFRis less than 60 mL/min/1.73 m 2 because o the risk o irreversible gadolinium-associated nephrogenic brosing dermopathy. Conventional catheter angiography allows or treatment immediately ollowing the discovery o a stenosis, but has the 2003

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TABLE 244-2 Calculation of the Pretest Probability of Renovascular Hypertension

Clinical Characteristic Age (in y) 20-29 30-39 40-49 50-59 60-69 70-79 Female gender ASCVD* Hx HTN ≤ 2 y BMI < 25 kg/m 2 Abdominal bruit Serum creatinine 0.5-0.75 mg/dL 0.75-1.0 mg/dL 1.0-1.2 mg/dL 1.2v1.65 mg/dL 1.7-2.2 mg/dL ≥ 2.3 mg/dL Hypercholesterolemia (> 250 mg/dL, or on treatment)

Never Smoked

Current or Former Smoker

0 1 2 3 4 5 2 1 1 2 3

0 4 8 5 5 6 2 1 1 2 3

0 1 2 3 6 9 1

0 1 2 3 6 9 1

For a given patient, points rom the table are summed; i > 15, the probability is ≥ 70% and angiography is recommended as the initial test; i < 10, the probability is < 15% and screening tests are unlikely to be warranted. * ASCVD, signs, symptoms, or clinical evidence o atherosclerotic cardiovascular disease; BMI < body mass index (weight in kg/[height in cm]2); Hx HTN, history o hypertension. Data rom Krijnen P, van Jaarsveld BC, Steyerberg EW, Manin’t Veld AJ, Schalekamp MA, Habbema JD. A clinical prediction rule or renal artery stenosis. Ann Intern Med. 1998;129:705-711; and Krijnen P, Steyerberg EW, Postma CT, Flobbe K, de Leeuw PW, Hunink MGM. Validation o a prediction rule or renal artery stenosis. J Hypertens. 2005;23:1583-1588.

same risks o contrast and radiation exposure as CT angiogram and is also invasive (Figure 244-3). Although the captopril scintigram is relatively inexpensive, has been validated in large number o patients, and helps predict the results o angioplasty, the American Heart Association no longer recommends its use as a screening test, citing its limited utility in patients with signi cant azotemia, bilateral renal artery stenosis, or renal artery stenosis limited to a single kidney. In the past, angioplasty was o ten delayed until the results o hormonal or hemodynamic measurements were obtained, but this has allen into dis avor, as longer or repeated procedures were usually required. Advances in angiography, stent placement, and protection o distal circulation have improved the success rates o percutaneous renal artery revascularization. This procedure is now the treatment o choice or most types o bromuscular dysplasia, but its role in atherosclerotic disease remains controversial. The Dutch Renal Artery Stenosis Intervention Cooperative (DRASTIC) trial showed no bene t o angioplasty, although a care ul reading o the 12-month data shows signi cantly better blood pressure control in the instrumented group. The Stent or Atherosclerotic Ostial Stenosis o the Renal Artery (STAR) study and the Angioplasty and Stent or Renal Artery Lesions (ASTRAL) study have also shown no signi cant 2004

di erences across randomized arms, suggesting that the results o earlier meta-analyses showing no bene t to the invasive procedure might be correct. The 947-patient, NIH-sponsored, Cardiovascular Outcomes in Renal Atherosclerotic Lesions (CORAL) trial ound a consistently lower systolic blood pressure (by 2.3 mm Hg), and a non-signi cant, 6% reduction in a composite o cardiovascular and renal events a ter angioplasty (compared to medical therapy alone) over 43 months o ollow-up. These results have had a predictably negative impact on prior authorizations or renal angioplasty in most managed care plans in the USA.

■ CUSHING SYNDROME Evaluation Cushing syndrome is caused by prolonged exposure to glucocorticoids. Pituitary adenoma (Cushing disease) causes 75% o endogenous Cushing’s syndrome, about 15% is caused by ectopic ACTH-secreting malignancies, especially small cell lung cancer and carcinoid tumors, and 10% is caused by adrenal hyperplasia, adenomas, and carcinomas. Patients with Cushing syndrome have moon acies with central obesity and peripheral wasting, skin ragility and atrophy, with purplish striae and easy bruising, muscle wasting and proximal myopathy, and dorsocervical at pad (bu alo hump). Other eatures o Cushing syndrome are non-speci c, such as diabetes, diastolic hypertension, hirsutism, irregular menses, and depression. Most patients with signs and symptoms o glucocorticoid excess can be correctly diagnosed with an initial urinary ree cortisol level > 100 µg/d, a morning or evening cortisol level (sometimes now obtained rom saliva, rather than blood), and the classical low-dose and high-dose dexamethasone suppression tests. When these are inconsistent, repetition o the tests or endocrinology consultation is o ten help ul. The ability to assay both corticotropin-releasing hormone and corticotropin ( ormerly known as adrenocorticotropic hormone, or ACTH) has also simpli ed the hormonal diagnosis, but results o ten return a ter hospital discharge. Radiologic studies to localize the tumor to the le t or right side o the pituitary or le t or right adrenal are o ten per ormed be ore the surgeon operates. Inpatient management De nitive management o Cushing syndrome is surgical resection o the responsible pituitary adenoma, ectopic ACTH-producing tumor, or adrenal neoplasm. Medical therapy may be use ul in patients with tumors that cannot be localized, such as some ectopic ACTHproducing lesions, are unresectable, or are producing symptoms severe enough to need urgent treatment prior to surgery. Etomidate and metyrapone reversibly inhibit 11-deoxycortisol ß-hydroxylase, which catalyzes the nal step in cortisol biosynthesis. Ketoconazole inhibits the early stages o steroid synthesis. Mitotane is an adrenolytic agent typically used in the treatment o adrenal carcinoma. Hospitalists involved in the postoperative care o patients with Cushing syndrome should bear in mind that hydrocortisone supplementation is indicated a ter success ul tumor resection, due to suppression o the hypothalamic-pituitary axis. Glucocorticoid replacement may need to be continued or several months and tapered o slowly.

■ PHEOCHROMOCYTOMA Evaluation Pheochromocytoma classically presents with hypertensive episodes (spells), with some combination o palpitations, headaches, sweating, pallor, weakness, nausea, and dyspnea. However, a signi cant minority o patients present with severe hypertension, without paroxysms or spells. The initial step in diagnosis o pheochromocytoma is demonstration o overproduction o catecholamines or their metabolites.

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Figure 244 2 Suggested diagnostic algorithm for most patients with renovascular hypertension. RRI, renal resistance index.

Either plasma- ree metanephrines or 24-hour urinary ractionated metanephrines may be used as a screening test; plasma- ree metanephrines are somewhat more sensitive and logistically easier to obtain. I either is elevated, MRI or CT o the abdomen should be

obtained. I these are negative and pheochromocytoma or paraganglionoma is still suspected, the tumor may be localized with either 131 I-meta-iodobenzylguanidine (MIBG) scan or positron emission tomographic (PET) scan.

TABLE 244-3 Summary of Advantages and Disadvantages of Various Screening Tests for Renovascular Hypertension Screening Test Number o publications (1990-2009) Number o patients Sensitivity (range) Speci icity (range) Advantages

Disadvantages

Doppler Ultrasound 67

Captopril Scintigraphy 71

4640 0.83 (0.17-1.00) 0.84 (0.55-1.00) Noninvasive, inexpensive, may predict BP results a ter revascularization

5068 0.77 (0.09-1.00) 0.78 (0.44-1.00) Noninvasive, not expensive, may predict BP results a ter revascularization Less accurate in renal impairment, bilateral disease, obstructive uropathy

Operator dependent; less use ul in obesity, bowel gas, branch lesions, FMD

Magnetic Resonance Angiogram 71

Computed Tomographic Angiogram 18

3069 0.90 (0.54-1.00) 0.86 (0.21-1.00) No iodinated contrast needed; excellent image quality

1336 0.84 (0.63-1.00) 0.91 (0.56-1.00) Excellent image quality

Expensive, poor images with stents or distal stenoses (eg, FMD), overcalls moderate stenoses; risk o gadolinium-associated nephrogenic ibrosing dermopathy

Expensive, timeconsuming to process and interpret; not widely available; large amount o contrast sometimes needed

BP, blood pressure; FMD, ibromuscular dysplasia. Adapted rom: Elliott WJ. Secondary hypertension: Renovascular hypertension. Chapter 8 in: Black HR, Elliott WJ, eds. Hypertension: ACompanion to Braunwald’s Heart Disease, 2nd ed. Philadelphia, PA: Elsevier, 2013, p. 73.

2005

P A R T V I C l i n i c a l C o n d i t i o n s i n t h e I n p a t i e n t S e t t i n g

Figure 244 3 Abdominal aortogram revealing left renal artery fibromuscular dysplasia (arrows) with a characteristic “string-of-beads” appearance. (Reproduced, with permission, rom Brunicardi FC, Andersen DK, Billiar TR, et al. Schwartz’s Principles of Surgery, 9th ed. New York, NY: McGraw-Hill; 2008. Fig. 23-44.)

Inpatient management Alpha-blockers are used or preoperative blood pressure control, traditionally with oral phenoxybenzamine or intravenous phentolamine when urgent control is required; postural hypotension is a troublesome adverse e ect, and patients should be monitored when ambulating. Beta-blockers may paradoxically worsen blood pressure, and should be given only a ter ull alpha-blockade has been achieved. A laparoscopic approach is becoming more common or solitary adrenal pheochromocytomas. Genetic testing or pheochromocytoma-associated syndromes, such as multiple endocrine neoplasia type 2, is generally recommended.

■ COARCTATION OF THE AORTA Evaluation Although most patients with this disorder are diagnosed and treated as children, many with less severe coarctation remain undetected until adulthood. Clinical clues include di erence in blood pressure o > 15/10 mm Hg between arms, a lower BP in a leg than the ipsilateral arm, or rib notching on chest X-ray (Figure 244-4). Many diagnostic techniques have been employed, but transthoracic echocardiography with suprasternal notch views is quite sensitive and probably the least expensive. Inpatient management Catheter-based interventions have been success ul in many adults, especially in patients with discrete, short-segment coarctation, but most remain hypertensive a ter relie o the coarctation. Compared to surgery, balloon angioplasty and stenting has lower acute complication rates, but higher rates o restenosis. 2006

Figure 244 4 Rib notching (arrows) caused by dilation of intercostal collaterals in a patient with coarctation of the aorta. (Reproduced, with permission, rom Fuster V, O’Rourke RA, Walsh RA, et al. Hurst’s the Heart, 12th ed. New York, NY: McGraw-Hill; 2008. Fig. 15-1B.)

DISCHARGE CHECKLIST

■ KNOWN OR SUSPECTED SLEEP APNEA • Has a sleep study been per ormed or arranged in an outpatient

sleep clinic? • Do patients with known sleep apnea have access to a CPAP machine with a properly tted mask?

■ CHRONIC KIDNEY DISEASE • Is outpatient ollow-up arranged to recheck the patient’s blood

pressure in the next 1 to 2 weeks (target < 140/90 mm Hg, or < 130/80 mm Hg as suggested by the 2012 KDIGO guideline)? • Has ollow-up been arranged to recheck urinary albumin:creatinine ratio, serum creatinine, and estimated glomerular ltration rate in 4 to 6 weeks? • Is an ACE-inhibitor or ARB part o the patient’s antihypertensive drug regimen (i not contraindicated)?

■ HYPERALDOSTERONISM • Has ollow-up been arranged or determination o of ce blood

pressure and serum potassium, and to ollow-up on the results o the plasma aldosterone/plasma renin ratio, i this is still pending at the time o hospital discharge? • For patients with glucocorticoid-remediable hyperaldosteronism, has ollow-up been arranged or monitoring o glucose, cholesterol, and bone density (as higher than physiologic doses o corticosteroids are o ten needed, leading to iatrogenic Cushing syndrome)?

■ RENAL ARTERY STENOSIS • Has of ce ollow-up been arranged or adjustment o blood pres-

sure medications and monitoring o serum potassium, lipids, and

■ COARCTATION OF THE AORTA • Has outpatient ollow-up been arranged to check of ce blood

pressure, serum potassium, and creatinine in 2 to 4 weeks, with tapering o antihypertensive medication (typically a beta-blocker), as easible?

SUGGESTED READINGS Calhoun DA, Jones D, Textor S, et al. Resistant hypertension: diagnosis, evaluation, and treatment. A scienti c statement rom the American Heart Association. Hypertension. 2008;51:1403-1419. Cooper CJ, Murphy TP, Cutlip DE, et al. Stenting and medical therapy or atherosclerotic renal-artery stenosis. N Engl J Med. 2014;370:13-22.

Rossi GP, Auchus RJ, Brown M, et al. An expert consensus statement on use o adrenal vein sampling or the subtyping o primary aldosteronism. Hypertension. 2014;63:151-160.

C H A P T E R 2 4 4 S e c o n d a r y H y p e r

Prague JK, May S, Whitelaw BC. Cushing’s syndrome. BMJ. 2013;346: 945.

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serum glucose, potassium, and creatinine, usually 2 to 4 weeks a ter discharge, with tapering o alpha-blockade as easible? • Has repeat testing been arranged or catecholamine overproduction (usually done 6-8 weeks a ter discharge, using whichever modality demonstrated the abnormality be ore the operation)? • Has ollow-up been arranged to review the results o genetic screening or amilial syndromes that include pheochromocytoma, and to pursue urther testing or rst-degree relatives, i indicated?

Lenders JWM, Duh Q-Y, Eisenho er G, et al. Pheochromocytoma and paraganglioma: an Endocine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2014;99:1915-1942.

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• Has ollow-up been arranged to obtain of ce blood pressure,

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■ PHEOCHROMOCYTOMA

Hu X, Fan J, Chen S, Yin Y, Zrenner B. The role o continuous positive airway pressure in blood pressure control or patients with obstructive sleep apnea and hypertension: a meta-analysis o randomized controlled trials. J Clin Hypertens (Greenwich). 2015;17:215-222.

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serum glucose, potassium, and creatinine, usually 2 to 4 weeks a ter discharge, along with results o any pending diagnostic tests?

i

• Has ollow-up been arranged to check of ce blood pressure,

Herrmann SM, Saad A, Textor SC. Management o atherosclerotic renovascular disease a ter Cardiovascular Outcomes in Renal Atherosclerotic Lesions (CORAL). Nephrol Dial Transplant. 2015;30:366-375.

o

■ CUSHING SYNDROME

Funder JW, Carey RM, Fardella C, et al. Case detection, diagnosis, and treatment o patients with primary aldosteronism: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2008;93:3266-3281.

n

creatinine? This is needed on a monthly basis or several months ollowing revascularization. Postprocedure ollow-up is critical or patients with renovascular hypertension, as the diagnosis is only made retrospectively, by showing lower of ce blood pressure 6 to 12 weeks a ter opening the stenosis.

Stevens PE, Levin A. For the Chronic Kidney Disease Guideline Development Work Group Members. Evaluation and management o chronic kidney disease: synopsis o the Kidney Disease: improving Global Outcomes 2012 clinical practice guideline. Ann Intern Med. 2013;158:825-830. Vongpatanasin W. Resistant hypertension: a review o diagnosis and management. JAMA. 2014;311:2216-2224. Warnes CA, Williams RG, Bashore TM, et al. ACC/AHA 2008 guidelines or the management o adults with congenital heart disease. Circulation. 2008;118:e715-e811. Weber BR, Dieter RS. Renal artery stenosis: epidemiology and treatment. Int J Nephrol Renovasc Dis. 2014;7:169-181. White WB, Turner JR, Sica DA, et al. Detection, evaluation, and treatment o severe and resistant hypertension: proceedings rom an American Society o Hypertension interactive orum held in Bethesda, MD, USA, October 10, 2013. J Am Soc Hypertens. 2014;8:743-757.

2007

245

CHAP TER

Chronic Kidney Disease and Dialysis Ursula C. Brewster, MD Jef rey Turner, MD

Key Clinical Questions 1

How are the stages o chronic kidney disease de ined?

2

What are the di erent dialysis modalities, and how do patients choose one over another?

3

What is the di erence between an arteriovenous istula and an arteriovenous gra t? What are their associated complications?

4

When is it appropriate to initiate dialysis?

5

How are hemodialysis and peritoneal dialysis per ormed? What are their common complications?

6

What complications are common in hospitalized patients with chronic kidney disease?

INTRODUCTION Over 26 million Americans, or approximately one in nine adults, have chronic kidney disease (CKD). These patients require special attention rom hospitalists because o the high incidence o acute kidney injury (AKI) and other complications during hospitalization. These patients are at risk o AKI not only rom known nephrotoxins, such as contrast agents and nonsteroidal anti-in ammatory drugs (NSAIDs), but also rom other commonly prescribed agents. Other major issues in the hospital care o these patients include preservation o venous access, electrolyte and acid-base correction, and anemia management. As many o these patients advance to end-stage renal disease (ESRD) requiring dialysis, hospitalists should have a basic understanding o the principles o renal replacement therapy (RRT). CHRONIC KIDNEY DISEASE The National Kidney Foundation has de ned a staging system or CKD (Table 245-1) based on glomerular ltration rate (GFR) as the best marker o kidney unction. CKD is de ned as an absolute GFR less than 60 cc/min, or structural or unctional kidney abnormalities such as hematuria, proteinuria, or abnormal renal imaging in association with a preserved GFR (> 90cc/min). Serum creatinine concentration (sCr) is a poor marker o kidney unction, as normal values vary signi cantly with age, gender, and muscle mass. It is especially inadequate in the setting o AKI. In the early phases o acute kidney injury, the sCr may be alsely reassuring, as it may begin to rise well a ter the initial insult. As GFR is not readily measured, mathematical ormulae are used to estimate it. The Cockcro t-Gault and the Modi cation o Diet in Renal Disease (MDRD) ormulas are most commonly used. The newer Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation is also being used in some clinical laboratories (Table 245-2). The Cockcro t-Gault ormula is simple, but o ten overestimates kidney unction. The MDRD is a more arduous calculation, but is more accurate in patients with advanced CKD. The CKD-EPI equation is superior to the others in that it allows or accurate GFR estimations in patients with normal or minimally impaired kidney unction. These ormulas are only use ul when sCr is in a steady state. When the sCr is rapidly changing, as in acute kidney injury, they are completely inaccurate and should not be used. In that case, a 24-hour urine collection or creatinine clearance (CrCl) is a better indicator o kidney unction. A 24-hour urine collection is recommended whenever renally excreted drugs possessing signi cant toxicity need to be administered. TREATMENT OF CHRONIC KIDNEY DISEASE Chronic kidney disease, no matter the etiology, is almost always a progressive, irreversible process. Treatment strategies ocus on slowing the decline in kidney unction, as there are no currently available treatments proven to reverse CKD. The interventions with the best evidence or slowing disease progression are control o hypertension and the use o angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers in patients with proteinuria. Additional evidence suggests that it may be bene cial to correct metabolic acidosis, hyperphosphatemia, and vitamin D de ciency. It is unclear whether lipid lowering and strict glucose control in diabetes a ects CKD progression, but these strategies are employed in most patients. Despite optimal medical care, patients with advanced CKD o ten

2008

PREPARATION OF PATIENTS FOR DIALYSIS

■ DIET EDUCATION Patients with advanced CKD need instruction about the importance o dietary adherence. Diets or stage 5 CKD are restricted in sodium, potassium, and phosphorus. In the past, CKD patients were told to dramatically limit protein intake, as it was thought that this would slow progression o proteinuric kidney disease. Most experts now agree that a modest protein restriction (0.7 g/kg/d) is likely sa e, but more restricted diets pose too great a risk o malnutrition. Salt restriction in patients with CKD cannot be overemphasized. Potassium restriction is also important in advanced disease.

TABLE 245-2 Estimation Formulas o Glomerular Filtration Rate Cockcro t-Gault equation: (140 − age) × (IBW) SCr × 72 MDRD equation: 170 × (SCr)–0.999 × (Age)–0.176 × (0.762 i emale) × (1.80 i black) × (BUN)–0.170 × (albumin)0.318 CKD-EPI equation: GFR = 141 × min(SCr/κ,1)α × max(SCr/κ,1)-1.209 × 0.993Age × 1.018 (i emale) × 1.159 (i black) κ = 0.7 i emale κ = 0.9 i male α = -0.329 i emale α = -0.411 i male min = the minimum o SCr/κ or 1 max = the maximum o SCr/κ or 1 BUN, blood urea nitrogen; IBW, ideal body weight; MDRD, modi ication o diet in renal disease; SCr, serum creatinine; CKD-EPI, chronic kidney disease epidemiology collaboration; GFR, glomerular iltration rate. Units: Age in years; Albumin in g/dL; BUN in mg/dL; IBW in kg; SCr in mg/dL.

C H A P T E R 2 4 5 C h r o n i c K i d n e y D i s e a s e d

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Modalities o dialysis that hospitalists should be amiliar with include peritoneal dialysis (PD), traditional in-center hemodialysis (HD), home HD, and nocturnal HD (Table 245-3). These modalities are discussed in detail below. The choice should be based on dialysis access options, patient li estyle, and patient support network.

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progress to ESRD. When easible, ESRD is best treated with transplantation. When donors are available, this is done preemptively, and dialysis is avoided. I dialysis seems unavoidable, preparation and discussion should start at least 1 year in advance, involving the patient, primary care physician, amily, nephrologist, and other caregivers. However, some patients require acute dialysis in the hospital, with quick education by hospitalists and nephrology teams.

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Description Patient goes to a dialysis clinic or treatment, typically three times a week Patient or partner needles the patient’s access, and runs his or her treatments on a compact hemodialysis machine, either daily or a scheduled number o treatments per week Nocturnal Patient goes to a dialysis clinic at night, and hemodialysis undergoes longer hemodialysis treatments by skilled nurses overnight during sleep Continuous Patient does 4-6 manual exchanges o ambulatory dialysate into the abdomen over the course peritoneal dialysis o a 24-h period Automated Peritoneal dialysis is done via an automated peritoneal dialysis machine that cycles luid in and out o the abdomen over a set period o time (usually 8-10 h), o ten during sleep

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Description At increased risk Kidney damage with normal or increased GFR Kidney damage with mild decrease in GFR Moderate Severe decrease in GFR Kidney ailure

Modality In-center hemodialysis Home hemodialysis

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TABLE 245-3 Dialysis Modalities

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TABLE 245-1 Chronic Kidney Disease Staging System

■ HEMODIALYSIS ACCESS PLANNING When the need or HD is urgent, dual-lumen dialysis catheters can be placed at the bedside or radiology suite by nephrologists, surgeons, or interventional radiologists. These may be used immediately a ter con rmation o placement by radiography. The internal jugular and emoral veins are pre erred sites. Catheters should not be placed in the subclavian vein, because central venous stenosis may develop, precluding the later use o the ipsilateral arm or surgically created stulae and gra ts. Catheters may be untunneled, or tunneled with subcutaneous cu s. Tunneling the catheter subcutaneously prior to vein entry decreases the likelihood o skin bacteria reaching the bloodstream and causing in ection, and allows these catheters to remain in place or longer periods o time. Catheters are not pre erred or long-term vascular access. They have high rates o mal unction and in ection (approximately 2-4 episodes per 1000 patient days) and are associated with increased patient mortality, compared with stulae or gra ts. Ideally, access or HD is established well in advance o the need to start dialysis, as an arteriovenous stula (AVF) may need months to mature be ore it is viable. Patients with CKD should be re erred to an experienced access surgeon when their estimated GFR is 20 mL/min/1.73 m 2, or when they are expected to require dialysis in the next 3 to 6 months. Long-term vascular access or HD requires identi cation and preservation o suitable veins over time. Fistulae require veins greater than 0.3 cm in diameter on ultrasound mapping. The importance of vein preservation cannot be overemphasized. Many CKD patients will require HD access and should have their veins protected, particularly while hospitalized. To this end, one upper extremity (usually the nondominant arm) should be spared rom blood draws, sphygmomanometers, and intravenous catheters (including peripherally inserted central catheter [PICC] lines). Scarring o veins occurs rapidly, o ten making uture access creation impossible. Arteriovenous stulae are pre erred over synthetic arteriovenous gra ts because o their longer li espan and lower in ection rate. An AVF is made by surgically anastomosing a native artery to a native 2009

Dia lys a te

Blood inflow

Blood outflow

Severe metabolic abnormalities (hyperkalemia, hypercalcemia) Severe acidosis not responsive to bicarbonate therapy Intoxications and overdoses (ie, methanol, ethylene glycol, lithium, theophylline, salicylates, met ormin) Severe volume overload not responsive to diuretics Uremia in the setting o chronic renal ailure

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TABLE 245-4 Acute Indications or Dialysis

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Figure 245 1 Arteriovenous fistula showing the direct anastomosis between artery and vein in the upper extremity.

vein, usually in the orearm or upper arm (Figure 245-1). Over time, the vein will “arterialize,” so it can withstand thrice-weekly cannulation. Fistula maturation usually requires 6 to 12 weeks. Surgical or percutaneous interventions may be required when maturation is delayed. A success ul stula can last over a decade with low thrombosis and in ection rates.

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PRACTICE POINT

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Because many CKD patients will require HD access, clinicians should preserve their veins during hospitalization. This means ensuring that one upper extremity (usually the non-dominant arm) is spared rom blood draws, sphygmomanometers, and intravenous catheters (including PICC lines). Scarring o veins occurs rapidly, o ten making uture access creation impossible.

I a suitable vein or creation o an AVF is unavailable, an arteriovenous gra t (AVG) made o polytetra uoroethylene (PTFE) or other synthetic material may be interposed between native vessels as an alternative (Figure 245-2). An AVG can be used or HD 2 to 4 weeks a ter placement. Un ortunately, synthetic PTFE gra ts are not as durable as an AVF. On average, gra ts thrombose more o ten than stulae and have lower patency rates. Additionally, because these gra ts are made o synthetic material, in ection usually requires surgical excision and abandoning the access. INITIATION OF DIALYSIS In some patients, CKD slowly progresses and dialysis can be initiated in a predictable ashion. For others, AKI necessitates urgent initiation o treatment.

Radial-c e phalic AVF

There are several li e-threatening scenarios that warrant urgent nephrology consultation and initiation o dialysis, with immediate placement o a double-lumen dialysis catheter or access (Table 245-4). These catheters are most o ten untunneled. In addition, these temporary dialysis catheters are pre erred in patients with bacteremias or other endovascular in ections. I there are no in ectious issues, a tunneled dual-lumen catheter can be placed or dialysis, with lower long-term in ection risks.

■ CHRONIC INITIATION Dialysis in progressive CKD is undertaken to avoid complications o advanced uremia. Current guidelines (and Medicare reimbursement) recommend the initiation o dialysis when creatinine clearance drops below 10 mL/min. Diabetic patients seem more susceptible to the side e ects o uremia, and may require dialysis when the creatinine clearance alls below 15 mL/min. In patients with CKD, physiologic derangements begin well be ore the need or dialysis. Spontaneous decreases in protein intake, anemia, and altered calcium, phosphorus, and PTH homeostasis may begin when creatinine clearance is as high as 30 to 40 mL/min. Early nephrology re erral helps manage these early complications o CKD and allows or a smooth transition to dialysis. Patients who have been actively managed by a nephrologist well be ore dialysis have better outcomes than patients seen later in the disease process. Uremia results rom high levels o nitrogenous wastes and other toxins in the blood. Gastrointestinal symptoms such as nausea, vomiting, and anorexia are prominent. Central nervous system (CNS) symptoms include atigue, con usion, tremors, seizure, and coma. Abnormal platelet unction, with a prolonged bleeding time and high risk o hemorrhage, is also common. Classic physical exam ndings, such as a pericardial riction rub, asterixis, and wrist or oot drop, may signal the need or more urgent dialysis. HEMODIALYSIS Hemodialysis (HD) is based on the di usion o solutes across a semipermeable membrane down a concentration gradient (Table 245-5).

TABLE 245-5 De initions Dialysis

Arte ry

Ultra iltration Hemo iltration

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Figure 245 2 Arteriovenous graft showing artificial graft material (black) placed as a conduit between artery and vein in the upper extremity. 2010

Hemodia iltration

The clearance o small molecules and toxins using di usion across a native (peritoneal) or synthetic semipermeable membrane Fluid removal across a semipermeable membrane during dialysis by convection Continuous dialysis therapy in which large amounts o luid are removed by convection rom blood, with concurrent rein usion o an electrolytic solution The combination o hemodialysis and hemo iltration

■ VASCULAR ACCESS COMPLICATIONS Bleeding Hemorrhage rom HD access can be caused by needle laceration or intrinsic access problems. Out ow stenosis can increase pressure TABLE 245-6 Common Components o Dialysate Bath on Hemodialysis Component Sodium (mEq/L) Potassium (mEq/L) Calcium (mEq /L) Bicarbonate (mEq/L) Glucose (mg/dL)

Concentration Range Typical 135-155 140 0-4 2 0-3.5 2.5 25-40 35 100-200 200

C H A P T E R 2 4 5 C h r o n i c K i d n e y D i s e a s e a n d D i a

Clot ormation is the most common cause o arteriovenous access loss. Sluggish blood ow rom acquired venous stenosis is the usual cause. AVGs are especially prone to thrombose, as they o ten develop neointimal hyperplasia and venous stenosis at anastomosis sites. Access salvage in the setting o thrombosis is most success ul early, in the rst 24 to 48 hours. Treatments or established thrombosis include thrombolytic agents, percutaneous or surgical thrombectomy, and mechanical dissolution. Venous stenosis, i present, should be angioplastied at the time o thrombolysis to reduce the likelihood o recurrence. Fistulae are less likely to become stenotic, but the arterial in ow and venous out ow must be assessed at the time o the declotting procedure.

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Heparinized blood is pumped through a synthetic dialyzer at 300 to 500 cc/min, while individualized dialysate is run countercurrently at 500 to 800 cc/min (Figure 245-3). Solutes and water di use across the dialyzer, which is made o a semipermeable membrane that separates blood and dialysate. Dialysis replenishes bicarbonate, removes nitrogenous wastes, and balances electrolytes and divalent ions. The dialysis circuit consists o a heparin pump, a blood pump, an air leak detector, and arterial and venous pressure monitors. The dialysis machine alerts sta i it detects blood or air leaks, blood clots, or variability in patient blood pressure and heart rate. Because 30 to 40 gallons o water are used during each dialysis treatment, water puri cation systems are used to remove bacteria, endotoxin, trace metals, and other contaminants. The major constituents o the dialysis solution are listed in Table 245-6. These are adjusted in the dialysis prescription, depending on the patient’s serum potassium, serum calcium, and acid-base balance. The length o the dialysis session is based on measurement o dialysis adequacy to ensure the patient is achieving adequate clearance. Solute clearance, determined by the reduction o urea per treatment, is measured regularly by calculating Kt/V, where K equals the clearance coe cient, t equals duration/time o each dialysis treatment, and V equals volume o distribution o urea. This is regularly calculated in every HD patient, with a targeted goal o 1.4 or greater. I a patient’s value alls short, dialysis time is increased to improve clearance. Patients with de cient solute removal are at risk o uremic symptoms, including poor appetite, atigue, pruritus, and pericarditis. In general, patients require between 3 and 4 hours o dialysis per treatment or adequate clearance. Larger patients need more time. Dialysis adequacy may be jeopardized by inadequate blood ow through a vascular access, small dialyzer sur ace area, and missed or early termination o dialysis sessions by patients. Be ore HD can be initiated, vascular access that will provide adequate blood ow (300-500 cc/min) must be in place.

