Ferri’s Practical Guide: Fast Facts for Patient Care [9th Edition] 145574459X, 9781455744596, 9781455744589

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Fast Facts for Patient Care

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Ferri's Practical Guide

Fast Facts for Patient Care

Ninth Edition

FRED F. FERRI, MD, FACP � � BROWN � Alpert Medical School Clinical Professor

Alpert Medical School at Brown University Providence, Rhode Island

Author contact for comments about the book: fred_ferri@brown. edu

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ELSEVIER MOSBY

1 600 John F. Kennedy Blvd. Ste 1 800 Philadelphia, PA 1 9 1 03-2899 FERR I ' S PRACTICAL GUI DE: FAST FACTS FOR PATIENT CARE

ISBN:978- 1 -4557-4459-6

Copyright© 2014 by Mosby, an imprint of Elsevier Inc. Copyright© 2011, 2007, 2004, 2001, 1998, 1995, 1991, 1987 by Mosby, Inc., an affiliate of Elsevier Inc. All rights reserved. No part of this publi cation may be reprod uced or transm itted in any form or by any means, electronic or mechan ical, including photocopyi ng, record ing, or any information storage and retrieval system , without perm ission in writi ng from the publisher. Details on how to seek perm ission, further information about the Publ isher's perm issions policies and our arrangem ents with organiza­ tions such as the Copyright Clearance Center and the Copyright Licensing Agency, can be found at our website : www.elsevier.com/permissions. This book and the individual contributions contai ned in it are protected under copyright by the Pub­ lisher [other than as may be noted herein).

Notices Knowledge and best practice in this field are constantly changing. As new research and experi­ ence broaden our understanding, cha nges in research methods, professional practices, or medi­ cal treatment may become necessary. Practitioners and researchers must always rely on their own experience and knowl edge in eval uating and using any information , methods, compounds, or experiments described herein. In using such information or methods they should be mi ndful of their own safety and the safety of others, including parties for whom they have a professional respon sibil ity. With respect to any drug or pharmaceutical prod ucts identified , readers are advised to check the most current information provided [i) on proced ures featured or [ii) by the manufacturer of each product to be ad ministered, to verify the recom mended dose or formula, the method and duration of administration, and contraindicati ons. It is the respon sibil ity of practitioners, rely­ ing on their own experience and knowledge of their patients, to make diagnoses , to determine dosages and the best treatment for each individual patient, and to take all appropriate safety precautions. To the fu llest extent of the law, neither the Publ isher nor the authors, contributors, or editors , assume any liabil ity for any inj ury and/or damage to persons or property as a mat­ ter of products liabil ity, negl igence or otherwise, or from any use or operation of any methods, prod ucts, instructi ons, or ideas contai ned in the material here in.

library of Congress Cataloging-in-Publication Data Ferri, Fred F., author. [Practical guide to the care of the medical patient] Ferri's practical guide : fast facts for patient care I Fred F. Ferri. -- Ninth edition. p. ; em. Practical guide Preceded by Practical guide to the care of the medical patient I Fred F. Ferri. 8th ed. c20 1 1 . Incl udes bibl iographical references and index. ISBN 978- 1 -4557-4459-6 [pbk.) I. Title. I I . Title: Practical guide . [DNLM: 1 . Clin ical Medici ne--Handbooks. 2. Clin ical Laboratory Tech niq ues--Handbooks. 3. Diagnos is, Differential-Ha ndbooks. WB 39] RC55 20 1 3042887 6 1 6--dc23

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T h e a ut h o r w i s h es to a c k n ow l e dge t h e fol l ow i n g physi c i a n s w h o h ave c ontri b uted to this book and to several editions of Ferri 's Clinical Advisor.

Tanya Ali, MD

Mark J. Fagan, MD

Clinical Assistant Professor of

Director

Medicine

Medical Primary Care Unit

Department of Medicine

Rhode Island Hospital

Alpert Medical School

Professor of Medicine

Brown University

Alpert Medical School

Providence, Rhode Island

Brown University

Mel L. Anderson, MD, FACP

Providence, Rhode Island

Assistant Professor of Medicine

Timothy W. Farrell, MD

University of Colorado School of

Clinical Assistant Professor Department of Family Medicine

Medicine Denver Veterans Affairs Medical Center

Alpert Medical School

Denver, Colorado

Brown University

Michelle Stozek Anvar, MD

Providence, Rhode Island

Assistant Professor (Clinical)

Glenn G. Fort, MD, MPH, FACP, FIDSA

Alpert Medical School

Clinical Associate Professor of Medicine

Brown University

Alpert Medical School

Providence, Rhode Island Sudeep Kaur Aulakh, MD, CM, FRCPC

Assistant Professor of Medicine Tufts University School of Medicine Baystate Medical Center Springfield, Massachusetts Lynn Bowlby, MD, FACP

Medical Director Duke Outpatient Clinic Duke Internal Medicine Residency Program Durham, North Carolina Gaurav Choudhary, MD

Assistant Professor of Medicine Alpert Medical School Brown University Providence, Rhode Island

Brown University Chief Infectious Diseases Our Lady of Fatima Hospital North Providence, Rhode Island Paul F. George, MD

Assistant Professor Department of Family Medicine Alpert Medical School Brown University Providence, Rhode Island Sajeev H anda, MD

Director Division of Hospitalist Medicine Rhode Island Hospital Clinical Assistant Professor of Medicine Alpert Medical School

Alexandra Degenhardt, MD

Brown University

Director

Providence, Rhode Island

Multiple Sclerosis Center New York Methodist Hospital Brooklyn, New York

Taylor Harrison, MD

Assistant Professor of Neurology Department of Neurology

Joseph A. Diaz, MD

Emory University

Associate Professor of Medicine

Atlanta, Georgia

Division of General Internal Medicine Memorial Hospital of Rhode Island Alpert Medical School Brown University Providence, Rhode Island

Jennifer Jeremiah, MD

Clinical Associate Professor of Medicine Alpert Medical School Brown University Providence, Rhode Island

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v

vi

Contributors

Powel H. Kazanjian, MD

Joanne M. Silvia, MD

Professor and Chief

Clinical Assistant Professor

Division of Infectious Disease

Department of Family Medicine

Director of H IV Program

Alpert Medical School

University of Michigan Medical Center

Brown University

Professor of Internal Medicine

Providence, Rhode Island

University of Michigan Medical School Ann Arbor, Michigan

Dominick Tammaro, MD

Associate Director

Kelly A. McGarry, MD

Categorical Internal Medicine Residency

Program Director

Co-Director

General Internal Medicine Residency

Medicine-Pediatrics Residency

Program

Division of General Internal Medicine

Rhode Island Hospital

Rhode Island Hospital

Associate Professor of Medicine

Associate Professor of Medicine

Alpert Medical School

Alpert Medical School

Brown University

Brown University

Providence, Rhode Island

Providence, Rhode Island

Lynn McNicol!, MD

Iris Tong, MD

Assistant Professor of Medicine

Assistant Professor

Alpert Medical School

Department of Medicine

Brown University

Alpert Medical School

Geriatrician

Brown University Women and Infants

Division of Geriatrics Rhode Island Hospital Providence, Rhode Island Melissa Nothnagle, MD

Hospital Providence, Rhode Island Margaret Tryforos, MD

Clinical Assistant Professor

Assistant Professor of Family Medicine

Department of Family Medicine

Alpert Medical School

Alpert Medical School

Brown University

Brown University

Providence, Rhode Island

Providence, Rhode Island

Carolyn J. O'Connor, MD

Marc S. Weinberg, MD, FACP

Assistant Clinical Professor

Clinical Professor of Medicine

Yale University School of Medicine

Boston University School of Medicine

Department of Medicine

Clinical Associate Professor of Medicine

St. Mary's Hospital

Alpert Medical School

Waterbury, Connecticut

Chief of Nephrology

Steven M. Opal, MD

Professor of Medicine

Roger Williams Medical Center Providence, Rhode Island

Infectious Disease Division

Wen-Chih Wu, MD

Alpert Medical School

Associate Professor of Medicine

Brown University

Alpert Medical School

Providence, Rhode Island Paul A. Pirraglia, MD, MPH

Assistant Professor of Medicine Alpert Medical School

Brown University Cardiologist Providence VA Medical Center Providence, Rhode Island

Brown University Rhode Island Hospital Providence, Rhode Island Harlan G. Rich, MD

Director of Endoscopy Rhode Island Hospital Associate Professor of Medicine Alpert Medical School Brown University Providence, Rhode Island

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Th i s m a n u a l i s a c o n c i s e refe r e n c e for t h e b u sy c l i n i c i a n i n n e e d of i m m e d i ate m e d i c a l i n fo rmatio n . Its p u rpose is to p rovi d e a fast a n d effi c i e n t way to i d e ntify i m p o rtant c l i n i c a l , l a b o ratory, a n d d iagnostic i m a g i n g i n formati o n . T o l i m it its s i z e t o a pocket refe re n c e , l e s s e m p h a s i s h a s b e e n p l a c e d o n patho p h y s i o l ogy a n d e p i d e m i ol ogy, with m o re e m p ha s i s o n p racti c a l c l i n i c a l i n­ format i o n . C l i n ic a l a l gorith m s a n d t a b l e s have b e e n u s e d extensively t h ro u g h o u t t h e m a n u a l to s i m p l ify d iffi c u lt t o p i c s a n d to e n h a n c e rec o l l ecti o n of p r i n c i p a l p o i n t s . I t i s h o p e d t h at i t s c o n c i s e sty l e w i l l h e l p t h e read e r , p a rti c u l a rl y d u r i n g a n a ctive c l i n i c a l s e rvic e , w h e n t i m e to r e a d i s extre m e l y l i m ited . T h e c o m b i nati o n of p ractic a l c l i n ic a l i nformatio n with d rug therapeutics, p ro­ ced u re s , d i ag n o st i c i magi ng, a n d l a b o ratory m e d i c i n e m a ke s t h i s m a n u a l u n i q u e a n d u sefu l , n ot o n l y to m e d i c a l res i d ents a n d stu d ents b u t a l s o to p ractic i ng p h ys i c i a n s a n d a l l ie d h e a lt h p rofe s s i o n a l s . I w i s h to t h a n k t h e m a n y t h o u s a n d s of physi c i a n s w h o h ave m a d e t h e p r i o r e d i t i o n s a bestse l l e r i n m e d i c a l p u b l i sh­ ing and hope that futu re u s e rs w i l l fi n d this e d i t i o n the m o st u sefu l m e d i c a l h a n d b o o k that t h e y w i l l eve r p u rc h a s e d u ri ng t h e i r tra i n i ng .

Fred F . Ferri, MD, FACP

Pearls of Wisdom in Medicine 1 . C o m m o n t h i ngs o c c u r c o m m o n l y . 2 . W h e n y o u h e a r h oofbeats, th i n k of h o rses, n ot zebras. 3. Place y o u r bets o n u n c o m m o n m a n ifestat i o n s of common c o n d it i o n s , rathe r t h a n c o m m o n m a n i festat i o n s of u n c o m m o n c o n d i t i o n s . 4 . I f what y o u a re d o i n g i s worki n g , kee p o n d o i n g it. 5 . I f what y o u a re doing i s n ot worki ng, stop d o i ng it. 6 . I f y o u don't know w h at to d o , d o n 't d o a n yt h i ng . 7. Above a l l , n ever l et a s u rgeon g e t y o u r pat i e n t . From Matz R : Principles o f medicine. NV State J Med 77:99-101, 1977.

vii

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I also extend a special thanks to my sons, Dr. Vito F. Ferri and Dr. Ch ristopher A. Ferri for their help in the preparation and review of the man uscript and to the a uthors and contributors of the following texts who have served as a val uable resource in the development of the n i nth edition of this manual: Goldman L, Schafer AI (eds) : Goldman 's Cecil Medicine, 24th ed. Philadelphia, Saunders, 20 1 2 . Vincent JL, Abraham E, Moore FA, et al (eds) : Textbook of Critical Care, 6th ed. Phi ladelphia, Saunders, 20 1 1 . Medical Knowledge Self-Assessment Program (M KSAP) 16. Phi ladel phia, American College of Physicians, 20 1 2 . Gilbert D N , Moelleri ng RC , El iopoulos G M , et a l : The Sanford Guide to Anti m icrobial Therapy 20 1 3 , 43rd ed. Anti microbial Therapy, I nc, 20 1 2 . Users of our book are encouraged to use the above noted reference texts for ad­ d itional information on the topics discussed i n this manual .

Fred Ferri, MD

viii

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13. Chest pain (nonpleuritic)

1

Surviving the Wards

Chapter I: Surviving

the Wards

. . . . .

.

. . . . . . . . .

1. Admission orders

.1

1

. .1

2. Lab shorthand notation 3. Dictating the H&P

1

1

4. Progress (SOAP) note 5. Consult note

3

3

6. Discharge summary

3

3

8. Discharge against medical advice (AMA)

3

cutaneous

38

tomography 18. Cough

38

39

19. Cyanosis

39

20. Diplopia, binocular 21 . Dyspnea

39

39 40

23. Edema, generalized

C. Formulary...............34

extremities

40

34

hemidiaphragm

40

27. Emboli, arterial

40

28. Encephalopathy, metabolic

41

30. Fever and rash 31 . Flank pain

The Differential Diagnosis: Zebras or Horses?

35

Chapter 2: The Differential Diagnosis: Zebras or Horses? .

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

1. Abdominal distention 2. Abdominal pain 3. Adnexal mass

35

6. Amnesia

35

35

41

33. Genital discharge 34. Genital sores 36. Halitosis

37

42

42

37. Hearing loss, acute 38. Hemarthrosis 39. Hematuria

42

40. Hemiparesis/ 42

41 . Hemolysis and

44. Hirsutism 45. Hoarseness

43

43 43

43 44

10. Breast mass

37

46. Hydrocephalus

11. Breath odor

37

47. Hydronephrosis

ix

44 44

http://medical.dentalebooks.com 48. Hyperpigmentation 38

12. Bullous diseases

42

42

43. Hepatomegaly 37

41

42

35. Gynecomastia

hemoglobinuria

37

41

41

41

42. Hemoptysis

8. Arthritis and rash 9. Back pain

36

36

37

7. Anisocoria

.

32. Flushing

Hemiplegia

36

4. Adrenal masses 5. Amenorrhea

40

25. Edema of lower

29. Fever and jaundice

.

40

24. Edema, leg, unilateral

26. Elevated

B. Evaluating the labs.........4 1. IV Drips

38

17. Coma, normal computed

22. Dysuria

7. Pronouncing death while on call

15. Clubbing

38

16. Color changes,

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

A. Charting

38

14. Chest pain (pleuritic)

44

X

Contents 49. Hypertrophic

93. Vision loss, acute,

osteoarthropathy 50. Hypogonadism

44

painless

44

51. Hypopigmentation

94. Vision loss, chronic, progressive

44

52. Hypotension, postural 53. Jaundice

44

54. Joint swelling

45

emergent

45

56. Leg cramps, nocturnal

63. Mydriasis

47

.

47

66. Nail clubbing

A. Diagnostic aids in cardiology ..... ........ 53

47

67. Neck mass

47

68. Nystagmus

47

.

70. Palpitations

48

71. Papilledema

48

formulas

47

2. The cardiac cycle

5. Echocardiogram

75. Pneumonia, recurrent

48

49

83. Ptosis 85. Red eye

50

86. Seizures

50

88. Splenomegaly

70

C. Heart failure (HF) ........7 4 D. Valvular heart disease .. ..77 .

50

50

90. Urinary retention, 50 51

92. Vision loss, acute, painful

1. Cardiac murmurs

77

2. Mitral stenosis (MS) 50

78

3. Mitral regurgitation (MR)

80

4. Mitral valve prolapse (MVP)

81

5. Aortic stenosis (AS) http://medical.dentalebooks.com

51

66

2. Coronary artery syndromes (ACS)

89. Taste and smell loss

91. Vertigo

66

1. Chronic stable angina

49

87. Spastic paraplegias

acute

64

B. Coronary artery disease....66

49

49 50

64

7. Central venous access

Ganz)

49

84. Purpura

60

catheterization (Swan­

49

82. Pruritus ani

60

8. Pulmonary artery (PA)

49

80. Proteinuria

(A-line)

(CVP line)

49

78. Postmenopausal 79. Proptosis

53

6. Radial artery cannulation

48

77. Popliteal swelling

53

4. Cardiac stress testing

48

74. Pelvic mass

53

3. ECG: interpretation

48

73. Paresthesias

.

1. Cardiovascular

69. Ophthalmoplegia

72. Paraplegia

53

Chapter 3: Cardiovascular Disease.. .................53

47

81. Pruritus

52

Diseases and Disorders

46

64. Myelopathy and

bleeding

51

46

62. Muscle weakness

76. Polyuria

51

99. Weight loss

46

46

myelitis

51

51

98. Weight gain 100. Wheezing

59. Livedo reticularis

65. Myotonia

51

45

60. Lymphadenopathy 61. Miosis

45

45

58. Leukocoria

95. Visual field defects 97. Weakness, acute,

55. Jugular venous

57. Leg ulcers

51

96. Vocal cord paralysis

45

distention

51

81

xi

Contents 6. Aortic regurgitation (AR), aortic insufficiency (AI)

83

7. Infective endocarditis 8. Prosthetic valves

84

86

87

88

3. Cardiac tamponade

89

4. Constrictive 89

90

90

91

99

4. Atrial fibrillation and atrial flutter

100

a. Atrial fibrillation

100

105 1 06

a. Paroxysmal atrial

tachycardia

G. Cardiomyopathies.. .. . ..92 .

.

1. Dilated (congestive) cardiomyopathy cardiomyopathy

tachycardia (MAT) (SSS, tachy-brady

syndrome, brady-tachy

4. Arrhythmogenic right

syndrome)

ventricular dysplasia

arrhythmias

5. Takotsubo

.

.

.

.

94

.. 94 .

.

I. Diseases of the aorta ......95 1. Thoracic aortic

109

syndrome

11 0

c. Brugada syndrome (VT)

2. Acute aortic

11 0

110

e. Torsades de

syndromes (aortic

pointes

dissection, intramural hematoma, penetrating 3. Abdominal aortic

(LOTS)

b. Short OT

d. Ventricular tachycardia

95

atherosclerotic ulcer)

109

a. Long OT syndrome

cardiomyopathy (stress cardiomyopathy, SC)

108

6. Ventricular

94

.

1 08

d. Sick sinus syndrome

93

.

107

multifocal atrial

92

cardiomyopathy

.

106

c. Atrial tachycardia,

3. Hypertrophic

.

[PSVT])

b. Wolff-Parkinson-White syndrome (WPW)

92

2. Restrictive

aneurysm

99

supraventricular

5. Tetralogy of Fallot

.

2. Pacemakers

paroxysmal

91

H. Myocarditis .

98

tachycardias (PAT,

4. Patent ductus arterious

(ARVD)

block

tachycardias (SVT)

3. Ventricular septal defect

(HCM)

97

5. Supraventricular

90

(PDA)

block

b. Atrial flutter

2. Atrial septal defect

(VSD)

97

b. Second-degree heart

with tachycardia

1. Patent foramen ovale

(ASD)

a. First-degree heart

3. Approach to the patient

F. Adult congenital heart disease. .. .... ...........90 (PFO)

97

c. Third-degree heart

2. Pericardia! effusion

pericarditis

.

1. AV conduction defects block

E. Pericardia! disease........87 1. Pericarditis

J. Arrhythmias ... .........97

96

1 11

K. Peripheral arterial disease (PAD) . .. .. ....112 .

.

L. Cardiac risk assessment for noncardiac surgery....113 http://medical.dentalebooks.com

aneurysm

97

:xii

Contents

M. Hypotension .. .. .. . ... ..113 N. Acute cardiogenic shock..................115 0. Dyslipidemia............115

P. Metabolic syndrome......117 Q. Syncope................117 R. Hypertension............118 1. Hypertensive crises

1 19

2. Renal artery stenosis (RAS)

hypothyroidism

Chapter 4: Dermatology....122 A. Herpes zoster (shingles). .. 122 B. Pressure ulcers..........122 C. Psoriasis . .... ... ..... ..123

7. Thyroiditis

141

nodule

141

9. Thyroid carcinoma

1. Calcium formulas

1 26 130

B. Hypoglycemia ...........130 C. Anterior pituitary disorders...............131 131

2. Anterior pituitary hyperfunction secondary to pituitary neoplasms

134

D. Fluid hemostasis disorders...............135 1. Diabetes insipidus

2. Primary adrenocortical insufficiency (Addison's disease)

149

mineralocorticoid 1 50

a. Hypoaldosteronism

150

(Conn's syndrome)

150

H. Pheochromocytoma. .. . ..151 I. Carcinoid syndrome.... ..152 J. Multiple endocrine neoplasia...............152

Chapter 6: Gastroenterology..........154 A. Acute gastrointestinal bleeding .... ...... ... ..154 B. Disorders of the esophagus. .. ...... .. ..156 .

135

1. Dysphagia

2. Syndrome of inappropriate antidiuretic hormone (SIADH, SIAD) 135

Interpretation of thyroid

function studies 2. Hyperthyroidism

156

a. Oropharyngeal dysphagia

1 37 138

1 56

2. Esophageal motility disorders 3. GERD

156

1 57

4. Barrett's esophagus

1 39 http://medical.dentalebooks.com

3. Thyroid storm

1 56

b. Esophageal dysphagia

E. Thyroid disorders........137 1.

1 47

b. Hyperaldosteronism

2. Hyperosmolar non-ketotic

secretion

145

1. Cushing's syndrome

secretion

(DI)

143

1 43

G. Adrenal gland disorders.... .. .... .. . ..147

A. Diabetes mellitus (DM). . .124

1. Hypopituitarism

1 42

F. Calcium homeostasis disorders.... .. .... ... ..143

Chapter 5: Endocrinology ..124 1. Diabetic

1 41

8. Evaluation of thyroid

3. Disorders of

coma, honk

141

6. Myxedema coma

3. Hypocalcemia

121

ketoacidosis

139

5. Subclinical

2. Hypercalcemia

1 19

3. Eclampsia

4. Hypothyroidism

5. Esophageal tumors

157 158

xiii

Contents

C. Disorders of stomach and duodenum..............158 158

1. Peptic ulcer disease

2. Viral hepatitis

1 74

a. Hepatitis A

1 74

b. Hepatitis B

1 77 1 78

2. Gastroparesis

1 59

c. Hepatitis C

3. Gastric cancer

1 59

d. Hepatitis D

180

e. Hepatitis E

180

D. Disorders of the pancreas ...............160 1. Acute pancreatitis

1 60

2. Chronic pancreatitis

162

3. Pancreatic adenocarcinoma

163

4. Neuroendocrine

a. Gastrinoma

163

1 64

1 66

4. Celiac disease

1 67

167 168 170

7. Irritable bowel 170 1 71

10. Small bowel

188 1 88

i. Fulminant hepatic failure (FHF)

189 189

1 90

a. Budd-Chiari

172

syndrome thrombosis

b. Mesenteric

7. Hepatic cysts

173

13. Colorectal neoplasia

173

a. Colorectal 1 73

F. Disorders of the liver.....17 4 1. Approach to the pt

with abnormal liver

1 90

b. Portal vein

1 72

174

187

peritonitis

liver

a. Mesenteric

enzymes

(HRS)

g. Spontaneous bacterial

6. Vascular disorders of the

1 72

12. Ischemic bowel

Carcinoma

186

f. Hepatorenal syndrome

j. Liver abscess

172

thrombosis

1 86

carcinoma (HCC)

1 70

ischemia

184

186

h. Hepatocellular

9. Diverticular disease

disease

Paracentesis c. Varices

(HE)

b. Ulcerative colitis

11. Adynamic ileus

182

b. Ascites/

encephalopathy

a. Crohn's disease

obstruction

182

hypertension

167

6. Microscopic colitis

181

e. Hepatic

5. Inflammatory bowel

syndrome

181

d. Portal

166

8. Appendicitis

cirrhosis (PBC)

a. Cirrhosis

3. Malabsorption

disease

181

a. Primary biliary

disease

163

2. Constipation

disease

5. Complications of liver

E. Disorders of small and large bowel ... ......... .164 1. Diarrhea

180

cholangitis (PSC)

1 63

b. lnsulinoma

hepatitis

4. Cholestatic liver

b. Primary sclerosing

pancreatic neoplasms

3. Autoimmune

1 90 191

8. Hepatic adenoma (HA)

191

G. Metabolic liver disease ...191 1. Alcoholic hepatitis

191

2. Nonalcoholic fatty liver disease (NAFLD)

1 92

3. Hereditary

hemochromatosis http://medical.dentalebooks.com

192

:xiv

Contents 4.

a

1-Antitrypsin

deficiency

2. Pure red cell aplasia

1 93

(PRCA)

5. Wilson's disease

1 93

H. Disorders of gallbladder...193 1. Cholelithiasis

1 93

2. Acute cholecystitis

1 94

Chapter 7: Hematology! Oncology .................195 A. Approach to the patient with anemia ............195 1. Anemia secondary to

195

c. Folate deficiency

196

(anemia of chronic disease [ACD])

197

197

206 206

(AML)

207

leukemia (ALL)

207

E. Multiple myeloma and related disorders . . . . . . . . . . . . . 207 207

2. Monoclonal gammopathy

197

of undetermined

a. Autoimmune hemolytic anemia (AIHA)

197

hemolytic anemia

198

c. Paroxysmal nocturnal hemoglobinuria

209

3. Waldenstrom's 4. AL amyloidosis

209

209

F. Lymphoid malignancies .. .209 1. Non-Hodgkin's

198

d. Hemolytic transfusion 1 99

3. Congenital hemolytic 1 99

lymphoma

209

2. Chronic lymphocytic leukemia (CLL)

21 0

3. Hairy cell leukemia

212

4. Hodgkin's lymphoma

a. Sickle cell syndrome

significance (MGUS) macroglobulinemia

b. Microangiopathic

anemias

205

6. Acute lymphoblastic

(MM)

2. Acquired hemolytic

reaction

thrombocythemia

1. Multiple myeloma

e. Sideroblastic

(PNH)

204

2. Essential

myelofibrosis

d. Inflammatory anemia

anemia

1. Polycythemia vera

5. Acute myeloid leukemia

b. Cobalamin (vitamin

anemia

D. Myeloproliferative disorders . . ...... . ......204

4. Primary

1 95

B 12l deficiency

202

202

C. Myelodysplastic syndromes. ...... . ......204

leukemia

195

a. Iron deficiency anemia

4. Neutropenia

3. Chronic myeloid

maturation defects or underproduction

201

3. Thrombocytopenia

199

b. Thalassemia

200

c. Glucose-6 phosphate

212

G. Bleeding disorders.......213 1. Evaluation of suspected bleeding disorder

21 3

dehydrogenase (G6PD)

2. Hemophilia

deficiency

3. Von Willebrand's disease

201

d. Hereditary spherocytosis

(vWD) 201

B. Bone marrow failure syndromes ...... . ...... .201 1. Aplastic anemia

21 3

213

4. Coagulopathy of liver disease

21 4

5. Disseminated intravascular coagulation (DIC)

21 5

201 http://medical.dentalebooks.com 6. Vitamin K deficiency

21 5

XV

Contents

H. Platelet disorders .. ......216 1. Immune (idiopathic)

thrombocytopenic purpura (ITP)

216

E. Skin/Soft tissue/Bone/Joint infections ... .. . .. . ... ..237 1. Cellulitis

Staphylococcus aureus 239

2. Heparin-induced thrombocytopenia (HIT)

3. Toxic shock syndrome

216

(TSS)

3. Thrombotic thrombocytopenic purpura (TTP)

infections

syndrome (HUS)

218

1. Hypercoagulable 21 9

2. Antiphospholipid

gangrene") 7. Bites

220

242

10. Septic bursitis

242

a. Scabies

scabei)

224

2. Superior vena cava 224

3. Brain metastases

224

Chapter 8: Infectious Diseases ...... .. . ... .... ..226 A. HIV/AIDS . ..............226 B. Hospital-acquired infections ........ . ..... 232 C. Pneumonia . ...... ... ...233 D. Abscess ..... ..... ......234 1. Breast abscess/

243

2. Lung abscess

234

3. Liver abscess

235

G. Sexually transmitted diseases ..... .. . ... ... ..244 trachomatis

1. Chlamydia infection 2.

244

Neisseria gonorrhoeae infection

244

3. Pelvic inflammatory disease (PID)

246

4. Genital warts

24 7

5. Vaginitis

24 7

6. Genital ulcers a. Syphilis

24 7

24 7

b. Herpes simplex virus

ducreyi)

248

(Haemophilus

249

d. Lymphogranuloma venereum (LGV)

236

6. Peritonsillar abscess 7. Retropharyngeal

244

F. Fever of unknown origin (F UO ) ....... ...... ......244

c. Chancroid

235

5. Perirectal abscess

237

243

c. Lice (pediculosis)

(HSV) infection

234

4. Pelvic abscess

243

(Sarcoptes

b. Bed bugs

1. Tumor lysis

abscess

241

11. Skin infestations

J. Oncologic urgencies and emergencies ...... ......224

Mastitis

241

9. Septic arthritis

221

syndrome

241

8. Osteomyelitis

3. Venous thromboembolism

syndrome

240

6. Muscle ("gas

218

I. Thrombotic disorders . .. . 219

(DVT)

240

5. Necrotizing fasciitis

5. HELLP syndrome

syndrome

239

4. Diabetic foot

218

4. Hemolytic-uremic

state

237

2. Methicillin-resistant

236

2 50

7. Male genital tract infections

2 50

a. Balanitis

2 50

b. Epididymo-orchitis

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2 50

:xvi

Contents

H. Infectious GI syndromes . . . . . . . . . . . 250 .

1.

.

Clostridium difficile

infection (CDI) 2. 3.

2 51

2 52

Shigella infection

a. Amebiasis b. c.

2 54 255

infection

2 55

2 56

2 56

b. Secondary (bowel

diverticula)

.

2. Bacterial meningitis 3. Viral meningitis

2 56

2 58

2 60

9. Tinea

271

271

272

M. Viral infections . . . . . . . . . 272 1. Influenza

2 72

2. Herpes simplex (HSV) .

.

2 73

. . . . . . . . 274

Chapter 9: Nephrology . . . . . 277

2 60

encephalitis

1. Approach to acid-base disorders

(RTA)

b. West Nile virus (WNV) encephalitis

D. Acid-base disorders . . . . . . 277 2 77 2 78

3. Renal tubular acidosis

2 60 2 61

5. Brain abscess

C. Replacement fluids . . . . . . 277

2. Metabolic acidosis

a. Herpes simplex

2 80 2 81

4. Respiratory acidosis

2 82

5. Metabolic alkalosis 6. Respiratory alkalosis

2 61

6. Spinal epidural abscess 2 62

285

E. Disorders of sodium homeostasis . . . . . . . . . . . 286 .

7. Subdural empyema

263

J. Urinary tract infections . . . 263 2 63

2. Pyelonephritis

2 63

3. Perinephric abscess

2 64

.

1. Lyme disease

265

2. Ehrlichiosis and anaplasmosis

1. Hyponatremia

2. Hypernatremia

265

1. Hypokalemia

288

290

1. Hypomagnesemia

2. Hypermagnesemia

266 2 66

287

G. Disorders of magnesium metabolism . . . . . . . . . . . . . 292

4. Rocky Mountain spotted fever (RMSF)

286

F. Disorders of potassium homeostasis . . . . . . . . . . . . 288 2. Hyperkalemia

2 64

K. Tick-borne diseases . . . . . 265

3 . Babesiosis

2 70

7. Coccidioidomycosis

.

.

1. Lumbar puncture (LP)

4. Prostatitis

2 70

B. Water balance . . . . . . . . . . 277

2 56

I. Central nervous system infections . . . . . . . . . . . . 256

1. Cystitis

5. Mucormycosis

.

ruptured appendix/

(SEA)

2 69

A. Renal fluid and electrolyte formulas . . . . . . . . . . . . . . 277

perforation,

4. Encephalitis

2 68

2 69

4. Blastomycosis

N. Tuberculosis . .

2 56

a. Primary (SBP)

2 66

.

255

Giardia infection Cryptosporidium

7. Peritonitis

2. Histoplasmosis

8. Sporotrichosis

5. Vancomycin-resistant 6. Parasitic infections

1. Systemic candidiasis

6. Cryptococcosis

2 52

enterococci (VRE)

L. Fungal infections . . . . . . . . 266 3. Aspergillosis

2 50

Salmonella infection Campylobacter infection

4.

.

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292

293

xvii

Contents

H. Disorders of phosphate metabolism. . . . . . . . . . . . .293 1. Hypophosphatemia

293

2. Hyperphosphatemia

294

J. Acute kidney injury (AKI)..................294 K. Chronic kidney disease (CDK) .................294 L. Glomerular disease . . . . . . 298 1. Nephrotic syndrome

298

2. Nephritic syndrome

300

M. Tubulointerstitial disorders . . . . . . . .. . . . 302 .

.

.

1. Acute tubular necrosis

0. Urolithiasis . . . . . . .. . . 303 .

.

Chapter 10: Neurology.. . . . . 306 A. Diagnostic aids . . . . . . . . . 306 .

1. Spinal dermatomes

306

2. Key areas determining sensory level

306

3. Key muscles determining 306

5. Grading of deep tendon 306

(SAH)

31 5

4. Sinus venous thrombosis . . . . . . .. . . . . . 317 5. Stroke prevention:

asymptomatic carotid stenosis................317

D. Headaches .. . . . . .. . . . . . 318 1. Migraine (aura, 318

(bilateral, vice-like)

319

3. Cluster headache (unilateral, lacrimation, periorbital)

319

4. Idiopathic intracranial hypertension (IIH; pseudotumor cerebri)

320

E. Movement disorders . . . . . 321 1. Parkinson's disease 321 322

3. Essential tremor 4. Dystonia

(TD)

B. Epilepsy. . . . . . . . . . . . . . . . 306 1. Partial (focal

306

322

322 323

323

7. Myoclonus

324

8. Tourette's syndrome 9. Wilson's disease

2. Idiopathic general epilepsy

hemorrhage

6. Tardive dyskinesia

306

epilepsy)

31 4

b. Subarachnoid

5. Chorea

6. Testing of cranial nerves

hemorrhage

2. Ataxia

306

reflexes

a. Intracranial

(PD)

4. Grading of muscle strength

31 4

2. Tension-type headache

N. Kidney cystic disorders ...303

motor level

stroke

trigger)

302

.

3. Acute hemorrhagic

324

10. Restless legs syndrome

309

(RLS)

3. Status epilepticus

324

31 0

32 5

F. Dementia ... . . . . .. . . . . . 325 .

C. Stroke . . . . . . . . . . . . . . . . 310 .

1. Transient ischemic attack (TIA)

310

2. Ischemic stroke

312

G. Multiple sclerosis (MS) . . . 327 H. Disorders of the spinal cord .. . . . . .. . . . . . 329 1. Compressive myopathies

http://medical.dentalebooks.com

329

:xviii

Contents 2. Infectious myopathies

330

myopathies

330

or widening on chest x-ray

330

5. Idiopathic transverse myelitis

331

I. Peripheral neuropathies ...........331 1. General approach

331

2. Mononeuropathies

331

a. Carpal tunnel syndrome

332

3. Polyneuropathies

333

333

b. Charcot-Marie-Tooth disease (CMT)

333

c. Guillain-Barre syndrome (GBS)

334

demyelinating

K. Neuromuscular junction disorders ..... ....... .336 .

1. Myasthenia gravis 336

2. Lambert-Eaton myasthenic 336

337

2. Subdural hematoma 3. Concussion

337

338

A. Chest x-ray .............340 1. Evaluating the chest 340

.

.

H. Pulmonary vascular disease ..... ..........358 1. Pulmonary embolism 358 362

I. Diffuse parenchymal lung disease ................364 1. Interstitial lung disease (ILD)

364

J. Granulomatous lung disease ................365 1. Sarcoidosis

365

polyangiitis (Wegener's granulomatosis)

366

K. Pleural disease ..........367 Thoracentesis

367

L. Lung cancer .. ..... . .368 .

.

.

M. Respiratory failure classification ...........371 respiratory failure

340

3. Cardiac enlargement

.

1. Hypoxemic ("type I")

2. Calcifications on chest x-ray

.

1. Pleural effusion/

Chapter 11: Pulmonary and Critical Care ..........340 x-ray

G. Chronic obstructive pulmonary disease (COPD) .... ..... ... 356

2. Granulomatosis with

L. Head injury .............337 1. Epidural hematoma

F. Asthma ................352

hypertension

.

syndrome

D. Mechanical ventilation ...345

2. Pulmonary

334

J. Amyotrophic lateral sclerosis (ALS) ... ......335

(MG)

C. Pulmonary formulas .....344

(PE)

polyneuropathy

.

.

.

d. Chronic inflammatory

(CIDP)

B. Use and interpretation of pulmonary function tests ..... .............343

.

a. Diabetic neuropathy

342

E. Acute respiratory distress syndrome (ARDS) ...... 352

331

b. Bell's palsy

342

5. Mediastinal masses

4. Endocrine-related myopathies

4. Cavitary lesion on chest x-ray

3. Inflammatory

340

371

2. Hypercapnic ("type II") respiratory failure

http://medical.dentalebooks.com

371

xix

Contents

Chapter 12: Rheumatology .372 A. Arthrocentesis

.

.

.

.

.

.

.

.

.

.

372

B. Arthritis, monarticular and oligoarticular .......373 C. Arthritis, polyarticular ...373 D. Vasculitic syndromes.....373 E. Systemic lupus erythematosus (SLE)..................373 F. Rheumatoid arthritis (RA)...................380 G. Spondyloarthropathies

.

.

.

381

H. Systemic sclerosis .......382 I. Enteropathic arthritis....384 J. Crystal-induced arthritides..............384 1. Gout

384

E. Malignant hyperthermia

.

Chapter 13: Interdisciplinary

Medicine .................387

A. Rhabdomyolysis .........387 B. Shock..................388 . C . Hypothermia............388 D. Heat stroke.............394

.

.

.

.

.

.

.

.

.

395

F. Neuroleptic malignant syndrome (NMS) ........396 G. Anaphylaxis ............396 H. Alcohol withdrawal ......397 I. Acute poisoning .........398 1. Acetaminophen poisoning

398

2. Amphetamine overdose

400

3. Barbiturate overdose

400

4. Cocaine overdose

401

5. Ethanol poisoning

402

6. Ethylene glycol, isopropyl alcohol, and methanol poisoning

402

7. Carbon monoxide poisoning

K. Idiopathic inflammatory myopathies .............386

.

Append'IX

.

.

.

•

.

.

403 •

.

.

.

.

•

.

1. Cardiac arrest algorithm

.

.

•

.405

405

2. Immediate post­ cardiac arrest care algorithm

406

3. Bradycardia with a pulse algorithm

407

4. Tachycardia with a pulse algorithm

http://medical.dentalebooks.com

408

>


90% of pts w/chronic ITP) . Pts w/nonimmune throm bocytopenias

may have false-(+) results.

PLATELET COUNT

Nl range: 1 30-400 x 1 0 3/mm 3 . t: iron deficiency, after hemorrhage, neoplasms (GI tract) , C M L, PV, myelofibrosis

w/myeloid metaplasia, infections, after splenectomy, post partum , hemoph i l i a , pancreatitis, cirrhosis. !: see "Th rombocytopenia" in Chapter 7.

PLATELET FUNCTION ANALYSIS (PFA- 1 00 ASSAY) Nl: Test is a two-component assay i n which blood is aspirated th rough two capillary

tubes, one of which is coated w/collagen and ADP (COUADP) and the other w/ col lagen and epinephrine (COUE P I ) . The test measures the abil ity of Pits to occlude a n aperture i n a biologically active membrane treated with COUADP and COUEPI . During the test, the Pits adhere to the surface of the tube and cause blood flow to cease. The closing time refers to the cessation of blood flow and is reported i n conjunction w/the Hct and Pit count. Hct count m ust be >25% and Pit count >50 Kf�tl for the test to be performed . • COUADP : 7 0- 1 20 seconds • COUEPI : 7 5- 1 20 seconds f: acquired Pit dysfunction, vWD , anemia, thrombocytopen ia, use of ASA and N SAIDs.

POTASSIUM (K+) (SERUM) Nl range: 3 . 5-5 m Eq/L.

t or !: see " Hypokalemia" and " Hyperkalemia" in Chapter 9 .

PROGESTERONE (SERUM) Nl:

• Female: 1 5-70 ng/d l (follicular phase) ; 200-2500 ng/d l (luteal phase) • Male: 1 5-70 ng/d l t: congenital adrenal hyperplasia, clomiphene, corticosterone, 1 1 -deoxycortisol , dihyd roprogesterone, molar pregnancy, l i poid ovarian tumor. !: primary or secondary hypogonadism, oral contraceptives, ampici l l i n , th reatened abortion.

PROLACTI N Nl range: 200 h ighly suggestive) , d rugs (phenoth iazines, ci metidine,

tricyc l i c antidepressants, metoclopramide, estrogens, a nti hypertensives [ m ethyldopa , verapa m i l ] , hal operidol) , post partum , stress, hypoglycemia, hypothyroidism.

PROSTATE-SPECIFIC ANTIGEN (PSA) Nl range: 0-4 ng/m l. There is no PSA level below which prostate cancer can be ruled

out and no level above which prostate cancer is certa i n . The individua l ' s PSA level is only part of the equation. Other risk factors need to be considered , such as age, race , FHx, fi ndi ngs on digital rectal exami nation, percentage free PSA ratio, and PSA velocity (rate of change from prior PSA measurement) . t: BPH, carci noma of prostate , after rectal examination, prostate trauma, androgens, prostatitis, urethral instrumentation. Note: Measurement of free PSA is useful to assess the probabil ity of prostate cancer i n pts w/nl fi ndi ngs on digital rectal exami nation and total PSA level between 4 and 1 0 ng/m l. I n these pts, the global risk of prostate cancer is 25% to 40%. However, if the free PSA is >25%, the risk of prostate cancer ! to So/a; whereas if the free PSA is < 1 Oo/o, the risk of cancer l to 56%. Free PSA is also useful to eval uate the aggressiveness of prostate cancer. A low free PSA percentage generally indicates a h igh-grade cancer, 25 whereas a h igh free PSA percentage is generally associated w/a slower growing tumor. !: fi nasteride, dutasteride, bed rest, antiandrogens. http://medical.dentalebooks.com

PROSTATIC ACI D PHOSPHATASE Nl: 0-0 .8 U/L. t: prostate cancer (especially in metastatic prostate cancer) , B P H , prostatitis, after

prostate surgery or manipu lation, hemolysis, androgens, clofibrate. !: ketoconazole Rx.

PROTEI N (SERUM) Nl range: 6-8 g/d l. t: dehydratio n , sarcoidosis, collagen-vascular diseases , M M , Waldenstrom's

macroglobulinemia. !: malnutrition, cirrhosis, nephrosis, low-protei n diet, overhydration, malabsorption, pregnancy, severe burns, neoplasms, chronic diseases.

PROTEI N C ASSAY Nl: 7 0%- 1 40%. t: oral contraceptives, stanozolol.

!: congenital protei n C deficiency, warfarin Rx, vitamin K deficiency, renal insufficiency, consumptive coagulopath ies.

PROTEI N ELECTROPHORESI S (SERUM) Nl range:

t:

!:

• Alb: 60%-7 5%; 3 . 6-5.2 g/d l • a 1 : 1 . 7%-5%; 0 . 1 -0 . 4 g/dl • a2 : 6 . 7 %- 1 2 . 5%; 0 . 4- 1 . 0 g/d l • �: 8 . 3%- 1 6 . 3%; 0 . 5- 1 .2 g/d l • Gamma: 1 0. 7%-20%; 0 . 6- 1 . 6 g/d l

• Alb: dehyd ration • a 1 : neoplastic diseases, i nflam mation • a2 : neoplasms, i nflam matio n , i nfection , nephrotic syndrome • � : hypothyroidism, bil iary ci rrhosis, DM • Gamma: see " I m m unoglob u l i n s , " earl ier • Al b: maln utrition, chronic l iver disease , malabsorption, nephrotic syndrome, burns, SLE • a 1 : emphysema (a 1 -antitrypsin deficiency) , nephrosis • a2 : hemolytic anemias (! haptoglobi n), severe hepatocellular damage • �: hypocholesterolemia, nephrosis • Gamma: see " I m m unoglobulins, " earl ier

PROTEIN S ASSAY Nl: 65%- 1 40%. t: presence of l upus anticoagu lant.

!: hereditary deficiency, acute thrombotic events, DIC, surgery, oral contraceptives, pregnancy, hormone replacement Rx, L-asparaginase Rx.

PROTHROMBIN TIME (PT)

Nl range: 1 1 - 1 3 . 2 seconds.

Note: The PT is reported as absolute clotting time i n seconds and also as a derivative n umber called the I N R. Thi s ratio is derived from the actual PT of the pt divided by the mean PT of a group of healthy subjects. I N R should always be used in i nterpreti ng PT. t: l iver disease , oral anticoagu lants (warfarin), hepari n , factor deficiency ( 1 , I I , V , VI I , X) , D I C , vitamin K deficiency, afibrinogenemia, dysfi brinogenemia, drugs (salicylate , chloral hyd rate , diphenyl hydanto i n , estrogens, antacids, phenylbutazone, quinidine, abx, allopurinol, anabolic steroids) . !: vita m i n K supplementation , thromboph lebitis, drugs (gl uteth imide, estrogens, griseofulvi n , di phen hydramine).

PROTOPORPHYRIN (FREE ERYTHROCYTE) Nl range: 1 6-36 f!g/dl of RBCs. t: iron deficiency, lead poisoni ng, sideroblastic anemias, anemia of chronic disease,

hemolytic anemias, erythropoietic protoporphyria.

PSA; SEE PROSTATE-SPECIFIC ANTICEN (PSA)

2 6 PT; SEE PROTHROMBIN TI M E (PT)

PTT; SEE PARTIAL THROMBOPLASTIN TI ME (PTT) http://medical.dentalebooks.com

RDW; SEE RED BLOOD CELL DISTRIBUTION WIDTH (RDW) RED BLOOD CELL COUNT

Nl range: 4. 3-5 .9 x 1 06/mm 3 (male); 3 . 5-5.0 x 1 06/m m 3 (female) . 1': hemoconcentration and dehydration, stress, PV, smokers, h igh altitude, CV disease , renal cell carcinoma and other erythropoietin-producing neoplasms. !: anemias, hemolysis, chronic renal fail ure, hemorrhage , fai l ure of marrow production.

