Kirk's Current Veterinary Therapy XIV [1, 14 ed.] 9780721694979

Citation preview

:.To access your free online resources, visit: http://evolve.elsevier.com/Bonagura/Kirks/ Evolve® Online Courseware for Bonagura/Twedt: Current Veterinary Therapy XIV, offers the following features:

Resources • • • • • •

Selected chapters from CVT XIII Fully searchable index Drug formulary References linked to Pub Med Other helpful appendices Image collection

http://evolve.elsevier.com/Bonagura/Kirks/

Editor

John D. Bonagura, DVM, MS, DACVIM (Cardiology, Internal Medicine) Professor Department of Veterinary Clinical Sciences College of Veterinary Medicine The Ohio State University Columbus, Ohio

Associate Editor

David C. Twedt, DVM, DACVIM (Internal Medicine) Professor Department of Clinical Sciences College of Veterinary Medicine and Biomedical Sciences Colorado State University Fort Collins, Colorado with more than 325 illustrations

11830 Westline Industrial Drive St. Louis, Missouri 63146 KIRK’S CURRENT VETERINARY THERAPY XIV

ISBN 978-0-7216-9497-9

Copyright © 2009, 2000, 1995, 1992, 1989, 1986, 1983, 1980, 1977, 1974, 1971, 1968, 1966, 1964 by Saunders, an imprint of Elsevier Inc. All rights reserved. No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopying, recording, or any information storage and retrieval system, without permission in writing from the publisher. Permissions may be sought directly from Elsevier’s Rights Department: phone: (+1) 215 239 3804 (US) or (+44) 1865 843830 (UK); fax: (+44) 1865 853333; e-mail: [email protected]. You may also complete your request on-line via the Elsevier website at http://www.elsevier.com/permissions.

Notice Knowledge and best practice in this field are constantly changing. As new research and experience broaden our knowledge, changes in practice, treatment and drug therapy may become necessary or appropriate. Readers are advised to check the most current information provided (i) on procedures featured or (ii) by the manufacturer of each product to be administered, to verify the recommended dose or formula, the method and duration of administration, and contraindications. It is the responsibility of practitioners, relying on their own experience and knowledge of the patient, to make diagnoses, to determine dosages and the best treatment for each individual patient, and to take all appropriate safety precautions. To the fullest extent of the law, neither the Publisher nor the Editors assumes any liability for any injury and/or damage to persons or property arising out of or related to any use of the material ­contained in this book. The Publisher

ISBN 978-0-7216-9497-9 Vice President and Publisher: Linda Duncan Publisher: Penny Rudolph Managing Editor: Jolynn Gower Publishing Services Manager: Pat Joiner-Myers Senior Project Manager: Karen M. Rehwinkel Designers: Julia Dummitt, Charles J. Seibel

Printed in the United States of America Last digit is the print number: 9 8 7 6 5 4 3 2 1

Consulting Editors SECTION I  Critical Care

SECTION VIII  Cardiovascular Diseases

Nishi Dhupa, BVM, DACVIM (Internal Medicine), DACVECC

John D. Bonagura, DVM, MS, DACVIM (Cardiology, Internal Medicine)

SECTION II  TOXICOLOGIC DISEASES

SECTION IX Urinary Diseases

Michael J. Murphy, DVM, PhD, DACT

India F. Lane, DVM, MS, DACVIM

SECTION III Endocrine and Metabolic DisEASES

SECTION X Reproductive Diseases

Mark E. Peterson, DVM, DACVIM SECTION IV  ONCOLOGY AND HEMATOLOGY

Douglas H. Thamm, VMD, DACVIM (Oncology)

Margaret V. Root Kustritz, DVM, PhD, DACT SECTION XI Neurologic and Musculoskeletal Diseases

Rodney S. Bagley, DVM, DACVIM (Neurology, Internal Medicine)

SECTION V  Dermatologic Diseases

Craig E. Griffin, DVM, DACVD Wayne S. Rosenkrantz, DVM, DACVD

SECTION XII  OphthalmIC Diseases

SECTION VI  Gastrointestinal Diseases

SECTION XIII  Infectious Diseases

David C. Twedt, DVM, DACVIM (Internal Medicine)

Rance K. Sellon, DVM, PhD, DACVIM

David J. Maggs, BVSc, DACVO

SECTION VII Respiratory Diseases

Appendix I Table of Common Drugs: Approximate Dosages

Eleanor C. Hawkins, DVM, DACVIM

Mark G. Papich, DVM, MS, DACVCP



This page intentionally left blank

Contributors Jonathan A. Abbott, DVM

Verena K. Affolter, DVM, PhD

Associate Professor of Cardiology Department of Small Animal Clinical Sciences Virginia-Maryland Regional College of Veterinary Medicine Virginia Polytechnic Institute and State University Blacksburg, Virginia Subaortic Stenosis

Associate Professor for Clinical Dermatopathology Department of Pathology, Microbiology, and Immunology School of Veterinary Medicine University of California Davis, California Histiocytic Disease Complex Nonneoplastic Nodular Histiocytic Diseases of the Skin

Mark J. Acierno, DVM, DACVIM Assistant Professor School of Veterinary Medicine The Louisiana State University Baton Rouge, Louisiana Systemic Hypertension in Renal Disease

Larry G. Adams, DVM, PhD, DACVIM (SAIM) Associate Professor, Small Animal Internal Medicine Department of Veterinary Clinical Sciences Purdue University West Lafayette, Indiana Laser Lithotripsy for Uroliths

Diane D. Addie, PhD, BVMS, MRCVS Feline Institute Pyrenees Etchebar, France; Honorary Senior Research Fellow Institute of Comparative Medicine University of Glasgow Veterinary School Glasgow, Scotland United Kingdom Control of Viral Diseases in Catteries Feline Infectious Peritonitis: Therapy and Prevention

Christopher A. Adin, DVM, DACVS Courtesy Faculty Appointment Small Animal Clinical Sciences College of Veterinary Medicine University of Florida Gainesville, Florida; Small Animal Surgeon Veterinary Specialists of Rochester Rochester, New York Renal Transplantation

Darcy B. Adin, DVM, DACVIM (Cardiology) Veterinary Specialists of Rochester Rochester, New York Tricuspid Valve Dysplasia

P. Jane Armstrong, DVM, MS, MBA, DACVIM (SAIM) Professor, Internal Medicine/Clinical Nutrition Department of Veterinary Clinical Sciences College of Veterinary Medicine University of Minnesota St. Paul, Minnesota Feline Inflammatory Liver Disease

Clarke E. Atkins, DVM, DACVIM (Internal Medicine, Cardiology) Professor of Medicine and Cardiology Veterinary Teaching Hospital College of Veterinary Medicine North Carolina State University Raleigh, North Carolina Feline Heartworm Disease

Anne Avery, VMD, PhD Assistant Professor Director Clinical Immunopathology Service Department of Microbiology, Immunology, and Pathology College of Veterinary Medicine and Biomedical Sciences Colorado State University Fort Collins, Colorado Canine Lymphoma

Sandra M. Axiak, DVM Veterinary Specialists of North Texas and Animal Care Center Dallas, Texas Pulmonary Neoplasia

Todd W. Axlund, DVM, MS, DACVIM (Neurology) Director Metropolitan Veterinary Hospital Akron, Ohio Treatment of Intracranial Tumors

vii

viii

Contributors

Rodney S. Bagley, DVM, DACVIM (Neurology, Internal Medicine) Professor, Neurology and Neurosurgery Department of Veterinary Clinical Sciences Washington State University Pullman, Washington Treatment of Canine Cervical Spondylomyelopathy: A Critical Review Treatment of Degenerative Lumbosacral Stenosis Vestibular Disease of Dogs and Cats

Claudia J. Baldwin, DVM, MS, DACVIM (Internal Medicine) Associate Professor, Veterinary Clinical Sciences College of Veterinary Medicine Iowa State University Ames, Iowa Pregnancy Loss in the Queen

Tania A. Banks, BVSc, FACVSc Brisbane Veterinary Specialist Centre Albany Creek, Queensland Australia Canine Soft-Tissue Sarcomas

Jeanne A. Barsanti, DVM, MS, DACVIM (SAIM) Josiah Meigs Distinguished Teaching Professor Department of Small Animal Medicine and Surgery College of Veterinary Medicine The University of Georgia Athens, Georgia Multidrug-Resistant Urinary Tract Infection

Joseph W. Bartges, DVM, PhD, DACVIM, DACVN Professor of Medicine and Nutrition The Acree Endowed Chair of Small Animal Research Department of Small Animal Clinical Sciences College of Veterinary Medicine The University of Tennessee Knoxville, Tennessee Interpreting and Managing Crystalluria

Shane W. Bateman, DVM, DVSC, DACVECC Associate Professor, Clinical Department of Veterinary Clinical Sciences College of Veterinary Medicine The Ohio State University Columbus, Ohio Fluid Therapy Ventilator Therapy

Karin M. Beale, DVM, DACVD Staff Dermatologist Gulf Coast Veterinary Dermatology & Allergy Houston, Texas Feline Demodicosis

Ellen N. Behrend, DVM, DACVIM Associate Professor Department of Clinical Sciences College of Veterinary Medicine Auburn University Auburn, Alabama Interpretation of Endocrine Diagnostic Test Results for Adrenal and Thyroid Disease

Adrienne Bentley, DVM Resident in Surgery School of Veterinary Medicine University of Pennsylvania Philadelphia, Pennsylvania Drainage Techniques for the Septic Abdomen

Ellison Bentley, DVM, DACVO Clinical Associate Professor Comparative Ophthalmology Department of Surgical Sciences School of Veterinary Medicine University of Wisconsin Madison, Wisconsin Nonhealing Corneal Erosions in Dogs

Allyson C. Berent, DVM, DACVIM Staff Veterinarian in Small Animal Internal Medicine and Interventional Radiology Waltham Lecturer: Minimally Invasive Diagnostics/ Therapeutics Matthew J. Ryan Veterinary Teaching Hospital School of Veterinary Medicine University of Pennsylvania Philadelphia, Pennsylvania Interventional Radiology in Urinary Diseases

Philip J. Bergman, DVM, MS, PhD, DACVIM (Oncology) Chief Medical Officer Bright Heart Veterinary Centers Armonk, New York Malignant Melanoma

Adam J. Birkenheuer, DVM, DACVIM (Internal Medicine) Assistant Professor of Internal Medicine Department of Clinical Sciences College of Veterinary Medicine North Carolina State University Raleigh, North Carolina Babesiosis Thrombocytopenia

Karyn Bischoff, DVM, MS, DABVT Diagnostic Toxicologist Animal Health Diagnostic Center Assistant Professor College of Veterinary Medicine Cornell University Ithaca, New York Aflatoxicosis in Dogs Automotive Toxins

Dana R. Bleifer, DVM Warner Center Pet Clinic Woodland Hills, California False Pregnancy in the Bitch



Contributors

John D. Bonagura, DVM, MS, DACVIM (Cardiology, Internal Medicine)

Amanda Burrows, BSc, BVMS, FACVSc (Veterinary Dermatology)

Professor Department of Veterinary Clinical Sciences College of Veterinary Medicine The Ohio State University Columbus, Ohio Management of Heart Failure in Dogs Ventricular Septal Defect

Veterinary Hospital Murdoch University Murdoch Western Australia Avermectins in Dermatology

Dino M. Bradley, DVM, MS Research Associate Scott-Ritchey Research Center College of Veterinary Medicine Auburn University Auburn, Alabama Acral Lick Dermatitis

Edward B. Breitschwerdt, DVM, DACVIM Professor of Medicine and Infectious Diseases Director, NCSU-CVM Biosafety Laboratory Adjunct Associate Professor of Medicine Duke University Medical Center Department of Clinical Sciences College of Veterinary Medicine North Carolina State University Raleigh, North Carolina Bartonellosis

Janice M. Bright, BSN, MS, DVM, DACVIM (Internal Medicine, Cardiology) Professor of Cardiology Department of Clinical Sciences College of Veterinary Medicine and Biomedical Sciences Colorado State University Fort Collins, Colorado Cardioversion

Marjory B. Brooks, DVM, DACVIM

ix

Julie K. Byron, DVM, MS, DACVIM Assistant Professor, Small Animal Medicine Department of Clinical Medicine University of Illinois at Urbana-Champaign Urbana, Illinois Urinary Incontinence: Treatment With Injectable Bulking Agents

Clay A. Calvert, DVM, DACVIM (Internal Medicine) Professor Department of Small Animal Medicine College of Veterinary Medicine University of Georgia Athens, Georgia Cardiomyopathy in Doberman Pinschers Syncope

Anthony P. Carr, DrMedVet, DACIM Associate Professor Western College of Veterinary Medicine University of Saskatchewan Saskatoon, Saskatchewan Canada von Willebrand’s Disease and Other Hereditary Coagulopathies

Elizabeth W. Carsten, DVM, DACVIM Internal Medicine Consultant IDEXX Laboratories, Inc. Oro Valley, Arizona Esophagitis

Associate Director, Comparative Coagulation Laboratory Department of Population Medicine and Diagnostic Sciences College of Veterinary Medicine Cornell University Ithaca, New York Antiplatelet and Anticoagulant Therapy Platelet Dysfunction

James L. Catalfamo, MS, PhD

Cathy A. Brown, VMD, PhD, DACVP

Daniel L. Chan, DVM, MRCVS, DACVECC, DACVN

Professor, Pathology Athens Diagnostic Laboratory College of Veterinary Medicine University of Georgia Athens, Georgia Glomerular Disease

Barret J. Bulmer, DVM, MS, DACVIM (Cardiology) Assistant Professor Veterinary Clinical Sciences College of Veterinary Medicine Oregon State University Corvallis, Oregon Mitral Valve Dysplasia

Director, Comparative Coagulation Laboratory Department of Population Medicine and Diagnostic Sciences College of Veterinary Medicine Cornell University Ithaca, New York Platelet Dysfunction Lecturer in Emergency and Critical Care Department of Veterinary Clinical Sciences The Royal Veterinary College University of London London, England United Kingdom Nutrition in Critical Care

Annie V. Chen, DVM Department of Veterinary Clinical Sciences College of Veterinary Medicine Washington State University Pullman, Washington Treatment of Canine Cervical Spondylomyelopathy: A Critical Review



Contributors

Dennis J. Chew, DVM, DACVIM (Internal Medicine) Professor College of Veterinary Medicine The Ohio State University Columbus, Ohio Idiopathic Feline Hypercalcemia Treatment of Hypoparathyroidism Urinary Incontinence: Treatment With Injectable Bulking Agents

Ruthanne Chun, DVM, DACVIM (Oncology) Clinical Associate Professor Member, University of Wisconsin Comprehensive Cancer Center School of Veterinary Medicine University of Wisconsin Madison, Wisconsin Anal Sac Tumors

Julie Churchill, DVM, PhD Assistant Clinical Professor Veterinary Clinical Sciences College of Veterinary Medicine University of Minnesota St. Paul, Minnesota Food Toxicoses in Small Animals

Craig A. Clifford, DVM, MS, DACVIM (Oncology) Staff Oncologist Red Bank Veterinary Hospital Tinton Falls, New Jersey Canine Hemangiosarcoma

Joan R. Coates, DVM, MS, DACVIM (Neurology) Associate Professor Veterinary Medicine and Surgery Neurology/Neurosurgery Service Leader Veterinary Medical Teaching Hospital Department of Veterinary Medicine and Surgery College of Veterinary Medicine University of Missouri Columbia, Missouri Treatment of Animals With Spinal and Musculoskeletal Pain

Leah A. Cohn, DVM, PhD, DACVIM (SAIM) Associate Professor of Veterinary Internal Medicine Department of Veterinary Medicine and Surgery College of Veterinary Medicine University of Missouri Columbia, Missouri Canine Anaplasma Infection

Lynette K. Cole, DVM, MS, DACVD Assistant Professor Department of Veterinary Clinical Sciences College of Veterinary Medicine The Ohio State University Columbus, Ohio Systemic Therapy for Otitis Externa and Media

Patrick Concannon, MS, PhD, DACT (Honorary) Visiting Fellow, Department of Clinical Sciences Director Laboratory for Comparative Reproduction Studies Department of Biomedical Sciences College of Veterinary Medicine Cornell University Ithaca, New York Estrus Suppression in the Bitch

Gheorge M. Constantinescu, DVM, PhD, Drhc Professor of Veterinary Anatomy College of Veterinary Medicine University of Missouri Columbia, Missouri Brachycephalic Upper Airway Syndrome in Dogs

Johanna C. Cooper, BSc, DVM, DACVIM Cape Cod Veterinary Specialists Buzzards Bay, Massachusetts Diagnostic Approach to Hepatobiliary Disease

Brendan M. Corcoran, MVB, DipPharm, PhD, MRCVS Senior Lecturer Hospital for Small Animals Division of Veterinary Clinical Studies The University of Edinburgh Easterbush Veterinary Centre Edinburgh, Scotland United Kingdom Interstitial Lung Diseases

Etienne Côté, DVM, DACVIM (Cardiology, SAIM) Assistant Professor Department of Companion Animals Atlantic Veterinary College University of Prince Edward Island Charlottetown, Prince Edward Island Canada Feline Cardiac Arrhythmias

Nancy B. Cottrill, DVM, MS, DACVO Staff Ophthalmologist Angell Animal Medical Center, Western New England Woburn, Massachusetts Differential Diagnosis of Anisocoria

Dennis T. Crowe, Jr., DVM, NREMT-I, PI, CFF, DACVS, DACVECC President Veterinary Surgery, Emergency and Critical Care Services and Consulting Bogart, Georgia Oxygen Therapy

Autumn P. Davidson, DVM, MS, DACVIM (Internal Medicine) Clinical Professor School of Veterinary Medicine University of California Davis, California Canine Brucellosis Dystocia Management



Contributors

Thomas K. Day, DVM, MS, DACVECC, DACVA

Stephen P. DiBartola, DVM, DACVIM (SAIM)

Owner Louisville Veterinary Specialty & Emergency Services Louisville, Kentucky Intravenous Anesthetic and Analgesic Techniques

Professor Department of Veterinary Clinical Sciences College of Veterinary Medicine The Ohio State University Columbus, Ohio Acid-Base Disorders Fluid Therapy

Douglas J. DeBoer, DVM, DACVD Professor Department of Medical Sciences School of Veterinary Medicine University of Wisconsin Madison, Wisconsin Treatment of Dermatophytosis

Patricia M. Dowling, DVM, MSc, DACVIM, DACVCP

Shoreline Veterinary Dental Clinic Seattle, Washington Feline Caudal Stomatitis

Professor, Veterinary Clinical Pharmacology Western College of Veterinary Medicine University of Saskatchewan Veterinary Biomedical Sciences Saskatoon, Saskatchewan Canada Rational Empiric Antimicrobial Therapy

Louis-Philippe de Lorimier, DVM, DACVIM (Oncology)

Kenneth J. Drobatz, DVM, MS, DACVIM, DACVECC

Linda J. DeBowes, DVM, MS, DACVIM, DAVDC

Staff Medical Oncologist Hôpital Vétérinaire Rive-Sud Brossard, Québec Canada Canine Hemangiosarcoma

Helio Autran de Morais, DVM, PhD, DACVIM (SAIM, Cardiology) Clinical Associate Professor Department of Medical Sciences University of Wisconsin Madison, Wisconsin Acid-Base Disorders

Robert C. DeNovo, DVM, MS, DACVIM Professor and Head Department of Small Animal Clinical Sciences College of Veterinary Medicine University of Tennessee Knoxville, Tennessee Canine Megaesophagus

Curtis W. Dewey, DVM, MS, DACVIM (Neurology), DACVS Associate Professor, Neurology/Neurosurgery Neurology/Neurosurgery Service Chief Cornell University Hospital for Animals Cornell University Ithaca, New York New Maintenance Anticonvulsant Therapies for Dogs and Cats Traumatic Brain Injury Treatment of Canine Chiari-Like Malformation and Syringomyelia

xi

Director of the Emergency Service Chief of Critical Care Section Matthew J. Ryan Veterinary Hospital School of Veterinary Medicine University of Pennsylvania Philadelphia, Pennsylvania Noncardiogenic Pulmonary Edema Urethral Obstruction in Cats

†Robert B. Duncan, DVM, PhD, DACVP Associate Professor, Pathology Department of Pathobiology and Biomedical Sciences Virginia-Maryland Regional College of Veterinary Medicine Virginia Polytechnic Institute and State University Blacksburg, Virginia Gastric Helicobacter spp. and Chronic Vomiting in Dogs

Marilyn Dunn, DMV, MVSc, DACVIM (SAIM) Assistant Professor Clinical Sciences University of Montreal Small Animal Clinic Faculty of Veterinary Medicine University of Montreal Saint-Hyacinthe, Quebec Canada Antiplatelet and Anticoagulant Therapy

Anna R. Deykin, BSc, BVMS, FACVSc (Ophthalmology) Veterinary Ophthalmologist Brisbane Veterinary Specialist Centre Brisbane, Queensland Australia Episcleritis and Scleritis in Dogs †Deceased.

xii

Contributors

David A. Dzanis, DVM, PhD, DACVN

James P. Farese, DVM, DACVS

Owner Dzanis Consulting & Collaborations Santa Clarita, California Nutrition in the Bitch During Pregnancy and Lactation Appendix III: AAFCO Dog and Cat Food Nutrient Profiles

Associate Professor, Surgical Oncology Small Animal Clinical Sciences College of Veterinary Medicine University of Florida Gainesville, Florida Surgical Oncology Principles

Nicole P. Ehrhart, VMD, DACVS Associate Professor Department of Clinical Sciences College of Veterinary Medicine and Biomedical Sciences Colorado State University Fort Collins, Colorado Osteosarcoma

Bruce E. Eilts, DVM, MS, DACT Professor of Theriogenology Department of Veterinary Clinical Sciences School of Veterinary Medicine Louisiana State University Baton Rouge, Louisiana Canine Pregnancy Termination

Denise A. Elliott, BVSc (Hons), PhD, DACVIM, DACVN Director of Scientific Affairs Royal Canin St. Charles, Missouri Gastrostomy Tube Feeding in Kidney Disease

Jonathan Elliott, MA, Vet MB, PhD, Cert SAC, DECVPT, MRCVS Department of Veterinary Basic Sciences Royal Veterinary College University of London London, England United Kingdom Chronic Kidney Disease: Staging and Management

Gary C.W. England, BVetMed, PhD, DVR, DVRep, DECAR, DACT, ILTM, FRCVS Foundation Dean School of Veterinary Medicine and Science University of Nottingham Nottingham, England United Kingdom Breeding Management of the Bitch

Amara Estrada, DVM, DACVIM (Cardiology) Assistant Professor Small Animal Clinical Sciences College of Veterinary Medicine University of Florida Gainesville, Florida Pulmonic Stenosis

Timothy M. Fan, DVM, DACVIM Assistant Professor, Medical Oncology Veterinary Clinical Medicine University of Illinois at Urbana-Champaign Urbana, Illinois Osteosarcoma

Edward C. Feldman, DVM, DACVIM Professor Department of Medicine and Epidemiology School of Veterinary Medicine University of California Davis, California Canine Hypercalcemia and Primary Hyperparathyroidism

Deborah M. Fine, DVM, MS, DACVIM (Cardiology) Assistant Professor Department of Veterinary Medicine and Surgery University of Missouri Columbia, Missouri Arterial Thromboembolism in Cats

Bente Flatland, DVM, MS, DACVIM (Internal Medicine) Resident, Clinical Pathology Department of Pathobiology College of Veterinary Medicine University of Tennessee Knoxville, Tennessee Hepatic Support Therapy

Daniel J. Fletcher, DVM, PhD, DACVECC Lecturer, Emergency and Critical Care Cornell University Hospital for Animals Cornell University Ithaca, New York Traumatic Brain Injury

Richard B. Ford, DVM, MS, DACVIM Professor of Medicine College of Veterinary Medicine North Carolina State University Raleigh, North Carolina Bacterial Pneumonia Bordetella bronchiseptica: Beyond Kennel Cough Canine Vaccination Guidelines Feline Vaccination Guidelines

Lisa J. Forrest, VMD, DACVR Associate Professor Surgical Sciences University of Wisconsin Madison, Wisconsin Nasal Tumors



Contributors

Theresa W. Fossum, DVM, MS, PhD, DACVS

Tam Garland, DVM

Tom and Joan Read Chair in Veterinary Surgery Associate Director Cardiothoracic Surgery and Biomedical Devices, Michael E. DeBakey Institute Professor of Surgery College of Veterinary Medicine Texas A&M University College Station, Texas Pleural Effusion

Program Manager for Agricultural Security Director for the Joint Agro Defense Office Science and Technology Directorate Department of Homeland Security Washington, District of Columbia Aflatoxicosis in Dogs

Susan F. Foster, BVSc, MVetClinStud, FACVSc, (Feline Medicine)

European Specialist in Veterinary Neurology Neurology/Neurosurgery Service Head Davies Veterinary Specialists Manor Farm Business Park Higham Gobion, England United Kingdom Treatment of Cerebrovascular Disease

Adjunct Senior Lecturer in Small Animal Medicine Murdoch University Murdoch, Australia Nasopharyngeal Disorders

Philip R. Fox, DVM, MSc, DACVIM (Cardiology), DACVECC

Laurent S. Garosi, DVM, MRCVS, DECVN, RCVS

Anthony T. Gary, DVM, DACVIM

Cardiologist Bobst Hospital of the Animal Medical Center Director, Caspary Research Institute The Animal Medical Center New York, New York Right Ventricular Cardiomyopathy in Cats

Arkansas Veterinary Internal Medicine North Little Rock, Arkansas Evaluation of Elevated Serum Alkaline Phosphatase in the Dog

Boel A. Fransson, DVM, MSc, PhD, DACVS

Assistant Professor of Veterinary Cardiology College of Veterinary Medicine Cornell University Ithaca, New York Pacing in the Critical Care Setting Ventricular Arrhythmias in Dogs

Assistant Professor, Small Animal Surgery Department of Veterinary Clinical Sciences Washington State University Pullman, Washington Treatment of Supraspinatus Tendon Disorders in Dogs

Lisa M. Freeman, DVM, PhD, DACVN Associate Professor Department of Clinical Sciences Cummings School of Veterinary Medicine Tufts University North Grafton, Massachusetts Nutritional Management of Heart Disease

Joni L. Freshman, DVM, MS, DACVIM Owner Canine Consultations Colorado Springs, Colorado Pregnancy Loss in the Bitch

Angela E. Frimberger, VMD, DACVIM (Oncology) Director, Veterinary Oncology Consultants Wauchope, New South Wales Australia Anticancer Drugs and Protocols: Traditional Drugs

Virginia Luis Fuentes, MA VetMB, PhD, CertVR, DVC, MRCVS, DACVIM (Cardiology), DECVIM (Cardiology) Senior Lecturer Veterinary Clinical Sciences Royal Veterinary College Hatfield, Hertfordshire United Kingdom Management of Feline Myocardial Disease

xiii

Anna R.M. Gelzer, Dr Med Vet, DACVIM (Cardiology), DECVIM (Cardiology)

Alexander J. German, BVSc, PhD, DECVIM-CA (Internal Medicine) Senior Lecturer, Department of Veterinary Clinical Sciences Small Animal Hospital The University of Liverpool Liverpool, England United Kingdom Inflammatory Bowel Disease

Rudayna Ghubash, DVM, DACVD Staff Dermatologist Animal Dermatology Clinic Marina del Rey, California Feline Viral Skin Disease

Urs Giger, PD, Dr Med Vet, MS, FVH, DACVIM, DECVIM, DECVCP Charlotte Newton Sheppard Professor of Medicine Chief of Medical Genetics Department of Clinical Studies School of Veterinary Medicine University of Pennsylvania Philadelphia, Pennsylvania Blood-Typing and Crossmatching

Sophie Gilbert, DVM, PhD, DACVD New York City Veterinary Specialists New York, New York Feline Pruritus Therapy

xiv

Contributors

Rebecca E. Gompf, DVM, MS, DACVIM (Cardiology) Associate Professor Small Animal Clinical Sciences College of Veterinary Medicine University of Tennessee Knoxville, Tennessee Ventricular Septal Defect

Jody L. Gookin, DVM, PhD, DACVIM (Internal Medicine) Assistant Professor, Molecular Biomedical Sciences College of Veterinary Medicine North Carolina State University Raleigh, North Carolina Tritrichicomonas

Sonya G. Gordon, DVM, DVSc, DACVIM (Cardiology) Assistant Professor Department of Small Animal Clinical Sciences College of Veterinary Medicine and Biomedical Sciences Texas A&M University College Station, Texas Canine Heartworm Disease Patent Ductus Arteriosus

Gregory F. Grauer, DVM, MS, DACVIM (Internal Medicine) Professor Department of Clinical Sciences Kansas State University Manhattan, Kansas Proteinuria: Implications for Management

Clare R. Gregory, DVM, DACVS Professor Department of Surgical and Radiological Sciences Director, Comparative Transplantation Laboratory School of Veterinary Medicine University of California Davis, California Immunosuppressive Agents

Joel D. Griffies, DVM, DACVD Animal Dermatology Clinic Tustin, California Topical Immunomodulators

Craig E. Griffin, DVM, DACVD Animal Dermatology Clinic and Animal Allergy Specialists San Diego, California Allergen-Specific Immunotherapy Cyclosporine Use in Dermatology

Carol B. Grindem, DVM, DACVP (Clinical Pathology) Professor College of Veterinary Medicine North Carolina State University Raleigh, North Carolina Thrombocytopenia

Amy M. Grooters, DVM, DACVIM (SAIM)

Nestle Purina Petcare St. Louis, Missouri Complicated Diabetes Mellitus

Associate Professor and Chief Companion Animal Medicine Veterinary Clinical Sciences Louisiana State University; Chief of Staff Small Animal Clinic Veterinary Teaching Hospital Baton Rouge, Louisiana Pythiosis and Lagenidiosis

Eric M. Green, DVM, DACVR (Radiology, Radiation Oncology)

Sharon M. Gwaltney-Brant, DVM, PhD, DABVT, DABT

Associate Professor Veterinary Clinical Sciences College of Veterinary Medicine The Ohio State University Columbus, Ohio Radiotherapy: Basic Principles and Indications

ASPCA Animal Poison Control Center Urbana, Illinois Lead Toxicosis in Small Animals Recently Recognized Animal Toxicants

Henry W. Green, III, DVM, DACVIM (Cardiology)

Department Chair Critical Care and Emergency Services The Animal Medical Center New York, New York Pulmonary Thromboembolism

Deborah S. Greco, DVM, PhD, DACVIM

Assistant Professor, Cardiology Veterinary Clinical Sciences School of Veterinary Medicine Purdue University West Lafayette, Indiana Dilated Cardiomyopathy in Dogs

Susan G. Hackner, BVSc, MRCVS, DACVIM, DACVECC

Kevin A. Hahn, DVM, PhD, DACVIM (Oncology) Gulf Coast Veterinary Specialists Houston, Texas Pulmonary Neoplasia



Contributors

Kelly Hall, DVM

Mattie J. Hendrick, VMD, DACVP

Assistant Clinical Professor Veterinary Clinical Sciences University of Minnesota St. Paul, Minnesota Toxicosis Treatments Toxin Exposures and Treatments: A Survey of Practicing Veterinarians

Staff Pathologist and Adjunct Full Professor of Pathology School of Veterinary Medicine University of Pennsylvania Philadelphia, Pennsylvania Feline Vaccine-Associated Sarcomas

Holly L. Hamilton, DVM, MS, DACVO

Associate Professor, Ophthalmology Department of Small Animal Clinical Sciences College of Veterinary Medicine University of Tennessee Knoxville, Tennessee Differential Diagnosis of the Red Eye

Ophthalmologist Animal Eye Center Loveland, Colorado Differential Diagnosis of Blindness

William R. Hare, DVM, MS, PhD, DABVT, DABT Veterinary Medical Officer United States Department of Agriculture Agricultural Research Service Animal and Natural Resources Institute Beltsville Agricultural Research Center Beltsville, Maryland Urban Legends of Toxicology: Facts and Fiction

Kenneth R. Harkin, DVM, DACVIM (SAIM) Associate Professor Veterinary Clinical Sciences College of Veterinary Medicine Kansas State University Manhattan, Kansas Leptospirosis

Neil K. Harpster, VMD, DACVIM (Cardiology) Department of Cardiology Angell Memorial Animal Hospital Boston, Massachusetts Feline Cardiac Arrhythmias

Katrin Hartmann, Dr Med Vet, Dr Habil, DECVIM-CA Professor of Internal Medicine Head of Small Animal Internal Medicine Clinic University of Munich Munich, Germany Feline Leukemia Virus and Feline Immunodeficiency Virus

Elizabeth A. Hausner, DVM, DABT, DABVT Division of Cardio-Renal Drug Products Center for Drug Evaluation and Research U.S. Food and Drug Administration Beltsville, Maryland Herbal Hazards

Eleanor C. Hawkins, DVM, DACVIM Professor, Internal Medicine Department of Clinical Sciences College of Veterinary Medicine North Carolina State University Raleigh, North Carolina Pleural Effusion

xv

Diane V.H. Hendrix, DVM, DACVO

Rosemary A. Henik, DVM, MS, DACVIM (Internal Medicine) Clinical Associate Professor Department of Medical Sciences School of Veterinary Medicine University of Wisconsin Madison, Wisconsin Pulmonary Hypertension Systemic Hypertension

Carolyn J. Henry, DVM, MS, DACVIM (Oncology) Associate Professor of Oncology Department of Veterinary Medicine and Surgery College of Veterinary Medicine Department of Internal Medicine Division of Hematology/Oncology School of Medicine University of Missouri Columbia, Missouri Mammary Cancer

Michael E. Herrtage, MA, BVSc, DVSc, DVR, DVD, DSAM, MRCVS, DECVIM, DECVDI Reader in Small Animal Medicine Department of Veterinary Medicine University of Cambridge Cambridge, England United Kingdom Medical Management of Tracheal Collapse

A. Elizabeth Hershey, DVM, DACVIM (Oncology) Integrative Veterinary Oncology Phoenix, Arizona Feline Vaccine-Associated Sarcomas

Daniel G. Hicks, DVM Resident, Neurology and Neurosurgery Department of Veterinary Clinical Sciences Washington State University Pullman, Washington Treatment of Degenerative Lumbosacral Stenosis

xvi

Contributors

Mark E. Hitt, DVM, MS, DACVIM (Internal Medicine) Chief of Medicine Atlantic Veterinary Internal Medicine, LLC Annapolis, Maryland Drug-Associated Liver Disease

Gaby Hoffmann, DVM, Dr Med Vet, DACVIM Junior Lecturer, Clinical Genetics Clinical Sciences of Companion Animals Faculty of Veterinary Medicine Utrecht University Utrecht, The Netherlands Copper-Associated Chronic Hepatitis

Daniel F. Hogan, DVM, DACVIM (Cardiology) Associate Professor Chief of Comparative Cardiovascular Medicine Purdue University West Lafayette, Indiana Dilated Cardiomyopathy in Dogs

Kathleen M. Holan, DVM, DACVIM (Internal Medicine) Assistant Professor Department of Small Animal Clinical Sciences College of Veterinary Medicine Michigan State University East Lansing, Michigan Feline Hepatic Lipidosis

Steven R. Hollingsworth, DVM, DACVO Assistant Professor of Clinical Ophthalmology Department of Surgical and Radiological Sciences School of Veterinary Medicine University of California Davis, California Diseases of the Eyelids and Periocular Skin Ocular Immunotherapy

Bradford J. Holmberg, DVM, MS, PhD, DACVO Staff Ophthalmologist Veterinary Referral Centre Little Falls, New Jersey Ocular Neoplasia

David E. Holt, BVSc, DACVS Professor of Surgery School of Veterinary Medicine University of Pennsylvania Philadelphia, Pennsylvania Drainage Techniques for the Septic Abdomen

Heidi A. Hottinger, DVM, DACVS Department of Surgery Gulf Coast Veterinary Specialists Gulf Coast Veterinary Surgery Houston, Texas Canine Biliary Mucocele

Lynn R. Hovda, RPh, DVM, MS, DACVIM Director, Veterinary Services Safety Call International Bloomington, Minnesota Toxin Exposures in Small Animals

Lisa M. Howe, DVM, PhD, DACVS Associate Professor Department of Small Animal Medicine and Surgery College of Veterinary Medicine Texas A&M University College Station, Texas Early-Age Neutering in the Dog and Cat

Geraldine B. Hunt, BVSc, MvetClinStud, PhD, FACVSc Associate Professor University Veterinary Centre University of Sydney Sydney, New South Wales Australia Nasopharyngeal Disorders

Takuo Ishida, DVM Medical Director Akasaka Animal Hospital Tokyo, Japan Feline Infectious Peritonitis: Therapy and Prevention

Toshiroh Iwasaki, DVM, PhD, DACVIM Professor Department of Veterinary Internal Medicine Tokyo University of Agriculture & Technology Tokyo, Japan Interferons

Hilary A. Jackson, DVD, DACVD Dermatology Referral Services Glasgow, Scotland United Kingdom Hypoallergenic Diets: Principles in Therapy

Beth M. Johnson, DVM Resident, Internal Medicine Department of Small Animal Clinical Sciences College of Veterinary Medicine University of Tennessee Knoxville, Tennessee Canine Megaesophagus

Lynelle R. Johnson, DVM, PhD, DACVIM (SAIM) Assistant Professor Department of Medicine and Epidemiology School of Veterinary Medicine University of California Davis, California Chronic Bronchitis in Dogs Rhinitis in the Cat



Boyd R. Jones, BVSc, FACVSc, DECVIM, MRCVS Faculty of Veterinary Medicine University College Dublin Belfield, Dublin Ireland Hypokalemic Myopathy in Cats

Bruce W. Keene, DVM, MSc, DACVIM (Cardiology) Professor Department of Clinical Sciences College of Veterinary Medicine North Carolina State University Raleigh, North Carolina Management of Heart Failure in Dogs

Robert J. Kemppainen, DVM

Contributors

xvii

Rebecca Kirby, DVM, DACVIM (Internal Medicine), DACVECC Animal Emergency Center Glendale, Wisconsin Colloid Fluid Therapy Disseminated Intravascular Coagulation: Diagnosis and Management

Claudia A. Kirk, DVM, PhD, DACVN, DACVIM Associate Professor of Medicine and Nutrition Department of Small Animal Clinical Sciences College of Veterinary Medicine The University of Tennessee Knoxville, Tennessee Interpreting and Managing Crystalluria Obesity

Professor Department of Anatomy, Physiology, and Pharmacology College of Veterinary Medicine Auburn University Auburn, Alabama Interpretation of Endocrine Diagnostic Test Results for Adrenal and Thyroid Disease

Deborah W. Knapp, DVM, MS, DACVIM (Oncology)

Michael S. Kent, MAS, DVM

Stephanie J. Kottler, DVM

Assistant Professor Surgical and Radiological Sciences College of Veterinary Medicine University of California Davis, California Ocular Neoplasia

Resident, Small Animal Internal Medicine Department of Veterinary Medicine and Surgery College of Veterinary Medicine University of Missouri Columbia, Missouri Canine Anaplasma Infection

Marie E. Kerl, DVM, DACVIM (SAIM), DACVECC

Marc S. Kraus, DVM, DACVIM (Cardiology, Internal Medicine)

Clinical Associate Professor Department of Veterinary Medicine and Surgery University of Missouri Small Animal Medicine Section Head Veterinary Medical Teaching Hospital Columbia, Missouri Treatment of Anemia in Renal Failure

Faculty Department of Clinical Sciences College of Veterinary Medicine Cornell University Ithaca, New York Pacing in the Critical Care Setting Syncope Ventricular Arrhythmias in Dogs

Safdar A. Khan, DVM, MS, PhD, DABVT Director of Toxicology Research ASPCA Animal Poison Control Center Urbana, Illinois Recently Recognized Animal Toxicants

Chand Khanna, DVM, PhD Director, Comparative Oncology Program Center for Cancer Research National Cancer Institute National Institutes of Health Bethesda, Maryland Clinical Trials in Veterinary Oncology

Peter P. Kintzer, DVM, DACVIM Staff Internist Department of Medicine Boston Road Animal Hospital Springfield, Massachusetts Hypoadrenocorticism

Dolores L. McCall Professor of Veterinary Medicine (Comparative Oncology) Department of Veterinary Clinical Sciences Purdue University West Lafayette, Indiana Urinary Bladder Cancer

John M. Kruger, DVM, PhD, DACVIM Associate Professor Department of Small Animal Clinical Sciences College of Veterinary Medicine Michigan State University East Lansing, Michigan Management of Feline Nonobstructive Idiopathic Cystitis

Ned F. Kuehn, DVM, MS, DACVIM (SAIM) Chief of Internal Medicine Michigan Veterinary Specialists Southfield, Michigan Rhinitis in the Dog

xviii

Contributors

Michelle Anne Kutzler, DVM, PhD, DACT Assistant Professor Department of Clinical Sciences College of Veterinary Medicine Oregon State University Corvallis, Oregon Canine Postpartum Disorders

Andrew E. Kyles, BVMS, PhD, DACVS Professor, Small Animal Surgery Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California Davis, California Management of Feline Ureteroliths

Mary Anna Labato, DVM, DACVIM Clinical Associate Professor Section Head, Small Animal Medicine Department of Clinical Sciences Foster Hospital for Small Animals Cummings School of Veterinary Medicine Tufts University North Grafton, Massachusetts Uncomplicated Urinary Tract Infection

Susan E. Lana, DVM, MS, DACVIM (Oncology) Associate Professor Oncology Section Head Animal Cancer Center Department of Clinical Sciences Colorado State University Fort Collins, Colorado Canine Lymphoma

Michael R. Lappin, DVM, PhD, DACVIM (Internal Medicine) Assistant Department Head for Research The Kenneth Smith Professor in Small Animal Clinical Veterinary Medicine Department of Clinical Sciences College of Veterinary Medicine and Biomedical Sciences Colorado State University Fort Collins, Colorado Toxoplasmosis

Alfred M. Legendre, DVM, MS, DACVIM Assistant Department Chair Department of Small Animal Clinical Sciences College of Veterinary Medicine The University of Tennessee Knoxville, Tennessee Systemic Fungal Infections

Michael S. Leib, DVM, MS, DACVIM (SAIM) C.R. Roberts Professor of Small Animal Medicine Department of Small Animal Clinical Sciences College of Veterinary Medicine Virginia Polytechnic Institute and State University Blacksburg, Virginia Gastric Helicobacter spp. and Chronic Vomiting in Dogs

Christine C. Lim, DVM Resident, Comparative Ophthalmology Veterinary Medical Teaching Hospital University of California Davis, California Qualitative Tear Film Disturbances of Dogs and Cats

Gabriele A. Landolt, Dr Med Vet, MS, PhD

Julius M. Liptak, BVSc, MvetClinStud, FACVSc, DECVS, DACVS

Assistant Professor Department of Clinical Sciences College of Veterinary Medicine and Biomedical Sciences Colorado State University Fort Collins, Colorado Canine Influenza

Assistant Professor in Small Animal Surgery Department of Clinical Studies Ontario Veterinary College University of Guelph Guelph, Ontario Canada Canine Soft-Tissue Sarcomas

India F. Lane, DVM, MS, DACVIM

Remo Lobetti, BVSc (Hons), MMedVet (Med), PhD, DECVIM (Internal Medicine)

Associate Professor and Director of Educational Enhancement Department of Small Animal Clinical Sciences College of Veterinary Medicine The University of Tennessee Knoxville, Tennessee Urinary Incontinence and Micturition Disorders: Pharmacologic Management

Catherine E. Langston, DVM, DACVIM (SAIM) Section Head, Nephrology, Endocrinology, Urology, and Hemodialysis Animal Medical Center New York, New York Hemodialysis Treatment of Anemia in Renal Failure

Bryanston Veterinary Hospital Bryanston, South Africa Pneumocystosis

Dawn Logas, DVM, DACVD Staff Dermatologist Veterinary Dermatology Center Maitland, Florida Ear-Flushing Techniques

Cheryl A. London, DVM, PhD, DACVIM (Oncology) Associate Professor College of Veterinary Medicine The Ohio State University Columbus, Ohio Mast Cell Tumor



Contributors

Andrea L. Looney, DVM, DACVA

David J. Maggs, BVSc, DACVO

Senior Lecturer, Department of Clinical Sciences Section of Anesthesiology and Pain Management Cornell University Ithaca, New York Acute Pain Management

Associate Professor Department of Surgical and Radiological Sciences School of Veterinary Medicine University of California Davis, California Antiviral Therapy for Feline Herpesvirus Corneal Colors as a Diagnostic Aid Pearls of the Ophthalmic Examination

Jody P. Lulich, DVM, PhD, DACVIM (SAIM) Professor, Small Animal Medicine Department of Small Animal Clinical Sciences University of Minnesota St. Paul, Minnesota Laser Lithotripsy for Uroliths Incomplete Urolith Removal: Prevention, Detection, and Correction

Katharine F. Lunn, BVMS, MS, PhD, MRCVS, DACVIM (Internal Medicine), MRCVS Assistant Professor Department of Clinical Sciences College of Veterinary Medicine and Biomedical Sciences Colorado State University Fort Collins, Colorado Canine Influenza Managing the Patient With Polyuria and Polydipsia

Angela L. Lusby, DVM Resident in Clinical Nutrition and Graduate Research Assistant Department of Small Animal Clinical Sciences College of Veterinary Medicine The University of Tennessee Knoxville, Tennessee Obesity

John M. MacDonald, DVM, DACVD Associate Professor Department of Small Animal Surgery and Medicine College of Veterinary Medicine Auburn University Auburn, Alabama Acral Lick Dermatitis Allergen-Specific Immunotherapy

Kristin A. MacDonald, DVM, PhD, DACVIM (Cardiology) Staff Veterinary Cardiologist Medicine and Epidemiology University of California Davis, California Infective Endocarditis

Catriona M. MacPhail, DVM, PhD, DACVS Assistant Professor, Small Animal Surgery Department of Clinical Sciences College of Veterinary Medicine and Biomedical Sciences Colorado State University Fort Collins, Colorado Laryngeal Diseases

xix

Giovanni Majolino, DVM Majolino and Ranieri Veterinary Clinic Collecchio, Italy Aspermia/Oligozoospermia Caused by Retrograde Ejaculation in the Dog

Annie Malouin, DVM, DACVECC Metropolitan Veterinary Associates Norristown, Pennsylvania Shock

F. Anthony Mann, DVM, MS, DACVS, DACVECC Professor Department of Veterinary Medicine and Surgery College of Veterinary Medicine Director of Small Animal Emergency and Critical Care Services Small Animal Soft Tissue Surgery Service Chief Veterinary Medical Teaching Hospital University of Missouri Columbia, Missouri Acute Abdomen: Evaluation and Emergency Treatment

Denis J. Marcellin-Little, DEDV, DACVS, DECVS Associate Professor, Orthopedic Surgery College of Veterinary Medicine North Carolina State University Raleigh, North Carolina Medical Treatment of Coxofemoral Joint Disease

Rosanna Marsella, DVM, DACVD Associate Professor in Veterinary Dermatology Department of Small Animal Clinical Sciences College of Veterinary Medicine University of Florida Gainesville, Florida Pentoxifylline

Julie Martin, DVM, MS, DACVIM (Cardiology) Cardiologist Veterinary Heart and Lung Specialists Englewood, Colorado Cardioversion

Jocelyn A. Mason, DVM Consulting Veterinarian in Clinical Toxicology ASPCA Animal Poison Control Center Québec, Canada Recently Recognized Animal Toxicants

xx

Contributors

Karol A. Mathews, DVM, DVSc, DACVECC

Ellen Miller, DVM, MS, DACVIM

Professor Department of Clinical Studies Ontario Veterinary College University of Guelph Guelph, Ontario Canada Gastric Dilation-Volvulus

Peak Veterinary Internists PC Longmont, Colorado Immune-Mediated Hemolytic Anemia

Robert J. McCarthy, DVM, MS, DACVS Staff Veterinarian Department of Clinical Sciences Foster Hospital for Small Animals Cummings School of Veterinary Medicine Tufts University North Grafton, Massachusetts Emergency Management of Open Fractures

Susan A. McLaughlin, DVM, MS, DACVO Clinical Associate Professor Veterinary Administration School of Veterinary Medicine Purdue University West Lafayette, Indiana Differential Diagnosis of Blindness

Mary A. McLoughlin, DVM, MS, DACVS Associate Professor, Small Animal Surgery Department of Veterinary Clinical Sciences College of Veterinary Medicine The Ohio State University Columbus, Ohio Urinary Incontinence: Treatment With Injectable Bulking Agents

Matthew W. Miller, DVM, MS, DACVIM (Cardiology) Professor Department of Small Animal Clinical Sciences College of Veterinary Medicine and Biomedical Sciences Texas A&M University College Station, Texas Canine Heartworm Disease Patent Ductus Arteriosus

Paul E. Miller, DVM, DACVO Clinical Professor of Comparative Ophthalmology Department of Surgical Sciences School of Veterinary Medicine University of Wisconsin Madison, Wisconsin Feline Glaucoma

Darryl L. Millis, DVM, MS, DACVS Professor of Orthopedic Surgery Small Animal Clinical Sciences College of Veterinary Medicine University of Tennessee Knoxville, Tennessee Physical Therapy and Rehabilitation of Neurologic Patients

N. Sydney Moïse, DVM, MS, DACVIM (Cardiology, Internal Medicine)

Medical Director Florida Veterinary Specialists and Cancer Treatment Center Tampa, Florida Canine Megaesophagus

Professor Department of Clinical Sciences Chief of Cardiology Section College of Veterinary Medicine Cornell University Ithaca, New York Ventricular Arrhythmias in Dogs

Colleen Mendelsohn, DVM, DACVD

Cliff Monahan, DVM, PhD

Animal Dermatology Clinic Tustin, California Topical Therapy of Otitis Externa

Parasitologist Department of Veterinary Preventive Medicine College of Veterinary Medicine The Ohio State University Columbus, Ohio Appendix II: Treatment of Parasites

Erick A. Mears, DVM, DACVIM

Kathryn M. Meurs, DVM, PhD, DACVIM (Cardiology) Professor Department of Veterinary Clinical Sciences Washington State University Pullman, Washington Cardiomyopathy in Boxer Dogs Cardiomyopathy in Doberman Pinschers

Vicki N. Meyers-Wallen, VMD, PhD, DACT Associate Professor Baker Institute for Animal Health College of Veterinary Medicine Cornell University Ithaca, New York Inherited Disorders of the Reproductive Tract in Dogs and Cats

Eric Monnet, DVM, PhD, DACVS, DECVS Associate Professor, Small Animal Surgery Department of Clinical Sciences College of Veterinary Medicine and Biomedical Sciences Colorado State University Fort Collins, Colorado Laryngeal Diseases



Contributors

William E. Monroe, DVM, MS, DACVIM (SAIM)

Rusty Muse, DVM, DACVD

Professor, Small Animal Internal Medicine Department of Small Animal Clinical Sciences Virginia-Maryland Regional College of Veterinary Medicine Virginia Polytechnic Institute and State University Blacksburg, Virginia Canine Diabetes Mellitus

Animal Dermatology Clinic Tustin, California Diseases of the Anal Sac

Antony S. Moore, BVSc, MVSc, DACVIM (Oncology) Veterinary Oncology Consultants Wauchope, New South Wales Australia Anticancer Drugs and Protocols: Traditional Drugs

Lisa E. Moore, DVM, DACVIM (SAIM) Staff Internist Affiliated Veterinary Specialists Maitland, Florida Protein-Losing Enteropathy

Peter F. Moore, BVSc, PhD Professor Department of Pathology, Microbiology, and Immunology College of Veterinary Medicine University of California Davis, California Histiocytic Disease Complex

Adam Mordecai, DVM, DACVIM Veterinary Medical Referral Service Veterinary Specialty Center Buffalo Grove, Illinois Rational Use of Glucocorticoids in Infectious Disease

Karen A. Moriello, DVM, DACVD Professor Clinical Professor of Dermatology Department of Medical Sciences School of Veterinary Medicine University of Wisconsin Madison, Wisconsin Treatment of Dermatophytosis

Daniel O. Morris, DVM, DACVD

Masahiko Nagata, DVM, PhD, DAICVD (Asian College of Veterinary Dermatology) Animal Dermatology Center Tokyo, Japan Canine Papillomaviruses

Larry A. Nagode, DVM, PhD Department of Veterinary Biosciences Goss Laboratory The Ohio State University Columbus, Ohio Treatment of Hypoparathyroidism

Jill Narak, DVM Neurology/Neurosurgery Resident Department of Clinical Sciences College of Veterinary Medicine Auburn University Auburn, Alabama Treatment of Intracranial Tumors

Jennifer A. Neel, DVM, DACVP (Clinical Pathology) Assistant Professor College of Veterinary Medicine North Carolina State University Raleigh, North Carolina Thrombocytopenia

Reto Neiger, Dr Med Vet, PhD, DACVIM, DECVIM (CA) Professor in Small Animal Medicine Veterinärmedizinische Fakultät, Klinik für Kleintiere (Innere Medizin & Chirurgie) Giessen, Germany Canine Hyperadrenocorticism Gastric Ulceration

O. Lynne Nelson, DVM, MS, DACVIM (Internal Medicine, Cardiology)

Associate Professor of Dermatology College of Veterinary Medicine University of Pennsylvania Philadelphia, Pennsylvania Feline Demodicosis Therapy of Malassezia Infections and Malassezia Hypersensitivity

Associate Professor Veterinary Clinical Sciences College of Veterinary Medicine Washington State University Pullman, Washington Pericardial Effusion

Michael J. Murphy, DVM, PhD, DACT

Professor, Internal Medicine Department of Medicine and Epidemiology School of Veterinary Medicine University of California Davis, California Canine Hypercalcemia and Primary Hyperparathyroidism

Professor in Veterinary Population Medicine Veterinary Diagnostic Labs University of Minnesota St. Paul, Minnesota Food Toxicoses in Small Animals Nephrotoxicants Rodenticide Toxicoses Small Animal Poisoning: Additional Considerations Related to Legal Claims Sources of Help for Toxicosis

xxi

Richard W. Nelson, DVM, DACVIM

xxii

Contributors

Belle M. Nibblett, DVM

Philip Padrid, RN, DVM, DACVIM

Resident, Small Animal Medicine Department of Small Animal Clinical Sciences Western College of Veterinary Medicine University of Saskatchewan Saskatoon, Saskatchewan Canada von Willebrand’s Disease and Other Hereditary Coagulopathies

Adjunct Associate Professor Small Animal Medicine College of Veterinary Medicine The Ohio State University Columbus, Ohio; Committee on Molecular Medicine Pritzker School of Medicine The University of Chicago Chicago, Illinois Chronic Bronchitis and Asthma in Cats

Roberto E. Novo, DVM, DACVS University of Minnesota College of Veterinary Medicine St. Paul, Minnesota Surgical Repair of Vaginal Anomalies in the Bitch

Frederick W. Oehme, DVM, MS, PhD, DABVT, DABT, DATS Professor of Toxicology, Pathobiology, Medicine, and Physiology Department of Diagnostic Medicine/Pathobiology Comparative Toxicology Laboratories Kansas State University Manhattan, Kansas Urban Legends of Toxicology: Facts and Fiction

Carl A. Osborne, DVM, PhD, DACVIM Veterinary Clinical Sciences Department College of Veterinary Medicine University of Minnesota St. Paul, Minnesota Calcitriol Evidence-Based Management of Chronic Kidney Disease Incomplete Urolith Removal: Prevention, Detection, and Correction Management of Feline Nonobstructive Idiopathic Cystitis

Elizabeth O’Toole, BSc, DVM, DVSc, DACVECC Advanced Care Unit Mississauga/Oakville Veterinary Emergency Hospital and Referral Group Oakville, Ontario Canada Ventilator Therapy

Catherine A. Outerbridge, DVM, MVSC, DACVIM Dermatology Service Veterinary Medical Teaching Hospital University of California Davis, California Diseases of the Eyelids and Periocular Skin Nonneoplastic Nodular Histiocytic Diseases of the Skin

Mark A. Oyama, DVM, DACVIM Department of Clinical Studies School of Veterinary Medicine University of Pennsylvania Philadelphia, Pennsylvania Permanent Cardiac Pacing in Dogs

David L. Panciera, DVM, MS, DACVIM (SAIM) Professor Department of Small Animal Clinical Sciences Virginia-Maryland Regional College of Veterinary Medicine Virginia Polytechnic Institute and State University Blacksburg, Virginia von Willebrand’s Disease and Other Hereditary Coagulopathies

Melissa Paoloni, DVM, DACVIM (Oncology) Comparative Oncology Program National Cancer Institute National Institutes of Health Bethesda, Maryland Clinical Trials in Veterinary Oncology

Mark G. Papich, DVM, MS, DACVCP Professor of Clinical Pharmacology College of Veterinary Medicine North Carolina State University Raleigh, North Carolina Appendix I: Table of Common Drugs: Approximate Dosages

Nolie K. Parnell, DVM, DACVIM Clinical Assistant Professor Small Animal Internal Medicine Veterinary Clinical Sciences Purdue University West Lafayette, Indiana Chronic Colitis

Edward E. (Ned) Patterson, DVM, PhD, DACVIM Assistant Professor, Medicine, Genetics, and Epilepsy Department of Veterinary Clinical Sciences College of Veterinary Medicine University of Minnesota St. Paul, Minnesota Methods and Availability of Tests for Hereditary Disorders of Dogs

Mark E. Peterson, DVM, DACVIM Head of Endocrinology Department of Medicine, Bobst Hospital Associate Director, Caspary Research Institute Chairman, Institute of Postgraduate Education The Animal Medical Center New York, New York Hypoadrenocorticism Radioiodine for Feline Hyperthyroidism



Simon R. Platt, BVM&S, MRCVS, DECVN, DACVIM (Neurology) RCVS and European Specialist in Veterinary Neurology Neurology/Neurosurgery Service Head Animal Health Trust Centre for Small Animal Studies Suffolk, England United Kingdom Treatment of Cerebrovascular Disease

Michael Podell, MSc, DVM, DACVIM (Neurology) Neurology and Neurosurgery Service Animal Emergency and Referral Center Northbrook, Illinois Adjunct Professor Department of Clinical Sciences College of Veterinary Medicine University of Illinois at Urbana-Champaign Urbana, Illinois Treatment of Status Epilepticus

David J. Polzin, DVM, PhD, DACVIM (Internal Medicine) Professor Department of Veterinary Clinical Sciences College of Veterinary Medicine University of Minnesota St. Paul, Minnesota Calcitriol Evidence-Based Management of Chronic Kidney Disease

Eric R. Pope, DVM, MS, DACVS Professor, Small Animal Surgery Ross University School of Veterinary Medicine Basseterre, St. Kitts West Indies Brachycephalic Upper Airway Syndrome in Dogs

Robert H. Poppenga, DVM, PhD, DABT CAHFS Toxicology Laboratory School of Veterinary Medicine University of California Davis, California Herbal Hazards

Lynn O. Post, DVM, PhD, DABVT Director, Division of Surveillance Office of Surveillance and Compliance Rockville, Maryland Reporting an Adverse Drug Reaction to the Food and Drug Administration

Cynthia C. Powell, DVM, MS, DACVO Associate Professor, Veterinary Ophthalmology Department of Clinical Sciences College of Veterinary Medicine and Biomedical Sciences Colorado State University Fort Collins, Colorado Anterior Uveitis in Dogs and Cats

Contributors

xxiii

Barrak M. Pressler, DVM, DACVIM (SAIM) Assistant Professor of Internal Medicine Department of Veterinary Clinical Sciences Purdue University West Lafayette, Indiana Cancer and the Kidney

Jennifer E. Prittie, DVM, DACVIM (Internal Medicine), DACVECC Criticalist Department of Emergency Medicine and Critical Care The Animal Medical Center New York, New York Adrenal Insufficiency in Critical Illness

Beverly J. Purswell, DVM, PhD, DACT Professor of Theriogenology Virginia-Maryland Regional College of Veterinary Medicine Virginia Polytechnic Institute and State University Blacksburg, Virginia Use of Vaginal Cytology and Vaginal Cultures for Breeding Management and Diagnosis of Reproductive Tract Disease

R. Lee Pyle, VMD, MS, DACVIM (Cardiology) Professor Emeritus Department of Small Animal Clinical Sciences Virginia-Maryland College of Veterinary Medicine Virginia Polytechnic Institute and State University Blacksburg, Virginia Subaortic Stenosis

Ian Ramsey, BVSc, PhD, DSAM Dip, ECVIM-CA, MRCVS Senior Lecturer in Small Animal Medicine Faculty of Veterinary Medicine University of Glasgow Glasgow, Scotland United Kingdom Canine Hyperadrenocorticism

Jacquie S. Rand, BVSc(Hons), DVSc, DACVIM (SAIM) Professor of Companion Animal Health Director, Centre for Companion Animal Health School of Veterinary Science Faculty of Natural Resources, Agriculture, and Veterinary Science The University of Queensland Brisbane, Queensland Australia Feline Diabetes Mellitus

Claudia E. Reusch, DVM, DECVIM-CA Professor Clinic of Small Animal Internal Medicine Vetsuisse Faculty University of Zurich Zurich, Switzerland Diabetic Monitoring

xxiv

Contributors

Keith P. Richter, DVM, DACVIM (SAIM)

Edmund J. Rosser, Jr., DVM, DACVD

Hospital Director and Internal Medicine Staff Department of Internal Medicine Veterinary Specialty Hospital of San Diego San Diego, California Feline Gastrointestinal Lymphoma

Professor and Head of Dermatology Department of Small Animal Clinical Sciences College of Veterinary Medicine Michigan State University East Lansing, Michigan Sebaceous Adenitis

Kenita S. Rogers, DVM, MS, DACVIM (Internal Medicine, Oncology) Professor and Associate Department Head Small Animal Clinical Sciences College of Veterinary and Biomedical Sciences Texas A&M University College Station, Texas Collection of Specimens for Cytology

Stefano Romagnoli, DVM, MS, PhD, DECAR (European College of Animal Reproduction)

Jan Rothuizen, DVM, PhD, DECVIM-CA Professor of Internal Medicine Chair, Department of Clinical Sciences of Companion Animals Faculty of Veterinary Medicine University of Utrecht Utrecht, The Netherlands Copper-Associated Chronic Hepatitis

Philip Roudebush, DVM, DACVIM (SAIM)

Professor, Clinical Veterinary Reproduction University of Padova Legnaro, Italy Aspermia/Oligozoospermia Caused by Retrograde Ejaculation in the Dog

Director, Scientific Affairs Hill’s Pet Nutrition, Inc. Topeka, Kansas Flatulence

Margaret V. Root Kustritz, DVM, PhD, DACT

Director of Education Animal Emergency Center Glendale, Wisconsin Colloid Fluid Therapy Disseminated Intravascular Coagulation: Diagnosis and Management

Assistant Clinical Specialist, Small Animal Reproduction College of Veterinary Medicine University of Minnesota St. Paul, Minnesota Intermittent Erection of the Penis in Castrated Male Dogs Ovarian Remnant Syndrome in Cats Toxicology of Veterinary and Human Estrogen and Progesterone Formulations in Dogs Vaginitis

Wayne S. Rosenkrantz, DVM, DACVD Partner Animal Dermatology Clinics Tustin, Marina del Rey, and San Diego, California House Dust Mites and Their Control Pyotraumatic Dermatitis (“Hot Spots”) Shampoo Therapy

Linda Ross, DVM, MS, DACVIM (SAIM) Associate Professor Department of Clinical Sciences Cummings School of Veterinary Medicine Tufts University North Grafton, Massachusetts Acute Renal Failure

Sheri Ross, BSc, DVM, PhD, DACVIM (Internal Medicine) Hemodialysis/Nephrology Service University of California Medical Center San Diego, California Calcitriol Evidence-Based Management of Chronic Kidney Disease

Elke Rudloff, DVM, DACVECC

Wilson K. Rumbeiha, DVM, PhD, DABVT, DABT Associate Professor, Pathobiology and Diagnostic Investigation Section Chief, Toxicology Diagnostic Center for Population and Animal Health College of Veterinary Medicine Michigan State University Lansing, Michigan Nephrotoxicants Parasiticide Toxicoses: Avermectins

Clare Rusbridge, BVMS, PhD, MRCVS, DECVN Stone Lion Veterinary Centre Wimbledon Village London, England United Kingdom Treatment of Canine Chiari-Like Malformation and Syringomyelia

John E. Rush, DVM, MS, DACVIM (Cardiology), DACVECC Professor and Associate Department Chair Department of Clinical Sciences Cummings School of Veterinary Medicine Tufts University North Grafton, Massachusetts Chronic Valvular Disease in Dogs



Contributors

xxv

Marco Russo, DVM, PhD

Howard B. Seim, III, DVM, DACVS

Lecturer Veterinary Clinical Sciences Veterinary School of Naples “Federico II” University of Naples Naples, Italy Breeding Management of the Bitch

Professor Department of Clinical Sciences College of Veterinary Medicine and Biomedical Sciences Colorado State University Fort Collins, Colorado Esophageal Feeding Tubes

Sherry Lynn Sanderson, DVM, PhD, DACVIM, DACVN

Rance K. Sellon, DVM, PhD, DACVIM

Associate Professor Department of Physiology and Pharmacology College of Veterinary Medicine University of Georgia Athens, Georgia Measuring Glomerular Filtration Rate: Practical Use of Clearance Tests

H. Mark Saunders, VMD, MS, DACVR Partner Lynks Group PLC—Veterinary Imaging Shelburne, Vermont Noncardiogenic Pulmonary Edema

Patricia A. Schenck, DVM, PhD Endocrine Diagnostic Section Chief Assistant Professor Department of Pathobiology and Diagnostic Investigation Diagnostic Center for Population and Animal Health Michigan State University Lansing, Michigan Idiopathic Feline Hypercalcemia Treatment of Hypoparathyroidism

Karsten E. Schober, DVM, PhD, DECVIM (Cardiology) Assistant Professor Department of Veterinary Clinical Sciences College of Veterinary Medicine The Ohio State University Columbus, Ohio Myocarditis

Gretchen L. Schoeffler, DVM, DACVECC Chief, Section of Veterinary Emergency and Critical Care Cornell University Hospital for Animals Cornell University Ithaca, New York Cardiopulmonary Cerebral Resuscitation

J. Catharine R. Scott-Moncrieff, MA, Vet MB, MS, MRCVS, DACVIM (SAIM), DECVIM (Companion Animal) Professor Department of Veterinary Clinical Sciences School of Veterinary Medicine Purdue University West Lafayette, Indiana Atypical and Subclinical Hyperadrenocorticism Hypothyroidism

Associate Professor Department of Small Animal Medicine College of Veterinary Medicine Washington State University Pullman, Washington Rational Use of Glucocorticoids in Infectious Disease Systemic Fungal Infections

Scott P. Shaw, DVM, DACVECC Assistant Professor Section of Emergency and Critical Care Department of Clinical Sciences Cummings School of Veterinary Medicine Tufts University North Grafton, Massachusetts Hospital-Acquired Bacterial Infections Thoracic Trauma

G. Diane Shelton, DVM, PhD, DACVIM (Internal Medicine) Professor, Department of Pathology Director, Comparative Neuromuscular Laboratory School of Medicine University of California San Diego and La Jolla, California Oropharyngeal Dysphagia Treatment of Autoimmune Myasthenia Gravis Treatment of Myopathies and Neuropathies

Robert G. Sherding, DVM, DACVIM (Internal Medicine) Professor of Internal Medicine Department of Veterinary Clinical Sciences College of Veterinary Medicine The Ohio State University Columbus, Ohio Respiratory Parasites

Deborah Silverstein, DVM, DACVECC Assistant Professor, Critical Care Department of Clinical Studies School of Veterinary Medicine University of Pennsylvania Philadelphia, Pennsylvania Shock

Kenneth W. Simpson, BVM&S, PhD, DACVIM, DECVIM-CA Associate Professor of Medicine College of Veterinary Medicine Cornell University Ithaca, New York Canine Ulcerative Colitis

xxvi

Contributors

Kaitkanoke Sirinarumitr, DVM, MS, PhD Assistant Professor, Faculty of Veterinary Medicine Department of Obstetrics, Gynaecology, and Animal Reproduction Veterinary Teaching Hospital Kasetsart University Bangkok, Thailand Medical Treatment of Benign Prostatic Hypertrophy and Prostatitis in Dogs

D. David Sisson, DVM, DACVIM (Cardiology) Department of Clinical Sciences College of Veterinary Medicine Oregon State University Corvallis, Oregon Permanent Cardiac Pacing in Dogs

Daniel D. Smeak, DVM, DACVS Professor Department of Veterinary Clinical Sciences College of Veterinary Medicine The Ohio State University Columbus, Ohio Pneumothorax

Annette N. Smith, DVM, MS, DACVIM (Oncology, SAIM)

Jörg M. Steiner, Dr Med Vet, PhD, DACVIM, DECIVM-CA Associate Professor and Director of the GI Lab Small Animal Clinical Sciences Texas A&M University College Station, Texas Canine Pancreatic Disease

Rebecca L. Stepien, DVM, MS, DACVIM (Cardiology) Clinical Associate Professor, Cardiology Department of Medical Sciences Cardiology Service Head Veterinary Teaching Hospital School of Veterinary Medicine University of Wisconsin Madison, Wisconsin Systemic Hypertension

Jennifer E. Stokes, DVM, DACVIM (Internal Medicine) Clinical Assistant Professor Department of Small Animal Clinical Sciences University of Tennessee Knoxville, Tennessee Diagnostic Approach to Acute Azotemia

Associate Professor Department of Clinical Sciences College of Veterinary Medicine Auburn University Auburn, Alabama Treatment of Intracranial Tumors

Beverly K. Sturges, DVM, DACVIM (Neurology)

Frances O. Smith, DVM, PhD, DACT

Jane E. Sykes, BVSc(Hons), PhD, DACVIM (Internal Medicine)

President, Orthopedic Foundation for Animals Smith Veterinary Hospital Burnsville, Minnesota Pyometra

Patricia J. Smith, DVM, MS, PhD, DACVO Animal Eye Care Fremont, California Retinal Detachment

Candace A. Sousa, DVM, DABVP (Canine and Feline Practice), DACVD Senior Veterinary Specialist, Veterinary Specialty Team Pfizer Animal Health El Dorado Hills, California Glucocorticoids in Veterinary Dermatology

Alan W. Spier, DVM, PhD, DACVIM (Cardiology) Florida Veterinary Specialists Tampa, Florida Cardiomyopathy in Boxer Dogs

Wayne Spoo, DVM, DABVT, DABT Master Toxicologist Scientific and Regulatory Affairs RJ Reynolds Tobacco Co. Winston-Salem, North Carolina Nicotine Toxicosis

Assistant Clinical Professor, Neurology/Neurosurgery Department of Surgery and Radiology University of California Davis, California Diagnosis and Treatment of Atlantoaxial Subluxation

Assistant Professor of Small Animal Internal Medicine Department of Medicine and Epidemiology University of California Davis, California Feline Calicivirus Infection Feline Chlamydiosis

Patricia A. Talcott, DVM, MS, PhD, DABVT Associate Professor Department of Veterinary Comparative Anatomy, Pharmacology, and Physiology College of Veterinary Medicine Washington State University; Veterinary Diagnostic Toxicologist Washington Animal Disease Diagnostic Laboratory Pullman, Washington Insecticide Toxicosis

Séverine Tasker, BSc, BVSc, PhD, DSAM, DECVIM-CA, MRCVS Lecturer in Small Animal Medicine School of Clinical Veterinary Science University of Bristol Bristol, England United Kingdom Canine and Feline Hemotropic Mycoplasmosis



Contributors

xxvii

Marion B. Tefend, RVT

David C. Twedt, DVM, DACVIM (Internal Medicine)

Clinical Instructor ICU Nursing Supervisor Department of Clinical Sciences College of Veterinary Medicine Auburn University Auburn, Alabama Vascular Access Techniques

Professor Department of Clinical Sciences College of Veterinary Medicine and Biomedical Sciences Colorado State University Fort Collins, Colorado Evaluation of Elevated Serum Alkaline Phosphatase in the Dog Feline Inflammatory Liver Disease

Douglas H. Thamm, VMD, DACVIM (Oncology)

Shelly L. Vaden, DVM, PhD, DACVIM

Assistant Professor, Oncology Department of Clinical Sciences College of Veterinary Medicine and Biomedical Sciences Colorado State University Fort Collins, Colorado Anticancer Drugs: New Drugs

Andrea Tipold, Dr Med Vet, DECVN Professor of Neurology Department Small Animal Medicine and Surgery University of Veterinary Medicine Hannover, Germany Treatment of Primary Central Nervous System Inflammation (Encephalitis and Meningitis)

Anthony H. Tobias, DVM, DACVIM (Cardiology) Associate Professor Veterinary Clinical Sciences University of Minnesota St. Paul, Minnesota Arterial Thromboembolism in Cats

Karen M. Tobias, DVM, MS, DACVS Professor Department of Small Animal Clinical Sciences College of Veterinary Medicine University of Tennessee Knoxville, Tennessee Portosystemic Shunts

Lauren A. Trepanier, DVM, PhD, DACVIM, DACVCP Associate Professor Department of Medical Sciences School of Veterinary Medicine University of Wisconsin Madison, Wisconsin Medical Treatment of Feline Hyperthyroidism

Gregory C. Troy, DVM, MS, DACVIM (Internal Medicine) Professor and Department Head Dr. and Mrs. Dorsey Taylor Mahin Endowed Professor Department of Small Animal Clinical Sciences Virginia-Maryland Regional College of Veterinary Medicine Virginia Polytechnic Institute and State University Blacksburg, Virginia American Leishmaniasis

Professor, Internal Medicine Department of Clinical Sciences College of Veterinary Medicine North Carolina State University Raleigh, North Carolina Glomerular Disease

David M. Vail, DVM, DACVIM (Oncology) Professor of Oncology Director, Center for Clinical Trials and Research Department of Medical Sciences School of Veterinary Medicine University of Wisconsin Madison, Wisconsin Anticancer Drugs: New Drugs Paraneoplastic Hypercalcemia

Amy K. Valentine, DVM, MS Private Specialty Practitioner Oregon Veterinary Referral Associates Springfield, Oregon Pneumothorax

Carlo Vitale, DVM, DACVD Staff Dermatologist San Francisco Veterinary Specialists, Inc. San Francisco, California Methicillin-Resistant Canine Pyoderma

Petra A. Volmer, DVM, MS, DABVT, DABT Assistant Professor of Toxicology Departments of Veterinary Biosciences and Veterinary Diagnostic Laboratory College of Veterinary Medicine University of Illinois at Urbana-Champaign Urbana, Illinois Human Drugs of Abuse

Daniel A. Ward, DVM, PhD, DACVO Professor of Ophthalmology College of Veterinary Medicine University of Tennessee Knoxville, Tennessee Ocular Pharmacology

Wendy A. Ware, DVM, MS, DACVIM (Cardiology) Professor Departments of Veterinary Clinical Sciences and Biomedical Sciences Staff Cardiologist Veterinary Teaching Hospital Iowa State University Ames, Iowa Pericardial Effusion

xxviii

Contributors

A.D.J. Watson, BVSc, PhD, FRCVS, MACVSc, DECVPT

Michael D. Willard, DVM, MS, DACVIM (Internal Medicine)

Glebe, New South Wales Australia Chronic Kidney Disease: Staging and Management

Professor Department of Small Animal Medicine and Surgery College of Veterinary Medicine and Biomedical Sciences Texas A&M University College Station, Texas Esophagitis

Craig B. Webb, DVM, PhD, DACVIM (SAIM) Assistant Professor Department of Clinical Sciences College of Veterinary Medicine and Biomedical Sciences Colorado State University Fort Collins, Colorado Anal-Rectal Disease

Cynthia R.L. Webster, DVM, DACVIM (Internal Medicine) Associate Professor Department of Clinical Sciences Cummings School of Veterinary Medicine Tufts University North Grafton, Massachusetts Diagnostic Approach to Hepatobiliary Disease Ursodeoxycholic Acid Therapy

Douglas J. Weiss, DVM, DACVP Professor, Veterinary and Biomedical Sciences University of Minnesota St. Paul, Minnesota Nonregenerative Anemias

Chick W.C. Weisse, VMD, DACVS Assistant Professor of Surgery Director of Interventional Radiology Services Veterinary Hospital of the University of Pennsylvania Philadelphia, Pennsylvania Interventional Radiology in Urinary Diseases Intraluminal Stenting for Tracheal Collapse

Elias Westermarck, DVM, PhD, DECVIM Emeritus Professor of Medicine Department of Clinical Veterinary Sciences University of Helsinki, Helsinki, Finland Tylosin-Responsive Diarrhea

Jodi L. Westropp, DVM, PhD, DACVIM Assistant Professor Department of Medicine and Epidemiology College of Veterinary Medicine University of California Davis, California Management of Feline Ureteroliths Urinary Incontinence and Micturition Disorders: Pharmacologic Management

Maria Wiberg, DVM, PhD Member of the Gastrointestinal Research Group Department of Clinical Veterinary Sciences Faculty of Veterinary Medicine University of Helsinki Helsinki, Finland Exocrine Pancreatic Insufficiency in Dogs

David A. Williams, MA, VetMB, PhD, DACVIM, DECVIM-CA Professor and Head Department of Veterinary Clinical Medicine University of Illinois at Urbana-Champaign Urbana, Illinois Feline Exocrine Pancreatic Disease

Marion S. Wilson, BVMS, MVSc MRCVS Director, TCI Ltd Te Kuiti, New Zealand Endoscopic Transcervical Insemination

James S. Wohl, DVM, DACVIM, DACVECC Professor Department of Clinical Sciences College of Veterinary Medicine Auburn University Auburn, Alabama Vascular Access Techniques

J. Paul Woods, DVM, MS, DACVIM (Oncology, Internal Medicine), CVMA Associate Professor Department of Clinical Studies Ontario Veterinary Teaching Hospital University of Guelph Guelph, Ontario Canada Feline Cytauxzoonosis

Kathy N. Wright, DVM, DACVIM (Cardiology, Internal Medicine) Director of Cardiovascular Medicine Internal Medicine The CARE Center Cincinnati, Ohio Assessment and Treatment of Supraventricular Tachyarrhythmias

Debra L. Zoran, DVM, PhD, DACVIM (SAIM) Associate Professor of Internal Medicine Small Animal Clinical Sciences College of Veterinary Medicine and Biomedical Sciences Texas A&M University College Station, Texas Diet and Diabetes

Contributors to Evolve Chapters by the following contributors were published in CVT XIII and are now available on Evolve at http:// evolve.elsevier.com/Bonagura/Kirks/.

Verena K. Affolter, DVM, PhD Associate Professor for Clinical Dermatopathology Department of Pathology, Microbiology, and Immunology School of Veterinary Medicine University of California Davis, California Immunophenotyping in the Dog

F. J. Allan, BVSc, MVSc Lecturer Companion Animal Medicine Centre for Companion Animal Health Institute of Veterinary, Animal, and Biomedical Sciences Massey University Palmerston North, New Zealand Assessment of Gastrointestinal Motility

Philip J. Bergman, DVM, MS, PhD, DACVIM (Oncology) Chief Medical Officer Bright Heart Veterinary Centers Armonk, New York Multidrug Resistance

G. Daniel Boon, DVM, MS, DACVP President and Director of Pathology United Veterinary Laboratories Garden Grove, California Interpretation of Cytograms and Histograms of Erythrocytes, Leukocytes, and Platelets

Edward B. Breitschwerdt, DVM, DACVIM Professor of Medicine and Infectious Diseases Director, NCSU-CVM Biosafety Laboratory Adjunct Associate Professor of Medicine Duke University Medical Center Department of Clinical Sciences College of Veterinary Medicine North Carolina State University Raleigh, North Carolina Why Are Infectious Diseases Emerging?

Scott A. Brown, VMD, PhD, DACVIM Josiah Meigs Distinguished Teaching Professor and Department Head Small Animal Medicine and Surgery College of Veterinary Medicine University of Georgia Athens, Georgia The Kidney and Hyperthyroidism

Elaine R. Caplan, DVM, DABVP Surgery Instructor Veterinary Teaching Hospital Iowa State University Ames, Iowa Treatment of Insulinoma in the Dog, Cat, and Ferret

Sharon A. Center, DVM, DACVIM Professor, Internal Medicine College of Veterinary Medicine Cornell University Ithaca, New York Hepatoportal Microvascular Dysplasia

Mary M. Christopher, DVM, PhD, DACVP Department of Pathology, Microbiology, and Immunology School of Veterinary Medicine Clinician, Veterinary Teaching Hospital University of California Davis, California Disorders of Feline Red Blood Cells

Leah A. Cohn, DVM, PhD, DACVIM (SAIM) Associate Professor of Veterinary Internal Medicine Department of Veterinary Medicine and Surgery College of Veterinary Medicine University of Missouri Columbia, Missouri Diagnosis and Treatment of Parvovirus

Gheorge M. Constantinescu, DVM, PhD, Drhc Professor of Veterinary Anatomy College of Veterinary Medicine University of Missouri Columbia, Missouri Feline Respiratory Tract Polyps

Laine A. Cowan, DVM, DACVIM Associate Professor Department of Clinical Sciences College of Veterinary Medicine Kansas State University Manhattan, Kansas Cutaneous and Renal Glomerulopathy of Greyhound Dogs xxix

xxx

Contributors to Evolve

Dennis T. Crowe, Jr., DVM, NREMT-I, PI, CFF, DACVS, DACVECC President Veterinary Surgery, Emergency and Critical Care Services and Consulting Bogart, Georgia Microenteral Nutrition

Deborah J. Davenport, DVM, MS, DACVIM Hill’s Pet Nutrition, Inc. Topeka, Kansas Small Intestinal Bacterial Overgrowth

Helio Autran de Morais, DVM, PhD, DACVIM (SAIM, Cardiology) Clinical Associate Professor Department of Medical Sciences University of Wisconsin Madison, Wisconsin Feline Congenital Heart Disease

Jennifer J. Devey, DVM, DACVECC Head of Emergency and Critical Care Services California Animal Hospital Los Angeles, California Microenteral Nutrition

Nishi Dhupa, BVM, DACVIM (Internal Medicine), DACVECC Director of Emergency and Critical Care Department of Clinical Sciences College of Veterinary Medicine Cornell University Ithaca, New York Sodium Nitroprusside: Uses and Precautions

Stephen P. DiBartola, DVM, DACVIM (SAIM) Professor Department of Veterinary Clinical Sciences College of Veterinary Medicine The Ohio State University Columbus, Ohio The Kidney and Hyperthyroidism

Steven W. Dow, DVM, PhD Professor Department of Microbiology, Immunology, and Pathology College of Veterinary Medicine and Biomedical Sciences Colorado State University Fort Collins, Colorado Why Are Infectious Diseases Emerging?

Cherie L. Drenzek, DVM, MS Chief, Notifiable Diseases Epidemiology Section Georgia Division of Public Health Atlanta, Georgia The Rabies Pandemic

Lisa A. Dzyban, DVM, DACVIM Phoenix Central Laboratory Everett, Washington Peritoneal Dialysis

Sidney A. Ewing, DVM, PhD Wendell H. & Nellie G. Krull Professor Emeritus of Veterinary Parasitology Oklahoma State University Stillwater, Oklahoma Ticks as Vectors of Companion Animal Diseases

Leah S. Faudskar, DVM, DACVECC Prairie Pet Clinic Fosston Valley, Minnesota Point-of-Care Laboratory Testing in the Intensive Care Unit

Edward C. Feldman, DVM, DACVIM Professor Department of Medicine and Epidemiology School of Veterinary Medicine University of California Davis, California Diagnosis and Management of Large Pituitary Tumors in Dogs With Pituitary-Dependent Hyperadrenocorticism

Peter J. Felsburg, VMD, PhD Trustee Professor of Immunology Department of Clinical Studies Veterinary School of Medicine University of Pennsylvania Philadelphia, Pennsylvania Hereditary and Acquired Immunodeficiency Diseases

Urs Giger, PD, Dr Med Vet, MS, FVH, DACVIM, DECVIM, DECVCP Charlotte Newton Sheppard Professor of Medicine Chief of Medical Genetics Department of Clinical Studies School of Veterinary Medicine University of Pennsylvania Philadelphia, Pennsylvania Hereditary Erythrocyte Disorders

Brian C. Gilger, DVM, MS, DACVO Professor of Ophthalmology Department of Clinical Sciences North Carolina State University Raleigh, North Carolina Diagnosis and Treatment of Canine Conjunctivitis Ocular Manifestations of Systemic Diseases

Elizabeth A. Giuliano, DVM, MS, DACVO Assistant Professor Department of Veterinary Medicine and Surgery University of Missouri Columbia, Missouri Keratoconjunctivitis Sicca

Tony Glover, DVM, MS, DACVO College of Veterinary Medicine The Ohio State University Columbus, Ohio Ocular Emergencies



Jody L. Gookin, DVM, PhD, DACVIM (Internal Medicine) Assistant Professor, Molecular Biomedical Sciences College of Veterinary Medicine North Carolina State University Raleigh, North Carolina Indications for Nephrectomy and Nephrotomy

Marielle Goossens, DVM, DACVIM East Bay Veterinary Specialists Walnut Creek, California Diagnosis and Management of Large Pituitary Tumors in Dogs With Pituitary-Dependent Hyperadrenocorticism

Deborah S. Greco, DVM, PhD, DACVIM Nestle Purina Petcare St. Louis, Missouri Treatment of Non–Insulin-Dependent Diabetes Mellitus in Cats Using Oral Hypoglycemic Agents

W. Grant Guilford, BVSc, BPhil, PhD, FACVSc, DACVIM Institute of Veterinary, Animal, and Biomedical Sciences Massey University Palmerston North, New Zealand Assessment of Gastrointestinal Motility

Edward J. Hall, MA, VetMB, PhD Professor Division of Companion Animal Studies University of Bristol Bristol, England United Kingdom Dietary Sensitivity

Jean A. Hall, DVM, PhD, DACVIM Associate Professor Department of Biomedical Sciences College of Veterinary Medicine Oregon State University Corvallis, Oregon Gastric Prokinetic Agents

Bernie Hansen, DVM Associate Professor, ICU Critical Care School of Veterinary Medicine Purdue University West Lafayette, Indiana Epidural Analgesia

Stuart C. Helfand, DVM, DACVIM (Oncology and Internal Medicine) Oregon Cancer Center for Animals Oregon State University Corvallis, Oregon Hematopoietic Cytokines: The Interleukin Array

Joan C. Hendricks, VMD, PhD, DACVIM The Gilbert S. Kahn Dean of Veterinary Medicine School of Veterinary Medicine University of Pennsylvania Philadelphia, Pennsylvania Airway Management

Contributors to Evolve

xxxi

Donna M. Hertzke, DVM, PhD, DACVP Assistant Director Veterinary Diagnostic Services Marshfield Laboratories Marshfield, Wisconsin Cutaneous and Renal Glomerulopathy of Greyhound Dogs

David E. Holt, BVSc, DACVS Section Chief, Surgery Professor of Surgery, Clinical Educator Department of Clinical Studies School of Veterinary Medicine University of Pennsylvania Philadelphia, Pennsylvania Feline Constipation and Idiopathic Megacolon

Dez Hughes, BVSc, MRCVS, DACVECC Senior Lecturer in Emergency and Critical Care Royal Veterinary College University of London London, England United Kingdom Lactate Measurement: Diagnostic, Therapeutic, and Prognostic Implications

Victoria G. Jones, DVM, MS, DACVO Northwest Animal Eye Specialists Kirkland, Washington Nonulcerative Corneal Disease

Andrew J. Kaplan, DVM, DACVIM City Veterinary Care New York, New York Effects of Nonadrenal Disease on Adrenal Function Tests in Dogs

Charlotte B. Keller, DrMedVet, DACVO, DECVO Formerly Assistant Professor Department of Clinical Studies Ontario Veterinary College University of Guelph Guelph, Ontario Canada Epiphora

Lesley G. King, MVB, MRCVS, DACVECC, DACVIM School of Veterinary Medicine University of Pennsylvania Philadelphia, Pennsylvania Airway Management Colloid Osmometry

Peter P. Kintzer, DVM, DACVIM Staff Internist Department of Medicine Boston Road Animal Hospital Springfield, Massachusetts Differential Diagnosis of Hyperkalemia and Hyponatremia in Dogs and Cats

xxxii

Contributors to Evolve

Rebecca Kirby, DVM, DACVIM (Internal Medicine), DACVECC Animal Emergency Center Glendale, Wisconsin Cats Are Not Dogs in Critical Care

Mary Anna Labato, DVM, DACVIM Clinical Associate Professor Section Head, Small Animal Medicine Department of Clinical Sciences Foster Hospital for Small Animals Cummings School of Veterinary Medicine Tufts University North Grafton, Massachusetts Peritoneal Dialysis

Kenneth S. Latimer, DVM, PhD, DACVP Professor Department of Veterinary Pathology College of Veterinary Medicine University of Georgia Athens, Georgia Overview of Neutrophil Dysfunction in Dogs and Cats

Cheryl A. London, DVM, PhD, DACVIM (Oncology) Associate Professor College of Veterinary Medicine The Ohio State University Columbus, Ohio Hematopoietic Cytokines: The Myelopoietic Factors

Chris L. Ludlow, DVM, MS, DACVIM Staff Veterinarian Veterinary Internal Medicine Specialists of Kansas City Overland Park, Kansas Small Intestinal Bacterial Overgrowth

Marilena Lupu, DVM, PhD Resident in Veterinary Oncology Oregon Cancer Center for Animals Department of Clinical Sciences Oregon State University Corvallis, Oregon Hematopoietic Cytokines: The Interleukin Array

Douglass K. Macintire, DVM, MS, DACVIM, DACVECC Professor of Acute Medicine and Critical Care Department of Clinical Sciences College of Veterinary Medicine Auburn University Auburn, Alabama Bacterial Translocation: Clinical Implications and Prevention Canine Hepatozoonosis

Ruth Marrion, DVM, PhD, DACVO Staff Ophthalmologist Essex County Veterinary Specialists North Andover, Massachusetts Ulcerative Keratitis

Glenna E. Mauldin, DVM, MS, DACVIM Assistant Professor of Veterinary Oncology and Companion Animal Medicine School of Veterinary Medicine Louisiana State University Baton Rouge, Louisiana Nutritional Support of the Cancer Patient

Karrelle A. Meleo, DVM, DACVIM Senior Oncologist Veterinary Oncology Services Redmond, Washington Treatment of Insulinoma in the Dog, Cat, and Ferret

Carlos Melián, DVM, PhD Director Clinica Veterinaria Atlantico Las Palmas de Gran Canaria Spain The Incidentally Discovered Adrenal Mass

†E. Phillip Miller, DVM, MS, DABVT, DABT Formerly Director of Product Safety and Efficacy Hill’s Pet Nutrition, Inc. Topeka, Kansas Pet Food Safety

Eric Monnet, DVM, PhD, DACVS, DECVS Associate Professor, Small Animal Surgery Department of Clinical Sciences College of Veterinary Medicine and Biomedical Sciences Colorado State University Fort Collins, Colorado Thoracoscopy

Cecil P. Moore, DVM, MS, DACVO Interim Dean and Professor Department of Veterinary Medicine and Surgery College of Veterinary Medicine University of Missouri Columbia, Missouri Keratoconjunctivitis Sicca

Peter F. Moore, BVSc, PhD Professor Department of Pathology, Microbiology, and Immunology College of Veterinary Medicine University of California Davis, California Immunophenotyping in the Dog

Mark P. Nasisse, DVM, DACVO Carolina Veterinary Specialists Greensboro, North Carolina Ocular Feline Herpesvirus-1 Infection

Rhett Nichols, DVM, DACVIM Internal Medicine Consultant Antech Diagnostics Farmingdale, New York Clinical Use of the Vasopressin Analogue DDAVP for the Diagnosis and Treatment of Diabetes Insipidus †Deceased.



Contributors to Evolve

xxxiii

E. Christopher Orton, DVM, PhD, DACVS

Marc R. Raffe, DVM, MS, DACVA, DACVECC

Professor Department of Clinical Sciences Veterinary Teaching Hospital Colorado State University Fort Collins, Colorado Current Indications and Outcomes for Cardiac Surgery

Adjunct Professor Department of Clinical Sciences Colorado State University Fort Collins, Colorado Point-of-Care Laboratory Testing in the Intensive Care Unit

David L. Panciera, DVM, MS, DACVIM (SAIM)

Owner The Animal Ophthalmology Center Williamston, Michigan Exophthalmos

Professor Department of Small Animal Clinical Sciences Virginia-Maryland Regional College of Veterinary Medicine Virginia Polytechnic Institute and State University Blacksburg, Virginia Cardiovascular Complications of Thyroid Disease Complications and Concurrent Conditions Associated With Hypothyroidism in Dogs

Mark G. Papich, DVM, MS Professor of Clinical Pharmacology College of Veterinary Medicine North Carolina State University Raleigh, North Carolina Bacterial Resistance

Jennifer M. Pearson, DVM, MS, DACVIM Staff Internist Internal Medicine Department Animal Hospital Center Highlands Ranch, Colorado Diagnosis and Treatment of Parvovirus

Mark E. Peterson, DVM, DACVIM Head of Endocrinology Department of Medicine, Bobst Hospital Associate Director, Caspary Research Institute Chairman, Institute of Postgraduate Education The Animal Medical Center New York, New York Effects of Nonadrenal Disease on Adrenal Function Tests in Dogs Growth Hormone Therapy in the Dog Hyperadrenocorticism in the Ferret The Incidentally Discovered Adrenal Mass

Eric R. Pope, DVM, MS, DACVS Professor, Small Animal Surgery Ross University School of Veterinary Medicine Basseterre, St. Kitts West Indies Feline Respiratory Tract Polyps †Jeffrey Proulx, DVM Formerly Resident in Emergency and Critical Care Cummings School of Veterinary Medicine Tufts University North Grafton, Massachusetts Sodium Nitroprusside: Uses and Precautions

†Deceased.

David T. Ramsey, DVM, DACVO

John F. Randolph, DVM, DACVIM Professor of Medicine Department of Clinical Sciences College of Veterinary Medicine Cornell University Ithaca, New York Growth Hormone Therapy in the Dog

Karen L. Rosenthal, DVM, MS Director of Special Species Medicine Associate Professor Abaxis Chair of Special Species Medicine Department of Clinical Studies School of Veterinary Medicine University of Pennsylvania Philadelphia, Pennsylvania Hyperadrenocorticism in the Ferret

Linda A. Ross, DVM, MS, DACVIM (SAIM) Associate Professor Department of Clinical Sciences Cummings School of Veterinary Medicine Tufts University North Grafton, Massachusetts Peritoneal Dialysis

Philip Roudebush, DVM, DACVIM (SAIM) Director, Scientific Affairs Hill’s Pet Nutrition, Inc. Topeka, Kansas Hypoallergenic Diets for Dogs and Cats

Elke Rudloff, DVM, DACVECC Director of Education Animal Emergency Center Glendale, Wisconsin Cats Are Not Dogs in Critical Care

Charles E. Rupprecht, VMD, MS, PhD Chief, Rabies Section Centers for Disease Control and Prevention Atlanta, Georgia The Rabies Pandemic

Michael Scott, DVM, PhD, DACVP Assistant Professor College of Veterinary Medicine University of Missouri Columbia, Missouri Interpretation of Cytograms and Histograms of Erythrocytes, Leukocytes, and Platelets

xxxiv

Contributors to Evolve

Kenneth W. Simpson, BVM&S, PhD, DACVIM, DECVIM-CA

Shelly L. Vaden, DVM, PhD, Diplomate ACVIM

Associate Professor of Medicine College of Veterinary Medicine Cornell University Ithaca, New York Gastrinoma in Dogs

Professor, Internal Medicine Department of Clinical Sciences College of Veterinary Medicine North Carolina State University Raleigh, North Carolina Differentiation of Acute From Chronic Renal Failure

Patricia J. Smith, DVM, MS, PhD, DACVO

William Vernau, BSc, BVMS, DVSc, DACVP

Animal Eye Care Fremont, California Hypertensive Retinopathy

Clinical Pathologist Veterinary Medicine Pathology, Microbiology, and Immunology School of Veterinary Medicine University of California Davis, California Immunophenotyping in the Dog

Rebecca L. Stepien, DVM, MS, DACVIM (Cardiology) Clinical Associate Professor, Cardiology Department of Medical Sciences Cardiology Service Head Veterinary Teaching Hospital School of Veterinary Medicine University of Wisconsin Madison, Wisconsin Feline Congenital Heart Disease

Nancy Vincent-Johnson, DVM, MS, DACVIM Major, US Army Veterinary Command 94th Medical Detachment (VM) Fort Sam Houston San Antonio, Texas Canine Hepatozoonosis

Elizabeth A. Stone, DVM, MS, DACVS

Don R. Waldron, BS, DVM, DACVS

Professor and Head Department of Companion Animal and Special Species Medicine College of Veterinary Medicine North Carolina State University Raleigh, North Carolina Indications for Nephrectomy and Nephrotomy

Professor of Surgery Section Chief of Small Animal Surgery and Anesthesiology Virginia-Maryland Regional College of Veterinary Medicine Virginia Polytechnic Institute and State University Blacksburg, Virginia Urine Diversion by Tube Cystostomy

Alain Théon, DrMedVet, MS, DACVR

Ronald S. Walton, DVM, MS, DACVIM, DACVECC

Associate Professor Department of Veterinary Medicine Surgery and Radiological Science School of Veterinary Medicine University of California, Davis, California Diagnosis and Management of Large Pituitary Tumors in Dogs With Pituitary-Dependent Hyperadrenocorticism

Amy S. Tidwell, DVM, DACVR Associate Professor Department of Clinical Sciences Cummings School of Veterinary Medicine Tufts University North Grafton, Massachusetts Use of Computed Tomography in Cardiopulmonary Disease

Harold Tvedten, DVM, MS, PhD, DACVP Professor of Pathology and Chief of Veterinary Clinical Pathology Section Veterinary Teaching Hospital Michigan State University East Lansing, Michigan Interpretation of Cytograms and Histograms of Erythrocytes, Leukocytes, and Platelets

US Army Rocky Mountain District Veterinary Command Fort Carson, Colorado Thoracoscopy

Robert J. Washabau, VMD, PhD, DACVIM Associate Professor and Section Chief of Medicine Department of Clinical Studies School of Veterinary Medicine University of Pennsylvania Philadelphia, Pennsylvania Feline Constipation and Idiopathic Megacolon Gastric Prokinetic Agents

Wanda Wilson, BS, DVM Senior Resident, Emergency and Critical Care Animal Emergency Center and Referral Center Milwaukee, Wisconsin Cats Are Not Dogs in Critical Care

In memory of Hazel Young Bonagura, my best teacher. JDB

To my wife Liz and my son Ryan for their love and support. To my parents for helping me achieve my dreams. David C. Twedt

This page intentionally left blank

Preface

T

his new edition of Kirk’s Current Veterinary Therapy is the fourteenth version of a textbook used by generations of practicing veterinarians and veterinary students. The general format and chapter presentation of this edition should be familiar to long-time users of “CVT”. For our new readers it is my hope that you find the information in this textbook (and the related CVT website) both informative and accessible. Foremost, I hope CVT will help you provide the best possible care for your canine and feline patients. Whereas the overall format of this new edition follows the original formula outlined by Dr. Robert W. Kirk, there are also changes and enhancements. As the title suggests, the focus of most chapters is therapy of important medical diseases of dogs and cats. Current Veterinary Therapy is divided into thirteen sections and three appendices. The sections are organized by organ system, including cardiovascular, dermatologic, gastrointestinal, hematologic, neurologic and musculoskeletal, ophthalmologic, reproductive, respiratory, and urinary diseases. Multisystemic diseases are detailed in the sections covering critical care medicine, infectious diseases, oncology and hematology, and toxicology. Appendix I, Table of Common Drugs: Approximate Dosages, and the tables in Appendix II, Treatment of Parasites, have been completely revised for this edition. Of great importance is the oversight ­provided by one or more specialists who served as Consulting Editor for each of these sections. I am most grateful to these outstanding clinicians for their guidance and ­ editorial input. It is worthwhile to highlight some of the changes adopted for this edition. Foremost has been the inclusion of an Associate Editor, Dr. David Twedt. Dave is recognized worldwide as an outstanding internist, gastroenterologist, and educator. I am most appreciative of his excellent ­editorial work, and have benefitted greatly from the perspective he brought to this volume. We also recruited some outstanding new Consulting Editors for this edition, while retaining the services of some of the most respected authorities in small animal medicine. Another change involved rearranging sections. Gone is the section on Diseases of Birds and Exotic Pets. In recent years these areas have exploded in terms of knowledge and practices, as demonstrated by the proliferation of complete ­textbooks covering these subjects. After some discussion, it was decided that CVT should now concentrate on canine and feline patients. Additionally, the Special Therapy section has been eliminated and its topics moved into the most relevant sections for those treatments. The ­former Cardiopulmonary Diseases section has been reasonably divided into two sections: Cardiovascular Diseases and Respiratory Diseases.

In keeping with current and still-evolving publishing practices, we have made one major change to the fourteenth edition in the guise of a Current Veterinary Therapy website. Owners of this textbook will have ­ password access to this electronic content, which resides on the Elsevier Evolve website (http://evolve.elsevier.com/ Bonagura/Kirks/). We have included on this site chapters from the thirteenth edition that we believe are still useful to our readers. A number of these chapters have been updated by the original authors. These “still-current” chapters are organized by section along the same lines as the textbook. Additionally, the website contains an image library of figures printed in this new edition, with additional images also available in color. Website users can access an online, searchable index (citing chapters in both the current edition and CVT XIII). Appendices I-III from the textbook will also be provided in a searchable format on Evolve. Finally, we have made the decision to free up more pages for published chapters by moving some of the appendices to the Evolve website. Many of these tables relate to reference values, which we realize are often instrument and laboratory specific. Nevertheless, the interested reader will find a number of useful tables of laboratory results and values in the appendices on the website. The development of a CVT website also provides an avenue for disseminating information to readers between editions, for example, should issues arise related to drug use or ­ dosage (a real concern with many extra-label uses of drugs in ­veterinary practice). Current Veterinary Therapy XIV contains 286 published chapters and three appendices, with contributions by hundreds of authors active in their respective clinical specialties. I am indebted to these individuals for providing concise and clinically useful chapters for the current edition. We have tried to maintain the historical format of Kirk’s chapters that considers the salient clinical ­features of a disease or disorder, the basis for rational therapy, and clear and practical pointers for treatment, while also addressing pending innovations in therapy. As stated above, most chapters are directed toward management of a specific condition. Others concentrate on important principles of therapy or general management approaches to diseases of dogs and cats. With the rapid development of knowledge across our diverse profession, we have undoubtedly omitted some topics. Treatment of some of these may have changed little in the past 5 years. Others are simply beyond our scope (or page allotment) or may be better covered ­elsewhere. This is especially true of specific surgical procedures, a subject area in which CVT provides only limited guidance. The fastest way to find information in Current Veterinary Therapy is through the index. The index is organized to xxxvii

xxxviii

Preface

emphasize diseases based on anatomic and physiologic disorders and is extensively cross-referenced. Using either the index printed in the textbook or the online version on the website, the reader should be able to locate a ­concise chapter detailing the most important medical problems of dogs and cats. Many readers familiar with the CVT format will probably head straight for the individual sections’ tables of content to peruse the section contents. Related chapters located on the Evolve website are also listed there. As some subjects “overlap” individual ­sections, we have made every attempt to cross-index information in chapters throughout the book. Current Veterinary Therapy is written for both the veterinary practitioner and the veterinary student. It is my hope that CVT will be discovered by students who will later find its contents an asset to their professional work. I am always grateful to receive comments from readers, including any concerns about possible errors or omissions. Ideas designed to improve this textbook are most welcome. As I have written previously, I have tried to maintain CVT on the course first set by Dr. Kirk. I remain most appreciative of your acceptance of previous editions and this new one.

Acknowledgments I would like to acknowledge a number of individuals. I am most thankful to the veterinarians and scientists who have contributed to this edition and to the expertise and

oversight of our Consulting Editors. Bringing Dr. David Twedt on board has been very helpful, and the book is far better for his efforts. I am especially appreciative of Jolynn Gower, Managing Editor at Elsevier. Without Jolynn’s sustained efforts and encouragement, this edition would still be on my desktop (real and electronic). Publisher Penny Rudolph has provided helpful oversight and counsel throughout this endeavor, and I appreciate her patient support. Karen Rehwinkel, Senior Project Manager at Elsevier, has most ably handled the hundreds of manuscripts, electronic documents, authors’ information, and page proofs to somehow create this volume. Liz Fathman, my former editor at Elsevier, was most helpful in getting this project started. Others at Elsevier, with whom I have not worked directly, have been important in creating this textbook, and I extend my deepest appreciation to them. Special thanks are extended to Debra Primovic, DVM, for indexing this and the previous volume of CVT. John D. Bonagura, DVM Columbus, Ohio

Contents Section I Critical Care Nishi Dhupa

1 Shock, 2 Annie Malouin, Deborah Silverstein



2 Acute Pain Management, 9 Andrea L. Looney



3 Nutrition in Critical Care, 18 Daniel L. Chan



4 Antiplatelet and Anticoagulant Therapy, 24 Marilyn Dunn, Marjory B. Brooks



5 Cardiopulmonary Cerebral Resuscitation, 28 Gretchen L. Schoeffler



6 Traumatic Brain Injury, 33 Daniel J. Fletcher, Curtis W. Dewey



7 Vascular Access Techniques, 38 James S. Wohl, Marion B. Tefend



8 Pacing in the Critical Care Setting, 43 Anna R.M. Gelzer, Marc S. Kraus



9 Fluid Therapy, 48 Stephen P. DiBartola, Shane W. Bateman

10 Acid-Base Disorders, 54 Helio Autran de Morais, Stephen P. DiBartola 11 Colloid Fluid Therapy, 61 Elke Rudloff, Rebecca Kirby 12 A  cute Abdomen: Evaluation and Emergency Treatment, 67 F. Anthony Mann 13 Drainage Techniques for the Septic Abdomen, 72 Adrienne Bentley, David E. Holt 14 Gastric Dilation-Volvulus, 77 Karol A. Mathews 15 Emergency Management of Open Fractures, 83 Robert J. McCarthy 16 Thoracic Trauma, 86 Scott P. Shaw 17 Intravenous Anesthetic and Analgesic Techniques, 88 Thomas K. Day Section II Toxicologic Diseases Michael J. Murphy 18 Toxin Exposures in Small Animals, 92 Lynn R. Hovda

19 T  oxin Exposures and Treatments: A Survey of Practicing Veterinarians, 95 Kelly Hall 20 R  eporting an Adverse Drug Reaction to the Food and Drug Administration, 99 Lynn O. Post 21 Sources of Help for Toxicosis, 104 Michael J. Murphy 22 Small Animal Poisoning: Additional Considerations Related to Legal Claims, 105 Michael J. Murphy 23 Urban Legends of Toxicology: Facts and Fiction, 109 Frederick W. Oehme, William R. Hare 24 Toxicosis Treatments, 112 Kelly Hall 25 Rodenticide Toxicoses, 117 Michael J. Murphy 26 Insecticide Toxicoses, 119 Patricia A. Talcott 27 Parasiticide Toxicoses: Avermectins, 125 Wilson K. Rumbeiha 28 Lead Toxicosis in Small Animals, 127 Sharon M. Gwaltney-Brant 29 Automotive Toxins, 130 Karyn Bischoff 30 Nicotine Toxicosis, 135 Wayne Spoo 31 Recently Recognized Animal Toxicants, 138 Jocelyn A. Mason, Safdar A. Khan, Sharon M. Gwaltney-Brant 32 Human Drugs of Abuse, 144 Petra A. Volmer 33 T  oxicology of Veterinary and Human Estrogen and Progesterone Formulations in Dogs, 147 Margaret V. Root Kustritz 34 Herbal Hazards, 149 Elizabeth A. Hausner, Robert H. Poppenga 35 Aflatoxicosis in Dogs, 156 Karyn Bischoff, Tam Garland 36 Nephrotoxicants, 159 Wilson K. Rumbeiha, Michael J. Murphy 37 Food Toxicoses in Small Animals, 165 Michael J. Murphy, Julie Churchill

xxxix

xl

Contents

Section III Endocrine and Metabolic Diseases Mark E. Peterson 38 Interpretation of Endocrine Diagnostic Test Results for Adrenal and Thyroid Disease, 170 Robert J. Kemppainen, Ellen N. Behrend 39 Medical Treatment of Feline Hyperthyroidism, 175 Lauren A. Trepanier

58 Nonregenerative Anemias, 272 Douglas J. Weiss 59 v  on Willebrand’s Disease and Other Hereditary Coagulopathies, 277 Anthony P. Carr, Belle M. Nibblett, David L. Panciera 60 Thrombocytopenia, 281 Jennifer A. Neel, Adam J. Birkenheuer, Carol B. Grindem

40 Radioiodine for Feline Hyperthyroidism, 180 Mark E. Peterson

61 D  isseminated Intravascular Coagulation: Diagnosis and Management, 287 Elke Rudloff, Rebecca Kirby

41 Hypothyroidism, 185 J. Catharine R. Scott-Moncrieff

62 Platelet Dysfunction, 292 Marjory B. Brooks, James L. Catalfamo

42 Obesity, 191 Angela L. Lusby, Claudia A. Kirk

63 Clinical Trials in Veterinary Oncology, 297 Chand Khanna, Melissa Paoloni

43 Canine Diabetes Mellitus, 196 William E. Monroe

64 Collection of Specimens for Cytology, 301 Kenita S. Rogers

44 Feline Diabetes Mellitus, 199 Jacquie S. Rand

65 Anticancer Drugs and Protocols: Traditional Drugs, 305 Antony S. Moore, Angela E. Frimberger

45 Diet and Diabetes, 204 Debra L. Zoran

66 Anticancer Drugs: New Drugs, 311 Douglass H. Thamm, David M. Vail

46 Diabetic Monitoring, 209 Claudia E. Reusch

67 Radiotherapy: Basic Principles and Indications, 315 Eric M. Green

47 Complicated Diabetes Mellitus, 214 Deborah S. Greco

68 Surgical Oncology Principles, 320 James P. Farese

48 A  typical and Subclinical Hyperadrenocorticism, 219 J. Catharine R. Scott-Moncrieff

69 Canine Soft-Tissue Sarcomas, 324 Tania A. Banks, Julius M. Liptak

49 Canine Hyperadrenocorticism, 224 Ian Ramsey, Reto Neiger 50 Adrenal Insufficiency in Critical Illness, 228 Jennifer E. Prittie 51 Hypoadrenocorticism, 231 Peter P. Kintzer, Mark E. Peterson 52 Idiopathic Feline Hypercalcemia, 236 Dennis J. Chew, Patricia A. Schenck 53 Treatment of Hypoparathyroidism, 241 Dennis J. Chew, Larry A. Nagode, Patricia A. Schenck 54 C  anine Hypercalcemia and Primary Hyperparathyroidism, 247 Edward C. Feldman, Richard W. Nelson Section IV Oncology and Hematology Douglass H. Thamm

70 Canine Hemangiosarcoma, 328 Craig A. Clifford, Louis-Phillippe de Lorimier 71 Feline Vaccine-Associated Sarcomas, 332 Mattie J. Hendrick, A. Elizabeth Hershey 72 Canine Lymphoma, 336 Susan E. Lana, Anne Avery 73 Feline Gastrointestinal Lymphoma, 340 Keith P. Richter 74 Paraneoplastic Hypercalcemia, 343 David M. Vail 75 Histiocytic Disease Complex, 348 Peter F. Moore, Verena K. Affolter 76 Nasal Tumors, 352 Lisa J. Forrest 77 Pulmonary Neoplasia, 354 Kevin A. Hahn, Sandra M. Axiak

55 Immunosuppressive Agents, 254 Clare R. Gregory

78 Osteosarcoma, 358 Nicole P. Ehrhart, Timothy M. Fan

56 Blood-Typing and Crossmatching, 260 Urs Giger

79 Mammary Cancer, 363 Carolyn J. Henry

57 Immune-Mediated Hemolytic Anemia, 266 Ellen Miller

80 Urinary Bladder Cancer, 369 Deborah W. Knapp



Contents

81 Mast Cell Tumor, 373 Cheryl A. London 82 Malignant Melanoma, 378 Philip J. Bergman 83 Anal Sac Tumors, 382 Ruthanne Chun Section V

Dermatologic Diseases

Craig E. Griffin, Wayne S. Rosenkrantz 84 Cyclosporine Use in Dermatology, 386 Craig E. Griffin 85 Interferons, 389 Toshiroh Iwasaki 86 Avermectins in Dermatology, 390 Amanda Burrows 87 Hypoallergenic Diets: Principles in Therapy, 395 Hilary A. Jackson 88 Pentoxifylline, 397 Rosanna Marsella 89 Glucocorticoids in Veterinary Dermatology, 400 Candace A. Sousa 90 Feline Pruritus Therapy, 405 Sophie Gilbert

xli

104 T  herapy of Malassezia Infections and Malassezia Hypersensitivity, 453 Daniel O. Morris 105 Treatment of Dermatophytosis, 457 Douglas J. DeBoer, Karen A. Moriello 106 N  onneoplastic Nodular Histiocytic Diseases of the Skin, 462 Verena K. Affolter, Catherine A. Outerbridge 107 Diseases of the Anal Sac, 465 Rusty Muse 108 Acral Lick Dermatitis, 468 John M. MacDonald, Dino M. Bradley Section VI Gastrointestinal Diseases David C. Twedt 109 Feline Caudal Stomatitis, 476 Linda J. DeBowes 110 Oropharyngeal Dysphagia, 479 G. Diane Shelton 111 Esophagitis, 482 Michael D. Willard, Elizabeth W. Carsten 112 Canine Megaesophagus, 486 Beth M. Johnson, Robert C. DeNovo, Erick A. Mears

91 Shampoo Therapy, 410 Wayne S. Rosenkrantz

113 G  astric Helicobacter spp. and Chronic Vomiting in Dogs, 492 Michael S. Leib, Robert B. Duncan

92 Allergen-Specific Immunotherapy, 415 Craig E. Griffin, John M. MacDonald

114 Gastric Ulceration, 497 Reto Neiger

93 Topical Immunomodulators, 420 Joel D. Griffies

115 Inflammatory Bowel Disease, 501 Alexander J. German

94 House Dust Mites and Their Control, 425 Wayne S. Rosenkrantz

116 Tylosin-Responsive Diarrhea, 506 Elias Westermarck

95 Topical Therapy of Otitis Externa, 428 Colleen Mendelsohn

117 Tritrichomonas, 509 Jody L. Gookin

96 S  ystemic Therapy for Otitis Externa and Media, 434 Lynette K. Cole

118 Protein-Losing Enteropathy, 512 Lisa E. Moore

97 Ear-Flushing Techniques, 436 Dawn Logas

119 Chronic Colitis, 515 Nolie K. Parnell

98 Feline Demodicosis, 438 Karin M. Beale, Daniel O. Morris

120 Canine Ulcerative Colitis, 521 Kenneth W. Simpson

99 Feline Viral Skin Disease, 441 Rudayna Ghubash

121 Flatulence, 523 Philip Roudebush

100 Canine Papillomaviruses, 443 Masahiko Nagata

122 Anal-Rectal Disease, 527 Craig B. Webb

101 Pyotraumatic Dermatitis (‘‘Hot Spots”), 446 Wayne S. Rosenkrantz

123 Exocrine Pancreatic Insufficiency in Dogs, 531 Maria Wiberg

102 Methicillin-Resistant Canine Pyoderma, 449 Carlo Vitale

124 Canine Pancreatic Disease, 534 Jörg M. Steiner

103 Sebaceous Adenitis, 451 Edmund J. Rosser, Jr.

125 Feline Exocrine Pancreatic Disease, 538 David A. Williams

xlii

Contents

126 Diagnostic Approach to Hepatobiliary Disease, 543 Cynthia R.L. Webster, Johanna C. Cooper

148 Chronic Bronchitis and Asthma in Cats, 650 Philip Padrid

127 E  valuation of Elevated Serum Alkaline Phosphatase in the Dog, 549 Anthony T. Gary, David C. Twedt

149 Bacterial Pneumonia, 658 Richard B. Ford

128 Hepatic Support Therapy, 554 Bente Flatland 129 Copper-Associated Chronic Hepatitis, 557 Gaby Hoffman, Jan Rothuizen 130 Ursodeoxycholic Acid Therapy, 563 Cynthia R.L. Webster 131 Drug-Associated Liver Disease, 566 Mark E. Hitt 132 Feline Hepatic Lipidosis, 570 Kathleen M. Holan 133 Feline Inflammatory Liver Disease, 576 David C. Twedt, P. Jane Armstrong 134 Portosystemic Shunts, 581 Karen M. Tobias 135 Canine Biliary Mucocele, 587 Heidi A. Hottinger 136 Esophageal Feeding Tubes, 589 Howard B. Seim, III Section VII Respiratory Diseases Eleanor C. Hawkins

150 Noncardiogenic Pulmonary Edema, 663 Kenneth J. Drobatz, H. Mark Saunders 151 Respiratory Parasites, 666 Robert G. Sherding 152 Interstitial Lung Diseases, 672 Brendan M. Corcoran 153 Pleural Effusion, 675 Eleanor C. Hawkins, Theresa W. Fossum 154 Pneumothorax, 685 Amy K. Valentine, Daniel D. Smeak 155 Pulmonary Thromboembolism, 689 Susan G. Hackner 156 Pulmonary Hypertension, 697 Rosemary A. Henik Section VIII Cardiovascular Diseases John D. Bonagura 157 N  utritional Management of Heart Disease, 704 Lisa M. Freeman 158 Syncope, 709 Marc S. Kraus, Clay A. Calvert

137 Oxygen Therapy, 596 Dennis T. Crowe, Jr.

159 Systemic Hypertension, 713 Rebecca L. Stepien, Rosemary A. Henik

138 Ventilator Therapy, 603 Shane W. Bateman, Elizabeth O’Toole

160 Permanent Cardiac Pacing in Dogs, 717 Mark A. Oyama, D. David Sisson

139 Rhinitis in the Dog, 609 Ned F. Kuehn

161 A  ssessment and Treatment of Supraventricular Tachyarrhythmias, 722 Kathy N. Wright

140 Rhinitis in the Cat, 616 Lynelle R. Johnson 141 B  rachycephalic Upper Airway Syndrome in Dogs, 619 Eric R. Pope, Gheorge M. Constantinescu 142 Nasopharyngeal Disorders, 622 Geraldine B. Hunt, Susan F. Foster 143 Laryngeal Diseases, 627 Catriona M. MacPhail, Eric Monnet 144 Medical Management of Tracheal Collapse, 630 Michael E. Herrtage 145 Intraluminal Stenting for Tracheal Collapse, 635 Chick W.C. Weisse 146 Chronic Bronchitis in Dogs, 642 Lynelle R. Johnson 147 B  ordetella bronchiseptica: Beyond Kennel Cough, 646 Richard B. Ford

162 Ventricular Arrhythmias in Dogs, 727 N. Sydney Moïse, Anna R.M. Gelzer, Marc S. Kraus 163 Feline Cardiac Arrhythmias, 731 Etienne Côté, Neil K. Harpster 164 Cardioversion, 739 Janice M. Bright, Julie Martin 165 Patent Ductus Arteriosus, 744 Matthew W. Miller, Sonya G. Gordon 166 Ventricular Septal Defect, 748 Rebecca E. Gompf, John D. Bonagura 167 Pulmonic Stenosis, 752 Amara Estrada 168 Subaortic Stenosis, 757 R. Lee Pyle, Jonathan A. Abbott 169 Tricuspid Valve Dysplasia, 762 Darcy B. Adin



Contents

170 Mitral Valve Dysplasia, 765 Barret J. Bulmer

191 Acute Renal Failure, 879 Linda Ross

171 Management of Heart Failure in Dogs, 769 Bruce W. Keene, John D. Bonagura

192 C  hronic Kidney Disease: Staging and Management, 883 Jonathan Elliott, A.D.J. Watson

172 Chronic Valvular Heart Disease in Dogs, 780 John E. Rush 173 Infective Endocarditis, 786 Kristin A. MacDonald 174 Dilated Cardiomyopathy in Dogs, 792 Daniel F. Hogan, Henry W. Green, III 175 Cardiomyopathy in Boxer Dogs, 797 Kathryn M. Meurs, Alan W. Spier 176 Cardiomyopathy in Doberman Pinschers, 800 Clay A. Calvert, Kathryn M. Meurs 177 Myocarditis, 804 Karsten E. Schober 178 M  anagement of Feline Myocardial Disease, 809 Virginia Luis Fuentes 179 Right Ventricular Cardiomyopathy in Cats, 815 Philip R. Fox 180 Arterial Thromboembolism in Cats, 819 Anthony H. Tobias, Deborah M. Fine 181 Pericardial Effusion, 825 O. Lynne Nelson, Wendy A. Ware 182 Feline Heartworm Disease, 831 Clarke E. Atkins 183 Canine Heartworm Disease, 837 Matthew W. Miller, Sonya G. Gordon Section IX Urinary Diseases India F. Lane 184 M  anaging the Patient with Polyuria and Polydipsia, 844 Katharine F. Lunn 185 Interpreting and Managing Crystalluria, 850 Joseph W. Bartges, Claudia A. Kirk 186 Diagnostic Approach to Acute Azotemia, 855 Jennifer E. Stokes 187 Proteinuria: Implications for Management, 860 Gregory F. Grauer 188 Glomerular Disease, 863 Shelly L. Vaden, Cathy A. Brown 189 M  easuring Glomerular Filtration Rate: Practical Use of Clearance Tests, 868 Sherry Lynn Sanderson 190 E  vidence-Based Management of Chronic Kidney Disease, 872 David J. Polzin, Carl A. Osborne, Sheri Ross

xliii

193 Calcitriol, 892 David J. Polzin, Sherri Ross, Carl A. Osborne 194 Hemodialysis, 896 Catherine E. Langston 195 Renal Transplantation, 901 Christopher A. Adin 196 G  astrostomy Tube Feeding in Kidney Disease, 906 Denise A. Elliott 197 Systemic Hypertension in Renal Disease, 910 Mark J. Acierno 198 Treatment of Anemia in Renal Failure, 914 Marie E. Kerl, Catherine E. Langston 199 Uncomplicated Urinary Tract Infection, 918 Mary Anna Labato 200 Multidrug-Resistant Urinary Tract Infection, 921 Jeanne A. Barsanti 201 Cancer and the Kidney, 925 Barrak M. Pressler 202 Management of Feline Ureteroliths, 931 Andrew E. Kyles, Jodi L. Westropp 203 Incomplete Urolith Removal: Prevention, Detection, and Correction, 936 Jody P. Lulich, Carl A. Osborne `204 Laser Lithotripsy for Uroliths, 940 Larry G. Adams, Jody P. Lulich 205 M  anagement of Feline Nonobstructive Idiopathic Cystitis, 944 John M. Kruger, Carl A. Osborne 206 Urethral Obstruction in Cats, 951 Kenneth J. Drobatz 207 U  rinary Incontinence and Micturition Disorders: Pharmacologic Management, 955 India F. Lane, Jodi L. Westropp 208 U  rinary Incontinence: Treatment With Injectable Bulking Agents, 960 Julie K. Byron, Dennis J. Chew, Mary A. McLoughlin 209 Interventional Radiology in Urinary Diseases, 965 Chick W.C. Weisse, Allyson C. Berent Section X Reproductive Diseases Margaret V. Root Kustritz 210 Breeding Management of the Bitch, 974 Gary C.W. England, Marco Russo

xliv

Contents

211 U  se of Vaginal Cytology and Vaginal Cultures for Breeding Management and Diagnosis of Reproductive Tract Disease, 980 Beverly J. Purswell 212 E  ndoscopic Transcervical Insemination, 983 Marion S. Wilson 213 Pregnancy Loss in the Bitch, 986 Joni L. Freshman 214 False Pregnancy in the Bitch, 990 Dana R. Bleifer 215 Dystocia Management, 992 Autumn P. Davidson 216 Canine Postpartum Disorders, 999 Michelle A. Kutzler 217 N  utrition in the Bitch During Pregnancy and Lactation, 1003 David A. Dzanis 218 Pyometra, 1008 Frances O. Smith

Section XI Neurologic and Musculoskeletal Diseases Rodney S. Bagley 231 Treatment of Status Epilepticus, 1062 Michael Podell 232 N  ew Maintenance Anticonvulsant Therapies for Dogs and Cats, 1066 Curtis W. Dewey 233 T  reatment of Primary Central Nervous System Inflammation (Encephalitis and Meningitis), 1070 Andrea Tipold 234 Treatment of Cerebrovascular Disease, 1074 Laurent S. Garosi, Simon R. Platt 235 Treatment of Intracranial Tumors, 1078 Jill Narak, Todd W. Axlund, Annette N. Smith 236 Diagnosis and Treatment of Atlantoaxial Subluxation, 1083 Beverly K. Sturges

219 Vaginitis, 1010 Margaret V. Root Kustritz

237 T  reatment of Canine Cervical Spondylomyelopathy: A Critical Review, 1088 Annie V. Chen, Rodney S. Bagley

220 S  urgical Repair of Vaginal Anomalies in the Bitch, 1012 Roberto E. Novo

238 T  reatment of Degenerative Lumbosacral Stenosis, 1094 Daniel G. Hicks, Rodney S. Bagley

221 Early-Age Neutering in the Dog and Cat, 1019 Lisa M. Howe

239 Vestibular Disease of Dogs and Cats, 1097 Rodney S. Bagley

222 Estrus Suppression in the Bitch, 1024 Patrick Concannon

240 T  reatment of Canine Chiari-Like Malformation and Syringomyelia, 1102 Clare Rusbridge, Curtis W. Dewey

223 Canine Pregnancy Termination, 1031 Bruce E. Eilts 224 Inherited Disorders of the Reproductive Tract in Dogs and Cats, 1034 Vicki N. Meyers-Wallen 225 Ovarian Remnant Syndrome in Cats, 1040 Margaret V. Root Kustritz 226 Pregnancy Loss in the Queen, 1041 Claudia J. Baldwin 227 M  edical Treatment of Benign Prostatic Hypertrophy and Prostatitis in Dogs, 1046 Kaitkanoke Sirinarumitr 228 A  spermia/Oligozoospermia Caused by Retrograde Ejaculation in the Dog, 1049 Stefano Romagnoli, Giovanni Majolino 229 Intermittent Erection of the Penis in Castrated Male Dogs, 1053 Margaret V. Root Kustritz 230 M  ethods and Availability of Tests for Hereditary Disorders of Dogs, 1054 Edward E. (Ned) Patterson

241 T  reatment of Autoimmune Myasthenia Gravis, 1108 G. Diane Shelton 242 T  reatment of Myopathies and Neuropathies, 1111 G. Diane Shelton 243 T  reatment of Supraspinatus Tendon Disorders in Dogs, 1117 Boel A. Fransson 244 M  edical Treatment of Coxofemoral Joint Disease, 1120 Denis J. Marcellin-Little 245 T  reatment of Animals With Spinal and Musculoskeletal Pain, 1126 Joan R. Coates 246 P  hysical Therapy and Rehabilitation of Neurologic Patients, 1131 Darryl L. Millis 247 Hypokalemic Myopathy in Cats, 1136 Boyd R. Jones



Contents

Section XII Ophthalmic Diseases David J. Maggs 248 Pearls of the Ophthalmic Examination, 1140 David J. Maggs

269 Leptospirosis, 1237 Kenneth R. Harkin 270 Bartonellosis, 1241 Edward B. Breitschwerdt

249 Ocular Pharmacology, 1145 Daniel A. Ward

271 C  anine and Feline Hemotropic Mycoplasmosis, 1245 Séverine Tasker

250 Ocular Immunotherapy, 1149 Steven R. Hollingsworth

272 Canine Anaplasma Infection, 1249 Leah A. Cohn, Stephanie J. Kottler

251 Ocular Neoplasia, 1153 Bradford J. Holmberg, Michael S. Kent

273 American Leishmaniasis, 1252 Gregory C. Troy

252 Corneal Colors As a Diagnostic Aid, 1158 David J. Maggs

274 Toxoplasmosis, 1254 Michael R. Lappin

253 Differential Diagnosis of Blindness, 1163 Holly L. Hamilton, Susan A. McLaughlin

275 Pneumocystosis, 1258 Remo Lobetti

254 Differential Diagnosis of Anisocoria, 1168 Nancy B. Cottrill

276 Feline Cytauxzoonosis, 1261 J. Paul Woods

255 Differential Diagnosis of the Red Eye, 1175 Diane V.H. Hendrix

277 Systemic Fungal Infections, 1265 Rance K. Sellon, Alfred M. Legendre

256 Diseases of the Eyelids and Periocular Skin, 1178 Catherine A. Outerbridge, Steven R. Hollingsworth

278 Pythiosis and Lagenidiosis, 1268 Amy M. Grooters

257 Feline Chlamydiosis, 1185 Jane E. Sykes

279 Canine Vaccination Guidelines, 1272 Richard B. Ford

258 Antiviral Therapy for Feline Herpesvirus, 1188 David J. Maggs

280 Feline Vaccination Guidelines, 1275 Richard B. Ford

259 Episcleritis and Scleritis in Dogs, 1190 Anna R. Deykin

281 F  eline Leukemia Virus and Feline Immunodeficiency Virus, 1278 Katrin Hartmann

260 Q  ualitative Tear Film Disturbances of Dogs and Cats, 1193 Christine C. Lim

282 Feline Calicivirus Infection, 1284 Jane E. Sykes

261 Nonhealing Corneal Erosions in Dogs, 1197 Ellison Bentley

283 Babesiosis, 1288 Adam J. Birkenheuer

262 Anterior Uveitis in Dogs and Cats, 1200 Cynthia C. Powell

284 Canine Influenza, 1291 Gabriele A. Landolt, Katharine F. Lunn

263 Feline Glaucoma, 1207 Paul E. Miller

285 F  eline Infectious Peritonitis: Therapy and Prevention, 1295 Diane D. Addie, Takuo Ishida

264 Retinal Detachment, 1215 Patricia J. Smith Section XIII Infectious Diseases Rance K. Sellon 265 Hospital-Acquired Bacterial Infections, 1222 Scott P. Shaw 266 Rational Empiric Antimicrobial Therapy, 1225 Patricia M. Dowling 267 R  ational Use of Glucocorticoids in Infectious Disease 1230 Adam Mordecai, Rance K. Sellon 268 Canine Brucellosis, 1234 Autumn P. Davidson

286 Control of Viral Diseases in Catteries, 1299 Diane D. Addie Appendices Appendix I

 able of Common Drugs: T Approximate Dosages, 1307 Mark G. Papich

Appendix II

Treatment of Parasites, 1336 Cliff Monahan

Appendix III

 AFCO Dog and Cat Food Nutrient A Profiles, 1338 David A. Dzanis



xlv

CVT XIII Content on Evolve Section I Critical Care Bacterial Translocation: Clinical Implications and Prevention Douglass K. Macintire Cats Are Not Dogs in Critical Care Rebecca Kirby Elke Rudloff Wanda Wilson Colloid Osmometry Lesley G. King Epidural Analgesia Bernie Hansen Lactate Measurement: Diagnostic, Therapeutic, and Prognostic Implications Dez Hughes Microenteral Nutrition Jennifer J. Devey Dennis T. Crowe, Jr. Point-of-Care Laboratory Testing in the Intensive Care Unit Marc R. Raffe Leah S. Faudskar Section II Toxicologic Diseases Pet Food Safety †E. Phillip Miller Section III Endocrine and Metabolic Diseases Clinical Use of the Vasopressin Analogue DDAVP for the Diagnosis and Treatment of Diabetes Insipidus Rhett Nichols Complications and Concurrent Conditions Associated With Hypothyroidism in Dogs David L. Panciera Diagnosis and Management of Large Pituitary Tumors in Dogs With Pituitary-Dependent Hyperadrenocorticism Marielle Goossens Alain Théon Edward C. Feldman Differential Diagnosis of Hyperkalemia and Hyponatremia in Dogs and Cats Peter P. Kintzer Effects of Nonadrenal Disease on Adrenal Function Tests in Dogs Andrew J. Kaplan Mark E. Peterson †Deceased

xlvi

Growth Hormone Therapy in the Dog John F. Randolph Mark E. Peterson Hyperadrenocorticism in the Ferret Karen L. Rosenthal Mark E. Peterson The Incidentally Discovered Adrenal Mass Carlos Melián Mark E. Peterson The Kidney and Hyperthyroidism Stephen P. DiBartola Scott A. Brown Treatment of Insulinoma in the Dog, Cat, and Ferret Karrelle A. Meleo Elaine R. Caplan Treatment of Non–Insulin-Dependent Diabetes Mellitus in Cats Using Oral Hypoglycemic Agents Deborah S. Greco Section IV Oncology and Hematology Disorders of Feline Red Blood Cells Mary M. Christopher Hematopoietic Cytokines: The Interleukin Array Stuart C. Helfand Marilena Lupu Hematopoietic Cytokines: The Myelopoietic Factors Cheryl A. London Hereditary and Acquired Immunodeficiency Diseases Peter J. Felsburg Hereditary Erythrocyte Disorders Urs Giger Immunophenotyping in the Dog Peter F. Moore Verena K. Affolter William Vernau Interpretation of Cytograms and Histograms of Erythrocytes, Leukocytes, and Platelets Harold Tvedten Michael Scott G. Daniel Boon Multidrug Resistance Philip J. Bergman Neutrophil Dysfunction in Dogs and Cats Kenneth S. Latimer Nutritional Support of the Cancer Patient Glenna E. Mauldin Section V

Dermatologic Diseases

Hypoallergenic Diets for Dogs and Cats Philip Roudebush



CVT XIII Content on Evolve

Section VI Gastrointestinal Diseases Assessment of Gastrointestinal Motility F. J. Allan W. Grant Guilford Diagnosis and Treatment of Parvovirus Jennifer M. Pearson Leah A. Cohn Dietary Sensitivity Edward J. Hall Feline Constipation and Idiopathic Megacolon Robert J. Washabau David E. Holt Gastric Prokinetic Agents Jean A. Hall Robert J. Washabau Gastrinoma in Dogs Kenneth W. Simpson Hepatoportal Microvascular Dysplasia Sharon A. Center Small Intestinal Bacterial Overgrowth Chris L. Ludlow Deborah J. Davenport Section VII Respiratory Diseases Airway Management Joan C. Hendricks Lesley G. King Feline Respiratory Tract Polyps Eric R. Pope Gheorge M. Constantinescu Thoracoscopy Ronald S. Walton Eric Monnet Section VIII Cardiovascular Diseases Cardiovascular Complications of Thyroid Disease David L. Panciera Current Indications and Outcomes for Cardiac Surgery E. Christopher Orton Feline Congenital Heart Disease Rebecca L. Stepien Helio Autran de Morais Sodium Nitroprusside: Uses and Precautions †Jeffrey Proulx Nishi Dhupa Use of Computed Tomography in Cardiopulmonary Disease Amy S. Tidwell Section IX Urinary Diseases Cutaneous and Renal Glomerulopathy of Greyhound Dogs Laine A. Cowan Donna M. Hertzke Differentiation of Acute From Chronic Renal Failure Shelly L. Vaden Indications for Nephrectomy and Nephrotomy Elizabeth A. Stone Jody L. Gookin †Deceased.

Peritoneal Dialysis Lisa A. Dzyban Mary Anna Labato Linda A. Ross Urine Diversion by Tube Cystostomy Don R. Waldron Section X Reproductive Diseases No content on the Evolve website at this time. Section XI Neurologic and Musculoskeletal Diseases No content on the Evolve website at this time. Section XII Ophthalmic Diseases Diagnosis and Treatment of Canine Conjunctivitis Brian C. Gilger Epiphora Charlotte B. Keller Exophthalmos David T. Ramsey Hypertensive Retinopathy Patricia J. Smith Keratoconjunctivitis Sicca Cecil P. Moore Elizabeth A. Giuliano Nonulcerative Corneal Disease Victoria G. Jones Ocular Emergencies Tony Glover Ocular Feline Herpesvirus-1 Infection Mark P. Nasisse Ulcerative Keratitis Ruth M. Marrion Section XIII Infectious Diseases Bacterial Resistance Mark G. Papich Canine Hepatozoonosis Douglass K. Macintire Nancy Vincent-Johnson Ocular Manifestations of Systemic Diseases Brian C. Gilger The Rabies Pandemic Cherie L. Drenzek Charles E. Rupprecht Ticks as Vectors of Companion Animal Diseases Sidney A. Ewing Why Are Infectious Diseases Emerging? Edward B. Breitschwerdt Steven W. Dow

xlvii

xlviii

CVT XIII Content on Evolve

Appendices* Appendix IV

Canine and Feline Reference Values

Appendix V

Hematology—Coulter S Plus IV with Manual Differential Counts

Appendix VI

Hematology—Technicon H-1 Hematology Analyzer

Appendix VII

Système International (SI) Units in Hematology

Appendix VIII

Hematology—Manual or Semiautomated Methods

Appendix IX

Canine Hematology (Means) at Different Ages—Manual or Semiautomated Methods

Appendix X

Canine Hematology (Means and Ranges) with Different Ages and Genders—Manual or Semiautomated Methods

Appendix XI

Canine Hematology at Different Ages

Appendix XII

Effects of Pregnancy and Lactation on Canine Hematology (Means)

Appendix XIII

Relative Distribution of Cell Types in Canine Bone Marrow

Appendix XIV

Feline Hematology (Means and Ranges) with Different Ages and Genders—Manual or Semiautomated Methods

Appendix XV

Feline Hematology (Means) at Different Ages

Appendix XVI

Effects of Pregnancy and Lactation on Feline Hematology (Means)

Appendix XVII

Relative Distribution of Cell Types in Feline Bone Marrow

Appendix XVIII

Clinical Chemistry—Hitachi 911

Appendix XIX

Clinical Chemistry—Selected Manual Procedures

Appendix XX

Système International (SI) Units in Clinical Chemistry

*Appendices I-III in this book are also available on Evolve. Appendices IV-XL were originally edited by Robert M. Jacobs, DVM, PhD, DACVP; Professor, Department of Pathobiology, Ontario Veterinary College, University of Guelph, Guelph, Ontario, Canada.

Appendix XXI

Clinical Chemistry—Test Characteristics for Analytes Determined on the Hitachi 911

Appendix XXII

Interferences Caused by Lipid, Bilirubin, and Hemoglobin for Analytes Determined on the Hitachi 911

Appendix XXIII

Serum Protein Fractions

Appendix XXIV

Serum Iron and Iron-Binding Capacities in Iron-Deficient and Normal Dogs

Appendix XXV

Serum Immunoglobulin Concentrations of Normal Beagle Dogs at Various Ages

Appendix XXVI

Acid-Base and Blood Gases

Appendix XXVII Coagulation Screening Tests Appendix XXVIII Specific Coagulation Tests Appendix XXIX

Quantitative Tests of Gastrointestinal Function

Appendix XXX

Tests of the Endocrine System

Appendix XXXI

Système International (SI) Units for Hormone Assays

Appendix XXXII Urinary and Renal Function Tests Appendix XXXIII Bronchoalveolar Lavage Fluid Cell Populations Appendix XXXIV Cerebrospinal Fluid (CSF) Appendix XXXV Cerebrospinal Fluid Biochemical Analytes in Histologically Normal Cats Appendix XXXVI Characteristics of Body Cavity Fluids in Healthy Dogs and Cats Appendix XXXVII Cytologic Findings in Normal and Abnormal Canine Synovial Fluids Appendix XXXVIII Canine Semen Appendix XXXIX Canine Prostatic Fluid (Third Fraction) Appendix XL

Electrocardiography

section I Critical Care Nishi Dhupa

Chapter 1: Shock................................................................................................... 2 Chapter 2: Acute Pain Management..................................................................... 9 Chapter 3: Nutrition in Critical Care.................................................................. 18 Chapter 4: Antiplatelet and Anticoagulant Therapy.......................................... 24 Chapter 5: Cardiopulmonary Cerebral Resuscitation......................................... 28 Chapter 6: Traumatic Brain Injury...................................................................... 33 Chapter 7: Vascular Access Techniques............................................................... 38 Chapter 8: Pacing in the Critical Care Setting.................................................... 43 Chapter 9: Fluid Therapy..................................................................................... 48 Chapter 10: Acid-Base Disorders......................................................................... 54 Chapter 11: Colloid Fluid Therapy...................................................................... 61 Chapter 12: Acute Abdomen: Evaluation and Emergency Treatment................ 67 Chapter 13: Drainage Techniques for the Septic Abdomen................................ 72 Chapter 14: Gastric Dilation-Volvulus................................................................ 77 Chapter 15: Emergency Management of Open Fractures................................... 83 Chapter 16: Thoracic Trauma.............................................................................. 86 Chapter 17: Intravenous Anesthetic and Analgesic Techniques......................... 88 VOLUME XIII Content on EVOLVE: http://evolve.elsevier.com/Bonagura/Kirks/ Bacterial Translocation: Clinical Implications and Prevention Cats Are Not Dogs in Critical Care Collid Osmometry Epidural Analgesia

Lactate Measurement: Diagnostic, Therapeutic, and Prognostic Implications Microenteral Nutrition Point-of-Care Laboratory Testing in the Intensive Care Unit



C h apter  

1

Shock Annie Malouin, Philadelphia, Pennsylvania Deborah Silverstein, Philadelphia, Pennsylvania

S

hock is a state of severe hemodynamic and metabolic derangements. It is characterized by poor tissue perfusion from low or unevenly distributed blood flow that leads to a critical decrease in oxygen delivery (DO2) in relation to oxygen consumption (VO2) (Fig. 1-1) and/or inadequate cellular energy production. If the shock state is not promptly recognized and treated, neurohormonal compensatory mechanisms will lead to stimulation of the renin-angiotensin-aldosterone system, as well as baroreceptor and chemoreceptor-mediated release of catecholamines and subsequent production of counterregulatory hormones (glucagon, adrenocorticotropic hormone [ACTH], and cortisol). These changes will increase cardiovascular tone, activate a variety of biochemical mediators, and stimulate inflammatory responses that contribute to the shock syndrome. This progression can cause or exacerbate uneven microcirculatory flow, poor tissue perfusion, tissue hypoxia, altered cellular metabolism, cellular death, and vital organ dysfunction or failure. Box 1-1 lists the different types of shock, but this classification can be overly simplistic. Critically ill patients are subject to complex etiologic and pathophysiologic events and therefore may suffer from more than one type of shock simultaneously. The rationale for the functional classification of shock is the presumption that each underlying illness identified can be associated with a specific pathophysiologic process and rapid, appropriate therapy can be administered.

Clinical Presentation Dogs in compensatory shock demonstrate mild-to-moderate mental depression, increased heart rate, increased res­ piratory rate, peripheral vasoconstriction with cold extremities and pale mucous membranes, and a shortened capillary refill time with normal blood pressure. As compensatory mechanisms fail, they may develop severe mental depression, prolonged capillary refill time, increased heart rate, poor pulse quality, and decreased arterial blood pressure. Dogs with sepsis or a systemic inflammatory response syndrome (SIRS) can show clinical signs of hyperdynamic or hypodynamic shock. The initial hyperdynamic phase of sepsis is characterized by tachycardia, fever, bounding peripheral pulse quality, and hyperemic mucous membranes secondary to peripheral vasodilation. If septic shock or SIRS progresses unchecked, a decreased cardiac 

output and signs of hypoperfusion may ensue as a result of cytokine effects on the myocardium or myocardial ischemia. Clinical alterations may then include tachycardia, pale (and possibly icteric) mucous membranes with a prolonged capillary refill time, hypothermia, poor pulse quality and dull mentation. Hypodynamic septic shock is the decompensatory stage of sepsis and without intervention will result in organ damage and death. Finally, the gastrointestinal (GI) tract is the shock organ in dogs and often leads to ileus, diarrhea, or melena. In cats the hyperdynamic phase of shock is rarely recognized. Also, in contrast to dogs, changes in heart rate in cats with shock are unpredictable; they may exhibit tachycardia or bradycardia. In general, cats typically present with pale mucous membranes (and possibly icterus), weak pulses, cool extremities, hypothermia, and generalized weakness or collapse. In cats the lungs seem to be the organ most vulnerable to damage during shock or sepsis, and signs of respiratory dysfunction are common (Schutzer et al., 1993; Brady et al., 2000; Costello et al., 2004).

Management General Diagnostics For all patients in shock, basic diagnostic tests should be completed to assess the extent of organ injury and identify the etiology of the shock state. Venous or arterial blood gases, a complete blood cell count, blood chemistry panel, coagulation panel, blood typing, and urine analysis should be performed in all shock patients. Thoracic and abdominal radiographs, abdominal ultrasound, and echocardiography may be indicated once the patient is stabilized. Thoracic imaging can help distinguish cardiogenic forms of shock.

Monitoring Perfusion and Oxygen Delivery The magnitude of oxygen deficit is a key predictor in determining outcome in patients with shock. Therefore optimizing tissue perfusion and DO2 is the goal of effective therapy, and thorough monitoring is necessary to achieve this objective. An optimally perfused patient maintains the following characteristics: central venous pressure between 5 and 10 cm H2O (2 to 5 cm H2O in cats); urine production of at least 1 ml/kg/hour; a mean arterial pressure (MAP) between 70 and 120 mm Hg; normal body

Chapter  1  Shock

Oxygen consumption (VO 2)



DcO2

C

B

A

Oxygen delivery (DO2)

Fig. 1-1  The relationship between oxygen delivery and oxygen

consumption. In region B-C the oxygen consumption remains constant as oxygen delivery is increased. The oxygen supply is in excess of consumption, and VO2 is termed supply independent. During shock, as metabolic demand (VO2) increases or DO2 diminishes (C-B), Oxygen extraction ratio rises to maintain aerobic metabolism; thus consumption can remain independent of delivery. However, at point B, called critical DO2 (DcO2), the maximum OER is reached. This is believed to be 60% to 70%, and beyond this point any further increase in VO2 or decline in DO2 must lead to tissue hypoxia.

Box  1-1 Functional Classifications and Examples of Shock Hypovolemic: A Decrease in Circulating Blood Volume • Hemorrhage • Severe dehydration • Trauma Cardiogenic: A Decrease in Forward Flow From the Heart • Congestive heart failure • Cardiac arrhythmia • Cardiac tamponade • Drug overdose (e.g., anesthetics, β-blockers, calcium channel blockers) Distributive: A Loss of Systemic Vascular Resistance • Sepsis • Obstruction (heartworm disease, saddle thrombosis) • Anaphylaxis Metabolic: Deranged Cellular Metabolic Machinery • Hypoglycemia • Cyanide toxicity • Mitochondrial dysfunction • Cytopathic hypoxia of sepsis Hypoxemic: A Decrease in Oxygen Content in Arterial Blood • Anemia • Severe pulmonary disease • Carbon monoxide toxicity • Methemoglobinemia



temperature, heart rate, heart rhythm, and respiratory rate; and moist, pink mucous membranes with a capillary refill time of less than 2 seconds. Monitoring these parameters becomes the baseline of patient assessment. Additional monitoring elements that may prove beneficial include measuring blood lactate, indices of systemic oxygenation transport, and mixed venous oxygen saturation. Blood Lactate Levels Critically ill patients with inadequate tissue perfusion, DO2, or oxygen uptake, often have a hyperlactatemia and acidemia that reflect the severity of tissue hypoxia. Humans with lactic acidosis are at greater risk of developing multiple organ failure and demonstrate a higher mortality rate than patients without an elevated lactate concentration (Nguyen et al., 2004). High blood lactate levels may also help to prognosticate mortality in dogs (Boag and Hughes, 2005; de Papp E et al., 1999; Nel et al., 2004; Lagutchik et al., 1998). The normal lactate level in adult dogs and cats is reported to be less than 2.5 mmol/L; lactate concentrations greater than 7 mmol/L are considered severely elevated (Boag et al., 2005). However, normal neonatal and pediatric patients may have higher lactate concentrations (McMichael et al., 2005). In addition, sample collection and handling techniques can affect lactate concentration (Hughes et al., 1999). Serial lactate measurements can be taken during the resuscitation period to gauge response to treatment and evaluate the resuscitation end points; the trends in lactate concentrations are a better predictor of outcome than are single measurements. It is well documented that the ability of the body to correct an elevated lactate concentration is directly correlated to survival. Cardiac Output Monitoring and Indices of Oxygen Transport The most direct way to assess the progress of resuscitation in shock patients is to measure indices of systemic oxygen transport. Measurement and monitoring of these values requires right-sided cardiac catheterization, which is performed using a specialized pulmonary artery catheter (PAC, also termed Swan-Ganz catheter or balloondirected thermodilution catheter). The PAC allows access for the measurement of central venous and pulmonary arterial pressure, mixed venous blood gases (PvO2 and SvO2), pulmonary capillary wedge pressure (PCWP), and cardiac output. With these data additional information regarding the function of the circulatory and respiratory systems can be derived (i.e., stroke volume, end-diastolic volume numbers, systemic vascular resistance index, pulmonary vascular resistance index, arterial oxygen content, mixed venous oxygen content, DO2 index, VO2 index and the oxygen extraction ratio). The cardiac output is most commonly determined using thermodilution methods, although other techniques are available, including noninvasive Doppler-based methods. A PAC can provide the clinician with useful information to assess and monitor the cardiovascular and pulmonary function of shock patients. It may also help the clinician evaluate the response to therapeutic interventions and allow titration of fluid therapy, vasopressors,



Section  I  Critical Care

and inotropic agents. Cardiac output and systemic DO2 should be optimized by intravascular volume loading until the PCWP approaches 18 to 20 mm Hg. A higher PCWP (>18-20 mm Hg) promotes the formation of pulmonary edema; further impairing oxygenation and overall oxygen transport. In critically ill humans the cardiac index (CI), DO2, and VO2 have been found to be higher in survivors. Finally, the use of a PAC does not necessarily translate into reduced mortality in the critically ill shock patient; it is an invasive monitoring technique that is not without risk. Despite the fact that a tremendous amount of information can be obtained from the PAC, it is important to recognize that the accuracy of the measurements provided by the PAC rely on catheter placement, calibration of transducers, coexisting cardiac or pericardial disease, and interpretation of waveforms and measurements or calculations. PAC placement should be performed by experienced individuals, and interpretation of the data should be systematic. In humans the most common complications that occur during or after PAC insertion include arrhythmias, pulmonary injuries, thromboembolism, and sepsis. Mixed Venous Oxygen Saturation and Central Venous Oxygen Saturation Mixed venous oxygen saturation (SvO2) can be used clinically to assess changes in the global tissue oxygenation (oxygen supply-to-demand). If VO2 is constant, SvO2 is determined by cardiac output, hemoglobin concentration, and systemic arterial oxygen tension. The SvO2 is decreased if DO2 is decreased (low cardiac output, hypoxia, severe anemia) or if VO2 is increased (fever). SvO2 is increased in hyperdynamic stages of sepsis and cytotoxic tissue hypoxia (e.g., cyanide poisoning). A reduction in SvO2 may be an early sign that the patient’s clinical condition is deteriorating. Also, SvO2 may be a surrogate for measuring the CI during ­ resuscitative efforts.  Ideally SvO2 is measured in a blood sample from the pulmonary artery. However, in cases in which the insertion of a PAC is not possible or desirable, SvO2 can be determined in the central circulation, using a central venous catheter in the cranial vena cava. SvO2 is then termed central venous oxygen saturation (ScvO2). In critically ill patients with circulatory failure of any origin, ScvO2 values generally are higher than SvO2, but the two measurements closely parallel one another. Therefore the presence of a pathologically low ScvO2 likely indicates an even lower SvO2. The difference between the two values is usually about 5%; this is caused by the effect of blood flow redistribution and differences in oxygen consumption across the hepatosplanchnic, coronary, and cerebral circulations during shock states. Finally, a recent prospective randomized study comparing two algorithms for early goal-directed therapy in patients with severe sepsis and septic shock showed that maintenance of a continuously measured ScvO2 above 70% (in addition to maintaining central venous pressure above 8 to 12 mm Hg, MAP above 65 mm Hg, and urine output above 0.5 ml/kg/hour) resulted in a 15% absolute reduction in mortality compared to the same treatment without ScvO2 monitoring (see following paragraphs for further details) (Rivers et al., 2001).

Therapy If the animal is not breathing or displays signs of impending fatigue, immediate intubation and positivepressure ventilation should be instituted. If the animal is breathing spontaneously, oxygen is administered. This can involve flow-by methods (50 to 150 ml/kg/minute) such as simply holding the oxygen tubing up to the nose or administration of oxygen into a mask, hood, or bag. Nasal catheter(s) are effective methods of oxygen administration (using rates of 50 to 100 ml/kg/minute per catheter). Once the vital signs are obtained, vascular access is established, and fluid administration is initiated if indicated. It is of utmost importance that preliminary diagnostics and appropriate treatment are rapidly initiated to maximize DO2 to the tissues and prevent irreversible shock.

Fluid Therapy Vascular Access The first and most important therapeutic goal for noncardiogenic shock is to restore the effective circulatory volume. Appropriate vascular access is essential for rapid administration of large volumes of fluid (see Chapter 7 for further details). Poiseuille’s law of flow states that resistance to flow through a catheter is directly proportional to the length of the catheter and inversely related to the fourth power of the radius. Thus large-bore, short intravenous catheters should be placed for resuscitation. For cats and small dogs 18- or 20-gauge catheters should be used; for larger dogs multiple venous catheters (14- to 18gauge) should be placed. Faster intravenous fluid administration can be further facilitated by applying pressure around the fluid bag with a commercial pressure device or a blood pressure cuff. Crystalloids Isotonic crystalloids remain the cornerstone of treatment for noncardiogenic shock. Examples include 0.9% sodium chloride, lactated Ringer’s solution, Normosol-R, and Plasmalyte-148. A shock dose of isotonic crystalloid solution is approximately one blood volume (i.e., 90 ml/ kg in the dog and 50 ml/kg in the cat). The fluid administered rapidly distributes into the extracellular fluid compartment so that only ≈25% of the delivered volume remains in the intravascular space by 30 minutes after infusion (Silverstein et al., 2005). Although theoretically this increase in interstitial fluid volume might predispose to interstitial edema and deranged oxygen transfer to the cells, this has not been proven in human clinical trials. However, it is important that excessive fluid volumes are not administered to avoid volume overload. It is generally recommended that one third to one half of the shock dose be administered as quickly as possible, followed by additional boluses as indicated by clinical parameters and repeated physical examination. In patients that are bleeding it may even be advantageous to perform “hypotensive resuscitation” (to a MAP of ≈60 mm Hg) until the hemorrhage is controlled since aggressive fluid therapy in this setting can worsen bleeding and outcome. For animals with coexisting head trauma, the



Chapter  1  Shock



isotonic crystalloid of choice is 0.9% NaCl since it contains the highest concentration of sodium and is least likely to contribute to cerebral edema.

shock. A 1:2.5 ratio of 23.4% NaCl with dextran 70 or hetastarch makes an ≈7.5% saline mixture (44 ml of 23.4% NaCl in 106 ml of dextran 70 or hydroxyethyl starch).

Hypertonic Solutions Hypertonic (7% to 7.5%) sodium chloride administration causes a transient osmotic shift of water from the extravascular to the intravascular compartment. It is administered in small volumes (5 ml/kg) intravenously (IV) over 5 to 10 minutes. In addition to the fluid compartment shift caused by hypertonic saline, there is evidence that it may also be beneficial to reduce endothelial swelling, increase cardiac contractility, cause mild peripheral vasodilation, and decrease intracranial pressure. Because of the osmotic diuresis and rapid redistribution of the sodium cations that ensue following the administration of hypertonic saline, the intravascular volume expansion is transient (20,000 daltons) that do not readily sieve across the vascular membrane. The colloidal particles in the most commonly used synthetic colloids (dextran 70 and hydroxyethyl starch) are suspended in 0.9% NaCl. They are hyperoncotic to the normal animal and therefore pull fluid into the vascular space. They cause an increase in blood volume that is greater than that of the infused volume and help to retain this fluid in the intravascular space in animals with normal capillary permeability. Dextran 70 is a 6% colloidal solution with particles that range from 15,000 to 3,400,000 daltons, a number average molecular weight of 41,000, and a colloid osmotic pressure of 60 mm Hg. Hetastarch is also a 6% solution with particles ranging from 10,000 to 1,000,000 daltons in molecular weight, a number average molecular weight of 69,000 daltons, and a colloid osmotic pressure of 34 mm Hg. The recommended dose of synthetic colloids for the treatment of shock is up to 20 ml/kg in the dog and up to 10 ml/kg in the cat (note that rapid administration of hydroxyethyl starch in the cat has been reported to cause vomiting). Excessive volumes can lead to volume overload, coagulopathies, and hemodilution. These fluids are appropriately used for shock therapy in acutely hypoproteinemic animals (total protein less than 3.5 g/dl) with a decreased colloid osmotic pressure. They can also be used with isotonic or hypertonic crystalloids to maintain adequate plasma volume expansion with lower interstitial fluid volume expansion and to expand the intravascular space with smaller volumes over a shorter time period. Despite multiple clinical studies in humans, there is no definitive documentation that the use of colloids is superior to the use of crystalloids for resuscitation, and the price of colloids is significantly greater than that of crystalloids (for further details, see Chapter 11). Hypertonic Saline Plus Synthetic Colloid Solutions To prolong the effect of the resuscitation fluids, a hypertonic saline/synthetic colloid (dextran 70 or hydroxyethyl starch) mixture can be administered for the treatment of

Human Serum Albumin Solution Animals with severe hypoalbuminemia may benefit from treatment with 25% human albumin. Albumin is crucial in the transport of drugs, hormones, chemicals, toxins, and enzymes. Preliminary studies in dogs show that human albumin administration in dogs increases circulating albumin concentrations, total solids, and colloid osmotic pressure, although the effect on mortality remains unknown. Current and future studies will provide more information regarding the use of this product. Potential risks are similar to those for any blood transfusion (i.e., fever, vomiting, increased respiratory effort) in addition to the potential for increasing clotting times.



Section  I  Critical Care

Recent reports of albumin-induced anaphylaxis in ­normal dogs require further investigation (Mathews and Barry, 2005).

Vasopressors and Positive Inotropes Shock patients that remain hypotensive despite intravascular volume resuscitation often require vasopressor and/or inotrope therapy. Since both cardiac output and systemic vascular resistance affect DO2 to the tissues, therapy for hypotensive patients includes maximizing cardiac function with fluid therapy and inotropic drugs and/or modifying vascular tone with vasopressor agents. This is particularly important in cardiogenic shock (see Chapter 171). Commonly used vasopressors include catecholamines (epinephrine, norepinephrine, and dopamine) and the sympathomimetic drug phenylephrine. In addition, vasopressin, corticosteroids, and glucagon have been used as adjunctive pressor agents. Different sympathomimetics cause various changes in the cardiovascular system, depending on the specific receptor stimulation caused by the drug. Conventionally adrenergic receptor location and function involve the α-1 and β-2 receptors located on the vascular smooth muscle cells that lead to vasoconstriction and vasodilation, respectively, whereas β-1 receptors in the myocardium primarily modulate inotropic and chronotropic activity. In addition, there are dopaminergic-1 receptors in the renal, coronary, and mesenteric microvasculature that mediate vasodilation and dopaminergic-2 receptors in the synaptic nerve terminals that inhibit the release of norepinephrine. Dopamine has various potential actions on adrenergic and dopaminergic receptors. Primarily dopaminergic effects are seen at low intravenous dosages (1 to 5 mcg/ kg/minute); mainly β-adrenergic effects are seen at moderate dosages (5 to 10 mcg/kg/minute); mixed α- and β-adrenergic effects are present at high dosages (10 to 15 mcg/kg/minute); and primarily α-adrenergic effects are seen at very high dosages (15 to 20 mcg/kg/minute). The actual dose-response relationship is unpredictable in a given patient because it depends on individual variability in enzymatic dopamine inactivation, receptor downregulation, and the degree of autonomic derangement. Dopamine can be used as a single-agent therapy to provide both inotropic and pressor support in animals with vasodilation and decreased cardiac contractility. In comparison to other pressor drugs, dopamine is a less potent inotrope than epinephrine (or dobutamine) and less vasoconstricting than norepinephrine. The cardiovascular effects of dopamine may dissipate after several days of therapy, perhaps because of receptor down-regulation and/or induction of increased postsynaptic norepinephrine release. Despite the beneficial effects of dopamine on cardiac output and blood pressure, it may have deleterious effects on renal, mesenteric, and skeletal blood flow. Norepinephrine (NE) has mixed α- and β-adrenergic receptor agonist effects with preferential α- receptor activity. Therefore the effects on heart rate and contractility are mild, and NE is commonly used as a pressor agent in animals with normal or increased cardiac output states. Canine septic shock models have demonstrated that the

effects of NE on cardiac function are diminished compared to those of nonseptic controls. In septic patients with cardiac insufficiency and vasodilation, it may be desirable to use NE in conjunction with dobutamine (a potent β-agonist) to prevent the deleterious effects of increasing afterload in the face of a diseased heart. Renal blood flow may improve in animals with septic shock so long as arterial blood pressure is normalized. Conversely, NE administration to dogs with hypovolemic shock induces deleterious renal vasoconstriction. NE was also shown to improve urine output and creatinine clearance when added to dopamine or dobutamine in human patients with septic shock. Enhanced splanchnic DO2 and increases in gastric mucosal pH are evident in humans who receive NE therapy for the treatment of hypotensive septic shock. The vasopressor dosage of NE in humans (and extrapolated to dogs) is 0.05 to 3.3 mcg/kg/minute IV. Epinephrine (Epi) is a potent pressor with mixed α- and β-agonist activity. Although Epi is thought to have more potent β-agonist effects than NE, individual response is quite variable in patients with systemic inflammatory diseases and hypotension. Epi may significantly impair splanchnic blood flow compared to norepinephrine and dobutamine (in combination). This is most likely because of the strong α-adrenergic activity of Epi with subsequent vasoconstriction in regional vascular beds, although Epi also activates vasodilatory β-receptors. The vasopressor dosage of intravenous Epi is 0.01 to 0.1 mcg/kg/minute and for primarily β-agonist effects 0.005 to 0.02 mcg/kg/ minute. Epi is rarely used as a sole first-line vasopressor agent because of its potential side effects, but it may be necessary in critically ill animals. Epi also inhibits mast cell and basophil degranulation and therefore is the drug of choice in patients suffering from anaphylactic shock. It is also commonly used for the treatment of cardiac arrest. Phenylephrine is a pure α-agonist drug that causes profound vasoconstriction. It has been shown to cause an increase in cardiac output and blood pressure, presumably as a result of increased venous return to the heart and activation of α-1 receptors in the myocardium. Typically phenylephrine is used in patients that are unresponsive to other sympathomimetics, although it can be used as a sole first-line agent in vasodilated, hypotensive animals. Since phenylephrine has no β-agonist activity, it is the least arrhythmogenic of the sympathomimetic pressor drugs and therefore is desirable in animals that develop tachyarrhythmias in response to other pressor agents. The intravenous dosage range is 0.5 to 3 mcg/kg/minute. Dobutamine is a β-agonist with weaker, dosedependent α-effects. It increases cardiac output, DO2, and VO2 without causing vasoconstriction at lower doses. Therefore it is useful in animals with shock caused by cardiac insufficiency. Dobutamine may worsen or precipitate tachyarrhythmias and may precipitate seizure activity in cats. The intravenous dosage range is 1 to 5 mcg/kg/minute in cats and 2.5 to 20 mcg/kg/minute in dogs. Vasopressin is a nonadrenergic vasopressor agent. It has both direct and indirect effects on the vascular smooth muscle via the V1 receptors and induces

Chapter  1  Shock

­ asoconstriction in most vascular beds. In vitro vasopresv sin is a more potent vasoconstrictor than phenylephrine or NE. At low doses this drug causes vasodilation in renal, pulmonary, ­mesenteric, and cerebral vasculature in an attempt to maintain perfusion to these vital organs. Low flow states secondary to hypovolemia or septic shock are associated with a biphasic response in endogenous serum vasopressin levels. There is an early increase in the release of vasopressin from the neurohypophysis in response to hypoxia, hypotension, and/or acidosis, which leads to high levels of serum vasopressin. This plays a role in the stabilization of arterial pressure and organ perfusion in the initial stages of shock. There appears to be a subsequent decrease in circulating vasopressin levels, most likely a result of a depletion of hypothalamic stores. Therefore the use of vasopressin in animals in the later stages of shock, especially those that exhibit vasodilation and are refractory to catecholamine therapy, may be beneficial. The drug also enhances sensitivity to catecholamines and therefore may allow the dose of concurrent catecholamine therapy to be lowered. Experimental studies in dogs have demonstrated an increase in blood pressure and cardiac output with minimal side effects. A clinical case series using vasopressin at 0.5 to 4 mU/ kg/minute found an increase in blood pressure following vasopressin therapy as well. This drug will require further investigation but may be considered in animals with catecholamine-resistant vasodilatory shock. Glucagon typically is secreted from the pancreas and is classified as a counterregulatory hormone. It activates adenylate cyclase independent of β-adrenergic receptor stimulation. Exogenously administered glucagon causes a positive inotropic effect that leads to an increase in cardiac output and blood pressure. This drug may be useful in critically ill patients that are unresponsive to β-agonist drugs or those receiving sympathomimetic therapy that is complicated by β-blocker agents. Further research is needed.

Antimicrobials Early antibiotic therapy is important in shock patients with proven or suspected sepsis. If possible, properly collected cultures of blood, urine, respiratory secretions (collected by endotracheal wash, transtracheal wash, or bronchoscopy) and other available body fluids (i.e., pleural, peritoneal, or cerebrospinal fluid) should be sampled carefully before antimicrobial therapy is begun. Broadspectrum antibiotic therapy should be initiated pending culture and sensitivity results. Empiric antibiotic choices should be effective against gram-positive and gramnegative organisms and anaerobes. Initial combinations might include ampicillin (22 mg/kg IV q6-8h) and enrofloxacin (15 mg/kg IV q24h in dogs, 5 mg/kg IV q24h in cats); ampicillin and amikacin (15 mg/kg IV q24h); cefazolin (22 mg/kg IV q8h) and amikacin, ampicillin, and ceftazidime (22 mg/kg IV q8h); or clindamycin (10 mg/kg IV q8-12h) and enrofloxacin. Single agents such as ticarcillin/clavulanic acid (50 mg/kg IV q6h), cefoxitin (15 to 30 mg/kg IV q4-6h), or imipenem (5-10 mg/kg IV q6-8h, if bacterial resistance is suspected) could be used initially as well.



Gastrointestinal Protection Stress-related mucosal disease (SRMD) and subsequent upper GI bleeding are frequently seen in critically ill humans and may also occur in dogs and cats. Clinical signs of hematemesis, hematochezia, or melena should alert the clinician to potentially serious GI hemorrhage. Hypoperfusion of the upper GI mucosa during shock, excessive gastric acid secretion, and impaired mucosal defense mechanisms (mucus secretion, production of growth factors) contribute to the development of SRMD. Furthermore, in humans factors thought to increase the risk of stress-related GI hemorrhage include prolonged mechanical ventilation, extensive burns, hepatic failure, renal failure, coagulopathy, head injuries, multiple trauma, high-dose corticosteroids, nonsteroidal antiinflammatory use, and absence of enteral nutrition. In veterinary patients the incidence of SRMD and clinically significant bleeding is unknown; therefore no guidelines exist for their management. The initial strategy in critically ill dogs and cats should be to ensure adequate GI perfusion and use early enteral nutrition. High-risk patients should receive pharmacologic prophylaxis for stress-related GI hemorrhage. Based on the currently available evidence in human medicine, it appears that proton pump inhibitors (PPIs) are superior to histamine-2 receptor antagonists (H2RAs), which are superior to sucralfate in the prevention of SRMD in adult critical-care patients. Drugs available include omeprazole (PPI) 0.7 to 1 mg/kg PO q24h, pantoprazole (PPI) 0.7 to 1 mg/kg IV q24h, famotidine (H2RA) 0.5 to 1 mg/kg IV q12-24h PO, ranitidine (H2RA) 0.5 to 4 mg/kg IV q8-12h, and sucralfate (protectant) 0.25 1 g/25 kg PO q6-8h. Recent evidence suggests that ranitidine does not decrease acid production in dogs at clinically recommended doses (Bersenas et al., 2005; Cook et al., 1999).

Nutrition Following initial stabilization of the shock patient, nutritional status should be addressed (see Chapter 3). Ade­quate nutrition is critical in patients with secondary hypermetabolic states such as sepsis. The enteral route (orally or via nasoesophageal, esophagostomy, gastrostomy, or jejunostomy tube) is preferable if the animal is normotensive, not vomiting, and alert. Parenteral nutrition should be administered if the enteral route is not feasible or contraindicated. If the blood glucose falls below 60 g/dl, 0.5 ml/kg of 50% dextrose should be diluted 1:1 with sterile water and administered IV over 1 to 2 minutes. The fluids should also be supplemented with dextrose as needed (2.5% to 7.5%). Hyperglycemia should be avoided since it has been associated with an increased likelihood of infection and a poorer prognosis.

Novel Therapeutic Strategies Early Goal-Directed Therapy For many years it has been recognized that critically ill patients in shock benefit from rapid normalization of abnormal physiologic functions. Many therapeutic strategies have been studied, including reestablishing normal



Section  I  Critical Care

or even supranormal hemodynamics values to improve the outcome of patients in shock. Although the use of supranormal resuscitation has not proven beneficial, the use of early goal-directed therapy has shown early promise (Kern and Shoemaker, 2002). Early goal-directed therapy is performed using a series of predefined resuscitation end points to help clinicians resuscitate shock patients as soon as the syndrome is recognized. The aim of these specific end points is to adjust cardiac preload, contractility, and afterload to balance systemic DO2 with demand. Recently the effect of early goal-directed therapy was evaluated in a prospective, randomized clinical trial that included humans who presented to an emergency room with severe sepsis, septic shock, or sepsis syndrome (Rivers et al., 2001). During the first 6 hours of resuscitation from sepsis-induced hypoperfusion, patients treated with early goal-directed therapy received, in a sequential fashion, fluid resuscitation, vasopressors or dilator agents, red-cell transfusions, and inotropic medications to achieve target levels of central venous pressure (8 to 12 mm Hg), MAP (65 to 90 mm Hg), urine output (as least 0.5 ml/kg of body weight), and ScvO2 (at least 70%). The other group of patients was treated following a standard therapy at their clinician’s discretion. Ultimately patients resuscitated following the early goal-directed therapy plan had higher survival rates. In dogs and cats initiating a similar goal-directed therapy strategy immediately after recognition of a shock syndrome might be beneficial. The use of ScvO2 monitoring requires further research in veterinary patients. Relative Adrenal Insufficiency and Use of Steroids Adrenal insufficiency of critical illness is a well-recognized clinical entity in humans, especially those suffering from sepsis (Cooper and Stewart, 2003). These patients have an increased morbidity and mortality, and the use of physiologic doses of steroids has been shown to improve outcome. Adrenal insufficiency may be secondary to both a decrease in glucocorticoid synthesis (i.e., adrenal insufficiency) and peripheral resistance to glucocorticoids. The diagnosis of the dysfunction relies on assessment of plasma cortisol before and after exogenous corticotropin administration (ACTH stimulation test). A relative adrenal insufficiency may lead to refractory hypotension in shock patients or those with critical illness since steroids normally suppress endogenous vasodilators such as the kallikrein-kinin system, prostacyclin, and nitric oxide. Glucocorticoids also modify the renin-angiotensin system and up-regulate angiotensin II receptors in the vasculature. The use of physiologic doses of steroids in people with refractory hypotension has been well studied (Annane et al., 2004). Critically ill, hypotensive animals may also benefit from physiologic doses of corticosteroids, but further research is required to confirm this. There is controversy regarding the definition of an “adequate” response, the dose of ACTH that should be administered, and the constituents of “replacement” therapy.

In specific situations critically ill patients might benefit from glucocorticoid supplementation. The use of etomidate, which blocks the synthesis of cortisol by reversible inhibition of 11-β-hydroxylase, has an inhibitory effect on adrenal function in critically ill patients and has been associated with an increase in intensive care unit mortality. Patients receiving treatment with corticosteroids for chronic autoimmune or inflammatory diseases and those receiving replacement therapy for hypoadrenocorticism should receive at least physiologic doses of prednisone or dexamethasone during severe illness.

References and Suggested Reading Annane D et al: Corticosteroids for treating severe sepsis and septic shock, Cochrane Database Syst Rev 1:CD002243, 2004. Bersenas AM et al: Effects of ranitidine, famotidine, pantoprazole, and omeprazole on intragastric pH in dogs, Am J Vet Res 66(3):425, 2005. Boag A, Hughes D: Assessment and treatment of perfusion abnormalities in the emergency patient, Vet Clin North Am Small Anim Pract 35(2):319, 2005. Brady CA et al: Severe sepsis in cats: 29 cases (1986-1998), J Am Vet Med Assoc 217(4):531, 2000. Cook D et al: Risk factors for clinically important upper gastrointestinal bleeding in patients requiring mechanical ventilation, Crit Care Med 27(12):2812, 1999. Cooper MS, Stewart PM: Corticosteroids insufficiency in acutely ill patients, N Engl J Med 348:727, 2003. Costello MF et al: Underlying cause, pathophysiologic abnormalities, and response to treatment in cats with septic peritonitis: 51 cases (1990-2001), J Am Vet Med Assoc 225(6):897, 2004. dePapp E et al: Plasma lactate concentration as a predictor of gastric necrosis and survival among dogs with gastric-volvulus: 102 cases (1995-1998), J Am Vet Med Assoc 215(1):49, 1999. Hughes D et al: Effect of sampling site, repeated sampling, pH and Pco2, on plasma lactate concentration in healthy dogs, Am J Vet Res 60(4):521, 1999. Kern JW, Shoemaker WC: Meta-analysis of hemodynamic optimization in high-risk patients, Crit Care Med 30(8):1686, 2002. Lagutchik MS et al: Increased lactate concentrations in ill and injured dogs, J Vet Emerg Crit Care 8(2):117, 1998. Mathews KA, Barry M: The use of 25% human serum albumin: outcome and efficacy in raising serum albumin and systemic blood pressure in critically ill dogs and cats, J Vet Emerg Crit Care 15(2):110, 2005. McMichael MA et al: Serial plasma lactate concentration in 68 puppies aged 4 to 80 days, J Vet Emerg Crit Care 15(1):17, 2005. Nel M et al: Prognostic value of blood lactate, blood glucose and hematocrit in canine babesiosis, J Vet Intern Med 18(4):471, 2004. Nguyen HB et al: Early lactate clearance is associated with improved outcome in severe sepsis and septic shock, Crit Care Med 32 (8):1637, 2004. Rivers E et al: Early goal directed therapy in the treatment of severe sepsis and septic shock, N Engl J Med 345:1368, 2001. Schutzer KM et al: Lung protein leakage in feline septic shock, Am Rev Respir Dis 147:1380, 1993. Silverstein DC et al: Assessment of changes in blood volume in response to resuscitative fluid administration in dog, J Vet Emerg Crit Care 15(3):185, 2005.

cH A P T E R  

2

Acute Pain Management Andrea L. Looney, Ithaca, New York

A

cute pain has many causes in the small animal population, from vehicular injury, myocardial damage, and musculoskeletal pain, through crush or fall injuries, pancreatitis, and gastric distention, to quill migration, disk injury, and surgical pain. Regardless of injury type, all patients share at least one common pathology—pain. Yet, despite this universality, there appears to be no clear definition across patients. However, we do know that pain induces many physiologic changes that can be acutely detrimental to patients. Among these are increased sympathetic tone, decreased or shunted gastrointestinal (GI) or urinary blood flow, increased blood viscosity, prolonged clotting time, and platelet aggregation. Long-term effects of uncontrolled pain include thromboembolism, ventilation perfusion mismatch, hypoxemia, hypercapnia, increased myocardial work and oxygen consumption, immuno­suppression, decreased wound healing, and increased incidence of postsurgical complications. Because pain had surpassed the definition of “detriment” and was becoming recognized as an actual disease, the Joint Commission on Accreditation of Healthcare Organizations (JCAHO) announced standards for the regular assessment and management of pain in humans in 1999. The American Animal Hospital Association (AAHA) followed suit in 2003, releasing its Pain Management Standards, established to define pain in both preventable and treatable terms for all small animal patients. The American Pain Society has declared pain the “fifth vital sign.” Accordingly, pain should now be assessed both subjectively and objectively in all veterinary inpatients and outpatients along with other vital parameters. This chapter describes assessment, prevention, and treatment of acute pain in these types of critical patients, cognizant of the emergent nature of many diseases, but striving toward appropriate analgesic management.

Pain Scoring in Critically Ill Animals The importance of assessing pain is magnified when caring for critically ill, intensive care, acutely traumatized, or surgical patients. Recent literature in emergency medicine suggests that intubated patients near or after code receive inadequate analgesia, likely because of initial misconceptions regarding autonomic signs. In one study intubated patients with hypertension received analgesia; those with hypotension did not. Higher mortality rates were seen in the latter group. Retrospective analysis demonstrated both groups to have shown subtle yet unequivocal behavioral signs of pain. Slower regular administration of analgesics (such as continuous-rate infusions [CRIs]), choosing analgesics with less effect on cardiac output (opioids, nonsteroidals), and using simple nonpharmacologic methods

of analgesia (e.g., local blockade, ice) would have been appropriate for these patients despite their hypotension. Animals with systemic inflammatory response syndrome demonstrate pain-induced dysfunction of neurons, vasculature, and many major organs; however, it is particularly difficult even for well-trained nurses, technicians, and clinicians to evaluate these patients regarding pain. Although acute pain is associated with objective physiologic signs caused by autonomic nervous system activity, the critical or emergent patient may already be experiencing signs such as tachycardia, tachypnea, hypertension, and changes in blood glucose secondary to the surgical, traumatic, or acute-on-chronic conditions. Critical patients also have iatrogenically induced pain from recumbency, venipuncture, bandages or wraps, turning, wound care, catheterization, and suctioning. A recent study undertaken by the American Association of Critical Care Nurses identified positional turning alone as one of the most distressful and painful procedures for recent surgical and traumatized adult humans. Pain in these patients is also amplified as a result of stress, altered sleep, urination and defecation cycles, dietary changes, fear, anxiety, and polypharmacy interactions. Also unfortunate is the fact that pain may be unappreciated in the heavily sedated, paralyzed, or ventilated patient. Pain scoring is the repetitive process whereby pain status is assessed regularly. More important than choosing one scoring system over another are a few simple facts: (1) serial assessment using both behavioral and physiologic parameters should be used; (2) pain should be included as a cause of changes in physiologic parameters such as hypercapnia, tachycardia, or changes in blood sugar; (3) individual behaviors suggestive of pain should override any “scoring”; and (4) the gold standard for determining if pain is the cause of a physiologic or behavioral change is administration of an analgesic drug or technique and observation of its effect. Although recent veterinary literature has stressed attention to both physiologic and behavioral characteristics of pain, it can be challenging to differentiate among the possible etiologies within critical patient populations. As such, behavioral “scoring” often takes precedence; appreciation of both overt and subtle changes in demeanor, responsiveness, and interaction qualities is needed. In noncomatose patients, if objective characteristics of pain are not convincing, the patient should be examined for overt behavioral signs of pain. These include panting, shaking, increased respiratory effort, inability to position or move appropriately, pain on palpation near or distant from the wounds, licking, chewing, inappetence, crying, barking, and anxiety. The University of Melbourne Pain Scale and the Glasgow Composite Measures Pain Scale short form offer two well-established pain-scoring systems for 

10

Section  I  Critical Care

Box  2-1

Box  2-2

Simple Pain Scoring System for Noncomatose Patients

Pain Scoring System for Comatose, Heavily Sedated, Anesthetized, Intubated, Paralyzed, or Mechanically Ventilated Patients

Technicians, nursing staff and clinicians ask these seven questions regularly (q2-6h in critical, emergent, or trauma patients). Answers to the questions guide assignment of a “score” based on a scale of 0 to 5, denoted on the line below. Final scoring is subjective but should be relative to the patient’s previous score. Any obvious behavioral or physiologic sign indicative of pain automatically places the score at more than 3. 1. Is the patient’s heart rate and respiratory rate comparable to its preinsult or species normal values? 2. Is the patient willing to get up, walk unassisted, and move without discomfort? 3. Is the patient’s anxiousness, nervousness, aggravation, restlessness controlled? 4. Is the patient vocally quiet at rest and during interaction? 5. Is the patient appetent or interested in eating? 6. Can you palpate on or near the surgical site without the patient reacting? 7. Are your interactions with the patient pleasing to you and to him or her? More “yes” answers to the above questions indicate lower pain scores (better-controlled pain). More “no” answers to the above questions indicate higher pain scores (animals need additional analgesia). * 0 1 Comfortable

2

3

* 4 5 Very painful

use in noncomatose patients. My own simple pain-scoring system for noncomatose patients is included in Box 2-1. In addition, within this population, some experts believe anxiety and pain should be scored and treated independently. However, in the comatose patient pain is still present but with less overtly apparent expressions. Recent critical-care nursing literature shows that, no matter the level of consciousness, comatose and near-comatose adult patients react to a noxious stimulus by expressing subtle behavioral signs associated with pain. In veterinary patients I recommend close attention to subtle subjective assessment (presence or absence of squinting, grimacing, minor muscle twitching, papillary dilation, sphincter tone changes, body temperature changes, teeth grinding or chattering, ear pinning, photophobia), especially during nursing care or wound palpation, as a means of pain scoring. My painscoring system designed for comatose, mentally obtunded, sedated, or ventilated patients is summarized in Box 2-2.

