Compendium | July 2009 by davidpsu

VOLUME 31 NUMBER 7 JULY 2009

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L Limited Fluid Volume F Resuscitation

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I Intracranial M Meningioma in Dogs and Cats

CONTI N U I NG EDUCATION FOR VETERI NARIANS ®

Clinical Snapshot Reading Room NEW SERIES

Regulation of Pet Foods in the United States by David A. Dzanis

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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! *

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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, DACVIM, DACVECC University of Missouri-Columbia

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

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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, DVM, PhD, DACVIM Gulf Coast Veterinary Specialists Houston, Texas

Nephrology Catherine E. Langston, DVM, DACVIM 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.

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 300 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

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

July 2009 Vol 31(7)

Features 309

330

FREE

Limited Fluid Volume Resuscitation ❯❯ Tara N. Hammond and Jennifer L. Holm Volume replacement therapy is crucial to the treatment of hypovolemic shock, but traditional therapy with crystalloid ﬂuids may not be ideal for these patients.

CE C

Case Report: A Beagle with Head Trauma PAGE 311

Intracranial Meningioma in Dogs and Cats: A Comparative Review

CompendiumVet.com | Peer Reviewed | Listed in MEDLINE

324 Focus on Nutrition

NEW SERIES

Regulation of Pet Foods in th the U United it d States

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❯❯ Kara Sessums and Christopher Mariani Learn how the clinical signs and treatment of this common primary brain tumor differ between dogs and cats.

❯❯ David A. Dzanis Dr. Dzanis, an expert consultant for the pet food and related industries, shares his knowledge of how pet food and supplements are regulated at the federal and state levels. Dr. Dzanis is a former chairman of the Association of American Feed Control Ofﬁcials. He has also worked for the US Food and Drug Administration, where he had scientiﬁc oversight of all matters relating to pet food labeling and nutrition.

Immunohistochemical staining of an anaplastic canine meningioma PAGE 331

Departments 302 CompendiumVet.com 304 Clinical Snapshot Dermatosis in a Persian ❯❯ Julie Hunt 306 Reading Room Vault Guide to Veterinary and Animal Careers 307 The Editor’s Desk: Food for Thought ❯❯ Robin Henry 322 Research Recap Selected abstract from Veterinary Therapeutics

Clinical Snapshot PAGE 304

329 Abstract Thoughts ❯❯ Joseph Harari

340 Product Forum

On the Cover

341 Market Showcase

Dr. David A. Dzanis, of Dzanis Consulting & Collaborations, researches pet food regulations in the United States.

341 Classiﬁed Advertising 343 Index to Advertisers

*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®

301

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2009 Vol 31(7)

CE ARTICLES

❯❯ Renal Secondary Hyperparathyroidism 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. ORY FORM DIET HIST _______ ________________ ________________ ________ Date: ________ ________________ ________________ Case Number: n _______ Owner Informatio ________________ ________________ ________ Name: ________ ________________ ________ ________________ Email address: ________________ ________________ __________ Phone (home): ________________ __________ ________________ Phone (cell): ________________ call:_____________ Best time to

Yes P No the day? P 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 _______ P Yes P No ________________ ____ describe:_________ If yes, please ________________ ________________ ____ ________ ________ ________________ ________________ ____ ________________ ________________ ________________ ____ ________ ________ ________________ ________________ to each other’s ________________ _ have access one pet, do they ________________ than Reason for Visit more ________ describe: If you have ____ If yes, please ________________ ____ ________________ ___________ P Yes P No ___ food? food ________________ ________________ ____________ ________________ ____ ________ ________________ ________ ________ ________ ________ ________________ ________________ ________________ ____________ ________________ ________________ _ ________ ________ ___ hics ____ ____________ ________ ________ _ ________________ ________ ________ Household Demograp ? ________________ ________ _________ ho ________ ____ our household ________ ________ _____________ are in your hey? are they? ________ ________ _____ ________________ How many adults , and how old ________________ ________________ ________ ____ aree in your household ________________ _____________ ________________ ________________ How many children et’s food? ________ ________________ ____ ____ ________________ ________ store your pet’s ______ _____________ ________ _________ How do you ________________ ________ ________________ _____ ________ ________________ ________ __ ________ ________ ____ _ ____ ________ ________ ________ ________ ________ ____ ________ ________ ________________ ________ ________________ ______________ ________ ________ ________________ ________ ________ ______ ________ ____ ______ ____ ________ ________ ____________ ________ ________ __________ ________________ ________ ________________ _____________ ________ ________ ________ ________ __ _____ ________ ___ ____ _____ ________ P Both _________ ________ ________ ________ ________________ P Outdoors ________ __ ________ ____________ P Indoors __ ________________ ____ list species ________ r pet housed? ____ ________________ ________________ Where is your No If so, please P Yes PBehav DIE________________ other other pets? ior ________________ T HISTO Do you have indoors inddoors or outdoors. ____ What is RY FOR _______ ________ cify if they live your speci ________ and specify ________ pet’s ________ M ________ attitud ________ _ _ ____ ____ e toward Activity ________ P Gre________ _________________ food? ed ________ ________ ________________ ________ P Indifferenc ________ your pet? Table foods ________ __ ____ ________ Has your ________ How active is e P Avo ________ _____________ P Averageor scaps; ________ pet’s attitud ________ ________________ ________ idance ________ e P Very active _____ home-prepar ________ ___ e toward ____ ________ _____ __________ ________ ________ ________ food changP Hyperactiv ed foods moves __________ ________ ________ _______________ __________ ________________ __________ ed? so, active P Hardly _____ ________________ ____ ________ _____ __________ P NotIf very _____ describe: ________ ________ __________ __________ __________ ________ ________ ______________ _____ walked? ________ pet __________ _____ day a your __________ _____is_____ __________ P Once __________ _____________ _____ ________ How often _______ __________ __________ _______ P 1-2 times/day ________ _____________ __________ __________ 3 times/day __________ At least __________ _____ __________ P_____ __________ __________ _____ __ __________ P No _______________ ent __________ __ P Never ____________ __________ Managgement eeding Managem P Yes _____ Feeding Fee __________ __________ P Seldom If ________ __________ you have ________ __________ ____ _____ __ __________ P No_______________ _______ ds your pet? other pets, feeds feed ________ access to__a yard? ________ ________ P Yes _____ Who typically Wh you have is this pet ________ __________ Dietary Do_____ __________ ________ P Dom ________ __________ ____ ant domin ________ inant ________ ________ __ __ your pet? supplements _____________ ________ P No to exercise __________ or P Sub ________ food used ________ _________________ P; Yes it difﬁcult __________ Issubmi Has ________ missive ssive to ________ your ________ _______ to ________ pet recent _________ __________ __________ ________ increased? P No give pills be them? ly lost or ____________ P Yes_____ ________________ Can exercise _____ __________ gained weight __ ________ ____ _____ _____ training? in fed? d et pet p ________ ________ __________ _____ P No __________ ________ ? If Has ________ When is your __________ P Yes your pet participate _____ so, please ________ ________ n? __________ __________ __________ __ ________ ________ competitio __________ _________ describe: ________ ________ ___________ _____ __ __________ __________ your pet participated in ________ ________ ________________ _____ __________ ________ Has_____ ________ _____ __________ ____ __________ __________ ________ ___ ________ _____ _____ _____ ________ ________ ___ __________ __________ __ __________ __________ __ ________________ ________________ ________________ ________ _____ __________ __________ __________ __________ __________ ________ __________ _________________ __________ __ __ __________ __________ ________________ __________ Have there __________ __________ __________ List anythi __________ been any ng else __ __ __________ __________ given by recent chang __________ __________ __________ mouth (e.g., _______ es in activity __________ __ __________ medications level? _____ __________ __________ __________ __________ ): _____ __________ __________ __________ __________ __________ __________ __________ __________ __________ __________ __________ __________ __ __ __________ __________ Have you __________ __________ __________ __________ __________ observed __________ __ __ __________ __________ any of the __________ Nausea/saliv __________ __________ __________ following: __ ation __ __________ __________ Difﬁculty __________ __________ __________ chewing __ __________ __________ P Yes Dysphagia Is your __________ __________ P No pet’s curren __ __________ P Yes t diet a chang Vomiting __________ P No P Yes e from its P No __ typical diet? P Yes If so, please Diarrhea P No describe P Yes the chang __________ Constipation P No e and why __________ the diet P Yes Have there __________ __________ was chang P No been any ed. __________ __________ changes P Yes __________ __________ __________ in urinati P No on? __________ __________ Diet __ P Yes __________ __________ __________ P No __________ __________ For each __ of __________ __________ __________ cable) and the following catego __________ __________ __ ries, __________ __________ __________ often each amounts of all foods your list the brand names __________ food is __________ __ fed (e.g., pet eats (if appli- Are you __________ __________ Commercial daily, as twice a open to day). __________ well as __ foods making how a chang __________ __________ P Yes e in your P No __ __________ pet’s diet? What are __________ __________ your pet’s __________ __________ food prefere __________ __________ __________ __________ nces?______ __________ __________ __________ __ __________ __________ __________ __________ __________ __________ ______ __________ __________ __________ __________ __ __________ __________ __________ __________ __________ __________ __________ __________ __ __________ __________ __ What foods __________ __________ Commercial __________ __________ does your __________ __ treats; dental __________ __ pet refuse __________ __________ __________ __________ hygiene ? _____ __________ products __ __________ __________ __ __________ __________ __________ __________ __________ __________ __________ __________ __________ __________ __________ __________ __________ __________ __________ __________ __________ __ __________ __________ __ __________ Are there __________ __________ __________ __________ foods to __________ __ __________ __________ __ which your __________ If so, which __________ __________ pet is allergi __________ foods? __ __________ c? P __________ __ __________ Yes P __________ __________ __________ __________ No __________ __________ __ _____ __________ __________ __________ __________ __________ __________ _ __ __________ __________ __________ __________ __________ __ __________ __________ __________ __ __________ __

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

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

❯❯ Jenefer R. Stillion and Michelle G. Ritt Parathyroid gland hyperplasia and subsequent hyperparathyroidism can occur secondary to chronic renal failure in dogs, resulting in significant alterations in calcium metabolism. Renal secondary hyperparathyroidism is a complex, multifactorial syndrome that involves changes in circulating levels of calcium, parathyroid hormone (PTH), phosphorus, and 1,25-dihydroxycholecalciferol (calcitriol). An increased PTH level can have many deleterious effects. Dietary phosphorus restriction, intestinal phosphate binders, and calcitriol supplementation may slow the progression of renal disease and decrease PTH concentrations in animals with secondary hyperparathyroidism.

❯❯ Feline Nonregenerative Anemia ❯❯ Carrie White and Nyssa Reine Anemia in cats is not a diagnosis but rather a sign of an underlying disease. The diagnostic work-up for an anemic patient is often extensive. If nonregenerative anemia is identiﬁed, a number of tests may be required to determine its cause, including a close examination of the patient’s blood and bone marrow. Although there are standard supportive measures for anemic cats, speciﬁc therapies can be implemented for certain etiologies of nonregenerative anemia. Part one of this article addresses the pathophysiology and etiologies of nonregenerative anemia in cats; part two provides an overview of diagnosis and treatment.

WEB-EXCLUSIVE VIDEOS

❯❯ Laparoscopic and LaparoscopicAssisted Cryptorchidectomy Videos The June 2009 Surgical Views column, “Laparoscopic and Laparoscopic-Assisted Cryptorchidectomy in Dogs and Cats,” by Dr. Philipp Mayhew, discusses the advantages and disadvantages of these techniques. This article is available online, along with three videos that demonstrate some of the techniques discussed.

❯❯ Cryptorchidectomy Video 1

VIDEO 1. Manipulation of the normal testicle

in a unilaterally cryptorchid dog. By pushing the normal testicle in a cranial direction, it is possible to see whether the normal testicle is located on the right or the left side.

❯❯ Cryptorchidectomy Video 2

VIDEO 2. Use of a vessel-sealing device to

seal and section the gubernaculum, spermatic cord, and vascular pedicle of an abdominally cryptorchid testicle.

❯❯ Cryptorchidectomy Video 3

VIDEO 3. Removal of a cryptorchid testicle

through a subumbilical port. This allows enlargement of the port through the linea alba rather than the muscular body wall where the instrument ports are located.

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Compendium

Canadian News

Coming Events August 8–13 World Association for the Advancement of Veterinary Parasitology: 22nd International Conference Calgary, Alberta This conference will discuss current issues in parasitology. Web waavp.org September 9 Calgary Academy of Veterinary Medicine: Ophthalmology Clara Christie Theatre, Health Sciences University of Calgary, Alberta This seminar will offer 1.5 hours of scientiﬁc CE and will be presented by Dr. Cheryl Cullen. Phone 403-863-7160 E-mail info@cavm.ab.ca Web cavm.ab.ca/ce_calendar.html September 15 Toronto Academy of Veterinary Medicine: Update on Clinical Gastroenterology Dave and 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 October 13 Toronto Academy of Veterinary Medicine: Early Resuscitation and Stabilization of the Emergency Patient Dave and Buster’s Toronto, Ontario This seminar will focus on practical emergency management by using case examples. It will offer 5.5 CE credits. Phone 800-670-1702 Web tavm.org October 18 Calgary Academy of Veterinary Medicine: Hematology Clara Christie Theatre, Health Sciences University of Calgary, Alberta This seminar will offer 6 hours of scientiﬁc CE and be presented by Dr. Marjorie Brooks. Phone 403-863-7160 E-mail info@cavm.ab.ca Web cavm.ab.ca/ce_calendar.html November 13–14 Lifelearn Inc. Continuing Education: Small Animal Laser Surgery Ontario Veterinary College University of Guelph, Ontario This seminar will offer 14 hours of CE credit. It is designed to provide practitioners with an introduction to the uses of CO2 lasers in veterinary surgery. Phone 800-375-7994 Web www.lifelearn.com

Inﬂammatory Bowel Disease Research Under Way A

team of 22 researchers, led by Dr. Herman Barkema, of the University of Calgary, is exploring the underlying causes of inﬂammatory bowel disease (IBD), a debilitating gastrointestinal disease. The research is being funded by a grant from the Alberta Heritage Foundation for Medical Research. The participating scientists are from a variety of institutions, including the University of Calgary, University of Alberta, University of Toronto, and University of Manitoba. The researchers will be studying a variety of factors, including genes, microbes, and pollution, to determine whether these factors contribute to

the development of IBD. Because the disease affects many different species, including humans, the team will also be looking into connections between human and animal medicine. The University of Calgary faculty of veterinary medicine is committed to strengthening the connections between human and animal medicine, a concept known as One Health. “We are looking at humans, because if we understand how this disease happens in one species, we can apply it to others,” says Barkema. “IBD exists in many species, including cattle, sheep, dogs, and some wildlife, and it has devastating health, social, and ﬁnancial impacts.”

OVC Opens Centre for Public Health and Zoonoses

he Ontario Veterinary College (OVC) at the University of Guelph has officially opened the new Centre for Public Health and Zoonoses. The center will bring together scientists in a variety of fields to address new and reemerging zoonotic diseases such as the H1N1 flu virus, bird flu, E. coli O157:H7, and West Nile virus. “Up to 75% of emerging diseases that pose a threat to human health originate in animal populations, whether it’s avian flu or new strains of antibioticresistant ‘superbugs,’” said the centre’s director, Jan Sargeant, an OVC professor. “We have an important role to play in developing knowledge and expertise in this area and integrating them in the public health system.” Globalization has increased the threat and severity of zoonotic disease outbreaks and, according to Sargeant, veterinarians are uniquely equipped to investigate the public health effects of these outbreaks and propose solutions to them. The cen-

tre will study a variety of ﬁelds, including diseases in food animals, companion animals, and wildlife.

SPREAD YOUR GOOD NEWS Have any interesting news to share? Send it in! We would like to provide more recognition of veterinarians doing great things in their professional or personal lives. If you have news about yourself or a colleague or about some other newsworthy topic that would be of interest to others in the profession, send it (along with a picture if you have one) to: Canadian News c/o Veterinary Learning Systems 780 Township Line Road Yardley, PA 19067, USA E-MAIL editor@CompendiumVet.com FAX 800-556-3288 WEB CompendiumVet.com

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

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VETORYL Capsules (trilostane) ®

10 mg, 30 mg, and 60 mg strengths

Clinical Snapshot

Adrenocortical suppressant for oral use in dogs only

Particularly intriguing or difﬁcult cases 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 indicatedfor 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. Angiotensinconverting 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. 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.

(trilostane) Distributed by: Dechra Veterinary Products 7015 College Boulevard, Suite 525 Overland Park, KS 66211 www.VETORYL.com 866-933-2472 VETORYL is a trademark of Dechra Ltd. © 2009, Dechra Ltd. NADA 141-291, Approved by FDA

Case Presentation #1 ❯❯ Julie Hunt, DVM Hermitage Veterinary Hospital Hermitage, PA

A 3-year-old spayed Persian cat presented with a chronic, nonpruritic, slowly progressive dermatosis limited to the face. Lesions consisted of black material adherent to the hair, regional crusting, and mild erythema. These lesions were present in the periocular area and facial folds and on the dorsal muzzle and chin. The cat also had chronic otitis externa. The cat was indoor only and up-to-date on all routine medical care. It had contact with one other housecat, which was unaffected. In an effort to manage the dermatosis, the cat had been treated with antibiotics (amoxicillin–clavulanic acid, 20 mg/kg for 10 days; then cefovecin

304

sodium, 8 mg/kg SC, one dose), injectable corticosteroids (methylprednisolone acetate, 5.5 mg/kg SC, one dose), a 60-day novel protein diet, selamectin (once monthly, three doses), and miconazole–chlorhexidine pledgets (Malaseb, DVM Pharmaceuticals; daily use on the face). Despite these treatments, the dermatosis continued to progress. 1. What additional diagnostic tests would be useful for this case? 2. What dermatopathy does this cat have? 3. What treatment is currently recommended for this dermatopathy? SEE PAGE 308 FOR ANSWERS AND EXPLANATIONS.

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

BIG

VETORYL (trilostane) is now available in 10 mg capsules! ®

NEWS

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

Results like these. Effective treatment for Cushing’s syndrome is now FDA approved for dogs of any size.