RED BLOOD CELL DISTRIBUTION WIDTH (RDW) RDW measures variabil ity of red cell size (anisocytosis)

Nl range: 1 1 . 5- 1 4 . 5 .

N l RDW and: • l MCV: aplastic anemia, preleukem i a . • N l MCV: n l , a n e m i a o f chronic disease, acute blood loss or hemolysis, CLL, C M L, nonanemic enzymopathy or hemoglobinopathy. • l MCV: anemia of chronic disease, heterozygous thalassemia. l RDW and: • l MCV: vitamin B 1 2 deficiency, folate deficiency, immune hemolytic anemia, cold aggl utinins, CLL w/high count, l iver disease. • N l MCV: early i ron deficiency, early vita m i n B 1 2 deficiency, early folate deficiency, anemic globinopathy. • l MCV: i ron deficiency, RBC fragmentation, HbH disease, thalassemia intermedia.

RED BLOOD CELL FOLATE ; SEE FOLATE RED BLOOD CELL MASS (VOLUME) Nl range:

• Male: 2 0-36 m Ukg of BW ( 1 . 1 5- 1 . 2 1 Um 2 BSA) • Female: 1 9-3 1 m Ukg of BW (0.95- 1 . 00 Um 2 BSA) 1': P vera, hypoxia (smokers, high altitude, CV disease) , hemoglobinopath ies w!l0 2 affi n ity, erythropoietin-producing tumors (renal cell carcinoma) . !: hemorrhage, chronic disease, fai l u re of marrow production, anemias, hemolysis.

REN I N (SERUM)

t: renal HTN , reduced plasma volume, secondary aldosteron ism, drugs (th iazides, estroge n , m i noxidil). chronic renal fai l u re, Bartter's syndrome, pregnancy (nl) , pheochromocytoma. !: primary aldosteronism, adrenocortical HTN , l in plasma volume, drugs (propranolol , reserpine, clonidi ne) .

RETICULOCYTE COUNT Nl range: 0 . 5%- 1 .5%. 1': hemolytic anemia (sickle cell crisis, thalassemia major, autoimmune hemolysis) ,

hemorrhage , after anemia Rx (folic acid, ferrous su lfate, vita m i n B 1 2 ) , chron ic renal fai l u re . !: aplastic anemia, marrow suppression (sepsis, chemotherapeutic agents, radiation) , hepatic cirrhosis, blood transfusion, anemias of disordered maturation (iron deficiency anemia, megaloblastic anemia, sideroblastic anemia, anemia of chronic disease) .

RHEUMATOI D FACTOR (RF) Nl: (-)

Present in titer > 1 : 2 0 : RA, SLE, chronic inflammatory processes, old age , infections, l iver disease, MM, sarcoidosis, pulmonary fibrosis, Sjogre n ' s syndrome.

RNP; SEE EXTRACTABLE NUCLEAR ANTIGEN SEDIMENTATION RATE; SEE ERYTHROCYTE SEDIMENTATION RATE SEMEN ANALYSIS Nl:

• Vol ume: 2-6 m l • Sperm density: > 2 0 m i l l ion/m l • Total number of spermatozoa : >80 m i l l ion/ejaculate • Progressive motil ity score eval uated 2-4 hr after ejaculate: 3-4 • Live spermatozoa : :::: 5 0% of total • Nl spermatozoa: :::: 6 0% of total • I mmature forms: 99o/o of circulating T4 and unbound [free] thyroxine) . Val ues vary w/protei n binding; changes in the concentration of T4 secondary to changes i n TBG can be caused by the fol lowing: • l TBG ( lTJ pregnancy, estrogens, acute i nfectious hepatitis, oral contraceptives, fam i l i a l , fl uorouracil, clofi brate , heroin, methadone. • ! TBG (! T4 ) : androgens, glucocorticoids, nephrotic syndrome, cirrhosis, acromegaly, hypoproteinemia, fam i l i a l , phenyto i n , ASA and other N SAI Ds, h igh­ dose PCN , asparagi nase, chronic debil itating i l l ness. To elimi nate the suspected i nfl uence of protein binding on thyroxine val ues, two additional tests are available: T resin uptake and serum free thyroxine. 3 Serum free T4 di rectly measures unbound thyroxine. Free T4 can be measured by equilibrium dialysis (gold standard of free T4 assays) or by i m m u nometric techniq ues (infl uenced by serum levels of l i pids, proteins, and certai n drugs) . The FTI can also be easily calculated by m u ltiplyi ng \ times T RU and dividing 3 the result by 1 00; the FTI corrects for any abnl T4 val ues secondary to protei n binding: FTI T4 x T RU/ 1 00. N l val ues equal 1 . 1 to 4 . 3 . 3 =

TESTOSTERONE N l range: variable with age a n d sex.

28

• Serum/plasma: 1 70- 1 000 ng/d l (males) ; 1 5-70 ng/dl (females) • Urine: 50- 1 35 11g/day (males) ; 2- 1 2 11g/day (females) l: adrenogenital syndrome, polycystic ovary disease . !: Kl inefelter's syndrome, male hypogonadism. http://medical.dentalebooks.com

THIAMINE N l : 2 7 5-675 ng/g. t: PV, leukemia, Hodgki n ' s disease. !: alcoholism, dietary deficiency (beriberi ) , excessive consumption of tea (contains antith iamine factor) or raw fish (contains a m icrobial thiam i nase ) , chronic i l lness, prolonged i l l ness, barbiturates.

THROMBIN TIME (TT) Nl range: 1 1 . 3- 1 8 . 5 seconds. t: thrombolytic and heparin Rx, DIC, hypofi brinogenemia, dysfibrinogenemia.

THYROG LOBULIN Nl: 3-40 ng/m l. Thyroglobul i n is a tumor marker for mon itoring the status of pts w/

papillary or fol l icular thyroid cancer after resection. t : papi llary or follicular thyroid cancer, Hashi moto ' s thyroiditis, G raves ' disease, subacute thyroiditis.

THYROID MICROSOMAL ANTI BODIES Nl: undetectable. Low titers may be present i n 5% to 1 0% of n l individuals. t: Hashi moto 's disease, thyroid carcinoma, early hypothyroidism, pernicious anemia.

THYROI D-STIMULATI NG HORMONE (TSH) Nl: 2-6 U/m l. t: see " H ypothyroidism" and " Hyperthyroidism" in Chapter 5 .

THYROTROPIN (TSH) RECEPTOR ANTIBODIES Nl: < 1 30 % of basal activity. t : val ues between 1 . 3 and 2 . 0 are found i n 1 0% of pts w/thyroid disease other than Graves' disease . Values >2 .8 have been found only in pts w/Graves' disease .

TIBC; SEE IRON-BINDING CAPACITY TISSUE TRANSGLUTAMI NASE ANTI BODY Nl: (-) Present in: celiac disease (specificity, 94%-97%; sensitivity, 90%-98%) , dermatitis

herpetiform is.

TRANSFERRI N Nl range: 1 7 0-370 mg/d l. t: iron deficiency anemia, oral contraceptive admin istration, viral hepatitis, late pregnancy. !: nephrotic syndrome, l iver disease, hereditary deficiency, protei n malnutrition, neoplasms, chronic inflammatory states, chronic i l l ness, thalassemia, hemochromatosis, hemolytic anemia.

TRIGLVCERIDES Nl range: < 1 50 mg/d l. t: hyperl ipoproteinemias (types I, l i b , I l l , IV, V) , diet high in saturated fats, hypothyroidism, pregnancy, estrogens, pancreatitis, EtOH i ntake, nephrotic syndrome, poorly controlled D M , sedentary l ifestyle, glycogen storage disease. !: malnutrition, vigorous exercise, congenital abetalipoproteinemias, drugs (e.g. , gemfi brozil, fenofi brate , nicoti nic acid, metform i n , clofi brate).

TRI IODOTHYRONINE; SEE T3 (TRIIODOTHYRON I N E) TROPONINS (SERUM) Nl range: 0-0 .4 ng/m l ([-) ) . If there is c l i nical suspicion of evolving acute Ml or

ischemic episode, repeated testing i n 5 to 6 hr is recommended. lndetenninate: 0 . 05-0.49 ng/m l. Suggest further tests . I n a pt w/unstable

a ngina and this troponi n I leve l , there is an T in risk of a cardiac event in the near future. High probability of acute Ml: :e:0.50 ng/m l. • cTnT i s a h ighly sensitive marker for myocardial inj u ry for the fi rst 48 h r after Ml and for up to 5 to 7 days. It may also be T in renal fai l u re, chronic m uscle disease, and trauma. • cTn l is h ighly sensitive and specific for myocardial injury (:e:CK-MB) in the i n itial 8 29 hr, peaks with i n 24 hr, and lasts up to 7 days. With progressively h igher levels of cTn l , the riskhttp://medical.dentalebooks.com of mortal ity T because the amount of necrosis T.

t: in addition to ACS , many diseases such as sepsis, hypovolemia, AF, CHF, PE, myocarditis, myocardial contusio n , and renal fai l ure can be associated w/ an l in troponin leve l .

TSH ; SEE THYROID-STI MULATING HORMONE (TSH) TT; SEE THROMBIN TIM E UNCONJUGATED BILIRUBIN; SEE BILIRUBIN, INDIRECT UREA NITROGEN Nl range: 8- 1 8 mg/d l. l: dehydratio n , renal disease (G N , pyelonephritis, diabetic nephropathy) , urinary

tract obstruction (prostatic hypertrophy) , d rugs (AGs and other abx, d i u retics, l ith i u m , corticosteroids), Gl bleedi ng, ! renal blood flow (shock, CHF, M l ) . .1.: l iver disease , malnutrition, third trimester of pregnancy.

URIC ACI D (SERUM) Nl range: 2-7 mg/dl. l: hereditary enzyme deficiency (hypoxanthine-guanine phosphoribosyltransferase),

renal fai l ure, gout, excessive cell lysis (chemotherapeutic agents, rad iation Rx, leukemia, lymphoma, hemolytic anem ia) , acidosis, myeloprol iferative disorders, diet high in purines or prote i n , drugs (diuretics, low doses of ASA, ethambuto l , nicoti nic acid) , lead poisoning, hypothyroidism . .1.: drugs (al lopurinol, febuxostat, h igh doses of ASA, probenecid , warfari n , corticosteroid), deficiency o f xanth ine oxidase, S IADH , renal tubular deficits (Fancon i ' s syndrome) , alcoholism, l iver d isease , diet deficient in prote i n or purines, Wilson 's disease , hemochromatosis.

URINALYSIS Nl range:

• Color: l ight straw • Appearance: clear • pH: 4 . 5-8.0 (average, 6 . 0) • Specific gravity: 1 . 005- 1 .030 • Prote i n : absent • Ketones: absent • Gl ucose: absent • Occult blood : absent

Microscopic examination:

• RBC: 0-5 (h igh-power field) • WBC : 0-5 (h igh-power field) • Bacteria (spun specimen) : absent • Casts: 0-4 hyaline (low-power field)

URINE AMYLASE Nl range: 35-260 U Somogyi/h r. t: pancreatitis, carci noma of the pancreas.

URINE BILE Nl: absent. Abn:

• U rine bil irubi n : hepatitis (vira l , toxic, drug i nd uced) , biliary obstruction . • U rine urobili nogen: hepatitis (vi ral , toxic , drug i nduced) , hemolytic jaundice, l iver cell dysfu nction (cirrhosis, i nfection, mets) .

URINE CALCIUM N l : 6 . 2 mmol/d l (CF, 0 . 02495; SMI, 0 . 1 mmol/d l) . t: primary hyperparathyroidism, hypervitami nosis D, bone mets, M M , l i n Ca intake ,

steroids, prolonged i m mobil ization, sarcoidosis, Paget' s disease , idiopath ic hypercalciuria, renal tubular acidosis . .1.: hypoparathyroidism , pseudohypoparathyroidism, vitamin D deficiency, vita m i n D-resistant rickets, diet l o w i n Ca , drugs (th iazide diuretics, oral contraceptives) , familial hypocalciuric hypercalcemia, renal osteodystrophy, K+ citrate Rx.

URINE cAMP

30 l: hypercalciuria, familial hypocalciuric hypercalcemia, primary hyperparathyroidism, pseudohypoparathyroidism, rickets . .1.: vita m i n D intoxication, sarcoidosis. http://medical.dentalebooks.com

URINE CATECHOLAMINES Nl range: < 1 00 � 2 4 hr (norepi nephrine) ; < 1 0 � 2 4 h r (epinephrine). t : pheochromocytoma, neuroblastoma, severe stress .

URINE CHLORIDE Nl range: 1 1 0-250 m Eq/day. t: corticosteroids, Bartter's syndrome, d i u retics, metabolic acidosis, severe

hypokalemia. !: ch loride depletion (vom iti ng) , colonic villous adenoma, chronic renal fail ure, renal tubular acidosis.

URINE CREATI NINE (24-HOUR) Nl range: 0 . 8- 1 . 8 g/day (male) ; 0 . 6- 1 . 6 g/day (female) .

Note : Useful test as an ind icator of completeness of 24-hour urine collection.

URINE CRYSTALS Uric acid: acid urine, hyperuricosuria, uric acid nephropathy. Sulfur: abx conta i n i ng su lfa . Calcium oxalate: ethylene glycol poisoning, acid urine, hyperoxal uria . Calcium P04-3 : alka l i ne urine. Cystine: cysti n uria .

URINE EOSINOPHILS Nl: absent. Present in: i nterstitial nephritis, ATN , UTI , kidney transplant rejection, HRS.

URINE G LUCOSE (QUALITATIVE) Nl: absent. Present in: DM, renal glycosuria (1 renal threshold for gl ucose) , glucose intolerance.

URINE HEMOGLOBIN, FREE Nl: absent. Present in: hemolysis (w/satu ration of serum haptoglobi n binding capacity and renal

th reshold for tubular absorption of Hgb) .

URINE H EMOSIDERIN Nl: absent. Present in: P N H , chronic hemolytic anemia, hemochromatosis, blood transfusion,

thalassemias.

URINE 5-HVDROXVIN DOLEACETIC ACI D (URI NE 5-HIAA) Nl range: 2-8 mg/24 hr. t: carcinoid tumors, after i ngestion of certain foods (bananas, plums, tomatoes,

avocados, pi neapples, eggplant, wal n uts) , drugs (MAOis, phenaceti n , methyldopa, glycerol guaiacolate, acetaminophen , sal i cylates, phenoth iazines, i m i pramine, methocarbamol, reserpine, methamphetamine).

URINE INDICAN Nl: absent. Present in: malabsorption resulting from intesti nal bacterial overgrowth.

URINE KETONES (SEMIQUANTITATIVE) Nl: absent. Present in: DKA, alcoholic ketoacidosis, starvation , isopropanol ingestion.

URINE M ETANEPHRINES Nl range: 0-2 . 0 mg/24 hr. t: pheochromocytoma, neuroblastoma, drugs (caffeine, phenoth iazines, MAOis), stress.

URINE MYOG LOBIN Nl: absent. Present in: severe trauma, hyperthermia, polymyositis or dermatomyositis, CO

poisoning, drugs (narcotic and am phetamine toxicity) , hypothyroidism, muscle ischemia.

URINE N ITRITE Nl: absent. Present in: UTis.

http://medical.dentalebooks.com

31

URINE OCCULT BLOOD Nl: ( ) (+) in: trauma to urinary tract, renal disease (GN, pyelonephritis) , renal or -

ureteral calc u l i , bladder lesions (carcinoma, cystitis) , prostatitis, prostatic carci noma, menstrual conta m i nation, hematopoietic disorders (hemophilia, thrombocytopenia) . anticoagulants, ASA. N ote: Hematuria w/o eryth rocyte casts or sign ificant albumin uria suggests the pos­ sibil ity of renal or bladder cancers.

URINE OSMOLALITY Nl range: 50- 1 2 00 mOsm/kg. t: SIAD H , dehydration , glycosuria, adrenal i nsufficiency, h igh-protei n diet. !: diabetes insipidus, excessive water i ntake , IV hydration w/D 5W, acute renal insufficiency, G N .

URINE p H N l range: 4.6-8 . 0 (average 6 . 0 ) . t : bacteriuria, vegetarian diet, renal fai l u re w/i nabil ity t o form a m m o n i a , drugs (abx,

NaHC0 , acetazolamide) . 3 !: acidosis (metabolic, respi ratory) . drugs (am mon i u m chloride, methenamine mandelate), D M , starvation, diarrhea.

URINE P0 4" 3

Nl range: 0 . 8-2 . 0 g/24 hr. t: ATN (diuretic phase), chronic renal disease, uncontrolled DM, hyperparathyroidism, hypomagnesemia, metabolic acidosis, metabolic alkalosis, neurofibromatosis, adult­ onset vitamin D-resistant hypophosphatemic osteomalacia. !: acromegaly, ARF, ! dietary intake , hypoparathyroidism , respi ratory acidosis.

URINE K+ Nl range: 25- 1 00 m Eq/24 hr. t: aldosteronism (primary, secondary) . glucocorticoids, a l kalosis, renal tubular

acidosis, excessive dietary K+ intake . !: ARF, K+-sparing d i u retics, diarrhea , hypokalemia.

URI N E PROTEI N (QUANTITATIVE) Nl range: < 1 50 mg/24 hr. t: renal disease (glomerular, tubular, interstitial). CHF, HTN , neoplasms of renal

pelvis and bladder, MM, Waldenstrom's macroglobulinemia.

URI N E NA+ (QUANTITATIVE) Nl range: 40-220 m Eq/day. t: diuretic administration, h igh Na+ i ntake, salt-losing neph ritis, ATN , vomiti ng, Addison's disease, SIAD H , hypothyroidism, CHF, hepatic fai l u re, chronic renal fai l u re , Bartter's syndrome, gl ucocorticoid deficiency, i nterstitial nephritis (caused by analgesic abuse, mannitol , dextra n , or glycerol Rx) , m i l k-al ka l i syndrome , ! ren i n secretion, postobstructive diuresis. !: l in aldosterone, glucocorticoid excess, hyponatremia, prerenal azotemia, ! salt intake.

URINE SPECIFIC CRAVITV Nl range: 1 . 005- 1 . 0 3 . t : dehydratio n , excessive fl uid losses (vomiting, diarrhea , fever) . x-ray contrast media, D M , C H F , SIAD H , adrenal insufficiency, ! fluid intake . !: diabetes insipidus, renal disease (GN, pyelonephritis) , excessive fl uid i ntake or IV hydration.

URINE VAN I LLVLMANDELIC ACI D (VMA) Nl range: the transition at around V3 or V4, and the "septal" q wave and large R wave in lead V5. (From Goldman L, Schafer A1 {edsj: Goldman 's Cecil Medicine, 24th ed. Philadelphia, Saunders, 2012.) FICURE 3-2.

http://medical.dentalebooks.com

Superior

Superior

�

- 1 2o• o• 6o• - ° - 1 50° 0 3 :!: 1 80° + 1 50° 3 60 � : + 90° -

LA

RA

LL Right

Left

I nferior

A

FIGURE 3 - 3 .

B

Right

-

o·

� j ) · · �· �

II

g

�

I nferior

Left

Axis of electrical activation. A, Vectors for the limb leads (LL) in the frontal

plane. B, Hexaxial reference for determining the frontal plane axis. Note that the vectors for the leads I, IT, and ITI are in the same direction as in A, but now, like the augmented limb leads, these standard limb lead vectors have been moved so that they emanate from the center of the figure. (From Goldman L, Schafe-r AI [eds]: Goldman 's Cecil Medicine, 24th ed. Philadelphia, Saunders, 2012.)

i i i . 3 = 1 00 bpm iv. 4 = 75 bpm v. 5 = 60 bpm vi . 6 = 50 bpm b. Determine the heart rhythm. i . Is the rhythm regular? i i . Are there P waves (Fig. 3-4)? iii. Is the P wave related to the ORS ( i . e . , are P waves " married " to the ORS)? iv. The P wave should a lways be u pright i n lead II if there is sinus rhythm ( u n l ess there is reversa l of leads or dextrocard ia). Normal P wave d u ration is half a large box. If the ORS is wide , eva l uate for BBB (Table 3- 1 ) .

QRS associated with the atrial rhythm

------- ------. No (dissociated from

Yes

/--...� ..._

/� Always

Normal P waves precede QRS complexes

Usually or sometimes aroxysmal AV block AV dissociation with capture Abnormal P waves

I

Sinus rhythm with intact AV condition

the atrial rhythm)

Accelerated junctional rhythm Accelerated ventricular rhythm Ju nctional tachycardia Ventricular tachycardia Complete AV block

Atrial activation antegrade Ectopic atrial rhythm M ultifocal atrial tachycardia

��

QRS rate exceeds sinus rate

Accelerated junctional rhythm or tachycardia Accelerated ventricular rhythm or tachycardia

�

Atrial activation retrograde (1 :1 ventriculoatrial conduction) Paroxysmal AV block Junctional rhythm Reentrant supraventricular rhythm

QRS rate below sinus rate

t

Complete AV block

I

Abnormal QRS duration or morphology

Junctional rhythm with i ntraventricu lar aberration Ventricular rhythm

Normal QRS duration or morphology Junctional rhythm

FIGURE 3 - 5 . The QRS rhythm. (From Goldman L, AusieUo D [edsj: Cecil Textbook of Medicine, 22nd ed. Philadelphia, Saunders, 2004.)

TABLE 3- 1

QRS Duration

Axis

LAFB

1 . 3 : 1 ; 30 % of pts wi l l manifest systolic anterior motion of the anterior leaflet of the m itral va lve, causing obstruction of the LVOT. Stress echo can unmask outflow obstruction . • M R I useful in identifying segmental LVH undetectable by echo • CXR: n l or cardiomegaly • ECG (abnl i n 7 5%-95% pts) : LVH , abnl 0 waves i n anterolateral and i nferior l eads • 24-hr Holter mon itor to screen for potential lethal arrhyth mias (pri ncipal cause of syncope or sudden death i n HCM) Major Risk Factors for Sudden Death

• • • • • • •

Spontaneous VT VF, cardiac arrest + Fam ily hx of sudden death U nexplained syncope HF & di lated cardiomyopathy with EF :535%, NYHA class II or I l l symptoms ! i n systolic BP with exercise or blunted l (90%) EPS: to identify delayed potentials that can lead to tachycard iac events CMR: most sensitive method to detect ARVD, but l false + rates: thinning and aneurysmal d ilation of the RV anterior wal l and outflow tract Echo: RV d i latation with regional wal l motion abnlities

Treatment • •

•

• •

•

Avoidance of activity that may trigger tachycardia Right ventricu lotomy Card iac transplantation Antiarrhyth mic Rx with sotalol, am iodarone, propafenone, �-blocker alone or in combi nation can be used Radiofrequency ablation is used i n cases of refractory VT, frequent tachycardia after defibril lator placement, or local ized arrhyth mia sites. I mplantable cardioverted defibrillators hold promi se

1J TAKOTSUBO CARDIOMYOPATHY (STRESS CARDIOMYOPATHY, SC) The term takotsubo is the Japanese name for an octopus trap (takotsubo), which has a similar shape of the LV in systole during a left ventriculogra m . Diagnosis

Mayo C l i n ic criteria (2008) : Al l 4 criteria are required to make Dx. 1 . Transient hypoki nesis, akinesis, or dyskinesis of the left ventricular mid segments with or without apical involvement. The RWMA typically extend beyond a si ngle epicardial coronary distribution. A stressful trigger is often but not always present. 2. Absence of obstructive CAD or angiographic evidence of acute plaque rupture 3 . New ECG abnormalities: either ST-segment l and/or T wave i nversion or modest l in cardiac troponin 4. Absence of pheochromocytoma or myocarditis Imaging •

•

•

Echo: may show apical ballooning Cardiovascular M R I Cardiac cath : T h e I t ventriculogram is diagnostic.

Treatment •

•

•

•

�-blockers, ACEis, and diuretics for systolic dysfunction Pts in shock without significant LVOT: Rx with IAB P Repeat Echo (in 4 to 6 wk) to ensure n l ization of systolic function (most pts nl ize by this time) Duration of medical Rx is debatable.

H. MYOCARDITIS

94 Inflammatory disorder of the myocard i u m Etiology

•

Infection, drugs, collagen-vascular disorders, rad iation, post partum

Suspected myocarditis Clinical symptoms :!: chest pain , S T elevation, troponin + , echocardiography

•

I PCI/CABG I

Consider coronary angiography. Is it coronary atherosclerosis?

Yes

No

•

Diagnosis equivocal

•

•

I

Clinical suspicion high: G iant cell myocarditis Sarcoidosis (focal LGE) Allergic myocarditis

Cardiac M R T1 and T2 relaxation times Late gadolinium enhancement (LGE)

Myocardial edema Subepicardial or midwall LG E

t

No LG E : consider stress-induced or takotsubo cardiomyopathy

•

Myocard itis Consider CMR targeted EM biopsy Viral genome PCR lmmu nostaining on EM biopsy specimen

I

t

I Consider EM biopsy I •

Transm u ral or subendocardial LG E conform ity to vessel distribution

I·

t

Ischemic injury Vasospasm/embolic infarction

I

Immunosuppressive Rx cardiac transplantation

I

•

Supportive Rx

FICURE 3-2 5 . Diagnostic algorithm for suspected acute myocarditis. (Adapted from Nelson KH, Li T, Afonso L. Diagnostic approach and role of the assessment of acute myoca1·ditis. Cardiol Rev 1 7:24-30, 2009.)

Diagnosis H&P •

• •

• • • •

Persistent tachycardia out of proportion to fever Faint S 1 , 54 sound on auscultation M u rmur of M R Pericardia! friction rub i f associated w/pericarditis S igns of biventricular fai l u re (hypotension , hepatomegaly, peri phera l edema, distention of neck veins, 53) H/o recent i nfl uenza-l ike syndrome (fever, arthralgias, malaise) , dyspnea (72%), chest pain (32%), arrhythmias ( 1 8%) W/up (Fig. 3-25)

Treatment •

Rx of underlying cause, supportive care , Rx of systolic HF (if present)

I. DISEASES OF THE AORTA 0 THORACIC AORTIC AN EURYSM Risk Factors

•

• •

Heritable • Marfa n ' s (lens dislocation, arm span > height, tal l , scol iosis, arachnodactyly, MVP, pectus cari natum, thumb and wrist signs) • Ehlers-Danlos Ooint hypermobil ity, thin transl ucent ski n) • Loeys-Dietz (craniosynostosis, cleft palate, hypertelorism) • Fam ilial TAAD Degenerative: HTN , smoking, atherosclerosis Other: Takayasu ' s arteritis, untreated syph ilis

95

DeBakey types II

Ill

Tear

Type A

Type B Stanford types

FICURE 3-26. Classification of aortic dissection. (F'rom Weisslede?· R, Wittenberg J, Harisinghani MG, Chen JW· Primer of Diagnostic Imaging, 5th ed. St. Louis, Mosby, 201 1 .)

Diagnosis •

•

Most detected i ncidental ly; compressive sx (hoarseness, stridor, dysphagia) If phenotypic expression of genetic disease recognized , aortic imaging warranted

Imaging •

•

•

Echo: good for aortic root/proximal aorta, poor for aortic arch M R I : good for entire aorta CT: good for entire aorta but radiation and contrast dye exposure

Treatment •

•

•

•

BP control (�-blockers, ACEis, particularly useful in Marfa n ' s) Stop smoking CT or MRI annually Repair if � 5 . 5 em for degenerative disease, �5 em for Marfa n ' s , >4. 5 em for other heritable causes. However, rapid expansion (>0.5 cm/yr) may b e a n indication for repair regardless of absolute diameter.

D ACUTE AORTIC SYNDROMES (AORTIC DISSECTION, INTRAMURAL H EMATOMA, PENETRATING ATH EROSCLEROTIC ULCER) • •

•

Dissection: I ntimal tear allows blood to dissect between medial layers of the aorta . Intramural hematoma: secondary to microtears in intima or rupture of vasa vasorum Penetrating atherosclerotic ulcer: HTN + atherosclerosis plaque rupture and =

pseudoaneurysm

Classification

Based on the location of d issection (Fig. 3-26) DeBakey: type I , ascending and descending aorta; I I , ascending aorta; I l l , descendi ng aorta • Stanford : type A, ascending aorta (proxi mal); type B, descending aorta (distal) •

Diagnosis H&P •

• •

Sudden onset of severe chest pai n often descri bed as sharp, tearing, or ripping. Pain can be a nterior w/ascending aortic dissection or back pain w/descending aortic dissection. Pulse and BP differentials common (38%). caused by partial com pression of subclavian arteries Most pts present w/severe HTN . Hypotension (2 5%) can indicate bleedi ng, cardiac tamponade, or severe AI .

Imaging

96

•

• •

TEE: study of choice i n unstable pts. Sensitivity is 97% to 1 00%. MRI: gold standard and gives best information to surgeons. Sensitivity is 90% to 1 00%, but length of test and difficult access are not suitable for stable intubated pts. CXR: may show widened mediasti num (62%)

Treatment •

•

• • •

•

Target SBP < 1 20, H R 1 0 mm depth , or associated i ntram ural hematoma] or progressive di latation despite med Rx) Evolving role for endovascular repai r as less i nvasive

D ABDOMI NAL AORTIC AN EURYSM Diagnosis Imaging •

•

Abd U/S : preferred i n itial imaging modal ity; esti mates size within 0 . 4 e m ; not very good i n estimating proxi mal extension to renal arteries or i nvolvement of i l iac a rteries CT scan and angiography: more accurate , used preoperatively

Causes • •

• •

•

•

Atherosclerotic (degenerative or nonspecific) : risk factors are older age, smoking, male sex, wh ite race, FHx AM, occl usive atherosclerotic disease Genetic (e.g. , Ehlers-Danlos syndrome) Trauma Cystic medial necrosis (Marfa n ' s syndrome) Arteritis, i nflammatory Mycotic, syphilitic

Treatment •

• •

Mon itoring by U/S or CT q 6 mo for AA measuring >4.5 e m . In pts w/AM 3 . 5 to 4 . 4 e m , mon itor yearly; 3 . 0 to 3 . 4 e m , q 3 yr; and 80%. • 70% of AMs are asym ptomatic. U/S of AA to screen for AM. Consider in all male smokers 65 to 7 5 y.o.

J. ARRHYTHMIAS 0 AV CONDUCTION DEFECTS a. First-degree heart block

•

•

•

•

PR interval >200 msec Delay in impulse cond uction i n AV node No Rx needed Asymptomatic but small t risk of AF and need for pacer over long term

b. Second-degree heart block

Types of second-degree AV block: • Mobitz type I (Wenckebach) (Fig. 3-27) • Progressive prolongation of the PR interval before an impu lse is completely blocked. The cycle repeats period ically. • Cycle w/dropped beat is 0.44 sec associated w/ l risk of l ife-th reaten i ng ventricular arrhythmias, most common channelopathy (1 : 5 , 000)

Etiology •

•

•

Cardiac repolarization abnormal ity Congen ital cause (chromosome 3 or chromosome 7 abnormal ity) Acq uired causes: • Drugs (dofeti lide, ibutilide, bepridil, quinidine, procainamide, sotalol , amiodarone, ranolazine, disopyramide, phenoth iazines and antiemetic agents [droperido l , domperidone]. tricyclic antidepressants, quinolones, azithromycin, methadone, astem izole or cisapride given w/ketoconazole or erythromycin, clarithromycin, and antimalarials) , particularly among pts w/asthma or those using hypokalemic meds • Hypokalemia, hypomagnesemia, hypocalcemia • Liquid protein diet • CNS lesions • MVP • Hypothyroidism

Diagnosis H&P •

•

•

•

•

•

Palpitations, presyncope Syncope caused by VT Sudden death Familial (associated w/deafness) : a utosomal recessive Familial associated w/n l hearing: a utosomal domi nant (incidence unknown) Although inheritance of LOTS is autosomal domi nant, female predomi nance has often been observed and has been attributed to a suscepti bil ity to cardiac arrhythmias i n women.

109

TABLE 3-29 • ECC Criteria for Congenital Long QT Syndrome

Corrected OT >480 msec Corrected QT 460-480 msec Corrected QT 450-460 msec (men) Torsades de pointes T wave alternans Notched T wave i n 3 leads Bradycardia

3 points 2 points 1 point 2 points 1 point 1 point 0 . 5 point

History

Syncope w/stress Syncope w/o stress Congenital deafness Defin ite FHx of long OT Unexplained cardiac death i n first-degree relative age 460 msec, torsades de poi ntes. Diagnostic criteria for the congenital LOTS are given i n Table 3-29.

Treatment •

•

•

Asymptomatic sporad ic forms w/no complex ventricular arrhythmias: no Rx Risk stratification • H igh risk (>50o/o of cardiac event) : OTc >500 msec and LOT l and LOT2 or male pt w/LOT3 • Moderate risk (30o/o-50o/o) : OTc >500 msec in female pt w/LOT3 or OTc 5 0 msec ORS Axis

Axis shift of >40 degrees between N S R and WCT Right superior (northwest) axis Left axis deviation with RBBB morphology Right axis deviation with LBBB morphology Precordial ORS Concordance

Positive concordance Negative concordance QRS Morphology in RBBB Pattern WCT

Monophasic R. biphasic qR complex. or broad R (>40 msec) in lead V1 Rabbit ear sign: double-peaked R wave i n lead V1 with the left peak taller than the right peak rS complex in lead V6 Contralateral BBB in WCT and NSR

QRS Morphology in LBBB Pattern WCT

Broad initial R wave of �40 msec in lead V1 or V2 R wave in lead V1 during WCT taller than the R wave during NSR Slow descent to the nadir of the S , notching i n the downstroke of the S wave in lead V 1 RS interval > 70 msec in lead V1 or V2 0 or OS wave in lead V6 From lssa Z, Miller J M , Zipes DP: Clinical Arrhythmology and Electrophysiology, 2nd ed. Philadelphia, Saunders, 20 1 2 .

FIGURE 3-42.

Torsades de pointes. (From Cerra FB: Manual of Critical Care. St. Louis,

Mosby, 1 998.)

Treatment • •

Electrical term i nation of the tachycard ia w/cardioversion when the ventricular tachyarrhyth mia is sustai ned lCD

K. PERIPHERAL ARTERIAL DISEASE (PAD) Stenotic, occl usive, and aneurysmal diseases of the aorta and its branch arteries, excl usive of the coronary arteries. The primary cause of PAD is atherosclerosis. Diagnosis •

•

•

1 12

Based on the presence of l i m b sx or a low an kle-brachial i ndex (AB I) :50.90 The ABI is calculated by dividing the h ighest ankle systolic pressure in either the dorsa lis pedis or posterior tibial a rtery by the h ighest systolic pressu re from either arm . The severity o f PAD is based o n the ABI a t rest and d uring tread m i l l exercise ( 1 -2 mph, 5 m i n , or sx l i m ited): • M i l d : ABI at rest 0 . 7 1 to 0 . 90 or ABI d u ring exercise 0 . 5 0 to 0.90 • Moderate : ABI at rest 0.41 to 0 . 7 0 or ABI d u ring exercise 0 . 2 0 to 0 . 50 • Severe : ABI at rest 400

1 0 units, call physician

1 3 units, call physician

1 8 units, call physician

250 mg/dl; urine and serum ketones (+) (usually 7- 1 0 mmoi/L) . ABGs reveal acidosis: arterial pH usually 40 mm Hg. Serum electrolytes: • Serum bicarbonate is usually < 1 8 m Eq/L. • Serum K+ : may be l, n l , or T. There is always sign ificant tota l body K+ depletion regardless of the K+ leve l . • Serum Na+: usually l (pseudohyponatremia) a s a result of il glucose, dehydration, and lipemia. Assume 1 .6 mEq/L l in extracellular Na+ for each 1 00 mg/dll in glucose. • Calculate the AG : AG Na+ - (CI - + HC0 3 -) . • I n DKA, the AG is l (generally > 1 5) ; hyperch loremic metabolic acidosis may be present i n u n usual circumstances when both the GFR and the plasma volume are well maintained. =

Adult patient with DKA or HHS

I

+ Complete initial evaluation, including (but not limited to):

Medical history and physical examination Complete blood count with diffe rential Fingerstick blood glucose Serum chemistries ("Chem- 1 0" plus serum ketones)

U rine for urinalysis and ketones Cultures as indicated (wound, blood , urine, etc.) Chest :!: abdominal x-ray 1 2-lead EGG

+ IV Fluids Based on corrected serum sodium* If h igh/normal, use 0.45% NaCI If low/normal, use 0.9% NaCI Conti nue IV fluids at 250-1 000 mUhr, depending on volume status, cardiovascular history, and cardiovascular status (pulse, BP)

__,

Concurrently, beg in empi rical fluid resuscitation with 0.9% NaCI at 1 000 mUhr Consider volume expanders if hypovolemic shock is present Conti nue fluid resuscitation u ntil volume status and cardiovascular parameters (pulse, BP) have been restored

y Insulin Therapy Regular insulin bolus, If serum glucose 0. 1 5 U/kg falling too rapidly, IV infusion, 0. 1 0 U/kg/hr back off on insulin i nfusion Check serum glucose hourly-should fall If serum glucose by 50-80 mg/dUhr rising or falling too slowly, increase insulin infusion rate by 50-1 00%

Continuing Management: Fol low and replete serum electrolytes (including d ivalent cations) q2-4h until stable After resolution of hyperglycemic state, follow blood glucose q4h and initiate sliding scale regular insulin coverage Convert IV insulin to subcutaneous injections (or resumption of prior therapy) , ensuring adequate overlap

-

Begin clear liquid diet and advance as tolerated. Encourage resumption of ambu lation and activity Review and update diabetes education, with special attention to prevention of further hyperglycemic crises

When serum glucose reaches 250-300 mg/dl: For DKA, add dextrose to IV fluids and reduce insulin infusion, adj usted to maintain serum gl ucose - 200 mg/dl until anion gap has closed For HHS, continue IV fluids but may reduce insulin infusion until plasma osmolal ity d rops below 3 1 0 mOsm/kg Begin more exhaustive search for precipitant of metabolic decompensation

y Potassium (K + ) Repletion Obtain baseline serum potassium; Obtain 1 2-lead EGG [K + ] ;:,:5.5 m Eq/L [K + ] 4. 1 �giL. Normal response is GH >3 �L. If hypoglycemia occurs [glucose 7 �dL or to >20 �dl. I n most normal individuals, the basal ACTH increases twofold to fou rfold and reaches a peak [201 00 pg/mL). ACTH responses may be delayed i n cases of hypotha­ lamic dysfunction. Cortisol levels usually reach 20-25 �dl. A normal response is 1 1 -deoxy­ cortisol >7 .5 �dL or ACTH >75 pg/m l. Plasma cortisol should fall below 4 �dL to ensure an adequate response. A normal response is cortisol > 1 8 �dl. I n suspected hypothalamic­ pituitary deficiency, a low-dose [ 1 -�) test may be more sensitive . Low free thyroid hormone levels in the setting of TSH levels that are not appropriately increased. Basal LH and FSH should be increased in postmenopausal women. Low testosterone levels in conjunction with low or low­ normal LH and FSH are consistent with gonadotropin deficiency. I n most normal persons, LH should increase by 1 0 I U/L and FSH by 2 I U/L. Normal responses are variable, and repeated stimu­ lation may be required. A 50% increase should occur in LH and FSH , usually by day 5 .

Combined or i ndividual releasing hormone responses must be evaluated in the context of basal hormone values and may not be diagnostic [see text) .

From Goldman L, Schafer AI (eds): Goldman's Cecil Medicine, 24th ed. Philadelphia, Saunders, 20 1 2 . *Values are with polyclonal assays. •

•

•

TSH deficiency: levothyroxine 0 . 0 5 to 0 . 1 5 mg/day GH deficiency: GH is generally not used in adults; however, it can be given at 0 . 04 to 0 . 08 mg/kg/day SC i n chi ldren . ADH deficiency: Desmopressin (DDAVP) 1 0 to 20 � by i ntranasal spray or 0 . 0 5 to 133 0. 1 mg PO bid is used i n pts w/D I .

D ANTERIOR PITUITARY HVPERFUNCTION SECONDARY TO PITUITARY NEOPLASMS •

Pitu itary adenomas are classified b y t h e i r size (macroadenomas � 1 0 mm) a n d fu nction • G H-+ acromegaly • PRL--+ prolacti noma • ACTH-+ Cushing's disease

H&P Prolactinomas •

• •

Females: galactorrhea, amenorrhea, ol igomenorrhea with anovulation, infe rti l ity Estrogen deficiency lead ing to h i rsutism, ! vagi nal l ubrication , osteopenia Males: ! l i bido or hypogonadism

GH-Secreting Pituitary Adenoma: Acromegaly •

•

Coa rse facial features, oily ski n , prognathism, carpal tunnel syndrome Osteoarthritis, hx of l hat, glove, or shoe size, visual field deficits

Corticotropin-Secreting Pituitary Adenoma: Cushing 's Disease •

• •

Truncal obesity, round facies (moon face) Dorsocervical fat accumulation (buffalo hump) , h i rsutism, acne, menstrual disorders HTN , striae, bruising, thin ski n , hyperglycemia

Thyrotropin-Secreting Pituitary Adenoma •

Sx: thyrotoxicosis, goiter, visual impai rment

Diagnosis Prolactinoma •

•

l PRL levels are correlated with tumor size. Level >200 ng/m L is diagnostic, with levels of 1 00 to 200 ng/mL being equivocal .

Acromegaly • •

•

•

Fi rst screening tests are the measurement of serum IGF- 1 l, postprandial serum GH, and TRH sti m ulation test. Fol low with an OGTI. Fai l u re to suppress seru m GH to 300 ng/m L is indicative of an ectopic source of G H .

Cushing 's Disease •

•

•

•

•

Nl or sl ightly l corticotropin levels ranging from 20 to 200 pg/m L Level < 1 0 pg/m L usually indicates an autonomously secreti ng adrenal tumor. Level >200 pg/m L suggests an ectopic corticotropi n-secreting neoplas m . Cushing's disease c a n be assessed b y absence o f cortisol suppression with the low-dose dexamethasone test but with the presence of cortisol suppression after the high-dose test. 24-hr urine collection should demonstrate an l level of cortisol excretion.

Thyrotropin-Secreting Pituitary Adenoma • • •

•

H ighly sensitive thyrotropin assays, wh ich eva l uate the presence of thyrotoxicosis, are among the ways to detect a thyrotropi n-secreting tumor. Free a subunit is secreted by >80% of tumors, with the ratio of the a subunit to thyrotropin < 1 . With central resistance to thyroid hormone, the ratio is < 1 . l seru m levels of both T 3 and T4

Imaging •

•

M R I of the pitu itary and hypothalamus CT scan only when M R I is unavailable or is otherwise contraindicated

Treatment Surgery • • •

Selective transsphenoidal resection of the adenoma is used for acromegaly, Cushing's disease, and thyrotropin-secreting pituitary adenomas. Rad ioRx is reserved for pts who have not responded to surgical Rx and who sti ll have sx of the adenoma. Bilateral adrenalectomy is performed i n pts with Cushing's disease after fai l u re of other therapies; complications requ i ring l ifelong hormone replacement or Nelson ' s syndrome m a y occur.

RadioRx •

•

Generally reserved for pts who have not responded to surgical Rx Used with varying degrees of success i n all the different pituitary adenomas

1 34 Medical

Prolacti noma

•

Bromocriptine or cabergoline

Acromega ly •

Octreotide

C u s h i n g ' s D i sease •

•

Ketoconazole, which i n h ibits the cytochrome P-450 enzymes i nvolved i n steroid biosynthesis, is effective i n managing mild to moderate disease in daily ora l doses of 600 to 1 200 mg. Metyrapone and ami nogl utethimide can be used to control hypersecretion of cortisol but are generally used when preparing a pt for surgery or while waiting for a response to radioRx.

Thyrotro p i n-Secreti ng Pitu ita ry Adenoma •

•

Ablative Rx with either rad ioactive iodide or surgery Octreotide

D. FLUID HEMOSTASIS DISORDERS 0 DIABETES INSIPIDUS (DI) Definition

Th is polyuric disorder results from insuffi cient prod uction of ADH (pituitary [centra l , neurogenic] D l ] or unresponsiveness o f t h e renal tubules t o ADH (nephrogenic D l ] . Etiology Central (Neurogenic) Dl •

• •

• •

• •

•

Idiopathic Neoplasms of brain or pituitary fossa (craniopharyngiomas, metastatic neoplasms from breast or l u ng] Post-therapeutic neurosurgical proced ures (e.g. , hypophysectomy] Head trauma (e.g. , basal sku l l fx) Granulomatous disorders (sarcoidosis or TB] H i stiocytosis (Hand-Sch uller-Ch ristian disease , eosinoph i l i c granuloma] Fam i l ia l (autosomal dominant] Other: i nterventricular hemorrhage , aneurysms, meningitis, postencephalitis, M S

Nephrogenic Dl • •

•

•

Drugs: l ith i u m , am photericin B, demeclocycline, methoxyfl urane anesthesia Fam i l i a l : X-l i n ked Metabolic: hypercalcemia or hypokalemia Other: sarcoidosis, amyloidosis, pyeloneph ritis, polycystic disease , sickle cell disease, postobstructive cond ition

Diagnosis H&P •

•

•

•

Polyu ria : urinary vol umes rangi ng from 2 . 5 to 6 Uday Polydipsia (predi lection for cold or iced drinks] Neurologic man ifestations (seizures, headaches, visual field defects) Evidence of volume contractions

Labs

. ! Urine specific gravity (s; 1 . 005] . ! Urine osmolal ity (usually 2 1 yr of age who have not achieved remission after 1 yr of antithyroid drug Rx. Subtotal thyroidectomy is indicated in obstructing goiters, i n any pt who refuses RAI and can not be adeq uately managed w/antithyroid medications (e.g. , pts w/ toxic adenoma or toxic m u ltinodular goiter) , and i n pregnant pts who cannot be adequately managed w/antithyroid medication or develop side effects to the m .

Clinical Pearl •

Elderly hyperthyroid pts may have only subtle signs (weight loss, tachycardia, fine ski n , brittle nails) . This form is known as apathetic hyperthyroidism and is manifested by lethargy rather than with hyperki netic activity. An enlarged thyroid gland may be absent. Coexisting medical disorders (most commonly cardiac disease) may also mask the sx. These pts often have unexplained CHF or new-onset AF.

