Top 5 Cytologic Findings in Aspirates of Enlarged

May 2019

A Peer-Reviewed Journal | cliniciansbrief.com

TOP 5 CYTOLOGIC FINDINGS IN ASPIRATES OF ENLARGED

IN THIS ISSUE LYMPH NODES

Top 5 Radiographic Variants Respiratory Distress & Inappetence Case Management Algorithm: Snake Envenomation Managing Aggressive & Fearful Dogs Neutropenia: A Differential Diagnosis List

Volume 17 Number 5

THE OFFICIAL CLINICAL PRACTICE JOURNAL OF THE WSAVA Advantage Multi® for Dogs and for Cats (imidacloprid + moxidectin) BRIEF SUMMARY: Before using Advantage Multi ® for Dogs (imidacloprid+moxidectin) or Advantage Multi ® for Cats (imidacloprid +moxidectin), please consult the product insert, a summary of which follows: CAUTION: Federal (U.S.A.) Law restricts this drug to use by or on the order of a licensed veterinarian. Advantage Multi for Dogs: WARNING • DO NOT ADMINISTER ThIS pRODUCT ORAllY. • For the first 30 minutes after application ensure that dogs cannot lick the product from application sites on themselves or other treated animals. • Children should not come in contact with the application sites for two (2) hours after application. (See Contraindications, Warnings, human Warnings, and Adverse Reactions for more information.) INDICATIONS: Advantage Multi for Dogs is indicated for the prevention of heartworm disease caused by Dirofilaria immitis and the treatment of Dirofilaria immitis circulating microfilariae in heartworm-positive dogs. Treats and controls Advantage Multi for Dogs kills adult fleas and is indicated for the treatment of flea infestations (Ctenocephalides felis). Advantage Multi for Dogs is indicated for the treatment and control of sarcoptic mange caused by Sarcoptes scabiei var.canis. Advantage Multi for Dogs is also indicated sarcoptic mange in dogs for the treatment and control of the following intestinal parasites species: Hookworms (Ancylostoma caninum) (Uncinaria stenocephala), Roundworms (Toxocara canis) (Toxascaris leonina) and Whipworms (Trichuris vulpis). Advantage Multi for Cats is indicated for the prevention of heartworm disease caused by Dirofilaria immitis. Advantage Multi for Cats kills adult fleas (Ctenocephalides felis) and is indicated for the treatment of flea infestations. Advantage Multi for Cats is also indicated for the treatment and control of ear mite (Otodectes cynotis) infestations and the intestinal parasites species Hookworm (Ancylostoma tubaeforme) and Roundworm (Toxocara cati). Ferrets: Advantage Multi for Cats is indicated for the prevention of heartworm disease in ferrets caused by Dirofilaria immitis. Advantage Multi for Cats kills adult fleas (Ctenocephalides felis) and is indicated for the treatment of flea infestations in ferrets. Every dog and cat deserves comprehensive, CONTRAINDICATIONS: Do not administer this product orally. (See WARNINGS). Do not use the Dog product (containing 2.5% moxidectin) on Cats. WARNINGS: broad-spectrum parasite protection. Advantage Multi for Dogs: For the first 30 minutes after application: Ensure that dogs cannot lick the product from application sites on themselves or other treated dogs, and separate treated dogs from one another and from other pets to reduce the risk of accidental ingestion. Ingestion of this product by dogs may cause serious adverse reactions including depression, salivation, That’s why Advantage Multi® delivers layers dilated pupils, incoordination, panting, and generalized muscle tremors. In avermectin sensitive dogsa, the signs may be more severe and may include coma and deathb. of protection against heartworms, fleas Treats ear a Some dogs are more sensitive to avermectins due to a mutation in the MDR1 gene. Dogs with this mutation may develop signs of severe avermectin toxicity if they ingest this product. The most common breeds associated with this mutation include Collies and Collie crosses. and intestinal parasites. mites in cats b Although there is no specific antagonist for avermectin toxicity, even severely affected dogs have completely recovered from avermectin toxicity with intensive veterinary supportive care. Advantage Multi for Cats: Do not use on sick, debilitated, or underweight cats. Do not use on cats less than 9 weeks of age or less than 2 lbs. body weight. Do not use on sick or debilitated ferrets. hUMAN WARNINGS: Not for human use. Keep out of the reach of children. Dogs: Children should disease ’t have to b s and cont not come in contact with the application sites for two (2) hours after application. Cats: Children rm pre on it at ro should not come in contact with the application site for 30 minutes after application. o v d e re ls tw e s to T Causes eye irritation. Harmful if swallowed. Do not get in eyes or on clothing. Avoid contact with skin. r n a Wash hands thoroughly with soap and warm water after handling. If contact with eyes occurs, a t e d e io l i hold eyelids open and flush with copious amounts of water for 15 minutes. If eye irritation develops F e or persists, contact a physician. If swallowed, call poison control center or physician immediately for H n treatment advice. Have person sip a glass of water if able to swallow. Do not induce vomiting unless told to do so by the poison control center or physician. People with known hypersensitivity to benzyl alcohol, imidacloprid, or moxidectin should administer the product with caution. In case of allergic reaction, contact a physician. If contact with skin or clothing occurs, take off contaminated clothing. Wash skin immediately with plenty of soap and water. Call a poison control center or physician for treatment advice. The Safety Data Sheet (SDS) provides additional occupational safety information. For a copy of the Safety Data Sheet (SDS) or to report adverse reactions call Bayer Veterinary Services at 1-800-422-9874. For consumer questions call 1-800-255-6826. pRECAUTIONS: Do not dispense dose applicator tubes without complete safety and administration information. Use with caution in sick, debilitated or underweight animals. The safety of Advantage Multi for Dogs has not been established in breeding, pregnant, or lactating dogs. The safe use of th Advantage Multi for Dogs has not been established in puppies and dogs less than 7 weeks of age a g or less than 3 lbs. body weight. Advantage Multi for Dogs has not been evaluated in heartworm- t n K t o i c i * positive dogs with Class 4 heartworm disease. wo h l lls ta nt s Cats may experience hypersalivation, tremors, vomiting and decreased appetite if Advantage Multi rk nt th on es rm for Cats is inadvertently administered orally or through grooming/licking of the application site. s all mo rough c tinal wo The safety of Advantage Multi for Cats has not been established in breeding, pregnant, or lactating cats. The effectiveness of Advantage Multi for Cats against heartworm infections (D. immitis) after bathing has not been evaluated in cats. Use of this product in geriatric cats with subclinical conditions has not been adequately studied. Ferrets: The safety of Advantage Multi for Cats has not been established in breeding, pregnant, and lactating ferrets. Treatment of ferrets weighing less than 2.0 lbs. (0.9kg) should be based on a risk-benefit assessment. The effectiveness of Advantage Multi for Cats in ferrets weighing over 4.4 lbs. (2.0 kg) has not been established. ADVERSE REACTIONS: heartworm Negative Dogs: The most common adverse reactions observed during field studies were pruritus, residue, medicinal odor, lethargy, inappetence and hyperactivity. heartworm positive Dogs: The most common adverse reactions observed during field studies Provide the multi-layered protection of were cough, lethargy, vomiting, diarrhea (including hemorrhagic), and inappetence. Cats: The most common adverse reactions observed during field studies were lethargy, behavioral changes, discomfort, hypersalivation, polydipsia and coughing and gagging. Ferrets: The most common Advantage Multi® to the pets in your care. adverse reactions observed during field studies were pruritus/scratching, scabbing, redness, wounds and inflammation at the treatment site; lethargy; and chemical odor. For a copy of the Safety Data Sheet (SDS) or to report adverse reactions call Bayer Veterinary Visit LayersofMulti.com or contact your Bayer Sales Representative. Services at 1-800-422-9874. For consumer questions call 1-800-255-6826. Advantage Multi is protected by one or more of the following U.S. patents: 6,232,328 and 6,001,858. NADA 141-251,141-254 Approved by FDA V-03/2016 © 2015 Bayer Bayer, the Bayer Cross, Advantage Multi are registered trademarks of Bayer. Made in Germany. *Treats and controls roundworms, hookworms and whipworms in dogs and roundworms and hookworms in cats. CAUTION: Advantage Multi® is only available from a licensed veterinarian. Dogs: WARNING: DO NOT ADMINISTER THIS PRODUCT ORALLY. For the first 30 minutes after application, ensure that dogs cannot lick the product from application sites on themselves or other treated animals. Children should not come in contact with the application sites for two (2) hours after application. (See Contraindications, Warnings, Human Warnings and Adverse Reactions for more information.) Cats: Do not use on sick, debilitated or underweight cats. Avoid oral ingestion. © 2019 Bayer, Shawnee Mission, KS 66201. Bayer, the Bayer Cross and Advantage Multi are registered trademarks of Bayer. AM19856

47830-14_Bayer_CliniciansBriefBarnDoorPrintAd_FA.indd 1 4/16/19 10:54 AM Advantage Multi® for Dogs and for Cats (imidacloprid + moxidectin) BRIEF SUMMARY: Before using Advantage Multi ® for Dogs (imidacloprid+moxidectin) or Advantage Multi ® for Cats (imidacloprid +moxidectin), please consult the product insert, a summary of which follows: CAUTION: Federal (U.S.A.) Law restricts this drug to use by or on the order of a licensed veterinarian. Advantage Multi for Dogs: WARNING • DO NOT ADMINISTER ThIS pRODUCT ORAllY. • For the first 30 minutes after application ensure that dogs cannot lick the product from application sites on themselves or other treated animals. • Children should not come in contact with the application sites for two (2) hours after application. (See Contraindications, Warnings, human Warnings, and Adverse Reactions for more information.) INDICATIONS: Advantage Multi for Dogs is indicated for the prevention of heartworm disease caused by Dirofilaria immitis and the treatment of Dirofilaria immitis circulating microfilariae in heartworm-positive dogs. Treats and controls Advantage Multi for Dogs kills adult fleas and is indicated for the treatment of flea infestations (Ctenocephalides felis). Advantage Multi for Dogs is indicated for the treatment and control of sarcoptic mange caused by Sarcoptes scabiei var.canis. Advantage Multi for Dogs is also indicated sarcoptic mange in dogs for the treatment and control of the following intestinal parasites species: Hookworms (Ancylostoma caninum) (Uncinaria stenocephala), Roundworms (Toxocara canis) (Toxascaris leonina) and Whipworms (Trichuris vulpis). Advantage Multi for Cats is indicated for the prevention of heartworm disease caused by Dirofilaria immitis. Advantage Multi for Cats kills adult fleas (Ctenocephalides felis) and is indicated for the treatment of flea infestations. Advantage Multi for Cats is also indicated for the treatment and control of ear mite (Otodectes cynotis) infestations and the intestinal parasites species Hookworm (Ancylostoma tubaeforme) and Roundworm (Toxocara cati). Ferrets: Advantage Multi for Cats is indicated for the prevention of heartworm disease in ferrets caused by Dirofilaria immitis. Advantage Multi for Cats kills adult fleas (Ctenocephalides felis) and is indicated for the treatment of flea infestations in ferrets. Every dog and cat deserves comprehensive, CONTRAINDICATIONS: Do not administer this product orally. (See WARNINGS). Do not use the Dog product (containing 2.5% moxidectin) on Cats. WARNINGS: broad-spectrum parasite protection. Advantage Multi for Dogs: For the first 30 minutes after application: Ensure that dogs cannot lick the product from application sites on themselves or other treated dogs, and separate treated dogs from one another and from other pets to reduce the risk of accidental ingestion. Ingestion of this product by dogs may cause serious adverse reactions including depression, salivation, That’s why Advantage Multi® delivers layers dilated pupils, incoordination, panting, and generalized muscle tremors. In avermectin sensitive dogsa, the signs may be more severe and may include coma and deathb. of protection against heartworms, fleas Treats ear a Some dogs are more sensitive to avermectins due to a mutation in the MDR1 gene. Dogs with this mutation may develop signs of severe avermectin toxicity if they ingest this product. The most common breeds associated with this mutation include Collies and Collie crosses. and intestinal parasites. mites in cats b Although there is no specific antagonist for avermectin toxicity, even severely affected dogs have completely recovered from avermectin toxicity with intensive veterinary supportive care. Advantage Multi for Cats: Do not use on sick, debilitated, or underweight cats. Do not use on cats less than 9 weeks of age or less than 2 lbs. body weight. Do not use on sick or debilitated ferrets. hUMAN WARNINGS: Not for human use. Keep out of the reach of children. Dogs: Children should disease ’t have to b s and cont not come in contact with the application sites for two (2) hours after application. Cats: Children rm pre on it at ro should not come in contact with the application site for 30 minutes after application. o v d e re ls tw e s to T Causes eye irritation. Harmful if swallowed. Do not get in eyes or on clothing. Avoid contact with skin. r n a Wash hands thoroughly with soap and warm water after handling. If contact with eyes occurs, a t e d e io l i hold eyelids open and flush with copious amounts of water for 15 minutes. If eye irritation develops F e or persists, contact a physician. If swallowed, call poison control center or physician immediately for H n treatment advice. Have person sip a glass of water if able to swallow. Do not induce vomiting unless told to do so by the poison control center or physician. People with known hypersensitivity to benzyl alcohol, imidacloprid, or moxidectin should administer the product with caution. In case of allergic reaction, contact a physician. If contact with skin or clothing occurs, take off contaminated clothing. Wash skin immediately with plenty of soap and water. Call a poison control center or physician for treatment advice. The Safety Data Sheet (SDS) provides additional occupational safety information. For a copy of the Safety Data Sheet (SDS) or to report adverse reactions call Bayer Veterinary Services at 1-800-422-9874. For consumer questions call 1-800-255-6826. pRECAUTIONS: Do not dispense dose applicator tubes without complete safety and administration information. Use with caution in sick, debilitated or underweight animals. The safety of Advantage Multi for Dogs has not been established in breeding, pregnant, or lactating dogs. The safe use of th Advantage Multi for Dogs has not been established in puppies and dogs less than 7 weeks of age a g or less than 3 lbs. body weight. Advantage Multi for Dogs has not been evaluated in heartworm- t n K t o i c i * positive dogs with Class 4 heartworm disease. wo h l lls ta nt s Cats may experience hypersalivation, tremors, vomiting and decreased appetite if Advantage Multi rk nt th on es rm for Cats is inadvertently administered orally or through grooming/licking of the application site. s all mo rough c tinal wo The safety of Advantage Multi for Cats has not been established in breeding, pregnant, or lactating cats. The effectiveness of Advantage Multi for Cats against heartworm infections (D. immitis) after bathing has not been evaluated in cats. Use of this product in geriatric cats with subclinical conditions has not been adequately studied. Ferrets: The safety of Advantage Multi for Cats has not been established in breeding, pregnant, and lactating ferrets. Treatment of ferrets weighing less than 2.0 lbs. (0.9kg) should be based on a risk-benefit assessment. The effectiveness of Advantage Multi for Cats in ferrets weighing over 4.4 lbs. (2.0 kg) has not been established. ADVERSE REACTIONS: heartworm Negative Dogs: The most common adverse reactions observed during field studies were pruritus, residue, medicinal odor, lethargy, inappetence and hyperactivity. heartworm positive Dogs: The most common adverse reactions observed during field studies Provide the multi-layered protection of were cough, lethargy, vomiting, diarrhea (including hemorrhagic), and inappetence. Cats: The most common adverse reactions observed during field studies were lethargy, behavioral changes, discomfort, hypersalivation, polydipsia and coughing and gagging. Ferrets: The most common Advantage Multi® to the pets in your care. adverse reactions observed during field studies were pruritus/scratching, scabbing, redness, wounds and inflammation at the treatment site; lethargy; and chemical odor. For a copy of the Safety Data Sheet (SDS) or to report adverse reactions call Bayer Veterinary Visit LayersofMulti.com or contact your Bayer Sales Representative. Services at 1-800-422-9874. For consumer questions call 1-800-255-6826. Advantage Multi is protected by one or more of the following U.S. patents: 6,232,328 and 6,001,858. NADA 141-251,141-254 Approved by FDA V-03/2016 © 2015 Bayer Bayer, the Bayer Cross, Advantage Multi are registered trademarks of Bayer. Made in Germany. *Treats and controls roundworms, hookworms and whipworms in dogs and roundworms and hookworms in cats. CAUTION: Advantage Multi® is only available from a licensed veterinarian. Dogs: WARNING: DO NOT ADMINISTER THIS PRODUCT ORALLY. For the first 30 minutes after application, ensure that dogs cannot lick the product from application sites on themselves or other treated animals. Children should not come in contact with the application sites for two (2) hours after application. (See Contraindications, Warnings, Human Warnings and Adverse Reactions for more information.) Cats: Do not use on sick, debilitated or underweight cats. Avoid oral ingestion. © 2019 Bayer, Shawnee Mission, KS 66201. Bayer, the Bayer Cross and Advantage Multi are registered trademarks of Bayer. AM19856

47830-14_Bayer_CliniciansBriefBarnDoorPrintAd_FA.indd 1 4/16/19 10:54 AM Thirty days in, heartworms are still out.

Coraxis™ (moxidectin) Topical Solution for Dogs is transdermal moxidectin that 1 dose. achieves and sustains high serum levels and keeps killing susceptible stages of heartworms for 30 days. Administered monthly, Coraxis™ also treats and 6 parasites. controls hookworms, roundworms and whipworms to work hard for your clinic and your patients. 30 days. Add the power of 30-day heartworm protection to your portfolio. Visit coraxis.com or contact your Bayer sales representative today. That’s Coraxis™.

™ (moxidectin)

CoraxisTM is not approved for the treatment of adult D. immitis. CAUTION: Federal (U.S.A.) law restricts this drug to use by or on the order of a licensed veterinarian. WARNING: DO NOT ADMINISTER THIS PRODUCT ORALLY. For the first 30 minutes after application ensure that dogs cannot lick the product from application sites on themselves or other treated animals. Children should not come in contact with the application sites for two (2) hours after application. (See Contraindications, Warnings, Human Warnings, and Adverse Reactions, for more information.) CONTRAINDICATIONS: Do not use this product on cats.

See page 2 for product information summary.

47836_Coraxis_30Days-V2_CLINICIANS BRIEF_8-125x10-875_FA.indd 1 2/14/19 2:55 PM PUBLISHER OF CLINICIAN’S BRIEF

TEAM

EDITOR IN CHIEF CHIEF VETERINARY DIRECTOR OF MANAGING EDITOR J. SCOTT WEESE OFFICER & EDITOR INTEGRATIVE CONTENT SAMANTHA FARLEY DVM, DVSc, DACVIM INDU MANI JENNIFER L. SCHORI MPS [email protected] DVM, ScD VMD, MS [email protected] Professor [email protected] [email protected] Ontario Veterinary College Ontario, Canada

CEO/FOUNDER CHIEF OF CONTENT STRATEGY EDITORIAL ASSISTANT DESIGN & PRODUCTION AMY MOHL CAROL WATKINS JEANNE MISTRETTA ELIZABETH GREEN DVM [email protected] Mistretta Design Group, LLC [email protected] [email protected] [email protected] EDITOR AT LARGE SENIOR DIRECTOR OF CONTENT ANTOINETTE PASSARETTI SENIOR GRAPHIC DESIGNER ADVERTISING MICHELLE N. MUNKRES [email protected] AMANDA BILBERY JOHN O’BRIEN MA [email protected] [email protected] [email protected] MANAGER, DIGITAL CONTENT EMILY FAISON MEDICAL EDITORS JOANNA LUNDBERG ASSOCIATE EDITORS MA PEGGY BURRIS [email protected] DRUE A. GINDLER [email protected] DVM [email protected] [email protected] JEANINE NICOSIA DIGITAL CONTENT COORDINATOR [email protected] JANE GARDINER SARAH TYLER ALEXIS USSERY DVM [email protected] [email protected] NAOMI MURRAY, DVM [email protected] [email protected] PROJECTS EDITOR CREATIVE DIRECTOR ALYSSA WATSON LINDSAY ROBERTS AARON MAYS DVM HOLLY WILLIAMS [email protected] [email protected] [email protected] [email protected]

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May 2019 cliniciansbrief.com 1 Topical Solution for Dogs BRIEF SUMMARY: Before using CoraxisTM, please consult the product insert, a summary of which follows: WARNING • DO NOT ADMINISTER THIS PRODUCT ORALLY • For the first 30 minutes after application ensure that dogs cannot lick the product from application sites on themselves or other treated animals. • Children should not come in contact with application sites for two (2) hours after application. (See Contraindications, Warnings, Human Warnings, and Adverse Reactions, for more information) OUR CAUTION: Federal (U.S.A.) Law restricts this drug to use by or on the order of a licensed veterinarian. AUTHORS INDICATIONS: CORAXIS is indicated for the prevention of heartworm disease caused by Dirofilaria immitis. CORAXIS is also indicated for the treatment and control of the following intestinal parasites: Intestinal Stage Intestinal Parasite Adult Immature Adult Fourth Stage Larvae Hookworm Ancylostoma caninum X X X , BVMS, MS, MRCVS, DACVIM Species Uncinaria stenocephala X X X JULIE ALLEN Roundworm Toxocara canis X X (SAIM), DACVP, is a clinical assistant professor of Species Toxascaris leonina X Whipworm Trichuris vulpis X clinical pathology at Cornell University. She earned CONTRAINDICATIONS: Do not administer this product orally. (See WARNINGS.) her veterinary degree from University of Glasgow Do not use this product (containing 2.5% moxidectin) on cats. HUMAN WARNINGS: and her master’s degree from Iowa State University, Not for human use. Keep out of the reach of children. Children should not come in contact with application sites for two (2) hours where she completed a rotating internship in small after application. Causes eye irritation. Harmful if swallowed. Do not get in eyes or on clothing. Avoid contact with skin. Exposure to the product has been reported animal medicine and surgery and a residency in to cause headache; dizziness; and redness, burning, tingling, or numbness of the skin. Wash hands thoroughly with soap and warm water after handling. small animal internal medicine. She also completed If contact with eyes occurs, hold eyelids open and flush with copious amounts of water for 15 minutes. If eye irritation develops or persists, contact a a residency in clinical pathology at North Carolina physician. If swallowed, call poison control center or physician immediately for treatment advice. Have person sip a glass of water if able to swallow. State University. Dr. Allen focuses on cachexia/ Do not induce vomiting unless told to do so by the poison control center or physician. People with known hypersensitivity to benzyl alcohol or moxidectin anorexia, endocrinology, and hepatobiliary and should administer the product with caution. In case of allergic reaction, contact a physician. If contact with skin or clothing occurs, take off contaminated clothing. Wash skin immediately with plenty of soap and water. Call a poison pancreatic disease and has committed her career to control center or physician for treatment advice. The Safety Data Sheet (SDS) provides additional occupational safety improving the diagnosis of disease. information. For a copy of the Safety Data Sheet (SDS) or to report adverse reactions call Bayer Veterinary Services at 1-800-422-9874. For consumer differential diagnosis page 18 questions call 1-800-255-6826. PRECAUTIONS: Do not dispense dose applicator tubes without complete safety and administration information. Use with caution in sick, debilitated, or underweight animals. The safety of CORAXIS has not been established in breeding, pregnant, or lactating dogs. STEPHANIE BORNS-WEIL, DVM, DACVB, is an The safe use of CORAXIS has not been established in puppies and dogs less than 7 weeks of age or less than 3 lbs body weight. assistant professor of clinical sciences at Cummings Prior to administration of CORAXIS, dogs should be tested for existing heartworm infection. At the discretion of the veterinarian, infected dogs School of Veterinary Medicine at Tufts University, should be treated with an adulticide to remove adult heartworms. CORAXIS is not effective against adult D. immitis. (See ANIMAL SAFETY - where she is also the head of the Animal Behavior Safety Study in Heartworm-Positive Dogs.) ADVERSE REACTIONS: Clinic. Her interest is companion animal behavior, Since CORAXIS contains 2.5% moxidectin, studies that demonstrated the safe use of a topical solution containing 2.5% moxidectin + 10% with a special focus on aggression issues. imidacloprid were acceptable to demonstrate the safety of CORAXIS. Field Studies: Following treatment with a topical solution containing 2.5% case in point page 63 moxidectin + 10% imidacloprid or an active control, dog owners reported the following post-treatment reactions: Moxidectin + Imidacloprid Active Control OBSERVATION n = 128 n = 68 Pruritus 19 dogs (14.8%) 7 dogs (10.3%) Residue 9 dogs (7.0%) 5 dogs (7.4%) RENATA S. COSTA, DVM, MPhil, MANZCVS, Medicinal Odor 5 dogs (3.9%) None observed Lethargy 1 dog (0.8%) 1 dog (1.5%) GradDipEd, is an anesthesia resident at Cummings Inappetence 1 dog (0.8%) 1 dog (1.5%) Hyperactivity 1 dog (0.8%) None observed School of Veterinary Medicine at Tufts University. During a field study of a topical solution containing 2.5% moxidectin + 10% imidacloprid using 61 dogs with pre-existing flea allergy dermatitis, one (1.6%) Dr. Costa earned her DVM from Federal University dog experienced localized pruritus immediately after product application, and one investigator noted hyperkeratosis at the application site of one dog (1.6%). of Minas Gerais in Brazil. She earned her master’s Laboratory Effectiveness Studies: One dog in a laboratory effectiveness study experienced weakness, depression and unsteadiness between 6 and 9 days after degree and graduate diploma in education from and application of a topical solution containing 2.5% moxidectin + 10% imidacloprid. The signs resolved without intervention by day 10 post-application. The signs completed a specialty training program at Murdoch in this dog may have been related to peak serum levels of moxidectin, which vary between dogs, and occur between 1 and 21 days after product application. University in Australia. Dr. Costa is a member of The following clinical observations also occurred in laboratory effectiveness studies following application of a topical solution containing 2.5% moxidectin Australian and New Zealand College of Veterinary + 10% imidacloprid and may be directly attributed to the drug or may be secondary to the intestinal parasite burden or other underlying conditions in the Scientists, Veterinary Anesthesia and Analgesia dogs: diarrhea, bloody stools, vomiting, anorexia, lethargy, coughing, ocular discharge and nasal discharge. Observations at the application sites included Chapter. Her interests include locoregional anesthe- damp, stiff or greasy hair, the appearance of a white deposit on the hair, and mild erythema, which resolved without treatment within 2 to 48 hours. sia, pain management, low-stress handling, and Foreign Market Experience: Because the following events were reported voluntarily during post-approval use of the product containing 2.5% moxidectin + anesthesia of critically ill patients. 10% imidacloprid in foreign markets, it is not always possible to reliably establish a causal relationship to drug exposure. Adverse events associated with CORAXIS (2.5% moxidectin) are expected to be similar. case in point page 63 The following adverse events were reported in humans: eye irritation, allergic reactions, skin irritation, skin tingling, sore throat and chemical odor. Adverse events reported in dogs topically treated with a topical solution containing 2.5% moxidectin + 10% imidacloprid included: vomiting, diarrhea, bloody diarrhea, salivation, poor appetite, lethargy, weakness, restlessness, agitation, disorientation, ataxia, muscle tremors, seizures, panting, labored breathing, acute pulmonary edema, hives, rash, swollen face and ears, pruritus, erythema, alopecia, hot spots, local discomfort and discoloration of the hair at the application site. Accidental oral ingestion in dogs caused salivation, vomiting, muscle tremor, seizures, mydriasis, ataxia, lethargy, disorientation, agitation and poor appetite. Adverse events in cats topically treated with imidacloprid + moxidectin for dogs included application site and skin reactions, vomiting, lethargy, agitation and neurologic signs. To report a suspected adverse reaction, call 1-800-422-9874. ANIMAL SAFETY: In a controlled, double-masked, field safety study, a topical solution containing 2.5% moxidectin + 10% imidacloprid was administered to 128 dogs of various breeds, 3 months to 15 years of age, weighing 4 to 157 pounds. The moxidectin + imidacloprid topical solution was used safely in dogs concomitantly receiving ACE inhibitors, anticonvulsants, antihistamines, antimicrobials, chondroprotectants, corticosteroids, immunotherapeutics, MAO inhibitors, NSAIDs, ophthalmic medications, sympathomimetics, synthetic estrogens, thyroid hormones, and urinary acidifiers. Owners reported the following signs in their dogs after application of moxidectin + imidacloprid topical solution: pruritus, flaky/greasy residue at the treatment site, medicinal odor, lethargy, inappetence and hyperactivity. (See ADVERSE REACTIONS.) NADA # 141-417, Approved by FDA Bayer HealthCare LLC Animal Health Division P.O. Box 390, Shawnee Mission, Kansas 66201 U.S.A. LV1808 ©2018 Bayer HealthCare LLC Bayer (reg’d), the Bayer Cross (reg’d) and Coraxis™ are trademarks of Bayer. 2 cliniciansbrief.com May 2019

