ONCOLOGY DOXORUBICIN: USES AND PRECAUTIONS
PARASITOLOGY FELINE HEARTWORM DISEASE
TOXICOLOGY TRAZODONE EXPOSURE
ANTIMICROBIALS FOLLOWING THE GUIDELINES
PERSONAL WELLNESS THE TRUTH ABOUT BULLYING
TODAY’SVETERINARYTECHNICIAN | An Official Journal of the NAVC | todaysveterinarytechnician.com | Volume 2, Number 3 | May/June 2017 |
Successful CPR: TEAM PREPARATION AND THE RECOVER GUIDELINES
YOU’VE GOT HER BACK. VETMEDIN® HAS HER HEART.
No other canine CHF drug offers the same level of research and support as Boehringer Ingelheim Vetmedica, Inc. Industry-trusted VETMEDIN gives dogs with congestive heart failure (CHF) better days and longer lives.1 It’s backed by years of groundbreaking canine cardiology research. And only VETMEDIN offers free tools that educate your clients to recognize the signs of CHF faster—which can lead to treatment sooner. Contact your Boehringer Ingelheim Vetmedica, Inc. representative today for a heart to heart about VETMEDIN. Reference: 1. Lombard CW, Jöns O, Bussadori CM; for the VetSCOPE Study. Clinical efficacy of pimobendan versus benazepril for the treatment of acquired atrioventricular valvular disease in dogs. J Am Anim Hosp Assoc. 2006;42(4):249–261.
IMPORTANT SAFETY INFORMATION: Use only in dogs with clinical evidence of heart failure. The safety of VETMEDIN has not been established in dogs with asymptomatic heart disease or in heart failure caused by etiologies other than atrioventricular valvular insufficiency or dilated cardiomyopathy. Please refer to the package insert for complete product information or visit www.vetmedin.com. VETMEDIN is a registered trademark of Boehringer Ingelheim Vetmedica GmbH, licensed to Boehringer Ingelheim Vetmedica, Inc. © 2016 Boehringer Ingelheim Vetmedica, Inc. VET0515009
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TODAY’SVETERINARYTECHNICIAN todaysveterinarytechnician.com
MAY/JUNE 2017
Editor in Chief Lynne Johnson-Harris, LVT, RVT LJohnson@NAVC.com
Editorial Advisory Board Brenda K. Feller, LVT, CVT, VTS (Anesthesia) Animal Specialty Hospital of Florida, Naples, Florida Rosemary Lombardi, CVT, VTS (Emergency and Critical Care) Director of Nursing, University of Pennsylvania Matthew J. Ryan Veterinary Hospital Jeanne R. Perrone, CVT, VTS (Dentistry) VT Dental Training, Plant City, Florida Heidi Reuss-Lamky, LVT, VTS (Anesthesia and Analgesia, Surgery) Oakland Veterinary Referral Services, Bloomfield Hills, Michigan Kathi L. Smith, RVT, VTS (Oncology) Portland Veterinary Specialists Portland, Maine Deborah A. Stone, MBA, PhD, CVPM StoneVPM Austin, Texas Daniel J. Walsh, MPS, RVT, LVT, VTS (Clinical Pathology) Purdue University (Retired)
Ann Wortinger, BIS, LVT, VTS (ECC, SAIM, Nutrition) 4 Cats Consulting Belleville, Michigan
CONTACT US
An Official Journal of the NAVC
VOLUME 2, NUMBER 3
Chief Executive Officer Thomas M. Bohn, MBA, CAE
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TODAY’SVETERINARYTECHNICIAN
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090340591/0 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, 5 or 10 mg pimobendan per tablet. Pimobendan, a benzimidazole-pyridazinone derivative, is a non-sympathomimetic, 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)-1H-benzimidazole5-yl]-5-methyl-3(2H)-pyridazinone. The structural formula of pimobendan is:
Indications: Vetmedin (pimobendan) is indicated for the management of the signs of mild, moderate, or severe (modified NYHA Class IIa, IIIb, or IVc) 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
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.
b
A dog with modified NYHA Class III heart failure is comfortable at rest, but exercise capacity is minimal.
c
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
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 Adverse reactions/new clinical findings were seen in drug accumulation (increased positive inotropic effect). both treatment groups and were potentially related to CHF, the therapy of CHF, or both. The following adverse Laboratory studies indicate that the positive inotropic effect of pimobendan may be attenuated by the reactions/new clinical findings are listed according to concurrent use of a β-adrenergic blocker or a calcium body system and are not in order of prevalence: CHF channel blocker. death, sudden death, chordae tendineae rupture, left atrial tear, arrhythmias overall, tachycardia, syncope, Effectiveness: In a double-masked, multi-site, 56-day weak pulses, irregular pulses, increased pulmonary field study, 355 dogs with modified NYHA Class II, III, or edema, dyspnea, increased respiratory rate, coughing, IV CHF due to AVVI or DCM were randomly assigned gagging, pleural effusion, ascites, hepatic congestion, to either the active control (enalapril maleate) or the decreased appetite, vomiting, diarrhea, melena, weight Vetmedin (pimobendan) treatment group. Of the 355 loss, lethargy, depression, weakness, collapse, shaking, dogs, 52% were male and 48% were female; 72% were trembling, ataxia, seizures, restlessness, agitation, diagnosed with AVVI and 28% were diagnosed with pruritus, increased water consumption, increased DCM; 34% had Class II, 47% had Class III, and 19% urination, urinary accidents, azotemia, dehydration, had Class IV CHF. Dogs ranged in age and weight abnormal serum electrolyte, protein, and glucose from 1 to 17 years and 3.3 to 191 lb, respectively. The values, mild increases in serum hepatic enzyme levels, most common breeds were mixed breed, Doberman and mildly decreased platelet counts. Pinscher, Cocker Spaniel, Miniature/Toy Poodle, See Table 1 for mortality due to CHF (including Maltese, Chihuahua, Miniature Schnauzer, Dachshund, euthanasia, natural death, and sudden death) and for and Cavalier King Charles Spaniel. The 180 dogs (130 the development of new arrhythmias (not present in a AVVI, 50 DCM) in the active control group received dog prior to beginning study treatments) by treatment enalapril maleate (0.5 mg/kg once or twice daily), and group and type of heart disease (AVVI or DCM) in the all but 2 received furosemide. Per protocol, all dogs 56-day field study. with DCM in the active control group received digoxin. The 175 dogs (126 AVVI, 49 DCM) in the Vetmedin Table 1: CHF Death and New Arrhythmias group received pimobendan (0.5 mg/kg/day divided in the 56-Day Field Study into 2 portions that were not necessarily equal, and the ® Vetmedin Active Control portions were administered approximately 12 hours Group Group apart), and all but 4 received furosemide. Digoxin was Dogs that 14.3% 14.4% optional for treating supraventricular tachyarrhythmia died n = 175 n = 180 in either treatment group, as was the addition of a due to CHF β-adrenergic blocker if digoxin was ineffective in 9 of 126 dogs 16 of 130 dogs controlling heart rate. After initial treatment at the clinic with AVVI with AVVI on Day 1, dog owners were to administer the assigned 16 of 49 dogs 10 of 50 dogs product and concurrent medications for up to 56±4 days. with DCM with DCM The determination of effectiveness (treatment success) Dogs that 39.4% 45.0% for each case was based on improvement in at developed n = 175 n = 180 least 2 of the 3 following primary variables: modified new a 45 of 126 dogs 59 of 130 dogs NYHA classification, pulmonary edema score by a arrhythmias with AVVI with AVVI masked veterinary radiologist, and the investigator’s overall clinical effectiveness score (based on physical 24 of 49 dogs 22 of 50 dogs examination, radiography, electrocardiography, and with DCM with DCM clinical pathology). Attitude, pleural effusion, coughing, a New arrhythmias included supraventricular premature activity level, furosemide dosage change, cardiac beats and tachycardia, atrial fibrillation, atrioventricular size, body weight, survival, and owner observations were secondary evaluations contributing information block, sinus bradycardia, ventricular premature beats supportive to product effectiveness and safety. and tachycardia, and bundle branch block Based on protocol compliance and individual case Following the 56-day masked field study, 137 dogs integrity, 265 cases (134 Vetmedin, 131 active control) in the Vetmedin group were allowed to continue on were evaluated for treatment success on Day 29. See Vetmedin in an open-label extended-use study without Table 2 for effectiveness results. restrictions on concurrent therapy. The adverse reactions/new clinical findings in the extended-use Table 2: Effectiveness Results study were consistent with those reported in the 56-day for the 56-Day Field Study study, with the following exception: One dog in the Vetmedin® Active Control extended-use study developed acute cholestatic liver Group Group failure after 140 days on Vetmedin and furosemide. Treatment 80.7% 76.3% In foreign post-approval drug experience reporting, the Success on n=134 n=131 following additional suspected adverse reactions were Day 29 88 of 101 dogs 77 of 100 dogs reported in dogs treated with a capsule formulation with AVVI with AVVI of pimobendan: hemorrhage, petechia, anemia, hyperactivity, excited behavior, erythema, rash, 20 of 33 dogs 23 of 31 dogs drooling, constipation, and diabetes mellitus. with DCM with DCM To report suspected adverse reactions, to obtain a Treatment 71.1% 67.2% Material Safety Data Sheet, or for technical assistance Success on n=113 n=110 call 1-866-638-2226. Day 56 66 of 85 dogs 56 of 85 dogs Clinical Pharmacology: Pimobendan is oxidatively with AVVI with AVVI demethylated to a pharmacologically active metabolite 13 of 28 dogs 17 of 25 dogs which is then conjugated with sulfate or glucuronic with DCM with DCM acid and excreted mainly via feces. The mean extent of protein binding of pimobendan and the active No increase metabolite in dog plasma is >90%. Following a single in furosemide 78.3% 68.6% oral administration of 0.25 mg/kg Vetmedin tablets dose between n=130 n=126 the maximal mean (± 1 SD) plasma concentrations Day 1 and (Cmax) of pimobendan and the active metabolite were Day 29 3.09 (0.76) ng/ml and 3.66 (1.21) ng/ml, respectively. Individual dog Cmax values for pimobendan and the At the end of the 56-day study, dogs in the Vetmedin active metabolite were observed 1 to 4 hours postgroup were enrolled in an unmasked field study to dose (mean: 2 and 3 hours, respectively). The total monitor safety under extended use, without restrictions body clearance of pimobendan was approximately on concurrent medications. 90 mL/min/kg, and the terminal elimination half-lives Vetmedin was used safely in dogs concurrently of pimobendan and the active metabolite were receiving furosemide, digoxin, enalapril, atenolol, approximately 0.5 hours and 2 hours, respectively. spironolactone, nitroglycerin, hydralazine, diltiazem, Plasma levels of pimobendan and active metabolite antiparasitic products (including heartworm were below quantifiable levels by 4 and 8 hours after prevention), antibiotics (metronidazole, cephalexin, oral administration, respectively. The steady-state amoxicillin-clavulanate, fluoroquinolones), topical volume of distribution of pimobendan is 2.6 L/kg ophthalmic and otic products, famotidine, theophylline, indicating that the drug is readily distributed into levothyroxine sodium, diphenhydramine, hydrocodone, tissues. Food decreased the bioavailability of an aqueous solution of pimobendan, but the effect of food metoclopramide, and butorphanol, and in dogs on on the absorption of pimobendan from Vetmedin tablets sodium-restricted diets. is unknown. Palatability: In a laboratory study, the palatability of Vetmedin was evaluated in 20 adult female Beagle In normal dogs instrumented with left ventricular (LV) dogs offered doses twice daily for 14 days. Ninety pressure transducers, pimobendan increased LV dP/ percent (18 of 20 dogs) voluntarily consumed more dtmax (a measure of contractility of the heart) in a than 70% of the 28 tablets offered. Including two dogs dose dependent manner between 0.1 and 0.5 mg/ that consumed only 4 and 7% of the tablets offered, the kg orally. The effect was still present 8 hours after average voluntary consumption was 84.2%. dosing. There was a delay between peak blood levels
(7%), sudden death (6%), ascites (6%), and heart murmur (3%). Prevalence was similar in the active control group. The prevalence of renal failure was higher in the active control group (4%) compared to the Vetmedin group (1%).
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. Table 3: Incidence of Cardiac Pathology/ Histopathology in the Six-month Safety Study 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
a
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 non-escape 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 20° to 25°C (68° to 77°F), excursions permitted between 15° and 30°C (between 59° and 86°F). How Supplied: Vetmedin® (pimobendan) Chewable Tablets: Available as 1.25, 2.5, 5 and 10 mg oblong half-scored chewable tablets - 50 tablets per bottle. NDC 0010-4480-01-1.25 mg - 50 tablets NDC 0010-4481-01-2.5 mg - 50 tablets NDC 0010-4482-01-5 mg - 50 tablets NDC 0010-4479-01-10 mg - 50 tablets Manufactured by: Boehringer Ingelheim Promeco S.A. de C.V. Mexico City, Mexico Manufactured for: Boehringer Ingelheim Vetmedica, Inc. St. Joseph, MO 64506 U.S.A. Vetmedin® is a registered trademark of Boehringer Ingelheim Vetmedica GmbH licensed to Boehringer Ingelheim Vetmedica, Inc. Copyright © 2013 Boehringer Ingelheim Vetmedica, Inc. or an affiliated company. All Rights Reserved. 448005-00 Revised 06/2013
CONTENTS
TODAY’SVETERINARYTECHNICIAN An Official Journal of the NAVC
todaysveterinarytechnician.com
MAYJUNE2017
Volume 2, Number 3
PEER-REVIEWED CE Critical Components of Successful CPR: The RECOVER Guidelines, Preparedness, and Team KENICHIRO YAGI, BS, RVT, VTS (ECC, SAIM)
Less than 6% of dogs and cats that experience cardiopulmonary arrest survive to discharge. The veterinary team needs to be well trained in cardiopulmonary resuscitation and be ready to deliver it. Key aspects include preparedness and prevention, basic and advanced life support, monitoring, and postarrest care. To see the CE test for this article, please visit todaysveterinarytechnician.com.
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Doxorubicin: An Overview EMILY FULLERTON, RVT, VTS (ONCOLOGY)
Doxorubicin is one of the most dangerous chemotherapeutics used in veterinary oncology. However, it is also one of the most common and efficacious treatments for several types of canine and feline cancer. This article provides an overview of doxorubicin’s uses and precautions to take when administering it. To see the CE test for this article, please visit todaysveterinarytechnician.com.
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FEATURE Feline Heartworm Disease: Fact or Fiction? ANN WORTINGER, BIS, LVT, VTS (ECC, SAIM, NUTRITION)
In areas where dogs are exposed to mosquitoes that carry Dirofilaria immitis, so are cats. Feline heartworm disease differs from canine disease in many ways, making it important for veterinary technicians to be aware of the risks and clinical signs in cats.
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ON THE COVER (Left to right) Walter Brown, RVT, Damion Asselin, RVT, and De Anna Bedard, RVT, demonstrate proper cardiopulmonary resuscitation technique at the University of Georgia. Photo: Christopher B. Herron. ©2017 University of Georgia.
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CONTENTS
TODAY’SVETERINARYTECHNICIAN An Official Journal of the NAVC
todaysveterinarytechnician.com
MAYJUNE2017
Volume 2, Number 3
COLUMNS Editor’s Letter | The Volunteer Spirit
LYNNE JOHNSON-HARRIS, LVT, RVT. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6
Toxicology Talk | Trazodone in Veterinary Medicine TAMARA FOSS, CVT. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
VET Report Vitals | How Often Does Treatment Follow the Guidelines? RACHEL BECK, CVT, PMP and NATHANIEL SPOFFORD, MPH. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
What Moves You? | Stories of Resilience DEBORAH A. STONE, MBA, PHD, CVPM.. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Final Thoughts | Bully Tactics JULIE SQUIRES, CCFS. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
50
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CLIENT HANDOUTS Heartworm Disease in Cats................... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 46
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Careers | Employment Opportunities.. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 61 Dr. Earl H. Rippie Scholarship.. ........ . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 61 Advertiser Index......................................... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 61
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Today’s Veterinary Technician (ISSN 2472-209X print and ISSN 2472-2103 online) does not, by publication of ads, express endorsement or verify the accuracy and effectiveness of the products and claims contained therein. The publisher, Eastern States Veterinary Association, Inc (NAVC), disclaims any liability for any damages resulting from the use of any product advertised herein and suggests that readers fully investigate the products and claims prior to purchasing. The opinions stated in this publication are those of the respective authors and do not necessarily represent the opinions of the NAVC nor its Editorial Advisory Board. NAVC does not guarantee nor make any other representation that the material contained in articles herein is valid, reliable, or accurate; nor does the NAVC assume any responsibility for injury or death arising from any use, or misuse, of same. There is no implication that the material published herein represents the best or only procedure for a particular condition. It is the responsibility of the reader to verify the accuracy and applicability of any information presented and to adapt as new data becomes publicly available. Today’s Veterinary Technician (ISSN 2472-209X; print version) is published bi-monthly (Jan/Feb, Mar/Apr, May/June, Jul/Aug, Sept/Oct, Nov/Dec; 6x per year) by NAVC, 37 Paul Lane, Glen Mills, PA 19342. Application to Mail at Periodicals Postage Prices is Pending at Glen Mills, PA 19342 and additional mailing offices. POSTMASTER: Send all UAA to CFS (See DMM 507.1.5.2); NON-POSTAL AND MILITARY FACILITIES: send address corrections to CDS/Today’s Veterinary Technician, 440 Quadrangle Drive, Ste E, Bolingbrook, IL 60440.
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®
®
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Epilepsy can make your clients feel powerless – but now, you can offer them an additional way to help their dogs. Purina® Pro Plan® Veterinary Diets NeuroCare is formulated with medium chain triglyceride oil to help nutritionally manage dogs with epilepsy along with their current medication. Give your clients the power of nutrition to help their dogs in a new way, every day.
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TO L E A R N M O R E A B O U T N E U RO CA R E , V I S I T PURINAPROPLANVETS.COM. Law TH, Davies ES, Pan Y, et al. A randomised trial of a medium-chain TAG diet as treatment for dogs with idiopathic epilepsy. Br J Nutr. 2015 Nov 14;114(9):1438-47 Purina trademarks are owned by Société des Produits Nestlé S.A. Printed in USA.
*as an adjunct to veterinary therapy
The Volunteer Spirit
EDITOR’S LETTER
The Volunteer Spirit
EDITOR’S LETTER
Lynne Johnson-Harris, LVT, RVT | Editor in Chief
What is volunteerism? One definition is the principle of donating time and energy for the benefit of other people in the community as a social responsibility rather than for any financial reward. Another is the policy or practice of volunteering one’s time or talents for charitable, educational, or other worthwhile activities.1 For the past 15 years, my husband has volunteered to work on the construction crew at the Ironman Triathlon World Championship. I’ve now been involved for several years. This past April, we decided to add another event to our schedule, so we joined the volunteer construction crew for the Lavaman Triathlon on the Big Island of Hawaii. Working VOLUNTEERS offer encouragement to construction, we athletes at the 2017 Lavaman Triathlon. work like dogs. Courtesy of Hawaiiphotoman.com We get up before the sun every day and move massive amounts of material around town to create the route the athletes follow. Most days are long, hot, and busy. On race day, we are up at 1:00 am. The race starts at 7:00 am. The next time we see a pillow is 36 hours later. Even though we are in Hawaii, it’s not a relaxing vacation. So now you’re probably asking yourself, why do we do it?
We stand at the finish line at midnight cheering on the last athletes coming in from a 2.4-mile swim in the ocean, a 112-mile bicycle ride in the wind, and a 26.2-mile run. The energy of the crowd, the families, the volunteers, and the athletes is uplifting. It gets my own heart pounding. For me, knowing that in a small way, I have helped all the athletes complete a grueling physical event and become an Ironman is an emotional reward beyond description. Why am I bringing this up? The NAVC runs on a similar spirit. Without volunteers, the VMX (formerly the NAVC Conference) would grind to a halt. Our volunteers help monitor doors, direct traffic, answer questions, and stuff all those conference bags—just to name a few of their many tasks. They include Past Presidents of the NAVC Board of Directors as well as family members of NAVC staff. Our Board of Directors is made up of volunteer members. Even this journal (and its sister, Today’s Veterinary Practice) runs on volunteers, as our authors and reviewers take time from their busy lives to contribute. We all do it with tremendous enthusiasm, knowing we are providing outstanding, worldclass education for all members of the veterinary healthcare team. Without our volunteers, the NAVC just wouldn’t be the same, and I thank them all. So whatever volunteer act you do that gets your heart racing, makes you smile, laugh, cry, clap, and jump for joy, keep doing it! Volunteering in any way brings a smile to the people you do it for every day. Reference 1. Volunteerism. Dictionary.com Unabridged. dictionary.com. Accessed April 2017.