D THYROI D STORM

Acute life-th reatening exacerbation of hyperthyroidism Diagnosis •

•

•

•

•

Tremor, tachycardia/tachyarrhyth m ias, fever (as h igh as 1 05.8° F) Sweati ng, diarrhea , vasodi latation Lid lag, lid retraction , proptosis, goiter Change in mental status (psychosis, coma, seizures) Other: preci pitati ng factors (i nfection, trauma), CHF, hepatosplenomegaly, jaundice

Labs •

l Free T4, l TS H

Treatment • • •

•

• •

Replace fl uid deficit aggressively (daily fluid requ i rement may reach 6 L) ; use sol utions conta i n i ng glucose and add m ultivitamins to the hydrating solution. Propylthiouracil (PTU) 800 mg initially (PO/NG tube)/PR, then 200 to 300 mg PO/PR q6h (allergy PTU , methimazole 80- 1 00 mg PO/PR followed by 40 mg PO/PR q8h). Inhi bition of stored thyroid hormone from the gland: • Iodide can be administered as Telepaque (iopanoic acid) 1 g PO once daily or Na+ iodine 250 mg IV q6h , or, saturated sol ution of K+ iodide (SSKI ) , 5 gtt PO q8h , or Lugol's solution, 1 0 gtt PO q8h. It is i m portant to administer PTU or meth i mazole 1 hr before the iodide to prevent the oxidation of iodide to iodine and its incorporation i n the synthesis of additional thyroid hormone. • Corticosteroids: Dexamethasone 1 to 2 mg IV q6h or hydrocortisone 1 00 mg IV q6h for approxi mately 48 hr i s useful to i n h i bit thyroid hormone rel ease, impair peri pheral conversion of T3 from T4 · and provide additional adrenocortical hormone to correct deficiency (if present) . Suppression of peri phera l effects of thyroid hormone: �-adrenergic blockers: Administer propranolol 80 to 1 20 mg PO q4 to 6h. Propranolol may also be given IV 1 mg/m i n for 2 to 1 0 min under continuous ECG and blood pressure mon itoring. �-Adrenergic blockers m ust be used with caution in pts with severe CHF or bronchospasm. Cardioselective �-blockers (e.g. , esmolol or metoprolol) may be more appropriate for pts with bronchospasm , but these pts must be closely monitored for exacerbation of bronchospasm because these agents lose their cardioselectivity at l doses. Control of fever with aceta m i nophen 325 to 650 mg q4h ; avoid aspirin because it displaces thyroid hormone from its binding protei n R x o f a n y preci pitating factors (e.g. , a b x if i nfection is strongly suspected)

1J HYPOTHYROI DISM Etiology

•

Primary hypothyroidism >90% of the cases • Hashi moto's thyroiditis: most common cause of hypothyroidism after 8 yr of age • Idiopath ic myxedema (nongoitrous form of Hashi moto ' s thyroid itis) • Previous Rx of hyperthyroidism (rad ioiodine Rx, subtotal thyroidectomy)

139

Rio early hypothyroidism, Hashimoto's thyroiditis, subacute thyroiditis, '-------.--' autoimmune lymphocytic thyroiditis, recovery from severe illness FICURE 5-4.

Diagnostic algorithm for hypothyroidism.

Subacute thyroiditis Radiation Rx to the neck (usually for mal ignant disease) Iodine deficiency or excess Drugs (lith i u m , PAS , sulfonamides, phenylbutazone, amiodarone, thiourea) Congenital (approximately 1 case per 4000 l ive births) Prolonged Rx w/iodides Secondary hypothyroidism : pituitary dysfunction, postpa rtum necrosis, neoplasm , infi ltrative disease causing deficiency of TSH • Tertiary hypothyroidism : hypothalamic disease (granuloma, neoplasm , or irradiation causing deficiency of TRH) • Tissue resistance to thyroid hormone: rare • • • • • • •

Diagnosis H&.P

• Ski n : dry, coarse, thick, coo l , sallow (yel low color caused by carotenemia) ; non pitti ng edema in skin of eyelids and hands (myxedema) secondary to infiltration of SC tissues by a hydroph i l i c mucopolysaccharide substance • Hair: brittle and coarse; loss of outer third of eyebrows • Facies: d u l led expression , thickened tongue, thick, slow-movi ng l i ps • Thyroid gland: may or may not be palpable (depending on the cause of the hypothyroidism) • Heart sounds: distant, possi ble pericardia! effusion • Pulse: bradycardia • Neurologic : delayed relaxation phase of the DTRs, cerebellar ataxia, hearing i m pairment, poor memory, peripheral neuropath ies w/paresthesia • Musculoskeleta l : carpal tunnel syndrome, m uscle stiffness, weakness Labs (see Table 5- 7; Fig. 5-4)

• TSH : l TSH may be n l if pt has secondary or tertiary hypothyroidism, pt is receiving dopamine or corticosteroids, or the level is obtained after severe i l l ness. • l Free T4 • Other common laboratory abnl ities: hyperl ipidemia, hyponatremia, and anemia • Antimicrosomal and antithyroglobulin Ab titers : useful only when a utoimm une thyroiditis is suspected as the cause of the hypothyroidism

Treatment

• Levothyroxi ne 25 to 1 00 !!Wday, depending on pt' s age and severity of the disease. The dose may be l every 6 to 8 wk, depending on the clin ical response and serum TSH leve l . Elderly pts and pts w/CAD should be started w/ 1 2 . 5 to 25 !!Wday (higher doses may precipitate angi na) . Clinical Pearls

• Periodic mon itoring of TSH level is an essential part of Rx. Pts should be evaluated w/office visit and TSH levels every 6 to 8 wk until the pt is clin ically euthyroid and the TSH l evel is normal ized . • For mon itori ng Rx in pts w/central hypothyroidism , measurement of serum free T4 level rather than TSH is appropriate ; it should be mai ntai ned i n the upper half of the nl range . 140 • Pregnant pts also have l requ i rements. Women w/hypothyroidism should generally l their levothyroxine dose by approxi mately 30% as soon as pregnancy is confi rmed and have frequent testi ng.

D SUBCLI N ICAL HYPOTHYROIDISM

• Frequency: 1 0% to 1 5% of elderly • Labs: l serum TS H and a n l free T4 level • Associated with an l risk of CHD events (particularly i n those with a TSH concentration of :e: 1 0 m U/L) • Rx: Levothyroxine if TSH :e: 1 0 m U/L and with presence of goiter or thyroid autoanti bodies

I) MYXEDEMA COMA •

Thi s is a life-th reatening compl ication of hypothyroidism .

Etiology

• Decom pensation of hypothyroidism secondary to • Sepsis • Exposure to cold weather • CNS depressants (sedatives, narcotics, antidepressants) • Trauma, surgery Diagnosis H&.P

• Profound lethargy or coma • Hypotherm ia (rectal temperature 2 em, age 1 0 wk gestation ; or prematu re births before 34 wk gestation secondary to eclampsia, preeclampsia, or severe placental

insufficiency; or th ree or more u nexplained consecutive spontaneous abortions 2 occasions, at least 1 2 wk apart

Treatment + APL w/ venous thrombosis: i n itial anticoagu lation w/hepari n , then l ifelong

•

•

• •

•

warfarin Rx, INR 2.0 to 3 . 0 . Consider h igher target INR (3-4) i n pts with recurrent thromboembolism on warfari n . + APL w/arterial thrombosis • Cerebral arterial thrombosis: ASA 325 mg qd or warfarin • Noncerebral arterial thrombosis: warfarin Catastrophic APS: Combi nation of anticoagu lation, corticosteroids, and IVIG or

plasma exchange Prophylaxis for asymptomatic pts w/+ APL w/o previous thrombosis: • No routi ne prophylaxis is recommended . • Questionable whether ASA 8 1 mg qd is effective • Antithrombotic prophylaxis for major surgery, prolonged i m mobil ization, and pregnancy Note on warfarin or U F H mon itoring: • In pts with APS Ab that artificially T PT/I N R , when using warfari n , mon itor I N R by measuring chromogenic factor X levels. • I n pts with APS ab that T APTI, when using UFH, use anti-Xa assay to monitor UFH or change over to LMWH .

D VENOUS THROMBOEMBOLISM (DVT)

Presence of thrombi in the deep veins of the extrem ities or pelvis

Diagnosis H&P

Pain and swe l l i ng of the affected extrem ity In LE DVT: leg pai n on dorsiflexion of the foot (Homans ' sign) • Exam may be unremarkable in early DVT. • Clin ical pred iction rules can be used to establish pretest probability of DVT. The Wells ' prediction rules for DVT are described in Table 7- 1 0 . These rules perform better in younger pts w/o h/o DVT and in those w/o comorbidities. In younger pts w/o associated comorbidities and a low pretest probabil ity by Wells' criteria and a (-) h igh-sensitivity D-d i mer test result, the dx of DVT can be reasonably excluded.

•

•

Labs • •

Baseline PT ( I N R) , APTI, and Pit count should be obta i ned on all pts before anticoagulation is started. D-dimer assay by ELISA: DVT can be ru led out i n pts who are c l i n ically u n l ikely to have DVT and have a (-) D-dimer test result. D-d i mer can also be combined w/U/S . The combi nation of a n l D-dimer w/a nl com pression venous U/S is usefu l to excl ude DVT and to e l i m i nate the need for repeated U/S at 5 to 7 days. Figure 7-5 describes an algorith m for the Dx of DVT.

TABLE 7- 1 0 • Wells' Clinical Assessment Model for the Pretest Probability

of Lower Extremity DVT

Active cancer (treatment ongoing or withi n previous 6 mo or palliative) Paralysis, paresis, or recent plaster immobilization of the lower extremities Recently bedridden > 3 days or major surgery within 4 wk Localized tenderness along the distribution of the deep venous system Entire leg swollen Calf swelling > 3 em asymptomatic side (measured 1 0 em below tibial tuberosity) Pitting edema confined to the symptomatic leg Collateral superficial veins (nonvaricose) Alternative diagnosis as likely as or greater than that of DVT

Score 1 1 1 1 1 1 1 1 -2

In patients with sym ptoms in both legs, the more symptomatic leg is used. Pretest probability is calculated as the total score: high, >3; moderate, 1 -2 ; low, 90 sec (>3

x

x

40 U/kg as bolus, then infusion rate by 2 U/kg/hr No change

control

control value)

! lnfusion rate by 2 U/kg/hr

Stop infusion for 1 hr, then ! infusion rate by 3 U/kg/hr

2. 5,ooo:u Bolus Dose, followed by 1,280 1!/hr

(1!)

Stop Infusion

Rate of Change

(miJhr)

Repeat APTI'

0

+3

In 6 hr

0

+3

In 6 hr

0

0

0

Next morning

85-95

0

0

-2

Next morning

96- 120

0

30

-2

In 6 hr

> 120

0

60

-

4

In 6 hr

APTI' (see)

Bolus

* 1 10

-6

-5,760

Additional Aetion

Repeat AP'IT in 4-6 hr Repeat AP'IT in 4-6 hr None* Stop heparin for 1 hr; repeat

AP'IT 4-6 hr after restarting heparin Rx

Stop heparin for 1 hr; repeat

AP'IT 4-6 hr after restarting heparin Rx

* If the APTI is subtherapeutic desp ite a heparin dose of at least 1 ,440 U/hr (36 mUhr) at any time during the first 48 hours of therapy, the response to an APTI of 400/m m 3 ) : Diffuse lymphadenopathy may be present. Levels of viral repl ication, 1 09 copies/day, occur at this stage even though the pt remains asym ptomatic. Middle stage (CD4 cells, 2 00-400/m m 3 ) • Mycobacterium tuberculosis infections, recurrent herpes zoster, persistent mucocutaneous herpes simplex infections, and recu rrent bacteremias caused by Streptococcus pneumoniae and Salmonella spp occur. • Kaposi 's sarcoma, oral candidiasis, and hairy leukoplakia appear. AI DS: advanced H IV infection (CD4 cell count 200. Coccidioidomycosis • After i n itial Rx for coccidioidomycosis, l ifelong suppressive Rx is recom mended w/fl uconazole 400 mg PO qd or itraconazole 200 mg PO bid. • Recommendations for disconti n uation of secondary prophylaxis (long-term maintenance Rx) in a pt w/a CD4 count > 1 00 receiving ART are not avai lable. • Fl uconazole and itraconazole have potential teratogenicity in pregnant women . Consider am photericin B (preferred). especially during the first trimester. All H IV(+) women receiving azole Rx for coccidioidomycosis should maintai n b i rth control precautions. H i stoplasmosis • I n itial Rx for d isseminated histoplasmosis is am photericin B for 1 to 2 wk followed by long-term maintenance Rx w/itraconazole 200 mg PO bid. • Discontin uation of long-term maintenance may be considered if the ART-restored C D4 count is >200. • ltraconazole has teratogenicity and embryotoxicity and should not be offered during 229 pregnancy. Rx w/amphotericin B is preferred during the first trimester. H IV-infected women receiving azole Rx should maintai n effective b i rth control measures .

•

Pneumocystis infection • Pts have SOB and nonproductive cough w/few findi ngs on exam; CXR usually

reveals an i nterstitial infi ltrate but may be nl in i n itial stages.

• Dx is usual ly made by sputum induction or by BAL, w/visualization by monoclonal

Ab, methenamine si lver sta i n , or PCR. • PO regi mens: Rx i n mild cases (Po 2 , > 70; A-a gradient, 48 hr after admission ( 1 9 mg/d l, R: RR >30 m i n , BP 1 , hospital ize (higher score , h igher mortal ity) .

Imaging (chest x-ray: PA •

•

+

lateral)

Segmental lobe infiltrate : pneumococcal pneumonia Diffuse infi ltrates: Legionella pneumophi/a, Mycoplasma pneumoniae, viral pneumonias, Pneumocystis jiroveci, m i l iary TB, aspiration, aspergi llosis

Treatment •

•

• •

•

Macrolides (azith romycin or clarith romycin) or levofloxacin for empiric outpt Rx; cefotaxime or a �-lactam/�-lactamase i n h i bitor can be added in pts w/more severe presentation who insist on outpt Rx. Duration of Rx: 7 to 1 4 days . I n pts admitted to general medical ward : second- or third-generation cephalosporin (ceftriaxone, ceftizoxime, cefotaxime, or cefuroxime) + a macrolide (azith romyci n or clarithromycin) or doxycyc l i n e . An antipseudomonal q u i nolone (levofloxacin or moxifloxacin) may be substituted i n place of the macrolide or doxycycline. Empiric Rx i n ICU pts: IV �-lactam (ceftriaxone, cefotaxi me, ampici l l i n-sul bactam) + an IV qui nolone (levofloxacin, moxifloxacin) or IV azithromycin In hospitalized pts at risk for P . aeruginosa infectio n : antipseudomonal �-lactam (cefepime or pi perac i l l i n-tazobactam) + an AG + an antipseudomonal qui nolone or macrolide In pts w/suspected M RSA: vancomycin or l i nezolid

Clinical Pearls •

•

Causes of slowly resolving or nonresolving pneumonia: difficult-to-treat infections: viral pneumonia, Legionella, pneu mococc i , or staphylococci w/ i m paired host response; TB, fungi , neoplasia ( l u ng, lymphoma, mets) , C H F , PE, i m m unologic/idiopath i c : Wegener's gra n u lomatosis, pul monary eosinoph i l i c synd romes, SLE, Drug toxicity (e.g. , am iodarone)

ASPIRATION PNEUMONIA • •

:!:

LUNG ABSCESS

Etiology: 3 5% anaerobes, 26% Gram (+) cocci , 25% Klebsiella pneumoniae Rx: pi perac i l l i n-tazobactam 3 . 3 7 5 g IV q6h or 4-hr i nfusion of 3 . 3 7 5 g q8h or

(ceftriaxone 1 g IV q24h + metronidazole 500 mg IV q6h)

MYCOPLASMA PNEUMON IAE Diagnosis H&.P •

Nonexudative pharyngitis (common) , rhonchi or rales, w/o evidence of consol idation (common) in lower lung zones; associated w/bul lous myringitis

Imaging •

CXR: pred ilection for lower lobe i nvolvement (upper lobes 1 00 kg, 1 . 5 g IV q 1 2 h Breast Implant Infection •

•

Acute : vancomycin 1 g IV q 1 2h ; if > 1 00 kg, 1 . 5 g q 1 2 h Chron ic: Await culture results .

D LUNG ABSCESS Etiology

•

•

Aspiration is the most common factor. 90% of abscesses are caused by anaerobic microorganisms (Bacteroides fragilis, Fusobacterium, Peptostreptococcus) .

• •

In most cases , anaerobic infection is mixed w/aerobic or facu ltative anaerobic organisms (S. aureus, Escherichia coli, K. pneumoniae, P. aeruginosa) . l m m unocompromised hosts may become infected w/Aspergillus, Mycobacteria, Nocardia, and Rhodococcus equi.

Diagnosis H&P •

•

Fever, cough, sputum production (purulent w/fou l odor) , hemoptysis Dull ness to percussion , whispered pectoriloquy and bronchophony

Labs • •

Blood tests nonspecific/rarely helpfu l : CBC w/leukocytosis, blood cultures, sputum Gram stai n and culture Fiberoptic bronchoscopy with use of bronchial brushi ngs or BAL fl uid hel pfu l to obtain dx bacteriologic cultures

Imaging •

•

CXR: cavitary lesion w/an air-fluid level Chest CT: local ize and size lesion, assist in differentiating from other processes

Treatment • • •

PCN 1 to 2 m i l l ion U IV q4h unti l i m p rovement, fol l owed by PCN V K 500 mg qid for at least 3 wk Metron idazole given w/PCN at doses of 7 . 5 mg/kg IV q6h fol l owed by PO 500 mg bid to qid Cli ndamycin (if concerned about PCN resistance) 600 mg IV q8h, then by 300 mg PO q6h

Clinical Pearls •

234

•

•

Risk factors : alcoholism, seizure disorder, CVA w/dysphagia, poor oral hygiene, bronchiectasis, obstructive l u ng lesions, esophageal disorders, drug abuse Cure rate >95% w/appropriate abx Necrotizing pneumonia is si milar to l u ng abscess but differs i n size (90% sensitivity) Surgical diagnostic options: CT-guided drainage, laparoscopy w/drainage and irrigation, transvagi nal col potomy (midline abscess) , laparotomy

Treatment •

•

•

Decision on whether pt requires immediate surgery (uncertai n dx or suspicion of rupture) or management w/IV abx, w/surgery reserved for pts w/inadequate c l i nical response Cli ndamycin 900 mg IV q8h + gentamicin 5 to 7 mg/kg q24h or 1 . 5 mg/kg q8h Alternatives: ampici l l i n-sul bactam 3 g IV q6h, or cefoxitin 2 g IV q6h, + doxycycline 1 00 mg IV q 1 2 h

0 PERIRECTAL ABSCESS Etiology

•

Polym icrobial aerobic (S. aureus, Streptococcus species, E. coli) and anaerobic bacteria (B. tragi/is , Peptostreptococcus species, Prevotella species, Fusobacterium species)

Diagnosis H&.P • •

Local ized peri rectal or anal pa i n , often worsened w/movement or stra i n i ng; peri rectal erythema or mass by i nspection or pal pation Many pts have predisposing conditions ( D M , mal ignant neoplasm/leukemia, immune deficiency, steroid Rx, recent surgery) .

Labs •

CBC w/diff; local aerobic and anaerobic cultures; blood cultures if toxic, febri le, or immunocom promised

Imaging •

•

Sigmoidoscopy i n selected cases Imaging (pelvic CT) usually not indicated un less extensive disease , abscess, or immunocom prom ised pt

Treatment •

•

•

•

I&D; debridement if necrotic tissue, r/o need for fistulectomy Local wound care: packing, Sitz baths Outpt abx-PO • Amoxici l l i n/clavulanic acid 875 to 1 000 mg bid • Ciprofloxacin 750 mg PO q 1 2 h + metron idazole 500 to 750 mg PO q8h or • Cli ndamycin 1 50 to 300 mg PO q8h l n pt abx-IV • Ampicill in-sulbacta m (U nasyn) 1 . 5 to 3 g IV q6h • Cefotetan 1 to 2 g IV q8h • Pi perac i l l i n-tazobactam 3 . 37 5 g IV q6-8h • l mi penem 500 to 1 000 mg IV q8h

0 PERITONSILLAR ABSCESS

Infection located between the capsule of the palatine tonsil and the superior constrictor muscle of the pharynx

Etiology •

•

•

•

Peritonsillar abscess is a compl ication of tonsi l l itis. Group A �-hemolytic streptococcus is the most common bacterial cause, accounting for 1 5% to 30% of cases in c h i ldren and 5% to 1 0% of cases in adults. Less common aerobic ca uses are S. aureus , H. influenzae , Neisseria species. The most common anaerobic organism is Fusobacterium.

Diagnosis H&.P •

236

•

•

•

Sore throat, which may be severe ; dysphagia and odynophagia; otalgia; fou l-smell i ng breath Facial swe l l i ng, droo l i ng, headache, fever, trismus Hoarseness, muffled voice (also called " hot potato voice") Tender submandibular and anterior cervical lymph nodes, tonsi llar hypertrophy, contralateral deflection of the uvula, stridor

Labs •

•

Rapid strep antigen-detecti ng testing and throat swab C&S Aspiration of the abscess for C&S

Imaging •

CT soft tissue of neck

Treatment •

Empiric abx Rx

• PO: amoxicillin-clavu lanic acid 875 mg bid, PCN VK 500 mg qid + metron idazole

500 mg qid, or cli ndamycin 600 mg bid • IV: ampici l l i n-sul bactam 3 g q6h or cli ndamycin 900 mg q8h • •

•

Steroids may be hel pful i n reducing sx and speeding recovery. Tonsillectomy: 3 to 6 mo after dx Although rare , in adu lts and children w/peritonsillar abscess and h/o recurrent pharyngitis or peritonsillar abscess, the specialist may proceed w/tonsil lectomy (a qui nsy or " hot" tonsi l lectomy) d i rectly after prescribing the pt IV abx.

Clinical Pearl •

Complications: airway obstruction , l ung abscess or aspi ration pneumonia, G N , rheu matic fever, erosion i nto carotid sheath, a n d extension o f i nfection i nto tissues of the deep neck or posterior mediastin u m .

D RETROPHARVNC EAL ABSCESS

Soft tissue infection of the retropharyngeal space (middle [anteriorly] and deep [posteriorly] layers of the deep cervical fascia) Etiology Streptococcus pyogenes (group A streptococcus [GAS ] ) . S. aureus, and respi ratory anaerobes (Fusobacterium, Prevotella, and Veil/one/fa species) , Haemophilus

•

• •

(occasional) I n young chi ldren , i nfection via lym phatic spread from a pharyngeal/sinus septic focus In adults, i nfection via local penetrating trauma (e.g. , ch icken bones or after instrumentation) or odontogenic sepsis and peritonsillar abscess (rare)

Diagnosis H&P • • •

• •

Insidious onset fever, irritabil ity, drooli ng, a m uffled voice (dysphonia) . or possibly nuchal rigidity Possible i ntense dysphagia/drool ing/odynophagia, or element of respi ratory distress from edema and i nflammation of the a i rway (stridor and/or tachypnea) Unwi l l ingness to move the neck because of d iscomfort (promi nent presenting feature; especially if febrile/i rritable child) causing pt to present holding neck stiffly or w/torticollis Trismus is unusua l . Possible midline/unilateral swelling o f posterior pharyngeal wall; mass may b e fluctuant to the examining finger (care must be taken to avoid abscess rupture into airway)

Imaging •

•

CT of soft tissues of the neck MRI of neck w/gadol i n i u m (l sensitivity than CT)

Treatment • •

PCN (2-4 million U IV q4h) + metronidazole ( 1 -g IV loading dose then 500 mg IV q6h) or ampicillin-sulbactam (50 mg/kg/dose IV q6h) or clindamycin (600-900 mg IV q8h) Surgical : drai nage indicated if large hypodense area or pt unresponsive to IV Rx alone

Clinical Pearl •

Complications are numerous and could be fatal (airway obstruction, septicem ia, internal j ugular vein thrombosis Lemierre s syndrome, carotid artery rupture, acute necrotizing med iastin itis) . Aspiration w/resultant pneumonia may complicate retropharyngeal abscess if rupture of the abscess occurs and empties into the airway. -

'

E . SKIN/SOFT TISSUE/BONE/JOINT

INFECTIONS 0 CELLULITIS Superficial i nflammatory condition of the skin characterized by erythema, warmth , and tenderness of the area i nvolved

237

Etiology •

•

Group A �-hemolytic streptococci (may fol low streptococcal U R I ) Staphylococcal cel l u l itis

•

•

H. influenzae Vibrio vulnificus: l incidence pts w/l iver disease (75%) and in i m m u nocompromised

hosts (corticosteroid use, D M , leukem ia, renal fai l u re)

Erysipelothrix rhusiopathiae: handlers of poultry, fish, or meat • Aeromonas hydrophila: contami nated open wound i n fresh water • Fu ngi (Cryptococcus neoformans}, Gram (-) rods (Serratia, Enterobacter, Proteus, Pseudomonas): i m m unocompromised granulopenic pts Diagnosis H&P •

• •

• •

Erysipelas: su perficial spreading, warm , erythematous lesion distinguished by indurated and i margi n ; lymphatic i nvolvement + vesicle formation common Staphylococcal cel l u l itis: area erythematous, hot/swollen; differentiated from erysipelas by nonelevated poorly demarcated margin ; local tenderness/regional adenopathy common (85% cases occur on legs and feet) H. influenzae cell u l itis (children, face; adults, neck/upper chest) : area blue red/purple red Vibrio vulnificus (critically i l l pt in septic shock): larger hemorrhagic bullae, cel l u l itis, lym phadenitis, myositis

Labs •

In severe cases, CBC w/diff, Gram stai n/culture (aerobic and anaerobic) . blood cultures, ASO titer (in suspected streptococcal disease)

Treatment Extremities, Nondiabetic (Leg Elevation Helpful) •

• •

• •

l n pt: PCN G 1 to 2 m i l l ion U IV q6h or cefazol i n 1 g IV q8h * If PCN allergy: vancomycin 1 5 mg/kg IV q 1 2 h If afebrile: PCN V K 500 mg PO qid ac and hs x 1 0 days Outpt: PCN V K 500 mg PO qid ac and hs x 1 0 days * If PCN allergy: azithromycin 500 mg PO x 1 , then 250 mg PO daily x 4 days

Facial, Erysipelas •

•

Pri mary: vancomycin 1 g IV q 1 2 h ; if > 1 00 kg, 1 . 5g IV q 1 2 h Alternate : daptomyci n 4 mg/kg IV q24h or l i nezolid 600 mg IV q 1 2 h

Orbital Cellulitis •

•

•

•

•

•

Cellulitis

PO : dicloxac i l l i n 250 to 500 mg qid IV: nafc i l l i n 1 to 2 g q4-6h Cephalosporins (cephalothi n , cephalexi n , cephradi ne) also provide adequate antistaphylococcal coverage except for M RSA. Use vancomycin 1 . 0 to 2 . 0 g IV qd or l i nezol id 0 . 6 g IV q 1 2h in pts allergic to PCN or cephalosporins and in pts w/M RSA. Daptomycin (Cubici n ) , 4 mg/kg IV given over 30 m i n q24h, is also effective . Other agents that may be effective agai nst some strains of M RSA include quinupristi n-dalfopristi n (Synercid) and TMP-SMZ.

H aemophilus influenzae • •

anaerobes, GAS)

d ivided doses to achieve trough 1 5 to 20 �ml) + ceftriaxone 2 g IV q24h + metronidazole 1 g IV q 1 2 h ' tf PCN/cephalosporin allergy : vancomycin + levofloxacin 7 50 mg IV once daily + metronidazole IV

Staphylococcus •

(S. pneumoniae, H. influenzae, S. aureus,

Dx: i mage orbit (CT or M R I ) ; l risk cavernous sinus thrombosis Rx: nafc i l l i n 2 g IV (or if M RSA -+ vancomycin 30 to 50 mg/kg/day i n two to three

Cellulitis

PO : cefixime or cefuroxime IV: cefuroxime or ceftriaxone

Vibrio vulnificus •

•

Doxycycline 1 00 mg IV bid + ceftazidime 2 g IV q8h or IV ciprofloxacin 400 mg bid. Mild cases can be treated w/PO abx (doxycycline 1 00 mg bid + ciprofloxacin 750 mg bid). IV support and adm ission i nto ICU (mortal ity rate >50% in septic shock)

Erysipelothrix •

PCN

Aeromonas hydrophila

238

•

•

•

Am inoglycosides Chloramphen icol Complicated skin and skin structure i nfections in hospitalized pts can be treated w/daptomyci n (Cubicin) 4 mg/kg IV q24h.

Clinical Pearls • •

Cel l u l itis occurs most frequently in pts with D M , i m m u nocom promised hosts, and pts w/venous and lymphatic comprom ise . Frequently found near skin breaks (trauma, surgical wounds, ulcerations, ti nea infections)

10 METHICILLIN-RESISTANT STAPHYLOCOCCUS A UREUS Diagnosis H&P • •

CA-M RSA: can man ifest with skin i nfection; red bump, pustule, or boi l ; erythema, swe l l i ng; edema, often fl uctuant and very pai nful HA-M RSA: bacteremia; infection associated with IV device • Catheters (pneumonia), skin (ce l l u l itis) . bone (osteomyel itis) , endocarditis, abscesses, pneumonia (nosocomial)

W/up • • •

Culture of wound, abscess, blood , sputu m ; r/o colon ization; cu lture of nares or axi l lae Rad iographs or CT scan of suspected organ Echocard iogra m if endocarditis suspected

Treatment • • •

CA-M RSA: PO TM P-SMX-DS, doxycycline, minocycl ine, cli ndamycin (linezol i d expensive) HA-M RSA: IV vancomycin ( 1 5-20 mg/kg IV q8- 1 2 h ) , l i nezolid (600 mg) , daptomyc i n , telavancin Abscess surgically drai ned • Telavancin 1 0 mg/kg IV per day is bactericidal aga i nst M RSA. • Ceftaroline (fifth-generation cephalospori n) is also effective against M RSA. • Pts with M RSA colon ization may have re-exposure or may be unable to eradicate colon ized state . Eradication may be attempted via PO agents (rifampin, tetracycline, and minocycli ne) or mupirocin oi ntment to nares/i nfected skin sites.

D TOXIC SHOCK SYNDROME (TSS)

Acute febrile i l ln ess resulting i n m u ltiple orga n system dysfunction caused most commonly by a bacterial exotoxin Etiology • •

•

•

Menstrually associated TSS : 45% of cases associated w/tampons, diaphragm , or vagi nal sponge use Non-menstruati ng-associated TSS : 55% of cases associated w/puerperal sepsis, post-cesarean section endometritis, mastitis, wound or skin infection, insect bite , P I D , and postoperative fever Causative agent: S. aureus i nfection of a susceptible individual ( 1 0% of population lacking sufficient levels of antitoxin Abs) that l i berates the disease mediator TSST1 (exotoxin) Other causative agents: coagulase(-) streptococci producing enterotoxins B or C , and exotoxi n A producing group A �-hemolytic streptococci

Diagnosis H&P •

• • •

•

•

•

•

Fever (>38.9° C) , myalgia , headache, photophobia , rigors/arth ralgia, conjunctivitis Diffuse macular eryth rodermatous rash that desq uamates 1 to 2 wk after disease onset in survivors Orthostatic to severe hypotension and ARF Gl sx: vomiti ng, diarrhea , abd tenderness Respi ratory sx: dysphagia, pharyngeal hyperemia, strawberry tongue G U sx: vagi nal d/c, vagi nal hyperem ia, adnexal tenderness End-organ fai l u re (ARF , hepatic fai l u re) CV sx: DIC, pulmonary edema, ARDS, endomyocarditis, heart block

Labs • •

•

•

•

•

•

Pan culture (cervix/vagi na, th roat, nasal passages, urine, blood , CSF, wound) for Staphylococcus, Streptococcus, or other pathogenic organisms

Electrolytes to detect hypokalemia, hyponatremia CBC w/diff, PT, PIT Total Prote i n , AST, ALT. hypocalcemia, BU N/Cr. hypophosphatemia, LD H , CPK U/A: WBC (>5/h pf) , proteinemia, microhematuria ABGs (assess respi ratory function and acid-base status) Serology (RMSF, Lyme disease, rubeola, and leptospirosis)

239

Imaging • •

CXR U/S , CT scan , M R I : if abd/pelvic abscess suspected

Treatment •

•

• •

• •

• •

• •

•

•

•

•

•

•

Aggressive fl uid resuscitation (maintenance of circulating vol u m e , CO, BP) Search for localized i nfection/n idus: I&D, debridement, removal of tampon or vagi nal sponge Consider central hemodynamic mon itoring: Swan-Ganz catheter and A-l i n e for surve i l lance of hemodynamic status and response to Rx Foley catheter to monitor hourly urine output Possible MAST trousers as temporary measure Staphylococcal : nafc i l l i n or oxac i l l i n 2 g IV q4h or (if M RSA, vancomycin 1 g IV q 1 2 h + cli ndamycin 600 to 900 mg IV q8h + IVIG 1 g/kg day 1 , then 0 . 5 g/kg days 2 and 3) Streptococcal: PCN G 24 m i l l ion U/day IV i n divided doses + c l indamycin 900 mg IV q8h or ceftriaxone 2 g IV q24h + cli ndamycin 900 mg IV q8h Doxycycline added if RMSF is being considered * IVIG associated with l i n sepsis-related organ fa ilure : dose = 1 g/kg day 1 , then 0 . 5 g/kg days 2 and 3 Acute venti lator management if severe respi ratory compromise Renal dialysis for severe renal i mpairment Surgical i ntervention as indicated ( i . e . , ruptured tuba-ovarian abscess, wound abscess, mastitis) Isotonic crystalloid (NS solution) for volume replacement fol lowing "7-3" rule Electrolyte replacement (K+, Ca+) PRBC, coagulation factor replacement, or FFP to treat anemia or D&C Vasopressor Rx for hypote n s i o n refracto ry to fl u i d vo l u m e re p l a c e m e nt ( i . e . , dopamine 2-5 mg/kg/m in)

0 DIABETIC FOOT IN FECTIONS Etiology

•

•

Staphylococci/streptococci Most often s/p trauma via neuropathy, vascular insufficiency, and immunodeficiency

Diagnosis Clinical Findings

•

•

•

Mild (2 e m : gangrene, deep tissue abscess, spread to lymph/muscle/joi nt/ tendon) Severe (limb-th reatening, fever, tachycardia, hypotension, kidney i njury, �MS, leukocytosis)

W!up •

•

Assessment for possible a rterial i nsufficiency, bone i nvolvement Wound care with cleansing, debridement, and off-load ing of pressu re

Treatment • • •

•

All diabetic pts should have at least annual foot exami nation assessing l sensation, u l cers, call uses, foot deformities, pai n , abnl pain sensation, and peri phera l pu lses. Ulcers that are clin ically uni nfected should not be Rx with abx. Abx should cover G ram (+) staph/strep . Severe infection (limb-th reaten i ng) requires surgical eval uation and i n itial broadspectrum abx.

1J NECROTIZING FASCIITIS

Deep-seated i nfection of SC tissue resulting in progressive destruction of fascia and fat Etiology

•

•

•

240

Prior su rgery Trauma Causative organisms: streptococci , clostridia, m ixed flora (polym icrobi c : aerobic + anaerobic [Meleney's synergistic gangrene if S. aureus + anaerobic strep]), CA­ M RSA

Diagnosis H&.P • •

Diffuse swell i ng of an arm or leg, followed by the appearance of bullae fi l led w/clear fl uid (can appear maroon or violaceous) Systemic sx may include shock and organ fai l ure.

Labs •

Incision and probing of site , Gram sta i n , C&S

Imaging •

CT or M R I of affected extrem ity

Treatment •

• • •

Surgical debridement, Gram stai n/cu lture , in addition to abx If strep or clostridia: PCN G 24 m i l l ion U/day div q4-6h IV + clindamycin 900 mg IV q8h If polym icrobial: i m i penem or meropenem Add vancomycin or daptomycin if M RSA suspected

0 MUSCLE ("CAS GANGRENE") •

•

•

Primary Rx: clindamycin 9 0 0 m g I V q 8 h + P C N G 24 m i l l ion U/day d ivided q4-6h IV Alternative Rx: ceftriaxone 2 g IV q 1 2h or erythromycin 1 g q6h IV Surgical debridement essenti a l ; hyperbaric 0 2 possi ble adjunctive Rx (efficacy variable)

D BITES

Animal Bites •

Dog bites < l i kely to become infected than cat bites

Management •

•

• •

•

Adequate wound irrigation/debridement + abx if infected wound Need for tetanus and rabies prophylaxis determi ned Abx prophylaxis needed : i m m unocompromised, wound near joi nt/bone, crush inj u ry, edematous wound Rx cat bite (Pasteurella multocida}: amoxic i l l i n-clavulanate (87 5/ 1 25 mg PO bid or 500/ 1 2 5 mg PO tid) or doxycycl i ne 1 00 mg PO bid Rx dog bite (Pasteurella canis}: amoxicilli n-clavulanate (87 5/ 1 2 5 mg PO bid or 500/ 1 2 5 mg PO tid) or cli ndamycin 300 mg PO qid + fl uoroqui nolone

Human Bites • • • •

•

Early: amoxici l l i n-clavulanate 875/ 1 2 5 mg PO bid x 5 days; late: ampici l l i nsulbactam 1 . 5 g IV q6h or cefoxitin 2 g IV q8h * If PCN allergy: c l indamycin + (ciprofloxacin or TM P-SMX) Debridement with wound cleaning/i rrigation essential Prophylactic therapy for persons bitten by others with H IV and/or hepatitis B Clenched-fist i njuries require radiographic eval uation, possibly hospitalizatio n .

0 OSTEOMYELITIS

I nfection of bone and bone marrow

Etiology • S. aureus : most common • Gram (-) baci l l i : Salmonella, E. coli, Pseudomonas, Klebsiella • Salmonella: sickle cell disease • Pseudomonas: IV drug addicts; puncture wounds i n sneakers • Coagu lase(-) staphylococci or Propionibacterium: foreign body •

•

•

Anaerobes: infected decubitus ulcers in sacrum Bartonella henselae: H IV i nfection P. multocida or Eikenella corrodens : human or animal bites

Diagnosis • • •

•

Tenderness over the bone and l i m itations of movement of the involved extremity Defi n itive dx via isolation of i nfective organism from bone or joint fl uid obta i ned either by surgery or m u ltiple percutaneous needle bx MRI : most accurate i maging study Doppler studies: in pts w/PVD to determ ine vascular adequacy

Treatment •

•

Hematogenous osteomyel itis empiric Rx • M RSA possible: vancomycin 1 g IV q 1 2 h ; if > 1 00 kg, 1 . 5 g IV q 1 2 h • M RSA u n l i kely: nafc i l l i n or oxaci l l i n 2 g IV q4h • Allergy/toxicity: TM P-SMX 8 to 1 0 mg/kg per day divided IV q8h or l i nezolid

600 mg IV/PO q 1 2 h Contiguous osteomyel itis without vascular insufficiency empiric Rx • Primary: ciprofloxacin 7 50 mg PO bid or levofloxacin 750 mg PO q24h • Alternative : ceftazidime 2 g IV q8h or cefepime 2 g IV q 1 2 h

241

•

•

Contiguous osteomyelitis with vascular insufficiency • No empiric Rx un less acutely i l l ; debride ulcer and submit bone for histology and culture, selecti ng abx based on resu lts. Rx for 6 wk. Chronic osteomyelitis • Surgical debridement i m portant, immobil ization of affected bone (plaster, traction) if bone is unstable.

lJ SEPTIC ARTHRITIS

Etiology S. aureus , P-hemolytic strep, and Gram (-) bac i l l i

•

•

Gonococcus

Diagnosis • • •

Acute onset of a swollen pai nful joint, l range of motion, erythema, l warmth around the joint Joint aspiratio n , G ram stain and C&S of synovial fl uid (synovial fl uid leukocyte count is usually >50,000 cells/m L3 w/a diff count of 80% or more PMNs) Joint x-ray, CT sca n , tech netium and gal l i u m scans

Treatment •

•

•

•

At risk for STD. G ram stain(-) : ceftriazone 1 g IV q24h At risk for STD, G ram stain(+) : vancomycin 1 g IV q 1 2h ; if > 1 00 kg, 1 . 5 g IV q 1 2 h No risk for STD: a l l empiric choices guided by Gram stai n • Vancomycin + thi rd-generation cephalosporin 1 0 t o 1 4 days • Vancomycin + (ciprofloxacin or levofloxacin) 1 0 to 1 4 days • Acute, polyarticular: ceftriaxone 1 g IV q24h • S/p i ntra-articular injection: no empiric Rx (arthroscopy for C&S, crystals, washout; Rx based on culture results x 1 4 days assuming no foreign body present) Infected prosthetic joint • Cultures pend ing: no empiric Rx, need C&S results; may l culture yield via sonication • S. pyogenes/vi ridans strep : debridement + prosthesis retention; PCN G or ceftriaxone IV x 4 wk • Methicillin-sensitive Staphylococcus epidermidis (MSSE)/MSSA: (nafcillin/oxacillin 2 g IV q4h + rifampin 300 mg IV/PO bid) or (vancomycin 1 g IV q 1 2h + rifampin 300 mg IV/PO bid) or (daptomycin 6 mg/kg IV q24h + rifampin 300 mg IV/PO bid) x 6 wk • Meth ic illi n-resistant Staphylococcus epidermidis (MRS E)/M RSA: (vancomycin 1 g IV q 1 2 h + rifampin 300 mg IV/PO) x 6 wk • P. aeruginosa: ceftazidime 2 g IV q8h + (ciprofloxacin 750 mg IV/PO bid or levofloxacin 7 50 mg IV/PO q24h)

[[!] SEPTIC BURSITIS

I nflammation with i nfection of a b u rsa (th i n-wa l l ed sac l i ned with synovial tissue facilitating movement of tendons/m uscles over bony promi nences) Etiology

•

• • •

Acute trauma or repetitive inj u ry Infection: from hematogenous seeding or spread from contiguous infection (septic bursitis) Crystal diseases (e.g. , gout, pseudogout) Systemic arthritis ( i . e . , rheumatoid arth ritis)

Diagnosis H&.P •

•

•

•

Swe l l i ng, when bursitis is superficial (olecranon , prepatellar) Local tenderness at site of bursa ; pain with joint movement and rest Peribursal erythema and warmth (septic bursitis) Referred pain

W/up •

Bursal fl uid aspiration: Send for Gram stai n and cultu re and sensitivity (C&S) cell count and diff; and crystal analysis.

Imaging • •

•

Plain radiography: Rio foreign body penetration and other potential/coexisting bone/joint problems. MRI (extent of soft tissue involvement) Musculoskeletal U/S can aid visual ization of bursae and guide aspi ration/i njectio n .

242 Treatment • Avoidance of d irect pressu re or irritation Uoint protection) with rest, ice, elevation, and physical Rx for acute phase

•

•

• •

Septic • If MSSA: nafc i l l i n or oxaci l l i n 2 g IV q4h or d icloxac i l l i n 500 mg PO qid • If M RSA: vancomycin 1 5 to 2 0 mg/kg IV q8- 1 2 h or l inezolid 600 mg PO bid • 7 days of a bx may be sufficient fo r i m m u nocom petent pt undergoing one­

stage b u rsecto my because i m m u nosuppression (not Rx d u ration) l recurrence risk. • Drainage + aspiration of purulent fl uid with a large-bore needle (if there is no rapid c l i n ical response, incision and drai nage are indicated) Nonseptic: aspiration of bursal fl uid or blood from acute trauma Chronic pain may warrant steroid i njection i nto bursa (40 mg triamci nolone m ixed with 1 -3 ml l idocaine, depending on size of bursa). N SAI Ds PRN

Clinical Pearls • •

• •

In pts with RA, acute bursitis should be considered septic bursitis u ntil proven otherwise . Scapulothoracic bursitis is underrecognized and undertreated. It results from friction between the superomedial angle of the scapula and adjacent second and third ribs. Crepitus, snapping, and tenderness are suggestive fi ndi ngs; it can also cause chest wal l pai n . Steri le bursae should not undergo I&D because a chron ic dra i n i ng sinus tract may develop. Pts with crystal-induced bursitis should be investigated for underlying metabolic/ hematologic disease (gout, hemochromatosis, hyperparathyroid ism-calcium pyrophosphate deposition disease) .

m SKIN INFESTATIONS a. Scabies (Sarcoptes scabiei) Diagnosis •

•

•

Via cli nical presentation + m ites, eggs, or mite feces I ntense pruritus (especially nocturnal) 1 to 4 wk after the primary infestation (in web spaces of the hands, wrists, buttocks, scrotu m , penis, breasts, axi l lae, and knees) from acquired sensitivity to the m ite or fecal pellets Skin exa m : bu rrows, tiny vesicles, excoriations, i nflam matory papules

Treatment • • •

•

Permeth ri n 5% cream massaged i nto the skin from head to soles of feet. Remove 8 to 1 4 hr later by wash ing. PO ivermectin single dose ( 1 50-200 mg/kg) Topical corticosteroid creams for secondary eczematous dermatitis AIDS and HTLV-infected (CD4 < 1 50 per m m 3 ) pts: permeth rin 5% cream daily x 7 days, then 2 x wk until cured

b. Bed bugs Etiology Cimex hemipterus/Cimex lectularius : nocturnal feeding via sal iva containing

•

nitrophorin (anticoagu lant i nterfering with factor Xa , i n h i biting Pit aggregation)

Diagnosis •

•

• • •

•

Fi rm , purpuric/erythematous macules, papules, u rticaria, or bul lae may be present. Bite may have a central hemorrhagic punctu m ; it is generally on areas of exposed ski n . Insect h a s poor attachment mechanism; thus person-person transmission i s u n l i kely. Victim may observe a l i n ear series of three bites ( " brea kfast, l u n c h , and dinner"). W/up begins with hx and physical for clin ical s x and environmental fi ndi ngs. Bites are histologically si milar to other insect bites (perivascular infi ltrate of lym phocytes, histiocytes , eosinoph ils, and mast cells with i n upper dermis) .

Treatment •

•

Topical glucocorticoids/systemic antih istam ines if severe pruritus • Triamcinolone cream 0 . 1 %. Apply thin fi lm to affected areas bid. • Chlorphen i ramine 4 mg PO hs (adu lts) , 2 mg PO hs (children) M u lti-insecticides (because of resistance) may be effective in erad ication; consult � oo�l . • Use permethrin spray for clothing and bedsheets or bednets . • Deltameth rin and chlorfenapyr are two common insecticides used .

�

c. •

Lice (Pediculosis) Head lice Rx: Permethrin 1 % lotion to sham pooed/dried hair 1 0 m i n . Repeat in

9 days.