47836_Coraxis_LABEL_CLINICIANS BRIEF_2-75x10-875_FA.indd 1 2/14/19 2:15 PM OUR AUTHORS

ALICIA Z. KARAS, DVM, MS, DACVAA, KURSTEN PIERCE, DVM, DACVIM teaches at Cummings School of Veteri- (Cardiology), is a veterinary cardiologist nary Medicine at Tufts University, where at Colorado State University Veterinary she earned her DVM and completed a Teaching Hospital. She is pursuing a fel- residency in anesthesia. She is also the lowship in interventional cardiology and hospital director at Tufts Veterinary completed a cardiology residency at Cum- Emergency Treatment & Specialties in mings School of Veterinary Medicine at Walpole, Massachusetts. Tufts University. Dr. Pierce has authored case in point page 63 several book chapters and articles. Her interests include congenital and acquired heart disease in cats and dogs, cardiac bio- ADESOLA ODUNAYO, DVM, MS, markers, and interventional cardiology. DACVECC, is a clinical associate profes- case in point page 29 sor of emergency medicine and critical care at University of Tennessee. She earned her DVM from Oklahoma State LISA M. POHLMAN, DVM, MS, DACVP, University and completed a residency in is an associate professor and the director emergency medicine and critical care at of clinical pathology at Kansas State Uni- University of Missouri. versity. She earned her DVM from Univer- management tree page 11 sity of Guelph and her master’s degree in clinical pathology from Auburn Univer- sity, where she also completed a residency. ANTHONY PEASE, DVM, MS, DACVR, Dr. Pohlman serves as the president and is the chief veterinary medical officer for medical director of the Riley County WVC and a former president of the Ameri- Humane Society in Manhattan, Kansas, can College of Veterinary Radiology. and is an active teacher and mentor of Dr. Pease earned his DVM from Virginia- interns, residents, and veterinary and Maryland Regional College of Veterinary graduate students. She enjoys providing Medicine and completed a residency in CE in clinical pathology through speaking diagnostic imaging at Cornell University. engagements, online courses, and publica- He lectures nationally and internation- tions. Her research interests include iden- ally on diagnostic imaging. tification and characterization of disease top 5 page 56 in domestic species and improvement of clinical pathology laboratory methods. top 5 page 22 n

LOOK FOR THESE ARTICLES IN FUTURE ISSUES h Keys to Successful Management of Otitis Externa

h Step-by-Step Tooth Viability Assessment

h Cutaneous Melanoma Case

h Responsible Antimicrobial Use

h Top 5 Rehabilitative Exercises After Orthopedic Surgery

May 2019 cliniciansbrief.com 3 A FOUR-HIT WONDER w/d® MULTI-BENEFIT

Hill’s® Prescription Diet® w/d® is now w/d® Multi-Benefit. It’s the same nutrition trusted for multiple conditions — now with a new name and improved taste that strikes just the right chord. NEW NAME

1 Helps minimize blood glucose fluctuation, which mayreduce insulin dosage 2 Shown to address fiber-responsive GI conditions such as colitis, diarrhea or constipation

3 Helps trigger satiety and give dogs a feeling of fullness to maintain weight

4 With S+OXSHIELD™ to promote a urinary environment that reduces the risk of developing struvite and calcium oxalate crystals

ON THE COVER

TOP 5 Top 5 Cytologic Findings in Aspirates of Enlarged Lymph Nodes Lisa M. Pohlman, DVM, MS, DACVP PG 22

MANAGEMENT TREE CASE IN POINT 11 Snake Envenomation 29 Respiratory Distress Adesola Odunayo, DVM, MS, DACVECC & Inappetence in a Border Collie DIFFERENTIAL DIAGNOSIS Kursten Pierce, DVM, DACVIM 18 Neutropenia (Cardiology) Julie Allen, BVMS, MS, MRCVS, DACVIM (SAIM), DACVP TOP 5 56 Top 5 Radiographic Variants Anthony Pease, DVM, MS, DACVR

CASE IN POINT 63 Chill Protocol to Manage Aggressive & Fearful Dogs Renata S. Costa, DVM, MPhil, MANZCVS, GradDipEd Alicia Z. Karas, DVM, MS, DACVAA Stephanie Borns-Weil, DVM, DACVB

May 2019 cliniciansbrief.com 5 Make the move to clinically proven joint mobility support

Signifi cantly different joint mobility scores versus placebo In a double-blinded, placebo-controlled clinical study, client-observed joint mobility scores were signifi cantly different on Day 84 in the MOVOFLEX® Soft Chews group versus the placebo group1 Easy to administer In a survey of 500+ pet owners, 97% of owners ranked MOVOFLEX Soft Chews as easy to administer2 Contains a proprietary blend of 5 ingredients These ingredients work together to protect against free radicals and to support healthy bones, fl exibility, joints, and connective tissues

® ZANTHIN Boswellia serrata Proprietary Vitamin D3 Natural astaxanthin hyaluronic acid BIOVAFLEX® Egg shell membrane

Important Safety Information for MOVOFLEX® Soft Chews: Warnings: For animal use only. Keep out of the reach of children and animals. In case of accidental overdose, contact a health professional immediately. Cautions: Safe use in pregnant animals or animals intended for breeding has not been proven. If animal’s condition worsens or does not improve, stop product administration and consult your veterinarian.

References: 1. Muller C, Enomoto M, Steiner J, Lascelles D. Randomized pilot trial of the effects of an egg-shell membrane-based supplement (MOVOFLEX™) on mobility and serum biomarkers of inﬂ ammation in dogs with osteoarthritis. In: Proceedings from the Veterinary Orthopedic Society; March 10–17, 2018; Snowmass Village, CO. Abstract 3568. 2. Data on ﬁ le, MOVOFLEX Soft Chews Experience Program evaluation, 2016. Virbac Corporation.

© 2019 Virbac Corporation. All Rights Reserved. MOVOFLEX is a registered trademark of Virbac Corporation. BIOVAFLEX is a registered trademark of Biova, LLC, used under license. ZANTHIN is a registered trademark of U.S. Nutraceuticals, LLC, used under license. 5/19 38847 ON THE WEB

THIS MONTH’S CLINICAL FEATURES AVAILABLE ONLY ONLINE

IMAGE QUIZ Abnormal Canine Stifle Radiographs Ryan King, DVM, DACVR Stacie Aarsvold, DVM, DACVR brief.vet/stifle-rads

NOTICE OF CORRECTION In the quiz “Brain Tumors in Dogs & Cats,” promoted in the April issue and published on cliniciansbrief.com, an incorrect video appeared in question 1. The video has been replaced and the quiz corrected. Clinician’s Brief regrets the error. brief.vet/brain-tumor

SYMPOSIUM CAPSULES GET SOCIAL 15 Preview: Chicago Vet 2019 66 Currently on Clinician’s Brief social media FROM PAGE TO PATIENT 37 Tips and techniques from PRACTICE HOTLINE the research pages 67 The latest in products and services

OUR ADVERTISERS 02 AUTHORS 71 INDEX QUIZ CORNER 72 Test your knowledge

May 2019 cliniciansbrief.com 7 chewables CAUTION: Federal (U.S.A.) law restricts this drug to use by or on the order of a licensed veterinarian. INDICATIONS: For use in dogs to prevent canine heartworm disease by eliminating the tissue stage of heartworm larvae (Diroﬁlaria immitis) for a month (30 days) after infection and for the treatment and control of ascarids (Toxocara canis, Toxascaris leonina) and hookworms (Ancylostoma caninum, Uncinaria stenocephala, Ancylostoma braziliense). DOSAGE: HEARTGARD® Plus (ivermectin/pyrantel) should be administered orally at monthly intervals at the recommended minimum dose level of 6 mcg of ivermectin per kilogram (2.72 mcg/lb) and 5 mg of pyrantel (as pamoate salt) per kg (2.27 mg/lb) of body weight. The recommended dosing schedule for prevention of canine heartworm disease and for the treatment and control of ascarids and hookworms is as follows:

Color Coding 0n Dog Chewables Ivermectin Pyrantel Foil Backing Weight Per Month Content Content and Carton Up to 25 lb 1 68 mcg 57 mg Blue 26 to 50 lb 1 136 mcg 114 mg Green Introducing the 51 to 100 lb 1 272 mcg 227 mg Brown

HEARTGARD Plus is recommended for dogs 6 weeks of age and older. New Clinician’s Brief For dogs over 100 lb use the appropriate combination of these chewables. ADMINISTRATION: Remove only one chewable at a time from the foil-backed blister card. Return the card with the remaining chewables to its box to protect the product from light. Because most dogs find HEARTGARD Plus palatable, CE Platform the product can be offered to the dog by hand. Alternatively, it may be added intact to a small amount of dog food. The chewable 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 for a few minutes after administration to ensure that part of the dose is not lost or rejected. If it is suspected that any of the Get affordable, RACE-approved dose has been lost, redosing is recommended. HEARTGARD Plus should be given at monthly intervals during the period of the year when mosquitoes (vectors), potentially carrying infective heartworm larvae, are active. The initial dose must be given within a month (30 days) CE from the Clinician’s Brief after the dog’s first exposure to mosquitoes. The final dose must be given within a month (30 days) after the dog’s last exposure to mosquitoes. When replacing another heartworm preventive product in a heartworm disease preventive program, the first dose of content you trust—without ever HEARTGARD Plus must be given within a month (30 days) of the last dose of the former medication. If the interval between doses exceeds a month (30 days), the efficacy of ivermectin can be reduced. Therefore, for optimal performance, the chewable must be given once a month on or about the same day of the month. If treatment leaving your desk. is delayed, whether by a few days or many, immediate treatment with HEARTGARD Plus and resumption of the recommended dosing regimen will minimize the opportunity for the development of adult heartworms. Monthly treatment with HEARTGARD Plus also provides effective treatment and control of ascarids (T. canis, T. leonina) and hookworms (A. caninum, U. stenocephala, A. braziliense). Clients should be advised of measures to be The Clinician’s Brief CE platform offers a taken to prevent reinfection with intestinal parasites. EFFICACY: HEARTGARD Plus Chewables, given orally using the recommended dose and regimen, are effective against personalized dashboard to keep track of the tissue larval stage of D.immitis for a month (30 days) after infection and, as a result, prevent the development of the adult stage. HEARTGARD Plus Chewables are also effective against canine ascarids (T. canis, T. leonina) and lesson progress, earned hours, receipts, and hookworms (A. caninum, U. stenocephala, A. braziliense). ACCEPTABILITY: In acceptability and field trials, HEARTGARD Plus was shown to be an acceptable oral dosage form certificates and to view the latest available that was consumed at first offering by the majority of dogs. PRECAUTIONS: All dogs should be tested for existing heartworm infection before starting treatment with HEARTGARD Plus which is not effective against adult D. immitis. Infected dogs must be treated to remove adult courses. Current lesson topics include heartworms and microfilariae before initiating a program with HEARTGARD Plus. While some microfilariae may be killed by the ivermectin in HEARTGARD Plus at the recommended dose level, lymphoma, diagnosing and managing HEARTGARD Plus is not effective for microfilariae clearance. A mild hypersensitivity-type reaction, presumably due to dead or dying microfilariae and particularly involving a transient diarrhea, has been observed in clinical trials with hyperadrenocorticism, and nasal discharge ivermectin alone after treatment of some dogs that have circulating microfilariae. Keep this and all drugs out of the reach of children. and nasal planum disease. Each CE lesson In case of ingestion by humans, clients should be advised to contact a physician immediately. Physicians may contact a Poison Control Center for advice concerning cases of ingestion by humans. includes articles, videos, or webinars on a Store between 68°F - 77°F (20°C - 25°C). Excursions between 59°F - 86°F (15°C - 30°C) are permitted. Protect product from light. particular topic, from cardiology to client ADVERSE REACTIONS: In clinical field trials with HEARTGARD Plus, vomiting or diarrhea within 24 hours of dosing was rarely observed (1.1% of administered doses). The following adverse reactions have been reported following the use of HEARTGARD: Depression/lethargy, vomiting, anorexia, diarrhea, mydriasis, ataxia, staggering, communication. convulsions and hypersalivation. SAFETY: HEARTGARD Plus has been shown to be bioequivalent to HEARTGARD, with respect to the bioavailability of ivermectin. The dose regimens of HEARTGARD Plus and HEARTGARD are the same with regard to ivermectin (6 mcg/kg). Studies with ivermectin indicate that certain dogs of the Collie breed are more sensitive to the effects of Scan the QR code or visit ivermectin administered at elevated dose levels (more than 16 times the target use level) than dogs of other breeds. At elevated doses, sensitive dogs showed adverse reactions which included mydriasis, depression, ataxia, tremors, drooling, paresis, recumbency, excitability, stupor, coma and death. HEARTGARD demonstrated no signs of toxicity at cliniciansbrief.com/ce to create 10 times the recommended dose (60 mcg/kg) in sensitive Collies. Results of these trials and bioequivalency studies, support the safety of HEARTGARD products in dogs, including Collies, when used as recommended. your dashboard and start HEARTGARD Plus has shown a wide margin of safety at the recommended dose level in dogs, including pregnant or breeding bitches, stud dogs and puppies aged 6 or more weeks. In clinical trials, many commonly used flea earning CE today! collars, dips, shampoos, anthelmintics, antibiotics, vaccines and steroid preparations have been administered with HEARTGARD Plus in a heartworm disease prevention program. In one trial, where some pups had parvovirus, there was a marginal reduction in efficacy against intestinal nematodes, Using QR codes from your mobile device is easy possibly due to a change in intestinal transit time. and quick! HOW SUPPLIED: HEARTGARD Plus is available in three dosage strengths (See DOSAGE section) for dogs of different weights. Each strength comes in convenient cartons of 6 and 12 chewables. Simply focus your phone’s camera on the QR For customer service, please contact Merial at 1-888-637-4251. code as if taking a picture (but don’t click!). A ®HEARTGARD and the Dog & Hand logo are registered trademarks of Merial. notification banner will pop up at the top of your ©2015 Merial, Inc., Duluth, GA. All rights reserved. screen; tap the banner to view the linked content. THE PROTECTION DOGS COME RUNNING FOR.

The only Real-Beef Chewable isn’t just the #1 choice of dogs,1 owners,2 and veterinarians3 - it’s the one dogs look forward to. HEARTGARD Plus: 3 Protects dogs from heartworm disease and treats and controls 3 species of hookworms and two species of roundworms 3 Is approved for puppies as young as 6 weeks of age 3 Over 30 years of trusted prevention

1 Freedom of Information: 2 Data on file at 3 Data on file at NADA140-971 (January Boehringer Ingelheim. Boehringer Ingelheim. 15, 1993). IMPORTANT SAFETY INFORMATION: HEARTGARD® Plus (ivermectin/pyrantel) is HEARTGARD® and the Dog & Hand logo® are well tolerated. All dogs should be tested for heartworm infection before starting registered trademarks of Boehringer Ingelheim a preventive program. Following the use of HEARTGARD Plus, digestive and Animal Health USA Inc. ©2019 Boehringer Ingelheim Animal Health USA, Inc., Duluth, GA. neurological side effects have rarely been reported. For more information, please All rights reserved. PET-1309-HGD0319. see full prescribing information or visit www.HEARTGARD.com. See page 8 for product information summary.

xhg313368_TVP_HG-ComeRunningAd-8.125x10.875_rsg.indd 1 2/6/19 3:29 PM NO TIME TO WASTE WHEN CARE IS CRITICAL

NUTRITIONAL SUPPORT CAN SPEED UP RECOVERY AND IMPROVE PATIENT OUTCOMES* Introducing the most comprehensive range of liquid diets designed for tube feeding.

EASY TO USE INNOVATIVE CAP DESIGN CRITICAL NUTRITION Start feeding in less than a minute— Specialized cap for quick and Also includes EPA+DHA no mixing, reconstituting or easy syringe withdrawal and usage and an antioxidant complex blenderizing for NE and NG tubes

*Brunetto MA et al. Effects of nutritional support on hospital outcome in dogs and cats. J Vet Emerg Crit Care. 2010; 20: 224–231. Mohr AJ et at. Effect of early enteral nutrition on intestinal permeability, intestinal protein loss, and outcome in dogs with severe parvoviral enteritis. J Vet Int Med. 2003; 17: 791–798.

SNAKE ENVENOMATION

Adesola Odunayo, DVM, MS, DACVECC University of Tennessee

SNAKEBITE VICTIM PRESENTED

Snake seen and/or identifiable?

YES NO

Snake venomous?*

YES NO

Perform triage examination TREATMENT h Evaluate airway, h Analgesia respiration, circulation, h Anti-inflammatory medications; NSAIDs are acceptable in blood pressure, and PCV/ patients with nonvenomous snakebites TS/glucose/lactate, and h Cage rest perform ECG1 h Antibiotics are generally only indicated in cases of infection; h Provide analgesia (eg, culture and susceptibility testing may be of benefit if indicated opioids); NSAIDs should be avoided, as many venoms can lead to coagulopathy, hypotension, and pigmenturia1,2 h If necessary, administer Determine whether patient is stable or unstable based diphenhydramine or on physical examination abnormalities trazodone to keep patient h Stable: puncture wounds, pain, hemorrhage, calm3,4 neurologic signs, edema, bruising, tissue necrosis, h Avoid tourniquets, ice petechiae, ecchymoses1-4 packs, hot packs, h Unstable: tachycardia, weak peripheral pulses, incisions, and suction2,4 hypotension, obtundation, seizures, arrhythmias, h Limit patient activity as any findings noted for stable patients1,2,4 much as possible to slow spread of venom2,4

PATIENT STABLE PATIENT UNSTABLE

Go to Patient stable box, Go to Patient unstable next page box, page 13

*Coral snakes and pit vipers (eg, rattlesnakes, copperheads, water moccasins, cottonmouths) are among the venomous snakes found PCV = packed cell volume in the United States.2,4 TS = total solids

May 2019 cliniciansbrief.com 11 MANAGEMENT TREE h EMERGENCY MEDICINE & CRITICAL CARE h PEER REVIEWED

PATIENT STABLE

Conduct diagnostic investigation (eg, CBC, serum chemistry profile, urinalysis, ECG, blood pressure, coagulation profile) and snakebite severity score evaluation (see Suggested Reading). Diagnostic investigation findings may include: h Echinocytes (may be present for up to 24-48 hours), thrombocytopenia, and leukocytosis on CBC4-6 h Coagulation abnormalities on coagulation testing4,7,8 h Alterations in ALT, ALP, GGT, AST, creatine phosphokinase, creatinine, blood urea nitrogen, sodium, potassium, calcium, chloride, and glucose on serum chemistry profile1-6 h Pigmenturia, glucosuria, and casts on urinalysis2

Determine outpatient versus inpatient status h Consider outpatient therapy in stable patients with minimal pain and/or no clinical or blood work abnormalities (eg, thrombocytopenia, evidence of coagulopathy or hypotension) h Consider inpatient therapy in unstable patients and/or any patient with significant pain, pigmenturia, casts, elevated hepatocellular or cholestatic liver enzyme activity, azotemia, and/or hypotension4

OUTPATIENT INPATIENT

TREATMENT TREATMENT h Analgesia (eg, buprenorphine, h Fluid therapy to treat hypovolemia and dehydration and provide daily gabapentin, fentanyl patch) maintenance fluid requirement h Shaving and cleaning area around h Antivenom, if indications (eg, hypotension, neurologic signs, coagulopathy, puncture wounds, if able tissue necrosis, rapid progression of swelling; see Antivenom h Providing specific monitoring Recommendations) persist10,12 instructions to the pet owner h Analgesia (ie, opioids); NSAIDs should be avoided1,2,4 h Antibiotics are indicated only in h Shaving and cleaning area around puncture wounds, if able patients with evidence of an h Hyperbaric oxygen treatment,13,14 if available infected wound2,9 h Long-term antiepileptic medications (eg, levetiracetam) in patients with seizures h Glucocorticoids are controversial h Packed RBC transfusion in bleeding anemic patients and typically not recommended2,4,10 h Passive range of motion and frequent changes in recumbency in patients with h The efficacy of the rattlesnake muscle weakness and/or paralysis vaccine is controversial and not h Mechanical ventilation in patients with upper airway obstruction and/or indicated in the immediate hypoventilation1,5 treatment of a snakebite5,11 h Antibiotics are indicated only in patients with evidence of an infected wound2,9 h Glucocorticoids are controversial and typically not recommended2,4,10

Consider outpatient therapy when patient is clinically stable (eg, pain is under control, patient has interest in food, wounds are clinically static)

ALP = alkaline phosphatase ALT = alanine transaminase AST = aspartate aminotransferase GGT = gamma-glutamyl transferase

12 cliniciansbrief.com May 2019 PATIENT UNSTABLE

TREATMENT Address life-threatening abnormalities h Fluid bolus of isotonic crystalloids (10-25 mL/kg over 15 minutes) in patients with hypotension, then reassessment of patient.15 Vasopressors may be required in certain patients h Benzodiazepines in patients with active seizures h Analgesia (ie, opioids); NSAIDs should be avoided1,2,4 h Antivenom (see Antivenom Recommendations)2,11 h Antiarrhythmics (eg, lidocaine, procainamide, amiodarone) as needed h Oxygen supplementation as needed10 h Intubation and mechanical ventilation in patients with airway obstruction and/or hypoventilation1,5 h Vasopressors in patients with hypotension unresponsive to fluid therapy

After patient is stable, go to Patient stable box

References 1. Mcalees TJ, Abraham LA. Australian elapid snake envenomation in cats: clinical priorities ANTIVENOM RECOMMENDATIONS and approach. J Feline Med Surg. 2017;19(11):1131-1147. 2. Armentano RA, Schaer M. Overview and controversies in the medical management of pit h Clinicians should start with one vial of antivenom viper envenomation in the dog. J Vet Emerg Crit Care (San Antonio). 2011;21(5):461-470. per patient; however, patients with a lower 3. McCown JL, Cooke KL, Hanel RM, Jones GL, Hill RC. Effect of antivenin dose on outcome from crotalid envenomation: 218 dogs (1988-2006). J Vet Emerg Crit Care (San Antonio). 1-5 body weight may require more antivenom, as 2009;19(6):603-610. smaller patients tend to receive a larger amount 4. Gilliam LL, Brunker J. North American snake envenomation in the dog and cat. Vet Clin North Am Small Anim Pract of venom per kg of body weight when bitten (eg, . 2011;41(6):1239-1259. 5. Wells RJ, Hopper K. Management of clinical snake bite in dogs and cats. In: a Chihuahua vs a Great Dane injected with the Gopalakrishnakone P, Vogel CW, Seifert SA, Tambourgi DV, eds. Clinical Toxinology in same amount of venom).5 Australia, Europe, and Americas. Springer; 2018:487-503. 6. Goddard A, Schoeman JP, Leisewitz AL, Nagel SS, Aroch I. Clinicopathologic abnormalities h If the antivenom is lyophilized, one vial should be associated with snake envenomation in domestic animals. Vet Clin Pathol. 2011;40(3):282-292. 5 7. Stanley MK. Viscoelastic Coagulation Changes in Dogs with Tiger Snake Envenomation reconstituted with crystalloid fluids (100-250 mL). [master’s thesis]. Melbourne: University of Melbourne; 2018. h 8. Lieblick BA, Bergman PJ, Peterson NW. Thromboelastographic evaluation of dogs bitten by Antivenom should be administered rattlesnakes native to southern California. Am J Vet Res. 2018;79(5):532-537. 2,3 intravenously over 1 to 2 hours. 9. Carr A, Schultz J. Prospective evaluation of the incidence of wound infection in rattlesnake envenomation in dogs. J Vet Emerg Crit Care (San Antonio). 2015;25(4):546-551. h Patients should be monitored for signs of 10. Hoose JA, Carr A. Retrospective analysis of clinical findings and outcome of cats with anaphylactoid/anaphylactic reactions. suspected rattlesnake envenomation in southern California: 18 cases (2007-2010). J Vet Emerg Crit Care (San Antonio). 2013;23(3):314-320. h Diphenhydramine may be considered if 11. Witsil AJ, Wells RJ, Woods C, Rao S. 272 cases of rattlesnake envenomation in dogs: demographics and treatment including safety of F(ab’)2 antivenom use in 236 patients. anaphylaxis or a mild anaphylactoid reaction to Toxicon. 2015;105:19-26. the antivenom is suspected, whereas epinephrine 12. Pashmakova MB, Bishop MA, Black DM, et al. Multicenter evaluation of the administration of J Am Vet Med Assoc and intravenous fluids should be administered for crotalid antivenom in cats: 115 cases (2000-2011). . 2013;243(4):520-525. 13. Birnie GL, Fry DR, Best MP. Safety and tolerability of hyperbaric oxygen therapy in cats and 2 severe anaphylaxis/anaphylactoid reactions. dogs. J Am Anim Hosp Assoc. 2018;54(4):188-194. Administration of antivenom should be stopped in 14. Korambayil PM, Ambookan PV, Abraham SV, Ambalakat A. A multidisciplinary approach 4 with hyperbaric oxygen therapy improve outcome in snake bite injuries. Toxicol Int. both instances. However, if the reaction is not 2015;22(1):104-109. severe, administration of antivenom should be 15. Odunayo A. Fluid therapy. Clinician’s Brief. 2018;16(10):71-75. slowly resumed after approximately 20 to 60 minutes.4 Additional support in patients with Suggested Reading hypotension (eg, vasopressors) and/or respiratory Peterson ME, Matz M, Seibold K, Plunkett S, Johnson S, Fitzgerald K. A randomized multicenter 1 trial of Crotalidae polyvalent immune F(ab) antivenom for the treatment of rattlesnake signs (eg, mechanical ventilation) may be required. envenomation in dogs. J Vet Emerg Crit Care (San Antonio). 2011;21(4):335-345.