Thrombosis

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Figure 245 3 Hemodialysis cartridge.

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Arte ry

within the access, and predispose patients to prolonged bleeding a ter needle removal. Needles repeatedly placed at the same site in the access can weaken it, leading to an aneurysm in a stula or a pseudoaneurysm in a gra t. These de ects may rupture, leading to exsanguination. There ore, needle sites must be rotated within the access. Bleeding also occurs in the setting o in ection, particularly in AVGs. Spontaneous bleeding rom an AVG requires surgical repair or excision to prevent recurrent bleeding. I a stula is lacerated and bleeds, it can sometimes be salvaged with rest, unlike an AVG. Repair will be necessary i an aneurysm is present. Immediate surgical consultation is mandatory in any case o access site bleeding.

Infection

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Fo re arm lo o p AVG

Dialysis catheters have high rates o in ection and bacteremia. Empiric antibiotic therapy should include vancomycin and a second intravenous antibiotic active against gram-negative bacilli. However, antibiotics alone are not e ective at curing catheter in ections. This is particularly true o dialysis catheters in ected with Staphylococcus aureus, Candida species, and Pseudomonas. These should always be removed, and a nontunneled catheter should be inserted at another site. (I no other viable access sites exist, the catheter should be exchanged over a guidewire as a last resort.) Patients with Staphylococcus aureus bacteremia are at high risk o metastatic in ection, and they should be monitored or the development o complications such as endocarditis, epidural abscess, osteomyelitis, septic arthritis, endophthalmitis, and meningitis. Patients with catheter in ection with less virulent organisms, such as coagulase-negative staphylococci, can be treated with intravenous antibiotics initially. I symptoms do not resolve in 48 to 72 hours, the catheter should be removed. I the patient improves clinically, the in ected catheter can be exchanged over a guidewire, and intravenous antibiotics can be continued. Alternatively, in those patients who improve rapidly with antibiotics, the catheter can be le t in place and intravenous antibiotics can be continued, together with adjunctive antibiotic lock therapy (antibiotic solutions le t in the catheter lumen a ter dialysis). Arteriovenous gra t in ections require total excision o the gra t and intravenous antibiotic therapy. In ections o arteriovenous stulae are less common, as native vessels are more resistant to in ection. In ected stulae may o ten be cured with intravenous antibiotics alone. Duration o intravenous therapy or catheter in ection is at least 2 weeks. Surveillance blood cultures should be obtained 1 week a ter stopping antibiotics i the in ected catheter has been retained. I these are still positive, the catheter should be removed. Patients with persistent bacteremia and ungemia a ter catheter removal should receive at least 4 to 6 weeks o antibiotic therapy. Arterial steal syndrome Gra ts and stulae divert arterial blood into the venous system and away rom distal tissues, resulting in digital ischemia. Symptoms include coldness and cramping o the hand, numbness, tingling, pain, 2011

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or overt ischemia with discoloration. Patients with new gra ts and stulae should be care ully monitored or these symptoms, particularly in those with peripheral vascular disease. This syndrome can also present late, as a stula matures, enlarges, and steals larger volumes o blood. In extremely large stulae, high-output cardiac ailure can occur, but this is rare.

■ PROCEDURAL COMPLICATIONS OF HEMODIALYSIS Hypotension is the most common adverse event associated with HD, occurring during 25% to 55% o treatments. Dialysis removes urea rom the extracellular space, creating an osmolar gradient rom the extracellular to the intracellular space. Fluid shi ts to the intracellular space lead to extracellular volume depletion. In addition, when patients are noncompliant with uid restriction, removal o large volumes is sometimes required to reach a target dry weight in a single 3- to 4-hour dialysis session. Rapid removal o volume o ten results in hypotension, as uid does not have time to re-equilibrate rom the interstitial to the intravascular space. Boluses o saline, albumin, or mannitol are given to transiently increase blood pressure. Strategies to prevent episodic hypotension include reduced dialysate temperature, high sodium dialysate, and medications such as the alpha-agonist midodrine. The symptoms o dialysis disequilibrium include headache, nausea, con usion, restlessness, blurred vision, asterixis, and seizures. It is most common in chronically uremic patients beginning dialysis. The osmolar gradient resulting rom rapid reduction in serum urea leads to water entry into neurons and cerebral edema. Dialysis disequilibrium is prevented by conducting the rst several dialysis treatments at low blood ows and short duration. Cardiac arrhythmias may occur in the setting o dialysis and are related to rapid uctuations in potassium, calcium, and magnesium. ESRD patients with underlying cardiac disease are at higher risk. Quality of life complications associated with HD include nausea, cramping, headache, chest pain, and itching. Individual patients may be plagued with these symptoms to the point o intolerance. PERITONEAL DIALYSIS In peritoneal dialysis (PD), the patient’s peritoneum is used as a semipermeable membrane through which di usion, convection, and ultra ltration occur. Many patients pre er PD over HD because o the greater exibility and control that PD allows. Unlike HD, residual renal unction is o ten necessary or adequate solute clearance, so e orts should be made to preserve it in these patients, even i it is minimal. Patients with prior major abdominal surgery may have adhesions that could limit the ow o dialysate, and there ore may not be candidates or PD. Laparoscopic PD catheter placement allows assessment o the suitability o the peritoneum in these patients. As PD is usually a home modality, an evaluation o social supports is essential. Morbidly obese patients or brittle diabetics are less than optimal candidates or PD because o high glucose exposure. However, many well-controlled diabetics do well on PD with aggressive adjustment o insulin regimens. The basic continuous ambulatory peritoneal dialysis (CAPD) system consists o a bag o dialysis solution, a trans er set that serves as a conduit or uid, and an indwelling silastic catheter. Dialysis solutions or PD contain physiologic concentrations o sodium, magnesium, and calcium, with lactate usually added as a bu er. During PD there is an exchange o solutes and uid between the peritoneal capillary blood supply and the dialysis solution; the blood vessel wall, interstitium, and peritoneal mesothelium compose the semipermeable membrane. A volume o uid, typically between 2 and 2.5 L, is in used through the catheter into the peritoneal cavity and allowed to dwell or a prescribed number o hours. The volume o uid varies with patient com ort and body habitus. The number

2012

o hours the uid is allowed to dwell depends on the innate characteristics o the patient’s peritoneal membrane. Patients are generally categorized as either rapid or slow transporters o solutes and uid. Solutes trans er across the peritoneal membrane, equilibrate with the in used dialysate, and are subsequently drained out o the peritoneal cavity. Dextrose is used as the primary osmotic agent, and standard solutions o 1.5%, 2.5%, or 4.25% are used to acilitate movement o uid into the peritoneal cavity and achieve ultra ltration. Higher dextrose–containing dialysate solutions (4.25%) generate higher osmotic gradients and remove greater volumes o ultra ltrate. However, high-dextrose in usions increase the production o advanced glycosylation end products (AGEs), leading to oxidation and peritoneal membrane damage. This may lead to eventual ailure o the peritoneal membrane and inability to adequately trans er solutes, necessitating a switch to HD. In diabetic patients, higher dextrose–containing solutions will increase serum glucose concentrations and worsen glycemic control. In patients with acute volume overload, large ultra ltration volumes can be achieved with 4.25% dextrose solutions or short dwells (< 1 hour) repeatedly, until the patient’s symptoms improve. Automated PD is an alternative to conventional CAPD. In contrast to manual in usion and drainage o PD solutions, a machine per orms the exchanges. The PD cycler consists o a scale and a dialysate warmer, and in uses, dwells, and drains peritoneal uid. Patients usually undergo automated PD while asleep, allowing greater mobility during the day. The length o time each exchange dwells in the peritoneal cavity is o ten shorter than with CAPD, but the total volume o uid in used is o ten much greater. Children are usually treated with PD because the large extracorporeal blood volume required by the HD tubing and dialyzers can be hemodynamically prohibitive. Patients with severe cardiovascular disabilities also tend to tolerate the gentler daily ultra ltration o PD better than intermittent HD.

■ PERITONEAL DIALYSIS ACCESS A silastic (Tenckho ) catheter is inserted into the peritoneal cavity by a quali ed surgeon, interventional radiologist, or nephrologist, and tunneled beneath the skin to exit on the anterior abdominal wall. A ter placement, it should be immediately ushed with low volumes o dialysate and then capped o . Two weeks are required or wound healing and anchoring o the catheter in the subcutaneous tissue. It may sometimes be used cautiously be ore this 2-week time rame with low uid volumes and maintenance o the supine position, to prevent increased intraabdominal pressure and peritoneal leaks. Patients are care ully trained in how to access the catheter in a sterile ashion. Both patient and provider should be masked, and sterile technique is mandatory. Peritoneal uid samples or laboratory analysis should only be obtained with proper technique by trained providers. Catheters may develop cracks over time; these can o ten be repaired by trained PD sta .

■ PERITONEAL DIALYSIS COMPLICATIONS Peritonitis is the most serious complication o PD. Patients develop abdominal pain and have cloudy dialysate ef uent. Dialysate sampling will demonstrate more than 100 white blood cells, with over 50% polymorphonuclear cells. On average, peritonitis occurs once every 15 to 20 months (a much lower rate than HD catheter in ections). The most common organisms are gram-positive bacteria. Growth o multiple organisms, including gram-negative bacteria, should prompt an evaluation or an intestinal or intra-abdominal source. Nearly 80% o episodes may be managed at home, with the addition o antibiotics to the dialysate. Patients receiving antibiotics should also receive ungal prophylaxis (oral nystatin or uconazole)

COMMON PROBLEMS IN HOSPITALIZED CKD PATIENTS

■ GASTROINTESTINAL BLEEDING ESRD patients, regardless o dialysis modality, are at increased risk o gastrointestinal bleeding rom acquired platelet dys unction and may also be receiving medications such as aspirin and heparin that increase bleeding risk. Dialysis patients are also prone to bleeding rom angiodysplasia, or unclear reasons. Azotemic patients with severe bleeding should be dialyzed. Subcutaneous or intravenous desmopressin, at dosages o 0.3 µg/kg body weight, may be therapeutic in uremic bleeding by releasing von Willebrand actor rom storage sites. There is also evidence to support the use o conjugated estrogens or cryoprecipitate in uremic bleeding. The decision to trans use a CKD patient who is a transplant candidate should be care ully considered, as trans usion is o ten associated with antibody ormation, perhaps hindering the matching o a uture kidney allogra t.

■ HYPERTENSION Hypertension is common in CKD and ESRD patients. Most o these patients should be on renin-angiotensin-aldosterone system inhibitors, such as angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARB), as these improve cardiovascular outcomes and survival and preserve residual renal unction. In hospitalized patients, these medications are problematic because they may increase the risk o AKI and hyperkalemia. They should certainly be stopped in the setting o AKI and in CKD patients undergoing intravenous contrast exposure. When these medications are held in the setting o AKI, practitioners should be sure to restart them once the sCr approaches baseline, to allow or the long-term bene ts o these drugs.

C H A P T E R 2 4 5 C h r o n i c K i d n e y D i s e a s e a n d D i a l

Phosphorus clearance alls with declining GFR, and hyperphosphatemia is common in CKD. It may cause hypocalcemia and tetany in the short term, and renal osteodystrophy and cardiovascular disease in the long term. Serum phosphorus levels should be controlled by dietary restriction as well as oral phosphorus binders (both calcium and noncalcium based) at mealtimes. Calcium-based binders (calcium carbonate or calcium acetate) are less expensive than non– calcium-based binders (sevelamer or lanthanum). In larger doses, they promote positive calcium balance, which appears to contribute to cardiovascular calci cation. Aluminum-based phosphorus binders should be avoided because o their association with dementia and adynamic bone disease in renal ailure. Medications that can worsen phosphorus control, such as phosphorus-containing bowel preparations, should be avoided in hospitalized CKD patients. These have been associated with acute kidney injury rom phosphate overload and should certainly be avoided in patients with stages 3 to 5 CKD.

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■ PHOSPHORUS CONTROL

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For critically ill patients who are hemodynamically unstable, continuous renal replacement therapy (CRRT) is o ten employed. Several modalities exist, including continuous venovenous hemoltration (CVVH), continuous venovenous hemodialysis (CVVHD), continuous venovenous hemodia ltration (CVVHDF), sustained low-e ciency dialysis (SLED), and extended daily dialysis (EDD). They all require a double-lumen catheter, a blood pump with sa ety devices similar to conventional HD, and a dialysis lter. All orms o CRRT must be done in an intensive care unit setting with properly trained sta . CRRT allows or very slow uid removal, resulting in excellent hemodynamic tolerance, even in patients with shock or severe uid overload. In addition, because the therapy is continuous, uid removal and correction o metabolic abnormalities can be modi ed at any time, allowing or rapid adjustment in critically ill patients. CRRT can also compensate or the large uid volumes required or parenteral nutrition. The data on CRRT bene t over conventional HD is not conclusive, but it continues to be employed in critically ill patients who may not tolerate conventional HD, and in those with ulminant hepatic ailure who are at risk or cerebral edema.

Patients with CKD and ESRD su er rom a complex spectrum o bone diseases. Osteomalacia may be seen with isolated vitamin D de ciency. Hyperphosphatemia, hypocalcemia, skeletal resistance to parathyroid hormone (PTH), and impaired renal production o 1, 25-dihydroxyvitamin D may lead to high-turnover bone disease and osteitis brosa cystica. Parathyroid gland hyperplasia may develop and may be di cult to reverse. Patients with secondary hyperparathyroidism may develop bone pain, muscle weakness, and erythropoietin-resistant anemia. Medical treatment to prevent hyperparathyroidism includes oral calcium, active vitamin D preparations, and calcimimetic drugs such as cinacalcet. Parathyroidectomy is still sometimes required. However, i PTH is oversuppressed by medical or surgical therapy, adynamic bone disease may develop. Management o serum phosphorus concentration is critical to the regulation o PTH.

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CONTINUOUS RENAL REPLACEMENT THERAPY

■ BONE DISEASE

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to avoid ungal overgrowth and peritonitis. Fungal peritonitis is devastating, and requires the removal o the peritoneal catheter and either temporary or permanent conversion to HD. Other complications o PD include malnutrition rom loss o albumin and amino acids into the dialysate. Diabetics may struggle with weight gain and hyperglycemia rom dextrose in the dialysate solution. A ter years o PD and the requent use o high-dextrose solutions, the peritoneal membrane may develop scarring and adhesions, which limit solute clearance and ultra ltration. In these cases, it is o ten necessary to switch to HD.

■ USE OF CONTRAST AGENTS Iodinated radiocontrast causes contrast nephropathy, particularly in patients with stages 3 to 5 CKD and diabetes mellitus. It should generally be avoided in these patients, and even patients with ESRD on dialysis, as they bene t rom preservation o even minimal residual renal unction. When use o radiocontrast agents is essential in CKD or ESRD, prophylaxis with intravenous uids (NaCl or NaHCO3) and N-acetylcysteine should be used. Using low or iso-osmolar radiocontrast and limiting contrast volume may also be help ul. Current data do not suggest HD prevents contrast nephropathy. Avoid gadolinium contrast in patients with CKD stages 4 and 5 (GFR < 30 cc/min) because o its devastating association with nephrogenic systemic brosis.

■ ACID-BASE DISORDERS Chronic metabolic acidosis is common in advanced CKD, as the kidney cannot excrete the daily ingested acid load. CKD may be complicated by type 4 renal tubular acidosis, urther worsening acid-base balance. CKD patients are less able to handle an acute acid load, as might occur with lactic acidosis, and may develop severe metabolic acidosis quickly. Oral NaHCO3 and urosemide may be therapeutically e ective, but dialysis may be required in severe cases.

■ MYOCARDIAL INFARCTION Patients with CKD are at higher risk o cardiovascular events, including acute coronary syndrome (ACS). Serum troponin levels (troponin T and I) can be mildly elevated in CKD and ESRD patients. A single 2013

P A R T V I C l i n i c a l C o n d i t i o n s i n t h e I n p a t i e n t S e t t i n g

troponin is not help ul or diagnosing ACS in renal insu ciency, but rising troponins over time suggest acute cardiac injury. Therapy or ACS remains the same as in the general population.

■ ANEMIA MANAGEMENT

In one sample o patients with CKD admitted to community hospitals, adverse drug events (ADEs) related to improper dosing or renal unction occurred in over 50%, with hal o these being classi ed as serious. Commonly misdosed drugs included antibiotics, acetaminophen, narcotics, β-blockers, digoxin, ACE inhibitors, diuretics, oral hypoglycemics, met ormin, lithium, allopurinol, colchicine, amotidine, and ranitidine.

Anemia is a nearly universal complication o CKD. Increased blood loss with recurrent blood draws, higher risk o gastrointestinal (GI) bleeds, and decreased erythropoietin production promote anemia. Limiting packed red cell trans usions is important to avoid immune sensitization or patients who are candidates or kidney transplantation. Iron, B12, and olate de ciency should be excluded as contributing actors. The side e ects o oral iron o ten necessitate the use o intravenous iron. Newer ormulations o parenteral iron, such as iron sucrose and iron gluconate, have a lower anaphylactic risk than iron dextran. Recombinant erythropoietin therapy is critical in the management o anemia in CKD patients. These agents (erythropoietin and darbepoetin) are administered subcutaneously in outpatients with advanced CKD, and either intravenously or subcutaneously in ESRD patients on dialysis.

• Has the patient been educated about the available dialysis

■ ACUTE KIDNEY INJURY

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Patients with CKD are vulnerable to acute kidney injury (AKI) in the hospital, most o ten due to drug toxicity or ischemia. All medications prescribed to CKD patients must be reviewed or possible nephrotoxicity and dose adjusted or renal unction. Patients with CKD need care ul monitoring and ollow up a ter hospital discharge; renal unction o ten does not return to baseline a ter acute injury occurs. ACE inhibitors and ARBs should be stopped in the setting o AKI, but restarted upon its resolution, as these agents prevent progression o kidney diseases and have important cardiovascular bene ts.

■ HYPERKALEMIA Patients with CKD are at risk o hyperkalemia because o dietary indiscretion, medication e ects, or trans usion. Patients with ESRD will likely need dialysis to correct severe hyperkalemia, but the other treatment modalities still have a role, such as intravenous calcium or myocardial stabilization, and β-2 agonists and in usions o glucose and insulin to shi t potassium into cells. Bicarbonate therapy may be help ul in the setting o a nonanion gap metabolic acidosis. Potassium resin binders may be used as adjunctive therapy in CKD and ESRD patients, but are not a substitute or other therapies.

PRACTICE POINT

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2014

■ ADVERSE EVENTS FROM DRUG MISDOSING

ADEs occur in as many as 50% o hospitalized patients with CKD. Commonly misdosed drugs included antibiotics, acetaminophen, narcotics, beta-blockers, digoxin, ACE inhibitors, diuretics, oral hypoglycemics, met ormin, lithium, allopurinol, colchicine, amotidine, and ranitidine. Clinicians should review all medications including those prescribed as needed with attention to indication, sa ety, and dosing. I a narcotic is required or analgesia, it is pre erable to use agents that are not primarily excreted by the kidneys, such as entanyl and methadone. Certain antihypertensives ordinarily considered short-acting, such as hydralazine, may have unpredictable and prolonged antihypertensive e ects due to altered metabolism.

DIALYSIS PLANNING CHECKLIST IN PATIENTS WITH ADVANCED CKD

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modalities (in-center hemodialysis, peritoneal dialysis, or home hemodialysis)? For patients planned to start hemodialysis, have they been re erred or arteriovenous access placement? Have they been educated to avoid blood pressure checks, blood draws, and IVs in their non-dominant arm? Has the patient been educated about dietary restrictions (ie, daily uid intake, sodium, potassium, phosphorus)? Has a phosphorus binder been initiated i the serum phosphorous is > 5.5mg/dL? Has iron been repleted, and an erythropoietin-stimulating agent been started i the patient has severe anemia? Does the patient have immunity to hepatitis B?

SUGGESTED READINGS Adams JE. Dialysis bone disease. Semin Dialysis. 2002;15:277-289. Allon M. Dialysis catheter-related bacteremia: treatment and prophylaxis. Am J Kid Dis. 2004;44:779-791. Himmle arb J, Ikizler TA. Hemodialysis. N Engl J Med. 2010;363: 1833-1845. Hug BL, Witkowski DJ, Sox CM, et al. Occurrence o adverse, o ten preventable, events in community hospitals involving nephrotoxic drugs or those excreted by the kidney. Kidney Int. 2009;76:1192-1198. Madhukar M. The basics o hemodialysis equipment. Hemodial Internat. 2005;9:30-36. Palmer SC, Mavridis D, Navarese E, et al. Comparative e cacy and sa ety o blood pressure-lowering agents in adults with diabetes and kidney disease: a network meta-analysis. Lancet. 2015;385:2047-2056. Paulson WD, Ram SJ, Sibari GB. Vascular access: anatomy, examination, management. Semin Nephrol. 2002;22:183-194. Stevenson KB, Hannah EL, Lowder CA, et al. Epidemiology o hemodialysis vascular access in ections rom longitudinal in ection surveillance data: predicting the impact o NKF-DOQI clinical guidelines or vascular access. Am J Kidney Dis. 2002;39:549-555. Teitelbaum I, Burkart J. Peritoneal dialysis. Am J Kidney Dis. 2003;42: 1082-1096. Tonelli M, Pannu N, Manns B. Oral phosphate binders in patients with kidney ailure. N Engl J Med. 2010;362:1312-1324. Wang AY, Lai K. Use o cardiac biomarkers in end stage renal disease. J Am Soc Nephrol. 2008;19:1643-1652.

SECTION 16 Rheumatology

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Rheumatologic Emergencies Derrick J. Todd, MD, PhD Paul F. Dellaripa, MD

INTRODUCTION Rheumatologic diseases rarely present as an acute emergency. However, when they do, a delay in diagnosis can lead to signi cant morbidity and mortality. The most important and common examples o this include: (1) cervical spine involvement in in ammatory arthritides; (2) recognition o the protean presentations o giant cell arteritis so as to prevent permanent visual loss; (3) early diagnosis o pulmonary-renal syndromes which, i unrecognized, can lead to li ethreatening respiratory ailure and renal ailure; and (4) scleroderma renal crisis, in which a delay in diagnosis can mean the missing o the therapeutic window in which renal unction can be rescued. In each o these conditions, involvement o a rheumatologist is o ten warranted. THE CERVICAL SPINE IN THE RHEUMATIC DISEASES Catastrophic neurologic injury and even death may result rom cervical spine disease in patients with rheumatoid arthritis (RA) or spondyloarthritis (SPA). Early recognition o the signs and symptoms and appropriate diagnostic evaluation are critical to avoid these complications.

■ ATLANTOAXIAL INSTABILITY

Key Clinical Questions 1

What are the signs and symptoms o cervical spine involvement in rheumatoid arthritis and the spondyloarthritides?

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What tests should be ordered in patients with suspected pulmonary-renal syndrome?

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Which patients with interstitial lung disease are most likely to respond to corticosteroids?

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What are common and uncommon clinical signs and symptoms associated with giant cell arteritis?

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What actors portend an impending renal crisis in a patient with known scleroderma?

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What are the risk actors or Raynaud digital crisis? What treatments reduce morbidity?

Up to 30% o patients with severe RA have some degree o subluxation o the atlantoaxial joint (C1-C2). In normal patients, the odontoid process o the axis (C2) is secured in ront by the anterior arch o the atlas (C1), and posteriorly by the transverse ligament o the atlas. The normal distance between the odontoid process and the anterior arch o the atlas is 3 mm. In ammation in the small joints that make up the atlantoaxial joint, or tenosynovitis o the transverse ligament o the axis, may weaken the transverse ligament, as well as lead to bony erosions in the odontoid process. As a result, the space between the odontoid and the anterior arch o the atlas widens (Figure 246-1), and the atlantoaxial joint becomes unstable. Anterior subluxation, in which the atlas slides orward relative to the axis, is the most common type o cervical spine emergency. It leads to cord compression and cervical myelopathy. Less commonly, posterior subluxation occurs when the odontoid is badly damaged or ractured. Rarely, vertical C1-C2 subluxation occurs, with atlanto-axial impaction, migration o the odontoid into the oramen magnum, brainstem compression, and death. Atlantoaxial instability may also produce vertebrobasilar insu ciency by impairing blood ow in the vertebral arteries, which travel through the transverse oramina o the cervical spine. Symptoms o impending cervical spine subluxation may include occipital or retro-orbital headache, paresthesias o the extremities, and electric shock sensation in the upper extremities with neck exion. Physical examination ndings may include hyperre exia, a positive Babinski test, and sensory loss in the hands and eet. Typically, patients with advanced cervical spine disease also demonstrate evidence o advanced disease elsewhere. Un ortunately, the neurologic examination in patients with advanced or aggressive RA or SPA may be con ounded by muscle wasting, severe joint de ormities, and entrapment neuropathies. Ominous symptoms and signs include a sensation o the head alling orward during neck exion, syncope, respiratory irregularities, loss o sphincter control, dysphagia, hemiplegia, or nystagmus.

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complicated by atlantoaxial subluxation, as in RA. Arachnoiditis may lead to scarring o sacral and lumbar nerve roots and cauda equina syndrome, with saddle anesthesia, paraparesis, and bowel and bladder disturbances.

Figure 246 1 Cervical spine in rheumatoid arthritis, showing atlantoaxial subluxation. A lateral view of the upper cervical region shows posterior displacement of the odontoid process. In flexion view (left panel), preodontoid space measures approximately 5 mm (arrows). Normally this measurement should not exceed 2.5 to 3 mm in an adult, although in a child 4 to 5 mm may be within the normal range. The measurement is made at the mid-level of the anterior aspect of the dens with the neck held in flexion. Subluxation is not present on extension views (right panel). There is also severe disc space narrowing, sclerosis, and osteophyte formation at C5-C6 and C6-C7.

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AIRWAY INVOLVEMENT IN THE RHEUMATIC DISEASES

Lateral radiographs o the cervical spine in exion and extension are the most use ul initial diagnostic studies. These are diagnostic i the space between the anterior arch o the atlas and the odontoid is 9 mm or more, with an interval between the odontoid and the posterior arch o the atlas o less than 14 mm in the exed position. In symptomatic patients, exion and extension lms should only be per ormed i standard lms have excluded odontoid racture and severe subluxation. When cervical spine radiographs are not diagnostic, magnetic resonance imaging (MRI) or computed tomography (CT) scan should be per ormed. MRI is particularly use ul in delineating the extent o cord compression and the relationship o the odontoid to the brainstem, and in planning surgical stabilization. However, compared with exion/extension radiographs, MRI may underestimate the degree o subluxation because patients remain supine or the study. In the setting o progressive symptoms o cord compression, urgent neurosurgical consultation should be obtained or stabilization o the cervical spine. The role and timing o surgery in patients with atlantoaxial instability without cord compression is uncertain. The utility o medical therapy, such as rigid cervical collars and isometric neck strengthening exercises, is also unclear. In patients with RA undergoing general anesthesia, cervical spine lateral radiographs with exion and extension views should be obtained to exclude signi cant subluxation. Preoperative anesthesia consultation is mandatory in the RA patient with cervical instability. Fiberoptic intubation should be considered to limit neck manipulation.

■ SPINAL INVOLVEMENT IN THE SPONDYLOARTHRITIDES Neurologic mani estations are common in spondyloarthritis (SPA), particularly in ankylosing spondylitis. In longstanding disease, the spine is rigid, used, and brittle. Spinal racture may occur spontaneously or with minimal trauma. A dreaded complication is cervical racture, generally presented as acute neck pain, with or without neurologic compromise. Cord compression with quadriplegia may ensue unless the spine is promptly stabilized. Neurosurgical involvement is requisite. Ankylosing spondylitis may also be 2018

Airway involvement is a rare but signi cant source o morbidity and mortality in the rheumatic diseases. Granulomatosis with polyangitis (GPA, ormerly Wegener granulomatosis) is a systemic vasculitis characterized by granulomatous in ammation o the upper and lower respiratory tract and glomerulonephritis. Vasculitic in ammation may occur in the subglottis and proximal trachea. Tracheobronchial GPA o ten does not respond to traditional systemic therapy and may run a course independent o the other mani estations o GPA, leading to recurrent in ections or ventilatory obstruction. Tracheobronchial involvement should be suspected when a patient with known GPA presents with sore throat, cough, and di culty with secretions. Chest radiography and spirometry are help ul initial tests, which may be con rmed with laryngoscopy or CT scan. When this complication is suspected, otolaryngologic consultation is mandated. Treatment involves intralesional steroid injection and dilatation o obstructive lesions. When severe, stenting and tracheostomy may be necessary. Relapsing polychondritis (RP) is characterized by episodes o in ammation o the cartilaginous structures o the outer ear, nose, larynx, and tracheobronchial tree. Tracheobronchomalacia may result rom the loss o the supporting cartilage o the upper airway, resulting in either xed airway obstruction or hyperdynamic collapse. Concerning symptoms include progressive dyspnea, stridor, hoarseness, sore throat, and chest discom ort. The ow-volume loop is a use ul screening test. It may reveal dynamic extrathoracic or intrathoracic obstruction, or both. This may be con rmed with bronchoscopy or inspiratory/expiratory CT scanning. Treatment options include stenting, balloon dilatation, or tracheostomy.