Therapy Systemically administered opioids, α-2 adrenergic agonists, local anesthetics, and nonsteroidal antiinflammatory drugs (NSAIDs) are most widely used for acute pain therapy. Recently anticonvulsants, channel blocking agents, reuptake inhibitors, calcitonin, magnesium, β-blockade agents, bisphosphonates, and ketamine (classically labeled adjunctive agents) have been used to treat acute pain. Using a combination of drugs and techniques with different

Technicians, nursing staff, and clinicians ask these questions regularly (q2-6h). Answers to the questions guide assignment of a “score” based on a scale of 0 to 5, denoted on the line below. Final scoring is subjective but should be relative to the patient’s previous score. Any obvious behavioral or physiologic sign indicative of pain automatically places the score at more than 3.   1. Is the patient’s heart rate and respiratory rate comparable to its preinsult or species normal values?   2. Has pain been ruled out as a differential for vital parameter changes? (Test dose of fentanyl 3 to 5 mcg/kg and midazolam 0.1 to 0.3 mg/kg can be used to determine if pain is cause of parameter changes.)   3. Is the patient quiet at rest? (Listen for subtle moaning, crying, whining, or grunting. Mechanical ventilation may need to be silenced momentarily to perceive subtle vocalizations, especially in cats.)   4. Subtle muscle twitches or contractions; tremors; or fasciculations, including grimacing, squinting, whisker movement, lip, or muzzle changes; are not seen during interaction or observation. Is this true?   5. Overt stiffening of axial or appendicular muscles, splinting, opisthotonos or ventriflexion - is not seen during interaction. Is this true?   6. Palpation at or near the insult, injury, or surgical site is not painful. Is this true?   7. Defecation or urination is not seen during interaction. Is this true?   8. Urinary or anal sphincter tone does not change with interaction near or distant to the insult or injury site. Is this true?   9. There is an absence of teeth chattering, grinding, or temporomandibular and oropharyngeal activity during interaction or observation. Is this true? 10. There is no lacrimation or salivation seen with interaction or palpation of surgical/injury site. Is this true? 11. Increased or abdominal effort on inspiration is not observed, and respirations appear easy and uninhibited, not impeding mechanical ventilation if present. Is this true? More “yes” answers to the above questions indicate lower pain scores (better-controlled pain). More “no” answers to the above questions indicate higher pain scores (animals need additional analgesia). * 0 1 Comfortable

2

3

4

* 5 Very painful

pain control mechanisms (known as multimodal therapy) improves analgesia and allows for a lower dosage of each single drug (supraadditive or synergistic effect), minimizing adverse drug effects of individual drugs. Ideally both nonpharmacologic and pharmacologic analgesia therapies should be directed at any or all of the four major steps in the nociceptive pathway: transduction at the periphery, transmission along neuronal axons to the dorsal horn of the spinal cord (peripheral nerves) or brainstem (cranial nerves), modulation at the dorsal horn of the spinal cord, and perception at the cerebrum. 

Chapter  2  Acute Pain Management 11



Major Pharmacologic Agents Opioid Analgesics Opioids that interact with the mu receptor (fentanyl, morphine, oxymorphone, and hydromorphone) are noted for their ability to produce profound analgesia with mild if any sedation and little cardiovascular change. These are considered major analgesics and constitute the first line of pain control for critical, emergent, and acutely ill patients. Fentanyl, hydromorphone, and oxymorphone are my choices for acute pain management. Slow (over 2- to 5-minute) boluses constitute firstline analgesia, especially for the critical or acutely injured patient; CRIs of morphine, remifentanil, and fentanyl or, alternatively, intermittent injections of hydromorphone or oxymorphone allow continued analgesia in the same patient. Remifentanil is a potent analgesic requiring close attention to ventilatory status, but it is extremely useful because of its short half-life and metabolism via plasma esterases. Butorphanol, a mixed agonist-antagonist opioid, and buprenorphine, a partial agonist opioid, are not candidates for acute pain therapy because of their shortlived analgesic effect, profound sedative effect (masking pain), potent receptor adhesion, and ability to even potentiate (versus treat) pain. A common “cocktail” used to treat patients in acute pain is the combination of an opioid (hydromorphone or oxymorphone 0.1 mg/kg, or fentanyl 3 to 5 mcg/kg) with a benzodiazepine (midazolam or diazepam 0.3 mg/ kg) intravenously. Ketamine can also be added to these agents to provide analgesia along with immobilization. In most patients (except the animal with hypertension, hyperthyroidism, or overt cardiac failure), doses of 1 to 2 mg/kg of ketamine are usually well tolerated as an addition to the above cocktail. Transdermal opioids such as the fentanyl patch can be used as part of multimodal management. However, systemic uptake is very unreliable, especially in patients with circulatory and heat discrepancies. Furthermore, these agents are not capable of producing the immediate and profound analgesia necessary in traumatic, acute, or emergent situations. Transdermal systems are best used out of the emergent period or as adjunct methods of analgesia combined with more potent narcotics (intravenous [IV] opioids) and other agents initially. Fentanyl patches are best used in chronic, low-level pain states. Of the major side effects seen with opioids, foremost is dose-related respiratory depression reflecting diminished response to carbon dioxide levels. Nausea, vomiting, and dysphoria are commonly observed in animals that are not in pain. The vast majority of injured patients either do not show or can tolerate these side effects. Outside of mild bradycardia, narcotics produce few if any clinically significant cardiovascular effects in dogs and cats. Bradycardia alone should not be contraindications to opioid use, especially in acute, emergent, or critical patients. Because opioids increase intracranial and intraocular pressure, they should be used more cautiously in patients with severe cranial trauma and/or ocular lesions. However, even in these patients opioids can be used with slow initial IV boluses, titratable CRI or intermittent low-dose intramuscular (IM) or partial IV/IM dosing. These approaches minimize vomiting and potent respiratory depression in ocular and head trauma patients. Most opioids depress

the cough reflex via a central mechanism; this may be an advantage in intubated patients but may occasionally predispose to aspiration pneumonia. Certain of the opioids are capable of causing intense histamine release (morphine/meperidine), which precludes them from being administered intravenously, at least in high dosages. Hydromorphone may cause panting but, more important, seems to cause consistent vomiting in small animals and frequent, sometimes dangerous, hyperthermia in cats. Repetitive use of opioids as solo analgesics often results in two complications: urinary retention and GI ileus (with inappetence, nausea, and constipation). Treatment of these complications involves multimodal therapy (using another form of analgesic concomitantly with the opioid), using a more titratable opioid (fentanyl or remifentanil), using antiemetic and prokinetic drugs, and instituting minor physical therapy (massage, passive range of motion [PROM], walking) if the patient’s injury affords. Although analgesics are given intravenously whenever possible to ensure distribution of the drug and to avoid the need for painful IM injections, use of split IV and IM/ subcutaneous dosing at regular intervals (q6-8h) can reduce GI and urinary side effects, dysphoria, and agitation/panting, especially in feline patients. A key characteristic of opioids that makes them desirable for use in emergency and critica-care situations is their reversibility. All reversal agents such as naloxone and naltrexone should be administered slowly (over 10 minutes) if given intravenously, in diluted form, and to effect. Many of the opiate reversal agents are stimulatory to the central nervous and cardiovascular systems if given quickly. Hypertension, tachycardias, and seizures may be seen with rapid administration. Antagonism of narcotics is very short-lived. As such it is common for these drugs to wane and for renarcotization to occur. All opioids are controlled substances; their strict regulations for ordering, storage, and record keeping may make them problematic. Yet these drugs are essential for pain control and constitute the most effective drug therapies for acute, critical, emergent, and perioperative pain (Table 2-1). Fig. 2-1 illustrates a reasonable first approach for using opioids for acute pain management in emergent patients.

Table  2-1 Opioids for Critical Patient Management Opioid

Dosage

Fentanyl

0.005-0.02 mg/kg q2h IM, IV, SQ or in CRI 0.1-0.2 mcg/kg/min 1-3 mcg/kg IV, followed by 3-10 mcg/kg/h CRI because of extremely short initial bolus half-life 0.1-0.5 mg/kg q4-8h IM, SQ in dogs; 0.1-0.3 mg/kg q12-24h in cats; or in CRI 0.02-0.1 mg/kg/hr in both species 0.02-0.1 mg/kg q4-12h IV, IM, SQ 0.02-0.2 mg/kg q4-12 h IV, IM, SQ 5-10 mg/kg IM, SC q2-4h

Remifentanil

Morphine

Oxymorphone Hydromorphone Meperidine

CRI, Continuous-rate infusion; IM, intramuscularly; IV, intravenously; SQ, subcutaneously.

12

Section  I  Critical Care Emergency case arrives System triage Venous access Nova/Big 4 Stabilization (airway, oxygen, volume, pressure, ventilator status, temperature, electrolyte, CNS status Injury, insult, or wound (SPICE) (Stabilization, Protection and Pressure, Ice and Immobilization, Compression, Elevation) Baseline pain score Pain yes

Pain no

Administer pure Mu agonist opioid �/� benzodiazepine1

Reassess in 15-30 min

Reassess pain score and stabilization within 1/2-1 hr Pain yes

and Pain no

Anxiety score

Microdose Acep2 Benzodiazepine2 Microdose Alpha-two agent2

Moderate pain

Severe pain

Repeat pure Mu agonist opioid

Repeat pure Mu agonist opioid

Reassess for other sources of pain; reassess circulatory (pressure and volume), respiratory, CNS status And choose one or more of the following agents listed below Mild pain Choose one from each category TOPICAL AGENTS: Lidocaine in sterile lube Lidocaine patch Pramoxine 1% Silver sulfadiazine 2% Diphenhydramine

STABLE

UNSTABLE

NSAIDS: Meloxicam 0.1 mg/kg IV Carprofen 2.2 mg/kg SQ ALPHA AGONISTS: Medetomidine 2 mcg/kg IV Na CHANNEL BLOCK: Lidocaine CRI7

OPIOIDS: Buprenorphine 0.02 mg/kg IV, IM or SQ q. 6-8 hr Fentanyl patch application with repeat original opioid q. 4-8 hr ADJUNCT ORAL MEDICATIONS: Gabapentin 3-5 mg/kg PO q. 12 hr Tramadol 2-4 mg/kg PO q. 12 hr (dogs) 1-2 mg/kg PO q. 24 hr (cats) Amantadine 3-5 mg/kg PO SID Acetaminophen 5 mg/kg PO (dogs only) IF STABLE: Meloxicam 0.2 mg/kg PO, IV, SQ q. 24 hr (dogs), q. 48-72 hr (cats) Carprofen 2.2 mg/kg PO, SQ q. 12 hr (dogs), q. 48-72 hr (cats)

NMDA ANTAGONIST: Ketamine 1-2 mg/kg IV, IM, SQ q. 1-3 hr OPIOIDS: Fentanyl CRI3

STABLE

UNSTABLE

NSAIDS: Meloxicam 0.1 mg/kg IV Carprofen 2.2 mg/kg SQ ALPHA AGONISTS: Medetomidine CRI5 Na CHANNEL BLOCK: Lidocaine CRI7

OPIOIDS: Fentanyl CRI3 Remifentanil CRI4 NMDA ANTAGONIST: Ketamine CRI6 COMBO INFUSIONS: MLK CRI8 FLK CRI9

Would a Locoregional Block be possible and appropriate?

Moderate pain Epidural Localized nerve or plexus blockade Cavitary (e.g., intrapleural) or wound block

Severe pain Epidural catheter Nerve or plexus catheter Wound soaker catheter Bupivicaine/Lidocaine/Morphine10 via catheter q. 4-8 hr or Lidocaine or Bupivicaine CRI via catheter11

Reassess critical system status and pain score q. 1-4 hr

α-2 Agonist Analgesics This class of drug warrants special attention because of its potent analgesic power at doses that are also capable of inducing profound sedation and cardiovascular changes. α-2 Agonists have quickly attained “sedative analgesic” status in veterinary medicine. Used at ultra-low doses (often called microdoses), these are useful adjunct analgesics, especially when combined with narcotics. Medetomidine has proven to be equal to or better as a short-term analgesic than buprenorphine, hydromorphone, or oxymorphone for control of pain in dogs. Sedative and analgesic effects are the result of activation of presynaptic and postsynaptic α-2 receptors, which decrease pain-related norepinephrine transmission. Most notable of α-2 agonist side effects are changes in heart rate and rhythm. Atrioventricular blocks, bradyarrhythmia, and sinus bradycardia are caused by vasoconstriction, decreased sympathetic output, and reflex increases in parasympathetic tone. These changes are even noticeable after microdosing. Arterial blood pressure usually increases transiently and then decreases to normal or mildly decreased levels. Cardiac output decreases drastically as a result of lowered cardiac contractile force and stroke volume, which precludes the use of α-2 agents as first-line analgesics for acute pain, even though myocardial circulation may actually improve in some species. Since α-2 receptors modulate the release of insulin by the pancreas, hyperglycemia and resultant glycosuria are produced. Diuresis is also caused by an antiadrenocorticotropic hormone effect on the renal tubules. The coadministration of an opioid with medetomidine appears quite useful for enhanced sedation and analgesia well beyond that achieved with either drug alone. Medetomidine and dexmedetomidine should be used after volume and pressure stabilization, perisurgically, and always as microdose adjunct agents in the acute pain care setting (see Fig 2-1). Especially beneficial is the microdose of medetomidine (1 to 3 mcg/kg intravenously or intramuscularly, canine and feline) used to supplement pain relief provided by morphine, hydromorphone, or oxymorphone. Medetomidine brings a great benefit not appreciable with narcotic analgesics (i.e., stress reduction). Sympathetic

Chapter  2  Acute Pain Management 13 stimulation is useful in the very peracute initial stages of injury but quickly (within 12 hours) becomes detrimental. Since systemic effects of the stress response add not only to difficulty in controlling pain via any method but also to increased chances of chronic pain states through central hypersensitization and “wind-up,” blunting of this stress response can be extremely useful in poststabilization multimodal pain therapy. An added benefit of the α-2 agonists is the potential for rapid reversal in emergency or even titratable reversal with antagonist drugs such as atipamezole. Unlike reversal of the opioids, reversal of an α-2 agent is both complete and long lasting. Contraindications for α-2 agonists include untreated shock, hypotension, hypertension, overt bleeding, clinical bradyarrhythmias, Addison’s disease, and syncope. I use medetomidine as an adjunct agent with the following generalities: longer than 12 to 24 hours after initial insult (animal stabilized), in microdose form (Table 2-2) alternating between intermittent doses of narcotic or as a CRI, and, finally, only in patients capable of tolerating mild-to-moderate reduction of cardiac output. These drugs should not be used in patients experiencing shock or cardiovascular collapse.

Table  2-2 Commonly Used a-2 Agonists a-2 Agonist

Dosage

Dexmedetomidine

Dog: 0.001-0.003 mg/kg q4-6 h SQ, IM, IV Cat: 0.003-0.01 mg/kg q4-6 h SQ, IM, IV Both species: continuous-rate infusion of 0.2-2 mcg/kg/hr Dog: 0.001-0.005 mg/kg q 4-6 hr SQ, IM, IV Cat: 0.003-0.01 mg/kg q.4-6 hr SQ, IM, IV Both species: continuous rate infusion of 0.2-2 mcg/kg/hr

Medetomidine

Fig. 2-1  Flow chart for acute pain management in the emergent patient. 1Pure Mu agonists: Hydromorphone 0.05 to 0.1 mg/kg IV, IM, SQ; oxymorphone 0.1 to 0.2 mg/kg IV, IM, SQ; morphine 0.1 to 0.5 mg/kg IM; fentanyl 3 to 10 mcg/kg IV, IM, SQ. Benzodiazepines: Midazolam 0.3 to 0.5 mg/kg IV, IM, SQ; diazepam 0.2 to 0.5 mg/kg IV. SQ administration should be avoided in emergent, acute, and critical-care patients. 2 Microdose anxiolytics: Acepromazine 0.01 to 0.05 mg/kg IV, IM, SQ not to exceed 0.3 mg in cats and 1 mg in dogs; diazepam and midazolam at doses noted in footnote 1; medetomidine or dexmedetemidine 1 to 3 mcg/kg IV, IM, SQ. 3 Fentanyl continuous-rate infusion (CRI): 0.02 to 0.2 mcg/kg/min. 4 Remifentanil CRI: 1 to 2 mcg/kg/hr; monitor ventilatory status cautiously in patients on remifentanil CRI. (MM Flores, personal communication.) 5 Medetomidine CRI: 0.02 to 2 mcg/kg/hr. 6 Ketamine CRI: 5 to 20 mcg/kg/min. 7 Lidocaine CRI: dog: 50 to 100 mcg/kg/min. 8 MLK CRI: see Table 2-4, drug calculator located at http://www.vasg.org/constant_rate_infusions.htm, or morphine 0.1 mg/kg/hr, lidocaine 50 mcg/kg/min, ketamine 10 mcg/kg/min (for cats delete lidocaine). (Courtesy of Dr. Robert Stein, DVM, DAAPM and Dr. David Thompson, DVM.) 9 FLK CRI: Fentanyl 0.1 mcg/kg/min; lidocaine 50 mcg/kg/min; ketamine 10 mcg/kg/min (for cats, delete lidocaine). 10 Intermitent injections via epidural catheter: 0.1 mg/kg morphine in 0.2 mg/kg bupivacaine with or without saline not to exceed 0.2 ml/kg total volume; intermittent injections via peripheral nerve catheters: 0.1 to 0.2 mg/kg bupivacaine with or without 0.2 to 1 mg/kg lidocaine with or without 0.01 mg/kg morphine with or without saline to expand for plexus coverage. 11 CRIs via epidural catheter 0.05 mg/kg/hr bupivacaine or ropivacaine in 0.05 mg/kg/hr morphine.

14

Section  I  Critical Care

Nonsteroidal Antiinflammatory Drugs NSAIDs, classically used to treat chronic pain and inflammation, have taken on a new role in treatment of perioperative and acute pain. Potent oral and parenteral forms of these drugs compare favorably with opioids for treatment of acute inflammation and pain. Although multiple modes of action are proposed, most NSAIDs act by inhibiting the enzyme system cyclooxygenase (COX), an enzyme found in at least three forms (-1, -2, -3), prostanoids such as thromboxane, prostacyclin, prostaglandin (PG)E2, PGF2, and PGD2. These prostanoids serve as mediators of inflammation and amplifiers of nociceptive input and transmission. They also affect homeostatic functions such as platelet adhesion, gastric epithelium turnover, renal vasodilation, and bronchodilation. Lipoxygenase (LOX), another enzyme inhibited by some NSAIDs, also acts on arachidonic acid to form eicosatetranoic acids and leukotrienes. All NSAIDs currently available inhibit COX-2, some avoid inhibition of COX-1 (coxibs), and some also act on LOX (tepoxalin). No single NSAID is substantially more effective than another at treating either acute or chronic pain. COX-1–sparing drugs are not inherently more effective than COX-1–inhibiting drugs. There are definite and relative contraindications for the use of NSAIDs similar to those directed against the α-2 agents. NSAIDs should not be administered to patients with renal or hepatic insufficiency, dehydration, hypotension, conditions associated with low circulating volume (congestive heart failure, unregulated anesthesia, shock), or evidence of ulcerative GI disease. The vascular volume, tone, and pressure of trauma patients should be completely stabilized before the use of NSAIDs. Patients receiving concurrent administration of other NSAIDs or corticosteroids or those considered to be cushingoid should not receive parenteral NSAIDs, especially in emergent or acute situations. In addition, NSAIDs should not be used for patients with coagulopathies, particularly those that are caused by platelet number or function defects, or factor deficiencies, or for those with asthma or other bronchial disease. Where does this leave us in terms of the acutely injured, traumatized, and emergent patient? The administration of NSAIDs should ONLY be considered in the well-hydrated, normotensive dog or cat with normal renal or hepatic function, no hemostatic abnormalities, and no concurrent steroid administration. Furthermore, although opioids and α-2 agonists seem to have an immediate analgesic effect, most NSAIDs take up to 30 minutes for a more subtle effect to be recognized. Thus NSAIDs are not first-line analgesics. However, their importance as part of the multimodal regimen should not be understated. NSAIDs are devoid of many of the side effects of narcotic administration and, compared to corticosteroids, do not suppress the pituitary-adrenal axis. NSAIDs are useful in treating initial tissue injury and suppressing central hypersensitization within the dorsal horn of the spinal cord, a phenomenon known to perpetuate chronic pain states. These drugs are most useful in cases of orthopedic trauma, skin trauma, and appendicular soft-tissue bruising once stabilization of volume status and assessment of coagulation and renal function have occurred (see Fig 2-1). Cats are susceptible to the toxic effects of many NSAIDs because of slow clearance and dose-dependent

Table  2-3 Commonly used NSAIDs NSAID

Dosage

Carprofen

Dogs: 2-4 mg/kg PO, IM, IV, SQ q12h; cats: q48-72h Dogs and cats: 0.5-1 mg/kg IM, SQ, IV q24-48h for three doses Dogs: 0.5-1 mg/kg PO, IM, IV, SQ q12h; cats: q48-72h Dogs: 0.1-0.2 mg/kg q24h; cats 0.1 mg/ kg q48-72h

Flunixin meglumine Ketoprofen Meloxicam

IM, Intramuscularly; IV, intravenously; SQ, subcutaneously; NSAID, nonsteroidal antiinflammatory drug.

elimination secondary to deficient glucuronidation in this species. However, this species difference is not a contraindication to NSAID administration, especially when dealing with acute pain. Simply, both the dose and the dosing interval of most commonly used NSAIDs needs to be altered for these drugs to be used safely in cats. In both canine and feline patients carprofen and meloxicam have impressive safety records compared to older injectable NSAIDs such as flunixin meglumine and ketoprofen. Nonloading (nonlabel) doses of either agent (Table 2-3) are preferred for acute multimodal therapy. Unlike opioids or α-2 agents, NSAIDs can be continued in the postacute care setting in oral forms.

Local and Regional Techniques of Pain Relief for the Acutely Painful Patient Local anesthetics may be administered epidurally, intrathoracically, intraperitoneally, and intraarticularly. Lidocaine and bupivacaine are the most commonly admini­ stered local anesthetics. Lidocaine provides for quick, short-acting sensory and motor impairment. Bupivacaine provides for later-onset, longer-lasting desensitization without motor impairment. Combinations of the two agents diluted with saline are frequently used to provide for quick-onset analgesia with little motor impairment that lasts between 4 and 6 hours in most patients. Epinephrine-free solutions are recommended, especially in emergent patients. Placement of anesthetic close to nerves, roots, or a plexus is improved with the use of a stimulating nerve locator. Excellent reference to nerve localization for locoregional blockade is provided at www. ivis.org (see references). Cats seem to be more sensitive to the effects of local anesthetics, and the lower ends of most dosage ranges are safest for blockade in this species. Local and regional techniques block the initiation of noxious signals, thereby effectively “preventing” pain from entering the central nervous system. Frequently the neurohormonal response that is stimulated in both pain and stress is blunted as well. Overall the patient has less local and systemic adverse effects of pain, disease processes are minimized, chronic pain states are unlikely, and outcome is improved. Regional techniques are best applied as part of an analgesic regimen that consists of continuous

administration, narcotics (with or without α-agonists), NSAIDs, anxiolytics, and good nursing (see Fig. 2-1). Extended-release (lipid-encapsulated) local anesthetics and opioids, recently available in human pain medicine, may make neuraxial and perineural catheterization unnecessary for long-term regional blockade. Topical and Infiltrative Blockade Lidocaine can be added to sterile lubricant in a oneto-one concentration to provide decreased sensation for urinary catheterization, nasal catheter insertion, minor road burn analgesia, and pyotraumatic dermatitis analgesia. Proparacaine is a topical anesthetic useful for corneal or scleral injuries. Local anesthetics can be infiltrated into areas of tissue trauma by using longterm continuous drainage catheters and small portable infusion pumps (www.milaint.com, www.bbraunusa. com). This is a very effective method of providing days of analgesia for massive surgical or traumatic soft-tissue injury. Even without the catheter, incisional or regional soft-tissue blocking using a combination of 1 to 2 mg/kg of lidocaine and 0.5 to 2 mg/kg of bupivacaine diluted with equal volume of saline is effective for infiltrating or “splash” blockading large areas of injury for 3 to 6 hours of analgesia. Cranial Nerve Blockade Administration of local anesthetic drugs around the infraorbital, maxillary, ophthalmic, mental, and alveolar nerves can provide excellent analgesia for dental, orofacial, and ophthalmic trauma and surgical procedures. Each nerve may be desensitized by injecting 0.1 to 0.3 ml of a 2% lidocaine hydrochloride solution and 0.1 to 0.3 ml of a 0.5% bupivacaine solution using a 1.2- to 2.5-cm, 22- to 25gauge needle. Precise placement (perineurally versus intraneurally with painful neuroma formation common with the latter) is enhanced by using catheters in the foramen versus simple needle administration. Aspiration should always be performed before administration of local agents to rule out intravascular injection. Intrapleural Blockade This block is used to provide analgesia for thoracic, lower cervical, cranial abdominal (gastric, hepatic, and pancreatic pain), and diaphragmatic pain. Following aseptic preparation, a small through-the-needle 20- to 22-gauge catheter is placed in the thoracic cavity between the seventh and ninth intercostal space on the midlateral aspect of the thorax. A 0.5- to 1-mg/kg dose of lidocaine and a 0.2- to 0.5-mg/kg dose of bupivacaine dose are aseptically mixed with a volume of saline equal to the volume of bupivacaine and slowly injected over a period of 2 to 5 minutes following aspiration to ensure no intravascular injection. Depending on the lesion, the patient should be positioned to allow the intrapleural infusion to “coat” the area. Most effective is positioning the patient in dorsal recumbency (if injury allows) for several minutes following the block to make sure that local anesthetic occupies the paravertebral gutters and thus the spinal nerve roots. The block should be repeated every 3 hours in dogs and every 8 to 12 hours in cats. The catheter is secured to the skin surface and capped for repetitive administration.

Chapter  2  Acute Pain Management 15 Brachial Plexus Blockade Administration of local anesthetic around the brachial plexus provides excellent analgesia for forelimb surgery, particularly that distal to the shoulder, and for amputations. Nerve-locator guided techniques are much more accurate and successful than “blind” placement of local anesthetic; however, even the latter is very useful for forelimb injuries. Aseptic preparation is performed over a small area of skin near the point of the shoulder. A 22gauge, 1.5- to 3-inch spinal needle is inserted medial to the shoulder joint, axial to the lesser tubercle, and advanced caudally, medial to the body of the scapula and toward the costochondral junction of the first rib. Aspiration ensures avascular injection of one third of the volume of local anesthetic mix. The needle is withdrawn slightly and then “fanned” dorsally and ventrally while the remaining solution is injected. Local anesthetic doses are similar to those for intrapleural blockade. Epidural Anesthesia and Analgesia Epidural analgesia refers to the injection of an opioid, a phencyclidine, an α-agonist, or an NSAID into the epidural space, whereas epidural anesthesia refers to the injection of only local anesthetic. In most patients a combination of the two is used. Epidurals are used for a variety of acute and chronic painful conditions, including surgery or trauma in the pelvis, hind limbs, abdomen, and thorax; amputations of forelimbs and hind limbs; tail or perineal procedures; C-sections; diaphragmatic hernia repairs; pancreatitis; peritonitis; and disk disease. Epidurals performed using opioids or less than 0.25% bupivacaine will not result in hind limb paresis or decreased urinary or anal tone (incontinence). Lidocaine or mepivacaine epidurals are prone to these side effects. Morphine is also one of the most useful opioids for administration in the epidural space because of its slow systemic absorption. Epidural catheters used for the instillation of drugs either through CRI or intermittent injection can be placed in both dogs and cats. Routinely placed through the lumbosacral space, these catheters are used with cocktails, including preservative-free morphine, bupivacaine, medetomidine, and ketamine. This therapy is effective for preventing “windup” pain in the peritoneal cavity or the caudal half of the body. Catheters may be maintained for 7 to 14 days if placed aseptically. The animal is positioned in lateral or sternal recumbency. Sterile preparation is performed over the lumbosacral site. A 20- to 22-gauge 1.5- to 3-inch spinal or epidural needle is advanced through the skin caudal to the spine of L7. The skin penetration site is found by palpating the craniodorsal-most extent of the wings of the ilium bilaterally and drawing an imaginary line between them. The spine of L7 is located immediately behind this line. The site of entry is caudal to the spine. Entry into the epidural space is noted by loss of resistance or observing a drop of saline meniscus being pulled into the space. I prefer bupivacaine 0.1- to 0.3-mg/kg (motor sparing is less than 0.3%) with morphine 0.1 mg/kg for canine patients. This can be diluted to a total volume of 0.1 to 0.15 ml/kg with saline if advancement of the solution into the thoracic area is needed (e.g., thoracotomy, forelimb amputation, diaphragmatic repair). Total volume rarely exceeds 6 ml of

16

Section  I  Critical Care

saline, local and opioid combined for dogs. This calculation is appropriate for an injection made from the lumbosacral space. Injections made more cranial are reduced in volume by 25% per four to five vertebral bodies. For cats 0.1 mg/kg of morphine is diluted with saline to a total volume of 0.1 to 0.2 ml/kg. Local anesthetic is rarely used because of the propensity to administer it into the subarachnoid space and the increased toxicity potential in this species.

Adjunct Agents and Techniques for Acute Pain Over the past decade scores of other medications have been used to assist with analgesia in both critical and emergent patients. Ketamine was classically considered a dissociative anesthetic, but it also has potent activity as an N-methyl-D-aspartate receptor antagonist. This receptor located in the central nervous system mediates windup and central sensitization (a pathway from acute to chronic pain). Blockade of this receptor with microdoses of ketamine results in the ability to provide body surface, somatic, and skin analgesia and to potentially lower doses of opioids and α-agonists. Loading doses of 0.5 to 2 mg/ kg are used intravenously initially and continued with CRIs of 2 to 20 mcg/kg/minute. High doses can aggravate, sensitize, or excite the animal in subacute or acute pain. Tramadol is an analgesic that possesses both weak mu opioid agonist activity and norepinephrine and serotonin reuptake inhibition. It is useful for mild-to-moderate pain when given orally at doses of 1 to 10 mg/kg PO SID/TID. Cats appear to require only once-a-day dosing, and some are intolerant of doses over 1 to 2 mg/kg/ day. Regardless of its affinity for the opioid receptors, its true mechanism of action in companion animals remains largely unknown. Gabapentin is a synthetic analog of γ-aminobutyric acid. Originally introduced as an antiepileptic drug, its mechanism of action appears to be modulation of calcium channels. It is among a number of commonly used antiepileptic medications, including pregabalin, carbamazepine, and lamotrigine, that are used to

treat central pain in humans. The rationale is their ability to suppress discharge in pathologically altered neurons. Chronic, burning, neuropathic, and lancinating pain (neuropathic pain) in small animals responds well to 3 to 10 mg/kg PO daily. Ever since the introduction of local anesthetics, it has been common for clinicians to use drugs that block ion channels control pain. Sodium channels in particular are overexpressed in certain chronically inflamed tissues, particularly nervous tissue. Lidocaine is a local anesthetic. When given intravenously at a CRI, it is also effective in the treatment of acute and chronic pain. Side effects are minimal at a rate of 1 to 10 mcg/kg/minute for cats and 50 to 75 mcg/kg/minute in dogs. Pain relief in humans after even a brief IV infusion lasts many hours and sometimes even days. Acute pain is commonly treated in many postsurgical care units with MLK infusions (i.e., infusions containing standard amounts and rates of morphine, lidocaine, and ketamine). An example of one such infusion is included in Table 2-4. Lidocaine patches have been used for body surface, somatic, and skin pain in both cats and dogs. Patches come in 5% pliable, easily applicable, and moldable form; however, there is some concern about their adhesiveness in small animals, partially on haired skin. They are best applied to appendages and bandaged in place because of their inconsistent adhesive nature. In humans they appear to have a 12-hour life span, and recommendation is for removal before placement of another patch. Blood levels of lidocaine and by-products are not appreciated in either cats or dogs at this time. Likewise, potential for toxicity is low even in cats. Unlike fentanyl, there is little concern for respiratory depression, narcosis, or sedation in the patient or if human exposure occurs. These patches can also be cut and molded to fit an area of pain. I have used them on axial and appendicular structures for soft-tissue and bone pain, burns, road rash, hot spots, sprains, and strains at the following dosing scale (cats: ¼ to ½ 5% lidocaine patch q24 h; dogs: ¼ to 15% lidocaine patch q12 h). The patch should be removed for a minimum of 12 hours before application

Table  2-4 Morphine, Lidocaine, Ketamine (MLK) Continuous-Rate Infusion Formula for Perisurgical Analgesia All milliliters of solution noted below are added to a 500-ml bag of balanced isotonic crystalloid fluids (avoid fluids containing lactate) after equal volumes of original solution are removed from the bag. If rate of delivery of final solution is maintenance rate of 60 ml/kg/day or 2.5 ml/kg/hour, the following analgesic rates will be administered: morphine 0.12 mg/kg/hour, lidocaine 50 mcg/kg/minute, and ketamine 10 mcg/kg/minute. If higher rates of intravenous fluids are required, additional nonadditive bags should be used to avoid overadministration or toxicity of constituent analgesics. For cats, avoid lidocaine as part of continuous-rate infusion (CRI). I prefer reduction of each analgesic by half (milligram and milliliter amount) per 24 hours to avoid rebound pain from sudden CRI cessation.

Concentration (mg/ml) Morphine Lidocaine Ketamine

15 20 100

Milliliters of Analgesic to Add to 500 ml of Crystalloid Fluids   1.6 30   1.2

Total Milligrams of Analgesic Used (ml × concentration) 24 600 120

Total Milliliters of Crystalloid To Remove From 500-ml Bag Before Addition of Analgesics 32.8 ml total = (1.6 ml + 30 ml + 1.2 ml)

of a second patch. Mexiletine (4 to 10 mg/kg PO), an oral sodium channel blocker, can be used as an alternative to IV lidocaine for this background provision of analgesia. Many physical therapy modalities are safe and can provide excellent analgesia for the patient in acute pain. The acronym of PRICE (protection, rest, ice, compression, and elevation), which applies to many acute musculotendinous injuries in human athletes, likely also fits many of our patients in acute pain. Patients in acute pain treated with both immobilization of the injured area (modified Robert Jones’s bandage or a temporary splint) and cold compression have greater analgesia and less long-term inflammatory damage. Primary physiologic benefits of cold therapy are decreased local circulation, decreased pain, and decreased tissue extensibility. Cold therapy compressed onto the injury site is one of the single most frugal means of providing immediate analgesia for acute injury. Analgesia goes hand-in-hand with solid nutrition, basic nursing care, attention to anxiety and stress, GI function, movement and motion, bladder and bowel control, and emotional state. Analgesia is also provided by getting an animal to its home environment as soon as possible, allowing family interaction and housemate socialization, and appropriate exercise and stimulation. These simple techniques and care concepts can prevent and reduce pain in the acute and chronically ill patient.

References and Suggested Reading American College of Veterinary Anesthesiology: American College of Veterinary Anesthesiologists’ position paper on the treatment of pain in animal, J Am Vet Med Assoc 213:628, 1998. Campoy LC: Fundamentals of regional anesthesia using nerve stimulation in the dog. In Gleed RD, Ludders JW, editors: Recent advances in veterinary anesthesia and analgesia: companion animals, available at www.ivis.org. Clark MR: Antidepressants. In Wallace MS, Staats PS, editors: Pain medicine and management, New York, 2005, McGraw Hill, p 52. Gambling D et al: A comparison of DepoDur, a novel, singledose extended-release epidural morphine, with standard epidural morphine for pain relief after lower abdominal surgery, Anesth Analg 100:1065, 2005.

Chapter  2  Acute Pain Management 17 Gelinas C et al: Validation of the critical care pain observation tool in adult patients, Am J Crit Care 15:420, 2006. Granholm M et al: Evaluation of the clinical efficacy and safety of dexmedetomidine or medetomidine in cats and their reversal with atipamezole, Vet Anaesth Analg 33:214, 2006. Hansen BD: Analgesia and sedation in the critically ill, J Vet Emerg Crit Care 15:285, 2005. Hellebrekers LJ, Murrell JC: Post-operative analgesia in dog, Proceedings from the 8th World Congress of Veterinary Anesthesia, Knoxville, Tennessee, 2003, p 21. Hellyer P: Objective, categoric methods for assessing pain and analgesia. In Gaynor JS, Muir WW, editors: Handbook of veterinary pain management, St Louis, 2002, Mosby, p. 82. Holton LL et al: Development of a behaviour-based scale to measure acute pain in dogs, Vet Rec 148:525, 2001. Holton LL et al: Comparison of three methods used for assessment of pain in dogs, J Am Vet Med Assoc 212:61, 1998. Lome B: Acute pain and the critically ill trauma patient, Crit Care Nurs Q 28:200, 2005. Marino PL: The ICU book, ed 2, Baltimore, 1998, Williams & Wilkins. Matthews KA: Pain management for the critically ill parts I and II, Proceedings from the Western Veterinary Conference, 2004, Las Vegas, NV. Melzack R, Wall PD: Handbook of pain management, Philadelphia, 2003, Elsevier, p11. Quandt JE, Lee JA, Powell LL: Analgesia in critically ill patient, Compend Cont Educ Pract Vet 23: 433, 2005. Smith LJ et al: A single dose of liposome-encapsulated oxymorphone or morphine provides long-term analgesia in an animal model of neuropathic pain, Comp Med 53:280, 2003. Stanik-Hutt JA et al: Pain experiences of traumatically injured patients in a critical care setting, Am J Crit Care 10:252, 2001. Visser EJ: A review of calcitonin and its use in the treatment of acute pain, Acute Pain 7:185, 2005.

Resources on the Web International Veterinary Academy of Pain Management: www.ivapm.org International Veterinary Information Society: www.ivis.org Veterinary Anesthesia Support Group: www.vasg.org

CHAPTER 

3

Nutrition in Critical Care Daniel L. Chan, Hertfordshire, United Kingdom

Rationale for Nutritional Support in Critical Illness Critical illness induces unique metabolic changes in animals that put them at high risk for malnutrition and its deleterious effects. In diseased states the inflammatory response triggers alterations in cytokines and hormone concentrations and shifts metabolism toward a catabolic state. In the absence of adequate food intake, the predominant energy source for the host is derived from accelerated proteolysis. Thus these animals may preserve fat deposits in the face of lean muscle tissue loss. Consequences of malnutrition include negative effects on wound healing, immune function, strength (both skeletal and respiratory), and ultimately overall prognosis. An important point in regard to nutritional support of hospitalized patients is that the immediate goal is not to achieve “weight gain,” per se, which mostly likely reflects shift in water balance, but rather to minimize further loss of lean body mass. Reversal of malnutrition hinges on resolution of the primary underlying disease. Provision of nutritional support is aimed at restoring nutrient deficiencies and providing key substrates for healing and repair.

Patient Selection As with any intervention in critically ill animals, nutritional support carries some risk of complications. The risk of complications most likely increases with the severity of the disease, and the clinician must consider many factors in deciding when to institute nutritional support. Of utmost importance, the patient must be cardiovascularly stable before any nutritional support is initiated. With reduced perfusion, processes such as gastrointestinal motility, digestion, and nutrient assimilation are altered; and feeding under such circumstances is likely to result in complications. Other factors that should be addressed before nutritional support include hydration status, electrolytes imbalances, and abnormalities in acidbase status. In animals that have been stabilized, careful consideration must be given to the appropriate time to start nutritional support. A previously held notion that nutritional support is unnecessary until 10 days of inadequate nutrition have elapsed is certainly outdated and unjustified. Commencing nutritional support within 3 days of hospitalization, even before determining the diagnosis of the underlying disease, is a more appropriate goal in most cases; however, other factors should also be considered and are discussed in the next section. 18

Nutritional Assessment Proposed indicators of malnutrition in animals include unintentional weight loss (typically greater than 10%), poor hair coat quality, muscle wasting, signs of inadequate wound healing, and hypoalbuminemia. However, these abnormalities are not specific to malnutrition and often occur late in the disease process. A greater emphasis is placed on evaluating overall body condition rather than simply noting body weight. The use of body condition scores (BCSs) has been shown to be reproducible and reliable and a clinically useful measure in nutritional assessment. Fluid shifts may significantly impact body weight, but BCSs are not affected by fluid shifts and therefore are helpful in assessing critically ill animals. In light of the limitations of assessing nutritional status, it is crucial to identify early risk factors that may predispose patients to malnutrition such as anorexia of greater than 5 days’ duration, serious underlying disease (e.g., severe trauma, sepsis, peritonitis, acute pancreatitis), and large protein losses (e.g., protracted diarrhea, draining wounds, or burns). Nutritional assessment also identifies factors that can impact the nutritional plan such as specific electrolyte abnormalities; the presence of hyperglycemia, hypertriglyceridemia, or hyperammonemia; or comorbid illnesses such as renal, cardiac or hepatic disease. In the presence of such abnormalities the nutritional plan should be adjusted accordingly to limit acute exacerbations of any preexisting condition. Finally, since many of the techniques required for implementation of nutritional support (e.g., placement of most feeding tubes, intravenous catheters for parenteral nutrition) necessitate anesthesia, the patient must be properly evaluated and stabilized before induction of anesthesia. When the patient is deemed too unstable for general anesthesia, temporary measures of nutritional support that do not require anesthesia (e.g., nasoesophageal tube placement, placement of peripheral catheters for partial parenteral nutrition) should be considered.

Nutritional Plan Providing nutrition should occur as soon as it is feasible, with careful consideration for the most appropriate route of nutritional support. Providing nutrition via a functional digestive system is the preferred route of feeding, and particular care should be taken to evaluate if the patient can tolerate enteral feedings. Even if the patient can only tolerate small amounts of enteral nutrition, this route of feeding should be pursued and supplemented with parenteral nutrition (PN) as necessary to meet the patient’s nutritional needs. However, if an animal

Chapter  3  Nutrition in Critical Care 19

demonstrates complete intolerance to being fed enterally, some form of PN should be provided. Implementation of the devised nutritional plan should also be gradual, with the goal of reaching target level of nutrient delivery in 48 to 72 hours. Adjustments to the nutritional plan are made on the basis of reassessment and the development of any complications.

Calculating Nutritional Requirements Based on indirect calorimetry studies in dogs, there has been a recent trend of formulating nutritional support simply to meet resting energy requirements (RERs) rather than more generous illness energy requirements (IERs). For many years clinicians used to multiply the RER by an illness factor between 1.1 and 2 to account for purported increases in metabolism associated with different disease states. However, less emphasis is now being placed on these extrapolated factors, and the current recommendation is to use more conservative energy estimates (i.e., start with the animal’s RER) to avoid overfeeding and its associated complications. Examples of complications resulting from overfeeding include gastrointestinal intolerance, hepatic dysfunction, and increased carbon dioxide production. Although several formulas are proposed to calculate the RER, a widely used allometric formula can be applied to both dogs and cats of all weights. The formula most commonly used by the author is: RER = 70 × (current body weight in kilograms)0.75 Alternatively, for animals weighing between 3 and 25 kg, the following may be used: RER = (30 × current body weight in kilograms) + 70 In regard to protein requirements, hospitalized dogs should be supported with 4 to 6 g of protein per 100 kcal (15% to 25% of total energy requirements), whereas cats are usually supported with 6 or more g of protein per 100 kcal (25% to 35% of total energy requirements). In most cases estimation of protein requirements is based on clinical judgment and recognition that in certain disease states (e.g., peritonitis and draining wounds) protein requirements are markedly increased. 

Parenteral Nutritional Support PN can be delivered via a central vein (total PN [TPN]) or a peripheral vein (peripheral or partial PN [PPN]). TPN commonly refers to providing all of the animal’s calorie and protein requirements via the intravenous route. PPN is reserved when the PN supplies only part of the animal’s energy, protein, and other nutrient requirements. Because TPN supplies all of the animal’s calorie and protein requirements, it is often the modality of choice for animals that cannot tolerate enteral feeding. The disadvantages are that it requires a jugular venous catheter, it is more expensive (typically about 15% to 25% more for a TPN solution compared to a PPN solution for the same-size animal), and it may be associated with more metabolic complications.

PPN may be an alternative to TPN in selected cases, but it is important to be aware that it will not provide all of the animal’s requirements. Both TPN and PPN are typically a combination of dextrose, an amino acid solution, and a lipid solution. However, the concentration of some components (i.e., dextrose) varies, depending on whether TPN or PPN is chosen. Crystalline amino acid solutions are an essential component of PN. The importance of supplying amino acids relates to the maintenance of positive nitrogen balance and repletion of lean body tissue, which may be vital in the recovery of critically ill patients. Supplementation of amino acids may support protein synthesis and spare tissue proteins from being catabolized via gluconeogenesis. The most commonly used amino acid solutions (e.g., Travasol, Clintec Nutrition, Deerfield, IL; Aminosyn II, Abbott Laboratories, North Chicago, IL) contain most of the essential amino acids for dogs and cats, with the exception of taurine. However, as PN is typically not used beyond 10 days, the lack of taurine does not become a problem in most circumstances. Amino acid solutions are available in different concentrations from 4% to 15%, but the most commonly used concentration is 8.5%. Amino acid solutions are also available with and without electrolytes. Lipid emulsions are the calorically dense component of PN and a source of essential fatty acids. Lipid emulsions are isotonic and available in 10% to 30% solutions (e.g., Intralipid, Clintec Nutrition, Deerfield, IL; Liposyn III, Abbott Laboratories, North Chicago, IL). These commercially available lipid emulsions are made primarily of soybean and safflower oil and provide predominantly long-chain polyunsaturated fatty acids, including linoleic, oleic, palmitic, and stearic acids. The emulsified fat particles are comparable in size to chylomicrons and are removed from the circulation via the action of peripheral lipoprotein lipase. A common misconception exists in regard to the use of lipids in cases of pancreatitis. Although hypertriglyceridemia may be a risk factor for pancreatitis, infusions of lipids have not been shown to increase pancreatic secretion or worsen pancreatitis and therefore are considered safe. However, the one exception is in cases in which serum triglycerides are elevated, indicating a clear failure of triglyceride clearance. Although specific data regarding the maximal safe level of lipid administration in veterinary patients is not available, it would seem prudent to maintain normal serum triglyceride levels in patients receiving PN. Another concern surrounding the use of lipids in PN is their purported immunosuppressive effects via impairment of the reticuloendothelial system, particularly in PN solutions containing a high percentage of lipids. Despite in vitro evidence supporting the notion that lipid infusions can also suppress neutrophil and lymphocyte function, studies have not yet correlated lipid use and increased rates of infectious complications. Electrolytes, vitamins, and trace elements also may be added to the PN formulation. Depending on the hospital and the individual patient, electrolytes can be added to the admixture, included as part of the amino acid solution, or left out altogether and managed separately. As B vitamins are water soluble, they are more likely to become deficient in patients with high-volume diuresis

20

Section  I  Critical Care

(e.g., renal failure, diabetes mellitus), and supplementation could be considered. Since most animals receive PN for only a short duration, fat-soluble vitamins usually are not limiting; therefore supplementation is not usually required. The exception is in obviously malnourished animals in which supplementation may be necessary. Trace elements serve as cofactors in a variety of enzyme systems and can become deficient in malnourished patients as well. In humans receiving PN, zinc, copper, manganese, and chromium are routinely included in the PN admixture. These are sometimes added to PN admixtures for malnourished animals, but their compatibility with the solution must be verified. The addition of other parenteral medications to the PN admixture is possible; however, their compatibility must also be verified. Drugs that are known to be compatible and sometimes added to PN include heparin, insulin, potassium chloride, and metoclopramide. Although the addition of insulin to PN is often necessary in humans receiving PN, the hyperglycemia seen in veterinary patients with PN usually does not require insulin administration, except for diabetic patients that will require adjustments to their insulin regimen.

Parenteral Nutrition Compounding Based on the nutritional assessment and plan, PN can be formulated according to the worksheets found in Boxes 3-1 and 3-2. For TPN (Box 3-1) the first step is the calculation of the patient’s RER. Protein requirements (grams of protein required per day) are then calculated, taking into consideration factors such as excessive protein losses or severe hepatic or renal disease. The energy provided from amino acids is accounted for in the energy calculations and subtracted from the daily RER to estimate the total nonprotein calories required. Some protocols do not account for the energy provided by amino acids in the calculations, which may lead to overfeeding in critically ill animals. The nonprotein calories are then usually provided as a 50:50 mixture of lipids and dextrose; however, this ratio can be adjusted in cases of persistent hyperglycemia or hypertriglyceridemia (e.g., a higher proportion of calories would be given from lipids in an animal with hyperglycemia). The calories provided from each component (amino acids, lipids, and dextrose) are then divided by their respective caloric densities, and the exact amounts of each component are added to the PN bags in an aseptic fashion. The amount of TPN delivered often will provide less than the patient’s daily fluid requirement. Additional fluids can either be added to the PN bag at the time of compounding or be provided as a separate infusion. For formulation of PPN, Box 3-2 provides a step-bystep protocol in which patients of various sizes can receive 70% of their RER and approximately meet their daily maintenance fluid requirement. In very small animals (≤3 kg), the amount of PPN will exceed the maintenance fluid requirement and increase the risk for fluid overload; thus adjustments may need to be made. Also, in animals requiring conservative fluid administration (e.g., congestive heart failure), these calculations for PPN may provide more fluid than would be safe. This formulation has been

designed so that the proportion of each PN component depends on the weight of the patient, such that a smaller animal (between 3 and 5 kg) receives ­proportionally more calories from lipids compared to a large dog (>30 kg) that receives more calories in the form of carbohydrates. This allows the resulting formulation to approximate the patient’s daily fluid requirement. Ideally compounding of PN should be done aseptically under a laminar flow hood using a semiautomated, closed-system, PN compounder (e.g., Automix compounder, Clintec Nutrition, Deerfield, IL). If the appropriate facilities and equipment are not available, it may be preferable to have a local human hospital, compounding pharmacy, or human home health care company compound PN solutions using the formulations listed in Boxes 3-1 and 3-2. Alternatively, commercial ready-to-use preparations of glucose or glycerol and amino acids suitable for (peripheral) intravenous administration are available (e.g., ProcalAmine B, Braun Medical Inc., Irvine, CA). Although ready-to-use preparations are convenient, they provide only 30% to 50% of caloric requirements when administered at maintenance fluid rates and as a result should only be used for interim nutritional support or to supplement low-dose enteral feedings.

Parenteral Nutrition Administration The administration of any PN requires a dedicated catheter used solely for PN administration that is placed using aseptic technique. In most cases this requires placement of additional catheters since PN should not be administered through existing catheters that were placed for reasons other than PN. Long catheters composed of silicone, polyurethane, or tetrafluoroethylene are recommended for use with any type of PN to reduce the risk of thrombophlebitis. Multilumen catheters are often recommended for TPN because they can remain in place for long periods and separate ports can also be used for blood sampling and administration of additional fluids and intravenous medications without the need for separate catheters placed at other sites. Injections into the PN catheter infusion port or administration lines should be strictly prohibited. The high osmolarity of TPN solutions (often 1200 mOsm/L) requires its administration through a central venous (jugular) catheter, whereas PPN solutions can be administered through either a jugular catheter or catheters placed in peripheral veins. The concern with high osmolarity is that it may increase the incidence of thrombophlebitis, although this has not been well characterized in veterinary patients. Because of the various metabolic derangements associated with critical illness, TPN should be instituted gradually over 48 hours. Administration of TPN is typically initiated at 50% of the RER on the first day and increased to the targeted amount by the second day. In most cases PPN can be started without gradual increase. It is also important to adjust the rates of other fluids being concurrently administered. For both TPN and PPN, the animal’s catheter and infusion lines must be handled aseptically at all times to reduce the risk of PNrelated infections.

Chapter  3  Nutrition in Critical Care 21



Box  3-1 Worksheet for Calculating a Total Parenteral Nutrition Formulation 1. Resting energy requirement (RER) 70 × (current body weight in kg)0.75 = kcal/day or for animals 3-25 kg, can also use: 30 × (current body weight in kg) + 70 = kcal/day RER = _________kcal/day 2.  Protein requirements

Canine

Feline

Standard*

4-5 g/100 kcal

6 g/100 kcal

Decreased requirements* (hepatic/renal failure)

2-3 g/100 kcal

3-4 g/100 kcal

Increased requirements* (protein-losing conditions)

6 g/100 kcal

6 g/100 kcal

(RER ÷ 100) × _______________ g/100 kcal = _______________g of protein required per day (protein req) 3. Volumes of nutrient solutions required each day a.  8.5% amino acid solution = 0.085 g of protein per milliliter _______________ g of protein per day required ÷ 0.085 g/ml = _______________ ml of amino acids per day b. Nonprotein calories: The calories supplied by protein (4 kcal/g) are subtracted from the RER to get total nonprotein calories needed: _______________ g of protein required per /day × 4 kcal/g = _______________ kcal provided by protein RER − kcal provided by protein = _______________ nonprotein kcal needed per day c. Nonprotein calories are usually provided as a 50:50 mixture of lipid and dextrose. However, if the patient has a preexisting condition (e.g., diabetes, hypertriglyceridemia), this ratio may need to be adjusted. *20% lipid solution = 2 kcal/ml To supply 50% of nonprotein kcal _______________ lipid kcal required ÷ 2 kcal/ml = _______________ ml of lipid *50% dextrose solution = 1.7 kcal/ml To supply 50% of nonprotein kcal _______________ dextrose kcal required ÷ 1.7 kcal/ml = _______________ ml of dextrose 4. Total daily requirements _______________ ml of 8.5% amino acid solution _______________ ml of 20% lipid solution _______________ ml of 50% dextrose solution _______________ ml total volume of total parenteral nutrition solution 5.  Administration rate Day 1: _______________ ml/hr Day 2: _______________ ml/hr Day 3: _______________ ml/hr *Be sure to adjust the patient’s other fluids accordingly!

PN should be administered as continuous-rate infusions over 24 hours via fluid infusion pumps. Inadvertent delivery of massive amounts of PN can result if administration is not regulated properly. Once a bag of PN is set up for administration, it is not disconnected from the patient even for walks or diagnostic procedures—the drip regulator is decreased to a slow drip and accompanies the patient throughout the hospital. Administration of PN through a 1.2-micron in-line filter (e.g., 1.2-micron downstream filter, Baxter Healthcare Corp., Deerfield, IL)

is also recommended and is attached at the time of setup. This setup process is performed daily with each new bag of PN. Each bag should only hold 1 day’s worth of PN, and the accompanying fluid administration sets and inline filter are changed at the same time using aseptic technique. PN should be discontinued when the animal resumes consuming an adequate amount of calories of at least 50% of RER. TPN should be discontinued gradually over a 6- to 12-hour period, but PPN can be discontinued without weaning.

22

Section  I  Critical Care

Box  3-2 Worksheet for Calculating a Partial Parenteral Nutrition Formulation 1. Resting energy requirement (RER) 70 × (current body weight in kg)0.75 = kcal/day or for animals 3-25 kg, can also use: 30 × (current body weight in kg) + 70 = kcal/day RER = _______________kcal/day 2.  Partial energy requirement (PER) Plan to supply 70% of the animal’s RER with partial parenteral nutrition (PPN): PER = RER × 0.70 = _______________kcal/day 3. Nutrient composition (note: For animals ≤3 kg, the formulation will provide a fluid rate higher than maintenance fluid requirements. Be sure that the animal can tolerate this volume of fluids) a. Cats and dogs 3-5 kg: PER × 0.20 =_______________ kcal/day from carbohydrate PER × 0.20 =_______________ kcal/day from protein PER × 0.60 =_______________ kcal/day from lipid b. Cats and dogs 6-10 kg: PER × 0.25 =_______________ kcal/day from carbohydrate PER × 0.25 =_______________ kcal/day from protein PER × 0.50 =_______________ kcal/day from lipid c. Dogs 11-30 kg: PER × 0.33 =_______________ kcal/day from carbohydrate PER × 0.33 =_______________ kcal/day from protein PER × 0.33 =_______________ kcal/day from lipid d. Dogs >30 kg: PER × 0.50 =_______________ kcal/day from carbohydrate PER × 0.25 =_______________ kcal/day from protein PER × 0.25 =_______________ kcal/day from lipid 4. Volumes of nutrient solutions required each day a.  5% dextrose solution = 0.17 kcal/ml _______________ kcal from carbohydrate ÷ 0.17 kcal/ml = _______________ml of dextrose per day b.  8.5% amino acid solution = 0.085 g/ml = 0.34 kcal/ml _______________ kcal from protein ÷ 0.34 kcal/ml = _______________ml of amino acids per day c. 20% lipid solution = 2 kcal/ml _______________ kcal from lipid ÷ 2 kcal/ml = _______________ ml of lipid per day 5. Total daily requirements _______________ ml of 5% dextrose solution _______________ ml of 8.5% amino acid solution _______________ ml of 20% lipid solution _______________ ml of total volume of PPN solution 6. Administration rate This formulation provides an approximate maintenance fluid rate. _______________ ml/hour of PPN solution *Be sure to adjust the patient’s other fluids accordingly!



Enteral Nutritional Support In critically ill animals with a functional gastrointestinal tract, the use of feeding tubes is the standard mode of nutritional support. As discussed previously, a key decision is determining whether the patient can undergo general anesthesia for placement of feeding tubes. In animals with surgical disease requiring laparotomy, placement of gastrostomy or jejunostomy feeding tubes should receive particular consideration. Feeding tubes commonly used in critically ill animals are nasoesophageal, esophagostomy, gastrostomy, and jejunostomy. The decision to choose one tube over another is based on the anticipated duration of nutritional support (e.g., days versus months), the need to circumvent certain segments of the gastrointestinal tract (e.g., oropharyngeal injury, esophagitis, pancreatitis), clinician experience, and suitability of patient to withstand anesthesia (very critical animals may only tolerate placement of nasoesophageal feeding tubes). More in-depth information of the various feeding tube options is discussed elsewhere in this text (see Chapter 136).

Monitoring for Complications Because the development of complications in critically ill animals can have serious consequences, an important aspect of nutritional support involves close monitoring. With implementation of enteral nutrition, possible complications include vomiting, diarrhea, fluid overload, electrolyte imbalances, feeding tube malfunction, and infectious complications associated with insertion sites of feeding tubes. Metabolic complications are more common with PN and include the development of hyperglycemia, lipemia, azotemia, hyperammonemia, as well as electrolyte abnormalities. Rarely nutritional support can be associated with severe abnormalities that are sometimes referred to as the refeeding syndrome. Strategies to reduce risk of complications include observing aseptic techniques when placing feeding tubes and intravenous catheters, using conservative estimates of energy requirements (i.e., RER), and careful patient monitoring. Parameters that should be monitored during nutritional support include body temperature; respiratory rate and effort; signs of fluid overload (e.g., chemosis, increased body weight); and serum concentrations of glucose, triglycerides, electrolytes, blood urea nitrogen, and creatinine. Detection of any abnormality should prompt full reassessment.

Pharmacologic Agents in Nutritional Support Since critically ill animals are often anorexic, there is the temptation to use appetite stimulants to increase food intake. Unfortunately appetite stimulants are generally unreliable and seldom result in adequate food intake in critically ill animals. Pharmacologic stimulation of appetite is often short-lived and only delays true nutritional support. I do not believe that appetite stimulants have a place in the management of hospitalized animals when more effective measures of nutritional support such as placement of feeding tubes are more appropriate. The use of appetite stimulants may be considered in recovering

Chapter  3  Nutrition in Critical Care 23 animals once they are home in their own environment, since ideally the primary reason for loss of appetite should be reversed by time of hospital discharge.

Future Directions in Critical Care Nutrition The current state of veterinary critical-care nutrition revolves around proper recognition of animals in need of nutritional support and implementation of strategies to best provide nutritional therapies. Important areas that need further evaluation in critically ill animals include the optimal composition and caloric target of nutritional support, strategies to minimize complications, and optimize outcome. Recent findings implicating development of hyperglycemia with poor outcome in critically ill humans have led to more vigilant monitoring and stricter control of blood glucose, with obvious implications for nutritional support. Evidence of a similar relationship in dogs and cats is mounting, and ongoing studies are focusing on the possible consequences of hyperglycemia. Until further studies suggest otherwise, efforts to reduce the incidence of hyperglycemia in critically ill animals, especially those receiving nutritional support, should be strongly pursued. Other exciting areas of clinical nutrition in critically ill humans include the use of special nutrients that possess immunomodulatory properties such as glutamine, arginine, and n-3 fatty acids. In specific populations these agents used singly or in combination have demonstrated promising results, even in severely affected people. However, results have not been consistent, and ongoing trials continue to evaluate their efficacy. To date there is limited information on the use of these nutrients to specifically modulate disease in clinically affected animals. Future studies should focus on whether manipulation of such nutrients offer any benefit in animals.

References and Suggested Reading Buffington T, Holloway C, Abood A: Nutritional assessment. In Buffington T, Holloway C, Abood S, editors: Manual of veterinary dietetics, St Louis, 2004, Saunders, p 1. Chan DL: Nutritional requirements of the critically ill patient, Clin Tech Small Anim Pract 19:1, 2004. Freeman LM, Chan DL: Total parenteral nutrition. In DiBartola SP, editor: Fluid, electrolyte, and acid-base disorders in small animal practice, ed 3, St. Louis, 2006, Saunders, p 584. Novak F et al: Glutamine supplementation in serious illness: a systematic review of the evidence, Crit Care Med 30:2022, 2002. Pyle SC, Marks SL, Kass PH: Evaluation of complications and prognostic factors associated with administration of total parenteral nutrition in cats: 75 cases (1994-2001), J Am Vet Med Assoc 255:242, 2004. Torre DM, deLaforcade AM, Chan DL: Incidence and significance of hyperglycemia in critically ill dogs, J Vet Intern Med 21:971, 2007. Van den Berghe G et al: Intensive insulin therapy in critically ill patients, N Engl J Med 345:1359, 2001. Walton RS, Wingfield WE, Ogilvie GK: Energy expenditure in 104 postoperative and traumatically injured dogs with indirect calorimetry, J Vet Emerg Crit Care 6:71, 1998.

C H A P T E R 

4

Antiplatelet and Anticoagulant Therapy Marilyn Dunn, Quebec, Canada Marjory B. Brooks, Ithaca, New York

T

 hrombosis is a major cause of mortality for humans with heart disease, cancer, and stroke—the three most common causes of death in developed countries. Hereditary defects of coagulation inhibitors, referred to as thrombophilias, further increase the burden of thrombus formation in humans. Aspirin, heparin, and warfarin have long been the mainstays of antithrombotic therapy in medicine. However, limitations in drug safety and efficacy have prompted the development of new antiplatelet and anticoagulant drugs to supplement or replace traditional drug regimens. Although hereditary thrombophilias have not been identified in dogs or cats, thrombosis is recognized as a common complication of many acquired diseases, including cardiac, endocrine, inflammatory, and neoplastic disorders. Advances in our understanding of pathologic thrombus formation and recent pharmacokinetic studies of antithrombotic drugs in dogs and cats hold promise for the development of effective thromboprophylactic regimens in small animal practice.

Pathogenesis of Thrombosis Normal hemostasis is maintained through an intricate balance between endogenous anticoagulants and procoagulants. The net effect is preservation of blood flow in the systemic vasculature with localized coagulation at sites of vessel injury. Perturbations in this balance can tip the scales to either excessive bleeding or widespread thrombus formation (hypercoagulability). The concept of Virchow’s triad (endothelial damage, alterations in blood flow, and hypercoagulability) refers to underlying factors that act singly or in concert to promote thrombus formation in various disease states. The primary disorder influences the site of thrombus formation (arterial or venous vasculature), the composition of the occluding thrombus, and the approach to antithrombotic therapy. The relative proportions of platelets and fibrin in the clot depend on the shear of the injured vessel. Arterial thrombi form under high shear forces and therefore tend to contain a large number of platelets held together by fibrin strands. Venous thrombi form under low shear forces and consist primarily of fibrin and red blood cells. Strategies to inhibit arterial thrombogenesis typically include the use of antiplatelet drugs, whereas anticoagulants are the mainstay of venous thromboprophylaxis. Ultimately clinical trials are required for optimization of drug dosages and drug combinations for specific thrombotic syndromes. 24

Diagnosis of Hypercoagulability Identification of hypercoagulability is a great challenge in veterinary medicine. Routine coagulation tests (prothrombin time [PT], partial thromboplastin time [PTT]) are designed to detect “hypocoagulability,” and assays that measure consumption of anticoagulant proteins and fibrinogen are generally insensitive indicators of subclinical thrombosis. Nevertheless, low plasma antithrombin (AT) activity and high fibrin degradation product, D-dimer, and fibrinogen levels provide laboratory evidence of hypercoagulability. In human studies platelet hyperaggregability and expression of platelet activation markers such as P-selectin have been observed in patients with thrombotic tendencies. Thromboelastography (TEG) is a technique that depicts global hemostasis, beginning with clot formation and ending with clot lysis. Characteristic changes in the TEG profile have been associated with hypercoagulability in people. Evaluation of platelet function and TEG has been done and may prove useful in veterinary practice to detect hypercoagulability and monitor antiplatelet and anticoagulant therapy.

Antiplatelet Drugs Antiplatelet agents act through inhibition of platelet activation pathways or interference with membrane receptors. The three classes of antiplatelet drugs in current use include nonsteroidal antiinflammatory drugs (NSAIDs) (cyclooxygenase inhibitors), thienopyridines (adenosine diphosphate [ADP] receptor antagonists), and glycoprotein (GP)IIb/IIIa blockers (fibrinogen receptor antagonists).

Nonsteroidal Antiinflammatory Drugs Aspirin is recommended as the first-line antiplatelet drug in human cardiac syndromes and is the most commonly used antiplatelet drug in veterinary medicine. Aspirin causes irreversible acetylation of the platelet cyclooxygenase active site, leading to decreased thromboxane A2 synthesis. The effects of aspirin are permanent and last for the life span of the platelet (7 to 10 days). In contrast, other NSAIDs compete with arachidonic acid binding to cyclooxygenase, thereby producing a reversible inhibition. Despite its widespread use, prospective studies confirming the clinical efficacy of aspirin in thrombosis prevention in dogs and cats are lacking. In a retrospective study of immune-mediated

hemolytic anemia (IMHA) in dogs, improved survival was attributed in part to low-dose (0.5 mg/kg PO) aspirin administration (Weinkle et al., 2005). A retrospective study of cats with arterial thromboembolism demonstrated no difference in survival for cats treated with low-dose aspirin (5 mg/cat PO every 72h) compared with standard-dose aspirin (≥40 mg/cat q24-72h) or warfarin (Smith et al., 2003). Cats receiving standarddose aspirin had a greater risk of gastrointestinal hemorrhage than those receiving the low dose. Given the retrospective nature of the study, it was not possible to determine whether aspirin prophylaxis could prevent initial thrombus formation.

Thienopyridines Thienopyridines irreversibly inhibit the binding of ADP to specific platelet ADP receptors (P2Y12). ADP receptor blockade impairs platelet release reaction and ADPmediated activation of GPIIb/IIIa, thereby reducing primary and secondary aggregation response. These drugs must be metabolized by hepatic cytochrome p450, with platelet inhibition occurring by 3 days after initiation of therapy. Clopidogrel (Plavix, Sanofi-Aventis) and ticlopidine (Ticlid, Novopharm) are the two available thienopyridines. These drugs have been evaluated in healthy cats. Ticlopidine effectively decreased platelet aggregation but was associated with unacceptable gastrointestinal side effects. Clopidogrel at dosages of 18.75 to 75 mg PO every 24 hours was well tolerated and resulted in significant antiplatelet effects (Hogan et al., 2004). An ongoing prospective study (FATCAT) comparing clopidogrel to aspirin may help define the more effective agent for secondary prevention of feline aortic thrombosis. Plavix has been used empirically in dogs at a dosage of 1 to 2 mg/kg daily.

Glycoprotein IIb/IIIa Antagonists Activation of GPIIb/IIIa is the final common pathway of platelet aggregation, regardless of the initiating stimulus. Therefore drugs capable of inhibiting fibrinogen binding to GPIIb/IIIa are potent antiplatelet agents. Three intravenous GPIIb/IIIa antagonist drugs have been developed for clinical use in humans: monoclonal antibodies that bind to the receptor (abciximab [ReoPro], Lilly), and competitive mimetics of fibrinogen (eptifibatide [Integrilin, Schering and tirofiban [Aggrastat], Merck). In a study of cats with induced arterial injury, abciximab combined with aspirin reduced thrombus formation compared with aspirin alone (Bright, Dowers, and Powers, 2003). Administration of eptifibatide to cats caused circulatory failure and death and therefore is contraindicated. Although dogs have been used in pharmacokinetic and pharmacologic studies of GPIIb/IIIa antagonists, clinical studies have not been performed.

Anticoagulants Anticoagulants inhibit the generation of fibrin but do not dissolve preexisting fibrin clots (only thrombolytics can do this). Anticoagulants are used for thromboprophylaxis

Chapter  4  Antiplatelet and Anticoagulant Therapy 25 in patients considered at risk for a first thrombotic event and to limit fibrin formation in patients with documented thromboembolic disease.

Warfarin Warfarin (Coumadin, DuPont) is a vitamin-K antagonist that alters the synthesis of vitamin K–dependent clotting proteins (factors II, VII, IX, and X) and the anticoagulants, proteins C and S. Warfarin interferes with hepatic reductase activity, leading to impaired posttranslational carboxylation. The resultant des-carboxy vitamin K–dependent clotting factors have greatly reduced or absent activity. The anticoagulant activity of warfarin is delayed (4 to 5 days) as the newly synthesized inactive clotting proteins gradually replace their functional counterparts. Rapid inhibition of proteins C and S results in a transient period of hypercoagulability in humans, but this phenomenon has not been documented in dogs or cats. Warfarin is administered orally at an initial dosage of 0.2 mg/kg PO every 12 hours in dogs and 0.1 to 0.2 mg/kg PO every 24 hours in cats (Smith et al., 2000). Close monitoring for dosage adjustment is essential because the anticoagulant effect of warfarin is highly variable from one patient to another. Therapy is monitored based on PT, with a target prolongation to 1.5 times baseline. Because of the variability in PT reagent sensitivity, the World Health Organization has recommended that the PT be expressed as a ratio (International Normalized Ratio [INR]). The INR formula incorporates a factor (ISI) specific to each thromboplastin reagent and is calculated as follows: INR = (patient PT/ control PT)ISI. An INR target range of 2 to 3 is considered optimal, without causing excessive bleeding, for most human thrombotic syndromes. INR or PT monitoring is recommended daily for the first week of warfarin therapy, twice weekly for 3 weeks, then once a week for 2 months, and then every 2 months. Dose adjustments should be based on the total weekly dosage. Warfarin is available in 1-mg tablets that should not be divided because of uneven drug distribution throughout the tablet. Since most cats will receive 0.25 to 0.5 mg of warfarin, accurate dosing requires drug compounding. The most common veterinary use for warfarin is thromboprophylaxis for cats with cardiac disease; however, frequent monitoring to ensure optimal dosing is difficult in this patient population. Despite close monitoring, bleeding complications may occur. In one study between 13% and 20% of cats suffered bleeding complications, and 13% of cats had a fatal hemorrhage (Harpster and Baty, 1995). Clients must be informed of the risk of warfarin-induced hemorrhage and the requirement for intensive monitoring before warfarin therapy is initiated.

Heparin Unfractionated heparin (UH) is a glycosaminoglycan consisting of alternating residues of D-glucosamine and uronic acid. It is a heterogeneous mixture of chains ranging in molecular weight from 5,000 to 30,000 daltons with a mean length of 50 saccharides. Approximately one third of UH molecules possess a pentasaccharide sequence that binds to AT and accelerates its interaction with activated factors IIa (thrombin), IXa, Xa, XIa, and XIIa.

fXa

P se ent qu as e n ac ce ch a

HEPARIN

e

Section  I  Critical Care

rid

26

AT

fXa

AT

AT

Thrombin AT Thrombin Ternary complex

Fig. 4-1  Heparin binds antithrombin through the high-affinity pentasaccharide sequence and inactivates factor Xa. Inactivation of

thrombin also occurs but necessitates an additional 13 saccharides. (Modified from Hirsh J, Levine MN: Low-molecular-weight heparin, Blood 79:1, 1992.)

Thrombin and factor Xa are most responsive to inhibition by AT. Thrombin inactivation requires formation of a ternary complex involving heparin, AT, and thrombin (Fig. 4-1). Heparin is an indirect anticoagulant, exerting most of its effect through potentiation of AT activity. The drug is administered either intravenously or subcutaneously since it is very poorly absorbed orally. Heparin has been the anticoagulant of choice for thromboprophylaxis and treatment of thrombosis in human and veterinary medicine. Despite its widespread use, UH has a complex pharmacokinetic profile that produces an unpredictable anticoagulant effect. UH binds to numerous plasma proteins (lipoproteins, von Willebrand’s factor, fibrinogen, acute-phase proteins, and AT) and to endothelial cells, macrophages, and platelets. Because of its extensive binding to macrophages and endothelial cells, low-dose subcutaneous UH has poor bioavailability. For treatment of thrombosis in humans, UH typically is initiated with a bolus dose of 60 to 80 units/kg, followed by infusion of 12 to 15 units/kg/hour. Heparin therapy is then monitored by measurement of the PTT, with dosage adjustment to prolong values to 1.5 to 2.5 times the control value. In addition to PTT, heparin dosage has recently been based on measurement of plasma factor Xa inhibition, to the target range of 0.35 to 0.7 U/ml. Unlike PTT, anti-Xa activity is also suitable for monitoring low–molecular weight heparin (LMWH) therapy. Empiric UH therapy in veterinary medicine varies widely, encompassing a subcutaneous dosage range of 50 to 500 units/kg every 6 to 12 hours. Pharmacokinetic studies in healthy dogs have shown that dosages of 250 to 500 units/kg will result in target-range anti-Xa activities; however, hematoma formation occurred in some

dogs treated with 500 units/kg SQ at 8-hour intervals (Mischke, Schuttert, and Grebe, 2001). Little clinical data regarding UH monitoring exist in the veterinary literature; however, preliminary reports in IMHA dogs indicate that relatively high dosages (>300 units/kg SQ q6h) will be required to attain target anti-Xa levels (Breuhl, Scott-Moncrieff, and Brooks, 2005).

Low–Molecular Weight Heparin LMWHs are produced by depolymerization of UH, yielding chains with a mean molecular weight of 5000 daltons and chain lengths of less than 18 saccharides. Like UH, LMWHs possess a pentasaccharide region that binds to AT and accelerates its inhibition of factor Xa. The majority of LMWH molecules are too short to form a ternary complex with thrombin and AT; therefore their ratio of factor Xa to factor IIa inhibitory activity is approximately 4:1. In comparison, UH has a ratio of anti-Xa to anti-IIa activity of 1:1 (Fig 4-2). LMWHs bind poorly to plasma proteins and cells and undergo first-order renal clearance. In humans the subcutaneous bioavailability of LMWHs approaches 100%, and their elimination half-life allows once- or twice-a-day administration with no need for individual patient monitoring to adjust dosage. Although UH and LMWH demonstrate similar efficacy in most human trials, LMWH is gradually replacing UH because of its more favorable pharmacokinetic properties. The pharmacokinetics of two LMWHs (dalteparin [Fragmin], Pfizer) and enoxaparin (Lovenox, SanofiAventis) have been investigated in healthy dogs and cats, using anti-Xa activity to monitor anticoagulant effect. In dogs dalteparin has a half-life of 123 minutes, a vol-

Chapter  4  Antiplatelet and Anticoagulant Therapy 27



LMWH

e

id

ar ch c a as e nt enc e u P q se

fXa

fXa AT

AT

AT

Fig. 4-2  LMWH binds antithrombin through the high-affinity pentasaccharide sequence and inactivates factor Xa. LMWH containing less than 18 saccharides cannot bind to thrombin. (Modified from Hirsh J, Levine MN: Low-molecular-weight heparin, Blood 79:1, 1992.)

ume of distribution of 50 to 70 ml/kg of body weight, and an absolute bioavailability of 104% when administered subcutaneously (Grebe et al., 2000). Enoxaparin given to dogs at 0.8 mg/kg every 6 hours produced sustained anti-Xa activity in the range of 0.5 to 2 U/ml (Lunsford et al., 2005). Dalteparin given to dogs at 150 U/kg every 8 hours resulted in anti-Xa activity in the range of 0.2 to 1 U/ml (Mischke et al., 2001). A number of other LMWHs have been used experimentally in dogs (tinzaparin, nadroparin) and appear to have pharmacokinetic properties similar to those in people. In contrast, pharmacokinetic studies of dalteparin and enoxaparin in healthy cats revealed rapid absorption and elimination of the drugs, with peak effects 2 to 3 hours after drug administration. The predicted dosages required to maintain anti-Xa activity equal to or greater than 0.5 U/ml were 150 units/kg every 4 hours for dalteparin and 1.5 mg/kg every 6 hours for enoxaparin (Alwood et al., 2007). Although anti-Xa activity values are useful for defining UH and LMWH pharmacokinetics and comparing different dosage regimens in clinical trials, the in vivo anticoagulant effects of heparin are complex and not limited solely to factor Xa inhibition. A meta-analysis of human trials found that once-daily dosing of LMWHs was as effective in thromboprevention as 12-hour ­dosing (Dolovich et al., 2000), although once-daily dosing resulted in 12- to 14-hour periods with a subtherapeutic (defined as 15 minutes). Fluid Therapy Although there is little evidence supporting intravenous fluid therapy during cardiopulmonary arrest, it has long been advocated as a standard practice in veterinary CPCR. Although high fluid rates are appropriate for animals with preexisting hypovolemia or significant ongoing losses, experimental studies indicate that volume loading of euvolemic patients my actually cause a decrease in myocardial and cerebral perfusion. These findings have prompted investigation into small-volume resuscitation protocols using colloidal solutions and hypertonic saline. Although there is not enough evidence to make a standard recommendation, small-volume resuscitation using hypertonic saline may have a positive effect on resuscitation success and recovery after cardiopulmonary arrest.

Cpcr Monitoring Once CPCR has been instituted, it becomes necessary to evaluate the effectiveness of the procedure. ECG monitors should be attached to all CPCR patients. Unfortunately reading the ECG requires cessation of chest compressions and therefore has an adverse effect on ROSC. To minimize

the interruption of chest compressions, additional methods of monitoring are recommended. Clinicians frequently try to palpate arterial pulses during chest compression. Unfortunately retrograde blood flow into the venous system may produce femoral vein pulsations. Thus generation of a palpable pulse is not a reliable indicator of adequate compression and is not indicative of effective arterial flow. Doppler ultrasonography may be used to assess blood flow, but it is frequently affected by movement artifact. Although assessment of coronary artery perfusion might be helpful, it is technically difficult to measure and not routinely available. During cardiopulmonary arrest pulse oximetry will not function because pulsatile blood flow is inadequate in peripheral tissue beds. Arterial blood gas monitoring enables estimation of the degree of hypoxemia and the adequacy of ventilation during CPCR but is not a reliable indicator of the extent of tissue acidosis. In low-flow states such as cardiopulmonary arrest venous blood gas measurements are more reflective of intracellular events in the peripheral tissue beds than are arterial measurements. ETCO2 monitoring is a safe and effective noninvasive indicator of cardiac output during CPCR. The ETCO2 reading can be useful in monitoring the progression of CPCR because ETCO2 is linearly related to stroke volume when ventilation is controlled. In low-flow states many of the alveoli are not perfused; thus carbon dioxide (CO2) is unable to diffuse from the bloodstream into expired gas, and ETCO2 measurements are low. As blood flow improves, more alveoli are perfused, and more CO2 is excreted. Success of CPCR has been correlated with higher ETCO2 values in human and porcine models.

References and Suggested Reading 2005 American Heart Association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care, Circulation 112(24 suppl):IV1, 2005. Alzaga-Fernandez AG, Varon J: Open-chest cardiopulmonary resuscitation: past, present and future, Resuscitation 64:149, 2005. Cole SG, Otto CM, Hughes D: Cardiopulmonary cerebral resuscitation in small animals—a clinical practice review (part I), J Vet Emerg Care 12(4):261, 2002. Cole SG, Otto CM, Hughes D: Cardiopulmonary cerebral resuscitation in small animals—a clinical practice review (part II), J Vet Emerg Care 13(1):13, 2003. Haldane S, Marks SL: Cardiopulmonary cerebral resuscitation: emergency drugs and postresuscitative care, Compend Cont Educ Pract Vet 26(10):791, 2004. Haldane S, Marks SL: Cardiopulmonary cerebral resuscitation: techniques, Compend Cont Educ Pract Vet 26(10):780, 2004. Holowaychuk MK, Martin LG: Misconceptions about emergency and critical care: cardiopulmonary cerebral resuscitation, fluid therapy, shock, and trauma, Compend Cont Educ Pract Vet 28(6):420, 2006. Rieser TM: Cardiopulmonary resuscitation, Clin Tech Small Anim Pract 15(2):76, 2000. Varon J, Marik PE, Fromm RE: Cardiopulmonary resuscitation: a review for clinicians, Resuscitation 36:133, 1998. Waldrop JE et al: Causes of cardiopulmonary arrest, resuscitation management, and functional outcome in dogs and cats surviving cardiopulmonary arrest, J Vet Emerg Care 14(1):22, 2004.

C H A P T E R 

6

Traumatic Brain Injury Daniel J. Fletcher, Ithaca, New York Curtis W. Dewey, Ithaca, New York

T

rauma is a common presenting complaint in small animal veterinary emergency services, and traumatic brain injury (TBI) occurs in a high proportion of these animals. Common causes of TBI in dogs and cats include motor vehicle accidents, animal interactions, falls from heights, blunt trauma, gunshot wounds, and other malicious human behaviors. A global view of the patient is critical when treating TBI, and both extracranial and intracranial priorities must be addressed. Life-threatening extracranial issues such as penetrating thoracic and abdominal wounds or airway obstruction, as well as compromise of oxygenation, ventilation, or volume status must be identified and treated appropriately. Once extracranial factors have been addressed, the focus shifts to intracranial priorities such as maintenance of adequate cerebral perfusion pressure (CPP), oxygen delivery to the brain, and treatment of acute intracranial hypertension.

Pathophysiology The pathophysiology of head trauma can be separated into two categories: primary injury and secondary injury. Primary injury is the immediate result of the traumatic event, whereas secondary injury is comprised of a cascade of physiologic and biochemical events that occur in the subsequent hours to days.

Primary Injury The major types of primary injury that occur after head trauma include concussion, cerebral contusion, cerebral laceration, intraaxial and extraaxial hematomas, and skull fractures. Concussion is characterized by a brief loss of consciousness and is not associated with underlying histopathologic lesions. Hemorrhage into the brain parenchyma and secondary edema comprises cerebral contusion, which can lead to variable severity of clinical signs. Although mild contusion can be difficult to differentiate from concussion, unconsciousness for more than several minutes is most consistent with contusion. Laceration is characterized by physical disruption of the brain parenchyma and can lead to intraaxial hematomas within the brain parenchyma, as well as extraaxial hematomas in the subarachnoid, subdural, and epidural spaces. These space-occupying lesions cause compression of the brain, leading to severe localizing neurologic signs or diffuse dysfunction.

Secondary Injury TBI triggers a series of events that result in perpetuation of neuronal tissue damage, with both systemic

and intracranial insults occurring independently and in combination. Systemic perfusion derangements contributing to secondary brain injury include hypotension and hypoxemia. Disorders of ventilation contribute to secondary brain injury as well, with hypoventilation causing increased cerebral blood volume (CBV) and hypoxemia, and hyperventilation leading to cerebral vasoconstriction and reduced perfusion. Metabolic abnormalities such as hyperglycemia, hypoglycemia, electrolyte imbalances, and acid-base disturbances further perpetuate secondary brain injury. Intracranial insults include increased intracranial pressure (ICP), compromise of the blood-brain barrier (BBB), mass lesions, cerebral edema, infection, vasospasm, and seizures. All of these factors ultimately lead to neuronal cell death. Neuronal tissue is especially sensitive to oxidative damage because of its high lipid content. Many mechanisms favor production of reactive oxygen species after TBI, including local hemorrhage, catecholamine production, perfusion deficits, and local acidosis. Local biochemical processes in hypoperfused tissues lead to a milieu primed for generation of reactive oxygen species. Once perfusion is reestablished, these oxidized lipids, proteins, and deoxyribonucleic acids, result in further destruction of neurons. Damaged neurons inappropriately release excitatory neurotransmitters, causing sodium and calcium influx and depolarization and increasing cellular metabolic activity, depleting adenosine triphosphate stores. Nitric oxide (NO) has been associated with secondary brain injury after trauma, likely because of vasodilatory effects and production of free radicals. Production of other inflammatory mediators has been associated with TBI, leading to secondary injury, including BBB disruption, induction of NO production, mononuclear and polymorphonuclear cell chemotaxis, and activation of the arachidonic acid cascade.

Compromise of Cerebral Perfusion CPP is the net driving pressure leading to blood flow to the brain. It is defined as the difference between systemic mean arterial pressure (MAP) and ICP. CPP = MAP − ICP  Primary and secondary brain injuries leading to increases in ICP, in combination with systemic sequelae of the trauma such as hypovolemia leading to decreases in MAP, ultimately result in worsening of cerebral injury as a result of decreased CPP. Blood flow to the brain per unit time (cerebral blood flow [CBF]) is a function of CPP and cerebrovascular resistance (CVR). Autoregulatory mechanisms, dependent 33

34

Section  I  Critical Care

largely on local alterations in CVR, allow the normal brain to maintain a constant CBF over a wide range of MAP (50 mm Hg to 150 mm Hg). These autoregulatory mechanisms are commonly compromised in patients with TBI, making them more susceptible to ischemic injury with decreases in MAP. Acute increases in ICP often trigger the “Cushing’s reflex,” a characteristic combination of systemic hypertension and sinus bradycardia. The initial drop in CPP resulting from increased ICP leads to a dramatic increase of sympathetic tone, causing systemic vasoconstriction and increased cardiac output, ultimately leading to significant increases in MAP. Stimulation of baroreceptors in the aorta and carotid sinus by the increase in MAP triggers a reflex sinus bradycardia. The presence of the Cushing’s reflex in a patient with head trauma is a sign of a potentially life-threatening increase in ICP and should be treated promptly.

Assessment, Diagnostics, and Monitoring Neurologic Assessment The modified Glasgow Coma Scale (MGCS) score is a ­quantitative measure that has been shown to be associated with survival to 48 hours in dogs with TBI and provides a score that can be used to assess both initial neurologic status and progression of signs (Platt, Radaelli, and McDonnell, 2001). This scale incorporates three domains: level of consciousness, posture, and pupillary size/response to light, with a score of 1 to 6 assigned to each domain. The final score ranges from 3 to 18, with lower scores indicating more severe neurologic deficits. The initial neurologic examination should be interpreted in light of the cardiovascular and respiratory systems since shock can have a significant effect on neurologic status.

Initial Diagnostics Because of the likelihood of multisystemic injury associated with head trauma, initial diagnostics and patient monitoring should focus on a global assessment of patient stability. An initial emergency database should consist of a packed cell volume and total solids to assess for hemorrhage; blood glucose to assess severity of injury; and a blood gas (venous or arterial) to assess perfusion, ventilation, oxygenation, and acid-base status. If possible, samples for a complete blood count and blood chemistry should be obtained before therapy to assess renal and hepatic function and to screen for other systemic disease. In general, occlusion of the jugular vein is contraindicated in patients with TBI because this can lead to increased ICP caused by decreased venous outflow from the brain; therefore samples should be obtained peripherally or via peripherally inserted central catheters. Imaging of the head is indicated in patients with localizing signs of brain dysfunction, those with moderate-to-severe neurologic deficits that do not respond to aggressive extracranial and intracranial stabilization, and those with progressive neurologic signs. These studies can yield information about targets of potential surgical

intervention such as intraaxial or extraaxial hemorrhage, skull fractures, or cerebrospinal fluid leaks. Skull radiographs have low sensitivity in the assessment of patients with TBI and rarely yield useful diagnostic information. Computed tomography is a sensitive imaging modality that yields excellent detail for assessment of skull fracture, acute hemorrhage, and brain edema.

Monitoring The overall duration and frequency of episodes of hypoperfusion and tissue oxygenation deficits have been associated with poorer outcomes in people with TBI. Therefore serial monitoring of these parameters is essential for successful management of these patients. Frequent qualitative assessment of tissue perfusion via mucous membrane color; capillary refill time; heart rate and pulse quality; and quantitative assessment of blood pressure, oxygenation, and ventilation is crucial. A minimal MAP of 80 mm Hg should be targeted to decrease the risk of inadequate CPP. If the Doppler technique is used for monitoring, a minimum systolic pressure of 100 mm Hg should be the target. Continuous electrocardiograph monitoring should also be used if possible; if episodes of sinus bradycardia are noted, blood pressure should be assessed for evidence of the Cushing’s reflex, which warrants aggressive therapy directed at lowering ICP. Techniques have been described for continuous or intermittent direct monitoring of ICP. These techniques are invasive and can lead to complications but yield valuable information for the management of patients with TBI and allow calculation of CPP, the most important of the parameters determining CBF. General guidelines are to maintain ICP below 20 mm Hg and to maintain a CPP of at least 60 mm Hg.

Treatment Treatment priorities for patients with TBI can be divided into two broad categories: extracranial and intracranial. Successful management of patients with TBI depends on addressing both categories.

Extracranial Priorities Because of the high likelihood of multisystem trauma in patients with TBI, assessment of potential extracranial injuries is an essential part of the initial diagnostic workup. As with any severely injured patient, the basics of Airway, Breathing, and Circulation (i.e., the ABCs) should be evaluated and addressed as necessary. Airway patency should be assessed as soon as possible. Endotracheal intubation or tracheostomy should be considered if complete or partial obstruction is present. Even mild hypercapnia can significantly increase ICP and should not be tolerated. Conversely, hyperventilation leading to hypocapnia can cause cerebral vasoconstriction, decreasing CBF and leading to cerebral ischemia. Therefore manual or mechanical ventilation should be used if necessary to maintain CO2 at the low end of the normal range (i.e., venous PCO2, 40 to 45 mm Hg; arterial PCO2, 35 to 40 mm Hg). The pharynx and larynx should be suctioned as needed to maintain airway patency.

Chapter  6  Traumatic Brain Injury 35

Because hypoxia is common in patients with traumatic injury, supplemental oxygen is indicated in the initial management of all patients with TBI. Patients with pulmonary contusions or other pulmonary parenchymal disease may require mechanical ventilation with positive end-expiratory pressure to maintain adequate oxygenation. Patients with TBI commonly present in hypovolemic shock, and volume resuscitation goals should be aggressive (MAP of 80 to 100 mm Hg). For patients without electrolyte disturbances normal saline (0.9%) is the best choice of the isotonic crystalloids since it contains the smallest amount of free water and is least likely to contribute to cerebral edema. Synthetic colloids can have a more rapid and longlasting effect in hydrated patients but are not effective in dehydrated patients. Patients with hypotension caused by hypovolemia and concurrent increased ICP will benefit from a combination of a synthetic colloid (see Chapter 11) (hetastarch or dextran 70) and hyperosmotic (hypertonic saline [HTS]) solution. See Table 6-1 for recommended doses. Patients who do not respond to volume resuscitation require vasopressor support. Because CPP is dependent on MAP, systemic hypotension must not be tolerated.

Intracranial Priorities The main goals of intracranial stabilization are maintaining adequate cerebral perfusion by controlling ICP, reducing cerebral metabolism, and maintaining adequate systemic blood pressure.

Hyperosmotic Agents Mannitol is an effective therapy for patients with increased ICP and has been shown to reduce cerebral edema, increase CPP and CBF, and improve neurologic outcome in TBI. It has a rapid onset of action, with clinical improvement occurring within minutes of administration, and these effects can last as long as 1.5 to 6 hours. Mannitol boluses of 0.5 to 1.5 g/kg have been recommended for treatment of increased ICP in dogs and cats. High-dose mannitol boluses (1.4 g/kg versus 0.7 g/kg) were shown to result in improved neurologic outcome in humans in a recent clinical trial (Cruz et al., 2004). Mannitol may increase the permeability of the BBB, an effect that is most pronounced when the BBB is exposed to the drug for prolonged periods of time. The increased permeability can allow mannitol to leak into the brain parenchyma, where it can exacerbate edema. To reduce the risk of this effect, the drug should be administered in repeated boluses rather than as a continuous-rate infusion. The diuretic effect of mannitol can be profound and can cause severe volume depletion. Therefore treatment must be followed with isotonic crystalloid solutions and/or colloids to maintain intravascular volume. In humans mannitol may induce acute renal failure if serum osmolarity exceeds 320 mOsm/L; therefore, if possible, serum osmolality should be measured when repeated doses are administered. HTS is a hyperosmotic solution that may be used as an alternative to mannitol in patients with head injury. Because sodium does not freely cross the intact BBB, HTS

Table  6-1 Drugs and Doses for Patients With Traumatic Brain Injury Indication

Drug

Dose

Comments

Intracranial Hypertension Euvolemic, normotensive, or hypertensive patients

Mannitol 25%

0.5-1.5 g/kg IV over 15 minutes; may repeat

Hypovolemic patients

HTS (7%)* + dextran-70 or hetastarch

3-5 ml/kg over 15 minutes; may repeat

Hypovolemic or euvolemic patients

HTS (7-7.8%)

3-5 ml/kg over 15 minutes; may repeat

Potent osmotic diuretic. Follow with crystalloids and/or colloids to maintain intravascular volume. Monitor osmolality with repeat dosing. Contraindicated in hyponatremic patients. Monitor serum sodium concentrations with repeat dosing. Contraindicated in hyponatremic patients. Monitor serum sodium concentrations with repeat dosing. If using 23.4% solution, dilute 1 part HTS with 2 parts 0.9% saline or sterile water.

Diazepam or midazolam

0.5 mg/kg IV or rectal bolus; may repeat; 0.2-0.5 mg/kg/hr IV CRI 16 mg/kg loading dose (divided into 4 doses q2-4h); 2 mg/kg q12h maintenance dosage 120 mg/kg/day PO for 5 days, then 30 mg/kg/day PO

Anticonvulsant Therapy Actively seizing patients

Prophylaxis for immediate or Phenobarbital early seizures, status epilepticus, or cluster seizures Potassium bromide

CRI, Continuous-rate infusion; HTS, hypertonic saline; IV, intravenously. *23.4% HTS: dilute 1 part HTS with 2 parts dextran-70 or hetastarch. 7% to 7.5% HTS: administer separate doses of HTS and dextran-70 or hetastarch (3-5 ml/kg each).

Do not administer diazepam CRI into peripheral catheters because of the risk of phlebitis. Evaluate chemistry for evidence of hepatic dysfunction. Monitor ventilation and blood pressure during loading. Sodium bromide can be substituted at the same dose and given IV.

36

Section  I  Critical Care

has osmotic effects similar to those of mannitol. Other beneficial effects of HTS include improved hemodynamic status via volume expansion and positive inotropic effects, as well as beneficial vasoregulatory and immunomodulatory effects (Ware et al., 2005). Rebound hypotension is uncommon with HTS administration because, unlike mannitol, sodium is actively resorbed in the kidneys, especially in hypovolemic patients. This makes it preferable to mannitol for treating patients with increased ICP and systemic hypotension caused by hypovolemia. Combining HTS with a synthetic colloid can prolong this volume expansion effect (see Table 6-1). HTS is contraindicated in patients with hyponatremia because it can cause rapid rises in serum sodium concentrations, leading to central pontine myelinolysis and delayed neurologic signs. In euvolemic patients with evidence of intracranial hypertension, both mannitol and HTS can have beneficial effects. If an individual patient is not responding to one drug, the other may yield a beneficial response. Corticosteroids Corticosteroids are potent antiinflammatory medications and have been recommended in human and veterinary medicine to treat TBI. A recent clinical trial evaluating over 10,000 human adults with head injury showed that treatment with corticosteroids was associated with worse outcome at 2 weeks and 6 months after injury (Edwards et al., 2005). Because of the lack of evidence of any beneficial effect of corticosteroids after TBI and strong evidence from the human literature showing a detrimental effect on neurologic outcome, corticosteroids should not be administered to dogs and cats with TBI. Furosemide Furosemide has been used to treat cerebral edema either as a sole agent or in combination with mannitol. This use has been called into question because of the potential for intravascular volume depletion and systemic hypotension, ultimately leading to decreased CPP (Chesnut et al., 1998). It should be reserved for patients in whom it is indicated for other reasons such as those with pulmonary edema or oligoanuric renal failure. Decreasing Cerebral Blood Volume Cerebral vasodilation and blood pooling can cause increases in the total volume of blood within the calvaria or in the CBV and can contribute to increased ICP. Several techniques to decrease CBV have been described and have been shown to be effective in people with increased ICP. Hypercapnia caused by hypoventilation can cause cerebral vasodilation and increased CBV. Ventilatory support should be targeted at maintenance of normocapnia (arterial CO2 of 35 to 40 mm Hg). In cases of severe, acute intracranial hypertension, short-term hyperventilation to an arterial CO2 of 25 to 35 mm Hg may be used to reduce CBV and ICP. However, chronic hyperventilation is not recommended because the decrease in CBF can lead to cerebral ischemia. Elevation of the head by 15 to 30 degrees reduces CBV by increasing venous drainage, decreasing ICP, and increasing CPP without deleterious changes in cerebral

oxygenation (Ng and Wong, 2004). It is imperative that occlusion of the jugular veins be avoided by using a slant board to prevent bending the neck. Angles greater than 30 degrees may cause a detrimental decrease in CPP. Anticonvulsant Therapy Seizures are common after TBI in humans, with reported incidence rates of up to 54% (Frey, 2003). Posttraumatic seizures are divided into three groups: immediate, occurring within 24 hours of the trauma; early, occurring 24 hours to 7 days after trauma; and late, occurring longer than 7 days after trauma. Several controlled clinical trials have been undertaken in human medicine to investigate the efficacy of prophylactic anticonvulsant therapy after TBI, and a meta-analysis showed an overall reduction in the risk of immediate and early seizures with prophylactic anticonvulsant therapy (Schierhout and Roberts, 1998). Given these data, short-term prophylactic therapy for 7 days after trauma may be indicated in patients with TBI, and anticonvulsant therapy should always be instituted for patients with TBI who develop immediate or early seizures, but there is little evidence to support the use of long-term anticonvulsant therapy to prevent late seizures in these patients. Suggested traditional anticonvulsant drugs and doses are listed in Table 6-1. In addition, several newer anticonvulsant medications have become available in recent years (see Chapter 232). These may prove to be useful alternatives by allowing more thorough neurologic evaluation than traditional anticonvulsants, which have significant sedative effects. Control of Hyperglycemia Presence and persistence of hyperglycemia have been associated with worse outcome in numerous clinical studies in human children and adults with TBI. Only one retrospective veterinary study has evaluated the association between hyperglycemia and TBI; and, although an association between admission hyperglycemia and severity of neurologic injury was noted, there was no association between hyperglycemia at admission and survival (Syring, Otto, and Drobatz, 2001). A recent small trial comparing 14 humans with TBI treated with intensive insulin therapy to maintain strict control of blood glucose levels to 33 humans treated with a less strict protocol found significantly lower brain glucose levels in the intensive therapy group but no significant difference in neurologic outcome between the groups (Vespa et al., 2006). This is an active area of research, but, until larger outcome studies are available, there is little evidence to support the use of insulin therapy in patients with TBI. Decreasing Cerebral Metabolic Rate TBI can lead to increased cerebral metabolic rate (CMR) and can result in cerebral ischemia and cellular swelling. Therefore therapies targeted at decreasing CMR can reduce secondary brain injury. Induction of barbiturate coma and hypothermia have been used in experimental studies and clinical trials in humans to reduce CMR. Barbiturate coma can effectively decrease ICP via reductions in CMR and has been shown to improve outcome in humans with refractory intracranial hypertension, but hypothermia has not been associated with improved outcome and is not recommended.

Decompressive Craniectomy Several surgical procedures to address increased ICP have been described in human medicine, including CSF drainage and decompressive craniectomy. The goal of these therapies is to allow expansion of the various intracranial compartments without a subsequent increase in ICP. The use of decompressive craniectomy in human patients with TBI is controversial, and a large-scale, randomized human clinical trial is currently underway (the RESCUEicp Trial), which will compare aggressive medical management with decompressive craniectomy in 500 patients with TBI (Hutchinson et al., 2006). Pending results of this trial, we recommend adoption of current recommendations in the human literature; consider decompressive craniectomy within 12 hours in patients with sustained, increasing ICP that is refractory to medical therapy.

Prognosis Prognosis following TBI is difficult to predict, and only the MGCS has been shown to be correlated with outcome in small animal patients (Platt et al., 2001). However, our clinical experience would suggest that even patients with severe neurologic deficits at presentation can show marked improvement over the subsequent 24 to 48 hours. Therefore serial neurologic examinations are recommended. Client education is also of paramount importance since persistent or permanent neurologic deficits in patients with TBI are common.

Chapter  6  Traumatic Brain Injury 37

References and Suggested Reading Chesnut RM et al: Neurogenic hypotension in patients with severe head injuries, J Trauma 44:958, 1998. Cruz J et al: Successful use of the new high-dose mannitol treatment in patients with Glasgow Coma Scale scores of 3 and bilateral abnormal pupillary widening: a randomized trial, J Neurosurg 100:376, 2004. Edwards P et al: Final results of MRC CRASH, a randomised placebo-controlled trial of intravenous corticosteroid in adults with head injury-outcomes at 6 months, Lancet 365:1957, 2005. Frey LC: Epidemiology of posttraumatic epilepsy: a critical review, Epilepsia 10(suppl):11, 2003. Hutchinson PJ et al: Decompressive craniectomy in traumatic brain injury: the randomized multicenter RESCUEicp study (www.RESCUEicp.com), Acta Neurochir 96(suppl):17, 2006. Ng I, Lim J, Wong HB: Effects of head posture on cerebral hemodynamics: its influences on intracranial pressure, cerebral perfusion pressure, and cerebral oxygenation, Neurosurgery 54:593, 2004. Platt SR, Radaelli ST, McDonnell JJ: The prognostic value of the modified Glasgow Coma Scale in head trauma in dogs, J Vet Intern Med 15:581, 2001. Schierhout G, Roberts I: Prophylactic antiepileptic agents after head injury: a systematic review. J Neurol Neurosurg Psychiatry 64:108, 1998. Syring RS, Otto CM, Drobatz KJ: Hyperglycemia in dogs and cats with head trauma: 122 cases (1997-1999), J Am Vet Med Assoc 218:1124, 2001. Vespa P et al: Intensive insulin therapy reduces microdialysis glucose values without altering glucose utilization or improving the lactate/pyruvate ratio after traumatic brain injury, Crit Care Med 34:850, 2006. Ware ML et al: Effects of 23.4% sodium chloride solution in reducing intracranial pressure in patients with traumatic brain injury: a preliminary study, Neurosurgery 57:727, 2005.

C h apter  

7

Vascular Access Techniques James S. Wohl, Auburn, Alabama Marion B. Tefend, Auburn, Alabama

P

ercutaneous placement of intravascular catheters is the most common method of achieving access to the vasculature for fluid therapy, frequent blood collection, and physiologic monitoring. In emergency patients large-bore peripheral catheters typically are indicated for rapid fluid resuscitation, but they can be problematic because of hypotension, hypovolemia, vascular collapse, trauma, and skin stiffness. Central line catheters are indicated in all severely hypovolemic patients or if central venous pressure monitoring or serial blood sampling is indicated. In some instances emergency venous or arterial access requires a cutdown procedure. Knowledge of reliable anatomic landmarks and proper surgical technique facilitate successful placement of vascular catheters in the critically ill patient. Cutdowns help ensure that the vessel is cannulated on the first attempt and can allow placement of a larger catheter than what can normally be placed percutaneously. Intraosseous access can be used for all small patients, as well as small birds and reptiles. Intraosseous cannulation (Bonagura, 1992) provides a route for fluid and drug administration but is inadequate for blood collection and cardiovascular monitoring. Percutaneous placement of arterial catheters (Bonagura, 1995) is indicated in patients requiring repeated arterial blood gas analysis or direct arterial blood pressure measurement.

Catheter Selection Access to the vasculature in the critically ill or traumatized patient allows for the delivery of lifesaving medications, fluid therapy, blood products, or nutrition, all of which can be accomplished through a wide range of specialty catheters. Proper nursing care to patients harboring such devices is critical because any indwelling catheter or tube represents a focus for microbial colonization. Incorrect placement or positioning can cause patient discomfort or compromise. Appropriate selection as to the catheter or tube type, in combination with proper management techniques, is paramount to patient care. Recognizing the advantages and disadvantages of the different types of specialty tubes and the care necessary for maintaining patency of such tubes will benefit patient outcome and prevent unnecessary complications. Peripheral venous catheters such as the over-the-needle type are the most commonly used method of obtaining vascular access in the small animal patient. Advantages of this catheter type include ease and speed of insertion, low cost, and versatility of access in different anatomic locations. Flow rates are greatly enhanced by placement of 38

short (2-inch) large-bore (12 to 16 g) catheters placed intravenously. Anatomic location for the peripheral catheter is best used in the cephalic, accessory cephalic, or jugular vein during triage. Other sites of placement of the peripheral over-the-needle catheter can include the saphenous or medial saphenous vein, dorsal common digital vein, or articular or lingual vein. Other uses of the over-theneedle catheter type include pericardiocentesis, abdominocentesis, or thoracocentesis. Another advantage of the over-the-needle catheter is the variety of both the gauge and length available to the practitioner, ranging from 25 g to 12 g and from 2 inches up to 12 inches in length. Central venous access catheters are advantageous for monitoring central venous pressure, obtaining serial blood sampling with minimal stress to the patient, longterm patient use, and administrating of hyperosmolar solutions. The central venous catheter is most commonly placed in the jugular vein but can be readily inserted into the caudal vena cava via the lateral or medial saphenous veins. Other advantages of the central venous catheter are the wide variety of styles available to the veterinarian. Some central venous catheters contain multiple lumens for the simultaneous delivery of incompatible fluid types. Such multilumen catheters are also advantageous to the critical patient in need of fluid therapy, central venous pressure monitoring, intravenous (IV) nutrition, or continuous-rate infusions of medications, all of which can be done through one catheter. Disadvantages of the central venous catheter include a longer placement time, expense, slight patient discomfort during placement, and the relatively narrow diameter of the catheter itself. Since most central venous catheters are long and narrow, rapid fluid administration is not recommended as the primary delivery route, particularly during resuscitation. In addition, since most central venous catheters are placed into a jugular vein, patients with coagulation deficiencies may have complications with association of such devices. Monitoring for extravasations in the central venous catheter is a little more difficult than in the peripheral overthe-needle catheter. Caregivers should monitor the patient for edema of the neck, shoulder, or face; pain with insertion of medication; sluggish flow through the catheter; or inability to aspirate blood back from the catheter. Long over-the-needle types of central venous catheters are inexpensive and come in a variety of lengths and diameters, ranging from 22 to 16 gauge and from 6 to 12 inches in length. Disadvantages of these catheter types include patient discomfort since they tend to be stiff and are prone to kinking. In addition, most over-the-needle long catheters are made of Vialon or

Teflon material, and should be changed after 5 to 7 days. Central venous catheters placed by the Seldinger technique include the single-to-multilumen devices, which are soft and flexible, made of an antithrombogenic polyurethane material, and can be maintained for longer periods. In addition, some Seldinger central venous catheters are impregnated with antimicrobial solutions that may result in a reduction of catheter-related sepsis. Disadvantages to the Seldinger central venous catheter types are expense, increased risk of local hemorrhage during insertion, and procedure time needed for placement. However, it is our opinion that the advantages of such central venous catheters far outweigh the risks and expense in critical patient use. Arterial catheters provide an important means by which to monitor a patient’s status. Inserted primarily into the dorsal pedal artery, catheterization can also be accomplished in the femoral, brachial, or even the auricular artery. Advantages to arterial catheterization include monitoring patient ventilation, acid-base equilibrium, and direct blood pressure monitoring. Over-the-needle peripheral catheters can be used for such procedures, although arterial catheter kits are now available using the Seldinger technique for ease of placement and long-term use. Percutaneous arterial catheterization is technically difficult because arteries are surrounded by a dense adventitia, are located deeper in fascial tissues than veins, and are not visible through the skin. Arterial catheterization can be further complicated by hypotension or hypovolemia. Medications should not be administered through arterial catheters. Vascular access ports, or implantable vascular access systems, are subcutaneous delivery systems that allow serial blood sampling or IV administration of medications or fluid. Such devices are advantageous to chronically ill patients that can be treated intermittently on an outpatient basis. Surgically implanted, the catheter and port are subdermal and can be accessed without patient discomfort. Complications associated with such systems are similar to those of other types of IV catheters, including topical infection, sepsis, thrombosis, or extravasations. Nursing care required for vascular ports include daily insertion site inspection, mild antiseptic cleansing, and intermittent heparinized flushes to prevent clogging or occlusion.

Catheter Placement Techniques Seldinger Technique Catheters using the Seldinger technique can be placed percutaneously or following exposure of the vessel after mini cutdown or cutdown. Commercially available in single-, double-, or triple- lumen (Arrow, Cook, BeckonDickinson, Baxter, or Abbott catheter systems), sizes range from 22 to 16 gauge for peripheral use to 14 gauge to 24 gauge for central use. Lengths range from 16 to 30 cm. Most central catheters are made of polyurethane to help prevent thrombosis and can also be purchased with silver sulfadiazine and chlorhexidine (Arrow International) heparin coating. See Box 7-1 for venous access procedure and Box 7-2 for arterial access procedure.

Chapter  7  Vascular Access Techniques 39

Box  7-1 Venous Access Procedure   1. Place patient in sternal recumbency with neck hyperextended.   2. Shave a wide area to avoid contamination of insertion site.   3. Perform surgical preparation with solutions containing povidine and isopropyl alcohol.   4. Apply sterile drape to area cranial to insertion site.   5. Premeasure guidewire; tip of guidewire should not exceed apex of heart.   6. Premeasure central catheter length; tip of catheter should be located in cranial vena cava just outside of the right atrium for central venous pressure monitoring.   7. Place large-bore, short cephalic catheter.   8. Insert straight end of wire into the vessel via the cephalic catheter to predetermined length.   9. Remove cephalic catheter; ensure that the wire does not inadvertently back out. 10. Insert the plastic dilator into the vessel by placing the wire through it and guiding it to the vessel. Passage of dilator may be facilitated by “tenting” the skin and gently rotating the dilator into the vessel; a cut into the skin with a No. 11 blade next to the wire may ease insertion. Insert one-half length of dilator into the vessel; then remove the dilator. 11. Insert the catheter over the wire and guide it into the vessel to predetermined length. Ensure that the end of the wire is projecting out the distal end of the catheter before advancement; the wire should be held as the catheter is advanced into the vessel. If double-lumen catheters are used, the wire should come out the distal (or colored) port. 12. Remove the wire, leaving the catheter in place 13. Aspirate catheter with small syringe; blood should easily flow into syringe. Flush the catheter with sterile saline and cap. 14. Secure the catheter in place with skin/fascia sutures, apply antiseptic/antibiotic ointment, and place under a sterile dressing. If entire length of catheter is not used, secure excess catheter with plastic catheter holders provided.

Venous Cutdown Techniques Patient Preparation Except in the most emergent situations, aseptic technique should be maintained during catheter placement. Clipping and surgical preparation of the skin 180 degrees around the cutdown site allow aseptic handling of a limb. Infusion of lidocaine into the skin and subcutis of the proposed cutdown site facilitates placement in awake or sedated patients. Final preparation includes a last surgical scrub and the maintenance of a sterile field containing the necessary instruments, catheters, syringes filled with heparinized saline, injection plugs, stopcocks, and fluid tubing. Sterile latex gloves should be worn when attempting invasive vascular access techniques. Since the focus of the surgeon is on the cutdown site, it is essential that nongloved assistants be present to monitor the patient’s vital signs during the procedure.

40

Section  I  Critical Care

Box  7-2 Arterial Access Procedure Materials Needed • Clippers • Surgical scrub • Suture material • Heparinized saline flush • Catheter cap • Arterial catheter kit or cephalic catheter • Bandage material • Saline for infusion if continuous direct blood pressure monitoring is used Procedure   1. Lay patient in lateral recumbency.   2. Give oxygen if body position compromises respiratory effort.   3. Clip and prep dorsal pedal area (down leg).   4. Palpate pulse with single digit.   5. Stab incision for cutdown at 45-degree angle and at least 1 inch away from palpable pulse.   6. Hold catheter like a dart; insert catheter with bevel up through tunneled area.   7. Insert catheter gently toward pulse (superficial); back out and redirect if no flash.   8. Once flash is obtained, be careful not to move catheter; slide entire length of wire via black tab-handle.   9. “Pop” catheter off the wire and into arterial space. 10. Remove wire and ensure blood flow (should be fast and in spurting or jet motion). 11. Cap and flush catheter; aspirate back to ensure blood flow and reflush. 12. Suture in place (three spots total). 13. Place small amount antibiotic cream over insertion site. 14. Cover with sterile gauze square. 15. Place one layer gauze bandage. 16. Cover catheter with light, stiff bandage and label catheter.

cutdown incisions should be made in the middle-tocranial portion of the jugular groove. The maxillary vein is a branch of the external jugular vein and is located half the distance between the wing of the atlas and the mandibular salivary gland. For cephalic and lateral saphenous vein cutdowns, incisions are made over their expected locations on the dorsal antebrachium and lateral aspect of the distal tibia, respectively. The surgical technique is similar for all venous sites. A scalpel blade is used to incise the skin directly over or adjacent to the vein. Either a transverse or a parallel skin incision can be made. Care should be taken to incise only the full thickness of the skin. Blunt dissection (e.g., with mosquito forceps) may be required to visualize the vein as a blue-topurple tubular structure within the subcutaneous tissue. Minimal dissection is usually required for the placement of an over-the-needle or through-the-needle catheter. In some instances it may be necessary to isolate the vein. Isolation is accomplished by blunt dissection parallel to the vein. Subcutaneous or adventitial tissue adjacent to the vein is retracted with atraumatic thumb forceps, exposing the vessel. Dissection with the use of sharp-ended scissors is then performed dorsally and ventrally to the vein. Dissecting in a parallel fashion minimizes the chances of rupturing or traumatizing the vessel. After freeing the vein from the subcutaneous tissue, a hemostat is advanced beneath the vein. A silk suture is then clasped by the hemostat and drawn beneath the vessel (Fig. 7-1). The vein can be briefly occluded proximally to enhance filling. The suture can then be used to retract the vein distally and provide adequate tension for the catheterization of the vessel (Fig. 7-2). Alternatively, the vessel may be sacrificed by ligating the vein distally and using the ligature to retract the vessel.

Mini Cutdown The mini cutdown technique is used for gaining access to the cephalic and lateral saphenous veins. With the bevel facing the operator, a sterile 20- or 22-gauge hypodermic needle is scraped across the skin directly over and parallel to the underlying vein in a proximal-to-distal direction. Tearing skin in this fashion releases skin tension without damaging the underlying vessel. Alternatively a small incision can be made over the vein with a scalpel blade. Although an incision causes a less traumatic defect to the skin, care must be taken to avoid incising the vessel and subcutaneous tissue. A mini cutdown can be used to visualize a collapsed vein but is more commonly used to avoid tissue drag during catheter placement. This technique is most useful in cats with thick skin or when burring of an over-the-needle catheter is prohibiting percutaneous placement. Infusion of lidocaine before mini cutdown is rarely needed, especially in very sick patients. Surgical Cutdown Surgical cutdowns can be used over the external jugular, maxillary, cephalic, or lateral saphenous vein. If attempting catheterization of the external jugular vein,

Fig. 7-1  Following isolation of the blood vessel, a hemo-

stat is used to pass a silk suture beneath the vessel. (Art by Lisa Makarchuk; courtesy Auburn University, School of Veterinary Medicine, Auburn, Alabama.)



Fig. 7-2  Retraction of the vessel with a suture applies tension to the vessel, allowing introduction of an over-the-needle catheter. (Art by Lisa Makarchuk; courtesy Auburn University, School of Veterinary Medicine, Auburn, Alabama.) A second suture is placed beneath the vessel proximally. The vein is then cannulated through a venotomy (or by venipuncture) between the two ligatures. Following catheterization, the proximal suture is ligated, securing the catheter in the vein.

Arterial Cutdown Techniques The most common site for arterial catheterization is the dorsal metatarsal artery. This artery is most superficial in the proximal metatarsus, medial to the extensor tendons, between the second and third metatarsal bones. A second arterial site is the dorsal pedal artery, which courses medial to the long digital extensor tendon at the level of the proximal tarsus. The femoral artery is less commonly used because of its location and the risk of hemorrhage, the potential danger of puncturing the external iliac artery, and retroperitoneal bleeding. When a surgical cutdown is performed for arterial catheterization, a technique should be used that preserves vascular sufficiency. An incision is made over the pulsation of the dorsal metatarsal artery in the proximal metatarsus. When isolating the dorsal pedal artery, the incision is made medial and parallel to the long digital extensor in the proximal tarsus. Dissection is performed parallel to the direction of the artery, as described earlier for isolating a vein. The artery is identified as a white tubular structure. A pulse may be palpated, which will distinguish the artery from a nerve or tendon. A silk suture is placed beneath the artery and retracted distally to expose and place tension on the vessel. An over-the-needle catheter, primed with heparinized saline, is recommended for arterial cannulation. Through-the-needle catheters have a smaller diameter

Chapter  7  Vascular Access Techniques 41 than the penetrating needle and puncture wound; consequently, leakage of blood can result at the catheter insertion site. A more expensive alternative to an overthe-needle catheter is to use the modified Seldinger technique. This method uses a guidewire over which the catheter is advanced into the artery. A vessel dilator is sometimes used before introducing the catheter. Although the Seldinger technique is thought to be the least traumatic method of catheter placement, arterial cannulation usually can be achieved with over-theneedle catheters. Topical administration of a few drops of 2% lidocaine onto the artery may prevent arterial spasm and facilitate cannulation. Retracting the artery with silk suture, the needle catheter assembly is inserted into the artery until rapid flow of red arterial blood fills the needle hub. The assembly is then repositioned in line with the artery and advanced an additional few millimeters. The catheter is then advanced off the needle and into the artery. The needle is discarded, and a sterile Luer-Lok injection plug is attached to the catheter. The catheter is flushed with a small volume of heparinized saline. Aspiration of arterial blood through the plugged catheter with a needle and syringe confirms the appropriate placement within the artery. It is important to keep the artery retracted during this procedure to prevent slippage of the artery off the unsecured catheter. In anesthetized patients venous blood may be superoxygenated and have the appearance of arterial blood. Observing pulsatile, rapid blood flow through the open catheter before the insertion of an injection cap indicates that the cannulated vessel is an artery. Blood gas analysis revealing an oxygen tension compatible with arterial blood or connection to a pressure-monitoring ­ system will further confirm proper placement.

Securing the Catheter Without Sacrificing the Artery The silk retraction suture is removed from beneath the artery. A silk suture with a swaged-on needle is placed above the artery but beneath the hub of the catheter. A finger trap suture is tied around the catheter hub, leaving excess suture on both ends of the second knot. The catheter is allowed to lie in a stationary position, and the remaining length of suture is used to anchor the catheter through the skin, placing minimal tension on the catheter. This method secures the catheter in place without sacrificing the artery and allows withdrawal of the catheter after cutting the anchoring skin suture. One or two interrupted skin sutures may be required proximal to the anchor suture to close the incision site. Following suturing of the catheter and the incision site, a sterile dressing is applied, and the catheter is bandaged routinely. In awake patients, a soft, padded bandage can be used to inhibit movement of the tarsus. Patency of the catheter is maintained by periodic flushing with small volumes (1 to 2 ml) of heparinized saline injected through the injection cap with a 25-gauge needle or a low-dose saline continuous-rate infusion from a pressurized fluid bag if the catheter is used for continuous blood

42

Section  I  Critical Care

pressure monitoring. Manual flushing of larger volumes of fluid with a syringe can cause retrograde blood flow and embolization of particulate matter or air. Most transducer systems used for direct blood pressure monitoring use a squeeze clamp or pigtail flushing device. Attaching a multiport stopcock to the catheter allows connections to a blood pressure monitor and a flushing system and provides an additional site for blood collection. When not in use, stopcock ports should be attached to sterile ­injection plugs.

Blood Collection With the stopcock to the designated collection port turned off, the sterile injection plug is removed and protected from contamination by placing it on a sterile gauze square or other sterile field. A sterile 3-ml syringe containing 1 ml of heparinized saline is then attached to the collection port. The stopcock to the flushing system is turned off, and 1 ml of blood is drawn through the catheter into the flush syringe. The stopcock to the patient is turned off, and the sample port and the flush syringe are discarded. The flushed blood mixture should not be reinfused following arterial blood collection. A new sterile syringe that has been purged with heparin (if obtaining a blood gas sample) is then attached, the stopcock closed to the flushing system, and the desired amount of blood is drawn slowly into the syringe. Rapid, forced withdrawal may injure the artery. After sample collection the stopcock is closed to the sample port, the sample syringe is removed, and the system is flushed for 1 second via the flushing system. To minimize thrombus formation and bacterial contamination, the sample stopcock should be flushed following blood collection. This is achieved by turning the stopcock to the patient off and allowing irrigation solution to flow through the open sample port. Sterile gauze can be used to collect the expelled solution. Following this procedure, the sterile injection plug is returned to the sample port.

Complications and Removal of Arterial Catheters An arterial catheter should be removed as soon as it is no longer essential for proper patient management. In humans arterial catheters are associated with a higher rate of thrombus formation after a 3- or 4-day dwell time. Evidence of vasculitis, skin discoloration, hemorrhage, or an unexplained fever should prompt evaluation of the catheter site. Cooler-than-normal skin temperature distal to the catheter insertion site may indicate developing catheter-related insufficiency in blood supply and impending ischemic necrosis. Administration of medications through the arterial catheter is not recommended. When an arterial catheter is removed, all bandage and dressing material should be removed. The anchoring suture is then cut. Firm pressure is applied proximal and distal to the insertion site while the catheter is removed with mild continuous suction applied by a syringe. This method facilitates aspiration of clots surrounding and within the catheter. On catheter removal firm manual pressure is applied over the insertion site for 5 to 10 minutes. After

the application of manual pressure, a pressure dressing is applied for several hours. The insertion site is monitored periodically for internal or external hemorrhage.

Maintenance of Venous and Arterial Catheters Any indwelling venous or arterial catheter predisposes a patient to the possibility of nosocomial infection. All personnel involved with placing the catheter or monitoring the patient must be aware of such risk and use caution when changing bandages, administering fluids or medications, withdrawing blood, or manipulating three-way stopcocks on monitoring devices attached to the catheter. Infection will occur as a result of contaminated IV solutions, failure to maintain a strict protocol for skin preparation, poor insertion technique, failure to clean equipment between patients, or failure to routinely change the catheter bandage. Insertion sites should be monitored routinely for thrombosis, patient discomfort, catheter migration, and extravasation. Phlebitis is a commonly encountered complication of indwelling vascular catheterization. Phlebitis can occur as a result of inflammation associated with movement of a stiff catheter in a vein or artery or from bacterial infection that can lead to sepsis. Aseptic technique should be used whenever possible to minimize infection. Catheters should also be routinely changed according to type (e.g., changing over-the-needle peripheral catheters every 72 hours and long over-the-needle central catheters every 120 hours into new anatomic site). Minimizing tape use and anchoring with suture to secure catheters aid in insertion site inspection and patient comfort. Polyurethane Seldinger-type central catheters (Arrow International) may stay in for the length of patient hospitalization but still need daily insertion site cleaning, inspection for signs of thrombosis or leakage, and daily bandage changes. Bacterial contamination of catheter sites can result from caregiver handling, heparinized flush syringes, blood left inside an injection port, and even tops of medication bottles. Caregivers should practice proper hygiene protocols, including washing hands frequently, swabbing ports and medication bottles with antiseptics, and frequently changing bandages to any catheter in any anatomic location. Flush solution should also be changed every 48 hours to avoid microbial contamination. Sterile technique and catheter care should be maintained for any type of fluid administration. However, nursing management of catheters used for parenteral nutrition warrants special focus because nutritional formulas are excellent mediums for bacterial colonization. Catheter care includes strict sterile technique during insertion, including proper skin preparation, placement of a sterile underwrap over insertion site, and strict aseptic technique in care of IV tubing and administration bags. The IV lines should not be disconnected; if diagnostic testing or frequent walking is necessary, the IV lines and administration bags should accompany the patient. Intravenous injections should follow sterilization of the port. If a multilumen catheter is placed, proper identification to each port is necessary, with one line dedicated to the total parenteral nutrition solution only (usually the proximal port).



Chapter  8  Pacing in the Critical Care Setting 43

Catheter Care

Jugular catheter care also requires daily inspection as indicated previously. The insertion site should be cleaned with povidone solution and/or alcohol. Since the jugular catheter is significantly longer in length than the cephalic catheter, signs of extravasation may not be as apparent. The midsternal region should be examined for edema related to jugular venous catheter placement, and the proximal aspect of the medial hind limb should be examined for edema related to lateral or medial saphenous venous catheter placement. Bandaging material needed includes a 4×4 gauze pad with antibiotic ointment, followed by a single layer of casting padding, followed by Kling gauze and vet wrap. No tape is necessary to anchor a jugular catheter if it has been sutured in place. Note that neck bandages should have the “twofinger rule” (i.e., the bandage should be loose enough to slide two fingers under for patient comfort). If the jugular catheter is made of polyurethane material (i.e., Arrow International), it does not need to be changed out within a 90-day period. Other catheter types made from polypropylene material (MILA, Intracath) can be changed on the fifth day.

Arterial and cephalic catheter care should be performed every 24 hours. All supportive bandages should be removed, and the insertion site inspected for signs of phlebitis or thrombosis (i.e., redness, swelling, or ropelike vein). The catheter should be flushed with a small amount of heparinized saline (1 to 2 ml) using a pulsing movement while palpating tip of catheter. If any swelling or pain results from the flush, the catheter should be removed. If the patient is not on IV fluids, the catheter should be flushed every 4 hours (cephalic or jugular). Arterial catheters used for blood pressure monitoring should be flushed with heparinized saline every 2 hours or alternatively attached to a pressurized continuous-rate infusion which will maintain patency. When using the latter approach, it is important to maintain sufficient pressure in the cuff surrounding the fluid bag. If the catheter is patent, the area should be cleaned with dilute povidone scrub or alcohol wipe and then dried. A small amount of povidone or antibiotic ointment can be placed over the insertion site before rebandaging the catheter. Recommended bandaging material is 2-inch tape (one piece to secure the catheter, and one piece to anchor a T-port, if used), cast padding in a single layer, followed by Kling gauze and vet wrap for the final layer. The date of placement of the catheter should be recorded, as well as the date of the rewrap. Catheters should be checked routinely every 2 hours for leakage or swelling. Swelling distal to the catheter usually indicates a tight bandage. Swelling proximal to the catheter could indicate extravasation of the administering fluid or medication.

C h apter  

References and Suggested Reading Bonagura JD, editor: Kirk’s current veterinary therapy XI (small animal practice), Philadelphia, 1992, Saunders, p 107. Bonagura JD, editor: Kirk’s current veterinary therapy XII (small animal practice), Philadelphia, 1995, Saunders, p 110.

8

Pacing in the Critical Care Setting Anna R.M. Gelzer, Ithaca, New York Marc S. Kraus, Ithaca, New York

T

emporary cardiac pacing is a potentially lifesaving procedure for patients with severe bradyarrhythmias or those that are at a high risk of asystole in the emergency setting. Temporary cardiac pacing depends on rate support from an external pulse generator via electrodes that can be placed in a timely fashion and removed easily after a short period of pacing. Most situations requiring temporary pacing in veterinary medicine necessitate permanent pacing therapy, which will need to be initiated before removal of the temporary system (see Chapter 160).

This chapter focuses on two commonly used techniques in veterinary medicine: transcutaneous external pacing (DiFrancesco et al., 2003) and transvenous external pacing, procedures for which there are a number of clinical indications (Box 8-1). Transesophageal pacing may be used for atrial pacing, but ventricular capture is inconsistent. Because it has limited applicability to the veterinary critical care setting, it will not be discussed further. Once the decision is made to support the heart rate by external pacing, pharmacologic interventions aimed at

44

Section  I  Critical Care

Box  8-1  Indications for Temporary Pacing in the Critical Care Setting • Asystole during cardiopulmonary arrest • High grade second- or third-degree atrioventricular (AV) block with slow ventricular escape rhythm and secondary hemodynamic compromise or syncope • Symptomatic sick sinus syndrome: frequent episodes of sinus arrest resulting in syncope • Sinus bradycardia or second-degree AV block with hypotension not responsive to atropine or isoproterenol • Ventricular tachyarrhythmias secondary to bradycardia • Overdrive suppression of tachyarrhythmias • Causes of transient medically refractory sinus bradycardia or AV block resulting in hemodynamic instability (i.e., drug toxicities): • Calcium channel blockers • β-Blocker • Digoxin

rate support (anticholinergics, sympathomimetics) should be discontinued. These drugs tend to be proarrhythmic and can sensitize the myocardium to stimulation from catheter manipulations, causing ventricular arrhythmias.

External transcutaneous temporary pacing External transcutaneous pacing (TCP) generators come as stand-alone units or incorporated into a defibrillator. Both Zoll Medical Corp., Chelmsford, MA (M SERIES models) and Medtronic Inc., Minneapolis, MN (Lifepak models) feature user-friendly pacemaker/defibrillator units. Pacing can be achieved rapidly with very limited training and without a need to move a patient to fluoroscopy. However, TCP creates significant skin and muscle pain, necessitating general anesthesia for the duration of temporary pacing.

Materials and Technique Required for Transcutaneous Pacing The materials required to provide TCP include airway and anesthetic equipment and the external pacing unit with two sets of electrodes. Electrocardiograph (ECG) electrodes are used for rhythm monitoring, and larger pacing electrode pads for cardiac stimulation. (Lifepak, Medtronic and Zoll Medical provide proprietary pads, but other companies also offer pacing pads that can be used with adaptors.) Pacing electrode pads come in pediatric and adult sizes. Pediatric pads should be used for animals less than 10 kg. If the animal is conscious but hemodynamically unstable because of a bradyarrhythmia, the TCP should be planned by first establishing intravenous access and ensuring that airway management can be provided once the patient is anesthetized. The animal’s chest needs to be clipped over at least as large an area as the pacing pads will cover. The pads are placed over the right and left precordia. The caudal edge of the pad should be

positioned where the apex beat is felt strongest under the operator’s hand; this “sandwiches” the heart between the pads. The ECG lead cables of the pacing unit need to be attached for the pacing system to monitor the inherent heart rhythm properly, including sensing of native electrical activity. While most units will also record the ECG from the thoracic electrode patches, rhythm monitoring during external pacing is best done from standard limb leads to reduce the confusion of local twitch artifact. It is important to place the ECG electrodes as far away from the pacing pads as possible to obtain a clear ECG signal on the pacing unit monitor. Set the pacing rate at 60 to 90 beats/min. The target heart rate is selected to maintain cardiac output and improve the blood pressure. For hemodynamically compromising bradycardia without cardiac arrest, start the pacing output at 0 mA, and increase the output by 10 mA until capture is achieved. In the asystole cardiac arrest setting, start at the maximum current setting and decrease the output to a value above where capture is lost. To achieve external pacing capture, a relatively high current output is required in dogs. Less than 70 or 80 mA does not usually result in successful capture, and most cases appear to require equal to or higher than 90 mA. The ECG generated by TCP should only be interpreted on the pacing unit monitor. A built-in filter and blanking protection change the high-output pacing stimulus to a smaller spike, preventing distortion of the ECG waveform. In contrast, regular ECG systems may display a huge pacing spike with no clearly identifiable ECG. In addition, chest thumping produced by TCP contributes to the artifactual appearance of the recordings from a regular ECG machine. To assess capture, look at the ECG tracing on the monitor for pacer spikes that are followed by both a QRS complex and a distinct T-wave. Electrical capture is manifest as a wide QRS complex, with a prominent T wave with opposite polarity of the QRS complex (Fig. 8-1). Both electrical and mechanical capture must be achieved to ensure cardiac output. Mechanical capture is only evidenced by a concurrent pulse (Fig. 8-2). Arterial pressure can be monitored with a direct arterial line, a Doppler sphygmomanometer system, or an oxygen saturation monitor displaying a pulse waveform. In the emergency setting palpation of a femoral pulse may be used. Skeletal muscle contractions occur with pacemaker current output as low as 10 mA and are not an indicator of electrical or mechanical capture. These become more intense as the current output is increased. TCP is likely the least invasive and quickest means to achieve rate support in the course of cardiopulmonary resuscitation (CPR). It is safe to touch the patient or the pacing patches and perform CPR while TCP is ongoing. Since the patient is already unconscious, considerations regarding anesthesia for TCP are not applicable at that instant. However, it should be remembered that, if successful pacing is instituted, patients that were unconscious at the outset may regain consciousness, in which case general anesthesia must be readily available. If surgery for a permanent pacemaker therapy is required following institution of TCP, it may be necessary to paralyze the animal during part of the surgery. The muscle stimulation of TCP can create so much body motion that surgical exposure of the jugular vein for

Chapter  8  Pacing in the Critical Care Setting 45



very effective but requires manual or mechanical ventilation because of paralysis of the diaphragm. If a permanent pacemaker is placed during TCP, one should be aware that the pacing stimulus is sensed as a far-field signal by the permanent pacemaker (if it is programmed VVI or demand-mode) even at currents as low as 1 mA. This means that the permanent pacemaker is inhibited to pace, even after the output of the transcutaneous pacer is reduced to loose capture. Blood pressure monitoring will reveal loss of pacing instantly. To avoid this, the heart rate of the transcutaneous pacer should be set lower than the permanent pacemaker so as to not inhibit pacing.

A

Transvenous temporary pacing Transvenous pacing (TVP) is effective, comfortable once in place for the awake patient, and fairly stable if correctly positioned. Therefore it is the treatment of choice for prolonged temporary pacing. Several companies provide external-demand pacing units. Medtronic (model 5348) and Oscor Inc. (model Pace 101H) both feature user-friendly, stand-alone, and economical external pacers. Several types of catheters can be used for TVP. We use regular bipolar pacing catheters (No. 4 or 5 Fr) that can be connected directly to the external pacing generator. Alternatively, easy-to-advance balloon-tipped pacing leads are available (Balloon Flotation Bipolar Pacing Catheter, Arrow International Inc.).

B Fig. 8-1  A, ECG tracing of transcutaneous pacer unit with noncapture; the trace shows intermittent electrical capture. Arrows indicate paced beats. However, the second and fourth pacing stimuli do not result in capture (no QRS following the spike). The current output is set too low (60 mA) and should be increased. B, ECG tracing of transcutaneous pacer unit with capture. The trace shows continuous electrical capture. Each pacing spike is followed by a QRS complex. The current output was increased to 90 mA.

Sedation for Placement of Transvenous Pacing Catheter

Blood pressure

ECG

Transvenous pacing is most commonly used to bridge the time until permanent pacemaker implantation can be

Blood pressure

ECG

permanent pacemaker placement is impaired. In our experience large-breed dogs do not exhibit excessive twitching, but small-breed dogs and cats demonstrate significant whole-body thumping. To reduce muscle contractions, neuromuscular blockade with atracuronium (0.1 to 0.2 mg/kg intravenously [IV] for 20 minutes’ duration) is

A

B

Fig. 8-2  A, Transthoracic pacing at 60 mA with no capture. Note that the surface ECG recorded with a regular physiorecorder shows large pacing spikes, obscuring the inherent ECG of the dog. Interpretation of the ECG alone would lead one to believe that there is adequate pacing. However, the blood pressure tracing reveals a discrepancy of heart rate between the ECG trace and the pressure trace because of lack of electrical and mechanical capture. The blood pressure trace shows the rate of the ventricular escape rhythm, displaying an irregular slow pulse. B, Transthoracic pacing at 90 mA with capture. Note that the surface ECG looks very similar to the example in panel A. The small positive deflection after the large pacing spike represents the QRS complex of electrical capture. However, only the concurrent blood pressure tracing confirms definitively that both electrical and mechanical capture is achieved.

46

Section  I  Critical Care

performed. Since general anesthesia usually exacerbates bradyarrhythmias, the temporary pacing should be instituted before induction of general anesthesia. Light-toheavy sedation and local anesthesia are usually required to insert the introducer sheath percutaneously. A combination of a sedative with a pain-relieving drug and an immobilizing agent is very effective. We like to use midazolam (0.3 to 0.5 mg/kg IV) with fentanyl (3 mcg/kg IV) and ketamine (1 to 2 mg/kg IV). If the animal needs to be even quieter, propofol (1 mg/kg IV) can be added. At the site of catheter insertion a local lidocaine block (2%, 0.5 ml SQ) should be infused to reduce pain. This protocol provides 10 to 20 minutes of sedation. The introducer sheath (No. 5 Fr, 6Fr, or 7 Fr Critical Care Arrow-Flex Polyurethane Sheath with Integral Hemostasis Valve/Side Port, Arrow International) is placed percutaneously using the modified Seldinger technique.

Placement of Transvenous Pacing Catheter The proper choice of the insertion site is essential for success. If the temporary pacing lead is placed only to bridge a short time frame until permanent pacemaker surgery can be performed, we prefer to gain access via the femoral vein for TVP. This allows for a clean approach later to at least one or possibly both external jugular veins for the permanent pacing lead. However, if temporary pacing needs to last for several hours in the intensive care unit, the groin is not an optimal site for access. In an awake or only mildly sedated animal movement of the rear limb may displace the introducer sheath enough to pull out the pacing lead or result in local hemorrhage. If longerterm pacing is anticipated, a technically easier approach is cannulation of the external jugular vein. The right jugular vein is the shortest and most direct route, providing the most stable lead position. The introducer sheath can be secured safely to the skin and is subject to little movement if the neck is properly wrapped. The lateral saphenous vein may also be used for percutaneous access; however, we found that this approach can be impeded by the long distance and indirect route (i.e. navigating the catheter past the stifle joint is difficult because of the bend). Except for sick sinus syndrome, in which right atrial pacing will suffice, most conditions requiring emergency pacing involve advanced atrioventricular (AV) block or

I P II

III

II P III

asystole, requiring ventricular pacing. Blind advancement of temporary pacing leads from the introducer sheath to the right ventricular apex is challenging. Monitoring the ECG for signs of capture of the pacing spike may be helpful, but frequently blind advancement results in catheter malposition. The catheter could enter the internal thoracic vein, the azygos vein, or the caudal vena cava or potentially curl up in the right ventricle. As a consequence of curling, pacing capture is poor or intermittent as a result of improper contact of the lead tip with the endomyocardial surface. Some balloon-tipped pacing catheters feature a lumen for pressure monitoring, which is helpful for blind placement. However, in our experience by far the fastest method is to use fluoroscopic guidance. Optimally a pacing catheter is placed with fluoroscopic guidance. For ease of handling, we only connect to the external pacer once the lead is positioned properly in the right ventricular apex. However, if the lead has to be advanced blindly, it must be connected to the external pacer during the placement to use the continuous ECG for guidance. A small pacing spike can be visualized once the wire tip is near the heart, and capture of the atrial myocardium (P wave) may occur while the catheter is advanced toward the tricuspid valve. The pacing spike will be followed by a wide QRS complex once ventricular capture is established (Fig. 8-3). In a true emergency situation such as during CPR, pacing has to be achieved without fluoroscopy. Since blind transvenous placement is almost impossible during chest compression, it may become inevitable to proceed to open-chest resuscitation to provide external rate support. In such instances the tip of the pacing lead can be held directly on the epicardial surface of the heart to achieve capture until the patient is stabilized, and fluoroscopic imaging can be used to place a lead transvenously.

External pacer programming The external pacer should be set on demand-pacing, or VVI, mode. This means that it will pace the ventricle when needed but also sense the patient’s intrinsic ventricular activity, which inhibits the pacer. This avoids stimulation during the vulnerable period (T wave) of the intrinsic beats to prevent induction of ventricular arrhythmias. The heart rate should be set to the minimum rate to achieve an adequate blood pressure. It is not advised to pace much faster

Pacing spike P Paced QRS

aVR

Fig. 8-3  Transvenous pacing. Surface ECG of a dog with third-degree atrioventricular block. The

patient is being instrumented with a transvenous pacing catheter. After a long episode of asystole, a bipolar pacing spike is visualized, followed by a wide QRS complex, indicating successful ventricular capture.



Chapter  8  Pacing in the Critical Care Setting 47

than 80 to 90 beats/min unless absolutely necessary. In the case of sudden loss of capture, long episodes of sinus arrest may ensue as a result of overdrive suppression of the escape focus (the length of the pause is positively correlated to the preceding pacing rate). Typically ventricular capture by endocardial pacing can be achieved using between 1 to 5 V. Many temporary pacemakers do not indicate voltage but instead milliamperes of current output. If pacing resistance is low, capture is often obtained between 2 and 5 mA. The current threshold to achieve capture should be determined for each patient individually by gradually decreasing the voltage until loss of capture occurs. Twice threshold provides an adequate margin of safety. If the paced heart rate is less than the set rate, possible causes include: (1) poor lead position, (2) insufficient pacing voltage/current, (3) competing native rhythm (sinus capture, premature beats), and (4) T-wave sensing. T-wave sensing can be unmasked by briefly moving the selector switch to the full VOO (asynchronous) mode. If the paced rate is now correct, T-wave sensing is likely.

the introducer sheath should be aseptically covered inside the neck wrap. Since the temporary pacing leads have a smooth profile with no fixation mechanism, spontaneous displacement is likely. We suture a clip right outside the introducer sheet, which fits tight around the catheter and seems to fix it in place fairly well. The external pacing unit needs to be attached securely to the patient to avoid accidental traction on the pacing lead, and the generator batteries should be checked regularly. If ventricular ­capture becomes intermittent or requires greater than 5 V, lead displacement may have occurred, and a chest x-ray is indicated.

Monitoring of prolonged temporary transvenous pacing Temporary TVP can be maintained for several days in an awake animal. Medically refractory drug toxicities such as overdose with a calcium channel blocker is an indication for longer-term temporary pacing. Aseptic technique during placement of the introducer sheath and pacing lead is imperative, and antibiotic coverage is recommended to prevent infection. The part of the lead extruding from

References and Suggested Reading Bocka JJ: External pacemakers, accessed 11/2005 from http://www. emedicine.com/emerg/topic699.htm. Bocka JJ: External transcutaneous pacemakers, Ann Emerg Med 18:1280, 1989. DeFrancesco TC, et al: Noninvasive transthoracic temporary cardiac pacing in dog, J Vet Intern Med 17:663, 2003. Fitzpatrick A, Sutton R: A guide to temporary pacing, Br Med J 304:365, 1992. Gammageer MD: Temporary cardiac pacing, Heart 83:715, 2000. Seldinger SI: Catheter replacement of the needle in percutaneous arteriography; a new technique, Acta Radiol 39:368, 1953. Trigano JA, Birkui PJ, Mugica J: Noninvasive transcutaneous cardiac pacing: modern instrumentation and new perspectives, PACE 15:1937, 1992. Zoll PM et al: External noninvasive temporary cardiac pacing: clinical trials, Circulation 71:937, 1985.

C h apter  

9

Fluid Therapy Stephen P. Dibartola, Columbus, Ohio Shane W. Bateman, Columbus, Ohio

F

luid therapy is supportive. The underlying disease process that caused the fluid, electrolyte, and acidbase disturbances must be diagnosed and treated appropriately. Normal homeostatic mechanisms allow considerable margin for error in fluid therapy, provided that the heart and kidneys are normal. This is fortunate because clinical estimation of dehydration may be quite inaccurate. Fluid therapy potentially consists of three phases: resuscitation, rehydration, and maintenance. Most patients in shock require rapid administration of a large volume of crystalloid or colloid to expand the intravascular space and correct perfusion deficits. Dehydrated patients require sustained administration of crystalloid fluids for 12 to 36 hours to replace fluid losses from interstitial and intracellular spaces. Normally hydrated patients unable to consume sufficient water require maintenance fluid therapy with crystalloid solutions. In formulating a fluid therapy plan, eight questions should be considered: 1. Is the patient suffering from a shock syndrome that requires immediate fluid administration? 2. Is the patient dehydrated? 3. Can the patient consume an adequate volume of water to sustain normal fluid balance? 4. What type of fluid should be given? 5. By what route should the fluid be given? 6. How rapidly should the fluid be given? 7. How much fluid should be given? 8. When should fluid therapy be discontinued?

Is the patient suffering from a shock syndrome that requires immediate fluid administration? Shock patients urgently require fluid therapy. The presence of altered mental status and cool extremities in association with tachycardia or severe bradycardia, mucous membrane pallor, prolonged or absent capillary refill time, reduced or absent peripheral pulses, and hypotension are among the most common physical examination findings in patients in shock. Such physical examination findings and a compatible clinical history are the basis for the decision to institute a resuscitation phase of fluid therapy. Hypovolemic and distributive shock states are most likely to respond to intravascular volume expansion. Obstructive forms of shock often respond favorably to moderate volume expansion. Fluid administration is contraindicated in patients with cardiogenic forms of shock. Regardless of their underlying disease, severely dehydrated patients can be in shock and require a resuscitation 48

phase of fluid therapy before initiating the rehydration phase. However, not all patients in shock are dehydrated, and some may not require a rehydration phase of therapy. The rapidity and volume of loss from both the intravascular and extravascular fluid compartments in conjunction with the extent of any compensatory response will determine whether the patient is in shock or is dehydrated.

Is the patient dehydrated? The need for a rehydration phase depends on the underlying condition of the patient and an assessment of the animal’s state of hydration. The hydration status of the animal is estimated by careful evaluation of the history, physical examination findings, and the results of a few simple laboratory tests. In its most narrow sense dehydration refers to loss of pure water. However, the term dehydration usually is used to include hypotonic, isotonic, and hypertonic fluid losses. The type of dehydration is classified by the tonicity of the fluid remaining in the body (e.g., a hypotonic loss would result in hypertonic dehydration). Isotonic and hypotonic losses are most common in small animal practice. Severe volume depletion can result in nonosmotic stimulation of antidiuretic hormone (ADH) release, thus preventing effective excretion of consumed water and contributing to hypotonic dehydration.

Fluid Balance Normally fluid input consists of water consumed in food, water that is drunk, and water produced metabolically in the body. Maintenance water and electrolyte needs parallel caloric expenditure; and normal daily losses of water and electrolytes include respiratory, fecal, and urinary losses. Respiratory loss of fluid can be important in dogs because panting has been adapted for thermoregulation in this species. Pyretic patients also can lose fluid by this route. Normally cutaneous losses are unimportant in dogs and cats because eccrine sweat glands are limited to the foot pads and do not play an important role in thermoregulation in these species. In disease states decreased fluid intake results from anorexia, and increased fluid loss may occur by urinary (e.g., polyuria) and gastrointestinal (e.g., vomiting, diarrhea) routes. Less common routes of loss include skin (e.g., extensive burns), respiratory tract, and salivary secretions. Third-space loss of fluid occurs when effective circulating volume is decreased but the fluid lost remains in the body. Examples include intestinal obstruction,

peritonitis, pancreatitis, and effusions or hemorrhage into body cavities. Decreased fluid intake and increased loss often coexist (e.g., anorexia, vomiting, and polyuria in a uremic animal).

History The history may suggest the affected fluid compartment or compartments, as well as the patient’s electrolyte and acid-base derangements. The time period over which fluid losses have occurred and an estimate of their magnitude should be determined. Information about food and water consumption, gastrointestinal losses (e.g., vomiting, diarrhea), urinary losses (i.e., polyuria), and traumatic losses (e.g., blood loss, extensive burns) should be obtained. Excessive insensible water losses (e.g., increased panting, pyrexia) and third-space losses may be determined from the history and physical examination. The clinician’s knowledge of the suspected disease can aid in predicting the composition of the fluid lost (e.g., vomiting caused by pyloric obstruction leads to loss of hydrogen, chloride, potassium, and sodium ions and development of metabolic alkalosis; small-bowel diarrhea typically leads to loss of bicarbonate, chloride, sodium, and potassium ions and development of metabolic acidosis).

Physical Examination Physical findings associated with fluid losses of 5% to 15% of body weight vary from no clinically detectable changes (5%) to signs of hypovolemic shock and impending death (15%). The hydration deficit is estimated by evaluating skin turgor, moistness of the mucous membranes, position of the eyes in their orbits, heart rate, character of peripheral pulses, capillary refill time, and extent of peripheral venous distention (i.e., inspection of jugular veins). A decrease in the interstitial compartment volume leads to decreased skin turgor and dryness of the mucous membranes. A decrease in plasma volume leads to tachycardia, alterations in peripheral pulses, and collapse of peripheral veins. When these cardiovascular signs are present, the patient is in shock and should be resuscitated promptly before correction of the hydration deficit. Typically such signs of hypovolemic shock appear with fluid loss that amounts to 10% to 12% of the patient’s body weight. The fluid deficit in a given patient is difficult to determine with accuracy because of the subjectivity of skin turgor evaluation and the possibility of undetected ongoing (contemporary) losses. When evaluated by skin turgor, obese animals may appear well hydrated as a result of excessive subcutaneous fat despite being dehydrated. Conversely, emaciated and older animals may appear more dehydrated than they actually are because of lack of subcutaneous fat and elastin. Thus a crude clinical estimate of hydration status and the patient’s response to fluid administration become important tools in evaluating the extent of dehydration and planning fluid therapy. The urinary bladder should be small in a dehydrated animal with normal renal function. In the absence of urinary obstruction, a large bladder in a severely dehydrated patient indicates failure of the normal renal concentrating mechanism.

Chapter  9  Fluid Therapy 49 Body weight recorded on a serial basis traditionally has been considered a good indicator of hydration status, especially when fluid loss has been acute and previous body weight has been recorded (i.e., 1-kg loss of body weight equals a 1-L fluid deficit). However, in one study clinician estimates of hydration in dogs and cats admitted to a veterinary teaching hospital intensive care unit did not reliably predict changes in weight after 24 to 48 hours of fluid therapy. In chronically ill animals loss of weight also includes loss of muscle mass. Anorexic animals have been estimated to lose 0.1 to 0.3 kg of body weight per day per 1000 kcal energy requirement. Losses in excess of this amount indicate fluid loss. Another factor that must be considered in evaluating body weight is the possibility of third-space loss. Fluid lost into a third space does not decrease body weight.

Laboratory Findings Packed cell volume (PCV), total plasma protein concentration (TPP), and urine specific gravity (USG) are simple laboratory tests that aid in the evaluation of hydration. These results should be obtained before initiating fluid therapy. PCV and TPP should be evaluated together to minimize errors in interpretation. PCV and TPP increase with all types of fluid losses excluding hemorrhage; whereas serum sodium concentration increases, decreases, or remains unchanged, depending on the type of loss (e.g., hypotonic, hypertonic, isotonic) and the presence or absence of nonosmotic stimulation of ADH release. The USG before fluid therapy is helpful in the preliminary evaluation of renal function. It should be high (>1.045) in a dehydrated dog or cat if renal function is normal. This may not be true if other disorders affecting renal concentrating ability such as medullary washout of solute are present. Furthermore, previous administration of corticosteroids or furosemide can decrease urinary concentrating ability.

Can the patient consume an adequate volume of water to sustain normal fluid balance? Volume-resuscitated and rehydrated patients may not have recovered sufficiently to eat and drink normally. Such patients require ongoing fluid therapy. Maintenance fluid requirements have been determined from studies of normal animals, and the needs of partially or completely anorexic dogs and cats are not well understood. Also, absorption and metabolism of nutrients produce solutes that must be excreted in urine. Sensible fluid losses and urine production are decreased during fasting in normal animals because less solute requires excretion. Typically fluids are administered to veterinary patients in volumes predicated on the needs of animals that are not anorexic. Careful observation of urine production in such patients is warranted. If the patient has normal renal concentrating ability but is producing large volumes of dilute urine, excessive fluid administration likely is a contributing factor. Reduction of fluid administration and careful observation are warranted in such patients.

50

Section  I  Critical Care

What Type of Fluid Should Be Given? The composition of a balanced fluid (e.g., lactated Ringer’s solution, Normosol-R, Plasma-Lyte 148) resembles that of extracellular fluid (ECF); whereas that of an unbalanced solution (e.g., normal saline) does not. Fluid preparations may be further classified as crystalloids or colloids. Crystalloids (e.g., 5% dextrose, 0.9% saline, lactated Ringer’s solution) are solutions containing electrolyte and nonelectrolyte solutes capable of entering all body fluid compartments. Colloids are large–molecular weight ­ substances that normally are restricted to the plasma compartment and include plasma, dextrans, hydroxyethyl starch (hetastarch), and hemoglobin-based oxygen-carrying fluids. Crystalloid solutions expand the plasma compartment with equal effectiveness, but 2.5 to 3 times as much crystalloid solution must be given (compared with a colloid solution) because the crystalloid is distributed to other sites (e.g., interstitial compartment, intracellular compartment). Pulmonary capillaries normally are more permeable to protein, resulting in a higher interstitial concentration of protein and more resistance to leakage of fluid from capillaries. Peripheral edema is more likely to occur after crystalloid administration than pulmonary edema because muscle and subcutaneous capillaries are less permeable to protein. Crystalloid solutions also can be classified as replacement or maintenance solutions. The composition of replacement solutions (e.g., lactated Ringer’s, NormosolR, Plasma-Lyte 148) resembles that of ECF. Maintenance solutions (e.g., Normosol-M, Plasma-Lyte 56) contain less sodium (40 to 60 mEq/L) and more potassium (15 to 30 mEq/L) than replacement fluids. Administering 5% dextrose (another commonly used crystalloid) is equivalent to giving water because the glucose is oxidized to CO2 and water. In fact, the main reason for giving 5% dextrose is to correct a pure-water deficit. Except in very small animals, 5% dextrose cannot be relied on to maintain daily caloric needs because it provides only 200 kcal/L. Most animals that require fluid therapy can be managed with a limited number of crystalloid and additive solutions. The most useful crystalloid solutions for routine use are a balanced replacement solution (e.g., lactated Ringer’s solution, Normosol-R, Plasma-Lyte 148), 0.9% saline, and 5% dextrose in water. Supplementation of crystalloid solutions with KCl may be necessary when body fluid losses have included large amounts of potassium. An empiric scale can be used to estimate the amount of potassium to add to parenterally administered fluids (Table 9-1). Other additive solutions include 50% dextrose, calcium chloride, calcium gluconate, potassium phosphate, 8.4% sodium bicarbonate, and water-soluble B vitamins. The choice of fluid to administer depends on the nature of the disease process and the composition of the fluid lost. The patient’s acid-base and electrolyte disturbances should be considered when choosing a fluid, and losses should be replaced with a fluid similar in volume and electrolyte composition to the fluid that has been lost. If clinical assessment of the patient suggests a fluid-responsive type of shock, the resuscitation phase of fluid therapy should be instituted. If the patient has abnormally low oncotic pressure or a disease that would benefit from lowvolume resuscitation, synthetic colloids should be con-

Table  9-1 Sliding Scale for Potassium Supplementation Serum Potassium Concentration (mEq/L)

mEq KCl to Add to 250 ml Fluid

30 days).

56

Section  I  Critical Care

Box  10-2 Gaps and Gradients in Acid-Base Disorders Estimation of Unmeasured Anions During Metabolic Acidosis Anion gap (AG) AG = (Na+ + K+) − (HCO3− + Cl−) Strong ion gap (SIG) SIG = [albumin] × 4.9 − AG (for dogs) SIG = [albumin] × 4.58 − AG + 9 (for cats) Interpretation Increased in • Acidosis caused by addition of unmeasured anions (lactic acidosis, ketoacidosis, renal failure, poisonings) • Hyperphosphatemia (hyperphosphatemic acidosis) Normal in • Hyperchloremic acidosis Decreased in • Hypoalbuminemia (hypoalbuminemic alkalosis) • SIG is not affected by changes in albumin concentration Estimation of Severity of Strong Ion Difference Alkalosis and Acidosis Caused by Chloride changes Chloride gap [Cl−]gap = 110 − [Cl−] × 146 / [Na+] (for dogs) [Cl−]gap = 120 − [Cl−] × 156 / [Na+] (for cats) Sodium-chloride difference Na− Cl = [Na+] − [Cl−] Only valid if [Na+] is normal Interpretation Increased in • Hypochloremic alkalosis Normal in • Hypoalbuminemic alkalosis Decreased in • Hyperchloremic acidosis Identifying the Origin of Hypoxemia in Respiratory Acid-Base Disorders Alveolar-arterial oxygen gradient (A-a) O2 gradient = 150 − 1.25PCO2 − PO2 Interpretation (in hypoxemic patients) Increased in • Pulmonary disease (e.g.; ventilation-perfusion inequality, right-to-left shunt) Normal in Alveolar hypoventilation (e.g.; central alveolar hypoventilation, abnormality in chest wall or respiratory muscles)

decrease of 1 g/dl in albumin concentration is associated with a decrease of 4.1 mEq/L in the AG (Constable and Stämpfli, 2005). The SIG is not affected by changes in albumin concentration, and an increase in ­unmeasured strong anions is suspected whenever SIG is less than −5 mEq/L. The SIG has not been clinically tested in dogs and cats, but its derivation is sound, and it is superior to the AG to detect increases in unmeasured strong anions in other species. Chloride Gap Chloride is the most important extracellular strong anion. Increases in chloride lead to metabolic acidosis by decreasing SID, whereas decreases in chloride cause metabolic alkalosis by increasing SID. Therefore plasma Cl− and HCO3− have a tendency to change in opposite directions in hypochloremic alkalosis and hyperchloremic acidosis. The contribution of Cl− to changes in BE and HCO3− can be estimated by calculating the chloride gap (see Box 10-2). Chloride gap values greater than 4 mEq/L are associated with hypochloremic alkalosis, whereas values less than −4 mEq/L are associated with hyperchloremic acidosis. Whenever sodium concentration is normal, the difference between the sodium and chloride concentrations ([Na+] − [Cl−]) can be used. Normally [Na+] − [Cl−] is approximately 36 mEq/L in dogs and cats. Values greater than 40 mEq/L are an indication of hypochloremic alkalosis, whereas values less than 32 mEq/L are associated with hyperchloremic acidosis. Alveolar-Arterial Oxygen Gradient Frequently patients with respiratory acidosis or alkalosis are also hypoxemic. When determining management options, it is important to differentiate between hypoxia from primary lung disease (e.g., ventilation-perfusion mismatching) and alveolar hypoventilation by calculating the alveolar-arterial oxygen gradient, or (A-a) O2 gradient. Values less than 15 mm Hg generally are considered normal. If the (A-a) O2 gradient is increased, a component of the hypoxemia results from ventilationperfusion mismatching, although it may be increased in some patients with extrapulmonary disorders. Clinically a normal gradient excludes pulmonary disease and suggests some form of central alveolar hypoventilation or an abnormality of the chest wall or inspiratory muscles. To increase the specificity of the test to diagnose ventilation-perfusion mismatch, only patients with (A-a) O2 gradient values more than 25 mm Hg should be considered abnormal (Johnson and de Morais, 2006). These patients are likely to have primary pulmonary disease, but extrapulmonary disorders cannot be ruled out completely.

Respiratory Acid-Base Disorders β-hydroxybutyrate, strong anions of renal failure) and weak (e.g., phosphate). The AG also is used to differentiate between hyperchloremic (normal AG) and high-AG metabolic acidoses. The AG in normal dogs and cats is mostly a result of the net negative charge of proteins and thus is heavily influenced by protein concentration, especially albumin. At plasma pH of 7.4 in dogs, each

Disorders of Pco2 Respiratory acid-base disorders are abnormalities in acidbase equilibrium initiated by a change in Pco2. The Pco2 is regulated by respiration: a primary increase in Pco2 acidifies body fluids and initiates the acid-base disturbance called respiratory acidosis, whereas a decrease in Pco2 alkalinizes body fluids and is known as respiratory alkalosis.

Chapter  10  Acid-Base Disorders 57



Respiratory Alkalosis Respiratory alkalosis or primary hypocapnia is characterized by decreased Pco2, increased pH, and a compensatory decrease in HCO3− concentration in the blood. Respiratory alkalosis occurs whenever the magnitude of alveolar ventilation exceeds that required to eliminate the CO2 produced by metabolic processes in the tissues. Common causes of respiratory alkalosis include stimulation of peripheral chemoreceptors by hypoxemia; primary pulmonary disease; direct activation of the brainstem respiratory centers; overzealous mechanical ventilation; and situations that cause pain, anxiety, or fear (Box 10-3). It is difficult to attribute specific clinical signs to respiratory alkalosis in the dog and cat. The clinical signs usually are caused by the underlying disease process and not by the respiratory alkalosis itself. However, in humans headache, lightheadedness, confusion, paresthesias of the extremities, tightness of the chest, and circumoral numbness have been reported in acute respiratory alkalosis. If the pH exceeds 7.6 in respiratory alkalosis, neurologic, cardiopulmonary,

Box  10-3 Principal Causes of Respiratory Alkalosis* Hypoxemia (Stimulation of Peripheral Chemoreceptors by Decreased Oxygen Delivery) • Right-to-left shunting • Decreased Pio2 (e.g., high altitude) • Congestive heart failure • Severe anemia • Pulmonary diseases with ventilation-perfusion mismatch • Pneumonia • Pulmonary thromboembolism • Pulmonary fibrosis • Pulmonary edema • Acute respiratory distress syndrome Pulmonary Disease (Stimulation of Stretch/Nociceptors Independent of Hypoxemia) • Pneumonia • Pulmonary thromboembolism • Interstitial lung disease • Pulmonary edema • Acute respiratory distress syndrome Centrally Mediated Hyperventilation • Liver disease • Hyperadrenocorticism • Gram-negative sepsis • Drugs • Corticosteroids • Central neurologic disease • Heatstroke Overzealous Mechanical Ventilation Situations Causing Pain, Fear, Anxiety *Modified from Johnson RA, de Morais HSA: Respiratory acid-base disorders. In DiBartola SP, editor: Fluid, electrolyte, and acid-base disorders, ed 3, Philadelphia, 2006, Elsevier, p 283.

and metabolic consequences may arise. Such a pH only can be achieved in acute respiratory alkalosis before renal compensation ensues. Alkalemia results in arteriolar vasoconstriction that can decrease cerebral and myocardial perfusion. In addition, hyperventilation (Pco2 < 25 mm Hg) causes decreased cerebral blood flow, potentially resulting in clinical signs such as confusion and seizures. Treatment of respiratory alkalosis should be directed at relieving the underlying cause of the hypocapnia; no other treatment is effective. Respiratory alkalosis severe enough to cause clinical consequences for the animal is uncommon. Hypocapnia itself is not a major threat to the well-being of the patient. Thus the underlying disease responsible for hypocapnia should receive primary therapeutic attention.

Respiratory Acidosis Respiratory acidosis, or primary hypercapnia, results when carbon dioxide production exceeds elimination via the lungs. Respiratory acidosis almost always is a result of respiratory failure with resultant alveolar hypoventilation and is characterized by an increase in Pco2, decreased pH, and a compensatory increase in blood HCO3− concentration. Respiratory acidosis and hypercapnia can occur with any disease process involving the neural control of ventilation, mechanics of ventilation, or alveolar gas exchange resulting in hypoventilation, ventilation-perfusion mismatch, or both. Acute respiratory acidosis usually results from sudden and severe primary parenchymal (e.g., fulminant pulmonary edema), airway, pleural, chest wall, neurologic (e.g., spinal cord injury), or neuromuscular (e.g., botulism) disease. Chronic respiratory acidosis results in sustained hypercapnia and has many etiologies, including alveolar hypoventilation, abnormal respiratory drive, abnormalities of the chest wall and respiratory muscles, and increased dead space (Box 10-4). Most clinical signs in animals with respiratory acidosis reflect the underlying disease process responsible for hypercapnia rather than the hypercapnia itself, and subjective clinical evaluation of the patient alone is not reliable in making a diagnosis of respiratory acidosis. In fact, patients with chronic, compensated respiratory acidosis may have very mild clinical signs. Neurologic signs may develop, particularly in acute hypercapnia, and seem to depend on the magnitude of hypercapnia, rapidity of change in CO2 and pH, and amount of concurrent hypoxemia. Acute hypercapnia causes cerebral vasodilation, subsequently increasing cerebral blood flow and intracranial pressure. Clinically the CNS effects of hypercapnia can result in signs ranging from anxiety, restlessness, and disorientation to somnolence and coma, especially when Pco2 approaches 70 to 100 mm Hg. The most effective treatment of respiratory acidosis consists of rapid diagnosis and elimination of the underlying cause of alveolar hypoventilation. For example, airway obstruction should be identified and relieved, and medications that depress ventilation should be discontinued if possible. A patient breathing room air at sea level will develop life-threatening hypoxia (PO2 < 55 to 60 mm Hg) before life-threatening hypercapnia. Thus supplemental oxygen and assisted ventilation are needed in treating acute respiratory acidosis. Although oxygen

58

Section  I  Critical Care

Box  10-4 Causes of Respiratory Acidosis Large Airway Obstruction • Aspiration (e.g., foreign body, vomitus) • Mass (e.g., neoplasia, abscess) • Tracheal collapse • Asthma • Obstructed endotracheal tube • Brachycephalic syndrome • Laryngeal paralysis/laryngospasm Respiratory Center Depression • Drug-induced (e.g., narcotics, barbiturates, inhalant anesthesia) • Neurologic disease (e.g., brainstem or high cervical cord lesion) Increased CO2 Production With Impaired Alveolar Ventilation • Cardiopulmonary arrest • Heatstroke Neuromuscular Disease • Myasthenia gravis • Tetanus • Botulism • Polyradiculoneuritis • Tick paralysis • Drug-induced (e.g., neuromuscular blocking agents, organophosphates, aminoglycosides with anesthetics) Restrictive Extrapulmonary Disorders • Diaphragmatic hernia • Pleural space disease (e.g., pneumothorax, pleural effusion) • Chest wall trauma/flail chest Intrinsic Pulmonary and Small Airway Diseases • Acute respiratory distress syndrome • Chronic bronchitis and asthma • Severe pulmonary edema • Pulmonary thromboembolism • Pneumonia • Pulmonary fibrosis • Smoke inhalation Ineffective Mechanical Ventilation (e.g., Inadequate Minute Ventilation, Improper CO2 Removal) *Modified from Johnson RA, de Morais HSA. Respiratory acid-base ­disorders. In: DiBartola SP, editor: Fluid, electrolyte, and acid-base disorders, ed 3, Philadelphia, 2006, Elsevier, p 283.

therapy may aid in the treatment of acute respiratory acidosis, oxygen may suppress the drive for breathing in patients with chronic hypercapnia. In chronic hypercapnia the central chemoreceptors become progressively insensitive to the effects of CO2, and O2 becomes the primary stimulus for ventilation. As a result, oxygen therapy may further suppress ventilation, worsening respiratory acidosis. If oxygen is administered, PO2 should be kept between 60 and 65 mm Hg because the hypoxic drive to breathing remains adequate up to this level. When

mechanical or assisted ventilation is begun, care must be taken to decrease Paco2 slowly. A sudden decrease in Pco2 can result in cardiac arrhythmias, decreased cardiac output, and reduced cerebral blood flow. It can also lead to posthypercapnic metabolic alkalosis and rapid diffusion of CO2 from cerebrospinal fluid into blood, thus quickly increasing cerebrospinal pH.

Metabolic Acid-Base Disorders Disorders of Atot Albumin, globulins, and inorganic phosphate are nonvol­ atile weak acids and collectively are the major contrib­ utors to Atot. Changes in their concentrations directly change pH and HCO3−. Common causes of Atot acidosis and alkalosis are presented in Box 10-5. Nonvolatile Buffer Ion Alkalosis Hypoalbuminemic alkalosis.  Hypoalbuminemic alkalosis is common in the critical care setting. In vitro a 1-g/dl decrease in albumin concentration is associated with an increase in pH of 0.093 in cats and 0.047 in dogs (Constable and Stämpfli, 2005). Presence of hypoalbuminemia complicates identification of increased

Box  10-5 Principal Causes of Nonvolatile Ion Buffer (Atot) Acid-Base Abnormalities* Nonvolatile Ion Buffer Alkalosis (Decreased Atot) Hypoalbuminemia • Decreased production • Chronic liver disease • Acute-phase response to inflammation • Malnutrition/starvation • Extracorporeal loss • Protein-losing nephropathy • Protein-losing enteropathy • Sequestration • Inflammatory effusions • Vasculitis Nonvolatile ion buffer acidosis (increased Atot) Hyperalbuminemia • Water deprivation Hyperphosphatemia • Translocation • Tumor cell lysis • Tissue trauma or rhabdomyolysis • Increased intake • Phosphate-containing enemas • Intravenous phosphate • Decreased loss • Renal failure • Urethral obstruction • Uroabdomen *From de Morais HSA, Constable PD: Strong ion approach to acid-base disorders. In DiBartola SP, editor: Fluid, electrolyte, and acid-base disorders, ed 3, Philadelphia, 2006, Elsevier, p 310.

Chapter  10  Acid-Base Disorders 59

unmeasured anions (e.g., lactate, ketoanions) because hypoproteinemia not only increases pH but also decreases AG. Thus the severity of the underlying disease leading to metabolic acidosis may be underestimated if the effects of hypoalbuminemia on pH, HCO3−, and AG are not considered. Treatment for hypoalbuminemic alkalosis should be directed at the underlying cause and the decreased colloid oncotic pressure. Nonvolatile Buffer Ion Acidosis Hyperphosphatemic acidosis.  Hyperphosphatemia, especially if severe, can cause a large increase in Atot, leading to metabolic acidosis. The contribution of phosphate to Atot (and AG) can be estimated by multiplying the phosphate concentration in milligrams per deciliter by 0.58. Thus a phosphorus concentration of 5 mg/dl is equivalent to 2.88 mEq/L at a pH of 7.4. The most important cause of hyperphosphatemic acidosis is renal failure. Metabolic acidosis in patients with renal failure is multifactorial but mostly is caused by hyperphosphatemia and increases in unmeasured strong anions. Treatment for hyperphosphatemic acidosis should be directed at the underlying cause. Sodium bicarbonate administered intravenously shifts phosphate inside cells and may be used as adjunctive therapy in patients with severe hyperphosphatemic acidosis.

Disorders of Strong Ion Difference Changes in SID usually are recognized by changes in HCO3− or BE from their reference values. It is important to understand that the change in SID from normal is equivalent to the change in HCO3− or BE from normal whenever the plasma concentrations of nonvolatile buffer ions (e.g., albumin, phosphate, globulin) are normal. A decrease in SID is associated with metabolic acidosis, whereas an increase in SID is associated with metabolic alkalosis. There are three general mechanisms by which SID can change (Table 10-2): (1) a change in the free water content of plasma; (2) a change in Cl−; and (3) an increase in the concentration of other strong anions.

Table  10-2 Mechanisms for Strong Ion Difference Changes* Disorder SID Acidosis ↓ In strong cations ↑ In strong anions ↑ Unmeasured strong anions SID Alkalosis ↑ In strong cations ↓ In strong anions

Mechanism

Clinical Recognition

↑ Free water (↓ sodium) ↑ Chloride

Dilutional acidosis

↓ Free water (↑ sodium) ↓ Chloride

Hyperchloremic acidosis Organic acidosis

Concentration alkalosis Hypochloremic alkalosis

*From de Morais HSA, Constable PD: Strong ion approach to acid-base disorders. In DiBartola SP, editor: Fluid, electrolyte, and acid-base disorders, ed 3, Philadelphia, 2006, Elsevier, p 310.

Strong Ion Difference Alkalosis There are two general mechanisms by which SID can increase, leading to metabolic alkalosis: an increase in Na+ or a decrease in Cl−. Strong cations other than sodium are tightly regulated, and changes of a magnitude that could affect SID clinically either are not compatible with life or do not occur. Conversely, chloride is the only strong anion present in sufficient concentration to cause an increase in SID when its concentration is decreased. Common causes of SID alkalosis are presented in Box 10-6. Concentration alkalosis.  Concentration alkalosis develops whenever a deficit of water in plasma occurs and is recognized clinically by the presence of hypernatremia or hyperalbuminemia. Solely decreasing the content of water increases the plasma concentration of all strong cations and strong anions and thus increases SID. Therapy for concentration alkalosis should be directed at treating the underlying cause responsible for the change in Na+. If necessary, serum Na+ concentration and osmolality should be corrected. Hypochloremic alkalosis.  When water content is normal, SID changes only as a result of changes in strong anions and can only increase with a decrease in Cl−. Hypochloremic alkalosis may be caused by an excessive loss of chloride relative to sodium or by administration of substances containing more sodium than chloride ­compared with normal extracellular fluid composition (see Box 10-6). The goal of treatment of metabolic alkalosis is to replace the chloride deficit while providing sufficient potassium and sodium to replace existing deficits, thus correcting the SID. Renal Cl− conservation is enhanced in hypochloremic states, and renal Cl− resorption does not return to normal until plasma Cl− concentration is restored to normal or near normal. Dehydrated patients should be rehydrated accordingly. The SID can be ­corrected with a solution containing adequate amounts

Box  10-6 Principal Causes of Strong Ion Difference Alkalosis in Dogs and Cats Concentration Alkalosis (Ø in Free Water: Recognizable by ≠ Na+) • Pure water loss • Inadequate access to water (water deprivation) • Diabetes insipidus • Hypotonic fluid loss • Vomiting • Nonoliguric renal failure • Postobstructive diuresis Hypochloremic Alkalosis (Ø Cl− corrected) • Excessive gain of sodium relative to chloride • Sodium bicarbonate administration • Excessive loss of chloride relative to sodium • Vomiting of stomach contents • Therapy with thiazides or loop diuretics *From de Morais HSA, Constable PD: Strong ion approach to acid-base disorders. In DiBartola SP, editor: Fluid, electrolyte, and acid-base disorders, ed 3, Philadelphia, 2006, Elsevier, p 310.

60

Section  I  Critical Care

of chloride (e.g., 0.9% NaCl, lactated Ringer’s solution, KCl-supplemented fluids). In cases in which expansion of extracellular volume is desired, intravenous infusion of 0.9% NaCl is the treatment of choice. SID Acidosis Three general mechanisms can cause SID to decrease, resulting in SID acidosis: (1) a decrease in Na+; (2) an increase in Cl−; and (3) an increased concentration of other strong anions (e.g., l-lactate, β-hydroxybutyrate). Common causes of SID acidosis are presented in Box 10-7. Dilutional acidosis.  Dilutional acidosis occurs whenever there is an excess of water in plasma and is recognized clinically by the presence of hyponatremia. Increasing the water content of plasma decreases the concentration of all strong cations and strong anions and thus SID. Large increases in free water are necessary to cause an appreciable decrease in SID. It has been estimated that in dogs and cats a decrease in serum Na+ concentration by 20 mEq/L is associated with a 5 mEq/L decrease in BE (de Morais and Leisewitz, 2006). Therapy for dilutional acidosis should be

Box  10-7 Principal Causes of Strong Ion Difference Acidosis in Dogs and Cats Dilution Acidosis (≠ in Free Water: Recognizable by Ø [Na+]) • With hypervolemia (gain of hypotonic fluid) • Severe liver disease • Congestive heart failure • Nephrotic syndrome • With normovolemia (gain of water) • Psychogenic polydipsia • Hypotonic fluid infusion • With hypovolemia (loss of hypertonic fluid) • Vomiting • Diarrhea • Hypoadrenocorticism • Third-space loss • Diuretic administration Hyperchloremic Acidosis (≠ [Cl−] Corrected) • Excessive loss of sodium relative to chloride • Diarrhea • Excessive gain of chloride relative to sodium • Fluid therapy (e.g., 0.9% NaCl, 7.2% NaCl, KClsupplemented fluids) • Total parenteral nutrition • Chloride retention • Renal failure • Hypoadrenocorticism Organic Acidosis (≠ Unmeasured Strong Anions) • Uremic acidosis • Diabetic ketoacidosis • Lactic acidosis • Toxicities • Ethylene glycol • Salicylate *From de Morais HSA, Constable PD: Strong ion approach to acid-base disorders. In DiBartola SP, editor: Fluid, electrolyte, and acid-base disorders, ed 3, Philadelphia, 2006, Elsevier, p 310.

directed at the underlying cause of the change in Na+. If necessary, serum Na+ concentration and osmolality should be corrected. Hyperchloremic acidosis.  Increases in [Cl−] can dec­ rease SID substantially, leading to so-called hyperchloremic acidosis. Hyperchloremic acidosis may be caused by chloride retention (e.g., early renal failure, renal tubular acidosis), excessive loss of sodium relative to chloride (e.g., diarrhea), or administration of substances containing more chloride than sodium compared with normal extracellular fluid composition (e.g., administration of KCl, 0.9% NaCl). Treatment of hyperchloremic acidosis should be directed at correction of the underlying disease process. Special attention should be given to plasma pH. Bicarbonate therapy can be instituted whenever plasma pH is less than 7.2. Organic acidosis.  Accumulation of metabolically produced organic anions (e.g., l-lactate, acetoacetate, citrate, β-hydroxybutyrate) or addition of exogenous organic anions (e.g., salicylate, glycolate from ethylene glycol poisoning, formate from methanol poisoning) causes metabolic acidosis because these strong anions decrease SID. Accumulation of some inorganic strong anions (e.g., SO42− in renal failure) will resemble organic acidosis because these substances decrease SID. The most frequently encountered causes of organic acidosis in dogs and cats are renal failure (uremic acidosis), diabetic ketoacidosis, lactic acidosis, and ethylene glycol toxicity. Management of organic acidosis should be directed at stabilization of the patient and treatment of the primary disorder. Patients with severe acidosis (pH 70 mm Hg, systolic pressure >110 mm Hg, central venous pressure (CVP) of 3 to 5 cm H2O), provide pain assessment and treatment (hydromorphone 0.05 to 0.2 mg/kg q4h or to effect), and measure urine output (1 to 2 ml/kg/hour); (2) assess at least every 8 hours serum electrolytes (goals are electrolytes within normal limits, with K+ >4.5 mmol/L), lactate (40 NRBCs per 100 white blood cells) are considered to be more likely to occur in dogs and less likely to occur in cats with lead toxicosis. Radiography may be helpful in identifying lead opacities within the GI tract. Lead lines, linear opacities in the epiphyses of long bones used to aid in diagnosis of lead toxicosis in humans, are not commonly found in domestic animals.

Pathologic Findings Few gross lesions have been described in dogs and cats with lead toxicosis. Necropsy may reveal the presence of lead objects especially in the GI tract. Histopathologic findings may include degenerative changes within the white matter of the brain and spongiosus of the cerebrum. In dogs degenerative changes in the kidney and liver may be seen, occasionally associated with intranuclear inclusion bodies.

Diagnosis The diagnosis of lead toxicosis can be difficult because the signs most commonly associated with this disease (anorexia, lethargy, vomiting) are nonspecific. Blood lead levels can be measured in a timely fashion and, when evaluated in light of compatible clinical signs, can be helpful in making a diagnosis. The widespread ­distribution

of lead throughout the body can result in fluctuating blood levels, and the level of lead in the blood may not be indicative of the total body burden. Some animals may have fairly high blood lead levels without significant clinical signs, whereas other animals may have significant clinical signs with only moderately elevated blood lead levels. Most animals have a background lead level of 10 to 15  mcg/dl (0.1 to 0.15  ppm); blood lead levels exceeding 30 to 35  mcg/dl (0.3 to 0.35  ppm) along with appropriate clinical signs are suggestive for lead toxicosis. Levels greater than 60  mcg/dl are generally considered diagnostic for lead toxicosis.

Treatment Management of lead toxicosis entails control of immediate clinical signs, removal of the source of lead, chelation therapy, supportive care, and removal of lead from the animal’s environment. Seizures should be managed with anticonvulsants such as diazepam or barbiturates (see Chapter 231). Similarly, vomiting and diarrhea should be managed, and any fluid and electrolyte abnormalities should be corrected as needed. GI decontamination must occur before chelation therapy since most chelators, with the exception of succimer, will actually enhance the absorption of lead from the GI tract. Sulfate-containing cathartics (magnesium sulfate, sodium sulfate) may be administered to aid in emptying the GI tract and to precipitate the lead as lead sulfate, which is poorly absorbed. Large lead-containing objects (e.g., lead sinkers, lead weights) may require removal via endoscopy or gastrotomy/enterotomy if they are too large to pass using bulking cathartics. When cats are suspected of exposure through grooming, thorough bathing should be performed. Chelation therapy is intended to bind lead into a soluble complex that will be excreted via the urine. Because of the nephrotoxic nature of most chelators, as well as the lead chelate, it is imperative that renal parameters be assessed before and during chelation and that adequate hydration be maintained during chelation. Chelation of asymptomatic animals that have elevated blood lead levels is not recommended because the chelator may increase the blood lead level and precipitate clinical signs. In cases of asymptomatic animals with elevated blood lead levels, decontamination and removal from the source of lead will allow the animal to eliminate the lead at its own pace. Available chelators include calcium disodium ethylene diamine tetracetate (Ca-EDTA), British anti-Lewisite (BAL), penicill­amine, and succimer (meso-2,3-dimercaptosuccinic acid). Ca-EDTA was the first chelator agent used for lead toxicosis, and it has an established track record in veterinary and human medicine. Sodium EDTA should not be used for chelation because it will bind serum calcium and cause hypocalcemia. Ca-EDTA is administered parenterally and may cause pain at the injection site. The dosage for dogs is 100  mg/kg/day for 2 to 5 days (not to exceed 2  g per dog per day), with each dose divided every 8 hours, diluted to a final concentration of 10  mg of Ca-EDTA per milliliter of 5% dextrose and administered subcutaneously at different sites. Expect clinical improvement within 24 to 48 hours. If further treatment

Chapter  28  Lead Toxicosis in Small Animals

129

is required after the first 5 days of therapy, a 5-day hiatus is recommended between treatments. Oral zinc supplementation may minimize the GI side effects of Ca-EDTA. The dose of calcium EDTA for cats is 27.5  mg/kg in 15 ml of 5% dextrose subcutaneously every 8 hours for 5 days. BAL is occasionally used in combination with Ca-EDTA, especially when significant CNS signs are present. BAL increases both urinary and biliary excretion of lead. BAL is contraindicated in animals with hepatic dysfunction, is nephrotoxic, and causes pain on injection. Other potential side effects of BAL include vomiting, hypertension, sulfur odor of breath, and seizures. The dosage of BAL is 2 to 5  mg/kg intramuscularly every 4 hours for 2 days, then every 8 hours for 1 day, and then every 12 hours until recovery. Penicillamine is an oral medication that eliminates the need for painful injections of BAL and Ca-EDTA. Penicillamine will bind essential nutrients such as zinc, iron, and copper; and its chelates may be nephrotoxic. Side effects reported with penicillamine include vomiting, fever, lymphadenopathy, and blood dyscrasias. Reported dosages for dogs are 30 to 110  mg/kg/day orally, divided every 8 hours for 7 days, and followed by a 7-day hiatus before reinstitution. Feline dosage is 125  mg per cat orally every 12 hours for 5 days. Succimer is an analog to BAL, and it has several advantages over BAL, Ca-EDTA, and penicillamine. Succimer can be administered orally or in vomiting animals rectally. Succimer is much less likely to cause nephrotoxicosis than the other three chelators; and it does not bind essential minerals such as copper, zinc, calcium, and iron. Succimer does not enhance absorption of lead from the GI tract as do the other chelators, and it has been shown to decrease lead absorption in studies with rats. Succimer also has a lower incidence of GI side effects. It does impart a mercaptan odor to the breath, similar to BAL. The dose is 10 mg/kg orally or rectally every 8 hours for 10 days. Following chelation therapy, blood lead levels may show a rebound within 2 to 3 weeks as a result of redistribution of lead from bone and tissue stores. Provided that this rebound is not associated with significant clinical signs, further chelation is not indicated. However, it is prudent to have the animal’s environment evaluated to be sure the rebound is not caused by re-exposure to lead. Supportive care involves providing adequate nutritional support since many animals with chronic lead toxicosis may be in a negative nutritional state because of chronic anorexia and vomiting. Hydration should be maintained, and force- or hand-feeding provided as needed. Examination of the animal’s environment is important to identify and remove any additional sources of lead so the animal does not become reexposed when reintroduced to its environment.