Do you have a story you’d like to share? Write me at ljohnson@navc.com.
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30 Years of Prevention.
THANK YOU FOR MAKING US A PART OF YOUR TEAM.
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“Saving one dog will not change the world, but surely for that one dog, the world will change forever.” — Karen Davidson, author of A Dog’s Guide to Humans
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1 Credit Continuing Education | Peer Reviewed
To view the CE test for this article, please visit todaysveterinarytechnician.com.
CONTINUING EDUCATION
PEER REVIEWED
M E E T T H E AU T H O R
Critical Components of Successful CPR: The RECOVER Guidelines, Preparedness, and Team In 2011, a trainer for an obedience class faced the dire situation of a dog collapsing and seemingly going into cardiac and respiratory arrest. As the owner laid over her best friend crying in horror, the trainer began performing cardiopulmonary resuscitation (CPR) to the best of his knowledge, providing chest compressions and mouth-to-snout breaths. Several moments into CPR, the dog took an agonal breath; the trainer continued CPR. After several more moments, much to the owner’s, trainer’s, and classmates’ relief, the dog regained consciousness and, although disoriented, tried to get up. The outcome was that the dog and owner were able to go home, seemingly recovered from the event.1 Reviewing the video footage of this incident, we can critique the way CPR was performed and discuss its potential effectiveness in light of evidence-based CPR guidelines established in 2012 by the Reassessment Campaign on Veterinary Resuscitation (RECOVER) Initiative. The RECOVER guidelines were produced through a series of systematic reviews conducted by more than 100 specialists in the field of emergency and critical care and allied specialties. The RECOVER initiative also identified a series of knowledge gaps toward which the veterinary community can direct its investigative efforts to continue to improve the effectiveness of CPR. The guidelines are accessible at no cost (veccs.org/recover-cpr), and veterinary professionals can use them to develop CPR training standards for veterinary teams today.
Kenichiro Yagi, BS, RVT, VTS (ECC, SAIM) Adobe Animal Hospital Los Altos, California Ken practices at Adobe Animal Hospital as an ICU and Blood Bank Manager. He is an active educator, lecturing internationally, providing practical instruction, and authoring texts, chapters, and articles on transfusion medicine, respiratory care, and critical care nursing. He serves on the boards of the Veterinary Emergency and Critical Care Society and the Academy of Veterinary Emergency and Critical Care Technicians, on the Veterinary Innovation Council, and as the NAVTA State Representative Chairperson. He is a graduate student in veterinary medicine and surgery through the University of Missouri. Ken invites all veterinary technicians to ask “Why?” to understand the “What” and “How” of our field and to constantly pursue new limits as veterinary professionals.
FIGURE 1. A properly organized and equipped crash cart located in a central emergency area is critical for swift intervention.
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Critical Components of Successful CPR: The RECOVER Guidelines, Preparedness, and Team PEER REVIEWED
THE RECOVER GUIDELINES ON CPR The guidelines address 5 aspects surrounding cardiopulmonary arrest (CPA): preparedness and prevention, basic life support (BLS), advanced life support (ALS), monitoring, and post–cardiac arrest care. Preparedness and Prevention With the documented rate of successful resuscitation by CPR and survival to discharge being approximately 6%,2 the veterinary team must be prepared for CPA to maximize chances of resuscitation. Preparedness begins with obtaining the knowledge behind CPR as well as psychomotor (physical) training for performing it. Initial training should introduce all key concepts
of CPR; refresher training is recommended at least every 6 months to keep the knowledge current and reinforced. A designated emergency area should be centrally located and fully stocked for performing CPR. The staff should be familiar with an organized crash cart containing necessary supplies, drugs, equipment, and documents, and the cart should be routinely checked (either on a schedule or a per-use basis) to ensure it is properly stocked and that everything is in-date and functional (FIGURE 1). Crucial items include equipment for securing the airway and venous access, emergency medications, monitoring equipment, and other supplies to facilitate CPR and emergency surgical procedures (BOX 1). The emergency area should also contain visual aids,
BOX 1 Crash Cart or Emergency Area Supplies Airway Endotracheal tubes Tube ties Laryngoscope Syringe for cuff inflation Venous IV catheters (24- to 16-gauge) Tape Saline flush Preassembled crystalloid fluid bag and IV sets T-ports and male adapter plugs Scalpel blade and suture (for venous cutdowns) Syringes (1–6 mL) Needles (25- to 18-gauge) Intraosseous (IO) catheter setup (IO drill, bone biopsy needles, or large needles) Medication Standard Epinephrine Atropine Reversal agents: atipamezole, flumazenil, naloxone Anti-arrhythmic agents: amiodarone, lidocaine
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Additional Vasopressin Dopamine Dobutamine Norepinephrine Diazepam/midazolam Furosemide Calcium gluconate Sodium bicarbonate Respiratory Suction machine and tubing Suction catheters or red rubber tubes Manual resuscitator (eg, Ambu bag) Thoracocentesis kit Surgical Tracheostomy tubes Sterile gloves Emergency surgical packs Sterile gauze Scalpel blade and handle Equipment Electrocardiograph Capnometer Defibrillator
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Critical Components of Successful CPR: The RECOVER Guidelines, Preparedness, and Team PEER REVIEWED
such as the CPR algorithm and CPR drug dosage chart (available from veccs.org), which will improve efficiency during the event3 (FIGURE 2). Resuscitation Orders Every animal admitted to the practice should have a designated resuscitation order established via a thorough conversation between the veterinary team and the owner to prevent delays in implementing CPR if needed. Color-coding housing labels, patient charts, or patient tags to indicate the patient’s resuscitation order can reduce confusion. Patients with a chronic disease that has progressed to the point of causing CPA are less likely to respond to CPR. CPA as a consequence of an acute condition is more likely to have a successful outcome. Otherwise healthy patients that arrest because of an anesthetic event have a much higher chance of survival, reported to be 47% in one study.2 Every effort should be made to ensure the resuscitation order is appropriate for the patient by accurately assessing its chances of survival. Basic Life Support BLS is the attempt to sustain life by artificially maintaining blood flow and oxygenation of the blood. Blood flow is created through chest compressions while positive-pressure ventilation (PPV) provides oxygen and removes carbon
FIGURE 2. Large cognitive aids posted in the emergency area can improve the efficiency of and consistent adherence to guidelines by the CPR team.
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dioxide from the pulmonary circulation. An unresponsive patient should be assessed for possible arrest through auscultation of the heart, palpation for pulses, and observation for breathing.4 The assessment should take no longer than 10 to 15 seconds, and BLS should be initiated as soon as possible once CPA is identified.5 It can be argued that BLS should be commenced as soon as possible even when CPA cannot be confirmed: research shows that A
B
C
FIGURE 3. (A) For round-chested dogs (chest as wide as it is deep), compressions are focused on the widest point of the chest. (B) For narrow-chested dogs (chest deeper than it is wide), compressions are focused over the heart. (C) Some dogs might be considered to be flat-chested by typical breed conformation, but each individual should have its conformation assessed for the optimal compression point. This dog would benefit from compressions on the widest point of the chest in lateral recumbency. If the patient is truly wider than it is deep, then compression over the sternum (red arrow) is reasonable.
T E C HP O I N T
The RECOVER guidelines establish a standard and benchmark against which veterinary professionals can evaluate their CPR methods and training. rescuers can be unreliable in accurately assessing presence of pulses; there is no evidence that initiating compressions when an animal is not in arrest causes significant harm; and commencing CPR with as little delay as possible improves outcome.6 When CPR is initiated, the algorithm of CAB (circulation, airway, breathing) is followed instead of ABC (airway, breathing, circulation) as blood flow is most important and chest compressions provide ventilation even before intubation and provision of PPV.5 Circulation Chest compressions are performed to create as much blood flow as possible to the pulmonary tissues for gas exchange and to deliver oxygen to tissues to support metabolism and restore organ function, ideally achieving return of spontaneous circulation (ROSC). Even the most effectively administered compressions provide only 30% of normal cardiac output, making consistent application of best practices during CPR compressions critical.5 Chest compressions are recommended to be performed at a rate of 100 to 120/min regardless of species and size and forceful enough to compress the chest one-third to one-half of normal width. Compressions should be performed in 2-minute cycles without interruption; this is because 60 seconds of consistent compression is required for myocardial
Peer Reviewed
CONTINUING EDUCATION
perfusion pressure (MPP) to reach its maximum potential, and every second of interruption leads to significant decreases. Thus, any patient assessment (eg, electrocardiography [ECG], pulse palpation, auscultation) should be limited to several seconds between the 2-minute cycles to prevent complete loss of accumulated MPP. Two minutes of uninterrupted chest compressions is physically taxing, and switching the compression provider for each cycle is recommended. Physical aspects of chest compressions include the provider superimposing his or her palms (ie, stacking the hands flat, with the palm of one on the back of the other) and creating downward motion onto the patient through a “compression point” (as opposed to an “area”). The compression point depends on the conformation and size of the patient, which should be evaluated individually, even though breeds are associated with each type (FIGURE 3). Round-chested dogs (chest as wide as it is deep) benefit from compressions focused on the widest part of the chest cavity with the patient in lateral recumbency, with the goal of creating intrathoracic pressure and thus using the thoracic pump theory. In this model, the increased intrathoracic pressure applied to the vasculature within the thoracic cavity creates forward blood flow. Release of pressure allows the rib cage to recoil open, creating negative pressure to pull blood from the abdomen into the thoracic cavity, which is then pushed forward again with the subsequent compression.
FIGURE 4. Small dogs and cats can have compressions focused over the heart with one hand.
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Critical Components of Successful CPR: The RECOVER Guidelines, Preparedness, and Team PEER REVIEWED
In dogs with a narrow or keeled chest (deeper than it is wide), the cardiac pump theory is applied by focusing compressions over the heart while the patient is in lateral recumbency. Each compression physically pushes blood out of the heart, while each recoil allows blood to flow in. For flat-chested dogs (ie, the chest is truly wider than it is deep), compressions should be focused over the sternum with the dog in dorsal recumbency, to employ the cardiac pump theory. In small dogs and cats, compressions can be performed directly over the heart while in lateral recumbency, using a single- or two-handed method (FIGURE 4). In animals with conformation requiring lateral recumbency, there is no evidence indicating whether right or left lateral recumbency is more effective.5 Key aspects of the physical positioning of the compression provider include (1) superimposed palms, (2) locked elbows, and (3) standing at a sufficient height to place the shoulders directly above the patient. This height can be achieved by standing on a step stool or by kneeling safely on the same surface as the patient (whether it be the table or the floor). The downward force should be created by the core muscles of the abdomen rather than the arms, allowing stronger exertion of force and longer sustainability (FIGURE 5). The use of such aids as a metronome can help maintain specified compression rates; A
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“Stayin’ Alive,” Bee Gees “Paradise City,” Guns N’ Roses “Rock Your Body,” Justin Timberlake “Suddenly I See,” KT Tunstall “Back To Life,” Soul II Soul
training to perform compressions to familiar songs of the appropriate beat can be helpful as well (BOX 2). More recently, devices designed to provide audio cues for timing compressions, ventilations, and 2-minute cycles have become available (FIGURE 6). Ventilation Ventilation should be started as soon as possible once compression is initiated. Endotracheal intubation is performed with the patient in lateral recumbency without interruption of compressions, and the cuff is inflated so that PPV is directed into the lungs instead of into the stomach or out the mouth. Breaths are provided 10/minute at a tidal volume of 10 mL/kg over a 1-second inspiration time through the reservoir bag of an anesthetic
B
FIGURE 5. Positioning for chest compressions. (A) Forward view demonstrating superimposed palms and locked elbows. (B) Side view demonstrating the shoulders positioned directly over the patient in a perpendicular manner.
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BOX 2 Songs With a Beat of Approximately 100/minute
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FIGURE 6. An auditory timing aid device for veterinary CPR.
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Critical Components of Successful CPR: The RECOVER Guidelines, Preparedness, and Team PEER REVIEWED
machine or a manual resuscitator (FIGURE 7). If a spirometer is not available, a manometer reading of 20 cm H2O indicates consistent breaths. The reduced respiratory rate of 10 breaths/minute and subsequently low per-minute ventilation (approximately 100 mL/kg/min versus the normal 200 mL/kg/min) are tolerable because of the reduced pulmonary blood flow during arrest. Keeping the breath size and frequency consistent also helps prevent eliminating too much carbon dioxide and thereby causing hypocapnia through hyperventilation, which would cause cerebral vasoconstriction and impair blood flow to the brain. If endotracheal tubes are unavailable, mouthto-snout ventilation can be used, although its efficacy in providing adequate ventilation and oxygenation is currently unknown.4 Mouth-tosnout ventilation is performed by closing the animal’s mouth and keeping the neck in alignment with the spine while the rescuer blows through his/her mouth into the nares of the patient. The recommended compression:ventilation ratio is 30:2, with the breaths delivered and chest excursion observed briskly—each inspiration should last no longer than 1 second—to avoid further interruption of chest compressions.5 Keeping the inspiration time consistently short also mitigates the reduction of venous return that can be caused by increased intrathoracic pressure from PPV coinciding with compressions.5
FIGURE 7. Positive-pressure ventilation can be performed with a reservoir bag on the anesthetic machine.
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Advanced Life Support ALS includes measures (eg, drugs, defibrillation) beyond those to sustain basic life (compression and ventilation) that provide additional support for the patient. However, all ALS interventions are unlikely to lead to ROSC without effective BLS measures and thus should be instituted without interruption of appropriate BLS.5 Medications During CPR A variety of drugs are used during CPR to maximize chances of ROSC. Administration through the IV or intraosseous (IO) route is appropriate. While venous access might already be established in hospitalized animals, swift establishment of venous access is necessary for patients brought into the emergency room in CPA. Procedures such as venous cutdown or IO catheter placement can minimize the time required to establish venous access but should not interrupt BLS interventions. In larger patients arriving in arrest, the use of an IO drill stored in a designated location can reduce the time required to establish venous access to 30 to 60 seconds (FIGURE 8). Drugs used in CPR include vasopressors, parasympatholytics, reversal agents, antiarrhythmics, IV fluids, and alkalinizing agents (TABLE 1).
FIGURE 8. An intraosseous catheter driver can facilitate venous access in emergency cases. The photo demonstrates tibial placement with an electric intraosseous driver. The femur and humerus may be used for manual placement as needed and able.
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Vasopressors Epinephrine is the most commonly used vasopressor during CPR, serving to cause vasoconstriction through its action on the α1, β1, and β2 receptors to redirect the blood flow from the periphery to the body core and vital organs.5 Two epinephrine dosages are specified by the RECOVER guidelines. The low dose (0.01 mg/kg IV or IO) is associated with a higher rate of survival to discharge, while the high dose (0.1 mg/kg IV or IO) is associated with a higher rate of ROSC. Note that although the high dose may be more likely to induce ROSC, the chance of survival to discharge is lower, possibly related to reduced perfusion to vital organs due to severe vasoconstriction.7 Epinephrine is dosed once every 3 to 5 minutes, making every other compression cycle an ideal time for administration. Epinephrine can be administered via the intratracheal route at twice the IV/IO dose; a long catheter is used to administer the drug diluted 1:1 with saline or sterile water into the lower airway through
CONTINUING EDUCATION
the endotracheal tube5; however, this route should be used only when venous access is not possible as the effect of the drugs remaining in the airway upon ROSC is difficult to predict. Vasopressin, which acts on vascular smooth muscles through the V1 receptor to cause vasoconstriction, can be used in lieu of or in conjunction with epinephrine for the same effects. No additional harm caused by the use of vasopressin over epinephrine has been observed, and there might be potential benefits such as responsiveness in acidic environments and a lack of inotropic and chronotropic effects that can add to myocardial ischemia when ROSC is achieved.5,7 The suggested dosage for vasopressin is 0.8 U/kg IV or IO, and it can be administered intratracheally as described for epinephrine. Parasympatholytics Atropine is a parasympatholytic commonly used in CPR at 0.04 mg/kg IV or IO every
TABLE 1 Medications Used During CPR5 TYPE
NAME
DOSE
USAGE
Arrest
Epinephrine (low dose)
0.01 mg/kg IV or IO 0.02-0.1 mg/kg IT
Every other compression cycle
Epinephrine (high dose)
0.1 mg/kg IV, IO, or IT
In prolonged CPR (>10 min)
Vasopressin
0.8 U/kg IV or IO 1.2 U/kg IT
Every other compression cycle, in lieu of or in conjunction with epinephrine
Atropine
0.04 mg/kg IV or IO 0.15-0.2 mg/kg IT
Beneficial in bradycardic arrest or high vagal tone
Bicarbonate
1 mEq/kg IV or IO
Prolonged CPR, pH <7.0
Amiodarone
5 mg/kg IV or IO
Refractory VF, pulseless VT May cause hypotension/anaphylaxis
Lidocaine
2 mg/kg IV or IO slow (1-2 min)
Alternative to amiodarone
Atipamezole
50 mcg/kg IV or IO
α2 agonist reversal
Flumazenil
0.01 mg/kg IV or IO
Benzodiazepine reversal
Naloxone
0.04 mg/kg IV or IO
Opioid reversal
Monophasic
4-6 J/kg (external) 0.5-1 J/kg (internal)
For VF and pulseless VT Administer immediately if within 4 minutes of onset, otherwise after compression cycles
Biphasic
2-4 J/kg (external) 0.2-0.4 J/kg (internal)
Can increase dose by 50% each cycle up to a maximum of 10 J/kg
Antiarrhythmic
Reversal
Electrical defibrillation
IO, intraosseous; IT, intratracheal; IV, intravenous; VF, ventricular fibrillation; VT, ventricular tachycardia.
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Critical Components of Successful CPR: The RECOVER Guidelines, Preparedness, and Team PEER REVIEWED
other compression cycle. While there are no high-quality studies showing clear benefits of its use in CPR, there is no evidence of harm. Atropine is thought to be beneficial in patients with asystole or PEA, especially those suspected to be experiencing high vagal tone (eg, vomiting, ileus, gastrointestinal disease, respiratory disease).5,7 Intratracheal administration is also possible at 0.08 mg/kg. Reversal Agents If patients in CPA were under the influence of any reversible anesthetic agent or sedation, reversal of said agent could improve the chances of successful outcome. Atipamezole, flumazenil, and naloxone are readily available reversal agents for α2 agonists, benzodiazepines, and opioids, respectively. Antiarrhythmic Agents While no evidence supports the routine use of antiarrhythmics in CPR, administration of amiodarone has been suggested for patients with VF refractory to electrical defibrillation. Hypotension and anaphylactic reactions have been documented in dogs receiving amiodarone, and careful monitoring is recommended following ROSC.5,7 Lidocaine can be administered to patients with refractory VF, although the evidence regarding its benefits is mixed.7 Intravenous Fluids The use of IV fluids during CPR largely depends on the state of IV fluid balance in the patient. IV fluids are beneficial for patients experiencing hypovolemia as the increased intravascular volume leads to better preload, improving chances of creating effective blood flow through chest compressions. Not every patient benefits from IV fluids, however, as euvolemic or hypervolemic individuals can become overloaded with fluids, which leads to increased central venous pressure that can in turn reduce MPP and cerebral perfusion pressure.5 Electrolyte disturbances can be a contributor to CPA or a result of metabolic acidosis, drug therapy, and other interventions. No evidence of benefit exists
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for correcting electrolyte disturbances other than severe hyperkalemia or hypocalcemia.7 Alkalinizing Agents Routine administration of alkalinizing agents, such as sodium bicarbonate, as a buffer for metabolic acidosis is not recommended, but these agents can be considered for prolonged CPA because severe acidemia can affect the vasculature’s ability to respond to vasopressors and impair normal enzymatic functions. Administration of sodium bicarbonate is accompanied with a cautionary note that it can lead to alkalemia and paradoxic cerebral and metabolic acidosis.7 It is recommended that sodium bicarbonate be reserved for severe acidemia (pH <7.0) in prolonged CPR.5 Electrical Defibrillation When a patient is experiencing VF, electrical defibrillation is the appropriate therapy to convert to normal rhythm. The approach to electrical defibrillation depends on the phase of VF. In the first phase, which lasts approximately 4 minutes, the heart experiences minimal ischemia and has enough energy reserves to carry on metabolic processes. In the second phase (subsequent 6 minutes), the heart experiences reversible ischemic damage as the energy reserves in the form of ATP are depleted. In the third phase, the heart experiences irreversible ischemic damage as energy stores are exhausted.5 If the patient is in the first phase of VF, it should be defibrillated as soon as the defibrillator is charged, allowing for interruption of chest compressions as the cellular energy reserves of the heart makes successful defibrillation more likely. If the patient is suspected to be in the second phase or beyond, a full cycle of chest compressions should be performed before defibrillation to allow for replenishing of some cellular energy to improve chances of success.5 Electrical defibrillation is also warranted when the patient is experiencing pulseless ventricular tachycardia. VF and pulseless ventricular tachycardia are referred to as “shockable rhythms” based on their responsiveness to defibrillation. When a shockable rhythm is identified during assessment between compression cycles, chest
T ECHP O I N T
Two minutes of uninterrupted chest compressions is physically taxing, and switching the compression provider for each cycle is recommended.
compression should be resumed and a full 2-minute cycle completed as the defibrillator is allowed to charge. Defibrillation should be performed after the completion of the compression cycle. The dosing of electrical defibrillation depends on the type of defibrillator. Monophasic defibrillators are dosed at 4 to 6 J/kg and biphasic defibrillators at 2 to 4 J/kg. Biphasic defibrillators are preferred because of their ability to defibrillate with lower energy output, leading to less myocardial damage. Chest compressions should be resumed immediately after electrical discharge while the defibrillator is charged for another dose. ECG should be assessed after the compression cycle is completed to determine if the shockable rhythm is still present and another dose is needed.5
Peer Reviewed
CONTINUING EDUCATION
created through compressions (FIGURE 9). In addition, measurement of ETCO2 can be used to confirm that the endotracheal tube is in the trachea because significant CO2 is unlikely to be measured from the esophagus. However, a lack of measurement does not necessarily indicate esophageal placement, as ineffective compressions and poor pulmonary circulation will not produce CO2. During CPR, maintenance of ETCO2 above 10 to 15 mm Hg is favorable for the patient in achieving ROSC, whereas chances of ROSC were observed to be lower below these values.5 Capnography can also serve as an indicator for ROSC because the values will increase significantly, likely to hypercapnic values, upon re-establishment of pulmonary circulation from spontaneous cardiac output. Electrocardiography ECG, which assesses the electrical activity of the heart, is a valuable monitoring modality during CPR. Between compression cycles, ECG can be monitored to determine spontaneous electrical activity (FIGURE 10). During the compression cycle, mechanical action will be detected, and it is difficult to distinguish between mechanical and spontaneous activity (FIGURE 9). Asystole is the most common arrest rhythm, in which case compressions should be resumed. The patient may exhibit
Monitoring Monitoring during CPR can be best accomplished through the use of capnography and electrocardiography (ECG). Capnography Monitoring end-tidal carbon dioxide (ETCO2) values during CPR is the most useful method to assess the effectiveness of compressions in creating blood flow and lung perfusion. Because minute ventilation is relatively consistent during CPR, the measured ETCO2 value will increase in proportion to the pulmonary blood flow
FIGURE 9. The screen of a multiparameter ECG monitor during CPR. The ECG is registering mechanical action exerted by the compressions (blue circle). The capnography (yellow circle) is displaying a breath (larger plateau) and compression-induced ventilation (small spikes). The ETCO2 measurement (red circle) is reading 6 mm Hg and 11 breaths/min.
