Compendium | March 2009

VOLUME 31 NUMBER 3 MARCH 2009

Compendium CompendiumVet.com | Peer Reviewed | Listed in MEDLINE

6 CE Contact Hours

FREE

CE

Vol 31(3) March 2009

CONTI N U I NG EDUCATION FOR VETERI NARIANS ®

Vomiting Treatment Options

COMPENDIUM CONTINUING EDUCATION FOR VETERINARIANS®

Understanding Behavior

Stress-Induced Hypersensitivity in Cats FREE

CE

Squamous Cell Carcinoma

PAGES 97–144

Di s Pr Re clos actic st ing e M or M an i a Se ng ed ge e P Cl ic me n ag ie al e 1 nt E t 05 Tr rro us rs t :

Refereed Peer Review

THE PARTY’S OVER FOR

TO

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March 2009 Vol 31(3) CompendiumVet.com | Peer Reviewed | Listed in MEDLINE

EXECUTIVE EDITOR Tracey L. Giannouris, MA 800-426-9119, ext 52447 | tgiannouris@vetlearn.com MANAGING EDITOR Kirk McKay 800-426-9119, ext 52434 | kmckay@vetlearn.com Subscription inquiries: 800-426-9119, option 2.

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97

March 2009 Vol 31(3) CompendiumVet.com | Peer Reviewed | Listed in MEDLINE

EDITORIAL BOARD Anesthesia Nora S. Matthews, DVM, DACVA Texas A&M University

Internal Medicine Dana G. Allen, DVM, MSc, DACVIM Ontario Veterinary College

Cardiology Bruce Keene, DVM, MSc, DACVIM North Carolina State University

Internal Medicine and Emergency/ Critical Care Alison R. Gaynor, DVM, DACVIM (Internal Medicine), DACVECC North Grafton, Massachusetts

Clinical Chemistry, Hematology, and Urinalysis Betsy Welles, DVM, PhD, DACVP Auburn University

EDITOR IN CHIEF Douglass K. Macintire, DVM, MS, DACVIM, DACVECC

Department of Clinical Sciences College of Veterinary Medicine Auburn University, AL 36849

Dentistry Gary B. Beard, DVM, DAVDC Auburn University R. Michael Peak, DVM, DAVDC The Pet Dentist—Tampa Bay Veterinary Dentistry Largo, Florida Emergency/Critical Care and Respiratory Medicine Lesley King, MVB, MRCVS, DACVECC, DACVIM University of Pennsylvania Endocrinology and Metabolic Disorders Marie E. Kerl, DVM, ACVIM, ACVECC University of Missouri-Columbia

EXECUTIVE ADVISORY BOARD MEMBERS Behavior Sharon L. Crowell-Davis, DVM, PhD, DACVB The University of Georgia Dermatology Craig E. Griffin, DVM, DACVD Animal Dermatology Clinic San Diego, California Wayne S. Rosenkrantz, DVM, DACVD Animal Dermatology Clinic Tustin, California Nutrition Kathryn E. Michel, DVM, MS, DACVN University of Pennsylvania Surgery Elizabeth M. Hardie, DVM, PhD, DACVS North Carolina State University

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CompendiumVet.com m

Epidemiology Philip H. Kass, DVM, MPVM, MS, PhD, DACVPM University of California, Davis Exotics Avian Thomas N. Tully, Jr, DVM, MS, DABVP (Avian), ECAMS Louisiana State University Reptiles Douglas R. Mader, MS, DVM, DABVP (DC) Marathon Veterinary Hospital Marathon, Florida Small Mammals Karen Rosenthal, DVM, MS, DABVP (Avian) University of Pennsylvania Feline Medicine Michael R. Lappin, DVM, PhD, DACVIM (Internal Medicine) Colorado State University Margie Scherk, DVM, DABVP (Feline Medicine) Cats Only Veterinary Clinic Vancouver, British Columbia Gastroenterology Debra L. Zoran, DVM, MS, PhD, DACVIM (Internal Medicine) Texas A&M University Infectious Disease Derek P. Burney, PhD, DVM Gulf Coast Veterinary Specialists Houston, Texas

Nephrology Catherine E. Langston, DVM, ACVIM Animal Medical Center New York, New York Neurology Curtis W. Dewey, DVM, MS, DACVIM (Neurology), DACVS Cornell University Hospital for Animals Oncology Ann E. Hohenhaus, DVM, DACVIM (Oncology and Internal Medicine) Animal Medical Center New York, New York Gregory K. Ogilvie, DVM, DACVIM (Internal Medicine and Oncology) CVS Angel Care Cancer Center and Special Care Foundation for Companion Animals San Marcos, California Ophthalmology David A. Wilkie, DVM, MS, DACVO The Ohio State University Parasitology Byron L. Blagburn, MS, PhD Auburn University David S. Lindsay, PhD Virginia Polytechnic Institute and State University Pharmacology Katrina L. Mealey, DVM, PhD, DACVIM, DACVCP Washington State University Rehabilitation and Physical Therapy Darryl Millis, MS, DVM, DACVS University of Tennessee Surgery Philipp Mayhew, BVM&S, MRCVS, DACVS Columbia River Veterinary Specialists Vancouver, Washington C. Thomas Nelson, DVM Animal Medical Center Anniston, Alabama Surgery and Orthopedics Ron Montgomery, DVM, MS, DACVS Auburn University Toxicology Tina Wismer, DVM, DABVT, DABT ASPCA National Animal Poison Control Center Urbana, Illinois

AMERICAN BOARD OF VETERINARY PRACTITIONERS (ABVP) REVIEW BOARD Kurt Blaicher, DVM, DABVP (Canine/Feline) Plainfield Animal Hospital Plainfield, New Jersey Canine and Feline Medicine Eric Chafetz, DVM, DABVP (Canine/Feline) Vienna Animal Hospital Vienna, Virginia Canine and Feline Medicine Henry E. Childers, DVM, DABVP (Canine/Feline) Cranston Animal Hospital Cranston, Rhode Island Canine and Feline Medicine David E. Harling, DVM, DABVP (Canine/Feline), DACVO Reidsville Veterinary Hospital Reidsville, North Carolina Canine and Feline Medicine, Ophthalmology Jeffrey Katuna, DVM, DABVP Wellesley-Natick Veterinary Hospital Natick, Massachusetts Canine and Feline Medicine Robert J. Neunzig, DVM, DABVP (Canine/Feline) The Pet Hospital Bessemer City, North Carolina Canine and Feline Medicine

Compendium is a refereed journal. Articles published herein have been reviewed by at least two academic experts on the respective topic and by an ABVP practitioner.

Any statements, claims, or product endorsements made in Compendium are solely the opinions of our authors and advertisers and do not necessarily reflect the views of the Publisher or Editorial Board.

CE

E Each CE article is accredited for 3 contact hours by A Auburn University College of Veterinary Medicine.

Features 105

March 2009 Vol 31(3)

CompendiumVet.com | Peer Reviewed | Listed in MEDLINE

Disclosing Medical Errors: Restoring Client Trust ❯❯ Kathleen A. Bonvicini, Daniel O’Connell, and Karen K. Cornell Discussing medical errors with affected clients can ultimately benefit your practice. This article provides tips on creating a protocol for resolving medical errors.

122

Vomiting FREE

❯❯ Héctor J. Encarnación, Joshua Parra, CE Erick Mears, and Valerie Sadler Antiemetic drugs act by affecting neurotransmitter–receptor interactions in many areas of the body. Learn why different drugs are used for different causes of vomiting.

133

Squamous Cell Carcinoma

FREE

CE

❯❯ Julie L. Webb, Rachel E. Burns, Holly M. Brown, Bruce E. LeRoy, andd C Carrie i EE. KKosarek The authors review the causes, diagnosis, and treatment of this tumor type.

Departments Cover image © 2009 Michael Woodruff/Shutterstock.com

100 CompendiumVet.com 102 The Editor’s Desk: Meet Our New Online CE “Sister” ❯❯ Tracey L. Giannouris

Understanding Behavior 116 Feline Hyperesthesia Syndrome ❯❯ John Ciribassi The etiology of feline hyperesthesia syndrome can be difficult to determine.

Behavior modification and medications may help in treatment.

104 Clinical Snapshot Pruritus in a Great Dane ❯❯ Karen A. Moriello 113 Letters 132 Product Forum 143 Index to Advertisers

Clinical Snapshot PAGE 104

143 Market Showcase 143 Classified Advertising

Compendium: Continuing Education for Veterinarians®

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March 2009 Vol 31(3)

WEB EXCLUSIVES

CE ARTICLES WEB EXCLUSIVE

VIDEOS

❯❯ Laparoscopic Gastropexy Three videos show some aspects of the techniques described in the February 2009 Surgical Views column, “LaparoscopicAssisted and Laparoscopic Prophylactic Gastropexy: Indications and Techniques.”

❯❯ Canine Thoracolumbar Intervertebral Disk Disease: Pathophysiology, Neurologic Examination, and Emergency Medical Therapy ❯❯ John F. Griffin IV, Jonathan M. Levine, and Sharon C. Kerwin Thoracolumbar intervertebral disk disease (IVDD) is a common, important cause of paraspinal hyperesthesia, pelvic limb ataxia, paraparesis, paraplegia, and urinary and fecal incontinence in dogs. Recent research offers new insights into the pathophysiology, diagnosis, prognosis, and treatment of this disorder. The comparative efficacy of many familiar therapies remains unknown and controversial. This article reviews the pathophysiology and epidemiology of this condition and the examination and emergency medical therapy of dogs with suspected thoracolumbar IVDD.

❯❯ Canine Thoracolumbar Intervertebral Disk Disease: Diagnosis, Prognosis, and Treatment ❯❯ John F. Griffin IV, Jonathan M. Levine, Sharon C. Kerwin, and Robert C. Cole Thoracolumbar intervertebral disk disease (IVDD) is a common, important cause of paraspinal hyperesthesia, pelvic limb ataxia, paraparesis, paraplegia, and urinary and fecal incontinence in dogs. This article addresses the diagnosis, prognosis, and treatment of dogs with thoracolumbar IVDD.

CLINICAL SNAPSHOT

❯❯ Pekinese With Acute Onset of Collapse

NEWS BITES

❯❯ Vet Study Finds Aggressive Owners Have Aggressive Dogs A University of Pennsylvania study has found that most aggressive dogs will remain aggressive when dog owners use confrontational or aversive methods to try to train their pets.

❯❯ Economy Means Slowdown for Some Vet Practices A number of small animal practices have reported a drop in client visits.

❯❯ New SPCA Vet Hospital a San Francisco Treat The $29-million Leanne B. Roberts Animal Care Center is the new home of the San Francisco SPCA’s nonprofit veterinary hospital, spay/neuter clinic, and shelter medicine program.

❯❯ Beware of Cocoa Mulch A popular option for landscaping, cocoa mulch can be deadly to pets.

E-NEWSLETTER ❯❯ COMPENDIUM EXTRA Our monthly e-newsletter provides Web Exclusive articles and news, as well as a preview of this month’s journal. Sign up at CompendiumVet.com.

CONTACT US ❯❯ Email your questions, suggestions, corrections, or letters to the editor: editor@CompendiumVet.com

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CompendiumVet.com

The potential for an animal poison emergency is always there, so we are too.

A pill bottle accidently knocked off a sink. Everyday things can quickly become a poison emergency for a pet. It’s the reason the ASPCA® Animal Poison Control Center is here 24/7/365 to support you with critical recommendations. As the only center in North America dedicated solely to animals, we have an experienced team of board certified veterinary toxicologists* on staff with the special expertise needed to save a pet’s life.

Our exclusive AnTox™database of more than one million cases of animal poisonings also gives us immediate access to crucial case information. When potential danger turns into a real emergency, don’t hesitate. Call us.

ORDER A FREE MAGNET Visit www.aspca.org/freemagnet for your free ASPCA Animal Poison Control Center magnet − an easy way to keep our emergency number handy.

For information on our online Toxicology CE courses, visit www.apcc.aspca.org.

No animals were harmed during the production of this ad.

ASPCA_Beagle_8.75x10.indd 1

*American Board of Veterinary Toxicology www.abvt.org

Vet Tech | Trim: 8 x 10 3/4 | Live: 7 x 9 3/4 | Bleed: 8 1/4 x 11

12/7/07 6:25:23 PM

The Editor’s Desk ❯❯ Tracey L. Giannouris, MA, Executive Editor

Tracey with her son, Michael Francis

Meet Our New Online CE “Sister”

F

or more than 30 years, Compendium has 145,000 registered users (43.3% of whom are been your trusted source for continuing practicing veterinarians; 47.7%, veterinary techeducation (CE), both in print and, more nicians; 3%, veterinary technician students; and recently, on the Internet. Now, all of us here 1.2%, veterinary students) visit VetLearn.com. at Compendium are pleased to announce the While there, they investigate a total of 200,000 expansion of our CE efforts with the launch of a pages (40,000 of which are clinical CE review new Web site: CECenter.com. articles) and obtain a total of 2,000 CE credits.

CECenter.com, a companion site to VetLearn. Based on these numbers, we saw a clear need to com (which comprises CompendiumVet.com, expand our CE offerings by creating a companCompendiumEquine.com, SOCNewsletter.com, ion portal dedicated to “all things CE.” VetTechJournal.com, VeterinaryTherapeutics.com, CECenter.com gives both veterinarians and and ForumVet.com), is devoted exclusively to provid- veterinar y technicians the ability to search ing interactive online CE to veterinarians and veteri- for and participate in CE activities. In addition nary technicians. The mission behind the site is to to the archive of our own peer-reviewed artiprovide veterinary practitioners with new, timely cles, CECenter.com offers exclusive, interactive, information that can be immediately incorporated sponsored courses accredited by the Registry into practice. To achieve this goal, we have gathered of Approved Continuing Education, as well in one central location a wide array of CE activities, as a complete list of CE requirements by state from peer-reviewed CE content from Compendium, and links to CE programs from other respected Compendium Equine, and Veterinary Technician to sources such as the AVMA, the American Animal presentations given by recognized experts.

Hospital Association, and accredited universities Our realization of the need for a dedicated and institutions. Other features of CECenter.com veterinary CE portal crystallized with our rec- include a preview of upcoming courses and activognition of the increasing number of veterinary ities. Users get individual accounts that contain a practitioners who are using the VetLearn.com and permanent online record of their CE history and CompendiumVet.com sites to meet CE require- allow them to reprint any CE certificate at any ments. In an average month, approximately time. And our plans call for more CE offerings— and more CE-related features and content—as CECenter.com grows throughout 2009.

CECenter.com is accessible to everyone registered on VetLearn.com or CompendiumVet.com, and registration is free. If you haven’t already registered, we invite you to sign up now so that you can explore CECenter—and our other sites—for yourself. We are confident that, along with CompendiumVet.com, CECenter.com will become the preferred online CE source for you and your technician staff.

As always, we welcome your feedback, comments, and suggestions for both VetLearn.com and CECenter.com. Please feel free to email me at tgiannouris@vetlearn.com.

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Compendium: Continuing Education for Veterinarians® | March 2009 | CompendiumVet.com

T:8” L:7”

LET YOUR LETYOUR CONSCIENCE SCIENCE GUIDE YOU. L:9.75”

Veterinarians also believe that INTERCEPTOR® (milbemycin oxime) Flavor Tabs® provide better science and value for the money than Heartgard.2

Dogs and Cats should be tested for heartworm prior to use. In a small percentage of treated dogs, digestive and neurologic side effects may occur. In cats, safety studies at up to 10 times the label dose did not detect any adverse drug reactions. Please see brief summary on page XX 104for formore moreinformation. information.

Milbemycin oxime. Parasiticide Usage Study, June 2005. Data on file. Novartis Animal Health US, Inc. Data on file. Novartis Animal Health US, Inc. ©2009 Novartis Animal Health US, Inc. INTERCEPTOR and Flavor Tabs are registered trademarks of Novartis AG. Heartgard is a registered trademark of Merial Ltd.

1 2

43955_Interceptor_Ad_I2.indd 1

2/12/09 2:45:59 PM

T:10.75”

Milbemycin oxime is trusted #1 by veterinarians for use on their own dogs.1

Clinical Snapshot Particularly intriguing or difficult cases

Case Presentation #1

TO LEARN MORE

❯❯ Karen A. Moriello, DVM, DACVD, University of Wisconsin-Madison This Great Dane (A) was one of 12 dogs in a kennel, all of which had had intense pruritus for 1 year. The owners reported that the other dogs looked similar and that all the dogs were losing weight and were irritable with the owners and each other. Close examination of the skin revealed a generalized papular eruption without evidence of pustules or epidermal collarettes. Any manipulation of the skin triggered an intense episode of self-mutilation. All the dogs were currently vaccinated and received monthly heartworm medication and monthly spot-on flea control.

The owners reported no lesions or discomfort after handling the dogs. Flea combings were negative. Skin scrapings revealed the organism shown (B).

1. What is the diagnosis?

2. The owners of the kennel have three

border collies and seven cats in addition to these dogs. What are the treatment options for this kennel of dogs?

3. A similarly named condition occurs in cats. What is the cause, and what treatment can be used for this condition?

Clinical Snapshot presents illustrated case histories and challenges you to answer the questions posed. This case is part of the series of Self-Assessment Colour Review books on multiple topics from Manson Publishing Ltd., London, available from Blackwell Publishing Professional.

SEE PAGE 114 FOR ANSWERS AND EXPLANATIONS.

For more information or to obtain any of the

A

books in the series, call 800-862-6657 or visit BlackwellProfessional.com

B

INTERCEPTOR Flavor Tabs are palatable and most often will be consumed by the dog or cat when offered by the owner.

As an alternative, the dual-purpose tablet may be offered in food or administered as other tablet medications. Watch the dog or cat closely following dosing to be sure the entire dose has been consumed. If it is not entirely consumed, redose once with the full recommended dose as soon as possible.

NADA 140-915, Approved by FDA INTERCEPTOR® (milbemycin oxime) Flavor Tabs® for Dogs and Cats Brief Summary—For full product information see product insert.

Caution: Federal (USA) law restricts this drug to use by or on the order of a licensed veterinarian.

Indications and Usage: INTERCEPTOR Flavor Tabs for dogs are indicated for use in the prevention of heartworm disease caused by Dirofilaria immitis, the control of adult Ancylostoma caninum (hookworm), and the removal and control of adult Toxocara canis and Toxascaris leonina (roundworms) and Trichuris vulpis (whipworm) infections in dogs and in puppies four weeks of age or greater and two pounds body weight or greater. INTERCEPTOR Flavor Tabs are indicated for use in the prevention of heartworm disease caused by Dirofilaria immitis, and the removal of adult Ancylostoma tubaeforme (hookworm) and Toxocara cati (roundworm) in cats and kittens six weeks of age or greater and 1.5 lbs. body weight or greater.

Dosage and Administration: Dogs: INTERCEPTOR Flavor Tabs for Dogs are given orally, once a month, at the recommended minimum dosage rate of 0.23 mg milbemycin oxime per pound of body weight (0.5 mg/kg).

Recommended Dosage Schedule for Dogs Body Weight INTERCEPTOR Flavor Tabs 2–10 lbs.

11–25 lbs.

26–50 lbs.

51–100 lbs.

One tablet (2.3 mg) One tablet (5.75 mg) One tablet (11.5 mg) One tablet (23.0 mg)

Dogs over 100 lbs. are provided the appropriate combination of tablets.

Cats: INTERCEPTOR Flavor Tabs for Cats are given orally, once a month, at the recommended minimum dosage rate of 0.9 mg milbemycin oxime per pound of body weight (2.0 mg/kg).

Recommended Dosage Schedule for Cats Body Weight INTERCEPTOR Flavor Tabs 1.5–6 lbs.

6.1–12 lbs.

12.1–25 lbs.

One tablet (5.75 mg) One tablet (11.5 mg) One tablet (23.0 mg)

Cats over 25 lbs. are provided the appropriate combination of tablets.

104

INTERCEPTOR Flavor Tabs must be administered monthly, preferably on the same date each month. The first dose should be administered within one month of the dog or cat’s first exposure to mosquitoes and monthly thereafter until the end of the mosquito season. If a dose is missed and a 30-day interval between dosing is exceeded, administer INTERCEPTOR Flavor Tabs immediately and resume the monthly dosing schedule.

If INTERCEPTOR Flavor Tabs replace diethylcarbamazine (DEC) for heartworm prevention in dogs, the first dose must be given within 30 days after the last dose of DEC. Warnings: Not for human use. Keep this and all drugs out of the reach of children.

Precautions: Dogs: Do not use in puppies less than four weeks of age and less than two pounds of body weight. Prior to initiation of the INTERCEPTOR Flavor Tabs treatment program, dogs should be tested for existing heartworm infections. Infected dogs should be treated to remove adult heartworms and microfilariae prior to initiating treatment with INTERCEPTOR Flavor Tabs.

Mild, transient hypersensitivity reactions manifested as labored respiration, vomiting, salivation, and lethargy may occur after treatment of dogs carrying a high number of circulating microfilariae.

Cats: Do not use in kittens less than six weeks of age or less than 1.5 lbs. body weight. Safety in heartworm positive cats has not been established. Safety in breeding, pregnant, and lactating queens and breeding toms has not been established.