May 2019 cliniciansbrief.com 13 ACP™ Double-Syringe System Autologous Conditioned Plasma The ACP System allows for rapid and efficient concentration of platelets and growth factors from autologous blood for use on soft-tissue injuries.

Features and Benefits: ■Requires only 15 mL of patient’s blood, simplifying blood recovery from the patient ■In vitro research has shown statistically improved tenocyte, chondrocyte, and osteoblast proliferation when cultured with ACP vs controls1 ■The ACP System does not concentrate inflammatory white or red blood cells, which can negatively interfere with the healing process2,3

References 1. Arthrex, Inc. LA0815A. Naples, FL; 2010. 2. Scott A, Khan KM, Roberts CR, Cook JL, Duronio V. What do we mean by the term “inflammation“? A contemporary basic science update for sports medicine. Br J Sports Med. 2004;38(3):372-380. doi:10.1136/bjsm.2004.011312. 3. Jiang N, Tan NS, Ho B, Ding JL. Respiratory protein-generated reactive oxygen species as an antimicrobial strategy. Nat Immunol. 2007;8(10):1114-1122. doi:10.1038/ni1501. Simplified Preparation Steps

1 2 3 4 Draw 15 mL of patient‘s For equine and canine, run the Transfer the ACP to the inner Unscrew the blood. centrifuge at 1500 rpm syringe by pushing down on the inner syringe for 5 minutes. outer syringe and pulling the and apply ACP inner plunger up. to treatment site.

Arthrex ACP Other PRP Systems Volume of patient blood drawn 15 mL 60 mL-120 mL Centrifugation steps 1× 1-2× Centrifugation time 5 min 15-30 min For more information, go to ArthrexVetSystems.com Does it concentrate red and white No: reduces Yes: concentrates or call 1-888-215-3740 blood cells? © 2018 Arthrex, Inc. All rights reserved. Can be clotted prior to surgical delivery? Yes Yes VAD1-00208-EN_D SYMPOSIUM CAPSULES SYMPOSIUM CAPSULES

atopic patients carries many benefits; Atopic Dermatitis anecdotally, it is not possible to overbathe an atopic dog. Shampoos with antiseptic and Preview: Treatment epidermal restoration effects should be used; Chicago Vet 2019 Recommendations the choice of antimicrobial shampoo should be based on the type of infection(s) in the individual patient. May 13-16, 2019 Chicago, Illinois Atopic dermatitis is a common dermatologic Treatment options for managing ongoing problem in pets. In 2010, the International pruritus include corticosteroids, oclacitinib, Committee on Allergic Diseases of Animals IL-31 monoclonal antibodies, and cyclosporine. developed guidelines for a multifaceted The short- and long-term benefits and side approach to managing atopic patients, which effects of each option should be discussed included treatment of acute flares, identifica- with the owner. Some patients may benefit tion and avoidance of flare triggers, improve- from a combination of therapies; the ment of skin and coat hygiene, drug therapy best balance between efficacy and safety to treat ongoing pruritus, and allergen- should be implemented. Allergen-specific specific immunotherapy when feasible.1 immunotherapy (injectable or sublingual) may be the only effective nondrug therapy Many treatment and supportive care options that may address the patient’s immune are available and are often combined for dysfunction directly, potentially leading to a synergistic effects, an important concept cure. Immunotherapy should be considered in to convey to owners. Supportive therapies atopic patients, particularly young-to-middle– include antihistamines, essential fatty acids, aged patients that may otherwise be expected bathing, restoration of the epidermal barrier, to receive lifelong drug therapy.—Lewis TP control of secondary infections, and, if indicated, topical anti-inflammatory therapy. Reference Essential fatty acids and antihistamines are 1. Olivry T, DeBoer DJ, Favrot C, et al. Treatment of canine atopic dermatitis: 2015 updated guidelines inadequate as single therapy agents, except from the International Committee on Allergic Diseases in patients with mild clinical signs. Bathing of Animals (ICADA). BMC Vet Res. 2015;11:210

SAVE THE DATE Allergen-specific immunotherapy (injectable or sublingual) may be the Chicago Vet 2020 only effective nondrug therapy that may address the patient’s immune May 13-15, 2020 Chicago, Illinois dysfunction directly, potentially leading to a cure.

May 2019 cliniciansbrief.com 15 SYMPOSIUM CAPSULES

In cats, lymphoma affects the small of EATL type I is typically more straight- Gastrointestinal intestines 4 times more often than the forward than EATL type II, as intestinal large intestines. There are 2 types of thickening in EATL type II can be similar Lymphoma in enteropathy-associated T-cell lym- to that of inflammatory bowel disease Cats phoma (EATL); type I is a high-grade and typically requires abdominal ultra- lymphoblastic lymphoma composed sonography and histopathology to con- of intermediate-to-large B cells and firm diagnosis. Lymphoma commonly affects the GI tract often a palpable mass, whereas type II and accounts for 30% of all feline cancers is a low-grade lymphocytic lymphoma Cats generally tolerate chemother- and 55% of feline GI tumors. Male cats are composed of small cells (most com- apy well (better than dogs) and show predisposed, whereas intact female cats monly, T cells) that occurs more dif- improved quality of life. Neutropenia are at decreased risk. Median age of onset fusely throughout the GI tract. Weight rarely occurs. Prognosis for GI lym- is 11 years. FeLV and FIV play direct and loss, vomiting, diarrhea, and anorexia phoma is variable; median survival time indirect roles, respectively, in the devel- are common, with signs developing following CHOP-based treatment pro- opment of lymphoma. There is increasing over several months in EATL type II tocols for EATL type I is 4 to 6 months. evidence of a link between chronic GI cases or several days to weeks in EATL Less aggressive protocols (eg, chlo- inflammation and lymphoma. Changes type I cases. Vomiting is often consid- rambucil, prednisolone) are typically in feline diets have also been suspected ered normal by cat owners, who may adequate for EATL type II, with median to play a part in the increase in GI lym- attribute it to hairballs or eating too survival times of more than 2 years. phoma in cats over the last 20 years, quickly, but this clinical sign should not Because inflammation appears to play although further studies are needed. be ignored by clinicians. Icterus may be a role in EATL type II, novel protein Environmental tobacco smoke exposure seen with either lymphoma type but is diets, probiotics, and B12 supplementa- reportedly increases risk for lymphoma. more common in EATL type I. Diagnosis tion may be indicated.—Ettinger S

Team members should treat owner should always be used first. Before giv- Mapping the interactions regarding euthanasia with ing the intravenous injection, clinicians Euthanasia the utmost care and empathy. On the should advise the owner how quickly appointed day, everything should be the pet will pass. Encouraging owners to Experience ready when the owner and pet arrive, speak to their pet while the euthanasia including paperwork placed in the solution is being administered keeps their examination room; the owner and focus away from the injection. Clinicians Euthanasia is emotionally challenging for pet should be helped immediately to should consider listening silently while the veterinary team. When approaching a the designated room, which should the heart stops to honor the moment, euthanasia appointment, team members be warm and comfortable. Clinicians then stay for a few minutes to watch for should consider what they would do for should preferably stay in the room until agonal breaths or movement. When exit- their own pet and use that as the mini- the euthanasia is complete and should ing, the clinician can hand the owner a mum standard of care for the patient and not pass judgment or appear uncom- wireless doorbell for the owner to use to owner. Clinicians should be the first to fortable about the owner’s decision. signal when he or she is ready to leave; broach the subject of euthanasia; owners the owner should not have to leave the may be reluctant to bring it up and, even Euthanasia should be explained to own- pet alone in the room. A paw print can if initially upset by it, will understand that ers as a gentle process in which the pet be made using air-drying clay and given they have been given permission to con- goes to sleep and does not wake up. at the appointment before the owner sider it as the next step. Intramuscular or subcutaneous sedation leaves.—Gardner M

16 cliniciansbrief.com May 2019 nurse team maintain a good relationship, and the practice may be illuminating and Civil Wars: as solid teamwork is key to a successful help team members connect with each practice. Handling stress starts with self- other. Cross-training between teams can Front vs Back care; exhaustion, stress, and burnout lead to greater understanding of the roles may be challenges faced in a culture of other team members play, and employ- guilt that values overwork. ees should be encouraged to help each Communication, leadership, and conflict other. resolution are important skills for the vet- Team members not completing duties as erinary team to create a successful and asked, gossiping, and managers assign- Owner satisfaction is a team effort. It positive workplace. Understanding one’s ing tasks and resources unfairly can is important to create a culture that own personality type is critical to effec- cause conflict in practice. Team members appreciates and empathizes with own- tive communication. Negative emotional should attempt to resolve conflicts with- ers. Avoiding complaining and gossiping reactions (eg, anger, fear) are inevitable, out involving managers. Self-awareness, helps create a happier, positive work- but being able to recognize and control understanding, and finding common place. Good communication requires these reactions can be helpful. Having ground are key to conflict resolution. study, practice, and commitment to empathy, which involves viewing a sit- Discussing the core values of employees continuing education.—Brashear M n uation from another person’s perspec- tive, and always assuming good intent of others are likewise important for the veterinary team. These skills can help the client services team and the veterinary Owner satisfaction is a team effort.

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May 2019 cliniciansbrief.com 17 DIFFERENTIAL DIAGNOSIS h INTERNAL MEDICINE/CLINICAL PATHOLOGY h PEER REVIEWED

Neutropenia

Julie Allen, BVMS, MS, MRCVS, DACVIM (SAIM), DACVP Cornell University

•

FOR MORE Following are differential diagnoses, listed in order of likelihood, Find more Differential Diagnosis lists in for patients presented with neutropenia. upcoming issues of Clinician’s Brief and on h Increased migration into tissue due to severe • Hemophagocytic syndrome, often with cliniciansbrief.com inflammation (eg, pneumonia, peritonitis) other cytopenias or acute endotoxemia due to increased • Histiocytic sarcoma, often with other h Panting margination; can occur within an hour of cytopenias h Hypercholesterolemia endotoxin release by gram-negative bacteria • Drugs h Hypocholesterolemia h Decreased bone marrow production (often in • Toxins h Hypoalbuminemia association with other cytopenias) resulting • Viruses h Decreased Total from: h Vitamin B12 deficiency, particularly in border Thyroxine • Chemotherapeutics collies, Australian shepherd dogs, giant h Increased Total • Estrogen toxicity (endogenous [eg, Sertoli schnauzers, and beagles Thyroxine cell tumor] vs exogenous) h Breed-associated cause of unknown mecha- h Hypoglycemia h Epistaxis • Other drugs (eg, potentiated sulfonamides) nism, particularly in Belgian Tervurens and h Regurgitation • Myelophthisis Australian shepherd dogs – Myelofibrosis h Idiopathic neutropenia (cats) n – Neoplasia (eg, lymphoblastic leukemia, multiple myeloma) References • Bone marrow necrosis (eg, from sepsis, Brown MR, Rogers KS. Neutropenia in dogs and cats: a retrospective study of 261 cases. J Am Anim Hosp Assoc. heatstroke, or drugs [eg, phenobarbital, 2001;37(2):131-139. carprofen, metronidazole, cyclophospha- Devine L, Armstrong PJ, Whittemore JC, et al. Presumed primary immune-mediated neutropenia in 35 dogs: a ret- mide, colchicine, fenbendazole]) rospective study. J Small Anim Pract. 2017;58(6):307-313. • Canine parvovirus and feline panleukope- Latimer KL, Prasse KW. Leukocytes. In: Latimer KS, Mahaffey EA, Prasse KW, eds. Duncan and Prasse’s Veterinary nia virus Laboratory Medicine: Clinical Pathology. 4th ed. Ames, IA: Blackwell Publishing Professional; 2003:45-82. • FeLV and FIV Schnelle AN, Barger AM. Neutropenia in dogs and cats: causes • Tick-borne disease (eg, Ehrlichia canis, and consequences. Vet Clin North Am Small Anim Pract. 2012;42(1):111-122. E ewingii, Anaplasma phagocytophilum, Schultze AE. Interpretation of canine leukocyte responses. babesiosis) In: Weiss DJ, Wardrop KJ, eds. Schalm’s Veterinary Hematology. 6th ed. Ames, IA: Blackwell Publishing Ltd; • Gray collie syndrome (ie, cyclic 2010:321-334. hematopoiesis) Soare T, Noble PJ, Hetzel U, Fonfara S, Kipar A. Paraneoplastic syndrome in haemophagocytic histiocytic sarcoma in a • Trapped neutrophil syndrome of border dog. J Comp Pathol. 2012;146(2-3):168-174. collies Stockham SL, Scott MA. Leukocytes. In: Stockham SL, Scott MA. Fundamentals of Veterinary Clinical Pathology. 2nd h Increased neutrophil destruction resulting ed. Ames, IA: Blackwell Publishing; 2008:53-106. from: Suwa A, Shimoda T. Lymphoma-associated hemophagocytic syndrome in six dogs. J Vet Med Sci. 2018;80(8):1271-1276. • Immune-mediated neutropenia (primary or secondary [eg, to drugs or infection])

18 cliniciansbrief.com May 2019 2 tasty options With added Great protection, flea prevention great value

The dogs have spoken.

Heartworm infection is Give your clients the bacon-ﬂ avored parasite protection they need, with: 1 on the rise and many dogs SENTINEL® SPECTRUM® Chews IVERHART MAX® Soft Chew are going unprotected. (milbemycin oxime/lufenuron/praziquantel) (ivermectin/pyrantel pamoate/praziquantel)

To order both tasty options for your clinic, contact your Virbac representative at 1-844-4-VIRBAC (1-844-484-7222).

Important Safety Information for SENTINEL® SPECTRUM® Chews (milbemycin oxime/lufenuron/praziquantel): Dogs should be tested for heartworm infection prior to use. Mild hypersensitivity reactions have been noted in some dogs carrying a high number of circulating microﬁ lariae. Treatment with fewer than 6 monthly doses after the last exposure to mosquitoes may not provide complete heartworm prevention. For complete product information, refer to the product insert. To obtain a product insert, contact Veterinary Technical Product Support at 1-800-338-3659, or visit us.virbac.com. Important Safety Information for IVERHART MAX® Soft Chew (ivermectin/pyrantel pamoate/praziquantel): All dogs should be tested for existing heartworm infection before starting treatment with IVERHART MAX Soft Chew. Use with caution in sick, debilitated, or underweight dogs weighing less than 10 lb. Gastrointestinal and neurological signs, such as convulsions, have been reported following the use of ivermectin products. For complete product information, refer to the product insert. To obtain a product insert, contact Veterinary Technical Product Support at 1-800-338-3659, or visit us.virbac.com. For complete product information, please see pages 20 and 21.

Reference: 1. AHS announces ﬁ ndings of new heartworm incidence survey. American Heartworm Society website. https://heartwormsociety.org/newsroom/in-the-news/347-ahs-announces-ﬁ ndings-of-new-heartworm-incidence-survey. Accessed January 17, 2019.

© 2019 Virbac Corporation. All Rights Reserved. SENTINEL, SPECTRUM, and IVERHART MAX are registered trademarks of Virbac Corporation. 5/19 36897 Intestinal Nematode and Cestode Treatment and Control: Dogs may In a second margin of safety study, 64 six-week-old puppies (16 per be exposed to and can become infected with roundworms, whipworms, group) were dosed with either a sham (0X) or 1, 3, or 5X the maximum hookworms, and tapeworms throughout the year, regardless of season exposure dose of SENTINEL SPECTRUM Chews on days 1, 15, 29, and or climate. Clients should be advised of appropriate measures to prevent 43. A dose dependent increase in ataxia, decreased activity, tremors, and reinfection of their dog with intestinal parasites. Because the prepatent salivation was seen within 24 hours of treatment. Splayed hind limbs period for E. multilocularis may be as short as 26 days, dogs treated at were observed once in one dog in the 5X treatment group. Vomiting was the labeled monthly intervals may become reinfected and shed eggs observed in the 5X treatment group. between treatments. For SENTINEL SPECTRUM Chews, the maximum exposure based on Contraindications: There are no known contraindications to the use of product dosing is 2.5 mg/kg for milbemycin oxime, 50.7 mg/kg for SENTINEL SPECTRUM Chews. lufenuron and 25.1 mg/kg for praziquantel, which is higher than the minimum effective dose used in the safety studies for milbemycin oxime Warnings: Not for use in humans. Keep this and all drugs out of the and lufenuron (see below). reach of children. Caution: Federal (USA) law restricts this drug to use by or on the order of Milbemycin Oxime: Two studies were conducted in heartworm-infected a licensed veterinarian. Precautions: Treatment with fewer than 6 monthly doses after the last dogs treated with milbemycin oxime. Mild, transient hypersensitivity exposure to mosquitoes may not provide complete heartworm prevention reactions were observed in dogs with high microfilariae counts Description: SENTINEL® SPECTRUM® Chews are available in four (see EFFECTIVENESS). (see PRECAUTIONS). strengths in color-coded packages for oral administration to dogs and puppies according to their weight. Each chewable flavored tablet is Prior to administration of SENTINEL SPECTRUM Chews, dogs should Safety studies in pregnant dogs demonstrated that doses of 0.6X the formulated to provide a minimum of 0.23 mg/pound (0.5mg/kg) of be tested for existing heartworm infections. At the discretion of the maximum exposure dose of SENTINEL SPECTRUM Chews, (1.5 mg/kg milbemycin oxime, 4.55 mg/pound (10mg/kg) of lufenuron, and veterinarian, infected dogs should be treated to remove adult heartworms. of milbemycin oxime), administered daily from mating through weaning, 2.28 mg/pound (5mg/kg) of praziquantel. SENTINEL SPECTRUM Chews are not effective against adult D. immitis. resulted in measurable concentrations of milbemycin oxime in milk. Puppies nursing these females demonstrated milbemycin oxime-related Milbemycin oxime consists of the oxime derivatives of Mild, transient hypersensitivity reactions, such as labored breathing, effects (depression, decreased activity, diarrhea, dehydration, nasal 5-didehydromilbemycins in the ratio of approximately 80% A4 vomiting, hypersalivation, and lethargy have been noted in some dogs discharge). A subsequent study, which evaluated the daily administration (C32H45NO7, MW 555.71) and 20% A3 (C31H43NO7, MW 541.68). treated with milbemycin oxime carrying a high number of circulating of 0.6X the maximum exposure dose of SENTINEL SPECTRUM Chews, Milbemycin oxime is classified as a macrocyclic anthelmintic. microfilariae. These reactions are presumably caused by release of from mating until one week before weaning, demonstrated no effects protein from dead or dying microfilariae. on the pregnant females or their litters. A study, in which pregnant Lufenuron is a benzoylphenylurea derivative with the following chemical females were dosed once, at 0.6X maximum exposure dose of composition: N-[2,5-dichloro-4-(1,1,2,3,3,3,-hexafluoropropoxy)-phenyl- Do not use in puppies less than six weeks of age. SENTINEL SPECTRUM Chews before, on the day of, or shortly after aminocarbonyl]-2,6-difluorobenzamide (C17H8CI2F8N2O3, MW 511.15). whelping, resulted in no effects on the puppies. Benzoylphenylurea compounds, including lufenuron, are classified as Do not use in dogs or puppies less than two pounds of body weight. insect development inhibitors (IDIs). Some nursing puppies, at 2, 4, and 6 weeks of age, administered oral The safety of SENTINEL® SPECTRUM® Chews has not been evaluated doses of 9.6 mg/kg milbemycin oxime (3.8X the maximum exposure dose Praziquantel is an isoquinolone anthelmintic with the chemical name in dogs used for breeding or in lactating females. Studies have of SENTINEL SPECTRUM Chews) exhibited tremors, vocalization, and 2-(Cyclohexylcarbonyl)-1,2,3,6,7,-11b-hexahydro-4H-pyrazino[2,1-a] been performed with milbemycin oxime and lufenuron alone (see ataxia. These effects were all transient and puppies returned to normal isoquinolin-4-one. ANIMAL SAFETY). within 24 to 48 hours. No effects were observed in puppies administered 0.5 mg/kg milbemycin oxime (minimum label dose). Indications: SENTINEL SPECTRUM Chews are indicated for the Adverse Reactions: The following adverse reactions have been prevention of heartworm disease caused by Dirofilaria immitis; for the reported in dogs after administration of milbemycin oxime, lufenuron, or A rising-dose safety study conducted in rough-coated Collies resulted prevention and control of flea populations Ctenocephalides( felis); and for praziquantel: vomiting, depression/lethargy, pruritus, urticaria, diarrhea, in ataxia, pyrexia, and periodic recumbency in one of fourteen dogs the treatment and control of adult roundworm (Toxocara canis, Toxascaris anorexia, skin congestion, ataxia, convulsions, salivation, and weakness. administered milbemycin oxime at 12.5 mg/kg (5X the maximum leonina), adult hookworm (Ancylostoma caninum), adult whipworm exposure dose of SENTINEL SPECTRUM Chews). Prior to receiving the (Trichuris vulpis), and adult tapeworm (Dipylidium caninum, Taenia To report suspected adverse drug events, contact Virbac at 12.5 mg/kg dose on day 56 of the study, all animals had undergone a pisiformis, Echinococcus multilocularis and Echinococcus granulosus) 1-800-338-3659 or the FDA at 1-888-FDA-VETS. dosing regimen consisting of 2.5 mg/kg milbemycin oxime on day 0, infections in dogs and puppies two pounds of body weight or greater and followed by 5.0 mg/kg on day 14, and 10.0 mg/kg on day 32. No adverse six weeks of age and older. For technical assistance, call Virbac at 1-800-338-3659. reactions were observed in any of the Collies treated with doses less than 12.5 mg/kg. Dosage and Administration: SENTINEL SPECTRUM Chews should be Information for Owner or Person Treating Animal: Echinococcus administerd orally, once every month, at the minimum dosage of multilocularis and Echinococcus granulosus are tapeworms found in wild Lufenuron: In a ten-month study, doses of lufenuron up to 2X the 0.23 mg/lb (0.5 mg/kg) milbemycin oxime, 4.55 mg/lb (10 mg/kg) canids and domestic dogs. E. multilocularis and E. granulosus can infect maximum exposure dose of SENTINEL SPECTRUM Chews (10 mg/kg) lufenuron, and 2.28 mg/lb (5 mg/kg) praziquantel. For heartworm humans and cause serious disease (alveolar hydatid disease and hydatid caused no overt toxicity. A single dose of 200 mg/kg had no marked prevention, give once monthly for at least 6 months after exposure to disease, respectively). Owners of dogs living in areas where E. multilocularis effect on adult dogs, but caused decreased activity and reduced mosquitoes (see EFFECTIVENESS). or E. granulosus are endemic should be instructed on how to minimize their appetite in eight-week-old puppies. Lufenuron tablets were evaluated risk of exposure to these parasites, as well as their dog’s risk of exposure. with concurrent administration of flea adulticides containing carbaryl, Although SENTINEL SPECTRUM Chews were 100% effective in laboratory permethrin, chlorpyriphos, and cythioate. No toxicty resulted from these studies in dogs against E. multilocularis and E. granulosus, no studies combinations. Lufenuron tablets did not cause cholinesterase inhibition have been conducted to show that the use of this product will decrease nor did they enhance cholinesterase inhibition caused by exposure to the incidence of alveolar hydatid disease or hydatid disease in humans. organophoshphates. Because the prepatent period for E. multilocularis may be as short as 26 days, dogs treated at the labeled monthly intervals may become reinfected Two laboratory and two well-controlled field studies were conducted to and shed eggs between treatments. evaluate reproductive safety of lufenuron tablets in breeding dogs. In one of the laboratory studies, in which lufenuron was administered to Beagle Effectiveness dogs as three divided doses, equivalent to 17.8X the maximum exposure Heartworm Prevention: In a well-controlled laboratory study, dose of SENTINEL SPECTRUM Chews (10 mg/kg), the ratio of gravid SENTINEL SPECTRUM Chews (milbemycin oxime, lufenuron, praziquantel) females to females mated was 8/8 or 100% in the control group and 6/9 were 100% effective against induced heartworm infections when or 67% in the lufenuron-treated group. The mean number of pups per administered once monthly for 6 consecutive months. In well-controlled litter was two animals higher in the lufenuron versus control groups and laboratory studies, neither one dose nor two consecutive doses of mean birth weights of pups from treated females in this study was lower SENTINEL SPECTRUM Chews provided 100% effectiveness against than control groups. These pups grew at a similar rate to the control To ensure adequate absorption, always administer SENTINEL SPECTRUM induced heartworm infections. pups. The incidence of nasal discharge, pulmonary congestion, diarrhea/ Chews to dogs immediately after or in conjunction with a normal meal. dehydration, and sluggishness was higher in the lufenuron-treated pup Intestinal Nematodes and Cestodes Treatment and Control: Elimination of group than in the control pup group. The incidence of these signs was SENTINEL SPECTRUM Chews may be offered to the dog by hand the adult stage of hookworm (Ancylostoma caninum), roundworm (Toxacara transient and decreasing by the end of lactation. or added to a small amount of dog food. The chewables should be canis, Toxascaris leonina), whipworm (Trichuris vulpis) and tapeworm administered in a manner that encourages the dog to chew, rather than (Dipylidium caninum, Echinococcus multilocularis, Echinococcus granulosus, Results from three additional reproductive safety studies, one laboratory to swallow without chewing. Chewables may be broken into pieces and Taenia pisiformis) infections in dogs was demonstrated in well-controlled and two field studies, evaluating eleven breeds of dogs, did not fed to dogs that normally swallow treats whole. Care should be taken laboratory studies. demonstrate any adverse findings for the reproductive parameters that the dog consumes the complete dose, and treated animals should measured, including fertility, pup birth weights, and pup clinical signs, be observed a few minutes after administration to ensure that no part of Flea Prevention and Control: In well-controlled studies, after administration of lufenuron up to 1X the maximum exposure dose of the dose is lost or rejected. If it is suspected that any of the dose has been SENTINEL SPECTRUM Chews were effective in preventing flea eggs SENTINEL SPECTRUM Chews. The average milk: blood concentration ratio lost, redosing is recommended. from hatching, thus providing control of the development of flea was approximately 60 (i.e. 60X higher drug concentrations in the milk populations (Ctenocephalides felis). compared to drug levels in the blood of treated females). Nursing puppies Heartworm Prevention: SENTINEL SPECTRUM Chews should be averaged 8-9 times higher blood concentrations of lufenuron compared administered at monthly intervals beginning within one month of the Palatability: In a field study of 117 dogs offered SENTINEL SPECTRUM to their dams. dog’s first seasonal exposure to mosquitoes and continuing until at least Chews, 113 dogs (96.6%) accepted the product when offered from the 6 months after the dog’s last seasonal exposure (see EFFECTIVENESS). hand as if a treat, 2 dogs (1.7%) accepted it from the bowl with food, 1 Storage Information: Store in a dry place at controlled room SENTINEL SPECTRUM Chews may be administered year-round dog (0.9%) accepted it when it was placed in the dog’s mouth, and 1 dog temperature, between 59° and 77°F (15-25°C). without interruption. When switching from another heartworm (0.9%) refused it. preventative product to SENTINEL SPECTRUM Chews, the first dose of How Supplied: SENTINEL SPECTRUM Chews are available in four SENTINEL SPECTRUM Chews should be given within a month of the last Animal Safety: In a margin of safety study, 40 ten-week-old puppies strengths, formulated according to the weight of the dog. Each strength is dose of the former product. (10 per group) were administered either a sham dose (0X) or doses of 1, available in color-coded packages of six or twelve chewable tablets each. 3, or 5X the maximum exposure dose of SENTINEL SPECTRUM Chews Flea Treatment and Prevention: Treatment with SENTINEL SPECTRUM once every two weeks for a total of seven treatments. Transient ataxia, Manufactured by: Virbac AH, Inc. Chews may begin at any time of the year, preferably starting one month lethargy, tremors, and salivation were seen in the 3X and 5X groups P.O. Box 162059 before fleas become active and continuing monthly through the end following each of the seven doses. Lethargy and ataxia were occasionally Fort Worth, TX 76161 of flea season. In areas where fleas are common year-round, monthly reported in sham-dosed (0X) and 1X dogs. Tremors were observed twice NADA 141-333, Approved by FDA. treatment with SENTINEL SPECTRUM Chews should continue the entire post-treatment in the 1X treatment group. Vomiting was seen in all year without interruption. treatment groups but at a higher incidence in the 3X and 5X groups. At © 2018 Virbac Corporation. All Rights Reserved. the 5X dose, shallow breathing was noted in two dogs and one dog was SENTINEL and SPECTRUM are registered trademarks of Virbac Corporation. To minimize the likelihood of flea reinfestation, it is important to treat all unable to stand following two different doses. All clinical signs resolved animals within a household with an approved flea protection product, within 24 hours. 2/18 as necessary. 302219 - 03 In field studies with ivermectin/pyrantel pamoate tablets, vomiting or diarrhea within 24 hours of dosing was rarely observed (1.1% of administered doses). The following adverse reactions have been reported in dogs following the use of ivermectin products: depression/lethargy, vomiting, anorexia, diarrhea, mydriasis, ataxia, staggering, convulsions, and hypersalivation. To report suspected adverse events, for technical assistance, or to obtain a copy of the Safety Data Sheet (SDS), contact Virbac AH, Inc. at 1-800-338-3659 or us.virbac.com. For additional For oral use in dogs only. information about adverse drug experience reporting for animal drugs, contact the FDA at 1-888-FDA-VETS or online at http:// www.fda.gov/AnimalVeterinary/SafetyHealth. Caution: Federal (U.S.A.) law restricts this drug to use by or on the order of a licensed veterinarian. Effectiveness: Prevention of the tissue larval stage of heartworm (Dirofilaria immitis) and the