Prior to

VETORY L treatmen t

Access to the most powerful weapon in the fight against canine Cushing’s syndrome just got easier. VETORYL capsules are the only FDA veterinary-approved treatment for pituitary-dependent and adrenal-dependent hyperadrenocorticism.

ment g 3 months off treat ng win Folloowi YL RY RYL TOR h VETO wiith

Now available in 10 mg, 30 mg, and 60 mg capsules! 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 veterinary distributor to order VETORYL Capsules s today!

Followin ng

9 month hs

of treatm en

t with VE

Photogra phs courte sy of Carlos M elian, DVM , PhD

(trilostane) 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. VTYL0709-01-48047-CPD

See Page 304 for Product Information Summary

TORYL

Reading Room*

T This guide should provide a good start for both young adults making a career choice and people considering a career change. Title: Vault Guide to Veterinary and Animal Careers Authors: Liz Stewart and the staff of Vault Publisher: Vault.com Year: 2008 Pages: 141 ISBN: 978-1-58131-548-6

TO LEARN MORE For further information about this book or to order a copy, visit vault.com.

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HE WEB-BASED VAULT CAREER GUIDES have won high praise from a number of prominent magazines and newspapers, including The New York Times, The Washington Post, Money, Fortune, and Forbes. Designed to answer some basic questions (e.g., “What are the career opportunities in working with animals?” “Is this the right job for you?”), this guide covers everything “from soup to nuts”—what jobs are available, how to get each one, and what each will be like. Although the emphasis is firmly The book concludes with a chapon the practical, the book begins by ter on “alternative job opportunities” providing a brief background about related to animals, such as educaanimals in society. It then moves on tion, sales, advocacy, law, and media. to industry trends, from zoos to eco- A useful appendix lists professional tourism and from scientific research organizations, schools, and helpful to farming. Web sites. The core of the book features This guide should provide a good sections on the wide range of jobs start for both young adults making a available to those who wish to make career choice and people considering a career of working with animals, a career change. The approach takes including veterinary medicine (doc- a lighter tone—for example, listing tors, technicians, and assistants), “uppers” and “downers” for each job— breeding, farming/ranching, animal but never diverges from the pragmatic. control, zoo and wildlife management, The language is clear and intelligent research, service industries, and cor- and does not “dumb down” the subporate and government positions. Follow ing this is a SHARE YOUR COMMENTS chapter on employers for Have a question or comment about each of these categories. this book review? Let us know: The discussion then shifts E-MAIL editor@CompendiumVet.com to how to get the job in question—education and FAX 800-556-3288 train ing, breaking into WEB CompendiumVet.com the field at various levels (including starting a business), constructing a resume, ject matter. And as befits the puband interviewing. The next chap- lisher’s strong Web connections, the ter takes the reader on the job, book recognizes the role today’s addressing lifestyle and financial information technology plays in the issues and providing “career snap- job market. For those who love anishots” comprising interviews of mals, this book should help to deterpeople who hold the job in ques- mine whether their passion might tion. Interviewees offer details on translate into practical work. duties, hours, and pros and cons, *Written by Patricia L. Van Horn, a freelance along with nuggets of advice. writer in Long Branch, New Jersey.

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

The Editor’s Desk ❯❯ Robin Henry, Senior Editor

Food for Thought

his morning, as I was preparing my daily series (Feline Focus, Surgical Views, Focus on dose of coffee, my cat Sam gave me one Nutrition, and Applied Dermatology), a growing of those looks that only a cat can give bank of online resources at CECenter.com you. Outside, a thunderstorm was making the and VetLearn.com, and a monthly e-newsletter, sky resemble the beginning of The Wizard of Oz, Compendium Extra. It takes a talented, committed and Sam—no fool—was on his way to the base- team of people to make it all come together every ment just in case the house decided to take off. month, and I’m fortunate enough to be part of one. At the top of the basement steps, he turned and looked at me, dressed for work and getting ready Compendium readers also have to face the weather, and his big, golden, Maine sharp eyes and wits and aren’t shy Coon eyes said it all: “So where are you going?” Sam—like his domestic shorthair “brother,” about e-mailing with questions when Angel—has no concept of work, of course. Among the clutter on my office bulletin board, I have something doesn’t seem to add up. one panel of a Get Fuzzy cartoon, in which Rob (the resident human) is yelling at Satchel Pooch More importantly, I know that what we do and Bucky Katt, “Don’t all thank me at once for every month matters. In my previous jobs, on the going out and supporting you two!” Satchel’s reply human side of medical publishing, communicais, “Now…where do you go every day?” Bucky’s is tions went one way: the publications I worked more pragmatic: “Bring back food.” I’ve labeled the on went out into the world and disappeared, like characters in the strip as “me,” “Sam,” and “Angel,” radio signals into space. Not so with Compendium. in that order. That’s how it is with cats and work: Many Compendium readers have a relationship blissful ignorance. On days when the weather with the journal that goes back years—or even makes my morning alarm seem even earlier than it decades—and many have told me so is, I greatly envy my cats. with pride. At this year’s ACVIM con_And yet...the past 2½ years as ference, several people stopped by the senior editor of Compendium Veterinary Learning Systems booth and have probably been the most commented on how much they apprerewarding so far in my 13 ciate the journal. Meanwhile, here in years of working in the the office, we were fielding e-mails health care publishing from readers eager to read upcoming industry. They’ve been online articles. i nterest i ng— some Compendium readers also have times in a “may you sharp eyes and wits and aren’t shy live in interesting times” about e-mailing with questions when kind of way—and chal- something doesn’t seem to add up. lenging. The journal has These e-mails always make me wince, undergone a complete rede- but only because I’m a perfectionist by sign, and we’ve launched four new nature and hate to realize I missed

Sam

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

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The Editor’s Desk something. The questions themselves are welcome. They prove that not only is the journal being read, but it’s being read carefully, by people who find it worthy of comment and correction. So it’s worth getting up and enduring the pity of my cat on a blustery morning. Sam and Angel will never understand why I let that infernal alarm disturb them 5 days a week, but on the other hand, they can’t know the rewards of being involved with a community of people with such an ongoing drive to learn and share knowledge. Reading the articles and communicating with the authors and readers of Compendium make me think hard every day, and I enjoy that. So I’d like

to say thank you to everyone who contributes their time to this journal, whether by writing for it, reviewing it, or reading it. It is a privilege to work with all of you. And as long as I remember to bring back food, Sam and Angel would agree.

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

Clinical Snapshot Answers and Explanations Case Presentation #1 2. The diagnosis in this case was pre-

SEE PAGE 304 FOR CASE PRESENTATION.

1. Helpful diagnostic tests may include

skin cytology, skin scraping, skin biopsy, and dermatophyte test medium (DTM) culture. Skin cytology of the facial folds showed epithelial cells, occasional inﬂammatory cells, a few cocci, and heavy infection with Malassezia organisms. The skin scraping samples were negative for parasites. DTM culture results were negative, and the skin lesions did not ﬂuoresce under a Wood’s lamp. The owner declined a skin biopsy.

SHARE YOUR PICTUREPERFECT CASES IN CLINICAL SNAPSHOT

308

sumptive idiopathic facial dermatitis of Persian cats, also known as dirty face syndrome. It is reported most commonly in young Persian and Himalayan cats. It is thought to be inherited. This progressive disease is characterized by dark, greasy, exudative material that adheres to the distal portions of hairs in the facial folds (perioral and nasolabial) and, less commonly, nonintertriginous locations.1,2 The muzzle, periorbital areas, and chin are most commonly affected. Although the condition is initially nonpruritic, pruritus is reported with chronicity, along with erythema.2 There is a strong correlation with bilateral ceruminous otitis externa.2 Secondary conditions may be present, such as pyoderma and this cat’s Malassezia infection. Secondary conditions can be managed; however, the underlying syndrome responds poorly to most treatments.2

3. Treatments for idiopathic facial

dermatitis include topical antiseborrheic products, management of infections, and oral modified cyclosporine (5 to 7 mg/kg/day initially).3 As in this case, Malassezia infection in cats typically occurs secondary to other dermatoses, but it may also exist as a primary infection in cats with acne or comedones.4 Malassezia infection can be treated topically with antiseborrheic products or systemically with azole antifungals.4

References 1. Paradis M, Scott DW. Hereditary primary seborrhea oleosa in Persian cats. Feline Pract 1990;18(1):17-20. 2. Bond R, Curtis CF, Ferguson EA, et al. An idiopathic facial dermatitis of Persian cats. Vet Dermatol 2000; 11:35-41. 3. Fontaine J, Heimann M. Idiopathic facial dermatitis of the Persian cat: three cases controlled with cyclosporine. Vet Dermatol 2004;15:64. 4. Ordeix L, Galeotti, F, Scarampella F, et al. Malassezia spp overgrowth in allergic cats. Vet Dermatol 2007;18(5): 316-323.

Challenge your colleagues with a particularly intriguing or difficult case in Clinical Snapshot. Submit your photo(s) along with a brief case description, at least one test question, and detailed answers to each question posed. Each published submission entitles you to an honorarium of $100. For more details, call 800-426-9119, extension 52412, or e-mail editor@CompendiumVet.com

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

3 CE CREDITS

CE Article 1

Limited Fluid Volume Resuscitation ❯❯ Tara N. Hammond, DVM, DACVECC Tufts Veterinary Emergency Treatment & Specialties Walpole, Massachusetts

❯❯ Jennifer L. Holm, DVM, DACVECC Angell Animal Medical Center Boston, Massachusetts

At a Glance Traditional Versus Limited Fluid Volume Resuscitation Page 310

Fluid Distribution and Dynamics

Abstract: Volume replacement therapy is crucial to the treatment of hypovolemic shock. In patients with certain conditions, limiting the volume of fluid administered has many potential therapeutic benefits and technical advantages. Hypertonic saline and colloids have characteristics that allow effective treatment of hypovolemic shock using relatively smaller volumes than would be required for isotonic crystalloids alone. This article describes the theory and clinical application of limited fluid volume resuscitation in veterinary medicine.

emorrhage is a common cause of hypovolemic shock in veterinary patients and can occur with trauma, coagulopathy, or rupture of a parenchymal mass. In general, affected animals were previously healthy and are acutely hypovolemic due to hemorrhage in the chest or abdomen or along a long bone fracture. The goal of rapid volume replacement in shock is to restore perfusion as quickly as possible by replacing intravascular losses and controlling further bleeding, thus limiting tissue injury that can result in organ dysfunction and

death. However, the decision of whether fluid replacement or hemorrhage control takes priority and which fluid type to use is controversial. Research has shown improved hemodynamic parameters and outcomes with the use of limited fluid volume resuscitation (LFVR) in patients with hypovolemic shock.1–10 However, few clinical veterinary trials have been performed. This article reviews fluid distribution in the body, describes the use of LFVR in hypovolemic shock, and summarizes selected experimental and clinical studies of LFVR.

Acceptable End Points of Resuscitation15,16

TABLE 1

Parameter

Value

Mentation

Alert

Mucous membranes

Pink

Capillary reﬁll time

<2 sec

Temperature

100°F–102.5°F

Heart rate

Cats: 180–220 bpm Small-breed dogs: 100–160 bpm Large-breed dogs: 60–100 bpm

Respiratory rate

20–40 breaths/min

Systolic blood pressure

>100 mm Hg*

Mean blood pressure

>80–100 mm Hg*

Central venous pressure

5–10 cm H2O

Lactate

<2.5 mmol/L

Urine output

At least 1–2 mL/kg/hr

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Case Report: A Beagle with Head Trauma Page 311

Fluids Used in Limited Fluid Volume Resuscitation Page 313

Research in Limited Fluid Volume Resuscitation Page 318

*Active, noncompressible hemorrhage may be the exception, and achieving a mean arterial pressure (MAP) of 70 mm Hg or a systolic arterial pressure (SAP) of 90 mm Hg with improvement of clinical signs during limited ﬂuid volume resuscitation (LFVR) is acceptable until hemorrhage is deﬁnitively controlled.

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Traditional Versus Limited Fluid Volume Resuscitation

QuickNotes Limited ﬂuid volume resuscitation is particularly beneﬁcial for animals with hemoperitoneum, pulmonary contusions, traumatic brain injury, and other sources of ongoing hemorrhage.

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The aim of any fluid therapy regimen for treating hypovolemic shock is resolution of shock, not simply administration of a specific volume of fluid. In addition, volume dosages for any type of fluid must be tailored to the individual patient, and recommended dosages are guidelines only. Treating hypovolemic shock is a dynamic process that requires frequent evaluation of the patient. The end points of optimal resuscitation include alleviation of peripheral vasoconstriction and decreased perfusion, as demonstrated by normalization of vital signs and other objective parameters (TABLE 1). Traditionally, isotonic crystalloids have been used at dosages based on estimated blood volume (90 mL/kg/hr in dogs, 40 to 60 mL/ kg/hr in cats) to replace intravascular losses.11 Although they are essential in the treatment of dehydration, isotonic crystalloids can prolong the time needed to restore effective circulating volume, redistribute rapidly into the interstitial space, and contribute to hypothermia. Because <20% of an administered isotonic crystalloid remains in the intravascular space after 1 hour, large volumes of isotonic crystalloids may be required to maintain an effective circulating volume and may result in excessive interstitial edema.12 Alternatives to isotonic crystalloids include colloids and hypertonic saline (HS). Colloids and HS are used at much smaller volumes than isotonic crystalloids, enabling faster administration and more rapid repletion of the intravascular space. Colloids are also retained in the intravascular space for longer periods of time than crystalloids and are therefore more effective at maintaining adequate circulating volume and reducing the risk of interstitial edema. Research has shown that HS may have additional benefits, such as restoration of cellular function following traumatic brain injury and immune system modulation. LFVR, also called small-volume resuscitation, differs from hypotensive resuscitation or delayed fluid resuscitation in that it is aimed at achieving normalization of clinical end points. With hypotensive or delayed fluid resuscitation, the patient is permitted to remain hypotensive or fluids are withheld, respectively, until bleeding is definitively controlled. During hypotensive resuscitation, the patient is resuscitated

to a mean arterial blood pressure (MAP) of no greater than 60 mm Hg, which just maintains perfusion to vital organs while minimizing the risk of dislodging vascular clots.1,13,14 During delayed fluid resuscitation, no fluids are given until defi nitive control of hemorrhage is achieved. Once bleeding is controlled in either situation, aggressive fluid resuscitation is initiated. The goal of LFVR is to use the smallest volume of fluid possible to restore the intravascular compartment and resolve shock while minimizing fluid extravasation into the brain or lungs and the risk of disrupting an incipient blood clot.11 LFVR should be considered in cases with hemoperitoneum, traumatic pulmonary contusions, traumatic brain injury, and other forms of active hemorrhage (BOX 1). In patients with active, noncompressible hemorrhage, achieving an MAP of 70 mm Hg or a systolic arterial pressure (SAP) of 90 mm Hg with improvement of clinical signs during LFVR is acceptable until hemorrhage is definitively controlled.15,16 Once acceptable clinical parameters have been achieved, the dosage and type of fluid can be adjusted to meet the current and anticipated needs of the patient.

Fluid Distribution and Dynamics Total body water accounts for approximately 60% to 70% of body weight.17 Of this water, 66% is located in the intracellular space (including red blood cell mass) and 33% in the extracellular space. The extracellular space is subdivided into intravascular (25%) and interstitial (75%) compartments, which are separated by endothelial cells and a basement membrane.11,17 The membrane is permeable to water but not to most solutes, creating differences in osmotic pressure between the compartments. Osmotic pressure is determined by the number of nonpermeable particles in solution.11 A solution that has more, fewer, or an equal number of osmotically active particles per unit of volume or weight compared with intracellular ﬂuid is said to be hyperosmolar, hyposmolar, or isosmolar, respectively. Water moves across the basement membrane from areas of low solute concentration to areas of high solute concentration via osmosis. Sodium is the most abundant cation in the extracellular ﬂuid and accounts for most of the osmotically active particles in this space. The

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Limited Fluid Volume Resuscitation CE BOX 1

Case Report: A Beagle with Head Trauma A previously healthy 19-kg [41.8-lb], 3.5-year-old castrated beagle presented to an emergency facility after being hit by a car. The physical findings were consistent with hypovolemic shock (TABLE A): lateral recumbency, pale mucous membranes, hypothermia, tachycardia, weak femoral pulses, tachypnea, and a moderate increase in respiratory effort. Other pertinent physical findings included harsh lung sounds bilaterally and signs consistent with head trauma (mild anisocoria, scleral hemorrhage, epistaxis). Due to signs of head trauma and suspicion of pulmonary contusions, a limited fluid volume resuscitation protocol was implemented. A fluid bolus of 80 mL (4.2 mL/kg) of 7.3% sodium chlo-

TABLE A

ride was administered simultaneously with 200 mL (10.5 mL/ kg) of 6% hetastarch IV. Other supportive measures employed included an external passive warming source and supplemental oxygen. Hemodynamic parameters normalized after the bolus (TABLE A), and the epistaxis and anisocoria resolved. Supportive care was continued in addition to administration of lactated Ringer’s solution, 25 mL/hr (1.3 mL/kg/hr) IV; 6% hetastarch, 4 mL/hr (0.2 mL/kg/hr) IV; and hydromorphone, 0.95 mg (0.05 mg/kg) IV q6h. Thoracic radiography revealed right-sided pulmonary contusions and a small amount of right-sided pleural effusion likely due to hemorrhage (FIGURES A AND B). The dog recovered fully and was discharged.

Physical Findings on Admission and After Resuscitation

Physical Findings

Temperature (°F)

Heart Rate (bpm)

Respiratory Rate (breaths/ min)

Mucous Membrane Color

Femoral Pulse Quality

Systolic Blood Pressure (mm Hg)

Lactate (mMol/L)

Initial

97.5

180

Pale

Weak

TLTD

8.6

After resuscitation

99.4

120

Pink

Strong

120

1.4

TLTD = too low to determine

Thoracic radiographs of the dog in this case. FIGURE A

FIGURE B

Dorsoventral view. Note the right-sided pulmonary contusions (arrows) and a small amount of right-sided pleural effusion (arrowheads) likely due to hemorrhage.

Lateral view.