Adverse Reactions: The following adverse reactions have been reported following the use of INTERCEPTOR in dogs: depression/lethargy, vomiting, ataxia, anorexia, diarrhea, convulsions, weakness, and hypersalivation.

Efficacy: Dogs: INTERCEPTOR Flavor Tabs eliminate the tissue stage of heartworm larvae and the adult stage of hookworm ( Ancylostoma caninum), roundworms ( Toxocara canis, Toxascaris leonina ), and whipworm ( Trichuris vulpis) infestations when administered orally according to the recommended dosage schedule.

Cats: INTERCEPTOR Flavor Tabs for Cats eliminate the tissue stage of heartworm larvae and hookworm (Ancylostoma tubaeforme ) and roundworm ( Toxocara cati ) infections when administered orally according to the recommended dosage schedule.

For technical assistance or to report suspected adverse events, call 1-800-332-2761.

Manufactured for: Novartis Animal Health US, Inc. Greensboro, NC 27408, USA ©2008 Novartis Animal Health US, Inc. INTERCEPTOR and Flavor Tabs are registered trademarks of Novartis AG. NAH/INT-FT/BS/5

Compendium: Continuing Education for Veterinarians® | March 2009 | CompendiumVet.com

06/08

©2009 Monkey Business Images/Shutterstock.com

Disclosing Medical Errors: * Restoring Client Trust ❯❯ Kathleen A. Bonvicini, EdD, MPHa Institute for Healthcare Communication New Haven, Connecticut

❯❯ Daniel O’Connell, PhDa Institute for Healthcare Communication Seattle, Washington

❯❯ Karen K. Cornell, DVM, PhD, DACVS The University of Georgia Athens, Georgia

At a Glance Case Scenario Page 105

Ethics, Values, and Moral Compass Page 105

Disclosure and Resolution: A Protocol Page 106

What to Do When an Error Occurs Page 108

Guidelines for Disclosure Page 110

Establish Practice Protocol Page 112

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he purpose of this article is to help Your nephew says, “I feel terrible—what veterinarians reach a mutually satis- should I tell my clients?” fying resolution with clients when individual, team, or system errors result in How would you respond? What one an adverse outcome. It offers a model that piece of advice would you give to your integrates the ethics of veterinary medi- nephew? cine with specific skills and attitudes that have been shown to promote psychologic Ethics, Values, and Moral Compass and practical resolution of these situations In examining this scenario and considering your own opinions, you are likely for clients and veterinary practices. relying on the values that guide the way Case Scenario you practice veterinary medicine. Still, this Consider the following1: will be a very tough conversation to have.

Many clinicians report feelings of shame, Your nephew, a recent veterinary school heartbreak, and vulnerability in situations graduate who is newly employed at a pri- like this one. Our natural instinct for selfvate small animal hospital, calls you for preservation, coupled with advice we may advice. Four days ago, he admitted a dog have received previously, can tempt us to to the hospital for vaccinations and board- be very guarded when talking with clients ing. During the admission process, he about adverse outcomes and to use caladministered a Bordetella bronchiseptica culated omissions and rationalizations to vaccine to the dog. The dog died this morn- conceal evidence of an error. In the above ing. In retrospect, your nephew realizes scenario, one might argue that vaccination that he picked up a syringe of intranasal has inherent risks. A frightened young vetB. bronchiseptica vaccine that still had a erinarian might be attracted to such seducneedle on it from being drawn from the tive reasoning as, “Disclosing the actual vial, then gave the vaccine subcutaneously. cause of death will increase the clients’ disThis inappropriate route of administration tress and certainly will not bring back the resulted in the development of liver failure animal. What good could come from tellwhile the dog was boarded at the hospital. ing the clients what really happened?”

*Adapted with permission from Compendium Equine 2008;3(1):14-22. a Drs. Bonvicini and O’Connell disclose that their nonprofit foundation receives funding from Bayer Animal Health.

Rationale for Openness The ethical positions of organizations such as the American Medical Association,2 the American College of Physicians,3 and the

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Disclosing Medical Errors: Restoring Client Trust Joint Commission4 have clear statements that require accurate disclosure of adverse medical outcomes in human medicine. Similar ethical positions exist in veterinary medicine.5 Research in human medicine and other professions6–10 has described the potential advantages of a more open approach with patients, families, and “customers” in these situations.

When applied to veterinary medicine, these benefits include the following: More situations can be worked out directly between the veterinarian, the client, and the insurance carrier without stimulating legal action or formal complaints to licensing boards.

The AVMA Professional Liability Insurance Trust (PLIT) recommends that veterinarians call the PLIT office as soon as possible after an event that could give rise to a claim.b Rebuilding rapport and trust and resolving disagreements can turn initial client disappointment into an even stronger relationship.

When the practice and the insurance carrier are willing to initiate discussion of fair settlements with clients who have been legitimately affected by errors in practice, the dollar amounts tend to be easier to negotiate and more reasonable than those obtained through legal action7,8,11 because client bitterness is minimized and dollar amounts are focused on reasonable compensation rather than punishment.

QuickNotes Most client disappointments with veterinary outcomes are not the result of negligent care.

Adverse Outcomes and Medical Errors Adverse outcome is the term used in veterinary and human medicine to indicate unanticipated harm that results from a medical treatment rather than from a disease or condition itself.12 An ethical approach to disclosure of harm hinges on the veterinarian’s commitment to determining and then sharing the most accurate conclusions about how the harm was caused.

While sometimes fairly clear, many situations require the veterinarian to draw a bright line through a gray situation to determine whether a breach of the standard of care caused the harm (and, therefore, the harm was preventable) or whether the harm occurred in the context of care that most veterinarians would judge as reasonable in a similar instance.13,14 Practically and emotionally, this can be difficult to do, yet who is in a better position to investigate, conb

Ellis LJ. Personal communication, AVMA PLIT, 2007.

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clude, and explain than the practice where the adverse event took place?

Most client disappointments with veterinary outcomes are not the result of negligent care.

For instance, clients may have unreasonable expectations that were not adequately addressed or corrected. They may not appreciate the variability between animals or that diagnostic and treatment plans are based on probabilities rather than certainties. The clinical picture may change as additional signs emerge and the response to treatment is assessed.15 Almost every effective treatment brings with it the potential for untoward side effects and complications. Unless clients are apprised of these risks, they may mistakenly believe that similarly trained clinicians would have been able to solve the problem more quickly, with less suffering, and at a lower cost. Each of the above factors is a reminder of the importance of obtaining true owner consent, recognizing and correcting unreasonable expectations, and offering adequate explanations when diagnosis and treatment are unsuccessful, even when the standard of care is met.16

Errors and Harm in Veterinary Medicine While research into the incidence, type, and impact of errors in veterinary medicine is limited, it is clear that adverse events related to errors do occur. For instance, one small UK study17 found that 78% of recent practicing veterinary graduates surveyed reported they had made a mistake that resulted in a less-than-optimal or potentially adverse outcome for a patient. Most mistakes involved failure to conduct appropriate diagnostic tests, surgical mistakes during procedures other than neutering, and administration of inappropriate drugs or medical treatment. Forty percent reported that they had not discussed the error with the client. These mistakes caused many of the respondents considerable distress.

Disclosure and Resolution: A Protocol Research has consistently indicated that, in human medicine, patients and families typically want to hear the following from the care provider when an adverse event or outcome occurs10,18–21: What happened How it happened What the immediate medical consequences are, and what impact they will have on quality of life

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Disclosing Medical Errors: Restoring Client Trust What can be done now How the problem will be prevented in the future (i.e., the promise that something good will come from the adverse event) An apology if appropriate (if errors led to the harm) The following protocol (summarized in BOX 1) provides specific approaches to assist you in organizing a thorough, appropriate, constructive response that meets the needs of the patient and the expectations of clients and that restores clients’ trust, regardless of the severity of the adverse event.

QuickNotes Emotional selfawareness is key to adopting the most constructive attitude and behavior.

Tend to the patient’s immediate clinical care.

In the event of an adverse outcome, the primary responsibility of the veterinarian is to address the needs of the patient and, if appropriate, obtain medical consultation or arrange for necessary follow-up. Consider that charges for services in these circumstances may not be billable if they are addressing conditions caused by errors (including equipment failures and system or procedural mistakes that caused harm).

Address your own emotions and needs.

Emotional self-awareness is key to adopting the most constructive attitude and behavior. A clinician who is flooded with worries about potential complaints and possible malpractice suits may be unconsciously pushed to minimize or even distort the facts and explanation offered to the client. On the other hand, the clinician who is overwhelmed with guilt

BOX 1

What to Do When an Error Occurs ©2009 Phase4Photography/Shutterstock.com

1. Care for the patient.

2. Compose yourself and investigate the details of the event.

3. Disclose to the client what occurred and apologize, if appropriate.

4. Discuss with the client the plan of care for the animal.

5. Be accountable and discuss methods of reparation.

6. Share how you plan to keep this from happening in the future.

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and heartbreak for the patient’s and client’s situation may leap to self-blame too quickly, only to have the investigation determine that no deviation from the standard of care was implicated in the outcome. There is usually enough time to consult with a trusted colleague to clarify your thinking and reestablish your emotional equilibrium before needing to make a full explanation to a client about how an adverse outcome arose.

Investigate the details of the event.

Develop clarity about what happened. The client is entitled to the most accurate understanding of what happened, which may take some time and investigation to clarify. You can ask for the client’s patience while you investigate. Make—and keep—a clear promise to discuss the conclusions when they are reached. In many cases, the cause of the harm is never fully determined; however, it remains the veterinarian’s responsibility to disclose the most likely causal pathway. Determining whether error was the cause of harm should be guided by asking,22 “What would have been expected of a similarly trained individual in that situation?”

Prepare for discussion with the client.

Start by trying to imagine and anticipate what the client may be thinking and feeling when hearing the news. O’Connell and Reifsteck23 suggest asking yourself the following selfreflection questions to help guide you in your discussion with the client: What is the most accurate explanation for the adverse event?

How would I want the situation to be handled if I were in the client’s position?

How would I feel if I suspected or later learned that the provider had not been forthright with me about the injury and its causes?

It is helpful to rehearse the actual words you will use in explaining the adverse event because hearing them will help you determine whether they are likely to be adequate to address the client’s expected thoughts and feelings.

Consider carefully who should attend the disclosure conversation. The veterinarian who is primarily responsible for the care of the animal should be there and take the lead in

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Disclosing Medical Errors: Restoring Client Trust the discussion, even if the adverse event was primarily caused by another staff member’s actions. The presence of a person who was not directly involved with the adverse event and who has credibility, maturity, and strong communication skills, such as the practice manager, can help facilitate and mediate what can be a difficult conversation. Plan when and how to begin the discussion. An initial discussion with the client should take place as soon as possible after the adverse event.

QuickNotes Disclose what you know, but guard against premature conjecture until you are as certain as you can be about causes and consequences.

Disclose to the client what occurred and apologize.

Disclose what you know, but guard against premature conjecture until you are as certain as you can be about causes and consequences.

When possible, make an initial phone call to set up an in-person meeting rather than have the discussion over the phone. If a phone disclosure cannot be prevented, start the discussion by acknowledging how sorry you are to have to be sharing the news over the phone.

In person, start the discussion by offering a frame for the information to follow: “I have some difficult news to share with you. I’m very sorry to have to tell you…”

Then explain the situation by addressing each of the issues listed above. BOX 2 offers some additional guidelines to approaching the disclosure conversation.

Elicit and acknowledge client reactions.

Frequently throughout the discussion, you should solicit the client’s perspective through questions and statements such as, “What thoughts or questions do you have about what I have explained so far?” and “I imagine you have many emotions and questions, and I want to hear from you first before going on.” Eliciting reactions serves to validate the client’s perspective on the medical error and adverse outcome and sets the stage for effective interaction.

Voice tone and body language are as important as actual words in conveying empathy for the client’s experience. Showing your “human side” through genuine expressions of empathy can strengthen the bond and trust between you and your client. An empathetic veterinarian is not defensive, even when a client expresses anger and makes accusations.

Acknowledging the client’s reaction as a legitimate one by making a statement such as, “It is normal to feel shocked and angry to learn that something like this has happened,” does not indicate that you agree with the conclusions that prompted it.

Apologize appropriately.

After an adverse event or outcome, the proper type of apology can have a powerful effect on the client, making him or her less angry and suspicious. There are two types of apology: an apology of sympathy and an apology of responsibility. An apology of sympathy is:

BOX 2

Guidelines for Disclosure 1. Choose a quiet place.

2. Ensure that there will be no distractions (e.g., turn cell phones and pagers off).

3. Provide a warning (e.g., “ I have difficult news to share.”).

4. Be attentive to your own and your client’s nonverbal messages. ❯ Make eye contact. ❯ Sit at the client’s level. ❯ Respond appropriately to client nonverbal cues (e.g., “I see that this is shocking to you.

Should I go on or do you need a moment?”).

5. Facilitate discussion and encourage questions.

6. Finish with a plan for the next contact.

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“I’m sorry this happened to you and your pet.”

An apology of responsibility is: “I am terribly sorry for this error we made that has caused more problems for your pet.”

Mazor and colleagues6,24 demonstrated that in situations in which a breach of the standard of care caused harm, respondents reported more trust and satisfaction and less likelihood of changing doctors when they received full disclosure with an apology of responsibility.

In instances in which an adverse event is not the result of medical error, an apology of sympathy is appropriate.

Compendium: Continuing Education for Veterinarians® | March 2009 | CompendiumVet.com

Disclosing Medical Errors: Restoring Client Trust Discuss the plan for care of the animal.

In many instances, by the time the disclosure conversation takes place, steps have already been taken to care for the animal, and the veterinarian is thinking about other potential consequences of the error. However, it is important to remember that the client has just received the news. Discuss the recommended plan for continuing care of the animal, including the potential short- and long-term outcomes. Often, clients are unclear about what lasting effect the error will have on their pet and may not comprehend the gravity or—in some cases—the limited impact of the error. It is critical that immediate concerns as well as the potential long-term impact be discussed in a manner the client understands.

Be accountable and offer reparation.

Finally, the practice must acknowledge responsibility to help the client recover as much as possible from the harm that has been caused.

Appropriate fees for the animal’s care should be waived. The veterinarian should anticipate discussion of who will pay for follow-up care before the disclosure conversation. Again, the AVMA PLIT recommends that it be contacted early on to discuss how best to approach this situation.

Being accountable and willing to make reparations is crucial in the disclosure process; however, it does not mean immediately offering money. Rather, it means opening up the conversation: “Can we do more to resolve this with you?

We stand ready to do what we can to help you recover from this as much as possible.”

According to the Sorry Works! Coalition,25 a leading advocacy organization for disclosure after adverse medical events, paying for errors is the ethical thing to do. However, there may be a fear that it will appear as if you are “buying” clients off. This is an understandable concern. In veterinary medicine, all of the steps of disclosure—admission of error, explanation, apology—can still be delivered sincerely, and PLIT or your liability carrier can be consulted on how to offer reparation.

Describe plans to fi x the behavior or system that contributed to the harm.

Consumers who are affected by a medical error want to know that something good has

come from the harm they have experienced.

It is unacceptable to clients to think that a veterinarian’s failure to change or reflect on the incident means that others are likely to suffer similarly.23 These sentiments become expressed as complaints to licensing boards as well as malpractice suits. Therefore, the veterinarian’s goal is to convey to the client that he or she has learned everything that can be learned from the adverse event: “I can promise you that we’ll all be meeting later today to review every step of our procedures. We want to immediately change anything that makes it more likely that this could happen again to any other animal in our care.”

Don’t rush.

Keep in mind that all these elements of disclosure may take more than one meeting or conversation to deliver effectively to the client.

Discussion of reparation may take the longest to resolve in cases in which the impact of the harm on the surviving animal and the extent of needed ongoing treatment are uncertain.

However, if a client has suffered serious loss or even financial harm (e.g., economic impact on a breeding kennel), he or she is going to want to promptly hear that you (with your liability carrier’s guidance) intend to offer fair compensation.

The heart of all effective and ethical disclosure is to provide the client with an accurate understanding of what has happened. The form an apology takes and the offers made to help a client recover from an injury caused by medical error should flow naturally from the veterinarian’s own understanding of his or her degree of responsibility for the injury.

QuickNotes The heart of all effective and ethical disclosure is to provide the client with an accurate understanding of what has happened.

Summary Consider your recommendations to your nephew in the scenario at the start of this column. Ask yourself the following questions: Are my recommendations based on ethical standards of openness, transparency, and integrity? Would I be satisfied if I were the client?

Despite our best efforts, animals will occasionally be harmed by problems that occur while they are in our or our staff’s care. Having a standard approach to disclosure and resolution that is consistent with our values, despite

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Disclosing Medical Errors: Restoring Client Trust BOX 3

©2009 Sarah Salmela/Shutterstock.com

Establish Practice Protocoll How will the practice handle an error?

Who will discuss it with the client?

Who will be present during the discussion? n??

Will individuals involved be identified?

What time frame do we recommend?

Where is the contact information for our liability carrier?

When and how will we discuss this with staff members?

the fears and vulnerabilities we are likely to feel at these times, can help us earn our clients’ forgiveness and enable us to forgive ourselves. BOX 3 lists some questions to ask when developing a disclosure protocol.

We believe in using ethical standards and values of openness and honesty as a springboard for conversations about medical errors.

However, many veterinary practices may hesi-

tate to embrace such openness for fear that it may increase malpractice risk. Acknowledging errors has been evaluated positively, leading to increased trust and lessening the possibility of negative impact7; however, clinicians may still worry about the potential costs of openness and transparency. Although disclosure discussions are difficult and may still result in formal complaints and malpractice suits, evidence8 tells us that acknowledging errors can significantly reduce litigation costs, reduce bitterness and mistrust, and avoid unnecessarily lengthy legal proceedings with the accompanying emotional pain for consumers and clinicians alike.

We encourage all veterinarians, whether joining a practice or established in one, to engage in conversations with their colleagues about the practice’s approach to and protocol for disclosure discussions in the event of a medical error. In addition, it is crucial to consult your malpractice liability insurance carrier to establish its position on the management of disclosure and resolution.

References 1. Greene CE, Schulz RD. Immunoprophylaxis. In: Greene CE, ed.

Infectious Diseases of the Dog and Cat. St. Louis: Elsevier Saunders; 2006:1097.

2. Council on Ethical and Judicial Affairs. Code of Medical Ethics—Current Opinions, 2006–2007 Edition. Chicago: American Medical Association; 2006.

3. American College of Physicians. Ethics Manual. 5th ed. Ann Intern Med 2005;142:560-582. Accessed January 2009 at www. acponline.org/ethics/ethicman5th.htm.

4. Joint Commission on Accreditation of Healthcare Organizations. 2006 Comprehensive Accreditation Manual for Hospitals: The Official Handbook. Oakbrook Terrace, IL: Joint Commission Resources; 2005.

5. American Veterinary Medical Association. Principles of Veterinary Medical Ethics. 2003. Accessed January 2009 at www.avma. org/issues/policy/ethics.asp.

6. Mazor KM, Simon SR, Yood RA, et al. Health plan members’ views about disclosure of medical errors. Ann Intern Med 2004;140(6):409418.

7. Kraman S, Hamm G. Risk management: extreme honesty may be the best policy. Arch Intern Med 1999;131:963-967.

8. Boothman R. Apologies and a strong defense at the University of Michigan Health System. Physician Exec 2006;32(7):7-10.

9. American Society for Healthcare Risk Management. Disclosure of Unanticipated Events: The Next Step in Better Communication with Patients. Chicago: American Society for Healthcare Risk Management; 2003.

10. Schneider B, Bowen DE. Understanding customer delight and outrage. Sloan Manage Rev 1999;41(1):35-45.

11. COPIC Insurance Company. A success story. COPIC’s 3Rs Program Newsletter 2007;4(2). Accessed January 2009 at www. callcopic.com/resources/custom/PDF/3rs-newsletter/vol-4-iss-2oct-2007.pdf.

12. Halbach JL, Sullivan L. Medical Errors and Patient Safety: A Curriculum Guide for Teaching Medical Students and Family Practice Residents.

New York Medical College, Department of Family Medicine; 2003. Ac-

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cessed January 2009 at www.nymc.edu/fammed/medicalerrors.pdf.

13. Nunalee MM, Weedon GR. Modern trends in veterinary malpractice: how our evolving attitudes toward non-human animals will change veterinary medicine. Animal Law 2004;10:125-161.

Accessed January 2009 at www.animallaw.info/journals/jo_pdf/ vol10_p125.pdf.

14. Wilson JF. Limited legal liability in zoonotic cases. NAVC Clin Brief May 2005. Accessed January 2009 at www.cliniciansbrief. com/?p=articles&newsid=678.

15. O’Connell D, Bonvicini KA. Addressing disappointment in veterinary practice. Vet Clin North Am Small Anim Pract 2007;37(1):135-149.

16. Bonvicini KA. Are clients truly informed? Communication tools and risk reduction. Compend Equine 2007;2(2):74-80.

17. Mellanby RJ, Herrtage ME. Survey of mistakes made by recent veterinary graduates. Vet Rec 2004;155:761-765.

18. Liebman CB, Hyman CS. A mediation skills model to manage disclosure of errors and adverse events to patient. Health Aff 2004;23:22-32.