® elimination of the adult stage of hookworm (Ancylostoma caninum, Uncinaria stenocephala, Description: IVERHART MAX Soft Chew is a combination of three anthelmintics (ivermectin/ Anyclostoma braziliense), roundworm (Toxocara canis, Toxascaris leonina), and tapeworm pyrantel pamoate/praziquantel). The soft chews are available in four sizes in color-coded (Dipylidium caninum, Taenia pisiformis) infections in dogs was demonstrated in well-controlled packages for oral administration to dogs according to their weight (see Dosage and laboratory studies. Administration). Palatability: In a field study of 132 dogs, IVERHART MAX Soft Chew was offered once monthly Indications: For use in dogs to prevent canine heartworm disease by eliminating the tissue for 3 months. The dogs voluntarily consumed 86.3% of the doses from the owner’s hand stage of heartworm larvae (Dirofilaria immitis) for a month (30 days) after infection and for or from a bowl within 5 minutes, 13.0% accepted the dose when it was offered in food or the treatment and control of roundworms (Toxocara canis, Toxascaris leonina), hookworms administered by placing onto the back of the dog’s tongue (pilling), and 0.7% of the doses were (Ancylostoma caninum, Uncinaria stenocephala, Ancylostoma braziliense), and tapeworms unable to be administered. (Dipylidium caninum, Taenia pisiformis). Animal Safety: Studies with ivermectin indicate that certain dogs of the Collie breed are more Dosage and Administration: IVERHART MAX Soft Chew should be administered orally at sensitive to the effects of ivermectin administered at elevated dose levels (more than 16 times monthly intervals and the recommended minimum dose level of 6 mcg of ivermectin per the target dose level of 6 mcg/kg) than dogs of other breeds. At elevated doses, sensitive kilogram (2.72 mcg/ lb), 5 mg of pyrantel (as pamoate salt) per kg (2.27 mg/lb), and 5 mg of dogs showed more adverse reactions, which included mydriasis, depression, ataxia, tremors, praziquantel per kg (2.27 mg/lb) of body weight, as follows: drooling, paresis, recumbency, excitability, stupor, coma, and death. No signs of toxicity were seen at 10 times the recommended dose (27.2 mcg/lb) in sensitive Collies. Data from these Pyrantel studies support the safety of ivermectin products in dogs, including Collies, when used at the Dog Weight Soft Chew Soft Chew Ivermectin Pamoate Praziquantel label recommended dose. Pounds per Month Size Content Content Content Because ivermectin and praziquantel are approximately 30% more bioavailable in the 6.0 to 12 1 Toy 34 mcg 28.5 mg 28.5 mg lVERHART MAX Soft Chew than in the ivermectin/pyrantel pamoate/praziquantel tablets used 12.1 to 25 1 Small 68 mcg 57 mg 57 mg in the following target animal safety studies, the margin of safety is narrower than reported in these studies. The potential for adverse reactions may be greater in individual dogs 25.1 to 50 1 Medium 136 mcg 114 mg 114 mg administered IVERHART MAX Soft Chew than ivermectin/ pyrantel pamoate/praziquantel tablets. 50.1 to 100 1 Large 272 mcg 228 mg 228 mg In a target animal safety study using ivermectin/pyrantel pamoate/praziquantel tablets, doses were administered to 8-week-old Beagle puppies at one, three, and five times the maximum IVERHART MAX Soft Chew is recommended for dogs 8 weeks of age or older. For dogs over 100 recommended dose of 12.5 mcg/kg ivermectin, 10.47 mg/kg pyrantel, and 10.47 mg/kg lbs, use the appropriate combination of these soft chews. praziquantel. The dogs were treated every 30 days for 6 months. Vomiting within 6 hours of dosing and soft or watery feces within 24 hours of dosing were observed. Other observations Remove only one dose at a time from the packaging. Return the remaining soft chew(s) to their during the study were: ano-genital swelling, lethargy, head movements, shallow, audible or box to protect from light. The soft chew can be offered to the dog by hand or added, intact, to a difficult breathing, and salivation. One dog in the 5X group had tremors and decreased activity. small amount of dog food. Care should be taken to ensure that the dog consumes the complete All of these signs were transient. No treatment was required. Histopathology showed testicular dose. The treated dog should be observed for a few minutes after administration to confirm that hypoplasia in the 3X and 5X groups (see Warnings). none of the dose has been lost or rejected. If it is suspected that any of the dose has been lost, redosing is recommended. In a laboratory safety study using ivermectin/pyrantel pamoate/praziquantel tablets, 12-week-old Beagle puppies receiving 3 and 5 times the recommended dose once weekly IVERHART MAX Soft Chew should be given at monthly intervals during the period of the year for 13 weeks demonstrated a dose-related decrease in testicular maturation compared to when mosquitoes (vectors), potentially carrying infective heartworm larvae, are active. The initial controls. In this study, all treated puppies had significantly higher cholesterol levels compared dose must be given within a month (30 days) after the dog’s first exposure to mosquitoes. The to untreated controls. final dose must be given within a month (30 days) after the dog’s last exposure to mosquitoes. In a reproductive safety study, adult males were treated at 37.5 mcg/kg ivermectin, 31.4 mg/ kg When replacing another heartworm preventative product in a heartworm disease prevention pyrantel, and 31.4 mg/kg praziquantel every 14 days during two full spermatogenic cycles program, the first dose of IVERHART MAX Soft Chew must be given within a month (30 days) of (112 days). The quality of semen and reproductive health were not affected by treatment. the last dose of the former medication. A heartworm test should be performed prior to switching Treatment-related vomiting and soft feces were reported during this study. heartworm preventative products. In a study of the effectiveness of ivermectin/pyrantel pamoate/praziquantel tablets for the If the interval between doses exceeds a month (30 days), the effectiveness of ivermectin can treatment of Toxocara canis, one 8.1 lb, 72-day-old puppy died 6 days after administration be reduced. Therefore, for optimal performance, the soft chew must be given once a month on of the label dose. This puppy and many other puppies in the study had high worm burdens or about the same day of the month. If treatment is delayed, whether by a few days or many, and were reported to have diarrhea, sometimes bloody, frequently before and after treatment. immediate treatment with IVERHART MAX Soft Chew and the recommended dosing regimen Dehydration and signs of anemia (pale mucous membranes) were the only abnormal gross will minimize the opportunity for the development of adult heartworms. necropsy finding observed. No definitive cause was determined. In a 90-day field study using Warnings: ivermectin/pyrantel pamoate/praziquantel tablets, the most serious adverse reactions (lethargy, For use in dogs only. Keep this and all drugs out of reach of children and pets. In safety limpness, and salivation) were seen in dogs weighing less than 10 lbs (see Precautions). studies with ivermectin/pyrantel pamoate/praziquantel tablets, testicular hypoplasia was Storage Information: Store at 20°C to 25°C (68°F to 77°F), excursions permitted between 15°C observed in some dogs receiving 3 and 5 times the maximum recommended dose monthly and 30°C (59°F to 86°F). for 6 months (see Animal Safety). How Supplied: IVERHART MAX Soft Chew is available in four dosage strengths (see Dosage In case of ingestion by humans, clients should be advised to contact a physician immediately. and Administration) for dogs of different weights. Each strength comes in a package of Physicians may contact a Poison Control Center for advice concerning cases of ingestion 6 soft chews. by humans.

Precautions: Use with caution in sick, debilitated, or underweight animals and dogs weighing NADA 141-441, Approved by FDA. less than 10 lbs (see Animal Safety). The safe use of this drug has not been evaluated in pregnant or lactating bitches. Manufactured by: All dogs should be tested for existing heartworm infection before starting treatment with IVERHART MAX Soft Chew, which is not effective against adult Dirofilaria immitis. Infected Virbac AH, Inc. dogs should be treated to remove adult heartworms and microfilariae before initiating a Fort Worth, TX 76137 USA heartworm prevention program. Phone: 1-800-338-3659 While some microfilariae may be killed by the ivermectin in IVERHART MAX Soft Chew at the © 2017 Virbac Corporation. recommended dose level, IVERHART MAX Soft Chew is not effective for microfilariae clearance. IVERHART MAX is a registered trademark of Virbac Corporation. A mild hypersensitivity-type reaction, presumably due to dead or dying microfilariae and 302143-03 particularly involving a transient diarrhea, has been observed in clinical trials with ivermectin alone after treatment of some dogs that have circulating microfilariae. 9/17 Adverse Reactions: In a field study with IVERHART MAX Soft Chew, self-limiting adverse reactions, including vomiting, diarrhea, lethargy, difficulty swallowing, excessive salivation, increased water consumption, and coughing were reported. Self-limiting adverse reactions, including lethargy, limpness, salivation, shaking, diarrhea, decreased appetite, licking lips, and belching were reported between 20 minutes and 72 hours following treatment in a field study with ivermectin/pyrantel pamoate/praziquantel tablets. DEPARTMENT h ATEGORYC h PEER REVIEWED

PANCREATICTOP 5 TOP 5 CYTOLOGIC FINDINGSBIOPSY IN ASPIRATES OF

ENLARGEDRon Ofri, DVM, PhD, DECVO LYMPH NODES Hebrew University of Jerusalem Rehovot, Israel Lisa M. Pohlman, DVM, MS, DACVP Kansas State University

22 cliniciansbrief.com January 2016 ymphntemortem node enlargement diagnosis of ispancreatic a common disease physical is a examinationchallenge. Histopathol- finding. LogyAFine-needle remains aspirationthe gold standard with of diagnosiscytology is for a fast, pancr noninvasive,eatic neopla- siaand and relatively pancreatitis. inexpensive Pancreatic biopsymeans providesof classifying a definitive the cause diag- nosisof enlargement. of pancreatitis, assuming a representative sample is obtained. An open or laparo- scopic approach can be made to collect samples.

September 2015 cliniciansbrief.com 23 TOP 5 h DIAGNOSTICS h PEER REVIEWED

To cytologically identify the cause of abnormal or TOP 5 CYTOLOGIC FINDINGS IN enlarged lymph nodes, clinicians must understand ASPIRATES OF ENLARGED LYMPH NODES the cell populations that comprise normal lymph nodes (Figure 1); however, it is relatively rare to 1. Reactive or Hyperplastic Node view a normal node on cytology, as normal nodes 2. Lymphoma are often difficult to palpate, making aspiration difficult. Cytologically, approximately 85% to 3. Lymphadenitis 90% of a normal lymph node is composed of small 4. Metastatic Disease lymphocytes,1,2 which are approximately 1 to 1.5 5. Accidental Salivary Gland Aspirate times the size of an RBC. Small lymphocytes have rounded nuclei with dense, dark-staining chromatin and have scant blue cytoplasm. The remaining 10% to 15% of cells in a normal lymph node include mostly medium (ie, nucleus 2-2.5× the diameter of an RBC) and large (ie, nucleus ≥3× the size of an RBC) lymphocytes, both of which have a fine, lightly staining chromatin pattern. Occasional plasma cells and macrophages and rare mast cells, neutrophils, and eosinophils may also be seen in a normal lymph node.2 Varying numbers of cytoplasmic fragments (ie, lympho- glandular bodies) that originate from ruptured lymphocytes are also a typical finding in both d FIGURE 1 Normal lymph node. The predominance of small normal and abnormal lymph node cytology.1 Mor- black arrows lymphocytes ( ) can be observed. A large phologic descriptions are based on staining with lymphocyte (red arrow), nuclear remnants (orange arrows), and cytoplasmic fragments from ruptured cells (blue arrows) Romanowsky-type stains (eg, Wright’s, Diff-Quik). are among a background of crenated and poorly preserved RBCs. Modified Wright’s stain; 600× magnification Following are 5 cytodiagnostic groups that should be considered in the evaluation of an aspirate of an enlarged node, according to the author.

Reactive or Hyperplastic Node Reactive lymphoid hyperplasia occurs when antigens in high concentrations reach the 1 draining lymph node and stimulate the immune system.2 As in a normal node, small lymphocytes still predominate cytologically, but an increase—typically constituting 15% to 25% of the cell population—in medium and large lymphocytes, plasma cells, ± both Mott cells (ie, plasma cells that contain packets of immunoglobulin [ie, d FIGURE 2 Reactive lymphoid hyperplasia. The characteristic heterogeneous population of cells comprising predominantly Russell bodies]) and scattered mast cells can be small lymphocytes (black arrows) with dense, dark chromatin expected (Figure 2). Macrophages may be mildly and scant cytoplasm, as well as plasma cells (blue arrows) increased. Neutrophils and eosinophils are rare. and scattered medium (red arrows) and large lymphocytes (yellow arrow), can be observed. Modified Wright’s stain; Morphologically normal mitotic figures may occa- 600× magnification sionally be seen.1

24 cliniciansbrief.com May 2019 An enlarged lymph node may sometimes have cytologic features more consistent with a normal node without the reactive components (eg, increased concentration of medium and large lymphocytes and plasma cells). In such cases, it is important to recognize that the node is enlarged and interpret the cytologic findings together with the node’s size. The interpretation may simply be lymphoid hyperplasia, but, in the author’s experience, there has been no clearly defined agreement among clinical pathologists on terminology (ie, lymphoid hyperplasia vs reactive lymphoid hyperplasia). Differentiation in terminology, however, is of little utility, as both cause lymph node enlarge- d FIGURE 3 Reactive lymphoid hyperplasia. The characteristic heterogeneous low-power view comprising predominantly ment due to local or systemic antigenic stimula- small lymphocytes (black arrow), with fewer medium tion and/or response (eg, inflammation, infection, lymphocytes (blue arrow), large lymphocytes (green arrow), neoplasia, immune-mediated disease).1,2 and scattered mast cells (red arrows), is present. A neutrophil for size comparison is indicated by the yellow arrow. The importance of viewing the sample at this power is not to In reactive or hyperplastic nodes, the overall definitively identify individual cells, which are confirmed on impression from a low-power view of a cytologic higher powers, but to obtain the overall impression of the present cell population. Modified Wright’s stain; 200× sample should be a heterogeneous population of magnification predominantly lymphoid cells, most of which are small (Figure 3).

Lymphoma Cytology is often sufficient for confirming a diagnosis of lymphoma. A homogeneous, 2 monomorphic population of medium and/ or large lymphocytes is the most common key cytologic feature of most lymphomas in dogs and cats (Figure 4).1,2 A diagnosis of lymphoma can be made when the medium and/or large lymphocytes comprise the vast majority of the cell population in an array of well-made, highly cellular cytologic smears that represent sampling from an entire d FIGURE 4 Lymphoma. A relatively homogeneous, monomor- lymph node or multiple nodes.1,2 Although lym- phic population of medium lymphocytes (arrows) is present. phoma is often a relatively straightforward diag- An RBC and neutrophils are boxed and circled, respectively, for nosis on cytology, prognostic information should size comparison. Modified Wright’s stain; 600× magnification be obtained after cytology through immuno- phenotyping and/or histopathology for specific classification of the disease process. In addition, some types of lymphoma (eg, small-cell variant, Cytology is often T-cell–rich, large B-cell) are more difficult to diagnose via cytology, so histopathology or PCR for sufficient for confirming a antigen receptor rearrangement may be required diagnosis of lymphoma. to confirm diagnosis.

May 2019 cliniciansbrief.com 25 TOP 5 h DIAGNOSTICS h PEER REVIEWED

Lymphadenitis mediated disease, neoplasia, and/or bacterial or Lymphadenitis is characterized by an fungal infection; fungal infection is also typically 2 accumulation of inflammatory cells in the associated with the presence of macrophages. 3 lymph node and is classified as either neutrophilic, eosinophilic, or histiocytic, depending Eosinophilic lymphadenitis is present if, in the on the type of cell(s) present. absence of blood contamination, >3% of nucleated cells are eosinophils.2 Eosinophilic lymphadenitis Neutrophilic lymphadenitis is present if neutro- is most commonly associated with hypersensitiv- phils comprise an estimated >5% of cells in the ity and/or parasitic infection (eg, flea bite allergy; absence of blood contamination.2 Neutrophilic Figure 5) but may also be seen with other condi- lymphadenitis may be associated with immune- tions, such as some neoplasms (eg, mast cell tumor, lymphoma, carcinoma), hypereosinophilic syndrome, or GI eosinophilic sclerosing fibroplasia.

Histiocytic lymphadenitis is present if there is a moderate increase in macrophages in the node and/or if multinucleated giant cells and/or epithelioid macrophages are among the histiocytic population. Conditions associated with histiocytic lymphadenitis include fungal infection, mycobac- teriosis, salmon poisoning disease, protothecosis, pythiosis, and hemosiderosis, among others.2

Multiple inflammatory cell types may be present in some cases (eg, neutrophilic and eosinophilic d FIGURE 5 Eosinophilic lymphadenitis in a dog with heartworm disease. A few of the many eosinophils are indicated by the lymphadenitis [Figure 6], neutrophilic and histio- arrows. Modified Wright’s stain; 600× magnification cytic [ie, pyogranulomatous] lymphadenitis).

Metastatic Disease A marked increase in cells expected in a lymph node (eg, mast cells) or the 4 presence of cells not expected in a lymph node (eg, epithelial cells) may be indicative of metastatic disease,1 particularly if features of malignancy are present in the cell population in question.

Carcinomas frequently metastasize to lymph nodes (Figure 7). Malignant epithelial cells often appear in large sheets or individually in a node. Epithelial cells should not be present in a lymph d FIGURE 6 Neutrophilic and eosinophilic lymphadenitis in a dog node and should raise suspicion for metastatic with stomatitis. Admixed with the resident lymphoid population disease when observed in a correctly collected of small lymphocytes (black arrows), medium lymphocytes sample.1,2 Tonsils, however, are an exception to (blue arrows), and plasma cells (circled) are increased numbers of nondegenerate neutrophils (red arrows) and eosinophils this, as squamous epithelial cells are occasionally (yellow arrows). Modified Wright’s stain; 600× magnification observed in aspirates.3

26 cliniciansbrief.com May 2019 Malignant melanomas commonly metastasize to lymph nodes; however, a diagnosis of metastatic melanoma must be based on the presence of neoplastic melanocytes—not the presence of pigment (eg, carbon, bile, hemosiderin, melanin), melano- phages, or siderophages in the node.1 Mast cell tumors also commonly metastasize to lymph nodes; however, caution must be exercised when assessing the significance of mast cells in lymph nodes, as mast cells are occasionally seen in a normal node and are often increased in number in reactive nodes.1,2 The presence of large groups or sheets of mast cells or of poorly differentiated mast cells in a lymph node is more indicative of d FIGURE 7 Metastatic carcinoma observed from fine-needle aspiration of the left submandibular lymph node. A cluster of metastatic disease as compared with the presence large, cohesive cells (black arrows) exhibiting anisocytosis, of increased numbers of morphologically normal anisokaryosis, and anisonucleosis can be observed; these cells mast cells.1 do not belong in a lymph node. Numerous intact lymphocytes, including small lymphocytes (orange arrow), medium lymphocytes (blue arrow), rare large lymphocytes (arrowhead), scat- Accidental Salivary Gland Aspirate tered neutrophils, and macrophages, can also be observed. The submandibular lymph node and sali- Nuclear remnants (pink arrows) of ruptured cells are also present and should not be confused with intact cells. Modified vary gland are in close proximity 2; thus, Wright’s stain; 600× magnification 5 it is common for clinical pathologists to receive salivary gland cytology submitted as a lymph node aspirate 2 or to occasionally identify epithelial cells from the salivary gland in a lymph node aspirate (Figure 8).1 It is crucial that clinicians are able to differentiate these cells and do not confuse them with malignancy.1 Normal salivary gland cytology contains individualized, cohesive clusters of secretory epithelial cells that have small, round, dark purple nuclei and foamy cytoplasm. Eosinophilic mucus is often present and can result in a windrowing effect (ie, lining up of cells) secondary to the viscous nature of the sample.1,2 n d FIGURE 8 Cohesive clusters of vacuolated, secretory epithelial cells (white arrows) from a salivary gland, with RBCs (blue arrow) and nuclear remnants of ruptured cells (black arrow). Modified Wright’s stain; 400× magnification

References 1. Messick JB. The lymph nodes. In: Valenciano AC, Cowell RL, eds. Canine and Feline Cytology. 3rd ed. St. Louis, MO: Elsevier; 2016:91-137. Cowell and Tyler’s Diagnostic Cytology and Hematology of the Dog 3. Bernreuter DC. Oropharynx and tonsils. In: Valenciano AC, Cowell and Cat. 4th ed. St. Louis, MO: Elsevier Mosby; 2014:180-194. RL, eds. Cowell and Tyler’s Diagnostic Cytology and Hematology of the 2. Raskin RE. Hemolymphatic system. In: Raskin RE, Meyer DJ, eds. Dog and Cat. 4th ed. St. Louis, MO: Elsevier Mosby; 2014:139.

