Compendium | April 2009 by davidpsu

VOLUME 31 NUMBER 4 APRIL 2009

Compendium CompendiumVet.com | Peer Reviewed | Listed in MEDLINE

6 CE Contact Hours

CONTI N U I NG EDUCATION FOR VETERI NARIANS ®

Refereed Peer Review

Intracranial Arachnoid Cysts Imaging and Diagnosis

PAGES 145–200

Focus on Nutrition Antioxidants in Cancer Treatment FREE

Pancarpal and Partial Carpal Arthrodesis

Surgical Views Laparoscopic Biopsy Techniques

fo te C rS d m # om al 1 lA i pe ni n m O nd al v Ve e ium te ra rin l ar l Q yJ u ou a rn lit al y s! *

COMPENDIUM CONTINUING EDUCATION FOR VETERINARIANS®

FREE

Vol 31(4) April 2009

Hill's_Canada_USE.qxp:1

2/26/09

3:27 PM

Page 1

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VetSync is an ongoing program. Hill’s has the right to change this program any time.

April 2009 Vol 31(4) 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. Subscription rate: $79 for 1 year; $143 for 2 years; $217 for 3 years. Canadian and Mexican subscriptions (surface mail): $95 for 1 year; $169 for 2 years; $270 for 3 years. Foreign subscriptions (surface mail): $175 for 1 year; $275 for 2 years; $425 for 3 years. Payments by check must be in U.S. funds drawn on a U.S. branch of a U.S. bank only; credit cards are also accepted. Change of Address: Please notify the Circulation Department 45 days before the change is to be effective. Send your new address and enclose an address label from a recent issue. Selected back issues are available for $15 (United States and Canada) and $17 (foreign) each (plus postage). Indexing: Compendium: Continuing Education for Veterinarians® is included in the international indexing coverage of Current Contents/ Agriculture, Biology and Environmental Sciences (ISI); SciSearch (ISI); Research Alert (ISI); Focus On: Veterinary Science and Medicine (ISI); Index Veterinarius (CAB International, CAB Abstracts, CAB Health); and Agricola (Library of Congress). Article retrieval systems include The Genuine Article (ISI), The Copyright Clearance Center, Inc., University Microfilms International, and Source One (Knight-Ridder Information, Inc.). Yearly author and subject indexes for Compendium are published each December.

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145

April 2009 Vol 31(4) 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

146

CompendiumVet.com com

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, Oncology), DECVIM-CA (Oncology) CVS Angel Care Cancer Center and Special Care Foundation for Companion Animals Carlsbad, 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 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.

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

April 2009 Vol 31(4)

Features 154 Focus on Nutrition

CompendiumVet.com | Peer Reviewed | Listed in MEDLINE

Antioxidants in Cancer Treatment: Helpful or Harmful? ❯❯ Lisa M. Freeman Cancer patients often receive dietary supplements, but not all owners mention supplements in the dietary history. Veterinarians need to be aware of how supplements can interact with other therapies.

160

Intracranial Arachnoid Cysts in Dogs ❯❯ Curtis W. Dewey, Peter V. Scrivani, Ursula Krotscheck, Soﬁa Cerda-Gonzalez, Kerry Smith Bailey, and Dominic J. Marino FREE

170 Surgical Views Techniques for Laparoscopic and LaparoscopicAssisted Biopsy of Abdominal Organs ❯❯ Philipp Mayhew Read an overview of laparoscopic techniques for harvesting biopsy samples from the liver, kidneys, gastrointestinal tract, and pancreas. Several videos demonstrating aspects of these techniques are available online.

180 FREE

Pancarpal and Partial Carpal Arthrodesis ❯❯ Nicole J. Buote, Daryl McDonald, and Robert Radasch Partial carpal and pancarpal arthrodesis may involve surgical implantation of plates and pins or the use of external ﬁxation devices. The techniques for each approach and their associated complications are discussed.

193 Case Report Ovarian Teratoma in a Mediterranean Tortoise ❯❯ Jaime Martorell, Sara Soto, Sara Barrera, and Antonio Ramis The authors present the ﬁrst reported case of a teratoma in tortoise gonadal tissue.

On the Cover Dr. Curtis Dewey, chief of the neurology section at the Cornell University Hospital for Animals, and resident David Brewer examine magnetic resonance imaging studies for evidence of an intracranial arachnoid cyst (IAC). Shih tzus are most likely to be affected by these cysts. In the article beginning on page 160, Dr. Dewey presents information on the imaging and diagnosis of IACs.

Departments 148 The Editor’s Desk: When You Find a Keeper… ❯❯ Tracey L. Giannouris

Acey visits Dr. Fuerst PAGE 148

152 Reading Room: A Practical Guide to Canine and Feline Neurology

198 Index to Advertisers

153 CompendiumVet.com

198 Market Showcase

197 Product Forum

198 Classiﬁed Advertising

2009 PERQ/HCI FOCUS® Veterinary Study of Total Companion Animal Veterinarians, in comparison to ratings for each publication, by that publication’s readers. Compendium: Continuing Education for Veterinarians®

147

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

Tracey with her son, Michael Francis

When You Find a Keeper…

’m sure you can relate to that sinking feeling offices here in Yardley, Pennsylvania, to pick up you experience when you desperately scan Acey, and you’re talking about a solid 70-mile your new health insurance carrier’s “in-net- trip…one way. Nevertheless, it never crossed our work” list and learn that your trusted physician minds to take him somewhere closer to our new of the past 10-plus years does not participate in neck of the woods. that particular plan. And even when your health Dr. Fuerst has ministered to all of Acey’s health care provider is in the network, sometimes cir- care needs, ranging from clearing up a frustratcumstances such as moving to an area farther ing and refractory ear infection to removing a from your physician’s practice can be a source neural sheath tumor to performing regular physiof angst (“Now what do I do?”). For my husband cal examinations and vaccinations. Through the and me, this decision was pretty easy after we years, he’s come to know not only Acey’s physimoved from Middlesex County, New Jersey, far- cal condition and history but also his temperather west to Hunterdon County: we would just ment and behavior (meaning he knows what a make the longer “schlep” to keep visiting our big chicken our little old man is and how to put familiar physicians. him at ease). It was likewise a no-brainer for us when it came Because of our respective work schedules, to the veterinary care of our 12½-year-old German my husband and I usually can only take Acey shorthaired pointer, Acey: we would continue to to office visits in the late afternoon or early evedrive him to see David Fuerst, DVM, to whom ning. Those of you familiar with the parking lot we have entrusted his health care for the past 6 that most New Jersey highways resemble during years. Bear in mind, Dr. Fuerst and the other fine the evening rush hour can understand the issues veterinary practitioners at Boulevard Veterinary involved in getting Acey to his appointments on Clinic in Kenilworth, New Jersey, are a good 44+ time. Despite the best-laid plans and extra time miles from our home in Flemington; add an extra allowed, we often find ourselves sitting on Route 24 miles for the trip home from the Compendium 287 or 22, staring at the clock and worrying that we’ll never make it. More than once, we’ve had to make an apologetic phone call to give the clinic a Tracey, Dr. Fuerst, and heads-up that we are running late and will underAcey in the exam room. stand if the doctor would prefer that we reschedule. On each of these occasions, however, either the receptionist or Dr. Fuerst himself has picked up the phone, asked how Acey was doing, and reassured us that they’ll be there waiting for us. Even though we’re usually the last appointment of the day, Dr. Fuerst and the veterinary staff always greet us with genuine and welcoming smiles. Regardless of the hour, Dr. Fuerst and his team of technicians always take the time to carefully review Acey’s history and any current signs before the examination. In addition to the thorough knowledge, close follow-up, and care that he and his staff provide, Dr. Fuerst also takes time to “talk” with Acey, petting him and reas-

148

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

The secret to a longer life in dogs with heart failure.

The QUEST study provides new evidence that Vetmedin® (pimobendan) extends life for dogs with congestive heart failure (CHF). In a study of unprecedented magnitude, dogs with CHF due to mitral valve disease who were treated with VETMEDIN* lived virtually twice as long as those on an ACE inhibitor.1 This hard evidence from the QUEST study supports using VETMEDIN as ﬁrst-line therapy in all dogs with symptomatic CHF. News like this should make your clients jump for joy as well. *The study used VETMEDIN Capsules. In the US, only chewable tablets are licensed. Both capsules and chewable tablets contain the same pharmaceutical ingredient, pimobendan, and are considered equivalent for clinical use. Bioequivalence, however, has not been established. Visit www.questtrial.com for additional study details, and visit www.vetmedin-us.com for more information about VETMEDIN.

Important safety information: VETMEDIN should not be given in case of hypertrophic cardiomyopathy, aortic stenosis, or any other clinical condition where an augmentation of cardiac output is inappropriate for functional or anatomical reasons. The safety of VETMEDIN has not been established in dogs with asymptomatic heart disease or in heart failure caused by other etiologies other than atrioventricular valvular insufﬁciency or dilated cardiomyopathy. Use only in dogs with clinical evidence of heart failure. The most common side effects reported in ﬁeld studies were poor appetite, lethargy, diarrhea, dyspnea, azotemia, weakness, and ataxia. If side effects should occur, pet owners should contact their veterinarian. Please refer to the package insert for complete product information or visit www.vetmedin-us.com. Reference: 1. Häggström J et al. Effect of pimobendan or benazepril hydrochloride on survival times in dogs with congestive heart failure caused by naturally occurring myxomatous mitral valve disease: The QUEST study. J Vet Intern Med. 2008;22:1124–1135.

See Page 150 for Product Information Summary

higher in the active control group (4%) compared to the Vetmedin group (1%).

NADA 141-273, Approved by FDA

Vetmedin

(pimobendan) Chewable Tablets Cardiac drug for oral use in dogs only Caution: Federal law restricts this drug to use by or on the order of a licensed veterinarian. Description: Vetmedin (pimobendan) is supplied as oblong half-scored chewable tablets containing 1.25, 2.5 or 5 mg pimobendan per tablet. Pimobendan, a benzimidazole-pyridazinone derivative, is a nonsympathomimetic, non-glycoside inotropic drug with vasodilatative properties. Pimobendan exerts a stimulatory myocardial effect by a dual mechanism of action consisting of an increase in calcium sensitivity of cardiac myofilaments and inhibition of phosphodiesterase (Type III). Pimobendan exhibits vasodilating activity by inhibiting phosphodiesterase III activity. The chemical name of pimobendan is 4,5-dihydro-6-[2-(4-methoxyphenyl)-1Hbenzimidazole-5-yl]-5-methyl-3(2H)-pyridazinone. The structural formula of pimobendan is:

Adverse reactions/new clinical findings were seen in both treatment groups and were potentially related to CHF, the therapy of CHF, or both. The following adverse reactions/new clinical findings are listed according to body system and are not in order of prevalence: CHF death, sudden death, chordae tendineae rupture, left atrial tear, arrhythmias overall, tachycardia, syncope, weak pulses, irregular pulses, increased pulmonary edema, dyspnea, increased respiratory rate, coughing, gagging, pleural effusion, ascites, hepatic congestion, decreased appetite, vomiting, diarrhea, melena, weight loss, lethargy, depression, weakness, collapse, shaking, trembling, ataxia, seizures, restlessness, agitation, pruritus, increased water consumption, increased urination, urinary accidents, azotemia, dehydration, abnormal serum electrolyte, protein, and glucose values, mild increases in serum hepatic enzyme levels, and mildly decreased platelet counts. See Table 1 for mortality due to CHF (including euthanasia, natural death, and sudden death) and for the development of new arrhythmias (not present in a dog prior to beginning study treatments) by treatment group and type of heart disease (AVVI or DCM) in the 56-day field study. Table 1: CHF Death and New Arrhythmias in the 56-Day Field Study

Indications: Vetmedin (pimobendan) is indicated for the management of the signs of mild, moderate, or severe (modified NYHA Class IIa, IIIb, or IV c) congestive heart failure in dogs due to atrioventricular valvular insufficiency (AVVI) or dilated cardiomyopathy (DCM). Vetmedin is indicated for use with concurrent therapy for congestive heart failure (e.g., furosemide, etc.) as appropriate on a case-by-case basis. a

Dogs that died due to CHF

A dog with modified New York Heart Association (NYHA) Class II heart failure has fatigue, shortness of breath, coughing, etc. apparent when ordinary exercise is exceeded.

A dog with modified NYHA Class III heart failure is comfortable at rest, but exercise capacity is minimal.

A dog with modified NYHA Class IV heart failure has no capacity for exercise and disabling clinical signs are present even at rest.

Dosage and Administration: Vetmedin should be administered orally at a total daily dose of 0.23 mg/lb (0.5 mg/kg) body weight, using a suitable combination of whole or half tablets. The total daily dose should be divided into 2 portions that are not necessarily equal, and the portions should be administered approximately 12 hours apart (i.e., morning and evening). The tablets are scored and the calculated dosage should be provided to the nearest half tablet increment. Contraindications: Vetmedin should not be given in cases of hypertrophic cardiomyopathy, aortic stenosis, or any other clinical condition where an augmentation of cardiac output is inappropriate for functional or anatomical reasons. Warnings: Only for use in dogs with clinical evidence of heart failure. At 3 and 5 times the recommended dosage, administered over a 6-month period of time, pimobendan caused an exaggerated hemodynamic response in the normal dog heart, which was associated with cardiac pathology (See Animal Safety). Human Warnings: Not for use in humans. Keep this and all medications out of reach of children. Consult a physician in case of accidental ingestion by humans. Precautions: The safety of Vetmedin has not been established in dogs with asymptomatic heart disease or in heart failure caused by etiologies other than AVVI or DCM. The safe use of Vetmedin has not been evaluated in dogs younger than 6 months of age, dogs with congenital heart defects, dogs with diabetes mellitus or other serious metabolic diseases, dogs used for breeding, or pregnant or lactating bitches. Adverse Reactions: Clinical findings/adverse reactions were recorded in a 56-day field study of dogs with congestive heart failure (CHF) due to AVVI (256 dogs) or DCM (99 dogs). Dogs were treated with either Vetmedin (175 dogs) or the active control enalapril maleate (180 dogs). Dogs in both treatment groups received additional background cardiac therapy (See Effectiveness for details and the difference in digoxin administration between treatment groups). The Vetmedin group had the following prevalence (percent of dogs with at least one occurrence) of common adverse reactions/new clinical findings (not present in a dog prior to beginning study treatments): poor appetite (38%), lethargy (33%), diarrhea (30%), dyspnea (29%), azotemia (14%), weakness and ataxia (13%), pleural effusion (10%), syncope (9%), cough (7%), sudden death (6%), ascites (6%), and heart murmur (3%). Prevalence was similar in the active control group. The prevalence of renal failure was

Dogs that developed new arrhythmiasa

Vetmedin® Group

Active Control Group

14.3% n=175

14.4% n=180

9 of 126 dogs with AVVI

16 of 130 dogs with AVVI

16 of 49 dogs with DCM

10 of 50 dogs with DCM

39.4% n=175

45.0% n=180

45 of 126 dogs with AVVI

59 of 130 dogs with AVVI

24 of 49 dogs with DCM

22 of 50 dogs with DCM

New arrhythmias included supraventricular premature beats and tachycardia, atrial fibrillation, atrioventricular block, sinus bradycardia, ventricular premature beats and tachycardia, and bundle branch block

Following the 56-day masked field study, 137 dogs in the Vetmedin group were allowed to continue on Vetmedin in an open-label extended-use study without restrictions on concurrent therapy. The adverse reactions/new clinical findings in the extended-use study were consistent with those reported in the 56-day study, with the following exception: One dog in the extended-use study developed acute cholestatic liver failure after 140 days on Vetmedin and furosemide. In foreign post-approval drug experience reporting, the following additional suspected adverse reactions were reported in dogs treated with a capsule formulation of pimobendan: hemorrhage, petechia, anemia, hyperactivity, excited behavior, erythema, rash, drooling, constipation, and diabetes mellitus. To report suspected adverse reactions, to obtain a Material Safety Data Sheet, or for technical assistance call 1-866-638-2226. Clinical Pharmacology: Pimobendan is oxidatively demethylated to a pharmacologically active metabolite which is then conjugated with sulfate or glucuronic acid and excreted mainly via feces. The mean extent of protein binding of pimobendan and the active metabolite in dog plasma is >90%. Following a single oral administration of 0.25 mg/kg Vetmedin tablets the maximal mean (± 1 SD) plasma concentrations (Cmax) of pimobendan and the active metabolite were 3.09 (0.76) ng/mL and 3.66 (1.21) ng/mL, respectively. Individual dog Cmax values for pimobendan and the active metabolite were observed 1 to 4 hours postdose (mean: 2 and 3 hours, respectively). The total body clearance of pimobendan was approximately 90 mL/min/kg, and the terminal elimination half-lives of pimobendan and the active metabolite were approximately 0.5 hours and 2 hours, respectively. Plasma levels of pimobendan and active metabolite were below quantifiable levels by 4 and 8 hours after oral administration, respectively. The steady-state volume of distribution of pimobendan is 2.6 L/kg indicating that the drug is readily distributed into tissues. Food decreased the bioavailability of an aqueous solution of pimobendan, but the effect of food on the absorption of pimobendan from Vetmedin tablets is unknown. In normal dogs instrumented with left ventricular (LV) pressure transducers, pimobendan increased LV dP/dtmax (a measure of contractility of the heart) in a dose dependent manner between 0.1 and 0.5

mg/kg orally. The effect was still present 8 hours after dosing. There was a delay between peak blood levels of pimobendan and active metabolite and the maximum physiologic response (peak LV dP/dtmax). Blood levels of pimobendan and active metabolite began to drop before maximum contractility was seen. Repeated oral administration of pimobendan did not result in evidence of tachyphylaxis (decreased positive inotropic effect) or drug accumulation (increased positive inotropic effect). Laboratory studies indicate that the positive inotropic effect of pimobendan may be attenuated by the concurrent use of a ß-adrenergic blocker or a calcium channel blocker.

the average voluntary consumption was 84.2%.

Effectiveness: In a double-masked, multi-site, 56-day field study, 355 dogs with modified NYHA Class II, III, or IV CHF due to AVVI or DCM were randomly assigned to either the active control (enalapril maleate) or the Vetmedin (pimobendan) treatment group. Of the 355 dogs, 52% were male and 48% were female; 72% were diagnosed with AVVI and 28% were diagnosed with DCM; 34% had Class II, 47% had Class III, and 19% had Class IV CHF. Dogs ranged in age and weight from 1 to 17 years and 3.3 to 191 lb, respectively. The most common breeds were mixed breed, Doberman Pinscher, Cocker Spaniel, Miniature/Toy Poodle, Maltese, Chihuahua, Miniature Schnauzer, Dachshund, and Cavalier King Charles Spaniel. The 180 dogs (130 AVVI, 50 DCM) in the active control group received enalapril maleate (0.5 mg/kg once or twice daily), and all but 2 received furosemide. Per protocol, all dogs with DCM in the active control group received digoxin. The 175 dogs (126 AVVI, 49 DCM) in the Vetmedin group received pimobendan (0.5 mg/kg/day divided into 2 portions that were not necessarily equal, and the portions were administered approximately 12 hours apart), and all but 4 received furosemide. Digoxin was optional for treating supraventricular tachyarrhythmia in either treatment group, as was the addition of a ß-adrenergic blocker if digoxin was ineffective in controlling heart rate. After initial treatment at the clinic on Day 1, dog owners were to administer the assigned product and concurrent medications for up to 56±4 days.

Table 3: Incidence of Cardiac Pathology/ Histopathology in the Six-month Safety Study

The determination of effectiveness (treatment success) for each case was based on improvement in at least 2 of the 3 following primary variables: modified NYHA classification, pulmonary edema score by a masked veterinary radiologist, and the investigator’s overall clinical effectiveness score (based on physical examination, radiography, electrocardiography, and clinical pathology). Attitude, pleural effusion, coughing, activity level, furosemide dosage change, cardiac size, body weight, survival, and owner observations were secondary evaluations contributing information supportive to product effectiveness and safety. Based on protocol compliance and individual case integrity, 265 cases (134 Vetmedin, 131 active control) were evaluated for treatment success on Day 29. See Table 2 for effectiveness results. Table 2: Effectiveness Results for the 56-Day Field Study

Treatment Success on Day 29

Treatment Success on Day 56

No increase in furosemide dose between Day 1 and Day 29

Vetmedin® Group

Active Control Group

80.7% n=134

76.3% n=131

88 of 101 dogs with AVVI

77 of 100 dogs with AVVI

20 of 33 dogs with DCM

23 of 31 dogs with DCM

71.1% n=113

67.2% n=110

66 of 85 dogs with AVVI

56 of 85 dogs with AVVI

13 of 28 dogs with DCM

17 of 25 dogs with DCM

78.3% n=130

68.6% n=126

Animal Safety: In a laboratory study, Vetmedin chewable tablets were administered to 6 healthy Beagles per treatment group at 0 (control), 1, 3, and 5 times the recommended dosage for 6 months. See Table 3 for cardiac pathology results. The cardiac pathology/histopathology noted in the 3X and 5X dose groups is typical of positive inotropic and vasodilator drug toxicity in normal dog hearts, and is associated with exaggerated hemodynamic responses to these drugs. None of the dogs developed signs of heart failure and there was no mortality.

Severe left ventricular hypertrophy with multifocal subendocardial ischemic lesions

One 3X and two 5X dogsa

Moderate to marked myxomatous thickening of the mitral valves

Three 5X dogs

Myxomatous thickening of the chordae tendineae

One 3X and two 5X dogs

Endocardial thickening of the left ventricular outflow tract

One 1X, two 3X, and two 5X dogs

Left atrial endocardial thickening (jet lesions) in 2 of the dogs that developed murmurs of mitral valve insufficiency

One 3X and one 5X dog

Granulomatous inflammatory lesion in the right atrial myocardium

One 3X dog

Most of the gross and histopathologic findings occurred in these three dogs

Murmurs of mitral valve insufficiency were detected in one 3X (Day 65) and two 5X dogs (Days 135 and 163). These murmurs (grades II-III of VI) were not associated with clinical signs. Indirect blood pressure was unaffected by Vetmedin at the label dose (1X). Mean diastolic blood pressure was decreased in the 3X group (74 mmHg) compared to the control group (82 mmHg). Mean systolic blood pressure was decreased in the 5X group (117 mmHg) compared to the control group (124 mmHg). None of the dogs had clinical signs of hypotension. On 24-hour Holter monitoring, mean heart rate was increased in the 5X group (101 beats/min) compared to the control group (94 beats/min). Not counting escape beats, the 3X and 5X groups had slightly higher numbers of isolated ventricular ectopic complexes (VEs). The maximum number of nonescape VEs recorded either at baseline or in a control group dog was 4 VEs/24 hours. At either Week 4 or Week 20, three 3X group dogs had maximums of 33, 13, and 10 VEs/24 hours, and two 5X group dogs had maximums of 22 and 9 VEs/24 hours. One 1X group dog with no VEs at baseline had 6 VEs/24 hours at Week 4 and again at Week 20. Second-degree atrioventricular heart block was recorded in one 3X group dog at Weeks 4 and 20, and in one dog from each of the 1X and 5X groups at Week 20. None of the dogs had clinical signs associated with these electrocardiogram changes. Treatment was associated with small differences in mean platelet counts (decreased in the 3X and 1X groups), potassium (increased in the 5X group), glucose (decreased in the 1X and 3X groups), and maximum blood glucose in glucose curves (increased in the 5X group). All individual values for these variables were within the normal range. Three 1X and one 5X group dogs had mild elevations of alkaline phosphatase (less than two times normal). Loose stools and vomiting were infrequent and self-limiting. Storage Information: Store at controlled room temperature 59-86°F (15-30°C).