•

Pubic lice Rx ( " crabs " ) : Permeth rin 1 % lotion to clean/dried hair 1 0 m i n . Repeat i n

•

Body lice Rx: No abx; l ice in cloth i ng, thus discard . If not possible, apply 1 %

9 days. malathion powder to cloth i ng.

F. FEVER OF UNKOWN ORIGIN (FUO) Table 8- 1 describes defi n itions and major features of the four subtypes of FUO.

G. SEXUALLY TRANSMITTED DISEASES

0 CHLAMYDIA TRACHOMA TIS I NFECTION •

This most common bacterial STI in U n ited States results in ureth ritis, epididymitis, cervicitis, and acute salpingitis, but often asx in women. I n men, sx include urethritis, m ucopurulent d/c , dysuria, ureth ral pruritus.

Diagnosis H&P •

Clin ical man ifestations may be similar to those of gonorrhea: m ucopurulent endocervical d/c w/edema, erythema, and easily ind uced endocervical bleeding caused by i nflammation of endocervical columnar epithelium. Less frequent man ifestations may include bartholinitis, urethral syndrome w/dysu ria and pyuria, peri hepatitis (Fitz-Hugh-Curtis syndrome).

Labs • •

•

Cell culture (si ngle culture sensitivity 80%-90%) . but it is labor i ntensive/takes 48-96 hr. It is not suited for large screening programs. Nonculture methods • DFA, EIA, DNA probes, PCR • Withe exception of PCR, the other tests are probably less specific than cell culture and may yield false(+) resu lts. Because this is an i ntracellular organism, purulent d/c is not an appropriate specimen. An adequate sample of infected cells m ust be obta i ned.

Treatment • •

•

•

Eval uation and Rx of sex partners N G U , u reth ritis, cervicitis, conjunctivitis (except for LGV) • Primary: azith romycin 1 g PO x 1 or doxycycl i n e 1 00 mg PO bid x 7 days • Alternatives: erythromycin base 500 mg PO qid x 7 days or levofloxacin 500 mg q24h x 7 days Pregna ncy: erythromycin base 500 mg PO qid x 7 days or amoxici l l i n 500 mg PO tid x7 days • Note: Doxycycl i n e and ofloxacin/levofloxacin are contraindicated in pregnancy. Recurrent/persistent urethritis: metron idazole 2 g PO x 1

Clinical Pearl •

Assume concom itant gonorrhea co-infectio n : PO ceftriaxone 1 2 5 mg I M si ngle dose + azithromycin 1 g PO si ngle dose wi l l treat both.

0 NEISSERIA GONORRHOEA£ I NFECTION

Th is second most commonly reported bacterial sexually transm itted i nfection mani­ fests as ureth ritis, cervicitis, or salpi ngitis. Infection may be asx ( 1 2%- 1 5% men, 50%80% women). differing between male and female pts i n course/severity. Diagnosis

•

•

•

•

Gram(-) i ntrace l l u lar diplococci diagnostic in male urethral smears, 60% to 7 0% false(+) in female cervical/urethral smears. Culture, n ucleic acid hybridization tests, and n ucleic acid ampl ification tests (NMTs >99% specificity) requ i re endocervical (female)/urethral (male) swab, or urine testing. Culture on Thayer-Marti n med i u m (sensitivity 38.0'C, >3 wk, >2 visits or 1 wk i n hospital

Observation, outpatient temperature chart, i nvestigations, avoidance of empiric d rug treatments Months Weeks

Health care-Associated FUO

lmmune-Defklent FUO

HIV-Related FUO

�38.0'C, >3 wk for outpatients, > 1 wk for inpatients, HIV infection confi rmed Community, clinic, or hospital H IV (primary i nfecti on). typical and atypical mycobacterial i nfection , CMV i nfection, lymphomas, toxoplasmosis, cryptococcosis, immune reconstitution i nflammatory syndrome (IRIS) D rugs, exposures, risk factors , travel , contacts, stage of HIV i nfection

�38.0'C, > 1 wk, not present or incubating on admission Acute care h ospital H ealth care-associated i nfections, postoperative complications, drug fever

�38 .0'C, > 1 wk, negative cu ltures after 48 hr Hospital or clinic Majority caused by infections, but cause documented in only 40%-60%

Operations and p rocedures, devices , an atom ic considerations, drug treatment

Stage of chemotherapy, drugs administered, underlying immunosuppressive disorder

Wounds, drains, devices, sinuses, u rine

Ski n folds, IV sites, l ungs, perianal area

M outh , sin uses, skin , lymph n odes, eyes, l ungs, p eria nal area

I m aging, bacterial cultu res

CXR . bacterial cultures

Depends on situation

Anti microbial treatment protocols

B lood and lymphocyte count; serologic tests; CXR; stool examination; biopsies of l ung, bon e marrow, and liver for cultu res and cytologic tests; brain imaging Antiviral and antimicrobial protocols, vaccines, revision of treatment regi mens, good n utrition

Weeks Days

Days Hours

Weeks to month s D ays to weeks

Adapted from Mandel l GL, Ben nett, JE, Dolin R (eds): Mandell, D ouglas, a nd Bennett's Principles and Practice of I nfectious Di seases, 7th ed. Philadel phia, Churchi ll Livingstone , 20 1 0, p 780. From Kliegman R M , Stanton B . St. Geme J, et al (eds) : Nelson Textb ook of Pediatrics, 1 9th ed. Phi ladelphia, Saunders , 2 0 1 1 .

I�

•

•

Female pts: i n itial ureth ritis or cervicitis may occur days after exposure, frequently m i l d ; uterine i nvasion (20%) after menstrual period with sx of endometritis, sal p i ngitis, or pelvic peritonitis. Pts may have purulent d/c or i nflamed Skene's or Barth o l i n ' s glands. Acute gonococcal PID: fever, abd and adnexal tenderness, i n absence of purulent d/c. Disseminated gonococcal infection may manifest with various skin lesions.

Treatment •

•

•

Uncompl icated infections of the cervix, ureth ra , and rectum • Ceftriaxone 250 mg IM + azithromycin 1 g PO or doxycycline 1 00 mg PO bid for

7 days Alternative regi mens • Cefixime 400 mg PO + azithromycin 1 g PO or doxycycline 1 00 mg PO bid for 7 days + test of cure at 1 wk • Cephalospori n allergy: azithromycin 2 g PO + test of cure at 1 wk Uncom plicated gonococcal infections of the pharynx • Ceftriaxone 250 mg IM + azithromycin 1 g PO or doxycycline 1 00 mg PO bid for 7 days • Pregnant pts req u i re test of cure (recu lture 4-7 days s/p Rx) . • All sexual partners should be identified, examined, tested, and receive presum ptive Rx. • This is a reportable disease .

0 PELVIC I NFLAMMATORY DISEASE (PID) •

Spectru m of inflammatory disorders of the upper gen ital tract Endometritis, salpi ngitis, tubo-ovarian abscess, or pelvic periton itis Resulting from an ascending lower genital tract i nfection Not related to obstetric or surgical i ntervention Most common cause of female i nfertil ity and ectopic pregnancy

• • • •

Risk Factors •

Adolescent sexually active females 38 . 3°C ( 1 0 1 °F) , abnl cervical or vagi nal d/c , i ESRICRP, cervical infection (N. gonorrhoeae/C. trachomatis}, leukocytosis with i WBC on saline m icroscopy of vagi nal fl uid G ram sta in endocervical exudate : >30 PMN cells/h pf (chlamydia!/ gonococcal) Endocervical cultures for N. gonorrhoeae and C. trachomatis Fallopian tube aspi rate or peritoneal exudate culture if laparoscopy performed �-hCG to rio ectopic pregnancy Defi n itive criteria: laparoscopic abnlities, histopathologic evidence of endometritis on biopsy (warranted i n women undergoi ng laparoscopy without visual evidence of salpi ngitis) , transvagi nal U/S (thickened fl uid-fi l led tubes with/without free pelvic fl uid/tuba-ovarian complex)

Treatment •

•

•

246

•

Empiric Rx: sexually active young women experiencing pelvic/lower abd pai n without other cause a n d with � 1 o f t h e fol lowing present on pelvic examination: uterine tenderness, adnexal tenderness, cervical motion tenderness Outpt Rx if: temp 4. 5 , malodorous d/c) • Rx: [metronidazole ( 0 . 5 g PO bid x 7 days) or (i ntravaginal gel 1 x/day x 5 days)) or tinidazole 2 g PO once daily x 3 days

D GENITAL ULCERS Differential Diagnosis

•

•

•

•

• •

• •

Herpes genitalis Syphilis Condyloma acumi natum Chancroid LGV Granuloma inguinale Neoplastic lesion Trauma

a. Syphilis • •

•

Systemic infectious disease caused by Treponema pallidum " Latent syphi l i s " (seroreactivity w/o other evidence of disease) "Tertiary syphilis" (gummatous and CV syph i l is)

Diagnosis H&.P •

•

•

Primary i nfection: ulcer or chancre at site of i nfection Secondary infectio n : rash, mucocutaneous lesions, and adenopathy Tertiary i nfectio n : cardiac, neurologic, ophthalmic, aud itory, or gum matous lesions

Labs •

•

Darkfield exami nations and DFA tests of lesion exudate or tissue Presum ptive dx is possible w/the use of two types of serologic tests for syph i l i s : ( 1 ) nontreponemal (e.g. , V D R L and rapid plasma reagi n) and (2) treponema! (e.g. , FTA-ABS and microhemaggl utination assay for Ab to T. pallidum) . The use of one type of test alone is not sufficient for dx.

247

TABLE 8-2 • Diagnostic Features and Management of Vaginal Infections

Etiology Typical symptoms Discharge Amount Color Consistency Vulvar/vagi nal inflammation p H of vaginal fl uid Amine ("fishy") odor with 1 0% KOH Microscopy

Yeast Vaginitis

Trichomoniasis

Candida a/bicans

and other yeasts

Trichomonas vagina/is

None

Vulvar itching, i rritation, i discharge

Malodorous frothy discharge, vulvar itching

Malodorous, slightly i discharge

Variable; usually scant Clear or white Nonhomogeneous, floccular

Scant to moderate White Clumped; adherent plaques

Profuse

Moderate

Yel low green Homogeneous

No

Yes

Yes

Usually white or gray Homogeneous, low viscosity; smoothly coats vaginal walls No

Usually 4.5

None

None

May be present

Present

Normal epithelial cells;

Leukocytes, epithelial cells, yeast, mycelia, or pseudomycelia in 40o/o-80% of cases

Leukocytes; motile trichomonads seen in 50o/o-70% of sym ptomatic patients, less often if asymptomatic

Oral fl uconazole; intravaginal azoles None

Metron idazole or tinidazole

Clue cells, few leukocytes; Lactobaci/Ius outnumbered by profuse mixed flora (nearly always including G. vagina/is plus anaerobes) Oral/intravaginal metronidazole or cli ndamycin None

No Infection

Lactobacillus

predominates

Usual treatment (see Formulary)

None

Management of sex partners

None

Treatment recommended

Bacterial Vaginosis Gardnerel/a vagina/is,

anaerobic bacteria, mycoplasma

From Tschudy MM, Arcara KM : The Harriet Lane Handbook, 1 9th ed. Philadelphia, Mosby, 20 1 2 .

Treatment • Early (pri mary, secondary, latent < 1 yr) : PCN G benzath ine 2 . 4 m i l lion U IM

azithromycin 2 g PO

• •

•

•

• •

x

1

x

1 or

More than 1 -yr duration (latent, CV, gumma) : PCN G benzath ine 2 . 4 m i l lion U I M q w k x 3 w k o r doxycycline 1 00 m g P O bid x 4 wk Neurosyphilis: aqueous crysta l l i n e PCN G 1 8 to 24 million U/day, admin istered as 3 to 4 m i l l ion U IV q4h x 1 0 to 1 4 days, or procaine PCN 2 . 4 m i l l ion U 1 M/day + probenecid 500 mg PO qid both for 1 0 to 1 4 days Congenital syphilis: aqueous crystal l i n e PCN G 50,000 U/kg/dose IV q 1 2 h x fi rst 7 days of l ife then q8h x 1 0 days, or procaine PCN G 50, 000 U/kg/dose 1 M/day x 1 0 days PCN-allergic pts w/primary or secondary syphilis: doxycycline 1 00 mg PO bid x 1 4 days, or tetracycl i n e 500 mg PO qid x 1 4 days, or ceftriaxone 1 g I M or IV x 8 to 1 0 days Latent syphilis in PCN-allergic pts: doxycycl i n e 1 00 mg PO bid or tetracycl i n e 500 mg qid for 28 days Tetracycl i nes are contraindicated in pregnancy. If the pt is pregnant and PCN allergic , she must be desensitized .

b. Herpes Simplex Virus (HSV) I nfection

After the primary infection, the virus enters the nerve endi ngs in the ski n directly below the lesions and ascends to the dorsal root gangli a , where it remains in a latent stage unti l it is reactivated . Diagnosis H&P •

248

Pri mary i nfection

• Sx occur 3 to 7 days after contact. • Constitutional sx incl ude low-grade fever, headache and myalgias, regional

lymphadenopathy, and local ized pai n .

• Pai n , burni ng, itching, a n d ti ngl ing last several hours.

• G rouped vesicles usually w/surrounding erythema appear and generally ulcerate

or crust withi n 48 hr.

• The vesicles are uniform i n size (differentiating it from herpes zoster vesicles,

which vary i n size) . • During the acute eruption, the pt is u ncomfortable; urinary retention may occur

i n severe cases.

• Lesions generally last 2 to 6 wk and heal w/o scarri ng. •

Recurrent i nfection • It is generally caused by alteration i n the imm une system , fatigue, stress,

menses, or local skin trauma.

• The prodromal sx (fatigue, burning and tingling of the affected area) last 1 2 to 24 hr. • A cluster of lesions generally evolves with in 24 hr from a macule to a papule and

then vesicles su rrou nded by erythema; the vesicles coalesce and subseq uently rupture with i n 4 days, reveal i ng erosions covered by crusts. • The crusts are generally shed with i n 7 to 1 0 days, reveal i ng a pink surface. • The most frequent location of the lesions is on the pen ile shaft or glans penis and the labia (HSV-2 ) . Labs •

•

•

•

DFA slide tests wi l l provide a rapid dx. Vi ra l culture (defi n itive dx) ; results i n 1 to 2 days. Lesions/cervical samples should be sampled during the vesicular/early ulcerative stage . Pap smear will detect H SV-infected cells in cervical tissue from women w/o sx. Serologic tests for H SV: lgG and lgM serum Abs. Abs to H SV occur in 50% to 90% of adults.

Treatment Genital Herpes • Primary episode: acyclovi r 400 mg PO tid x 7 to 1 0 days or valacyclovi r 1 000 mg

PO bid x 7 to 1 0 days or famciclovir 250 mg PO tid x 7 to 1 0 days

•

•

•

Episodic recurrence: acyclovir 800 mg PO tid x 2 days or famciclovir 1 000 mg bid

x 1 day or valacyclovi r 500 mg PO bid x 3 days; if H IV pt, acyclovir 400 mg PO tid x 5 to 1 0 days or famciclovir 500 mg PO bid x 5 to 1 0 days or valacyclovir 1 g PO bid x 5 to 1 0 days Chronic daily suppression (J frequent sx outbreak 70%-80% if >6 recurrences! yr} : acyclovir 400 mg PO bid or famciclovi r 250 mg PO bid or va lacyclovi r 1 g PO q24h ; if H IV pt, acyclovir 400 to 800 mg PO bid or famciclovir 500 mg PO bid or valacyclovi r 500 mg PO bid Oral labial, normal host (start Rx with prodrome [tingling/burning] before lesion formation} : valacyclovi r 2 g PO q 1 2 h x 1 day or famciclovir 500 mg PO bid x 7

days or acyclovir 400 mg PO q4h x 5 days; Topical (penciclovir 1 % cream q2h x 4 days, acyclovi r 5% cream q3h x 7 days) • Oral labial, immunocompromised: acyclovir 5 mg/kg IV q8h x 7 days or famciclovi r 500 mg PO bid x 7 days or valacyclovir 500 mg PO bid x 5 to 1 0 days; acyclovir­ resistant H SV, IV foscarnet 90 mg/kg IV q 1 2 h x 7 days • Herpes whitlow: acyclovi r 400 mg tid PO x 1 0 days Clinical Pearl •

>85% of adu lts have serologic evidence of H SV- 1 i nfection. The seroprevalence of adults w/H SV-2 i n the Un ited States is 25%; however, only -20% of these pts recal l having sx of HSV infection .

c. Chancroid (Haemophilus ducreyi} Diagnosis H&P •

• •

•

•

•

One to three extremely pai nfu l u lcers accom panied by tender inguinal lymphadenopathy (especially if fl uctuant) ; chancroid typically soft i n com parison with the hard , pai nless chancre of syphilis. May manifest with inguinal bubo and severa l ulcers I n women: i n itial lesion i n the fourchette , labia m i nora, ureth ra , cervix, or anus; inflammatory pustu le or papule that ruptures, leaving a shal low, nonindurated ulceration, usually 1 - to 2-cm diameter with ragged, undermined edges U n i l ateral lymphadenopathy (50% pts) developing 1 wk later Rio syph i l i s (RPR, VDRL) in women because of the consequences of inappropriate Rx if pregnant Darkfield m icroscopy, H SV cultures, H. ducreyi culture

Treatment •

Pri mary: ceftriaxone 2 50-mg IM single dose or azithromycin 1 -g PO si ngle dose

249

• •

•

•

Alternative : ciprofloxacin 600 mg bid PO x 3 days or erythromycin base 500 mg qid PO x 7 days As H IV(+) pts have Rx fai l u re with single dose azithromyc i n , eval uate s/p 7 days Rx. Test all pts for H IV and syph ilis. Rx of sex partners if evidence of disease or have had sex with pt with in 1 0 days of presentation

d. Lymphogranuloma venereum (LCV) STD caused by C. trachomatis, serovars L 1 , L2 , or L3 . Diagnosis

•

• •

•

•

Serology; biopsy contraindicated because of the risk of sinus tract development

C. trachomatis cu lture , direct i m m unofl uorescence, or n ucleic acid detection

Mild leukocytosis with lymphocytosis or monocytosis, l ESR VDRL and H IV screening to r/o other STDs CT scan (suspected retroperitoneal aden itis)

H&.P •

Fi rst stage (incubation period 3-2 1 days) Primary lesio n : papule, shallow ulcer Herpetiform lesion at site of i noculation (most common) Women: posterior wal l , fou rchette, or vulva (most common)

• • • • •

•

Spontaneous healing without scarring

Second stage ( 1 -4 wk after primary lesion) • I nguinal syndrome: i ngu i nal adenopathy (uni lateral 70% cases) • Sx: painfu l , extensive adenitis (bubo) and suppuration with n umerous sinus tracts • "Groove sign " (femoral/i ngu i nal node i nvolvement -20%, men) • Female i nvolvement deep i l iac/retroperitoneal lymph nodes possi ble pelvic mass Th i rd stage (anogenital syndrome) • Subacute : proctocolitis • Late: tissue destruction/scarri ng, sin uses, abscesses, fistulas, strictures, elephantiasis

Treatment •

•

Pri mary: doxycycl i n e 1 00 mg PO bid x2 1 d Alternative : erythromyc i n 500 mg PO qid x 2 1 days or azith romycin 1 g PO q wk x 3 wk

0 MALE GEN ITAL TRACT INFECTIONS

a. Balanitis Rx: metronidazole 2 g PO x 1 or fl uconazole 1 50 mg PO x 1

•

b. Epididymo-orchitis Rx age 35 yr/homosexual men (insertive partners in anal intercou rse) • Primary: levofloxacin 500 to 750 mg IV/PO once daily or ciprofloxacin 500 mg

PO bid 1 0 to 1 4 days • Alternative: ampicillin-sulbactam 3 g IV q6h or piperaci l l in-tazobactam 3.375 g q6h

H. INFECTIOUS GI SYNDROMES

0 CLOSTRIDIUM DIFFICILE I NFECTION (CDI)

Diarrhea and bowel i nflammation associated with abx use. Sx range from ful m i nant diarrhea to leukocytosis associated with pseudomembranous colitis, mild to severe acute diarrhea , short-term colonization seen typically in health care fac i l ities, and recu rrent C D I with 60 days after i n itial Rx occurring i n 20% to 30% of cases . • H ighest-i ncidence pseudomembranous colitis: cephalospori ns • H ighest-i ncidence C D I : cli ndamycin ( 1 0% pseudomembranous col itis) • l Emergence of an epidemic virulent strain (NAP 1 /BI/027) Risk Factors

•

• •

250

•

•

• •

Adm i n i stration of abxs : can occur with any abx Prolonged hospital ization Advanced age Abd surgery Underlying disease (mal ignancy, renal fai l u re, debil itated status) Hospital ized, tube-fed pts PPI and H 2 blocker Rx

Diagnosis •

Sx: diarrhea , fever, and abdom inal cramps after abx use

Labs •

•

•

Stool assay for C. difficile toxins A and B (sensitivity of 85%, specificity of 1 OOo/o) . Fecal leukocytes : generally present in stool samples CBC (leukocytosis) . Sudden l i n WBC to >30,000/mm 3 may be indicative of ful m i nant colitis.

Treatment •

• •

•

• •

WBC < 1 5 ,000; no 11Cr • Primary: metronidazole 500 mg PO tid or 250 mg qid x 1 0 to 1 4 days • Alternative : vancomycin 1 2 5 mg PO qid x 1 0 to 1 4 days; teicoplanin 400 mg PO

bid x 1 0 days Sicker: WBC > 1 5 ,000, �50o/o l Cr • Pri mary: vancomycin 1 2 5 mg PO qid x 1 0 to 1 4 days Alternative: fidaxomicin 200 mg PO bid x 1 0 days Post-Rx relapse: • Fi rst relapse: metron idazole 500 mg PO tid x 1 0 days • Second relapse: vancomycin 1 25 mg PO qid x 1 0 to 1 4 days, then taper (wk 1 , bid; wk 2 , q24h; wk 3 , qod ; then q third day for five doses) Postop ileus (toxic megacolon) • Primary: metronidazole 500 mg IV q6h + vancomycin 500 mg q6h via NG tube Fecal transplantation (i ntesti nal m icrobiota transplantation [ I MT]) : eradication rate 94o/o. I nfusing intestinal microorganisms (in a suspension of healthy donor stool) into the intesti ne of a sick pt via enema, gastroscope/colonoscope , or nasojejunal tube restores the microbiota . Recurrence after i n itial episode is 20o/o to 2 5o/o regardless of i n itial abx; each recurrence l risk of repeat episodes (65o/o chance of recurrence after three CDI episodes) . Recurrent CDI is usually a relapse rather than re-infection, regardless of the time between episodes. =

•

IEJI SALMONELLA I NFECTION •

•

•

An estimated 1 m i l lion cases/yr of nontyphoidal salmonel losis occur i n the U n ited States. Approxi mately 500 cases of Salmonella typhi i nfection are reported each yr. Raw produce and contact with l ive pou ltry are central veh icles for salmonellosis.

Infections •

•

•

Local ized to Gl tract (gastroenteritis) Systemic (typhoid fever) Local ized outside of Gl tract

Diagnosis •

Gastroenteritis Incubation period: 1 2 to 48 h r Nausea, vomiting Diarrhea, abdom inal cramps Fever Bacteremia: occurs mostly in the immunocompromised host or those with underlying conditions, including H IV infection • Self-lim ited i l l ness lasting 3 or 4 days • Colonization of Gl tract persistent for months, especially in those treated with abxs

• • • • •

Typhoid Fever

Incubation period of few days to several wk Prolonged fever, often with a stepwise-increasing temperature pattern • Myalgias • Headache, cough , sore th roat • Malaise, anorexia • Abdominal pai n • Hepatosplenomegaly • Diarrhea or constipation early i n the course of i l l ness • Rose spots (faint, maculopapular, blanching lesions) sometimes seen on chest or abd Infections Outside G l Tract • Can occur in vi rtually any location • Usually occur in pts with underlying diseases 251 • Endocard itis, endovascular i nfections are caused by seed ing of atherosclerotic plaques or aneurysms •

•

•

• •

•

Hepatic or splenic abscesses in pts with u nderlying disease in these organs Urinary tract i nfections in pts with renal TB or schistosom iasis Salmonel lae a frequent cause of G ram(-) meni ngitis in neonates Osteomyel itis in children with hemoglobi nopath ies (particularly sickle cell disease)

Diagnosis •

Typhoid fever

• Cultures of blood, stool , urine. Repeat if i n itially (-) . • Blood cultures are more l i kely to be (+) early i n the cou rse of i l l ness. • Stool and urine cultures are more commonly (+) in the second and third wk of

i l l ness.

• H ighest yield is with bone marrow biopsy cu ltures: 90% (+) . • Serology using Wida l ' s test is hel pful in retrospect, showing a fourfold l i n •

•

convalescent titers. Gastroenteritis: stool cu ltures Extrai ntesti nal localized infection • Blood cultures • Cultures from the site of infection

Labs •

• •

Neutropenia is common. Transa m i n itis is possible. Culture to grow organism from blood , body fl uids, biopsy specimens.

Treatment •

•

Adequate hyd ration and electrolyte replacement in people with diarrhea Typhoid fever • Ciprofloxacin 500 mg PO bid or 400 mg IV bid for 1 4 days • Ceftriaxone 2 g IV qd for 1 4 days • If sensitive, may switch Rx to TM P/S MX 1 to 2 DS tabs PO bid or amoxicillin 2 g

PO q8h to complete 1 4 days • Dexamethasone 3 mg IV i n itially, followed by 1 mg IV q6h for eight doses for pts

with shock or �MS •

Gastroenteritis • Usually not indicated for gastroenteritis alone because this i l lness genera l ly

self-lim ited

• May prolong the carrier state • Prophylactic Rx for pts who are at h igh risk of developing compl ications from

• •

bacteremia (neonates, pts w/hemoglobinopathies, atherosclerosis, aneurysms, prosthetic devices, i m m unocompromised) Rx should be considered for those with persistently (+) stool cu ltures and for food handlers. S uggested regi mens for erad ication of carrier state • Ciprofloxacin 500 mg PO bid for 4 wk • TM P-S MX-DS 1 to 2 tab PO bid for 6 wk (if susceptible) • Amoxi c i l l i n 2 g PO q8h for 6 wk (if suscepti ble)

0 CAMPYLOBACTER I N FECTION

Etiology Campy/obacter jejuni (most commonly assoc . with gastroenteritis)

•

Clinical Findings • • •

Diarrhea , fever, abd pain onset several days after bacterial i ngestion Grossly bloody stools (< 1 0%) , occult blood (35%) Late com plications: reactive arth ritis, GBS

Diagnosis •

Stool culture

Treatment •

•

•

Typically self- l i m iting Macrolide indicated (high fever, frequent or bloody stools, pts at extremes of age/with comorbid conditions/i m m unocompromised or sx > 7 days) Table 8-3 com pares major food-borne pathogens.

0 SHIGELLA I NFECTION 252 Caused by one of several species of Shigella (most common cause of bacillary dysen­ tery in the U n ited States) . Shigella sonnei is the most commonly i solated species in the U nited States, and it usually causes m i ld watery diarrhea . Direct person-to-person

TABLE 8-3 • Major Food-Borne Microbes by the Prtndpal Presenting Gastrointestinal Symptom In Immunocompetent Adults

Vom iting Watery diarrhea

SourceNehicles

Organism

Staphylococcus aureus Bacillus cereus

Norovirus

Clostridium perfringens Enterotoxigenic Escherichia coli (ETEC)

Prepared food (e.g., sa ndwich es) Rice, m eat Shel lfish, prepared food All by contaminated food and water

Enteric viruses

Diarrhea with blood (dysentery)

Cryptosporidium parvum and Cryptosporidium ho minis Cyclospora cayetanensis Yersinia enterocolitica Vibrio cholerae Campylobacter jejuni Nontyphoidal Salmonella Enterohemorrhagic E. coli (usually serotype

0 1 57: H7 )

Nongastrointestina I manifestations

*

Shigella spp. Vibrio parahaemolyticus

Clostridium botulinum Paralysis from neuromuscu lar blockade Listeria monocytogenes Meningitis

Incubation Period

2-4 hr 1 -6 hr 24-48 h r 8-22 hr 24 hr Variable 5-28 days

Cattle and pou ltry: meat and milk Cattle and pou ltry: eggs , meat Cattle: meat, m i l k Contaminated food and water Contaminated seafood

7 days 2- 1 4 hr Hours-6 days 48-96 hr 1 2-48 h r 1 2-48 h r 24-48 h r 2-48 hr

Environment: bottled or canned food Contaminated packaged ch illed foods

1 8-24 h r U p to 6 wk

Diagnosis

Diagnosis u sually cli nical for all organisms

Stool culture

Stool culture

Toxin i n food or feces CSF culture

Recovery

50 yr or alcoholism/chronic disease (S. pneumoniae, Listeria , Gram [-] bac i l l i ) • Ampic i l l i n 2 g IV q4-6h + (ceftriaxone 2 g IV q 1 2 h or cefotaxime 2 g IV q4-6h) + vancomycin 1 5 mg/kg IV q8h (trough level 1 5-20 ll&'ml) + (dexamethasone 0 . 1 5 mg/kg IV q6h x 2-4 days; fi rst dose before or with fi rst dose abx) • * If severe �-lactam allergy: See the next subsectio n , on empiric Rx for (+) G ram sta i n , for alternative agents to cover suspected pathogens. Post-neurosurgery/ventriculostomy/l umbar catheter; penetrati ng trauma w/o basilar skul l fracture (S. epidermidis, S. aureus, facultative aerobic Gram [-] baci l l i ; P. aeruginosa a n d Acinetobacter baumannii) • Vancomycin 1 5 mg/kg IV q8h (trough level 1 5-20 ll&'m l) + (cefepime or ceftazidime 2 g IV q8h) • * If severe PCN/cephalosporin allergy, substitute either: aztreonam 2 g IV q6-8h or ciprofloxacin 400 mg IV q8- 1 2h • * If IV Rx i nadeq uate: i ntraventricular daily doses vancomycin 1 0 to 20 mg; amikacin 30 mg; tobramycin 5 to 20 mg; gentamicin 4 to 8 mg; colistin 1 0 mg; polymyxin B 5 mg • Trauma w/basilar skull fracture (S. epidermidis, H. influenzae, S. pyogenes) • Vancomycin 1 5 mg/kg IV q8h (trough level 1 5-20 ll&'m l) + (ceftriaxone 2 g IV

q 1 2 h or cefotaxime [Cefotax] 2 g IV q6h) + (dexamethasone 0 . 1 5 mg/kg IV q6h 2-4 days; fi rst dose with or before fi rst abx dose)

x

Empiric Rx: CSF Gram Stain (+} • Gram (+) diplococci (S. pneumoniae) • Primary: (cefotaxime 2 g IV q4-6h OR ceftriaxone 2 g IV q 1 2h) + vancomycin

•

•

•

1 5 mg/kg IV q8h (trough level 1 5-20 ll&'m l) + (ti med dexamethasone 0 . 1 5 mg/kg IV q6h x 2-4 days) • Alternatives: meropenem 2 g IV q8h or moxifloxaci n 400 mg IV q24h Gram(-) diplococci (N. meningitidis) • Primary: (cefotaxime 2 g IV q4-6h or ceftriaxone 2 g IV q 1 2 h) • Alternatives: PCN G 4 m i l l ion U IV q4h or ampici l l i n 2 g IV q4h or moxifloxacin 400 mg IV q24h or ch loramphenicol 1 g IV q6h Gram (+) baci l l i or coccobaci l l i (L. monocytogenes) • Primary: ampici l l i n 2 g IV q4h ± genta m i c i n 2 mg/kg loading dose then 1 . 7 mg/ kg IV q8h • * If PCN allergic: TM P-S MX 5 mg/kg (TM P comp) q6-8h or meropenem 2 g IV q8h Gram (-) baci l l i (H. influenzae, P. aeruginosa) • Primary: (ceftazidime or cefepime 2 g IV q8h) ± gentamicin 2 mg/kg IV first dose then 1 . 7 mg/kg IV q8h 259 • Alternatives: ciprofloxacin 400 mg IV q8- 1 2h; meropenem 2 g IV q8h; aztreonam 2 g IV q6-8h. Consider adding IV gentamicin to �-lactam or ciprofloxacin if resistance.

Prophylaxis for H. influenzae •

• •

Non pregnant adults: rifampin 600 mg q24h x 4 days Household: If one unvaccinated contact is s;4 yr old , give rifampin to all contacts except pregnant wome n . C h i l d care fac i l ities: If one case occurs and u nvaccinated c h i l d ren who attend a re s;2 yr old, consider prophylaxis + vacci nate; if �2 cases occur i n 60 days and u nvacci nated c h i ldren atten d , provide prophylaxis for a l l c h i ldren and personnel.

Prophylaxis for N. meningitidis

•

Close contact: ceftriaxone 250 mg I M four doses

x

1 dose or rifampin 600 mg PO q 1 2 h

x

0 VIRAL MENINGITIS

Acute febri le i l lness with signs and sx of meningeal i rritation, usually with a lympho­ cytic pleocytosis of the CSF and (-) CSF bacterial stains and cu ltures Etiology •

Enterovirus: 85% to 95% of a l l cases

Diagnosis •

CSF exa m i nation

• Usually shows pleocytosis • Lymphocytic predomi nance (neutroph ils i n early stages) • Opening pressure : 200 to 250 mm Hg • WBC : 1 00 to 1 000 mm 3 • l CSF protei n • l or n l CSF glucose • (-) G ram sta i n , cultures, C I E , latex aggl utination • Vi ral cultures or serologic testing may be diagnostic. • PCR for H SV, West Nile, or enterovirus (wh ich could shorten d u ration of abx Rx

and hospitalization if bacterial meni ngitis was suspected) H&P •

Fever, headache, nuchal rigidity, photophobia, myalgias

Imaging •

CT scan or MRI : If cerebral edema, focal neurologic fi ndi ngs develop.

Treatment •

No specific antiviral Rx for most viruses. Rx is supportive unless H SV is detected, which would be treated with IV acyclovir: 1 0 mg/kg q8hr i n adults; up to 20 mg/kg q8hr i n children < 1 2 yr old.

0 ENCEPHALITI S

a. Herpes simplex encephalitis

Acute febri le syndrome with evidence of meningeal i nvolvement and cerebel lar, cere­ bra l , or brainstem function dera ngement Diagnosis • •

•

•

•

•

LP: pleocytosis, usually lymphocytic (although neutrophils may be seen early on) , l CSF prote i n , nl or l CSF gl ucose, RBCs, and xanthochromia Selected tests on CSF fl uid i n viral encephalitis are described i n Table 8-5 . EEG changes showing periodic high-voltage sharp waves in the tempora l regions and slow wave complexes Temporal lobe involvement PMR that ampl ifies DNA from the CSF Classic herpetic skin lesions may be present.

H&P • •

• •

In itially, fever and evidence of meningeal i rritation Headache and stiff neck Later, development of signs of cortical dysfunction: l ethargy, coma, stupor, weakness, seizures, facial weakness, as well as brai nstem fi ndi ngs Cerebellar fi ndi ngs : ataxia, nystagmus, hypotonia, myoclonus, cranial nerve palsies, and abnl tendon reflexes

Treatment •

260

•

•

•

•

Supportive care Avoidance of i nfusion of hypotonic fl uids to m i n i m ize the risk of hyponatremia For pts who develop seizures: anticonvulsant Rx Acyclovi r 30 mg/kg/day IV total dose divided in q8h i ntervals 1 4 days Short courses of corticosteroids to control brain edema and prevent herniation

TABLE 8-5 • Selected Tests for Viral Encephalitis Organism/Syndrome

West Nile Virus

West Nile encephalitis Herpes Simplex Virus Type I

Herpes simplex encephalitis

Herpes Simplex Virus Type 2

Neonatal encephalitis

Relapsing meningitis Varicella-Zoster Virus

Meningoencephalitis Epstein-Barr Virus

EBV encephalitis

Test

Comment

lgM in CSF

Diagnostic of CNS invasive disease or acute flaccid paralysis

PCR in CSF CSF-serum antibody ratio

Sensitive and specific in the acute phase U seful 2 wk-3 mo after onset

PCR in CSF

Confirmatory, high sensitivity

PCR in CSF

Sensitive and specific in first 3 days of illness

PCR in CSF

Confirmatory when used with clinical and spinal fl uid findings; sensitivity unclear

PCR in CSF

Suggests CNS invasion by virus

PCR in CSF

Diagnostic but incompletely (70%) sensitive

PCR in CSF

Sensitive and specific

JC Virus

Progressive m ultifocal leukoencephalopathy

Cytomegalovirus

CMV ventriculitis

From Goldman L, Schafer AI: Goldman's Cecil Medicine, ed 24, Philadelphia, 20 1 1 Saunders.

b. West Nile Virus (WNV) Encephalitis

I nfected mosqu ito vector in midsummer to midautumn (maxi m u m mosquito i ntensity) Diagnosis H&.P •

•

Initial phase of i l l ness is nonspecific, with abrupt onset of fever accompanied by malaise, eye pain, anorexia , headache, and, occasionally, rash and lymphadenopathy. Less commonly, myocarditis, hepatitis, or pancreatitis may occur. In approxi mately 1 i n 1 50 cases, especially a mong elderly pts, severe neurologic sequelae (ataxia, CN palsies, optic neutitis, seizures, myel itis, polyradiculitis) occur.

Labs •

• •

CBC, electrolytes (hyponatremia common) LP: lym phocytic pleocytosis with n l level of glucose and l level of protei n CSF WNV lgM A b leve l : rare false(+) results in people recently vacci nated agai nst Japanese encephalitis or yellow fever vi ruses

Imaging •

CT or M R I studies of the bra i n to r/o mass lesions and cerebral edema

Treatment •

•

IV hydration, venti lator support may be necessary. No specific Rx is established (ri bavi rin and INF alfa-2b have i n vitro activity; IVIG under study) .

D BRAIN ABSCESS Etiology

•

•

• •

Contiguous focus of infection (55% of cases) : paranasal sinus i nfection (streptococc i , Bacteroides, Haemophilus, Fusobacterium) ; otitis media/mastoiditis (streptococc i , Enterobacteriaceae, Bacteroides, Pseudomonas) ; dental sepsis (Fusobacterium, Bacteroides, Streptococcus) ; penetrating head i nj u ry (5. aureus, Clostridium ) ; postoperative (5. epidermidis, S. aureus) Hematogenous spread (25% of cases) : endocarditis (5. aureus , viridans strep) ; CHD (streptococci , Haemophilus species) ; UTI (Enterobacteriaceae, Pseudomonadaceae) ; l ung (strep, Actinomyces, Fusobacterium) ; i ntra-abd (strep, Enterobacteriaceae, anaerobes) l m m u nocompromised host: Toxoplasma, fungi , Nocardia, Listeria, Enterobacteriaceae Cryptogenic (unknown source): 20o/o

261

Diagnosis H&P • •

Classic triad: fever, headache, and focal neurologic deficits depend i ng on location (50% of cases) Papilledema (2 5o/o)

Labs • •

• •

i WBC (60% of pts) . i ESR Blood cultures most often (-) (90%) LP contraindicated in pts w/suspected a bscess because of i ICP (20o/o die or suffer neurologic decline) Gram stai n/cu lture of material aspi rated at surgical drainage approaching 1 OOo/o

Imaging •

•

MRI of brain with and without gado l i n i u m C T w/IV contrast if M R I contraindicated

Treatment • •

• • •

•

•

•

•

•

•

If abscess 5 . 5 in RTA type 1 and 1 0 m Eq/L Gastrointestinal losses • vomiting • diarrhea • nausea Ileus/obstruction Skin losses • burns • open wounds Hemorrhage/blood loss

I Assess volume status I

II

Euvolemic Measure u rine osmolality

t

t

Renal causes >20 m Eq/L • Adrenal insufficiency • Mineralocorticoid insufficiency • Diuretics • Osmotic diuresis • Cerebral salt wasting

I

�

Hypotonic 290 mOsm/L • Hyperglycemia • Hypertonic infusions • Glycerol • Mannitol • Glycine

II

Extrarenal causes > 1 0 m Eq/L • Congestive heart failure • Cirrhosis • Nephrotic syndrome

I

11

Hypervolemic Measure urine sodium

t

Renal causes >20 m Eq/L • Renal failure

t

> 1 00 mOsm/L • S IADH • Adrenal insufficiency • Hypothyroidism

FIGURE 9-7 . Algorithm for treatment of hyponatremia (From Cameron AM: Current Surgical Therapy, l Oth ed. Philadelphia, Saunders, 201 1 .)

myelinolysis, this disease is now known also to affect extrapontine brain areas and i s known as osmotic demyelination syndrome. Man ifestations of myeli nolysis

usually evolve several days after correction of hyponatremia. Typical features are disorders of U M Ns, spastic quadriparesis and pseudobulbar palsy, and mental disorders ranging from mild confusion to coma. Death may occur. The motor and local izing signs of myeli nolysis differ from those of the general ized encephalopathy that is caused by u ntreated hyponatremia.

Clinical Pearls •

•

In genera l , the serum Na+ should be corrected only halfway to nl in the i n itial 24 hr (but not > 1 m Eq/Uhr) to prevent complications from rapid correction (cerebral edema, myeli nolysis, seizures) . A slower correction rate is indicated in pts w/ chronic hyponatremia. I n symptomatic pts w/hyponatre m i a , an i i n the serum Na+ concentration of 2 m Eq/Uh r to a level of 1 2 0 to 1 30 m Eq/L is considered safe by some experts; however, less rap i d correction may be i n d i cated i n pts w/severe or chronic hyponatre m i a .

IEJ HVPERNATREMIA Etiology

•

•

•

l sovolemic (! TBW, nl TB Na, and ECF) • Dl (neurogenic and nephrogen ic) • Skin loss (hyperemia), iatrogenic, reset osmostat Hypervolemic (TBW, TBNa, and ECF) • Iatrogenic (adm inistration of hypernatremic solutions) • M i neralocorticoid excess (Con n ' s syndrome, Cushing's syndrome) • Salt i ngestion Hypovolemic: loss of H 2 0 and Na+ (H 2 0 loss > Na+) • Renal losses (e.g. , di uretics, glycosuria) • G l , respi ratory, skin losses • Adrenal deficiencies

Diagnosis •

Figure 9-8 describes a diagnostic and treatment algorithm for hypernatremia.

287

HYPERNATREMIA Assess volume status

I

Hypovolemic 1 Measure u rine sodium t

< 1 0 m Eq/L Extrarenal causes • Sweating • G I Iosses • fistula • diarrhea • Respiratory • Burns

II

I

Euvolemic Measure u rine sodium

t

>20 m Eq/L • Iatrogenic . Hypertonic saline . Some IV antibiotics • Mi neralocorticoid • C ushing's • H ypertonic dialysis

>20 m Eq/L Renal causes • Diuretics • Glycosuria • Mannitol • U rea • Renal failure

I

t

I Hypo-/isotonic fluid I

...

< 1 0 m Eq/L • Diabetes insipidus • Central • Nephrogenic • Hypodipsia

I

Me

�

w

...

>20 m Eq/L • Insensible • Respiratory • Skin

Free water

I

I

Algorithm for treatment of hypernatremia. (From Cameron AM: Current Surgical Therapy, l Oth ed. Philadelphia, Saunders, 201 1.) FICURE 9-8.

Treatment lsovolemic Hypernatremia •

•

•

Fluid replacement w/D5W. Correct only half of estimated water deficit i n initial 24 hr. The rate of correction of serum Na+ should not exceed 1 m Eq/Uhr in acute hypernatremia or 0 . 5 m Eq/Uh r in chronic hypernatremia. Calculate water deficit i n hypernatremic pts. H 2 0 deficit (in l iters) 0 . 6 x BW (kg) x ([measured Na+/ 1 40] - 1 ) =

Hypovolemic Hypernatremia •

•

Fluid replacement i s achieved w/isotonic saline solution. The rate of correction of plasma osmolarity should not exceed 2 mOsm/kg/h r.

Hypervolemic Hypernatremia •

Fluid replacement w/D5W (to correct hypertonicity) is instituted after use of loop diuretics (to T Na+ excretion) .

F. DISORDERS OF POTASSIUM

HOMEOSTASIS 0 HYPOKALEMIA Etiology •

288

•

Cel lular sh ift (redistri bution) and undetermined mechanisms • Alkalosis (each 0 . 1 T in pH l serum K+ by 0.4-0 . 6 m Eq/L) • I nsulin administration • Vitamin B 1 2 Rx for megaloblastic anemias, acute leukemias • Hypokalemic periodic paralysis: rare familial disorder manifested by recurrent attacks of flaccid paralysis and hypokalemia • Beta adrenergic-Agonists, decongesta nts, bronchod ilators, theophyl line, caffeine • Bari um poisoni ng, tol uene i ntoxication, verapamil i ntoxication, chloroq uine i ntoxication • Correction of digoxin intoxication w/d igoxin Ab fragments (Digibind) Renal excretion • Drugs: diuretics, includ i ng carbonic an hydrase inhibitors (e.g. , acetazolamide) ; amphotericin B; h igh-dose Na+ PCN , nafc i l l i n , ampic i l l i n , or carben i c i l l i n ; cisplati n , AGs, corticosteroids, mineralocorticoids, foscarnet Na+

Rio medication-induced (e. g . , diu retics, J3 agonists, theophylline), prolonged d iarrhea, vomiting

I 1 0 mEq: d i u retics, Bartter's syndrome, mineralocorticoid excess (chloride unresponsive) • < 1 0 mEq: vom iti ng, gastric drainage (chloride responsive) • Measure BP; if l, consider mineralocorticoid excess. • Measure serum HC0 3 -: a l level is suggestive of RTA. ECG manifestations (Fig. 9- 1 0) • M i l d hypokalemia: flattening of T waves, ST-segment depression, PVCs, OT i nterval • Severe hypokalemia: promi nent U waves, AV cond uction disturbances, VT, VF

Treatment •

• • •

K+ replacement • PO K+ replacement is preferred . • IV i nfusion should genera l ly not exceed 20 m Eq/h r. Monitor ECG and urinary output. Identify the underlying cause and treat accord i ngly. IV N S solution is given i n chloride-responsive hypokalemia.