■ PULMONARY-RENAL SYNDROMES Patients may present with both pulmonary in ltrates and renal insu ciency, and no obvious cardiac or in ectious cause. This should raise consideration o several diseases leading to pulmonaryrenal syndromes, especially when these patients have proteinuria or active urinary sediments to suggest glomerulonephritis. Pulmonary-renal syndromes may be immune complex-related, as in systemic lupus erythematosus (SLE) or cryoglobulinemia, or mediated by direct antibody binding, as in anti-glomerular basement membrane (anti-GBM) disease, also known as Goodpasture syndrome. Alternatively, pulmonary-renal syndromes may be pauciimmune, characterized by a relative lack o immunoglobulin and complement on histopathologic analysis. Pauci-immune conditions include the vasculitides associated with anti-neutrophilic cytoplasmic antibodies (ANCA), such as GPA, microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA, ormerly Churg-Strauss syndrome). Clinical clues may suggest a speci c diagnosis. Patients with SLE may also have arthritis, pleurisy, and photosensitivity. Patients with ANCA vasculitis may have sinusitis, otitis, or mononeuritis multiplex. Diagnostic evaluation in patients with pulmonary-renal syndrome should include testing or serum complement levels, ANCA, antinuclear antibodies (ANA), anti-GBM antibodies, and cryoglobulins. Use o cocaine contaminated with levamisole has been associated with a drug-induced ANCA vasculitis. Thus, it is prudent to include a toxicology screen or cocaine in patients presenting with an ANCA vasculitis syndrome. Biopsy o a ected tissue (usually kidney) should be strongly considered or most patients presenting with pulmonary-renal syndromes. In the ace o undi erentiated disease

VISION LOSS IN GIANT CELL ARTERITIS Giant cell arteritis (GCA) is a large-vessel vasculitis that most o ten a ects branches o the external carotid arteries. GCA must be recognized and treated promptly, as patients may su er irreversible vision loss. Although patients may be as young as 50 years old, most are o age 60 or older. In addition, most patients are o Northern European ancestry. GCA is the most common systemic vasculitis in older adults, but it is still relatively rare. Among patients age 50 or older, incidence rates are reported at 20 to 30 cases per 100,000 patients in Northern European countries. GCA occurs at an even lower requency in nonwhite patients, with estimates as low as 1 case per 100,000. Temporal arteritis is a term used to describe vasculitis o the temporal artery, which is common in GCA. Cranial symptoms o GCA include headache, scalp tenderness, jaw claudication, and visual disturbances. Involvement o the thoracic great vessels may cause upper-extremity claudication. Aortitis may mani est years a ter the initial diagnosis and treatment o GCA. Patients present with signs and symptoms o aortic aneurysm or dissection. GCA may sometimes present as a chronic cough, ailure to thrive, and ever o unknown origin in an elderly patient. Most patients also experience atigue, anorexia, and weight loss. GCA may coexist with polymyalgia rheumatica (PMR), a condition that causes achiness and sti ness o the shoulder and hip girdle, worse in the morning, and associated with atigue. Patients with established PMR have an approximately 10% risk o developing GCA at some point in their lives, even years a ter the diagnosis and treatment o PMR.

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Ophthalmologic evaluation is mandatory in patients with suspected GCA. It may reveal evidence o anterior ischemic optic neuropathy, retinal artery occlusion, or choroidal in arction. The remainder o the physical examination may reveal subtle clues o arteritis. Tender, tortuous temporal arteries are a classic but unreliable nding. A chest bruit, aortic insu ciency murmur, or discrepant upper-extremity blood pressures signal thoracic vessel involvement. Patients with concurrent PMR may have bursitis o the shoulders and hips, with pain ul limited range o motion in these joints. The diagnosis o GCA is based on the clinical presentation, with corroborative pathologic ndings o arteritis. The temporal artery is the most easily accessible extracranial artery or biopsy. Temporal artery biopsy is a high-yield, low-risk procedure. There is an emerging role or arterial ultrasound in patients with suspected GCA, although this test does not replace the role o biopsy. There is no single blood test diagnostic or GCA. Markedly elevated acutephase reactants are suggestive, but nonspeci c. The erythrocyte sedimentation rate (ESR) may be as high as 100 mm/h, a value ound in ew other disease states (Table 246-1). However, normal acute phase reactants have been rarely reported in patients with GCA. Anemia o chronic disease and thrombocytosis may also be present. Classi cation criteria exist or GCA (Table 246-2). These were designed primarily or use as inclusion criteria or research studies, rather than or everyday clinical practice. Certainly, there are patients with GCA who do not meet these criteria. The diagnosis o GCA should be considered in any elderly patient who presents with recent-onset headaches, visual complaints, and unexplained elevated acute phase reactants. In these instances, empiric corticosteroid treatment should be started immediately, and temporal artery biopsy should be arranged expeditiously. Empiric corticosteroids do not alter pathologic ndings, provided that the artery in question is sampled within 10 to 14 days o initiating treatment. Neither visual disturbances nor abnormal ophthalmologic exam need to be present to warrant immediate action. The retina is exquisitely sensitive to ischemia, and patients with GCA are unlikely to recover vision once it is lost. Treatment consists o corticosteroids in the equivalent o prednisone 1 mg/kg daily. Intravenous (pulse) corticosteroids have not been proven more

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Interstitial lung disease (ILD) complicates a variety o rheumatic diseases including scleroderma, dermatomyositis/polymyositis (DM/ PM), SLE, RA, Sjögren syndrome, and mixed connective tissue disease (MCTD). ILD a ects up to 50% o patients with scleroderma, 30% o patients with DM/PM, and 10% o patients with RA. While parenchymal lung disease is o ten insidious, in some cases it may be explosive and require hospitalization. Patients may present with dry cough, progressive dyspnea, and desaturation with exercise oximetry. High-resolution chest CT scan is use ul in characterizing ILD. It may reveal ground glass opacities, seen in many other conditions including acute interstitial pneumonia, nonspeci c interstitial pneumonia, desquamative interstitial pneumonia, Pneumocystis jiroveci pneumonia (PCP), viral pneumonia, pulmonary edema, and acute respiratory distress syndrome. Honeycombing and traction bronchiectasis are seen in brotic lung disease and usual interstitial pneumonia, and consolidative in ammatory lung disease is seen in cryptogenic organizing pneumonia. However, there is much overlap in the radiographic appearance o di erent orms o ILD. Lung biopsy may be diagnostic, although the potential utility o a histopathologic diagnosis must be balanced against the hazards o lung biopsy in patients with tenuous respiratory status. Treatment or in ammatory lung disease involves high-dose corticosteroids with immunomodulating agents such as cyclophosphamide, azathioprine, mycophenolate mo etil, or calcineurin inhibitors, such as cyclosporine and tacrolimus. Fibrotic lung disease may require lung transplantation in suitable patients. In patients with worsening respiratory symptoms already on immunosuppressive regimens, bronchoscopy should be strongly considered to exclude concurrent superimposed opportunistic in ection. In patients on high-dose corticosteroids or ILD with or without a second agent, prophylaxis against PCP should be strongly considered.

Polymyalgia rheumatica Giant cell arteritis and other vasculitides Adult-onset Still’s disease In ectious endocarditis Osteomyelitis Septic arthritis Multiple myeloma

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■ INTERSTITIAL LUNG DISEASE

TABLE 246-1 Select Conditions Associated with Erythrocyte Sedimentation Rate ≥100 mm/hour

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and clinical deterioration, empiric therapy including high-dose corticosteroids and even cyclophosphamide or rituximab may be necessary, pending the results o testing or biopsy.

TABLE 246-2 Classification Criteria for Giant Cell Arteritis Age 50 or older New-onset headache Temporal artery tenderness Erythrocyte sedimentation rate 50 mm/hour or greater Histopathology showing arteritis Classi ication o GCA is met i patient has three or more o the above criteria.

2019

COMPLICATIONS OF SCLERODERMA The term scleroderma encompasses both localized scleroderma (morphea or linear scleroderma) and systemic sclerosis. Localized scleroderma a ects only the skin and is not discussed urther here. In this chapter, the term scleroderma will be used interchangeably with the term systemic sclerosis. Scleroderma is characterized by autoimmunity, vasculopathy, and systemic brosis. Vascular complications include pulmonary hypertension, scleroderma renal crisis, cutaneous calcinosis, and telangiectasia o the skin or gastrointestinal (GI) tract. Progressive brosis may involve the skin, GI tract, lungs, heart, or other organs. This section ocuses on two emergencies in patients with scleroderma: scleroderma renal crisis and Raynaud crisis (seen most o ten in, but not limited to, patients with scleroderma).

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e ective or patients with GCA, but are an option or patients with threatened vision. Since luminal thrombosis o the ophthalmic artery is thought to be the event that precipitates blindness in GCA, low-dose aspirin may also be added to the therapeutic regimen. Once a patient starts treatment with corticosteroids, vision is o ten spared i it has not already been a ected. Threatened vision is the most common emergency situation that may arise in GCA. In addition, aortitis may require emergent corticosteroids or even surgical intervention to reduce the risk o dissection or rupture. All cases o suspect or proven GCA warrant rheumatologic consultation or long-term management o disease.

■ SCLERODERMA RENAL CRISIS Scleroderma renal crisis (SRC) usually develops within 5 years o diagnosis o scleroderma. It may even be the presenting eature o scleroderma, o ten in patients with other signs o scleroderma that have eluded diagnosis, such as Raynaud syndrome, sclerodactyly, cutaneous brosis, organ brosis, and telangiectasia. Rapidly progressive skin disease and prior corticosteroid usage are major risk actors or renal crisis. SRC usually presents as hypertension and progressive renal insu ciency in a patient with scleroderma. Patients may have symptoms o malignant hypertension: headache, visual disturbances, pulmonary edema, and encephalopathy. Progression to hypertensive crisis, overt renal ailure, and death is rapid without prompt recognition and treatment. SRC is a microangiopathy o the renal vasculature, not a orm o glomerulonephritis. Urinalysis may reveal proteinuria and hematuria, but red blood cell casts are typically absent. The renal vasculopathy causes endothelial shearing o erythrocytes that may be detected as a microangiopathic hemolytic anemia (MAHA), with schistocytes on peripheral blood smear analysis and mild thrombocytopenia. As SRC may be the presenting eature o scleroderma, it should always be considered part o the di erential diagnosis in a patient with unexplained renal dys unction and MAHA eatures (Table 246-3). Renal biopsy does not distinguish SRC rom other microangiopathies, but it may be use ul to exclude glomerulonephritis. Ultimately, the diagnosis o SRC is a clinical one based on progressive hypertension, renal dys unction, proteinuria, and MAHA in a patient with systemic eatures o scleroderma. Angiotensin-converting enzyme (ACE) inhibitors are the mainstay o treatment. This is the only condition in which overt renal ailure is treated with aggressive ACE inhibitor therapy, so one must have reasonable diagnostic certainty be ore initiating treatment. While any ACE inhibitor is likely to be e ective, captopril has the largest body o supportive evidence, it is rapidly e ective, and doses can be escalated rapidly. Enalapril has the advantage o intravenous dosing in exceptional circumstances. The goal o therapy should be normalization o blood pressure within a ew days o starting treatment. This o ten requires hospitalization or

2020

TABLE 246-3 Causes of Microangiopathic Hemolytic Anemia with Renal Failure Scleroderma renal crisis Antiphospholipid antibody syndrome Hemolytic uremic syndrome Thrombotic thrombocytopenic purpura Heparin-induced thrombocytopenia Malignant hypertension Di use intravascular coagulation HELLP syndrome (Hemolysis, Elevated Liver enzymes, Low Platelets) Trans usion reactions Drugs (most o ten chemotherapeutic agents)

close monitoring and dose adjustment o drugs. O ten, serum creatinine values will lag in their improvement, and ACE inhibitor therapy should continue undeterred by rising creatinine values. There is ar less experience with angiotensin receptor blockers (ARBs) in SRC, and ACE inhibitors should be used whenever possible. In patients with ACE-inhibitor-induced angioedema, allergy consultation should be sought or possible desensitization. Despite these measures, upwards o 40% o patients with SRC require dialysis or progressive renal ailure. Concurrent pulmonary or cardiac scleroderma o ten precludes renal transplantation or SRC-related end-stage renal disease. Notably, it is not unusual or renal unction to recover in patients with SRC a ter months or even years o dialysis, provided that ACE inhibitor therapy is continued unabated. Even so, patients with SRC have a 5-year mortality rate that approaches 40%, mostly because SRC portends aggressive extrarenal scleroderma.

■ RAYNAUD CRISIS Primary Raynaud phenomenon (RP) is a common, usually benign, condition o cold-induced pain, pallor, and cyanosis o the digits, occurring in the absence o systemic connective tissue disease (CTD). Primary RP represents an exaggeration o normal physiologic vasoconstriction in response to cold. Secondary RP is a more aggressive version o RP that is associated with systemic CTDs like scleroderma, DM/PM, SLE, RA, Sjogren syndrome, and MCTD. A Raynaud crisis occurs when an episode o prolonged digital ischemia, lasting longer than 30 to 60 minutes despite rewarming, threatens the viability o one or more digits. It is a medical emergency that requires prompt intervention to reverse vasoconstriction and restore blood ow. Raynaud crisis most o ten complicates secondary Raynaud phenomenon, and not primary RP. Occurrence o a Raynaud crisis in a patient without known CTD should prompt a diagnostic workup or one. Primary RP a ects upwards o 10% to 20% o young women. It is much less common in men and the elderly. A typical episode involves a classic series o color changes. Digits rst turn white in a demarcated ashion, as digital arteries vasoconstrict in response to cold (Figure 246-2). With prolonged vasoconstriction, digits become blue or purple because o tissue cyanosis. Finally, digits turn pinkish-red, as blood ow is restored, and the episode resolves. RP may also be triggered by stress or rapid changes in ambient air temperature, as upon entering an air-conditioned room on a warm day or reaching into a re rigerator or reezer. O note, patient sel -reporting o cold hands without color changes ails to satis y the clinical diagnosis o RP. In patients with RP, episodes may involve all the digits or may be limited to a single digit (or part o a digit). Involved digits are o ten achy, numb, or even

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Acquired distal tubular acidosis is ound in about 30% o patients with Sjögren syndrome, probably due to loss o the luminal H(+)ATPase pump rom the intercalated cells o the collecting duct. This is clinically silent in most patients. However, it may sometimes lead to potassium wasting and weakness, and even be severe enough to present with hypokalemic paralysis, quadriparesis, and respiratory ailure. The prognosis is good with aggressive potassium replacement in the short term and oral supplementation o potassium and bicarbonate in the long term.

pain ul. Prolonged ischemia can lead to digital ulcerations or even a threatened digit. Primary RP occurs in the absence o an underlying disease, and rarely has major sequelae. In contrast, secondary RP is associated with one or more o the conditions listed in Table 246-4. Many o these conditions are CTDs that are associated with vasculopathy and endothelial dys unction. These actors contribute to the aggressiveness o secondary RP, which is more likely to produce severe symptoms, digital ulcers, or Raynaud crisis. Common drugs, such as ca eine, cocaine, amphetamines, pseudoephedrine, nicotine, and beta-blockers, can exacerbate arterial vascoconstriction in either primary or secondary RP. Patients with RP should be advised to avoid these drugs, and educated about signs and symptoms o a Raynaud crisis and the need to seek medical attention i it develops.

TABLE 246-4 Diseases and Conditions Associated with Secondary Raynaud Phenomenon Category Rheumatologic diseases

Disease Entity Scleroderma Systemic lupus erythematosus Rheumatoid arthritis Sjögren syndrome Dermatomyositis/polymyositis Mixed connective tissue disease Vasculitis, including cryoglobulinemia Behçet disease Thromboangiitis obliterans Other orms o vascular injury Vibration-induced vasculopathy Radiation-induced vasculopathy Paraneoplastic vasculopathy Frostbite Drugs including chemotherapy and cocaine Ergotamines

t o l o g i c E m e r g e n c i e s

Figure 246 2 Raynaud phenomenon, with digital pallor and cyanosis. (Reproduced, with permission, rom Wol K, Goldsmith LA, Katz SI, et al. Fitzpatrick’s Dermatology in General Medicine, 7th ed. New York, NY: McGraw-Hill; 2008. Fig. 171-1.)

History and physical examination is o ten su cient to distinguish primary RP rom secondary RP. In the absence o previously identied CTD, secondary RP is suggested by ischemic episodes lasting longer than 30 to 60 minutes, recurring RP isolated to a single digit, eatures o scleroderma, or pitting digital scars. Positive serologic tests or ANA or other autoantibodies and an abnormal nail old capillary microscopy help to secure a CTD diagnosis. Nail old capillary microscopy can be per ormed without special instruments. For example, an ophthalmoscope may be used to inspect a nailbed that has been coated with a drop o mineral oil or even a clear bactericidal hand cleanser. Abnormal ndings include dilated capillary loops, tortuous vessels, hemorrhage, or vessel dropout. Raynaud crisis must be distinguished rom other causes o digital ischemia, such as vascular trauma, vasculitis, proximal vessel stenosis, thromboangiitis obliterans, antiphospholipid antibody syndrome, atherosclerosis, and microembolic disease. The Allen test may be used at the bedside to assess or patency o both radial and ulnar arteries. Examination o pulses with Doppler ultrasound may help exclude proximal vascular occlusion. In selected instances, magnetic resonance angiography or even traditional vascular angiography may be necessary to con rm that the arterial stricture is at the level o the digital arteries, and not more proximal. Even then, it may be di cult to exclude digital microemboli, and proximal sources o emboli may sometimes need to be sought. The goal o management in a Raynaud crisis is to reduce vascular contractility and restore blood ow to ischemic digits. Patients should be kept in a warm, stress- ree environment to minimize urther vasomotor stimuli. A ected digits should be reheated in tepid water; hot water should be avoided, as it may urther damage ischemic tissue. Oxygen levels should be optimized, bearing in mind that pulse oximetry o a digit a ected by RP is unreliable. Narcotic analgesia may reduce vasoconstriction induced by pain. Aspirin and sometimes heparin may lessen the risk o thrombosis within vasospastic vessels. Antihypertensive agents are typically used or initial vasodilator therapy. Dihydropyridine-class calcium channel blockers, such as short-acting or extended-release ni edipine or amlodipine may be o some bene t, but hypotension may be dose-limiting. Alpha-blockade with prazosin or doxazosin is o ten more e ective, but hypotension may also be problematic. Oral hydralazine and transdermal nitroglycerin placed proximal to the part o the extremity involved may provide temporary relie , but tachyphylaxis and rebound vasospasm may occur. Anesthesia consultation may be required or chemical block o sympathomimetic nerves locally or cervically. Endothelin receptor antagonists, such as bosentan and ambrisentan, improve the healing rate o digital ulcers in patients with RP, but their role in Raynaud crisis has not been de nitively established. In severe, re ractory cases, digital sympathectomy, epoprostenol in usions, or phosphodiesterase inhibitors such as sildena l and botulinum toxin injections may be attempted with the help o consultant services. Despite these e orts, patients may still experience digital necrosis and require amputation; it is advisable

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to involve vascular surgery whenever a patient presents with a Raynaud crisis.

2022

DRUG TOXICITY IN THE RHEUMATIC DISEASES While allopurinol is a generally well-tolerated medication or hyperuricemia, it is occasionally associated with serious toxicity. Allopurinol hypersensitivity syndrome ranges rom a minor rash to a li e-threatening systemic illness, with eatures o toxic epidermal necrolysis or Stevens-Johnson syndrome. It typically starts several weeks a ter drug initiation. Risk actors include renal insu ciency and rapid dose-escalation o allopurinol. In addition to rash, allopurinol hypersensitivity may also eature ever, eosinophilia, and acute hepatitis. Renal insu ciency, while not a typical side e ect o allopurinol, can be a eature o allopurinol hypersensitivity. Treatment o allopurinol hypersensitivity includes administration o corticosteroids and cessation o allopurinol. In minor cases, patients may be rechallenged with allopurinol, but only under the direction o a specialist. Rechallenge should be generally avoided in patients with a history o severe allopurinol hypersensitivity reaction. Allopurinol can also rarely cause a severe ANCA-positive vasculitis. This generally improves upon drug cessation, although some cases require treatment similar to the ANCA-associated vasculitides. Allopurinol also inhibits the metabolism o azathioprine and 6-mercaptopurine (6-MP), increasing the risk o toxicity rom these agents. The combination o allopurinol and these agents should be avoided i possible; i not, azathioprine or 6-MP dosing should be reduced to 25% o normal when using these agents concomitantly, under the direction o specialists. Methotrexate (MTX) is among the most commonly used immunosuppressive medications in rheumatology. Toxicity may involve liver, kidneys, mucous membranes, and, in less than 1% o cases, the lungs. Pulmonary toxicity associated with MTX usually presents in the rst year o use, with dry cough, dyspnea, ever, and, in severe cases, hypoxemia and respiratory ailure. Alveolar or interstitial in ltrates may be seen on chest radiography or CT, although imaging may be unrevealing early in the course. The di erential diagnosis includes community-acquired pneumonia, opportunistic in ection, and progressive ILD rom the underlying rheumatic disease itsel . Bronchoscopy or induced sputum is o ten necessary to exclude opportunistic in ection. Treatment in mild cases entails cessation o MTX. Corticosteroids or other immunosuppressive therapies may be necessary in severe cases. MTX overdose, whether accidental or intentional, is potentially li e-threatening because o bone marrow suppression, nephrotoxicity, and hepatotoxicity. Hemodialysis does not e ectively clear MTX. Early recognition o MTX overdose is critical in order to initiate olinic acid as a rescue therapy. Cyclophosphamide (CYP) is an alkylating agent requently used in the treatment o vasculitis and severe lupus. Major side e ects include neutropenia and lymphopenia, which may lead to severe immunosuppression and overwhelming in ection, especially with

opportunistic pathogens such as ungi and PCP. CYP may also cause hemorrhagic cystitis, and it increases the li etime risk o urinary tract cancer. The dose should be adjusted in the elderly and or renal unction to avoid toxicity. Azathioprine is a purine analogue used in a variety o rheumatic syndromes. It may cause severe neutropenia, in ection, and transaminitis. Patients with low or absent activity o the enzyme that metabolizes azathioprine, thiopurine methyltrans erase (TPMT), are at increased risk or cytopenias and other toxicities. Genetic testing or TPMT is available and o ten obtained in patients starting azathioprine. Azathioprine has a number o problematic drug interactions, including ACE inhibitors, allopurinol, and other immunosuppressive drugs. It should be dose-adjusted in the elderly and in those with renal insu ciency.

SUGGESTED READINGS Brown KK. Rheumatoid lung disease. Proc Am Thorac Soc. 2007;4:443-448. Chif ot H, Fautrel B, Sordet C, Chatelus E, Sibilia J. Incidence and prevalence o systemic sclerosis: a systematic literature review. Semin Arthritis Rheum. 2008;37:223-235. Denton CP, Lapadula G, Mouthon L, Muller-Ladner U. Renal complications and scleroderma renal crisis. Rheumatology (Oxford). 2009;48(30):32-35. Ernst A, Ra eq S, Boiselle P, et al. Relapsing polychondritis and airway involvement. Chest. 2009;135:1024-1030. Fathi M, Vikgren J, Boijsen M, et al. Interstitial lung disease in polymyositis and dermatomyositis: longitudinal evaluation by pulmonary unction and radiology. Arthritis Rheum. 2008;59:677-685. Hunder GG. Epidemiology o giant-cell arteritis. Clevel Clin J Med. 2002;69(2):79-82. Kim DH, Hillibrand AS. Rheumatoid arthritis in the cervical spine. J Am Acad Orthop Surg. 2005;13:463-474. Krause ML, Cartin-Ceba R, Specks U, Peikert T. Update o di use alveolar hemorrhage and pulmonary vasculitis. Immunol Allergy Clin North Am. 2012;32:587-600. Mouthon L, Bussone G, Berezné A, et al. Scleroderma renal crisis. J Rheumatol. 2014;41:1040-1048. Specks U. Di use alveolar hemorrhage syndromes. Curr Opin Rheumatol. 2001;13:12–17. Tashkin DP, Elasho R, Clements PJ, et al. Cyclophosphamide versus placebo in scleroderma lung disease. N Engl J Med. 2006;354:2655–2666. Weyand CM, Gorozny JJ. Giant cell arteritis and polymyalgia rheumatica. N Engl J Med. 2014;371:50-57.

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CHAP TER

Gout, Pseudogout, and Osteoarthritis

INTRODUCTION Gout, pseudogout, and osteoarthritis make up the largest portion o the rheumatic diseases that a ect primarily joints. Although these three disease entities are quite distinct, they share a number o eatures in common: all tend to be diseases seen at older ages; all three are o ten seen in overlap with each other; and all three are characterized primarily by in ammatory and/or mechanical abnormalities, rather than autoimmune ones. Whereas gout and pseudogout are diseases o abnormal crystal ormation and resultant in ammation, osteoarthritis is primarily a disease o mechanically driven, biochemically propagated cartilage loss and autodestruction. In the ollowing sections, we discuss these three important diseases, their pathogenesis, and management. GOUT

Robert T. Keenan, MD, MPH Svetlana Krasnokutsky, MD, MS Michael H. Pillinger, MD

Key Clinical Questions 1

Why do patients have acute lares o crystal arthropathies?

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How is gout distinguished rom other monoarthropathies?

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What are the appropriate therapies or acute and chronic gout and pseudogout?

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What are the pathophysiologic eatures o osteoarthritis (OA), and how do these relate to clinical mani estations?

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How is OA di erentiated rom other types o arthritis?

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What are the nonpharmacologic, pharmacologic, and surgical treatment options or OA?

Gout currently a ects more than 8 million Americans, usually presenting with severe acute episodic arthritis that may evolve over time into chronic destructive tophaceous disease. Gout is more common in men (6.1 million US males vs 2.2 million US emales), and is slightly more common among A rican Americans (5% o the A rican American population vs 4% o the US white population). The prevalence o gout rises with age, rom 3.3% among individuals 40 to 49 years old, to 8.0% among individuals 60 to 69, to as high as 12.6% in those 80 years and older. The annual incidence o gout rose rom 4.5 per 10,000 in 1977 to 1978 to 6.4 per 10,000 in 1995 to 1996, and to 12.4 per 10,000 rom 1994 to 2007. Overall, the prevalence o gout has more than quadrupled over the past hal century. Despite being the most common in ammatory arthropathy, gout is requently misdiagnosed and mismanaged.

■ PATHOPHYSIOLOGY The most important risk actor or gout is hyperuricemia, or an excess o serum urate, the end product o purine metabolism. Serum urate concentrations are determined by the balance between urate production and elimination; hyperuricemia may be caused by either overproduction or underexcretion o urate, or a combination o both. Consumption o meat or sea ood promotes hyperuricemia and gout as a result o the high-purine content o these oods. In contrast, alcohol consumption increases urate production through multiple mechanisms, including generation and turnover o ATP (a purine base), diuresis and dehydration, production o lactic and ketoacids (which block renal urate excretion), and the consumption o purines in alcoholic beverages. Beer and ale ingestion are most strongly correlated with hyperuricemia and gout (presumably because o their higher-purine content), while hard liquor increases serum urate and gout risk to an intermediate degree. Moderate wine consumption has a lesser e ect on serum urate and the risk o gout, possibly because o other compounds present in wine. In history, the high prevalence o gout in a uent drinkers o wine and port may have been related to the use o lead acetate by wine merchants as a preservative and sweetener; chronic lead poisoning causes tubulointerstitial kidney disease that promotes hyperuricemia (saturnine gout) (Table 247-1). More than 100 years ago Osler suggested that sugar intake might increase the risk o gout; recent studies prove Osler to have been correct. Gout prevalence has increased over the last 50 years, concomitant with the introduction and rising consumption o high- ructose corn syrup as a sweetener in prepared oods. Human 2023

Urate-Increasing Agents Foods Meat, sea ood (high in purines) Alcoholic beverages Fructose Metabolites Lactate β-hydroxybutyrate, Acetoacetate Drugs Pyrazinamide Nicotinate Salicylates (low dose) Diuretics Cyclosporine Tacrolimus Ethambutol β-blockers

Urate-Decreasing Agents Foods Dairy products Uricosurics Lesinurad Probenecid Sul inpyrazone Salicylate (high dose) Losartan Benzbromarone Feno ibrate Amlodipine Xanthine oxidase inhibitors Allopurinol Febuxostat Uricase (rasburicase, pegloticase)

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TABLE 247-1 Substances That Affect Urate Levels

2024

metabolism and degradation o ructose generates urate to a greater degree than occurs with other sugars. In addition, ructose may have other hyperuricemia-inducing e ects, by virtue o its ability to modulate urate transport in the kidney. In contrast, dairy consumption appears to be protective against hyperuricemia, perhaps because o the uricosuric e ect o milk proteins such as casein. Uric acid is eliminated rom the body by both gastrointestinal and renal routes. Approximately one-third o urate elimination occurs through the gastrointestinal system, in saliva, gastric juices, pancreatic secretions, and direct loss rom the bowel. The remaining two-thirds o urate excretion is via glomerular ltration and a complex balance o tubular secretion and reabsorption in the kidneys. Urate is reely ltered by the glomerulus, but 90% or more is reabsorbed. Tubular handling o urate is carried out via several organic anion transporters (OATs). Genomewide association studies have expanded our understanding o urate metabolism, and have identi ed genes that encode urate transporters in the kidney as well as the gut. Important genes involved in renal reabsorption o urate include SLC22A12 (encodes URAT1, a reabsorbing transporter) and SLC2A9 (encodes GLUT9 transporter). A number o agents that lower serum urate, such as probenecid, act by inhibiting URAT1 to promote renal urate excretion. In contrast, the ABCG2 gene has been ound to encode the BRCP transporter, which promotes the renal tubular excretion o urate. Patients with genetic de ects in BRCP tend to have reduced renal urate excretion, and increased serum levels o urate. Hyperuricemia is considered either primary (related to intrinsic qualities o the individual) or secondary (acquired). The vast majority o gout patients have primary hyperuricemia, which may be compounded by secondary disease. About 90% o gout patients are primary underexcreters, with genetic molecular de ects in renal urate excretion. Most o these patients have otherwise normal renal unction. Primary overproduction accounts or the remaining 10% o primary hyperuricemia. Some patients who are primary overproducers have complete (Lesch-Nyhan syndrome) or partial (Kelly-Seegmiller syndrome) de ciency in hypoxanthine phosphoribosyltrans erase (HPRT), the rate-limiting enzyme responsible or the salvage o degraded purines or reuse. All patients with

Lesch-Nyhan syndrome, and some with Kelly-Seegmiller syndrome, also have neurocognitive de cits that are independent o their serum urate levels. Secondary hyperuricemia occurs in acquired conditions that result in decreased urate excretion or increased urate generation. Acute or chronic renal insuf ciency may impair urate excretion. Diseases o increased cell turnover, such as malignancies and hemolytic anemia, result in high urate production. Hyperuricemia can rarely mani est in the early teens due to a group o autosomal dominant diseases, which include amilial juvenile hyperuricemic nephropathy (FJHN) and medullary cystic kidney type II disease. These diseases eature a mutant gene that interrupts the tertiary structure o uromodulin, also known as Tamm-Hors all protein. The clinical presentation o these diseases not only includes early-onset gout, but also progressive renal ailure and polyuria.