At the end of the 56-day study, dogs in the Vetmedin group were enrolled in an unmasked field study to monitor safety under extended use, without restrictions on concurrent medications. Vetmedin was used safely in dogs concurrently receiving furosemide, digoxin, enalapril, atenolol, spironolactone, nitroglycerin, hydralazine, diltiazem, antiparasitic products (including heartworm prevention), antibiotics (metronidazole, cephalexin, amoxicillin-clavulanate, fluoroquinolones), topical ophthalmic and otic products, famotidine, theophylline, levothyroxine sodium, diphenhydramine, hydrocodone, metoclopramide, and butorphanol, and in dogs on sodium-restricted diets. Palatability: In a laboratory study, the palatability of Vetmedin was evaluated in 20 adult female Beagle dogs offered doses twice daily for 14 days. Ninety percent (18 of 20 dogs) voluntarily consumed more than 70% of the 28 tablets offered. Including two dogs that consumed only 4 and 7% of the tablets offered,

How Supplied: Vetmedin® (pimobendan) Chewable Tablets: Available at 1.25, 2.5 or 5 mg oblong half-scored chewable tablets – 50 tablets per bottle. Manufactured by: MEDA Manufacturing GmbH Cologne, Germany Manufactured for: Boehringer Ingelheim Vetmedica, Inc. St. Joseph, MO 64506 U.S.A. 1-866-638-2226 VETMEDIN is a registered trademark of Boehringer Ingelheim Vetmedica GmbH, licensed to Boehringer Ingelheim Vetmedica, Inc. © 2009 Boehringer Ingelheim Vetmedica, Inc. Code 448011, 448111, 448211 Revised 06/2007

The Editor’s Desk suring him with the smile and gentle touch that mark a veterinarian as someone who is true to his calling. As practitioners, you know that this bond of trust and confidence doesn’t happen overnight, but rather is cultivated over time by nurturing a relationship with both clients and patients. That’s why, despite the distance, inclement weather, and inevitable traffic delays, we’ll continue to take Acey to see Dr. Fuerst. It’s the accumulated years of confidence and trust in his care that make the long haul worth it, each and every time. When you find a “keeper,” you’ll return again and again, no matter the inconvenience. To

Dr. Fuerst and all of the excellent, dedicated veterinarians out there, the entire team here at Compendium says “thank you” for providing such reliable, high-quality care to our pets.

Looking for new team members? Reach over 56,800 total qualiﬁed subscribers1 — plus the virtually unlimited Internet audience — with your classiﬁed ad in COMPENDIUM.

SHARE YOUR COMMENTS As always, we welcome your feedback, comments, and suggestions. Please feel free to e-mail me at tgiannouris@vetlearn.com.

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❯❯ Pneumothorax ❯❯ Arterial and Venous Blood Gases: Indications, Interpretations, and Clinical Applications

Canadian News Ontario Veterinary College Helps Keep Clinics Clean T

he Ontario Veterinary College at the University of Guelph has released a new online handbook, Infection Prevention and Control: Best Practices for Small Animal Veterinary Clinics, designed to help veterinarians stem the spread of disease. The handbook details basic practices of cleanliness and shows how to create an infection control program. The manual was written by Drs. Scott Weese and John Prescott, patho-

biology professors at the University of Guelph, along with postdoctoral student Maureen Anderson and secondyear DVM student Jenny Montgomery. Running 70 pages, the new handbook, possibly the ﬁrst of its kind for veterinary medicine, is available online at www.wormsandgermsblog.com, a joint venture of the Ontario Veterinary College’s Centre for Public Health and Zoonoses and the City of Hamilton Public Health Department.

Yukon Creates Animal Health Program

he Yukon government has pledged $320,000, subject to legislative approval, for the creation of a new animal health program for the territory. The funds will cover the costs of hiring a chief veterinary ofﬁcer and support staff. The staff will provide oversight and veterinary services to the govern-

ment’s various animal health and protection initiatives. The program “will help us keep our wild and domestic animal populations healthy and viable, which in turn will benefit all Yukoners,” Environment Mini ster Elaine Taylor said in a release.

Quebec Creates Group to Study Breeder Regulations

he government of Quebec is considering new regulations on dog breeders conducting business in the province. A new committee formed by the agriculture ministry will study the state of pet welfare in the province and make long- and short-term recommendations, which may include mandatory registration. This action comes in the wake of a series of puppy-mill busts that occurred during the most recent election season, as well as a petition sent to the government. In addition to registration rules, animal rights activists are pushing for more funding for animal rights groups, increased enforcement—the current governing body, ANIMA-Québec, only has ﬁve inspectors—and stronger penalties for puppy mill owners and those violating animal rights.

Coming Events May 12 Toronto Academy of Veterinary Medicine: Problems of the Senior Pet: What Needs to Be Treated and What Can Be Ignored Dave & Buster’s Toronto, Ontario This case-based talk, presented by Dr. Doreen Houston, will focus on the aging process in dogs and cats and will offer 5.5 CE credits. Phone 800-670-1702 Web tavm.org

June 6 Lifelearn Inc. Continuing Education: Cruciate Surgery Ontario Veterinary College University of Guelph, Ontario This 1-day course, presented by Dr. Noel Moens and Dr. Tom Gibson, will focus on surgical repair of cranial cruciate ligament ruptures. The course will consist of morning lectures followed by a lab. Phone 800-375-7994 | Web lifelearn.com

May 13 Calgary Academy of Veterinary Medicine: Nutrition in Critical Illness Clara Christie Theatre, Health Sciences University of Calgary, Alberta This seminar offers 1.5 hours of scientiﬁc CE and will be presented by Dr. Glenna Mauldin. Phone 403-863-7160 Email info@cavm.ab.ca Web cavm.ab.ca/ce_calendar.html

June 18–20 Saskatchewan Veterinary Medical Association: June Conference Delta Regina Hotel Regina, Saskatchewan This 3-day conference will include presentations on both large and companion animal topics. Presentations will be made on cardiology, drug management, feline dentistry, and the future of veterinary medicine. A wet lab on hoof care will also be offered. Phone 306-955-7862 | Web svma.sk.ca

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

September 9 Calgary Academy of Veterinary Medicine: Ophthalmology Clara Christie Theatre, Health Sciences University of Calgary, Alberta This seminar offers 1.5 hours of scientiﬁc CE and will be presented by Dr. Cheryl Cullen. Phone 403-863-7160 Email info@cavm.ab.ca Web cavm.ab.ca/ce_calendar.html September 15 Totonto Academy of Veterinary Medicine: Update on Clinical Gastroenterology Dave & Buster’s Toronto, Ontario This seminar will provide an update on gastrointestinal disorders of cats and dogs, with an emphasis on diagnosis and treatment. It will offer 5.5 CE credits. Phone 800-670-1702 Web tavm.org

April 2009 Vol 31(4)

WEB EXCLUSIVES

CE ARTICLES

❯❯ A Comparative Review of Intracranial Meningioma in Dogs and Cats ❯❯ Kara Sessums and Christopher Mariani Meningiomas are extraaxial tumors that arise from the arachnoid layer of the meninges. Seizures are the most common clinical sign in dogs; cats more often present with mentation changes, vision loss, and gait abnormalities. Meningiomas in both species typically have an insidious onset of clinical signs due to their slow growth. Therapy can target the primary tumor with surgery, radiation, and chemotherapy but may be conﬁned to treating its secondary effects.

❯❯ Acute Salt Toxicity ❯❯ Catherine M. Kasai and Robert King Salt toxicity can be fatal in dogs and cats. Whether toxicity occurs accidentally or iatrogenically, it is important to recognize the clinical signs of sodium toxicosis. Clinical signs are mainly caused by hypernatremia and associated cerebral edema. Treatment involves prompt initiation of ﬂuid therapy along with careful monitoring of neurologic status, serum and plasma electrolytes, and serum osmolarity.

HANDOUTS

❯❯ Focus on Nutrition: Sample Diet History Form This downloadable form can be given to clients to gather important information about their pet’s diet.

DIET HISTO

Date: __________ RY FORM __________ __________ Case Number: __________ Behavior _______ DIET HIS __________ __________ __________ TORY What is__________ Owner Information FORM your pet’s attitude toward P Greed Name: __________ food? P Indifference __________ Table foods __________ Has your Email address: or scaps; __________ P Avoidance pet’s __________ attitude _______ home-p ______ __________ toward ______ repared ______ Phone (home): __________ food change ______ foodss ______ __________ __________ ______ d? If so, ______ __________ ______ ______ ______ describe: ______ Phone (cell): __________ ______ ______ ______ ___________ ______ __________ __________ ______ ______ ______ ______ __________ ______ ______ ______ ______ ______ ______ __________ Best time to ______ ______ ______ ______ ____ ______ __________ call:________________ ___________ ______ ____ ______ ______ ______ __ ______ ______ ______ ______ ______ __________ ______ ______ ______ ______ ______ ______ __________ ______ ___ ____ ___________ ______ ____ ______ ______ ______ Pet Information ______ ______ ______ ______ _ ______ ______ If you have ______ ______ ______ ______ ____ ______ ____ other pets, ______ ______ ______ Name: __________ ______ ______ ______ is this pet ________ Dietary P P Dom ______ __________ ______ Domina supplem domina ____ inant ____ __________ ____________ nt P Subm ents; food Species: __________ nt or submis ____ _______ Age: ______ Has your ________ Is used to ______ food left out issive __________ ______ to give pills ____ for your petsive pet recently _ Breed: __________ Gender: P Male ______ duringthem? the day? ______ ______ _________lost orDoes ______ P Female P Yes______ your pet have gained ______ ______ P No Neutered/spayed: weight? access to other, ____________ Current weight: ______ ______ _________ unmonitored P Yes ______ ______ (e.g., treats If so, please __________ ______ ______ P ______ No food ______ ______ ___ Usual sources ______ ______ fed by neighbor,describe: ____ Body condition ____________ ______ weight: __________ ______ ______ food ______ _ score (1–9): ______ ______ ______ cats)? _______________ P Yes P No ____________ left for outdoor ___ ______ _____ ______ ______ ______ ____ ____ Evidence of muscle ______ ______ ______ ______ ______ _______ ______ If yes, please ____________ wasting P ______ ______ ______ __ ______ ______ None P______ ______ describe:__ ______ ____ ____ Mild P ______ ______ ______ ______ ______ __________ List ______ _______ __________ ______ ______ Have there Severe Reason for Visit ______ __ ____ ______ ____________________ __________ anythin__________ ______ been any __________ ______ g else given ______ ______ __________ recent change ______ _______ __________ ______ _____________ ______ __________ by mouth ______ ____________________ ___ ____ ______ ______ s in activity __________ (e.g., medica __ __________ ______ ______ ________________ __________ level? ______ ations): __________________________ tions): t __________ __________ ______ __________ ____________ ______ __________ ______ _________ ______ ____ __________ ______ __________ ______ ______ ________ __________ ______ __________ ______ _______ __________ ______ __________ ________________ ______ ________________________ ______ __________ ______ ______ __________ ____ ____ ______ ______ ____ __________ ______ __________ ________ ______ ______ __________ __________ you have more____________ ______ _________ Have you __________ ______If______ ______ ______ ____________ ______ ________ ______ observe ____ ______ ______ than one pet, do Household Demograph ______ they have access d any__ ______ ______ food? P Yes ______ __ of the followin _______ ______ ics Nausea/salivat ______ to each other’s ______ P______ _________ ______ No If____ ______ How many adults g: yes, please describe: ______ ion ______ __________ are in your household? Difﬁcul ______ __ _______ ______ __________ ______ _________ ______ __________ ____________ ty chewin How many children __________ ______ __________ __________ ______ g _________ P Yes are in your household, Dyspha ______ ___ __________ _______ ______ Is your ____________ P No ______ __________ ______ __________ and how old _____ giaare pet’s current ____ __________ ______ __________ __________ they? P Yes __________ diet ______ ___ __________ __________ _ Vomitin ______ a P No __ change from P Yes ______ __________g __________ __________ _____ ____ __________ __________ P No __________ __________ P Yes its typical __ __________ __________ P al diet? If so, please____________ Diarrhea __________ __________ __________ No __________ __________ __________ describe __________ P __ __________ __________ the__change Yes P __________ ______ Constip __________ __________ __________ No ______ ation and why __________ __________ __________ How do you P ______ the diet __ __________ Have __________ store Yes ______ ______ your pet’s was change __________ there been __ ______ Where is your P No food? __________ ______ __________ pet housed? d. ______ __________ P any change ______ __ ______ __________ __________ P Indoors Yes P__________ ______ __________ ______ s in urinatio ____ Do you have ______ P Outdoors ______ No ______ ______ other pets? _____ __________ n? ______ __________ P Both ______ P Yes PDiet __________ P Yes ______ __________ __________ ______ ______ No If so, please __ ______ and specify if ______ P__________ No ______ ______ _____ __________ they live indoors list species __________ ______ For each ______ __________ __________ ______ ___________ or outdoors. ______ of __________ __ ______ __________ ____________ ______ cable) and the following categor __________ __________ ______ __________ ______ ____ ______ __________ amounts __________ __________ ______ ___________ ______ __________ __________ often __ ______ ______________________ ______ of all foods ies, list the brand __________ each food __________ ______ __________ ______ ____ __________ ______ __ __________ your names (if __________ ______ ___________ pet eats __________ ______ __________ is fed (e.g., twice __________ appli- Are you open __ ______ Comme __________ ______ daily, as __________ __________ ______ rcial foods __________ to making ____ a day). ______ __ well as __________ __________ ______ _____ how __________ __________ a __ change ______ ______ P Yes ______ Activity __________ ______ in your __________________ ____ P No __________ pet’s diet? __________ ____________ __________ What are ? ______ How active is __________ your pet’s __________________ ______ __________ ______ your pet? food prefere __________ ____________ ______ ______ ______ Hyperactive __________ nces?_______ ______ __________________ ______P Feeding Manageme ______ ______ ______ ___________ ______ ______ ______ P Very active ______ ______ P Average nt ______ ______ ______ ______ ______ ______ P Not very active _____ ______ ___ Who typically ______ ____ ______ ______ P Hardly ______ ____________ feeds your pet? ______ moves ______ ______ ______ How often is ______ ___________ ______ __________ ______ ______ ______ ______ ____ __________ ______ __________ ____ ______ ______ your pet walked? ______ __________ ____________ ________ ______ ______ What foods ______ __________ ___________ Comme ______ ______ ______ P At least 3 times/day __________ ____ rcial treats; __________ does your ______ ____ ______ __________ __________ P 1-2 times/day ____________ pet dental hygiene ______ ______ __ __________ ___________ ______ P Seldom P Once a day refuse? ______ ______ __________ When is your ____ ______ __________ P______ products Never ____ ______ ______ pet fed? __________ ______ ______ ______ __________ ______ __ ______ Do you have ______ ______ ______ __________ ______ ______ __________ _____ ________________ ______ ______ ______ access to a yard? __________ ______ ____ ______ ______ ______ P ______ __________ Is it difﬁcult ______ _______ ______ ______ ______ ______Yes P No ______ __________ __________ to exercise ____ ______ __________ ____________ ___ ______ ______ ____pet? your __________ ______ ______ ______ __________ Are there P Yes ______ Can exercise ________ _______ ______ ______ ______ __________ ______ __________ be increased? foods to P No ____ ___ ______ __________ ____________ ______ ____ __________ ______ ______ __________ If so, which P Yes which your pet Has your____________ ________ _______ ______ ______ __________ is allergic ____ ___ ______ __________ ____________ pet participated foods? P No ____ in training? ? P ______ ______ Has your______ Yes P ______ ________ ______ P Yes pet participated ______ ______ No ______ ____ in competition ____________P No ______ ______ ? ______ ______ __________ ______ P Yes P______ ______ ______ ______ ______ ___ ______ ____ ______ No ______ ______ ______ _________ ______ ______ ______ ____ ______ __ ______ ______ ______ _________ ______ ______ ____ ______ __ ______ _________ ______ ____ __

WEB EXCLUSIVE

VIDEOS

NEWS BITES

❯❯ Canine DNA Patch for Muscular Dystrophy Leads to Human Testing Using a novel genetic technology that covers up genetic errors, researchers have developed a successful treatment for dogs with the canine version of muscular dystrophy.

❯❯ Genetic Link Identiﬁed Between Feline and Human Eye Diseases A University of Missouri researcher’s discovery could help in developing therapies for humans and cats with forms of retinitis pigmentosa.

❯❯ Biologic Trojan Horse Leads Dogs on Therapeutic Odyssey The story of a “miracle dog” provides hope to dog owners and points to a powerful new cancer treatment for humans—one that inﬁltrates cancer cells like a biologic Trojan horse.

❯❯ Laparoscopic Organ Biopsy Videos The April 2009 Surgical Views column, “Techniques for Laparoscopic and Laparoscopic-Assisted Biopsy of Abdominal Organs,” by Dr. Philipp Mayhew, describes laparoscopic techniques that can be used to harvest biopsy samples from the liver, kidneys, pancreas, and gastrointestinal tract. Six videos, contributed by Dr. Mayhew and Stephen J. Mehler, DVM, DACVS, demonstrate the use of some of the techniques and instruments discussed in this article.

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.

Compendium

153

Antioxidants in Cancer Treatment: Helpful or Harmful? ❯❯ Lisa M. Freeman, DVM, PhD, DACVN,a Tufts University

Abstract: Nutrition is an important component of the care of dogs and cats with cancer, and dietary supplement use is common in this patient population. Antioxidants are thought to be among the most commonly used supplements. While antioxidants have potential benefi ts for cancer patients, they also may have detrimental effects. Therefore, information regarding the overall diet, including dietary supplements, should be collected for every cancer patient and carefully assessed, with specific attention to antioxidants, to identify areas in which the patient’s medical care can be optimized. eterinarians are commonly faced with to avoid excesses of overall calories and indiquestions from pet owners about nutri- vidual nutrients. Obesity resulting from excestion, but when an animal has cancer, sive caloric intake is a common problem in such questions are even more likely. Most own- animals with cancer.1,2 Body weight, body ers of dogs and cats with cancer want to know condition score, and muscle condition (i.e., everything from whether diet contributed to whether muscle loss is occurring) should be the development of the cancer to whether assessed at each visit. Obtaining a thorough they should change their pet’s diet to whether diet history allows the veterinarian to deterdietary supplements should be administered mine whether the animal is eating an approas part of their pet’s treatment. Advertisements priate diet, whether deficiencies or excesses for dietary supplements abound in magazines are likely to occur, and whether components for pet owners and veterinarians alike, and it of the diet are working with or against the can be tempting for owners of pets with can- selected therapeutic plan for the patient. This cer to believe the claims of disease treatments information can then be used to make necesor cures that are supposed to come from a sary modifications to ensure optimal care. few pills. If owners do not ask their veterinarians questions about these claims, they often The Importance of Diet History use the Internet to try to get the answers for Dietary supplementation is extremely comthemselves. Therefore, it is important to be mon in today’s society. More than half of all aware of both the potential benefits and risks Americans take dietary supplements on a regular basis.4–6 Fewer pets in the general populaof dietary supplements. tion receive dietary supplements; in one study Nutrition in Pets With Cancer of pet owners, approximately only 10% of dogs Nutrition should be an integral part of the and cats were receiving supplements, with management of every cancer patient. Cancer multivitamins, chondroprotectives, and fatty patients may be predisposed to weight loss, acid supplements being the most common.7 malnutrition, and specific nutrient deficien- However, in populations with disease condicies during treatment. Therefore, it is impor- tions, dietary supplement use is higher. Dietary tant to maintain optimal weight and prevent supplements are used in 31% of dogs and 13% nutritional deficiencies in these patients to of cats with cardiac disease, respectively,8,9 and improve their outcome.1–3 It is also important in >50% of dogs and cats with cancer.10 People

QuickNotes It is important to maintain optimal weight and prevent nutritional deﬁciencies in cancer patients to improve their outcome.

Dr. Freeman discloses that she has received research funding from Nestlé Purina PetCare, Boehringer Ingelheim, and the Waltham Centre for Pet Nutrition and that she has served on a Nestlé Purina Scientiﬁc Advisory Council.

154

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

What do dogs who take e VETORYL (trilostane) have in common? ®

Results like these.

Prior to VETO RYL treatment

Effective treatment for Cushing’s syndrome is now FDA approved. You now have easy access to the most powerful weapon in the fight against canine Cushing’s syndrome. VETORYL Capsules are the only licensed treatment available for both pituitary-dependent and adrenal-dependent hyperadrenocorticism.

treatment Following 3 months of with VETORYL

VETORYL Capsules contain the active ingredient trilostane, which blocks the excessive production of cortisol. Daily administration of VETORYL can greatly reduce the clinical signs associated with Cushing’s syndrome, enhancing the quality of life for both dog and owner. For more information, visit www.VETORYL.com. Contact your local veterinary distributor to order VETORYL Capsules today!