Prognosis Provided that prompt and appropriate care is pursued, including removing the source of lead from the animal’s environment, the prognosis for animals showing mild-tomoderate signs is favorable. Animals showing severe CNS signs or with repeated exposure to lead may merit a more guarded prognosis.

130

Section  II  Toxicologic Diseases

Public Health

Bibliography

The relative susceptibility of household pets makes them good sentinel animals for the potential for human exposure to lead. Veterinarians treating lead-intoxicated pets should ensure that pet owners are aware of the potential risk to family members, especially young children, from lead in the environment. Pet owners should be directed to their own health care professionals or public health officials for more information. Information on the risks of lead to human health can be found on the website of the Environmental Protection Agency (www.epa.gov).

Casteel SW: Lead. In Peterson ME, Talcott PA, editors: Small animal toxicology, ed 2, St Louis, 2006, Elsevier Saunders, p 795. Gwaltney-Brant SM: Lead. In Plumlee KH, editor: Clinical veterinary toxicology, St Louis, 2004, Mosby, p 204. Gwaltney-Brant SM, Rumbeiha WK: Newer antidotal therapies, Vet Clin Small Anim 32:323, 2002. Knight TE, Kent M, Junk JE: Succimer for treatment of lead toxicosis in two cats, J Am Vet Med Assoc 218:1946, 2001. Knight TE, Kumar MSA: Lead toxicosis in cats—a review, J Feline Med Surg 5:249, 2003.

CHAPTER 

29

Automotive Toxins Karyn Bischoff, Ithaca, New York

V

arious compounds for use in vehicle maintenance that are stored around the home have known toxic properties. An incomplete list of such chemicals includes ethylene glycol (EG), propylene glycol (PG), diethylene glycol (DEG), petroleum products, and methanol. EG is the most common component of antifreeze and unfortunately is the most common automotive product associated with poisoning in small animals. PG has been substituted for EG in antifreeze brands that are advertised as “safe” or “nontoxic.” In fact, PG is much less toxic to companion animals than EG but is not without adverse effects.

Ethylene Glycol EG is the most common cause of fatal poisoning in small animals (Thrall et al., 2006). EG is readily available in most households, is toxic in low doses, and is palatable. Toxicosis is most common in the late autumn or early spring, when radiators have been drained or open containers may be available to pets. Dogs occasionally chew through closed containers. Denatonium benzoate has been added to antifreeze to make it less palatable. California, New Mexico, and Oregon require addition of bittering agents to commercial antifreeze at the time of this writing. EG, or 1,2-dihydroxyethane, is a colorless, sweettasting liquid with a density of 1.113, a high boiling point (197.2° C), a low freezing point (−12.3° C) and

miscibility with water and alcohol. Other sources of EG include deicer, hydraulic brake and transmission fluids, additives in motor oils, paints, inks, wood stains and polishes, photographic solutions, and solvents used in the plastic industry.

Toxicity and Toxicokinetics The minimum lethal dose for EG in dogs is about 4.4 ml/ kg. Cats are more sensitive, with a minimum lethal dose around 1.4  ml/kg. Dogs are more frequently affected than cats, although cats may be more likely to become intoxicated through grooming activity after dermal contamination. Intact animals are more frequently affected. EG is absorbed rapidly from the gastrointestinal tract, particularly on an empty stomach. Absorption of injected or inhaled EG is also rapid. Peak plasma concentrations occur within 3 hours of ingestion. Metabolism of EG begins within hours of ingestion and occurs predominantly in the liver, with minor renal and gastric metabolism. The metabolic pathway of EG is illustrated in Fig. 29-1. The metabolism of EG to glycoaldehyde and then glycolic acid to glyoxylic acid are both rate-limiting steps. Oxalic acid is the most important final metabolite of EG. The plasma half-life of EG is approximately 3 hours, and elimination is almost complete within 24 hours. The parent compound— EG—and its metabolites, including glycolic acid and oxalic acid, are eliminated in the urine.

Chapter  29  Automotive Toxins



131

Ethylene glycol

Alcohol dehydrogenase

Glycoaldehyde

Glyoxal

Aldehyde dehydrogenase

Glycolic acid

Fig. 29-1  Hepatic metabolism of ethylene

glycol. Lactate dehydrogenase

Glyoxalic acid

Formic acid Glycine Oxalic acid Others Hippuric acid

Mechanism of Action In itself EG acts as a direct gastric irritant, causes central nervous system (CNS) depression, and may depress respiration. EG may increase serum osmolality, which may contribute to osmotic diuresis. The more severe effects associated with EG ingestion are caused by production of toxic metabolites. Acidosis is produced by such metabolic products of EG as glycolic acid and increased lactic acid production caused by nicotinamide adenine dinucleotide depletion during EG metabolism. Renal tubular damage is the most common cause of death in small animals poisoned with EG. Metabolites of EG are directly cytotoxic to renal tubular epithelium. Oxalic acid binds to calcium ions (Ca++) in the renal tubules (and other tissues) to form calcium oxalate crystals, leading to obstruction of tubules, epithelial damage, and hypocalcemia. Renal blood flow may be compromised in acidosis.

Clinical Signs EG toxicosis is described as having three stages, although early stages may be missed and stages may overlap. The first stage usually occurs within 30 minutes of exposure and usually lasts for 2 to 12 hours. Animals may vomit early. Polyuria and polydipsia are described in dogs, and cats are frequently polyuric. Ataxia and hyporeflexia may

be apparent, and animals are sometimes described as “inebriated” at this stage. Dogs may show apparent recovery from CNS depressive effects, but cats typically do not. The second stage usually occurs 8 to 24 hours after exposure and is related to acidosis. Clinical signs at this stage include CNS depression, changes in heart rate, hypothermia, muscle fasciculations, and sometimes coma. Cats may lose coordination in the pelvic limbs. Small animals that survive the first two stages enter the third stage, acute renal failure. This stage begins within 1 to 3 days of EG ingestion. Animals progress through oliguria to anuria. Signs of uremia may include oral ulcerations, salivation, vomiting, anorexia, and seizures. Palpation of cats often reveals large, painful kidneys. Serum chemistries often reveal an increased osmolal gap about an hour after EG ingestion, which may decline by 18 hours after exposure. The anion gap increases a few hours after exposure and can remain elevated for 48 hours in animals with acidosis. Phosphorus may be elevated early as a result of the phosphate additives in antifreeze and during renal failure. Hypocalcemia is reported in some patients. Serum urea nitrogen and creatinine are elevated 1 to 2 days after exposure in dogs and often within 12 hours in cats. Hyperkalemia occurs with the onset of renal failure. Urinalysis reveals isosthenuria as early as 3 hours after exposure as a result of osmotic

132

Section  II  Toxicologic Diseases

diuresis and low urine pH. Calcium oxalate crystals are evident within the first 8 hours, although crystalluria may be evident in healthy animals. Other findings may include hematuria, proteinuria, glycosuria, and granular and cellular casts.

Diagnosis Speed is of the essence in the diagnosis of EG toxicosis. The prognosis decreases precipitously with time if treatment is not instigated. EG concentrations begin to decline within 6 hours of exposure and may no longer be detectable in blood or urine by the time the animal presents to the veterinarian, which complicates the diagnosis. Various analytic tests have been used to confirm exposure to EG. Commercial test kits are available, but these may cross-react with certain compounds, including PG and glycerol from pet foods and pharmaceuticals. It is best to collect samples for testing before treatment begins. Test kits are unable to detect EG at concentrations below 50 mg/dl and thus may not be sensitive enough to use on cats or on dogs exposed more than 12 hours previously. Gas chromatography (GC) is frequently used to assay blood, urine, or kidney tissue for EG at diagnostic laboratories; but results are delayed by sample shipping and processing. Concurrent increase in the anionic and osmolal gap with the appropriate history and clinical signs is highly suggestive of EG toxicosis but does not always occur. Calcium oxalate monohydrate crystals are commonly found in the urine. Fluorescent dye is sometimes added to commercial antifreeze and may be seen with a Wood’s lamp in the urine or around the oral cavity or vomitus of exposed animals. However, other components of urine and some plastic containers may fluoresce. Finding the “halo effect” on renal ultrasound has been used to support an EG diagnosis. This is described as increased echogenicity in the cortex and medulla with decreased echogenicity at the corticomedullary junction and central medulla and occurs near the onset of anuria. Postmortem findings typical of EG exposure may include gastric hemorrhage; pulmonary edema; and pale, firm kidneys. Histologic changes include degeneration and necrosis of the epithelium of proximal convoluted tubules with intraluminal birefringent crystals. Chronicity is indicated by evidence of tubular regeneration, interstitial fibrosis, and glomerular atrophy and synechia. Oxalate crystals may be found in other tissues, including the liver and CNS.

Management The prognosis for EG toxicosis depends on the time of presentation. Animals treated early (stage 1) have an excellent prognosis, but the prognosis is poor for animals that present in renal failure (stage 3). Gastrointestinal decontamination, including emetics or gastric lavage and activated charcoal orally, has been recommended for animals within a few hours of EG ingestion. The benefit of such treatment is questionable because of the rapid absorption of EG.

Antidotes are available for EG. They act by inhibiting metabolism of EG by alcohol dehydrogenase (Bonagura, 2000). Antidotal treatment is most effective when started early but recommended if exposure has occurred within the past 32 hours. Fomepizole, or 4-methyl pyrazole, is preferred. This product is used in dogs at an initial dose of 20  mg/kg intravenously (IV); then 15  mg/kg IV is given at 12 and 24 hours, and 5  mg/kg is given IV at 36 hours. Cats require much higher doses of fomepizole than dogs. The recommended dose for cats is 125  mg/ kg IV initially and then 31.25  mg/kg every 12 hours for three more doses. Benefits of fomepizole include its lack of CNS depressant effects and the rarity of adverse effects. Fomepizole should never be used concurrently with ethanol therapy. Doing so will exacerbate clinical signs of ethanol toxicosis. Hemodialysis removes fomepizole from circulation. The prognosis is good if fomepizole therapy is started within 8 to 12 hours of EG ingestion for dogs or within 3 hours for cats. Fomepizole may not be immediately available; thus ethanol is still used therapeutically. Ethanol competitively inhibits metabolism of EG because of its affinity for alcohol dehydrogenase. It has been used for many years to treat EG toxicosis. Ethanol enhances CNS depression, and bolus dosing may cause respiratory suppression. Animals remain stuporous during treatment, requiring close monitoring and supportive care. Ethanol is usually given IV to maintain blood concentrations of 50 to 100 mg/dl. A 5.5-ml/kg dose of 20% ethanol is given every 4 hours for the first five treatments and then every 6 hours for the next four treatments in dogs, or dogs may be given a bolus dose of 1.3  ml of 30% ethanol followed by a constant infusion rate of 0.42  ml/kg/hour for 48 hours. Cats are given 5  ml/ kg of 20% ethanol IV every 6 hours for five treatments and then every 8 hours for four treatments. Patients should be monitored for hydration, urine production, acid-base status, serum urea nitrogen, creatinine, electrolytes, and body temperature at least daily. Bladder catheterization may be needed to monitor urine production. Fluid therapy is used to correct dehydration and electrolyte imbalances and promote diuresis. Saline is used to establish urine flow in anuric patients before potassium is added. Slow infusion of bicarbonate solution is required to correct acidosis. B vitamins (pyridoxine and thiamine) are routinely added to fluid therapy regimens in humans to promote glyoxylic acid metabolism. Peritoneal dialysis and hemodialysis have been used in veterinary and human medicine to treat renal failure, although fomepizole therapy must be adjusted. Tubular regeneration requires weeks or months, and the animal’s urine concentrating ability may be lost for more than a year.

Propylene Glycol PG, or 1,2 propandiol, is used in commercial antifreeze as an alternative to the more toxic EG. PG is also used as a deicer, hydraulic fluid, industrial solvent, humectant, and plasticizer, as well as in pharmaceuticals, cosmetics, and foods. It is commonly used as antifreeze in recreational vehicles. PG may be kept in large barrels in veterinary

clinics as a treatment for ketosis in ruminants. PG is classified as “Generally Recognized As Safe (GRAS)” by the U. S. Food and Drug Administration but is no longer used in cat food. PG has a density of 1.036 and is colorless, odorless, and almost flavorless. Like other antifreeze compounds, it has a high boiling point (189° C) and a low freezing point (−60° C) and is freely miscible with water and alcohol.

Toxicity, Toxicokinetics, and Mechanism of Action PG is less toxic than other glycols. Laboratory animal LD50s tend to fall near 20  ml/kg. The median lethal dose in experimental dogs is 9  ml/kg. Dogs tolerate a diet containing up to 20% PG with minimal clinical effects; however, 5% to 6% PG in the diet causes increased Heinz body formation in kittens and cats. High doses (approximately 40% of the diet) have been associated with mild neurologic signs, including ataxia and depression in cats. Toxicosis has been reported in humans, horses, and cattle and experimentally produced in cats, dogs, laboratory animals, goats, and chickens. I have seen apparently malicious poisoning in dogs using PG. PG is absorbed rapidly from the gastrointestinal tract and lungs, after injection, and through damaged skin. The volume of distribution is 0.5 L/kg in humans. About one third of PG is excreted unchanged in the urine; the rest is metabolized mostly in the liver and kidneys. Lactic acid is one major metabolite. PG may be conjugated to glucuronide in some species, but this metabolic pathway is inadequate in cats. Metabolites usually appear in the blood within 4 hours of exposure. PG may be excreted completely within a day in dogs. PG causes osmotic diuresis and a direct narcotic effect similar to ethanol but at about one third the potency. Lactic acid, the metabolic product, is formed in 2 isomers. The l- isomer enters the citric acid cycle and is metabolized. d-lactic acid is not readily metabolized and contributes to lactic acidosis. The mechanism of PG-mediated Heinz body formation and the dose-dependent decrease in survival time for feline erythrocytes are not completely understood.

Clinical Signs and Diagnosis Clinical signs in cats given high doses of PG include polyuria, polydipsia, and mild-to-moderate ataxia. Cats exposed to low dietary concentrations of PG may be asymptomatic but frequently have increased numbers of Heinz bodies, reticulocytes, and low red blood cell counts. Increased blood concentrations of d-lactic acid occur at higher dietary levels of PG. Clinical signs of acute PG toxicosis are referable to acidosis. Osmotic diuresis is present in animals after oral or parenteral administration of PG. Hypotension and circulatory collapse have been reported in cats and other species after parenteral overdosing. Pure PG is hyperosmolar and is likely to cause hemolysis if given undiluted IV. Postmortem lesions are nonspecific but may include a foul, garliclike odor to gastrointestinal contents after PG ingestion.

Chapter  29  Automotive Toxins

133

Diagnosis is based on history and clinical signs. Serum, urine, tissues, or the suspected source of PG may be analyzed using GC.

Management The prognosis for cats with chronic dietary exposure to PG is excellent. The number of Heinz bodies decreases once the source of PG is removed. The prognosis for acute toxicosis is fair to guarded, depending on the status of the animal. Decontamination using gastric lavage and activated charcoal may be effective if implemented very early, but gastrointestinal absorption is quite rapid. Dehydration, acidosis, and hypoglycemia are treated routinely as needed. Antioxidants such as vitamin E and vitamin C have been given to prevent erythrocyte damage without satisfactory results. N-acetylcysteine therapy has shown minimal benefit.

Diethylene Glycol DEG is an industrial solvent that may be present in brake fluid, hydraulic fluid, lubricants, and canned cooking fuels. High mortality is reported in epidemic human poisonings. DEG has a specific gravity of 1.118 and is a colorless, nearly odorless, palatable liquid.

Toxicity, Toxicokinetics, and Mechanism of Action The median lethal dose of DEG in laboratory animals ranges from 3.6 to 11.6  ml/kg; thus it is more toxic than PG but less so than EG. DEG is rapidly absorbed through the gastrointestinal tract or damaged skin. Peak plasma levels occur within an hour or two. DEG is metabolized primarily in the liver by alcohol dehydrogenase and aldehyde dehydrogenase. DEG and metabolites are excreted in the urine, and excretion is almost complete within 36 hours. The mechanism of action of DEG is not understood. There is a direct narcotic effect and renal damage, but oxalate crystals are not produced.

Clinical Signs and Diagnosis Clinical signs of DEG toxicosis are similar in most species. CNS depression and vomiting are reported early. These clinical signs appear to resolve but are followed by renal failure after 1 or more days. Cardiac abnormalities have been reported in some species. Serum chemistry findings include elevated urea nitrogen, creatinine, potassium, and evidence of lactic acidosis. Findings at necropsy usually include pale, swollen, mottled kidneys that bulge on cut surface. There is necrosis and degeneration of proximal convoluted tubular epithelium and tubular ectasia. Hepatic lipidosis and centrilobular necrosis have been reported in some species. Hemorrhage involving the pericardium, adrenal medulla, lungs, and pleura has been reported in humans, and I have seen similar lesions in one dog. Diagnosis is based on a history of exposure, clinical signs, and lesions. Tissues or suspected sources of DEG can be tested using GC, keeping in mind that elimination of DEG from the body is very rapid.

134

Section  II  Toxicologic Diseases

Management Animals presenting soon after exposure to DEG have a fair- to-guarded prognosis; but, once animals have evidence of renal failure, the prognosis is poor. Therapy includes symptomatic and antidotal treatments similar to those described for EG toxicosis.

Petroleum Compounds Petroleum compounds include a wide variety of products with variable physical and chemical characteristics. Such compounds include fuels such as propane, gasoline, kerosene, and diesel; solvents such as paint thinner and degreasers; lubricants such as motor oil; and carriers for pesticides, paints, and drugs. Animals may ingest spilled hydrocarbons or drink from open containers. Material spilled on the skin may be absorbed. Animals are occasionally given petroleum products intentionally.

Toxicity, Toxicokinetics, and Mechanism of Action Toxicity for petroleum products is highly variable and dependent on such factors as volatility, viscosity, and surface tension. Highly volatile compounds are associated with more morbidity and mortality because they are more readily aspirated into the lungs or absorbed into systemic circulation. Aspirated products having low viscosity penetrate deeper airways, and low surface tension further enhances spread within the pulmonary parenchyma. Absorption occurs through the gastrointestinal tract, skin, and lungs. Low–molecular weight compounds such as gasoline are better absorbed; whereas high–molecular weight compounds such as greases, mineral oils, and waxes are not well absorbed. Hydrocarbons are distributed to all major organs. Aliphatic hydrocarbons are oxidized in the liver to polar compounds that are more readily excreted. Respiratory excretion is important for volatile compounds, and highly volatile hydrocarbons may be excreted completely within 24 hours. Aspirated hydrocarbons dissolve lipids in cell membranes and cause degeneration and necrosis of the respiratory epithelium. Bacterial pneumonia may occur secondarily. Direct irritation of the skin and eyes is caused by the solvent effects of volatile hydrocarbons on cell membranes. Absorbed compound may interact with neuronal cell membranes to cause CNS depression.

Clinical Signs and Diagnosis Early clinical signs of ingestion include increased salivation, head shaking, and pawing at the muzzle. Vomiting and colic are typically seen with more volatile compounds, and diarrhea with heavier compounds such as mineral oil. Absence of emesis does not ensure that aspiration has not occurred. Signs of aspiration pneumonia may include choking, coughing, gagging, dyspnea, or cyanosis. Signs of CNS involvement include ataxia, confusion, depression, narcosis, and coma. Tremors and convulsions have been reported in a few cases. Cardiac arrhythmia and cardiovascular collapse have also been reported.

Animals that die after hydrocarbon ingestion frequently have gross lesions typical of aspiration pneumonia. Oily material may be visible in small airways. Secondary bacterial infection may be evident in animals that die late in the course of the disease. Centrilobular hepatic necrosis, myocardial necrosis, and renal tubular necrosis have been reported in animals surviving more than 24 hours according to Raisebeck and Daily (2006). If vomitus or stomach contents from an animal that has ingested hydrocarbons are mixed with warm water, the petroleum compounds float to the top. If skimmed with a paper towel, these compounds evaporate quickly and have a characteristic odor. This odor may be detectable on the breath or skin of the affected animal. Confirmation of exposure involves analysis of the gastrointestinal content or material on the skin and suspected source material via GC. Samples should be collected quickly and placed in glass containers or wrapped in foil to avoid contact with plastic and frozen until analysis can be performed.

Management The prognosis for animals that have ingested low-volatility compounds such as mineral oil or motor oil is good, assuming these products were not contaminated with other toxins such as pesticides or heavy metals. Management involves cage rest and observation. Animals that have no evidence of aspiration pneumonia 12 to 24 hours after ingestion have a good prognosis. Uncomplicated aspiration pneumonia is usually resolved after 2 weeks. However, the prognosis is poor if animals have extensive pulmonary lesions or present in a comatose state. Early management involves identification of the compound involved. The owner should bring the container or label of the suspected source of exposure. If contamination is dermal, a mild detergent bath and clipping of long or matted hair are useful. Animals should be kept warm during this process. Use of mechanic’s hand cleaner, lard, or similar substances may be required for removal of very viscous products such as tar. If the animal has ingested the material, gastrointestinal detoxification must be pursued with care. Emetics are usually contraindicated because of the risk of aspiration. Gastric lavage in the sedated, intubated animal and dosing with activated charcoal have been recommended. Instillation of mineral oil or vegetable oil to induce catharsis may increase the risk of aspiration pneumonia; thus it should be avoided. Monitoring of the exposed animal should include auscultation and thoracic radiography to assess pulmonary function. Aspiration pneumonia is treated symptomatically with cage rest, supplemental oxygen, and β2-agonists if needed for bronchospasm. Corticosteroids increase the risk of bacterial infection and should not be used. Prophylactic antibiotics should be considered. Cardiac function should be monitored, and arrhythmia treated as needed.

Methanol Methanol is used in automotive window washer fluids, gasoline antifreezes, canned cooking fuels, and various solvents. It is highly toxic to humans and other primates,

Chapter  30  Nicotine Toxicosis

causing formic acidosis, CNS disturbances, and retinal damage. Methanol is much less toxic to dogs and cats because they have an improved ability to metabolize formic acid using an enzyme system dependent on folate. In fact, it is less toxic in small animals than ethanol. Clinical signs of methanol toxicosis in dogs and cats are similar to those of ethanol inebriation. Treatment is based on monitoring and symptomatic and supportive care. Treatment with ethanol or fomepizole to inhibit alcohol dehydrogenase is discouraged.

References and Suggested Reading Bischoff K: Diethylene glycol. In Peterson ME, Talcott PA, editors: Small animal toxicology, ed 2, St Louis, 2006a, Elsevier Saunders, p 693. Bischoff K: Methanol. In Peterson ME, Talcott PA, editors: Small animal toxicology, ed 2, St Louis, 2006b, Elsevier Saunders, p 840.

CHAPTER 

135

Bischoff K: Propylene glycol. In Peterson ME, Talcott PA, editors: Small animal toxicology, ed 2, St Louis, 2006c, Elsevier Saunders, p 996. Bonagura JD, editor: Kirk’s current veterinary therapy XIII (small animal practice), Philadelphia, 2000, Saunders, p 212. Dalefield R: Propylene glycol. In Plumlee KH, editor: Clinical veterinary toxicology, St Louis, 2004a, Mosby, p 168. Dalefield R: Ethylene Glycol. In Plumlee KH, editor: Clinical veterinary toxicology, St Louis, 2004b, Mosby, p 150. Hill AS: Antioxidant prevention of Heinz body formation and oxidative injury in cats, Am J Vet Res 62:370, 2001. Raisebeck MF, Dailey RN: Petroleum hydrocarbons. In Peterson ME, Talcott PA, editors: Small animal toxicology, ed 2, St Louis, 2006, Elsevier Saunders, p 986. Ruble GR: The effect of commonly used vehicles on canine hematology and clinical chemistry values, J Am Assoc Lab Anim Sci 45:21, 2006. Thrall MA : Ethylene glycol. In Peterson ME, Talcott PA, editors: Small animal toxicology, ed 2, St Louis, 2006, Elsevier Saunders, p 986. Valentine WM: Short-chain alcohols, Vet Clin North Am Small Anim Pract 20:515, 1990.

30

Nicotine Toxicosis Wayne Spoo, Winston-Salem, North Carolina

N

icotine toxicosis is encountered occasionally in small animals, including dogs and cats. Toxic exposure is likely when a nicotine source is available and ingested in sufficient amounts or when dermal/ oral membrane exposure occurs. Nicotine can become available to animals from a variety of sources. This chapter focuses on nicotine toxicosis as it relates to consumption of nicotine replacement products (NRPs) and smoked/ unsmoked tobacco products.

Sources of Nicotine There are many potential sources of nicotine in nature. Table 30-1 lists possible sources of nicotine in the home. The tobacco plant Nicotiana spp. contains significant amounts of nicotine (1% to 6% by dry weight) both during the growing and harvesting cycles and after it has been dried and processed for inclusion in cigarettes, cigars, and other tobacco products. However, dietary plant sources also exist. Davis and colleagues (1991) and Domino, Hornbach, and Demana (1993) found that a number of common food items, principally found in the family Solanaceae (among others), contained varying amounts of nicotine but no cotinine (one metabolite of nicotine).

Others have reported that a number of plants other than tobacco contain nicotine, with estimates reported from 12 families and 24 genera, but at levels substantially lower than those found in tobacco. Why nicotine is present in plants is not known, but it is speculated to be a natural defense mechanism against bacteria, insects, and some animals. Dietary sources of nicotine are mentioned here as a potential source of exposure from homemade pet foods. Pet foods made with these products may provide an exposure mechanism to nicotine; however, there are no known reports of nicotine toxicosis in animals resulting from such exposures. No reports were identified that specifically linked toxicity related to inhalation of nicotine from cigarette smoke, although literature is available that describes the potential adverse health effects of cigarette smoke in pets.

Nicotine Replacement Products Food and Drug Administration (FDA)–approved NRPs are used by humans as an aid to quit smoking. The products come in a number of forms and delivery methods, are used to replace nicotine normally inhaled during

136

Section  II  Toxicologic Diseases

Table  30-1 Sources of Nicotine Source

Form

Specifics

Diet

Homemade pet foods, scraps, garbage Smoke Unsmoked tobacco products Smoked and unsmoked tobacco products Transdermal patches, gum, lozenges, etc.

Tomatoes (canned or fresh), green peppers, potatoes, eggplant, cauliflower Environmental tobacco smoke or “second-hand” smoke Cigars, cigarettes, snuff, chewing tobacco Cigarette butts (i.e., filter, plug wrap, tipping paper from smoked cigarettes) FDA-approved nicotine replacement products (see Table 30-2)

Tobacco Tobacco Cigarette structural materials Smoking cessation products FDA, Food and Drug Administration.

Table  30-2 Typical Nicotine Replacement Products Available in the United States Product Type

Product Name

Approximate Nicotine Content*

Availability

Patch

Habitrol, Nicoderm, Prostep, store brand or generic Nicorette, store brand or generic Nicotrol Nicotrol Commit, store brand or generic

7, 14, and 21 mg delivered dose/24 hr 2-4 mg/stick 0.5 mg/spray 4 mg/cartridge 4 mg/lozenge

Over-the-counter

Gum Nasal spray Inhaler Lozenge

Over-the-counter Prescription Prescription Over-the-counter

*Nicotine levels reported here are estimates for comparison only and may vary with brand and delivery method.

smoking, and are intended for short-term use. Table 30-2 is a partial list of some NRPs available in the United States and can be used by clinicians as a guideline to determine potential exposure to nicotine via the devices. A complete list of FDA-approved NRPs can be found at the FDA’s website. Nicotine dosage can be estimated when the number of gums, lozenges, or sprays/inhaler exposures are known. With respect to NRP patch products, the manufacturer label typically reports the dosage of nicotine delivered transdermally in humans over a 24-hour period. In the case of oral exposure in animals, the total amount of nicotine contained in each patch is of most relevance; however, dosage estimation can be a challenge. This information is not reported on the label and is known to vary between manufacturers. For example, Habitrol (Novartis) delivers 7, 14, and 21  mg of nicotine per 24 hours in humans; however, the patches contain total amounts of 17.5, 35, and 52.5  mg of nicotine, respectively. Nicoderm CQ (Glaxo-Smith-Kline) reports to deliver the same 7, 14, and 21  mg of nicotine per 24 hours in humans as well; however, the patches contain total amounts of 36, 78, and 114  mg of nicotine, respectively. Practitioners should consider calling the manufacturer directly to help determine the approximate ingested dose of nicotine or contact a poison control center to obtain information about total nicotine content of an ingested product.

Tobacco Whole cigarettes or cigarette butts are available sources of nicotine for pets within the household; tobacco products such as cigars, snuff, plug, and pipe tobacco are also potential sources. Nicotine content in tobaccos varies considerably among the types and brands of tobacco, and the list is too extensive to show here. Table 30-3 lists some general values for each of these types of tobacco and should be used as a guideline only. Other alkaloids in addition to nicotine are also found in tobacco at much lower levels,

Table  30-3 Guideline values for nicotine content by type of tobacco Product Type

Nicotine Content (dry weight value)

Cigarette butt Plug Loose-leaf snuff Cigarettes Moist snuff

1.4-1.7 mg 8 mg/g 7-12 mg/g 10-16 mg/rod* 3-11 mg/g

*Rod weights vary by brand and style. For comparison purposes, 0.78 g of cut filler tobacco/rod was assumed.

including nornicotine, anabasine, myosmine, nicotyrine, and anatabine, and are not thought to be of toxicologic concern.

Nicotine Toxicity Mechanism of Action, Kinetics, and Clinical Signs Nicotine is a weak base, which initially inhibits its absorption when ingested. Little absorption occurs in the stomach because of low pH but likely increases as the nicotine enters the less acidic intestines. Despite these considerations, substantial amounts of nicotine are systemically absorbed after ingestion. Relatively better absorption is obtained from dermal and oral mucosa exposure. Nicotine is metabolized in the liver. Nicotine mimics acetylcholine, acting at the parasympathetic and sympathetic ganglia and the neuromuscular junctions. Clinical signs of toxicity at less than lethal doses include hyperactivity, vomiting, and salivation. As the dose increases, tremors, dyspnea, tachycardia, muscle weakness/paralysis, and death from respiratory paralysis ensue.

Clinical Nicotine Toxicity Reports of clinical toxicity related to nicotine in animals are few, mainly limited to dogs. Less information is available for cats and birds. The median lethal dose (LD50) in dogs is reported to be 9.2  mg/kg (Franke and Thomas, 1932). Clinical signs of toxicity have been reported to begin in the 1- to 2-mg/kg range (Osweiler, 1990), and a minimum LD in dogs and cats was reported to be 20 to 100  mg. Using these data, a 40-lb dog would need to ingest approximately 11 cigarettes to reach the LD50 dose (assuming 100% absorption) or one cigarette to achieve signs of clinical toxicity. Vig (1990) reported nicotine toxicosis in a 12-weekold toy poodle that ingested approximately 1 tbsp of liquid from a spittoon. The dog presented with constricted pupils, central nervous system dysfunction (incoordination, trembling, opisthotonus), salivation, and increased heart rate. Blood nicotine and cotinine levels were not reported. Nicotine toxicosis was the most likely diagnosis; however, further characterization of the liquid that was ingested for nicotine content or other potentially toxic components was not reported. Treatment was symptomatic with oral activated charcoal, intravenous diazepam, and sodium bicarbonate. Fourteen hours after admission, the dog’s clinical appearance was normal. Matsushima, Prevo, and Gorsline (1995) reported on the adverse effects of nicotine after topical and oral administration of three transdermal nicotine products. Nicotine doses ranged from 1 to 2  mg/kg/day when dosed topically, resulting in plasma nicotine levels as high as 43  ng/ml. Two of 12 dogs exposed via this route exhibited mild clinical signs consisting of excessive salivation and emesis. When the patches were administered orally (2.8  mg/kg for one patch; 13.4  mg/kg for two patches) over 25 to 57 hours, mean plasma nicotine levels peaked within 1 to 2 hours after administration, with plasma nicotine levels roughly similar to that of the dermal route.

Chapter  30  Nicotine Toxicosis

137

Two of the 12 dogs receiving two patches orally vomited. Other physiologic observations (e.g., heart rate, blood pressure) were not reported. Cardiovascular effects related to nicotine have also been reported. Huckabee and associates (1993) reported increased regional blood flow in anesthetized dogs dosed with 3 to 100  mg/kg of moist snuff placed in the right buccal space. The nicotine content on the moist snuff on a per gram basis was not reported; thus the exact dose was unknown (see Table 30-3 for an estimated value). Moist snuff increased blood in the buccal tissue at the site of application, with a decrease in blood flow in the opposite (undosed) buccal space. In contrast to oral exposure scenarios, increases in aortic blood pressure, central venous pressure, and left ventricular diastolic and systolic pressure tended to increase as the dose of snuff increased. Similar cardiovascular findings in dogs were reported by Herman and colleagues (2001) using various nicotine patches and Skoal Bandits (moist snuff in a small pouch) placed in the buccal cavity. Nicotine has also been reported to alter renal function in dogs (Pawlik, Jacobson, and Banks, 1985) and elevations in serum angiotensin-converting enzyme (Sugiyama, Yotsumoto, and Takaku, 1986). It is difficult to describe a typical toxicity scenario associated with nicotine-containing products related to household pets because of a lack of specific poisoning cases and dose information. It is reasonable to conclude that clinical signs related to nicotine toxicosis are likely to be less severe when ingesting cigarettes and/or cigarette butt(s) if treated quickly after ingestion. Signs manifested after ingestion of NRPs are likely to be more overt if the products are damaged and more nicotine is available for absorption versus the intact product (see Table 30-2) or if treatment is delayed. Animals that chew on tobacco products and do not swallow or are otherwise exposed via the oral mucosa only (i.e., puncturing a nasal inhaler) may also exhibit more severe clinical signs, which again depends on the product form.

Treatment of Nicotine Toxicosis There is no specific treatment for nicotine poisoning; thus therapy is symptom specific. Given the basic nature of nicotine, oral absorption for the stomach is expected to be low, increasing as the nicotine reaches the intestinal tract. If ingestion of nicotine-containing products is suspected/known, evacuation of the gastric contents (if not contraindicated) should be instituted as soon after exposure as possible (see Chapter 24). Gastric lavage, activated charcoal therapy, and supportive care (e.g., fluid therapy, respiratory support) should also be considered. Atropine and benzodiazepines can also be used to counter parasympathetic stimulation. In cases of dermal exposure the nicotine source should be removed, the skin thoroughly washed with soap and water, supportive care administered, and the animal observed for signs of nicotine toxicosis. Overall, consumption of nicotine from tobacco or NRPs is an occasional poisoning scenario in household pets. Clinical signs related to nicotine toxicity are dose, product, and route dependent. A thorough history related to intoxication, including identification of the specific

138

Section  II  Toxicologic Diseases

nicotine form, estimation of nicotine dose, and time since exposure, is useful in determining treatment protocols and prognosis. Clinicians are encouraged to use Table 30-2 as a guide in determining how much nicotine the animal potentially received. Treatment should be implemented as quickly as possible, and supportive therapy instituted as appropriate.

References and Suggested Reading Centers for Disease Control and Prevention: Determination of nicotine, pH, and moisture content of six US commercial moist snuff products—Florida, MMWR 48(19):398, 1999. Davis RA et al: Dietary nicotine: a source of urinary cotinine, Food Chem Toxicol 29(12):821, 1991. Domino EF, Hornbach E, Demana T: Relevance of nicotine content of common vegetable to the identification of passive tobacco smokers, Med Sci Res 21:571, 1993. Food and Drug Administration website: http://www.accessdata. fda.gov/scripts/cder/drugsatfda/index.cfm. Franke JE et al: Determination of nicotine in tobacco: collaborative study, Beitrage Zur Tabakforschung International Contributions To Tobacco Research 19:251, 2001.

CHAPTER 

Franke FE, Thomas JE: A note on the minimal fatal dose of nicotine for unanesthetized dogs, Proc Soc Exp Biol Med 29:1177, 1932. Herman EH et al: Cardiovascular effects of buccal exposure to dermal nicotine patches in the dog: a comparative evaluation, Clin Toxicol 39:135, 2001. Huckabee KD et al: Effects of snuff on regional blood flow to the cheek and tongue of anesthetized dogs, Oral Surg Med Oral Pathol 76:729, 1993. Matsushima D, Prevo ME, Gorsline J: Absorption and adverse effect following topical and oral administration of three transdermal nicotine products to dogs, J Pharm Sci 84: 365, 1995. Osweiler GD: Toxicology, Media, Pa, 1996, Williams & Wilkins. Osweiler GD et al: Clinical and diagnostic veterinary toxicology, ed 3, Dubuque, Ia, 1976, Kendall Hunt Publishing. Pawlik WW, Jacobson ED, Banks RO: Actions of nicotine on renal function in dogs, Proc Soc Exp Biol Med 178 585, 1985. Richter P, Spierto FW: Surveillance of smokeless tobacco nicotine, ph, moisture, and unprotonated nicotine content, Nicotine Tob Res 5:885, 2003. Sugiyama Y, Yotsumoto H, Takaku F: Increase in serum angiotensin-converting enzyme level after exposure to cigarette smoke and nicotine infusion in dogs, Respiration 49:292, 1986. Vig MM: Nicotine poisoning in a dog, Vet Hum Toxicol 32:573, 1990.

31

Recently Recognized Animal Toxicants Jocelyn A. Mason, Chambly, Québec, Canada Safdar A. Khan, Urbana, Illinois Sharon M. Gwaltney-Brant, Urbana, Illinois

Minoxidil Minoxidil, a hypotensive agent, has been used as a vasodilator and as a topical solution to enhance localized hair growth in humans. Minoxidil alters potassium channels in vascular smooth muscle, resulting in vasodilation and hypotension. The mechanism of enhanced hair growth is not entirely understood, but minoxidil may increase epithelial cell proliferation at the follicular base or vasodilation of scalp vasculature or both. Oral formulations of minoxidil are well absorbed orally, with peak plasma concentrations within 2 hours in dogs. When applied topically, 0.3% to 4.5% of the dose is absorbed systemically. Kinetic information regarding

ingestion of the topical product is not available. Although the plasma concentration declines rapidly after peak concentrations, the peak hypotensive effect is delayed by several hours and persists for at least 24 hours after exposure. In humans a large percentage of oral minoxidil is metabolized by conjugation with glucuronic acid. Consequently minoxidil elimination may be delayed in cats if cats eliminate minoxidil in the same way. In experimental studies in dogs, short-term oral administration of minoxidil resulted in a variety of hemorrhagic and necrotic myocardial lesions, but dermal application of the topical product did not cause cardiac lesions or hypotension. To date significant hypotension in clinical canine cases of minoxidil exposure has only occurred

through ingestion of tablets. Oral exposures to topical products have primarily produced vomiting and lethargy in dogs. Two cats that had minoxidil solution applied topically showed lethargy and dyspnea within 36 hours of exposure, and pulmonary edema and pleural effusion were identified on radiography. Both cats died in spite of aggressive supportive care. Histopathology confirmed acute myocardial ischemia and edema resulting in severe cardiac compromise, pulmonary edema, and pleural effusion. Whether the minoxidil was absorbed dermally or ingested via grooming behavior is not clear. At least two instances of cats developing hypotension (one with pleural effusion) after licking the treated hair of their owners have been reported to the ASPCA Animal Poison Control Center (ASPCA Animal Poison Control Center, unpublished data). One of these cats died, and the other was lost to follow-up. Because of the potential for serious cardiovascular compromise, exposures to minoxidil should be managed aggressively. Oral exposures to minoxidil should be managed with gastric emptying followed by activated charcoal. Rinsing the oral cavity with water may bring some relief because the topical solution may be irritating to oral mucous membranes. Dermal exposures should be decontaminated with bathing in a liquid dishwashing detergent. Bathing may be effective as long as 48 hours after topical exposure because of delayed absorption of topical products. Cardiovascular and respiratory systems should be monitored closely for 36 to 48 hours. Pulmonary edema should be managed using furosemide or other standard treatment. Thoracocentesis may be required to remove pleural effusion and improve respiration. Intravenous fluid therapy is indicated if hypotension develops, although care must be used in managing fluid rates in cats with pulmonary edema. Pressor agents may be useful in hypotensive animals that do not respond to fluid administration alone. The use of colloids (Hetastarch, Gensia Sicor Pharm) at a 5-ml/kg bolus along with dopamine, intravenous crystalloids, and thoracocentesis resulted in successful resolution of pleural effusion and hypotension in one severely affected cat (ASPCA Animal Poison Control Center, unpublished data). The prognosis for animals exposed to minoxidil depends on the extent of exposure, severity of clinical signs, and promptness and aggressiveness of treatment. Animals showing significant cardiac or respiratory signs should be considered to have a guarded prognosis.

Xylitol Xylitol is a 5-carbon sugar-alcohol sweetener that is increasingly used in sugar-free products such as gums, baked goods, and candies. In humans xylitol does not cause significant increases in blood insulin or glucose levels. However, in dogs oral xylitol can cause a rapid and dose-dependent increase in blood insulin concentrations, with a concurrent drop in blood glucose concentration. Some dogs that have ingested larger amounts of xylitolcontaining products have subsequently developed hepatic necrosis. The mechanistic cause of hepatic lesions has not

Chapter  31  Recently Recognized Animal Toxicants

139

been established; however, a theory of interference with hepatocellular adenosine triphosphate production has been raised. The toxicity of xylitol to cats is not known. Chewing gums with xylitol as the primary or sole sweetener contain about 0.3 to 0.4  g of xylitol per piece. Xylitol doses greater than 100  mg/kg (0.1  g/kg) have been associated with hypoglycemia; and doses greater than 1000  mg/kg of body weight have been associated with hepatic necrosis in dogs. Clinical signs of hypoglycemia in dogs may occur within 30 minutes of ingesting xylitol-containing products. These signs may include vomiting, lethargy, disorientation, ataxia, tremors, collapse, and seizures. Other signs that may occur include weakness, diarrhea, abdominal pain, vocalization, tachypnea and fasciculation. Clinical pathologic findings reported in dogs ingesting xylitol include hypoglycemia, hypokalemia, and mild hypophosphatemia. Occasionally hypoglycemia may be prolonged beyond 12 hours, especially in cases of xylitol-containing gum ingestion. Evidence of hepatic insufficiency may be seen by 8 to 12 hours after exposure, characterized by elevations in hepatic enzyme levels. Some dogs develop transient elevations of liver enzymes; whereas others progress to acute liver failure, hemorrhage, dissemination, and death. Not all dogs that develop acute hepatic failure after xylitol ingestion show signs of hypoglycemia. Some simply become acutely ill 48 hours after ingestion of xylitol. Serum chemistry reveals extreme elevations in alanine aminotransferase, elevated bilirubin, and prolonged prothrombin times (PTs) and partial thromboplastin times (PTTs). Some cases show initial hypophosphatemia with terminal hyperphosphatemia. Management of xylitol exposures in dogs includes gastrointestinal (GI) emptying in asymptomatic dogs. The use of activated charcoal is debatable since results of one in vitro study have indicated that adsorption of xylitol by activated charcoal is limited and unreliable. Because of the potential for significant clinical signs to develop within 30 minutes, emesis and activated charcoal administration must be performed with care to avoid the risk of aspiration. Frequent small meals in asymptomatic animals with frequent monitoring of serum glucose levels for at least 6 to 12 hours are important. Administration of 5% dextrose intravenously (IV) may be needed to maintain normal blood glucose concentrations. Potassium supplementation may be required if potassium levels drop below 2.5  mEq/L. In dogs ingesting potentially hepatotoxic doses of xylitol (>1000  mg/kg), an initial bolus of intravenous dextrose should be considered, followed by continuous-rate infusion of dextrose for 24 hours, with monitoring of liver enzymes and PT/PTT for 48 to 72 hours. The use of hepatoprotectants (e.g., S-adenosylmethionine) should be considered in dogs developing evidence of injury; although evidence of efficacy of these products in preventing liver injury is lacking, their antioxidant effects may help minimize secondary oxidative hepatic injury. Other standard treatments for hepatic injury (e.g., lactulose, antibiotics) may be required to manage liver injury. The prognosis for xylitol toxicosis depends on the dose ingested, clinical signs, and the response to therapy. Hypoglycemia generally responds well to dextrose

140

Section  II  Toxicologic Diseases

treatment, but prolonged seizure activity may result in hyperthermia and disseminated intravascular coagulopathy. The development of hepatic necrosis and coagulopathy warrants a guarded prognosis; hyperphosphatemia may be associated with poorer prognosis in dogs.

Expandable Polyurethane Glue Toxicity Expandable polyurethane glues are available as industrialstrength wood glues marketed as Gorilla Glue, Elmer’s ProBond Polyurethane Glue, or insulating foam sealants. These products contain diphenylmethane diisocyanate or polymethylene polyphenol isocyanate in various concentrations. The terms isocyanate and diisocyanate are usually listed in the active ingredient section of most expandable polyurethane glues. Most glue or adhesive exposures in animals are acute and accidental. All animal species are susceptible; however, dogs are more likely to be involved, presumably because of their chewing habits. Dermal exposure in cats can lead to significant oral exposure after grooming. Ingestion of expandable polyurethane glues (isocyanates) can form an expanding gastric foreign body. This is more likely to occur in dogs that chew the bottle of glue rather than lick or ingest products covered with the glue. An animal that ingests already polymerized and dried glue is not likely to experience foreign body obstruction. Most clinical signs develop within 12 hours of exposure but may range from 15 minutes to 20 hours. Radiographic evidence of gastric outflow obstruction can be evident within 24 hours of exposure. The most commonly reported clinical signs of expandable polyurethane toxicosis include vomiting, retching, anorexia, lethargy, visible abdominal distention or presence of a large firm mass on palpation, diarrhea, tachypnea, and dehydration. Following ingestion, the glue polymerizes into a large, friable, black-to–dark brown foreign body. The foreign body may resemble kibble filling the entire stomach. Radiographic findings seen 4 to 5 hours after exposure include a large radiopaque, mottled density in the stomach; gastric dilation; or both. It has been suggested that the expandable polyurethane glue is hygroscopic in nature and absorbs water from the stomach. Warm body temperature may also play a role in glue expansion. Diagnosis is made based on history of exposure, types of clinical signs present, and endoscopic or radiographic evidence of a foreign body. Before instituting any treatment, it is important to confirm that the patient has been exposed to expandable polyurethane glue versus nonexpandable glue. Cyanoacrylates (Superglue, Krazy glue) that contain ethyl-2-cyanoacrylate or poly (methylmethacrylate) and white glues containing polyvinyl acetate in various concentrations are not known to cause foreign body obstruction following ingestion. Reading the label of the product can be extremely helpful in determining the type of the glue involved. Most expandable glues have the word isocyanate or diisocyanate written in the active ingredient section. The treatment of expandable polyurethane glue toxicosis involves (1) decontamination with the aim of preventing formation of a foreign body; (2) determination of

the nature and severity of the foreign body; (3) surgical removal of the foreign body if necessary; and (4) supportive care. With dermal exposure, the area should be washed thoroughly with a mild dishwashing detergent. The hair is clipped, or the glue manually removed using a toenail clipper. Once the glue dries, it is not normally irritating to the skin. Induction of emesis with hydrogen peroxide or apomorphine in dogs following oral exposure is debatable. The fear is that, if part of the glue is lodged in the esophagus, it could lead to esophageal obstruction. In our opinion emesis could be tried cautiously under veterinary supervision only if exposure has been within 1 hour. The animal should be given a small amount of water or food after vomiting to clear the esophagus. Dilution with milk or activated charcoal is not recommended because it may enhance both the potential of foreign body formation by providing liquid for the adhesive to absorb and the risk of aspiration from vomiting. It may be necessary to perform a gastrotomy to remove a gastric foreign body. Abdominal radiographs or endoscopic examination of the stomach may help determine the presence of a foreign body and esophageal and gastric mucosal damage (irritation, ulcers, rupture). Excellent results (100% recovery) have been achieved in dogs with appropriate medical and surgical intervention. Systemic toxic effects other than foreign body obstruction have not been described. Anesthesia for performing gastrotomy can be induced with propofol (4  mg/kg IV) and maintained with isoflurane. Atropine sulfate is used as a preanesthetic agent (0.02  mg/kg IV). After removal of the foreign body, any damage to the stomach mucosa (i.e., presence of adhesions, ulcers, or rupture) is assessed. Sucralfate, an H2 antagonist such as famotidine or cimetidine, and broadspectrum antibiotics are administered after gastrotomy for 10 days or longer, as needed. Metoclopramide can be used for controlling vomiting. Food and water intake should be restricted for the first 12 to 24 hours after surgery. Pain should be controlled, and supportive care given, including intravenous fluids as needed. Several days may be needed for complete recovery after the surgery. Stomach rupture, torsion, and peritonitis are some possible complications following surgery.

Brunfelsia spp. Toxicosis The genus Brunfelsia belongs to the Solanaceae family. This plant is an erect, compact, evergreen shrub that grows to about 1.5 to 2 feet in height and diameter. Brunfelsia is native to South and Central America and the West Indies. The genus has about 40 different species. All species of Brunfelsia in the United States are ornamentals; consequently they are found outside in gardens in warmer regions and inside as potted plants in colder states. The showy flowers appear in clusters. The deep purple flowers gradually change to lavender and then to white over a 3-day period. One plant may have all three flower colors (purple, lavender, and white) at the same time. Browngreen berries can be found in summer and autumn. Each seed pod may possess about 20 small hard seeds.

Although only a few Brunfelsia species (B. calcyina var. floribunda, commonly known as yesterday-today-andtomorrow; B. pauciflora; B. australis; B. bondora) have been implicated in animal poisoning cases, all species of this genus should be considered toxic to all animals. All parts (flowers, leaves, berries, and seeds) are toxic. Dogs appear to be particularly attracted to the berries. There are a few case reports of Brunfelsia toxicosis reported in cattle, dogs, rats, and mice. Because of the increased popularity and availably of Brunfelsia species in the United States, the numbers of poisoning cases from Brunfelsia in the dog appear to be increasing. For example, in 2005 alone, nine Brunfelsia toxicity cases were reported to the ASPCA Animal Poison Control Center. Seven of these cases were reported from California, one was from Oregon, and one was from Texas. Most commonly reported clinical signs included seizures, hypersalivation, ataxia, tremors, head shaking, diarrhea, and lethargy. Death was reported in one dog. The onset time of clinical signs in Brunfelsia toxicosis in dogs may occur within 15 minutes to several hours after the exposure. Clinical signs may start with agitation, nervousness, or excitement followed by tremors, shaking, muscular rigidity, paddling, and tonic-clonic seizures. The tonic-clonic seizures and other clinical signs such as muscular rigidity or sawhorse stance may resemble those caused by strychnine poisoning. Clinical signs may last from a few hours up to several days. Brunfelsia poisoning does not seem to cause any significant hematologic, chemistry, or pathologic changes in animals. Although several biologically active compounds have been isolated from Brunfelsia species, two compounds of interest are hopeanine and brunfelsamidine. Hopeanine causes decreased activity, paralysis, seizures, and hypersensitivity in rodents; brunfelsamidine produces excitement, tonic and clonic seizures, and death. Brunfelsamidine may prove to be the toxin responsible for neurotoxicity in animals. Other unidentified toxins from B. calcyina var. floribunda are water soluble and maintain toxicity for 4 months. Diagnosis of Brunfelsia toxicosis in dogs may be made based on a history or evidence of exposure to the plant (flowers, leaves, berries, or seeds present in the vomitus, or stool) and presence of characteristic central nervous system (CNS) signs (muscular rigidity, paddling, tonicclonic seizures). Differential diagnosis list should include strychnine, metaldehyde, methylxanthine, organochlorine pesticides, lead, and illicit drug toxicosis. The objectives of treatment are decontamination, seizure control, and supportive care. If the animal is presented with CNS signs, the first step should be to stabilize it (control seizures as described later in this paragraph) before starting decontamination or supportive care. Emesis can be induced when no clinical signs are present and exposure is known to have been within 2 hours. Emesis can be induced with hydrogen peroxide or apomorphine and should be followed by administration of activated charcoal. Repeated doses of charcoal every 6 to 8 hours can be useful if seeds or fruit have been ingested. Gastric or enterogastric lavage followed by charcoal administration can be considered when large amounts of seeds or berries have been consumed. Seizures can be controlled

Chapter  31  Recently Recognized Animal Toxicants

141

with pentobarbital sodium IV; it should be given to effect and repeated as needed or with methocarbamol (100 to 200  mg/kg IV; maximum dosage of 330  mg/kg/day). Propofol (4-6  mg/kg IV) or diazepam (with variable success) may be used at 1 to 2  mg/kg IV. Isoflurane gas anesthesia should be tried if seizures are not controlled with the preceding treatment measures. Severely affected animals should be intubated, and artificial respiration provided; they should be kept in a dark and quiet place. The animal should be monitored for hyperthermia and treated as needed with cooling bath or fans. Intravenous fluid diuresis may be required for 1 to 2 days or longer. Complete recovery may take several days or a week or longer.

Paintball Toxicosis Dogs seem to be attracted to paintballs. They have been known to eat as many as 500 paintballs at one time. Paintballs are available in different colors, and one box may contain more than 1000 paintballs. Active ingredients vary, depending on the manufacturer, but often include polyethylene glycol, glycerol (glycerin), gelatin, sorbitol, dipropylene glycol, water, dye, titanium dioxide (found in most acrylic paints), and food coloring. Some paintballs have polyethylene glycol available as 94% and dipropylene glycol as 64%; however, concentrations of most ingredients are not listed on the label. The most commonly reported clinical signs associated with paintball ingestion in dogs include vomiting with or without paint, ataxia, diarrhea, and tremors. Other less frequently seen clinical signs may include tachycardia, weakness, hyperactivity, hyperthermia, blindness, and seizures. Most commonly reported electrolyte changes include hypernatremia (22%), occasionally hyperchloremia, and hypokalemia. Clinical signs can develop within 1 hour to several hours after exposure, and ingestion of as little as 15 paintballs has led to development of clinical signs. The exact mechanism of hypernatremia or other electro­ lyte changes following paintball ingestion is not known. It has been suggested that the presence of osmotically active agents such as polyethylene glycol, glycerol, and sorbitol in paintballs can cause fluid shifts, moving the water from the body tissues into the bowel lumen. Clinical signs of hypernatremia, including tremors, ataxia, and seizures, usually start when serum sodium concentration exceeds 160  mEq/L. Sometimes rapid change in serum sodium concentration may be more responsible for clinical signs than the absolute change in serum sodium concentration. A clinical diagnosis may be based on history or evidence of exposure such as presence of paintballs in the vomitus or stool and presence of clinical signs, including vomiting, ataxia, tremors, and serum electrolyte changes (hypernatremia). Other causes of hypernatremia include salt (sodium chloride) toxicosis, excessive water loss caused by nephrogenic diabetes insipidus, inadequate water intake, heat stroke, and acute or chronic renal failure. Treatment objectives are decontamination, correction of electrolytes, seizure control, and supportive care. The animal should first be stabilized by controlling seizures

142

Section  II  Toxicologic Diseases

before starting decontamination or supportive care if animal is presented with CNS signs. Emesis can be induced with hydrogen peroxide or apomorphine if the exposure is within 2 hours and if no clinical signs are present. Do not give activated charcoal as it does not adsorb sorbitol or most glycols very well. Charcoal administration can also lead to development of hypernatremia in some dogs. After emesis a warm-water enema should be administered at 20  ml/kg to help move the paintballs out of the GI tract. Electrolytes are monitored; and hypernatremia is treated with 5% dextrose, 0.45% or 0.9% saline IV, or lactated Ringer’s solution with 5% dextrose. Serum sodium concentration must not be decreased faster than 0.5 to 1  mEq/L/hour since a rapid drop in serum sodium concentrations can cause water influx into the brain and cerebral edema. Other electrolytes should be corrected as needed. Seizures should be controlled with diazepam (0.5 to 2  mg/kg IV as needed). Complete recovery may occur in 24 hours or longer.

Grape and Raisin Toxicosis Etiopathogenesis The link between grape or raisin ingestion and nephrotoxicosis in dogs is relatively new. A recent report from the ASPCA Animal Poison Control Center has described the development of acute renal failure (ARF) in 43 dogs following ingestion of fresh or desiccated fruits of the Vitis spp. Although the exact nephrotoxic principle found in grapes and raisins currently remains unknown, several theories have been proposed, including the possible presence of pesticide residues, heavy metals, or various molds producing mycotoxins.

Toxicity Not all dogs ingesting grapes or raisins develop renal failure. The lowest documented grape and raisin dose associated with the development of ARF in dogs is 0.7 oz/kg and 0.11 oz/kg, respectively. A 10-kg dog ingesting 7 oz of grapes would have potential for developing ARF. However, one cannot conclude that these are in fact the lowest doses leading to ARF in dogs. In terms of exposure, one grape is equal to one raisin, although there are more raisins per unit weight. Although grape and raisin toxicosis has been most commonly described in dogs, there are unconfirmed reports of ferrets and cats developing ARF following ingestion of fruits of the Vitis spp.

Clinical Features In dogs clinical signs occur within a few hours of exposure or can be delayed for up to 24 hours. Commonly reported signs include vomiting (100%), lethargy (77%), anorexia (72%), diarrhea 51%), decreased urine output (49%), abdominal pain (28%), ataxia (23%), and weakness (23%). Clinical signs are quickly followed by characteristic changes in serum chemistry profile. Clinical chemistry changes observed within 24 hours generally include elevations in serum creatinine and

phosphorus and a higher Ca × P product. By 48 hours after exposure, the blood urea nitrogen (BUN) begins to climb; serum calcium elevations are observed approximately 48 to 72 hours later. A urinalysis may reveal presence of isosthenuria, casts, protein, and glucose. Anuria or oliguria are common sequelae in severe cases and, together with the development of neurologic signs such as ataxia and weakness, generally predict a poor prognosis. Hyperkalemia commonly accompanies oliguria and is associated with metabolic acidosis.

Pathologic Findings Acute tubular necrosis, particularly of proximal tubules, and dystrophic mineralization of soft tissue may be observed histologically.

Differential Diagnoses The differential diagnosis for raisin toxicosis includes ethylene glycol toxicity, nonsteroidal antiinflammatory drug (NSAID) toxicity, lily toxicity in cats, infectious diseases such as leptospirosis, bacterial pyelonephritis, hypoadrenocorticism (Addison’s), vitamin D/analog ingestion, and chronic renal failure.

Treatment If ingestion is less than 12 hours and the dog is asymptomatic, removal of the agent from the GI tract is the primary goal. Emesis induction followed by one to two doses of activated charcoal is recommended. In addition, if any grapes or raisins are found in the stool, an enema could be performed to further remove the agent from GI tract. Intravenous crystalloid fluid diuresis at twice the maintenance rate is recommended to prevent or minimize renal tubular damage for 48 hours or longer. Patients with decreased urine production may require the administration of a loop diuretic such as furosemide, central venous pressure and urine output monitoring, and weighing regularly. Baseline blood work evaluating renal function should be performed and repeated daily for 2 to 3 days or until the resolution of clinical signs. Monitor serum BUN, creatinine, calcium, phosphorus, electrolytes, bicarbonates, total protein, and a complete blood count. A urinalysis may show the presence of isosthenuria, casts, proteinuria, or glucosuria. Vomiting can be controlled with an antiemetic such as metoclopramide, and GI protectants such as an H2blocker (famotidine) or a proton pump inhibitor (omeprazole) and sucralfate administered. Hyperphosphatemia can be treated with phosphate binders such as aluminum hydroxide at 30 to 90  mg/kg/day. Magnesium-containing phosphate binders are to be avoided since the renal elimination of magnesium may be impaired with decreased renal function. Placing the patient on a low-protein diet may also be beneficial. If diuresis-refractory oliguria or anuria develops, peritoneal dialysis can be performed and may aid in allowing time for the regeneration of renal tubules to occur. The prognosis depends on various factors such as severity of exposure; individual susceptibility; preexposure renal

function; and, most important, how quickly the condition is recognized and therapy is instituted. Hospitalization and supportive therapy may be required for days to several weeks. Mortality rate can be high; as nearly 50% of the 43 dogs reported in a recent retrospective study died or were euthanized.

Lily toxicosis in Cats Etiopathogenesis Members of the Lilium and Hemerocallis genera are considered nephrotoxic to cats, leading to ARF. Implicated species include Easter lilies (Lilium longiflorum), tiger lilies (L. tigrinum), stargazer lilies (L. auratum), rubrum lilies (L. speciosum), Japanese show lilies (L. lancifolimu), as well as daylilies (Hemerocallis spp.). Exposure to any part of the plant, including pollen, can lead to toxicosis. Consuming less than one leaf can lead to severe toxicosis. Thus far only cats are known to develop renal failure from lilies. Although the exact mechanism of action for lily toxicity remains elusive, studies suggest that the toxin is water soluble and is more concentrated in flowers than in leaves or other parts of the plant. Not all plants containing the name lily are considered true lilies. As such, neither lily-of-the-valley (Convallaria spp.) nor the peace lily (Spathiphyllum spp.) belongs to the above-mentioned genera, but they can nevertheless be toxic by a different means. Peace lilies and calla lil ies (Zantedeschia spp.) contain insoluble calcium oxalate crystals, which can lead to oral irritation and swelling.

Clinical Findings Signs of lily toxicosis usually develop within 12 hours following exposure, although signs may develop within hours or be delayed for up to 5 days after exposure. Commonly reported signs include vomiting, anorexia, and depression, which typically occur in the hours following ingestion. BUN, creatinine, potassium, and phosphorus concentrations begin rising within 24 to 72 hours after exposure. The creatinine concentration is usually disproportionately elevated when compared to the BUN, with values as high as 53 mg/dl. A urinalysis is helpful in determining if renal tubular damage has occurred and typically reveals isosthenuria, presence of casts, protein, and glucose. Epithelial casts may be seen in the urine by 18 hours after exposure.

Differential Diagnoses The differential diagnosis of lily toxicosis in cats includes ethylene glycol toxicity, NSAID toxicity, infectious diseases such as leptospirosis, bacterial pyelonephritis, lymphosarcoma and chronic renal failure.

Treatment Renal failure may be permanent if not treated early. The therapeutic goal is to prevent renal tubular damage

Chapter  31  Recently Recognized Animal Toxicants

143

and obstruction secondary to necrosis and sloughing of epithelial cells. The most important first step is to remove plant material from the GI tract. If ingestion is less than 2 hours and the animal is asymptomatic, emesis can be induced. Emesis should be followed with one to two doses of activated charcoal (6 to 8 hours apart) with a cathartic for the first dose and without a cathartic for subsequent administrations. Baseline blood work should be obtained, especially serum BUN and creatinine. Obtaining a urinespecific gravity before treatment is also recommended. Renal function should be monitored daily for a minimum of 2 to 3 days or for as long as needed. Diuresis with lactated Ringer’s solution should be initiated at twice maintenance rate of ≈130 ml/kg/day for a minimum of 48 hours. Intravenous fluid therapy should be continued longer if symptoms persist. Placing the animal on a low-protein diet is also recommended in the presence of ARF.

Prognosis Delaying treatment by 18 to 24 hours may result in irreversible renal failure leading to death (or euthanasia) within the following few days. However, with prompt and aggressive treatment renal injury may be prevented. The prognosis is poor when anuria or oliguria develops, but renal function may be restored if peritoneal dialysis is performed. Treatment may be needed for days to weeks for complete recovery.

References and Suggested Reading Burrows GE, Tyrl RJ: Toxic plants of North America, Ames, Ia, 2001, Iowa State University Press, p 1107. DeClementi CD et al: Suspected toxicosis after topical administration of minoxidil in 2 cats, J Vet Emerg Crit Care 14:287, 2004. Donaldson C: Paintball toxicosis in dogs, Vet Med 98:995, 2003. Dunayer EK: Hypoglycemia following canine ingestion of xylitol-containing gum, Vet Hum Toxicol 46:87, 2004. Eubig PA et al: Acute renal failure in dogs subsequent to the ingestion of grapes or raisins: a retrospective evaluation of 43 dogs (1992-2002), J Vet Intern Med 19:663, 2005. Hall JO: Lily nephrotoxicity. In August JR, editor: Consultations in feline internal medicine 4, Philadelphia, 2001, Saunders, p 308. Hortman CL et al: Gastric outflow obstruction after ingestion of wood glue in a dog, J Am Anim Hosp Assoc 39:4751, 2003. Khan SA: Brunfelsia species: beautiful but deadly, Vet Med 3:138, 2008. Milewski LM, Khan SA: An overview of potentially life threatening poisonous plants in dogs and cats, J Vet Emerg Crit Care 16(1):25, 2006. Morrow CK et al: Canine renal pathology associated with grape or raisin ingestion: 10 cases, J Vet Diagn Invest 17(3):223, 2005. Spainhour Jr.CB et al: A toxicologic investigation of the garden shrub Brunfelsia calcyina var. floribunda (yesterday-today-andtomorrow) in three species, J Vet Diagn Invest 2:3, 1990. Volmer PA: Easter lily toxicosis in cats, Vet Med 94(4):331, 1999.

CHAPTER 

32

Human Drugs of Abuse Petra A. Volmer, Urbana, Illinois

A

nimal exposures to human “drugs of abuse” occur periodically in veterinary medicine. In many cases the owners are reluctant to admit that the animal was exposed until it is in severe distress. Often illicit drugs are contaminated with other compounds that may possess pharmacologic activity, causing unique combinations of clinical signs. Diagnosis of a toxicosis is often based on characteristic clinical signs and history of exposure. There has been a recent introduction of over-the-counter drug testing kits available at most pharmacies. These kits are designed for rapid determination of drug presence in urine and, although designed for in-home human use, may provide useful diagnostic information in the veterinary clinical setting. Some kits may test for as many as 12 drugs.

Amphetamines This class of compounds includes a number of prescription and illicit products, all derivatives of the parent compound amphetamine. Most animal exposures are a result of the accidental ingestion of human prescription products used for the treatment of obesity, narcolepsy, and attention-deficit hyperactivity disorder. Exposure to unlawful amphetamine compounds can also occur. Street names for amphetamine can include speed, uppers, dex or dexies, and bennies. Methamphetamine production is on the rise in clandestine laboratories in many areas of the United States. Street names for methamphetamine can include ice and glass for the clear, translucent crystals; and crystal, crank, and meth for the white or yellow powder form. Designer amphetamines include 4-methylaminorex (ice, U4EUh), methcathinone (cat), 3,4-methylenedioxy-Nmethyl-amphetamine (MDMA [ecstasy, XTC, Adam, MDA]) and 3,4-methylenedixoy-N-ethylamphetamine (MDEA [Eve]) (Volmer, 2006; Llera and Volmer, 2006) The amphetamines as a class are well absorbed orally, with peak plasma levels occurring by 1 to 3 hours; thus clinical signs can develop rapidly. Some pharmaceutical products are extended-release preparations, with the result of prolonging absorption and delaying the onset of signs. Amphetamine and its metabolites are excreted in the urine in a pH-dependent manner, with a lower pH-enhancing excretion (Baggot and Davis, 1972). Amphetamines have a stimulant effect on the cerebral cortex through release of catecholamines, acting as a dopamine excitatory receptor agonist and enhancing release of serotonin. Toxic dosages of amphetamine products are low: the oral median lethal dosage for amphetamine sulfate in the dog is 20 to 27  mg/kg; for methamphetamine hydrochloride it is 9 to 11  mg/kg (Zalis et al., 1965). Signs in field cases can be seen at dosages much lower than experimental lethal dosages. 144

Exposed animals exhibit signs associated with stimulation. Behavioral effects can include initial restlessness, pacing, panting, and an inability to sit still. These signs can progress to pronounced hyperactivity, hypersalivation, vocalization, tachypnea, tachycardia, tremors, hyperthermia, seizures, and potentially death. In some cases animals may exhibit depression, weakness, and bradycardia. Diagnosis is based on clinical signs and history of exposure. Amphetamines can be detected in urine. Over-thecounter drug testing kits may be of use in diagnosing an exposure in the acute clinical setting. Animals should be stabilized and then decontaminated. Animals with known ingestions of amphetamine products less than 30 minutes prior can undergo induction of emesis followed by administration of activated charcoal and a cathartic. Animals already exhibiting signs of stimulation such as restlessness or worse should not be induced to vomit because of the risk of aspiration. Similarly, if the product is rapidly absorbed with the possible rapid onset of signs, emesis is not recommended. For those cases gastric lavage followed by the instillation of activated charcoal and a cathartic is a safer approach. Sustained-release medications may require repeated doses of activated charcoal. Excitability, tremors, seizures, and other stimulant signs associated with amphetamine intoxication can be treated with acepromazine (0.5 to 1  mg/kg slowly intravenously [IV]; allow 15 minutes for onset of action; repeat as needed) or chlorpromazine (10 to 18  mg/kg IV repeated as needed). Phenothiazine tranquilizers have been shown to have a protective effect when used to treat amphetamine toxicoses (Catravas et al., 1977). Diazepam is not recommended because it can exacerbate the stimulatory signs in some animals. Phenobarbital, pentobarbital, and propofol may also be used to effect to prevent severe central nervous system (CNS) signs. In addition, cyproheptadine, a serotonin antagonist, may be useful to reduce the CNS signs. It has been used successfully to dampen the excessive stimulation from overexposure to antidepressant medications designed to increase serotonin in nerve synapses. Cyproheptadine is dosed at 1.1  mg/kg rectally in dogs. Tachyarrhythmias should be treated with a β-blocker such as propranolol or metoprolol. Hyperthermia should be corrected using a water mist and fans. Animals should be monitored to prevent subsequent hypothermia. The animal should be housed in a dark, quiet environment to avoid external stimulation. Intravenous fluids act to protect the kidneys and enhance elimination. Tremendous muscle stimulation

can result in rhabdomyolysis and subsequent myoglobinuria, as well as a metabolic acidosis. Urinary acidification can promote elimination of amphetamines but must not be undertaken if the animal has compromised renal function or if acidosis is already present.

Cocaine There are two main forms of cocaine: the hydrochloride salt and the pure cocaine alkaloid or freebase. The hydrochloride salt is the powdered form. It readily dissolves in water and is usually self-administered by humans either intravenously or intranasally. Some street names for cocaine powder include coke, girl, gold or star dust, snow, blow, nose candy, and white lady. Free base is the conversion of the hydrochloride form to the pure cocaine ­alkaloid. The pure alkaloid thus created exists as a flake, crystal, or rock form that vaporizes when heated, making a popping or cracking sound (i.e., crack, rock, or flake). Freebase is usually smoked but is sometimes taken orally (Volmer, 2006). Cocaine is rapidly and well absorbed from all mucosal surfaces. Inflamed or irritated surfaces may promote absorption. Cocaine is rapidly and extensively metabolized in the liver and excreted in the urine. Cocaine is a strong CNS stimulant. It acts to block the reuptake of serotonin and norepinephrine and has the ability to block cardiac sodium channels (Parker et al., 1999). The overall effect of cocaine intoxication is one of stimulation. Animals initially become restless and hyperactive. Signs can progress rapidly to tremors, tachycardia, hypotension, prolongation of QRS intervals, tachypnea, and seizures. Diagnosis is usually based on clinical signs and history of exposure. Over-the counter drug test kits may be helpful in diagnosing a cocaine toxicosis. Treatment is aimed at stabilizing the patient followed by decontamination. Because clinical signs can develop rapidly, increasing the risk of aspiration, caution should be used if inducing emesis. A safer approach may be to perform gastric lavage with administration of activated charcoal and a cathartic. Tremors and seizures can be controlled with diazepam, chlorpromazine, or a barbiturate. Pretreatment with chlorpromazine effectively antagonized the effects of cocaine in experimentally dosed dogs (Catravas amd Waters, 1981). Administration of sodium bicarbonate decreases the likelihood of development of ventricular arrhythmias, shortens the prolonged QRS complex duration, counteracts the reduction in mean arterial blood pressure, and reverses cocaineinduced sodium channel blockade (Llera and Volmer, 2006). Severe tachyarrhythmias can be treated with a β-blocker such as propranolol. Intravenous fluids should be administered to maintain renal blood flow and promote excretion. Acid-base and electrolyte status should be monitored and corrected. Hyperthermia can be severe in cocaine intoxications. Correction of body temperature can be achieved with evaporative cooling measures such as misting the animal with cool water and placing in front of a fan until normal body temperature is reached or by immersing in a tepid water bath while monitoring body temperature.

Chapter  32  Human Drugs of Abuse

145

Marijuana Tetrahydrocannabinol (THC), the major active cannabinoid in marijuana, can be found in all parts of the marijuana plant. Street names include pot, Mary Jane, MJ, weed, grass, puff, and hemp. Hashish is the dried resin from flower tops and can contain up to 10% THC. Hashish oil can contain up to 20% THC. Sinsemilla is seedless marijuana (Volmer, 2006). THC is highly lipophilic, is highly protein bound, has a large volume of distribution, and is enterohepatically recirculated. All of these characteristics result in slow elimination from the body (Otten, 2002). Only 10% to 15% of THC or its metabolites are excreted in the urine, with the remainder through the feces via the bile. Marijuana has a wide margin of safety, with a minimum oral lethal dose in the dog of greater than 3  g/kg. However, clinical signs can occur at 1000 times less than this dose (Thompson et al., 1973). Onset of clinical signs can occur within 30 to 60 minutes and can include depression, disorientation, lethargy, ataxia, bradycardia, vomiting, tremor, mydriasis, hypothermia, and urine dribbling. Analysis for THC can be performed on stomach contents and urine. Treatment is primarily symptomatic and supportive. The cannabinoids have a wide margin of safety, and toxicoses are rarely fatal. If the animal is not exhibiting any clinical signs and no other contraindications exist, emesis should be induced following an ingestion. Because enterohepatic recirculation may prolong the residence time of the cannabinoids in the body, repeated doses of activated charcoal are recommended. Body temperature should be monitored for hypothermia and corrected. In most cases recovery should occur within 24 to 72 hours.

Opioids Opium, the dried milky exudate of the poppy plant, contains 24 alkaloids, including morphine, codeine, and thebaine. The opioids are synthetic compounds that bind to the opioid receptor and are classed as agonists, partial agonists, or antagonists. They differ in their specificity and efficacy at different types of receptors. Four major opioid receptors have been identified, with most of the clinically useful opioids binding to μ (mu) receptors. Naloxone is a pure competitive antagonist with no agonist activity and has a high affinity for the μ (mu) receptor (Volmer, 2006). Most animal exposures involve ingestion of pharmaceutical preparations. The opioids are well absorbed from the gastrointestinal tract and rapidly metabolized in the liver. Morphine is glucuronidated, and the glucuronide is then excreted by the kidney. Clinical signs can include vomiting, defecation, salivation, lethargy and depression, and ataxia. In severe cases respiratory depression, constipation, hypothermia, coma and seizures, and pulmonary edema are possible. Emesis is recommended for recent ingestions in animals that are not exhibiting clinical signs. Pylorospasm produced by the opioid may cause much of the drug to remain in the stomach; thus gastric lavage, activated charcoal, and a cathartic may be effective even several hours

146

Section  II  Toxicologic Diseases

after ingestion. Respiratory depression is the most common cause of death with opioid overexposure and should be treated by establishment of a patent airway, assisted ventilation, and oxygen. Naloxone (0.01 to 0.02  mg/kg IV, intramuscularly, or subcutaneously) reverses respira­ tory depression but does not restore full consciousness. Naloxone may need to be repeated as clinical signs indicate.

Barbiturates Members in this class of compounds are all derivatives of barbituric acid. The barbiturates are used therapeutically as sedatives and anticonvulsants. Animal exposures can result from iatrogenic overdose, ingestion of illicit preparations, accidental administration of euthanasia solutions, and ingestion of euthanized carcasses. Illicit products are known as downers, reds, Christmas trees, and dolls (Volmer, 2006). The barbiturates are well absorbed orally or following intramuscular injection. Lipid solubility of the drug determines the distribution of the barbiturate in the body and the duration of effect. The barbiturates are metabolized in the liver by hepatic microsomal enzymes and excreted in the urine. Acutely the barbiturates may interfere with metabolism of other compounds by binding to hepatic P-450 enzymes, preventing them from acting on other compounds. Chronically barbiturates act to increase microsomal enzyme activity (enzyme induction), thus enhancing the biotransformation of both exogenous and some endogenous substances. Approximately 25% of phenobarbital is excreted unchanged in the urine. It can be ion trapped in the urine by urinary alkalinization, increasing excretion fivefold to tenfold (Haddad and Winchester, 1998). The efficacy of ion trapping for other barbiturates is not as distinct. Barbiturates activate γ-aminobutyric acid-a receptors and inhibit excitatory glutamate receptors. Clinical signs can include depression, ataxia, incoordination, weakness, disorientation, recumbency, coma, hypothermia, tachycardia or bradycardia, and death. Barbiturates can be detected in stomach contents, blood, urine, liver, and feces. For recent ingestions in animals exhibiting no other clinical signs, emesis followed by repeated dosages of activated charcoal and a cathartic is recommended. Activated

charcoal acts as a “sink,” encouraging the drug to diffuse back into the intestine from the circulation, even for compounds administered parenterally (Plumb, 2005). Gastric lavage followed by activated charcoal and a cathartic is a safer alternative for animals exhibiting clinical signs (and risking aspiration from induction of emesis). Death is usually the result of respiratory depression; therefore intubation, administration of oxygen, and assisted ventilation may be required. Body temperature should be monitored and corrected. Ventricular fibrillation and cardiac arrest can result from some barbiturates and be exacerbated by profound hypothermia (Haddad and Winchester, 1998). Supportive care, including intravenous fluids, is recommended. Forced alkaline diuresis may facilitate the excretion of some barbiturates, especially phenobarbital.

References and Suggested Reading Baggot JD, Davis LE: Pharmacokinetic study of amphetamine elimination in dogs and swine, Biochem Pharmacol 21:1967, 1972. Catravas JD et al: The effects of haloperidol, chlorpromazine and propranolol on acute amphetamine poisoning in the conscious dog, J Pharmacol Exp Ther 202:230, 1977. Catravas JD, Waters IW: Acute cocaine intoxication in the conscious dog: studies on the mechanism of lethality, J Pharmacol Exp Ther 217:350, 1981. Haddad LM, Winchester JF: Barbiturates. In Haddad LM, Shannon MW, Winchester JF: Clinical management of poisoning and drug overdose, ed 3, Philadelphia, 1998, Saunders, 521. Llera RM, Volmer PA: Hazards faced by police dogs used for drug detection, J Am Vet Med Assoc 228:1028, 2006. Otten EJ: Marijuana. In Goldfrank LR et al: Toxicologic emergencies, ed 7, New York, 2002, McGraw-Hill, p 1055. Parker RB et al: Comparative effects of sodium bicarbonate and sodium chloride on reversing cocaine-induced changes in the electrocardiogram, J Cardiovasc Pharmacol 34:864, 1999. Plumb DC: Phenobarbital. In Plumb DC, editor: Plumb’s veterinary drug handbook, ed 5, Ames, Ia, 2005, Blackwell Publishing, p 620. Thompson GR et al: Comparison of acute oral toxicity of cannabinoids in rats, dogs, and monkeys, Toxicol Appl Pharmacol 25:363, 1973. Volmer PA: Recreational Drugs. In Peterson M, Talcott P: Small animal toxicology, ed 2, Philadelphia, 2006, Saunders, p. 273. Zalis EG et al: Acute lethality of the amphetamines in dogs and its antagonism by curare, Proc Soc Exp Biol Med 118:557, 1965.

CHAPTER 

33

Toxicology of Veterinary and Human Estrogen and Progesterone Formulations in Dogs Margaret V. Root Kustritz, St. Paul, Minnesota

E

strogens and progestins are naturally occurring synthetic hormones that are used therapeutically for a variety of problems affecting the reproductive and other body systems. The use of these hormones can be associated with toxicosis.

Estrogens Estrogen formulations are used in small animal veterinary practice for treatment of urethral sphincter mechanism incontinence and pregnancy termination. Other uses of estrogen include estrus induction in bitches and treatment of prostate disease in dogs (although I have achieved only equivocal success with the former and do not recommend the latter). The most commonly used forms of estrogen in clinical practice are estradiol cypionate (22 to 44  mcg/kg intramuscularly for pregnancy termination) and diethylstilbestrol (DES; 1 to 5  mg once daily orally for 5 days and then every 4 to 7 days as needed for urethral sphincter mechanism incompetence). Estradiol is the most active endogenous estrogen and is typically administered parenterally. It is metabolized by the liver and eliminated mostly in the urine and to a lesser extent in bile. The half-life of injectable estradiol in humans is 4 days. DES is a synthetic nonsteroidal compound with estrogenic activity. It is usually administered orally, metabolized by the liver, and finally eliminated in urine and bile. The half-life of oral DES in humans is 3 to 4 days.

Acute Overdose/Short-Term Effects There are no reported studies describing acute toxicity of estrogens in dogs. In humans acute overdose is accompanied by nausea and vomiting. In rats toxicity studies demonstrated kidney or liver failure as the cause of death, with premonitory signs of depression, abnormal gait, and convulsions. The most serious short-term effect of estrogen administration in dogs is pancytopenia. This toxic effect of estrogen is reported to occur more commonly in older animals exposed to high doses of estrogen. However, I am unaware of studies quantifying the term high or differentiating a single exposure from chronic administration. Dogs are reported to be more sensitive to toxic effects of estrogen than humans or other animal species.

Estrogen may express a toxic effect on bone marrow directly through receptors for estradiol-1- β. The highest expression of receptors to endogenous estrogen in dogs may be present in canine bone marrow. Estrogen also may induce secretion of a myelopoiesis-inhibitory factor that suppresses replication of granulocyte and macrophage progenitor cells in the bone marrow. Clinically myeloid hyperplasia, evidenced by leukocytosis and thrombocytosis, is followed by myeloid hypoplasia, evidenced by leukopenia; thrombocytopenia; and later normocytic, normochromic, nonregenerative anemia. In a review of 51 cases of pancytopenia in dogs (Weiss, Evanson, and Sykes, 1999), two (3.9%) were caused by estrogen toxicity. Other causes of pancytopenia in that report were exposure to chemotherapeutic drugs (43.1%), parvovirus infection (9.8%), malignant histiocytosis (9.8%), sepsis (5.9%), immune-mediated hemolytic disease (5.9%), lymphoblastic leukemia (3.9%), and ehrlichiosis (3.9%). Bone marrow suppression also has been reported in dogs with estrogen-secreting tumors of the testes. Clinical signs of pancytopenia may include lethargy, pale mucous membranes, petechial or ecchymotic hemorrhages, hematuria, hemoptysis, melena, recurrent infections, and fever. Clinical signs and changes in the peripheral blood smear may not develop until up to 3 weeks after estrogen exposure. Definitive diagnosis of estrogen toxicity as a cause of pancytopenia requires knowledge of estrogen exposure. Determination of prognosis may require submission of aspirates or core biopsy specimens from the bone marrow.

Long-Term Effects Chronic administration of estrogen to bitches in diestrus is associated with increased incidence of pyometra. Exposure to estrogen during pregnancy is contraindicated since estrogen is teratogenic and may be embryotoxic. In humans prenatal exposure to DES is associated with increased incidence of vaginal and cervical clear cell adenocarcinomas and possible increased incidence of testicular neoplasia. In one canine study long-term estrogen therapy was associated with development of ovarian papillary carcinomas. Finally, exposure to estrogen causes transformation of cuboidal or columnar epithelium to squamous epithelium in the genitourinary 147

148

Section  II  Toxicologic Diseases

tract, including the renal cortex, and the thyroid gland. This squamous metaplasia is associated with secretory stasis and predisposition to prostatitis in dogs but has not been associated with changes in renal or thyroid function.

Therapy for Pancytopenia Treatment for pancytopenia includes supportive therapy with intravenous fluids and antibiotics. Transfusion of whole blood or specific blood products such as platelet-rich plasma may be required, depending on the animal’s clinical presentation. Potential sources of infectious disease should be avoided. Glucocorticoids are contraindicated in these immunosuppressed patients. It may be helpful to consult with a hematologist in difficult-to-manage patients. Resolution may occur within 30 to 40 days but may take several months. An undefined percentage of animals will die.

Progestins Progestins are used most commonly in small animal veterinary practice for estrus suppression. Other reported uses include treatment of false pregnancy in bitches and paraphimosis in neutered male dogs. Many progestins are available worldwide since elective ovariohysterectomy is not performed in many countries, leaving medical estrus suppression as the standard of care. Compounds most commonly used in the United States are megestrol acetate (Ovaban, Schering) and medroxyprogesterone acetate. Both are synthetic progestins. Only megestrol acetate is approved for use in dogs in the United States. Megestrol acetate is administered orally and is metabolized slowly by the liver, with a half-life of 8 days. For estrus suppression megestrol acetate is administered at a dose of 0.55  mg/kg once daily orally for 32 days in anestrus or at a dose of 2.2  mg/kg once daily orally for 8 days in early proestrus; note that total dosage is the same.

Acute Overdose/Short-Term Effects There are no reported studies describing acute toxicity of progestins in dogs. Short-term effects are not life threatening and are reversible on withdrawal of the drug. These changes include lethargy, polyphagia and weight gain, and altered personality.

Long-Term Effects Progestins administered chronically to dogs can induce adrenocortical atrophy and iatrogenic hypoadrenocorticism. Serum cortisol concentrations are reported to return to normal within several weeks of drug withdrawal. Progestins also may induce insulin resistance and diabetes mellitus in dogs, which may or may not reverse on withdrawal of progestin therapy. Progestins are reported to induce cystic endometrial hyperplasia and pyometra in bitches, although the manufacturer of megestrol acetate claims the prevalence of pyometra to be less than 1% when the product is administered as directed. Finally, dogs are unique in the sensitivity of their mammary tissue to neoplastic change after long-term exposure to progesterone. This effect may be

mediated by growth hormone. Experimental attempts to induce mammary neoplasia in dogs with progestin administration required very long-term exposure to high doses of the compounds used. Management of progestin toxicosis involves withdrawal of the offending hormone and treatment of any related complications (e.g., pyometra, diabetes mellitus) when possible.

Human Estrogen and Estrogen/Progestin Medications Dogs may be exposed to human hormone replacement or contraceptive preparations. Most hormone replacement therapies contain estrogen, and most contraceptives contain either progestins alone or a combination of estrogen and progesterone (Table 33-1). The ratio of estrogen to progesterone in human contraceptive preparation is such that dogs ingesting these medications tend to be overexposed to estrogen. Most human contraceptive pills or tablets contain 20 to 50  mcg of estrogen per unit. Dogs may also be exposed by ingestion of vaginal rings; skin patches; and topical creams or gels containing estrogen, progestin,

Table  33-1 Human Hormone Replacement and Contraceptive Preparations Brand Name(S) Cenestin (Duramed) Climara (Berlex) Enjuvia (Duramed) Estrace (Warner Chilcott/Bristol-Myers Squibb) Estraderm (Novartis) Estrasorb (Novavax) Estrogel (Solvay) Femring (Warner Chilcott) Premarin (Wyeth-Ayerst) Exluton (Organon) Femulen (Pharmacia) Microlut (Schering) MicroNovum (Schering) Microval (Wyeth-Ayerst) Neogest (Schering) Noregeston (Schering) Noriday (Pharmacia) NOR-QD (Watson) Ovrette (Wyeth-Ayerst) Alesse (Wyeth-Ayerst) Brevicon (Searle) Demulen (Searle) Desogen (Organon) Estrostep (Parke-Davis) Jenest (Organon) Levlen (Berlex) Levlite (Berlex) Levora (Watson) Lo/Ovral (Wyeth-Ayerst) Loestrin (Parke-Davis)

Progestin

Estrogen X X X X X X X X X

X X X X X X X X X X X X X X X X X X X X X

X X X X X X X X X X X (Continued)

Chapter  34  Herbal Hazards



Table  33-1 Human Hormone Replacement and Contraceptive Preparations—(Cont’d) Brand Name(S) Mircette (Organon) Modicon (Ortho-McNeil) Necon (Watson) Nordette (Wyeth-Ayerst) Norethin (Roberts) Norinyl (Watson) Ortho-Cept (Ortho-McNeil) Ortho-Cyclen (Ortho-McNeil) Ortho-Novum (Ortho-McNeil) Ortho-Tri-Cyclen (Ortho-McNeil) Ovcon (Bristol-Myers Squibb) Ovral (Wyeth-Ayerst) Tri-Norinyl (Watson) Triphasil (Wyeth-Ayerst) Trivora (Watson) Zovia (Watson)

Progestin

Estrogen

X X X X X X X X X X X X X X X X

X X X X X X X X X X X X X X X X

X, Present.

CHAPTER 

149

or a combination of the two. As with any intoxication, information from the owner regarding the product and amount ingested is invaluable for determination of likelihood of adverse effects. An emetic such as apomorphine may be administered if the ingestion has occurred within 30 minutes. Short- and long-term effects are as expected for the individual hormones described previously. Adverse effects and complications of long-term use of combination estrogen-progesterone therapies in humans include venous thrombosis, ischemic stroke, and heart disease. There are no reported studies evaluating such effects in dogs.

References and Suggested Reading Mahony OM: Estrogen toxicity. In: Tilley LP, Smith FWK, editors: The five-minute veterinary consult, Philadelphia, 2004, Lippincott, Williams & Wilkins, p 430. Maier WE, Herman JR: Pharmacology and toxicology of ethinyl estradiol and norethindrone acetate in experimental animals, Regul Toxicol Pharmacol 34:53, 2001. Plumb DC: Veterinary drug handbook,. Ames IA, 2005, Blackwell Publishing, pp 357, 447, 694, 697. Weiss DJ, Evanson O, Sykes J: A retrospective study of canine pancytopenia, Vet Clin Pathol 28:83, 1999.

34

Herbal Hazards Elizabeth A. Hausner, Beltsville, Maryland Robert H. Poppenga, Davis, California

T

he increased use of herbal preparations and the potential for intoxication or adverse events following their use obligate the clinician to consider these substances in cases of suspected poisonings. The incidence of animal toxicoses or adverse events following the use of natural remedies has not been specifically determined in veterinary medicine; however, it is not likely to be higher than the incidence of these effects from many conventional pharmaceuticals.

Regulations In 1994 Congress passed the Dietary Supplement and Health Education Act (DSHEA) creating a new category of substances termed dietary supplements. Dietary supplements include minerals, vitamins, amino acids, herbs,

and any product sold as a “dietary supplement” before October 15, 1994. The Food and Drug Administration (FDA) Center for Veterinary Medicine interpreted the DSHEA as not applying to substances used in animals, leaving veterinary herbals and dietary supplements regulated as foods, food additives, or new animal drugs, depending on the ingredients and their intended use. Herbal products can be marketed as dietary supplements for humans without premarket testing for safety or efficacy, and they can be manufactured without regard to quality control. Consequently variation in the concentration of active ingredient and accuracy of the herbal material used are just two of the potential problems with current herbal or natural products. These problems can alter the efficacy of or potential toxicosis from these products. In contrast, proof of safety and efficacy are required

150

Section  II  Toxicologic Diseases

by the FDA before marketing prescription and over-thecounter (OTC) drugs. In addition, their manufacture is regulated to ensure a consistent product. Of course, nothing prevents a product intended for use in or on humans from being used in or on animals.

Intoxication Scenarios Unfortunately, there is almost no information regarding the overall incidence of adverse drug reactions (ADRs) to conventional drugs or herbal remedies in veterinary medicine, and it is likely that ADRs are underreported for both. It is worth noting that in several cases the reported incidence of animal intoxication from an herb, herbal preparation, or dietary supplement seems to parallel its popularity (Ooms, Khan, and Means, 2001; GwaltneyBrant, Albretsen, and Khan, 2000). There are a number of scenarios in which animals may experience an adverse reaction to or toxicosis from an herbal preparation. 1. A preparation may contain a known toxicant. For example, the dried rootstocks of Aconitum spp. contain several constituents that are acutely cardiotoxic (Lin, Chan, and Means, 2005). Pennyroyal oil containing the putative toxin pulegone was responsible for the death of a dog after dermal application to control fleas (Sudekum et al., 1992). 2. A remedy may contain a toxicant that is not acutely toxic but may be toxic when given chronically. Pyrrolizidine alkaloids are found in many plant species and, when ingested over time, cause severe liver disease (Prakash et al., 1999; Stedman, 2002). 3. Errors may be made when preparing a remedy. For example, an anise seed preparation was contaminated with the highly toxic Conium maculatum (poison hemlock) seed (deSmet, 1991). An outbreak of renal interstitial fibrosis in women taking Chinese herbs for weight loss was attributed to the use of Aristolochia fangchi instead of Stephania tetranda in imported powdered extracts (Vanderweghem, 1998). 4. Herbal preparations can be intentionally adulterated with chemical contaminants. Many Chinese herbal patent medicines contain drugs such as nonsteroidal antiinflammatory drugs (NSAIDs) or sedatives (Ko, 1998). Also, heavy metal and pesticide contamination has been reported (Ernst, 2002b; Saper et al., 2004). Salmonellosis has been reported in humans taking rattlesnake capsules contaminated with Salmonella Arizona (Fleischman, Haake, and Lovett, 1989). 5. The active constituents in herbal preparations can interact with other concurrently administered drugs, resulting in adverse interactions. For example, buckthorn bark and berries taken chronically can increase the loss of potassium, thus potentiating the action of cardiac glycosides and antiarrhythmic agents (DerMarderosian, 2001). Potassium loss may be exacerbated by simultaneous use of thiazide diuretics, corticosteroids, and licorice root (DerMarderosian, 2001). In addition, active constituents in herbal preparations can induce liver-metabolizing enzymes,

which can alter the metabolism and kinetics of coadministered conventional drugs. For example, eucalyptus oil induces liver enzyme activity (DerMarderosian, 2001). This scenario of adverse pharmacologic interactions may occur when the owner does not inform the veterinarian of the intentional use of herbal preparations. 6. Finally, pets may consume improperly stored remedies, resulting in ingestion of a large quantity of a product. Ultimately of equal or greater concern than intoxication from herbal remedies is the potential delay in seeking treatment for otherwise treatable diseases.

Active Herbal Constituents The following broad classes of active chemical constituents occur in plants: volatile oils, resins, alkaloids, polysaccharides, phenols, glycosides, and fixed oils (Hung, Lewin, and Howland, 1998). Volatile oils are odorous plant ingredients (e.g., catnip, garlic, and citrus). Resins are complex chemical mixtures that can be strong gastrointestinal irritants. Alkaloids are a heterogeneous group of alkaline, organic, and nitrogenous compounds. Glycosides are sugar esters containing a sugar (glycol) and a nonsugar (aglycone). In some cases the glycosides are not toxic. However, hydrolysis of the glycosides after ingestion can release toxic aglycones. Fixed oils are esters of long-chain fatty acids and alcohols. Herbs containing fixed oils are often used as emollients, demulcents, and bases for other agents; in general these are the least toxic of the plant constituents. There is a misperception that preparations from plants are inherently safe and nonchemical in nature. Many plant-derived chemicals are biologically active and therefore potentially toxic. Concentrated extracts of a number of herbs have proven to be toxic even if the entire plant may be used with relative safety. Although green tea is consumed by many people with apparent safety, an extract of green tea marketed in Europe caused a significant number of adverse hepatic events, including fulminant hepatitis. The extract was withdrawn from the market (Gloro et al., 2005).

Toxicity of Specific Herbs or Other Natural Products Some of the most commonly encountered herbals are discussed in the following paragraphs; others are listed in Table 34-1.

Blue-Green Algae Blue-green (BG) algae are single-celled organisms that have been promoted for their nutritional properties. Several BG algal species produce potent toxins. Microcystis aeruginosa produces the hepatotoxic microcystins. Anabaena flosaquae produce the neurotoxins anatoxin-a and anatoxin as. Aphanizomenon flos-aquae produce the neurotoxins saxitoxin and neosaxitoxin. Efforts are underway to better define the risks associated with ingestion of potentially toxigenic BG algae and to establish safe concentrations of

Chapter  34  Herbal Hazards



151

Table  34-1 Additional Herbs of Toxicologic Concern Scientific Name

Common Names

Active Constituents

Target Organs

Acorus calamus

Acorus, calamus, sweet flag, sweet root, sweet cane, sweet cinnamon Horse chestnut, buckeye

β-Asarone (procarcinogen)

Liver: potent hepatocarcinogen

Arnica, wolf’s bane, leopard’s bane

Esculin, nicotine, quercetin, rutin, saponins, shikimic acid Sesquiterpene lactones

Gastrointestinal, nervous Skin: dermatitis

Belladonna, deadly nightshade

Atropine

Conium maculatum

Poison hemlock

Convallaria majalis Cytisus scoparius Datura stramonium

Lily-of-the-valley, mayflower, conval lily Scotch broom, broom, broom tops Jimsonweed, thorn apple

Dipteryx odorata Euonymus europaeus; E. atropurpureus Eupatorium perfoliatum; E. purpureum Heliotropium europaeum Hyoscyamus niger

Cardiovascular Nervous: nicotinic-like toxicosis Nervous: anticholinergic syndrome Hematologic: anticoagulant Cardiovascular

Pyrrolizidine alkaloids

Liver

Pyrrolizidine alkaloids Hyoscyamine, yoscine

Liver Nervous: anticholinergic syndrome

Ipomoea purga Mandragora officinarum

Tonka, tonka bean European spindle tree; wahoo, eastern burning bush Boneset, thoroughwort; joe pye weed, gravel root, queen-of-the-meadow Heliotrope Henbane, fetid nightshade, poison tobacco, insane root, stinky nightshade Jalap Mandrake

Coniine, other similar alkaloids Cardiac glycosides l-sparteine Atropine, scopolamine, hyoscyamine Coumarin Cardiac glycosides

Nervous: anticholinergic syndrome Nervous: nicotine-like toxicosis

Convolvulin Scopolamine, hyoscyamine

Podophyllum peltatum Sanguinaris canadensis Solanum dulcamara, other Solanum spp. Tussilago farfara Vinca major and V. minor

Mayapple, mandrake Bloodroot, red puccoon, red root Woody, bittersweet, or climbing nightshade Coltsfoot Common periwinkle, periwinkle

Podophyllin Berberine Numerous glycoalkaloids including solanine and chaconine PA alkaloid, senkirkine Vincamine

Gastrointestinal Nervous: anticholinergic syndrome Gastrointestinal: gastroenteritis Gastrointestinal Gastrointestinal, nervous, cardiovascular Liver Immune system

Aesculus hippocasteranum Arnica montana and A. latifolia Atropa belladonna

total microcystins in marketed products. Spirulina has also been promoted as a nutritional supplement and is not considered a toxigenic BG algae genus. However, some products have been found to be contaminated with mercury. Microbial contamination could possibly be a concern if harvested algae grow in water contaminated with human or animal wastes.

Ephedra or Ma Huang The dried young branches of ephedra (Ephedra spp.) have been used for their stimulating and vasoactive effects. In addition, ephedra has been used in several products promoted for weight loss. The plant constituents responsible for biologic activity are the sympathomimetic alkaloids ephedrine and pseudoephedrine. A case series involving intoxication of dogs following ingestion of a weight-loss product containing guarana (caffeine) and ma huang (ephedrine) was recently reported (Ooms, Khan, and Means, 2001). Estimated doses of the respective plants associated with adverse effects were 4.4 to 296.2  mg/kg for guarana and 1.3 to 88.9  mg/kg for ma huang. Symptomatology included hyperactivity, tremors, seizures, behavioral changes, emesis, tachycardia, and

hyperthermia. Ingestion was associated with mortality in 17% of the cases. North American species of ephedra (also called Mormon tea) have not been shown to contain the sympathomimetic alkaloids. Citrus aurantium (“bitter orange” or “Seville orange”) has appeared in many products labeled as “ephedrinefree” and is also combined with caffeine and/or guarana. The primary active components of C. aurantium are synephrine (structurally similar to epinephrine), octopamine (structurally similar to norepinephrine), and N-methyltyramine. The overall effect is that of stimulation (Fugh-Berman and Myers, 2004). Studies in humans have shown that bitter orange–containing preparations cause tachycardia and increases in systolic and diastolic pressure (Halle, Benowitz, and Jacob, 2005). Signs of intoxication can be expected to be similar to those seen with ephedra.

Guarana Guarana is the dried paste made from the crushed seeds of Paullinia cupana or P. sorbilis, a fast-growing shrub native to South America. The primary active component in the plant is caffeine, with concentrations that range from

152

Section  II  Toxicologic Diseases

3% to 5%, which compares to 1% to 2% for coffee beans. Currently the most common forms of guarana include syrups, extracts, and distillates used as flavoring agents and as a source of caffeine for the soft-drink industry. More recently it has been added to weight-loss formulations in combination with ephedra. Oral lethal doses of caffeine in dogs and cats range from 110 to 200  mg/kg of body weight and 80 to 150  mg/kg of body weight, respectively (Carson, 2001). See Ephedra earlier in the chapter for a discussion of a case series involving dogs ingesting a product containing guarana and ephedra (Ooms, Khan, and Means, 2001).

White Willow The active constituents in willow (Salix spp.) include salicylates (primarily in the form of glycosides salicortin and salicin) and tannins. Current indications for plant use include for fever and rheumatism and as an antiinflammatory. Both therapeutic and adverse effects occur through inhibition of prostaglandin synthesis. In addition, salicylates inhibit oxidative phosphorylation and Krebs cycle enzymes. In cats acetylsalicylic (AS) acid is toxic at 80 to 120  mg/kg given orally for 10 to 12 days. In dogs AS at 50  mg/kg given orally twice a day is associated with emesis; higher doses can cause depression, anorexia, diarrhea, bloody stool, melena, and metabolic acidosis. A dose of 100 to 300  mg/kg orally once daily for 1 to 4 weeks is associated with gastric ulceration; more prolonged dosing is potentially fatal (Osweiler, 1996). Cats are particularly vulnerable to overdose because of an inability to rapidly metabolize salicylates. A number of other plants contain salicylates, including Betula spp. (birch), Filipendula ulmaria (meadowsweet), and Populus spp. See Oil of Wintergreen later in the chapter.

Essential Oils Essential oils are the volatile, organic constituents of fragrant plant matter and contribute to plant fragrance and taste. They are extracted from plant material by distillation or cold-pressing. A number of essential oils are not recommended for use (e.g., aromatherapy, dermal or oral use) because of their toxicity or potential for toxicity (Tisserand and Balacs, 1999). They are listed in Table 34-2. These oils have unknown or oral LD50 values in animals of 1  g/kg or less. Most toxicity information has been derived using laboratory rodents or mice. Such data should only be used as a rough guide since they cannot always be extrapolated to other species. Essential oil safety: a guide for health care professionals is an excellent reference for in-depth discussions of general and specific essential oil toxicity. The following essential oils are of particular concern.

Camphor Camphor is an aromatic, volatile, terpene ketone derived from the wood of Cinnamomum camphora or synthesized from turpentine. Camphor oil is separated into four distinct fractions: white, brown, yellow, and blue camphor (Tisserand and Balacs, 1999). White camphor is the form used in aromatherapy and in OTC products (brown and yellow fractions contain the carcinogen safrole and are not normally available). OTC products vary in form and camphor content; external products contain 10% to 20% in semisolid forms or 1% to 10% in camphor spirits. It is used as a topical rubefacient and antipruritic agent. Camphor is rapidly absorbed from the skin and gastrointestinal tract, and toxic effects can occur within minutes of exposure. In humans signs of intoxication include emesis, abdominal distress, excitement, tremors, and ­ seizures followed by central nervous system (CNS)

Table  34-2 Most Toxic Essential Oils Oil

Genus/Species

Boldo leaf Wormseed Mustard Armoise Pennyroyal (Eur.) Tansy Thuja Calamus Wormwood Bitter Almond

Peumus boldus Chenopodium ambrosioides Brassica nigra Artemisia herba-alba Mentha pulegium Tnacetum vulgare Thuja occidentalis Acorus calamus var angustatus Artemesia absinthium Prunus amygdalus var amara Artemisia arborescens Barosma betulina; B. crenulata Cochlearia armoracia Artemiesia afra Hedeoma pulegoides Artemesia abrotanum Thuja plicata

Buchu Horseradish Lanyana Pennyroyal (N. Am.) Southernwood Western red cedar

Data from Tisserand R and Balacs T, 1999.

Oral LD50 (g/kg)

Toxic Component (%)

0.13 0.25 0.34 0.37 0.40 0.73 0.83 0.84 0.96 0.96 ? ? ? ? ? ? ?

Ascaridole: 16 Ascaridole: 60-80 Allyl isothiocyanate: 99 Thujone: 35 Pulegone: 55-95 Thujone: 66-81 Thujone: 30-80 Asarone: 45-80 Thujone: 34-71 Prussic acid: 3 Iso-thujone: 30-45 Pulegone: 50 Allyl isocyanate: 50 Thujone: 4-66 Pulegone: 60-80 Thujone: ## Thujone: 85

­ epression characterized by apnea and coma. Fatalities d have occurred in humans ingesting 1 to 2  g of camphorcontaining products, although the adult human lethal dose has been reported to be 5 to 20  g (Tisserand and Balacs, 1999; Emery and Corban, 1999). A 1-tsp amount of camphorated oil (≈1  ml of camphor) was lethal to 16-month-old and 19-month-old children.

Citrus Oil Citrus oil and citrus oil constituents such as D-limonene and linalool have been shown to have insecticidal activity. Although D-limonene has been used safely as an insecticide on dogs and cats, some citrus oil formulations or use of pure citrus oil may pose a poisoning hazard (Powers et al., 1988). Fatal adverse reactions have been reported in cats following the use of an “organic” citrus oil dip (Hooser, Beasley, and Everitt, 1986). Hypersalivation, muscle tremors, ataxia, lateral recumbency, coma, and death were noted experimentally in three cats following use of the dip according to label directions.

Melaleuca Oil Melaleuca is derived from the leaves of the Australian tea tree (Melaleuca alternifolia); it is often referred to as tea tree oil. The oil contains terpenes, sesquiterpenes, and hydrocarbons. A variety of commercially available products contain the oil; shampoos and the pure oil have been sold for use on dogs, cats, ferrets, and horses. Tea tree oil toxicosis has been reported in dogs and cats (Villar et al., 1994; Bischoff and Guale, 1998). A recent case report describes the illness of three cats exposed dermally to pure melaleuca oil for flea control (Bischoff and Guale, 1998). Clinical signs in one or more of the cats included hypothermia, ataxia, dehydration, nervousness, trembling, and coma. There were moderate increases in serum alanine aminotransferase and aspartate aminotransferase concentrations. Two cats recovered within 48 hours following decontamination and supportive care. However, one cat died ≈3 days after exposure. The primary constituent of the oil, terpinen4-ol, was detected in the urine of the cats. Another case involved the dermal application of 7 to 8 drops of oil along the backs of two dogs as a flea repellent (Kaluzienski, 2000). Within ≈12 hours one dog developed partial paralysis of the hind limbs, ataxia, and depression. The other dog only displayed depression. Decontamination (bathing) and symptomatic and supportive care resulted in rapid recovery within 24 hours.

Pennyroyal Oil This volatile oil is derived from Mentha pulegium and Hedeoma pulegoides. Pennyroyal oil has a long history of use as a flea repellent. There is one case report of pennyroyal oil toxicosis in the veterinary literature in which a dog was dermally exposed to pennyroyal oil at ≈2 g/kg (Sudekum et al., 1992). Within 1 hour of application, the dog became listless, and within 2 hours it began vomiting. Thirty hours after exposure the dog exhibited diarrhea, hemoptysis, and epistaxis. Soon thereafter it developed

Chapter  34  Herbal Hazards

153

seizures and died. Histopathologic examination of liver tissue showed massive hepatocellular necrosis.

Oil of Wintergreen Wintergreen oil is derived from Gaultheria procumbens. The oil contains a glycoside that, when hydrolyzed, releases methyl salicylate. The oil is readily absorbed through skin and is used to treat muscle aches and pains. Salicylates are toxic to dogs and cats. Since cats metabolize salicylates much more slowly than other species, they are more likely to be overdosed. Intoxicated cats may present with depression, anorexia, emesis, gastric hemorrhage, toxic hepatitis, anemia, bone marrow hypoplasia, hypernea, and hyperpyrexia (see Willow earlier in the chapter).

Product Adulteration There is a long history of Chinese patent medicines being adulterated with metals and conventional pharmaceuticals or containing natural toxins (Ko, 1998; Au et al., 2000; Ernst, 2002a; Dolan et al., 2003). Sedatives, stimulants, and NSAIDs are common pharmaceuticals added to patent medicines with no labeling to indicate their presence. Commonly found natural toxins in Chinese patent medicines include borneol (reduced camphor), aconite, toad secretions (Bufo spp., Ch’an Su), mylabris, scorpionderived toxins, borax, Acorus, and strychnine (Strychnos nux-vomica) (Ko, 1998). Chinese patent medicines often contain cinnabar (mercuric sulfide), realgar (arsenic sulfide), or litharge (lead oxide) as part of the traditional formula. Recently dietary supplements purchased largely from retail stores were tested for arsenic, cadmium, lead, and mercury (Dolan et al., 2003). Eighty-four of the 95 products tested contained botanicals as a major component of the formulation. Eleven of the 95 products contained lead at concentrations that would have caused lead intake to exceed recommended maximum levels in children and pregnant women had the products been used according to label directions. Serious adverse health effects have been documented in humans using adulterated Chinese herbal medicines (Ernst, 2002a). There are no published cases in the veterinary literature, although we are aware of one case in which a small dog ingested a number of herbal tea “balls” that were prescribed to its owner for arthritis. The dog presented to a veterinary clinic in acute renal failure several days after the ingestion. Analysis of the formulation revealed low-level heavy metal contamination (mercury and lead) and large concentrations of caffeine and the NSAID indomethacin. The acute renal failure was most likely to the result of NSAID-induced renal damage.

Drug-Herb Interactions Drug-herb interactions refer to the possibility that an herbal constituent may alter the pharmacologic effects of a conventional drug given concurrently or vice versa. The result may be either enhanced or diminished drug or herb effects or the appearance of a new effect that is not anticipated from the use of the drug or herb alone.

154

Section  II  Toxicologic Diseases

Possible interactions include those that alter the absorption, metabolism, distribution, and/or elimination of a drug or herbal constituent and result in an increase or decrease in the concentration of active agent at the site of action. For example, herbs that contain dietary fiber, mucilage, or tannins might alter the absorption of another drug or herbal constituent. Herbs containing constituents that induce liver enzymes might be expected to affect drug metabolism and/or elimination (Blumenthal, 2000). Induction of live metabolizing enzymes can increase the toxicity of drugs and other chemicals via increased production of reactive metabolites. The production of more toxic reactive metabolites is termed bioactivation (Zhou et al., 2004). Alternatively enhanced detoxification of drugs and other chemicals can decrease their toxicity or their therapeutic efficacy. Long-term use of herbs and other dietary supplements can induce enzymes associated with procarcinogen activation, thus increasing the risk of some cancers (Ryu and Chung, 2003; Zhou et al., 2004). The displacement of one drug from protein-binding sites by another agent increases the concentration of unbound drug available to target tissues. Pharmacodynamic interactions or interactions at receptor sites can be agonistic or antagonistic.

Diagnosis of Herbal Intoxication Because of the nonspecific signs associated with most intoxications, the diagnosis of a causative agent is extremely difficult without a history of exposure or administration. Such information may not be forthcoming from clients since they may not equate use of an alternative therapy with conventional drug use and therefore may not volunteer such information when queried about prior medication history. Also, clients may not volunteer such information because of embarrassment or belief that the veterinarian will not approve of such therapy. Therefore it is important to specifically question clients regarding use of natural products. An added complication is that, even with a history of exposure and a product package, the animal may have been exposed to adulterating or contaminating agents that are not listed on the package label. Clinical pathologic or postmortem findings are rarely specific for intoxication from natural products but will assist in determining affected organ systems and thus will help formulate a differential list. It may be possible to detect specific herbal constituents in biologic specimens. For example, pulegone was detected in tissues from a dog intoxicated by pennyroyal oil (Sudekum et al., 1992). Currently however, analyses for organic natural products

Table  34-3 Drug Dosages for Treatment of Intoxications Agent

Indication

Dosage

Activated charcoal

Adsorption of toxins

Syrup of ipecac

Emesis

3% hydrogen peroxide Apomorphine

Emesis Emesis

Sodium bicarbonate Digoxin Fab fragments

Urine alkalinization Cardiac glycosides (plants such as Digitalis, Nerium spp. and Bufo spp. toads)

Cimetidine Sucralfate

Gastric protection (H2 blocker) Gastrointestinal protection

Omeprazole

Treatment and prevention of ulcers Antiseizure

Loading dose of 1-2  g/kg. If multiple doses are given, follow with 0.25-0.5  g/kg q1-6h. Some preparations of activated charcoal contain a cathartic. Dogs: 1-2  ml/kg PO Cats: 3.3  ml/kg PO diluted 50:50 with water 1-2  ml/kg PO; if emesis does not occur, may repeat once more Do not use in cats. Dogs: 0.03  mg/kg IV or 0.04  mg/kg IM May also place 0.25- to 1.6-mg tablet in the conjunctival sac and dissolve with an ophthalmic irrigating solution. When emesis begins, thoroughly flush remaining material from the sac. 1 to 2  mEq/kg administered q3-4h to achieve a urine pH of 7.0 or greater Dosing is empiric. In humans it is suggested that 1.7  ml (of Digibind) be administered IV per milliliter of digoxin ingested. If dose is unknown, then 400  mg Digibind is given IV. Digibind is given over 30 minutes unless cardiac arrest is imminent, in which case a bolus is given. Monitor for anaphylaxis and hypokalemia. 5-10  mg/kg IV or PO q8h Small dogs: 0.5  g q8h Large dogs: 1  g q8h Cats: not recommended Dogs: 20  mg/dog q24h (or 0.7  mg/kg, q24h, PO)† Dogs: 0.5-2  mg/kg IV or 1  mg/kg rectally2 Cats: 0.5  mg/kg IV or 1  mg/kg rectally Loading dose of 1-2  mg/kg IV followed by maintenance IV drip of 40-60  mg/kg/min infusion rate to effect Should not be used in cats* 0.1-0.3  mg/kg TID Dogs: 2-5  mcg/kg q6-8h, PO

Diazepam Lidocaine

Premature ventricular contractions

Metoprolol Misoprostol

Tachyarrhythmias GI protection

Data from Poppenga, 2004 unless otherwise noted. GI, Gastrointestinal; IM, intramuscularly; IV, intravenously; PO, Orally. *Carson, 2001. † From Papich MG: Saunders handbook of veterinary drugs, Philadelphia, 2002, Saunders, pp 352, 376.

in tissues are not widely available, although analytic methods may improve as their use continues to increase.

Treatment of Herbal Intoxication The adage “treat the patient and not the poison” is appropriate in most suspected poisonings caused by herbal preparations. Treatment consists of decontamination followed by general supportive care. Indications and contraindications for decontamination procedures should be followed (Poppenga, 2004). Inducing emesis is contraindicated when there is high risk of aspiration (the patient is unconscious or there is neurologic depression) or the patient is having or is likely to have a seizure. Generally dermal preparations can be removed by washing with a mild soap or detergent. Care should be exercised that the personnel performing this do not themselves become contaminated. Gloves, aprons, and good ventilation are necessary. It is also important to avoid hypothermia in the patient. Supportive care is based on the clinical signs exhibited by the patient. Body temperature, status of the major organ systems, hydration, acid-base balance, urine output, neurologic status, and cardiac function require regular monitoring and evaluation. In rare cases an antidote might be available (e.g., digoxin Fab fragments for cardiac glycosides). There are also specific considerations for several botanical agents. Intoxication with salicylates frequently results in acidosis. Urinary alkalinization using sodium bicarbonate may increase the elimination by trapping the ionized salicylate molecules in the urine. It is also important to protect the gastrointestinal tract against the ulcerogenic potential of the salicylates. Treatment may include a protectant such as sucralfate, a histamine H2-receptor antagonist (cimetidine, ranitidine or famotidine), a proton pump inhibitor (omeprazole), and misoprostol (a PGE1 analog). In cases of poisoning from caffeine/guarana, ephedra, Citrus aurantium, and other materials causing CNS ­stimulation, the animal should be monitored for hyperthermia, dehydration, acidosis, cardiac arrhythmias, and seizures. Along with decontamination, fluid therapy increases urinary excretion and helps to correct electrolyte imbalances. Frequent premature ventricular contractions should be treated with lidocaine (without epinephrine). Tachyarrhythmias may require the use of a β-blocker. It must be remembered that β-blockers may also mask the early signs of shock. Drug dosages are summarized in Table 34-3.

References and Suggested Reading Au AM et al: Screening methods for drugs and heavy metals in Chinese patent medicines, Bull Environ Contam Toxicol 65:112, 2000. Bent S et al: The relative safety of ephedra compared to other herbal products, Ann Intern Med 138(6):468, 2003. Birdsall TC: 5-hyrdoxytryptophan: a clinically effective serotonin precursor, Altern Med Rev 3:271, 1998. Bischoff K, Guale F: Australian tea tree (Melaleuca alternifolia) oil poisoning in three purebred cats, J Vet Diagn Invest 10:208, 1998.

Chapter  34  Herbal Hazards

155

Blumenthal M: Interactions between herbs and conventional drugs: introductory considerations, Herbal Gram 49:52, 2000. Carson TL: Methylxanthines. In Peterson ME, Talcott PA, editors: Small animal toxicology, Philadelphia, 2001, Saunders, p 563. DerMarderosian A, editor: Review of natural products, St Louis, 2001, Facts and Comparisons. DeSmet PAGM: Toxicological outlook on the quality assurance of herbal remedies In De Smet PAGM et al, editors: Adverse effects of herbal drugs 1, Berlin, 1991, Springer-Verlag, p 1. Dolan SP et al: Analysis of dietary supplements for arsenic, cadmium, mercury, and lead using inductively coupled plasma mass spectrometry, J Agric Food Chem 51:1307, 2003. Emery DP, Corban JG: Camphor toxicity, J Paediatr Child Health 35:105, 1999. Ernst E: Adulteration of Chinese herbal medicines with synthetic drugs: a systematic review, J Intern Med 252:107, 2002a. Ernst E: Toxic heavy metals and undeclared drugs in Asian herbal medicines, Trends Pharmacol Sci 23(3):136, 2002b. Fleischman S, Haake DA, Lovett MA: Salmonella Arizona infections associated with ingestion of rattlesnake capsules, Arch Intern Med 149:705, 1989. Fugh-Berman A, Ernst E: Herb-drug interactions: a review and assessment of report reliability, J Clin Pharmacol 52:587, 2001. Fugh-Berman A, Myers A: Citrus aurantium, an ingredient of dietary supplements marketed for weight loss: current status of clinical and basic research, Exp Biol Med 229:698, 2004. Gloro R et al: Fulminant hepatitis during self-medication with hydroalcoholic extract of green tea, Eur J Gastroeterol Hepatol 17:1135, 2005. Grande GA, Dannewitz SR: Symptomatic sassafras oil ingestion, Vet Hum Toxicol 29:447, 1987. Gwaltney-Brant SM, Albretsen JC, Khan SA: 5-Hydroxytryptophan toxicosis in dogs: 21 cases (1989-1999), J Am Vet Med Assoc 216:1937, 2000. Haller CA et al: An evaluation of selected herbal reference texts and comparison to published reports of adverse herbal events, Adverse Drug React Toxicol Rev 21(3):143, 2002. Haller CA, Benowitz NL, Jacob PIII: Hemodynamic effects of ephedra-free weight-loss supplements in humans, Am J Med 118(9):998, 2005. Hooser SB, Beasley VR, Everitt JI: Effects of an insecticidal dip containing D-limonene in the cat, J Am Vet Med Assoc 189:905, 1986. Hung OL, Lewin NA, Howland MA: Herbal preparations. In Goldfrank LR et al,editors: Goldfrank’s toxicologic emergencies, ed 6, Stamford, Ct, 1998, Appelton and Lange, p 1221. Kaluzienski M: Partial paralysis and altered behavior in dogs treated with melaleuca oil J Toxicol Clin Toxicol 38:518, 2000 Ko RJ: Herbal products information. In Poisoning and toxicology compendium, Cleveland, 1998, Lexi-Comp, p 834. Lazarou J, Pomeranz BH, Corey PN: Incidence of adverse drug reactions in hospitalized patients: a meta-analysis of prospective studies, JAMA 279(15):1200, 1998. Lin CC, Chan TYK, Deng JF: Clinical features and management of herb-induced aconitine poisoning, Ann Emerg Med 43:574, 2005. Ooms TG, Khan SA, Means C: Suspected caffeine and ephedrine toxicosis resulting from ingestion of an herbal supplement containing guarana and ma huang in dogs: 47 cases (19971999), J Am Vet Med Assoc 218:225, 2001. Osweiler GD: Over-the-counter drugs and illicit drugs of abuse. In The national veterinary medical series: toxicology, Philadelphia, Williams & Wilkins, pp 303, 1996. Pirmohamed M et al: Adverse drug reactions as a cause of admission to hospital: prospective analysis of 18 820 patients, Br Med J 329:15, 2004. Poppenga R: Treatment. In Plumlee KH, editor: Clinical veterinary toxicology, St. Louis, 2004, Mosby, p 13.

156

Section  II  Toxicologic Diseases

Powers KA et al: An evaluation of the acute toxicity of an insecticidal spray containing linalool, d-limonene, and piperonyl butoxide applied topically to domestic cats, Vet Hum Toxicol 30(3):206, 1988. Prakash AS et al: Pyrrolizidine alkaloids in human diet, Mutat Res 443:53, 1999. Ryu S, Chung W: Induction of the procarcinogen-activating CYP1A2 by a herbal dietary supplement in rats and humans, Food Cosmet Toxicol 41:861, 2003. Saper RB et al: Heavy metal content of ayurvedic herbal medicine products, JAMA 292(23):2868, 2004. Segelman AB et al: Sassafras and herb tea: potential health hazards, JAMA 236:477, 1976. Stedman C: Herbal hepatotoxicity, Semin Liver Dis 22(2): 195206, 2002. Sudekum M et al: Pennyroyal oil toxicosis in a dog, J Am Vet Med Assoc 200:817, 1992.

CHAPTER 

Tisserand R, Balacs T: Essential oil safety: a guide for health care professionals, Edinburgh, UK, 1999, Churchill Livingstone. Vanherweghem LJ: Misuse of herbal remedies: the case of an outbreak of terminal renal failure in Belgium (Chinese herbs nephropathy), J Altern Complement Med 4:9, 1998. Villar D et al: Toxicity of melaleuca oil and related essential oils applied topically on dogs and cats, Vet Hum Toxicol 36:139, 1994. Yang S, Dennehy CE, Tsourournis C: Characterizing adverse events reported to the California poison control system on herbal remedies and dietary supplements: a pilot study, J Herb Pharmacother 2(3):1, 2003. Zhou S et al: Herbal bioactivation: the good, the bad and the ugly, Life Sci 74:935, 2004.

35

Aflatoxicosis in Dogs Karyn Bischoff, Ithaca, New York Tam Garland, Washington, DC

A

flatoxicosis in dogs was first described as hepatitis X in 1952. The disease was experimentally reproduced in 1955 using contaminated feed and again in 1966 using purified aflatoxin B1. Moldy corn poisoning of swine and turkey X disease were reported in the 1940s. Turkey X disease was linked to aflatoxin in 1961. Aflatoxins are a group of related compounds produced as secondary metabolites of various fungi, including Aspergillus parasiticus, A. flavus, A. nomius, and some Penicillium spp. Aflatoxins are not produced by all strains of these fungi. The most common aflatoxins in grains are named, in part, for their fluorescent color: aflatoxins B1 and B2, fluoresce blue; and aflatoxins G1 and G2, fluoresce green. Aflatoxin B1 is the most common and most toxicologically potent of the aflatoxins. High-energy agricultural crops are most often affected. Corn, peanuts, and cottonseed are frequently implicated; but rice, wheat, oats, sweet potatoes, potatoes, barley, ­millet, sesame, sorghum, cacao beans, almonds, soy, coconut, safflower, sunflower, palm kernel, cassava, cowpeas, peas, and various spices have been affected. Mold may grow on crops in the field or during storage. Factors that influence mold growth include temperature, humidity, drought stress, insect damage, and handling techniques.

Ingestion of homemade pet foods, moldy garbage, and improperly stored dog foods all have been implicated in aflatoxicosis. Commercial grain is screened routinely for aflatoxins, but sampling error has been implicated in contamination of commercial dog food. Uneven distribution of mold growth within the grain (by analogy, one moldy orange in a large bag of fruit or blue veins in a block of blue cheese) increases the risk of sampling error. A simple black light at 366 nm induces fluorescence of kojic acid—a chemical also produced by many aflatoxin-producing fungi. Kojic acid fluoresces blue-green. Its presence neither confirms nor eliminates the presence of aflatoxins. More sensitive analyses use enzyme-linked immunosorbent assays, highperformance liquid chromatography (HPLC), and liquid chromatography/mass spectrometry. HPLC is both more sensitive and more specific. Many pet food companies currently sample each lot of grain before using it in food production and then sample batches of pet food after production to minimize the problem of sampling error.

Toxicity Dogs and cats are considered very sensitive to aflatoxin (Newbern and Butler, 1969). The oral median lethal dose

(LD50) for aflatoxins in dogs has ranged from 0.5 to 1.8  mg/kg. It has been difficult to determine the total dose of aflatoxin received in field cases when the amount ingested and period of exposure may not be available. Although dog foods containing as low as 60 ppb of aflatoxin have been implicated in aflatoxicosis cases, it is rarely possible to know the actual aflatoxin exposure from food consumed before presentation. The experimental oral LD50 for aflatoxin in cats is 0.55 mg/kg. No clinical cases of aflatoxicosis have been reported in cats. Factors such as dose received, genetic predisposition, and concurrent disease may influence the course of aflatoxin poisoning. Generally younger animals, particularly males, may be more susceptible. Aflatoxin-related deaths in pups sucking a clinically healthy dam have been reported (Garland and Reagor, 2007). Pregnant and whelping bitches may be more susceptible to aflatoxicosis. Early castration decreases mortality in males of some species (Meerdink, 2004). Low dietary protein may enhance hepatocyte damage, whereas nutritional antioxidants, vitamin A, and carotene may decrease it.

Toxicokinetics Aflatoxins are highly lipophilic and are absorbed rapidly and almost completely in the duodenum. Aflatoxins enter the portal circulation and are highly protein bound in blood. The unbound fraction is distributed to the tissues, with the highest concentration occurring in the liver. The liver is the primary metabolic site for aflatoxins. Sites of secondary metabolic interest include the liver, kidneys, and small intestine. Phase I metabolism of aflatoxin B1 by cytochrome P-450 enzymes produces the reactive intermediate aflatoxin B1 8,9-epoxide. Some aflatoxin B1 is metabolized to aflatoxin M. During phase II metabolism aflatoxin B1 8,9-epoxide is conjugated to glutathione in a reaction catalyzed by glutathione S-transferase. Metabolites of aflatoxin are excreted in both urine and bile. Dogs excrete primarily aflatoxin M1 in the urine. More than 90% of aflatoxin metabolites are excreted in the urine within the first 12 hours after dosing in the dog, and urine aflatoxin is below detectable levels within 48 hours. Conjugated aflatoxin is excreted predominantly in the bile. Approximately 1% of a dose of aflatoxin is excreted as aflatoxin M1 in the milk in dairy cattle.

Mechanism of Action Phase I metabolism of aflatoxin B1 produces the highly reactive electrophile aflatoxin B1 8,9-epoxide, which binds readily to other molecules within the cell, including nucleic acids, proteins, and other constituents of subcellular organelles. Formation of deoxyribonucleic acid (DNA) adducts modifies the DNA template; thus binding of DNA polymerase may be altered, which in turn affects cellular replication. Binding to ribosomal translocase affects protein production. These changes may lead to necrosis of hepatocytes and other metabolically active cells such as renal tubular epithelium. Coagulopathy may result from decreased prothrombin and fibrinogen production. Excretion kinetics of adducts is slower than the parent compound and the aforementioned metabolites.

Chapter  35  Aflatoxicosis in Dogs

157

Aflatoxin is a known carcinogen in rats, ferrets, ducks, trout, swine, sheep, and rats. It is not known to be carcinogenic in dogs. Aflatoxins are classified by the International Agency for Research on Cancer as class I human carcinogens. Hepatocellular carcinoma has been associated with chronic aflatoxin exposure and concurrent infection with hepatitis B virus.

Clinical Signs Although aflatoxicosis is usually caused by prolonged exposure to contaminated feed, the presentation in small animals is usually acute. Dogs in recent cases involving contaminated commercial dog foods may have been ingesting the foods for weeks or months before becoming clinically ill. For example, adulterated pet food may have entered the market in October, but the first reported cases were not observed until December. Some dogs did not become symptomatic until up to 3 weeks after the diet was changed. Clinical signs of aflatoxicosis in dogs usually occur within a few days of death but may be protracted for up to 2 weeks. If the concentration of aflatoxin is very high, this is usual; but animals can, and do, survive when the concentration is low or exposure is limited. Experimentally poisoned cats that died of aflatoxicosis survived only a few days after the onset of clinical signs. Conversely, some cats have been known to survive after clinical signs of aflatoxicosis following exposure to adulterated food. The most commonly reported early clinical signs of aflatoxicosis in dogs include feed refusal or anorexia, weakness and obtundation, vomiting, and diarrhea. A few animals may die unexpectedly without showing clinical signs. Later in the course of the disease, dogs become icteric. Bilirubinuria was prominent in recent cases. Evidence of coagulopathy may include melena or frank blood in the feces, hematemesis, petechial hemorrhages, and epistaxis.

Diagnosis The primary differential diagnosis for dogs in recent food contamination–related cases of aflatoxicosis was leptospirosis, as was reported by Stenske and colleagues (2006). Other differential diagnoses that have been considered include parvovirus and anticoagulant rodenticide toxicosis based on the severe gastrointestinal hemorrhage and a variety of hepatotoxic agents, including acetaminophen; microcystin from cyanobacteria; amanitine from mushrooms; and toxins associated with cycad palms, phosphine, and iron. Diagnosis of aflatoxicosis is often based on history, clinical signs, clinical pathology findings and postmortem changes. Laboratory testing of dog food or other implicated material may be helpful in confirming the diagnosis, but sometimes this material is no longer available. Often all of the contaminated food has been consumed by the time the animal presents to the veterinarian. During a recent dog food contamination incident, three groups of dogs with similar dietary histories and clinical signs were identified by a veterinarian. Dog food was submitted to the laboratory from each of the three households, but

158

Section  II  Toxicologic Diseases

only one sample contained aflatoxin in toxicologically significant concentrations. If the dog food bags or codes from the bags are maintained, it is possible to learn what lot of food may have been contaminated. Some laboratories test for aflatoxin M1 in the urine, but urinary excretion is very rapid in dogs. There has been some success with testing serum or liver for aflatoxin, but, again because of the rapid metabolism and excretion of aflatoxin, we have found these tests to be of limited usefulness.

Clinical Chemistry Complete blood count, serum chemistry, including bile acids, and urinalysis have been recommended to support the diagnosis of aflatoxin poisoning and rule out other causes of liver failure. Total bilirubin is increased in aflatoxicosis. Changes in hepatic enzyme concentrations are variable. Serum alanine aminotransferase was elevated consistently in one report and may increase progressively (Garland and Reagor, 2007). Other liver enzymes, including aspartate aminotransferase, alanine phosphatase, and γ-glutamyltransferase (GGT) may be elevated. Elevated GGT is high on the scale but when it was exceedingly high, it was more often an indication of undiagnosed Cushing’s disease. Other liver function tests have been used to support the diagnosis of aflatoxicosis. Serum albumin is often decreased, and prothrombin time is often increased. Serum protein C, antithrombin III, and cholesterol are often decreased in aflatoxicosis.

Postmortem Findings Necropsy is helpful in confirming the diagnosis of aflatoxicosis and ruling out other conditions. Common gross pathology findings include icterus, hepatomegaly that may be mild, ascites, gastrointestinal hemorrhage, and multifocal petechia and ecchymosis. Pigmentary nephrosis has been reported. The primary histologic changes of canine aflatoxicosis are associated with the liver, although necrosis of the proximal convoluted renal tubules has been reported (Hooser and Talcott, 2006). Liver lesions associated with acute aflatoxicosis include fatty degeneration of hepatocytes, which may contain one or many lipid vacuoles. Centrilobular necrosis and canalicular cholestasis are commonly reported. Inflammation is mild. Dogs with subacute toxicosis still have hepatocytic fatty degeneration, canalicular cholestasis, and multifocal-to–locally extensive hepatic necrosis that may be associated with neutrophilic inflammation and hepatocyte regeneration. Fibrosis becomes more prominent, with bridging of portal triads and proliferation of bile ductules. The central vein may become obscured and replaced with dilated sinusoids. Chronic aflatoxicosis is characterized by less fatty degeneration of hepatocytes but marked disruption of the normal hepatic architecture by fibrosis. Regenerative nodules may be evident grossly. Hepatic lesions reported in cats with aflatoxicosis are somewhat different. Experimentally affected cats had

hepatomegaly with petechiation. Hepatocytes contained mostly glycogen with minimal lipid. There was bile duct hyperplasia in cats that had clinical signs for more than 72 hours before death.

Management The prognosis for small animals with clinical signs of aflatoxicosis is guarded. Animals with severe clinical signs often respond poorly to treatment, although early intervention may improve the chances of survival. As with most other conditions, patient assessment and stabilization are the first steps in management of aflatoxicosis. Toxin exposure should be limited. This may mean removing contaminated food after chronic ingestion and replacing it with a diet containing high-quality protein or giving activated charcoal orally for a recent high-dose exposure such as moldy garbage. Supportive care includes correcting hydration and electrolyte imbalances with intravenous fluids. Vitamins B and K1 and dextrose may be added to fluids. Vitamin K1 therapy decreased clinical coagulopathy after 72 hours of therapy in one clinical case (Garland and Reagor, 2007). Parenteral nutrition may be needed in animals with severe gastroenteric signs. Sucralfate and famotidine have been used to treat these animals. Plasma transfusions have been used to improve clotting profiles. Liver protectants such as extracts of milk thistle (Silybum marianum) have been used clinically and experimentally to treat aflatoxicosis. Silymarin is a mix of flavonolignans from milk thistle, including silybin. When given to chickens fed a diet containing aflatoxin B1, changes in liver enzyme profiles and histologic lesions were decreased compared to controls. Various mechanisms of action for silybin have been proposed, such as inhibition of phase I metabolism of aflatoxin B1, thus decreasing epoxide production. Although milk thistle products are believed to be liver supportive, when combined with S-adenosylmethionine (SAM-e) in the face of canine chronic aflatoxicosis presenting acutely, these products may prevent the aflatoxin adducts from forming, thus preventing the aflatoxin from leaving the body. (SAM-e) has also been used clinically as a hepatoprotectant in the treatment of aflatoxicosis (Stenske et al., 2006). Sulfhydryl groups on SAM-e may bind aflatoxin B1 8,9-epoxide. N-acetylcysteine may be given parenterally and has been used in severely intoxicated dogs. N-acetylcysteine is known to increase cytosolic and mitochondrial glutathione and may act directly as a free-radical scavenger. Experimentally N-acetylcysteine has been shown to enhance elimination of aflatoxin B1 and prevent liver damage in poultry. The antischistosomal drug oltripaz has been used to treat aflatoxicosis in humans and experimental animals. Oltipraz inhibits phase I enzymes, CYP1A2 in particular, that metabolize aflatoxin B1 to the epoxide form. It also induces phase II enzymes, including glutathione S-transferase, to facilitate conjugation of aflatoxin B1 8,9epoxide. This drug protects against hepatocarcinogenesis in rats. Oltipraz has not been used in veterinary medicine to our knowledge.

Chapter  36  Nephrotoxicants



References and Suggested Readings Bastianello SS et al: Pathological finding in a natural outbreak of aflatoxicosis in dogs, Onderstepoort J Vet Res 64:635, 1987. Bingham AK et al: Identification and reduction of urinary aflatoxin metabolites in dogs, Food Chem Toxicol 42:1851, 2004. Garland Reagor T: Chronic canine aflatoxin and management of an epidemic. In Panter KE, Wierenga TL, Pfister JA, editors: Poisonous plants: global research and solutions, Wallingford, Oxon, UK, 2007, CABI Publishing. Hooser SB, Talcott PA: Mycotoxins. In Peterson ME, Talcott PA, editors: Small animal toxicology, ed 2, St Louis, 2006, Elsevier Saunders, p 888. Meerdink GL: Mycotoxins. In Plumlee KH, editor: Clinical veterinary toxicology, St Louis, 2004, Mosby, p 231.

CHAPTER 

159

Newbern PM, Butler WH: Acute and chronic effects of aflatoxin on the liver of domestic and laboratory animals: a review, Cancer Res 29:236, 1969. Stenske KA et al: Aflatoxicosis in dogs and dealing with suspected contaminated commercial foods, J Am Vet Med Assoc 228:1686, 2006. Tedesco D et al: Efficacy of silymarin-phospholipid complex in reducing the toxicity of aflatoxin B1 in broiler chickens, Poult Sci 83:1839, 2004. Valdivia AG et al: Efficacy of N-acetylcysteine to reduce the effects of aflatoxin B1 intoxication in broiler chickens, Poult Sci 80:727, 2001. Wang JS et al: Protective alterations in phase 1 and 2 metabolism of aflatoxin B1 by oltipraz in residents of Qidong, People’s Republic of China, J Natl Cancer Inst 91:347, 1999.

36

Nephrotoxicants Wilson K. Rumbeiha, East Lansing, Michigan Michael J. Murphy, St. Paul, Minnesota

T

he kidney is a frequent target for toxic chemicals (Box 36-1). The recent pet food recall associated renal damage has prompted further consideration of nephrotoxicity in dogs and cats. This chapter provides an overview of the more common nephrotoxicants and includes diagnostic considerations for nephrotoxicosis in veterinary patients at the clinic or at the time of postmortem evaluation. Issues related to pet food safety are addressed in Chapter 37.

Pathophysiologic Considerations Renal failure is common, and only a small percent of cases of renal insufficiency are the result of chemical toxins. The kidney constitutes only 1% of body weight in most mammals but receives about 25% of total cardiac output. This high cardiac output exposes the kidney to many substances foreign to the body, including food additives and drugs (i.e., xenobiotics). These chemicals often reach relatively high concentrations in the renal ultrafiltrate. In many instances a high concentration of xenobiotics is associated with nephrotoxicity, but other factors may also play a role.

The kidneys also conduct substantial metabolism of endogenous and exogenous chemicals. Bioactivation of some chemicals can lead to nephrotoxicity, although metabolism of most chemicals leads to detoxification. Animals may be predisposed to nephrotoxicity. Young and geriatric animals generally are believed to be more susceptible to the nephrotoxic effects of xenobiotics. Young animals may not have fully developed detoxifying enzyme systems, and these systems may be diminished in geriatric animals. Malnutrition, dehydration, preexisting renal conditions, and concurrent exposure to multiple nephrotoxins are some of the factors that may influence the potential for nephrotoxicity. Causes of acute renal failure in dogs and cats generally can be classified as hemodynamic-related, infectious, or toxic. Toxin-induced acute renal failure is commonly encountered in small animals. Younger animals are the most frequently involved. In dogs the most common causes of nephrotoxicosis are ethylene glycol (EG), nonsteroidal antiinflammatory drugs, cholecalciferol (CCF), and aminoglycoside antibiotics. In cats the most common causes of nephrotoxicity are EG, CCF, and lilies. An expanded list of known nephrotoxins is

160

Section  II  Toxicologic Diseases

Box  36-1 Known Nephrotoxins and other Causes in the Differential Diagnosis of Acute and Chronic Renal Failure in Dogs and Cats Household Products and Pesticides • Cholecalciferol (see text) • Sodium fluoride, superphosphate fertilizer • Rodenticides (e.g., phosphorus, thallium) • Herbicides (e.g., paraquat) Industrial Compounds • Ethylene glycol (see text) • Chlorinated hydrocarbons (e.g., carbon tetrachloride, chloroform, hexachlorobutadiene) Heavy Metals • Mercury, cadmium, lead, arsenic, chromium Pharmaceuticals, Diagnostic Aids, and Anesthetics • Aminoglycoside antibiotics (see text) • Cephalosporins (e.g., cephaloridine, cefazolin, cephalothin) • Polymyxins • Sulfonamides (e.g., sulfapyridine, sulfathiazole, sulfadiazine) • Amphotericin B • Nonsteroidal antiinflammatory drugs (see text) • Lithium • Phosphorus-containing urinary acidifiers • Cyclosporine • Antineoplastics (e.g., methotrexate, cisplatin) • Methoxyflurane • Chelating agents (e.g., D-penicillamine, ethylenediaminetetraacetic acid [EDTA]) • Radiologic contrast media • Gold salts • Diuretics (e.g., thiazides, furosemide) • Vitamin D3 analog (psoriasis medications) Natural Toxins • Easter lily (Lilium longiflorum; see text) • Mycotoxins (e.g., ochratoxin A, citrinin) • Snake venom • Mushrooms (e.g., amatoxins) Ischemic Renal Injury • Severe volume depletion • Hemolytic compounds (e.g., zinc toxicosis, acetaminophen toxicosis in cats) • Thromboembolism of renal arteries in cats Infectious Conditions • Acute nephritis (e.g., leptospirosis) or pyelonephritis • Chronic tubulointerstitial nephritis Primary Renal Diseases • Chronic renal disease (idiopathic) • Amyloidosis • Familial renal disease Obstructive Uropathy • Melamine cyanurate crystals Ruptured Urinary Conduit

presented in Box 36-1. Only the most common causes of nephrotoxicosis are discussed here, with additional comments directed to the recent pet food–related toxicosis.

Ethylene Glycol And Diethylene Glycol EG is a sweet-tasting liquid that is widely used as a solvent in several commercial products such as antifreeze, paints, and polishes. Antifreeze is the most common source of EG exposure in pets. Commercial antifreeze contains about 50% to 95% EG. EG toxicosis is reported all year round but is more prevalent in late fall and early spring. Toxicosis most commonly occurs within hours of ingestion. EG is rapidly absorbed from the gastrointestinal tract, with peak plasma concentrations occurring about 2 to 3 hours after ingestion. The plasma half-life of EG in small animals is about 3 hours; thus about eight elimination half-lives occur in a day. Diethylene glycol (DEG) is also a widely used organic solvent in commercial products. Antifreeze is the most common source of EG exposure in pets. EG is metabolized predominantly in the liver. It is metabolized from EG to glycoaldehyde by alcohol dehydrogenase. Glycoaldehyde is metabolized to glyoxalate by aldehyde dehydrogenase. Glyoxalate is finally converted to oxalate, glycine, and formate. The conversion of EG to glycoaldehyde and of glycoaldehyde to glycolate requires nicotinamide adenine dinucleotide (NAD) as a cofactor. Lactate dehydrogenase and glycolic acid oxidase catalyze the conversion of glycolate to glyoxylate. The conversion of EG to glycoaldehyde and of glycolate to glyoxalate are the rate-limiting steps in the metabolism of EG. EG itself is mildly toxic, but its metabolite products, especially glycoaldehyde, glyoxalate, and oxalate, are potentially lethal; thus treatment is aimed at preventing this metabolism.

Toxicity and Signs Cats are more sensitive to EG toxicity than dogs. The minimum lethal dose of undiluted EG is 1.4 ml/kg in cats and 4.4 ml/kg in dogs. The clinical presentation of EG toxicosis in dogs and cats is often divided into three phases. The first phase generally is 0.5 to 8 hours after ingestion of a toxic doss. The predominant clinical signs in phase 1 are vomiting, depression, and ataxia (an almost “drunken” appearance). These signs are attributed to EG and glycoaldehyde. The latter reaches a peak plasma concentration 6 to 12 hours after EG ingestion. The second phase is generally 8 to 24 hours after ingestion. The predominant clinical signs in phase 2 are depression, anorexia, tachycardia, and pulmonary congestion. If the animal survives these two phases, the third phase begins about 25 to 72 hours after ingestion. The predominant signs during the third phase include vomiting, anuria or oliguria, and uremia, reflecting acute renal failure. Neurologic signs, including seizures, may be observed in some severe cases of intoxication. Laboratory tests are altered during these phases. An increased anion gap, hyperosmolality, elevated blood urea nitrogen (BUN) and creatinine, hypocalcemia,

Chapter  36  Nephrotoxicants

isosthenuria, and calcium oxalate monohydrate crystals are the biochemical hallmarks of EG toxicosis in small animals. Glycolic and lactic acids are the main causes of acidosis in EG toxicosis. Lactic acid formation is favored by the increase in the ratio of NADH to NAD, which drives the lactate dehydrogenase reaction. Acidosis can be detected as early as 3 to 4 hours after EG ingestion. Acute renal failure is the consequence of the direct toxic effects of EG metabolism on renal epithelial cells and on the tubular obstructive effects of calcium oxalate crystals. Hyperechoic renal cortices may be evident on ultrasound examination of the kidneys. Bladder size may be small, indicating reduced urine formation.

Treatment of Ethylene Glycol Toxicosis Treatment of EG toxicosis is most successful if initiated within 12 hours of ingestion (also see Chapters 24 and 29). Gastric decontamination should be initiated by inducing emesis, followed by administration of activated charcoal, provided the patient is presented within 4 to 6 hours of ingestion. Previously intravenous ethanol was the treatment of choice for EG toxicosis, but with approval of 4-methylpyrazole (4-MP) for EG toxicosis in dogs the situation has changed. However, ethanol is still the drug of choice for cats. Ethanol is a preferred substrate of alcohol dehydrogenase; thus it is used to inhibit EG metabolism. However, ethanol is normally of little use if the patient is presented more than 12 hours after ingestion. A 20% ethanol solution is given at 5.5  ml/kg intravenously every 4 hours for 24 hours or in a constant-rate infusion of 1.4  ml/kg/hour for dogs or 1.25  ml/kg/hour for cats. Maintaining ethanol therapy for up to 72 hours normally ensures complete EG elimination. The benefit of ethanol treatment has been questioned, especially in high-exposure situations and comatose animals. Currently other alcohol dehydrogenase inhibitors may be used to inhibit conversion of EG. The drug 4-MP or Fomepizole (Orphan Medical) is approved for use in dogs (Kirk and Bonagura, 1995). The first dose is given as a 5% solution at 20  ml/kg intravenously. The second dose is given at 15  mg/kg 12 to 24 hours after the first dose. The third dose, if necessary, is given at 5  mg/kg 36 hours after the first one. Unfortunately 4-MP is not recommended in cats, partly because of poor efficacy in this species when using canine doses and the need to administer the drug almost concurrently with ingestion of EG. Hemodialysis is a referral option in some areas and may be beneficial if started up to 24 hours after EG ingestion. However, dialysis is most effective when initiated within 3 to 4 hours of exposure. Further studies are needed to determine if hemodialysis removes the more toxic metabolites of EG, the time frame over which this therapy is beneficial, and whether or not 4-MP can be used in conjunction with hemodialysis. Because most patients are presented for treatment late in the course of the disease, the mortality rate of EG toxicosis is higher than 70%. Treatment procedures for EGinduced nephrotoxicosis are summarized in Box 36-2 and Chapter 191. DEG is also rapidly absorbed from the gut, with peak plasma concentrations reached in 1 to 2 hours.

161

Box  36-2 Summary of General and Supportive Treatment of Toxic-Induced Acute Renal Failure Keep the Patient Alive If Presented Less than 6 hours After Ingestion • Emesis Apomorphine hydrochloride, 0.02-0.04 mg/kg IV or IM (if available) Syrup of ipecac, 2-6 ml PO or 3% hydrogen peroxide, 5 ml/dog or cat • Activated charcoal Acta-Char, 1-4 g/kg or Charcodote, 6-12 ml/kg • Cathartics Mineral oil, 10-50 ml/dog, 10-25 ml/cat q12h PO or Sodium sulfate, 1 g/kg Supportive Treatment • Hyperkalemia and acidosis Sodium bicarbonate, 10 mg/kg q8-12h PO or BW (kg) × 0.3 × base deficit or (20 − TCO2) in mEq; half of this dose is given slowly IV in 15-30 min • Fluid therapy Ideal fluid is 0.9% normal saline, or 2.5% dextrose in 0.45% saline; to enhance urinary excretion of toxin, correct electrolyte imbalances, manage moderate acidosis, dilute waste products normally excreted by the kidneys • Diuretics to enhance toxin and metabolic waste products excretion Furosemide (avoid in gentamicin nephrotoxicity), 2-4 mg/kg as needed IV, IM, SC Mannitol, 1 g/kg of 5%-25% solution IV (avoid in pulmonary edema) • Antiemetics or H2 blockers to correct uremia-induced vomiting Metoclopramide, 0.2-0.5 mg/kg IV, IM, q6-8h or Cimetidine, 2.5-5 mg/kg IV q8-12h • Give proper nutrition: glucose supplementation, low­quantity but high-quality protein • Peritoneal dialysis or hemodialysis if azotemia is progressive despite fluid therapy Run Toxicology Tests to Identify and Remove Specific Underlying Causes • Withdraw offending drug; eliminate sources (e.g., feed); give chelation therapy in cases such as exposure to heavy metals BW, Body weight; IM, intramuscularly; IV, intravenously; PO, orally; SC, subcutaneously.

It is metabolized in the liver to its sole metabolite, 2-hydroxyethoxyacetic acid. Oxalate is not a metabolite of pure DEG. DEG is excreted in urine as both parent compound and metabolite. Toxicosis of DEG is characterized by renal failure, acidosis, and cardiac irregularities. The diagnosis of DEG nephrotoxicosis is difficult and

162

Section  II  Toxicologic Diseases

can be supported by its presence or that of its metabolite in blood or urine. Ethers of EG such as EG butyl ether, a component of glass cleaners, may also cause oxalateinduced renal failure.

Aminoglycoside Antibiotics Aminoglycoside antibiotics are the most frequent class of drugs associated with nephrotoxicosis in dogs and cats. Gentamicin, tobramycin, amikacin, kanamycin, and netilmicin are used for the treatment of gram-­negative infections but have a narrow therapeutic index and should be used with caution in animals at high risk for nephrotoxicity, especially those suffering from dehydration or receiving diuretic (furosemide) therapy. Aminoglycosides are not metabolized in vivo and, because of their low molecular weights and high water solubility, are excreted almost exclusively through the urine. In vivo these antibiotics easily ionize to cationic complexes that bind to anionic sites on the epithelial cells of the proximal tubules. Following binding, the drugs are internalized by pinocytosis. Renal cortical concentrations of aminoglycoside antibiotics may exceed plasma concentration by tenfold. In general, the toxicity of aminoglycoside antibiotics correlates positively with the number of ionizable groups on the drug. For example, neomycin with six ionizable groups is extremely nephrotoxic and is not used systemically. Gentamicin, tobramycin, amikacin, kanamycin, and netilmicin all have five ionizable groups and a high potential for renal toxicity when used systemically. Aminoglycoside antibiotics can cause acute tubular necrosis through a variety of mechanisms. Aminoglycoside-induced renal failure is most commonly iatrogenic in origin. Animals receiving aminoglycoside therapy should be monitored for renal injury with periodic urinalyses (specifically evaluation for protein and casts) and with serial determinations of serum urea nitrogen and creatinine. The mortality rate in monitored animals is low. Clinically affected animals may have polyuria, proteinuria, azotemia, and high urinary N-acetyl-B-D-glucosaminidase activity. Nephrotoxicity often can be prevented by increasing the dosage interval by a factor related to the serum creatinine concentration. For example, if the recommended dosing interval is 8 hours and the serum creatinine concentration is 3 mg/dl, the dosing interval should be extended by 3 × 8 hours = 24 hours. The treatment of aminoglycoside-induced nephrotoxicosis consists of withdrawing aminoglycoside therapy and then initiating other nonspecific measures, as summarized in Box 36-2 and Chapter 191.

Nonsteroidal Antiinflammatory Drugs Nonsteroidal antiinflammatory drugs (NSAIDs) have diverse chemical structures but similar pharmacologic effects. These drugs are broadly classified into two groups: the carboxylic acids and the enolic acids. Aspirin, indomethacin, tolmetin, sulindac, naproxen, ibuprofen, and flunixin meglumine belong to the ­ carboxylic

acid group. Phenylbutazone and piroxicam belong to the enolic acid group. Additional classification is based on inhibition of specific enzymes (e.g., COX-1 or COX-2 inhibition). Many NSAIDs are sold over the counter and are widely available in homes. Because of their wide availability, the accidental ingestion of these medications is encountered commonly in small animal practice. Dogs are more involved frequently than cats with acute toxicosis. Iatrogenic NSAID toxicosis is encountered occasionally, is often chronic, and may be to the result of the higher sensitivity of some animals than others to these drugs. Dehydration, poor renal perfusion (as in heart failure), and concurrent treatment with corticosteroids may increase the likelihood of toxicosis. The NSAIDs are a diverse group of compounds. In general, NSAIDs are well absorbed orally and predominantly metabolized in the liver. Some NSAIDs such as aspirin require glucuronidation. Cats are especially sensitive to the toxicosis of NSAIDs because they have a reduced glucuronic acid conjugating capacity. Nephrotoxicity is certainly not the only adverse effect of NSAIDs. In particular, hepatopathy and gastrointestinal erosions and ulceration pose serious risks to veterinary patients. Gastric and intestinal toxicity often creates signs of anorexia, vomiting, diarrhea, and anemia. Furthermore, these drugs can enhance bleeding tendencies and, especially in cats, predispose to methemoglobinemia. The nephrotoxic effects of these compounds are discussed in the following paragraphs. The nephrotoxic and antiinflammatory effects of NSAIDs pertain to the ability of these drugs to inhibit prostaglandin production. Most NSAIDs inhibit cyclooxygenase, the enzyme responsible for conversion of arachidonic acid to endoperoxides. Endoperoxides are intermediates in prostaglandin synthesis. Ibuprofen, mefenamic acid, and indomethacin reversibly inhibit cyclooxygenase, whereas aspirin and phenylbutazone inhibit it irreversibly. Some NSAIDs may block prostaglandin receptors. Ingestion of large doses of NSAIDs may induce acute renal failure. Chronic exposure to toxic doses of NSAIDs may cause renal papillary necrosis. Dehydrated animals, animals in shock, and those with preexisting renal disease are most vulnerable to NSAID-induced nephrotoxicity. Diagnostic tests of value include a careful history, examination of the stool for melena, urinalysis, tests of renal function, serum biochemistries reflecting liver injury, and a complete blood count. The treatment of acute NSAID toxicosis should involve gastrointestinal decontamination with emetics and activated charcoal (see Chapter 24), intravenous fluid therapy to correct acidosis and maintain urine output, and other life-support measures as needed (see Box 36-2.) The gastrointestinal tract should be treated for potential ulceration and protected from further injury with drugs such as famotidine, omeprazole, sucralfate, or misoprostol (see Chapter 114). In chronic toxicosis the offending drug should be withdrawn. The prognosis is generally good in acute renal injury but is guarded to poor in chronic exposure situations when renal papillary necrosis has occurred.



Cholecalciferol CCF (vitamin D3) is marketed as a rodenticide as well as a nutritional supplement and a treatment for psoriasis. Toxicosis from this compound is related to disruption of calcium homeostasis. CCF toxicosis should always be considered whenever acute renal failure is observed in pets. Rat baits containing CCF are sold over the counter as Quintox (Bell Laboratories), Rampage (Motomco Ltd.), Rat-B-Gon (The Ortho Group), and other trade names. Poisoning in pets occurs after accidental or intentional bait ingestion. Ingestion (including licking) of human psoriasis medications that contain synthetic vitamin D, analogs such as calcipotriol and calcipotriene, can lead to vitamin D toxicosis. These creams are dispensed under trade names that include Dovonex (Westwood Squibb Pharmaceutical Corp), Taclonex (Warner-Chilcott Company Inc.), or Psorcutan (Intendis). Although the median lethal dose (LD50) of CCF in dogs is widely reported to be 43 to 88 mg/kg, the experience in my laboratory is that as little as 10 mg/kg given once orally can be lethal. Normal dogs that ingest as little as 4 to 6 mg/ kg of CCF once may become sick. Clinically normal dogs that ingest single doses of 2 mg/kg of CCF may develop serum calcium concentrations greater than 12.5 mg/dl. CCF is rapidly absorbed after ingestion and then transported to the liver. CCF is stored and then slowly metabolized to 25-hydroxy-vitamin D3 (25-OH-D3). Then 25-OH-D3 is metabolized to calcitriol (1,25-dihydroxyvitamin D3), the active metabolite of CCF in the kidney. Calcitriol stimulates calcium uptake from the gut. In conjunction with parathyroid hormone, calcitriol mobilizes calcium from bone tissue and conserves calcium by enhancing calcium resorption from distal tubules. It is known that high serum concentrations of 25-OH-D3 stimulate the 1,25OH-D3 receptors and trigger similar events. The combined result of these effects is hypercalcemia and hyperphosphatemia, an important point in the differential diagnosis of hypercalcemia or recent onset. Calcification of soft tissues, especially the kidneys, occurs when the calcium and phosphorous product (in milligrams per deciliter) exceeds 60. Renal calcification starts 12 to 18 hours after ingestion, but peak elevation may not be observed until 48 to 72 hours after CCF exposure, coinciding with elevations in serum BUN and creatinine. Early signs of CCF toxicosis include anorexia, vomiting, melena, and depression. If there is no known history of ingesting bait or psoriasis cream, the clinical signs of toxicosis may be relatively nonspecific. Signs of hypercalcemia, including polydipsia, polyuria, vomiting, and constitutional illness, may be evident. Isosthenuria is typical. Hypercalcemia and hyperphosphatemia should prompt consideration of vitamin D toxicosis, especially if renal function is still normal. However, other causes of hypercalcemia must be considered, including malignancies (lymphoma, perianal adenocarcinoma, parathyroid tumors), renal failure, and hypoadrenocorticism.

Treatment of CCF Toxicosis Treatment of hypercalcemia related to CCF toxicosis can be challenging (see also Chapter 54). Mortality rate is high

Chapter  36  Nephrotoxicants

163

because animals are often presented late in the course of disease after substantial renal injury has already occurred. Nonspecific gastrointestinal tract decontamination procedures should be attempted if the animal is presented within 6 to 8 hours of known ingestion (see Chapter 24). Specific therapy is aimed at lowering blood calcium to 8 to 11 mg/dl with the use of salmon calcitonin or another drug. The recommended dosage of calcitonin is 4 to 6 units subcutaneously every 4 to 6 hours until the calcium stabilizes (at least 3 weeks). Pamidronate disodium given at 1.2 mg/kg by a slow saline infusion over 2 hours has been shown to be an effective alternative therapy to calcitonin. Two intravenous infusions of pamidronate given 8 days apart have been shown to reverse hypercalcemia of 16 mg/dl to normal for 28 days. Other biphosphonate drugs have been used successfully for treatment of vitamin D–related toxicosis and hypercalcemias of different etiologies but should only be used after consulting an internal medicine specialist or toxicologist. Nonspecific treatment (see Box 36-2) is frequently used in conjunction with specific calcium-lowering therapies, including furosemide at 2.5 to 4.5 mg/kg every 8 to 16 hours, prednisone at 2 to 6 mg/kg intravenously, intramuscularly, or orally every 24 hours or until blood calcium concentrations return to normal. Fluid therapy with normal saline (0.9% NaCl) is recommended to enhance urine flow and calcium excretion and to correct dehydration.

Toxic Ornamental Plants Ingestion of leaves, flowers, or both of the Easter lily (Lilium longiflorum) may cause nephrotoxicity in cats. Lily toxicosis in cats was first reported in 1992 and has subsequently been reproduced experimentally. Shortly after eating leaves or flowers, cats develop signs of gastrointestinal upset and become depressed. Acute renal failure characterized by polyuria, dehydration, proteinuria, and glucosuria may be observed 48 to 96 hours after exposure. The toxic agent and mechanism of toxicity have not been established. The recommended nonspecific therapy includes gastrointestinal decontamination with the use of emetics, activated charcoal, sodium sulfate, and fluid therapy to correct dehydration (also see Chapter 191). This treatment approach is most likely to be beneficial when performed within 6 hours of plant exposure.

Diagnostic Approach to Suspected Nephrotoxicity Nephrotoxicosis associated with consumption of pet food is quite rare. Yet several million pouches, cans, and bags of pet food were recalled during the spring of 2007 following calls into Regional Offices of the Food and Drug Administration after reports of possible pet food–related nephrotoxicity. Distal renal tubular degeneration and necrosis with crystals deposition were reported in most dogs and cats ingesting pet foods associated with this recall. At the conclusion of the episode, about 300 cats and dogs died and about an equal number were clinically affected but recovered with treatment. This extensive recall included the United States and Canada.

164

Section  II  Toxicologic Diseases

Diagnostic laboratories and the Food and Drug Administration (FDA) have identified the presence of melamine, ­ ammelide, ammeline, and cyanuric acid in some recalled products. The presence of melamine and its analogs is unprecedented in the feed industry. Experimental studies in cats and pigs have revealed that crystal formation was a result of melamine cyanurate crystals. These crystals caused tubular blockage and distal tubular epithelial necrosis. Aspects of pet food safety are discussed in more detail in Chapter 37. The following discussion considers general concepts of diagnosis in terms of nephrotoxicity.

Critical Issues in Establishing Diagnosis of Food-Related Nephrotoxicity A fundamental part of medicine is consideration of the differential diagnosis. As can be seen from Box 36-1, the causes of acute renal failure in dogs and cats are extensive. Refinement of a diagnosis usually relies on the history, clinical signs, physical examination, and results of laboratory testing. The goal in toxicology cases is establishing an etiology. Often the facts necessary for such a conclusion are not evident; and morphologic, presumptive, or clinical diagnoses are made. The nephrotoxins EG, CCF, NSAIDs, aminoglycoside antibiotics, and Lilium spp. are further examined here to illustrate the point. Two tenants of toxicology are exposure and dose response. Pets must be exposed to a toxin for it to cause a toxicosis. Further, they must be exposed to a potentially toxic dose and have the adverse effect previously demonstrated for that toxin before a clinician can reach a conclusion of a toxicosis. In veterinary patients the history and specific laboratory tests are normally used to determine whether an animal has been exposed to a nephrotoxin. The history is often the less reliable of the two methods. For example, does the owner know if his or her pet was exposed to a potentially toxic dose of a drug (NSAIDs, aminoglycosides) with demonstrated nephrotoxicity? Specifically one might inquire if EG, CCF, NSAIDs, aminoglycosides, or Lilium spp. plants are present in or around the home. If so, the next step is to confirm or rule out exposure by specific laboratory testing when available. Tests should identify the parent compound or its metabolites. Quick screening tests are often used to make treatment decisions, but analytic laboratory tests may be required to confirm an etiologic diagnosis. The availability of such confirmatory tests may be investigated by contacting a veterinary diagnostic laboratory (see www.aavld.org or www.abvt.org). Serum or urine is usually the specimen of choice in live animals. For example, although calcium

oxalate crystals in urine might be present in toxicosis in a dog or cat with renal failure, this finding is nonspecific; so serum, urine glycolic acid, or EG concentrations would better support a diagnosis of EG exposure. Similarly serum concentrations of 25-hydroxycholecalciferol are used to indicate exposure to CCF; serum or urine concentrations of NSAIDs and aminoglycosides may be used for the same purpose. The clinical signs, physical examination findings, and routine laboratory tests may be instructive. Clinical signs of renal toxicosis often include gastrointestinal upset, central nervous system depression, cardiopulmonary invol­ vement, and acute renal failure, as observed with EG toxicosis. Ultrasound may show renal cortical damage. Involvement of other organ systems may provide diagnostic leads. For example, NSAID toxicosis causes often may include gastrointestinal bleeding and ulceration, acidosis, and mild elevations of hepatic enzymes. Clinical signs of CCF toxicosis include dark bloody feces, oliguria, or polyuria. Laboratory testing often is required to establish the adverse effects of toxicity. Obviously serum urea nitrogen and creatinine along with urinalysis are used clinically to indicate renal injury. Calcium abnormalities are common with EG and with CCF toxicosis. Values within the normal range for all of these tests would be interpreted as arguing against a diagnosis of nephrotoxicity. Such findings may not exclude exposure to a subtoxic dose of a nephrotoxic chemical. When a patient dies or is euthanatized, necropsy and histopathology findings can in some instances support an argument of exposure to a toxin. For example, the finding of antifreeze solution, CCF rodenticide bait, drug products, or lily plant parts supports exposure to the respective compounds. The observation of birefringent crystals histologically is very suggestive of EG exposure, but even in this case the findings are not specific. For example, such crystals can occur following exposure to soluble oxalates (Oxalis spp. plants). Similarly renal mineralization is compatible with, but not specific for, CCF exposure. In conclusion, the diagnosis of nephrotoxicity must rely on evidence of exposure to a sufficient quantity of a toxic chemical, clinical or analytic laboratory findings that confirm or strongly suggest toxicosis, and clinical or necropsy findings of compatible illness. These same principles should be applied to the diagnosis of new toxicities, including those implied by the recent pet food recall.

Reference and Suggested Reading Kirk RW, Bonagura JD, editors: Kirk’s current veterinary therapy XII (small animal practice), Philadelphia, 1995, Saunders, p 232.

CHAPTER 

37

Food Toxicoses in Small Animals Michael J. Murphy, St. Paul, Minnesota Julie Churchill, St. Paul, Minnesota

“On March 15, FDA learned that certain pet foods were sickening and killing cats and dogs. FDA found contaminants in vegetable proteins imported into the United States from China and used as ingredients in pet food.”  (http://www.fda.gov/oc/opacom/hottopics/ petfood.html)

T

his announcement marked the beginning of one of the most significant recalls of pet food in the United States and Canada. The chemicals melamine, ammiline, ammilide, and cyanuric acid were identified in pet food within weeks of the initial Food and Drug Administration (FDA) announcement. The presence of these chemicals in pet food was unprecedented and judged to be adulteration. A number of dogs and cats known to have eaten these foods were also treated for clinical signs associated with a laboratory finding of acute renal failure. Questions related to the disease associated with foods subjected to this recall remain. Certainly the demonstration of nephrotoxicity from any chemical requires consideration of both diagnostic and toxicologic principles. Since this recall many pet owners have become wary of commercial pet foods. Some are seeking nutritional advice and considering alternative diets such as raw meat diets or home-prepared diets. This chapter is designed to complement the general chapter on “Pet Food Safety” by the late Dr. Phillip Miller (see Section II on Evolve). Herein we consider the pet food recall, commercial pet food regulation, and some issues related to homemade pet food diets. The diagnosis and management of chemical nephrotoxicity is detailed in Chapter 36, and the treatment of acute renal failure outlined in Chapter 191.

Pet Food Recall Many United States pet food companies voluntarily recalled some of their product after the FDA’s March 15, 2007 announcement. Investigations by the FDA, veterinary diagnostic laboratories, and the pet food industry led to the identification of melamine and its analogs in some lots of pet food. The presence of melamine in some pet food led the FDA and pet food companies to consider the melamine-containing pet food as adulterated. Consequently several pet food companies voluntarily recalled millions of pounds of potentially adulterated product. The recalls proceeded under established FDA regulations. The unprecedented adulteration of some pet food with melamine led to the widespread pet food recall.

Since widespread product recalls are not common, a brief summary of the regulatory basis for recalls is presented. “Food,” “adulterated,” and “recall” all have FDA definitions. “The term “food” means (1) articles used for food or drink for man or other animals, … and (3) articles used for components of any such article.” 21 United States Code, Section. 321 (f)

Pet food is an article used for food for animals; thus it fits the FDA legal definition of “food.” Pet food is comprised of many components. Some of these components may also meet the FDA’s legal definition of “food.” Wheat gluten is an example of such a component. Some of the recalled pet food was judged to be adulterated. “A food shall be deemed to be adulterated– … (4) if any substance has been added thereto or mixed or packed therewith so as to … make it appear better or of greater value than it is.” 21 United States Code, Section. 342 (b)(4).

Adding a substance to a food component to “make it appear better or of greater value than it is” is commonly referred to as “economic adulteration.” One theory proposed is that melamine was added to wheat flour as an economic adulterant. The economic adulterant theory proposes that mela­ mine was added to wheat flour to increase the measured concentration of protein in the wheat flour to that of wheat gluten. Wheat flour is generally lower in protein than wheat gluten. Generally the protein concentration is calculated by testing the product for its total nitrogen con­centration and then multiplying the total nit­rogen conce­ntration by 6.25 to determine the total protein concentration. Melamine contains six nitrogen molecules per molecule. Addition of melamine to wheat flour apparently increased the calculated protein concentration from that of flour to that of wheat gluten. Because wheat gluten is purchased in large part based on its protein concentration, the price for wheat gluten is higher than the price for wheat flour. Consequently the addition of melamine to wheat flour made the flour “appear better or of greater value” than the flour would have been without the addition of the melamine, thereby satisfying the definition of adulteration. The melamine-adulterated wheat flour was used as a component in the manufacture of a number of pet food products. One means of removing an adulterated product from the marketplace is a product recall. 165

166

Section  II  Toxicologic Diseases

“Recall means a firm’s removal or correction of a marketed product that the Food and Drug Administration considers to be in violation of the laws it administers and against which the agency would initiate legal action, e.g., seizure. …” 21 CFR 7.3 (g)

The company frequently initiates the recall of a marketed product. “A firm may decide of its own volition and under any circumstances to remove or correct a distributed product. A firm that does so because it believes the product to be violative is requested to notify immediately the appropriate Food and Drug Administration district office listed in § 5.115 of this chapter. …” 21 CFR 7.46(a)

Many pet food companies chose to recall pet food products that had been distributed and to notify the FDA of their recall. A list of these recalled products was posted on the FDA website at http://www.accessdata.fda. gov/scripts/petfoodrecall/. It should be emphasized that not all adulterated products are poisonous. Adulteration is not equivalent to intoxication. Apparently melamine was an economic adulterant in some finished pet food, and this chemical also was detected in the kidneys and urine of some cats that died of renal failure. However, at the time of this writing, the FDA was not “fully certain that melamine is the causative agent” of the cats’ death (FAQ, 2007). Investigations are ongoing regarding links between adulteration, specific toxins, and the clinical consequences of toxicosis.

Pet Food Regulation The pet food recall has given rise to questions of regulation of the pet food industry. The widespread pet food recall demonstrates that considerable regulatory authority over the pet food industry exists. The FDA and American Association of Feed Control Officials (AAFCO) are the two major sources of pet food regulation in the United States. The FDA administers the Federal Food, Drug, and Cosmetic Act (FFDCA). The FFDCA requires that “pet foods, like human foods, be pure and wholesome, safe to eat, produced under sanitary conditions, contain no harmful substances, and be truthfully labeled.” (FAQ, 2007). The FDA also “ensures that the ingredients used in pet food are safe and have an appropriate function in the pet food.” The “mineral and vitamin sources, colorings, flavorings, and preservatives may be generally recognized as safe or must have approval as food additives” (FAQ, 2007). For example, the FDA monitors bacteria, mycotoxins, pesticides, and metals in commercial pet food products. The FDA and many states require the listing of food ingredients on the label. Specifically the FDA requires “proper identification of the product, net quantity statement, name and place of business of the manufacturer or distributor, and a proper listing of all the ingredients in order from most to least, based on weight” (FAQ, 2007). Most states also have pet food labeling requirements. These state requirements generally are based on AAFCO standards. AAFCO is an association of state and federal officials with the basic goal of providing “a mechanism

for developing and implementing uniform and equitable laws, regulations, standards and enforcement policies for regulating the manufacture, distribution and sale of animal feeds; resulting in safe, effective, and useful feeds” (AAFCO website). Although AAFCO provides nutritional guidelines related to feeds, complaints about a pet food product are generally directed to the state Department of Agriculture or to the FDA. Complaints to the FDA are normally made to the district office consumer compl­ aint coordinator. The contact information for the district offices can be found at: http://www.fda.gov/opacom/ backgrounders/complain.html (also see Chapter 20).

Some Issues Relevant to Homemade Pet Foods As with any feed, home-prepared pet diets are also subject to consideration for a number of health and stability factors. Among these are microbial content, aerobic stability, unsafe ingredients, and nutritional imbalances.

Microbial Content A great many recipes for homemade pet food have been posted on the Internet since the pet food recall. Bacterial contamination is a critically important issue in the preparation of homemade pet foods. Generally speaking, microorganisms may grow in an environment in which the pH is greater than 4.6 and the water activity is greater than 0.85(21 CFR 113.3[n]). The FDA requires that canned pet foods be processed under regulations to ensure the contents are free of viable microorganisms. Many microorganisms of concern are found in human foods. These organisms include Clostridium perfringens, Clostridium botulinum, Staphylococcus aureus, Bacillus cereus, Salmonella spp., Listeria spp., Yersinia spp., Aeromonas spp., Campylobacter spp., Escherichia coli, Vibrio spp., Enter­ococcus faecalis, Enterobacter cloacae, and Klebsiella ozaenae. Other microorganisms to consider in raw meat include Neorickettsia spp., Toxoplasma gondii, Neospora canis, Echinococcus spp., and Trichinella spiralis. The presence of microorganisms in uncooked meat may serve as a primary source of disease in pets. Similarly the growth of microorganisms on food during or after preparation should be considered, particularly if the food is not prepared daily. Disease in dogs from Clostridium botulinum, Escherichia coli 0157:H7, and Salmonella spp. in both dogs and cats has been reported (Barsanti, Walser, and Hatheway, 1978; Fenwick, Hertzke, and Cowan, 1995; Chengappa et al., 1993; Stiver et al., 2003). Feeding raw meat can be dangerous not only to pets but also the people who care for them. Pathogenic bacteria from raw meat can contaminate work surfaces in the kitchen, utensils, dishes, the floor where the dog eats, and food and water bowls. This exposure poses an even greater risk in households with children, the elderly, or immunocompromised individuals.

Aerobic Stability The aerobic stability of home-prepared food may also be an issue. Antioxidants are added to many prepared

human food and commercial pet food products to reduce oxidative decomposition. Foods demonstrating oxidative decomposition are commonly referred to as rancid. Diets high in fat are particularly prone to rancidity, which can include destruction of fat-soluble vitamins. Rancidity and microbial growth are two causes of the “garbage gut” syndrome so often seen by practitioners in dogs and cats that have eaten improperly stored food. A similar situation may occur if home-prepared pet foods are not safely constituted or stored before feeding.

Toxic Human Foods Many animal owners are unaware of the potential adverse effects of “human foods” on their pets. Although not specifically contaminated or rancid, these foods may contain chemicals or natural substances that are toxic to dogs and cats. For example, some human foods worth avoiding in homemade pet food recipes are Alliuim species (chives, onions, garlic), Brassica species (kale, Brussels sprouts), kelp, avocado, ­methylxanthine­containing products (chocolate), rhubarb, grapes, raisins, macadamia nuts, green potatoes, or tomatoes. A number of herbal products should also be avoided (see Chapters 23 and Chapter 34).

Nutritional Imbalances Nutritional balance is a pivotal aspect of commercially prepared pet foods. A commercial product labeled as dog or cat “food” is by definition a complete and balanced product for that species and requires a nutritional adequacy statement on the product label. Of course there is no requirement or assurance of nutritional adequacy or nutritional balance in recipes published in books or downloaded from the Internet. The nutrient requirements of dogs and cats have recently been reviewed (NRC, 2006). Energy, carbohydrate and fiber, fat and fatty acid, protein and amino acid, mineral, vitamin, and water requirements of dogs and cats are known (NRC, 2006). Although energy, carbohydrate, fat, and protein may be considered by individuals making pet foods, over time vitamin or mineral imbalances may be difficult to avoid. Nutritional imbalance is more likely to occur with high-protein diets based on meat or raw meaty bones. For example, calcium deficiencies have been documented to occur in meat diets. Diets with high meat content have very high concentrations of dietary phosphorus and low concentrations of calcium. Although it seems that the bones should offer a rich supply of calcium, larger pieces of bones do not appear to be digested and absorbed efficiently. This may result in nutritional deficiency even though bone is intended to serve as the calcium source. The availability of calcium to the dog is highly variable, depending on the size and amount of bones and the age and health of the animal. For example, if the diet contains a very high amount of ground bone, it could be potentially high in calcium, which can be especially harmful to large-breed puppies. High dietary calcium is also believed to contribute to a number of developmental bone diseases such as hip dysplasia, angular limb deformities, and cartilage abnormalities, including osteochondritis desiccans.

Chapter  37  Food Toxicoses in Small Animals

167

Mineral imbalances have also been associated with ­anemia, goiter, rickets, and secondary hyperparathyroidism. Vitamin imbalances may also occur in homemade diets. Homemade diets based on meats using offal or high amounts of liver can result in vitamin A excesses and potential toxicity. Raw-meat diets tend to be high in fat, which can lead to either excessive or deficient absorption of the other fat-soluble vitamins. Vitamin imbalances have been associated with anemia, anorexia, dystrophic mineralization, hyperesthesia, myelin degeneration, osteo­ porosis, reduced growth, and a number of other diseases. Amino acid deficiencies may also occur in homemade diets. A number of amino acids are classified as being indispensable or essential: 11 for cats and 10 for dogs. These essential amino acids must be supplied in the diet because they cannot be synthesized in the body. Most meat-based diets provide adequate amounts of essential amino acids. However, with the new trend toward vegetarian pet diets and with homemade feline diets, careful attention to the amino acid composition is needed to ensure nutritional adequacy. Because most nutritional problems do not cause noticeable abnormalities until the nutritional imbalance has been present for many months, the link to diet may be hard to identify. Perhaps the best advice for the client insisting on home-prepared pet diets is the following: Question the credentials and training of those advocating the diets and select a recipe that has been formulated by a board-certified veterinary nutritionist. These issues associated with pet food safety should encourage veterinarians to record a detailed and accurate diet history in the medical record. It is uncertain if pet food changes made by clients in response to the recall in 2007 will result in an increased prevalence of nutrition-based diseases, but veterinarians should be on the lookout for problems related to bacterial contamination, spoiled or rancid food, human food toxicity, or nutritional imbalances.

References and Suggested Reading American Association of Feed Control Officials: http://www. aafco.org/ Barsanti JA, Walser M, Hatheway CL: Type C botulism in American foxhounds, J Am Vet Med Assoc 172: 809, 1978. Chengappa MM et al: Prevalence of Salmonella in raw meat used in diets of racing greyhounds, J Vet Diagn Invest 5:372, 1993. Delay J, Laing J: Nutritional osteodystrophy in puppies fed BARF diet, Animal Health Laboratory Newsletter, vol 6, no 2, 2002, Ontario, University of Guelph. FAQ: accessed 10 July 2007 from http://www.fda.gov/cvm/ MenuFoodRecallFAQ.htm. See also 21 CFR, Parts 73, 74, 81, 573 and 582; FDA Regulation of Pet Food and Information on Marketing a Pet Food Product; and Interpreting Pet Food Labels and Interpreting Pet Food Labels—Special Use Foods. Fenwick B, Hertzke DM, Cowan LA: Alabama rot: almost the complete story, Proceedings of the Eleventh Annual International Convention Canine Sports Medicine Symposium, Gainsville, Fla, 1995, p 15. Freeman LM, Michel KE: Evaluation of raw food diets for dogs, J Am Vet Med Assoc 218:705, 2001.

168

Section  II  Toxicologic Diseases

Joffe DJ, Schlesinger DP: Preliminary assessment of the risk of Salmonella infection in dogs fed raw chicken diets, Can Vet J 43:441, 2002. LeJeune JT, Hancock DD: Public health concerns associated with feeding raw meat diets to dogs, J Am Vet Med Assoc 219:1222, 2001. Miller EP: Pet food safety. In Bonagura JD, editor: Kirk’s current veterinary therapy XIII (small animal practice), Philadelphia, 2000, Saunders, p 236. National Research Council: Nutrient requirements of dogs and cats. National Academy of Science, Government Printing Office, 2006.