■ NATURAL HISTORY Gout has traditionally been considered to occur in our progressive stages. In asymptomatic hyperuricemia, the risk o an acute gout attack increases as the level o uric acid rises past its solubility point (> 6.8 mg/dL). Once solubility is exceeded, monosodium urate crystals may precipitate in joint spaces and lead to acute gouty arthritis. During this stage, the innate immune system initiates a cascade o events in response to the crystals, including activation o complement and resident joint tissue macrophages, and recruitment o neutrophils rom the bloodstream. The in ammasome, an intracellular assembly in macrophages that activates interleukin-1β (IL-1β), has recently been implicated in the in ammatory response to uric acid crystals. IL-1β in turn stimulates the production o other in ammatory mediators, including tumor necrosis actor (TNF)-α, IL-6, IL-8, and prostaglandin E2. The result is severe local in ammation as well as a systemic response to cytokine release, including low-grade ever and elevated acute phase reactants. Acute gout attacks are exquisitely pain ul but typically sel -limited, even without therapy, apparently because o in ammatory autoregulation. The asymptomatic interval between acute gouty attacks is known as intercritical gout. Over time attacks tend to come more requently, the intercritical period dwindles, and chronic tophaceous gout may develop. Tophi are aggregates o urate crystals, typically accompanied by a low-level chronic in ammatory state. They are actually complex structures, consisting o a mix o monosodium urate crystals and cellular debris surrounded by activated macrophages and other immune cells. Although tophi are most obvious when they occur in the periarticular so t tissues, they may also develop in cartilage and bone. Crystal deposition may result in a number o chronic syndromes o pain and disability (Table 247-2). Radiographic images o tophi in periarticular bone reveal the pathognomonic nding o punched-out erosions with sclerotic margins and overhanging edges (Figure 247-1). Recently, more sensitive imaging using ultrasound, magnetic resonance imaging (MRI) or dual-energy computed tomography (CT) have suggested that occult tophi are much more common that previously appreciated, and o ten orm even be ore the onset o the initial acute gout attack, providing a readily available source o crystals or uture acute attacks.

■ DIAGNOSIS AND DIFFERENTIAL DIAGNOSIS The gold standard or the diagnosis o gout is needle aspiration o acutely or chronically in amed joints or tophi, ollowed by polarized light microscopy to identi y negatively bire ringent, needle-shaped crystals (uric acid crystals). The presence o such crystals, particularly when seen intracellularly within in ltrating neutrophils, con rms the diagnosis o an acute attack and helps to distinguish gout rom septic arthritis, pseudogout, and other causes o in ammatory joint disease. Extracellular crystals alone

C H A P T E R 2 4 7 G o u t , P s e u d o g o u t , a n d O s t e o a r t h r i t

are diagnostic o gout, but not necessarily an acute gouty attack; in patients with established gout, previously ormed crystals may persist even a ter in ammation has resolved, residing as innocent bystanders in the setting o other joint pathologies. The sensitivity o synovial uid analysis or demonstrating negatively bire ringent crystals in patients with acute gouty arthritis is at least 85%, with a speci city approaching 100%. In contrast, the speci city o a clinical diagnosis o gout is signi cantly lower, and septic arthritis and pseudogout are o ten misdiagnosed as gout. There ore, in almost all circumstances, diagnostic arthrocentesis should be per ormed i possible, especially in the hospital setting. As acute gout may coexist with other joint pathology, a wider evaluation is almost always warranted, even in the presence o intracellular, negatively bire ringent crystals. In addition to crystal

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Acute monoarthritis or polyarthritis Bursitis Tendonitis Tophaceous deposits (including vertebrae) Enthesitis Synovial osteochondromatosis Pseudoankylosing spondylitis Carpal tunnel syndrome Tendon rupture Joint destruction Pseudorheumatoid arthritis Spinal stenosis Crown dens syndrome In lammatory osteoarthritis

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TABLE 247-2 Musculoskeletal Manifestations of Crystal-Induced Arthropathy

analysis, synovial uid should always be sent or cell count with di erential, Gram stain, and culture. Grossly, synovial uid is typically straw colored and varies rom translucent to opaque. Synovial uid cell counts in gout may range rom 2000 to >100,000 per mm 3, with greater than 50% neutrophils (o ten approaching 90%). Serum uric acid should also be obtained during an acute attack, and a high serum urate supports the possibility o a diagnosis o gout. However, patients may be hyperuricemic without having gout, and serum urate levels in gout patients may be transiently normal or low during an acute attack due to an increase in renal excretion (an e ect o the cytokine IL-6 on the kidney). Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) are typically elevated during a gout attack, but this nding is nonspeci c. Urinary uric acid collections should not be obtained during gout attacks; they are neither use ul nor reliable in the acute period. Radiographs in the acute setting typically show only nondescript so t tissue swelling, but radiographic evidence o erosions can conrm chronic disease. Musculoskeletal ultrasound (MSUS) may visualize intraarticular crystal deposits, with a characteristic hyperechoic enhancement o the outer sur ace o the hyaline cartilage, known as the double contour sign. MSUS may prove to be an alternative method or the diagnosis o the crystal arthropathies, but limitations include the inability to distinguish the presence or absence o in ection. Advanced imaging technologies such as dual energy computed tomography (DECT) and improved magnetic resonance imaging can also play a role in the diagnosis and di erentiation o gout rom other in ammatory arthropathies, but availability and cost limit their current clinical utility. The di erential diagnosis or acute gout includes conditions generally associated with acute monoarthritis, such as pseudogout and septic arthritis, as well as conditions leading to oligoarthritis and polyarthritis, such as reactive arthritis, psoriatic arthritis, and even rheumatoid arthritis. Ideally, a crystal diagnosis o gout should be the goal; i this is not possible, the diagnosis o acute gouty arthropathy should be made by a combination o historical and clinical criteria. A thorough history will help distinguish an acute gout attack rom other causes o acute arthritis. Some o the previously proposed clinical, radiographic, and laboratory criteria include (1) a history o one or more episodes o monoarticular arthritis, ollowed by intercritical periods completely ree o symptoms (may not be applicable in the acute hospital setting); (2) maximum in ammation within 24 hours o onset o the attack; (3) rapid resolution a ter initiation o colchicine or a nonsteroidal anti-in ammatory drug (NSAID); (4) unilateral rst metatarsophalangeal joint involvement (podagra), especially during a rst event; (5) hyperuricemia; and (6) bony erosions (punched out lesions with overhanging edges) on plain radiograph or (7) tophi. Acute attacks most o ten a ect the rst metatarsophalangeal joint (up to 50% o rst attacks). The tarsal joints, ankles, knees, elbows, and interphalangeal (IP) joints are also commonly a ected. In elderly patients with osteoarthritis (OA), Heberden and Bouchard nodes (seen in hand OA) are potential targets or in ammation, and red, swollen proximal and distal IP joints may be the rst mani estation o gout. Episodes o acute gouty arthritis requently come on rapidly at night or in the early morning with dramatic pain and swelling. The joint becomes warm, red, and tender, o ten mimicking cellulitis. Without treatment, most acute attacks resolve in 2 to 14 days.

PRACTICE POINT Figure 247 1 Tophaceous gout causing an erosive arthropathy. Note the large tophi (stars) and “rat-bite” erosions with overhanging edges (arrows).

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In a postoperative or postdiuresis patient with an acute in ammatory arthropathy, with or without ever, consider gout or another crystal arthropathy in the di erential diagnosis. 2025

While acute gout attacks can o ten be managed in the outpatient setting, patients may need to be admitted to the hospital to acilitate workup or to rapidly and de nitively rule out the possibility o in ection. Patients with severe disability rom their acute attack and inadequate home support may need to be admitted until they are able to ambulate or otherwise unction. O ten, patients at risk may develop acute gouty attacks while hospitalized or other problems. In the hospital setting, attacks may be precipitated by metabolic acidosis, asting, diuretics, or disruptions in volume status or renal unction that may cause acute swings (both elevations and depressions) in serum urate levels. Discontinuation o urate lowering therapy in hospitalized gout patients is a common error that can lead to acute serum urate changes that provoke gouty attacks; this practice is not recommended according to the American College o Rheumatology (ACR) 2012 treatment guidelines. Gout ares occurring during hospitalization or other causes are generally avoidable, and increase the length o stay by approximately 3 days.

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■ HOSPITAL ADMISSION

■ TREATMENT OF ACUTE GOUT Colchicine is e ective in the acute setting, and, i initiated su ciently early, may abrogate an acute attack. It is typically less e ective a ter the attack is established (≥36 hours). The traditional dosing o colchicine or acute attacks (0.6 mg by mouth every 1-2 hours until onset o relie or a maximum o 6 mg) requently led to undesirable side e ects. A more limited regimen—colchicine 1.2 mg, ollowed by 0.6 mg 1 hour later—is equally e ective, with toxicity similar to placebo. It has now been adopted as standard o care. Patients with renal insuf ciency may receive this regimen, but should subsequently discontinue any use o low-dose daily colchicine or several weeks; patients without renal disease may continue their prophylaxis unabated.

PRACTICE POINT

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Treatments or acute gout, such as NSAIDs, glucocorticoids and particularly colchicine, work best when administered within hours o the onset o the attack.

For many patients, NSAIDs are pre erred agents or acute gout. Indomethacin is the traditional choice at 50 to 75 mg initially, then 50 mg every 6 hours, not exceeding 200 mg in a 24-hour period. However, clinical studies have shown that many other NSAIDs, including COX-2 selective agents, are as e ective as indomethacin when used at their maximum doses and may be better tolerated. NSAIDs have the advantage o both analgesic and anti-in ammatory e ects, but may be relatively contraindicated in patients with gastritis, renal insuf ciency, hypertension, and heart ailure. In order to maximize response time while minimizing side e ects, a combination o more than one class o medications, such as NSAID plus colchicine, is sometimes used in treating acute attacks. Glucocorticoids are potent anti-in ammatory agents that can be highly e ective at abrogating acute gouty attacks. Intraarticular glucocorticoids may be particularly use ul in treating acute gout in a single joint or bursa when systemic glucocorticoid use is undesirable. Care must be taken to establish the diagnosis and to rule out in ection prior to injecting glucocorticoids directly into the joint. As a practical matter, this o ten means per orming joint aspiration and injection as separate procedures, which may un ortunately add to the patient’s discom ort. Oral and intravenous glucocorticoids are both very e ective, especially in patients with polyarticular attacks, and may be the agents o choice in patients with contraindications to colchicine and NSAIDs, such as renal insuf ciency. ACR guidelines 2026

recommend a starting dose o approximately 0.5 mg/kg/d o oral prednisone. Although treatment periods with oral steroids are typically brie (about a week), relative contraindications such as diabetes, hypertension, and heart ailure must be considered. A single intramuscular injection o depot adrenocorticotropic hormone, or ACTH gel (25-80 IU, repeated 24-72 hours later i needed) can also terminate attacks e ectively and may be particularly use ul in patients who cannot take oral medication. In addition to stimulating the adrenal cortex to produce corticosteroids, ACTH reduces the acute in ammatory response by activating melanocortin receptor-3. Follow-up treatment using low-dose (one to two times daily) colchicine is typically recommended to prevent rebound attacks as the ACTH wears o . However, ACTH gel is currently not Food and Drug Administration (FDA) approved or use in gout, and its high cost in the United States limits its use. Given the role o IL-1β in acute gouty in ammation, several studies have addressed the use o anti-IL-1β biological therapy in acute gout ares. Both anakinra, an IL-1β receptor antagonist, and canakinumab, an anti-IL-1β antibody, have shown ef cacy. Although expensive and o -label, these agents may be considered when established therapies have ailed and/or are contraindicated.

■ CHRONIC MANAGEMENT OF GOUT The goal o chronic gout management is to prevent acute attacks and to decrease the total body urate burden, including both visible tophi and occult deposits. This is achieved by lowering serum urate to less than 6 mg/dL, and requires a multipronged approach. Li estyle changes such as weight loss, avoidance o ructose-rich oods and high-purine oods such as organ meats and shell sh, and eliminating or reducing alcohol consumption should be the rst step, with the addition o one or more urate-lowering agents being necessary or most patients with chronic gout. Medication review may identi y agents that are contributing to hyperuricemia. For example, thiazides and loop diuretics reduce uric acid excretion and raise serum urate. There ore, these should be used at the lowest e ective dose, or stopped i appropriate alternatives are available. Both losartan ( or hypertension) and eno brate ( or hyperlipidemia) have uricosuric properties and may be use ul options or treatment o these conditions in patients who also have gout. Current ACR guidelines address the management o gout patients, including the initiation o urate-lowering therapy. Uratelowering therapy should be started on any gout patient with 2 or more attacks in a 12-month period. Patients with tophi should also undergo urate lowering, as should patients with stage 2 or worse chronic kidney disease or a history o urolithiasis, even a ter only a single attack. Urate-lowering agents commonly used to treat chronic gout include inhibitors o xanthine oxidase (allopurinol and ebuxostat) and uricosuric agents (probenecid, sul npyrazone, and benzbromarone). Long considered a rst-line agent or chronic gout management, allopurinol is a purine analog o hypoxanthine. Along with its active metabolite oxypurinol, allopurinol competitively inhibits xanthine oxidase, decreasing urate production and serum uric acid levels. Appropriate allopurinol use requires dose titration to achieve a prespeci ed serum urate target, most commonly 7.5 mg to ≤30 mg/d, and high dose as >30 mg to ≤100 mg/d. Pulse therapy is de ned as ≥250 mg/d, usually or one or a ew days, although practically speaking; most physicians use 500 to 1000 mg o intravenous methylprednisolone equivalent or pulse therapy. Tapers are highly variable in dosing and duration; alternate-day dosing is an option or tapering steroids. During tapering, patients should be closely monitored or symptoms o an SLE are, as well as or signs o adrenal insuf ciency. Hydroxychloroquine reduces the requency o SLE ares and improves survival. It has avorable e ects on lipids, blood glucose, and may reduce the risk o blood clots in individuals with SLE and antiphospholipid antibodies. I dosed at less than 6.5 mg/kg daily o ideal body weight, retinal toxicity is a rare adverse e ect. The usual dose o hydroxychloroquine is 400 mg once daily or divided twice daily. Gastrointestinal side e ects are uncommon, but may be reduced by taking the medication a ter a meal. As it is not immunosuppressive, hydroxychloroquine can be continued during acute in ection. Hydroxychloroquine has not been shown to impair healing and can be continued perioperatively. It is also one o the medications recommended or the management o lupus during pregnancy. The management o allergic reactions to hydroxychloroquine is complicated by the medication hal -li e o several weeks. Belimumab is a human monoclonal antibody that binds to and inhibits soluble human B lymphocyte stimulator (BlyS). Belimumab is particularly e ective in patients with SLE who have higher disease activity, are taking corticosteroids, and have elevated anti-DNA antibodies and low complement levels. Clinical responses to belimumab have been reported to have sustained or up to 7 years. In an open-label extension trial, severe ares declined rom 17% with belimumab in the rst year to 2% to 9% during years 2 to 7. Anti-dsDNA antibodies declined 40% to 60% rom baseline over 2 to 7 years. Corticosteroid use also declined by 25% at year 2 and by 55% at year 7, and overall adverse event rates stabilized or decreased during the 7 years o treatment. These results suggest that belimumab is well tolerated and can control disease or long periods o time. This agent will likely not have a signi cant role in the setting o the hospitalized patient with an acute are o SLE. Rituximab ailed to meet clinical endpoints when tested in randomized clinical trials or both generalized SLE and lupus nephritis (the EXPLORER and LUNAR trials, respectively), although concerns have been raised about the very strict endpoints used in both o these trials, as well as the exclusion o patients with severe disease who may be more representative o those more likely to receive rituximab in clinical practice. Based on previously

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■ ACUTE DISEASE FLARES

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hemorrhagic, especially in the setting o hypertension or thrombocytopenia. Individuals with SLE with acute weakness in one or more extremities should be admitted or urther evaluation and management; diagnostic considerations include stroke, transverse myelitis, mononeuritis multiplex, mixed sensorimotor polyneuropathies, and cranial and peripheral neuropathies.

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epidermal necrolysis (TEN), or Stevens-Johnson syndrome. TEN-like acute cutaneous lupus is occasionally seen in SLE, and severe mucous membrane involvement is common. Skin disease may also result rom the treatment o SLE. Hydroxychloroquine has been associated with acute generalized exanthematous pustulosis (AGEP), a cutaneous hypersensitivity reaction that presents as a desquamating rash on the ace and chest. Patients with cytopenias may need admission or evaluation and management. Individuals with SLE and the new onset o less than 50,000 platelets/mm 3 should be considered or inpatient evaluation and management, especially i bleeding is present. Likewise, patients with hemolytic anemia may require admission or management. Antibody-mediated clotting actor inhibitors, such as acquired actor VIII inhibitor, have been described in patients with SLE and can be li e-threatening. Pericarditis is the most common cardiac mani estation o SLE. Though rare, cardiac tamponade can occur; the presence o dyspnea with a large pericardial e usion, pulsus paradoxus on examination, or tamponade physiology on echocardiogram necessitates admission. Large pleural e usions associated with dyspnea may require admission or diagnostic and therapeutic thoracentesis. Empyema must be ruled out in any large pleural e usion in a patient with SLE. Individuals with SLE may present with accelerated hypertension (systolic blood pressure [BP] ≥ 180 mm Hg or diastolic BP ≥ 110 mm Hg). Hypertensive emergency and hypertensive urgency have the same de nition in individuals with SLE as in other patients, and considerations or admission are similar. In hypertensive patients with SLE, it may be dif cult to determine whether additional ndings, such as con usion and microangiopathic hemolytic anemia, are the product o hypertensive crisis or are directly related to lupus disease activity. Glomerulonephritis must always be excluded in any patient with SLE with severe hypertension. Acute dyspnea or a new oxygen requirement in an individual with SLE warrants admission. Cardiac causes o acute dyspnea in SLE include acute coronary syndromes, pericardial or pleural e usion, valvular heart disease related to SLE, and congestive heart ailure. Libman-Sacks endocarditis most commonly involves the tricuspid and mitral valves, and is associated with antiphospholipid antibodies. New peripheral emboli may require hospital admission or evaluation and initiation o anticoagulation. SLE may cause myocarditis, cardiomyopathy, or congestive heart ailure. Pulmonary causes o dyspnea in SLE include pleural e usions, interstitial lung disease, pneumonia, pulmonary embolism, and pulmonary hemorrhage. Additionally, acute coronary syndromes or myocardial in arction must always be considered in any patient with SLE who has dyspnea. Lupus itsel is a risk actor or cardiovascular disease; myocardial in arctions in the absence o traditional risk actors can occur even in very young women with SLE. ECG ndings suggestive o cardiac ischemia or the presence o elevated serum biomarkers are absolute indicators or admission in this population. Worsening hypertension and peripheral edema associated with proteinuria can be signs o lupus nephritis. Admission is indicated in suspected lupus nephritis i hemodialysis may be necessary to treat volume overload or electrolyte disturbances, to expedite renal biopsy, or to start pulse treatment with methylprednisolone or 3 to 5 days a ter renal biopsy has been per ormed. Additionally, individuals ailing outpatient management o known lupus nephritis (eg worsening microscopic hematuria, worsening proteinuria, increasing creatinine, inability to control blood pressure) may also be admitted or pulse therapy with methylprednisolone as de ned below as well as aggressive antihypertensive therapy. A patient with SLE with a rst seizure should be admitted or urther evaluation. Individuals with SLE have a higher incidence o cerebrovascular disease and can present with stroke at a young age. Stroke in SLE may result rom thromboembolism or can be

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P A R T V I C l i n i c a l C o n d i t i g

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reported trends toward improvement, additional trials are ongoing (RING, RITUXILUP) to urther address the potential role o rituximab in lupus nephritis. IVIG has a limited role in patients with SLE. However, a recent meta-analysis and systematic review demonstrated that IVIG reduces disease activity scores and can increase serum complement levels. IVIG is also ef cacious in the management o autoimmune hemolytic anemia and thrombocytopenia. There are insuf cient data to determine its role in other clinical outcome measures, including renal unction. Speci c discussion o the use o IVIG in individual clinical circumstances, including heart block, is addressed in individual sections below. Several promising agents or the treatment o SLE are currently in development. Most are biologic therapies targeting speci c immune unctions implicated in lupus disease activity. Epratuzumab (anti-CD22 antibody) is currently in late-phase clinical trials, while the anti-IFNα agent, rontalizumab, is in early phase clinical trials.

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■ NEPHRITIS Although there are several published randomized clinical trials or the treatment o lupus nephritis, there is no consensus on optimal treatment, and a knowledgeable rheumatologist or nephrologist should be consulted to recommend appropriate therapy. Class II (mesangial) lupus nephritis generally improves with corticosteroids alone. Proli erative glomerulonephritis (class III or IV) merits aggressive therapy to prevent progression to end-stage renal disease. Many patients have simultaneous pathologic and clinical eatures o proli erative and membranous (class V) glomerulonephritis, although membranous (Class V) can also occur by itsel . There are three major published regimens or induction treatment o class III, IV, and V lupus nephritis. The rst protocol (NIH protocol) is comprised o 6 monthly pulses o intravenous cyclophosphamide (500-750 mg/m 2), with oral prednisone starting at 1 mg/kg daily or 8 weeks and weaned over 12 months. This regimen carries risks o serious in ection, in ertility and malignancy. In a search or equally e ective and less toxic treatments, two other regimens have emerged. In the Euro-lupus protocol, 3 daily pulses o 750 mg methylprednisolone are initially administered, ollowed by cyclophosphamide 500 mg intravenously every 2 weeks or 6 doses. Oral azathioprine (AZA) is then used or maintenance therapy. Prednisone is dosed similarly to the NIH protocol. This regimen was shown to be non-in erior to the NIH protocol in a European trial, although the study was composed o mostly Caucasian participants. The third induction regimen uses oral MMF 1500 mg twice daily with oral corticosteroids, starting at 1 mg/kg and tapered over approximately 6 months. In a comparison trial o oral MMF and monthly intravenous cyclophosphamide using the NIH protocol or 6 months (both with the same steroid regimen), oral MMF was shown to be non-in erior to monthly intravenous cyclophosphamide. Subgroup analysis o this trial suggested that oral MMF may provide improved renal survival in non-Caucasian and non-Asian patients. An additional advantage o MMF is preserved ertility compared to cyclophosphamide. A ter induction therapy, maintenance therapy is usually with MMF, which has been shown to be superior to AZA. Calcineurin inhibitors are also showing promise or management o active lupus nephritis. In a Chinese population, tacrolimus was nonin erior to MMF or induction purposes, though a ter 5 years o ollow-up, a nonsigni cant trend o a higher incidence o renal ares and renal unction decline was observed with the tacrolimus regimen. The ongoing RITUXILUP trial is currently evaluating whether rituximab and MMF, without the addition o oral steroids, has an improved response and prolonged steroid-sparing e ect in the treatment o new lupus nephritis. The 2012 ACR guidelines or management o lupus nephritis suggest that, or pure Class V LN with nephrotic range proteinuria,

patients should be started on prednisone 0.5 mg/kg/d, in combination with mycophenolate mo etil (2-3 g total daily dose). A recently published clinical trial demonstrated 1-year clinical remission rates o 83% with daily cyclosporine and 60% with intravenous cyclophosphamide every other month or six doses. Both regimens were accompanied by alternate day prednisone starting at 40 mg/m 2 or 8 weeks, then tapered over a year, as well as angiotensin-converting enzyme (ACE) inhibitors and daily oral statins. Another recently reported pooled analysis o two clinical trials ound no di erence in remission rates between intravenous cyclophosphamide and mycophenolate mo etil or pure class V nephritis. A subgroup analysis o the previously mentioned randomized control trial evaluating tacrolimus (0.06-0.1mg/kg/d) versus MMF (2-3 g/d) demonstrated that, or patients with pure class V membranous lupus nephritis, tacrolimus had a greater e ect on reducing the urine protein to creatinine ratio, as well as a trend toward an increased likelihood o a complete renal response as de ned by the ACR SLE renal response criteria. All classes o nephritis are associated with a signi cantly increased risk o cardiovascular disease; up to hal o patients with nephritis eventually die rom cardiovascular or cerebrovascular disease. The risk o thrombotic disease related to antiphospholipid antibodies and nephrotic syndrome is around 20% in this patient population. ACE inhibition is considered essential adjunctive treatment to reduce proteinuria. Combination antihypertensive therapy with a target blood pressure o 120/80 is recommended. Statin therapy should be considered, with a target LDL o less than 100.

■ SEROSITIS The greatest risk o pericardial tamponade occurs with e usions that are rapidly accumulating. Case series o large pericardial e usions in lupus suggest that oral prednisone 0.5 to 1 mg/kg daily with immediate placement o a pericardial drainage catheter results in resolution in about hal o the patients, with the other hal requiring pericardial window. I a large pericardial e usion is accompanied by other severe mani estations o SLE, or i a large e usion has accumulated rapidly, one should strongly consider a daily pulse o methylprednisolone 1000 mg or 3 days at the beginning o treatment. Colchicine 0.6 mg twice daily is use ul or the management o small to moderate symptomatic pericardial e usions. NSAIDs are another alternative in patients with normal renal unction. There are minimal data to guide treatment o symptomatic pleural e usions in SLE. Thoracentesis should be per ormed to rule out in ection, and patients should be treated with oral prednisone 0.5 to 1 mg/kg daily. With recurrent pleural or pericardial e usions, steroid-sparing agents such as AZA, MMF, cyclosporine, or methotrexate (MTX) should be considered. Other pulmonary mani estations such as interstitial lung disease and shrinking lung syndrome are less common, and scant data are available to guide treatment. Considerations include immunosuppressive regimens listed above; the choice o therapy is also based on individual patient presentations and comorbidities.

■ CUTANEOUS LUPUS The most likely reasons or hospital admission in a patient with cutaneous mani estations o lupus are bullous lupus or cutaneous vasculitis with ulcerations. Bullous lupus improves rapidly with dapsone, but the diagnosis must be certain, as TEN and StevensJohnson syndrome do not similarly respond to dapsone. Severe mucocutaneous involvement rom SLE may necessitate intravenous corticosteroids and adequate hydration. When intravenous steroids are used or cutaneous lupus, they are generally dosed at or above the equivalent o prednisone 1 mg/kg/d. Cutaneous vasculitis rom SLE should be con rmed by skin biopsy i possible, then treated initially with daily oral prednisone 1 mg/kg. A second immunosuppressive agent, usually AZA (2-3 mg/kg daily), MTX (15-25 mg orally

■ NEUROPSYCHIATRIC DISEASE Patients with lupus presenting with new seizures, or which other causes have been excluded, should be treated with anticonvulsants and three to ve daily pulses o 1000 mg methylprednisolone, ollowed by a prednisone taper beginning at 1 mg/kg/d. A steroid-sparing oral immunosuppressive is o ten added. For most mani estations o NPSLE, intravenous cyclophosphamide is given as steroid-sparing therapy, but the optimal duration o treatment has not been determined by randomized controlled trials. Many case series describe the use o MMF and AZA or NPSLE as well. IVIG is requently used or NPSLE, especially when the peripheral nervous system is involved. We suggest the 2010 EULAR recommendations or the management o SLE with neuropsychiatric mani estations as a use ul resource when contemplating treatment.

■ MUSCULOSKELETAL In ammatory arthritis ares can be treated with NSAIDs. I a patient has severe unctional limitation or requires hospitalization due to in ammatory arthritis, prednisone can be started at 0.5 mg/kg or less, and tapered over 1 to 3 weeks. Alternatively, patients can be given up to 120 mg o depot intramuscular steroid, such as triamcinolone, an approach that decreases the cumulative li etime steroid dose. In ammatory arthritis re ractory to hydroxychloroquine is usually treated with MTX or AZA. SLE-associated in ammatory myopathy is treated with prednisone 1 mg/kg daily or at least a month while starting a steroidsparing agent such as MTX, MMF or AZA. IVIG is used in severe cases.

■ HEART BLOCK IVIG is currently being studied as a salvage treatment or pregnant women with anti-Ro (SSA) and/or anti-La (SSB) antibodies and a etus

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Morbidity and mortality rom lupus can occur both rom the disease itsel , and rom complications o treatment. Treatment-related complications in the hospital rom high-dose glucocorticoids include hyperglycemia, hypertension, and psychiatric mani estations, such as mania, delirium, and agitation. Many patients require sleep aids or anxiolytics while taking glucocorticoids. In patients with severe neuropsychiatric lupus, it can be dif cult to di erentiate the e ects o the disease rom those o its treatment; rheumatology, neurology, and psychiatric consultation may be help ul in this regard. Cyclophosphamide can cause hemorrhagic cystitis. This risk may be reduced by administering mesna with IV cyclophosphamide, as well as maintaining adequate urine output through intravenous hydration. A white blood cell count nadir should be checked 10 to 14 days a ter high-dose intravenous cyclophosphamide. Patients on cyclophosphamide are at an increased risk o in ection; prophylaxis against Pneumocystis jirovecii, usually with trimethoprimsul amethoxazole, is warranted. Cyclophosphamide is associated with an age- and dose-dependent risk o premature ovarian ailure in women, and in ertility in both men and women. Time permitting, egg storing or sperm banking may be considered, although initiation o CYC should not be delayed in situations o medical necessity. Gonadotropin-releasing hormone agonists such as leuprolide have a role in gonadal protection in women, and intramuscular testosterone can be considered in men. Up to 25% o deaths in SLE are attributable to in ections. These may present in atypical ashion, as high-dose corticosteroids minimize ever and other symptoms. In ection is most o ten due to common pathogens, such as Escherichia coli, Staphylococcal aureus, and Streptococcus pneumoniae, although patients with lupus are also at substantial risk o tuberculosis. Higher SLE disease activity and more immunosuppressive treatment are correlated with a higher in ection risk; there is some evidence that antimalarials may protect against in ection. Progressive multi ocal leukoencephalopathy (PML) has been reported in patients with SLE treated with rituximab, mycophenolate mo etil, cyclophosphamide, and other immunosuppressive regimens including corticosteroids alone. PML should be considered in patients with SLE and neurologic symptoms including altered mental status, motor de cits, ataxia, or visual disturbances such as diplopia. Corticosteroids impair wound healing and increase the risk o in ection in patients with SLE undergoing surgery. Methotrexate continued through the perioperative period has not been associated with an increase in post-operative in ections or a delay in wound healing in patients with other autoimmune diseases. However, some groups have suggested holding MMF and AZA or 10 to 14 days both be ore and a ter surgery to diminish the risk o perioperative in ection, though this has not been speci cally studied by randomized trials. Avascular necrosis is another untoward complication o glucocorticoid therapy. The hips, shoulders, and knees are most commonly a ected. O course, the best way to prevent complications o glucocorticoid therapy is to minimize the dose and duration o treatment.

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Depending on the severity o hemolytic anemia, high-dose intravenous steroids may be warranted, between 500 and 1000 mg o methylprednisolone daily or 1 to 5 days. Once the anemia stabilizes, patients are transitioned to oral prednisone 1 mg/kg daily, which is tapered over a ew months. Oral immunosuppressives should be considered in recurrent or re ractory cases. Thrombocytopenia with hemorrhagic complications is treated similarly, and intravenous immunoglobulin (IVIG) is o ten used when hemorrhagic complications occur. Dosing regimens or IVIG may include 1 g/kg daily or 1 to 2 days, or 400 mg/kg/d or 5 days. Oral immunosuppressives are started in recurrent or re ractory cases. TTP in patients with lupus is treated as in patients without lupus: daily plasma exchange and high-dose intravenous steroids until the platelet count reaches a sa e level and measures o hemolysis activity normalize. For adjunctive therapy in re ractory cases, cyclophosphamide may be given to patients with lupus (vincristine is more commonly administered outside the setting o SLE). Although rituximab showed no bene t in a randomized clinical trial or treatment o active SLE, a small case series suggested potential bene t o rituximab or SLE-associated TTP. Rituximab is approved or treatment o ITP and is o ten success ully used to treat patients with SLE, thrombocytopenia, and bleeding. Although plasma exchange has been used in nearly every mani estation o SLE, it has thus ar only been shown to be bene cial or TTP, catastrophic antiphospholipid antibody syndrome (CAPS), and neuromyelitis optica (optic neuritis with segmental transverse myelitis and anti-aquaporin-4 antibody positivity).