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volume of extracellular fluid is determined by total body sodium content, whereas the osmolality and sodium concentration of extracellular fluid are determined by water balance. Regulation of sodium and water balance by the kidneys18 maintains the volume and osmolarity of body fluids within a narrow normal range. In response to the renin–angiotensin–aldosterone system, brain atrial natriuretic hormones, and the posterior pituitary–vasopressin–renal axis, the kidneys maintain extracellular fluid sodium levels and tonicity and contribute to the maintenance of blood pressure.19 Normally, fluid movement between the intravascular and interstitial compartments depends on membrane pore size and differences between FIGURE 1

osmotic, hydrostatic, and colloid osmotic pressure (COP), according to Starling’s law of capillary hemodynamics (BOX 2 AND FIGURE 1).17 The major source of intravascular COP is albumin. As the COP increases, ﬂuid movement out of the intravascular space decreases and the amount of plasma ﬂuid retained increases, causing the intravascular hydrostatic pressure to rise. Fluid movement out of the intravascular space occurs in three situations: (1) when the intravascular hydrostatic pressure is greater than the COP, (2) when capillary permeability increases, or (3) when intravascular COP falls BOX 2

Glossary of Fluid Balance Terms11,17,34

Starling’s law of capillary hemodynamics states that net fluid movement (v) at the level of the capillary is a result of the balance of forces favoring fluid movement out of the vessel (hydrostatic pressure of the vasculature [Pc] and the COP of the interstitium [ ∏ if]) and forces favoring fluid movement into the vasculature (hydrostatic pressure of the interstitium [Pif] and the COP of the vasculature [∏c]). Fluid dynamics are also a function of the permeability of the endothelium, which in the Starling equation is the reflection coefficient (ó). The last factor that determines net fluid movement is net lymph flow (Q l).

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Colloid: A large molecule that cannot penetrate the capillary membrane and is therefore retained in the intravascular space, creating colloid osmotic pressure. Colloid osmotic pressure (COP): Osmotic pressure created at the capillary membrane by colloids and plasma proteins retained within the intravascular or interstitial space. Hydrostatic pressure: The natural tendency of water to move out of a fluid compartment, determined by cardiac output and systemic vascular resistance at the capillary membrane and driven by arterial blood pressure against a vessel wall. Osmolality: The concentration of a solution in terms of osmoles of solute per kilogram of solution, independent of any membrane. Osmolarity: The concentration of a solution in terms of osmoles of solute per liter of solution, independent of any membrane. Osmotic pressure: Pressure required on one side of a membrane to oppose the movement of water molecules across the membrane from the other side. Starling’s law of capillary hemodynamics: States that fluid flux at the capillary level is controlled by a balance between hydrostatic and osmotic pressure gradients between capillaries and the interstitial space. Tonicity: A measure of effective osmolarity or effective osmolality. A property of a solution in reference to a particular membrane, equal to the sum of the concentrations of the solutes that have the capacity to exert an osmotic force across the membrane.

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Limited Fluid Volume Resuscitation CE below the interstitial COP12 (BOX 3). Any watercontaining fluid (e.g., crystalloids) given intravenously can move out of the vasculature and into the interstitium via any of these mechanisms, and the process may be exaggerated after injury. In many conditions (e.g., acute pancreatitis, trauma, bite or burn wounds), fluid is lost from the intravascular space via more than one of these mechanisms. Vasculitis causes increased systemic vascular permeability, and plasma proteins and fluid are sequestered into the interstitial space, resulting in interstitial edema.19 Interstitial edema can also occur as a result of lymphatic obstruction or leakage or when interstitial fluid accumulation exceeds lymphatic drainage.12

Fluids Used in Limited Fluid Volume Resuscitation TABLE 2 summarizes the advantages and disad-

vantages of the various types of ﬂuids used in resuscitation of hemorrhaging patients, including isotonic crystalloids. Dosing recommendations for the various types of ﬂuids used in LFVR are summarized in TABLE 3.

Hypertonic Crystalloids The most commonly used hypertonic crystalloid is HS containing 7.2% to 7.5% sodium chloride (depending on the manufacturer), although solutions containing 3% to 23.4% sodium chloride are available. HS is best used in previously healthy animals with acute hypovolemia. The high sodium content of HS rapidly pulls ﬂuid from the extravascular space via the osmotic gradient to expand intravascular volume, resulting in rapid resolution of shock at low infusion volumes. When HS is used alone, this effect typically lasts less than 30 minutes. However, when HS is used in combination with colloids, the effect on volume expansion (and therefore cardiac output) is sustained for 2 to 3 hours. HS and colloids can be mixed for simultaneous administration, and the rate of administration should not exceed 1 mL/kg/min. Using HS is advantageous because it more rapidly restores intravascular circulating volume at smaller infusion volumes compared with isotonic crystalloids alone. Shock resolves faster with less personnel time, and the period of hypoperfusion is minimized. It is an ideal solution for resus-

BOX 3

Conditions Causing Fluid Movement From the Intravascular Space Into the Interstitium12 Conditions causing intravascular hydrostatic pressure greater than COP Intravascular ﬂuid overload Hypertension Heart failure Anaphylaxis Conditions causing increased capillary permeability Systemic inﬂammation Vasculitis Sepsis Immune-mediated disease Excessive vasodilation Trauma Conditions causing intravascular COP less than interstitial COP Hypoalbuminemia Previous hemorrhage Protein-losing enteropathies Glomerulopathies End-stage hepatic failure COP = colloid osmotic pressure

citation in transit (e.g., ambulance, battlefield, search and rescue), when there are volume restrictions, or in large animals with acute hypovolemia. HS should never be used as the only fluid therapy because it dehydrates the interstitium. It should be followed by isotonic crystalloids with or without colloids. HS has many properties that other fluids do not. It has beneficial effects on the heart, including increased inotropy, chronotropy, coronary blood flow, and venous return. Increases in renal, splanch nic, and coronary blood flow have been attributed to a decrease in peripheral vascular resistance and redistribution of cardiac output.4 HS has also been shown to decrease leukocyte adhesion and migration, which may help to blunt the inflammatory response and activation of the coagulation cascade.20–22 It has been shown to reduce albumin leakage, neutrophil counts in bronchoalveolar lavage fluid, and histopathologic injury compared with resuscitation using lactated Ringer’s solution.23 HS use in hemor-

QuickNotes Crystalloids cannot maintain intravascular volume or tissue perfusion for extended periods of time and should not be the sole source of intravascular ﬂuid therapy in patients with refractory hypovolemic shock.

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TABLE 2

Advantages and Disadvantages of Different Fluid Types in Resuscitation11,12,34,39,42,50

Fluid Type

Advantages

Disadvantages

Low cost Necessary in dehydration Widely available Long storage life

Large volumes needed Longer time to resuscitate Require more technical staff (e.g., placement of multiple, large-gauge IV catheters) Risk of hypothermia Risk of interstitial edema Risk of hemodilution Risk of rebleeding

Hypertonic saline (7.2%–7.5%)

Low cost Small volumes needed for rapid resuscitation Minimizes risks of interstitial edema Beneﬁcial neurologic effects; decreases intracranial pressure Immunomodulatory effects Beneﬁcial cardiac effects

Short acting when used alone Transient hypernatremia Hypotension, bronchoconstriction, or arrhythmias with rapid administration Risk of volume overload Possible phlebitis Hyperosmolar

Synthetic colloids (6% hetastarch,

Smaller volumes needed for rapid resuscitation compared with crystalloids Minimizes risks of interstitial edema Longer duration of effect Increases COP Less hemodilution

Higher cost Risk of volume overload Exacerbation of coagulopathies Risk of allergic reactions Edema with vasculitis Interference with crossmatching

Increases COP Increases oxygen delivery Eliminates need to crossmatch 2-year shelf life

Higher cost Risk of volume overload Possible risk of anaphylaxis with multiple uses Inability to measure certain blood values after use

Isotonic crystalloids (lactated Ringer’s solution, 0.9% sodium chloride, Normosol-R,a Plasmalyte Ab)

10% pentastarch, 6% dextran 70)

Hemoglobin-based oxygen carrier (Oxyglobinc)

COP = colloid osmotic pressure. a Abbott Laboratories. b Baxter. c Biopure.

rhagic shock also prevents immunosuppression after injury by decreasing plasma levels of interleukin-4 and certain prostaglandins and by limiting neutrophil activation, bacterial translocation, and pulmonary lesions.24–26

Hemoperitoneum Hemoperitoneum is one of the most common emergencies in veterinary medicine. Cases may be due to trauma or may be spontaneous. Most spontaneous cases are caused by rupture of a neoplasm. Most veterinarians agree that the main treatment goals are to reestablish or maintain effective circulating volume, maintain oxygen-carrying capacity, and arrest

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ongoing hemorrhage.27 However, which goal takes precedence and which fluid resuscitation protocol to use are controversial. LFVR to achieve specific end points (i.e., SAP ≤90 mm Hg, MAP ≤70 mm Hg, normalization of clinical signs) should be considered in these cases. Until hemorrhage is arrested, the use of small boluses of HS and colloids help to resolve shock and perfuse vital organs. At MAPs of 60 to 70 mm Hg, cerebral and renal blood flow are preserved.27 LFVR also helps minimize the risk of clot disruption caused by sudden increases in intravascular hydrostatic pressure, thereby reducing the risk of rebleeding during resuscitation.

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Limited Fluid Volume Resuscitation CE TABLE 3

Shock Doses for Acute Volume Resuscitation11,12,36,39,42,50

Fluid

Isotonic crystalloids (lactated Ringer’s solution, 0.9% sodium chloride, Normosol-R, Plasmalyte A)

Hypertonic saline (7.2%–7.5%)

Hydroxyethyl starches (6% hetastarch, 10% pentastarch)

IV Dosage

Dogs: 90 mL/kg (give 20–30 mL/kg IV over 10–15 min and reassess) Cats: 45–60 mL/kg (give 10–15 mL/kg IV over 10–15 min and reassess) Give in 10- to 15-mL/kg increments over 10–15 min with frequent reassessment Dogs and cats: 3–8 mL/kg Give no faster than 1 mL/kg/min Dogs: 10–20 mL/kg Cats: 10–15 mL/kg Give in 5-mL/kg increments over 10–15 min with frequent reassessment

6% Dextran 70

Dogs: 10–20 mL/kg Cats: 10–15 mL/kg Give in 5-mL/kg increments over 10–15 min with frequent reassessment

Oxyglobin

Dogs: 10–30 mL/kg Not labeled for use in cats Do not exceed 10 mL/kg/hr

Traumatic Brain Injury HS is particularly useful in treating patients with traumatic brain injury, cerebral edema, and increased intracranial pressure (ICP). It has been shown to decrease ICP and increase survival following head injury.3,28,29 HS is effective at reducing brain volume because it does not cross the blood–brain barrier and mobilizes interstitial fluid from the brain into the intravascular space. Mannitol works in a similar fashion with a longer duration of action, but it also induces an osmotic diuresis, leading to further volume loss.30–32 It is critical to maintain a cerebral perfusion pressure (CPP) above 70 mm Hg in dogs and cats. Given that CPP = MAP – ICP and that normal ICP in dogs and cats is approximately 5 to 10 mm Hg, MAP must be maintained above 80 mm Hg.33 Hypotension is one of the most important extracranial contributors to secondary neurologic damage with traumatic brain injury. Fluid therapy should never be withheld in patients with traumatic brain injury, as dehydration only minimally decreases ICP and fluid restriction can result in hypovolemia, compromising CPP. In these patients, the goal is to balance fluid therapy and treat shock (thereby ensuring adequate oxygen delivery) without exacerbating cerebral edema or bleeding. With head injury, adenosine triphosphate depletion leads to retention of sodium in the

intracellular space, which results in intracellular accumulation of water and calcium and extracellular liberation of excitatory amino acids (e.g., glutamine). HS helps to increase extracellular sodium concentrations and restore gradients so that calcium is returned to the extracellular space and glutamate to the intracellular space, limiting secondary injury and neuronal death.20,33 It also works to minimize vasospasm, encourage local vasodilation, and limit endothelial cell swelling and permeability by promoting microcirculatory blood ﬂow and improving local oxygen delivery.

QuickNotes Hypertonic saline is contraindicated in patients with dehydration, cardiac failure, renal failure, or hyperosmolar conditions (e.g., diabetic ketoacidosis).

Pulmonary Contusions The management of pulmonary contusions is controversial, with clinical studies yielding inconsistent results. However, pulmonary contusions, which have been reported in up to 50% of animals with thoracic trauma, are another potential indication for LFVR.16 With pulmonary contusions, the alveolar capillary membranes sustain damage and the alveoli flood with blood, impairing ventilation. HS can be beneficial in these patients, as administration of large amounts of isotonic crystalloids during resuscitation may exacerbate pulmonary parenchymal compromise and further impair ventilation, especially during the first 24 hours after resuscitation. It is recommended that fluid therapy be given to restore

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and maintain cardiac output and tissue perfusion while avoiding excessive interstitial edema. Although controversial, HS and colloids should be considered the treatment of choice (with judicious use of isotonic crystalloids) until further research suggests otherwise.34

Adverse Effects and Contraindications

QuickNotes The concentrations and molecule sizes of synthetic colloids determine the initial amount and duration of intravascular volume expansion, respectively.

TABLE 4

Adverse effects of HS administration can include transient hypernatremia, occasional premature ventricular contractions, bradyarrhythmias, temporary hypotension, and bronchoconstriction.35 However, with appropriate patient selection and administration (no faster than 1 mL/ kg/min), these effects are rare. In addition to rapid increases in cardiac output and blood pressure, the sodium load of HS may elevate the risk of congestive heart failure in some patients. Also, HS may promote blood loss at the site of vascular injury due to breakdown of a blood clot (i.e., rebleeding). Clinically signiﬁcant rebleeding has not been observed in studies when current dosing recommendations were followed.28,36–38 In fact, the MAP and SAP in experimental swine that experienced rebleeding were found to be 64 ±2 mm Hg and 94 ±3 mm Hg, respectively, during treatment, arguably supporting the use of LFVR so that the SAP does not exceed 90 mm Hg.36 Contraindications to HS use include dehydration, preexisting hypernatremia, cardiac failure, hyperosmolar conditions (e.g., diabetic ketoacidosis), renal failure, and intravascular volume overload.39 It is essential to monitor electrolyte levels in patients receiving HS. As with any sudden increase in sodium, there is a potential for neurologic signs due to cellular dehydration and acute neuronal shrinkage. HS

can cause an increase in sodium and chloride concentrations and a decrease in potassium and bicarbonate levels, but these are of minimal clinical importance unless the animal has preexisting electrolyte abnormalities. HS can also increase serum osmolarity by 20 to 30 mOsm in hydrated patients, but this generally normalizes within a few hours.15

Synthetic Colloids Colloids exert a prolonged effect on intravascular volume compared with isotonic crystalloids, achieving better tissue perfusion and restoration of blood pressure at lower infusion volumes. In addition to LFVR for acute hypovolemia, colloids may be indicated in animals with hypoalbuminemia, decreased COP, or increased capillary permeability. Colloids can be biologic (e.g., blood, albumin, plasma) or synthetic (hetastarch, pentastarch, tetrastarch, dextran, gelatin, hemoglobin-based oxygen carrier [HBOC]). Biologic colloids are indicated for a variety of conditions but are rarely used as sole ﬂuid support in shock. Synthetic colloids have molecular weights of 69,000 Da (the weight of albumin) or greater. In healthy patients, they cannot pass through the basement membrane of the intravascular space; therefore, they contribute to increases in the intravascular COP. Practitioners should be familiar with the concentrations and molecule sizes of synthetic colloids, which determine the initial amount and duration of intravascular volume expansion, respectively. The properties of synthetic colloids are summarized in TABLE 4.34,40,41 The use of a bolus of colloids at 5 mL/kg to achieve an SAP of no greater than 80 to 90 mm

Properties of Synthetic Colloids34,40,41 Molecular Weight Range (Da)

Weight Average Molecular Weight (Da)a

Number Average Molecular Weight (Da)b

Colloid Osmotic Pressure (mm Hg)c

6% Hetastarch

10,000–3,400,000

450,000

70,000

32.7 ± 0.2

10% Pentastarch

10,000–1,000,000

280,000

39,000

6% Dextran 70

15,000–160,000

70,000

39,000

61.7 ± 0.5

Oxypolygelatin

5600–100,000

30,000

22,000–24,000

45–47

Oxyglobin

64,000–500,000

200,000

—

43.3 ± 0.1

Da = dalton a The weight average molecular weight reﬂects viscosity. It accounts for particle size and is therefore exaggerated by the larger particles. b The number average molecular weight is the total weight divided by the number of molecules. Oncotic pressure is determined by the number of particles, not particle size; therefore, this number is a reﬂection of oncotic pressure. The weight average molecular weight is most commonly used in clinical settings. c As measured on a colloid osmometer.

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Limited Fluid Volume Resuscitation CE Hg may be warranted in patients with active hemorrhage during LFVR. It is important to follow colloids with crystalloids because colloids produce a state of relative dehydration in the interstitial space. Colloids can reduce the requirement for maintenance crystalloids by 40% to 60%.42 The disadvantages of using synthetic colloids include cost, increased risk of volume overload compared with crystalloids, potential for anaphylaxis, potential exacerbation of coagulopathies, and interference with crossmatching. However, these side effects are rarely seen clinically in veterinary patients receiving recommended doses.34,35 Although often recommended in the treatment of patients with increased capillary permeability, colloids may contribute to the development of edema in animals with vasculitis if the large colloid molecules leak into the interstitial space.11 This is a controversial issue and the topic of ongoing studies. The effect of colloids on coagulation is likewise controversial, and studies have yielded inconsistent results.43–45 The hemostatic effects of hydroxyethyl starches are dose dependent and more common with products that have higher molecular weights, a greater degree of substitution (more hydroxyl groups per glucose unit in the molecule), and higher C2/C6 ratios (more hydroxyl groups on the glucose molecule at carbon position 2 compared with position 6).46 Studies have shown decreases in circulating von Willebrand’s factor and factor VIII, increases in activated partial thromboplastin time (APTT), and hypocoagulable changes on a thromboelastogram with the use of higher doses of these products.46,47 Thrombocytopathia has also been reported with the use of hydroxyethyl starches due to blocking of the glycoprotein IIb/IIIa receptor, which is required for platelet activation.48 Overall, when used at recommended doses, synthetic colloids have not been associated with clinical signs of bleeding or clinically signiﬁcant alterations in platelet counts, prothrombin time, APTT, or buccal mucosal bleeding time. Clinical bleeding appears to be rare if doses do not exceed 20 mL/kg/day. However, if massive amounts of synthetic colloids are required for stabilization, concomitant administration of blood products may be warranted to reduce the risk of dilutional coagulopathies.34

Hydroxyethyl Starches Hydroxyethyl starches are highly branched polysaccharides primarily consisting of amylopectin (e.g., hetastarch [HES], pentastarch, tetrastarch). HES is available as a 6% solution in 0.9% sodium chloride (Hespan, B. Braun Medical, Inc.) or as a 6% solution in a lactated electrolyte solution (Hextend, Hospira, Inc.), which is intended to mimic the principal ionic constituents of normal plasma. Compared with isotonic crystalloids, smaller volumes of HES can normalize and maintain SAP without lowering COP. Rapid administration of boluses may cause nausea in cats, and some experts recommend giving HES at a slower rate in this species.11 The smaller particles in HES are almost immediately excreted in urine, whereas the larger particles are absorbed by the liver and spleen and slowly returned to the circulation for up to 36 hours. The larger molecules are degraded by the reticuloendothelial system and excreted by the liver and kidneys several days later.34 HES can also reverse changes in microvascular permeability caused by oxygen free radicals during reperfusion injury, decrease leukocyte-endothelial cell adhesion, and improve microcirculation.49 Pentastarch is available in a 10% solution in 0.9% sodium chloride (Pentaspan, B. Braun Medical, Inc). It is used as a volume-expanding and hemodiluting agent in leukopheresis. In theory, its branched shape may help to plug gaps between separated endothelial cells. Recommended doses of pentastarch are similar to those for HES.34 Tetrastarch is available in a 6% solution in 0.9% sodium chloride (Voluven, Hospira, Inc.). It has a lower molecular weight and degree of substitution than HES and, therefore, causes fewer alterations in coagulation. However, its half-life is shorter, possibly necessitating more frequent dosing. Recommended dosing in people is up to 50 mL/kg/day, although amounts up to 70 mL/kg/day have been used in a research setting without adverse effects.46,47

QuickNotes Overall, when used at recommended doses, synthetic colloids have not been associated with clinical signs of bleeding or clinically signiﬁcant alterations in platelet counts, prothrombin time, APTT, or buccal mucosal bleeding time.