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Critical Components of Successful CPR: The RECOVER Guidelines, Preparedness, and Team PEER REVIEWED
electrical activity without any palpable pulse, or pulseless electrical activity (PEA), in which case compressions should be resumed. The possibility of PEA also highlights the importance of confirming actual pulses after visualizing electrical activity on ECG. Ventricular fibrillation (VF) is less common and is treated through defibrillation if present. Multiple members of the CPR team should be observing the ECG readout during the assessment period between compression cycles to clearly communicate the rhythm and swiftly move to the next step. Post–Cardiac Arrest Care For patients that recover from CPA and achieve ROSC, post–cardiac arrest care includes respiratory status optimization, cardiovascular system support and optimization, and neuroprotective therapy. An algorithm for postarrest care is provided in the RECOVER guidelines. Care for a patient after achieving ROSC is an A
B
C
intensive process, with ROSC being only the first hurdle to overcome toward actual survival to discharge; a patient that has arrested once is likely to re-arrest during this period. TEAM DYNAMICS Team Structure The presence of a CPR team leader significantly improves the flow during CPR. The leader is responsible for assigning roles to team members (TABLE 2), enforcing protocol, and facilitating communication. Intermittently summarizing the current status of the CPR attempt, soliciting input from team members, and organizing changes in roles and next steps are all important tasks performed by the CPR leader. Specific training for those taking on the role of a CPR leader is recommended. At my place of employment, the role of CPR team leader, usually a veterinary technician, is intentionally assigned to someone other than the attending veterinarian to allow the CPR team and veterinarian to function independently. The CPR leader focuses on organizing the CPR, assigning roles, and directing the CPR flow. The veterinarian makes medical decisions, fills no other roles, focuses on patient diagnosis and treatment, and communicates with the client. This veterinarian and CPR team arrangement has greatly enhanced our ability to manage the controllable factors of CPR and prevent delays and mistakes from splitting the veterinarian’s attention between the patient, client, and CPR flow (FIGURE 11).
TABLE 2 Team Roles During CPR D
FIGURE 10. Possible ECG tracings during CPR. (A) Asystole, with no regular electrical activity. (B) PEA: no palpable pulses are being produced even though electrical activity is seen. (C) Another example of PEA. (D) Ventricular fibrillation: nonorchestrated discharge of electrical activity leading to ineffective cardiac output. Courtesy of Kristie Garcia, LVT, VTS (Cardiology)
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ROLE
TASKS
Compression
Chest compressions (alternated)
Airway management
Establish airway Ventilate
Drug administration
Establish venous access Administer drugs
Recorder
Document events Time events
CPR leader
Organize CPR
Veterinarian
Manage patient
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Communication Surrounding CPR Closed-Loop Communication During CPR, the closed-loop communication method is recommended. This consists of instructions being given clearly and directed at one individual, who then repeats the instruction to confirm accurate communication. Closedloop communication reduces the chances of medical errors due to misunderstanding or missing instructions and helps orient other team members about the status of CPR flow. CPR Flow Sheet A well-designed sheet to record pertinent details related to the CPR attempt is recommended (FIGURE 12). A standard record sheet serves as a checklist for tasks and roles required during CPR, provides documentation of specific events (eg, timing of last drug administration) during CPR, and enables review after CPR. A properly maintained database of details regarding CPR and outcomes allows the practice to track the effectiveness of CPR. The RECOVER initiative has also published guidelines for standardized reporting of in-hospital veterinary cardiac arrest and CPR and is working on establishing a global registry to gather more information surrounding CPR to address unanswered questions and improve the guidelines.8
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Debriefing After a CPR event, a debriefing session is recommended to review and critique the performance from both an individual and team perspective. Debriefing sessions allow errors to be identified and provide an opportunity to develop plans for improvement by correcting any issues. The session is designed to let team members discuss the decisions made, actions taken, and possible alternatives; identify any need for training; and recognize each other for successful actions.9 Adequate debriefing can be conducted in 5 to 10 minutes by the team leader. Questions should include “What went well with this CPR session?”, “What could have been done better?”, and “Are there any major issues to report to the CPR committee?” Open and transparent discussion in a safe environment is vital to effective debriefing, which leads to both individual and team improvement6 (FIGURE 13). THE FUTURE OF VETERINARY CPR The RECOVER guidelines establish a standard and benchmark against which veterinary
Please affix cage label here
Date: ______________ Time Event Recognized: ______________ Event ☐ Witnessed ☐ Cardiac Arrest ☐ Not Witnessed ☐ Respiratory Arrest Breathing immediately prior to CPCR: ☐ Spontaneous ☐ Apneic ☐ Agonal ☐ Assisted Ventilation: ☐ Endotracheal Tube ☐ Mask / Valve / Bag ☐ Tracheostomy ☐ Other: ____________ Intubation: Patient Name: Time: ____________ Size: _______________ By Whom: ______________________________ Placement confirmation via: Acct Number: ☐ Auscultation ☐ Exhaled CO2 ☐ Other: ___________________ Compressions: ☐ Manual ☐ None Start Time: ______________ Thoracotomy: Time: ___________ By Whom: ________________________ Epinephrine
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Comments Initials of person administering meds, IV catheter, I/O catheter, person
Additional comments: _______________________________________________________________________________ _________________________________________________________________________________________________ _________________________________________________________________________________________________ Time Resuscitation Event Ended: ______________ Status: ☐ Alive ☐ Deceased Reason Resuscitation Ended:
FIGURE 11. A structured CPR team. Separate roles between CPR leader (pink scrubs) and veterinarians (brown scrubs and red scrubs) allow for uninterrupted CPR while the case is discussed.
☐ Return of Circulation (ROSC)
☐ Efforts Terminated (No sustained ROSC)
☐ Medical Futility Clinician: _______________________________ Team Leader: ______________________________ Ventilator: ______________________________ Drug Handler: ______________________________ Compressors: ____________________________________________________________________________ Recorder: _________________________________
FIGURE 12. Sample CPR record form.
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Critical Components of Successful CPR: The RECOVER Guidelines, Preparedness, and Team PEER REVIEWED
professionals can evaluate their CPR methods and training. The need for standardized guidelines regarding veterinary CPR is well recognized internationally, and to date, the RECOVER guidelines have been translated into Portuguese, Spanish, Japanese, and Mandarin. All of RECOVER’s information will be housed on a central Internet resource to be available worldwide (recover-initiative.org). The RECOVER initiative is being updated, with publication planned in 2018. The 2012 RECOVER review process revealed knowledge gaps that are intended to be filled through ongoing research in the field, with the RECOVER initiative directly contributing. The establishment of the global registry and a standardized record sheet will allow each practice to contribute to the data collection, and additional methods are planned. Through the process, the RECOVER initiative has pioneered a large-scale evidence-based guideline creation process that is translatable to a variety of topics in veterinary medicine. Both online and physical CPR certification courses have been created and approved by the American College of Veterinary Emergency Critical Care and the Veterinary Emergency and Critical Care Society. Certification for the psychomotor training is being expanded through the establishment of an official trainer network to significantly increase global accessibility. For veterinary
FIGURE 13. A debriefing session enhances the team dynamics and facilitates further improvement of CPR through open and transparent communication.
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professionals, preparedness for CPA through certificate training should be considered a standard in practice. The training is reaching other animal workers and the lay public to improve chances of resuscitation for out-of-hospital arrests as well. CONCLUSION Veterinary technicians play a critical role in assessing patients at risk of experiencing CPA and swiftly initiating CPR when necesssary. While the current success rate and the rate of survival to discharge are expectedly low, establishment of organized training based on an evidence-based protocol such as RECOVER is a duty of the veterinary team to ensure the best possible chance of a positive outcome. Acknowledgment The author would like to thank Dr. Manuel Boller and Dr. Dan Fletcher for providing the latest information on the plans of the RECOVER Initiative. References 1. Ellis S. Man uses CPR, saves dog’s life. Global Animal [website]. March 29, 2011. globalanimal.org/2011/03/29/ man-uses-cpr-saves-dogs-life-video. Accessed March 2017. 2. Hofmeister EH, Brainard BM, Egger CM, et al. Prognostic indicators for dogs and cats with cardiopulmonary arrest treated by cardiopulmonary cerebral resuscitation at a university teaching hospital. JAVMA 2009;235(1):50-57. 3. McMichael M, Herring J, Fletcher DJ, et al. RECOVER evidence and knowledge gap analysis on veterinary CPR. Part 2: Preparedness and prevention. J Vet Emerg Crit Care 2012;22(S1):S13-S25. 4. Hopper K, Epstein SE, Fletcher DJ, et al. RECOVER evidence and knowledge gap analysis on veterinary CPR. Part 3: Basic life support. J Vet Emerg Crit Care 2012;22(S1):S26-S43. 5. Fletcher DJ, Boller M. Cardiopulmonary resuscitation. In: Silverstein D, Hopper K (eds). Small Animal Critical Care Medicine. 2nd ed. St Louis: Elsevier; 2015. 6. Fletcher DJ, Boller M, Brainard BM, et al. RECOVER evidence and knowledge gap analysis on veterinary CPR. Part 7: Clinical guidelines. J Vet Emerg Crit Care. 2012;22(S1):S102-S131. 7. Rozanski EA, Rush JE, Buckley GJ, et al. RECOVER evidence and knowledge gap analysis on veterinary CPR. Part 4: Advanced life support. J Vet Emerg Crit Care 2012;22(S1):S44-S64. 8. Boller M, Fletcher DJ, Brainard BM, et al. Utstein-style guidelines on uniform reporting of in-hospital cardiopulmonary resuscitation in dogs and cats. A RECOVER statement. J Vet Emerg Crit Care 2016;26(1):11-34. 9. Salas E, Klein C, King H, et al. Debriefing medical teams: 12 evidence-based best practices and tips. Jt Comm J Qual Patient Saf 2008;34(9):518-527.
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M E E T T H E AU T H O R
Doxorubicin: An Overview
Emily Fullerton, RVT, VTS (Oncology) VCA Veterinary Referral Associates Gaithersburg, Maryland
Shutterstock.com/Belu Gheorghe
As in human medicine, the veterinary “nurse” is a jack of all trades. A veterinary technician’s role in the oncology world is not only to have excellent technical skills but also to also be warm and compassionate, be a patient advocate, and make connections with and educate clients. Treating patients with chemotherapeutics requires a thorough understanding of the risks and handling of these agents. In addition, in the face of a chemotherapeutic spill or extravasation, it is necessary to know and act on the immediate response protocol. Doxorubicin is one of the most dangerous chemotherapeutics used in veterinary oncology. However, it is also one of the most common and efficacious treatments for several types of canine and feline malignancies (see DOXORUBICIN IN THE TREATMENT OF SPECIFIC CANCERS1–12).
Emily obtained her associate’s degree from Vet Tech Institute in December 2008, leading her to her registered veterinary technician license in January 2009. She subsequently moved to Maryland, where she found her place in veterinary medicine: medical oncology. With her passion for helping animals and support from her coworkers, she achieved her Veterinary Technician Specialist certification in oncology in 2014. Emily has a love of food and wine, her own fuzzy pets, and spending time with her family.
HISTORY Sometimes referred to as the “red death,” doxorubicin is red in color and originates from a product of a fungus (Streptomyces). It is considered part of the anthracycline antitumor antibiotic class of chemotherapeutics. Its antitumor properties were first discovered more than 45 years ago, when it was being used as an antibiotic and tested on tumor-bearing mice; early dosing
THE GREAT DANE is a canine breed that is known to be prone to dilated cardiomyopathy. Before treatment using doxorubicin, such breeds should be evaluated by a cardiologist to search for any evidence of myocardial dysfunction.
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Doxorubicin: An Overview PEER REVIEWED
and frequency studies were performed on dogs.13 Cardiotoxic effects were first noted during human testing in the late 1960s. Fourteen children died during the study; 7 had cardiopulmonary complications.13 CARDIOTOXIC EFFECTS Veterinary studies of doxorubicin were first published in the late 1970s. Hundreds of published studies have since investigated its use. Clinically relevant cardiotoxicity is uncommon in cats when appropriate doses are used, but the cardiotoxic effects noted in humans have been observed in dogs (FIGURE 1). Several mechanisms for these effects have been proposed, but the most studied theory is that doxorubicin interacts and releases iron from storage proteins, causing the creation of reactive superoxide molecules, or oxidative free radicals.14 The exact mechanism of iron and free radical damage as it relates to cardiotoxicity secondary to doxorubicin is unknown. Cardiac side effects of doxorubicin are cumulative and irreversible. They can occur at any time during the treatment protocol, even during administration if doxorubicin is given too quickly.15 Extreme caution should be used when cumulative doses reach 180 to 240 mg/m2. Prevention A few measures can be taken to help reduce the risks of doxorubicin-induced cardiomyopathy, including evaluation by a cardiologist before treatment. The cardiologist will perform such tests as echocardiography and electrocardiography (ECG) to search for
any evidence of myocardial dysfunction. This is especially recommended for breeds that are known to be prone to dilated cardiomyopathy (BOX 1). It is recommended that any patient that develops heart murmurs or arrhythmias while on doxorubicin chemotherapy be evaluated by a cardiologist.6 Echocardiography and ECG are also recommended when a patient requires doses beyond the lifetime margin of safety of 180 to 240 mg/m2. A small study of the side effects of doxorubicin in cats showed that echocardiographic changes consistent with doxorubicin-induced cardiomyopathy occurred in 4 of 6 cats after cumulative doses of 170 to 240 mg/m2 were given.16 Because doxorubicin is usually dosed at 25 mg/m2 or less for cats, and most protocols only include 4 to 5 treatments, this is not usually a clinical concern in this species. Dexrazoxane (Zinecard; pfizer.com) is a cardioprotectant intravenous drug that chelates to iron ions, thus reducing the number of ions that are available for doxorubicin to release and consequently decreasing the formation of superoxide radicals. Although this sounds like a solution to the toxic properties of doxorubicin, dexrazoxane is very expensive, and high doses need to be given to adequately protect the heart—10 times those of doxorubicin (eg, a 30 kg/0.976 m2 dog would need almost 300 mg)— making it difficult for some owners to afford.17
BOX 1 Canine Breeds Predisposed to Dilated Cardiomyopathy Afghan hound American cocker spaniel Boxer Dalmatian Doberman pinscher English cocker spaniel Great Dane Newfoundland
FIGURE 1. Electrocardiogram showing normal PQRST wave (blue arrows) and preventricular contractions (red arrows) caused by doxorubicin.
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St. Bernard
T ECHP O I N T
A veterinary technician’s role in the oncology world is not only to have excellent technical skills but also to also be warm and compassionate, be a patient advocate, and make connections with and educate clients. Dexrazoxane is available in 250 and 500 mg sterile vials and is reconstituted with sodium lactate to a concentration of 10 mg/mL.18 The patient dose is then further diluted with sterile 0.9% NaCl or 5% dextrose solution to a concentration of 1.3 to 5 mg/mL.19 The infusion is given intravenously over 15 minutes, and doxorubicin administration should follow within 30 minutes of finishing the infusion. ADMINISTRATION Doxorubicin must always be administered through a clean, “one stick” intravenous catheter. The vein being used should be intact and should not have been used within the 24 to 48 hours before doxorubicin administration. Doxorubicin is diluted with sterile 0.9% sodium chloride or 5% dextrose solution; the dilution ratio may vary by hospital. The vein should be continually monitored for any sign of extravasation, and blood drawback confirmation is necessary before every push of doxorubicin. Institutions administering doxorubicin must have an extravasation protocol and easy access to the supplies needed to carry it out, including dexrazoxane. To avoid acute adverse effects, doxorubicin is administered as a carefully controlled slow infusion, generally over 15 to 20 minutes. Adverse
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effects can include acute vomiting, nausea, hives, blood pressure changes, and arrhythmias and are attributed to an anaphylactic response and a release of histamine. During doxorubicin administration, it is the veterinary technician’s responsibility to be alert and in tune with the patient’s demeanor. Noticing a change in the patient’s behavior during administration could mean catching an acute side effect before it manifests and reversing it. Patients experiencing acute side effects may hypersalivate; become restless or lethargic; have pale or injected mucous membranes; develop hives, facial swelling, or wheals; or vomit. A general guideline for veterinary technicians administering doxorubicin is to know the patient and be alert to any changes during doxorubicin administration. If an anaphylactic response is suspected, the administration of doxorubicin should be paused. Administration of an antihistamine (diphenhydramine 3–4 mg/kg IM), and a corticosteroid (dexamethasone sodium phosphate 0.5–1 mg/kg IV) is recommended.17 The doxorubicin administration can be finished, at a much slower rate, when the patient’s clinical signs subside. When doxorubicin is administered at a slow rate, acute adverse effects are infrequent. Before initiation of doxorubicin treatment, baseline staging tests such as a complete blood cell count, serum chemistry, and urinalysis should be performed. Doxorubicin should be used with caution in feline patients with known renal dysfunction.16 Doses can be reduced in these patients, but judicious monitoring of renal values and urine concentration is recommended, ideally before administration of each dose. EXTRAVASATION Doxorubicin tissue extravasation has the potential to be catastrophic. This is one of the main reasons that only trained personnel should handle doxorubicin. Extravasation, or leaking of a drug outside of a vein, of some chemotherapeutics can cause mild to moderate tissue irritation, but doxorubicin can cause tissue sloughing, necrosis, and wounds that can take months to heal and may require amputation.
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Doxorubicin: An Overview
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BOX 2 Doxorubicin Extravasation Protocol 1. W ithout removing the IV catheter, draw back as much of the chemotherapy agent as possible. 2. Remove catheter. 3. Apply cold compress for 15-minute periods every 4 to 8 hours for the first 24 hours. 4. Place an IV catheter in a different vein to administer dexrazoxane*:
a. Within the first 2 hours
b. 24 hours after extravasation
c. 48 hours after extravasation
Other considerations: Send all patients home with Elizabethan collars
TECHPOINT
Veterinary technicians who handle doxorubicin must understand the emergency procedures necessary in the event of extravasation, including the dose, proper administration, and availability of dexrazoxane.