Following 9 months of treatment with VETO RYL

(trilostane)

Photographs courtesy of Carlos Melian, DVM, PhD

VETORYL is a trademark of Dechra Ltd. ©2009, Dechra Ltd. NADA 141-291, Approved by FDA As with all drugs, side effects may occur. In field studies, the most common side effects reported were poor/reduced appetite, vomiting, lethargy, diarrhea, and weakness. Occasionally, more serious side effects, including severe depression, hemorrhagic diarrhea, collapse, hypoadrenocortical crisis, or adrenal necrosis/rupture may occur, and may result in death. VETORYL Capsules are not for use in dogs with primary hepatic or renal disease, or in pregnant dogs. Refer to the prescribing information for complete details or visit www.VETORYL.com. VTYL0209-01-47122-CPD

See Page 156 for Product Information Summary

VETORYL Capsules (trilostane) ®

30 mg and 60 mg strengths Adrenocortical suppressant for oral use in dogs only

with chronic diseases use supplements even more commonly than the general population, and only a small proportion of these patients tell their health care providers about their supplement use.11 With the increase in supplement use in populations with diseases comes an increased risk for interaction between supplements or between supplements and medications. Because animals with cancer are one of the most likely populations to be receiving dietary supplements, an important part of a thorough diet history is to specifically ask owners if they are giving supplements to their pets. A thorough diet history is one of the keys to providing optimal care for animals with cancer. Questions should include the specific food (brand and specific type), amounts and frequency of feeding, types and amounts of treats and table foods, whether the animal is eating an unconventional diet (e.g., homemade, raw meat), and whether dietary supplements are being used. Dietary supplements can be a particular issue because owners often do not consider them to be either drugs or part of the diet. Therefore, if owners are not specifically questioned about the use of dietary supplements, they usually do not mention them. Veterinarians should ask about the types, brands, and doses of supplements being administered. This information can help to determine whether supplements are being used and dosed appropriately and whether they might interact with any drugs or nutrients being used as therapy.

BRIEF SUMMARY (For Full Prescribing Information, see package insert.) CAUTION: Federal (USA) law restricts this drug to use by or on the order of a licensed veterinarian. DESCRIPTION: VETORYL is an orally active synthetic steroid analogue that blocks production of hormones produced in the adrenal cortex of dogs. INDICATIONS: VETORYL Capsules are indicated or the treatment of pituitary-dependent hyperadrenocorticism in dogs. VETORYL Capsules are indicated for the treatment of hyperadrenocorticism due to adrenocortical tumor in dogs. CONTRAINDICATIONS: The use of VETORYL Capsules is contraindicated in dogs that have demonstrated hypersensitivity to trilostane. Do not use VETORYL Capsules in animals with primary hepatic disease or renal insufficiency. Do not use in pregnant dogs. Studies conducted with trilostane in laboratory animals have shown teratogenic effects and early pregnancy loss. WARNINGS: In case of overdosage, symptomatic treatment of hypoadrenocorticism with corticosteroids, mineralocorticoids and intravenous fluids may be required. Angiotensin-converting enzyme (ACE) inhibitors should be used with caution with VETORYL Capsules, as both drugs have aldosterone-lowering effects which may be additive, impairing the patient’s ability to maintain normal electrolytes, blood volume and renal perfusion. Potassium-sparing diuretics (e.g., spironolactone) should not be used with VETORYL Capsules as both drugs have the potential to inhibit aldosterone, increasing the likelihood of hyperkalemia. HUMAN WARNINGS: Keep out of reach of children. Not for human use. Wash hands after use. Do not empty capsule contents and do not attempt to divide the capsules. Do not handle the capsules if pregnant or if trying to conceive. Trilostane is associated with teratogenic effects and early pregnancy loss in laboratory animals. In the event of accidental ingestion/overdose, seek medical advice immediately and take the labeled container with you. PRECAUTIONS: Hypoadrenocorticism can develop at any dose of VETORYL Capsules. A small percentage of dogs may develop corticosteroid withdrawal syndrome within 10 days of starting treatment. Mitotane (o,p’-DDD) treatment will reduce adrenal function. Experience in foreign markets suggests that when mitotane therapy is stopped, an interval of at least one month should elapse before the introduction of VETORYL Capsules. The use of VETORYL Capsules will not affect the adrenal tumor itself. Adrenalectomy should be considered as an option for cases that are good surgical candidates.

QuickNotes

There is a great deal of controversy among human oncologists as Antioxidants to whether antioxiAntioxidants are thought to be among the most comdants are beneﬁcial, monly used dietary supplements in animals with cancer. They are typically administered with the goal of innocuous, or aiding in the treatment of cancer, enhancing immune detrimental. function, or reducing treatment toxicity. Endogenous antioxidants include enzymes (e.g., glutathione peroxidase, superoxide dismutase), free radical scavengers (e.g., vitamins A, C, and E), and metal chelators (e.g., transferrin). Normally, these antioxidants compensate for the production of oxidants known as reactive oxygen species (e.g., hydrogen peroxide, superoxide anions, hydroxyl radicals), which are normal by-products of

ADVERSE REACTIONS: The most common adverse reactions reported are poor/reduced appetite, vomiting, lethargy/dullness, diarrhea, and weakness. Occasionally, more serious reactions including severe depression, hemorrhagic diarrhea, collapse, hypoadrenocortical crisis, or adrenal necrosis/rupture may occur, and may result in death. ORY FORM DIET HIST Stamp clinic

information below:

_______ ________________ ________________ ________ Date: ________ ________________ ________________ Case Number: n _______ Owner Informatio ________________ ________________ ________ Name: ________ ________________ ________ ________________ Email address: ________________ ________________ __________ Phone (home): ________________ __________ ________________ Phone (cell): ________________ call:_____________ Best time to

DIET HISTORY FORM Behavior

❏ Yes

❏ No

How does your pet act toward towa food? ❏ Greedy ❏ Indifferen Indifferent ❏ Shows avoidance Has your pet’s attitude toward towa food changed? If so, describe: _______________________ ________________________ ________________________ ____ _______________________ ________________________ ________________________ ____ _______________________ ________________________ ________________________ ____ _______________________ ________________________ ________________________ ____ If you have other pets, is this pet dominant or submissive to them? ❏ Dominant ❏ Submis Submissive Has your pet recently lost or ggained weight? If so, please describe: _______________________ ________________________________________________ ____ ________________________________________________ ____ ________________________________________________ ____ ________________________________________________ ____ Have there been any recent ch changes in activity level? __________ ________________________________________________ ____ ________________________________________________ ____ ________________________________________________ ____ Have you observed any of the ffollowing: Nausea/salivation ❏ Yes ❏ No Diffificulty chewing ❏ Yes ❏ No Diffificulty swallowing ❏ Yes ❏ No Vomiting ❏ Yes ❏ No Diarrhea ❏ Yes ❏ No Constipation ❏ Yes ❏ No Have there been any changes in urination? ❏ Yes ❏ No

the day? for your pet during ed food sources Is food left out other, unmonitor have access to cats)? Does your pet food left for outdoor by neighbor, (e.g., treats fed _______ ❏ Yes ❏ No ________________ ____ describe:_________ If yes, please ________________ ________________ ____ ________________ ________________ ________________ ____ ________________ ________________ ________________ ____ ________ ________ ________________ ________________ to each other’s ________________ _ have access one pet, do they ________________ than Reason for Visit more ________ If you have ____ please describe: ________________ ❏ No If yes, ________________ ___________ ____________ food? ❏ Yes ________________ ________________ ____________ ________ ____ ________ ________________ ________________ ________________ ________________ ________________ ________________ ____________ ________________ ________________ ________ ____ ___ hics ________ ________________ ________________ Household Demograp ? ________ ________________ ____ are in your household are they? ________________ ________________ How many adults , and how old ________________ ____ ____ are in your household ________________ ________________ ________________ How many children ________________ ____ ________________ ____________ ________________ ________________ ________________ ________________ ________ ________ ____ ________ ________________ ________________ ________________ ________________ food? ________ ____ ________________ store your pet’s ____________ How do you ________________ ________________ ________________ ________ ________ ____ ________ ❏ Both ❏ Outdoors ________________ ________________ ________________ ❏ Indoors ________________ pet housed? ____________ please list species ________________ Where is your ❏ No If so, ________________ Yes ❏ ________ other pets? ________________ Do you have or outdoors. ____ they live indoors Diet and specify if ________________ ____ ________________ Activity For each of the following categories, catego ________________ ________________ list the brand names (if appliyour pet? ____ ________________ cable) and amounts of all foods your How active is ❏ Average pet eats daily, as well as how ________________ ________________ Very active ❏ ________ e often each food is fed (e.g., twice ____ ________ twic a day). ❏ Hyperactiv ________________ ________________ ❏ Hardly moves Commercial foods ____ ________________ ❏ Not very active ________________ ________________ your pet walked? ________________________________________________ ________________ ❏ Once a day __ How often is ____ ________________ ❏ 1-2 times/day times/day ________________________________________________ ❏ At least 3 __ ____ ____ ent Never No ❏ ________ ❏ ________________________________________________ ❏ Yes Feeding Managem ❏ Seldom __ ________________ ____ ____ feeds your pet? access to a yard? ________________ ❏ Yes ❏ No ________________________________________________ Who typically Do you have __ pet? ____ ____ ________________ your No ________ ________ exercise ________ ________________________________________________ ________ ❏ Yes ❏ Is it difﬁcult to ___ ________________ ____ __________ be increased? ________________ ❏ Yes ❏ No Commercial treats; dental hygiene products ________________ Can exercise ____ training? pet fed? ________ participated in ________________ When is your ❏ Yes ❏ No ________________________________________________ Has your pet ___ ____ ________________ competition? ____ participated in ________________ ________________ ________________________ Has your pet Systems ___ ________________________ ____ ________________ Learning ____ ________ ________ ©2009 Veterinary ________ ________ ________________________________________________ ___ ________________ ____ ________________ ________________________________________________ ___ ____ ________________________________________________ ___ ____

(trilostane)

n Age: ________ Pet Informatio __________ ________________ ___________ Name: ________ Breed: ________ _____________ ❏ Yes ❏ No Species: ________ Neutered/spayed: ❏ Female _____________ Gender: ❏ Male Usual weight: _____________ Current weight: _____ score (1–9): ❏ Severe Body condition None ❏ Mild wasting ❏ muscle of Evidence

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Table foods or scraps; home-prepared

foods

________________________________________________ ____ ________________________________________________ ____ ________________________________________________ ____ ________________________________________________ ____ ________________________________________________ ____ Dietary supplements; food used to give pills ________________________________________________ ____ ________________________________________________ ____ ________________________________________________ ____ ________________________________________________ ____ ________________________________________________ ____ List anything else given by mouth (e.g., medications): ________________________________________________ ____ ________________________________________________ ____ ________________________________________________ ____ ________________________________________________ ____ ________________________________________________ ____ ________________________________________________ ____ Is your pet’s current diet a change from its typical diet? ❏ Yes

❏ No

If so, please describe the change and why the diet was changed. ________________________________________________ ____ ________________________________________________ ____ ________________________________________________ ____ ________________________________________________ ____ ________________________________________________ ____ ________________________________________________ ____ Are you open to making a change in your pet’s diet? ❏ Yes ❏ No What are your pet’s food preferences?______________ ________ ________________________________________________ ____ ________________________________________________ ____ ________________________________________________ ____ What foods does your pet refuse? ________________________ _ ________________________________________________ ____ ________________________________________________ ____ ________________________________________________ ____ Are there foods to which your pet is allergic? ❏ Yes ❏ No If so, which foods? ________________________ ____________ ________________________________________________ ____ ________________________________________________ ____ ________________________________________________ ____ ©2009 Veterinary Learning Systems

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CONTRIBUTED BY THE AMERICAN COLLEGE OF VETERINARY NUTRITION

aerobic metabolism. However, when oxidant production is excessive or antioxidant production is insufficient, an imbalance known as oxidative stress occurs. Excessive oxidants damage DNA, lipids, and proteins and increase the production of inflammatory mediators, among other deleterious effects. It has been hypothesized that oxidative stress increases the risk for certain types of cancer, and it is theorized to play an important role in the aging process. Therefore, antioxidants (both endogenous and supplemental) have been extensively studied in terms of their efficacy in reducing the development of cancer, with variable success. Another area of great interest and controversy is the use of antioxidants during the treatment of cancer, whether alone or in conjunction with chemotherapy or radiation therapy. Antioxidants have a number of potential benefits in cancer patients. Oxidative stress has been associated with increased morbidity and mortality for a number of human cancers, and recent studies have demonstrated oxidative stress in dogs with mammary tumors and lymphoma.12–14 Reactive oxygen species can contribute to malignant transformation and neoplastic cell proliferation and so could contribute to disease progression. Therefore, boosting antioxidant reserves and reducing oxidative stress might reduce tumor growth or metastasis. Another potential benefit of antioxidants is protection against radiation- and chemotherapyinduced adverse effects (e.g., gastrointestinal, renal, and cardiac toxicities); some, but not all, studies in rodent models and people have shown modest benefits. These potential benefits are the rationale behind the high use of various antioxidants during cancer treatment. However, there also are potential detrimental effects of antioxidants in patients undergoing treatment for cancer. The efficacy of radiation therapy and of many chemotherapeutic agents depends on the development of reactive oxygen species. Therefore, reduced treatment efficacy is possible if antioxidants are used concurrently with these therapies. Because of these competing effects, there is a great deal of controversy among human oncologists as to whether antioxidants are beneficial, innocuous, or detrimental.15–17 Antioxidants do not all behave similarly, and some have significantly different effects depending on their dose and form and what other medications and supple-

About ACVN

BOX 1 HEALTHY BITES

Recommended Web Sites www.acvn.org The American College of Veterinary Nutrition Offers a “Nutrition Resources” page that includes contact information for ACVN diplomates who do nutrition consultations or formulate homemade diets. www.consumerlab.com Consumerlab.com This group performs independent testing of dietary supplements for purity, potency, and bioavailability. vm.cfsan.fda.gov/~dms/supplmnt.html The US Food and Drug Administration Center for Food Safety and Applied Nutrition Resource for regulatory and safety issues, adverse event reporting, meetings, and industry information. www.mayoclinic.com/health/ druginformation/DrugHerbIndex The Mayo Clinic Lists information and grades recommendations for the use of some drugs and supplements. nccam.nih.gov National Institutes of Health National Center for Complementary and Alternative Medicine Provides information on research into complementary and alternative healing practices. dietary-supplements.info.nih.gov National Institutes of Health Ofﬁce of Dietary Supplements Includes fact sheets, safety notices, and the International Bibliographic Information on Dietary Supplements database. www.quackwatch.org Quackwatch This site calls itself a “guide to health fraud, quackery, and intelligent decisions.” www.nal.usda.gov/fnic/etext/000015.html The US Food and Drug Administration Food and Nutrition Information Center Includes general supplement and nutrition information and links to a variety of dietary supplement Web sites.

Founded in 1988, the primary objective of the American College of Veterinary Nutrition (ACVN) is to advance the specialty area of veterinary nutrition and increase the competence of those who practice in this ﬁeld by establishing requirements for certiﬁcation in veterinary nutrition, encouraging continuing professional education, promoting research, and enhancing the dissemination of new knowledge of veterinary nutrition through didactic teaching and postgraduate programs. For more information, contact: American College of Veterinary Nutrition, c/o Dawn Cauthen, Administrative Assistant, School of Veterinary Medicine: Dept. of Molecular Biosciences One Shields Avenue Davis, California 95616-8741 Telephone: 530-752-1059 Fax: 530-752-4698 Email: dawncauthen@yahoo.com Web: acvn.org

QuickNotes Once veterinarians determine what foods and supplements owners are giving their pets, they may need to gather additional information about their safety, efﬁcacy, and potential for interaction.

www.usp.org/USPVerified US Pharmacopeia Dietary Supplement Verification Program (voluntary) This group performs independent testing of “dietary supplement finished products” for purity, potency, and quality and awards its Verified Dietary Supplement Mark to products that meet its criteria.

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ments are being concurrently administered. Therefore, evaluating whether one has benefits (or adverse effects) can be a complicated endeavor. In addition to the specific pros and cons of antioxidants are the general issues that are of concern with all human and veterinary dietary supplements: safety, efficacy, dose, bioavailability, dissolvability, and quality control. Until additional data are available, I recommend against the use of antioxidants during radiation therapy or chemotherapy in dogs and cats with cancer.

Conclusion Once veterinarians determine what foods and supplements owners are giving their pets, they may need to gather additional information about their safety, efﬁcacy, and potential for interaction with each other and other therapies. Some of the Web sites listed in BOX 1 can be useful for this purpose. Because there is little governmental regulation of dietary supplements, pet owners should consider selecting dietary supplements that bear the logo of the Dietary Supplement Veriﬁcation Program, which tests human dietary supplements for ingredients, concentrations, dissolvability, and contaminants. Another good resource is Consumerlab.com, which performs independent testing of health and nutrition products (primarily human supplements, but also some pet products). As of 2008 (2009 or 2010 for smaller companies), the US Food and Drug Administration is instituting regulations that require supplements to be made using Good Manufacturing Practices and to meet quality standards.18

References 1. Michel KE, Sorenmo K, Shofer FS. Evaluation of body condition and weight loss in dogs presented to a veterinary oncology service. J Vet Intern Med 2004;18:692-695. 2. Weeth LP, Fascetti AJ, Kass PH, et al. Prevalence of obese dogs in a population of dogs with cancer. Am J Vet Res 2007;68:389-398. 3. Baez JL, Michel KE, Sorenmo K, Shofer FS. A prospective investigation of the prevalence and prognostic significance of weight loss and changes in body condition in feline cancer patients. J Feline Med Surg 2007;9:411-417. 4. Balluz LS, Kieszak MA, Philen RM, et al. Vitamin and mineral supplement use in the United States: results from the third national health and nutrition examination survey. Arch Fam Med 2000;9:258-262. 5. Balluz LS, Okoro CA, Bowman BA, et al. Vitamin or supplement use among adults, behavioral risk factor surveillance system, 13 states, 2001. Public Health Rep 2005;120:117-123. 6. Archer SL, Stamler J, Moag-Stahlberg A, et al. Association of dietary supplement use with speciﬁc micronutrient intakes among middle-aged American men and women: the INTERMAP study. J Am Diet Assoc 2005;105:1106-1114. 7. Freeman LM, Abood SK, Fascetti AJ, et al. Disease prevalence among dogs and cats in the United States and Australia and proportions of dogs and cats that receive therapeutic diet or dietary supplements. JAVMA 2006;229:531-534. 8. Freeman LM, Rush JE, Cahalane AK, et al. Dietary patterns in dogs with cardiac disease. JAVMA 2003; 223:1301-1305.

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9. Torin DS, Freeman LM, Rush JE. Dietary patterns of cats with cardiac disease. JAVMA 2007;230:862-867. 10. Lana SE, Kogan LR, Crump KA, et al. The use of complementary and alternative therapies in dogs and cats with cancer. JAAHA 2006;42:361-365. 11. Ball SD, Kertesz D, Moyer-Mileur LJ. Dietary supplement use is prevalent among children with a chronic disease. J Am Diet Assoc 2005;105:78-84. 12. Szczubial M, Kankofer M, Lopuszynski W, et al. Oxidative stress parameters in bitches with mammary gland tumours. J Vet Med A Physiol Pathol Clin Med 2004;51:336-340. 13. Vajdovich PT, Kriska T, Mezes M, et al. Redox status of dogs with non-Hodgkin lymphomas. An ESR study. Cancer Lett 2005;224:339-346. 14. Winter JL, Barber L, Griessmayr PC, et al. Antioxidant status and biomarkers of oxidative stress in canine lymphoma. J Vet Intern Med 2009;23:311-316. 15. D’Andrea GM. Use of antioxidants during chemotherapy and radiotherapy should be avoided. CA Cancer J Clin 2005;55:319-321. 16. Block KI, Koch AC, Mead MN, et al. Impact of antioxidant supplementation on chemotherapeutic efﬁcacy: A systematic review of the evidence from randomized controlled trials. Cancer Treat Rev 2007;33:407-418. 17. Moss RW. Do antioxidants interfere with radiation therapy for cancer? Integr Cancer Ther 2007;6:281-292. 18. United States Food and Drug Administration. Fact sheet: dietary supplement current good manufacturing practices (CGMPs) and interim ﬁnal rule (IFR) facts. Accessed March 2009 at www.cfsan.fda.gov/~dms/dscgmps6.html.

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My patients rely on me every day. And I rely on Baytril®. Because when it comes to infections, it’s on my side – an eﬀective partner I can count on. Federal (U.S.A.) law restricts this drug to use by or on the order of a licensed veterinarian. In animal safety studies, isolated incidences of vomition and inappetence were reported. © 2009 Bayer HealthCare LLC, Animal Health Division, Shawnee Mission, Kansas 66201. Bayer, the Bayer Cross, Baytril and Right the ﬁrst time are registered trademarks of Bayer.

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B090123n

3 CE CREDITS

CE Article 1

Intracranial Arachnoid Cysts in Dogs ❯❯ Curtis W. Dewey, DVM, MS, DACVIM (Neurology), DACVSa ❯❯ Peter V. Scrivani, DVM, DACVR ❯❯ Ursula Krotscheck, DVM, DACVS ❯❯ Soﬁa Cerda-Gonzalez, DVM, DACVIM (Neurology) Cornell University

❯❯ Kerry Smith Bailey, DVM, DACVIM (Neurology) Oradell Animal Hospital Paramus, New Jersey

❯❯ Dominic J. Marino, DVM, DACVS Long Island Veterinary Specialists Plainview, New York

At a Glance

Abstract: Intracranial arachnoid cyst (IAC) is an infrequently reported developmental disorder seen primarily in small-breed dogs. It usually occurs in the caudal fossa, in the region of the quadrigeminal cistern. Although still considered uncommon, IAC is being recognized more frequently in veterinary medicine, coinciding with the increased availability of magnetic resonance imaging. In this article, clinical information from previously reported cases of canine IAC is combined with additional case information from our hospitals. Similar to IAC in people, it is thought that canine IAC is often an incidental finding. When IAC is responsible for neurologic disease in dogs, generalized seizures and cerebellovestibular dysfunction are the most common clinical presentations. Medical therapy of IAC focuses on management of increased intracranial pressure and seizures, if the latter are part of the clinical complaints. Surgical therapy of IAC involves either cyst fenestration or shunting the excess fluid to the peritoneal cavity.

ntracranial arachnoid cyst (IAC), also called intracranial intraarachnoid cyst and quadrigeminal cyst, is a developmental brain disorder in which cerebrospinal ﬂuid (CSF) is thought to accumulate within a split of the arachnoid membrane.1 Although IACs have been reported to occur in several locations in humans, all reported canine cases have been in the

caudal fossa.2–11 Because IAC is typically associated with the quadrigeminal cistern in dogs, these accumulations of ﬂuid are often called quadrigeminal cysts in this species and have a characteristic appearance on magnetic resonance imaging (MRI) scans4–6,10,11 (FIGURE 1). IACs account for 1% of all intracranial masses in people and are often considered incidental ﬁndings.12–14

FIGURE 1

Breed Distribution Page 162

Pathogenesis Page 162

Clinical Features Page 162

Diagnosis Page 164

Clinical Signs Page 165

Medical Therapy Options Page 165

Treatment and Prognosis Page 165

Dr. Dewey discloses that he has received ﬁnancial support from Boehringer-Ingelheim.