Dextrans Dextrans are macromolecular polysaccharides produced by bacterial fermentation of sucrose. Dextran 70 (6% in 0.9% sodium chloride) is beneﬁcial in reperfusion injury because it decreases neutrophil–endothelial interactions. Dosing of dextran 70 is similar to that of HES,

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and life-threatening allergic reactions to dextran 70 in dogs are extremely rare.42 Dextran 70 can elevate blood glucose concentrations due to metabolism of the dextran. It has been associated with decreased platelet adhesion and reduction of factor VIII complex activity when very large volumes are infused rapidly for acute plasma volume expansion.43

Oxypolygelatin

QuickNotes Many studies have shown that HS with or without a colloid is superior to the use of crystalloids alone for resuscitation, but others have shown no beneﬁt.

A gelatin colloid plasma expander produced from bovine bone marrow (oxypolygelatin) is available, but information about its clinical use is limited. The volume of expansion is double the administered amount, and the clinical effect lasts for 2 to 4 hours.11 Histamine- and complement-mediated allergic reactions and increases in APTT have been reported with its use, but signs of clinical bleeding have not. In one study, oxypolygelatin caused fewer hemostatic abnormalities compared with dextran 70 when administered to healthy dogs.45 Oxypolygelatin can signiﬁcantly lower serum calcium levels and is currently marketed with supplemental calcium. The manufacturers recommend extreme caution with oxypolygelatin use in animals with coagulation defects, hypoproteinemia, cardiac or pulmonary insufﬁciency, or renal disease. Due to its small particle size, side effects, and short duration of action, this product is unlikely to gain widespread use versus other synthetic colloids.

Hemoglobin-Based Oxygen Carriers

shock, hemorrhagic shock, and isovolemic hemodilution. They may also be clinically indicated in the treatment of acute, severe anemia when compatible blood is not readily available or in septic patients to increase oxygen delivery. In animal models of severe, uncontrolled hemorrhage, HBOC infusions resulted in rapid resuscitation and survival with superior cardiac output and oxygen delivery compared with isotonic crystalloids.51 Oxyglobin (Biopure) is an ultrapuriﬁed, polymerized hemoglobin solution of bovine origin in a modiﬁed lactated Ringer’s solution that is used in veterinary patients. It is approved for one-time use in dogs but should be avoided in animals that are predisposed to volume overload.50 A retrospective study on the use of Oxyglobin in cats revealed a high incidence of pleural effusion and pulmonary edema, likely due to acute circulatory overload; therefore, use in cats remains off-label.52 Oxyglobin has been suggested for preoperative use in animals with hemoperitoneum to maximize perfusion as part of an LFVR protocol. Approximately 2 to 4 mL/kg is administered with lower doses of crystalloids to raise the SAP just to 80 to 90 mm Hg while minimizing the risk of dislodging clots.53 Side effects of Oxyglobin can include discoloration of mucous membranes, sclera, and urine; mild gastrointestinal upset; and an increase in central venous pressure. Because Oxyglobin has such a strong colloidal pull, concurrent use of synthetic colloids is not recommended. In addition, some clinical laboratory values are temporarily immeasurable after its use, depending on the type of analyzer used. However, Oxyglobin does not interfere with complete blood cell counts, blood typing, co-oximetry, or blood gas analysis.50

Hemoglobin binds pulmonary oxygen and transports it to tissues, where it is offloaded to the cells. HBOCs improve oxygen delivery to tissues by increasing hemoglobin levels and circulating volume via colloidal pull. On a gram-for-gram basis, HBOC hemoglobin is more potent than erythrocyte hemoglobin at Research in Limited Fluid delivering oxygen to tissues because the mol- Volume Resuscitation ecules are smaller than erythrocytes and are In 1980, it was found that HS resuscitated able to pass through the microcirculation more 100% of dogs in hemorrhagic shock with rapid readily. It is thought that HBOCs scavenge nitric normalization of MAP, acid–base status, and oxide in the blood, causing vasoconstriction cardiac output.4 Since then, multiple studies and increasing systemic vascular resistance.50 have investigated the use of LFVR in hemorThey allow administration of an effective col- rhagic shock. Many studies have shown that loid and oxygen carrier without blood typing HS with or without a colloid is superior to the or crossmatching and can be stored at room use of crystalloids alone for resuscitation,1–10 temperature for long periods of time. In veteri- but others have shown no benefit.54–56 Despite nary medicine, HBOCs have been investigated many encouraging findings, strong experimostly for use during canine hypovolemic mental evidence is still lacking due to con-

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Limited Fluid Volume Resuscitation CE flicting results, and there are few prospective veterinary clinical studies. Many of the LFVR studies conducted to date were retrospective and nonstandardized and used animal models of controlled hemorrhage. These studies measured values such as volume expansion or intraabdominal blood loss, not clinically important values such as end points of resuscitation or overall survival. More recent studies1,57 have used more realistic animal models with uncontrolled hemorrhagic shock. However, it is challenging to find a humane and clinically realistic long-term method of analgesia that does not interfere with cardiovascular responses.1,57 It is hard to apply human clinical and experimental evidence to veterinary patients. For example, in some human studies of LFVR, the elapsed time from a traumatic event to arrival in the operating room was less than 30 minutes, which often is not feasible in veterinary situations. In veterinary patients with nontraumatic hemorrhage, such as a ruptured hemangiosarcoma, surgery is often delayed for much longer than 30 minutes, and employing a hypotensive or delayed fluid resuscitation technique would prolong hypotension and promote multiple organ dysfunction. Furthermore, some veterinary patients with intraabdominal hemorrhage achieve spontaneous hemostasis and do not require surgery. Multiple veterinary studies of hemorrhagic shock have shown that resuscitation with HS and 6% dextran (HS/D) returned hemodynamic parameters to baseline more rapidly than large volumes of crystalloids.4,9 In addition, the HS/D groups consistently maintained better MAP, cardiac output, and oxygen delivery with superior recovery of splanchnic hemodynamics versus animals receiving crystalloids alone.4,9 In studies of dogs with gastric dilatation–volvulus,7–9 the HS/D groups maintained higher cardiac output and oxygen delivery than the isotonic crystalloid groups. In addition, treatment time was significantly reduced, limiting the period of shock, gastric ischemia, and technical staff involvement. However, there was no significant difference in overall survival between

the two groups. In a study comparing HS/D to 0.9% sodium chloride and dextran in swine with severe endotoxic shock, the cardiac output, portal blood flow, intestinal mucosal blood flow, and overall survival were significantly higher in the HS/D group.6 Conversely, studies using animal models of controlled hemorrhage comparing LFVR with resuscitation using crystalloids alone have found no hemodynamic benefit, and some report no difference in blood loss or blood pressure between the groups.54–56 However, increased intraabdominal bleeding and shortened survival time were reported with the use of increasing volumes of lactated Ringer’s solution, and significant improvement in oxygen delivery was reported with the use of LFVR.54–56 A review of studies in animal models found that LFVR appeared to reduce the risk of death in animal models of severe hemorrhage but increased the risk of death in animals with less severe hemorrhage. However, it also found that hypotensive resuscitation reduced the risk of death in all the trials in which it was used.10 Overall, some of the results are promising, but more research is needed in the veterinary community.

Conclusion Clinically, LFVR using HS and colloids is a safe and highly effective alternative to use of crystalloid fluid alone for resuscitation in hypovolemic shock. Previously healthy animals that sustain catastrophic hemorrhage, pulmonary contusions, or traumatic brain injury may benefit most. The use of HS with colloids is superior to the use of isotonic crystalloids alone for vascular volume expansion and may expedite stabilization of hemodynamic parameters while reducing the risk of rebleeding and edema in the lungs and brain. HS may also have immunomodulating and other beneficial properties that alternative fluids do not have. It is important to note that these recommendations apply only to initial shock resuscitation. Treatment must be individualized, and many animals will benefit from combination therapy. Continued research in LFVR is needed in veterinary medicine.

QuickNotes Clinically, LFVR using HS and colloids is a safe and highly effective alternative to use of crystalloid ﬂuid alone for resuscitation in hypovolemic shock.

References 1. Varela JE, Cohn SM, Diaz I, et al. Splanchnic perfusion during delayed, hypotensive, or aggressive ﬂuid resuscitation from uncontrolled hemorrhage. Shock 2003;20(5):476-480. 2. Shackford SR, Sise MJ, Fridlund PH, et al. Hypertonic sodium lactate versus lactated Ringer’s solution for intravenous ﬂuid therapy

in operations on the abdominal aorta. Surgery 1983;94(1):41-51. 3. Wade CE, Grady JJ, Karmer GC. Efﬁcacy of hypertonic saline dextran ﬂuid resuscitation for patients with hypotension from penetrating trauma. J Trauma 2003;54(5):S144-S148. 4. Velasco IT, Ontieri V, Rocha e Silva M, Lopes OU. Hyperosmotic NaCl

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FREE CE Limited Fluid Volume Resuscitation

and severe hemorrhagic shock. Am J Physiol 1980;239:H664-H673. 5. Oi Y, Aneman A, Svensson M, et al. Hypertonic saline-dextran improves intestinal perfusion and survival in porcine endotoxin shock. Crit Care Med 2000;28(8):2834-2850. 6. Schertel ER, Allen DA, Muir WW, Hansen BD. Evaluation of a hypertonic sodium chloride/dextran solution for treatment of traumatic shock in dogs. JAVMA 1996;208(3):366-370. 7. Allen D, Schertel E, Muir WW 3rd, Valentine AK. Hypertonic saline/dextran resuscitation of dogs with experimentally induced gastric dilatation-volvulus shock. Am J Vet Res 1991;52(1):92-96. 8. Schertel ER, Allen DA, Muir WW, et al. Evaluation of hypertonic saline-dextran solution for treatment of dogs with shock induced gastric dilatation-volvulus. JAVMA 1997;210(2):226-230. 9. Chiara O, Pelosi P, Brazzi L, et al. Resuscitation from hemorrhagic shock: experimental model comparing normal saline, dextran, and hypertonic saline solutions. Crit Care Med 2003;31(7):1915-1922. 10. Mapstone J, Roberts I, Evans P. Fluid resuscitation strategies: a systematic review of animal trials. J Trauma 2003;55(3):571-589. 11. Rudloff E, Kirby R. Fluid therapy—crystalloids and colloids. Vet Clin North Am Small Anim Pract 1998;28(2):297-328. 12. Rudloff E, Kirby R. Colloid and crystalloid resuscitation. Vet Clin North Am Small Anim Pract 2001;31(6):1207-1229. 13. Bickell WH, Wall MJ, Pepe PE, et al. Immediate versus delayed fluid resuscitation for hypotensive patients with penetrating torso injuries. N Engl J Med 1994;331(17):1105-1109. 14. Kreimeier U, Lackner CK, Pruckner S, et al. [Permissive hypotension in severe trauma.] Anaesthesist 2002;51(10):787-799. 15. Haskins S. Management of septic shock. JAVMA 1992;200(12): 1915-1924. 16. Hackner SG. Emergency management of traumatic pulmonary contusions. Compend Contin Educ Pract Vet 1995;17(5):677-686. 17. Guyton AC, Hall JE. The microcirculation and the lymphatic system: capillary fluid exchange, interstitial fluid, and lymph flow. In: Guyton AC, Hall JE, eds. Textbook of Medical Physiology. 10th ed. Philadelphia: WB Saunders; 2000:2-8. 18. Dibartola SP. Disorders of sodium: hypernatraemia and hyponatraemia. J Feline Med Surg 2001;3(4):185-187. 19. Gosling P. Salt of the earth or a drop in the ocean? A pathophysiological approach to fluid resuscitation. Emerg Med J 2003;20:306-315. 20. Pascual JL, Khwaja LA, Chaudhury P, et al. Hypertonic saline and the microcirculation. J Trauma 2003;54(5):S133-S140. 21. Angle N, Cabello-Passini R, Hoyt DB, et al. Hypertonic saline infusion: can it regulate human neutrophil function? Shock 2000;14:503508. 22. Sun LL, Ruff P, Austin B, et al. Early up-regulation of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 expression in rats with hemorrhagic shock and resuscitation. Shock 1999;11:416-422. 23. Angle N, Hoyt DB, Coimbra R, et al. Hypertonic saline resuscitation diminishes lung injury by suppressing neutrophil activation after hemorrhagic shock. Shock 1998;9:164-170. 24. Coimbra R, Hoyt DB, Junger WG, et al. Hypertonic saline resuscitation decreases susceptibility to sepsis after hemorrhagic shock. J Trauma 1997;42:602-607. 25. Leonard SE, Kirby R. The role of glutamate, calcium and magnesium in secondary brain injury. J Vet Emerg Crit Care 2002;12(1):17-32. 26. Roche-e-Silva M, Poli de Figueiredo LF. Small volume hypertonic resuscitation of circulatory shock. Clinics (Sao Paulo) 2005;60(2):159-172. 27. Herold LV, Devey JJ, Kirby R, et al. Clinical evaluation and management of hemoperitoneum in dogs. J Vet Emerg Crit Care 2008;18(1): 40-53. 28. Pinto FC, Capone-Neto A, Prist R, et al. Volume replacement with lactated Ringer's or 3% hypertonic saline during combined experimental hemorrhagic shock and traumatic brain injury. J Trauma 2006;60(4):758-763. 29. Vassar MJ, Fischer RP, O’Brien PE, et al. A multicenter trial for resuscitation of injured patients with 7.5% sodium chloride. The effect of added dextran 70. The Multicenter Group for the Study of Hypertonic Saline in Trauma Patients. Arch Surg 1993;128(9):1003-1011. 30. Proulx P, Dhupa N. Severe brain injury: part I pathophysiology. Compend Contin Educ Pract Vet 1998;20(8):897-905. 31. Proulx P, Dhupa N. Severe brain injury: part II therapy. Compend Contin Educ Pract Vet 1998;20(9):993-1006. 32. Qureshi AI, Suarez JL. Use of hypertonic saline solutions in the

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treatment of cerebral edema and intracranial hypertension. Crit Care Med 2000;28(9):3301-3313. 33. Syring RS. Assessment and treatment of central nervous system abnormalities in the emergency patient. Vet Clin North Am Small Anim Pract 2005;35(2):343-358. 34. Day TK, Bateman S. Shock syndromes. In: Dibartola SP, ed. Fluid, Electrolytes and Acid-Base in Small Animal Practice. 3rd ed. St. Louis: WB Saunders; 2006:540-564. 35. Ford S, Schaer M. Shock syndromes in cats. Compend Contin Educ Pract Vet 1993;15(11):1517-1526. 36. Sondeen JL, Coppes VG, Holcomb JB. Blood pressure at which rebleeding occurs after resuscitation in swine with aortic injury. J Trauma 2003;55(4):S110-S117. 37. Friedman Z, Berkenstadt H, Preisman S, Perel A. A comparison of lactated Ringer’s solution to hydroxyethyl starch 6% in a model of severe hemorrhagic shock and continuous bleeding in dogs. Anesth Analg 2003;96:39-45. 38. Stern SA, Dronen SC, Wang X. Multiple resuscitation regimens in a near-fatal aortic injury hemorrhage model. Acad Emerg Med 1995;2(2):89-97. 39. Rozanski E, Rondeau M. Choosing fluids in traumatic hypovolemic shock: the role of crystalloids, colloids, and hypertonic saline. JAAHA 2002;38(6):499-501. 40. Rudloff E, Kirby R. The critical need for colloids: selecting the right colloid. Compend Contin Educ Pract Vet 1997;19(7):811-826. 41. Chan DL, Freeman LM, Rozanski EA, et al. Colloid osmotic pressure of parenteral nutrition components and intravenous fluids. J Vet Emerg Crit Care 2001;11(4):269-273. 42. Rudloff E, Kirby R. The critical need for colloids: administering colloids effectively. Compend Contin Educ Pract Vet 1998;20(1):27-43. 43. Zoran DL, Jergens AE, Riedesel DH, et al. Evaluation of hemostatic analytes after use of hypertonic saline combined with colloids for resuscitation of dogs with hypovolemia. Am J Vet Res 1992;53(10):1791-1796. 44. Deusch E, Gamsjager T, Kress HG, Kozek-Langenecker SA. Binding of hydroxyethyl starch molecules to the platelet surface. Anesth Analg 2003;97(3):680-683. 45. Glowaski MM, Moon-Massat PF, Erb HN, Barr SC. Effects of oxypolygelatin and dextran 70 on hemostatic variables in dogs. Vet Anaesth Analg 2003;30(4):202-210. 46. Cada DJ, Levien T, Baker DE. Hydroxyethyl starch 130/0.4. Hosp Pharm 2008;43(5):396-408. 47. Gandhi SD, Weiskopf RB, Jungheinrich C, et al. Volume replacement therapy during major orthopedic surgery using Voluven® (hydroxyethyl starch 130/0.4) or Hetastarch. Anesthesiology 2007;106(6):1120-1127. 48. Wierenga JR, Jandrey KE, Haskins SC, et al. In vitro comparison of the effect of two forms of hydroxyethyl starch solutions on platelet function in dogs. Am J Vet Res 2007;68(6):605-609. 49. Zikria BA, Subbarao C, Oz MC, et al. Macromolecules reduce abnormal microvascular permeability in rat limb ischemia-reperfusion injury. Crit Care Med 1989;17(12):1306. 50. Day TK. Current development and use of hemoglobin-based oxygencarrying (HBOC) solutions. J Vet Emerg Crit Care 2003;13(2):77-93. 51. Malhotra AK, Kelly ME, Miller PR, et al. Resuscitation with a novel hemoglobin-based oxygen carrier in a swine model of uncontrolled perioperative hemorrhage. J Trauma 2003;54(5):915-924. 52. Gibson GR, Callan MB, Hoffman V, Giger U. Use of hemoglobinbased oxygen-carrying solution in cats: 72 cases (1998-2000). JAVMA 2002;221(1):96-102. 53. Wall RE, Day TK, Mott J, et al. Oxygen-carrying fluids: clinical application of Oxyglobin solution. Compend Contin Educ Pract Vet 1999;21(8 suppl):1-20. 54. Hatoum O, Bashenko, Y, Hirsh M, et al. Continuous fluid resuscitation and splenectomy for treatment of uncontrolled hemorrhagic shock after massive splenic injury. J Trauma 2002;52(2):253-257. 55. Varicoda EY, Poli de Figueiredo LF, Cruz RJ Jr, et al. Blood loss after fluid resuscitation with isotonic or hypertonic saline for the initial treatment of uncontrolled hemorrhage induced by splenic rupture. J Trauma 2003;55(1):112-117. 56. Bruscagin V, de Figueiredo LF, Rasslan S, et al. Fluid resuscitation improves hemodynamics without increased bleeding in a model of uncontrolled hemorrhage induced by iliac artery tear in dogs. J Trauma 2002;52(6):1147-1152. 57. Shoemaker WC, Peitzman AB, Bellamy R, et al. Resuscitation from severe hemorrhage. Crit Care Med 1996;24(2S):12-23.