19. Witman AB, Park DM, Hardin SB. How do patients want physicians to handle mistakes? A survey of internal medicine patients in an academic setting. Arch Intern Med 1996;156:2565-2569.

20. Lazare A. Apology in medical practice: an emerging clinical skill.

JAMA 2006;296(11):1401-1404.

21. Blendon RJ, DesRoches CM, Brodie M, et al. Views of practicing physicians and the public on medical errors. N Engl J Med 2002;347(24):1933-1940.

22. Reason J. Human Error. New York: Cambridge University Press; 1990.

23. O’Connell D, Reifsteck SW. Disclosing unexpected outcomes and medical error. J Med Pract Manage 2004;19(6):317-323.

24. Mazor KM, Simon SR, Gurwitz JH. Communicating with patients about medical errors: a review of the literature. Arch Intern Med 2004;164:1690-1697.

25. Question and answer. Sorry Works! Coalition Newsletter; December 4, 2006. Accessed January 2009 at www.sorryworks.net/ newsletter20061204.phtml.

Compendium: Continuing Education for Veterinarians® | March 2009 | CompendiumVet.com

Letters Five Common Toxins and Activated Charcoal I have a question for the author about his research for the November 2008 Pharm Profile article, “Activated Charcoal.” The article states that charcoal is contraindicated for metaldehyde ingestion. Yet it is widely accepted that it is proper protocol to give activated charcoal in these cases. In fact, in the article “Five Common Toxins Ingested by Dogs and Cats” in the same issue, charcoal is recommended as an antidote to help eliminate metaldehyde. I am curious about the discrepancy. Also, I was wondering if there is any research on UAA gel, which is mentioned in the Pharm Profile article.

Angela LeBrun, CVT Puget Sound Veterinary Referral Center & Animal Emergency Clinic, Tacoma, Washington

I have just finished reading the November 2008 journal and am puzzled by the contradiction between the paper by Drs. Luiz and Heseltine and that by Dr. El Bahri in reference to the effectiveness of activated charcoal in the treatment of ethylene glycol and metaldehyde poisonings. The former says to use it; the latter says it’s ineffective. Is there an explanation as to the correct information?

Philip T. Durfee, DVM, MPH, MVSc

The Authors’ Replies The administration of activated charcoal in the treatment of metaldehyde intoxication is controversial. Several references I consulted do not either include1,2 or recommend3,4 the administration of activated charcoal in the treatment of metaldehyde intoxication. The Handbook of Poisoning in Dogs and Cats, which is considered a veterinary toxicology reference, states, “Metaldehyde reportedly does not bind to activated charcoal and therefore use of adsorbents is not indicated.”4 On the other hand, activated charcoal has been shown to help inhibition of metaldehyde absorption in rats.5 Universal Animal Antidote (UAA) gel (Vedco, Inc. St. Joseph, Missouri) con-

tains activated hardwood charcoal and thermally activated attapulgite clay in an aqueous gel suspension. The recommended oral dosage is 1 to 3 mL/kg in dogs, cats, and large animals. The manufacturer states that the product should be shaken well before use and protected from freezing.

Lotfi El Bahri, DVM, MSc, PhD References 1. Buck WB, Osweiler GD. Metaldehyde. In: Van Gelder GA, ed. Clinical and Diagnostic Veterinary Toxicology.

2nd ed. Dubuque, IA: Kendall/Hunt Publishing Company; 1976:227-228.

2. Andreasen JR Jr. Metaldehyde toxicosis in ducklings. J Vet Diagn Invest 1993;5:500-501.

3. Booth NH, McDonald LE, eds. Veterinary Pharmacology and Therapeutics. 5th ed. Ames: The Iowa State University Press; 1982:1013-1014.

4. Campbell A. Metaldehyde. In: Campbell A, Chapman M, eds. Handbook of Poisoning in Dogs and Cats.

Oxford: Blackwell Science; 2000:181-185.

5. Shintani S, Goto K, Endo Y, et al. Adsorption effects of activated charcoal on metaldehyde toxicity in rats. Vet Hum Toxicol 1999;41(1):15-18.

I double-checked our sources about the use of activated charcoal in ethylene glycol and metaldehyde toxicoses. For ethylene glycol, we wrote, “Early diagnosis and treatment are critical for a successful outcome. Emetics should be administered if no signs are observed and the exposure occurred less than 4 hours pre-

Pharm Profile

Activated Charcoal Lotfi El Bahri, DVM, MSc, PhD École Nationale de Médecine Vétérinaire Sidi Thabet, Tunisia

Indication: Emergency treatment of acute poisoning after ingestion of a large amount of toxin or drug.

Activated charcoal—also known as active carbon, activated carbon, adsorbent charcoal, medicinal charcoal, or carbo medicinalis1—is a carbon residue derived from vegetable material (e.g., wood pulp). It is produced by exposing the original material to an oxidizing gas compound of steam, oxygen, and acids at high temperatures (900°C). This activation process creates a network of fine pores (10 to 20 nm in size) in the resulting charcoal.2 The result is a highly porous material with an enormous surface area relative to its weight.3 The adsorptive capacity of activated charcoal is a function of its binding surface area. In commercial products, the surface area varies from 1000 to 2000 m2 per gram.3,4

PHARMACOKINETICS Activated charcoal comes as a very fine, porous, black powder or granules measuring less than 1.0 mm in diameter. It does not contain any gritty material.2 It is insoluble in water and all usual solvents.1 Activated charcoal is not absorbed in the gastrointestinal tract, and all ingested activated charcoal is excreted in the feces.1 It is a stool marker, indicating that the toxin has passed through the gastrointestinal tract and no further significant toxin absorption from the original ingestion will occur.

Pharm Profile focuses on new drugs or indications in the veterinary market as well as pharmacologic products of high interest to practitioners.

Send comments/questions via email to editor@CompendiumVet.com or fax 800-556-3288.

Visit CompendiumVet.com for full-text articles, CE testing, and CE test answers.

COMPENDIUM

PHARMACOLOGY Owing to its large surface area, activated charcoal can adsorb many drugs and toxins (e.g., acetaminophen, salicylates, digoxin, organophosphate and carbamate insecticides, pyrethrins and pyrethroids, anticoagulant rodenticides, strychnine) in the upper gastrointestinal tract.1–3 It thereby facilitates the excretion of the adsorbed toxicant in the feces and reduces the amount of free agent available for absorption into the bloodstream. Activated charcoal maintains its attachment to toxins through covalent binding and van der Waals forces.5 Adsorption of substances onto charcoal is a reversible process, with rapid adsorption and slow desorption. Optimal adsorption occurs when the ratio of charcoal to toxin is 10:1 or higher.6 Administration of activated charcoal can lead to a 30% to 40% drop in digoxin levels within 12 to 18 hours.7 In one canine study, oral administration of activated charcoal solution (2.5 g/kg) 30 minutes after a single oral dose of carprofen (16 mg/kg) effectively decreased the maximum plasma carprofen concentration (85.9 ± 11.9 mg/L to 58.1 ± 17.6 mg/L) by decreasing carprofen absorption in the gastrointestinal tract.8 Elimination of substances that undergo enterohepatic recirculation (e.g., NSAIDs, theobromine, cholecalciferol, tetrahydrocannabinol) may be enhanced by repeated oral doses of activated charcoal.1,3

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November 2008

viously. Activated charcoal and a saline cathartic may be given, although [ethylene glycol] is not significantly adsorbed by charcoal.” I verified this information with the sources cited in the article.1,2 I also gathered information from the sixth edition of Ettinger’s Textbook of Veterinary Internal Medicine,3 which states to administer activated charcoal for recent exposure (≤2 hr). The recommendation we stated is conditional on the duration of exposure.

For metaldehyde, we wrote, “If the patient presents acutely, is alert, and does not have excessive muscle tremors or seizures, an emetic should be given, followed by activated charcoal and a cathartic.” Again, I verified this statement with the sources cited in the article4,5 as well as The 5-Minute Veterinary Consult

by Tilley,6 which recommends emetics or gastric lavage followed by administration of activated charcoal to prevent further absorption in animals with no clinical signs.

Julie Ann Luiz, DVM References 1. Osweiler GD. Common household products. In: Nieginski EA, ed. The National Veterinary Medical Series: CONTINUES ON PAGE 114

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Clinical Snapshot Answers and Explanations Case Presentation #1 SEE PAGE 104 FOR CASE PRESENTATION.

1. Scabies infestation. The organism

is a Sarcoptes egg. One mite or egg is diagnostic for scabies. Defi nitive evidence of a scabies infestation (eggs or mites) is not always found, even in “classic cases.” Most dogs with scabies are diagnosed based on response to treatment; therefore, if scabies is suspected, it should be treated accordingly.

2. Scabies mites can live for a short period of time off the host. The kennel facilities should be thoroughly cleaned with high-pressure water, scrubbed with detergent, and sprayed with an environmental parasiticidal agent. All dogs in contact with these Great Danes should be treated for scabies. Lime sulfur dips once weekly for 6 weeks or amitraz dips every 2 weeks for 6 weeks are effective topical therapies. Lime sulfur can be combined with ivermectin therapy. Ivermectin (200 μg/kg PO or SC) every 2 weeks for 6 weeks is also an effective treatment. I use a test dose of 100 μg/kg PO in all dogs. If there are no adverse effects consistent with ivermectin sensitiv-

A

ity (e.g., tremors, salivation) within 24 hours, I administer a full treatment dose of 200 μg/kg PO the next day.

Herding breeds of dogs, especially collies, are known to be sensitive to ivermectin. Thus, this drug is best avoided in collies.

Dogs sensitive to ivermectin can often tolerate milbemycin oxime at 3 mg/kg PO weekly for 3 to 6 weeks. Lime sulfur dips are also an effective therapy. Doramectin at 0.2 mg/kg SC or IM has also been reported to be effective. Finally, two applications of selamectin or fipronil at 30-day intervals may be effective. Selamectin is licensed for the treatment of scabies, and the manufacturer reported it to be effective in 70% of cases. Fipronil is not licensed for scabies treatment but has been found to be effective. It is important to remember that no treatment is 100% efficacious in all patients. If scabies is suspected and the patient does not respond, retreatment with a different therapy should be performed before scabies is ruled out.

B

3. Canine scabies is not considered con-

tagious to cats. However, Sarcoptes mites have been reported in a small number of cats with severe debilitation and in pruritic cats in England.

There may be some geographic variation with respect to contagion to cats. These cats do not need to be treated. True “feline scabies” is caused

by Notoedres cati, a contagious mange mite. In contrast to canine scabies mites, N. cati is easily found in large numbers on skin scrapings. Lesions occur on the head, feet, and perineum. This infestation can cause large amounts of crust; cats should be sedated, the haircoat clipped, and the cats bathed to remove the contaminated crusts before treatment. Because cats are extremely sensitive to parasiticidal agents, lime sulfur and ivermectin are the most commonly used treatments.

Affected cats, and all animals in contact with them, should be treated for at least 6 weeks.

Letters

Call for Papers Are you involved in research?

Veterinary Therapeutics: Research in Applied Veterinary Medicine® is a quarterly journal dedicated to rapid publication.

We invite the submission of clinical and laboratory research manuscripts in small animal, large animal, and comparative medicine, including pathophysiology, diagnosis, treatment, and prognosis. Prospective, retrospective, and corroborative studies are all welcome. Submitted articles are scheduled to be published 90 to 120 days after acceptance.

Contact Cheryl Hobbs, 800-426-9119, ext 52408, or email chobbs@vetlearn.com.

It’s not just therapeutics!

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Toxicology. Philadelphia: Williams and Wilkins; 1996:317-328.

2. Gaynor AR, Dhupa N. Acute ethylene glycol intoxication. Part II. Compend Contin Educ Pract Vet 1999;21(12):11241133.

3. Dorman DC, Dye JA. Chemical toxicities. In: Ettinger SJ, Feldman EC, eds.

Textbook of Veterinary Internal Medicine.

6th ed. St. Louis: Elsevier Saunders; 2005:257-258.

4. Richardson JA, Welch SL, GwaltneyBrant SM, et al. Metaldehyde toxicoses in dogs. Compend Contin Educ Pract Vet 2003;25(5):376-380.

5. Mull RL. Metaldehyde poisoning. In: Kirk RW, ed. Current Veterinary Therapy: Small Animal Practice VIII. London: WB Saunders; 1983:106-107.

6. Tilley LP, Smith FWK Jr. The 5-Minute Veterinary Consult: Canine and Feline.

2nd ed. Philadelphia: Lippincott Williams & Wilkins;2000:958-959.

Compendium: Continuing Education for Veterinarians® | March 2009 | CompendiumVet.com

Editor’s note: Thank you to the attentive readers who pointed out the difference between these articles and to the authors for their clarification. As in many aspects of veterinary medicine, different recommendations exist based on clinical experience and patient presentation versus laboratory chemistry, and different references reflect these variations. Awareness of both laboratory and clinical data is useful when determining the most appropriate treatment for an individual patient.

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Probiotic Therapy Improves Chronic Feline Diarrhea Christy Evans Cutting, DVM Companion Animal Clinic Roseburg, Oregon

Patient: Calliope, an 11-year-old domestic short-haired cat

Therapy Plan: After her surgery, I expected Calliope to have some loose stools, but when she presented with persistent diarrhea, I felt that her digestive system needed a little help to restore its normal microflora balance. I recommended that we try Purina Veterinary Diets® FortiFlora® Feline Nutritional Supplement. I started sprinkling FortiFlora on her food each day. FortiFlora was definitely what she needed. Within the first week, she started eating more and her diarrhea resolved.

Eating has always been a challenge for Calliope; she’s very particular and will become anorectic if she doesn’t like a particular food. She’s small to begin with (6 lb), so we’re constantly watchful for any weight loss. Because Calliope’s digestive system was so delicate after surgery, maintaining her appetite was a priority for us and her owner. In addition, Calliope had lost a significant amount of weight, so we offered her a variety of commercial foods to encourage her to eat.

Outcome: Calliope really didn’t seem “better” until we started FortiFlora. Until recently, her owner was giving her the nutritional supplement daily because if she missed one dose, the diarrhea would return. After 2 years, her owner was able to discontinue FortiFlora, and Calliope is now eating well and doing great without any gastrointestinal problems!

This information has not been peer reviewed and does not necessarily reflect the opinions of, nor constitute or imply endorsement or recommendation by, the Publisher or Editorial Board. The Publisher is not responsible for any data, opinions, or statements provided herein.

©Jeannine Cook

History: In January 2004, Calliope presented with constipation. We administered two enemas and prescribed 1 mL lactulose once every 12 to 24 hours. She did reasonably well on lactulose for approximately 1 year, but the constipation returned. At this point, we increased the dose of lactulose to 1 mL every 8 hours, which worked until January 2006.

This time, the constipation didn’t respond to enemas, so we sedated Calliope for manual removal of the impacted feces. Unfortunately, she didn’t tolerate sedation well.

She became hypothermic and almost comatose; intensive care, including intravenous fluids with corticosteroids, was needed to help pull her through. She slowly improved over the next 3 days and began eating on the fourth day.

She was sent home but returned the next day with diarrhea and vomiting. I referred her owner to the nearest specialist for more involved diagnostics and treatment. Luckily they obliged—Calliope was diagnosed with an abnormal colon that required a partial colectomy 2 days later.

Calliope has had no more problems with constipation, but she developed diarrhea for 6 months following surgery.

Calliope Veterinarian’s Comments I have been recommending Purina Veterinary Diets ® FortiFlora ® as a nutritional supplement for more than 2 years. I like FortiFlora for several reasons: It’s convenient to dispense and administer, it’s easy on the GI tract, cats love the taste, and it works! Calliope’s owner really feels that FortiFlora made the difference for her cat.

I commonly use the nutritional supplement in dogs and cats that develop mild diarrhea when receiving antibiotics. It’s nice to have something to offer owners when they call with this problem, without having to change antibiotics or bring the pet back in for a recheck. I also commonly use FortiFlora for pets with stress diarrhea—It seems to work very well for these cases.

I recommend that my veterinary colleagues try FortiFlora. It’s easy to administer; you just sprinkle the nutritional supplement on the pet’s food. It works fast and is so simple and effective!

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Understanding

Behavior

Feline Hyperesthesia Syndrome*

About This Column

❯❯ John Ciribassi, DVM, DACVB

Behavior problems are a significant cause of death (euthanasia) in companion animals. While most veterinary practices are necessarily geared toward the medical aspect of care, there are many opportunities to bring behavior awareness into the clinic for the benefit of the pet, the owner, and ourselves.

This column acknowledges the importance of behavior as part of veterinary medicine and speaks practically about using it effectively in daily practice.

Chicagoland Veterinary Behavior Consultants Carol Stream, Illinois

F

eline hyperesthesia syndrome (FHS) is known by several names, including rolling skin disease, neurodermatitis, neuritis, psychomotor epilepsy, and pruritic dermatitis of Siamese.1,2 As evidenced by these names and by the use of the term syndrome, FHS is not characterized as having a single etiology. In fact, it is often a diagnosis of exclusion. The differential diagnosis for FHS includes diseases related to the fields of dermatology, neurology, and behavior. Only after conditions relating to skin and the nervous system have been ruled out can this condition be labeled a behavior disorder.

Signalment FHS can occur in cats of any age, but it is commonly seen in cats aged 1 to 5 years. Males and females are equally affected. While all breeds can be affected, Siamese, Burmese, Persian, and Abyssinian cats are more commonly afflicted.3

QuickNotes FHS can occur in cats of any age, but it is commonly seen in cats aged 1 to 5 years.

Diagnosis *Adapted with permission from John Ciribassi, DVM, and the Veterinary Information Network (VIN).

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CompendiumVet.com | March 2009

The differential diagnosis for FHS can be categorized by the type of clinical signs displayed:

©2009 Kelpfish/Shutterstock.com

Clinical Signs As indicated by the name rolling skin disease, affected cats often show rippling or rolling skin along the lumbar spine. Palpation of the lumbar musculature may elicit signs of pain. Mydriasis is common during bouts of FHS. Affected cats commonly stare at their tail, then attack the tail and/or flanks. Biting of the tail base, forelegs, and paws is common. These cats often run wildly around the home, vocalizing at the same time. Normally calm cats may display aggression toward people or other cats in the household, while aggressive cats may display increased affection. The behavior may be induced by petting or stroking the cat’s fur and most commonly occurs in the morning or later in the evening.2

Raising the level of care “AAHA is continually looking for ways to help

member practices run better. AAHA endorses Vetstreet because it offers clinics an important client outreach tool. The Vetstreet Pet Portal® service allows us to better connect with and educate our clients, increase compliance and, most importantly, raise the level of health care for our patients.

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Easy to set up and easy to use, Vetstreet® is a powerful practice communication and management tool that keeps you in touch with your clients via Pet Portals. To discover how Vetstreet can help you increase client satisfaction, build compliance, and enhance your bottom line, visit Vetstreet.com, call toll-free 888-799-8387, or email info@vetstreet.com.

Vetstreet and Pet Portal are registered trademarks of VetInsite.com, Inc.

Understanding

Behavior

QuickNotes Successful therapy is based on reasonable owner expectations and the ability to monitor the degree of improvement.

Dermatologic: Flea allergy dermatitis, food allergy, atopy, infectious dermatitis Neurologic: Epilepsy, brain tumors, spinal disease (disk disease, neoplasia, infectious myelitis) Musculoskeletal: Myositis, myopathy Behavioral: Compulsive disorder, displacement behavior A minimum database to aid in diagnosing FHS should include a physical examination, neurologic examination, complete blood count, serum chemistry profile (especially hepatic and renal function), urinalysis, and spinal radiography. Depending on these results, further diagnostics might include skin scraping, fungal culture, skin and/or muscle biopsy, spinal or cranial imaging (computed tomography or magnetic resonance imaging), electromyography, food trials, and pharmaceutical trials (flea control, corticosteroids, antiseizure medication). The decision of which tests to run and in what order depends on the patience and financial situation of the owner and the severity of the clinical signs.

While running the gamut of tests is ideal, it may be more practical to use pharmaceutical trials once the baseline database has been collected. I typically suggest a trial of flea control medication and, if there is no change, treatment with corticosteroids at antiinflammatory doses. If the patient does not respond to steroid treatment, treatment with an antiseizure medication is indicated. Phenobarbital is my initial antiseizure drug of choice; some practitioners also use gabapentin.

If none of the above approaches results in an improvement in the cat’s condition, then a presumed diagnosis of behavioral FHS can be made.

Pathophysiology

unrelated, behavior such as grooming. If this conflicting situation persists over a prolonged period, the cat may engage in the displacement behavior even when the competing motivations are no longer present. This is then defined as a compulsive behavior.

The environmental factors that trigger compulsive behaviors exert their influence by stimulating the hypothalamus and the limbic system, which in turn activate motor activity through the basal ganglia. Three types of neurotransmitters are reported to be involved: Dopamine. Increased dopamine levels can result in increased frequency of compulsive behaviors.

Opiates. One theory is that when animals engage in compulsive behaviors, levels of opiates in the brain are elevated, and the pleasurable effects that opiates promote reinforce the behaviors. Another theory is that opiates initiate stereotypic behavior.