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Midsagittal T2-weighted image of a dog’s brain demonstrating the characteristic appearance of an IAC in this species. The asterisk is in the center of the cyst. (Reprinted with permission from Dewey CW. Encephalopathies: disorders of the brain. In: Dewey CW, ed. A Practical Guide to Canine and Feline Neurology. 2nd ed. Ames, Iowa: Wiley-Blackwell; 2008:115-120.)

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Intracranial Arachnoid Cysts in Dogs CE

Dr. Dewey is an associate professor of neurology and neurosurgery and chief of the section of neurology at Cornell University.

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FREE CE Intracranial Arachnoid Cysts in Dogs

QuickNotes When there is evidence of a large IAC and another disease (e.g., granulomatous meningoencephalomyelitis, hydrocephalus) in the same patient, the optimal response to treatment may require treating both conditions.

162

There are 10 clinical reports of IAC in dogs in the veterinary literature. 2–11 This review combines these reported cases with three additional cases from our hospitals to present information regarding 56 dogs with IAC. Most reported cases of IAC in dogs are in small breeds, with a predominance of brachycephalic animals. 2–11 Shih tzus may be overrepresented.11,15 Male sex also appears to be a predisposing factor. Clinical signs attributable to IAC in dogs are most often related to cerebral or cerebellar compression by the cyst; generalized seizures and central vestibular dysfunction are most commonly noted.15 Similar to human IACs, a large proportion of reported IACs in dogs were suspected to be incidental.4–6,11 Medical and surgical options are available to treat IAC in dogs.

Pathogenesis IACs are believed to represent a developmental abnormality caused by an aberrant split in the arachnoid membrane during embryogenesis.1,12 The developing neural tube is surrounded by a loose layer of mesenchymal BOX 1

Breed Distribution of Reported Intracranial Arachnoid Cysts in Dogs Shih tzu . . . . . . . . . . . . . . . . . . . . . . . . . 15 dogs Maltese . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .4 Pug . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .4 Lhasa apso . . . . . . . . . . . . . . . . . . . . . . . . . . . . .4 Cavalier King Charles spaniel . . . . . . . . . . . .4 Yorkshire terrier . . . . . . . . . . . . . . . . . . . . . . . .4 Chihuahua. . . . . . . . . . . . . . . . . . . . . . . . . . . . . .3 Staffordshire bull terrier . . . . . . . . . . . . . . . . .3 Bulldog. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .3 Pekingese . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .2 West Highland white terrier . . . . . . . . . . . . . .2 Bichon frise . . . . . . . . . . . . . . . . . . . . . . . . . . . .1 Pomeranian . . . . . . . . . . . . . . . . . . . . . . . . . . . .1 Cairn terrier. . . . . . . . . . . . . . . . . . . . . . . . . . . . .1 Jack Russell (Parson Russell) terrier . . . . . .1 Terrier mix. . . . . . . . . . . . . . . . . . . . . . . . . . . . . .1 Beagle . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .1 Miniature schnauzer. . . . . . . . . . . . . . . . . . . . .1 German shorthaired pointer . . . . . . . . . . . . .1

tissue called the perimedullary mesh; this tissue eventually becomes the pia and arachnoid layers of the meninges. In normal development, pulsatile CSF ﬂow from the choroid plexuses is thought to divide the perimedullary mesh into the pia and arachnoid layers, effectively creating the subarachnoid space. It is postulated that some aberration of CSF ﬂow from the choroid plexuses during this stage of development forces a separation within the forming arachnoid layer, eventually leading to the creation of an IAC.1,12 The intraarachnoid location of IACs has been demonstrated via light and electron microscopy in people.1 Depending on whether these cysts communicate with the subarachnoid space or the ventricular system, they are sometimes referred to as communicating or noncommunicating.1 The mechanisms by which an IAC continues to expand with fluid are unknown, but several theories have been proposed.1,12 There is evidence that arachnoid cells lining the IAC may have secretory capacity.1,12,16 Fluid may also move into the cyst via an osmotic pressure gradient. However, considering that the fluid within the IAC is nearly identical to CSF, this theory is unlikely.1,12 In addition, there have been documented cases in people in which small slits exist between the IAC and the subarachnoid space; these slits act as one-way valves, diverting CSF into the cyst during systole and preventing its return to the subarachnoid space during diastole.1,12,17

Clinical Features Most reported dogs with IAC have been small breeds, and many had brachycephalic conformation. The following information was obtained by combining the IAC cases reported in the literature with three additional cases from our hospitals. The breed distribution of these 56 dogs is listed in BOX 1. Approximately 66% of the dogs (37 of 56) were male.2–11 There is a wide age range at clinical presentation for dogs with IAC (2 months to 12 years), with an approximate average age of 4 years. The most common clinical signs (BOX 2) seen with IAC are reﬂective of forebrain or central vestibular (cerebellovestibular) dysfunction. Other reported clinical signs include neck pain, paraparesis, and tetraparesis.2–11

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FREE CE Intracranial Arachnoid Cysts in Dogs

Diagnosis Diagnosis of IAC in dogs is typically made via computed tomography (FIGURE 2) or, preferably, MRI.2–5,7–10 IACs may also be visualized using ultrasound (via the foramen magnum, temporal window, or persistent bregmatic fontanelle), especially in younger dogs.6 The characteristic ultrasonographic appearance of IAC is a large, fluid-filled structure, isoechoic with the CSF spaces (e.g., lateral ventricle) and located between the occipital lobe of the cerebrum and rostral lobe of the cerebellum.6 MRI provides the best detail for diagnosis of IAC and is most likely to provide information regarding the presence and nature of concurrent disease states. The typical appearance of IAC on MRI is a well-demarcated, cystic-appearing structure that is hypointense on T1-weighted images, hyperintense on T2-weighted images, and non-contrast enhancing with intravenous gadolinium administration and that suppresses on FLAIR (fluid attenuation inversion recovery) images2–5,10,11 (FIGURE 3). Because IAC may be an incidental finding, it is important to rule out concurrent inflammatory disease with a CSF examination. In the absence of an additional brain disorder, the CSF is typically normal in dogs with IAC. In our opinion, it is often difficult or impossible to discern whether a large IAC in the

presence of another brain disorder is purely an incidental fi nding. We have seen a number of patients with relatively small dilations of the quadrigeminal cistern (FIGURE 4), which may represent a variant of normal structure or may be evidence of nascent IACs that may be of no clinical significance. Conversely, very large IACs have been described both as sole disease entities and as suspected incidental findings in patients with other intracranial disease processes. Anecdotally, we have also observed similar cystic structures in the brain that do not appear to be associated with the quadrigeminal cistern (FIGURE 5); considering that IACs occur in multiple locations in the human brain, this finding may simply imply that the term quadrigeminal cyst is too restrictive in describing IAC in dogs.12 Since the presence of a large, fluid-fi lled structure within the cranial vault likely decreases intracranial compliance, some IACs may be contributory rather than incidental findings. In other words, when there is evidence of a large IAC and another disease (e.g., granulomatous meningoencephalomyelitis, hydrocephalus) in the same patient, the optimal response to treatment may require treating both conditions. In addition, the combined presence of hydrocephalus and IAC in a patient does

FIGURE 2 Transaxial Computed Tomography Images

Preoperative (A) and postoperative (B) transaxial computed tomography images from a dog with an IAC treated with cystoperitoneal shunting. In A, the arrowheads are pointing to the ventral aspect of the cyst and the outlined arrowheads are pointing to the dorsal aspect of the cyst. In B, the arrow is pointing to the rostral aspect of the shunt. (Reprinted with permission from Dewey CW, Krotscheck U, Bailey KS, Marino DJ. Craniotomy with cystoperitoneal shunting for treatment of intracranial arachnoid cysts in dogs. Vet Surg 2007;36:416-422.)

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Intracranial Arachnoid Cysts in Dogs CE not necessarily make one of the disorders (IAC) incidental, nor does this combination ensure that surgically treating one disorder will address the other. Hydrocephalus can be secondary to an IAC, developing because of mechanical obstruction of normal CSF flow by the expanding cyst (i.e., obstructive hydrocephalus).10,18,19 It is unlikely that an IAC can be distinguished as communicating or noncommunicating based on standard MRI sequences; such a distinction would likely require either contrast studies or phase-contrast (cine) MRI. In one report of two dogs with IAC, intracystic hemorrhage, which was suspected to have contributed to the development of neurologic dysfunction, was verified at surgery.3 In a recent study, the degree of brain compression by an IAC was calculated from MRI scans of dogs with the disorder, and these measurements were correlated with the presence or absence of clinical dysfunction. It was found that dogs with >14% compression of the occipital lobe always displayed clinical signs and that dogs with compression of both the cerebellum and the occipital lobe were significantly more likely to display clinical signs than dogs with compression of only one region or dogs with no apparent brain compression.11 BOX 2

Clinical Signs Reported in Dogs With Intracranial Arachnoid Cysts* Abnormal mentation Seizures Ataxia Head tilt Strabismus Nystagmus Paraparesis Intention tremors Tetraparesis Visual deﬁcits Neck pain *Because IAC is often considered an incidental ﬁnding, some of these reported clinical signs may be attributable to concurrent intracranial diseases.

Treatment and Prognosis Because IAC in dogs, as in people, is often considered an incidental finding, it is frequently assumed that treatment of the suspected primary disorder (e.g., inﬂammatory brain disease, hydrocephalus) is indicated and the IAC is of little or no clinical consequence. As mentioned above, we question whether this approach is appropriate. In cases in which the IAC is considered the primary disease condition, medical therapy is aimed at reducing brain edema and increased intracranial pressure associated with the IAC, as well as controlling seizure activity if present. Medical treatment for IAC is identical to that described for congenital hydrocephalus (e.g., corticosteroids, diuretics, anticonvulsants if indicated), and dose recommendations for various therapies are summarized in BOX 3.20,21 Dogs with IAC tend to respond initially to medical therapy, but the response may be temporary. BOX 3

Medical Therapy Options for Dogs With Intracranial Arachnoid Cysts Glucocorticoids Prednisone: 0.25–0.50 mg/kg PO q12h

QuickNotes In cases in which the IAC is considered the primary disease condition, medical therapy is aimed at reducing brain edema and increased intracranial pressure associated with the IAC.

Diuretics Furosemide: 0.5–4.0 mg/kg PO q12–24h Acetazolamide: 10 mg/kg PO q6–8h Proton pump inhibitors Omeprazole: 10 mg/kg PO q24h (dogs <20 kg); 20 mg/kg PO q24h (dogs >20 kg) Anticonvulsant drugs Phenobarbital: 3–5 mg/kg PO q12h Potassium bromide: 35 mg/kg PO divided q12h Gabapentin: 10 mg/kg PO q8h Felbamate: 15 mg/kg PO q8h Zonisamide: 5 mg/kg PO q12h (if not on phenobarbital; 10 mg/kg if on phenobarbital) Levetiracetam: 20 mg/kg PO q8h Pregabalin: 3 to 4 mg/kg PO q8–12h* *Dewey CW, Cerda-Gonzalez S, Levine JM, et al. Pregabalin therapy for refractory idiopathic epilepsy in dogs. J Vet Intern Med 2008;22:765.

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FIGURE 3 A

QuickNotes MRI provides the best detail for diagnosis of IAC and is most likely to provide information regarding the presence and nature of concurrent disease states.

Midsagittal (A), dorsal (B), and transaxial (C) T1-weighted MRI scans demonstrating an IAC in a dog. The arrows are pointing to the cyst in all images. FIGURE 4

Midsagittal T1-weighted brain MRI scan of a dog with a small dilation of the quadrigeminal cistern (white arrow). The black arrow indicates the dorsal aspect (tectrum) of the midbrain.

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FIGURE 5

Midsagittal T1-weighted brain MRI scan of a dog, demonstrating a cystic structure (white arrow) associated with the third ventricle, rather than the quadrigeminal cistern (black arrow).

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FREE

Intracranial Arachnoid Cysts in Dogs CE FIGURE 6 Cystoperitoneal Shunt Placement

Placement of the rostral end of a cystoperitoneal shunt in a dog (A) and a postoperative ventrodorsal radiograph (B) demonstrating location of the shunting device (arrowheads). (Reprinted with permission from Dewey CW, Krotscheck U, Bailey KS, Marino DJ. Craniotomy with cystoperitoneal shunting for treatment of intracranial arachnoid cysts in dogs. Vet Surg 2007;36:416-422.)

Surgical management of IAC in people is typically achieved via either cyst fenestration (i.e., making an opening into the cyst wall) or cystoperitoneal shunt (CPS) placement.14,18,19,22–24 Proponents of fenestration cite a high surgical success rate and avoidance of shunt-related complications as reasons for this surgical choice; proponents of CPS report high success rates and avoidance of cyst reexpansion as reasons for the use of this technique.13,14,18,19,22–26 Both fenestration and CPS (FIGURE 6) procedures have been reported in dogs with IAC.2,3,5,7,10 IAC was considered the primary disease in ﬁve reported fenestration cases. Three patients were reimaged after surgery; two of the three dogs had evidence of cyst persistence on MRI. However, only one dog required reoperation.2,3,7 Successful CPS of dogs with IAC has also been

reported.10 The cyst did not reform in any of the shunted cases. The success rate for surgical management of IAC appears to be high in people and dogs, and whether fenestration or CPS is the preferred procedure remains controversial for both species.10 Because of the paucity of reports of surgically managed dogs with IAC as well as the suspected high incidence of this abnormality being an incidental ﬁnding, the actual surgical success rate for IAC treatment in dogs should be regarded as unknown at this time. Hopefully, as information regarding medical and surgical treatment of clinically signiﬁcant IAC in dogs accumulates, the understanding of the natural course of this disorder and the effectiveness of medical and surgical therapies to manage it will improve.

References 1. Rengachary SS, Watanabe I. Ultrastructure and pathogenesis of intracranial arachnoid cysts. J Neuropath Exp Neurol 1981;40:61-83. 2. Vernau KM, Kortz GD, Koblik PD, et al. Magnetic resonance imaging and computed tomography characteristics of intracranial intraarachnoid cysts in 6 dogs. Vet Radiol Ultrasound 1997;38:171-176. 3. Vernau KM, LeCouteur RA, Sturges BK, et al. Intracranial intraarachnoid cyst with intracystic hemorrhage in two dogs. Vet Radiol Ultrasound 2002;43:449-454. 4. Kitagawa M, Kanayama K, Sakai T. Quadrigeminal cisterna arachnoid cyst diagnosed by MRI in ﬁve dogs. Aust Vet J 2003;81:340-343.

5. Duque C, Parent J, Brisson B, et al. Intracranial arachnoid cysts: are they clinically signiﬁcant? J Vet Intern Med 2005;19:772-774. 6. Saito M, Olby NJ, Spaulding K. Identiﬁcation of arachnoid cysts in the quadrigeminal cistern using ultrasonography. Vet Radiol Ultrasound 2001;42:435-439. 7. Platt SR. What is your diagnosis? J Small Anim Pract 2002;43:469-470. 8. Nagae H, Oomura T, Kato Y, et al. A disorder resembling arachnoid cyst in a dog. J Jpn Vet Neurol 1995;2:9-14. 9. Orima H, Fujita M, Hara Y, et al. A case of the dog with arachnoid cyst. Jpn J Vet Imag 1998;10:49-51.

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10. Dewey CW, Krotscheck U, Bailey KS, Marino DJ. Craniotomy with cystoperitoneal shunting for treatment of intracranial arachnoid cysts in dogs. Vet Surg 2007;36:416-422. 11. Matiasek LA, Platt SR, Shaw S, Dennis R. Clinical and magnetic resonance imaging characteristics of quadrigeminal cysts in dogs. J Vet Intern Med 2007;21:1021-1026. 12. Cincu R, Agrawal A, Eiras J. Intracranial arachnoid cysts: current concepts and treatment alternatives. Clin Neurol Neurosurg 2007;109:837-843. 13. Erdincler P, Kaynar MY, Bozkus H, et al. Posterior fossa arachnoid cysts. Br J Neurosurg 1999;13:10-17. 14. Kandenwein JA, Richter HP, Borm W. Surgical therapy of symptomatic arachnoid cysts—an outcome analysis. Acta Neurochir (Wien) 2004;146:1317-1322. 15. Dewey CW. Encephalopathies: disorders of the brain. In: Dewey CW, ed. A Practical Guide to Canine and Feline Neurology. 2nd ed. Ames, Iowa: Wiley-Blackwell; 2008:115-120. 16. Go KG, Houthoff HJ, Blaauw EH, et al. Arachnoid cyst of the sylvian ﬁssure: evidence of ﬂuid secretion. J Neurosurg 1984;60:803-813. 17. Santamarta D, Aguas J, Ferrer E. The natural history of arachnoid cysts: endoscopic and cine-mode MRI evidence of a slit-valve mechanism. Minim Invasive Neurosurg 1995;38:133-137.

18. Raffel C, McComb JG. To shunt or fenestrate: which is the best surgical treatment for arachnoid cysts in pediatric patients? Neurosurgery 1988;23:338-342. 19. Locatelli D, Bonfanti N, Sfogliarini R, et al. Arachnoid cysts: diagnosis and treatments. Childs Nerv Syst 1987;3:121-124. 20. Coates JR, Axlund TW, Dewey CW, Smith J. Hydrocephalus in dogs and cats. Compend Contin Educ Pract Vet 2006;28:136-146. 21. Dewey CW. Anticonvulsant therapy in dogs and cats. Vet Clin North Am Small Anim Pract 2006;36:1107-1127. 22. Ciricillo SF, Cogen PH, Harsh GT, et al. Intracranial arachnoid cysts in children: a comparison of the effects of fenestration and shunting. J Neurosurg 1991;74:230-235. 23. Kaplan BK, Mickle JP, Parkhurst R. Cystoperitoneal shunting for congenital arachnoid cysts. Childs Brain 1984;11:304-311. 24. Stein SC. Intracranial developmental cysts in children: treatment by cystoperitoneal shunting. Neurosurgery 1981;8:647-650. 25. Kim SK, Cho BK, Chung YN, et al. Shunt dependency in shunted arachnoid cyst: a reason to avoid shunting. Pediatr Neurosurg 2002;37:178-185. 26. Gangemi M, Maiuri F, Colella G, et al. Endoscopic treatment of quadrigeminal cistern arachnoid cysts. Minim Invasive Neurosurg 2005;48:289-292.

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. In dogs, all reported cases of IAC have been in the _________ fossa. a. rostral b. middle c. caudal d. none of the above 2. Formation of IACs in dogs is believed to be due to a. a split in the arachnoid meningeal layer during embryogenesis. b. failure of the neuroectoderm and nonneural ectoderm to separate during embryogenesis. c. compensatory fluid accumulation following an in utero brain infarction (stroke). d. failure of the cerebellar vermis to form correctly during embryogenesis. 3. Proposed theories to explain progressive expansion of IACs in dogs include a. active secretion by the arachnoid cells lining the cyst cavity. b. movement of fluid into the cyst cavity along an osmotic pressure gradient. c. movement of fluid into the cyst from the neighboring subarachnoid space via slit-like openings (one-way valves) into the cyst lumen. d. all of the above

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4. Which is most characteristic of the typical signalment for dog with an IAC? a. 10-year-old female spayed German shepherd b. 4-year-old male castrated shih tzu c. 2-year-old female greyhound d. There is no typical signalment. 5. Clinical signs associated with IAC in dogs include a. abnormal mentation. b. generalized seizures. c. cerebellar dysfunction. d. all of the above 6. The preferred imaging modality for diagnosis of IAC in dogs is a. ultrasound. b. scintigraphy. c. magnetic resonance imaging. d. computed tomography. 7. The characteristic MRI appearance of an IAC in a dog is a large, welldemarcated, cyst-like structure that is a. hypointense on T1-weighted images. b. hyperintense on T2-weighted images. c. contrast-enhancing and hyperintense on FLAIR images. d. a and b 8. In a study of IAC cases in which brain

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compression by the cyst was measured, dogs were found to be most likely to exhibit clinical dysfunction if a. the cyst compressed more than 14% of the occipital lobe of the cerebrum. b. both the occipital lobe of the cerebrum and the cerebellum were compressed by the cyst. c. a and b d. none of the above 9. Medical therapy for IAC in dogs is directed at a. decreasing brain edema associated with the cyst. b. controlling seizure activity if present. c. minimizing increases in intracranial pressure. d. all of the above 10. Which statement regarding surgical management of IAC is false? a. Both cyst fenestration and cystoperitoneal shunting procedures have been described in dogs. b. Cystoperitoneal shunt (CPS) placement has been shown to be superior to fenestration in dogs and humans with IAC. c. The success rate for surgical management of IAC appears to be high in people and dogs. d. a and b

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Successful Use of Probiotics in a Dog with Chronic Diarrhea Teresa A. Bessler, DVM Buffalo Veterinary Clinic Buffalo, Wyoming

Patient: Kodi, a 14-year-old American Eskimo dog History: When Kodi became my patient in August 2007, he had a 2-year history of kidney disease and was eating Purina Veterinary Diets® NF Kidney Function® canine formula to help manage his condition. He also had a long history of frequent bouts of watery diarrhea. Therapy Plan: Because of Kodi’s chronic kidney disease, I instructed the owners to continue feeding NF. I also prescribed 1 g of sucralfate twice daily for 5 days to treat a brief episode of anorexia and 250 mg of metronidazole twice daily for 5 days to resolve the diarrhea; metronidazole helped briefly, but the diarrhea returned. In October 2007, Kodi’s owners made an appointment to have him euthanized because of the chronic diarrhea. Kodi was having fecal accidents in the house, and the owners did not wish to pursue expensive diagnostics. I talked to them about Purina Veterinary Diets® FortiFlora® Canine Nutritional Supplement, and they agreed to try it. Kodi was given FortiFlora once daily, and Purina Veterinary Diets ® Gentle Snackers TM were allowed as treats. Outcome: Two weeks after adding FortiFlora to the diet, Kodi’s diarrhea had transformed into fairly firm stools. FortiFlora helped resolve the problem. At Kodi’s last evaluation, the chronic diarrhea hadn’t returned. 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.