Stiver SL et al: Septicemic salmonellosis in two cats fed a rawmeat diet, J Am Anim Hosp Assoc 39:538, 2003. Stogdale L, Diehl G: In support of bones and raw food diets, Can Vet J 44(10):783, 2003. Stone GG et al. Application of polymerase chain reaction for the correlation of Salmonella serovars recovered from Greyhound feces with their diet, J Vet Diagn Invest 5:378, 1993.

s e c t i o n III Endocrine and Metabolic Diseases Mark E. Peterson

Chapter 38: Interpretation of Endocrine Diagnostic Test Results for Adrenal and Thyroid Disease................................................................... 170 Chapter 39: Medical Treatment of Feline Hyperthyroidism............................. 175 Chapter 40: Radioiodine for Feline Hyperthyroidism...................................... 180 Chapter 41: Hypothyroidism............................................................................ 185 Chapter 42: Obesity........................................................................................... 191 Chapter 43: Canine Diabetes Mellitus.............................................................. 196 Chapter 44: Feline Diabetes Mellitus................................................................ 199 Chapter 45: Diet and Diabetes.......................................................................... 204 Chapter 46: Diabetic Monitoring...................................................................... 209 Chapter 47: Complicated Diabetes Mellitus..................................................... 214 Chapter 48: Atypical and Subclinical Hyperadrenocorticism........................... 219 Chapter 49: Canine Hyperadrenocorticism...................................................... 224 Chapter 50: Adrenal Insufficiency in Critical Illness........................................ 228 Chapter 51: Hypoadrenocorticism.................................................................... 231 Chapter 52: Idiopathic Feline Hypercalcemia . ................................................ 236 Chapter 53: Treatment of Hypoparathyroidism............................................... 241 Chapter 54: Canine Hypercalcemia and Primary Hyperparathyroidism . ....... 247 VOLUME XIII CONTENT ON EVOLVE: http://evolve.elsevier.com/Bonagura/Kirks/ Clinical Use of the Vasopressin Analogue DDAVP for the Diagnosis and Treatment of Diabetes Insipidus Complications and Concurrent Conditions Associated With Hypothyroidism in Dogs Diagnosis and Management of Large Pituitary Tumors in Dogs With Pituitary-Dependent Hyperadrenocorticism Differential Diagnosis of Hyperkalemia and Hyponatremia in Dogs and Cats Effects of Nonadrenal Disease on Adrenal Function Tests in Dogs

Growth Hormone Therapy in the Dog Hyperadrenocorticism in the Ferret The Incidentally Discovered Adrenal Mass The Kidney and Hyperthyroidism Treatment of Insulinoma in the Dog, Cat, and Ferret Treatment of Non–Insulin-Dependent Diabetes Mellitus in Cats Using Oral Hypoglycemic Agents

169

C hapter 

38

Interpretation of Endocrine Diagnostic Test Results for Adrenal and Thyroid Disease Robert J. kemppainen, Auburn, Alabama Ellen N. Behrend, Auburn, Alabama

T

he following questions represent frequent inquiries received by our endocrine diagnostic laboratory. In previous editions of this book (Kemppainen and Zerbe, 1989; Kemppainen and Clark, 1995) protocols and interpretation of common endocrine tests were described. Reference ranges mentioned are used by the Auburn University Endocrine Diagnostic Service. Refer to the Table “Systeme International (SI) Units in Clinical Chemistry” in the Appendices for conversions between SI (e.g., nmol/L) and mass units (e.g., g/100 ml).

Adrenocorticotropic Hormone Stimulation Test I am having difficulty locating a source for adrenocorticotropic hormone (ACTH) gel. What should I do? We recommend the use of Cortrosyn (synthetic ACTH or cosyntropin, Amphastar Pharmaceuticals, Rancho Cucamonga, CA). Cortrosyn is sold in packs of 10 or as a single vial of 0.25 mg (250 mcg). The dose for dogs is 5 mcg/kg intravenously (IV) (maximal dose, 250 mcg; Kerl et al., 1999); for cats the dose is 125 mcg IV. In dogs and cats a pre-ACTH sample is collected, ACTH is injected, and one post-ACTH sample is collected 1 hour later. Recent work indicates that the 5 mcg/kg dose is equally effective in dogs when given intramuscularly (IM), using the same sampling times (Behrend et al., 2006). Once a Cortrosyn vial is reconstituted, it can be stored in the refrigerator for up to 4 months and reused. We recently tested four ACTH formulations compounded by pharmacies and sold to veterinarians (Kemppainen, Behrend, and Busch, 2005). This study, performed using healthy laboratory dogs, showed that each of these products stimulated serum cortisol to an equivalent extent, as did Cortrosyn when samples were collected at 1 hour after ACTH injection; but values at 2 hours after ACTH varied considerably. Therefore we recommend that users of compounded ACTH products collect two post-ACTH samples (at 1 and 2 hours after ACTH). To our knowledge no studies have yet assessed responses to various forms of compounded ACTH in dogs with adrenal disease, nor have possible variations in responses related to lot-to-lot differences been conducted. 170

I performed an ACTH stimulation test to evaluate a dog for Addison’s disease, and the post-ACTH cortisol value was greater than normal. Could this dog actually have hyperadrenocorticism? It’s unlikely. It is not uncommon to find a mildly-tomoderately elevated post-ACTH cortisol concentration in dogs tested for Addison’s disease (in dogs not affected by the disease). Presumably a normal physiologic response to recent (or chronic) stress is the cause of the elevation; thus we consider this response to be indicative of a normal pituitary-adrenal axis. In true cases of Addison’s disease, cortisol concentrations both before and after ACTH are usually very low (both less than 10 nmol/L). Can recent steroid therapy affect the ACTH stimulation test? Yes, glucocorticoids can affect the results in two ways. First, some glucocorticoids cross-react in the cortisol assay and can be detected as immunoreactive cortisol. In our assay, cross-reacting steroids include hydrocortisone, prednisone, and prednisolone. In general, we recommend waiting at least 12 hours after (oral) administration to allow these drugs to clear. Second, glucocorticoid therapy may suppress the pituitary-adrenal axis, causing reduced cortisol concentrations before and after ACTH administration. The severity and duration of this suppression is related to dose, potency, frequency of use, and chemical form (e.g., repositol versus oral) of the glucocorticoid therapy. I treated a dog suspected of having Addison’s disease with steroids yesterday, and now I want to perform an ACTH stimulation test. Will the results be meaningful? Yes, they probably will be useful. A single injection (or infusion) of glucocorticoids may lower the cortisol values in the ACTH stimulation test. However, this type of short-term, nonrepositol treatment will only moderately lower the cortisol values (about 25%) relative to the normal range. Most dogs with Addison’s disease have very low plasma cortisol concentrations and fail to show any increase in cortisol in response to ACTH.



Chapter  38  Interpretation of Endocrine Diagnostic Test Results for Adrenal and Thyroid Disease

How do I monitor the efficacy of mitotane therapy? Periodic ACTH stimulation testing is recommended in all dogs with hyperadrenocorticism treated with mitotane. “Ideal” cortisol concentrations in a dog receiving treatment are between 30 and 150 nmol/L in both pre- and post-ACTH samples. If values are below ideal, mitotane should be discontinued, and the dog rechecked with ACTH stimulation periodically (i.e., about every 2 to 3 weeks at first). Once values rise into the ideal range, maintenance therapy can be instituted. If values are mildly-tomoderately greater than 150 nmol/L (e.g., in the 150- to 300-nmol/L range), one should consider increasing the dose (approximately 25%) if maintenance therapy is being given or continuing daily loading therapy for a few additional days. If values are higher, it is likely that 5 to 7 days of daily mitotane will be necessary to reduce the adrenal cortical mass to the target level. Clinical condition and recurrence of signs must be considered in the choice of therapy. How long should I wait between performing a dexamethasone suppression test and an ACTH stimulation test? We suggest waiting at least 48 hours after a low dose of dexamethasone (0.01 to 0.015 mg/kg) and 5 days after a high dose of dexamethasone (0.1 to 1.0 mg/kg). No delay is necessary when performing the combined dexamethasone suppression–ACTH stimulation test (Kemppainen and Zerbe, 1989). Dexamethasone suppression tests can be performed the day after ACTH stimulation testing.

Dexamethasone Suppression Testing What form of dexamethasone should I use for a dexamethasone suppression test? Dexamethasone in polyethylene glycol or dexamethasone sodium phosphate can be used, but the dose is based on the amount of active dexamethasone in solution. For example, a 4-mg/ml solution of dexamethasone sodium phosphate provides about 3 mg/ml of active dexamethasone. The dexamethasone can be given IV or IM, although we prefer the IV route. I think I injected the dexamethasone outside the vein. What should I do? It is best to wait 48 hours (low dose) or 72 hours (high dose) and repeat the test. The calculated (low) dose of dexamethasone is only 0.03 ml for this poodle. How do I accurately administer such a small volume of dexamethasone? It is important to administer the correct dose. Dilute the dexamethasone (e.g., make a 1:20 dilution by mixing 0.2 ml of dexamethasone with 3.8 ml of sterile saline or sterile water) so that a reasonable volume is given. (For Azium, a 1:20 dilution will make the solution 0.1 mg/ml.) Can I use the results of the low-dose dexamethasone suppression test to both diagnose and differentiate hyperadrenocorticism in dogs?

171

Sometimes the results can strongly indicate a diagnosis of pituitary-dependent hyperadrenocorticism (but never adrenal-dependent hyperadrenocorticism). If the concentration in the 8-hour sample is greater than 30 nmol/L, the results are consistent with hyperadrenocorticism. If in addition the 4-hour postdexamethasone cortisol concentration is less than 30 nmol/L and/or the concentration in the 4- and/or 8-hour sample is less than 50% of the predexamethasone cortisol concentration, pituitary-dependent hyperadrenocorticism is likely.

General Questions Concerning the Diagnosis of Hyperadrenocorticism Do normal results on an ACTH stimulation test or a lowdose dexamethasone suppression test rule out hyperadrenocorticism? Conversely, do abnormal results definitely diagnose the disease? Results of the ACTH stimulation test will be in the normal range in at least 20% of dogs with hyperadrenocorticism, whereas the false-negative rate with the low-dose dexamethasone test is approximately 5%. If results of one test are normal but clinical suspicion for the disease is high, one should consider performing the other screening test. It is important to recognize that each test also has false-positives, particularly when dogs with nonadrenal disease are tested. Interestingly, of the two screening procedures the low-dose dexamethasone suppression test seems more prone to this potential error. About 50% of dogs in one study with nonadrenal illness had abnormal results (inadequate suppression of plasma cortisol) when tested with a low dose of dexamethasone (Kaplan, Peterson, and Kemppainen, 1995). None of the dogs in that study had a clinical presentation or signs consistent with hyperadrenocorticism. Assessment of test results in dogs with nonadrenal illness in which a clinical suspicion of hyperadrenocorticism is also present is challenging. The predictive value for hyperadrenocorticism of a positive screening test result increases in direct proportion to the number and severity of clinical signs and biochemical changes typically occurring in the disease. What is the best test for hyperadrenocorticism in cats? We recommend the high-dose dexamethasone suppression test, administering the steroid at a dose of 0.1 mg/kg IV and collecting a predexamethasone sample and two samples after dexamethasone administration (at 4 and 8 hours). How and why should I try to differentiate pituitary- from adrenal-dependent hyperadrenocorticism in dogs? Unless results of the low-dose dexamethasone suppression test support pituitary-dependent hyperadrenocorticism, a differentiating test is recommended. Results of ACTH stimulation testing cannot differentiate the types. The two endocrine tests for this purpose are the highdose dexamethasone suppression test (0.1 or 1.0 mg/ kg in dogs and 1 mg/kg in cats) and endogenous ACTH measurement. Timing of sample collection in the highdose–dexamethasone suppression test is the same as for the low-dose test. If cortisol concentrations at 4 and/or

172

Section  III  Endocrine and Metabolic Diseases

8 hours post dexamethasone suppress (>50% decline from baseline or decline to 25 nmol/L), it is unlikely that the dog is hypothyroid. If the T4 is less than normal, the dog may or may not be hypothyroid. Numerous nonthyroidal factors such as medications and chronic illness (i.e., euthyroid sick syndrome) can suppress T4 to less than the normal range (also see Chapter 41 for additional details about thyroid testing). What is the value of measuring free T4? Free T4 (FT4) is the portion of total T4 not bound to protein and represents about 0.1% of total T4. The pitu-

itary-thyroid axis functions to maintain free, not total, T4 within a certain range; thus measurement of FT4 is a better test of thyroid function. Two methods are used to measure FT4: analog radioimmunoassay and equilibrium dialysis. Analog radioimmunoassay is less expensive but is not reliable in dogs with euthyroid sick syndrome; it provides no additional diagnostic value over measurement of total T4 (Nelson et al., 1991). Equilibrium dialysis gives more reliable estimates of true FT4 concentrations. Measurement of FT4 can be the initial test for the diagnosis of hypothyroidism, or it can be used in dogs that have been found to have borderline-low total T4 concentrations. However, it has been demonstrated that nonthyroidal disease and therapy with certain drugs (e.g., phenobarbital, glucocorticoids) are associated with reduced FT4, even when measured using the dialysis method (Ferguson and Peterson, 1992; Kantrowitz et al, 1999, 2001). Measurement of FT4 by dialysis is more effective than total T4 in distinguishing euthyroidism from hypothyroidism. However, all of the current tests for diagnosing hypothyroidism in dogs can be influenced by nonthyroidal factors. How would I know if autoantibodies to thyroid hormones are present, and what is their significance? Autoantibodies are usually suspected when total T3 or T4 concentrations are high in a sample from a dog evaluated for hypothyroidism. With procedures used by most diagnostic laboratories, the presence of autoantibodies causes false elevations in the apparent concentration. Total T3 is most often affected; however, autoantibodies to T3 are present in less than 1% of samples submitted to our laboratory. The exact clinical and prognostic significance of autoantibodies to thyroid hormones is unknown (Kemppainen and Young, 1992). Presence of autoantibodies to T4 or T3 does not mean that a dog is hypothyroid. If autoantibodies are present, it is best to measure FT4 by equilibrium dialysis and thyroid-stimulating hormone (TSH) to better evaluate thyroid function. If the FT4 and TSH concentrations are normal, the patient should be scheduled for periodic (every 4 to 6 months) FT4 determination. If the FT4 level is low and TSH is ­elevated, hypothyroidism is likely. How valuable is measurement of endogenous canine TSH? In dogs with primary hypothyroidism, TSH concentrations are expected to be elevated because of the loss of negative feedback by thyroid hormones on the pituitary. Since about 95% of canine hypothyroidism is caused by primary thyroid failure (and not deficiency of ­pituitary TSH), measurement of TSH should be a useful test. Indeed, thyroidectomized dogs had TSH levels approximately 30 times greater than normal (Williams et al., 1996). Data obtained using the assay so far are somewhat discouraging, at least in terms of the test providing an unequivocal diagnosis of the disease. In one study of 62 normal dogs, 3 showed elevated TSH concentrations; and, although 7 of 16 spontaneously hypothyroid dogs had clearly elevated TSH levels, 3 had only marginal increases, and 6 had TSH concentrations within the normal range (Scott-Moncrieff et al., 1998).



Chapter  38  Interpretation of Endocrine Diagnostic Test Results for Adrenal and Thyroid Disease

Another concern was that 4 of 33 dogs with euthyroid sick syndrome had elevated TSH concentrations. Thus data so far suggest that concentrations of TSH are elevated in most but not all dogs with primary hypothyroidism and that approximately 10% of healthy dogs and dogs with euthyroid sick syndrome have TSH concentrations greater than currently established normal ranges. More commonly it appears that a significant number (approximately 25% to 30%) of hypothyroid dogs have normal TSH concentrations. A sole determination of endogenous TSH concentration should not be used to diagnose hypothyroidism. The test should be used to supplement historical data and clinical examination findings in conjunction with measurement of total or FT4 concentrations or both. Interestingly, concentrations of TSH appear less affected, compared with total T4, total T3, and FT4 concentrations, by nonthyroidal illness in dogs (Kantrowitz et al., 2001). The total T4 concentration in a dog suspected of having hypothyroidism is less than normal. How certain can I be that this dog is hypothyroid? A low total T4 means that the dog may be hypothyroid; alternatively a nonthyroidal factor could be depressing T4, or this dog could simply have a lower than “normal” circulating total T4 concentration (and be euthyroid). Some options available for evaluating these patients are summarized below: • FT4 (dialysis method) and TSH can be measured. These tests are more definitive than total T4. This is the best option. • Total T4 can be retested in 6 to 8 weeks. If the dog is hypothyroid, the T4 should continue to decline, and clinical signs should become more profound. • Trial thyroid hormone replacement therapy can be attempted. The dog should be reevaluated after 5 and 10 weeks of T4 therapy using objective criteria (e.g., regrowth of hair) to assess recovery. A postpill T4 level should be evaluated after 5 weeks to ensure that therapeutic and not elevated blood levels of the hormone are present. Trial therapy is complicated by partial responders and the fact that T4 may have a pharmacologic effect to induce hair growth in some euthyroid dogs. Incorrect diagnosis can consign the owner to providing lifelong therapy; thus the first two options are strongly recommended in preference to the third. How do I test for hypothyroidism when a dog is on thyroid supplementation? Trying to confirm a diagnosis of hypothyroidism after thyroid replacement therapy has been initiated can be difficult. Therapy should be withdrawn, and the pituitary-thyroid axis allowed to recover. A total T4 or better FT4 by equilibrium dialysis should be measured after 1 month. If the result is borderline, therapy should be withheld for an additional 4 weeks, and the measurement repeated to see if there is continuing recovery. The time needed to allow full recovery of thyroid gland function after chronic suppression by exogenous T4 is unknown.

173

Feline Hyperthyroidism Does the finding of a normal T4 level in a cat rule out hyperthyroidism? No. Cats with early or mild hyperthyroidism may have a T4 concentration within the upper half of the normal range (i.e., 25 to 50 nmol/L). The T4 level can fluctuate in and out of the normal range in such cats. Alternatively nonthyroidal factors (illness) can suppress the T4 level in a hyperthyroid cat into the upper half of the reference range. If the T4 level is normal but I am still suspicious of hyperthyroidism, what can I do? If the T4 level is less than 25 nmol/L, it is unlikely that the cat is hyperthyroid. If the T4 level is in the upper normal range (25 to 50 nmol/L), further evaluation is warranted. In sick, older cats with a normal thyroid function, low total T4 concentrations are typically measured (Peterson and Gamble, 1990). Options to consider in hyperthyroidsuspect cats with T4 values in the upper normal range follow: • FT4 should be measured by equilibrium dialysis (Peterson et al., 2001). • The total T4 measurement should be repeated; sometimes T4 will fluctuate into and out of the normal range in hyperthyroid cats. Alternatively tests such as T3 suppression or thyrotropin-releasing hormone stimulation can be used. What is the value of measuring FT4 in cats suspected of being hyperthyroid? The rationale of using the FT4 to diagnose hyperthyroidism in cats is the same as that for using this measurement in dogs—that the concentration of FT4 is less affected by nonthyroidal factors. In this instance FT4 should be high in hyperthyroidism. Its use seems most appropriate for cats with mild or early hyperthyroidism or in cats suspected of being hyperthyroid with nonthy­ roidal illness that have total T4 concentrations in the upper normal range (see earlier). In one study FT4 was elevated in 191 of 205 mildly hyperthyroid cats (93%) as compared with finding an elevated total T4 in 125 of these cats (61%) (Peterson et al., 2001). However, FT4 may also be elevated in up to 12% of sick, euthyroid cats (Mooney, Little, and Macrae, 1996). To help discriminate between hyperthyroidism and euthyroid sick syndrome in cats, a total T4 should be measured along with the FT4. Hyperthyroid cats tend to have total T4 concentrations in the upper half of the normal range; whereas sick, euthyroid cats have total T4 values in the lower half of the normal range, even if they show elevated FT4 (Mooney et al., 1996). The total T4 concentration in a cat I was testing for hyperthyroidism came back less than normal. Is the cat hypothyroid? It is unlikely. It is most likely that the cat has the euthyroid sick syndrome since hypothyroidism is rare in cats. Measurement of FT4 will help differentiate hypothyroidism from the euthyroid sick syndrome.

174

Section  III  Endocrine and Metabolic Diseases

References and Suggested Reading Behrend EN et al: Intramuscular administration of low-dose ACTH for ACTH stimulation testing in dogs, J Am Vet Med Assoc, 229:528, 2006. Ferguson DC, Peterson ME: Serum-free and total iodothyronine concentrations in dogs with spontaneous hyperadrenocorticism, Am J Vet Res 53:1636, 1992. Graves TK, Peterson ME: Diagnostic tests for feline hyperthyroidism, Vet Clin North Am Small Anim Pract 24:567, 1994 Kantrowitz LB et al: Serum total thyroxine, total triiodothyronine, free thyroxine, and thyrotropin concentrations in epileptic dogs treated with anticonvulsants, J Am Vet Med Assoc 214:1804, 1999. Kantrowitz LB et al: Serum total thyroxine, total triiodothyronine, free thyroxine, and thyrotropin concentrations in dogs with nonthyroidal disease, J Am Vet Med Assoc 219:765, 2001. Kaplan AJ, Peterson ME, Kemppainen RJ: Effects of disease on the results of diagnostic tests for use in detecting hyperadrenocorticism in dogs, J Am Vet Med Assoc 207:445, 1995. Kemppainen RJ, Clark TP: CVT update: sample collection and testing protocols in endocrinology. In Bonagura JD, Kirk RW, editors: Kirk’s current veterinary therapy xii: small animal practice, Philadelphia, 1995, Saunders, p 335. Kemppainen RJ, Young DW: Canine triiodothyronine autoantibodies. In Kirk RW, Bonagura JD, editors: Current veterinary therapy XI: small animal practice, Philadelphia, 1992, Saunders, p 327. Kemppainen RJ, Zerbe CA: Common endocrine diagnostic tests: normal values and interpretation. In Kirk RW, Bonagura JD, editors: Current veterinary therapy X: small animal practice, Philadelphia, 1989, Saunders, p 961.

Kemppainen RJ, Behrend EN, Busch KA: Use of compounded adrenocorticotropic hormone (ACTH) for adrenal function testing in dogs, J Am Anim Hosp Assoc 41:368, 2005. Kerl ME et al: Evaluation of a low-dose synthetic adrenocorticotropic hormone stimulation test in clinically normal dogs and dogs with naturally developing hyperadrenocorticism, J Am Vet Med Assoc 214:1497, 1999. Kintzer PP, Peterson ME: Mitotane (o,p′-DDD) treatment of cortisol-secreting adrenocortical neoplasia. In Kirk RW, Bonagura JD, editors: Current veterinary therapy X: small animal practice, Philadelphia, 1989, Saunders, p 1034. Mooney CT, Little CJL, Macrae AW: Effect of illness not associated with the thyroid gland on serum total and free thyroxine concentrations in cats, J Am Vet Med Assoc 208:2004, 1996. Nelson RW et al: Serum free thyroxine concentration in healthy dogs, dogs with hypothyroidism, and euthyroid dogs with concurrent illness, J Am Vet Med Assoc 198:1401, 1991. Peterson ME, Gamble DA: Effect of nonthyroidal illness on serum thyroxine concentrations in cats: 494 cases (1988), J Am Vet Med Assoc 197:1203, 1990. Peterson ME, Melian C, Nichols R: Measurement of serum concentrations of free thyroxine, total thyroxine, and total triiodothyronine in cats with hyperthyroidism and cats with nonthyroidal disease, J Am Vet Med Assoc 218:529, 2001. Scott-Moncrieff JC et al: Comparison of serum concentrations of thyroid-stimulating hormone in healthy dogs, hypothyroid dogs, and euthyroid dogs with concurrent disease, J Am Vet Med Assoc 212:387, 1998. Williams DA et al: Validation of an immunoassay for canine thyroid-stimulating hormone and changes in serum concentration following induction of hypothyroidism, J Am Vet Med Assoc 209:1730, 1996.

C hapter 

39

Medical Treatment of Feline Hyperthyroidism* Lauren A. Trepanier, Madison, Wisconsin

H

yperthyroidism is the most common endocrine disorder in cats, affecting approximately 2% of all cats presenting to veterinary teaching hospitals. Management options include radioiodine therapy, thyroidectomy, or medical treatment with antithyroid drugs such as methimazole. Radioiodine is considered the treatment of choice for hyperthyroidism based on its high efficacy and relative lack of complications (Table 39-1) (see Chapter 40). However, there are some situations in which methimazole therapy may be preferred over radioiodine. Methimazole is useful before thyroidectomy to normalize serum thyroxine (T4) concentrations and reduce the risk of tachyarrhythmias during anesthesia. Methimazole, which is reversible, is similarly indicated in cats with renal insufficiency, either for long-term therapy or as a “clinical test” to determine whether serum T4 can be safely lowered without causing renal decompensation. Practical considerations such as lack of a convenient referral center with a radiation license, client fears about radiation or quarantine, or initial cost to the client may also drive the use of methimazole.

Methimazole Actions, Dosing, and Efficacy Methimazole blocks thyroid hormone synthesis by inhibiting thyroid peroxidase, the enzyme involved in the oxidation of iodide to iodine, incorporation of iodine into thyroglobulin, and coupling of tyrosine residues to form T4 and triiodothyronine (T3). Methimazole does not block the release of preformed thyroid hormone, which explains the delay of 2 to 4 weeks before serum T4 concentrations fully normalize after beginning treatment in cats. Methimazole does not decrease goiter size; in fact, goiters may become larger over time despite therapy. Typical starting doses of methimazole range from 1.25 to 2.5 mg per cat twice daily (Table 39-2). More frequent dosing (three times daily) is rarely necessary. Higher doses of 5 mg two to three times daily, used in original cases of cats with relatively high serum T4 concentrations, are probably not needed for initial therapy of cats with mild-to-moderate hyperthyroidism and could potentially increase the risk of renal decompensation from a rapid fall in serum T4. Starting dosages can be titrated upward if there is an inad-

*Supported in part by grants from the Winn Feline Foundation and the University of Wisconsin-Madison Companion Animal Fund.

equate initial response to lower doses of methimazole over 2 to 4 weeks. In cats that tolerate methimazole without side effects, efficacy is greater than 90%. In humans methimazole has a long residence time in the thyroid gland and can exert antithyroid effects for 24 hours or more. Because of this, methimazole can be given once daily in humans with remission rates that are comparable to divided daily dosing. However, when our group studied 40 hyperthyroid cats we found that oncedaily dosing (5 mg) was less effective than divided dosing (2.5 mg twice daily), with only 54% of cats achieving a euthyroid state after 2 weeks of once-daily treatment compared to 87% of cats treated with divided dosing (Trepanier et al., 2003). Therefore, unless clients are unable to dose more frequently than once daily, divided twice-daily dosing of methimazole is preferred to maximize efficacy. Dosing less frequently than once daily is unlikely to be effective because serum T4 concentrations rise to pretreatment hyperthyroid values within 48 hours after discontinuing methimazole.

Methimazole Side Effects Blood Dyscrasias Methimazole can lead to neutropenia and/or thrombocytopenia in 3% to 9% of treated cats. Cats with methimazole-induced blood dyscrasias usually recover within a week of drug discontinuation. Continuing methimazole in the face of thrombocytopenia has led to clinically significant hemorrhage, including epistaxis and oral bleeding. Rechallenge with methimazole in cats with neutropenia can lead to a recurrent severe neutropenia within 1 week. Although the mechanisms for these blood dyscrasias in cats have not been established, methimazole-induced neutropenia in humans is associated with an arrest of myeloid progenitors in the bone marrow. Treatment with granulocyte-macrophage colony-stimulating factor has been advocated in human patients, but does not appear to hasten recovery in most people.

Facial Excoriation Approximately 2% to 3% of cats treated with methimazole develop excoriations of the face and neck, leading to characteristic scabbed lesions in front of the pinnae. Generalized erythema and pruritus may also occur. These excoriations are only partially responsive to glucocorticoids, and drug discontinuation is almost always required. 175

176

Section  III  Endocrine and Metabolic Diseases

Table  39-1 Advantages and Disadvantages of Major Therapies for Feline Hyperthyroidism Treatment

Advantages

Disadvantages

Radioiodine

>90% efficacy Single injection Few side effects (rare dysphagia) Curative ≈90% efficacy Curative

High initial expense Somewhat limited availability Irreversible

Thyroidectomy

Methimazole

Low initial expense ≈90% efficacy in cats that do not have side effects Reversible

High initial expense Anesthetic risks Risk of hypoparathyroidism Risk of recurrent laryngeal nerve damage Irreversible Daily drug administration Drug side effects

Table  39-2 Drugs Useful in the Medical Management of Hyperthyroidism Drug

Indications

Dosage

Side effects

Comments

Methimazole

Hyperthyroid cats with azotemia or for clients declining radioiodine

1.25-5 mg per cat twice daily (start at lower end)

Transdermal route has fewer GI side effects

Carbimazole

Prodrug of methimazole

2.5-5 mg per cat twice daily

GI upset Facial excoriation Blood dyscrasias Hepatopathy GI upset Facial excoriation Blood dyscrasias Hepatopathy

Iopanoic acid or calcium ipodate

Adjunct control of T3 in cats intolerant of methimazole Unclear if useful for cats intolerant of methimazole Control of tachyarrhythmias or hyperactivity Adjunct control of T3 in cats intolerant of full dosages of methimazole Control of tachyarrhythmias or hyperactivity

100-200 mg per day (empiric)

Propylthiouracil

Propranolol

Atenolol

Inhibits conversion of T4 to T3 Effects may be transient

25 mg per cat twice daily Hemolytic anemia (empiric) Thrombocytopenia Bleeding diathesis 2.5-5 mg per cat three Bronchoconstriction in times daily cats with prior lower airway disease

Enalapril or benazepril

Control of hypertension

0.5 mg/kg once or twice daily

Sinus bradycardia AV block in susceptible cats Lethargy Inappetence

Amlodipine

Control of moderate-tosevere hypertension

0.625 mg per cat once daily

Lethargy Inappetence

GI, Gastrointestinal; T3 , triiodothyronine; T4 , thyroxine.

3.125-6.25 mg per cat twice daily

Not recommended in cats intolerant of methimazole

Inhibits conversion of T4 to T3

Selective β1- blocker Potential effect of limiting glomerulosclerosis in cats with renal disease Benazepril does not accumulate in renal failure Drug of choice for severe hypertension



Chapter  39  Medical Treatment of Feline Hyperthyroidism

Pruritus has also been reported in human patients treated with methimazole, but the mechanisms for these reactions have not been explored.

Hepatotoxicity Increases in serum alkaline phosphatase (SAP) and bilirubin, or alanine aminotransferase (ALT), are observed in approximately 2% of cats treated with methimazole (Peterson, Kintzer, and Hurvitz, 1988); liver biopsy may show hepatic necrosis and degeneration. Liver enzyme elevations are usually reversible over several weeks following drug discontinuation, although nutritional and fluid support may be required. Rechallenge can lead to recurrent hepatopathy, and future drug avoidance is generally recommended. In rodent models methimazole hepatotoxicity is exacerbated by glutathione depletion (Mizutani et al., 1999). The role of glutathione depletion, or supplementation, in methimazole-associated hepatotoxicity in cats has not been evaluated.

Simple Gastrointestinal Upset Anorexia, vomiting, and lethargy are seen in approximately 10% of cats treated with methimazole. Simple gastrointestinal (GI) upset is most common in the first 4 weeks of treatment and can resolve with a dosage reduction. These signs may be caused in part by direct gastric irritation from the drug, since transdermal administration of methimazole is associated with significantly fewer GI side effects than the oral route (Sartor et al., 2004).

Renal Decompensation Cats with hyperthyroidism have abnormally high glomerular filtration rates (GFRs), and treating hyperthyroidism by any method leads to decreases in GFR in most hyperthyroid cats. New onset azotemia is observed in 15% to 20% of hyperthyroid cats after normalization of serum T4. Although these biochemical changes are generally clinically silent, occasional cats develop signs of illness referable to underlying renal disease. Because methimazole treatment is reversible, it is the preferred approach for initial treatment of hyperthyroid cats with preexisting azotemia to determine whether normalization of serum T4 will lead to unacceptable renal decompensation.

Coagulation Abnormalities Methimazole and to a lesser extent propylthiouracil (PTU) inhibit vitamin K–dependent clotting factor activation (γ-carboxylation) and epoxide reductase (necessary for vitamin K recycling, and the same enzyme targeted by warfarin) at high concentrations. In a study of 20 hyperthyroid cats treated with methimazole, there were no significant changes in prothrombin time or activated partial thromboplastin time, but one cat developed a prolonged protein-induced by vitamin K antagonism (PIVKA) clotting time (Randolph et al., 2000). No cats had clinically significant bleeding. This suggests a possible but apparently uncommon “warfarin-like” effect of methimazole in cats. This reaction is rare enough not to warrant routine moni-

177

toring but should be considered in any cat presenting with hemorrhage that is also being treated with methimazole.

Acquired Myasthenia Gravis Another apparently rare side effect of methimazole in cats is the development of acquired myasthenia gravis. Neuromuscular weakness, along with antibodies to the acetylcholine receptor, has rarely been reported in cats treated with methimazole. Cats have responded to either drug discontinuation or the addition of prednisone to the methimazole treatment regimen. Although this does not appear to be a side effect of methimazole in humans, hyperthyroidism itself can copresent with myasthenia in humans; in one human patient methimazole therapy was thought to worsen the clinical signs of myasthenia.

Clinical Monitoring Based on the spectrum of possible adverse reactions to methimazole, clinical monitoring at 2 to 3 and 4 to 6 weeks of treatment should include a complete blood count, ALT and SAP, and blood urea nitrogen and creatinine, in addition to serum T4. In a cat with an apparent adverse reaction to methimazole, it is important to differentiate simple GI upset (for which a lower dose or a switch to transdermal methimazole may be curative) from blood dyscrasias or hepatopathy, for which methimazole should be discontinued. Therefore this same workup should also be performed if a cat becomes clinically ill during methimazole treatment. It is also important to measure renal function and T4 simultaneously during methimazole therapy to determine whether a cat’s kidneys can tolerate the level of GFR associated with normal thyroid function. If a cat becomes newly azotemic with clinical signs, the dosage of methimazole can be titrated to maintain the serum T4 in the high high-normal range, with additional use of drugs to control hypertension and tachyarrhythmias (see Management of Hypertension).

Transdermal Methimazole Methimazole is available through custom compounding pharmacies in a transdermal formulation in pluronic lecithin organogel (PLO). PLO acts as a permeation enhancer to allow drug absorption across the stratum corneum. Although methimazole in PLO has been shown to have poor absorption in cats after a single dose, chronic dosing in hyperthyroid cats is effective in lowering serum T4 concentrations. Methimazole in PLO is applied to the cat’s inner pinna, alternating ears with each dose. Owners wear examination gloves or finger cots during administration and are instructed to remove crusted material with a moistened cotton ball before the next dose. Transdermal methimazole had significantly fewer GI side effects (4% of cats) compared to oral methimazole (Sartor et al., 2004). When our group compared these methods, there were no differences between routes in the incidence of facial excoriation, neutropenia, thrombocytopenia, or hepatotoxicity. However, transdermal methimazole was associated with somewhat lower efficacy by 4 weeks

178

Section  III  Endocrine and Metabolic Diseases

(only 67% euthyroid) compared to oral methimazole (82% euthyroid). This may be due to the result of lower bioavailability of the transdermal formulation. Drawbacks of methimazole in PLO include erythema at the dosing site in some cats, increased formulation costs, and unproven drug stability beyond 2 weeks. However, methimazole in PLO appears to be effective (anecdotally) beyond 2 weeks. I recommend that serum T4 values be checked toward the end of a 2-month prescription of the transdermal formulation to confirm that thyroid control persists.

Administration of Methimazole Before Pertechnetate Scanning or Radioiodine Therapy Because methimazole does not inhibit iodide uptake by the thyroid, concurrent methimazole therapy does not impair technetium 99m (99mTC)–pertechnetate thyroid scanning in hyperthyroid cats and in fact may enhance imaging (Fischetti et al., 2005, Nieckarz and Daniel, 2001). However, methimazole does inhibit iodine organification, which may decrease the contact time of radioiodine within the thyroid. Humans given methimazole up to 4 days before radioiodine show no differences in outcome, but administration of methimazole immediately before or after radioiodine has been associated with poorer responses. In hyperthyroid cats retrospective studies have found no association between the time of methimazole discontinuation before radioiodine and long-term radioiodine efficacy (Chun et al., 2002, Forrest et al., 1996). However, without data from a prospective randomized study, discontinuation of methimazole before radioiodine therapy is still recommended. The 1- to 2-week washout period for methimazole recommended by many radioiodine facilities may be longer than necessary but is based on efficacy data from the largest case series published (Peterson and Becker, 1995).

Management of Hypertension The prevalence of hypertension in hyperthyroid cats is reported to be 5% to 22%, and many cats with hypertension have concurrent azotemia. Normalizing serum T4 may not significantly control blood pressure in the first weeks of therapy. Therefore direct management of moderate-to-severe hypertension is indicated along with antithyroid treatment. Commonly used antihypertensive agents include amlodipine, β-blockers, and the angiotensin-converting enzyme (ACE) inhibitors. There is one small clinical trial that has demonstrated a relatively poor response to atenolol in cats in terms of achieving blood pressure control. In cases of moderate to severe hypertension, or when hypertension is associated with target organ injury, amlodipine (starting dose of 0.625 mg PO per cat once or twice daily) is most likely to lower blood pressure effectively. β-blockers such as atenolol are useful if signs of hyperactivity or tachyarrhythmias are present (see Table 39-2). ACE inhibitors such as enalapril or benazepril (0.5 mg/kg once daily) have the potential benefit of reducing intraglomerular pressure in patients with renal disease. However, ACE inhibitors are inferior to amlodipine in control of moderate to severe hypertension.

In those cats in which renoprotective effects of an ACE inhibitor are desired, combination therapy with an ACE inhibitor should be considered (see Chapter 197). In cats with overt azotemia, benazepril, which does not accumulate in renal insufficiency, is preferred by the author over enalapril. In some hyperthyroid cats without initial hypertension, hypertension can actually develop several months after treatment for hyperthyroidism, possibly as a result of unmasking of underlying renal insufficiency. Therefore rechecking cats for hypertension 2 to 3 months after restoration of a euthyroid state is indicated.

Other Antithyroid Drug Options Propylthiouracil PTU was the first drug used in the management of hyperthyroid cats in the early 1980s. This drug required high dosages (e.g., 50 mg two to three times daily) to normalize serum T4 concentrations. PTU was associated with an unacceptably high incidence of adverse events, including positive ANA, Coombs’-positive hemolytic anemia, and thrombocytopenia with bleeding diathesis. Methimazole and PTU share structural similarities; and patients with blood dyscrasias, hepatopathy, or facial excoriation during methimazole treatment may well have similar adverse reactions to PTU. However, the degree of cross-reactivity has not been critically examined in cats.

Carbimazole Carbimazole is a substituted derivative of methimazole that is a prodrug of methimazole. Carbimazole is used in the United Kingdom for treating cats with hyperthyroidism, and there are anecdotal reports that side effects are less common with carbimazole than with methimazole. This may be related to the fact that plasma methimazole concentrations are approximately 50% lower with carbimazole compared to an identical dose of methimazole. There are no definitive studies comparing the side effect rates of methimazole to carbimazole; and, because carbimazole is converted into methimazole, its use in cats with adverse reactions to methimazole is probably ill advised.

β-Blockers β-Blockers can reduce the “sympathetic overdrive” characteristic of hyperthyroidism, including tachycardia, arrhythmias, hyperactivity, and aggression. Propranolol has the additional potential benefit of inhibiting the conversion of T4 to T3 (see Table 39-2) and may be useful for the short-term management of cats intolerant of methimazole before radioiodine or thyroidectomy. However, as a nonselective β-blocker propranolol can lead to bronchospasm in susceptible cats, and may require three-times daily dosing. Atenolol, a selective β1-blocker, is not associated with bronchospasm and is preferred for β1-blockade in cats with a prior history of reactive airway disease. Because neither of these treatments normalizes serum T4 or prevents weight loss, these drugs alone are not appropriate for long-term management of hyperthyroidism. It should be noted that some cats develop a relatively slow



Chapter  39  Medical Treatment of Feline Hyperthyroidism

sinus rhythm or even sinus bradycardia after a euthyroid state is achieved, and the dosage of the beta blocker may need to be reduced or the drug discontinued. Some old cats also have atrioventricular conduction disease as a comorbid condition (likely from conduction system degeneration), and beta blockers can result in AV block in susceptible cats. Since atenolol is water soluble and therefore eliminated by renal mechanisms, both heart rate and daily dosage should be reevaluated in cats that develop renal failure following a reduction of serum T4.

Iodinated Contrast Agents Iodinated contrast agents such as ipodate and iopanoic acid inhibit conversion of T4 to T3 and have been advocated for use in hyperthyroid cats that do not tolerate methimazole (Murray and Peterson, 1997). Ipodate (Oragrafin; 308 mg of iodine per 500 mg of calcium ­ ipodate) is no longer marketed, but iopanoic acid (Telepaque; 333 mg of iodine per 500 mg of iopanoic acid) and diatrizoate meglumine (Gastrografin; 370 mg of iodine per milliliter) have been used anecdotally in hyperthyroid cats at comparable doses. Cats may respond initially with decreases in serum T3 and clinical improvement. However, long-term control is likely to be poor since the effects of these agents are often transient. All iodine-containing agents interfere with thyroid scanning and radioiodine therapy. In humans iopanoic acid must be discontinued 2 weeks before radioiodine therapy, with most patients having a normalized thyroid scan and response to radioiodine by then. Similar data are not available for cats.

References and Suggested Reading Becker T et al: Effects of methimazole on renal function in cats with hyperthyroidism, J Am Anim Hosp Assoc 36:215, 2000. Chun R et al: Predictors of response to radioiodine therapy in hyperthyroid cats, Vet Radiol Ultrasound 43:587, 2002.

179

Fischetti AJ et al: Effects of methimazole on thyroid gland uptake of 99mTC-pertechnetate in 19 hyperthyroid cats, Vet Radiol Ultrasound 46:267, 2005. Forrest L et al: Feline hyperthyroidism: efficacy of treatment using volumetric analysis for radioiodine dose calculation, Vet Radiol Ultrasound 37:141, 1996. Hoffmann G et al: Transdermal methimazole treatment in cats with hyperthyroidism, J Feline Med Surg 5:77, 2003. Mizutani T et al: Metabolism-dependent hepatotoxicity of methimazole in mice depleted of glutathione, J Appl Toxicol 19:193, 1999. Murray LA, Peterson ME: Ipodate treatment of hyperthyroidism in cats, J Am Vet Med Assoc 211:63, 1997. Nieckarz JA, Daniel GB: The effect of methimazole on thyroid uptake of pertechnetate and radioiodine in normal cats, Vet Radiol Ultrasound 42:448, 2001. Peterson ME, Becker DV: Radioiodine treatment of 524 cats with hyperthyroidism, J Am Vet Med Assoc 207:1422, 1995. Peterson ME, Kintzer PP, Hurvitz AI: Methimazole treatment of 262 cats with hyperthyroidism, J Vet Intern Med 2:150, 1988. Randolph JF et al: Prothrombin, activated partial thromboplastin, and proteins induced by vitamin K absence or antagonists’ clotting times in 20 hyperthyroid cats before and after methimazole treatment, J Vet Intern Med 14:56, 2000. Sartor LL et al: Efficacy and safety of transdermal methimazole in the treatment of cats with hyperthyroidism, J Vet Intern Med 18:651, 2004. Trepanier LA et al: Efficacy and safety of once versus twice daily administration of methimazole in cats with hyperthyroidism, J Am Vet Med Assoc 222:954, 2003.

C hapter 

40

Radioiodine for Feline Hyperthyroidism Mark E. Peterson, Bedford Hills, New York

H

yperthyroidism is the most common endocrine disorder in cats, most frequently associated with adenomatous hyperplasia (or adenoma) involving one or both thyroid lobes. Because the pathogenesis of hyperthyroidism in cats is not known, treatment of the condition is directed at controlling the excessive secretion of thyroid hormone from the adenomatous thyroid gland. Treatment options include administration of ­antithyroid drugs (see Chapter 39), surgical removal of adenomatous thyroid tissue, and administration of radioiodine. Although each of these treatment options has its advantages and disadvantages, the use of radioiodine is considered by most authorities to be the treatment of choice for most hyperthyroid cats. Radioactive iodine provides a simple, effective, and safe treatment for cats with hyperthyroidism. It is a particularly useful treatment for cats with bilateral thyroid involvement (found in approximately 70% of cats), cats with ectopic (intrathoracic) thyroid tissue, and the rare feline patient with thyroid carcinoma. Treatment with radioiodine avoids the inconvenience of daily oral administration and side effects associated with antithyroid drugs, as well as the risks and postoperative complications associated with anesthesia and surgical thyroidectomy. Although the therapy is simple and relatively stress free for cats, it does require special licensing and hospitalization facilities, nuclear medicine equipment, and extensive compliance with local and state radiation safety laws. The purpose of this chapter is to give an overview of aspects of radioiodine treatment germane to the practicing veterinarian who is referring hyperthyroid cats for this treatment.

Advantages of Radioiodine for Treatment of Hyperthyroidism Medical treatment with methimazole is effective in controlling hyperthyroidism in most cats, but for several reasons it may not be the best choice. First, some cats are difficult or impossible to medicate (antithyroid drugs must be administered orally or transdermally, generally one to three times daily). Second, mild reactions (e.g., loss of appetite, vomiting) are common, and a few cats develop serious untoward reactions to the antithyroid drugs (e.g., thrombocytopenia, leukopenia, hepatopathy). Because of the potential for these side effects, periodic blood tests (including complete blood and platelet counts) are necessary to monitor the cat’s condition (see Chapter 39). Finally, some owners may not want to have to medicate 180

their cat on a daily basis for the rest of the cat’s life, especially if the cat is only middle-aged. Surgery is an effective treatment for hyperthyroidism in most cats but may have disadvantages. Many cats with hyperthyroidism have secondary cardiomyopathy and are higher surgical and anesthetic risks; therefore preoperative preparation of hyperthyroid cats with antithyroid drugs ~    or β−adrenergic blocking agent (or concurrent administration of both drugs) is generally recommended. There is also a risk that there will be damage to the adjacent parathyroid glands during thyroid surgery, resulting in transient or, less commonly, permanent hypoparathyroidism and hypocalcemia. This complication can be life threatening and results in extra hospitalization and cost. After surgery cats may occasionally develop hypothyroidism (usually transient), necessitating treatment with thyroid hormone replacement. Finally, there is always the potential that the hyperthyroidism will not be cured with surgical treatment or that the condition will recur a few months to years after successful thyroidectomy. The prevalence that hyperthyroidism will persist or recur is higher among cats that have only one thyroid lobe removed at time of surgery because most cats have adenomatous hyperplasia involving both thyroid lobes. In addition, there is always a chance that one or both of the cat’s adenomatous thyroid lobes has descended ventrally below the thoracic inlet or that the cat has hyperfunctional thyroid tissue at ectopic sites. In either case such intrathoracic or ectopic thyroid tissue may be difficult to resect surgically. Radioiodine therapy has some distinct advantages over use of medical or surgical treatment. Overall, radioiodine provides a simple, effective, and safe treatment for cats with hyperthyroidism. With radioiodine the need for anesthesia and the risk of hypoparathyroidism (the major disadvantages with surgery) are eliminated. Antithyroid drug treatment is not needed; in fact, many treatment centers recommend that drug treatment must be discontinued for a short time (usually 1 to 2 weeks) before radioiodine is administered to the cats because lower doses of radioiodine may be needed. The administered radioactive iodine concentrates in and destroys hyperactive thyroid tissue within the cat’s body, whether in the normal cervical area or in ectopic sites.

Disadvantages of Radioiodine Treatment As with other major forms of treatment, there are a few disadvantages to the use of radioiodine in cats with

hyperthyroidism. This treatment is not universally available and requires complete knowledge of radiation safety and the use of expensive and sophisticated equipment. The major drawback is that, after administration of radioiodine, the cat must be kept hospitalized for a specified period (7 to 10 days in most treatment centers) and visitation is not allowed. Because of the relatively long isolation period away from the owner, some cats do become depressed; however, it is much more common for the owners to complain of their emotional distress. Most cats tend to do well during the boarding period. As with any therapy, radioiodine treatment is not perfect. A few cats (< 5%) may not respond adequately to a single treatment, thus requiring retreatment at a later time. Although the reason for such initial treatment failures is not always clear, most of these cats respond well to the second treatment with resolution of their hyperthyroidism.

Mechanism of Action of Radioiodine Treatment Thyroid hormones are the only iodinated organic compounds in the body. Therefore the only function of ingested iodine is for thyroid hormone synthesis. Ingested stable iodine (127I) is converted to iodide in the gastrointestinal tract and absorbed into the circulation. In the thyroid gland iodide is concentrated or trapped by active transport mechanisms of the thyroid follicular cell, resulting in intracellular iodide concentrations that are 10 to 200 times that of serum. Once inside the thyroid cell, iodide is oxidized to iodine, which is incorporated into tyrosine residues of thyroglobulin (organification) to form the thyroid hormones thyroxine (T4 ) and 3,5,3¢ triiodothyronine. The radioisotope used to treat hyperthyroidism is radioiodine-131 (131I). The basic principle behind treatment of hyperthyroidism with 131I is that thyroid cells do not differentiate between stable and radioactive iodine; therefore radioiodine, like stable iodine, is concentrated by the thyroid gland after administration. In cats with hyperthyroidism, radioiodine is concentrated primarily in the hyperplastic or neoplastic thyroid cells, where it irradiates and destroys the hyperfunctioning tissue. Normal thyroid tissue tends to be protected from the effects of radioiodine since the uninvolved thyroid tissue is suppressed and receives only a small dose of radiation (unless very large doses are administered). When administered to a cat with hyperthyroidism, a large percentage of radioiodine accumulates in the thyroid gland (i.e., most cats extract between 20% to 60% of the administered radioiodine dose from the circulation). The remainder of the administered 131I is excreted primarily in the urine and to a lesser degree the feces. 131 -I has a half-life of 8 days and emits both β-particles and γ-radiation. The β-particles, which cause 80% of the tissue damage, travel a maximum of 2 mm in tissue and have an average path length of 400 μm. Therefore β-particles are locally destructive but spare adjacent hypoplastic thyroid tissue, parathyroid glands, and other cervical structures.

Chapter  40  Radioiodine for Feline Hyperthyroidism

181

Patient Selection and Preparation Before Radioiodine Treatment Routine diagnostic testing generally should be performed by the referring veterinarian before referral for radioiodine treatment to determine if the cat is an appropriate candidate for this treatment. This is very important, inasmuch as these cats tend to be middle- to old-aged and therefore may have other geriatric problems unrelated to the cat’s hyperthyroidism. Cats should be relatively stable before being considered for radioiodine therapy. Cats that have clinically significant cardiovascular, renal, gastrointestinal, endocrine (e.g., diabetes), or neurologic disease may not be very good candidates for this treatment, especially because of the length of boarding required after the 131I treatment is administered. The recommended pretreatment workup generally should include the following tests: • Routine database, including a complete blood count, serum chemistry panel, and urinalysis • Pretreatment or untreated serum total T4 concentration (not on antithyroid drug treatment); if the cat has been treated antithyroid for longer than 1 to 2 months, the antithyroid medication might have be discontinued for 5 to 7 days, and another serum total T4 determined to determine the true severity of the cat’s hyperthyroidism • Chest radiography or cardiac ultrasonography or both should be performed if cat has evidence of any clinically significant cardiac disease (especially pronounced heart murmur, arrhythmia, dyspnea, or jugular venous distension) Determination of a pretreatment free T4 concentration alone (without a total T4concentration) is generally not acceptable for referral for radioiodine treatment. It is clear that determination of free T4 concentrations can be very useful in diagnosis of hyperthyroidism, especially in cats in which the disease is suspected but the total T4 concentration remains within normal range. However, because a high free T4 concentration also develops in some sick cats that do not have hyperthyroidism and certainly would not benefit from radioiodine treatment, the diagnosis of hyperthyroidism should never be based solely on the finding of a high free T4 concentration alone. When a free T4 determination is performed as a diagnostic test for hyperthyroidism, it must always be performed together with a total T4 concentration. If concurrent renal disease is suspected or known to be present, many recommend evaluating medical management before a more definitive means of treatment such as radioiodine. In these cats a low starting dose (i.e., 1.25 mg orally once daily) of methimazole with gradual dosage escalation is prudent, with monitoring (e.g., biochemical profile and total serum T4 determination) and dose adjustments done every 2 weeks. Based on studies regarding changes in glomerular filtration rate (GFR) associated with treatment of hyperthyroidism, it appears that maintenance of euthyroidism for 1 month without azotemia should be sufficient to decide whether to proceed with definitive therapy. Once a cat has stabilized, radioactive iodine could be considered.

182

Section  III  Endocrine and Metabolic Diseases

The veterinarian may choose to stabilize some cats for a few weeks or months before time of referral for radioiodine treatment by administering cardiovascular medications, β-blocking agents, or antithyroid drugs (see Chapter 39). Although concurrent administration of β−blocking agents does not interfere with radioiodine treatment, one should realize that prior or concurrent antithyroid drug treatment may influence the effectiveness of the radioiodine treatment, resulting in treatment failure. The effect of prior methimazole treatment on eventual outcome of radioactive iodine therapy in cats is controversial, however; and it has been variably suggested to worsen, enhance, or have no effect on radioiodine treatment. The thyroidal uptake of radioiodine is enhanced in healthy cats after recent methimazole withdrawal, and this shortterm rebound effect may be potentially beneficial when treating hyperthyroidism in cats with radioactive iodine. Some have theorized that this enhanced thyroidal uptake of radioiodine therapy may lead to a higher incidence of radioiodine-induced hypothyroidism. However, other studies have shown that discontinuing methimazole for less than or greater than 5 days before radioactive iodine therapy has no effect on treatment outcome. Overall, if antithyroid drugs have been administered, most treatment centers recommend that they be discontinued for at least 1 week before treatment with radioiodine. In some cats with severe, life-threatening hyperthyroidism or concurrent disease (e.g., renal failure), one may decide that is not wise to stop antithyroid drug treatment but to treat with antithyroidal drugs while the cat is still receiving the radioiodine administration. Such cases must be discussed with the radioiodine treatment center before the referral.

Estimation of the Radioiodine Dose to Administer Ideally administration of radioiodine restores euthyroidism with a single dose without inducing hypothyroidism. Numerous methods to calculate the administered radioiodine dose to cats with hyperthyroidism have been described, but the optimal method for determining the amount of radioactivity required for effective treatment in cats remains somewhat controversial. The reported methods used to calculate the radioiodine dose are quite variable but can be divided into three different methodologies. The first method of determining the proper dose is to use tracer kinetic studies to estimate the percentage of iodine uptake and rate of disappearance from the gland and thyroid imaging to estimate the weight of the gland; the dose of radioiodine is then calculated from these measurements. Although this method of dose determination theoretically should produce the best results, measurement of the biologic half-life of iodine in hyperthyroid cats using tracer techniques has been shown to be a poor predictor of the biologic half-life of iodine following radioiodine therapy. Presumably this discrepancy originates with the changes in thyroid physiology that develop following the delivery of large doses of radiation to the thyroid gland. As a result, there can be a marked difference between the calculated dose of radioiodine and the actual

dose delivered to the cat’s thyroid tissue. Because of this poor correlation, most centers that treat hyperthyroid cats with radioiodine no longer calculate the cats’ radioiodine doses based on measurements of the biologic halflife and uptake of iodine. A second method of treating hyperthyroid cats is to administer a fixed, relatively high dose of radioiodine to all cats (i.e., 4 mCi or 5 mCi), regardless of the severity of hyperthyroidism or size of the thyroid tumor. To accomplish a reasonable success rate, the fixed dose method uses a radioiodine dose (4 to 5 mCi) that is above the median dose reported (3 mCi) for individualized dosing methods. As a result, a large number of cats treated using this method receive excessive amounts of radioiodine exposing both the patient and veterinary personnel to unnecessary levels of radiation. Although this method is the simplest, use of this approach results in undertreatment of a few cats with severe disease but more commonly overtreatment of a number of cats with mild disease. In the third method of dose determination the dose of radioiodine administered to hyperthyroid cats is determined on the basis of a scoring system that takes into consideration the severity of clinical signs, the size of the cat’s thyroid gland (based on either physical palpation or results of thyroid imaging, and the serum T4 concentration. Using this scoring system, a low, medium, or relatively high 131I dose is selected without determining thyroid gland kinetics. For example, cats with mild clinical signs, small thyroid tumors, and only slightly high serum T4 concentrations would receive smaller doses of radioiodine (e.g., 3 mCi); cats with severe clinical signs, very large thyroid tumors, and markedly high serum T4 concentrations would receive high doses of radioiodine (i.e., 5-6 mCi); and cats that lie between these extremes would receive intermediate doses of radioiodine (e.g., 4 mCi). This approach has been shown to provide treatment results comparable to those obtained when thyroid kinetics were determined (i.e., the first method of dose determination). The major advantage of this method is that nuclear medicine equipment is not needed, the time required to determine thyroid kinetics is eliminated, and sedation of the cat is not required. In addition, in contrast to the fixed dose method, the total radiation dosage delivered to the cats with mild hyperthyroidism was minimized since lower doses are given to these cats. Radioiodine can be administered to cats intravenously or orally, but the subcutaneous route is preferred. The subcutaneous route has been shown to be equally as effective as the other routes of administration, not associated with gastrointestinal side effects, and safer for personnel, In addition, the dose can usually be administered with no or only light sedation, thereby avoiding anesthesia. In cats with thyroid carcinoma (incidence 2 positive blood cultures • >3 with common skin contaminant Minor Criteria • Fever • Medium to large dog (>15 kg) • Subaortic stenosis • Thromboembolic disease • Immune mediated disease • Polyarthritis • Glomerulonephritis • Positive blood culture not meeting major criteria • *Bartonella serology >1:1024 • No pathologic evidence Diagnosis Definite • Pathology of valve • Two major criteria • 1 major and 2 minor Possible • 1 major and 1 minor • 3 minor Rejected • Firm alternative Dx • Resolution 75%, >90%, >90%, respectively). According to the resistance profiles of ­bacteria cultured from patients within our hospital, many bacteria are resistant to ampicillin, and empiric use of ampicillin cannot be ­recommended ­without an MIC. The treatment of choice for Bartonella infections has not been defined in human or veterinary medicine. MICs are not indicative of therapeutic efficacy of antibiotics against intracellular bacteria, including Bartonella, and minimum bactericidal concentration may be more appropriate. In an in vitro study only gentamicin and not ciprofloxacin, streptomycin, erythromycin, ampicillin, or doxycycline exerted bactericidal activity against Bartonella (Rolain et al., 2000). Treatment with at least 2 weeks of aminoglycosides has been shown to improve survival in humans with Bartonella IE (Raoult et al., 2003). Current treatment recommendations in humans include aminoglycosides and β-lactam antibiotics for 4 to 6 weeks (Baddour et al., 2005). In 24 dogs with various systemic manifestations secondary to bartonellosis, treatment with the following anti­biotics resulted in clinical recovery and negative posttreatment titers: doxycycline, azithromycin, enrofloxacin, and ­amoxicillin/clavulanate (Breitschwerdt et al., 2004). In dogs with severe life-threatening IE caused by Bartonella, aggressive treatment with ­aminoglycosides

may be ­necessary, with careful ­monitoring of renal enzymes and supportive intravenous fluid administration. Azithromycin achieves high intracellular concentrations and may be given with careful monitoring of the hepatic enzymes since it may cause hepatotoxicity with chronic therapy. Anticoagulant therapy is not currently recommended since there has been a trend of increased bleeding episodes and no benefit in vegetation resolution or reduced embolic events in humans with IE treated with aspirin (Baddour et al., 2005).

Treatment of CHF Dogs with CHF should be treated with furosemide at the appropriate dose, depending on severity of pulmonary edema (stable mild-to-moderate CHF, 1 to 4 mg/kg orally [PO] BID-TID; acute fulminant CHF, 5 to 8 mg/kg intravenously [IV] q 2–4h initially and then reduced according to patient’s response). In dogs with significant aortic insufficiency secondary to aortic IE or massive mitral regurgitation, afterload reduction using amlodipine, hydralazine, or nitroprusside should be instituted providing the dog is not hypotensive at baseline. Aggressive afterload reduction in hypertensive patients is warranted. In normotensive animals the target reduction of blood pressure from baseline is 10 to 15 mm Hg. Adjunctive therapy for chronic CHF includes an angiotensin-converting enzyme inhibitor and possibly digoxin if there is myocardial failure (see Chapter 171). Antiarrhythmic treatment may be necessary, especially if there are high-grade ventricular arrhythmias (see Chapter 162).

Follow-up In patients with initially positive cultures (blood or urine), repeat culture is recommended 1 to 2 weeks after ­starting antibiotic therapy and 2 weeks following ­termination of antibiotic therapy. An echocardiogram should be ­performed after 2 weeks of antibiotic treatment, in 4 to 6 weeks, and 2 weeks following termination of antibiotic therapy to assess size of vegetative lesion and severity of valvular insufficiency. In patients affected with Bartonella, repeat serology should be performed a month after initiation of treatment, and titers should be reduced. If titers are elevated persistently, a different antibiotic may be needed.

Prophylaxis In dogs with congenital heart disease, in particular subaortic stenosis, perioperative parenteral antibiotics such as a β-lactam or a cephalosporin should be given 1 hour before surgery or dentistry and 6 hours after the procedure. Clindamycin may be useful as a prophylactic antibiotic for dental procedures. Prophylactic antibiotics for dogs with myxomatous valve degeneration undergoing a dental procedure is controversial since these dogs are not at an increased risk for development of IE; however, ­bacteremia does occur, and other tissues may be at risk.

Chapter  173  Infective Endocarditis

791

Prognosis Dogs with aortic IE have a grave prognosis, and median survival in one study was only 3 days compared to a median survival of 476 days for dogs with mitral IE (MacDonald et al., 2004). Dogs with Bartonella IE have short survival times since the aortic valve is almost exclusively affected. Similarly, in another case series 33% of dogs with aortic IE died within the first week, and 92% died within 5 months of diagnosis (Sisson, 1984). Glucocorticoid administration before treatment of IE is associated with higher mortality in dogs with IE (Calvert, 1982). Short-term death is most often caused by CHF or sudden death. Likewise, in humans with IE the presence of CHF has the greatest impact on poor prognosis. Other causes of death in dogs with IE within the first week of treatment include renal failure, pulmonary hemorrhage, and severe neurologic disease. (Acknowledgement: Dr. Valerie Wiebe, PharmD [Pharmacy], for assistance with antibiotic recommendations and Dr. Barbara Byrne, DVM [Microbiology], for MIC data, University of California Davis, Veterinary Medical Teaching Hospital.)

References and Suggested Reading Baddour LM et al: Infective endocarditis: diagnosis, antimicrobial therapy, and management of complications, AHA scientific statement, Circulation 111:e394, 2005. Barker CW et al: Pharmacokinetics of imipenem in dogs, Am J Vet Res 64:694, 2003. Breitschwerdt EB et al: Sequential evaluation of dogs naturally infected with Ehrlichia canis, Ehrlichia chaffensis, Ehrlichia equi, Ehrlichia ewingii, or Bartonella vinsoniii, J Clin Microbiol 36:2645, 1998. Breitschwerdt EP et al: Clinicopathological abnormalities and treatment response in 24 dogs seroreactive to Bartonella vinso­ nii (berkhoffii) antigens, J Am Anim Hosp Assoc 40:92, 2004. Calvert CA: Valvular bacterial endocarditis in the dog, J Am Vet Med Assoc 180:1080, 1982. Fournier PE et al: Value of microimmunofluorescence for diagnosis and follow-up of Bartonella endocarditis, Clin Diagn Lab Immunol 9:795, 2002. Houpikian P, Raoult D: Blood culture-negative endocarditis in a reference center, etiologic diagnosis of 348 cases. Medicine 84:162, 2005. MacDonald KA et al: A prospective study of canine infective endocarditis in northern California (1999-2001): emergence of Bartonella as a prevalent etiologic agent, J Vet Intern Med 18:56, 2004. Pappalardo BL et al: Immunopathology of Bartonella ­vinsonii (berkhoffii) in experimentally infected dogs, Vet Immunol Immunopathol 83:125, 2001. Pesavento PA et al: Pathology of Bartonella endocarditis in six dogs, Vet Pathol 42:370, 2005. Raoult D et al: Outcome and treatment of Bartonella endocarditis, Arch Intern Med 163:226, 2003. Reynolds HR et al: Sensitivity of transthoracic versus transesophageal echocardiography for the detection of native valve vegetations in the modern era, J Am Soc Echocardiogr 16:67, 2003. Rolain JM et al: Bactericidal effect of antibiotics on Bartonella and Brucella spp.: clinical implications, J Anti Chemother 46:811, 2000. Sisson D, Thomas WP: Endocarditis of the aortic valve in the dog, J Am Vet Med Assoc 184:577, 1984. Zeaiter Z et al: Diagnosis of Bartonella endocarditis by a real-time nested PCR assay using serum, J Clin Microbiol 41:919, 2003.

C hapter 

174

Dilated Cardiomyopathy in Dogs Daniel F. Hogan, West Lafayette, Indiana Henry W. Green, III, West Lafayette, Indiana

D

ilated cardiomyopathy (DCM) is an idiopathic myocardial disease characterized by systolic and diastolic dysfunction with chamber dilation ­primarily involving the left ventricle and variable right ventricular changes. This disorder represents one of the most common acquired cardiac diseases in dogs (13.6%), with only degenerative valve disease (47.8%) and in some regions heartworm disease more prevalent. Typically DCM results in clinically important morbidity and mortality, including congestive heart failure (CHF) and sudden death, which is often secondary to ventricular arrhythmias. The latter appears to be breed related with the highest incidence within the Doberman pinscher and boxer breeds (Sisson, O’Grady, and Calvert, 1999) (see Chapters 175 and 176). This chapter considers the etiology, diagnosis, and chronic therapy of dogs with DCM. Chapter 171 provides additional recommendations for treatment of CHF, including hospital therapy.

Etiology Systolic dysfunction with resultant cardiac dilation is thought to be the final common outcome of a variety of myocardial insults, including cytosolic, metabolic, immunologic, genetic, and infective mechanisms. In canine DCM most of these potential insults remain to be studied; thus the term idiopathic is most appropriate. Sporadically recognized causes of canine DCM include viral ­myocarditis, incessant tachycardia, taurine depletion, and possibly ­carnitine deficiency. In cases in which specific causes can be identified, an appropriate modifier should be used to describe the ­etiology of the disorder (i.e., taurine-­deficiency ­cardiomyopathy). In humans familial inheritance of numerous genetic mutations, often those encoding cytoskeletal proteins, appear to be the most common basis for DCM and represent 20% to 50% of DCM patients (Wynne and Braunwald, 2001). The overrepresentation of certain breeds and familial inheritance patterns suggest a genetic cause for canine DCM as well. Recently the giant myofilament protein titin has gained ­considerable interest in Doberman pinchers (Meurs, 2005).

Clinical Diagnosis Although DCM generally is described as one disease, ­clinical signs and progression of the disease demonstrate some breed variation. Because of these differences, the specific breed should be considered when assessing an 792

individual animal with respect to etiology, therapeutic protocol, and prognosis.

Signalment and History Dilated cardiomyopathy is usually considered a disease of large- and giant-breed dogs, with males generally having a higher ­incidence. Certain breeds are overrepresented, and there is some geographic variation. North American surveys suggest increased prevalence in the Doberman pinscher, Irish wolfhound, Great Dane, boxer and American cocker spaniel; whereas European surveys identified an increased risk for the Airedale terrier, Newfoundland, Doberman pinscher, and English cocker spaniel (O’Grady and Sullivan, 2004). Other breeds that we commonly observe include Dalmatians, German shepherds, and standard poodles. With the exception of the Portuguese water dog, in which clinical signs are often manifested before 12 weeks of age, DCM is commonly regarded as an adult-onset genetic disorder. Because of the potential benefit from early intervention, evaluation for occult (asymptomatic) disease can be considered in the breeds listed here. Clinical signs in dogs with DCM may be absent (preclinical or occult disease) or so subtle that they are overlooked. Some historical signs that should raise suspicion include mild exercise intolerance and weight loss. However, most often DCM is not diagnosed until clinical signs of overt CHF (coughing, tachypnea, dyspnea, and ascites) are present. As mentioned previously, sudden death is sometimes the first clinical sign of DCM in previously asymptomatic dogs.

Physical Examination Although not present in every case, it is common for a soft (grade 1-3/6) systolic murmur to be heard over the mitral or tricuspid valve regions as a result of mitral or tricuspid valve insufficiency. Louder murmurs can be heard if there is concurrent degenerative valvular disease. A low-frequency early diastolic sound (S3 gallop) may be noted over the left apex, indicating ventricular dilation and elevated atrial pressure. Femoral arterial pulses are usually weak as a result of reduced stroke volume from decreased systolic function. Pulse deficits are the hallmark of an arrhythmia such as atrial fibrillation. Pulmonary auscultation may reveal crackles and increased bronchovesicular lung sounds secondary to pulmonary edema or muffled sounds if pleural effusion is present. Jugular venous distention, hepatomegaly, and ascites may be noted in dogs with biventricular CHF.



Electrocardiography Most dogs with systematic DCM exhibit changes consistent with left ventricular enlargement and possibly left atrial enlargement. Cardiac arrhythmias, including sinus tachycardia, atrial fibrillation, and ventricular arrhythmias, are commonly identified. Conduction disturbances, including partial or complete left bundle branch blocks, are seen occasionally. Ventricular premature complexes (VPCs) are common in Doberman pinschers and boxers with DCM and may require 24-hour ambulatory electrocardiographic (AECG) monitoring to fully characterize the rhythm disturbances. However, frequent VPCs may also be seen in boxers with what has been called arrhythmogenic right ventricular cardio­ myopathy (previously described as boxer cardiomyopathy) (see Chapter 175) or similar clinical variant without concurrent DCM. The presence of VPCs may be a marker for occult DCM. Several studies in Doberman pinschers have found a clinical association between the number and complexity of ventricular arrhythmias and the development of DCM. One study demonstrated that nearly all dogs with frequent VPCs on AECG (>50 to 100/24 hour) went on to develop overt DCM (Sisson, O’Grady, and Calvert, 1999). Atrial fibrillation appears to be more prominent in but not limited to giant-breed dogs such as Irish wolfhounds, Great Danes, and Newfoundlands. Two studies of giantbreed dogs revealed a 75% to 97% incidence of atrial fibrillation on initial presentation (O’Grady and Sullivan, 2004).

Thoracic Radiography Dogs with DCM usually exhibit moderate-to-severe generalized cardiomegaly. Because of conformational differences (deep thorax and upright heart), Doberman pinschers and boxers often have less impressive radiographic changes. Pulmonary venous distention and pulmonary edema are the hallmarks of left-sided CHF, whereas pleural effusion is often a sign of biventricular CHF.

Echocardiography Although a presumptive diagnosis of DCM can be made based on historical, physical examination, and ECG data, transthoracic echocardiography (TTE) allows a definitive diagnosis. Semiquantitative assessment of disease severity can also be determined. The hallmark of DCM from TTE is evidence of systolic dysfunction through alterations in multiple systolic indices, including reductions in percent fractional shortening, ejection fraction, and left ventricular area shortening along with increases in the E-point-to-­septal separation and end-systolic diameter indexed to weight (Sisson, O’Grady, and Calvert, 1999). There is dilation of the left ventricle and left atrium (increased diameter indexed to weight). The thickness of the interventricular septum and left ventricular free wall are normal to decreased. The right ventricle and right atrium are variably affected and may appear normal to severely dilated. Mitral valve leaflet excursions typically are diminished because of low cardiac output and decreased venous return. Color Doppler often ­documents a central jet of mitral regurgitation derived from mitral annular and ­papillary muscle distortion, although

Chapter  174  Dilated Cardiomyopathy in Dogs

793

this may be prominent if there is concurrent degenerative mitral valve disease. Diagnosis of affected dogs in the occult stage is far more difficult and controversial. In Doberman pinschers, in which occult disease has been studied most extensively, dilation of the left ventricle tends to precede systolic dysfunction; this may not be true for other breeds. Newer echocardiographic modalities may prove useful in the future to allow earlier detection of disease and potentially affirm equivocal results from TTE. One such modality is tissue Doppler imaging with determination of myocardial velocity gradient and mitral annular systolic motion velocity (Sm). Others include myocardial strain and left ventricular torsion. With further ­experience these novel techniques may be considered useful inclusions in any screening program for detection of occult DCM. Additional echocardiographic data that may differentiate ­equivocal cases include systolic time intervals, diastolic ­performance indices, and stress echocardiography.

Prognosis Generally DCM carries a guarded-to-poor prognosis, although this is influenced by factors such as etiology and stage of disease at the time of diagnosis. For example, DCM in some American cocker spaniels has been associated with taurine deficiency, in which supplementation (see section on Therapeutic Considerations) can result in improved function and prognosis. The prognosis for English cocker spaniels treated with conventional drugs only can be surprisingly long, often more than 2 years. Occult disease in Doberman pinschers can last from 2 to 4 years before overt disease develops, but it is not known if this holds true for other breeds. Once overt CHF is present, the prognosis is highly variable. In our experience most naive dogs (no treatment) with DCM that present in CHF and respond to initial therapy survive for at least 6 to 12 months, with some surviving 12 to 24 months and only a minority longer than 24 months. However, age at onset of CHF (younger is worse), breed, concurrent presence of dyspnea and ascites, and the presence of atrial fibrillation all appear to be negative prognostic indicators, as would be logical by the severity of the clinical signs (O’Grady and Sullivan, 2004).

Therapeutic Considerations There are many different views regarding the best ­therapeutic protocol for DCM and very few studies of high-grade evidence. It would seem reasonable, at least as a starting point, to parallel the commonly used ­tripletherapy protocol (diuretic, angiotensin-­converting enzyme (ACE) inhibitor, and positive inotrope) from the human literature; and there are published data to ­support the use of furosemide, ACE inhibitors, and pimobendan in dogs.

Diuretics Most dogs with DCM present in CHF; thus diuretics play a large role in initial treatment and long-term control of fluid retention. However, if CHF is absent at the time of

794

Section  VIII  Cardiovascular Diseases

presentation, diuretics are not used because they result in further activation of detrimental neurohormonal responses. In addition, because of the unregulated activation of these responses, diuretics should never be used as sole therapy. Furosemide Furosemide is the most commonly used diuretic and has a rather large dosage range (2 to 4 mg/kg q24-8h orally [PO]). It is prudent to use the lowest possible dose to avoid adverse effects such as dehydration and hypokalemia. The concurrent use of ACE inhibitors and positive inotropes allows less dependence on diuretics. Therefore a lower required dosage of furosemide, often in the range of 0.5 to 2 mg/kg/day divided BID or TID, can be effective in some dogs. Another reason for using the lowest possible dose of furosemide is that, if excessive diuresis occurs while receiving ACE inhibitors, an acute reduction in ­glomerular ­filtration rate (GFR) can lead to acute renal failure. Thiazides With chronic refractory CHF the dosage of furosemide can be increased progressively, or another diuretic may be added. The thiazides (hydrochlorothiazide, 2.2 to 4.4 mg/ kg q12h PO; chlorothiazide, 20 to 40 mg/kg q12h PO) are commonly chosen in this setting. The enhanced diuresis from their addition can be quite dramatic and, in fact, may be too great and result in dehydration, acute renal failure, and severe electrolyte derangements. We have found that the addition of these agents in a modified pulse therapy protocol (q12h given every third day) allows enhanced diuresis without inducing dehydration or hypokalemia. As the cardiac disease progresses, administration can be increased to every other day and then every day. Spironolactone Spironolactone, an aldosterone antagonist that has been classified as a potassium-sparing diuretic, can also be added to furosemide. Recent experimental data in dogs suggest that standard doses (2.2 to 4.4 mg/kg q12h PO) do not result in an appreciable diuresis in healthy dogs. The situation in CHF is less certain. Historically spironolactone has been used to help prevent hypokalemia induced by chronic diuretic therapy in the pre-ACE inhibitor era. With the advent of ACE inhibitor therapy, there was ­concern that concurrent use of spironolactone with ACE inhibitors might result in hyperkalemia from excessive

depression of aldosterone action and levels, respectively. However, clinically this is not commonly recognized and might be the result of the well-recognized phenomenon of aldosterone escape with ACE inhibitor therapy. Routine monitoring of potassium levels in dogs receiving concurrent spironolactone and ACE inhibitors is prudent, and ­excessive potassium intake should be avoided.

Angiotensin-Converting Enzyme Inhibitors The development of ACE inhibitors has made perhaps the greatest impact on medical management of DCM over the past 50 years. These agents prevent the formation of angiotensin II, which induces vasoconstriction, fluid retention, myocardial and vascular smooth muscle hypertrophy/fibrosis, aldosterone release, and enhancement of sympathetic nervous system activity. There are numerous drugs within the ACE inhibitor class; and, although there are some unique differences among the individual drugs, beneficial effects are seen across the class when used in dogs with DCM. These benefits include reduced signs of CHF and improved survival. Enalapril and benazepril are probably the best studied in dogs, but this is changing rapidly as additional drugs within this class become approved for use in dogs in Europe (Table 174-1). Unlike in mitral insufficiency, there appears to be a therapeutic role for ACE inhibitors in dogs with DCM of all stages because the renin-angiotensin-aldosterone system is activated early in the course of DCM, even before development of CHF. Many of these agents are labeled for use once or twice a day, but we generally use enalapril at a dosage of 0.5 mg/kg every 12 hours orally, especially with CHF. Some clinicians initiate therapy at 0.25 mg/kg every 12 hours orally and increase the dosage after followup renal function tests. Potential adverse effects for drugs of this class include gastrointestinal (inappetence, vomiting), renal (acute renal insufficiency), and hypotension. However, in our experience it is very uncommon for dogs to experience clinically evident hypotension. This may be because of a species difference in sensitivity to these drugs. The greatest risk appears to be a reduction in GFR usually associated with volume depletion, possibly from aggressive diuretic use. Therefore routine monitoring of renal parameters is recommended in dogs receiving ACE inhibitors. This is commonly done in practice by measuring renal values before drug therapy, 3 to 5 days after starting therapy or increasing dose or dosing frequency

Table  174-1 List of Commonly Used Angiotensin-Converting Enzyme Inhibitors in Dogs and Cats Generic Name

Trade Name

Dose (Dog)

Dose (Cat)

Benazepril Enalapril Imidapril Lisinopril Ramipril

Fortekor, Lotensin Enacard, Vasotec Prilium Prinivil, Zestril Altace

0.25-0.5 mg/kg q24-12h 0.25-0.5 mg/kg q24-12h 0.25 mg/kg q24h 0.25-0.5 mg/kg q24-12h 0.5 mg/kg q24-12h

0.25-0.5 mg/kg q24-12h 0.25-0.5 mg/kg q24-12h 0.25-0.5 mg/kg q24h 0.5 mg/kg q24h

of the ACE inhibitor or diuretic, and every 3 to 6 months while on chronic stable therapy. Renal values should also be measured any time a dog exhibits clinical signs such as vomiting, inappetence, or reduced urination. The concurrent use of nonsteroidal antiinflammatory drugs may increase the risk of renal insufficiency and reduce the clinical efficacy of these drugs. Two drugs within this class that should be highlighted because of their unique pharmacokinetic properties are lisinopril and benazepril. Lisinopril, unlike the remainder of the ACE inhibitors, is not a prodrug. Therefore it does not require metabolism to the active metabolite and can be used in dogs with concurrent hepatic insufficiency. Benazepril is excreted through both renal and hepatic routes and therefore does not appear to require altered dosing in dogs with mild-to-moderate concurrent renal insufficiency. The therapeutic advantage of these characteristics requires further study.

Positive Inotropes Increasing the strength of ventricular contractions in dogs with ventricular systolic dysfunction is naturally intuitive. However, only a few oral drugs confer a positive inotropic effect. These drugs as a class are associated with increased frequency of ventricular arrhythmias, especially in humans. The arrhythmogenic potential of inotropic drugs in dogs requires more study. Digitalis Glycosides Until recently digoxin was the only positive inotrope available orally in many countries, including the United States. Digoxin not only exhibits a weak inotropic effect but has the additional benefit of neurohormonal modulation. This results from a normalization of baroreceptor function, which leads to reduction in sympathetic and enhancement of parasympathetic nervous system activity. Although there has been no prospective study in veterinary medicine to evaluate the clinical efficacy of digoxin in DCM, there are anecdotal reports of increased quality of life. A large clinical trial in humans demonstrated reduced cardiovascular mortality, an overall significant reduction in hospital visits, and an improvement of quality of life. In addition, lower blood levels of digoxin have been shown to confer measurable benefits while reducing the risk for toxicity. There is a trend among veterinary cardiologists to achieve digoxin levels that are lower than those previously accepted as therapeutic in dogs (approximately 1 to 2 ng/ml). We prefer to use a dosing protocol of 0.003 to 0.005 mg/kg every 12 hours orally; the lower end is used for medium and large dogs or in dogs with concurrent renal insufficiency since digoxin is cleared primarily by the kidney. In very large dogs we often use 0.22 mg/m2 every 12 hours orally, but the initial dose should never exceed 0.25 mg every 12 hours. Digoxin levels are required to monitor therapy so appropriate up-or-down dose titrations can be made. In our practice digoxin levels are usually measured 6 to 8 hours after dosing, 7 to 10 days after initiating or changing the dose, whenever renal insufficiency is recognized or clinical signs of toxicity are present ­(inappetence, ­vomiting, diarrhea, arrhythmias), or every 6 months with stable chronic therapy. Some cardi-

Chapter  174  Dilated Cardiomyopathy in Dogs

795

ologists prefer to sample a trough 10 to 12 hours after the previous dose; however, this timing can be more difficult to achieve in the outpatient clinic. If toxicity is suspected, therapy should be discontinued until the digoxin level is known. For uncomplicated cases we consider levels from 0.7 to 1.5 ng/ml to be therapeutic. If toxicity is suspected within this range, we consider cutting the dose in half to see if signs abate. If clinical signs persist, we consider concurrent medication, or clinical disease. Higher serum levels (1.5 to 2.5 ng/ml) may be required to help manage atrial fibrillation with attendant risk of adverse effects. When atrial fibrillation with rapid ventricular response rate (>200 beats/min) is present, an oral loading protocol of 0.003 to 0.005 mg/kg every 8 hours orally for 48 hours can be used. This hastens the development of a therapeutic level. Pimobendan Pimobendan (Vetmedin) is a positive inotropic drug recently approved for use in dogs. The positive inotropic effect is caused by an increased sensitivity of troponin C for calcium and also by phosphodiesterase III inhibition. The latter mechanism also results in venous and arterial vasodilation, which is the reason this drug is referred to as an “inodilator.” Pimobendan also exhibits beneficial neurohormonal effects, which include a reduction in plasma norepinephrine levels and inflammatory cytokines such as tumor necrosis factor (TNF)-α and interleukin (IL)-1β. Adverse effects could include an increase in sinus rate and enhanced arteriovenous nodal conduction. Whether or not pimobendan is proarrhythmic requires more study. Clinical studies in dogs have revealed improved survival and improved quality of life and functional class of heart failure (Luis Fuentes, 2004). The standard dosing protocol is 025 to 0.3 mg/kg every 12 hours orally.

Antiarrhythmic Therapy Supraventricular Arrhythmias Cardiac arrhythmias are commonly encountered with DCM, with atrial fibrillation most frequently requiring clinical management. The focus of atrial fibrillation treatment is management of the ventricular response rate in most cases. However, pharmacologic and electrocardioversion techniques have been used successfully in some dogs (see Chapter 164). Pharmacologic management of atrial fibrillation is centered on slowing atrioventricular (AV) nodal conduction velocity through the use of digoxin, calcium channel blockers, and β-blockers. Digoxin is usually the first-line drug but is often ineffective by itself. For this reason diltiazem (0.5 to 1.5 mg/kg q8h PO) or atenolol (0.5 to 1 mg/kg q24–12h PO) is commonly added to the protocol. The β-blockers are hampered by the risk of decompensation at the doses commonly required to effectively control the ventricular response rate. For this reason we most commonly add diltiazem to digoxin and find this combination very effective. The use of cardioprotective β-blocker therapy for CHF will be discussed separately.

796

Section  VIII Cardiovascular Diseases

Ventricular Arrhythmias Certain breeds have a higher incidence of ventricular arrhythmias, including boxers and Doberman pinschers (see Chapters 175 and 176). The class III agents (sotalol, amiodarone) appear particularly effective at abolishing these arrhythmias. However, sotalol (1 to 2 mg/kg q12h PO) does have β-blocking properties and should be used very cautiously in these patients to avoid cardiac decompensation, although this is not a complete contraindication. Amiodarone (10 mg/kg q24–12h PO for 7 to 10 days and then 5 to 10 mg/kg q24h PO) can be a very effective antiarrhythmic drug with less negative inotropy then sotalol. However, amiodarone can be associated with adverse effects, including hepatotoxicity and altered thyroid function. The class Ib drug, mexiletine (4 to 10 mg/kg q8h orally) also appears to be quite effective. Efficacy may be enhanced with ­concurrent use of atenolol, sotalol, or another β-blocker.

Ancillary Treatments Nutritional Therapy Amino acid supplementation.  There is growing evidence that amino acid deficiencies may be more common in dogs with DCM than previously suspected, but these cases still comprise a small minority of the DCM population (Bonagura, 2000). The prevalence of carnitine deficiency with DCM does not appear large, and many dogs do not demonstrate a clinical response to supplementation alone. An accurate diagnosis usually requires an endomyocardial biopsy because serum levels are often normal or even elevated with myocardial deficiency. Carnitine supplementation (50 to100 mg/kg q12–8h PO) is relatively expensive but may be helpful in some dogs. Taurine deficiency has also been recognized, especially in some specific breeds such as the American cocker spaniel, golden retrievers, and Newfoundlands and in dogs eating custom and lamb-rice diets. Unlike carnitine, an accurate assessment of taurine status can be determined by measuring serum or whole blood levels, and supplementation has been associated with a positive clinical response. Taurine levels should be measured when DCM is recognized in a dog from one of the previously mentioned breeds, in a breed uncommonly diagnosed with DCM, or in a dog receiving an unusual or unbalanced diet. Taurine supplementation (500 mg q12h PO) should be given to dogs with a documented deficiency or while levels are pending in dogs suspected as being deficient. Taurine supplementation is not expensive; thus a 3- to 6-month therapeutic trial in lieu of a documented deficiency could be considered. Reduced sodium intake.  Reduced dietary intake of sodium helps prevent excessive fluid retention and less dependence on diuretics. Modest-to-moderate sodium restriction is prudent, but excessive restriction results in reduced diet palatability and possibly activation of neurohormonal systems. We have found the following diets helpful: Purina (CV, NF) and Hill’s (k/d, g/d, and h/d). However, this list should not be considered exhaustive. See Chapter 157 for more details about diet and supplementation. Antioxidants There is some evidence that antioxidants may play a beneficial role in cardiovascular disease through ­reduction in

inflammatory cytokines (i.e., TNF-α and IL-1β). Supple­ mentation with omega-3 fatty acid products (780 mg of eicosapentaenoic acid [EPA] and 497 mg of docosahexa­ enoic acid [DAA] per day) is safe, inexpensive, and has been shown to exhibit beneficial effects (Smith, 2007). b-Blockers.  Chronic activation of the sympathetic nervous system can result in myocardial remodeling, fibrosis, and reduced function. Clinical data from humans suggest that chronic β-blocker therapy results in improved cardiac function and survival. Although data are absent in veterinary medicine, it is possible that dogs with DCM may also benefit from these agents. However, these agents can cause decompensation if the dose is too high or the animal particularly sensitive to sympathetic withdrawal. For these reasons these drugs should only be used in dogs with occult or compensated disease, or treated DCM and at very low initiating doses. The two drugs that have received the most attention in veterinary medicine are metoprolol and carvedilol. Both of these drugs provide nonspecific β-blockade; but carvedilol also exhibits potent antioxidant properties and α–blockade, although this last effect seems to be weak and may not exert a clinical impact. Both of these agents appear to be relatively safe in dogs when used in a slow up-titration dosing regimen (metoprolol, 0.1 mg/kg q12–8h PO; carvedilol, 0.04 to 0.1 mg/kg q12h PO) when the dose is increased every 7 to 14 days to a maximum tolerated dose or 1 mg/kg for either drug (Abbott, 2004). Spironolactone.  Spironolactone may exhibit a weak diuretic effect at best in the dog, but it may hold greater promise as an antimitogenic agent by interfering with the remodeling and fibrotic effects of aldosterone. In a large human clinical trial it was found that the addition of a once-a-day, subdiuretic dose of spironolactone to standard cardiac therapy resulted in a reduction in overall mortality by more than 30%. Although there are no clinical data in veterinary medicine to support a similar effect in dogs with DCM, it is now common to use spironolactone in this manner. There is no established once-a-day low dose for dogs, but we use an empiric regimen of 6.25 mg q24h orally for dogs less than 10 kg, 12.5 mg q24h orally for dogs 10 to 25 kg, and 25 mg q24h orally for dogs more than 25 kg. Intermittent dobutamine infusion.  Dobutamine is a very effective drug for treatment of cardiogenic shock in dogs with DCM (see Chapter 171). It has been documented in the human literature that some chronic refractory heart failure patients demonstrate a positive clinical response to intermittent dobutamine therapy. These beneficial effects are sometimes seen for a period of time longer than the infusion period. We have used this protocol occasionally; dobutamine is infused at 5 to10 mcg/kg/ min intravenously for a 12- to 24-hour period. It is difficult to say whether this therapy is effective, but some dogs seem to have had a positive clinical response.

References and Suggested Reading Abbott JA: Beta-blockade in the management of systolic dysfunction, Vet Clin Small Anim 34:1157, 2004. Bonagura JD, editor: Kirk’s current veterinary therapy XIII (small animal practice), Philadelphia, 2000, Saunders, p 761. Fuentes VL: Use of pimobendan in the management of heart failure, Vet Clin North AM (small Anim Pract) 34:1145, 2004.



Chapter  175  Cardiomyopathy in Boxer Dogs

Meurs KM: Primary myocardial diseases in the dog. In Ettinger SJ, Feldman EC, editors: Textbook of veterinary internal medicine, ed 6, St Louis, 2005, Elsevier, p 1077. O’Grady MR, O’Sullivan ML: Dilated cardiomyopathy: an update, Vet Clin Small Anim 34:1187, 2004. Sisson DD, Kittleson MD: Management of heart failure: principles of treatment, therapeutic strategies, and pharmacology. In Fox PR, Sisson DD, Moïse NS, editors: Textbook of canine and feline cardiology: principles and clinical practice, ed 2, Philadelphia, 1999, Saunders, p 216. Sisson DD, O’Grady MR, Calvert CA: Myocardial diseases of dogs. In Fox PR, Sisson DD, Moïse NS, editors: Textbook of

canine and feline cardiology: principles and clinical practice, ed 2, Philadelphia, 1999, Saunders, p 581. Smith CE et al: Omega-3 fatty acids in boxer dogs with arrhythmogenic right ventricular cardiomyopathy, J Vet Intern Med 21:265, 2007. Wynne J, Braunwald E: The cardiomyopathies and myocarditides. In: Braunwald E, Zipes DP, Libby P, editors: Heart disease: a textbook of cardiovascular medicine, ed 6, Philadelphia, 2001, Saunders, p 1751.

C hapter 

797

175

Cardiomyopathy in Boxer Dogs Kathryn M. Meurs, Pullman, Washington Alan W. Spier, Tampa, Florida

B

oxer cardiomyopathy is a primary myocardial disease that typically presents in one of three forms: an asymptomatic form with ventricular premature complexes (VPCs); a symptomatic form with VPCs; and a form with ventricular dilation, myocardial dysfunction, and ventricular and supraventricular tachyarrhythmias. Affected dogs may live for years with the disease and remain asymptomatic, may die of sudden death, or may gradually progress to congestive heart failure. This disease is most commonly referred to as arrhythmogenic right ventricular cardiomyopathy (ARVC). ARVC is an adultonset familial disease that appears to be inherited in an autosomal-dominant fashion. The frequency of disease, as well as disease severity, increases with age. A small percentage of boxers with myocardial disease present for the first time with ventricular dilation and myocardial dysfunction without a history of ARVC. It is possible that these boxers have a separate myocardial disease with an etiology that might include an inherited carnitine deficiency, viral myocarditis, or some other myocardial insult that results in the development of a cardiomyopathic state.

Diagnosis Arrhythmogenic Right Ventricular Cardiomyopathy A single diagnostic test for boxer ARVC is unavailable, and the diagnosis is best based on the presence of a combination of findings that may include a family history of disease, the

presence of a ventricular tachyarrhythmia, a history of syncope or exercise intolerance, and the exclusion of other systemic and cardiovascular diseases that could be responsible for the clinical presentation. Generally a thorough physical examination, electrocardiogram, blood pressure measurement, and echocardiogram should be performed when a diagnosis is suspected. In addition, a Holter monitor provides important information for both the initial treatment and long-term management of the case and should be ­performed whenever possible. Physical examination findings may include the ­auscultation of a tachyarrhythmia, although it should be emphasized that many affected dogs have very intermittent bouts of the arrhythmia and the absence of a tachyarrhythmia during examination does not rule out the diagnosis. In addition, since this is primarily an electrical disease, the majority of affected boxers do not have a heart murmur, although a left apical systolic murmur of mitral regurgitation may be identified in the cases that also have myocardial dysfunction and many boxers have a left basilar ejection murmur of uncertain etiology. The classic electrocardiographic findings of ARVC include the presence of an upright VPC (left bundle branch block morphology) on a lead II electrocardiogram (Harpster, 1991). However, some affected dogs have a different morphology to their VPCs; or, since the arrhythmia is so intermittent, the electrocardiogram may not demonstrate any VPCs at all. It is important to note that a normal electrocardiogram does not exclude a diagnosis of ARVC; if suspicion exists because of clinical signs ­(syncope, ­exercise

798

Section  VIII  Cardiovascular Diseases

intolerance), auscultation of an arrhythmia, or a family history of disease, a 24-hour Holter monitor is strongly suggested. Even if occasional VPCs are identified on an in-house electrocardiogram, we generally recommend a Holter monitor to help provide the best assessment of overall frequency and complexity of the arrhythmia. In addition, a pretreatment Holter provides useful information when attempting to determine the efficacy and the potential proarrhythmia of treatment once it has started. The results of the Holter monitor can be very useful in establishing a diagnosis of ARVC, particularly if the electrocardiogram is within normal limits. It is unusual for mature adult dogs to have ventricular ectopy. The median number of VPCs detected on the Holter reading from 600 mature asymptomatic boxers was 10 VPCs in 24 hours. Therefore the identification of frequent ventricular ectopy (>100 VPCs/24 hours) in an adult boxer is strongly suggestive of a diagnosis of ARVC, particularly if there is significant complexity (couplets, triplets, bigeminy, or ventricular tachycardia) to the arrhythmia. However, in some cases a diagnosis of ARVC in the boxer is greatly suspected based on the breed and presence of syncope, but the Holter monitor reading is not clearly abnormal. This may be because of the significant dayto-day variability of VPC number (up to 83%) in affected dogs. In highly suspect cases it may be worth performing a second Holter monitor or an event monitor if the dog is syncopal. A blood pressure measurement and echocardiogram are recommended in cases of suspect ARVC. Although in the majority of cases the blood pressure, cardiac chamber sizes, and systolic function are within normal limits, an echocardiogram can rule out other less common causes of ventricular ectopy (e.g., neoplasia). Blood pressure measurement may give insights into additional systemic ­diseases that are capable of causing syncope. In addition, the echocardiogram is necessary to identify the small ­percentage of dogs with ARVC that develop right and left ventricular enlargement and myocardial dysfunction.

Dilated Cardiomyopathy A small percentage of boxers have a clinical presentation consistent with dilated cardiomyopathy. Affected dogs may present with syncope or signs of left heart failure, including coughing; tachypnea; or biventricular failure, including coughing, tachypnea, and ascites. Thoracic radiographs may demonstrate left or biventricular enlargement, pulmonary edema, and pulmonary venous congestion. The echocardiogram may demonstrate left or biventricular enlargement with systolic dysfunction. The etiology of these cases is unknown. A small percentage of the cases may have progressed gradually from ARVC; however, other etiologies for myocardial dysfunction, including l-carnitine deficiency or myocarditis, should be considered.

Screening Given the inheritable nature of ARVC, there is significant interest by breeders and enthusiasts of the boxer breed

for the development of a screening program. However, at this time there is no single ideal screening test, and consideration should be given to multiple factors, including a family history of ARVC and repeated abnormal Holter monitor readings. Given the adult-onset nature, many perform the first Holter monitor at the age of 3 years and continue on an annual basis. Holter monitor results should be evaluated for both the number of VPCs and the complexity of arrhythmia (e.g., singles, couplets, triplets, ventricular tachycardia). However, there are still many unanswered questions about ARVC and the relationship of the ventricular arrhythmia to the development of clinical signs. Some affected dogs can have thousands of VPCs and never develop clinical signs; others demonstrate severe clinical signs with a fairly low number of VPCs. We have not found the number of VPCs or the complexity of the arrhythmia to be statistically different in symptomatic (syncopal) dogs compared to asymptomatic affected dogs. Therefore the factors that determine which dogs will eventually become clinical for the disease are not known, which leads to additional frustration in screening for this disease. Breeders should be strongly encouraged to screen for the disease but should be advised about the significant complexities of screening and counseled not to remove dogs completely from a breeding program because of a single abnormal Holter reading. Annual Holter monitoring is strongly recommended, and an emphasis should be placed on the results of multiple annual Holters in an asymptomatic animal. The results of 24-hour Holter monitoring from over 600 asymptomatic adult boxers identified a median number of VPCs of 10, with 25% and 75% confidence intervals of 2 and 110 VPCs per 24 hours, respectively. Based on this information we have developed the following ­initial system for screening asymptomatic dogs. 1. 0 to 50 single VPCs/24 hour: interpreted as within normal limits 2. 51 to 100 VPCs/24 hours: interpreted as indeterminate; suggest repeating in 6 to 12 months 3. 100 to 300 single VPCs/24 hours: interpreted as suspicious; consider keeping out of the breeding program for 1 year and repeating the Holter study 4. 100 to 300 VPCs/24 hours with increased complexity (frequent couplets, triplets, ventricular tachycardia) or 300 to 1000 single VPCs/24 hours: interpreted as likely affected 5. More than 1000 VPCs/24 hours: interpreted as affected, may consider treatment as discussed in the following paragraphs These criteria are based on the evaluation of single Holter monitors in mature boxers with no history of syncope. Additional studies to evaluate the long-term outcome of boxers with arrhythmias are currently being performed. This information has been provided as a possible starting point for making screening recommendations. Multiple criteria should be considered for each dog before making any strict recommendations, including family history, evidence of any ongoing systemic disease that could be associated with the development of the ventricular arrhythmia, and repeated Holter studies.



Chapter  175  Cardiomyopathy in Boxer Dogs

Treatment

mic effect or may be less effective in some individual boxers with ARVC. Therefore, if possible, patients should be managed by assessing both a pretreatment and posttreatment (2 to 3 weeks after starting treatment) Holter monitor evaluation. This can help determine the effect of treatment and confirm that the arrhythmia has not gotten worse. Significant day-to-day variability (up to an 83% change in daily VPC number) has been observed in affected boxers (Spier and Meurs, 2004). Therefore a therapeutic response is considered when at least an 80% reduction in VPC number and a reduction in the complexity of the arrhythmia are observed on the posttreatment Holter reading. In addition, an increase in symptoms after starting treatment or a greater than 80% increase in the number of daily VPCs may suggest a proarrhythmic effect.

In affected boxers antiarrhythmic therapy has been shown to decrease the number of VPCs, the complexity (grade) of the arrhythmia, and the presence of syncope (Meurs et al., 2002). However, the ability of antiarrhythmic ­therapy to decrease the risk of sudden death in affected dogs has never been proved or disproved. In addition, ventricular antiarrhythmics can demonstrate important proarrhythmic effects. Therefore the risks and benefits should always be assessed when considering treatment. In the asymptomatic dog we generally recommend therapy to decrease the number and complexity of the arrhythmias if there are at least 1000 VPCs/24 hours or if runs of ventricular tachycardia or evidence of the R-on-T phenomenon exist. It should be remembered that some ARVC dogs die of sudden death without ever having any documented episodes of syncope; thus the absence of a syncopal history does not imply a lack of risk. Ideally boxers with syncope and ventricular arrhythmias should be treated after a 24-hour Holter monitor is performed to quantify the pretreatment arrhythmia. If the syncope is frequent or ventricular tachycardia is observed, a Holter monitor evaluation may not be performed so that therapy can be started as soon as possible. However, in these cases the absence of a pretreatment monitor may make it difficult to fully assess the response to therapy. Therefore, whenever possible, a Holter monitor evaluation is performed first, and the owner is then advised to start therapy immediately after removing the Holter (before the results are available) if great concern exists. Two therapeutic protocols appear to be most effective at reducing the number of VPCs and the degree of complexity of the arrhythmia. The first is sotalol (1.5 to 2.5 mg/kg q12h orally [PO]); the second is a combination of mexiletine (5 to 6 mg/kg q8h PO) with a β-blocker (atenolol (0.5 mg/kg q12h PO) or sotalol (1.5 to 2 mg/kg q12h PO)). Sotalol as a monotherapy is generally chosen first because of the low level of side effects and ease of dosing twice a day. However, in some dogs sotalol is less effective. In these cases adding mexiletine or switching to mexiletine and atenolol may be useful. Mexiletine can cause a loss of appetite or mild gastrointestinal upset, but the addition of a β-blocker allows a lower dose of mexiletine to be used to help reduce this side effect. In addition, mexiletine should always be given with a meal. Despite their potential for beneficial antiarrhythmic effects, the medications listed here can have a proarrhyth-

799

New Advances in Therapy The use of implantable cardioverters-fibrillators has gained popularity in humans with ventricular tachyarrhythmias. A defibrillator was successfully placed in one boxer with ARVC, although some complications were observed that were associated with programming limitations of the device. The long-term benefits of this type of therapy in dogs with this myocardial disease have yet to be studied.

References and Suggested Reading Basso C et al: Arrhythmogenic right ventricular cardiomyopathy causing sudden death in boxer dogs: a new animal model of human disease, Circulation 109:1180, 2004. Harpster N: Boxer cardiomyopathy, Vet Clin North Am Small Anim Pract 21:989, 1991. Keene B: l-carnitine supplementation in the therapy of dilated cardiomyopathy, Vet Clin North Am Small Anim Pract 21:1005, 1991. Meurs KM et al: Familial ventricular arrhythmias in boxers, J Vet Intern Med 13:437, 1999. Meurs KM et al: Comparison of in-hospital versus 24-hour ambulatory electrocardiography for detection of ventricular premature complexes in mature boxers, J Am Vet Med Assoc 218:222, 2001. Meurs KM et al: Comparison of the effects of four antiarrhythmic treatments for familial ventricular arrhythmias in boxers, J Am Vet Med Assoc 221:522, 2002. Spier AW, Meurs KM: Spontaneous variability in the frequency of ventricular arrhythmias in boxers with arrhythmogenic ­cardiomyopathy, J Am Vet Med Assoc 224:538, 2004.

C hapter  

176

Cardiomyopathy in Doberman Pinschers Clay A. Calvert, Athens, Georgia Kathryn M. Meurs, Pullman, Washington

C

ardiomyopathy (CM) in Doberman pinschers (DPs) is a common, inherited, slowly progressive primary myocardial disease. Based on anecdotal reports, we believe that CM in this breed was present in the United States and Canada as far back as the mid1940s and the incidence of CM in DPs has reflected the breed population since that time. The hallmarks of CM in DPs are heart rhythm disturbances (mostly ventricular tachyarrhythmia, sudden death [SD], or end-stage ­congestive heart failure [CHF]). Affected DPs appear to progress through a long asymptomatic preclinical or occult phase (Fig. 176-1). Ventricular premature complexes (VPCs) are often the first markers for CM in this stage and are initially infrequent. Some DPs have slightly increased left ventricular internal dimensions for several years, even from early adulthood, before VPCs appear. Holter recording evaluation is usually needed for earliest detection of VPCs, and the echocardiogram parameters are usually within the “normal” ranges at that time. Typically within 1 year after ventricular ectopy is identified the echocardiogram findings become equivocally abnormal. Within 2 years the echocardiogram findings become unequivocally abnormal. As left ventricular dilation and contractility worsen, VPCs tend to worsen, and potentially lethal ventricular tachycardia (VT) develops in at least 50% of affected DPs. SD is often the first sign of CM and is the outcome in 30% to 50% of patients. It typically occurs between 6 and 8 years of age, is associated with at least moderate dilation and decreased contractility of the left ventricle, and often occurs about 1 year before overt CHF would be anticipated. Over 50% of all overtly healthy DPs over 10 years of age have numerous VPC and/or echocardiographic abnormalities. Many of these DPs die of comorbid ­disease, and CM is often not identified because cardiac workups have not been performed.

Etiology and Genetics The breeding history of the DP in North America is one of extreme inbreeding. Until recently virtually all DPs born in the United States and Canada could be traced to one of seven sires. “The seven sires” came from champion German stock imported into the northeastern United States and Canada during the late 1930s and early 1940s and were all closely related; the older three sired the younger four. Three of the seven died suddenly and unexpectedly in middle age. Many related DPs have been 800

exported throughout Europe since 1945, and many have been exported throughout the world in the past 30 years. In many cases the sires and/or dams of these dogs have subsequently died of CM. There is a distinct American flavor to the Dutch, English, and Australian DP. In addition, we have identified CM in numerous DPs imported to the United States from Europe. However, in general we believe that the incidence of CM in Europe is lower than in the United States and Canada. Although CM is known to be a familial disease, the genetics in DPs are not well understood. In humans approximately 25% to 30% of all cases are familial and can be autosomal dominant (about 50%), autosomal recessive, or X-linked. The mode of inheritance in DP was suggested to be autosomal dominant in one retrospective study. Mutations, usually single, each causing CM in humans, have been identified in most of the proteins of the sarcomere, cytoskeleton, and sarcolemma. If CM in DPs is an autosomal-dominant trait, it should appear with almost equal prevalence in both genders, and there should not be any silent carriers. All affected dogs should have at least one affected parent. However, in some cases it may appear as if neither parent was affected if the dogs died of noncardiac disease before the CM has developed. Although several studies have been performed to try to determine the molecular basis for the disease, and two genes (actin, desmin) have been eluded, the genetic ­etiology remains undefined.

Screening and Early Diagnosis We strongly recommend annual screening of adult DPs for preclinical CM. Without careful screening SD is often the first sign of CM, or CM is unrecognized until the endstage of CHF is reached. CHF carries a short and subsequent survival time of less than 1 to 6 months (mean 3 to 4 months) in most DPs treated with conventional drugs. Screening should include both echocardiography and Holter monitor evaluation beginning at 2 to 3 years of age. The likelihood of finding VPCs and echocardiographic markers for CM increases with age. The most important Holter recording markers for CM are VPCs that usually arise from the left ventricle. Twenty-four–hour Holter recordings containing more than 50 VPCs, any couplets or triplets of VPCs, or runs of VT indicate in our experience that the echocardiogram will be abnormal or equivocally progress to this stage within 1 year. Statistical analyses of large numbers of DPs

Chapter  176  Cardiomyopathy in Doberman Pinschers



Genetic defect

Typical time line (years of age)

No detectable abnormalities

2-5

VPC

3-6

VPC Plus Early echocardiographic abnormalities

4-7

Mean6-9 (Range, 3-12)

Mild to severe ventricular tachyarrhythmias Plus Moderate echocardiographic abnormalities

2-3 Years

Sudden adays to Syncope death (30%-50%) 6 weeks

Medians Male, 7-8 Female, 9-10 Range, 1-15

CHF Death (mean 3-4 months) CHF

Sudden (25%-30%)

Fig. 176-1  Typical evolution of cardiomyopathy in Doberman

pinschers. Arrhythmia and echocardiographic abnormalities can begin as early as 1 year of age or as late as at least 11 years of age. Disease evolution is accelerated when markers appear at a young age and is slower when markers first appear at old age. Syncopea due to ventricular tachycardia is a marker that survival to the end-stage of congestive heart failure is unlikely; rather sudden death intervenes in spite of therapy.

indicate that even one VPC correlates with increased risk of CM. However, for any one DP, on rare occasions fewer than 50 isolated VPCs may be ­considered “normal.” Any VPC detected during static electrocardiogram (ECG) in DPs is probably the result of CM unless another etiology can be identified. Arrhythmias can begin as young as 9 to 12 months of age and often begin around 2 to 4 years of age; by 6 years of age about 50% of all overtly healthy DPs have VPCs. In DPs with normal to equivocally abnormal echocardiograms the severity of arrhythmia is ­generally mild, total VPCs/24 hours vary from less than 100 to a few thousand, and life-threatening VT is generally absent. Rapid VT is common after the left ventricular end-­systolic dimension exceeds 40 mm, end-systolic dimension exceeds 50 mm, and the fractional shortening declines to less than 23%. Although arrhythmias very often begin when echocardiographic ­parameters are within the normal ranges, retrospective analyses of serial echocardiograms in these DPs indicate that these ­parameters progressively change from normal to abnormal. By 1 to 2 years after the onset of VPCs, echo parameters become ­unequivocally ­abnormal. Thus, unless screening is begun at 2 to 3 years of age, the odds are that, when the ­arrhythmias are first

801

detected, even by Holter recordings, the echocardiogram will be abnormal. The standard ECG is useful if VPCs are detected, and in most cases at least moderate dilation and systolic dysfunction of the left ventricle are present. Prolongation of the P wave and/or QRS complex duration often correlates with severe myocardial failure. Without treatment, SD or CHF is likely within 9 months. Low-voltage, wide R waves with a “sloppy” or slurred down-stroke of the R wave also suggest advanced myocardial failure and impending CHF. Compared to age, gender, and size, matched breeds of dogs that have a low incidence of CM, it is our experience that the heart of most normal DPs is not as ­muscular. Thus the normal echocardiographic parameters that we use are specific for the DP. The most useful M-mode echocardiographic markers of occult CM in order of importance are left ventricular end-systolic dimension, end-diastolic dimension, and fractional shortening. The distinction between a normal and equivocally abnormal echocardiogram is confounded by the limited accuracy of the test, interexaminer variability, and stress level (adrenaline) ­during the test. Generally overt signs of depressed left ventricular ­function in sedentary dogs are not evident until the left ventricular end-diastolic dimension and fractional shortening are greater than 55 mm and less than 20%, respectively. In active dogs the owners may recognize exercise intolerance in dogs with mild ventricular dysfunction but often attribute it to age. Mitral regurgitation (MR) is found by Doppler when the left ventricular end-systolic dimension is moderately increased. MR is often the result of dilation and decreased systolic contraction of the annulus or papillary muscles, but myxomatous mitral and tricuspid valve degeneration are also common in middle-aged and older DPs. MR is relatively severe in some DPs and confounds the differential diagnosis of “large-dog MR” versus CM. Moderateto-severe MR facilitates fractional shortening and worsens left atrial dilation. In these DPs left atrial dilation is disproportionately severe relative to reduced fractional shortening compared to DPs with mild CM and mild MR. However, standard ECG and Holter recordings from these DPs consistently demonstrate ventricular ectopy, and SD is sometimes the outcome.

Syncope Syncope in DP is usually caused by rapid, sustained VT. The likelihood of surviving an episode of rapid, sustained VT is probably related to the left ventricular ejection fraction. The lower the ejection fraction, the more likely VT will degenerate to fibrillation and cause SD. Aggressive antiarrhythmic treatment is indicated and usually retards SD, but our experience is that “syncopal” dogs nonetheless will die suddenly usually within 1 year. A less common cause of collapse in this breed is reflex-mediated (neurocardiogenic) syncope. This is an adrenergic­stimulated vagal reflex of bradycardia and vasodilation triggered by fight, flight, fright, or startle scenarios. In this breed neurocardiogenic bradycardia can be benign but is still a marker for CM and must be distinguished from­ VT-induced episodic weakness or syncope. The presence

802

Section  VIII  Cardiovascular Diseases

of numerous VPCs or VT contained in routine ECG or Holter recording indicates VT as the likely cause of syncope. The onset of atrial fibrillation can also precipitate episodic weakness and syncope.

Sudden Death Sudden death is the outcome in at least 30% of affected DPs, is as high as 50% in some lines, and exceeds 50% in some families. Syncope, presyncope, and SD are the result of sustained (greater than 30 seconds), rapid VT. If VT stops spontaneously, the patient quickly recovers; but SD is the outcome if the VT degenerates into ventricular fibrillation. Premonitory events of syncope may not precede SD; in other words, the first faint is the last one. Should spontaneous recovery occur and antiarrhythmic treatment not be initiated, another episode is likely within hours to weeks. Rarely does a DP survive three separate episodes. Left untreated, syncope or presyncope caused by VT usually is followed by SD within 1 or 2 weeks, and survival beyond 6 weeks is rare. Sudden death occurs more often in the morning and during or immediately following exertion-excitement, but it can occur during sleep. In our experience life-threatening ectopy does not occur until left ventricular systolic function is at least moderately depressed. Lethal VT is often associated with end-diastolic dimension greater than 50 mm, end-systolic dimension greater than 45 mm, and fractional shortening between 18% and 23%. Among the surviving subset, progression of left ventricular dysfunction is associated with a lower incidence of SD until the onset of CHF.

Treatment Guidelines There is no general agreement regarding treatment guidelines for occult CM. We recommend treatment for myocardial failure when the echocardiogram is unequivocally abnormal (i.e., when the left ventricular end-systolic dimension is greater than 40 mm, the end-diastolic dimension is greater than 50 mm, and the fractional shortening is less than 25%). Ideally treatment is based on all three parameters, but in selected DP it may be based on one or two measures because early myocardial failure is not always “textbook”. In addition, we usually do not initiate treatment until the E-point-to–septal separation is greater than 10 mm, a ­finding typical of ventricular dilation and myocardial failure. Based on studies in humans, three available classes of drugs may exert a favorable influence on progression of myocardial degeneration and systolic dysfunction: angiotensin-converting enzyme (ACE) inhibitors, aldosterone receptor antagonists, and β-adrenergic receptor blockers. There is little documentation on the influence of these drugs on disease progression in DPs with occult CM. We believe that therapy with an ACE inhibitor initiated before onset of CHF can significantly retard the progression of myocardial failure or CHF. Suggested dosage schedules include enalapril (Enacard, Merial; 0.25 mg/kg q12h orally [PO] for 1 week and then 0.5 mg/kg q12h orally) or benazepril (Lotensin, Novartis; 0.25 mg/kg q24h PO or q12h for 1 week and then 0.5 mg/kg q 24h PO or q12h PO). Also consider spironolactone (Aldactone, Searle; 1 to 2 mg/kg q 12h PO) in combination with the

ACE inhibitor at this stage. Spironolactone exerts potentially ­beneficial actions on the myocardium and vasculature. The ACE inhibitor–spironolactone combination increases potassium and magnesium serum concentrations, which may reduce arrhythmia. Spironolactone may exert an antifibrotic action (blocking cardiac fibroblast ­receptors) and may slow progressive myocardial fibrosis. β-Blockade has been shown in numerous human studies to exert a favorable influence on both SD risk and progression of myocardial degeneration. Clinical studies in DPs have not been reported. The addition of carvedilol to the treatment regimen 2 weeks after initiating ACE inhibitor treatment can be considered in DPs with occult CM. We use carvedilol (Coreg, SmithKline Beecham) at 12.5 mg every 12 hours orally for 1 week and then 25 mg every 12 hours orally because it may be the most effective β-blocker in humans with CM. Carvedilol is also a vasodilator (α-blockade) and a potent antioxidant, and it has anti-­endothelin activity. The drug is expensive currently. A dosage of 25 mg every 12 hours produces blood levels that are ­associated with mild-to-moderate β-blockade in DPs, depending on patient size. After 2 additional weeks an increase to 37.5 mg every 12 hours is recommended in patients greater than 35 kg. In spite of its α-blocking (afterload reducing) activity, carvedilol embarrasses contractility if myocardial failure is severe. It is critical that high doses of carvedilol not be initiated in DPs with overt or impending CHF. For example, DPs with overt CHF and sinus rhythm sometimes cannot tolerate a starting dosage of 3.125 mg every 12 hours, and those with CHF and atrial fibrillation may not tolerate even 1.56 mg every 12 hours. However, overt adverse affects are uncommon if the fractional shortening is greater than 18%. The dosage of carvedilol may need to be adjusted downward should severe CHF occur. These regimens are based on the pathophysiology of CM and the success of these medications in humans. Extrapolating data from human studies and applying it to dogs are often inappropriate. We have not observed an obviously favorable influence of carvedilol or spironolactone on disease progression. A large randomized ­prospective study is needed. At least 30% of DPs with CM eventually experience lifethreatening ventricular ectopy. Such an incidence would seem to dictate aggressive therapy. However, most antiarrhythmic drugs have proarrhythmia activity, some are negative inotropes, and sustained efficacy has not been proven. In addition, adverse effects, mostly gastrointestinal disturbances, are common. Although SD in DPs with occult CM can be retarded, it probably cannot be prevented. Criteria for initiating antiarrhythmic treatment are controversial. We initiate treatment for: 1. Rapid (>200 beats/min) VT (Lown class 4) 2. Syncope with subsequent documentation of many VPCs (presumed Lown class 4) 3. Couplets or triplets of VPCs (Lown class 3) with greater than approximately 6000 to 8000 VPCs/24 hours. A standard ECG and even a 24h Holter ECG are short samples-in-time. Frequent (at least every 3 months) Holter recordings should be performed in affected dogs when possible because of the dynamic and progressive



Chapter  176  Cardiomyopathy in Doberman Pinschers

nature of arrhythmias in many DPs. In the face of refractory rhythm disturbances, Holter recordings may need to be repeated at 1- to 4-week intervals until the rhythm is stabilized. Because of the high risk of SD, some veterinarians prefer to treat all affected DPs presenting with VPCs or VT. In therapy of ventricular ectopy we recommend mexiletine (Mexitil, Boehringer Ingelheim) at 5 to 6 mg/kg every 8 hours orally for maintenance treatment. Mexiletine frequently causes gastrointestinal upset, but this may be significantly reduced if each dose is given with a small amount of food. If the patient is not already being administered carvedilol, initiate it at this time (if CHF is neither present nor imminent) since the combination of a β-blocker and mexiletine is more effective (in the shortterm) than either alone. Rapid and remarkable improvement in VT severity is usual following the initiation of mexiletine. However, in spite of treatment at least 50% of the ventricular arrhythmias in DPs with occult CM become refractory within 3 to 9 months. Under these circumstances consider the addition of amiodarone (10 mg/kg q12h PO for 5 days and then 5 mg/kg q24h PO). Initial follow-up Holter recordings in DPs administered amiodarone sometimes document improvement in the severity of VT, but long-term efficacy has not been proven, and all of the DPs that we have treated with amiodarone have died suddenly. Whether amiodarone exerts a favorable, unfavorable, or neutral effect on time to SD has not been determined. Amiodarone is associated with numerous adverse effects in humans. Even in large DPs we have consistently encountered gastrointestinal disturbances and reversible hepatotoxicity at a maintenance dosage of 400 mg once daily. A maintenance dosage of 200 mg once daily ­sometimes causes hepatotoxicity. Baseline, 1 week, and then monthly serum chemistry profiles are required.

803

As myocardial failure worsens, a positive inotrope should be considered. Pimobendan (Vetmedin, Boehringer Ingelheim) administered at 0.3 mg/kg every 12 hours orally is a potent inodilator that exerts a significant positive inotropic action in DPs with advanced CM. We do not recommend pimobendan in dogs with fractional shortening values of 20% or greater. Of major concern is the protracted administration of a powerful positive inotrope in patients with myocardial disease. Past experiences with such drugs have been unfavorable in dogs and humans because of increased SD risk. We have encountered worsening of VT and SD in some DPs treated long term with pimobendan. However, to be determined is whether SD risk in DPs administered pimobendan is greater than in those not administered pimobendan. In one study of overt CHF, pimobendan was associated with prolonged survival in DPs with CM (Luis Fuentes et al., 2002). We do not recommend digoxin for the treatment of CM in DPs except in the face of atrial fibrillation or sustained or frequent paroxysmal atrial tachycardia. In addition, we do not recommend furosemide treatment until CHF is imminent. Furosemide is used when patients develop nocturnal dyspnea, a gallop heart rhythm, or distended pulmonary veins or based on echocardiographic measurements of high preload.

References and Suggested Reading Luis Fuentes V et al: A double-blind, randomized, ­placebo­controlled study of pimobendan in dogs with dilated ­cardiomyopathy, J Vet Intern Med 16:255, 2002. Meurs KM: Primary myocardial disease in the dog. In Ettinger SJ, Feldman EC, editors: Textbook of veterinary internal medicine, Philadelphia, 2005, Saunders, p 1077.

C hapter  

177

Myocarditis Karsten E. Schober, Columbus, Ohio

M

yocarditis is one of the most challenging diagnoses in small animal cardiology and may be even more difficult to manage. The entity is rarely recognized clinically, the prevalence unknown and probably underestimated, the pathophysiology poorly understood, and the clinical presentation and course variable. Furthermore there is no commonly accepted diagnostic gold standard, and all current specific treatments are controversial. Myocarditis is defined as an insidious inflammatory disorder of the myocardium characterized by leukocytic infiltration and nonischemic myocyte degeneration and necrosis (Feldman and McNamara, 2000). Because there is no consistently recognizable clinical syndrome or specific noninvasive diagnostic test, the clinical diagnosis of both acute and chronic myocarditis remains problematic and is often only presumptive. There are a variety of causes; infectious agents seem most relevant. Primary myocarditis is presumed to be caused by an acute viral infection or a postviral autoimmune response, neither of which are well studied in dogs or cats. Secondary myocarditis is inflammation caused by a specific pathogen, including bacteria, protozoa, fungi, drugs, chemicals, physical agents, and systemic inflammatory diseases. The causal link between active, viral myocarditis and the subsequent development of dilated cardiomyopathy (DCM) is documented in humans but much less appreciated and explored in small animals. This chapter briefly considers some of the current ideas regarding the manifestations, potential importance, and management of myocarditis in dogs and cats.

Pathophysiology Myocarditis has both infectious and noninfectious causes (Table 177-1). Cardiotropic viruses, including those with ribonucleic acid (RNA) and deoxyribonucleic acid cores, are the predominant pathogens that lead to myocardial inflammation in humans (Feldman and McNamara, 2000). Current speculation is that 10% to 30% of human myocarditis is virus associated. However, with the exception of canine parvovirus, the importance of viruses in the development of myocarditis is largely undetermined in dogs and cats. Current knowledge of the pathogenesis of viral ­myocarditis stems mostly from laboratory animal ­studies. A viral infection of the heart follows a standard ­progression. Most viral pathogens enter the body through the upper respiratory or gastrointestinal tracts. Genetic susceptibilities that alter the autoimmune response to viral infections may be important at this stage. The acute phase (days 0 through 3; viremic phase; fulminant ­myocarditis) is characterized by systemic viremia, virus 804

binding to myocyte coreceptors, virus invasion into cardiomyocytes, and virus replication causing myocytolysis. Macrophage activation leads to the production and release of proinflammatory cytokines, including tumor necrosis factor (TNF), interferon-γ, various interleukins, and inducible nitric oxide (iNO). The subacute phase (days 4 through 14; inflammatory phase; postviral or lymphocytic myocarditis) is characterized by clearance of the viruses by natural killer cells, cytokines, perforin, and neutralizing antibodies. Attracted by cytokine release, mononuclear cells such as cytotoxic T and B lymphocytes enter the myocardium and may cause extensive cellular damage. By the end of this stage the virus has already been cleared from the body, but the ongoing immune response mediates the myocardial damage and cell death. In the final or chronic phase (days 15 and beyond; healing phase; chronic myocarditis) there is evidence of myofiber dropout and replacement fibrosis. Most patients recover completely. However, in others viral persistence and host-pathogen interactions lead to chronic inflammation, repetitive cycles of myocardial injury and repair, apoptosis, coronary microvascular spasm, and autoimmune effects. These responses can result in continued myocardial injury and slow evolution to DCM and heart failure. This may occur even after many years, and some cases of idiopathic DCM in dogs and cats may represent unrecognized viral myocarditis. Slow-growing nonviral agents such as Trypanosoma cruzi may also cause chronic myocarditis with progressive DCM-like pathology after a prolonged latent period (Bonagura, 1995, p 850). Cardiotoxic drugs and drug hypersensitivity reactions have been associated with myocarditis. The severity of histopathologic lesions resulting from any of these agents varies with the severity of the insult and the nature and magnitude of the host-toxin interaction. Cardiac injury and myocarditis in critically ill patients is often severe but remains most commonly unrecognized. Potential mechanisms for myocarditis in such patients include excess NO and proinflammatory cytokine production, endotoxins, direct bacterial damage, and ischemia and reperfusion. Traumatic injury of the heart caused by nonpenetrating chest trauma (referred to as traumatic myocarditis) may be associated with myocardial contusion, intramyocardial bleeding, inflammation, and myocardial degeneration and necrosis. Myocardial dysfunction is a rare consequence and almost always reversible, and arrhythmias are usually benign. There is no evidence of long-term myocardial damage and dysfunction after traumatic myocarditis in dogs and cats (Bonagura, 1995, p. 846).

Chapter  177  Myocarditis



Table  177-1 Causes of Myocarditis in Dogs and Cats Infectious

Physical Immune-mediated

Toxic Other

Viral (parvovirus,* distemper virus,* herpesvirus, coronavirus, others) Bacterial* (various) Rickettsial (Rickettsia, Ehrlichia, Bartonella*) Spirochetal (Borrelia,* Leptospira*) Fungal (various) Algaelike (Prototheca) Protozoal (Trypanosoma,* Toxoplasma,* Neospora, Hepatozoon) Parasitic (Toxocara, Trichinella) Traumatic chest or body impact Hyperthermia Postinfectious Systemic disorders Drug hypersensitivity Drugs Toxins Idiopathic

*Most commonly described.

Pathology Inflammation may cause the myocardial pallor with occasional areas of minute hemorrhage. Microscopically there is distortion of muscle fibers caused by interstitial edema and fiber necrosis. The inflammatory infiltrate is usually lymphocytic. Morphometric quantification of the lesions is essential, with 14 leukocytes/mm2 being the cutoff to distinguish between the presence and absence of myocarditis in humans. Immunohistochemical staining for T lymphocytes may be needed to establish the diagnosis. Depending on the causative agent, there may be more specific histologic features. Healing is often associated with interstitial fibrosis. A viral origin of myocarditis can only be proved if viral particles such as inclusion bodies or the virus itself are detected within an altered myocardium. This has become possible through molecular analysis of necropsy and endomyocardial biopsy specimens using new techniques of viral gene amplification, including polymerase chain reaction (PCR) and in situ hybridization. The histologic diagnosis of myocarditis was clarified by the Dallas criteria (see the following section on Clinical Manifestations and Diagnosis), but these unfortunately did not include immunohistochemistry to demonstrate a T cell–mediated immune response. The clinicopathologic classification of primary myocarditis originally proposed by Braunwald and associates is based on the onset of illness, left ventricular function, endomyocardial biopsy (EMB) findings, and clinical and histologic outcomes and led to four classes of myocarditis: fulminant, subacute, chronic active, and chronic persistent. This classification has not yet gained wide acceptance in veterinary medicine.

Clinical Manifestations and Diagnosis Myocarditis can create diverse clinical features. The diagnosis of acute myocarditis is made largely by clinical

805

history and a high index of suspicion rather than a ­definitive diagnostic test. It may follow upper respiratory or gastrointestinal infection, surgery, or recent drug exposure. General constitutional symptoms, particularly fever, anorexia, soft cough, muscle pain, exercise intolerance, and diarrhea, are often reported. There is no specific clini­ cal sign on which to base the diagnosis. Classically the combination of an acute infective illness and myocardial abnormalities such as a sudden onset of unexplained ventricular arrhythmia, syncope, episodic weakness, acute congestive heart failure (CHF), anesthetic death, or sudden death may suggest the diagnosis. Thoracic auscultation may disclose evidence of an arrhythmia, a cardiac murmur, or abnormal lung sounds such as crackles. Electrocardiography may reveal a variety of findings, including persistent sinus tachycardia, ST segment, QT and T wave abnormalities, ventricular or supraventricular ectopy, and atrioventricular (AV) conduction disturbances, including complete AV block (Kaneshige et al., 2007). Although such electrocardiogram (ECG) findings are nonspecific, the ECG has the virtue of drawing attention to the heart and leading to echocardiographic and other investigations. Radiography may be unremarkable or reflect cardiomegaly, venous congestion, and pulmonary interstitial and alveolar densities suggestive of CHF or pulmonary infection. As with other noninvasive techniques, echo­ cardiography may be unremarkable or display nonspecific findings. Diffuse or focal nodular thickening and heterogeneous granular texture of the myocardium caused by cellular infiltrates and pericardial effusion have been observed in association with acute (or fulminant) myocarditis. Segmental or generalized ventricular wall motion abnormalities and hypokinesis have been reported in humans and cats with histologically proven myocarditis. However, such changes may be confused with abnormalities caused by myocardial ischemia or infarction. The most important aspect of echocardiography may be its ability to exclude other types of myocardial and valvular heart diseases. Laboratory tests, including the analysis of serum cardiac troponin (cTn) concentration, is a promising approach to specifically diagnose acute myocardial injury. Unfortunately blood cTn is not altered consistently in myocarditis, nor is it specific of myocardial inflammation. In addition, the window for diagnosis may be relatively brief. Nevertheless, elevation of serum cTn in association with a strong clinical suspicion may aid in the early presumptive diagnosis of acute myocarditis in which significant myocytolysis and myocardial necrosis may occur (Fig. 177-1). Experimental studies in mice (Smith et al., 1997) and clinical studies in humans (Lauer et al., 1997) with histology-proven myocarditis reported on the high sensitivity of cTn in the diagnosis of acute myocarditis and the close relationship between serum concentrations of cTn and the severity of myocardial inflammation. The value of cTn in the diagnosis of chronic myocarditis is limited. Serologic testing for known infectious causes (including toxoplasmosis, borreliosis, rickettsial diseases, bartonellosis, and Chagas’ disease) may identify the causative antigen and assist in further treatment plans. EMB continues to be the most definitive test and gold standard to confirm myocarditis in vivo in humans; but it

Section  VIII  Cardiovascular Diseases

806

400

420.4 395.0 168.0

for refractory cases. Interestingly, PCR of tracheal aspirate samples looking for viral RNA has correlated highly with EMB results in humans and seems to be an alternative to EMB in situations in which acute viral myocarditis is suspected.

114.0

Serum cardiac troponin I (ng/ml)

80.0 65.0

50

40

30

20

10

0

Fig. 177-1  Serum cardiac troponin I (cTnI) concentration

in 60 dogs with the clinical diagnosis of acute myocarditis. Diagnostic criteria were the sudden onset of unexplained ventricular or supraventricular ectopy, abnormal diffuse or focal thickening of the left ventricle with granular texture of the myocardium on two-dimensional echocardiography, left ventricular systolic dysfunction with no or only minor chamber dilation, or vegetative endocarditis associated with ventricular tachyarrhythmias. Dogs with known structural heart disease (congenital and acquired), recent trauma, a splenic mass, and gastric dilation-volvulus syndrome were excluded. Open circles represent dogs with acute myocarditis confirmed by histopathology. Zero cTnI refers to the lower limit of detection of the immunoassay used (0.1 ng/ml; OPUS Troponin I, Dade-Behring Diagnostics Inc.). (From the veterinary medical data base of the Department of Small Animal Medicine, University of Leipzig, Germany (unpublished data).)

is used infrequently in small animals because of its ­invasive nature, limited sampling access, small sample size, relevant interobserver variability in the histologic assessment of the sample, and relatively low diagnostic yield. The diagnosis depends on the presence of inflammatory infiltrates and myocyte degeneration or necrosis. To standardize the histologic diagnosis of myocarditis in human- (and animal)model EMB specimens, the Dallas criteria were introduced by Aretz and colleagues in 1987. Such criteria distinguish between active myocarditis (presence of lymphocytes and myocytolysis), borderline or ongoing myocarditis (lymphocytic infiltration and absence of myocytolysis), and negative findings (absent lymphocytic infiltrates and myocytolysis). Since EMB does not appear to be a reliable method for making the diagnosis of myocarditis, biopsy is usually reserved

Management Principles The treatment of myocarditis is controversial, and no generally applicable therapeutic regimen has been established. Supportive care directed toward alleviating clinical signs is the first line of therapy. Specific aims of management are to stabilize cardiac pump function and reduce the risk of progression to heart failure, manage arrhythmias, and identify and remove infectious or toxic agents. There is good evidence from animal work that exercise in the setting of acute myocarditis is detrimental and therefore should be restricted. If an infectious cause can be identified or is suspected, it should be treated aggressively with effective antimicrobials. In patients with symptoms of heart failure, medical therapy should focus on reduction of cardiac load, improvement of ventricular pump function, suppression of exaggerated neuroendocrine activation and arrhythmias, and long-term cardiac protection. Treatment options include diuretics, angiotensinconverting enzyme (ACE) inhibitors, positive inotropes, spironolactone, and β-adrenergic blocking agents once clinical stability has been achieved. There is evidence from murine models that commonly used drugs for the treatment of CHF may have additional beneficial and more specific effects in acute myocarditis. The following treatments might be useful based on extrapolation from models. ACE inhibitors have been shown to directly decrease the amount of myocardial inflammation. Cytokine activation secondary to the inflammatory process results in the stimulation of nitric oxide synthase and the production of excessive amounts of NO from injured myocytes. This effect may be blunted with the positive inotrope pimobendan (Vetmedin, Boehringer Ingelheim) (0.2 to 0.3 mg/kg orally [PO] q12h) and the calcium channel antagonist amlodipine (Norvasc, Pfizer). In contrast, digitalis may increase the myocardial production of proinflammatory cytokines, induce vascular spasm, worsen myocardial injury, induce arrhythmias, and increase mortality in viral myocarditis. Therefore digoxin should be avoided or only used with extreme caution. β-Blockade may decrease the extent of myocardial damage and improve survival, presumably by relief of coronary vasospasm. Propranolol, sotalol, and carvedilol are preferred because of their nonselectivity. Hemodynamically relevant arrhythmias occur frequently and necessitate antiarrhythmic treatment (see section on Arrhythmogenic Right Ventricular Cardiomyopathy later in the chapter). Arrhythmias are commonly labile in acute myocarditis; and both the type of arrhythmia and the underlying electrophysiologic mechanism may change quickly. In addition, effective doses of antiarrhythmics are difficult to predict in dogs and cats with acute myocarditis and are often substantially different from commonly recommended doses. Occasionally dogs and cats with myocarditis need temporary or permanent cardiac pacing for AV block to achieve hemodynamic ­stabilization and relief of clinical signs.

Chapter  177  Myocarditis

A variety of new therapies for myocarditis are a ­ vailable in humans, including antiviral agents and vaccines, immunosuppression, and modulation of the biologic response to inflammation. The specific question for patients with myocarditis is whether regimens designed to reduce or eliminate inflammation can provide clinical benefits compared to conventional heart failure therapy. A number of agents, including nonsteroidal antiinflammatory drugs, intravenous immunoglobulin, methylprednisolone, cyclosporine, azathioprine, antiviral drugs, and anti-TNF, have been used to treat acute myocarditis in humans and experimental animals. However, results of recent randomized, placebo-controlled human trials have failed to demonstrate beneficial effects of immunosuppression. Moreover, nonsteroidal antiinflammatory drugs may be detrimental because they may reduce viral clearance, attribute to an exaggerated cytotoxic response, induce coronary ­vascular spasm, and delay myocardial repair (and many are toxic to dogs and to cats) (Meune et al., 2003). The future development of effective treatment will depend on early diagnosis and detailed knowledge of the pathogenesis of ­myocarditis and ­subsequent immune response.

Feline Myocarditis and Cardiomyopathy The incidence of myocarditis in cats is largely unknown. However, there is some evidence that acute endomyocarditis (EMC) may be of particular importance in the cat. In a series of 461 cats with cardiomyopathy first published by Liu in 1977 and later summarized in his review of cardiomyopathy (Liu, 1985). about 6% were diagnosed with EMC. Affected cats were young, with a mean age of 2.6 years (range 2.5 months to 8 years). Most cats (85%) with acute myocarditis died suddenly. Some cats were dyspneic and depressed and had leukocytosis for 1 to 2 days before death. In another retrospective study considering 1472 feline necropsies performed over a 7-year period, Stalis, Bossbaly, and Van Winkle (1995) reported on 37 (2.5%) cases of EMC and 25 (1.7%) cases of left ventricular endocardial fibrosis. Four (0.3%) cats had histologic evidence of both diseases. Similar to Liu’s study, cats with EMC were young (mean age at death 3.4 years, range 6 months to 14 years). Interstitial pneumonia was found in 71% of cats with EMC. Based on such studies it seems that antecedent respiratory infections and stress are potential precursors of EMC in cats and that restrictive cardiomyopathy and left ventricular endocardial fibrosis represent one late sequel to EMC (Stalis et al., 1995). Therapy of EMC in cats is symptomatic, mainly for CHF.

Arrhythmogenic Right Ventricular Cardiomyopathy Arrhythmogenic right ventricular cardiomyopathy (ARVC), a newly described myocardial disease in cats (Fox et al., 2000), is also characterized by a high incidence of myocarditis ­reaching 83% of affected cats in a small case series. Of note, the histopathologic changes of ARVC were not confined to the right ventricle. Similar but generally less marked lesions of myocardial injury and repair were also observed in the ventricular septum or the left ventricular free wall of most animals. However, the possible pathogenic role of ­myocardial

807

inflammation as a potential injury mediator in ARVC is still undetermined. Conventional heart failure ­therapy with furosemide, enalapril, and nitroglycerin and antiarrhythmic treatment with atenolol, sotalol, or procainamide are recommended. In the near future the use of pimobendan for inotropic support of the failing heart may be an additional treatment option in cats with ARVC and heart failure.

Toxoplasmosis Toxoplasmosis is a common but largely underappreciated cause of myocarditis in cats. Two case series of Toxoplasma gondii–infected cats (Dubey et al., 1993, 1996) revealed myocarditis in 62.7% and 100% of the animals by histopathology. However, there is only one single published report on the antemortem diagnosis of toxoplasmosis in a cat (Simpson et al., 2004). Oral clindamycin (8 mg/kg q8h or 12 mg/kg q12h PO) is the treatment of choice to clear the infection. Transmissible myocarditis and diaphragmitis (TMD) has been described in cats in northern California. Clinical signs included transient fever, depression, lethargy, and lymphadenopathy (Pedersen et al., 1993). All cats had histologyproven acute myocarditis and diaphragmitis characterized by small pale foci within the myocardium, intramyocardial hemorrhage, myonecrosis, and mononuclear cell ­infiltrates. A causative organism could not be identified.

Myocarditis in the Dog As with cats, the incidence of myocarditis in the general canine population is unknown. However, very similar to cats, a retrospective necropsy study, including 4638 consecutive dogs seen in the pathology department over a 9-year period at a European Veterinary Teaching Hospital, reported on 70 (1.5%) dogs with the histopathologic diagnosis of myocarditis (Venzin et al., 1990). Dyspnea was the most often encountered clinical sign, and arrhythmias occurred frequently, but sudden cardiac death was rare (4.2%). Inflammatory lesions were found equally distributed between both ventricles. Myocarditis was judged as primary in 33% and secondary in 67% of dogs and was suppurative in 67% of cases. Canine distemper, toxoplasmosis, leptospirosis, and leishmaniosis were the most often determined causes of secondary myocarditis. Parvovirosis.  Parvovirus myocarditis was an extensive problem in young puppies in the late 1970s and early 1980s, when the virus first appeared. Sudden cardiac death or acute death secondary to pulmonary edema was common. Apparently some dogs survived the neonatal infection and developed a disease clinically indistinguishable from DCM. Histopathologic characteristics were myofiber loss, myocytolysis, and lymphocytic and plasmacytic infiltrates (Liu, 1985). Large, basophilic intranuclear inclusion bodies found in the myocardium of acutely infected puppies were pathognomonic findings. No cases of parvovirus-induced myocarditis have been identified in the canine literature since the early 1980s. Chagas’ disease.  Chagas’ disease is a leading cause of myocarditis and myocardial failure in humans and dogs in Latin America. It is a rare disease in North America and is caused by T. cruzi, a hemoflagellate protozoon parasite (see Bonagura, 1995, p 850).

808

Section  VIII  Cardiovascular Diseases

Lyme disease.  Lyme carditis is a rare cause of myocardial disease in dogs. It is caused by infection with the spirochete Borrelia burgdorferi. Classically AV block, including complete heart block, is seen; but ventricular arrhythmias and myocardial failure occasionally occur. If Lyme carditis is suspected, diagnosis can be confirmed by antibody titers. The efficacy of antibiotic therapy (intravenous penicillin G and tetracycline) in Lyme carditis associated with AV block is not established. Symptomatic dogs with AV block may require temporary or permanent cardiac pacing. Bartonellosis.  Severe multifocal myocarditis and valvular ­endocarditis secondary to Bartonella vinsonii ssp. berkhoffi infection has recently been described in dogs. Diagnosis was based on seroreactivity to B. vinsonii antigens as determined by immunofluorescent assay testing. Conventional blood cultures generally failed to result in bacterial growth. Treatment with enrofloxacin, doxycycline, and azithromycin should be attempted; however, complete ­elimination of the infection may be difficult to attain. Atrial myocarditis.  A particular form of cardiomyopathy that ­preferentially destroys the atrial myocardium has been observed in dogs, most commonly in English springer spaniels. Myocardial destruction is most likely the result of a myocarditis of unknown etiology. Atrial standstill, a nodal escape rhythm, and complete AV block are observed frequently. The atrial cardiomyopathy may be followed by ventricular myocardial failure. Treatment includes permanent cardiac pacing and symptomatic medical therapy, including furosemide, spironolactone, an ACE inhibitor, and pimobendan. Long-term prognosis is poor because CHF or sudden death occurs early. Arrhythmogenic right ventricular cardiomyopathy.  As in cats, ARVC is associated with myocarditis in almost two thirds of cases, frequently affecting both the right and left ventricles. Because myocarditis was conspicuously present in all ARVC dogs with sudden cardiac death in one study (Basso et al., 2004), it is assumed that myocardial inflammation may also play a role in arrhythmogenesis. Therapy with class III antiarrhythmics, preferentially

sotalol at 1.5 to 3.5 mg/kg every 12 hours orally, is the­ preferred treatment option. Alternatively the combination of mexiletine (4-6 mg/kg q8h PO) and sotalol or atenolol (12.5 mg/dog q12h PO) has been used (see Chapter 175). However, evidence is lacking that antiarrhythmic therapy prevents sudden cardiac death in dogs with ARVC. The minority of dogs with ARVC that develop CHF should be treated symptomatically.

References and Suggested Reading Aretz HT et al. Myocarditis: a histopathological classification, Am J Cardiovasc Pathol 1:3, 1987. Bonagura JD, editor: Kirk’s current veterinary therapy XII (small ­animal practice), Philadelphia, 1995, Saunders. Dubey JP, Carpenter JL: Histologically confirmed clinical toxoplasmosis in cats: 100 cases (1952-1990), JAVMA 1556:2003, 1993. Dubey JP, Mattix ME, Lipscomb TP: Lesions of neonatally induced toxoplasmosis in cats, Vet Path 33:290, 1996. Feldman AM, McNamara D: Myocarditis, N Engl J Med 343:1388, 2000. Kaneshige T et al: Complete atrioventricular block associated with lymphocytic myocarditis of the atrioventricular node in two young dogs, J Comp Pathol 137:146, 2007. Lauer B et al: Cardiac troponin T in patients with clinically ­suspected myocarditis, J Am Coll Cardiol 30:1354, 1997. Liu SK: Myocarditis and cardiomyopathy in the dog and cat, Heart Vessels 1(suppl):122, 1985. Meune C et al: Risks versus benefits of NSAIDs, including aspirin in myocarditis: a review of the evidence from animal studies, Drug Safety 26:975, 2003. Smith SC et al: Elevations of cardiac troponin I associated with myocarditis: experimental and clinical correlates, Circulation 95:163, 1997. Stalis H, Bossbaly MJ, Van Winkle TJ: Feline endomyocarditis and left ventricular endocardial fibrosis, Vet Pathol 32:122, 1995. Venzin I, Ossent P, Glardon O: Myocarditis in the dog: Retrospective study on clinical and pathologic findings in 70 cases, Kleintierpraxis 35:161, 1990.

C hapter  

178

Management of Feline Myocardial Disease Virginia Luis Fuentes, Hatfield, Hertfordshire, United Kingdom

Classification of Myocardial Disease Ever since the descriptions of cardiomyopathy in cats in the early 1970s, the management of feline myocardial disease has been complicated by problems in distinguishing the different forms of myocardial disease. Although echocardiography has become the standard for recognition and staging of cardiomyopathy (Table 178-1), often the situation is not straightforward. Using the WHO classification of human cardiomyopathies as a basis for feline myocardial disease, feline cardiomyopathies were originally categorized as hypertrophic, dilated, restrictive, or unclassified, with the subsequent addition of arrhythmogenic right ventricular cardiomyopathy. However, the exact classification of the disease in individual cats has continued to be challenging, particularly since end-stage disease can result in a phenotype that does not fit comfortably in any category except “unclassified.” The problems of a classification with anatomic, functional, and etiologic roots have recently been addressed in a scientific statement by the American Heart Association (Maron et al., 2006). Human cardiomyopathies are now divided into primary (in which the myocardial changes are the major abnormality such as hypertrophic cardiomyopathy) and secondary (in which a multiorgan systemic disease such as hyperthyroidism also affects the myocardium). Primary cardiomyopathies are divided into those with a genetic basis, those with an acquired etiology, or those with a combination of genetic and acquired factors (mixed). Hypertrophic cardiomyopathy (HCM) and arrhythmogenic cardiomyopathy are considered genetic in humans, whereas dilated cardiomyopathy (DCM) and restrictive cardiomyopathy (RCM) are classed as mixed. There is now firm evidence that HCM can be genetic in cats: two separate mutations in myosin-binding protein C have been documented in Maine coons and rag dolls with HCM. There is also evidence that DCM can be acquired in cats with taurine-deficient diets. Nevertheless, in the majority of feline cardiomyopathy cases, we can only guess at the etiology. Cats are also affected with secondary cardiomyopathies such as hyperthyroidism and systemic hypertension, which commonly affect myocardial function. To add to these difficulties in classification, cats may progress from one phenotype to another. Myocardial infarction can complicate HCM, RCM, or DCM, resulting in regional wall thinning and hypokinesis irrespective of the original left ventricular (LV) morphology.

An end-stage form of HCM has also been described in human and feline patients, characterized by LV hypertrophy with dilation and reduced systolic function. Even on a genetic level, some mutations can be characterized by a DCM or HCM phenotype; thus it is no surprise that some feline patients are difficult to classify. For those who manage cats with myocardial disease in practical settings, it may be more important to stage the disease in individual cats rather than agonize over the correct classification of the type of cardiomyopathy. Asymptomatic cats with myocardial disease require different management from those with congestive heart failure (CHF). Table 178-2 outlines the use of different therapies according to the stage and type of cardiomyopathy. Specific clinical problems include distinguishing asymptomatic cats with HCM from cats with functional murmurs and distinguishing cats with CHF caused by myocardial disease from those with other causes of respiratory distress.

Approach to The Asymptomatic Cat with a Murmur The prevalence of murmurs in the healthy cat population is high, and many of these murmurs are probably associated with HCM (Côté et al., 2004). However, the finding of a murmur is never an indication for empiric therapy for heart disease. Some cats have low-to-moderate intensity systolic murmurs associated with high cardiac output and adrenergic states associated with anemia, hyperthyroidism, or fever. Other causes of sympathetic activation (stress, drugs) can be associated with a systolic murmur in healthy cats, and the murmur sometimes seems related to a hyperdynamic contraction of the right or left ventricle. Other disorders that may be associated with heart murmurs include systemic hypertension, congenital heart defects, and idiopathic aortic dilation. A significant number of cats have no obvious anatomic or physiologic cause of a heart murmur (functional murmurs). A good clinical workup considers each of these diagnoses; but once hyperthyroidism and anemia (high cardiac output states) have been ruled out, further diagnostics are usually necessary. A normal cardiac silhouette on radiographs does not rule out cardiomyopathy, but it is a good indication that minimal structural changes are present (i.e., the murmur is functional, or LV hypertrophy is mild). The six-lead electrocardiogram (ECG) probably has relatively good specificity for heart disease, but the sensitivity seems too low since many cats with structural heart 809

810

Section  VIII  Cardiovascular Diseases

Table  178-1 Two-Dimensional and M-Mode Echocardiographic Characteristics of the Main Feline Cardiomyopathies

Normal

Hypertrophic Cardiomyopathy

Restrictive Cardiomyopathy

Dilated Cardiomyopathy

Arrhythmogenic Right Ventricular Cardiomyopathy

Left atrial diameter

LA:Ao > 1.6 LAx 10,000 >100,000

>1000 >1000 >10,000

100-1000 1000-10,000 10,000-99,000

100-1000 100-1000 1000-10,000

MIC for 40% to 50% of the dosing interval are efficacious. Cefpodoxime proxetil, a third-generation cephalosporin, is attractive for use because of its once-daily dosing schedule but should be reserved for infections more serious than superficial pyoderma. The antistaphylococcal penicillins (cloxacillin, dicloxacillin, and oxacillin) are excellent for first-choice therapy of pyoderma. However, because of their limited spectrum of activity, these drugs are not usually on stock in a veterinary clinic, but they can be prescribed easily from a human pharmacy. Because of poor oral bioavailability and rapid renal elimination, they

1227

must be dosed every 6 hours, making client compliance difficult. The macrolides and lincosamides are reasonable choices for first-time treatment of pyoderma, but recurrent infections are likely to be resistant. Erythromycin is associated with a high incidence of gastrointestinal upset in dogs. This can be avoided by using enteric-coated tablets, administering with food, prescribing antiemetics for the first 2 to 3 days of therapy, and initiating therapy with a lower dose. This treatment regimen is too complicated and inconvenient for most clients, and most clinicians prefer to use antimicrobials that do not routinely induce vomiting. Lincomycin has the same activity as erythromycin and does not cause gastrointestinal upset. Clindamycin is very active against Staphylococcus spp. and anaerobic bacteria. It distributes well into tissues and is active in purulent material. Trimethoprim or ormetoprim combined with a sulfonamide are effective in most cases of superficial pyoderma, but the risks of adverse effects such as keratoconjunctivitis sicca and polysystemic drug reactions limit their use. Mupirocin is a topical therapy for localized pyoderma. It has excellent activity against gram-positive cocci, is not absorbed systemically, and is chemically unrelated to other antimicrobials. It is well tolerated in cats for the treatment of feline acne. Mupirocin ointment penetrates well into granulomatous lesions such as interdigital abscesses. Owners can decrease the relapse rate and severity of recurrent pyoderma if they immediately apply mupirocin every 12 hours when they first notice early lesions developing. For most cases of pyoderma 3 to 6 weeks of therapy are required for a clinical cure; and some dogs require chronic low-dose or pulse-dose therapy with amoxicillin/clavulanic acid, cloxacillin, or a cephalosporin for control of recurrent pyodermas. Enrofloxacin, difloxacin, marbofloxacin, and orbifloxacin are first choices only for antimicrobial therapy of deep pyodermas and short-term therapy of recurrent pyoderma when resistance has developed. They have excellent activity against S. intermedius, Pseudomonas spp., and Proteus spp., the organisms most likely to be involved in refractory cases. Fluoroquinolones have ideal pharmacokinetic properties; they accumulate in leukocytes and retain activity in necrotic and purulent debris. Since they are concentration-dependent killers, high-dose once-daily administration is ideal and increases client compliance with the treatment regimen. Fluoroquinolone therapy should be avoided for chronic low-dose or pulse-dose therapy because chromosomal-mediated resistance occurs with chronic exposure.

Respiratory Tract Infections Upper Respiratory Tract Primary bacterial infection of the upper respiratory tract is uncommon, but almost all dogs and cats with a mucopurulent or purulent nasal discharge have some bacterial component to their disease. Bordetella bronchiseptica can cause primary upper respiratory tract (URT) infections in dogs; whereas B. bronchiseptica, Mycoplasma spp., and Chlamydophila felis cause primary URT infections in the cat. Most cases of bacterial rhinitis are secondary to

1228

Section  XIII  Infectious Diseases and the fluoroquinolones (­enrofloxacin, orbifloxacin, difloxacin, marbofloxacin). B. bronchiseptica typically is susceptible to amoxicillin-clavulanic acid, tetracyclines, or azithromycin; but some isolates are resistant to the fluoroquinolones. Gram-positive cocci are frequently susceptible to amoxicillin/clavulanic acid, chloramphenicol, cephalosporins, or azithromycin. Aminoglycosides or enrofloxacin can be administered concurrently with parenteral formulations of penicillins or cephalosporins for broad-spectrum treatment of seriously ill patients. Clindamycin or metronidazole can be added to provide activity against β-lactamase– producing Bacteroides fragilis.

other diseases and caused by the variety of normal flora found in the nasal passages; culture and susceptibility test results are difficult to interpret. Treating the bacterial infection without correcting the underlying cause is very unrewarding and encourages emergence of antimicrobial-resistant pathogens such as P. aeruginosa. Chronic URT infection may lead to sinus osteomyelitis. Empiric therapy for URT infections in dogs and cats includes amoxicillin/clavulanate, cephalexin or cefadroxil, or drugs with efficacy against Mycoplasma spp. and C. felis such as doxycycline, azithromycin, or a fluoroquinolone. Doxycycline is considered the most effective therapy for chlamydiosis, but clinical signs improve with any of these therapies, and cats frequently remain polymerase chain reaction or immunofluorescent antibody test positive. Doxycycline is often avoided in young animals because of fears of causing dental damage. Even in children, doxycycline is the least likely of the tetracyclines to cause dental damage, and there are no published reports of dental abnormalities from the use of doxycycline in puppies and kittens. However, oral administration to cats is associated with esophageal damage that can lead to stricture; thus administration of tablets or capsules should be followed with food or water to ensure passage into the stomach. Fluoroquinolones should be reserved for serious infections based on of culture and susceptibility testing. Enrofloxacin should be avoided in cats because of the potential for retinal damage. Tetracycline, chloramphenicol, or erythromycin ophthalmic ointments can be used to treat concurrent conjunctivitis. With chronic infections in dogs or cats, drugs that penetrate bone and target anaerobic bacteria such as amoxicillin/clavulanic acid, clindamycin, or cephalexin or cefadroxil should be chosen.

Prophylactic Antimicrobials Veterinary surgeons routinely use prophylactic antimicrobials in surgical patients undergoing orthopedic procedures, but little evidence from clinical trials demonstrates the efficacy of this practice. In humans undergoing clean bone surgery, antimicrobials are administered intravenously from 30 minutes before skin incision to no longer than 24 hours after the operation. Cefazolin typically is the prophylactic antimicrobial therapy of choice in small animal practice. However, in the only published veterinary trial of prophylactic antimicrobial therapy in dogs undergoing elective orthopedic surgery, prophylaxis decreased the postoperative infection rate, but potassium penicillin G was as efficacious as cefazolin (Whittem et al., 1999). Prophylactic antimicrobial therapy should be followed by close observation and treatment with appropriate antimicrobials and surgery if postoperative infection is diagnosed.

Lower Respiratory Tract Bacterial pneumonia in dogs and cats is usually secondary to some pathologic process that disrupts normal pulmonary defence mechanisms. Treatment choices are dictated by the specific etiology and the clinical status of the patient. In dogs with community-acquired bacterial infections the likely causative pathogens are B. bronchiseptica, Mycoplasma spp., Streptococcus zooepidemicus, Pasteurella spp., and E. coli. In cats the pathogens are similar, with the addition of C. felis. In previously ill animals or animals with hospital-acquired illness, E. coli, Klebsiella spp., Pasteurella spp., streptococci, staphylococci, anaerobes, B. bronchiseptica, Pseudomonas spp., and Mycoplasma spp. are frequently involved; and more than one bacterial pathogen is commonly isolated. The unpredictable antimicrobial susceptibility of E. coli and other gram-negative bacteria makes it difficult to choose antimicrobial therapy without susceptibility testing, thus sampling the lower respiratory tract for culture and sensitivity and cytology is strongly recommended. The critically ill patient should be started on a broad-spectrum, parenteral antimicrobial regimen as soon as possible until results of definitive cultures are obtained. Gram-negative rods frequently are susceptible to potentiated sulfonamides, gentamicin, chloramphenicol, cefpodoxime proxetil,

Septic Arthritis, Tenosynovitis, Osteomyelitis Because of the variety of pathogens involved in musculoskeletal infections, appropriate samples must be submitted for culture and susceptibility testing. Aggressive antimicrobial therapy should be initiated as soon as there is sufficient evidence of infection because of the devastating consequences of bone, joint, or tendon sheath infections. While awaiting culture results, initial antimicrobial selection can be chosen based on clinical case characteristics. In adult dogs and cats, septic arthritis and tenosynovitis commonly result from wounds or iatrogenic contamination with bacteria. In wounds a variety of gram-positive and gram-negative bacteria typically are present, whereas Staphylococcus aureus and S. intermedius are the usual isolates from iatrogenic infections, with methicillin-resistant S. aureus increasingly reported from veterinary cases. Osteomyelitis in dogs and cats is most commonly caused by S. intermedius. Polymicrobial infections are common in small animals and may include mixtures of streptococci, enterococci, Enterobacteriaceae (E. coli, Klebsiella spp., Pseudomonas spp.) and anaerobic bacteria. Cat fight abscesses typically are caused by Pasteurella multocida. Pseudomonas spp. often colonize devitalized tissues such as those occurring with “big dog–little dog” degloving injuries. For most bone and joint infections caused by β-lactamase–producing ­staphylococci,

Musculoskeletal Infections



Chapter  266  Rational Empiric Antimicrobial Therapy

c­ ephalosporins (cefazolin, cephalexin, cefpodoxime proxetil), clindamycin, or amoxicillin-clavulanic acid are effective. Clindamycin and metronidazole are used for anaerobic infections. The aminoglycosides (amikacin, gentamicin) and fluoroquinolones (enrofloxacin, orbifloxacin, difloxacin, marbofloxacin) typically have good activity against staphylococci and excellent activity against gram-negative pathogens. Although amikacin usually has good activity against Pseudomonas spp., it has poor activity against streptococci compared to gentamicin. Because nephrotoxicity and ototoxicity are related to duration of treatment, the aminoglycosides are often reserved for treatment of musculoskeletal infections by local delivery techniques. The excellent broad-spectrum antimicrobial activity, good safety profiles, and availability of injectable (enrofloxacin) and oral formulations of fluoroquinolones make them popular choices for treatment of musculoskeletal infections. The newer human macrolide antimicrobials (azithromycin, clarithromycin) may also be efficacious for musculoskeletal infections and have good safety profiles in dogs and cats.

Septicemia/Bacteremia Septicemia is common in critically ill canine and feline patients, and the majority that are septicemic have positive blood cultures for bacteria. In dogs gram-negative bacteria (especially E. coli) are most common, followed by gram-positive cocci and anaerobes. Polymicrobial infections are also common and usually involve gram-negative

1229

enterics and anaerobes. Bacteria cultured from cats are primarily gram-negative enterics or anaerobes. Therefore it is common to use intravenous β-lactam/aminoglycoside or β-lactam/enrofloxacin combinations for initial therapy of septic dogs and cats. The concentration-dependent drugs are administered once daily, but the time-dependent β-lactam drugs must be administered either by constant rate infusion or at least every 6 hours. Cefoxitin is a secondgeneration cephalosporin with good activity against anaerobes and gram-negative enterics that can be used in septic dogs and cats. Imipenem, meropenem, and vancomycin occasionally are used to treat resistant infections in severely ill dogs and cats; but because of their importance in human medicine their use should not be routine in veterinary patients.

References and Suggested Reading Giguere S et al: Antimicrobial therapy in veterinary medicine, ed 4, Ames, 2006, Iowa State University Press. McKellar QA, Sanchez Bruni SF, Jones DG: Pharmacokinetic/ pharmacodynamic relationships of antimicrobial drugs used in veterinary medicine, J Vet Pharmacol Ther 27:503, 2004. Wilson BJ et al: Susceptibility of bacteria from feline and canine urinary tract infections to doxycycline and tetracycline concentrations attained in urine four hours after oral dosage, Aust Vet J 84:8, 2006. Whittem TL et al: Effect of perioperative prophylactic antimicrobial treatment in dogs undergoing elective orthopedic surgery, J Am Vet Med Assoc 215:212, 1999.

C hapter 

267

Rational Use of Glucocorticoids in Infectious Disease Adam Mordecai, Buffalo Grove, Illinois Rance K. Sellon, Pullman, Washington

E

vidence supporting the use of glucocorticoids in the face of infections in small animal patients is based on anecdotal or retrospective reports. Few prospective controlled studies have critically evaluated the benefits or consequences of glucocorticoid use in this setting. Frequently cited reasons for administration of glucocorticoids in treating infectious disease include suppression of harmful inflammatory or immune responses and suppression of presumed secondary immune-mediated processes. Despite the fact that there is little scientific evidence that supports their use, glucocorticoids are frequently suggested for patients with infectious disease. The aim of this chapter is to review the use of glucocorticoids for infections and to offer guidelines for their use. This chapter does not specifically address the use of glucocorticoids, either topical or systemic, in patients with ocular infections or ocular manifestations of infectious disease, although they are used frequently (see Section XII).

Mechanism of Action The mechanisms by which glucocorticoids mediate antiinflammatory activity are not understood completely (also see Chapter 89). Glucocorticoids first diffuse across the plasma membrane and bind to specific glucocorticoid receptors in the cytoplasm. The steroid-receptor complex then exerts a variety of effects. The complex can inactivate proinflammatory transcription factors and increase the production of proteins that inhibit cytokine production. Glucocorticoids can also mediate their actions through nontranscriptional means such as decreasing the half-life of messenger ribonucleic acid for inflammatory cytokines. Glucocorticoids attenuate inflammation by inducing lipocortin-1, which directly inhibits phospholipase A2, an enzyme that is responsible for production of inflammatory prostaglandins, leukotrienes, and eicosanoids. Through these and other mechanisms inflammation and immune function can be altered or suppressed by glucocorticoids. Both the cellular and humoral arms of the immune system can be affected; however, the cellular response is thought to be most compromised. Poor cellular immune responses could enhance the pathogenic potential of some infectious organisms, prevent cell-mediated clearance of organisms, and perpetuate inflammation secondary to persistence of organisms and activation of other inflammatory pathways. Glucocorticoids are commonly thought to decrease phagocytic and oxidative functions of phagocytic cells in a dose-dependent manner, thereby compromising the ability to kill ingested organisms. It is 1230

these general properties that not only support the use of glucocorticoids in patients with infectious disease but also raise concerns about the potential side effects and complications associated with their use.

Glucocorticoids in Humans with Infectious Disease A survey of the human literature on the use of glucocorticoids as adjunctive treatment for infectious disease puts into perspective many of the uncertainties. Conclusions regarding the benefits of glucocorticoids given to humans with infectious disease vary, depending on the infectious agent studied, the age of the patient group studied, the dose and/or duration of glucocorticoid therapy, the parameters assessed (e.g., immunologic or infectious agent parameters such as cytokine levels or quantity of infectious agent detected), the presence of other infectious agents, and by extension, perhaps, of other concurrent diseases. Human immunodeficiency virus-1 imposes its own perturbations on immune and inflammatory responses. Many of the case reports either involve small numbers of patients or lack appropriate controls. To illustrate, placebo-controlled studies of children with viral respiratory infection treated with glucocorticoids found benefit when treated with several days of prednisone but no benefit in studies in which a single dose of dexamethasone was given at admission. Glucocorticoids have also been shown to be of benefit in humans with peritonsillar abscesses and to improve survival with mycobacterial meningitis, but they do not prevent postrecovery disability. Interestingly, one study of glucocorticoid treatment of humans with mycobacterial meningitis suggests that the clinical benefits may be from mechanisms other than antiinflammatory or immune modulation after finding no difference in a number of inflammatory and immunologic parameters in placeboand glucocorticoid- treated groups. Low doses of glucocorticoids generally are accepted as beneficial in people with sepsis, whereas high doses appear to offer no benefit.

Glucocorticoids in Small Animals with Infectious Disease Respiratory Infections It has been proposed that antiinflammatory doses of glucocorticoids for 5 to 7 days may be effective in ameliorating cough associated with uncomplicated infectious



Chapter  267  Rational Use of Glucocorticoids in Infectious Disease

tracheobronchitis but do not significantly shorten the clinical course of disease. It is commonly recognized that following initial administration of antifungal agents to patients with fungal pneumonia (i.e., blastomycosis and histoplasmosis) respiratory signs can worsen as a consequence of heightened inflammation associated with fungal death. Glucocorticoids are thought to prevent treatment-induced inflammation from occurring; however, as yet there are no studies showing this benefit. In a retrospective study of chronic histoplasmosis in dogs (Schulman, et al., 1999), clinical signs of coughing from airway obstruction associated with hilar lymphadenomegaly resolved more quickly when treated with immunosuppressive dosages (2 to 4 mg/kg/day) of prednisone alone or prednisone and antifungal drugs compared to those in dogs treated with antifungal chemotherapy alone (less than 3 weeks compared to approximately 9 weeks). In this study the glucocorticoid-treated dogs did not show evidence of dissemination of disease.

Central Nervous System Infections In central nervous system (CNS) infections inflammatory mediators and toxic factors produced by the immune system may be more responsible for CNS damage than the primary pathogen. The treatment of bacterial organisms can result in their lysis and release of inflammatory cell wall components, including lipopolysaccharides and outer membrane vesicles. As yet there are no controlled studies addressing the use of glucocorticoids in dogs or cats with infectious meningitis, but anecdotal experience, case reports, and the human literature suggest a potential benefit. At our institution patients suspected to have CNS infection based on cerebral spinal fluid (CSF) pleocytosis, elevated CSF protein content, and/or consistent magnetic resonance imaging findings are treated with a broad-­spectrum antiinflammatory protocol (trimethoprim sulfa, 15 mg/kg BID; clindamycin, 12.5 mg/kg BID; prednisone, 0.5 mg/kg BID) while awaiting more definitive results, including bacterial culture and viral and protozoal titers. Diagnostic testing should always be performed before any treatment since it may affect CSF analysis and culture results. In addition, glucocorticoids may attenuate the increased blood-brain barrier permeability that results from inflammation, thereby theoretically reducing antimicrobial penetration into the CSF. Clinical studies in small animals with bacterial meningitis that address antibiotic penetration in the face of glucocorticoids are lacking, and long-term consequences of glucocorticoid therapy for infectious meningitis have not been established.

Disseminated/Miscellaneous Infections Glucocorticoids are used frequently in conjunction with antimicrobials for hemolytic anemia or thrombocytopenia while awaiting results to differentiate a primary immune-mediated hemolytic process from hemolytic disease secondary to an infectious organism such as Babesia spp. or Mycoplasma spp. Common belief holds that immune-mediated destruction contributes to anemia or thrombocytopenia with these infections and the

1231

addition of glucocorticoids may decrease this ­damage, but there are no controlled studies demonstrating proof of efficacy. In one study glucocorticoid-treated dogs infected by Rickettsia rickettsii–induced Rocky Mountain spotted fever (RMSF) did not show evidence of dissemination of disease (Breitschwerdt, et al., 1997). Because treatment with antimicrobials for RMSF is often effective for improving clinical signs within 1 to 2 days of initiating therapy, the need to use glucocorticoids should be based on a case-by-case basis and is not recommended for routine treatment. Of the many canine and feline infectious diseases, treatment of cats with feline infectious peritonitis (FIP) with glucocorticoids would be a logical application of the drugs, given the key role that immunopathogenesis plays in the clinical disease. Glucocorticoids are often recommended for FIP, despite clinical studies failing to demonstrate the benefits of glucocorticoids. One study has suggested the benefit of concurrent use of recombinant feline interferon and glucocorticoid administration to cats with FIP, but the report included no controls, and the diagnosis of FIP was not confirmed in all cases (Ishida, et al., 2004). Treatment of other systemic infections with glucocorticoids, including Mycoplasma haemofelis, and Babesia canis, has no support in controlled clinical studies, although glucocorticoids are commonly used in the treatment of patients infected with these organisms. Juvenile cellulitis (puppy strangles) is a syndrome of facial swelling, lymphadenopathy, deep pyoderma of the head and face, fever, polyarthritis, anorexia, and depression. The disease is seen most often in young dogs and is attributed to immune-mediated responses to bacterial antigens. Affected patients usually respond to antimicrobials and immunosuppressive doses of glucocorticoids, and available literature provides reasonable (although not case-controlled) evidence for the use of immunosuppressive doses of glucocorticoids in the management of this disease. The disease may recur if corticosteroid therapy is tapered too quickly; thus a slower tapering protocol may be required.

Sepsis/Systemic Inflammatory Response Syndrome/Acute Respiratory Distress Syndrome/Relative Adrenal Insufficiency Systemic inflammatory response syndrome (SIRS) is a term used to describe the clinical consequences of severe systemic inflammation. Severe systemic inflammation can result in secondary conditions such as disseminated intravascular coagulopathy, acute respiratory distress syndrome (ARDS), and multiple organ dysfunction syndrome. Dysregulated systemic inflammation is a major contributor to the morbidity and mortality in sepsis and ARDS. Relative adrenal insufficiency (RAI) is defined as a usually transient lack of response to endogenous or exogenous adrenocorticotropic hormone (ACTH) and occurs in patients with widespread systemic inflammation (also see Chapter 50). Suspicion of RAI is often based on poor systemic pressures despite appropriate hydration (central venous pressures ranging between 5 and 10 cm of water) and vasopressor (dobutamine,

1232

Section  XIII  Infectious Diseases

norepinephrine) dependency. RAI occurs with relative frequency in human septic SIRS patients and has been described recently in septic dogs (Burkitt, et al., 2007). Human studies have demonstrated that a short course of physiologic doses of glucocorticoids improves clinical outcomes in patients with sepsis. It is likely that future studies will show similar benefits for dogs with sepsis and RAI.

Considerations for Glucocorticoid Use Prednisone and prednisolone are ideal glucocorticoids for use in patients with infectious disease because of their short duration of activity (12 to 36 hours). Prednisolone sodium succinate (Solu-Delta-Cortef, Pfizer Animal Health) or methylprednisolone sodium succinate (SoluMedrol, Upjohn) are parenteral formulations that may be used if patients are unable to take oral formulations. Dexamethasone would be an additional alternative for these patients, but its activity is approximately 48 hours, making it perhaps a less ideal first choice. Given its long storage life and because it is relatively inexpensive compared to other glucocorticoids, practitioners may elect to use dexamethasone. Depot formulations such as methyl­ prednisolone acetate (Depo-Medrol, Upjohn) are not ­recommended because of their long duration of activity.

Dosage Systematic evaluation of glucocorticoid dosages in small animal infectious disease patients has not been performed. Typical therapeutic ranges (Table 267-1) to achieve either antiinflammatory or immunosuppressive effects have been suggested. Ideally therapy with glucocorticoids should be initiated at the lowest doses needed to obtain the desired clinical response. Clinicians should be aware of the relative potencies of the commonly used glucocorticoids (Table 267-2) when selecting a glucocorticoid and dose.

Duration of Glucocorticoid Treatment If the correct underlying cause has been identified and antiinfective treatment is effective, clinical improvement usually occurs within days. It is our recommendation that concurrent glucocorticoid therapy should last only as long as needed to achieve and maintain the desired clinical response—in some patients that period may be days, in others weeks. The decision to stop glucocorticoid therapy

depends on the patient’s clinical status, clinician preference, and potential for clinical relapse or deterioration. Common belief holds that glucocorticoid tapering is needed to prevent signs of iatrogenic hypoadrenocorticism. It is our view that tapering is better suited to identify early relapse or recurrence of the syndrome requiring glucocorticoid therapy. If the need arises to acutely stop glucocorticoids, theoretically a clinician should immediately be able to reduce the amount given to a physiologic dose and prevent clinical signs associated with iatrogenic hypoadrenocorticism. Our argument is based on the fact that dogs with glucocorticoid deficiency from spontaneous hypoadrenocorticism fare well with prednisone given at physiologic or slightly higher doses (0.2 to 0.4 mg/kg/day). If the reduction in dose is well tolerated, a brief period of alternate-day therapy should allow return of normal adrenal function. The time period for return of normal adrenal function depends on many variables, including dose, formulation, duration of therapy, and variation in patient response preventing any absolute recommendations. In general, longer durations of therapy with higher doses or use of formulations with greater duration of activity may require a longer period of dose reduction for return of normal adrenal function. Periodic testing in the form of drug cessation trials or ACTH stimulation may be required if iatrogenic hypoadrenocorticism is suspected. A period of dose reduction should also be considered when treating patients concurrently with glucocorticoids and ketoconazole for systemic fungal infections since ketoconazole impairs adrenal glucocorticoid synthesis and could lead to ­transient iatrogenic hypoadrenocorticism.

Adverse Effects of Glucocorticoids With Infectious Disease Apart from the usual side effects of glucocorticoids, there is virtually no information on small animal patients that addresses adverse effects of glucocorticoids when given concurrently with antiinfective therapy. The potential for immunosuppression and exacerbation of existing infection or development of additional infections is a valid concern, yet it seldom seems to be recognized clinically. Perhaps it is more important that the clinician not be lulled into a false sense of security regarding apparent positive responses in patients with infections also treated with glucocorticoids. A patient could improve initially because of antiinflammatory properties and yet worsen with time because of decreased immunologic clearance of infectious organisms and progressive infection, particularly if antiinfective therapy is ineffective. Theoretically

Table 267-1 Glucocorticoid Dosing Recommendations (mg/kg/day) Glucocorticoid

Physiologic Replacement

Antiinflammatory

Immune Suppression

Hydrocortisone Prednisone Dexamethasone

0.5-1.0 0.1-0.2 0.02-0.04

2.5-5 0.5-1 0.1-0.2

Not used 2-4 (dog); 4-8 (cat) 0.4-0.8

Chapter  267  Rational Use of Glucocorticoids in Infectious Disease



Table 267-2 Relative Glucocorticoid Potency of Formulations Likely To Be Used in Patients With Infectious Disease Glucocorticoid Hydrocortisone Prednisone/prednisolone Dexamethasone

Potency Relative to Hydrocortisone 1 5 25

supraphysiologic doses of glucocorticoids could inhibit the inflammation that is necessary for wound repair and retard healing. When adverse effects are suspected secondary to immunosuppression (worsening of disease), rapid reduction of glucocorticoid doses as suggested previously may be required. The etiologic agents of some infections such as endocarditis may be hard to confirm despite appropriate testing (blood cultures, urine cultures). Treatment with glucocorticoids may increase the chance of recovery of an organism such as Bartonella (Dr. Ed Breitschwerdt, personal communication) but glucocorticoids are not advised for that specific intent.

Guidelines for Use of Glucocorticoids with Infections We believe that some patients with infections benefit from treatment with antiinflammatory or occasionally higher doses of glucocorticoids. We suspect that this view is held by many other clinicians despite the absence of rigorous evaluation of glucocorticoid use in small animal infections. When using glucocorticoids in patients with infectious disease, whenever possible we try to adhere to the following guidelines: • Diagnostic studies to identify the specific cause of infection should be completed before the administration of glucocorticoids. • Glucocorticoid treatment should be implemented after or at the same time as antiinfective therapy. • The decision to administer glucocorticoids to patients with an infection should be made on a case-by-case basis that weighs the patient’s clinical status and relative benefits against the potential risks of complications and adverse effects. • Glucocorticoid administration should not form a blanket approach to treatment of a given infectious agent. • Doses of glucocorticoids should be appropriate for the goal of therapy (e.g., antiinflammatory, immunosuppressive, or physiologic replacement for patients with RAI).

1233

• Administration of glucocorticoids with short or intermediate duration of activity (e.g., prednisone) is preferred to glucocorticoids with longer durations of antiinflammatory or immunosuppressive activity; depot forms of glucocorticoids are not advised. • Glucocorticoids should be administered at the lowest dosages and for no longer than needed to achieve and maintain desired clinical responses. • Patients treated with glucocorticoids should be assessed regularly and carefully for complications of therapy, particularly progressive infection. Because glucocorticoid administration can attenuate the very patient responses that alert clinicians to the existence of problems (e.g., fever, pain) that could otherwise suggest clinical deterioration in patients not receiving glucocorticoids, enhanced attention is warranted. • In some patients receiving glucocorticoids concurrently with antiinfective therapy (e.g., those with systemic fungal infections), the duration of the antiinfective treatment period should be extended. • Owners should be advised of the potential risks associated with a treatment approach (glucocorticoids for infection) that lacks support of appropriately performed clinical studies. In summary, predominately anecdotal evidence supports the administration of glucocorticoids to some dogs and cats with infectious disease. Definitive studies that examine the benefits or complications of its use are needed to better characterize the indications and contraindications to the administration of glucocorticoids to such patients.

Suggested Reading Breitschwerdt EB et al: Prednisolone at anti-inflammatory or immunosuppressive dosages in conjunction with doxycycline does not potentiate the severity of Rickettsia rickettsii infection in dogs, Antimicrob Agents Chemother 41:141, 1997. Burkitt JM et al: Relative adrenal insufficiency in dogs with sepsis J Vet Intern Med 21:226, 2007. Ishida T et al: Use of recombinant feline interferon and glucocorticoid in the treatment of feline infectious peritonitis, J Feline Med Surg 6:107, 2004. Minneci PC et al: Meta-analysis: the effect of steroids on survival and shock during sepsis depends on the dose, Ann Intern Med 141:47, 2004. Schulman RL, McKiernan BC, Schaeffer DJ: Use of corticosteroids for treating dogs with airway obstruction secondary to hilar lymphadenopathy caused by chronic histoplasmosis: 16 cases, (1979-1997), J Am Vet Med Assoc 214:1345, 1999. Simmons CP et al: The clinical benefit of adjunctive dexamethasone in tuberculous meningitis is not associated with measurable attenuation of peripheral or local immune responses, J Immunol 175:579, 2005. White SD et al: Juvenile cellulitis in dogs: 15 cases (1979-1988), J Am Vet Med Assoc 195:1609, 1989.

C hapter  

268

Canine Brucellosis Autumn P. Davidson, Davis, California

B

rucellosis is the primary contagious infectious venereal disease of concern in canine reproduction. Brucella canis causes reproductive failure in both the male and female dog. Screening for B. canis is an important part of the prebreeding evaluation of any dog and should be included in the initial diagnostic approach to any case of canine abortion or apparent infertility. Because the incidence of canine brucellosis is low in many parts of the country, breeder compliance with regular testing can wane, making continued veterinary vigilance important.

Etiology and Microbiology Canine brucellosis is caused by B. canis, a small, gram­negative, nonspore forming aerobic coccobacillus. Brucella abortus, Brucella melitensis, and Brucella suis have occasionally caused canine infections but are comparatively very rare. Transmission occurs through direct exposure to bodily fluids (semen, lochia, aborted fetuses/placentas, milk, and less commonly urine containing semen) containing an infectious dose of organism. A large amount of organism is shed in the vulvar discharge of bitches 4 to 6 weeks after abortion. The highest concentration of organism is shed in the semen of infected dogs 2 to 3 months after infection, with lesser amounts shed for years. Urine can serve as a contaminated vehicle because of the proximity of the urinary and genital tracts in the dog. Milk also can serve as a vehicle for shedding. Therefore transmission is primarily venereal and oral (i.e., through the mucous membranes); the latter is associated with the ingestion of infectious materials. Urine and indirect mucous membrane contact are not important routes of transmission. The aerosol route is only important if kennel conditions are very crowded. B. canis is short lived outside the dog and is readily inactivated by common disinfectants such as 1% sodium hypochlorite, 70% ethanol, iodine/alcohol solutions, glutaraldehyde, and formaldehyde. Brucella organisms attach to and penetrate the mucous membranes; virulence is proportional to the infectious dose. After replication in regional lymph nodes, bacteremia occurs within 7 to 30 days after exposure with subsequent transportation to monocyte/macrophage series cells, prostate, uterus, and placenta; B. canis has a predilection for steroid-dependent (reproductive) tissues. It survives facultatively within monocytes and macrophages. Brucella organisms are able to survive and multiply in monocyte/ macrophage cells because they inhibit the bactericidal myeloperoxidase-peroxide-halide system by releasing 5′-guanosine and adenine. Early in infection polymor­ phonuclear cells and macrophages are relatively ineffectual in killing B. canis intracellularly. 1234

Brucella organisms can be identified in the rough endoplastic reticulum of placental trophoblastic giant cells in an infected bitch’s gravid uterus. Severe necrotizing placentitis with infarction of the labyrinth region, coagulation necrosis of the chorionic villi, and necrotizing arteritis result in fetal death. The organism can be found in the gastric contents of the aborted fetuses. Necrotizing vasculitis causing granulomatous lesions results in epididymal and subsequent testicular and prostatic pathology.

Epizootiology Members of the Canidae family are the natural hosts of B. canis; and any mature, reproductively active breed of dog is susceptible to infection. Canine brucellosis occurs most commonly as an outbreak in a large commercial kennel and less commonly in privately owned dogs. Outbreaks of canine brucellosis traditionally have geographic orientation, with increased incidence seen in the southernmost states of the United States and more commonly in Mexico, Central and South America, The People’s Republic of China, and Japan. The incidence in Europe has been low. The increased practice and success of canine semen processing for exportation (chilling and cryopreservation) for the purpose of artificial insemination now makes canine brucellosis a concern worldwide since direct mucosal contact among dogs is no longer necessary for transmission. Humans can become infected with B. canis, although apparently rarely. Approximately 40 cases of human infection have been reported in several countries; however, the actual number is unknown since human cases are rarely diagnosed or, if diagnosed, reported. Transmission to humans most commonly occurs through contact with semen from an infected dog, vulvar discharge from an infected bitch, aborted fetuses or placentas, or direct ­accidental laboratory exposure.