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Limited Fluid Volume Resuscitation CE

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 healthy cats and dogs, how much of the body’s total fluid is within the intravascular space? a. 8.25% b. 12% c. 15% d. 33% 2. When isotonic crystalloids are used alone for fluid resuscitation, approximately how much of the administered fluid remains within the intravascular space after 1 hour? a. <20% b. 33% c. 50% d. 75% 3. In clinical studies, higher doses of synthetic colloids caused all of the following hemostatic changes except a. decreased von Willebrand factor antigen. b. decreased factor VIII. c. increased APTT. d. decreased platelet count. 4. Which statement regarding synthetic colloids is true? a. They are considered to have double the

potency of crystalloids for intravascular volume support per milliliter. b. They are used clinically in doses of 5 to 50 mL/kg/day. c. They expand intravascular volume by increasing the COP. d. They can make dogs vomit when given rapidly. 5. The recommended dose of 7.2% HS for an animal in shock is ________ mL/kg. a. 1 to 2 b. 3 to 8 c. 10 to 20 d. 55 to 60 6. HS is not contraindicated in which condition? a. dehydration b. traumatic brain injury c. heart failure d. renal failure 7. Approximately how long do the resuscitative effects of 7.2% HS alone last? a. <15 min b. <30 min c. 60 min d. 1 to 3 hr

8. Which is not a beneﬁt of HS administration? a. an increased extracellular glutamate level b. an increased extracellular sodium concentration c. promotion of local vasodilation and microcirculatory blood ﬂow d. inhibition of the coagulation cascade 9. Which statement regarding HS–colloid combinations is true? a. They remain effective in the vascular space for 2 to 3 hours. b. They can be mixed and given simultaneously. c. They should not be given faster than 1 mL/kg/min. d. all of the above 10. Which statement regarding Oxyglobin is true? a. It is approved for use in dogs and cats. b. It requires blood typing and crossmatching before use. c. It will not interfere with any laboratory testing. d. It should be avoided in animals predisposed to volume overload.

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Research Recap

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Selected abstract from Veterinary Therapeutics

Demonstration of 1-Year Duration of Immunity for Attenuated Bordetella bronchiseptica Vaccines in Dogs* Lehr C, Jayappa H, Erskine J, et al. Vet Ther 2008; 9(4):257-262. Three groups of healthy dogs with low antibody titers to Bordetella bronchiseptica (Bb), canine parainfluenza virus (CPI), and canine adenovirus type 2 (CAV-2) were used in this study. One group was vaccinated with a single dose of monovalent attenuated Bb vaccine and one group with a trivalent vaccine containing attenuated Bb, CPI, and CAV-2; dogs were vaccinated intranasally FFrom th the with a single dose of the Winter 2008 issue respective vaccines. The third group served as an unvaccinated control. All vaccinated dogs subsequently developed serum antibody titers to Bb that persisted for at least 1 year. Following Bb challenge 1 year after vaccination, all vaccinated dogs, regardless of group, showed significantly fewer clinical signs and shed significantly fewer challenge organisms than unvaccinated controls. These results demonstrate that intranasal administration of a single dose of monovalent attenuated Bb vaccine or trivalent vaccine containing attenuated Bb, CPI, and CAV-2 provides 1 year of protection against Bb. *This research was sponsored by Intervet/Schering-Plough Animal Health, Elkhorn, Nebraska.

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Regulation Pet Foods of

❯❯ David A. Dzanis, DVM, PhD, DACVNa Dzanis Consulting & Collaborations Santa Clarita, California

in the United States

Abstract: In the United States, pet foods (including treats, edible chews, and supplements) are subject to regulation at both federal and state levels. Products found to be adulterated or misbranded are subject to enforcement action. Veterinarians play a key role in helping ensure pet food safety by reporting possible adverse effects to authorities in a timely manner. n 2007, the widely reported recall of dog and cat foods due to contamination with melamine and related compounds brought renewed public scrutiny of the pet food industry. The Internet is replete with sites that disparage the nutritive value and safety of commercial pet food products, often implicating poor regulatory oversight. Because pet owners often consult veterinarians on matters relating to pet food, it behooves practitioners to be familiar with the topic of pet food regulation.

Who Regulates Pet Foods?

At a Glance Who Regulates Pet Foods? Page 324

Government Oversight of Pet Foods Page 326

Oversight of Veterinary-Dispensed Products Page 326

The Veterinarian’s Role Page 327

324

The US Department of Agriculture oversees meat and poultry products intended for human consumption; however, the same products, intended for animal consumption, fall within the authority of the US Food and Drug Administration (FDA). FDA’s Center for Veterinary Medicine has primary jurisdiction over all animal feed in interstate commerce (including imports).1 “Animal feed” includes pet food, which further encompasses complete and balanced foods, treats and snacks, supplements, edible chews (e.g., rawhides, bones), and the ingredients intended to be incorporated into these products. “Interstate commerce” of a product is determined by the a

Dr. Dzanis is a consultant for the pet food and related industries on matters pertaining to nutrition, labeling, and regulation. He formerly served as the veterinary nutritionist for the US Food and Drug Administration and represented the agency on the Association of American Feed Control Ofﬁcials Pet Food Committee.

origins of its ingredients, the location where the product was manufactured, and the point of sale or receipt of the product. Most pet foods contain at least some ingredients obtained from sources outside of the state where they are manufactured; therefore, virtually all pet foods fall under federal authority. Individual state governments also exercise authority over animal feed and pet food distributed within their jurisdiction. This constitutes another layer of regulatory oversight that is more extensive than is required for most human food items. Each state’s laws and regulations are enforced by the state feed control official, typically an employee in the state’s department of agriculture or chemist’s office. While the acronym AAFCO commonly appears on “complete and balanced” dog and cat food labels, few in the public understand the nature and role of the Association of American Feed Control Officials (AAFCO) in pet food regulation. AAFCO is neither a government body empowered to act under authority of law nor a trade association whose goal (as ascribed by its critics) is to mitigate the impact of regulation on industry. Rather, it is a private body wholly comprised of federal, state, and foreign gov-

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CONTRIBUTED BY THE AMERICAN COLLEGE OF VETERINARY NUTRITION About ACVN ernment officials.2 Essentially, its role is to provide a Model Bill and Regulations, establish ingredient definitions, and set other standards (such as guidelines for use of the term natural and the AAFCO Dog and Cat Nutrient Profiles and feeding trial protocols), via policy or guidance, that represent a consensus among regulators about what constitutes the appropriate regulation of animal feed. Nothing AAFCO publishes has any power of law unless subsequently adopted by individual state legislatures, and not all states follow AAFCO models. However, enough do that AAFCO has nationwide influence.

Representatives of industry and consumer groups can provide information to committees and working groups within AAFCO and are free to voice their opinions at public AAFCO meetings. However, they are not allowed to be members of AAFCO and hence, cannot hold ofﬁce, make motions, or cast votes on any matter under consideration.

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

CompendiumVet.com | July 2009 | Compendium

325

Government Oversight of Pet Foods

With regard to pet food, the federal and state governments’ mandate is to enforce pertinent laws relating to pet food manufacture and distribution. This includes products sold through retail outlets, veterinary clinics, catalogs, and Web sites. The Federal Food, Drug, and Cosmetic Act of 1938 (FFDCA) and equivalent state laws prohibit the distribution of foods that are either adulterated or misbranded.3 The term adulterated may refer to the presence of a chemical, microbiologic, or physical contaminant, including any substance that is not generally recognized as safe, an approved food additive, or an otherwise sanctioned ingredient (e.g., via the AAFCO Feed Ingredient Definition process) for use in pet foods. Failure of a product to meet stated nutrient guarantees or conform to sell pet foods, including veterinary clinics. ingredient or nutritional representations is also Wholesale distribution points within the state a form of adulteration.2 The term misbranded are also subject to inspection. Inspectors may relates to false or misleading claims and to search for products that are not properly reglabeling that is not in compliance with federal istered or have been previously denied sale. or state regulations. “Drug claims,” which are Samples of products may be obtained from defined as claims that a product can (1) treat, the location for label review and/or laboratory prevent, mitigate, or otherwise affect a disease analysis for nutrient content and contaminaor condition or (2) affect the structure or function. Depending on the egregiousness of any tion of the body in a manner beyond what is violations found, the product may be seized normally ascribed to food, for which the prod- by the regulator, or the company may be notiuct is not approved, can be considered a form fied and allowed time to remedy the violation. of misbranding.1 Compared with individual states, FDA conMost enforcement efforts are conducted ducts little direct enforcement. While FDA can by state feed control officials. This is because seize product or take other enforcement meamany state laws (particularly those that follow sures, there are no federal product registration AAFCO models) mandate periodic (usually or company licensure requirements at this time annual) product registration and/or company (except registration of food manufacturing licensure as a condition of distributing in the facilities under the Bioterrorism Act). However, state.2 Typically, the process requires submis- FDA is intimately involved in the process of sion of product labels for review by the feed state enforcement efforts, assisting states with control official. Sale of any product found to scientific, technical, and regulatory experbe misbranded may be denied in that state, tise in support of contemplated enforcement affecting not only distribution of the product actions. For example, feed control officials within the state, but also deliveries from out- often refer questionable claims or ingredients side the state based on catalog or online sales. to FDA for assessment before taking action, or While this action would appear to affect only they may require a company to first obtain one jurisdiction, in practice, it is infeasible for FDA’s acceptance as a condition of distribupet food companies to distribute products in tion of its product in their state. Also, FDA has different states with different labels. Hence, taken direct action when it was deemed more labeling found to be objectionable by one effective than a single state’s action, such as in state may result in revision of the labeling for cases involving catalog and online sales. nationwide sale of a product. In addition to their registration/licensure Oversight of Veterinary-Dispensed Products functions, state feed control officials often Veterinarians frequently dispense therapeutic inspect pet stores and other retail outlets that pet foods as part of normal practice. As noted

QuickNotes State feed control ofﬁcials often inspect pet stores and other retail outlets that sell pet foods, including veterinary clinics.

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above, a pet food label bearing a drug claim is subject to enforcement action. However, FDA often exercises “enforcement discretion” in the case of veterinary therapeutic diets. In other words, it allows companies to convey information to veterinarians on the function of a product as it relates to disease processes, provided that the product is sold under a valid veterinarian/client/patient relationship.4 This discretion is based on the premise that veterinarians’ medical and scientific training is sufficient to enable safe and appropriate use of the product by clients. However, most veterinarians are not aware that the diet/disease claims made by the company most often have not been reviewed and verified by FDA. This is not to imply that such products lack benefit or are unsafe when used as clinically appropriate. On the contrary, manufacturers of therapeutic diets may have extensive documentation. The Veterinary Oral Health Council (VOHC), an organization under the auspices of the American Veterinary Dental College, provides protocols and reviews data from companies with regard to dental plaque and tartar control claims and allows use of its seal of acceptance for products that pass muster in this regard. However, other than VOHC, there are no independent organizations that scrutinize therapeutic diet claims for products sold in the United States. Many veterinarians also distribute pet supplement products to clients. The Dietary Supplement Health and Education Act of 1994 (DSHEA) diminished FDA’s authority over dietary supplements (a subcategory of foods) by allowing the inclusion of ingredients that were previously prohibited in food products as well as broadening the scope of permissible

claims relating to function. This act affects only products that meet the statutory definition of dietary supplements, not foods in “conventional” form. Regardless, FDA has given notice of its determination that DSHEA only applies to products intended for human consumption, so that FFDCA still applies to all pet products, whether in conventional (e.g., a complete and balanced pet food) or supplement (i.e., “dosage”) form.5 In response, some manufacturers of pet supplement products containing unapproved food additives (such as many herbs, botanicals, metabolites, and other compounds) have opted for labeling such products as drugs rather than as foods. While still under the authority of FDA and “animal remedy” laws in some states, products so labeled may escape scrutiny by many state feed control officials. Further, although FDA does allow some products on the market as “unapproved drugs of low regulatory priority” based on its determination of reasonable expectations of safety, it is not obvious by their labeling which products have passed FDA muster in this regard and which have not. As a result, some products on the market may not have received adequate review by regulatory officials.

The Veterinarian’s Role Notwithstanding the adverse attention pet foods have received since the 2007 recall, in general, pet foods have a good safety record.6 Regardless, future contamination incidents are always possible. Clinicians are in an excellent position to detect and report potential pet foodborne illness before a larger outbreak occurs. Suspected or conﬁrmed contamination should be reported to appropriate regulatory agencies (TABLE 1)

QuickNotes FDA often exercises “enforcement discretion” in the case of veterinary therapeutic diets.

TABLE 1

Reporting Suspected or Conﬁrmed Pet Food Contamination or Adverse Eventsa

Whom to Contact

How to Contact

Alternate Contact Method

Pet food manufacturer

Call “800” telephone number on label.

Visit company Web site.

FDA

Call your FDA district ofﬁce consumer complaint coordinator. Telephone numbers for district ofﬁces are listed at fda.gov/opacom/ backgrounders/complain.html.

Call the telephone number listed in the blue pages (for federal agencies) in the telephone directory.

State feed control ofﬁcial (state agency varies but is usually the department of agriculture or chemist’s ofﬁce)

Call an AAFCO member in your state. Telephone numbers are listed in the AAFCO membership directory at www.aafco.org/Directory/ MembershipDirectory/tabid/62/Default.aspx.

Call the telephone number listed in the blue pages (for state agencies) in the telephone directory.

Dzanis DA. Anatomy of a recall. Topics Companion Anim Med 2008;23(3):133-136. Reproduced with permission.

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QuickNotes Veterinarians must practice due diligence in assessing the clinical need for a given supplement in an individual animal.

as well as the manufacturer, which may be in the best position to recognize a pattern of complaints suggesting a safety problem. Pertinent information to relate to regulators and companies includes the product name (including variety) and package size, as well as the universal product code (UPC) number to help identify the exact product in question. Regulators and companies can also use lot or date codes to help pinpoint the production batch(es) of highest concern. The date and place of purchase of the suspect food, as well as relevant medical information regarding the animal, are also helpful. Proper handling of samples of the suspect food as legal evidence may be critical if there is a possibility of a lawsuit at a later date.6 Therapeutic pet foods must meet the same processing, ingredient, and labeling standards as any other pet food, including substantiation of nutritional adequacy. A food labeled “This product is intended for intermittent or supplemental feeding only” should not be considered sufﬁcient for long-term feeding as the sole source of nutrition. In consideration of the lack of regulatory review of efﬁcacy

claims for therapeutic diets, it is prudent for clinicians to carefully scrutinize data supplied by companies in support of the reported beneﬁts of their products. Outcomes of feeding these diets should be closely monitored. Before using or recommending any supplement product, veterinarians must practice due diligence in assessing the clinical need for a given supplement in an individual animal; evaluating the strength, quality, and source of data to support the use of the supplement; and judging the integrity and competence of the manufacturer. Veterinarians must also objectively assess outcomes of supplement administration and be open to revising use or recommendations as necessary. Any observed adverse effects should be reported to the appropriate regulatory ofﬁcials as well as the manufacturer. Members of the National Animal Supplement Council (NASC)—a trade organization representing the interests of supplement manufacturers—that receive adverse event reports must convey that information to the council to be included in its database.7 NASC allows federal and state regulators, but not the general public, to review this database.

References 1. Benz SA. FDA’s regulation of pet food. Accessed December 2008 at fda.gov/cvm/petfoodflier.html. 2. 2008 AAFCO Official Publication. Oxford, IN: Association of American Feed Control Officials; 2008. 3. Federal Food, Drug, and Cosmetic Act. Washington, DC: Government Printing Office; 1999. 4. Intended use of therapeutic diets as drugs dictates VCPR requirement. JAVMA 2003;222(7):923.

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5. Inapplicability of the Dietary Supplement Health and Education Act to Animal Products. Federal Register 1996;61(78):17706-17708. 6. Miller EP, Cullor JS. Food safety. In: Hand MS, Thatcher CD, Remillard RL, Roudebush P, eds. Small Animal Clinical Nutrition. 4th ed. Topeka, KS: Mark Morris Institute; 2000:183-198. 7. National Animal Supplement Council. Frequently asked questions. Accessed December 2008 at: nasc.cc/index.php?option=com_ content&task=view&id=29&Itemid=38.