Veterinarian’s Comments I have been recommending Purina Veterinary Diets® FortiFlora® as a nutritional supplement for the past 2 years. I find it to be very effective in cases of acute and chronic diarrhea and in patients on long-term antibiotic therapy. I estimate that I have used FortiFlora in at least 40 patients with a 90% success rate. I explain to owners that FortiFlora is a nutritional supplement that contains beneficial bacteria and promotes intestinal health. Owners appreciate that FortiFlora comes in premeasured packages and is simply sprinkled on top of the pet’s food. FortiFlora delivers good clinical results, and dogs and cats find it palatable; I have not had one owner tell me that his or her pet would not eat it. Kodi’s owners were very happy with the positive results obtained with FortiFlora. They told me the nutritional supplement had changed their lives and Kodi’s as well, and they wished they had known about FortiFlora sooner. Sponsored by

Techniques for Laparoscopic and LaparoscopicAssisted Biopsy of Abdominal Organs ❯❯ Philipp Mayhew, BVM&S, MRCVS, DACVS Columbia River Veterinary Specialists Vancouver, Washington

At a Glance Patient Preparation and Positioning Page 171

Abdominal Access and Port Positioning Page 171

Liver Biopsy Page 171

Kidney Biopsy Page 173

Gastrointestinal Biopsy Page 173

Pancreatic Biopsy Page 175

Clinical Pearls Page 176

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Abstract: Multiorgan pathology is a common ﬁnding during the diagnostic work-up of complex medical diseases in small animals. Collection of cytologic or biopsy samples from several abdominal organs can give the clinician crucial information in guiding therapy. Although many modalities are available for sample collection, laparoscopic and laparoscopic-assisted techniques offer a minimally invasive approach for collection of high-quality biopsy samples from multiple organs during one anesthetic episode. This article discusses the laparoscopic approaches and techniques for multiorgan biopsy in cats and dogs.

iagnostic evaluation of many different disadvantages versus surgical biopsy techmedical conditions can be assisted by niques.4 Full-thickness intestinal biopsy obtaining biopsy samples from multiple samples cannot be harvested endoscopiabdominal organs. This sample collection has cally, and access to the lower small intestine is not possible with currently available traditionally been performed several ways. “Open” celiotomy has the advantage of endoscopic technology. Some studies allowing thorough inspection of, and easy have shown the limitations of endoscopiaccess to, all abdominal organs. However, it cally collected biopsy samples for diagnosis the most invasive technique, sometimes ing certain conditions (e.g., lymphoma).5,6 necessitating an incision from the xiphoid Flexible endoscopy does, however, have process to the pubis for access to the cranial the advantage of being an outpatient procedure, allowing direct visualization of and caudal abdominal structures. Ultrasound-guided ﬁne-needle aspiration mucosal lesions, and avoiding the reported or needle-core biopsy techniques can be 12% dehiscence rate of full-thickness surgiused for obtaining samples from the liver, cal biopsies.7 Laparoscopic procedures (performed pancreas, kidneys, and mesenteric lymph nodes.1–3 Ultrasound-guided techniques are entirely within the peritoneal cavity) and minimally invasive, but they require a skilled laparoscopic-assisted procedures (which use ultrasonographer, do not allow access to all laparoscopic manipulation to exteriorize organs areas of the peritoneal cavity, and have been for extraperitoneal surgery) can allow a thorshown to produce inferior samples in many ough evaluation of most abdominal organs. cases when compared with open surgical or It is not known whether laparoscopic exploration of the abdominal cavity can be as laparoscopic biopsy techniques.1–3 Flexible gastroscopy and small intestinal thorough as open exploration. However, endoscopy can be used for harvesting gas- almost all abdominal structures are visible tric and small intestinal biopsy samples.4–6 laparoscopically, and the success of laparoThese techniques have advantages and scopic exploration of the peritoneal cavity

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is limited only by the patience of the surgeon. port position depends on which techniques For example, laparoscopic examination of the are to be performed. In most cases, multiple full length of the bowel is possible but time organs can be accessed through a small numconsuming. Another important variable to con- ber of common instrument ports or one small sider is the reliability of preoperative abdomi- “assist” incision (an incision 2 to 4 cm in length nal imaging. In most cases, when preoperative created by enlargement of a previously placed imaging has identified the location of focal instrument port for exteriorization of abdomilesions or when diffuse disease only is sus- nal organs). Before beginning the procedure, pected, the need for laparoscopic visualization the surgeon should decide the minimum comof all organs is debatable. bination of instrument ports that will provide Compared with open celiotomy, a laparo- access to all organs to be biopsied. Usually, scopic approach has been shown to result in less two or three instrument ports are adequate. postoperative pain8 and a faster return to normal activity9 and may result in fewer and less severe Liver Biopsy wound-healing complications. This article pre- Due to its fi xed location and friable nature, sents some of the technical aspects of harvesting the liver is biopsied using totally laparoscopic biopsy samples using laparoscopic or laparo- techniques. When multiple organ biopsy samscopic-assisted techniques. These techniques ples are needed, the liver sample should be allow clinicians to offer their clients a high like- taken first so that if laparoscopic-assisted prolihood that, similar to open surgery, they will cedures are subsequently performed through obtain high-quality diagnostic samples from larger port incisions, it will not be necessary all the necessary organs during one procedure, to reestablish the pneumoperitoneum for liver when such an approach is clinically indicated. biopsy at the end of the procedure. However, In choosing which diagnostic techniques reinsufflation may be recommended if the surto use, clinicians must balance the desire to geon wishes to confirm adequate hemostasis obtain high-quality biopsy samples from all before completing the surgery. It is wise to the organs in which pathology is suspected in consider performing a full coagulation profile the least invasive way possible against own- before laparoscopic liver biopsy. I place a preers’ financial constraints and tolerance for the tied loop ligature (described below) in animals with coagulopathy or when harvesting large risk of potential complications. samples, although the need or benefit of this Patient Preparation and Positioning practice has not been evaluated scientifically. For all of the techniques described below, the In most cases, when a liver biopsy is perpatient is placed in dorsal recumbency and formed in isolation for diffuse hepatopathy, a sinthe abdomen is liberally clipped from 2 inches gle instrument port suffices. The port is placed cranial to the xiphoid process to the pubis. under direct visualization in a paramedian Laterally, the patient is clipped to approximately the midabdomen level as for a tradiTO LEARN MORE tional open celiotomy. It is important that wide clipping and aseptic preparation be performed in the unlikely event that conversion to an Patient preparation and the Hasson and Veress open procedure becomes necessary. Lateral needle techniques are described in more detail recumbency can be used for access to certain in the August 2008 Surgical Views article, individual organs, but when examination or “Canine Laparoscopic and Laparoscopic-Assisted biopsy of multiple organs is desired, I prefer Ovariohysterectomy and dorsal recumbency and the use of a subumbiliOvariectomy,” available cal telescope port. at CompendiumVet.com.

Abdominal Access and Port Positioning A subumbilical telescope port can be placed using either the Hasson or the Veress needle technique.10 For the following procedures, instrument

QuickNotes Before beginning the procedure, the surgeon should decide the minimum combination of instrument ports that will provide access to all organs to be biopsied.

A video demonstrating the Hasson technique is also available at CompendiumVet.com.

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A needle-core biopsy needle has been placed percutaneously and is inserted into the renal cortex before being discharged. The advantage of the laparoscopic approach is the ability to monitor hemorrhage after withdrawal of the instrument.

QuickNotes In all cases, liver biopsy sites should be visualized until the surgeon is convinced that all hemorrhage has ceased before removing the telescope.

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FIGURE 2

Courtesy of Dr. Mayhew

Courtesy of Philipp Mayhew, BVM&S, MRCVS, DACVS

FIGURE 1

Placement of the wound retraction device produces a small, protected, circular access incision into the peritoneal cavity.

position in either the right or left cranial quad- site with a vessel-sealing device has been rant of the abdomen. Care should be taken not shown in some studies to reduce hemorrhage to place the cannula cranial to the last rib, which associated with the procedure.11,12 Several samples can be taken from multiple risks entering the thoracic cavity and could precipitate pneumothorax. A 6-mm trocarâ&#x20AC;&#x201C;cannula lobes. By passing the telescope caudally or craassembly can be placed to accommodate 5-mm nially around the falciform fat, access to both cup biopsy forceps. A second port can be placed right and left sides of the liver is possible. If the on the contralateral side if the surgeon plans to surgeon judges that excessive hemorrhage is use a hemostatic device (vessel-sealing device occurring after liver biopsy, a piece of gelatin or ligature) to harvest the sample. If a focal liver sponge or oxidized regenerated cellulose can lesion has been diagnosed from preoperative be passed through a port and manipulated into imaging, the instrument port should be placed position at the biopsy site to promote clot foron the side of the focal lesion. If other laparo- mation and hemostasis. In all cases, the biopsy scopic procedures are to be performed in addi- sites should be visualized until the surgeon tion to the liver biopsy, the instrument ports is convinced that all hemorrhage has ceased used for those procedures can usually be used before removing the telescope. If hemorrhage is of concern (e.g., in anito access the liver, thus minimizing the number mals with advanced hepatic failure, focal or of necessary ports. The simplest way to perform a liver biopsy is highly vascular lesions, or known coagulopaby using 5-mm laparoscopic cup biopsy forceps thies), it may be preferable to apply a pretied to harvest pieces of liver from the edge of a lobe. loop ligature or extracorporeally assembled The tissue is grasped and gently twisted until it loop ligature to ligate the tip of the lobe separates from the rest of the lobe. Care should before taking biopsy samples. This ligation decreases the chance of severe be taken during this process hemorrhage; however, a secto avoid tearing liver parenSURGICAL ond port must be placed for chyma by rough handling, VIDEO application of the ligature. A which can lead to excessive modiďŹ ed Roeder laparoscopic hemorrhage. Performed corTo see videos of a laparoscopic slipknot is used. The loop rectly, this technique has liver biopsy using a 5-mm is passed through the instrubeen shown to cause minimal laparoscopic cup forceps, a ment cannula either with the bleeding in healthy dogs and gelatin sponge, and a pretied plastic application device (for to yield good-quality tissue loop ligature, visit commercial pretied loop ligasamples.11,12 Coagulation of CompendiumVet.com. the periphery of the biopsy tures [e.g., Endoloop, Ethicon

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Endosurgery, Cincinnati, OH] ) or with a knot pusher (for self-assembled loop ligatures). It must then be manipulated into position around the tip of a liver lobe. A blunt probe can aid in elevating the liver lobe during loop positioning. When the loop is in position, it is tied by advancing the plastic application device or knot pusher (for self-assembled loops) against the modiﬁed Roeder knot until it securely ligates the blood vessels and bile ducts within the parenchyma. The liver tissue distal to the ligature can then be cut with endoscissors and withdrawn through a cannula, or multiple bites can be taken with laparoscopic cup biopsy forceps. If a large focal liver mass is to be biopsied, extreme care should be taken because these lesions are often very vascular. Consideration should be given to taking a needle-core biopsy sample under laparoscopic guidance before collecting larger samples to gauge the level of hemorrhage that will result. Otherwise, a loop ligature should be used to harvest the sample to reduce the risk of profuse hemorrhage. It may be advisable to use a specimen retrieval bag to remove larger samples. Extension of the port site may be needed to recover these samples.

from the kidney and ensure that hemostasis has been achieved before closure. I prefer to use an automatic spring-activated needle-core biopsy needle to decrease the possibility of inadvertent premature needle withdrawal from the parenchyma that can occur from excessive movement with manually activated Tru-Cut needles. Under direct visualization, the biopsy needle is guided into the parenchyma and directed to pass across the renal cortex to maximize the number of glomeruli recovered13 (FIGURE 1). The sample is taken by activating the biopsy needle, which is subsequently withdrawn from the peritoneal cavity to recover the sample. Usually, one to two samples are taken from one or both kidneys, depending on the nature of the pathology suspected. If the needle is placed too deeply into the medulla, fewer glomeruli may be recovered and there is a greater risk of hemorrhage from arcuate vessels.13 The laparoscopic technique using a 14-gauge needle has been shown to give superior-quality biopsy samples compared with ultrasonographic guidance of the same-size needle.2

Gastrointestinal Biopsy Kidney Biopsy

Biopsies of the small intestine are usually If a single kidney is to be biopsied, a needle- performed using a laparoscopic-assisted techcore biopsy technique is usually selected. nique. In humans, in which the small intestiTheoretically, no instrument port is required nal lumen is significantly larger, endoscopic for this technique because the biopsy needle stapling devices can be used to resect small can be passed percutaneously into the perito- antimesenteric sections of small intestine. This neal cavity in a location directly ventral and would likely result in excessive compromise of somewhat caudal to the kidney. However, it the luminal diameter in small animals and so is is helpful to have one instrument port avail- not practical in these patients. Exteriorization able for passage of a blunt probe that can of bowel segments through a small assist incihelp manipulate the kidney into position for sion, followed by standard small intestinal the biopsy and place pressure on the biopsy biopsy sample collection from the antimessite after needle withdrawal to minimize hem- enteric border, is usually the best technique in orrhage from the site. This instrument port dogs and cats. can be placed on the ventral A technique for laparomidline 5 to 10 cm cranial scopic-assisted small intesSURGICAL or caudal to the telescope tinal biopsy that involves VIDEO port. If an instrument port is placement of a paramedian available, a piece of oxidized port lateral to the right rectus To see a video of a kidney regenerated cellulose can be abdominis muscle has been biopsy using a 14-gauge placed over the biopsy site reported.14 A 10-mm Babcock spring-loaded needle-core forceps is used to grasp a if hemorrhage is profuse. A biopsy needle and oxidized section of duodenum, jejusignificant benefit of laparosregenerated cellulose, visit num, or ileum and bring it copy is the ability to visualize CompendiumVet.com. to the port-site incision. The the amount of hemorrhage

QuickNotes A signiﬁcant beneﬁt of laparoscopy is the ability to visualize the amount of hemorrhage from the kidney and ensure that hemostasis has been achieved before closure.

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Large segments of small intestine can be removed through the laparoscopic-assisted incision. Using a wound retraction device minimizes pressure on the mesenteric root, preventing vascular engorgement of exteriorized bowel and facilitating its return to the peritoneal cavity after completion of the biopsy.

QuickNotes There are limitations to the use of small assist incisions for abdominal organ biopsy.

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Courtesy of Dr. Mayhew

FIGURE 4

Courtesy of Dr. Mayhew

FIGURE 3

The duodenum has been partially exteriorized through the assist incision. A biopsy sample can easily be harvested from the duodenum in addition to a pancreatic sample, if clinically indicated.

trocar–cannula assembly is removed while the device has several advantages. It prevents comBabcock forceps is still grasping the small intes- pression of the mesenteric root and subsequent tinal loop. To exteriorize the loop of intestine, vascular compromise compared with exteriorthe port incision can be enlarged to 2 to 4 cm, ization of the intestine through an unretracted as needed. A sample can then be harvested incision, thereby allowing large sections of in standard fashion. Using this technique, an intestine to be exteriorized for examination at enterostomy feeding tube can also be placed at any one time (FIGURE 3). It also allows other the time of biopsy, if clinically indicated.14 If a structures such as the pancreas and mesfeeding tube is to be placed, the section of the enteric lymph nodes to be elevated enough small intestine that is grasped must be chosen to easily collect biopsy samples (FIGURE 4). carefully because duodenostomy and jejunos- If the assist incision is directed cranially from tomy feeding tubes are usually placed in the the original subumbilical port location, it is midduodenal or proximal jejunal areas to opti- usually possible to obtain a sample from the stomach, although this may be challenging in mize nutritional absorption during feeding. I often use a modification of this technique large or deep-chested dogs. The wound retracto allow easier access to the small intestine and tion device also prevents contamination of the other organs. Once any laparoscopic procedures wound margin and has been shown in some (e.g., liver biopsy) are completed, the telescope human studies to decrease wound infection is removed from its subumbilical location and rates.15 Alternatives to the wound retractor the port incision enlarged to 3 to 4 cm to allow device include the placement of Gelpi retractors or a small Balfour retractor placement of a 2- to 4-cm in the wound to open the incilaparoscopic wound retracSURGICAL sion and decrease comprestor (Alexis Wound Retractor, VIDEO sion of the mesenteric root. Applied Medical Corp, Rancho There are limitations to the Santa Margarita, CA). Once the To see videos demonstrating use of small assist incisions retractor is in place, the circumthe placement of a wound for abdominal organ biopsy. ferential force exercised at the retractor and use of this It is difficult to exteriorize the wound margin holds open a device in exteriorizing a large proximal descending duodesmall circular orifice into the section of intestine, visit num and the ileocecocolic peritoneal cavity (FIGURE 2). CompendiumVet.com. This relatively inexpensive junction. The colon can be

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Once exteriorized, the small intestine can biopsied in standard fashion. The use of a small-gauge stay suture placed at the antimesenteric border, followed by an incision with a number 11 blade, helps in the atraumatic harvesting of small intestinal biopsy samples.

Courtesy of Dr. Mayhew

FIGURE 6

Courtesy of Dr. Mayhew

FIGURE 5

The laparoscopic-assisted technique allows local lavage to be performed in a location away from the opening into the peritoneal cavity, thus minimizing peritoneal contamination.

exteriorized, although full-thickness colonic abdominal incision site, thus preventing any biopsy is strongly discouraged because of the contamination of the peritoneal cavity with high morbidity associated with dehiscence in lavage solution (FIGURE 6). After completion of this area and the excellent diagnostic quality all procedures, all abdominal wall incision sites can be closed routinely. of colonoscopic biopsy samples.4 With either the modified or unmodified technique, once the intestine is exteriorized, Pancreatic Biopsy samples can be taken using a technique simi- A laparoscopic or laparoscopic-assisted lar to that used during open celiotomy. Using a (FIGURE 4) technique can be used for pancrestay suture of 4-0 suture material, a small, full- atic biopsy. A single instrument port can be thickness bite is placed on the antimesenteric used for the laparoscopic technique if a punch side of the intestine. A number 11 blade is used technique is used, although a second port is to incise the intestine around the stay suture, necessary if use of a vessel-sealing device or ensuring that an adequate sample of mucosa as ligature is desired. A second instrument port well as submucosa and muscularis is harvested may also be necessary if significant manipula(FIGURE 5). A skin biopsy punch can also be tion of the surrounding organs is needed to used for small intestinal biopsy sample col- obtain an unobstructed view of the pancreas. lection.16 The incision(s) can be closed using A pancreatic biopsy is usually performed in 3-0 or 4-0 monofilament absorbable suture addition to biopsy of other organs; therefore, material (e.g., polydioxanone) in a simple, access is usually from instrument ports posiinterrupted or simple, continuous suture pat- tioned for these other biopsy procedures. tern. If significant narrowThe tip of the right (duoing of the luminal diameter denal) limb of the pancreas SURGICAL is anticipated after suturing, is usually the simplest to VIDEO the incisions can be closed sample. Clinical judgment in transverse fashion to prewill help the surgeon deterserve the luminal diameter mine whether this area will To see a video of pancreatic as much as possible. After provide a representative sambiopsy using a 5-mm cup closure of the biopsy site is ple. A 5-mm cup biopsy forbiopsy forceps, visit complete, local lavage can ceps can be used to carefully CompendiumVet.com. be performed away from the remove a small piece of pan-

QuickNotes The tip of the right (duodenal) limb of the pancreas is usually the simplest to sample.

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Courtesy of Dr. Stephen J. Mehler, DVM, DACVS

FIGURE 7

Clinical Pearls Using a combination of laparoscopic and laparoscopic-assisted techniques, a “one-procedure” approach to collection of high-quality organ samples can be achieved in a minimally invasive fashion. Laparoscopic-assisted techniques can allow several organs to be biopsied through one small port incision.

A laparoscopic biopsy sample is being taken from the periphery of the right pancreatic limb using a 5-mm cup biopsy instrument.

creas from the periphery of the lobe (FIGURE 7). Care should be taken to avoid performing a biopsy on the body of the pancreas (to avoid damaging pancreatic ducts) or the area where the caudal pancreaticoduodenal vessels enter the tip of the right pancreatic limb. This technique has been shown to be safe in healthy dogs, with no significant clinical abnormalities detected postoperatively, although histologically some inflammation is seen around biopsy sites.17 To reduce hemorrhage, several other techniques can be used. A pretied loop ligature can be placed around a piece of pancreas to be biopsied, or hemostatic clips can be placed in a V-shape around the tissue segment to be excised. A vessel-sealing device can also be used to harvest the sample. A recent study compared use of the Harmonic Scalpel device (Ethicon Endosurgery Inc, Cincinnati, OH) with the placement of hemostatic clips to harvest pancreatic biopsy samples laparoscopically.11 The Harmonic Scalpel led to a reduction in hemorrhage but resulted in significantly greater inflammation.

When multiple organ biopsies are required, thought should be given to the optimal position of instrument ports to allow access to all organs in question while minimizing the total number of ports required. When taking a liver biopsy sample, it is my preference to use a loop ligature around the tip of the liver lobe in all animals that are known to have coagulopathy.

Conclusion Laparoscopic and laparoscopic-assisted techniques can be used in combination to gather samples from multiple abdominal organs when diagnostic work-up of complex multiorgan pathology is performed. Even though conversion to an open approach should always be discussed with the owners, in most cases laparoscopic techniques can offer a one-procedure approach for collection of high-quality biopsy samples from multiple organs that is less invasive than open celiotomy.

References 1. Cole TL, Center SA, Flood SN, et al. Diagnostic comparison of needle and wedge biopsy specimens of the liver in dogs and cats. JAVMA 2002;220:1483-1490. 2. Rawlings CA, Diamond H, Howerth EW, et al. Diagnostic quality of percutaneous kidney biopsy specimens obtained with laparoscopy versus ultrasound guidance in dogs. JAVMA 2003;223:317-321. 3. Wang KY, Panciera DL, Al-Rukibat RK, et al. Accuracy of ultrasound-guided ﬁne-needle aspiration of the liver and cytologic ﬁndings in dogs and cats: 97 cases (1990-2000). JAVMA 2004;224:75-78. 4. Mansell J, Willard MD. Biopsy of the gastrointestinal tract. Vet Clin North Am Small Anim Pract 2003;33:1099-1116.