Clinical Signs Canine brucellosis has high morbidity but low mortality. The clinical systemic signs are often subtle and can include suboptimal athletic performance, lumbar pain, lameness, weight loss, and lethargy. The primary clinical sign of brucellosis in the bitch is pregnancy loss, which can occur early (day 20) in gestation, resulting in fetal resorption, or more commonly (approximately 75% of cases) later in gestation (generally 45 to 59 days), resulting in abortion. Bitches with pregnancy loss early in gestation can appear to be infertile unless early ultrasonographic pregnancy evaluation

Chapter  268  Canine Brucellosis

is performed. Nongravid bitches can be asymptomatic or can show regional lymphadenopathy (pharyngeal if orally acquired, inguinal and pelvic if venereally acquired). The primary acute clinical signs of brucellosis in the male dog reflect disease of the portions of the reproductive tract participating in the maturation, transport, and storage of spermatozoa. Epididymitis is common, with associated orchitis, scrotal dermatitis, and resultant deterioration of semen quality and fertility. Chronically testicular atrophy and infertility can occur. The organism can be found in the prostate gland and urine. Antisperm antibodies develop in association with brucellosis-induced epididymal granulomas and further contribute to infertility. Diminished sperm counts (oligospermia), poor sperm motility (asthenospermia), and increased morphologic abnormalities (teratospermia) are characteristic of semen in a Brucella-infected dog. Detached sperm heads, proximal and distal cytoplasmic droplets, and acrosomal deformities are the most common morphologic abnormalities. Sperm head-to-head agglutination suggests the presence of antisperm antibodies. Pyospermia develops 3 to 4 months after infection. An absence of sperm in the ejaculate (azoospermia) can also result. Chronic infections in either sex can result in uveitis, granulomatous splenitis, discospondylitis, granulomatous dermatitis, meningoencephalitis, and nephritis. Bacteremia can persist for years, and asymptomatic dogs can remain infectious for long intervals. Spontaneous recovery can occur 1 to 5 years after infection but is difficult to document. Bitches can produce normal litters subsequent to multiple abortions but can remain infectious to their offspring. Dogs may remain infertile because of irreparable damage to the spermatogenic apparatus.

Diagnosis Serology, blood or tissue culture, histopathology, and polymerase chain reaction (PCR) techniques are appropriate for the diagnosis of canine brucellosis. Common screening serologic tests include the rapid slide agglutination test (RSAT), which uses B. ovis as the antigen; the semiquantitative 2-mercaptoethanol modified RSAT, which substitutes B. canis as the antigen for increased (but not perfect) specificity; the semiquantitative tube agglutination test, in which a titer of 1:200 or greater correlates well with positive blood culture; the indirect fluorescent antibody; the cell wall agar gel immunodiffusion (AGIDcwa); the cytoplasmic agar gel immunodiffusion (AGIDcpa); and the enzyme-linked immunosorbent assay. AGID testing requires trained personnel and special media. Positive serologic results are detected in most dogs within 8 to 12 weeks of infection. Because incubation periods can vary from 2 to 12 weeks, there can be a window of time in which an infected individual may elude serologic diagnosis. Correct interpretation of serologic results is critical to making an accurate diagnosis. Screening serology is sensitive but not specific: a high rate of false positives occurs because surface antigens of B. canis cross-react strongly with antibodies to several other nonpathogenic bacterial species. False-positive rates can be as high as 50% to 60% because of cross-reacting antibodies to Bordetella spp.,

1235

Pseudomonas spp., Moraxella spp., and B. ovis. For patients with positive results on a screening serologic test, confirmatory testing (see following paragraphs) is needed because of the high incidence of false positives. For this reason screening tests are recommended at least 1 month before a planned breeding to give time for more accurate confirmatory testing if the initial screening test is positive. False-negative results with screening serologic tests are very rare. A false negative can occur if a recently infected dog or bitch is less than 8 to 12 weeks postinfective exposure and seroconversion has not yet occurred. Otherwise a negative test is usually indicative of a truly negative dog. Despite improvements in serologic diagnostic methods, confirmatory blood cultures have classically been indicated when the disease is suspected. B. canis is readily isolated from the blood of bacteremic individuals for several months after infection. A positive B. canis culture establishes a definitive diagnosis and has been advocated as the best diagnostic test in the first 2 months of the disease; however, dogs can become abacteremic after 27 to 64 months. B. canis is an aerobe; but, unlike other Brucella spp., the addition of CO2 (5% to 10%) may be inhibitory. Multiplication is slow at the optimum temperature of 37 ° C, and enriched medium (tryptose or trypticase soy media) is needed to support adequate growth. Brucella colonies become visible on suitable solid media in 2 to 3 days. A culture can be identified as belonging to the genus Brucella on the basis of colony morphology, staining, and slide agglutination with anti-Brucella serum. Further classification is best done in a specialized laboratory (Carmichael and Joubert, 1998). In the United States the New York State Diagnostic Laboratory at Cornell University, the Tifton Veterinary Diagnostic and Investigational Laboratory in Georgia, and the University of Florida are recognized as reliable laboratories for definitive testing made necessary by initial positive B. canis screening tests in dogs intended for breeding, for clinically affected dogs undergoing evaluation for infertility or abortion, or when outbreaks are under clinical management. Recently a report of successful PCR identification of B. canis in semen from dogs failing to have organisms microbiologically identified suggests that PCR-based assays may be the most sensitive method of testing. Thus PCR testing could be considered as part of the male dog prebreeding evaluation, especially in cases in which management of an outbreak is the concern (Keid et al., 2007). Brucellosis may be a reportable disease in either the dog or human in certain jurisdictions. Agglutinating antibodies are not protective in the dog.

Therapy Infected dogs and bitches should be removed from breeding programs and neutered to minimize transmission potential. Historically antibiotic therapy has not been rewarding, likely because the organism is intracellular and bacteremia periodic. Antibiotic therapy may reduce antibody titers without clearing the infection. Relapses are common. Combination therapy with tetracyclines (doxycycline or minocycline 25 mg/kg BID orally [PO] for

1236

Section  XIII  Infectious Diseases

4 weeks) and dihydrostreptomycin (10 to 20 mg/kg BID intramuscularly [IM] or subcutaneously [SC] for 2 weeks, week 1 and 4) or an aminoglycoside (gentamicin 2.5 mg/kg BID IM or SC for 2 weeks, week 1 and 4) has been advocated as most successful; but unavailability, ­nephrotoxicity, parenteral therapy requirements, and expense remain problematic (Greene and Carmichael, 2006). Recently one study reported an encouraging outcome of therapy with enrofloxacin (5 mg/kg BID PO for 4 weeks) in a small group of infected dogs and bitches (Wanke, Delpino, and Balth, 2006). Enrofloxacin was not completely efficacious in eliminating B. canis, but it maintained fertility and avoided the recurrence of abortions, transmission of the disease to subsequently whelped puppies, and dissemination of microorganisms during parturition.

Prevention Attempts to develop an appropriate vaccination capable of inducing immunity yet not provoking serologic responses that interfere with the diagnosis have not been successful. Presently the development of a vaccination is considered undesirable since the Brucella vaccinations evaluated to date have offered only moderate protection and immunized dogs have developed antibodies confounding the serodiagnosis. Prevention of infection and elimination of infected dogs should be the principal control strategy in kennels. Prevention requires annual testing of all breeding stock and the testing of all dogs to be introduced into a kennel. Ideally two negative screening tests should be obtained at least a month apart before a dog or bitch is introduced into a breeding facility. Confirmed positive dogs should be isolated (euthanasia is advised by many authors),

­ eutered, treated, and tested monthly (AGID, culture, or n PCR) until two consecutive negative tests occur, recognizing that occult infection can still be present. Private breeders should require screening tests of all bitches presented for breeding and negative results on confirmatory tests if positive results occur during screening before accepting a bitch into their kennel. Stud dogs should be screened appropriately at least annually. Because of the potential for oral transmission, screening of maiden dogs and bitches before breeding is also recommended.

References and Suggested Reading Barr SC et al: Brucella suis biotype 1 infection in a dog, J Am Vet Med Assoc 189(6):686, 1986. Carmichael LE, Joubert JC: Transmission of Brucella canis by contact exposure, Cornell Vet 78:63, 1998. Greene CE, Carmichael LE: Canine brucellosis. In Greene CE, editor: Infectious diseases of the dog and cat, ed 3, Philadelphia, 2006, Saunders, p 369. Hollet RB: Canine brucellosis outbreaks and compliance, Theriogenology 66(3):75, 2006. Johnson CA, Walker RD: Clinical signs and diagnosis of Brucella canis infection, Compend Contin Educ Pract Vet 14:763, 1992. Keid LB et al: A polymerase chain reaction for the detection of Brucella canis in semen of naturally infected dogs, Theriogenology 67(7):1203, 2007. Shin SJ, Carmichael LE: Canine brucellosis caused by Brucella canis. In Carmichael L, editor: Recent advances in canine infectious diseases, Ithaca NY, 1999, International Veterinary Information Service. Wanke MM, Delpino MV, Balth PC: Use of enrofloxacin in the treatment of canine brucellosis in a dog kennel (clinical trial), Theriogenology 66(7):1573, 2006.

C hapter 

269

Leptospirosis Kenneth R. Harkin, Manhattan, Kansas

C

anine leptospirosis has been considered a reemerging infection in the United States beginning in the mid-1990s. Similarly, leptospirosis is considered the most globally widespread zoonotic disease, with recent increases in human cases acquired in all settings. Beginning in 2003 and continuing through 2005, an outbreak of canine leptospirosis in Colorado emphasized the need for continued vigilance in recognizing clinical leptospirosis, even in areas where the disease is considered rare. The purpose of this chapter is to present updated information on leptospirosis and discussions of controversial aspects rather than provide a comprehensive overview of the disease.

Epidemiology Leptospirosis is maintained in domestic and wildlife reservoir hosts in which renal colonization occurs. Leptospiruria results in contamination of surface water, which can include not only lakes, rivers, ponds, and streams but also muddy fields, water bowls, birdbaths, and other stagnant water sources. The prolonged phase of renal colonization and leptospiruria in maintenance hosts, particularly burrowing rodents, is responsible for survival and transmission of the organism in even inhospitable desert environments. Peridomestic wildlife reservoirs, including raccoons, opossums, voles, rats, and other rodents, are the most important in the transmission of disease to dogs in suburban and urban areas, particularly for serovar Grippotyphosa. Endemic infections in cattle and swine herds, along with wildlife, are important in disease transmission to dogs in rural environments. Based on serologic surveys, Grippotyphosa appears to be the most prevalent infecting serovar of dogs in the United States, although a retrospective study identified Pomona and Bratislava as the most prevalent serovars infecting dogs in northern California, with no significant number of Grippotyphosa infections. Another recent serologic survey (Moore et al., 2006) suggested that serovar Autumnalis was now most prevalent, at least for exposure. However, there are questions as to the relevance of titers to serovar Autumnalis. In a recent study (Barr et al., 2005) dogs that were vaccinated with a leptospirosis vaccine containing serovars Grippotyphosa and Pomona developed elevated titers to serovar Autumnalis without concomitant equivalent increases in titers to serovar Grippotyphosa. The rise in serologically documented cases of Autumnalis correlates with the inclusion of serovars Grip­potyphosa and Pomona in the leptospirosis vaccine, and the seropositivity to Autumnalis correlates strongest to serovar Pomona. These findings support the possibility that the increase

in positive titers to serovar Autumnalis is a reflection of vaccination and not a true increase in Autumnalis infection rates. A number of retrospective studies have consistently shown that the vast majority of cases (≈80%) are diagnosed between July and December and most are in dogs in suburban and rural environments. Large-breed dogs are more commonly affected, likely because of the tendency for them to be outside and participating in activities that increase their exposure; and there is a possible breed predisposition in the German shepherd. The potential predisposition for German shepherds has been identified in a number of studies (Ward et al., 2002). A possible explanation for this breed predisposition is suggested by an investigation of human triathletes who contracted leptospirosis in Illinois and Wisconsin. That study documented that humans with the major histocompatibility (MHC) phenotype HLA DQ6 were at greater risk of infection than individuals who did not carry the phenotype. It is also possible that the predisposition for German shepherds is associated with immunoglobulin A deficiency, a relatively common problem in the breed and not a specific MHC phenotype.

Disease Syndromes Acute renal failure is the most commonly recognized disease syndrome in dogs, accounting for more than 90% of reported cases. These dogs often present with anorexia, depression, and vomiting and may also demonstrate arthralgia or myalgia, icterus, polyuria and polydipsia, dyspnea from pulmonary hemorrhage or pneumonitis, and oculonasal discharge. Uveitis may be subtle and is present in a large number of dogs with acute renal failure from leptospirosis. Uveitis goes unrecognized in most dogs, particularly when a qualified ophthalmologist is not available for consultation. Hepatic failure occurs concurrently in 10% to 20% of dogs with acute renal failure but may also be present independently. These dogs typically have moderate-to-marked elevations in serum alanine transaminase (ALT), serum alkaline phosphatase (ALP), and bilirubin, although ALP elevations are typically higher than ALT elevations. Polyuria and polydipsia may occur in the absence of azotemia or any other laboratory abnormalities, and dogs may appear relatively healthy despite their profound polyuria. Urine specific gravity in these dogs is often hyposthenuric, and the urine sediment is usually inactive. The profound polyuria is often misdiagnosed as central diabetes insipidus. Marked fever (often in excess of 40 ° C) of 2 to 4 days’ duration in the absence of clinicopathologic abnormalities often occurs days to weeks 1237

1238

Section  XIII  Infectious Diseases

before the onset of nonazotemic polyuria and polydipsia. Less commonly seen syndromes include intestinal intussusceptions, pleural and pericardial effusion, transverse myelitis, and meningitis.

Outer Membrane Proteins The outer membrane proteins (OMPs) of pathogenic leptospires play a critical role in pathogenicity and development of the host immune response. Antibodies produced to specific proteins are currently under investigation as diagnostic markers, opening up the possibility of commercial diagnostic tests that do not rely on maintenance of stock cultures of leptospires. The expression of certain OMPs is down-regulated in infection, suggesting that they play a role in survival of the organism outside of the host, but would have no usefulness in vaccine development or serodiagnosis. However, the expression of other OMPs is up-regulated during infection, and these OMPs are potential candidates for vaccine development and diagnostic tests. LipL32, which may be a hemolysin, is the major OMP of pathogenic leptospires and is expressed both in vitro and in vivo. Its expression is conserved in pathogenic leptospires, and antibodies to LipL32 are consistently identified in sera from infected patients. Although it is immunogenic, LipL32 does not appear to confer protective immunity independently of other OMPs. The transmembrane protein OmpL1 and lipoprotein LipL41 are also conservatively expressed in pathogenic leptospires during infection. Independently they do not confer immunity, but when combined they have a synergistic effect that provides protective immunity. Lig A and Lig B are immunoglobulin-like proteins that can confer protective immunity independently, are up-regulated during infection, and have great promise as vaccine candidates. Their role in pathogenicity is unclear, but leptospires that lose their Lig proteins and lig ribonucleic acid transcript expression lose their virulence.

Diagnosis Leptospirosis should be considered as one of the primary differential diagnoses for any dog that presents with acute renal failure for which the cause is not immediately identified (e.g., ethylene glycol poisoning, pyelonephritis, or aminoglycoside administration). In addition, for any of the previously described disease syndromes of leptospirosis, failure to consider leptospirosis will result in a failure to diagnose. The microscopic agglutination test (MAT) remains the gold standard for the diagnosis of leptospirosis. Most veterinary diagnostic laboratories in the United States evaluate for antibodies against serovars Canicola, Icterohaemor­ rhagiae, Grippotyphosa, Pomona, and Hardjo; many also include Bratislava and a few include Autumnalis. Titers of at least 1:800 are supportive of a diagnosis when compatible clinical findings are present, but documentation of a fourfold rising titer over a 2- to 4-week interval is preferred to confirm the diagnosis. When a 2-week convalescent titer is not convincing, a 4-week titer is recommended for confirmation of infection. Identification of

the infecting serovar is not important for therapy but may have epidemiologic significance, especially during ­outbreaks of disease. Interpretation of the MAT can be complicated by cross-reactivity, often resulting in equivalently elevated titers to multiple serovars, although the infecting serovar usually provokes the most persistently elevated titer over time. Coinfection with multiple serovars has not been documented. Prior vaccination may also complicate the interpretation of titers obtained by the MAT. Dogs that have been vaccinated recently may have titers as high as 1:3200. Although vaccinal titers often wane within 3 to 4 months, some dogs may have persistently elevated titers. As discussed previously, dogs that have been vaccinated may have elevated titers to nonvaccinal serovars, further complicating the diagnosis. In some cases of leptospirosis dogs may not develop a titer, either because the infecting serovar is not included on the MAT panel or the dog just does not develop an appropriate antibody response. Other diagnostic tests may be necessary in these instances. The polymerase chain reaction (PCR) assay has promise in the diagnosis of leptospirosis and is available at a number of veterinary diagnostic laboratories. The diagnostic sample of choice is urine (a minimum of 3 to 6 ml is recommended), which can be obtained by free catch, catheterization, or cystocentesis. Other samples (e.g., aqueous humor, fresh kidney or liver, semen, blood, or cerebrospinal fluid) can be evaluated by PCR but are not submitted routinely. There is no appreciable degradation of leptospiral deoxyribonucleic acid (DNA) when the sample is held at room temperature for 72 hours; but, because of the possibility of shipping delays and seasonal high temperatures, the sample should be sent by next-day or 2-day carrier with an ice pack. A positive result indicates that leptospiral DNA was identified in the sample, supporting the diagnosis of leptospirosis. The immune system is efficient at rapidly removing dead leptospires from the kidney; thus, even though it is possible that the PCR is identifying dead leptospires, it is more likely that the sample contains live leptospires. Although the possibility of false-positive results exists from sample contamination, this is an unlikely event in most laboratories. The PCR has the advantage of sensitivity, becoming positive before seroconversion in some dogs, a finding that was confirmed in humans when various tests for the diagnosis of leptospirosis were compared, although most dogs are positive by both serology and PCR when evaluated. Dogs with leptospirosis may have a negative PCR if the number of leptospires in the sample is below the limit of detection of the test, if PCR is performed before establishment of leptospiruria, or if the patient had been treated with appropriate antibiotic therapy before testing. Dogs that are initially PCR positive in the urine will usually still be positive if tested 3 days after initiating intravenous ampicillin therapy. Unlike the MAT, the PCR fails to identify the infecting serovar but is specific for pathogenic leptospires. Fluorescent-antibody (FA) testing, aimed at identifying the leptospiral organism in urine or tissue, is available at some veterinary diagnostic laboratories. Although the sensitivity of FA testing is better than dark-field

Chapter  269  Leptospirosis

­ icroscopic evaluation of urine or silver staining of tism sue, its sensitivity does not match that of PCR. Likewise, nonspecific binding of the antibody may result in falsepositive results. A number of diagnostic tests, including dark-field microscopy (low sensitivity), silver staining of tissues (low sensitivity and specificity), and culture (low sensitivity, requires special media) have very little use to most veterinarians. I recommend the combination of the MAT and PCR for optimizing the diagnosis of leptospirosis.

Therapy There are two main components of therapy for leptospirosis: supportive and specific. Supportive therapy for dogs with acute renal failure from leptospirosis traditionally centers on fluid therapy. Polyuric renal failure is more common than oliguric or anuric renal failure, simplifying fluid management. When oliguric or anuric renal failure ensues, management of fluid therapy becomes more complex. Both hemodialysis and peritoneal dialysis have been used successfully in the management of oliguric and anuric renal failure caused by leptospirosis. The cornerstone of specific therapy is the administra­ tion of an appropriate antibiotic. Traditionally ampicillin is used initially in the dog acutely ill with leptospirosis. Recommended ampicillin dosages range from 22 to 40 mg/kg intravenously every 6 to 8 hours, although 25 mg/kg intravenously every 8 hours appears safe and effective. Ampicillin should eliminate the leptospiremic phase but does not eliminate the organism from the renal tubules. The recommendation to continue amoxicillin once oral administration can be tolerated appears rooted in the past treatment standard of penicillin therapy for 2 weeks followed by 2 weeks of dihydrostreptomycin. Dihydrostreptomycin therapy was directed at eliminating the leptospiruric phase but was delayed until full recovery from renal failure was achieved. Doxycycline eliminates all phases of leptospiral infection and does not carry the nephrotoxic potential seen with other tetracyclines. Although it would be appropriate to administer doxycycline intravenously from the point of initial diagnosis, I still prefer to administer ampicillin initially in acutely ill dogs and then transition to doxycycline at 5 mg/kg orally every 12 hours as soon as oral medications can be tolerated. A treatment course with doxycycline of 3 to 4 weeks is recommended. Dogs with leptospirosis that are not vomiting can be administered doxycycline orally as the first-line of therapy. Ciprofloxacin has been shown to be effective in the treatment of leptospirosis (improved survival versus the untreated group), and it is suspected that other fluoroquinolones would be equally effective. However, ofloxacin was ineffective in eliminating renal infection in a hamster model of leptospirosis; thus fluoroquinolones may not be an acceptable substitute for doxycycline. The ability of the fluoroquinolones to cross the blood-brain barrier may make them attractive for parenteral use when uveitis or meningitis is present. Although most dogs stop shedding leptospires in the urine soon after beginning doxycycline therapy, I have followed three dogs that remained PCR

1239

positive for leptospires in the urine for prolonged periods (>60 days) and became PCR negative only after the administration of enrofloxacin at 5 mg/kg orally every 12 hours. In specific situations the use of corticosteroids (dexamethasone, 0.25 mg/kg intravenously [IV] q12h; or prednisone, 2 mg/kg orally [PO] q24h) may be indicated in the management of leptospirosis. Although thrombocytopenia is typically mild (80,000 to 120,000/μL), in the rare case that develops severe thrombocytopenia (4 years) with fewer relapses (Slappedel and Teske, 1999). Treatment of dogs with these compounds requires frequent monitoring, especially of renal function because of potential ­nephrotoxicity in dogs that frequently already have renal disease. Additional drugs that show some effectiveness in treatment of leishmaniasis are amphotericin B (desoxycholate, lipid emulsion and liposomal preparations), ­miltefosine, pentamidine, and aminosidine (Noli and Auxiliz, 2005). Parasitic cures are uncommon with these products, but clinical improvements do result. A recent in vitro study with marbofloxacin could hold promise for a less toxic treatment of leishmaniasis. Until a definitive mode of transmission is identified in North America, dogs should not be held under crowded conditions, and effective topical insecticides should be used to minimize exposure to possible insect vectors. A commercial vaccine against canine visceral leishmaniasis has been licensed in Brazil and contains the Fucose-Mannose-ligand antigen of Leishmania donovani (Nogueira, 2005). This product has proven effective in reducing infection rates in dogs and humans where visceral leishmaniasis is endemic (LeishmuneR, Fort Dodge Saude Animal Ltd.).

1254

Section  XIII  Infectious Diseases

References and Suggested Reading Baneth G: Leishmaniases. In: Greene CE, editor, Infectious diseases of the dog and cat, ed 3, St. Louis, 2006, Saunders p.685. Breitschwerdt EB, Schantz P: Canine visceral leishmaniasis in North America. In Greene CE, editor: Infectious diseases of the dog and cat, ed 3, St Louis, 2006, Saunders, p 696. Ferrer L: Leishmaniasis. In Kirk RW, Bonagura JD, editors: Current veterinary therapy XI (small animal practice), Philadelphia, 1992, Saunders, p 266. Gaskin AA et al: Visceral leishmaniasis in a New York foxhound kennel, J Vet Intern Med 16:34, 2002. Nogueira FS et al: LeishmuneR vaccine blocks the transmission of canine visceral leishmaniasis: absences of Leishmania parasites in blood, skin and lymph nodes of vaccinated exposed dogs, Vaccine 23:4805, 2005. Noli C, Auxiliz ST: Review: treatment of canine Old World visceral leishmaniasis: a systemic review, Vet Dermatol 16:213, 2005.

C hapter  

Oliva G et al: Incidence and time course of Leishmania infantum infections examined by parasitological, serologic, and nestedPCR techniques in a cohort of naïve dogs exposed to three consecutive transmission seasons, J Clin Microbiol 44:1318, 2006. Rosypal AC, Zajac AM, Lindsay DS: Canine visceral leishmaniasis and its emergence in the United States, Vet Clin N Am Sm Anim Pract 33:921, 2003. Rosypal AC et al: Utility of diagnostic tests used in diagnosis of infection in dogs experimentally inoculated with a North American isolate of Leishmania infantum, J Vet Intern Med 19:802, 2005. Schantz et al: Autochthonous visceral leishmaniasis in dogs in North America, J Am Vet Med Assoc 226:1316, 2005. Scalone A et al: Evaluation of the Leishmania recombinant K39 antigen as a diagnostic marker for canine leishmaniasis and validation of a standardized enzyme-linked immunosorbent assay, Vet Parasitol 104:275, 2002. Slappedel RJ, Teske E: A review of canine leishmaniasis presenting outside endemic areas, Proceedings of the International Canine Leishmaniosis Forum, Barcelona, Spain,1999, p 54.

274

Toxoplasmosis Michael R. Lappin, Fort Collins, Colorado

F

amiliarity with Toxoplasma gondii is important for all small animal practitioners because of pet ownership issues, as well as the occasional association of T. gondii with clinical illness in cats and dogs. The life cycle, diagnosis, treatment, and prevention of feline and canine toxoplasmosis has been reviewed extensively over the years (Dubey and Lappin, 2006). In addition, the American Association of Feline Practitioners and the Centers for Disease Control and Prevention have provided information concerning cat ownership as it relates to T. gondii and other infectious agents (Brown et al., 2003; Kaplan, Massur, and Holmes, 2002).* This chapter emphasizes some of the most important points about this disease and provides recently published information concerning the zoonotic and clinical considerations for this protozoan.

* www.aafponline.org/resources/guidelines/ZooFinal2003.pdf www.cdc.gov/ncidod/dpd/parasites/toxoplasmosis/default.htm

Agent and Epidemiology T. gondii is one of the most prevalent parasites infecting warm-blooded vertebrates; a recent survey of clinically ill cats in the United States showed an overall seroprevalence rate of 31.6% (Vollaire, Radecki, and Lappin, 2005). Approximately 20% of dogs in the United States are seropositive for T. gondii antibodies. Only cats complete the coccidian life cycle and pass environmentally resistant oocysts in feces. Dogs do not produce T. gondii oocysts like cats but can mechanically transmit oocysts after ingesting feline feces. Sporozoites develop in oocysts after 1 to 5 days of exposure to oxygen and appropriate environmental temperature and humidity. Thus, to lessen the potential of exposure to T. gondii for veterinary staff members in the laboratory, fresh feces should be used for fecal flotation, or the feces should be stored refrigerated until examined. Tachyzoites are the rapidly dividing stage of the organism; they disseminate in blood or lymph during active infection and replicate rapidly intracellularly until the cell is destroyed. Tachyzoites can be detected



Chapter  274  Toxoplasmosis

1255

in blood, aspirates, and effusions in some dogs or cats with disseminated disease. Bradyzoites are the slowly dividing, persistent tissue stage that form in the extraintestinal tissues of infected hosts as immune responses attenuate tachyzoite replication. Bradyzoites form readily in the central nervous system (CNS), muscles, and visceral organs. T. gondii bradyzoites can be the source of reactivated acute infection (e.g., during immune suppression by feline immunodeficiency virus [FIV] or high-dose cyclosporine therapy), or they may be associated with some chronic disease manifestations (e.g., uveitis). Infection of warmblooded vertebrates occurs following ingestion of any of these three life stages of the organism or transplacentally. Cats infected by ingesting T. gondii bradyzoites during carnivorous feeding shed oocysts in feces from 3 to 21 days. Fewer numbers of oocysts are shed for longer time periods if sporulated oocysts are ingested. Sporulated oocysts can survive in the environment for months to years and are resistant to most disinfectants. For dogs, cats, and humans it is believed that bradyzoites persist in tissues for the life of the host, regardless of whether drugs with presumed T. gondii activity are administered.

Chronic toxoplasmosis with vague and recurrent clinical signs of disease appears to occur in some cats. T. gondii infection should be on the differential diagnoses list for cats with anterior or posterior uveitis, fever, muscle hyperesthesia, weight loss, anorexia, seizures, ataxia, icterus, diarrhea, or pancreatitis. Based on results of T. gondii–specific aqueous humor antibody and polymerase chain reaction (PCR) studies, toxoplasmosis appears to be one of the most common infectious causes of uveitis in cats. It is unknown why the majority of cats infected with T. gondii are subclinically affected and other cats develop clinical signs of disease. Similar to what is reported in humans, kittens infected with T. gondii transplacentally or lactationally commonly develop ocular disease. Immune complex formation and deposition in tissues and delayed hypersensitivity reactions may be involved in chronic clinical toxoplasmosis. Since none of the anti-Toxoplasma drugs totally clear the body of the organism, recurrence of disease is common. This fact should be made clear to owners in discharge instructions, and the communication noted in the medical record.

Clinical Features of Feline Infection

Clinical Features OF Canine Infection

Approximately 10% to 20% of cats that are experimentally inoculated with T. gondii tissue cysts develop selflimiting small bowel diarrhea for 1 to 2 weeks; this is presumed to be caused by local replication of the organism during the intestinal phase of infection. However, detection of T. gondii oocysts in feces is rarely reported in studies of client-owned cats with diarrhea, in part because of the short oocyst shedding period. Although T. gondii enteroepithelial stages were found in intestinal tissues from two cats with inflammatory bowel disease that responded to anti- T. gondii drugs, it is my experience that chronic gastrointestinal disease in cats from toxoplasmosis is uncommon. Fatal toxoplasmosis can develop during acute dissemination and intracellular replication of tachyzoites; hepatic, pulmonary, CNS, and pancreatic tissues are commonly involved (Dubey and Lappin, 2006). Transplacentally or lactationally infected kittens develop the most severe signs of extraintestinal toxoplasmosis and generally die of pulmonary or hepatic disease. Common clinical findings in cats with disseminated toxoplasmosis include depression, anorexia, fever followed by hypothermia, peritoneal effusion, icterus, and dyspnea. If a host with chronic toxoplasmosis is immunosuppressed, bradyzoites in tissue cysts can replicate rapidly and disseminate again as tachyzoites; this is common in humans with acquired immune deficiency syndrome (AIDS). Disseminated toxoplasmosis has been documented in cats concurrently infected with feline leukemia virus (FeLV), FIV, and feline infectious peritonitis virus. Commonly used clinical doses of glucocorticoids do not appear to predispose to activated toxoplasmosis. However, administration of cyclosporine to cats or dogs with renal transplantations or dermatologic disease has been associated with fatal disseminated toxoplasmosis (Bernstein et al., 1999; Last et al., 2004; Barrs, Martin, and Beatty, 2006).

Before 1988 many dogs diagnosed with toxoplasmosis based on histologic evaluation were truly infected with Neospora caninum. However, T. gondii infection frequently occurs in dogs and rarely can be associated with clinical disease. The most common syndromes associated with disseminated toxoplasmosis in dogs have involved the respiratory, gastrointestinal, or neuromuscular systems, resulting in fever, vomiting, diarrhea, dyspnea, and icterus. Disseminated toxoplasmosis is most common in immunosuppressed dogs such as those with canine distemper virus infection or those receiving cyclosporine to prevent rejection of a renal transplant. Neurologic signs depend on the location of the primary lesions and include ataxia, seizures, tremors, cranial nerve deficits, paresis, and paralysis. Dogs with myositis present with weakness, stiff gait, or muscle wasting. Rapid progression to tetraparesis and paralysis with lower motor neuron dysfunction can occur. Myocardial infection resulting in ventricular arrhythmias occurs in some infected dogs. Retinitis, anterior uveitis, iridocyclitis, and optic neuritis occur in some dogs with toxoplasmosis but for unknown reasons seem to be less common than in the cat.

Clinical Diagnosis Cats and dogs with clinical toxoplasmosis can have a variety of clinicopathologic and radiographic abnormalities, but none of the findings alone can be used to document the disease. Nonregenerative anemia, neutrophilic leukocytosis, lymphocytosis, monocytosis, neutropenia, eosinophilia, proteinuria, bilirubinuria, and increases in serum globulins and bilirubin concentration can be seen. In addition, increased activities of creatinine kinase, alanine aminotransferase, alkaline phosphatase, and lipase occur in some affected animals.

1256

Section  XIII  Infectious Diseases

Pulmonary toxoplasmosis most commonly causes diffuse interstitial-to-patchy alveolar patterns or pleural effusion. Cerebrospinal fluid (CSF) protein concentrations and cell counts are often higher than normal; the predominant white blood cells in CSF are small mononuclear cells and neutrophils. The detection of these abnormalities should direct the clinician to perform additional, more specific T. gondii tests, particularly if there is a high likelihood of exposure to sporulated oocysts or uncooked meat or there is historic or other evidence of immunodeficiency. The antemortem definitive diagnosis of toxoplasmosis can be made if the organism or its deoxyribonucleic acid (DNA) is demonstrated; this is most likely to be achieved in cats or dogs with acute disseminated disease. Tachyzoites or bradyzoites have been detected in tissues, effusions, bronchoalveolar lavage fluids, aqueous humor, or CSF. Detection of T. gondii organisms is unlikely in cats or dogs with chronic disease manifestations. T. gondii DNA can be amplified from tissues and fluids; thus PCR detection is considered more sensitive and specific than cytologic or histopathologic detection of the organism. Multiple laboratories offer PCR assays that can amplify DNA of T. gondii and N. caninum (dogs); these assays should be considered if T. gondii or N. caninum is suspected but are not documented cytologically. Tissues, fluids, or aspirates for T. gondii PCR testing can be maintained frozen until assayed because the DNA is very stable. T. gondii PCR assays seem to be less sensitive if performed on formalin-fixed samples; thus use of fresh tissue is preferred. Immunohistochemistry can also be performed on tissues to document the presence of T. gondii and to differentiate T. gondii from N. caninum. Detection of 10 × 12 micrometer diameter oocysts in feces in cats with diarrhea suggests toxoplasmosis but is not definitive since Besnoitia and Hammondia infections of cats produce morphologically similar oocysts. In these cases T. gondii serology should be performed, and, if the primary infection is T. gondii, seroconversion should be documented within 2 to 3 weeks. In dogs N. caninum oocysts are morphologically similar to T. gondii oocysts. These dogs can be screened for N. caninum and T. gondii antibodies in 2 to 3 weeks to determine the organism that was associated with the infection. A multitude of tests for detection of T. gondii–specific antibodies (immunoglobulin [Ig]M, IgG, IgA), antigens, and immune complexes have been evaluated (Dubey and Lappin, 2006). Unfortunately test results can be positive in healthy animals, as well as those with clinical signs of toxoplasmosis; thus it is impossible to make an antemortem diagnosis of clinical toxoplasmosis based on results of these tests alone. Of the serum tests, IgM titers correlate best with clinical toxoplasmosis since this antibody class is rarely detected in serum of healthy animals; thus many laboratories offer IgM and IgG test results separately. The antemortem diagnosis of clinical toxoplasmosis can tentatively be based on the combination of (1) clinical signs of disease referable to toxoplasmosis; (2) demonstration of antibodies in serum, which documents exposure to T. gondii; (3) demonstration of an IgM titer >1:64 or a fourfold or greater increase in IgG titer, which suggests recent or active infection;

(4) exclusion of other common causes of the clinical syndrome; and (5) positive response to appropriate treatment. In dogs gneosporosis and toxoplasmosis appear clinically similar; thus I frequently combine T. gondii and N. caninum serologic tests in my diagnostic workup of suspect patients. Some cats and dogs with clinical toxoplasmosis will have reached their maximal IgG titer or will have undergone antibody class shift from IgM to IgG by the time they are serologically evaluated; thus failure to document an increasing IgG titer or a positive IgM titer does not exclude the diagnosis of toxoplasmosis. This problem is most common in cats and dogs with chronic disease manifestations. Some healthy cats and dogs have extremely high serum antibody titers, and some clinically ill cats and dogs have low serum antibody titers, thus the magnitude of titer is relatively unimportant in the clinical diagnosis of toxoplasmosis. Because the organism cannot be cleared from the body, most cats and dogs will be antibody-positive for life; thus there is no clinical use in repeating serum antibody titers after disease manifestations have resolved. The combination of T. gondii–specific antibody detection in aqueous humor or CSF and organism DNA amplification by PCR is the most accurate way to diagnose ocular or CNS toxoplasmosis in cats. T. gondii–specific IgA, IgG, and DNA can be detected in aqueous humor and CSF of both normal and clinically ill cats; however, T. gondii–­specific IgM has only been detected in the aqueous humor or CSF of clinically ill cats and so may be the best indicator of clinical disease (Lappin MR, Unpublished data). My laboratory has rarely amplified T. gondii DNA or shown T. gondii antibody production in aqueous humor or CSF from dogs. CNS toxoplasmosis and neosporosis can appear clinically similar in dogs; thus I frequently combine PCR testing for both organisms on CSF samples from dogs with inflammatory CNS disease. T. gondii antigens or DNA can be detected in the blood of healthy cats; the source of the organism is likely bradyzoites from tissue cysts. Since T. gondii DNA can be detected in blood of healthy cats, positive PCR results do not always correlate to clinical disease. Whether parasitemia can be documented in more dogs with toxoplasmosis than healthy dogs is currently unknown.

Therapy Supportive care should be instituted as needed. I have used clindamycin hydrochloride administered at 10 to 12 mg/kg orally every 12 hours for 4 weeks or trimethoprim­sulfonamide combination administered at 15 mg/kg orally every 12 hours for 4 weeks most frequently for the treatment of clinical feline or canine toxoplasmosis. These two drugs can also be used in combination. Trimethoprim sulfa is likely to penetrate an intact blood-brain barrier better than clindamycin and thus should be considered for CNS toxoplasmosis, particularly if there is a poor response to clindamycin in the first 7 days of therapy. Azithromycin administered at 7.5 mg/kg orally every 12 hours has been used successfully in a limited number of cats and dogs, but the optimal interval or duration of this expensive drug is unknown. Recently a case of azithromycin-­resistant,

Chapter  274  Toxoplasmosis

clindamycin-responsive ­pulmonic toxoplasmosis in a dog was documented (Lappin MR, unpublished data). It is likely that, just like bacteria, different T. gondii isolates have different antimicrobial susceptibilities; thus, if the first drug attempted fails, an alternate drug should be attempted if the organism is still high on the differential list. Pyrimethamine combined with sulfa drugs is effective for the treatment of human toxoplasmosis but commonly results in toxicity in cats; thus I never use the drug for this purpose. Cats or dogs with systemic clinical signs of toxoplasmosis combined with uveitis should be treated with antiToxoplasma drugs in combination with topical, oral, or parenteral corticosteroids to avoid secondary glaucoma and lens luxations. Prednisolone acetate (1% solution) applied topically to the eye three to four times daily is generally sufficient. T. gondii–seropositive cats or dogs with uveitis that are otherwise normal can be treated with topical glucocorticoids alone unless uveitis is recurrent or persistent. In the latter situation it may be beneficial to administer a drug with anti–T. gondii activity. Clinical signs not involving the eyes or the CNS usually begin to resolve within the first 2 to 3 days of clindamycin or trimethoprim-sulfonamide administration; ocular and CNS toxoplasmosis respond more slowly to therapy. If fever or muscle hyperesthesia is not lessening after 3 days of treatment, other causes should be considered, or an alternate anti–Toxoplasma drug prescribed. Recurrence of clinical signs may be more common in cats treated for less than 4 weeks. In cases of pulmonary toxoplasmosis, total resolution of radiographic abnormalities may not occur for several weeks. The prognosis is usually poor for cats or dogs with hepatic or pulmonary disease resulting from organism replication, particularly in those that are immunocompromised. It is currently unknown whether there is benefit to testing cats or dogs for T. gondii infection and treating the seropositive animals before administering cyclosporine therapy for other clinical diseases. If cyclosporine is to be used, it seems prudent to use the lowest dose possible and to attempt to avoid exposure to T. gondii by restricting hunting activity and feeding processed foods.

Zoonotic Aspects and Prevention T. gondii is an important zoonotic agent. Primary infection of mothers during gestation can lead to clinical toxoplasmosis in the fetus; stillbirth, CNS disease, and ocular disease are common clinical manifestations. Primary infection in immunocompetent individuals results in self-limiting fever, malaise, and lymphadenopathy. As T-helper cells counts decline, approximately 10% of humans with AIDS develop toxoplasmic encephalitis from activation of bradyzoites in tissue cysts. T. gondii is known to alter behavior of prey species, which may benefit the organism by allowing the feline definitive host to more easily ingest the parasite and continue the life cycle. Interestingly there have also been a number of papers suggesting that chronic T. gondii infection of humans may result in a variety of CNS diseases, including behavior changes and schizophrenia (Flegr, 2007; Webster, 2007). However, to date none of the work has documented a definitive link

1257

to toxoplasmosis; and, because T. gondii infection can be acquired in several ways, there is no reason to relinquish a personal cat for this concern. Humans most commonly acquire toxoplasmosis by ingesting sporulated oocysts or tissue cysts or transplacentally. To prevent toxoplasmosis, humans should avoid eating undercooked meats or ingesting sporulated oocysts. Although owning a pet cat has been associated epidemiologically with acquiring toxoplasmosis in some studies, the majority of work suggests that touching individual cats is probably not a common way to acquire toxoplasmosis for the following reasons: (1) cats generally only shed oocysts for days to several weeks following primary inoculation; (2) repeat oocyst shedding is rare, even in cats receiving glucocorticoids or cyclosporine or in those infected with FIV or FeLV; (3) cats with toxoplasmosis inoculated with tissue cysts 16 months after primary inoculation did not shed oocysts; (4) cats are very fastidious and usually do not allow feces to remain on their skin for time periods long enough to lead to oocyst sporulation (the organism was not isolated from the fur of cats shedding millions of oocysts 7 days previously); (5) increased risk of acquired toxoplasmosis was not associated with cat ownership in studies of veterinary health care providers or humans with AIDS. However, since some cats will repeat oocyst shedding when exposed a second time, feces should always be handled carefully. If a fecal sample from a cat is shown to contain oocysts measuring 10 × 12 microns, it should be assumed that the organism is T. gondii. The feces should be collected daily until the oocyst shedding period is complete; administration of clindamycin (25 to 50 mg/kg divided q12h orally [PO]) or sulfonamides (100 mg/kg divided q12h, PO) can reduce levels of oocyst shedding.

Box 274-1 Guidelines for Cat Owners To Avoid Acquiring Toxoplasmosis • Wash hands after handling cats, especially if you are pregnant or immunocompromised. • Remove fecal material from the home environment daily. • If possible, do not have immunocompromised humans clean the litter box. If immunocompromised humans must clean the litter box, they should wear gloves and wash hands thoroughly when finished. • Use litter box liners and periodically clean the litter box with scalding water and detergent. • Wear gloves when gardening and wash hands thoroughly when finished. • Cover children’s sandboxes when not in use to lessen fecal contamination by outdoor cats. • Only feed cats cooked or commercially processed food. • Control potential transport hosts such as flies and cockroaches that may bring the organism into the home. • Filter or boil water from sources in the environment. • Housing cats indoors may lessen their exposure. • Cook meat for human consumption to 80 ° C for 15 minutes minimum (medium-well). • Wear gloves when handling meat and wash hands thoroughly with soap and water when finished.

1258

Section  XIII  Infectious Diseases

Since humans are not commonly infected with T. gondii from contact with individual cats, testing healthy cats for toxoplasmosis is not recommended (Brown et al., 2003). Fecal examination is an adequate procedure to determine when cats are actively shedding oocysts but cannot predict when a cat has shed oocysts in the past. There is no serologic assay that accurately predicts when a cat shed T. gondii oocysts in the past, and most cats that are shedding oocysts are seronegative. Most seropositive cats have completed the oocyst shedding period and are unlikely to repeat shedding; most seronegative cats would shed the organism if infected. If owners are concerned that they may have acquired toxoplasmosis, they should see their doctor for testing. Common sense practices should also be followed (Box 274-1).

References and Suggested Reading Barrs VR, Martin P, Beatty JA: Antemortem diagnosis and treatment of toxoplasmosis in two cats on cyclosporine therapy, Aust Vet J 84:30, 2006.

C hapter  

Bernstein L et al: Acute toxoplasmosis following renal transplantation in three cats and a dog, J Am Vet Med Assoc 215:1123, 1999. Brown RR et al: Feline zoonoses guidelines from the American Association of Feline Practitioners, Compend Contin Educ Pract Vet 25:936, 2003. Dubey JP, Lappin MR: Toxoplasmosis and neosporosis. In Greene CE, editor: Infectious diseases of the dog and cat, ed 3, St Louis, 2006, Saunders, 2006, p 754. Flegr J: Effects of Toxoplasma on human behavior, Schizophr Bull 2007. Kaplan JE, Massur H, Holmes KK: Guidelines for preventing opportunistic infections among HIV-infected persons, MMWR 51(RR08):1, 2002. Last RD et al: A case of fatal systemic toxoplasmosis in a cat being treated with cyclosporine A for feline atopy 15:194, 2004. Lindsay DS, Blagburn DL, Dubey JP: Feline toxoplasmosis and the importance of the Toxoplasma gondii oocyst, Compend Contin Educ Pract Vet 19:448, 1997. Vollaire MR, Radecki SV, Lappin MR: Seroprevalence of Toxoplasma gondii antibodies in clinically ill cats of the United States, Am J Vet Res 66:874, 2005. Webster JP: The effect of Toxoplasma gondii on animal behavior: playing cat and mouse, Schizophr Bull 2007.

275

Pneumocystosis Remo Lobetti, Bryanston, South Africa

P

neumocystis carinii is a saprophyte of low virulence that primarily occurs in the mammalian lung. Clinical pneumonia has been reported to occur spontaneously in dogs associated with a suspected immunodeficiency. Airborne transmission is suspected because healthy animals become infected when they are housed with infected animals. It is presumed that the organism may have a dormant life stage in the environment. The taxonomy of P. carinii is uncertain. It has been classified as a unicellular protozoan belonging to the phylum Sarcomastigophora, subphylum Sarcodina. However, its reproductive behavior is similar to that of yeast cells. On the other hand, phylogenetic classification based on 16S-like ribosomal ribonucleic acid sequences indicates that P. carinii is most closely related to fungi of the class Ascomycetes, yet it behaves like a protozoan because it is sensitive to drugs used to treat protozoan infections.

The morphology of P. carinii and the histopathology of the lesions produced by both human and animal isolates throughout the world are similar. Only a single species name has been assigned to the genus Pneumocystis, but antigenic differences suggest that several strains may exist. Although currently controversial, four species have been described: two species that infect dogs and rats, P. carinii and Pneumocystis wakefieldiae; one species, Pneumocystis murina, which infects mice; and Pneumocystis jirvecii, which infects humans. Biologic differences among isolates from different hosts are suggested by the relative difficulty of experimental interspecies transmission.

Epidemiology P. carinii appears to be maintained in nature by transmission from infected to susceptible animals within a species. The primary mode of spread is thought to be airborne

droplet transmission between hosts. The contagious nature of pneumocystosis is suggested by the epidemic spread that has occurred in institutionalized humans. Sporadic case reports may represent an activation of latent infection by stress, crowding, and immunosuppressive therapy during hospitalization of latent carriers. Clinical disease also has been experimentally activated after cortisone therapy, cytotoxic chemotherapy, and irradiation. A higher prevalence of infection has been found in dogs with canine distemper compared with a corresponding control population. The entire life cycle of P. carinii is completed within the alveolar spaces, where organisms adhere in clusters to the pneumocytes. Two main forms, the trophozoite and cyst, are found. Although Pneumocystis infections are usually limited to the lung, in humans and in a single dog organisms have been reported in extrapulmonary sites. Severe immunodeficiency states in humans such as acquired immune deficiency syndrome (AIDS) can be associated with lymphatic or hematogenous dissemination of the organisms from the lungs to other tissues. Transmission of infection to an offspring may occur via aspiration of amniotic fluid contaminated by placental infection.

Pathogenesis Pneumocystis can be inhaled from the environment and can colonize the lower respiratory tract of clinically healthy mammals; however, organisms rarely multiply to large numbers in the lungs of clinically healthy hosts. In conditions in which there is impaired host resistance or preexisting pulmonary disease, proliferation of organisms can occur. Alveolocapillary blockage and decreased gaseous exchange result secondary to the overgrowth and clustering of P. carinii within the alveolar spaces. Intraalveolar organisms are often accompanied by thickening of alveolar septa, but organisms seldom invade the pulmonary parenchyma and are rarely found in alveolar macrophages. The inflammatory response that the organism provokes contributes to the pulmonary alveolar ­damage and clinical pathophysiology.

Clinical Findings Most reported canine cases have been in miniature dachshunds younger than 1 year, although cases of pneumocystosis have been reported in a Shetland sheepdog, a Yorkshire terrier, and cavalier King Charles spaniels. The syndrome of common variable immunodeficiency, in which there is absence of B cells resulting in little or no antibody production in association with defective T cells, appears to occur in affected miniature dachshunds and is likely a risk factor for clinical disease in these dogs. The typical clinical history in dogs with pneumocystosis is that of gradual weight loss and variable polypnea progressing over a period of time. Weight loss, which occurs in spite of a good appetite in most dogs, may be associated with diarrhea and occasional vomiting. Coughing is not always present, but exercise intolerance is present consistently. Infected animals may show some response to antibiotic or cortisone therapy.

Chapter  275  Pneumocystosis

1259

Affected dogs generally remain relatively alert and afebrile. Abnormalities on clinical examination include polypnea, tachycardia, and pulmonary crackles on thoracic auscultation. Animals are usually in poor condition, cachectic, and often show dermatologic changes such as superficial bacterial pyoderma and demodicosis. Although the mucous membranes generally are of normal color, in severely affected animals they may be cyanotic.

Diagnosis Hematologic abnormalities are usually nonspecific, with neutrophilic leukocytosis and left shift seen most consistently; eosinophilia and monocytosis occur less frequently. The white cell response often appears inadequate in light of the pulmonary changes. Polycythemia may occur secondary to arterial hypoxemia from impaired gaseous exchange. Thrombocytosis is often also present. Serum proteins are usually normal with a low-to–low normal globulin level, which correlates with low γ-globulin levels on serum protein electrophoresis. Decreased lymphocyte function and low levels of serum immunoglobulin (Ig)A, IgG, and IgM have been reported. Arterial hypoxemia, hypocapnia, and alkalemia indicate an uncompensated respiratory alkalosis. The PaO2 is often lower than would be expected from the clinical signs and thoracic radiographs. Findings on survey thoracic radiography include diffuse, bilaterally symmetric, alveolar-to-interstitial lung disease. Solitary lesions, unilateral involvement, cavitary lesions, spontaneous pneumothorax, or lobar infiltrate occasionally may be present. Tracheal elevation, rightsided heart enlargement, and pulmonary arterial enlargement reflect cor pulmonale secondary to the chronic pulmonary disease. The diagnosis of pneumocystosis requires direct demonstration of P. carinii in either lung biopsy specimens or respiratory fluids. Transtracheal or endotracheal washings and oropharyngeal secretions may contain organisms, with transtracheal aspirates being very effective in identifying organisms in dogs. Samples for cytology may be obtained by endobronchial brushing and transbronchoscopic biopsy, but these procedures require special endoscopic equipment and involve the risks of general anesthesia. Transtracheal or endotracheal lavage and percutaneous transthoracic needle aspiration are more available to practitioners and have been shown to have a good correlation with transbronchoscopic biopsy findings in confirming a diagnosis. None of the cytologic techniques are as reliable or as definitive as lung biopsy for documenting active pneumocystosis. Unfortunately lung biopsy has the greatest risk of complications such as hemorrhage, secondary infection, pneumothorax, and death from anesthesia. Antimicrobial therapy can begin 24 to 48 hours before specimen collection in a patient suspected of having pneumocystosis without hindering the identification of organisms in the sample. Diff-Quik (a modified Giemsa stain) can be used as a fast and inexpensive screening stain after which negative results can be confirmed with more sensitive staining such as methenamine silver for cysts or with Giemsa for nuclei of intracystic sporozoites and trophozoites.

1260

Section  XIII  Infectious Diseases

Other diagnostic tests that have been used include direct or indirect fluorescent antibody test for detecting organisms in tracheal aspirates and immunoperoxidase stains for impression smears and formalin-fixed, paraffin-embedded lung sections. The polymerase chain reaction has been effective in the detection of organisms in bronchoalveolar lavage specimens from humans and lung tissue from dogs. In humans serologic tests have been developed; however, their diagnostic value is uncertain since antigenemia is found in up to 15% of clinically normal humans.

Therapy Specific therapy is most beneficial in cases in which the disease has been diagnosed during the early stages. Although a number of drugs have been used in the treatment of P. carinii, the two drugs that have been used successfully to treat pneumocystosis are pentamidine isethionate and the combination of trimethoprim and sulfamethoxazole, the latter being the most effective in the dog. Pentamidine isethionate is an aromatic diamidine used in humans. Its major side effects include impaired renal function, hepatic dysfunction, hypoglycemia, hypotension, hypocalcemia, urticaria, and hematologic disorders. Intramuscular administration of this drug has been successful in treating a dog with pneumocystosis, with the only side effect being localized pain at the injection site. Pentamidine has also been used at a reduced dosage in combination with sulfonamides to lower its toxic side effects. Other aromatic diamidines such as diminazene, imidocarb, and amicarbalide have been more effective than pentamidine in treating experimental P. carinii pneumonia. The combination of trimethoprim and sulfamethoxazole has been found to be more effective and less toxic than pentamidine in treating and preventing Pneumocystis pneumonia in immunosuppressed humans. A dosage of 15 mg/kg TID or 30 mg/kg BID for 3 weeks has been used successfully in miniature dachshunds with pneumocystosis. Folic acid supplementation should be given if side effects such as leukopenia and anemia are observed or if long-term therapy is required. Atovaquone is another drug licensed for the treatment of humans with pneumocystosis. It is not as effective as pentamidine or trimethoprim-sulfamethoxazole but has a reported lower toxicity. Bioavailability is increased when the drug is given with food with a high fat content. Combination therapy using clindamycin and primaquine has also been effective both in vivo and in vitro, but neither drug is effective alone. Dapsone and trimethoprim or pyrimethamine in combination have been effective in experimental animals and clinical trials in immunosuppressed humans with pneumocystosis. Trimetrexate, a lipid-soluble antifolate, has been given concomitantly with leucovorin to humans with Pneumocystis pneumonia and AIDS. As with most of the other drugs, neutropenia with or without thrombocytopenia has been the main

side effect. In experimentally infected animals P. carinii is resistant to imidazole antifungal drugs, but the anthelmintics benzimidazole and albendazole have been shown to have some effect. Supportive care is essential for any patient with ­pneumocystosis. Oxygen therapy administered by cage, mask, or intubation is needed (Chapter 137); and ­ventilatory assistance may also be required (Chapter 138). Bronchodilators may help reduce airway resistance. If a patient is receiving immunosuppressive agents, they should be discontinued temporarily; however, antiinflammatory drugs may be indicated. In humans the successful treatment of pneumocystosis results in additional pulmonary dysfunction and a decline in arterial oxygen related to the inflammatory reaction to dying organisms, and the administration of antiinflammatory doses of cortisone has been shown to improve pulmonary function and survival. Nonspecific immunostimulants such as cimetidine and levamisole have been given adjunctively to treat affected miniature dachshunds, but in all probability they have limited effect. Once a diagnosis of pneumocystosis is made, it is very important that a predisposing immune deficiency state be investigated. In humans prophylactic treatment with trimethoprim-sulfamethoxazole drugs has been used in hospitalized patients who are receiving irradiation or immunosuppressive agents or who have immunodeficiencies and debilitating diseases. Similar precautions are deemed not warranted for pets because pneumocystosis has not been recognized with similar frequency in such instances.

References and Suggested Reading Beard CB et al: Genetic variation in Pneumocystis carinii isolates from different geographic regions: implications for transmission, Emerg Infect Dis 6:265, 2000. Cabanes FJ et al: Pneumocystis carinii pneumonia in a Yorkshire terrier dog, Med Mycol 38:451, 2000. Greene CE, Chandler F, Lobetti RG: Pneumocystosis. In Greene CE, editor: Infectious diseases of the dog and cat, ed 3, St Louis, 2005, Saunders, p 651. Kirberger RM, Lobetti RG: Radiographic aspects of Pneumocystis carinii pneumonia in the miniature dachshund, Vet Radiol Ultrasound 39:313, 1998. Kovacs JA et al: New insights into transmission, diagnosis, and drug treatment of Pneumocystis carinii pneumonia, J Am Med Assoc 286:2450, 2001. Lobetti R: Common variable immunodeficiency in miniature dachshunds affected with Pneumocystis carinii pneumonia, J Vet Diagn Invest 12:39, 2000. Lobetti R: Pneumocystis carinii infection in miniature dachshunds, Compend Contin Educ Pract Vet 23:320, 2001. Watson PJ et al: Immunoglobulin deficiency in cavalier King Charles spaniels with Pneumocystis pneumonia, J Vet Intern Med 20:523, 2006. Sukura A, Saari S, Jarvinen A: Pneumocystis carinii pneumonia in dogs: a diagnostic challenge, J Vet Diagn Invest 8:124, 1996.

C hapter 

276

Feline Cytauxzoonosis J. Paul Woods, Guelph, Ontario, Canada

C

ytauxzoon felis is an emerging tick-transmitted intracellular protozoon in wild and domestic cats. In domestic cats this microorganism causes severe disease characterized by hemolytic anemia and circulatory impairment with high mortality. The genus Cytauxzoon belongs to the subphylum Apicomplexa, order Piroplasmidae, family Theileriidae, which are parasites of mammals. Cytauxzoon exist in two distinct tissue forms: an erythrocyte phase (piroplasm) (Fig. 276-1) and a tissue phase (schizont) (Fig. 276-2). The genus Cytauxzoon was designated for species reported initially in African ungulates in which the tissue phase develops in mononuclear phagocytes lining the blood vessels of numerous organs, whereas the genus Theileria invades lymphocytes during the schizogenous phase. Cytauxzoon are closely related to the genus Babesia; however, Babesia spp. have an erythrocyte stage exclusively without a tissue phase.

Epidemiology C. felis was first recognized in 1976 in Missouri. It has now been reported in the south central, southeastern, mid-Atlantic, and Gulf coast states of the United States. The pattern of geographic distribution is probably affected by the availability of both reservoir hosts (wild bobcats) and arthropod vectors (Dermacentor variabilis). The natural life cycle of C. felis is not completely understood. The cat was presumed to be an accidental terminal host with a predominant rapidly fatal disease, but recent findings of asymptomatic infected cats have led to the possibility of cats serving as an additional reservoir for C. felis. In contrast, bobcats (Lynx rufus) are the presumed reservoir hosts, acting as persistent carriers of the organism and usually developing only mild or subclinical infection. However, there is a paucity of information on blood parasites of free-ranging cats, and Cytauxzoon has only been reported in bobcats since 1982; thus questions remain as to whether this is a new disease of felids or only a newly identified disease. Mountain lions (Felis concolor) from Florida and Texas also have been reported to carry the organism. There has been a correlation of disease with tick interchange among wild and domestic felids, with ticks presumably transmitting the organism between cats by feeding. The only tick demonstrated experimentally to be a competent vector for Cytauxzoon is D. variabilis (American dog tick). Transtadial transmission occurs in ticks, but transovarial transmission has not been demonstrated. However, cytauxzoonosis may be more widespread than previously recognized

because cytauxzoonosis-like diseases have been reported in domestic cats in Zimbabwe and Spain, in Pallas’ cats (Otocolobus manul) from Mongolia, and in a lion (Panthera leo) in Brazil. Experimental studies have revealed no zoonotic or agricultural risk for C. felis. Feline cytauxzoonosis is highly seasonal, occurring in spring to early fall, with the highest incidence in early spring to early summer, which correlates with tick activity. Outdoor cats with access to wooded environments are at greatest risk of infection, presumably because of increased exposure to tick vectors. Within endemic areas there is a large variability in incidence of disease between relatively short distances. In fact, there are hyperendemic foci as suggested by detection of infection in more than one cat in multicat households, a phenomenon likely the result of common exposure to tick populations rather than direct cat-to-cat transmission. Cytauxzoonosis has been most commonly reported in middle-aged cats, but it can occur in cats of any age, with no sex or breed predilections. A recent report suggested young male cats to be at higher risk. A recent study screening for C. felis in feral cats in the southeastern United States reported a prevalence of 0.3% with an estimated prevalence range of 0% to 0.8%.

10m

Fig. 276-1  Peripheral blood from a cat with cytauxzoonosis. Four piroplasms are present within erythrocytes. Two of the piroplasms (top) each contain two nuclear areas. Two of the erythrocytes (bottom) contain small particulate stain precipitate that must be differentiated from organisms (Wright-Giemsa stain). (From Meinkoth J, Kocan AA: Feline cytauxzoonosis, Vet Clin Small Anim 35:89, 2005, with permission.) 1261

Section  XIII  Infectious Diseases

1262

50m

A

20m

B Fig. 276-2  A, Impression smear of spleen from a cat with

cytauxzoonosis. Five large schizon-containing macrophages are present. Scattered myeloid cells and plasma cells are also present. B, Higher magnification of the area shown in A. The nucleus of a host cell is outlined by arrowheads. The host cell nucleus contains a greatly enlarged nucleolus. The schizont completely fills the cells’ cytoplasm, often being indistinct. In portions of the cells multiple merozoites are seen forming within the schizont, giving the cytoplasm a “packeted” appearance (arrow) (WrightGiemsa stain). (From Meinkoth J, Kocan AA: Feline cytauxzoonosis, Vet Clin Small Anim 35:89, 2005, with permission.)

Pathogenesis The limited information available from investigations of C. felis reveals a complex pathogenesis. Experimental studies demonstrate that the clinical disease in domestic cats depends on exposure to the schizogenous tissue phase of C. felis. Inoculation with schizont homogenate induces disease, whereas inoculation with only erythrocyte-phase piroplasms results in only erythroparasitemia without schizont development or clinical signs of disease. Cats exposed to infected D. variabilis develop both schizogenous phases and erythroparasitemia and become ill with cytauxzoonosis. Piroplasms cannot progress through their natural life cycle without passing through the tick host. Thus the ticks are not just mechanical vectors but are also necessary to complete the C. felis life cycle. In ticks, transtadial but not transovarial transmission has been demonstrated. Oral and contact exposure does not result in disease; therefore close contact between cats without tick vectors does not pose a risk for disease transmission.

After infection the organism undergoes schizogony, an asexual reproductive phase, in mononuclear phagocytic cells associated with vessels of almost every organ. As the schizonts (see Fig. 276-2) undergo schizogony and binary fission, macrophages lining the blood vessels enlarge tremendously and occlude venules in liver, spleen, lung, and lymph nodes, resulting in a thrombus-like mechanical obstruction of blood flow and tissue hypoxia. The schizont is associated with clinical disease; the greater the schizont burden, the more severe the clinical illness. Domestic cats have extensive schizont burdens, whereas mildly affected bobcats have a limited and transient schizogenous phase. The tissue phase is also suspected to release toxic, pyrogenic, and vasoactive products that contribute to clinical manifestations. The schizogenous tissue phase, detectable by 12 days after infection, is responsible for the venous congestion, thrombotic disease, and organ failure that lead to death in most cats within 3 weeks of infection. Schizonts develop merozoites that are released when infected macrophages rupture. Merozoites undergo endocytosis by erythrocytes, giving rise to late-stage erythroparasitemia, recognized as piroplasms (see Fig. 276-1) as the disease progresses. Although graphic, the piroplasm itself is relatively innocuous; however, it may induce erythrocyte destruction and erythrophagocytosis. Cats exposed to just piroplasms remain parasitemic (piroplasms may decrease to a low level) but do not develop protective immunity. In experimental studies of infection a few cats (≈4 out of >500 cats) did survive infection from exposure to schizonts. In contrast to the piroplasm-exposed cats, these cats developed protective immunity.

Clinical Manifestations Cytauxzoonosis follows an acute course, with the stage of disease determining the presenting clinical signs. In natural infections the prepatent period is between 2 to 3 weeks, with the onset of clinical disease occurring 1 to 3 weeks after infection. The clinical signs are initially nonspecific, consisting of depression, dehydration, and anorexia followed by fever (as high as 40 to 41.6 ° C [107 ° F]), icterus, anemia, dark urine, tachycardia, splenomegaly, variable hepatomegaly, reluctance to move, and vocalizing with generalized pain. In late stages the cats are terminally moribund and dyspneic, and after fever peaks the body temperature may subside to normal or frequently become subnormal (24 to 48 hours before death). Miscellaneous neurologic signs observed in some cats have included ataxia, nystagmus, seizures, tetany, aggression, and coma. Typically the course of disease is rapid, and cats usually die within 7 days after the onset of clinical signs. However, some cats survive infection and may remain asymptomatic carriers for months to years.

Laboratory and Pathologic Findings In cats infected with cytauxzoonosis a complete blood count may reveal any combination of cytopenias. Anemia, probably caused by erythrophagocytosis and characterized as normocytic, normochromic, and nonregenerative, is

common. In contrast to anemia associated with infection from other hemoparasites, the absence of regenerative responses may be because the acute course of the disease gives insufficient time for a regenerative response or because of bone marrow suppression from inflammatory disease. Leukopenia consisting of neutropenia with toxic changes is common. Thrombocytopenia may result from increased consumption. Activated partial thromboplastin time and partial thromboplastin time have been prolonged in some cats. Red blood cells (RBCs) stained with Wright, Giemsa, or other Romanovsky stains may demonstrate piroplasms (see Fig. 276-1), the erythrocytic phase of C. felis. The piroplasms consist of a dark purple, eccentric nucleus within a pale light blue or nearly colorless cytoplasm. There are usually one to two organisms per RBC, but there can be as many as four. The piroplasms are pleomorphic, classically appearing as 1- to 2-μm–diameter “signet ring” (round to oval with a single peripherally located nucleus). They can also be elongated with a bipolar nucleus (“safety pin”), commashaped, linear, or tetrad (“Maltese cross”). The piroplasms are located intracellularly, in contrast to the epicellular location of Mycoplasma hemofelis. Piroplasms appear late in the course of disease and may be absent or in very low numbers on initial examination in up to 50% of cases. The proportion of affected RBCs with observable piroplasms is generally low (6 years). Unfortunately investigations of the survivor cats have not elucidated if survival was caused by therapeutic management, the survivor cats’ innate immunity, detection of previously unrecognized carriers, atypical route of infection (e.g., bite wound) resulting in asymptomatic parasitemia, or a less virulent form of C. felis. Although no definitive antiprotozoal therapy has been proven consistently effective, cats present in severe distress, requiring immediate aggressive supportive therapy. The goal of therapy is to sustain the cat to gain time for its innate defenses to battle the infection and/or for investigational antiprotozoal therapy. Depending on the cat’s condition, treatment can involve intravenous fluid therapy to rehydrate and correct metabolic imbalances, prophylactic antibiotics for secondary bacterial infection, heparin (100 to 150 U/kg subcutaneously [SQ] q8h) to minimize thrombus formation and development of disseminated intravascular coagulation, and blood products as needed for anemia.

1264

Section  XIII  Infectious Diseases

Administration of definitive antiprotozoal treatments to infected cats is controversial because of drug toxicity, the lack of availability and approval, and mostly the paucity of evidence supporting clinical efficacy. Therapies that have been unsuccessful include parvaquone, buparvaquone, sodium thiacetarsemide, and tetracycline. Therapies that have reported inconsistent success are imidocarb dipropionate (Imizol, Schering Plough Animal Health) at a dosage of 2 to 4 mg/kg every 7 days intramuscularly pretreated with glycopyrrolate (0.005 to 0.01 mg/kg intramuscularly [IM] or SQ); atovaquone (Mepron, GlaxoSmithKline) at a dosage of 15 mg/kg every 8 hours orally for 10 days combined with azithromycin (Zithromax, Pfizer) at a dosage of 10 mg/kg every 24 hours orally for 10 days. Although unavailable in North America, another therapy is diminazene aceturate (Berenil, Intervet) at a dosage of 2 mg/kg every 7 days intramuscularly. Although at present a vaccine is not available, one of the surviving experimental cats was resistant to subsequent challenge with lethal doses of C. felis, suggesting that it may be possible to vaccinate cats against C. felis. Until better therapy is developed, prevention of infection is paramount. Transmission cannot occur directly from cat to cat; therefore prevention involves minimizing chances of infection from the tick vector by indoor confinement during tick season, avoidance of rural wooded areas, and ectoparasite control (e.g., pyrethrins, fipronil). It is unknown how long a tick must be attached to transmit the disease. Feline blood donors should be screened and free of ectoparasites (ideally kept indoors). Transfusions from recovered cats do not result in illness even if piroplasm-containing erythrocytes are transfused; however, recently infected cats can transmit

schizont-containing circulating monocytes, which can cause disease. Despite its geographic restrictions, feline cytauxzoonosis is more widespread then previously reported. Recently cases have been recognized in new regions and with increased frequency in previous endemic areas. This change could be the result of changes in distribution, prevalence, or transmission of infected ticks or infected reservoir animals. Concomitantly there has been an increase in recognition and diagnosis by veterinarians. Because of the potential dangers of spread by importation, veterinarians outside endemic areas need to be cognizant of feline cytauxzoonosis and aware of the potential concern for domestic and exotic cats in areas with appropriate reservoirs and tick vectors.

Suggested Reading Birkenheuer AJ et al: Development and evaluation of a PCR assay for the detection of Cytauxzoon felis DNA in feline blood samples, Vet Parasitol 137:144, 2006. Bondy PJ, Cohn LA, Kerl ME: Feline cytauxzoonosis, Compend Contin Educ Pract Vet 27:69, 2005. Greene CE et al: Administration of diminazene aceturate or imidocarb dipropionate for treatment of cytauxzoonosis in cats, J Am Vet Med Assoc 215:497, 1999. Haber MD et al: The detection of Cytauxzoon felis in apparently healthy free-roaming cats in the USA, Vet Parasitol 146:316, 2007. Meinkoth J et al: Cats surviving natural infection with Cytauxzoon felis: 18 cases (1997–1998), J Vet Intern Med 14:521, 2000. Meinkoth J, Kocan AA: Feline cytauxzoonosis, Vet Clin Small Anim 35:89, 2005.

C hapter 

277

Systemic Fungal Infections Rance K. Sellon, Pullman, Washington AlFRED M. legendre, Knoxville, Tennessee

T

he systemic fungal infections are a collection of well-known and well-described conditions causing clinical signs of multisystemic disease. Most discussions of systemic fungal infections focus on four organisms: Blastomyces dermatitidis, Coccidioides immitis, Histoplasma capsulatum, and Cryptococcus neoformans. Most of the information about the pathology and pathophysiology of these infections has been well described in other texts and will not be repeated. This chapter summarizes important findings about the epidemiology of infection, spectrum of clinical disease, and diagnostic developments published in the recent veterinary medical literature. Finally, therapeutic approaches are described for the common systemic mycotic infections.

areas. Understanding the widening geographic distributions that have emerged in humans could also serve as a sentinel warning for veterinarians in such areas. Additional studies have explored the risk factors for canine infection with C. immitis. Dogs that spent a lot of time outdoors, that roamed over a large surface area, and that spent time walking across the desert had a greater risk of C. immitis infection than mainly indoor dogs or dogs that walked on sidewalks. (Butkiewicz et al., 2005). Many dogs in an endemic area become infected with C. immitis (as determined by development of C. immitis antibodies), but few actually develop clinical disease.

Epidemiology

The spectrum of clinical disease caused by the systemic fungal organisms is well known to clinicians that practice in endemic areas; each of the organisms has a predilection for certain organ systems, and the disease typically reflects affected organs. Common to most of the systemic fungal organisms are respiratory disease, bone infection, central nervous system infection (including eyes), lymph node involvement, and skin lesions (Table 277-2). An additional presentation for coccidioidomycosis is pericardial effusion. In 17 dogs with C. immitis– induced pericardial disease, affected dogs had clinical signs typical of pericardial disease and right heart failure: abdominal effusion, muffled heart sounds, poor pulse quality, tachypnea, and jugular pulses (Heinritz, et al., 2005). Cardiac ultrasound examinations documented the presence of pericardial effusion and thickened pericardium in most of the dogs. Subtotal pericardectomy was associated with resolution of clinical signs of right heart failure but was also associated with high (23.5%) perioperative mortality; however, the exact cause of death was established in few of the dogs. There was pyogranulomatous pericarditis in all dogs, and there were C. immitis spherules in a majority of dogs. In addition to surgical treatment, dogs with pericardial coccidioidomycosis were also treated with antifungal drugs. Cardiovascular disease is uncommon in dogs with blastomycosis, but there was a report of eight dogs with cardiovascular blastomycosis (Schmiedt, et al., 2006). Affected dogs had clinical signs typical of blastomycosis, including fever and signs of respiratory disease that reflected fungal pneumonia (lethargy, cough, dyspnea). Some dogs had syncope and cardiac arrhythmias, including atrioventricular blocks. Most had echocardiographic abnormalities that varied from mass-like lesions to evidence of pulmonary hypertension and associated right-sided ­cardiomegaly.

In the United States the principal endemic areas of infection for each of the systemic fungal organisms remain constant (Table 277-1). However, some systemic fungal infections have occurred in patients living in areas outside the typical foci of endemic fungal infection. In one report two cats that had not traveled outside of California had confirmed histoplasmosis. The cats lived in an area where there had been recent soil disruption. Interestingly, both of the cats in this report were noted to be completely indoor cats. An outbreak of cryptococcosis on Vancouver Island, BC, Canada saw a spike in disease of both humans and animals (Kidd et al., 2004). In contrast to infection with C. neoformans, affected patients were infected with Cryptococcus gattii, a species of Cryptococcus more prevalent in Australia. Blastomycosis has been documented recently in humans living in Colorado who were working with prairie dogs, potentially extending the distribution of this organism westward. Although animals that go outdoors are at the greatest risk of exposure to infection, animals that are exclusively indoors have also contracted systemic fungal infections. In addition to the cats with acquired histoplasmosis, ­blastomycosis has been documented in strictly indoor cats. In humans acquisition of systemic fungal infection (histoplasmosis) has been linked to air-handling systems that channel infectious organisms into buildings (Luby et al., 2005) and a similar means may operate to cause infection in indoor animals. As with the California cats, disruption of soil or ground surface has been associated with infection in humans in nearby buildings. The clinician’s assessment of risk of infection/exposure should consider the possibility of infection in nontraditional

Clinical Disease

1265

1266

Section  XIII  Infectious Diseases

Table  277-1 Usual Geographic Distribution of the Systemic Fungal Infections Organism

Geographic Distribution

Coccidioides immitis

Southwestern United States, ­especially California and Arizona; Mexico; Central America; South America United States primarily east of the Mississippi river; Central America; South America Ohio, Missouri and Mississippi river drainages; mid-Atlantic states (Georgia, South Carolina, North Carolina, Virginia, Maryland); Canada (Ontario, Manitoba, Quebec) Worldwide Tropical and subtropical regions worldwide; Vancouver Island and Vancouver, British Columbia, Canada

Histoplasma capsulatum

Blastomyces dermatitidis

Cryptococcus neoformans Cryptococcus gattii

Necropsy lesions included myocardial blastomycosis, ­blastomycosis-induced epicarditis or pericarditis, infection of the adventitia of the aorta, and inflammation and fibrosis of the atrioventricular nodal region. Typical blastomycosis lesions were found in other organs. Although the authors speculated that cardiac involvement in dogs with blastomycosis is likely more widespread than recognized in this retrospective study, it still appears to be uncommon. Nevertheless, blastomycosis should be suspected in dogs with clinical signs of myocardial or conduction system disease. Blastomycosis is an uncommon disease in cats compared to dogs, but the spectrum of clinical disease in eight cats with blastomycosis resembled the disease in dogs (Gilor, et al., 2006). Fever, lethargy, anorexia, and

Table  277-2 Systems Commonly Affected in Patients With Systemic Fungal Infections* Organism

Organ Systems

Coccidioides immitis

Respiratory tract, skeleton, skin, pericardium Respiratory tract, liver, spleen, gastrointestinal tract (dog), skeleton, eyes Respiratory tract, bone, lymph nodes, eyes, brain, skin/ subcutaneous tissue, external nares Nasal cavity, skin, eyes, central nervous system, lymph nodes

Histoplasma capsulatum

Blastomyces dermatitidis

Cryptococcus ­neoformans; C. gattii

*In any given patient, dissemination to other organs is possible.

weight loss were common clinical complaints. Cats with blastomycosis had skin and respiratory tract disease (dyspnea, tachypnea, cough). Skin lesions were primarily nonulcerated dermal masses; in contrast to cutaneous blastomycosis in dogs, in which draining lesions are common, the cutaneous lesions in these cats were not draining. Peripheral lymph node enlargement was not seen in any of the cats. Chorioretinitis and central nervous system disease were also observed. Results of complete blood count and serum biochemical profile were nonspecific in the cats of the study. Thoracic radiographs of affected cats demonstrated nodular interstitial-to-alveolar patterns and consolidation. Involvement of the right cranial lung lobe was common, and diffuse bronchial patterns were also frequently observed. As is true with dogs, antemortem diagnosis of blastomycosis in the cats of this study was accomplished by cytologic identification of organisms obtained from aspirates/ imprints (skin, lungs, spleen) or lavage of the ­respiratory tract.

Diagnosis The definitive diagnosis of all of the systemic fungal infections is established by demonstration of organisms in samples obtained for cytologic or histopathologic examination. With the exception of cryptococcosis, for which serologic assays detect capsular antigen, diagnosis of the other fungal infections based on serologic assays has remained problematic, typically because of low sensitivity and/or specificity of assays that detect antibody. Radioimmunoassays that detect antibody to the WI-1 antigen, the major surface protein of B. dermatitidis, have proven more sensitive and specific than assays that detect antibody to B. dermatitidis antigen A. However, the radioimmunoassay is not yet available commercially. Other developments in the diagnosis of the systemic fungal infections by serologic assays in humans have seen initial translation to veterinary medicine. Diagnosis of canine blastomycosis by detection of specific antigen in serum or urine is promising (Spector et al., 2006). The urine antigen assay is more sensitive than the serum assay. The sensitivity and specificity of the urine assay was 93% and 98%, respectively, when evaluating known positive and negative samples. The assay may also have application in determining duration of treatment, but further studies are needed. Additional information on this assay can be found at www.miravistalabs.com. There is crossreactivity between the Histoplasma and Blastomyces organisms. There is also an antigen assay for histoplasmosis, but no studies have been published yet on its application in dogs and cats. These antigen assays are currently available. The work by Shubitz and associates (2005) indicated that, because of overlap in titers between subclinically and clinically infected dogs, serologic titers alone are ­insufficient to establish a definitive diagnosis of coccidioidomycosis. Thus the diagnosis of this infection requires that additional supportive information (physical ­examination abnormalities, laboratory abnormalities, radiographic imaging, cytology, and histology) be obtained to establish a clinical diagnosis.

Chapter  277  Systemic Fungal Infections



1267

Table  277-3 Therapeutic Suggestions for the Systemic Fungal Infections* Organism

Treatment Recommendations†‡

Coccidioides immitis Histoplasma capsulatum

Ketoconazole§ 10 mg/kg PO q12h or fluconazole 10 mg/kg PO q12h Itraconazole§ 5-10 mg/kg PO q12-24h Amphotericin B 0.5 mg/kg IV q48h for gastrointestinal infection Blastomyces dermatitidis Dogs: itraconazole 5 mg/kg PO q24h Cats: itraconazole 10 mg/kg PO daily Cryptococcus neoformans; Cat: itraconazole 50-100 mg/cat daily; terbinafine 10 mg/kg/day for cats that develop resistance to azoles C. gattii Dog: optimal therapy not established, but itraconazole 10 mg/kg/day or amphotericin B 1 mg/kg intravenously three times weekly is suggested

*Initial suggestions only; for more comprehensive treatment information, consult Bonagura JD, editor: Kirk’s current veterinary therapy XIII (small animal practice), ed XIII, Philadelphia, 2000; or relevant chapters in Greene CE, editor: Infectious diseases of the dog and cat, ed 3, Philadelphia, 2006, Saunders Elsevier. † If unfamiliar with drugs or their administration, please consult a veterinary formulary or other suggested readings. ‡ Duration of therapy for most is a minimum of 60 to 90 days, or at least 30 days beyond resolution of all clinical signs. C. immitis infections may require longer treatment periods. § Give with food to increase absorption.

Treatment A number of newer antifungal drugs have been developed and proven efficacious in the treatment of the systemic fungal infections in humans. Many belong to the azole class of drugs that includes itraconazole and ketoconazole. Some of the newer azoles used in humans include voriconazole, posaconazole, and ravuconazole. Although such drugs have proven to be of benefit in humans with fungal infections refractory to therapy with the older azoles such as itraconazole, ketoconazole, and fluconazole, there are no published investigations in small animal patients. A common feature of these drugs is the high cost for these agents. Currently accepted recommendations for the treatment of the various systemic fungal infections are summarized in Table 277-3.

References and Suggested Reading Butkiewicz CD, Shubitz LF, Dial SM: Risk factors associated with Coccidioides infection in dogs, J Am Vet Med Assoc 226:1851, 2005.

Gilor C et al: Clinical aspects of natural infection with Blastomyces dermatitidis in cats: 8 cases (1991-2005), J Am Vet Med Assoc 229(1):96, 2006. Heinritz CK et al: Subtotal pericardectomy and epicardial excision for treatment of coccidioidomycosis-induced effusiveconstrictive pericarditis in dogs: 17 cases (1999-2003), J Am Vet Med Assoc 227:435, 2005. Kidd SE et al: A rare genotype of Cryptococcus gattii caused the cryptococcosis outbreak on Vancouver Island (British Columbia, Canada), Proc Natl Acad Sci USA 101(49):17258, 2004. Luby JP et al: Recurrent exposure to Histoplasma capsulatum in modern air-conditioned buildings, Clin Infect Dis 41:170, 2005. Schmiedt C et al: Cardiovascular involvement in 8 dogs with Blastomyces dermatitidis infection, J Vet Intern Med 20:1351, 2006. Shubitz LF et al: Incidence of Coccidioides infection among dogs residing in a region in which the organism is endemic, J Am Vet Med Assoc 226:1846, 2005. Spector D et al: Antigen testing for the diagnosis of blastomycosis, J Vet Intern Med 20:711, 2006.

C hapter  

278

Pythiosis and Lagenidiosis Amy M. Grooters, Baton Rouge, Louisiana

P

 ythium insidiosum and Lagenidium spp., the causative agents of pythiosis and lagenidiosis, are pathogenic “water molds” in the class Oomycetes. Although they are often grouped with fungi because they grow on mycologic media and produce hyphal structures in tissue, they differ from true fungi in producing motile, flagellate zoospores; having cell walls that lack chitin; and having cell membranes that generally lack ergosterol. Both pythiosis and lagenidiosis cause lesions characterized by eosinophilic and pyogranulomatous inflammation associated with broad, irregularly branching, sparsely septate hyphae; and as a result they are often confused with zygomycosis (infections caused by true fungi in the class Zygomycetes, which produce similar lesions). Although the clinical syndromes associated with P. insidiosum infection have been described for many decades, Lagenidium spp. have only been recognized as mammalian pathogens since 1999.

Pythiosis P. insidiosum infection is a devastating and often fatal cause of gastrointestinal or cutaneous lesions in dogs and cats. In small animal patients, pythiosis is encountered most often in the southeastern United States but has also been identified in animals living in New Jersey, Virginia, Kentucky, southern Illinois, Indiana, Oklahoma, Missouri, Kansas, Arizona, California, and the Cayman Islands. Young large-breed dogs (especially outdoor working breeds such as Labrador retrievers) are most often infected. In cats specific breed and sex predilections have not been observed in the few cases that have been reported to date. However, the development of cutaneous pythiosis in very young animals appears to occur more often in cats than in dogs. Of 27 cats with cutaneous pythiosis diagnosed through my laboratory in the past 8 years, 11 were less than 1 year old, with an age range of 4 months to 9 years. The infective form of P. insidiosum is thought to be the motile biflagellate zoospore, which is released into aquatic environments and likely causes infection by encysting in damaged skin or gastrointestinal mucosa. Many dogs with pythiosis have a history of recurrent exposure to warm freshwater habitats. However, disease is also identified regularly in suburban house dogs with no history of access to lakes or ponds. Affected animals typically are immunocompetent and otherwise healthy.

Clinical Findings Gastrointestinal Pythiosis In dogs gastrointestinal pythiosis typically results in severe, segmental transmural thickening of the ­stomach, small intestine, colon, rectum, or rarely the esophagus. The ­gastric 1268

outflow area, proximal duodenum, and ileocolic junction are the most frequently affected locations; and it is not unusual to find two or more segmental lesions in the same patient. Mesenteric lymphadenopathy is common but most often represents reactive hyperplasia rather than infection. Involvement of the mesenteric root may cause severe enlargement of mesenteric lymph nodes, which are typically embedded in a single large, firm granulomatous mass that is palpable in the midabdomen. Extension of disease into mesenteric vessels may result in bowel ischemia, infarction, perforation, or acute hemoabdomen. In addition, infection in gastrointestinal tissues may extend into contiguous organs such as pancreas and uterus. Gastrointestinal pythiosis is rare in cats but was recently described in two young adult male cats with focal intestinal lesions that were amenable to surgical resection (Rakich, Grooters, and Tang, 2005). Clinical signs associated with gastrointestinal pythiosis include weight loss, vomiting, diarrhea, and hematochezia. Physical examination often reveals a very thin body condition and a palpable abdominal mass. Signs of systemic illness such as lethargy or depression typically are not present unless intestinal obstruction, infarction, or perforation occurs. Laboratory abnormalities that may be associated with pythiosis include eosinophilia, anemia, hyperglobulinemia, hypoalbuminemia, and rarely hypercalcemia. Abdominal radiography and sonography usually reveal severe segmental thickening of the gastrointestinal tract, an abdominal mass, and/or mesenteric lymphadenopathy. Cutaneous Pythiosis Cutaneous pythiosis in dogs typically causes nonhealing wounds and invasive masses that contain ulcerated nodules and draining tracts, most often involving the extremities, tail head, ventral neck, or perineum. In contrast to gastrointestinal pythiosis, regional lymphadenopathy in dogs with cutaneous pythiosis usually reflects extension or postsurgical recurrence of infection rather than just reactive inflammation. Cutaneous and gastrointestinal lesions are rarely encountered together in the same patient. Cats with pythiosis most often present with nasopharyngeal lesions; invasive subcutaneous masses in the periorbital, tail head, or inguinal regions; or draining nodular lesions or ulcerated plaquelike lesions on the extremities, sometimes centered on the digits or footpad. In contrast to dogs, cats with pythiosis often have firm, nodular, subcutaneous lesions without overlying cutaneous lesions or alopecia.

Diagnosis Cytology and Histopathology In dogs with pythiosis pyogranulomatous and eosinophilic inflammation is often apparent on cytologic evaluation of

exudate from draining tracts, impression smears made from ulcerated skin lesions, or fine-needle aspirates of enlarged lymph nodes or thickened gastrointestinal tissues. Hyphae are observed occasionally, and their morphologic appearance (broad, rarely septate with tapered, rounded ends) in conjunction with a typical inflammatory response can provide a tentative diagnosis of pythiosis, lagenidiosis, or zygomycosis. Microscopic examination of macerated tissue that has been digested in 10% potassium hydroxide may be more likely to reveal hyphal elements than other cytologic specimens. Histologically pythiosis is characterized by eosinophilic pyogranulomatous inflammation. Affected tissues contain multiple foci of necrosis surrounded and infiltrated by neutrophils, eosinophils, and macrophages. In addition, discrete granulomas composed of epithelioid macrophages, plasma cells, multinucleate giant cells; and fewer neutrophils and eosinophils are often observed. Organisms typically are found within areas of necrosis or at the center of granulomas. Vasculitis is present occasionally. In gastrointestinal pythiosis inflammation centers on the submucosal and muscular layers rather than the mucosa and lamina propria. Therefore the diagnosis of pythiosis may be missed on endoscopic biopsies that fail to reach deeper tissues. Similarly, disease in animals with cutaneous pythiosis typically is found in the deep dermis and subcutis, necessitating deep wedge biopsies rather than punch biopsies for optimal evaluation. P. insidiosum hyphae are not visualized routinely on H&E-stained sections but may be identified as clear spaces surrounded by a narrow band of eosinophilic material. Hyphae are readily visualized in sections stained with Gomori’s methenamine silver (GMS) but usually do not stain well with periodic acid–Schiff (PAS). Pythium hyphae are broad (mean, 4 μm; range, 2 to 7 μm), infrequently septate, and occasionally branching (usually at right angles). Culture Isolation of P. insidiosum from infected tissues is not difficult when appropriate sample handling and culture techniques are used. For best results room temperature (i.e., not refrigerated) tissue samples should be wrapped in a saline-moistened gauze sponge and shipped at ambient temperature to arrive at the laboratory within 24 hours. Small pieces of fresh, nonmacerated tissue should be placed directly on the surface of vegetable extract agar supplemented with streptomycin and ampicillin (or an alternative selective medium) and incubated at 37 ° C. Growth typically is observed within 12 to 24 hours. Isolation of P. insidiosum from swabs of exudate collected from draining skin lesions is generally unsuccessful. Identification of P. insidiosum should be based on morphologic features; growth at 37 ° C; production of motile, biflagellate zoospores; and, if possible, species-specific polymerase chain reaction (PCR) amplification (Grooters and Gee, 2002) or ribosomal ribonucleic acid (rRNA) gene sequencing. Although production of zoospores is an important supporting feature for the identification of pathogenic Oomycetes, it is not specific for P. insidiosum. Speciesspecific PCR amplification can also be used to identify P. insidiosum deoxyribonucleic acid (DNA) in fresh, frozen, or paraffin-embedded tissues.

Chapter  278  Pythiosis and Lagenidiosis

1269

Serology A highly sensitive and specific enzyme-linked immunosorbent assay (ELISA) for the detection of anti–P. insidiosum antibodies in dogs and cats is currently available through my laboratory (Grooters et al., 2002a). In addition to providing a means for early, noninvasive diagnosis, this assay is also very useful for monitoring response to therapy. Following complete surgical resection of infected tissues, a dramatic decrease in antibody levels is typically detected within 2 to 3 months. In contrast, antibody levels remain high in animals that go on to develop clinical recurrence following surgical treatment. In animals treated medically antibody levels change much more slowly, but I have observed significant decreases coincident with clinical improvement within 3 to 4 months of initiating medical therapy for ­nonresectable disease. Immunohistochemistry Several different immunohistochemical techniques have been used previously to confirm the diagnosis of pythiosis. However, the specificity of the antibodies used in these assays has not always been well established. A more recently developed polyclonal anti-P. insidiosum antibody raised in chickens and adsorbed with Lagenidium and Conidiobolus hyphae appears to be highly specific for the immunohistochemical detection of P. insidiosum hyphae in tissues. Immunohistochemical staining of tissues for diagnostic purposes using this antibody is available through the author’s laboratory.

Therapy Aggressive surgical resection of all infected tissues is the treatment of choice for pythiosis. In animals with cutaneous lesions confined to a single distal extremity, amputation should be recommended. In patients with gastrointestinal pythiosis segmental lesions should be resected with 3- to 4-cm margins whenever possible. Despite the fact that mesenteric lymphadenopathy is almost always present, P. insidiosum hyphae typically are absent in enlarged mesenteric nodes. Therefore the presence of nonresectable mesenteric lymphadenopathy should not dissuade the surgeon from pursuing complete resection of a segmental bowel lesion. However, enlarged regional lymph nodes should always be biopsied for prognostic information. Unfortunately most dogs with gastrointestinal pythiosis are not presented to a veterinarian until late in the course of disease, when complete excision is impossible. In addition, the anatomic location of the lesion may prevent complete surgical excision when the esophagus, gastric outflow tract, rectum, or mesenteric root is involved. Local postoperative recurrence of pythiosis is common (especially when wide surgical margins cannot be achieved) and can occur either at the site of resection or in regional lymph nodes. For this reason medical therapy with itracon­ azole (10 mg/kg q24h orally [PO]) and terbinafine (5 to 10 mg/kg q24h PO) is recommended for at least 2 to 3 months after surgery. To monitor for recurrence, ELISA serology should be performed before (or within 7 days of) and 2 to 3 months after surgery. In animals that have had a complete surgical resection and have no recurrence of disease, serum antibody levels drop 50% or more within 3 months of

1270

Section  XIII  Infectious Diseases

surgery. If this occurs, medical therapy can be discontinued, with optional subsequent reevaluation of serum antibody levels in 2 to 3 months. In my experience surgery is curative in a majority of animals with a distal limb lesion treated with amputation or with a midjejunal lesion that the surgeon believes was completely resected with good margins. Medical therapy for nonresectable pythiosis is typically unrewarding, likely because ergosterol (the target for most currently available antifungal drugs) is generally lacking in the Oomycete cell membrane. Despite this fact, I have observed clinical and serologic cures in a number of patients treated with a combination of itraconazole (10 mg/kg q24h PO) and terbinafine (5 to 10 mg/kg q24h PO). Although the percentage of animals responding is still quite low (16 weeks)

Booster Interval

Administer one dose at 6-8 weeks of Administer two doses 3-4 weeks age and then every 3-4 weeks until apart. 14-16 weeks of age.

Administer one dose 1 year following completion of the initial series and then every 3 years thereafter.

Administer one dose at 12-16 weeks of age.

Administer one dose 1 year following administration of the first dose and then every 3 years thereafter.

Administer one dose.

Requirements for canine rabies vaccination are established by state and/or local statutes and may differ from the recommendations listed here.

Table 279-2 Noncore Canine Vaccines and Recommendations for Administration Noncore (Optional) Vaccines Bordetella bronchiseptica + Parainfluenza Avirulent-live (intranasal administration ONLY)

Bordetella bronchiseptica Killed, or antigen extract

Primary Puppy Series (≤16 weeks)

Booster Interval

A single dose is recommended by A single dose the manufacturers and may be given as early as 3-4 weeks of age. Two doses 2-4 weeks apart are suggested for best results. May be given as early as 3-4 weeks of age.

Annually; animals in a high risk/­ exposure environment may ­benefit from a booster if longer than 6 months since the previous dose.

Administer two doses 2-4 weeks apart beginning as early as 8 weeks of age.

Administer two doses 2-4 weeks apart.

Annually; animals in a high risk/­ exposure environment may b ­ enefit from a booster if longer than 6 months since the previous dose.

Administer two doses, 2 to 4 weeks apart.

Annual booster is recommended for dogs with a defined risk of exposure. Vaccination is not recommended for all dogs. Exposure risk should be considered before recommending.

Administer two doses 2-4 weeks apart.

Annual booster is recommended for dogs with a defined risk of exposure. Vaccination is not recommended for all dogs.

Leptospira interrogans (Serovars: canicola, icteroAdminister two doses 2-4 weeks haemorrhagiae, pomona, apart beginning as early as grippotyphosa) Various two12 weeks of age. way and four-way combina- (Vaccination of dogs less than 12 tions are available. weeks of age is generally not Killed bacterin recommended.) Lyme borreliosis Recombinant or Administer two doses 2-4 weeks killed bacterin apart beginning as early as 12 weeks of age.

note:

Primary Adult Series (>16 weeks)

Unless indicated, all vaccines may be administered by the subcutaneous route.

Noncore or Optional Vaccines All dogs do not share equal risk of exposure to infectious agents. Principle variables affecting exposure risk include age, breed, health status, life style, geographic location, and travel history. Vaccines classified as noncore are those that a veterinarian may recommend or not recommend

based on a reasonable assessment of risk in the individual patient. The 2006 AAHA Canine Vaccine Guidelines have classified the following vaccines as noncore: distemper-measles, all Bordetella bronchiseptica vaccines, parainfluenza virus, Borrelia burgdorferi (Lyme borreliosis), and Leptospira interrogans (all four serovars). The frequency

1274

Section  XIII  Infectious Diseases

of administration for noncore vaccines differs depending on the antigen type (avirulent live [topical] versus killed [parenteral]) and the manufacture’s recommendation. When noncore vaccines are indicated for administration in adult dogs, annual administration generally is recommended. Because of the variation among individual products, veterinarians should be familiar with dosing, frequency, and administration requirements of the individual vaccine product selected. Veterinarians are also urged to consult the “Comments and Recommendations” section listed in the summary table of the full text version of the Guidelines (Part 1) to review specific recommendations on administering a particular vaccine type.

Conditionally Licensed Vaccines Two new canine vaccines, conditionally licensed by the U.S. Department of Agriculture (USDA), are available throughout the United States: Crotalus atrox toxoid (western diamondback rattlesnake vaccine) and Porphyromonas spp. vaccine (an aid in the prevention of periodontitis). Neither of these vaccines has been subjected to conventional challenge studies. Although a reasonable expectation of efficacy exists, there is currently minimal field validation of efficacy. The AAHA Canine Vaccine Task Force elected not to categorize these vaccines as core, noncore, or “not recommended.” Veterinarians considering the use of either of these products are encouraged to review the product literature and, when feasible, the experience offered by colleagues who have experience with the individual product.

Vaccines Not Recommended for Routine Administration Several vaccine types have been classified by the AAHA Canine Vaccine Task Force as “not recommended.” Reasons for assigning such a classification to a particular vaccine include such factors as lack of vaccine efficacy, diminished efficacy compared to alternative antigen types (e.g., killed virus vaccines are expected to be less efficacious than MLV vaccines), and safety. Vaccines classified as “not recommended” are: CAV-1, Giardia lamblia, coronavirus (killed virus and MLV), killed CPV, killed CAV-2, and topical (MLV) CAV-2. Each of these vaccines is currently licensed by the USDA and may be selected for administration to dogs at the discretion of the clinician. Veterinarians are encouraged to consult the full text of the 2006 Canine Vaccine Guidelines for additional discussion behind the reason an individual vaccine was given this classification.

Guidelines for Shelter-Housed Dogs The frequent introduction of healthy and sick dogs, seasonal variation in population density, and variable risk of exposure among shelter populations make it impractical to define specific “core” vaccine recommendations that will serve all facilities comparably. Only vaccines that are expected to demonstrate a clear benefit against common

and high-threat shelter infections are recommended. The AAHA Canine Vaccine Task Force recognizes the need for individual shelters to tailor vaccination requirements in a manner that is consistent with exposure risk and financial constraints of the individual facility. Because of the high exposure risk faced by shelter-housed dogs, ­vaccination recommendations made within this section of guidelines are considerably more aggressive than those recommended in general practice. All dogs should be inoculated with CDV, CPV, and CAV-2 vaccine at the time of entry into the facility. Delaying vaccination by even a few hours could pose significantly increased risk of infection for individual dogs, especially puppies. Vaccines should be MLV; alternatively a recombinant vaccine may be used interchangeably with MLV vaccine for CDV. The recombinant CDV vaccine has the added advantage of immunizing puppies as young as 8 weeks of age even in the presence of passively acquired maternal antibody. With the exception of rabies, killed virus vaccines should not be used in animal shelter vaccination program. When feasible, a single dose of intranasal B. bronchiseptica (avirulent live) combined with parainfluenza virus is preferred and should also be administered at the time of entry into the facility. Vaccination is recommended as early as 4 weeks of age (3 weeks of age for intranasal B. bronchiseptica), particularly when infection rates within the facility are considered to be high. Vaccines for CDV, CPV, and CAV-2 are repeated every 2 weeks until 16 weeks of age. Dogs over 16 weeks of age should receive a second dose 2 weeks later if still in the facility. A 1-year rabies vaccine is recommended at the time of release from the shelter. Several options for alternative protocols are included in the Guidelines. Individuals seeking detailed information on recommendations for vaccinating shelter-housed dogs should refer to Part 2 of the AAHA Canine Vaccine Guidelines (www.aahanet.org).

Suggested Reading Böhm M et al: Serum antibody titres to canine parvovirus, adenovirus, and distemper, Vet Rec 154:457, 2004. Carmichael LE: Canine viral vaccines at a turning point: a ­personal perspective. In Schultz RD, editor: Advances in veterinary medicine 41: veterinary vaccines and diagnostics, San Diego, 1999, Academic Press, p 289. Greene CE, Schultz RD: Immunoprophylaxis. In Greene CE, ­editor: Infectious diseases of the dog and cat, ed 3, St. Louis, 2006, Saunders-Elsevier, p 1068. Klingborg DJ et al: AVMA Council on Biologic and Therapeutic Agents’ report on cat and dog vaccines, J Am Vet Med Assoc 221(10):1401, 2002. Mouzin DE et al: Duration of immunity in dogs after vaccination or naturally acquired infection, J Am Vet Med Assoc 224:55, 2004. Pardo MC, Bauman JE, Mackowiak M: Protection of dogs against canine distemper by vaccination with a canarypox virus recombinant expressing canine distemper virus fusion and hemagglutinin glycoproteins, Am J Vet Res 58:833, 1997. Pardo MC et al: Immunization of puppies in the presence of maternally derived antibodies against canine distemper virus, J Comp Path 137:572, 2007.

C hapter  

280

Feline Vaccination Guidelines Richard B. Ford, Raleigh, North Carolina

I

n November 2006 the American Association of Feline Practitioners (AAFP) published the latest report of the Feline Vaccine Advisory Panel outlining current feline vaccination recommendations (Richards et al, 2006). This was the first update published since 2000 and provided considerable new information on feline vaccines and vaccination practices. Whether or not an individual veterinarian intends to incorporate the 2006 feline vaccination recommendations into his or her practice, the current document is worthy of review and consideration. In addition to basic recommendations on vaccine administration, the report includes critical information on the selection and use of feline vaccines in practice. As more feline vaccines are introduced, veterinarians have the increasingly complex task of ensuring that individual patients are vaccinated against diseases that pose a realistic threat to the individual animal’s health yet avoid the risk of adverse reactions associated with vaccination. There can be little argument that routine vaccination programs remain an exceptional health care value for pets today. Yet the proliferation of new vaccines and new vaccine technology give emphasis to the fact that all vaccines are not necessarily alike. Likewise all cats do not share the same level of risk for exposure to infectious pathogens. It is the objective of the AAFP Feline Vaccine Advisory Panel to develop a document that will facilitate the efforts of practitioners in developing rational vaccination protocols for feline patients. As written, the Advisory Panel’s report is not intended to represent a universal protocol applicable for all cats, nor is it intended to represent the standard of care by which all cats must be vaccinated. Although certainly there is no requirement for individual practices to implement the recommendations in the report, this document does contain important, relevant information pertaining to the routine selection and use of feline vaccines in clinical practice. The entire report is available at www.aafponline.org, (search: Practice Guidelines).

Highlights of the 2006 AAFP Feline Vaccine Guidelines The 2006 Report of the AAFP Feline Vaccine Advisory Panel is the most comprehensive review of feline vaccines and vaccination programs yet published. The report is comprehensive and includes 14 separate sections that address topics such as basic vaccine immunology, the types of vaccines available today, and recommendations on routes of vaccine administration. The report also includes a number of special considerations that pertain directly to the administration of vaccines in cats such as age, breed, and vaccination intervals. Additional special

considerations include administration of vaccine to cattery cats, lactating queens, sick cats, retrovirus-infected cats, cats receiving corticosteroids, and cats having a prior history of vaccine-associated adverse reactions (events). Updated information on controversial topics such as the extended duration of immunity for the feline (core vaccines) and the triennial booster recommendations is also presented. Of importance to all practitioners is the section on legal considerations, which centers on liability associated with vaccinating cats. Topics on vaccine standards of care and informed consent are also presented. The section on vaccine adverse events, also called adverse reactions, highlights the exceptional safety record of vaccines yet outlines concerns over the lack of available data for the types of reactions that are believed to occur. Much of the discussion addresses vaccine-associated fibrosarcomas, perhaps the single most important vaccine adverse event that occurs in companion animal medicine. Veterinarians in the United States are encouraged to report feline vaccine adverse events, known or suspected, to the Center for Veterinary Biologics (CVB, www.aphis.usda.gov/ vs/cvb) online and to the vaccine manufacturer (manufacturers are required to forward reports to the CVB). One noteworthy addition to the report is the section on vaccination of shelter-housed cats. This section complements information found in the 2006 American Animal Hospital Association (AAHA) Canine Vaccine Guidelines, which is available on the AAHA website available at www. aahanet.org (also see Chapter 279). Furthermore, new recommendations on the vaccination of cats in trap-neuter-return programs and kitten socialization classes are included. The report also includes six appendices that focus on issues ranging from vaccination site recommendations to vaccine handling and storage requirements.

Core Vaccines For several years the primary vaccination series for kittens has been a single dose administered at 9 and 12 weeks of age. The current guidelines, however, recommend that the first dose of core vaccines (feline parvovirus [panleukopenia virus], herpesvirus-1, and calicivirus) be administered as early as 6 weeks of age and then every 3 to 4 weeks until 16 weeks of age. This should be followed by a booster at 1 year of age and every 3 years thereafter. A rabies vaccine, also recommended as core for all cats, can be administered as a single dose as early as 12 weeks of age; a booster is administered 1 year later. State or local rabies ordinances that dictate different requirements have precedence over any recommendations published in the 2006 AAFP Feline Vaccine Advisory Panel Report (Tables 280-1 and 280-2). 1275

1276

Section  XIII  Infectious Diseases

Table 280-1 Core Feline Vaccines and Recommendations for Administration Core Vaccines Parvovirus (Panleukopenia) Herpesvirus-1 and calicivirus Modified-live (nonadjuvanted) or killed (adjuvanted) (subcutaneous or intranasal administration) Rabies Recombinant (nonadjuvanted) Rabies Killed: 1 year Killed: 3 year (adjuvanted)

note:

Primary Kitten Series (≤ _16 weeks)

Primary Adult Series (>16 weeks)

Administer one dose as early as 6 weeks of age and then every 3-4 weeks until 16 weeks of age.

Administer two doses 3-4 weeks apart.

Administer one dose at 12-16 weeks of age.

Administer one dose.

Administer one dose at 12-16 weeks of age.

Administer one dose.

Booster Interval Administer one dose 1 year following completion of the initial series and then every 3 years thereafter. note: It is still appropriate to recommend annual booster against feline ­herpesvirus-1 and feline calicivirus for cats housed in high risk environments. Annually

Administer one dose 1 year following administration of the first dose and then every 3 years thereafter.

Requirements for feline rabies vaccination are established by state and/or local statutes and may differ from the recommendations listed here.

Table 280-2 Noncore Feline Vaccines and Recommendations for Administration Noncore (Optional) Vaccines

Primary Kitten Series (≤_16 weeks)

Feline Leukemia Recombinant (nonadjuvanted) Administer two doses 3-4 (transdermal administration only) weeks apart beginning as early as 12 weeks of age.

Primary Adult Series (>16 weeks)

Booster Interval

Administer two doses 3-4 weeks apart.

Annual booster; booster vaccination is not recommended for all cats. Exposure risk should be considered before recommending.

Administer two dose 3-4 weeks apart beginning as early as 12 weeks of age.

Administer two doses 3-4 weeks apart.

Chlamydophila felis Avirulent live (nonadjuvanted)

Administer two doses 3-4 weeks apart beginning as early as 12 weeks of age.

Administer two doses 3-4 weeks apart.

Chlamydophila felis Killed (adjuvanted)

Administer two doses 3-4 weeks apart beginning as early as 12 weeks of age.

Administer two doses 3-4 weeks apart.

Annual booster; booster vaccination is not recommended for all cats. Exposure risk should be considered before recommending. Annual booster; booster vaccination is not recommended for all cats. Exposure risk should be considered before recommending. Annual booster; booster vaccination is not recommended for all cats. Exposure risk should be considered before recommending.

Administration of three initial doses is required. Beginning as early as 8 weeks of age, administer two additional doses 2-3 weeks apart.

Administration of three initial doses is required. Each dose should be administered 2-3 weeks apart.

Annual booster; booster vaccination is not recommended for all cats. Exposure risk should be considered before recommending. note: A single dose of feline immunodeficiency virus (FIV) vaccine can result in a false-positive test result on all commercial FIV tests for at least 1 year.

Administer a single dose as early as 8 weeks of age.

Administer a single dose.

Administer annually, but only in cats with established risk of exposure.

Feline Leukemia Killed (adjuvanted)

Feline Immunodeficiency Virus Killed (adjuvanted)

Bordetella bronchiseptica Avirulent live (nonadjuvanted) (intranasal only)

note: Routine vaccination of cats against feline infectious peritonitis virus and Giardia lamblia is not generally recommended. Unless otherwise stipulated, all feline vaccines should be administered by the subcutaneous route.



Feline Leukemia Virus Vaccine Feline leukemia virus (FeLV) vaccine continues to be listed as noncore. However, since kittens are more likely than adults to become persistently viremic following exposure, the Advisory Panel highly recommends that all kittens receive a two-dose primary series, beginning as early as 8 weeks of age, and a booster 1 year after completion of the initial series. There are no published studies documenting vaccine duration of immunity beyond 1 year. Therefore adults deemed to be at sustained risk of exposure (e.g., outdoor cats) should be vaccinated annually. Documentation of a negative FeLV (antigen) test is recommended before administration of the FeLV vaccine.

Vaccination of Retrovirus-Positive Cats Studies evaluating the ability of FeLV- and feline immunodeficiency virus (FIV)–infected cats to mount a protective immune response subsequent to vaccination vary. However, it is the recommendation of the Advisory Panel that feline core vaccines should be administered to healthy, retrovirus-positive cats. It is left to the discretion of the clinician whether the risk of exposure in an individual cat justifies vaccine administration. There is no known therapeutic value in administering either an FeLV or FIV vaccine to a retrovirus-infected cat.

Adjuvanted versus Nonadjuvanted Feline Vaccine Based on the finding of several published studies, the association between adjuvanted vaccine use and the development of vaccine-associated fibrosarcomas is deemed to be sufficiently compelling that the Advisory Panel recommends that “veterinarians use less inflammatory products whenever possible.” Avoiding adjuvanted vaccines is not a guarantee that an individual cat will never develop cancer at an injection site; however, simply recommending that injectable vaccines be administered as low (distal) on the leg as feasible to facilitate amputation remains an impractical solution to the vaccine-associated sarcoma problem. At this writing, all feline killed virus and killed bacterial vaccines contain adjuvant. Modified-live virus, avirulent live bacteria (e.g., intranasal administration), and recombinant vaccines do not contain adjuvant.

Vaccination Against Feline Immunodeficiency Virus Particularly important is the fact that a single dose of the FIV vaccine can result in the production of antibodies that cause (false)-positive test results on all commercially available FIV tests. Vaccine-induced antibodies can also be passed from queen to kittens via colostrum and interfere with testing beyond the age of weaning. FIV test interference in adult vaccinated cats has been shown to persist for at least 1 year. In kittens test interference derived from ingestion of colostrum appears to wane by 12 weeks of age. Cats receiving the current FIV vaccine should be permanently identified (e.g., microchip).

Chapter  280  Feline Vaccination Guidelines

1277

Vaccines Not Recommended for Routine Administration Consistent with recommendations published in 2000, the Advisory Panel continues to stipulate that vaccination of cats against feline coronavirus (FCoV), to prevent feline infectious peritonitis (FIP) infection, and Giardia lamblia is “not generally recommended.” Although considerable controversy surrounds the ability of the FIP vaccine to protect cats from infection, most studies have shown little or no benefit from routine inoculation. The G. lamblia vaccine contains chemically inactivated (killed) trophozoites and an adjuvant. In independent studies administration of this vaccine did not lessen cyst shedding in experimentally infected cats when compared with control cats.

Virulent Systemic Feline Calicivirus Vaccine In January 2007 a killed, adjuvanted vaccine was licensed in the United States as an aid in preventing infection with virulent systemic feline calicivirus (VS-FCV). Earlier a bivalent, killed (nonadjuvanted) calicivirus vaccine was licensed in the United Kingdom. Neither of these vaccines was addressed is the 2006 Advisory Panel Report. An amendment to the report addressing recommendations on the use of the VS-FCV vaccine is expected later in 2008. VS-FCV is a highly contagious, severe infection that occurs predominantly in adult cats; most reports involve cats residing in shelters. At least one outbreak has been documented in a veterinary hospital housing shelter cats. However, in the last decade fewer than 10 outbreaks have been documented in the United States and United Kingdom combined. Vaccine efficacy has been demonstrated in cats experimentally challenged with a calicivirus strain that was homologous with the virus strain used in the vaccine. However, the literature currently does not support the ability of a single VS-FCV strain to provide cross-protection against VS-FCVs that may be encountered in cats in future outbreaks. This vaccine is neither a replacement for nor an alternative to the combined calicivirus vaccine plus feline herpesvirus-1 administered to cats for the prevention of viral upper respiratory infections.

Vaccination of Shelter-Housed Cats Vaccination of cats presented to and maintained in a shelter-type environment presents a number of unique and challenging issues to veterinarians attempting to manage morbidity and limit mortality associated with contagious infectious diseases, particularly panleukopenia, ­herpesvirus-1, and calicivirus infection. In general, the Advisory Panel recommends that all cats receive vaccine against panleukopenia, herpesvirus-1, and calicivirus on entry to the facility; a 1-year rabies vaccine is administered at the time of release. There are no indications for admini­ stration of FeLV, FIV, G. lamblia, and Bordetella bronchiseptica vaccine in the shelter environment. One exception for consideration includes vaccination of kittens against FeLV when housing requirements dictate that unrelated kittens be housed together. For specific recommendations on individual vaccines, the full text of the 2006 Feline Vaccine Guidelines should be consulted.

1278

Section  XIII  Infectious Diseases

References and Suggested Reading Gaskell RM et al: Veterinary Products Committee (VPC) Working Group Report of Feline and Canine Vaccination. Final Report to the VPC, London, 2002, Dept Environmental, Food and Rural Affairs (Monograph). Greene CE, Schultz RD: Immunoprophylaxis. In Greene CE, ­editor: Infectious diseases of the dog and cat, ed 3, St Louis, 2006, Saunders, p 1069. Lappin MR: Use of serologic tests to predict resistance to feline herpesvirus-1, feline calicivirus, and feline parvovirus infection in cats, J Am Vet Med Assoc 220:38, 2002.

C hapter  

Meyer EK: Vaccine-associated adverse events, Vet Clin North Am Small Anim Pract 31:493, 2001. Mouzin DE: Duration of serologic response to three viral antigens in cats, J Am Vet Med Assoc 224:61, 2004. Richards JR et al: The 2006 American Association of Feline Practitioners Feline Advisory Panel Report, J Am Vet Med Assoc 229(9):1405, 2006. Scott FW, Geissinge CM: Long-term immunity in cats vaccinated with an inactivated trivalent vaccine, Am J Vet Res 60:652, 1999.

281

Feline Leukemia Virus and Feline Immunodeficiency Virus Katrin Hartmann, Munich, Germany

T

he three feline retroviruses, feline immunodeficiency virus (FIV), feline leukemia virus (FeLV), and feline foamy virus (FeFV), are global and widespread. Although all three viruses are in the family Retroviridae, they differ in their potential to cause disease. FeFV ­(previously known as feline syncytium-forming virus, FeSFV), a spumavirus, is not associated with disease; thus routine testing is not performed. FIV, a lentivirus that shares many properties with human immunodeficiency virus (HIV), can cause an acquired immune deficiency syndrome in cats, with increased risk for opportunistic infections, neurologic diseases, and tumors. In most naturally infected cats FIV infection does not cause a severe clinical syndrome, and with proper care FIV-infected cats can live many years. Many in fact die at an older age from causes completely unrelated to FIV infection. In a study of naturally FIVinfected cats, the rate of progression was variable, with death occurring in about 18% of infected cats within the first 2 years of observation (about 5 years after the estimated time of infection). An additional 18% developed increasingly severe disease, but more than 50% remained clinically asymptomatic during the 2 years of observation (Levy et al., 2000). FIV infection has little impact on a cat population, and does not reduce the number of cats in a household. Thus overall survival time is not ­necessarily

shorter than in uninfected cats, and quality of life is usually fairly high over an extended period of time. FeLV, an oncornavirus, is the most pathogenic of the three viruses. Historically it was considered to account for more disease-related deaths and clinical syndromes than any other single infectious agent in cats. More recently the prevalence and consequently the importance of FeLV as a pathogen in cats have been decreasing, mainly because of testing and eradication programs and the relatively common use of FeLV vaccines. The death rate of persistently viremic cats in multicat households is approximately 50% in 2 years and 80% in 3 years but is lower in cats kept strictly indoors in single-cat households. Despite the fact that persistent FeLV viremia is associated with a decrease in life expectancy, many owners elect to provide treatment for the clinical syndromes that accompany infection. With proper care, many FeLV-infected cats kept indoors only may live for many years with good quality of life. A decision for treatment or for euthanasia of a cat should never be based solely on the presence of a retrovirus infection. FIV- and FeLV-infected cats are subject to the same diseases that befall cats free of those infections, and illness in a given cat may not be related to the retrovirus infection at all. However, in all cats, healthy or sick, FIV and FeLV status should be known because retrovirus infection impacts health status and long-term patient management.



Chapter  281  Feline Leukemia Virus and Feline Immunodeficiency Virus

1279

Management of Retrovirus-Infected Multicat Households

Management of Individual Retrovirus-Infected Cats

When a cat in a multicat household is diagnosed with a retrovirus infection, all cats in that household should be tested to determine their virus status. If positive and negative cats are identified within the same household, the owner must be informed of the potential danger to uninfected cats and told that the best method of preventing spread of infection is to isolate the infected individuals and prevent them from interacting with housemates. However, despite this admonition, the overall risk of transmission between these cats is not very high for either infection. FIV transmission in households with a stable social cat environment is rare because FIV is mainly transmitted through biting and fighting; if no fights occur, FIV will not be transmitted. In long-term studies of households with FIV-infected cats, few additional cats became FIV positive over time; in some households no transmission occurred over many years. All cats in these households should be neutered, and it is crucial not to introduce a new cat into the household since this might lead to fights and to transmission, even between cats that have lived together peacefully for a long time. The benefit of FIV vaccination of FIV-negative cats in households with an FIV-positive cat is controversial (see Chapter 280). The vaccine currently available has not been tested under these conditions. Usually the FIV subtype of the infected cat is unknown, and cross-protection by the vaccine against some FIV subtypes (e.g., the frequently found subtype B) is uncertain. Because the vaccine contains whole virus, cats respond to vaccination by producing antibodies that are indistinguishable from those produced during natural infection. Therefore all vaccinated cats will be antibody positive, and assessment of their true infection status can be difficult. Ideally, before vaccination is considered the veterinarian should ensure that the virus in the infected cat can be detected by polymerase chain reaction (which is only possible in 50% to 80% of cases). Only if the virus strain of the infected cat is detectable by PCR will it be possible to later identify another cat in the household that might become infected despite vaccination. If an FeLV-infected cat has lived for some time in an otherwise FeLV-negative household, the other cats that have been together with the FeLV-infected cat will already have been infected. Thus, these cats are most likely immune to new infection, and an owner may elect to keep all of the cats together. However, studies in cluster households have shown that virus-neutralizing antibodies do not persist for life; thus a previously immune cat may become viremic. This may be the result of new infection or reactivation of a long-persisting latent infection. The risk of infection in adult FeLV-negative cats is approximately 10% to 15% if they have lived with a viremic cat for several months. If owners refuse to separate housemates, the uninfected cats should receive FeLV vaccination to enhance their natural level of immunity. However, owners should be informed that vaccination does not provide sufficient levels of protection in these environments of high viral exposure. If the household is closed to new cats, the FeLV-negative cats tend to outlive the infected cats.

The most important life-prolonging advice the veterinarian can advance to owners of retrovirus-infected cats is “keep the cats strictly indoors”. This not only avoids spread to other cats in the neighborhood, but also prevents exposure of the immunosuppressed, retrovirusinfected cat to infectious agents carried by other animals. In FIV-infected cats, secondary infections not only cause clinical signs but also may lead to progression of the FIV infection itself. This is probably not the case in FeLV infection in which the retroviral infection itself it more pathogenic and progresses relatively independently of cofactors. “Routine vaccination” of retrovirus-infected cats is subject to much discussion. It is the recommendation of an Advisory Panel on Feline vaccination that feline core vaccines should be administered to healthy, retrovirus­positive cats at risk (see Chapter 280 for details). The author’s recommendations follow. While there is no scientific proof that retrovirusinfected cats are at increased risk from modified-life virus (MLV) vaccines, inactivated vaccines are recommended out of concern that MLV vaccines given to immune-suppressed animals may regain pathogenicity. FIV-infected cats are susceptible to secondary infection (thus regular vaccination would seem indicated). Studies have shown that healthy FIV-infected cats are able to mount appropriate levels of protective neutralizing antibodies after vaccination. However, it is the author’s opinion that vaccines should not be given to FIV-infected cats, if strictly kept indoors because not only immune ­suppression, but also immune stimulation, can lead to progression of FIV infection by altering the balance between the immune system and the virus. Stimulation of FIV-infected lymphocytes is known to promote virus production in vitro. In vivo vaccination of chronically infected FIV-infected cats with a synthetic peptide was associated with a decrease in the CD4/CD8 ratio. Thus the potential tradeoff to protection from infection with vaccination is progression of FIV infection secondary to increased virus production. If FIV-infected cats are kept strictly indoors, the risk of secondary infections is lower than the possible adverse effects of vaccination. It should be noted that in some countries or states legal requirements for rabies vaccination may supersede these issues. The author, however, agrees with the recommendation that FeLV-infected cats should be administered routine vaccinations. In studies of immune response to rabies vaccination, it was demonstrated that FeLV-infected cats may not be able to mount adequate immune responses. Therefore protection in an FeLV-infected cat after vaccination is not comparable to that in a healthy cat, and more frequent vaccinations than usually recommended must be considered (e.g., every 6 months), especially in cats that are allowed to go outside in areas with high rabies prevalence. Retrovirus-infected cats should have veterinary evaluations at least semiannually to promptly detect changes in health status. A complete blood count (CBC), biochemistry profile, and urinalysis should be performed at least annually

1280

Section  XIII  Infectious Diseases

(CBC every 6 months in FeLV-infected cats to detect anemia or other cytopenias associated with FeLV infection). Intact male and female retrovirus-infected cats should be neutered to reduce stress associated with estrus and mating behavior and the desire to roam outside the house or interact aggressively. Surgery is generally well tolerated by asymptomatic ­retrovirus-infected cats, but perioperative antibiotic administration should be used for all surgeries and dental procedures. Since the viruses live for only minutes outside of the host and are susceptible to all disinfectants (including common soap), simple precautions and routine cleaning procedures will prevent transmission in the hospital. Retrovirus-infected cats can be housed in the same ward as other hospitalized patients; however, they should be housed in individual cages. They may be immune suppressed and should be kept away from cats with other infectious diseases. Under no circumstances should they be placed in a “contagious disease ward” with cats suffering from infections such as viral respiratory disease. If retrovirus-infected cats are sick, prompt and accurate identification of the secondary illness is essential to allow early therapeutic intervention and a successful treatment outcome. Therefore more intensive diagnostic testing should proceed earlier in the course of illness than might be recommended for uninfected cats. Many cats with retrovirus infection respond as well as uninfected cats to appropriate medications, although a longer or more aggressive course of therapy (e.g., antibiotics) may be needed. Corti­costeroids or other immune-suppressive or bone marrow–suppressive drugs should be avoided. Griseofulvin has been shown to cause bone marrow suppression in FIV-infected cats and should not be used. Recombinant human granulocyte colony-stimulation factor (rHuG-CSF; Filgastrim) is contraindicated in neutropenic FIV-infected cats. Although it increases neutrophil counts, treatment can also lead to a significant increase in viral load in peripheral blood mononuclear cells by enhancing infection of lymphocytes or increasing expression of FIV by infected lymphocytes. Until data in FeLV-infected cats are available, rHuG-CSF therapy also cannot be recommended. Recombinant human erythropoietin (rHuEPO) may be effective in cats with nonregenerative anemia. FIV-infected cats treated with HuEPO (100 units/kg subcutaneously [SQ] q48h) showed a gradual increase in red and white blood cell counts, and increases in viral loads were not observed; thus rHuEPO appears to be safe in FIV-infected cats. No studies are available for FeLV-infected cats, but the author assumes rHuEPO will have the same positive effects. Recombinant human insulin-like growth factor-1 (rHuIGF-1) can induce thymic growth and stimulate T cell function. Treatment with rHuIGF-1 resulted in a significant increase in thymus size and thymic cortical regeneration replenishing the peripheral T cell pool in experimentally FIV-infected cats. It could be considered in young FIVinfected cats as supportive treatment, but there are no field studies so far to show its effect in naturally FIV-infected cats. Its usefulness in FeLV infection is also unknown.

Immune Modulator Therapy Immune modulators or interferon inducers are widely used in retrovirus-infected cats, especially FeLV-infected cats

(Table 282-1). Although reports of uncontrolled studies frequently suggest sometimes dramatic clinical improvement, these effects generally have not been reproduced in properly controlled studies. It has been suggested that these agents may benefit infected animals by restoring compromised immune function, thereby allowing the patient to control viral burden and recover from the disease. Most reports in the veterinary literature are difficult to interpret because of vague diagnostic criteria, lack of clinical staging or follow-up, small numbers of cats studied, absence of a placebo-treated control group, the natural variability of the course of disease, and the fact that additional supportive treatments were administered. Especially the homeopathic remedies have not been sufficiently evaluated in feline retrovirus infections and these drugs cannot be recommended. In FeLV-infected cats every immune modulator therapy should be considered very carefully. There is no conclusive evidence from controlled studies that immune modulators or alternative drugs have any beneficial effects on health or survival of asymptomatic or symptomatic FIV-infected cats. As suggested previously, nonspecific stimulation of the immune system might even be contraindicated in FIV infection because it can lead to an increase in virus replication caused by activation of latently infected lymphocytes and macrophages. Thus nonspecific immunomodulators with unknown effects are not recommended in FIV-infected cats. A number of immune modulators have been used against FeLV infection. Pind-avi (parapox virus avis) and pind-orf (parapox virus ovis) are inactivated poxviruses that belong to the so-called paramunity inducers. Their suggested mode of action is primarily induction of interferons and activation of natural killer cells. These compounds caused a sensation in Germany when it was published that their administration resulted in a cure of 80% to 100% of FeLV-infected cats, even those in moribund condition. Paramunity inducers (1 ml SQ twice a week for 6 weeks) quickly became the most commonly used ­treatment for FeLV infection in Europe. However, two placebo-controlled, double-blind trials (including 120 and 30 cats, respectively) using the same treatment protocol in naturally FeLV-infected cats under controlled conditions failed to reproduce these striking results. There were no significant differences between the cats treated with paramunity inducers and placebo-treated cats in the number of cats that terminated viremia or in any clinical, laboratory, immunologic, or virologic parameter investigated (Hartmann et al., 1998). These studies demonstrate the importance of sufficiently controlled clinical trials in the assessment of novel therapies for feline retrovirus infections. Acemannan, a water-soluble, long-chain complex carbohydrate polymer derived from the aloe vera plant, is thought to be taken up by macrophages, stimulating them to release cytokines, which in turn stimulate cell-mediated immune responses, including cytotoxicity. In one uncontrolled trial, 50 cats with natural FeLV ­infection were treated with acemannan (2 mg/kg intraperitoneally [IP] once a week for 6 weeks). After 12 weeks 71% of the cats were known to be alive, all cats remained FeLV antigen positive, and no significant change was noted in their clinical signs or hematologic parameters. There was no control group; thus assessment of the results is difficult (Sheets et al., 1991).

Chapter  281  Feline Leukemia Virus and Feline Immunodeficiency Virus



1281

Table 281-1 Treatment Options for Retrovirus-Infected Cats Drug Antiviral Drugs Zidovudine Stavudine Didanosine Zalcitabine Lamivudine Ribavirin Foscarnet Suramin T20 AMD3100 Lactoferrin

Human interferon-α   subcutaneous high dose   oral low dose Feline interferon-ω

Immune Modulators Polyriboinosinic­polyribocytidylic acid Pind-avi/Pind-orf Acemannan Staphylococcus protein A Propionibacterium acnes Bacille Calmette-Guérin (BCG) Serratia marcescens Levamisole Diethylcarbamazine Nosodes

Efficacy in vitro?

Controlled Studies in vivo?

Efficacy in vivo?

Author Opinion on Use

FIV FeLV FIV FeLV FIV FeLV FIV FeLV FIV FeLV FIV FeLV FIV FeLV FIV FeLV FIV FeLV FIV FeLV FIV

Yes Yes Yes n.d. Yes Yes Yes Yes Yes No Yes Yes Yes Yes n.d. n.d. No n.d. Yes n.d. n.d.

Yes Yes No No No No No Yes Yes No No No No No No No No No Yes No Yes

Yes No n.d. n.d. n.d. n.d. n.d. No No n.d. n.d. n.d. n.d. n.d. n.d. n.d. No n.d. Yes n.d. ±

FeLV

n.d.

No

n.d.

FIV FeLV FIV FeLV FIV FeLV

Yes Yes Yes Yes Yes Yes

No Yes No Yes Yes Yes

n.d. No ± No No ±

Effective in some cats Not effective in field cats Possibly effective Possibly effective Possibly effective Possibly effective Toxic in high dosages Toxic in high dosages Toxic in high dosages Toxic in high dosages Toxic in cats Toxic in cats Toxic Toxic Likely ineffective Likely ineffective Ineffective Likely ineffective Some effect in field cat Likely ineffective Possibly effective in stomatitis Possibly effective in stomatitis Likely ineffective Ineffective Improved survival Ineffective Ineffective Improved survival

FIV FeLV FIV FeLV FIV FeLV FIV FeLV FIV FeLV FIV FeLV FIV FeLV FIV FeLV FIV FeLV FIV FeLV

n.d. n.d. n.d. n.d. n.d. n.d. n.d. n.d. n.d. n.d. n.d. n.d. n.d. n.d. n.d. n.d. n.d. n.d. n.d. n.d.

No No No Yes No No No Yes No No No Yes No Yes No No No Yes No No

n.d. n.d. n.d. No n.d. n.d. n.d. ± n.d. n.d. n.d. No n.d. No n.d. n.d. n.d. No n.d. n.d.

Contraindicated Likely ineffective Contraindicated Ineffective Contraindicated Likely ineffective Contraindicated Possibly effective Contraindicated Likely ineffective Contraindicated Ineffective Contraindicated Ineffective Contraindicated Likely ineffective Contraindicated Ineffective Contraindicated Likely ineffective

FeLV, Feline leukemia virus; FIV, feline immunodeficiency virus; n.d., not determined; ±, some effect.

Staphylococcus protein A (SPA), a bacterial polypeptide purified from cell walls of Staphylococcus aureus Cowan I, can bind to the Fc portion of certain ­immunoglobulin G subclasses by a nonimmunologic mechanism without disturbing antigen binding and may combine with immune

complexes; stimulate complement activation; and induce T cell activation, stimulation of natural killer cells, and ­interferon production. A variety of SPA sources and ­treatments have been used in FeLV-infected cats. In some studies a high rate of tumor remission and conversion to

1282

Section  XIII  Infectious Diseases

FeLV-­negative status was observed; in others responses were less dramatic and short lived. However, in an experimental study that included kittens with experimental FeLV infection, SPA treatment neither reversed anemia nor improved humoral immune function. In a placebo-­controlled study, treatment of ill client-owned FeLV-infected cats with SPA (10 mcg/kg twice weekly for up to 10 weeks) did not cause a statistically significant difference in FeLV status, survival time, or clinical and hematologic parameters when compared with a placebo-treated control group; but it did result in significant improvement in the owners’ subjective impression of the health of their pets (McCaw et al., 2001). Propionibacterium acnes, formerly Corynebacterium ­parvum, is a killed bacterial product that stimulates macrophages and the release of various cytokines and interferons and enhances T cell and natural killer cell activity in mice. It has been used in FeLV-infected cats (0.2 mg/cat intravenously [IV] twice a week and then once a week for at least 6 weeks), but no prospective studies have been performed, and anecdotal reports note that about 50% of the treated cats improved. A number of other immunostimulants, including a cell wall extract of a nonpathogenic strain of Mycobacterium bovis (Bacille Calmette-Guérin), extracts of Serratia marcescens, levamisole, and diethylcarbamazine, have not shown any efficacy in altering virus production or immune function in properly performed (controlled) studies despite in vitro evidence of immunomodulatory effects.

Antiviral Chemotherapy Most antivirals used in cats are licensed for humans and are intended specifically for treatment of HIV infection. Some can be used to treat FIV infection because most enzymes of FIV and HIV have similar sensitivities to various inhibitors. However, few controlled studies have been performed to support their use in cats. Nucleoside analogs are usually less effective against FeLV when compared to FIV because FeLV is not as closely related to HIV. Zidovudine, 3′-azido-2′,3′-dideoxythymidine (AZT), is a nucleoside analog (thymidine derivative) that blocks the reverse transcriptase of retroviruses and inhibits new infections of cells. AZT can inhibit FIV replication in vitro and in vivo, reduce plasma virus load, improve the immunologic and clinical status of FIV-infected cats, increase quality of life, and prolongs life expectancy. In a placebo-controlled trial, AZT improved stomatitis in naturally infected cats. It should be used at a dosage of 5 to 10 mg/kg every 12 hours orally or subcutaneously. The higher dose should be used carefully since side effects can develop. For subcutaneous injection the lyophilized product should be diluted in isotonic NaCl solution to prevent local irritation. For oral application syrup or gelatin capsules (with dosage individualized for the cat) can be used. During treatment a CBC should be performed regularly (weekly for the first month) because nonregenerative anemia is a common side effect, especially if the higher dosage is used. If blood values are stable after the first month, a monthly check is sufficient. Cats with bone marrow suppression should not be treated with AZT. Studies in which FIV-infected cats were treated for 2 years showed that AZT is well tolerated. Some cats may develop a mild decrease of hematocrit initially in the first 3 weeks that resolves

even if treatment is continued. If hematocrit drops below 20%, discontinuation is recommended, and anemia usually resolves within a few days. Unfortunately, as in HIV, AZT-resistant mutants of FIV can arise as early as 6 months after initiation of treatment. AZT is also effective against FeLV in vitro. When treated less than 1 week after experimental inoculation, cats were protected from FeLV bone marrow infection and persistent viremia. However, in a study with naturally FeLV-infected cats, 6 weeks of treatment with AZT did not lead to a statistically significant improvement of clinical, laboratory, immunologic, or virologic parameters. In general, therapeutic efficacy of AZT in FeLV-infected cats seems to be less promising than in cats infected with FIV. It should be used only at low dosage (5 mg/kg orally [PO] or SQ q12h) in FeLV-infected cats because of its bone marrow–suppressive effects. Several other nucleoside analogs with a similar mode of action to that of AZT and licensed for treatment of HIVinfected patients have activity against feline retroviruses. The in vitro and in vivo activity of these drugs against FIV and FeLV is summarized in Table 286-1. Foscarnet is a pyrophosphate analog that reversibly inhibits virus-specific deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) polymerase and reverse transcriptase by binding to the enzymes at a site distinct from that of nucleoside analogs. It has a wide spectrum of activity against DNA and RNA viruses. In vitro foscarnet has activity against FIV and FeLV, but no reliable data exist on its in vivo efficacy in cats, and its use in cats is limited because of toxicity. It is nephrotoxic and myelosuppressive and chelates cations such as calcium, so that ­hypocalcemia, hypomagnesemia, and hypokalemia may develop. Foscarnet is toxic to epithelial cells and mucous membranes, leading to severe gastrointestinal side effects and ulceration of genital epithelium. Suramin, a sulfated naphthylamine, has been used primarily as an antiparasitic. It is also effective against several viruses through inhibition of reverse transcriptase by interacting with the template-primer binding site of the enzyme that is necessary for DNA prolongation. However, it is also associated with severe side effects, including nausea and anaphylactic shock (during administration), peripheral neuritis, agranulocytosis, hemolytic anemia, and destruction of the adrenal cortex. No reliable studies exist to show its effect against FIV. Suramin was used to treat FeLV-infected cats, although only a limited number of cats were studied. FeLV-related anemia improved in these cats, and serum viral infectivity ceased transiently. However, because these studies were not controlled, results must be interpreted carefully, and the severe side effects limit its use in cat patients. T20 is a new anti-HIV drug that inhibits virus entry by inhibiting fusion of the virus with the cell membrane. It has been tested against several retroviruses, including FIV, but showed minimal antiviral effect likely because of insufficient sequence homology of the primary amino acid sequence of HIV and FIV in the critical regions. It has not been tested against FeLV but is likely ineffective. AMD3100 belongs to the new class of bicyclams that act as selective antagonists of the chemokine receptor CXCR4. CXCR4 is the main coreceptor for T cell–line-adapted HIV strains, and blocking the CXCR4 receptor leads to inhibition of virus entry. FIV also uses CXCR4 for virus entry,



Chapter  281  Feline Leukemia Virus and Feline Immunodeficiency Virus

and a high degree of homology exists between the human and feline CXCR4. AMD3100 is not licensed as an antiviral compound but as a stem cell activator for patients that undergo bone marrow transplantation. It is effective against FIV in vitro; and in a placebo-controlled doubleblind study in which 40 naturally FIV-infected cats were treated with AMD 3100 (0.5 mg/kg q12h SQ for 6 weeks) it caused a statistically significant improvement in clinical signs and decreased the proviral load in FIV-infected cats without side effects. AMD3100 has not been tested against FeLV but is likely ineffective because FeLV uses ­different receptors for virus entry into the cell. Lactoferrin is a mammalian iron-binding glycoprotein that has antibacterial, antifungal, antiprotozoal, and antiviral properties. Antiviral activity may occur as a result of lactoferrin interaction with the viral receptors on the cell surface or by direct neutralization or inhibition of the viral particle. Lactoferrin is produced by mucosal epithelial cells of many mammalian species and is present in secretions such as tears, milk, saliva, seminal or vaginal fluids, and low concentrations in plasma. Side effects are not described. Lactoferrin had some effect in cats with stomatitis, and it may be an option for treatment of FIV- and FeLV-related stomatitis. Human interferon-α has immune-modulatory effects but also acts as a true antiviral compound by inducing a general antiviral state of cells that protects them against virus replication (also see Chapter 85). Two common treatment regimens are used in cats: subcutaneous injection of high-dose interferon (104 to106 units/kg q24h), or oral application of a low-dose treatment (1 to 50 units/kg q24h). Measurable serum levels can be obtained when given subcutaneously, but using this regimen it becomes ineffective after 3 to 7 weeks because of development of neutralizing antibodies. Human interferon-α given orally is not absorbed but is destroyed in the gastrointestinal tract; no measurable serum levels develop. The only way oral interferon may have an effect is by stimulation of the local lymphoid tissue in the oral cavity. In murine studies it was shown that subcutaneous administration of interferon-α had an antiviral effect, whereas oral administration only caused immunomodulation. In a recent study a positive effect on the survival of FIV-infected cats could be demonstrated using low-dose oral human interferon-α. Human interferon-α inhibits FeLV replication in vitro and has been used in several studies in FeLV-infected cats. Treatment with high dosages of subcutaneous human interferon-α (1.6 × 104 and 1.6 × 106 units/kg SQ) in experimentally FeLV-infected cats with high levels of persistent antigenemia resulted in significant decreases in circulating FeLV p27 antigen. However, as a result of anti-interferon-α antibody development, cats became refractory to therapy after 3 or 7 weeks. In a study of naturally FeLV-infected cats, high-dose subcutaneous treatment with human interferon-α (1 × 105 units/kg SQ q24h for 6 weeks) did not lead to a statistically significant improvement of clinical, laboratory, immunologic, or virologic parameters. In an experimental placebo-­controlled study, low-dose oral interferon-α (0.5 units/cat or 5 units/cat PO) did not lead to a difference in the ­development of viremia when treatment started directly after challenge, although treated cats had significantly fewer clinical signs and longer survival times when compared to the placebo group (with a

1283

better response using 0.5 units/cat). In a recent placebocontrolled study including ill client-owned FeLV-infected cats that were treated with low-dose oral interferon-α (30 units/cat q24h for 7 consecutive days on a 1-week-on/1week-off schedule), there were no ­statistically significant differences in FeLV status, survival time, clinical or hematologic parameters or subjective improvement in the owners’ impression of clinical signs. Feline interferon-ω recently was licensed for use in veterinary medicine in some European countries and Japan. Interferons are species-specific; therefore feline interferon-ω can be used for prolonged periods without antibody development. No side effects have been reported in cats. Feline interferon-ω is active against FIV in vitro, but to date only one study has been performed in field cats, and the study did not show significant changes in survival rate when compared to a placebo group. Feline interferon-ω also inhibits FeLV replication in vitro. In a placebo-­controlled field study, 48 cats with FeLV infection were treated with interferon-ω (106 units/kg SQ q24h on 5 consecutive days repeated three times with several weeks between treatments). A statistically significant difference was found in the survival time of treated versus untreated cats (De Mari et al., 2004). However, no virologic parameters were measured during the study to support the hypothesis that the interferon actually had an anti-FeLV effect rather than an inhibition of secondary infections, and further studies are needed. A summary of reported experimental treatments is found in Table 286-1.

References and Suggested Reading Arai M et al: The use of human hematopoietic growth factors (rhGM-CSF and rhEPO) as a supportive therapy for FIV-infected cats, Vet Immunol Immunopathol 77:71, 2000. De Mari K et al: Therapeutic effects of recombinant feline interferon-omega on feline leukemia virus (FeLV)–infected and FeLV/feline immunodeficiency virus (FIV)–coinfected symptomatic cats, J Vet Intern Med 18:477, 2004. Hartmann K: Feline leukemia virus infection. In Greene CE, ­editor: Infectious diseases of the dog and cat, St Louis, 2006a, Elsevier Saunders, p 105. Hartmann K: Antiviral and immunomodulatory chemotherapy. In Greene CE, editor: Infectious diseases of the dog and cat, St, Louis, 2006b, Elsevier Saunders, p 10. Hartmann K et al: Treatment of feline leukemia virus-infected cats with paramunity inducer, Vet Immunol Immunopathol 65:267, 1998. Hartmann K, Donath A, Kraft W: AZT in the treatment of feline immunodeficiency virus infection, Feline Pract 5:16; 6:13, 1995. Levy JK: CVT update: feline immunodeficiency virus. In Bonagura JD, editor: Kirk’s current veterinary therapy XIII small animal practice, Philadelphia, 2000, Saunders, p 284. Levy J et al: 2001 Report of the American Association of Feline Practitioners and Academy of Feline Medicine Advisory Panel on feline retrovirus testing and management, J Feline Med Surg 5:3, 2003. McCaw DL et al: Immunomodulation therapy for feline leukemia virus infection, J Am Anim Hosp Assoc 37:356, 2001. Sellon RK, Hartmann K: Feline immunodeficiency virus ­infection. In Greene CE, editor: Infectious diseases of the dog and cat, St Louis, 2006, Elsevier Saunders, p 131. Sheets MA et al: Studies of the effect of acemannan on retrovirus infections: clinical stabilization of feline virus–infected cats, Mol Biother 3:41, 1991.

C hapter  

282

Feline Calicivirus Infection Jane E. Sykes, Davis, California

F

eline calicivirus (FCV) is a common cause of feline upper respiratory tract disease (URTD), accounting for anywhere between 20% and 53% of cases. Infection may be manifested by fever, conjunctivitis, rhinitis, oral ulcerations, and/or chronic stomatitis, although occasionally skin ulcerations, lameness, and pneumonia may occur. The severity and signs of illness depend on the strain of FCV involved, the infecting dose, and the degree of host immunity. FCV is a nonenveloped, single-stranded ribonucleic acid (RNA) virus with a spheric capsid studded with cupshaped depressions. Like other RNA viruses, the genome of FCV continually undergoes rapid mutation with minimal rates of repair, increasing the diversity of strains over time. Cats that recover from URTD may develop a persistent oropharyngeal infection with continuous shedding of virus from this site, although the magnitude of shedding varies over time and among individual cats. In many cats shedding terminates weeks to months after infection, but in a few cats shedding is lifelong. Some cats appear never to shed virus. Because of the carrier state, the prevalence of FCV infection in the general cat population is high, ranging from 8% to 47%, depending on the density of the cat population sampled. A single cat may be infected with multiple variants of FCV at the same time, each derived from the original infecting strain as a result of genetic mutation, drift, and selection pressures (Radford et al., 1998). URTD caused by FCV is a problem especially in cats residing in multiple-cat households and breeding and boarding catteries. Although the introduction of vaccines targeting FCV in the mid 1970s may have reduced the severity of clinical signs, the vaccines do not prevent infection or persistent shedding of FCV, and outbreaks of URTD still occur, even in well-vaccinated cat populations. Vaccine virus itself may be shed from the oropharynx, and virus closely related to the F9 vaccine strain has been detected in cat colonies that are chronically shedding FCV. There has been some concern that vaccine pressure may have led to selection of FCV strains that have poor cross-reactivity with the vaccine strain F9, and incorporation of additional strains into vaccines has been proposed (Dawson et al., 1993). Over the last 5 years several highly virulent strains of FCV have been isolated from outbreaks of a systemic, febrile illness in North American cats. This condition was described initially in northern California (Pedersen et al., 2000) and subsequently in several other American states (Rong et al., 2006). Most recently it has been described in the United Kingdom (Coyne et al., 2006). The disease has 1284

been termed FCV-associated virulent systemic disease (VSD), and in some outbreaks has been associated with mortalities of up to 67%. Furthermore, vaccination with currently available FCV vaccines apparently has not been protective. The purpose of this chapter is to discuss the clinical signs, epidemiology, diagnosis, control, and treatment of FCV infections, with particular emphasis on the recently reported outbreaks of VSD.

Epidemiology Infection with FCV may be acquired by direct contact with an acutely infected cat, organisms persisting within the environment, or a carrier cat. FCV is shed primarily in oral, nasal, and ocular secretions and can also be found in blood, urine, and feces of infected cats. Transmission over distances of about 4 feet may occur via droplets generated by sneezing cats. FCV-associated VSD was first described in northern California in 1998 (Pedersen et al., 2000). Death occurred in 33% to 50% of infected cats, and this strain was highly contagious, spreading via contaminated fomites despite implementation of aggressive disinfection measures. A novel FCV strain, FCV-Ari, was isolated from affected cats. Laboratory cats experimentally infected with FCVAri developed a disease syndrome identical to that seen in naturally infected cats. Since FCV-Ari was described, at least five additional outbreaks have been recognized in Pennsylvania, Massachusetts, Tennessee, Nevada, and southern California; and in 2003 an outbreak of systemic caliciviral disease occurred in Staffordshire, England (Coyne et al., 2006). FCV-Kaos, a genetically distinct strain from FCV-Ari, was isolated from cats in the southern California outbreak (Hurley et al., 2004), and the strains isolated in the Massachusetts (FCV-Diva) and United Kingdom (UKOS) outbreaks also have been genetically distinct. This may suggest that the mutation(s) associated with VSD are different in each case or that these mutations occurred in a part of the FCV genome that was not sequenced. In the majority of outbreaks a hospitalized shelter cat appeared to be the source of infection. Three outbreaks involved a single veterinary hospital, one spread to a veterinary research facility in the course of the outbreak investigation, and the largest reported outbreak affected 54 cats in three veterinary practices and a rescue group in the west Los Angeles area from June to August, 2002 (Hurley et al., 2004). The spread of this southern California outbreak was attributed to the travel of clients and staff between multiple practices located within a 1-mile radius. With the exception of the United Kingdom

outbreak, which involved two neighboring households, spread of disease was limited to the affected clinic(s) or shelter, with no spread within the community reported. Otherwise healthy, adult, vaccinated cats were affected predominantly, whereas kittens tended to show less severe signs. In all cases the outbreaks resolved within approximately 2 months. Two outbreaks occurred in the spring, three in the summer, and two in the fall. No outbreak has yet been reported in winter, a time when the kitten population is lowest, reflecting the possible role of kittens in the generation and transmission of virulent FCV strains. Transmission of the virulent FCV strains occurs readily through fomite transmission via veterinary hospital staff and pet owners, by movement of clinically and subclinically infected cats between clinics and private homes, and by indirect contact of outpatients with subclinically infected inpatients. An epidemiologic analysis of the outbreak that occurred in southern California showed that adult cats (>1 year old) were at significantly higher risk than kittens (90%). Positive culture results were also obtained on serum samples from acutely ill cats, although the sensitivity was lower than with culture from oropharyngeal swabs. Sensitivity of viral culture on oropharyngeal swabs decreases rapidly in recovering cats, and a single negative swab taken more than a week after onset of clinical signs does not rule out infection with FCV. At least two to three negative cultures should be obtained at weekly intervals before concluding that virus shedding is likely to have terminated. In general, serology is not recommended for routine diagnosis of FCV infections. Because of widespread exposure to FCV, acute and convalescent phase samples are required to demonstrate recent infection. Titers induced by vaccination can confound diagnosis; and, because of the large numbers of FCV strains, titers may vary, depending on the degree of homology between the infecting virus and the FCV strain used in the assay. Nevertheless, in the case of FCV strains causing VSD, serology using virus neutralization has been sensitive and specific and was useful for investigation and control of the southern California outbreak (Hurley et al., 2004). There was no cross-neutralization between the vaccine (F9) strain and FCV-Kaos or FCV-Ari; thus identification of unexposed cats even in the

face of recent vaccination may be possible. Whether this will be true for other hypervirulent strains (and thus for other outbreaks) awaits further investigation. Amplification of FCV nucleic acid using the reversetranscriptase polymerase chain reaction (RT-PCR) represents another diagnostic assay that may be considered for diagnosis. Compared with those for deoxyribonucleic acid viruses such as feline herpesvirus 1, PCR-based assays for FCV are less reliable because of the difficulty in designing assays that amplify nucleic acid from a variety of different strains and the susceptibility of viral RNA to rapid degradation by RNase enzymes in the environment. Falsepositive results associated with contamination can occur during sample collection or in the laboratory. Current PCR-based assays for FCV are generally only available in research laboratories, and quality control may vary from laboratory to laboratory and even between individual staff members working in the same laboratory. Therefore the results of PCR-based testing should be interpreted with caution. In the southern California outbreak of VSD, all isolates recovered in culture were successfully amplified using RT-PCR (Hurley et al., 2004). Regardless of the method used to detect FCV infection, the results of diagnostic testing should always be interpreted in the light of clinical signs because asymptomatic cats may shed FCV. The same applies for FCV strains associated with VSD; because there have been no consistent molecular differences identified between highly virulent strains and other strains of FCV, it is not possible to identify an isolate as a VSD strain using molecular typing methods. Positive identification of an outbreak requires that a molecularly distinct strain of FCV be isolated and sequenced from at least two affected cats in association with the appearance of consistent clinical signs. Once an outbreak has been identified in this manner, nucleic acid sequencing may be useful for determining whether additional FCV isolates obtained in the outbreak have the potential to cause VSD (because of their relation to the original isolates) or whether they represent unrelated field FCV or vaccine strains. Because subclinically infected cats are capable of transmitting VSD, all exposed cats, whether symptomatic or not, should be checked by viral culture or RT-PCR before being introduced to naïve cats.

Treatment Treatment of disease resulting from FCV infection is symptomatic. Broad-spectrum antimicrobials (e.g., amoxicillin, 22 mg/kg orally [PO] q12h; or doxycycline, 10 mg/kg PO q24h) may be required to counteract secondary bacterial infection. Fluid and nutritional support is essential in severe cases, and airway humidification should also be considered. Placement of esophagostomy or gastrostomy tubes allows enteral nutrition of cats with inappetence. Oxygen may be required for cats with pneumonia. In addition to the treatments described in the previous paragraph, cats with VSD should be placed in isolation and treated aggressively with colloid-containing fluids such as Hetastarch (Hespan, Baxter; Deerfield, IL). A variety of different treatments have been tried, including a wide range of broad-spectrum antibiotics and oral interferon-α. Glucocorticoids at immunosuppressive doses

(1 mg/kg PO q12h) have also been used. In the outbreak in southern California five severely affected cats were treated with dexamethasone (in addition to other supportive treatments) and survived; one cat that was treated with prednisone died, but the remaining cats that died did not receive glucocorticoids (Hurley and Sykes, 2003). One cat in the northern California outbreak lived ­following glucocorticoid treatment; the remainder were not treated with steroids.

Recommendations for Control Although outbreaks can be devastating within an affected clinic or shelter, VSD remains extremely uncommon. Quick recognition and implementation of effective control measures, including proper disinfection, quarantine, and testing procedures, will further reduce the impact of this disease. Recognizing that VSD may be spread even by mildly symptomatic cats (especially kittens), veterinarians should exercise careful infectious disease control whenever dealing with a cat with URTD. FCV is reliably inactivated by sodium hypochlorite (in the absence of organic matter and with adequate contact time) but not by other compounds commonly used for disinfection in veterinary hospitals such as chlorhexidine or quaternary ammonium compounds. Therefore routine decontamination after exposure to a cat with upper respiratory infection should be to clean with a detergent solution and then disinfect with 5% sodium hypochlorite diluted with water to 1:32 (½ cup of 5% bleach per gallon of water). In the absence of effective disinfection, FCVs reportedly can persist in a dried state at room temperature (20° C) for up to 28 days (Doultree et al., 1999). Therefore effective cleaning and quarantine are crucial. Specific control measures recommended when VSD is diagnosed or strongly suspected include strict isolation of suspect cases, isolation of exposed cats for at least 2 weeks after exposure, ensuring that exposed or infected

Chapter  282  Feline Calicivirus Infection

1287

cats are not shedding virus before release into environments containing naïve cats, and thorough disinfection with 5% bleach solution or heat sterilization. Carpeted areas/homes should be steam cleaned and closed to cats for a minimum of 4 weeks. Clinics in which disease continues to spread despite instituting these precautions should consider closing to cat admissions for 1 to 2 weeks. If recently vaccinated cats are less severely affected in any outbreak, vaccination of naïve cats with a modified-live vaccine at least 1 to 2 weeks before potential exposure may be helpful, although it should be recognized that vaccination with a modified-live vaccine may result in positive test results using virus isolation.

References and Suggested Reading Coyne KP et al: Lethal outbreak of disease associated with feline calicivirus infection in cats, Vet Rec 158(16):544, 2006. Dawson S et al: Typing of feline calicivirus isolates from different clinical groups by virus neutralisation tests, Vet Rec 133(1):13, 1993. Doultree JC et al: Inactivation of feline calicivirus, a Norwalk virus surrogate, J Hosp Infect 41(1):51, 1999. Hurley K, Sykes JE: Update on feline calicivirus: new trends, Vet Clin North Am Small Anim Pract 33(4):759, 2003. Hurley K et al: An outbreak of virulent systemic feline calicivirus disease, J Am Vet Med Assoc 224(2):241, 2004. Pedersen NC et al: An isolated epizootic of hemorrhagic-like fever in cats caused by a novel and highly virulent strain of feline calicivirus, Vet Microbiol 73(4):281, 2000. Pesavento PA et al: Pathologic, immunohistochemical, and electron microscopic findings in naturally occurring virulent systemic feline calicivirus infection in cats, Vet Pathol 41(3):257, 2004. Radford AD et al: Quasispecies evolution of a hypervariable region of the feline calicivirus capsid gene in cell culture and in persistently infected cats, J Gen Virol 79(pt 1):1, 1998. Rong S et al: Characterization of a highly virulent feline calicivirus and attenuation of this virus, Virus Res 122(1-2):95, 2006.

C hapter  

283

Babesiosis Adam J. Birkenheuer, Raleigh, North Carolina

O

ne of the earliest descriptions of intraerythrocytic parasites in dogs with signs consistent with babesiosis was made in 1896, and the first documented case of canine babesiosis in the United States was reported in 1934. Initially there were only two species of Babesia believed to infect dogs; however, at the time of this writing, there are at least nine genetically unique piroplasma that have been identified in the blood of dogs (Table 283-1).

Epizootiology Piroplasma are intraerythrocytic protozoan parasites of the phylum Apicomplexa that are frequently transmitted by ticks. Piroplasma include organisms in the families Babesiidae and Theileridae. Babesia spp. are distinguished from Theileria spp. by the absence of any preerythrocytic stage in the mammalian host. In contrast, Theileria spp. first infect leukocytes (typically lymphocytes) before the organisms infect erythrocytes. Babesiosis was the first documented tick-transmitted infection, demonstrated by Smith and Kilbourne in 1888. They demonstrated that “Texas fever” was transmitted by ticks in cattle and that the causative agent was believed to be either Babesia bigemina or Babesia bovis. Over 100 species of Babesia have since been described, and with the advent of molecular techniques such as the polymerase chain reaction (PCR) many new species and genotypes are identified each year. Although many vertebrate species can be infected with two or more of the known Babesia spp., this chapter focuses on canine piroplasmosis.

Transmission and Risk Factors The primary route of transmission for piroplasma is believed to be via a tick vector. The known or suspected tick vectors for each piroplasma are listed in Table 283-1. The recent emergence of some piroplasma such as Babesia gibsoni is likely to be associated with nontick-associated routes of transmission. In North America the majority of B. gibsoni transmission appears to be among American pit bull terriers and is associated with transplacental infection and direct inoculation via dog bites. Cases of B. gibsoni in dogs that were not of this breed were frequently bitten by an American Pit Bull terrier or received a transfusion with blood donated by a dog of that breed. However, more B. gibsoni cases are being identified in other canine breeds within the United States, without these exposure to these known risk factors. Breed associations and risk factors for infection are listed in Table 283-1.

1288

Clinical Disease The disease manifestations of canine piroplasma infection are highly variable. Multiple factors are responsible for the differences in pathogenicity, including the genotype/species of piroplasm, individual host immune responses, and age and possibly breed of the host. Classic canine piroplasmosis is characterized by anemia, thrombocytopenia, hyperglobulinemia, fever that may wax and wane, and splenomegaly. These findings are fairly consistent in most cases regardless of geographic region, genotype of piroplasm, or host. Hemoglobinemia is a relatively rare finding in dogs in North America and is most commonly documented in dogs in South Africa. In at least one study 85% of dogs with piroplasmosis had Coombs’positive test results. Thus piroplasmosis should be considered as a differential diagnosis for all dogs presenting with immune-mediated hemolytic anemia (IMHA) and or thrombocytopenia. In highly endemic areas, for dogs with a history of known risk factors for piroplasmosis or for dogs of a breed known to be at high risk for piroplasmosis, empiric antiprotozoal therapy (see following paragraphs) should be started immediately after samples are obtained for specific testing. There are no pathognomonic biochemical or urinalysis findings in dogs with piroplasmosis. The most consistent biochemical findings include hyperglobulinemia and less commonly hyperbilirubinemia with mildly increased liver enzymes. Some dogs present for pigmenturia consisting most commonly of bilirubin and occasionally hemoglobin. There are recognized differences in the virulence of the different species/genotypes of piroplasms that infect dogs (see Table 283-1). Babesia canis rossi, which has only been documented in southern Africa, is considered highly virulent and has been associated with severe disease manifestations such as disseminated intravascular coagulation, central nervous system signs and hypoglycemia, and in some cases death. Babesia canis vogeli has a nearly worldwide distribution and is typically considered the least virulent. Babesia canis canis is considered to have virulence intermediate to B. canis rossi and B. canis vogeli and is recognized primarily in Europe, with the majority of cases having been reported in France. B. gibsoni is a small piroplasm (1 to 3 μm) that is rapidly emerging and seems to now have a nearly worldwide distribution. B. gibsoni is considered a moderately virulent piroplasma. A Babesia microti–like parasite, formerly referred to as Theileria annae, has been recently recognized in Spain. In addition to the classic signs associated with piroplasmosis, this organism has been associated with renal failure and proteinuria,

Chapter  283  Babesiosis



1289

Table 283-1 Overview of Canine Piroplasmosis Genotype/Species

Distribution

Vector

Risk Factors

Virulence

Babesia canis vogeli

Worldwide

Rhipicephalus sanguineus

Babesia canis rossi

South Africa

Haemaphysalis leachi

Greyhounds, ticks, blood transfusion Ticks

+++

Babesia canis canis

Europe

Dermacentor reticulates

Ticks

++

Babesia gibsoni

Worldwide

Haemaphysalis spp., others?

American pit bull terriers, dog bites, ticks, blood transfusion

++

Babesia microti-like (Theileria annae) Babesia conradae

Spain

Ixodes hexagonus?

Ticks

+++

California

?

?

+++

Babesia spp. (UK)

?

?

++?

Babesia spp. (Coco)

United Kingdom only? United States only?

?

Neoplasia, splenectomy

+?

Theileria equi

Europe only?

?

?

?

+

Treatment

Parasite Clearance With Treatment

Imidocarb dipropioY nate (6.6 mg/kg IM q2 weeks) Imidocarb dipropioY nate (6.6 mg/kg IM q2 weeks) Imidocarb dipropioY nate (6.6 mg/kg IM q2 weeks) Atovaquone (13.3 mg/ Likely in 85% kg PO TID w/ a of cases fatty meal) and Azithromycin (10 mg/kg PO q24h) simultaneously for 10 days ? ? ? Atovaquone (13.3 mg/kg PO TID w/ a fatty meal) and azithromycin (10 mg/kg PO q24h) simultaneously for 10 days? ? Imidocarb dipropionate (6.6 mg/kg IM q2 weeks) ?

?

? Likely

?

IM, Intramuscularly; PO, orally; TID, three times a day; Y, yes; ?, unknown or not studied; +, mild; ++, moderate; +++, severe.

presumably caused by glomerular disease. Babesia conradae, originally believed to be B. gibsoni, is a highly virulent parasite and is associated with high mortality rates. It is important to note that all species have caused severe disease manifestations in individual patients; thus the guidelines for virulence may not be strictly clinically relevant. However, it is important that the clinician accurately identify the species/genotype infecting the individual patient because the prognosis and treatment for each ­species can vary. “Atypical” presentations of canine piroplasma infection appear to be becoming more common. The most common atypical presentations include thrombocytopenia and hyperglobulinemia without anemia, thrombocytopenia alone, hyperglobulinemia alone, and the complete absence of hematologic or biochemical abnormalities. The reasons behind these atypical presentations are not clearly understood, but possible causes include parasite adaptations to canine hosts resulting in decreased virulence, increased clinician vigilance and willingness to test, spontaneous recovery, and alternative routes of

transmission that may be associated with decreased virulence (direct inoculation or transplacental transmission).

Diagnosis The diagnosis of piroplasmosis in the clinical setting can be quite challenging. Several factors can increase the clinician’s index of suspicion such as breed (greyhounds have increased prevalence of B. canis vogeli, and American Pit Bull terriers have increased prevalence of B. gibsoni infections), history of a dog bite, blood transfusion, or tick attachment. Three basic methods are available to diagnose piroplasmosis: light microscopy, serology, and nucleic acid–based detection methods. Unfortunately the clinical sensitivity and specificity of most of the available tests are unknown; but clinical experience, case series and reports, and limited studies performed on experimentally infected dogs have demonstrated that all modalities can have either false-positive or false-negative results. When performed by an experienced reader, light microscopy is highly specific for the presence of piroplasmosis,

1290

Section  XIII  Infectious Diseases

but, because of the relatively low limit of detection (0.001% parasitemias), the sensitivity is poor; thus it is not recommended as a sole screening test. In addition, several species/genotypes are virtually indistinguishable by light microscopy, making accurate identification to the species/genotype level nearly impossible. Serologic detection of antipiroplasma antibodies, which is almost always performed in commercial laboratories by the use of indirect fluorescent antibody (IFA) assays, is considered to be fairly sensitive as a screening test. Since serology only provides indirect evidence of infection and is well documented to have false-negative results in some clinical cases, it is the responsibility of the clinician to interpret the results in light of the clinical presentation and the response to treatment. Despite the fact that IFA assays are available for several different genotypes, the ability of these assays to accurately differentiate the species/genotype actually causing a given infection is relatively poor (i.e., the highest titer does not always correlate to which species is present). It is for these reasons that nucleic acid based testing is quickly becoming an important component to the diagnosis of canine babesiosis. PCR assays are the primary molecular method used by commercial diagnostic laboratories. PCR is generally accepted to have increased sensitivity compared to light microscopy, and in some cases the limit of detection is 1300 times lower. The overall sensitivity of one assay for the diagnosis of chronic B. gibsoni infections was 90% over three different testing periods. The assay detected infection in 100% of studied dogs when two consecutive tests were performed. Although this improved sensitivity is important, it is the exquisite specificity of PCR (>99.9% when the proper controls are used) that give it outstanding clinical usefulness. A positive result from a reputable laboratory is consistent with infection and should identify the specific species/genotype so appropriate therapeutic decisions can be made. The major clinical concern for PCR assays is the lack of assay standardization among laboratories and the marked variability in sensitivity and specificity (differences of limits of detection ≥1000 fold) with different assay design, reaction protocols, controls, and reagents. Therefore it is critical that clinicians contact individual laboratories and get specific information about each assay and the controls used for proper interpretation of test results. Ultimately in some cases a multifaceted approach that includes microscopy, serology, and PCR may be necessary to maximize the chances of diagnosing piroplasma infections.

Treatment and Prevention Significant improvements in the availability and types of treatments for canine babesiosis have been made. In highly endemic areas or in breeds with increased risk of infection, therapy should be started as soon as possible and is often administered empirically based on clinical suspicion. Specific therapies for canine piroplasmosis are presented in Table 283-1. Based on our clinical experience, treatment with atovaquone (Mepron, GlaxoSmithKline) and azithromycin is effective and capable of clearing B. canis vogeli infections but is

considerably more expensive than imidocarb dipropionate (Imizol, Schering-Plough). A combination formulation of atovaquone with proguanil hydrochloride (Malarone, GlaxoSmithKline) is less expensive, but it is poorly tolerated by dogs, with substantial vomiting as an adverse effect. Imidocarb and the less widely available diminazene aceturate are both capable of inducing remission of clinical signs in dogs with B. gibsoni infection, but neither treatment is successful at clearing the infection. Their use in B. gibsoni infections is warranted when atovaquone and azithromycin are unavailable or the cost of treatment is prohibitive. The clinical signs associated with piroplasmosis typically begin to improve within 1 week of beginning specific therapy. If patients are not responding to specific therapy, secondary treatments should be administered, or alternative diagnoses should be considered. Since the anemia and thrombocytopenia associated with piroplasmosis are often immune mediated, immunosuppressive therapy is frequently considered as an adjunctive therapy. If piroplasmosis is highly suspected or definitively identified, I recommend only supportive care and antiprotozoal therapy. It is my experience that prolonged immunosuppressive therapy (i.e., weeks to months) or splenectomy before treatment with specific antiprotozoal drugs substantially reduces the ability to clear the parasitemias and subsequently is associated with a worse prognosis because of relapsing disease. In addition, many dogs with secondary IMHA and immune mediated thrombocytopenia purpura have responded to antiprotozoal drugs alone and have not required additional treatments. Clinical signs should resolve in most cases within 5 to 7 days of beginning antiprotozoal treatment. If immunosuppressive treatment must be instituted, prednisone alone (2 mg/kg/day) is usually sufficient and can be tapered more quickly (every 2 weeks versus every 3 to 4 weeks) compared to protocols for the treatment of idiopathic IMHA. Follow-up testing should consist of at least two consecutive negative PCR tests approximately 30 days apart. The best approach to the prevention of piroplasmosis has not been established, but several logical strategies have been proposed. In France a vaccine composed of an adjuvant and soluble antigens collected from supernatants of B. canis cultures is available. This vaccine induces partial protection (i.e., less severe clinical disease) but does not prevent infection and has only been demonstrated to be efficacious against B. canis. The avoidance of risk factors (see Table 283-1) is likely to result in reduced infection rates. The use of topical acaricides is likely to result in reduced infection rates, assuming that the agents either repel ticks or actually block the transmission. To date there are no data evaluating the efficacy of topical acaricides for the prevention of piroplasmosis, but their use in highly endemic areas is probably warranted based at least on the theoretic advantages. Finally, blood donors should be screened aggressively for the presence of piroplasma infections before their entry into a donor program and periodically if they have potentially been infected between screening and donation (e.g., ticks, volunteer donors that are indoor/outdoor).

Chapter  284  Canine Influenza



Suggested Reading Birkenheuer AJ et al: Geographic distribution of babesiosis among dogs in the United States and association with dog bites: 150 cases (2000-2003), J Am Vet Med Assoc 227:942, 2005. Birkenheuer AJ, Levy MG, Breitschwerdt EB: Efficacy of combined atovaquone and azithromycin for therapy of chronic Babesia gibsoni (Asian genotype) infections in dogs, J Vet Intern Med18:494, 2004.

C hapter  

1291

Boozer AL, Macintire DK: Canine babesiosis, Vet Clin North Am Small Anim Pract 33:885, 2003. Bourdoiseau G: Canine babesiosis in France, Vet Parasitol 138:118, 2006. Jacobson LS: The South African form of severe and complicated canine babesiosis: clinical advances 1994-2004, Vet Parasitol 138:126, 2006.

284

Canine Influenza Gabriele A. Landolt, Fort Collins, Colorado Katharine F. Lunn, Fort Collins, Colorado

I

nfluenza is a well-known and highly contagious disease that has burdened humans, poultry, horses, and pigs since ancient times. Before 2004 dogs were not commonly regarded as hosts for influenza A viruses. Since then canine influenza has been recognized as a recently emerged respiratory pathogen in dogs in the United States. First isolated from racing greyhounds in Florida, the virus has since spilled over into the nongreyhound dog population and has caused outbreaks of respiratory disease throughout the United States.

Etiology Canine influenza is primarily a respiratory disease caused by an influenza A virus. Influenza A viruses are members of the family Orthomyxoviridae and are enveloped viruses with segmented, single-stranded, negative-sense ribonucleic acid genomes. Based on antigenic properties of the two major envelope glycoproteins, hemagglutinin (HA) and neuraminidase (NA), influenza A viruses are further classified into 16 HA (H1-H16) and 9 NA (N1-N9) subtypes. The viruses exhibit only partial restriction of their host range, and occasionally influenza viruses or their genes are transferred between species. Undoubtedly the most prominent examples of direct transmission of influenza viruses among species are the recent infections of humans and cats with the highly pathogenic avian H5N1 viruses (“bird flu”). Yet, although cross-species transmission of influenza viruses may occur relatively frequently, these transmission events tend to be self-­limiting; and the

newly introduced viruses are only rarely maintained in the new host species. One of the few notable exceptions to this scenario is the recent transmission of an equine­lineage H3N8 virus to dogs in the United States, with apparent maintenance of the virus within the dog population. In the spring of 2004, 22 racing greyhounds housed at a training facility in Florida suffered from a severe respiratory illness that was characterized by cough and high fever. Eight of the affected dogs died from hemorrhagic pneumonia, and influenza A virus was recovered from the lung tissue of one animal. Sequence analysis of the viral genome revealed that the canine isolate was closely related to, and had evolved from, a contemporary equine H3N8 influenza virus. Over the course of that same year, outbreaks of influenza occurred at 14 greyhound racetracks in six states, and by 2005 the virus had spilled over into the nongreyhound dog population. Recent reports from researchers in the United Kingdom provide data supporting two additional independent incidents in which equine influenza viruses have been transmitted to dogs. When alerted to the canine influenza outbreak in the United States, researchers in the United Kingdom reanalyzed outbreaks of respiratory illness in foxhounds that had occurred in 2002 and 2003 and found evidence indicating that two distinct strains of equine influenza were the causative agents. Yet, in contrast to the apparent maintenance of the virus in the canine population in the United States, both equine-to-canine transmission events in the United Kingdom appear to have been self-limiting.

1292

Section  XIII  Infectious Diseases

Epidemiology and Disease Transmission Canine influenza virus infection has as of now been documented in the United States in at least 26 states and the District of Columbia. Because this disease has recently emerged in the dog population, there is little natural immunity to influenza virus infection; and all dogs are potentially susceptible, regardless of age, breed, sex, or vaccination status. Disease is most likely to occur in dogs that are housed in groups (e.g., in shelters, boarding or breeding kennels, canine day-care centers, or veterinary clinics). When canine influenza virus is introduced to a group of susceptible dogs, infection spreads rapidly, usually resulting in a significant outbreak of respiratory disease. These outbreaks are characterized by disease in all ages of dogs, regardless of vaccination status, with morbidity rates as high as 80% to 90%. Mortality rates are lower and most likely to be 5% or less. Canine influenza virus is shed in respiratory secretions and is highly contagious. Virus may be spread by direct dog-to-dog contact or by airborne transmission through droplets or aerosols generated by coughing or sneezing. It is likely that airborne spread of virus can occur over several feet, and the virus may survive for up to 48 hours in the environment. Fomites also play an important role in the transmission of canine influenza virus, with spread occurring through contact with infected bedding, feeding, or grooming equipment and even the clothing of personnel working with infected dogs. The time from exposure to canine influenza virus to onset of clinical signs is approximately 2 to 4 days. Viral shedding begins as soon as 2 days after exposure, peaks at 2 to 4 days, and may persist for 7 to 10 days. Thus dogs with canine influenza may shed virus before the development of clinical signs or very early in the course of disease. This has significant implications for both diagnosis and disease control. It is also important to note that infected dogs are unlikely to be shedding virus by 10 to 14 days after infection. There is no true carrier state for canine influenza virus infection; however, as many as 10% to 20% of infected dogs may shed virus with no apparent clinical signs. Therefore dogs that have been in contact with influenza suspects should also be regarded as potentially infectious to other dogs for 10 to 14 days after possible exposure.

Clinical Signs and Differential Diagnosis The most common clinical sign of canine influenza virus infection is a cough. The cough is typically soft and moist but may be harsh or dry. It may persist for several days or even weeks. Affected dogs may also have a serous or purulent nasal discharge. Fever may be noted in the early stages of infection and is usually transient. The signs of canine influenza virus infection are clinically indistinguishable from those of infection with other respiratory pathogens such as Bordetella bronchiseptica, adenovirus, or parainfluenza virus (See Chapter 147). However, when compared to kennel cough or more classic canine infectious tracheobronchitis, an outbreak of canine influenza typically

involves a much larger percentage of susceptible dogs, and disease is seen in animals that have been vaccinated against other respiratory pathogens. It is also important to remember that coinfections may occur with canine influenza virus and other kennel cough organisms. A small percentage of dogs exposed to canine influenza virus develop a more severe form of disease characterized by persistent fever, lethargy, dyspnea, and signs of bronchopneumonia. This form of the disease may be fatal; however, it is much less common than the milder form of disease and probably accounts for fewer than 10% of cases. The initial report of influenza virus infection in racing greyhounds described a peracute hemorrhagic pneumonia with a case fatality rate of 36%. Fortunately it appears that this is an uncommon manifestation of the disease in other dog populations.

Diagnosis The laboratory diagnosis of canine influenza is based on the culture of the etiologic agent (virus isolation), the demonstration of the viral nucleic acid (polymerase chain reaction [PCR}–based assays) or viral antigen in nasal or pharyngeal swab samples (e.g., detection of antigen by immunofluorescence, enzyme-linked immunosorbent assay [ELISA], or immunoperoxidase), or the detection of virus-specific antibodies (serology). Each of these methods has both merits and disadvantages; therefore it may be necessary to combine several diagnostic tools to identify canine influenza virus accurately and rapidly. Moreover, the timing of sample collection relative to the onset of clinical signs is critical in regard to appropriate test selection. For instance, virus shedding in nasal secretions is heaviest within the first few days after infection. Therefore nasal or pharyngeal swab samples submitted for virus isolation, nucleic acid, or antigen detection should be collected early in the course of disease (i.e., within the first 24 to 48 hours after onset of clinical signs). In contrast, since insufficient time has passed to allow for production of a detectable antibody response, serologic testing often may produce a negative result in the first few days after infection.

Virus Isolation Although virus isolation from clinical samples is critical for epidemiologic investigation and for future vaccine production, this technique may have limited value for diagnostic purposes. Virus isolation can take a minimum of 2 to 3 days; and the success of this technique for detection of infectious virus is influenced by virus strain, amount of viable virus present in the sample, and sample collection and storage techniques. Moreover, if the amount of virus shed is low, several serial passages may be required before sufficiently high viral titers are reached to allow detection using conventional hemagglutination assays. For sample collection, a short polyester-tipped swab should be used for the collection of secretions on the nasal mucosa. Cotton-tipped swabs should be avoided since influenza virus has been found to adhere to the cotton fibers, thus decreasing the chances of virus recovery. Optimally the swab should be placed in sterile

Chapter  284  Canine Influenza

viral transport medium (often available from a diagnostic laboratory) and kept on ice or refrigerated until further analysis.

Antigen Detection The most important advantages of diagnostic tests aimed at the detection of viral antigen over traditional virus isolation are the faster turnaround time and the ability to detect virions that have lost their infectivity. Immunofluorescence uses influenza-specific fluorochrome-labeled antibodies to detect virus-infected cells. The technique is highly sensitive and can be used to detect viral antigen in a broad range of clinical samples such as frozen tissue sections, tissue imprints, cells obtained from nasal scrapings, tracheal washes, and bronchoalveolar lavage fluid. Commercially available antigen-capture ELISA assays originally were developed for the rapid, onsite detection of human influenza A viruses (e.g., Flu OIA assay, Biostar; Directigen Flu-A assay, Becton Dickinson Microbiology Systems). The tests have been designed to detect the human influenza A virus nucleoprotein. Because the viral nucleoprotein is highly conserved among influenza A viruses of different subtypes and lineages, these assays have also been used to detect influenza infection in other species. For example, these rapid stall-side tests have been evaluated for the detection of influenza virus in horses and have been found to ­perform with high specificity and reasonable sensitivity. Similarly, recent studies conducted in dogs suggest that the ­commercial ELISA-based tests perform with a sensitivity similar to that of traditional virus isolation.

Polymerase-Chain Reaction–Based Assays Several diagnostic laboratories offer PCR-based tests (conventional and/or real-time PCR) for the diagnosis of canine influenza virus infection. PCR-based assays are extremely sensitive and theoretically can detect a single copy of the target nucleic acid in a sample. However, because of the high sensitivity of the assay, the greatest challenge facing the diagnostic application of PCR is the production of false-positive results. Nonetheless, PCR-based testing offers a more sensitive tool for the diagnosis of canine influenza than conventional techniques such as virus isolation or immunoassays. Real-time PCR assays are being used with increasing frequency in veterinary diagnostic laboratories. In contrast to conventional PCR methods, real-time PCR does not require post-PCR processing steps (e.g., gel electrophoresis and determination of fragment size) and therefore can generate results within 4 to 5 hours. By using a target-specific fluorescent probe, realtime PCR can also be used for quantification of virus and can be and has been used in routine diagnostic settings.

Antibody Detection Detection of virus-specific antibodies has been and continues to be an important tool in the diagnosis of canine influenza. Because most serologic assays are relatively easy to perform and cost-effective and large numbers of samples can be tested simultaneously, serologic testing is

1293

particularly useful in large-scale population surveillance. However, although it is useful, there are several limitations to serologic testing. Although the presence of antibody indicates exposure to antigen, it does not necessarily signify active infection or disease. Furthermore, antibody is not always detected in the presence of active infection. Experimental data obtained from dogs infected with canine influenza virus indicate that measurable antibody titers typically develop 7 or more days after infection. Therefore antibody may not be present during the first week of active infection, which is the period that is often most critical for disease management in settings where large numbers of dogs are housed together.

Therapy In the majority of affected dogs canine influenza is a selflimiting respiratory disease that does not require medical therapy. Secondary bacterial infections may complicate canine influenza and may manifest as purulent nasal discharge, persistent fever, or signs of pneumonia. These complications should be managed with antibiotic therapy. For dogs with bronchopneumonia, ideally antibiotic choices should be based on the results of culture and antibiotic sensitivity testing of samples obtained by ­transoral or transtracheal washes or bronchoalveolar lavage. If culture and sensitivity testing cannot be performed, broad-spectrum antibiotics that achieve adequate concentrations in the respiratory tract should be selected. Depending on the severity of the disease, dogs with pneumonia may also benefit from intravenous fluid therapy, nutritional support, oxygen therapy, nebulization, and coupage (Chapter 149). Antiviral drugs such as oseltamivir (Tamiflu, Roche) are not recommended in the management of canine influenza. The dose, duration, safety, and efficacy of this therapy are all currently unknown in dogs. In addition, these medications should be reserved as a vital defense for the protection of human health.

Disease Control Canine influenza should be considered in the differential diagnosis of any dog with acute cough, fever, or nasal discharge. This is particularly important if the dog has a recent history of exposure to other dogs such as at a canine day-care center, shelter, or boarding facility. Dogs that are considered to be influenza suspects should be separated from other dogs when presented to a veterinary clinic. Veterinary staff should wear a disposable gown, gloves, and shoe covers when working with influenza suspects; examination room surfaces and tables and any in-contact equipment should be disinfected when the patient leaves the hospital. If an influenza suspect requires hospitalization (e.g., for the management of pneumonia), the patient should be placed in an isolation facility to reduce the risk of disease transmission to other hospitalized patients. Again, disposable protective clothing should be worn when handling the patient, and care must be taken to avoid spread of virus by fomites. When determining the need for isolation of influenza suspects, it should be remembered that shedding of infectious virus

1294

Section  XIII  Infectious Diseases

ceases by 10 to14 days after infection and that exposed dogs may shed virus before the onset of clinical signs. If a dedicated isolation facility is not available in the veterinary hospital, strict barrier nursing precautions must be used in the management of hospitalized influenza suspects. These precautions include the use of dedicated or disposable protective clothing when working with the patient; maximum physical separation from other dogs in the same room; disinfection of all in-contact items such as food and water bowls, medical equipment, and bedding; the use of disinfectant foot baths or foot mats; and rigorous hand washing between patients. If staffing levels allow, personnel caring for influenza suspects should avoid contact with other hospitalized patients. When influenza outbreaks occur in groups of dogs, it is important to separate exposed or infected dogs from unexposed dogs. Because the infection spreads rapidly and virus shedding can precede the onset of clinical signs, all dogs present in a facility should be considered infected at the time of diagnosis. These animals should subsequently have no direct or indirect contact with unexposed dogs for 14 days. In addition to physical separation of exposed or infected dogs from unexposed susceptible dogs, it is important to avoid transmission by fomites such as clothing and equipment used by animal care personnel. If possible, exposed or infected dogs and unexposed susceptible dogs should be maintained in areas with separate air supplies and managed by separate teams of staff. However, these measures may not be possible in all facilities. Canine influenza virus is inactivated by many detergents and disinfectants. Hand washing with soap between patients reduces the spread of infection, and surfaces should be decontaminated by cleaning followed by disinfection. Cleaning is necessary to remove organic debris that may inhibit or inactivate disinfectants. Bleach, alcohol, quaternary ammonium compounds, and oxidizing agents are all effective for the inactivation of canine influenza virus.