D HYPERKALEMIA Etiology

•

•

•

290

Pseudohyperkalemia • Hemolyzed specimen • Severe thrombocytosis (Pit count > 1 0 6 m l) • Severe leukocytosis (WBC > 1 os ml) • Fist clench i ng d u ri ng phlebotomy l K+ intake (often i n setting of i m paired excretion) • K+ replacement Rx • l K+ diet • Salt substitutes wfK+ • K+ salts of abx l Renal excretion • K+-sparing diuretics (e.g. , spironolactone, triamterene, amiloride) • Renal i nsufficiency • Mineralocorticoid deficiency • Hyporeninemic hypoaldosteronism (DM) • Tubular unresponsiveness to aldosterone (e.g. , SLE, MM, sickle cell disease) • Type 4 RTA • ACEis

HYPERKALEMIA

I Measure TTKG*I I

t

>5

I Renal failure I

Mineralocorticoid deficiency • Primary hypoaldosteronism • Addison's syndrome • Renin deficiency • Angiotensis II receptor blockers • AC E inhibitors • NSAI D • Heparin

Mi neralocorticoid resistance • Tubuloi nterstitial disease • Mineralocorticoid antagonists • Spi ronolactone • Trimethoprim • Othe r medications • Cyclosporine • Tacrolimus

I Excess intake I I Pseudohyperkalemia I I Transcellular shift I *Transtubular gradient = [K + ] u [K+] p X U asm

x

Pasm

The TTKG is typically 1 mo 2+ relapses within 6 mo Reduction of proteinuria to �0.20 g day- 1 and serum albumin >35 gl- 1

Pediatric Albu-stix 3+ or proteinuria >40 1 mg m-2 h- occurring on 3 days with in 1 wk 2+ relapses within 6 mo 1 35 gr 1

Reduction of proteinuria to between 0 . 2 1 g day 2 1 and 3.4 g day- 1 ± decrease in proteinuria of �50% from baseline Persistence of proteinuria despite predn isone therapy 1 mg kg2 1 day 2 1 x 4 mo

Disappearance of edema. Increase in serum a lbum in > 3 5 gl- 1 and persist­ ing proteinuria >4 mg m-2 h- 1 or 1 > 1 00 mg m-2 dayPersistence of proteinuria despite prednisone therapy 60 mg m 22 l x 4 wk

Two consecutive relapses occurring during therapy or within 1 4 days of completing steroid therapy

Two relapses of proteinuria within 1 4 days after stopping or during alternate day steroid therapy

From Floege J , John RJ, Feehally J (eds): Comprehensive Clinical Nephrology, 4th ed. Philadelphia, Saunders, 20 1 0. NS, Nephrotic syndrome.

* Definition of terms used in idiopathic nephrotic syndrome in adults and children. The defi n itions were generated by a consensus of the I nternational Society for Kidney Diseases in Children and the German Pediatric Nephrology Society. 1 0r persistence of proteinuria despite prednisone therapy 60 mg m-2 x 4 wk and three methyl prednisolone pulses.

TABLE 9- 1 0 • Summary of Primary Renal Diseases That Manifest as Idiopathic

Nephrotic Syndrome

Frequency

Minimal-Change Nephropathy Syndrome (MCNS)

Focal Segmental Sclerosis

Membranous Nephrotic

Type I

Type II

7 5% 1 5%

1 0% 1 5%

3 . 5 g/ 1 . 7 3 m 3/24 hr Blood chemistries: ! alb 1 0 g/24 hr (some pts may req u i re additional dietary protei n to prevent [-] n itrogen balance and sign ificant protei n malnutrition). I m proved urinary protein excretion and serum lipid changes have been observed w/!-fat soy protei n d iet providing 0 . 7 g of protei n/kg/day. However, because of the risk of malnutrition, many nephrologists recommend nl protei n i ntake . Na+ restriction for peri pheral edema Monitor for development of peripheral venous thrombosis and renal vei n thrombosis (risk related t o loss o f antithrombin I l l and other proteins i nvolved i n t h e clotting mechan ism) . Furosemide for severe edema ACEis to ! protein uria Anticoagulants as long as nephrotic proteinuria or alb level 40 yr 1 80, 000

Uver cysts Cerebral an eurysms Hypertension M itral valve prolapse Kidney ston es UTis Hepatic fibrosis Pulmonary hypoplasia Hypertension None

No

Ye s

MCKD

AD

Rare

Medullary DCT

No

Ye s

Retinal degeneration; neurologic, skeletal, hepatic, cardiac malformations Hyperuricemia, gout

MSK

No

1 : 5 , 000-20,000

Tuberous sclerosis

AD

VH L syndrome Oral-facial-digital syn drome-1 Bardet -Biedl syn drome

None

.

.

Nephrocystins (NPHP 1 -9) Uromodulin, oth ers None

Childhood or adolescence Adulthood 30s

Medullary C D

No

No

1 : 1 0,000

Hamartin (TSC 1 ) , tuberin (TSC2)

Childhood

Loop of Henle, DCT

Rarely

Rarely

AD

1 : 40,000

VH L protei n

20s

Cortical nephrons

Rarely

Rarely

XD

1 : 250 , 000

OFD 1 protein

Childhood or adulthood

Renal glomeru li

Rarely

Yes

1 : 65,0001 60 ,000

BBS 1 - 1 4

Adulthood

Renal calyces

Rarely

Yes

AR

.

Kidney stones Hypercalci uria Renal cell carci noma Tubers, seizures Angiomyol i poma Hypertension Retinal angioma, C N S hemangioblastoma, renal cell carcinoma, ph eoch romocytoma Malformation of the face, oral cavity, and digits; l iver cysts ; mental retardation Syn dactyly and polydactyly, obesity, reti nal dystrophy, male hypogen italism, hypertension , mental retardation

From Goldman L, Schafer AI [eds) : Goldman's Cecil Medicine , 24th ed. Philadelphia, Saunders , 20 1 2 . ACKD, Acquired cystic kidney disease; CD, coll ecting duct; OCT, distal convoluted tubule; MCKD, medull ary cystic kidney disease; MSK, medullary sponge kidn ey; TSC, tu berou s sclerosis complex; VHL, von Hipp ei-Lindau.

Imaging •

•

Plain fi lms of the abd can identify rad iopaque stones (Ca, uric acid stones) . Unen hanced (non-contrast-enhanced) helical CT scan has a sensitivity of 1 5% to 1 00% and a specificity of 94% to 96%.

Treatment • •

•

•

l Water or other fl uid i ntake (doubling of previous fl uid intake unless pt has h/o CHF or fl uid overload) Specific Rx tai lored to the stone type: • Uric acid calculi: control of hyperuricosuria w/al lopurinol 1 00 to 300 mg/day; urinary pH wfK+ citrate , 1 0-m Eq tablets tid • Co stones • Thiazide diuretic in pts w/type I absorptive hypercalciuria • l Bowel absorption of Ca w/cel l ulose P04- 3 1 0 g/day i n pts w/type I absorptive hypercalciuria • Orthophosphates to i n h ibit vita m i n B synthesis i n pts w/type I l l absorptive hypercalciuria • K+ citrate supplementation in pts w/hypocitratu ric Ca nephrol ithiasis • Purine dietary restrictions or al lopurinol i n pts w/hyperuricosuric Ca nephro l ithiasis • Struvite stones • Prolonged use of abx d irected against the predomi nant urinary tract organism may be beneficial to prevent recurrence. • Cystine stones • Hydration and alka l i nization of the urine to pH >6 . 5 with tiopronin or pen icillamine Surgical Rx i n pts w/severe pain unresponsive to medication and pts w/persistent fever or na usea or significant impediment of urine flow: • U reteroscopic stone extraction • ESWL for most renal stones Rx of ureteral stones: • Proximal ureteral stones 1 em in diameter: ESWL, percutaneous nephro ureterol ithotomy, ureteroscopy • Distal u reteral stones < 1 em in diameter (most of these pass spontaneously) : ESWL or ureteroscopy • Distal u reteral stones > 1 em in diameter: watchfu l waiting, ESWL, ureteroscopy (after stone fragmentation)

Clinical Pearls •

•

>50% of pts will pass the stone withi n 48 hr. Stones will recu r in 50% of pts with i n 5 yr if no medical Rx is provided.

305

A. DIAGNOSTIC AIDS 0 SPINAL DERMATOMES •

See Figure 1 0- 1 .

D KEY AREAS DETERMINING SENSORY LEVEL

•

See Box 1 0- 1 .

D KEY MUSCLES DETERMINING MOTOR LEVEL

•

See Box 1 0-2 .

0 GRADING OF MUSCLE STRENGTH •

See Table 1 0- 1 .

IJ G RADING OF DEEP TEN DON REFLEXES •

See Table 1 0-2 .

I) TESTING OF CRANIAL NERVES •

See Table 1 0-3 .

B. EPILEPSY 0 PARTIAL (FOCAL EPILEPSY)

Characterized by focal cortical discharges that provoke seizure sx related to the area of the bra i n i nvolved. Simple partial seizures do not cause i m paired consciousness, whereas complex partial seizures involve an alteration i n consciousness. Etiology

• •

Temporal lobe epilepsy (most common form epilepsy in adults) manifests as a complex partial seizure. Frequent causes of partial seizures are tumor, stroke, CNS i nfections (cysticercosis, abscesses) , AVMs, traumatic brain i nj u ry, cortical malformations, and idiopath ic/genetic conditions.

Diagnosis •

•

EEG Ambulatory EEG and/or video EEG if diagnostic uncertai nty

H&P •

•

Usually physical/neurologic exam is nl un less the cause is structural abnl ity (stroke) , wherein neuro exam is consistent with the area of CNS structura l damage . During partial seizures pts are conscious, unless there is spread of the epileptic focus causi ng secondary general ization and unresponsiveness. A focal seizure can evolve to a generalized ton ic clonic seizure. Table 1 0-4 describes clin ical man ifestations of different types of focal seizures and areas of the brain i nvolved.

Imaging • •

Head CT to r/o space-occupying lesions. If possible, avoid in children u n l ess an emergency. Bra i n MRI with defined epilepsy protocol should be performed if recurrent seizures.

Treatment •

•

306

•

•

Fi rst unprovoked seizure with nl imaging/EEG/labs genera l ly req uires no Rx; recu rrent or abnl w/up requ i res Rx with compliance; avoidance of EtO H and sleep deprivation is essential to prevent recu rrence. No driving is allowed unti l seizure freedom i n accordance w/local laws/regu lations (47o/o seizure free w/monoRx, 67o/o w/polyRx) . Avoid val proic acid (l risk teratogenicity) i n women of childbearing age and regardless of antiepi leptic drug taken; begi n folic acid ( 1 -4 mg/day) to prevent neural tube defects. Carbamazepine is the traditional i n itial drug for partial seizures.

' }::

. .. .. :: .

.:

' L4} f

FICURE 1 0- 1 . Spinal dermatomes. (From Green GM fed]: The Harriet Lane Handbook: A Manualfor Pediatric House Officers, 12th ed. St. Louis, Mosby-Year Book, 1 991.)

Box 10·1 • Key Areas Determining Sensory Level C2

Occipital protuberance

T6

C3

Supraclavicular fossa

T7-9

Sixth intercostal space, xiphisternum Intercostal spaces

C4

Top of the acromioclavicular joint

TlO

Umbilicus

C5

Lateral side of the antecubital fossa

Tll

Intercostal space

C6 C7

Thumb Middle finger

T12 Ll

Inguinal ligament Upper anterior thigh

C8

Little finger

L2

Midanterior thigh

Tl

Medial side of the antecubital fossa

13

Medial femoral condyle

T2

Apex of the axilla

T3

Third intercostal space

14 L5

T4

Fourth intercostal space, nipple line

Sl

Lateral heel

S2 S3 S4-5

Popliteal fossa in the midline Ischial tuberosity Perianal area

T5

Fifth intercostal space

Medial malleolus Dorsum of the foot at the third metatarsophalangeal joint

307

Box 10·2 • Key Museles Determining Motor Level C l-4

Diaphragm

C5 C6 C7

Elbow flexors (biceps) Wrist extensors Elbow extensors (triceps) Finger flexors, distal phalanx

cs

Tl

Hand intrinsics (interossei)

T2-Ll 12

Use sensory level and Beevor's sign Hip flexors (iliopsoas)

lA

Ankle dorsiflexors (tibialis anterior)

13

15 Sl 82-5

Knee extensors (quadriceps) Long toe extensors (extensor hallucis longus) Ankle plantar flexors (gastrocnemius) Use sensory level and sphincter ani

TABLE 1 0- 1 • Cradinc of Muscle Strength

Crade

Description

0 1 2 3 4

Absent muscle contraction M inimal contraction Active movement with gravity elimi nated Active movement against gravity only Active movement agai nst gravity and some resistance

5

Normal muscle strength

TABLE 1 0-2 • Cradinc of Deep Tendon Reflexes

Crade

Description

0 + ++ +++

Absent Hypoactive Normal Brisker than average

++++

Hyperactive, often indicative of disease

TABLE 1 0-3 • Testing of Cranial Nerves

Cranial Nerves

Sense of smell Vision (visual acuity, visual fields, color) Extraocular movement, pupillary constriction (oculomo­ tor) . elevation of upper lids, abduction of eye

v

VII VI I I IX X XI XII

Hypoglossal

Motor control of tongue

II Ill IV VI

308

Action

Olfactory Optic Oculomotor Trochlear Abducens Trigeminal Facial Acoustic Glossopharyngeal Vagus Accessory

Mastication; sensory of forehead, face, and jaw Facial expression; taste in anterior two thirds of tongue Hearing and balance Sensory and motor functions of pharynx and larynx (gag reflex, position of uvu la, swallowing) Shrugging of shoulders, movement of head, motor to trapezius, sternocleidomastoid

TABLE 1 0-4 • Clinical Manifestations of Different Types of Focal Seizures and

Areas of the Brain Involved

Seizure Type

Areas of Brain Involved

Clinical Expression

Somatosensory

Postcentral rolandic; parietal

Contralateral intermittent or prolonged tingling, numbness, sense of movement, desire to move, heat, cold, electric shock; sensation may spread to other body segments Contralateral agnosia of a limb, phantom limb, distortion of size or position of body part I psilateral or bilateral facial, truncal or limb tingling, numbness, or pain; often involving lips, tongue, fi ngertips, feet Contralateral regional clonic jerking, usually rhythmic, may spread to other body segments in jacksonian motor march; often accompanied by sensory symptoms in same area Bilateral tonic contraction of limbs causing postural changes; may exhibit classic fencing posture; may have speech arrest or vocalization Contralateral head and eye version, sal ivation, speech arrest or vocalization; may be combined with other motor signs (as above) depending on seizure spread Bi lateral or contralateral buzzing, drumming, single tones, muffled sounds Often described as unpleasant odor

Parietal Second sensory; supplemen­ tary sensory-motor Motor

Precentral rolandic

Supplementary sensory-motor

Frontal

Auditory Olfactory Gustatory Vertigi nous Visual

Limbic

Dyscogn itive

Heschl ' s gyrus-auditory cor­ tex in superior temporal lobe Orbitofrontal ; mesial temporal cortex Parietal; rolandic operculum; insula; temporal lobe Occipitotemporal-parietal junction; frontal lobe Occipital

Temporal; occipitotemporal­ parietal junction Limbic structures: amygdala, h ippocampus, cingulum, olfac­ tory cortex, hypothalamus

Usually bilateral involvement of limbic structures (see above)

Often unpleasant taste, acidic, metallic, salty, sweet, smoky Sensation of body displacement in various d i rections Contralateral static, moving, or flashing colored or uncolored lights, shapes, or spots; contralat­ eral or bilateral, partial or complete loss of vision Formed visual scenes, faces, people, objects, animals Autonomic: abdominal rising sensation, nausea, borborygmi , flushing, pallor, piloerection, perspi­ ration, heart rate changes, chest pain, shortness of breath, cephalic sensation, l ightheadedness, genital sensation, orgasm Psychic: deja vu, jamais vu, depersonal ization, derealization, dreamlike state, forced memory or forced thinking, fear, elation, sadness, sexual pleasure; hallucinations or i llusions of visual, auditory, or olfactory nature Previously known as "complex partial seizures, " characterized b y a predominant alteration of consciousness or awareness; current definition requires i nvolvement of at least two of five components of cognition: perception, attention, emotion, memory, and executive function

From Goldman L, Schafer AI (eds): Goldman's Cecil Medicine, 24th ed. Philadelphia, Saunders, 20 1 2 .

•

• •

Lamotrigine and leveti racetam are effective and well tolerated. Antiepileptics (lacosamide, oxcarbazepine, ezogabine) may be used by epilepsy special i sts. Surgery (temporal lobectomy i n mesial temporal sclerosis) may be indicated in refractory cases.

IIEJ IDIOPATHIC GENERAL EPILEPSY

Table 1 0-5 describes a classification and c l i n ical expression of general ized seizures. Diagnosis

• •

EEG Am bulatory EEG and/or video EEG if diagnostic uncerta i nty

309

TABLE 1 0-5 • Generalized Seizures: Classification and Clinical Expression

Seizure Type

Subtype

Clinical Expression

Absence

Typical

Abrupt cessation of activities, with motionless, blank stare and loss of awareness lasting "' 1 0 sec; the attack ends suddenly, and pt resumes normal activities immediately Longer duration than typical absence, often accompanied by myoclonic, tonic, atonic, and autonomic features as well as automatisms Absence with myoclonic components of variable intensity Sudden, brief (< 1 00 msec) , shocklike, involuntary, single o r multiple contractions of muscle groups of various locations A sequence consisting of a myoclonic followed by an atonic phase A sequence consisting of a myoclonic followed by a tonic phase Sustained increase in m uscle contraction lasting a few seconds to minutes Prolonged, regularly repetitive contractions involving the same muscle groups at a rate of 2-3 cycles/sec Sudden loss or diminution of muscle tone lasting 1 -2 sec, i nvolving head, trunk, jaw, or limb m usculature

Atypical

Myoclonic

With myoclonias Myoclonic Myoclonic-atonic Myoclonic-tonic

Tonic Clonic Atonic Ton ic-clonic

A sequence consisting of a tonic followed by a clonic phase

From Goldman L, Schafer AI (eds): Goldman 's Cecil Medicine, 24th ed. Philadelphia, Saunders, 20 1 2 .

Labs • •

Routi ne blood w/up (CBC, C M P , gl ucose , electrolytes) , urine tox screen LP recom mended if suspicion of meni ngitis

Imaging • •

Head CT scan r/o space-occupying lesions; avoid i n children u nless a neurologic emergency MRI of the brain epilepsy protocol performed in all pts with recurrent seizures

Treatment • • • •

•

Fi rst unprovoked seizure with nl imaging/EEG/Iaboratory w/u p req ui res no Rx; recurrent seizures or pts w/abnl w/up requ i re Rx based on type/etiology. Chronic Rx is indicated for more than two unprovoked seizures or in pts with one seizure with abnl w/up. Levetiracetam (initial dose 250-500 mg bid, max 1 500 mg bid) is an effective and well-tolerated antiepileptic drug for general ized tonic clonic seizures. Val proic acid (initial dose 1 0- 1 5 mg/kg/day div bid, max dose 60 mg/kg/day) is better tolerated than topiramate and more efficacious than lamotrigi ne i n pts w/general ized and unclassified epilepsy types; avoid valproic a c i d ( l risk teratogenicity) in women of childbearing age and regardless of antiepileptic drug take n ; begin folic acid ( 1 -4 mg/day) to prevent neural tube defects. No driving is allowed until seizure freedom i n accordance with local laws and regulations.

0 STATUS EPI LEPTICUS

Conti nuous seizure activity lasting �5 m i n or two or more discrete seizures w/i ncom­ plete recovery of consciousness between them . Diagnosis Convulsive status epi lepticus: Pts are unresponsive w/obvious tonic, clonic, or

• •

tonic-clonic extrem ity movements . Nonconvulsive status epilepticus varies from complete unresponsiveness w/ l ittle or no observable motor activity to confusion and/or repetitive behaviors/ automatisms; confirm dx by video EEG mon itoring or paradoxical i m provement i n ms after low-dose benzodiazepine.

Management •

Figure 1 0-2 describes a management algorith m for status epilepticus.

C. STROKE 0 TRANSIENT ISCHEMIC ATTACK (TIA)

3 1 0 Transient neurologic deficit resulting from focal bra i n , spinal cord , or retinal ischemia without acute i nfarction; sx typically 3 or those with transient monocular blind ness. Acute anticoagulation is indicated for new-onset AF and atheroth rombotic carotid disease causing recu rrent transient neurologic sx, especially before carotid endarterectomy (CEA) or carotid stenting. It is also considered for basilar a rtery thrombosis, given concern for progression to brainstem stroke w/h igh morbidity and mortal ity. Anti platelet therapy should be used to reduce the risk of recurrent TIAs or subsequent stroke. Three anti platelet agents are commonly used i n stroke prevention: aspiri n , aspiri n/d ipyridamole, and clopidogre l . All are reasonable choices, but practitioners should consider their individual pt's comorbidities when selecting an antiplatelet agent. Chronic therapy should be a i med at modifying the four major risk factors: BP contro l , control of dyslipidemia, control of blood sugar, and smoking cessation.

TABLE 1 0-6 • Characteristics of Thrombosis a n d Embolism

Thrombosis

Embolism

Onset of sx Hx of previous TIA Time of presentation

Progression of sx during hours to days Common Often during n ight hours while pt is sleeping Classically, pt awakens w/a slight neuro­ logic deficit that gradually progresses in a stepwise fashion

Very rapid (seconds) Uncommon Pt is usually awake and involved in some type of activity

Predisposing factors

Atherosclerosis, HTN , diabetes, arteritis, vasculitis, hypotension, trauma to head and neck

AF, mitral stenosis and regurgi­ tation, endocarditis , mitral valve prolapse

TABLE 1 0-7 • ABCD2 Risk of Stroke After a TIA

Age �60 yr BP: � 1 40 mm Hg systolic or 90 mm Hg d iastolic Clinical features U n ilateral weakness Speech disturbance without weakness Duration of TIA �60 min 1 0-59 min Presence of diabetes mellitus Two-day risk of stroke is 4. 1 % with a score 4-5 and 8. 1 % with a score 6-7 .

Score (points)

2 1 2 1

Modified from Ballinger A: Kumar & Clark's Essentials of Clin ical Medicine, 6th ed. Edinburgh, Saunders, 20 1 2 .

D ISCHEMIC STROKE

Rapid onset of neurologic deficit involving a certai n vascular territory secondary to thrombosis or embolism

Diagnosis H&P • Clin ical presentation varies w/the cerebral vessel i nvolved (Table 1 0-8) . 3 1 2 Imaging • I m m ediate CT of the head without contrast or M R I of the brain with stroke protocol to rule out hemorrhage and, if possi ble, to assess the extent of stroke . CT

TABLE 1 0-8 • Selected Stroke Syndromes

Artery Involved

Neurologic Deficit

Middle cerebral artery

Hemiplegia (UEs and face usually more involved than LEs) Hemianesthesia (hemisensory loss) Hemianopia (homonymous) Aphasia (if dominant hemisphere is i nvolved) Hemiplegia (LEs more involved than U Es and face) Primitive reflexes (e.g. , grasp and suck) Urinary incontinence I psilateral cranial nerve findings, cerebellar findings Contralateral (or bilateral) sensory or motor deficits

Anterior cerebral artery

Vertebral and basilar arteries Deep penetrating branches of major cerebral arteries (lacunar i nfarction)

Usually seen i n elderly pts with HTN and diabetic pts Four characteristic syndromes are possible: 1 . Pure motor hemiplegia (66%) 2. Dysarthria-clumsy hand syndrome (20%) 3 . Pure sensory stroke ( 1 0%) 4 . Ataxic hemiplegia syndrome w/pyramidal tract signs

of bra i n : area of l density; initial CT scan may be n l because the infarct may not be evident for 2 to 3 days afterward . Treatment • •

•

•

•

•

• •

IV TPA is the only medical therapy approved by the U . S . FDA for the treatment of acute ischemic stroke . The time wi ndow for administration is �3 h r of symptom onset. There are strict criteria for the admin istration of IV TPA (Box 1 0-5) . The protocol is weight based , with 9 0 m g being the maxi m u m allowable dose. The risk of brain hemorrhage with IV TPA is �5% i n pts w/stroke . M u ltimodal therapy ( i . e . , thrombectomy and i ntra-arterial TPA) is sometimes performed . Endovascular treatment may be performed for select cases in which IV TPA has fai led to recanal ize an occl uded artery. Endovascular intervention may be an option for pts w/systemic contraindications to IV TPA. Box 10-5 • Inelusion and Exelusion f:riteria for IV TPA lnelusion Criteria

1. 2. 3.

4.

Ischemic stroke onset i s within 3 hours of drug administration. Measurable deficit is noted on NIH S troke Scale examination. Pt's CT does not show hemorrhage or nonstroke cause of deficit. Pt' s is > 18 years old.

helusion Criteria (Absolute)

1. 2. 3.

4. 5. 6.

7.

8.

9.

10. 11. 12. 13.

14. 15.

Pt's symptoms are minor or rapidly improving. Pt had seizure at onset of stroke. Pt has had another stroke or serious head trauma within the past 3 months. Pt had major surgery within the last 14 days. Pt has known hx of intracranial hemorrhage. Pt has sustained S B P > 1 8 5 mm Hg. Pt has sustained D B P > 1 1 0 mm Hg. Aggressive treatment is necessary to lower the pt's B P . Pt has symptoms suggestive of SAH . Pt has had gastrointestinal or urinary tract hemorrhage within the last 2 1 days. Pt has had arterial puncture at noncompressible site within the last 7 days. Pt has received heparin with the last 48 hours and has elevated PTT. Pt's PT is > 1 5 sec. Pt's Pit count is < 1 0 0 , 0 0 0 J.!L. Pt's serum glucose is < 5 0 or >400 mg/dL.

helusion Criteria (Relative)

1. 2.

Pt has a large stroke with NIH S troke Scale score >22. Pt's C T shows evidence o f l arge MCA territory infarction (i.e., sulcal effacement o r blurring of gray-white junction in greater than o n e third o f M CA territory) .

NIH, National Institutes of Health.

Modified from Vincent JL, Abraham E, Moore FA, et al ( eds) : Textbook of Critical Care, 6th ed.

Philadelphia, Saunders, 20 1 1 .

313

•

•

•

Endovascular i ntervention is useful only for large , accessible thro m b i . Therefore, if a pt w/stroke is a candidate for IV TPA, then he or she should probably receive IV TPA. Anti platelet therapy: Begi n n i ng oral or feeding tube adm i n i stration of aspirin (325 mg/day) ::;48 hours of stroke onset is advised . Th is will decrease the l ikel i hood of a repeat ischem ic stroke. Another oral anti platelet regi men approved for secondary stroke prophylaxis (e.g. , clopidogre l , aspirin plus extended-release dipyridamole) will also suffice and may be superior i n the long term . l B P is common duri ng acute stroke , and it often subsides without specific Rx. In genera l , HTN is not treated acutely u n l ess it is extremely high (e.g . , >220 mm Hg SBP); u n less there is evidence of organ damage caused by the HTN ; or unless thrombolysis is bei ng considered, in which case BP needs to l (if it can be safely accom plished) to 1 85/ 1 1 0 m m Hg. It is risky to l BP severely the presence of acute ischemic stroke . A 1 5% to 25% decrease over the fi rst 24 hours is recommended. -

0 ACUTE HEMORRHAGIC STROKE a Intracranial hemorrhage

Neurologic deficit secondary to i ntracerebral hemorrhage ( 1 7% of a l l strokes) Etiology •

•

• • •

•

HTN (50%-60%) Cerebral amyloid angiopathy ( 1 0%) Hemorrhagic infarcts ( 1 0%) Use of anticoagu lants and fibrinolytic agents ( 1 0%) Bra i n tumors (5%) Vascular malformations (5%)

Diagnosis H&P •

•

Neurologic deficits vary w/the area i nvolved (Fig. 1 0-3 and Table 1 0-9) . Signs of l iCP (e.g. , bradycardia, l R R , third nerve palsy)

A2

Thalamoperforators

Circle of Willis. ACOM, anterior communicating artery; MCA, middle cerebral artery; PCA, posterior cerebral artery; PCOM, posterior communicating artery. (From Weissleder R, Wittenber-g J, Harisinghani M, Chen JW [ eds]: Primer of Diagnostic Imaging, 5th ed. St. Louis, Mosby, 201 1 .) FIGURE 1 0-3.

I maging • •

I m mediate: CT sca n n i ng of the head without contrast is h ighly sensitive for hemorrhage (area of hemorrhagic infarct appears as a zone of l density) . M R I of the brain with a gradient echo sequence is also h ighly sensitive for hemorrhage, includ i ng i ntracerebral microhemorrhages that may not be visible with CT scanning.

Treatment •

314

• •

•

Surgery should be performed promptly for cases of cerebellar hemorrhage of >3 em when the pt is deteriorating c l i nically or showing brainstem edema or hydrocephalus. Surgery for lobar or deep brain clots may be considered for select cases, although the level of evidence for efficacy is not h igh . Pneumatic compression devices should be applied to help prevent DVT. Early mobilization for rehabil itation is desirable.

TABLE I 0-9 • Localizing Signs in Pts w/lntracerebral Hemorrhage

Location of Intracerebral Hemorrha e Putamen

Thalamus

Pons

Cerebellum

Common Neurolo ic Si ns

Exam les

Both eyes deviating conjugately to the side of the lesion (away from hemiparesis) Pupils normal in size and reacting normally Contralateral hemiplegia present Hemisensory defect noted Both eyes deviating downward and looking at the nose Impairment of vertical eye movements present Pupils small ("'2 mm) and nonreactive Contralateral hemisensory loss present Both eyes i n midposition No doll's-eye movements Pupils pinpoint but reactive (use magnify­ ing glass) Coma common Flaccid quadriplegia noted

Left putamina! hemorrhage

--

. ...... c

�-�'-.....

�

-- ..�"..JA

Thalamic hemorrhage

(

- . .rl·

-. __

....

J.

..-r­ � :/�_;

Pontine hemorrhage

� --....

·"J _; _

Ipsilateral paresis of conjugate gaze (inabil­ ity to look toward side of lesion) Pupils normal in size and reacting normally Inability to stand or to walk Vertigo and dysarthria present

Box 10·6 • Suggested ReeoDUDended Guidelines for the Treatment of Ele-wated BP in Pts w/Spontaneous Intraeerebral Hemorrhage 1. 2.

3.

S B P of >200 mm Hg o r MAP of > 1 5 0 mm Hg: Consider the aggressive reduction of BP with continuous IV infusion, with B P monitoring every 5 min. S B P of > 1 80 mm Hg or MAP of > 130 mm Hg with evidence or suspicion of elevated ICP: Consider ICP monitor and reducing BP with intermittent or continuous N medications to keep cerebral perfusion pressure >60 to 80 mm Hg. S B P of > 1 80 mm Hg or MAP of > 1 30 mm Hg without evidence or suspicion of elevated ICP: Consider a modest reduction of B P (e.g. , MAP of 1 1 0 mm Hg or target BP of 1 60/90 mm Hg) with intermittent or continuous IV medications, and clinically reexamine the pt every 1 5 min.

Modified from Broderick J, Connolly S, Feldmann E, et al: Guidelines for the management of spontaneous intracerebral hemorrhage in adults: 2007 update. Stroke 38:2001-2023, 2007.

•

• • •

• • • •

HTN : BP should be qu ickly lowered by 1 5% and then grad ually and safely brought to the individual pt's target range. In theory, this may d i m i n ish expansion of the hematoma. Recommended guideli nes for Rx of HTN in pts w/spontaneous hemorrhage are described i n Box 1 0-6 . Hyperglycemia: A h igh blood gl ucose level predicts a worse outcome. Markedly elevated gl ucose levels should be lowered to 9 1 o/o of pts w/SAH have cardiac arrhyth mias) .

I m agi n g a n d La b s • •

•

•

CT of bra i n is (+) i n >95% of cases , especially during the acute phase ( i . e . , 24-48 hr) after the onset of bleedi ng. A CT angiogram or a cerebral angiogram is i m perative for determ i n i ng the origin of the SAH . Angiography may also be extremely useful because it may offer a therapeutic benefit via the coi l i ng of the aneurysm . Basic labs should i nclude CBC, chemistry panel, PT, PTI, Pit count, tropo n i n . L P is a very i mportant part o f t h e w/up, especially because 3o/o o f pts with normal CT scans show evidence of hemorrhage on LP. An RBC count of > 1 OO,OOO/m 3 strongly suggests SAH . If RBC counts ! between the fi rst and fourth tubes, then the tap is most l i kely traumatic. The presence of xanthochromia or bil irubin i n the CSF is a sign of SAH .

Treatment •

Management of SAH varies w/the pt's clin ical status (Table 1 0- 1 0) . as well as the location (see Fig. 1 0-3) and surgical accessibil ity of the aneurysm.

TABLE 1 0- 1 0 • Glasgow Coma Scale

Eyes

Motor

1. 2. 3. 4.

1. 2. 3. 4. 5. 6.

None To pain To speech Spontaneous

*

None Abnl extension Abnl flexion Flexion (withdrawal) Localizing Obeying commands

Verbal 1. 2. 3. 4. 5.

None Incomprehensible (groaning] Inappropriate Disoriented, confused Oriented

*The best score for each response should be documented and communicated in the format described above. Assessment of the best motor score is based on the best response of the arms. For use in individual pts, separate description of the three components of the GCS is strongly recommended. For purposes of classification, the total GCS can be calculated by adding the best score obtained in each category. The GCS should be annotated to indicate confounding factors: T signifies an i ntubated pt; 5, sedation; P, neuromuscular blockade. From Vincent JL, Abraham E, Moore FA, et al (eds): Textbook of Critical Care, 6th ed. Philadelphia, Saunders, 2 0 1 1 . • • • • •

316

• •

Pts with a depressed level of consciousness may need to be i ntubated and mechanically venti lated in an ICU setting. A l u m bar drain or ventriculostomy is req uired should the pt develop hyd rocephalus and l l C P . I n itial management strategies a r e geared toward stabi l izing t h e p t and preventing recu rrent hemorrhage and hydrocephalus. Tight BP control is paramount. This can be done with the use of drips (e.g. , nitroprusside) or PRN medications. An SBP 1 20 to 1 50 mm Hg is recommended. After an aneurysm has been identified, measures to secure it should be undertaken; this can be done by either cli pping or coi l i ng the aneurysm . Clipping consists of placing a clip around the neck of the aneurysm and is performed via i ntra-arterial angiography; it consists of deploying plati num coils inside the aneurysm to cause thrombosis of the aneurysmal sac. Pain control is performed with the use of short-acting and less-sedating medications (e.g. , codeine, low-dose morphine). Seizures occur i n :o;3o/o of pts during the acute phase; however, the use of prophylactic antiepileptics is sti l l controversia l .

•

Vasospasm, wh ich typically begi ns around day 3 after the hemorrhage and reaches a peak on day 6 to 8, is the leadi ng cause of death and disabil ity after aneurysm rupture. N i modipine has been shown to i m prove outcomes if it is adm i n i stered between days 4 and 2 1 after the hemorrhage, even if it does not sign ificantly reduce the amount of vasospasm detected on angiography. After vasospasm develops, "triple H" therapy-to achieve Hypertension, Hypervolemia, and Hemod i l ution-is used in an attem pt to provide adequate cerebral perfusion .

D SINUS VENOUS TH ROMBOSIS

Etiology Staphylococcus aureus (50%-60%) . Streptococcus (second leading cause) , gram (-)

•

rods/anaerobes; sphenoid sinusitis (most common site)

Diagnosis H&P •

• •

•

Ptosis, proptosis Chemosis CN palsies ( I l l , IV, V (VI and VI I ) , VI); VI is most common Sensory deficits of the ophthalmic/maxi llary branch of the fifth nerve are com mon.

Labs • •

CBC, ESR, blood/sinus cultures (identify infectious primary source) LP necessary to r/o meni ngitis

Imaging •

M RV, M R I w/gadol i n i u m including M R angiography

Treatment •

•

Rx should take i nto account the primary source of i nfection , as wel l as possible associated com plications, such as brain abscess, meningitis, or subdura l empyema. Broad-spectrum IV abx are used as empiric Rx until a defi nite pathogen is found. Rx should include a penici l l inase-resistant PCN at maximum dose plus a th i rd- or fou rth-generation ceph : • Nafc i l l i n (or oxac i l l i n) 2 g IV q4h plus either ceftriaxone (2 g q 1 2h) or cefepime (2 g q6h) • Metronidazole 500 mg IV q6h should be added if anaerobic bacterial i nfection is suspected (dental or sinus i nfection). • Vancomyci n (1 g q 1 2 h w/n l renal fu nction) may be substituted for nafc i l l i n if significant concern exists for i nfection by M RSA or resistant Streptococcus pneumoniae.

•

•

• •

•

Anticoagulation w/hepari n : controversia l . Cerebral infarction or ICH should fi rst be ruled out by non-contrast-enha nced CT scan before i n itiation of hepari n Rx. Current recommendation is for early heparin ization i n pts w/un i l ateral CST to prevent clot propagation and to i the i ncidence of septic embol i . Warfarin Rx should be avoided in the acute phase of the i l l ness but should ultimately be instituted to achieve an I N R of 2 to 3 and contin ued u nti l the i nfection, sx, and signs of CST have resolved or significantly i m proved. Steroid Rx: controversial but may prove hel pfu l i n ! cranial nerve dysfu nction or when progression to pituitary insufficiency occurs. Corticosteroids should be instituted only after appropriate abx coverage . Dexamethasone 1 0 mg q6h is the Rx of choice. Emergency surgical drainage w/sphenoidotomy: indicated if the primary site of infection is thought to be the sphenoid sinus. All pts w/CST are usually treated w/prolonged courses (3-4 wk) of IV abx. If there is evidence of com plications such as i ntracranial suppuration, 6 to 8 wk of total Rx may be warranted . All pts should be mon itored for signs of complicated i nfection, conti nued sepsis, or septic emboli while abx Rx is being admin istered.

D STROKE PREVENTION : ASYMPTOMATIC CAROTID STENOSIS Carotid stenosis is narrowing of the arterial lumen with i n the carotid artery. Etiology •

•

•

•

•

Atherosclerosis (most common) Aneurysm Arteritis Carotid dissection Fibromuscular d isplasia

317

•

• •

Postradiation necrosi s Vasospasm Risk factors : HTN , dysl ipidemia, DM, and smoking

Diagnosis •

Carotid d uplex. If carotid stenosis is suspected on carotid d uplex, but resu lts are inconcl usive, M R I , CT angiography, or traditional angiography should be obta i ned to confirm the degree of stenosis.

H&P

Pts with carotid stenosis are often asymptomatic, but many have presence of a carotid bruit or TIA. Treatment (Table 1 0- 1 1 ) • CEA and carotid angioplasty and stenting are avai lable. • CEA: The selection of surgical candidates should be guided primarily by the presence or absence of symptoms and the degree of stenosis. •

Asymptomatic Pts • •

•

CEA should be considered in asymptomatic pts only if the perioperative risk for stroke and death at the given surgical institution is 5 yr and the perioperative stroke and mortal ity rates a re 5 yr and perioperative risk for mortality i s 5 yr and perioperative risk of mortality is 65 yr

Years, up to a decade

Normal until advanced stage

From the 30s

Years

Normal until advanced stage

Personality change Disinhibition Obsessions and compulsions "Alien stare" Amnestic memory loss later Visuospatial i ntact Early falls Visual hallucinations Neuroleptic sensitivity Fluctuating course Limb apraxia "Alien hand" Visual spatial deficits Retrieval memory loss Depression Slowness Stepwise progression

45-65 yr

Years

Normal until advanced stage

>50 yr

Months to years

>60 yr

Years

>65 yr

Years

Any age

Months

Early extrapyram idal signs, with rigidity greater than tremor Apraxia Rigidity Myoclonus Focal neurologic deficits Rigidity and cogwheeling Gait abnlity Gait abnlity Hyperreflexia (legs > arms) Babinski 's signs

Familial Alzheimer's disease Frontotemporal dementia

Lewy body dementia

Corticobasal gangl ionic degeneration Vascular dementia

Normal-pressure hydrocephalus

Retrieval memory loss Urinary incontinence Progressive gait difficulty Slowness Visuospatial i nfarct

-

From Goldman L, Ausiello D (eds) : Cecil Textbook of Medicine, 22nd ed. Philadelphia, Saunders, 2004.

caregiver about the noni ntentional nature of the psychotic features , behavior modification, mai ntenance of routi nes, and envi ron mental safety. Effective medications for long-term use i n pts w/behavioral problems associated w/dementia are risperidone and olanzapine. • Donepezil , rivastigm ine, and galantamine are reversible acetylcholi nesterase inhibitors approved for Rx of mild to moderate dementia of Alzheimer's type. They may be hel pful in delayi ng the progression of Alzheimer's disease if used in the early stages. They can provide modest improvement of sx and temporary stabil ization of cogn ition by lengthening the time from assisted com m u n ity l iving to nursing home placement. Memantine is an N-methyl-o-aspartate ( N M DA) receptor blocker ind icated for the Rx of moderate to severe Alzheimer's disease. It can prod uce sl ight improvements in cogn itive performance. The c l i n ical significance of these improvements is sma l l . Memantine can be used i n combi nation w/ anticholinesterase i n h ibitors.

G. MULTIPLE SCEROSIS (MS) Chronic autoimmune demyeli nating disease of the CNS characterized by c l i n ical at­ tacks (relapses) correlated w/lesions separated in time and space . A relapse is the subacute onset of neurologic dysfu nction that lasts for �24 hr. Subtypes of M S include the fol lowing: relapsing-remitting MS (RRMS}, relapses followed by complete or nearly com plete recovery; secondary progressive MS (SPMS}, progression of disabil ity w/ few or no relapses; and primary progressive MS (PPMS}, progression from onset. Rare MS variants include the fol lowing: Bolo 's concentric sclerosis, alternating ri ngs of myel i nation and demye l i nation ; Marburg 's disease, tumor-like lesion w/sign ificant edema; and Schilder's diffuse sclerosis, childhood onset w/one to two large , symmetric lesions. Neuromyelitis optica (Devic's disease) i nvolves primarily the optic nerves and 327 spinal cord and is considered a separate disease. Table 1 0- 1 6 summarizes the McDonald criteria for M S .

TABLE 1 0- 1 6 • Summary of Revised 2005-20 1 0 McDonald Criteria

for Dlaposls of MS

Clinical Attacks

Clinical Lesions

2 2

2

2 1

Paraclinical Testing Needed None M R I dissemination in space or two lesions on MRI consistent with M S plus positive CSF M R I dissemination in time M R I dissemination in space or two M R I Iesions consistent with M S and positive CSF and M RI dissemination i n time

Evidence of clinical lesions by physical exami nation or evoked potentials. Diagnosis of PPMS: 1 year evidence of disease progression and two of the following:

( 1 ) evidence for dissemination in space, (2) evidence for dissemination in time, or (3) positive CSF MRI dissemination in space, by either ( 1 ) one or more T2 lesion in two of the four typical areas for MS lesions (periventricular, j uxtacortical, infratentorial, or spinal cord) or (2) awaiting further clinical attack implicating a distinctly separate CNS region. MRI dissemination in time, a new enhancing lesion �3 mo or a new nonenhancing lesion �6 mo after the initial attack; positive CSF, positive oligoclonal bands or elevated immunoglobulin G index. Modified from Degenhardt A: Ferri 's Cli nical Advisor, 20 1 3. St. Louis, Mosby, 20 1 2, p. 700. I n corporates 20 1 0 Revi­ sions to Diagnostic criteria of MS (for details, please see original article: Polman CH, Reingold SC, Banwell B. et al: Diagnostic criteria for multiple sclerosis: 20 1 0 revisions to McDonald's criteria. Ann Neurol 69:292-302, 20 1 1 ) .

Diagnosis •

•

•

M S : based on revised 2005 McDonald criteria (see Table 1 0- 1 6) RRMS: at least two relapses-two clin ical lesions distinctly separated in space and time or one clin ical lesion plus paraclin ical testing PPMS: insidious progression of disabil ity with a positive CSF and either dissemi nation i n both space and time or ongoing progression for ;::: 1 yr

H&.P •

•

• • • •

Visual abnl ities • Paresis of medial rectus muscle on lateral conj ugate gaze (i ntern uclear ophthalmoplegia) and horizontal nystagm us of the adducting eye • Central scotoma , ! visual acu ity (optic neuritis) • A Marcus Cunn pupil (pupil that paradoxically dilates w/d irect l ight) . indicating damage to the optic nerve anterior to the chiasm, is frequently present. • Nystagm us Abn l ities of reflexes • l DTRs • (+) Hoffmann's sign , (+) Babinski 's reflex • ! Abd skin reflex, ! cremasteric reflex Lhermitte 's sign: flexion of the neck while the pt is lying down elicits an electrical sensation extending bi laterally down the arms, back, and lower trunk. Uhthoff's phenomenon: exercise- or heat-induced deterioration of function Charcot's neurologic triad: nystagmus, sca n n i ng speech, and intention tremor I m paired recogn ition of objects by touch alone (astereognosis)

Imaging • • •

MRI of brain w/gado li ni um can identify lesions as small as 3 to 4 m m and is used to assess disease load, activity, and progression. M R I reveals multiple, predominantly periventricular plaques; however, normal M RI can not be used to exclude M S . MRI o f t h e cervical s p i n e c a n also be helpfu l .

Labs •

328

•

•

LP for all first relapses when the dx of MS is not defi n ite . Possible CSF abnl ities include l protein and mononuclear WBCs (both usually only m i l d ) . CSF lgG index and (+) ol igoclonal bands are seen in 7 0% and 90%, respectively, of clin ically defi nite M S cases. False(+) results occur w/lgG index i n CNS infections and i nflam mation but rarely w/ol igoclonal bands. Serum : CBC, ESR, CRP, CHEM 7, LFTs, ANA, vita m i n 8 1 2 . Lyme titer, TSH Consider evoked potentials (VEP, SSEP, BAER) : Demyeli nation will slow cond uction velocities.

Treatment Acute General Rx •

•

Relapses: h igh-dose IV methyl predn isolone (3-5 days of 1 g/day; alternative dose is 1 5 mg/kg/day) , often followed by a 7- to 1 0-day predn isone taper. No evidence suggests that h igh-dose corticosteroids alter the long-term course of disease. If pt has marked acute disabil ity and acute corticosteroid therapy has failed , plasma exchange ( 5 to 7 exchanges o n alternate days) have shown benefit.