Apply Synotic (DMSO) to the area Consider NSAIDs and other pain medications for these patients *Dexrazoxane is dosed at 10 times the dose of doxorubicin, diluted with 0.9% NaCl at a ratio of 1:1, and given over 15 minutes.
Veterinary technicians who handle doxorubicin must understand the emergency procedures necessary in the event of extravasation, including the dose, proper administration, and availability of dexrazoxane. If extravasation is suspected, the doxorubicin infusion should be terminated and every attempt made to draw back as much of the doxorubicin product from the catheter as possible before the catheter is removed. Application of a cold compress promotes vasoconstriction and decreases diffusion of doxorubicin into the surrounding tissues. The dosing and dilution ratio of dexrazoxane are the same as if it is being used for its cardioprotective properties. In a small study of 4 dogs with doxorubicin extravasation, 3 patients showed resolution of lesions with medical management alone after
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the extravasation was treated with dexrazoxane within 2 hours.20 Repeated doses at 24 and 48 hours after the event may also improve outcome. To prevent additional trauma that will perpetuate the wound, an Elizabethan collar is advised. Administration of NSAIDs and pain medications should be considered. Application of a cold compress to the area for periods of 15 minutes multiple times during the first 24 hours may also help mitigate the effects of doxorubicin extravasation. The benefits of applying topical dimethyl sulfoxide (DMSO) to the area of extravasation are unclear. However, DMSO is recommended by many oncologists in the event of an extravasation for the following reasons20: ÆÆ It decreases pain by blocking nerve conduction fibers. ÆÆ It reduces inflammation and swelling. ÆÆ It improves blood supply and oxygen delivery via its vasodilation properties. ÆÆ It is one of the most potent free radical scavengers. BOX 2 provides an example of an extravasation protocol.
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oncology team work with owners to decide the severity of the event (eg, vomiting, diarrhea, inappetence) and helps oncologists make treatment recommendations and decisions.
ADVERSE EFFECTS Doxorubicin has the potential to cause some of the most severe delayed adverse effects of any drug in veterinary oncology. In general, delayed effects can be grouped into gastrointestinal, hematologic, organ toxicosis, and other. Most adverse effects can be handled with ancillary medications that the owners can give at home. In fact, <5% of patients have side effects so severe that they need to be hospitalized. In an effort to help veterinary oncologists quantify chemotherapy toxicities, or adverse events, the Veterinary Cooperative Oncology Group (VCOG) has established grading criteria for different types of adverse events (TABLE 1).21 This grading system helps the veterinary
Gastrointestinal The gastrointestinal tract is lined with rapidly dividing cells, much like those of malignant tumors. Doxorubicin, like most chemotherapeutics, is designed to target such cells, leaving the gastrointestinal tract open to its effects. Vomiting, nausea, inappetence, and diarrhea are among the gastrointestinal side effects associated with doxorubicin administration. They usually occur anywhere from 2 to 5 days after administration. The addition of maropitant (Cerenia; zoetis.com) to the ancillary medications
TABLE 1 Gastrointestinal Adverse Events Associated With Chemotherapy GRADE
Adverse Event
I
II
III
IV
V
Neutropenia
1500 uL to <LLN
1000–1499 uL
500–999 uL
<500 uL
Death
Anorexia: Disorder characterized by loss of appetite
Coaxing or dietary change required to maintain appetite
Oral intake altered (≤3 days) without significant weight loss; oral nutritional supplements/appetite stimulants may be indicated
Of >3 days’ duration; associated with significant weight loss (≥10%) or malnutrition; IV fluids, tube feeding, or force feeding indicated
Life-threatening consequences; TPN indicated; >5 days’ duration
Death
Diarrhea: Disorder characterized by frequent, watery bowel movements
Increase of up to 2 stools per day over baseline; no increase in frequency; however, consistency decreased over baseline
Increase of 3–6 stools per day over baseline; medications indicated; parenteral (IV or SC) fluids indicated ≤48 h; not interfering with ADL
Increase of >6 stools per day over baseline; incontinence >48 h; IV fluids >48 h; hospitalization; interfering with ADL
Life-threatening (eg, hemodynamic collapse)
Death
Nausea/ptyalism: Disorder characterized by hypersalivation and sensation or urge to vomit; difficult to assess in companion species
Loss of appetite without alteration in eating habits
Salivation or lip smacking <3 days’ duration, grade 2 anorexia
Salivation or lip smacking >3–5 days’ duration, grade 3 anorexia
Salivation or lip smacking >5 days’ duration, grade 4 anorexia
Vomiting: Disorder characterized by the reflexive act of ejecting the contents of the stomach through the mouth
<3 episodes in 24 h; medical intervention not indicated
3–10 episodes in 24 h; <5 episodes/day for ≤48 h; parenteral fluids (IV or SC) indicated ≤48 h; medications indicated
Multiple episodes >48 h and IV fluids or PPN/TPN indicated >48 h
Life-threatening (eg, hemodynamic collapse)
—
Death
ADL, activities of daily living (eating, sleeping, urinating, defecating); LLN, lower limit of normal; PPN, partial parenteral nutrition; TPN, total parenteral nutrition. Adapted with permission from Veterinary Cooperative Oncology Group—common terminology criteria for adverse events (VCOG-CTCAE) following chemotherapy or biological antineoplastic therapy in dogs and cats v1.1. Vet Comp Oncol doi: 10.1111/j.1476-5829.2011.00283.x.
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Doxorubicin in the Treatment of Specific Cancers Doxorubicin is what some might refer to as the “broad-spectrum” chemotherapy drug of choice in veterinary oncology. It has potential antagonistic properties against 3 broad categories of tumors: round cell tumors, mesenchymal tumors, and epithelial tumors. Within these categories fall some of the most common canine and feline malignancies, including lymphoma, hemangiosarcoma, and mammary gland carcinoma. Doxorubicin provides a clinical benefit in each of these types of cancer. LYMPHOMA Canine high-grade lymphoma is one of the most treatable cancers in veterinary oncology. The most common presentation is the multicentric form, which is characterized by the presence of superficial lymphadenopathy. Although lymphoma is seen often, the treatment has not made many advances in recent years. One thing that has stayed the same is that doxorubicin is the most effective drug against high-grade lymphoma when used in a single-agent protocol. This is most significant for dogs that have B-cell lymphoma. A singleagent chemotherapy protocol uses one drug in a regimen given over a certain amount of time. In this case, doxorubicin is administered every 14 to 21 days to patients for a total of 5 or 6 treatments (10–18 weeks). When this protocol is used, median patient survival times can reach 7 to 9 months, and 70% of patients go into clinical remission.1 Single-agent protocols, although effective, do not produce the high response rates of more aggressive therapy, such as multiagent chemotherapy protocols. Of the many multiagent protocols for lymphoma, the most popular is called CHOP, which is an acronym for cyclophosphamide, hydroxydaunorubicin (doxorubicin), Oncovin (vincristine), and prednisone. It has many variations. Multiagent chemotherapy protocols can induce remission in 80% to 95% of cases of high-grade canine lymphoma, with median survival times of 10 to 12 months. Of those patients, 20% to 25% will be alive 2 years after initiation of chemotherapy.2 Most multiagent chemotherapy protocols comprise weekly to biweekly chemotherapy treatments for an average of 16 to 20 weeks. Feline lymphoma has multiple presentations, the most common being nasal and gastrointestinal
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lymphoma (high or low grade). Other forms of lymphoma in cats include mediastinal, peripheral nodal, renal, and laryngeal. Unlike in dogs, singleagent doxorubicin has not proven to be a successful treatment for feline lymphoma. This fact, in addition to the potential for renal toxicity, makes multiagent chemotherapy, with the same cycle of drugs as that used in canine patients, the gold standard for feline lymphoma. Unfortunately, most forms of feline lymphoma do not have the same response rates and remission times as canine lymphoma. Cats with high-grade gastrointestinal lymphoma that receive the multiagent chemotherapy protocol can achieve remission rates of 50% to 80% and median survival times of 6 to 9 months.3 MESENCHYMAL TUMORS Mesenchymal tumors, such as hemangiosarcoma, osteosarcoma, and high-grade soft tissue sarcomas, are very aggressive and highly metastatic tumors in dogs. The treatment of choice for these types of tumors is always to control and diminish the amount of local disease. Aggressive surgeries such as splenectomy, amputation, and aggressive mass resection are the best approaches. However, once a patient’s tumor burden is reduced to microscopic disease, doxorubicin chemotherapy can be initiated. Doxorubicin is most effective for treatment of mesenchymal tumors when the tumor burden is at a microscopic level. Left untreated, tumors eventually outgrow their natural blood supply. As a result, the center of the tumor often becomes hypoxic, inhibiting the ability for cytotoxic drugs, such as doxorubicin, to reach these neoplastic cells. Cytotoxic drugs may, however, have some shortlived effects against the outermost tumor cells. If a surgical site is not quite healed, doxorubicin can still be safely administered as long as the site is clean and healthy. Doxorubicin itself does not delay wound healing, but the myelosuppressive side effects of doxorubicin could delay an immune response if an infection occurs. Single-agent doxorubicin protocols used against mesenchymal tumors are similar to those for lymphoma. Although mesenchymal tumor types are in a single class of malignancies, their disease processes and outcomes are very different.
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Hemangiosarcoma Hemangiosarcomas, tumors arising from lining of blood vessels, account for 12% to 21% of all canine mesenchymal neoplasms.4 The most common site of origin is the spleen, although they also arise in the right atrium, skin and subcutis, and liver.4 Most patients present with lethargy, decreased appetite, distended abdomen, and collapse and are likely experiencing blood loss due to a ruptured splenic tumor. However, not all bleeding splenic tumors are malignant. Approximately two-thirds of dogs with splenic masses have a malignant tumor, and approximately two-thirds of those tumors are hemangiosarcoma (the “double two-thirds rule”). Although surgery is the first step in treating splenic hemangiosarcoma, survival times with surgery alone only reach 1 to 3 months. Chemotherapy is recommended as a follow-up treatment for microscopic disease. Single-agent doxorubicin (30 mg/m2 IV every 2–3 weeks) has been shown to increase survival times to 5 to 6 months.5 Osteosarcoma Canine osteosarcoma is the most common type of primary bone tumor, accounting for >85% of skeletal tumors. Amputation should be considered palliative care only for patients with osteosarcoma of the axial skeleton. This procedure removes the source of pain, but does not address the high metastatic rates. Pulmonary metastases are found on presurgical radiographs in approximately 10% of patients, but because lesions must be 4 to 6 mm in diameter to be visible on radiographs, it is thought that most patients have micrometastases at the time of surgery. Chemotherapy is therefore recommended after amputation.6 Protocols containing platinum drugs, such as carboplatin, are considered front-line therapy, giving patients median survival times of 9 to 12 months with minimal adverse effects (250–300 mg/m2 IV every 3 weeks for 4–6 treatments7), but single-agent doxorubicin has been shown to have some cytotoxic effect against canine osteosarcoma. In one study,8 the best responses to doxorubicin were seen when it is administered every 2 weeks at 30 mg/m2, with 2 to 3 doses administered before amputation and the remaining 3 to
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4 doses afterward. Median survival times of patients in this study were just over 1 year, with about 50% of patients alive at 1 year after diagnosis, and just under 10% alive at 2 years. Soft Tissue Sarcoma Soft tissue sarcoma (STS) is a broad category of malignancies in dogs and cats, comprising 15% of all dermal tumors and 7% of all subcutaneous tumors in these species.9 STS may be classified as high grade or low grade. Low-grade STS are locally invasive tumors with low metastatic rates. These tumors can be cured with aggressive surgery with or without radiation therapy. High-grade STS are locally invasive, with metastatic rates that can reach 44%.10,11 Doxorubicin and ifosfamide are used for human STS, but response rates only reach 30%, and single-agent and multiagent protocols have not shown a significant increase in overall survival times compared to surgery alone. They do, however, help improve disease-free survival times. The role of adjuvant chemotherapy after surgery for high-grade STS in dogs is yet to be determined, but as with any high-grade tumor with high metastatic rates, it should be considered. EPITHELIAL TUMORS Doxorubicin is considered in the treatment of epithelial tumors such as mammary gland carcinoma. Mammary gland tumors are one of the most common neoplasms in sexually intact female dogs, but the incidence rate in the United States is lower than many other countries, likely due to our early ovariohysterectomy practices.12 As for most solid tumors, surgery is the first recommendation for tumor control. Many oncologists make their decisions on the need for follow-up chemotherapy based on tumor size, grade, and the presence or absence of lymphatic invasion/lymph node involvement. Studies have yet to show a clear survival or disease-free benefit from incorporating doxorubicin chemotherapy in the treatment of patients with large or multiple high-grade tumors with lymph node or pulmonary metastases. However, veterinary oncology often refers to the treatment of women with advanced or metastatic breast cancer with doxorubicin-based protocols.
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regimen after doxorubicin administration has been shown to decrease the number of patients that experience vomiting and diarrhea, and to lessen the severity of these effects in patients that do experience them.22 Patients in this study received maropitant (2 mg/kg) orally for 5 consecutive days after doxorubicin administration. Alternatively, maropitant can be given orally or subcutaneously before doxorubicin administration, followed by 4 consecutive daily doses at home. This is simpler because of the way maropitant is packaged. Fasting patients before treatment with doxorubicin has also been shown to reduce the incidence of vomiting after treatment.23 Diarrhea is another known adverse effect of doxorubicin that can manifest in the first week after administration. Metronidazole can be used to help these patients at doses as low as 10 mg/kg PO every 12 hours as needed for soft stool or diarrhea.19 If soft stool or diarrhea does not respond to metronidazole therapy, alternative options include tylosin and probiotics. Veterinary oncology technicians should be well versed in adverse gastrointestinal effects and recommended therapy so that they can accurately discuss these details with owners. Hematologic Doxorubicin’s myelosuppressive effects, which are described as mild to moderate, are one of its many dose-limiting toxicities; the established dose of doxorubicin is based on the increased rate of myelosuppression at higher doses. A complete blood cell count with differentials should be performed 7 to 10 days after doxorubicin administration to monitor for white blood cell (specifically neutrophil) nadirs. The nadir is defined as the anticipated lowest cell count in a patient after chemotherapy. Neutropenia after doxorubicin administration can be dangerous because of the potential for simultaneous adverse gastrointestinal effects. Vomiting and/or diarrhea can cause translocation of bacteria, and if a patient’s immune response is compromised, sepsis may occur.17 Other, less common hematologic effects of doxorubicin include anemia and thrombocytopenia.
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Prophylactic antibiotics may be considered after a patient’s first dose of doxorubicin. In dogs, sulfamethoxazole–trimethoprim is a broad-spectrum, cost-effective, relatively safe antibiotic that is gentle on the gastrointestinal tract. It can be started 3 days after doxorubicin infusion and continued for 7 days, or longer as needed (15–30 mg/kg PO BID).19 Doxorubicinassociated neutropenia is less common in cats, and client administration of oral medications to cats can decrease quality of life for both client and patient, so a prophylactic antibiotic can be spared in feline patients. Other Most veterinary patients do not experience the same chemotherapy-induced alopecia as human patients, but patchy alopecia may be seen in breeds with continually growing hair (eg, Maltese, golden retrievers, poodles). It mostly affects the hair around the muzzle and eyes, but severe cases of hair loss can occur (FIGURE 2). To help prevent painful
FIGURE 2. A bichon showing the extreme effects of doxorubicin-induced alopecia.
T ECHP O I N T
Peer Reviewed
Although doxorubicin poses significant risks in administration and toxicity, it is one of the most effective chemotherapeutic agents in veterinary medicine.
CONTINUING EDUCATION
if certain chemotherapeutic agents are administered shortly after radiation therapy is completed. Cases of RRD have been reported up to 2 decades after radiation therapy.24 This phenomenon is not reported in veterinary patients, but many believe it can occur. CONCLUSION Although doxorubicin poses significant risks in administration and toxicity, it is one of the most effective chemotherapeutic agents in veterinary medicine. Its effects help patients achieve lengthy and good quality of life remission and survival times for many types of malignancies. Doxorubicin’s potential benefits almost always outweigh the risks of its adverse effects. Doxorubicin is a drug that requires meticulous attention to detail and exceptional technical skills. Staff members handling doxorubicin should be well versed in
matting of the fur, it is recommended to keep patients undergoing chemotherapy well groomed. Hyperpigmentation of the skin of shaved and thinly haired areas can occur (FIGURE 3). Radiation recall dermatitis (RRD) is a phenomenon in humans in which the dermal side effects of radiation return
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FIGURE 3. A golden retriever showing the expected alopecia and hyperpigmentation effects of doxorubicin administration.
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PENN FOSTER COLLEGE, ADMINISTRATIVE OFFICE 14300 N. Northsight Blvd., Scottsdale, AZ 85260 PENN FOSTER CAREER SCHOOL 925 Oak Street, Scranton, PA 18515
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Doxorubicin: An Overview PEER REVIEWED
in the potential adverse effects to be able to comfort and educate owners of pets going through chemotherapy. Caution Federal (USA) law restricts this drug to use by or on the order of a licensed veterinarian.
References 1. Postorino NC, Susaneck SJ, Withrow SJ, et al. Single agent therapy with adriamycin for canine lymphosarcoma. JAAHA 1989;25:221. 2. Vail DM. Hematopoietic tumors. In: Ettinger SJ, Feldman EC, eds. Textbook of Veterinary Internal Medicine. 6th ed. St. Louis, MO: Elsevier; 2005. 3. Milner RJ, Peyton J, Cooke K, et al. Response rates and survival times for cats with lymphoma treated with the University of Wisconsin-Madison chemotherapy protocol: 38 cases (1996-2003). JAVMA 2005;227(7):118-122. 4. MacVean DW, Monlux AW, Anderson PS, et al. Frequency of canine and feline tumors in a defined population. Vet Pathol 1978;145:700-715. 5. Ogilvie GK, Powers BE, Mallinckrodt CH, et al. Surgery and doxorubicin in dogs with hemangiosarcoma. J Vet Intern Med 1996;10:379-384. 6. Withrow SJ, Vail DM, Page RL. Cancer chemotherapy. In: Small Animal Clinical Oncology. 5th ed. St. Louis: Elsevier Saunders; 2013:157-173. 7. Bergman PJ, MacEwen EG, Kurzman ID, et al. Amputation and carboplatin for treatment of dogs with osteosarcoma: 48 cases (1991 to 1993). J Vet Intern Med 1996;10(2):76-81. 8. Berg J, Weinstein MJ, Springfield DS, Rand WM. Results of surgery and doxorubicin chemotherapy in dogs with osteosarcoma. JAVMA 1995;206(10):1555-1560. 9. Theilen GH, Madewell BR. Tumors of the skin and subcutaneous tissues. In: Theilen GH, Madewell BR, eds. Veterinary Cancer Medicine. Philadelphia, PA: Lea & Febiger; 1979. 10. Kuntz CA, Dernell WS, Powers BE, et al. Prognostic factors for surgical treatment of soft-tissue sarcomas in dogs: 75 cases (1986-1996). JAVMA 1997;21:1147-1151. 11. Selting KA, Powers BE, Thompson LJ, et al. Outcome of dogs with highgrade soft tissue sarcomas treated with and without adjuvant doxorubicin chemotherapy: 39 cases (1996-2004). JAVMA 2005;227:1442-1448. 12. Moe L. Population-based incidence of mammary tumours in some dog breeds. J Reprod Fertil Suppl 2001;57:429-443. 13. Tan C, Tasake H, Yu K, et al. Daunomycin, an antitumor antibiotic, in the treatment of neoplastic disease. Cancer 1967;20(3):333-353. 14. Young RC, Ozols RF, Myers CE. The anthracycline antineoplastic drugs. N Engl J Med. 1981;305(3):139-153. 15. Eschalier A, Lavarenne J, Burtin C, et al. Study of histamine release induced by acute administration of antitumor agents in dogs. Cancer Chemother Pharmacol 1988;21:246-250. 16. O’Keefe DA, Sisson DD, Gelberg HB, et al. Systemic toxicity associated with doxorubicin administration in cats. J Vet Intern Med 1993;7(5):309-317. 17. Thamm DH, Vail DM. Aftershocks of cancer chemotherapy: managing adverse events. JAAHA 2007;43(1):1-7. 18. Pharmacia & Upjohn. Dexrazoxane [package insert]. New York; 2012. 19. Plumb DC. Plumb’s Veterinary Drug Handbook. 8th ed. Stockholm: PharmaVet Inc; 2015:1345-1349. 20. Venable R, Saba C, Endicott M, Northrup N. Dexrazoxane treatment of doxorubicin extravasation injury in four dogs. JAVMA 2012;240(3):304-307. 21. Veterinary cooperative oncology group—common terminology criteria for adverse events (VCOG-CTCAE) following chemotherapy or biological antineoplastic therapy in dogs and cats v1.1. Vet Comp Oncol 2011. doi: 10.1111/j.1476-5829.2011.00283.x. 22. Rau SE, Barber LG, Burgess KE. Efficacy of maropitant in the prevention of delayed vomiting associated with administration of doxorubicin to dogs. J Vet Intern Med 2012;24(6):1452-1457 23. Withers SS, Hass PH, Rodriguez CO, et al. Fasting reduces the incidence of delayed-type vomiting associated with doxorubicin treatment in dogs with lymphoma. Transl Oncol 2014;7(3):377-383. 24. Haas RLM, Klerk G. An illustrated case of doxorubicin-induced radiation recall dermatitis and a review of the literature. Neth J Med 2011;69(2):72-75.