Prevention Although a number of manufacturers are in the process of developing vaccines, at this time there are no licensed canine influenza vaccines on the market. Therefore the two main principles used in controlling canine influenza infection and disease are the reduction in the spread of virus between dogs and the prevention of secondary complications. Under optimal circumstances dogs should be isolated for up to 4 weeks before introduction into a ­disease-free population. During this isolation period no clinical signs should be detected, and no new

animals should be introduced into the isolation facility. Since these ­criteria may be too stringent for most animal facilities such as humane shelters and boarding kennels, 2 weeks of full isolation may constitute an acceptable compromise. Other management procedures such as segregating dogs in separate rooms can be valuable since segregation may allow for containment of disease outbreaks. As outlined previously, sharing of feeding, grooming, and cleaning equipment also increases the risk of disease spread.

Public Health Considerations As discussed in the introduction, influenza A viruses occasionally are transmitted directly from one host species to another. Yet in many instances these transmission events are self-limiting, and the introduced viruses are only rarely maintained in the new host species. Moreover, a number of influenza virus lineages are rarely detected in animals other than their typical host. For example, although the susceptibility of human volunteers to infection with H3 equine-lineage viruses has been demonstrated, there is no evidence that horse-to-human or human-to-horse transmission routinely occurs under natural conditions. Similarly, there is no evidence at this time that canine-tohuman transmission of influenza takes place. However, given the plasticity of the influenza virus genome, it is possible that at some time in the future the canine viruses may acquire the capability to infect another host species. This emphasizes the central role of the veterinarian in the control of canine influenza because only by continuing to sample animals with influenza-like illness and submitting these samples for virus isolation, antigenic, and genetic analyses will veterinarians be able to assess the extent of genetic evolution and to gauge the risks posed to other species by the canine H3N8 viruses.

References and Suggested Reading Crawford PC et al: Transmission of equine influenza virus to dogs, Science 310:482, 2005. Newton R et al: Canine influenza virus: cross-species transmission from horses, Vet Rec 161:142, 2007. Smith KC et al: Canine influenza virus, Vet Rec 157:599, 2005. Webster RG et al: Evolution and ecology of influenza A viruses, Microbiol Rev 56:152, 1992. Yoon K-J et al: Influenza virus infection in racing greyhounds, Emerg Infect Dis 11:1974, 2005. http://diaglab.vet.cornell.edu/issues/civ-stat.asp: Test summary for canine influenza virus in dogs not affiliated with greyhound racetracks.

C hapter 

285

Feline Infectious Peritonitis: Therapy and Prevention Diane D. Addie, Etchebar, France Takuo Ishida, Tokyo, Japan

F

eline infectious peritonitis (FIP) has been considered an incurable disease, and a diagnosis of FIP usually resulted in euthanasia. Recent advances in the understanding of FIP pathogenesis and novel diagnostic tests now enable earlier and more accurate diagnosis of FIP. With the recent introduction of recombinant feline interferon ω (rFeIFN-ω), there is hope for an effective treatment regimen in some cases. The first step in FIP treatment is establishing an accurate diagnosis. Despite many manufacturers’ claims that their tests are FIP tests, currently there is no specific FIP test. Existing tests actually detect feline coronavirus (FCoV) antibodies or viral RNA. Only histopathology can diagnose FIP unequivocally. This is because the majority of cats that become infected with feline coronavirus (FCoV) do not develop FIP (Fig. 285-1); therefore no healthy FCoV-infected cat should ever be said to have FIP. The problem for clinicians is distinguishing look-alike conditions from FIP in the FCoV-infected cat. Details of how to do this and further information can be found on catvirus. com or other literature sources.

Pathogenesis Cats become infected with FCoV orally, usually indirectly, by contact with FCoV-contaminated cat litter. FCoV is highly infectious, and in a multicat household over 90% of cats will seroconvert. Virus is shed in the feces from 2 days after infection, and cats seroconvert 18 to 21 days after infection. Initial infection may be clinically inapparent or accompanied by transient upper respiratory tract signs or diarrhea, which may be mild but can occasionally be extremely severe. Most cats clear the virus after 2 to 3 months of fecal shedding, although some cats are persistently infected. The mechanism for viral clearance is not wholly understood. Chronic carrier cats are usually healthy, although one of the authors (DA) has observed some cats develop chronic large intestinal diarrhea in older age. FCoV antibody titers in infected cats that do not develop FIP tend to decrease to zero over time (Addie and Jarrett, 2001). Increasing FCoV antibody titer in a healthy cat usually is followed by a decrease to zero over several months (Addie and Jarrett, 2001). However, in the experience of one of the authors (TI), if accompanied by polyclonal gammopathy and rising α1-acid glycoprotein (AGP) levels, rising antibody titers occasionally may be associated with FIP.

FIP is a misnomer since many cats do not present with peritonitis. The histopathologic lesion of FIP is a phlebitis or perivascular pyogranuloma. Recent developments in understanding the pathogenesis of FIP are useful in understanding how clinical signs develop and for devising new strategies for therapy. Using immunohistochemistry FCoV has been found within monocytes adhering to blood vessel walls and extravasating to adjacent tissues (Kipar et al., 2005). This is a key event in the development of FIP since FCoV-infected macrophages release a number of cytokines that drive the clinical disease. Interleukin6 (IL-6) stimulates B lymphocytes to differentiate into plasma cells, and high IL-6 levels found in cats with FIP are the likely cause of hypergammaglobulinemia. In early infection IL-6 stimulates hepatocytes to release acutephase proteins, including AGP and high AGP levels can be used to aid in the diagnosis of FIP. A rise in AGP levels was found not only in cats that develop FIP but also transiently in cats in contact with a sick FIP cat (Giordano et al., 2004), leading to speculation that the early AGP response could, in fact, be protective against FIP development (Addie, 2004). Why one cat develops FIP while other infected in­contact cats remain healthy is unknown. Some laboratory strains are exceptionally virulent, causing FIP in almost every cat infected with them; these have been called FIPVs. There are also biotypes with far less virulence, commonly called feline enteric coronaviruses (FECVs). These laboratory strains have varying ability to replicate in monocytes, and it has been assumed that the occurrence of FIP was related solely to the virulence of the strain of virus infecting the cat. However, a recent study has shown that monocytes of different cats support FCoV replication to varying extents (Dewerchin, Cornelissen, and Nauwynck, 2005) and that some cat’s monocytes do not support viral replication at all, which could be an explanation for the occurrence of FCoVresistant cats previously reported by Addie and Jarrett (2001). The “internal mutation theory” (i.e., that FECVs must mutate to FIPVs for FIP to arise) has been questioned after sequence analysis of the entire genome of viruses found both in the gut and systemically in a cat that died of FIP were found to be identical (Dye and Siddell, 2007). The recent advent of quantitative (or real-time) polymerase chain reaction will enable the role of viral load in FIP development to be investigated more fully. 1295

1296

Section  XIII  Infectious Diseases

Transient FCoV infection (65% of FCoV infections)

Persistent infection (13% of infected cats) FCoV FIP (5%-10% of infections)

Resistant to FCoV infection (~3%)

Fig. 285-1  Potential outcomes of feline coronavirus infection. (The percentages are approximate and do not add up to 100% because not all of the cats in the study had sufficient samples taken for their status to be defined [Addie and Jarrett, 2001]).

Therapy Current Therapies Clinical FIP is caused by the cat’s inflammatory and immune-mediated response to FCoV. Therapy is aimed at suppressing that inflammatory and immune-­mediated response, usually with corticosteroids. One problem with corticosteroid therapy is that it suppresses the immune response nonselectively, suppressing both cell-mediated and humoral immune responses. It is likely that one would wish to support cell-mediated responses while suppressing humoral responses, at least in effusive FIP. It is possible that in noneffusive FIP both cell-mediated and humoral responses should be suppressed. Until recently FIP was almost 100% fatal. However, two publications have reported cure or remission in some cats.

Administration of a thromboxane synthetase inhibitor with prednisolone reportedly cured one cat and gave remission for 8 months in a second effusive FIP (Watari et al., 1998). However, one of the authors (TI) has been unable to reproduce this result. Use of rFeIFN-ω (Virbagen-ω, Virbac) and prednisolone resulted in recovery in 4 of 12 cats and remission of 4 and 5 months in two others (Ishida et al., 2004). However, a second study evaluating rFeIFN-ω therapy was unable to show an effect on survival time or quality of life in cats with FIP (Ritz, Egberink and Hartman, 2007). IFN-ω is a monomeric glycoprotein distantly related in structure to IFN-α and IFN-β but unrelated to IFN-γ. It has antiviral properties, stimulates natural killer cell activity, and enhances expression of major histocompatibility complex class I (but not class II) antigens. Although effusive and noneffusive FIP are not distinct diseases but rather gradations of the same process. The use of interferons for the treatment of cats infected with FIP is controversial, though the authors believe such therapy is warranted considering the relative lack of therapeutic options. Both negative treatment studies (Ritz, Egberink, and Hartmann, 2007) and positive treatment studies (Ishida et al., 2004) have been published. Our treatment approach to the cat with an effusive or noneffusive form of FIP infection is outlined in Box 285-1. Only over time and with additional studies will the effectiveness of rFeIFN-ω or other therapies in the treatment of FIP become evident.

Possible Future Therapies A number of other drugs also have theoretic application in the treatment of cats with FIP and are offered in Table 285-1. Most have never been used to treat FIP or have been used in only a few cats; thus the reader should exercise appropriate caution when choosing patients to receive these unproven drugs.

Box  285-1 Treatment Protocols Used for Effusive and Noneffusive Feline Infectious Peritonitis EFFUSIVE Glucocorticoids Dexamethasone 1 mg/kg intrathoracic, intraperitoneal or intravenous once followed by: • Prednisolone sliding dose; 4 mg/kg q24h for 10-14 days, reducing to 2 mg/kg q24h for 10-14 days, then 1mg/kg q24h for 10-14 days, then 0.5 mg/kg q24h for 10-14 days, then 0.25 mg/kg q24h for 10-14 days, then 0.25 mg/kg q48h and so on, ceasing after complete remission of clinical signs; if, at any point, the cat’s condition regresses, go back to the previous dose Feline interferon-w 1 million units(MU)/kg subcutaneously q48h, reducing to once weekly if remission occurs Broad-spectrum antibiotics

Noneffusive Glucocorticoids Prednisolone sliding dose as for effusive feline infectious peritonitis (FIP); with FIP-related uveitis topical corticosteroids should be used. Feline interferon-w 50,000 units per cat PO q24h until acid glycoproteins, serum amyloid A, globulins, hematocrit, lymphocyte count, and clinical signs return to normal. Diluting feline interferon-w Feline interferon (IFN)- ω (Virbagen Omega, Virbac) comes in vials of 10 MU. It is reconstituted with 1 ml of diluent. Ten aliquots of 0.1 ml (1 MU per syringe) are prepared in insulin syringes. Nine syringes out of 10 are kept in the freezer (can be stored up to 6 months). The tenth syringe is diluted with 19.9 ml of sterile 0.9% saline solution to obtain 20 ml of solution containing a total of 1 MU (50,000 U/ml) of feline IFN-ω. This syringe is stored in the refrigerator at +4 ° C, where it will last up to 3 weeks (do not freeze diluted IFN-ω because it is unstable). Dosage: 1 ml of this diluted solution (containing 0.05 MU) orally daily, using the syringe without the needle.

Chapter  285  Feline Infectious Peritonitis: Therapy and Prevention



1297

Table 285-1 Potential Future Drugs for the Treatment of Feline Infectious Peritonitis* Potential Treatment

Suggested Mode of Action

Suggested Dosage

Comments

Ozagrel hydrochloride

Thromboxane synthetase inhibitors

5-10 mg/kg twice a day

Infliximab (Remicade, Centocor)

Monoclonal antibody against tumor necrosis factor (TNF)-α

Unknown

Etanercept (Enbrel, Immunex Corp.)

Soluble p75 TNF-α receptor coupled to Fc portion of immunoglobulin G

Unknown

Dehydroepiandrosterone (DHEA)

Down-regulates endothelial adhesion molecules and reduces neutrophil extravasation Synthetic derivative of DHEA

Cured one cat and gave ­ remission for 8 months in a second effusive feline ­infectious peritonitis (FIP); no cures in a second study (Ishida, unpublished) Use in effusive and noneffusive FIP; increases risk of bacterial infections Use in effusive and noneffusive FIP; increases risk of bacterial infections Use in effusive but not in noneffusive FIP

16α-Bromo-epiandrosterone (epiBr) Cimetidine Thalidomide Salvianolic acid B Tropisetron Coronavirus 3C–like protease inhibitors

40 mg/cat/day

Stimulates cell-mediated immunity and reverses lymphopenia Antiinflammatory and pushes immune response from Th2 to Th1 Matrix metalloproteinase 9 inhibitor 5-hydroxytryptamine (3) receptor antagonist Anticoronavirus drug

50 mg once a day 50-100 mg once a day in the evening 10 mg/kg once a day

Use in effusive but not innoneffusive FIP Safe; may be more useful in effusive than noneffusive FIP Safe but difficult to source Likely to be more useful in effusive than noneffusive FIP

300 mcg/kg once a day Intravenous administration likely

Not yet available

*note: Listed in Table 285-1 are potential theoretic treatments for cats with FIP that are lacking published clinical or research studies. The reader should exercise appropriate caution in use of these unproven drugs.

Prevention of Feline Infectious Peritonitis and Feline Coronavirus Infection There is no single, easy method to prevent FIP; a combination of the techniques discussed in the following paragraphs is most effective. Obviously, if cats do not become infected with FCoV, FIP will not develop.

Prevention of Feline Infectious Peritonitis by Vaccination The one commercially available FIP vaccine, a temperature-sensitive mutant (Primucell, Pfizer) that only replicates in the cooler nasal mucosa of cats, has been beset by controversy (also see Chapter 280). Basically there are two questions: is it effective, and does it cause antibodydependent enhancement of disease? In an independent study in Switzerland, cats entering a rescue cattery were vaccinated with Primucell. There was no difference in mortality rates from FIP between vaccinated and unvaccinated cats in the first 150 days after vaccination (Fehr et al., 1995, 1997). However, after 150 days there was a marked reduction in the number of cats succumbing to FIP in the vaccinated but not the control group. When the investigators returned to stored blood samples from the cats that developed FIP, they found

that these cats were already viremic at the time of vaccination (Fehr et al., 1997) (i.e., they were incubating FIP at the time of vaccination). Only FCoV-naive cats can be ­prevented from developing FIP by vaccination. From this study it is possible to suggest certain vaccine guidelines: • All cats going into rescue and boarding catteries should be vaccinated against FIP. • Cat breeders should maintain their kittens FCoV-free until FIP vaccination is possible (current recommendation is that vaccination commences at 16 weeks of age). Another point sometimes made in relation to the efficacy of Primucell vaccine is that it is derived from a type II FCoV, the strain DF2. There are two types of FCoV: type I, which is wholly feline; and type II, which is a recombinant virus with much of the viral spike protein being derived from canine coronavirus. The majority of field strains of FCoV are type I. In the study mentioned previously, it is likely that most of the FCoVs the cats naturally encountered in the rescue shelter were type I since a recent study showed that type I is the most prevalent type in Switzerland (Kummrow et al., 2005). Thus, although unproven, the vaccine is likely to be equally effective against types I and II FCoV.

1298

Section  XIII  Infectious Diseases

Antibody-dependent enhanced (ADE) FIP is a phenomenon in which vaccination contributes to disease pathogenesis. ADE FIP is the reason why most experimental FIP vaccines have failed (i.e., more vaccinated cats than unvaccinated cats developed FIP, and they did so more quickly and with worse clinical and pathologic features than unvaccinated cats). In two laboratory experiments in which Primucell appeared to cause ADE, a highly virulent laboratory strain of FCoV was used in the challenge (McArdle et al., 1995; Scott, Olsen, and Corapi, 1995). In contrast, in two field trials with Primucell the vaccine was protective (Fehr et al., 1995, 1997; Postorino-Reeves, 1995). One recommendation of the Second International Feline Coronavirus and Feline Infectious Peritonitis Symposium workshop was that the 79–1146 strain of FCoV not be used in vaccine challenge experiments since it is too virulent to give an accurate representation of how the vaccine would perform in field conditions (Addie et al., 2004).

Prevention of Feline Coronavirus Infection and Feline Infectious Peritonitis by Hygiene and Quarantine FIP vaccination is not 100% protective; thus it is preferable that cats never be exposed to FCoV infection. This is especially true for cat breeders and their kittens since kittens cannot be vaccinated before 16 weeks of age but they are susceptible to infection after 5 to 6 weeks of age. Indeed, in large catteries virus load may even overcome maternally derived antibody to cause infection in kittens as young as 2 weeks (Addie et al., 2004). FCoV is shed mainly in feces; therefore avoiding FCoV infection centers around litter tray hygiene and limiting contact of FCoV-naive cats with FCoV-contaminated cat litter or fomites. FCoV is killed by many disinfectants, including household bleach. Regular disinfection of litter trays helps to minimize environmental viral load. Provision of adequate numbers of litter trays in multicat households helps ensure that cats do not have to use a soiled tray, and self-cleaning litter trays or nontracking cat litter should be used wherever possible. Regular vacuum cleaning reduces environmental contamination by microscopic particles of infected cat litter. FCoV infection is maintained in a household or cattery by continual cycles of infection and reinfection (Foley et al., 1997, Addie et al., 2003). Commonly available reverse transcriptase polymerase chain reaction tests can detect FCoV in feces, so that it is possible to establish which cats are shedding FCoV and separate them from cats that are not shedding FCoV. Virus shedding usually continues for 2 to 3 months, although it can be longer. Cats that shed FCoV for 9 months or more are likely to be lifelong carriers of the virus (although one cat stopped shedding virus after 5 years). By repeat testing and separation of shedding from nonshedding cats, it is possible to eliminate FCoV from a multicat pet or breeding household. Quarantine and testing of newarrival cats prevents FCoV from being (re)introduced into such a household. Kittens are protected from FCoV infection by maternally derived antibodies until they are between 5 and

6 weeks of age. Thus it is possible to prevent FCoV infection of young kittens by isolating them with their queens from birth onward and removing them to a clean environment when they are 5 to 6 weeks old. For this technique to work, the breeder requires a thorough understanding of barrier nursing techniques. Transplacental transmission of FCoV does not appear to occur. Many cats with FIP have a history of having recently been stressed (e.g., by a neutering operation). Cats at risk for FIP are easy to identify: they are purebred or have a history of having come from a multicat environment such as a rescue shelter or pet shop. Fifty percent of FIP occurs in cats under 2 years old. It is possible that the development of FIP in these cats could be averted by determining whether or not they are infected (e.g., by testing their feces for FCoV) and delaying elective surgery until the cat has cleared the virus. Cats are at greatest risk of developing FIP soonest after FCoV infection (Addie et al., 1995), and the risk diminishes with time. When there is no choice but to go ahead with surgery, stress can be minimized as much as possible (e.g., by not keeping the cat in a waiting room with dogs). For the reasons outlined previously, it would be prudent to advise clients to avoid stresses such as visits to the boarding cattery until FCoV-infected cats have cleared the virus. In summary, FIP therapy is still in early stages and likely can only be advanced after a definitive diagnostic test is developed. Therefore all efforts should be directed to preventing FIP by careful cat management (good hygiene, stress reduction, quarantine) and by vaccination.

References and Suggested Reading Addie DD: Feline coronavirus: that enigmatic little critter, Vet J 167:15, 2004. Addie DD: Feline infectious peritonitis. In de Mari K, ed: Veterinary interferon handbook, ed 2, Carros, France, 2008, Virbac Animal Health, p 132. Addie DD, Jarrett O: A study of naturally occurring feline coronavirus infection in kittens, Vet Rec 130:133, 1992. Addie DD, Jarrett JO: Use of a reverse-transcriptase polymerase chain reaction for monitoring feline coronavirus shedding by healthy cats, Vet Rec 148:649, 2001. Addie DD, Paltrinieri S, Pedersen NC: Recommendations from workshops of the second international feline coronavirus/ feline infectious peritonitis symposium, J Feline Medicine Surgery 6:125, 2004. Addie DD et al: The risk of feline infectious peritonitis in cats naturally infected with feline coronavirus, Am J Vet Res 56(4):429, 1995a. Addie DD et al: The risk of typical and antibody-enhanced feline infectious peritonitis among cats from feline coronavirus endemic households, Feline Pract 23(3):24, 1995b. Addie DD et al: Persistence and transmission of natural type I feline coronavirus infection, J Gen Virol 84 (Pt 10):2735, 2003. Dewerchin HL, Cornelissen E, Nauwynck HJ: Replication of feline coronaviruses in peripheral blood monocytes, Arch Virol 150:2483, 2005. Dye C, Siddell SG: Genomic RNA sequence of feline coronavirus strain FCoV F1Je, J Feline Med Surg 9(3):202, 2007. Fehr D et al: Evaluation of the safety and efficacy of a modified live FIPV vaccine under field conditions, Feline Pract 23:83, 1995.

Chapter  286  Control of Viral Diseases in Catteries

Fehr D et al: Placebo-controlled evaluation of a modified life virus vaccine against feline infectious peritonitis: safety and efficacy under field conditions, Vaccine 15(10):1101, 1997. Foley JE et al: Patterns of feline coronavirus infection and fecal shedding from cats in multiple-cat environments, J Am Vet Med Assoc 210(9):1307, 1997. Giordano A et al: Changes in some acute phase protein and immunoglobulin concentrations in cats affected by feline infectious peritonitis (FIP) or exposed to feline coronavirus infection, Vet J 167:38, 2004. Ishida T et al: Use of recombinant feline interferon and glucocorticoid in the treatment of feline infectious peritonitis, J Feline Med Surg 6(2):107, 2004. Kipar A et al: Morphologic features and development of granulomatous vasculitis in feline infectious peritonitis, Vet Pathol 42:321, 2005. Kummrow M et al: Feline coronavirus serotypes 1 and 2: seroprevalence and association with disease in Switzerland, Clin Diagn Lab Immunol 12:1209, 2005. McArdle F et al: Independent evaluation of a modified-live FIPV vaccine under experimental conditions (University of Liverpool experience), Feline Pract 23:67, 1995.

C hapter  

1299

Postorino-Reeves N: Vaccination against naturally occurring FIP in a single large cat shelter, Feline Pract 23:81, 1995. Ritz S, Egberink H, Hartmann K: Effect of feline interferon-omega on the survival time and quality of life of cats with feline infectious peritonitis. J Vet Intern Med 21:1193, 2007. Scott FW, Olsen CW, Corapi WV: Independent evaluation of a modified live FIPV vaccine under experimental conditions (Cornell experience), Feline Pract 23(3):74, 1995. Watari T et al: Effects of thromboxane synthetase inhibitor on feline infectious peritonitis in cats, J Vet Med Sci 60:657, 1998.

Useful Feline Coronavirus/Feline Infectious Peritonitis Websites www.catvirus.com: FCoV/FIP website with the latest information for veterinary surgeons and information for cat guardians and breeders. www.felinecoronavirus.com: website for FCoV/FIP symposia news. www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed: National Institutes of Health website with search facility for finding the latest scientific and veterinary publications on FCoV and FIP.

286

Control of Viral Diseases in Catteries Diane D. Addie, Etchebar, France

T

he control of viral disease in catteries will depend largely on the type of cattery. Catteries mainly fall into six distinct types with different feline populations:

1. Boarding/Quarantine: Transient population, but mainly vaccinated. Indoor for duration of cattery stay, but possibly free-ranging before then. 2. Rescue: Transient population of unknown vaccine status. Indoor for duration of cattery stay, but a mix of free-ranging and indoor housing prior to relinquishment. 3. Breeding: Longer term population, closed, but with possible contact with other cats for mating, or at shows. Vaccination and infectious disease screening variable. Usually indoor housing. 4. Multicat pet household: Longer term population, free-ranging or indoor housing. Vaccination and infectious disease screening variable.

5. Veterinary premises: Transient population of known and unknown infectious disease status. 6. Specific pathogen free (SPF): Closed, indoor population with strictly known vaccination and infectious disease status. Clearly, the problems encountered within each of the different types of cattery are extremely diverse. In this chapter I will approach the control of the main feline viral diseases, referring only to cattery type when it affects the control of that particular virus. The infections considered in this chapter are listed in Table 286-1. Information on more unusual viral infections, such as Borna virus and Aujeszky’s (pseudorabies), are considered in other textbooks (Greene, 2006). Full clinical details, treatment, and diagnosis of viral diseases are omitted in this chapter, except where they affect disease control (for more therapy details, see Section XIII in this volume). The most

1300

Section  XIII  Infectious Diseases

Table  286-1 Viral Transmission and Shedding Infection

Survival Outside Host

FCV

Days to weeks

Continuous, half-life 75 days

FHV

12-18 hours

FeLV

Quarantine Time Before Testing

Mode of Transmission

Prevention of Infection

7 days

Direct contact, sneezed droplets

Intermittent, lasts 7-14 days

3 weeks

Direct contact, sneezed droplets

Minutes

Continuous

12 weeks

FIV

Minutes

Continuous*

12 weeks

FCoV/FIP

Up to 7 weeks

Usually continuous

3 weeks (antibody, 1 wk virus)

Parvovirus

Up to a year

Usually only 24-48 hours, but can be up to 6 weeks

None

Direct contact essential, transplacental Direct contact essential—mainly biting; transplacental rare Indirect, through cat litter/shared litter trays, poop scoops; not transplacental Indirect, transplacental

Test all cats before mixing them; excellent hygiene; sneeze barriers Vaccination prevents clinical signs, but not infection; testing reliable if positive result, but since latent infection, negative result not definite Test all cats before mixing them; vaccination Test all cats before mixing them

Not infectious to other cats Continuous

None

Feline pox virus Rabies

Minutes

Virus Shedding

None if adequate antibodies: >0.5 units or 6 months

Contact with small rodents Biting

Test all cats before mixing them; excellent hygiene

Vaccination; excellent hygiene and disinfection; don’t have too many unvaccinated cats/kittens on premises Can’t stop cats hunting! Vaccination is effective

FCV, Feline calicivirus; FCoV, feline coronavirus; FeLV, feline leukemia virus; FHV, feline herpesvirus; FIV, feline immunodeficiency virus; FIP, feline infectious peritonitis. *Virus load is very low during the long asymptomatic phase.

e­ ssential part of infectious disease control in all types of cattery, and for all infectious diseases, is good hygiene, so we will begin with that.

Control Of Viral Transmission By Hygiene The essence of “barrier nursing” is preventing transfer of infection within the cattery. Clean cats/food bowls/litter trays/pens should be dealt with before dirty ones. The cats’ food should be distributed before dealing with litter trays or cleaning kennels; ideally there would be different people dealing with the food and the cleaning. Clean litter trays should be put out in the runs first, and then the dirty trays should be picked up; a clean tray should never be touched after a dirty one, and the same poop scoop or litter rake should never be used from one pen to another! The first rule is to deal first with the leastinfected area of the surgery or cattery (for example, any kittens or surgery cases), and gradually move up to the most-infected area (locations where there are animals sick with infectious disease or known healthy carriers of infection). It is usefulto establish a routine order of tending to the animals in a cattery so that the least-infected

area is always dealt with first. This applies to cleaning of litter trays, feeding, grooming, or even when the cats are petted. Indirect transmission of viruses can occur on hands, shoes, or clothes when moving about the cattery. Therefore hands should be washed or disinfected before every contact with a cat or kennel. Ideally there should be disinfectant foot baths between each major area of a cattery. Kittens should have food bowls, litter trays, and litter scoops that are used only for them, and these should be cleaned daily and disinfected/steam cleaned once or twice a week. The beds, dishes, litter trays, and scoops of cats in different areas of the cattery should be color coded so that it is immediately obvious if something is in the wrong place. Thus if a kitten’s litter tray had been inadvertently put into the pen of an adult cat, it could be spotted instantly, removed, and disinfected before being returned to the kittens’ area. Cattery design is crucial. Sneeze barriers are essential for the control of airborne viruses in all cattery categories except for the pet household. It is vital that air conditioning pushes the air past the cat straight to the outdoors (i.e., positive ­pressure rather than negative pressure) or to a virus filter system and not past other cats.

Quarantine is useful to establish whether new cats are incubating disease. For example, feline herpesvirus (FHV) shedding recrudesces following stress, and the biggest stress a cat can face is being rehomed or going to a boarding cattery; thus virus is shed again, with or without accompanying upper respiratory tract signs. The United Kingdom quarantines cats from countries with endemic rabies for up to 6 months to allow them time to display clinical signs of rabies if they were infected. The time required for quarantine depends on which pathogen is the concern (see Table 286-1).

Feline Calicivirus Feline calicivirus (FCV) is a ribonucleic acid (RNA) virus. It exists in cats as a quasispecies, continually mutating to evade the neutralizing antibodies of its host (Radford et al., 1998). Vaccination ameliorates clinical signs but doesn’t prevent virus shedding and may even promote carrier status. Indeed, 40% of so-called vaccine breakdowns are caused by the vaccinal strain. If a live vaccine is aerosolized or inadvertently spilled onto the cat and the cat licks it off, it can infect the cat; thus catteries that are free of FCV ­preferably should use killed, or antigen-only, vaccines. Natural selection has driven field strains of FCV away from older vaccine strains. In cattery situations vaccines containing newer FCV strains should be used to give as broad a protection as possible. FCV strains causing virulent systemic disease (VSD) (Pesavento et al., 2004; Coyne et al., 2006) tend to arise de novo in the cattery situation; therefore there is no benefit in vaccines containing a FCV VSD strain. For situations in which rapid onset of protection is needed, intranasal vaccines should be considered (Radford et al., 2007). Vaccination alone will not prevent FCV spread in a cattery. SPF and breeding catteries can avoid its introduction completely by testing new cats prior to introduction, provided the test is sensitive enough (virus isolation of an oropharyngeal swab). Reverse transcriptase–polymerase chain reaction [RT-PCR] has to be used with caution because of the high variability of the FCV genome; some tests will give false negative results. Fortunately FCV is shed continuously (as opposed to intermittently). FCV is shed by 10% of pet cats, 25% of cats at shows, 40% of colony cats, and almost 100% of cats with chronic lymphocytic plasmacytic gingivostomatitis. The halflife of FCV shedding is 75 days; thus there should be 2.5 months between tests of cats to detect when they have stopped shedding FCV. Cat breeders preferably should use only FCV-negative queens. If this is not possible, maternally derived antibody (MDA) lasts up to 2 to 3 weeks; thus kittens can be weaned early and kept in isolation from infected individuals. At time of writing, no antiviral drug is effective against FCV.

Feline Herpesvirus FHV-1 is a deoxyribonucleic acid (DNA) virus, and there is essentially only one serotype (reports of a FHV-2 were never fully scientifically confirmed). Viral persistence in the host cat is completely different from the other flu

Chapter  286  Control of Viral Diseases in Catteries

1301

virus, FCV, in that FHV becomes latent within the trigeminal ganglion of the host. The trigeminal ganglion is an immune-privileged site, and the DNA of the FHV exists in the ganglion without expressing viral proteins. However, if the cat is stressed (e.g., because of rehoming or pregnancy), the virus can re-emerge, travel down the trigeminal nerve, and be shed in the oropharynx and/or the eye. Recrudescence of FHV shedding occurs 7 to 10 days after stress and lasts for 1 to 2 weeks. Vaccination prevents the worst of clinical signs, but does not prevent infection of the cat or the development of latency. It is estimated that 90% of cats have been exposed to FHV and 80% of exposed cats become latently infected for life. Testing for infection is of limited value because negative results may simply mean that the virus was latent at the time of testing. As with FCV, prevention of FHV depends on factors such as good hygiene. However, the amino acid l-lysine competes with arginine in the formation of the herpesvirus particle, and a dosage of 250 to 500 mg/cat/day may reduce FHV shedding. Breeders attempting to reduce FHV infection of the neonate may stress the queen 3 to 4 weeks before kittening by moving her to a room or chalet on her own so that FHV shedding will have passed by the time the kittens are born. MDA is only protective for up to 2 to 3 weeks; thus the kittens should be weaned early and then kept in total isolation from the adult cats in the household. Aside from topical preparations for ocular FHV, use of human antiherpesvirus drugs in cats is limited by their poor efficacy against FHV and by their toxicity in the cat (Maggs, 2001).

Feline Leukemia Virus Feline leukemia virus (FeLV) is an RNA retrovirus. For an RNA virus it is remarkably conserved. The virus has avoided the need to mutate to evade the cat’s immune response by switching off the cat’s immune response, which is why it causes immunodeficiency. FeLV is a fragile virus, requiring direct contact for transmission. Transplacental transmission occurs. Infection to viremia takes 3 to 6 weeks, which is why it is important to retest a negative cat suspected of FeLV exposure after 6 to 12 weeks. Following oronasal exposure, FeLV infects local lymph nodes and travels to bone marrow and other lymphoid tissues. It then moves to mucosa, where it is shed mainly in the saliva (although possibly in the tears, urine, feces, and milk as well). The cat has the opportunity to recover at any of these stages of infection, so it is important to retest a healthy cat with a positive FeLV test after an interval of 12 weeks. After the age of 4 months cats are increasingly able to mount an effective immune response to FeLV. However, this age-related resistance to FeLV can be overwhelmed by high viral doses such as are found in infected multicat households in which approximately 40% of cats can be viremic. Cytotoxic T cells appear early in FeLV infection (in a week). Immunity to natural FeLV exposure can be measured by detecting virus-neutralizing antibodies (VNAs), which appear from 6 weeks after infection.

1302

Section  XIII  Infectious Diseases

Cats with active FeLV infection have a VNA titer of 0. The immune response to vaccines is not easy to measure commercially. No FeLV vaccine is 100% effective. Vaccination has a place in free-roaming pet cats but should not be necessary for veterinary surgeries or boarding or rescue catteries (since cats from different backgrounds should not be allowed to mix and FeLV is unlikely to be transmitted indirectly). Neither should breeding or SPF catteries require vaccination, since these cats are usually kept indoors and should have been tested and found to be FeLV negative before being introduced into these catteries. It is important to use in-house diagnostic tests for FeLV wisely (Table 286-2). Point of care FeLV tests for FeLV p27 antigen should be considered as screening tests; accordingly, a positive result should be confirmed by a more specific test, such as immunofluorescence (IF), virus isolation (VI), or polymerase chain reaction (PCR), which will usually be carried out by a specialist or reference laboratory. The reason for confirmation is that in situations in which the prevalence of FeLV infection is very low, as is the case in many populations of healthy cats, the positive predictive value of an in-house test is relatively low (i.e., the occurrence of false positive results is relatively high). Cats that are persistently viremic will test positive with all of these diagnostic tests. The advantage of immunofluorescence and virus isolation tests is that they definitively detect viremic, virus-excreting cats and can be considered the gold standard for FeLV diagnosis. PCR is very sensitive and detects proviral DNA in leukocytes. However, many, if not all, cats that recover from FeLV infection and lead perfectly healthy lives without excreting virus will also be positive on PCR testing. Quantitative, real time PCR avoids some of this problem in that high virus load is associated with viremia, but it cannot discriminate completely between viremic and nonviremic cats.

Feline Immunodeficiency Virus Feline immunodeficiency virus (FIV) is a fragile RNA retrovirus, easily killed by disinfectants. FIV usually is not transmitted indirectly, except by reusing syringes or operating kits or using dental descalers from cat to cat without sufficient hygiene. It is transmitted mainly by biting and occasionally by sharing food bowls or mutual grooming. It is rarely transmitted transplacentally or in the milk, but it is possible that an FIV-positive queen could infect her kittens when she bites through the umbilical cord or when she grooms them. Most FIV tests detect antibody, not virus (the major exception being PCR, which detects viral DNA as provirus in the cat’s genome). The period from infection to seroconversion takes up to 12 weeks; therefore antibody testing should be 12 weeks after suspected exposure. In-house FIV antibody tests can give false-positive results; thus they should be confirmed by gold standard tests (immunofluorescence, western blotting) (see Table 286-2). In addition, some FIV-infected cats don’t have detectable antibody; thus a viral detection test such as PCR of the buffy coat should be used. Transmission of FIV should not be an issue in most catteries, provided that cats from different backgrounds aren’t mixed. The main situation in which FIV is a problem is the multicat pet household (cats can be screened before introduction, but if they are free ranging, they may become infected at any time). At time of writing there is one commercially available FIV vaccine in the United States; it causes positive antibody tests. As in FeLV infection, FIV vaccination won’t be required in breeding, SPF, boarding catteries, or veterinary surgeries since there should be no opportunities for transmission in these environments.

Table  286-2 Use of In-House Feline Leukemia Virus and Feline Immunodeficiency Virus Tests in Different Cattery Types Type of Cattery

Whether Cats are Tested

Boarding/quarantine Rescue

Not usually tested Sometimes tested

Breeding

Always tested

Multicat pet household

Sometimes tested

Veterinary premises

Rarely screened unless symptomatic Always screened

Specific pathogen free

Action After Use of In-House Test Positive results must be confirmed since the cat may be euthanized. Negative results from testing a healthy animal are fine but from a sick animal should be confirmed. Positive results likely to be false positive if pedigree cat from FeLV- and FIV-negative background; therefore confirm using gold standard test.* Isolate cat and retest after 12 weeks. Confirm all positive results. If symptomatic, negative results should be confirmed using gold standard test.* Positive results likely to be false positive; therefore confirm using gold standard test.*

FeLV, Feline leukemia virus; FIV, feline immunodeficiency virus. nB: FeLV vaccination does not affect in-house test results. nB: FIV vaccination can cause positive antibody test results. FIV tests will detect maternally derived antibody until around 16 weeks of age in uninfected kittens of FIV-positive queens. *Gold standard tests for FeLV are virus isolation and immunofluorescence. Gold standard tests for FIV are western blotting and immunofluorescence.



Chapter  286  Control of Viral Diseases in Catteries

Feline Coronavirus/Feline Infectious Peritonitis

Box  286-1

Feline coronavirus (FCoV) is an extremely infectious virus; over 90% of cats that encounter it seroconvert. FCoV is an RNA virus that mutates frequently. In the literature there are references to feline enteric coronavirus (FECV) as an avirulent FCoV responsible for the large number of seropositive cats in the absence of feline infectious peritonitis (FIP). However, it is now widely recognized that all strains of FCoV have the potential to cause FIP. There are essentially two types of FCoV: type I is wholly feline; type II FCoVs arise by recombination with canine coronavirus (CCoV), and much of the spike of the type II FCoV is canine. About 90% of field isolates are type I; 10% are type II.

Protocol for Minimizing Feline Coronavirus Introduction or Spread in a Cattery*

Feline Infectious Peritonitis Prevention and Feline Coronavirus Control The key to prevention of FIP is to prevent FCoV infection. FCoV infection is perpetuated by a cycle of infection, virus shedding, development of immune response, loss of humoral immunity, and reinfection. In breeding catteries and ordinary pet households, control has been affected by excellent hygiene and by separating immunofluorescent antibody test (IFAT) seropositive and seronegative cats. Cats are tested every 3 to 6 months, and as their antibody titer falls they are put into a seronegative group, which is kept isolated from the seropositive group. Detection of virus is less useful, since cats can shed FCoV intermittently (see following paragraphs). The fewer cats in the cattery (or household), the better the chance of eliminating FCoV. Once a cattery is free of FCoV, all new cats should be antibody-tested negative before introduction. Cat breeders should antibody test their cats for FCoV annually and only mate positive cats with other positive cats and negative cats with negative cats. Kittens of ­positive-to-positive cat matings can be prevented from becoming infected by early weaning and isolation. FCoV is only shed transiently (a few days) in the saliva of a minority of cats. The main source of virus is the feces, and infection is by accidental ingestion of particulate feces (e.g., from grooming paws after using a litter tray or from airborne particles from a litter tray contaminating food). FCoV is a fragile virus, surviving only days outdoors, but it can survive indoors up to 7 weeks in dried feces in cat litter particles. See Chapter 285 and Box 286-1 for recommendations on minimizing exposure to FCoV. FCoV does not generally cross the placenta.

Vaccination Experimental FIP vaccines have been plagued with the problem of inducing antibody-dependent enhanced disease (i.e., in which vaccinated cats are more likely to die of FIP than unvaccinated cats), and only a single FIP vaccine, Primucell (Pfizer) is commercially available.Primucell is a temperature-sensitive mutant that is instilled intranasally and gives rise to local immunoglobulin A and cell-mediated immunity. Primucell prevents FIP in 50% to 75% of cats that would have otherwise developed it but is ineffective in cats

1303

A. Reduce the numbers of cats in any area. • Ordinary house owners should keep no more than 6 to 10 cats. • Cats should be kept in stable groups of up to three or four. • In rescue facilities cats should be kept singly. • In an FCoV eradication program cats should be kept in small groups according to their antibody or virus ­excretion status. • Antibody- or virus-negative cats together • Antibody- or virus-positive cats together B. Avoid introducing virus to uninfected cats: antibody or virus testing. • Incumbent cats should be tested before introducing new cats or breeding. • Only antibody- or virus-negative cats should be ­introduced into FCoV-free catteries. • It is safer to introduce antibody-positive cats than ­antibody-negative cats into FCoV-infected households, but there is still a risk of FIP in both the newcomer and the incumbent cats. C. Prevent kitten infection: early weaning and isolation. • Both cat breeders and rescuers of pregnant cats should follow the protocol outlined in Table 286-2. D. Reduce fecal contamination of the environment. • Have adequate numbers of litter trays—at least one tray per cat. • Litter trays should be declumped at least daily. • Choose a nontracking cat litter. • Remove all litter and disinfect litter tray at least once a week. • Place litter trays away from the food area. • Vacuum around litter trays regularly. • Clip fur off hindquarters of long-haired cats. E. Vaccinate with Primucell. • If new cats must be introduced into a household with endemic infection, they should receive a full course of Primucell vaccine before introduction. • When economically possible, rescue catteries should ­vaccinate all new cats with Primucell. FCoV, Feline coronavirus. *Based on recommendations from working groups of the international feline enteric coronavirus and feline infectious peritonitis workshop. (From Pedersen NC, Addie D, Wolf A: Recommendations from working groups of the international feline enteric coronavirus and feline infectious peritonitis workshop, Feline Pract 23:108, 1995.)

­ reviously exposed to FCoV. Thus in catteries wherein FCoV p is endemic (most cat breeders’ catteries), Primucell must be used in kittens that have already undergone a special management procedure known as early weaning and isolation so they are FCoV free when vaccinated. In addition, we know that Primucell vaccination does not prevent a cat from shedding FCoV (Addie, unpublished observations).

Feline Coronavirus Prevention in Kittens Kittens are protected from FCoV infection by MDA, which wanes at around 5 to 6 weeks. This discovery has enabled the breeding of uninfected kittens even in households

1304

Section  XIII  Infectious Diseases

in which FCoV is endemic and the queen is infected. Essentially the queen is isolated before giving birth in a single room or pen that has been well cleaned. The queen and litter are maintained in isolation with barrier nursing until the kittens are 5 to 6 weeks of age, when the queen is removed and the room thoroughly cleaned again. New clean litter trays are introduced. Detailed information about early weaning and isolation for owners is available on the Internet (www.catvirus.com), and a summary is given in Box 286-2.

Feline Coronavirus Tests For control of FCoV to work, use of a reliable antibody test is essential. Samples split and sent to five different laboratories in the United States gave five completely different results (Postorino-Reeves, personal communication). The IFAT is the gold standard, but there is a risk of false positive results if antinuclear antibodies are present. IFA gives an antibody titer that is useful for comparison in sequential testing and should contain an internal negative control at each dilution. RT-PCR detects the RNA of the FCoV. Detection of FCoV RNA in the blood or feces is not diagnostic of FIP, since many healthy animals or animals with non-FIP illness are also positive. Fecal RT-PCR is most useful in FCoV control as part of a series of tests; a single negative or positive test is usually meaningless. Determination of carrier cats requires nine monthly consecutive positive

Box  286-2 Protocol for Prevention of Feline Coronavirus Infection in Kittens • Prepare kitten room • Remove all cats and kittens 1 week before introducing queen. • Disinfect room as far as possible using 1:32 dilution of sodium hypochlorite. • Dedicate litter trays, food and water bowls to this room and disinfect with sodium hypochlorite. • Introduce queen 1-2 weeks before she is due to give birth. • Practice barrier nursing • Deal with the kitten room before tending other cats. • Clean hands with disinfectant before going into kitten room. • Have shoes and coveralls dedicated to the kitten room. • Wean and isolate kittens early • Test queen for FCoV antibodies either before or after kittening. • If queen’s antibody titer is greater than zero, the kittens should be removed to another clean room when they are 5-6 weeks old. • If the queen has an antibody titer of zero, she can remain with the kittens until they are older. • Take care to socialize isolated kittens to accustom them to humans during the 2-7–week-old period. • Test kittens • Test kittens for FCoV antibodies at over 10 weeks of age. FCoV, Feline coronavirus.

fecal RT-PCR tests (this may change as quantitative RTPCR becomes more widely available). Determination that a cat has eliminated FCoV infection requires five consecutive negative fecal RT-PCR tests or the return of the cat’s antibody titer to less than 10.

Prevention of the Seropositive Cat From Developing Feline Infectious Peritonitis Approximately 1 cat in 10 infected with FCoV develops FIP. Cats that have FCoV antibodies should not be stressed if at all possible (e.g., they should not be rehomed; neutering or any other operation that is not lifesaving should be delayed). If the owner has to leave the seropositive cat, having a “cat sitter” look after the cats in their own home is preferable to putting the cats into a cattery.

Feline Parvovirus, Feline Panleukopenia, Feline Infectious Enteritis, Canine Parvovirus It is tempting to assume that feline parvovirus (FPV) (feline panleukopenia, feline infectious enteritis) is an infection of the past that has been more or less eradicated by vaccination. However, outbreaks are still ubiquitous wherever there are groups of susceptible cats and often manifest as sudden death or acute illness. FPV is the major cause of death of kittens under 4 months of age in rescue and breeding catteries and pet shops in the United Kingdom (Cave et al, 2002). Unlike FPV, which has been recognized in cats for at least 100 years, canine parvovirus (CPV) type 2 emerged suddenly in the 1970s. CPV2 was subsequently replaced by antigenically variant viruses (CPV2a and CPV2b), which now coexist in dog populations worldwide. CPV2 isolates did not replicate in cats, but both CPV2a and CPV2b will. In a Japanese study about 10% of the virus isolates from cats with feline enteritis were found to be CPV2a or CPV2b. A third strain, CPV2c, isolated from leopard cats, can also infect domestic cats. Surprisingly, only 30% of parvoviruses from cheetahs and other large cats in zoos were FPV; the others were CPV. Parvovirus is shed in feces but is also present in other secretions and can survive up to a year in the environment. Transmission of parvoviruses is mainly indirect; transplacental transmission also occurs. Despite the good acceptance of excellent vaccines by the cat-owning community, parvovirus manages to avoid extinction by subclinically infecting susceptible cats and kittens in whom it replicates. These cats shed huge amounts of viral particles for a few days to possibly weeks so that the environment becomes recontaminated. The virus can be transported on shoes or in cats’ baskets to contaminate new environments so that even cats kept permanently indoors are not safe from infection. Thus cats in all types of catteries should be vaccinated. Live vaccines should not be used in pregnant queens because the virus can infect unborn kittens. Attenuated live and inactivated vaccines are available against FPV and protect against both FPV and CPV2a, CPV2b, and CPV2c, but protection of inactivated vaccines is weaker against CPV types than against FPV. Most

manufacturers recommend vaccination from 8 weeks of age onward, with a second dose at 12 weeks. A booster at 1 year of age is essential to cover cats in which the initial course was ineffective because of the presence of MDA. MDA can persist until almost 20 weeks of age in kittens, particularly in those born to naturally exposed mothers who have very high antibody titers that interfere with vaccination and leave apparently vaccinated kittens susceptible to FPV. This is a problem in breeding catteries. Annual boosters are recommended by the manufacturer, but other than the first year, vaccination may not be absolutely necessary. There is evidence to suggest that immunity may persist; nine cats that were vaccinated with an inactivated FPV vaccine, kept in isolation, and given no boosters were challenged 7.5 years later and all still appeared to be immune (Scott and Geissinger, 1999). When colostrum is not available, vaccination of newborn kittens is possible, and neutralizing antibodies appear at 7 to 12 days of age, indicating protection. However, live vaccines should not be used in kittens under 4 weeks of age or in pregnant queens because of the risk of cerebellar hypoplasia. Since FPV may only be shed for a matter of hours (sometimes as little as 36 hours), detection of the virus itself in cat feces is of limited value, and direct detection of FPV in the environment is currently not possible. Antibody testing of the sick cat can be more useful than detection of the virus itself. Antibodies to FPV can be detected by hemagglutination inhibition and enzymelinked immunosorbent assay tests. For postmortem diagnosis of FPV, three 1-cm sections of different levels of the small intestine (duodenum, jejunum, and ileum) in 10% formol saline should be sent to a laboratory for ­histopathologic examination.

Advice for Rescue and Breeding Catteries and Pet Shops Once parvovirus has occurred on the premises, the virus can be present for at least a year. Disinfection is difficult, with parvovirus resisting many disinfectants. Parvovirus is killed by sodium hypochlorite (domestic bleach). Disinfection with sodium hypochlorite (diluted 1:32) can reduce virus dose but will not eliminate the virus from soft furnishings. Since bleach is inactivated by organic material, thorough cleaning beforehand is vital for the success of disinfection. It is important to realize that infection is maintained in premises by subclinical infection of susceptible animals that become infected, produce huge amounts of virus, and then recover. Therefore susceptible animals are at risk if introduced within a year, and any new animals should have had a full course of vaccination, completed at least a week before being introduced. To establish whether a cattery has parvovirus, some of the breeding animals should be tested for antibodies.

Chapter  286  Control of Viral Diseases in Catteries

1305

Antibody titers will be much higher in naturally exposed cats than in vaccinated cats. One option to prevent parvovirus is to stop breeding for a year so that no susceptible kittens are introduced. Kittens are protected from parvovirus by MDA. The time over which antibody wanes can be calculated by halving the mother’s antibody titer every 9.5 days of the offspring’s life (97% of the queen’s titer is found in the kitten). Thus if a queen had an antibody titer of 1024, at 9.5 days old the kitten’s titer would be approximately 512, at 19 days 256, at 28.5 days 128, and so on (providing the kitten had suckled colostrum adequately). In this example, the kitten’s titer would be 32 at 47.5 days. Thus the kitten should be rehomed to a parvovirus-free environment at that stage and vaccinated when its antibody titer has fallen to less than 10. Further vaccination of adult breeding stock is often pointless since many cats have a very high naturally acquired immunity, but it may be useful to screen all the breeding stock for antibodies and boost any cats that have very low antibody titers using a live vaccine (or inactivated vaccine if the cat is pregnant).

References and Suggested Reading Cave TA et al: Kitten mortality in the United Kingdom: a retrospective analysis of 274 histopathological examinations (19862000), Vet Rec 151:497, 2002. Chandler EA, Gaskell CJ, Gaskell RM, editors: Feline medicine and therapeutics, Oxford, Blackwell Science. Coyne KP et al: Lethal outbreak of disease associated with feline calicivirus infection in cats, Vet Rec 158:544, 2006. Green CE, editor: Infectious diseases of the dog and cat, ed 3, Philadelphia, 2006, Saunders. Maggs DJ: Update on the diagnosis and management of feline herpesvirus-1 infection. In August JR, editor: Consultations in feline internal medicine, vol 4, Philadelphia, 2001, Saunders, p 51. Pesavento PA et al: Pathologic, immunohistochemical, and electron microscopic findings in naturally occurring virulent systemic feline calicivirus infection in cats, Vet Pathol 41:257, 2004. Radford AD et al: Quasispecies evolution of a hypervariable region of the feline calicivirus capsid gene in cell culture and in persistently infected cats, J Gen Virol 79:1, 1998. Radford AD et al: Feline calicivirus, Vet Res 38:319, 2007. Scott FW, Geissinger CM: Long-term immunity in cats vaccinated with an inactivated trivalent vaccine, Am J Vet Res 60:652, 1999. Published erratum appears in Am J Vet Res 60:763, 1999. Available at http://www.catvirus.com for FCoV.

Websites Addie DD: www.catvirus.com www.sheltermedicine.com

Appendix 

I

Table of Common Drugs:   Approximate Dosages Mark G. Papich, Consulting Editor

Drug Name

Other Names

Formulations Available

Dosage

Acepromazine

PromAce and many generic brands

5-, 10-, and 25-mg tablets and 10-mg/ml injection

Dog: 0.02-0.1 mg/kg IM, SC, IV; 0.56-2.25 mg/kg PO q6-8hr Cat: 0.02-0.1 mg/kg IM, SC, IV; or 1-2 mg/kg PO q8-12hr

Acetaminophen

Tylenol and many generic brands

120-, 160-, 325-, and 500-mg tablets

Dog: 15 mg/kg PO q8hr Cat: Not recommended

Acetaminophen with codeine

Tylenol with codeine and many generic brands

Oral solution and tablets. Many forms Follow dosing recommendations for (e.g., 300 mg acetaminophen plus codeine either 15, 30, or 60 mg codeine)

Acetazolamide

Diamox

125- and 250-mg tablets

5-10 mg/kg PO q8-12hr (glaucoma) 4-8 mg/kg PO q8-12hr (other diuretic uses)

Acetylcysteine

Mucomyst

20% solution

Antidote: 140 mg/kg (loading dose) then 70 mg/kg IV or PO q4hr for five doses Eye: 2% solution topically q2hr

Acetylsalicylic acid

See Aspirin

ACTH

See Corticotropin

Activated charcoal

See Charcoal, activated

Adequan

See Polysulfated glycosaminoglycan (PSGAG)

Albendazole

Valbazen

113.6-mg/ml suspension and 300-mg/ml paste

25-50 mg/kg PO q12hr for 3 days For Giardia use 25 mg/kg q12hr for 2 days

Albuterol

Proventil or Ventolin

2-, 4-, and 5-mg tablets; 2 mg/5 ml syrup

20-50 mcg/kg q6-8hr; up to maximum of 100 mcg/kg q6-8hr PO

Allopurinol

Lopurin, Zyloprim

100- and 300-mg tablets

10 mg/kg q8hr, then reduce to 10 mg/kg q24hr

Aluminum carbonate gel

Basalgel

Capsule (equivalent to 500 mg aluminum hydroxide)

10-30 mg/kg PO q8hr (with meals)

Aluminum hydroxide gel

Amphojel

64-mg/ml oral suspension; 600-mg tablet

10-30 mg/kg PO q8hr (with meals)

Amikacin

Amiglyde-V (veterinary) and Amikin (human)

50- and 250-mg/ml injection

Dog: 15-30 mg/kg IV, SC, IM q24hr Cat: 10-14 mg/kg IV, SC, IM q24hr

Amiodarone

Cordarone

200-mg tablets; 50-mg/ml injection

Dog: Start with 15-mg/kg loading dose, then 10 mg/kg/day thereafter

Aminopentamide

Centrine

0.2-mg tablet; 0.5-mg/ml injection

Dog: 0.01-0.03 mg/kg IM, SC, PO q8-12hr Cat: 0.1 mg/cat IM, SC, PO q8-12hr

1306

Appendix  I  Table of Common Drugs: Approximate Dosages



1307

Drug Name

Other Names

Formulations Available

Dosage

Aminophylline

Many (generic) (Theophylline is preferred for oral therapy)

100- and 200-mg tablets; 25-mg/ml injection

Dog: 10 mg/kg PO, IM, IV q8hr Cat: 6.6 mg/kg PO q12hr

6-Aminosalicylic acid

See Mesalamine, Olsalazine

Amitraz

Mitaban

10.6-ml concentrated dip (19.9%)

10.6 ml per 7.5 L water (0.025% ­solution). Apply three to six topical treatments q2wk. For refractory cases, this dose has been exceeded to produce increased efficacy. Doses that have been used include 0.025%, 0.05%, and 0.1% ­concentration applied twice per week and 0.125% solution applied to one-half body every day for 4 weeks to 5 months.

Amitriptyline

Elavil

10-, 25-, 50-, 75-, 100-, and 150-mg tablets; 10-mg/ml injection

Dog: 1-2 mg/kg PO q12-24hr (range: 0.25-4 mg/kg q12-24hr) Cat: 2-4 mg/cat/day PO; for cystitis: 2 mg/kg/day (2.5-7.5 mg/cat/day)

Amlodipine besylate

Norvasc

2.5-, 5-, and 10-mg tablets

Dog: 2.5 mg/dog or 0.1 mg/kg PO once daily Cat: 0.625 mg/cat/day PO initially and increase if needed to 1.25 mg/cat/day (average is 0.18 mg/kg)

Ammonium chloride

Generic

Available as crystals

Dog: 100 mg/kg PO q12hr Cat: 800 mg/cat (approximately 1⁄3 to ¼ tsp) mixed with food daily

Amoxicillin trihydrate

Amoxi-Tabs, Amoxi-drops, Amoxil, and others

50-, 100-, 200-, and 400-mg tablets; 50-mg/ml oral suspension

6.6-20 mg/kg PO q8-12hr

Amoxicillin/clavulanic acid

Clavamox

62.5-, 125-, 250-, and 375-mg tablets; 62.5-mg/ml suspension

Dog: 12.5-25 mg/kg PO q12hr Cat: 62.5 mg/cat PO q12hr; consider administering these doses q8hr for gram-negative infections

Amphotericin B

Fungizone

50-mg injectable vial

0.5 mg/kg IV (slow infusion) q48hr, to a cumulative dose of 4-8 mg/kg

Amphotericin B (Liposomal)

Amphotec, Abelcet, AmBisome

Ampicillin

Omnipen, Principen, others

250-, and 500-mg capsules; 125-, 250-, and 500-mg vials of ampicillin sodium

10-20 mg/kg IV, IM, SC q6-8hr (ampicillin sodium) 20-40 mg/kg PO q8hr

Ampicillin + sulbactam

Unasyn

1.5- and 3-gm vials in 2:1 combination for injection

10-20 mg/kg IV, IM q8hr

Ampicillin trihydrate

Polyflex

10- and 25-mg vials for injection

Dog: 10-50 mg/kg SC, IM q24hr Cat: 10-20 mg/kg SC, IM q24hr

Amprolium

Amprol, Corid

9.6% (9.6 gm/dl) oral solution; soluble powder

1.25 gm of 20% amprolium ­powder to daily feed, or 30 ml of 9.6% ­amprolium solution to 3.8 L of drinking water for 7 days

Antacid drugs

See Aluminum hydroxide gel, Magnesium hydroxide, and Calcium carbonate

Apomorphine hydrochloride

Generic

6-mg tablet

0.44 mg/kg IM; 0.05 mg/kg IV; 0.1 mg/kg SC, or instill 0.25 mg in conjunctiva of eye (dissolve 6-mg tablet in 1-2 ml of saline)

Ascorbic acid

Vitamin C

Various forms

100-500 mg/animal/day (diet ­supplement) or 100 mg/animal q8hr (urine acidification)

Dog: 2-3 mg/kg IV 3 times/wk for 9-12 treatments for a cumulative dose of 24-27 mg/kg Cat: 1 mg/kg IV 3 times/wk for 12 treatments

Continued

1308

Appendix  I  Table of Common Drugs: Approximate Dosages

Appendix I—cont’d Drug Name

Other Names

Formulations Available

Dosage

l-Asparaginase

Elspar

10,000 U per vial for injection

400 U/kg IV, IP, IM weekly; or 10,000 U/m2 weekly for 3 wk

Aspirin

Many generic and brand names (Bufferin, Ascriptin)

81-mg and 325-mg tablets

Dog: Mild analgesia: 10 mg/kg q12hr Antiinflammatory: 20-25 mg/kg q12hr Antiplatelet: 5-10 mg/kg q24-48hr Cat: 81 mg q48hr PO

Atenolol

Tenormin

25-, 50-, and 100-mg tablets; 25-mg/ml oral suspension; and 0.5-mg/ml ampule for injection

Dog: 6.25-12.5 mg/dog q12hr (or 0.25-1.0 mg/kg q12-24hr) PO Cat: 6.25-12.5 mg/cat q12hr (approximately 3 mg/kg) PO

Atipamezole

Antisedan

5-mg/ml injection

Inject same volume as used for medetomidine

Atracurium

Tracrium

10-mg/ml injection

0.2 mg/kg IV initially, then 0.15 mg/kg q30min (or IV infusion at 4-9 mcg/kg/min)

Atropine

Many generic brands

400-, 500-, and 540-mcg/ml injection; 15-mg/ml injection

0.02-0.04 mg/kg IV, IM, SC q6-8hr 0.2-0.5 mg/kg (as needed) for organophosphate and carbamate toxicosis

Auranofin (triethyl­ phosphine gold)

Ridaura

3-mg capsule

0.1-0.2 mg/kg PO q12hr

Aurothioglucose

Solganol

50-mg/ml injection

Dog 10 kg: 5 mg IM first wk, 10 mg IM second wk, 1 mg/kg/wk maintenance Cat: 0.5-1 mg/cat IM q7 days

Azathioprine

Imuran

50-mg tablet; 10-mg/ml for injection

Dog: 2 mg/kg PO q24hr initially then 0.5-1 mg/kg q48hr Cat (use cautiously): 0.3 mg/kg PO q48hr

Azithromycin

Zithromax

250-mg capsule; and 250- and 600-mg tablets; 20-mg/ml oral suspension

Dog: 10 mg/kg PO q48hr or 3.3 mg/kg once daily Cat: 5-10 mg/kg PO every other day

AZT (azidothymidine)

See Zidovudine

Bactrim (sulfamethoxa- See Trimethoprim-sulfonamide combinations zole + trimethoprim) BAL

See Dimercaprol

Benazepril

Lotensin

5-, 10-, 20-, and 40-mg tablets

Dog: 0.25-0.5 mg/kg PO q24hr Cat: 0.5-1 mg/kg q24hr PO or 2.5 mg/cat/day up to a maximum of 5 mg/cat/day

Betamethasone

Celestone

600-mcg (0.6-mg) tablet; 3-mg/ml sodium phosphate injection

0.1-0.2 mg/kg PO q12-24hr

Bethanechol

Urecholine

5-, 10-, 25-, and 50-mg tablets; 5-mg/ml injection

Dog: 5-15 mg/dog PO q8hr Cat: 1.25-5 mg/cat PO q8hr

Bisacodyl

Dulcolax

5-mg tablet

5 mg/animal PO q8-24hr

Bismuth subsalicylate

Pepto Bismol

Oral suspension: 262 mg/15 ml or 525 mg/ml in extra-strength formulation; 262-mg tablet

1-3 ml/kg/day (in divided doses) PO

Bleomycin

Blenoxane

15-U vials for injection

10 U/m2 IV or SC for 3 days, then 10 U/m2 weekly (maximum cumulative dose 200 U/m2)

Bromide

See Potassium bromide

Appendix  I  Table of Common Drugs: Approximate Dosages



Drug Name

Other Names

BSP (Bromsulphalein)

See Sulfobromophthalein (BSP)

Budesonide

1309

Formulations Available

Dosage

Enterocort

3-mg capsule

Dog, cat: 0.125 mg/kg q6-8hr PO; dose interval may be increased to every 12 hr when condition improves

Bunamidine hydrochloride

Scolaban

400-mg tablet

20-50 mg/kg PO

Bupivacaine

Marcaine and generic

2.5- and 5-mg/ml solution injection

1 ml of 0.5% solution per 10 cm for an epidural

Buprenorphine

Temgesic (Vetergesic in the UK)

0.3-mg/ml solution

Dog: 0.006-0.02 mg/kg IV, IM, SC q4-8hr Cat: 0.005-0.01 mg/kg IV, IM q4-8hr Buccal administration in cats: 0.01-0.02 mg/kg q12hr

Buspirone

BuSpar

5- and 10-mg tablets

Dog: 2.5-10 mg/dog PO q12-24hr; or 1 mg/kg q12hr PO Cat: 2.5-5 mg/cat PO q24hr (may be increased to 5-7.5 mg/cat twice daily for some cats)

Busulfan

Myleran

2-mg tablet

3-4 mg/m2 PO q24hr

Butorphanol

Torbutrol Torbugesic

1-, 5-, and 10-mg tablets; 0.5- or 10-mg/ml injection

Dog: Antitussive: 0.055 mg/kg SC q6-12hr or 0.55 mg/kg PO ­Preanesthetic: 0.2-0.4 mg/kg IV, IM, SC (with acepromazine) Analgesic: 0.2-0.4 mg/kg IV, IM, SC q2-4hr or 0.55-1.1 mg/kg PO q6-12hr Cat: Analgesic: 0.2-0.8 mg/kg IV, SC q2-6hr, or 1.5 mg/kg PO q4-8hr

Calcitriol

Rocaltrol, Calcijex

Available as injection (Calcijex) and capsules (Rocaltrol): 0.25- and 0.5-mcg capsules; 1- or 2-mcg/ml injection

Dog: 0.25-0.5 mcg/dog/day or approx. 0.12 mg/kg Cat: 0.25 mcg/cat every other day; or 0.01-0.04 mcg/kg/day

Calcium carbonate

Many brands available: Titralac, Tums, generic

Many tablets or oral suspension (e.g., 650-mg tablet contains 260 mg calcium ion)

For phosphate binder: 60-100 mg/kg/day in divided doses PO For calcium supplementation: 70-180 mg/kg/day added to food

Calcium chloride

Generic

10% (100 mg/ml) solution

0.1-0.3 ml/kg IV (slowly)

Calcium citrate

Citracal (OTC)

950-mg tablet (contains 200 mg calcium ion)

Dog: 20 mg/kg/day added to food Cat: 10-30 mg/kg PO q8hr (with meals)

Calcium disodium EDTA

See Edetae calcium disodium

Calcium gluconate

Kalcinate and generic

10% (100 mg/ml) injection

0.5-1.5 ml/kg IV (slowly)

Calcium lactate

Generic

OTC tablet

Dog: 0.5-2.0 gm/dog/day PO (in divided doses) Cat: 0.2-0.5 gm/cat/day PO (in divided doses)

Captopril

Capoten

25-mg tablet

Dog: 0.5-2 mg/kg PO q8-12hr Cat: 3.12-6.25 mg/cat PO q8hr

Carbenicillin

Geopen, Pyopen

1-, 2-, 5-, 10-, and 30-gm vials for injection

40-50 mg/kg and up to 100 mg/kg IV, IM, SC q6-8hr

Carbenicillin indanyl sodium

Geocillin

500-mg tablet

10 mg/kg PO q8hr

Carbimazole

Neo-mercazole

Available in Europe

Cat: 5 mg/cat PO q8hr (induction), followed by 5 mg/cat PO q12hr

Carboplatin

Paraplatin

50- and 150-mg vial for injection

Dog: 300 mg/m2 IV q3-4wk Cat: 200 mg/m2 IV q4wk Continued

1310

Appendix  I  Table of Common Drugs: Approximate Dosages

Appendix I—cont’d Drug Name

Other Names

Formulations Available

Dosage

Carprofen

Rimadyl (Zinecarp in the UK) Novox (generic)

25-, 75-, and 100-mg tablets 50 mg/ml solution

Dog: 2.2 mg/kg PO q12hr; or 4.4 mg/kg once daily PO; 2.2 mg/kg q12hr or 4.4 mg/kg once daily SC Cat: doses not available

Carvedilol

Coreg

3.125-, 6.25-, 12.5-, and 25-mg tablets

Dog: 0.2 to 0.4  mg/kg q12hr PO; titrate dose up to 1.5  mg/kg q12hr PO if needed

Cascara sagrada

Many brands (e.g., Nature’s Remedy)

100- and 325-mg tablets

Dog: 1-5 mg/kg day PO Cat: 1-2 mg/cat/day

Castor oil

Generic

Oral liquid (100%)

Dog: 8-30 ml/day PO Cat: 4-10 ml/day PO

Cefadroxil

Cefa-Tabs, Cefa-Drops

50-mg/ml oral suspension; 50-, 100-, 200-, and 1000-mg tablets

Dog: 22-30 mg/kg PO q12hr Cat: 22 mg/kg PO q24hr

Cefazolin sodium

Ancef, Kefzol, and generic

50 and 100 mg/50 ml for injection

20-35 mg/kg IV, IM q8hr For ­perisurgical use: 22 mg/kg q2hr during surgery

Cefdinir

Omnicef

300-mg capsules; 25-mg/ml oral suspension

Dose not established (human dose is 7 mg/kg PO q12hr)

Cefixime

Suprax

20-mg/ml oral suspension and 200- and 400-mg tablets

10 mg/kg PO q12hr For cystitis: 5 mg/kg PO q12-24hr

Cefotaxime

Claforan

500-mg and 1-, 2-, and 10-gm vials for injection

Dog: 50 mg/kg IV, IM, SC q12hr Cat: 20-80 mg/kg IV, IM q6hr

Cefotetan

Cefotan

1-, 2-, and 10-gm vials for injection

30 mg/kg IV, SC q8hr

Cefovecin

Convenia

80 mg/ml injection

Dog, cat: 8 mg/kg SC once every 14 days

Cefoxitin sodium

Mefoxin

1-, 2-, and 10-gm vials for injection

30 mg/kg IV q6-8hr

Cefpodoxime proxetil

Simplicef

100- and 200-mg tablets; 10- or 20-mg/ml human label suspension

Dog: 5-10 mg/kg PO once daily Cat: Dose not established

Ceftazidime

Fortaz, Ceptaz, Tazicef

0.5-, 1-, 2- and 6-gm vials reconstituted to 280 mg/ml

30 mg/kg IV, IM q6hr

Ceftiofur

Naxcel (ceftiofur sodium); Excenel (ceftiofur HCl)

50-mg/ml injection

2.2-4.4 mg/kg SC q24hr (for urinary tract infections)

Cephalexin

Keflex and generic forms

250- and 500-mg capsules; 250- and 500-mg tablets; 100-mg/ml or 125- and 250-mg/5-ml oral suspension

10-30 mg/kg PO q6-12hr; for pyoderma, 22-35 mg/kg PO q12hr

Cetirizine

Zyrtec

1-mg/ml oral syrup; 5- and 10-mg tablets

Dog: 5-10  mg/dog q12hr, PO, up to a dose of 2 mg/kg q12hr, PO Cat: 5 mg/cat, PO, q24hr

Charcoal, activated

ActaChar, Charcodote, Toxiban, generic

Oral suspension

1-4 gm/kg PO (granules) 6-12 ml/kg (suspension)

Chlorambucil

Leukeran

2-mg tablet

Dog: 2-6 mg/m2 or 0.1-0.2 mg/kg PO q24hr initially, then q48hr Cat: 0.1-0.2 mg/kg q24hr initially, then q48hr PO

Chloramphenicol and chloramphenicol palmitate

Chloromycetin, generic forms

30-mg/ml oral suspension (palmitate); 250-mg capsule; and 100-, 250-, and 500-mg tablets

Dog: 40-50 mg/kg PO q8hr Cat: 12.5-20 mg/kg PO q12hr

Chlorothiazide

Diuril

250- and 500-mg tablets; 50-mg/ml oral suspension and injection

20-40 mg/kg PO q12hr or IV

Chlorpheniramine maleate

Chlor-Trimeton, Phenetron, and others

4- and 8-mg tablets

Dog: 4-8 mg/dog PO q12hr (up to a maximum of 0.5 mg/kg q12hr) Cat: 2 mg/cat PO q12hr

Chlorpromazine

Thorazine

25-mg/ml injection solution

Dog: 0.5 mg/kg IM, SC q6-8hr (before ­cancer chemotherapy administer 2 mg/kg SC q3hr) Cat: 0.2-0.4 mg/kg q6-8hr IM, SC

Appendix  I  Table of Common Drugs: Approximate Dosages



Drug Name

Other Names

Chorionic gonadotropin

See Gonadotropin

Cimetidine

1311

Formulations Available

Dosage

Tagamet (OTC and prescription)

100-, 150-, 200-, and 300-mg tablets and 60-mg/ml injection

10 mg/kg IV, IM, PO q6-8hr (in renal failure administer 2.5-5 mg/kg IV, PO q12hr)

Ciprofloxacin

Cipro and generic

250-, 500-, and 750-mg tablets; 2-mg/ml injection

Dog: 10-20 mg/kg PO, IV q24hr Cat: Not recommended

Cisapride

Must be compounded

Cisplatin

Platinol

Clavamox

See Amoxicillin-clavulanic acid combination

Clavulanic acid

See Amoxicillin-clavulanic acid combination

Clemastine

Tavist, Contac 12-hr allergy, and generic

1.34-mg tablet (OTC); 2.64-mg tablet (Rx); 0.134-mg/ml syrup

Dog: 0.05-0.1 mg/kg PO q12hr

Clindamycin

Antirobe, Cleocin, and generic

Oral liquid 25-mg/ml; 25-, 75-, 150-, and 300-mg capsule; and 150-mg/ml injection (Cleocin)

Dog: 11-33 mg/kg q12hr PO; for oral and soft tissue infection: 5.5-33 mg/kg q12hr PO Cat: 11-33 mg/kg q24hr PO for skin and anaerobic infections­ Toxoplasmosis: 12.5-25 mg/kg PO q12hr for 4 wks

Clofazimine

Lamprene

50- and 100-mg capsules

Cat: 1 mg/kg PO up to a maximum of 4 mg/kg/day

Clomipramine

Anafranil (human label); Clomicalm (veterinary label)

10-, 25-, and 50-mg tablets (human) 5-, 20-, and 80-mg tablets (veterinary)

Dog: 1-2 mg/kg PO q12hr up to a maximum of 3 mg/kg PO q12hr Cat: 1-5 mg/cat PO q12-24hr

Clonazepam

Klonopin

0.5-, 1-, and 2-mg tablets

Dog: 0.5 mg/kg PO q8-12hr Cat: 0.1-0.2 mg/kg q12-24hr PO

Clopidogrel

Plavix

75-mg tablets

Dog: 2-4 mg/kg q24hr PO; give oral loading dose of 10  mg/kg Cat: 19  mg per cat (¼ tablet) q24hr PO

Clorazepate

Tranxene

3.75-, 7.5-, 11.25-, 15-, and 22.5-mg, tablets

Dog: 2 mg/kg PO q12hr Cat: 0.2-0.4 mg/kg q12-24hr PO (up to 0.5-2 mg/kg)

Cloxacillin

Cloxapen, Orbenin, Tegopen

250- and 500-mg capsules; 25-mg/ml oral solution

20-40 mg/kg PO q8hr

Codeine

Generic

15-, 30-, and 60-mg tablets; 5-mg/ml syrup; 3-mg/ml oral solution

Analgesia: 0.5-1 mg/kg PO q4-6hr Antitussive: 0.1-0.3 mg/kg PO q4-6hr

Colchicine

Generic

500- and 600-mcg tablets; 500-mcg/ml ampule injection

0.01-0.03 mg/kg PO q24hr

Colony-stimulating factor

Sargramostim (Leukine) and Filgrastim (Neupogen)

300 mcg/ml (Neupogen) and 250 or 500 mcg/ml (Leukine)

Leukine: 0.25  mg/m2 q12hr SC or IV infusion Neupogen: 0.005  mg/kg (5  mcg/kg) q24 hr SC for 2 wk

Corticotropin (ACTH)

Acthar

Gel 80 U/ml

Response test: Collect pre-ACTH ­ sample and inject 2.2 IU/kg IM; collect post-ACTH sample in 2 hr in dogs and at 1 and 2 hr in cats

Dog: 0.1-0.5 mg/kg PO q8-12hr (doses as high as 0.5-1.0 mg/kg have been used in some dogs) Cat: 2.5-5 mg/cat PO q8-12hr (as high as 1 mg/kg q8hr has been ­administered to cats) 1-mg/ml injection; 50-mg vials

Dog: 60-70 mg/m2 q3-4wk (administer fluid for diuresis with therapy) Cat: Not recommended

Continued

1312

Appendix  I  Table of Common Drugs: Approximate Dosages

Appendix I—cont’d Drug Name

Other Names

Formulations Available

Dosage

Cosequin

See Glucosamine chondroitin sulfate

Cosyntropin

Cortrosyn

250 mcg per vial (can be stored in freezer for 6 months)

Response test: Dog: Collect pre-ACTH ­sample and inject 5 mcg/kg IV or IM and collect sample at 30 and 60 min Cat: 0.125 mg IV or IM and collect sample at 30 min and 60 min after IV administration and 30 and 60 min after IM administration

Cyanocobalamin (vitamin B12)

Many

100-mcg/ml injection

Dog: 100-200 mcg/day PO Cat: 50-100 mcg/day PO

Cyclophosphamide

Cytoxan, Neosar

25-mg/ml injection; 25- and 50-mg tablets

Dog: Anticancer: 50 mg/m2 PO once daily 4 days/wk or 150-300 mg/m2 IV and repeat in 21 days Immunosuppressive therapy: 50 mg/m2 (approx. 2.2 mg/kg) PO q48hr or 2.2 mg/kg once daily for 4 days/wk Cat: 6.25-12.5 mg/cat once daily 4 days/wk

Cyclosporine (cyclosporin A)

Atopica, Neoral, Optimmune (ophthalmic)

Atopica: 10-, 25-, 50-, and 100-mg capsules Neoral: 25-mg and 100-mg microemulsion capsules; 100-mg/ml oral solution (for microemulsion) Optimmune: 0.2% ointment

Dog: 3-7 mg/kg/day; for atopic dermatitis some dogs are controlled with q48hr dosing Cat: 5 mg/kg PO q24hr

Cyropheptadine

Periactin

4-mg tablet; 2-mg/5-ml syrup

Antihistamine: 1.1 mg/kg PO q8-12hr Appetite stimulant: 2 mg/cat PO

Cytarabine (cytosine arabinoside)

Cytosar-U

100-mg vial

Dog (Iymphoma): 100 mg/m2 IV, SC once daily or 50 mg/m2 twice daily for 4 days Cat: 100 mg/m2 once daily for 2 days

Dacarbazine

DTIC

200-mg vial for injection

200 mg/m2 IV for 5 days q3wk; or 800-1000 mg/m2 IV q3wk

Dalteparin

Fragmin

16 mg/0.2  ml; 32  mg/0.2  ml in prefilled syringes or 64  mg/ml multidose vials for injection

Dog: 100-150 units/kg q8hr SC Cat: 180 units/kg q6hr SC

Danazol

Danocrine

50-, 100-, and 200-mg capsules

5-10 mg/kg PO q12hr

Dantrolene

Dantrium

100-mg capsule and 0.33-mg/ml injection

For prevention of malignant ­hyperthermia: 2-3 mg/kg IV For muscle relaxation: Dog: 1-5 mg/kg PO q8hr Cat: 0.5-2 mg/kg PO q12hr

Dapsone

Generic

25- and 100-mg tablets

Dog: 1.1 mg/kg PO q8-12hr Cat: Do not use

Darbazine (prochlorperazine + isopropamide)

Darbazine

No. 1, 2, and 3 capsules

Dog, cat: 0.14-0.2 ml/kg SC q12hr Dog 2-7 kg: 1-#1 capsule PO q12hr Dog 7-14 kg: 1-#2 capsule PO q12hr Dog >14 kg: 1-#3 capsule PO q12hr

Deferoxamine

Desferal

500-mg vial for injection

10 mg/kg IV, IM q2hr for two doses; then 10 mg/kg q8hr for 24hr

Deprenyl (l-deprenyl)

See Selegiline (Anipryl)

Deracoxib

Deramaxx

25-, 100-mg tablets

Dog: 3-4  mg/kg q24hr PO for 7 days; or 1-2  mg/kg q24hr PO for long-term use Cat: Dose not established

Appendix  I  Table of Common Drugs: Approximate Dosages



1313

Drug Name

Other Names

Formulations Available

Dosage

Desmopressin acetate

DDAVP

100-mcg/ml injection and ­desmopressin acetate nasal solution (0.01% metered spray); 0.1- and 0.2-mg tablets

Diabetes insipidus: 2-4 drops (2 mcg) q12-24hr intranasally or in eye Animal oral dose: 0.05-0.1 mg/dog q12hr PO initially, then increase to 0.1-0.2 mg/dog q12hr as needed von Willebrand’s disease treatment: 1 mcg/kg (0.01 ml/kg) SC, IV, diluted in 20 ml of saline administered over 10 min

Desoxycorticosterone pivalate

Percorten-V, DOCP, or DOCA pivalate

25 mg/ml injection

1.5-2.2 mg/kg IM q25days

Dexamethasone (dexamethasone solution and dexamethasone sodium phosphate)

Azium solution in polyethylene glycol. Sodium phosphate forms include Dexaject SP, Dexavet, and Dexasone. Tablets include Decadron and generic

Azium solution, 2 mg/ml. Sodium phosphate forms are 3.33 mg/ml; 0.25-, 0.5-, 0.75-, 1-, 1.5-, 2-, 4-, and 6-mg tablets

Antiinflammatory: 0.07-0.15 mg/kg IV, IM, PO q12-24hr Dexamethasone suppression test: Dog: 0.01 mg/kg IV Cat: 0.1 mg/kg IV Collect sample at 0, 4, and 8 hr

Dexmedetomidine

Dexdomitor

0.5-mg/ml injectable solution

Dog: Sedative and analgesic: 375 mg/m2 IV or 500  mg/m2 IM Dog: Preanesthetic: 125 mg/m2 IM Cat: Sedative and analgesic: 40  mcg/kg IM

Dextran

Dextran 70 Gentran-70

Injectable solution: 250, 500, and 1000 ml

10-20 ml/kg IV to effect

Dextromethorphan

Benylin and others

Available in syrup, capsule, and tablet; many OTC products

0.5-2 mg/kg PO q6-8hr has been reported, but effective dose not established

Dextrose solution 5%

D5W

Fluid solution for IV administration

40-50 ml/kg IV q24hr

Diazepam

Valium and generic

2- and 5-mg tablets; 5-mg/ml solution for injection

Preanesthetic: 0.5 mg/kg IV Status epilepticus: 0.5 mg/kg IV, 1.0 mg/kg rectal; repeat if necessary Appetite stimulant (cat): 0.2 mg/kg IV

Dichlorophen

Vermiplex (See Toluene)

Dichlorphenamide

Daranide

50-mg tablet

3-5 mg/kg PO q8-12hr

Dichlorvos

Task

10- and 25-mg tablets

Dog: 26.4-33 mg/kg PO Cat: 11 mg/kg PO

Dicloxacillin

Dynapen

125-, 250-, and 500-mg capsules; 12.5-mg/ml oral suspension

25 mg/kg IM q6hr Oral doses not absorbed

Diethylcarbamazine (DEC)

Caricide, Filaribits

Chewable tablets; 50-, 60-, 180-, 200-, and 400-mg tablets

Heartworm prophylaxis: 6.6 mg/kg PO q24hr

Diethylstilbestrol (DES)

DES, generic (no longer manufactured in US)

1- and 5-mg tablet; 50-mg/ml injection

Dog: 0.1-1.0 mg/dog PO q24hr Cat: 0.05-0.1 mg/cat PO q24hr

Difloxacin

Dicural

11.4-, 45.4-, and 136-mg tablets

Dog: 5-10 mg/kg/day PO Cat: Safe dose not established

Digoxin

Lanoxin, Cardoxin

0.0625-, 0.125-, 0.25-mg tablets; 0.05- and 0.15-mg/ml elixir

Dog: 20 kg use 0.22 mg/m2 PO q12hr (subtract 10% for elixir) Dog: (rapid digitalization): 0.0055- 0.011 mg/kg IV q1hr to effect Cat: 0.008-0.01 mg/kg PO q48hr (approximately ¼ of a 0.125-mg tablet/cat)

Dihydrotachysterol (vitamin D)

Hytakerol, DHT

0.125-mg tablet; 0.5-mg/ml oral liquid

0.01 mg/kg/day PO; for acute ­ treatment administer 0.02 mg/kg initially, then 0.01-0.02 mg/kg PO q24-48hr thereafter Continued

1314

Appendix  I  Table of Common Drugs: Approximate Dosages

Appendix I—cont’d Drug Name

Other Names

Formulations Available

Dosage

Diltiazem

Cardizem, Dilacor

30-, 60-, 90-, and 120-mg tablets; 50-mg/ml injection

Dog: 0.5-1.5 mg/kg PO q8hr, 0.25 mg/kg over 2 min IV (repeat if necessary) Cat: 1.75-2.4 mg/kg PO q8hr For Dilacor XR or Cardizem CD dose is 10 mg/kg PO once daily

Dimenhydrinate

Dramamine (Gravol in Canada)

50-mg tablets; 50-mg/ml injection

Dog: 4-8 mg/kg PO, IM, IV q8hr Cat: 12.5 mg/cat IV, IM, PO q8hr

Dimercaprol (BAL)

BAL in oil

Injection

4 mg/kg IM q4hr

Dinoprost tromethamine

See Prostaglandin F2α 5-mg/ml injection

Dioctyl calcium sulfosuccinate

See Docusate calcium

Dioctyl sodium sulfosuccinate

See Docusate sodium

Diphenhydramine

Benadryl

Available OTC: 2.5-mg/ml elixir; 25- and 50-mg capsules and tablets; 50-mg/ml injection

Dog: 25-50 mg/dog IV, IM, PO q8hr Cat: 2-4 mg/kg q6-8hr PO or 1 mg/kg IM, IV q6-8hr

Diphenoxylate

Lomotil

2.5 mg

Dog: 0.1-0.2 mg/kg PO q8-12hr Cat: 0.05-0.1 mg/kg PO q12hr

Diphenylhydantoin

See Phenytoin

Diphosphonate disodium etidronate

See Etidronate disodium

Dipyridamole

Persantine

25-, 50-, 75-mg tablets; 5-mg/ml injection

4-10 mg/kg PO q24hr

Dirlotapide

Slentrol

5-mg/ml oral oil-based solution

Dog: Start with 0.01 ml/kg/day PO Adjust by doubling the dose in 2 wks. Monthly adjustments to dose should be done on the basis of animal’s weight loss. Do not exceed 0.2  ml/kg/day. Cat: Do not administer to cats

Disopyramide

Norpace (Rhythmodan in Canada)

100- and 150-mg capsules (10-mg/ml injection in Canada only)

6-15 mg/kg PO q8hr

Dithiazanine iodide

Dizan

10-, 50-, 100-, and 200-mg tablets

Heartworm: 6.6-11 mg/kg PO q24hr for 7-10 days For other parasites: 22 mg/kg PO

Divalproex sodium

See Valproic acid

Dobutamine

Dobutrex

250-mg/20-ml vial for injection (12.5 mg/ml)

Dog: 5-20 mcg/kg/min IV infusion Cat: 2 mcg/kg/min IV infusion

Docusate calcium

Surfak, Doxidan

60-mg tablet (and many others)

Dog: 50-100 mg/dog PO q12-24hr Cat: 50 mg/cat PO q12-24hr

Docusate sodium

Colace, Doxan, Doss, many OTC brands

50-, and 100-mg capsules; 10-mg/ml liquid

Dog: 50-200 mg/dog PO q8-12hr Cat: 50 mg/cat PO q12-24hr

Dolasetron mesylate

Anzemet

50-, 100-mg tablets; 20- mg/ml injection

Dog, cat: Prevention of nausea and vomiting: 0.6  mg/kg IV or PO q24hr Treating vomiting and nausea: 1.0  mg/kg PO or IV once daily

Domperidone

Motilium

Not available in US

2-5 mg/animal PO

Dopamine

Intropin

40-, 80-, or 160-mg/ml

Dog, cat: 2-10 mcg/kg/min IV infusion

Doxapram

Dopram, Respiram

20-mg/ml injection

5-10 mg/kg IV Neonate: 1-5 mg SC, sublingual, or via umbilical vein

Appendix  I  Table of Common Drugs: Approximate Dosages



1315

Drug Name

Other Names

Formulations Available

Dosage

Doxorubicin

Adriamycin

2-mg/ml injection

30 mg/m2 IV q21 days or >20 kg use 30 mg/m2 and 45.8 kg, 180 mcg; or approximately 2.6-5 mcg/kg/day PO Cat: Safe dose not established

Midazolam

Versed

5-mg/ml injection

Dog: 0.1-0.25 mg/kg IV, IM (or 0.1-0.3 mg/kg/hr IV infusion) Cat: 0.05 mg/kg IV; or 0.3-0.6 mg/ kg IV (combine with 3 mg/kg ketamine)

Milbemycin oxime

Interceptor and Interceptor Flavor Tabs

23-, 11.5-, 5.75-, and 2.3-mg tablets

Dog: Microfilaricide; 0.5 mg/kg; Demodex: 2 mg/kg PO q24hr for 60-120 days Heartworm ­prevention: 0.5 mg/kg PO q30 days Cat: 2 mg/kg q30 days PO

Milk of Magnesia

See Magnesium hydroxide

Mineral oil

Generic

Oral liquid

Dog: 10-50 ml/dog PO q12hr Cat: 10-25 ml/cat PO q12hr

Minocycline

Minocin

50-, 75-, and 100-mg tablets or capsules; 10-mg/ml oral suspension

5-12.5 mg/kg PO q12hr

Misoprostol

Cytotec

0.1-mg (100 mcg), 0.2-mg (200 mcg) tablets

Dog: 2-5 mcg/kg PO q6-8hr; for atopic dermatitis 5 mcg/kg q8hr PO Cat: Dose not established

Mithramycin

See Plicamycin (Mithracin)

Mitotane (o,p’-DDD)

Lysodren

500-mg tablet

Dog: For pituitary-dependent ­hypercorticism: 50 mg/kg/day (in divided doses) PO for 5-10 days, then 50-70 mg/kg/wk PO For adrenal tumor: 50-75 mg/kg day for 10 days, then 75-100 mg/kg/wk PO

Mitoxantrone

Novantrone

2-mg/ml injection

Dog: 6 mg/m2 IV q21 days Cat: 6.5 mg/m2 IV q21 days

Appendix  I  Table of Common Drugs: Approximate Dosages



1325

Drug Name

Other Names

Formulations Available

Dosage

Morphine

Generic

1- and 15-mg/ml injection; 30- and 60-mg delayed-release tablets

Dog: 0.1-1 mg/kg IV, IM, SC (dose is escalated as needed for pain relief) q4-6hr; Dog: 0.5 mg/kg q2hr IV, IM, or CRI 0.2 mg/kg followed by 0.1 mg/kg/hr IV Epidural: 0.1 mg/kg Cat: 0.1 mg/kg q3-6hr IM, SC (or as needed)

Moxidectin

Cydectin

Injection

Dog: Heartworm prevention: 3 mcg/kg Endoparasites: 25-300 mcg/kg Demodex: 400 mcg/kg/day up to 500 mcg/kg/day for 21-22 wks

Moxifloxacin

Avelox

400-mg tablet

10 mg/kg q24hr PO

Mycochrysine

See Gold sodium thiomalate

Mycophenolate

Cell Cept

250-mg capsule

Dog: 10  mg/kg q8hr PO Cat: No dose established

Naloxone

Narcan

20- or 400-mcg/ml injection

0.01-0.04 mg/kg IV, IM, SC as needed to reverse opiate

Naltrexone

Trexan

50-mg tablet

For behavior problems: 2.2 mg/kg PO q12hr

Nandrolone decanoate

Deca-Durabolin

Nandrolone decanoate injection: 50-, 100-, and 200-mg/ml

Dog: 1-1.5 mg/kg/wk IM Cat: 1 mg/cat/wk IM

Naproxen

Naprosyn, Naxen, Aleve (naproxen sodium)

220-mg tablet (OTC); 25-mg/ml suspension liquid; 250-, 375-, and 500-mg tablets (Rx)

Dog: 5 mg initially, then 2 mg/kg q48hr Cat: Not recommended

Neomycin

Biosal

500-mg bolus; 200-mg/ml oral liquid

10-20 mg/kg PO q6-12hr

Neostigmine bromide and neostigmine methylsulfate

Prostigmin; Stiglyn

15-mg tablet (neostigmine bromide); 0.25- and 0.5-mg/ml injection (neostigmine methylsulfate)

2 mg/kg/day PO (in divided doses, to effect) Injection: Antimyasthenic: 10 mcg/kg IM, SC, as needed Antidote for nondepolarizing neuromuscular block: 40 mcg/kg IM, SC Diagnostic aid for myasthenia gravis: 40 mcg/kg IM or 20 mcg/kg IV

Nifedipine

Adalat, Procardia

10- and 20-mg capsules

Dose not established; in humans, the dose is 10 mg/human three times/day and increased in 10-mg ­increments to effect

Nitenpyram

Capstar

11.4- or 57-mg tablet

1 mg/kg PO daily as needed to kill fleas

Nitrates

See Nitroglycerin, Isosorbide dinitrate, or Nitroprusside

Nitrofurantoin

Macrodantin, Furalan, Furatoin, Furadantin, or generic

Macrodantin and generic 25-, 50-, and 100-mg capsules; Furalan, Furatoin, and generic 50- and 100-mg tablets; Furadantin 5-mg/ml oral suspension

10 mg/kg/day divided into four daily treatments, then 1 mg/kg PO at night

Nitroglycerin ointment

Nitrol, Nitro-Bid, Nitrostat

0.5-, 0.8-, 1-, 5-, and 10-mg/ml injection; 2% ointment; transdermal systems (0.2 mg/hr patch)

Dog: 4-12 mg (up to 15 mg) topically q12hr Cat: 2-4 mg topically q12hr (or ¼ inch of ointment per cat)

Nitroprusside

Nitropress

50-mg vial for injection

1-5, up to a maximum of 10 mcg/kg/min IV infusion

Nizatidine

Axid

150- and 300-mg capsules

Dog: 5 mg/kg PO q24hr

Norfloxacin

Noroxin

400-mg tablet

22 mg/kg PO q12hr

o,p’-DDD

See Mitotane (Lysodren ) Continued

1326

Appendix  I  Table of Common Drugs: Approximate Dosages

Appendix I—cont’d Drug Name

Other Names

Formulations Available

Dosage

Olsalazine

Dipentum

500-mg tablet

Dose not established (usual human dose is 500 mg or 5-10 mg/kg PO twice daily)

Omeprazole

Prilosec (formerly Losec), Gastrogard (equine paste)

20-mg capsule

Dog: 20 mg/dog PO once daily (or 0.7 mg/kg q24hr) Cat: 0.5-0.7 mg/kg q24hr PO

Ondansetron

Zofran

4- and 8-mg tablets; 2-mg/ml injection

0.5-1.0 mg/kg IV, PO 30 minutes before administration of cancer drugs

Orbifloxacin

Orbax

5.7-, 22.7-, and 68-mg tablets

2.5-7.5 mg/kg PO once daily

Ormetoprim

See Primor (ormetoprim-sulfadimethoxine)

Oxacillin

Prostaphlin and generic

250- and 500-mg capsules; 50-mg/ml oral solution

22-40 mg/kg PO q8hr

Oxazepam

Serax

15-mg tablet

Cat: Appetite stimulant: 2.5 mg/cat PO

Oxtriphylline

Choledyl-SA

400- and 600-mg tablet (oral solutions and syrup available in Canada but not US)

Dog: 47 mg/kg (equivalent to 30 mg/kg theophylline) PO q12hr

Oxybutynin chloride

Ditropan

5-mg tablet

Dog: 5 mg/dog PO q6-8hr

Oxymetholone

Anadrol

50-mg tablet

1-5 mg/kg/day PO

Oxymorphone

Numorphan

1.5- and 1-mg/ml injection

Dog, cat: Analgesia: 0.1-0.2 mg/kg IV, SC, IM (as needed), redose with 0.05-0.1 mg/kg q1-2hr ­Preanesthetic: 0.025-0.05 mg/kg IM, SC

Oxytetracycline

Terramycin

250-mg tablets; 100- and 200-mg/ml injection

7.5-10 mg/kg IV q12hr; 20 mg/kg PO q12hr

Oxytocin

Pitocin and Syntocinon (nasal solution) and generic

10- and 20-U/ml injection; 40-U/ml nasal solution

Dog: 5-20 U/dog SC, IM (repeat every 30 min for primary inertia) Cat: 2.5-3 U/cat SC, IM (repeat every 30 min)

2-PAM

See Pralidoxime chloride

Pamidronate

Aredia

30-, 60-, 90-mg vials for injection

Dog: 2  mg/kg IV, SC For treatment of cholecalciferol toxicosis: 1.3-2  mg/kg for two treatments

Pancreatic enzyme

See Pancrelipase

Pancrelipase

Viokase

16,800 U of lipase, 70,000 U of ­protease, and 70,000 U of ­ amylase per 0.7 gm; also capsules and tablets

Mix 2 tsp powder with food per 20 kg body weight or 1-3 tsp/0.45 kg of food 20 min before feeding

Pancuronium bromide

Pavulon

1- and 2-mg/ml injection

0.1 mg/kg IV or start with 0.01 mg/kg and additional 0.01-mg/kg doses every 30 min

Pantoprazole

Protonix

40-mg tablets, 0.4-mg/ml vials for injection

Dog, cat: 0.5  mg/kg q24hr IV or 0.5-1  mg/kg IV infusion over 24 hr

Paregoric

Corrective mixture

2 mg morphine per 5 ml of paregoric

0.05-0.06 mg/kg PO q12hr

Paroxetine

Paxil

10-, 20-, 30-, and 40-mg tablets

Cat: 1/8 to ¼ of a 10-mg tablet daily PO

d-Penicillamine

Cuprimine, Depen

125- and 250-mg capsules and 250-mg tablets

10-15 mg/kg PO q12hr

Penicillin G benzathine

Benza-pen and other names

150,000 U/ml, combined with 150,000 U/ml of procaine penicillin G

24,000 U/kg IM q48hr

Penicillin G potassium; penicillin G sodium

Many brands

5- to 20-million unit vials

20,000-40,000 U/kg IV, IM q6-8hr

Appendix  I  Table of Common Drugs: Approximate Dosages



1327

Drug Name

Other Names

Formulations Available

Dosage

Penicillin G procaine

Generic

300,000 U/ml suspension

20,000-40,000 U/kg IM q12-24hr

Penicillin V

Pen-Vee

250- and 500-mg tablets

10 mg/kg PO q8hr

Pentobarbital

Nembutal and generic

50 mg/ml

25-30 mg/kg IV to effect; or 2-15 mg/kg IV to effect, followed by 0.2-1.0 mg/kg/hr IV

Pentoxifylline

Trental

400-mg tablet

Dog: For use in canine dermatology and for vasculitis, 10 mg/kg PO q12hr and up to 15 mg/kg q8hr Cat: ¼ of 400-mg tab PO, q8-12hr

Pepto Bismol

See Bismuth subsalicylate

Phenobarbital

Luminal and generic

15-, 30-, 60-, and 100-mg tablets; 30-, 60-, 65-, and 130-mg/ml injection; 4-mg/ml oral elixir solution

Dog: 2-8 mg/kg PO q12hr Cat: 2-4 mg/kg PO q12hr Dog and cat: Adjust dose by monitoring plasma concentration Status epilepticus: Administer in increments of 10-20 mg/kg IV (to effect)

Phenoxybenzamine

Dibenzyline

10-mg capsule

Dog: 0.25 mg/kg PO q8-12hr or 0.5 mg/kg q24hr Cat: 2.5 mg/cat q8-12hr or 0.5 mg/cat PO q12hr (in cats, doses as high as 0.5 mg/kg IV have been used to relax urethral smooth muscle)

Phentolamine

Regitine (Rogitine in Canada)

5-mg vial for injection

0.02-0.1 mg/kg IV

Phenylbutazone

Butazolidin and generic

100-, 200-, 400-mg and 1-gm tablets; 200-mg/ml injection

Dog: 15-22 mg/kg PO, IV q8-12hr (44 mg/kg/day) (800 mg/dog maximum) Cat: 6-8 mg/kg IV, PO q12hr

Phenylephrine

Neo-Synephrine

10-mg/ml injection; 1% nasal solution

0.01 mg/kg IV q15min 0.1 mg/kg IM, SC q15min

Phenylpropanolamine

PPA, Propalin, Proin PPA

25-, 50-, and 75-mg tablets and 25-mg/ml liquid

Dog: 1 mg/kg q12hr, PO and increase to 1.5-2.0 mg/kg as needed q8hr PO

Phenytoin

Dilantin

30- and 125-mg/ml oral suspension; 30- and 100-mg capsules; 50-mg/ml injection

Antiepileptic dog: 20-35 mg/kg q8hr Antiarrhythmic: 30 mg/kg PO q8hr or 10 mg/kg IV over 5 min

Physostigmine

Antilirium

1-mg/ml injection

0.02 mg/kg IV q12hr

Phytomenadione

See Vitamin Ki

Phytonadione

See Vitamin Ki

Pimobendan

Vetmedin

2.5- and 5-mg capsules (Europe and Canada); 1.25-, 2.5-, 5-mg chewable tablets (US)

Dog: 0.05  mg/kg/day in divided ­treatments q12hr Cat: Dose not established

Piperacillin

Pipracil

2-, 3-, 4-, and 40-gm vials for injection

40 mg/kg IV or IM q6hr

Piperazine

Many

860-mg powder; 140-mg capsule, 170-, 340-, and 800-mg/ml oral solution

44-66 mg/kg PO administered once

Piroxicam

Feldene and generic

10-mg capsule

Dog: 0.3 mg/kg PO q48hr Cat: 0.3 mg/kg q24hr PO

Pitressin (ADH)

See Vasopressin, Desmopressin acetate

Plicamycin (old name is Mithracin mithramycin)

2.5-mg injection

Dog: Antineoplastic: 25-30 mcg/kg day IV (slow infusion) for 8-10 days Antihypercalcemic: 25 mcg/kg/day IV (slow infusion) over 4 hr Cat: Not recommended Continued

1328

Appendix  I  Table of Common Drugs: Approximate Dosages

Appendix I—cont’d Drug Name

Other Names

Formulations Available

Dosage

Polyethylene glycol electrolyte solution

GoLYTELY

Oral solution

25 ml/kg PO repeat in 2-4 hr PO

Polysulfated glycosami- Adequan Canine noglycan (PSGAG)

100-mg/ml injection in 5-ml vial (for horses vials are 250 mg/ml)

4.4 mg/kg IM twice weekly for up to 4 wks

Potassium bromide (KBr)

No commercial formulation

Usually prepared as oral solution Must be compounded

Dog and cat: 30-40 mg/kg PO q24hr If administered without phenobarbital, higher doses of up to 40-50 mg/kg may be needed. Adjust doses by monitoring plasma concentrations. Loading doses of 600-800 mg/kg divided over 3-4 days have been administered.

Postassium chloride (KCI)

Generic

Various concentrations for injection (usually 2 mEq/ml); oral suspension and oral solution

0.5 mEq potassium/kg/day; or ­supplement 10-40 mEq/500 ml of fluids, depending no serum potassium

Postassium citrate

Generic, Urocit-K

5-mEq tablet; some forms are in 0.5 mEq/kg/day PO combination with postassium chloride

Potassium gluconate

Kaon, Tumil-K, generic

2-mEq tablet; 500-mg tablet; Kaon elixir is 20-mg/15-ml elixir

Postassium iodide

Dog: 0.5 mEq/kg PO q12-24hr Cat: 2-8 mEq/day PO divided twice daily 30-100 mg/cat daily (in single or divided doses) for 10-14 days

Pralidoxime chloride (2-PAM)

2-PAM, Protopam Chloride

50-mg/ml injection

20 mg/kg q8-12hr (initial dose) IV slow or IM

Praziquantel

Droncit

23- and 34-mg tablets; 56.8-mg/ml injection

Dog (PO): 6.8 kg, 5 mg/kg, once (IM, SC): 5 kg, 5 mg/kg, once Cat (PO): 1.8 kg, 5 mg/kg, once (for ­Paragonimus use 25 mg/kg q8hr for 2-3 days) (IM, SC): 5 mg/kg

Prazosin

Minipress

1-, 2-, and 5-mg capsules

0.5- and 2-mg/animal (1 mg/15 kg) PO q8-12hr

Prednisolone

Delta-Cortef and many others

5- and 20-mg tablets

Dog (cat often requires two times dog dose) Antiinflammatory: 0.5-1 mg/kg IV, IM, PO q12-24hr initially, then taper to q48hr Immunosuppressive: 2.2-6.6 mg/kg/day IV, IM, PO initially, then taper to 2-4 mg/kg q48hr Replacement therapy: 0.2-0.3 mg/kg/ day PO

Prednisolone sodium succinate

Solu-Delta-Cortef

100- and 200-mg vials for injection (10 and 50 mg/ml)

Shock: 15-30 mg/kg IV (repeat in 4-6 hr) Central nervous system trauma: 15-30 mg/kg IV, taper to 1-2 mg/kg q12hr

Prednisone

Deltasone and generic; Meticorten 1-, 2.5-, 5-, 10-, 20-, 25-, and 50-mg for injection tablets; 1-mg/ml syrup (LiquidPred in 5% alcohol) and 1-mg/ml oral solution (in 5% alcohol); 10- and 40-mg/ml prednisone suspension for injection

Same as prednisolone, except that prednisone is not recommended for cats

Appendix  I  Table of Common Drugs: Approximate Dosages



1329

Drug Name

Other Names

Formulations Available

Dosage

Primidone

Mylepsin, Neurosyn (Mysoline in Canada)

50- and 250-mg tablets

8-10 mg/kg PO q8-12hr as initial dose, then is adjusted via monitoring to 10-15 mg/kg q8hr

Primor (ormetoprim + sulfadimethoxine)

Primor

Combination tablet (ormetoprim + sulfadimethoxine)

27 mg/kg on first day, followed by 13.5 mg/kg PO q24hr

Procainamide

Pronestyl, generic

250-, 375-, 500-mg tablets or capsules; 100- and 500-mg/ml injection

Dog: 10-30 mg/kg PO q6hr (to a ­maximum dose of 40 mg/kg), 8-20 mg/kg IV IM; 25-50 mcg/kg/ min IV infusion Cat: 3-8 mg/kg IM, PO q6-8hr

Prochlorperazine

Compazine

5-, 10-, and 25-mg tablets (prochlorperazine maleate); 5-mg/ml injection (prochlorperazine edisylate)

0.1-0.5 mg/kg IM, SC q6-8hr

Progesterone, repositol

See Medroxyprogesesterone acetate

Promethazine

Phenergan

6.25- and 25-mg/5-ml syrup; 12.5-,25-, 50-mg tablets; 25- and 50-mg/ml injection

0.2-0.4 mg/kg IV, IM PO q6-8hr (up to a maximum dose of 1 mg/kg)

Propantheline bromide

Pro-Banthine

7.5- and 15-mg tablet

0.25-0.5 mg/kg PO q8-12hr

Propiomazine

Tranvet

5-, 10-mg/ml injection or 20-mg tablet

1.1-4.4 mg/kg q12-24hr PO or 0.1-1.1 mg/kg IM, IV (range of dose depends on degree of sedation needed)

Propofol

Rapinovet and PropoFlo (veterinary); Diprivan (human)

1% (10 mg/ml) injection in 20-ml ampules

6.6 mg/kg IV slowly over 60 seconds; constant-rate IV infusions have been used at 5 mg/kg slowly IV, followed by 100-400 mcg/kg/min IV

Propranolol

Inderal

10-, 20-, 40-, 60-, 80-, and 90-mg tablets; 1-mg/ml injection; 4- and 8-mg/ml oral solution

Dog: 20-60 mcg/kg over 5-10 min IV; 0.2-1 mg/kg PO q8hr (titrate dose to effect) Cat: 0.4-1.2 mg/kg (2.5-5 mg/cat) PO q8hr

Propylthiouracil (PTU)

Generic, Propyl-Thyracil

50- and 100-mg tablets

11 mg/kg PO q12hr

Prostaglandin F2 alpha (dinoprost)

Lutalyse

5-mg/ml solution for injection

Pyometra: Dog: 0.1-0.2 mg/kg SC once daily for 5 days Cat: 0.1-0.25 mg/kg SC once daily for 5 days Abortion: Dog: 0.025-0.05 mg (25-50 mcg)/kg IM q12hr Cat: 0.5-1 mg/kg IM for two injections

Pseudoephedrine

Sudafed and many others (some formulations have been discontinued)

30- and 60-mg tablets; 120-mg capsule; 6-mg/ml syrup

0.2-0.4 mg/kg (or 15-60 mg/dog) PO q8-12hr

Psyllium

Metamucil and others

Available as powder

1 tsp/5-10 kg (added to each meal)

Pyrantel pamoate

Nemex, Strongid

180-mg/ml paste and 50-mg/ml suspension

Dog: 5 mg/kg PO once and repeat in 7-10 days Cat: 20 mg/kg PO once

Pyridostigmine bromide

Mestinon, Regonol

12-mg/ml oral syrup; 60-mg tablet; 5-mg/ml injection

Antimyasthenic: 0.02-0.04 mg/kg IV q2hr or 0.5-3 mg/kg PO q8-12hr Antidote (nondepolarizing muscle relaxant): 0.15-0.3 mg/kg IM, IV

Pyrimethamine

Daraprim, ReBalance (Equine)

25-mg tablet Equine formulation (ReBalance) contains 250 mg sulfadiazine and 12.5 mg pyrimethamine per ml

Dog: 1 mg/kg PO q24hr for 14-21 days (5 days for Neosporum caninum) Cat: 0.5-1 mg/kg PO q24hr for 14-28 days Continued

1330

Appendix  I  Table of Common Drugs: Approximate Dosages

Appendix I—cont’d Drug Name

Other Names

Formulations Available

Dosage

Quinidine gluconate

Quiniglute, Duraquin

324-mg tablets; 80-mg/ml injection

Dog: 6-20 mg/kg IM q6hr; 6-20 mg/kg PO q6-8hr (of base)

Quinidine sulfate

Cin-Quin, Quinora

100-, 200-, and 300-mg tablets; 200- and 300-mg capsules; 20-mg/ml injection

Dog: 6-20 mg/kg PO q6-8hr (of base); 5-10 mg/kg IV

Quinidine polygalacturonate

Cardioquin

275-mg tablet

Dog: 6-20 mg/kg PO q6hr (of base) (275 mg quinidine polygalacturonate = 167 mg quinidine base)

Racemethionine (dl-methionine)

Uroeze, MethioForm, and generic. Human forms include Pedameth, Uracid, and generic

500-mg tablets and powders added to animal’s food; 75-mg/5 ml pediatric oral solution; 200-mg capsule

Dog: 150-300 mg/kg/day PO Cat: 1-1.5 gm/cat PO (added to food each day)

Ranitidine

Zantac

75-, 150-, and 300-mg tablets; 150- and 300-mg capsules; 25-mg/ml injection

Dog: 2 mg/kg IV, PO q8hr Cat: 2.5 mg/kg IV q12hr, 3.5 mg/kg PO q12hr

Retinoids

See Isotretinoin (Accutane), Retinol (Aquasol-A), or Etretinate (Tegison)

Retinol

See Vitamin A (Aquasol-A)

Riboflavin (vitamin B2)

See Vitamin B2

Rifampin

Rifadin

150- and 300-mg capsules

5-15 mg/kg PO q24hr

Ringer’s solution

Generic

250-, 500-, and 1000-ml bags for infusion

55-65 ml/kg/day IV, SC, or IP; 50 ml/ kg/hr IV for severe dehydration

Ronidazole

No formulation available; must be compounded

There are no commercial formulations. However, compounding pharmacies have prepared formulations for cats.

Dog: Dose not established Cat: 30-60  mg/kg/day PO for 2 wks

Salicylate

See Aspirin, acetylsalicylic acid

Selegiline (deprenyl)

Anipryl (also known as deprenyl, and l-deprenyl); human dose form is Eldepryl

2-, 5-, 10-, 15-, and 30-mg tablets

Dog: Begin with 1 mg/kg PO q24hr; If there is no response within 2 months, increase dose to maximum of 2 mg/kg PO q24hr Cat: 0.25-0.5 mg/kg q12-24hr PO

Senna

Senokot

Granules in concentrate, or syrup

Dog: Syrup; 5-10 ml/dog q24hr; Granules: 1/2 to 1 tsp/dog q24hr PO with food Cat: Syrup: 5 ml/cat q24hr; granules: ½ teaspoon/cat q24hr (with food)

Septra (sulfamethoxazole + trimethoprim)

See Trimethoprim/sulfonamides

Sildenafil

Viagra

25-, 50-, 100-mg tablets

Dog: 0.5-1  mg/kg q12hr PO; higher dose of 2-3  mg/kg q8hr may be needed in some cases

Silymarin

Silybin, Marin, “milk thistle”

Silymarin tablets are widely available OTC. Commercial veterinary formulations (Marin) also contain zinc and vitamin E in a phosphatidylcholine complex in tablets for dogs and cats.

30  mg/kg/day PO

Sodium bicarbonate (NaHCO3)

Generic, Baking Soda, Soda Mint

325-, 520-, and 650-mg tablets; injection of various strengths (4.2% to 8.4%), and 1 mEq/ml

Acidosis: 0.5-1 mEq/kg IV Renal failure: 10 mg/kg PO q8-12hr Alkalization of urine: 50 mg/kg PO q8-12hr (1 tsp is approximately 2 gm)

Appendix  I  Table of Common Drugs: Approximate Dosages



1331

Drug Name

Other Names

Formulations Available

Dosage

Sodium bromide

No commercial form

Must be compounded

Same as potassium bromide, except dose is 15% lower (30 mg/kg potassium bromide is equivalent to 25 mg/kg sodium bromide)

Sodium chloride 0.9%

Generic

500- and 1,000-ml infusion

15-30 ml/kg/hr IV

Sodium chloride 7.5%

Generic

Infusion

2-8 ml/kg IV

Sodium thiomalate

See Gold sodium thiomalate

Somatrem, Somatropin See Growth hormone Sotalol

Betapace

80-, 160-, 240-mg tablets

Dog: 1-2 mg/kg PO q12hr (one can start with 40 mg/dog q12hr, then increase to 80 mg if no response) Cat: 1-2 mg/kg PO q12hr

Spironolactone

Aldactone

25-, 50-, and 100-mg tablets

2-4 mg/kg/day (or 1-2 mg/kg PO q12hr)

Stanozolol

Winstrol-V

50-mg/ml injection; 2-mg tablet

Dog: 2 mg/dog (or range of 1-4 mg/ dog) PO q12hr; 25-50 mg/dog/wk IM Cat: 1 mg/cat PO q12hr; 25 mg/cat/ wk IM

Succimer

Chemet

100-mg capsule

Dog: 10 mg/kg PO q8hr for 5 days, then 10 mg/kg PO q12hr for 2 more wks Cat: 10 mg/kg q8hr for 2 wks

Sucralfate

Carafate (Sulcrate in Canada)

1-gm tablet; 200-mg/ml oral suspension

Dog: 0.5-1 gm/dog PO q8-12hr Cat: 0.25 gm/cat PO q8-12hr

Sufentanil citrate

Sufenta

50-mcg/ml injection

2 mcg/kg IV, up to a maximum dose of 5 mcg/kg

Sulfadiazine

Generic, combined with trimethoprim in Tribrissen

500-mg tablet; trimethoprimsulfadiazine 30-, 120-, 240-, 480-, and 960-mg tablets

100 mg/kg IV, PO (loading dose), ­followed by 50 mg/kg IV, PO q12hr (see also Trimethoprim)

Sulfadimethoxine

Albon, Bactrovet, and generic

125-, 250-, and 500-mg tablets; 400-mg/ml injection; 50-mg/ml suspension

55 mg/kg PO (loading dose), followed by 27.5 mg/kg PO q12hr (see also Primor)

Sulfamethoxazole

Gantanol

50-mg tablet

100 mg/kg PO (loading dose), ­followed by 50 mg/kg PO q12hr (see also Bactrim, Septra)

Sulfasalazine (sulfapyridine + mesalamine)

Azulfidine (Salazopyrin in Canada)

500-mg tablet

Dog: 10-30 mg/kg PO q8-12hr (see also Mesalamine, Olsalazine) Cat: 20 mg/kg q12hr PO

Sulfisoxazole

Gantrisin

500-mg tablet; 500-mg/5 ml syrup

50 mg/kg PO q8hr (urinary tract infections)

Tamoxifen

Nolvadex

10- and 20-mg tablets (tamoxifen citrate)

Veterinary dose not established; 10 mg PO q12hr is human dose

Taurine

Generic

Available in powder

Dog: 500 mg PO q12hr Cat: 250 mg/cat PO q12hr

Telezol

See Tiletamine-Zolazepam

Tepoxalin

Zubrin

50-, 100-, 200-mg tablets

Dog: 10-20  mg/kg PO initially, followed by 10  mg/kg q24hr PO thereafter Cat: Safe dose not established

Terbinafine

Lamisil

125-, 250-mg tablets

Dog: Malassezia dermatitis: 30  mg/kg/ day PO Cat: Dermatophytosis: 30-40  mg/kg PO q24hr

Terbutaline

Brethine, Bricanyl

2.5- and 5-mg tablets; 1-mg/ml injection (equivalent to 0.82 mg/ml)

Dog: 1.25-5 mg/dog PO q8hr Cat: 0.1-0.2 mg/kg PO q12hr (or 0.625 mg/cat, ¼ of 2.5-mg tablet) For acute treatment in cats: 5-10 mcg/ kg q4hr SC or IM Continued

1332

Appendix  I  Table of Common Drugs: Approximate Dosages

Appendix I—cont’d Drug Name

Other Names

Testosterone cypionate ester

Andro-Cyp, Andronate, 100- and 200-mg/ml injection Depo-Testosterone and other forms

Formulations Available

1-2 mg/kg IM q2-4wk (see also Methyltestosterone)

Dosage

Testosterone propionate ester

Testex (Malogen in Canada)

100-mg/ml injection

0.5-1 mg/kg 2-3 times/wk IM

Tetracycline

Panmycin

250- and 500-mg capsules; 100-mg/ml suspension

15-20 mg/kg PO q8hr; or 4.4-11 mg/kg IV, IM q8hr

Thenium closylate

Canopar

500-mg tablet

Dog: >4.5 kg: 500 mg PO once, repeat in 2-3 wks 2.5-4.5 kg: 250 mg q12hr for 1 day, repeat in 2-3 wks

Theophylline

Many brands and generic

100-, 125-, 200-, 250-, and 300-mg tablets; 27-mg/5 ml oral solution or elixir; injection in 5% dextrose

Dog: 9 mg/kg PO q6-8hr Cat: 4 mg/kg PO q8-12hr

Theopylline extended-release

Inwood labs extended release

100-, 200-, 300-, and 400-mg tablets or 125-, 200-, 300-mg capsules

Dog: 10 mg/kg q12hr PO of extended-release tablet or capsule Cat: 20 mg/kg q24-48hr PO extendedrelease tablet or 25 mg/kg q24-48hr PO extended-release capsule

Thiamine (vitamin B1)

Bewon and others

250-mcg/5 ml elixir; tablets of various size from 5 mg to 500 mg; 100- and 500-mg/ml injection

Dog: 10-100 mg/dog/day PO or 12.550 mg/dog IM or SC/day Cat: 5-30 mg/cat/day PO (up to a maximum dose of 50 mg/cat/day) or 12.5-25 mg/cat IM or SC/day

Thiamylal sodium

No longer available; substitute Thiopental

Thioguanine (6-TG)

Generic

Thiomalate sodium

See Gold sodium thiomalate

Thiopental sodium

40-mg tablet

40 mg/m2 PO q24hr Cat: 25 mg/m2 PO q24hr for 1-5 days, then repeat every 30 days

Pentothal

Various size vials from 250 mg to 10 gm (mix to desired concentration)

Dog: 10-25 mg/kg IV (to effect) Cat: 5-10 mg/kg IV (to effect)

Thiotepa

Generic

15-mg injection (usually in solution of 10 mg/ml)

0.2-0.5 mg/m2 weekly, or daily for 5-10 days IM, intracavitary, or intratumor

Thyroid hormone

See Levothyroxine sodium (T4), or Liothyronine

Thyrotropin, thyroid-stimulating hormone (TSH)

Thytropar, thyrogen

10-U vial; old forms difficult to obtain; Dog: Collect baseline sample, followed thyrogen is 1000 mcg/vial by 0.1 U/kg IV (maximum dose is 5 U); collect post-TSH sample at 6 hr Cat: Collect baseline sample, followed by 2.5 U/cat IM and collect a post-TSH sample at 8-12 hr

Ticarcillin

Ticar, Ticillin

Vials containing 1, 3, 6, 20, and 30 gm

33-50 mg/kg IV, IM q4-6hr

Ticarcillin + clavulanate

Timentin

3-gm/vial for injection

Dose according to rate for ticarcillin

Tiletamine + zolazepam Telazol, Zoletil

50 mg of each component per milliliter

Dog: 6.6-10 mg/kg IM (short term) or 10-13 mg/kg IM (longer procedure) Cat: 10-12 mg/kg IM (minor procedure) or 14-16 mg/kg IM (for surgery)

Tobramycin

Nebcin

40-mg/ml injection

Dog: 9-14 mg/kg IM, IV, SC q24hr Cat: 5-8 mg/kg IM, SC, IV q24hr

Tocainide

Tonocard

400- and 600-mg tablets

Dog: 15-20 mg/kg PO q8hr Cat: No dose established

Toluene

Vermiplex

267 mg/kg PO (of toluene), repeat in 2-4 wk

Appendix  I  Table of Common Drugs: Approximate Dosages



Drug Name

Other Names

1333

Formulations Available

Dosage

Tramadol hydrochloride Ultram and generic

Tramadol immediate-release tablets are available in 50-mg tablets

Dog: 5  mg/kg PO q6-8hr Cat: Safe dose not established

Trandolapril

Mavik

1-, 2-, and 4-mg tablets

Not established for dogs; human dose is 1 mg/person/day to start, then increase to 2-4 mg/day

Triamcinolone

Vetalog, Trimtabs, Aristocort, generic

Veterinary (Vetalog) 0.5- and 1.5-mg tablets. Human form: 1-, 2-, 4-, 8-, and 16-mg tablets; 10-mg/ml injection

Antiinflammatory: 0.5-1 mg/kg PO q12-24hr, then taper dose to 0.5-1 PO mg/kg q48hr (however, ­manufacturer recommends doses of 0.11 to 0.22 mg/kg/day)

Triamcinolone acetonide

Vetalog

2- or 6-mg/ml suspension injection

0.1-0.2 mg/kg IM, SC, repeat in 7-10 days Intralesional: 1.2-1.8 mg, or 1 mg for every cm diameter of tumor q2wk

Triamterene

Dyrenium

50- and 100-mg capsules

1-2 mg/kg PO q12hr

Tribrissen

See Trimethoprim-sulfadimethoxine combination

Trientine hydrochloride Syprine

250-mg capsule

10-15 mg/kg PO q12hr

Trifluoperazine

Stelazine

10-mg/ml oral solution; 1-, 2-, 5-, 0.03 mg/kg IM q12hr and 10-mg tablets; 2-mg/ml injection

Triflupromazine

Vesprin

10- and 20-mg/ml injection

0.1-0.3 mg/kg IM, PO q8-12hr

Tri-iodothyronine

See Liothyronine

Trilostane

Vetoryl

10-, 30-, 60-, and 120-mg capsules; no formulations approved in US; must be imported

Dog: 3.9-9.2  mg/kg/day PO (most ­common dose is 6.1 mg/kg/day); adjust dose based on cortisol measurements

Trimeprazine tartrate

Temaril (Panectyl in Canada)

2.5-mg/5 ml syrup; 2.5-mg tablet

0.5 mg/kg PO q12hr

Trimethobenzamide

Tigan and others

100-mg/ml injection; 100- and 250-mg capsules

Dog: 3 mg/kg IM, PO q8hr Cat: Not recommended

Trimethoprim + sulfonamides (sulfadiazine or sulfamethoxazole)

Tribrissen and others

30-, 120-, 240-, 480-, and 960-mg tablets with trimethoprim to sulfa ratio 1:5

15 mg/kg PO q12hr, or 30 mg/kg PO q12-24hr For Toxoplasma: 30 mg/kg PO q12hr

Tripelennamine

Pelamine, PBZ

25- and 50-mg tablets; 20-mg/ml injection

1 mg/kg PO q12hr

TSH (thyroid-stimulating See Thyrotropin hormone) Tylosin

Tylocine, Tylan, Tylosin tartrate

Available as soluble powder 2.2 gm tylosin per tsp (tablets for dogs in Canada)

Dog, cat: 7-15 mg/kg PO q12-24hr Dog: For colitis: 10-20 mg/kg q8hr with food initially, then increase interval to q12-24hr

Urofollitropin (FSH)

Metrodin

75 U/vial for injection

75 U/day IM for 7 days

Ursodiol (ursodeoxycholate)

Actigall

300-mg capsule, 250-mg tablets

10-15 mg/kg PO q24hr

Valproic acid, divalproex

Depakene (valproic acid); Depakote (divalproex)

125-, 250-, and 500-mg tablets (Depakote); 250-mg capsule; 50-mg/ml syrup (Depakene)

Dog: 60-200 mg/kg PO q8hr; or 25-105 mg/kg/day PO when ­administered with phenobarbital

Vancomycin

Vancocin, Vancoled

Vials for injection (0.5 to 10 gm)

Dog: 15 mg/kg q6-8hr IV infusion Cat: 12-15 mg/kg q8hr IV infusion

Vasopressin (ADH)

Pitressin

20 U/ml (aqueous)

10 U IV, IM

Verapamil

Calan, Isoptin

40-, 80-, and 120-mg tablet; 2.5-mg/ml injection

Dog: 0.05 mg/kg IV q10-30 min (maximum cumulative dose is 0.15 mg/kg)

Vinblastine

Velban

1-mg/ml injection

2 mg/m2 IV (slow infusion) once/wk Continued

1334

Appendix  I  Table of Common Drugs: Approximate Dosages

Appendix I—cont’d Drug Name

Other Names

Formulations Available

Dosage

Vincristine

Oncovin, Vincasar, generic

1-mg/ml injection

Antitumor: 0.5-0.7 mg/m2 IV (or 0.025-0.05 mg/kg) once/wk For thrombocytopenia: 0.02 mg/kg IV once/wk

Viokase

See Pancrelipase

Vitamin A (retinoids)

Aquasol A

Vitamin B1

See Thiamine

Vitamin B2 (riboflavin)

Riboflavin

Various-size tablets in increments from 10 to 250 mg

Dog: 10-20 mg/day PO Cat: 5-10 mg/day PO

Vitamin B12 (cyanocobalamin)

Cyanocobalamin

Various-size tablets in increments from 25 to 100 mcg and injections

Dog: 100-200 mcg/day PO Cat: 50-100 mcg/day PO

Vitamin C (ascorbic acid)

See Ascorbic acid

Tablets of various sizes and injection

100-500 mg/day

Vitamin D

See Dihdyrotachysterol or Ergocalciferol

Vitamin E (alpha-tocopherol)

Aquasol E, and generic

Wide variety of capsules, tablets, oral solution available (e.g., 1000 units per capsule)

100-400 U PO q12hr (or 400-600 U PO q12hr for immune-mediated skin disease)

Vitamin K1 (phytonadione, phytomenadione)

AquaMEPHYTON (injection), Mephyton (tablets); Veta-K1 (capsules)

2- or 10-mg/ml injection; 5-mg tablet (Mephyton) 25-mg capsule (Veta-K1)

Short-acting rodenticides: 1 mg/kg/day IM, SC, PO for 10-14 days Long-acting rodenticides: 2.5-5 mg/kg/day and up to 6 wks IM, SC, PO for 3-4 wk Birds: 2.5-5 mg/kg q24hr

Warfarin

Coumadin, generic

1-, 2-, 2.5-, 4-, 5-, 7.5-, and 10-mg tablets

Dog: 0.1-0.2 mg/kg PO q24hr Cat: Thromboembolism: Start with 0.5 mg/cat/day and adjust dose based on clotting time assessment

Xylazine

Rompun and generic

20- and 100-mg/ml injection

Dog: 1.1 mg/kg IV, 2.2 mg/kg IM Cat: 1.1 mg/kg IM (emetic dose is 0.4-0.5 mg/kg IV)

Yohimbine

Yobine

2-mg/ml injection

0.11 mg/kg IV or 0.25-0.5 mg/kg SC, IM

Zidovudine (AZT)

Retrovir

10-mg/ml syrup; 10-mg/ml Injection

Cat: 15 mg/kg PO q12hr to 20 mg/kg q8hr (doses as high as 30 mg/kg/day also have been used)

Zolazepam

See Tiletamine-zolazepam combination

Zonisamide

Zonegram

Oral solution: 5000 U (1,500 RE) 625-800 U/kg PO q24hr per 0.1 ml 10,000-, 25,000-, and 50,000-U tablets

100-mg capsule

Dog: 3  mg/kg q8hr PO; it has also been administered to dogs at 10  mg/ kg q12hr PO Cat: Dose not established

note: Doses listed are for dogs and cats, unless otherwise listed. Many of the doses listed are extra-label or are human drugs used in an off-label or extra-label manner. Doses listed are based on best available evidence at the time of table preparation; however, the author cannot ensure efficacy of drugs used according to recommendations in this table. Adverse effects may be possible from drugs listed in this table of which author was not aware at the time of table preparation. Veterinarians using these tables are encouraged to check current literature, product label, and the manufacturer’s disclosure for information regarding efficacy and any known adverse effects or contraindications not indentified at the time of preparation of these tables. IM, Intramuscular; IV, intravenous; OTC, over-the-counter (without prescription); PO, per os (oral); Rx, prescription only; SC, subcutaneous; U, units.

Appendix 

II

Treatment of Parasites Cliff Monahan, Columbus, Ohio

Helminths Drug(s)

Species

Target Parasites

Route*

Veterinary Formulations

Emodepside/Praziquantel

Feline only

Roundworms, hookworms, Dipylidium caninum, Echinococcus multilocularis, Taenia taeniaeformis

Topical

Profender

Epsiprantel

Canine and feline

Dipylidium caninum, Taenia spp.

Oral

Cestex

Febantel/Praziquantel/Pyrantel Pamoate

Canine only

Roundworms, hookworms, Trichuris vulpis, Dipylidium caninum, Echinococcus granulosus, Taenia pisiformis

Oral

Drontal Plus

Fenbendazole

Canine

Roundworms, hookworms, Trichuris vulpis, Giardia intestinalis, Taenia pisiformis

Oral

Panacur

Imidacloprid/Moxidectin

Canine and feline

Roundworms, hookworms, Trichuris vulpis in dogs; Dirofilaria immitis prevention

Topical

Advantage Multi

Ivermectin

Canine and feline

Roundworms, hookworms, in cats, Dirofilaria immitis prevention in dogs and cats

Oral

Heartgard

Ivermectin/Praziquantel/ Pyrantel Pamoate

Canine only

Roundworms, hookworms, Dipylidium caninum, Echinococcus granulosus, Taenia pisiformis, Dirofilaria immitis prevention

Oral

Iverhart Max

Ivermectin/Pyrantel Pamoate

Canine only

Roundworms, hookworms, Dirofilaria immitis prevention

Oral

Heartgard Plus, Iverhart Plus, TriHeart Plus

Milbemycin Oxime

Canine and feline

Roundworms, Ancylostoma spp., Trichuris vulpis in dogs; Dirofilaria immitis prevention

Oral

Interceptor

Praziquantel

Canine and feline

Dipylidium caninum, Echinococcus spp., Taenia spp.

Oral injectable

Droncit

Praziquantel/Pyrantel Pamoate

Feline only

Roundworms, hookworms, Dipylidium caninum, Echinococcus multilocularis, Taenia taeniaeformis

Oral

Drontal

Pyrantel Pamoate

Canine and feline

Roundworms and hookworms in dogs and cats

Oral

Nemex

Selamectin

Canine and feline

Roundworms and hookworms in cats; Dirofilaria immitis prevention in dogs and cats

Topical

Revolution

1335

1336

Appendix  II  Treatment of Parasites

Protozoa Drug(s)

Species

Target Parasite(s)

Route(s) and Frequency of Administration

Fipronil

Canine and feline

Fleas, lice, mites, ticks

Topical, monthly

Imidacloprid

Canine and feline

Fleas, lice

Topical, monthly

Advantage

Imidacloprid/Permethrin

Canine only

Fleas, lice, mites, ticks

Topical, monthly

Advantix

Metaflumizone

Feline only

Fleas, lice

Topical, monthly

ProMeris for Cats

Metaflumizone/Amitraz

Canine only

Fleas, lice, mites, ticks

Topical, monthly

ProMeris for Dogs

Veterinary Formulations Frontline, Frontline Plus

Nitenpyram

Canine and feline

Fleas

Oral, daily

Capstar

Spinosad

Canine only

Fleas

Oral, monthly

Comfortis

Route of Administration and Dosages

Ectoparasites Veterinary Formulations

Drug(s)

Species

Target Parasite(s)

Amprolium

Canine

Isospora spp.

Oral, 100 mg/kg SID, 7-10 days

Corid

Clindamycin

Canine and feline

Toxoplasma gondii (systemic infections)

Oral, 10-15 mg/kg BID, 14-28 days as needed

Antirobe

Doxycycline

Canine and feline

Toxoplasma gondii (systemic infections)

Oral 5-10 mg/kg BID, 28 days

Vibramycin

Fenbendazole

Canine and feline

Giardia intestinalis

Oral, 50 mg/kg SID, 3 days

Panacur

Imidocarb diproprionate

Canine and reline

Babesia spp., Cytauxzoon felis

IM or SC, 6.6 mg/kg; repeat in 14 days

Imizol

Metronidazole

Canine and feline

Giardia intestinalis

Oral, 25 mg/kg SID, 5 days

Flagyl

Nitazoxanide

Canine and feline

Giardia intestinalis, Cryptosporidium spp.

Oral, 100 mg/kg BID, 3 days

Alinia (Human) Navigator (Horses)

Ponazuril

Canine and feline

Isospora spp., Toxoplasma gondii

Oral, 15 mg/kg SID, 3 days; 30 mg/kg SID, 1 day

Marquis (Horses)

Sulfadiazine and Trimethoprim

Canine and feline

Isospora spp., Toxoplasma gondii (intestinal infections)

Oral, 30 mg/kg BID, 14 days as needed

Tribrissen

Sulfadimethoxine

Canine and reline

Isospora spp., Toxoplasma gondii (intestinal infections)

Oral, 50 mg/kg day 1, then 25 mg/kg SID for 14-21 days as needed

Albon

*Follow manufacturer’s recommendations for indicated use; see Appendix I, Table of Commonly Used Drugs, for extralabel use.

Appendix 

III

AAFCO Dog and Cat Food   Nutrient Profiles David A. Dzanis, Santa Clarita, California

T

he Association of American Feed Control Officials (AAFCO) is a non-governmental body, but it is composed solely of representatives from agencies within individual states and territories, federal agencies such as the U.S. Food and Drug Administration (FDA), and foreign governments such as Canada. A primary function of AAFCO is the publication of a model feed bill, animal feed regulations, and ingredient definitions, all of which a state may  adopt as a part of its own feed laws and regulations.  A pet food that bears a “complete and balanced” label claim that does not, in fact, offer adequate nutrition is both misbranded and unsafe. To address this concern, included in the model pet food regulations are means of substantiating nutritional adequacy for complete and balanced dog and cat foods. One method of substantiating nutritional adequacy requires that the product be formulated so that essential nutrient levels meet a prescribed profile. Historically, AAFCO relied on the publications of the National Research Council (NRC) as its authority with respect to the levels of nutrients that constituted a complete and balanced dog or cat food. However, to address several technical concerns regarding the applicability of the NRC recommendations to the practical formulation of pet foods, they were replaced by the AAFCO Dog and Cat Food Nutrient Profiles (Tables 1 and 2) in the early 1990s. The profiles are the product of the AAFCO Canine Nutrition Expert (CNE) and Feline Nutritional Expert (FNE) Subcommittees, which met in 1990 and 1991, respectively. Nationally recognized experts from both academia and industry were convened to establish practical profiles based on commonly used ingredients. In addition to this author (at that time representing the FDA), members of the CNE included Dr. Jim Corbin, University of Illinois; Dr. Gail CzarneckiMaulden, Westreco, Inc.; Dr. Diane Hirakawa, The Iams Company; Dr. Francis Kallfelz, Cornell University; Dr. Mark Morris, Mark Morris Associates; and Dr. Ben Sheffy, Cornell University. Added to the original members of the CNE were two new members on the FNE to bring additional expertise in the field of cat nutrition; Dr. Quinton Rogers, University of California-Davis; and Dr. Angele Thompson, Kal Kan Foods. Mr. Wenell Kerr of Westreco, Inc., also participated to provide statistical support to both subcommittees. The CNE and FNE met once again in 1995 to review and update both the dog and the cat food profiles. At the time of this writing, 

a new AAFCO expert panel has been convened to review recent data and recommend revision of the profiles where appropriate. Nutrient levels in the AAFCO Dog and Cat Food Nutrient Profiles are based on the CNE and the FNE members’ knowledge of published and unpublished research, as well as their personal expertise and experiences in practical formulation. Much of the scientific data on nutrient requirements are based on studies using purified diets and the presumption of 100% bioavailability. However, since commercial products are composed of nonpurified, complex ingredients, allowances to account for the effects of ingredients, ingredient interactions, and processing on bioavailability were also considered in establishing nutrient levels. Comments on the bioavailability or the effect of processing and ingredient interaction on some nutrients are also added in the footnotes to tables. In addition to minimum nutrient levels, the AAFCO Dog and Cat Food Nutrient Profiles also set maximum levels of intake of some nutrients. This was done out of concern that the risk of nutrient excess, rather than deficiency, was a concern with some pet foods. Thus maximum limits on the amounts of calcium, phosphorus, magnesium, fat-soluble vitamins, and most trace minerals in dog foods are established. Whereas the list of maximum levels for cat foods is not as extensive as that for dog foods, it should not be inferred that cats are more tolerant of nutrient excesses than dogs. Rather it reflects the paucity of information on the toxic effects of nutrients in cats. Establishing maximum levels arbitrarily might prove worse than no maximum at all. Setting a maximum level implies safety below that level, which the subcommittees could not reasonably ensure. Replacing the previous “meets or exceeds the NRC recommendations” verbiage, the required label wording for reference to the nutrient profiles is that the product is “… formulated to meet the nutrient levels established by the AAFCO Dog (or Cat) Food Nutrient Profiles for …” a given life stage. For both dog and cat foods, there are two separate AAFCO profiles: one for growth and reproduction (gestation and lactation), and one for adult maintenance. This allows foods formulated for adult dogs or cats to contain lower amounts of some nutrients, eliminating unnecessary excesses. Products that meet only the adult maintenance profile should include “maintenance” as its given life stage. Since products suitable for the more stringent nutrient requirements of growth and ­ reproduction

1337

1338

Appendix  III  AAFCO Dog and Cat Food Nutrient Profiles

Table 1 AAFCO Dog Food Nutrient Profiles* Growth and Reproduction Minimum

Adult Maintenance Minimum

Nutrient

Units DM Basis

Crude protein Arginine Histidine Isoleucine Leucine Lysine Methionine-cystine Phenylalanine-tyrosine Threonine Tryptophan Valine Crude fat† Linoleic acid Minerals Calcium Phosphorus Ca:P ratio Potassium Sodium Chloride Magnesium Iron‡ Copper§ Manganese Zinc Iodine Selenium Vitamins and other Vitamin A Vitamin D Vitamin E Thiamine|| Riboflavin Pantothenic acid Niacin Pyridoxine Folic acid Vitamin B12 Choline

% % % % % % % % % % % % %

22.0 0.62 0.22 0.45 0.72 0.77 0.53 0.89 0.58 0.20 0.48 8.0 1.0

18.0 0.51 0.18 0.37 0.59 0.63 0.43 0.73 0.48 0.16 0.39 5.0 1.0

% % % % % % mg/kg mg/kg mg/kg mg/kg mg/kg mg/kg

1.0 0.8 1:1 0.6 0.3 0.45 0.04 80 7.3 5.0 120 1.5 0.11

0.6 0.5 1:1 0.6 0.06 0.09 0.04 80 7.3 5.0 120 1.5 0.11

IU/kg IU/kg IU/kg mg/kg mg/kg mg/kg mg/kg mg/kg mg/kg mg/kg mg/kg

5,000 500 50 1.0 2.2 10 11.4 1.0 0.18 0.022 1,200

5,000 500 50 1.0 2.2 10 11.4 1.0 0.18 0.022 1,200

Maximum

2.5 1.6 2:1

0.3 3,000 250 1,000 50 2 250,000 5,000 1,000

*Presumes an energy density of 3.5 kcal ME/g DM, based on the “modified Atwater” values of 3.5, 8.5, and 3.5 kcal/g for protein, fat, and carbohydrate (nitrogen-free extract, NFE), respectively. Rations greater than 4.0 kcal/g should be corrected for energy density; rations less than 3.5 kcal/g should not be ­corrected for energy. Rations of low-energy density should not be considered adequate for growth or reproductive needs based on comparison to the profiles alone. † Although a true requirement for fat per se has not been established, the minimum level was based on recognition of fat as a source of essential fatty acids, as a carrier of fat-soluble vitamins, and on the amount needed to enhance palatability and to supply an adequate caloric density. ‡ Because of very poor bioavailability, iron from carbonate or oxide sources that are added to the diet should not be considered in determining the minimum nutrient level. § Because of very poor bioavailability, copper from oxide sources that are added to the diet should not be considered in determining the minimum nutrient level. || Because processing may destroy up to 90% of the thiamine in the diet, allowances in formulation should be made to ensure that the minimum nutrient level is met after processing.

are also presumed to be adequate for adult maintenance, products meeting the growth and reproduction profile can list their intended use for either maintenance, growth, gestation and lactation, or “all life stages.” Nutrient levels in the tables are expressed on a dry matter (DM) basis. To accurately compare levels for a

pet food as given in the guaranteed analysis portion of a label or elsewhere on an “as fed” basis, the values must first be corrected for moisture content. For most dry pet foods (10% moisture), “as fed” values should be multiplied by 1.1. For 75% moisture canned product, values should be multiplied by 4.0. The profiles are also set at

APPENDIX  III  AAFCO Dog and Cat Food Nutrient Profiles



1339

Table 2 AAFCO Cat Food Nutrient Profiles* Growth and Reproduction Minimum

Adult Maintenance Minimum

Nutrient

Units DM Basis

Crude protein Arginine Histidine Isoleucine Leucine Lysine Methionine-cystine Methionine Phenylalanine-tyrosine Phenylalanine Threonine Tryptophan Valine Crude fat† Linoleic acid Arachidonic acid Minerals Calcium Phosphorus Potassium Sodium Chloride Magnesium‡ Iron§ Copper (extruded)|| Copper (canned)|| Manganese Zinc Iodine Selenium Vitamins and others Vitamin A Vitamin D Vitamin E¶ Vitamin K# Thiamine** Riboflavin Pantothenic acid Niacin Pyridoxine Folic acid Biotin†† Vitamin B12 Choline ‡‡ Taurine (extruded) Taurine (canned)

% % % % % % % % % % % % % % % %

30.0 1.25 0.31 0.52 1.25 1.20 1.10 0.62 0.88 0.42 0.73 0.25 0.62 9.0 0.5 0.02

26.0 1.04 0.31 0.52 1.25 0.83 1.10 0.62 0.88 0.42 0.73 0.16 0.62 9.0 0.5 0.02

% % % % % % mg/kg mg/kg mg/kg mg/kg mg/kg mg/kg mg/kg

1.0 0.8 0.6 0.2 0.3 0.08 80 15 5 7.5 75 0.35 0.1

0.6 0.5 0.6 0.2 0.3 0.04 80 5 5 7.5 75 0.35 0.1

IU/kg IU/kg IU/kg mg/kg mg/kg mg/kg mg/kg mg/kg mg/kg mg/kg mg/kg mg/kg mg/kg % %

9,000 750 30 0.1 5.0 4.0 5.0 60 4.0 0.8 0.07 0.02 2,400 0.10 0.20

5,000 500 30 0.1 5.0 4.0 5.0 60 4.0 0.8 0.07 0.02 2,400 0.10 0.20

Maximum

1.5

2,000

750,000 10,000

Presumes an energy density of 4.0 kcal ME/g DM, based on the “modified Atwater” values of 3.5, 8.5, and 3.5 kcal/g for protein, fat, and carbohydrate (nitrogen-free extract, NFE), respectively. Rations greater than 4.5 kcal/g should be corrected for energy density; rations less than 4.0 kcal/g should not be ­corrected for energy. Rations of low-energy density should not be considered adequate for growth or reproductive needs based on comparison to the profiles alone. † Although a true requirement for fat per se has not be established, the minimum level was based on recognition of fat as a source of essential fatty acids, as a carrier of fat-soluble vitamins, to enhance palatability, and to supply an adequate caloric density. ‡ If the mean urine pH of cats fed ad libitum is not below 6.4, the risk of struvite urolithiasis increases as the magnesium content of the diet increases. § Because of very poor bioavailability, iron from carbonate or oxide sources that are added to the diet should not be considered in determining the minimum nutrient level. || Because of very poor bioavailability, copper from oxide sources that are added to the diet should not be considered in determining the minimum nutrient level. ¶ Add 10 IU of vitamin E above minimum level per gram of fish oil per kilogram of diet. # Vitamin K does not need to be added unless diet contains more than 25% fish on a dry matter basis. ** Because processing may destroy up to 90% of the thiamine in the diet, allowances in formulation should be made to ensure that the minimum nutrient level is met after processing. †† Biotin does not need to be added unless diet contains antimicrobial or antivitamin compounds. ‡‡ Methionine may be used to substitute for choline as a methyl donor at rate of 3.75 parts for 1 part choline by weight when methionine exceeds 0.62%. *

1340

Appendix  III  AAFCO Dog and Cat Food Nutrient Profiles

presumed energy densities (3.5 kcal ME/g DM for dog foods, 4.0 kcal ME/g DM for cat foods). Since a dog or cat is presumed to eat less of a high-calorie food, the levels of the nutrients must be proportionally higher in order for the animal to meet its needs with lower food intake. Thus products very high in caloric density should also be corrected for energy content before comparisons with the profiles are made.

The AAFCO Dog and Cat Food Nutrient Profiles and accompanying information on using the tables are  published annually in the AAFCO Official Publication. Information on AAFCO and how to obtain a copy of the AAFCO Official Publication can be found on its website (http://www.aafco.org) or by writing to: Ms Sharon Krebs, AAFCO Assistant Secretary-Treasurer, P.O. Box 478, Oxford, IN 47971.

Index A AAFCO food nutrient profiles, 1337-1340 pet food and, XIII:74-75 Abamectin toxicity, 125-127 Abbott Cell-Dyn cytograms and histograms, XIII:388f, XIII:389-390, XIII:389f Abciximab, as antiplatelet therapy, 25 Abdomen acute (See Acute abdomen) alternatives to celiotomy, XIII:17-21 examination of, XIII:160-161 trauma to, causing pregnancy loss, 988 Abdominal pain, 67-72 Abdominocentesis, XIII:162-163 for ascites from liver disease, 557 for diagnosis of acute abdomen, 70-71 Abortion. See Pregnancy, termination of Abyssinian cat, amyloidosis in, 866 Acarbose, use of, in cats with diabetes mellitus, 204 Accuclot-D-dimer, 691 ACE inhibitor(s). See Angiotensin-converting enzyme (ACE) inhibitor(s) Acemannan for feline immunodeficiency virus, XIII:287 for feline leukemia virus, XIII:283 for feline retrovirus, 1280, 1281t Acepromazine adverse reactions to, in dogs, XIII:240t for agalactia, 1000t, 1001 for feline lower urinary tract disease, XIII:891 for laryngeal paralysis, 628 for tracheal collapse, 633 for urinary retention, 955, 956t opioids and, XIII:58 use of, XIII:122 in critical care, 88 Acetabular fractures, XIII:1030 Acetaminophen (Tylenol) for pain management, 12f-13f Heinz body anemia from, XIII:421 toxic exposure to, 97t toxicity of, 113, 114t, 568t, 569, XIII:210, XIII:218-219 Acetic acid ear therapy, 429, 430t shampoos, 414, 414t Acetylcholine (ACh) receptor testing, for myasthenia gravis, 488, 490, 1108, 1110-1111 Acetylcholine, for cholinesterase inhibitor toxicity, 115 Acetylcysteine (Mucomyst) for acetaminophen toxicity, 113, 114t, XIII:207t for aflatoxicosis, 158 for bacterial pneumonia, 662 for craniocerebral trauma, XIII:184 for keratoconjunctivitis sicca, XIII:1065 Acetylsalicylic acid. See Aspirin Acid-base balance. See also Acidosis; Alkalosis differential diagnosis of disorders of, XIII:108t in complicated diabetes mellitus, 218b in gastric dilatation-volvulus, 78-79 Acid-base disorders, 54-61 compensatory responses to, 55b, 55t

Page numbers followed by f indicate figures; t, tables; b, boxes.

Acid-base disorders (Continued) gaps and gradients in, 56b with acute renal failure, 881 Acidosis. See also Acid-base balance acid-base disorders and, 54-61, 60b differential diagnosis of, XIII:108t dilutional, 60, 60b hyperchloremic, 60b hyperkalemia and, XIII:375 in shock, XIII:145-146 organic, 60, 60b renal failure and, XIII:175 ACOPA I and II, XIII:472 Acorus calamus, 151t Acquired immunodeficiency diseases, XIII:516-520. See also EVOLVE Acral lick dermatitis causes of, 469b, XIII:552t diagnosis and treatment of, 468-473, XIII:551-556 Acral pruritic nodule. See Acral lick dermatitis Acromegaly hypertension and, 714t polyuria and polydipsia from, 847t ACTH testing. See Adrenocorticotropic hormone (ACTH) testing; Hyperadreno­ corticism; Hypoadrenocorticism Acthar gel (ACTH gel), 232 Actigal. See Ursodeoxycholic acid therapy Actinomyces spp., pyothorax from, 677, XIII:821 Actinomycin D (Cosmegen) administration protocol for, XIII:464 as chemotherapy, 310, XIII:469 for anal sac tumors, 384 in disseminated intravascular coagulation, XIII:192 Activated charcoal for flatulence, 526 use of, 112-113 Activated coagulation time (ACT) in disseminated intravascular coagulation, XIII:192 in rodenticide toxicosis, 117-118 Activated protein C (APC), for disseminated intravascular coagulation (DIC), 291 Acute abdomen differential diagnosis of, 68t, XIII:160-162, XIII:161t drainage techniques for septic, 72-76 evaluation and emergency treatment of, XIII:160-164 history with, 69b Acute respiratory distress syndrome (ARDS), use of glucocorticoids with, 1231-1232 Acyclovir, for feline herpesvirus, 1189, XIII:1059 Addison’s disease. See Hypoadrenocorticism Adenocarcinoma anal sac, 382-384, 467, 528 chronic colitis and, XIII:646 gastric, XIII:622-623 intestinal, XIII:623 lung, XIII:504t nasal, 352-353, 610b, 611f, 612f secondary orbital with, 1154 nasal and paranasal, XIII:501t ocular, 1156 of the larynx and trachea, XIII:503t

Adenocarcinoma (Continued) pancreatic, in cats, XIII:704 thyroid, benign, in cats, XIII:333 Adenoma, meibomian gland, 1183 Adenomatous polyps, XIII:623 Adenosine (Adenocard), for supraventricular tachyarrhythmias, 724-725, 725f, XIII:728-729 Adenoviral vectors, gene therapy and, XIII:497 Adenovirus, vaccination recommendations for, XIII:250 ADIC (Doxorubicin and Dacarbazine), XIII:473 Adnexal neoplasia, 1154-1155 Adrenal gland(s) disorders of (See Hyperadrenocorticism; Hypoadrenocorticism; Neoplasia) function tests of, 170-172, XIII:321-324 effects of nonadrenal disease on, XIII:362-363 (See also EVOLVE) hormone production in hyperadrenocorticism, 219, 221-223, 222t normal, 221, 400-401 tumors diagnosis and treatment of, XIII:368-371 (See also EVOLVE) differential diagnosis of, XIII:369t incidentally discovered, diagnosis and treatment of, XIII:368-371 (See also EVOLVE) noncortisol secreting, 222 Adrenal insufficiency during critical illness, 8, 228-230, 1231-1232 iatrogenic, 403 Adrenocorticotropic hormone (ACTH) testing effect on dexamethasone suppression test, XIII:321-322 effect on nonadrenal disease, XIII:362-363 (See also EVOLVE) for adrenal insufficiency, 229 for hyperadrenocorticism, 219-220 for hypoadrenocorticism, 231-233, XIII:374 interpretation of, 170-171, XIII:321 role of, in hyperadrenocorticism, XIII:364 with large pituitary tumors, XIII:367 Adverse reactions. See Allergy(ies); Drug reaction(s); Food allergy Aelurostrongylus abstrusus, 669 Aerokat spacer-mask, 656-657, 657f Aerophagia, causing flatulence, 524-525, 525b Aesculus hippocastanum, 151t Aflatoxicosis, 156-159 Agalactia, 1000t, 1001 AGEN canine D-dimer, 691 Agglutination, autoimmune hemolytic anemia and, XIII:429 Aglipristone, for canine pregnancy termination, 1032 AIHA. See Anemia, hemolytic Airway management, XIII:790-794. See also EVOLVE Airway obstruction, respiratory acidosis and, 58b Akita(s), sebaceous adenitis in, XIII:572-573 Alanine aminotransferase (ALT) abnormalities in, 544-545, 552 differential diagnosis of, XIII:109t in drug-associated liver disease, 567-569 in feline inflammatory liver disease, 577-581 in hepatic lipidosis, 571

1341

1342

  Index

Alapexy technique, 619 Albendazole for Filaroides hirthi, 668 for Paragonimus kellicotti, 671 Albumin. See also Human serum albumin solution colloid fluid therapy and, 63-64, XIII:66, XIII:67t concentration in inflammatory bowel disease, 505 Albuminuria, 861 Albuterol adverse effects of, 644, 655 for canine chronic bronchitis, 644 for feline asthma, 655, 657 for feline chronic bronchitis, 655 for tracheal collapse, 634 prior to nebulization therapy, 662 toxicity, XIII:154, XIII:154t Alcohol as antiseptic, XIII:260 toxicity of, XIII:226 Aldehydes, as antiseptic, XIII:261 Aldosterone, role of, 400 in polyuria and polydipsia, XIII:832 Aldosteronism, primary, XIII:369 Alkali burns, to eyes, XIII:1092 Alkaline phosphatase (ALP) abnormalities in, 544-545 differential diagnosis for increased, in dogs, 552b evaluation of elevated, in dogs, 549-553, 551f, 553b in drug-associated liver disease, 567-569 in feline inflammatory liver disease, 577-581 isoenzymes of, 545, 549-550 Alkalosis. See also Acid-base balance acid-base disorders and, 54-61 Allelic heterogeneity, XIII:911 Allerase for house dust mites, 427 shampoo, 412 Allergen(s). See also Allergen-specific immunotherapy; Drug Reaction(s) atopy (See Atopy) causing acral lick dermatitis, 470-471 contact, use of pentoxifylline with, 398-399 feline, hyposensitization of, XIII:567-568 schedule for, XIII:568t role of in development of hot spots, 447 in feline asthma and bronchitis, 652 in tracheal collapse, 631f, 633 to house dust mite, 425-427 to Malassezia, 454-455 Allergen-specific immunotherapy, 415-420 administration schedule, 416b, 417b, 418b adverse reactions to, 417-419 concurrent therapies with, 420 for feline atopy, 406 Allergic reactions. See also Drug reaction(s) to insulin, XIII:357 Allergic rhinitis, 610b, 613 Allergy testing acral lick dermatitis and, XIII:553 in-vitro, for atopy, XIII:565-566 intradermal, for feline atopy, XIII:565-566 Allergy(ies). See also Allergen(s) atopy (See Atopy) causing blepharitis, 1180 causing conjunctivitis, 1176 food (See Food allergy) testing for, with acral lick dermatitis, XIII:553 to insect bites, XIII:560 Allermyl shampoo, 411-412, 411t Allopurinol for leishmaniasis, 1253 for urate crystalluria, 854 Alloxan, for insulinoma, XIII:360 Ally-trenbolone (Regumate), 989 Alocetic, 430t Alopecia, canine melatonin therapy for, XIII:546-549 recurrent flank, XIII:546-547 type X, 222-223

Alpha-1-protease inhibitor, measurement of, XIII:642 Alpha-agonist(s) adverse effects of, 958 for urinary incontinence, 957t, 958 intoxications, XIII:153-157 Alpha-bromo-epiandrosterone, for feline infectious peritonitis, 1297t Alpha1-antagonist(s) for urinary incontinence and micturition disorders, 955 for urinary retention, 956t Alpha2-adrenergic agonist(s), for pain management, 13, 13t, 1128t, XIII:60 Alphaprostol, for abortion, XIII:952 Alprazolam, for urinary retention, 955, 956b Alternative medicine, for feline lower urinary tract disease (FLUTD), 945b Aluminum phosphate binders, 894 Alveolar-arterial oxygen gradient, 56, 56b Amanita, associated liver disease, 569 Amantadine, for pain management, 12f-13f Amatoxin, causing nephrotoxicity, 160b Ambulation, assisted, 1132 AMC 2 (Adriamycin, L-Asparaginase, Cyclophosphamide), XIII:472 AMD3100, for feline retrovirus, 1281t, 1283 American Animal Hospital Association, canine vaccine guidelines, 1272-1274, 1273t American Association of Feline Practitioners vaccine guidelines, 1275-1278, 1276t Ameroid constrictors, 584 Amikacin. See also Aminoglycoside(s) drug monitoring of, XIII:28t for Pseudomonas spp., 435t, XIII:264 for sepsis, XIII:273t intravitreal, 1148t minimum inhibitory concentrations of, XIII:35t subconjunctival, 1147t toxicity of, 162, XIII:214 Amino acid(s) essential, 167 for dilated cardiomyopathy, in dogs, 796 for heart failure, XIII:750 in nutritional support, 19, XIII:74 solutions of, for parenteral use, XIII:81t Aminocamptothecin (9-Aminocamptothecin), as chemotherapy, XIII:475-476 Aminoglycoside(s) for musculoskeletal infections, 1226t, 1229 for otitis, 435, 435t for Pseudomonas spp. aeruginosa, XIII:264 for sepsis, 1226t, 1229 toxicity of, XIII:214 causing vestibular signs, 1099 nephrotoxicity, 160b, 162 ototoxicity, 433b use of, in neutropenia, XIII:271 Aminophylline, for tracheal collapse, 634 Aminosalicylates, for chronic colitis, 518-519 Aminosyn II, 19 Amiodarone associated liver disease, 568t before cardioversion, 740 for supraventricular tachyarrhythmias, 726 for syncope, 712t for ventricular arrhythmias, 729, 796, XIII:736-737 in Doberman pinscher cardiomyopathy, 802 with heart failure, 775 toxicity of, 729-730, 775 use of, during CPR, 31 Amitraz adverse reactions of, in dogs, XIII:240t drug interactions with, XIII:92 toxicity of, 120b, 122, XIII:153, XIII:156, XIII:233-234 Amitriptyline for feline lower urinary tract disease, 945b, 946, 947t, XIII:889t, XIII:892 for feline pruritus, 408 for interstitial cystitis, in cats, XIII:895 for neurologic and musculoskeletal pain, 1128t for sensory mutilation, XIII:91, XIII:92t

Amlodipine for heart failure, 775 for hypertension, XIII:101, XIII:840 systemic, 715-716 with hyperthyroidism, 276t with renal disease, 912, 912t for myocarditis, 806 for refractory heart failure, XIII:754 for syncope, 712t Amyloidosis, 866-867 Ammilide, toxicity of, 165 Ammiline, toxicity of, 165 Ammonia and ammonium urate urolithiasis, XIII:872 in hepatobiliary disease, XIII:661 Ammonia testing in hepatic lipidosis, 571 in hepatobiliary disease, 547 in portosystemic shunts, 583, 586 Ammonia tolerance testing, 583 Ammonium chloride, for feline lower urinary tract disease, XIII:889t Ammonium urate compound uroliths with, XIII:876-877 crystalluria, 851t, 853-854, 854f uroliths, in dogs with portosystemic shunts, XIII:872-874, XIII:873f Ammunition, 127 Amorphous urate crystalluria, 851t Amoxicillin adverse reactions to in cats, XIII:241t in dogs, XIII:240t associated liver disease, 568t for Bartonella spp. infections, XIII:306 for Enterococci spp. infections, XIII:265 for feline calicivirus, 1286 for feline lower urinary tract disease (FLUTD), 946 for Helicobacter spp. infection, 495-496, 495f for neutropenia, XIII:269t for urinary tract infections, 920-921, 920t, 921t, 1226, 1226t Amoxicillin-clavulanate for bacterial pneumonia, 661, 661t, 1226t, 1228 for musculoskeletal infections, 1226t, 1228-1229 for neutropenia, XIII:269t for pyoderma, 1226t, 1227 for pyothorax, 677 for upper respiratory tract infections, 1226t for urinary tract infections, 920-921, 920t, 921t, 1226, 1226t for vaginitis, 1010-1011 minimum inhibitory concentrations of, XIII:35t Amphetamine toxicity, 144-145 Amphimerus pseudofelineus, 542-543, XIII:705 Amphotericin B causing nephrotoxicity, 160b for central nervous system cryptococcosis, 1072-1073 Ampicillin crystalluria, 851t for Enterococci spp. infections, XIII:265 for leptospirosis, 1239 for sepsis, XIII:273t for urinary tract infections, 920-921, 920t, 921t, 1226, 1226t minimum inhibitory concentrations of, XIII:35t Ampicillin-sulbactam (Unasyn) for pyothorax, 677 for sepsis, XIII:273t Amplatzer vascular plug, 745-746, 745f Amplatz canine ductal occluder, 745-746 Amputation, for osteosarcoma, 360 Amylase, in abdominal fluid, 71 Amyloidosis, glomerulonephritis and, in dogs, XIII:851 Anal atresia, 1014 Anal furunculosis. See Perianal fistulas Anal glands. See Anal sac(s)

Anal sac(s) diseases of, 465-468 impaction of, 466-467 normal function and structure of, 465-466 tumors, 382-384, 467, 528 Anal sacculitis, 467, 528 Anal-rectal disease, diagnosis and treatment of, 527-531 Analgesia epidural, XIII:126-131 (See also EVOLVE) for feline lower urinary tract disease, 945b, 947t, 948 for mechanical ventilator support, 607-608 for pancreatitis, 536, 540 for treatment of acute pain, 11-17 intravenous techniques for, 88-89 pain management and, 9-17, XIII:57-61 Anaphylaxis cutaneous eruptions and, XIII:556-559 from allergen-specific immunotherapy, 419 Anaplasmosis causing nonregenerative anemia, 272 diagnosis and treatment of, 1249-1251, 1250f thrombocytopenia from, 282t, 1249 Anaplastic carcinoma lung, XIII:504t of the larynx and trachea, XIII:503t Andersonstrongylus (Filaroides) milksi, 669 Androgen(s), 400 for estrus suppression, 1025-1026 for false pregnancy, 991 Androgen-dependent masculinization, 1038 defects in, XIII:907 Androstenedione, role of, in hyperadrenocorticism, 221-223, 222t Anemia aplastic, 274 causing syncope, 710, 710b erythrocyte morphologic characteristics of, XIII:381-383 erythropoietin for, 916-917, 1280 feline, disorders of, XIII:421-424 (See also EVOLVE) from chronic kidney disease, 874t, 877, 890t treatment of, 914-918 from uremia, XIII:865 Heinz body, XIII:421-423 (See also EVOLVE) hemolytic autoagglutination of RBCs, on scattergrams and histograms, XIII:383 autoimmune aspirin for, 25 blood-typing and, 261, XIII:397 complications of, 270-271, XIII:433 diagnosis and treatment of, 266-271 feline, XIII:430 nonregenerative, 273-274 pathophysiology of, XIII:427-428 risk for pulmonary thromboembolism with, 696 causes of, 267b clinical signs of, 267b from mycoplasmosis, 1245-1248 laboratory findings with, 267t, XIII:429t hereditary erythrocyte disorders causing, XIII:414-420, XIII:416t (See also EVOLVE) iron deficiency, 915-916 macrocytic, in cats, XIII:423-424 methemoglobinemia and, XIII:422-423 nonregenerative, 272-276 causes of, 272-276 diagnostic approach to, 273b of hypothyroidism, XIII:328 of inflammatory disease, 272 problems blood-typing with, 261 Anesthesia. See also Propofol; specific agents epidural, XIII:126-131 (See also EVOLVE) esophagitis and, XIII:607 for emergency and critical care procedures, XIII:122-126 for intracranial tumors surgery, 1078-1079 for status epilepticus, 1063f, 1064 local for pain management, XIII:60 in critical care, XIII:124

  Index Anesthetic(s) associated esophageal reflux, 482-483 for interluminal tracheal stenting, 640 intravenous techniques, 88-89 local, 14-16 regional, 14-16 techniques for early age neutering, 1022-1023 to evaluate laryngeal function, 627-628 to obtain airway control, 600 Anestrus, in dogs, 978, XIII:926 and estrus suppression methods, 1024-1030 Angiogenesis, in canine hemangiosarcoma, 328 Angiography pulmonary, 692 with PDA devise occlusion, 745-746, 746f Angiotensin. See Renin-angiotensin-aldosterone system Angiotensin-converting enzyme (ACE) inhibitor(s) adverse effects of, 794-795, 855, 856b effect of, XIII:712-713 for asymptomatic valvular disease, 783 for chronic kidney disease, 874t, 877-878, 885, 912 for dilated cardiomyopathy, in dogs, 794-795, 794t for Doberman pinscher cardiomyopathy, 802 for feline cardiomyopathy, 811-814, 811t, 818, XIII:763-764 for heart failure, 772-775, 779t, 784 for nephritis, XIII:852 for outpatient heart failure, XIII:748 for proteinuria, 862 for refractory heart failure, XIII:753-754 for syncope, 712t for systemic hypertension, 715-716 interactions of, with nutrients, XIII:712-713 with furosemide, 783-784 with progressive renal failure, XIII:863 Animal cruelty, and poisoning, 105-108 Anion gap, 55-56, 56b Anisocoria, causes of, 1168-1174, 1168f, 1169f, XIII:1045-1050 Anorexia adverse effects of, XIII:70t from stomatitis and faucitis, in cats, XIII:600 from uremia, XIII:864, XIII:864t hepatic lipidosis and, XIII:686 hypokalemia and, XIII:687 microenteral nutrition for, XIII:136-140 (See also EVOLVE) refeeding syndrome and, XIII:87-89 therapy of, XIII:69-74 Anovulvar cleft, 1013 Anterior uvea drug therapy for, 1146-1148 neoplasia of, 1156 in cats, XIII:1095-1096 in dogs, XIII:1095 Anterior uveitis. See Uveitis Anti-interleukin-5 antibody, for feline asthma, XIII:809 Antiarrhythmic(s) drugs. See also specific drug or disease for cats, 738 for CPR, 31 for Doberman pinscher cardiomyopathy, 802-803 for supraventricular tachyarrhythmias, 723-726, 725f with dilated cardiomyopathy, in dogs, 795-796 with heart failure, 775, 777-778, 779t Antibiotic therapy. See also Antifungal drug(s) as potential nephrotoxins, 856b, XIII:855b bacterial resistance and, XIII:262-267 (See also EVOLVE) combination, XIII:38-39 for febrile neutropenics, XIII:270t criteria for selection of, XIII:33t distribution of, XIII:37 do’s and don’ts of, XIII:33-40 efficacy of, effects of the microenvironment on, XIII:37t empiric, 1225-1229, 1226t for shock, 7

1343

Antibiotic therapy (Continued ) fluorinated quinolones as, use and misuse of, XIII:41-48 for acral lick dermatitis, 471 for bacterial pneumonia, 661, 661t for brucellosis, 986 for canine chronic bronchitis, 644, XIII:804 for cholangiohepatitis, XIII:673 for endocarditis, XIII:770-771 for feline asthma, 655-656, XIII:808-809 for feline chronic bronchitis, 655-656 for feline lower urinary tract disease, XIII:889-891 for gastric dilatation-volvulus, 79, 81 for infective endocarditis, 788t, 790-791 for neutropenia, XIII:267-272, XIII:268 for open fractures, 84, XIII:171 for otitis externa, 429, 431t, 435 from Pseudomonas, XIII:587, XIII:587t for pancreatitis, 537, 540 for parvovirus, XIII:630-631, XIII:631t for pyothorax, 677 for pyotraumatic dermatitis, 448, XIII:551 for rhinitis, 615, 617-618 for sepsis, XIII:271-275 for septic metritis, 1000 for shock, XIII:145 for small intestinal bacterial overgrowth, XIII:640 for stomatitis, in cats, XIII:601 for urinary tract infections, 920-921, 920t, 921-925, 921t, XIII:885t multidrug resistant, 921-925 general spectrum of, XIII:145t intravitreal, 1148, 1148t methicillin-resistant canine, 449-450 minimum inhibitory concentrations (MIC) of, XIII:35t ototoxic, 433b prophylactic, in breeding bitches, 982, 987 subconjunctival, 1146, 1147t tylosin-responsive diarrhea, 506-509 urine collection and, XIII:15 with endocrine disorders, XIII:879-880 Antibody test(s) anti-EPO, 917 for feline heartworm disease, 833-834 for heartworm disease, in cats, XIII:784-785 for leptospires, XIII:308-309 Antibody(ies) detection of, using ELISA, XIII:10-11 immunophenotyping and, in the dog, XIII:505-509 Anticancer drugs and protocols new drugs, 311-314 traditional drugs, 305-311 Anticholinergic(s) for feline idiopathic cystitis, 947t, 948-949 for lower urinary tract disease, XIII:899-902 Anticoagulant rodenticides. See Rodenticide toxicity Anticoagulant therapy, 24-28, 289f during hemodialysis, 897-898 for disseminated intravascular coagulation (DIC), 291 for prevention of thrombi, 693-695 Anticonvulsant therapy. See also Epilepsy; Seizure(s) for seizures from intracranial tumors, 1079t, 1082 for status epilepticus, 1063f, 1064 for traumatic brain injury, 35t in cats, XIII:965-966 interaction of with cisapride, XIII:616 with metoclopramide, XIII:616 new drugs as, 1066-1069 toxicity of, XIII:217 Antidepressant(s), for feline lower urinary tract disease (FLUTD), 945b, 946, 947t Antidiuretic hormone response test, XIII:834 role of, in polyuria and polydipsia, 844-846

1344

  Index

Antidote(s) for toxicities, 112-116, 114t, XIII:207t supplies, 98, 98f Antiemetic(s) for chronic kidney disease, 873t, 877 for parvoviral enteritis, XIII:631 Antifibrotics, for hepatic support, 556 Antifreeze. See Ethylene glycol toxicosis Antifungal drug(s), XIII:815-819. See also ­specific condition or drug cream, toxicity of, XIII:230 for central nervous system infection, 1072-1073 for dermatophytosis, 459t, 460-461 for otitis externa, 429, 431t, 435t Antigen receptor rearrangements (PARR), for canine lymphoma, 338, 338t Antigen testing detection of, using ELISA, XIII:11 for canine heartworm disease, 838, 841-842, XIII:777-779 for feline heartworm disease, 833, 835, XIII:784 for leishmaniasis, 1253 to house dust mites, 426 Antigen(s) selection of, for vaccination, XIII:251 to house dust mites, 426 Antihistamine(s) adverse effects of, XIII:51-52 effects of, XIII:49-50 for vestibular disease, 1101 in cats for atopic disease, XIII:566-567 for pruritus, 408, XIII:543, XIII:544t oral doses of, XIII:566t toxicity of, XIII:229 use of, XIII:48-53 Antihypertensive therapy, 713-717, XIII:838-841 Antiinflammatory drug(s). See also specific drug or drug type for cervical vertebral instability, XIII:995t for chronic bronchitis, 643 for chronic colitis, 518-519, 519t for feline lower urinary tract disease, 945b, 948, XIII:891-892 for inflammatory bowel disease, 505 for otitis externa, 429-430, 432t for pancreatitis, 537, 540 for protein-losing enteropathy, XIII:643 glucocorticoids as, 400-405, 403b dosage of, 404 topical, XIII:554 Antileukotrienes, for feline airway inflammation, 656 Antimetabolites as chemotherapy, XIII:467-468 for papillomaviruses, XIII:570-571 Antimicrobial resistance, avoidance of, XIII:37-38 Antimicrobial shampoos, 413-415, 414t for pyotraumatic dermatitis, 447 Antimicrobial therapy. See also Antibiotic therapy; Antifungal drug(s) as potential nephrotoxins, 856b empiric, 1225-1229, 1226t for chronic colitis, 518-519, 519t for feline lower urinary tract disease, 945-946, 945b for inflammatory bowel disease, 505 for prostatitis, 1048 for shock, 7 for urinary tract infections, 920-921, 920t, 921t minimum inhibitory concentration (MIC) with, 920 Antimuscarinic agents, for lower urinary tract disease, XIII:900-902, XIII:900t Antineoplastics, causing nephrotoxicity, 160b Antinuclear antibody (ANA) test, for systemic lupus erythematosus, XIII:515 Antioxidants for canine dilated cardiomyopathy, 708, 796 for heart disease, XIII:715 for hepatic support, 554-555 for pancreatitis, 537

Antiplatelet therapy, 24-28 for prevention of thrombi, 694-695 Antiprogestin(s), for abortion, XIII:951, XIII:953f Antiprolactin drug(s), for false pregnancy, 991 Antiprostaglandin(s), for shock, XIII:145 Antipruritic drugs, topical, XIII:554 shampoos, 411t Antiseborrheic shampoos, 412-413, 412t Antiseptic(s) for reducing hospital-acquired infections, 1223-1224 in small animal practice, XIII:258-262 Antisera, for shock, XIII:146 Antispasmodic(s), for feline lower urinary tract disease, 945b, 947t, 948-949 Antithrombin effect of, heparin on, 693 for disseminated intravascular coagulation (DIC), 291 role of, in disseminated intravascular coagulation, 288f, XIII:192-193 values of, to guide DIC therapy, XIII:193t Antithrombin III assay, 692 Antithyroglobulin antibodies, 189 Antithyroid drug(s), 175-179, 176t Antitumor antibiotics, 310 as chemotherapy, XIII:468-469 Antitussive agents for chronic bronchitis, 644-645, XIII:803-804 for tracheal collapse, 634, XIII:799-800 Antivenins, XIII:210 Antiviral drug(s) for feline herpesvirus, 1188-1190 for feline retrovirus, 1281t, 1282-1283 for feline rhinitis, 618 for papillomaviruses, 445-446, XIII:571 Anuria definition of, XIII:14t with acute kidney failure, 879-881, 880t, XIII:175-176 Anxiolytics(s), for feline lower urinary tract disease (FLUTD), 945b, 946, 947t Aortic body tumor, 356-357, 826 Aortic insufficiency, from infective ­endocarditis, 786-791 Aortic stenosis causing syncope, 710b, 711t in cats, XIII:739t, XIII:740t Aortic thromboembolism (ATE). See Thromboembolism Apocrine gland adenocarcinoma, of anal sac, XIII:593 Apomorphine, for toxicity, 96, 97f, 113t Apoptosis related multiple drug resistance, XIII:481 Appetite stimulants, in nutritional support, 23 Aprotinin (Trasylol), for pancreatitis, XIII:699 Aqueous flare, 1142, 1142f, 1200 Aqueous humor misdirection syndrome, in cats, 1213-1214, 1213f, 1214f opacification of, causing blindness, 1165, XIII:1038-1039 paracentesis, 1202, 1203f role in glaucoma, 1207-1208, 1208b Arachidonic acid metabolism, inhibitors of, 1129-1130, 1129f Arcus lipoides corneae, XIII:1069 Argasids as vectors, XIII:297 diseases associated with, XIII:297t Arginine for feline herpesvirus, 441 for heart failure, 774-775, 779t Armoise essential oil, 152t Arnica spp., 151t Arrhythmia(s). See also Electrocardiography ablation, XIII:730 accelerated idioventricular, XIII:731 bradyarrhythmias, XIII:719-725 cardioversion for, 739-743 causing syncope, 709-712, 710b, 712t evaluation of, in cats, XIII:101

Arrhythmia(s) (Continued ) from diuretic therapy and nutrient ­restriction, XIII:712 in cats, 731-739 from hyperthyroid heart disease, XIII:718 with congenital heart disease, XIII:741 in heart failure, 775, 777-778 pacemakers for. See (Pacemaker(s)) sedation with, XIII:776t, XIII:778 supraventricular tachyarrhythmias (SVT), XIII:728-729 diagnosis and treatment of, 722-727, 724f, 725f, 725t in cats, 733t tachyarrhythmias, with feline myocardial diseases, XIII:763 testing for, 711 ventricular cardioversion for, 743 causing syncope, 711, 711t, 712t deciding to treat, XIII:730-733 diagnosis and treatment of, 727-731, XIII:733-737 ectopic beats, XIII:730-733 in cats, 733t, 737-738, 738f, 818 in Doberman pinschers, 800-803, XIII:759-760 monitoring therapy of, 730 therapy of, XIII:718 with arrhythmogenic right ventricular cardiomyopathy, 728 with boxer cardiomyopathy, 798-799 with dilated cardiomyopathy, 728, 795-796 with gastric dilatation-volvulus, 79, XIII:166 with heart failure, 775 ventricular fibrillation algorithm for management of, XIII:152f defibrillation for, XIII:150-153 defibrillation for, during CPR, 30 with Doberman pinscher cardiomyopathy, XIII:757f, XIII:759-760 Arrhythmogenic right ventricular ­cardiomyopathy in cats, 807-808 in dogs, 728, 797-799 Arsenic, causing nephrotoxicity, 160b Art and craft product poisoning, incidence of, XIII:206t Arterial blood gas. See Blood gas(es) Arterial blood pressure. See Blood pressure Arterial catheters, 39-43 access procedure, 40b complications of, XIII:121t cutdown techniques for, 41-43, XIII:119-121 maintenance and complications of, XIII:121 Arterial thromboembolism. See Thromboembolism Arteritis, with steroid responsive meningitis, in dogs, XIII:978-981 Artificial insemination, in dogs, XIII:916-917 Arytenoid cartilages laryngeal paralysis and the, 627-628 lateralization of, 628, 629, 635 Arytenoidectomy, partial, 621, 628-629 Asacol, 519 Ascarid(s). See Parasite(s) Ascites, from liver disease, 556-557, XIII:661 Ascorbic acid. See Vitamin C Aspartate aminotransferase (AST), abnormalities in, 544-546, 552 Aspergillosis nasal, 610b, 613-614 treatment of, XIII:315-317 ocular signs of, XIII:279 respiratory tract, XIII:815-819 treatment of, XIII:272 Aspergillus spp., causing aflatoxicosis, 156-159 Aspermia, 1049-1052 Aspiration pneumonia. See Pneumonia, aspiration

Aspirin as antiplatelet therapy, 24-25 causing nephrotoxicity, 162 drug monitoring of, XIII:28t for anterior uveitis, 1206t for aortic thromboembolism, 814, 823-824, XIII:767 for disseminated intravascular coagulation (DIC), 291 for endocarditis, XIII:771 for glomerulonephritis, in dogs, XIII:852 for neurologic and musculoskeletal pain, 1128t for osteoarthritis, XIII:1019 for prevention of thrombi, 694-695 side effects of, XIII:214-215 Assays, in vitro, for atopic disease, XIII:560-564, XIII:561t Assistive devices, for physical therapy, 1133 Asthma, feline, 650-658, XIII:805-810 vs. cardiomyopathy, 812 Astringents, for topical treatment of hot spots, 448 Atenolol for beta-agonist toxicity, XIII:155 for feline cardiomyopathy, 811-813, 811t for feline myocardial disease, XIII:764 for feline ventricular tachyarrhythmias, 738 for heart failure, 772-775 for hypertension, XIII:840 with renal disease, 912t, 913 for hyperthyroidism, 176t, 178-179, XIII:337 for mitral valve dysplasia, 768 for pulmonic stenosis, 752 for subaortic stenosis, 760 for systemic hypertension, 716 for ventricular tachyarrhythmias, in boxers, 799 Atherosclerosis, from hypothyroidism, XIII:328 Atlantoaxial subluxation, 1083-1087, 1084f, 1085f, 1086f Atopic dermatitis. See Atopy Atopy allergen-specific immunotherapy for, 415-420 and acral lick dermatitis, 470, XIII:553 and anal gland function, 466 blepharitis from, 1180 control of dust mite allergies for, 425-427 cyclosporine for, 255, 386-388, 421 diagnosis and treatment of, with in vitro assays, XIII:560-564 essential fatty acids for, XIII:540-541 feline, 406, XIII:560-563, XIII:564-569, XIII:565t therapy of, 406, XIII:544-545 hypoallergenic diets for, 395-397 interferons for, 389-390 nutritional supplements for, 396 otitis externa from, 428 pentoxifylline for, 399 shampoo therapy for, 411-412, 412t topical immune modulators for, 421-422 Atovaquone, for babesiosis, 1289t, 1290 Atracurium, for mechanical ventilator support, 608 Atresia ani, 527-528 Atrial fibrillation, XIII:729 cardioversion for, 739-743, 742f causing syncope, 711t, 712t in cats, 732, 737, 737f with dilated cardiomyopathy, in dogs, 795 with heart failure, 775 Atrial flutter, cardioversion for, 739-743, 743f Atrial myocarditis, 808 Atrial premature complexes (APC), in cats, 737f Atrial septal defect feline, XIII:739t, XIII:740t surgery for, XIII:747 Atrial standstill in cats, 735, 735f persistent, XIII:721-722, XIII:721f Atrial tear, with valvular heart disease, 785