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with cardiac conduction abnormalities, sometimes in combination with plasma exchange and corticosteroids. Clinical trial results are pending or this indication. We would recommend this treatment be undertaken only in collaboration with a rheumatologist.

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weekly), or MMF (up to 1500 mg twice daily) is also given. As with other disease mani estations, patients with cutaneous lupus should be treated with hydroxychloroquine unless there is a known allergy.

DISCHARGE CHECKLIST • Is the lupus mani estation leading to admission stable? Patients

with pericardial e usions should not be discharged until the risk or pericardial tamponade has passed. Discharge can be considered or thrombocytopenic patients once the platelet count has 2043

TABLE 248-7 Therapy Monitoring for Drugs Commonly Used to Treat Systemic Lupus Erythematosus Agent Hydroxychloroquine

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stabilized and bleeding has ceased. In TTP, a response to therapy is indicated by a platelet count stabilized over 150,000/mm 3. • Have cardiac risk actors, such as hypertension and hyperlipidemia, been addressed? Patients with corticosteroid-induced diabetes should be under good glycemic control at discharge and be given education and instructions in the case o high or low readings prior to discharge. As there is a high risk o cardiovascular comorbidity in patients with SLE, we recommend the ollowing similar guidelines as or diabetes mellitus, with a blood pressure target o less than 140/90 mm Hg and goal LDL cholesterol o less than 100 mg/dL. Behavioral issues such as obesity, diet, exercise, and smoking cessation should also be addressed. • Has monitoring been arranged or toxicity o immunosuppressive medications? Recommended laboratory studies and their requency are included in Table 248-7.

NSAIDs Glucocorticoids

Azathioprine

Mycophenolate Mo etil Methotrexate

Cyclophosphamide

Testing Dilated unduscopic exam, visual ield testing, and either spectral domain OCT (SD-OCT), multi ocal electroretinogram (m ERG), or undus auto luorescence CBC, Cr Bone mineral density Glucose Fasting lipid panel CBC, Cr, AST

Skin cancer screening Pregnancy test CBC Chest X-ray Hepatitis B, C Pregnancy test CBC, Cr, AST, albumin CBC and di erential

Urinalysis Creatinine, electrolytes

Hepatic unction panel Pregnancy test

Frequency Recommendations vary, generally every 12 mo

Every 12 mo Every 1-2 y Yearly Yearly Every 1-2 wk a ter dosage change, then every 4-8 wk Yearly At drug initiation Every 4-8 wk At drug initiation At drug initiation At drug initiation Every 4-8 wk Oral: 2 wk a ter initiation or dose change, then every 4 wk once stable. IV: check nadir 10-14 d a ter dose Monthly Oral: 2 wk a ter initiation or dose change, then every 4 wk once stable. IV: concurrent with CBC Monthly At drug initiation

AST, aspartate aminotrans erase; CBC, complete blood count; Cr, creatinine; OCT, optical coherence tomography.

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• For patients being discharged on azathioprine, have levels o thio-

purine methyltrans erase (TPMT) been checked? Levels o TPMT can predict the likelihood o leukopenia or other adverse e ects rom azathioprine treatment. I TPMT testing is pending, a patient newly started on azathioprine should have a complete blood count (CBC) every 2 weeks as the dosage is advanced. • Has appropriate ollow-up with a rheumatologist been scheduled prior to discharge? • I cyclophosphamide has been administered, has a ollow-up blood count between days 10 and 14 been scheduled? • I prednisone >5 mg daily is prescribed, has glucocorticoid toxicity been minimized by checking serum vitamin D, starting calcium 1200 mg daily, and vitamin D 800 to 1000 IU daily? I warranted, has a bisphosphonate or teriparatide been initiated? Patients should have both a risk assessment or glucocorticoid-induced osteoporosis (GIOP) and be started on treatment i indicated, as per the algorithm in Figure 248-7. Patients should be counseled to participate in weight-bearing exercise, to avoid smoking, and to modi y other possible osteoporosis risk actors. Serum 25-hydroxyvitamin D should be measured, as studies have shown

Calc ium and vitamin D Ens ure a de qua te ca lcium inta ke (1200 mg/d) Vita min D s upple me nta tion (monitor leve ls of 25-OH vita min D in pa tie nts with S LE a s glucocorticoids ca n inte rfe re with vita min D a bs orption)

Life s tyle c o uns e ling We ight-be a ring a ctivitie s S moking ce s s a tion Avoid drinking ≥ 3 a lcoholic drinks /d

Ris k as s e s s me nt As s e s s fa ll ris k by que s tioning a bout prior fa lls a nd obs e rving pa tie nt’s ga it Me a s ure ba s e line he ight Ba s e line dua l x-ray a bs orptiome try (DXA) Utilize FRAX tool Cons ide r ima ging of s pine to de te ct a symptoma tic fra cture s

No prio r frag ility frac ture Ina de qua te evide nce Cons ide r individua l s itua tion

Prio r frag ility frac ture Us e bis phos phona te if pla nne d glucocorticoid tre a tme nt dura tion of ≥ 3 mo. Dos e cutoff is ≥ 7.5 mg pre dnis one da ily for wome n of childbe a ring pote ntia l a nd ≥ 5 mg for me n or wome n not of childbe a ring pote ntia l

Figure 248 7 Summary of recommendations for the prevention of glucocorticoid-induced osteoporosis in premenopausal women and men under age 50. These recommendations place a large focus on assessing fracture risk. The American College of Rheumatology task force concluded there were inadequate data to make recommendations for individuals who have not experienced a prior fragility fracture in these age groups. (Data rom Grossman JR, Gordon R, Ranganath VK, et al. American College o Rheumatology 2010 recommendations or the prevention and treatment o glucocorticoid-induced osteoporosis. Arthritis Care Res. 2010;62:1515-1526.)

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Mok CC, Ying KY, Yim CW, et al. Tacrolimus versus mycophenolate mo etil or induction therapy o lupus nephritis: a randomised controlled trial and long-term ollow-up. Ann Rheum Dis. 2016;75:30-36.

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Hahn BH, McMahon MA, Wilkinson A, et al. American College o Rheumatology guidelines or screening, case de nition, treatment, and management o lupus nephritis. Arthritis Care Res. 2012;64:797-808.

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Hahn BH. Belimumab or systemic lupus erythematosus. N Engl J Med. 2013;368:1528-1535.

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Choi BY, Yoon MJ, Shin K, et al. Characteristics o pleural e usions in systemic lupus erythematosus: di erential diagnosis o lupus pleuritis. Lupus. 2015;24:321-326

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Bertsias G, Ioannidis JP, Boletis J, et al. EULAR recommendations or the management o systemic lupus erythematosus. Ann Rheum Dis. 2008;67:195-205.

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Bertsias G, Ioannidis JP, Aringer M, et al. EULAR recommendations or the management o systemic lupus erythematosus with neuropsychiatric mani estations: report o a task orce o the EULAR standing committee or clinical a airs. Ann Rheum Dis. 2010;69:2074-2082.

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that vitamin D levels are consistently low in patients with SLE. Additionally, vitamin D has immunomodulatory properties, and evidence suggests an inverse relationship between vitamin D levels and lupus disease activity. Are outpatient physical and occupational therapy appropriate? Have discharge planners ensured that treatment plans are likely to be continued a ter discharge? Un ortunately, severe SLE disproportionately a ects underserved populations, and many patients are uninsured or underinsured. Patients may need help with arranging transportation to and rom ollow-up appointments. In-home therapy and nursing aides should be considered i indicated. Has the patient received counseling to avoid prolonged sun exposure and to wear sunscreen? Sun exposure can cause not only a photosensitive rash, but also lead to increased SLE activity systemically; as a result, patients with SLE should both avoid the sun and use sunscreen. Have new medications been assessed or drug interactions? I teratogenic medications are being prescribed to a women o childbearing age, is there a plan or contraception? Several immunosuppressive agents, including methotrexate, MMF, cyclophosphamide, and le unomide, are potent teratogens. Has the patient received pneumococcal and annual in uenza vaccination? Current immunization guidelines advise that adult patients 19 years and older with an immunocompromising condition (who have not previously received pneumonia vaccination) receive one dose o PCV-13 ollowed by a dose o PPSV-23 at least 8 weeks later. Live vaccines should be avoided in individuals treated with more than 10 mg o daily prednisone or its equivalent. Have outpatient in usions been scheduled or patients who are to receive them, and has the insurance approval process been started? In patients receiving immunosuppressive medications, has prophylaxis or pneumocystis pneumonia (PJP) been considered? Expert opinion suggests trimethoprim-sul amethoxazole one doublestrength tablet three times weekly or one single-strength tablet daily or patients continued on prednisone ≥20 mg daily or 1 month or longer in combination with a second immunosuppressive drug.

Mosca M, Tani C, Aringer M, et al. European League Against Rheumatism recommendations or monitoring patients with systemic lupus erythematosus in clinical practice and in observational studies. Ann Rheum Dis. 2010;69:1269-1274. Ortega LM, Schultz DR, Lenz O, Pardo V, Contreras GN. Lupus nephritis: pathologic eatures, epidemiology and a guide to therapeutic decisions. Lupus. 2010;19:557-574. Ruiz-Irastorza G, Cuadrado M, Ruiz-Arruza I, et al. Evidence-based recommendations or the prevention and long-term management o thrombosis in antiphospholipid antibody-positive patients. Lupus. 2011;20:206-218. Tsokos G. Systemic lupus erythematosus. N Engl J Med. 2011;365:2110-2121.

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249

CHAP TER

Rheumatoid Arthritis and Other In lammatory Arthritides Victoria D. Lackey, MD Lisa Criscione -Schreiber, MD Marcy B. Bolster, MD

Key Clinical Questions 1

Does this patient have rheumatoid arthritis or another in lammatory arthritis?

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What are the extra-articular mani estations o rheumatoid disease?

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Is a rheumatic condition responsible or this patient’s hospitalization?

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Is this hospitalization due to medication toxicity?

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How should the patient’s disease-modi ying antirheumatic drugs be managed during the hospitalization, including perioperatively?

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What tests and studies are use ul to evaluate this patient’s presentation?

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What treatments are indicated?

EPIDEMIOLOGY Rheumatoid arthritis (RA) a ects 1% o the population worldwide, with women being more commonly a ected. Within the past two decades, prior to routine early use o disease-modi ying antirheumatic drugs (DMARDs), patients were requently admitted to the hospital or active arthritis treatment. Today, most RA treatment occurs in the outpatient setting. However, RA is a systemic disease with numerous potential extra-articular mani estations, including cardiovascular disease. A hospitalist must be alert to these mani estations, as they may lead to hospitalization.

PRACTICE POINT

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Early, aggressive DMARD use is a cornerstone o current RA management. The duration o rheumatoid arthritis prior to DMARD therapy is one o the most robust predictors o disease outcome. Longer delays in initiation o DMARDs are associated with greater long-term unctional impairment. DMARDs may also attenuate the risk o cardiovascular disease, which is increased in RA.

Most other common in ammatory arthritides all into the category o seronegative spondyloarthropathies, which a ect up to 2% o individuals with an equal male-to- emale ratio. The seronegative spondyloarthropathies include psoriatic arthritis (PsA) (population prevalence 0.3%-1.0%), ankylosing spondylitis (AS) (prevalence 0.1%-6.0%, depending on the population studied), in ammatorybowel-disease-associated arthritis, reactive arthritis, and undi erentiated spondyloarthropathy. These illnesses are seronegative or rheumatoid actor (RF), and are associated with the presence o human leukocyte antigen (HLA)-B27. The presence o HLA-B27 varies by ancestry. In general, up to 15% o the population is HLA-B27 positive, although only about 10% o these individuals develop a spondyloarthropathy. However, among individuals with spondyloarthropathies, up to 90% are HLA-B27 positive. Spondyloarthritis is characterized by axial arthritis, with a predilection or the sacroiliac joints, oligoarthritis, especially o the lower extremities, and enthesitis, or in ammation o ligaments and tendons at their attachments to bone. In ammatory arthritis may be just one mani estation o a systemic disease that may include psoriasis and psoriasi orm skin lesions, oral and genital in ammation, in ammatory bowel disease, and in ammatory eye disease, such as uveitis or scleritis. PATHOPHYSIOLOGY Rheumatoid arthritis is thought to result when an environmental actor triggers an aberrant immune response in a genetically susceptible host. Several genes are associated with susceptibility to the development o RA. Most signi cantly, RA is associated with HLA-DRB1. A short amino acid sequence within this gene, known as the shared epitope, is associated with increased risk o severe RA and development o anticitrullinated-peptide antibodies. Autoantibodies against citrullinated peptides appear to be almost 90% speci c or rheumatoid arthritis, although less sensitive than the RF assay. Identi cation o these autoantibodies is now part o routine diagnostic testing or RA via the anticyclic-citrullinated peptide (antiCCP) autoantibody assay. An immune reaction against citrullinated

Figure 249 1 Progressive destruction o a metacarpophalangeal joint by rheumatoid arthritis. Shown are sequential radiographs o the same second-metacarpophalangeal joint. (A) The joint is normal 1 year prior to the development o rheumatoid arthritis. (B) Six months a ter the onset o rheumatoid arthritis, there is a bony-erosion adjacent to the joint and joint space narrowing. (C) A ter 3 years o disease, di use loss o articular cartilage has led to marked joint space narrowing. (Reproduced, with permission, rom Imboden J, Hellmann DB, Stone JH. Current Rheumatology Diagnosis &Treatment, 2nd ed. New York, NY: McGraw-Hill, 2007. Fig. 15-3.)

C H A P T 2 4 9 R h e u m a t o i d A r t h r i t i s a n d O t h e r I n l a m m a t o r y A r t h r i t i

Even with advances in diagnostic testing and imaging, in ammatory arthritides are diagnosed clinically, based on symptoms and examination ndings, with laboratory and imaging studies as supporting evidence. Morning sti ness lasting at least an hour is one o the major clinical characteristics o all orms o in ammatory arthritis. The morning sti ness o in ammatory arthritis tends to be more di use than that o osteoarthritis (OA). Rheumatoid arthritis is classically symmetric with swelling and tenderness o the small joints o the hands, primarily the wrists, metacarpophalangeal (MCP) joints, and proximal interphalangeal (PIP) joints (Figure 249-2). Other commonly involved joints include the knees, shoulders, ankles, hips, and metatarsophalangeal joints. I arthrocentesis is per ormed, the synovial uid is in ammatory, generally with 2000 to 20,000 white blood cells (WBCs)/mm 3. Classi cation criteria or the diagnosis o RA were last published in 2010 (Table 249-1). These criteria utilize a points system. An individual with ≥ 6 points is classi ed as having RA. Points are given based on number and distribution o involved joints, presence o RF or antiCCP antibodies, elevated acute phase reactants, and duration o symptoms. Anti-CCP antibodies have a sensitivity o 67% and specicity o 95% or the diagnosis o RA; a speci city o 97% or the diagnosis o RA has been reported in patients with early in ammatory arthritis and both positive RF and anti-CCP antibody. Rheumatoid nodules and radiographic erosions are not part o the 2010 criteria, as patients with RA are ideally identi ed and treated be ore either o these mani estations occurs. Rheumatoid arthritis is distinguished rom OA by history and physical examination. Patients with osteoarthritis classically experience

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in the spondyloarthropathies are probably similar to those in RA, the bone proli eration is less well understood. Recent observational studies have shown that while TNF-α inhibitors decrease symptoms and in ammation in spondyloarthropathies, they do not halt bony ankylosis, which must there ore be mediated via di erent pathways.

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peptides may initiate an in ammatory response in the joints. With regard to environmental exposures, cigarette smoking is the strongest proven risk actor or rheumatoid arthritis. Citrullination occurs when, within proteins, the amino acid arginine undergoes posttranslational modi cation, mediated by peptidylarginine deaminases into citrulline. Cigarette smoking may lead to citrullination o proteins in the lungs, rendering them immunogenic. Both citrullinated peptides and antibodies against these peptides have been identi ed in the joints o patients with RA; up to 70% o patients with RA have anti-CCP antibodies in the serum. Rheumatoid actor or IgM anti-IgG antibodies, is detected in approximately 80% o patients. When rheumatoid actors are deposited in joints as immune complexes, they initiate complement-mediated in ammation within the joint. The combination o a positive RF and anti-CCP antibody is >90% speci c or the diagnosis o RA in the right clinical context. However, levels o rheumatoid actor and anti-CCP do not correlate with disease activity in RA, and thus should not be repeated in a positive individual. In RA, the synovium becomes in amed and hypertrophied, and develops into an invasive tissue known as a pannus. The pannus, composed primarily o synovial broblasts, secretes matrix metalloproteinases and other enzymes that erode cartilage and stimulate osteoclasts to erode bone. These processes produce the characteristic radiographic appearance o RA o joint space narrowing and marginal erosions (Figure 249-1). Many current therapies or RA target speci c parts o the in ammatory cascade. Several cytokines, including tumor necrosis actoralpha (TNF-α), interleukin (IL)-1, IL-6, and IL-12, are elevated in rheumatoid joints. Biologic agents are available to inhibit all o these cytokines in RA except IL-12. In ammation in RA is maintained by costimulation o T-cells, which is inhibited by cytotoxic T-lymphocyte-associated protein 4 (CTLA4). T-cell costimulation and activation is inhibited by abatacept, a usion protein consisting o CTLA4 complexed to an immunoglobulin heavy chain (CTLA4-Ig). Spondyloarthropathies and RA have some similar pathogenic mechanisms; both respond to agents that block TNF-α. Bony erosion o joints occurs in both RA and spondyloarthropathies. However, spondyloarthropathies are also characterized by bony proli eration in involved joints and the spine. In these diseases, there is signi cant dysregulation o bone remodeling, such that erosion and proli eration o bone may occur in di erent locations within the same joint. While some mechanisms o joint in ammation and bone erosion

Figure 249 2 Rheumatoid arthritis, with synovitis and ulnar deviation at the metacarpophalangeal joints and atrophy o the interosseous muscles. (Used with permission rom Richard P. Usatine. In: Usatine RP, Smith MA, Mayeaux EJ Jr, et al. Color Atlas o Family Medicine. New York, NY: McGraw-Hill; 2009.) 2047

From the Patient History Duration o symptoms ≥6 wk (1 point)

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TABLE 249-1 The 2010 American College o Rheumatology/ European League Against Rheumatism Classi ication Criteria * From the Patient Examination Synovitis o • 2-10 large joints (1 point) • 1-3 small joints (2 points) • 4-10 small joints (3 points) 10 joints total (5 points)

Laboratory Findings Titers o RF or anti-CCP antibodies that are lowhigher than the upper limit o normal (ULN) but 3 × the ULN (3 points)

These criteria are applied to patients with at least one swollen joint which cannot be explained by another process, such as in ection. Patients with ≥6 total points are considered to meet classi ication criteria or rheumatoid arthritis. CCP, cyclic citrillinated peptide; RF, rheumatoid actor; ULN, upper limit o normal. Extracted rom Aletaha D, et al. 2010 Rheumatoid arthritis classi ication criteria. Arthritis Rheum. 2010;62(9):2569-2581. *

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Elevated sedimentation rate or c-reactive protein, based on lab standards (1 point)

less than an hour o morning sti ness, and may have sti ness a ter prolonged rest and recumbency (inactivity gel phenomenon). Osteoarthritis has a predilection or distal interphalangeal (DIP) joints, PIPs, and the rst carpometacarpal joint (base o the thumb). Large joints including hips, knees, and shoulders are requently involved, as is the lumbar spine in patients with OA. RA, in contrast, classically involves the synovial joint o C1-C2, sparing the remainder o the spine. On physical examination, patients with OA display bony enlargement with less synovial swelling in the small joints o the hands. E usions o larger joints reveal nonin ammatory synovial uid (white blood cell count 4 mEq/L regardless o clinical status. Therapeutic goal is to reduce levels to < 1 mEq/L. Lithium levels should be monitored or 8 to 12 hours a ter dialysis to exclude rebound o lithium reentering the serum rom the intracellular space. Additionally, dialysis may be considered or patients that cannot tolerate uid resuscitation (renal compromise, volume overload, heart ailure). Nephrogenic diabetes insipidus may respond to indomethacin (more e ective in inhibiting renal prostaglandin synthesis than other nonsteroidal drugs and works within a ew hours), thiazide diuretics (acting by mild volume depletion), and amiloride (enhances action o thiazide natriuresis and partially blocks potassium elimination rom concurrent thiazide administration).

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Asymptomatic, stable patients require monitoring or hypotension, bradycardia, and hyperglycemia as these patients may quickly decompensate. Depending on whether the ingested ormulation was immediate-release, standard-release or extended release, a recommended length o observation is 6, 6 to 12, and 24 to 36 hours, respectively. When hypotension does not respond to aggressive uid resuscitation, a combination o IVcalcium, glucagon, high dose insulin, vasopressors, and IVlipid emulsions should be administered. Atropine and glucagon may be administered or symptomatic bradycardia. In patients with mild symptoms, these treatments may be implemented sequentially (every 15 minutes with interval reassessment) whereas multiple therapies should be implemented simultaneously in hemodynamically unstable patients (Table 250-3). Calcium chloride administration requires a central line. More aggressive and invasive therapies are needed, including transvenous pacemaker, intra-aortic balloon pump, cardiopulmonary bypass, and extracorporeal membrane oxygenation (ECMO) i the patient remains hemodynamically unstable despite the a orementioned therapies. Hemodialysis is not e ective since CCBs have large distribution volumes and are highly protein bound.

■ INPATIENT MANAGEMENT

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■ INPATIENT MANAGEMENT

excitability (myoclonic jerks, coarse tremor or seizure). Acute kidney injury may be the cause or the result o acute lithium toxicity. Chronic toxicity will o ten present as nephrogenic diabetes insipidus with accompanying hypernatremia, polyuria, and polydipsia. Chronic toxicity can demonstrate the same neurologic e ects as acute toxicity. Chronic toxicity may also present with a spectrum o pathology including hypothyroidism, hyperparathyroidism with accompanying hypercalcemia. Lithium overdose should be di erentiated rom neuroleptic malignant syndrome, the latter is more likely to cause rigidity. Laboratory evaluation should include serum lithium level, basic metabolic pro le to address renal unction, sodium and calcium levels, and ECG. Lithium levels do not accurately predict toxicity due to slow absorption into the central nervous system. A slight elevation in levels may be associated with lithium toxicity, especially in chronic users.

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overdose leads to decreased cardiac contractility and bradycardia. With higher drug concentrations, however, the L-type channel selectivity is o ten lost so that bradycardia, hypotension, and decreased cardiac contractility may occur due to overdoses rom either CCB category. Negative inotropic e ects may be associated with heart ailure. Ventricular dysrhythmias and mental status changes are usually not seen; however, CNS depression with con usion may be progressing to coma in isolated cases or in patients with re ractory hypotension. β-blocker (BB), clonidine and digoxin ingestions may present similarly and should be considered in the di erential diagnosis. Unlike CCB, clonidine tends to cause miosis and sinus bradycardia rather than high-degree AV block. BBs may cause hypoglycemia whereas CCB may cause hyperglycemia. Basic laboratory data testing begins with the ECG, CBC, CMP, calcium, and cardiac enzymes to exclude cardiac ischemia as a possible etiology o the hypotension or arrhythmia. ECG may reveal bradycardia, PR prolongation, or escape rhythms with advanced AV blocks. Chest x-ray may be obtained to evaluate or pulmonary edema. Digoxin levels should be obtained i concomitant ingestion is suspected. CCB assays are not routinely available and not be part o standard evaluation.

■ NONCYCLIC ANTIDEPRESSANT OVERDOSE Background Noncyclic antidepressants include: • Selective serotonin reuptake inhibitors (SSRIs): uoxetine, ser-

traline, citalopram, escitalopram, paroxetine, and uvoxamine • Serotonin-norepinephrine reuptake inhibitors (SNRIs): venla axine, desvenla axine, and duloxetine • Norepinephrine-dopamine reuptake inhibitors (NDRIs): bupropion, trazodone and mirtazapine These medications are widely prescribed or depression and anxiety disorders. Bupropion is also prescribed or smoking cessation. In general, they are sa e and well-tolerated, especially when compared to TCAs and monoamine oxidase inhibitors (MAOIs). Despite more than 46,000 SSRI overdoses reported in 2011, only two deaths resulted.

Evaluation Clinically, lithium intoxication presents di erently depending on whether it is acute, acute on chronic, or chronic. Acute or acute on chronic lithium toxicity typically presents with gastrointestinal complaints including nausea, vomiting, and diarrhea. Later in the course o acute poisoning, patients develop neurologic complaints including sluggishness, ataxia, con usion/agitation, and neuromuscular

Evaluation Unlike tricyclics none o these drugs have signi cant anticholinergic e ects. Most drugs cause central nervous system depression. Bupropion, a stimulant, may cause seizures due to inhibition or reuptake o norepinephrine and dopamine. Trazodone and mirtazapine can cause hypotension due to peripheral α-adrenergic blockade. SSRI 2061

■ INPATIENT MANAGEMENT OF THE SEROTONIN SYNDROME

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intoxication may lead to seizures and/or serotonin syndrome. SSRIs are well absorbed in the gastrointestinal tract and reach peak levels in 1 to 8 hours. SSRIs inhibit neurotransmitter-speci c pumps that trans er serotonin rom the synapse (where they have their activity) into the cytoplasm o the a erent neuron. They are eliminated by the liver. The hal -li e or the majority o the SSRIs is in the range o 20 to 30 hours, with exceptions being uoxetine (24-72 hours) and uvoxamine (15 hours). A signi cant number o substances e ect serotonergic pathways and can precipitate serotonin syndrome in a patient taking SSRIs (eg, tramadol, cocaine, carbamazepine, St. John’s wort, linezolid, MAOIs, meperidine). This syndrome may develop during hospitalization so must be considered both or newly presenting patients and as a complication arising during the treatment o another disorder. Diagnosis is based on clinical criteria. In order to meet Hunter criteria, the patient must have a history o ingestion o a serotonergic drug and one o the ollowing: spontaneous clonus; inducible clonus or ocular clonus and diaphoresis or agitation; tremor and hyperre exia; hypertonia and temperature greater than 38°C and ocular clonus or inducible clonus. Laboratory evaluation should include CBC, CMP, and CK. An ECG should be obtained to look or QTc prolongation ( uoxetine, citalopram, escitalopram, venla axine). SSRI drug levels are not recommended. There are also many alse positives in urine assays.

Benzodiazepines are the mainstay o therapy to ease agitation and address mild hypertension and tachycardia. A typical starting dose is diazepam 5 to 10 mg IVwith titration to e ect; patients may require repeat dosing q10min. Supportive therapy is aimed at normalizing vital signs. Patients may exhibit severe hypertension or tachycardia, which should be treated with short acting agents (eg, esmolol, nitroprusside). Hyperthermia should be aggressively treated according to the severity. Physical restraints and butyraphones (haloperidol) are not recommended given concern or worsening hyperthermia. Additional supportive care should include IVFs, oxygen and cardiac monitoring. The antihistamine, cyproheptadine, also has serotonergic antagonism although quality evidence is lacking or its ef cacy. See Chapter 92 (Hyperthermia and Fever).

■ TRICYCLIC ANTIDEPRESSANT OVERDOSE Background Though tricyclic antidepressants (TCAs) remain the 12th most common substance associated with atalities rom ingestion despite having been largely supplanted by SSRI’s in the treatment o depression. The therapeutic window is narrow, and TCAs have a hal -li e ranging rom 7 to 58 hours. The drug is rapidly absorbed in the gastrointestinal tract at therapeutic doses and undergoes conversion in the liver to the active metabolite, nortriptyline. Peak levels in the serum or amitriptyline at normal doses are observed at 2 to 5 hours. In the setting o overdose, however, anticholinergic e ects may slow gastrointestinal absorption and delay peak levels. TCAs have wide ranging e ects including: antagonism o cardiac ast sodium channels, anticholinergic and antiadrenergic e ects, antagonism o histamine-1 receptors, and antagonism o central nervous system GABA-A receptors. Evaluation TCAs cause cardiac and neurologic e ects at toxic doses. Cardiac e ects include sinus tachycardia, worsening cardiac dysrhythmias, and hypotension which can be dif cult to control. ECG ndings vary rom widened QRS to QT segment prolongation and ventricular 2062

TABLE 250-4 Treatment Options for TCA Overdose Agent Sodium bicarbonate Benzodiazepines Magnesium Lidocaine Vasopressors (norepinephrine) Hypertonic saline (3%) Lipid emulsion (20%)

Dosing 1-2 mEq/kg bolus, then 150 mEq (in 1 L D5W) at 250 cc/h Varies based on agent 1g IVq6h 1 mg/kg bolus, then 1-4 mg/min in usion Varies based on blood pressure 100 cc bolus (repeat q10min × 3) 1-1.5 mL/kg bolus, then 0.25-0.5 mg/kg/min (up to 8 mL/kg)

Indication QRS >100 ms

Agitation or seizures Re ractory arrhythmia Re ractory arrhythmia Hypotension Hypotension Impending cardiac arrest

brillation. TCAs also may cause a range o neurologic symptoms, including seizures related to GABA-A antagonism. Anticholinergics e ects may lead to delirium, urinary retention, hyperthermia, and dilated, poorly responsive pupils. Antihistaminic activity may cause decreased level o consciousness and even coma. Laboratory evaluation includes ECG, chemistry panel, and troponin. An ABG may be necessary to evaluate acidosis. The 12-lead ECG guides therapy and provides prognostic in ormation. The most sensitive predictor o seizures and ventricular arrhythmias is QRS duration (>0.16 seconds). Serum and urine TCA testing does not reliably guide management or provide prognostic in ormation. Multiple drugs cause alse positive results, signi cant toxicity may occur at nontoxic levels, especially with chronic TCA use, and results are usually not available at the time o clinical decision-making.