Chronic Treatment

Disease-mod ifying therapy: incl udes i nterferon-� 1 a, interferon-� 1 b, and glati ramer acetate. I nterferons require routine CBC and LFT checks (initially i n 1 mo, q3mo thereafter) , occasionally TS H . None are needed with glatiramer acetate . Interferons can frequently cause fl u l i ke sym ptoms. • Fingoli mod, a sphi ngosine- 1 -phosphate receptor modulator, is approved as the fi rst oral disease-modifying agent. Common side effects are l iver toxicity, bradycardia with the fi rst dose only, and pancytopen ia. Its use may be reasonable in pts who cannot tolerate or do not benefit from alternative disease-modifying therapies and i n those who have had one or more relapses or new wh ite-matter lesions on M R I with i n the past year. • Dalfampridine is a potassium channel blocker approved to i mprove walking speed in patients with M S . • Cytotoxic: Methotrexate or azath ioprine is occasionally used i n R R M S o r P P M S . Consider cyclophosphamide or m itoxantrone (causes dose-dependent card iotoxicity) for frequent relapses with sign ificant disabil ity progression and for early secondary progressive M S . Emerging potential agents with long-term i m m unosuppressive effects include cladribine, alemtuzumab, dacl izumab, laq u i n i mod, and terifl u nomide. • Monoclonal antibodies: Natal izumab is approved for treatment of RRMS i n t h e form o f monthly i nfusions. It h a s been associated with an i ncreased risk of developing progressive m u ltifocal leukoencephalopathy (rare and fatal brain infection). Pts taking natal izumab m ust enter i nto a registry for mon itori ng. • Spasticity: Onabotul i n u m toxin type A i njection is FDA approved as fi rst-line therapy for upper l i m b spasticity. Baclofen, tizanidine, dantrolene diazepam , lorazepam, a n d intrathecal baclofen are other alternatives. • Pai n : carbamazepine, gabapenti n , or am itri ptyl ine • Spastic bladder: oxybutyn i n , tolterodine, or propantheline; prazosin for spastic sphincter • Fatigue: Consider amantadine 1 00 mg bid, modafi n i l (most effective for somnolence) , or fl uoxeti ne. • Tremor: clonazepam , carbamazepine, propranolol , or gabapentin. Wrist spli nts may be helpfu l . •

H. DISORDERS OF THE SPINAL CORD 0 COMPRESSIVE MYOPATHIES •

Spinal cord compression is the neurologic loss of spine function. Lesions may be complete or incomplete and develop gradually or acutely. Incomplete lesions often are man ifested as distinct syndromes, as follows: • Central cord syndrome • Anterior cord synd rome • Brown-Sequard syndrome • Conus medullaris syndrome • Cauda equina syndrome

Etiology •

• •

•

•

•

•

Trauma Tumor Infection Inflammatory processes Degenerative disk conditions w/spinal stenosis Acute disk herniation Cystic abnl ities

Diagnosis H&P •

Clinical features reflect the amount of spinal cord i nvolvement: • Motor loss and sensory abnlities

329

• •

•

• •

• (+) Babinski 's reflex • Clonus • Gradual compression: manifested by progressive difficulty walki ng, clonus w/ weight bearing, and invol untary spasm; development of sensory sx; bladder dysfunction (late) Central cord syndrome: variable quadriparesis, w/UEs more severely involved than the LEs; some sensory sparing Anterior cord syndrome: motor, pai n , and temperature loss below the lesion Brown-Sequard synd rome • Caused by injury to either half of the spinal cord and resulting i n the loss of motor fu nction, position, vibration, and l ight touch on the affected side • Pain and temperatu re sense loss on the opposite side Conus medul laris syndrome: variable motor loss i n the LEs w/loss of bowel and bladder function Cauda equina syndrome: typical low back pai n , weakness in both LEs, saddle anesthesia, and loss of vol untary bladder and bowel control

Imaging •

MRI

Treatment •

U rgent surgical decompression

0 I N FECTIOUS MYOPATH IES

• •

• •

•

•

H IV infection Viral myositis Trichi nosis Toxoplasmosis Cysticercosis Bacterial i nfections

0 I N FLAMMATORY MYOPATHIES • • • • •

•

• •

•

•

SLE, RA Sarcoidosis Paraneoplastic syndrome Polymyositis, dermatomyositis Polyarteritis nodosa M CTD Scleroderma Inclusion body myositis Sjogren's syndrome Cimetidine, D-penicillamine

0 ENDOCRINE-RELATED MYOPATHIES Corticosteroid-Induced Myopathy

•

Proximal l i m b weakness (mostly legs) in chronic corticosteroid pts

Demographics •

•

Women affected x2 as men i Risk use h igh-dose (�30 mg/day) prednisone

Diagnosis •

• •

•

Cushi ngoid body habitus Neurologic exa m : i ntact ocular, facial, distal extremity strength ; n l sensory exam and DTRs Labs: serum CK and EMG results nl (i CK or abnl EMG suggests recu rrence of partly Rx myositis or another myopathy) M uscle biopsy: non-dx, only shows atrophy type l i b muscle fibers

Treatment •

Slow tapering of corticosteroid Rx with discontinuation

Thyrotoxic Myopathy •

Sym metric muscle weakness in pts with classic hyperthyroidism or hypothyroidism

Clinical and Presentation and Treatment •

330

If hyperthyroidism (m uscle atrophy/fasciculations) VS hypothyroidism (muscle hypertrophy) • Serum CK level and EMG usually n l • Correct endocrine disorder to resolve myopathy

Toxic Myopathies •

•

Clin ical presentation of proximal m uscle weakness, myalgia, and cramps should prom pt review of current med ications (statins) as a recent T dosage , switc h , or addition can T myopathy risk. Concom itant use of drugs that i n h i bit CYP3A4 (macrolides, cyclospori ne, itraconazole, protease i n h i bitors) will T risk myopathies in pts taking lovastati n , si mvastatin, atorvastati n . I n these pts, pravastatin, rosuvastati n , or fl uvastatin (differently metabol ized) may be preferable.

D IDIOPATHIC TRANSVERSE MYELITIS

Demyeli nation in a transverse region of the spinal cord due to an inflam matory pro­ cess leadi ng to sensory and motor changes below the lesion Etiology

•

Demyeli nation due to the body's immune response to infection, post-vaccination , may be onset of m u ltiple sclerosis (MS), or may be idiopath ic ( 1 5%30% of cases) . • About 50% of pts have had a recent U R I . • EBV a n d C M V are most common viral i nfections. • Hepatitis B , varicella, enterovi rus, rhi novi rus, mycoplasma, syph ilis, measles, Lyme disease are less common.

Diagnosis •

• •

Transverse mye l itis should be suspected in pts with a hx of rapid (hr to days) onset of motor weakness, sensory abnl ities referable to the spinal cord , and bladder or bowel dysfunction. The dysfunction is bilateral (not necessarily symmetric) and there is a clearly defi ned sensory leve l . L P looking for ol igoclonal bands for M S or infection MRI of brain and MRI of spine at level of suspected i nvolvement

H&.P •

•

•

•

The clin ical signs are caused by an i nterruption in ascending and descend i ng neuroanatomic pathways i n the transverse plane of the spinal cord and a resulting sensory level is characteristic of transverse myelitis. Rapid onset of symmetric or asymmetric paraparesis or paraplegia of the lower extrem ities over a few days, ascending paresthesia, trunk sensory leve l , back pai n , sphincter dysfu nction, a n d (+) Babinski with upgoing toes bi laterally. The arms may also be i nvolved but < the legs i n most cases. One th ird to one half of pts present with localizing back pa i n . There is progression t o n a d i r o f clin ical deficits between 4 h r a n d 2 1 days after symptom onset.

Labs •

• • •

•

CSF: T protein/n l prote i n , lymphocytes, and nl glucose Serum N M O-IgG to w/up neuromyelitis optica, which should be ruled out. Ol igoclonal bands should be absent in CSF in transverse myelitis and (+) in M S . Liver enzymes m a y help t o differentiate if it is posti nfectious transverse myel itis versus M S . Consider a utoimmune w/up for lupus.

Treatment •

• • •

H igh-dose IV corticosteroid (e.g. , methyl predn i solone 1 000 mg/day for 3-5 days) Rescue Rx with plasma exchange may be hel pful in pts who do not respond to corticosteroids. Combi nation Rx with plasmapheresis and i m m unosuppressive agents (e.g. , cyclophospham ide) may also be effective. Naproxen , ibuprofen for pai n

I. PERIPHERAL NEUROPATHIES 0 GENERAL APPROACH

Figure 1 0-4 describes a systematic approach to eval uate neuropathy.

IIEJ MONONEUROPATHIES a Carpal Tunnel Syndrome

Com pressive neuropathy of the median nerve as it passes under the transverse carpal l igament at the wrist. It is the most common entrapment neuropathy. Diagnosis •

Pai n , paresthesia in the fi rst, second, and third fi ngers and the lateral half of the fou rth finger, worse at n ight

331

Acute AIDP Diphtheria

Diabetic CIP HIV Medsffoxins

Vascu litic Diabetic

FIGURE 1 0-4. A systematic approach to evaluate neuropathy. The diseases listed are examples of neuropathies associated with specific neurophysiologic and clinical findings. Diabetic distal, predominantly sensory neuropathies are manifested as chronic axonal neuropathies; acute asymmetric neuropathies can also occur with diabetes. Most neuropathies caused by toxins or by side effects of medication are chronic, symmetric axonal neuropathies. Acute inflammatory demyelinating polyradiculoneuropathy (AIDP), acute motor axonal neuropathy (AMAN), and acute motor and sensory axonal neuropathy (AMSAN) are subtypes of Guillain-Barre syndrome. These and other examples are discussed in more detail in the text. CIDP, chronic inflammatory polyradiculoneuropathy; CIP, chronic illness polyneuropathy; CMTl , Charcot-Marie-Tooth disease type 1, a genetic disorder; ENMG, electroneuromyography; HIV, human immunodeficiency virus-related neuropathy; a-MAG, anti-myelin-associated glycoprotein; MMN, multifocal motor neuropathy. (From Goldman L, Schafer AI [ eds}: Goldman 's Cecil Medicine, 24th ed. Philadelphia, Saunders, 2012.)

• •

•

Tine/ 's sign at wrist: Tapping l ightly over the median nerve on the volar surface of the wrist produces a tingling sensation rad iati ng from the wrist to the hand. Phalen's sign: reproduction of sx after 1 m i n of gentle, unforced wrist flexion EMG: impaired sensory conduction across the carpal tunnel

Treatment •

•

• •

•

•

Activity modification Nocturnal wrist spl i nt Corticosteroid i njection of carpal canal on ulnar side of palmaris longus tendon proxi mal to wrist crease Short-term benefit from U/S Rx Ergonomic keyboards (vs standard keyboards) Surgery in refractory cases b Bell's Palsy

Acute peri pheral facial (seventh) nerve palsy Etiology •

H SV is thought to be the most common viral pathoge n , followed by herpes zoster.

Diagnosis •

Onset is usually acute to subacute over hours of unilateral facial paralysis with maximal weakness at 3 wk. One third of pts demonstrate incomplete paralysis, whereas the remaining two thirds have complete paralysis. Recovery is present with i n the fi rst 6 mo.

Treatment

332

•

•

Glucocorticoid Rx: prednisone 60 to 80 mg/day for 1 wk Started at �72 hr shortens recovery time and i o/o of pts with complete recovery. Use of valacyclovir not recommended (Rx efficacy did not differ from placebo) . No added benefit was seen with combi nation Rx.

Disposition

• 7 1 % of pts : complete recovery • Recurrence rate is 7%. Average time to recurrence is 1 0 yr.

D POLVNEUROPATH IES a Diabetic Neuropathy Diagnosis

• EMG can be helpful in confirming the presence, extent, and severity of neuropathy. H&P

• Distal symmetric polyneuropathy (DSPN) • Pts most commonly experience numbness and tingling but may also experience feel i ngs of tightness or a sensation of heat or cold. • Pain is not uncommon, is often worst at n ight, and can be burning, aching, shooting, or lancinating. • These sx begin in the feet and may slowly ascend over months to years. Sx i n the hands do not genera l ly occur until sx i n the lower extrem ities have reached the level of the knees. I n more severe cases, the sx can spread to the trunk and head . • Neurologic exam ination reveals early loss of smal l-fi ber modal ities resulting i n ! pin prick and temperatu re sensation with later involvement of large-fi ber modal ities leading to a reduction in vibratory and proprioceptive sensation. Ankle reflexes are usually ! or absent, and more proxi mal reflexes may also become i nvolved as the neuropathy progresses. Strength is usually nl, but there can be some motor involvement leading to mild weakness and atrophy, which are usually l i m ited to intrinsic foot m uscles and ankle dorsiflexors. • Autonomic neuropathy • Gl sx are common and can include early satiety, bloating, vom iting, constipation, or diarrhea . • Cardiovascular compl ications incl ude cardiac arrhythmias and postural hypotension. • Pts may a lso have sx related to dysfunction of the G U (erectile dysfunction and incontinence) or thermoregulatory (excessive or ! sweati ng, i ntolerance of cold or heat) systems. • Regional diabetic polyneuropathy • The most common presentation is diabetic lum bosacral radiculoplexus neuropathy, which is also known as diabetic amyotrophy or Bruns-Carland syndrome. Pts usually report acute or subacute onset of severe pain i nvolvi ng the lower back, hip, and th igh . • Weakness and atrophy of the affected leg progress over the course of days to weeks, often predominantly in the anterior thigh . • Focal diabetic neuropathy • Diabetic pts are at l risk for common l i m b mononeuropath ies, particularly median neuropathy at the wrist and ulnar neuropathy at the el bow, but other nerves (femora l , sciatic, or peroneal) may be involved as wel l . Treatment

• Topical agents: Lidocaine 5% patch can be applied to pai nful areas for 1 2 hr a day. • Anticonvulsants: gabapentin ( 1 00- 1 2 00 mg tid) and pregaba l i n (50- 1 00 mg tid) • Antidepressants: amitri ptyl ine ( 1 0- 1 00 mg qhs), nortriptyline (25- 1 50 mg qhs), and d uloxetine (60- 1 20 mg dai ly) b Charcot- Marie-Tooth Disease (CMT)

Heterogeneous group of noni nflam matory inherited peri pheral neuropath ies charac­ terized by chronic motor and sensory polyneuropathy. It is the most common inher­ ited neuromuscular disorder. Transmission may be autosomal domi nant, a utosomal recessive, or X-l inked , with some sporadic cases reported. Diagnosis

• Sym metric, slowly progressive d istal motor neuropathy resulting in weakness and atrophy i n legs , often progresses to i nvolve hands • H igh-arched feet (pes cavus), claw toe deformities, and hammer toes • Atrophy of the lower legs producing a storkl ike appearance (muscle wasting does not involve the upper legs) • ! Proprioception and weakness of ankle dorsiflexors often i nterfere with balance and gait (steppage gait) Treatment

• Sym ptomatic and supportive care is managed by a m u ltidiscipli nary team including physical and occupational Rx.

333

•

•

Musculoskeletal pai n may respond to acetaminophen or NSAI Ds; neuropath ic pai n may respond to tricyclic antidepressants or drugs such as carbamazepine or gabapenti n . Occasionally, orthopedic surgery is required t o correct severe pes cavus deformity or h i p dysplasia. c Guillain-Barre Syndrome (GBS}

Acute i nflammatory demyeli nating polyradiculopathy predominantly affecting motor fu nction. GBS is the most common cause of acute ascending flaccid paralysis. Etiology •

Most pts give h/o respi ratory (mycoplasma)/G I i l l n ess (Campylobacter jejuni) with in 30 days of neurologic sx onset.

Diagnosis History • • • • •

Rapid progression of acute symmetric progressive weakness, usually > distally than proximally and > in the legs than i n the arms The pt often reports difficu lty i n ambulati ng, getting up from a chair, or c l i mbing stai rs . T h e ascending paralysis affects motor nerves more than sensory nerves. Sensory loss (predomi nantly position and vibration senses) is variable but usually m i l d . In s o m e pts, t h e i n itial manifestations m a y i nvolve t h e cranial musculature or the UEs (e.g. , ti ngl i ng of the hands) . As a genera l rule, weakness reaches its max with in 1 4 days.

Physical Exam • •

•

• •

•

•

Sym metric weakness, i n itially i nvolving proxi mal m uscles, subsequently both proxi mal and d istal m uscles l Or absent reflexes bilaterally early in the disease M i n i m u m to moderate glove and stocking anesthesia Ataxia and pain i n a segmental distribution possi ble in some pts (caused by involvement of posterior nerve roots) Autonomic abnl ities (bradycard ia or tachycardia, hypotension or HTN) also possible Respi ratory insufficiency (caused by weakness of i ntercostal muscles) Facial paresis, d ifficulty swal lowing (secondary to cranial nerve involvement)

Labs •

LP: Typical findi ngs incl ude l CSF protei n (especially lgG) and presence of few mononuclear leukocytes (albuminocytologic dissociation) .

E M G/NCS •

Slowed conduction velocities; motor, sensory, and F wave latencies. EMG may be nl i n fi rst 7 to 1 0 days .

Treatment •

• •

•

•

•

•

• •

334

•

Close mon itoring of respi ratory function (frequent [q 1 h i n itially[ bedside measurements of FVC and (-) inspiratory force to assess pulmonary muscle strength) because respi ratory fai l u re is the major potential problem in G B S . Infusion o f I V I G (0.4 g/kg/day for 5 days) . Always check serum lgA levels before infusion to prevent anaphylaxis in deficient pts. Plasma exchange : 200 to 250 m Ukg during five sessions qod IVIG and plasma exchange are equally effective . The selection of one or the other is determined by availabil ity and risk of particular com pl ications. For example, plasma exchange should be avoided in pts w/promi nent autonomic dysfu nction . There is no proven benefit o f combining IVIG a n d plasma exchange. Ventilatory support may be necessary in 1 Oo/o to 20o/o of pts. Adequate fl uid/ electrolyte support and n utrition are necessary , especially in pts w/dysautonomia or bulbar dysfunction. Aggressive nursing care is req u i red to prevent decubitus u lcers, infections, fecal i m pactions, and pressure nerve palsies and for mouth care to prevent ventilator­ associated pneumonias. Mon itor and treat a utonomic dysfunction (bradyarrhythmias or tachyarrhyth m ias, orthostatic hypotension, systemic HTN , altered sweati ng) . Treat back pain and dysesthesia w/low-dose tricyclic antidepressants, gabapenti n , a n d t h e l i ke . Opiate narcotics c a n b e used cautiously i n t h e short term b u t may compound dysautonomia. DVT prophylaxis d Chronic I nflammatory Demyelinating Polyneuropathy (CIDP}

Symmetric proxi mal and distal weakness with associated sensory loss along with l or absent reflexes for >2 mo

Diagnosis •

NCS: features of demyeli nation including prolonged distal latencies and F-waves, slowed velocities, and at least one nerve demonstrating partial conduction block (featu re of acquired demyel i nation)

H&P • •

Characterized by occurrence of symmetric weakness in both proximal and distal m uscles that progressively i over 2 mo Associated with i mpaired sensation, postural instabil ity, ! or absent DTRs, and variable cran iofacial-bulbar i nvolvement

Labs •

CSF analysis to assess for a l b u m i n-cytologic d issociation ( i . e . , i prote i n with n l c e l l count) . along with appropriate laboratory stud ies t o exclude associated conditions

Treatment • •

IVI G , plasmapheresis/plasma exchange, and corticosteroids. There is no d ifference in efficacy among these th ree modalities of Rx. Azathioprine, mycophenolate mofeti l , cyclophosphamide, rituxi mab, and cyclospori ne may be used as secondary agents .

J. AMYOTROPHIC LATERAL SCLEROSIS

(ALS) Progressive, degenerative neuromuscular condition of u ndetermined etiology affect­ ing corticospinal tracts and anterior horn cells and resulting in dysfunction of both U M N and LM N , respectively Etiology •

•

90% to 95% sporadic Of the familial cases, 1 0% to 2 0% associated w/genetic defect i n copper-zinc superoxide dism utase enzyme

Diagnosis •

•

EMG and NCS (EI Escorial criteria) Assessment of respi ratory fu nction (forced vital capacity [ FVC ] . [-] inspiratory force)

H&.P • • •

•

•

•

LM N signs: weakness, hypotonia, wasti ng, fasciculations, hyporeflexia or areflexia U M N signs: loss of fi ne motor dexterity, spasticity, extensor plantar responses, hyperreflexia, clonus Preservation of extraocular movements, sensation, bowel and bladder function Dysarthria, dysphagia, pseudobulbar affect, frontal lobe dysfunction Respi ratory i nsufficiency, typically late in the disease ALS comprises approxi mately 90% of adult-onset motor neuron diseases. Other presentations of motor neuron disease i ncl ude progressive muscular atrophy, primary lateral sclerosis, progressive bulbar palsy, progressive pseudobulbar palsy, and ALS-parki nsonism-dementia complex.

Labs •

•

•

•

Vitamin B 1 2 . thyroid fu nction , parathyroid hormone, H IV may be considered . Serum protein and i m m u nofixation electrophoresis DNA studies for SMA or bulbospinal atrophy, hexosam i n idase levels i n pure LM N syndrome 24-hour urine for heavy metals if indicated

Imaging •

•

M R I to r/o brain and spinal cord disorders Modified barium swallow to eval uate aspiration risk

Treatment • •

•

•

•

•

PEG tube placement improves n utritional i ntake, promotes weight stabil ization, and eases medication administration. N utrition, speech Rx, physical and occupational Rx services are indicated. Suction device is used for sialorrhea . Comm u n i cation may be eased with computerized assistive devices. Early discussion should cover l iving wi l l , resuscitation orders, desire for PEG and tracheostomy, potential long-term care options. Encourage contact with local support groups.

335

• • •

Ril uzole, a glutamate antagon ist, is the only FDA-approved medication known to extend tracheostomy-free survival i n pts with ALS . Spasticity may be treated pharmacologically with baclofe n , tizanidine, clonazepa m . Pseudobulbar affect m a y improve with am itriptyl ine, sertraline, o r dextromethorphan/quinine.

Disposition •

•

Mean d u ration of sx is 3 to 5 yr. Approximately 20o/o of pts survive >5 yr.

K. NEUROMUSCULAR JUNCTION

DISORDERS 0 MYASTHENIA GRAVIS (MC) Acqu i red autoimmune disorder of neuromuscular transm ission characterized by the presence of a y-globul i n Ab (ACh R-Ab) d i rected agai nst postsynaptic acetylcholine receptor or against muscle-specific tyrosine kinase ( M u S K) receptors Diagnosis H&P • •

•

• •

•

•

•

The hall mark of MG is weakness made worse w/exercise and improved by rest. Sx fl uctuate and are often better in the morni ng. >50o/o of pts present i n itially w/ptosis, ocular muscle weakness, or both . Pts have difficu lty i n chewi ng, abnl smile, dysarth ria, dysphagia. I nvolvement of the respi ratory m uscles may requ i re i ntubation and assisted ventilatio n . Pain m a y occur i n fatigued m uscles (e.g. , neck m uscles) . Clinical man ifestations reproducible w/exercise . Observation of the pt perform ing repetitive m uscle contractions of involved m uscles will demonstrate rapidly developing weakness . PE may be nl at rest. Pts w/h/o ptosis wi l l demonstrate fatigue weakness and ptosis when asked to sustai n upward gaze for >3 m i n w/o i nterruption .

Labs and Other Tests • •

•

•

• •

•

Edrophonium test: improvement of sx after use of anticholinesterase med ications (edrophonium) EMG: si ngle-fiber electromyography: sensitivity >90 o/o but nonspecific MRI or CT of anterior mediastin u m : thymoma found i n 1 2o/o TS H : thyroid disease found i n 30o/o of pts Vitamin B 1 2 leve l : r/o pernicious anemia ANA, RF ( association w/S LE, RAJ (+ ) Ab against M u S K receptors

Treatment • • •

•

Acetylcholinesterase i n h ibitors: Pyridostigmine is fi rst-line Rx. I m m unosuppressants: corticosteroids, azath iopri ne, mycophenolate mofetil, rituximab for more severe or general ized disease Plasmapheresis and IVIG in refractory cases Thymectomy in thymomatous MG

D LAMBERT-EATON MYASTH ENIC SYN DROME

Disorder of neuromuscular transmission caused by Ab aga inst presynaptic voltage­ gated P/0 Ca channels on motor and autonomic nerve terminals. The two forms are paraneoplastic (most common, small cell lung cancer 50-70°/o) and non paraneoplastic (autoi mmune).

Diagnosis H&P •

• • •

Weakness w/! or absent muscle stretch reflexes Proximal LE m uscles affected most Transient strength improvement w/brief exercise Autonomic dysfunction common (dry mouth in 75o/o, sexual dysfu nction, blurred vision, constipation, orthostasis)

EMG/NCS

336

•

•

! Motor ampl itudes w/nl sensory studies Labs: T titers of P/0-type calci u m channel Ab

Treatment • •

Acute : plasma exchange (200-250 m Ukg over 1 0- 1 4 days) or IVIG (2 g/kg over 2-5 days) Chronic Rx: antichol inesterase agents (pyridostigmine )

L. HEAD INJURY 0 EPIDURAL H EMATOMA

Col l ection of blood between the sku l l and dura mater (Fig. 1 0-5)

FIGURE 1 0-5. Epidural hematoma. The arrows show the pattern of brain displacement. (From Weissleder R, Wittenberg J, Harisinghani M, Chen JW [eds]: Primer of Diagnostic Imaging, 5th ed. St. Louis, Mosby, 201 1 .)

Etiology • •

Head trauma causing tempora l bone fracture resulting i n middle meningeal artery tear Neoplasms that have spread i nto the epidural space

Diagnosis H&P •

• •

Lucid i nterval after the head trauma is followed by progressive red uction in the level of consciousness as the hematoma enlarges and the underlying brain is displaced i nward . The i n itial i njury causes brain concussion and loss of consciousness from which the pt awakens and may have some headache but seems otherwise to have recovered. Downward transtentorial hern iation may develop rapidly, causing third nerve compression and an ipsilateral hemiparesis.

Imaging •

Bra i n CT

Treatment •

Emergency surgical evacuation

IDI SUBDURAL H EMATOMA

Bleeding i nto the subdural space, caused by rupture of bridging veins between the bra i n and venous sinuses (especially where stretched by underlying cerebral atrophy) . Figure 1 0-6 illustrates subdural hematoma and com pares it with epidural hematoma .

Diagnosis H&P •

•

•

•

•

Vague headache, often worse in morning than evening Some apathy, confusion , and clouding of consciousness is common, although frank coma may compl icate late cases. Chronic subdural hematomas may cause a dementia picture . Neurologic s x m a y b e transient, sim ulating TIA. Almost any sign of cortical dysfunction may occur, including hemiparesis, sensory deficits , and language abnl ities, depending on which part of the cortex is compressed by the hematoma. New-onset seizures should raise the i ndex of suspicion .

337

Epidural hematoma

Subdural hematoma

I ncidence Cause Location

I n 5 m i n ; PTA >24 h Any LOC

AAN, American Academy o f Neurology; LOC, l o s s of consciousness; PTA, posttraumatic amnesia.

Modified from Vincent JL, Abraham E, Moore FA, et al [eds) : Textbook of Critical Care, 6th ed. Philadelphia, Saunders, 2 0 1 1 .

•

When used i n combi nation, symptom assessment, balance assessment, and neurocognitive testing provide a sensitivity of >90o/o for the identification of concussion.

Imaging •

Head CT or M R I for grade I I or I l l concussion with persistent abn l ities on exam or sym ptoms lasting > 1 wk

Treatment •

• •

Immed iate removal of ath lete from game/ath letic activity Physical rest: no return to play until asym ptomatic for atleast 24 hours Cognitive rest to l i m it sx • Modifications at school • Modifications at home/recreation • Sleep encouraged

339

11

Pulmonary and Critical Care

A. CHEST X-RAY 0 EVALUATING THE CH EST X-RAY

•

Figure 1 1 - 1 i l l ustrates the location of various pulmonary and cardiac structures seen on a CXR (PA view) . The fol lowing is a short guide to reading a CXR. 1 . Check exposure tec h n ique for l ightness or darkness. 2. Verify left and right by looking at the heart shape and stomach bubble, respectively. 3. Check for rotation . Does the thoracic spine shadow al ign i n the center of the stern u m between the clavicles? 4 . Make sure the CXR is taken i n fu ll inspiration ( 1 0 posterior or 6 anterior ribs should be visible) . 5 . Is the fil m a portable, AP, or PA film? (The heart size cannot be accurately judged from an AP fi l m . ) 6 . Check t h e soft tissues for foreign bodies or SC emphysema. 7. Check all visible bones and joi nts for osteoporosis, old fxs, metastatic lesions, rib notchi ng, or presence of cervical ribs. 8 . Look at the diaphragm for tenting, free a i r, and position. 9 . Check h i lar and mediastinal areas for the fol lowing: size and shape of the aorta, presence of hilar nodes, promi nence of hilar blood vessels, elevation of vessels (left sl ightly h igher) , and elevation of the left main stem bronchus indicati ng left atrial enlargement. 1 0 . Look at the heart for size, shape, calcified valves, and enlarged atria . 1 1 . Check t h e costophrenic angles for fluid or pleura l sca rri ng. 1 2 . Check the pulmonary parenchyma for infiltrates, l i nterstitial markings, masses, absence of nl margi ns, air bronchograms, or l vascularity and "silhouette" signs. 1 3 . Look at the lateral fil m for the following: confirmation and position of q uestionable masses or i nfi ltrates, size of retrosternal air space, AP chest diameter, vertebral bodies for bony lesions or overlying i nfi ltrates, and posterior costophrenic angle for small effusion.

D CALCIFICATIONS ON CHEST X-RAY •

• • • •

•

•

•

Lung neoplasm (primary or metastatic) Sil icosis Idiopath ic pulmonary fi brosis (I PF) Tuberculosis H i stoplasmosis Dissemi nated varicella infection M itral stenosis (end-stage) Secondary hyperparathyroidism

0 CARDIAC ENLARG EMENT Cardiac Chamber Enlargement

• •

•

• • • • • • •

•

340

•

•

•

•

Chronic volume overload M itral or aortic regurgitation Left-to-right shunt (PDA, VS D, AV fistula) Cardiomyopathy Ischemic Nonischemic Decompensated pressure overload AS HTN H igh-output states Severe anemia Thyrotoxicosis Bradycardia Severe sinus bradycardia Complete heart block

Trachea Cari na Aortic knob Azygos vei n -----= Right mai n ----= pulmonary artery Left atri u m

----=

Right atri u m

_ __ __,

Breast shadow

.....-r:"'"

Liver

Main pulmonary artery Descending thoracic aorta Left ventricle Right ventricle

---··-.- Left costophrenic angle

Raised hu merus Trachea Ascending aorta Retrosternal air space Right ventricle

""------7- Scapular blades Right pulmonary

_::.=__.... --�- artery

Left atri um Left ventricle I nfe rior vena cava Posterior costophrenic angle

FIGURE 1 1 - 1 . Normal anatomy on the female chest radiograph in the upright posteroanterior projection (A) and in the lateral projection (B). (From Mettler FA: Primary Care Radiology. Philadelphia, Saunders, 2000.)

Left Atrium •

•

•

LV fai l u re of any cause M itral valve d isease Myxoma

Right Ventricle •

• • • • • • • • •

Chronic LV fai l u re of any cause Chronic vol ume overload Tricuspid or pulmonic regurgitation Left-to-right shunt (AS D) Decompensated pressure overload Pulmonic stenosis Pulmonary HTN Primary Secondary (PE, COPD) Pulmonary vena-occlusive disease

Right Atrium • • • •

RV fai l u re of any cause Tricuspid valve disease Myxoma Ebste i n ' s anomaly

341

Multichamber Enlargement • •

•

Hypertrophic cardiomyopathy Acromegaly Severe obesity

Pericardial Disease •

• •

Pericardia I effusion w/ or w/o tamponade Effusive constrictive disease Pericardia! cyst, loculated effusion

Pseudocardiomegaly •

•

•

•

Epicardial fat Chest wal l deformity (pectus excavatu m , straight back syndrome) Low l u ng vol umes AP CXR

0 CAVITARY LESION ON CHEST X-RAY

Necrotizing Infections Bacteria : a n a e robes, Staphylococcus aureus, enteric gra m (-) bacte r i a , Pseudomonas aeruginosa, Legionella spec i e s , Haemophilus influenzae, Streptococcus pyogenes, Streptococcus pneumoniae, Rhodococcus, Actinomyces • Mycobacteria : Mycobacterium tuberculosis, Mycobacterium kansasii, Mycobacterium avium-intracellulare • Bacteria-like: Nocardia species • Fu ngi : Coccidioides immitis, Histoplasma capsulatum, Blastomyces hominis, Aspergillus species, Mucor species • Parasitic : Entamoeba histolytica, Echinococcus, Paragonimus westermani •

Cavitary I nfarction •

•

Bland infarction (w/ or w/o superim posed i nfection) Lung contusion

Septic Embolism Staphylococcus aureus

• • •

Anaerobes Others

Vasculitis •

•

Wegener's gra n u lomatosis Periarteritis

Neoplasms • •

•

Bronchogenic carci noma Metastatic carcinoma Lym phoma

Miscellaneous Lesions •

•

•

•

Cysts, blebs, bullae, or pneumatocele w/ or w/o fluid collections Sequestration Empyema w/ai r-fl uid level Bronchiectasis

0 MEDIASTINAL MASSES OR WIDENING ON CHEST X-RAY •

• • •

• •

• •

• •

•

342

• •

•

Lymphoma: Hodgki n ' s disease and non-Hodgki n ' s lymphoma Sarcoidosis Vascular: aortic aneurysm , ectasia or tortuosity of aorta or bronchocephalic vessels Carcinoma: l u ngs, esophagus Esophageal diverticula H iatal hernia Achalasia Prominent pul monary outflow tract: pul monary HTN , PE, right-to-left shu nts Trauma: mediastinal hemorrhage Pneumomed iasti num Lymphadenopathy caused by sil icosis and other pneumoconioses Leukemias Infections: TB, viral (rare). mycoplasmal (rare), fu nga l , tularemia Substernal thyroid

• •

•

•

•

Thymoma Teratoma Bronchogenic cyst Pericardia! cyst Neurofibroma, neurosarcoma, gangl ioneuroma

B. USE AND INTERPRETATION OF

PULMONARY FUNCTION TESTS • •

•

Basic spi rometry: Figure 1 1 -2 PFTs in common l ung diseases: Table 1 1 - 1 Flow vol u m e curves : Figure 1 1 -3

�

,"·� Total lung capacity

I nspiratory capacity

4

3

+

t

2

t

---1-- � 1 � � : --Expi ratory rese e volume

Functional residual capacity

- -

Ro 0

1

1 m

-

Basic spirometry. Long volumes obtained with a bell spirometer. (From Kiss GT- Diagnosis and Management of Pulmonary Disease in Primary Practice. Menlo Park, Calif, Addison- Wesley, 1 982.) FIGURE 1 1 -2 .

TABLE 1 1 - 1 • Pulmonary Function Test Patterns in Common Lung Diseases Parameter

Disorder

FVC

Diffusion (DLco)

Nl, i Nl, i

TLC Nl, i Nl, i

!

Nl, i

Nl, i

Nl

FEV1

FEV1/FVC

Asthma

!

!

!

Chronic obstructive bronchitis Chronic obstructive bronchitis w/ bronchospasm Emphysema

!

!

!

!

!

RV

Nl

+

Nl

!

!

!

I nterstitial fibrosis

!

Nl, !

Nl, i

Nl, i Nl, !

Nl, i !

Nl, ! !

Obesity, kyphosis

!

Nl, !

Nl, i

Nl, i

!

Nl

l, greater than predicted; l, less than predicted.

Bronchodilator Response

+

343

Normal

Early small Chronic airway obstructive obstruction disease

Variable Fixed large extrathoracic Restrictive ai rway large ai rway disease obstruction obstruction

Variable intrathoracic obstruction

50 1 00 0 Volume (% FVC)

Flow-volume curves of restrictive disease and various types of obstructive diseases compared with normal curves.

FIGURE 1 1 - 3 .

C . PULMONARY FORMULAS •

•

•

Lung vol umes: Box 1 1 - 1 Alveolar-arterial 02 grad ient (A-a gradient) : Box 1 1 -2 Eval uation of pt in respi ratory fa ilure : Box 1 1 -3

Box l l·l • lung Volumes: Normal Volumes ht lJpright Subjeets Volume or Capacity Approximate Value in Upright Subjects Total lung capacity (T1C)

Vital capacity (VC) Residual volume (RV)

61 4.5 1 1.5 1

Inspiratory capacity (I C)

31

Functional residual capacity (FRC)

31

Inspiratory reserve volume (IRV) Expiratory reserve volume (ERV)

2.5 1 1.5 1

Tidal volume (Vr) The VC is calculated as:

0.5 1

VC = I RV + ERV + Vr

The RV is calculated as the difference between the FRC and the ERV:

RV = FRC - ERV Alternatively, if the T1C and VC are known, the following formula can be used:

RV = TLC - VC

( :�� )]

Box l l-2 • Alveolar-Arterial Oxygen Gradient (A·a Gradient)

A - a gra d ie n t =

[

7 1 3 (FI02 ) -

P

2

- P a02

Normal A-a gradient = 5-15 mm Fl02, fraction of inspired oxygen (normal = 0.21-1.0) PaC02, arterial carbon dioxide tension (normal = 35-45 mm Hg) Pa02, arterial partial pressure of oxygen (normal = 70-100 mm Hg) Ddx of A-a gradient:

Abnormality

344

1 5 % 02

100% 02

Diffusion defect

Increased gradient

Correction of gradient

V/Q mismatch

Increased gradient

Right-to-left shunt (intra­ cardiac or pulmonary)

Increased gradient

Partial or complete correction of gradient Increased gradient (no correction)

Box l l-3 • Formulas for Evaluation of Patients in Respiratory Fallure

Age-predicted Paoz Expected Paoz - 0.3(age - 25) [expected Paoz at sea level is 100 mg/Hg] As a rough rule of thumb: Expected Paaz ::::: Floz (%) x 5 AaDOz = (Fioz x [BP*- 47]) - (Paoz + Pacoz), where BP = barometric pressure Paoz/Fioz ratio =

Oxygenation i nd ex = [ ( m e a n a i rway pressure x F I 0 2 )/Pao2 ]

VoNr = ( Paco2 - P Eco 2 ) /Paco2 ( N = 0 . 2 - 0 . 4)

x

1 00

Prom Vincent JL, Abraham E, Moore FA, et al (eds): Textbook of Critical Ca1·e, 6th ed. Philadelphia, Saunde?·s, 201 1 .

AaD02, Alveolar-arterial gradient; Vn, dead space.

D. MECHANICAL VENTILATION INDICATIONS (Please see section " M " fo r Respiratory Failure Classification)

1 . Clin ical assessment: presence of apnea, tachypnea (>40 bpm), or respi ratory fai l u re that cannot be adequately corrected by any other means 2. Clin ical instabil ity, fa il ure to protect the a i rway-usually from dec l i n i ng mental status 3 . ABGs: severe hypoxemia despite high-flow 0 2 or sign ificant C0 2 retention (e.g. , Po2 50) 4. Physiologic parameters are of l i m ited use because many pts w/respi ratory insufficiency are unable to perform PFTs, and their respi ratory fai l u re mandates immediate i ntervention. Some of the commonly accepted physiologic parameters for i ntubation and respi ratory support are as fol l ows: a. VC 1 05 Note: The c l i n ical assessment is the most i m portant determ inant of the need for mechanical venti lation because neither physiologic parameters nor ABGs distinguish between acute and chronic respi ratory insufficiency (e.g. , a Pco 2 >60 mm Hg and an RR >30/m i n may be the " norm " for a pt w/COPD, whereas the same values i n a young, otherwise healthy adult are ind ications for intubation and mechanical venti lation) .

ICU SEDATION Commonly used agents are GABA agonists such as propofol and benzos. These agents can cause respi ratory depression and deliri u m . The a-adrenoreceptor agonist dexme­ detomidine is as effective for sedation but sign ificantly better i n pts at risk for deliri u m .

COMMON MODES OF MECHANICAL VENTILATION Invasive mechanical ventilation is defi ned as ventilatory support supplied through en­

dotracheal i ntubation. The use of devices that apply interm ittent (-) extrathoracic pressure or furnish interm ittent positive pressure th rough a tight-fitting nasal or face mask w/o an artificial a i rway in place is known as noninvasive ventilation. The del ivery of gas under positive pressure i nto the airways and the l ungs is known as positive­ pressure ventilation (Table 1 1 -2) . 1 . IMV: The p t is allowed to breathe spontaneously, and the venti lator del ivers a number of mach ine breaths at a preset rate and volume. a . Advantages and indications i. I MV is indicated i n the majority of spontaneously breathing pts because it maintains respi ratory muscle tone and results i n less depression of cardiac output than with ACV. i i . It is usefu l for wean i ng because as the I MV rate is !, the pt gradually assumes the bulk of the breath ing work. b. Disadvantages i. The i work of breathing resu lts in i 02 consumption (deleterious to pts w/ 345 myocardial insufficiency). i i . I MV is not useful in pts w/depressed respi ratory drive or impaired neurologic status.

TABLE 1 1 -2 • Modes of Positive-Pressure Ventilation

Mode

Description

Advantages and Disadvantages

Controlled mechanical ventilation (CMV)

Ventilator f, i�spiratory time, and VT (and thus V E) preset

Assisted mechanical ventilation (AMV) or assistcontrol ventilation (ACV) I ntermittent mandatory ventilation ( I MV)

Ventilator VT and inspiratory time preset. but patient can f (and thus V E) Ventilator delivers preset VT, f, and inspiratory time, but patient also can breathe spontaneously

Can be used in patients w/sedation or paralysis; ventilator cannot respond to ventilatory needs Ventilator may respond to ventilatory needs; ventilator may undertrigger or overtrigger, depending on sensitivity May ! asynchronous breathing and sedation requirements; ventilator cannot respond to ventilatory needs Same as I MV, and patient not overi nflated by receiving spontaneous and ventilator breaths at same time May reduce peak airway pressure; may cause auto-PEEP i comfort and ! work of breathing; ventilator cannot respond to ventilatory needs Peak inspiratory pressures may be ! ; hypoventilation may occur

Synchronized intermittent mandatory venti lation (SI MV) H igh-frequency ventilation ( H FV) Pressure support ventilation (PSV)

Same as I MV, but ventilator breaths delivered only after patient finishes inspiration Ventilator f is and VT may be smaller than Vo Patient breathes at own f; VT determined by inspiratory pressure and CRs

Pressure control ventilation (PCV) I nverse ratio ventilation (I RV)

Ventilator peak pressure , f, and respiratory time preset I nspiratory time exceeds expiratory time to facilitate inspiration

Airway pressure release ventilation (APRV)

Patient receives C PAP at h igh and low levels to simulate VT

Proportional assist ventilation (PAV)

Patient determines own f, VT, pressures, and flows

May improve gas exchange by i time spent on inspiration; may cause auto-PEEP May improve oxygenation at lower airway pressure; hypoventilation may occur May amplify spontaneous breathing; depends entirely on patient's respiratory drive

Modified from Goldman L, Schafer AI (eds) : Goldman's Cecil Medicine, 22nd ed. Philadelphia, Saunders, 2004.

CRs, Respiratory system compliance; f, respiratory rate; Vo, dead space.

i i i . It was previously assumed that the degree of respi ratory m uscle rest was proportional to the level of machine assistance. However, more recent evidence ind icates that respi ratory-sensor output does not adjust to breath­ to-breath changes in respi ratory load , and I MV may therefore contribute to the development of respi ratory muscle fatigue or prevent recovery from it. 2. ACV: The pt breathes at his or her own rate, and the ventilator senses the inspiratory effort and del ivers a preset Vr w/each pt effort; if the pt's RR .J. past a preset rate , the ventilator del ivers tidal breaths at the preset rate. a. Advantages and indications: ACV is useful i n pts w/neuromuscular weakness or CNS disturbances. b . Disadvantages i. Tachypnea may result in sign ificant hypocapnia and respiratory alkalosis. ii. I m proper setting of sensitivity to the (-) pressure necessary to trigger the ventilator may result in "fighting the ventilator" when the sensitivity is set too low. i i i . l Sensitivity may result i n hyperventilation; sensitivity is generally set so that an inspiratory effort of 2 to 3 em will trigger venti lation. iv. The respi ratory m uscle tone is not well maintained i n pts on ACV, and this may result in d ifficulty w/wean i ng. 3 . CMV: The pt does not breathe spontaneously; the RR is determined by the physician ; the venti lator assumes all respiratory work by delivering a preset volume of gas at a preset rate. a . Advantages and indications i. CMV is useful i n pts who are unable to make an inspiratory effort (e.g. , severe CNS dysfunction) and in pts w/excessive agitation or breath i ng effort. ii. Pts w/excessive agitation are often sedated w/morphine or benzos and paralyzed w/pancuronium bromide; adequate sedation is necessary to elimi nate awareness of paralysis. iii. I n itial pancuron i u m dose is 0 . 08 mg/kg IV i n adults. 346 iv. Later incremental doses starting at 0 . 0 1 mg/kg may be used as necessary to mai ntain paralysis; pancuron i u m should be adm i n istered only by or under

the supervision of experienced clin icians; a combination of neostigm ine and atropine may be used to reverse the action of the pancuro n i u m . b . Disadvantages: Paralyzed pts on C M V must be closely mon itored because venti lator malfunction or disconnection is rapidly fatal . 4. SIMV: A hybrid o f ACV a n d I MV, t h e ventilator del ivers a n umber o f specified breaths/m i n (as w/I MV) . However, at the appropriate i nterval (e.g. , q6sec if machine rate is 1 0 breaths/m i n ) , the machine waits for an En pressure deflection to signal pt effort and then del ivers a positive-pressure breath ; ventilator breaths are thus synchron ized w/pt respi ratory efforts , as w/assist featu res of ACV. 5. Other useful ventilation modes are as follows: a . Pressure control ventilation (PCV): A venti latory mode i n which inspi ratory pressure , RR, and inspiratory time (T1) are determ ined by the ventilator setti ngs. Because i nspiratory pressure is the controlled variable, Vr during PCV is infl uenced by the mechanical properties of the respi ratory system (resistance and compliance). b. Pressure support ventilation (PSV): A venti latory mode i n which the pt's inspiratory effort is supported by a set level of inspiratory pressure. This pressure is maintained until respi ratory flow falls below a threshold value, signal i ng the onset of expiration. Vr during PSV is determ ined by pt effort and the mechanical properties of the l ung. PSV differs from PCV i n that the RR and the T1 are determ ined by the pt. c. Inverse ratio ventilation (IRV): A venti latory strategy i n which the inspiratory­ to-expi ratory ratio is prolonged to 1 : 1 or greater. I n pts w/ARDS, I RV is used to improve oxygenation by i ncreasing mean airway pressure . This modal ity is used as a salvage Rx when adequate oxygenation can not be achieved w/ conventional venti lation in ARDS . When used , pressure cycled I RV is preferred because of l barotrauma risk. d. Noninvasive positive-pressure ventilation (NPPV), Continuos positive airway pressure (CPAP), Bi-level positive airway pressure (BiPAP): In N P PV, ventilatory support is del ivered by use of a mechanical ventilator connected to a mouthpiece or mask instead of an En. It is very useful in pts w/chronic respi ratory failure caused by neuromuscular disease or thoracic deform ities and in pts w/idiopathic hypoventi lation. It improves the pt's wel l-being and may eliminate the need for tracheostomies. It is also used in pts as a short­ term bridge to avoid intubation and mechanical venti lation, when possible, in conditions that are rapidly reversible, such as hypercarbic respi ratory fail ure in COPD and, importantly, acute pul monary edema in heart failure. It is also sometimes used as salvage Rx in pts w/any of the indications for intubation who do not want to be intubated . CPAP is applied with an oxygen source connected to either a tight-fitting nasal or full-face mask or via nasal prones. It delivers high concentration of oxygen and maintains (+) airway pressure in the spontaneously breath ing patient. It offers the benefit of maintain ing alveolar expansion and decreases work of breathing. BiPAP, like CPAP can be provided by mask, but it requires a ventilator to assist with flow delivery. The patients i nspiratory effort triggers the BiPAP machine to del iver decelerating flow in order to reach a preset pressure, defined as inspiratory positive ai rway pressure. When a pt's own inspiratory flow falls below a preset amount, venti latory assistance ceases and maintains airway pressure at a predetermined value (usually 5- 1 0 mmHg) .