May 2019 cliniciansbrief.com 27 Urinary St/ ™ ects Ox Sel ry vo Sa R U

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Trim: 8.125”W x 10.875”D CheckMark Communications Bleed: 8.375”W x 11.125”D Clinicians Brief Live Area: 7.125”W x 9.875”D February 2019 Ad code: NPPVDVD17F Ad size: 8.125”W x 10.875”D + bleed CASE IN POINT h NUTRITION/CARDIOLOGY h PEER REVIEWED

Respiratory Distress & Inappetence in a Border Collie

Kursten Pierce, DVM, DACVIM (Cardiology) Colorado State University Veterinary Teaching Hospital

Nora, a 3-year old, 41.1-lb (18.7-kg) spayed Nora had been fed 3 cups of a grain-free dry kibble diet border collie crossbreed, was presented on per day since adoption from a shelter 2.5 years previ- ously. The diet’s main ingredients included kangaroo, an emergency basis for respiratory distress kangaroo meal, chickpeas, peas, and lentils. Additional and inappetence of 48 hours’ duration. dietary history included occasional freeze-dried liver The owner reported a cough that had treats (maximum, 2-3 per week) from a local pet store and no human food. She was not receiving any vitamins, developed and progressively worsened, supplements, or medications other than her monthly as well as a decrease in appetite and parasite preventive. Nora was considered an otherwise activity, over the previous month. In the healthy dog, had no travel history since adoption, and was up-to-date on flea, tick, and heartworm preventives. 48 hours prior to presentation, Nora had also become reluctant to go on her Physical Examination regular daily walks. The owner additionally On presentation, Nora was quiet but alert and responsive and had a BCS of 3/9 and mild muscle wasting. She reported loss of muscle mass and noted was moderately dyspneic and tachypneic, with a resting that, in the few days before presentation, respiratory rate of 60 breaths per minute. She had weak Nora had seemed uncomfortable with femoral pulses (200 bpm), was normothermic (100.3°F an abdominal breathing component [37.9°C]), and had light pink mucous membranes, with a capillary refill time of 2 seconds. Jugular venous dis- and that respiratory rate and effort had tension was observed. Cardiac auscultation revealed progressively increased. tachycardia with a regular rhythm and a grade II/VI left apical systolic heart murmur. Harsh bronchovesicu- lar sounds and crackles were auscultated. Because of

May 2019 cliniciansbrief.com 29 CASE IN POINT h NUTRITION/CARDIOLOGY h PEER REVIEWED

concern for congestive heart failure (CHF), furosemide (2 mg/kg IV) was administered, the patient was placed in an oxygen cage, and a cardiac consultation was conducted.

Diagnosis Initial CBC and serum chemistry results were normal, with the exception of hyperlactatemia (blood lactate, 3.8 mmol/L; reference range, 0.20-1.44 mmol/L). Blood lactate concentration is a measure of anaerobic metabolism. Hyperlactatemia can occur secondary to decreased oxygen delivery (eg, volume depletion, blood loss, cardiogenic or septic shock), increased oxygen demand (eg, seizures, exercise), inadequate oxygen utilization (eg, systemic inflammatory response syndrome, sepsis), and/or drugs or toxins.1 Hyperlactatemia in this patient was suspected to be due to hypoperfusion secondary to active CHF and systolic dysfunction. d FIGURE 1 2D echocardiographic image of the left ventricle from the right parasternal short axis view. There is decreased thickness of the LV walls and severe dilation of the LV cavity Nora was hypotensive and had a systolic blood pres- consistent with DCM. sure of 85 mm Hg obtained via Doppler from the left dorsal metatarsal with the patient in right lateral recumbency. ECG revealed sinus tachycardia with a heart rate ranging from 186 to 210 bpm. No ectopic beats were visualized on 6-lead ECG or telemetry.

An echocardiogram and thoracic radiographs were obtained. The echocardiogram revealed decreased left ventricular (LV) wall thickness, severe dilation of the LV chamber (ie, eccentric hypertrophy), and severely reduced LV systolic function. Severe left atrial enlargement with a moderate degree of cen- trally directed left atrioventricular valve regurgitation (suspected functional) was observed. The left atrioventricular valve leaflets appeared normal in thickness with poor coaptation due to annular stretch. In addition, there was mild dilation of the right atrium and ventricle with a mild degree of right atrioventricular valve regurgitation. Results d M-mode echocardiographic image from the right FIGURE 2 of echocardiography were consistent with dilated parasternal short axis view at the level of the mitral valve 2,3 leaflets showing severely increased E-point-to-septal cardiomyopathy (DCM; Figures 1-4). separation consistent with DCM Thoracic radiographs Figures( 5 and 6, page 32) revealed marked cardiomegaly with a globoid cardiac silhouette and severe left atrial enlargement.

30 cliniciansbrief.com May 2019 Pulmonary venous congestion and an interstitial pulmonary pattern in the perihilar and caudal lung fields were consistent with cardiogenic pulmonary edema.

Because of the patient’s dietary history of being fed a grain-free diet for the last 2.5 years and concern for diet-associated DCM, whole blood and plasma taurine levels were evaluated and found to be normal (plasma taurine, 112 nmol/mL; reference range, 60-120 nmol/mL: whole blood taurine, 262 nmol/ mL; reference range, 200-350 nmol/mL).4 Cardio- myopathy secondary to taurine deficiency has been reported in golden retrievers5-7 and cocker spaniels, d FIGURE 3 2D echocardiographic image from the right paraster- which are taurine- and L-carnitine–responsive nal long axis view. The left atrium and left ventricle are severely breeds.7,8 Grain-free diets have been linked to DCM dilated. The mitral valve leaflets are normal in thickness and in patients with normal taurine levels, suggesting an have no evidence of degenerative mitral valve disease. alternative mechanism in the development of DCM. Potential mechanisms are under investigation. DCM may be suspected based on dietary history, breed (ie, atypical breed for DCM, lack of familial history, breed predisposition), and the elimination of other underlying causes (ie, myocarditis, toxicity, tachycardia-mediated cardiomyopathy).

DIAGNOSIS: DIET-ASSOCIATED DILATED CARDIOMYOPATHY Treatment & Long-Term Management Cardiac medications for management of CHF and systolic dysfunction, including furosemide (2.14 mg/kg PO q12h), pimobendan (0.27 mg/kg PO q12h), and enalapril (0.53 mg/kg PO q12h), were initiated. Taurine (26.7 mg/kg PO q12h) was added as a supplement due to concern for diet-associated DCM. Because the exact mechanism of diet-associated DCM is not well understood and taurine has d FIGURE 4 2D echocardiographic image with color Doppler from the left parasternal apical view. There is severe dilation been shown to be beneficial for cardiovascular of the left atrium, left ventricle, and mitral valve annulus disease (ie, antioxidant effects, protection against resulting in a central jet of mitral regurgitation. Mitral valve ischemia-reperfusion injury, modulation of intra- leaflets are normal in thickness, with no evidence of cellular calcium concentrations), taurine supple- degenerative mitral valve disease. mentation was continued in this patient. Nora was CHF = congestive heart failure transitioned to a commercial, nonboutique, non- DCM = dilated cardiomyopathy exotic protein, nongrain-free diet (see Treatment LV = left ventricular at a Glance, page 33).

May 2019 cliniciansbrief.com 31 CASE IN POINT h NUTRITION/CARDIOLOGY h PEER REVIEWED

Nora was presented for a recheck examination breaths per minute) and normotensive (systolic with thoracic radiography, renal values with blood pressure, 115 mm Hg). Coughing had electrolytes, and blood pressure 10 days after resolved, and serum chemistry results showed no starting cardiac medications. Results of the subse- evidence of azotemia or electrolyte derangements. quent testing revealed adequate control of CHF and radiographic resolution of pulmonary edema. Outcome Nora was eupneic (resting respiratory rate, 20 Nora was presented for a recurrence of CHF, dyspnea, and coughing a month after the recheck examination and responded to up-titration of diuretic therapy. At the 3-month recheck after initial presentation (ie, 2 months after presentation for recurrence), CHF and systolic dysfunction were stable.

Discussion DCM can be idiopathic, genetic, and/or primary. DCM can also occur secondary to infectious disease (eg, myocarditis, parvovirus in puppies, Chagas disease), toxicity (eg, doxorubicin-induced), or nutritional causes (eg, taurine or L-carnitine deficiency, diet-associated) or can be tachycardia-induced/ mediated (eg, myocardial failure due to persistent tachyarrhythmias).3,9 Inherited DCM has been reported in large- and giant-breed dogs (eg, Dober- man pinschers, Great Danes, Irish wolfhounds).2,3,10

In July 2018, the US FDA released a notice regarding reports from veterinary cardiologists of suspected d FIGURE 5 Ventrodorsal thoracic radiograph obtained one day after starting cardiac medications for CHF secondary to diet-associated DCM in dogs not typically predis- suspected diet-associated DCM. There is severe cardiomegaly posed to DCM. Since then, the FDA has released an with resolving pulmonary edema. additional update on their investigation, reporting over 300 dogs with suspected diet-associated DCM as of November 2018.11 Diets of concern include pet foods containing peas, lentils, fava beans, tapioca, barley, chickpeas, other legume seeds, and potatoes as the main ingredient and/or exotic ingredients (eg, kangaroo, duck, buffalo, bison, venison).9,11 Pet food from boutique companies (ie, small manufacturers) that contain exotic ingredients (eg, nontraditional protein sources) and/or are grain-free are also suspected to be linked to diet-associated DCM.9,12-14 See Suggested Reading, page 34, for a resource providing additional information and updates on these diets and their association with d FIGURE 6 Left lateral thoracic radiograph obtained one day DCM.12,13 It is important to note that diets that meet after starting cardiac medications for CHF secondary to suspected diet-associated DCM. There is severe cardiomegaly minimum nutrient standards and that are formu- with resolving pulmonary edema. lated based on Association of American Feed Control

32 cliniciansbrief.com May 2019 Officials recommendations do not necessarily The subclinical occult phase of DCM can last up to ensure a balanced or regulated diet. There have been 2 to 4 years, whereas median survival time in dogs no documented cases of diet-associated DCM in with development of CHF secondary to primary dogs eating a commercial diet from an established DCM is reportedly 6 to 12 months.3,17,18 Follow-up major pet food company. Pet foods should ideally echocardiography should be recommended every 3 undergo feeding trials to verify complete and bal- to 6 months to monitor for improvement. Reverse anced nutrition.15 remodeling may be visualized in some patients in this timeframe, whereas others may take longer DCM has also reportedly been diagnosed in a few (ie, 6-9 months) or show no improvement.9,11,13 subsets of dogs, including primary DCM in predis- For example, a study has shown golden retrievers posed breeds (unrelated to diet), diet-associated with taurine deficiency and DCM to have slow and DCM in dogs with normal taurine levels, and steady improvement over a 6- to 12-month period diet-associated DCM in dogs with taurine defi- after diet was changed and taurine supplementa- ciency (eg, golden retrievers).5,9,11,13 A previous tion was initiated. Of the 11 dogs with CHF in this study demonstrated that dogs with DCM that were study, 9 had resolution of congestion, and 5 were fed a grain-free diet had a greater magnitude of tapered off diuretics completely.5 LV dilation on echocardiography as compared Continues h with dogs with DCM that were fed a nongrain-free diet.14 The exact mechanism for the development of DCM in dogs fed these diets is not completely TREATMENT AT A GLANCE understood and may be multifactorial.9,11-14,16 Theorized causes under investigation include h The patient should be transitioned to a commercial, reduced bioavailability of nutrients due to interac- nonboutique, nonexotic protein, nongrain-free diet tions with other ingredients, nutrient deficiencies, with standard ingredients manufactured by an established company.9,11-13,15 and potential for cardiotoxic ingredients.9 h Taurine should be supplemented if the patient has Recommendations for treatment and additional confirmed or suspected taurine deficiency.4,5,9,11,13 diagnostics vary by patient but may include obtain- h Based on echocardiography, medications such as 9,11-13,15 ing a detailed dietary history, evaluating pimobendan and ACE inhibitors may be prescribed 4 whole blood and plasma taurine levels, providing to support cardiac function, decrease preload, and taurine supplementation, screening for DCM via inhibit the renin-angiotensin-aldosterone system. echocardiography, initiating cardiac medications h If CHF is present on thoracic radiographs, therapy as indicated,5,9,11-13 and transitioning the patient to should be instituted with diuretics, pimobendan, and a nonboutique, nonexotic protein, nongrain-free ACE inhibitors or other cardiac medications as diet with standard ingredients and manufactured indicated based on echocardiography.3,17,18 by an established company (see Take-Home h Additional therapies (eg, antiarrhythmic drugs) may be Messages and Suggested Reading, next page).9,15 recommended if an arrhythmia has been documented. Additional diagnostics (eg, ECG, 24-hour Holter monitoring, thoracic radiography, N-terminal prohormone of brain natriuretic peptide, troponin levels) may be suggested based on cardiac evaluation. The specific diet of patients with suspected diet-associated DCM should be reported to the CHF = congestive heart failure FDA.9,11 Owners of dogs with diet-associated DCM DCM = dilated cardiomyopathy should be questioned if other pets in the house- LV = left ventricular hold are eating the same diet.

May 2019 cliniciansbrief.com 33 CASE IN POINT h NUTRITION/CARDIOLOGY h PEER REVIEWED

TAKE-HOME MESSAGES

h A detailed dietary history should be obtained in all patients suspected of having DCM. Diet changes should be recommended if the patient is being fed a diet of concern for diet-associated DCM.9,12-14

h Evaluating plasma and whole blood taurine levels, as well as initiating taurine supplementation, should be considered. Taurine should be supplemented until levels are normal and in cases in which the owner declines to submit taurine levels due to financial constraints.

h If a patient is being fed a diet of concern and is experiencing cardiac clinical signs (eg, dyspnea, tachypnea, coughing, exercise intolerance, syncope), a full cardiac diagnostic investigation, including echocardiography, is recommended to evaluate for possible diet-associated DCM.

h Any suspected or documented cases of diet-associated DCM should be reported to the FDA.11 n

References 1. Pang DS, Boysen S. Lactate in veterinary critical care: Medical Center at Tufts University Clinical Nutrition Service website. pathophysiology and management. J Am Anim Hosp Assoc. http://vetnutrition.tufts.edu/2018/06/a-broken-heart-risk-of-heart- 2007;43(5):270-279. disease-in-boutique-or-grain-free-diets-and-exotic-ingredients. 2. Wess G, Domenech O, Dukes-McEwan J, Häggström J, Gordon S. Published June 4, 2018. Accessed March 11, 2019. European Society of Veterinary Cardiology screening guidelines 13. Freeman LM. It’s not just grain-free: an update on diet-associated for dilated cardiomyopathy in Doberman pinschers. J Vet Cardiol. dilated cardiomyopathy. Cummings Veterinary Medical Center 2017;19(5):405-415. at Tufts University Clinical Nutrition Service website. http:// 3. Estrada AH, Maisenbacher HW III. Dilated cardiomyopathy in dogs. vetnutrition.tufts.edu/2018/11/dcm-update. Published November In: Bonagura JD, Twedt DC, eds. Kirk’s Current Veterinary Therapy XV. 29, 2018. Accessed March 11, 2019. St. Louis, MO: Elsevier Saunders; 2014:795-800. 14. Adin D. Echocardiographic phenotype of canine dilated 4. University of California Davis School of Veterinary Medicine. Josh cardiomyopathy differs based on diet. Paper presented at: Stern cardiac genetics laboratory. UC Davis website. https://ccah. American College of Veterinary Internal Medicine Forum; June 14-16, vetmed.ucdavis.edu/areas-study/genetics/josh-stern-cardiac- 2018; Seattle, Washington. https://eventscribe.com/2018/ACVIM/ genetics-laboratory. Accessed March 11, 2019. fsPopup.asp?Mode=PresInfo&PresentationID=393940. Accessed March 11, 2019. 5. Kaplan JL, Stern JA, Fascetti AJ, et al. Taurine deficiency and dilated cardiomyopathy in golden retrievers fed commercial diets. PLoS 15. World Small Animal Veterinary Association. WSAVA global nutrition One. 2018;13(12):e0209112. guidelines. WSAVA website. https://www.wsava.org/WSAVA/media/ Documents/Guidelines/WSAVA-Global-Nutritional-Assessment- 6. Bélanger MC, Ouellet M, Queney G, Moreau M. Taurine-deficient Guidelines-2011-final.pdf. Accessed March 11, 2019. dilated cardiomyopathy in a family of golden retrievers. J Am Anim Hosp Assoc. 2005;41(5):284-291. 16. Mansilla WD, Marinangeli CPF, Ekenstedt KJ, et al. Special topic: the association between pulse ingredients and canine 7. Kramer GA, Kittleson MD, Fox PR, Lewis J, Pion PD. Plasma taurine dilated cardiomyopathy: addressing the knowledge gaps before concentrations in normal dogs and in dogs with heart disease. J Vet establishing causation. J Anim Sci. 2019;97(3):983-997. Intern Med. 1995;9(4):253-258. 17. Tidholm A. Survival in dogs with dilated cardiomyopathy and 8. Kittleson MD, Keene B, Pion PD, Loyer CG. Results of the multicenter congestive heart failure treated with digoxin, furosemide spaniel trial (MUST): taurine- and carnitine-responsive dilated and propranolol: a retrospective study of 62 dogs. J Vet cardiomyopathy in American cocker spaniels with decreased Cardiol. 2006;8(1):41-47. plasma taurine concentration. J Vet Intern Med. 1997;11(4):204-211. 18. Borgarelli M, Santilli RA, Chiavegato D, et al. Prognostic 9. Freeman LM, Stern JA, Fries R, Adin DB, Rush JE. Diet-associated indicators for dogs with dilated cardiomyopathy. J Vet Intern Med. dilated cardiomyopathy in dogs: what do we know? J Am Vet Med 2006;20(1):104-110. Assoc. 2018;253(11):1390-1394. 10. Stern JA, Ueda Y. Inherited cardiomyopathies in veterinary medicine. Pflugers Arch - Eur J Physiol. 2018. https://doi. org/10.1007/s00424-018-2209-x. Accessed March 11, 2019. Suggested Reading Clinical Nutrition Service at Cummings Veterinary Medical Center at 11. U.S. Food & Drug Administration. FDA investigating potential Tufts University. http://vetnutrition.tufts.edu/petfoodology. connection between diet and cases of canine heart disease. https://www.fda.gov/animalveterinary/newsevents/cvmupdates/ World Small Animal Veterinary Association. WSAVA global nutrition ucm613305.htm. Published July 12, 2018. Accessed March 11, 2019. guidelines. WSAVA website. https://www.wsava.org/WSAVA/media/ Documents/Guidelines/WSAVA-Global-Nutritional-Assessment- 12. Freeman LM. A broken heart: risk of heart disease in boutique Guidelines-2011-final.pdf. or grain-free diets and exotic ingredients. Cummings Veterinary

DCM = dilated cardiomyopathy

34 cliniciansbrief.com May 2019 Prescribe

peace of mind.

Powerful protection can also be gentle:

✓ Safe for puppies as young as 8 weeks of age weighing 4 lbs or more

✓ Over 140 million doses of afoxolaner have been prescribed1

✓ And it’s the only ﬂ ea and tick control product indicated for the prevention of Borrelia burgdorferi infections as a direct result of killing Ixodes scapularis vector ticks

IMPORTANT SAFETY INFORMATION: N is for use in dogs only. The most freuently reported adverse

1 reactions include vomiting, pruritus, lethargy, diarrhea and lack of appetite. The safe use of N in pregnant, Data on fi le. breeding, or lactating dogs has not been evaluated. Use with caution in dogs with a history of seiures or neurologic disorders. For more information, see the full prescribing information or visit www.NeGardlinic.com. NeGard® is a registered trademark of the Boehringer Ingelheim Group. ©2019 Boehinger Ingelheim Animal Health USA Inc., Duluth, GA 3009. All rights reserved. PET-113-NE0119. See page 36 for product information summary.

xng311744_NG-SafetyAd-CB-8.125x10.875_rsg.indd 1 1/16/19 11:33 AM CAUTION: Federal (USA) law restricts this drug to use by or on the order of a licensed veterinarian. enrolled and completed the study. Another dog with a history of seizures had a seizure 19 days Description: after the third dose of NexGard. The dog remained enrolled and completed the study. A third dog NexGard® (afoxolaner) is available in four sizes of beef-flavored, soft chewables for oral with a history of seizures received NexGard and experienced no seizures throughout the study. administration to dogs and puppies according to their weight. Each chewable is formulated to Post-Approval Experience (July 2018): provide a minimum afoxolaner dosage of 1.14 mg/lb (2.5 mg/kg). Afoxolaner has the chemical The following adverse events are based on post-approval adverse drug experience reporting. Not composition 1-Naphthalenecarboxamide, 4-[5- [3-chloro-5-(trifluoromethyl)-phenyl]-4, 5-dihydro- all adverse events are reported to FDA/CVM. It is not always possible to reliably estimate the 5-(trifluoromethyl)-3-isoxazolyl]-N-[2-oxo-2-[(2,2,2-trifluoroethyl)amino]ethyl. adverse event frequency or establish a causal relationship to product exposure using these data. Indications: The following adverse events reported for dogs are listed in decreasing order of reporting NexGard kills adult fleas and is indicated for the treatment and prevention of flea infestations frequency for NexGard: (Ctenocephalides felis), and the treatment and control of Black-legged tick (Ixodes scapularis), Vomiting, pruritus, lethargy, diarrhea (with and without blood), anorexia, seizure, hyperactivity/ American Dog tick (Dermacentor variabilis), Lone Star tick (Amblyomma americanum), and Brown restlessness, panting, erythema, ataxia, dermatitis (including rash, papules), allergic reactions dog tick (Rhipicephalus sanguineus) infestations in dogs and puppies 8 weeks of age and older, (including hives, swelling), and tremors. weighing 4 pounds of body weight or greater, for one month. NexGard is indicated for the prevention of Borrelia burgdorferi infections as a direct result of killing Ixodes scapularis vector ticks. Contact Information: For a copy of the Safety Data Sheet (SDS) or to report suspected adverse drug events, contact Dosage and Administration: Merial at 1-888-637-4251 or www.nexgardfordogs.com. NexGard is given orally once a month, at the minimum dosage of 1.14 mg/lb (2.5 mg/kg). For additional information about adverse drug experience reporting for animal drugs, contact Dosing Schedule: FDA at 1-888-FDA-VETS or online at http://www.fda.gov/AnimalVeterinary/SafetyHealth. Body Afoxolaner Per Chewables Mode of Action: Weight Chewable (mg) Administered Afoxolaner is a member of the isoxazoline family, shown to bind at a binding site to inhibit insect 4.0 to 10.0 lbs. 11.3 One and acarine ligand-gated chloride channels, in particular those gated by the neurotransmitter gamma-aminobutyric acid (GABA), thereby blocking pre- and post-synaptic transfer of chloride 10.1 to 24.0 lbs. 28.3 One ions across cell membranes. Prolonged afoxolaner-induced hyperexcitation results in uncontrolled 24.1 to 60.0 lbs. 68 One activity of the central nervous system and death of insects and acarines. The selective toxicity 60.1 to 121.0 lbs. 136 One of afoxolaner between insects and acarines and mammals may be inferred by the differential Over 121.0 lbs. Administer the appropriate combination of chewables sensitivity of the insects and acarines’ GABA receptors versus mammalian GABA receptors. Effectiveness: NexGard can be administered with or without food. Care should be taken that the dog In a well-controlled laboratory study, NexGard began to kill fleas four hours after initial consumes the complete dose, and treated animals should be observed for a few minutes to administration and demonstrated >99% effectiveness at eight hours. In a separate well- ensure that part of the dose is not lost or refused. If it is suspected that any of the dose has controlled laboratory study, NexGard demonstrated 100% effectiveness against adult fleas 24 been lost or if vomiting occurs within two hours of administration, redose with another full dose. hours post-infestation for 35 days, and was ≥93% effective at 12 hours post-infestation through If a dose is missed, administer NexGard and resume a monthly dosing schedule. Day 21, and on Day 35. On Day 28, NexGard was 81.1% effective 12 hours post-infestation. Flea Treatment and Prevention: Dogs in both the treated and control groups that were infested with fleas on Day -1 generated Treatment with NexGard may begin at any time of the year. In areas where fleas are common year- flea eggs at 12- and 24-hours post-treatment (0-11 eggs and 1-17 eggs in the NexGard treated round, monthly treatment with NexGard should continue the entire year without interruption. 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 To minimize the likelihood of flea reinfestation, it is important to treat all animals within a unable to produce any eggs (0-1 eggs) while fleas from dogs in the control group continued to household with an approved flea control product. produce eggs (1-141 eggs). Tick Treatment and Control: In a 90-day US field study conducted in households with existing flea infestations of varying Treatment with NexGard may begin at any time of the year (see Effectiveness). severity, the effectiveness of NexGard against fleas on the Day 30, 60 and 90 visits compared Contraindications: with baseline was 98.0%, 99.7%, and 99.9%, respectively. There are no known contraindications for the use of NexGard. Collectively, the data from the three studies (two laboratory and one field) demonstrate that Warnings: NexGard kills fleas before they can lay eggs, thus preventing subsequent flea infestations after Not for use in humans. Keep this and all drugs out of the reach of children. In case of accidental the start of treatment of existing flea infestations. ingestion, contact a physician immediately. In well-controlled laboratory studies, NexGard demonstrated >97% effectiveness against Precautions: Dermacentor variabilis, >94% effectiveness against Ixodes scapularis, and >93% effectiveness Afoxolaner is a member of the isoxazoline class. This class has been associated with neurologic against Rhipicephalus sanguineus, 48 hours post-infestation for 30 days. At 72 hours post- adverse reactions including tremors, ataxia, and seizures. Seizures have been reported in dogs infestation, NexGard demonstrated >97% effectiveness against Amblyomma americanum for 30 receiving isoxazoline class drugs, even in dogs without a history of seizures. Use with caution days. In two separate, well-controlled laboratory studies, NexGard was effective at preventing in dogs with a history of seizures or neurologic disorders (see Adverse Reactions and Post- Borrelia burgdorferi infections after dogs were infested with Ixodes scapularis vector ticks 28 Approval Experience). days post-treatment. The safe use of NexGard in breeding, pregnant or lactating dogs has not been evaluated. Animal Safety: Adverse Reactions: In a margin of safety study, NexGard was administered orally to 8 to 9-week-old Beagle puppies In a well-controlled US field study, which included a total of 333 households and 615 treated at 1, 3, and 5 times the maximum exposure dose (6.3 mg/kg) for three treatments every 28 days, dogs (415 administered afoxolaner; 200 administered active control), no serious adverse followed by three treatments every 14 days, for a total of six treatments. Dogs in the control reactions were observed with NexGard. group were sham-dosed. There were no clinically-relevant effects related to treatment on physical examination, body weight, food consumption, clinical pathology (hematology, clinical Over the 90-day study period, all observations of potential adverse reactions were recorded. chemistries, or coagulation tests), gross pathology, histopathology or organ weights. Vomiting The most frequent reactions reported at an incidence of > 1% within any of the three months of occurred throughout the study, with a similar incidence in the treated and control groups, observations are presented in the following table. The most frequently reported adverse reaction including one dog in the 5x group that vomited four hours after treatment. 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 In a well-controlled field study, NexGard was used concomitantly with other medications, such anorexia during the study, and two of those dogs experienced anorexia with the first dose but as vaccines, anthelmintics, antibiotics (including topicals), steroids, NSAIDS, anesthetics, and not subsequent doses. antihistamines. No adverse reactions were observed from the concomitant use of NexGard with other medications. Table 1: Dogs With Adverse Reactions. Storage Information: Treatment Group Store at or below 30°C (86°F) with excursions permitted up to 40°C (104°F). Afoxolaner Oral active control How Supplied: NexGard is available in four sizes of beef-flavored soft chewables: 11.3, 28.3, 68 or N1 % (n=415) N2 % (n=200) 136 mg afoxolaner. Each chewable size is available in color-coded packages of 1, 3 or 6 Vomiting (with and without blood) 17 4.1 25 12.5 beef-flavored chewables.