■ INPATIENT MANAGEMENT Close cardiac and neurologic monitoring should be in place or admitted patients. Telemetry and serial 12-lead ECG monitoring is recommended or patients with sinus tachycardia. ICU admission should be considered i ECG changes (including QRS prolongation, prolonged QTc, tall R waves in AVR or AVR R/S >0.7, arrhythmias), hypotension, respiratory depression, or altered mental status. Treatment agents should be targeted by indication (Table 250-4). SEDATIVE AND ALCOHOL

■ SEDATIVE AND ALCOHOL INTOXICATION Background Sedatives constitute a diverse group o agents, including alcohol, benzodiazepines, nonbenzodiazepine hypnotic medications (socalled Z-drugs such as zolpidem [Ambien]), barbiturates, and several other compounds, including chloral hydrate and meprobamate. All sedatives dose-dependently depress neuronal unction, and most o these agents can produce atal respiratory depression. Evaluation Both alcohol intoxication and sedative overdose present with uncoordinated motor unctioning (gait ataxia, nger to nose incoordination, positive Romberg sign), nystagmus, slurred speech, and various aberrant behaviors, including behavioral disinhibition, impairment o consciousness, reduced respirations, and drowsiness or sleep. Memory disturbances and rank amnesia, requently re erred to as

C H A P T E R 2 5 0 D r u g

Signs Tachycardia Hypertension Tremor Sweating Vomiting Generalized tonic-clonic seizures

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Symptoms Anxiety/nervousness Gastrointestinal distress Headache Bad dreams Insomnia Sensory disturbances Nausea Fatigue

■ INPATIENT MANAGEMENT With alcohol intoxication, neurologic symptoms should clear within 4 hours unless due to coingestions, head trauma, or other causes. With any sedative overdose, the management is supportive and may require a period o arti cial ventilation until the sedative level alls and spontaneous respiration resumes. A benzodiazepine antagonist, umazenil, competitively binds but does not activate the gamma-aminobutyric acid (GABA) benzodiazepine receptor. The use o umazenil may precipitate seizures in individuals who have developed physiologic dependence on benzodiazepines; there ore, this drug should only be used in consultation with a toxicologist (eg, Poison Control).

■ SEDATIVE AND ALCOHOL WITHDRAWAL Background Use o a sedative or alcohol on a daily basis or more than 2 weeks may result in withdrawal upon cessation o use. The likelihood increases with longer periods and heavier use. Withdrawal can also occur with nondaily, binge pattern use (more days o the week than not). The common signs and symptoms o alcohol withdrawal are shown in Table 250-6 and delirium tremens (DTs) are shown in Table 250-7. In general, withdrawal rom sedatives produces similar

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blackouts, are more likely with short-acting sedatives, alcohol, or a combination o the two. The history, either directly rom the patient or rom his or her associates, usually provides suf cient evidence to con rm intoxication with alcohol or sedatives. Laboratory testing in these patients should include a blood alcohol level (Table 250-5) obtained directly rom a serum sample or indirectly by measurement o the breath alcohol content with a breathalyzer. A metabolic pro le should be obtained to check blood glucose (malnourished patients may have hypoglycemia) and to calculate the anion gap. Other toxic alcohols (ethylene glycol [anti reeze], methanol [wood alcohol]) will cause a high anion gap acidosis and osmolar gap. Isopropyl alcohol is associated with an elevated osmolar gap but not with an elevated anion gap acidosis (see Chapter 238 [Acid Base Disorders]). Urine testing or benzodiazepines and barbiturates is widely available. Standard assays or benzodiazepines do not detect benzodiazepines but rather metabolites o 1,4-benzodiazepines. Thereore, they vary in their sensitivity to detect some benzodiazepines (clonazepam, lorazepam, midazolam, or alprazolam). Urine tests or other sedatives, including the Z-drugs and older sedatives (eg, meprobamate, chloral hydrate, ethchlorvynol), are not widely available, although may be requested rom outside laboratories. Serum benzodiazepine levels do not correlate with clinical ndings and are not readily available during emergent management.

signs and symptoms as withdrawal rom alcohol. Barbiturates and other, older sedatives may be more likely to produce seizures and/or delirium during withdrawal. The syndromes di er principally in their time course, which is directly correlated with the elimination hal -li e o the agent. Long-acting sedatives, such as diazepam or phenobarbital would typically present more gradually than alcohol withdrawal, and with a later onset o withdrawal seizures and peak symptoms. Alcohol withdrawal typically progresses through stages due to central nervous system hyperactivity:

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Effects Mellow, warm, less inhibited Relaxed, less alert, early coordination impairment De inite impairment in coordination, judgment Noisy, decreased reaction time, mood swings, embarrassing behavior Clearly drunk, impaired balance and movement Many pass out Most pass out, some die Breathing stops, many die

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BAC (g/dL) 0.02 0.05 0.08 0.10

TABLE 250-6 Common Signs and Symptoms of Mild to Moderate Alcohol Withdrawal

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TABLE 250-5 Common Effects at Various Blood Alcohol Concentration Levels in Nontolerant Individuals

• 6 to 12 hours a ter last drink: tremulousness (in up to 100%

o individuals) and other minor symptoms (insomnia, anxiety, gastrointestinal upset, headache) • 12 to 48 hours a ter last drink: withdrawal seizures occurring predominantly in patients with a long history o heavy alcohol use or prior withdrawal seizures • 12 to 48 hours a ter last drink: alcoholic visual hallucinations without mental status changes or hemodynamic instability (in up to 25% o individuals) • 2 to 4 days a ter last drink: delirium tremens (in 4%-5% o patients) Other causes o symptoms suggesting DTs that do not respond to high doses o benzodiazepines or last more than a week include intoxication due to benzodiazepines, gamma hydroxybutyrate (GHB) or baclo en withdrawal. Evaluation Laboratory evaluation should include complete blood count with di erential and platelet count, coagulation tests, comprehensive

TABLE 250-7 Signs and Symptoms of Delirium Tremens (DTs) Delirium Con usion Disorientation Behavioral agitation Waxing/waning o consciousness Severe autonomic instability Tachycardia Hypertension Diaphoresis Fever (low grade) Arrhythmias Hallucinations Visual more common than tactile (rarely auditory)

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metabolic pro le, liver biochemical tests, amylase or lipase, ECG, urinalysis, and in selected patients cultures. The ECG should be examined to determine QTc interval (prior to initiating possible treatment with haloperidol) and to identi y possible ischemia. Ethanol levels are usually low or undetectable and do not in uence management. Patients may experience withdrawal signs and symptoms with an elevated blood alcohol level.

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INPATIENT MANAGEMENT All patients should receive thiamine be ore glucose administration to avoid causing Wernicke’s encephalopathy (encephalopathy, oculomotor dys unction, gait ataxia), olate, multivitamins, intravenous hydration, correction o electrolyte disorders (especially magnesium and potassium depletion). For alcohol withdrawal, the most important element o management is prevention o seizures and DTs. Management o DTs commonly requires admission to an intensive care unit, or very close monitoring o vital signs and administration o high doses o benzodiazepines or barbiturates with or without adjunctive haloperidol. The general approach is to substitute an adequate dosage o a long-acting benzodiazepine (eg, diazepam, chlordiazepoxide, or clonazepam) to alleviate withdrawal symptoms. Some experts avor the use o lorazepam because it is not metabolized in the liver and would there ore not accumulate in patients with severe liver disease; however, metabolic unction is usually well preserved until severe end-stage liver disease is present. Lorazepam’s principal advantages are that it is available as a parenteral agent, and its short hal -li e allows rapid titration. Administering more than one benzodiazepine will complicate management due to di erent hal -lives and should be avoided. Table 250-8 provides a range o suggested doses o several common benzodiazepines and phenobarbital or use in mild to moderate alcohol withdrawal. A xed dose regimen or a symptom-triggered approach is used to establish the benzodiazepine taper. The symptom-triggered approach can minimize the total dosage o benzodiazepines utilized, but may be too labor intensive to be practical in some settings. As such, a xed- exible dose regimen may be pre erred. Clinical Institute Withdrawal Assessment or Alcohol (CIWA) is a widely used scoring system that may be used at the bedside with set protocol orms or online (http://www.reseau ranco.com/ en/ assessment_and_treatment_in ormation/ assessment_tools/ clinical_institute_withdrawal_assessment_ or_alcohol_ciwa.pd ).

TABLE 250-8 Common Initial Dose Ranges for Benzodiazepines in Alcohol Withdrawal Benzodiazepine Chlordiazepoxide † Lorazepam Diazepam † Clonazepam † Barbiturate Phenobarbital†

Mild Withdrawal* 25-50 mg every 6 h 1-2 mg every 6 h 10-20 mg every 6 h 0.5-1 mg every 6 h

Moderate Withdrawal 75-100 mg every 6 h 3-4 mg every 6 h 30-40 mg every 6 h 1.5-2 mg every 6 h

30-60 mg every 6 h

90-120 mg every 6 h

Note that these initial doses will not be su icient or some patients; those patients who consume large quantities o alcohol (typically > 10-15 standard drinks daily) may need larger doses than those listed here. † These long-acting agents allow a more rapid taper than shorter-acting agents, so that individuals may be tapered o their medication in as little as 4 or 5 d. These long-acting sedatives can accumulate; individuals should be observed care ully or signs o oversedation i these starting doses are not tapered within a ew days. *

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A score 8 supports withdrawal and need or intervention with an aim to achieve a score less than 8 by inducing a light sleep with benzodiazepines. Once stabilized, most patients can be tapered o benzodiazepines in approximately 10 days, with dosage reductions o approximately 10% o the total daily dosage each day over the course o those 10 days (which can be completed as an outpatient). Withdrawal rom alcohol may also be managed very e ectively with a long-acting barbiturate (phenobarbital), again with the need rst to stabilize the patient’s vital signs and eliminate other withdrawal signs and symptoms, ollowed by a taper schedule over approximately 10 days. There is some evidence that alcohol withdrawal may also be managed with anticonvulsants (carbamazepine, gabapentin, valproic acid, and others), either in conjunction with benzodiazepines or as a standalone therapy, although the evidence thus ar or anticonvulsants in alcohol withdrawal is insuf cient to support their use over benzodiazepines. Withdrawal rom sedatives is more complicated than withdrawal rom alcohol. Long-term use ( or more than 6 months) o benzodiazepines and Z-drugs, even at modest dosages, may be associated with a greater risk o seizures or days to weeks ollowing cessation. As a result, many physicians recommend a sedative taper over several months under the supervision o a psychiatrist or addiction specialist. This may best be accomplished by switching a patient to phenobarbital and tapering it gradually over several months. Adjunctive use o anticonvulsants may play a role to reduce the seizure risk, but the evidence or this is limited. Withdrawal rom barbiturates and other sedatives cannot sa ely be sa ely managed using benzodiazepines, because benzodiazepines do not adequately reduce the risk o seizures or withdrawal delirium. As such, phenobarbital is the agent o choice or managing withdrawal rom barbiturates and other sedatives. Mixed sedative dependence syndromes, in which individuals regularly ingest multiple agents and possibly alcohol, should be managed with phenobarbital because it will sa ely cover withdrawal symptoms rom all sedatives and alcohol. ANALGESICS

■ ACETAMINOPHEN OVERDOSE Acetaminophen is an analgesic drug, commonly used in combination with other drugs. The active ingredient is acetyl-para-aminophenol (APAP). The amount o acetaminophen ingested and the time to presentation are the most important prognostic indicators o hepatotoxicity. The APAP level guides therapy. The biggest bene t o N-acetylcysteine is within 12 hours o ingestion; however, treatment should be initiated or any toxic APAP level (see Chapter 100 [Suspected Intoxication and Overdose], Chapter 109 [Elevated Liver Biochemical and Function Tests], and Chapter 159 [Acute Liver Disease]).

■ SALICYLATE OVERDOSE Salicylates are ound in a number o medications, including aspirin products, bismuth subsalicylate (Pepto-Bismol) and herbal medications. Salicylate poisoning should be considered in any patient with an elevated anion gap acidosis. Serum salicylate levels may not correlate with clinical presentation due to a number o actors, including delayed absorption o enteric-coated ormulations, altered absorption and elimination ollowing overdose, and salicylate redistribution in body tissues rather than excretion by the kidneys. Available through poison control, a medical toxicologist should be consulted in any patient suspected o salicylate poisoning. Consider consultation with a nephrologist or guidance on alkalinization to

Methadone

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■ INPATIENT MANAGEMENT Overdose may occur in new opioid users, as part o a suicide attempt, when drug purity is unexpectedly high, or during induction on a long-acting opioid (eg, methadone). Injection drug users are particularly vulnerable to overdose when getting opioids rom a new source where drug purity is not known and there is a mixture multiple drugs such as entanyl and heroin. Initial treatment includes the use o the short-acting injectable opioid antagonist naloxone and supportive care. In the opioid-naïve individual, ull-agonist reversal generally occurs when 0.4 mg o naloxone is given (IV/IM/ SQ/ET) every 2 to 3 minutes. The intravenous route provides the most predictable response. For opioid-dependent patients, smaller doses should be used and titrated to reverse respiratory depression

TABLE 250-9 Opioid Withdrawal Symptoms and Time Course (Short-acting Opioids)

12-18 18-24 > 24

Signs and Symptoms Lacrimation, yawning, pupil dilation, rhinorrhea, sweating Irritability, anxiety, nausea, sleep problems Abdominal cramps, restlessness, anorexia, piloerection, tremor Vomiting, diarrhea, muscle spasms, tachycardia, chills, hyperthermia, severe insomnia

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Inpatient Management Management o the opioid withdrawal syndrome (OWS) should be based on patient characteristics, goals o treatment, and local resources. Always veri y methodone dosage prior to administration o large doses in patients who chronically take methadone. Patient characteristics include determination o the presence or absence o pain (acute and chronic), the presence or absence o pathologic opioid use (abuse and addiction), the type and amount o opioid being used, and the cause and severity o withdrawal. The goal o treatment will be either stabilization on an opioid, or complete cessation o all opioids. For opioid-addicted patients who are not currently receiving addiction treatment, the presence or absence o pain is the primary determinant o medication selection. Patients with pain will require agonist treatment with buprenorphine, methadone, or other opioid agonists. Patients without pain (other than withdrawal pain) can be managed with clonidine or buprenorphine. Medications most commonly used or the treatment and symptom management o OWS are outlined in Table 250-10 and Table 250-11.

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Fever, dyspnea, and acute pain are common presenting complaints o opioid-using patients. Underlying in ection is o ten the cause o these complaints, particularly among injection drug users (IDUs). Endocarditis, skin, and so t-tissue in ections, bone and joint in ections, epidural abscess, and even pneumonia are more common among IDUs than in general medicine patients. When an opioid user is identi ed, a key part o the evaluation is to determine i the individual is physically dependent on opioids. The role o urine drug testing in the diagnosis o opioid use is airly limited. Providers need to be aware o general test characteristics as well as what tests are locally available. Speci c (and separate) urine radioimmunoassay screening tests can be used to screen or opiates, oxycodone, meperidine, propoxyphene, and methadone metabolites. A “negative” screening test never rules out opioid use, and a “positive” screening test can only be used to support a clinical diagnosis. De nitive testing can be per ormed with gas chromatography/mass spectroscopy, but such testing is expensive and results are not immediately available. Patients may present with symptoms o overdose (lethargy, pinpoint pupils, respiratory depression) or withdrawal (sweating, tremor, tachycardia, anxiety, pupillary dilation). Withdrawal symptoms typically begin 6 to 12 hours a ter the last use and will peak at 24 to 48 hours, but vary based on agent (Table 250-9).

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Evaluation

Hours After Last Opioid Use 6-12

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Every 2-4 h

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30-40 mg

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Every 6-8 h

D

Buprenorphine

Typical Doses 0.1-0.2 mg orally 10-20 mg orally 2-4 mg

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Medication Clonidine

Maximum Daily Dose 1.2 mg

R

Background

Typical Dosing Intervals Every 2-6 h

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■ OPIATE OVERDOSE

5

TABLE 250-10 Typical Medication Dosing Regimens for Treatment of the Opioid Withdrawal Syndrome

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promote elimination o salicylate and or recommendations and timing o possible hemodialysis.

STIMULANTS

■ STIMULANT OVERDOSE Background There are many types o abused stimulants in the United States, including cocaine, amphetamines, ecstasy, and over-the-counter and prescription stimulants. Table 250-12 outlines the most commonly abused stimulants. Prescription stimulants include methylphenidate, methamphetamine, dextroamphetamine, mazindol, phenmetrazine, and phentermine. Prescribed stimulants may be used therapeutically

TABLE 250-11 Medications for Symptomatic Treatment of Acute Opioid Withdrawal Symptom Sleep problems Myalgia Diarrhea Abdominal cramps

Medication Zolpidem, temazepam, trazodone Acetaminophen, nonsteroidal anti-in lammatory drugs Loperamide Dicyclomine

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Street Name Amphetamines Bennies, peaches Black Beauties, crank, cristy, crystal, crystal meth, meth, pep pills, quartz, speed, uppers, white crosses Cramming drug, R-ball, rits, vitamin R Dexies, ootballs Ice, crystal Cocaine preparations Crack, rock, gravel, supercoke Big C, blow, coke, lake, lave, nose candy, snow, sugar boogers, white lady Pasta, bazooka Designer drugs Ecstasy, XTC, Adam, M&M, Stars, 007s Eve

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TABLE 250-12 Commonly Abused Stimulants

The love drug STP (serenity, tranquility, peace), sweet tart Cathinone/cathine A rican salad, Bushman’s tea, chat, kat, qat Cat Drug combinations C&M Death hit Goo ball, snowball, speedball Ice Liquid lady Pineapple Poor man’s speedball Snackies Space ball, space base, space dust Speedboat Speedies Super Xs

Drug(s) [Trade Name] Amphetamine sul ate [Benzedrine] Methamphetamine [Methedrine, Desoxyn]

Methylphenidate [Ritalin, Concerta] Dextroamphetamine [Dexedrine, Dextrostat] Freebase (smokable) methamphetamine Freebase (smokable) cocaine Cocaine HCl

Physiologic Effects Dizziness Tremor Hyperre lexia Hyperpyrexia Mydriasis Tachypnea Tachycardia Hypertension

Psychological Effects Grandiosity Restlessness Hypervigilance Aggression Impaired judgment Stereotyped behavior

Toxic Effects Hyperthermia Seizures Rhabdomyolysis Acute renal ailure Hepatotoxicity Increased myocardial oxygen consumption Disseminated intravascular coagulation

Methylenedioxymethamphetamine (MDMA) Methylenedioxyethamphetamine (MDEA) Methylenedioxyamphetamine (MDA) Dimethoxymethamphetamine (DOM)

vasoconstriction, increased heart rate, and lowered seizure threshold. Psychological e ects result rom stimulation o corticomesolimbic dopamine circuits in the brain, leading to desired e ects (increased energy and alertness, euphoria, decreased appetite and need or sleep) as well as negative e ects (anxiety, grandiosity, impaired judgment, psychosis, paranoid delusions and hallucinations, and addiction). Adrenergic poisoning syndromes have similar presentations to neuroleptic malignant syndrome, serotonin syndrome, thyroid storm, intracranial hemorrhage, and pheochromocytoma. Laboratory evaluation includes urine drug screen, CBC, CMP, creatine kinase, urinalysis, coagulation tests, liver biochemical tests, troponins, ECG, and CXR. Additional testing may include thyroid unction tests and neuroimaging. Stimulant overdose symptoms are outlined in Table 250-13.

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■ INPATIENT MANAGEMENT

Coca paste

methcathinone Cocaine + marijuana Cocaine + strychnine Cocaine + heroin Methamphetamine + reebase cocaine Cocaine + alcohol Methylphenidate + heroin Methamphetamine + heroin MDMA + mescaline Cocaine + phencyclidine Freebase cocaine + marijuana + phencyclidine (all smoked together) MDMA + amphetamine MDMA + methamphetamine

or multiple conditions, including attention-de cit disorder, narcolepsy, atigue in multiple sclerosis, and re ractory depression, as well as in palliative care. Nicotine and ca eine are mild stimulants that are also in widespread use. Evaluation Stimulant overdose usually presents with symptoms due to overstimulation o the sympathetic nervous system leading to peripheral 2066

TABLE 250-13 Stimulant Intoxication Signs and Symptoms

Treatment or acute overdose o stimulants includes stabilization o airway, breathing, and circulation, administration o activated charcoal, seizure control with benzodiazepines, aggressive management o hypertension, and management o hyperthermia. The acutely intoxicated stimulant user should be approached in a subdued manner. Speci c management or cocaine-associated complications is outlined in Table 250-14. Designer drugs, especially MDMA (ecstasy), are stimulants with some hallucinogen-like e ects, so acute physiological e ects include more pronounced hypertension and hyperthermia as compared to other hallucinogens. MDMA also has serotonergic e ects. Peak e ects occur within 2 hours ollowing ingestion and e ects last approximately 4 to 6 hours. Ecstasy o ten contains adulterants. Urine drug screen will be positive or amphetamines but a negative screen does not exclusion ingestions o this drug. Hyperthermia is the main cause o death. Toxicity o designer drugs may be related to additives such as ketamine or LSD. There are numerous case reports o MDMA use resulting in hyperthermia, rhadomyolysis, serotonin syndrome, hyponatremia with cerebral edema, ulminant hepatic ailure, and stroke. Other stimulant-derived hallucinogens may cause cardiac arrhythmias.

■ STIMULANT WITHDRAWAL The severity and duration o withdrawal rom stimulants depends upon the intensity o the preceding months o chronic abuse and the presence o predisposing psychiatric disorders. In general, the “crash,” or drastic reduction in mood and energy, can start within minutes a ter the last use. The user experiences craving, depression, irritability, anxiety, and paranoia. The craving or stimulants

Adapted, with permission, rom Hollander JE, Ho man RS. Cocaine. In: Gold rank LR, Flomenbaum NE, Lewin NA, et al, eds. Goldfrank’s Toxicologic Emergency, 7th ed. McGraw Hill; 2002.

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Patients may be admitted to a hospital with an overdose, intoxication, or withdrawal syndrome rom drugs o abuse, including marijuana, hallucinogens, “club drugs,” and/or inhalants. Marijuana is the most requently abused drug in the United States, with a prevalence o around 4% o the adult population. The most widely used hallucinogen is LSD, with a li etime prevalence o use o 14% among young adults. Among club-going young adults, use o hallucinogens is up to 70%. Common “club drugs” are listed in Table 250-15.

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■ BACKGROUND

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OTHER DRUGS OF ABUSE

■ EVALUATION

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Oxygen Diazepam 5-10 mg IVor lorazepam 2-4 mg IV Aspirin 325 mg Nitroglycerin 0.4 mg 3 times, every 5 min, ollowed by an in usion titrated to a mean arterial pressure reduction o 10% or relie o chest pain Phentolamine 1 mg IV; repeat in 5 min Verapamil 5-10 mg IV Heparin 60 units/kg bolus, ollowed by 12 units/kg/h Percutaneous intervention (angioplasty and stent placement) or ibrinolytic therapy or STEMI [ST-segment-elevation myocardial in arction] Glycoprotein IIb/IIIa inhibitors Supraventricular Oxygen tachycardia Diazepam 5 mg IVor lorazepam 2-4 mg IV Adenosine 6 mg or 12 mg IV Consider diltiazem 20 mg IVor verapamil 5 mg IV Cardioversion i hemodynamically unstable Ventricular Oxygen dysrhythmias Sodium bicarbonate 1-2 mEq/kg Lidocaine 1.5 mg/kg IVbolus ollowed by 2 mg/min in usion Diazepam 5 mg IVor lorazepam 2-4 mg IV De ibrillation i hemodynamically unstable Hypertension Observation Diazepam 5-10 mg IVor lorazepam 2-4 mg IV titrated to e ect Phentolamine 1 mg IV; repeat in 5 min Nitroglycerin or nitroprusside continuous in usion titrated to e ect Pulmonary Lasix 20-40 mg IV edema Nitroglycerin in usion titrated to blood pressure Consider phentolamine or nitroprusside Anxiety and Diazepam 5-10 mg IVor lorazepam 2-4 mg IV agitation titrated to e ect Seizures Diazepam 5-10 mg IVor lorazepam 2-4 mg IV titrated to e ect Phenobarbital 25-50 mg/min up to 10-20 mg/kg Intracranial Neurosurgery consultation hemorrhage avoid β-blockers or blood pressure control Hyperthermia External cooling measures Paralysis to reduce heat generation Ventilation with high oxygen concentrations Acute renal Vigorous luid replacement ailure Alkalinization o the urine Consider mannitol

a

Acute coronary syndrome

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TABLE 250-14 Treatments for Acute Medical and Neuropsychiatric Effects of Cocaine

decreases over several hours and is replaced by a need or sleep and ood. Hypersomnolence lasts between 8 hours and 4 days. Sleep is interrupted by brie awakenings during which the user experiences hyperphagia (“the munchies”). This phase is ollowed by a protracted dysphoric syndrome consisting o anhedonia, boredom, anxiety, panic attacks, generalized malaise, problems with memory and concentration, and occasional suicidal ideation. This induces severe craving that may lead to resumption o stimulant use and a vicious cycle o recurrent binges. Withdrawal syndromes or stimulants require only supportive care.

Indicators that would raise the suspicion o the use o these drugs are outlined in Tables 250-16 and 250-17.

■ INPATIENT MANAGEMENT Treatment tips or the management o acute overdose o marijuana and hallucinogens are outlined in Table 250-18. For PCP, hypertension should be treated vigorously with intravenous antihypertensives, since it may cause hypertensive encephalopathy or intracerebral bleeding. PCP can also cause li e-threatening hyperthermia with temperatures over 106°F; rapid cooling measures (ice packs, cooling blanket, etc) may be required. Psychotic behavior can be treated with haloperidol. I the patient is severely agitated and poses a potential threat to sel or others, haloperidol or lorazepam is e ective or control o agitation; barbiturates may be even more use ul in this setting with this drug, according to some reports. GHB overdose may cause severe central nervous system and respiratory depression that abates over several hours. For acute GHB intoxication, supportive care includes oxygen supplementation, intravenous access, and comprehensive physiologic and cardiac monitoring. Providers should attempt to keep the patient stimulated and awake. Atropine may be used or persistent symptomatic bradycardia. Naloxone and umazenil are ine ective, and activated charcoal is contraindicated due to the risk o aspiration and the short hal -li e o GHB. The most dangerous e ects o GHB use o ten occur with the use o other drugs. Concurrent use o sedatives or alcohol may increase the risk o vomiting, aspiration, or cardiopulmonary depression; the use o GHB and stimulants may increase the risk o seizure.

■ WITHDRAWAL Heavy marijuana use or more than 3 weeks results in a withdrawal syndrome a ter abrupt cessation and consists o irritability, agitation, depression, insomnia, nausea, anorexia, and tremor that can last or weeks. Marijuana withdrawal is uncom ortable but not li e threatening; treatment is entirely supportive and rarely requires adjunctive medications. Withdrawal rom GHB is similar to withdrawal rom sedatives such as benzodiazepines and alcohol; symptoms start within 6 2067

Chemical Name Alprazolam Dextromethorphan (DXM) Diazepam

Brand Name(s) Xanax Coricidin, Robitussin Valium

NIDA Club Drug No No No

Flunitrazepam Gamma-hydroxybutyrate (GHB)

Rohypnol Xyrem

Yes Yes

Hydrocodone Ketamine

Hycodan, Lortab, Vicodin Ketalar

No Yes

Slang Names Blue haze, X Dex, DXM, Robo, Triple C’s Downers, Mother’s little helper, V’s Mexican Valium, Roo ies, rope Georgia Home Boy Grievous Bodily Harm, Liquid Ecstasy Hykes, Vike Special K, kit cat, cat valium

Yes

Acid, blotter, microdot

Opioid Arylcyclohexylamine Hallucinogen Prototypical Hallucinogen

Yes Yes

Crank, crystal meth, ice, speed Ecstasy, X

Stimulant Designer Drug Stimulant

Rits, smart pills, vitamin R Hillbilly heroin, OC, Oxy, Perc Suzie

Stimulant Opioid Stimulant (OTC)

Lysergic acid diethylamide (LSD) Methamphetamine Methylenedioxymethamphetamine (MDMA) Methylphenidate Oxycodone Pseudoephedrine

Desoxyn

Ritalin No OxyContin, Percocet, Tylox No Suda ed No

Drug Type Benzodiazepine Sedative Opioid (OTC) Benzodiazepine Sedative Benzodiazepine Sedative Sedative

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i

t

t

e

S

t

n

e

i

t

a

p

n

I

e

h

t

n

i

s

n

o

i

t

i

d

n

o

C

l

a

c

i

n

i

l

C

I

V

T

R

A

P

TABLE 250-15 Common “Club Drugs”

hours o the last use, then increase in intensity over several hours to days and may persist or 2 weeks. Physiologic signs include diaphoresis, tremor, tachycardia, and hypertension. Other symptoms are nausea with vomiting, anxiety, restlessness, insomnia, and “ eelings o doom.” Severe withdrawal involves agitation, delirium, and

psychosis. GHB withdrawal may not respond to benzodiazepines despite very high doses. Antipsychotics or pentobarbital may have some utility in treatment o severe GHB withdrawal, although antipsychotics may lower the seizure threshold, especially when used without a sedative.

TABLE 250-16 Findings that Raise the Suspicion of Drug Use

TABLE 250-17 Signs and Symptoms of Hallucinogen Intoxication

Finding Conjunctival injection Tachycardia Pinpoint pupils Vertical nystagmus Nasal septal per oration Sores, hyperpigmentation around mouth and/ or nose New murmur Track marks, resh needle marks White blood cell count low Transaminases (alanine aminotrans erase, aspartate aminotrans erase) elevated Urine drug screen positive

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Medical Indication Current use Intoxication Intoxication, overdose Intoxication Vasoconstriction Chemical irritation

Endocarditis rom injection drug use Injection drug use

Drug(s) Marijuana Opioids Phencyclidine Any snorted drug Inhalants

Any injected drug

Human immunode iciency virus Viral hepatitis

Recent drug use

Marijuana, phencyclidine, stimulant, opioid, benzodiazepine

Perceptual Distortions Light trails behind moving objects Micropsia (the sensation that the user is very large in relation to the surroundings) Macropsia (the sensation that the user is very small in relation to the surroundings) Synesthesias (cross-linking o the ive senses [eg, “see the sounds, taste the colors”]) Sensation that the body is made o wood, plastic, or rubber Out-o -body experiences (sensation o loating over or outside one’s physical body) Sense o pro ound understanding or universal connection Feeling o impending doom

Psychiatric Effects Anxiety Depression Paranoia Impaired judgment Ideas o re erence (getting personal messages rom the television or radio) Depersonalization (“I am not real”) Derealization (“The environment is not real”)

Physiologic Effects Pupillary dilation Tachycardia Diaphoresis Tremulousness Lack o coordination Hyperre lexia Seizures Hyperthermia

Decker BS, Gold arb DS, Dargan PI, et al. Extracorporeal treatment or lithium poisoning: systematic review and recommendations rom the EXTRIP workgroup. Clin J Am Soc Nephrol. 2015;10(5):875-887.

Shenoy S, Lankala S, Adigopula S. Management o calcium channel blocker overdoses. J Hosp Med. 2014;9(10):663-668.

Glauser, J. Tricyclic antidepressant poisoning. Cleve Clin J Med. 2000;67(10):704-706, 709-713, and 717-719.

Strassman RJ. Adverse reactions to psychedelic drugs: a review o the literature. J Nerv Ment Dis. 1984;172:577-595.

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Shannon MW, Borron SW, Burns M, eds. Haddad and Winchester’s Clinical Management of Poisoning and Drug Overdose, 4th ed. Philadelphia, PA: Saunders; 2007.