SELECTION OF VENTILATOR SETTI NGS

1 . Vr 1s 1 0 to 1 5 m Ukg of ideal BW. Low volume venti lation = 6-8 m l/kg w/ARDS 2. Rate (nu mber of tidal breaths del ivered per m i n ute) is 8 to 1 6 , depending on the desired Paco 2 or pH (i rate = l Paco2) . 3 . Mode is I MV, ACV, CMV (or PCV or PSV, depending on what is available at one's institution). 4. 02 concentration (F102) : The i n itial F102 should be 1 00% unless it is evident that a lower F1o2 wi l l provide adequate oxygenation. The F1o2 should be cali brated down as q uickly as possible to prevent 02 toxicity. 5. Obta i n ABGs 1 5 to 30 m i n utes after i n itiation of mechanical ventilation. 6. Immediate CXR is indicated after intubation to evaluate for correct placement of rn. 7 . Sedation orders (e.g. , morph ine, diazepam) are necessary in most pts. 8. PEEP: a . The appl ication of PEEP may prevent the closure of edematous smal l 347 a i rways; i t is indicated when arterial oxygenation is inadequate (satu ration 50%; it is useful in pts w/d iffuse l u ng edema and

TABLE 1 1 -3 • Effects of Ventilator Setting Changes Typical Effects on Blood Cases

Ventilator Setting Changes i PIP i PEEP

i Rate (I MV) i 1/E ratio

i F1o2 i Flow i Power (in H FOV)

!

i

i

i

Minimal i

! No change

j j

No change

Minimal i No change

M i nimal ! !

i PAW (in H FOV)

i

Minimal !

From Tschudy M M , Arcara KM : The Harriet Lane Handbook, 1 9th ed. Philadelphia, Mosby, 20 1 2 . HFOV, High-frequency oscillatory ventilation; /IE, inspiratory/expiratory ratio; PA W , mean airway pressure; PIP,

peak inspiratory pressure.

TABLE 1 1 -4 • Common Ventilator Machine Settings for Various Disorders

Condition

Mode

Depressed CNS drive

Mandatory ACV, S I MV

Neuromuscular i nsufficiency

Acute: mandatory ACV, S I MV Mild, recovering: S I MV and PSV, PSV alone

COPD

Early: ACV, S I MV Late: see text

Yt = 1 0 mUkg VE = 6-8 Umi n

Vt = 8- 1 o m Ukg VE = 6-8 Umi n Guarantee VT >350 m l w/PSV breaths

yt = 8 mUkg VE: minimize, usually 8- 1 0 Umin Peak fiow �60 Umin

PEEP (em H20)

Pressure Targets

0-5

Peak usually 9 0%, FI02 ::;0.6 • No infiltrates on chest radiograph (COPD, asthma, PTE), F'IC)2: start at 0.4 and adjust according to Spo2 (consider starting higher if PE is strongly suspected) 3. Ventilation • Vr: begin with 8 miJkg PBW; decrease to 6 miJkg PBW over a few hours if acute lung injury present • Rate: begin with 10-20 breaths/min (10-15 if not acidotic; 15-20 if aci�otic); adjust for pH; goal pH >7.3 with maximal rate of 35 ; may accept lower goal if V E high 4. Secondary modifications • Triggering: in spontaneous modes, adjustment of sensitivity levels to minimize effort • Inspiratory flow rate of 40-80 lJmin; higher if tachypneic with respiratory distress or if auto-PEEP present, lower if high pressure in ventilator circuit leads to a high-pressure alarm • Assessment of auto-PEEP, especially in patients with increased airways obstruction (e.g., asthma, COPD) • 1/E ratio: 1:2, either set or as function of flow rate; higher ( 1 : 3 or more) if auto-PEEP present • Flow pattern: decelerating ramp reduces peak pressure 5. Monitoring • Clinical: blood pressure, EGG, observation of ventilatory pattern including assessment of dyssynchrony, effort or work by the patient; assessment of airflow throughout expiratory cycl� • Ventilator: Vr, V E, airway pressures (including auto-PEEP), total compliance • ABGs, pulse oximetry Modified from Goldman L, Schaj!ff AI (eds): Goldman's Cecil Medicine, 24th ed. Philadelphia, Saunders, 2012. *Decisions within this algorithm will be influenced by the specific conditions of the individual patient. HFOV, high-frequency oscillatory ventilation; /IE ratio, inspiratory-to-expiratory ratio; NlV, noninvasive ventilation; PBW, predicted body weight; PTE, pulmonary thromboembolism.

MAJOR COMPLICATIONS 1 . Pulmonary barotrauma (e.g. , pneumomediastinum, pneumothorax, SC emphysema, pneumoperitoneum) is generally secondary to high levels of PEEP, excessive Vr, h igh peak airway pressures, and coexistence of significant lung disease . 2 . Pulmonary thromboemboli can be prevented by vigorous leg care, antiembolic stockings, and use of prophylactic LMW H . 3 . G l bleedi ng: Prophylaxis w/IV ranitidine 50 m g q8h, PPis, or sucralfate suspension, 1 g q6h through NG tube, is indicated in most pts on mechanical ventilators. 4. Arrhythmias: Avoid the use of arrhythmogenic drugs and prevent rapid acid-base sh ifts . 5. Accumulation of large amount of secretions: Frequent respi ratory toi l et is necessary in all pts on mechanical ventilators. Consider mouth care with ch lorhexidine. 6. Others i nclude nosocomial i nfections, laryngotracheal injury, malnutrition, hypophosphatemia, 02 toxicity, and psychosis. Risk factors for pneumonia are severe i l l ness, old age (>60 years) , prior administration of abx, and supine head 349 position . Respiratory ICU pts who are managed in the sem i recumbent (30- to 45-degree head-up) position have a lower incidence of nosocomial pneumon i a . U s e o f sucralfate rather t h a n H2 antagonists is also associated w/lower incidence

of nosocomial pneumon ia. Extubation as rapidly as possi ble is i m portant to help prevent venti lator-associated pneumonia.

WITH DRAWAL OF MECHANICAL VENTILATORY SUPPORT Common Criteria for Ventilator Weaning

1 . I m proved clin ical status (the pt is alert and hemodynamically stable) ; the process that requ i red mechanical ventilation is reversed . 2 . Adeq uate oxygenation (Pao 2 >60 mm Hg w/i nspired 0 2 concentration of 40%) 3. pH 7 . 33 to 7 . 48 w/acceptable Paco 2 4. RR :525 breaths/m i n 5 . V C 2= 1 0 m Ukg 6. Resting V E < 1 0 Um i n , w/abil ity to double the resting V E 7 . Peak pressure more (-) than -25 em H 20 8. Vr >5 m Ukg 9. The ratio of respi ratory frequency to VT during 1 m i n ute of spontaneous breathi ng, also known as the rapid shallow breathing index (f!Vt}, is a good predictor of a pt's readiness for weaning; a value of < 1 00 breaths/m in/L indicates that wea n i ng probably will be successfu l , especially if it is confirmed by serial measurements. Note: The preced ing criteria are only guidel ines; sign ificant variation may be pres­ ent (e.g. , an RR of 30 breaths/m i n may be acceptable i n a pt w/COPD) . Fai l u re to meet these criteria does not mean that the pt will not be weaned successfu l ly. Figure 1 1 -4 is an algorithm for disconti n u i ng venti lation and for extubation.

APPROACH TO DISCONTIN UING VENTI LATION/EXTUBATION 1 . Daily assessment: Is patient ready for a spontaneous breathing trial? • General: resolving process, patient alert, no continuous sedation • Gas exchange: P/F >200; F1o 2�0% • Hemodynamics: no vasopressors • Respiratory: PEE P$5-7 em H2 0

Evaluate and treat reversible causes of failure • Sedation, fluid status, myocardial ischemia, pain control, bronchodilator need, etc.

Yes

-t

2. I nitiate screening for spontaneous breathing trial (SBT) : • Monitor patient with EGG, oximetry • Patient breathes spontaneously on T-piece, or on PSV of 5-7 em H20 • Monitor physiologic variables (RR, gas exchange, hemodynamics, subjective comfort)

�

If patient ph siologically stable, continue

If patient physiologically unstable

Rei nstitute ventilation Stable, nonfatiguing, comfortable

•

Failed criterion

!

3. Continue SBT for 30- 1 20 min utes: Discontinue if any of the fol lowing occurs: • General : t anxiety or sweating • Gas exchange: Spo 2 1 0 mm Hg • Hemodynamics: sustained HR changes of > ± 20% OR HR > 1 40/min; SBP 1 80 mm Hg • Respi ratory: RR > 35/min for >5 min; signs of . . r WOB (paradOXIcal breathing, accessory muscles . . . ) No failure criterion met

I

Reintubate

I

I

Failure

4. Extubate FICURE 1 1 -4. Algorithm for assessing whether a patient is ready to be liberated from mechanical ventilation and extubated. PIF, Paoz!F!oz ratio; WOE, work of breathing. (Prom Goldman L, Schafer AI [edsj: Goldman's Cecil Medicine, 24th ed. Phil.adelphia, Saunders, 2012.)

Methods of Weaning

350

1 . Wea n i ng by I MV a. G radually L the I MV as tolerated (e.g. , two breaths q3-4h ) , mon itoring ABGs PRN . Mon itoring of c l i n ical signs (RR, pt' s comfort, and Vr) is usually sufficient to avoid repeated ABGs.

2. 3.

4.

5.

b . Do not change more than one parameter at a time. c . When the pt is tolerati ng an I MV of 4 to 6 , a trial wrr tube can be attempted . The T tube is attached to the ETI and del ivers humidified 02 (F1o2 40%) . d . If the pt tolerates the T tube wel l , extubation may be attem pted . i . Have adequate equipment and personnel avai lable if rei ntubation is necessary (start early i n the day) . i i . Suction airway and oropharynx. i i i . Deflate cuff and extubate . iv. Adm i n ister 02 by face mask (F1o2 40%- 1 00%) . v. Auscultate the l u ngs for adequate air movement. vi. Closely mon itor VS . vi i . Obtain ABGs approximately 1 5 to 30 m i n utes after extubation. e . Rei ntubate if extubation is poorly tolerated . Stable pts w/o pulmonary disease and w/good probabil ity of quick extubation (e.g. , after uncom plicated cardiac su rgery) may be given a d i rect trial of T tube (bypassing gradual l of I MV) . PSV a. Titrate pressure to achieve a frequency of :525 breaths/mi n ; al low a CPAP of :5cm H20. b. Set pressure support i n itially at 1 8. 0 ± 6. 1 em H 20 , and attempt to reduce this level of support by 2 to 4 em H20 at least bid. c . Extubate pts who tolerate a pressure support setting of 5 em H20 for 2 h r w/ no apparent i l l effects . I nterm ittent trials of spontaneous breathing a . Disconnect the stable pt from the ventilator and al low the pt to breathe spontaneously through either a T-tube circuit or a conti nuous-flow circuit designed to provide a CPAP of :55 em H20 . b. Attempt t h e trial a t least bid and grad ually l t h e duration o f t h e trial. c . Provide ACV for � 1 hour between the trials. d . Extubate pts who are able to breathe on their own for �2 hr w/o signs of distress. Once-daily trial of spontaneous breathing a . Disconnect the stable pt from the venti lator and allow h i m or her to breathe spontaneously th rough a T-tube circuit for :52 h r each day. b. Extubate pts who tolerate a 2-hour trial w/o signs of distress. c. Reinstitute ACV for 24 hr if signs of i ntolerance develop.

Failure to Wean from Mechanical Ventilator

Fa i l u re usually resu lts fro m p remature attem pts at wea n i ng (e.g. , pt is h e m ody­ nam ically u n stable) . Other common , revers i b l e causes of fa i l u re to wean are as fol lows : 1 . Hypophosphatemia, hypomagnesemia, hypokalemia 2 . Drug toxicity (e.g. , excessive CNS depression from analgesics, sedatives) . Contin uous i nfusions of sedative drugs may prolong the duration of mechanical venti lation. Daily i nterruption of sedative infusions until the pt is awake l the duration of mechanical venti lation. 3 . Bronchospasm 4. Excessive secretions 5. Sign ificant acid-base disturbances (e.g. , metabolic alkalosis depresses respiratory drive) 6. Hypothyroidism 7 . Malnutrition 8. Smal l-bore ETI (tube >8 mm is preferred) 9. I nterference w/chest wal l (e.g. , chest tube, restraints)

VENTILATOR-ASSOCIATED PNEUMON IA 1 . Ventilator-associated pneumonia occurs in 9% to 24% of pts i ntubated >48 hr. 2 . The etiology of venti lator-associated pneumonia varies w/the fol lowing factors: a. Onset 30%) Trauma (>20%) M u ltiple transfusions, blood products Drugs (OD of morphine, methadone, hero i n ; reaction to nitrofurantoin) Noxious in halation (chlorine gas , high 0 2 concentration) Post resuscitation Cardiopul monary bypass Pneumonia TB Burns Pancreatitis

Diagnosis Labs

• ABGs: in itially, varying degrees of hypoxemia, generally resistant to supplemental 02; subsequently, respi ratory alkalosis, ! Pco2, and widened alveolar-arterial gradient. Hypercapnia occurs as the disease progresses . • Hemodynamic mon itoring (when indicated) : Although no hemodynamic profi le is diagnostic of ARDS, the presence of pul monary edema, CO, and ! PAWP is characteristic of ARDS . Imaging

• CXR: Bilateral interstitial infi ltrates are usually seen with i n 24 hr; they are often more promi nent in the bases and periphery. Near-total "wh iteout" of both l ung fields can be seen i n advanced stages. Treatment

• Identification and Rx of the precipitati ng condition • Blood and urine cultures and trial of abx i n presumed sepsis (routine administration of abx i n a l l cases of ARDS is not recommended) • Stabil ization of bone fx i n pts w/major trauma • Bowel rest and crystalloid resuscitation i n pancreatitis • Ventilatory support: A venti lator strategy for pts with ARDS is described i n Figure 1 1 -5 . • Fluid ma nagement: Opti mal fl uid management is pt specific. Swan-Ganz catheterization may be indicated and is useful to guide fl uid replacement. A PCWP of approxi mately 1 2 m m Hg i s idea l . • D VT prophylaxis • Stress ulcer prophylaxis w/sucralfate suspension (by NG tube) or IV PPis or IV H 2 blockers • An algorith m for the i n itial ma nagement of ARDS is described in Figure 1 1 -6.

F. ASTHMA

352 DEFI N ITION The National Asthma Education and Prevention Program (NAEPP) guidelines de­ fi ne asth ma as " a chronic i nflammatory disease of the ai rways i n which many cells

VENTILATORY STRATEGY FOR PATI ENTS WITH ARDS* Goal 1 : Low Vt/Pplat Initiation: Calculate PBW -Male: 50 + 2. 3 (height [inches] - 60) -Female: 45.5 + 2.3 (height [inches] - 60) I nitiate volume assist control -Start with 8 m Ukg, and J, to 6 m Ukg over a few hours

Goal 2 : Ad eq uate Oxygenation

Goal 3: Arterial pH

Specific goal: Pa o2 55-80 mm Hg or Sp 0 2 88-95% u se only F1o2/PEEP combinations shown below to achieve this Iarget • i f oxygenation is low, choose F1o2/PEEP combination (from F1o 2/PEEP table) below • if oxygenation is high, choose F1o2 /PEEP combination to the left

Goal: pH: 7.30-7.45 Acidosis algorithm If pH 7 . 1 5-7.30 • i set rate until pH >7.30 or Paco2 1 8 m m Hg • RR >30 breaths/m in • Tachycardia w/H R > 1 20 bpm

Labs •

•

ABGs can be used in stagi ng the severity of an asthmatic attack: • M i l d : l Pao 2 and Paco 2 , l pH • Moderate: l Pao 2 , nl Paco2 , nl pH • Severe : m a rked l Pao2 , Paco 2 , and l pH Peak flow 1 2 yr and adults is described in Figure 1 1 -7 . The differentiation of asth ma from COPD can be challenging. An hx of atopy and interm ittent, reactive sx poi nts toward a dx of asthma, whereas smoking and advanced age are more indicative of COPD. Spi rometry is useful to distinguish asthma from COPD. Table 1 1 -7 summarizes differentiating features of asthma and COPD.

355

TABLE 1 1 -6 • Classifying Asthma Severity and Initiating Treatment in Youths :!: 1

2 Yr and Adults •

Classification of Asthma Severity (� 1 2 Persistent

Normal FEV1/ FVC: 8- 1 9 yr, 85%; 20-39 yr, 80%; 40-59 yr, 75%; 60-80 yr, 70%

Mild

Moderate

Severe

Symptoms

�2 days/wk

Daily

N ight time awakenings Short-acting �2-agonist use for symptom control (not prevention of E I B) I nterference with normal activity Lung function

�2x/mo

> 2 days/wk but not daily 3-4x/mo

> l x/wk but not nightly Daily

Throughout the day Often 7x/ wk Several times per day

Exacerbations requ i ring oral systemic corticosteroids

Risk

-

Intermittent

Components of Severity Impai rment

yr)

Recommended Step for In itiating

�2 days/wk

>2 days/wk but not daily, and not more than l x on any day

None

Minor limitation

Some limitation

Extremely limited

Normal FEV1 between exacerbations FEV1 >80% predicted

FEV 1 >80% predicted

FEV1 60% but 5%

?.2/yr -1

20o/o

Poor

Good

From Ball mger A: Kumar & Clark's Essentials of Cl1mcal Med1c1ne, 5th ed. Edmburgh , Saunders, 20 1 2 .

357

TABLE 1 1 -8 • Classification of COPD Severity (COLD Criteria)

Stage

Stage 1: mild

Stage I I : moderate Stage I l l : severe

Stage IV: very severe

Function

Symptoms

FEV1 /FVC 1 00 bpm Clinical signs of DVT

1 .5 3

Clinical Judgment

Alternative diagnosis less l i kely than PE

3

Clinical Probability

Total Points

Low Moderate

6

Modified from Wells PS, Gmsberg JS, Anderson DR, et al: Use of a cl1mcal model for safe management of patients with suspected pulmonary embolism. Ann I ntern Med 1 29:997- 1 005, 1 998.

• CHF • Pregnancy and early puerperi um • Visceral cancer (lung, pancreas, a l i mentary and G U tracts) • Spinal cord i nj u ry • Prolonged a i r travel • Central venous catheterization • Advanced age • Obesity, smoking • COPD, DM, acute medical i l l n ess Diagnosis H&.P • • •

• • •

• •

The l i keli hood of PE can be esti mated using Wells c l i n ical pred iction rule (Table 1 1 - 1 0) . Most common physical fi nding: tachypnea Chest pai n : may be nonpleuritic or pleuritic (i nfarction) Syncope (massive PE) Hemoptysis, cough Evidence of DVT: may be present (e.g. , swelling and tenderness of extremities) Cardiac exa m : tachycardia, pulmonic component of S 2 , murmur of tricuspid insufficiency, RV heave, right-sided S 3 Pulmonary exa m : rales, local ized wheezing, friction rub

Labs •

•

•

ABGs: l Pao 2 and Paco2 , l pH A-a 02 gradient (measure of the difference in 02 concentration between alveoli and a rterial blood) : An nl A-a gradient makes the dx of PE u n l i kely. Plasma D-dimer by ELISA: An n l plasma D-dimer level is useful to r/o PE in pts w/ nondiagnostic lung scan and a low pretest probabil ity of PE. However, it cannot " rule i n " PE because it is l w/many other disorders (e.g. , metastatic cancer, trauma, sepsis, postoperative state) .

Imaging •

CXR: l diaphragm , pleural effusion, d i lation of pul monary a rtery, infi ltrate or consolidation, abrupt vessel cutoff, or atelectasis. A wedge-shaped consolidation i n the middle and lower lobes suggests a pulmonary infarction and is known as

Hampton 's hump. • •

360

•

Spira l CT: excellent modal ity for dx PE (Fig. 1 1 -8) . It can also detect other pulmonary disease that can mimic PE. Lung scan (in pt w/nl CXR) : • An nl l u ng scan does r/o PE. • A V/0 mismatch suggests PE, and a l u ng scan i nterpretation of h igh probability is confirmatory. Figure 1 1 -9 is a diagnostic algorithm i ncorporating the Wells criteria , D-di mer testing, and V/0 sca n .

SUSP ECTED PE ( U S I N G CTA) Suspected P E C l inical probabil ity assessment

FIGURE 1 1 -8. Integrated strategy for diagnosis of pulmonary embolism (PE) using clinical probability assessment, measurement of D-dimer, and computer tomography angiography (CTA) as primary imaging test. Patients with low clinical probability (i.e., PE unlikely, negative D-dimer) need no further testing, but if D-dimer is positive, they should proceed to CTA, and if this is nondiagnostic, to ultrasonography of legs. Then either treat or repeat ultrasound in 1 week. Patients with high clinical probability (i.e., PE likely) need not have D-dimer measure but should proceed directly to CTA. If CTA is not diagnostic, options are to perform ultrasonography of legs or proceed to pulmonary angiogram. If ultrasound of legs is negative, options are to repeat in 1 week or proceed to pulmonary angiography. (F'rom Vincent JL, Abraham E, Moore FA, et al [eds]: Texthook of Critical Care, 6th ed. Philadelphia, Saunders, 201 1 .) S U S PECTED PE ( U S I N G

V/Q SCAN)

Suspected PE C l inical probabil ity assessment

FIGURE 1 1 -9 . Integrated strategy for diagnosis of suspected PE using clinical probability assessment, measurement of D-dimer, and V!Q scan as primary imaging test. Patients with low clinical probability (i.e., PE unlikely, negative D-dimer) need no further investigation. If D-dimer is positive, VIQ scan perfmmed; if not diagnostic, proceed to ultrasound. Then either treat or repeat ultrasound in 1 week. Patients with high probability (i.e., PE likely) need not have D-dimer measured but should proceed directly to VIQ scan. If V/Q scan not diagnostic, options are to perform CTA, pulmonary angiography, or ultrasonography of legs. If ultrasonography is 361 negative, either repeat i n 1 week o r perform pulmonary angiogram. (Prom Vincent JL, Abraham E, Moore FA, et al [eds]: Textbook of Critical Care, 6th ed. Philadelphia, Saunders, 201 1 .)

•

•

•

•

Angiography: Pulmonary angiography is the gold standard ; however, it is invasive, expensive, and not read ily ava i lable i n some cli nical setti ngs. False(+) pulmonary angiograms may result from mediastinal disorders such as rad iation fi brosis and tumors. CTA i s a n accurate , n o n i nvasive tool i n the dx of P E at the m a i n , lobar, a n d segmental p u l m o n a ry artery leve l s . A major adva ntage of CTA ove r sta ndard p u l monary angiography is its a b i l ity to dx i ntrath oracic d i sease other than PE that may account for the pt ' s c l i n ical picture. I t i s also l ess i nvasive , less costly, a n d more widely ava i l a b l e . Its major shortcoming is its poor sensitivity for su bsegmental embol i . It is contra i n d i cated i n patients with G F R25 mm Hg at rest or >30 mm Hg w/exercise. Sustained l in PAP second­ ary to pul monary venous pressure, hypoxic pulmonary vasoconstriction , or flow is referred to as secondary pulmonary HTN . Etiology and Classification •

Table 1 1 - 1 1 describes an updated classification of pul monary HTN .

•

Exertional dyspnea: most common presenting sx (60%) Fatigue and weakness Syncope, classica l ly exertion related or after a warm shower w/peripheral vasodi lation Chest pai n Hoarse voice from compression o f recurrent laryngeal nerve b y an enlarged pulmonary artery (Ortner's syndrome) Loud P 2 component of the second heart sound and paradoxical spl itti ng of second heart sound Right-sided S4 JVD Abd distention/ascites Prominent parasternal (RV) i mpulse Holosystolic TR m urm ur heard best along the left fourth parasternal line that l in i ntensity w/i nspiration Peri pheral edema

Diagnosis H&P • • • • • •

• •

•

•

•

Labs •

•

•

•

•

CBC: nl or may show secondary polycythemia ANA (r/o connective tissue disease) , H IV, LFTs, anti phosphol ipid Abs ABGs: l Po2 and Sao2 PFTs: r/o obstructive or restrictive l ung disease Overn ight sleep study: r/o sleep apnea/hypopnea

Imaging • •

•

362

•

ECG : RA enlargement (tall P wave >2 . 5 mV i n leads I I , I l l , aVF) and RV enlargement (RAD > 1 00 and R wave > S wave i n lead V j ) CXR: enlargement o f the m a i n a n d h i lar pulmonary a rteries w/ra pid tapering of the distal vessels, described as peri pheral olige m i a . RV enlargement may be evident on latera l fi lms. Spira l CT or V/0 sca n : r/o PE Doppler echo: assesses ventricular function, excl udes sign ificant valvular d isease, and visual izes abnl shunting of blood between heart chambers if present. It also provides an esti mate of the pulmonary artery systolic pressure.

TABLE 1 1 - 1 1 • Updated Clinical Classification of Pulmonary Hypertension

Croup 1

Pulmonary Arterial Hypertension (PAH)

Idiopathic PAH Heritable BM PR2 ALK 1 , endoglin (with or without hereditary hemorrhagic telangiectasia) Unknown Drug- and toxin-induced Associated with Connective tissue diseases H IV infection Portal hypertension Congenital heart diseases Schistosomiasis Chronic hemolytic anemia Persistent Pulmonary Hypertension of the Newborn Pulmonary Vena-occlusive Disease with Left-to-Right Shunts and/or Pulmonary Capillary Heman­ giomatosis

Croup 2

Pulmonary Hypertension Secondary to Left-Sided Heart Disease

Systolic dysfunction Diastolic dysfunction Valvular disease

Croup 3 Pulmonary Hypertension Secondary to Lung Diseases and/or Hypoxia

COPD I nterstitial lung disease Other Pulmonary Diseases with Mixed Restrictive and Obstructive Pattern

Sleep-disordered breathing Alveolar hypoventilation disorders Chronic exposure to high altitude Developmental abnormalities

Croup 4

Chronic Thromboembolic Pulmonary Hypertension {50% have no hx of DVT/PE)

Croup 5

Pulmonary Hypertension with Unclear Multifactorial Mechanisms

Hematologic disorders: myeloproliferative disorders, splenectomy Systemic disorders: sarcoidosis, pulmonary Langerhans cell histiocytosis: lymphangioleiomyomatosis, neurofi bromatosis, vasculitis Metabolic disorders: glycogen storage disease, Gaucher's disease, thyroid disorders Others: tumoral obstruction, fibrosing mediastinitis, chronic renal failure on dialysis Modified From Simonneau G et al: U pdated clinical classification of pulmonary hypertension. J Am Coli Cardia! 54: 543-554, 2009. ALK I , Activin receptor-li ke kinase type 1 ; BMPR2, bone morphogenetic protei n receptor type 2.

Treatment Acute Rx •

•

•

Diuretics (e.g. , furosemide 40-80 mg qd) Digoxi n i n pts w/AF Short-acting vasod ilators: IV adenosine, epoprostenol, or i n haled n itric oxide

Chronic Rx • • •

•

• •

CCB (di ltiazem , amlodipine, or nifed ipine) Prostanoids (epoprostenol , treprost i n i l , and iloprost) act as potent vasodilators of pulmonary arteries and inhibitors of Pit aggregation . Endothelin receptor antagonists: bosenta n , ambrisenta n , and sitaxsentan Phosphodiesterase i n h ibitors: sildenafi l and tadalafi l Warfari n Rx w/goal I N R 1 . 5 to 2 . 0 is recommended for all pts w/PPH and although not proven may be indicated in secondary pulmonary HTN . Lung transplantation and heart-lung transplantation are other options in pts w/ end-stage class IV disease . Atrial septostomy may be performed as a bridge to transplantation.

363

TABLE 1 1 - 1 2 • Overview of Idiopathic Interstitial Pneumonias

Diagnosis

Clinical Findings

HRCT Features

U I P/IPF

40-70 yr, M>F; >6-mo dyspnea, cough, crackles, clubbing; poor response to steroids

Peripheral, basal, subpleural reticulation and honeycombing, ± groundglass opacity

NSIP

40-50 y r , M F; dyspnea, cough , fatigue, crackles; may respond t o steroids 30-50 yr, M > F; dyspnea, cough

Bilateral, patchy, subpleural ground-glass opacity, ± reticulation Ground-glass, centrilobular nodules, ± centrilobular emphysema Ground-glass consolidation, traction bronchiectasis, and architectural distortion Subpleural and peribronchial consolidation, ± nodules i n lower zones; atoll sign (ring-shaped opacity) Ground-glass opacity, lower zone, peripheral

RB-ILD

=

Al P/diffuse alveolar damage

Any age, M F; acute-onset dyspnea, diffuse crackles and consol idation

COP

Mean 55 yr, M F; F; insidious onset weeks to months of dyspnea, cough

LIP

Any age, F > M

=

=

Ground-glass opacity, ± poorly defined centrilobular nodules, thi n-walled cysts, and air trapping

-

Differential Diagnosis

Collagen vascular disease, asbestosis, CHP, scleroderma, drugs (bleomycin , methotrexate) Collagen vascular disease, CHP, D I P Hypersensitivity pneumonitis ARDS, i nfection , edema, hemorrhage

Collagen vascular disease, infection, vasculitis, sarcoidosis, lymphoma, alveolar carcinoma Hypersensitivity pneumonitis, N S I P D I P, N S I P , hypersensitivity pneumonitis

From Ferri F: Ferri 's Clin ical Advisor: 5 Books in 1 . 20 1 3 edition. Philadelphia, Mosby, 20 1 2 . AlP, Acute interstitial pneumonia; CHP, chronic hypersensitivity pneumonitis; COP, cryptogenic organizing pneumonia; DIP, desquamative interstitial pneumonitis; IPF, idiopathic pulmonary fibrosis; LIP, lymphoid interstitial pneumonia; NSIP, nonspecific i nterstitial pneumonia; RB-ILD, respiratory bronchiolitis-associated i nterstitial lung disease; VIP,

usual interstitial pneumonia.

I. DIFFUSE PARENCHYMAL LUNG

DISEASE 0 I NTERSTITIAL LUNG DISEASE (ILD) I LD includes a large group of nonmal ignant disorders characterized by diffuse damage to the lung parenchyma by i nflam mation and fibrosis or granulomatous reaction i n i nterstitial or vascular areas. Table 1 1 - 1 2 provides an overview o f idiopath ic i nter­ stitial pneumonias. Diagnosis H&.P • • •

•

•

Dyspnea Tachypnea Bibasilar end-inspiratory d ry crackles Pulmonary HTN Cyanosis, c l u bbing

Labs •

• •

•

ABGs: nl or may show respi ratory alkalosis ANA, ANCA, ACE leve l , RF, LDH Bronchoscopy and BAL may help identify type of I LD . However, their role in defi n i ng the stage of disease and the response to Rx is controversia l . B x i s t h e most effective method for confirming dx and assessi ng disease activity.

Imaging (Box 1 1 -5) • •

364

CXR, H RCT: bibasilar reticular pattern PFTs: Well-defined patterns in PFTs are usually consistent w/restrictive defect (! FRC, RV, and TLC) resulting from ! lung compliance caused by alveolar wall thickening from inflammation and fibrosis. Diffusing capacity l from inflammation and thickening of alveolar walls, although nonspecific. FEV1 /FVC is usually nl or because lung stiffness keeps small airways open, although some conditions (e.g. , sarcoidosis) may l airflow.

Box l l-5 • Radiographic Features That Suggest Specific Causes of Interstitial Lung Disease Bllar or Mediastinal Lymphadenopathy

Sarcoidosis Berylliosis Silicosis (eggshell calcification) Lymphocytic interstitial pneumonia Amyloidosis Gaucher's disease Plenral Disease

Asbestosis (pleural effusion, thickening, plaques, mesothelioma) Systemic rheumatic disorders Lymphangioleiomyomatosis (chylous effusion) Nitrofurantoin Radiation pneumonitis Pnenmothorax

Histiocytosis X Lymphangioleiomyomatosis Neurofibromatosis Tuberous sclerosis Preserved Long Volnmes or Hyperinflation

Bronchiolitis obliterans organizing pneumonia Chronic hypersensitivity pneumonitis Histiocytosis X Lymphangioleiomyomatosis Neurofibromatosis Sarcoidosis Tuberous sclerosis Upper Lobe Distribntlon

Ankylosing spondylitis Berylliosis Histiocytosis X Silicosis Chronic hypersensitivity pneumonitis Necrobiotic nodules of rheumatoid arthritis Fmm Goldman L, AusieUo D (eds): Cecil Textbook of Medicine, 22nd ed. Philadelphia, Saunders, 2004.

Treatment •

•

Predn isone 0 . 5 to 1 mg/kg qd x 4 to 1 2 wk, then re-eval uate ; if stable, taper; if not, maintain x another 4 to 1 2 wk; if sti l l not i m proved, add cyclophosphamide or azath ioprine. Supplemental 0 2 PRN i n pts w/hypoxemia; avoidance of tobacco and occupational exposures

J. GRANULOMATOUS LUNG DISEASE 0 SARCOIDOSIS Chronic systemic granulomatous disease of unknown cause, characterized histologi­ cally by the presence of nonspecific, noncaseati ng granulomas Diagnosis H&P •

Clinical man ifestations often vary w/stage of the d i sease and degree of organ involvement; pts may be asymptomatic, but CXR may demonstrate fi ndi ngs consistent w/sarcoidosis (see the later section on imaging) . Nearly 50% of pts w/ sarcoidosis are dx by incidental fi ndi ngs on CXR. Frequent man ifestations: • Pulmonary man ifestations: dry, non productive cough ; dyspnea; chest discomfort • Constitutional sx: fatigue, weight loss, anorexia , malaise • Visual disturbances: b l u rred vision, ocular discomfort, conjunctivitis, i ritis, uveitis (65% of pts) • Dermatologic manifestations: erythema nodosum ( 1 0% of pts) , macules, papules, 365 SC nodules, hyperpigmentation, lupus pern io (indurated violaceous lesions on the nose, l ips, ears , cheeks that can erode into underlying carti lage and bone) • Myocardial disturbances (5% of pts) : arrhyth mias, cardiomyopathy

• Splenomegaly, hepatomegaly • Rheumatologic manifestations: arthralgias have been reported in up to 40o/o of pts • Neurologic and other man ifestations: cranial nerve palsies, diabetes i nsipidus, meni ngeal i nvolvement, parotid enlargement, hypothalamic and pituitary lesions, peri pheral adenopathy Labs • •

•

•

Hypergam maglobulinemia, anemia, leukopenia LFT abnlities Hypercalcemia ( 1 1 o/o of pts) , hypercalciuria (40o/o of pts) : secondary to G l absorption, abnl vita m i n D metabolism, and calcitriol prod uction by sarcoid gra n u loma ACE i n 60o/o of pts; nonspecific and generally not usefu l as a dx tool and in fol lowing the course of the disease

Imaging •

• • •

CXR and chest CT • Adenopathy of the hilar and paratracheal nodes • Parenchymal changes may also be present, depending on the stage of the disease: stage 0, n l x-ray; stage I, bilateral hilar adenopathy; stage I I , stage I plus pulmonary infi ltrate; stage I l l , pul monary i nfiltrate w/o adenopathy; stage IV, advanced fibrosis w/evidence of honeycombi ng, h i lar retraction, bullae, cysts, and em physema. PFTs (spi rometry and diffusing capacity of the l u ng for CO) : may be n l or may reveal a restrictive pattern or obstructive pattern 1 8 FDG-PET: useful i n identifyi ng sites for dx bx i n pts w/o apparent l u ng i nvolvement 1 8 FDG-PET and M R I w/gadoli n i u m : useful in pts w/suspected cardiac and neurologic involvement

Treatment •

•

• • •

Most pts wi l l not requ i re any Rx. Corticosteroids should be considered in pts w/severe sx (e.g. , dyspnea ; chest pai n ; hypercalcemia; ocular, C N S , or cardiac i nvolvement; a n d progressive pul monary disease) . MTX 7 . 5 to 1 5 mg once/wk: in pts w/progressive disease refractory to corticosteroids Hydroxychloroquine: effective for chronic disfiguring skin lesions, hypercalcemia, and neurologic i nvolvement NSAI Ds: useful for musculoskeletal sx and erythema nodosum

Prognosis •

•

Most pts w/sarcoidosis have sponta neous rem i ssion with i n 2 yr and do not req u i re Rx. The i r course can be fol l owed by period i c c l i n ical eva l uati o n , CXR , a n d PFTs . However, 2 5o/o to 33o/o of pts have unrelenting disease leading to clin ically significant organ impairment. Adverse prognostic factors are age at onset >40 yr, cardiac i nvolvement, neurosarcoidosis, progressive pul monary fibrosis, chronic hypercalcemia, chronic uveitis, i nvolvement of nasal m ucosa, nephrocalci nosis, and presence of cystic bone lesions and lupus pernio.

0 G RANULOMATOSIS WITH POLVANG I ITIS (WEG ENER'S G RAN ULOMATOSIS) •

•

M u ltisystem disease generally consisting of the classic triad of: • Necrotizing granulomatous lesions in the upper or lower respi ratory tracts • Generalized focal necrotizi ng vasculitis i nvolving both arteries and veins • Focal G N of the kidneys " Li m ited forms" of the disease can also occur and may evolve i nto the classic triad. G ranulomatosis with polyangi itis can be classified by the " ELK" classification, which identifies the three major sites of i nvolvement: E, ears, nose, and throat or respiratory tract; L, l u ngs; K, kidneys.

Diagnosis H&.P •

366

•

Clin ical manifestations often vary w/the stage of the disease and degree of organ i nvolvement. Frequent manifestations: • U pper respiratory tract: chronic sin usitis, chronic otitis media, mastoiditis, nasal crusting, obstruction and epistaxis, nasal septal perforation , nasal lacri mal duct stenosis, saddle nose deform ities (resulting from cartilage destruction)

• Lung: hemoptysis, m u ltiple nodules, diffuse alveolar pattern • Kidney: renal insufficiency, GN • Ski n : necrotizing skin lesions • Nervous system : mononeuritis m u ltiplex, cranial nerve i nvolvement • J o i nts: monarthritis or polyarthritis (nondeform i ng) , usually affecting l a rge j o i nts • Mouth : chronic ulcerative lesions of the oral mucosa , " m u lberry" gingivitis • Eye : proptosis, uveitis, episcleritis, retinal and optic nerve vasc u l itis Labs •

•

•

(+) test result for cytoplasmic pattern of ANCA (cANCA) Other labs: anemia, leukocytosis, hematuria, RBC casts, and proteinuria; l serum Cr, l CrCI , l ESR, (+) RF, and l CRP Bx of one or more affected organs should be attempted ; the most rel iable source for tissue dx is the l u ng. Lesions in the nasopharynx (if present) can be easily sampled.

Imaging •

•

CXR: bi lateral m u ltiple nodules, cavitated mass lesions, pleural effusion (20%) PFTs: useful i n detecting stenosis of the a i rways

Treatment •

•

Predn isone 60 to 80 mg/day and cyclophosphamide 2 mg/kg. Once the disease i s u n d e r contro l , predn isone is tapered a n d cyclophosphamide is conti nued. Other potentially usefu l agents i n pts intolerant of cyclophosphamide are azathioprine, MTX, and mycophenolate mofeti l . TM P-SMX: useful alternative i n pts w/lesions l i m ited t o the u pper o r lower respi ratory tracts in absence of vasculitis or neph ritis. Rx w/TM P-SMX ( 1 60 mg/800 mg bid) also l the incidence of relapses i n pts w/Wegener's granulomatosis in remission. It is also usefu l in preventing Pneumocystis pneumonia, which occurs i n 1 0% of pts receiving ind uction Rx. When used for prophylaxis, dose of TM P-SMX ( 1 60 mg/800 mg) is 1 tablet 3x/wk.

I::J PLEURAL DISEASE

1 Pleural EffusionfThoracentesis Indications

1 . Presence of any pleural effusion of unknown cause 2. Relief of dyspnea caused by large pleural effusion Contraindications

1 . Clotting abnlities 2. Thrombocytopenia 3 . U ncooperative pt or pt w/severe cough or hiccups Localization of Pleural Effusion

1 . Physical exami natio n : d u l l ness to percussion, loss of tacti le frem itus 2. CXR: PA view is usually sufficient i n identifyi ng the fl uid collection ; but i n case of equivocal effusions, a lateral decubitus CXR can demonstrate layering out of the pleural fl uid. Effusions > 1 em on a lateral decubitus fi l m are usually sufficiently large to be removed at the bedside w/o additional i maging. 3. Fluoroscopy, u ltrasonography, or CT guidance i n performing thoracentesis if the fl uid collection has the fol lowing qual ities: a. 1 000 m l of fl uid at any one time because of risk of pulmonary edema or hypotension (pneumothorax from needle laceration of the visceral pleura is also much more l i kely to occur if an effusion is completely drained). 1 2 . Gently remove the need le. 1 3 . Obta in measurements of serum LDH , alb, glucose, and total protein levels. 1 4. Process the pleural fl uid; the i n itial laboratory studies should be ai med only at disti nguish i ng an exudate from a transudate (Fig. 1 1 - 1 0) . a . Tube 1 : protein, LDH , alb b . Tubes 2 , 3 , 4: Save the fl uid until further notice. I n selected pts w/suspected empyema, ascerta i n i ng a pH level may be useful (generally 2 L, or if the maxi mal vol untary venti lation is >50% of predicted capacity. Individuals w/FEV 1 > 1 . 5 L are su itable for lobectomy w/o further eva luation un less there is evidence of I LD or undue dyspnea on exertion . I n that case , D Lco should be measured . If the DLco is 40% , surgery is possi ble. Genetic mutations testing of lung specimen: detection of epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) =

•

Imaging •

• • •

CXR CT chest PET wf 1 8 F-fl uorodeoxygl ucose ( 1 8 FDG-PET) : for preop stagi ng of NSCLC CT of l iver and bra i n ; bone scan in a l l pts w/SC LC and pts w/NSCLC suspected of involving these organs

Staging •

•

The i nternational stagi ng system for N SCLC : Stage I is NO (no lymph node i nvolvement) . Stage II (N 1 [spread to ipsilateral bronchopulmonary or hilar lym ph nodes]) incl udes localized tumors for which surgical resection is the preferred Rx. Stage I l l is subdivided i nto l i lA (potentially resectable) and I I I B . The surgical management o f stage l i lA disease ( N 2 [ i nvolvement o f ipsilateral mediastinal nodes]) is controversial . Only 20% of N2 disease is considered m i n imal disease (i nvolvement of only one node) and techn ically resectable. Stage IV indicates metastatic disease. The pathologic staging system uses a tumor-nodal i nvolvement-metastasis system . In pts w/SCLC , the stagi ng system from the Veterans Administration Lung Cancer Study G roup contains two stages: • Lim ited stage disease: confi ned to the regional lymph nodes and to one hem ithorax (excluding pleural surfaces) • Extensive stage disease: spread beyond the confi nes of l i m ited-stage disease

Treatment NSCLC

370

•

Surgical resection (lobectomy, pneumonectomy) • I ndicated in pts w/l i mited disease (stage I or I I ) . This represents 1 5% to 30% of diagnosed cases . Lobectomy can be performed by VATS with less morbid ity and shorter hospitalization.

•

• Preoperative chemoRx: consider i n pts w/more advanced disease (stage l i lA) who are being considered for surgery. Gene expression profi les that predict the risk of recurrence i n pts w/early-stage ( lA) NSCLC have been identified. These pts are at h igh risk for recurrence and may also benefit from adjuvant chemoRx. • Postoperative adj uvant chemoRx (chemoRx given after surgical resection of an apparently localized tumor to eradicate occult mets) w/vinorelbine plus cisplati n : consider i n pts w/completely resected stage I B or stage I I NSCLC a n d good performance status. Adj uvant chemoRx is generally i ndicated for pts w/resected tumors that are stages I lA through l i lA. Rx of u n resectable NSCLC • RadioRx can be used alone or in combi nation w/chemoRx; it is used primarily for Rx of CNS and skeletal mets, SVC, and obstructive atelectasis. Although thoracic radioRx i s generally considered standard Rx for stage I l l disease, it has l i m ited effect on surviva l . Pall iative radioRx should be delayed until sx occur because i mmediate Rx offers no advantage over delayed Rx and results i n more adverse events from the rad ioRx. • ChemoRx: Current drugs of choice are pacl itaxel + either carboplatin or cisplatin ; cisplatin + vinorelbine; gemcitabine + cisplati n ; carboplatin or cisplati n + docetaxel . The overall results are disappoi nting, and none of the standard regi mens for NSCLC is clearly su perior to the others. The addition of bevacizumab to paclitaxel + carboplatin resu lts i n sign ificant surviva l benefit but carries a risk of Rx-related death. Gefiti nib and erlotinib are PO inhi bitors of EGFR tyrosine kinase. Both agents are approved only for pts i n whom at least one prior chemoRx regi men has failed. The i n h ibition of ALK in lung tumors with crizotin i b , an orally avai lable small-molecule i n h i bitor o f t h e A L K tyrosine kinase , has resulted i n tumor shrinkage and signifi cantly prolonged progression-free surviva l . • T h e addition o f chemoRx t o radioRx improves surviva l i n pts w/locally advanced, unresectable N SCLC . The absol ute benefit is relatively smal l , however, and should be balanced agai nst the toxicity associated w/the addition of chemoRx.