  Index Atrioventricular (heart) block, XIII:722, XIII:722f causing syncope, 710, 710b, 711t, 712t in cats, 733t, 734-735, 734f, 735f permanent cardiac pacing for, 717-721 transvenous pacing for, XIII:198 Atropa belladonna, 151t Atropine for anterior uveitis, 1206, 1206t for cholinesterase inhibitor toxicity, 114t, 115, 120 for organophosphate toxicity, XIII:207t subconjunctival, 1147t use of, XIII:125t Atropine response test, XIII:723 Auditory system, anatomy and physiology of, XIII:971-972 Auscultation. See also Heart murmur(s) abdominal, 69 with thoracic trauma, 86 Australian shepherd(s), avermectin toxicosis in, 125-127 Autoagglutination blood-typing and, 261, XIII:397-398 from immune-mediated hemolytic anemia, 267-268 of red blood cells, on scattergrams and ­histograms, XIII:383 Autoantibodies, to thyroid hormone, 172, 189 Autoimmune disease. See Anemia, hemolytic; Thrombocytopenia Automotive product poisoning diagnosis and treatment of, 130-135 exposure to, 93-94 incidence of, XIII:206t Autonomic nervous system, role of, in ventricular arrhythmias, XIII:734 Autosomal dominant inheritance, in dogs, XIII:909 Autosomal recessive inheritance, in dogs, XIII:909-910, XIII:910t Avermectin(s) toxicosis, diagnosis and treatment of, 125-127 use of, in dermatology, 390-394 Axonal degeneration, 1115-1116 Axonal reflex, 1171 Azathioprine (Imuran) as immunosuppressive agent, 254 associated liver disease, 568t for autoimmune myasthenia gravis, 1109 for chronic colitis, 519t, 520 for episcleritis, in dogs, 1191t, 1192 for immune-mediated hemolytic anemia, 270, XIII:432 for inflammatory bowel disease, 505 for ocular diseases, 1152t, 1153 for perianal fistulas, 529 for thrombocytopenia, 286t, XIII:440 in dermatology, XIII:536 use of, XIII:510 Azithromycin associated liver disease, 568t for babesiosis, 1289t, 1290 for bacterial pneumonia, 661, 661t, 1226t, 1228 for idiopathic pleural effusion, 684 for idiopathic rhinitis, 615, 618 for toxoplasmosis, 1256 for upper respiratory tract infections, 1226t, 1228 Azotemia. See also Renal disease; Renal failure causes and risk factors for, 856b diagnostic approach to, 855-860 B Babesia spp., overview of, 1288, 1289t Babesiosis causing azotemia, 856b, 857 diagnosis and treatment of, 1288-1291, 1289t relationship to Bartonella spp. infection, XIII:301t thrombocytopenia from, 283t, XIII:440, XIII:441t vector associated with, XIII:296t

1345

Bacille Calmette-Guérin, for feline retrovirus, 1281t, 1282 Bacillus piliformis, causing neonatal diarrhea, XIII:626, XIII:627t Bacillus thuringiensis israelensis ingestion, 111 Bacitracin, adverse reactions of, in cats, XIII:241t Baclofen, for urinary retention, 956t Bacteremia endocarditis and, XIII:768-769 thrombocytopenia from, XIII:441t Bacteria anaerobic, XIII:266 Bordetella bronchiseptica, 646-649 causing anterior uveitis, 1203b, 1204 causing conjunctivitis, 1177 causing encephalitis and meningitis, 1071-1072 causing infective endocarditis, 788-790, 788t causing myocarditis, 804, 805t causing pneumonia, 658-660, 659b, XIII:812-815, XIII:813t causing pregnancy loss in the queen, 1044-1045 causing prostatitis, 1047-1048 causing septic metritis, 1000-1001 causing urinary tract infections, 918-919, 920t, 921-922 in cats, XIII:880-882 virulence of, in difficult, XIII:883-884 coliform, diagnosis and treatment of, XIII:266 disinfectants and antiseptics against, XIII:259t empiric antimicrobial therapy for, 1225-1229, 1226t feline Chlamydia spp., 1185-1187 Helicobacter spp., 492-497, 494f, 495f in cholangiohepatitis, XIII:672 in homemade pet foods, 166 in pet foods, XIII:237 incriminated in disseminated intravascular coagulation, XIII:191t neonatal diarrhea from, XIII:627t overgrowth of, in small intestine, XIII:637-641 (See also EVOLVE) resistance of, XIII:262-267, XIII:263t (See also EVOLVE) translocation of, XIII:201-203 (See also EVOLVE) vaginal, 980-981, 981t, 982t, 987, 987b Bacteriuria, 918 Bacteroides spp. resistant infections of, XIII:266 sepsis and, XIII:273 Baermann fecal examination, for respiratory parasites, 667-671 Balloon valvuloplasty for pulmonic stenosis, 755-756 for subaortic stenosis, 760-761 for tricuspid valve dysplasia, 764 Ballooning of esophageal stricture, 485 of pericardium, 830 Banamine, for topical treatment of lick ­dermatitis, 472 Barbiturate(s) anesthesia, for status epilepticus, 1063f for craniocerebral trauma, XIII:181t, XIII:184 toxicity of, 146 Barden’s sign, 1121-1122 Barium for assessment of gastrointestinal motility, XIII:612-613 for esophageal evaluation, 483, 489, 491, XIII:608 for megaesophagus diagnosis, XIII:604 Baroreceptor reflex, causing syncope, 709 Bartonellosis B. vinsonii, in dogs, XIII:300-302, XIII:301t causing anterior uveitis, 1203b, 1204 diagnosis and treatment of, 1241-1245 endocarditis and, XIII:768-769 feline, XIII:302-307

1346

  Index

Bartonellosis (Continued ) myocarditis from, 808 polymerase chain reaction for, XIII:248-249 role in infective endocarditis, 788-790, 788t thrombocytopenia from, 283t, XIII:441t Basal energy requirements, parenteral nutrition and, XIII:89 Basal metabolic rate, for monitoring therapy of hypothyroidism, XIII:332-333 Basenji(s), enteropathy of, XIII:642 Basophil cytogram, XIII:383-384, XIII:385f Bayer (Technicon) H-1 cytograms and ­histograms, XIII:381f, XIII:384-389 Bedlington terrier, inherited copper hepatitis in, 557-562 Bee and hymenoptera stings. See Bite(s) Behavior disorders of compulsive, XIII:92t mutilation problems of, XIII:90-93 effect of early neutering on, 1021 with intermittent erection in male castrated dogs, 1053 Belching, 523-527 Belgian shepherd(s), gracilis-semitendinosus myopathy in, XIII:989-992 Benazepril adverse effects of, 794-795 for dilated cardiomyopathy, in dogs, 794-795, 794t for feline cardiomyopathy, 811t, 813 for heart failure, 772-774, 784 for hypertension, 716, XIII:840 in cats with hyperthyroidism, 276t with kidney failure, 912, 912t for syncope, 712t Bence Jones proteins, 860-861 Benign prostatic hypertrophy, 1046-1047 Benzodiazepine(s). See also Diazepam; ­Midazolam cocktail with opioids, 11 drug monitoring of, XIII:28t for appetite stimulation, 575 for urinary retention, 955, 956t use of, XIII:123 Benzopyrene drugs, 679 Benzoyl peroxide shampoo, 412t, 413. See also Shampoo therapy for pyoderma, 413, 414t Benzyl benzoate, for house dust mite control, 426-427 Beta-adrenergic agonists, for feline glaucoma, 1210t, 1211 Beta-adrenergic blockers for canine glaucoma, XIII:1079 for dilated cardiomyopathy, in dogs, 796 for feline cardiomyopathy, 811-814, 811t for feline glaucoma, 1210t, 1211 for heart failure, 772-775, 779t, 784 for hypertension with renal disease, 911-912 for mitral valve dysplasia, 768 for myocarditis, 806 for pulmonic stenosis, 755 for subaortic stenosis, 760 for supraventricular tachyarrhythmias, 725f for syncope, 711-712 for ventricular arrhythmias, XIII:735-736 with Doberman pinscher cardiomyopathy, 802 with hyperthyroidism, 176t, 178-179, 182, XIII:336-337 Beta-agonist intoxications, XIII:153-157 Beta2-agonists adverse effects of, 644 for chronic bronchitis, 644, XIII:803 for feline chronic bronchitis or asthma, 654-655 Betamethasone adverse reactions of, in dogs, XIII:240t comparison of, to other glucocorticoids, 401t for ocular diseases, 1150t, 1151 subconjunctival, 1147t, 1206t topical otic, 432t Betaxolol, for feline glaucoma, 1210t, 1211

Bethanechol for feline lower urinary tract disease, XIII:889t for megaesophagus, 491 for urinary retention, 955, 956t Bicarbonate acid-base disorders and, 54-61 use of, in gastric dilatation-volvulus, 78-79 Bicipital tenosynovitis, in dogs, XIII:1014-1018 Biguanides, as disinfectant, XIII:259-260 Bile acid(s) as hepatotoxins, 563, XIII:691 in feline inflammatory liver disease, 577-581 in hepatic lipidosis, 571 in hepatobiliary disease, 546-547, 552-553, XIII:661 in hepatoportal microvascular dysplasia, XIII:682, XIII:683f in portosystemic shunts, 582-583, 586 measurement of, for small intestinal bacterial overgrowth, XIII:640 metabolism, 563-564 ursodeoxycholic acid therapy, 563-565 Bile aspirates, 577 Biliary mucocele, in dogs, 587-589, 587f Biliary tract disease, and feline inflammatory liver disease, 576-581 Bilirubin. See also under Hepatic; ­Hyperbilirubinemia; Liver disease crystalluria, 851t, 852, 852f elevation of, with sepsis, XIII:669 hepatobiliary disease and, XIII:660 in abdominal fluid, 71 in drug-associated liver disease, 567-568 in feline inflammatory liver disease, 577-581 in hepatobiliary disease, 546 Bilirubinuria autoimmune hemolytic anemia and, XIII:429 hepatobiliary disease and, XIII:660 Biochemical measurements. See Laboratory test(s) Biochemical tests for canine hereditary disorders, 1054 of cerebrospinal fluid, in cats, XIII:1223t Biologic response modifiers, as chemotherapy, XIII:476-477 Biomarkers, of heart disease, 783 Biopsy bone, 359 conjunctival, 1195 endomyocardial, 805-806 gastric, for Helicobacter spp., 493-494, 495f incisional vs. excisional, 321-322 intestinal for colitis, 521, 522f for inflammatory bowel disease, 503 kidney, 858-859, 864 in acute renal failure, XIII:174 liver, 548-549, 559, 571, XIII:671 for hepatoportal microvascular dysplasia, XIII:684-685 techniques for, XIII:662-663 lower urinary tract, XIII:886-888 lung, 673 nasal, 352, 611-612 nasopharyngeal, 623 pancreas, 535 sampling guidelines for, XIII:452-453 skin, for acral lick dermatitis, 470 testicular, XIII:946 Biotin deficiency, differential diagnosis for, in cats, XIII:565t Birth control pill ingestion, 148-149, 148t-149t Bisacodyl, for constipation, in cats, XIII:650, XIII:651t Bismuth compounds for flatulence, 526 for Helicobacter spp. infection, 495t, 496 Bisphosphonates for hypercalcemia of malignancy, 346f, 347 for idiopathic feline hypercalcemia, 239-240 for osteosarcoma, 362 Bite(s), and sting poisoning, incidence of, 9495, 97t, XIII:206t Bitolterol, toxicity, XIII:154, XIII:154t Bitter almond essential oil, 152t

Bladder stone(s). See Urolithiasis Bladder, urinary. See also Cystitis; Feline lower urinary tract disease atonic, urinary tract infection and, XIII:885 cancer of, 369-373 forceps biopsy of, XIII:886-888 function of, with sacral trauma, XIII:1023 methods for emptying, XIII:15t parasympathetic innervation to, XIII:900f polyps, 979 trauma of, XIII:850 Blastomycoses diagnosis and treatment of, 1265-1267, 1266t, 1267t ocular signs of, XIII:278 respiratory tract, XIII:815-818, XIII:816f Bleach. See Sodium hypochlorite (Bleach) Bleeding disorders, 277-280. See also ­Hemorrhage; Hemostasis from renal failure, 914-915 Bleeding time, with von Willebrand’s disease, XIII:435 Bleomycin, as chemotherapy, XIII:469 Blepharitis, XIII:1051-1052 diagnosis and treatment of, 1178-1184 tear film disturbances causing, 1194 Blindness causes of, 1163-1167 diagnosis of, XIII:1038-1041 normal visual pathways, 1169f pain and, with glaucoma, XIII:1080-1081 with anisocoria, 1168-1174 Blood. See also Blood transfusion comparison of Oxyglobin and, XIII:426 components, characteristics of, 63t crossmatching of, 263-265, XIII:398-399, XIII:401 evaluation of, during 24 hour urine ­collection, XIII:14-15 products, for transfusion, XIII:402 Blood collection in cats, in critical care, XIII:102 vascular access techniques for, XIII:118-121 via arterial catheter, 42 Blood culture(s) for Bartonella spp., 1243, XIII:301-302, XIII:305-306 for Brucella canis, 986 for endocarditis, 786-790, 788t, XIII:768-770 for neutropenia and fever, XIII:268-270 Blood dyscrasias, from methimazole, 175 Blood gas(es). See also Acid-base balance; Acidosis; Alkalosis interpretation of, with acid base disorders, 54-61 to determine oxygen effectiveness, 600 to determine oxygen needs, 597 with chronic bronchitis, 643 with interstitial lung disease, 673 with noncardiogenic pulmonary edema, 663-664 with pulmonary thromboembolism, 691 Blood glucose. See Diabetes mellitus; ­Hyperglycemia; Hypoglycemia Blood glucose monitoring at home, 211-213 curves, 210-211 for diabetes in cats, 201-203, 208, 209-213 in dogs, 197-198, 209-213 with ketoacidosis, 217b monitors for, 212 problems, 211 Blood pH. See also Acid-base disorders acid-base disorders and, 54-61 Blood pressure. See also Hypertension; Hypotension adrenal mass and, XIII:371 in cats, in critical care, XIII:99, XIII:101 indications for measurement of, 714t methods of measurement of, 714-715, 911-912, XIII:835-837 monitoring of with chronic kidney disease, 886-889, 888f, 888t, 910-912, 911f

Blood pressure (Continued ) with nitroprusside, 776, XIII:196 with positive inotropic drugs, 777 with traumatic brain injury, 34 normal and abnormal, XIII:835 screening, 713 substaging of, 888t Blood smear, importance of, XIII:394 Blood transfusion alternatives to, 264-265, XIII:399 canine types for, XIII:396-397 comparison of, to synthetic colloids, XIII:132t donor screening for, XIII:400 for anemia with chronic kidney disease, 917-918 for coagulopathy, 280 for disseminated intravascular coagulation, 290-291, XIII:193 for hereditary coagulopathies, XIII:437 for immune-mediated hemolytic anemia, 269, XIII:431 for noncardiogenic pulmonary edema, XIII:811 for platelet dysfunction, 295-296, 296t for shock therapy, 5, XIII:142-143 for von Willebrand’s disease, XIII:435-436 guidelines for, XIII:400-403 in cats, XIII:102 of platelets (See under Platelet(s)) products for, XIII:402 reactions to, 296, XIII:402-403 substitute for (Oxyglobin), 265, XIII:424-427 typing and crossmatching for, 260-265, XIII:396-399 Blood types canine, 260, XIII:396-397 frequency of, XIII:396t feline, 261-262, XIII:397-398 frequency of, 262t, XIII:398t Blood urea nitrogen (BUN) interpretation of, in kidney failure and hyperthyroidism, XIII:337-338 monitoring of, with uroliths, 933 nonrenal variables affecting, 868-869 with hepatobiliary disease, 546 with urethral obstruction, 951-954 Blood volume, in cats, XIII:99 Blood-typing, 260-265, XIII:396-399, XIII:400401 Blue-green algae toxicity, 150-151 Bluetongue virus, causing pregnancy loss, 987 Body condition scoring (BCS), 192, 193f Body temperature. See Fever; Hyperthermia; Hypothermia Body weight(s), for assessment of hydration, 49 Boldo leaf essential oil, 152t Bone alkaline phosphatase (B-ALP), 545, 549-550 Bone grafts, in open fractures, 85 Bone marrow biopsy for immune-mediated hemolytic anemia, 268 for non-regenerative anemia, 272, 273b for thrombocytopenia, XIII:439 necrosis, 274 neoplasia, 275-275 suppression, from estrogen, 147-148 transplantation, for canine lymphoma, 336-337 Bone transport osteogenesis, 360 Bone tumors from osteosarcoma, 358-362 radiation systems for, XIII:482-485 Bone, effect of early neutering on growth of, 1020 Boots, for physical therapy, 1133 Borage seed oil, as essential fatty acid, XIII:539 Borate(s), for house dust mite control, 427 Borborygmus, 523-727 Bordetella bronchiseptica. See also Tracheobronchitis antimicrobial therapy for, 1226t, 1227-1228 bronchitis diagnosis and treatment of, 646-649 virulence determinants of, 646-647, 647t

  Index Bordetella bronchiseptica (Continued ) nebulization for, XIII:791 rhinitis in cats, 617-618 in dogs, 610, 610b, 613 vaccination, 648-649, 1273, 1273t, 1276t, XIII:250 with chronic bronchitis, 644 Bordetella spp., 646 Boric acid ear therapy, 429, 430t, 431t Borna disease, in cats, XIII:976-978 Borrelia burgdorferi. See Lyme disease Borreliosis. See Lyme disease Bosentan (Tracleer), 701 Botanical insecticide toxicity, 120b, 122-123 Botanical oil extracts, toxicity of, XIII:234 Bougienage, for esophageal stricture, 485 Bovine cross-linked collagen, for urinary ­incontinence, 963, 963f Bowen’s disease, 424, 442 Boxer dog cardiomyopathy in, 728, 796, 797-799 ulcerative colitis of, 521-523, 522f Brachial plexus blockade, for pain management, 15 Brachycephalic upper airway syndrome, ­diagnosis and treatment of, 619-621, 628-629 Brachytherapy, XIII:484 Bradyarrhythmia(s) in cats, 731-739, 734f permanent cardiac pacing for, 717-721 transvenous pacing for, XIII:197-198 Bradycardia arrhythmias and, XIII:719-725 from calcium administration, 244 role in syncope, 709 transvenous pacing for, XIII:197-198 Brain injury, traumatic causing vestibular signs, 1100 diagnosis and treatment of, 33-37, 35t Brain tumors radiation systems for, XIII:482-485 radiotherapy for, 317-318 Brainstem auditory evoked testing, XIII:973 Breath hydrogen testing, XIII:613 Breeding canine pregnancy termination with, 1031-1033 contraception to prevent, 1024-1030 failure of, XIII:925-929 management of, in the bitch, 974-979, 975f, 975t using vaginal cytology and cultures, 980982 progesterone for timing of ovulation, XIII:914-915 using endoscopic transcervical insemination, 983-985 Bretylium tosylate, for defibrillation, XIII:153 Brinzolamide, for feline glaucoma, 1210t, 1211 British anti-Lewisite (BAL), for lead toxicity, 129 Brittany spaniels, C3 deficiency in, XIII:449 Bromethalin toxicity, 118, XIII:212 Bromocriptine mesylate (Parlodel) for canine pregnancy termination, 1032 for false pregnancy, 991 Bronchial collapse, with intraluminal tracheal stents, 636-637 Bronchiectasis, chronic bronchitis and, 644 Bronchitis acute. (See Asthma; Tracheobronchitis) chronic, diagnosis and treatment of canine, 642-645 feline, 650-658 Bronchoalveolar carcinoma, lung, XIII:504t Bronchoconstriction, from asthma, 650-651 Bronchodilators aerosol delivery of, 654-657 for bacterial pneumonia, 662 for chronic bronchitis, XIII:803 and asthma, in cats, 650-658 in dogs, 643-644 for tracheal collapse, 634, XIII:800 Bronchopneumonia. See Pneumonia

1347

Bronchopulmonary disease, pneumonia and, XIII:813 Bronchopulmonary parasites, 667-671, 667f, 668f Bronchoscopy for canine chronic bronchitis, 642 for feline chronic bronchitis or asthma, 653 for interstitial lung disease, 673 for tracheal evaluation, 632-633 and stent placement, 640-641 Brucellosis causing pregnancy loss in the bitch, 986 in the queen, 1044 diagnosis and treatment of, 1234-1236 testicular disease and, in dogs, XIII:944, XIII:944f Brunfelsamidine toxicity, 141 Brunfelsia spp. toxicosis, 140-141 Buchu essential oil, 152t Buckeye tree, 151t Budesonide for chronic colitis, 519, 519t for inflammatory bowel disease, 505 Buffy coat analyzer(s), XIII:395 Bulking agents, for urinary incontinence, 960-964 Bullous emphysema, 688-689, XIII:826-827 Bullous keratopathy, 1199 Bullous pemphigoid, nonsteroidal immunosuppressive therapy for, XIII:536 Bupivacaine for epidural analgesia/anesthesia, XIII:126-127 dosage of, XIII:127t for nerve blocks, 14-16 for pain management, XIII:60 local anesthesia and, in critical care, XIII:124 Buprenorphine (Buprenex) epidural, XIII:127-128 for acute abdomen, 71, XIII:164 for acute pain, dosage guidelines for, XIII:59t for epidural analgesia/anesthesia, dosage of, XIII:127t for feline idiopathic cystitis, 947t for laryngeal paralysis, 628 for neurologic and musculoskeletal pain, 1128t for pain management, 11, 12f-13f, XIII:60 in cats, 478 for tracheal collapse, 633 use of, XIII:123, XIII:125t Bur-otic, 430t Burmese, hypokalemic myopathy in, 1136, XIII:985-987 Buspirone (BuSpar) for feline idiopathic cystitis, 947t for feline lower urinary tract disease, XIII:889t for sensory mutilation, XIII:91 Busulfan, as chemotherapy, XIII:467 Butorphanol (Torbugesic, Torbutrol) adverse reactions of in cats, XIII:241t in dogs, XIII:240t as palliative therapy for cancer, XIII:477 for cough, 634, 645 for feline idiopathic cystitis, 947t for laryngeal paralysis, 628 for neurologic and musculoskeletal pain, 1128t for pain, 11, XIII:60 dosage guidelines, XIII:59t for tracheal collapse, 633 for vomiting cats, 574 in heart failure, 776, 812 use of, XIII:123, XIII:125t Butterfly ingestion, 110-111 C C-reactive protein(s) for pregnancy diagnosis, in dogs, XIII:922 in valvular heart disease, 781 C-sections, epidural anesthesia and analgesia for, 15-16 C3 deficiency, XIII:449t, XIII:519 in Brittany spaniels, XIII:449

1348

  Index

Cabergoline (Dostinex) for canine pregnancy termination, 1032 for false pregnancy, 991 for mastitis, 1000t, 1001 for puerperal tetany, 1000t Cachexia cardiac, XIII:711 nutritional support of cancer, XIII:458-462 (See also EVOLVE) Cadmium, causing nephrotoxicity, 160b Cairn terrier(s), hepatoportal microvascular dysplasia of, XIII:682-686 Calamus essential oil, 152t Calcimimetics, 240 Calcineurin inhibitors, 255-257, 420-421, 421f Calcitonin for hypercalcemia, 346-347, 346f, XIII:347-348 role in calcium homeostasis, 344, 344t Calcitriol (Rocaltrol), 892-895 adverse effects of, 895 dosage of, XIII:344 for chronic kidney disease, 874t, 878, 894-895 for hypoparathyroidism, 243-247, 245t, XIII:344 for progressive renal failure, XIII:862 Calcium. See also Hypercalcemia; Hypocalcemia administration and role in dystocia, 997 concentration in colloid fluids, 63t dietary, role in postpartum eclampsia, 1004-1005 for dystocia, in dogs, XIII:937-938 formula for corrected, 345 homeostasis, 344, 344t monitoring of, with calcitriol therapy, 894-895 overview of metabolism of, with phosphorus, 892-893 supplementation of, for hypocalcemia, 244-246, 244t, 245t, 1002, XIII:341-344 use of, in CPR, 32 Calcium carbonate for hypocalcemia, 245, 245t, XIII:343 for puerperal tetany, 1000t, 1002 Calcium carbonate crystalluria, 851t Calcium channel blocker(s) for feline cardiomyopathy, 811-814, 811t for supraventricular tachyarrhythmias, 725f for systemic hypertension, 715-716 with renal disease, 912, 912t Calcium chloride, 244t, 245t Calcium citrate, 245t Calcium disodium edetate, for toxicity, XIII:207t, XIII:209 Calcium ethylene-diaminetetraacetic acid (Ca EDTA) for lead toxicity, 129 for metal toxicity, 114t Calcium gluconate dosage of, XIII:342-343 for dystocia, 997 for hyperkalemia, 952 for hypocalcemia, 244, 244t, 245t, 952 for puerperal tetany, 1000t, 1001-1002 Calcium ipodate dosage of, XIII:334t for hyperthyroidism, 176t, XIII:337 Calcium lactate, 245t Calcium oxalate crystalluria, 851t, 852, 853f in ethylene glycol toxicity, 132 Calcium oxalate uroliths breeds at risk for, 857t compound, with, XIII:876 dietary therapy for, 237-238, XIII:846 in cats, 935b, XIII:843t in dogs, XIII:846t recurrence of, 935 treatment of, in cats, 931-935, 931f, 932f Calcium phosphate binders, 894 Calcium phosphate crystalluria, 851t Calcium phosphate urolithiasis breeds at risk for, 857t compound with, XIII:876 Calculi. See also Urolithiasis; Specific type e.g. Struvite urolithiasis impact of drugs on formation of, XIII:846-848

Calicivirus, feline control of, in catteries, 1300t, 1301 cutaneous lesions from, 441-442 diagnosis and treatment of, 1284-1287 stomatitis from, 476-478 vaccine recommendations for, 1275, 1276t, 1277 Caloric requirements, 19 during pregnancy and lactation, 1003-1007, 1007f estimating, 194 for diabetic dogs, 207, 207t for gastrostomy tube management, 908 Calorie(s) assessment of, in pet foods, XIII:77-78 in light and lean foods, XIII:78t renal failure and, XIII:862 Camphor oil toxicity, 152-153 Campylobacteriosis causing neonatal diarrhea, XIII:626, XIII:627t causing pregnancy loss, 987 Canaliculus imperforate, XIII:1056 obstructed, XIII:1056 Cancer. See also Neoplasia; specific tumors e.g. Lymphoma drugs and protocols for, 305-314, XIII:474-478 nutritional support with, XIII:458-462 (See also EVOLVE) radiotherapy for, 315-319 Candidatus M. haemominutum, 1245-1246 Candidatus M. turicensis, 1245-1246 Candidiasis, thrombocytopenia from, 283t, XIII:441t Canine adenovirus-1, vaccine ­recommendations for, 1274 Canine adenovirus-2, vaccine ­recommendations for, 1272, 1273t Canine cognitive dysfunction. See Cognitive dysfunction Canine cyclic hematopoiesis, XIII:518 Canine distemper virus. See Distemper Canine granulocytopathy syndrome, XIII:448449 Canine herpesvirus. See under Herpesvirus Canine histiocytic diseases, XIII:588-591 Canine influenza, diagnosis and treatment of, 1291-1294 Canine leukocyte adhesion molecule ­deficiency, XIII:448-449 Canine pattern baldness, XIII:547-548 Canine pigmented, papules and plaques, 444 Canine reactive histiocytoses, 349-350, 1184 Canine sarcoidosis, 464-465 Canine ulcerative colitis, 521-523 Canine(s) DNA testing in, for inherited diseases, XIII:909-913 vaccination recommendations for, XIII:250 Caparsolate, for canine heartworm disease, 839 Capecitabine (Xeloda), post organ ­transplantation, 905 Capillaria aerophila, 670 Capsaicin (Zostrix), for acral lick dermatitis lesions, 472 Carbamate toxicosis, 119-121, 120b, XIII:231-233 Carbapenems, for Enterococci spp. infections, XIII:265 Carbimazole (Neo-mercazole) adverse effects of, XIII:335-336, XIII:335t dosage of, XIII:334t for hyperthyroidism, 176t, 178, XIII:334-336 use of, XIII:334t Carbohydrate(s), for diabetes mellitus management, 200, 205t, 206 Carbon dioxide acid-base disorders and, 56-58 monitoring during CPR, 32 Carbonic anhydrase inhibitor(s) for feline glaucoma, 1210-1211, 1210t for glaucoma, XIII:1078-1079

Carboplatin administration protocol for, XIII:464 as chemotherapy, 310, XIII:470, XIII:474-475 for intracavitary neoplasia, 682-683 for melanoma, 380 for osteosarcoma, 361t Cardiac arrhythmia. See Arrhythmia Cardiac cachexia, nutritional management for, 704-708 Cardiac glycosides, effect of food on, XIII:713 Cardiac neoplasia. See Neoplasia, cardiac Cardiac output, monitoring during shock, 3 Cardiac pacing. See also Pacemaker(s) in critical care, 43-47, 44b Cardiac surgery, indications for, XIII:745-748. See also EVOLVE Cardiac tamponade definition of, XIII:772 from pericardial effusion, 825 Cardiac toxicity doxorubicin causing, 308 lawn care products causing, XIII:222 Cardiac valve replacement, XIII:747-748 Cardiomyopathy. See also Heart failure canine boxer, 797-799 carnitine- and taurine-responsive, in American Cocker spaniels, XIII:761-762 dilated, 792-797 antioxidants for, 708 asymptomatic, 776 cachexia from, XIII:711 carnitine deficiency and, XIII:714 carvedilol for, 775 dietary management for, 707 hypothyroidism and, 186 in boxers, 798 in cardiogenic shock, 776-777 in Doberman pinschers, XIII:757f L-carnitine for, 708 nutritional support of, XIII:711 omega-3 fatty acids for, XIII:715 prognosis for, 793 staging of, 770-774 supraventricular tachyarrhythmias and, XIII:726-730 taurine for, 707-708, XIII:714 ventricular arrhythmias in, 728-729 Doberman pinscher, 800-803, 801f occult, XIII:756-760 pleural effusion and, 675-684 role of supraventricular tachyarrhythmias in, 722 feline, 809-815, XIII:762-767 arrhythmogenic right ventricular, 807-808, 810t-811t, 815-818 arterial thromboembolism from, 811, 811t, 814-818, 820f-821f, 820t, 822f, 822t assessment of, in critical care, XIII:101-102 asymptomatic, treatment of, XIII:763-764 classification of, 809, 815 dilated, 809, XIII:762 diagnosis and treatment of, 810t, 811t, 814 dietary management of, 707 emergency treatment of, XIII:765-766 risk of thromboembolism with, 821f taurine therapy for, XIII:750 hypertrophic, 809, XIII:762 asymptomatic, 810-812 diagnosis and treatment of, 809-813, 810t, 811t risk of thromboembolism with, 819, 821f myocarditis and, 807-808 pleural effusion and, 675-684, 812, 814 restrictive, 809, XIII:762 diagnosis and treatment of, 810t, 811t, 814 emergency treatment of, XIII:764 right ventricular, 815-818 Cardiomyopathy. See also Heart failure therapy of, XIII:751-752 thromboembolism from, diagnosis and treatment of, XIII:766-767 Cardiopulmonary arrest, transvenous pacing and, XIII:198

Cardiopulmonary cerebral resuscitation (CCPR). See Cardiopulmonary resuscitation (CPR) Cardiopulmonary resuscitation (CPR), 28-32 open chest, XIII:147-149 defibrillation and, XIII:152 indications for, XIII:147t Cardiorespiratory disorder(s) associated with obesity, 192b requiring ventilatory support, 603, 607 Cardioversion, 739-743, 741f Cardizem, for feline hypertrophic ­cardiomyopathy, XIII:763, XIII:764 Carelian bear dog(s), and hypopituitary dwarfism, XIII:376 Carminatives, for flatulence, 525-526, 525b Carmustine as chemotherapy, XIII:474 for intracranial tumors, 1081 Carnitine for canine dilated cardiomyopathy, 708, 796 for heart failure, 779t, XIII:750 for hepatic lipidosis, 573 for myopathies, 1116 role in diabetes management, 206, 208 Carnitine deficiency cardiomyopathy from, in American Cocker spaniels, XIII:761-762 role of, in heart disease, XIII:714 Carotid body tumor, 356-357 Carprofen associated liver disease, 568t for anterior uveitis, 1206t for neurologic and musculoskeletal pain, 1128t for ocular diseases, 1151t, 1152 for osteoarthritis, XIII:1019 for pain management, 12f-13f, 14, 14t, XIII:61 Carts, for rehabilitation, 1133 Carvedilol (Coreg) for dilated cardiomyopathy, 775, 796 for Doberman pinscher cardiomyopathy, 802, XIII:758 for heart failure, 772-775, 779t use of, with doxorubicin, 308 Castration early age, 1019-1024 for prostatitis, 1048 Cat scratch disease. See under Bartonellosis Cat(s). See also Feline(s) breathing patterns in, XIII:100t critical care and, XIII:99-104 (See also EVOLVE) microchip implantation site for, XIII:94t rule of 20 for, XIII:99t Cataracts causing blindness, 1165 genetic test for, 1056t with diabetes mellitus, 215 Catecholamine(s). See also specific drug for heart failure, 775 use of, in shock, 6 Caterpillar ingestion, 110-111 Catheter(s) arterial, 39-43, XIII:119 for diagnostic peritoneal lavage, 70 for feline urethral obstruction, 953 for fluid administration, XIII:61-65 for hemodialysis, 897 for parenteral nutrition, 20 for pericardiocentesis, 828, 828f for peritoneal dialysis, XIII:859-860, XIII:859f for pleural effusion drainage, 675-676 for transurethral injection, 963, 963f for urine diversion, XIII:870-871 (See also EVOLVE) for vascular access during CPR, 30 nephrostomy, 933, 934 peritoneal, 72-76 related infections, methods for reducing, 1224 Swan-Ganz, 3 vascular access techniques and care of, 38-43 Catheterization cardiac, for patent ductus arteriosus, XIII:742-744 urethral, 936-937

  Index Cattery(ies) control of viral diseases in, 1299-1305 feline infectious peritonitis in, XIII:292-293 infertility in the, XIII:929 Caulking, 127 Caval syndrome, 839 Cavalier King Charles spaniel dog heart screening of, 772 syringomyelia and Chiari-like malformation in, 1102-1107 valvular heart disease in, 780, 783 xanthine crystalluria in, 854 CD11-CD18 Adhesion protein deficiency, XIII:449t, XIII:451 CDP (Chlorambucil, Dactinomycin, and Prednisone), XIII:471-472 Cefadroxil, adverse reactions of, in cats, XIII:241t Cefazolin for open fractures, XIII:171 for sepsis, XIII:273t minimum inhibitory concentrations (MIC) of, XIII:35t Cefotaxime, minimum inhibitory concentrations (MIC) of, XIII:35t Cefotetan, for sepsis, XIII:273t Cefoxitin for sepsis, XIII:273t minimum inhibitory concentrations (MIC) of, XIII:35t Cefpodoxime proxetil, for pyoderma, 1227 Ceftazidime sodium, for Pseudomonas spp. ear infection, 435t Ceftiofur, minimum inhibitory concentrations (MIC) of, XIII:35t Celinski v. State, 105-106 Celiotomy, XIII:163 alternatives to, XIII:17-21 exploratory, 71 objectives and risks of, XIII:18-20, XIII:20t Cell collection, methods of, 301-302, 302b Cell culture, for feline chlamydiosis, 1186 Cellophane banding, 584-585 Cellular trauma, hyperkalemia and, XIII:375 Cellulose-based solutions, as tear substitutes, XIII:1064t Centipede toxicity, 110 Central venous catheters, 38-43 Central venous pressure (CVP) in noncardiogenic pulmonary edema, 665 monitoring of fluid therapy and, 53 monitoring of, with strokes, 1076-1077 Cephalexin for neutropenia, XIII:269t minimum inhibitory concentrations (MIC) of, XIII:35t Cephalosporin(s), XIII:35t. See also specific drugs causing liver disease, 568t causing nephrotoxicity, 160b for bacterial pneumonia, 661, 661t for lower respiratory tract infections, 1226t, 1228 for sepsis, 1226t, 1227, 1229 for upper respiratory tract infections, 1226t, 1228 for urinary tract infections, 920-921, 920t, 921t, 1226, 1226t in lactating bitch, 1000, 1000t intravitreal, 1148t prophylactic antimicrobial therapy for ­musculoskeletal, 1226t, 1228 subconjunctival, 1147t Cephalothin, minimum inhibitory concentrations (MIC) of, XIII:35t Cerebral blood flow, control of, in traumatic brain injury, 36 Cerebral contusion(s), traumatic brain injury and, 33-37 Cerebral dysfunction, from hypothyroidism, 186 Cerebral edema, from craniocerebral trauma, XIII:178-179 Cerebral metabolic rate, in traumatic brain injury, 36 Cerebral perfusion stroke and, 1077 traumatic brain injury and, 33-34

1349

Cerebral perfusion pressure, and traumatic brain injury, 33-34 Cerebral resuscitation, and CPR, 28-32 Cerebrospinal fluid (CSF) reference values for, with vestibular disease, XIII:970 with central nervous system inflammation, 1070-1071 with vestibular disease, 1100-1101 Cerebrovascular accident, 1074-1077 Cerebrovascular disease, 1074-1077 Ceroid lipofuscinosis, genetic test for, 1056t Cerulytic, 430t Cerumene, 430t Cervical pain from atlantoaxial subluxation, 1084 from cervical spondylomyelopathy, 1088-1093 from syringomyelia and Chiari-like ­malformation, 1102-1107 Cervical spondylomyelopathy, canine, 1088-1093 Cervical vertebral instability-malformation syndromes, XIII:992-1000, XIII:993t, XIII:995t Cesarean section, indications for, in dogs, XIII:938-939 Cetirizine, in cats, XIII:544t Chagas’ disease, myocarditis from, 807 Chalazion, 1179, XIII:1051 Chédiak-Higashi syndrome, XIII:449t, XIII:518-519 in cats, XIII:450 Chelating agents causing nephrotoxicity, 160b for copper, 561-562 for lead ingestion, 129 Chemical poisoning, incidence of, XIII:206t Chemicals causing conjunctivitis, 1177 causing hepatotoxicity, 544b Chemistry(ies). See Laboratory test(s) Chemodectomas, 356-357, 826, 830 Chemoembolization, 970 Chemotherapy. See also specific agent or diagnosis administration of, intracavitary, XIII:478 advanced drug protocols as, 305-311, XIII:465-478 classes of, drugs, XIII:466-471 combination, XIII:465-466 dosing of, 305-314 effects of, on the kidney, 930 for insulinoma, XIII:360 monitoring of, 307-311 multidrug resistance to, XIII:479-482 (See also EVOLVE) practical mechanics of, XIII:462-465 rescue protocols for, XIII:473 timing of, 306 toxicity of, 307-309 with radiotherapy and surgery, 317 Chest tube determining time to pull, 677 for chylothorax, 679 for pneumothorax, 686f, 687f for pyothorax, 676-678 pain management and, XIII:60 suction, 676-677, 687f Cheyletiella spp. differential diagnosis for, in cats, XIII:565t skin scraping for, XIII:526 treatment of, 393-394 Chiari-like malformation, 1102-1107, 1102f-1103f, 1105f-1106f Chinese patent medicines, 123 Chlamydiosis causing conjunctivitis, 1176, 1177, XIII:1044 diagnosis and treatment of, 1185-1187 vaccination recommendations for, XIII:250 Chlorambucil (Leukeran) as chemotherapy, 309, XIII:467 for chronic colitis, 519t, 520 for feline gastrointestinal lymphoma, 341-342 in dermatology, XIII:536-537

1350

  Index

Chloramphenicol for bacterial pneumonia, 661t, 1226t, 1228 minimum inhibitory concentrations (MIC) of, XIII:35t Chlorhexiderm flush, 430t Chlorhexidine dental rinse, 477 shampoos, 414-415, 414t Chloride gap, 56, 56b Chlorinated hydrocarbons, causing ­nephrotoxicity, 160b Chlorine, as disinfectant, XIII:260 Chlorothiazide, and furosemide, for refractory heart failure, XIII:755 Clorox ingestion, 111 Chlorpheniramine maleate for feline pruritus, 408, XIII:543, XIII:544t toxicity of, XIII:229 Chlorpromazine (Thorazine) for parvoviral enteritis, XIII:631, XIII:631t with acute renal failure, 881 Chocolate exposure, 97t toxicity, 110 Cholangiohepatitis. See also Cholangitis feline, XIII:672-674, XIII:673t hepatic fibrosis and, in dogs, XIII:678 with diabetes mellitus, 215 Cholangitis, 576-581 Cholecalciferol toxicity, 160b, 162, XIII:215-216 Cholecystectomy, 588-589 Cholestasis copper accumulation secondary to, 561 sepsis and, XIII:669 ursodeoxycholic acid for, 563-565, XIII:691-693 (See also EVOLVE) Cholesterol. See also Hypercholesterolemia; Hypocholesterolemia concentration in chylothorax, 679 Cholesterol crystalluria, 851t Cholinergic drug(s), for feline glaucoma, 1210t, 1211 Cholinesterase inhibitor toxicity, 114t, 115, XIII:209-210 Cholinesterase inhibitor(s) for autoimmune myasthenia gravis, 1108-1109 insecticides, 119-121, 120b Chondroitin sulfate for feline idiopathic cystitis, 947t, 949 for keratoconjunctivitis sicca, XIII:1063 Chondroprotective compounds, in dogs, XIII:1018-1022 Chondrosarcoma nasal and paranasal, XIII:501t of the trachea and larynx, XIII:503t CHOP (Cyclophosphamide, Doxorubicin, Oncovin, and Prednisone), XIII:471 for canine lymphoma, 336, 337t Chordae tendineae, rupture of, 777f, 780, 785 Chorioretinitis, 1201, 1202f associated with systemic infectious diseases, XIII:277t causing blindness, 1165, XIII:1039 causing mydriasis, 1171 causing retinal detachment, 1216, 1216f Choroid plexus tumors, causing vestibular signs, 1100 Choroid, drug therapy for, 1148 Chow chow(s), growth-hormone responsive dermatosis in, XIII:376 Chromium, XIII:351, XIII:351t causing nephrotoxicity, 160b Chromosomal sex, abnormalities of, 1035, 1036t Chronic lymphocytic leukemia, immunophenotyping for, XIII:508-509 Chronic valvular heart disease. See Valvular heart disease Chylothorax, 678-682, XIII:822-824 Cidofovir, for feline herpesvirus, 1189-1190 Cigarette smoke toxicity. See Tobacco poisoning Cigarette toxicity. See Tobacco poisoning Cilia disorders, XIII:1057 Ciliovitreolenticular block, 1214f

Cimetidine (Tagamet) for acetaminophen toxicity, 113, 114t for feline infectious peritonitis, 1297t for gastrointestinal disorders, due to shock, XIII:144 for kidney failure, XIII:865t interaction of, with cisapride, XIII:616 toxicity of, XIII:229 Ciprofloxacin for leptospirosis, 1239 for neutropenia, XIII:269t for Pseudomonas spp. ear infection, 435t minimum inhibitory concentrations (MIC) of, XIII:35t, XIII:42t Circulation, in CPR, 29-30 Cisapride (Propulsid) for constipation, in cats, XIII:651-652, XIII:651t for esophagitis, 484, XIII:609 for megaesophagus, 491 for urinary retention, 956t for vomiting cats, 574 use of, XIII:615-616, XIII:615t with kidney failure, XIII:865t Cisplatin (Platinol) administration protocol for, XIII:463 as chemotherapy, 310, XIII:469-470 causing nephrotoxicity, 160b effects of, on kidney, 930 for anal sac tumors, 384 for bladder cancer, 372 for intracavitary neoplasia, 682-683 for nasal tumors, 353, 615 for osteosarcoma, 361t toxicity of, in cats, 309 Citrus aurantium toxicity, 151 Citrus oil toxicity, 122, 153 Clarithromycin, for Helicobacter spp. infection, 495-496, 495f Cleaners, toxicity of, XIII:224 Cleaning, disinfectants and antiseptics for, XIII:258-262 CleaRx cleansing, 430t Clemastine fumarate in cats, 408, XIII:544t toxicity of, XIII:229 Client confidentiality, legal considerations for, 108 Clindamycin (Antirobe, Cleocin) adverse reactions of in cats, XIII:241t in dogs, XIII:240t for bacterial pneumonia, 661t, 1226t, 1228 for musculoskeletal infections, 1226t, 1228-1229 for neutropenia, XIII:271 for pyoderma, 1226t, 1227 for pyothorax, 677 for sepsis, XIII:273t for toxoplasmosis, 1256 minimum inhibitory concentrations (MIC) of, XIII:35t prophylactic use of, with dental procedures, 791 Clitoral hypertrophy, 1014-1015, 1015f Clomipramine (Clomicalm) for acral lick dermatitis, 473, XIII:555 for feline idiopathic cystitis, 947t for feline pruritus, 408 for sensory mutilation, XIII:91, XIII:92t Clonality testing, for canine lymphoma, 337-338, 338t Clopidogrel (Plavix) as antiplatelet therapy, 25 for aortic thromboembolism, 814, 824 for prevention of thrombi, 695 Cloprostenol for canine pregnancy termination, 1032 for pyometra, 1009 Chloride, concentration in colloid fluids, 63t Closed-suction drainage, 75, 76t Clostridium spp. causing colitis, 517 causing neonatal diarrhea, XIII:626, XIII:626t in homemade pet foods, 166

CLOtest, 494, 494f Clotrimazole (Veltrim) adverse reactions of, in dogs, XIII:240t cream, toxicity of, XIII:230 for fungal rhinitis, 613-614, XIII:315-317 for Malassezia infections, 456 for otitis, 431t Cloxacillin, for pyoderma, 1226t, 1227 Cluster seizures, 1062, 1063f Co-phenotrope (Lomotil), for cough, 634, XIII:799 Coagulation. See also Disseminated intravascular coagulation; Hemostasis in cats, XIII:102 Coagulopathy and thrombocytopenia, XIII:439 from methimazole, 177 from rodenticide toxicosis, 117-118 hereditary, XIII:434-438 liver disease-associated, 556, 571, 579 COAP (Cyclophosphamide, Oncovin, ­Prednisone and Cytosar), XIII:471 Cobalamin deficiency of in cats, XIII:704 in exocrine pancreatic insufficiency, 533, 541 in hepatic lipidosis, 572 in inflammatory bowel disease, 502-503, 505 malabsorption of, XIII:417t Cobalt 60 units, XIII:482-483 Cocaine toxicity, 145 Coccidia, neonatal diarrhea from, XIII:627t Coccidioidomycosis diagnosis and treatment of, 1265-1267, 1266t, 1267t ocular signs of, XIII:279 of the respiratory tract, XIII:815-819 Cocker spaniel(s), American, cardiomyopathy in, XIII:761-762 Cocoa bean and hull ingestion, 110 Codeine for coughing, 634 toxicity, 145-146 Coenzyme Q10 for canine dilated cardiomyopathy, 708 for feline gingivostomatitis, 478 for myopathies, 1116 Coffee ingestion, 110 Cognitive dysfunction (canine), XIII:53-57 Coin ingestion, 110 Colchicine for amyloidosis, 866 for hepatic fibrosis, XIII:680, XIII:680t for hepatic support, 556 side effects of, XIII:696 Cold therapy for acute pain, 17 for hip dysplasia, 1123 Colectomy, for megacolon, XIII:652 Colitis canine ulcerative, 521-523 causes of, XIII:644t chronic, 515-520, XIII:643-648 nutritional management of, XIII:657-658 Collie eye anomaly, genetic test for, 1056t Collie(s) avermectin toxicosis in, 125-127, 390-392, 668 grey, cyclic hematopoiesis in, XIII:450 Collagen injections, for urinary incontinence, 963-964, 970 Colloid oncotic pressure, XIII:116-118 in cats, in critical care, XIII:99-100 Colloid osmometry, XIII:116-118. See also EVOLVE Colloid(s) characteristics of, 63t choices, 65t fluid therapy, 50-54, 61-67 for disseminated intravascular coagulation (DIC), 290 for gastric dilatation-volvulus, 78-79, 78t, 81 for noncardiogenic pulmonary edema, 664 for sepsis, XIII:273 for shock therapy, 5, 51, XIII:141-142

Colloid(s) (Continued ) for traumatic brain injury, 35, XIII:181t pharmacology of, 62-63, XIII:132 recommendations for, XIII:131-136 solutions, XIII:67t use of, XIII:66-69 Colloidal oatmeal shampoo, 411-412, 411t Colonic impaction, feline, XIII:648-652 Colonoscopy, 517-518, XIII:646 Colony-stimulating factors. See Granulocyte colony-stimulating factor Colostrum, failure to receive, causing ­immunodeficiency, XIII:519 Commit ingestion, 136 Common bile duct patency, 588 Complete blood count. See Hematology Compounding methimazole, 177-178 Computed tomography (CT) comparison of, to echocardiography, XIII:709 for atlantoaxial subluxation, 1085 for cardiopulmonary disease, XIII:709-710 (See also EVOLVE) for encephalitis and meningitis, 1071 for feline urinary calculi, 933 for ocular neoplasia, 1154, 1154f for stroke, 1075 for vestibular disease, 1101 of adrenal mass, XIII:370 of pituitary gland, XIII:367 to evaluate for metastasis, 362 to evaluate pericardial effusion, 829 to evaluate pulmonary thromboembolism, 692 to evaluate rhinitis, 352, 609-616, 611f, 617 with craniocerebral trauma, XIII:180 Computer(s), for searching veterinary literature, XIII:2-8 Conception, failure of, XIII:925-929 Concussion, and traumatic brain injury, 33 Congenital disease(s). See also Inherited disorders brachycephalic upper airway syndrome, 619-621 breeds associated with deafness, XIII:972-973 cardiac catheterization for, XIII:742-744 causing diarrhea, XIII:625 cervical vertebral instability, XIII:992-1000 Doberman pinscher cardiomyopathy, 800-803, 801f endocarditis and, XIII:768 hepatoportal microvascular dysplasia as, XIII:683-684 in cats, XIII:738-741, XIII:739t-740t (See also EVOLVE) mitral valve dysplasia, 765-768 myotonia, in cats, XIII:987-989 neutrophil dysfunction, XIII:448-450 optic nerve abnormalities, XIII:1040 patent ductus arteriosus, 744-747 portosystemic shunts, 581-586 prophylactic antibiotics with, 791 pulmonic stenosis, 752-756 reproductive tract and, XIII:904-909 (See also specific disorders) screening for boxer cardiomyopathy, 798 subaortic stenosis, 757-761 tests available for hereditary diseases, 1055t, 1056t, 1057t tricuspid valve dysplasia, 762-765 vaginal anomalies in the bitch, 1012-1018 ventricular septal defect, 748-751 Congestive heart failure. See Cardiomyopathy; Heart failure Conium maculatum, 151t Conjunctiva hyperemia of, 1176-1177 neoplasia of, 1155-1156, 1155f Conjunctival grafts, XIII:1073 Conjunctivitis, XIII:1043 associated with systemic infectious diseases, XIII:276, XIII:277t canine, XIII:1053-1054, XIII:1053t, XIII:1054t (See also EVOLVE)

  Index Conjunctivitis (Continued ) feline from chlamydiosis, 1185-1187 from herpesvirus-1, XIII:1059-1060 from mycoplasma, XIII:1059-1060 red eye from, 1175-1177, 1176f Conn’s syndrome, 1136 Consciousness, declining, in cats, XIII:101 Constant-rate infusion (CRI) diazepam, 1063f dobutamine, 796, 813 esmolol, 818 fentanyl, 88-89, 823 FLK, 16t for mechanical ventilator support, 607 for pain management, 12f-13f furosemide for acute heart failure, 776 for noncardiogenic pulmonary edema, 665 for oliguria and anuria, 880-881, 880t intravenous pain drugs, 88-89 lidocaine, 729, 818 metoclopramide, 881 MLK, 16t nitroprusside for noncardiogenic pulmonary edema, 665 potassium bromide, 1064 propofol, 1063f pyridostigmine bromide, 1110 Constipation feline, XIII:648-652, XIII:651t (See also EVOLVE) from uremia, XIII:865 Construction product poisoning, incidence of, XIII:206t Continuous positive airway pressure ­ventilation, 601 Continuous-rate infusion. See Constant-rate infusion Contraception, for the bitch, 1024-1030 Contraceptive product ingestion, 148-149 Contrast radiography. See Radiography Convallaria majalis, 151t Cooling procedures for laryngeal paralysis, 628 for tracheal collapse, 633 Coombs’ test for autoimmune hemolytic anemia, 268, XIII:429-430 for systemic lupus erythematosus, XIII:515 Coonhound paralysis, 1115 COP (Cyclophosphamide, Oncovin and ­Prednisone) protocol, XIII:471 for feline gastrointestinal lymphoma, 342, 342t COPLA (Cyclophosphamide, Oncovin, Prednisone, L-asparaginase, Adriamycin), XIII:472 Copper metabolism, 557, 558f, 558t Copper toxicosis, 114t, 115 autosomal recessive inheritance of, XIII:910t genetic test for, 1056t treatment of, XIII:209 Copper-associated chronic hepatitis, 557-562, XIII:695 Cor pulmonale, from canine heartworm ­disease, 838-839 Coring technique, 302 Cornea, Also See Keratitis colors as diagnostic aid of, 1158-1163, 1163t degeneration of, XIII:1069 dystrophy of, XIII:1068-1069 edema of, 1159-1160, 1159f, 1160f associated with systemic infectious ­diseases, XIII:277t evaluation of, with blindness, XIII:1038 foreign bodies of, XIII:1091-1092 lipid dystrophy of, 1160-1161, 1161f nonulcerative diseases of, XIII:1067-1071 (See also EVOLVE) opacity of, causing blindness, 1164-1165 pigmentation of, 1161, 1161f, 1162f scars of, 1160, 1160f sequestrum of, 1161, 1162f, XIII:1070 ulceration of, XIII:1071-1075, XIII:1072t, XIII:1091 (See also EVOLVE; keratitis) vascularization of, 1158-1159, 1159f, 1175

1351

Corneal lipidosis, associated with hypothyroidism, XIII:328 Corneal stroma, drug therapy for, 1146-1148 Corneal ulceration, 1177 corneal edema from, 1160f fluorescein dye testing for, 1144 nonhealing, in dogs, 1197-1200 steroid use in, 1150 vascularization from, 1158, 1159f Corneoscleral transposition surgery, XIII:1073 Coronary artery disease, XIII:730-731 Coronavirus antibody titers to, XIII:291-292 neonatal diarrhea from, XIII:627t outcomes of, with FIP, 1295, 1296f Coronavirus 3C-like protease inhibitors, for feline infectious peritonitis, 1297t Corrosives, toxicity of, XIII:225 Corticosteroid alkaline phosphatase (C-ALP), 545, 549-550 Corticosteroid(s). See Cortisol; Glucocorticoid(s) Corticotropin-releasing hormone (CRH), role of, in hyperadrenocorticism, XIII:364 Cortisol, 401. See also Glucocorticoid(s); Hydrocortisone; Hyperadrenocorticism; Hypoadrenocorticism effect of on ACTH stimulation test, XIII:321 on nonadrenal disease, XIII:362-363 in-house assay (SNAP) of, 232 role of in health and disease, 228-230 in hyperadrenocorticism, 219, 221-223, 222t Cortrosyn (ACTH gel), 170, 231-232 Cosequin, for osteoarthritis, XIII:1021 Cough causing syncope, 710 from asthma, in cats, 650-658 from chronic bronchitis in cats, 650-658 in dogs, 642-645 from heart failure, 773, 781, 785 from heartworm disease, 833 from pleural effusion, 675-684 from tracheal collapse, 631-632, 631f, 638f compared to heart failure, XIII:798 management of, XIII:799-800 medical management of, 634 Coumadin. See Warfarin Coupage, 662, XIII:791-792 Cowpox virus, 442-443 COX inhibitors. See Cyclooxygenase (COX) inhibitors Coxiella burnetii, causing pregnancy loss in the queen, 1044 Coxofemoral joint disease, 1120-1125, 1124t Crack toxicity, 145 Cranial nerve blockade, for pain management, 15 Craniectomy, decompressive, 37 Craniocerebral trauma. See Head trauma Creatinine abnormalities in, differential diagnosis of elevated, XIII:108t clearance tests, 869-870 in abdominal fluid, 71 interpretation of, in kidney failure and hyperthyroidism, XIII:337-338 monitoring of, with uroliths, 933 nonrenal variables affecting, 869 relationship to glomerular filtration rate, 869 staging of, with chronic kidney disease, 886t toenail concentrations of, XIII:858 with urethral obstruction, 951 Creatinine clearance, XIII:16 Crenosoma vulpis, 669-670 Cricopharyngeal achalasia, 479 Critical care. See also Emergency acid-base disorders in, 54-61 acute renal failure in, XIII:173-178 anesthesia for, procedures of, XIII:122-126 bacterial translocation in, XIII:201-203 (See also EVOLVE)

1352

  Index

Critical care (Continued ) cardiac pacing in, 43-47 cats in, differences of, XIII:99-104 (See also EVOLVE) colloid osmometry in, XIII:116-118 (See also EVOLVE) colloid use in, XIII:131-136 dietary requirements in, in cats, XIII:104-105 disseminated intravascular coagulation (DIC) in, XIII:190-194 epidural use, in, XIII:126-131 (See also EVOLVE) microenteral nutrition for, patients, XIII:136-140 (See also EVOLVE) neutropenia and, XIII:267-272 nutrition in, 18-23 oxygen therapy for, 596-603 point-of-care laboratory testing in, XIII:110-112 (See also EVOLVE) sepsis in, therapy of, XIII:271-275 shock in, therapy of, XIII:140-147 transvenous pacing in, XIII:197-200 vascular access in, 38-43 ventilator therapy in, 603-609 Crossmatching blood, 263-265 Crotalus atrox toxoid, vaccination for, 1274 Cryoprecipitate for coagulopathies, 280, XIII:437 for von Willebrand’s disease, 278-279 transfusion of, XIII:402 Cryotherapy for acral lick dermatitis, 471 for papillomaviruses, XIII:570 Cryptococcosis causing anterior uveitis, 1203b, 1204 central nervous system, 1072-1073 diagnosis and treatment of, 1265-1267, 1266t, 1267t nasal, 613-614 nasopharyngeal, 624-625 ocular signs of, XIII:278 of the respiratory tract, XIII:815-819, XIII:817f Cryptorchidism, 1039, XIII:908, XIII:945-946, XIII:946f Cryptosporidiosis, ELISA for diagnosis of, XIII:11 Crystalloid(s) composition of, solutions, XIII:82t for fluid therapy, 50-54 for shock therapy, 4-5, 51, XIII:141 use of, with colloids, 66 Crystalluria drug-associated, XIII:846-848 interpreting and managing, 850-854 CT. See Computed tomography (CT) Cullen’s sign, 69b Culture(s). See also under Laboratory test(s) bacterial antimicrobial therapy and, XIII:34-35 endocarditis and, XIII:768-769 for small intestinal overgrowth, XIII:639 blood (See Blood culture(s)) empiric antimicrobial therapy while waiting for, 1225-1229, 1226t fecal tritrichomonas, 510 for cause of bacterial pneumonia, 660-661 for Pythium spp. infections, XIII:314 for surveillance of hospital-acquired ­infections, 1223 fungal, 457-458 mastitis, 1001 nasal in cats, 617 in dogs, 610, 612-613 of lagenidium spp., 1279 of pythiosis, 1269 prostatic, 1047-1048 resistant infections and, XIII:262-263 tracheobronchial, in cats, 653, 655-656 urine for feline lower urinary tract disease (FLUTD), 946t interpretation of, 919 vaginal, 980-982, 1043 with pyometra, 1009

Curare, XIII:208t Curschmann’s spirals, 643 Curved forceps technique, for esophageal ­feeding tube placement, 591-592, 591f, 592f Cushing’s disease. See Hyperadrenocorticism Cushing’s reflex, and traumatic brain injury, 34 Cutaneous. See under Skin; specific disorders Cutaneous exophytic papilloma, 444 Cutaneous inverted papilloma, 444 Cutaneous xanthoma, 462-463 Cutdown, technique for vascular access, 38-43, 40f, 41f Cuterebra spp. larvae, nasopharyngeal, 624, 667 CVP. See Central venous pressure Cyanide toxicity, from sodium nitroprusside, XIII:195 Cyanoacrylate, opthalmic, XIII:1073 Cyanuric acid, causing nephrotoxicity, 165 Cyclic hematopoiesis, XIII:417t, XIII:418, XIII:450, XIII:454 Cyclic neutropenia, XIII:449t Cyclizine, toxicity of, XIII:229 Cyclooxygenase (COX) inhibitors. See also specific drug for neurologic and musculoskeletal pain, 1128t, 1129-1130, 1129f in patients with heart failure, 779 role of, in gastric ulceration, 498-500, 499f Cyclooxygenase-2 (COX-2) in bladder tumors, 371-372 in nasal tumors, 626 Cyclophosphamide (Cytoxan), XIII:510 administration protocol for, XIII:464 as chemotherapy, 309, XIII:466-467 as immunosuppressive agent, 254 for autoimmune myasthenia gravis, 1109-1110 for canine lymphoma, 336, 337t for feline gastrointestinal lymphoma, 341-342, 342t for hemangiosarcoma, 330 for immune-mediated hemolytic anemia, 270, XIII:432 for mammary cancer, 365 for osteosarcoma, 362 for thrombocytopenia, XIII:440 Cycloplegic drugs, 1206, 1206t Cyclosporine adverse reactions to, 387-388, 409 as immunosuppressive agent, 255-256, XIII:510-512 associated liver disease, 568t causing nephrotoxicity, 160b for autoimmune myasthenia gravis, 1110 for chronic colitis, 519t, 520 for episcleritis, in dogs, 1191t, 1192 for feline asthma, XIII:809 for feline caudal stomatitis, 478 for feline pruritus, 409 for histiocytic diseases, 350 for immune-mediated hemolytic anemia, 270, XIII:432 for inflammatory bowel disease, 505 for keratoconjunctivitis sicca, XIII:1062 for ocular diseases, 1152, 1152t for perianal fistulas, 468, 529 for sebaceous adenitis, 452 for skin diseases, 386-388, 387t, 409 for tear film disturbances, 1196 for thrombocytopenia, 286t formulations of, 255-256, 386, 409 in dermatology, XIII:537 monitoring of, 388, 409, 529 post organ transplantation, 904-905 role of, in toxoplasmosis, 1255 topical, 421 use of, with prednisolone, 255-256 Cyproheptadine adverse effects of, 656 as appetite stimulant, 308, XIII:461 as palliative therapy for cancer, XIII:478 for feline asthma, 656, XIII:809 for serotonin syndrome toxicity, 114t, 115 in cats, XIII:544t

Cyst, laryngeal, 629 Cystadenocarcinoma, renal, 928 Cystic endometrial hyperplasia (CEH), causing pregnancy loss, 988 Cystic orbital disease, XIII:1088 Cystine crystalluria, 851, 851t, 852-853, 853f Cystine urolithiasis breeds at risk for, 857t dietary recommendations for, XIII:846 in cats, XIII:843t in dogs, XIII:846t Cystitis. See also Feline lower urinary tract disease; Feline lower urinary tract disease (FLUTD) idiopathic feline, XIII:894-895 management of obstructed, 951-954 management of unobstructed, 944-950 Cystometrogram (CMG), 961 Cystoscopy for bacterial urinary tract infections, in cats, XIII:882 for bladder cancer, 371 for bladder polyps, 970 for injectable bulking agents, 962, 962f for interstitial cystitis, XIII:895 for ureter evaluation, 971f for urethral stenting, 966-967 stone removal, 939 Cystostomy tube(s), 968 for urine diversion, XIII:870-871 (See also EVOLVE) Cystotomy, for feline lower urinary tract ­disease (FLUTD), 946t Cystourethrogram, 969f, 970 Cysts, nasopharyngeal, 626 Cytauxzoonosis diagnosis and treatment of, 1261-1264, 1261f, 1262f thrombocytopenia from, 283t, XIII:440, XIII:441t vector associated with, XIII:296t Cytisus scoparius, 151t Cytochrome-b5 reductase (Cb5R) deficiency, XIII:416t Cytograms, interpretation of, XIII:381-390 Cytokine inhibitors as immunosuppressive agents, 257-258 for myocarditis, 806 Cytokine(s), gene therapy and, XIII:494-495 Cytologic immunostaining, XIII:454 Cytology acute abdomen and, XIII:163 collection of specimens for, 301-304, 302b, 303f ear, 428-429 eye, 1144 for bacterial pneumonia, 661 for chronic bronchitis, 643, XIII:802 for dermatology and Malassezia, XIII:574-575 interpretation of, XIII:528-529 techniques of, XIII:528-529 for Helicobacter spp., 493-494, 494f for hepatobiliary disease, XIII:662 for lagenidiosis, 1270-1271 for Malassezia infections, 454-455 for pleural effusion, 675-677 nasal, 611 nasopharyngeal, 623 of aqueous humor, 1202 of body cavity fluids, XIII:1224t of chylothorax, 679 of mast cell tumors, 374 of pythiosis, 1268-1269 rectal, 517 tracheobronchial, in cats, 653 vaginal, 977-978, 980-982 during false pregnancy, 990 for feline ovarian remnant syndrome, 1040 for infertility, in cats, XIII:929 with pregnancy loss in queens, 1042-1043 with pericardial effusion, 825-826

Cytoplasmic antigen agar gel immunodiffusion test, for brucella canis, 987 Cytosine arabinoside (Cytosar) as chemotherapy, XIII:468 for intracranial tumors, 1079t, 1081-1082 Cytotoxic drugs for cancer, 305-314, 312t for immune-mediated hemolytic anemia, 270 D D-dimers, in pulmonary thromboembolism, 691 D-Penicillamine for hepatic fibrosis, XIII:680-681, XIII:680t for metal toxicity, XIII:207t, XIII:209 Dacarbazine (dimethyltriazenoimidazole carboxamide [DTIC]), as chemotherapy, XIII:470 Dachshund dog, heart screening of, 772 Dacryocystitis, diagnosis and treatment of, XIII:1056 Dalmatian dog inherited copper hepatitis, 561 urate crystalluria in, 851, 853-854 Dalteparin (Fragmin) as anticoagulant therapy, 26-27 for arterial thromboembolism, 824 for prevention of thrombi, 694 Danazol (Danocrine) for immune-mediated hemolytic anemia, XIII:432 for thrombocytopenia, XIII:440-441 Dantrolene for feline lower urinary tract disease, XIII:889t, XIII:891 for urinary retention, 956t Darbepoetin (Aranesp), for chronic kidney disease, 874t, 877, 917 Datura stramonium, 151t DDD pacing systems, 718t, 719-721 Deafness, XIII:971-974 Debridement, of degloving or shearing wounds, XIII:1033 Decision-making, using evidence-based ­medicine, XIII:2-8 Decontamination, for toxicities, 96-99, 97f, 97t, 112-116 Decoquinate, for hepatozoonosis, XIII:311, XIII:312t Decortication, for chylothorax, 680-681 DEET mosquito repellent, 111 Deferoxamine for craniocerebral trauma, XIII:184 for gastric dilatation-volvulus, XIII:167 for iron toxicity, XIII:207t, XIII:209 for metal toxicity, 114t, 115 Defibrillation, XIII:150-153 electrical, during CPR, 30 variables affecting, XIII:151t Degenerative myelopathy, rehabilitation considerations for, 1135, 1135b Degloving wounds, XIII:1032-1035 Degreaser toxicity, 134 Dehydration. See also Fluid therapy fluid therapy for, 48-54, 52t physical finding with, 49 Dehydroepiandrosterone, for feline infectious peritonitis, 1297t Deicer, 132 Demecarium bromide, for feline glaucoma, 1210t, 1211 Demodex cati, 439-440 Demodex gatoi, 438-439 Demodicosis causing blepharitis, 1179-1180 feline, XIII:581t diagnosis and treatment of, 438-440, XIII:580-582 differential diagnosis for, XIII:565t interleukin(s) and, XIII:411 neutrophil dysfunction in, XIII:449t treatment of, 394 trichography for diagnosis of, XIII:527 Denatonium benzoate, 130 Dendritic antigen-presenting cells, 348

  Index Dental disease, of cats, 476-478, 477-478 Deoxycorticosterone pivalate (DOCP), for hypoadrenocorticism, 234 Deoxyribonucleic (DNA) acid-based tests, for dogs, 1054-1055 Depot deslorelin, for urinary incontinence, 957t Depot leuprolide, for urinary incontinence, 957t Deracoxib (Dermaxx) for anterior uveitis, 1206t for neurologic and musculoskeletal pain, 1128t for ocular diseases, 1151t, 1152 Dermatitis. See also Acral lick dermatitis; Allergy(ies); Atopy; Dermatosis; Pruritus; Pyoderma; Pyotraumatic dermatitis (hot spots); Skin; specific conditions acral lick, 468-473 cyclosporine for, 386-388 feline herpes ulcerative, 1180 from hypothyroidism, 185 from methimazole, 175 juvenile cellulitis (puppy strangles), 1183-1184 Malassezia (See underMalassezia) nonneoplastic nodular histiocytic diseases, 462-465, 462b of the eyelids, 1178-1184 perivulvar, 1013-1014, 1014f solar-induced, nasal, XIII:500 superficial necrolytic, 1181 Dermatofibrosis, with renal ­cystadenocarcinoma, 928 Dermatologic disorder(s) acral lick dermatitis, 468-473 allergen-specific immunotherapy for, 415-420 anal sac diseases, 465-468 associated with obesity, 192b avermectins for, 390-394 cyclosporine for, 386-388 cytology for, XIII:528-529 dermatophytosis, 457-461 essential fatty acids for, XIII:538-542 examination of scales with, XIII:527 eyelid and periocular skin diseases, 1178-1184 feline demodicosis, 438-440 feline viral, 441-443 formulas of solutions for, XIII:527t from pythiosis, 1268 fungal culture for, XIII:529-530 glucocorticoids for, 400-405 house dust mites causing, 425-427 hyperbaric oxygen for wounds, 600-601 hypoallergenic diets for, 395-397, XIII:530-536, XIII:533t (See also EVOLVE) interferons for, 389-390 laboratory tests for, XIII:526-530, XIII:527t leishmaniasis causing, 1253 Malassezia infections, 453-457, 455t materials needed for, procedures for, XIII:526t methicillin-resistant canine pyoderma, 449-450 nonneoplastic nodular histiocytic diseases, 462-465 otitis, 428-437 papillomaviruses, 443-446 pentoxifylline for, 397-400 pyotraumatic dermatitis (hot spots), 446-449 sebaceous adenitis, 451-453 shampoo therapy for, 410-415, 411t, 412t, 414t topical immune modulators for, 420-425 Wood’s lamp examination for, XIII:529 Dermatomycosis. See Dermatophytosis Dermatomyositis, 398, 1113 Dermatophagoides farinae, 425 Dermatophyte test medium (DTM), 457-458 Dermatophytosis, XIII:577-580 Dermatophytosis causing blepharitis, 1179 differential diagnosis for, in cats, XIII:565t fungal culture for, XIII:529-530 shampoo therapy for, 414t, 415 treatment of, 457-461, 458b, 459t Wood’s lamp examination for, XIII:529

1353

Dermatosis. See also under Dermatitis drug eruptions and, XIII:556-559 essential fatty acids for, XIII:538-542 eyelid, XIII:1052 growth-hormone responsive, XIII:376-377 (See also EVOLVE) Dermoids, ocular, 1155 Desmopressin acetate (DDAVP) after water deprivation testing, XIII:834 for diabetes insipidus, XIII:325-326 (See also EVOLVE) for platelet dysfunction, 296, XIII:446 for testing causes of polyuria and polydipsia, 847-848 for von Willebrand’s disease, XIII:436 formulations of, XIII:325 Detemir, in cats, 201 Detergents, toxicity of, XIII:223-224 Deworming. See Parasite(s) Dexamethasone causing gastric ulceration, 498-499 comparison of, to other glucocorticoids, 401t definition of, 401 effect of, on ACTH testing, 232 for anterior uveitis, 1205, 1206t for canine pregnancy termination, 1032-1033 for episcleritis, in dogs, 1191t, 1192 for feline infectious peritonitis, 1296b for feline pruritus, 407-408 for laryngeal paralysis, 628 for neurologic and musculoskeletal pain, 1128t for ocular diseases, 1150, 1150t for spinal cord disease, XIII:188 for tracheal collapse, 633 subconjunctival, 1147t topical otic, 432t use of, with infectious diseases, 1232-1233, 1232t, 1233t Dexamethasone suppression test drug choice for, 171 effect of, on ACTH testing, 171 interpretation of, 171, XIII:321-322 Dexmedetomidine, for pain management, 13, 13t Dexrazoxane, XIII:477 Dextran 70, 64-65, 65t, XIII:67t characteristics of, 63t use of, in gastric dilatation-volvulus, 78 Dextran(s) colloid therapy using, XIII:66-67 disseminated intravascular coagulation and, XIII:193 for therapy of shock, XIII:142 use of, XIII:133-134, XIII:133t Dextrose 20%, for oliguria and anuria, 880t 50%, for reduction of vaginal prolapse, 1018 concentration of, in colloid fluids, 63t for hyperkalemia, 233-234 Diabetes insipidus, 845-845 causes of secondary nephrogenic, 845-846, 846t central, 845, XIII:326 diagnosis and treatment of, with desmopressin, XIII:325-326 (See also EVOLVE) Diabetes mellitus. See also under Insulin canine concurrent hypothyroidism with, XIII:329-330 diagnosis and treatment of, 195-199 dietary therapy for, 196, 204-209, 205t effect of metoclopramide on, XIII:615 on adrenal function tests, XIII:362-363 on liver, XIII:668t, XIII:670-19-19 on thyroid function, 187 complications from, 214, XIII:354-357 feline diagnosis and treatment of, 199-204, 202b dietary therapy for, 204-209, 208t Heinz body formation in, XIII:422

1354

  Index

Diabetes mellitus (Continued ) feline (Continued ) monitoring of, 203, 209-213, 714t non-insulin dependent, XIII:350-354, XIII:351f (See also EVOLVE) remission of, 200 food type and feeding plan for, 207, 207t glucose curve for, 197-203, XIII:349-350 hypertension and, 713, 714t monitoring of, 198, 209-213, XIII:348-350 neuropathy from, 1115 neutrophil dysfunction in, XIII:449t nonketotic hyperosmolar, 218 polyuria and polydipsia from, 846t poor response to, XIII:356t risk of pulmonary thromboembolism with, 696 Somogyi effect in, XIII:355 transient, XIII:354-355 urinary tract infection associated with, XIII:878-880 with oral hypoglycemics, XIII:353 Diabetic ketoacidosis (DKA), 216-218, 217b Diabetic nephropathy, 214 Diabetic neuropathy, 214-215 Diagnostic imaging, for diagnosis of acute abdomen, 70 Diagnostic molecular techniques, XIII:455-456 Diagnostic peritoneal lavage, for diagnosis of acute abdomen, 70-71 Diagnostic test(s). See also Laboratory test(s); specific disorder accuracy of, in assessing veterinary literature, XIII:4-8 acute abdomen and, XIII:162 for adrenal disease, 170-172 for pericardial effusion, XIII:773-775 for thyroid disease, 172-173 strategies for neoplasia, XIII:452-458 thoracoscopy as, XIII:157-159 (See also EVOLVE) Dialysate solutions, XIII:860 Dialysis. See Hemodialysis; Peritoneal dialysis Diaphragmatic hernia, 87 epidural anesthesia and analgesia for, 15-16 Diaphragmitis, 807 Diarrhea chronic colitis causing, 515-520 chronic, idiopathic in young cats, XIII:627-628 diagnostic approach to chronic, 508-509, 508f diets (recipes) for, XIII:658t fiber for, dietary sources of, XIII:658t large intestinal See (Colitis) neonatal, diagnosis and treatment of, XIII:625-628 nutritional management of, XIII:653-658 responsive to tylosin, 506-509 small intestinal, treatment of, XIII:653-654 Diatrizoate meglumine (Gastrografin), for hyperthyroidism, 179 Diazepam (Valium) adverse reactions to, XIII:687 in cats, XIII:241t as appetite stimulant, XIII:461 associated liver disease, 568t constant rate infusion of, 1063f for appetite stimulation, 575 for feline lower urinary tract disease, XIII:889t, XIII:891 for metronidazole toxicity, 114t, 115 for seizures, XIII:961t, XIII:962 from intracranial tumors, 1079t, 1082 for status epilepticus, 1063f, 1064 for strychnine toxicosis, 118 for urinary retention, 955, 956t in traumatic brain injuries, 35t side effects of, XIII:122 use of, XIII:122-123, XIII:125t in cats, XIII:964-965 Diazoxide (Proglycem), for insulinoma, XIII:360 DIC. See Disseminated intravascular coagulation

Dichlorophen, adverse reactions to in cats, XIII:241t in dogs, XIII:240t Dichlorphenamide for feline glaucoma, 1210-1211, 1210t for glaucoma, XIII:1093 Diclofenac for anterior uveitis, 1205, 1206t for ocular diseases, 1151t, 1152 Dicloxacillin, for pyoderma, 1226t, 1227 Dicyclomine for urinary incontinence, 957t for urinary tract disease, XIII:900t, XIII:901 Didanosine, for feline retrovirus, 1281t Diesel toxicity, 134 Diet(s) modification of, conditions for, XIII:632t related diarrhea, in neonates, XIII:625-626, XIII:627t Dietary sensitivity, XIII:632-637. See also EVOLVE Dietary supplement(s) and herbal hazards, 149-150 for heart diseases, 704-708 Dietary therapy. See also Anorexia; Nutrition effect of, on urine specific gravity, 868 for calcium oxylate uroliths, in cats, 935, 935b for cancer patients, XIII:460-461 for canine diabetes mellitus, 196, 204-209, 205t for chronic bronchitis, 645 for chronic kidney disease, 873t, 874-875, 891, 893, 916 gastrostomy tube feeding for, 906-910 nutritional assessment of, 906-907 for chylothorax, 679 for colitis, 517-518 for copper-associated hepatitis, 562 for diarrhea, XIII:653-658 for exocrine pancreatic insufficiency, 533, 541 for feline diabetes mellitus, 201 for feline idiopathic cystitis, 949 for feline inflammatory liver disease, 578-579 for feline lower urinary tract disease, 945b, 949 for flatulence, 525-526, 525b for food allergies, 395-397, 396t for heart disease, 704-708, 773, 779t, 784, 796 for heart failure, XIII:749-750 monitoring of, XIII:715-716 refractory, XIII:754 for hepatic encephalopathy, 569, 571 for hepatic lipidosis, 572-574 for hip dysplasia, 1122-1123 for hypercalcemia, 237-238 for hypertension, XIII:839 for inflammatory bowel disease, 503-505 for interstitial cystitis, XIII:895 for obesity, 193-194 for pancreatitis, 536 for portosystemic shunts, 584, 585f, 586 for pregnancy, in dogs, XIII:931 for protein-losing enteropathy, 514 for the pregnant and lactating bitch, 204-209, 208t, 1003-1007 for tracheal collapse, 633 for urinary diseases, XIII:841-846, XIII:842t-843t, XIII:844t-845t low-sodium treats, 705t progressive, XIII:861-862 sodium-restricted, 704-708 with megaesophagus, 491 with peritoneal dialysis, XIII:860 Diethylcarbamazine adverse reactions of, in dogs, XIII:240t for feline leukemia virus, XIII:284 for feline retrovirus, 1281t for heartworm prevention, in dogs, XIII:780 Diethylcarbamazine-oxibendazole, toxicity of, XIII:218 Diethylene glycol toxicosis, XIII:212 diagnosis and treatment of, 132-133, 160-162 from paintball ingestion, 141-142

Diethylstilbestrol (DES) associated liver disease, 568t for benign prostatic hypertrophy, 1047 for urinary incontinence, 957t, 958 for vaginitis, 1011 toxicity, 147-148 Diff-Quick stain, for cytology, 304, 454 Difloxacin minimum inhibitory concentrations (MIC) for, XIII:42t tissue concentrations of, XIII:45t Diflunisal, toxicity of, XIII:227 Digestive tract. See under Gastric; Gastrointestinal Digital papillomatosis, 444 Digitoxin, effect of food on, XIII:713 Digoxin dosing of, with obesity, XIII:713 drug monitoring of, XIII:28t effect of food on, XIII:713 for atrial fibrillation, with heart failure, 775, 777, 795 for dilated cardiomyopathy, in dogs, 795 for feline cardiomyopathy, 811t, 814, 818 for feline myocardial failure, XIII:765 for heart failure, 772-775, 779t, 784, XIII:750-751 for supraventricular tachyarrhythmias, 725f, 726, XIII:729 for syncope, 712t interaction of, with cisapride, XIII:616 monitoring therapy of, 784, 795, XIII:750-751 toxicity of, XIII:751 metabolic diseases associated with, XIII:713 Digoxin fab fragments (Digibind), 154t Dihydrotachysterol, for hypoparathyroidism, 245, XIII:344 Dilated cardiomyopathy. See Cardiomyopathy Diltiazem for arrhythmias in heart failure, 775, 777, 779t, 795 for feline cardiomyopathy, 811-813, 811t, XIII:751 for hypertensive crisis, XIII:840 for supraventricular tachyarrhythmias, 723-724, 725f, 726, XIII:728, XIII:729 for syncope, 712t Dimenhydrinate (Dramamine) as antiemetic, XIII:682-683 toxicity of, XIII:229 Dimethyl sulfoxide (DMSO) for amyloidosis, 867 for craniocerebral trauma, XIII:184 for feline lower urinary tract disease, XIII:889t, XIII:892 topical otic, 432t Dioctyl calcium sulfosuccinate, in cats, XIII:651t Dioctyl sodium sulfosuccinate (DSS), XIII:650, XIII:651t for ear flushing, 436-438 Diphenhydramine for anaphylaxis, 419 for cholinesterase inhibitor toxicity, 121 for vestibular disease, 1101 in cats, XIII:544t topical use of, 411, 411t toxicity of, XIII:229 Diphenylmethane diisocyanate toxicity, 140 Dipivefrin, for feline glaucoma, 1210t Dipteryx odorata, 151t Direct mutation tests, 1055-1058, 1056t, 1057t Dirlotapide (Slentrol), 195 Dirofilaria immitis. See also Heartworm disease life cycle of, 837-838 Dirofilariasis. See Heartworm disease Disc disease. See also Intervertebral disc disease epidural anesthesia and analgesia for, 15-16 Discoid lupus erythematosus, topical immune modulators for, 422 Disinfectant(s) for canine influenza, 1294 for feline calicivirus, 1287 for feline viral disease control, 1300 in small animal practice, XIII:258-262 resistance to, XIII:259

Disseminated intravascular coagulation (DIC) diagnosis and treatment of, 287-291, 289f, XIII:190-194, XIII:191t differential diagnosis of, XIII:193 diseases associated with, 289b in cats, XIII:102 in gastric dilatation-volvulus, 81-82, XIII:168 in shock, XIII:144-145 laboratory findings in, 290t thrombocytopenia and, XIII:439 with immune-mediated hemolytic anemia, 268, 271 Distemper canine conjunctivitis from, 1177, XIII:276, XIII:1054 neonatal diarrhea from, XIII:627t thrombocytopenia from, XIII:441t vaccine recommendations for, 1272, 1273t feline (See Panleukopenia) Distichiasis, 1184, XIII:1072 causing epiphora, XIII:1057 Diuretic(s) adverse effects of, 774 for dilated cardiomyopathy, in dogs, 793-794 for feline cardiomyopathy, 811-814, 811t, 818 for heart failure, 773-774 for hypertension, XIII:840 for noncardiogenic pulmonary edema, 665 for oliguria and anuria, 880-881, 880t for refractory edema, XIII:754-755 for toxin-induced acute renal failure, 161b hyperkalemia and hyponatremia with, XIII:375 interactions of, with nutrients, XIII:712 outpatient therapy, XIII:750 with ACE inhibitors, 783-784 DL-methionine, Heinz body anemia from, XIII:421 DMSO. See Dimethyl sulfoxide (DMSO) DNA analysis of, XIII:246 based diagnostic techniques, XIII:455 handling and storage of, XIII:457 DNA testing, for inherited canine diseases, XIII:909-913 DNA vaccination, for malignant melanoma, 381 Doberman pinscher(s) cardiomyopathy in, 796, 800-803, 801f cervical spondylomyelopathy in, 1088-1093 chronic rhinitis and pneumonia in, XIII:449 inherited copper hepatitis, 560-561 occult cardiomyopathy in, XIII:756-760 syncope in, 710-711 von Willebrand’s disease in, XIII:434-436 Dobutamine (Dobutrex) for cardiogenic shock, 777 for dilated cardiomyopathy, in dogs, 796 for feline cardiomyopathy, 813 for feline myocardial failure, XIII:765 for heart failure, 775 for noncardiogenic pulmonary edema, XIII:812 for refractory heart failure, XIII:755 for shock, 6, 665 in cats, XIII:101 use of, in gastric dilatation-volvulus, 78 Docetaxel (Taxotere), as chemotherapy, 312t, 313 DOCP. See Deoxycorticosterone pivalate Dog erythrocyte antigens (DEAs), 260 Dog(s). See also under Canine(s); specific disorders microchip implantation site for, XIII:94t Dolasetron (Anzemet) for acute renal failure, 881 for pancreatitis, 536 for vomiting cats, 574 use of, with chemotherapy, 308 Domperidone, XIII:615, XIII:615t Donnan effect, 61-62

  Index Dopamine (Intropin) for acute renal failure, XIII:176 for cardiogenic shock, 777 for disseminated intravascular coagulation, XIII:193 for feline myocardial failure, XIII:765 for heart failure, 775 for hypotensive shock, 6, 665 for noncardiogenic pulmonary edema, XIII:812 for oliguric renal failure, 880t, 881, XIII:849 for pancreatitis, in cats, 540, XIII:703 for shock, XIII:143 in cats, XIII:101 role of, in hyperadrenocorticism, XIII:364 use of, in gastric dilatation-volvulus, 78 Dopamine agonist agents, for abortion, XIII:951-952, XIII:953t Dopexamine, for therapy of shock, XIII:143 Doppler, for fetal monitoring, 994f Doramectin for demodicosis, 394 for sarcoptic mange, 393 toxicity of, 125-127 use of, in dermatology, 391-392 Dorzolamide, for feline glaucoma, 1210t, 1211 Doxapram, for airway evaluation, 619, 628 Doxorubicin (Adriamycin) effects of, on kidney, 930 for anal sac tumors, 384 for canine lymphoma, 336, 337t for feline gastrointestinal lymphoma, 342, 342t for hemangiosarcoma, 330-331 for insulinoma, XIII:360 for mammary cancer, 365, 368 for osteosarcoma, 361t for soft-tissue sarcomas, 326-327 liposomal formulation of, 312-313 poikilocytosis from, XIII:423 toxicity of, 308 use of, 310, XIII:463, XIII:468-469 Doxycycline effect of, on dental enamel, 648 for anaplasmosis, 1251 for bacterial pneumonia, 661, 661t, 1226t, 1228 for bartonellosis, 1244 for Bordetella bronchiseptica infections, 647-648 for chronic bronchitis, 644 for chronic rhinitis, 615, 617-618 for feline calicivirus, 1286 for feline chlamydiosis, 1186-1187 for heartworm disease, 841 for hepatozoonosis, XIII:311 for infectious causes of thrombocytopenia, 282t-283t for leptospirosis, 1239, XIII:309 for mycoplasmosis, 1247 for osteosarcoma, 362 for tear film disturbances, 1196 for upper respiratory tract infections, 1226t, 1228 for urinary tract infections, 921t, 1226, 1226t induced esophagitis, 483, 644 minimum inhibitory concentrations (MIC) of, XIII:35t Drain, peritoneal, 72-76, 74f Dressing, of degloving or shearing wounds, XIII:1033-1035 Droperidol, adverse reactions of, in dogs, XIII:240t Drug. See Chemotherapy; Poisoning; specific drugs Drug administration, during pregnancy, in dogs, XIII:933 Drug dosages, 1306-1334 in cats, XIII:103 Drug eruptions, cutaneous, XIII:557t therapy for, XIII:556-559 Drug monitoring, XIII:26-32 formula for calculating dosing regimens, XIII:29t interpreting results of, XIII:31-32

1355

Drug poisoning, incidence of, XIII:206t Drug reaction(s) adverse, 99-104, 103b, XIII:239-242, XIII:240t herbal, 150 response to, XIII:239-242 associated with causing pancreatitis, XIII:697-698 causing blepharitis, 1182 causing crystalluria and uroliths, XIII:846t causing hematologic dyscrasias, 272, 274 causing hepatotoxicity, 544b causing liver disease, 566-569, 567b, 568t causing pancreatitis, 536 causing platelet dysfunction, 294t, XIII:444, XIII:445t causing pregnancy loss in the bitch, 988, 988b in the queen, 1045 causing splenic congestion, XIII:521t cutaneous, XIII:556-559 ocular, XIII:1054 to allergen-specific immunotherapy, 417-419 to calcineurin inhibitors, 423-434 to cyclosporine, 387-388 to iohexol, 870-871 to long term use of glucocorticoids, 404-405 to pentoxifylline, 398 with herbs, 153-154 Drug resistance, gene therapy, XIII:496 Drug therapy See also specific disorder aerosol delivery of steroids and ­bronchodilators, 656-657 antineoplastic, 305-314, XIII:462-465, XIII:465-478 avermectin, 390-394 causing anisocoria, 1172, XIII:1047-1048 causing neonatal diarrhea, XIII:627t cyclosporine, 386-388 effect of on thyroid function tests in dogs, 187t on urine protein, 860 on urine specific gravity, 868 empiric antibiotic, 1225-1229, 1226t failure of, XIII:263t for canine pregnancy termination, 1031-1033 for CPR, 31-32 for feline leukemia virus, XIII:283-284 for the eye, 1145-1149, 1147t, 1148t, 1150-1153, 1150t glucocorticoid, 400-405 rational use of in infectious disease, 1230-1233 immunosuppressive, 254-259, XIII:510-513 vaccine recommendation with, XIII:254-255 interactions of, with nutrients, XIII:712 interferon, 389-390 intravitreal, 1148, 1148t pentoxifylline, 397-400 resistance to, in chemotherapy, XIII:479-482 subconjunctival, 1146, 1147t, 1150-1151 topical ear, 428-433 unsafe use of, XIII:240 ursodeoxycholic acid, 563-565 Drug toxicity. See also Toxicity(ies); specific agent (e.g. Digoxin) and exposures, 92-94 and reactions reporting, 99-104, 101b chemotherapy See (Chemotherapy) otic, 432-433, 433b over-the-counter, XIII:227-231 Drug-herb interactions, 153-154 Drugs of abuse, websites for at-home tests, 107b Drugs, formulary of, 1306-1334 Dry matter, XIII:74 Drying agents, for ears, 430t Duel-lead dual-chamber pacing, 719-721, 720f Duloxetine, 958-959 Duoxo micellar solution, 430t Dysautonomia, XIII:957-959, XIII:957t, XIII:958f megaesophagus from, 489, 491 Dyscoria, 1201, 1201f Dyshematopoiesis, XIII:417t

1356

  Index

Dysmyelopoiesis, 275 Dysoxia, 596-598, 597b Dysphagia clinical signs of, 479t from megaesophagus, XIII:602-607 from stomatitis and faucitis, in cats, XIII:600 oropharyngeal, 479-482 with laryngeal paralysis, 627 Dysplasia, of elbow, in dogs, XIII:1004-1014 Dystocia causing pregnancy loss in the queen, 1043 management in the bitch, 992-998 E Ear. See also Deafness; Otitis cleaning, 429, 430t, 436-438 drying agents, 430t flushing techniques, 436-438, XIII:583-584 polyps (See Nasopharyngeal disorders, polyps) rinses and lotions, 428 topical therapy for, 428-433 tumors, 1099, XIII:968 Ear mite(s) Otodectes cyanotis, differential diagnosis for, in cats, XIII:565t treatment of, 393, 436 Easter lily toxicity, 110, 143, XIII:216 Ebstein’s anomaly, 762, 764 Echocardiography comparison of, to computed tomography, XIII:709 for boxer cardiomyopathy, 798 for dilated cardiomyopathy, in dogs, 793 for Doberman pinscher cardiomyopathy, 801-802, 801f, XIII:758 for endocarditis, XIII:770 for feline cardiomyopathies, 809-815, 810t, 816, 817f for feline congenital heart disease, XIII:739t for feline heartworm disease, 834-835, XIII:785-786, XIII:786f for infective endocarditis, 789 for mitral valve dysplasia, 767-768, 767f for myocarditis, 805 for patent ductus arteriosus, 744 for pericardial effusion, 826-827, 827f, XIII:774, XIII:774f for pulmonary hypertension, 699-700, 699f, 700f, 701f for pulmonary thromboembolism, 691 for pulmonic stenosis, 753-755 for screening and staging heart disease, 772-774 for subaortic stenosis, 758-761, 758f for tricuspid valve dysplasia, 763-764, 764f for valvular heart disease, 782-783 for ventricular septal defect, 753f, 754f normal cardiac, 810 Eclampsia, 1001-1002 Ecstasy toxicity, 144 Ectopic cilia, XIII:1072 Ectopic ureters. See Ureters, ectopic Ectropion, 1184 Education, of client, to enhance treatment compliance, XIII:22-26 Effusion abdominal, hepatobiliary disease and, XIII:661 pericardial (See Pericardial effusion) pleural, 675-684, XIII:819-825 Ehrlichiosis, XIII:298-299 causing nonregenerative anemia, 272 cytograms and histograms of leukocytes demonstrating, XIII:386f feline, XIII:299 granulocytic, XIII:298-300 neutropenia and, treatment of, XIII:271 ocular signs of, XIII:277-278 polymerase chain reaction for, XIII:248 relationship to Bartonella spp. infection, XIII:301t thrombocytopenia from, 282t, XIII:440, XIII:441t vector associated with, XIII:296t Eisenmenger’s physiology, 749

Ejaculation antegrade in the dog, 1049-1050 retrograde in the dog, 1049-1052, 1051t spinal reflexes occurring with, 1050, 1050b Elbow joint anatomy of, in dogs, XIII:1004 dysplasia of, in dogs, XIII:1004-1014 incongruity of, XIII:1006-1014 ELD feeding tube device technique, 590-591, 590f-592f Electrical alternans, with supraventricular ­tachyarrhythmias, 723 Electrocardiography. See also Arrhythmia atropine response test and, XIII:723 bradyarrhythmias and, XIII:722-723 monitoring of after pacer implantation, 718, 719f in calcium administration, 244 in CPR, 32 in gastric dilatation-volvulus, 78 in pericardiocentesis, 828 of feline arrhythmias, 732, 733t of supraventricular tachyarrhythmias, 722-723, 724f, 725t, XIII:728t pacing and, 44-47, 44f-46f pericardial effusion and, XIII:773-774, XIII:774f with boxer cardiomyopathy, 797 with dilated cardiomyopathy, in dogs, 793 with feline congenital heart disease, XIII:739t with hyperkalemia from feline urethral obstruction, 951-952 with mitral valve dysplasia, 766 with myocarditis, 805 with occult cardiomyopathy, XIII:758 with pericardial effusion, 826 with pulmonary hypertension, 699 with pulmonic stenosis, 752 with tricuspid valve dysplasia, 762-763, 763f with valvular heart disease, 782 Electrodiagnostic testing, for dysphagia, 480-481 Electroencephalography, with FIV infection, XIII:290 Electrolyte(s). See also specific electrolyte e.g. Potassium balancing, in cats in critical care, XIII:100 fractional excretion of, in urine, XIII:16-17 Electromyelogram and neurologic manifestations of ­hypothyroidism, XIII:975 for dysphagia, 481 Electron microscopy, for cancer diagnosis, XIII:454-455 Electrophysiologic testing for bradyarrhythmias, XIII:722-724 for supraventricular tachyarrhythmias, 723, XIII:726-728 Electroretinography, for evaluating blindness, 1164 Elimination diets, XIII:532-533, XIII:533t ELISA. See Enzyme-linked immunosorbent assay Elizabethan collar, for oxygen delivery, 598 Elliptocytosis, XIII:417t autosomal recessive inheritance of, XIII:910t Elongated soft palate, 620 Emboli, endocarditis and, XIII:769 Emepronium bromide, for lower urinary tract disease, XIII:901 Emergency care. See also under Critical care anesthesia for, procedures in, XIII:122-126 cardiopulmonary resuscitation (CPR) in, open chest, XIII:147-149 craniocerebral trauma in, XIII:178-186 defibrillation in, XIII:150-153 for acute abdomen, XIII:160-164 for eye, XIII:1090-1094 (See also EVOLVE) for hypertension, XIII:840 for hypocalcemia, XIII:341-342 for noncardiogenic pulmonary edema, 663-665 for open fractures, 83-85, 84b, 84t, XIII:170-172 for pleural effusion, 675-676

Emergency care (Continued ) for pneumothorax, 685-689 for spinal cord disease, XIII:186-189 for status epilepticus, 1062-1065, 1063f for toxicities, XIII:207-211, XIII:207t, XIII:212-216 for tracheal collapse, 633 for uremic crisis, XIII:849-850 for ventricular arrhythmias, XIII:731-732, XIII:733-737 for wheezing cat, 650, 654, 657 Emesis. See Vomiting Emetics, 112-113, 113t Enalapril (Enacard, Vasotec) adverse effects of, 794-795 effect of, on proteinuria, XIII:852 for dilated cardiomyopathy, in dogs, 794-795, 794t for feline cardiomyopathy, 811t, 813 hypertrophic, XIII:751-752 for heart failure, 772-774, 779t, 784 for hypertension, 716, XIII:840 in cats with hyperthyroidism, 276t with renal disease, 912, 912t for syncope, 712t for ventricular septal defect, 750 Encephalitis, diagnosis and treatment of, 1070-1074 Encephalomyelitis, from Borna disease, in cats, XIII:976-978 End points, in clinical trials, 299 Endemic infections, 1222-1223 Endocardial cushion defect, clinical findings with, in cats, XIII:739t Endocardiosis. See Heart failure; Valvular heart disease Endocarditis from bartonellosis, 1242-1243, XIII:300-301 infective, 786-791, 788t, 790b, XIII:768-772 Endocrine diagnostic tests for adrenal disease, 170-172 for thyroid disease, 172-173 Endocrine disorder(s) associated with obesity, 192b cognitive dysfunction and, XIII:53-57 polyglandular, XIII:329-330 urinary tract infection associated with, XIII:878-880 Endodontic disease. See Dental disease Endomyocardial biopsy, for myocarditis, 805-806 Endoparasites. See Parasite(s) Endoscopy brush cytology using, 493-494, 494f for esophageal evaluation, 484-485 for gastrinoma, XIII:618 for gastrostomy tube placement, 908 for nasopharyngeal evaluation, 623 for tracheal evaluation, 632-633 for transcervical canine insemination, 983-985 of urinary tract, 938 vaginal, 978-979 Endosurgery, 965 Endothelial degeneration, corneal edema from, 1160, 1160f Endothelial dystrophy, XIII:1068-1069 Endothelin inhibitors, for progressive renal failure, XIII:863 Endothelin receptor antagonists, 701 Endotoxemia, thrombocytopenia from, 283t Endouroscopy, of urinary tract, 938 Enemas, for constipation, in cats, XIII:650, XIII:651t Enilconazole for fungal rhinitis, 613-614 for Malassezia dermatitis, XIII:576 topical rinse for dermatophytosis, 459t Enoxaparin as anticoagulant therapy, 26-27 for prevention of thrombi, 694

Enrofloxacin (Baytril). See also Fluoroquinolone(s) adverse reactions of, in dogs, XIII:240t associated liver disease, 568t concentration of, in tissues, XIII:45t effect of, on theophylline metabolism, 644 for bacterial pneumonia, 661 for Bartonella spp. infections, XIII:306 for brucellosis, 986 for chronic bronchitis, 644 for mycoplasmosis, 1247 for neutropenia, XIII:269t, XIII:271 for otitis externa, from Pseudomonas, 435t, XIII:264, XIII:587 for sepsis, XIII:273t for ulcerative colitis, 522 for upper respiratory tract infections, 1228 for urinary tract infections, 1227 lameness from, 522 minimum inhibitory concentrations for, XIII:35t, XIII:42t otic, 431t theophylline and, XIII:804 tissue concentrations of, XIII:45t use and misuse of, XIII:41-48 Enteral feeding methods of, XIII:71t with esophageal tubes, 589-593 with sepsis, XIII:275 Enteral nutrition, 18-23, XIII:71-74. See also Microenteral nutrition for the cancer patient, XIII:461 Enteritis chronic colitis, 515-520 from inflammatory bowel disease, 501-506 from parvovirus, in cats, 1304-1305 from protein-losing enteropathy, 512-515 from tritrichomonas, 506-509 responsive to tylosin, 506-509 Enteroclysis, XIII:613 Enterococcosis bacterial resistance of, XIII:264-265 sepsis and, XIII:273 treatment of, XIII:265 Enterococcus spp., causing urinary tract infections, 919, 920t, 1226 Enteropathy, dietary sensitivity, XIII:632-637 Entropion, 1184 Environmental factors, influencing vaccination, XIII:252-253 Enzyme-linked immunosorbent assay (ELISA) definition of, and terms used with, XIII:9t for atopy, XIII:560-564 for Bartonella spp., XIII:305 for canine influenza, 1293 for feline coronavirus, XIII:291-292 for feline leukemia virus, XIII:280-281 for luteinizing hormone, 977 for parvovirus, XIII:630 for pythiosis, 1269 methods and interpretation of, XIII:8-11 Enzymes, as chemotherapy, 310 Eosinophil-T lymphocyte interactions, in feline bronchitis and asthma, 651 Eosinophilic colitis, 516, XIII:645 Eosinophilic disease complex cyclosporine for, 409 tacrolimus for, 409 EPA, reporting adverse drug events to, 99-104 Ephedra toxicity, 151 Ephedrine for therapy of shock, XIII:143 for urinary incontinence, 957t toxicity, XIII:153-157, XIII:156 Epi-Otic, 430t Epidemic infections, 1222 Epidermal necrosis, from drugs, XIII:557t, XIII:558 Epidural anesthesia and analgesia, 15-16, XIII:126-131. See also EVOLVE for neurologic and musculoskeletal pain, 1128t for vaginal surgery, 1012 technique for, XIII:128-130

  Index Epilepsy. See also Seizure(s) in cats, XIII:963-966 in dogs, XIII:959-963 new anticonvulsant drug therapy for, 1066-1069 treatment of status epilepticus, 1062-1065, 1063f Epinephrine. See also under Catecholamine(s) for anaphylaxis, 419 for CPR, 31 for feline glaucoma, 1210t, 1211 for hypotensive shock, 6 toxicity of, from inhalers, XIII:154 Epiphora, XIII:1055-1057, XIII:1055t, XIII:1056f. See also EVOLVE Epirubicin, as chemotherapy, XIII:475 Episcleral redness, 1177-1178, XIII:1044 Episcleritis, in dogs, 1190-1192, 1191t Episclerokeratitis, granulomatous nodular, XIII:1069-1070 Episioplasty, 1010, 1014, 1015f Episiotomy, 1012-1013, 1013f, 1015-1018, 1016f Epithelial débridement, 1198-1199 Epithelial dystrophy, XIII:1068 Epitheliotropic cutaneous lymphoma, ­immunophenotyping for, XIII:506-507 Epogen. See Erythropoietin Epostane, for abortion, XIII:953 Eprinomectin toxicity, 125-127 Epsiprantel, adverse reactions of, XIII:240t, XIII:241t Eptifibatide, as antiplatelet therapy, 25 Erection intermittent in male castrated dogs, 1053 normal canine, 1049 Ergocalciferol, 245, 245t for hypoparathyroidism, XIII:343-344 Ergonovine maleate, for postpartum hemorrhage, 1000t Erythema multiforme causing blepharitis, 1182 nonsteroidal immunosuppressive therapy for, XIII:536 Erythrocyte(s) canine, XIII:414-415 cytograms and histograms of, XIII:381-390 feline, XIII:414-415 hereditary disorders of, XIII:414-420 (See also EVOLVE) nucleated, on scattergrams and histograms, XIII:383 Erythroderma, from drug(s), XIII:557-558, XIII:557t Erythromycin, as gastric prokinetic agent, XIII:615t, XIII:616 Erythropoietin, XIII:403 adverse effects of, 917 for anemia from acute renal failure, XIII:177 from chronic kidney disease, 874t, 877, 916-917 from feline retroviruses, 1280 Escherichia coli causing metritis, 1000 causing neonatal diarrhea, XIII:626, XIII:627t causing urinary tract infections, 919, 920t, 921-923, 1226 infectious disease emergence and, XIII:244 minimum inhibitory concentrations (MIC) for, XIII:35t, XIII:42t polyuria from, XIII:832 role of in infective endocarditis, 788, 788t in ulcerative colitis, 521 urinary tract infection with, XIII:884 Esmolol (Brevibloc) for feline ventricular tachycardia, 818 for supraventricular tachyarrhythmias, 725-726 Esophageal disease megaesophagus as, 486-492, 487b, XIII:602-607 metoclopramide for, XIII:614-615

1357

Esophageal feeding tubes, 589-593, XIII:597-599, XIII:597f for chronic kidney disease, 873t Esophageal perforation, causing pneumothorax, 687 Esophageal rupture, 485 Esophageal stricture, 482-486 Esophageal tube applicator technique, 592-593 Esophagitis, 482-486 Esophagostomy tube(s), XIII:71t, XIII:72, XIII:72t for nutritional support, in cats, XIII:687-690 Esophagus. See also Megaesophagus disorders of, 487b, XIII:602t function of, 486-487 functional anatomy of, XIII:602-603 perforation of, in dogs, XIII:825-826 stricture of, XIII:607-608 Essential fatty acid(s) comparison of, found in various oils, XIII:539 for sebaceous adenitis, 452 in cats differential diagnosis for deficiency of, XIII:565t for atopic disease, XIII:566 for dermatology, XIII:538-542 for pruritus, 408, XIII:544 supplements, 396 Essential oil toxicity, 152-153, 152t Estradiol benzoate, for canine pregnancy ­termination, 1031 Estradiol cypionate for canine pregnancy termination, 1031 toxicity of, 147-148 Estradiol, role of, in hyperadrenocorticism, 222t Estriol, for urinary incontinence, 957t Estrogen adverse effects of, 958, 1008, 1031 concentrations, during false pregnancy, 990 for canine pregnancy termination, 1031, XIII:949-950 for false pregnancy, 991 for urinary incontinence, 956-958, 957t Estrogen toxicity, 147-149, 148t-149t Estrus abnormal, XIII:926-927 in dogs, 975-975 prolonged, in cats, XIII:930 suppression of, in the bitch, 1024-1030 Etanercept, for feline infectious peritonitis, 1297t Ethanol ablation, for hyperparathyroidism, 250 Ethanol, for ethylene glycol toxicity, 114t, 115, 132, 161 Ethyl lactate shampoos, 414, 414t Ethylene glycol toxicosis, 114t, 115, 160b, 856b, 858-859 diagnosis and treatment of, 130-132, 160-162 exposure, 97t metabolism in, 131f prognosis for, 855 Etodolac (Ectogesic) for neurologic and musculoskeletal pain, 1128t for ocular diseases, 1151t for osteoarthritis, XIII:1019 Etomidate, XIII:124, XIII:125t Etretinate as chemotherapy, XIII:476 for sebaceous adenitis, 452, XIII:573 Eucoleus boehmi, 666 Euonymus europaeus, 151t Eupatorium spp., 151t Eurytrema procyonis, 542, XIII:705 Evening primrose oil, as essential fatty acid, XIII:539 Everted laryngeal saccules, 621 Evidence-based medicine, 872-873, XIII:2-8 Evisceration, for feline glaucoma, 1212 Examination, ocular, 1140-1145

1358

  Index

Exercise for physical therapy and rehabilitation, 1131-1135 recommendations for, in pregnant dogs, XIII:931-932 role of in canine diabetes, 196 role of in obesity, 194 Exocrine pancreatic insufficiency (EPI) diagnosis and treatment of in cats, 540-541 in dogs, 531-534 nutritional management of, XIII:657 Exocrine pancreatic neoplasia, in cats, 541-542, XIII:704 Exophthalmos, XIII:1086-1089. See also EVOLVE Exploratory celiotomy. See Celiotomy External skeletal fixation, in open fractures, 85 Extraocular muscle myositis, 1113 Extraocular polymyositis, XIII:1088, XIII:1090 Extravasation, of antineoplastic drugs, XIII:465 Eye. See also under Ophthalmic disease(s); specific disorder alkali burns to, XIII:1092 exophthalmos of, XIII:1086-1089 (See also EVOLVE) red algorithm for, XIII:1042f causes of, 1175-1178, 1176f cornea, 1158-1159, 1159f, 1163t differential diagnosis of, XIII:1042-1045 tear film disturbances of, 1193-1196 tearing of, XIII:1055-1057 (See also EVOLVE) techniques for examination of, 1140-1145, 1170-1171 Eyelid diseases, 1178-1184, XIII:1051-1052 lacerations, XIII:1090-1091 neoplasia, 1154-1155 pigment changes of, 1182-1183 F Factor VII deficiency, genetic tests for, 1056t Factor XI deficiency, genetic tests for, 1056t False pregnancy, in the bitch, 990-991 Famciclovir, for feline herpesvirus, 1189 Familial macrocytosis, XIII:417t Familial microcytosis, XIII:417t Famotidine for gastric ulceration, 500 for Helicobacter spp. infection, 495f, 496 for uremic gastropathy, 916 for vomiting cats, 574 toxicity of, XIII:229 use of, during shock, 7 Fanconi syndrome polyuria and polydipsia in, 846t urine collection and, XIII:13t Fat emulsions, composition of, for parenteral use, XIII:82t Fat(s), dietary, XIII:654 for diabetes mellitus management, 205t, 206 recommendations in heart disease, 706 Fatty acids. See also Essential fatty acid(s) for chronic kidney disease, 873t, 875, 885 omega-3 for heart disease, 779t, 796, XIII:714-715 for hip dysplasia, 1123 use of, in diabetes mellitus, 206 requirements during pregnancy and lactation, 1004 Faucitis, feline, XIII:600-602 FDA food recall and role of, 165-168 reporting adverse drug events to, 99-104 Febreze, 110 Fecal α1-proteinase inhibitor testing, 502, 513 Fecal elastase testing, 532 Fecal examination(s) for respiratory parasites, 666-671 for tritrichomonas, 510 Fecal proteolytic activity testing, 532 Feeding tube(s). See Nutrition, feeding tube Felbamate, for seizures, 1066-1067 Feline caudal stomatitis, 476-478

Feline coronavirus. See also Feline infectious peritonitis (FIP) control of, 1300t, 1303-1304, 1303b, 1304b tests, 1304 Feline cowpox, 442-443 Feline facial pheromone fraction F3 (Feliway), 950 Feline histiocytic diseases, 351 Feline immunodeficiency virus (FIV) causing nonregenerative anemia, 273 control of, in catteries, 1300t, 1302, 1302t diagnosis and treatment of, 1278-1283, 1281t, XIII:284-287 neonatal diarrhea and, XIII:627t neurologic signs of, XIII:286 ocular signs of, XIII:278 polymerase chain reaction for, XIII:248 prevention of, XIII:286-287 skin lesions from, 442 thrombocytopenia from, 282t, XIII:440, XIII:441t vaccine recommendations for, 1276t, 1277, 1279 cats with, XIII:255 Feline infectious peritonitis (FIP) control of, in catteries, 1300t, 1303-1304 diagnosis and treatment of, 1295-1299 neonatal diarrhea from, XIII:627t neutrophil dysfunction in, XIII:449t ocular signs of, XIII:278 pericardial effusion from, XIII:773 polymerase chain reaction for, XIII:248 prevention of, 1303-1304 thrombocytopenia from, 282t, XIII:440 use of glucocorticoids with, 1231 vaccination of, 1277, 1297-1298, 1300t, 1303, XIII:251 Feline interferon for feline infectious peritonitis, 1296, 1296b for feline retrovirus, 1281t, 1283 Feline leukemia virus (FeLV) control of, in catteries, 1300t, 1301-1302, 1302t diagnosis and treatment of, 1278-1283, 1281t, XIII:280-284 diagnosis of, 1301-1302, 1302t polymerase chain reaction for, XIII:248 test recommendations for, XIII:282t gastrointestinal lymphoma and, 340 immune-mediated hemolytic anemia and, XIII:430 in critically ill cats, XIII:102-103 mediastinal lymphoma and, 355, 355f neonatal diarrhea from, XIII:627t neurologic signs of, XIII:288 neutrophil dysfunction from, XIII:449t ocular signs of, XIII:278 pathogenesis of, XIII:281t renal lymphoma and, 928 skin disease from, 442 thrombocytopenia from, 282t, XIII:440, XIII:441t vaccination fibrosarcoma from, XIII:498 recommendations for, 1276t, 1277, 1279 Feline lower urinary tract disease (FLUTD). See also under Cystitis anticholinergic agents for, XIII:899-902 bacterial infection and, XIII:10-19 diagnosis and treatment of, 944-950 effect of early neutering on, 1020-1021 nonobstructive idiopathic, XIII:888-893, XIII:889t obstructive, XIII:849-850 urate, dietary recommendations for, XIII:843t, XIII:846 Feline panleukopenia. See Panleukopenia Feline papillomavirus, 442 Feline pox virus, 1300t Feline pruritus therapy, 405-410 Feline triaditis syndrome, 578 Feline urologic syndrome. See Feline lower urinary tract disease (FLUTD) Feline vaccine-associated sarcoma, 332-335 Feline viral skin disease, 441-443

Feline(s). See also under Cat(s); specific disorders vaccination recommendations for, XIII:250 FeLV. See Feline leukemia virus (FeLV) Fenbendazole adverse reactions to, in dogs, XIII:240t for bronchopulmonary parasites, 667-671 for chronic diarrhea, 508 for Filaroides hirthi, 668 for inflammatory bowel disease, 503 for interstitial lung disease, 674 for nasal parasites, 666 for Oslerus (Filaroides) osleri, 668 Fenoldopam, for oliguria and anuria, 880t Fentanyl adverse reactions of, in dogs, XIII:240t constant-rate infusion (CRI) of, 88-89, 823 epidural, XIII:127-128 for arterial thromboembolism, 823 for epidural analgesia/anesthesia, dosage of, XIII:127t for feline idiopathic cystitis, 947t for neurologic and musculoskeletal pain, 1128t for pain management, 11, 11t, 12f-13f, 88-89, XIII:59-60 patch, 11 as palliative therapy for cancer, XIII:477 in cats, XIII:105 use of, with gastric dilatation-volvulus, 80 Fentanyl lidocaine ketamine (FLK) CRI, 12f-13f, 88-89 Fenthion, adverse reactions of, in dogs, XIII:240t Ferret(s) hyperadrenocorticism in, XIII:372-374 (See also EVOLVE) insulinoma in, XIII:357-361 (See also EVOLVE) Ferrous sulfate, for iron deficiency anemia, 916 Fertility and pregnancy loss in the bitch, 987-989 in dogs, 974-979, 975t Fertilizer(s) exposure to, 93 toxicity of, 160b, XIII:221-222 Fetus(es) causes for dystocia, 996 dead, medical management of dystocia with, XIII:939 defects of, in the feline, 1045, 1045f extrauterine, in the queen, 1043 loss in the bitch, 986-989 monitor for, 993-994 Fever antibiotics for, with neutropenia, XIII:270t from hepatozoonosis, XIII:311 relapsing, vector associated with, XIII:297t therapy of neutropenia with, XIII:268-269 Fiber dietary sources of, XIII:658t for chronic colitis, 517-518 for diabetes management, 196, 204-205, 205t for inflammatory bowel disease, 503 Fibrin formation of, in pleural disease, 680 in disseminated intravascular coagulation, 287-289, 288f, 289f, XIII:192 Fibrinogen degradation products (FDP) D-dimers, 691 in disseminated intravascular coagulation, XIII:192 Fibrinogen, in disseminated intravascular coagulation, 288f, 289f, XIII:192 Fibroadenoma, mammary, 364t Fibropapilloma, 442 Fibrosarcoma. See also Neoplasia; Radiation therapy; Sarcoma feline, vaccine associated, XIII:498-500 nasal, 616, XIII:500t of larynx, XIII:503t orbital, 1154 paranasal, XIII:501t Fibrosing pleuritis, 680-681 Filaroides hirthi, 668-669

Finasteride (Proscar) for benign prostatic hypertrophy, 1047 for prostatitis, 1048 Fine-needle aspiration of liver, 548, 552, 571 of mast cell tumors, 374 of nasopharynx, 623 technique for cytology, 301-302 Finoff transilluminator, 1140 FIP. See Feline infectious peritonitis (FIP) Fipronil toxicity, 123-124, XIII:234-235 Firocoxib, for neurologic and musculoskeletal pain, 1128t Fish oil, XIII:540 Fishing sinkers, 127 Fistula, rectovaginal vestibular, 1014 FIV. See Feline immunodeficiency virus Flail chest, 87 Flatulence, 523-527 Flatus, 523-727 Flavoxate, for lower urinary tract disease, XIII:900t, XIII:901-902 Flea allergy to, differential diagnosis for, in cats, XIII:565t as vectors in bartonellosis, 1242-1244 treatments for, 394 Flea and tick products, active ingredients in, XIII:232t Flea product toxicity, XIII:231-235. See also Toxicity(ies); individual chemical e.g. Pyrethrins Florida spots, XIII:1070 Florinef. See Fludrocortisone acetate Flow cytometry, laboratories performing, 338t Fluconazole for central nervous system cryptococcosis, 1072-1073 for dermatophytosis, 461 for fungal rhinitis, 614, 625 for Malassezia infections, 455t for respiratory tract fungal disease, XIII:817-819 Fludrocortisone acetate (Florinef), for hypoadrenocorticism, 234 Fluid balance, assessment of, 48-49 Fluid dynamics, 61-62 Fluid requirements, definition of, XIII:14t Fluid therapy, 48-54, XIII:61-65 balance of, in cats in critical care, XIII:99-100 colloids for, 61-67, XIII:66-69, XIII:131-136 complications of, 53-54 for acute renal failure, 879-881, XIII:175 toxin-induced, 161b for anaphylaxis, 419 for chronic kidney disease, 874t, 875-877 for diabetic ketoacidosis, 216, 217b for dystocia, in dogs, XIII:937-938 for feline urinary obstruction, 953 for gastric dilatation volvulus, 78-79, 78t for hepatic lipidosis, 573 for hypercalcemia, 346, 346f, XIII:347 for hypoadrenocorticism, 233 for noncardiogenic pulmonary edema, 664 for pancreatitis, 536 for parvoviral enteritis, XIII:630 for shock, 4-6, XIII:141 for traumatic brain injury, 35, 35t in CPR, 32 monitoring of, 53-54 physiology of, XIII:131-132 potassium supplementation and, 50t requirements, 52, 52b, 52t technique for administration of, XIII:61-65 vascular access techniques for, XIII:118-121 with feline urinary calculi, 933 Flumazenil, XIII:122-123, XIII:125t Flumethasone, comparison of, to other glucocorticoids, 401t Flunixin meglumine (Banamine) causing nephrotoxicity, 162 for pain management, 14, 14t for parvovirus, XIII:631 toxicity of, XIII:214-215 Fluocinolone, topical otic, 432t

  Index Fluorescein dye testing, 1144 with corneal discolorations, 1158-1163 Fluorescent dye, in ethylene glycol, 132 Fluoride, XIII:208t Fluorinated quinolones. See Fluoroquinolone(s) Fluoroquinolone(s) adverse reactions to, XIII:47 concentration of, in tissues, XIII:45t drug interactions with, XIII:47 for lower respiratory tract infections, 1226t, 1228 for musculoskeletal infections, 1226t, 1228-1229 for otitis, 435, 435t for Pseudomonas spp. aeruginosa, XIII:264 for pyoderma, 1227 for upper respiratory tract infections, 1228 for urinary tract infections, 920-921, 920t, 921t, 1227 resistance of, XIII:43 use and misuses of, XIII:41-48 Fluoroscopy for assessment of gastrointestinal motility, XIII:612, XIII:613 for balloon pericardiotomy, 830 for esophageal evaluation, 483, 489 for tracheal collapse, 638-641, 638f, 639f, 640f for transvenous pacer placement, XIII:199 for urethral stenting, 966-967, 966f, 967f urethral, 970f urinary bladder, 969f with uroliths, 940 Fluorouracil (5-FU) administration protocol for, XIII:464 as chemotherapy, XIII:468 for mammary cancer, 365 toxicity in cats, 309 Fluoxetine HCl (Prozac) for acral lick dermatitis, 473, XIII:555 for feline idiopathic cystitis, 947t for feline pruritus, 408, XIII:544 for sensory mutilation, XIII:91, XIII:92t Fluprostenol, for canine pregnancy termination, 1032 Flurbiprofen for anterior uveitis, 1205, 1206t for ocular diseases, 1151-1152, 1151t Flutamide, for benign prostatic hypertrophy, 1047 Fluticasone propionate (Flovent) for canine chronic bronchitis, 643 for feline chronic bronchitis or asthma, 657 Folate, measurement of, 541, XIII:639 Folic acid, 541 Follicle-stimulating hormone (FSH), during estrus suppression, 1025 Fomepizole (4-methylpyrazole, 4-MP), 114t, 115, 132, 161 Fondaparinux, as anticoagulant therapy, 27 Food. See also Dietary therapy; Nutrition AAFCO nutrient profiles of, 1337-1340 adverse reactions to, 509, XIII:530-536 causing flatulence, 524-526 classification of, by sodium content, XIII:713t contaminated with aflatoxins, 156-159 homemade, for heart disease, XIII:715 information on label of, XIII:79f ingredient information, XIII:75-76, XIII:76f, XIII:76t metabolizable energy of, on labels, XIII:77f nutritional assessment of, labels, XIII:74-80 related poisoning, incidence of, XIII:206t safety of, for pets, XIII:236-238 (See also EVOLVE) toxicosis, 164-168 Food allergy atopy and, XIII:560-561 chronic colitis and, in dogs, XIII:646 definition of, 395 diagnosis and treatment of, XIII:632-637, XIII:633f, XIII:634t (See also EVOLVE) diets for, 395-397, XIII:530-536, XIII:533t, XIII:534f, XIII:632-637

1359

Food allergy (Continued ) diets with novel protein sources, XIII:655t home-cooked diets for, 396 management of diarrhea and, XIII:654-655 nutritional supplements for, 396 relationship to acral lick dermatitis, XIII:552 Food sensitivity, XIII:632-637. See also EVOLVE conditions of, XIII:632t Forceps biopsy, of lower urinary tract, XIII:886-888 Foreign body nasopharyngeal, 624 reactions in skin, 463-464 Formaldehyde, from methenamine, as urinary tract antiseptic, XIII:890 Formulary, of drugs, 1306-1334 Foscarnet, for feline retrovirus, 1281t, 1282 Founder effect, XIII:911 Fracture(s), open classification of, 84t, XIII:170, XIII:170t emergency management of, 83-85, 84b treatment of, XIII:170-172, XIII:171t Fragmented coronoid process, diagnosis and treatment of, XIII:1006-1014 Fructosamine, for monitoring diabetes mellitus, XIII:349 in cats, 210 in dogs, 198, 210 FTY 720, as immunosuppressive agent, 258-259 Fucosidosis autosomal recessive inheritance of, XIII:910t genetic tests for, 1056t Fundic examination, 1143 Fungal culture, technique for, in dermatology, XIII:529-530 Fungal infection(s). See also specific organism causing anterior uveitis, 1203b, 1204 causing blepharitis, 1179 causing myocarditis, 805t causing rhinitis, 610b, 611f, 613-614 dermatophytosis, 457-461 diagnosis and treatment of, 1265-1267 from aflatoxins, 156-159 geographic distribution of, 1266t respiratory tract, XIII:815-819, XIII:816f-817f use of glucocorticoids with, 1231 systemic, antimycotic drug therapy for, XIII:815-819 Fungicides, toxicity of, XIII:221-222, XIII:222t Fungus, effectiveness of disinfectants and antiseptics against, XIII:259t Fur mites, treatments for, 394 Furosemide (Lasix) adverse effects of, 774, 783 causing nephrotoxicity, 160b, 162 diet modification and, effect of, XIII:712 effect of, on renin-angiotensin-aldosterone system, XIII:712 for arrhythmogenic right ventricular, in cats, 811t for ascites from liver disease, 556 for dilated cardiomyopathy in cats, 811-814, 811t in dogs, 793-794 for heart failure, 773-774, 779t, 783-784 acute, 776, 783 in cats, XIII:765-766 outpatient, XIII:750 refractory, XIII:754-755 for hypercalcemia, 346, 346f, XIII:347 for hypertrophic cardiomyopathy, in cats, 811-813, 811t for noncardiogenic pulmonary edema, 665, XIII:811-812 for oliguria and anuria, 880-881, 880t for restrictive cardiomyopathy, in cats, 811t, 814 for syncope, 712t for traumatic brain injury, 36 for ventricular septal defect, 750 hyperkalemia and hyponatremia with, XIII:375 with ACE inhibitors, 783-784 FUS. See Feline lower urinary tract disease

1360

  Index

G Gabapentin for neurologic and musculoskeletal pain, 1128t, 1130 for pain management, 12f-13f, 16 for seizures, 1066, XIII:961t, XIII:962 Gait training, 1132 Galactorrhea, associated with hypothyroidism, XIII:327 Galactosidase, for flatulence, 526 Gallbladder. See under Biliary Gallium nitrate, for hypercalcemia of malignancy, 346f, 347 Gamma globulin, for immune-mediated hemolytic anemia, XIII:432-433 Ganciclovir, for feline herpesvirus, 1189 Garlic ingestion, 110 Gases and fumes poisoning, incidence of, XIII:206t Gasoline toxicity, 134 Gastrointestinal ulceration, shock and, ­treatment of, XIII:143-144 Gastric decompression, 79-80 Gastric dilatation-volvulus (GDV) diagnosis and treatment of, 77-82, XIII:164-169, XIII:166t lactate measurement and, XIII:114-115 (See also EVOLVE) relationship to megaesophagus, 489 Gastric emptying assessment of, XIII:611-612, XIII:611t effect of erythromycin on, XIII:616 prokinetic agents for, XIII:614-617 (See also EVOLVE) Gastric ischemia, from GDV, 77 Gastric necrosis, 81-82 with gastric dilatation-volvulus, XIII:167-168 Gastric neoplasia, XIII:622-623 Gastric prokinetic agents, XIII:614-617. See also EVOLVE Gastric secretions, 497-498, 498f Gastric ulceration causes of, 498-499, 499f causing protein-losing enteropathy, 513 diagnosis and treatment of, 497-501 gastrinoma and, XIII:617 with renal failure, 877, 914 Gastrin levels in kidney failure, 914 measurement of, XIII:618-619 Gastrinoma, XIII:617-621, XIII:618t, XIII:620t. See also EVOLVE Gastritis chronic and Helicobacter-associated disease, 492-497, 494f, 495f, 495t from renal failure, 877, 914 Gastrocentesis, 80 Gastroenteritis, from uremia, XIII:865 Gastroesophageal reflux esophagitis and, 482-486, XIII:607-608 from feeding tubes, 590 therapy of, XIII:616 Gastrografin. See Diatrizoate meglumine Gastrointestinal disorder(s) differential diagnosis of, with acute abdomen, 68t from chemotherapy, 308 from chronic kidney disease, 873t, 877, 914, 916 from pythiosis, 1268 ulceration, gastrinoma and, XIII:617 Gastrointestinal motility, assessment of, XIII:611-614, XIII:611t, XIII:612t. See also EVOLVE Gastrointestinal neoplasia, XIII:622-624 Gastrointestinal protectants, for shock, 7 Gastrointestinal, protein loss, XIII:641-643 Gastropexy, 80-81 Gastroscopy, 500 Gastrostomy tube feeding for chronic kidney disease, 873t placement and complications of, 907-908 Gastrostomy tube(s), XIII:71t, XIII:72, XIII:72t. See also Percutaneous gastrostomy (PEG) tube

Gastrotomy, after polyurethane glue ingestion, 140 Gelatins, XIII:67t, XIII:68 Gelofusine (Succinylated gelatin), XIII:67t Gemcitabine (Gemzar), 312t, 314 Gene delivery, methods of, XIII:496-497 Gene therapy, for cancer, XIII:493-497, XIII:494t Genetic causes of pregnancy loss, 988 diseases in cats, 1045 disorders of the reproductive tract, 1034-1040 Genetic disease(s). See under Congenital disease(s) Genetic immunotherapy, XIII:494 Genetic linkage tests, 1058, 1058f, 1059t Genetic test(s) for canine hereditary disorders, 1054-1059, 1056t, 1057t for syringomyelia and Chiari-like malformation, 1107-1108 labs offering, 1055t Genital papilloma, canine, XIII:570 Genitalia development, effect of early neutering on, 1021 Gentamicin (Gentocin) adverse reactions of, in dogs, XIII:240t aerosolization of, 644, 662 drug monitoring of, XIII:28t for Bordetella spp. bronchial infections, 644 for Pseudomonas spp., 435t, XIII:264 for sepsis, XIII:273t intravitreal, 1148t, 1212 minimum inhibitory concentrations of, XIII:35t otic, 431t subconjunctival, 1147t toxicity of, 162, XIII:214 Gentocin. See Gentamicin (Gentocin) Geriatric screen testing, 885b Geriatric(s) hyperthyroidism in, diagnosis of, XIII:338 vaccine recommendation with, XIII:255-256 German shepherd dog(s) and hypopituitary dwarfism, XIII:376 avermectin toxicosis in, 125-127 gracilis-semitendinosus myopathy in, XIII:989-992 hepatic fibrosis in, XIII:678 infective endocarditis in, 787 metatarsal fistulation of, 423 predisposition to leptospirosis, 1237 renal cystadenocarcinoma in, 928 ventricular arrhythmias in, 728-729 von Willebrand’s disease in, XIII:434 German shorthaired pointer(s), von Willebrand’s disease in, XIII:434 German wirehaired pointer(s), von Willebrand’s disease in, XIII:434 Gestation, normal, 992 Giardiasis compared to tritrichomonas, 510 diagnosis of, using ELISA, XIII:11 vaccine recommendations for, 1274, 1277 Gingival hyperplasia, from cyclosporine, 387 Gingivostomatitis, feline, 476 Glanzmann’s thrombasthenia, genetic tests for, 1056t Glargine, use in cats, 201-202, 202b Glasgow coma scale, 34 Glaucoma, XIII:1044-1045 canine, XIII:1075-1081, XIII:1078t corneal edema from, 1160f feline, 1207-1214, 1208b mydriasis from, 1171 red eye from, 1178 secondary, from uveitis, 1205, 1207 treatment of, XIII:1092-1093 Glimepiride, XIII:351, XIII:351t Glioma, 1080 Glipizide (Glucotrol), XIII:351, XIII:351t clinical effects of, XIII:352f use of, in cats, 204 Globoid cell leukodystrophy, autosomal recessive inheritance of, XIII:910t

Glomerular disease, 863-867 Glomerular filtration rate effect of hyperthyroidism on, XIII:337-338 in polyuria and polydipsia, 849 measuring of, 868-871, 871b Glomerulonephritis, 863-865 canine, XIII:851-853, XIII:852t secondary, 929 Glomerulonephropathy cutaneous and renal, of greyhounds, XIII:854-855 (See also EVOLVE) diagnosis of, urine collection for, XIII:13t Glomerulosclerosis, 867 Glucagon for passage of urinary calculi, 933 shock and, 7 Glucocorticoid(s). See also Cortisol; Dexamethasone; Prednisone adverse effects of, 403-405, 568t causing gastric ulceration, 498-500 aerosol delivery of, 656-657 anti-inflammatory effect of, 403b as immunosuppressive agents, 255, 402, XIII:510 associated with pancreatitis, XIII:698 comparison of, 401t contraindications for the use of, 403-405 effect of on ACTH stimulation test, 170, XIII:321 on liver, 545, 549-553, 568t, XIII:670 on thyroid function, 187t for abortion, XIII:953 for acral lick dermatitis, 471 for anaphylaxis, 419 for anterior uveitis, 1205, 1206t for atopic disease, in cats, XIII:567 for autoimmune myasthenia gravis, 1109 for chronic bronchitis, 643-644, XIII:802-803 for chronic colitis, 519, 519t, XIII:647-648 for cough due to tracheal collapse, XIII:800 for craniocerebral trauma, XIII:181t, XIII:183-184 for episcleritis, in dogs, 1191t, 1192 for esophageal disease, 485 for eye diseases, 1146-1147, 1147t, 1150-1151, 1150t, 1257 for feline asthma, 654, XIII:808 for feline calicivirus, 1286-1287 for feline chronic bronchitis, 654 for feline idiopathic cystitis, 948 for feline infectious peritonitis, 1296, 1296b for feline inflammatory liver disease, 579 for feline lower urinary tract disease, XIII:892 for feline pruritus, 407-408, XIII:543 for feline rhinitis, 618 for gastric dilatation-volvulus, 79, XIII:166-167 for hepatic lipidosis, 575 for hypercalcemia, 346-347, 346f in cats, 238-239 for hypoadrenocorticism, 233-235 for immune-mediated hemolytic anemia, 269-270, XIII:431-432 for inflammatory bowel disease, 505 for interstitial lung disease, 674 for intracranial tumors, 1079t for mast cell tumors, 376, 377b for mycoplasmosis, 1248 for neurologic and musculoskeletal pain, 1128-1129, 1128t for ocular disease, 1150-1151, 1150t for otitis externa, XIII:585-586, XIII:585t and media, 434 from Pseudomonas, XIII:587, XIII:587t for protein-losing enteropathy, 514 for pyotraumatic dermatitis, 448 for shock, 8, 229, XIII:145 for spinal cord disease, XIII:188 for thrombocytopenia, 286, XIII:440 for tracheal collapse, 634 for traumatic brain injury, 36 in shampoos, 411t, 412 intralesional injection, for acral lick dermatitis lesions, 472 role of, 400-401

Glucocorticoid(s) (Continued ) subconjunctival, 1146, 1147t topical, potency of, XIII:585t use of, 400-405 with infectious disease, 1230-1233, 1232t, 1233t vaccine recommendation and, XIII:254-255 Glucosamine chondroitin, for hip dysplasia, 1123 Glucosamine hydrochloride, for feline ­idiopathic cystitis, 947t, 949 Glucose. See also Blood glucose; Diabetes ­mellitus; Hyperglycemia; Hypoglycemia evaluation of, in cats in critical care, XIII:100 for shock, XIII:145 in abdominal fluid, 71 intolerance to, in parenteral nutrition, XIII:88-89 maintenance of, in cats in critical care, XIII:100 parenteral solutions of, XIII:80t Glucose curve, XIII:349-350 for canine diabetes mellitus, 197-198 for feline diabetes mellitus, 199-203, 201-203, 202b Glucose-6-phosphate dehydrogenase (G6PD) deficiency, XIII:416t Glucotoxicity, 200 Glutamine, in critical care, XIII:203 Glutamyl transferase (GGT) abnormalities in, 544-546, 552 in drug-associated liver disease, 567-568 in feline inflammatory liver disease, 577-581 Glutathione for liver toxicity, 569 system, XIII:481 Gluten, dietary, XIII:654 Glycated hemoglobin, 210 Glycemic index, 206 Glycerin products, as tear substitutes, XIII:1064t Glycoflex, for osteoarthritis, XIII:1021 Glycoprotein IIb/IIIa antagonist(s), as antiplatelet therapy, 25 Glycopyrrolate, XIII:125t Glycosaminoglycan(s), for feline lower urinary tract disease, 945b, 947t, 949, XIII:892-893 Glycosuria, primary renal, 846t Glycosylated hemoglobin, for monitoring diabetes mellitus, XIII:349 Goal directed therapy, for shock, 7-8 Gold salts causing nephrotoxicity, 160b in dermatology, XIII:537 Golden retriever, syncope in, 710 Golf balls, 127 Gonadal sex, 1034-1035, 1036t, XIII:904-906, XIII:905t Gonadectomy early age, 1019-1024 for estrus suppression, 1025 Gonadotropin-releasing hormone (GnRH) adverse effects of, 1029 for diagnosis of feline ovarian remnant syndrome, 1040 for estrus suppression, 1025, 1029 for urinary incontinence, 957t, 958 Gonazon CR, 1029 Gonio-implant, 1212 Gonioscopy, 1145, XIII:1076 Gorilla glue toxicity, 140 Gotch ear, vector associated with, XIII:297t Gracilis-semitendinosus myopathy, XIII:989-992 Granular cell myoblastoma, of larynx, XIII:503t Granulocyte colony-stimulating factor (G-CSF), XIII:404-405 for canine parvovirus infection, XIII:631 for feline immunodeficiency virus, 1280 for neutropenia from chemotherapy, 307-308 Granulocyte-macrophage colony-stimulating factor, XIII:405-406

  Index Granulocyte-monocyte colony-stimulating factor, XIII:405f Granulocytic anaplasmosis, 1250, 1250f Granuloma, palisading, 464 Granulomatous colitis, 516, 521-523 Granulomatous episclerokeratitis, nodular, XIII:1069-1070 Granulomatous laryngitis, 629 Granulomatous meningoencephalomyelitis (GME), 1070-1071, 1073 causing retinal detachment, 1216 Granulomatous skin nodules, 462-465, 462b Grape and raison toxicity, 109, 856b diagnosis and treatment of, 142-143 Grass, toxicity of, XIII:220-221t Great Dane dog(s), cervical spondylomyelopathy in, 1088-1093 Green-lipped mussel supplements, for hip dysplasia, 1123 Greenetrack disease. See under Glomerulonephropathy Greenies ingestion, 111 Greyhound(s), cutaneous and renal glomerulopathy of, XIII:854-855 See also EVOLVE Griseofulvin adverse reactions of, in cats, XIII:241t for dermatophytosis, 460, 461t, XIII:579 Growth hormone deficiency of, causing immunodeficiency, XIII:519 dosage of, XIII:377 for dermatosis in adult dogs, XIII:376-377 for pituitary dwarfism, XIII:376 preparations of, XIII:377 use of, in dogs, XIII:376-377 (See also EVOLVE) Growth, effect of early neutering on, 1019-1024 Guarana toxicity, 151-152 Guaranteed analysis, XIII:74-75 Gum toxicity, 139-140 H H2 blocker(s) for acute renal failure, 881 for chronic kidney disease, 873t, 877, 916 for esophageal disease, 484, XIII:609 for gastric ulceration, 500 for vomiting cats, 574-575 toxicity of, XIII:229 Habitrol ingestion, 136, 136t Haemaccel (Urea-linked gelatin), XIII:67t Haemobartonellosis. See Mycoplasmosis Haemophilus influenzae, resistance of, XIII:262 Half-life, dosing interval and, XIII:27-31 Halothane, associated liver disease, 568t Head trauma diagnosis and treatment of, 33-37, 35t vestibular signs from, XIII:970 Hearing loss. See Deafness Heart block. See Atrioventricular (heart) block Heart disease. See also Congenital disease(s); Heart failure; specific disorders arrhythmias and (See Arrhythmia(s)) arrhythmogenic right ventricular cardiomyopathy, 797-799 arterial thromboembolism from, 819-824, 820f, 820t, 821f, 822f, 822t as complications of thyroid disease, XIII:716-719 (See also EVOLVE) associated with hypothyroidism, XIII:328 asymptomatic, 776 boxer cardiomyopathy, 797-799 cardiomyopathy in Doberman pinschers, 800-803, 801f causing pulmonary hypertension, 702 computed tomography for, XIII:709-710 (See also EVOLVE) congenital, feline, XIII:738-741, XIII:740t (See also EVOLVE) dilated cardiomyopathy, in dogs, 792-797 feeding strategies for, XIII:715 feline myocardial disease, 809-815 from heartworms (See Heartworm disease) functional classification of, 770-771

1361

Heart disease (Continued ) infective endocarditis, 786-791, 788t, 790b low-sodium treats for, 705t mitral valve dysplasia, 765-768 myocarditis, 804-808 natriuretic peptides in, 783 nutritional management of, 704-708, 773, XIII:711-716 obesity and, XIII:711-712 patent ductus arteriosus, 744-747 pericardial effusion, 825-831 pulmonic stenosis, 752-756 responses to dysfunction of, XIII:748-749 right ventricular cardiomyopathy, in cats, 815-818 screening for, 770-772 subaortic stenosis, 757-761 surgical indications for, XIII:747-748 syncope in, 709-712, 710b tricuspid valve dysplasia, 762-765 valvular heart disease, in dogs, 780-786 ventricular septal defect, 748-751 Heart failure. See also Valvular heart disease; specific disorder e.g. Cardiomyopathy and dental disease, 778 and hyperadrenocorticism treatment, 234 arrhythmias in, 775, 777-778 as a complication of thyroid disease, XIII:716-719 (See also EVOLVE) balance of minerals and electrolytes with, XIII:713-714 cachexia from, XIII:711 causes and classification of, 770-771 causing pulmonary hypertension, 698-700, 698b, 700f causing syncope, 711t, 712t, 719-711 chronic diet and exercise considerations for, XIII:749-750 outpatient management of, XIII:748-752 complications of, treatment of, XIII:749t control of, with tracheal collapse, 631f, 633 definition of, 769 diagnosis and treatment of, 769-780, 777f, 779t feline with congenital heart disease, XIII:741 with myocardial disease recurrent, XIII:765 treatment of, XIII:765-766 from canine heartworm disease, 839 from infective endocarditis, 787, 791 from valvular heart disease, 781-785 from ventricular septal defect, 748 hyperkalemia and hyponatremia with, XIII:375 nutritional management of, 705-707, 779t, 784, 796 pericardial effusion and, management of, XIII:775-776 prognosis for, 779-780 progression of, XIII:752-753 refractory, XIII:749t, XIII:752-756 right-sided, effect of, on liver, XIII:668t shock and, treatment of, XIII:143 therapy of omega-3 fatty acids for, XIII:714-715 sodium nitroprusside for, XIII:194-197 (See also EVOLVE) sodium restriction for, XIII:713-714 transvenous pacing and, XIII:198 Heart murmur(s) arrhythmogenic right ventricular cardiomyopathy, in cats, 816 asymptomatic cat with, 809-810 dog with, 781, 783 with congenital heart disease, in cats, XIII:738, XIII:739t with dilated cardiomyopathy, in dogs, 792 with hypertension, 714t with infective endocarditis, 787 with mitral regurgitation, 772 with mitral valve dysplasia, 766

1362

  Index

Heart murmur(s) (Continued ) with patent ductus arteriosus, 744 with pulmonary hypertension, 699 with pulmonic stenosis, 752 with subaortic stenosis, 758-760 with tricuspid valve dysplasia, 762 with valvular heart disease, 781 with ventricular septal defect, 748-749 Heart-based tumor, 826 Heartworm disease canine diagnosis and treatment of, 837-842, 838t, 840f during pregnancy, XIII:932 occult infection of, XIII:777 prevention of, 390-394, 842, XIII:777-782, XIII:781f role of Wokbachia in, 841 causing pulmonary hypertension, 698, 698b diagnosis of antigen concentration for, XIII:788 thrombocytopenia from, XIII:440, XIII:441t using ELISA testing, XIII:11 feline, XIII:783f arrhythmias with, 732 diagnosis and treatment of, 831-837, 832f, 834f prevention of, 835, XIII:782-787 prognosis for, 836 prevention of, avermectins for, 390-394 thrombocytopenia from, 283t Heat ablation, for hyperparathyroidism, 250 Heat therapy, for hip dysplasia, 1124 Heat trauma, XIII:178-186 Heet liniment, for acral lick dermatitis lesions, 472 Heinz body(ies). See also under Anemia on erythrocyte scattergrams and histograms, XIII:383 quantitation of, XIII:422 Helicobacter spp. associated gastric disease, 492-497, 494f, 495f infectious disease emergence of, XIII:245 treatment protocols, for dogs, 495t role of, in feline inflammatory liver disease, 576, 578, 580 Heliotropium europaeum, 151t Helminths, neonatal diarrhea from, XIII:627t Hemangiosarcoma. See also Neoplasia; Radiation therapy; Sarcoma cardiac, 356 pericardial effusion from, 826, XIII:773 clinical staging system for, 328b diagnosis and treatment of, 328-331, 329b, 329f nasal and paranasal, XIII:501t splenic, XIII:521-522 Hematocrit, abnormalities of, XIII:105t Hematology abnormalities of, differential diagnosis in, XIII:105t blood smear in, importance of, XIII:394 buffy coat analyzer of, XIII:395 cytograms and histograms for, XIII:381 methodologies for, XIII:391 quality control products for, XIII:391-392 Hematology instrumentation, for in-house ­laboratory, XIII:391-396, XIII:392t, XIII:394t Hematoma, splenic, XIII:522 Hematopoietic cells, maturation of, XIII:404f Hematopoietic cytokines, XIII:403-414, XIII:408-414. See also EVOLVE Hematuria with feline urethral obstruction, 953-954 with renal nephrotomy, XIII:867 work up with feline, 944, 946t Hemlock, 151t Hemoabdomen, 71, XIII:163

Hemodialysis complications of, 899 facilities that offer, 900b for acute renal failure, XIII:177 for ethylene glycol toxicosis, 132, 161, XIII:214 for ureteroliths azotemia, 933 indications for, 897b, 898 pathway of blood with, 897f principles and protocols for, 896-900 Hemodynamic monitoring, Swan-Ganz catheters, 3-4 Hemoglobin and oxygen saturation, 596 carbamylated, renal failure and, XIII:858 glycosylated (See glycosylated hemoglobin) hereditary disorders of, XIII:415-419 levels requiring oxygen therapy, 598 oxyglobin as substitute for, XIII:424-427 Hemoglobin-based oxygen carriers, 64 Hemoglobinopathies, XIII:416t Hemolysis. See Anemia, hemolytic specific condition e.g. Mycoplasmosis Hemolytic anemia. See Anemia, hemolytic Hemophagocytic syndrome, 274-275 Hemophilia A, 279, XIII:436 Hemophilia B diagnosis and treatment of, 279, XIII:436 genetic test for, 1056t X-linked inheritance of, XIII:910t Hemoplasmas, diagnosis and treatment of, 1245-1248 Hemorrhage associated with disseminated intravascular coagulation, 287-291 causing stroke, 1075-1077 colloid use for, XIII:133t, XIII:135 gastrointestinal, from renal failure, 914 postpartum, 999 Hemostasis disseminated intravascular coagulation and, XIII:190 transfusion to maintain, XIII:402 Hemothorax, 675 Heparin as anticoagulant therapy, 25-27, 26f, 27f changing to warfarin with, 696 dosage of, in cats, XIII:102 for disseminated intravascular coagulation, 291, XIII:145-146, XIII:193-194 for gastric dilatation-volvulus, 81-82 for immune-mediated hemolytic anemia, 271 for prevention of thrombi, 693-696 for thromboembolism, 814, 823, XIII: 766-767 in pleural space lavage, 677 low-molecular weight, 693-694, 696, 824 unfractionated, 693, 696, 823 weight-based nomogram of, 694t Hepatic disease. See also under Liver poikilocytosis and, in cats, XIII:423 with diabetes mellitus, 215 Hepatic encephalopathy from portosystemic shunts, 582 nutritional management of, XIII:696 treatment of, 571, 579 Hepatic failure effect on thyroid function, 187 from leptospirosis, 1237-1240 Hepatic fibrosis, in dogs, XIII:677-681, XIII:677t, XIII:678t, XIII:680t Hepatic lipidosis diagnosis and treatment of, 570-575, XIII:686-690 features of, XIII:673t hypokalemia and, XIII:695 nutritional management of, XIII:696-697, XIII:696t pancreatitis and, in cats, XIII:702 ursodeoxycholic acid therapy for, 565 with diabetes mellitus, 215 with pancreatitis, 539 Hepatic nodular hyperplasia, XIII:675-676, XIII:675t

Hepatic reaction, XIII:668 Hepatic support therapy, 554-557 Hepatitis chronic nodular hyperplasia and, XIII:670-671 copper-associated, 557-562, 559b, 560f from cholangitis, in cats, 576-581 lymphocytic portal, 580-581, XIII:673t in cats, XIII:672-673 reactive, XIII:668-669 ursodeoxycholic acid therapy for, 563-565 X, 156-159 Hepatobiliary disease breeds predisposed to, 545b clinical findings of, XIII:659t diagnostic approach to, 543-549, XIII: 659-664, XIII:662f, XIII:663f differential diagnosis of, for acute abdomen, 68t extrahepatic enzyme elevation with, 544b hepatic fibrosis in, XIII:677-681 laboratory evaluation of, 544-547 ursodeoxycholic acid for, 563-565, XIII: 691-693 (See also EVOLVE) Hepatocutaneous disease, 1181 Hepatoportal microvascular dysplasia, XIII: 682-686 See also EVOLVE Hepatotoxicity agents associated with, 544b, XIII:218t diagnosis and treatment of, XIII:217-219 essentials facts of, XIII:219t from aflatoxin, 156-159 from chemotherapy drugs, 309 from methimazole, 177 Hepatozoonosis diagnosis and treatment of, in dogs, XIII:310-313 (See also EVOLVE) prevention of, XIII:312 vector associated with, XIII:296t Herbal intoxications, 149-156, 154t Herbal product toxicity, 110, 149-156, 154t Herbicide(s) causing nephrotoxicity, 160b exposure to, 93 toxicity of, XIII:221-222, XIII:222t Hereditary disorder(s) breeds associated with deafness, XIII:972-973 coagulopathies, 277-280, XIII:434-438 immunodeficiency diseases as, XIII:516-520 (See also EVOLVE) neutrophil dysfunction, XIII:448-450 of erythrocytes, XIII:415-419, XIII:416t (See also EVOLVE) platelet function defects, 295, 295t tests for canine, 1054-1059, 1055f, 1055t, 1056t, 1057t Hermaphrodite, 1035-1037 Hernia, inguinoscrotal, XIII:945 Herpesvirus canine causing pregnancy loss, 987 during pregnancy, XIII:932-933 thrombocytopenia from, 282t, XIII:440 feline antiviral drugs for, 1188-1190 causing blepharitis, 1180 causing conjunctivitis, 1177, XIII:276, XIII:1044 control of, in catteries, 1300t, 1301 cutaneous lesions from, 424, 441 interferons for, 390 ocular, XIII:1057-1060, XIII:1074 (See also EVOLVE) polymerase chain reaction for, XIII:248 rhinitis, 617-618 vaccination for, 1275, 1276t keratitis from, XIII:1074 thrombocytopenia from, XIII:441t vaccination recommendations for, XIII:250 Hetastarch, 64-66, 65t characteristics of, 63t colloid therapy using, XIII:67-68 use of, XIII:67t, XIII:133t, XIII:134 in cats, XIII:100 in disseminated intravascular coagulation, XIII:193

Hetastarch (Continued ) use of (Continued ) in gastric dilatation-volvulus, 78 in sepsis, XIII:273 in shock, XIII:142 Heteroresistance, 450 Hiatal hernia, 483-484, XIII:608 High-dose dexamethasone suppression test, adrenal mass and, XIII:370 High-potassium erythrocytes, XIII:417t Hill’s Science Diet m/d, 208t Hip dysplasia medical treatment of, 1120-1125, 1124t screening methods for, 1121-1122 Hippuric acid crystalluria, 851t Hirsutism, from cyclosporine, 387 Histamine, action of, XIII:48-49 Histiocytic disease complex, 348-351 Histiocytic diseases cutaneous, XIII:588-591 fibrohistiocytic nodules, 464 histiocytoma(s), from vaccination, in cats, XIII:498-500 immunophenotyping for, XIII:508 nonneoplastic nodular, 462-465 sarcoma, 350-351, XIII:590-591 immunophenotyping for, XIII:508 ulcerative colitis, 502, 505, 521-523, XIII:645 Histiocytoma(s), canine cutaneous, 348-349 Histochemical grading for copper, 559b Histograms, interpretation of, XIII:381-390 Histology for food allergy, XIII:636t liver, for hepatoportal microvascular dysplasia, XIII:684-685, XIII:684f Histone deacetylase (HDAC), for hemangiosarcoma, 331 Histopathology and staging of mammary tumors, 364t, 365t, 367t classification of inflammatory liver disease, 576, 577b for lagenidiosis, 1270-1271 of excised tumors, 323 of feline gastrointestinal lymphoma, 340-341 of feline inflammatory liver disease, 576-581 of feline right ventricular cardiomyopathy, 817, 817f of feline viral skin disease, 441-443 of Helicobacter spp., 494-495, 495f of inflammatory bowel disease, 503 of kidney for glomerular disease, 864 of pythiosis, 1268-1269 of tritrichomonas, 510-511 of ulcerative colitis, 521, 522f Histoplasmosis diagnosis and treatment of, 1265-1267, 1266t, 1267t intestinal, protein-losing enteropathy and, XIII:642 ocular signs of, XIII:279 respiratory tract, XIII:815-818, XIII:816f thrombocytopenia from, 283t, XIII:441t Holter monitoring for boxer cardiomyopathy, 798 for Doberman pinscher cardiomyopathy, 800-803 for monitoring treatment of ventricular arrhythmias, 730 for occult cardiomyopathy, XIII:757 for screening dogs at risk of heart disease, 772 to detect cause for syncope, 711 Home, toxicity of products in, XIII:223-226 Home-cooked diets, for food allergies, 396 Homemade pet foods, 166-167 Hopeanine toxicity, 141 Hordeolum, 1179, XIII:1051 Hormone(s) as chemotherapy, XIII:471 for mammary cancer, 365-366 Horner’s syndrome and anisocoria, XIII:1050 as complication of feline respiratory tract polyps surgery, XIII:795-796 from nasopharyngeal disorders, 622, 625

  Index Horse chestnut, 151t Horseradish essential oil, 152t Hospital-acquired bacterial infections, 1222-1225 Hot spots. See Pyotraumatic dermatitis (hot spots) Hotz-Celsus procedure, XIII:1055 House dust allergy, control of mites for, 425-427 Household chemicals nontoxic, XIII:226 toxicity of, XIII:223-227 incidence of, XIII:206t Household products, causing nephrotoxicity, 160b Human albumin, 265 Human drug ingestion, 92-99, 97t toxicity, 144-146 Human food toxicity, 167 Human gamma globulin, for thrombocytopenia, 286t Human hormone replacement ingestion, 148t-149t Human immunodeficiency virus, infectious disease emergence and, XIII:244-245 Human interferon-alpha, for feline retrovirus, 1281t, 1283 Human serum albumin solution characteristics of, 63t for resuscitation, 65t for shock, 5-6 Humectant(s), 132 for sebaceous adenitis, 452 Humeral immunity, of Bartonella spp. infections, XIII:306 Humerus condylar fractures of, and incomplete ossification, in dogs, XIII:1000-1004 osteochondritis dissecans, XIII:1006-1014 Humidification, effect on airway management, XIII:791 Humidifier(s), XIII:791 Husbandry, and feline leukemia virus, XIII:283 Hyaluronic acid (HA), XIII:1021 Hybridization, in situ, XIII:246 Hydralazine for heart failure, 776 for refractory heart failure, XIII:753-754 Hydration. See also Fluid therapy effect on airway management, XIII:790-791 with kidney disease, 874t, 876-877, 891 Hydraulic fluid, 132 Hydrocarbon toxicity, 134 Hydrochlorothiazide adverse effects of, 774 for dilated cardiomyopathy, in dogs, 793-794 for feline cardiomyopathy, 811t, 814, 818 for feline urinary tract disease, XIII:889t for heart failure, 772-774, 784 for refractory heart failure, XIII:755 Hydrocodone for acral lick dermatitis, 473, XIII:555 for cough, 634, 645 Hydrocortisone. See also Cortisol; Glucocorticoid(s) comparison of, to other glucocorticoids, 401t for ocular diseases, 1150, 1150t topical for hot spots, 448 otic, 432, 432t use of, with infectious diseases, 1232-1233, 1232t, 1233t Hydrogen breath test, XIII:639-640 Hydrogen peroxide as antiseptic, XIII:261 use in toxicities, 96, 97f, 113t Hydrolyzed protein diets, 395-396, 396t, 518 Hydrometra, in cats, XIII:930 Hydromorphone for neurologic and musculoskeletal pain, 1128t for pain management, 11-12, 11t use of, with gastric dilatation-volvulus, 80

1363

Hydronephrosis, nephrotomy and, XIII:867 Hydroxyamphetamine, for evaluating anisocoria, 1174 Hydroxyethyl starch. See Hetastarch; ­Pentastarch Hydroxyprogesterone, role of in hyperadrenocorticism, 221, 222t in nonadrenal illness, 221 Hydroxyurea as chemotherapy, XIII:468 for intracranial tumors, 1079t, 1081 for polycythemia, 751 Hydroxyzine HCl, for feline pruritus, 408 Hygiene, for viral disease control, 1300-1301 Hymen, imperforate, 1016 Hymenoptera sting(s). See Bite(s) Hyoscyamus niger, 151t Hyoscyamine sulfate, for syncope, 712t Hyperadrenocorticism (Cushing’s disease) adrenal, 227, XIII:369 atypical and subclinical, 219-224 causing hypertension, 713-714, 714t clinical signs of, 219 diagnosis of, 219-223, 219-224 cortisol:creatinine ratios for, XIII:322 dexamethasone suppression test, XIII:321-322 interpretation of tests for, 170-172 pituitary vs. adrenal, 171-172, 220-221, XIII:322 effect of on liver, XIII:668t, XIII:670-19 on thyroid function, 187 feline, dexamethasone suppression test for, XIII:321-322 in ferrets, XIII:372-374 monitoring therapy of, 171, XIII:321 myopathy and myotonia from, 1114 neuropathy from, 1115 nodular hyperplasia and, XIII:670-671 nonadrenal disease effects on, XIII:362-363 pituitary large pituitary tumors and, XIII:366-368 (See also EVOLVE) treatment of, 224-227, XIII:364-366 polyuria and polydipsia in, 845, 847t, 848-849 risk for pulmonary thromboembolism, 696 treatment of, 223, 224-227 urinary tract infection associated with, XIII:878-880 vaccine recommendation and, XIII:255 Hyperalbuminemia, acid-base disorders and, 58b Hyperaldosteronism and hypertension, 714t, 716 polyuria and polydipsia from, 847t Hyperalimentation, neutrophil dysfunction in, XIII:449t Hyperbaric oxygen therapy, 601-602, 602b Hyperbilirubinemia, 546 differential diagnosis of, XIII:109t extrahepatic disease and, XIII:669-670 from hepatic lipidosis, 571 from immune-mediated hemolytic anemia, 268 Hypercalcemia canine, and primary hyperparathyroidism, 247-251 causing pancreatitis, XIII:698 differential diagnosis of, 237b, 247-248, 345, XIII:346 feline idiopathic, 236-241, 238f, 239f, 240f formula for corrected calcium, 345 iatrogenic, 246, XIII:344 nephrosis from, 346 paraneoplastic, 343-347, 346f polyuria and polydipsia in, 847t, 848 treatment of, XIII:347-348 with azotemia, 858, 929-930 Hypercapnia, 57-58 causes of, 604 Hyperchloremic acidosis, 60, 60b Hypercholesterolemia differential diagnosis of, XIII:109t from hypothyroidism, XIII:328

1364

  Index

Hypercoagulability, 690 diagnosis and treatment of, 24-28 testing for, 692 Hypercoagulation, 288-289 Hyperglobulinemia from leptospirosis, XIII:309 in feline infectious peritonitis, XIII:291 Hyperglycemia. See also Diabetes mellitus control of, in traumatic brain injury, 36 differential diagnosis of, XIII:109t during pregnancy, in dogs, XIII:932 in canine diabetes mellitus, 195-199 in feline diabetes mellitus, 199-204 role of, with cerebrovascular disease, 1077 Hyperinsulinemia, from insulinoma, XIII:357-361 Hyperkalemia acute renal failure and, XIII:175 arrhythmias from, 735, 735f causing bradyarrhythmias, XIII:722 differential diagnosis of, XIII:106t, XIII: 374-376, XIII:375t (See also EVOLVE) with hyponatremia, XIII:374-376 (See also EVOLVE) from ACE inhibitors and renal insufficiency, XIII:712-713 from acute renal failure, 881, XIII:176t from feline urethral obstruction, 951-952 from hypoadrenocorticism, 233 treatment of, in cats, XIII:100 Hyperlactatemia, XIII:112-116, XIII:114t. See also EVOLVE Hyperlipidemia causing aqueous opacification, 1165 corneal disease from, 1161, 1161f from hypothyroidism, XIII:328 ocular changes associated with hypothyroidism and, XIII:328 Hypernatremia differential diagnosis of, XIII:106t from paintball ingestion, 141-142 Hyperparathyroidism and canine hypercalcemia, 247-251 with chronic kidney disease, 889t, 890t, 893-895, 893f Hyperphosphatemia acid-base disorders and, 58b, 59 differential diagnosis of, XIII:107t from chronic kidney disease, 873t, 875-876, 889t, 890t, 893f from hypoparathyroidism, 241, 243 Hyperproteinemia. See Hyperglobulinemia Hypersensitivity. See also Allergy(ies); Drug toxicity to drugs, causing cutaneous reactions, XIII:556-559 Hypersthenuria, 848 Hypertension causes of, XIII:1082 causing retinal detachment, 1216, 1217f diagnostic tests recommended for patients with, 715b dietary recommendations for, XIII:846 in cats, XIII:843t in dogs, XIII:846t emergency management of, XIII:840 from erythropoietin therapy, 917 from pheochromocytoma, XIII:371 in cats, XIII:101 intracranial, with tumors, 1079, 1082 progressive renal failure and, XIII:863 pulmonary (See Pulmonary hypertension) renal injury from, 713 retinopathy from, XIII:1082-1085 (See also EVOLVE) sodium nitroprusside for, XIII:196 systemic, 713-717 with acute renal failure, 882 with chronic kidney disease, 874t, 878, 885-886, 888f, 888t managing, 891, 891t with diabetes mellitus, 214 with feline arrhythmias, 733 with hyperthyroidism, 176t, 178-179, XIII:717 with renal disease, 910-913 with stroke, 1076

Hyperthermia causing myocarditis, 805t for cancer therapy, XIII:486-494 Hyperthyroidism arrhythmias with, 731 causing pregnancy loss, in queens, 1044 complications of, cardiovascular, XIII:717 diagnosis of, interpretation of tests for, 173 effect of, on liver, XIII:668t, XIII:670 Heinz body formation in, XIII:422 hypertension and, 713, 714t iatrogenic hypothyroidism and, XIII:339 myopathy from, 1114 polyuria and polydipsia in, 844-847, 847t renal failure and, XIII:336, XIII:337-339 (See also EVOLVE) risk of arterial thromboembolism with, 820, 821f therapy of advantages and disadvantages of, 176t, 180-181 medical, 175-179, 176t, XIII:333-337 adverse effects from, XIII:335t monitoring of, XIII:335 presurgery, XIII:336 trial, XIII:336 with radioiodine, 180-184 Hypertonic saline for craniocerebral trauma, XIII:181t for shock therapy, 5 for traumatic brain injury, 35, 35t Hypertonic solutions, for shock therapy, 5 Hypertriglyceridemia, causing aqueous opacification, 1165 Hypertrophic cardiomyopathy. See under Cardiomyopathy Hypertrophic osteoarthropathy (HO), and megaesophagus, 492 Hyperviscosity, causing retinal detachment, 1216 Hyphema, 1178, XIII:1044 associated with feline glaucoma, 1213 causing blindness, 1165 from anterior chamber paracentesis, 1202 Hypoadrenocorticism (Addison’s disease) causing azotemia, 856b, 857 causing syncope, 710b clinical findings in, 232t diagnosis and treatment of, 231-235 diagnosis of, XIII:374 electrolyte abnormalities in, XIII:374 interpretation of tests for, 170-172, XIII:321 laboratory findings in, 232t effect of on liver, XIII:668t on thyroid function, 187 megaesophagus and, 488, XIII:603-604, XIII:605 polyuria and polydipsia from, 847t with concurrent hypothyroidism, XIII:329 Hypoalbuminemia anorexia and, XIII:71 from hepatobiliary disease, 546, XIII:660 from protein-losing enteropathy, 512-515 therapy for, 5-6 Hypoalbuminemic alkalosis, 58-59, 58b Hypoallergenic diets, 395-397, XIII:530-536. See also EVOLVE Hypocalcemia clinical signs of, 243b, XIII:341t differential diagnosis for, 242b, XIII:107t, XIII:340t during dystocia, in dogs, XIII:935 from hypoparathyroidism, 241-247, XIII:340 from puerperal tetany, 1001-1002, 1004 postoperative, in cats, XIII:341 therapy of with oral calcium salts, XIII:343t with parenteral calcium, XIII:342t with vitamin D compounds, XIII:343t with feline urethral obstruction, 952

Hypocapnia, 57 Hypochloremic alkalosis, 59-60 Hypocholesterolemia differential diagnosis of, XIII:109t from hepatobiliary disease, 546 Hypofibrinogenemia, 279 Hypogammaglobulinemia, transient, of ­infancy, XIII:517-518 Hypoglobulinemia, protein-losing enteropathy causing, 512-515 Hypoglycemia causing syncope, 710, 710b differential diagnosis of, XIII:108t, XIII:358 during pregnancy, in dogs, XIII:932 emergency treatment of, XIII:358-359 from hepatobiliary disease, 546 from xylitol ingestion, 139-140 iatrogenic, from insulin therapy, XIII:354 insulinoma causing, XIII:357-361 (See also EVOLVE) with diabetes mellitus in cats, 203, 208, 215-216 in dogs, 198, 215-216 Hypoglycemic oral agents, 203-204 Hypokalemia arrhythmias and, ventricular, XIII:734 causing myopathy, in cats, 1136-1138, 1137f, 1137t conditions associated with, 1136b in cats, XIII:985t differential diagnosis of, XIII:106t from diuretic therapy and nutrient ­restriction, XIII:712 hepatic lipidosis and, XIII:687 in acute renal failure, XIII:175 in cats, in critical care, XIII:100 in chronic kidney disease, 873t, 876, 889t in gastric dilatation-volvulus, 81 in hepatic lipidosis, 573 liver disease and, XIII:695 parenteral nutrition and, XIII:88 polyuria and polydipsia from, 847t Hypoluteodism, causing pregnancy loss, 988-989 Hypomagnesemia differential diagnosis of, XIII:107t in hepatic lipidosis, 573-574 parenteral nutrition and, XIII:88 ventricular dysrhythmias and, XIII:153 Hyponatremia correction of, in hypoadrenocorticism, 233 differential diagnosis of, XIII:106t, XIII:374-376, XIII:375t (See also EVOLVE) with hyperkalemia, XIII:374-376 (See also EVOLVE) with polyuria and polydipsia, 845, 847t, 849 Hypoparathyroidism complications of, 246-247 diagnosis and treatment of, XIII:340-345 treatment of, 241-247 Hypophosphatemia differential diagnosis of, XIII:107t hepatic lipidosis and, 574, XIII:687 refeeding syndrome and, XIII:87-88 replacement of, in cats, XIII:100 Hypopituitary dwarfism, treatment of, with growth hormone therapy, XIII:376 Hypoplastic trachea, 619 Hypoproteinemia and septic abdomen, 74 from protein-losing enteropathy, 512-515, XIII:641-643 Hypopyon, causing blindness, 1165 Hypospadias, 1038, XIII:907 Hyposthenuria, 848 Hypotension in cats, XIII:101 (See also under Blood pressure) in gastric dilatation-volvulus, XIII:165 therapy of for shock, 4-7 with noncardiogenic pulmonary edema, 665 with feline arrhythmias, 733 with sepsis, XIII:273

Hypothermia craniocerebral trauma and, XIII:184 treatment of, in cats, XIII:105 with arterial thromboembolism, 819 Hypothyroidism canine retrograde ejaculation with, 1051 cardiovascular complications of, XIII:716-719 (See also EVOLVE) causing pregnancy loss, 988 complications and concurrent conditions of, XIII:327-330 (See also EVOLVE) congenital, 186 diagnosis and treatment of, 185-191, 187t, 190f effect of on infertility, in male dog, XIII:940-941 on liver, XIII:668t, XIII:670 iatrogenic, in cats, XIII:339 laryngeal paralysis and, 627-628 megaesophagus and, 488, XIII:604, XIII:605 monitoring therapy for, 172 myopathy from, 1114 neuropathy from, 1115, XIII:974-975 tests for, interpretation of, 172-173, XIII:322-323 treatment of, XIII:330-331 Hypotrichosis, with thymic aplasia, XIII:518 Hypoventilation, 604 Hypovolemia goals with colloid therapy, 65t treatment of, with colloids, 66, XIII:133t, XIII:135 Hypoxemia causes of, 604 causing pulmonary hypertension, 698b, 702 causing syncope, 710, 710b from pneumonia, 662 oxygen supplementation for, 596-603 I Ibuprofen, XIII:214-215 Ibuprofen toxicity, 162 Icterus. See Anemia, hemolytic; ­Hyperbilirubinemia Idiopathic feline hypercalcemia, 236-241, 238f, 239f, 240f Idoxuridine, for feline herpesvirus, 1188 Ifosfamide (IFEX) as chemotherapy, 311-312, 312t, XIII:474 for hemangiosarcoma, 330 for soft-tissue sarcomas, 326-327 IgA Deficiency, XIII:517 IgE, atopic disease and, 406, XIII:560 IgGd, atopic disease and, XIII:560 Imidacloprid, toxicity of, 123-124, XIII:235 Imidapril (Prilium), for dilated cardiomyopathy, in dogs, 794-795, 794t Imidazoline, toxicity of, XIII:153-157, XIII:156 Imidocarb dipropionate, for babesiosis, 1289t, 1290 Imipenem-cilastatin for bacterial pneumonia, 661t for Pseudomonas spp. ear infection, 435t for sepsis, XIII:273t minimum inhibitory concentrations (MIC) of, XIII:35t Imipramine for lower urinary tract disease, XIII:900t, XIII:901 for urinary incontinence, 957t, 958-959 Imiquimod, 424 for canine papillomaviruses, 445 for feline herpesvirus, 441 for feline papillomavirus, 442 Immiticide. See Melarsomine Immune system. See also Immunomodulary therapy glomerulonephritis and, in dogs, XIII:851-852 Immune-mediated dermatopathies nonsteroidal immunosuppressive therapy for, XIII:536 topical immune modulators for, 422 Immune-mediated disease. See also Anemia, hemolytic; Thrombocytopenia; specific disease

  Index Immune-mediated disease (Continued ) causing azotemia, 856b causing blepharitis, 1181-1182 causing retinal detachment, 1216 glomerulonephritis, 865-867 ocular, 1149 role of, in infective endocarditis, 787 Immune-mediated hemolytic anemia. See Anemia, hemolytic Immune-mediated thrombocytopenia. See under Thrombocytopenia Immunology, immunophenotyping and, in the dog, XIII:505-509 Immunization. See Vaccination Immunoassays. See Enzyme-linked ­immunosorbent assay (ELISA) Immunocytochemical staining for myasthenia gravis, 488, 490 for pericardial diagnosis, 829 Immunodeficiency causes of, XIII:254t hereditary and acquired causes of, XIII:516-520 (See also EVOLVE) infectious disease and, XIII:244-245 (See also EVOLVE) management of diseases of, XIII:520 of shar-pei dogs, XIII:517 severe combined, genetic test for, 1057t vaccination and, XIII:253-256 X-linked severe combined, XIII:516-517 Immunodiagnostics CDs and related molecules in, XIII:507t immunophenotyping and, in the dog, XIII:505-509 (See also EVOLVE) Immunofluorescence, for herpesvirus-1, in cats, XIII:1058 Immunofluorescent antibody (IFA) test for feline immunodeficiency virus, XIII:285 for feline leukemia virus, XIII:280-281 Immunohistochemistry for diagnosis of neoplasia, XIII:453-454 for feline gastrointestinal lymphoma, 340-341 for feline leukemia virus (FeLV), 340-341 for pythiosis, 1269 tissue processing for, XIII:453-454, XIII:454t Immunology hematopoietic cytokines and, XIII:408-414 infectious disease emergence and, XIII:244 Immunomodulary therapy effects of ursodeoxycholic acid as, 564 for feline immunodeficiency virus, XIII:287 for feline leukemia virus, XIII:283 for feline retrovirus, 1280-1282, 1281t for malignant melanoma, 381 for mammary cancer, 365 topical, 420-425 Immunophenotyping for canine lymphoma, 337-338, 338t for feline gastrointestinal lymphoma, 343 in the dog, XIII:505-509 (See also EVOLVE) Immunoprecipitation radioimmunoassay, for myasthenia gravis, 490 Immunoregulin. See Propionibacterium acnes (Immunoregulin) Immunosuppression, associated with ­hypothyroidism, XIII:328 Immunosuppressive drugs, 254-259, XIII:509-513 as potential nephrotoxins, 856b for autoimmune myasthenia gravis, 1109 for babesiosis, 1290 for chronic colitis, 518-519, 519t for immune-mediated hemolytic anemia, 269-270 for inflammatory bowel disease, 505 for masticatory muscle myositis, 1112-1113 for thrombocytopenia, 285-286, 286t glucocorticoids as, 400-405 link to infective endocarditis, 786 post organ transplantation, 904-905 Immunotherapy allergen-specific, 406, 415-420, 416b, 417b, 418b

1365

Immunotherapy (Continued ) for acral lick dermatitis, 471 for atopic disease, XIII:563-564 in cats, XIII:566-569 for feline pruritus, XIII:544-545 for Malassezia hypersensitivity, 456 for papillomaviruses, 445, XIII:571 ocular, 1149-1153 Impedance instruments, XIII:394-395 Imprints, for cytology, 301 Incontinence, urinary. See Urinary ­ incontinence Indirect immunofluorescence assay (IFA) for Bartonella spp, XIII:305 for ehrlichiosis, XIII:299 for feline coronavirus, XIII:292 Indolent ulcers, 1197-1200, XIII:1074 Indomethacin, toxicity of, 162, XIII:214-215, XIII:227 Industrial product poisoning, incidence of, XIII:206t Infection(s). See also Infectious disease(s) causing azotemia, 856b causing bacterial pneumonia, 658-660, 659b causing canine influenza, 1291-1294 causing endocarditis, 786-791 causing myocarditis, 804-808 causing pancreatitis, in cats, 539 causing pregnancy loss, 986-988 control of viral, in catteries, 1299-1305, 1300t, 1302t, 1303b empiric antimicrobial therapy for, 1225-1229, 1226t from Bordetella bronchiseptica, 646-649 Helicobacter-associated gastric disease, 492-497, 494f, 495f, 495t hospital-acquired bacterial, 1222-1225 in diabetics mellitus patients, 215 rational use of glucocorticoids with, 1230-1233, 1232t, 1233t urinary tract, 918-925 Infectious canine hepatitis ocular signs of, XIII:277 thrombocytopenia from, 282t, XIII:440, XIII:441t Infectious disease(s). See also under Bacteria; Fungal infection(s); Specific disorder antimicrobial therapy for, XIII:33-40 bacterial, cutaneous, differential diagnosis for, in cats, XIII:565t causing immunodeficiency, XIII:519 causing nonregenerative anemias, 272-273 causing thrombocytopenias, 282-284, 282-286, 282t-283t disinfectants and antiseptics for, XIII:258-262 emergence of, XIII:244-245 (See also EVOLVE) internet resources for, XIII:1114t molecular biology and, XIII:246-249 neutropenia from, XIII:267-272 ocular manifestations of, XIII:276-279, XIII:277t (See also EVOLVE) of the cornea, XIII:1073-1074 recurrent, of weimaraners, XIII:449t resistant, XIII:262-267 tick-borne, XIII:296-297 (See also EVOLVE) Infectious tracheobronchitis (ITB). See Tracheobronchitis Infertility effect of hypothyroidism on, in male dog, XIII:940-941 in cats, XIII:929-931 in dogs, XIII:925-929 Inflammation central nervous system causing vestibular signs, 1100 causing encephalitis and meningitis, 1070-1074 neutrophil function and, XIII:447-448 role of glucocorticoids on, 402 in valvular heart disease, 781

1366

  Index

Inflammatory bowel disease, XIII:644 causing chronic colitis, 515-520 causing protein-losing enteropathy, 512-513 diagnosis and treatment of, 501-506 effect of, on liver, XIII:668t, XIII:669 nutritional management of, XIII:654-655 ulcerative colitis, 521-523 with feline inflammatory liver disease, 577-578 Inflammatory diseases causing episcleritis, in dogs, 1191-1192, 1191t causing myopathies, 1112-1115 causing nonregenerative anemia, 274 role of, in disseminated intravascular coagulation, 287-289, 288f Inflammatory liver disease, in cats, 576-581, 577b Inflammatory mammary carcinoma, 366 Infliximab, for feline infectious peritonitis, 1297t Influenza, canine, 1291-1294 Infusion pumps, for fluid therapy, 52 Inhaled irritants with chronic bronchitis, 645 with tracheal collapse, 631f, 633 Inherited disorders. See also Congenital disease(s) DNA testing for, in dogs, XIII:909-913 of the reproductive tract, XIII:904-909 Injection site reactions, from drug(s), XIII:557t, XIII:559 Inotropic drugs See also specific drug e.g. Dopamine for dilated cardiomyopathy, in dogs, 795 for heart failure, 775-777, 779t for refractory heart failure, XIII:755 for shock, 6-7 Insect bite. See Bite(s) Insect growth regulator toxicity, 123-124, XIII:234-235 Insecticide poisoning, 93-99, 93t, 119-125, XIII:221-222, XIII:222t Insemination, for canine breeding, 983-985 Insulin. See also Diabetes mellitus; Insulinoma allergic reactions to, XIII:357 binding antibodies of, XIII:356 complications of, XIII:354-357 drugs that enhance secretion of, XIII:351-352 effectiveness of, XIII:349-350 for canine diabetes mellitus, 196-198 long-term monitoring of, 196-198 for diabetic ketoacidosis, 216-218, 217b for feline diabetes mellitus, 201-204 resistance of, 200 for hyperkalemia, 233, 952 inadequate absorption of, XIII:355-356 overdose of, XIII:355 poor response to, XIII:356t radioimmunoassay for, level of, XIII:358 reference values for, XIII:1221t resistance administration technique and, XIII:355 associated with hypothyroidism, XIII:329-330 concurrent disorders causing, XIII:356-357 Somogyi effect and, XIII:355 short duration of effect of, XIII:355 therapy, with oral hypoglycemics, XIII:353 Insulinoma, XIII:357-361 See also EVOLVE Intercerebral hemorrhage, causing stroke, 1075-1077 Interferon for canine papillomaviruses, 445-446 for dermatology, XIII:537-538 for feline herpesvirus, 441, XIII:1059 for feline immunodeficiency virus, XIII:287, XIII:290 for feline infectious peritonitis, 1296 for feline leukemia virus, 442, XIII:283, XIII:290 use of, 389-390 Interleukin 3 (IL-3), XIII:403, XIII:407 See also EVOLVE

Interleukin(s) cross-regulatory effects of, XIII:410f of clinical interest, XIII:411t sources and use of, XIII:408-409 (See also EVOLVE) Interluminal stenting for tracheal collapse, 635-641, 637f, 639f, 640f International normalization ratio (INR), 696 Intersex, 1034 Interstitial cell tumor, XIII:943, XIII:943f Interstitial cystitis. See Cystitis Interstitial lung diseases, 672-674, 673b Interventional radiology, in urinary diseases, 965-971 Intervertebral disc disease. See also Spinal cord disease cervical, XIII:992-1000 rehabilitation considerations for, 1134-1135, 1134b Intestinal gas, 523-527, 524t, 525b Intestinal lymphangiectasia, 512 protein-losing enteropathy from, XIII:641-642 Intestine bacterial overgrowth of, XIII:637-641 (See also EVOLVE) neoplasia of, XIII:623 permeability of, XIII:640 transit/motility of, XIII:611t, XIII:612t Intoxication. See Poisoning; Toxicity(ies) Intracavitary chemotherapy, 327 specimen collection for cytology, 302 Intracranial blindness, XIII:1040-1041 Intracranial pressure monitoring of, XIII:180-182 pathophysiology of, XIII:178 traumatic brain injury and, 33-35, 35t with strokes, 1076-1077 Intracranial tumors, treatment of, 1078-1083, 1079t, 1080t Intradermal testing (IDT) feline, 406 for Malassezia hypersensitivity, 455 Intralesional injection, for acral lick dermatitis lesions, 472 Intraocular neoplasia, 1156-1157, 1156f, 1157f Intraocular pressure (IOP) drugs that increase, 1211-1212 with feline glaucoma, 1207-1209, 1209f with uveitis, 1201 Intraosseous catheterization, 38 Intrapleural blockade, for pain management, 15 Intravenous fluids. See Fluid therapy Intravenous gamma-globulin (IVGG), for immune-mediated hemolytic anemia, 270 Intravenous techniques, for pain management, 88-89 Inulin clearance test, 869 Iodine adverse reactions to, in cats, XIII:241t as antiseptic, XIII:260 therapy, for hyperthyroidism, XIII:336 Iohexol clearance test, 870-871, 871b Iopanoic acid (Telepaque), for hyperthyroidism, 176t, 179 Ipodate (Orografin), for hyperthyroidism, 179 Ipomoea purga, 151t Iris atrophy, 1171 bombé, 1201, 1201f hypoplasia, 1171 Irish setter(s), canine granulocytopathy syndrome in, XIII:448-449 Iron deficiency anemia, erythrocyte morphologic characteristics of, XIII:383 Iron dextran, for iron deficiency anemia, 916 Iron toxicity, 114t, 115, XIII:209 Ischemia causing azotemia, 856b causing stroke, 1074-1076 from arterial thromboembolism with, 819, 822, 822t

Isoflurane adverse reactions of, in dogs, XIII:240t use of, in gastric dilatation-volvulus, 80 Isosorbide dinitrate, for refractory heart failure, XIII:754 Isosthenuria, 848 Isotretinoin (Accutane) as chemotherapy, XIII:476 for sebaceous adenitis, 452, XIII:573 ITP. See Thrombocytopenia Itraconazole (Sporanox) for central nervous system cryptococcosis, 1072-1073 for dermatophytosis, 460-461, 461t, XIII:579 for fungal rhinitis, 614, 625 for idiopathic rhinitis, 615 for Malassezia spp., 455t, 456, XIII:576 for Pseudomonas spp. ear infection, 435 for Pythium spp. infections, XIII:314 for respiratory tract fungal disease, XIII:817-819 toxicity, 625 Ivermectin. See also Heartworm disease for bronchopulmonary parasites, 667-671 for canine heartworm microfilaria, 841 for cheyletiellosis, 393 for Cuterebra spp., 667 for demodicosis, 394, 440 for ear mites, 393 for feline heartworm microfilaria, 835, 835t for Filaroides hirthi, 668 for fur mites, 394 for lice, 394 for nasal mites, 613, 624, 666-667 for Oslerus (Filaroides) osleri, 668 for sarcoptic mange, 393 for ticks, 394 genetic test for toxicity of, 1056t use of, in dermatology, 391 Ivermectin toxicity, 125-127, 391 Ixodids as vectors, XIII:296-297, XIII:297 diseases associated with, XIII:296t J Jackson Pratt drain, 75, 75f Jejunostomy feeding, after gastric dilatation-volvulus, 82 Jejunostomy tube(s), XIII:71t, XIII:72, XIII:72t Jimsonweed, 151t Joint disorders. See Osteoarthritis Joint injury, from degloving or shearing wounds, XIII:1034-1035 Jones test, 1144 Journal, in assessing information, XIII:2-8 Jugular catheter care, 43 Juvenile vulva, 1013-1014, 1014f K Kanamycin causing nephrotoxicity, 162 intravitreal, 1148t minimum inhibitory concentrations (MIC) of, XIII:35t nebulization of, 662 subconjunctival, 1147t toxicity of, XIII:214 Kava kava, associated liver disease, 568t Keeshond(s), growth-hormone responsive dermatosis in, XIII:376 Keflex. See Cephalexin Keflin. See Cephalothin Kefzol. See Cefazolin Kennel cough. See Tracheobronchitis Keratectomy, superficial, for nonhealing corneal ulcers, 1198-1199 Keratic precipitates, 1161-1162, 1162f, 1201f Keratinization disorder(s), essential fatty acids for, XIII:541 Keratitis. See also under Corneal; Eye associated with systemic infectious diseases, XIII:277t chronic superficial, XIII:1067 (See also EVOLVE)



  Index

Keratitis (Continued ) eosinophilic, XIII:1070 from feline herpesvirus, XIII:1060, XIII:1074 pigmentary, XIII:1067-1068 ulcerative, XIII:1071-1075 (See also EVOLVE) Keratoconjunctivitis sicca (KCS) associated with hypothyroidism, XIII:328 associated with sulfasalazine, 518-519 causing conjunctivitis, 1176, 1176f diagnosis and treatment of, XIII:1061-1066 (See also EVOLVE) keratitis from, XIII:1072-1073 Schirmer tear test for, 1143-1144 tear substitutes for, XIII:1064t vs. tear film disturbances, 1196 Keratopathy, bullous, XIII:1092 Keratotomy for nonhealing corneal ulcers, 1198-1199 superficial, XIII:1074 Kerosene toxicity, 134 Ketamine adverse reactions of, XIII:240t, XIII:241t and cardiac disease, in cats, XIII:101 cocktail with opioids, 11 for pain management, 11, 12f-13f, 16, 88-89 use of, XIII:123, XIII:125t Ketamine morphine lidocaine (MLK) CRI, 88-89 Ketoacidosis acid-base disorders in, 60 diabetic, 216-218 Ketoconazole (Nizoral) associated liver disease, 568t for central nervous system cryptococcosis, 1072-1073 for dermatophytosis, 460, 460t, XIII:579 for hyperadrenocorticism, 226, XIII:365 for Malassezia spp., 455t, 456, XIII:576 for perianal fistulas, 468, 529 for Pseudomonas spp. ear infection, 435 otic, 431t, 456 post organ transplantation, 905 shampoo, 414-415, 414t, 459t with cyclosporine, 387 Ketoprofen for anterior uveitis, 1206t for ocular diseases, 1151t for pain management, 14, 14t, 1128t toxicity of, XIII:227-229 Ketorolac (Toradol) for anterior uveitis, 1205, 1206t for ocular diseases, 1151t, 1152 for pain management, XIII:61 Kidney cancer of, 925-930 enlargement of, 926, 926b hyperthyroidism and the, XIII:337-339 (See also EVOLVE) indications for nephrectomy of, XIII:866-868 (See also EVOLVE) interventional radiology of, 965-967 normal size of, 925-926 transplant, 901-906 Kidney disease. See Renal disease; specific ­disease e.g. Pyelonephritis Kidney failure. See Renal failure Kidney stone(s). See Urolithiasis Kit mutations, 373, 377 Kitten. See under Neonatal medicine; Orphan(s) Klebsiella spp. causing urinary tract infections, 919, 920t, 1226 minimum inhibitory concentrations (MIC) for, XIII:35t, XIII:42t Kramer algorithm, 101b Krazy glue ingestion, 140 L l-Arginine.