This theory is based on the observation that administration of opioids enhances the display of amphetamine-induced stereotypic behaviors, but these behaviors are blocked when narcotic antagonists (such as naloxone) are administered.4 Serotonin. Serotonin is produced in the dorsal raphe nucleus, and its influence on the basal ganglia and frontal cortex affects behaviors such as compulsive disorders. Higher levels of serotonin reduce the incidence of compulsive disorders, which is the rationale for the use of selective serotonin reuptake inhibitors (SSRIs) to treat these disorders.

Treatment Successful therapy is based on reasonable owner expectations and the ability to monitor the degree of improvement. This can be accomplished by recording the frequency and severity of signs of FHS during the treatment period.

©2009 Dr. Margorius/Shutterstock.com

FHS is commonly considered to be a compulsive disorder resulting in self-injurious behavior. One proposed trigger of FHS is displacement behavior. Displacement behav- Behavior Modification ior occurs as an alternative to two other con- As with many behavior problems in companflicting behaviors. An example might be a cat ion animals, the treatment of FHS combines that wants to eat but is being prevented from behavior modification protocols and the use doing so by an aggressive cat in the house- of psychoactive pharmaceuticals. Behaviorally, hold. The competing motivations, hunger and the goal is to create a stable and consistent fear, cause the affected cat to want to simulta- environment for the cat. This can be accomneously perform the conflicting behaviors of plished in the following ways: Institute a regular feeding schedule to proeating and escaping. As a consequence, the vide a more predictable source of food. cat might perform a species-appropriate, but

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So you think you know everything about SevoFlo®(sevoflurane)…

...a few dollars more* gives you all that SevoFlo has to offer.

• SevoFlo is only a few dollars more per procedure and with your normal markups can increase your potential profits.

• SevoFlo can provide the opportunity to differentiate your talents and practice from others.

• SevoFlo doesn’t irritate airways1 and is less of a respiratory depressant than isoflurane2.

• SevoFlo has low blood:gas solubility and a greater range of vaporizer settings to give veterinarians rapid, precise control over the depth of anesthesia.

For only a few dollars more* you get all of the benefits of SevoFlo. Speak to your sales representative, contact Abbott Animal Health at 888-299-7416 or visit us at www.abbottanimalhealth.com today.

Important Information: How Supplied: SevoFlo is packaged in amber colored bottles containing 250 mL sevoflurane. Indications: SevoFlo is indicated for induction and maintenance of general anesthesia in dogs. Warnings, Precautions, and Contraindications: Like other inhalation anesthetics, sevoflurane is a profound respiratory depressant. Respiration must be monitored closely in the dog and supported when necessary with supplemental oxygen and/or assisted ventilation. Due to sevoflurane’s low solubility in blood, increasing concentration may result in rapid hemodynamic changes compared to other volatile anesthetics. SevoFlo is contraindicated in dogs with a known sensitivity to sevoflurane or other halogenated agents. Adverse Reactions: The most frequently reported adverse reactions during maintenance anesthesia were hypotension, followed by tachypnea, muscle tenseness, excitation, apnea, muscle fasciculations and emesis. See package insert for full prescribing information.

SEVO-210 February 2009 ©2009 Abbott Laboratories

1

T Mutoh, A Kanamura, H Suzuki, H Tsubone, R Nishimura, N Sasaki. AJVR 2001:62:311-319

2

DS Galloway JCH Ko, HF Reaugh, RE Mandsager, ME Payton, T Inoue, E Portillo. JAVMA (2004) Vol 255, No 5, 700-704

*

Per procedure.

See Page 120 for Product Information Summary

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SevoFlo®

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5458

(sevoflurane) Inhalation Anesthetic For Use in Dogs Caution: Federal law restricts this drug to use by or on the order of a licensed veterinarian.

DESCRIPTION: SevoFlo (sevoflurane), a volatile liquid, is a halogenated general inhalation anesthetic drug. Its chemical name is fluoromethyl 2,2,2trifluoro-l- (trifluoromethyl) ethyl ether, and its structural formula is:

Sevoflurane Physical Constants are: Molecular weight 200.05 Boiling point at 760 mm Hg 58.6°C Specific gravity at 20°C 1.520-1.525 g/mL Vapor pressure in mm Hg at 20°C 157 at 25°C 197 at 36°C 317 Distribution Partition Coefficients at 37°C: Blood/Gas 0.63-0.69 Water/Gas 0.36 Olive Oil/Gas 47-54 Brain/Gas 1.15 Mean Component/Gas Partition Coefficients at 25°C for Polymers Used Commonly in Medical Applications: Conductive rubber 14.0 Butyl rubber 7.7 Polyvinyl chloride 17.4 Polyethylene 1.3 Sevoflurane is nonflammable and nonexplosive as defined by the requirements of International Electrotechnical Commission 601-2-13. Sevoflurane is a clear, colorless, stable liquid containing no additives or chemical stabilizers.

Sevoflurane is nonpungent. It is miscible with ethanol, ether, chloroform and petroleum benzene, and it is slightly soluble in water. Sevoflurane is stable when stored under normal room lighting condition according to instructions.

INDICATIONS: SevoFlo is indicated for induction and maintenance of general anesthesia in dogs.

DOSAGE AND ADMINISTRATION: Inspired Concentration: The delivered concentration of SevoFlo should be known. Since the depth of anesthesia may be altered easily and rapidly, only vaporizers producing predictable percentage concentrations of sevoflurane should be used. Sevoflurane should be vaporized using a precision vaporizer specifically calibrated for sevoflurane. Sevoflurane contains no stabilizer. Nothing in the drug product alters calibration or operation of these vaporizers. The administration of general anesthesia must be individualized based on the patient’s response. WHEN USING SEVOFLURANE, PATIENTS SHOULD BE CONTINUOUSLY MONITORED AND FACILITIES FOR MAINTENANCE OF PATENT AIRWAY, ARTIFICIAL VENTILATION, AND OXYGEN SUPPLEMENTATION MUST BE IMMEDIATELY AVAILABLE. Replacement of Desiccated CO2 Absorbents: When a clinician suspects that the CO2 absorbent may be desiccated, it should be replaced. An exothermic reaction occurs when sevoflurane is exposed to CO2 absorbents. This reaction is increased when the CO2 absorbent becomes desiccated (see PRECAUTIONS).

Premedication: No specific premedication is either indicated or contraindicated with sevoflurane. The necessity for and choice of premedication is left to the discretion of the veterinarian. Preanesthetic doses for premedicants may be lower than the label directions for their use as a single medication.1 Induction: For mask induction using sevoflurane alone, inspired concentrations up to 7% sevoflurane with oxygen are employed to induce surgical anesthesia in the healthy dog. These concentrations can be expected to produce surgical anesthesia in 3 to 14 minutes. Due to the rapid and dose dependent changes in anesthetic depth, care should be taken to prevent overdosing.

Respiration must be monitored closely in the dog and supported when necessary with supplemental oxygen and/or assisted ventilation.

Maintenance: SevoFlo may be used for maintenance anesthesia following mask induction using sevoflurane or following injectable induction agents. The concentration of vapor necessary to maintain anesthesia is much less than that required to induce it. Surgical levels of anesthesia in the healthy dog may be maintained with inhaled concentrations of 3.7-4.0% sevoflurane in oxygen in the absence of premedication and 3.3-3.6% in the presence of premedication. The use of injectable induction agents without premedication has little effect on the concentrations of sevoflurane required for maintenance. Anesthetic regimens that include opioid, alpha2-agonist, benzodiazepine or phenothiazine premedication will allow the use of lower sevoflurane maintenance concentrations.

CONTRAINDICATIONS: SevoFlo is contraindicated in dogs with a known sensitivity to sevoflurane or other halogenated agents.

WARNINGS: Sevoflurane is a profound respiratory depressant. DUE TO THE RAPID AND DOSE DEPENDENT CHANGES IN ANESTHETIC DEPTH, RESPIRATION MUST BE MONITORED CLOSELY IN THE DOG AND SUPPORTED WHEN NECESSARY WITH SUPPLEMENTAL OXYGEN AND/OR ASSISTED VENTILATION. In cases of severe cardiopulmonary depression, discontinue drug administration, ensure the existence of a patent airway and initiate assisted or controlled ventilation with pure oxygen. Cardiovascular depression should be treated with plasma expanders, pressor agents, antiarrhythmic agents or other techniques as appropriate for the observed abnormality. Due to sevoflurane’s low solubility in blood, increasing the concentration may result in rapid changes in anesthetic depth and hemodynamic changes (dose dependent decreases in respiratory rate and blood pressure) compared to other volatile anesthetics. Excessive decreases in blood pressure or respiratory depression may be corrected by decreasing or discontinuing the inspired concentration of sevoflurane.

Potassium hydroxide containing CO2 absorbents (e.g. BARALYME®) are not recommended for use with sevoflurane.

ADVERSE REACTIONS: The most frequently reported adverse reactions during maintenance anesthesia were hypotension, followed by tachypnea, muscle tenseness, excitation, apnea, muscle fasciculations and emesis.

Infrequent adverse reactions include paddling, retching, salivation, cyanosis, premature ventricular contractions and excessive cardiopulmonary depression.

Transient elevations in liver function tests and white blood cell count may occur with sevoflurane, as with the use of other halogenated anesthetic agents.

PRECAUTIONS: Halogenated volatile anesthetics can react with desiccated carbon dioxide (CO2) absorbents to produce carbon monoxide (CO) that may result in elevated carboxyhemoglobin levels in some patients. To prevent this reaction, sevoflurane should not be passed through desiccated soda lime or barium hydroxide lime.

Replacement of Desiccated CO2 Absorbents: When a clinician suspects that the CO2 absorbent may be desiccated, it should be replaced before administration of sevoflurane. The exothermic reaction that occurs with sevoflurane and CO2 absorbents is increased when the CO2 absorbent becomes desiccated, such as after an extended period of dry gas flow through the CO2 absorbent canisters. Extremely rare cases of spontaneous fire in the respiratory circuit of the anesthesia machine have been reported during sevoflurane use in conjunction with the use of a desiccated CO2 absorbent, specifically those containing potassium hydroxide (e.g. BARALYME).

Potassium hydroxide containing CO2 absorbents are not recommended for use with sevoflurane. An unusually delayed rise in the inspired gas concentration (decreased delivery) of sevoflurane compared with the vaporizer setting may indicate excessive heating of the CO2 absorbent canister and chemical breakdown of sevoflurane. The color indicator of most CO2 absorbent may not change upon desiccation. Therefore, the lack of significant color change should not be taken as an assurance of adequate hydration. CO2 absorbents should be replaced routinely regardless of the state of the color indicator.

The use of some anesthetic regimens that include sevoflurane may result in bradycardia that is reversible with anticholinergics. Studies using sevoflurane anesthetic regimens that included atropine or glycopyrrolate as premedicants showed these anticholinergics to be compatible with sevoflurane in dogs.

During the induction and maintenance of anesthesia, increasing the concentration of sevoflurane produces dose dependent decreases in blood pressure and respiratory rate. Due to sevoflurane’s low solubility in blood, these changes may occur more rapidly than with other volatile anesthetics.

Excessive decreases in blood pressure or respiratory depression may be related to depth of anesthesia and may be corrected by decreasing the inspired concentration of sevoflurane. RESPIRATION MUST BE MONITORED CLOSELY IN THE DOG AND SUPPORTED WHEN NECESSARY WITH SUPPLEMENTAL OXYGEN AND/OR ASSISTED VENTILATION. The low solubility of sevoflurane also facilitates rapid elimination by the lungs.

The use of sevoflurane in humans increases both the intensity and duration of neuromuscular blockade induced by nondepolarizing muscle relaxants. The use of sevoflurane with nondepolarizing muscle relaxants has not been evaluated in dogs.

Compromised or debilitated dogs: Doses may need adjustment for geriatric or debilitated dogs. Because clinical experience in administering sevoflurane to dogs with renal, hepatic and cardiovascular insufficiency is limited, its safety in these dogs has not been established.

Breeding dogs: The safety of sevoflurane in dogs used for breeding purposes, during pregnancy, or in lactating bitches, has not been evaluated.

Neonates: The safety of sevoflurane in young dogs (less than 12 weeks of age) has not been evaluated.

HUMAN SAFETY: Not for human use. Keep out of reach of children.

Operating rooms and animal recovery areas should be provided with adequate ventilation to prevent the accumulation of anesthetic vapors.

There is no specific work exposure limit established for sevoflurane. However, the National Institute for Occupational Safety and Health has recommended an 8 hour time-weighted average limit of 2 ppm for halogenated anesthetic agents in general. Direct exposure to eyes may result in mild irritation. If eye exposure occurs, flush with plenty of water for 15 minutes. Seek medical attention if irritation persists. Symptoms of human overexposure (inhalation) to sevoflurane vapors include respiratory depression, hypotension, bradycardia, shivering, nausea and headache. If these symptoms occur, remove the individual from the source of exposure and seek medical attention. The material safety data sheet (MSDS) contains more detailed occupational safety information. For customer service, adverse effects reporting, and/or a copy of the MSDS, call (888) 299-7416.

CLINICAL PHARMACOLOGY: Sevoflurane is an inhalational anesthetic agent for induction and maintenance of general anesthesia. The Minimum Alveolar Concentration (MAC) of sevoflurane as determined in 18 dogs is 2.36%.2 MAC is defined as that alveolar concentration at which 50% of healthy patients fail to respond to noxious stimuli. Multiples of MAC are used as a guide for surgical levels of anesthesia, which are typically 1.3 to 1.5 times the MAC value. Because of the low solubility of sevoflurane in blood (blood/gas partition coefficient at 37°C = 0.63-0.69), a minimal amount of sevoflurane is required to be dissolved in the blood before the alveolar partial pressure is in equilibrium with the arterial partial pressure. During sevoflurane induction, there is a rapid increase in alveolar concentration toward the inspired concentration. Sevoflurane produces only modest increases in cerebral blood flow and metabolic rate, and has little or no ability to potentiate seizures.3 Sevoflurane has a variable effect on heart rate, producing increases or decreases depending on experimental conditions.4,5 Sevoflurane produces dose-dependent decreases in mean arterial pressure, cardiac output and myocardial contraction.6 Among inhalation anesthetics, sevoflurane has low arrhythmogenic potential.7 Sevoflurane is chemically stable. No discernible degradation occurs in the presence of strong acids or heat. Sevoflurane reacts through direct contact with CO2 absorbents (soda lime and barium hydroxide lime) producing pentafluoroisopropenyl fluoromethyl ether (PIFE, C4H2F6O), also known as Compound A, and trace amounts of pentafluoromethoxy isopropyl fluoromethyl ether (PMFE, C5H6F6O), also known as Compound B. Compound A: The production of degradants in the anesthesia circuit results from the extraction of the acidic proton in the presence of a strong base (potassium hydroxide and/or NaOH) forming an alkene (Compound A) from sevoflurane.

Compound A is produced when sevoflurane interacts with soda lime or barium hydroxide lime. Reaction with barium hydroxide lime results in a greater production of Compound A than does reaction with soda lime. Its concentration in a circle absorber system increases with increasing sevoflurane concentrations and with decreasing fresh gas flow rates. Sevoflurane degradation in soda lime has been shown to increase with temperature. Since the reaction of carbon dioxide with absorbents is exothermic, this temperature increase will be determined by the quantities of CO2 absorbed, which in turn will depend on fresh gas flow in the anesthetic circle system, metabolic status of the patient and ventilation. Although Compound A is a dose-dependent nephrotoxin in rats, the mechanism of this renal toxicity is unknown. Two spontaneously breathing dogs under sevoflurane anesthesia showed increases in concentrations of Compound A as the oxygen flow rate was

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decreased at hourly intervals, from 500 mL/min (36 and 18 ppm Compound A) to 250 mL/min (43 and 31 ppm) to 50 mL/min (61 and 48 ppm).8 Fluoride ion metabolite: Sevoflurane is metabolized to hexafluoroisopropanol (HFIP) with release of inorganic fluoride and CO2. Fluoride ion concentrations are influenced by the duration of anesthesia and the concentration of sevoflurane. Once formed, HFIP is rapidly conjugated with glucuronic acid and eliminated as a urinary metabolite. No other metabolic pathways for sevoflurane have been identified. In humans, the fluoride ion half-life was prolonged in patients with renal impairment, but human clinical trials contained no reports of toxicity associated with elevated fluoride ion levels. In a study in which 4 dogs were exposed to 4% sevoflurane for 3 hours, maximum serum fluoride concentrations of 17.0-27.0 mcmole/L were observed after 3 hours of anesthesia.

Serum fluoride fell quickly after anesthesia ended, and had returned to baseline by 24 hours post-anesthesia. In a safety study, eight healthy dogs were exposed to sevoflurane for 3 hours/day, 5 days/week for 2 weeks (total 30 hours exposure) at a flow rate of 500 mL/min in a semi-closed, rebreathing system with soda lime. Renal toxicity was not observed in the study evaluation of clinical signs, hematology, serum chemistry, urinalysis, or gross or microscopic pathology.

DRUG INTERACTIONS: In the clinical trial, sevoflurane was used safely in dogs that received frequently used veterinary products including steroids and heartworm and flea preventative products.

Intravenous Anesthetics: Sevoflurane administration is compatible with barbiturates, propofol and other commonly used intravenous anesthetics. Benzodiazepines and Opioids: Benzodiazepines and opioids would be expected to decrease the MAC of sevoflurane in the same manner as other inhalational anesthetics. Sevoflurane is compatible with benzodiazepines and opioids as commonly used in surgical practice.

Phenothiazines and Alpha2-Agonists: Sevoflurane is compatible with phenothiazines and alpha2- agonists as commonly used in surgical practice.

In a laboratory study, the use of the acepromazine/oxymorphone/ thiopental/sevoflurane anesthetic regimen resulted in prolonged recoveries in eight (of 8) dogs compared to recoveries from sevoflurane alone.

CLINICAL EFFECTIVENESS: The effectiveness of sevoflurane was investigated in a clinical study involving 196 dogs.

Thirty dogs were mask-induced with sevoflurane using anesthetic regimens that included various premedicants. During the clinical study, one hundred sixty-six dogs received sevoflurane maintenance anesthesia as part of several anesthetic regimens that used injectable induction agents and various premedicants. The duration of anesthesia and the choice of anesthetic regimens were dependent upon the procedures that were performed. Duration of anesthesia ranged from 16 to 424 minutes among the individual dogs. Sevoflurane vaporizer concentrations during the first 30 minutes of maintenance anesthesia were similar among the various anesthetic regimens. The quality of maintenance anesthesia was considered good or excellent in 169 out of 196 dogs. The table shows the average vaporizer concentrations and oxygen flow rates during the first 30 minutes for all sevoflurane maintenance anesthesia regimens: Average Vaporizer Concentrations among Anesthetic Regimens

Average Vaporizer Concentrations among Individual Dogs

3.31 - 3.63%

1.6 - 5.1%

Average Oxygen Flow Rates among Anesthetic Regimens 0.97 - 1.31 L/minute

Average Oxygen Flow Rates among Individual Dogs 0.5 - 3.0 L/minute

During the clinical trial, when a barbiturate was used for induction, the times to extubation, sternal recumbency and standing recovery were longer for dogs that received anesthetic regimens containing two preanesthetics compared to regimens containing one preanesthetic. Recovery times were shorter when anesthetic regimens used sevoflurane or propofol for induction. The quality of recovery was considered good or excellent in 184 out of 196 dogs. Anesthetic regimen drug dosages, physiological responses, and the quality of induction, maintenance and recovery were comparable between 10 sighthounds and other breeds evaluated in the study. During the clinical study there was no indication of prolonged recovery times in the sighthounds.

HOW SUPPLIED: SevoFlo (sevoflurane) is packaged in amber colored bottles containing 250 mL sevoflurane, List 5458.

STORAGE CONDITIONS: Store at controlled room temperature 15°-30°C (59°-86°F).

REFERENCES: 1. Plumb, D.C. ed., Veterinary Drug Handbook, Second Edition, University of Iowa Press, Ames, IA: p. 424 (1995).

2. Kazama, T. and Ikeda, K., Comparison of MAC and the rate of rise of alveolar concentration of sevoflurane with halothane and isoflurane in the dog. Anesthesiology.

68: 435-437 (1988).

3. Scheller, M.S., Nakakimura, K., Fleischer, J.E. and Zornow, M.H., Cerebral effects of sevoflurane in the dog: Comparison with isoflurane and enflurane. Brit. J. Anesthesia 65: 388-392 (1990).

4. Frink, E.J., Morgan, S.E., Coetzee, A., Conzen, P.F. and Brown, B.R., Effects of sevoflurane, halothane, enflurane and isoflurane on hepatic blood flow and oxygenation in chronically instrumented greyhound dogs. Anesthesiology 76: 85-90 (1992).

5. Kazama, T. and Ikeda, K., The comparative cardiovascular effects of sevoflurane with halothane and isoflurane. J. Anesthesiology 2: 63-8 (1988).

6. Bernard, J. M., Wouters, P.F., Doursout, M.F., Florence, B., Chelly, J.E. and Merin, R.G., Effects of sevoflurane on cardiac and coronary dynamics in chronically instrumented dogs. Anesthesiology 72: 659-662 (1990).