Indications SENTINEL® SPECTRUM® (milbemycin oxime/lufenuron/praziquantel) is indicated for the prevention of heartworm disease caused by Dirofilaria immitis; for the prevention and control of flea populations (Ctenocephalides felis); and for the treatment and control of adult roundworm (Toxocara canis, Toxascaris leonina), adult hookworm (Ancylostoma caninum), adult whipworm (Trichuris vulpis), and adult tapeworm (Taenia pisiformis, Echinococcus multilocularis and Echinococcus granulosus) infections in dogs and puppies two pounds of body weight or greater and six weeks of age and older. Dosage and Administration SENTINEL SPECTRUM should be administered orally, once every month, at the minimum dosage of 0.23 mg/lb (0.5 mg/kg) milbemycin oxime, 4.55 mg/lb (10 mg/kg) lufenuron, and 2.28 mg/lb (5 mg/kg) praziquantel. For heartworm prevention, give once monthly for at least 6 months after exposure to mosquitoes.
Dosage Schedule Praziquantel per Number of chewable chewables
Milbemycin Oxime per chewable
Lufenuron per chewable
2 to 8 lbs.
2.3 mg
46 mg
22.8 mg
One
8.1 to 25 lbs.
5.75 mg
115 mg
57 mg
One
25.1 to 50 lbs.
11.5 mg
230 mg
114 mg
One
50.1 to 100 lbs.
23.0 mg
460 mg
228 mg
One
Body Weight
Over 100 lbs.
Administer the appropriate combination of chewables
To ensure adequate absorption, always administer SENTINEL SPECTRUM to dogs immediately after or in conjunction with a normal meal. SENTINEL SPECTRUM may be offered to the dog by hand or added to a small amount of dog food. The chewables should be administered in a manner that encourages the dog to chew, rather than to swallow without chewing. Chewables may be broken into pieces and fed to dogs that normally swallow treats whole. Care should be taken that the dog consumes the complete dose, and treated animals should be observed a few minutes after administration to ensure that no part of the dose is lost or rejected. If it is suspected that any of the dose has been lost, redosing is recommended. Contraindications There are no known contraindications to the use of SENTINEL SPECTRUM. Warnings Not for use in humans. Keep this and all drugs out of the reach of children. Precautions Treatment with fewer than 6 monthly doses after the last exposure to mosquitoes may not provide complete heartworm prevention. Prior to administration of SENTINEL SPECTRUM, dogs should be tested for existing heartworm infections. At the discretion of the veterinarian, infected dogs should be treated to remove adult heartworms. SENTINEL SPECTRUM is not effective against adult D. immitis. Mild, transient hypersensitivity reactions, such as labored breathing, vomiting, hypersalivation, and lethargy, have been noted in some dogs treated with milbemycin oxime carrying a high number of circulating microfilariae. These reactions are presumably caused by release of protein from dead or dying microfilariae. Do not use in puppies less than six weeks of age. Do not use in dogs or puppies less than two pounds of body weight. The safety of SENTINEL SPECTRUM has not been evaluated in dogs used for breeding or in lactating females. Studies have been performed with milbemycin oxime and lufenuron alone. Adverse Reactions The following adverse reactions have been reported in dogs after administration of milbemycin oxime, lufenuron, or praziquantel: vomiting, depression/lethargy, pruritus, urticaria, diarrhea, anorexia, skin congestion, ataxia, convulsions, salivation, and weakness. To report suspected adverse drug events, contact Virbac at 1-800-338-3659 or the FDA at 1-888-FDA-VETS. Information for Owner or Person Treating Animal Echinococcus multilocularis and Echinococcus granulosus are tapeworms found in wild canids and domestic dogs. E. multilocularis and E. granulosus can infect humans and cause serious disease (alveolar hydatid disease and hydatid disease, respectively). Owners of dogs living in areas where E. multilocularis or E. granulosus are endemic should be instructed on how to minimize their risk of exposure to these parasites, as well as their dog’s risk of exposure. Although SENTINEL SPECTRUM was 100% effective in laboratory studies in dogs against E. multilocularis and E. granulosus, no studies have been conducted to show that the use of this product will decrease the incidence of alveolar hydatid disease or hydatid disease in humans. Because the prepatent period for E. multilocularis may be as short as 26 days, dogs treated at the labeled monthly intervals may become reinfected and shed eggs between treatments. Manufactured for: Virbac AH, Inc. P.O. Box 162059, Ft. Worth, TX 76161 NADA #141-333, Approved by FDA © 2015 Virbac Corporation. All Rights Reserved. SENTINEL and SPECTRUM are registered trademarks of Virbac Corporation. 02/15
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Important Safety Information for SENTINEL® SPECTRUM® (milbemycin oxime/lufenuron/praziquantel): Dogs should be tested for heartworm prior to use. Mild hypersensitivity reactions have been noted in some dogs carrying a high number of circulating microfilariae. Treatment with fewer than 6 monthly doses after the last exposure to mosquitoes may not provide complete heartworm prevention. Please see full product label for more information, or visit us.virbac.com. Reference: 1. Data on file, Vetstreet Data Analytics. Virbac Corporation.
© 2017 Virbac Corporation. All Rights Reserved. SENTINEL and SPECTRUM are registered trademarks of Virbac Corporation. 5/17 17294
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M E E T T H E AU T H O R
Feline Heartworm Disease: Fact or Fiction?
Ann Wortinger, BIS, LVT, VTS (ECC, SAIM, Nutrition) Belleville, Michigan
shutterstock.com/WaitForLight
The mosquito-borne parasite Dirofilaria immitis is known to infect multiple species, including dogs, cats, ferrets, wolves, coyotes, foxes, sea lions, and even humans.1 Canids, including dogs, are the definitive hosts, while cats are viewed as aberrant or atypical hosts.1 Unlike dogs, in North and South America, D immitis is the only filarial disease that infects cats.2 Heartworm disease was first reported in cats in Brazil in 1921, yet some still believe that cats cannot be infected with D immitis.2 A 2007 study demonstrated that when dogs that were not administered a heartworm preventive were artificially infected with 100 L3 larvae, approximately 75% of the larvae developed into adult heartworms in every dog. When cats that were not administered heartworm preventive were artificially infected with 100 L3 larvae, 3 to 10 adult worms were found in 75% of the cats.2 This study demonstrated that cats can be successfully infected with heartworms.2
Ann is a 1983 graduate of Michigan State University. She has worked in general, emergency, and specialty practice, as well as education and management. Ann is active in her state, national, and specialty organizations and served on the organizing committees for the internal medicine and nutrition veterinary technician specialties. She has mentored over 15 fellow veterinary technician specialists. She has published more than 45 articles in professional magazines, as well as book chapters, and is a coauthor of Nutrition and Disease Management for Veterinary Technicians and Nurses, now in its second edition.
STUDIES CONDUCTED IN THE 1990s found that about 2.5% to 14% of cats in the southeastern United States were infected with heartworms.
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The death of immature heartworms in the lungs of cats may cause severe pulmonary clinical signs similar to those seen with feline asthma.
The 2007 study also demonstrated that the rate of infection and development of infective heartworm larvae into adults in cats is significantly lower than that of dogs in the same geographic area.2 Studies conducted in the 1990s found that about 2.5% to 14% of cats in the southeastern United States were infected with heartworms—numbers similar to or higher than FeLV or FIV infection rates.3 A study conducted at North Carolina State University showed that 25% of the infected cats there were considered by their owners to be strictly indoor cats,3 indicating that living indoors does not provide adequate protection from mosquito bites. In 2001, the American Heartworm Society reported more than 244,000 positive heartworm tests for dogs and 3,000 positive tests for cats. Considering the problems with testing in cats, as well as the low number of tests performed, this report is assumed to underrepresent the true incidence of the disease. The nationwide incidence in cats is estimated to be approximately 12%.3 The reliability of heartworm testing, which depends on the presence of heartworm antigen or microfilariae, is affected by the relative lack of both in cats. Because cats are aberrant hosts, the lifespan of adult heartworms is reduced in this species, resulting in a shortened period of patency. As a result, microfilariae, produced by adult female heartworms in the presence of adult male heartworms, are uncommon in cats. It is believed that some cats may be able to spontaneously rid themselves of an infection with a strong immune response.4
bite, initiating a severe inflammatory response. In cats, this response, the first active phase, has been called heartworm-associated respiratory disease, or HARD, and it is responsible for the pathology seen in the arteries of the lungs as well as the bronchioles and alveoli.1,4 If any immature worms survive this immunologic onslaught and make it to adulthood, the initial inflammatory response may recede. Phase 2 is initiated when the adult worms begin to die. In dogs, adult worms can live in the heart and lungs for more than 5 years, but in cats, the typical lifespan is less than 2 years.2 The release of new heartworm debris into the bloodstream initiates a second inflammatory response, also primarily localized in the lungs.4 Lesions in the second phase of infection are associated with dead worm fragments as the immune system removes them from the body. The only exit for parasitic debris in the bloodstream is through the action of phagocytic cells.
DISEASE PHASES If cats are able to spontaneously rid themselves of adult heartworms, should patent infections be of concern? Heartworm disease in cats can have 2 active phases. As in dogs, surviving L3 larvae molt to the L4 stage and migrate through body tissues. The immature worms arrive in the lungs between 60 and 100 days after the infected
IMMUNOLOGIC RESPONSE The severe inflammatory response to the arrival of the immature worms in the pulmonary arteries prompts the mobilization of pulmonary macrophages, which are designed to envelop and digest foreign material such as bacteria and parasites. Macrophages that behave in this manner in response to a dirofilarial infection are not present in dogs, explaining the
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difference in response in cats. However, while the feline immune system attacks the arriving worms, evidence suggests that the worms are able to suppress the immune response.2 The special macrophages are also key players in the intense inflammatory reaction to the debris created when adult heartworms die, leading to pulmonary dysfunction and HARD. This round of immunologic responses can occur with each infected bite, as well as with death of each adult worm.2,4 The death of immature heartworms in the lungs of cats may cause severe pulmonary clinical signs similar to those seen with feline asthma. These signs may appear as early as 80 to 90 days after infection, a full 3 months before adult female heartworms would begin to release antigen into the bloodstream. Because commonly used canine heartworm antigen tests identify this antigen, these tests cannot be used to confirm a diagnosis of heartworm disease during the initial disease process in cats. To further complicate diagnosis, accompanying pulmonary radiographic lesions are not specific for heartworm disease and could represent true feline asthma or other parasitic infections such as visceral larval migrans. Because of their small size (microfilariae require 40× to 100× magnification to be seen on microscopy), worms and worm fragments cannot be seen using readily available imaging techniques.2 LUNG CHANGES In addition to the inflammatory response, immature heartworms can cause embolization of pulmonary arteries. With embolization of these vessels, gas exchange is compromised or absent. Obstruction of blood flow through the lungs, especially in the caudal pulmonary arteries, causes acute respiratory signs, and the involved lung lobe becomes hemorrhagic, with local areas of edema. Signs of inflammation can be seen in lung lobes not associated with the embolization, indicating that the disease is not simply an obstructive disease (FIGURE 1). Immature worms arriving in the pulmonary vasculature can cause pulmonary arterial,
arteriolar, and airway lesions as severe as those seen with death of adult heartworms. If the cat survives the initial embolic event, recanalization around the obstruction occurs rapidly, and lung function is markedly improved within days. Median survival is 1.5 years for all infected cats and 4 years for those that survive their first 24 hours after this severe respiratory episode.3 In chronically infected cats, perivascular reactions and evidence of thrombus formation can be seen, but cardiac changes are minimal compared to those seen in dogs.2 In cats, acute lung injury caused by the death of adult worms can result in generalized respiratory failure. A significant acute inflammatory component can be seen, especially when the adult heartworms die.2 CLINICAL SIGNS AND PHYSICAL EXAMINATION FINDINGS The inflammatory response to the arrival of immature worms in the lungs may cause asthma-like signs.2 These cats may initially present with a history of coughing, dyspnea, and vomiting. Rapid and difficult breathing may be noted on examination. Additionally, the owners may note lethargy, anorexia, and weight loss. Alone, none of these signs
FIGURE 1. Lung from cat with heartworm-associated respiratory disease but no adult heartworm. Signs of inflammation include red color and rounded margins. Healthy lungs are pink with sharp margins. Image used courtesy of Zoetis
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is diagnostic for heartworm infection.2,4 Coughing is usually temporary and is initially responsive to corticosteroids. Physical examination findings are usually within normal limits, but there may be a systolic murmur over the tricuspid valve area, and occasionally a gallop rhythm is noted. Uncommonly, harsh lung sounds may be heard; these are often referred to as dry rales.2 Clinical signs and, possibly, thoracic radiographic findings are similar in cats with abbreviated heartworm infections and those with other causes of bronchial disease, such as feline asthma. An abbreviated infection can be caused by spontaneous removal of the larvae by the cat’s immune system or treatment with a preventive drug such as ivermectin or selamectin. Because of this, it is possible that HARD is underdiagnosed, particularly in geographic areas where heartworm infections are common.4 Unfortunately, one of the primary signs of adult heartworm death in cats is sudden death of the host.2 This has been attributed to circulatory collapse and respiratory failure from acute pulmonary arterial infarction and acute lung injury.2 Acute respiratory collapse may occur with or without previous clinical signs. DIAGNOSTICS Diagnostics can be a challenge in a dyspneic cat, involving a complete physical examination, thoracic radiography, cardiac ultrasonography, angiocardiography, a complete blood count, heartworm antigen/ antibody tests, and microfilaria testing.1 The specificity and sensitivity of these tests vary, and there is no one ideal test for heartworm disease in cats. Necropsy may be required in cases of sudden death.1 Radiography Even though the pulmonary parenchymal changes are nonspecific and can change rapidly in infected cats, thoracic radiography has proven to be a valuable diagnostic tool for heartworm disease and has the
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TECHPOINT
It is believed that some cats may be able to spontaneously rid themselves of an infection with a strong immune response. advantage of being available for most practitioners. Lung changes can include diffuse or coalescing infiltrates, perivascular densities, and lung atelectasis. On radiographs, enlarged pulmonary arteries are evident, with ill-defined margins. Changes are usually most prominent in the lower (caudal) lobes of the lungs (FIGURE 2).1 Ultrasonography Unlike in dogs, adult worms are seldom found in the heart in cats (FIGURE 3). Cardiac ultrasonography of adult worms in the main pulmonary artery and close portions of the right and left branches of the artery enable definitive diagnosis of heartworm disease. Parallel hyperechoic lines representing an image from the adult heartworm’s cuticle (outside
FIGURE 2. The most common radiographic findings in feline heartworm disease are enlargement of the right caudal lobar artery and a bronchointerstitial inflammatory pattern in the caudal lung lobes.3 Image used courtesy of Zoetis
todaysveterinarytechnician.com PEER REVIEWED
lining) are consistent with the presence of adult heartworms.2 With ultrasonography, it is virtually impossible to visualize the smaller pulmonary arteries where young worms are often found.1 The ability to find heartworms with ultrasonography depends on the cooperation of the patient, the skill of the ultrasonographer, and the location of the worms. Antigen Testing Unlike radiography and ultrasonography, which do not depend on the sex of the heartworm(s), antigen testing is most accurate at detecting infection with 1 or more female worms that are at least 7 to 8 months old (sexually mature). The specific antigen detected during testing is produced by the gravid adult female worm’s uterus. Antigen testing is not as effective at detecting infection with adult worms <5 months old and is unable to detect immature worm infections, male-only infections, and some infections with only one adult female worm.1 If the infection does not produce an adult worm, the worms are immature at the time of testing, or only male adult worms are present, a false-negative result may be obtained. Therefore, a positive antigen test is diagnostic for active adult heartworm infection, but a negative antigen test does not rule out infection. Most cats with heartworm disease are antigen negative because of low titers.2
FIGURE 3. Adult Dirofilaria immitis in a feline heart. In cats, usually only 1 to 3 adults are found. Image used courtesy of Zoetis
ELISA Testing Antibody testing uses an enzyme-linked immunosorbent assay (ELISA) that detects feline antibodies to heartworm antigen. These antibodies are produced in response to early migration of L3 and L4 larvae. Positive results can be detected 2 to 3 months after infection. Initial studies of cats that have naturally eliminated the adults or microfilariae show that the host antibody gradually decreases to negative concentrations after 4 to 6 months. Cats that are on a macrolide preventative (ie, selamectin, ivermectin, or moxidectin) can have a false-positive ELISA result after being bitten by an infected mosquito, with resultant larvae death and no persistent infection.2 Because antibodies are produced after the initial exposure, a positive result indicates that the cat has been bitten by a D immitis– carrying mosquito 2 to 3 months previously, but not whether it is currently infected. Use of purified recombinant heartworm antigen can increase test sensitivity for an active infection.1 The ELISA is a method of analysis, and variations in antigen preparation, antibody sources, and laboratory techniques between diagnostic labs and in-house testing kits can create variation in results.2 The death of adult heartworms and subsequent release of large amounts of antigen from decomposing fragments may produce a strong antibody response. Some of the highest titers are associated with severe clinical signs in cats after adult worms have died and the disease itself may be resolving.2 Immunofluorescence Assay Testing An immunofluorescence assay (IFA) can be used to detect cuticular antigen expressed by adult heartworms. IFAs detect approximately 33% of positive infections. They are not effective in detecting infections with immature worms, sterile worms, single-sex infections, or absence of a host response.2 Somatic IFAs, which look for antibodies to microfilarial somatic antigen, are nonspecific. IFAs have been helpful in researching the biology of parasite–host interaction but have demonstrated limited application in clinical diagnostics.2
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Blood Testing A complete blood count may show a mild anemia (hematocrit 23%â&#x20AC;&#x201C;33%) in 30% of cases, with nucleated red blood cells and rare basophils present. Approximately 30% of infected cats have elevated eosinophil counts, although this depends on the phase of the disease when the cat is tested (FIGURE 4). During the initial inflammatory phase and when adult worms are dying, the eosinophil count can be higher than during the state between these 2 phases of infection.2 Electrocardiography Electrocardiography can be useful in detecting the subtle sign of right ventricular enlargement. Ectopic ventricular beats and other arrhythmias are occasionally seen after adulticide treatment in asymptomatic cats.2 As neither of these findings is consistent with heartworm disease, this diagnostic test is likely of little value alone. Cytology Tracheal cytology may be performed on a cat that is sedated rather than under full anesthesia. The presence of eosinophils in the recovered tracheal fluid is consistent with heartworm disease, feline asthma, and parasitic lung disease. In heartworm disease, eosinophils can be found in the recovered fluid
FIGURE 4. Feline eosinophil. The presence of eosinophils is consistent with a parasitic or allergic infection but is not specific for either. Image used courtesy of Zoetis
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4 to 7 months after L3 infection; however, they may not be present later in the infection even if adult worms are present. Tracheal cytology consistent with chronic inflammation may be present after eosinophilia has resolved.2 Bronchoalveolar lavage can be performed if the cat is stable enough to be placed under anesthesia. Eosinophils may or may not be present in the lavage fluid, but the presence of basophils is highly suggestive of heartworm disease.2 Lavage is highly unlikely to retrieve larvae or adult worms, as these parasites are located within the pulmonary vessels and not within the bronchioles and alveoli. Necropsy On necropsy, the general pulmonary pathology of infected cats is similar to that of infected dogs: muscular hypertrophy of the main vessels of the lungs, villous endarteritis, and cellular infiltrates of the adventitia (the outmost layer of the blood vessels; FIGURE 5).2 Obviously, finding adult worms or fragments would be consistent with death due to lung collapse related to worm death. TREATMENT Adulticide Therapy No approved treatment for feline heartworm infection currently exists. While adulticide thiacetarsamide treatment is well tolerated by cats without immediate complications, the
FIGURE 5. Feline lungs showing consolidation and inflammation caused by heartworm-associated respiratory disease. Image used courtesy of Zoetis
VETFOLIO WORK Cristi Semmler, BS, CVT, RALAT Faculty Instructor of Veterinary Technology Eastern Wyoming College VetFolio User Since 2015
Teaches 65-70 students each semester
See how Cristi puts VetFolio to work: Signing Up “At the NAVC Conference in 2015, I chatted with one of the reps at the booth. I found out that there was no subscription fee for educators, so I looked into signing up. I liked the different types of courses available. As an educator, I like to be on the cutting edge of veterinary education so I can give students a heads-up on what’s new in the industry.” Getting Started “If I’m working on my CE, I’m usually at home. I use VetFolio to look for specific examples for my students. I’ll watch a course at home and assign it as a module in class, and ask them to bring their certificate in to show they completed it. If I tell students “This is how it is” about a certain topic, they may not take it as well from me, but coming from expert in the field, it really has weight. We frequently use VetFolio courses to enhance the information in class.” Becoming a Pro Pro tip: “Go into specific continuing education and search for something you’re interested in. You may need to generalize your search term a little to find what you’re looking for. I probably spent 30 hours over the Christmas 2015 break doing continuing education just because I felt like it.” “I think the Certificate Course series are great for students to take and put on their resumes. I think it makes them look more knowledgeable in the eyes of potential employers.”