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Abstract Thoughts Offering a brief look at the latest important research presented in the international veterinary literature.

Intussusception After Methiocarb Toxicosis in Dogs Corﬁeld GS, Connor LM, Swindells KL, et al. Intussusception following methiocarb toxicity in three dogs. J Vet Emerg Crit Care 2007;18:68-74.

Column Editor ❯❯ Joseph Harari, MS, DVM, DACVS Veterinary Surgical Specialists Spokane, Washington

TO LEARN MORE Take CE tests Access full-text articles Watch videos You can find these at

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Methiocarb, a common carbamate molluscicide, causes toxicosis in dogs. This study reports details of three cases involving dogs that ingested slug and snail bait pellets, suffered methiocarb toxicosis, and underwent treatment. The purpose was to report intussusception as a complication and suggest possible risk factors. The dogs were an 18-week-old German shepherd mix, a 5-month-old Staffordshire bull terrier, and an 8-month-old German shepherd. Toxicosis was diagnosed on the basis of access, clinical signs, and the presence of blue molluscicide in gastric fluid and feces. Treatments involved intravenous fluids, diazepam, emesis, gastric lavage, enema, activated charcoal, and sorbitol. All the dogs had persistent clinical signs of toxicosis despite initial treatment and attempts to eliminate the remaining toxin. Intussusception was diagnosed within 36 and 24 hours in two dogs and after 18 days of treatment for the toxicosis in the third dog. Laparotomy confirmed the diagnosis. Two dogs recovered after supportive care, enterectomy of the affected bowel, and end-to-end anastomosis. Because only three cases were presented, positive identification of the risk factors responsible for intussusception is impossible. However, risk factors discussed included age, incomplete gastrointestinal decontamination, the process of decontamination (using cathartics and anesthetic), and the use of metoclopramide. More detailed epidemiologic studies of methiocarb toxicosis and its association with intussusception are warranted.

Traumatic Urethral Rupture in Cats: Alignment with a Urethral Catheter Meige F, Sarrau S, Autefage A. Management of traumatic urethral rupture in 11 cats using primary alignment with a urethral catheter. Vet Comp Orthop Traumatol 2008;21:76-84.

This study evaluated an alternative to primary urethral repair, which is complex and may cause strictures, in

11 domestic shorthair cats with urethral disruption caused by urethral catheterization to relieve obstruction (eight cats) or trauma (three cats). Retrograde catheterization was achieved in five cats; five others needed cystotomy for catheter placement (one cat was not catheterized because of complete rupture). A CONTINUES ON PAGE 344

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3 CE CREDITS

CE Article #2

Intracranial Meningioma in Dogs and Cats: A Comparative Review ❯❯ Kara Sessums, DVM, DACVIM (Neurology) Veterinary Emergency & Referral Group Brooklyn, New York

❯❯ Christopher Mariani, DVM, PhD, DACVIM (Neurology) North Carolina State University

Abstract: 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 grow slowly and have an insidious onset of clinical signs. These tumors are more likely to be malignant in dogs. Surgery, radiation, and chemotherapy can target the primary tumor, whereas steroids and anticonvulsants are conﬁned to treating secondary effects of the tumor. Surgery is the preferred primary option for cats because the tumor can be excised completely in most cases. If the meningioma cannot be resected in its entirety, radiation therapy can increase survival time.

M At a Glance Clinical Findings Page 330

Pathologic Findings Page 331

Diagnosis Page 332

Treatment Page 334

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eningioma is the most common primary brain tumor in dogs and cats.1,2 Most dogs with brain tumors are older than 5 years, with a median age of 9 years.3 Brain tumors are also a geriatric disease in cats (mean age: 12 years).4 Older male cats seem to be more prone to meningioma, where as dolichocephalic breeds are overrepresented in dogs.3 Today, the increasing availability of veterinary specialists for referral and advanced imaging is facilitating the diagnosis of meningioma. After the diagnosis is established, the decision to treat and the choice of protocol must be considered. In veterinary medicine, treatment issues include the cost, expected survival time, and quality of life. What one client deems acceptable in terms of clinical signs and life span for a pet may not be satisfactory for another client. It is imperative that veterinarians be informed about the most current treatment options and probable survival times so that clients can make the best informed decision for themselves and their pets. As human meningioma treatment evolves, veterinary patients should also beneﬁt from additional, possibly less invasive, treatment options.

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Clinical Findings Meningiomas in cats and dogs typically have an insidious onset of clinical signs due to their slow growth rate. Pet owners may attribute subtle behavior changes to old age; several studies have found that clinical signs of meningiomas are present for an average of 1 to 3 months before diagnosis in cats.5–7 The severity of clinical signs depends on the growth rate and location of the meningioma, peritumoral edema, intracranial pressure, and compensatory mechanisms within the brain. Because meningiomas arise outside of the brain parenchyma, they cause a mass effect as they slowly compress normal brain tissue. If normal compensatory mechanisms are exhausted (i.e., decreased cerebrospinal ﬂuid [CSF] and blood volume), clinical signs can become acutely worse.6 Seizures are by far the most common clinical sign of intracranial meningioma in dogs, with the cerebral hemispheres being the most commonly affected.3,8 Patients can have normal neurologic ﬁndings interictally1; therefore, a brain tumor should be suspected in any dog older than 5 years that presents with a recent onset of seizures. Other clinical signs in dogs include ataxia, blindness, and behavior changes.9

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Intracranial Meningioma in Dogs and Cats CE Seizures can also occur with meningioma in cats but are much less common than in dogs.4,10 Cats can present with decreased vision, ataxia, paresis, circling, or altered consciousness. In two reports on feline intracranial neoplasia,4,10 21% of cats had no speciﬁc neurologic signs but presented with lethargy and anorexia; 22% of cats with brain tumors had seizures. We have seen several geriatric cats in which cerebral meningioma was ultimately diagnosed that had normal neurologic ﬁndings and had presented to several veterinarians for the chief complaint of “just not being themselves” (i.e., behavior change and indolence). Headache, a common symptom in human patients,11 cannot be assessed in animals, but it may explain the large number of dogs and cats that present with lethargy or personality change. Unlike dogs, which typically do have clinical signs, cats can have multiple tumors as well as asymptomatic meningiomas. In cats, intracranial meningioma is a common inciBOX 1

World Health Organization Classiﬁcation of Meningiomas Grade I/Benign Only occasional mitotic ﬁgures Most common Ki-67 index: <4%–5%

dental ﬁnding on necropsy, as many do not display any clinical signs.12–14 In one retrospective review of feline intracranial neoplasia, 22.6% of meningiomas were considered to be incidental.4 Multiple meningiomas in cats can cause multifocal neurologic signs, depending on their location.12,13

Pathologic Findings Meningiomas are thought to arise from the arachnoid cap cells and arachnoid granulations, especially where they project into the dural venous sinuses.6,14 Grossly, canine and feline meningiomas are discrete, ﬁrm, rubbery, lobular, gray to pink, extramedullary masses. Meningiomas are typically well encapsulated (especially in cats) and attached to the underlying dura, displacing the brain without invading it.14–18 However, the edges of canine tumors can be hard to distinguish from edematous brain tissue, and meningiomas are invasive to normal brain tissue in almost 30% of canine cases.1,6 Hyperostosis, or proliferation of the overlying skull in response to pressure from the meningioma, is seen mostly in cats. Meningiomas can be attached to the dura in a broad, pedunculated, or sheet-like fashion (meningioma en plaque).14,16 The World Health Organization (WHO) has established tumor categories and grades for

QuickNotes Seizures are the most common clinical sign of intracranial meningioma in dogs but not in cats.

FIGURE 1

Grade II/Atypical At least four mitotic figures per 10 highpower fields or Meets three of the following criteria: ❯ Increased cellularity ❯ Small cells with a high nucleus:cytoplasm ratio ❯ Prominent nucleoli ❯ Sheet-like growth pattern ❯ Small foci of necrosis ❯ Ki-67 index: 5%–10% Grade III/Anaplastic (Malignant) Obvious malignant cytology (resembles a sarcoma or carcinoma) 20 or more mitotic figures per 10 highpower fields Brain invasion common Ki-67 index: >15%

Immunohistochemical staining of an anaplastic canine meningioma with Ki-67 staining of 19%. Ki-67−positive cells stain brown. CompendiumVet.com | July 2009 | Compendium: Continuing Education for Veterinarians®

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QuickNotes In general, the term benign must be used cautiously when discussing meningiomas in dogs.

human meningiomas (BOX 1).11 Ki-67, a nuclear protein found only in the proliferative phases of the cell cycle, is considered the most reliable proliferative marker for human brain tumors, and its presence is easily demonstrated with immunohistochemical staining (FIGURE 1). The Ki-67 index is useful in determining prognosis and likelihood of recurrence.19 WHO grade I tumors have a low Ki-67 index (<4% to 5%), grade II meningiomas have a moderately high index (5% to 10%), and grade III tumors have the highest index (frequently exceeding 15%).15 Ki-67 was previously reported in canine meningiomas, and we, along with another group, recently conﬁrmed its presence in feline meningiomas.20,21 Although the WHO staging system is not generally used in histologic grading of canine and feline meningiomas, malignant meningiomas have been reported in both species.13,18 Most intracranial meningiomas in cats are benign and relatively easy to remove surgically. By contrast, 18% to 27% of canine meningiomas are malignant and invade the Virchow–Robin space.1,6 In general, the term benign must be used cautiously when discussing meningiomas in dogs. Even though most canine meningiomas are cytologically benign, they can still be considered biologically malignant (likely to kill the animal) because of their increased growth rate and lack of demarcation from normal brain tissue and the difﬁculty in treating them with surgery alone.2 FIGURE 2

Coronal view.

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Another pathologic variant of note in dogs is the cystic meningioma (FIGURE 2). Cysts within a tumor can be caused by tumor necrosis, isolation of CSF, or ﬂuid production by the tumor itself.6 Although reports of canine cystic meningiomas are rare, we have presumptively diagnosed many cystic meningiomas in dogs. Interestingly, these tumors are almost always located in the olfactory lobe of the brain.22 The cyst is often much larger than the tumor mass, and most clinical signs are attributable to increased intracranial pressure secondary to the large quantity of ﬂuid in the cyst.22 In people, meningiomas occur twice as often in women as in men, leading many authors to investigate the role of estrogen and progesterone in their growth.5 Although most human meningiomas have progesterone receptors, and some have estrogen receptors, the function of these receptors is unclear.5,23 A high proportion of progesterone receptors has also been found in canine and feline meningioma cells.24 In both species, lower progesterone expression has been shown to correlate with early recurrence and a high proliferation index.23,25

Diagnosis Meningiomas can be tentatively diagnosed in cats and dogs based on computed tomography (CT) or magnetic resonance imaging (MRI) ﬁndings. The diagnosis requires that the mass be

T1-weighted postcontrast magnetic resonance imaging (MRI) scans of a canine cystic meningioma (arrows).

Axial view. Histologic confirmation was obtained via surgical biopsy. The inner black region is the cystic fluid inside the tumor.

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Intracranial Meningioma in Dogs and Cats CE extraaxial (i.e., outside of the brain parenchyma), erally heterogeneously hyperintense. Postcontrast either with a dural attachment or confined T1-weighted images display the tumor’s distinct strictly within a ventricle.11 However, defini- margins with marked contrast enhancement tive diagnosis requires collection of a tissue because the capillaries of the meningioma do not biopsy sample either during surgery or with a pass through the blood–brain barrier (FIGURE 3). CT-guided stereotactic system. A thorough pre- A dural “tail” enhancement has been described anesthetic work-up, including a complete blood and is another characteristic that raises the index cell count, chemistry panel, urinalysis, thoracic of suspicion for meningioma. However, it is radiography, and abdominal ultrasonography, is impossible to differentiate reactive dural thickenrecommended before CT or MRI. A recent study ing from tumor extension along the dura.27,28 Cysts of intracranial neoplasms in dogs found other, that may be associated with the tumor are best unrelated tumors in 23% of patients at necropsy.8 visualized on T2 weighted images.11 CT and MRI are relatively accurate in providTherefore, it is crucial to rule out metastatic disease or an unrelated primary neoplasm before ing a tentative diagnosis of meningioma in dogs discussing prognosis and treatment options for and cats. One study in dogs29 showed 100% correlation with MRI diagnosis and histopaa presumed meningioma. CT is not as useful for demonstrating soft thology for meningioma. Imaging diagnosis of tissue detail as MRI, but it is usually adequate meningioma included peripheral location, tissue for identifying tumors in the rostral fossa. displacement but not infiltration, increased or When imaging the caudal fossa, CT is much diffuse contrast enhancement, dural thickenmore prone to artifact production secondary ing, and close proximity to the meninges. This to interference from the surrounding petrous study also found that CT correctly identified temporal bone.26 Meningiomas are isodense to the histologic tumor type in 86% of the cases slightly hyperdense, homogenous, and brightly evaluated.29 A similar study in cats28 reported enhanced on CT. Calcification of the menin- correct identification of 96% of brain tumors as gioma is best seen on CT, but if the entire tumor meningiomas based on MRI appearance alone. is densely calcified, no enhancement may be Advanced imaging, such as MRI or CT, has not seen after intravenous administration of con- been shown to determine which canine tumors trast medium (FIGURE 3). Hyperostosis of the are more invasive to normal brain tissue and, overlying skull is easily visualized on CT.11,27 therefore, which tumors may be more difficult On T1-weighted MRI, most meningiomas are to treat with surgery alone. isointense or hypointense compared with gray matCSF characteristics of canine intracranial ter; their appearance on T2-weighted images is gen- meningiomas have been reported. The results

QuickNotes CT and MRI are relatively accurate in providing a tentative diagnosis of meningioma in dogs and cats.

FIGURE 3 Images of a feline meningioma (arrows).

Computed tomography—precontrast transverse view.

MRI—postcontrast sagittal T1-weighted view. Meningioma was confirmed with surgical biopsy.

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Treatment Palliative Treatment

Courtesy of Cheryl Chrisman, DVM

FIGURE 4

Intraoperative photograph after removal of a feline intracranial meningioma. Feline meningiomas are typically well circumscribed and easily differentiated from normal brain parenchyma.

QuickNotes Surgery is the preferred primary therapy for feline patients and is usually successful because most feline tumors can be excised completely.

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are variable; an older study30 found that most CSF had pleocytosis with a predominance of neutrophils. Another author16 theorized that the neutrophils were secondary to focal necrosis of the meningioma with suppuration. A more recent report31 showed that most dogs (73%) did not have pleocytosis but instead had a nucleated cell count of <5/dL of fluid. Total protein levels were increased in the CSF of 61% of the dogs. Spinal fluid analysis can help rule out inflammatory disease as the cause of neurologic signs but is not defi nitive. We prefer not to collect CSF from animals with an intracranial mass consistent with meningioma on MRI, especially if there is significant peritumoral edema and mass effect. Increased intracranial pressure can put the patient at risk for brain herniation after CSF collection.1 Definitive diagnosis of meningioma requires tissue biopsy. This can be performed intraoperatively at the time of tumor removal. A modified CT-guided stereotactic brain biopsy system has been described for use in dogs and is available at several veterinary teaching hospitals. Of 18 dogs with meningiomas, 100% were correctly diagnosed on histopathology using a specimen obtained with this system.32 Postoperative clinical complications were considered mild, and 72% of the dogs recovered from the biopsy procedure with no apparent complications. Biopsy is imperative to confirm the diagnosis of meningioma and provides vital information regarding prognosis and appropriate treatment options.

Palliative therapy targets the secondary effects of the tumor. Typically, an antiinflammatory dose of glucocorticoids is administered to decrease CSF production and tumor-associated brain edema1; this therapy may be required for the lifetime of the patient, depending on what additional definitive therapy is selected by the owner. Steroids decrease the permeability of tumor capillaries as well as tumor blood volume.33 If the meningioma causes seizures, anticonvulsant therapy is also indicated. Phenobarbital and potassium bromide are the anticonvulsants most commonly used in dogs, but many options are available.34,35 Standard doses of phenobarbital given to dogs with rostral forebrain tumors tend to cause profound sedation; this and other side effects of phenobarbital and potassium bromide (e.g., polyuria, polydipsia, polyphagia) are likely to be compounded by concurrent steroid use.1 Cats do not commonly present with seizures, but anticonvulsants are also indicated if seizures develop in this species. Palliation with steroids and anticonvulsants is recommended regardless of whether the owner opts for definitive therapy. Some animals respond significantly to palliative treatment alone; in one study,36 the median survival time was 3.8 months (range: 0.5 to 25.1 months) in dogs treated with anticonvulsants and steroids alone. There are no case reports of survival times for dogs in which no therapy was pursued for meningioma. In our experience, owners who decide against therapy choose to euthanize the dog immediately after diagnosis.