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5. Willard MD, Lovering SL, Cohen ND, et al. Quality of tissue specimens obtained endoscopically from the duodenum of dogs and cats. JAVMA 2001;219:474-479. 6. Evans SE, Bonczynski JJ, Broussard JD, et al. Comparison of endoscopic and full-thickness biopsy specimens for diagnosis of inﬂammatory bowel disease and alimentary tract lymphoma in cats. JAVMA 2006; 229:1447-1450. 7. Shales CJ, Warren J, Anderson DM, et al. Complications following full-thickness small intestinal biopsy in 66 dogs: a retrospective study. J Small Anim Pract 2005;46:317-321. 8. Devitt CM, Cox RE, Hailey JJ. Duration, complications, stress and pain of open ovariohysterectomy versus a simple method

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of laparoscopic-assisted ovariohysterectomy in dogs. JAVMA 2005;227:921-927. 9. Culp WTN, Mayhew PD, Bown DC. The effect of laparoscopic versus open ovariectomy on post-surgical activity in small dogs. Proc Am Coll Vet Surg Annu Symp 2008. 10. Gower S, Mayhew PD. Canine laparoscopic and laparoscopicassisted ovariohysterectomy and ovariectomy. Compend Contin Educ Pract Vet 2008;30:430-440. 11. Barnes RF, Greenﬁeld CL, Schaeffer DJ, et al. Comparison of biopsy samples obtained using standard endoscopic instruments and the harmonic scalpel during laparoscopic and laparoscopicassisted surgery in normal dogs. Vet Surg 2006;35:243-251. 12. Vasanjee SC, Bubenik LJ, Hosgood G, et al. Evaluation of hemorrhage, sample size, and collateral damage for ﬁve hepatic biopsy methods in dogs. Vet Surg 2006;35:86-91. 13. Rawlings CA, Howerth EW. Obtaining quality biopsies of the liver and kidney. JAAHA 2004;40:352-358. 14. Rawlings CA, Howerth EW, Bement S, et al. Laparoscopic-assisted enterosotomy tube placement and full-thickness biopsy of the jejunum with serosal patching in dogs. Am J Vet Res 2002;63:1313-1319. 15. Horiuchi T, Tanishima H, Tamagawa K, et al. Randomized controlled investigation of the anti-infective properties of the Alexis retractor/protector of incision sites. J Trauma 2007;62:212-215. 16. Keats MM, Weeren R, Greenlee P, et al. Investigation of Keyes skin biopsy instrument for intestinal biopsy versus a standard biopsy technique. JAAHA 2004;40:405-410. 17. Harmoinen J, Saari S, Rinkinen M, et al. Evaluation of pancreatic forceps biopsy by laparoscopy in healthy beagles. Vet Ther 2002;3:31-36.

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! i !

If a dose is missed and a 30-day interval between dosing is exceeded, administer SENTINEL Flavor Tabs immediately and resume the monthly dosing schedule. Warnings: Not for use in humans. Keep this and all drugs out of the reach of children. Precautions: Do not use SENTINEL Flavor Tabs in puppies less than four weeks of age and less than two pounds of body weight. Prior to administration of SENTINEL Flavor Tabs, dogs should be tested for existing heartworm infections. Mild, transient hypersensitivity reactions manifested as labored respiration, vomiting, salivation, and lethargy have been noted in some treated dogs carrying a high number of circulating microﬁlariae.

NADA 141-084, Approved by FDA 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. Description: SENTINEL® (milbemycin oxime/lufenuron) Flavor Tabs® are available in four tablet sizes in color-coded packages for oral administration to dogs and puppies according to their weight. Milbemycin oxime consists of the oxime derivatives of 5-didehydromilbemycins in the ratio of approximately 80% A 4 (C32H45NO7, MW 555.71) and 20% A 3 (C31H43NO7, MW 541.68). Milbemycin oxime is classified as a macrocyclic anthelmintic. Lufenuron is a benzoylphenylurea derivative with the following chemical composition: N-[2,5-dichloro-4-(1,1,2,3,3,3, -hexafluoropropoxy)-phenylaminocarbonyl]-2,6- difluorobenzamide (C 17H 8CI2F 8N2O3, MW 511.15). Benzoylphenylurea compounds, including lufenuron, are classified as insect development inhibitors (IDIs). Indications and Usage: SENTINEL Flavor Tabs are indicated for use in dogs and puppies, four weeks of age and older, and two pounds body weight or greater. SENTINEL Flavor Tabs are also indicated for the prevention of heartworm disease caused by Dirofilaria immitis, for the prevention and control of flea populations, the control of adult Ancylostoma caninum (hookworm), and the removal and control of adult Toxocara canis and Toxascaris leonina (roundworm) and Trichuris vulpis (whipworm) infection. Lufenuron controls flea populations by preventing the development of flea eggs and does not kill adult fleas. Concurrent use of an adulticide product may be necessary for adequate control of adult fleas. Dosage and Administration: SENTINEL Flavor Tabs are given orally, once a month, at the recommended minimum dosage of 0.23 mg/lb (0.5 mg/kg) milbemycin oxime and 4.55 mg/lb (10mg/kg) lufenuron. Dogs over 100 lbs. are provided the appropriate combination of tablets.

Adverse Reactions: The following adverse reactions have been reported in dogs after giving milbemycin oxime or lufenuron: vomiting, depression/lethargy, pruritus, urticaria, diarrhea, anorexia, skin congestion, ataxia, convulsions, hypersalivation, and weakness. Efficacy: Milbemycin Oxime Milbemycin oxime provided complete protection against heartworm infection in both controlled laboratory and clinical trials. In laboratory studies, a single dose of milbemycin oxime at 0.5 mg/kg was effective in removing roundworm, hookworm, and whipworm. In well-controlled clinical trials, milbemycin oxime was also effective in removing roundworms and whipworms and in controlling hookworms. Efficacy: Lufenuron Lufenuron provided a 99% control of flea egg development for 32 days following a single dose of lufenuron at 10 mg/kg in studies using experimental flea infestations. In well-controlled clinical trials, when treatment with lufenuron tablets was initiated prior to the flea season, mean flea counts were lower in lufenuron-treated dogs versus placebo-treated dogs. After 6 monthly treatments, the mean number of fleas on lufenuron-treated dogs was approximately 4 compared to 230 on placebo-treated dogs. When treatment was initiated during the flea season, lufenuron tablets were effective in controlling flea infestations on dogs that completed the study. The mean flea count per lufenuron-treated dog was approximately 74 prior to treatment but had decreased to 4 after six monthly doses of lufenuron. A topical adulticide was used in the first eight weeks of the study to kill the pre-existing adult fleas.

SENTINEL Flavor Tabs are palatable and most dogs will consume the tablet when offered by the owner. As an alternative to direct dosing, the tablets can be hidden in food. Administer SENTINEL Flavor Tabs to dogs, immediately after or in conjunction with a normal meal. Food is essential for adequate absorption of lufenuron.

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

SENTINEL Flavor Tabs must be administered monthly, preferably on the same date each month. In geographic areas where mosquitoes and ﬂeas are seasonal, the treatment schedule should begin one month prior to the expected onset and should continue until the end of “mosquito and ﬂea season.” In areas with year-round infestations, treatment should continue through the entire year without interruption.

Manufactured for: Novartis Animal Health US, Inc. Greensboro, NC 27408, USA

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3 CE CREDITS

CE Article 2

Pancarpal and Partial Carpal Arthrodesis ❯❯ Nicole J. Buote, DVM The Animal Medical Center New York, New York

❯❯ Daryl McDonald, DVM, MS, DACVS ❯❯ Robert Radasch, DVM, MS, DACVSa The Dallas Veterinary Surgical Center Dallas, Texas

At a Glance Anatomy Page 180

Indications Page 182

General Principles of Arthrodesis Page 182

Preoperative Evaluation Page 184

Partial Carpal Versus Pancarpal Arthrodesis Page 185

Postoperative Management Page 189

Complications Page 190

a Dr. Radasch discloses that he has received financial support from IMEX Veterinary, Inc.

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Abstract: Arthrodesis can be an effective procedure to restore acceptable function and alleviate pain when other medical or surgical treatments are not possible. A thorough knowledge of carpal anatomy and strict adherence to the principles of arthrodesis are essential to success. The most important factor in determining whether a partial carpal arthrodesis can be performed is the stability of the antebrachiocarpal joint. Multiple techniques, including plating, pinning, and external skeletal fixation, have proven successful, and this article discusses these techniques and the complications of each.

rthrodesis—the surgical elimination of joint motion and, ultimately, bony fusion of joint surfaces—is considered a salvage procedure for patients in which other surgical or medical treatment will not restore normal, pain-free joint function.1–5 It can relieve pain and restore reasonable limb function. Ankylosis is the pathologic immobilization of a joint by a combination of osteophytosis, enthesiophytosis, intraarticular fibrosis, periarticular fibrosis, capsular adhesion, and musculotendinous contracture.5 Spontaneous ankylosis rarely results in bony fusion of a joint and often causes the joint to be painful. For certain joints, such as the hip, elbow, or stifle, total joint replacement or excision arthroplasty can be an alternative to arthrodesis. There have been reports of success with splinting or casting of dogs with minor hyperextension injuries; if the injury is severe, however, conservative treatment is unlikely to achieve functional results.6,7 In some patients, amputation may be the only feasible alternative to arthrodesis.2,4,5,8 The carpus and tarsus are the most common joints in which arthrodesis is performed in small animal patients.2–5 Despite some degree of gait alteration, the procedure typically results in a comfortable, functional limb. Currently, there are two broad categories of carpal

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arthrodesis: partial arthrodesis (the fusing of only the distal two joints) and pancarpal arthrodesis (the immobilization of all three carpal joints). This article reviews partial and pancarpal arthrodesis in dogs and cats.

Anatomy In both dogs and cats, the carpus has seven bones arranged in two rows, which creates three distinct joints (FIGURE 1). The first row consists of the radiocarpal, ulnar carpal, and accessory carpal bones. The accessory carpal bone articulates caudally with the ulnar carpal bone (FIGURE 2). The second row comprises four carpal bones (C1, C2, C3, and C4). The carpal joint has three levels and is classified as a hinged (ginglymus) joint. The most proximal joint is the antebrachiocarpal (ABC) or radiocarpal joint, where the radiocarpal and ulnar carpal bones articulate with the distal articular surfaces of the radius and ulna, respectively. The middle or intercarpal (MC) joint consists of the distal articular surfaces of the radiocarpal and ulnar carpal bones and the proximal articular surfaces of C1 through C4. The carpometacarpal (CM) joint is the most distal and is made up of the distal articular surfaces of C1 through C4 and the proximal articular surfaces of metacarpals one through five. The ABC joint does

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Pancarpal and Partial Carpal Arthrodesis CE not communicate with either of the other two joints, but the MC and CM joints communicate between the distal row of carpal bones.3,9 Soft tissue structures responsible for supporting the carpus include ligaments, tendons, the flexor retinaculum, and the palmar fibrocartilage (FIGURES 2 AND 3). The medial and lateral collateral ligaments consist of the short radial collateral ligament and short ulnar collateral ligament, respectively (FIGURE 1). The short radial ligament originates on the tubercle of the radius above the styloid process and inserts on the most medial aspect of the radiocarpal bone. The short ulnar ligament originates on the styloid process of the ulna and inserts on the ulnar carpal bone. Palmar support is provided by the flexor retinaculum proximally and the palmar fibrocartilage distally (FIGURE 3). Two accessory ligaments originate from the free end of the accessory carpal bone and insert onto the palmar surface of the fourth and fifth metacarpal bones. These two ligaments act as a stay apparatus (i.e., a system of ligaments and tendons acting in concert to stabilize a particular joint in a physiologic position with minimal muscular energy) to stabilize the carpus. The only tendon significant to carpal stability in extension is the flexor carpi ulnaris, which originates on the caudomedial surface of the olecranon and the medial epicondyle of the humerus and inserts on the accessory carpal bone.3,5,10 In dogs and cats, each forelimb carries approximately 30% of the weight during a normal stride.11,12 This weight bearing, combined with high-impact forces from running, jumping, or trauma, can predispose the carpus to hyperextension injuries. Flexion and extension in the carpus are primarily at the ABC joint and, to a lesser degree, the MC joint. The relative contribution of the ABC, MC, and CM joints to carpal range of motion is 85% to 90%, 10% to 15%, and 0%, respectively.5,10 The normal range of flexion is approximately 100° for the ABC joint, 40° for the MC joint, and 10° for the CM joint.5 The normal standing angle of the carpus is approximately 140° to 180° in dogs and 160° to 180° in cats. One study revealed a significant difference in the metacarpophalangeal joint angle when the contralateral limb was elevated, with the angle becoming more acute under increased load.13 However, variation exists between breeds and individuals.

FIGURE 1

Bones and ligaments of the left forepaw, dorsal aspect. C1–C4 = first, second, third, and fourth carpal bones; CR = radiocarpal bone; CU = ulnar carpal bone; I–V = metacarpals; lig = ligament. (Reprinted with permission from Evans HE, ed. Miller’s Anatomy of the Dog. 3rd ed. Philadelphia: WB Saunders; 1993:240.)

FIGURE 2

Bones and ligaments of the forepaw, lateral aspect. CA = accessory carpal bone; lig = ligament; V = fifth metacarpal bone. (Reprinted with permission from Evans HE, ed. Miller’s Anatomy of the Dog. 3rd ed. Philadelphia: WB Saunders; 1993:242.)

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Indications The most common indications for carpal arthrodesis are ligamentous injuries, carpal bone fracture, and carpal joint luxations or subluxations5,10,14–17 (FIGURE 4). Hyperextension of the carpus, which can result from either acute trauma or repetitive chronic trauma, often damages the palmar ligaments and palmar carpal ﬁbrocartilage, leading to instability of one or more joints within the carpus6,8,18,19 (FIGURE 5). Shearing injuries to the medial or lateral collateral ligaments or carpal bones often cause substantial carpal instability and subsequent osteoarthritis.2,3,20 Other potential indications for carpal arthrodesis include: Carpal joint instability due to loss of articular cartilage or injury to supporting ligamentous structures, such as that associated with erosive and nonerosive immune-mediated joint disease and septic or fungal arthritis21–23 Chronic osteoarthritis that is nonresponsive to medical management24 Loss of carpal bones or supporting ligamentous structures due to resection of neoplastic conditions25 Congenital malformations of the carpus FIGURE 3

Superﬁcial ligaments of the left carpus, palmar aspect. (Reprinted with permission from Evans HE, ed. Miller’s Anatomy of the Dog. 3rd ed. Philadelphia: WB Saunders; 1993:239.)

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resulting in luxations or complete or partial agenesis of carpal bones26–28 Carpal arthrodesis may also be used in patients with high radial nerve injury; however, arthrodesis is not recommended in patients that have lost cutaneous sensation in the palmar region because of the potential for self-mutilation.2–5,10

General Principles of Arthrodesis To successfully achieve partial or complete arthrodesis of the carpus, the following basic surgical principles must be strictly observed: Remove articular cartilage from all bones of the joint(s) to be fused. This is generally accomplished with a pneumatic bur or rongeur (FIGURE 6). Drilling multiple small holes into the subchondral bone of the joints to be fused is called forage, which may help stimulate early joint fusion by providing vascular access channels and additional blood supply to the newly forming bone5 (FIGURE 7). Place the joints being fused into a normal standing angle before rigid stabilization is applied. Achieving the proper fusion angle is of paramount importance; the angle is FIGURE 4

Lateral radiograph of a carpus showing an obvious antebrachiocarpal luxation.

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Pancarpal and Partial Carpal Arthrodesis CE measured on the contralateral limb while the dog or cat is standing but may need to be modified if arthrodesis is expected to shorten the limb. The more obtuse the angle is, the straighter and longer the limb will be after surgery; conversely, the more acute the angle, the shorter the limb length. In most cases, the fusion angle is slightly less (i.e., closer to 0°) than the contralateral normal angle to make up for loss of cartilage and bone. The angle most commonly used to contour the plate for a pancarpal arthrodesis is 10° to 15° of hyperextension.13 Cut contact surfaces flat to produce the proper angle and increase bone contact. Unlike the stifle, the carpus is a congruent joint and does not require resection of bone end plates. As a result, carpal arthrodesis does not typically result in substantial limb shortening. Provide rigid stabilization of the joints to be fused, using plates or screws, internal pins and wires, tension bands, ring fi xators, or external skeletal fi xation (ESF) frames. Often, postoperative external coaptation is used as an adjunct to internal implants to reduce the risk of implant failure. Fixation must be rigid, and compression is preferred. Plates are most commonly used for their superior stability. Use of lag screws and Kirschner wires as the sole method of fi xation is not recommended because these devices are more flexible than plates and not as well secured to bone on each side of the arthrodesis, leading to frequent failure and breakage.1,2,10 Autogenous or allogenic cancellous bone graft material is inserted into the joints being fused to enhance bone formation and shorten healing time.2 Cancellous bone grafts promote bone formation by three mechanisms29,30:

FIGURE 5

Photograph of the lateral aspect of the left forepaw in a greyhound with acute onset hyperextension injury after jumping down from a car. FIGURE 6

Photograph of pneumatic bur removing articular cartilage from the surface of the radial carpal bone. FIGURE 7

Osteogenesis, the direct introduction of osteoblasts and osteogenic precursor cells Osteoinduction, the release of growth factors that induce osteogenic differentiation in mesenchymal tissue to produce bone Osteoconduction, the physical presence of the cancellous bone trabeculae, which acts as a scaffold for blood vessels and osteogenic cells to produce bone Osteogenesis occurs if an autogenous graft is used, whereas osteoconduction and osteoin-

Photograph after forage of the radial carpal bone created by a 1.5-mm drill bit.

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duction occur with both autogenic and allogenic grafts. Occasionally, a cortical bone onlay or inlay graft from a rib or the ilium or a commercial allograft can be used. Onlay or inlay cortical grafts are generally indicated only in patients with substantial loss of a portion of the carpal bones and are primarily useful for osteoconduction.

Preoperative Evaluation Presurgical evaluation is very important for proper case selection. To determine which type of ﬁ xation (partial or pancarpal arthrodesis) is best for a patient, the desired postoperative activity level for both long-term use and durBOX 1

Radiographic Findings Associated with Hyperextension Injuries10 Antebrachiocarpal joint An increased angle of extension is seen on a stressed lateral view. With chronic antebrachiocarpal injuries, radiographs show wearing of the palmar edge of the distal radius due to subluxation of the proximal carpal bones. Middle carpal joint A gap can be seen between the palmar process of the ulnar carpal bone and the base of metacarpal 5; the caudal aspect of the accessory carpal bone appears tipped up (evidence of subluxation and proximal angulation). With chronic middle or intercarpal joint injuries, radiographs show radiocarpal and ulnar carpal bones pivoted in a distopalmar direction; the dorsodistal edges come to rest on the base of the metacarpals, creating a wide gap between the craniodorsal surface of the radius and the radiocarpal bone. Instability at the middle carpal joint with a loss of integrity of accessory carpal bone ligaments leads to a widening of the space between the palmar process of the ulnar carpal bone and the base of the ﬁfth metacarpal, and the accessory carpal bone deviates dorsally. Carpometacarpal joint The bases of the metacarpal bones appear to overlap the carpal bones. Instability at the carpometacarpal joint may lead to the proximal carpal bones overriding the distal row. Accessory carpal joint Instability of this joint allows increased extension without altering the relationships of the carpal and middle or intercarpal bones. If ligaments from the accessory carpal bone to the fourth and ﬁfth metacarpals are injured, radiographs show a movement of the caudal aspect of the accessory carpal bone proximally, approaching a parallel position with the ulna. Lateral subluxation of the accessory carpal bone with mild carpal hyperextension has been reported in one dog and was treated with one lag screw into the ulnar carpal bone.

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ing the convalescent period must be identified. Owners must be made aware of the potential changes in gait and agility associated with the procedure. The type of injury also plays a major role in selecting the appropriate fi xation type. For example, ESF is preferred over internal fi xation for an open fracture, shearing wound, or septic joint because of the contamination associated with such conditions. Another important consideration is the condition of the other limbs and joints. Ideally, the rest of the involved limb and adjacent joints should be functional and able to compensate for increased stress. Eward and colleagues11 evaluated the effects of carpal range of motion restriction on gait analysis and found significant differences in the angle displacement of the ipsilateral shoulder and contralateral stifle, which suggests that the effect on surrounding joints may be an important consideration for arthrodesis candidates, especially those with concurrent diseases (e.g., arthritis, muscle atrophy). Preoperative blood work to assess the overall health of the animal is always advisable before inducing anesthesia. Culture of synovial fluid from suspected septic joints or open wounds is critical, although initial cultures have a 50% false-negative rate.31 Cytology of joint fluid and tests for antinuclear antibody or rheumatoid factor should be conducted if immune-mediated disease is suspected.17 Because most flexion and extension occurs at the ABC joint, obtaining properly positioned stress radiographs before performing a partial carpal arthrodesis is very important (BOX 1; FIGURES 8 AND 9). In some patients, however, stress radiographs may not reveal damage involving the ABC joint, and hyperextension becomes apparent only after distal fusion has been performed.2,5 Radiographs are also very helpful in planning the surgical procedure. Radiographs of the BOX 2

Distribution Rates of Hyperextension Injuries10

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Antebrachiocarpal joint: 10% Middle carpal joint: 28% Carpometacarpal joint: 46% Middle carpal and carpometacarpal joints: 16%

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Pancarpal and Partial Carpal Arthrodesis CE affected limb, taken with the carpus stressed in hyperextension, are necessary to determine the location and extent of ligament damage (FIGURE 9). Standard orthogonal views and medial, lateral, and palmar stressed views are indicated. One source states that standing lateral radiographs are the most effective at highlighting the injury but might not be possible because of the size or demeanor of some patients.3 Radiographs of the normal limb, ideally in a standing position, are used to determine the desired position in which the affected joint is to be fused and can be referred to during surgery. The angle of fusion should be carefully considered in all three planes: the angle of extension or ﬂexion, degree of varus or valgus, and proper rotational or axial alignment.5 Many techniques can be used to measure the proper joint angles, and ranges of normal joint angles have been published.2–5,10 Some surgeons bend a metal template into the proper angle by measuring it against the contralateral limb; the template is then sterilized and

used for comparison during surgery.5,10 Others take measurements with a goniometer, which is then sterilized. Although radiography is the most common imaging modality for diagnosis of carpal instability, other modalities, such as computed tomography, magnetic resonance imaging, and nuclear scintigraphy, may help classify bony injuries to the carpus when radiographs or clinical signs are unclear. With nuclear scintigraphy, an obvious uptake of the radiolabeled material in the carpal bones indicates a nonspeciﬁc positive result for injury or increased bone activity at the site from causes such as infection, arthritis, or neoplasia.17

Partial Carpal Versus Pancarpal Arthrodesis The decision to perform a partial or pancarpal arthrodesis primarily depends on the joint(s) involved, the type of injury, and the owner’s willingness to participate in postoperative care.

FIGURE 9

FIGURE 8

Lateral radiograph of a ﬂexed view showing increased joint spaces at both the ABC and MC joints.

Stressed lateral radiograph of the left carpus. Note the osteoarthritis at the MC and CM joints as well as a small gap at the ABC joint. The syringe case used to hyperextend the distal forepaw is visible at the bottom of the radiograph.

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Indications Partial Carpal Arthrodesis

QuickNotes Stress radiographs are very important in deciding which method of arthrodesis (partial or pancarpal) is appropriate for the patient.