Photo credit: Sunshine Photography by Corrie Gamel
Meet Azule! Institutional Animal Care and Use Committee Chair
Finding Her Passion • Pain management • Lab research • Educating future generations Making #Goals Completing the six-course series on veterinary forensic science & medicine and animal crime scene investigation
INDIVIDUAL AND PRACTICE SUBSCRIPTIONS AVAILABLE. SEE HOW VETFOLIO CAN WORK FOR YOU AT VETFOLIO.COM.
Feline Heartworm Disease: Fact or Fiction? PEER REVIEWED
arrival of dead worms and worm fragments in the pulmonary vasculature causes an immunologic response that results in significant pulmonary edema within 2 days of the initial injection. Death as a result of respiratory collapse may ensue. Pulmonary edema may be responsive to oxygen therapy and high-dose corticosteroid treatment.2 The routine use of corticosteroids is not recommended before or after thiacetarsamide treatment, and aspirin is contraindicated in feline heartworm disease. Sudden death due to embolization can occur after adulticide treatment, especially within the first 10 days after administration. Embolization can also induce severe lung injury, hemoptysis, and dyspnea. The advantage to treating a cat with an adulticide is being able to observe it during the 2-week period after treatment while the worms are dying, compared to not knowing when the heartworms will die naturally in an untreated cat.2 Immature larvae are thought to be resistant to thiacetarsamide, meaning that any developing heartworm larvae present at the time of treatment will not be killed. If any of these larvae subsequently develop into adult worms, the cat may have a second adult infection.2 Ivermectin treatment is successful in removal of microfilariae, but does not kill adult worms, although the remaining female worms may become sterile. Canine doses of Immiticide should not be used in cats.2 Conservative Therapy In light of the significant risks associated with adulticide treatment, many owners opt for conservative therapy for heartworm-infected cats. This does not eliminate the chance of embolization, but it can help manage the signs of respiratory distress and dyspnea. Alternateday prednisolone therapy has been successfully used to help manage clinical signs of coughing and vomiting. It has no effect on progression of lesions in the lungs, as evidenced by radiography.2 An emergency dose of an oral or injectable glucocorticoid should be given to the owner in the event of a severe episode of
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TECHPOINT
Ivermectin treatment is successful in removing microfilariae but does not kill adult worms, although the remaining female worms may become sterile.
collapse or dyspnea, to allow them time to get the cat to an emergency facility for additional treatment. As this therapy addresses only the inflammatory response, not the vascular trauma or the presence of migrating larvae or surviving adults, the chance of acute death is still present. In the event of respiratory distress or collapse, emergency treatment involving oxygen therapy, cage rest, small volumes of IV fluids, and injectable prednisolone can result in clinical improvement and resolution of clinical signs within 24 hours. PREVENTION Feline heartworm disease is challenging to diagnose and has no approved, effective, or safe treatment, but highly effective preventives are available: Heartgard (merial.com), containing the active ingredient ivermectin, Revolution (zoetis.com), containing the active ingredient selamectin, and Advantage Multi (bayerdvm.com), containing the active ingredient moxidectin, are all approved for prevention of heartworm in cats. Heartgard is available as an oral chew and is administered once monthly. Revolution and Advantage Multi are topical medications that are applied to the skin, also once monthly. Both ivermectin and selamectin can be given to kittens as young as 6 weeks of age and continued for the life of the cat. Moxidectin should not be applied to kittens younger than 9 weeks of age. Because mosquitoes can be found indoors,
todaysveterinarytechnician.com PEER REVIEWED
current recommendations are to administer these medications year-round in endemic areas. Since current antigen testing is inconsistent in cats, especially those with low worm counts, it is not recommended to test asymptomatic adult cats before administering preventive therapy. For cats with subclinical signs of heartworm infection, progression to obvious signs of allergic lung disease can be seen after preventive administration. Despite this, heartworm-positive cats can be safely placed on preventive medications, which will help prevent another round of infection. CONCLUSION In areas where dogs are exposed to mosquitoes that carry D immitis, so are cats. Although heartworm disease in cats can be self-limiting, with a small number of cats able to spontaneously rid themselves of adult worms, migrating larvae damage
the lungs and vasculature before clinical signs appear. In some cats, the first sign of infection is acute respiratory collapse and death, which can be devastating to owners. Even if you do not see heartworm-positive cats in your practice, rest assured that they are seeing you every week. Fortunately, effective preventives exist. By educating clients about the facts of HARD, veterinary technicians can help improve feline health! ď Ž References 1. American Heartworm Society. Heartworm in cats. heartwormsociety.org/heartwormsin-cats. Accessed June 2016. 2. Blagburn B, Dillon R. Feline heartworm disease: solving the puzzle. veterinarymedicine.dvm360.com/felineheartworm-disease-solving-puzzle. Accessed June 2016. 3. Atkins CE. Are we doing enough to prevent heartworm infections? capcvet.org/expert-articles/are-we-doing-enoughto-prevent-heartworm-infections/. Accessed June 2016. 4. Cornell University College of Veterinary Medicine, Cornell Feline Health Center. Heartworm in cats. vet.cornell.edu/fhc/Health_Information/ Heartworm.cfm. Accessed June 2016.
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CLIENT HANDOUT
Heartworm Disease in Cats Heartworm disease attacks the lungs, heart, and related blood vessels. It is serious and potentially fatal. Heartworms are transmitted through the bite of an infected mosquito. There is no approved treatment for heartworm disease in cats. Illness is easily and effectively avoided by giving preventive medications.
What Is Heartworm Disease? Heartworm disease is a serious and potentially fatal condition that affects dogs, cats, and up to 30 other species of animals. It is caused by parasitic worms (heartworms) living in the major blood vessels of the lungs and, occasionally, in the heart. These worms are transmitted (as microscopic larvae) through the bite of an infected mosquito. The scientific name for the heartworm parasite is Dirofilaria immitis.
Despite the fact that heartworm disease is virtually 100% preventable, many cats are diagnosed with it each year. However, diagnosis is more difficult in cats than in dogs, so it is likely that many cats have heartworm disease that is not recognized. Although cats are considered resistant to heartworms and sometimes can fight off an infection on their own, heartworm disease can still be a serious health problem for cats, resulting in significant illness and even
shutterstock.com/HealthHappy HH
Despite the fact that heartworm disease is virtually 100% preventable, many cats are diagnosed with it each year.
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Heartworm Disease in Cats continued death. Keeping a cat indoors does not prevent infection. Multiple studies have shown that more than 25% of heartworm-infected cats live indoors. The American Heartworm Society (AHS) estimates that one million dogs in the United States have heartworm disease today, and this number may be rising. Wherever dogs are infected, studies have shown that cats are likely to be infected, too.
Diagnosis Heartworms are spread through the bite of a mosquito, and dogs serve as the source of infection for other dogs and for cats. When a mosquito bites an infected dog, it withdraws blood that contains immature heartworms (called microfilariae [pronounced micro-fill-air-ee-ay]). These microfilariae mature inside the mosquito to become infective larvae. When the mosquito eventually bites another dog or a cat, the larvae enter the new host. In dogs, these larvae often mature to become adult heartworms, which produce more microfilariae and continue the heartworm’s life cycle. The life cycle of heartworms in cats is slightly different from the life cycle in dogs. For example, many heartworms die during development in a cat, so they don’t live long enough to produce microfilariae. Additionally, the immune system of some cats can eliminate the heartworm infection before the worms reach adulthood. For these reasons, heartworm testing in cats is more complicated than the process in dogs. Many types of tests conducted on different occasions may be necessary. Negative test results do not necessarily rule out heartworm infection,
and positive results (depending on the test) do not always confirm infection. Many veterinarians use heartworm antigen and/or antibody tests to begin the screening process for heartworm disease in cats. Each of these tests has strengths and limitations, and neither test will, by itself, identify heartworm disease in all infected cats: Antibody testing: “Antibodies” are specific proteins that the body produces in response to invasion by a foreign organism. Heartworm antibody tests detect antibodies produced by a cat in response to the presence of developing heartworms (heartworm larvae). A positive result on an antibody test could indicate an early infection or a previous infection (that the cat’s immune system already eliminated), but not necessarily a current one. In fact, many antibody-positive cats do not have adult heartworms. Additionally, some cats with heartworms don’t produce antibodies the whole time they are infected, so a cat that has a mature (adult) infection may actually test negative on an antibody test. Antigen testing: “Antigens” are proteins that the body can recognize as belonging to a foreign organism. By identifying certain antigens that are found in adult female heartworms, researchers have developed tests that can detect these antigens to tell if a cat is infected with adult heartworms. Many veterinarians use a rapid-result test called a “SNAP” test to begin diagnosing heartworm disease in cats. The SNAP test is very accurate, can be performed in your veterinarian’s office using a very small amount of
Signs of Heartworm Disease Cats usually have fewer heartworms than dogs, and the worms may not grow as big. However, because cats are generally smaller than dogs and have smaller blood vessels, the presence of even a few worms can cause lung damage. Some cats with heartworm disease never show any signs. When present, the signs of heartworm infection in cats can be confused with signs of many other diseases, including feline asthma. Affected cats may vomit, cough, and have difficulty breathing. This condition is called heartworm-associated respiratory disease (HARD). Sometimes, the only sign of infection is sudden death.
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Heartworm Disease in Cats continued
blood, and takes only a few minutes to complete. There is even a combination SNAP test that can detect heartworm disease as well as feline leukemia virus (FeLV) and feline immunodeficiency virus (FIV) at the same time. The feline heartworm antigen test only identifies the antigen associated with adult female heartworms. Therefore, it will not detect an infection when only larvae are present or when only adult male heartworms are present. If your veterinarian obtains a questionable result on the SNAP test, additional testing may be recommended.
Keeping a cat indoors does not prevent infection. Multiple studies have shown that more than 25% of heartworm-infected cats live indoors.
Some veterinarians use an outside laboratory to perform feline heartworm antibody and/or antigen testing. In these cases, results are generally available within a few days. Diagnosis of feline heartworm disease may involve other types of diagnostic tests besides blood
work. Sometimes, evidence of heartworms can be seen on ultrasound images or radiographs (“x-rays”) of the heart and lungs. Unfortunately, these tests can also be inconclusive.
Treatment In cats, there is no real treatment for heartworm disease itself. Your veterinarian will determine how to monitor your pet and manage the signs of disease. In some cases, surgical removal of the worms may be recommended. However, this surgery is costly and has some risks.
Prevention Safe, easy-to-give, effective medications are available to prevent heartworm disease. These monthly oral or topical (“spot on”) medications are inexpensive compared with the dangers of the disease for your cat. Ask your veterinarian which method and schedule of heartworm prevention are best for you and your pet.
© 2017 Today’s Veterinary Technician. Created by Vetstreet and peer-reviewed by Today’s Veterinary Technician. Brought to you by VetFolio. Today’s Veterinary Technician grants permission to individual veterinary clinics to copy and distribute this handout for the purposes of client education. For a downloadable PDF, please visit www.todaysveterinarytechnician.com.
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Clients want to fight fleas and ticks – not their dogs. Protect dogs with the beefflavored chew they love.1
Data on file at Merial.
1
®NexGard is a registered trademark, and TM FRONTLINE VET LABS is a trademark, of Merial. ©2016 Merial, Inc., Duluth, GA. All rights reserved. NEX16TRADEADS3 (01/17).
IMPORTANT SAFETY INFORMATION: NexGard® is for use in dogs only. The most frequently reported adverse reactions included pruritus, vomiting, dry/flaky skin, diarrhea, lethargy, and lack of appetite. The safe use of NexGard in pregnant, breeding, or lactating dogs has not been evaluated. Use with caution in dogs with a history of seizures. For more information, see full prescribing information or visit www.NexGardForDogs.com.
Trazodone in Veterinary Medicine TOXICOLOGY TALK
TOXICOLOGY TALK MEET THE AU TH O R
Tamara Foss, CVT ASPCA Animal Poison Control Center Urbana, Illinois Tamara has been with the ASPCA Animal Poison Control Center since 2000. She earned her bachelor’s degree in agriculture with an emphasis in animal health technology from Murray State University in Kentucky. Tamara especially enjoys the toxicology-, research-, and information technology–related aspects of her position at the ASPCA. She has a passion for greyhounds and is an active volunteer and foster for American Greyhound. Outside of work, she loves spending time with her greyhounds, especially helping her greyhound Callen have fun playing running games like lure coursing and straight racing.
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Trazodone in Veterinary Medicine BACKGROUND Trazodone is a serotonin 2A antagonist and reuptake inhibitor that has been used in human medicine as a prescription therapy for depression, aggression, sleeplessness, and anxiety since 1981.1–3 It is available in 50-, 100-, 150-, and 300-mg tablets as well as 150- and 300-mg extended-release tablets.1 No products are labeled for veterinary use. Trazodone selectively blocks serotonin reuptake, which enhances serotonin’s effects.4 It is an antagonist of 5-HT2A, H1-histaminic, and α1-adrenergic receptors at low to moderate doses, resulting in various levels of sedation.3–6 It can have hypotensive effects.4 At higher doses, trazodone acts as a serotonin agonist, and serotonin syndrome can develop.4,6 Trazodone also has anxiolytic properties, but the exact mechanism of action is unknown.4 USE IN VETERINARY MEDICINE In 2008, Gruen and Sherman studied 56 dogs prescribed trazodone in combination with other primary behavior therapies and discovered that trazodone seemed to offer therapeutic benefit with relatively minimal adverse effects.7 Since then, studies have investigated the benefit of trazodone in postorthopedic surgery treatment plans involving confinement to enhance calm behavior and reduce anxiety in hospitalized dogs. Trazodone has generally been shown to be beneficial and relatively safe. Adverse events associated with trazodone can be divided into behavioral and systemic signs. Adverse | May/June 2017
Peer Reviewed | todaysveterinarytechnician.com TOXICOLOGY TALK
shutterstock.com/Gabriel Scott
Studies have investigated the benefit of trazodone to enhance calm behavior and reduce anxiety in hospitalized dogs.
events previously reported in the literature include drugged or “spacy” behavior, drowsiness, panting, anxiety/restlessness/ agitation, vomiting/gagging, behavioral change (counter surfing and trash raiding), excitation, sedation, increased hunger, colitis, and aggression (growling).5,7,8 In veterinary medicine, trazodone is generally dosed at 1.7 to 19.5 mg/kg/d on a daily or as-needed basis with immediate action (not extended-release) tablets and can be given with food.1 When administered in combination with tricyclic antidepressants or selective serotonin reuptake inhibitors, it is recommended to begin dosing trazodone at 2 to 5 mg/kg and increase as needed to a maximum dose of 14 mg/kg/d.1 Trazodone should be administered about an hour before potential anxiety-inducing stimuli, as its onset of action is approximately 30 to 60 minutes.1,5 Gruen and colleagues reported owner-observed duration of effect lasting 4 hours or more.5 The parent compound has an elimination halflife of approximately 7 hours in immediaterelease tablets.1 Trazodone undergoes extensive metabolism in the liver and is predominately excreted via the kidneys.1,4
EXPOSURE Incidence and Clinical Signs The ASPCA Animal Poison Control Center reported 417 incidences involving singleagent trazodone exposures in 379 dogs from 2009 to 2013.1 In 104 dogs experiencing adverse effects, sedation and lethargy were reported in 43% of the dogs. Ataxia was reported in 16% and vomiting in 14%. Overall, lethargy, sedation, depression, somnolence, and subdued behavior are considered common signs of trazodone exposure.9 Additional information on signs reportedly exhibited by dogs exposed to trazodone alone from January 2003 to November 2016 and the lowest dose at which each sign was seen is provided in TABLE 1. Management Decontamination measures are an important component of exposure management. Induction of emesis within 1 hour of exposure is recommended in asymptomatic patients if no contraindications to emesis exist.9 Activated charcoal with sorbitol may be recommended in large exposures only.9 TODAY’SVETERINARYTECHNICIAN
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Trazodone in Veterinary Medicine PEER REVIEWED
Treatment of trazodone overdose generally consists of symptomatic and supportive care. Although adverse effects are often reported, relatively few cases have involved serious signs and no deaths are attributed to trazodone exposure to date.9 Special attention should be given to ensuring maintenance of cardiac output and being attentive to signs of hyperthermia or hypothermia and correcting as needed.9,11 IV fluid therapy may be needed to maintain blood pressure.6,9 Diazepam is the drug of choice for managing tremors or seizures, and atropine is suggested for treatment of bradycardia.6,9 Being aware of signs associated with serotonin syndrome is important as this can be a serious and potentially life-threatening condition to manage. Serotonin syndrome develops as a result of an overabundance of serotonin in the central nervous system.6 It can be a risk in cases of exposure to high doses of trazodone.1,4 Clinical signs of serotonin syndrome in dogs, in order of most to least common, include vomiting, diarrhea, seizures,
TABLE 1 Signs Associated With Trazodone Exposure in Dogs10 SIGN
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LOWEST DOSE (MG/KG) AT WHICH SIGN WAS SEEN
Lethargy
0.55
Depression/vomiting
1.35
Ataxia
1.7
Diarrhea
2.82
Hyperactivity
3.8
Hypotension
5.94
Hyperesthesia
6.06
Vocalization
6.6
Tremors
8.17
Disorientation
8.28
Tachycardia/hypertension
8.83
Hyperthermia
11.8
Collapse
12.99
Mydriasis/bradycardia
16.23
Seizure
78.7
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hyperthermia, hyperesthesia, depression, mydriasis, vocalization, death, blindness, hypersalivation, dyspnea, ataxia/paresis, disorientation, hyperreflexia, and coma.1 Cyproheptadine, a serotonin antagonist, helps combat serotonin syndrome signs.6,11 Phenothiazines should be used cautiously because of potential hypotensive effects.6 Interaction With Other Drugs Trazodone interacts with numerous drugs, and some of these interactions may have clinically significant effects. Of special interest are medications that may be strong inhibitors or inducers of cytochrome P450 3A4 (CYP3A4) isoenzyme, which is involved in trazodone metabolism.4 Azole antifungals (eg, ketoconazole, itraconazole, fluconazole) and macrolide antibiotics (eg, erythromycin, telithromycin, clarithromycin) are CYP3A4 inhibitors and thus may enhance the effect of trazodone.1,4 Carbamazepine, phenobarbital, phenytoin, rifampicin, and modafinil, which are CYP3A4 inducers, may decrease the effect of trazodone.1,4,9 Extreme caution should be used with concomitant trazodone and fluoxetine use and/ or exposure as it is believed that fluoxetine may inhibit metabolism of trazodone.1,4 Additionally, fluoxetine and other serotonergic medications (eg, paroxetine, sertraline, amitriptyline, clomipramine, amphetamines, dextromethorphan) as well as monoamine oxidase inhibitors (eg, phenelzine, amitraz, selegiline), metoclopramide, and tramadol, could heighten the risk of serotonin syndrome when combined with trazodone.1,4,6,8 Serotonin syndrome patients with severe cardiac disease or renal and/or hepatic function deficits should be monitored very closely and may merit additional treatment measures.1 Prognosis The prognosis for patients exposed to trazodone is generally good, especially when serotonin syndrome has not developed. Signs generally resolve in 12 to 24 hours.6 ď Ž
Peer Reviewed | todaysveterinarytechnician.com TOXICOLOGY TALK
References 1. Plumb DC. Trazodone HCl. In: Veterinary Drug Handbook. 8th ed. Ames: John Wiley and Sons; 2016. 2. Trazodone (Poisindex Managements). In: POISINDEX® System (electronic version). Greenwood Village, CO: Truven Health Analytics. Available at: micromedexsolutions.com. Accessed December 2016. 3. Gruen ME. Beyond the front line: trazodone and other ancillary treatments for anxiety. Vet Med Forum May 2012 cvm.ncsu.edu/wp-content/uploads/2015/06/Gruen_ VetMedForum_May2012.pdf. Accessed December 2016. 4. McEvoy GK, ed. Trazodone. In: AHFS Drug Information 2014. Bethesda, MD: American Society of Health-System Pharmacists; 2014:2450-2454. 5. Gruen ME, Roe SC, Griffith E, et al. Use of trazodone to facilitate postsurgical confinement in dogs. JAVMA 2014;245:296-301. 6. Wismer TA. Antidepressant drug overdoses in dogs. Vet Med 2000;95(7):520-525. 7. Gruen ME, Sherman BL. Use of trazodone as an adjunctive agent in the treatment of canine anxiety disorders: 56 cases (1995-2007). JAVMA 2008;233:19021907. 8. Gilbert-Gregory SE, Stull JW, Rice MR, et al. Effects of trazodone on behavioral signs of stress in hospitalized dogs. JAVMA 2016;249:1281-1291. 9. ASPCA Animal Poison Control Center. Trazodone vet protocol. Unpublished data. 10. ASPCA Animal Poison Control Center. AnTox database. Unpublished data. 11. Wismer TA. Antidepressant drug overdoses. Vet Tech 2006;27(5):278-281.