Dry/Flaky Skin 13 3.1 2 1.0 NADA 141-406, Approved by FDA Diarrhea (with and without blood) 13 3.1 7 3.5 Marketed by: Frontline Vet Labs™, a Division of Merial, Inc. Lethargy 7 1.7 4 2.0 Duluth, GA 30096-4640 USA Anorexia 5 1.2 9 4.5 Made in Brazil. ®NexGard is a registered trademark, and 1Number of dogs in the afoxolaner treatment group with the identified abnormality. TMFRONTLINE VET LABS is a trademark, of Merial. 2Number of dogs in the control group with the identified abnormality. ©2018 Merial. All rights reserved. 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. 1050-4493-07 This dog experienced a third seizure one week after receiving the third dose. The dog remained Rev. 05/2018 FROM PAGE TO PATIENT

Designed to bridge the gap between research pages and daily practice protocol, the following pearls offer tips and techniques to grow the general practitioner’s clinical excellence.

Transmission of Methicillin- Size Is Not a Factor 38 Resistant Staphylococci in 48 in Standard of Care Small Animal Clinics Adolf K. Maas III, DVM, DABVP Jason W. Stull, VMD, MPVM, PhD, (Reptile & Amphibian), CertAqV DACVPM Aelurostrongylosis in Cats Survival to Discharge or 51 Donato Traversa, DVM, PhD, 42 Transfer in Stuporous or DipEVPC Comatose Dogs & Cats Mark Troxel, DVM, DACVIM RESEARCH NOTES (Neurology) Caudal Articular 52 Process Dysplasia Hemoabdomen in 44 Large vs Small Dogs Perfectionism & Its Elke Rudloff, DVM, DACVECC, cVMA 55 Impact on Performance & Mental Health Antacid Therapy in Cats Marie Holowaychuk, DVM, DACVECC 47 with Chronic Kidney Disease JD Foster, VMD, DACVIM

May 2019 cliniciansbrief.com 37 FROM PAGE TO PATIENT

Transmission of Methicillin- Resistant Staphylococci in Small Animal Clinics

Jason W. Stull, VMD, MPVM, PhD, DACVPM University of Prince Edward Island The Ohio State University

In the Literature Worthing KA, Brown J, Gerber L, Trott DJ, Abraham S, Norris JM. Methicillin-resistant staphylococci amongst veterinary personnel, personnel-owned pets, patients and the hospital environment of two small animal veterinary hospitals. Vet Microbiol. 2018;223:79-85.

FROM THE PAGE …

Staphylococci are frequently carried on the skin and mucosal surfaces of dogs, cats, and humans. Staphylococcus aureus in humans and S pseudintermedius in dogs are causes of opportunistic infections, and the emergence of methicillin resistance in these species (MRSA and MRSP, respectively) has resulted in infections that are resistant to numerous antimicrobial classes and challenging to treat. Movement of these pathogens among individuals of the same species, among those of different species (eg, dogs and humans), and in the hospital environment is not well understood.

This study investigated the prevalence of MRSA and MRSP in 2 veterinary companion animal hospitals (one general practice and one referral practice). Forty-six veterinary staff, 79 staff-owned dogs and cats, 151 clinically normal canine patients, and 25 environmental sites were sampled to identify the presence of MRSA and MRSP. Whole genome sequencing was used to investigate relatedness between isolates.

MRSA was isolated from veterinary staff (8%) but no animals. MRSP was isolated from dogs (staff-owned, 8%; patients, 7%) but no veterinary staff. Neither pathogen was isolated from hospital environmental surfaces. Based on relatedness of isolates, transmission was likely among dogs living in the same household but not among other groups of dogs or among dogs, humans, and the environment. The MRSP isolates were resistant to multiple antimicrobial classes in addition to β lactams, which emphasizes the challenge of treating these infections.

Although this study highlights the strong species propensity for MRSA (in humans) and MRSP (in dogs) in a non- outbreak setting, it is important to note that these infections are not always species-specific. Several studies have

Continues on page 40 h

38 cliniciansbrief.com May 2019 1750 Veterinarians can’t be wrong! That’s the number of Veterinarians that chose an iM3 CR7 forfor their pracpractictice. The number 1 choice worldwide for CR Veterinary Dental Imaging is as clear as the images from our CR7. •Highest resolution at 25 lp • Largest range of image plate sizes • Ideal for extremities & orthopedic surgery • iM3 unlimited technical support, German made

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® FROM PAGE TO PATIENT h CONTINUED FROM PAGE 38 VETORYL CAPSULES (trilostane) 5 mg, 10 mg, 30 mg, 60 mg and 120 mg strengths Adrenocortical suppressant for oral use in dogs only.

BRIEF SUMMARY (For Full Prescribing Information, see package insert.)

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

DESCRIPTION: VETORYL Capsules are an orally documented infections with MRSA in pets, MRSP in humans, and both organ- active synthetic steroid analogue that blocks production of hormones produced in the adrenal isms on veterinary staff clothing and in the veterinary hospital environment.1-3 cortex of dogs.

Veterinary hospital-associated (ie, nosocomial) outbreaks of MRSA and MRSP INDICATION: VETORYL Capsules are indicated for the treatment of pituitary- and adrenal-dependent in which humans, patients, and environmental contamination all likely contrib- hyperadrenocorticism in dogs. 4,5 uted to the outbreak have been identified. Guidelines exist to assist practi- CONTRAINDICATIONS: The use of VETORYL tioners in MRSA and MRSP infection risks, diagnosis, therapy, and prevention Capsules is contraindicated in dogs that have demonstrated hypersensitivity to trilostane. Do not (see Suggested Reading). use VETORYL Capsules in animals with primary hepatic disease or renal insufficiency. Do not use in pregnant dogs. Studies conducted with trilostane in laboratory animals have shown teratogenic effects and early pregnancy loss.

… TO YOUR PATIENTS WARNINGS: In case of overdosage, symptomatic treatment of hypoadrenocorticism with Key pearls to put into practice: corticosteroids, mineralocorticoids and intravenous fluids may be required. Angiotensin converting enzyme (ACE) inhibitors should be used with caution All veterinary staff should understand the health risks MRSA and MRSP with VETORYL Capsules, as both drugs have aldosterone-lowering effects which may be additive, pose to their own pets, their patients, pet owners, and themselves, includ- impairing the patient’s ability to maintain normal electrolytes, blood volume and renal perfusion. 1ing the potential for transmission among humans, pets, and the hospital Potassium sparing diuretics (e.g. spironolactone) environment. Healthy animals and humans can carry these pathogens, should not be used with VETORYL Capsules as both drugs have the potential to inhibit aldosterone, contaminate surfaces, and transmit them to others. increasing the likelihood of hyperkalemia.

HUMAN WARNINGS: Keep out of reach of children. Culture and susceptibility testing are warranted for infections that are Not for human use. Wash hands after use. Do not refractory to empiric therapy or that are otherwise more likely to be empty capsule contents and do not attempt to divide the capsules. Do not handle the capsules if pregnant 2multidrug-resistant. Recent antimicrobial use, ownership by healthcare or if trying to conceive. Trilostane is associated with teratogenic effects and early pregnancy loss in workers, and extended hospitalization time are risk factors for laboratory animals. In the event of accidental methicillin-resistant staphylococci colonization or infection in pets.4,6 ingestion/overdose, seek medical advice immediately and take the labeled container with you.

Infection control practices—including use of personal protective PRECAUTIONS: Hypoadrenocorticism can develop at any dose of VETORYL Capsules. A small equipment (eg, disposable gloves, gowns) when indicated, routine percentage of dogs may develop corticosteroid 3environmental cleaning and disinfection, and routine hand-washing or withdrawal syndrome within 10 days of starting treatment. Mitotane (o,p’-DDD) treatment will reduce use of alcohol-based hand sanitizer—are key to MRSA and MRSP control adrenal function. Experience in foreign markets suggests that when mitotane therapy is stopped, an and prevention. Such practices should be communicated clearly to and interval of at least one month should elapse before consistently practiced by all staff. the introduction of VETORYL Capsules. The use of VETORYL Capsules will not affect the adrenal tumor itself. Adrenalectomy should be considered as an option for cases that are good surgical candidates. References The safe use of this drug has not been evaluated in 1. Feßler AT, Schuenemann R, Kadlec K, et al. Methicillin-resistant Staphylococcus aureus (MRSA) lactating dogs and males intended for breeding. and methicillin-resistant Staphylococcus pseudintermedius (MRSP) among employees and in the Vet Microbiol ADVERSE REACTIONS: The most common adverse environment of a small animal hospital. . 2018;221:153-158. reactions reported are poor/reduced appetite, 2. Somayaji R, Priyantha MA, Rubin JE, Church D. Human infections due to Staphylococcus vomiting, lethargy/dullness, diarrhea, elevated liver pseudintermedius, an emerging zoonosis of canine origin: report of 24 cases. Diagn Microbiol Infect enzymes, elevated potassium with or without de- Dis. 2016;85(4):471-476. creased sodium, elevated BUN, decreased Na/K ratio, weakness, elevated creatinine, shaking, and 3. Singh A, Walker M, Rousseau J, Monteith GJ, Weese JS. Methicillin-resistant staphylococcal renal insufficiency. Occasionally, more serious contamination of clothing worn by personnel in a veterinary teaching hospital. Vet Surg. reactions, including severe depression, hemorrhagic 2013;42(6):643-648. diarrhea, collapse, hypoadrenocortical crisis or 4. Grönthal T, Moodley A, Nykäsenoja S, et al. Large outbreak caused by methicillin resistant adrenal necrosis/rupture may occur, and may result Staphylococcus pseudintermedius ST71 in a Finnish veterinary teaching hospital—from outbreak in death. control to outbreak prevention. PLoS One. 2014;9(10):e110084. 5. Weese JS, Faires M, Rousseau J, Bersenas AM, Mathews KA. Cluster of methicillin-resistant Staphylococcus aureus colonization in a small animal intensive care unit. J Am Vet Med Assoc. 2007;231(9):1361-1364. 6. Stull JW, Weese JS. Hospital-associated infections in small animal practice. Vet Clin North Am Small Anim Pract. 2015;45(2):217-233. Distributed by: Dechra Veterinary Products 7015 College Boulevard, Suite 525 Overland Park, KS 66211 Suggested Reading VETORYL is a trademark of Morris DO, Loeffler A, Davis MF, Guardabassi L, Weese JS. Recommendations for approaches Dechra Ltd. © 2015, Dechra Ltd. to methicillin-resistant staphylococcal infections of small animals: diagnosis, therapeutic NADA 141-291, Approved by FDA considerations and preventative measures: Clinical Consensus Guidelines of the World Association for Veterinary Dermatology. Vet Dermatol. 2017;28(3):304-e69.

40 cliniciansbrief.com May 2019 reat eir yperadrenocorticis. Help Restore Their Vitality.

Prior to treatment with VETORYL Capsules

Following 3 months of treatment with VETORYL Capsules

VETORYL Capsules are the only FDA-approved treatment for pituitary- dependent and adrenal-dependent hyperadrenocorticism in dogs (Cushing’s syndrome). They contain the active ingredient trilostane, which blocks the excessive production of cortisol.

As with all drugs, side effects may occur. In eld studies and post-approval experience, the most common side effects reported were: anorexia, lethargy/depression, vomiting, diarrhea, elevated liver enzymes, elevated potassium with or without decreased sodium, elevated BUN, decreased Na/K ratio, hypoadrenocorticism, weakness, elevated creatinine, shaking, and renal insuf ciency. In some cases, death has been reported as an outcome of these adverse events. Following 9 months of treatment VETORYL Capsules are not for use in dogs with primary hepatic or renal disease, or in pregnant with VETORYL Capsules dogs. Refer to the prescribing information for complete details or visit www.dechra-us.com.

To order, please contact your Dechra representative or call (866) 683-0660. For full prescribing information please visit www.dechra-us.com.

24-hour Veterinary Technical Support available (866) 933-2472. Nonurgent Technical Support available via email [email protected].

NADA 141-291, Approved by FDA CAUTION: Federal law restricts this drug to use by or on the order of licensed veterinarian. Vetoryl is a registered trademark of Dechra Limited. Dechra is a registered trademark of Dechra Pharmaceuticals PLC. A

See page 40 for product information summary. FROM PAGE TO PATIENT

Survival to Discharge or Transfer in Stuporous or Comatose Dogs & Cats

Mark Troxel, DVM, DACVIM (Neurology) Massachusetts Veterinary Referral Hospital Woburn, Massachusetts

In the Literature Because an after-hours clinic was used, only short-term prog- Parratt CA, Firth AM, Boag AK, Allison GF, noses (often <14 hours before transfer the following morning but up to 60 hours for weekend admissions) were examined. Boysen SR. Retrospective characterization of Overall, short-term prognosis was poor, with a high mortality coma and stupor in dogs and cats presenting rate for both comatose (dogs, 79.4%; cats, 86.4%) and stupor- to a multicenter out-of-hours service (2012– ous (dogs, 62.5%; cats, 78.5%) patients. This mortality rate included a high percentage of patients that were euthanized at 2015): 386 animals. J Vet Emerg Crit Care. or soon after admission (dogs, 43%; cats, 61%). Of patients for 2018;28(6):559-565. which treatment was attempted, 46% of dogs and 41.2% of cats survived to transfer or discharge. Hypoglycemia was the most common etiology in patients that were successfully FROM THE PAGE … transferred.

Stupor describes a state in which patients are responsive only to There were 2 significant limitations to this study. First, although noxious stimuli (eg, pinching of toes with a hemostat), whereas a definitive diagnosis was listed for many of the patients, it is coma describes a state in which patients are unresponsive even possible some were misclassified, as investigators were review- to noxious stimuli. The aim of this retrospective study was to ing medical records retrospectively. For example, etiology was characterize coma versus stupor in dogs and cats. recorded as cerebrovascular accident or brain tumor for several dogs and cats, but there is no indication of advanced imaging Records were evaluated from an after-hours clinic in which having been performed. Chihuahuas (n = 13) were also report- patients were transferred to another daytime hospital the follow- edly overrepresented; this breed has a predisposition for brain ing morning or at the beginning of the following week for week- malformation (eg, congenital hydrocephalus) and noninfectious end admission. Patients with an undetermined cause of stupor or inflammatory encephalitis, yet neither of these disorders were coma were excluded. Traumatic brain injury was determined to listed as a possible etiology. Second, only the short-term prog- be the most common cause of stupor or coma. Other common nosis could be determined in this study. Additional studies are etiologies included hypoglycemia, shock, renal or hepatic dys- needed to more accurately characterize the etiology and evalu- function, intoxication, seizures, and neoplasia. ate long-term prognosis for these patients.

42 cliniciansbrief.com May 2019 Raising the Standard of Care in Animal Housing

Mason Company’s Fiberglass Cages are part of Fear Free’s Preferred Product Program.

… TO YOUR PATIENTS Molded, solid-surface fiberglass cage bodies Key pearls to put into practice: provide animals with a quieter, warmer and softer environment than cold, loud, and The Modified Glasgow Coma Scale is recommended to help establish initial prognosis for comatose and institutional-looking metal cages. 1stuporous patients. Serial Modified Glasgow Coma Scale scores may also be used in individual patients to monitor improvement or decline.1-3

Prognosis for stuporous or comatose patients with traumatic brain injury is guarded to poor; aggressive 2treatment is crucial to increase the chance for a successful outcome. Treatment measures can include Quiet Cottages™ administration of hyperosmolar agents (eg, mannitol, • Provide a more inviting environment hypertonic saline), intravenous fluid resuscitation and for surgery recovery to speed healing. restoration of normal blood pressure, oxygenation, • Contemporary look and feel. control of blood glucose (hyperglycemia exacerbates • Available in various sizes, can be neuronal necrosis), pain management, head elevation, configured to your exact needs anticonvulsants (if indicated), and/or other supportive • Available with or without individual measures. Corticosteroids are contraindicated in built-in drains to ensure sanitary traumatic brain injury patients.4-7 conditions. • Optional portals and removable Acute, nontraumatic stupor or coma is frequently dividers for housing flexibility. associated with hypoglycemia, renal or liver 3dysfunction, or electrolyte derangements (eg, Fiberglass Cat Suites hypoadrenocorticism). Point-of-care testing The future of cat housing! (particularly packed cell volume/total solids, blood • Designed around best practices glucose, BUN, creatinine, electrolytes), fluid as identified by Fear Free PetsSM, resuscitation, and restoration of normotension are universities and the “Association of critical. Shelter Veterinarians” guidelines to specifically reduce stress in cats. References • Horizontal wire reduces fear and 1. Ash K, Hayes GM, Goggs R, Sumner JP. Performance evaluation and validation of the animal trauma triage score and Modified Glasgow Coma Scale with white powder-coated wire creates suggested category adjustment in dogs: a VetCOT registry study. J Vet Emerg a softer appearance. Crit Care (San Antonio). 2018;28(3):192-200. 2. Platt SR, Radaelli ST, McDonnell JJ. The prognostic value of the Modified • Translucent ceiling lets light into Glasgow Coma Scale in head trauma in dogs. J Vet Intern Med. 2001;15(6):581- what were historically dark cages. 584. • MagnaLatch provides quiet, simple 3. Sharma D, Holowaychuk MK. Retrospective evaluation of prognostic indicators in dogs with head trauma: 72 cases (January-March 2011). J Vet and effective latching. Emerg Crit Care (San Antonio). 2015;25(5):631-639. • Fiberglass sides do not show 4. Kuo KW, Bacek LM, Taylor AR. Head trauma. Vet Clin North Am Small Anim Pract. 2018;48(1):111-128. reflections like stainless steel can. 5. Platt S, Freeman C, Beltran E. Canine head trauma: an update. In Pract. • Litter area separated by a portal door. 2016;38(1):3-8. • Living area includes a removable shelf. 6. Sande A, West C. Traumatic brain injury: a review of pathophysiology and management. J Vet Emerg Crit Care (San Antonio). 2010;20(2):177-190. 7. Syring RS, Otto CM, Drobatz KJ. Hyperglycemia in dogs and cats with head trauma: 122 cases (1997-1999). J Am Vet Med Assoc. 2001;218(7):1124-1129.

May 2019 cliniciansbrief.com 43 (800) 543-5567 www.MasonCo.com | [email protected]

FearFreeAd_VERTICAL_F4PP.indd 1 4/2/19 2:58 PM FROM PAGE TO PATIENT

… TO YOUR PATIENTS Hemoabdomen in Key pearls to put into practice:

Large vs Small Dogs Hemangiosarcoma and other malignancies are more prevalent 1than other conditions as the cause of SH in dogs. Elke Rudloff, DVM, DACVECC, cVMA Small dogs with SH may have a Lakeshore Veterinary Specialists lower prevalence of hemangio- Glendale, Wisconsin 2sarcoma than large dogs. Abdominal ultrasonography and/ or CT may provide the owner with In the Literature 3information on source and extent of lesions that can aid in decision- Fleming J, Giuffrida MA, Runge JJ. Anatomic site and etiology making for a pet with SH. of hemorrhage in small versus large dogs with spontaneous *Prevalence identifies the proportion of subjects hemoperitoneum. Vet Surg. 2018;47(8):1031-1038. that have a condition at or during a period of time. This is different from incidence, which identifies the proportion or rate of subjects that develop a condition during a period of time.

FROM THE PAGE … References 1. Pintar J, Breitschwerdt EB, Hardie EM, Spontaneous hemoperitoneum (SH) can occur as a result of a ruptured mass Spaulding KA. Acute nontraumatic hemoabdomen in the dog: a retrospective (neoplastic or nonneoplastic), organ torsion, organ necrosis, and/or coagulopathy. analysis of 39 cases (1987-2001). J Am Anim Malignant neoplasia has been reported to be the most common cause of SH in dogs.1 Hosp Assoc. 2003;39(6):518-522. 2. Hammond TN, Pesillo-Crosby SA. Prevalence Results from a few retrospective reviews of dogs with SH have led some clinicians of hemangiosarcoma in anemic dogs with a to advise pet owners that the potential for malignancy is high in SH patients with a splenic mass and hemoperitoneum requiring a transfusion: 71 cases (2003–2005). J Am Vet Med splenic tumor.1-3 Although making this recommendation may be intended to help Assoc. 2008;232(4):553-558. owners decide whether they should proceed with emergency surgery or euthanasia, 3. Lux CN, Culp WT, Mayhew PD, Tong K, Rebhun RB, Kass PH. Perioperative outcome in dogs it should be noted that these studies reported on a small number of dogs of different with hemoperitoneum: 83 cases (2005-2010). J Am Vet Med Assoc. 2013;242(10):1385-1391. sizes.

Dogs that had undergone diagnostic testing and had SH unrelated to a coagulopathy (n = 637) were evaluated to determine whether the anatomic source of hemorrhage differed between small (≤44.1 lb [≤20 kg]) and large (>44.1 lb [>20 kg]) dogs. The authors found that, although the most common source of hemorrhage in dogs of all sizes was from the spleen, the prevalence* of splenic-related SH was greater in large dogs. Hemangio- sarcoma was less prevalent in small dogs than in the general population of dogs with bleeding splenic tumors. It was also determined that dogs with nonsplenic causes of SH were less likely to undergo surgery.

These results illustrate that a diagnosis or prognosis ultimately cannot be provided without the expense of advanced imaging and surgery. Although statistics can help answer direct questions from the owners of a critically ill pet, it is important to consider the individual patient.