7. Hayaski, Y., Sumikawa, K., Tashiro, C., Yamatodani, A. and Yoshiya, I., Arrhythmogenic threshold of epinephrine during sevoflurane, enflurane and isoflurane anesthesia in dogs. Anesthesiology 69: 145-147 (1988).

8. Muir, W.W. and Gadawski, J., Cardiorespiratory effects of low-flow and closed circuit inhalation anesthesia, using sevoflurane delivered with an in-circuit vaporizer and concentrations of compound A. Amer. J. Vet. Res. 59 (5): 603-608 (1998).

NADA 141-103, Approved by FDA SevoFlo® is a registered trademark of Abbott Laboratories.

Manufactured by Abbott Laboratories, North Chicago, IL 60064, USA Product of Japan Under license from Maruishi Pharmaceutical Co., LTD 2-3-5, Fushimi-Machi, Chuo-Ku, Osaka, Japan For customer service call (888) 299-7416. ©Abbott 8/2006 Taken from Commodity Number 03-5474/R6, SevoFlo, sevoflurane, package insert, January 11, 2007

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Understanding

Behavior

QuickNotes FHS behaviors should not be punished because punishment will increase the cat’s conflict and stress, resulting in a likely increase in the problem behaviors.

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©2009 Vasiliy Koval/Shutterstock.com

Maintain consistency in interactions with the administration of the medication. If the patient cat. When managing dogs with a compulsive is receiving combination therapy (an SSRI or disorder, one common recommendation is TCA with a benzodiazepine), the medications for the owners to use a command–response– should be weaned one at a time to determine reward technique for all interactions. For which drug is responsible if signs return as the example, the owner asks the dog to sit and, dose is reduced. after the dog obeys, gives it a treat. The same Selective Serotonin Reuptake Inhibitors technique can be used with cats.

Provide regular play sessions using target- The following dosages are recommended for type toys (e.g., feather toys). cats with FHS6: Anticipate situations that trigger the behavior.

Fluoxetine: 0.5 to 2.0 mg/kg PO q24h When the behavior is likely to occur, redirect Paroxetine: 0.5 to 1.0 mg/kg PO q12–24h the cat’s activity to more appropriate behaviors, such as training exercises or play.3,5 The adverse effects of SSRIs include sedaFHS behaviors should not be punished tion, anorexia, irritability, vomiting, and diarbecause punishment will increase the cat’s con- rhea. In addition, SSRIs inhibit the function of flict and stress, resulting in a likely increase in the liver cytochrome P450 enzymes CYP2C9, the problem behaviors.

CYP2D6, CYP2C19, and CYP3A4. As a consequence, care should be taken when prescribPharmaceutical Intervention ing concurrent medications that rely on these There are no US Food and Drug Administration– enzymes for their metabolism (e.g., phenoapproved medications for treating FHS or barbital, carbamazepine, benzodiazepines, any other compulsive disorder in pets. Con- TCAs). SSRIs should not be used in combinasequently, owners should be informed of the tion with each other or with other drugs that potential risks as well as the possible benefits increase serotonin levels, such as monoamof the use of behavior medications. It is always ine oxidase inhibitors (e.g., selegiline), other wise to conduct appropriate laboratory testing SSRIs (e.g., paroxetine, sertraline), or TCAs to confirm normal hepatic and renal function (e.g., amitriptyline, imipramine, doxepin). before prescribing these medications, which are metabolized and eliminated by the liver Tricyclic Antidepressants and kidneys. It is also helpful to repeat test- Of the TCAs, clomipramine (0.5 to 1.0 mg/kg ing approximately 4 weeks after instituting PO q24h)7 can be used to treat FHS. Adverse therapy to evaluate the medication’s effect on effects associated with this drug include sedation, anticholinergic effects, potentiation organ (particularly hepatic) function.

The three main classes of medications used of arrhythmias in predisposed patients, and to treat FHS are SSRIs, tricyclic antidepressants lowering of the seizure threshold in patients (TCAs), and benzodiazepines. When using any with seizure disorders. of these medications in cats, it is best to begin at the lower end of the dose range, then titrate Benzodiazepines upward as needed to achieve the desired The following dosages 8 are recomresponse. This approach minimizes the poten- mended for cats with FHS. These tial for serious side effects such as prolonged benzodiazepines are recommended in cats because they do not have active anorexia or excessive sedation.

Once the frequency of the behavior metabolites. Diazepam has been implireaches an acceptable level, treatment should cated in cases of hepatic necrosis in cats.

Lorazepam: 0.125 to 0.50 mg PO q8–24h be maintained for 4 to 6 months. The dose Oxazepam: 0.20 to 0.50 mg/kg PO q12–24h can then be gradually reduced (25% reduction every 1 to 2 weeks) until the patient has been weaned off the drug. If the behavior recurs The potential adverse effects of these drugs or increases in frequency during the weaning include sedation, ataxia, and temperament process, the previously effective dose should changes. Combination therapy with an SSRI or be reinstituted. Another reduction may be a TCA is acceptable with either of these drugs attempted after another 4 to 6 months of ther- if no agent alone provides sufficient response.

CONTINUES ON PAGE 132 apy; however, some patients require lifelong

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3 CE CREDITS

CE Article 1

Vomiting ❯❯ Héctor J. Encarnación, DVM Gulf Coast Veterinary Specialists Houston, Texas

❯❯ Joshua Parra, DVM Florida Veterinary Referral Center and 24-Hour Emergency and Critical Care Hospital Estero, Florida

❯❯ Erick Mears, DVM, DACVIM Valerie Sadler, DVM, DACVR Florida Veterinary Specialists and Cancer Treatment Center Tampa, Florida

At a Glance The Vomiting Reflex Page 122

Antiemetics Page 124

Vomiting Reflex Components, Receptors, and Controlling Neurotransmitters and Medications Page 125

Most Common Antiemetics Used in Small Animal Medicine Page 127

Treatment of Common Vomiting Conditions Page 128

Most Common Causes of Vomiting in Dogs and Cats Page 129

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Abstract: Vomiting is the forceful expulsion of stomach contents through the mouth, caused by humoral stimulation of the chemoreceptor trigger zone (CRTZ) or neural stimulation of the emetic center. The CRTZ is activated and controlled by neurotransmitter manipulation at the receptor level. Clinical signs preceding vomiting may include ptyalism, tachycardia, depression, hiding, and yawning. Gastritis, gastrointestinal ulceration, pancreatitis, motion sickness, uremia, chemotherapy, and drug administration are common initiating causes of vomiting. This article reviews the anatomic and physiologic aspects of the vomiting reflex and its neurotransmitters, associated receptors, and rational management.

E

mesis, or vomiting, is one of the most common reasons dogs and cats present for medical evaluation.1 Vomiting is often associated with mild, self-limiting diseases that resolve with minimal diagnostic tests and therapy.

However, it can be related to debilitating conditions that have life-threatening consequences. The history obtained from the client should be as detailed as possible because historical details are often helpful in selecting the appropriate treatment and diagnostic plan. Questions to ask during the history should include onset of vomiting, duration of clinical signs, type and frequency of vomiting, relation to food ingestion, characteristics of the vomited contents, diet history, and environment.

Questions about known medical conditions and current therapies are also pertinent because these factors may play an active role in the inciting cause.

The Vomiting Reflex Pathophysiology Vomiting is a reflex act that is mediated neurologically by the activation of the bilateral nucleus tractus solitarii, or emetic center, situated in the parvicellular reticular formation in the lateral region of the medulla oblongata. This is the area that initiates, controls, regulates, and organizes the vomiting reflex.2–5 Vomiting can be triggered by both neural and humoral pathways.2 The neural pathway comprises six fundamental

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components. The emetic center (1)2,6–12 receives input from (2) the gastrointestinal tract (afferent neurons),2,7–11,13 (3) the higher centers of the brain,2,7–9,13 (4) the vestibular apparatus,2,6–13 and (5) the CRTZ.2,6–13 Finally, to coordinate the vomiting reflex, the vomiting center sends signals through (6) the efferent motor neurons.7,8,10 The vagal and sympathetic afferent neurons originate from the gastrointestinal tract, particularly the duodenum, as well as other areas, including the urinary and reproductive system, liver, pancreas, peritoneum, and cardiac vessels. Stimulation of these neurons initiates the impulse that travels directly to the emetic center. The higher centers of the brain, including the cerebral cortex and the limbic system, can trigger emesis through three mechanisms: direct stimulation of the vomiting center by inflammatory diseases, hydrocephalus, or neoplasia; psychogenic stimulation caused by fear, stress, excitement, or pain; and traumatic stimulation related to head injuries and increased intracranial pressure.7,9 The CRTZ is a bilateral set of centers in the brainstem, located on the floor of the fourth ventricle. It possesses free nerve endings that maintain direct contact with the cerebrospinal fluid via ependymal pores or the sheath surrounding fenestrated capillaries.9,14 These free nerve endings are activated by the vestibular system or through the humoral pathway by conditions affecting the blood or cerebrospinal fluid (e.g., drug administration, infection, osmolar

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D08676n

FREE CE Vomiting

and acid–base disorders, electrolyte derangements, metabolic diseases).15 Finally, to initiate the vomiting reflex, efferent motor signals must be transmitted to the upper gastrointestinal tract through the sensory aspect of cranial nerves V, VII, IX, X, and XII and to the diaphragm and abdominal muscles via the spinal nerves.8

Anatomy

negative intrathoracic pressure and positive intraabdominal pressure, facilitating the movement of gastric contents into the esophagus. Before expulsion, the respiratory center is inhibited and the nasopharynx and glottis close to prevent pulmonary aspiration and nasal regurgitation of the gastric contents. The third and last phase of vomiting is the expulsion of stomach contents through the mouth.

The act of vomiting is composed of three phases: nausea, retching, and Antiemetics expulsion of proximal duodenal Antiemetics are drugs that block the and gastric contents.6,7,16 Nausea is vomiting reflex9,23,24 by impeding the conscious recognition of sub- neurotransmission at central (CRTZ, conscious excitation in an area of emetic center) and peripheral (gasthe medulla that is closely associ- trointestinal epithelium) recepated with the vomiting center. This tor sites. These drugs are classified excitation is caused by irritative based on the type of receptor they impulses coming from the gastroin- block (TABLE 1). However, antiemettestinal tract, lower brain, or cerebral ics have the potential to prolong gascortex.15,17–19 Ptyalism, tachycardia, trointestinal infections, predispose nervousness, hiding or seeking patients to such infections, and preattention, shivering, and yawning vent toxin elimination by decreasare all characteristic signs of nau- ing gastrointestinal motility. The use sea triggered by general activation of most of these drugs in animals of the sympathetic and parasympa- is off-label, and some dosages are thetic branches of the autonomic extrapolated from the human medinervous system. Hypersalivation cal literature (TABLE 2). stimulates swallowing, which stimulates relaxation of the gastroesopha- Phenothiazines geal sphincter. The bicarbonate-rich Phenothiazines are broad-specsaliva secreted by the salivary glands trum antiemetics that have antidoin the mouth lubricates the esopha- paminergic and antihistaminergic gus and helps neutralize the stom- properties at low doses in the ach’s acidic environment before CRTZ and anticholinergic effects at vomiting.8,13 Before retching, abo- higher doses at other central sites, ral gastric and esophageal motility including the emetic center.9 These diminishes and the lower esopha- drugs also block norepinephrine at peripheral α-adrenergic recepgeal and pyloric sphincters relax.

Retching is the second phase of tors. Drugs in this group include vomiting and begins with the onset chlorpromazine, prochlor perazine, of a retrograde giant contraction.20,21 and acetylpromazine. Common This contraction is a single-phase, ret- adverse effects in small animals, rograde, peristaltic motion that emp- especially dogs, include ataxia, ties the proximal duodenal contents hypotension, and excessive sedainto the stomach.20–22 It is followed by tion. Generalized central nervous deep inspiratory movements, force- system (CNS) stimulation, aggresful contractions of the abdominal siveness, violent behavior, extrapymuscles and diaphragm, and closure ramidal effects, and seizures are of the glottis. These actions produce rare. Fluid therapy is indicated in

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Vomiting CE patients undergoing phenothiazine therapy because of the vasodilatory properties of these drugs.

Anticholinergics Anticholinergic drugs block cholinergic afferent pathway transmission from the gastrointestinal tract (peripheral action) and the vestibular system to the emetic center (central action).9 Scopolamine and isopropamide are centrally acting anticholinergics that cross the blood–brain

TABLE 1

barrier. They have a short duration of action and can cause excitement in cats. Peripherally acting anticholinergics include propantheline and methscopolamine. Isopropamide and propantheline are the drugs in this group that are most commonly used in small animals for vomiting related to motion sickness.25 Side effects reported in humans and small animals include xerostomia (dry mouth), sedation, visual disturbances, drowsiness, dysphoria, confusion, gastrointestinal ileus, and disorientation.9,26

Vomiting Reflex Components, Receptors, and Controlling Neurotransmitters and Medications

Receptor

Receptor Agonists

Receptor Antagonists

Chemoreceptor trigger zone D2-Dopaminergic

Dopamine

Metoclopramide Trimethobenzamide Chlorpromazine

Prochlorperazine Acetylpromazine

Haloperidol Droperidol

M1-Cholinergic

Acetylcholine

Propantheline Isopropamide Prochlorperazine

Chlorpromazine Scopolamine

Methscopolamine Acetylpromazine

H1-Histaminergic

Histamine

Diphenhydramine Dimenhydrinate Meclizine

Prochlorperazine Chlorpromazine

Acetylpromazine Promethazine

α2-Adrenergic

Norepinephrine

Prochlorperazine Chlorpromazine

Yohimbine Acetylpromazine

5-HT3-Serotonergic

Serotonin

Ondansetron Dolasetron

Mirtazapine Propofol

Metoclopramide Granisetron

ENKμ,δ-Enkephalinergic

Met-enkephalin Leu-enkephalin

Butorphanol

Neurokinin-1 antagonist

Substance P

Maropitant

Serotonin

Diphenhydramine

Dimenhydrinate

Meclizine

α2-Adrenergic

Norepinephrine

Prochlorperazine

Chlorpromazine

Yohimbine

Glucocorticoid receptors

Dexamethasone

Cyproterone

Mifepristone

Neurokinin-1 antagonist

Substance P

Maropitant

M1-Cholinergic

Acetylcholine

Propantheline Isopropamide Prochlorperazine

Chlorpromazine Scopolamine

Methscopolamine Acetylpromazine

H1-Histaminergic

Histamine

Diphenhydramine Dimenhydrinate Meclizine

Prochlorperazine Chlorpromazine Diazepam

Cyclizine Promethazine

5-HT3-Serotonergic

Serotonin

Ondansetron Dolasetron

Mirtazapine Metoclopramide

Granisetron

Neurokinin-1 antagonist

Substance P

Maropitant

D2-Dopaminergic

Dopamine

Metoclopramide Trimethobenzamide Chlorpromazine

Prochlorperazine Acetylpromazine

Haloperidol Droperidol

5-HT4-Serotonergic

Cisapride Metoclopramide Serotonin

Piboserod

M2-Cholinergic

Acetylcholine

Propantheline Isopropamide Prochlorperazine

Chlorpromazine Scopolamine

Methscopolamine Acetylpromazine

Motilin

Erythromycin Motilin

QuickNotes

Emetic center 5-HT1A-Serotonergic

Vomiting is a neurologically mediated reflex that depends on neural or humoral activation of the emetic center.

Vestibular apparatus

Vagal afferents

Vagal efferents

—

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Antihistamines Antihistamines can intercept cholinergic and histaminic nerve transmission responsible for vestibular stimulation of the vomiting center.25 Drugs in this classification include diphenhydramine, dimenhydrinate, and meclizine.

These drugs display H 1-antihistaminergic properties and are mainly used to control the clinical signs of motion sickness. Mild sedation, xerostomia, and drowsiness are some of the adverse effects. Meclizine can be teratogenic if administered at high doses.25 Cats do not have histamine receptors in the CRTZ, and antihistaminic drugs do not control their vomiting.27

Serotonin Antagonists

QuickNotes Antiemetics are drugs that block specific superficial cell receptor sites, consequently disrupting the vomiting reflex.

Serotonin antagonists are specific inhibitors of 5-HT-serotonergic receptors. They control vomiting by acting on receptors located on the periphery of vagal nerve terminals and centrally on the CRTZ.25,26 These receptors are normally stimulated by serotonin released from the enterochromaffin cells of the small intestine in response to damage to the gastrointestinal mucosa. Ondansetron, a member of this class of antiemetic drugs, has been shown to control vomiting in dogs28,29 and is used in dogs receiving radiation and chemotherapy when metoclopramide and other antiemetics fail to control vomiting.28,29 Dolasetron, another member of this group, acts on receptors in the CRTZ.25 Both of these drugs are used extensively in human medicine, and they seem to be safe antiemetic alternatives in veterinary medicine.30,31 However, they are not effective in controlling vomiting caused by motion sickness.25,26 Side effects of these drugs that have been reported in people include electrocardiographic changes, including PR and QT prolongation and QRS widening, that are believed to be caused by sodium channel blockage by dolasetron metabolites. Diarrhea, headache, dizziness, and musculoskeletal pain have been reported as well. These medications can be expensive.

Substituted Benzamides Substituted benzamides exert antiemetic effects through different mechanisms. Some, such as metoclopramide and trimethobenzamide, antagonize dopamine receptors in the CNS and block 5-HT3-serotonergic receptors when administered

126

at high concentrations.9,25 Metoclopramide is known for its potent dopaminergic antagonism, but trimethobenzamide, which is also a weak antihistamine, has not been a very effective antidopaminergic agent clinically. Metoclopramide has more action on D2-dopaminergic receptors than trimethobenzamide and is 20 times more potent than phenothiazines.7 As a result, metoclopramide should not be used in patients receiving dopamine.12 Cisapride, another substituted benzamide, activates neuronal 5-HT4 receptors, which facilitates gastric emptying. Metoclopramide also activates neuronal 5-HT4 receptors and blocks 5-HT3 -serotonergic receptors, increases the lower esophageal sphincter tone, and enhances aboral gastrointestinal motility; therefore, these drugs are classified as prokinetics as well.9 Adverse effects of these drugs include CNS excitement and behavioral changes, especially during rapid intravenous administration or if given at high doses. Metoclopramide controls peripherally induced and humorally mediated vomiting due to numerous conditions, but it should be avoided if gastrointestinal obstruction is suspected because its prokinetic properties could predispose these patients to gastric or intestinal perforation. This contraindication also applies to cisapride.

Butyrophenone and Benzimidazole Derivatives Butyrophenone derivatives (e.g., haloperidol, droperidol) are potent dopamine antagonists in the CRTZ and are used as tranquilizers.9 Their side effects are very similar to those of phenothiazines. The benzimidazole derivatives antagonize dopamine receptors in the gastrointestinal smooth muscle and display prokinetic properties like those of metoclopramide,32 but their use in veterinary medicine is minimal if any.

Opioids Enkephalins—endogenous opiates belonging to the endorphin family—are believed to have antiemetic properties. Neurons containing enkephalins have been identified near the CRTZ and the emetic center.33 Evidence suggests that opioid κ and/or μ receptors are present in the vomiting center and are involved in inhibition of emesis in dogs and cats.34 Butorphanol, a pri-

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Vomiting CE TABLE 2

Most Common Antiemetics Used in Small Animal Medicine

Drugs

Site of Action

Dosage

Side Effects

Prochlorperazinea,13

CRTZ and emetic center

Dogs and cats: 0.1–0.5 mg/kg SC or IM q6–8h

Hypotension, sedation

Chlorpromazinea,2,13

CRTZ and emetic center

Dogs: 0.1–0.5 mg/kg SC, IM, or IV q6–8h Cats: 0.2–0.5 mg/kg SC, IM, or IV q6–8h

Hypotension, sedation

Yohimbinea,2

CRTZ and emetic center

Dogs: 0.25–0.5 mg/kg SC or IM q12h

Hypotension, sedation

Metoclopramidea,2,13

CRTZ, GI smooth muscle

Dogs: 0.1–0.4 mg/kg PO, SC, or IM q6h Cats: 0.2–0.4 mg/kg PO, or SC q6–8h CRI: 1–2 mg/kg/day

Extrapyramidal signs, constipation

Trimethobenzamide2,13

CRTZ

Dogs: 3 mg/kg IM q8–12h

Allergic reactions

CRTZ

Dogs and cats: 2–4 mg/kg PO or IM q8h

Sedation, GI effects

CRTZ

Dogs and cats: 4–8 mg/kg PO q8h

Sedation, GI effects

CRTZ

Dogs and cats: 4 mg/kg PO q24h

Sedation, xerostomia, tachycardia

Propanthelinea

Parasympathetic nervous system

Dogs and cats: 0.25 mg/kg PO q8h

Gastric retention, ileus, tachycardia

Isopropamideb

Parasympathetic nervous system

Dogs and cats: 0.2–0.4 mg/kg PO q8–12h

Gastric retention, ileus, tachycardia

Ondansetrona,2

CRTZ and vagal afferent neurons

Dogs: 0.11–0.176 mg/kg slow IV push q24h Cats: 0.1–0.15 mg/kg slow IV push q24h

Sedation

Dolasetrona

CRTZ

Dogs: 0.6 mg/kg IV q24h or 0.5 mg/kg PO, SC, or IV q24h Cats: 0.6 mg/kg IV q12h or 0.6–1 mg/kg PO q12h

Electrocardiogram changes

Mirtazapinea

CRTZ and vagal afferent neurons

Dogs: 0.6 mg/kg PO q24h, not to exceed 30 mg/day Cats: 3–4 mg/cat PO q72h

Sedation, ataxia, depression, vocalization

CRTZ and emetic center

Dogs: 1 mg/kg SC q24h up to 5 days or 2 mg/kg PO q24h up to 5 days

Injection site soreness, ataxia, anorexia, diarrhea

Myenteric neurons

Dogs: 0.1–0.5 mg/kg PO q8h Cats: 0.1–1.0 mg/kg or 5 mg (total dose) PO q8–12h

None

GI smooth muscle

Dogs and cats: 0.5–1.0 mg/kg IV q8h, up to 5.0 mg/kg PO q8h

Vomiting at antimicrobial doses (15 mg/ kg tid)

Emetic center

Dogs: 0.2–0.4 mg/kg IM 30 min before cisplatin infusion

Sedation, ataxia, anorexia, diarrhea

CRTZ

None reported in veterinary medicine

Apnea, hypotension, seizurelike signs

Emetic center, medulla

Dogs: 0.1 mg/kg SC or IV before chemotherapy

GI ulceration

Vestibular system suppression

0.1–0.2 mg/kg PO q6h

Sedation

α2-Adrenergic antagonists

D2-Dopaminergic antagonists

H1-Histaminergic antagonists Diphenhydraminea,2,13 Dimenhydrinate Meclizine

a,2,13

a

M1-Cholinergic antagonists

5-HT3-Serotonergic antagonists

NK1-Neurokinin antagonist Maropitant40

5-HT4-Serotonergic antagonist Cisapridea,2

Motilin agonist Erythromycina,2

Opioid Butorphanola,13 Others Propofola Dexamethasone a

Diazepam

13

a

Plumb DC. Veterinarian Drug Handbook. 6th ed. Ames, IA: Wiley-Blackwell; 2008. b Richter KP. Treating acute vomiting in dogs and cats. Vet Med 1992;87(8):814-818.