CAUTION: Federal (USA) law restricts this drug to use by or on the order of a licensed veterinarian. Description: NexGard® (afoxolaner) is available in four sizes of beef-flavored, soft chewables for oral administration to dogs and puppies according to their weight. Each chewable is formulated to provide a minimum afoxolaner dosage of 1.14 mg/lb (2.5 mg/ kg). Afoxolaner has the chemical composition 1-Naphthalenecarboxamide, 4-[5- [3-chloro-5-(trifluoromethyl)-phenyl]-4, 5-dihydro-5-(trifluoromethyl)-3-isoxazolyl]-N-[2-oxo-2-[(2,2,2-trifluoroethyl)amino]ethyl. Indications: NexGard kills adult fleas and is indicated for the treatment and prevention of flea infestations (Ctenocephalides felis), and the treatment and control of Black-legged tick (Ixodes scapularis), American Dog tick (Dermacentor variabilis), Lone Star tick (Amblyomma americanum), and Brown dog tick (Rhipicephalus sanguineus) infestations in dogs and puppies 8 weeks of age and older, weighing 4 pounds of body weight or greater, for one month. Dosage and Administration: NexGard is given orally once a month, at the minimum dosage of 1.14 mg/lb (2.5 mg/kg). Dosing Schedule: Body Weight 4.0 to 10.0 lbs. 10.1 to 24.0 lbs. 24.1 to 60.0 lbs. 60.1 to 121.0 lbs. Over 121.0 lbs.
Afoxolaner Per Chewables Chewable (mg) Administered 11.3 One 28.3 One 68 One 136 One Administer the appropriate combination of chewables
NexGard can be administered with or without food. Care should be taken that the dog consumes the complete dose, and treated animals should be observed for a few minutes to ensure that part of the dose is not lost or refused. If it is suspected that any of the dose has been lost or if vomiting occurs within two hours of administration, redose with another full dose. If a dose is missed, administer NexGard and resume a monthly dosing schedule. Flea Treatment and Prevention: Treatment with NexGard may begin at any time of the year. In areas where fleas are common year-round, monthly treatment with NexGard should continue the entire year without interruption. To minimize the likelihood of flea reinfestation, it is important to treat all animals within a household with an approved flea control product. Tick Treatment and Control: Treatment with NexGard may begin at any time of the year (see Effectiveness). Contraindications: There are no known contraindications for the use of NexGard. Warnings: Not for use in humans. Keep this and all drugs out of the reach of children. In case of accidental ingestion, contact a physician immediately. Precautions: The safe use of NexGard in breeding, pregnant or lactating dogs has not been evaluated. Use with caution in dogs with a history of seizures (see Adverse Reactions). Adverse Reactions: In a well-controlled US field study, which included a total of 333 households and 615 treated dogs (415 administered afoxolaner; 200 administered active control), no serious adverse reactions were observed with NexGard. Over the 90-day study period, all observations of potential adverse reactions were recorded. The most frequent reactions reported at an incidence of > 1% within any of the three months of observations are presented in the following table. The most frequently reported adverse reaction was vomiting. The occurrence of vomiting was generally self-limiting and of short duration and tended to decrease with subsequent doses in both groups. Five treated dogs experienced anorexia during the study, and two of those dogs experienced anorexia with the first dose but not subsequent doses. Table 1: Dogs With Adverse Reactions. Treatment Group Afoxolaner
Vomiting (with and without blood) Dry/Flaky Skin Diarrhea (with and without blood) Lethargy Anorexia
N1 17 13 13 7 5
Oral active control
% (n=415) 4.1 3.1 3.1 1.7 1.2
N2 25 2 7 4 9
% (n=200) 12.5 1.0 3.5 2.0 4.5
Number of dogs in the afoxolaner treatment group with the identified abnormality. 2 Number of dogs in the control group with the identified abnormality. In the US field study, one dog with a history of seizures experienced a seizure on the same day after receiving the first dose and on the same day after receiving the second dose of NexGard. This dog experienced a third seizure one week after receiving the third dose. The dog remained enrolled and completed the study. Another dog with a history of seizures had a seizure 19 days after the third dose of NexGard. The dog remained enrolled and completed the study. A third dog with a history of seizures received NexGard and experienced no seizures throughout the study. To report suspected adverse events, for technical assistance or to obtain a copy of the MSDS, contact Merial at 1-888-6374251 or www.merial.com/NexGard. For additional information about adverse drug experience reporting for animal drugs, contact FDA at 1-888-FDA-VETS or online at http://www.fda.gov/AnimalVeterinary/SafetyHealth. Mode of Action: Afoxolaner is a member of the isoxazoline family, shown to bind at a binding site to inhibit insect and acarine ligand-gated chloride channels, in particular those gated by the neurotransmitter gamma-aminobutyric acid (GABA), thereby blocking preand post-synaptic transfer of chloride ions across cell membranes. Prolonged afoxolaner-induced hyperexcitation results in uncontrolled activity of the central nervous system and death of insects and acarines. The selective toxicity of afoxolaner between insects and acarines and mammals may be inferred by the differential sensitivity of the insects and acarines’ GABA receptors versus mammalian GABA receptors. Effectiveness: In a well-controlled laboratory study, NexGard began to kill fleas four hours after initial administration and demonstrated >99% effectiveness at eight hours. In a separate well-controlled laboratory study, NexGard demonstrated 100% effectiveness against adult fleas 24 hours post-infestation for 35 days, and was ≥ 93% effective at 12 hours post-infestation through Day 21, and on Day 35. On Day 28, NexGard was 81.1% effective 12 hours post-infestation. Dogs in both the treated and control groups that were infested with fleas on Day -1 generated flea eggs at 12- and 24-hours post-treatment (0-11 eggs and 1-17 eggs in the NexGard treated dogs, and 4-90 eggs and 0-118 eggs in the control dogs, at 12- and 24-hours, respectively). At subsequent evaluations post-infestation, fleas from dogs in the treated group were essentially unable to produce any eggs (0-1 eggs) while fleas from dogs in the control group continued to produce eggs (1-141 eggs). In a 90-day US field study conducted in households with existing flea infestations of varying severity, the effectiveness of NexGard against fleas on the Day 30, 60 and 90 visits compared with baseline was 98.0%, 99.7%, and 99.9%, respectively. Collectively, the data from the three studies (two laboratory and one field) demonstrate that NexGard kills fleas before they can lay eggs, thus preventing subsequent flea infestations after the start of treatment of existing flea infestations. In well-controlled laboratory studies, NexGard demonstrated >97% effectiveness against Dermacentor variabilis, >94% effectiveness against Ixodes scapularis, and >93% effectiveness against Rhipicephalus sanguineus, 48 hours post-infestation for 30 days. At 72 hours post-infestation, NexGard demonstrated >97% effectiveness against Amblyomma americanum for 30 days. Animal Safety: In a margin of safety study, NexGard was administered orally to 8 to 9-week-old Beagle puppies at 1, 3, and 5 times the maximum exposure dose (6.3 mg/kg) for three treatments every 28 days, followed by three treatments every 14 days, for a total of six treatments. Dogs in the control group were sham-dosed. There were no clinically-relevant effects related to treatment on physical examination, body weight, food consumption, clinical pathology (hematology, clinical chemistries, or coagulation tests), gross pathology, histopathology or organ weights. Vomiting occurred throughout the study, with a similar incidence in the treated and control groups, including one dog in the 5x group that vomited four hours after treatment. In a well-controlled field study, NexGard was used concomitantly with other medications, such as vaccines, anthelmintics, antibiotics (including topicals), steroids, NSAIDS, anesthetics, and antihistamines. No adverse reactions were observed from the concomitant use of NexGard with other medications. Storage Information: Store at or below 30°C (86°F) with excursions permitted up to 40°C (104°F). How Supplied: NexGard is available in four sizes of beef-flavored soft chewables: 11.3, 28.3, 68 or 136 mg afoxolaner. Each chewable size is available in color-coded packages of 1, 3 or 6 beef-flavored chewables. 1
Toxicology Talk is written and reviewed by members of the American Society for the Prevention of Cruelty to Animals (ASPCA) Animal Poison Control Center (APCC). The mission of the APCC is to help animals exposed to potentially hazardous substances, which it does by providing 24-hour veterinary and diagnostic treatment recommendations from specially trained veterinary toxicologists. It also protects and improves animal lives by providing clinical toxicology training to veterinary toxicology residents, consulting services, and case data review. The ASPCA APCC includes a full staff of veterinarians, including board-certified toxicologists, certified veterinary technicians, and veterinary assistants, and its state-of-the-art emergency call center routinely fields requests for help from all over the world, including South America, Europe, Asia, and the Pacific Islands.
NADA 141-406, Approved by FDA Marketed by: Frontline Vet Labs™, a Division of Merial, Inc. Duluth, GA 30096-4640 USA Made in Brazil. ®NexGard is a registered trademark, and TMFRONTLINE VET LABS is a trademark, of Merial. ©2015 Merial. All rights reserved. 1050-4493-03 Rev. 1/2015
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How Often Does Treatment Follow the Guidelines? VET REPORT VITALS
VET REPORT VITALS MEET THE AU T H O R S
How Often Does Treatment Follow the Guidelines?
Rachel Beck, CVT, PMP Banfield Pet Hospital Portland, Oregon
PRACTITIONERS’ ATTITUDES TOWARD ANTIMICROBIAL RESISTANCE Antimicrobials are a cornerstone of treatment for many conditions, and their use can be critical for patient quality of life and survival. As such, antimicrobial resistance (AMR) not only affects the provision of safe and effective care, but also represents a critical and growing threat to public health. Evidence suggests that AMR is an important concern for many companion animal practitioners, with 59% of respondents to a survey of clinical veterinarians
Rachel Beck is a certified veterinary technician and credentialed project manager on the Veterinary Medical Programs team at Banfield continued on page 58
Welcome to VET Report Vitals, a column focused on the results of the groundbreaking Banfield Veterinary Emerging Topics (VET) Report™ “Are We Doing Our Part to Prevent Superbugs? Antimicrobial Usage Patterns Among Companion Animal Veterinarians.” This report, a collaboration between the NAVC and Banfield Pet Hospital, focuses on a critical topic: antimicrobial resistance (AMR). It aims to promote prudent antimicrobial use among companion animal practitioners by contributing a baseline of antimicrobial usage data to the discussion on how to achieve better concordance with published guidelines.
Nathaniel Spofford, MPH Banfield Pet Hospital Portland, Oregon Nate Spofford is a Senior Research Specialist on Banfield’s Applied Research & Knowledge (BARK) team. He received his Bachelor of Arts
This article presents data from the report as well as findings from industry research exploring practitioners’ current attitudes toward AMR. Future articles will explore the implications of AMR for veterinary technicians and discuss strategies for improving guideline concordance in daily practice.
continued on page 58
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at a veterinary teaching hospital1 and 45% of respondents to an American Veterinary Medical Association (AVMA) survey of selfidentified companion animal practitioners2 indicating they were strongly concerned about antimicrobial-resistant infections. Despite these concerns, awareness of available resources, such as guidelines for judicious use and disease-specific treatment recommendations, remains low (BOX 1). Most respondents to the AVMA survey indicated that they would like additional guidance regarding the choice of antimicrobials for various infections (77%) and the duration of antimicrobial treatment (83%), yet 88% were unaware of the existence of antimicrobial usage guidelines created by veterinary professional associations (FIGURE 1). Given this low level of awareness, poor concordance of usage patterns with guideline recommendations might be expected. CONCORDANCE OF CURRENT USAGE PATTERNS WITH GUIDELINE RECOMMENDATIONS The availability of population-based data on antimicrobial use in companion animals from the electronic medical records of Banfield Pet Hospital provides an excellent snapshot of
shutterstock.com/Soloviova Liudmyla
Antimicrobial resistance not only affects the provision of safe and effective care, but also represents a critical and growing threat to public health.
BOX 1 What Are the Guidelines? Published guidelines on the judicious use of antimicrobials in veterinary medicine include: American Association of Feline Practitioners/ American Animal Hospital Association. Basic guidelines of judicious therapeutic use of antimicrobials. Available at: avma.org/KB/Policies/ Pages/AAFP-AAHA-Basic-Guidelines-of-JudiciousTherapeutic-Use-of-Antimicrobials.aspx. American Veterinary Medical Association. Do’s and don’ts: antimicrobial therapy. Available at: avma.org/KB/Resources/Documents/ AntibioticDoDonts_DOGpdf.pdf. American Veterinary Medical Association. Judicious therapeutic use of antimicrobials. Available at: avma.org/KB/Policies/Pages/ Judicious-Therapeutic-Use-of-Antimicrobials.aspx. Hillier A, Lloyd DH, Weese JS, et al. Guidelines for the diagnosis and antimicrobial therapy of canine superficial bacterial folliculitis (Antimicrobial Guidelines Working Group of the International Society for Companion Animal Infectious Diseases). Vet Dermatol 2014;25:163-175, e142-e163. Weese JS, Giguère S, Guardabassi L, et al. ACVIM consensus statement on therapeutic antimicrobial use in animals and antimicrobial resistance. J Vet Intern Med 2015;29:487-498.
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AWARENESS AMONG VETERINARIANS CAN BE INCREASED
45%
62%
88%
are concerned about antimicrobial-resistant infections2
feel that antimicrobials in small animal practice impact AMR2
are unaware of the 3 existing sets of antimicrobial use guidelines: urinary infections,3 superficial bacterial folliculitis,4 and respiratory infections5
PRESCRIPTION PATTERNS CAN BE IMPROVED In 2015, guideline-recommended first-line antimicrobials were not prescribed for6:
32.9%
55.8%
20.4%
78.3 %
of canine nonrecurrent urinary infections
of canine recurrent urinary infections
of canine infectious respiratory disease episodes
of canine bronchitis episodes
FIGURE 1. Data about AMR awareness and antimicrobial use in veterinary medicine.
current usage patterns in general practice. This year’s edition of the VET Report™ explored antimicrobial usage patterns among companion animal practitioners to help inform voluntary adjustments that could result in a better balance between patient care and public health. Methodology The report looked at antimicrobial usage patterns from the electronic medical records of dogs evaluated for urinary tract infections (UTIs) or respiratory tract infections (RTIs) at any of 926 general-practice Banfield Pet Hospitals over the course of a calendar year (January 1, 2015–December 31, 2015). Usage patterns were evaluated for concordance with recommendations for antimicrobial treatment (drug, dosage, frequency, and duration) of UTIs and RTIs published by the Antimicrobial Guidelines Working Group of the International Society for Companion Animal Infectious Diseases (ISCAID).3,5 Because the
primary aim was to evaluate concordance with current first-line treatment guidelines, only episodes in which a single antimicrobial was dispensed were included in the analysis. Antimicrobial Use in Urinary Tract Infections There were 24,801 episodes of canine UTI treated with a single antimicrobial at Banfield Pet Hospitals in 2015 (TABLE 1). Episodes were further classified as recurrent or nonrecurrent based on whether the patient had experienced 2 or more UTIs in the preceding 12 months. Of the 24,801 episodes evaluated, 95% were determined to be nonrecurrent in nature, whereas 5% were preceded by 2 or more UTIs in the previous year. The most recently published guidelines for care of nonrecurrent UTIs recommend initial treatment with amoxicillin (11–15 mg/kg PO q8h) or trimethoprim–sulfonamide (15 mg/kg PO q12h) for a duration of 7 days.3 Amoxicillin–clavulanate
TABLE 1 Concordance With Drug Guidelines for Treatment of UTIs and RTIs
UTIs
RTIs
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Recurrent Nonrecurrent CIRD Bacterial bronchitis
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NUMBER OF EPISODES
CONCORDANCE NOT INCLUDING AMOXICILLIN– CLAVULANATE
CONCORDANCE INCLUDING AMOXICILLIN–CLAVULANATE
23,561 (95%)
2120 (9%)
15,786 (67%)
1240 (5%)
87 (7%)
546 (44%)
23,182 (95%)
5796 (25%)
18,546 (80%)
122 (5%)
29 (22%)
n/a
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(12.5–25 mg/kg PO q8h) is described as an acceptable option, but not recommended owing to lack of evidence of the need for clavulanic acid. Based on these criteria, 9% of nonrecurrent UTI episodes received a guideline-concordant antimicrobial, although that number increases to 67% if amoxicillin– clavulanate is considered an acceptable option. For recurrent UTIs, guidelines recommend that providers consider waiting for culture and susceptibility (C&S) results before instituting therapy. In cases where immediate treatment is warranted, the same recommendations as for nonrecurrent UTIs apply, with the additional recommendations that antimicrobial therapy be given for a duration of 4 weeks and that an alternative drug class to the one used for treatment of the previous UTI be dispensed. For recurrent infections, 7% of episodes received a guideline-concordant drug, increasing to 44% if amoxicillin–clavulanate is considered concordant. Information about dosage, frequency, and duration was unavailable as structured data, so a utilization snapshot was obtained by conducting a manual review of the medical notes from a random sample of 500 UTI episodes: 250 for which amoxicillin was dispensed and 250 for which amoxicillin– clavulanate was dispensed. For amoxicillin, 34% of the reviewed prescriptions were concordant with the ISCAID recommended dosage and 14% were concordant with both the recommended frequency and duration. For amoxicillin– clavulanate, 78% of reviewed prescriptions were concordant with the recommended dosage, <1% with the recommended frequency and 28% with the recommended duration.
Antimicrobial Use in Respiratory Tract Infections There were 24,402 episodes of guidelinerelated canine respiratory disease treated with a single antimicrobial at Banfield Pet Hospitals in 2015, 95% of which were classified as canine infectious respiratory disease complex (CIRD) and 5% as bacterial bronchitis (TABLE 2). Fifteen of 17 reviewers in ISCAID’s recently published guidelines for treatment of RTI recommended first-line treatment of the bacterial component of CIRD with doxycycline (5 mg/kg PO q12h or 10 mg/kg PO q24h) for a duration of 7 to 10 days.5 Amoxicillin– clavulanate (11 mg/kg PO q12h) was considered a suitable alternative by 13 of 17 reviewers. For bacterial bronchitis, doxycycline (5 mg/kg PO q12h or 10 mg/kg PO q24h) was recommended by 16 of 17 reviewers as the preferred empirical choice while waiting for results of C&S testing. Based on these criteria, 25% of CIRD episodes were treated with a guidelineconcordant antimicrobial—increasing to 80% if amoxicillin–clavulanate is considered a suitable alternative—while 22% of bronchitis episodes received a guideline-concordant drug. The medical notes from a random sample of 500 RTI episodes were reviewed to obtain information on the dosage, frequency and duration of antimicrobial use: 250 for which doxycycline was dispensed and 250 for which amoxicillin–clavulanate was dispensed. For doxycycline, 29% of reviewed prescriptions were concordant with the ISCAID recommended dosages, 100% with the recommended frequency and 46% with the recommended
TABLE 2 Concordance With Dosage, Frequency and Duration Guidelines for Treatment of UTIs and RTIs
UTIs
RTIs
NUMBER OF RECORDS REVIEWED
RECOMMENDED DOSAGE GIVEN
RECOMMENDED FREQUENCY GIVEN
RECOMMENDED DURATION GIVEN
Amoxicillin
250
85/250 (34%)
34/250 (14%)
34/250 (14%)
Amoxicillin–clavulanate
250
194/250 (78%)
1/250 (<1%)
69/250 (28%)
Doxycycline
250
72/250 (29%)
250/250 (100%)
115/250 (46%)
Amoxicillin–clavulanate
250
14/250 (6%)
250/250 (100%)
128/250 (51%)
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duration. For amoxicillin–clavulanate, 6% of reviewed prescriptions were concordant with the ISCAID recommended dosage, 100% with the recommended frequency and 51% with the recommended duration. CLINICAL BOTTOM LINE Antimicrobial usage data from 926 generalpractice hospitals throughout the United States indicate that there is room for improved concordance with existing guidelines. Evidence suggests that low concordance may be driven by a lack of awareness of available resources. As such, strategies are needed to make the transition from publication of guidelines to incorporation of guidelines into practice. Upcoming VET Report Vitals articles will explore the implications of AMR for veterinary technicians and discuss strategies for improving guideline concordance in daily practice. References 1. Jacob ME, Hoppin JA, Steers N, et al. Opinions of clinical veterinarians at a US veterinary teaching hospital regarding antimicrobial use and antimicrobial-resistant infections. JAVMA 2015;247:938-944.