44 cliniciansbrief.com May 2019 BEST MEDICINE PRACTICES FOR FLEA CONTROL Sponsored by Merck Animal Health

Achieving pet owner compliance with veterinarian-recommended flea counts within 7 days and 100% at 5 flea and tick prevention can be di icult. Owners may be reluctant 12 weeks posttreatment. to treat all household pets, particularly those the owner perceives C as low risk for infestation. A recent study found owners who do Best medicine practices include making purchase flea and tick preventives o en do not adhere to the the best recommendations to veterinary patient owners. The combination of 1 recommended duration of protection. easier, less frequent dosing of flea and tick preventives increases the likelihood A C owners need to obtain a preventive pet owners will comply with veterinarian O C product and using a product that is easier recommendations. ■ Educating owners on infestation risks to administer) may help owners achieve a (eg, dermatologic, infectious, zoonotic better rate of compliance.1 Less frequent diseases) can help owners understand administration of flea and tick preven- REERENCE the need for prevention. tives may make it easier for owners to 1. Lavan RP, Tunceli K, Zhang D, Normile D, meet veterinary recommendation to treat Armstrong R. Assessment of dog owner It is key that owners understand all household pets, rather than restricting adherence to veterinarians’ flea and tick prevention recommendations in the United e ective control of fleas and ticks treatment to just one or two pets. States using a cross-sectional survey. Parasit requires treatment of all dogs and cats Vectors. 2017;10(1):284. 2. Dryden MW, Smith V, Bennett T, Math L, in the house, and that treatment is not A recent study showed that dog owners Kallman J, Heaney K, Sun F. E icacy of contingent on the amount of time a pet who obtained a flea and tick preventive fluralaner flavored chews (Bravecto®) administered to dogs against the adult cat spends outdoors, as infestation can be with a longer-acting duration (ie, 12 ﬂ e a , Ctenocephalides felis felis and egg spread from other pets in the house- weeks) purchased more flea and tick production. Parasit Vectors. 2015;8:364. 3. Dryden MW. Flea and tick control in the 21st hold, free-roaming dogs and cats, and preventives in a year than those who century: challenges and opportunities. Vet some urban wildlife. Owners should also obtained shorter-acting duration (ie, Dermatol. 2009;20:435-440. 3 4. Lavan RP, Armstrong R, Normile D, Zhang D, understand the duration of treatment is 1 month) preventives. Pet owners report Tunceli K. Results from a U.S. dog owner critical, and that a preventive should higher satisfaction with and preference survey on the treatment satisfaction and 2 preference for fluralaner against flea and tick also halt the flea life cycle. A single dose for a flea and tick preventive with infestations. J Vet Sci Technol. 2017;8(3):439. of a 3-month product has been shown to 12-week dosing intervals as compared 5. Dryden MW, Canfield MS, Bocon C, et al. In-home assessment of either topical eliminate flea infestation, but a single with a preventive with 1-month dosing fluralaner or topical selamectin for flea dose of a 1-month product does not.3 intervals.4 Moreover, a recent study control in naturally infested cats in West Central Florida, USA. Parasit Vectors. found a single topical dose of a 12-week 2018;11(1):422. Simplifying flea and tick prevention product provided excellent flea control Copyright © 2019 Intervet Inc., d/b/a Merck Animal (ie, decreasing the frequency in which in cats, achieving >96% reduction in Health, a subsidiary of Merck & Co. Inc. All rights reserved.

Merck_Bravecto_FelinePart2.indd 1 4/17/19 2:05 PM

FROM PAGE TO PATIENT

Antacid Therapy in … TO YOUR PATIENTS Key pearls to put into practice:

Cats with Chronic Although use of PPIs was not associated with a changing rate of CKD progression, 1PPIs may play a role in electrolyte and Kidney Disease bone–mineral metabolism. Because CKD has been demonstrated to negatively affect bone density in dogs,6,7 JD Foster, VMD, DACVIM veterinarians should recognize that bone Friendship Hospital for Animals and mineral disorders might occur in CKD patients8 and be aware of potential Washington, DC negative consequences of PPI therapy.

Routine prophylactic use of antacids in patients with CKD is not indicated.2 Their In the Literature 2use should be reserved for patients with evidence of GI bleeding (eg, melena, iron Gould E, Klos J, Price J, Harris T, Vaden S, Tolbert MK. deficiency) or esophagitis. Retrospective analysis of the effect of acid-suppressant Twice-daily administration of a PPI is the therapy on clinicopathologic parameters of cats with most effective protocol for neutralizing chronic kidney disease. J Feline Med Surg. 2018;20(6):520-527. 3gastric acid in cats with GI ulceration.9 References 1. Lazarus B, Chen Y, Wilson FP, et al. Proton pump inhibitor use and the risk of chronic kidney disease. FROM THE PAGE … JAMA Intern Med. 2016;176(2):238-246. 2. Marks SL, Kook PH, Papich MG, Tolbert MK, Willard Administration of proton pump inhibitors (PPIs) has recently been demonstrated MD. ACVIM consensus statement: support for rational administration of gastrointestinal protectants to dogs to be associated with an increased risk for development of chronic kidney and cats. J Vet Intern Med. 2018;32(6):1823-1840. 1 disease (CKD) in humans. Antacid use is common in veterinary medicine, and 3. Tolbert MK, Olin S, MacLane S, et al. Evaluation of gastric pH and serum gastrin concentrations in many patients are prescribed antacids without clear indication. Although a cats with chronic kidney disease. J Vet Intern Med. common practice among veterinarians, use of antacids to treat nonulcerative GI 2017;31(5):1414-1419. 2 4. McLeland SM, Lunn KF, Duncan CG, Refsal KR, Quimby disease is not warranted. Cats with CKD are thought to be at increased risk for JM. Relationship among serum creatinine, serum GI ulceration; however, several recent studies have shown that these cats rarely gastrin, calcium-phosphorus product, and uremic gastropathy in cats with chronic kidney disease. J Vet develop ulcers and often have more neutral gastric pH than cats with normal Intern Med. 2014;28(3):827-837. kidney function.3,4 Despite this, many veterinarians continue to administer 5. Markovich JE, Freeman LM, Labato MA, Heinze CR. 5 Survey of dietary and medication practices of owners antacids to cats with CKD. of cats with chronic kidney disease. J Feline Med Surg. 2015;17(12):979-983. 6. Shipov A, Shahar R, Sugar N, Segev G. The influence This retrospective medical record review from 2 hospitals examined the effect of chronic kidney disease on the structural and of antacids in cats with CKD. Of the 89 cats included in the review, most (≈70%) mechanical properties of canine bone. J Vet Intern Med. 2018;32(1):280-287. had IRIS stage 1 or 2 CKD. Antacid therapy (H2-receptor antagonists and/or PPIs) 7. Segev G, Meltzer H, Shipov A. Does secondary renal was not found to result in a more rapid progression of kidney disease as osteopathy exist in companion animals? Vet Clin North Am Small Anim Pract. 2016;46(6):1151-1162. compared with cats with CKD not receiving antacids. However, serum sodium 8. Foster JD. Update on mineral and bone disorders in concentration increased over time in cats that received a PPI. In addition, chronic kidney disease. Vet Clin North Am Small Anim Pract. 2016;46(6):1131-1149. concurrent administration of a PPI and H2-receptor antagonist resulted in 9. Šutalo S, Ruetten M, Hartnack S, Reusch CE, Kook PH. The decreased serum magnesium concentration in cats with IRIS stage 1 or 2 CKD. effect of orally administered ranitidine and once-daily or twice-daily orally administered omeprazole on intragas- tric pH in cats. J Vet Intern Med. 2015;29(3):840-846.

May 2019 cliniciansbrief.com 47 NUTRITION EXCHANGE

The Art and Science of Feeding Cats with GI Conditions

Diet is often seen as both the cause and When managing cats with small-bowel the cure for cats with gastrointestinal conditions, what do you look for in a (GI) conditions. Why? therapeutic diet? As veterinarians, we can’t always point to diet as In the past, therapeutic GI diets for cats were being the entire cause of or cure for a GI condition formulated much like many therapeutic GI diets because we often employ multiple therapeutic for dogs, with moderate levels of protein, highly modalities to manage cats with GI conditions. digestible carbohydrate and reduced fat content — However, what we feed cats is critically important what some veterinarians refer to as a “bland” diet. Debra L. Zoran, to both the microflora living in the gut as well as This is not an appropriate strategy for most cats DVM, PhD, DACVIM overall GI tract health. with severe or chronic small intestinal conditions Professor, Department A balance of high-quality nutrients is critical — in fact, for cats with chronic enteropathies, of Small Animal to any good diet because the nutrients need to lymphoma, allergies, or dysbiosis, carbohydrate Clinical Sciences College of Veterinary be digested and absorbed — something that can digestion can be disrupted and the digestive tract Medicine and be much more difficult to achieve with poorer- can be easily overwhelmed. For the reasons cited Biomedical Sciences quality ingredients. Digestibility is especially above, I look for a feline GI diet with high total Texas A&M University important in therapeutic GI diets because we’re digestibility that contains high quality protein College Station, Texas dealing with patients whose intestinal tracts may sources, moderate fat and a low amount be compromised. of carbohydrate.

Why are therapeutic diets formulated You’ve said that high-quality, balanced for dogs and cats with GI conditions nutrients are critical to a good diet. How formulated differently for these can veterinarians determine whether the two species? diet they are recommending contains The nutrient balance of a feline GI diet is different quality protein, fat and carbohydrate? in several ways from a canine GI diet. Here’s why: You have to trust that the manufacturer — based on its track record, its research, its quality control • C ats are obligate carnivores and require higher measures and, in certain instances, the nutritional levels of protein and fat than dogs. Cats may also information it provides — is providing accurate refuse to eat diets that are low in fat because of data. For example, some manufacturers publish decreased palatability. digestibility test results that can help veterinarians • C ats tend to have different GI conditions than determine just how available those nutrients are. dogs. In dogs with GI disease, we worry about the link between high-fat diets and conditions such as severe inflammatory bowel disease (IBD) and protein-losing enteropathy (PLE). However, HIGH we rarely see cats with PLE or other conditions in protein requiring a low fat intestinal diet.1 Feline GI Diet Profile (Small bowel disorders) • C ats don’t digest carbohydrate like dogs do. MODERATE Complex carbohydrates require a significant in fat amount of intestinal enzyme activity and digestive capability. Cats are not designed to be LOW in significant carbohydrate consumers by virtue carbohydrate of their limited digestive enzyme capacity (due to both length of GI tract and number of enzymes available).2 In cats with GI disease, these carbohydrate-digesting enzymes may have 1 Jergens AE, Protein-losing enteropathy (Proceedings), been lost due to inflammation in the intestinal CVC Symposium, Washington wall and changes in the lumen, resulting in DC, 2008. 2 Verbrugghe A, Hesta M. Cats carbohydrate malassimilation and increasing and Carbohydrates: The the potential for dysbiosis or diarrhea from Carnivore Fantasy? Vet Sci, 2017 4(4). carbohydrate intolerance. NUTRITION EXCHANGE Bovine Colostrum Managing Pets with Arleigh Reynolds, Jeff rey Tinsley, DVM DVM, PhD, DACVN Towne North Animal Hospital Enhances Adult Immune Senior Research Scientist GI Conditions Takes San Antonio, Texas Health in Purina Study Nestlé Purina PetCare a Team Eff ort

The immune benefi ts of colostrum bovine colostrum enhanced the similar diversity of microbiota before While obtaining a nutrition history in newborn humans and animals immune response in adult dogs, while and aft er the exercise challenge, is one of the most important steps is well recognized. But what about maintaining their gut microbiota while dogs in the control group saw in managing patients with GI issues, the potential for bovine colostrum diversity and stability. a signifi cantly lower consistency in the fi rst answer an owner gives when supplementation to infl uence immune • While both groups showed a microbial DNA patt erns, suggesting an asked what his or her pet is eating isn’t function in adult dogs? Purina normal post-vaccination increase in alteration in the relative proportion of always the most accurate one. I have researchers studied this question CDV titers, dogs in the colostrum- species and a decrease in diversity of found that probing a litt le further during a 48-week trial in Alaska. supplemented group maintained microbiota. when a GI problem is suspected is post-vaccination titer levels for the worth the time. Trial description entire 48-week period of the study. Conclusions The trial was conducted with 24 adult CDV titers in the control group fell The Purina study showed that The diet history: dogs (Husky crosses with a mean age back to pre-vaccination levels 16 bovine colostrum can enhance the persistence pays of 2.5 years) that were randomized into weeks aft er the administration of the immune function in adult dogs. In our hospital, most patients control and test groups. CDV vaccine. Purina® Pro Plan® Veterinary Diets EN presenting with GI complaints have • During an 8-week “pre-test” period, • Dogs in the test group also had Gastroenteric® Canine and EN Naturals™ experienced vomiting, diarrhea or dry formulas are the only canine dogs in both groups were fed the same signifi cantly higher fecal IgA levels at inappetence for two to three days. therapeutic diets formulated with nutritionally complete diet. the end of the study (see Figure 1). However, the magnitude of a patient’s Successful management of a patient with a GI condition bovine colostrum. • At the end of the “pre-test” period, • Dogs in the colostrum-supplemented problem isn’t always uncovered during can be dependent on a client’s willingness to speak freely serum samples were taken from all group showed stability in the the initial exam room conversation. about what he or she is feeding a pet—including the dogs to measure canine distemper microbial DNA patt erns, refl ecting a In our hospital, the veterinary amount of “people” food the pet eats. virus (CDV) titers. retention of predominant species and technician starts the conversation with • All dogs were then given a canine the owner and makes notes in a fi le distemper virus (CDV) booster vaccine I read before I enter the exam room. Make the exam room a “no working together to help their pets. It’s as part of their routine vaccine While these notes help me understand judgment” zone also gratifying for me to see my patients schedule, then fed either a control or the reason for the visit, I have found I always strive to make clients feel improve. This is why I am so passionate test diet for the next 40 weeks. The Figure 1. Fecal IgA Levels in Control and Colostrum-Supplemented Dogs. that asking clients the same questions comfortable talking about their dogs’ about nutrition and my career. control group continued on the several diff erent ways can yield dietary histories. If they don’t feel they pre-test diet, while the test group additional insights. are being judged, they are much more received the same diet supplemented I recently saw a client with a likely to be forthcoming. with 0.1% commercially obtained, 50 CONTROL COLOSTRUM miniature schnauzer who told the I also try to give my clients options. Key Takeaways spray-dried, bovine colostrum. technician that her dog had stopped While I discuss the possibility of a • Throughout the “test” phase of the eating and had not been herself for the diagnostic workup when the cause of • Canine and feline GI therapeutic 40 trial, dogs in both groups were housed past two days. When the technician took the problem is not clear, I always off er diets are fundamentally diff erent, * and fed individually, given water a dietary history, nothing unusual was a “Plan B” if clients aren’t ready to take with cats requiring higher levels of and exercised 3 days a week via mentioned. As I talked with the client, I that big step. Plan B may include several protein and fat and lower levels of sprint-racing as part of a sled team. 30 learned that, in addition to experiencing diff erent GI modalities, but it almost carbohydrate than dogs. Every 4 weeks, all dogs had blood appetite loss, the dog had vomited always includes transitioning the pet drawn and fecal samples taken. CDV • Feeding a complete and balanced diet several times over the past week. to a therapeutic GI diet. My “go to” for titers were measured every 8 weeks. supplemented with bovine colostrum

IgA (ug/ml) 20 I conducted my examination patients with suspected small-bowel • Two weeks before the conclusion and noted that the dog’s abdomen GI conditions is Purina® Pro Plan® can enhance the immune response in of the study, all dogs were given an was somewhat painful, suggesting Veterinary Diets EN Gastroenteric® adult dogs while maintaining their exercise challenge designed to serve 10 a possible diagnosis of pancreatitis Canine or Feline Formula. These diets gut microbiota diversity and stability. as a model for stress, since stress is or gastroenteritis. At this point, I have high total digestibility and, in known to depress immune function; • A client’s willingness to speak freely specifi cally asked about “people” food, many cases, the diet change is a helpful the challenge consisted of a 10-mile can be key to successful management knowing that inappropriate diet is necessity in my therapeutic plan. I training session performed at an 0 of pets with GI conditions. commonly associated with these stress to owners that if they don’t see average speed of 18 miles per hour. Week 0 Week 40 diagnoses. I learned that my patient improvement within a day or two, was actually eating people food the pet needs to return for additional Trial results Figure 1. Total IgA level in the fecal samples collected at weeks 0 and 40 from dogs fed diets “all the time,” thanks to the client’s testing. By putt ing this advance plan The study showed for the fi rst with or without bovine colostrum. Values are means, with their standard errors represented by mother, who fed the dog a litt le bit in place and taking the time to explain time that feeding a complete and vertical bars (n=12).* Mean values were signifi cantly diff erent from that of the control of everything she ate herself. The what I am asking from them, I fi nd that balanced diet supplemented with group (P<0.05). dog’s owner had no idea this could be owners are more likely to comply. They Satyaraj E, Reynolds A, Pelker R, Labuda J, Zhang P, Sun P. Supplementation of diets with bovine colostrum infl uences immune function in dogs. Brit J Nutr. 2013 June; 110 (12):1-6. detrimental. like knowing that we’re a team that’s NUTRITION EXCHANGE Bovine Colostrum Managing Pets with Arleigh Reynolds, Jeff rey Tinsley, DVM DVM, PhD, DACVN Towne North Animal Hospital Enhances Adult Immune Senior Research Scientist GI Conditions Takes San Antonio, Texas Health in Purina Study Nestlé Purina PetCare a Team Eff ort

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*Conclusion based in part on Kynetec 2017 Veterinary Landscape Canine Gastrointestinal Cases – diagnosis as percent of GI cases. Purina trademarks are owned by Société des Produits Nestlé S.A. FROM PAGE TO PATIENT

Size Is Not a Factor in Standard of Care

Adolf K. Maas III, DVM, DABVP (Reptile & Amphibian), CertAqV Toledo Zoo Toledo, Ohio ZooVet Consulting Bothell, Washington

In the Literature Nau MR, Eshar D. Rostral mandibular fracture repair in a pet bearded dragon (Pogona vitticeps). J Am Vet Med Assoc. 2018;252(8):982-988.

FROM THE PAGE …

Orthopedic injuries can occur in any animal, including nontraditional species. Standard hardware used for domestic animals (eg, plates, screws, intramedullary pins, external fixator apparatus) are often too large to use in many exotic animals, so clinicians must be inventive and use supplies that are commonly available.

This case report exemplifies how success can be obtained by combining best practice methods with creativ- ity. The patient in this report, a lizard weighing approximately 300 g, had a comminuted mandibular fracture requiring stabilization. Because the bone in need of stabilization was only 4 to 6 mm across, the authors

d FIGURE 1 Leopard gecko with external fixator for d FIGURE 2 Cryotherapy site for management of bilateral mandibular fractures. Twenty-seven–gauge cutaneous squamous cell carcinoma in a cockatiel needles were used as intramuscular pins, with epoxy putty used as a connector.

48 cliniciansbrief.com May 2019 repurposed 25-gauge needles, which are commonly found in small mammals, as well as many birds and reptiles; however, veterinary practices, into 0.5-mm external fixator pins and in cases in which intravenous placement may not be feasible, bonded them together using intravenous tubing filled with intraosseous catheterization is simple and effective. Blood dental acrylic. In addition, 36-gauge orthopedic wire cerclage analysis is possible in any species, provided the clinician is loops were used to stabilize a comminuted fragment for familiar with species-specific collection sites. Surgery is only improved alignment. limited by the clinician’s skill and willingness; goldfish can have coelomic masses removed, hamsters may require intestinal Techniques used in standard companion animal practice (see resection and anastomoses, canaries may require fracture Suggested Reading) are immediately relevant in exotic animal repair, and turtles may need to be spayed. practice and should be implemented for exotic animals, as this report illustrates. Although the patient was a small reptile as opposed to a traditional companion animal (eg, cat, dog), … TO YOUR PATIENTS radiographs and a serum chemistry profile were obtained Key pearls to put into practice: prior to anesthesia to conduct an accurate assessment of the injury and evaluate general health. The patient was adminis- Patient size is not a limitation; the only limitation is the tered analgesia, anesthetized, and intubated for orthopedic clinician’s training and skill. repair. Normal activity and appetite returned within 24 hours 1 postoperation. Because reptiles heal slower than mammals, Most veterinary practices have equipment and time was allowed for the patient to heal completely (ie, 5.5 instruments necessary to practice high-quality 2medicine in all patients. months postoperatively), and healing was confirmed radio- graphically before all hardware was removed. The same standard of care can be applied to both domestic companion animals and nontraditional Using alternative materials and modified techniques is not 3species. uncommon in exotic animal medicine.1 Because techniques are mostly universal, modifications rely on knowledge of specific References variations on anatomic themes, as well as applications of dif- 1. Van Wettere AJ, Redig PT, Wallace LJ, Bourgeault CA, Bechtold JE. Mechanical 2 evaluation of external skeletal fixator-intramedullary pin tie-in configurations ferent materials. In many cases, knowledge of applications in applied to cadaveral humeri from red-tailed hawks (Buteo jamaicensis). J Avian one taxon can be easily applied to other taxa.3-5 This practice Med Surg. 2009;23(4):277-285. 2. Patil DB, Adamiak Z, Piórek A. Veterinary interlocking nailing and its can be applied to any situation in nontraditional species medi- augmentation for fracture repair. Pol J Vet Sci. 2008;11(2):187-191. cine. Intravenous catheterization can be performed in most 3. Orosz SE. Clinical considerations of the thoracic limb. Vet Clin North Am Exot Anim Pract. 2002;5(1):31-48. 4. Mitchell MA. Diagnosis and management of reptile orthopedic injuries. Vet Clin North Am Exot Anim Pract. 2002;5(1):97-114. 5. Helmer PJ, Lightfoot TL. Small exotic mammal orthopedics. Vet Clin North Am Exot Anim Pract. 2002;5(1):169-182.

Suggested Reading DeCamp CE, Johnston SA, Déjardin LM, Schaefer SL, eds. Brinker, Piermattei and Flo’s Handbook of Small Animal Orthopedics and Fracture Repair. 5th ed. St. Louis, MO: Elsevier; 2016.

d FIGURE 3 Esophagostomy tube placed in a Russian tortoise for food and medication administration

May 2019 cliniciansbrief.com 49 JOIN THE VOLUNTEER TEAMS WORKING TO ELIMINATE RABIES ACROSS THE GLOBE. FROM PAGE TO PATIENT

Aelurostrongylosis in Cats

Donato Traversa, DVM, PhD, DipEVPC University of Teramo Teramo, Italy

In the Literature Abbate JM, Arfuso F, Gaglio G, et al. Larval survival of Aeluro- strongylus abstrusus lungworm in cat litters. J Feline Med Surg. 2018: 1098612X18811168.

FROM THE PAGE …

Cats infected with the respiratory nematode d FIGURE 1 First stage larvae of Aelurostrongylus abstrusus Aelurostrongylus abstrusus shed first-stage larvae (L1s) in their feces. The gold standard for detecting L1s is the Baermann fecal test.1 Although this test is easy to perform and requires simple equipment, false-negative results may occur due to the prepatency period or intermittent/low larval shedding, and skillful microscopists are necessary for L1 identification.1 Further, the Baermann test detects alive and motile L1s; thus, any factor potentially impacting larval vitality and viability may limit its sensitivity.

Appropriate sampling is crucial for a reliable diagnosis of aelurostrongylosis. Free-living nematodes may confound the diagnosis if the feces are collected from soil (eg, for free-roaming cats); thus, stool samples should be taken from a litter box.

This study evaluated the effects of commercial litters on the survival of A abstrusus L1s in a one-day period (ie, the typical cleaning interval). Clumping and nonclumping clays, silica crystals, and d FIGURE 2 Baermann’s apparatus

Continues h

May 2019 cliniciansbrief.com 51 FROM PAGE TO PATIENT h CONTINUED FROM PREVIOUS PAGE

biodegradable litters were examined under laboratory conditions for their impact on larval survival at regular intervals Research Note: (ie, ≤24 hours). Results indicated that certain factors (eg, litter Caudal Articular type, feces–litter contact time) may limit diagnostic efficiency of the Baermann method. Process Dysplasia

For all litter types used, survival of A abstrusus L1s decreased by approximately 80% after 3 hours and by approximately 100% Thoracic caudal articular process dysplasia has been consid- after 24 hours. This time-dependent decrease was attributed ered a breed-specific disorder in pugs, with a minority of to progressive, litter-induced larval dehydration. The authors affected dogs developing clinical signs of spinal cord dysfunc- note, however, that the laboratory conditions may not reflect tion. This retrospective, cross-sectional study of CT scans of what occurs in the natural setting of a cat’s home. Presence of 271 dogs presented for nonspinal cord-related disease found urine, fecal consistency, and stool not buried in litter may that 97% of presented pugs, as well as 70.4% of French bull- unpredictably prolong larval survival in domestic settings. dogs and 84.1% of English bulldogs, showed evidence of caudal Another important factor influencing larval vitality is variations articular process dysplasia. Prevalence of caudal articular in temperature. The study was performed at 68°F to 73.4°F process aplasia was up to 8-fold higher between T10 and T13 (20°C-23°C; ie, typical indoor home temperatures), although in pugs as compared with French or English bulldogs, possibly samples exposed to colder (eg, cat litter left on balconies, on ter- explaining the higher prevalence of clinical sequelae in pugs. races, in cupboards, in houses without heat or in which heat is Source turned off) or warmer temperatures (eg, litter left outdoors, in Bertram S, Ter Haar G, De Decker S. Caudal articular process dysplasia of thoracic houses without air conditioning or in which air conditioning is vertebrae in neurologically normal French bulldogs, English bulldogs, and pugs: prevalence and characteristics. Vet Radiol Ultrasound. 2018;59(4):396-404. turned off) may still be used for a Baermann test. It should be noted that the longer feces are in litter, the higher the likelihood L1s will die, which may result in false-negative Baermann results.

… TO YOUR PATIENTS Prevalence of caudal articular Key pearls to put into practice: process aplasia was up to The importance of frequent fecal examinations, 8-fold higher between T10 and particularly for cats allowed outdoors, should be 1recognized. T13 in pugs as compared with All cats with respiratory signs should have more than French or English bulldogs. one fresh fecal sample emitted on consecutive days 2examined with the Baermann method. When collecting a fecal sample, owners should be advised to avoid collecting feces deposited hours 3earlier, to clean litter material from the sample, and to bring the sample to the practice as soon as possible.

Reference 1. Traversa D, Di Cesare A. Diagnosis and management of lungworm infections in cats: cornerstones, dilemmas and new avenues. J Feline Med Surg. 2016;18(1):7-20.