Surgery Surgery is the preferred primary therapy for feline patients and is usually successful because most feline tumors can be excised completely (FIGURE 4). Meningiomas in cats are ﬁrm, well-circumscribed masses that do not usually invade the neural parenchyma and are easily delineated from normal brain tissue.37 Postoperative mortality associated with craniotomy for meningioma removal in cats is reported to be approximately 19%, with anemia being the most common complication.7 In our clinical experience, however, the surgical mortality is close to 0% for cats. In one report,7 surgery as the sole treatment for

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Intracranial Meningioma in Dogs and Cats CE intracranial meningiomas in cats yielded sur- ter prognosis, with median survival times vival rates of 71% at 6 months, 66% at 1 year, exceeding 313, 523, and 1254 days, respecand 50% at 2 years. Another report noted com- tively. Patients with anaplastic and fibroblastic parable results, with 78% of cats having no subtypes had the shortest survival times at 0 tumor recurrence for a median of 27 months.38 and 10 days, respectively.42 Histologic subtypSimilar survival times are reported in cats with ing of meningiomas may eventually be used in multiple meningiomas.12 dogs to determine prognosis and individualize The same is not true for surgical removal of treatment, possibly in conjunction with testing intracranial meningiomas in dogs. Even tumors for Ki-67 levels. This subtyping may not be that are histologically benign are seldom well needed in cats because their tumors seem to encapsulated and are therefore difficult to dis- be more benign in nature. tinguish from the surrounding brain tissue.39 Canine meningiomas tend to be friable, and Radiation almost 33% infiltrate the brain parenchyma.1,11 The ultimate goal of radiation therapy is to In a study evaluating craniotomy in dogs and administer the highest possible dose to the cats,40 the authors specifically commented tumor while minimizing damage to surroundon the differences between canine and feline ing healthy tissue.37,44 Radiation affects cells and tumors. The feline tumors were generally well their vasculature; 80% of the observed clinical defined and easily extracted, whereas the canine effect is due to DNA damage resulting from the meningiomas lacked demarcation from normal ionization of water and production of oxygen brain tissue. Moreover, dogs treated with surgi- free radicals.5 This effect has a latent period cal removal alone had median survival times of and can take months to occur in slow-grow7 and 6.7 months, respectively, in two separate ing meningiomas. The acute adverse effects studies.9,36 Postcraniotomy radiation therapy can of radiation include cerebral edema and, posprolong survival significantly. These same stud- sibly, a temporary increase in seizure activity. ies reported mean survival times of 16.5 and Brain edema, which may be due to transient 16.9 months for meningiomas in dogs treated demyelination, responds to steroid therapy. with tumor resection followed by fraction- Late effects of radiation can be seen months to ated radiation.9,36 Another report found a mean years after therapy and are due to brain necroprogression-free survival interval of 30 months sis. Late effects can mimic the original clinifor incompletely resected canine meningiomas cal signs of the treated tumor and cannot be treated postoperatively with radiation.41 effectively treated.33,45 In veterinary medicine, 42 A recent retrospective study found much however, late effects of radiation therapy are longer survival times in dogs with intracranial rare because of the patients’ short life span. meningiomas that underwent surgical resection Conventional radiotherapy consists of fracwith an ultrasonic aspirator. Surgical aspiration tionated irradiation of the tumor and a 5- to allows the surgeon to perform more complete 10-mm margin of surrounding tissue at approxtumor excision while reducing hemorrhage and imately 3 Gy per session. In dogs and cats, the iatrogenic brain damage.43 The aspirator has total dose is usually 46 to 48 Gy given over a tip that vibrates and fragments tissue while several weeks.46,47 Irradiation of canine and simultaneously providing lavage and suctioning feline brain tumors is common in veterinary matter from the surgical field. Median survival medicine, and reports in the literature describe time in this study was approximately 42 months. using radiation therapy as the sole treatment for Although ultrasonic aspiration is not yet widely intracranial masses or after subtotal resection. available in veterinary medicine, greater use of The median survival time of dogs treated with this technique may increase survival times in fractionated radiotherapy alone for extraaxial canine patients with intracranial meningiomas masses (mean total dose: 40.9 Gy) was 569 days in one study.48 Another study45 using hypofractreated with surgical removal alone.42 The aspiration study was also the first to tionated radiation (38 Gy) as the sole therapy investigate the prognostic value of tumor his- reported a mean survival time of 49.7 weeks tologic subtyping with regard to survival times. for extraaxial masses, but definitive histologic Patients with meningothelial, psammomatous, diagnosis was not obtained in each case. One or transitional meningiomas had a much bet- cat with a suprasellar meningioma diagnosed

QuickNotes Canine meningiomas tend to be friable, and almost 33% inﬁltrate the brain parenchyma.

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FIGURE 5

Dog receiving stereotactic radiosurgery with a modiﬁed LINAC system. (A) A mouth guard filled with dental compound that has been fitted to the patient’s mouth. (B) Bite plate comprising the mouth guard attached to the fiducial markers. (C) Patient with bite plate in place undergoing CT for radiosurgery planning. (D) MRI treatment plan for radiosurgery. Nas = nasal cavity.

QuickNotes Radiosurgery delivers a high dose of radiation to a welldeﬁned intracranial target in a single treatment session and is accurate to within 1 mm.

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on MRI was treated with orthovoltage radiation and lived for 240 days before dying of an unrelated neoplasm.4 Again, several studies have shown that survival times are prolonged in dogs that received radiation therapy after surgical removal of their meningiomas.9,36,41

Radiosurgery Within the past decade, stereotactic radiosurgery has gained popularity in human and veterinary medicine. Radiosurgery delivers a high dose of radiation to a well-deﬁned intracranial target in a single treatment session and is accurate to within 1 mm.11 Multiple, noncoplanar radiation beams are stereotactically focused on the tumor using an image-based planning system and a rigid head ﬁ xation device. The steep dose gradient outside the edge of the target limits the exposure of normal tissue and decreases radiation side effects. Radiosurgery can be performed with a specially adapted linear accelerator (LINAC) or

Gamma Knife (Elekta, Norcross, GA). The procedure is typically conducted on an outpatient basis. At our facility, pretreatment volumetric MRI and stereotactic CT are conducted. The CT scan is performed with a bite plate securely fastened to the pet’s teeth; the same bite plate is used to facilitate stereotactic three-dimensional localization during the actual treatment (FIGURE 5). The MRI and CT images are fused during dose planning, using an automated program that generates multiple isocenters and an optimally conformed isodense line.49 Radiosurgery has been used to irradiate brain tumors in dogs and is very attractive to pet owners because it requires only one anesthetic event. Two dogs treated in this fashion with doses of 1250 and 1000 cGy had respective survival times of 4 years and 13 months.50 This treatment option is currently available at three veterinary academic centers and one private practice in the United States. We have treated several dogs and two cats with MRI-diagnosed cerebral meningiomas using a LINAC-based stereotactic radiosurgery unit to deliver an average dose of 1500 cGy. Several patients are still doing well clinically more than 1 year posttreatment, and the case series will be published soon. Typically, we recommend radiosurgery as the primary mode of therapy for intracranial meningiomas that are relatively small (<2.5 cm in diameter) if the patient does not have severe clinical signs (i.e., normal neurologic examination with seizures as the only clinical sign) or the owner does not wish to pursue surgical excision. These treatment criteria reflect an increased risk of acute edema with larger meningiomas.51 Stereotactic radiotherapy has been shown to significantly decrease tumor volume, but this process is slow.52 Therefore, tumors that are in a surgically accessible location in animals displaying a significant mass effect and severe neurologic signs are best managed by conventional excision to quickly resolve clinical signs.

Chemotherapy Historically, chemotherapy for brain tumors has been limited by the need for drugs that can cross the blood–brain barrier. However, several medications that may have a role in treating intracranial meningioma are now available. The nitrosourea drugs carmustine and

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Intracranial Meningioma in Dogs and Cats CE lomustine are alkylating agents that are highly between dogs given hydroxyurea and those lipid soluble. They appear to act via induction that did not receive this drug as part of their of cross-linking of nucleic acid side chains in meningioma therapy. A review of six cats with DNA and are not cell-cycle specific.11 Their tentorial meningiomas reported the use of most serious adverse effect is myelosuppres- hydroxyurea (20 mg/kg/day) with no drugsion, which may interfere with treatment. While associated complications21; all cats died or these agents are not typically recommended for were euthanized because of tumor regrowth use in patients with meningiomas, one report53 during the follow-up period (6 to 30 months). described the successful use of oral lomustine to treat an intracranial meningioma in a dog. Other Therapies In this particular case, lomustine was chosen Gene therapy, brachytherapy, and immunofor treatment because the tumor type could not therapy have all been used in people for recurbe histologically confi rmed (meningioma was rent or malignant meningiomas, but their use diagnosed at necropsy). Lomustine was given is not widespread in veterinary patients. Gene every 6 weeks along with prednisolone, and the therapy consists of transferring viral DNA or RNA into a tumor to render it susceptible to patient survived for 13 months. One potentially promising treatment involves certain therapeutic agents. For example, in the antineoplastic agent hydroxyurea, which “suicide” gene therapy, a herpes simplex type is used in human and veterinary medicine for I thymidine kinase gene is transferred into long-term treatment of chronic myelogenous tumor cells, which sensitizes these cells to the leukemia and polycythemia vera. This drug antiviral drug gangcyclovir.58 An adenovirus inhibits DNA synthesis without interfering vector has been successfully transferred into with RNA or protein synthesis, and cell death a naturally occurring canine meningioma,59 occurs in the S phase of the cell cycle. Adverse but no further reports of gene therapy for this effects are minimal and include myelosuppres- indication have been published in the veterision, but this is reversible even after years of nary literature. Brachytherapy is a means of providing local therapy. Hydroxyurea was first demonstrated to radiation to a tumor via implantation of high-activarrest meningioma growth in cell culture and ity iodine-125 seeds during surgical resection. It then to cause DNA fragmentation of tumors has been used in human medicine as an adjunctransplanted into nude mice.54 Favorable tive therapy for recurrent and primary skull-base results have been achieved using hydroxyurea meningiomas but has not been described as a in human patients with meningioma,55,56 but treatment in the veterinary literature.60 Immunotherapy involves modification of the no controlled studies exist in veterinary medicine. However, the drug is often used in vet- immune system to slow the course of tumor erinary neurology as a noninvasive, relatively progression, usually by culturing and stimulatinexpensive treatment option.42 It is an oral ing autologous lymphocytes and returning them medication that can be offered to veterinary to the tumor.11,34 This mode of treatment is usupatients along with surgery and radiation in ally reserved for gliomas that do not respond cases of recurrent tumors or as an addition to to conventional therapies in humans, but it has palliative therapy. Dogs with MRI-confirmed been tried in dogs with meningiomas.61 meningiomas in which hydroxyurea was used as the sole therapy (20 mg/kg/day) had sur- Conclusion vival times of 7 to 8 months versus 3 months Surgery is the initial treatment of choice for in dogs treated with palliative therapy alone.57 intracranial meningiomas in cats and may be Two dogs that underwent ultrasonic surgical indicated in dogs. If the mass is in an accesaspiration of intracranial meningioma were sible location, surgery provides a definitive given hydroxyurea (50 mg/kg three times diagnosis and immediate resolution of mass weekly) after MRI-detected tumor recurrence effect. Cats respond well to surgical resection at 499 and 1405 days postoperatively; both of meningiomas, with a 50% survival rate at 2 dogs were still alive at the time of publica- years.7,38 Canine meningiomas are not as easily tion, with a mean survival time of 42 months.42 removed, with survival times of 7 months in No statistical difference has been established dogs treated by conventional surgery alone.40

QuickNotes Hydroxyurea is often used in veterinary neurology as a noninvasive, relatively inexpensive treatment option.

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FREE CE Intracranial Meningioma in Dogs and Cats

However, canine patients that underwent ultrasonic aspiration of meningiomas had much longer survival times (median: 3.4 years).42 Adjunctive therapy with radiation or hydroxyurea can prolong survival times in dogs.36,40,53,57 Stereotactic radiosurgery may provide equiva-

lent survival times to surgical resection in dogs and is less invasive. Ultimately, owners must be well informed about the cost, expectations, ease of therapy, and quality of life associated with each treatment option to make the best decisions for themselves and their pets.

References 1. Dewey CW. Encephalopathies: disorders of the brain. In: Dewey CW, ed. A Practical Guide to Canine and Feline Neurology. Ames: Iowa State University Press; 2003:127-136. 2. LeCouteur RA. Tumors of the nervous system. In: Withrow SJ, MacEwen EG, eds. Small Animal Clinical Oncology. Philadelphia: WB Saunders; 2001:500-531. 3. Bagley RS, Gavin PR, Moore MP, et al. Clinical signs associated with brain tumors in dogs: 97 cases (1992-1997). JAVMA 1999;215(6):818-819. 4. Troxel MT, Vite CH, Van Winkle TJ, et al. Feline intracranial neoplasia: retrospective review of 160 cases (1985-2001). J Vet Intern Med 2003;17(6):850-859. 5. McDermott MW, Quinones-Hinosa A, Fuller GN, et al. Meningiomas. In: Levin VA, ed. Cancer in the Nervous System. Oxford, UK: University Press; 2002:269-299. 6. Oakley RE, Patterson JS. Tumors of the central and peripheral nervous system. In: Slatter D, ed. Textbook of Small Animal Surgery. Philadelphia: Elsevier Science; 2003:2405-2425. 7. Gordon LE, Thacher C, Matthiesen DT, et al. Results of craniotomy for the treatment of cerebral meningioma in 42 cats. Vet Surg 1994;23(2):94-100. 8. Snyder JM, Shofer FS, Van Winkle TJ, et al. Canine intracranial primary neoplasia: 173 cases (1986-2003). J Vet Intern Med 2006;12(3):669-675. 9. Axlund TW, McGlasson ML, Smith AN. Surgery alone or in combination with radiation therapy for treatment of intracranial meningiomas in dogs: 31 cases (1989-2002). JAVMA 2002;221(11):1597-1600. 10. Tomek A, Cizinauskas S, Doher M, et al. Intracranial neoplasia in 61 cats: localisation, tumour types and seizure patterns. J Feline Med Surg 2006;8:243-253. 11. Morantz RA, Walsh JW. Brain Tumors: A Comprehensive Text. New York: Marcel Dekker; 1994. 12. Forterre F, Tomek A, Konar M, et al. Multiple meningiomas: clinical, radiological, surgical and pathological findings with outcome in four cats. J Feline Med Surg 2007;9(1):36-43. 13. Lu D, Pocknell A, Lamb CR, et al. Concurrent benign and malignant multiple meningiomas in a cat: clinical, MRI and pathological findings. Vet Rec 2003;152(25):780-782. 14. Summers BA, Cummings JF, de Lahunta A. Veterinary Neuropathology. St. Louis: Mosby-Year Book; 1995. 15. Smith TW, Folkerth RD, Poirier J, et al. Tumors of the nervous system. In: Gray F, De Girolami U, Poirier J, eds. Manual of Basic Neuropathology. Philadelphia: Butterworth-Heinemann; 2004:21-56. 16. Braund KG. Clinical Syndromes in Veterinary Neurology. St. Louis: Mosby; 1994. 17. Patnaik AK, Kay WJ, Hurvitz AI. Intracranial meningioma. a comparative pathologic study of 28 dogs. Vet Pathol 1986;23(4):369373. 18. Maeda H, Shibuya H, Suzuki K, et al. A case of anaplastic meningioma in a dog. J Vet Med Sci 2005;67(11):1177-1180. 19. Hsu DW, Efird JT, Hedley-White ET. MIB-1(Ki-67) index and transforming growth factor-alpha (TGHa) immunoreactivity are significant prognostic predictors for meningiomas. Neuropathol Appl Neurobiol 1998;24(6):441-452. 20. Sessums K, Mariani CL. Analysis of KI-67, matrix metallinoproteinase 2 and cathepsin B in canine intracranial meningiomas. J Vet Intern Med 2007;21(3):640-641. 21. Forterre F, Fritsch G, Kaiser S, et al. Surgical approach for tentorial meningiomas in cats: a review of six cases. J Feline Med Surg 2006;8:227-233. 22. Kitagawa M, Kanayama K, Sakai T. Cystic meningioma in a dog. J

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Small Anim Pract 2002;43(6):272-274. 23. Konstantinidou AE, Korkolopoulou P, Mahera H, et al. Hormone receptors in non-malignant meningiomas correlate with apoptosis, cell proliferation and recurrence-free survival. Histopathology 2003;43(3): 280-290. 24. Adamo PF, Cantile C, Steinberg H. Evaluation of progesterone and estrogen receptor expression in 15 meningiomas of dogs and cats. Am J Vet Res 2003;64(10):1310-1318. 25. Mandara MT, Ricci G, Rinaldi L, et al. Immunohistochemical identification and image analysis quantification of oestrogen and progesterone receptors in canine and feline meningioma. J Comp Pathol 2002;127(3):214-218. 26. O’Brien DP, Axlund TW. Brain disease. In: Ettinger SJ, Feldman EC, eds. Textbook of Veterinary Internal Medicine. St. Louis: Elsevier; 2005:830-833. 27. Halpin SF. Supratentorial tumours. In: Gillespie JE, Jackson A, eds. MRI and CT of the Brain. London: Arnold; 2000:122-125. 28. Troxel MT, Vite CH, Massicotte C, et al. Magnetic resonance imaging features of feline intracranial neoplasia: retrospective analysis of 46 cats. J Vet Intern Med 2004;18(2):176-189. 29. Polizopoulou ZS, Koutinas AF, Souftas VD, et al. Diagnostics correlation of CT-MRI and histopathology in 10 dogs with brain neoplasms. J Vet Med Series A 2004;51(5):226-231. 30. Bailey CS, Higgins RJ. Characteristics of cisternal cerebrospinal fluid associated with primary brain tumors in the dog: a retrospective study. JAVMA 1986;188(4):414-417. 31. Dickinson PJ, Sturges BK, Kass PH, LeCouteur RA. Characteristics of cisternal cerebrospinal fluid associated with intracranial meningiomas in dogs: 56 cases (1985-2004). JAVMA 2006;228(4): 564-567. 32. Koblik PD, LeCouteur RA, Higgins RJ, et al. CT-guided brain biopsy using a modified Pelorus mark III stereotactic system: experience with 50 dogs. Vet Radiol Ultrasound 1999;40(4):434-440. 33. Adamo PF, Forrest LF, Dubielzig R. Canine and feline meningiomas: diagnosis, treatment and prognosis. Compend Contin Educ Pract Vet 2004;27:951-966. 34. Podell, M. Seizures. In: Platt SR, Olby NJ, eds. BSAVA Manual of Canine and Feline Neurology. Gloucester, UK: Woodrow House; 2004:97-112. 35. Thomas WB. Seizures and narcolepsy. In: Dewey CW, ed. A Practical Guide to Canine and Feline Neurology. Ames: Iowa State University Press; 2003:193-212. 36. Bilderback A, Faissler D, Sato AF, et al. Transfrontal craniectomy, radiation therapy, and/or chemotherapy in the treatment of canine meningiomas [abstract]. Proc 24th ACVIM 2006. 37. Oakley RE, Patterson JS. Tumors of the central and peripheral nervous system. In: Slatter D, ed. Textbook of Small Animal Surgery. Philadelphia: Elsevier Science; 2003: 2405-2425. 38. Gallagher JG, Berg J, Knowles KE, et al. Prognosis after surgical excision of cerebral meningioma in cats: 17 cases (1986-1992). JAVMA 1993;203(10):1437-1440. 39. Bagley RS. Fundamentals of Veterinary Clinical Neurology. Ames, Iowa: Blackwell Publishing; 2005. 40. Niebauer GW, Dayrell-Hart BL, Speciale J. Evaluation of craniotomy in dogs and cats. JAVMA 1991;198(1):89-95. 41. Theon AP, LeCouteur RA, Carr EA, Griffey SM. Influence of tumor cell proliferation and sex-hormone receptors on effectiveness of radiation therapy for dogs with incompletely resected meningiomas. JAVMA 2000;216(5):701-707. 42. Greco JJ, Aiken SA, Berg JM, et al. Evaluation of intracranial meningioma resection with a surgical aspirator in dogs: 17 cases (1996-

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Intracranial Meningioma in Dogs and Cats CE 2004). JAVMA 2006;229(3):394-400. 43. Berg JM. Canine meningiomas, other approaches: hydroxyurea and ultrasonic aspiration. Proc 23rd ACVIM 2004. 44. Bagley RS. Coma, stupor and behavioural change. In: Platt SR, Olby NJ, eds. BSAVA Manual of Canine and Feline Neurology. Gloucester, UK: BSAVA; 2004:126-128. 45. Brearley MJ, Jeffery ND, Phillips SM, Dennis R. Hypofractionated radiation therapy of brain masses in dogs: a retrospective analysis of survival of 83 cases (1991-1996). J Vet Intern Med 1999;13:408412. 46. Heidner GL, Kornegay JN, Page RL, et al. Analysis of survival in a retrospective study of 86 dogs with brain tumors. J Vet Intern Med 1991;(5)4:219-226. 47. Spugnini EP, Thrall DE, Price GS, et al. Primary irradiation of canine intracranial masses. Vet Radiol Ultrasound 2000;41(4):377-380. 48. Bley CR, Sumova A, Roos M, et al. Irradiation of brain tumors in dogs with neurologic disease. J Vet Intern Med 2005;19:849-854. 49. Friedman WA, Foote KD. Linear accelerator-based radiosurgery for vestibular schwannoma. Neurosurg Focus 2003;14(5):1-8. 50. Lester NV, Hopkins AL, Bova FJ, et al. Radiosurgery using a stereotactic headframe system for irradiation of brain tumors in dogs. JAVMA 2001;219(11):1562-1567. 51. Kollova A, Lisca KR, Novotna J, et al. Gamma knife surgery for benign meningioma. J Neurosurg 2007;107(2):325-336. 52. Henzel M, Gross MW, Hamm K, et al. Signiﬁcant tumor volume reduction of meningiomas after stereotactic radiotherapy: results of a prospective multicenter study. Neurosurgery 2006;59(6):1188-1194.