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marily κ and σ agonist, is used to prevent vomiting related to cisplatin therapy in dogs.35,36

Neurokinin Antagonists

QuickNotes Phenothiazines are broad-spectrum antiemetics that have antidopaminergic and antihistaminergic properties in the CRTZ and anticholinergic effects in the emetic center.

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Neurokinin (NK1) antagonists are a new group of antiemetics that includes maropitant, an agent developed for dogs that acts as a ligand for the substance P receptors located in many areas of the brain, including the emetic center and CRTZ.37 It is believed that the substance P–NK1 receptor complex is in the final common pathway of the neural and humoral pathways of the vomiting reflex.38 Studies in dogs have showed that maropitant prevents vomiting caused by peripheral and central emetogens, including apomorphine, cisplatin, and syrup of ipecac,39 and clinical conditions such as pancreatitis and gastroenteritis.39 Maropitant is also effective against vomiting caused by motion sickness.39 Adverse effects reported with this drug include ataxia, anorexia, diarrhea, and injection site soreness.40 This drug should not be used in dogs younger than 16 weeks because bone marrow hypoplasia has been reported.40

Other Drugs Other drugs used to control vomiting centrally include yohimbine, diazepam, dexamethasone, propofol, and mirtazapine. Yohimbine, a pure α2-adrenergic antagonist, is a very potent antiemetic used in dogs and cats. It may cause CNS excitement, excessive sedation, muscle tremors, tachypnea, ptyalism, and hyperemic mucous membranes.36 Diazepam relieves nausea and vomiting in people.41 Studies with animal models and clinical trials in human medicine suggest that this drug suppresses the vestibular system.41–43 The antiemetic properties of corticosteroids are incompletely understood, but their mechanism involves the activation of glucocorticoid receptors in the medulla, especially the emetic center in cats.44 Dexamethasone has been shown to be useful in controlling chemotherapy-associated nausea and vomiting in human patients45 and dogs.45,46 Propofol, an alkylphenol derivative, is used as an antiemetic in people with chemotherapy-associated nausea and vomiting that is unresponsive to serotonin antagonists or dexamethasone.47,48 It has been proposed that its antiemetic mechanism involves reduction of the serotonin concentration in the CRTZ via γ-aminobutyric acid activity and 5-HT3 serotonin receptor antagonism.49

Mirtazapine is a piperazinoazepine drug used as an antidepressant in people. It antagonizes central presynaptic α 2-receptors and blocks serotonin receptors.50 It is a weak 5-HT1 serotonin receptor antagonist, a potent 5-HT2 and 5-HT3 serotonin receptor antagonist, and an H1-histamine antagonist.50 It is used to control chemotherapy-associated nausea and vomiting in humans50,51 and, more recently, in small animals.

Treatment of Common Vomiting Conditions BOX 1 lists several conditions and diseases that commonly cause vomiting.

Gastritis or Gastric Ulceration Treatment to manage vomiting caused by gastritis or gastric ulceration must include proper fluid therapy and gastric mucosal protection.

Many clinicians use broad-spectrum antiemetics because they cover local and peripheral receptors. Chlorpromazine, serotonin antagonists, and metoclopramide are good options. Maropitant seems to work extremely well in dogs. If vomiting is associated with gastrointestinal ulceration due to NSAID administration, therapy with misoprostol, a prostaglandin E1 (PGE) analog, may be effective in controlling both the ulcerative lesion and vomiting as a secondary problem.52 Proton pump inhibitors and H2-histamine antagonists provide more complete inhibition of gastric acid secretion in severe cases of ulceration.12,25,53 If Helicobacter spp are the underlying cause of ulceration, appropriate antibiotic therapy and antacids should relieve the clinical signs of the infection.

Patients with neoplastic diseases often have gastrointestinal ulceration. Mast cell tumors of any stage, grade, and size can cause vomiting in dogs by increasing the plasma histamine concentration.16,54 Histamine acts on the CRTZ and the gastric mucosa. Mast cell tumor ulceration and its effects are treated with H2-histamine antagonists. Tumor size and histamine release in dogs are controlled with the administration of corticosteroids.12,55

Pancreatitis Pancreatitis causes ileus due to intestinal inflammation, resulting in direct afferent input to the vomiting center.12 Metoclopramide is the most common antiemetic used in these patients because it acts centrally and peripherally. In dogs, phenothiazines, 5-HT 3 -serotonergic

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Vomiting CE antagonists, and maropitant can be useful if metoclopramide fails to control vomiting.

Emesis caused by cancer chemotherapy and other drugs (e.g., digitalis) is mediated by 5-HT3-serotonergic receptors.2,12,25 In humans, the chemotherapeutic drugs most commonly associated with vomiting include cisplatin, cyclophosphamide, dacarbazine, and doxorubicin.56 Drugs with 5-HT3-serotonergic antagonist properties, especially the serotonin antagonists ondansetron, granisetron, dolasetron, block these receptors in the CRTZ in cats and in the vagal afferent neurons in dogs.25,26,28,29,57 Metoclopramide is widely used to control chemotherapy-induced vomiting.6,58 The new agent maropitant is also effective in controlling cisplatin-induced vomiting in dogs, and even though there is coexpression of substance P with 5-HT receptors in the primate brain,37 this has not been documented in dogs or cats.

ing inputs from the two vestibular systems (the semicircular canals and the otolith organs); or (3) comparison of input from these systems with the individual’s expectations derived from previous experiences.59 Vomiting caused by motion sickness involves M1-cholinergic and H1-histaminergic receptors,2,11 and treatment should antagonize both receptors.

Phenothiazines like chlorpromazine and prochlorperazine can antagonize both receptors at the same time, but diphenhydramine, dimenhydrinate, cyclizine, meclizine, and promethazine are H1-histamine blocking agents only, and they should be combined with a M1-cholinergic receptor blocker for effective control of emetic signals originating from the vestibular apparatus. Maropitant prevents kinetosis in dogs by blocking the final common pathways of the vomiting reflex, including signals from the vestibular system.40 Scopolamine is a muscarinic M1-cholinergic antagonist used to treat motion sickness, but results are not consistent.

Motion Sickness

Uremia

Motion sickness, or kinetosis, is generated from the vestibular apparatus.2,9,11 Studies in humans have revealed that motion sickness is caused by three mechanisms: (1) conflicting inputs from the visual and vestibular systems; (2) conflict-

Uremic toxins cause decreased gastrin clearance and irritate the gastrointestinal mucosa, resulting in ulcerative lesions and gastritis.

When these toxins cross the blood–brain barrier, they stimulate central and peripheral receptors and activate D2-dopaminergic receptors in the CRTZ.2,11 Dopamine antagonists like metoclopramide and chlorpromazine effectively block these receptors.

Diuresis with appropriate fluid therapy and a proton pump inhibitor or H2-histaminergic antagonist helps relieve uremia by diminishing the secretion of hydrogen ions into the stomach, providing protection and promoting mucosal healing.

Chemotherapy and Other Drugs

BOX 1

Most Common Causes of Vomiting in Dogs and Cats Abdominal disorders Dietary factors Disorders of the small and large intestines Disorders of the stomach Drugsa Endocrine disorders ❯ Hypoadrenocorticism ❯ Hypoparathyroidism Neurologic disorders Parasitism ❯ Ollulanus tricuspis in cats ❯ Physaloptera ❯ Salmon poisoning (Neorickettsia helminthoeca) Systemic diseases Toxins, chemicals, and poisons a Almost any drug can cause vomiting, especially if given orally.

QuickNotes Vomiting caused by motion sickness involves M1-cholinergic and H1-histaminergic receptors, and treatment should antagonize both receptors.

Gastrointestinal Motility Disorders Prokinetics—cisapride, metoclopramide, and erythromycin—should be used to control vomiting due to nonobstructive delayed gastric emptying. These drugs exert their effects on different receptors. Cisapride, the most effective prokinetic agent available,11 lacks direct antiemetic effects but stimulates 5-HT4-serotonergic receptors.60 Metoclopramide’s antagonism of D2-dopaminergic receptors enables it to stimulate motility in areas where these receptors are present (the higher gastrointestinal tract, lower esophageal sphincter, stomach, and duode-

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FREE CE Vomiting

QuickNotes Patients with vomiting of undetermined etiology must be treated with the safest approach possible once systemic diseases have been ruled out.

130

num).2,11 Erythromycin, a macrolide used for its antimicrobial properties, is useful as a prokinetic at low doses.2,11 In dogs, it stimulates the release of motilin, which initiates phase III of the migrating myoelectric complex,61,62 the sequence of motor activity during the interdigestive period in the small bowel.63 This cyclic pattern originates in the gastric antrum and extends over the entire length of the small intestine.62,63 The third and final phase of this pattern is generally associated with the propulsion of ingesta.64,65 It is unknown whether cats can benefit from this effect.

Dogs that vomit bile in the morning before eating may have bilious vomiting syndrome.

This is a condition characterized by grass ingestion, vomiting, and lack of other definitive clinical signs. It mostly occurs in the morning and is believed to be commonly associated with gastritis, inflammatory bowel disease, and bile and gastroesophageal reflux. Affected patients usually respond to a single evening dose of cisapride, metoclopramide, or erythromycin.

Undetermined Etiology Patients with vomiting of undetermined etiology must be treated with the safest approach possible once systemic diseases (e.g., liver disease, renal disease, endocrine disease) have been ruled out. Patients that are uncomfortable from excessive vomiting or are at high risk for aspiration pneumonia and have not been exposed to a toxic agent should be treated with antiemetics when available. α2-Adrenergic antagonists and D2-dopaminergic receptors are first-line antiemetics. Maropitant is a good alternative not only because it seems to block impulses in the final common pathways of the vomiting reflex but also because it is administered once daily, dogs seem to tolerate it fairly well, and, so far, adverse effects are minimal. 5-HT3-serotonergic antagonists have become very popular over the past few years and have good results. The addition of other drugs to antiemetic therapy should be considered if vomiting becomes refractory in these patients.

References 1. Tams TT. A diagnostic approach to vomiting in dogs and cats. Vet Med 1992;87(8):785-792.

2. Washabau RJ, Elie S. Antiemetic therapy. In: Kirk RW, Bonagura JD, eds. Kirk’s Current Veterinary Therapy XII Small Animal Practice. Philadelphia: WB Saunders; 1995:679-684.

3. Andrews PLR, Rapeport WG, Sanger GJ. Neuropharmacology of emesis induced by anti-cancer therapy. Trends Pharmacol Sci 1988;9:334341.

4. Johnson SE. Clinical pharmacology of antiemetics and antidiarrheals.

Proc of the Kal Kan Waltham Symp Treat Small Anim Dis 1984;8:7-15.

5. Merrifield KR, Chaffee BJ. Recent advances in the management of nausea and vomiting caused by antineoplastic agents. Clin Pharm 1989;8:187-199.

6. Leib MS. Acute vomiting: a diagnostic approach and symptomatic management. In: Kirk RW, Bonagura JD, eds. Kirk’s Current Veterinary Therapy XI Small Animal Practice. Philadelphia: WB Saunders; 1995:583587.

7. Burrows CF. Vomiting and Regurgitation in the Dog: A Clinical Perspective. Lehigh, Pennsylvania. ALPO Pet Center; 1990:18-38. Viewpoints in Veterinary Medicine.

8. Guyton AC, Hall JE. Textbook of Medical Physiology. 9th ed. Philadelphia: WB Saunders; 1996.

9. Adams HR. Veterinary Pharmacology and Therapeutics. 8th ed. Ames: Iowa State University Press; 2001.

10. Cunningham JG. Textbook of Veterinary Physiology. 3rd ed. Philadelphia: WB Saunders; 1997.

11. Richter K. Approach to acute vomiting. Proc WVC 2004. Accessed January 2009 at vin.com/Members/Proceedings/Proceedings.plx?CID=wv c2004&PID=pr05345&O=VIN. 12. Simpson KW. Managing persistent vomiting. Proc ACVIM 2003. Accessed January 2009 at vin.com/Members/Proceedings/Proceedings.plx?

CID=acvim2003&PID=pr03873&O=VIN. 13. Strombeck DA, Guilford WG. Vomiting: pathophysiology and pharmacology control. In: Strombeck DA, Guilford WG, Center SA, et al, eds.

Strombeck’s Small Animal Gastroenterology. 3rd ed. Philadelphia: WB Saunders; 1996:256-260.

14. Willard MD. Some new approaches to the treatment of vomiting. JAVMA 1984;184:590.

15. Miller AD, Leslie RA. The area postrema and vomiting. Front Neuroendocrinol 1994;15(4):301-320.

16. Twedt DC. Vomiting. In: Ettinger SJ, Feldman EC, eds. Textbook of Veterinary Internal Medicine. 6th ed. Philadelphia: WB Saunders; 2005:132136.

17. Miller AD. Central mechanisms of vomiting. Dig Dis Sci 1999; 44(8 suppl):31S-43S. 18. Miller AD, Nonaka S, Jakus J, et al. Modulation of vomiting by the medullary midline. Brain Res 1996;737(1-2):51-58.

19. Miller AD, Nonaka S, Jakus J. Brain areas essential or non-essential for emesis. Brain Res 1994;647(2):255-264.

20. Lang IM, Dana N, Medda BK, et al. Mechanisms of airway protection during retching, vomiting, and swallowing. Am J Physiol Gastrointest Liver Physiol 2002;283(3):G529-G536.

21. Sarna SK, Otterson MF. Small intestinal physiology and pathophysiology. Gastroenterol Clin North Am 1989;18(2):375-404.

22. Furukawa N, Hatano M. An acute experiment on retrograde intestinal peristalsis with emesis using decerebrated dogs. J Auton Nerv Syst 1998;70(1-2):56-65.

23. Peroutka SJ, Snyder SH. Antiemetics: neurotransmitter receptor binding predicts therapeutic actions. Lancet 1982;1(8273):658-659.

24. Costall B, Naylor RJ. Neuropharmacology of emesis in relation to clinical response. Br J Cancer Suppl 1992;19:S2-S8.

25. Dowling PM. GI therapy: when what goes in won’t stay down. Proc WVC 2003. Accessed January 2009 at vin.com/Members/Proceedings/ Proceedings.plx?CID=wvc2003&PID=pr03480&O=VIN. 26. Flake ZA, Scalley RD, Bailey AG. Practical selection of antiemetics. Am Fam Phys 2004;69:1169-1174,1176.

27. King GL. Animal models in the study of vomiting. Can J Physiol Pharmacol 1990;68:260.

28. Martirosov KS, Grigor’ev IuG, Borovkov MV, Zorin VV. Experimental study of the role of blocking 5-HT3-receptors of serotonin and D2-receptors of dopamine in the mechanism of early radiation vomiting in dogs.

Radiats Biol Radioecol 2002;42(1):75-79.

29. Martirosov KS, Grigor’ev IuG, Borovkov MV, Zorin VV. Comparative experimental study of antiemetic action of lantranum in radiation-induced vomiting and vomiting caused by apomorphine. Radiats Biol Radioecol 2003;43(1):60-64.

30. Product information: Zofran. Research Triangle Park, NC: GlaxoSmithKline; 2006.

31. Andrews PLR, Naylor RJ, Joss RA. Neuropharmacology of emesis and its relevance to anti-emetic therapy: consensus and controversies. Support Care Cancer 1998;6:197-203.

32. Takahashi T, Kurosawa S, Wiley JW, et al. Mechanism for the gastrokinetic actions of domperidone. Gastroenterology 1991;101:703-710.

33. Kolh RL, MacDonald S. New pharmacologic approaches to the prevention of space/motion sickness. J Clin Pharmacol 1991; 31(10):934-946.

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Vomiting CE 34. Kobrinsky NL. Regulation of nausea and vomiting in cancer chemotherapy. A review with emphasis on opiate mediators. Am J Pediatr Hematol Oncol 1988;10(3):209-213.

35. Schurig JE, Florczyk AP, Rose WC, et al. Antiemetic activity of butorphanol against cisplatininduced emesis in ferrets and dogs. Cancer Treat Rep 1982;66(10):1831-1835.

36. Plumb DC. Veterinary Drug Handbook. 4th ed. Ames: Iowa State Press-Blackwell; 2002.

37. Davis KL, Charney D, Coyle JT, Nemeroff C. Neuropsychopharmacology: The Fifth Generation of Progress. 5th ed. Philadelphia: Lippincott Williams & Wilkins; 2002;169-177.

38. Hornby PJ. Central neurocircuitry associated with emesis. Am J Med 2001;111(suppl 8A):106S-112S. 39. Benchaoui HA, Cox SR, Schneider RP, et al. The pharmacokinetics of maropitant, a novel neurokinin type-1 receptor antagonist in dogs. J Vet Pharmacol Ther 2007;30(4):336-344.

40. Product information: Cerenia. New York: Pfizer Animal Health: 2006.

41. McClure JA, Lycett P, Baskerville JC. Diazepam as an anti-motion sickness drug. J Otolaryngol 1982;11(4):253-259.

42. Sekitani T, McCabe BF, Ryu JH. Drug effects on the medical vestibular nucleus. Arch Otolaryngol 1971;93:581-589.

43. Zanjoc TP, Roland PS. Vertigo and motion sickness. Part II: pharmacologic treatment. Ear Nose Throat J 2006;85(1):25-35.

44. Ho GM, Ho ST, Wang JJ, et al. Dexamethasone has a central antiemetic mechanism in decerebrated cats. Anesth Analg 2004;99(3):734-739.

45. Dexamethasone alone or in combination with ondansetron for the prevention of delayed nausea and vomiting induced by chemotherapy. The Italian Group for Antiemetic Research. N Engl J Med 2000;342(21):1554-1559.

46. Fukui H, Yamamoto M. Methotrexate produces delayed emesis in dog: a potential model of delayed emesis induced by chemotherapy. Eur J Pharmacol 1999;372:261-267.

47. Borgeat A, Wilder-Smith OH, Saiah M, et al. Subhypnotic doses of propofol possess direct antiemetic properties. Anesth Analg 1992;74:539-541.

48. Gan TJ, El-Molem H, Ray J, et al. Patient-controlled antiemesis: a randomized, double-blind comparison of two doses of propofol versus placebo. Anesthesiology 1999;90:1564-1570.

49. Cechetto DF, Daib T, Gibson CJ, Gelb AW. The effect of propofol in the area postrema in rats.

Anesth Analg 2001;92:934-942.

50. Pae C. Low-dose mirtazapine may be successful treatment option for severe nausea vomiting. Prog Neuropsychopharmacol Biol Psychiatry 2006;30:1143-1145.

51. Kang H, Kim S, Kim J, et al. Mirtazapine for severe gastroparesis unresponsive to conventional prokinetic treatment. Psychosomatics 2006;47:5.

52. Murtaugh RJ, Matz ME, Labata MA, et al. Use of synthetic prostaglandin E1 (misoprostol) for prevention of aspirin-induced gastroduodenal ulceration in arthritic dogs. JAVMA 1993;202(2):251256.

53. Bersenas AME, Mathews KA, Allen DG, et al. Effects of ranitidine, famotidine, pantoprazole, and omeprazole on intragastric pH in dogs. Am J Vet Res 2005;66(3):425-431.