Partial carpal arthrodesis fuses the MC and CM joints. Because the ABC joint is responsible for 85% to 90% of the carpal range of motion, preserving the ABC joint is highly desirable if the joint is normal. Fortunately, approximately 90% of all hyperextension injuries involve the MC and/or CM joint (BOX 2). Other indications for partial carpal arthrodesis include luxation or fracture of the MC or CM joints. Such injuries often cause damage to the ligamentous structures of the accessory carpal bone, which can be stabilized with wires and screws. Any injury to the accessory carpal bone or ligaments must be treated to reestablish stability; otherwise, the fusion may fail secondary to breakdown at the ABC joint. Stability will be preserved as long as the ligaments between the base of the accessory carpal, ulnar carpal, and ﬁfth metacarpal bones are intact. One study of partial carpal arthrodesis in dogs reported that 100% of owners were pleased with the function of the treated limb 32 months after surgery; some degree of hyperextension remained in 11% of the cases, and degenerative joint disease was identiﬁed on radiographs in 15.5% of the cases, but no dog required sub-

FIGURE 10 Orthogonal views of pancarpal arthrodesis done by plating. Note the specialized plate and the screw placement (four screws are placed in the radius, one in the radial carpal bone, and four in the third metacarpal bone).

sequent pancarpal arthrodesis.32 A 1991 study reported that only 50% of partial arthrodesis cases regained full limb function with plate ﬁ xation. The major complication cited was residual lameness due to interference with motion in the ABC joint from straight dynamic compression plates.33 A partial arthrodesis of just the ABC joint has been reported but is not recommended because the stresses placed on the MC and CM joints predisposes them to increased laxity and degenerative joint disease.34

Pancarpal Arthrodesis If ABC joint stability and function are concerns, a pancarpal arthrodesis may be performed to reduce the risk for future problems. Pancarpal arthrodesis essentially eliminates all movement in the carpus and, depending on the angle of fusion, may lead to a pronounced circumduction of the lower limb in the swing phase of the gait and during the walk or trot. The stride phase can be noticeably shortened.8 In one study of pancarpal arthrodesis, 97% of owners reported an improvement in gait and 74% reported normal use of the affected limb.35 Complications associated with straight plates, such as metacarpal fractures or broken or loose implants, have led to the development of specialized plates (2.7-mm/3.5-mm hybrid dynamic compression plates; Jorgensen Laboratories, Loveland, Colorado) for pancarpal arthrodesis; the plates are designed for smaller screws to be used over the metacarpal bones and larger screws to be used proximally to decrease the risk for iatrogenic fracture2,36,37 (FIGURE 10). Current recommendations are to use a screw with a diameter no larger than 40% the width of the bone.2 The screw holes of these plates are also located to conform to the canine carpus, with a central hole that can accommodate a screw of either size positioned over the radiocarpal bone. The plates are also bent at 5° to decrease the need for contouring and were shown in a recent study to attain an 8.1% increase in mean bending strength compared with a basic 3.5-mm dynamic compression plate.38 Veterinary cuttable plates have also been used for pancarpal arthrodesis with a good clinical outcome.39

Surgical Procedures Dorsopalmar view.

186

Lateral view.

Craniocaudal bending is the most signiﬁcant force leading to potential disruption of arthro-

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Pancarpal and Partial Carpal Arthrodesis CE desis. Ideally, plates should be placed on the tension (convex) side of the joint or bone to decrease the risk for plate failure.2,5,10 A plate applied to the compression (concave) side absorbs most of the bending load, and the bone absorbs almost none. As such, the plate must be stiffer than the bone and well secured to resist failure. During normal weight bearing, a tension surface plate produces interfragmentary compression and the plate is loaded in tension. Plates tolerate tensile loads very well and are relatively resistant to cyclic failure. Plates placed on the compression surface are subject to cyclic bending forces, which lead to fatigue failure because most weight bearing is on the plate, not the bone. Although placement on the tension side would be ideal, most plates are placed on the compression side because the surgical approach is much easier and iatrogenic damage to vital structures is less likely.

Partial Carpal Arthrodesis A common technique for partial carpal arthrodesis uses a T plate extending from the radiocarpal bone onto the third metacarpal bone with the cross of the T positioned proximally (FIGURE 11), which provides stable ﬁ xation for distal fusions. Despite decreased range of motion in the ABC joint, the long-term results in one study were satisfactory.40 T plates can be used for distal joint fusion, but care must be taken because they can impinge on the dorsal surface of the radius during extension, causing pain and lameness. Plate removal after fusion might reduce these problems. Three other techniques are used: Cross pins are placed, starting in the second and fourth metacarpal bones and seated into the radiocarpal and ulnar carpal bones rather than the radius (FIGURE 12). Haburjak and associates37 reported that this technique was easy to perform and allowed for latitude in pin placement. In their study, nine of 23 carpi had less-than-ideal positioning of the implants after surgery, but only one patient developed unsatisfactory results. Bandage-related complications and implant migration rates were approximately 30% but were not directly related to premature loss of stability.33 Multiple small pins are driven proximally from the second, third, and fourth metacarpal bones via the metacarpophalangeal joints

or slots in the metacarpals and across the MC joint into the carpal bones. The carpus is ﬂexed to 90° when reducing the MC and CM joints as the pins are seated. A circular or linear ESF frame is secured by placing a pin and/or wire in the radiocarpal bone and base of the metacarpal bones. A ring at the distal radius is sometimes placed to give added security to the construct but does not fuse the ABC joint.

Pancarpal Arthrodesis Although rigid ﬁ xation is recommended for all types of carpal fusion to provide stability and reduce complications, it is particularly necessary with pancarpal arthrodesis. The cranial or dorsal surface of the joint is most commonly plated because of the ease of the approach, even though this puts the plate on the compression side of the limb (FIGURE 10). Three to four screws are placed in the radius, one in the radiocarpal bone, and three to four in the third metacarpal bone. The disadvantages of this technique are its reliance on bone purchase in only one MC bone and the risk for metacarpal fracture. In large breeds, two cranial plates can be applied.2,5,10

QuickNotes Plates tolerate tensile loads very well and are relatively resistant to cyclic failure.

FIGURE 11 Orthogonal radiographs of a partial carpal arthrodesis done with a T-plate. The horizontal bar of the plate is positioned over the radiocarpal bone, and the vertical bar is secured to the third metacarpal bone.

Dorsopalmar view.

Lateral view.

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Husle41 described a plate-rod technique in which a plate is applied and cross pins are placed from the metacarpals to the radius. The plate is bent to provide 10° to 15° of extension to mimic or achieve a normal standing angle. Leaving the plate straight causes excessive stress on the metacarpophalangeal joints.2,5 A dynamic compression plate has the advantage of providing compression between screw holes and between multiple joint surfaces. Radiographic evidence of healing is often noted as early as 4 to 5 weeks after surgery.42 The use of a medial plate technique has also been reported.43 The advantages include excellent purchase for distal screws through multiple metacarpal bones as well as greater biomechanical strength. Excision of the ﬁrst phalanx may be necessary but is not difﬁcult; however, contouring the plate to obtain the proper angle and alignment can be very challenging. To some extent, the degree of hyperextension is obtained by adjusting the position of the plate on the bones and the contour of the proximal aspect of the plate along the medial aspect of the distal radius. From a biomechanical viewpoint, applying the plate on the palmar surface of the joint is the most desirable, but the extensive soft tissue dissection required makes this method

difficult. The technique was outlined in 1982 by Chambers and Bjorling,44 who at the time did not believe the approach was too challenging. Deep dissection, including transection of the flexor retinaculum, tendons of the deep digital flexor tendon, and flexor carpi radialis, is performed. The plate needs to accommodate a gradual bend of approximately 15° to 20°, and the plate width and screw size are dictated by patient size. Although this technique does require a longer surgical time, the authors concluded that the advantage of a biomechanically stronger implant outweighed the disadvantages.44 This technique has not gained wide acceptance even though the most common complications with arthrodesis are implant failure and nonunion. Linear ESF has been used for arthrodesis for many years. Although linear ESF techniques are primarily recommended in cases of severe trauma with bone loss and open or infected joints, they can be used in patients without such injuries.20,45 Many types of frames (e.g., Kirschner–Ehmer, Securos, acrylic) are used for linear ESF. In one study, an acrylic frame was shown to be mechanically superior to a Kirschner–Ehmer frame for compression and shear loads and to be equally strong for torsion loads; acrylic frames have the added advantage of uncomplicated application for FIGURE 12 smaller patients.46 A newer technique using circular ESF for arthrodesis has also been reported. In this technique, two wires per ring are placed in a closed fashion. Care must be taken to route the wires through a safe corridor, without passing them through large muscle bodies or neurovascular structures. Typical pin/ wire placement includes the mid and distal radius, across the proximal aspects of the metacarpals, and more distally in the bodies of the metacarpals (FIGURE 13). A noted disadvantage is difficulty in attaining the proper angle of extension. One study reports that the amount of stiffness and maximum load to failure did not differ significantly between ESF and a dynamic compression plate.36 However, failure with plates was typically fracture of the third metacarpal bone, while failure with ESF was seen with deformation of the Kirschner wires.36 Some authors Dorsopalmar view of partial carpal arthrodbelieve that ESF is advantageous because of esis done with cross pins. The cross pins start in the less invasive approach, the avoidance the second and fifth metacarpal bones and emerge of bandage or splint complications, and the from the carpal bones.

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Pancarpal and Partial Carpal Arthrodesis CE absence of the need to remove implants at a much later date.47 The most common complications of ESF are pin loosening and pin tract infections; however, fractures and sequestra have been reported, and owners need to be prepared for the postoperative home care. One study cites 100% success in pancarpal fusion using circular ESF in 10 limbs.47 As noted, achieving the proper angle of fusion can be challenging, and these dogs had a more acute angle of fusion. This is partly related to the principles of external ﬁxation, which dictate that the desired position of the limb lie eccentrically within the ring. The average time to healing was 12 weeks, similar to that for plating techniques, and the morbidity associated with a limited approach to the carpus was much lower. An important part of ESF is the lack of external coaptation, which decreases not only the cost to the owner (i.e., frequent bandage changes) but also the possible complications (e.g., bandage sores, muscle atrophy).47

Postoperative Management Arthrodesis is an extensive, invasive surgery that causes more soft tissue trauma than typical internal fixation and results in more inflammation. As such, significant postoperative swelling and compromised circulatory drainage of the distal limb are possible. A coaptation bandage is typically applied to these patients immediately after surgery. The bandage is changed as swelling decreases; ultimately, a long-term splint is applied if plates or pins were used for stabilization. When using ESF, a large, soft, padded bandage with absorbent sponges packed between the skin and the construct is applied immediately after surgery. This bandage is changed in a few days if strikethrough is present and then left on for approximately 1 week. The bandage is then downsized to a “bumper bandage” (covering just the rings or bars) and changed weekly. Radiographs are taken immediately after surgery to allow assessment of the angle and alignment of the joint and implant. Repeat radiographs are taken every 6 to 8 weeks to assess healing until bony fusion is complete. The pattern of osseous union within the joint spaces is influenced by the method of articular cartilage removal, width of the maintained surfaces, placement of bone graft, and presence of any remnants of dense subchondral bone plate. In the first 4 to 8 weeks after surgery, the

opacity of the joint spaces progressively and uniformly increases as the spaces are bridged by new bone trabeculae in response to the bone graft. Radiographic healing slows after 9 weeks, according to one source, because of stress protection by the plate, which is one indication for plate removal.42 During this time, the dense subchondral bone is resorbed and remodeled, but complete remodeling may take 6 to 12 months. Over time, cancellous bone adjacent to the metaphysis becomes continuous with that bridging the arthrodesis. If healing is disturbed, delayed, or arrested, the joint space remains radiolucent. There will be widening of the joint space if any instability develops before complete healing because of resorption of the newly formed bridging bone. Most arthrodeses heal with minimal callus around the periphery of the joint (unless callus was present at the time of surgery or extensive bone grafts were used). This lack of callus seems related to the stable ﬁxation methods used and the normal absence of periosteum at these joints. A study investigating healing after dorsal pancarpal arthrodesis revealed that neither sex, age, body weight, nor immediate versus delayed surgery had any inﬂuence on healing.42 Owners can usually expect partial weight

QuickNotes External skeletal ﬁxation is an excellent technique to use in cases of shear or open wounds.

FIGURE 13 Orthogonal views of pancarpal arthrodesis done with circular ESF.

Dorsopalmar view.

Lateral view.

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bearing after 1 to 2 weeks and full weight bearing by 2 to 4 months. At no time during the healing process should instability be detected. One recent study reported that as many as 83% of working dogs were able to return to most of their former duties after unilateral pancarpal arthrodesis ﬁ xation.48 Exercise restriction is extremely important in the immediate postoperative period (6 to 8 weeks or until bony healing is conﬁrmed) because any unregulated activity will subject the tissue to undue strain and could lead to early implant failure or loosening. ESF frames require more attention by owners. Daily pin tract cleaning and hydrotherapy are helpful to decrease morbidity associated with these implants.

Complications

QuickNotes Most postoperative complications are associated with technical errors in implant size or placement, activity level, or insufﬁcient coaptation.

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When dealing with a low-motion joint like the carpus, limb function is usually excellent after surgery and dogs can be expected to resume such activities as running and jumping.1,5 Even some working dogs have been able to return to duty after the requisite healing period. The principal features of a failed arthrodesis include continued lameness, continued instability at the joint, widening of the joint space(s) on radiographs, sclerosis of metaphyseal bone, and loose or broken implants. The most serious complication is a nonunion accompanied by failure of the implants with or without a septic joint.1,2,5,10 Two important causes of nonunion or malunion are incomplete removal of articular cartilage and the lack of an autogenous or allogenic bone graft.2,5,10 Failure to use bone grafts increases healing time, which makes the joint more vulnerable to instability8 and makes premature implant loosening and failure more likely.5,29 The insertion of a graft decreases the time to fusion by 4 to 8 weeks. Inadequate reduction of adjacent bones can lead to poor bone-to-bone contact, which slows healing. Failure to achieve a complete osseous union results in an unstable joint and painful ankylosis. Another common complication is bandage or cast sores leading to abraded skin, possible infection, and pain. Owners must ensure that the bandage stays clean and dry. Bandages should be changed every 10 to 14 days (more often if the bandage becomes wet or soiled or slips), and frequent bandage changes can become costly. This complication is the primary

reason some surgeons prefer ESF techniques. Diaphyseal fractures are another possible complication, especially with pancarpal arthrodesis. The ends of a plate can also act as stress risers—the abrupt change in material stiffness further increases the risk for fracture. Metacarpal bone fractures at the distal end of the plate are seen in a small percentage (9.4%) of patients with pancarpal arthrodesis, especially if the plate extends only a short distance onto the metacarpal bone. Recommendations currently are that the plate cover at least 50% of the length of the third metacarpal bone and that screw width not exceed 40% of the bone diameter.49 Implant loosening or breakage can be the result of technical errors in implant placement or size, unrestricted activity, or insufﬁcient external coaptation.50 Late implant loosening, leading to pain, lameness, or intermittently discharging sinuses, usually happens approximately 6 months after surgery. Other complications include failure of arthrodesis due to infection and misalignment of joints and implants due to improper angle of fusion. Irritation of the extensor tendons or other overlying soft tissue by a plate can also lead to morbidity because of the minimal soft tissue covering available in these locations.51 All these complications are acceptable reasons to remove plates or other implants after healing is complete.

Conclusion Carpal injuries, especially those caused by motor vehicle accidents and falls from heights, are common in companion animals. According to one source, both pancarpal and partial carpal arthrodesis provided excellent limb function in 80% of cases when used for hyperextension injuries, and the remaining 20% were substantially improved with varying degrees of limb dysfunction.3 Although some argue that pancarpal arthrodesis can be used for any indication, partial carpal fusion techniques have been proven reliable when the ABC joint is unaffected, which is in approximately 90% of cases.10,33 A study by Denny and Barr33 documented return of full limb function in only 50% of cases treated by partial carpal arthrodesis. One study showed good results for partial arthrodesis 32 months after surgery, with 100% of owners pleased with their

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Pancarpal and Partial Carpal Arthrodesis CE pet’s function. There was still some degree of hyperextension in 11% of cases, and degenerative joint disease was identiﬁed on radiographs in 15.5% of cases, but no further surgery was necessary.32 Partial carpal arthrodesis has the beneﬁt of allowing almost normal motion in the carpus. Pancarpal arthrodesis is used more often than partial carpal arthrodesis; even though motion in the carpus is eliminated, reasonable function of the limb remains. Many techniques have been discussed. In one study of pan-

carpal arthrodesis, 97% of owners reported improvement in gait and 74% reported normal use of the affected limb.35 Another study found no presence of lameness during a 6- to 12-month follow-up period and reported that the complication rate was low.47 Arthrodesis is an excellent surgical option for injuries involving the carpus and allows reasonable function of affected limbs with proper presurgical planning and postoperative management.

References 1. Moore RW, Withrow SJ. Arthrodesis. Compend Contin Educ Pract Vet 1981;3(4):319-330. 2. Lesser AS. Arthrodesis. In: Slatter D, ed. Textbook of Small Animal Surgery. Philadelphia: Saunders; 2003:2170-2180. 3. Diseases of the joints. In: Fossum TW, ed. Small Animal Surgery. St. Louis: Mosby; 2002:1023-1157. 4. Arthrology. In: Bojrab MJ, ed. Current Techniques in Small Animal Surgery. Philadelphia: Lea & Febiger; 1990:705-776. 5. Johnson KA. Arthrodesis. In: Olmstead ML, ed. Small Animal Orthopedics. St. Louis: Mosby; 1995:503-529. 6. Earley T. Canine carpal ligament injuries. Vet Clin North Am Small Anim Pract 1978;8(2):183-199. 7. Gambardella PC, Grifﬁths RC. Treatment of hyperextension injuries of the canine carpus. Compend Contin Educ Pract Vet 1982;4(2):127-131. 8. Johnson KA, Bellenger CR. The effects of autologous bone grafting on bone healing after carpal arthrodesis in the dog. Vet Rec 1980;107:126-132. 9. Ligaments and joints of the thoracic limb. In: Evans HE, ed. Miller’s Anatomy of the Dog. Philadelphia: WB Saunders; 1993:233-244. 10. Piermattei DL, Flo GL. Fractures and other orthopedic conditions of the carpus, metacarpus and phalanges. In: Piermattei DL, Flo GL, eds. Brinker, Piermattei and Flo’s Handbook of Small Animal Orthopedics and Fracture Repair. Philadelphia: WB Saunders; 1997:344-389. 11. Eward C, Gillette R, Eward W. Effects of unilaterally restricted carpal range of motion on kinematic gait analysis of the dog. Vet Comp Orthop Traumatol 2003;16:158-163. 12. Bishop KL, Pal AK, Schmidt D. Whole body mechanics of stealthy walking in cats. PLoS One 3(11):e3808. doi: 10.1371/journal.pone.0003808 13. Watson C, Rochat M, Payton M. Effect of weight bearing on the joint angles of the fore- and hindlimb of the dog. Vet Comp Orthop Traumatol 2003;16:250-254. 14. Li D, Bennett D, Gibbs C, et al. Radial carpal bone fractures in 15 dogs. J Small Anim Pract 2000;41:74-79. 15. Tomlin JL, Pead MJ, Langley-Hobbs SJ, et al. Radial carpal bone fracture in dogs. JAAHA 2001;37:173-178. 16. Guilliard MJ, Mayo AK. Subluxation/luxation of the second carpal bone in two racing greyhounds and a Staffordshire bull terrier. J Small Anim Pract 2001;42:356-359. 17. Miller A, Carmichael S, Anderson TJ, et al. Luxation of the radial carpal bone in four dogs. J Small Anim Pract 1990;31:148154. 18. Guilliard MJ. Accessory carpal bone displacement in two dogs. J Small Anim Pract 2001;42:603-606. 19. Lenehan TM, Tarvin GB. Carpal accessorioulnar joint fusion in a dog. JAVMA 1989;194(11):1598-1600. 20. Benson JA, Boudrieau RJ. Severe carpal and tarsal shearing injuries treated with an immediate arthrodesis in seven dogs. JAAHA 2002;38:370-380.

21. Ralphs SC, Beale BS, Whitney WO, Liska W. Idiopathic erosive polyarthritis in six dogs (description of the disease and treatment with bilateral pancarpal arthrodesis). Vet Comp Orthop Traumatol 2000;13:191-196. 22. Marcellin-Little DJ, Sellon RK, Kyles AE, et al. Chronic localized osteomyelitis caused by atypical infection with Blastomyces dermatitidis in a dog. JAVMA 1996;209(11):1877-1879. 23. Pedersen NC, Pool RR, O’Brien T. Feline chronic progressive polyarthritis. Am J Vet Res 1980;41:522-535. 24. Cook JL, Payne JT. Surgical treatment of osteoarthritis. Vet Clin North Am Small Anim Pract 1997;27(4):931-943. 25. Berg J, Gliatto JM, Wallace MK. Giant cell tumor of the accessory carpal bone in a dog. JAVMA 1990;197(7):883-885. 26. Keller WG, Chamber JN. Antebrachial metacarpal arthrodesis for fusion of deranged carpal joints in two dogs. JAVMA 1989; 195(10):1382-1384. 27. Innes JF, McKee WM, Mitchell RAS, et al. Surgical reconstruction of ectrodactyly deformity on four dogs. Vet Comp Orthop Traumatol 2001;14:201-209. 28. Gemmill TJ, Clarke SP, Carmichael S. Carpal agenesis in a domestic short haired cat. Vet Comp Orthop Traumatol 2004;17:163166. 29. Johnson KA. A radiographic study of the effects of autologous cancellous bone grafts on bone healing after carpal arthrodesis in the dog. Vet Radiol 1981;22(4):177-183. 30. Martinez SA, Walker T. Bone grafts. Vet Clin North Am Small Anim Pract 1999;29(5):1207-1219. 31. Montgomery RD, Long IR Jr, Milton JL, et al. Comparison of aerobic culturette, synovial membrane biopsy, and blood culture medium in detection of canine bacterial arthritis. Vet Surg 1989;18(4):300-303. 32. Willer RL, Johnson KA, Turner TM, et al. Partial carpal arthrodesis for third degree carpal sprains: a review of 45 carpi. Vet Surg 1990;19(5):334-340. 33. Denny HR, Barr ARS. Partial carpal and pancarpal arthrodesis in the dog: a review of 50 cases. J Small Anim Pract 1991;32:329334. 34. Johnson KA. Partial carpal arthrodesis. 10th ESVOT Congress 2000:43-44. 35. Parker RB, Brown SG, Wind AP. Pancarpal arthrodesis in the dog: a review of forty-ﬁve cases. Vet Surg 1981;10(1):25-43. 36. Viguier E, Znaty D, Medelci M, et al. In vitro comparison between a DCP and external ﬁxators for pancarpal arthrodesis in the dog. Equine Vet J 2001;(Suppl 33):32-35. 37. Haburjak JJ, Lenehan TM, Davidson CD, et al. Treatment of carpometacarpal and middle carpal joint hyperextension injuries with partial carpal arthrodesis using a cross pin technique: 21 cases. Vet Comp Orthop Traumatol 2003;16:105-111. 38. Wininger FA, Kapatkin AS, Radin A, et al. Failure mode and bending moment of canine pancarpal arthrodesis constructs stabilized with two different implant systems. Vet Surg 2007;36:724728.