Banfield has always been dedicated to using its extensive data to provide insights to the profession on topics that can improve veterinary care for pets. The first annual Banfield Veterinary Emerging Topics (VET) Report, supported by the collaborative educational efforts of the NAVC, focuses on a critical topic: antimicrobial resistance. It is titled “Are We Doing Our Part to Prevent Superbugs? Antimicrobial Usage Patterns Among Companion Animal Veterinarians.” “We are proud to team up with the NAVC on the 2017 VET Report to raise awareness about the critical topic of antimicrobial resistance in companion animal practice and how veterinarians can address it in their own practices,” said Dr. Karen Faunt, Vice President of Medical Quality Advancement at Banfield Pet Hospital. The full report is available at Banfield.com/VETReport or VetFolio.com/VETReport.
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2. AVMA Task Force for Antimicrobial Stewardship in Companion Animal Practice. Understanding companion animal practitioners’ attitudes toward antimicrobial stewardship. JAVMA 2015;247:883-884. 3. Weese JS, Blondeau JM, Boothe D, et al. Antimicrobial use guidelines for treatment of urinary tract disease in dogs and cats: antimicrobial guidelines working group of the international society for companion animal infectious diseases. Vet Med Int 2011;2011. 4. Hillier A, Lloyd DH, Weese JS, et al. Guidelines for the diagnosis and antimicrobial therapy of canine superficial bacterial folliculitis (Antimicrobial Guidelines Working Group of the International Society for Companion Animal Infectious Diseases). Vet Dermatol 2014;25:163-175, e142-163. 5. Lappin MR, Blondeau J, Boothe D, et al. Antimicrobial use Guidelines for Treatment of Respiratory Tract Disease in Dogs and Cats: Antimicrobial Guidelines Working Group of the International Society for Companion Animal Infectious Diseases. J Vet Intern Med 2017;31:279-294. 6. Banfield Pet Hospital/North American Veterinary Community. Veterinary Emerging Topics Report: Are We Doing Our Part to Prevent Superbugs? Antimicrobial Usage Patterns among Companion Animal Veterinarians. Portland, OR: Banfield Pet Hospital, 2016.
M E E T T H E AU T H O R S continued from page 54
Rachel Beck, CVT, PMP Pet Hospital. She currently leads a team of project managers who specialize in implementation. Having been in the veterinary field for over 15 years, she has served roles both in hospitals and at Banfield’s central office. She is passionate about engaging the whole veterinary team in proactive health and wellness as well as about career pathing for paraprofessionals in the industry. She resides in Portland, Oregon, with her significant other and 2 cats.
Nathaniel Spofford, MPH degree from the University of Puget Sound and his Master of Public Health degree from Portland State University. Before joining Banfield, Nate worked in clinical, behavioral, and public health research at Oregon Health & Science University. Nate is dedicated to conducting populationbased research to support the practice of evidence-based medicine. He currently lives in Portland, Oregon, with his wife Kenzin, daughter Madeleine, and cat Smallie.
todaysveterinarytechnician.com WHAT MOVES YOU
Stories of Resilience “What moves you?” If I had answered this question 5 months ago, my answer might have been very different than it is now. I would likely have included a list that had a professional tone, such as: (1) the tremendous amount of exciting change that is happening within our profession; (2) the many opportunities available as a result of this change, and (3) how the growing opportunities are increasing career advancement pathways. Although I still wholeheartedly agree with that list, a recent life-changing event now inspires a more personal tone to my response.
WHAT MOVES YOU? Veterinary technicians are the heart of veterinary medicine. We are passionate and dedicated, and we each have a story to tell. Today’s Veterinary Technician wants to hear yours! What drives you? What inspires you? What moves you?
Deborah A. Stone, MBA, PhD, CVPM StoneVPM
Send us your story at TVTech_submissions@NAVC. com. Submissions should be approximately 500 words or less and may be posted on our website or edited for publication in the journal. Tell us your story!
MY STORY I wear many different hats in the veterinary profession, including practice manager, consultant, educator, author, lecturer, and musician. Specifically, educating about the well-being of veterinary professionals is a passion of mine, and I am thrilled to see that well-being issues have become somewhat of a “movement” within our profession. Late last year, while working on multiple projects and preparing for significant work travel, I felt a suspicious lump on my neck. As I teach veterinary team members about self-care, I took time out from my busy work schedule to visit my doctor. Although taking the time was important, I honestly had not planned on spending much time dealing with this personal issue. I suspected it would be nothing more than an infection. After several weeks of diagnostics, I received the answer: tongue cancer. I was in tremendous disbelief. This was not possible. How did I get tongue cancer, especially since I’ve never smoked a cigarette in my life? Would I be able to speak and sing again or would it be through an unfamiliar voice? I had an endless number of questions as well as a growing mix of emotions. Treatment involved an aggressive 7-week course of radiation and chemotherapy. The love and support I received from friends, family, and colleagues was critical. I actually took some of the advice I share with veterinary teams and learned to ask for help; I surrendered to the fact that I didn’t have to do everything myself.
“ Our pathways in dealing with difficult life events won’t always be the same, but it may be an inspirational word or story of another person that resonates and helps us get through.” —Deborah A. Stone
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Deb undergoing radiation therapy in her “supermask.”
In addition to their generous support, some folks shared stories of resilience about difficult times in their lives and how they pushed through. The stories weren’t all about cancer or medical issues; however, they all included some challenging life event that presented seemingly insurmountable obstacles. As people shared these experiences with me, they also seemed to demonstrate authentic gratitude for the journey needed to overcome them. One story I held onto was of a friend who had dealt with a serious health condition several years ago. He actually shared his story before I even had a diagnosis, so I listened
“Moving” Stories When I lecture on the importance of well-being and discuss the evolution of well-being issues in our profession, I use the term “movement” to reflect the increased attention these issues are receiving. Notably, this attention started with compelling, individual news stories about highprofile suicides, then expanded to an increase in studies and education. The result is what I see as almost a profession-wide movement to increase our understanding of well-being issues as well as how to better care for ourselves. Although the stories that inspired it, especially those of suicide, are tragic, their legacy is, I hope, helping others pull through.
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and was amazed at his strength and positivity in dealing with intense medical treatment. Although the story and final outcomes were amazing, what continued to resonate with me throughout my treatment was one word he used: psychological. He said throughout the pain, fear, and unknown outcomes during his treatment, his biggest challenges were the psychological ones. It wasn’t intentional, but that word stayed with me throughout my treatment, especially as I experienced my own fear of the unknown. It pushed me through the entire course, especially if I started feeling really sorry for myself or thinking I would never feel “normal” again. I successfully made it through all of my treatment and am now on the path to making a full recovery, thanks to the support of many people…and stories. WE ALL HAVE A STORY At some point, everyone will experience a life event they feel presents overwhelming odds. Our challenges may vary significantly and may not always be life-threatening or medically related, yet they are all life-changing. Our pathways in dealing with difficult life events won’t always be the same, but it may be an inspirational word or story of another person that resonates and helps us get through. FINDING STORIES OF RESILIENCE Veterinary technicians create stories of resilience every day. The care, attention, and commitment they provide to their patients is often life-saving and life-changing. Stories of resilience can be found right under our nose and often in our very own workplace. Perhaps a client shares a story in the exam room, or a colleague reaches out because they see signs that you may be struggling. Remaining open, mindful, and present provides opportunities to hear stories that can inspire you for a lifetime. You never know when someone’s story will help pull you through difficult times. You also never know when your very own story may help someone find the hope, strength, and pathway to navigate their own challenging journey.
Leaders, Step Forward Are you a veterinary technician or veterinary nurse with a talent for leadership? Would you like to attend the 2018 VMX (formerly the NAVC Conference) on a leadership scholarship? Here’s your chance! Last year, the NAVC said a final farewell to Dr. Earl H. Rippie, Jr, former past president and secretary-treasurer, when he passed away in June. Dr. Rippie, a leader in the veterinary profession in his own right, was also a champion of veterinary technicians. He recognized that technicians are the spokes in the wheel of the practice and the heart of the hospital. He believed that veterinary technicians should be the first ones to see the client in the exam room, that they are equal voices on the veterinary team, and that they bring unparalleled value to the health and well-being of animals. The new Dr. Earl H. Rippie Veterinary Technician Leadership Scholarship honors Dr. Rippie’s memory and his appreciation for veterinary technicians. It recognizes veterinary technicians and veterinary nurses who have demonstrated leadership abilities and have made a positive impact on the growth of the profession or in their practice. It includes: ÆÆ Free registration, six (6) nights accommodations, and six (6) days per diem for the 2018 VMX ÆÆ Economy class airfare to Orlando for the 2018 VMX ÆÆ One Masterclass at the 2018 VMX ÆÆ Invitation to 2018 VMX special events as a VIP ÆÆ Preconference meet/greet with the NAVC Board of Directors and other scholars To be eligible for the scholarship, domestic applicants must be credentialed according to their state requirements; international applicants must be a qualified veterinary technician/nurse in their country of residence. Three scholarships (two domestic and one international) will be awarded for the 2018 VMX.
The submission deadline is July 1, 2017.
What You Need to Apply 1. A completed online application form 2. Your curriculum vitae or resume 3. Two letters of endorsement by a colleague, mentor, or supervisor who can attest to your leadership abilities and impact on the growth of the profession and/or their practice 4. Proof of membership (letter of good standing that includes years as a member) in a local, state, regional, provincial, or national veterinary technician association or specialty academy 5. A 3- to 5-minute video about yourself, your passion for their profession, and how you have demonstrated your leadership abilities For forms and more details, visit NAVC.com/scholarships.
CAREERS
PEER REVIEWED
Use Your Skills as a Force for Good! Use your veterinary nursing skills as a force for good! Located in Buffalo Grove, IL, Veterinary Specialty Center has been named a top workplace by the Chicago Tribune. We encourage technicians to take an active role in case management, attend CE, and support them as they work toward their VTS certification. Contact Sheila Haske at shaske@vetspecialty.com or call 847.459.7535., ext. 1515. Learn more at vetspecialty.com/contact-us/jobs
Advertiser Index Atlantic Coast Veterinary Conference ACVC 2017 acvc.org . . . . . . . . . . . . . . . . . . . . . . . . 45 Bayer Seresto animalhealth.bayer.com . . . . 23
VetFolio vetfolio.com . . . . . . . . . . . . . . . . . . . 43 VMX 2018 navc.com . . . . . . . . . . . . . . . . . . . . . . 15 Nestlé Purina NeuroCare diet purinaproplanvets.com . . . . . . . 5
Boehringer Ingelheim Vetmedin boehringer-ingelheim.com . . . . . . . . . . . . inside front cover, 2
Penn Foster Diploma programs pennfoster.edu . . . . . . . . . . . . . . . 33
Merial Heartgard heartgard.com . . . . . . . . . . . . . . . . . . 7
PRN Pharmacal University of PRN universityprn.com . . . . . . . . . . . . 11
NexGard nexgardfordogs.com . . . . 49, 53
Veterinary Specialty Center Recruitment vetspecialty.com . . . . . . . . . . . . . 61
Recombitek 4 Lepto vaccines vaccinateyourpet.net . . . . . . . . . . . . . . . . . . . . . . . back cover
Virbac Sentinel virbacpets.com . . . . . . . . . . 34, 35
NAVC LIVE: Portland navc.com . . inside back cover
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FINAL THOUGHTS
Bully Tactics
MEET THE AU TH O R
Recently, a technician contacted me for some private coaching because she was feeling bullied by one of the veterinarians in her practice. She told me how he loses his temper at the slightest things, throws things (but not at her), and is verbally abusive toward her. All of this makes her feel incredibly incompetent, even though deep down she knows she’s a good tech. The Merriam-Webster Dictionary defines a bully as a blustering, browbeating person; especially one who is habitually cruel, insulting, or threatening to others who are weaker, smaller, or in some way vulnerable. (This definition made me realize I didn’t know what browbeating meant, so in the event that you don’t know either, here is the Merriam-Webster take on that: to intimidate or disconcert by a stern manner or arrogant speech. If you are fortunate enough to not know anyone like this personally, you’ve seen them on TV or in the movies [BOX 1].) As a veterinary technician, you may work in private practice, an animal shelter, research, or elsewhere. It may not be a veterinarian who is the bully; it could be another tech, a supervisor, a manager, a board member, a client, or a member of the general public. Regardless of who is doing the bullying, it’s important to call it out and name it bullying if that’s what it is.
Julie Squires, CCFS Rekindle, LLC Julie is a compassion fatigue specialist who brings a unique perspective and approach to support the sustained energy and passion of animal workers. Her company, Rekindle LLC, offers on-site compassion fatigue training to veterinary hospitals, animal shelters, lab animal research facilities, and other animal organizations. Julie has 25 years of experience within the veterinary field and with leading organizations. She has developed and executed training, workshops, and 1:1 coaching for major companies in the animal health industry. She obtained her certification as a compassion fatigue specialist through the Traumatology Institute. Julie’s clients also gain from her experience as a certified life coach and corporate wellness specialist.
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THE TRUTH ABOUT BULLYING Here is the truth about bullying: it tells you everything about the person doing the bullying and nothing about yourself. Bullies have issues with self-esteem. Some of them have very low self-esteem, but others regard themselves quite favorably. Bullies enjoy manipulating others and focus on people whom they think will let them get away with it. So what does that mean? It means don’t be a victim, because it leaves you powerless. If you believe others can hurt you and your feelings are based on their actions, you will be powerless. However, if you acknowledge that YOU are responsible for how you feel, you will be much more prepared to deal with a bully. Others can behave however they want, but you get to decide how you’re going to feel about it by deciding how you’re going to think about it. |
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todaysveterinarytechnician.com FINAL THOUGHTS
shutterstock.com/gpointstudio
“Never be bullied into silence. Never allow yourself to be made a victim. Accept no one’s definition of your life, but define yourself.” —Tim Fields
BULLYING IN THE WORKPLACE “No one can make you feel inferior without your consent.” — Eleanor Roosevelt The Workplace Bullying Institute defines workplace bullying as follows1: Workplace Bullying is repeated, healthharming mistreatment of one or more
BOX 1 What Does a Bully Look Like? Bullying is not new. Bullies are found throughout recorded history. While historical bullies are predominantly male, female bullies exist (known as “mean girls”). Some of the most famous TV and film bullies include the following: Biff Tannen, Back to the Future Johnny Lawrence, The Karate Kid Nelson Muntz, The Simpsons Scut Farkus, A Christmas Story Draco Malfoy, Harry Potter Nelly Olson, Little House on the Prairie Angelica Pickles, Rugrats Gordon Ramsey, Hell’s Kitchen Eric Cartman, South Park
persons (the targets) by one or more perpetrators. It is abusive conduct that is: ÆÆ Threatening, humiliating, or intimidating, or ÆÆ Work interference—sabotage—which prevents work from getting done, or ÆÆ Verbal abuse In the workplace, the rules are different from those in our personal lives. Most veterinary practices and organizations have rules that employees must follow or risk termination. Find out what the policy is on bullying if you are being bullied. Report it to your human resources representative or manager, so there is a record. Unfortunately, not much happens in most cases, even with a bullying incident being documented. Sometimes the bully is talented, productive, and highly regarded by senior management. Because of that, many organizations do nothing. You should be aware that workplace bullying has potential legal liability, and some of the biggest companies (Microsoft, Dish Network, etc.) have found themselves paying big bucks to employees who were wronged in the workplace. See BOX 2 for a list of online resources about workplace and other types of bullying. TODAY’SVETERINARYTECHNICIAN
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TAKING THE BULL BY THE HORNS I’m all about personal empowerment. I’ve learned that I can’t control much in this world. However, I can control where I work, and changing jobs is certainly a viable option if you are being bullied at work and management has not been willing or able to stop it. That all being said, you still have the power to choose what to think about bullying. Your thoughts are your superpower because you can decide to think ANYTHING you want about it. Anything. Isn’t that great? If the bullying is troubling you, it’s because of the meaning you are giving it, perhaps subconsciously. She doesn’t respect me. I’m not good enough. There’s something wrong with me. He doesn’t like me. He shouldn’t be allowed to behave like that. Why can she get away with that? Who does he think he is talking to like that? Bullies can—and will—say what they want, but you get to decide if you think it’s true, or if you think it’s just them trying to feel better about themselves. You may even decide to think the bully has no other skills with which to connect, so instead he or she chooses to connect with you from a negative place.
Once a Bully, Maybe Not Always a Bully In my own life, my brother bullied me tirelessly about my weight when I was growing up. I didn’t have the knowledge that I have now, nor the tools. So instead, I kept emotionally eating and gained more weight. Then he bullied me more. This kind of sibling bullying is not uncommon. However, in what might seem to be an ironic twist, my brother is now a school psychologist, and part of his job involves working with kids who are bullied at school! It goes to show that sometimes the bully takes stock, realizes his effect on others, and chooses for it to be productive rather than destructive. Today I have a great relationship with my brother and am really proud of who he is.
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May/June 2017
When you can get a little perspective on the situation, you might be able to see right through the bully. These are people who are deeply disconnected from themselves and from their own feelings as well as the feelings of others. In almost all situations, they are people trying to make themselves feel better or more powerful at the expense of others. But remember… ÆÆ You don’t need others to respect you, if you respect yourself. ÆÆ You don’t need others to regard you as competent, if you know you are. ÆÆ You don’t need anyone to like you, if you already like yourself. ÆÆ You don’t need to care about how others act, if you act appropriately yourself. Our thoughts, not our circumstances, cause our feelings. Bullying is a circumstance that has no negative meaning until you think something negative about it. Someone saying ANYTHING to you is not what causes your feelings; what you think about what they said is what does. So, perhaps you can think a bully is just being a jerk and go on making your difference in this world. Why not? “If there are no heroes to save you, then you be the hero.” — Denpa Kyoshi. Reference 1. Workplace Bullying Institute. The WBI definition of workplace bullying. workplacebullying.org/individuals/problem/definition/. Accessed March 2017.
BOX 2 Bullying Resources To take action if you are bullied in the workplace, check out the AARP’s “What to Do If You Are Bullied at Work.” (aarp.org/ work/job-hunting/info-11-2013/handlebullying-on-the-job.html) Other great resources include the following: workplacebullying.org stopbullying.gov/resources safekids.com/bullying-cyberbullyingresources/
LIVE, UNIQUE & INTERACTIVE LEARNING
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AU G U ST 20-23, 2017 T H E H I LTO N P O R T L A N D & EXECUT IVE TOW ER The NAVC is extending its popular educational platform to the great Northwest with an innovative experience unlike any conference you’ve seen before.
NAVC LIVE will feature professional “case theater” veterinarian/client presentations, live-streamed general sessions, short communications, Q&A for remote attendees and clinical content in a non-clinical setting, as well as engaging networking opportunities.
F E AT U R E D E D U C AT I O N A L T R AC K S • Ain’t Doin’ Right: Approaches to the Clinically Vague • Behavior • Cardiology • Dermatology Sponsored by:
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Endocrinology Oncology Ophthalmology Pursuit of Happiness: Practice Challenges, Conflict Management and Wellbeing in Veterinary Medicine
Registration now open at NAVC.com/Live
Dogs take enough risks on their own. Count on RECOMBITEK® 4 Lepto Combos for comprehensive leptospirosis protection in its purest form.1
Protect your patients from the rising threat of leptospirosis with the nonadjuvanted vaccine that offers four-way protection against disease and shedding.* Available in DAP and DAPP combinations! The only vaccine that prevents leptospirosis caused by Leptospira canicola, L. grippotyphosa, L. icterohaemorrhagiae, and aids in the prevention of L. pomona.
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Prevents your patients from shedding bacteria into the environment after exposure*
Nobivac: A portfolio of advanced vaccines for the well-being of canine family members [brochure]. Summit, NJ: Merck Animal Health; 2013. MAH-VC-851.
* Indicated for the prevention of leptospirosis and leptospiruria caused by L. canicola, L. grippotyphosa and L. icterohaemorrhagiae and as an aid in the prevention of leptospirosis and leptospiruria caused by L. pomona. ** L. grippotyphosa Merial is now part of Boehringer Ingelheim. ®RECOMBITEK is a registered trademark of Merial. ©2017 Merial, Inc., Duluth, GA. All rights reserved. VAC16TRADEADS2 (03/17).
The only bacterin to provide a 15-month duration of immunity**