54. Fox LE, Rosenthal RC, Twedt DC, et al. Plasma histamine and gastrin concentrations in 17 dogs with mast cell tumors. J Vet Intern Med 1990;4:242.

55. Ogilvie GK. Mast cell tumors: hot new diagnostics and treatment! Proc WSAVA 2002. Accessed January 2009 at vin.com/Members/Proceedings/Proceedings.plx?CID=wsava2002&PID =pr02637&O=VIN. 56. American Cancer Society. Nausea and vomiting. Accessed January 2009 at cancer.org/docroot/MBC/content/MBC_2X_Nausea_and_Vomiting.asp?sitearea=MBC. 57. Tucker ML, Jackson MR, Scales MDC, et al. Ondansetron: pre-clinical safety evaluation. Eur J Cancer Clin Oncol 1989;25:S79.

58. Ogilvie GK, Moore AS, Curtis CR. Evaluation of cisplatin-induced emesis in dogs with malignant neoplasia: 115 cases (1984-1987). JAVMA 1989;195:1399.

59. Eyeson-Annan M, Peterken C, Brown B, et al. Visual and vestibular components of motion sickness. Aviat Space Environ Med 1996;67(10):955-962.

60. Gullikson GW, Loeffler RF, Viriña AM. Relationship of serotonin-3 receptor antagonist activity to gastric emptying and motor-stimulating actions of prokinetic drugs in dogs. J Pharmacol Exp Ther 1991;258:103.

61. Itoh Z. Erythromycin mimics exogenous motilin in gastrointestinal contractile activity in the dog. Am J Physiol 1984;247:G688.

62. Granger DN, Barrowman JA, Kvietys PR. Clinical Gastrointestinal Physiology: A Saunders Monograph in Physiology. Philadelphia: WB Saunders; 1985.

63. Thomas EA, Sjovall H, Borstein JC. Computational model of the migrating motor complex of the small intestine. Am J Physiol Gastrointest Liver Physiol 2004;286(4):G564-G572.

64. Kruis W, Azpiroz F, Phillips SF. Contractile patterns and transit of fluid in canine terminal ileum. Am J Physiol 1985;249(2 Pt 1):G264-G270.

65. v Schönfeld J, Evans DF, Goebell H, et al. Comparison of the small bowel motor response to solid and liquid meals in man. Digestion 1997;58(4):402-406.

3 CE CREDITS

CE TEST 1

This article qualifies for 3 contact hours of continuing education credit from the Auburn University College of Veterinary Medicine. Subscribers may take individual CE tests online and get real-time scores at CompendiumVet.com.

Those who wish to apply this credit to fulfill state relicensure requirements should consult their respective state authorities regarding the applicability of this program.

1. Emesis is initiated, controlled, regulated, and organized by the a. higher centers of the brain. b. CRTZ. c. vestibular apparatus. d. emetic center.

2. The vomiting pathways are controlled by a. neurotransmitter–receptor interactions. b. the higher centers of the brain. c. the peripheral nervous system. d. vestibular neurons.

3. ___________ are considered broadspectrum antiemetics because of their effect on multiple receptors. a. Anticholinergics b. Phenothiazines c. Serotonin antagonists d. Opioids 4. Emesis caused by cancer chemotherapy and other drugs is mediated by ___________ receptors. a. D2-dopaminergic

b. M1-cholinergic c. H2-histaminergic d. 5-HT3-serotonergic 5. Which antiemetic is also classified as a prokinetic? a. ranitidine b maropitant c. metoclopramide d. propofol 6. Which condition or pathogen is the least likely to cause gastric ulceration? a. Helicobacter spp b. mast cell tumor c. gastrinoma d. kinetosis 7. Mirtazapine does not antagonize ___________ receptors. a. H1-histaminergic b. 5-HT3-serotonergic c. central presynaptic α2d. D2-dopaminergic

8. ___________ can be used for chemotherapy-associated nausea and/or vomiting, especially when patients do not respond to the newer serotonin antagonists and when multiple medication therapy fails. a. Propofol b. Diazepam c. Mirtazapine d. Dexamethasone 9. Which antiemetic antagonizes neurokinin receptors in many areas of the brain? a. mirtazapine b. maropitant c. dolasetron d. prochlorperazine 10. Select the correct antiemetic–adverse effect pair. a. ondansetron; renal toxicity b. chlorpromazine; hypotension c. metoclopramide; sedation d. meclizine; gastrointestinal perforation

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Understanding

Behavior

CONTINUED FROM PAGE 121

Conclusion FHS has multiple possible etiologies. It requires patience and close communication with the pet’s owner in order to arrive at the correct diagnosis. As with most behavior disorders, References 1. Fears, anxieties and stereotypes. In: Overall K. Clinical Behavioral Medicine for Small Animals. St. Louis: Mosby; 1997:227.

2. Lundgren B. Feline hyperesthesia syndrome. Accessed January 2009 at VeterinaryPartner.com.

3. Psychogenic alopecia/overgrooming: feline. In: Horwitz D, Neilson J. Blackwell’s Five-Minute Veterinary Consult Clinical Companion: Canine and Feline Behavior. Ames: Blackwell Publishing; 2007:425-431.

4. Opioids and opioid antagonists. In: Crowell-Davis S, Murray T. Veterinary Psychopharmacology. Ames: Blackwell Publishing; 2006:212.

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FHS can be controlled but is not likely to be cured. By developing a clear diagnostic plan and following it closely, veterinarians can avoid confusion for the owner and foster a sense of cooperation between the owner and themselves. Overall, this is the true measure of success.

5. Tail chasing and spinning: canine and feline. In: Horwitz D, Neilson J. Blackwell’s Five-Minute Veterinary Consult Clinical Companion: Canine and Feline Behavior. Ames: Blackwell Publishing; 2007:475-483.

6. Selective serotonin reuptake inhibitors. In: Crowell-Davis S, Murray T. Veterinary Psychopharmacology. Ames: Blackwell Publishing; 2006:80-110.

7. Tricyclic antidepressants. In: Crowell-Davis S, Murray T. Veterinary Psychopharmacology. Ames: Blackwell Publishing; 2006:179-206.

8. Benzodiazepines. In: Crowell-Davis S, Murray T. Veterinary Psychopharmacology. Ames: Blackwell Publishing; 2006:34-71.

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CE Article 2

3 CE CREDITS

Squamous Cell Carcinoma

At a Glance Risk Factors and Etiology Page 134

Common Locations and Associated Biologic Behavior of SCC Page 134

Gross Description and Clinical Signs Page 135

Diagnosis Page 136

Distinguishing Features of Cytologic Samples That Contain Squamous Cells Page 137

Treatment Options and Prognosis

S

quamous cell carcinoma (SCC) is a malignant neoplasm arising from squamous epithelium. The skin, oral cavity, and digits are the most common sites of SCC in dogs and cats.1 SCCs account for 15% of skin tumors in cats.2 Most cutaneous SCCs in cats occur on the head (FIGURE 1), often involving the pinna, eyelid, and nasal planum.2 In dogs, less than 5% of cutaneous neoplasms are SCC, and common sites include the legs, scrotum, perineum, nasal planum, and various lightly pigmented areas.1,3 SCCs account for 70% of feline and 25% of canine oral neoplasms and may arise from virtually any surface in the oral cavity, including the gingiva (FIGURE 2), tongue, tonsils, pharynx, lips, and buccal mucosa.1 In a retrospective series evaluating lingual lesions in dogs, more than one-half of the lesions were neoplastic, and 17% of those neoplasms were SCC.4 Of digital tumors in dogs (FIGURE 3), 38% to 50% are SCC, and multiple digits may be involved.5,6 Digital SCC was previously reported to be rare in cats, but a recent study diagnosed SCC in 24% of amputated feline digits.7 Other locations reported to develop SCC in dogs and cats include the FIGURE 1

Page 137

a

Dr. LeRoy discloses that he has received financial support from Novartis Animal Health and Pfizer Animal Health.

Periocular SCC in a cat.

conjunctiva, cornea, nasal passages, larynx, lung, esophagus, bladder, prostate, penis, cervix, vagina, and anal sac.1,8,9 Most SCCs are locally invasive and, in certain areas of the body, exhibit bone invasion and osteolysis. Tumor spread to local lymph nodes may occur, but distant metastases are rare and usually do not occur until late in the disease process. However, certain anatomic locations have a higher rate of metastasis. TABLE 1 lists some common sites of SCC and the biologic behavior associated with those sites.1 A premalignant form of SCC, composed of dysplastic cells that do not cross the epithelial basement membrane, is called SCC in situ.10 Complete excision of an SCC in situ is curative for that lesion, but new lesions may develop in other areas. Two forms of SCC in situ have been reported in dogs and cats: solar keratosis and multicentric SCC in situ (MSCC). The lesions of solar keratosis are usually singular and range from an erythematous, scaly thickening of the skin to shallow, crusting lesions. They occur on lightly haired, nonpigmented skin and are associated with ultraviolet (UV) light expoFIGURE 2

Courtesy of Dr. Kosarek

The University of Georgia

Abstract: Squamous cell carcinoma (SCC) is a relatively common, malignant neoplasm of dogs and cats that can arise in a variety of locations. The gross appearance of SCC can be variable and nonspecific, so definitive diagnosis requires microscopic examination of the tissue (cytology or histology). Several treatment modalities exist, but surgical excision, if possible, is regarded as the best treatment option. Early diagnosis and treatment of SCC are key because small, early-stage tumors are the most amenable to treatment and carry the best prognosis.

Courtesy of Carrie E. Kosarek, DVM, MS, DACVIM (Oncology)

❯❯ Julie L. Webb, DVM, DACVP ❯❯ Rachel E. Burns, DVM ❯❯ Holly M. Brown, DVM ❯❯ Bruce E. LeRoy, DVM, PhD, DACVPa ❯❯ Carrie E. Kosarek, DVM, MS, DACVIM (Oncology)

Maxillary gingival SCC in a dog.

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FREE CE Squamous Cell Carcinoma

sure.3 With time and continued exposure to UV light, most solar keratosis lesions can progress to SCC. MSCC, similar to Bowen’s disease in humans, presents as multiple plaque-like or papillary lesions on pigmented, haired skin and is not related to UV light exposure. MSCC is rare in cats and very rare in dogs.1,10 Its progression to SCC seems to be slow, if it occurs at all.

Courtesy of Dr. Kosarek

FIGURE 3

Risk Factors and Etiology

Digital SCC in a dog.

TABLE 1

Older animals are at greater risk for developing SCC, with the average age at presentation being 8 to 10 years for dogs and 10 to 12 years for cats.2,3,10 Prolonged exposure to UV light, lack of skin pigment, and a sparse haircoat all contribute to the development of cutaneous SCC.1 Siamese cats, with their pigmented extremities, may be less likely to develop cutaneous SCC.2 Cats with long haircoats, such as Himalayans and Persians, also have a decreased risk, whereas domestic shorthaired cats are overrepresented.1 Dogs with white haircoats are more susceptible to cutaneous SCC, whereas dogs with dark haircoats appear to be overrepresented in cases of digital tumors.1,6 Rarely has a sex predilection been reported; in one study, female dogs appeared to be at increased risk for development of lingual SCC4, while tonsillar SCC may be more common in male dogs.11,12

The mechanism frequently proposed for cutaneous SCC and its association with UV light involves the tumor suppressor gene p53.13 This gene encodes a protein (p53) that arrests the cell cycle when DNA damage is present, giving the cell time to repair the damage before continuing mitosis. If the damage cannot be repaired, p53 will induce apoptosis of the cell. UV light is a common carcinogen that can mutate the p53 gene. Cells in which the p53 gene is mutated continue replication even if DNA damage is present, leading to the accumulation of other mutations and a greater chance of neoplasia.13 The mutant form of p53 has been detected in 82% of feline pinna SCCs, emphasizing the importance of p53 in preventing solar-induced SCC.13 Few studies investigating carcinogens that may contribute to the development of SCC in cats and dogs have been conducted. Reported risk factors for oral SCC in cats include wearing flea collars and eating canned food (especially tuna-based food).14 Small but statistically insignificant correlations have been found between environmental tobacco smoke and feline oral SCC.14,15 Urban pollutants may increase the risk for tonsillar SCC.3 Another potential contributor to the development of SCC in dogs and cats is chronic inflammation. Chronic dermatosis is a reported risk factor for cutaneous SCC,16 and, although extremely rare, bilateral aural SCC was reported in two dogs that had a history of chronic aural inflammation.17 In addition, multiple corneal SCCs developed in a dog with keratoconjunctivitis sicca.18

Common Locations and Associated Biologic Behavior of SCC

Tumor Location

Local Invasion

Regional Lymph Node Spread

Distant Metastasis

Comments

Skin

Frequent

Rare

Rare

Lymph node spread mostly occurs in poorly differentiated tumors or those present for longer periods

Gingiva

Frequent

Rare

Rare

Frequent bone invasion and destruction

Tongue

Frequent

Common

Rare

Local recurrence common after surgical removal

Tonsil

Frequent

Frequent

Common

Lungs, liver, and spleen are the most common metastatic sites

Cheek/Lip

Common

Rare

Rare

—

Nasal passages

Frequent

Rare

Rare

Bone invasion common

Lung

Frequent

Common

Common

Solitary or multiple masses; metastases to one or multiple digits reported in cats

Digit

Frequent

Common

Common

Bone invasion and destruction common; lungs are the most common metastatic site

134

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Squamous Cell Carcinoma CE

Asynchronous maturation in a neoplastic squamous cell. The mature, fully keratinized cell has retained a large nucleus (arrow; Wright’s stain, 1000×).

Viral etiologies have been linked to certain SCCs in people. Papillomavirus type 16 infection is associated with a significant number of SCCs of the head and neck in humans, particularly in the oropharynx and in patients lacking the risk factors of tobacco and alcohol consumption.19 Papillomavirus DNA has been detected within approximately 20% of canine and feline cutaneous and mucosal SCCs, but the significance of this association has yet to be determined.20,21 Radiation-induced carcinogenesis is well documented in people and animals, as reviewed

by Suit and colleagues in 2007.22 In one study23 evaluating orthovoltage radiotherapy for the treatment of acanthomatous epulides (now called acanthomatous ameloblastomas), seven of 39 dogs (18%) developed second tumors within the radiation field; 71% of the tumors were SCC. However, a more recent study24 found that the risk of developing a second tumor was less than 4%. In this study, only two of 57 dogs that underwent definitive radiation therapy (RT) for acanthomatous epulides developed second tumors, both of which were sarcomas. The authors of the more recent study suggest that the earlier paper may have included patients whose original tumors were SCC, misdiagnosed as acanthomatous epulides.

Gross Description and Clinical Signs In many cases of SCC, the animal presents with a visible mass. The mass may appear as any of the following3: Shallow crusting lesion (often SCC in situ)

Courtesy of Dr. Webb

FIGURE 5

Courtesy of Julie L. Webb, DVM, DACVP

FIGURE 4

Fine-needle aspirate from a cutaneous SCC. A small cluster of cells displays anisocytosis, anisokaryosis, multinucleation, prominent nucleoli (thin arrow), keratohyaline granules (thick arrow), and emperipolesis (arrowhead; Wright’s stain, 1000×).

Deeply ulcerated lesion Proliferative, raised, red plaque Cauliflower-shaped growth The appearance of the lesion may change over time, often progressing from a shallow or ulcerated lesion to a more proliferative, raised tumor. The time from lesion occurrence to diagnosis also varies but is generally prolonged. In two studies of cats with SCC of the nasal planum or pinnae, lesions were reportedly present for a median duration of 3 to 5 months before diagnosis.25,26 Often, the tumor is initially misdiagnosed as an inflammatory or traumatic lesion, and therapies such as antibiotics and corticosteroids may have been used before diagnosis.25 Clinical signs of SCC depend on the tumor’s location. Digital tumors often cause lameness and ulceration of the digit.5 Nasal tumors can cause facial deformity, nasal discharge, and sneezing.

Signs of oral tumors include excess salivation, oral bleeding, anorexia, loose teeth, dysphagia, weight loss, and halitosis.27 Numerous other clinical signs have been reported: coughing and dyspnea with pulmonary tumors, regurgitation with esophageal masses, voice change with laryngeal SCC, and ocular discharge with periocular and ocular tumors.1 Hypertrophic osteopathy is a rare complication with pulmonary SCC.28 There are no consistent abnormal laboratory findings in animals with SCC. One study found that 32% of cats with oral SCC had a neutrophilic leukocytosis, likely reflecting secondary infection of ulcerated masses.27 One

QuickNotes The most common locations for cats and dogs to develop SCC are the skin, digits, and oral cavity, but tumors may also arise at other sites, including the cornea, lungs, esophagus, and bladder.

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Tadpole cells in a cutaneous SCC aspirate (Wright’s stain, 500×).

case of paraneoplastic neutrophilic leukocytosis has been reported with pulmonary SCC,29 and several cases of paraneoplastic hypercalcemia have been documented.30

QuickNotes

Diagnosis

On initial presentation, many SCCs are misdiagnosed as inflammatory or traumatic lesions.

Early diagnosis of SCC is paramount for early therapeutic intervention, which may result in long-term control or cure for affected patients.

SCC may be suspected based on the gross appearance of a lesion and its location, but definitive diagnosis requires microscopic examination of the affected tissue. Cytology is a rapid, easy, noninvasive method that may provide the diagnosis of SCC and is often attempted as the first diagnostic technique, especially for cutaneous lesions. Biopsy with histopathology may be required to obtain a definitive diagnosis if cytology is nondiagnostic or equivocal.

Cytology Several methods may be used to obtain a specimen for cytologic analysis. The best method depends on the lesion location and gross appearance. Fine-needle aspiration is used to obtain material from nodular lesions, whereas surface imprints and scrapings are often used to collect material from shallow or plaquelike lesions. Unfortunately, many SCCs are ulcerated and inflamed, so superficial sampling may retrieve only the inflammation and not the deeper neoplastic cells. Impression smears from biopsy samples also provide material for cytologic examination.

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Courtesy of Dr. Webb

FIGURE 7

Courtesy of Dr. Webb

FIGURE 6

Septic purulent inflammation with squamous cell hyperplasia. A small cluster of dysplastic squamous cells is surrounded by degenerate neutrophils and numerous bacteria. The squamous cells display cytoplasmic basophilia and mild anisocytosis. A binucleated cell is also present (Wright’s stain, 1000×).

As with other epithelial neoplasms, SCCs tend to exfoliate readily, leading to highly cellular samples. The cells may be in closely adherent sheets or clusters, although numerous individual cells are often present. Squamous cells undergo several stages of maturation; thus, a pleomorphic population of cells may be observed. Immature (basal-type) squamous cells are small, round to cuboidal cells with a scant amount of glassy, basophilic cytoplasm and a high nuclear–cytoplasmic ratio. Mature (superficial) squamous cells are large, angular cells with a large amount of lightly basophilic cytoplasm and pyknotic or absent nuclei.31 Keratinized cells have deeply basophilic cytoplasm with angular borders.

Poorly differentiated SCCs consist predominantly of immature cells, and well-differentiated tumors contain more mature cells.

Asynchronous nuclear and cytoplasmic maturation, in which large, fully keratinized cells retain large nuclei, is commonly seen with SCC (FIGURE 4). Other criteria of malignancy found in SCC include prominent anisocytosis and anisokaryosis, multinucleated cells, and variable numbers and sizes of nucleoli.

Keratohyaline granules are frequently present as small, round, cytoplasmic vacuoles concentrated around the nucleus. SCC cells may also display emperipolesis, in which other cells are able to passively penetrate the neoplastic squamous cell and are found within its cytoplasm31 (FIGURE 5). Cells with a long cytoplasmic process resembling a tail, called tadpole cells, are occasionally observed (FIGURE 6).

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Squamous Cell Carcinoma CE

Histology Biopsy of the lesion and histologic analysis are often needed to definitively diagnose SCC, especially if the tumor is poorly differentiated or highly inflamed. If not excisional, the biopsy should always contain the junction of grossly normal and abnormal epithelium, as this is usually the most diagnostic region.

A typical well-differentiated SCC maintains a loose epithelial maturation sequence from basal layer to stratum corneum, but instead of growing toward the skin surface, the neoplastic cells form irregular whorls and cords within the tumor (FIGURE 9). Nests of neoplastic cells surrounded by stroma may have the equivalent of the basal cell layer at the outer edge of the nest and the keratin-producing layer in the center, creating the classic appearance of intensely eosinophilic, densely packed rings of keratin (a keratin pearl, FIGURE 10). In less differentiated tumors, epithelial layering is indistinct, cells are smaller, and keratinization is less likely to be seen. Highly anaplastic SCCs may require special immunohistochemical stains, such as cytokeratin, to positively identify the cell of origin.1

FIGURE 8

Courtesy of Dr. Webb

The cytologic diagnosis of SCC is often complicated by concurrent inflammation. Secondary inflammation, often present when the tumor is ulcerated, may mask the neoplastic cell population. Additionally, primary inflammatory conditions can induce epithelial hyperplasia, creating dysplastic changes, such as increased cytoplasmic basophilia, anisocytosis, and anisokaryosis, that mimic neoplasia (FIGURE 7). Therefore, extreme caution should be used when attempting to diagnose SCC on cytology in a highly inflamed area. Histologic examination of the lesion may be necessary for a definitive diagnosis in these situations.