53. Jung DI, Kim HJ, Park C, et al. Long-term chemotherapy with lomustine of intracranial meningioma occurring in a miniature Schnauzer. J Vet Med Sci 2006;68(4):383-386. 54. Schrell UM, Rittig MG, Anders M, et al. Hydroxyurea for treatment of unresectable and recurrent meningiomas. I. Inhibition of primary human meningioma cells in culture and in meningioma transplants by induction of the apoptotic pathway. J Neurosurg 1997;86(5):845852. 55. Schrell UM, Rittig MG, Anders M, et al. Hydroxyurea for treatment of unresectable and recurrent meningiomas. II. Decrease in the size of meningiomas in patients treated with hydroxyurea. J Neurosurg 1997;86(5):840-844. 56. Hahn BM, Schrell UM, Sauer R, et al. Prolonged oral hydroxyurea and concurrent 3D-conformal radiation in patients with progressive or recurrent meningioma: results of a pilot study. J Neurooncol 2005;74(2):157-165. 57. Dewey CW. Hydroxyurea and meningiomas. Veterinary Information Network. Accessed February 2009 at www.vin.com. 58. Alekhteyar KM, Glatstein E. Radiotherapy management of brain tumors. In: Kornblith PL, Walker MD, eds. Advances in Neuro-Oncology II. New York: Futura; 1997:316-317. 59. Chauvet AE, Kesava PP, Goh CS, et al. Selective intraarterial gene delivery into a canine meningioma. J Neurosurg 1998;88:870-873. 60. Kumar PP, Patil AA, Syh HW, et al. Role of brachytherapy in the management of the skull base meningioma. Cancer 1993;71:3726-3731. 61. Ingram M, Jacques D, Freshwater D, et al. Adoptive immunotherapy of brain tumors in dogs. Vet Med Rep 1990;2:398-402.

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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 is the most common clinical sign of an intracranial meningioma in dogs? a. tetraparesis b. seizures c. extreme lethargy d. blindness

5. Lower progesterone expression in canine and feline meningiomas correlates with a. early recurrence. b. a lower recurrence risk. c. the presence of a secondary tumor. d. none of the above

2. Which statement is false with regard to most meningiomas in cats? a. They are extraaxial. b. They arise from the arachnoid space. c. They are invasive to normal brain tissue. d. They are ﬁrm.

6. Surgery for meningiomas in dogs a. can be difﬁcult due to the invasive nature of the tumor. b. is not recommended. c. is as effective as surgery in cats. d. is only performed with a surgical aspirator.

3. The nuclear protein Ki-67 is used a. as a proliferation marker for brain tumors. b. to determine the likelihood of recurrence and prognosis for meningiomas. c. to determine the WHO tumor grade. d. all of the above

7. Late effects of radiation are a. common in veterinary patients. b. due to vasogenic brain edema. c. irreversible. d. seen within days of treatment.

4. Which grade of meningioma is associated with the highest Ki-67 levels? a. I b. II c. III d. IV

8. Which statement is false with regard to radiosurgery? a. It requires only one treatment session. b. It is used for malignant meningiomas in dogs. c. It is recommended for veterinary

patients with severe neurologic signs. d. It can be used for skull-based meningiomas. 9. Which drug has been used to treat canine intracranial meningiomas with promising results? a. hydroxyurea b. tamoxifen c. mifepristone d. vincristine 10. Which postsurgical treatment option confers the greatest improvement in survival times in dogs? a. chemotherapy b. a second surgical procedure c. radiation d. immunotherapy

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Pathogen Test Antech Diagnostics has released a new molecular diagnostic test for the ﬁve most common causes of feline upper respiratory disease. The FastPanel PCR Feline Upper Respiratory Proﬁle tests a single sample for feline calicivirus, feline herpesvirus-1, Bordetella bronchiseptica, Chlamydophila felis, and Mycoplasma felis. Test results are available in 1 to 3 days. Antech Diagnostics | 800-872-1001 | www.antechdiagnostics.com

Imaging ImageV PACS is a picture archiving and communication system designed for veterinary use. It allows viewing of conventional and digital radiographs, as well as CCD, ultranographic, endoscopic, and digital dental images. The device integrates with other AFP offerings. ImageV PACS is available alone or with the Konica Regius Model 110 CR. AFP Imaging Corporation | 800-592-6666 | www.afpimaging.com

Ultrasound Aloka has enhanced the ProSound Alpha 7 ultrasonography console. The device has an ergonomic design with a height-adjustable console, is the smallest, lightest system in its class, and consumes 40% less electricity than previous models. The ProSound has extensive storage capabilities, including USB and DVD storage. Aloka Company Ltd. 800-872-5652 | www.aloka.com

Computer Peripherals The CleanKey keyboard and mouse are designed to be durable and waterproof for better infection control, hygiene, and ruggedness. Both devices are fully waterproof, even when completely submerged in liquid, and have a “clean key,” which stops data being sent to the computer, allowing cleaning at the point of use. Devlin Keyboards | +44 (0) 1256 467367 | devlin.co.uk

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

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INDICATION vetsulin® (porcine insulin zinc suspension) is indicated for the reduction of hyperglycemia and hyperglycemiaassociated clinical signs in dogs and cats with diabetes mellitus. CONTRAINDICATIONS Dogs and cats known to have a systemic allergy to pork or pork products should not be treated with vetsulin®. vetsulin® is contraindicated during periods of hypoglycemia. WARNINGS User Safety: For use in animals only. Keep out of the reach of children. Avoid contact with eyes. In case of contact, immediately flush eyes with copious amounts of water for 15 minutes. Accidental injection may cause clinical hypoglycemia. In case of accidental injection, seek medical attention immediately. Exposure to product may induce a local or systemic allergic reaction in sensitized individuals. Animal Safety: Owners should be advised to observe for signs of hypoglycemia (see Owner Information Sheet). Use of this product, even at established doses, has been associated with hypoglycemia. An animal with signs of hypoglycemia should be treated immediately. Glucose should be given orally or intravenously as dictated by clinical signs. Insulin should be temporarily withheld and, subsequently, the dosage should be adjusted, if indicated. Any change in insulin should be made cautiously and only under a veterinarian’s supervision. Changes in insulin strength, manufacturer, type, species (animal, human) or method of manufacture (rDNA versus animal-source insulin) may result in the need for a change in dosage. Appropriate diagnostic tests should be performed to rule out endocrinopathies in pets that are difficult to regulate (e.g., hyperadrenocorticism in dogs and hyperthyroidism in cats). PRECAUTIONS Animals presenting with severe ketoacidosis, anorexia, lethargy, and/or vomiting should be stabilized with short-acting insulin and appropriate supportive therapy until their condition is stabilized. As with all insulin products, careful patient monitoring for hypoglycemia and hyperglycemia are essential to attain and maintain adequate glycemic control and prevent associated complications. Overdosage can result in profound hypoglycemia and death. Progestogens, certain endocrinopathies, and glucocorticoids can have an antagonistic effect on insulin activity. Intact bitches should be ovariohysterectomized. Progestogen and glucocorticoid use should be avoided. Drug Interactions: In the US clinical effectiveness studies, dogs and cats received various medications while being treated with vetsulin® including antimicrobials, antivirals, antifungals, antihistamines, analgesics, anesthetics/tranquilizers, diuretics, bronchodilators, corticosteroids (cats), NSAIDs, thyroid hormone supplementation, hyperthyroid medication (methimazole), internal and external parasiticides, anti-emetics, dermatological topical treatments and oral supplements, ophthalmic preparations containing antimicrobials and antiinflammatories, and various vaccines. No medication interactions were reported. This drug was not studied in dogs receiving corticosteroids. Reproductive Safety: The safety and effectiveness of vetsulin® in breeding, pregnant, and lactating dogs and cats has not been evaluated. Use in puppies and kittens: The safety and effectiveness of vetsulin® in puppies and kittens has not been evaluated. ADVERSE REACTIONS

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 e-mail chobbs@vetlearn.com.

It’s not just therapeutics!

Dogs In the field effectiveness and safety study, 66 dogs were treated with vetsulin®. Sixty-two dogs were included in the assessment of safety. Hypoglycemia (defined as blood glucose <50 mg/dL) with or without associated clinical signs occurred in 35.5% (22/62) of the dogs at various times during the study. Clinical signs of hypoglycemia were generally mild in nature (described as weakness, lethargy, stumbling, falling down, and/or depression). Disorientation and collapse were reported less frequently and occurred in 16.1% (10/62) of the dogs. Two dogs had a seizure and one dog died during the seizure. Although never confirmed, the presumptive diagnosis was hypoglycemia-induced seizures. In the rest of the dogs, hypoglycemia resolved with appropriate therapy and adjustments in insulin dosage. Seven owners recorded the following observations about the injection site on the home monitoring forms: swollen, painful, sore, and a bleb under the skin. The following clinical observations occurred in the field study following treatment with vetsulin® and may be directly attributed to the drug or may be secondary to the diabetic state or other underlying conditions in the dogs: hematuria, vomiting, diarrhea, pancreatitis, non-specific hepatopathy/pancreatitis, development of cataracts, and urinary tract infections. Cats In a field effectiveness and safety study, safety data was reported for 78 cats receiving vetsulin®. Hypoglycemia (defined as blood glucose <50 mg/dL) was reported in 61 cats (88 total incidences). Fifteen of the occurrences (involving 13 cats) were associated with clinical signs described as lethargy, diarrhea, decreased appetite/anorexia, vomiting, and hypothermia. One cat had seizures following accidental overdosing by the owner and again during the subsequent dose adjustment period. The cat responded to supportive therapy and had no further hypoglycemic episodes. In all cases of hypoglycemia, the clinical signs resolved following symptomatic treatment and/or dose adjustment. Polyneuropathy was reported in 4 cats. Two injection site reactions were reported: one as a mildly thickened subcutaneous tissue reaction and the second as a mild bruising. The following clinical observations occurred in the field study following treatment with vetsulin® and may be directly attributed to the drug or may be secondary to the diabetic state or other underlying conditions in the cats: vomiting, lethargy, diarrhea, decreased appetite/anorexia, pancreatitis, dermal events, respiratory disease, urinary tract disorder, renal disease, dehydration, weight loss, polydipsia, polyuria, behavioral change, and ocular discharge/conjunctivitis. In a smaller field effectiveness and safety study, 14 cats were treated with vetsulin®. Hypoglycemia was reported in 6 cats (8 total occurrences). Lethargy not associated with hypoglycemia was reported in 4 cats (6 total occurrences). The following clinical observations occurred in the field study following treatment with vetsulin® and may be directly attributed to the drug or may be secondary to the diabetic state or other underlying conditions in the cats: foul odor to stool, diarrhea, dull coat, rapid, shallow breathing, stiff gate in rear, gallop rhythm, and pruritus with alopecia. During the 1998-2007 period, the following adverse events in 50 cats treated with porcine insulin zinc suspension were reported to Intervet International and Intervet Inc.: Death, seizures, lack of effectiveness/dysregulation, hypoglycemia, allergic or skin reaction, lethargy, vomiting/diarrhea, injection pain, hyperthermia, nystagmus, PU/PD, and abnormal behavior. To report adverse reactions, call 1-800-345-4735. Additional information about vetsulin® and diabetes mellitus can be found at www.vetsulin.com Distributed by: INTERVET INC. Millsboro, DE 19966 Made in Germany 01/08 Vetsulin is the property of Intervet International B.V. or affiliated companies or licensors and is protected by copyrights, trademark and other intellectual property laws. Copyright © 2009 Intervet International B.V. All rights reserved. CA-VETPI-9276CH6/09 Intervet/Schering-Plough Animal Health 56 Livingston Avenue Roseland, New Jersey 07068 USA Phone: 800 521 5767 www.intervetusa.com

Abstract Thoughts CONTINUED FROM PAGE 329

modiﬁed inside-to-outside technique, which has the advantages of speed, simplicity, and absence of the need to suture catheters, was used for cystotomy. Catheterization lasted 5 to 14 days; stricture occurred in three cats. Postoperative complications involved inadvertent removal of catheters and urine leakage. Maintenance of a closed urine collection system was problematic. (The authors recommend intermittent drainage of a closed catheter.) The outcome was good, with urethral healing, in eight of 10 cats. Strictures can form, but the risk seemed low. Based on this study, urethral catheterization is simpler and less invasive than primary repair or urethrostomy for urethral injuries. This procedure was better than retrograde urethrography for diagnosing partial urethral disruption. Because of the risk of infection with antibiotic-resistant bacteria, cats with indwelling urinary catheters should not be given antibacterial drugs. The suggested maximum duration of catheterization is 7 days, although further studies should conﬁrm this time period.

Skeletal Histiocytic Sarcoma in Dogs Schultz RM, Puchalski SM, Kent M, Moore PF. Skeletal lesions of histiocytic sarcoma in 19 dogs. Vet Radiol Ultrasound 2007;48:539-543.

Localized and disseminated histiocytic sarcoma may differ with regard to outcome, which would make early diagnosis and differentiation impor-

tant. This retrospective study evaluated clinical and radiographic findings from the medical records of 19 dogs with diagnosed histiocytic sarcoma bone lesions. Signalment, history, physical examination fi ndings, laboratory test results, and radiographic, biopsy, and necropsy findings, including soft tissue masses and spinal cord compression, were analyzed. The dogs were divided into two groups: localized disease (four dogs) and disseminated disease (15 dogs). The groups had similar historical, clinical, and laboratory findings: age, breeds affected, and the presence of lameness, aggressive bone lesions (periarticular bones, vertebrae, humerus, and rib), lymph node enlargement, bone lysis, and soft tissue masses. The skeletal sites were similar. Golden retrievers and rottweilers older than 5 years with lameness or neurologic deficits localized to the spinal cord were most commonly represented. All the rottweilers in the study had disseminated disease. Localized and disseminated disease could not be differentiated according to historical, clinical, and laboratory findings, but differentiation was possible using imaging and histologic results. Histiocytic sarcoma should be considered as a diagnostic differential in middle-aged to older golden retrievers and rottweilers with lameness or neurologic deficits and aggressive bone lesions on radiographs, especially those with a soft tissue mass.

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Compendium... and so much more! 344

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

Month-long flea protection in a chewable tablet

Fast-acting

Convenient

Family-friendly

• Starts killing fleas in 30 minutes • 100% effective within 4 hours in a controlled laboratory study • Approved by the FDA and available by prescription only To learn more about Comfortis®, see your Elanco/Lilly representative or distributor representative, call 1 (888) 545-5973 or visit www.comfortis4dogs.com The most common adverse reaction recorded during clinical trials was vomiting. Other adverse reactions were decreased appetite, lethargy or decreased activity, diarrhea, cough, increased thirst, vocalization, increased appetite, redness of the skin, hyperactivity and excessive salivation. For product label, including important safety information, see page 344. ©2009 Elanco CF00417 070109

Doesn’t wash off

NOW FDA-APPROVED FOR CATS!

In feline diabetes

The right balance of proven performance and unparalleled support is only available from one insulin. Vetsulin® (porcine insulin zinc suspension). 15+ years of successful use globally plus a comprehensive portfolio of support tools. Vetsulin is the best place to start when it comes to cats with newly diagnosed diabetes. You want a therapy proven to work in this challenging disease. With a long track record internationally,* Vetsulin now provides veterinarians in the US with a reliable new therapy option. In addition to proven performance, Vetsulin comes with a whole host of support materials and service simply unavailable with any other insulin product. Vetsulin. Striking the right balance in feline diabetes care. www.vetsulin.com

DIABETES VETSUPPORT: 877.783.4840

See accompanying Prescribing Information for side effects, warnings, and contraindications. * Vetsulin is known as Caninsulin® in Canada, Europe, and Australia. Caninsulin and Vetsulin are the property of Intervet International B.V. or affiliated companies or licensors and are protected by copyrights, trademark and other intellectual property laws. Copyright © 2009 Intervet International B.V. All rights reserved. CA-VET-9276CH6/09 Intervet/Schering-Plough Animal Health 56 Livingston Avenue • Rosedale, New Jersey 07068 • USA Phone: 800 521 5767 • www.intervetusa.com

See Page 343 for Product Information Summary