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39. Theoret MC, Moens NM. The use of veterinary cuttable plates for cuttable plates for carpal and tarsal arthrodesis in small dogs and cats. Can Vet J 2007;48:165-168. 40. Smith MM, Spagnola J. T-plate for middle carpal and carpometacarpal arthrodesis in a dog. JAVMA 1991;199(2):230-232. 41. Husle D. Use of plate/rod technique for carpal arthrodesis. 10th ESVOT Congress 2000:41-42. 42. Michal U, Fluckiger M, Schmokel H. Healing of dorsal pancarpal arthrodesis in the dog. J Small Anim Pract 2003;44:109-112. 43. Guerrero TG, Montavon PM. Medial plating for carpal panarthrodesis. Vet Surg 2005;34:153-158. 44. Chambers JN, Bjorling DE. Palmar surface plating for arthrodesis of the canine carpus. JAAHA 1982;18:875-882. 45. Toombs JP. Transarticular application of external skeletal ﬁxation. Vet Clin North Am Small Anim Pract 1992;22(1):181-194. 46. Okrasinski EB, Pardo AD, Graehler RA. Biomechanical evalu-

ation of acrylic external skeletal fixation in dogs and cats. JAVMA 1991;199:1590-1593. 47. Lotsikas PJ, Radasch RM. A clinical evaluation of pancarpal arthrodesis in 9 dogs using circular external skeletal fixation. Vet Surg 2006;35:480-485. 48. Worth AJ, Bruce WJ. Long-term assessment of pancarpal arthrodesis performed on working dogs in New Zealand. NZ Vet J 2008;56:78-84. 49. Whitelock RG, Dyce J, Houlton JEF. Metacarpal fractures associated with pancarpal arthrodesis in dogs. Vet Surg 1999;28:2530. 50. Seguin B, Harari J, Wood RD, et al. Bone fracture and sequestration as complications of external skeletal fixation. J Small Anim Pract 1997;38:81-84. 51. Kostlin R. Pancarpal arthrodesis—dorsal plate. 10th ESVOT Congress 2000:39-40.

3 CE CREDITS

CE TEST 2 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. Which statement regarding arthrodesis is true? a. Arthrodesis is the immobilization of a joint by a combination of osteophytosis, enthesiophytosis, intraarticular fibrosis, periarticular fibrosis, capsular adhesion, and musculotendinous contracture. b. Arthrodesis will not restore pain-free joint function. c. Arthrodesis is defined as the surgical stabilization and removal of joint motion by bony fusion of joint surfaces. d. Arthrodesis is recommended in select joints, such as the hip, elbow, or stifle. 2. Which anatomic structures are important in stabilizing the carpus? a. palmar fibrocartilage, short radial ligament, and extensor carpi radialis tendon b. short ulnar ligament, short radial ligament, flexor retinaculum, palmar fibrocartilage, and accessory ligaments c. short ulnar ligament, short radial ligament, flexor retinaculum, and abductor pollicis longus tendon d. palmar fibrocartilage, superficial digital flexor tendon, and short radial ligament 3. Most flexion occurs at which joint space? a. ABC b. MC c. CM d. the same amount of flexion occurs at ABC and MC 4. Which statement regarding the general principles of arthrodesis is true?

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a. The final angle of fusion does not need to be considered. b. Articular cartilage must be removed from all bones of the joint(s) to be fused. c. Bone grafts can be inserted into the joints being fused but do not enhance bone formation or shorten healing time. d. Rigid stabilization of the joints to be fused is unnecessary. 5. _________ is/are not a good indication for arthrodesis. a. Ligamentous injuries, carpal fractures, and luxations b. Congenital malformations leading to luxations c. Chronic osteoarthritis or immunemediated disease leading to instability d. High radial nerve injury 6. Which statement regarding radiographic findings with carpal instabilities is false? a. Instability at the CM joint may lead to the proximal carpal bones overriding the distal row. b. With an instability of the MC joint, a gap between the palmar process of the ulnar carpal bone and the base of the fifth metacarpal is seen and the caudal aspect of the accessory carpal bone appears tipped proximally. c. With chronic ABC injuries, radiographs show wearing of the palmar edge of distal radius due to subluxation of the proximal carpal bones. d. Decreased angle of extension is seen at the ABC joint on a stressed lateral view.

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7. When deciding between partial or pancarpal arthrodesis, which is the most important factor? a. which joint(s) is/are affected b. the increased cost (to the owner) of pancarpal arthrodesis c. the length of time in external coaptation d. the difference in weight bearing on the contralateral limb 8. The most common method of pancarpal arthrodesis is a. medial plating. b. ESF. c. dorsal plating. d. cross-pinning. 9. Which statement regarding the use of circular ESF for carpal arthrodesis is true? a. It is used only with open or infected wounds. b. It does not require any additional equipment compared with traditional linear ESF. c. It can be used with success in dogs without open wounds to avoid bandage or plate complications. d. Producing the proper angle of fusion is very easy with this technique. 10. Which of the following is the most serious complication of arthrodesis? a. nonunion b. diaphyseal fracture of the third metacarpal c. implant loosening or breaking d. osteomyelitis

Case Report Particularly intriguing cases

Ovarian Teratoma in a Mediterranean Tortoise

❯❯ Jaime Martorell, DVM, PhD ❯❯ Sara Soto, DVM ❯❯ Sara Barrera, DVM ❯❯ Antonio Ramis, DVM, PhD, DECVP Universitat Autònoma de Barcelona Barcelona, Spain

Abstract: A 61-year-old female Mediterranean tortoise (Testudo hermannii) presented after 1 week of tetraparesis. Coelomic ultrasonography revealed free ﬂuid and an ovarian mass with multiple follicles. Blood analysis suggested renal failure. After initial medical treatment for kidney disease, the tortoise seemed to improve clinically, but the animal died 2 months later. Necropsy and histopathology revealed an ovarian teratoma. To our knowledge, this is the ﬁrst reported case of a teratoma in tortoise gonadal tissue.

Presentation

FIGURE 1

Radiographs revealing small foreign bodies (fb) in the digestive tract, loss of normal coelomic structure definition, and lung compression (lc). FIGURE 2

Ultrasonographic image of free liquid (fl) in coelomic cavity and an ovarian teratoma (T) with several round echoic structures resembling ovarian follicles in different maturation stages.

A 61-year-old female Mediterranean tortoise (Testudo hermannii) presented after 1 week of tetraparesis. The owner reported that the animal had not laid eggs that year but had shown nesting behavior. The tortoise was housed outdoors, where it was in contact with concrete, soil, trees, and grass. It hibernated in winter, when temperatures were above 41°F to 46°F (5°C to 8°C); in spring, temperatures were above 73°F (23°C), and in summer, above 86°F (30°C). The tortoise had free access to water and was fed mainly romaine and iceberg lettuce and some other vegetables and fruits, mostly oranges and apples. No supplements were added to the diet. On physical examination, the animal weighed 4.4 lb (2 kg) and had sunken eyes. On neurologic examination, the tortoise was alert but had tetraparesis that manifested as slow limb retraction when the digits were squeezed and inability to stand up and walk, even though its muscular condition was apparently good. Fecal analyses (direct observation and Gram staining) were unremarkable. Survey radiographs revealed two small foreign bodies of mineral density, presumably within the digestive tract; loss of normal coelomic structure deﬁnition; and lung compression (FIGURE 1). Ultrasonography showed free liquid in the coelomic cavity and several rounded hyperechoic and hypoechoic structures that resembled ovarian follicles in different stages of maturation (FIGURE 2). The kidneys appeared small (1.17 × 0.8 cm) but had a normal

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193

Case Report: Ovarian Teratoma in a Mediterranean Tortoise TABLE 1

Hematologic and Blood Chemistry Results

Parameter Packed cell volume (%)

Results at Presentation

Results at 1-Month Follow-Up

Reference Range1,2 28–34

White blood cells (×10 /μL)

25.2

10.6

0.7–4.2

Lymphocytes (×103/μL)

5.71

0.95

0.31–2.9

Monocytes (×103/μL)

1.37

0.85

0–0.8

Heterophils (×103/μL)

18.1

8.79

0.37–1.85

Calcium (mg/dL)

28.1

13.7

7.6–14.7

Phosphorus (mg/dL)

9.17

3.94

2.6–8.8

Uric acid (mg/dL)

62.84

3.97

0.1–2

Creatine kinase (IU/L)

370.5

245.2

26–215

Total protein (g/dL)

4.14

2.34

3.3–6.5a

Albumin (g/dL)

1.09

0.48

1.68–3.01a

α1 Globulin (g/dL)

0.16

0.86

0.09–0.44a

α2 Globulin (g/dL)

0.96

0.21

0.74–1.53a

β Globulin (g/dL)

1.76

0.69

0.28–1.36a

γ Globulin (g/dL)

0.16

0.09

0.13–0.19a

cells/μL). The results of aerobic culture of the fluid were negative. Hematology and blood chemistry results indicated renal disease with an infection/ chronic inflammatory reaction1,2 (TABLE 1). The differential diagnosis included coelomitis (of various etiologies, including infection and yolk) and renal disease. Endoscopy and biopsy were recommended, but the owner refused. Medical treatment was initiated with the administration of enrofloxacin1–3 (Baytril, Bayer Animal Health; 5 mg/kg PO q48h for 2 weeks), allopurinol 3 (Zyloric, Glaxo Wellcome; 10 mg/kg PO q24h), and vitamin B complex3 with L-carnitine (Hepadif suspension, Reig Jofre, Barcelona, Spain; 25 mg/ kg PO q24h), and a homemade soft vegetarian diet of mostly green leaves was recommended.

Outcome

Although the tortoise seemed to improve with Reference range from the Clinical Biochemistry Service of the Veterinary School of the Universitat Autònoma de Barcelona, Barcelona, Spain. medical treatment, it died 2 months after presentation. The animal was submitted for a echoic appearance (FIGURE 3). No other abnor- postmortem examination. malities were observed. On gross examination, the coelomic aponeuA coelomic ﬂuid sample analysis revealed rosis appeared markedly thickened. All the an exudate effusion (total protein: 3.48 mg/dL, coelomic organs had major adhesions to a 20,000 red blood cells/μL, 1300 white blood spherical, intracoelomic, cystic mass 12 cm in FIGURE 3

Ultrasonographic images of coelomic organs.

Normal liver and gallbladder (between calipers).

194

Right kidney (between calipers). The kidney has a normal echoic appearance but is small.

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Case Report: Ovarian Teratoma in a Mediterranean Tortoise diameter. The mass was filled with an undetermined amount of brownish fluid and covered with a well-vascularized, fibrous capsule. Its wall was irregularly thickened, and numerous verrucous, yellow-white masses protruded into the lumen (FIGURE 4). Some of these masses were covered with a shiny, black, rigid layer reminiscent of scales. The cystic mass and the liver demonstrated some variably sized yolklike structures (between 0.15 and 2.5 cm in diameter) on their dorsal surfaces. Gross identification of any ovarian or adrenal tissue was not possible. Histologically, there were some rounded basophilic structures (300 to 500 μm in diameter), lined by few concentric granulosa cell layers, that were associated with the capsule of the cystic mass and corresponded to ovarian follicles. There were also small, rounded eosinophilic structures compatible with yolk that occasionally appeared to elicit a granulomatous reaction with associated cholesterol crystals. The cystic mass was composed of a dense, collagenous matrix occasionally lined by keratinized, stratified squamous epithelium (FIGURE 5) that corresponded to the black scales described above. Multiple cystic cavities were covered by either simple cubical to cylindrical, pseudostratified, ciliated epithelium (FIGURE 6) with goblet cells or keratinized, stratified squamous epithelium; in some cases, epithelial cells were grouped in acinar-like structures. Although there were no overtly differentiated tissues, the observed epithelial structures could have corresponded to tissues from different germ layers (respiratory tract, skin). The cavities were filled with either granular, mucinous, basophilic, occasionally calcified material or eosinophilic aggregates of keratin. Multiple islands of cartilaginous tissue (FIGURE 7), hemorrhagic areas, and scattered foci of mixed inflammation (with heterophils, lymphocytes, and macrophages) were seen. Due to its location and its composition by mature tissues from the different embryonic layers (ectoderm, mesoderm, and endoderm), the cystic mass was diagnosed as a benign teratoma. Among the remaining organs, only the kidneys had significant lesions with tubulointerstitial fibrosis and multifocal granulomatous nephritis, in which some macrophages contained intracytoplasmic fungal hyphae.

FIGURE 4

The ovarian teratoma with ﬂuid-ﬁlled vesicles.

Discussion Teratomas are parthenogenic tumors that develop from a single germ cell4 and differentiate into tissue from at least two embryonic layers: ectoderm, mesoderm, or endoderm.5 They may be benign or malignant. Malignant teratomas are undifferentiated, with both mature and embryonal elements.5,6 Teratomas have been described in mammals, birds, and amphibians. FIGURE 5

Histologic section of the teratoma showing keratinized stratified squamous epithelium (kse) and vascularized fibrous stroma (vfs).

FIGURE 6

Histologic section of the teratoma showing pseudostratified ciliated epithelium (pce) and vascularized fibrous stroma (vfs).

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195

Case Report: Ovarian Teratoma in a Mediterranean Tortoise FIGURE 7

Histologic section of the teratoma showing simple cylindric epithelium (sce) and an island of cartilaginous tissue (ct).

In reptiles, this neoplasm has previously been diagnosed in lizards7–10 and snakes.11 The only two cases previously described in chelonians were malignant and benign ovarian teratomas described in red-eared sliders (Trachemys scripta elegans).12,13 The carapace and plastron can limit the extent of ultrasonographic examination of the coelomic organs in small chelonians; however, reproductive masses can be identiﬁed using ultrasonography.7,14 In the present case, endos-

copy would have been essential to conﬁrm an ovarian mass because the presence of many round masses of mixed echogenicity resembled follicles in different maturation stages. In this case, despite the response observed to the initial treatment, the chronic coelomitis associated with the large ovarian teratoma and the renal disease were likely the causes of death. All of these alterations caused a chronic wasting that could have contributed to the development of tetraparesis. Fungal lesions were only found in the kidneys. Mycotic pneumonia is more prevalent than mycotic kidney disease in chelonians, and renal fungal infections are generally related to systemic mycoses.15 The presence of fungal forms in the kidney could have been caused by an ascending infection from the cloaca or bladder or by hematogenous spread from an initial focus that was previously resolved. A similar case of a renal fungal infection caused by Geotrichum candidum was reported in a giant tortoise (Geochelone nigra).16 In the case described here, a microbiologic culture was not performed and fungi were only observed microscopically. To our knowledge, this is the ﬁrst reported case of ovarian teratoma in a Mediterranean tortoise (T. hermannii), and this condition should be considered in the differential diagnosis of intracoelomic neoplasms and gonadal masses in tortoises.

References 1. Dietthelm G. Reptiles. In: Carpenter JW, ed. Exotic Pet Formulary. 3rd ed. St. Louis: Elsevier Saunders; 2005:55-134. 2. López-Olvera JR, Montané J, Marco I, et al. Effect of venipuncture site on hematologic and serum biochemical parameters in marginated tortoise (Testudo marginata). J Wildl Dis 2003;39(4):830-836. 3. Bonner BB. Chelonian therapeutics. Vet Clin North Am Exotic Anim Pract 2000;3(1):257-332. 4. Schlafer DH, Miller RB. Female genital system. In: Maxie M, ed. Jubb, Kennedy and Palmer’s Pathology of Domestic Animals. 5th ed. Edinburgh, Scotland: Saunders Elsevier; 2007:429-564. 5. MacLachlan NJ, Kennedy PC. Tumors of the genital systems. In: Meuten DJ, ed. Tumors in Domestic Animals. 4th ed. Ames: Iowa State University Press; 2002:547-574. 6. Rosai J, Ackerman LV. Female reproductive system. In: Rosai J, ed. Rosai and Ackerman’s Surgical Pathology. 9th ed. St. Louis: Elsevier; 2004:1483-1762. 7. Anderson NL, Williams J, Sagartz JE, Barnewall R. Ovarian teratoma in a green iguana (Iguana iguana). J Zoo Wildl Med 1996;27:90-95. 8. Garner MM, Hernandez-Divers SM, Raymond JT. Reptile neoplasia: a retrospective study of case submissions to a specialty diagnostic service. Vet Clin North Am Exotic Anim Pract 2004;7(3):653-671.

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9. Mauldin GN, Done LB. Oncology. In: Mader DR, ed. Reptile Medicine and Surgery. St. Louis: Saunders Elsevier; 2006:299-322. 10. Tocidlowski ME, Merrill CL, Loomis MR, Wright JF. Teratoma in desert grassland whiptail lizards (Cnemidophorus uniparens). J Zoo Wildl Med 2001;32(2):257-259. 11. Hertha DW, Giles HD, Frye FL. Ovarian teratoma in a garter snake (Thammophis sirtalis). J Herpet Med Surg 2002;10(3-4):22-23. 12. Hidalgo-Vila J, Martínez-Silvestre A, Díaz-Paniagua C. Benign ovarian teratoma in a red-eared slider turtle (Trachemys scripta elegans). Vet Rec 2006;159(4):122-123. 13. Newman SJ, Brown CJ, Patnaik AK. Malignant ovarian teratoma in a red-eared slider (Trachemys scripta elegans). J Vet Diagn Invest 2003;15(1):77-81. 14. Mehler SJ, Rosentein DS, Patterson JS. Imaging diagnosis: follicular torsion in a green iguana (Iguana iguana) with involvement of the left adrenal gland. Vet Radiol Ultrasound 2002;43(4):343-345. 15. Paré JA, Sigler L, Rosenthal KL, Mader DR. Microbiology: fungal and bacterial diseases of reptiles. In: Mader DR, ed. Reptile Medicine and Surgery. St. Louis: Saunders Elsevier; 2006:217-238. 16. Ruiz JM, Arteaga E, Martinez J, et al. Cutaneous and renal geotrichosis in a giant torotise (Geochelone elephantophus). Sabouraudia 1980;18(1):51-59.

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

Product Forum Geriatric Canine Supplement

Dermatology Products

Polychews is an oral supplement speciﬁcally designed to meet the unique needs of aging and geriatric dogs. It is formulated to comprehensively meet the needs of older dogs experiencing joint stiffness or inﬂammation. Polychews de contains bioavailable ingredients that provide support for multiple immune system and energy pathways. Arthrodynamic Technologies, Inc. 888-549-4503 | arthrodynamic.com

DermaPet has released MalAcetic Ultra, a new product designed to manage conditions responsive to acetic and boric acids, ketoconazole, and hydrocortisone. Designed for topical treatment of fungal and bacterial infections, MalAcetic Ultra is available in three different formulations; an ear cleanser, a shampoo, and a leave-in conditioner. DermaPet | 800-755-4738 | dermapet.com

Pet Recovery Service The Lost Pet Alert service, offered as a supplement to the American Kennel Club's Companion Animal Recovery (AKC CAR), offers pet owners an extra layer of protection for their lost companions. The AKC CAR program currently consists of a microchip recovery system. The addition of Lost Pet Alert allows owners to create an online proﬁle for their pet that, if the pet goes missing, is sent to participating pet owners, animal shelters, veterinary clinics, animal control ofﬁces, and petfriendly businesses within a 50-mile radius. Lost Pet Alert has a one-time fee. American Kennel Club Companion Animal Recovery 800-252-7894 | akccar.org

Testing Equipment IDEXX has increased the capabilities of its SNAPshot Dx Analyzer to include a wider range of testing. The SNAPshot Dx Analyzer can now automatically time the assay and interpret the results of SNAP FIV/FeLV Combo and SNAP cPL qualitative tests. The Dx Analyzer can also add the results to the patient’s record. IDEXX plans to add other members of the SNAP family of tests to the SNAPshot Dx later this spring. IDEXX Laboratories | 800-283-8386 | idexx.com

Topical Tissue Adhesive

Joint Supplements

GLUture topical tissue adhesive is an octyl/butyl cyanoacrylate blend designed to create a strong and ﬂexible bond on wounds. Designed by Abbott Animal Health, GLUture is purple when applied, offering higher visibility, but becomes clear as it dries. It comes in a multi-use package with 10 applicators. Abbott Animal Health | 888-299-7416 | abbottanimalhealth.com

Teva Animal Health has introduced two new products for animal joint health. DVM Feline Joint Gel helps maintain healthy bone, connective tissue, and joint structure and function in aging cats. It is ﬂavored with poultry and tuna for easy administration. PhyCox-JS Small Bites are mini soft chews designed with a joint support formula to help reduce inﬂammation and discomfort in small dogs. Teva Animal Health | 800-759-3664 | tevaanimalhealth.com

Unit Dose Bins Manufactured from highimpact, durable polystyrene, EPS’s Unit Dose Bins ﬁt 36-inch-wide shelves and can be ﬁtted to EPS Gravity Flow Rails. The rails, constructed from sturdy zinc-plated steel, allow the bins to hang at a 20˚ angle so products can be seen but won’t fall out. The bins are useful for dispensing liquid and solid unit dose medications. EPS, Inc. | 800-523-8966 | medidose.com

Handheld Radiography System The NOMAD Pro Veterinary is a handheld radiography system designed speciﬁcally for veterinary dental use. It features a color LCD screen and weighs only 5.5 lb. The NOMAD Pro incorporates modern internal shielding to block radiation leakage and a backscatter shield to protect the operator. Battery life gives hundreds of diagnostic-quality radiographs per charge, and operation is driven by an icon-based system. Aribex, Inc. | 866-340-5522 | aribex.com

The product information presented here is provided by the manufacturers and does not reﬂect endorsement by Compendium.

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197

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

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Product

Page

Abbott Animal Health

SevoFlo

200, inside back cover

ACVIM

ACVIM Forum Montréal

Back cover

Bayer Animal Health

Baytril

158, 159

Boehringer Ingelheim Vetmedica

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Dechra Veterinary Products

Vetoryl

155, 156

Hill’s Pet Nutrition

PetFitness VetSync

Inside front cover (Canada only)

Nestlé Purina PetCare

Case in Brief: FortiFlora

169

Northgate Veterinary Supply

Glass cage doors and rod gates

198

Novartis Animal Health

Sentinel

177, 178–179

Veterinary Association Management

Veterinary Conferences

Inside front cover (US only)

Vetstreet

Pet Portal Service

163

WhereTechsConnect.com

Job Marketplace

198

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Abbott_USE.qxp:1

SevoFlo®

2/18/09

9:31 AM

Page 2

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

SEVO-152 January 2007

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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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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.

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

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 200 for Product Information Summary

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