See Arginine

l-Asparaginase

administration protocol for, XIII:464 as chemotherapy, 310, XIII:470 for feline gastrointestinal lymphoma, 342, 342t

l-Carnitine. l-Deprenyl

See Carnitine

drug interactions with, XIII:365 for canine cognitive dysfunction, XIII:53-57 for hyperadrenocorticism, XIII:364-366 uses of, XIII:364-365 l-MTP-PE, as chemotherapy, XIII:476 Labor and delivery, 992-998, 996f, 997f Laboratory diagnostics. See Laboratory test(s) Laboratory test(s). See also Diagnostic test(s) accuracy of, bedside vs. traditional, XIII:111 assays, for atopic disease, XIII:560-564 bedside, XIII:110-112 (See also EVOLVE) biochemistries, abnormalities in, differential diagnosis of, XIII:108t-109t blood-typing and crossmatching, 260-265 cardiac troponin, 805, 806f differential diagnosis for abnormalities in, XIII:105-109 effect of nonadrenal disease on adrenal function as, XIII:362-363 (See also EVOLVE) evaluation of elevated alkaline phosphatase, in dogs, 549-553, 551f flow cytometry, 338t for adrenal disease, interpretation of, XIII:321-324 for assessment of hydration, 49 for bacterial urinary tract infection, in cats, XIII:881-882 for brucellosis, 1235 for canine hereditary disorders, 1054-1059 for dermatologic diseases, XIII:526-530 for determination of surgery risk/benefit ratio, XIII:19t for diagnosis of acute abdomen, 69-71 for differentiation of acute and chronic renal failure, XIII:856-858 (See also EVOLVE) for disseminated intravascular coagulation, XIII:191-193 for drug monitoring See (Drug monitoring) for feline immunodeficiency virus, XIII:285 for feline leukemia virus, XIII:280-284 for heartworm disease in cats, 831-832, 832f in dogs, 838, 841-842 for immune-mediated hemolytic anemia, 266-269, 267t for liver disease, comparison of, in cats, XIII:673t-674t for monitoring craniocerebral trauma, XIII:181t for polyuria and polydipsia, XIII:833-834 for therapeutic drug monitoring, XIII:26-32 for thyroid disease, interpretation of, XIII:321-324 handling of tissues for, XIII:453f immunophenotyping as, XIII:505-509 (See also EVOLVE) interpretation of cytograms and histograms, XIII:381-390 (See also EVOLVE) molecular, XIII:455-456 of hereditary erythrocyte disorders, XIII:418 of lactate, XIII:112-116 (See also EVOLVE) techniques for cytology collection, 301-304 Laboratory(ies) for in-vitro allergy testing, XIII:561t hematology instrumentation for, XIII:391-396 Labrador retriever(s) dysautonomia in, XIII:957t inherited copper hepatitis, 561 Lacrimation, excessive, XIII:1055-1057. See also EVOLVE Lactate blood levels during shock, 3 requiring oxygen therapy, 597b with GDV, 77 fluid therapy and, 50-51 implications of, XIII:112-116. (See also EVOLVE) in sepsis, XIII:274

1367

Lactation agalactia, 1001 nutrition recommendations during, 1003-1007 suppression of, 1002 Lactic acidosis acid-base disorders in, 60 in ethylene glycol toxicosis, 161 shock and, 3 Lactoferrin, for feline retrovirus, 1281t, 1283 Lactose, dietary, XIII:654 Lactulose (Cephulac) for anal sac tumors, 384 for constipation, in cats, XIII:650, XIII:651t for hepatic encephalopathy, 571, 579 from portosystemic shunt, 584, 586 Lagenidiosis, 1268-1271 Lagophthalmos, XIII:1072 Lameness, from gracilis-semitendinosus myopathy, XIII:989-992 Lamina propria lymphocyte P-glycoprotein testing, 503 Lamivudine, for feline retrovirus, 1281t Langerhans cell histiocytosis, pathogenesis of, XIII:588 Lansoprazole (Prevacid) for acute renal failure, 881 for esophageal disease, 484, XIII:609 Lanyana essential oil, 152t Laparotomy in gastric dilatation-volvulus, 80 with septic abdomen, 73-74, 73f Large intestinal transit, assessment of, XIII:612t, XIII:613 Laryngeal collapse diagnosis and treatment of, 628-629 from brachycephalic upper airway ­ syndrome, 621 Laryngeal disease(s), 627-630 Laryngeal masses, 629 Laryngeal paralysis diagnosis and treatment of, 627-628 relationship to hypothyroidism, XIII:327 relationship to megaesophagus, 489 Laryngectomy, 628 Laryngitis, granulomatous, 629 Laryngoscopy, 627-628 Larynx, tumors of, XIII:502-503, XIII:503t Laser lithotripsy, 939, 940-943, 970 resection of soft palate, 620 resection of stenotic nares, 620 therapy, for papillomaviruses, XIII:571 Lavage, pleural space, 677 Lawn and garden product toxicity, XIII:206t, XIII:221-222 Laxative therapy, for constipation, in cats, XIII:650-651, XIII:651t Lead lines, 128 Lead toxicity, 114t, 115 causing kidney failure, 160b diagnosis and treatment of, 127-130 neutrophil dysfunction in, XIII:449t treatment of, XIII:209 Leflunomide, as immunosuppressive agent, 258, XIII:513 Legal, considerations in toxicity(ies), 105-108 Leiomyoma gastric, XIII:623 of the larynx and trachea, XIII:503t Leiomyosarcoma nasal and paranasal, XIII:501t polyuria and polydipsia from, 847t Leishmaniasis diagnosis and treatment of, 1252-1254 interleukin(s) and, XIII:411 ocular signs of, XIII:279 thrombocytopenia from, 283t, XIII:441t Lens. See also Cataract drug therapy for, 1148 induced uveitis, 1204 opacification, causing blindness, 1165, XIII:1039 Lens luxation corneal edema from, 1160f feline glaucoma from, 1213

1368

  Index

Lenticular sclerosis, 1165 Leptospirosis azotemia from, 856b, 857-859 diagnosis and treatment of, 1237-1240, XIII:308-310 polyuria and polydipsia from, 847t thrombocytopenia from, 283t, XIII:440, XIII:441t vaccine recommendations for, 1273, 1273t Leucine crystalluria, 851t Leukemia. See also Feline leukemia virus causing nonregenerative anemia, 275 cytograms and histograms of leukocytes demonstrating, XIII:386f immunophenotyping for, XIII:508-509 on scattergrams and histograms, XIII:384 Leukocyte adherence deficiency, XIII:518 Leukocyte(s), cytograms abnormal, XIII:385f-386f and histograms of, XIII:383-384 interpretation of, XIII:381-390 (See also EVOLVE) normal, XIII:384f Leukocytosis, from hepatozoonosis, XIII:311 Leukopenia, parvovirus and, XIII:629 Leukotrienes, causing airway inflammation, 656 Levamisole for feline retrovirus, 1281t for systemic lupus erythematosus, XIII:515 Levetiracetam for seizures, 1067-1068 for status epilepticus, 1064 Levothyroxine for hypothyroidism, 189 for myxedema coma, XIII:329 monitoring replacement of, XIII:331-332 pharmacology of, XIII:331 therapeutic trial for hypothyroidism, 188 Liability, of vaccination, XIII:252 Lice, treatments for, 394 Lich-Gregior technique, 934 Lick granuloma. See Acral lick dermatitis Lidocaine for arterial cutdown procedure, 41 for epidural analgesia/anesthesia, XIII:126-127, XIII:127t for pain management, 12f-13f, 14-16 for supraventricular tachyarrhythmias, 726 for ventricular arrhythmias, 729, 738, XIII:734-735 in cats, 818 with gastric dilatation-volvulus, 79-80, XIII:166 with heart failure, 775, 777 in cats, XIII:101 local for pain management, XIII:60 in critical care, XIII:124 patches, 16 topical in nasopharynx, 623 toxicity of, 729, 738 use during CPR, 31 Lidocaine morphine ketamine (MLK) CRI, 16t, 88-89 Life support, and CPR, 28-32 Lily toxicity, 143, 160b, 163, 856b Limb salvage surgery, for osteosarcoma, 360 Lime sulfur dip for dermatophytosis, 459t for feline demodicosis, 440 Limonene, 120b, 122 Linalool, 120b, 122 Lincomycin, for pyoderma, 1226t, 1227 Linear accelerators, XIII:483 Linoleic acid, sources of, XIII:538-539 Linoleum, 127 Lipemia. See also Hypercholesterolemia; Hyperlipidemia; Hypertriglyceridemia hyponatremia and, XIII:375 Lipid emulsion(s), in nutritional support, 19 Lipid(s) dietary, and renal failure, XIII:862 for sepsis, XIII:275 metabolism in diabetes mellitus, 206

Lipoprotein skin lesions, 462-463 Liposomal muramyl tripeptide phosphatidylethanolamine (L-MTP-PE), for hemangiosarcoma, 331 Liposome-encapsulated clodronate, for immune-mediated hemolytic anemia, 270 Liposome-encapsulated drug delivery, with chemotherapy, XIII:478 Lipotoxicity, 200 Lipoxygenase (LOX) pathways, 1129f Lipstick ingestion, 111 Lisinopril adverse effects of, 794-795 effect of, on proteinuria, XIII:852 for dilated cardiomyopathy, in dogs, 794-795, 794t for heart failure, 772-774 Lithium, toxicity of, 160b Lithotripsy, laser, 940-943 Liver biopsy of, 548-549, 571, 577, XIII:662-663, XIII:671 effect of, extrahepatic disease on, XIII:668-671, XIII:668t enzyme elevation, 544-547 differential diagnosis of, XIII:670f from drug-associated disease, 567, 568t of alkaline phosphatase, in dogs, 549-553, 551f, 552b, 553b with biliary mucocele, 587-588 with hepatic lipidosis, 570-571 with portosystemic shunt, 582 reactive changes of, XIII:668-669 ultrasound of, XIII:661 Liver alkaline phosphatase (L-ALP), 545, 549-550 Liver disease. See also under Hepatic; Hepatic encephalopathy; Hepatic lipidosis associated ascites, 556-557 associated coagulopathy, 556 associated with tracheal collapse, 633 biliary clinical findings in, XIII:659t diagnostic approach to, XIII:659-664 carbohydrate metabolism and, XIII:695 cholangiohepatitis. See (Cholangiohepatitis) diagnostic approach to, 543-549 dietary implications of, XIII:694t drug-associated, 566-569, 567b, 568t fat metabolism and, XIII:695 fibrosis, XIII:677-681 from canine biliary mucocele, 587-589 from copper, 557-562, 559b from flukes, 580 from portosystemic shunts, 581-586 hepatic lipidosis, 570-575 hepatitis See (Hepatitis) hepatotoxins causing, XIII:217-219 inflammatory, in cats, 576-581 lawn care products causing, XIII:222 lipidosis See (Hepatic lipidosis) microvascular dysplasia (See Hepatoportal microvascular dysplasia) nodular hyperplasia of, XIII:670-671, XIII:675-676 protein metabolism and, XIII:694-695 therapy of homemade diets for, XIII:696t nutritional management of, XIII:693-697 supportive, 554-557 ursodeoxycholic acid, 563-565 vitamin K deficiency and, XIII:695 Liver enzymes, abnormalities of, 670f, XIII:660 Liver failure, polyuria from, 846t, XIII:832-833 Liver flukes, 580 Lobaplatin, as chemotherapy, XIII:475 Lomustine as chemotherapy, 309-310, XIII:474 associated liver disease, 568t effect on kidney, 930 for histiocytic diseases, 349-351 for intracranial tumors, 1079t, 1081 for mast cell tumors, 376-377, 377b

Low-dose dexamethasone suppression testing effects of nonadrenal disease on, XIII:362-363 for hyperadrenocorticism, 220 Low-molecular weight heparin, 26-27, 27f. See also Heparin Lufenuron adverse reactions of, XIII:240t, XIII:241t for dermatophytosis, 461 toxicity of, 123-124, XIII:234-235 Lung computed tomography for disease of, XIII:710 disease causing pulmonary hypertension, 698, 698b, 702 injury from ventilator therapy, 605-607 interstitial diseases of the, 672-674 Lung lobe torsion, 683-684 Lung resistance-associated protein, XIII:481 Lung tumors. See Neoplasia, lung Lungworms, 667-671. See also specific parasites Lupus erythematosus. See Systemic lupus erythematosus Luteinizing hormone during normal gestation, 992 measurement of, XIII:914-915 relation to ovulation, 975-979, 975f, 975t, 976f surge of, XIII:924t Lyme disease azotemia from, 859 diagnosis of, polymerase chain reaction for, XIII:248 infectious disease emergency and, XIII:244 myocarditis from, 808 serology of, with vaccination, XIII:257 thrombocytopenia from, XIII:440, XIII:441t vaccination for, XIII:256-258 vector associated with, XIII:296t Lymph nodes role of, in cancer removal, 322 with mammary cancer, 364 with mast cell tumors, 374 Lymphangiectasia, intestinal, 512 Lymphocyte(s) immunophenotyping and, in the dog, XIII:505-509 interleukins from, XIII:408-414 Lymphocytic cholangitis, 579-580 Lymphocytic portal hepatitis, 580-581 Lymphocytic thyroiditis, 185-191 Lymphocytic-plasmacytic colitis, 516 Lymphocytic-plasmacytic enteritis, 501-506, 512 effect of, on liver, XIII:669 Lymphoma canine cancer cachexia in, XIII:459 chemotherapy drugs for, 309-314 CHOP protocol for, 336-337, 337t diagnosis and treatment of, 336-339 nasopharyngeal, 626 protocols for, 306t, XIII:471-473 VELCAP protocol for, 306t causing anterior uveitis, 1203b, 1204 causing neuropathies, 1115 causing nonregenerative anemia, 275 chronic colitis and, XIII:646 feline cardiac, 356 chemotherapy drugs for, 309-314 gastrointestinal, 340-343, 342t mediastinal, 682 nasal, 353, 626 ocular, 1157, 1157f, 1183 gastrointestinal, XIII:623-624 hypercalcemia and, 247-248 immunophenotyping for, XIII:506-508 intestinal, XIII:623-624 intracranial, 1081-1082 mediastinal, 355-356, 355f nasal and paranasal, XIII:501t of larynx and trachea, XIII:503t of nasal plane, XIII:500t optic, XIII:1097

Lymphoma (Continued ) renal, 928-929 retrovirus and, neurologic disease with, XIII:290 therapy of, multidrug resistance to, XIII:479 Lymphomatoid granulomatosis lung, XIII:504t of the nasal plane, XIII:500t Lymphopenia, role of glucocorticoids on, 402 Lymphoplasmacytic enteritis, protein-losing enteropathy from, XIII:642 Lymphoplasmacytic rhinitis, 611f, 614-615 Lymphosarcoma. See Lymphoma Lymphosacral stenosis, degenerative, 1094-1096 Lysine for feline herpesvirus, 1301, XIII:1059 for feline rhinitis, 618 Lysodren. See Hyperadrenocorticism; Mitotane M Ma Huang toxicity, 151 Macadamia nut toxicity, 109 Maculopapular eruptions, from drug hypersensitivity, XIII:557t Macrolides for canine heartworm prevention, XIII:780 for feline heartworm prevention, 835, 835t switching products in canine heartworm prevention, 842 Macrophage colony-stimulating factor (M-CSF), XIII:403 Macular papular lesions, from drug therapy, XIII:557 Magnesium. See also Hypomagnesemia antiarrhythmic use of, 32 in gastric dilatation-volvulus, 79, 81 concentration of, in colloid fluids, 63t dietary, recommendations in heart disease, 706-707, XIII:714 role of, in hyperparathyroidism, 242-243 supplementation of, in fluid therapy with diabetic ketoacidosis, 218b with hepatic lipidosis, 573-574 Magnesium ammonium phosphate, compound uroliths with, XIII:875-876 Magnetic resonance imaging (MRI) for atlantoaxial subluxation, 1085 for degenerative lymphosacral stenosis, 1095 for encephalitis and meningitis, 1071-1072 for feline right ventricular cardiomyopathy, 816-817 for strokes, 1075 for supraspinatus tendon disorders, 1118-1119 for syringomyelia and Chiari-like malformation, 1103f, 1104, 1106f for vestibular disease, 1099f, 1100f, 1101 of adrenal masses, XIII:370 of pituitary gland, XIII:367 to evaluate pericardial effusion, 829, 829f Maine coon cats, with feline cardiomyopathy, 811 Maintenance energy requirement (MER), 207, 207t MalAcetic Otic, 430t Malassezia infection(s) causing blepharitis, 1179 dermatitis diagnosis and treatment of, 453-457, 455t feline, 406 hypersensitivity to, 453-457 shampoo therapy for, 414, 414t skin scraping for, XIII:527 differential diagnosis for, in cats, XIII:565t otitis, 453-457 topical treatment of, 428-433 Malignancy, hypercalcemia associated with, 343-347 Malignant histiocytosis, XIII:591 causing nonregenerative anemia, 276 lung, XIII:504t ocular, 1156 Malignant lymphoma. See Lymphoma

  Index Malignant melanoma. See Melanoma, malignant Malnutrition, causing diarrhea in neonates, XIII:625-626 Mammary neoplasia canine, 363-366, 364t comparison between canine and feline, 366t feline, 366-368, 367t prognosis for, 366t staging systems for, 365t Mammomonogamus ierei, 666 Mandragora officinarum, 151t Mannitol for acute renal failure, XIII:176 for cerebrovascular disease, 1077 for glaucoma, XIII:1093 for oliguric renal failure, 880, 880t, XIII:849 for traumatic brain injury, 35, 35t, XIII:183 with intracranial tumors, 1079t Manometry, for esophageal evaluation, 489 Marbofloxacin for mycoplasmosis, 1247 for Pseudomonas spp. ear infection, 435t otic, 431t Marijuana toxicity, 145 Marin. See Silybin-phosphatidylcholine (Marin) Maropitant citrate (Cerenia) for acute renal failure, 881 for pancreatitis, 536 use of, with chemotherapy, 308 Mast cell tumor(s) breeds at risk, 374 chemotherapy protocol for, 377b diagnosis and treatment of, 373-378 eyelid, 1183 immunophenotyping for, XIII:506 of the larynx and trachea, XIII:503t of the nasal plane, XIII:500t postsurgical recommendations, 376b prognosis for, 375-376 radiotherapy for, 318, XIII:482-485 Masticatory muscle myositis, 1112-1113, XIII:1087-1088 Mastitis, septic, 1001, 1001f Maternal antibody, vaccination and, XIII:252 MDR1 genotype test, 668 Mebendazole adverse reactions of, in dogs, XIII:240t associated liver disease, 568t Mechlorethamine administration protocol for, XIII:464-465 as chemotherapy, 309 Meclofenamic acid, adverse reactions of, in dogs, XIII:240t Medetomidine, XIII:122 for epidural analgesia/anesthesia, dosage of, XIII:127t for pain management, 12f, 13, 13t, 1128t Mediastinal lymphoma. See Lymphoma Mediastinal mass, causing chylothorax, 678 Medical records, legal considerations for, 106-107 Medication(s) approximate dosages of, 1306-1334 tips for administration of, 705b Medium-chain triglyceride (MCT) oil for chylothorax, 679 for protein-losing enteropathy, 514, XIII:643 Medroxyprogesterone acetate adverse effects of, 1027, 1047 for benign prostatic hypertrophy, 1047 for estrus suppression, 1024-1025, 1027 for intermittent erection in male castrated dogs, 1053 ingestion, 148 Medulloepithelioma, in dogs, XIII:1095 Megacolon, feline, XIII:648-652, XIII:651t, XIII:652 See also EVOLVE Megaesophagus. See also Esophagus associated with hypothyroidism, XIII:327 canine, 486-492, 487b, XIII:602-607 from myasthenia gravis, XIII:605 Megakaryocyte(s), on scattergrams and histograms, XIII:384

1369

Megestrol acetate (Ovaban) adverse effects of, 1027 associated liver disease, 568t during estrus suppression, 1026-1027 for benign prostatic hypertrophy, 1047 for false pregnancy, 991 for feline pruritus, XIII:544 for intermittent erection in male castrated dogs, 1053 ingestion of, 148, 148t Meglumine antimonite, for leishmaniasis, 1253 Meibomian gland adenoma, 1154, 1183 Melaleuca oil toxicity, 120b, 123, 153 Melamine, causing nephrotoxicity, 164-165 Melanoma adnexal, 1154 intraocular, 1156, 1156f, 1157f malignant diagnosis and treatment of, 378-382 vaccination, 381 of the larynx, XIII:503t of the nasal plane, XIII:500t optic in cats, XIII:1095-1096 in dogs, XIII:1094-1095 Melarsomine dihydrochloride (Immiticide). See also Heartworm disease administration of, XIII:788-789 adverse reactions to, 839-841 current uses and hazards of, XIII:787-790 for canine heartworm disease, 839-841, 840f for feline heartworm disease, 835 Melatonin clinical use of, XIII:548-549 for hyperadrenocorticism, 223 therapy, for canine alopecia, XIII:546-549 Meloxicam for anterior uveitis, 1206t for neurologic and musculoskeletal pain, 1128t for ocular diseases, 1151t, 1152 for pain management, 12f-13f, 14, 14t Melphalan (Alkeran) as chemotherapy, 309, XIII:467 for anal sac tumors, 384 Meningioma causing vestibular signs, 1100 treatment of, 1079-1080 vestibular signs from, XIII:969 Meningitis causing vestibular signs, 1100 diagnosis and treatment of, 1070-1074 use of glucocorticoids with, 1231 Meningitis-arteritis, steroid responsive, in dogs, XIII:978-981 Meningoencephalomyelitis, 1070-1074 Meperidine, 11, 11t Mercury, causing nephrotoxicity, 160b Meropenem, for Pseudomonas spp. ear infection, 435t Mesalamine, for chronic colitis, 518-519, 519t Mesenteric lymphangiography, with thoracic duct ligation, 681 Mesna, XIII:474, XIII:476-477 Meso-2,3 dimercaptosuccinic acid (DMSA, succimer), 114t, 115 Mesothelioma, 354-355 pleural, 682 Metabolic acid-base disorders, 58-61 Metabolic acidosis. See under Acidosis causing azotemia, 856b in chronic kidney disease, 873t, 876, 889t in feline urethral obstruction, 951-952 in hypoadrenocorticism, 234 Metabolic alkalosis. See under Alkalosis Metabolic complications, of parenteral nutrition, 23 Metabolic disorder(s) associated with obesity, 192b causing azotemia, 856b causing immunodeficiency, XIII:519-520 effect of, on liver, XIII:670

1370

  Index

Metaldehyde toxicity, 97t Metals and pet food safety, XIII:237 Metals toxicity, 114t, 115 causing nephrotoxicity, 160b, 856b Metaproterenol toxicity, XIII:154, XIII:154t Metastasis. See Neoplasia Metatarsal fistulation, of German shepherds, 423 Metered-dose inhaler(s) Aerokat, 656-657, 657f of albuterol, 655, 656-657 of fluticasone propionate (Flovent), 643, 656-657 Metformin, XIII:351t, XIII:352 Methamphetamine toxicity. See Amphetamine toxicity Methanol toxicosis, 134-135 Methazolamide, for feline glaucoma, 1210-1211, 1210t Methemoglobinemia, Heinz body anemia and, XIII:421 Methenamine, as urinary tract antiseptic, XIII:889-890 Methicillin-resistant canine pyoderma, 449-450 Methimazole (Tapazole), XIII:334t adverse effects of, XIII:335-336, XIII:335t associated liver disease, 568t before radioiodine therapy, 178, 180 dosage of, XIII:334t for hyperthyroidism, 175-179, 176t, 180, XIII:334-336 with kidney failure, XIII:339 Methionine-dl, for feline lower urinary tract disease, XIII:889t Methocarbamol, for strychnine toxicosis, 118 Methoprene toxicity, 123-124, 124 Methotrexate, XIII:510 administration protocol for, XIII:464 as immunosuppressive agent, 254 causing nephrotoxicity, 160b, 930 for chemotherapy, XIII:467-468 for feline gastrointestinal lymphoma, 342t Methoxyflurane, causing nephrotoxicity, 160b Methoxymorpholino-doxorubicin, as chemotherapy, XIII:475 Methylene blue as urinary tract antiseptic, XIII:891 Heinz body anemia from, XIII:421 Methylprazole (4-Methylprazole, 4-MP), for ethylene glycol toxicity, XIII:207t, XIII:209, XIII:214 Methylprednisolone adverse effects of, 654, XIII:241t comparison of, to other glucocorticoids, 401t definition of, 401-402 for episcleritis, in dogs, 1191t, 1192 for feline chronic bronchitis or asthma, 654 for feline pruritus, 407-408 for intracranial tumors, 1079t for spinal cord disease, XIII:188-189 subconjunctival, 1147t, 1206t use of, with infectious diseases, 1232 Methylxanthine derivatives adverse effects of, 644 bronchodilators, 644, 655 for chronic bronchitis, XIII:803 pentoxifylline, 397-400 Methylmethacrylate bone cement, for cervical vertebral instability, XIII:998-999 Metoclopramide (Reglan) constant rate infusion of, 881 for esophagitis, 484 for gastric dilatation-volvulus, 81 for megaesophagus, 491 for pancreatitis, 536 for parvoviral enteritis, XIII:631, XIII:631t for renal failure, 881, XIII:865, XIII:865t for vomiting cats, 574 interactions with, XIII:614-615 use of, XIII:614-615, XIII:615t Metoprolol for beta-agonist toxicity, XIII:155 for dilated cardiomyopathy, in dogs, 796 for heart failure, 772-775 for hypertension, with renal disease, 912t

Metritis, 999-1000, 1000t Metronidazole (Flagyl) for chronic colitis, 519, 519t, XIII:648 for Helicobacter spp. infection, 495-496, 495f for hepatic encephalopathy, 571 for inflammatory bowel disease, 503, 505 for neutropenia, XIII:271 for sepsis, XIII:273t toxicity, 114t, 115, 519-520, 1099 vestibular signs from, XIII:968-970 Mexiletine for pain management, 16-17 for syncope, 712t for ventricular arrhythmias, 729, 796, XIII:735 in boxers, 799 in Doberman pinscher cardiomyopathy, 802 with heart failure, 775, 777 Mibolerone (Cheque drops) for estrus suppression, 1028 for false pregnancy, 991 Miconazole cream, toxicity of, XIII:230 otic therapy, 431t, 456 shampoo, 414-415, 414t Miconazole-chlorhexidine rinse, for dermatophytosis, 459, 459t Microalbuminuria, 861 Microchip(s), XIII:93-95, XIII:94t Microenteral nutrition, XIII:136-140, XIII:137t-138t. See also Enteral nutrition; EVOLVE Microfilaria testing, 833, 838 in cats, XIII:784 in dogs, XIII:779-780 Micronutrients, in diabetic diets, 206-207 Microorganisms, effectiveness of disinfectants and antiseptics against, XIII:259t Microscopic agglutination test (MAT), for leptospirosis, 859, 1238, XIII:308 Microsporum spp., 457-461, XIII:577-580 Micturition disorders, management of, 955-959, 956t Midazolam, XIII:122-123, XIII:125t in traumatic brain injuries, 35t Mifepristone (RU486), for canine pregnancy termination, 1032 Milbemycin oxime. See also Heartworm disease adverse reactions of, in dogs, XIII:240t for canine heartworm microfilaria, 841 for cheyletiellosis, 394 for demodicosis, 394 for feline heartworm disease prevention, 835, 835t, XIII:786 for nasal mites, 624, 667 for sarcoptic mange, 393 toxicity of, 125-127 use of, in dermatology, 392 Milk thistle. See Silymarin Mineral oil bath, for sebaceous adenitis, 452 Mineralocorticoid(s) See specific hormones and drugs Minimum inhibitory concentration (MIC), 920, 1225-1226 of antibiotics, XIII:35t of quinolones, XIII:42t Minoxidil toxicity, 138-139, XIII:230-231 Miosis, 1171-1172, 1200-1201 conditions that cause, XIII:1047 Miotic drug(s), for glaucoma, XIII:1079 Mismating. See under Pregnancy, termination of Misoprostol for canine pregnancy termination, 1032 for gastric ulceration, 500 for gastrointestinal disorders, due to shock, XIII:144 Mithramycin, for hypercalcemia of malignancy, 346f, 347 Mitotane (o,p’-DDD, Lysodren) causing iatrogenic hypoadrenocorticism, 231 for adrenal masses, XIII:371 for hyperadrenocorticism, 223, 225, 227, XIII:365 monitoring of, 171, XIII:321

Mitotic inhibitors, 311 Mitoxantrone administration protocol for, XIII:464 as chemotherapy, 310, XIII:469 for bladder cancer, 372 for soft-tissue sarcomas, 326-327 Mitral regurgitation asymptomatic, 776 causing syncope, 710, 710b from infective endocarditis, 786-791 in Doberman pinschers, 801 treatment of, 772-776 valvular heart disease causing, 780-786 work-up of dog with, 772 Mitral valve dysplasia canine, 765-768 feline, XIII:739t, XIII:740t Mitratapide (Yarvitan), 195 Moisturizing shampoos, 411, 411t Mold, causing aflatoxicosis, 156-159 Molecular biology, XIII:246-249, XIII:247t Molecular diagnostics, XIII:455-456 problems with, XIII:249 Mometasone, 429, 432t Monitoring. See Blood pressure Critical care; Laboratory drug therapy (See Drug monitoring) Monoclonal antibodies. See under Antibody(ies) Monocyte(s) effect of granulocyte-monocyte colonystimulating factor on, XIII:404 interleukins from, XIII:408-414 Montelukast, for feline airway inflammation, 656 MOPP (Mechlorethamine, Vincristine, Procarbazine, Prednisone), XIII:473 Mormon tea toxicity, 151 Morphine acute abdomen and, XIII:164 constant-rate infusion (CRI) of, 88-89 epidural, XIII:127-128 for acute abdomen, 71 for epidural analgesia/anesthesia, XIII:127t for neurologic and musculoskeletal pain, 1128t for pain management, 11, 11t, 12f-13f, 88-89, XIII:59t toxicity, 145-146 Morphine lidocaine ketamine (MLK) CRI, 16t, 88-89 Mosquito product toxicity, 111 Motor oil toxicity, 134 Moxidectin for demodicosis, 394 for ear mites, 393 for sarcoptic mange, 393 toxicity of, 125-127 use of, in dermatology, 392 MPG (2-MPG, Thiola), for feline lower urinary tract disease, XIII:889t Mucopolysaccharidosis autosomal recessive inheritance of, XIII:910t genetic tests for, 1056t Mucosal perinuclear antineutrophilic cytoplasmic antibody (pANCA) testing, 503 Müllerian duct derivatives, in disorders of sexual development, XIII:905t Müllerian duct syndrome, 1037-1038, XIII:906-907 Multidrug resistance, XIII:479-482, XIII:480t. See also EVOLVE (MDR-1) gene, 125-126, 391 with urinary tract infection, 921-925 Multiple myeloma. See Myeloma, multiple Mupirocin, for pyoderma, 1227 Muritan toxicity, XIII:215-216 Murmurs. See Heart murmur(s) Muscle biopsy(ies), for dysphagia, 481 Muscular dystrophy, X-linked inheritance of, XIII:910t Musculoskeletal infections, empiric ­antimicrobial therapy for, 1226-1227 Musculoskeletal pain management, 1126-1131, 1127t Mushrooms, causing nephrotoxicity, 160b, 856b

Mustard essential oil, 152t Myasthenia gravis acquired, from methimazole, 177 acute fulminating, 1110 and hypothyroidism, 186 autoimmune, diagnosis and treatment of, 1108-1111 diagnosis of, 488, 490 dysphagia from, 480-481 megaesophagus and, 487b, 488, XIII:603, XIII:605 treatment of, 490 Mycobacteriosis effectiveness of disinfectants and antiseptics against, XIII:259t resistance of, XIII:262 treatment of, in cats, XIII:103 Mycophenolate mofetil (MMF) as immunosuppressive agent, 257-258, XIII:513 for autoimmune myasthenia gravis, 1110 for immune-mediated hemolytic anemia, 270 for thrombocytopenia, 286t Mycoplasma spp causing conjunctivitis, 1177 causing pregnancy loss, 987 Mycoplasmosis diagnosis and treatment of, 1245-1248, 1248f feline bronchitis from, 653, 656 immune-mediated hemolytic anemia and, XIII:430 pneumonia from, 659 thrombocytopenia from, 282t, XIII:441t vector associated with, XIII:296t Mycoses. See Fungal infection Mycotoxins causing nephrotoxicity, 160b in pet foods, XIII:237 Mydriasis, 1171-1172 conditions that cause, XIII:1047 Mydriatic(s), subconjunctival, 1146, 1147t Myelodysplastic syndromes, 275 Myelofibrosis, 274 Myelography for cervical vertebral instabilitymalformation syndromes, XIII:994t with atlantoaxial subluxation, 1085 Myeloma, multiple, causing nonregenerative anemia, 276 Myelonecrosis, 274 Myelopoietic factors, XIII:403-408. See also EVOLVE Myelotoxic drugs, 254 Myocardial disease. See also under Cardiomyopathy diagnosis and treatment of, in cats, 809-815 feline, XIII:762-767 right ventricular in cats, 815-818 Myocardial infarction, feline, XIII:762-763 Myocarditis causing ventricular arrhythmias, 729 diagnosis and treatment of, 804-808, 805t, 806f feline, 807 traumatic, ventricular arrhythmias and, XIII:731 Myopathy(ies) congenital myotonia in cats as, XIII:987-989 dysphagia from, 480-482 gracilis-semitendinosus, XIII:989-992 hypokalemic, in cats, 1136-1138, 1136b, 1137f, 1137t, XIII:985-987 megaesophagus from, 486-488 treatment of, 1111-1114 Myositis, masticatory, XIII:1087-1088 Myotomy for dysphagia, 481 for megaesophagus, 491 Myotonia congenital, in cats, XIII:987-989 genetic test for, 1056t

  Index Myxedema coma, from hypothyroidism, 186, XIII:328-329 N N-acetylcysteine (Mucomyst), for ­acetaminophen toxicity, XIII:219 n-Butyl chloride, adverse reactions of, in cats, XIII:241t Nail bed papillomas, 444-445 Nalbuphine, for pain management, XIII:59t Naloxone, XIII:125t for opioid reversal, 11, 145-146 Naltrexone for opioid reversal, 11 for sensory mutilation, XIII:91, XIII:92t Naproxen causing nephrotoxicity, 162 toxicity of, XIII:214-215, XIII:227-228 Narcolepsy, genetic test for, 1056t Nasal aspergillosis. See Aspergillosis, nasal Nasal catheters, for oxygen delivery, 599 Nasal discharge in cats, 616-618 in dogs, 609-616, 610b, 611f Nasal mites, 613, 623, 624, 666-667 Nasal polyps. See under Polyps Nasal tumors diagnosis and treatment of, 352-353, 611f, 615-616 malignant, XIII:500t of cavity, XIII:501-502 of plane, XIII:500-504 radiotherapy for, 318, 352-353 Nasal, infusion of clotrimazole, technique for, XIII:315-317, XIII:316f Nasoesophageal tube(s), XIII:71t, XIII:72, XIII:72t Nasogastric tube(s), XIII:71t, XIII:72, XIII:72t Nasolacrimal drainage, 1146 obstruction, XIII:1056-1057 puncta cannulation, 1144 Nasopharyngeal disorders cryptococcosis, 624-625 cysts, 626 diagnosis and treatment of, 622-626 foreign body, 624 neoplasia, 626 parasites, 612, 623-624 polyps, 625, XIII:794-796 (See also EVOLVE) stenosis, 625-626 Nasopharyngoscopy, 623 Natriuretic peptides, 783 Nebulization effect of, on airway management, XIII:791 of gentamicin, 644, 662 of kanamycin, 644 of polymyxin B, 644 of saline, 662 Neomycin adverse reactions of, in cats, XIII:241t for hepatic encephalopathy, 571, 579 otic, 431t Neonatal encephalopathy, genetic test for, 1056t Neonatal medicine diarrhea in, XIII:625-628 feeding in, XIII:625-626 Neoplasia. See also Chemotherapy; Radiation therapy specific etiology (e.g. Lymphoma) or site (e.g. Mammary) anal sac, 382-384, 467, 528 associated with obesity, 192b bladder, 369-373 urinary tract infection and, XIII:886 canine lymphoma, 336-339 cardiac, 356, 826 pericardial effusion from, 825-831, XIII:773, XIII:776 cardiopulmonary, computed tomography for, XIII:709-710 (See also EVOLVE) causing arterial thromboembolism, 821f causing immunodeficiency, XIII:520 causing retinal detachment, 1216 chemotherapy for (See Chemotherapy)

1371

Neoplasia (Continued ) diagnosis of, strategies for, XIII:452-458 ear, 1099 eyelid, XIII:1052 and periocular skin, 1183 feline gastrointestinal lymphoma, 340-343 gastrointestinal, XIII:622-624 glaucoma from, 1212-1213 Heinz body formation in, XIII:422 hypercalcemia associated with, 343-347 intracranial, 1078-1083, 1079t, 1080t kidney, 925-930, 927f laryngeal, 629 lung, 354, XIII:503-504 malignant histiocytosis, 348-351 mammary, 363-368 mast cell tumors, 373-378 melanoma malignant, 378-382 nasal, 352-353, 615-616, XIII:500-502 nasopharyngeal, 626 ocular, 1153-1158, 1154f, 1155f, 1156f, 1157f, 1183, XIII:1094-1097, XIII:1094t, XIII:1097t of major vessels, 356-357 osteosarcoma, 358-362, 361t pancreatic, in cats, 541-542 pleural effusion from, 682-684 pulmonary, 354-357 rectal, 530 renal, nephrotomy and, XIII:867 respiratory tract, XIII:500-504 role of, in disseminated intravascular coagulation, 287-289, 288f soft-tissue, 324-328 splenic, XIII:521-522 surgical principles with, 320-324 testicular, XIII:943-944 therapy of chemotherapy guidelines, XIII:465-473 drug extravasation, XIII:465 drugs and protocols for, 305-314, XIII:465-473, XIII:474-478 gene therapy for, XIII:493-497 hyperthermia for, XIII:486-494 immunosuppressive agents as, XIII:509-513 interleukins for, XIII:410-414 multidrug resistance to, XIII:479-482 (See also EVOLVE) neutropenia with, XIII:271 practical mechanics of, XIII:462-465 radiotherapy for, 315-319, XIII:482-485 See also (Radiation therapy) urethra, 968-970 vaccine recommendations with, XIII:255 with diabetes mellitus, 215 Neoplastic effusion, medical and surgical management of, XIII:824 Neoral (Sandoz). See Cyclosporine Neosporosis, causing myositis, 1113-1115 Neostigmine, for myasthenia gravis, 490 Nephrectomy, 935 for renal tumors, 927-930 indications for, XIII:866-868 (See also EVOLVE) Nephritis, hereditary, 867, 1056t Nephroblastomas, 927-928 Nephrolithiasis, 931 Nephrolithotomy, 967 Nephroliths. See under Urolithiasis Nephropathy. See also Renal disease(s) diabetic, 214 feline immunodeficiency virus-associated, XIII:286 from hypercalcemia, 346 hereditary, X-linked inheritance of, XIII:910t Nephrostomy percutaneous, 965-966, 966f catheter placement, 933 Nephrotic syndrome hyperkalemia and hyponatremia with, XIII:375 risk for pulmonary thromboembolism, 696

1372

  Index

Nephrotomy, 934-935 indications for, XIII:866-868 (See also EVOLVE) Nephrotoxic drugs. See Drug toxicity Nephrotoxins, XIII:212-216 chemotherapy drugs as, 308-309 diagnosis and treatment of, 159-164 iohexol as, 871 list of, 160b, 161b, 855-856, 856b Nerve biopsy(ies), for dysphagia, 480-481 Nerve blocks, 14-16 Nerve sheath tumors, nasal and paranasal, XIII:501t Nervous system infections retroviral, XIII:288-291, XIII:289t use of glucocorticoids with, 1231 Netilmicin, toxicity of, 162, XIII:214 Neuroblastoma, nasal and paranasal, XIII:501t Neurocardiogenic syncope, 709-710, 710b, 711t Neuroepithelial tumors, 1080 Neurologic disorder(s) atlantoaxial subluxation, 1083-1087 autoimmune myasthenia gravis, 1108-1111 canine cervical spondylomyelopathy, 1088-1093 causing anisocoria, 1172-1174 causing seizures, 1062-1069 cerebrovascular disease and, 1074-1077 Chiari-like malformation, 1102-1107 degenerative lymphosacral stenosis, 1094-1096 dysautonomia as, XIII:957-959 encephalitis and meningitis, 1070-1074 feline immunodeficiency virus-associated, XIII:286 hypothyroidism and, XIII:327, XIII:974-975 intracranial tumors causing, 1078-1083 neuropathies, 1114-1116 physical therapy and rehabilitation for, 1131-1135, 1134b, 1135b pituitary tumors causing, XIII:367 syringomyelia, 1102-1107 vestibular disease causing, 1097-1101 Neurologic examination, for craniocerebral trauma, XIII:179-180 Neuromuscular disease dysphagia from, 479-480 megaesophagus from, 487b, 488 respiratory acidosis and, 58b Neuron dysfunction, from dysautonomia, XIII:957-959 Neuropathy(ies) chronic inflammatory demyelinating, XIII:982-985, XIII:982t-983t diabetic, 214-215 from arterial thromboembolism, 819-820 peripheral, associated with hypothyroidism, XIII:327 (See also EVOLVE) treatment of, 1114-1116 Neuroprotective agents, for stroke, 1076 Neutering, early age, 1019-1024 Neutropenia antimicrobial therapy and, XIII:267-272 differential diagnosis of, XIII:105t from chemotherapy, 307-308 from methimazole, 175 Neutrophil(s). See also Neutropenia; Neutrophilia deficiencies, XIII:519 dysfunction, XIII:447-451 (See also EVOLVE) effect of granulocyte colony-stimulating factor on, XIII:405 function of, XIII:447-448, XIII:450-451 (See also EVOLVE) Neutrophilia differential diagnosis of, XIII:105t role of glucocorticoids on, 402 Neutrophilic cholangitis, 576-579 Neutrophilic keratitis, XIII:1072 Nevi, 1156 Newberyite, compound uroliths with, XIII:876t Newfoundland dogs, subaortic stenosis in, 757-761

Niacinamide for episcleritis, in dogs, 1191t, 1192 use of, in dermatology, XIII:537 Nicoderm ingestion, 136 Nicorette ingestion, 136 Nicotine replacement products, 135-136, 136t Nicotine toxicity, XIII:230 and content in tobacco, 136t diagnosis and treatment of, 135-138 sources of, 136t Nictitating membrane causing red eye, 1175, 1176f neoplasia of, 1156 Nitenpyram toxicity, 123-124 Nitrofurantoin causing polyneuropathy, 1115 for urinary tract infections, 1226, 1226t Nitrogen balance, urine collection to determine, XIII:13t Nitroglycerin ointment for feline cardiomyopathy, 811t, 813 for heart failure, 774-776, XIII:765 Nitroprusside, XIII:194-197, XIII:194f, XIII:195f. See also EVOLVE for heart failure, 774-776 for noncardiogenic pulmonary edema, 665 Nitrosoureas, XIII:470-471, XIII:474 Nizatidine (Axid), XIII:615t, XIII:617 toxicity of, XIII:229 Nocardia spp., pyothorax from, 677, XIII:821 Noncardiogenic pulmonary edema, 663-665 Nonepitheliotropic cutaneous lymphoma, immunophenotyping for, XIII:507-508 Nonspherocytic hemolytic disorders, XIII:417t Nonsteroidal antiinflammatory drug(s) (NSAIDS) adverse effects of, 855, 856b as antiplatelet therapy, 24-25 causing gastric ulceration, 498-500, 499f causing liver disease, 568t, 569 causing nephrotoxicity, 160b, 162 effect on thyroid function, 187t for anterior uveitis, 1205, 1206t for bladder cancer, 371 for feline idiopathic cystitis, 948 for hip dysplasia, 1123-1124 for neurologic and musculoskeletal pain, 1128t, 1129-1130, 1129f for ocular diseases, 1151-1152, 1151t for osteoarthritis, XIII:1019 for pain management, 12f, 14, XIII:61 toxicity of, 97t, XIII:214-215, XIII:227-229 Nonsteroidal immunosuppressive therapy, for dermatology, XIII:536-538 Norepinephrine (Levophed) for hypotensive shock, 6 use of, in gastric dilatation-volvulus, 78 Normal sinus rhythm, in cats, 733-734, 734f Norwegian method, 985 Nosocomial infection(s) bacterial resistance and, XIII:262-267 prevention of, XIII:261 septic abdomen, 74 Nosodes, for feline retrovirus, 1281t Notoedres mites differential diagnosis for, XIII:565t skin scraping for, XIII:526 NSAIDS. See Nonsteroidal antiinflammatory drug(s) (NSAIDS) Nuclear scintigraphy. See Scintigraphy Nursing care, physical therapy and rehab as, 1131-1135 Nutraceutical(s) for heart disease, XIII:714 for heart failure, 773, 779t for osteoarthritis, XIII:1020-1021 Nutrient(s) comparison of dry matter and energy basis of, XIII:75t in diabetic diets, 206-207 interactions of with ACE inhibitors, XIII:712-713 with diuretics, XIII:712 with drugs, XIII:712

Nutrient(s) (Continued ) profiles, of multiple diets for treatment of urinary tract disease, XIII:844t-845t requirements of, XIII:73-74 Nutrition. See also Anorexia; Dietary therapy; Food allergy; Percutaneous gastrostomy (PEG) tube(s) AAFCO nutrient profiles for, 1337-1340 adequacy statements of, XIII:76-77 after gastric dilatation-volvulus, XIII:168-169 assessment of food labels for, XIII:74-80 in the cancer patient, XIII:459-460 effect of on bacterial translocation, XIII:201-202 on urine crystal formation, 850-851 enteral (See also Enteral nutrition; Microenteral nutrition) feeding methods for, XIII:72t evaluating caloric need for, in cats, XIII:688 feeding neonates and, XIII:625-626 feeding tubes, 23 esophageal, 589-593, XIII:597-599 techniques for, 590f, 591f, 592f, 593f tube management, 592-293 for esophageal disease, 484-485, XIII:609 for hepatic lipidosis, 572 for pancreatitis, in cats, 539-540, XIII:702t gastrostomy complications of, 908 in kidney disease, 906-910 tube management, 907-908 tube placement, 907-908 for acute renal failure, XIII:177 for diarrhea, XIII:653-658 for heart disease, XIII:711-716 for parvoviral enteritis, XIII:630 for small intestinal bacterial overgrowth, XIII:640-641 homemade diets as, for liver disease, XIII:696t hypoallergenic diets and, XIII:530-536 (See also EVOLVE) in craniocerebral trauma, XIII:184-185 in critical care, 18-23, XIII:201-203 in cats, XIII:104 in heart disease, 704-708 in the cancer patient, XIII:458-462 (See also EVOLVE) liver disease and, XIII:693-697 management of diarrheal diseases and, XIII:653-658 microenteral, XIII:136-140 (See also EVOLVE) obesity and, 193-194 parenteral (See Parenteral nutrition) percutaneous gastrostomy tube for (See Percutaneous gastrostomy (PEG) tube) peritoneal dialysis and, XIII:860 pet food safety and, XIII:236-238 (See also EVOLVE) protein-restricted, effect of, on liver, XIII:668t recommendations, for urinary diseases, XIII:841-846 related causes of Heinz bodies, XIII:421-422 requirements during pregnancy and ­lactation, 1003-1008, 1007f routes of support for, XIII:71-74 shock and, 7 Nutritional imbalances causing pregnancy loss in bitches, 988 in queens, 1044 in homemade diets, 167 Nutritional supplements, for food allergy, 396 Nystagmus, from vestibular disease, 1097, XIII:967 Nystatin for Pythium spp. infections, XIII:314 otic therapy, 431t O o,p’-DDD therapy. See Hyperadrenocorticism; Mitotane

Obesity and tracheal collapse, XIII:799 chronic bronchitis and, XIII:804 diagnosis and treatment of, 191-195, 192b effect of early neutering on, 1021-1022 on blood pressure, XIII:839 on heart, XIII:711-712 in feline diabetics, 207-209 nutritional management of, XIII:711-712 Obsessive-compulsive disorder, acral lick dermatitis and, 472-473, XIII:555 Obstetrical mutation, for dystocia, XIII:936-937 Obstipation. See Constipation Obstruction, urinary. See also Feline lower urinary tract disease; Urethral obstruction; Urolithiasis treatment of, XIII:849-850 ureteral, XIII:868-870 urine diversion for, by tube cystostomy, XIII:870-871 Obstructive, causes of neonatal diarrhea, XIII:627t Occipital hypoplasia, from syringomyelia and Chiari-like malformation, 1102-1107 Octreotide (Sandostatin) for chylothorax, 680 for gastrinoma, XIII:619 for insulinoma, XIII:360-361 Ocular anomalies, causing retinal detachment, 1215 complications in diabetic pets, 215 emergencies, XIII:1090-1094 (See also EVOLVE) exposure to toxins, 112 feline herpesvirus infection, XIII:1057-1060, XIII:1074 (See also EVOLVE) foreign bodies, XIII:1072 immunotherapy, 1149-1153 inflammatory cascade, 1149-1150 neoplasia, 1153-1158, XIII:1094-1097, XIII:1094t redness, 1175-1178 surface, drug therapy for, 1145-1146 Ocular disease. See under Ophthalmic Ocular pharmacology, 1145-1149 Oculomotor nerve, anisocoria from lesion of, XIII:1048t Oculomycosis. See under Fungal infection Oil of Wintergreen toxicity, 123 Ointments, as tear substitutes, XIII:1064t Old English sheepdog(s), avermectin toxicosis in, 125-127 Oligozoospermia, 1049-1052 Oliguria definition of, XIII:14t in acute renal failure, XIII:175-176 treatment of, XIII:849 with acute kidney failure, 879-881, 880t Olsalazine (Dipentum), for chronic colitis, 518-519, 519t Oseltamivir (Tamiflu), 1293 Oltipraz, for aflatoxicosis, 158 Omentalization, for chylothorax, 682 Omeprazole (Prilosec) for acute renal failure, 881 for drug-associated liver disease, 569 for esophageal disease, 484, XIII:609 for gastric ulceration, 500 for gastrointestinal disorders, due to shock, XIII:144 for uremic gastropathy, 916 use of, during shock, 7 Oncology clinical trials in, 297-300, 298t surgical principles of, 320-324 Ondansetron (Zofran) for vomiting cats, 574 with acute renal failure, 881 with chemotherapy, 308 Onion ingestion, 110 Open peritoneal drainage. See Peritoneal drainage

  Index Ophthalmic disease(s), 1140-1145. See also under Eye; specific disorders anisocoria, causes of, 1168-1174 anterior uveitis, 1200-1207 antiviral drugs for feline herpes, 1188-1190 associated with hypothyroidism, XIII:328 blindness, causes of, 1163-1167 drug pharmacology for, 1145-1149 emergencies causing, XIII:1090-1094 (See also EVOLVE) episcleritis, in dogs, 1190-1192, 1191t eyelid and periocular skin diseases, 11781184 feline chlamydiosis, 1185-1187 feline glaucoma, 1207-1214 immunotherapy for, 1149-1153 inflammatory, nonspecific therapy for, XIII:276t manifestations of systemic infectious disease as, XIII:276 (See also EVOLVE) neoplasia, 1153-1158, 1154f nonhealing corneal ulcerations, 1197-1200 red eye, causes of, 1175-1178, 1176f retinal detachment, 1215-1219, 1217f scleritis, in dogs, 1190-1192 tear film disturbances causing, 1193-1196, 1194f, 1195f Ophthalmic examination changes, with craniocerebral trauma, XIII:179 corneal colors as diagnostic aid for, 1158-1163 pearls of the, 1140-1145 with ophthalmoscope, direct and indirect, 1143 Opioid(s) cocktail, for pain management, 11-12 dosage guidelines for, XIII:59t epidural, XIII:127-128 for acute pain management, 11-12, 11t, 88-89 for feline idiopathic cystitis, 948 for neurologic and musculoskeletal pain, 1128t, 1130 side effects of, XIII:123 toxicity of, 145-146 use of, XIII:123 Opisthotonos, XIII:179 Optic nerve, disease of atrophy of, XIII:1040 causing blindness, 1166 blindness from, XIII:1040 causing anisocoria, 1172-1173, XIII:1048-1049 optic chiasm, anisocoria from lesion of, XIII:1048t Optic neuritis causing blindness, 1166 causing mydriasis, 1171 Optic radiation, anisocoria from lesion of, XIII:1048t Optic tract, anisocoria from lesion of, XIII:1048t Optivisor head loupe, 1140 Oral examination, in the cat, XIII:600 Oral inflammatory disease, feline, XIII:600-602 Oral papillomas, canine, 444, XIII:569 Oral tumor(s). See also under Neoplasia melanoma, 378-380 radiation systems for, XIII:482-485 radiotherapy for, 318 Orbifloxacin (Orbax) for Pseudomonas spp. aeruginosa, XIII:264 minimum inhibitory concentrations (MIC) for, XIII:42t tissue concentrations of, XIII:45t use and misuse of, XIII:41-48 Orbit, diseases of abscess, XIII:1087 anisocoria from lesion of, XIII:1048t causing exophthalmos, XIII:1086-1089 (See also EVOLVE) cellulitis, XIII:1087 neoplasia, 1153-1158, 1154f

1373

Orchiepididymitis, XIII:944-945 Organ failure, from sepsis, XIII:275 Organophosphate toxicity, 114t, 115, XIII:231-233 association with pancreatitis, 701, XIII:697 diagnosis and treatment of, 119-121, 120b Orlistat (Xenical), 194 Ormetoprim-sulfadiazine, associated liver disease, 568t Ormetoprim-sulfadimethoxine (Primor) adverse reactions of, in dogs, XIII:240t for neutropenia, XIII:269t Orogastric decompression, 80 Oropharyngeal dysphagia, 479-482, 479t Orphan(s) feeding of, XIII:626 vaccine recommendation with, XIII:255 Orthopedic disorder(s), associated with obesity, 192b Orthopoxvirus, 442-443 Orthovoltage units, XIII:482 Ortolani sign, 1121-1122 Os clitidoris, 1014-1015, 1015f Oslerus (Filaroides) osleri, 667-668, 667f, 668f Osmolality definition of, XIII:116 of urine, estimate of, XIII:325 Osmolarity, of colloid fluids, 63t Osmotic drugs, ophthalmic drug reactions to, osmotic agents, for glaucoma, XIII:1077-1078 Osmotic fragility, XIII:417t, XIII:419 Ossification, incomplete, of humeral head, of dogs, XIII:1000-1004 Osteoarthritis chondromodulating drugs for, XIII:1018-1022 hip, 1120-1125, 1124t treatment of, XIII:1018-1022 with heart failure, 779 Osteochondritis dissecans, of the humeral condyle, XIII:1006-1014 Osteochondrosis, elbow dysplasia as, XIII:1004 Osteoclastic resorptive lesion, stomatitis and, in cats, XIII:601-602 Osteomyelitis, empiric antimicrobial therapy for, 1228-1229 Osteosarcoma chemotherapy protocols for, 361t diagnosis and treatment of, 358-362 nasal and paranasal, XIII:501t of the larynx and trachea, XIII:503t orbital, 1154, 1154f OtiCalm, 430t OtiClens, 430t OtiFoam, 430t Otitis externa. See also under Ear causing hearing loss (See Deafness) chronic recurrent, 432-433 Malassezia, 453-457, 455t glucocorticoid use for, XIII:586 Pseudomonas, therapy of, XIII:264, XIII:586-588, XIII:587t therapy of ear flushing techniques for, 436-438, XIII:583-584 systemic, 434-436 topical, 428-433, 430t, 431t, 432t, 433b with glucocorticoids, XIII:585-586 Otitis interna causing hearing loss (See Deafness) vestibular dysfunction from, XIII:968 Otitis media causing vestibular disease, 1098 systemic therapy for, 434-436, 455t, 456 with Pseudomonas aeruginosa, XIII:264 Otoacariasis, vector associated with, XIII:297t Otobius megninii, as vectors, XIII:297 Otoclean, 430t Otodectes cyanotes. See Ear mite(s) Ototoxicity, topical, 432, 433b Ovarian remnant syndrome, in cats, 1040-1041

1374

  Index

Ovariohysterectomy causing urinary incontinence, 1021 early age, 1019-1024 for pyometra, 1009 ovarian remnant syndrome from, in cats, 1040-1041 with mammary cancer, 365 Ovulation in dogs, 974-975, 975t, 976f, 978f insemination and, XIII:916 timing of parameters, XIII:927t progesterone for, XIII:914-915 Oxacillin for pyoderma, 1226t, 1227 intravitreal, 1148t subconjunctival, 1147t Oxalobacter formigenes, 931 Oxatomide, for feline pruritus, 408, XIII:544t Oxibendazole, associated liver disease, 568t Oximetry. See Pulse oximetry Oxybutynin chloride (Ditropan) for feline idiopathic cystitis, 948, XIII:889t, XIII:891 for lower urinary tract disease, XIII:900t, XIII:901 for urinary incontinence, 957t, 959 Oxygen cages, for oxygen delivery, 599-600 delivery oxygen consumption and, 3f principles of, 596 shock and, 2-3 equilibrium curve for, with Oxyglobin, XIII:425f of tissues, in sepsis, XIII:273-274 saturation, 3-4, 596 Oxygen radical scavengers, in sepsis, XIII:274 Oxygen therapy, 596-603 for craniocerebral trauma, XIII:182-183 for noncardiogenic pulmonary edema, XIII:811 for patients requiring transport, 601 for tracheal collapse, 633 hyperbaric, 601-602, 602b in cats, XIII:100-101 indications for, 597b patients not responding to, 600-601 principles and techniques of, 596-603, 597b toxicity from, 664 Oxyglobin (Biopure), 64, 65t, XIII:424-427 as blood alternative, 265 characteristics of, 63t for anemia with chronic kidney disease, 917-918 for disseminated intravascular coagulation (DIC), 290 for immune-mediated hemolytic anemia, 269 success rates of, XIII:425f Oxymorphone epidural, XIII:127-128, XIII:127t for neurologic and musculoskeletal pain, 1128t for pain management, 11, 11t, 12f-13f, XIII:59, XIII:59t use of, XIII:123, XIII:125t Oxypolygelatin, XIII:133, XIII:133t Oxytocin for agalactia, 1001 for dystocia, in dogs, 997, XIII:937 for postpartum hemorrhage, 1000t Ozagrel hydrochloride, for feline infectious peritonitis, 1297t P P-Glycoprotein, XIII:479-480 Pacemaker(s) external, 43-47 for bradyarrhythmias, XIII:722f, XIII:725 for syncope, 712t indications for temporary, 44b permanent cardiac, in dogs, 717-721, 718t, 719f-720f temporary, 43-47, 720-721 transvenous pacing before, XIII:197-200

Paclitaxel (Taxol), 312t, 313, 313b, XIII:475 Pain clinical characteristics of, 1127t local and regional treatment of, 14-16 management of, 9-17, 12f-13f, XIII:57-61 for acute abdomen, 71 for musculoskeletal disorders, 1126-1131, 1127t for spinal disorders, 1126-1131 in cats, XIII:105 nomenclature describing, 1127t pathophysiology of, XIII:57-58 scoring of, 9-10, 10b Paint ingestion, 127, 134 Paint thinner toxicity, 134 Paintball toxicity, 141-142 Palisading granuloma, 464 Palpation abdominal, 69 for pregnancy diagnosis, in dogs, XIII:918-919 Pamidronate for anal sac tumors, 384 for hypercalcemia of malignancy, 346f, 347 for osteosarcoma, 362 Pancreas, disease(s). See also Pancreatitis abscess, in cats, 542, XIII:705 adenoma of, 542 atrophy of, 531 exocrine in cats, 538-543, XIII:701-705 in dogs, 531-534 pancreatic enzyme (Viokase), for cats, XIII:703 in dogs, 534-538 pancreatic bladder, 542, XIII:704 pancreatic enzyme (Viokase), for pancreatitis, XIII:700 parasites, in cats, 542, XIII:705 pseudocyst, in cats, 542, XIII:705 Pancreatic enzyme (Viokase) supplementation for EPI in cats, 541 in dogs, 532-533 for flatulence, 526 for pancreatitis, 537 Pancreatic lipase immunoreactivity, 535 Pancreatitis acute effect of, on liver, XIII:668t, XIII:669-670 nutritional management of, XIII:657 and acute abdomen, 71 complications of, XIII:700 diagnosis and treatment of in cats, 538-543, XIII:701-705 in dogs, 534-538, XIII:697-700, XIII:698 diets for tube feeding cats with, XIII:702t epidural anesthesia and analgesia for, 15-16 post-operative, after insulinoma, XIII:359 risk for pulmonary thromboembolism with, 696 risk of, in canine diabetes mellitus, 206 role of, in feline diabetes mellitus, 200 use of lipids in, 19 with biliary mucocele, 589 with diabetes mellitus, 215 with feline inflammatory liver disease, 578 Pancytopenia cytograms and histograms of leukocytes demonstrating, XIII:386f from estrogen, 147-148 Panleukopenia causing neonatal diarrhea, XIII:626 control of, in catteries, 1300t, 1304-1305 thrombocytopenia from, XIII:441t vaccination for, 1275, 1276t, XIII:250 Pannus, XIII:1067 Pantheline (Pro-Banthine), 948 Pantoprazole for gastric ulceration, 500 use during shock, 7 Panuveitis, 1202 retinal detachment with, 1216 Papillomas, adnexal, 1154, 1183

Papillomaviruses canine diagnosis and treatment of, 443-446 squamous cell carcinoma from, 445 treatment of cutaneous lesions, 424 feline, treatment of cutaneous lesions, 442 Paracentesis anterior chamber, 1202, 1203f vitreous, 1203, 1204f Paragonimus kellicotti, 670-671 Parainfluenza, vaccination recommendations for, XIII:250 Paramunity induces, for feline retrovirus, 1280 Paranasal sinuses, tumors of, XIII:501-502, XIII:501t Paraneoplastic syndrome hypercalcemia, 343-347, 929-930 with renal neoplasia, 929-930 Paraquat, causing nephrotoxicity, 160b Parasite(s) causing blepharitis, 1179-1180 causing encephalitis and meningitis, 1071-1072 causing heartworm disease in cats, 831-837 in dogs, 837-842 causing myocarditis, 805t causing neonatal diarrhea, XIII:626-627, XIII:627t during pregnancy, in dogs, XIII:932 feline demodicosis, 438-440 nasal, 610, 610b, 624 respiratory, 666-671 treatment of, 1335t-1336t Parasiticide toxicosis, 125-127 Parasympathetic, lesions, causing anisocoria, XIII:1049-1050 Parathyroid hormone (PTH) evaluation of with hyperparathyroidism, 249, XIII:347 with hypoparathyroidism, 241-243, XIII:340 with idiopathic feline hypercalcemia, 236 with paraneoplastic hypercalcemia, 344-345 monitoring with chronic kidney disease, 893-895 replacement therapy, 243 role of, in calcium homeostasis, 344t, 892-893 Parathyroid hormone-related protein (PTHrP), 249 role of, in paraneoplastic hypercalcemia, 344-345, 344t, 929 Parenteral nutrition, 18-22 bacterial translocation and, XIII:202-203 complications of, XIII:87-89 for anorexia, XIII:72-74 for gastric dilatation-volvulus, XIII:168-169 for the cancer patient, XIII:461-462 guidelines for, XIII:89 partial, for parvoviral enteritis, XIII:630 products for, XIII:80-84 with gastric dilatation-volvulus, 82 worksheet for calculating, 21b-22b Paresis, in cats, with Borna disease, XIII:976-978 Parotid duct transposition, XIII:1065 Paroxetine HCl (Paxil), for acral lick dermatitis, 473, XIII:555 Paroxysmal atrial tachycardia, 722 Pars planitis, 1201, 1202f Partial parenteral nutrition. See Parenteral nutrition Partial thromboplastin time (PTT) during heparin therapy, 693-694, 694t in disseminated intravascular coagulation, XIII:192 in rodenticide toxicosis, 117-118 Parvovirus infection. See also EVOLVE causing neonatal diarrhea, XIII:626 causing nonregenerative anemia, 272-273 causing pregnancy loss, 987 clinical signs of, XIII:629t

Parvovirus infection (Continued ) diagnosis of, XIII:11, XIII:630 feline, 1300t, 1304-1305 (See also Panleukopenia) granulocyte colony-stimulating factor and, XIII:405 laboratory abnormalities, XIII:629t microenteral nutrition for, XIII:138 myocarditis from, 807 polymerase chain reaction for, XIII:248 prevention of, XIII:631-632 risk with early age neutering, 1020 therapy of, XIII:271, XIII:631t thrombocytopenia from, 282t, XIII:440, XIII:441t transmission of, XIII:629-632 vaccine recommendations for, 1272, 1273t, XIII:250 Pasteurella multocida rhinitis, 610, 610b, 613 Patches, nicotine, 135-138, 136t Patent ductus arteriosus (PDA) cardiac catheterizations for, XIII:742-744, XIII:743f clinical findings with, in cats, XIII:739t diagnosis and treatment of, 744-747, 745f, 746f surgery for, XIII:745 therapy of, in cats, XIII:740t Pathology diagnostic and sampling strategies for, XIII:452-458 for diagnosis of acute abdomen, 69-70 Pediatric medicine. See Neonatal medicine Pediculus, differential diagnosis for, in cats, XIII:565t PEG tube. See Percutaneous gastrostomy (PEG) tube Pegylated liposomal doxorubicin. See Doxorubicin Pelger-Huët anomaly, XIII:449t, XIII:450 Pelodera larvae, skin scraping for, XIII:526 Pelvic canal, narrowing of, XIII:1030 Pelvic fractures, XIII:1026-1032, XIII:1027f-1028f Pelvic osteotomy, for megacolon, XIII:652 Pelvic trauma, XIII:1027f sacral fractures and sacrococcygeal injuries and, XIII:1023-1026 surgical considerations for, XIII:1030-1031 Pemphigus erythematosus causing blepharitis, 1182 topical immune modulators for, 422 Pemphigus foliaceus causing blepharitis, 1181-1182 drug eruptions similar to, XIII:558 Pemphigus, nonsteroidal immunosuppressive therapy for, XIII:536 Penciclovir, for feline herpesvirus, 1189 Penicillamine for copper-associated hepatitis, 561 for lead toxicity, 129 Penicillin(s) for leptospirosis, XIII:309 penicillin G minimum inhibitory concentrations (MIC) of, XIII:35t spinal cord damage from, 111 Penicillium spp., causing rhinitis, 613-614 Penis effect of early neutering on, 1020-1021 intermittent erection in male castrated dogs, 1053 PennHIP, 1122 Pennies ingestion, 110 Pennyroyal oil toxicity, 120b, 123, 152t, 153 Pentamidine isethionate, for pneumocystosis, 1260 Pentasa, 519 Pentastarch, 64-66, XIII:133t characteristics of, 63t use of, in gastric dilatation-volvulus, 78 Pentazocine (Talwin), for pain management, XIII:59t

  Index Pentobarbital adverse reactions of, in dogs, XIII:240t for mechanical ventilator support, 607 for strychnine toxicosis, 118 Pentosan polysulfate for feline idiopathic cystitis, 947t, 949 for feline lower urinary tract disease, XIII:889t for osteoarthritis, XIII:1020 Pentoxifylline (Trental) in dermatology, XIII:537 use, dosage and adverse reactions to, 397-400 Peptic ulcers. See Gastric ulceration Pepto Bismol, for Helicobacter spp. infection, 495-496, 495f Percussion, abdominal, 69 Percutaneous gastrostomy (PEG) tube(s). See also Nutrition anesthesia for placement of, XIII:85 devices for, XIII:84-87 for esophageal disease, XIII:609 for hepatic lipidosis, XIII:687-690 guidelines for use with, XIII:696t in cats, XIII:688-690 placement of, XIII:84-87 removal of, XIII:86-87 vomiting with, XIII:689 Perfusion, monitoring of, during shock, 2-4 Perianal adenoma, 528 Perianal fistulas anal sacculectomy and, XIII:593 cyclosporine for, 255, 468 therapy of, 467-468, 528-529 topical immune modulators for, 423 Pericardectomy for chylothorax, 680 for pericardial effusion, 829-830 Pericardial disease, causing chylothorax, 678 Pericardial effusion diagnosis and treatment of, 825-831, 827f, 828b, 828f, 829f, XIII:772-777 hyperkalemia and hyponatremia with, XIII:375 surgery for, XIII:775 Pericardial fluid analysis, XIII:774-775 Pericardiocentesis, 827-828, 828b, 828f, 830, XIII:775 Pericardotomy, for open chest cardiopulmonary resuscitation, XIII:148 Periodontitis, with stomatitis and faucitis, XIII:600 Perineal hernia, 529-530 Periodontal disease. See Dental disease Periodontitis, Porphyromonas spp. vaccine for, 1274 Periosteal proliferation, from hepatozoonosis, XIII:311 Peripheral nerve disease differential diagnosis for, in dogs, XIII:984 from chronic inflammatory polyneuropathy, in dogs, XIII:982-985 from hypothyroidism, 185-186 Peripheral nerve injury, rehabilitation considerations for, 1135 Peripheral venous catheters, 38 Peritoneal dialysis, XIII:859-861. See also EVOLVE for ethylene glycol toxicity, 132 Peritoneal drainage, 72-76, 74f, 76t Peritoneal effusion hyperkalemia and hyponatremia with, XIII:375 in feline infectious peritonitis, XIII:291 Peritoneal lavage, diagnostic, XIII:162-163 Peritonitis bile, 588-589 diagnosis of, 71 differential diagnosis of, with acute abdomen, 68t epidural anesthesia and analgesia for, 15-16 evaluation of, 74b septic, local vs. generalized, 73 Periwinkle, 151t Perlutex, 1028

1375

Persian cat(s), Chédiak-Higashi syndrome in, XIII:450 Persistent müllerian duct syndrome. See Müllerian duct syndrome Pesticide(s) causing nephrotoxicity, 160b exposure to, 93 incidence of poisoning, XIII:206t pet food safety and, XIII:236 Pet food contamination of, XIII:238 recall, 165-158 regulation, 166 safety, XIII:236-238 (See also EVOLVE) Pet identification, and retrieval systems, XIII:93-95 Petrolatum (Laxatone; Petrolatum), for constipation, in cats, XIII:651t Petroleum distillates, toxicity of, XIII:225-226 PGF-2 α(Lutalyse) adverse effects of, 1009 for canine pregnancy termination, 1031-1032 for metritis, 1000, 1000t for pyometra, 1009 pH. See also Blood pH of colloid fluids, 63t where urine crystals are found, 850, 851t Pharmacokinetics drug monitoring and, XIII:27-31 of quinolones, XIII:41-45 Pharmacotherapy, for obesity management, 194-195 Pharmacovigilance, 99-104 Phenacetin, Heinz body anemia from, XIII:421 Phenazopyridine as urinary tract analgesic, XIII:891 Heinz body anemia from, XIII:421 Phenobarbital associated liver disease, 568t drug monitoring of, XIII:28t effect of on liver function and enzymes, 545, 550, 568t on thyroid function, 187t for seizure disorders, in dogs, XIII:960, XIII:961t for seizures from intracranial tumors, 1079t, 1082 for sensory mutilation, XIII:91, XIII:92t for status epilepticus, 1063f, 1064 in cats, XIII:965 in traumatic brain injuries, 35t loading dose for, 1063f monitoring of serum, in dogs, XIII:960 toxicity of, XIII:217 Phenols as disinfectant, XIII:259 toxicity of, XIII:224 Phenothiazine(s), interaction of, with metoclopramide, XIII:615 Phenotypes, of histiocytic proliferative diseases, XIII:588 Phenotypic sex, 1034, 1036t, 1037-1039, XIII:904, XIII:905t Phenoxybenzamine for feline lower urinary tract disease, XIII:889t, XIII:891 for urethral spasms post urethral obstruction, 954 for urinary retention, 955, 956t Phentolamine, for canine retrograde ejaculation, 1050 Phenylbutazone, toxicity of, 162, XIII:214-215 Phenylephrine for anterior uveitis, 1206t for evaluating anisocoria, 1174 for evaluating red eye, 1175 for hypotensive shock, 6 for urinary incontinence, 958 toxicity of, XIII:153-157 Phenylpropanolamine for canine retrograde ejaculation, 1050 for feline lower urinary tract disease, XIII:889t

1376

  Index

Phenylpropanolamine (Continued ) for urethral sphincter incompetence, XIII:898 for urinary incontinence, 957t, 958 for vaginitis, 1011 toxicity, XIII:153-157 Phenytoin (Dilantin) adverse reactions of, in dogs, XIII:240t associated liver disease, 568t toxicity of, XIII:217 Pheochromocytoma adrenal, XIII:369 causing hypertension, 714, 714t, 716 polyuria and polydipsia from, 847t urine collection for, XIII:13t Pheromone, feline facial, 950 Phosphate binders, for progressive renal failure, XIII:862-863 Phosphodiesterase-5 inhibitors, for pulmonary hypertension, 701 Phosphofructokinase deficiency, XIII:416t, XIII:419 autosomal recessive inheritance of, XIII:910t genetic test for, 1056t Phosphorus. See also Hyperphosphatemia; Hypophosphatemia dietary, and renal failure, 873t, 875, 889t, 892-893, XIII:862 monitoring with calcitriol therapy, 894-895 overview of metabolism with calcium, 892-893 supplementation in fluid therapy with diabetic ketoacidosis, 217b with hepatic lipidosis, 574 Phosphorus 32 (32P), XIII:485 Phosphorus-containing urinary acidifiers, toxicity of, 160b Photodynamic therapy (PDT), for bladder cancer, 372 Phycomycosis. See Pythium spp.; Skin Physical therapy and coupage, for airway management, XIII:791-792 for hip dysplasia management, 1124-1125, 1124t for neurologic and musculoskeletal pain, 1130 for neurologic patients, 1131-1135, 1134b, 1135b for pain management, 12f, 17 for pneumonia patients, 662 Physostigmine, for evaluating anisocoria, 1173 Phytosphingosine shampoo, 411t, 412-414, 412t, 414t Pigmented plaques, papillomavirus-associated, in dogs, XIII:570 Pilocarpine for dysautonomia, XIII:958 for evaluating anisocoria, 1173 for feline glaucoma, 1210t, 1211 for glaucoma, XIII:1093 for keratoconjunctivitis sicca, XIII:1062 Pimecrolimus, 423 safety concerns of, 423-424 Pimobendan (Vetmedin) for aortic thromboembolism, 814 for cardiogenic shock, 777 for dilated cardiomyopathy, in dogs, 795 for Doberman pinscher cardiomyopathy, 803 for feline cardiomyopathy, 811t, 814, 818 for heart failure, 772-775, 779t, 784 for myocarditis, 806 for ventricular septal defect, 750 Pind-avi/Pind-orf, for feline retrovirus, 1280, 1281t Pine oil, toxicity of, XIII:224 Piperacillin, minimum inhibitory ­concentrations (MIC) of, XIII:35t Piperonyl butoxide, 121 Pirbuterol toxicity, XIII:154, XIII:154t Piroplasma infections, 1288-1291, 1289t Piroxicam as chemotherapy, XIII:476 as palliative therapy for cancer, XIII:477 causing nephrotoxicity, 162 for bladder cancer, 371-372

Piroxicam (Continued ) for feline lower urinary tract disease, XIII:889t, XIII:892 for idiopathic rhinitis, 615, 618 for melanoma, 380 for osteoarthritis, XIII:1019 nasopharyngeal tumors, 626 toxicity of, XIII:227 Pituitary gland tumors, XIII:366-368. See also EVOLVE microadenomas, 1080 radiation therapy of, XIII:367-368 Pituitary-adrenal function, effect of nonadrenal disease on, XIII:362-363 Plague, thrombocytopenia from, 283t Plant poisoning, incidence of, XIII:206t Plant(s) and herbal toxicities, 149-156, 151t Brunfelsia spp., 140-141 nephrotoxic, 163, 856b nontoxic, XIII:220-221t toxic exposure to, 95-99, 97t toxic ornamental, XIII:216 Plaque, control of, 477-478 Plasma. See also Laboratory characteristics of, 63t comparison of, to synthetic colloids, XIII:132t effect of Oxyglobin on, XIII:426 Plasma cell leukemia. See Myeloma, multiple Plasma colloid osmotic pressure (COP), 61-64 Plasma protein(s) colloid therapy and, XIII:66 for pregnancy diagnosis, in dogs, XIII:922-923 Plasma transfusion, XIII:402 for coagulopathies, 280 for disseminated intravascular coagulation, 290-291, XIII:193 for hereditary coagulopathies, XIII:437 for hypoproteinemia, 514 for pancreatitis, 537, 540, XIII:699 in cats, XIII:702 for platelet dysfunction, 295-296 for shock therapy, 5, XIII:142 for von Willebrand’s disease, 278-279 in cats, XIII:445-446 Plasmacytic lymphocytic colitis, in dogs, XIII:643-645 Plasmacytoma, immunophenotyping for, XIII:508 Plasmagel (Urea-linked gelatin), XIII:67t Plasticizer, 132 Platelet(s). See also Thrombocytopenia activation of, XIII:443f cytograms and histograms of, XIII:384, XIII:387f interpretation of, XIII:381-390 (See also EVOLVE) dysfunction of, 293f, XIII:444, XIII:444t, XIII:445t antiplatelet therapy for, 24-27 diagnosis and treatment of, 292-297, XIII:442-447, XIII:443t diseases associated with, 293t, 294b drugs associated with, 294t with renal failure, 914 effect of hypothyroidism on, XIII:328 thrombopoietin on, XIII:407 estimate of, from blood smear, XIII:439 function of, 292, XIII:442 function testing of, 294, XIII:443-444 transfusion of, 295-296, XIII:402, XIII:445 guidelines for, 296t, XIII:446t Platinum compounds, as chemotherapy, XIII:469-470 Platinum drugs, 310 Platynosomum spp., 580 Plavix. See Clopidogrel Pleural effusion causes of, 676b, XIII:820t computed tomography for, XIII:710

Pleural effusion (Continued ) diagnosis and treatment of, 675-684 hyperkalemia and hyponatremia with, XIII:375 idiopathic, 684 in feline infectious peritonitis, XIII:291 medical and surgical management of, XIII:819-825 Pleural evacuation system, 687f Pleural space neoplasia, 354-355 Pleuritis, from chylothorax, 679-680 Pleurodesis, for chylothorax, 682-683 Pleuroperitoneal shunting, for chylothorax, 681-682 Pleurovenous shunting, for chylothorax, 681-682 Pneumomediastinum, 687 Pneumocystosis, diagnosis and treatment of, 1258-1260 Pneumonia. See also Specific microorganism and interstitial lung disease, 672, 673b aspiration from megaesophagus, 491 with laryngeal collapse, 629 with laryngeal paralysis, 627-628 bacterial, XIII:814t diagnosis and treatment of, 658-662, 659b, XIII:812-815 from Bordetella bronchiseptica, 646-647, 659-660 chronic bronchitis and, XIII:804 empiric antimicrobials for, 1226t, 1228 from pneumocystosis, 1258-1260 hydration and humidifications for, XIII:790-791 methods for reducing hospital acquired, 1224 nebulization for, XIII:791 ventilator-assisted, 608 Pneumonyssus caninum, 613, 624, 666-667 Pneumothorax, 87 diagnosis and treatment of, 685-689 from decortication surgery, 680 from esophageal perforation, 687 in dogs, XIII:825-827 open, 687 spontaneous, XIII:826-827 tension, 687 Pododermatitis, Malassezia, 454 Podophyllum peltatum, 151t Poikilocytosis, XIII:417t, XIII:423 Poinsettia ingestion, 111, XIII:220-221t Point-of-care laboratory testing, XIII:110-112. See also EVOLVE Poison control centers, 104-105, 112 Poisoning(s). See also Plant(s); Toxicity; specific agents (e.g. Ethylene glycol) exposures, 92-94, XIII:206, XIII:206t and treatments, 95-99, 96b, 96t from nephrotoxins, 159-164, 160b, 161b herbal product, 149-156, 151t, 152t, 154t insecticide, 119-125 legal considerations for, 105-108 sources of help for, 104-105 treatment of, 112-116, 114t, 116t, XIII:207-211, XIII:207t with common household chemicals, XIII:223-227 Pollakiuria, 944, 948-949 Polycythemia from renal tumors, 929 from right-to-left shunting, 751 polyuria and polydipsia from, 847t Polydipsia causes of, XIII:832t definition of, XIII:14t polyuria and, diagnostic approach to, XIII:831-834 primary, XIII:833 with diabetes mellitus, XIII:348 Polymer combinations, as tear substitutes, XIII:1064t

Polymerase chain reaction (PCR) diseases tested by, XIII:247t DNA and, XIII:246-247 for babesiosis, 1290 for brucellosis, 1235 for canine influenza, 1293 for ehrlichiosis, XIII:299-300 for feline calicivirus, 1286 for feline chlamydiosis, 1186 for feline coronavirus, XIII:292 for feline herpesvirus-1, 441, XIII:1058 for feline leukemia virus, XIII:281 for leishmaniasis, 1253 for leptospirosis, 859, 1238 for mycoplasmosis, 1247 for toxoplasmosis, 1256 for tritrichomonas, 510-511 single-round, XIII:248 Polymethylene polyphenol isocyanate toxicity, 140 Polymyopathy, hypokalemia and, in cats, XIII:985-987 Polymyositis, 1113 extraocular, XIII:1088, XIII:1090 Polymyxin B adverse reactions of, in cats, XIII:241t nebulization of, 662 Polyneuropathy, 1115. See also Neurologic disorder(s) chronic inflammatory demyelinating, in dogs, XIII:982-985 Polyoxygelatin (Vetaplasma), XIII:67t Polyps. See also under nasopharyngeal disorders causing vestibular signs, 1099, 1099f Horner’s syndrome as complication of surgery for, XIII:795-796 nasal, in dogs, 615-616, 625 (See under Polyps) nasopharyngeal, 625 of respiratory tract, XIII:794-796 (See also EVOLVE) Polyradiculoneuritis, 1115 Polysulfated glycosaminoglycans for hip dysplasia, 1122-1123 for osteoarthritis, XIII:1019-1020 Polytetrafluoroethylene paste, for urinary incontinence, 963 Polyurethane glue toxicity, 140 Polyuria and renal failure, XIII:849 definition of, XIII:14t polydipsia and, XIII:831-834, XIII:832t primary, XIII:832-833 urine collection to confirm, XIII:13t Polyuria and polydipsia (PU/PD), 844-850, 846t-847t Polyvinyl alcohol solutions, as tear substitutes, XIII:1064t Pomeranian(s), growth-hormone responsive dermatosis in, XIII:376 Poodle(s), growth-hormone responsive dermatosis in, XIII:376 Porphyria, XIII:416t Porphyromonas spp. vaccine, 1274 Portal hypertension after portosystemic shunt ligation, 586 from hepatobiliary disease, 546 Portography, 583, 585f, XIII:664-667, XIII:665f, XIII:666f Portosystemic shunt(s), 581-586 ammonium urate urolithiasis, in dogs with, XIII:872-874 clinical features of, XIII:682t congenital, XIII:668t, XIII:670 diagnosis and treatment of, 581-586 hepatic fibrosis and, XIII:679 hepatobiliary disease and, XIII:659 hepatoportal microvascular dysplasia and, XIII:682-686 (See also EVOLVE) polyuria and polydipsia from, 846t postoperative care with, 585-586, 585f radiographic diagnosis of, XIII:664-667 Portosystemic vascular anomalies, XIII:664-667, XIII:682t

  Index Positive end-expiratory pressure, 601 Positive pressure ventilation, for noncardiogenic pulmonary edema, XIII:811 Postobstructive diuresis, polyuria and polydipsia in, 846t Postpartum disorders, in the dog, 999-1002 Postrenal azotemia, 855 Potassium. See also Hyperkalemia; Hypokalemia administration of, intravenous, XIII:986t concentration of, in colloid fluids, 63t determining fractional excretion of, 1137 dietary recommendations for, in heart disease, 706-707 high, in erythrocytes, XIII:417t in abdominal fluid, 71 supplementation of for hypokalemic myelopathy, in cats, XIII:985-987 with ACE inhibitor therapy, XIII:712 with gastric dilatation-volvulus, XIII:166 supplementation of, in fluid therapy, 50t, 1137t with diabetic ketoacidosis, 217b, 218 with gastric dilatation-volvulus, 79 with hepatic lipidosis, 573 ventricular dysrhythmias and, XIII:153 Potassium bromide drug monitoring of, XIII:28t effect of, on thyroid function, 187t for seizures from intracranial tumors, 1079t, 1082 from traumatic brain injuries, 35t in dogs, XIII:960-962, XIII:961t with status epilepticus, 1063f, 1064 loading dose of, 1063f, 1064 Potassium chloride, supplementation of, for treatment of hypercalcemia, XIII:347 Potassium citrate, 935, XIII:889t Potassium gluconate, for hypokalemic cats, 1137 Potassium penicillin G, for prophylactic musculoskeletal problems, 1226t, 1228 Pralidoxime chloride (2-PAM) for cholinesterase inhibitor toxicity, 114t, 115, 121 for toxicity, XIII:207t, XIII:209-210 Pramoxine hydrochloride, topical use of, 411, 411t Praziquantel adverse reactions of, XIII:240t, XIII:241t for liver flukes, 580 for Paragonimus kellicotti, 671 Prazosin (Minipress) for feline lower urinary tract disease, XIII:889t, XIII:891 for hypertension, 912t, 913, XIII:840 for urinary retention, 955, 956t Precose, XIII:351, XIII:351t Prednisolone. See also Glucocorticoid(s) as immunosuppressive agent, 255, XIII:510 causing gastric ulceration, 498-499 comparison of, to other glucocorticoids, 401t definition of, 401-402 for anterior uveitis, 1205, 1206t for canine lymphoma, 336, 337t for chronic colitis, 519, 519t for episcleritis, in dogs, 1191t, 1192 for feline chronic bronchitis or asthma, 654 for feline gastrointestinal lymphoma, 341-342, 342t for feline idiopathic cystitis, 948 for feline infectious peritonitis, 1296b for feline lower urinary tract disease, XIII:889t for feline pruritus, 407-408 for hypercalcemia, XIII:347 for inflammatory bowel disease, 503, 505 for neurologic and musculoskeletal pain, 1128t for spinal cord disease, XIII:188 for tracheal collapse, 634 for vaginitis, 1011 ocular, 1150, 1150t use of, with infectious diseases, 1232-1233, 1233t

1377

Prednisone. See also Glucocorticoid(s); Prednisolone comparison of to cortisol, 401f to other glucocorticoids, 401t definition of, 401 effect of, on ACTH stimulation test, XIII:321 for feline stomatitis, 478 for hepatic fibrosis, XIII:680t for neurologic and musculoskeletal pain, 1128t ocular, 1150, 1150t use of, with infectious diseases, 1232-1233, 1232t, 1233t Pregnancy canine breeding management for, 974-979, 975f, 975t diagnosis of, XIII:918-923 with serum relaxin, XIII:924-929 endocrine biology of, XIII:947-948 false, 990-991 loss of, 987-989, 988b, 1234 termination of, XIII:947-954, XIII:951t, XIII:953f therapeutic recommendations for, XIII:931-933 dystocia, 992-998 feline diagnosis of, 1041 loss of, 1041-1046, 1042b, 1044b hormones, XIII:921-922 nutrition recommendations during, 1003-1007, 1004f progesterone for timing of ovulation and, XIII:914-915 termination of, 1031-1033 vaccine recommendation with, XIII:255 Premarin, for urinary incontinence, 957t, 958 Prerenal azotemia, 855 Prescription diets, for diabetes mellitus management, 205t Presyncope, 709 Primary ciliary dyskinesia, XIII:449t Primidone adverse effects of, crystalluria and uroliths as, XIII:847 associated liver disease, 568t drug monitoring of, XIII:28t in cats, XIII:965 toxicity of, XIII:217 Primucell, 1297, 1303, 1303b Probes, and DNA, XIII:246 Probiotic supplements, for flatulence, 526 Procainamide drug monitoring of, XIII:28t for supraventricular tachyarrhythmias, 726, XIII:729 for ventricular arrhythmias, 729, 738, XIII:735 with gastric dilatation-volvulus, 79, XIII:166 with heart failure, 778 in cats, XIII:101 ProcalAmine B, 20 Procarbazine, as chemotherapy, 309 Procaterol, toxicity from, XIII:154 Proestrus, in dogs, 975, 976f Progesterone concentration of during false pregnancy, 990 during normal gestation, 992 for ovulation timing in bitch, XIII:914-915 in the breeding cycle, 976f, 977, 978f with dystocia, in dogs, XIII:935 with feline ovarian remnant syndrome, 1040 with infertility, XIII:928 deficiency of, causing pregnancy loss in queens, 1043 effects of, on reproductive tract, 977 for estrus suppression, 1025 role of in hyperadrenocorticism, 221-223, 222t in pregnancy loss, 989t supplementation, 988-989, 989t toxicity of, 147-149, 148t-149t

1378

  Index

Progestin(s) adverse effects of, 1026 for estrus suppression, 1024-1028 Progestogen(s) for false pregnancy, 991 for feline pruritus, XIII:544 for intermittent erection in male castrated dogs, 1053 Prognosis, effect of lactate on, XIII:114-115 Progressive retinal atrophy autosomal recessive inheritance of, XIII:910t causing blindness, 1166 genetic test for, 1056t, 1057t Proguanil hydrochloride, 1290 Prolactin acepromazine for secretion of, 1001 concentrations of, during false pregnancy, 990 Proligestone adverse effects of, 1028 for estrus suppression, 1024-1025, 1027-1028 Propafenone (Rhythmol), for supraventricular tachyarrhythmias, 726 Propane toxicity, 134 Propantheline for feline lower urinary tract disease, XIII:889t, XIII:891, XIII:900-901, XIII:900t for syncope, 712t Proparacaine, for pain management, 15 Propionibacterium acnes, Propionibacterium acnes (Immunoregulin) for feline immunodeficiency virus, XIII:287 for feline leukemia virus, XIII:283 for feline retrovirus, 1281t, 1282 Propofol, XIII:123, XIII:125t constant-rate infusion (CRI) of, 89 for status epilepticus, 1063f, 1064 toxicity, 575 Propranolol (Inderal) effect of, on thyroid function, 187t for beta-agonist toxicity, XIII:155 for feline myocardial diseases, XIII:764 for feline ventricular tachyarrhythmias, 738 for hyperthyroidism, 176t, 178-179, XIII:335t Proptosis diagnosis and treatment of, XIII:1094 traumatic, XIII:1089 Propylene glycol toxicosis, XIII:226 diagnosis and treatment of, 132-133 from paintballs, 141-142 Propylthiouracil for hyperthyroidism, 176t, 178, XIII:334 use of, XIII:334t Prostaglandin(s) derivatives, for glaucoma, 1211, XIII:1079 for canine pregnancy termination, 1031-1032, XIII:950-951, XIII:951t, XIII:952 for metritis, 1000, 1000t for pyometra, 1009 Prostanoids, for pulmonary hypertension, 701 Prostatic cyst, with benign prostatic hypertrophy, 1047 Prostatic fluid, ejaculation of, XIII:916 Prostatic hypertrophy, benign, 1047-1048 Prostatitis, 1047-1048 Prostep ingestion, 136 Protease inhibitors, 537, XIII:699 Protein metabolism, hepatic dysfunction and, XIII:694-695 Protein(s). See also Hypoproteinemia; Proteinuria dietary, XIII:654 and renal failure, XIII:861 during illness, XIII:73-74 for diabetes mellitus management, 205t, 206 novel, 395-397 nutritional requirements for, 21b recommendations in heart disease, 706 levels of, in noncardiogenic pulmonary edema, 664 relationship to colloid osmometry, XIII:116

Protein-losing enteropathy diagnosis and treatment of, 512-515, XIII:641-643 nutritional support of, XIII:655-657 Protein-losing nephropathy, dietary recommendations for, XIII:846 Proteinuria control of, with chronic kidney disease, 874t, 877-878, 884-885, 887f, 889t diagnosis and treatment of, 860-863, 884f dipstick examination for, 887f from glomerular disease, 863-868, XIII:851 Proteus spp. causing urinary tract infections, 919, 920t, 922 minimum inhibitory concentrations (MIC) for, XIII:35t, XIII:42t role of, in struvite urolith formation, 851 urinary tract infection with, XIII:884 Prothrombin time (PT) in disseminated intravascular coagulation, XIII:192 in rodenticide toxicosis, 117-118 monitoring of, for warfarin therapy, 696 Prothrombin, role of, in disseminated intravascular coagulation, 288f, 289f Proton pump inhibitor(s) for esophageal disease, 484 for gastric ulceration, 500 Protothecosis neutrophil dysfunction in, XIII:449t ocular signs of, XIII:279 Protozoal infection(s) causing myocarditis, 805t causing pregnancy loss, 987-988 effectiveness of disinfectants and antiseptics against, XIII:259t neonatal diarrhea from, XIII:627t tritrichomonas, 509-512 Provera, 1028 Pruritus. See also Dermatitis; Skin allergen-specific immunotherapy for, 415-420 anal sac disease and, 466 atopy and, XIII:560-564 effect of diet on, 395-397 feline essential fatty acids for, XIII:541 therapy of, 405-410, XIII:542-545 from cyclosporine, 387-388 from drug hypersensitivity, XIII:556-559, XIII:557t hot spots and, XIII:549-551 shampoo therapy for, 410-412, 411t Pseudochylous effusion, 679 Pseudocyesis, 990-991 Pseudoephedrine for canine retrograde ejaculation, 1050-1051 for urinary incontinence, 957t, 958 toxicosis, XIII:153-157, XIII:156 Pseudohermaphroditism, 1036t, 1037-1039, XIII:905t, XIII:906 Pseudomonas infection bacterial resistance of, XIII:264 infective endocarditis from, 788t, 789 minimum inhibitory concentrations (MIC) for, XIII:35t, XIII:42t otitis externa from, 429, 435, 435t ear flushing for, XIII:584 flushing techniques for, 437-438 therapy of, XIII:585, XIII:587t treatment of, XIII:264 urinary tract infection from, 919, 920t, 1226-1227, XIII:884 Psychogenic polydipsia, 848 Psychotropic drugs, in feline pruritus, XIII:543-544 Psyllium (Metamucil), for constipation, in cats, XIII:651t Public health issues, and lead toxicity, 130 Puerperal tetany, 1001-1002 prevention of, 1004-1005 Pug encephalitis, 1071, 1073 Pulmonary artery catheter, hemodynamic monitoring with, 3-4

Pulmonary balloon valvuloplasty, 755-756 Pulmonary bullae, causing pneumothorax, 688-689, 688f Pulmonary contusions, 86-87 Pulmonary disease interstitial, 672-674, 673b respiratory acidosis and, 58b Pulmonary edema emergency treatment of, in cats, XIII:764 fulminant, sodium nitroprusside for, XIII:196 in heart failure, treatment of, 776 noncardiogenic, 663-665, XIII:810-812 reexpansion, 680-681 Pulmonary fibrosis, 672-674, 673b Pulmonary hypertension. See also under ­Hypertension causing syncope, 710b, 711t clinical classification of, 698b diagnosis and treatment of, 697-702, 699f-701f with patent ductus arteriosus, 744 with valvular heart disease, 781, 785 with ventricular septal defect, 750 Pulmonary infiltration with eosinophilia, 672-674, 673b Pulmonary neoplasia diagnosis and treatment of, 354-357, 355f with osteosarcoma, 362 Pulmonary outflow velocity, 701f Pulmonary parenchymal disease, in shock, XIII:144 Pulmonary system. See under Lung; Respiratory Pulmonary thromboembolism diagnosis and treatment of, 689-697 immune-mediated hemolytic anemia and, 268, 271, XIII:433 Pulmonary toilet, 608 Pulmonic stenosis causing syncope, 710b, 711t classification of disease severity, 755 clinical findings with, in cats, XIII:739t diagnosis and treatment of, 752-756 surgery for, XIII:745-746 therapy of, in cats, XIII:740t Pulse oximetry to determine oxygen effectiveness, 600 to determine oxygen needs, 597 Pulsus paradoxus, from pericardial effusion, 825 Punctum, nasolacrimal imperforate, XIII:1055 obstructed, XIII:1055-1056 Pupil. See also Anisocoria anatomy of, XIII:1045-1046 Pupillary escape, 1170 Pupillary light reflex anatomy of the, 1168-1170, 1168f, 1169f evaluation of, XIII:1038 normal, XIII:1045-1046 pathways for, XIII:1046f, XIII:1048f with anisocoria, 1172-1174, 1172t Puppy. See under Neonatal medicine; Orphan(s) Puppy strangles causing eyelid lesions, 1183-1184 use of glucocorticoids with, 1231 Purina veterinary diets DM, 208t Purpura, from drug therapy, XIII:557t, XIII:558-559 Putty compounds, 127 Pyelonephritis causing azotemia, 856b, 857 nephrotomy and, XIII:867 polyuria and polydipsia from, 846t, 848 Pyoderma. See also under Dermatitis; Dermatosis associated with hypothyroidism, XIII:328 effect of, on anal gland function, 466 empiric antimicrobial therapy for, 1226t, 1227 feline, treatment of, 406 methicillin-resistant canine, 449-450 neutrophil dysfunction in, XIII:449t shampoo therapy for, 413-414 urinary tract infection with, XIII:885 use of interferons for, 389-390

Pyogranuloma from hepatozoonosis, XIII:311 sterile, of eyelids, XIII:1052 Pyogranulomatous colitis, XIII:645 Pyometra diagnosis and treatment of, 1008-1009 in cats, XIII:930 causing pregnancy loss, 1043, 1043f incidence of, with estrogen therapy, 147-148 polyuria and polydipsia from, 846t Pyothorax, 676-678, XIII:820-821 Pyotraumatic dermatitis (hot spots), XIII:549-551 causes of, 447b, XIII:549t diagnosis and treatment of, 446-449 Pyrantel, adverse reactions of, in dogs, XIII:240t Pyrethrin-based insecticide(s) diagnosis and treatment of, 120b, 121-122 exposure to, 93-94, 97t Pyrethroid-based insecticide(s). See Pyrethrinbased insecticide(s) Pyridostigmine bromide (Mestinon) adverse effects of, 1109 for autoimmune myasthenia gravis, 1109-1110 for myasthenia gravis, 490 Pyridoxine shampoos, 412t, 413 Pyriproxifen for house dust mite control, 427 toxicity of, 123-124 Pyruvate kinase deficiency, XIII:416t, XIII:419 autosomal recessive inheritance of, XIII:910t genetic test for, 1057t Pythiosis, diagnosis and treatment of, 1268-1271 Pythium spp., in dogs, XIII:313-315 Pyuria, 918 Q Quarantine with canine influenza, 1293-1294 with feline coronavirus, 1298 with feline viral diseases, 1301 Quaternary ammonium compounds, as disinfectant, XIII:259 Quinapril, for heart failure, 772-774 Quinidine gluconate, to facilitate cardioversion, 740-741 Quinidine sulfate drug monitoring of, XIII:28t for ventricular arrhythmias, XIII:735 Quinolone(s). See Fluoroquinolone(s) Quintox toxicity, XIII:215-216 R Rabies, XIII:294-295. See also EVOLVE postexposure prophylaxis recommendations for, XIII:294-295 vaccination fibrosarcoma from, XIII:498 recommendations for, 1272, 1273t, 1275, 1276t, XIII:250 Radiation therapy basic principles and indications for, 315-319 for acral lick dermatitis, 471, XIII:554 for anal sac tumors, 383 for bladder cancer, 371 for canine lymphoma, 337 for hemangiosarcoma, 330 for hyperadrenocorticism, 226-227 for intracranial tumors, 1080-1081, 1080t for mammary cancer, 365 for mast cell tumors, 376 for melanoma, 380 for nasal tumors, 352-353, 615 for osteosarcoma, 361-362 for soft-tissue sarcomas, 326 nasopharyngeal tumors, 626 of pituitary tumors, XIII:367-368 radioiodine, 180-184 safety precautions for, 183 sensitivity to, 316 side effects from, 318-319 systems of, XIII:482-485 use of, XIII:482-485 with chemotherapy and surgery, 317, 323-324

  Index Radioactive iodine therapy, XIII:484-485 for feline hyperthyroidism, 180-184 advantages and disadvantages of, 176t, 180-181 medical therapy and, XIII:337 use of methimazole before, 178 systems for, XIII:484-485 Radioallergosorbent assay (RAST), for food allergy, XIII:634 Radiography contrast medium, causing nephrotoxicity, 160b for evaluation of acute abdomen, XIII:162 adrenal mass, XIII:369-370 atlantoaxial subluxation, 1085, 1085f azotemia, 858 bacterial pneumonia, 660 cervical vertebral instability-malformation syndromes, XIII:994t chronic bronchitis and feline asthma, 650, 652-653 chronic bronchitis, in dogs, 642 dilated canine cardiomyopathy, 793 dystocia, in dogs, XIII:936 elbow joint disorders, XIII:1007-1009 feline heartworm disease, 834, 834f, XIII:785-786, XIII:785f feline lower urinary tract disease, 946t feline urinary calculi, 932-933, 937-938, 938f gastrointestinal motility, XIII:611-613 (See also EVOLVE) GDV, 77-78 heart failure, 777f hip laxity, 1122 interstitial lung diseases, 672-674 kidney masses, 925-927 lung worms, 668f mast cell tumors, 375 mitral valve dysplasia, 766-767 myocarditis, 805 noncardiogenic pulmonary edema, 663 osteosarcoma, 358 patent ductus arteriosus, 744, 745f pelvic trauma, XIII:1024-1025, XIII:1028-1029 pericardial effusion, 826, XIII:773 pneumothorax, 685 portosystemic anomalies, XIII:664-667 pregnancy, in dogs, XIII:920-921, XIII:922f pulmonary hypertension, 699 pulmonary thromboembolism, 691 pulmonic stenosis, 753 supraspinatus tendon disorders, 1118, 1118f thoracic trauma, 86-87 tracheal collapse, 632, 638f, XIII:798 tricuspid valve dysplasia, 763, 764f valvular heart disease, 782 ventricular septal defect, 748-749 of nasopharynx, 623 of the liver, 547 of the nose, 352, 610, 614 Radiology interventional, in urinary diseases, 965-971 Radiotherapy. See Radiation therapy Raison toxicity. See Grape and raison toxicity Ramipril for dilated cardiomyopathy, in dogs, 794-795, 794t for feline cardiomyopathy, 811t, 813 for heart failure, 772-774 Rampage toxicity, XIII:215-216 Randomization, 298 Ranitidine (Zantac) for gastric ulceration, 500 for gastrointestinal disorders, due to shock, XIII:144 for uremic gastropathy, 916 for vomiting cats, 574 toxicity of, XIII:229 use of, XIII:615t, XIII:616-617 during shock, 7 with kidney failure, XIII:865t

1379

Rapamycin (Rapamune), as immunosuppressive agent, 257 Rapid card agglutination test (RCAT), for brucella canis, 986 Rapid urease test, for Helicobacter spp., 494, 494f Rat poison. See Rodenticide toxicity Rate responsive pacing systems, 718t, 719-721 Rathke’s cleft, cystic, 626 Rathke’s pouch, XIII:376 Rauwolscine, for canine retrograde ejaculation, 1050 Raw meat diet, 166-167 Reactive fibrohistiocytic nodules, 464 Recombination fraction, 1055 Rectal disorders, diagnosis and treatment of, 527-531 Rectal prolapse, 530-531 Rectal strictures, 530 Rectal suppositories, XIII:650, XIII:651t Rectovaginal vestibular fistula, 1014 Recumbent patient, managing the, 1133 Red blood cell(s). See also under Hematology cytograms and histograms of in anemic dogs, XIII:382f in cats, XIII:383f in normal dogs, XIII:382f feline, disorders of, XIII:421-424 (See also EVOLVE) Red cell aplasia, 273-274 Red eye algorithm for, XIII:1042f differential diagnosis of, XIII:1042-1045 tonometry for, 1141-1142 Refeeding syndrome, XIII:87-89 Regurgitation from esophagitis, 483 from megaesophagus, 489 Rehabilitation, for neurologic patients, 1131-1135 Rehydration, fluid therapy and, 48-54 Relaxin, for pregnancy diagnosis, 986, XIII:922, XIII:924-929 Remifentanil, for pain management, 11, 11t, 12f-13f Renal cell carcinoma, 926-927, 927f Renal disease(s). See also Urinary tract infection; specific disease abnormalities suggestive of, 885b approach to azotemia from, 855-860 diagnosis of, 883, 884f, 885f effect of ACE inhibitors on, XIII:713 from ureteroliths, in cats, 931-935 from urolithiasis and ureteroliths, in cats, 931f, 932f gastrostomy tube feeding in, 906-910 glomerular, 863-868 hypertension and, 713, 714t, 910-913 measuring glomerular filtration in, 868-871, 871b neoplasia of, 925-930, 927f proteinuria with, 860-863 role of potassium in, 1138 treatment of, 872-879 urine collection, indications for timed, XIII:13t Renal failure acid-base disorders in, 60 acute, XIII:173t diagnosis and treatment of, 879-882, 880t diagnosis of, XIII:856-858 and treatment of, XIII:173-178 differential diagnosis for, XIII:213t from grape and raison toxicity, 142-143 from leptospirosis, 1237-1240, XIII:308-309 from lilies, 143 hemodialysis for, 896-900 nephrotoxins causing, 159-164, 161b, XIII:212-216, XIII:213t prevention of, and prognosis for, XIII:177-178 risk factors for, XIII:857t shock and, XIII:143 therapy of, XIII:849-850 acute vs. chronic, differentiation of, XIII:856-858, XIII:856t (See also EVOLVE)

1380

  Index

Renal failure (Continued ) anemia treatment with, 914-918 chronic, 883-892 anorexia from, XIII:864t, XIII:865 calcitriol therapy for, 893-895, XIII:862 diagnosis and treatment of, 883-892, 884f, 885b, 885f, 886f, 886t, 889t, 890t diagnosis of, XIII:856-858 dietary recommendations for, XIII:842t, XIII:843t, XIII:846 differential diagnosis for, XIII:213t from nephrotoxins, 159-164, 160b kidney transplant for, 901-906 peritoneal dialysis for, XIII:859-861 (See also EVOLVE) progressive, management of, XIII:861-864 proteinuria with, 860 stages of, 883-885, 886f treatment of, using evidence-based medicine, 873 urine collection for, XIII:13t with diabetes mellitus, 215 effect on thyroid function, 187 from glomerulonephritis, 863-867 gastrostomy tube feeding in, 906-910 hemodialysis for, 896-900 hypercalcemia and, 236-240, 239f, 240f, 249 hypertension from, 713, 910-913, 911f hyperthyroidism and, 177, 181-182 after radioiodine therapy, 183-184 measuring glomerular filtration in, 868-871, 871b polyuria and polydipsia in, 846t, 848 Renal medullary washout, polyuria and polydipsia from, 846t Renal neoplasia, 925-930, 927f Renal transplantation, 901-906, 935 centers for, 903b immunosuppressive agents for, 254-256 screening of transplant candidates, 901-903, 902f Renin-angiotensin-aldosterone system activation of, 704 effect of ACE inhibitors on, XIII:712-713 effect of diuretic therapy on, XIII:712 Renomegaly, 926, 926b Reproductive disorders associated with hypothyroidism, XIII:327 associated with obesity, 192b benign prostatic hypertrophy, 1046-1047 canine pregnancy termination, 1031-1033 differential diagnosis of, with acute abdomen, 68t dystocia, 992-998 estrus suppression, 1024-1030 false pregnancy, 990-991 genetic diseases causing, 1034-1040, 1035f intermittent erection in male castrated dogs, 1053 mastitis, 1001 metritis, 1000 ovarian remnant syndrome, in cats, 1040-1041 postpartum, 999-1002 pregnancy loss in the bitch, 987-989 in the queen, 1041-1046, 1044b prostatitis, 1047-1048 puerperal tetany, 1002 pyometra, 1008-1009 retrograde ejaculation in the dog, 1051f subinvolution of placental sites, 999 uterine prolapse, 999-1000 vaginal anomalies, 1012-1018 vaginitis, 1010-1011, 1011b Reproductive failure from hypothyroidism, 185 in cats, XIII:929-931 Reproductive physiology, in dogs, 974-979 Reproductive tract, inherited disorders of, XIII:904-909 Research, in clinical trials in oncology, 297-300, 298t Resolve spot and stain carpet cleaner, 110

Respiration pattern of, in cats, XIII:100t Respiratory acidosis, 55-58, 55t, 58b. See under Acidosis Respiratory alkalosis, 55-58, 55t, 57b. See under Alkalosis Respiratory disease(s) airway management for, XIII:790-794 (See also EVOLVE) asthma, in cats, 650-658 bacterial pneumonia, 658-662 Bordetella bronchiseptica bronchitis, 646-649 brachycephalic upper airway syndrome, 619621, 628-629 chronic bronchitis in cats, 650-658 in dogs, 642-645 from Calicivirus, in cats, 1284-1287 from canine heartworm disease, 838 from canine influenza, 1291-1294 from Chlamydia, in cats, 1185-1187 interstitial lung diseases, 672-674 laryngeal, 627-630 nasopharyngeal disorders, 622-626 noncardiogenic pulmonary edema, 663-665 oxygen therapy for, 596-603 parasites of, 666-671 pleural effusion, 675-684 pneumothorax, 685-689 polyps (See under Nasopharyngeal disorders) pulmonary hypertension, 697-702 pulmonary thromboembolism, 689-697 rhinitis causing, 609-618 tracheal collapse, 630-635 stenting for, 635-641, 637f, 638f, 639f, 640f tumors of the, XIII:500-504 ventilator therapy for, 603-609 with valvular heart disease, 785 Respiratory distress. See Cough; Pleural effusion Respiratory distress syndrome, in shock, treatment of, XIII:144 Respiratory failure definition of, 603 ventilator therapy for, 603-609 Respiratory infection(s) empiric antimicrobial therapy for, 1226t, 1227-1228 from Bordetella bronchiseptica, 646-649 fungal, XIII:815-819 rational use of glucocorticoids with, 1230-1231 with chronic bronchitis, 642-645 with tracheal collapse, 631f, 633 Respiratory parasites, 666-671 Respiratory tract, humidification of, XIII:790-791 Resting energy requirements (RER), 19, 207, 207t Resuscitation circulatory, in gastric dilatation-volvulus, 78-79 goals of, with colloid therapy, 65t Reticulocyte count(s) erythrocyte morphic patterns relating to, XIII:381 with anemia, in chronic kidney disease, 917 Retina, diseases of. See also Blindness; Eye; Ophthalmic anisocoria from, 1172-1173, XIII:1048t blindness from, 1165-1166 drug therapy for, 1148 mydriasis from, 1171 retinitis, associated with systemic infectious diseases, XIII:277t retinopathy, hypertensive, XIII:1082-1085 (See also EVOLVE) Retinal degeneration blindness from, 1166, XIII:1039 sudden acquired, XIII:1093 Retinal detachment blindness from, 1165-1166, XIII:1039 diagnosis and treatment of, 1215-1219, 1217f from hypertension, 713-716, 714t, 715b, XIII:840

Retinal hemorrhage differential diagnosis for, XIII:1084 from hypertension, 713, 714t Retinochoroiditis, causing retinal detachment, 1216 Retinoids, as chemotherapy, XIII:476 Retinopathy, canine multifocal, genetic test for, 1056t Retrobulbar injection, 1148 Retroillumination, of the eye, 1140, 1141f, 1171 Retropulsion of the globe, 1144 Retroviral infection, of the nervous system, XIII:288-291 Reverse sneezing, in dogs, 609, 622 Rhabdomyosarcoma, nasal and paranasal, XIII:501t Rhinitis in cats, 616-618 in dogs, 609-616, 610b, 611f, 612f Rhinoscopy in cats, 617 in dogs, 610-616 Rhinosinusitis, in cats, 616-618 Rhinotomy, 613, 624 Rhipicephalus sanguineus, as vectors, XIII:296-297 Rhodanine stain, of liver, 559b Ribavirin, for feline retrovirus, 1281t Rickettsial infection(s) causing myocarditis, 805t causing neonatal diarrhea, XIII:627t causing vestibular signs, 1100 Right ventricular cardiomyopathy, in cats, 815-818 Right-to-left shunting, with ventricular septal defect, 751 Rimonabant (Acompia), 195 Ringworm. See Dermatophytosis RNA, based diagnostic techniques, XIII:455-457 Rochalimaea infection. See Bartonellosis Rocky Mountain spotted fever conjunctivitis from, XIII:1054 ocular signs of, XIII:277 thrombocytopenia from, 282t, XIII:440, XIII:441t vector associated with, XIII:296t vestibular signs from, XIII:970 Rod cone dysplasia, genetic test for, 1057t Rodenticide toxicity, XIII:211-212 anticoagulant, XIII:211 treatment of, 113-114, 114t, XIII:208-209 calcium disrupting, XIII:215-216 causing nephrotoxicity, 160b, 162 diagnosis and treatment of, 117-119 exposure to, 93, 95-99, 97t Ronidazole, for tritrichomonas, 510 Roofing felt, 127 Rose bengal stain, 1144 Rotavirus, neonatal diarrhea from, XIII:627t Rotenone toxicity, 120b Rowasa, 519 Royal Canin diabetic DS 44, 208t Rubeanic acid stain, of liver, 559b Rumel tourniquet, for CPR, 29 Rutin, for chylothorax, 679 S S-adenosylmethionine (SAMe) for acetaminophen toxicity, 113, 114t for drug-associated liver disease, 569 for hepatic lipidosis, 573 for hepatic support, 555-556 Sacrococcygeal injuries, XIII:1023-1026 Sacroiliac dislocation, XIII:1026-1032 Sacrum, fractures of, XIII:1024f-1025f, XIII:1025-1026 Salicylate(s), toxicity of, 433b, 519 Salicylic acid shampoos, 412-413, 412t, 414, 414t Salmeterol toxicity, XIII:154, XIII:154t Salmon poisoning disease neonatal diarrhea from, XIII:627t thrombocytopenia from, 282t

Salmonella spp causing neonatal diarrhea, XIII:626, XIII:627t causing pregnancy loss, 987 in homemade pet foods, 166 thrombocytopenia from, 283t, XIII:440, XIII:441t Salviannolic acid B, for feline infectious peritonitis, 1297t SAM-e. See S-adenosylmethionine (SAMe) Samarium-EDTMP, 362 Samoyed(s) growth-hormone responsive dermatosis in, XIII:376 sebaceous adenitis in, XIII:572-573 Sandimmune. See Cyclosporine Sanguinaria canadensis, 151t Sarcoidosis, 464-465 Sarcoma(s). See also Neoplasia; Soft-tissue sarcoma optic, XIII:1096 post-traumatic in cats, XIII:1096 ocular, 1157 renal, 927 vaccine-associated, 332-335 Sarcoptic mange skin scraping for, XIII:526 treatment of, 392-393 Scattergrams, of erythrocytes, XIII:381-383. See also EVOLVE Schiøtz tonometry, XIII:1076 Schirmer tear test, 1143-1144, XIII:1061-1062. See also EVOLVE Schistocytosis, in disseminated intravascular coagulation, XIII:191-192 Schwartz’s dictum, 500 Scintigraphy for assessment of gastrointestinal motility, XIII:613 for esophageal evaluation, 489 for feline urinary calculi, 933 for gastrinoma, XIII:619f for hepatoportal microvascular dysplasia, XIII:684 for liver evaluation, 548 for portosystemic shunts, 583, 585f for pulmonary thromboembolism, 692 Scleritis, in dogs, 1192 Scottish terriers, benign prostatic hypertrophy in, 1046 Scraping, technique for cytology, 302 Sebaceous adenitis, therapy for, 451-453, XIII:572-573 Seborrhea essential fatty acids for, XIII:541 shampoo therapy for, 412-413, 412t Sedation for mechanical ventilator support, 607-608 for relief of feline urethral obstruction, 953 Seizure(s). See also Epilepsy after portosystemic shunt surgery, 585-586 feline, XIII:963-966, XIII:964t hypocalcemia causing, 242, 244 hypoglycemia causing, XIII:358-359 hypothyroidism causing, XIII:974 lawn care products causing, XIII:222 management of, in dogs, XIII:959-963 new anticonvulsant drug therapy for, 1066-1069 treatment of status epilepticus, 1062-1065, 1063f vs. syncope, 709 with intracranial tumors, 1082 Selamectin (Revolution) for cheyletiellosis, 393 for ear mites, 393, 436 for feline heartworm prevention, 835, 835t for fleas, 394 for nasal parasites, 624, 666-667 for sarcoptic mange, 393 toxicity of, 125-127 use of, in dermatology, 391-392 Seldinger technique, 39 Selegiline. See L-Deprenyl Selenium disulfide shampoos, 412t, 413

  Index Selenium sulfide shampoos, 414 Selenium, for pancreatitis, XIII:699 Self-mutilation. See Sensory mutilation Semen. See also Sperm effect of hypothyroidism on, in male dog, XIII:940-941 for artificial insemination collection of, XIII:916 fresh vs. frozen, XIII:916 fresh or chilled, 985 frozen, 984-985 Seminoma, XIII:943 Sensitivity and specificity. See Culture(s) Sensory mutilation, XIII:90-93 Sepsis. See also Bacteremia; Shock associated with disseminated intravascular coagulation, 287-291, 289b associated with drug induced liver disease, 569 bacterial translocation and, XIII:201-203 (See also EVOLVE) causing polyuria, XIII:832 causing shock, 2 cholestasis of, XIII:669 diagnosis of, XIII:273t effect on thyroid function, 187 empiric antimicrobial therapy for, 1226t, 1229 ocular manifestations of, XIII:276 risk for pulmonary thromboembolism, 696 therapy of, XIII:271-275, XIII:274t thrombocytopenia from, XIII:440 use of glucocorticoids with, 1231-1232 SEPTI-serum, for bacterial translocation, XIII:202 Septic abdomen diagnosis of, 71, 74b drainage techniques for, 72-76, 74f Septic arthritis, empiric antimicrobial therapy for, 1226t, 1228-1229 Septic mastitis, 1001, 1001f Septic metritis, 1000 Serology, for herpesvirus-1, in cats, XIII:1058 Serotonin reuptake inhibitors for acral lick dermatitis, 472-473 for feline pruritus, XIII:543-544 Serotonin syndrome toxicity, 114t, 115 Serratia marcescens, for feline retrovirus, 1281t Serratia spp., minimum inhibitory concentrations (MIC) for, XIII:35t, XIII:42t Sertoli cell tumor, XIII:943 Sevelamer hydrochloride (Renagel), 894 Severe combined immunodeficiency, XIII:516-517 Sex reversal, 1035-1036 Sexual development disorders of, XIII:904-905, XIII:905t normal, 1034, 1035f, XIII:904, XIII:904f Shaking pup syndrome, X-linked inheritance of, XIII:910t Shampoo therapy, 410-415, 411t, 412t, 414t antifungal, 459t for pyotraumatic dermatitis, 447, XIII:550-551 Shampoo toxicity, XIII:223-224 Shar-pei dog(s) amyloidosis in, 866 immunodeficiency syndrome of, XIII:517 Shearing wounds, XIII:1032-1035 Shelter-housed pets control of canine influenza in, 1293-1294 control of feline coronavirus, 1298 vaccination guidelines for cats, 1277 vaccination guidelines for dogs, 1274 Shetland sheepdog(s) avermectin toxicosis in, 125-127 von Willebrand’s disease in, XIII:434 Shiøtz tonometer, 1142 Shock adrenal insufficiency causing, 228-229 associated with drug induced liver disease, 569 cardiogenic, 769, 776-777 classifications of, 3b colloid use in, XIII:133t, XIII:134-135

1381

Shock (Continued ) diagnosis and treatment of, 2-8, XIII: 140-147 effect of, on liver, XIII:668t fluid therapy for, 48-54 management of, in cats, XIII:99 use of oxygen therapy for, 596-603, 597b Shunt causing hypoxemia, 604 portosystemic. See (Portosystemic shunt) Siamese cat, prevalence of asthma in, 652 Sibutramine (Meridia), 194 Sick euthyroid syndrome, 187 Sick sinus syndrome, XIII:721, XIII:721f causing syncope, 710, 710b, 711t, 712t permanent cardiac pacing for, 717-721 Silastic implants, 1028 Sildenafil (Viagra) for heart failure, 774, 779t for pulmonary hypertension, 701, 750 Silica gel packet ingestion, 93 Silica urolithiasis breeds at risk for, 857t compound with, XIII:876 Silver sulfadiazine, otic, 431t Silybin-phosphatidylcholine (Marin), 555, 579 Silymarin (milk thistle) for hepatic support, 555 for portosystemic shunt, 585f, 586 Simethicone, for flatulence, 526 Single-lead atrial synchronous pacing, 720-721, 720f Sinoatrial node disorders, causing bradyarrhythmias, XIII:721 Sinus arrest, transvenous pacing for, XIII:198 Sinus arrhythmia, XIII:721f Sinus bradycardia, in cats, 734 Sinus disorders, causing nasal discharge, 610b Sinus tachycardia in cats, 735, 736f in gastric dilatation-volvulus, 79, 81 Sirolimus, as immunosuppressive agent, 257, XIII:512-513 Skin. See under Dermatologic disorder(s); ­specific disorder histiocytic diseases of, XIII:588-591 papilloma viruses of, XIII:569-570 pythiosis of, XIII:313-315 scraping, XIII:526-527 for feline demodicosis, 440 ulcerations of and renal glomerulopathy of Greyhound dogs, XIII:854-855 (See also EVOLVE) differential diagnosis for, XIII:855 Skin cancer. See Squamous cell carcinoma Skin tumors radiation therapy for, XIII:482-485 round cell, immunophenotyping for, XIII:506-508 Skye terrier, inherited copper hepatitis, 561 Slide preparation fixation and staining, 303-304 for cytology, 302-303, 303f Slit-lamp biomicroscopes, 1140 Small intestinal bacterial overgrowth, XIII:637-641 (See also EVOLVE) transit, XIII:612, XIII:612t Smear preparation, 303-304, 303f Smoking cessation products, 136t Snake venom causing nephrotoxicity, 160b, 856b vaccination for, 1274 Sneeze barriers, 1300 Sneezing in cats, 616-618 in dogs, 609-616 Snuff toxicity, 136t Soap, toxicity of, XIII:223-224 Sodium. See also Hypernatremia; Hyponatremia concentration of, in colloid fluids, 63t dietary, and refractory heart failure, XIII:754 restriction of, with heart disease, 704-708, 784, 793, 796, XIII:713-714

1382

  Index

Sodium bicarbonate. See also Bicarbonate for hyperkalemia, 952 for metabolic acidosis, 234, 952 use of, in CPR, 32 Sodium bromide, for status epilepticus, 1063f, 1064 Sodium fluoride, causing nephrotoxicity, 160b Sodium hypochlorite (Bleach) as disinfectant, XIII:260 toxicity of, XIII:224-225 Sodium nitroprusside. See Nitroprusside Sodium stibogluconate, for leishmaniasis, 1253 Sodium urate crystalluria, 851t Soft palate abnormalities, 619-621 Soft tissue tumors, radiation systems for, XIII:482-485 Soft-tissue sarcomas canine, diagnosis and treatment of, 324-328 radiotherapy for, 318 Solanum spp., 151t Solders, 127 Solvent(s) toxicity, 134-135 Somatostatin, for chylothorax, 679-680 Somogyi phenomenon, 203, 210-211 Sotalol for supraventricular tachyarrhythmias, 726 for syncope, 712t for ventricular arrhythmias, 729, 796, XIII:736-737 in boxers, 799 in cats, 738, 818 with heart failure, 775 Southern analysis, of DNA, XIII:246 Southernwood essential oil, 152t Specimen collection, for cytology, 301-304 Sperm count, and relationship to testes size, XIII:942t disorders from retrograde ejaculation in the dog, 1049-1052 for transcervical canine insemination, 983-985 frozen, chilled and fresh, 984-985 granuloma, XIII:945 survival, in dogs, 974, 975t Spherocytosis, autoimmune hemolytic anemia and, 267, XIII:429 Spinal cord disease. See also Intervertebral disc disease medical management of, acute, XIII:186-189 Spinal pain management, 1126-1131 Spinal reflexes, occurring with ejaculation, 1050, 1052 Spironolactone for ascites from liver disease, 556 for dilated cardiomyopathy, in dogs, 793-794, 796 for Doberman pinscher cardiomyopathy, 802 for feline cardiomyopathy, 811-814, 811t, 818 for heart failure, 772-774, 779t, 784 for outpatient heart failure, XIII:750 for refractory heart failure, XIII:755 for syncope, 712t for systemic hypertension, 716 with renal disease, 912t for ventricular septal defect, 750 Spleen diseases of, XIII:520-524 functions of, XIII:520-521 neoplasia of, XIII:521-522 splenomegaly, causes of, 521t, XIII:521-522 torsion of, XIII:521t Splenoportography, for portosystemic anomalies, XIII:664 Splinting, for atlantoaxial subluxation, 10851086, 1086f Spondylomyelopathy, canine cervical, 10881093 Spontaneous pneumothorax, 687-689, 688f Squamous cell carcinoma eyelid, 1155-1156, 1155f, 1183 in situ (Bowen’s disease), 424 nasal and paranasal, XIII:501t of lung, XIII:504t

Squamous cell carcinoma (Continued ) of nasal plane, XIII:500-501, XIII:500t of the larynx and trachea, XIII:503t papillomatosis and, 445 Sry gene, 1036 Stable iodine, XIII:334t, XIII:335t Standard poodle(s) sebaceous adenitis in, XIII:572-573 von Willebrand’s disease in, XIII:434 Stanozolol, associated liver disease, 568t, 575 Staphylococcal protein A (SPA) for feline leukemia virus, XIII:283 for feline retrovirus, 1281-1282, 1281t Staphylococcus spp. infection causing blepharitis, 1178-1179 causing otitis, 435 causing pyoderma, 1227 causing urinary tract infections, 919, 920t, 1226, XIII:884 methicillin-resistant canine, 449-450 minimum inhibitory concentrations (MIC) for, XIII:35t, XIII:42t resistance of, XIII:265-266 role of in acral lick dermatitis, XIII:552 in hot spots, 447, XIII:549 in infective endocarditis, 787-788, 788t in struvite urolith formation, 851 treatment of, XIII:266 Staphyloma, 1162, 1162f Starling-Landis equation, 61, 62f Starvation. See Anorexia; Nutrition Status epilepticus, 1062-1065, 1063f Stavudine, for feline retrovirus, 1281t Steimann pins, for cervical vertebral instabilitymalformation syndromes, XIII:997-998 Stem cell factor (SCF), XIII:406-407 Stenosis, nasopharyngeal, 625-626 Stenotic nares, 619-620 Stent for occlusion of portosystemic shunt, 584-585 for tracheal collapse, 634, 635-641, 637f Stereotactic radiosurgery, for osteosarcoma, 362 Steroid implants, 1028 Steroid myopathy, 1114 Steroid-responsive meningitis-arteritis, 1073, XIII:978-981 Steroids. See Glucocorticoid(s) Stilbestrol, for urinary incontinence, 956, 957t Sting. See Bite(s) Stomatitis feline, 476-478, XIII:600-602 immunodeficiency virus-associated, XIII:286 from uremia, XIII:864 Stomatocytosis, XIII:417t Stratification, 298, 299f Streptococcus pneumoniae, resistance of, XIII:262 Streptococcus spp. causing urinary tract infections, 919, 920t, 1226, XIII:884 role of, in infective endocarditis, 787-788, 788t Streptokinase, for thrombolysis, 695 Streptozotocin (Zanosar), for insulinoma, XIII:360 Stress adrenal insufficiency during, 228-230, 235 and acral lick dermatitis, 469 management for feline idiopathic cystitis, 949-950, XIII:895 related mucosal disease (SRMD), shock and, 7 role in feline coronavirus, 1298 Stroke. See Cerebrovascular accident Stromal dystrophy, XIII:1068 Stromal keratitis, 1162 Stromal puncture needles, 1198-1199 Strong ion difference, 59-60, 60b in acidosis and alkalosis, 59-60, 59b, 59t Strong ion gap, 55-56, 56b, 59-60 Strong ions disorders. See Acid-base balance; Acidosis; Alkalosis Strontium 90, XIII:484

Struvite crystalluria, 851, 851t, 853, 853f Struvite urolithiasis breeds at risk for, 857t compound with, XIII:874-875 dietary recommendations for, XIII:846 in cats, XIII:843t in dogs, XIII:846t Strychnine toxicosis, 118, XIII:211-212 Subaortic stenosis cardiac catheterization for, XIII:742-744 clinical findings with, in cats, XIII:739t diagnosis and treatment of, 757-761, 758f prophylactic antibiotics with, 791 surgery for, XIII:746 therapy of, in cats, XIII:740t Subconjunctival injection, 1146, 1151 drug dosages for, 1147t for anterior uveitis, 1206, 1206t immunotherapy, 1149-1151, 1150t Subcutaneous fluid therapy, 152 Subvalvular aortic stenosis. See Subaortic stenosis Succimer, for lead toxicity, 129 Sucralfate (Carafate) for chronic kidney disease, 873t, 877, 916 for esophageal disease, 485, XIII:609 for gastric ulceration, 500 for ulcerations, due to shock, XIII:144 use of, in shock, 7 with kidney failure, XIII:865, XIII:865t Sudden death, in Doberman pinschers, 802 Suicide right ventricle, 755 Sulfadiazine, adverse effects of, XIII:240t, XIII:847 Sulfadimethoxine, adverse effects of, XIII:240t Sulfapyridine, 518 Sulfasalazine for colitis, 518-519, 519t, XIII:646-647 for inflammatory bowel disease, 505 Sulfonamides causing crystalluria, 851t, XIII:847 causing liver disease, 568t causing nephrotoxicity, 160b Sulfonylurea. See also Glipizide adverse effects of, XIII:352 for non-insulin dependent diabetes mellitus, XIII:351-352 (See also EVOLVE) Sulfosalicylic acid (SSA) turbidimetric test, 860 Sulfur metabolite, compound uroliths with, XIII:876t Sulfur shampoos, 412-413, 412t Sulindac, toxicity of, 162, XIII:227 Sulindae, toxicity of, XIII:214-215 Sunflower oil, as essential fatty acid, XIII:538-539 Superglue ingestion, 140 Superinfections, 923-924 Supraspinatus tendon disorders, in dogs, 1117-1120, 1118f Supraventricular premature complexes, in cats, 736 Supraventricular tachyarrhythmias (SVT), 722-727, 724f, 725f, 725t in cats, 736-737, 736f with dilated cardiomyopathy, in dogs, 795 Supraventricular tachycardia. See Arrhythmia, supraventricular Suprelorin, 1029 Suprofen for anterior uveitis, 1205, 1206t for ocular diseases, 1151t, 1152 Suramin, for feline retrovirus, 1281t, 1282 Surgery alternatives to exploratory celiotomy and, XIII:17-21 cardiac, indications for, XIII:745-748 (See also EVOLVE) early age neutering, 1019-1024 for adrenal gland disease, XIII:371 for anal sac tumors, 383 for atlantoaxial subluxation, 1086-1087, 1086f for bladder cancer, 371 for brachycephalic upper airway syndrome, 619-621, 629

Surgery (Continued ) for canine cervical spondylomyelopathy, 1089-1093 for cervical vertebral instability-­malformation syndromes, XIII:996-1000, XIII:996t for chylothorax, 680-681 for degenerative lymphosacral stenosis, 1095 for feline glaucoma, 1212 for feline ovarian remnant syndrome, 1040-1041 for feline vaccine-associated sarcoma, 333 for gastric dilatation-volvulus, XIII:167-169 for glaucoma, XIII:1079-1081 for hemangiosarcoma, 330 for insulinoma, XIII:359-360 for intracranial tumors, 1078, 1080t for keratoconjunctivitis sicca, XIII:1065-1066 for laryngeal paralysis, 628 for lung lobe torsion, 683-684 for mammary cancer, 365, 368 for nasopharyngeal disorders, 623-624 for nonhealing corneal ulcers, 1198-1199 for open fractures, XIII:171-172 for osteosarcoma, 360-361 for patent ductus arteriosus, 746-747 for pneumothorax, 688-689 for primary hyperparathyroidism, 250-251 for pyothorax, 677-678 for renal tumors, 927-930 for soft-tissue sarcoma, 326 for splenic disorders, XIII:523 for supraspinatus tendon disorders, 1119 for syringomyelia and Chiari-like malformation, 1104-1106, 1105f for tracheal collapse, 634-635, XIII:800 interluminal stenting, 635-641, 637f for traumatic brain injury, 37 for ureteral calculi removal, 933-935 for vaginal anomalies, 1012-1018 for valvular heart disease, 785 for ventricular septal defect, 750-751 kidney transplant, 901-906, 935 nephrectomy, 935 pain management for, XIII:57-61 pericardectomy, 680, 829-830 preparation for, to minimize risk of infection, XIII:261 principles in oncology, 320-324 prophylactic antimicrobial therapy for musculoskeletal, 1226t, 1228 Surgical debridement, with open factures, 84-85 Surgical site infections, methods for reducing hospital acquired, 1224 Surveillance, for hospital-acquired infections, 1223 Swallowing process, 479-480, 487. See also Dysphagia Swan-Ganz.. See catheter(s), Swan-Ganz Sweetener toxicity, 139-140 Swiffer WetJets toxicity, 109 Sympathetic nerves, anisocoria from lesion of, XIII:1048t, XIII:1050 Sympathomimetic agents, for glaucoma, XIII:1079 Syncope bradyarrhythmias and, XIII:720 causes of, 710b diagnosis and treatment of, 709-712 in cats, 712 in Doberman pinschers, 801-802 signs associated with, 711t treatment for, 712t Synotic, for acral lick dermatitis lesions, 472 Synovial fluid Synthetic T3, 189 Syringomyelia, diagnosis and treatment of, 1102-1107, 1102f, 1103f, 1105f, 1106f Syrup of ipecac, for toxicities, 96, 97f, 113t Systemic histiocytosis, diagnosis and treatment of, XIII:589-590 Systemic inflammatory response syndrome and disseminated intravascular coagulation, XIII:190 bacterial translocation and, XIII:201 (See also EVOLVE)

  Index Systemic inflammatory response (Continued ) in cats, XIII:100 pancreatitis and, 535 shock and, 2, XIII:141 use of colloids for, XIII:135 use of glucocorticoids with, 1231-1232 Systemic lupoid onychodystrophy use of pentoxifylline with, 399 Systemic lupus erythematosus causing blepharitis, 1182 causing retinal detachment, 1216 diagnosis and treatment of, XIII:514-516, XIII:514t nonsteroidal immunosuppressive therapy for, XIII:536 T T cell inhibitors, for ocular diseases, 1152-1153 T20, for feline retrovirus, 1281t, 1282-1283 T4 (free), measurement of, XIII:323-324 Tachyarrhythmias. See also under Arrhythmias cardioversion for, 739-743 in cats, 731-739, 733t, 746f supraventricular, 722-727, 724f, 725f, 725t in cats, 736, 736f ventricular, 727-731 Tachycardia supraventricular (See under Arrhythmia, Wolff-Parkinson-White syndrome) ventricular (See Arrhythmia, ventricular) Tacrolimus as immunosuppressive agent, 256-257 for atopy, 421-422 for cutaneous vasculitis, 423 for feline pruritus, 409 for ocular diseases, 1152-1153, 1152t for perianal fistulas, 423, 468, 529 safety concerns of, 423-424 topical, 421-423 Tadalafil (Cialis), for pulmonary hypertension, 701 Tamoxifen, for mammary cancer, 365-366 Tamsulosin, for urinary retention, 956t Tannic acid, for house dust mite control, 427 Tansy essential oil, 152t Tapazole. See Methimazole Tar shampoos, 412t, 413 Tarsorrhaphy, partial, for keratoconjunctivitis sicca, XIII:1065 Taurine blood levels of, XIII:763 deficiency of, 779t causing reproductive disorders in the queen, 1044 in American Cocker spaniels, XIII:761-762 in canine dilated cardiomyopathy, 707-708, 796 in feline dilated cardiomyopathy, 707, 814 for feline myocardial failure, XIII:763, XIII:765 for heart failure, XIII:750 for hepatic lipidosis, 573 role of, in heart disease, XIII:714 Tea ingestion, 110 Tea tree oil toxicity, 120b, 123 Tear film breakup time, 1193-1195 film disturbances, 1193-1196 replacement products, 1195-1196 staining, XIII:1055 substitutes, XIII:1063, XIII:1064t Teeth. See Dental disease Temperature. See Fever; Hyperthermia; Hypothermia Temporary cardiac pacing, 43-47 Tendon disorders, supraspinatus, 1117-1120, 1118f Tenosynovitis, empiric antimicrobial therapy for, 1228-1229 Tension pneumothorax, 687, XIII:826 Tepoxalin (Zubrin), for neurologic and musculoskeletal pain, 1128t

1383

Terbinafine for dermatophytosis, 460t, 461 for fungal rhinitis, 614 for Malassezia infections, 455t, 456 otic therapy, 431t Terbutaline adverse effects of, 644 for chronic bronchitis in cats, 650-651, 654-655 in dogs, 644 for feline asthma, 650, 654-655, XIII:808 for tracheal collapse, 634 interactions with, 653-654 toxicity of, XIII:154, XIII:154t Testes. See Testicle(s) Testicle(s), diseases of, in dogs, 942t, XIII:941-947, XIII:941t Testicular feminization syndromes, 1038-1039, XIII:907-908 Testosterone cypionate, 957t, 1028 Testosterone propionate, 957t Testosterone, for estrus suppression, 1024-1025, 1028 Tetany, hypocalcemia causing, 244 Tetracycline(s) adverse effects of, crystalluria and uroliths as, XIII:847 associated liver disease, 568t for brucellosis, 986 for episcleritis, in dogs, 1191t, 1192 for lower respiratory tract infections, 1226t, 1228 for tear film disturbances, 1196 for tear staining, XIII:1055 for urinary tract infections, 1226, 1226t in dermatology, XIII:537 Tetralogy of Fallot feline, XIII:739t, XIII:740t surgery for, XIII:747 Texas fever, 1288 Thalidomide, for feline infectious peritonitis, 1297t Thallium, XIII:208t Thebaine toxicity, 145-146 Theophylline adverse effects of, 644, 655 drug interactions with, 655 enrofloxacin, 644, XIII:803 drug monitoring of, XIII:28t for canine chronic bronchitis, 644, XIII:803 for feline asthma, 655 for feline chronic bronchitis, 655 for tracheal collapse, 634 Thiabendazole, otic therapy, 431t Thiacetarsemide adverse reactions of, in dogs, XIII:240t associated liver disease, 568t, 569 comparison of, to melarsomine, XIII:787-788 toxicity of, XIII:217-218 Thiamine deficiency of causing vestibular signs, 1100, XIII:969-970 in hepatic lipidosis, 572 supplementation of, with status epilepticus, 1063f, 1064 Thiazide diuretics causing nephrotoxicity, 160b for dilated cardiomyopathy, in dogs, 793-794 for feline cardiomyopathy, 811t, 813-814 for hypertension, XIII:840 for hypoparathyroidism, 246 Thiazolidinedione(s), for non-insulin dependent diabetes mellitus, XIII:351 Thienopyrindine(s) as antiplatelet therapy, 25 for prevention of thrombi, 695 Thiocyanate toxicity, from sodium nitroprusside, XIII:195 Thiopental (Pentothal) for laryngeal evaluation, 627-628 use of, XIII:124, XIII:125t Thioureylenes, for treatment of hyperthyroidism, XIII:334-336

1384

  Index

Thoracic duct ligation, for chylothorax, 680 with mesenteric lymphangiography, 681 Thoracic duct, role of, in chylothorax, 678 Thoracic trauma, 86-87 Thoracocentesis for pleural effusion, 675-676 for pneumothorax, 87, 685-689, 685f technique for, XIII:819-820 Thoracoscopy for diagnosis of interstitial lung disease, 673 use and technique for, XIII:157-159 (See also EVOLVE) visualization by, XIII:158t Thoracostomy tube. See Chest tube Thoracotomy for cardiopulmonary resuscitation, 29-30, XIII:148 for pneumothorax, 686-688 Thorn apple, 151t Thrombi. See Thromboembolism Thrombocytopenia. See also Platelet(s) and tests for platelet dysfunction, 292-294, 293t autoimmune hemolytic anemia and, XIII:429 cytograms and histograms of platelets demonstrating, XIII:384 diagnosis and treatment of, 281-287 differential diagnosis of, XIII:105t evaluation of patient with, XIII:438-439 from anaplasmosis, 1249 from babesiosis, 1290 from leptospirosis, 1239 from methimazole, 175 from platelet dysfunction, XIII:442-447 from renal disease, 914 immune-mediated, 281-282, 284-285, XIII:438-442 in disseminated intravascular coagulation, XIII:192 infectious, XIII:438-442 Thromboelastography (TEG), 24, 692 Thromboembolism arrhythmias with, 732 arterial, in cats, 811, 814-815, 819-824 causing pulmonary hypertension, 698-699, 698b, 702 from hyperthyroid heart disease, XIII:717, XIII:718 from infective endocarditis, 787 prevention of, 693-695 pulmonary, 689-697, XIII:433 risk of with melarsomine treatment, XIII:789 with proteinuria, 863 Thrombolysis for arterial thromboembolism, 823 for pulmonary thromboembolism, 695 Thrombopathia (thrombocytopathia). See Platelet(s), dysfunction of Thrombopoietin, use of, XIII:403, XIII:407 Thromboprophylaxis, 824 Thrombosis causing pulmonary thromboembolism, 689-697 diagnosis and treatment of, 24-28 Thromboxane, role of, in glomerulonephritis, XIII:852 Thuja essential oil, 152t Thymectomy, for autoimmune myasthenia gravis, 1110 Thymomas, mediastinal, 355-356 Thyroid carcinoma, therapy of, 182-183 Thyroid disease, diagnostic tests for, 172-173, 186-189, 188t Thyroid gland, cardiomyopathy and, XIII:716-719 See also EVOLVE Thyroid hormone(s) antithyroglobulin antibodies, 172, 189 autoantibodies to, XIII:323 effect of drug treatments on, 187t free T4, interpretation of, 172-173, 187t, 188t interpretation of diagnostic tests for, XIII:321-324 measurement of, XIII:323

Thyroid hormone(s) (Continued ) monitoring replacement of, algorithm for, XIII:332f negative feedback of, during replacement, XIII:332f thyroid-releasing hormone (TRH) test, in hypothyroidism, 188 thyroid-stimulating hormone (TSH), XIII:330-333 for monitoring hypothyroidism, XIII:333 in hypothyroidism, 186-191, 187t, 188t interpretation of tests for, 172-173 measurement of, XIII:323 thyroxine (T4) effect of radioiodine on, 181, 184 for hypothyroidism, and neurological changes, XIII:975 interpretation of, 172-174 with hypothyroidism, 186-188, 187t, 188t measurement of, XIII:322-323 monitoring of with hyperthyroidism, 177, 181, 184 with hypothyroidism, 189-191, 190f total T3, interpretation of, 172, 186-187 Thyroid ultrasound, 188 Thyroidectomy, advantages and disadvantages of, in cats, 176t Thyroiditis (canine), 185-191 Thyroxine. See Levothyroxine Ticarcillin-clavulanate (Timentin) for bacterial pneumonia, 661t for Pseudomonas spp. ear infection, 435t for sepsis, XIII:273t minimum inhibitory concentrations (MIC) of, XIII:35t Tick control product(s) active ingredients in, XIII:232t toxicity of, XIII:231-235 Tick paralysis, vector associated with, XIII:297t Tick(s). See also Rickettsial infection(s); specific disorder e.g. Lyme disease as vectors for anaplasmosis, 1249, 1251 for babesiosis, 1288, 1289t for Bartonella vinsonii, XIII:300, XIII:301t for canine hepatozoonosis, XIII:310-311 for disease, XIII:296-297 (See also EVOLVE) treatments for, 394 Ticlopidine as antiplatelet therapy, 25 for prevention of thrombi, 695 Tiletamine, adverse reactions of, XIII:240t, XIII:241t Timolol, for feline glaucoma, 1210t, 1211 Tirofiban, as antiplatelet therapy, 25 Tissue factor pathway inhibitors, for disseminated intravascular coagulation (DIC), 291 Tissue factor, role of, in disseminated intravascular coagulation, 287, 288f Tissue perfusion, shock and, 2-4 Tissue plasminogen activator (t-PA) for stroke, 1076 for thrombolysis, 695 Tobacco poisoning, 135-138, XIII:230 incidence of, XIII:206t nicotine content and, 136t Tobramycin causing nephrotoxicity, 162 intravitreal, 1148t minimum inhibitory concentrations of, XIII:35t subconjunctival, 1147t toxicity of, XIII:214 Tocodynamometer, 993-998, 996f, 997f Tolmetin, toxicity of, 162, XIII:214-215 Tolteridine for feline idiopathic cystitis, 947t, 948 for urinary incontinence, 959 Toluene, adverse reactions of, in cats, XIII:241t Tonka bean, 151t Tonometry, 1141-1142 Tonopen, 1142 Topical immunomodulary therapy, 420-425

Topical therapy for dermatophytosis, 459-460 for hot spots, 447-448, XIII:550-551 for Malassezia spp. infections, 456 for otitis externa, 428-433, 430t, 431t, 432t in cats, XIII:545 using immune modulators, 420-425 Topoisomerase I inhibitors, as chemotherapy, XIII:475-476 Topoisomerases, XIII:481 Total parenteral nutrition. See Parenteral nutrition Toxicity(ies). See also Drug toxicity; Plant(s); Poisoning specific agent (e.g. Ethylene glycol) acute renal failure and, XIII:173-174 alpha and beta-agonists causing, XIII:153-157 causing hepatopathy, 544b, 566-569, 567b, 568t causing pregnancy loss, 988 common household chemicals and, XIII:223-226 digoxin, XIII:751 exposures, 92-94, 93t and treatments, 95-99, 96b, 96t flea and tick products and, XIII:231-235 from insecticides, 119-125 hepatotoxins, XIII:217-219 herbal product, 149-156, 151t, 152t lawn care products and, XIII:221-222 legal considerations for, 105-108 nephrotoxins causing, XIII:212-216 non-steroidal anti-inflammatory drugs and, XIII:227-229 over-the-counter drugs causing, XIII:227-231 plants causing, XIII:220-221t recently recognized, 138-143 sources of help for, 104-105 treatment of, 112-116, 114t, 116t, XIII:207-211, XIII:207t urban legends of common, 109-111 Toxin, induced neonatal diarrhea, XIII:627t Toxocara canis, during pregnancy, in dogs, XIII:932 Toxoplasmosis and retroviral infection, XIII:289-290 causing anterior uveitis, 1203b, 1204 causing feline myocarditis, 807 causing myositis, 1113-1115 causing pregnancy loss in the queen, 1044 diagnosis and treatment of, 1254-1258 ocular signs of, XIII:278-279 thrombocytopenia from, 283t, XIII:441t treatment of, XIII:103 use of cyclosporine with, 409 Trace elements, in parenteral nutrition, XIII:83t Trachea, tumors of, XIII:502-503, XIII:503t Tracheal collapse diagnosis and treatment of, 630-635, 638f etiology of, XIII:797f factors causing, 631f interluminal stenting for, 635-641, 637f, 638f, 639f, 640f Tracheobronchial culture, for feline asthma, XIII:807 Tracheobronchitis. See also Bordetella bronchiseptica from Bordetella bronchiseptica, 646-649 use of glucocorticoids with, 1230-1231 Tracheoscopy, 633 for tracheal collapse, XIII:798 Tracheostomy(ies) permanent, 621, 629 postoperative care of, XIII:792-794 temporary vs. permanent, XIII:793-794 Tramadol for feline idiopathic cystitis, 947t for hip dysplasia pain, 1123 for pain management, 12f-13f, 16, 1128t Transcolonic nuclear portography, of portosystemic anomalies, XIII:665f, XIII:666-667 Transcutaneous external pacing, 43-46 Transdermal medication(s), methimazole, 177-178

Transfusion(s). See Blood transfusion Transient ischemic attack, 1074 Transillumination, of the eye, 1140-1141, 1141f Transitional cell carcinoma, 369-373, 929 Transmissible venereal tumor, immunophenotyping for, XIII:506 Transplantation, renal, use of cyclosporine for, XIII:510-511 Transsphenoidal hypophysectomy, 224 Transthoracic pacing, 45f Transtracheal catheters, for oxygen delivery, 599 Transvenous catheter ablation, for supraventricular tachyarrhythmias, 726-727 Transvenous pacing, XIII:197-200 Transvenous temporary pacing, 46-47, 46f Trauma. See also Critical care; Emergency care; specific disorder e.g. Fracture brain injury from, 33-37 conjunctivitis from, XIII:1054 ocular tumors from, 1157 pancreatitis from, 536, 539 pelvic, XIII:1023-1026, XIII:1026-1032 pregnancy loss in the queen from, 1045 retinal detachment from, 1215 shearing and degloving wounds from, XIII:1032-1035 splenic, XIII:522 thoracic, 86-87 Traumatic myocarditis, 804-808, 805t Traumatic pneumothorax, 685-687 Travasol, 19 Treatment, enhancing compliance of, XIII:21-26 Trials, clinical, in oncology, 297-300, 298t Triamcinolone comparison of, to other glucocorticoids, 401t for episcleritis, in dogs, 1191t, 1192 for feline pruritus, 407-408, 409 for ocular diseases, 1150t, 1151 subconjunctival, 1147t, 1206t topical otic, 432t Triazapentadiene compounds, 120b Trichiasis, 1184, XIII:1072 causing epiphora, XIII:1057 Trichography, XIII:527-528 Trichophyton spp., 457-461, XIII:577-580 Trichuris vulpis, chronic colitis and, XIII:646 Triclosan shampoos, 414, 414t Tricuspid regurgitation valvular heart disease causing, 780-786 with pulmonary hypertension, 699-700, 699f Tricuspid valve dysplasia diagnosis and treatment of, 762-765, 763f, 764f feline, XIII:739t, XIII:740t Tricyclic antidepressant drug(s) effect on thyroid function, 187t for acral lick dermatitis, 472-473, XIII:555 for feline lower urinary tract disease (FLUTD), 945b, 946 for feline pruritus, 408, XIII:543 Trientine, for copper-associated hepatitis, 562 Trifluridine, for feline herpesvirus, 1188 Triglyceride concentration in chylothorax, 679 in pancreatitis, 537 Triiodothyronine (TT3), for monitoring therapy of hypothyroidism, XIII:330-331 Trilostane causing iatrogenic hypoadrenocorticism, 231 for hyperadrenocorticism, 223, 225-226, 227 Trimethoprim-sulfa combination adverse reactions of, in dogs, XIII:240t associated liver disease, 568t drug-associated crystalluria and uroliths, XIII:847, XIII:848f effect on thyroid function, 187t for bacterial pneumonia, 661, 661t for neutropenia, XIII:269t for toxoplasmosis, 1256 for urinary tract infections, 920-921, 920t, 921t, 1226-1227 minimum inhibitory concentrations of, XIII:35t toxicity of, XIII:218

  Index Tritrichomonas, 509-512, 517 Troglitazone, use of, XIII:351, XIII:351t Trombiculids, differential diagnosis for, in cats, XIII:565t Tromethamine ethylenediaminetetraacetic, otic, 431t Tropheryma whippelii, 521 Tropicamide, for anterior uveitis, 1206t Tropisetron, for feline infectious peritonitis, 1297t Troponin (cTn) concentration, with myocarditis, 805, 806f Trypanosoma cruzi, 804, 807 Trypanosomiasis. See Chagas’ disease Trypsin-like immunoreactivity canine, 532, 535 feline, 539-540, 541, XIII:702 Tuberculosis. See Mycobacteriosis Tularemia thrombocytopenia from, 283t vector associated with, XIII:296t Tumor suppressor, gene therapy, XIII:496 Tumor(s). See also Neoplasia handling of, for diagnosis, XIII:456 local recurrence of, 323 lysis syndrome, 929 staging of, 316, 321 hemangiosarcoma, 329-330, 329b Turpentine toxicity, XIII:224, XIII:449t Tussilago farfara, 151t Tylosin for chronic colitis, 519t, 520 for inflammatory bowel disease, 505 for small intestinal bacterial overgrowth, XIII:640 responsive diarrhea, 506-509 Tympanum, ruptured, 437 Tyrosinase, role in malignant melanoma, 381 Tyrosine crystalluria, 851t U Ulceration, gastric, 497-501 Ulceroproliferative stomatitis, feline immunodeficiency virus-associated, XIII:286 Ultrasonography bladder, 371 cervical, 250 Doppler use in CPR, 32 eye, 1144, 1164 for adrenal masses, XIII:370 for biliary mucocele, 588, 588f for canine breeding management, 979 for feline urinary calculi, 932-933 for fetal monitoring, 993 for gastrointestinal neoplasia, XIII:622 for hepatobiliary disease, XIII:661 and needle biopsy, XIII:661-662 for hepatoportal microvascular dysplasia, XIII:684 for hypothyroidism, 188 for pancreatitis, 535 for parathyroid gland disease, XIII:347 for portosystemic anomalies, 583, 585f, XIII:666 for pregnancy diagnosis, 986, XIII:919-920, XIII:919f-920f, XIII:921t in the queen, 1041 for renomegaly and neoplasia, 925-930 for testicular diseases, XIII:942f, XIII:943 for tracheal collapse, 632, XIII:798 liver, 547-548, 552, 571, 577 nasopharyngeal, 623 prostatic, 1047-1048 with azotemia, 858 Ununited anconeal process, XIII:1005-1014 Urate crystalluria, 851, 851t Urate urolithiasis breeds at risk for, 857t compound, XIII:876-877, XIII:876t dietary recommendations for, XIII:843t, XIII:846, XIII:846t urine collection for, XIII:13t Urban legends of toxicity, 109-111 Ureaplasma, causing pregnancy loss, 987

1385

Uremia. See also Renal failure gastrointestinal complications of, XIII:864-866, XIII:865t Ureter, interventional radiology of, 965-967 Ureteral obstruction, XIII:868-870, XIII:868t Ureterectomy, partial, 934 Ureteroliths, XIII:868-870 diagnosis and treatment of, in cats, 931-935, 931f Ureteroneocystostomy, 934 Ureterotomy, 934 Ureteroureterostomy, 934 Ureters, ectopic, 970 Urethra effect of early neutering on, 1019-1024 forceps biopsy of, XIII:886-888 interventional radiology of, 968-971 pressure profilometry of, for sphincter incompetence, XIII:897, XIII:897f sphincter incompetence of, in male dogs, XIII:896-899, XIII:897t stenting of, 968-970 Urethral catheterization, 936-937 antegrade, 968 Urethral cauterization, 970 Urethral obstruction diuresis post, 846t feline arrhythmias from, 735, 735f diagnosis and treatment of, 951-954 from neoplasia, 929 Urethral pressure profile (UPP), 961 Urethral stenting, 966-967 Uric acid crystalluria, 851t, 853-854 Urinalysis bacterial urinary tract infection and, in cats, XIII:10-19, XIII:881-882 crystalluria and, drug-associated, XIII:846-848 excess protein in, 860-863 interpreting and managing crystalluria, 850-854 with acute abdomen, 70 with acute renal failure, XIII:174 with azotemia, 858 with feline lower urinary tract disease (FLUTD), 945, 946t with hepatobiliary disease, 546 with interstitial cystitis, XIII:894-895 with polyuria and polydipsia, XIII:833 Urinary bile acids, 547 Urinary bladder cancer breeds at risk, 369, 370t diagnosis and treatment of, 369-373 prognosis for, 372 staging of, 370, 370b, 372 Urinary bladder, interventional radiology of, 968-971 Urinary diseases calcitriol for, 892-895 crystalluria and, 850-854 diagnostic approach to azotemia from, 855-860 feline idiopathic cystitis, 944-950 glomerular filtration rate testing for, 868-871 incontinence from, 955-964 infections causing, 917-924 interventional radiology for, 965-971 obstruction causing (See Obstruction, urinary) polyuria and polydipsia with, 844-850 proteinuria and, 860-863 urethral obstruction, 951-954 uroliths, 930-943 Urinary incontinence effect of early neutering on, 1021 from urethral sphincter incompetence, XIII:897t in male dogs, XIII:896-899 injectable bulking agents for, 960-964, 962f, 970 management of, 955-959, 956t, 957t Urinary system differential diagnosis of, with acute ­abdomen, 68t effect of early neutering on, 1020-1021

1386

  Index

Urinary tract. See also under Renal disease(s); specific disorder host defenses of the, XIII:883t lower, forceps biopsy of, XIII:886-888, XIII:887f trauma of, XIII:850 Urinary tract disease. See Feline lower urinary tract disease (FLUTD) Urinary tract infection(s) bacterial, in cats, XIII:880-882, XIII:881t diagnosis and treatment of, 918-921, 919t, 920t, 921t multidrug resistant, 921-925 endocrine disorders and, in dogs, XIII:878-880 in diabetic pets, 215 methods for reducing hospital acquired, 1224 persistent, 923-924 relapsing and recurrent, 922-925 therapy of, XIII:884-886, XIII:885t empiric antimicrobial, 1226-1227, 1226t guidelines for antimicrobial treatment, XIII:879t with vulvar hypoplasia, 1014 Urine 24 hour collection of, XIII:12-14, XIII:13t antibiotic concentration in, XIII:885 cortisol, effect of nonadrenal disease on, XIII:362-363 cortisol:creatinine ratios of, 220, XIII:322 and adrenal disease testing, 172 crystal formation in, 850-854 dipstick examination for protein in, 887f diversion of, with tube cystostomy, XIII:870-871 (See also EVOLVE) factors predisposing to precipitation of drugs in, XIII:846t glucose monitoring of, 213, XIII:348-349 leptospires in, XIII:308 normal physiology of production of, 844 pH of, in timed samples, XIII:15 preservatives for, XIII:14 protein in the (See Proteinuria) quantitative collection of, XIII:12-17 retention, 955, 956t sperm in the, 1049 timed samples of, indications for, XIII:13t urine culture, in cats, XIII:881-882 volume, approximation of, XIII:17 water deprivation testing and, XIII:834 Urine acidifiers, XIII:891 Urine albumin/creatinine (UPC) ratio, 862 Urine analyte:creatinine ratios, XIII:17 Urine output, monitoring of, 53 Urine protein/creatinine (UPC) ratio, 861-862, 867 substaging of, 887t with chronic kidney disease, 877, 884-885, 886f, 887, 887f, 889t Urine specific gravity dehydration and, 49 interpretation of, 848 with proteinuria, 860-861 variables affecting, 868 Uroabdomen, 71, XIII:163 Urodynamics, 961 Urogenital anomaly(ies). See specific disorder Urohydrodistension, for feline lower urinary tract disease, XIII:893 Urohydropropulsion, retrograde, 936 Urokinase (Abbokinase), for thromboembolism, XIII:766 Urolithiasis See also individual types ammonium urate. See (under Ammonium urate) breeds at risk for, 857t calcium oxalate. See (Calcium oxalate uroliths) calcium phosphate. See (Calcium phosphate urolithiasis) causing azotemia, 856b compound, XIII:874-877, XIII:876t cystine (See Cystine urolithiasis) diagnosis and treatment of, in cats, 938f

Urolithiasis (Continued ) drug-associated, XIII:846-848 impact of drugs on formation of, XIII:846-848, XIII:846t incomplete removal of, correction of, 936-939 laser lithotripsy for, 939, 940-943 obstructive, XIII:849-850 renal nephrotomy and, XIII:867 silica (See Silica urolithiasis) struvite (See Struvite urolithiasis) surgery for, 933-935 urate (See Urate urolithiasis) urethral obstruction and, 951-954 urine crystals and, 851-852 Urologic emergencies, XIII:849-850 Ursodeoxycholic acid, for cholangiohepatitis, XIII:673-674 Ursodeoxycholic acid therapy, 563-565, XIII:691-693. See also EVOLVE for feline inflammatory liver disease, 578 for hepatic lipidosis, 573 Urticaria-angioedema, from drug hypersensitivity, XIII:556-559, XIII:557t USDA, reporting adverse drug events to, 99-104 Uterine biopsy, for anestrus, XIII:926 Uterine disease, causing pregnancy loss in queens, 1043 Uterine inertia, 994-996, 997f Uterine prolapse, 999-1000 Uterine torsion, causing pregnancy loss in the queen, 1043 Uveitis aqueous flare from, 1142, 1142f associated with systemic infectious diseases, XIII:277t causes of, 1203b corneal edema from, 1160f diagnosis and treatment of, 1178-1179, 1200-1207, 1201f-1206f from leptospirosis, 1237 from toxoplasmosis, 1257 glaucoma from, 1205, 1207, 1212, XIII:1084 miosis from, 1171 penetrating and blunt trauma causing, XIII:1092 Uveodermatologic syndrome affecting eyelids, 1183 causing retinal detachment, 1216 with anterior uveitis, 1201f, 1205f Uveodermatologic syndrome, affecting eyelids, XIII:1052 V Vaccination(s) assessment of risk and, XIII:252 for Bordetella bronchiseptica, 648-649, 1273, 1273t complications of, 649 for control of feline viral diseases, 1276t, 1279, 1300t, 1301-1305 for feline chlamydiosis, 1187 for feline immunodeficiency virus, 1276t, 1277, 1279 for feline infectious peritonitis, 1297-1298, 1303b, XIII:293 vaccination, 1303 for feline leukemia virus, 1276t, 1277, 1279 for herpesvirus-1, in cats, XIII:1059 for immunocompromised pets, recommendations for, XIII:253-256 for leishmaniasis, 1253 for leptospirosis, 1239-1240, 1273t, XIII:309-310 for Lyme disease, recommendation for, XIII:256-258 for malignant melanoma, 381 for parvovirus, XIII:631-632 for prevention of fibrosarcoma, in cats, XIII:499 fungal disease and, XIII:579 guidelines for canine, 1272-1274, 1273t guidelines for feline, 1275-1278, 1276t

Vaccination(s) (Continued ) issues regarding, XIII:250-252 pregnancy, in dogs and, XIII:932 recombinant, XIII:253 safety of, XIII:251 Vaccine reactions, XIII:251, XIII:254t fibrosarcoma from, in cats, 332-335, XIII:498-500 reporting of, XIII:252t in cats, 1275 thrombocytopenia from, XIII:440 Vaccine-associated sarcoma, 332-335, 334t Vacuum-assisted closure (VAC), of abdominal wounds, 75, 75f Vagal nerve induced syncope, 709, 801 maneuvers for supraventricular tachyarrhythmias, 723 megaesophagus from disorders of the, 487b, 488 Vagal, mediated bradyarrhythmias, XIII:720-721 Vagina, surgery of, 1012-1018 Vaginal anomalies, surgical repair of, in the bitch, 1012-1018, 1013f-1017f Vaginal band, septa and stenosis, 1016 Vaginal culture, 980-982 Vaginal cytology during false pregnancy, 980-982, 990 for feline ovarian remnant syndrome, 1040 Vaginal edema, 1016-1017 Vaginal endoscopy, 978-979 Vaginal fluid changes during cycle, 978 postpartum, 999 with pregnancy loss in queens, 1042-1043 with pyometra, 1008 with vaginitis, 1010 Vaginal hyperplasia, 1016-1017, 1017f Vaginal prolapse, 1016-1018 Vaginectomy, 1016 Vaginitis diagnosis and treatment of, 1010-1011, 1011b with clitoral hypertrophy, 1015 with vaginal band, 1016 with vulvar hypoplasia, 1014 Vaginography, 1014 Vaginoplasty, 1016 Vaginoscopy, 978-979, 981 Valacyclovir, for feline herpesvirus, 1189 Validity, of information, guides to, XIII:4-5 Valium. See Diazepam (Valium) Valsalva leak point pressure (VLPP), 961 Valvular heart disease. See also under Mitral; Tricuspid specific condition e.g. Mitral regurgitation, Endocardiosis asymptomatic, 776 dog with murmur, 781, 783 classification and staging of, 770-774 complications of, 785 diagnosis and treatment of, 780-786 from infective endocarditis, 786-791 with concurrent respiratory disease, 785 Valvuloplasty, 785, XIII:747-748 Vanadium adverse effects of, XIII:353 use of, XIII:351, XIII:351t Vancomycin for Enterococci spp. infections, XIII:265 for sepsis, XIII:273t intravitreal, 1148t minimum inhibitory concentrations (MIC) of, XIII:35t subconjunctival, 1147t Vardenafil (Levitra), for pulmonary hypertension, 701 Vascular access for CPR, 30-31 for hemodialysis, 897 for shock therapy, 4 in cats, XIII:99 ports, 39 techniques, 38-43, 39b, 40f, 41f, XIII:118-121

Vasculitis topical immune modulators for, 422-423 use of pentoxifylline with, 399 Vasoclastic products, as tear substitutes, XIII:1064t Vasodilatation, role in syncope, 709 Vasodilator(s) for heart failure, 774-775, XIII:751 refractory, XIII:753-754 for noncardiogenic pulmonary edema, 665 for pulmonary hypertension, 700-701 for subaortic stenosis, 760-761 for systemic hypertension, 715-716 Vasolytic agent(s), for CPR, 31 Vasopexy, for urethral sphincter incompetence, XIII:898, XIII:898f Vasopressin for CPR, 31 for shock, 6-7 Vasopressor(s) for CPR, 31 for shock, 6-7 Vasotec. See Enalapril VCAA (L-Asparaginase, Vincristine, Cyclophosphamide, Doxorubicin), XIII:472 Vegetable oil, as essential fatty acid, XIII:539-540 VELCAP (Adriamycin, L-Asparaginase, Cyclophosphamide, Doxorubicin, Prednisone), XIII:472-473 Venomous bite. See Bite(s) Venous access procedure, 39b catheter maintenance, 42-43 cutdown techniques, 39-41, XIII:118-121 oxygen saturation, 4 Venous pressure. See Central venous pressure Ventilation/perfusion mismatching, 604 Ventilator therapy, 603-609 for noncardiogenic pulmonary edema, 664 Ventilatory support, 601 Ventral bulla osteotomy, for feline respiratory tract polyps, XIII:795, XIII:796f Ventral slot, XIII:996-997 Ventral traction and stabilization, XIII:997-999 Ventricular arrhythmias. See under Arrhythmia(s) Ventricular ectopic beats. See under Arrhythmia(s) Ventricular fibrillation. See under Arrhythmia(s), ventricular Ventricular premature complexes (VPC), in cats, 737-738, 738f Ventricular septal defect (VSD) diagnosis and treatment of, 748-751 in cats, XIII:739t, XIII:740t surgery for, XIII:746-747 Vesiculobullous lesions, from drug ­hypersensitivity, XIII:557t Vestibular control, normal, 1097-1098 Vestibular disease, 1097-1101, 1098t, 1099f, 1100f central, 1098t, 1100-1101 diagnosis and management of, XIII:966-971 differentiation of peripheral vs. central, 1098t hypothyroidism and, XIII:327, XIII:974 peripheral, 1098-1100, 1098t Vestibular system, anatomy of, XIII:966-967 Vestibulovaginal stenosis, 1016 Veterinary literature, sources of, XIII:3t Vetsulin, use of, in dogs, 196-197 Vidarabine, for feline herpesvirus, 1188 Video-assisted thoracoscopy (VAT), 673-674 Vinblastine administration protocol for, XIII:464 as chemotherapy, 311, XIII:467 for mast cell tumors, 376, 377b Vinca major and V. minor, 151t Vincristine administration protocol for, XIII:463-464 as chemotherapy, 311, XIII:467 for canine lymphoma, 336, 337t for feline gastrointestinal lymphoma, 342, 342t for hemangiosarcoma, 330 for thrombocytopenia, 286, XIII:440

  Index Vinorelbine (Navelbine), as chemotherapy, 312t, 313 Viral diseases causing anterior uveitis, 1203b, 1204 control of, in catteries, 1299-1305 Viral encephalitis, 1071-1072 Viral myocarditis, 804-808, 805t Viral skin disease, in cats, 441-443 Virchow’s triad, 24, 696 Virus isolation for canine influenza, 1293-1294 for feline herpesvirus, XIII:1058 Virus(es) causing pregnancy loss, 987 effectiveness of disinfectants and antiseptics against, XIII:259t incriminated in disseminated intravascular coagulation, XIII:191t Vision evaluation of, 1163-1164, 1170 pathways for, 1169f, XIII:1046f, XIII:1048f, XIII:1048t lesions in, 1172t testing for, XIII:1038-1039 Visual-evoked potentials, for evaluating blindness, 1164 Vitamin A for sebaceous adenitis, 452 toxicity, 111 Vitamin B for myopathies, 1115-1116 supplementation in liver disease, 569, 572 Vitamin B1, deficiency of, furosemide and, XIII:712 Vitamin B12 malabsorption of, XIII:418 measurement of, XIII:639 supplementation of, with exocrine pancreatic insufficiency, XIII:657 Vitamin C, for acetaminophen toxicity, 113, 114t Vitamin D and paraneoplastic hypercalcemia, 344t, 345 preparation of, for, XIII:343 supplementation of for hypocalcemia, 245-247, 245t, XIII:341 for puerperal tetany, 1002 with hyperparathyroidism, 250 toxicity, 111 Vitamin D3 analog medications, causing ­nephrotoxicity, 160b Vitamin E for hepatic fibrosis, XIII:681 for hepatic support, 554-555, 569, 572-573 in dermatology, XIII:538 supplementation of, with exocrine pancreatic insufficiency, XIII:657 Vitamin imbalances, in homemade diets, 167 Vitamin K deficiency of, with liver disease, 555, 556, 573, XIII:695 for exocrine pancreatic insufficiency, XIII:657 Vitamin K1 for rodenticide toxicosis, 113, 114t, 117-119, XIII:207t, XIII:208-209, XIII:211 supplementation of, in liver disease, 573, 579 toxicity of, 575 Vitamin(s), in parenteral nutrition deficiencies of, XIII:88 supplementation of, XIII:83t Vitreous drug therapy for, 1148, 1148t humor opacification, causing blindness, 1165 opacification, blindness from, XIII:1039 Vitreous centesis, for evaluating blindness, 1164 Vizsla(s), sebaceous adenitis in, XIII:572-573 Vogt-Koyanagi-Harada-like syndrome, affecting eyelids, 1183 Volume overload, fluid therapy and, 51-54 Voluven (Fresenine Kabi), 64-65

1387

Vomiting chronic, in dogs, 492-497 control of, in cats, 574-575 fluid therapy for, 50 from uremia, XIII:864 induction of, 112-113, 113t metoclopramide for, XIII:614-615 von Willebrand’s disease autosomal recessive inheritance of, XIII:910t diagnosis and treatment of, 277-279, XIII:434-438 genetic test for, 1057t platelet dysfunction and, XIII:442 von Willebrand’s factor effect of hydroxyethyl starch on, 64 effect of hypothyroidism on, XIII:328 factors affecting, 278 Voriconazole, for fungal rhinitis, 614 Vulva, surgery of, 1012-1013, 1013f Vulval softening, 976 Vulvar hypoplasia, 1013-1014, 1015f Vulvoplasty, 1010 VVI pacing systems, 718t, 719-721 W Warfarin (Coumadin) as anticoagulant therapy, 25 changing from heparin therapy to, 696 for aortic thromboembolism, 814, 824 for prevention of thrombi, 696 Water balance, XIII:831 intake, normal physiology of, 844 Water deprivation testing, 849-850 evaluation of, XIII:834 for diabetes insipidus, XIII:325 procedure for, XIII:833-834 Weakness, as neurologic manifestations of hypothyroidism, XIII:974 Weight gain during gestation and lactation, 1004f effect of early neutering on, 1021-1022 Weight loss for chronic bronchitis, 645 for tracheal collapse, 633 from uremia, XIII:864 strategy, 192-195 Weight shifting, 1132 Weimaraner(s) growth hormone deficiency of, XIII:519 recurrent infections in, XIII:449 West Highland white terrier, inherited copper hepatitis, 561 Western red cedar essential oil, 152t Wheat gluten contamination, 165-168 Whelpwise veterinary orders, 995f Whippet(s), avermectin toxicosis in, 125-127 Whipple’s disease, 521 Whipple’s triad, XIII:358 White willow toxicity, 152 Windhound(s), avermectin toxicosis in, 125-127 Windshield washer fluid toxicity, 134-135 Wire shielding, 127 Wobbler syndrome. See Cervical vertebral instability-malformation syndromes Wolbachia, 841 Wolff-Parkinson-White syndrome, supraventricular tachycardia and, XIII:728-729 Wood’s lamp examination, XIII:529 for dermatophytosis, 457, XIII:578 Woodworm essential oil, 152t World wide websites on infectious diseases, XIII:1114t Wormseed essential oil, 152t Wounds degloving or shearing, XIII:1032-1035 hyperbaric oxygen for, 601-602 X X-linked inheritance, in dogs, XIII:909, XIII:910t X-linked severe combined immunodeficiency (XSCID), X-linked inheritance of, XIII:910t

1388

  Index

Xanthine compound uroliths with, XIII:876t crystalluria, 851t, 854, 854f Xanthomatosis, 462-463 Xenobiotics, 159 Xerophthalmia. See Keratoconjunctivitis sicca XX sex reversal, 1035-1037, XIII:905 Xylazine adverse reactions of, in dogs, XIII:240t epidural use of, XIII:128 for canine retrograde ejaculation, 1050 for neurologic and musculoskeletal pain, 1128t use of, XIII:122 in toxicities, 97f, 113t Xylitol toxicity, 109, 139-140 Y Yersinia enterocolitica, causing neonatal ­diarrhea, XIII:626t, XIII:627t Yesterday-today-and-tomorrow plant ingestion, 140-141 Yohimbine adverse reactions of, in dogs, XIII:240t for canine retrograde ejaculation, 1050 Yorkshire terrier(s), hepatoportal microvascular dysplasia of, XIII:682-686 Yucca schidigera extracts, for flatulence, 526

Z Zafirlukast, for feline airway inflammation, 656 Zalcitabine, for feline retrovirus, 1281t Zantac. See Ranitidine (Zantac) Zanthane urolithiasis, breeds at risk for, 857t Zidovudine for feline immunodeficiency virus, XIII:287, XIII:290 for feline leukemia virus, XIII:283-284 for feline retrovirus, 1281t, 1282 Zileuton, for feline airway inflammation, 656 Zinc deficiency of, liver disease and, XIII:695 for copper-associated hepatitis, 562 for hepatic fibrosis, XIII:680t, XIII:681 malabsorption of, in bull terriers, XIII:519 plasma concentrations of, 562 responsive dermatosis, 1180-1181 Zinc acetate, for flatulence, 526 Zinc gluconate shampoos, 412t, 413, 414, 414t Zinc otic, 430t Zinc phosphide toxicosis, 93, 118-119, XIII:212 Zinc sulfate floatation, 667-671 Zinc toxicosis, 114t, 115, 855, 855b, 856b, 857, 859 treatment of, XIII:209 Zinc-responsive, dermatosis of eyelids, XIII:1052

Zolazepam, adverse reactions to, XIII:240t, XIII:241t Zoledronate, for hypercalcemia of malignancy, 346f, 347 Zollinger-Ellison syndrome, XIII:617 Zonisamide, for seizures, 1068-1069 Zoonosis. See also specific disease, e.g., Toxoplasmosis of Bartonella spp. infections, 1241-1245, XIII:303, XIII:306-307 of brucella canis, 986, 1234 of Chlamydophilia felis, 1186 of dermatophytosis, 457-461, 458b of Helicobacter-associated gastric disease, 492-497 of leishmaniasis, 1252-1254 of leptospirosis, 1239-1240 of methicillin-resistant Staphylococcus aureus, 449-450 of mycobacteriosis, XIII:1116-1118 of pet birds, XIII:1113-1116, XIII:1114t-1115t of rabies, XIII:294-295 (See also EVOLVE) of salmonella, XIII:1123-1125 with reptiles, XIII:1187 of toxoplasmosis, 1257-1258, 1257b, XIII:313-314 Zymox otic, 430t