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Boyer, EW. Management o opioid analgesic overdose. N Engl J Med. 202;367:146-155.

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Reilly TH, Kirk MA. Atypical antipsychotics and newer antidepressants. Emerg Med Clin North Am. 2007;25(2):477-497.

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Bari K, Fontana RJ. Acetaminophen overdose: what practitioners need to know. Clin Liver Dis. 2014;4(1):17-21.

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SUGGESTED READINGS

Olson, KR. Poisoning and Drug Overdose, 6th ed. New York, NY: the McGraw-Hill Companies; 2012.

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Mowry JB, Spyker DA, Cantilena LR, et al. 2013 Annual report o the American association o poison control centers’ National Poison Data System (NPDS): 31st Annual report. Clin Toxicol. 2014;52: 1032-1283.

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Mokhlesi B, Leikin JB, Murray P, et al. Adult toxicology in critical care; Part II: speci c poisonings. Chest. 2003;123:897-922.

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Kosten TR, O’Connor PG. Management o drug and alcohol withdrawal. N Engl J Med. 2003;348(18):1786-1795.

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period o relative lucidity. • Maintain contact through periods o anxiety and perceptual distortion. • Administer benzodiazepine (lorazepam, diazepam) or severe anxiety. • Consider low-dose haloperidol or severe psychotic reactions (but may lower seizure threshold).

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• Establish contact with a gentle touch (hold hand) during a

Gupta A, Lawrence AT, Krishnan K, et al. Current concepts in the mechanisms and management o drug-induced QT prolongation and torsade de points. Am Heart J. 2007;153:891-899.

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• Settle the intoxicated patient in a quiet environment.

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TABLE 250-18 Treatments for Acute Intoxication of Marijuana and Hallucinogens

Grandjean EM, Aubry JM. Lithium: Updated human knowledge using an evidence-based approach Part III: clinical sa ety. CNS Drugs. 2009;23(5):397-418.

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CHAP TER

Addiction of Prescription and Nonprescription Drugs Mary Eno, MD, MPH

Key Clinical Questions

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1

Why do not they just stop using?

2

Why do they start using?

3

Is my patient addicted?

4

How can I help my addicted patient?

5

Why did my patient leave against medical advice?

6

What treatments are available?

7

Does addiction treatment work?

INTRODUCTION Patients with addiction can ba e and overwhelm even the most compassionate physicians, and these patients sometimes even deceive themselves into believing there is no problem. The symptoms o drug and alcohol use can mimic or co-occur with mental illness and chronic pain, complicating the diagnosis. Families can play a role in the development o addiction and also in its treatment. Fortunately, addiction is a treatable disease o the brain. Physicians have a unique opportunity to intervene in the addictive process and shepherd our patients—and our colleagues—into treatment when needed. The brain is hardwired to reward behaviors that enhance survival o the individual or the species. The reward is pleasure, and it happens when dopamine levels rise in the limbic system. For example, eating when you are hungry, drinking water when you are thirsty, or having sex releases dopamine, which is subjectively experienced as pleasurable. People are motivated to seek pleasure and avoid pain in order to survive. Every behavior you per orm is related to pain avoidance or short- or long-term pleasure reward. Drugs o abuse—including alcohol, nicotine, illicit drugs, and some prescription medications—are potentially dangerous because they raise the dopamine in the limbic system aster, longer, and much higher than any natural reward (such as ood, sex, or seeing your amily). The brain, which is motivated to seek immediate reward, drives an individual’s behavior to repeat the intense pleasure as much as possible. Dopamine also enhances learning and classical conditioning, so a person with an addiction unconsciously learns the pleasurable “survival value” o the drug. I the drug use continues, it essentially hijacks the brain’s motivational dopamine system, tricking the brain into behaving as though the individual needs the drug to survive. At this point, the individual becomes dominated by seeking and repeating drug use. Changes take place in the brain that make it extremely uncom ortable to be without the drug. Natural dopamine production downregulates, and the brain becomes less responsive to dopamine presence. This is known as tolerance, meaning more o the drug is needed to produce a pleasurable sensation. It also means that previously pleasurable activities are no longer grati ying. The relative absence o dopamine leads to dysphoria in the absence o rein orcing drugs. Taking the drug is the astest and easiest way or an addicted person in withdrawal to eel “normal” again. Eventually, continuing drug use overwhelms voluntary control and crowds out other relationships, becoming more important than an individual’s amily, values, even ood and sex. At this point, drug and alcohol users isolate rom other people to ocus more obsessively on drug use. When addiction progresses to this level, people may use any means necessary—including manipulation, deceit, sometimes even violence—to obtain the drug o choice. Survival instincts can override judgment and moral values. This is why “drug seeking” patients can seem so di cult. The brain is motivated to survive, and ollowing the brain changes o chronic drug use, survival equals continued use. In late-stage addiction, a patient’s body has usually become so used to the presence o the drug that the patient reports needing the drug to eel “normal.” Without the drug, the patient will become increasingly uncom ortable and anxious until nothing in the environment can prevent the person rom using. At that point, asking an addicted person to stop drinking or using is like asking you to stop breathing. I you were to voluntarily stop breathing, your hypoxic

Alcoholic and addicted patients are requently in denial, meaning they honestly believe they do not have a problem; or they may desire very strongly to stop, but nd they cannot stop because the biological motivation to use has become so strong. In addition, patients may not even remember some o the consequences o their use i they were intoxicated to amnesia (“blackouts”)— particularly with alcohol. They can also misinterpret the causal relationships with their drinking, or example, believing, “I drink a lot because my wi e nags me,” when in act the opposite is true (con ict arises because o the patient’s drinking). Addicted patients in denial requently cannot ully see the ef ects their use has on the lives around them.

■ SUBSTANCE USE AFFECTS DECISION MAKING Cognitive changes occur with chronic drug use, particularly with loss o ability to make decisions and weigh uture consequences against immediate grati cation—this is why addicted patients sometimes ba e us by leaving the hospital against medical advice. Addicted people do not make decisions the way nonaddicted people do. When the neurochemistry o the limbic system is altered in longterm drug use, decisions about drug use are driven by craving rather than by reason. In addition, many addicted people begin using during adolescence, around age 12 to 14. Individuals who rely on drug use as their primary coping mechanism do not learn any urther coping skills that oster maturity. This means that a 46-year-old patient who has been using continuously since adolescence may have the emotional maturity and coping skills o a 13-year-old.

■ DIFFERENTIAL DIAGNOSIS Tolerance re ers to homeostatic adaptations due to the repeated presence o a drug over an extended period. It is de ned by emergence o physical symptoms (a withdrawal syndrome) when the

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■ “I DON’T HAVE A PROBLEM”

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Substance use occurs on a continuum rom sporadic use to abuse to dependence and addiction. Rather than being de ned by requency o use, the hallmark o addiction is continued use despite consequences. Consequences may be social (damaged relationships), nancial (money spent on drugs, or lost pay due to work absence), legal (driving under the in uence or disorderly conduct), or medical (in ections, overdoses, injuries while intoxicated, pancreatitis). In general, “i you’ve had problems because o drinking or using drugs, then you have a problem with alcohol or drugs.” This means that some alcoholic and addicted individuals use episodically, or in a “binge” pattern—not necessarily every day. The natural history o addiction is progressive, with a variable rate: some patients progress rapidly rom abuse to severe addiction; others smolder or years with less severe consequences. Few are able to stop permanently on their own. With each relapse to substance abuse, the addiction usually returns immediately to its worst point and progresses urther. Depending on the substance(s) o choice, there can be a “shotgun ef ect” o end-organ damage involving every organ system. The American Psychiatric Association’s Diagnostic and Statistical Manual o Mental Disorders, 5th Edition (DSM-5) contains specif c criteria or diagnosing mild, moderate, and severe substance use disorders.

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RECOGNIZING ADDICTION

substance is stopped. The body adapts in this way to many prescription medications, such as antihypertensives, SSRIs, and opioid pain medications; this is why clonidine, beta-blockers, and some SSRIs need to be tapered slowly rather than stopped abruptly. Both tolerance and withdrawal are expected in patients with chronic pain on long-term opioid therapy, but neither de nes addiction. That is why substance use disorders (SUDs) are diagnosed based on behaviors and consequences, not just physical tolerance and withdrawal. Pseudoaddiction: Imagine or a moment that a person has chronic or acute pain rom, say, a emoral racture. Imagine that the pain was not adequately treated with the medication prescribed at discharge. What strategies could the person employ to get the pain treated? The person might take larger doses o the prescribed pain medication, re ll it early, leave repeated messages or the prescribing physician, even resort to an emergency department visit or pain medication. She might borrow a ew hydrocodone rom a riend. Based on her behavior, she might correctly be labeled a “drug seeker.” This is pseudoaddiction, when untreated pain motivates a desperate patient to seek relie in ways that resemble addictive behaviors. It can be di cult to unravel whether pain or addiction, or both, are causing the behaviors; thus, pseudoaddiction should always be in the dif erential diagnosis list. Mental illness: Acute intoxication can mimic the symptoms o anxiety, depression, mania, paranoia, psychosis, and even schizophrenia. Drug rebound and withdrawal can also imitate psychiatric conditions. Only a care ul history with strict attention to the timing o onset o psychiatric symptoms and drug use can begin to elucidate the diagnosis. There is a strong association between substance use disorders and major depression, dysthymia, hypomania, social phobia, panic, and generalized anxiety; close to hal o substance users may have some degree o concurrent personality disorder. Sometimes people with mental illness resort to illicit drug use in order to avoid unpleasant psychiatric symptoms; mental illness and drug use can then produce new psychiatric symptoms that result in more drug use. Drugs can precipitate new psychotic breaks that persist a ter intoxication in previously unaf ected individuals. The two can be intimately entwined and uel each other. Dual diagnosis or co-occurring disorder re ers to a coexisting psychiatric diagnosis as well as a substance use disorder. Substance-induced mood disorder re ers to new mood symptoms experienced a ter the onset o substance use. Some sober time may be required to disentangle drug ef ects rom underlying mental illness. Symptoms or diagnosis o mental illness prior to introduction o drugs and alcohol can be a clue. Outcomes are generally poorer or dually diagnosed patients, and once concurrent mental illness is established, addiction and mental illness must be treated concurrently, rather than waiting or the SUD to “clear.” Your patient may never achieve sobriety i the mental illness is not treated. Chaotic social situation: A patient who is homeless or has an abusive or unstable social situation may present with behaviors mimicking addiction, such as missed appointments, multiple admissions (including admissions or pain control), early re lls on medications, multiple phone calls, and the like. The person may meet criteria or problem opioid use or problem prescription drug use based on behaviors that are troubling to health care personnel rather than behaviors driven by addiction.

s

drive would make you increasingly anxious and uncom ortable until nothing in your environment could prevent you rom taking a breath. And with the rst breath you would begin to eel relie , begin to return to “normal.” A ter derangement o multiple brain systems, stopping breathing is what it eels like or an addicted person to stop using. That is why the relapse rate is so high i the disease o addiction is not treated properly.

■ EPIDEMIOLOGY AND RISK FACTORS Excluding nicotine addiction (which in itsel causes 485,000 deaths in this country each year), substance use disorders have a 16% li etime prevalence in the United States. Death rates are 50 to 100 times higher among substance users. Four out o every 10 amilies are af ected by addiction. Given the 50% genetic contribution to the etiology o addiction, an af ected amily member is a power ul risk actor. The 50% environmental contribution has to do with cultural and 2071

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amily norms that value or stigmatize drugs and alcohol, exposure at an early age, and availability o mind-altering substances. We know that perception o drugs and alcohol as dangerous and socially unacceptable is protective against experimentation and development o addiction. Point prevalence is highest among males 15 to 19, but addiction cuts across gender, race, and socioeconomic status. In women, there is a strong association between sexual/physical violence, including childhood sexual abuse, and starting to drink. As a pro ession, physicians have among the highest rates o substance abuse and addiction. Impulsivity and an orientation toward immediate grati cation are risk actors or SUDs. Thus, adolescents are at high risk: they can be impulsive, rebellious, and novelty seeking with poorly developed judgment. Early exposure to substances in adolescence may lead to permanent brain changes; one-third o adolescent drinkers develop alcohol abuse or dependence in adulthood, and the younger the age at rst use, the greater risk o subsequent SUD. Early diagnosis makes treatment more ef ective, so ailing to screen or substance use is like not checking blood sugar in a new diabetic, or not checking or HIV disease with suspicious in ections. It is important to ask adolescents about substance use and to check urine toxicologies to con rm the history. TWELVE-STEP PARTICIPATION SUPPORTS SOBRIETY Alcoholics Anonymous (AA) started in 1935 when two sel proclaimed “hopeless alcoholics”—one o them a physician—came together to help each other stop drinking. They published a guide, ormally titled Alcoholics Anonymous but better known as the “Big Book” in 1939, whereby others could retrace their steps in supporting each other to sobriety. AA is ree and available in nearly every locale, currently with more than 2 million members in 105,000 groups across 182 countries. The only requirement to attend meetings is a desire to stop drinking. The 12 Steps re er to a “higher power,” which some members interpret as God; however, AA is spiritual—not religious—and members may interpret “higher power” as any wisdom stronger than their own. For example, a group o people can be a higher power. AA speci cally re utes any connection to organized religion, and the “Big Book” discusses its compatibility with atheism and agnosticism in Appendix II, “Spiritual Experience.” Many patients are able to stop drinking or using with only 12-Step participation in the absence o pro essional treatment. Statistically, AA with physician visits works as well as pro essional therapy (cognitive behavioral therapy and/or motivational enhancement therapy), but it is impossible to know which patients will respond best to which treatment; thus it is recommended that patients start with pro essional treatment to learn a new bedrock o coping skills, and then continue with li elong 12-Step participation. Un ortunately, patients are unlikely to ollow-up with an AA telephone number provided by physicians; however, putting the patient directly in touch with an AA member while they are in the o ce can be tremendously ef ective. A sponsor is an individual with several years o success ul recovery who can shepherd a new member, or newcomer, through the 12 Steps and be available to the newcomer 24 hours a day, 7 days a week should a crisis or craving emerge. The sponsor serves as a mentor and positive role model, accompanying the newcomer to meetings, and maintaining requent contact between meetings. A newcomer can always ask the group to assign an appropriate sponsor. Physicians can demonstrate support or a patient’s 12-Step “program” by inquiring what step she is working on, whether she has a sponsor, and how much “sober time” she has. It is important or the physician to listen to the patient’s concerns (and complaints) about 12-Step participation, then encourage the patient to continue attending. Because every AA group is autonomous, each group develops its own personality and avor; a patient who does not like one group should

try another. The 12-Step mutual-help model has been modi ed to help compulsive behaviors rom drug use (Narcotics Anonymous, Pills Anonymous, Marijuana Anonymous, Cocaine Anonymous, and others) to compulsive sex to hoarding and cluttering. There are also groups or alcoholics with special interests such as musicians, proessionals, gay and lesbian people, nonsmokers, and various ethnic groups. AA groups or physicians include Caduceus and International Doctors in AA (IDAA). ADDICTION IS A FAMILY DISEASE Codependence describes a loved one’s misguided attempts to protect an addicted or alcoholic individual rom the consequences o his or her consumption o drugs or alcohol. It is a natural instinct to shelter loved ones rom negative consequences, but in the case o addiction, this can be very harm ul by allowing the addiction to continue and progress to greater severity. Unwittingly acting as an accomplice to an addiction is known as enabling. Enabling ranges rom making excuses and explaining away behaviors to bailing an addicted individual out o jail, to providing a place to use drugs or alcohol, to joining in the use o alcohol and drugs. Codependents tend to ocus on helping the addicted person manage short-term crises rather than ocusing on long-term recovery rom drugs and alcohol. The addicted person and the amily may derive some unconscious secondary bene t rom the addictive behavior that makes it di cult to stop (eg, the codependent individuals may be distracted rom addressing their own problems by helping the addicted person instead). Codependents may even ally with the addicted person against physicians or others encouraging treatment and recovery. The stress o codependence, and involvement with an addicted person can be the root o somatic complaints. Thus, drug and alcohol abuse should be part o the amily history obtained o every patient. Just as codependents can have a large role in enabling a person’s addiction, they also can have an important role in recognizing the disease and ushering the patient into treatment. Some addicts will not stop using until they eel harm and perceive that they must stop to survive; thus, the best way to expedite treatment is or codependents to stop sheltering their loved one rom the consequences o their use o alcohol or drugs. The consequences can then move an alcoholic or addicted person toward accepting treatment. When amilies are involved in treatment with the addicted individual, outcomes improve signi cantly. Sometimes, codependents need therapy or treatment to gain perspective be ore they are able to support their addicted amily member toward treatment. Family members learn they only control their own behavior, and quitting their codependent roles can ease their anxiety and may be help ul in in uencing the addicted amily member to seek treatment. “Love with detachment” is a goal or amily members. Pro essional group therapy, with a ocus on codependency, is o ten available to amily members at treatment centers. Al-Anon is a mutual support group or people whose lives have been af ected by another person’s addiction. It is based on the 12 Steps, although its central philosophy is that members should start to ocus on themselves rather than continuing to ocus on their loved one’s addiction. Ala-Teen, Families Anonymous, and Tough Love are other mutual support groups or amilies. PROCESS ADDICTIONS Rather than abusing chemical substances, some people continue certain behaviors—such as overeating, gambling, or high-risk sex—despite disastrous consequences. Many behaviors are classi ed among the spectrum o impulse control disorders, such as trichotillomania (obsessive hair-pulling), kleptomania (decreased ability to overcome impulses to steal unwanted items), intermittent explosive disorder ( ailure to inhibit aggressive impulses that

C H A P T E R 2 5 1 A d d i c t i o n o P r e s c r i p t i o n a n d N o n p r e s c r i p t i o n D r u

The brain changes o addiction set the stage or a chronic, recurring illness requiring long-term ongoing treatment. Just as providers care or chronic diseases like diabetes, hypertension, and asthma, they can help manage and coordinate care or the chronic disease o addiction. The rst step is recognizing and diagnosing, then re erring or treatment, and ollowing up each time you see the patient. Detoxi ying an addicted person in the hospital has no more ef ect on the disease o addiction than treating diabetic ketoacidosis (DKA) af ects the course o diabetes. Both require long-term, ongoing management and treatment. Signi cant research demonstrates that, with proper treatment, addiction has recovery and outcomes nearly identical to the other chronic diseases. Detoxi ication means poison exiting the body—in this case, alcohol or drugs o abuse clearing rom the brain and blood. When a person is physically dependent on substances, detoxi cation can result in symptoms known as withdrawal. Some withdrawal syndromes are exquisitely uncom ortable; others are li e threatening. Withdrawal can be medically supervised, which means symptoms are managed to keep patients as sa e and com ortable as possible during withdrawal. This is only the rst step in what will become li elong treatment. Just as success ully managing a diabetic patient through DKA does not change the course o the disease, a detoxi cation episode will not alter the natural history o addiction unless the patient is treated. Just as the person with diabetes will need ongoing hypoglycemics, statins, and blood sugar monitoring, the person with addiction will need ongoing counseling, group participation (to de eat the isolation o addiction), and urine toxicology monitoring. Long-term management o stressors and re-emergent cravings, even a ter sustained abstinence, is crucial to relapse prevention. I the treatment or diabetes or hypertension is stopped, the symptoms again mani est in ull orce. The same is true or addiction and alcoholism. Treatment means interventions delivered by licensed pro essionals; mutual help re ers to community support groups such as AA, Rational Recovery, and Secular Organizations or Sobriety. Most recovery models employ both treatment and mutual help, engaging patients and their amilies in education and therapy whenever possible. Because multiple brain systems are disrupted with longterm substance abuse (and multiple areas o a patient’s li e are damaged by addiction), multiple modalities are required to strengthen impulse control, overcome learned responses, support decision making, teach new coping skills, and ocus on rewards that compete with substance use. It is clear that skilled, empathic therapy styles achieve better outcomes than con rontational approaches. Many treatment programs also incorporate the use o medications to help maintain sobriety—such medications have a small but measurable bene t and should be routinely of ered to patients (in ormation on such medications is in subsequent chapters). Thus the best treatment programs have specialized physician involvement; without

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physician involvement, programs may not be able to of er medications or diagnose or treat comorbid psychiatric or medical disorders. Abstinence-based means that a treatment program expects abstinence rom all mind-altering substances, not just the patient’s drug o choice; or example, a patient in treatment or alcohol dependence is expected not to use heroin or cocaine; a person in treatment or methamphetamine dependence is expected not to use cannabis or recreational vicodin. A patient is considered to be abstinent and sober when taking medications as prescribed by a physician—including methadone or buprenorphine (suboxone) or relapse prevention; all major 12-Step groups are in agreement. Sobriety (abstaining rom mind-altering chemicals) is the bedrock to recovery, but recovery rom addiction is more than just abstinence. It is learning new honesty and coping skills, and many times involves a spiritual trans ormation that can result in a new citizenship in society. Recovery is not something that is ever complete; it is evolving, never-ending growth. No signi cant outcome advantage has been proven or residential over outpatient treatment. The treatment venue is less important than the duration o engagement in treatment. Some patients, due to the severity o their disease or the chaos o their social situation, may bene t rom more highly structured treatment (residential or partial hospitalization vs outpatient). In general, more intense treatment is of ered during the newly sober period, tapering of to less requently as the patient gains stability and experience. Research shows that a minimum o 3 months o treatment is required or sustained bene t, with continued progress a ter 3 months. It is important or the patient to maintain some continuous connection to mutual help and/or treatment or li e—otherwise relapse can occur even a ter years o abstinence. When do substance users seek treatment? Some addiction experts believe that spiraling consequences and distress related to substance use, compounded by pressure rom amily, riends, and others can catalyze change ollowing a speci c “trigger event,” when an individual realizes that she cannot manage her addiction without help. In many cases, an intervention staged by amily and riends can be help ul in moving a patient toward treatment. It is important to take advantage o such opportunities, when a substance user is ready to accept help; patients can be lost i treatment is not easily available to them.

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are disproportionate to the precipitating stressor), and obsessivecompulsive disorders. However, the compulsive nature o these behaviors is not mutually exclusive with addiction. These behaviors raise dopamine in the limbic system, although much less than substances o abuse, and are repeated in order to decrease anxiety. Some research indicates a shared genetic vulnerability between substance abuse and impulse control disorders. Because process addictions share common threads with substance use disorders, it ollows that some o the same treatments might be use ul. 12-Step groups have been modi ed to address hundreds o dif erent behaviors, rom binge eating (Overeaters Anonymous) to compulsive shopping (Overspenders Anonymous), pornography overuse, Internet overuse, pathological gambling (Gamblers Anonymous), hoarding, pathological cluttering, and many others.

■ MONITORING Patients with chronic disease underreport damaging health behaviors that may re ect poorly on them. For example, patients with diabetes may underreport dietary indiscretion, and patients with congestive heart ailure may underreport their salt intake; thus, it is important to check hemoglobin A1Cs and daily weights to be certain that the medical treatments are working, and to provide an objective measure o compliance with those treatments. Substance use disorders are no exception, and monitoring, usually with urine toxicology screening or breath-alcohol testing, is an important part o addiction treatment. Urine tests or Ethylene Glycol (ETG), an ethanol metabolite, detect alcohol intake during the previous 80 hours. Because relapse is a part o chronic disease, positive toxicology results (meaning the sample was positive or the presence o illicit substances), in concert with the patient’s history, should be addressed with empathy and support, not with con rontational accusation. BRIEF INTERVENTION IMPROVES OUTCOMES Hospitalists have a unique opportunity to help motivate someone toward treatment. The admission provides a “teachable moment,” and, as already mentioned, intervention outcomes are better or physicians who use an empathic approach rather than a con rontational 2073

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one—this means being accepting, not approving o drug use. Overt persuasion results in patients’ working hard to resist the persuasion; they do not want to acknowledge pain ul realities to themselves or others. Motivational interviewing (MI) is an evidence-based process that encourages patients to voice their own reasons or stopping or cutting back. Most substance users have some degree o ambivalence (strong eelings both ways) about continuing their use, and MI is a way to identi y and ampli y the desire to stop using. In its simplest orm, motivational interviewing queries the patients on the bene ts o continuing substance use, the disadvantages o stopping, the disadvantages o continuing, and the advantages o sobriety. Asking nonjudgmentally about all our, without criticizing or blaming, helps patients to articulate their own reasons or quitting and does not create resistance. Another model or brie intervention is the our A’s: ask, advise, assist, arrange. For any substance, including nicotine, the physician asks about length o use and consequences ( amily, job, nancial, legal, health, injuries, blackouts, withdrawal, diminished sel -care, etc) and then gives brie , speci c, personalized advice about the health ef ects o the patient’s use: “As your physician, I must advise you that smoking cigarettes is bad or your liver. Because o your elevated liver unction tests, it is important that you stop smoking now. I you stop smoking cigarettes, the damage may not progress urther.” The physician can assist the patient with a re erral to an addiction medicine specialist, 12-Step groups (such as Nicotine Anonymous), or a treatment center specializing in addictions; sometimes this might include prescriptions or nicotine replacement or other medications. Remember that just giving a phone number to a patient results in poor ollow-up; but putting the person in touch with a 12-Step member or treatment center while in the hospital or o ce can have excellent results. Finally, arrange or patients to ollow-up with primary care to review any action they have taken. Some patients will not be ready to stop using immediately;

physicians must remain patient, empathic, and supportive at every admission when inquiring about substance use. CONCLUSION: ADDICTION IS A TREATABLE BRAIN DISEASE Addiction is a multi actorial chronic brain disease with social and behavioral dimensions. The brain’s limbic system is the seat o the disease, but addiction can result in end-organ damage to every system. The natural history o addiction is generally chronic relapsing-remitting with progression over time. New discoveries in brain imaging, genetics, and neurobiology shed light on the multiple brain systems af ected in addiction. While psychobehavioral treatment remains the cornerstone o treatment, medications to modulate brain unctions involved with cravings are emerging to buttress patients’ recovery. With proper treatment, patients with the disease o addiction have outcomes equivalent to those with other chronic diseases such as asthma, diabetes, and hypertension. The hospitalist physician can have a pivotal role in recognizing disease and directing these patients toward treatment and recovery.

SUGGESTED READINGS Alcoholics Anonymous. www.aa.org. Dupont R. The Self sh Brain: Learning rom Addiction. Center City, MN: Hazelden Publishing; 2000. National Institute on Drug Abuse In ormation or Healthcare Pro essionals. www.drugabuse.gov/NIDAmed/. Ries RK, Fiellin DA, Miller SC, Saitz R. The ASAM Principles o Addiction Medicine, 5th ed. Philadelphia, PA: Wolters Kluwer Health/Lippincott Williams &Wilkins; 2014. Substance Abuse and Mental Health Services Administration (SAMHSA). Searchable database o treatment acilities. www.samhsa.gov.

SECTION 18 Vascular Medicine

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Venous Thromboembolism Prophylaxis or Hospitalized Medical Patients Menaka Pai, MSc, MD, FRCPC James D. Douketis, MD, FRCPC, FACP, FCCP

WHAT IS THE RISK FOR VENOUS THROMBOEMBOLISM (VTE) IN HOSPITALIZED MEDICAL PATIENTS?

■ EPIDEMIOLOGY Venous Thromboembolism (VTE), which comprises deep vein thrombosis (DVT) and pulmonary embolism (PE), is a common cause o morbidity and mortality in hospitalized medical patients. The baseline incidence o asymptomatic VTE in hospitalized medical patients without anticoagulant prophylaxis is 7% to 15%. Linked administrative database studies indicate that 1.7% o hospitalized medical patients develop symptomatic VTE within 3 months o hospitalization. This is lower than in surgical patients, who have a risk o 2% to 3%. However, because o the sheer number o hospitalized medical patients when compared to surgical patients, the burden o illness is high. Approximately 50% to 70% o symptomatic VTE and 70% to 80% o atal PE occur in medical patients, and recent hospitalization or medical illness accounts or 25% o all VTE diagnosed in the community. The quoted risk o 1.7% is also based on the risk in all medical patients, some o whom have less severe illness. In prospective studies assessing medical patients who have at least one major risk actor or VTE such as severe cardiac or respiratory disease and do not receive VTE prophylaxis, the incidence o DVT as detected by venography is approximately 10% to 15%. In the absence o anticoagulant prophylaxis, the incidence o proximal DVT, which is the type o DVT most likely to embolize, is approximately 5% and the incidence o PE is 0.5%. VTE is associated with potentially serious long-term complications, including post-thrombotic syndrome, cardiorespiratory insu ciency, recurrent VTE, and bleeding associated with anticoagulant therapy. VTE is also a common cause o readmission to the hospital, and is associated with increased hospital costs and length o stay.

PRACTICE POINT Risk o thrombosis • Approximately 50% to 70% o symptomatic VTE and 70% to 80% o atal PE occur in medical patients. • Recent hospitalization or medical illness accounts or 25% o all VTE diagnosed in the community. • In prospective studies assessing medical patients who have at least one major risk actor or VTE such as severe cardiac or respiratory disease and do not receive VTE prophylaxis, the incidence o DVT as detected by venography is approximately 10% to 15%.

■ PATHOPHYSIOLOGY Hospitalization or an acute medical illness is independently associated with about an eight old increased risk or VTE. Chart audits have shown that nearly all hospitalized medical patients have at least one VTE risk actor, be it immobility, increased age, cancer (active or occult), or acute medical illness (eg, congestive heart ailure, obstructive lung disease). Certain populations o hospitalized medical patients, such as those in the intensive care unit, have additional risk actors including central venous catheterization; these patients are considered to be at high risk or VTE, even a ter receiving routine prophylaxis (Table 252-1). 2077

P A R T V I C l i n i c a l C o n d i t i o n s i n t h e I n p a t i e n t

Increasing age Immobility (con ined to bed, needing assistance to ambulate) Pregnancy and the puerperium Acute medical illness (eg, congestive heart ailure, obstructive lung disease) Acute ischemic stroke Acute neurologic disease In lammatory bowel disease Cancer (active or occult) Sepsis Previous VTE Prior pelvic radiation Inherited or acquired thrombophilia Myeloproli erative disorders Obesity Medications (eg, chemotherapy, hormonal therapy, selective estrogen receptor modulators, erythropoeisis-stimulating agents) Central venous catheterization (eg, PICC line, internal jugular line)

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TABLE 252-1 Factors that Increase Risk or Venous Thromboembolism in Hospitalized Medical Patients

WHICH HOSPITALIZED MEDICAL PATIENTS NEED VTE PROPHYLAXIS?