SCLC • • •

Li mited stage disease : standard Rxs incl ude thoracic radioRx and chemoRx (cisplati n and etoposide) Extensive stage disease : standard Rxs incl ude combi nation chemoRx (cisplatin or carboplatin + etoposide or combination of irinotecan and cisplatin) Prophylactic cranial i rrad iation: for pts in complete rem ission to l the risk of CNS metastasis

M. RESPIRATORY FAILURE

CLASSIFICATION It! HYPOXEMIC ("TYPE I") RESPIRATORY FAILURE • •

•

•

l in oxyhemoglobin that does not correct with supp. 0 2 Pa02 (ambient air) :o; 60 mmHg PC0 2 typically normal or < 40 mmHg Hypoxemia is the result of persistent perfusion of l ung u n its that are not venti lating as a result of fl uid (pus, blood , edema) or alveolar collapse => intrapul monary shunt physiology results in inabil ity to correct with supp. 0 2 . Hypoxem ia can be corrected with administration of PEEP which " results" and opens up collapsed/ fl i ud-fi l led alveo l i . • Exam ples: ARDS, C H F , Atelectasis, Pneumonia

[! HYPERCAPNIC ("TYPE I I " ) RESPIRATORY FAILURE •

• •

Occurs as a result of insufficient alveolar venti lation from iC0 2 Pa0 2 l PC02 i as a result of iC02 production and/or decreased alveolar ventilation (secondary to respiratory m uscle weakness/excessive mechanical work of breath i ng, decreased respi ratory drive, and l ung diseases with i m paired gas exchange such as: COPD) • Examples: COPD/Asthma (obstructive l ung disease) , Neuromuscular disease (Myasthenia Gravis, GBS when VC < 1 5-20 cc/kg and N I F < 30) . Restrictive Lung Disease (Extrapulmonary - kyphoscoliosis, ascites, and I ntrapulmonary - Fibrotic Lung disease)

371

A. ARTHOCENTESIS INDICATIONS

1. 2. 3. 4. 5.

Presence of effusion of unexplained etiology Steroid injection Decom pression of a hemorrhagic effusion i n traumatized joi nts Eval uation of abx response in pts w/infectious arthritis Removal of purulent fl uid i n d istended infected joints

CONTRAI NDICATIONS 1 . Cel l u l itis or broken skin over the i ntended entry site 2. Coagulopathy 3. Unstable joint

PROCEDURE 1 . Pal pate the joint and identify the extensor surface (vessels and nerves are less commonly found here) . 2 . With fi rm pressure, use a bal l point pen that has the writing portion retracted to mark the specifi c area of the joint to be aspirated. 3 . Clean the skin w/an antiseptic sol ution . 4. Use a 25-gauge needle to i nfiltrate the skin w/ 1 % to 2% l idocaine. 5 . Gently insert an 1 8- or 20-gauge needle connected to a 20- to 30-m l syringe; a sl ight " pop" may be felt as the needle penetrates the capsule. 6. Apply gentle suction to the syri nge to aspi rate the fl u i d . 7 . Gently remove t h e needle, and a p p l y sl ight pressure t o t h e puncture site. 8. Process the aspirated synovial fl u i d : a . Tube 1 (no hepari n ) : viscosity, mucin clot b . Tube 2 (conta i n i ng hepari n) : gl ucose level c. Tube 3 (conta i n i ng hepari n) : G ram sta i n , C&S, cytology, CBC w/diff d . Glass slide: Place a drop of fl uid and examine under polarized l ight. e . Plate w/Thayer-Martin med i u m (used in cases of suspected gonococcal arth ritis) ; assessment for Lyme titer, cu ltures for anaerobes, Mycobacterium tuberculosis, and fungi should be ordered only when clearly indicated. 9. Draw samples for measurement of serum gl ucose leve l .

INTERPRETATION OF RESULTS 1 . Color: Normally it is clear or pale yellow; cloudiness ind icates an i nflammatory process or presence of crystals, cell debris, fibri n , or TGs. 2 . Viscosity is h igh because of hyaluronate ; when fl uid is placed on a slide, it can be stretched to a string longer than 2 em before separating (low viscosity indicates breakdown of hyaluronate [ lysosomal enzymes from leukocytes] or the presence of edema fl uid). 3 . Mucin clot: Add 1 m l of fl uid to 5 m l of a 5% acetic acid solution , and al low 1 min for the clot to form ; a firm clot (does not fragment on shaki ng) is nl and indicates the presence of large molecules of hya l u ronic acid (th is test is nonspecific and i nfrequently done) . 4. Gl ucose leve l : nl is approxi mately = serum gl ucose leve l ; a difference of >40 mg/ dl suggests infection . 5. Total protein concentration is Look for i nflammation w/contrast M RI and P ET scans Low-dose aspirin Treat lipids aggressively to prevent atherosclerosis

TABL.f 1 2- 1 • Systemic Vasculltls-cont'd

Medium-Vessel

Polyarteriti s Nodosa

Clinical Features/Dx

I nflam mati on and n ecrosis of medi um-sized and small m uscular artery walls Age of onset: 40-60 yr S O % cases associated with Hep B

Fever, arthralgia, myalgia, abd pain , wt loss Periph eral nerve: mononeu ritis m u lti plex HTN ± renoarteriolar i nvolvement Testicular pain , pai nful cutaneous nodules/skin ulcers/palpable purpuranivedo reticularis Spares l ungs Dx:

Mana ement

H igh-dose corticosteroids x several weeks w/slow taper followi ng U se cyclophosphamide i n patients who do not respond I n hep B(+) patients, give short course ( 1 -2 wk) of steroids w/antivi ral Rx (entecavir) (>50% H BeAg(+) Pts w/polyarteritis nodosa respond w/resolution of arteritis and seroconversion to hep B e-antibody positivity

P-ANCA Necrotizing arteritis on bx specimens of i nvolved skin , sural nerve (do not u se kidney given ri sk of hemorrhage) Aneurysms and stenoses on CTA Kawasaki's D isease

U sually occurs in children Seen in adu lts w/H IV

Small-Vessel Wegener's Granulomatosis (Granulomatosis w/Polyangiitis)

Involvement of small to medium-sized arteries and can be a ssociated w/a " pauci-i mmune" (no imm une complexes) G N

Fever >5 days + nonexudative conju nctivitis, erythema of oral mucosa Edema of extremities w/desquamation ACS or peri pheral vascular occlusion Coronary aneu rysm s (MC i n chil dren) Ox: made by cli nical featu res

Clinical Features/Ox

Mana ement

Upper airway disease (70%): sinusitis , epistaxis, and nasal septal perforation/saddle nose deformity ± carti lage erosion Pu lmonary: cough , hemoptysis, pleurisy, mu ltifocal infi ltrates or nodules on CXR Ocular symptoms: scl eritis , uveitis, keratitis Purpura, u lcers on skin Pauci-i mmune GN (80%)

H igh-dose corticosteroids w/3-6-mo course of cyclophosph amide B-ce ll de pletion Rx w/rituximab has been shown to be equally as effective as cyclop hosphamide Following remission: steroids are tapered and cyclophosphamide is stopped => Rx is continued for 1 8 mo w/azathioprine or wkly MTX (90% achieve rem ission, relapses are frequent w/MTX) Bactrim for PCP prophylaxis

Ox:

C-ANCA Established by kidney or l u ng bx Antip rotei nase-3 Abs'

I�

H igh-dose sal icylates and early admin istration of IVIG TIE to r/o coronary a rtery aneu rysm

Continued

I�

TABLE 1 2- 1 • Systemic Vasculltls-cont'd

Small-Vessel

Pathophysiology

Clinical Features/Ox

Management

Microscopic Polyangiiti s

Necrotizing vascu litis that predomi nantly affects the lu ngs and kidneys Age of onset: 3 0-50 yr

Fever, arthralgia, purpuric skin rash, mon oneuritis mu ltiplex Rapidly progressive GN or pulmon ary hemorrhage

H igh-dose corticosteroids + cyclop hosphamide OR rituximab Fol lowing remission, those treated w/cyclophosphamide should transition to azathioprine or wkly MTX

Ch urg-Strau ss Syn drome

Systemic vascul itis in the spectrum of hypereo­ sinoph i l ic disorders

Ox:

P-ANCA Antimyeloperoxidase Ab (60%-80%) Confirm w/bx of affected tissue (skin , lung, kidney) : lung: p u l monary capillaritis; kidney: pauci-immune or diffu se necrotizing G N similar to Wegener 's; skin : necrotizing arteritis of arte rioles Most often occu rs in setting of antecedent asth ma, allergic rh initis, sinusitis Eosinophilia (> 1 Oo/o) M igratory pul monary infiltrates Fever, arthralgias, myalgias, pu rpura Ox:

Henoch-Schon lei n Purpura

"Systemic" l gA nephropathy Usual ly occurs i n children In men >50 yr old, l ook out for association w/ solid tumors or M DS

P-ANCA (50%); usually have pauci-im mune GN and monon euritis Established by bx and confirmed eosinophil ic tissue infiltratio n Pal pable p urpu ra affecting d istal LEs Abdominal pain , a rthritis Hematu ria/proteinuria Usually self-l imiting Ox:

Confirm w/bx of affected tissue (skin , l ung, kidney) : ski n : sh ows presence of leukocytoclastic vasculitis w/lgA deposits; kidney: G N w/lgA deposition

H igh-dose corticosteroids allow full rem ission i n 80-90% Oral or IV cyclophosphamide is recommended in pts w/ne uro, G l , rena l , or cardiac involvement Maintena nce Rx w/azath i oprine or MTX for 1 2 - 1 8 mo fol­ l owing remission

Sh ort course of moderate-dose steroids (20-40 mg/day of prednisone) Decreases duration and severity of skin and joint symptoms associated w/HSP I n patie nts w/prol iferative GN give high-dose steroids and monthly cyclophosphamide

TABLE 1 2 - 1 • Systemic Vasculltl�nt'd

--

Small-Vessel

Pathophysiology

Clinical Features/Ox

Management

Essential Cryoglobu l in­ ernie Vascu litis

Imm unoglobu lins that precipitate from serum in the cold Type I cryoglobulins: monoc lona l , self­ aggregate, associated w/Waldenstrom ' s and MM; associated w/hyperviscosity Type II cryoglobulins: monoclona l lgM or lgA rheu matoid factors that bind to Fe of lgG, associated w/hep C and H IV Type I I cryoglobu l i n s : see n in setting of a uto­ immune disorders (SLE, Sjogren ' s , RA)

Palpable purpu ra , mononeuriti s m ultiplex LAD, H S M Renal failure ± G N

Hep (-associated cryoglobulinemia responds to antiviral therapy w/interferon alfa + ribavirin Short course of corticosteroids In patients with renal failure, digital gangrene, neuro disease, 2-3-wk course of plasma exchange recommended

Cutaneous Leukocyto­ clastic Vasculitis

Seen in pts w/con nective tissue diseases and as a reaction to drugs/viruses 40o/o idiopath ic 60o/o ± autoimmune disease (SLE). drugs, infec­ tion, h ematologic malignancy

Ox:

! C3 , C4 (immune-complex GN)

80o/o of type-1 1 cryoglobulinemic vascul iti s i s associated w/hep C

Palpable purpura , tender nodules , persistent u rticaria, or s ha l l ow ulc ers Lesions seen most commonly on distal LEs Ox:

Neutrophils and mon on uclear cells invading the walls of dermal capillaries, arterioles, and ve nules seen o n bx

*Vascul itis: Infla mmation of blood vessel wall s that causes vessel narrowing/occ lusion, ane urysm, or rupture .

I�

Removal of offending drugs or treatment of the i nfectious etiology Favorably responds to N SAI Ds, colch icine, or dapsone Manage urticarial lesions w/combining antih istamines ( H 1 and H 2 blockers)

Etiology •

•

The exact etiology and pathogenesis a re uncerta i n . Genetic susceptibil ity t o l u p u s is l i kely i nherited as a polygenic trait. M u ltiple genetic l i n kages including 1 q23, 2q35-37 , 6p2 1 - 1 1 , and 1 2q24 show strong associations with SLE. Environmental factors such as u ltraviolet l ight exposure and Epstei n-Barr virus infection may have a triggering role. Autoantibodies can be present years before the diagnosis of SLE. Evidence supports the improper processing of n uclear proteins and nucleic acid from program med cell death . Th is leads to the presentation of self-DNA to plasmacytoid dendritic cells. Plasmacytoid dendritic cells propagate antibody and immune complex production and other arms of specific autoimmun ity.

Diagnosis H&P •

•

• •

•

•

•

•

•

Constitutiona l : unexplained fever, fatigue, malaise Ski n : malar rash sparing nasolabial folds (acute cutaneous lupus) , a n n u lar or papulosquamous rash (subacute cutaneous lupus) , raised e rythematous patches with subsequent edematous plaques and adherent scales (discoid cutaneous lupus) ; alopecia, nasa l , or oropharyngeal u lcerations; Rayna u d ' s phenomenon ; petechiae, palpable purpura , skin ulceration, or d igital ischemia (vasculitis) ; l ivedo reticularis or l ivedo racemosa (secondary a nti phospholipid anti body synd rome) Musculoskeleta l : arthritis (tenderness, swe l l i ng, effusion) typically affecting peri pheral joi nts; myositis Cardiac: pericardia! rub (pericard itis) , heart murmur (Libman-Sachs endocarditis and other valvular heart disease) , congestive heart fai l u re (myocarditis) , premature atherosclerotic heart disease Pulmonary: pleuritis, pneumonitis, diffuse alveolar hemorrhage Gastroi ntesti nal: abdom inal pai n , intesti nal vasculitis, ascites Neurologic : headache, psychosis, seizure, acute confusional states, peri pheral or cranial neuropathy, transverse myel itis, CVA, chronic cognitive impairment Hematologic : anemia (hemolytic, anemia of chronic disease, aplastic anemia), throm bocytopen ia, leukopenia, lymphadenopathy, secondary antiphospholipid antibody syndrome Renal: ARF, proteinuria, nephritic syndrome, nephrotic syndrome

W!Up •

3 78

The diagnosis of SLE is suspected when any four or more of the fol lowing 1 997 American College of Rheumatology criteria are present: • Malar rash • Discoid rash • Photosensitivity (recu rrence of u n usual skin rash in sun exposed areas) • Oral or nasopharyngeal painless ulceration • Arthritis • Serositis (pleuritis, pericarditis) • Renal disorder (persistent protein uria >0 . 5 g/day, or 3+ on di pstick if quantitation not performed; cellular casts) • Neurologic disorder (seizures, psychosis [ i n absence of offending drugs or metabolic derangement]) • Hematologic disorder: • Hemolytic anemia with reticulocytosis • Leukopenia (6 wk ( 1 poi nt) • Scores �6 poi nts are considered to have " defi n ite RA. " Max score is 1 0 poi nts.

H&P •

•

•

•

380

I n itial presentation: • Pts have >6 wk of pai n , swe l l i ng, warmth i n one or more peri pheral joints, frequently with sym metric joint involvement i nvolving wrists, hands and/or feet, and often associated with > 1 hr of morni ng stiffness. • Most commonly i nvolved joi nts i nclude MCP, P I P , wrists, MTP, and ankles. • The elbows, shoulders, h i ps, and knees are also affected . • D I P joi nts are spared . • Sacroil iac and vertebral joints are spared except for C 1 to C2. Chronic long-standing disease : • "Swan-neck" ( D I P flexion and P I P hyperextension) and "boutonniere" ( P I P flexion and D I P hyperextension) deformities occur, as w e l l as MCP subl uxation resulting i n ulnar drift. • C 1 to C2 i nflam mation can lead to odontoid erosion and transverse l igament laxity, resulting in atlantoaxial subl uxation and cord compression . • Joint damage of wrists, el bows, shoulders, h i ps, and knees can lead to severe osteoarthritis, necessitating joint surgery and/or replacement. Extra-articular man ifestations: • Secondary Sjogre n ' s synd rome (-35%) : immune-med iated inflammation of lacri mal and sal ivary glands resulting i n dry mouth and eyes (sicca syndrome) • Rheumatoid nodules (25o/o) : on extensor surfaces and pressure points, i n RF(+) disease . Histopathology demonstrates palisading histiocytes surrounding fi brinoid necrosis. • Normocytic normochromic anemia • Felty's syndrome: RA with splenomegaly and leukopenia • Pul monary disease • Pleural disease (effusions, pleuritis) • I nterstitial l u ng disease (up to 1 Oo/o clin ically sign ificant) • Vascu l itis Cardiac disease • Pericarditis • l Risk cardiovascular disease

•

Ocular disease • Keratoconj unctivitis sicca (dry eye, without d ry mouth/secondary Sjogren's syndrome) ( 1 Oo/o) • Episcleritis, scleritis • Amyloidosis: long-standing RA; can affect heart, kidney, l iver, splee n , i ntestines, and skin

Labs •

•

•

•

•

RF: an i m m u noglobulin d i rected aga i nst the Fe region of the lgG • Sensitivity 20 mg/ day

383

•

•

•

•

•

•

Raynaud's syndrome: • Ca 2 + channel blockers ( i . e . , long-acting d ihydropyrid i nes) • Peri pheral a 1 -adrenergic blockers • Angiotensin II receptor blockers • Pentoxifyl line • Phosphodiesterase i n h i b itors • Stellate ganglionic blockades • Digital sympathectomy Arthralgias: nonsteroidal anti-i nflam matory drugs Ski n : For extensive skin fibrosis, i m m u nomodulatory drugs have been used such as MTX, mycophenolate, and cyclophosphamide but have not been proved to be beneficial . Esophagea l refl ux • H 2 RB • PPis Pulmonary HTN and fibrosis • 02 • Diuretics (with caution) • Endothelin- 1 receptor i n h i bitors (bosenta n , ambrisentan) • Si ldenafi l , tadalafi l • Prostacycl i n analogues (epoprostenol, iloprost, treprostinil) • Lung transplantation • Cyclophosphamide chemoRx for sym ptomatic scleroderma-related interstitial l u ng disease Renal involvement • ACEis • Dialysis • Renal transplantation

I. ENTEROPATHIC ARTHRITIS See Table 1 2-3 . TABLE 1 2-3 • Enteropathlc Arthritis

Feature

Peripheral Arthritis

Sacroiliitis, Spondylitis

1 0%-20% No Transient, symmetric Related to activity of CD Remission of arthritis uncommon Effective

2%-7% Yes Chronic U n related to activity of CD No effect Effective

Frequency in UC H LA-827 associated Pattern Course

5%- 1 0% No Transient More common i n pancolitis than proctitis; related to activity of UC

2%-7% Yes Chronic U n related

Effect of surgery

Remission of arthritis

No effect

Crohn 's Disease {CD]

Frequency i n C D H LA-827 associated Pattern Course Effect of surgery Effect of anti-TNF therapy Ulcerative Colitis {UC]

From Goldman L, Schafer AI (eds): Goldman 's Cecil Medicine, 24th edition. Philadelphia, Saunders, 20 1 2 .

J. CRYSTAL-INDUCED ARTHRITIDES See Table 1 2-4 .

0 COUT Disease characterized by deposition of monosodium u rate crystals i n and about joints, w/subsequent acute or chronic arth ritis Diagnosis H&P

384

•

The typical presentation is monarticular and characterized by sudden severe pai n i nvolving t h e fi rst metatarsophalangeal j o i n t (podagra) . although t h e midtarsal and ankle are also frequently affected ; any joint may be i nvolved, b ut acute polyarthritis is uncommon .

TABLE 1 2-4 • Comparison of Crystal-Induced Arthritides

Crystal-Induced Arthritis

Characteristics of Crystals (from Joint Aspiration)

Gouty arth ritis

Monosodium urate crystals

Ca 2+ pyrophosphate deposition disease (pseudogout)

Ca 2+ pyrophosphate d ihyd rate crystals Rhomboid or polymorphic, weakly positive, birefringent crystals

Hydroxyapatite arthropathy

Ca 2+ hydroxyapatite crystals Crystals form non birefri ngent clumps w/synovial fl uid when placed on slide Dx often requires microscopy because of the small size of the crystals

Knees, h ips, shoulders

Ca 2+ oxalateinduced arthritis

ca 2+ oxalate crystal s Bipyramidal, positive birefringent crystals

D I P , P I P joints of hands

•

-

Commonly Involved Joints

Comments and Therapy

First metatarsophalangeal, ankles, midfoot Knees, wrists

See text

X-ray films of involved joint may reveal linear calcifications (chondrocalcinosis) on articular cartilage Possible associated conditions must be ruled out: Hyperparathyroidism Hypothyroidism Hemochromatosis Hypomagnesemia Therapy: N SAIDs, joint immobilization, intraarticular steroids Usually affects younger pts than the other crystal-induced arthritides do Therapy: N SAIDs, joint immobilization, intraarticular steroids Often seen in pts undergoing dialysis who take large doses of ascorbic acid (metabolized to oxalate) Therapy: N SAIDs, joint im mobilization, intraarticular steroids

PE reveals a warm, tender, swollen, erythematous joint; fever may be present, particularly if several joi nts are involved. Extensive soft tissue swe l l i ng, heat, and erythema extending to above and below the affected joint are frequently present and may be confused w/cellu litis.

Labs • •

Serum uric acid level may be T, but it is often nl duri ng the acute attack, later rising when the sx resolve. Aspiration and analysis of synovial fl uid from the i nflamed joint confirm the dx; exam ination of the fl uid w/a polarized l ight microscope w/compensator reveals monosodium urate crystals (needle-shaped , strongly (-) birefri ngent crystals) w/ synovial fl uid leukocytes.

Treatment • •

•

•

NSAI Ds: PO : indomethaci n , naproxe n , ibuprofen. Ketorolac may be given IM i n N PO pts. Colchicine can be given PO or IV; PO dose is 1 .2 mg fol lowed by a second dose of 0 . 6 mg 1 hr later. IV administration has been associated w/risk of bone marrow suppression and renal or hepatic cell damage. Extravasation can also cause tissue necrosis. Glucocorticoids (triamcinolone acetonide or ACTH) : reserved for pts w/ contraindications to N SAI Ds or colchicine or if PO medication is precluded (e.g. , postop) . Triamcinolone aceton ide, 60 mg I M ; or ACTH , 40 I M or 25 by slow IV i nfusion. I ntra-articular steroids may be used to treat a si ngle inflamed joint (dexamethasone P04- 3 1 -6 mg) . Predn isone 20 to 40 mg PO qd can be used short term i n pts refractory or intolera nt to N SAI Ds/colchicine or responding poorly to these agents.

385

Clinical Pearls •

•

Xanth ine oxidase inhibitors (allopurinol, febuxostat) are used in pts w/frequent recu rrent attacks. Hypouricem ic Rx should not be started for at least 4 wk after the acute attack has resolved because it may prolong the acute attack and can also preci pitate new attacks by rapidly lowering the serum uric acid leve l . Colchicine, 0 . 6 mg P O bid, is indicated for acute gout prophylaxis before hypouricemic Rx is started . It is genera l ly disconti nued 6-8 wk after normalization of serum urate levels. Long-term colchicine Rx (0.6 mg qd or bid) may be necessary in pts w/frequent gout attacks despite the use of uricosuric agents . It can also be used as an alternative to uricosuric agents.

K. IDIOPATHIC INFLAMMATORY

MYOPATHIES See Table 1 2-5 . TABLE 1 2-5 • Classification of the Idiopathic I nflammatory Myopathies

Response of Myositis to Therapy

Prognosis (5-yr Survival)

Variable Mild to moderate Mild

Variable Good

Moderate (-80%) Moderate (-85%)

Excellent

Good [-90%)

Variable

Moderate to poor

Poor, secondary to cancer (-60%)

Variable

Moderate to good

Good (>95%)

Mild but progressive

Poor

Few deaths, but significant morbidity (>85%)

Acute onset i n polymyositis or dermatomyositis I nterstitial lung disease, fever, dyspnea on exertion, arth ritis, mechanic's hands, Raynaud's phenomenon Acute onset in black female pts Palpitations, cardiac disease, severe weakness No rash [clinically polymyositis)

Moderate to severe

Moderate, but flares with taper

Poor (-7 5%)

Severe

Poor

Very poor (-30%)

Classic dermatomyositis "V" and "shawl" rashes, cuticular changes

Mild

Good

Good (>90%)

Classification Croup

Associated Clinical Features

Severity of Myositis

Polymyositis Dermatomyositis

None of the features below Gottron ' s papules or heliotrope rash Overlap with other con nective tissue diseases Cancer diagnosed withi n 2 yr of idiopathic inflammatory myopathy Dx before age 1 8 yr Dermatomyositis » polymyositis Subcutaneous calcifications G l vasculitis Insidious onset in older white men Distal involvement, atrophy, and asymmetric weakness Poor response to therapy

Clinical Groups

Connective tissue myositis Cancer-associated myositis Juvenile myositis

I nclusion body myositis

Serologic Groups

Antisynthetases

Anti-signal recognition particle

Anti-M i-2

From Goldman L, Schafer AI (eds): Goldman 's Cecil Medicine, 24th editio n . Philadelphia, Saunders, 20 1 2 .

386

Interdisciplinary Medicine

13

A. RHABDOMYOLYSIS Acute or subacute event resu lti ng i n damage or necrosis of striated muscle Etiology •

•

•

•

Trauma (e.g . , crush syndrome, burns, electrical shock) M uscle ischemia (e.g. , thrombosis, embol ism , vasculitis, sickle cell disease, pressure necrosis, tou rniquet shock) Drugs: Drug-induced rhabdo can occur th rough several mechanisms. • Primary, toxin induced (e.g. , ethanol , methadone, ethylene glycol , isopropyl alcoho l , CO poisoni ng) • Long-term i ntake of drugs associated w/hypokalemia (e.g . , thiazides) • OD of certai n drugs (e.g. , barbiturates, hero i n , cocaine) • Mal ignant hyperthermia (usually seen i n genetically predisposed individuals, after exposure to halothane, succinylcholine, or pancuronium) • N M S (associated w/use of phenoth iazines, butyrophenones, anti psychotics, cocaine, or diphenhydramine, usually i n pts w/dehydration and electrolyte imbalance) • Use of certai n lipid-lowering agents (e.g. , combi nation of statins and gemfibrozi l , or erythromyci n and simvastati n ; and amiodarone; amphetamines, haloperidol) • Direct myotoxicity (e.g. , colchicine, zidovudine, cyclosporine, itraconazole) Infections • Bacterial (e.g. , Streptococcus, Salmonella, Clostridium, Legionella, Leptospira, Shigella)

• • •

• Vi ral (e.g. , echo, coxsackie, i nfl uenza, CMV, herpes, EBV, hepatitis) • Parasites (trichi nosis) Excessive m uscle stress (e.g. , marathon runners, status epilepticus, delirium tremens) Genetic defects (carnitine deficiency, phosphorylase deficiency, gl ucosidase deficiency, cytochrome disturbances) M iscellaneous: brown recl use spider bite , snake bite , hornet sting, polymyositis, dermatomyositis, heat stroke , DKA, hyponatremia, hypophosphatemia, myxedema, thyroid storm , RMSF, hypothermia, CO, cyclic antidepressants, phenyl propanolamine, codeine, phencyclidine (PCP). amphetam i nes, LSD , Reye 's syndrome

Diagnosis H&.P • •

•

• •

•

•

•

Variable muscle tenderness. Rhabdo apart from statin use is man ifested w/m uscle sx only 50o/o of the time. Weakness M uscle rigidity Fever Altered consciousness M uscle swe l l i ng Malaise, fatigue. I n stati n-ind uced rhabdo, fatigue (74o/o) is nearly as common as muscle pain (88o/o) . Dark urine (secondary to myoglobin in urine, will make di pstick false (+) for RBC's)

Labs

TI CK: Elevations may exceed 1 00, 000 U/L in ful m i nant rhabdo; the development of renal fai l u re is not di rectly related to the threshold level of CK; isoenzyme fractionation is usefu l : if CK- M B >5o/o of the total CK, involvement of the myocardium is l i kely. • TSerum Cr: The etiology of the renal fai l u re is uncerta i n and probably m ultifactorial (renal tubular obstruction by preci pitated myoglobi n , d i rect myoglobin toxicity, hypotension, dehydration, ! GFR, intravascular coagulation) . • Serum K+: Preexisting hypokalemia is a contri buting factor to rhabdo; ful m i nant 387 rhabdo can result in life-th reate n i ng hyperkalemia secondary to T K+ release from damaged muscle and i m paired renal excretio n . •

•

•

Ca 2 + and P04- 3 : I n itially, pts have hyperphosphatemia from muscle necrosis, secondary hypocalcemia from Ca 2 + deposition i n the i njured muscle, and l 1 , 2 5-di hyd roxycholecalciferol ; later (in the d i u retic phase of renal fai l ure) , hypercalcemia is present as a result of remobil ization of the deposited Ca 2 + and secondary hyperparathyroidism. Myoglobin : This is present i n the serum and urine; the urine is brownish , has granular casts, and is 0-toluid ine(+) ; a quick visual method to separate myoglobi nuria from hemoglobi nuria is to examine the urine and serum simultaneously: reddish brown urine and pink serum ind icate hemoglobinuria, whereas brown urine and clear serum suggest myoglobinuria; l i n serum myoglobin precedes the l i n CK level and is useful to esti mate the risk of renal failure (serum myoglobin levels >2000 1-lWL may be associated w/renal insufficiency) .

Treatment •

•

•

•

Vigorous fl uid replacement is given to maintai n a good urinary output, at least until myoglobin disappears from the urine. I n itially N S should be given at a rate of 1 . 5 Uhr w/close mon itori ng of cardiac, pulmonary, and electrolyte status. Maintain l rate of IV fl uids at least until CPK < 1 000 U/L. Pts may require > 1 5 L of fl uid i n the i n itial 24 h r to achieve urine flow rates of 200 to 300 m Uhr. Adm i n i stration of a si ngle dose of mann itol ( 1 00 m l of a 25% solution IV d u ring 1 5 m i n ) remains controversial . M a n n itol acts as an osmotic d i u retic , renal vasodi lator, and i ntravascular vol u m e expander and may convert ol iguric renal fa i l ure to nonoliguric. Alka l i n ization of the urine w/addition of 44 m Eq/L of NaHC0 3 is advocated by some experts. The goal is to maintain urine pH >6. 5 . NaHC0 3 may l sol ubility of uric acid and myoglobul i n ; however, it may promote Ca deposition . Hyperkalemia caused by rhabdo is most severe 1 0 to 40 h r after i nj u ry; i n itial treatment w/sod i u m polystyre ne su lfonate may be i n d i cated ; hyperkalemia caused by rhabdo responds poorly to treatment w/gl ucose and insul i n ; attem pts to correct hyperkalemia and i n itial hypocalcemia w/Ca i nfusion may result i n metastatic calcifications and severe hypercalcemia i n t h e recovery period ; hemodialysis may be necessary i n pts w/severe hyperka l e m i a , vol u m e overload, uremic pericarditis, or u re m i c encephalopathy.

Clinical Pearls • •

The average length of time on stati n Rx before rhabdo is 1 yr. The average time to onset of rhabdo after addition of fib rate to stati n Rx is 32 days. Statin-induced rhabdo is 1 2x more frequent when statins are combined w/fi brates compared w/stati n monoRx.

B. SHOCK •

•

• • •

Figure 1 3- 1 defines shock and its va rious causes. Box 1 3- 1 describes the physical exam and selected lab signs i n shock. Table 1 3- 1 i l l u strates the physiologic response and basic Rx of shock. Figure 1 3-2 is an algorith mic approach to the general hemodynamic management of shock. Table 1 3-2 describes the action of various vasopressor agents used i n shock.

C. HYPOTHERMIA DEFINITION Rectal temperature 65% Scvo2 > 70% Lactate 2.2 Um infm 2 or until Scvo2 > 70% or Svo2 > 65% y Heart rate < 1 00 bpm Shock index ( H RISBP) 60 mUbeat

I

.. Arterial oxygen content y

I Sao2 > 92% 1 � Hemoglobin > 1 0 g/dL

Vo2 1 20-1 40 mUminfm 2

�

I

�

I Demands j-+

System oxygen demands: Stress Pain Hyperthermia Shivering Work of breathing

y

Reversal of organ dysfunction Encephalopathy Liver function tests Renal function FIGURE 1 3-2. General hemodynamic management. Do2, (system) oxygen delivery; PAOP, pulmonary artery occlusion pressure; pHi, intestinal mucosal pH; PPV, pulse pressure variation; SVV, stroke volume variation; Vo2, (systemic) oxygen consumption. (From Goldman L, Schafer AI [ edsj: Goldman's Cecil Medicine, 24th ed. Philadelphia, Saunders, 392 2012.)

TABLE 1 3-2 • Vasopressor Agents

-

Peri�heral Vasculature

Cardiac Eff ects

VasodUation

HR

ContractiUty

Dysritythmlas

0 1 -2+

lt lt

lt 2+

lt 2+

lt 2+

1 1 -20 Jig/kg/m in 0 .04-0. 1 U/min

2-3+ 3-4+

lt 0

2+ 0

2+ 0

3t lt

Phenylephrine

2 0-200 Jlg/min

4t

0

0

0

lt

Norepinephri n e

1 -20 Jig/m i n

4t

0

2+

2+

2+

Epinephrine

1 -20 Jig/m i n

4t

0

4+

4t

4t

Dobutamine

1 -2 0 Jlg/kg/mi n

lt

2+

1 -2+

3+

3t

M il ri none

3 7 . 5-75 Jlg/kg bolus followed by 0 .375-0 . 7 5 11g/mi n

0

2+

lt

3+

2+

Agent

Dose Range

Dopamine

1 -4 Jlg/kg/m in 5-1 0 Jig/kg/mi n

Vasopressin

Vasoconstriction

From Goldman L, Schafer Al (eds) : Goldman's Cecil Medicine, 24th ed. Philadelphia, Saunders , 20 1 2 .

I�

Typical Use "Renal dose" does n ot improve renal fu nction ; may be used with bradycardia and hypotension Vasopressor range Septic shock, post-cardiopul monary bypass shock state; no outcome benefit in sepsis Vasodilatory shock; best for su praventricular tachycardia First -line vasopressor for septic shock, vasodi latory shock Refractory shock, shock with bradycardia, anaphylactic shock cardiogenic shock, septic shock cardiogenic shock, right heart fail ure; dilates pulmonary artery; caution i n renal fai l ure

FIGURE 1 3-3. Hypothermic J waves. (From Ferri F, Practical Guide to the Care of the Medical Patient, 8th ed, St. Louis, Mosby 201 1)

•

•

• • • •

Correct severe acidosis and electrolyte abnlities. Hypothyroidism , if present, should be promptly treated (refer to the section on myxedema coma i n Chapter 5). If c l i n ical evidence suggests adrenal insufficiency, administer IV methylprednisolone. In pts unresponsive to verbal or noxious sti m u l i or w/�MS, 1 00 mg of thiamine, 0 . 4 mg of naloxone, and 1 ampule of 50% dextrose may be give n . Warm ( 1 04° F- 1 1 3° F [40° C-45° C]), humidified 0 2 should a l s o be given if i t is available. Specific treatment: • Mild hypothermia (rectal temperature 2 1 o C [69.8° F]) and cover w/insulating material after gently removing wet cloth i ng; recom mended rewarming rates vary between 0 . 5° C and 20° C/hr but should not exceed 0 . 55° C/h r in elderly pts. • Moderate to severe hypotherm i a : del ivery of heat through fl uids: Methods incl ude warm G l i rrigation (w/sal i n e enemas and by NG tube) , IV fl uids (usually Ds NS w/o K+) warmed to 1 04° F to 1 07 . 6° F (40° C-42° C) . peritoneal dialysis w/dialysate heated to 40 . SO C to 4 2 . SO C , and inhalation of h eated h u m i d ified 02 . Consider i m mersion in a bath of warm water (40° C-4 1 o C) ; active external rewarm i ng may prod uce shock because of excessive peri pheral vasod i lation . Ideal candidates are previously healthy, young pts w/acute i m mersion hypotherm i a . Extracorporeal blood warm ing w/cardiopulmonary bypass appears to be an efficacious rewarming tec h n i q ue i n young, otherwise healthy pts .

D . HEAT STROKE DEFINITION Life-th reatening heat i l lness characterized by extreme hyperthermia, dehydration, and neurologic man ifestations (core temperature >40° C [ 1 04° F]) Diagnosis H&P •

Neurologic manifestations (seizures, tremor, hemi plegia, coma, psychosis, and other bizarre behavior) • Evidence of dehyd ration (poor skin turgor, sunken eyeballs) • Tachycardia, hyperventilation • Hot, red , and fl ushed skin • Sweating often (not always) absent, particularly i n elderly pts

Labs • •

•

•

•

T B U N , Cr, Hct Hyponatremia or hypernatremia, hyperkalemia or hypokalemia T LD H , AST, ALT. CPK, bili Lactic acidosis, respi ratory alkalosis (secondary to hyperventilation) Myoglobinuria, hypofibrinogenemia, fibrinolysis, hypocalcemia

Treatment •

•

394

•

Remove the pt's clothes, and place the pt in a cool and well-ventilated room. If the pt is unconscious, position the pt on his/her side and clear the airway. Protect the airway and augment oxygenation (e.g. , nasal 02 at 4 Um in to keep Sao2 >90%) . Monitor body temperature q 5 m i n . Measurement of the pt's core temperature w/ rectal probe is recommended. Goal is to l the body temperature to 39° C ( 1 02 . 2° F) in 30 to 60 m i n .

• •

• • •

•

• •

Spray the pt w/cool mist, and use fans to enhance ai rflow over the body (rapid evaporation method) . I m mersion o f t h e p t i n i c e water, stomach l avage w/iced sa l i n e soluti o n , IV a d m i n i stration of cooled fl u i d s , and i n h a lation of cold air are advisable only when the means for ra p i d evaporatio n a re not ava i l a b l e . I m mersion i n tepid water ( 1 5° C [ 59° F ] ) i s p referred to ice water i m mersion to m i n i mize risk of sh ivering. Use of ice packs on axi l lae, neck, and groin is controversial because the resulting peri pheral vasoconstriction may induce sh ivering. Anti pyretics are ineffective because the hypothalamic set point during heat stroke is nl despite the body tem perature. Intubate a comatose pt, insert a Foley catheter, and start nasal 0 2 . Conti nuous ECG monitoring is recom mended . Insert at least two large-bore IV l i nes, and begin IV hydration w/N S or lactated Ri nger's solution . Treat compl ications as follows: • Hypotension: Ad m i n i ster vigorous hydration w/NS or lactated Ringer's solution. • Convulsions: G ive diazepam 5 to 1 0 mg IV (slowly) . • Sh ivering: Give chlorpromazi ne 1 0 to 50 mg IV. • Acidosis : Use bicarbonate judiciously (only in severe acidosis) . • Observe for evidence of rhabdo, hepatic, renal , or cardiac fai l u re and treat accordingly.

E . MALIGNANT HYPERTHERMIA DEFI N ITION Muscle rigid ity and elevated temperature i n the setti ng of recently administered anes­ thetic agents, most commonly halogenated inhalation agents (halothane) or depolar­ izing muscle relaxants (succinylcholine) Etiology

In genetically suscepti ble individuals, administration of anesthetic agents results in release of Ca 2 + from the sarcoplasmic reticulum of skeletal m uscles that causes muscle rigidity and hypermetabolism. Th is leads to sign ificant heat production that overwhelms the body's normal abil ity to dissi pate heat. Diagnosis H&P •

•

With i n m i n utes to hours after anesthetic is give n , the pt develops muscle rigid ity (especially masseter spasm). hyperthermia (:545° C), tachycardia that may progress to other dysrhyth mias, and hypotension . Skin i n itially reddens but then becomes cyanotic and mottled. There i s also increased C0 2 production . Rhabdomyolysis, acute renal fai l u re, and D I C may soon fol low.

Labs •

CBC, TS H , electrolytes (especially K+, Ca 2 +, and phosphorus) . PT, PTI , B U N , creat, A LT , AST, a n d CK

Treatment •

•

• •

•

• •

The most i m portant measures for treatment include stopping the anesthetic agents, starting dantrolene, ensuring physical cool i ng, and preventing sequelae. Anti pyretics are not useful because the hypothalamic set point is not altered by cytokines. Cool the pt w/an ice bath , ice packs in the groin and axi llae, cool spray with fa ns, or cooling blankets . I n severe i nstances extracorporeal partial bypass or iced peritoneal lavage may be used . Stop cooling when core temperatu re reaches 38° C to prevent overcooli ng. Carefully monitor the pt's cardiovascular and respiratory status with constant core temperature measurements. Dantrolene i s the mainstay of treatment, starting with a bolus of 5 mg/kg IV, which should be repeated every 5 min until sym ptoms abate or a maxi mum of 1 0 to 20 mg/kg is reached . Then 24 hr of 1 0 mg/kg/day IV should be give n . �-Blockers or l idocaine m a y be useful for dysrhythmias, b u t verapamil should be avoided because its use with dantrolene has been shown to depress cardiac fu nctio n . NaHC0 3 m a y be necessary t o reverse acidosis. Aggressive hydration with forced d i u resis and urine alka l i n ization should be instituted as treatment for rhabdomyolysis.

395

F. NEUROLEPTIC MALIGNANT

SYNDROME (NMS) Disorder characterized by hyperthermia, m uscle rigidity, autonomic dysfunction , and depressed/fl uctuating levels of arousal that evolve d u ring 24 to 7 2 hr Etiology •

Neuroleptic drugs have different potencies for i nducing N M S : • Typical neuroleptics: h igh potency, haloperido l ; medium potency, chlorpromazine, fl uphenazi ne; low potency, levomepromazi ne, loxapine • Atyp ical n e u ro l eptics: l ow pote n cy, risperi d o n e , olanza p i n e , c l oza p i n e , q u eti a p i n e

Diagnosis H&P •

•

•

• • •

Muscle rigidity (hypertonia, cogwheeli ng, or " l ead pipe" rigidity) Hyperthermia (38.6° C-42 . 3° C, usually 7 1 o/o of pts, w/mean value of 3700 U/L) Urinary myoglobin Leukocytosis, usually 1 0,000 to 40,000/mm 3 Electrolytes and renal function ABGs Drug levels

Treatment • •

•

•

•

•

Stop a l l neuroleptic agents, and reinstitute any recently disconti n ued dopaminergic agents. In itiate active cool ing (cooling blanket and anti pyretics) . IV benzos (e.g. , diazepam 2- 1 0 mg, w/total daily dose of 1 0-60 mg) are given to relax m uscles and to control agitation. Bromocri ptine 2.5 to 1 0 mg IV q8h and by 5 mg/day is given until c l i n ical improvement is seen . The drug should be conti nued for � 1 0 days after the syndrome has been control led and then tapered slowly. Dantrolene 0 . 2 5 mg/kg IV q6- 1 2h is followed by a mai ntenance dose up to 3 mg/ kg/day. After 2 to 3 days, pts may be given the drug PO (2 5-600 mg/day in d ivided doses) . Oral dantrolene Rx (50-600 mg/day) may be conti nued for several days afterward . Electroconvulsive Rx w/neuromuscular blockage is indicated i n pharmacologically refractory cases. Succi nylchol i n e should not be used because it may cause hyperkalemia and cardiac arrhythmias i n pts w/rhabdo or dysautonom ia.

G. ANAPHYLAXIS Sudden-onset, l ife-th reaten i ng event characterized by respiratory, cardiovascular, G l , and cutaneous man ifestations, a s wel l a s vasodilatory hemodynam i c changes i n re­ sponse to a particular allergen Etiology •

• • •

•

•

Caused by sudden systematic release of h i stamine and other i nflammatory mediators from basophils and mast cells � swe l l i ng of the mucous membranes and u rticarial rash on the ski n . Vi rtual ly any substance may i nduce anaphylaxis. Foods and food add itives: pean uts , tree n uts, eggs, shellfish , fi s h , cow ' s m i l k, fruits, soy Medications: antibiotics, especially pen icill ins, insu l i n , allergen extracts , opiates, vacci nes, N SAIDs, contrast media, streptokinase Bee or wasp sti ng, snake venom, fire ant venom Blood products, plasma, i m m unoglobul i n , cryoprecipitate , whole blood Latex

Diagnosis

396 H&P • Urticaria, pruritus, skin flushing, angioedema • Dyspnea , cough , wheezing, shortness of breath

•

•

Nausea, vom iting, d iarrhea, d ifficulty swal lowing Hypotension, tachycardia, weakness, dizzi ness, malaise, vascular collapse

Differential Diagnosis •

• •

•

• •

•

Endocri ne disorders (carcinoid, pheoch romocytoma) Globus hystericus, anxiety disorder Systemic mastocytosis PE, serum sickness, vasovagal reactions Severe asth ma (the key c l i n ical d ifference is the abrupt onset of symptoms in anaphylaxis versus a history of progressive worse n i ng of sym ptoms) Septic shock or other form of vasodi latory shock Ai rway foreign body

Labs •

•

•

Generally tests are not hel pfu l because anaphylaxis is typica l ly diagnosed clinica l ly. ABC analysis may be useful to exclude PE, status asthmaticus, and foreign body aspiration. T Serum and urine histamine levels and serum tryptase levels can be useful for dx of anaphylaxis, but these tests are not commonly avai lable in the emergency setting.

Imaging •

• •

Imaging is generally not helpfu l . CXRs for eval uation o f foreign body aspiration or pul monary disease are indicated in pts with acute respi ratory compromise. Consider ECG i n all pts with sudden loss of consciousness, chest pai n , dyspnea and in any elderly pt. ECG i n anaphylaxis usually reveals sinus tachycardia.

Treatment •

•

•

•

•

•

• •

Establish and protect the a i rway. Provide supplemental 0 2 if indicated. IV access should be rapidly established, and IV fl uids ( i . e . , N S) should be admin istered . The pt should be placed supine or i n Trendelenburg's position if hemodynamically unstable. Cardiac mon itoring is recommended. Epinephrine: IM i njection at a dose of 0.3 mg of aqueous epinephrine for adults and chi ldren >30 kg. Epinephrine 0 . 1 5 mg should be given for chi ldren