Other samples containing squamous cells, such as contaminated slides, papillomas, and keratin-producing cysts or tumors (FIGURE 8), must be differentiated from SCC on cytology.

TABLE 2 details features that can help distinguish these lesions from SCC.31

An aspirated sample from a follicular cyst (keratinproducing lesion) containing abundant, anucleate, keratinized squamous cells and keratin debris (Wright’s stain, 200×). Grossly, these lesions contain caseous white material.

analysis, urinalysis, local lymph node evaluation, three-view thoracic radiography, and abdominal imaging (radiography and ultrasonography). The extent of staging that is undertaken is often dictated by the primary tumor location. Advanced imaging techniques, such as computed tomography, may be required to further define the location and extent of the primary tumor, especially for tumors involving the ear canal, oral, and sinonasal cavities.32–34 Imaging is also useful for surgical and radiation treatment planning.

Treatment Options and Prognosis Early diagnosis and implementation of therapy is advised for all patients with SCC, especially because small tumors are more amenable to

Distinguishing Features of Cytologic Samples That Contain Squamous Cells TABLE 2

Staging SCC is typically a locally aggressive neoplasm with a variable potential for distant metastasis.

Diagnostic staging tests that may be advised include routine hematologic and biochemical

a

Lesion

Cytologic Description

SCCa

Pleomorphic population of nucleated squamous cells with numerous features of malignancy

Papillomaa

Mature squamous cells lacking features of malignancy

Keratin-producing cyst or tumorb (FIGURE 8)

Numerous anucleate squamous cells and keratin debris ± cholesterol crystals

Contaminated sample (often due to handling)

A few anucleate squamous cells and a small amount of keratin debris

It may be difficult to differentiate between a well-differentiated SCC and a papilloma on cytology.

Includes epidermal inclusion cysts, follicular cysts, pilomatrixomas, and trichoepitheliomas.

b

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Courtesy of Dr. Webb

FIGURE 9

Nests of neoplastic squamous epithelium in a moderately differentiated SCC (hematoxylin–eosin stain, 400×).

QuickNotes Many SCCs are ulcerated and inflamed.

Superficial sampling (impression smears, scrapings, or swabs) may retrieve only the inflammation and miss the underlying neoplastic cells.

local control. Local treatment options for dogs and cats with SCC include surgery, cryotherapy, RT, plesiotherapy, photodynamic therapy (PDT), and intratumoral chemotherapy. Systemic therapy, such as chemotherapy and cyclooxygenase-2 (COX-2) inhibitors, may be advised for patients with SCCs that are inoperable, are poorly differentiated, have metastasized at the time of diagnosis, or are in a location with a reportedly aggressive biologic behavior (TABLE 1). It is important to note that, with certain forms of SCC (i.e., those induced by UV light), cellular damage may already be present at other sites.

Therefore, new lesions may develop even with excellent local control of the primary lesion.

Surgical Excision Surgical excision is the primary treatment option for most patients with SCC. The ability to completely excise the tumor depends on factors such as the size and location of the tumor.

In a retrospective study25 evaluating response to therapy (surgery, RT, or cryotherapy) in 61 cats with nasal planum or pinna SCC, surgery provided the longest disease-free interval, with a median of 594 days. Early surgical intervention is also advised for digital tumors.

Digital amputation resulted in complete tumor control for all but one of 21 dogs with subungual SCC.35 If complete surgical excision is not possible, adjuvant therapies may be pursued.

Cryotherapy Cryotherapy may be considered for local control of small, superficial tumors or tumors that

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are incompletely excised. It is inexpensive and readily available and provides excellent cosmetic results. Studies have reported that cryotherapy provides good local control for 1 year or longer for SCCs of the cornea.18,36 For the pinna and nasal planum, cryotherapy provided a median disease-free interval of 254 days in 11 cats.25 In a larger study37 of cats with nasal planum SCC treated with cryotherapy, the median remission time was 26.7 months.

Radiation Therapy Definitive RT is a local treatment modality that is generally recommended as an adjuvant treatment for incompletely excised tumors or as a primary treatment for inoperable tumors. In the case of SCC, RT is most commonly employed for tumors of the nasal planum, nasal cavity, and oral cavity. The response to definitive RT for dogs with oral SCC varies with the size of the tumor: small, early-stage tumors had the best response and the longest progression-free intervals38 (FIGURE 11). In cats with nasal planum SCC treated with definitive RT, the 1- and 5-year survival rates were 60% and 10%, respectively.39 In dogs, nasal planum tumors treated with RT recurred in an average of 2 to 3 months, and the median survival time was 6 months.40,41 The median survival time of eight dogs with tonsillar SCC treated with surgery plus definitive RT was 110 days.11 Protocols vary among institutions; however, most protocols involve low-dose fractions (3 to 4 Gy) given daily to every other day over a 3- to 4-week period. The side effects of these protocols are generally mild and limited to acute reactions such as mucosal inflammation. No radiation-induced tumors have been specifically reported with these protocols, but any RT has the potential to induce neoplasia.

Palliative RT typically involves a total of three to four treatments given at a higher dose per fraction than definitive RT. The goals of palliative RT are to provide pain relief, stabilize tumor growth, or improve dysfunction associated with the tumor. Palliative RT may be recommended for patients for which a cure is not possible due to advanced local or metastatic disease or other severe illness. Unfortunately, reports evaluating the efficacy of palliative RT in dogs and cats with SCC are limited, and the few that exist are not encouraging. A 2001 study evaluating palliative RT in seven cats with nonresectable oral SCC found that 87% of the cats had tumor pro-

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Squamous Cell Carcinoma CE gression or acute radiation side effects, with a mean survival time of only 60 days.42

FIGURE 10

Courtesy of Dr. Webb

Plesiotherapy Plesiotherapy involves the topical application of a radiation source to the target lesion.

Topical radiation doses drop off significantly after a depth of 2 mm; therefore, the use of plesiotherapy is limited to superficial or incompletely excised tumors, particularly those of the nasal planum or ocular region. In a recent retrospective study26 evaluating the efficacy of strontium-90 plesiotherapy for cats with nasal planum SCC, 13 of 15 cats achieved a complete response with a median disease-free interval of 692 days. Excellent cosmetic results were also obtained. Strontium-90 plesiotherapy has also been used to treat SCC in dogs.43

A single nest of neoplastic squamous epithelial cells surrounded by fibrous stroma (keratin pearl; hematoxylin–eosin stain, 400×). This is a common finding in well-differentiated SCCs.

Chemotherapy

volume, and 62% of the dogs were euthanized because of progressive disease.12 There are few reports of the use of intratumoral chemotherapy for cats and dogs with SCC.48–50 Intratumoral therapy with a cisplatin analog was ineffective in cats with oral SCC, many of which experienced signs of toxicity ranging from lethargy and inappetence to acute anaphylactoid reactions.49 In comparison, intratumoral treatment with carboplatin appeared safe and effective for cats with nasal planum SCC.48 In a study of 13 dogs with cutaneous SCC treated with intratumoral sustained-release chemotherapy (5-fluorouracil or cisplatin), all the dogs had a 50% or greater response, and 54% achieved a complete response.50 The mean disease-free interval was 153 weeks. The use of chemotherapeutics as sensitizers before RT has also been evaluated in dogs and cats with SCC. Cisplatin combined with RT has shown some promise in dogs with nasal SCC,51 while results of combining gemcitabine with RT are less encouraging.52,53

SCCs generally are not considered chemoresponsive tumors; however, chemotherapy may be considered under certain circumstances.

For example, chemotherapy may be advised for tumors that are inoperable, anaplastic, or metastatic at the time of diagnosis. Single-agent or combination therapy protocols containing bleomycin, cisplatin, carboplatin, cyclophosphamide, doxorubicin, and 5-fluorouracil have been evaluated.12,47 In 16 dogs with tonsillar SCC treated with multidrug chemotherapy, there was no appreciable reduction in tumor

COX-2 is an inducible enzyme responsible for the production of inflammatory prostaglandins.

Overexpression of COX-2 has been implicated in the progression of certain cancers, specifically carcinomas. Several studies in dogs and cats have reported increased expression of COX-2 in SCCs in various locations.54–58 In light of these findings, the role of COX-2 inhibitors in the management of SCC needs to be further explored.

Photodynamic Therapy PDT is yet another local treatment modality that has been used for treatment of SCC. The process involves the topical administration or intravenous injection of a photosensitizer that preferentially accumulates in neoplastic cells.

Once activated by light of a specific wavelength, the photosensitizer causes cytotoxicity and tissue necrosis. Studies of intravenous PDT 44,45 in dogs and cats with oral and cutaneous SCC have shown moderate to good response rates (62% to 73% of patients experience a cure or good local control) that last 1 year or longer. In a more recent study46 evaluating topical PDT in cats with facial SCC, 85% achieved a complete response.

Unfortunately, 63% of these cats developed recurrence in a median time of 21 weeks. The results of these studies suggest that PDT may be an effective local treatment modality, but PDT is not readily available in private practice.

QuickNotes Surgical excision is the treatment of choice for SCC, but a variety of local and systemic treatment modalities are available to treat tumors that cannot be completely excised.

COX-2 Inhibitors

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In addition to their antiinflammatory effects, COX-2 Mandibular gingival SCC in a dog. inhibitors may have antitumor properties. The use A of piroxicam, a nonspecific COX inhibitor, given alone or in combination with other therapies has been evaluated in dogs with SCC.59–62 Schmidt and colleagues 60 prospectively evaluated the efficacy of daily oral piroxicam in 17 dogs with measurable oral SCC. Three dogs obtained partial or complete remission for a median of 180 days; five other dogs had stable B disease for a median of 102 days. A recent pharmacokinetic study evaluating piroxicam in cats with carcinoma suggested that a dose of 0.3 mg/kg/day PO would be appropriate for clinical trial use in cats with COX-2–positive oral SCC.58 Although these studies have shown only minimal toxicity (mild vomiting or diarrhea in a (A) Before radiation therapy. (B) Two few animals), it should be months after radiation therapy. noted that, as a nonspecific COX inhibitor, piroxicam can induce serious side effects, including gastrointestinal ulceration and renal failure.

COX-2–selective inhibitors have a lower incidence of these side effects, but, as yet, there are no studies evaluating their effect on SCC.

Courtesy of Dr. Kosarek

FIGURE 11

Novel and Multimodality Therapies

liver enzymes and neutropenia in one cat).

Retinoids (vitamin A derivatives) have been evaluated for the treatment of solar-induced SCC and its associated preneoplastic lesions (solar keratosis). In a study assessing the efficacy of etretinate for dogs with solar-induced preneoplastic lesions, five of 10 dogs showed a partial or complete response.65 However, therapeutic efficacy of 13-cis-retinoic acid was not evident in 10 cats with preneoplastic lesions or SCC of the head.66 A multimodal approach to treating dogs and cats with SCC may provide the most therapeutic benefit when surgery cannot be curative. The efficacy of a combination of surgery, carboplatin, and RT was reported in five dogs with tonsillar SCC: the mean survival time was 211 days.67 In an earlier study, five of six dogs with tonsillar SCC treated with a combination of surgery, doxorubicin, cisplatin, and RT had a complete response with a median disease-free interval of 240 days.12 Carboplatin combined with RT has also been employed for treatment of nasal planum SCC in cats with a good response (six of six cats had a complete response and no recurrence for up to 268 days).68 Further prospective studies evaluating multimodal therapy are warranted.

Conclusion SCCs are common tumors of dogs and cats.

They vary in appearance, location, and biologic behavior; however, they are typically locally aggressive, with a reported low to moderate metastatic potential. Early recognition, diagnosis, and treatment are essential. Diagnosis of SCC relies on cytologic or histologic examination of the tumor. Many treatment modalities are available, with surgical excision being the mainstay of therapy. The prognosis for patients with SCC varies. A favorable prognosis exists for patients with well-differentiated tumors that can be completely excised and without evidence of vascular or lymphatic invasion or distant metastases.

Conversely, the prognosis is poor for patients with inoperable or poorly differentiated tumors or with metastatic disease. Further investigation into the tumorigenesis of SCC is warranted.

The findings of these studies may lead to additional preventive measures and novel treatment modalities that improve outcomes for dogs and cats with this type of cancer.

Immunotherapy, the stimulation of the immune system to “reject” a tumor, has been employed in human medicine for treating a variety of cancers, including SCC. Experience with this therapy in small animal medicine is limited.

Imiquimod is a topical immunomodulator that induces cytokine production and may induce tumor apoptosis.63 In a small retrospective study64 evaluating the efficacy and toxicity of topical imiquimod in cats with MSCC, treatment appeared effective in all 12 cats and was associated with mild toxicity (local erythema in three Acknowledgment: The authors thank Dr. C. G. Couto cats, partial anorexia in one cat, and increased for his editing assistance.

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59. Knapp DW, Richardson RC, Bottoms GD, et al. Phase I trial of piroxicam in 62 dogs bearing naturally occurring tumors. Cancer Chemother Pharmacol 1992;29(3):214-218.

60. Schmidt BR, Glickman NW, DeNicola DB, et al. Evaluation of piroxicam for the treatment of oral squamous cell carcinoma in dogs. JAVMA 2001;218(11):1783-1786.

61. Boria PA, Murray DJ, Bennett PF, et al. Evaluation of cisplatin combined with piroxicam for the treatment of oral malignant melanoma and oral squamous cell carcinoma in dogs.

JAVMA 2004;224(3):388-394.

62. Langova V, Mutsaers AJ, Phillips B, et al. Treatment of eight dogs with nasal tumors with alternating doses of doxorubicin and carboplatin in conjunction with oral piroxicam. Aust Vet J 2004;82(11):676-680.

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FREE CE Squamous Cell Carcinoma

63. Shon M, Schon MP. The antitumoral mode of action of imiquimod and other imidazoquinolones. Curr Med Chem 2007;14(6):681-687.

64. Gill V, Bergman P, Baer K, et al. Evaluation of imiquimod 5% (Aldara) in cats with multicentric squamous cell carcinoma in situ (MSCCIS). Proc 26th Vet Cancer Soc 2006:18.

65. Marks SL, Song MD, Stannard AA, et al. Clinical evaluation of etretinate for the treatment of canine solar-induced squamous cell carcinoma and preneoplastic lesions. J Am Acad Dermatol 1992;27(1):11-16.

66. Evans AG, Madewell BR, Stannard AL. A trial of 13-cis-retinoic

acid for the treatment of squamous cell carcinoma and preneoplastic lesions of the head in cats. Am J Vet Res 1985;46(12):2553-2557.

67. Murphy S, Hayes A, Adams V, et al. Role of carboplatin in multimodality treatment of canine tonsillar squamous cell carcinoma—a case series of five dogs. J Small Anim Pract 2006;47(4):216-220.

68. De Vos JP, Burm AGO, Focker BP. Results from the treatment of advanced stage squamous cell carcinoma of the nasal planum in cats, using a combination of intralesional carboplatin and superficial radiotherapy: a pilot study. Vet Comp Oncol 2004;2(2):75-81.

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1. The most common sites of SCC in dogs and cats are a. the reproductive and gastrointestinal tracts. b. within the abdominal and thoracic cavities. c. the skin, oral cavity, and digits. d. the urinary bladder and prostate gland.

2. Most cutaneous SCCs in cats occur a. on the head, often involving the pinna, eyelids, and nasal planum. b. on the torso, often along the dorsal midline and at the tail base. c. on the digits. d. in the perianal region.

3. Which statement regarding the growth and spread of SCC is true? a. Most tumors are well circumscribed and encapsulated, with no risk of local spread or distant metastasis. b. Most tumors are locally invasive, and spread to local lymph nodes may occur. c. Most tumors are accompanied by paraneoplastic leukocytosis or hypertrophic osteopathy. d. Most tumors develop rapidly, with distant metastases present upon initial examination.

4. SCC in situ is a. a large, cauliflower-like SCC, often present on the digit of an affected cat. b. a large, intrathoracic SCC resulting from metastasis. c. the scar that remains within the dermis of cats afflicted with an SCC that has spontaneously resolved. d. a premalignant form of SCC in which the dysplastic cells do not cross the epithelial basement membrane.

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5. Which statement regarding solar keratosis is false? a. Solar keratosis always results in widespread, multiple skin lesions in dogs and cats. b. The lesions of solar keratosis range from an erythematous, scaly thickening of the skin to shallow, crusting lesions. c. The lesions of solar keratosis occur on lightly haired, nonpigmented skin and are associated with UV light exposure. d. With time and continued exposure to UV light, solar keratosis lesions may progress to SCC. 6. Which statement regarding the development of cutaneous SCC is false? a. Prolonged exposure to UV light, lack of skin pigment, and a sparse haircoat all contribute to the development of cutaneous SCC. b. The mechanism frequently proposed for cutaneous SCC and its association with UV light involves the tumor suppressor gene p53. c. In SCC, the p53 gene is activated

by UV light, and the protein product signals increased cell cycling and uncontrolled proliferation of neoplastic squamous cells. d. Cells in which the p53 gene is mutated continue replication even if DNA damage is present, leading to mutation accumulation and a greater chance of neoplasia.

7. Asynchronous nuclear and cytoplasmic maturation, which is a common cytologic finding with SCC, is typified by a. large, anucleate cells that are fully keratinized.

Compendium: Continuing Education for Veterinarians® | March 2009 | CompendiumVet.com

b. large, fully keratinized cells with retained large nuclei. c. small, eosinophilic cells with multiple, irregular nuclei. d. small, anucleate cells with granular, eosinophilic cytoplasm and vacuoles.

8. Which statement regarding the appearance of SCC is false? a. Many SCCs are ulcerative lesions. b. Secondary inflammation is often present when an SCC lesion is ulcerated. c. An inflamed SCC can always be easily differentiated from nonneoplastic inflammatory lesions by cytologic examination. d. Histologic examination may be necessary to differentiate inflammatory from neoplastic cutaneous lesions.

9. Which statement regarding treatment of SCC is true? a. The size of the tumor does not affect treatment decisions. b. Surgery is only necessary if primary treatment modalities fail. c. Tumors respond rapidly and completely to chemotherapy. d. RT is most commonly applied to tumors of the nasal planum, nasal cavity, and oral cavity.

10. The prognosis for animals with SCC depends on the a. size of the tumor. b. location of the tumor. c. treatment modalities employed. d. all of the above

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Competitive salary and benefits include 401(k), profit sharing, CE, and insurance. Experience preferred. Send resume to Dr. Karl B. Milliren, 303 National Highway, Thomasville, NC 27360; email tvh303@cs.com; fax 336-475-0140.

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PRACTICES FOR SALE MARYLAND – Single-doctor small animal practice, established 28 years, available for immediate sale or lease. Recently remodeled 2,000–sq. ft. freestanding facility on 1 acre in new town, Columbia, just 1 mile from town center — ideal location for specialty practice.

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TEXAS – For sale: AAHA-accredited small animal and exotics practice specializing in diagnostic medicine and laser surgery, established in 1982. Located in university area of Houston; excellent demographics. Grossed $860,000 in 2008 — great growth potential for 2009. Equipped with computer technology and in-house diagnostic equipment, including ultrasound and digital x-ray. Highly motivated, certified staff; many with college degrees. Interactive, customdesigned website. Business and real estate package; asking $1,599,000 — financing available. Call 713-446-3399 or email vetdoc81@hotmail.com for your appointment.

Index to Advertisers For free information about products advertised in this issue, email the product names to productinfo@compendiumvet.com.

Contact Lisa Siebert to place your ad today.

Call 215-589-9457 or email lsiebert@vetlearn.com.

Company

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Page

Abbott Animal Health ASPCA Animal Poison Control Bayer Animal Health Dristech, LLC Fort Dodge Animal Health Hill’s Pet Nutrition Lloyd, Inc. Nestlé Purina PetCare Northgate Veterinary Supply Novartis Animal Health

SevoFlo Free magnet Drontal Plus Fovea Digital Radiography ProMeris PetFitness VetSync ToxiBan Case in Brief: FortiFlora Glass cage doors and rod gates Interceptor Osteoarthritis Multimodal Case Challenge Call for papers Stem Cell Therapy Pet Portal Service Job marketplace

119, 120 101 (US only) 123, 124 Inside back cover Inside front cover (US only) Inside front cover (Canada only) 109 115 143 103, 104 Back cover 114 107 117 143

Veterinary Therapeutics Vet-Stem, Inc. Vetstreet WhereTechsConnect.com

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New Ad Placement Available Discounts

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*All ads are subject to a 40-word minimum charge and may be edited for grammar and style. All ads are posted on VetClassifieds.com on the first day of the issue month at no charge; all other advertising options incur an additional charge. Discounts are not applicable to first ad placement. Limit one discount per ad, barring promotional specials. All ads received after deadline will be printed in the next available issue(s). No cancellation after deadline. Include complete billing information with all orders. DO NOT mail check or money order payments with your ad; call for detailed instructions first. DO NOT email credit card information; mail or fax your payment information or use our secure Internet server at VetClassifieds.com.

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Visit www.VetClassifieds.com to browse ads or place your order

The Future of Your Practice. The Future of Digital Radiography.

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