■ VTE PROPHYLAXIS IN GENERAL MEDICAL PATIENTS There is no ormal, widely accepted, prospectively validated risk strati cation algorithm to guide VTE prophylaxis in medical patients. As a general guide, medical patients presenting with ischemic stroke, acute exacerbations o chronic heart ailure or chronic obstructive pulmonary disease, acute respiratory ailure, cancer, history o prior VTE, sepsis, acute neurologic disease, or severe in ammatory disease should be given VTE prophylaxis. Immobility is considered a weaker risk actor, and is di cult to clearly de ne. However, patients who cannot ambulate without assistance still merit consideration or prophylaxis. A number o data-derived risk models to predict VTE in medical patients have been proposed, including the Padua prediction score, the IMPROVE risk score, and the Geneva risk score. They include many o the above criteria. A recent meta-analysis has shown that pharmacologic prophylaxis is ef ective in reducing atal PE, symptomatic PE, and symptomatic DVT by more than 50% with no increase in major bleeding compared with placebo in general medical patients. There is no ef ect on all-cause mortality, and the number needed to treat to prevent one symptomatic PE is high (more than 300). However, due to the large number o at-risk hospitalized medical patients, thromboprophylaxis still provides an opportunity to reduce morbidity in a signi cant number o patients. There does not appear to be a dif erence in bleeding rates or VTE rates between low-dose un ractionated heparin (LDUH), low-molecular-weight heparin (LMWH), and ondaparinux. Meta-analyses have suggested that LMWH is superior to LDUH (both twice- and thrice-daily regimens) in high-risk populations, though included studies included studies enrolled heterogeneous groups, and did not always dif erentiate symptomatic and asymptomatic VTE.

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TABLE 252-2 Contraindications to Thromboprophylaxis with Anticoagulants Excessive active bleeding At high risk or bleeding that precludes anticoagulants (eg, brain lesion) Recent serious bleeding (eg, within 1 mo) Coagulopathy (eg, INR >1.5, aPTT >40) Thrombocytopenia (eg, platelets 75 years o age, those with recently reduced mobility). Further, the extended-duration arm in EXCLAIM had an increased risk o major bleeding. ADOPT ound no dif erence between its study arms, though extended-duration prophylaxis increased the risk o major bleeding. MAGELLAN ound that extended-duration prophylaxis reduced the risk o VTE (both symptomatic and asymptomatic), though it again con erred an increased risk o major bleeding. A meta-analysis o these three studies concluded that routine administration o postdischarge VTE prophylaxis is not likely to make a clinically meaning ul impact or hospitalized medical patients, and could cause harm. At this time, extended-duration prophylaxis is not recommended in medical patients. However, all patients should be educated about the signs and symptoms o VTE at the time o discharge and be instructed to seek urgent medical care i thrombosis is suspected.

■ QUALITY IMPROVEMENT INITIATIVES TO OPTIMIZE VTE PROPHYLAXIS A signi cant gap remains between evidence or VTE prophylaxis and clinical practice in hospitalized medical patients. A recent international registry demonstrated that in a population o 15,156 hospitalize medical patients only 50% received any orm o prophylaxis. A multicenter Canadian chart audit determined that 90% o acutely ill medical patients were eligible or some orm o prophylaxis, while only 23% received it. What is rather astonishing is that only 16% o patients received appropriate prophylaxis. Medical patients have repeatedly been shown to have the poorest rates o VTE prophylaxis among all hospitalized patients. Yet since 1998, the American College o Chest Physicians has given anticoagulant prophylaxis in at-risk hospitalized medical patients a Grade 1A recommendation (their highest level). The American College o Physicians also strongly advocates or risk assessment and anticoagulant prophylaxis in this group. Why is VTE prophylaxis underused in hospitalized medical patients? It is likely because medical patients are more heterogeneous than their counterparts on surgical wards. Their need or prophylaxis is not driven by a standardized type o surgery, but by their underlying diseases, their mobility status, and their reason or hospitalization. Health care providers may be unclear about the indications and contraindications or anticoagulant prophylaxis in a given patient. Many organizations have also identi ed VTE as a major patient sa ety concern, including the US Department o Health and Human Services, the World Health Organization, the World Alliance or Patient Sa ety, and the International Alliance o Patients’ Organizations. VTE prophylaxis has also been highlighted as an important eature o hospital accreditation commissions and quality improvement 2080

campaigns worldwide. Evidence supports a multicomponent strategy to optimize VTE prophylaxis in hospitalized medical patients, including ormal hospital policy, standardized preprinted order sets, computer decision support systems, electronic and human alerts, and periodic audit and eedback. Hospitalists are in an ideal position to champion appropriate VTE prophylaxis in hospitalized medical patients, at a local, national, and international level.

SUGGESTED READINGS Alikhan R, Cohen AT. A sa ety analysis o thromboprophylaxis in acute medical illness. Thromb Haemost. 2003;89:590-591. CLOTS Trials Collaboration, Dennis M, Sandercock PA, Reid J, et al. Ef ectiveness o thigh-length graduated compression stockings to reduce the risk o deep vein thrombosis a ter stroke (CLOTS trial 1): a multicentre, randomised controlled trial. Lancet. 2009;373:1958-1965. Cohen AT, Tapson VF, Bergmann JF, et al. Venous thromboembolism risk and prophylaxis in the acute hospital care setting (ENDORSE study): a multinational cross-sectional study. Lancet. 2008;371:387-394. Cohen AT, Spiro TE, Büller HR, et al. Rivaroxaban or thromboprophylaxis in acutely ill medical patients. N Engl J Med. 2013;368(6):513-523. Cook D, Crowther M, Meade M, et al. Deep venous thrombosis in medical-surgical critically ill patients: prevalence, incidence, and risk actors. Crit Care Med. 2005;33:1565-1571. Douketis J, Cook D, Meade M, et al. Prophylaxis against deep vein thrombosis in critically ill patients with severe renal insu ciency with the low-molecular-weight heparin dalteparin: an assessment o sa ety and pharmacodynamics: the DIRECT Study. Arch Intern Med. 2008;168:1805-1812. Goldhaber SZ, Leizorovicz A, Kakkar AK, et al. Apixaban versus enoxaparin or thromboprophylaxis in medically ill patients. N Engl J Med. 2011;365(23):2167. Kahn SR, Lim W, Dunn AS, et al. Prevention of VTE in nonsurgical patients: antithrombotic therapy and prevention of thrombosis, 9th ed: American College o Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141(2 Suppl):e195S-e226S. Kakkar AK, Levine MN, Kadziola Z, et al. Low molecular weight heparin, therapy with dalteparin, and survival in advanced cancer: the Fragmin Advanced Malignancy Outcome Study (FAMOUS). J Clin Oncol. 2004;22:1944-1948. Khorana AA, Kuderer NM, Culakova E, Lyman GH, Francis CW. Development and validation o a predictive model or chemotherapyassociated thrombosis. Blood. 2008;111(10):4902. MacDougall DA, Feliu AU, Boccuzzi SJ, Lin J. Economic burden o deep-vein thrombosis, pulmonary embolism, and postthrombotic syndrome. Am J Health Syst Pharm. 2006;63(20 Suppl 6):S5-S15. PROTECT Investigators or the Canadian Critical Care Trials Group and the Australian and New Zealand Intensive Care Society Clinical Trials Group, Cook D, Meade M, et al. Dalteparin versus un ractionated heparin in critically ill patients. N Engl J Med. 2011;364(14):1305. Samama MM, Cohen AT, Darmon JY, et al. A comparison o enoxaparin with placebo or the prevention o venous thromboembolism in acutely ill medical patients. N Engl J Med. 1999;341: 793-800. Turpie AG. Extended duration o thromboprophylaxis in acutely ill medical patients: optimizing therapy? J Thromb Haemost. 2007; 5:5-11.

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Diagnosis and Treatment of Venous Thromboembolism Kerstin Hogg, MD, MBChB, MSc Lori-Ann Linkins, MD, MSc Clive Kearon, MB, MRCPI, FRCPC, PhD

Key Clinical Questions 1

Why are objective tests needed to diagnose venous thromboembolism (VTE)?

2

Which tests can be used to diagnose a irst deep vein thrombosis (DVT)?

3

Which tests can be used to diagnose recurrent DVT?

4

Which tests can be used to diagnose pulmonary embolism (PE)?

5

Which patients with VTE can be treated as outpatients?

6

What is the treatment or acute VTE, DVT, and/or PE?

7

What is the role o thrombolytic therapy in the treatment o PE?

8

How are patients with acute VTE and bleeding managed?

9

How is the duration o treatment o VTE determined?

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Should I per orm a thrombophilic workup?

11

What is the risk o bleeding associated with long-term anticoagulant therapy?

INTRODUCTION In 800 BC, Susruta, an Indian healer wrote about a patient with “a swollen and pain ul leg, which was di cult to treat.” Centuries later, Virchow, a Prussian physician, coined the term “embolism” a ter discovering the relationship between a blood clot that ormed within a blood vessel (thrombus), and a blood clot that breaks loose and travels through the bloodstream to occlude the pulmonary vessels (embolus). The concept o venous thromboembolism was born rom these early descriptions and today it remains one o the most important health problems in Europe and North America and is the third leading cause o vascular death a ter myocardial in arction and stroke. The risk o venous thromboembolism (VTE) increases by approximately two old per decade o age, rising rom an annual incidence o 30/100,000 at 40 years o age, to 90/100,000 at 60 years, and 260/100,000 at 80 years. Approximately hal o patients with untreated, symptomatic proximal deep vein thrombosis (DVT) will develop symptomatic pulmonary embolism (PE), and about 10% o symptomatic PE are atal within an hour o onset. Le t untreated, one-third o patients with initially non atal PE will have a atal recurrence, generally within a ew weeks o the original event. Even with optimal treatment, about 5% o patients with PE will die rom atal PE, and about 25% with proximal DVT will develop post-thrombotic syndrome, a chronic condition that is debilitating or patients. Venous thromboembolism is now recognized as the leading cause o preventable death in hospitalized patients. Almost all hospitalized patients have one or more risk actors or VTE and 40% will have three or more risk actors. VTE prophylaxis (addressed in Chapters 56, 65, and 252) orms the cornerstone or preventing these deaths. In addition, although 75% o venous thromboembolic events are diagnosed in the outpatient setting, about hal o all episodes o VTE are associated with recent surgery or hospitalization. These ndings stress the importance o having a low threshold to per orm diagnostic testing in patients who present with signs and symptoms compatible with VTE within 3 months o hospitalization. There ore, VTE is both an acute and a chronic disease that causes substantial patient morbidity and mortality, and it is a major burden on the health care system. Costs or VTE include not only the expense o initial diagnosis and treatment, but also the cost o the complications o VTE (ie, post-thrombotic syndrome, venous ulceration, chronic thromboembolic pulmonary hypertension, recurrent VTE) and its treatment (ie, bleeding). It is currently estimated that VTE costs the US health care system $1.5 billion/y.

■ NOMENCLATURE Proximal DVT is de ned as a DVT that involves the popliteal vein or more proximal veins o the leg (most also involve the cal veins). Distal DVT is de ned as a DVT that is con ned to the cal veins.

PRACTICE POINT The natural history of VTE • DVT typically starts in the cal (distal) veins • Two-thirds o symptomatic DVT are located in the proximal veins

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Virchow’s triad or the pathogenesis o thrombosis is as relevant today as it was when it was originally described in the 18th century: venous stasis, vessel wall damage, and hypercoagulability. A summary o common risk actors or VTE is given in Table 253-1.

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Deep-vein thrombosis is more likely to occur in the paralyzed leg ollowing stroke, and in the le t leg during pregnancy because o extrinsic compression o the le t iliac vein by the pregnant uterus and the right common iliac artery.

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■ VENOUS STASIS

■ VESSEL WALL DAMAGE Manipulation during surgery (eg, hip replacement), iatrogenic injury, and use o indwelling venous catheters all markedly increase the risk o DVT.

TABLE 253-1 Risk Factors for Venous Thromboembolism (VTE) Patient factors Age over 40. Previous VTE. Inherited hypercoagulable states. Underlying condition and acquired factors Hospitalization Acute medical illness (eg, congestive heart ailure, COPD exacerbation) Surgery Surgery requiring general anaesthesia >30 min lower limb orthopedic surgery major trauma Nursing home Prolonged immobility (eg, limited ambulation or > 48 h within past 30 d) Paralysis lower limb injuries Obesity Pregnancy, puerperium Estrogen therapy (eg, oral contraceptive, hormone replacement therapy) Malignancy Chemotherapy Central vein catheterization, transvenous pacemaker In lammatory bowel disease Nephrotic syndrome Systemic lupus erythematosus Antiphospholipid antibodies Heparin-induced thrombocytopenia

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■ HYPERCOAGULABILITY Inherited or acquired changes in the balance o naturally occurring coagulation and brinolytic actors and their inhibitors predispose to thrombosis. The inherited hypercoagulable conditions that are considered strong risk actors or thrombosis; antithrombin de ciency, protein C de ciency, and protein S de ciency, are rare (3 d or major surgery within the previous 12 wk requiring general or regional anesthesia Localized tenderness along the distribution o the deep venous system Entire leg swollen Cal swelling 3 cm >asymptomatic side (measured 10 cm below tibial tuberosity) Pitting edema con ined to the symptomatic leg Collateral super icial veins (nonvaricose) Previously documented deep-vein thrombosis Alternative diagnosis as likely or greater than that o DVT Total points (pretest probability for DVT) Score >2: High Score 1-2: Moderate Score ≤0: Low

Points 1

e

■ IMAGING TESTS FOR DVT

TABLE 253-2 The Wells Clinical Prediction Rule for DVT

n

For the reasons outlined above, clinical assessment alone is an unreliable test or diagnosing DVT. However, clinical prediction rules have been developed that can help to strati y patients as having a low (5% prevalence), moderate (25% prevalence), or high (60% prevalence) probability o DVT (Table 253-2). Hospitalized patients are less likely to have a low probability score. Classi cation o pretest probability is help ul when used in combination with other diagnostic tests (Figure 253-1). I there is a high risk clinical suspicion or DVT (or PE) and patients are not at high risk or bleeding, it is recommended that anticoagulant therapy is started be ore diagnostic testing is per ormed. Treatment can be de erred i diagnostic testing will be per ormed within 4 hours in patients with a moderate and within 24 hours in patients with a low clinical suspicion or DVT (or PE).

o

■ CLINICAL ASSESSMENT

h r o m o m

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Appro ac h to the Patie nt with S us pe c te d Firs t Ac ute DVT

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Ultrasonography is the rst-line imaging test used to diagnose or exclude DVT. When pressure is applied to the proximal veins with

Data rom Wells PS, Anderson DR, Rodger M, et al. Evaluation o D-dimer in the diagnosis o suspected deep-vein thrombosis. N Engl J Med. 2003;349:1227-1235.

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Compression venous ultrasound

Clinica l proba bility of DVT

High or mode ra te

Low

Compre s s ion ultra s ound

D-dime r te s ting

P os itive

Tre a t for DVT

D-dime r pos itive or not a va ila ble

Ne ga tive

If clinica l proba bility is low, DVT is e xclude d.

D-dime r ne ga tive *

DVT e xclude d

If clinica l proba bility is high or mode ra te , re pe a t ultra s ound in 7 d.

P os itive

Ne ga tive

Tre a t for DVT

DVT e xclude d

Figure 253 1 Approach to the patient with suspected irst acute DVT. *I D-dimer assay has a sensitivity o greater than or equal to 85% o proximal veins. 2083

P A R T V I C l i n i c a l C o n d i t i o n s i n t h e I n p a t i

• • • • •

Operator dependent in the cal veins Limbs with casts that cannot be removed Morbid obesity Massive edema Isolated pelvic DVT harder to detect

PRACTICE POINT

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an ultrasound probe, the veins should ully compress. I they do not, acute or chronic DVT is present. In symptomatic patients, when the ultrasound probe is applied to the proximal veins, the sensitivity o ultrasound or proximal DVT is 97% and the speci city is 94% when compared with venography ( or both inpatients and outpatients). The sensitivity and speci city o compression ultrasound is lower in the cal veins, and the clinical signi cance o isolated cal vein thrombosis is controversial. For these reasons, many centers do not examine the cal veins with ultrasound; instead, i the initial assessment (eg, low clinical suspicion and negative ultrasound o the proximal veins) cannot exclude the presence o DVT, a ollow-up ultrasound o the proximal veins is done a ter a week to exclude the possibility o cal vein thrombosis with early extension into the proximal veins. I whole leg ultrasound is per ormed and is negative, repeat ultrasound scanning is not necessary. Compression venous ultrasound is requently combined with assessment o Doppler ow; however, change in Doppler ow alone is not a sensitive or speci c test or DVT. Limitations o ultrasound include the actors listed below.

Do not waste time and money by ordering a D-dimer or the ollowing patients: • Postoperative inpatients. • Other patients with severe systemic illness that will markedly increase D-dimer levels. • High clinical suspicion or DVT or PE. Results are very unlikely to be negative and, i they are negative, the post-test probability is still too high or VTE to be excluded. A positive result is unhelp ul.

Clinical prediction rules or diagnosing recurrent DVT are less well developed and validated than or a rst episode o DVT and they have not been widely used.

■ IMAGING TESTS FOR RECURRENT DVT Venography As with rst acute DVT, this method is considered the re erence standard test or recurrent DVT. However, veins previously af ected by DVT may not ll with contrast dye, resulting in nondiagnostic ndings. Compression venous ultrasound In patients with a recent ultrasound that demonstrated (1) limited extent o the previous DVT or (2) complete resolution o the previous DVT, the presence a new noncompressible segment o the proximal veins (eg, popliteal or common emoral vein) on ultrasound examination is diagnostic or recurrent DVT. However, it is important to remember that 50% o patients with f rst acute DVT will still have incomplete compressibility on ultrasound examination 1 year a ter diagnosis despite adequate anticoagulant therapy. Consequently, without clear evidence o a new noncompressible segment, it can be di cult to tell the dif erence between residual chronic DVT and new acute DVT. It can be use ul, there ore, to per orm an ultrasound when the decision is taken to stop anticoagulation in a patient who initially had an extensive DVT. This acts as a baseline scan to which uture scans can be compared. I a proximal US is abnormal but there is no new noncompressible segment, it has been proposed that an increase in residual vein diameter o greater than 4 mm (when a vein is compressed with an ultrasound probe) is diagnostic or recurrence. However, a recent ultrasound (prior to the episode o suspected recurrence) is required to make this comparison, and there is evidence that the reproducibility o the residual diameter measurement is only moderate. Other ultrasound eatures such as Doppler ow and thrombus echogenicity have not been validated as reliable methods or diagnosing recurrent DVT.

D dimer blood testing

D dimer blood testing

D-dimer is ormed when cross-linked brin is broken down by plasmin. Normal levels can help to exclude DVT, but elevated D-dimer levels are common with other conditions (eg, malignancy, disseminated intravascular coagulation, acute in ection, normal pregnancy, renal disease, cardiovascular disease). D-dimer levels are also elevated a ter surgery and may take up to 50 days to return to baseline, depending on the type o surgery. Consequently, a positive D-dimer is NEVER diagnostic or DVT! A negative D-dimer can still be used to exclude DVT in a hospitalized patient with a low clinical probability or DVT, but negative results in this patient population are so uncommon (3 days or major surgery within the previous 12 weeks requiring general or regional anesthesia, entire leg edema, cal swelling 3 cm greater than the asymptomatic side (measured 10 cm below tibial tuberosity) and pitting edema con ned to the symptomatic leg, but he also has an alternative diagnosis or his symptoms that is at least as likely as DVT (ie, postoperative edema), which subtracted 2 points. Diagnostic testing: For most outpatients with suspected DVT, calculation o pretest probability (eg, Wells score) ollowed by per ormance o a D-dimer is a good initial approach to diagnosing/excluding DVT. In this case, a D-dimer is very unlikely to be negative given that this patient recently underwent major surgery. As a D-dimer is only help ul when it is negative, it is not requested. A compression ultrasound should be ordered to check or DVT.

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Appro ac h to the Patie nt with S us pe c te d Re c urre nt DVT in the S ame Le g

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Compre s s ion ultra s ound of proxima l ve ins

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DVT e xclude d

Re pe a t ultra s ound in 5-7 d

Re ce nt ultra s ound a va ila ble for compa ris on?

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Abnorma l

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Ne w noncompre s s ible s e gme nt?

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Re pe a t ultra s ound a t 2 a nd 7 d OR ve nogra phy

Tre a t DVT

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YES

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NO

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NO

Re pe a t ultra s ound a t 2 a nd 7 d OR ve nogra phy

Re pe a t ultra s ound a t 2 a nd 7 d OR ve nogra phy OR Tre a t

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P os itive

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D-dime r

Figure 253 2 Approach to the patient with suspected recurrent DVTin the same leg. *I D-dimer assay has a sensitivity o greater than or equal to 85%.

Diagnostic testing in patients with a history o DVT: This case would become signi cantly more di cult i this patient had a history o a DVT in the same leg. The decision not to order a D-dimer would remain unchanged and the patient would still have a compression ultrasound study. However, i the ultrasound was abnormal, his clinicians would also want to try to nd a previous ultrasound report which described the extent o his previous DVT. I he was documented to have complete resolution o his previous thrombus, the nding o any noncompressible segments on the current ultrasound examination would be interpreted as representing new acute DVT. I he had incomplete resolution o his previous thrombus, and the current examination showed noncompressibility in a previously unaf ected segment, he has a new acute DVT (eg, his previous DVT extended up to the mid emoral vein, but today’s examination shows incompressibility o the common emoral vein). I today’s ultrasound examination shows incompressibility

in the same segments as his previous DVT, his clinicians cannot be certain that the ndings represent new acute DVT. They have three choices in this situation: (1) Not to treat, but to repeat the ultrasound at 2 and 7 days (to look or clear evidence o progression which would indicate acute DVT), (2) arrange or a venogram. or (3) treat the patient as an acute DVT or 3 months.

CASE 253-2 A 72-year-old woman has been in hospital or 4 days with pneumonia. She is a ebrile and her cough is no longer productive o purulent sputum, but she continues to be tachypneic and hypoxic. The right lower lobe in ltrate seen on her chest x-ray on admission has not signi cantly changed. Her white blood cell count is slowly decreasing, but she continues to have anemia and

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DOES THIS PATIENT HAVE PE? The commonest symptoms o PE are shortness o breath and atigue. Patients with PE may also present with pleuritic chest pain, palpitations, hemoptysis, and syncope. Signs o PE include tachycardia, tachypnea, accentuated pulmonic heart sound, and S1Q3T3 and evidence o right heart strain on ECG. As with DVT, clinical signs and symptoms are nonspeci c, and objective diagnostic testing must always be per ormed when PE is suspected.

P A R T V I C l i n i c a l C o g

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mild thrombocytosis. All blood cultures have been negative. Her creatinine is elevated due to chronic renal insu ciency. An ECG shows sinus tachycardia. On physical examination, her oxygen saturation is 91% on room air, respiratory rate 25, BP 120/85 mm Hg and heart rate 100 beats/min. Her heart sounds are normal, but she has bronchial breath sounds at her right base on auscultation. She has mild bilateral pedal edema, but denies any tenderness on palpation o her legs. The internal medicine resident looking a ter her is concerned about DVT/PE and orders bilateral leg ultrasounds. The ultrasounds are reportedly negative. What is this patient’s risk for VTE? Has PE been excluded by the negative leg ultrasounds? What are the appropriate investigations for PE?

■ CLINICAL ASSESSMENT As with suspected DVT, clinical assessment can be used in combination with other tests to diagnose PE (Table 253-3).

Pulmonary angiography This method is the re erence standard test or diagnosing PE. However, it suf ers rom the same limitations as venography and it is now very rarely used.

TABLE 253-3 The Wells Clinical Prediction Rule for PE Points 3.0

3.0 1.5 1.5 1.5 1.0 1.0

Data rom Wells PS, Anderson DR, Rodger M, et al. Derivation o a simple clinical model to categorize patients probability o pulmonary-embolism: increasing the models utility with the SimpliRED D-dimer. Thromb Haemost. 2000;83:416-420.

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• •

Computed tomographic pulmonary angiography (CTPA) delivers a relatively high dose o radiation to breast tissue which increases the risk o breast cancer. It should be avoided when possible, and particularly in women less than 50 years o age. One CTPA is equivalent to 100 chest x-rays with respect to radiation!

Computed tomographic pulmonary angiography CTPA Computed tomographic pulmonary angiography (also known as spiral or helical CT) is the current rst-line imaging test or PE. Thrombus in the pulmonary arteries is outlined by radiologic contrast. CTPA has the additional major advantage o detecting alternate causes or symptoms in about one-third o patients with suspected PE (eg, pneumonia, lung mass). Less than 2% o patients with a negative CTPA who are not treated with anticoagulant therapy will return with symptomatic VTE during 3 months o ollow-up. Computed tomographic pulmonary angiography has been shown to have a sensitivity o 83% and a speci city o 96% or PE. However, accuracy varies according to the size o the largest pulmonary artery involved. The probability that an intraluminal lling de ect is due to a PE has been reported as 97% or de ects in the main or lobar artery, 68% or segmental arteries, and 25% or subsegmental arteries (which means that as many as 75% o abnormalities seen in subsegmental arteries are not due to PE). Accuracy o CTPA is also in uenced by clinical assessment o PE; the higher the clinical probability o PE, the more likely the de ect that is seen on CTPA is actually due to PE (Table 253-4). Limitations include the actors listed below. • Requires use o contrast dye • Exposure to radiation • Subject to technical di culties (approximately 6% o CTPA are

■ IMAGING TESTS FOR PE

Clinical signs and symptoms o deep vein thrombosis (minimum o leg swelling and pain with palpation o the deep veins) An alternative diagnosis is less likely than pulmonary embolism Heart rate > 100 beats/min Immobilization or surgery in the previous 4 wk Previous deep vein thrombosis/pulmonary embolism Hemoptysis Malignancy (treatment ongoing or within previous 6 mo or palliative) Total points (pretest probability for PE): Score ≤4: PE unlikely or low Score >4: PE likely (Moderate i 4.5-6, and High i >6)

PRACTICE POINT

nondiagnostic) • Expense Ventilation perfusion lung scanning V/Q This was the rst-line test used to diagnose PE be ore the advent o CTPA, and V/Q scanning is still used, particularly when CTPA is contraindicated (ie, patients with renal ailure, young women due to a concern about breast cancer induced by radiation exposure). Per usion de ects are nonspeci c; only about 33% o patients with per usion de ects have PE. The probability that a per usion de ect is due to PE increases with the size and number o de ects, and i they are mismatched. A mismatch re ers to a per usion de ect that is not associated with a corresponding de ect on the ventilation scan. The V/Q scan probability o PE should be matched with the clinical probability o PE. A high probability lung scan can diagnose PE in patients with moderate or high clinical probability, and a low probability lung scan can exclude PE in a patient with low clinical probability

TABLE 253-4 Interpretation of Findings on CTPA Location o Pulmonary Artery De ect on CTPA Lobar or larger Segmental Segmental Subsegmental

Clinical Probability o PE Any Moderate or high Low Any

Interpretation Very likely PE Likely PE Less certain PE Nondiagnostic

C H R 2 5 3 D i a g n o i s a n d T r e a t m e n t o V e n o u s e

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In many hospitals, three-dimensional SPECT (single-photon emission CT) has replaced planar V/Q scanning. Unlike V/Q, there are no standardized criteria or reporting SPECT. SPECT scans are less likely to be reported as nondiagnostic, with the majority o scans reporting PE present or absent. As yet, there are no large diagnostic studies reporting on the sa ety o diagnosing and excluding PE with SPECT.

T

■ SPECT

This patient’s risk o PE: Hospitalization with acute in ection is a strong risk actor or VTE. In addition, this patient is over age 40 and has been largely bed-bound while in hospital. Hypoxia that is more severe than expected rom the chest x-ray ndings should raise suspicion o PE. Diagnostic Testing: PE has not been excluded. I her leg ultrasounds had been positive or DVT, urther investigations or PE would not be necessary because it would not change her management (ie, the anticoagulant treatment or DVT and PE is the same). However, in this case, proximal DVT has been excluded by negative ultrasounds, but PE has not been excluded.

h

• Large proportion o nondiagnostic scans. • Inability to identi y alternative causes or symptoms.

CASE 253-2 (continued)

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o PE. Lung scan ndings are highly age dependent with a relatively high proportion o normal scans in younger patients, including pregnant women, and a low proportion in those with other acute and chronic cardiorespiratory conditions (Table 253-5). Limitations include the actors listed below:

I initial testing is nondiagnostic (eg, ventilation-per usion scan), there is still a substantial chance that your patient could have a PE and urther investigations are required. One approach to management o such patients is to per orm ultrasonography and withhold anticoagulation i there is no DVT o the proximal veins. Ultrasonography o the proximal veins is then repeated a ter 1 and 2 weeks to exclude evolving VTE. See algorithm Figure 253-3.

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What if the tests I ordered to exclude PE were nondiagnostic?

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Interpretation Very likely PE Nondiagnostic Nondiagnostic Unlikely PE PE excluded

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Clinical Probability o PE Moderate to high Low Moderate to high Low Any

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Mismatched Per usion De ects on V/Q Scanning ≥1 segmental ≥1 segmental ≥1 subsegmental ≥1 subsegmental None

As with suspected DVT, a negative D-dimer result can exclude PE (on its own, i it is a very sensitive assay or in combination with other tests, i it is less sensitive) (Figure 253-3).

A

TABLE 253-5 Interpretation of Findings on V/Q

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D dimer blood testing

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Appro ac h to the Patie nt with S us pe c te d Firs t Ac ute PE

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Clinica l proba bility of P E

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CTP A or VQ (cons ide r a ge & CrCl)

D-dime r te s ting

P os itive

Ne ga tive

Tre a t for P E

P E e xclude d

Nondia gnos tic

D-dime r pos itive or not a va ila ble

Cons ide r the following: • Bila te ra l le g ultra s ounds (re pe a te d on da y 7 a nd 10) • If CTP A wa s the initia l te s t, do a VQ (or vice ve rs a ) • Re pe a t CTP A in 24 h • P ulmona ry a ngiogra phy

P os itive

Ne ga tive

Tre a t for P E

P E e xclude d

D-dime r ne ga tive

P E e xclude d

Figure 253 3 Approach to the patient with suspected irst acute PE. I D-dimer assay has a sensitivity o greater than or equal to 85%.

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P A R T

Currently, CTPA is the most common rst-line imaging test used to diagnose PE. However, this woman is known to have chronic renal insu ciency so this test may not be appropriate. A reasonable alternative is a V/Q scan, especially i she had a normal CXR.

V I C l i n

The oundation o treatment o VTE is anticoagulant therapy. The objectives o anticoagulant therapy are: (1) to prevent extension and potentially atal embolization o the initial thrombus and (2) to prevent recurrent VTE.

■ TRIAGE AND HOSPITAL ADMISSION Patients who are hemodynamically stable with a low bleeding risk and normal renal unction, and who are likely to be compliant with anticoagulant therapy, can be sa ely treated as outpatients. Patients with DVT and severe intractable pain or severe swelling and poor leg per usion should be admitted to hospital or initiation o anticoagulant treatment, and assessment o the need or catheterdirected thrombolysis. Patients with PE and severe symptoms or abnormal vital signs should be admitted to the hospital, and those with signs o hemodynamic compromise (eg, systolic blood pressure