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Research Note: Perfectionism & Its Impact on Performance & Mental Health

Marie Holowaychuk, DVM, DACVECC Critical Care Vet Consulting Calgary, Canada

Veterinarians tend to be ambitious and compassionate and found that adaptive perfectionism was highly predictive of have an unwavering desire to provide exceptional care for burnout.5 Disengagement from work and higher levels of patients and pet owners. Along with these tendencies, a pre- exhaustion, both characteristics of professional burnout, sumably high proportion of veterinarians also exhibit perfec- were exhibited in those with both high levels of adaptive tionistic tendencies, which can have positive or negative perfectionism and low levels of maladaptive perfectionism. effects on their performance and psychologic well-being. These findings were attributed to having an increased focus on self-development and professional achievements, which Adaptive perfectionism (ie, perfectionistic striving) is considered likely added to the usual demands of the job.5 a healthy desire to achieve high personal standards and goals, whereas maladaptive perfectionism is characterized by self- Because of the prevailing concern that maladaptive perfec- criticism, fear of failure, and strong feelings of societal pressure tionism is associated with increased distress and reduced to be perfect. Veterinarians exhibiting maladaptive perfection- psychologic well-being, it is important that veterinarians have ism regard mistakes as failures and are rarely satisfied with their an awareness of whether their perfectionistic tendencies are achievements. Maladaptive perfectionism is associated with adaptive (ie, healthy striving) or maladaptive (ie, characterized psychologic distress,1 and a study has shown that students by self-criticism and/or driven by perceived pressure from admitted to medical school exhibiting maladaptive perfection- others). Cognitive behavioral therapy, performed in person ism have increased symptoms of anxiety and depression.2 or using web-based programs, has been shown to improve maladaptive perfectionism and reduce distress, anxiety, and A recent study of 540 Australian veterinarians (23-74 years of depression in adults6,7 and is recommended to help veterinari- age; 64% female) found that triggering stressor events (eg, ans manage their perfectionistic tendencies. n owners not consenting to recommended treatments, carrying out owner wishes that were not in the best interest of the References patient) had a higher likelihood of causing psychologic distress 1. Castro J, Soares MJ, Pereira AT, Macedo A. Perfectionism and negative/positive affect associations: the role of cognitive emotional regulation and perceived in perfectionistic veterinarians. This demonstrates that veteri- distress/coping. Trends Psychiatry Psychother. 2017;39(2):77-87. narians exhibiting perfectionism have an increased vulnerability 2. Seeliger H, Harendza S. Is perfect good? Dimensions of perfectionism in newly admitted medical students. BMC Med Educ. 2017;17(1):206. 3 to distress during morally challenging situations in practice. 3. Crane MF, Phillips JK, Karin E. Trait perfectionism strengthens the negative effects of moral stressors occurring in veterinary practice. Aust Vet J. 2015;93(10):354-360. Perfectionism has also been shown to contribute to higher 4. Hill AP, Curran T. Multidimensional perfectionism and burnout: a meta-analysis. rates of professional burnout.4 However, whether adaptive or Pers Soc Pyschol Rev. 2016;20(3):269-288. 5. Robakowska M, Tyranska-Fobke A, Walkiewicz M, Tartas M. Adaptive and maladaptive perfectionism is a bigger risk factor professionally maladaptive perfectionism and professional burnout among medical laboratory remains unclear, as does the relationship between perfection- scientists. Med Pr. 2018;69(3):253-260. 6. Arpin-Cribbie C, Irvine J, Ritvo P. Web-based cognitive-behavioral therapy for ism and burnout in the workplace. A study that assessed the perfectionism: a randomized controlled trial. Psychother Res. 2012;22(2):194-207. relationship among adaptive and maladaptive perfectionism 7. Chand SP, Chibnall JT, Slavin SJ. Cognitive behavioral therapy for maladaptive perfectionism in medical students: a preliminary investigation. Acad Psychiatry. and professional burnout among medical laboratory scientists 2018;42(1):58-61.

May 2019 cliniciansbrief.com 55 DEPARTMENT h ATEGORYC h PEER REVIEWED

PANCREATICTOP 5 TOP 5 RADIOGRAPHIC VARIANTSBIOPSY

Ron Ofri, DVM, PhD, DECVO HebrewAnthony University Pease, of DVM, Jerusalem MS, DACVR RWesternehovot, VeterinaryIsrael Conference Las Vegas, Nevada

56 cliniciansbrief.com January 2016 nterpretingntemortem radiographs diagnosis can of be difficultpancreatic when disease a lesion is a is not obvious.challenge. Clinicians Histopathol- must IogyAconsider remains anatomic the gold differences standard of diagnosisamong species for pancr and breedseatic neopla- to siaunderstand and pancr whateatitis. to expect Pancreatic on biopsyradiographs provides and a how definitive to differ diag-- nosisentiate of normal pancreatitis, from abnormalassuming a representativeradiographs. sample is obtained. An open or laparo- scopic approach can be made to collect samples.

September 2015 cliniciansbrief.com 57 TOP 5 h DIAGNOSTICS/RADIOGRAPHY h PEER REVIEWED

Both dog size and breed may affect the appearance TOP 5 RADIOGRAPHIC VARIANTS of the thorax. For example, clinicians should not expect the thorax of a Chihuahua and a greyhound 1. Cardiac Silhouette of Cats on Thoracic Radiographs to display the same radiographic appearance. Sim- 2. Cardiac Silhouette of Dogs on Thoracic Radiographs ilarly, a cat should not be compared with a small dog, as geriatric changes to the heart and appear- 3. Kidney Placement & Size in Dogs on Abdominal ance of the abdomen, including renal size, are not Radiographs standard between cats and dogs. 4. Kidney Size in Cats on Abdominal Radiographs Following are the author’s top 5 canine and feline 5. Musculoskeletal Variations in Chondrodystrophic & Large-Breed Dogs radiographic variants.

Cardiac Silhouette of Cats on Thoracic Radiographs Thoracic radiographs are generally difficult A 1 to assess in cats due to age-associated variability. The cardiac silhouette develops increased sternal contact as cats age (Figure 1), with the aorta creating a notch or right-angled appearance that can falsely suggest left atrial enlargement on ventrodorsal projection. The aortic arch may have a rounded appearance on the ventrodorsal projection that can be mistaken for a pulmonary nodule in the left cranial lung lobe (Figure 2).1

Cardiac Silhouette of Dogs on Thoracic Radiographs The cardiac silhouette can appear larger in B 2 small-breed dogs because the heart occu- pies a large amount of thoracic space; conversely, the cardiac silhouette can appear smaller in large- breed dogs (eg, greyhounds) due to the relatively larger size of the thorax (Figure 3).2

In dogs and cats, the vertebral heart score (VHS) system measures the width of the cardiac silhouette (ie, distance from cranial to caudal [ie, short axis] along the estimation of where the atria and

d FIGURE 1 Lateral radiographs of a 2-year-old cat (A) and a ventricles meet) and from the carina of the trachea 9-year-old cat with increased sternal contact of the cardiac to the apex of the heart at its most ventral point silhouette (B) (lines [ie, long axis] should be perpendicular to each other). These measurements are transferred caudally starting at T4 to calculate the VHS (Fig- ure 4, page 60).2 Although this measurement is a VHS = vertebral heart score good general guide, it can be overinterpreted, as

58 cliniciansbrief.com May 2019 cardiac chambers can change size without changing the shape of the cardiac silhouette.3

The average VHS in dogs is approximately 9.5 ± 0.5 with a normal range of 8.7 to 10.7. The measurement can change based on right or left recumbency (see a compilation of breed-specific VHS reference ranges available from Nguyenba in Sug- gested Reading, page 61). Measurements are more useful when diagnosing dilatative forms of cardiac disease and are reported to be less accurate in dogs with cardiac diseases with concentric hypertrophy.3 VHS for cats in right lateral recumbency is 7.3 ± 0.5.4 A VHS >7.9 has a high diagnostic accuracy in distinguishing cats with left-sided cardiac 5 disorders from healthy cats. d FIGURE 2 Ventrodorsal radiograph of a 9-year-old cat with a prominent aortic arch (arrow) Because there are breed differences in VHS measurements, finding a reference range is valuable and can increase accuracy of the assessment.3,6 In a study, A VHS measurements were found to be most accurate in Yorkshire terriers and Cavalier King Charles spaniels.3 Heart size relative to thoracic volume varies among dog breeds and is considered to be primarily due to thorax conformation. In barrel- chested breeds (eg, bulldogs, Boston terriers, Lhasa apsos), the cardiac:thoracic ratio is generally larger than in normal or deep-chested breeds. The VHS system was developed to help address this issue but its efficacy is unclear (seeBenefits & Limitations of Vertebral Heart Scoring, next page).7

Kidney Placement & Size in Dogs B on Abdominal Radiographs Abdominal radiographs have less variabil- 3 ity among dog breeds regarding overall appearance and location of organs. Kidney length has been reported to be 2.98 ± 0.44 times the length of L2 on the ventrodorsal view.8 Still, there are significant differences in renal:L2 size ratios between brachycephalic and dolichocephalic dogs. Small-breed dogs (<22 lb [10 kg]) have been shown to have a significantly higher left kidney:L2 ratio as d FIGURE 3 Relative heart size difference on lateral thoracic compared with large-breed dogs (>66 lb [30 kg]). A radiographs of a normal basset hound (A) and a normal single normal ratio should not be used for all dogs. greyhound (B)

May 2019 cliniciansbrief.com 59 TOP 5 h DIAGNOSTICS/RADIOGRAPHY h PEER REVIEWED

Kidney Size in Cats Musculoskeletal Variations on Abdominal Radiographs in Chondrodystrophic Kidney size varies between intact and neu- & Large-Breed Dogs 4 tered male cats.9 On ventrodorsal radio- 5 Chondrodystrophic musculoskeletal varia- graphs, normal kidney:L2 ratios are 1.9 to 2.6 tions on radiographs are generally based on the (measuring renal length and dividing by the difficulty of obtaining straight lateral and cranio- length of L2) in neutered male cats and 2.1 to 3.2 caudal radiographs of the thoracic limbs (Figure in intact cats (Figure 5).9 6) in chondrodystrophic dogs, whereas large- breed musculoskeletal variations on radiographs are generally based on the difficulty of obtaining straight lateral radiographs of the stifles and tarsi in large-breed dogs. BENEFITS & LIMITATIONS OF VERTEBRAL HEART SCORING Positioning chondrodystrophic dogs for musculoskeletal radiographs can be challenging because of The benefit of VHS is limited because of the wide range of normal values. Normal variable VHS values have been their curved humerus, radius, and ulna. It is gen- determined for several breeds of dogs and cats. One of the erally easier to position the thoracic limbs of large- greatest benefits of VHS, however, is that it allows for the breed dogs as compared with chondrodystrophic comparison of recheck radiographs to monitor disease dogs, but the pelvic limbs (primarily the tarsus progression and response to treatment. Some studies and stifle) may appear oblique due to the large have suggested that subjective heart assessment is better thigh musculature on lateral projections and the 3,7 than VHS at differentiating cardiac disease. Studies have inability to completely extend the coxofemoral also suggested that interobserver variability of VHS can joints. Use of pads or passive restraint (eg, ropes, 10 play an important factor in assessment of heart size. tape) and/or tilting the radiographic tube can help optimize the radiographic image. Literature focused on positioning and minimizing the difficulty in interpreting normal radiographs can be found in Suggested Reading.

Conclusion Radiographs provide a quick overview of the thorax, abdomen, and musculoskeletal structures, but the interpretation can be variable. VHS measurement is a helpful guide for identifying and monitoring heart size changes but is not as accurate as echocardiography to determine the internal architecture and function of the heart. Age changes, breed variation, and neutered versus

d FIGURE 4 VHS measurements in a dog with mitral valve endo- intact status can be associated with radiographic cardiosis and left-sided heart failure. Horizontal and vertical variability. Interpretation of abnormalities should lines are used to approximate the size of the heart and are then be aided by various measurement parameters but superimposed on the vertebral bodies starting at the cranial aspect of the fourth vertebral body. The length is calculated, always combined with clinical signs and physical and the 2 are added together. examination findings.

VHS = vertebral heart score

60 cliniciansbrief.com May 2019 d FIGURE 5 Ventrodorsal radiograph measuring renal size of d FIGURE 6 Lateral radiograph of the right thoracic limb of a normal kidneys in a neutered cat. The longer black line over dachshund with a curved humerus, radius, and ulna n the renal silhouette shows the length of the left kidney, which can be compared with the shorter black line superimposed on the L2 vertebral body.

References 1. Moon ML, Keene BW, Lessard P, Lee J. Age related changes in the 10. Hansson K, Häggström J, Kvart C, Lord P. Interobserver variability of feline cardiac silhouette. Vet Radiol Ultrasound. 1993;34(5):315-320. vertebral heart size measurements in dogs with normal and enlarged 2. Mostafa AA, Berry CR. Radiographic assessment of the cardiac silhou- hearts. Vet Radiol Ultrasound. 2005;46(2):122-130. ette in clinically normal large- and small-breed dogs. Am J Vet Res. 2017;78(2):168-177. Suggested Reading 3. Lamb CR, Wikeley H, Boswood A, Pfeiffer DU. Use of breed-specific Buchanan JW. Vertebral scale system to measure heart size in radio- ranges for the vertebral heart scale as an aid to the radiographic diag- graphs. Vet Clin North Am Small Anim Pract. 2000;30(2):379-393. nosis of cardiac disease in dogs. Vet Rec. 2001;148(23):707-711. Greco A, Meomartino L, Raiano V, Fatone G, Brunetti A. Effect of left vs. 4. Ghadiri A, Avizeh R, Rasekh A, Yadegari A. Radiographic measurement right recumbency on the vertebral heart score in normal dogs. Vet of vertebral heart size in healthy stray cats. J Feline Med Surg. 2008; Radiol Ultrasound. 2008;49(5):454-455. 10(1):61-65. Nguyenba T. Consider the breed when assessing vertebral heart score in 5. Guglielmini C, Baron Toaldo M, Poser H, et al. Diagnostic accuracy dogs. MedVet website. https://www.medvetforpets.com/consider- of the vertebral heart score and other radiographic indices in the breed-assessing-vertebral-heart-score-dogs. Published December 2, detection of cardiac enlargement in cats with different cardiac disor- 2016. Accessed April 2019. ders. J Feline Med Surg. 2014;16(10):812-825. Olive J, Javard R, Specchi S, et al. Effect of cardiac and respiratory cycles 6. Jepsen-Grant K, Pollard RE, Johnson LR. Vertebral heart scores in on vertebral heart score measured on fluoroscopic images of healthy eight dog breeds. Vet Radiol Ultrasound. 2013;54(1):3-8. dogs. J Am Vet Med Assoc. 2015;246(10):1091-1097. 7. Lamb CR, Tyler M, Boswood A, Skelly BJ, Cain M. Assessment of the Sirois M, Anthony E, Mauragis D. Handbook of Radiographic Positioning for value of the vertebral heart scale in the radiographic diagnosis of car- Veterinary Technicians. Clifton Park, NY: Delmar Cengage Learning; diac disease in dogs. Vet Rec. 2000;146(24):687-690. 2010. 8. Lobacz MA, Sullivan M, Mellor D, Hammond G, Labruyere J, Dennis R. University of Florida. Radiographic vets II: dog breeds, normal thorax. Effect of breed, age, weight and gender on radiographic renal size in University of Florida website. http://media.news.health.ufl.edu/misc/ the dog. Vet Radiol Ultrasound. 2012;53(4):437-441. vetmed/gvi/DogBreeds. Accessed March 2019. 9. Shiroma JT, Gabriel JK, Carter RL, Scruggs SL, Stubbs PW. Effect of reproductive status on feline renal size. Vet Radiol Ultrasound. 1999;40(3):242-245.

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Chill Protocol to Manage Aggressive & Fearful Dogs

Renata S. Costa, DVM, MPhil, MANZCVS, GradDipEd Alicia Z. Karas, DVM, MS, DACVAA Stephanie Borns-Weil, DVM, DACVB Cummings School of Veterinary Medicine at Tufts University

Trotman, a 10-year-old, 100.3-lb (45.5-kg), toward team members. Thus, the Chill Protocol* to be neutered male German shepherd dog, was administered at home prior to Trotman’s follow-up appointment was prescribed to decrease patient and owner stress presented for oral examination after the owners noted blood in his mouth. No other apparent health problems were reported. TREATMENT AT A GLANCE: CHILL PROTOCOL

h Gabapentin (20-25 mg/kg PO) should be administered the evening Physical Examination before the scheduled appointment. The physical examination was limited due to fear- h induced aggression, which was demonstrated by A combination of gabapentin (20-25 mg/kg PO) and melatonin (small dogs, 0.5-1 mg PO; medium dogs, 1-3 mg PO; large dogs, Trotman’s low body posture, tucked tail, growling, 5 mg PO) should be administered at least 1 to 2 hours before the and lunging when approached by team members. scheduled appointment. His owners were able to open his mouth and allow visualization of a 2-cm mass in the buccal tissue at h Acepromazine (0.025-0.05 mg/kg OTM) should be administered the level of the right 3rd molar. 30 minutes before the scheduled appointment.

*The Chill Protocol is a relaxation protocol developed to manage fearful and aggressive Oral examination, thoracic radiography, abdomi- dogs branded by the authors at Cummings School of Veterinary Medicine at Tufts University, where it has been routinely administered to dogs and cats prior to medical appointments nal ultrasonography, and resection/biopsy of the and to facilitate anesthesia since 2014. mass were recommended but could not be per- OTM = oral transmucosal formed due to Trotman’s fear-induced aggression

May 2019 cliniciansbrief.com 63 CASE IN POINT h BEHAVIOR h PEER REVIEWED

levels and allow team members to safely handle supports its use. Melatonin is a naturally occurring the patient for diagnostic investigation of the hormone produced by the pineal gland. Exogenous mass. melatonin has been shown to reduce pre- and postoperative anxiety in humans,6,7 and its calming Chill Protocol effects and overall safety may benefit dogs with The Chill Protocol is a combination of orally fear-motivated aggression and/or anxiety. Ace- administered medications to facilitate procedural promazine elicits behavior-modifying effects (ie, management of animals that exhibit signs of anxi- tranquilization, sedation) in animals and has syn- ety and/or aggression. The protocol consists of ergistic effects with other sedatives, anxiolytics, at-home administration of gabapentin, melatonin, and opioids that produce calming effects.8,9 and oral transmucosal (OTM) acepromazine (10 mg/mL injectable formulation) prior to a medical Trotman received gabapentin (22 mg/kg PO) the appointment (see Treatment at a Glance: Chill night before his follow-up appointment and a com- Protocol, previous page). Gabapentin and mela- bination of gabapentin (22 mg/kg PO), melatonin tonin can be given with a small amount of food, and (5 mg PO), and acepromazine (0.04 mg/kg OTM) acepromazine should be administered oral trans- at least 30 minutes prior to the appointment mucosally via syringe for mucosal absorption. (Table). The timing of administration of the Chill Protocol is essential, as it is important that medica- Gabapentin has anxiolytic, sedative, analgesic, tions take effect prior to the stimulation caused by and anticonvulsive properties.1-5 Oral gabapentin the trip to the hospital. Trotman’s owners were causes anxiolysis and sedation in humans and advised of the potential for mild-to-heavy sedation reduces fear responses in cats.1-4 Although pub- and weakness or incoordination and the need for lished data on gabapentin’s use for anxiolysis and supervision. The duration of sedation is variable but sedation are lacking, anecdotal clinical experience can last up to 24 hours, which is normal and not harmful, whereas severe stress can have lasting effects and may leave a dog tired and depressed, TABLE reduce immune function, and result in other physical sequelae following exposure to the stressor.10 CHILL PROTOCOL ADMINISTERED TO TROTMAN (100.3 LB [45.5 KG]) Outcome Trotman arrived at the hospital moderately sedated and ataxic but still ambulatory and wear- ing a muzzle. He gave a low growl in response to Drug Evening 1 to 2 Hours 30 Minutes Prior to Prior to Prior to team members entering the examination room. Examination Examination Arrival for Hydromorphone (0.1 mg/kg IM) was adminis- (Dose) (Dose) Examination tered while Trotman was under minor restraint, (Dose) and the muzzle was removed in case of vomiting. He was left in the examination room with the own- Gabapentin 1000 mg PO 1000 mg PO – ers for 20 minutes while the hydromorphone took Melatonin – 5 mg PO – effect (sedation should be deep enough to allow further manipulations to be performed without Injectable – – 2 mg OTM the patient struggling). An intravenous catheter acepromazine was then easily placed in a lateral saphenous vein while Trotman was conscious but sedate. He offered no resistance to being remuzzled, lifted to OTM = oral transmucosal a gurney, and taken to radiology, where he was

64 cliniciansbrief.com May 2019 positioned for thoracic radiography and subsequently transported to undergo ultrasonography. TAKE-HOME MESSAGES An hour later, Trotman was induced with propofol (1.5 mg/kg), intubated, and anesthetized with h The Chill Protocol aids in reducing fear, anxiety, and sevoflurane for oral examination and dental pro- aggressive behavior in animals to facilitate safer, less cedures, which were performed over the course of stressful handling during physical examinations, blood draws, and noninvasive diagnostic procedures. 2 hours. Vital parameters remained within normal

limits. Recovery from anesthesia was uneventful. h Additional injectable drugs (eg, opioids, α2 agonists, Owners continued administration of the Chill Pro- anesthetics) are often required to provide adequate tocol for subsequent medical appointments due to analgesia and sedation for certain patients or more its calming effects, with no adverse events noted at invasive procedures. home or in the hospital. h The prescribing clinician is responsible for awareness of the patient’s general health condition and when Conclusion Chill Protocol administration might be contraindicated The Chill Protocol provided adequate anxiolysis or require administration at a lower dose. and sedation to allow for safe management of a dog h Chill Protocol duration is approximately 4 to 6 hours. with fear-induced aggression without significant Redosing may be required if the patient is not side effects. The Chill Protocol can be prescribed to expected at the hospital until later or remains at the healthy patients that are known to be aggressive, hospital all day. fearful, and/or anxious during hospital visits (see h Timing of drug administration and owner compliance Take-Home Messages). are essential for successful treatment. n

The timing of administration of the Chill Protocol is essential, as it is important that medications take effect prior to the stimulation caused by the trip to the hospital.

References 1. Clarke H, Kirkham KR, Orser BA, et al. Gabapentin reduces preopera- 6. Andersen LP, Werner MU, Rosenberg J, Gögenur I. A systematic review tive anxiety and pain catastrophizing in highly anxious patients prior of peri-operative melatonin. Anaesthesia. 2014;69(10):1163-1171. to major surgery: a blinded randomized placebo-controlled trial. Can J 7. Hansen MV, Halladin NL, Rosenberg J, Gögenur I, Møller AM. Melatonin Anesth. 2013;60(5):432-443. for pre- and postoperative anxiety in adults. Cochrane Database Syst 2. Ménigaux C, Adam F, Guignard B, Sessler DI, Chauvin M. Preoperative Rev. 2015;4:CD009861. gabapentin decreases anxiety and improves early functional recovery 8. Monteiro ER, Junior AR, Assis HM, Campagnol D, Quitzan JG. Compar- from knee surgery. Anesth Analg. 2005;100(5):1394-1399. ative study on the sedative effects of morphine, methadone, butor- 3. Chouinard G, Beauclair L, Belanger MC. Gabapentin: long-term anti- phanol or tramadol, in combination with acepromazine, in dogs. Vet anxiety and hypnotic effects in psychiatric patients with comorbid Anaesth Analg. 2009;36(1):25-33. anxiety-related disorders. Can J Psych. 1998;43(3):305. 9. Hekman JP, Karas AZ, Sharp CR. Psychogenic stress in hospitalized 4. Pankratz KE, Ferris KK, Griffith EH, Sherman BL. Use of single-dose oral dogs: cross species comparisons, implications for health care, and the gabapentin to attenuate fear responses in cage-trapped community challenges of evaluation. Animals (Basel). 2014;4(2):331-347. cats: a double-blind, placebo-controlled field trial. J Feline Med Surg. 10. Siracusa C, Manteca X, Cerón J, Martinez-Subiela S. Periopera- 2018;20(6):535-543. tive stress response in dogs undergoing elective surgery: Varia- 5. Guedes AGP, Meadows JM, Pypendop BH, Johnson EG, Zaffarano B. tions in behavioural, neuroendocrine, immune and acute phase Assessment of the effects of gabapentin on activity levels and owner- responses. Anim Welfare. 2008;17(3):259-73. perceived mobility impairment and quality of life in osteoarthritic geriatric cats. J Am Vet Med Assoc. 2018;253(5):579-585.

May 2019 cliniciansbrief.com 65 From Clinician’s Brief on Social Media

WE ASKED …

What preanesthetic tests, if any, Do you charge a fee when a do you require in patients with a pet owner requests you call in heart murmur? a prescription to an internet

“We recommend an echocardiogram with a cardiologist. We pharmacy? cannot require it, but most pet owners agree to it.”—Sarah H

“Blood work, urine samples, radiographs, pro B-type natriuretic peptide test, and potential referral to a cardiologist.”—Kim S

“Blood work is required to see if there are any other risk factors. Thoracic radiographs and echocardiogram and/or consultation are recommended.”—Anthony T “Radiographs, electrocardiogram, and heart ultrasound.”—Alyx L No Yes Do you use NSAIDs for long-term pain management in cats?

57% No

43% Yes

“For geriatric cats, I consider NSAIDs as part of their food and not medication.”—Sabine S “I do not deal with internet pharmacies. If the pet owner “Depends on the cat’s quality of life and renal function.” wants a prescription, I write one and give it to them. —Danielle S They mail it to the pharmacy of their choice. I charge $6 “In theory, yes. In practice, rarely.”—Susan E to handle the paperwork.”—Luke L

“At very low doses.”—Ashley B “I would love to, but I think it would make way too many people angry.”—Katy H

“Not yet, but I might if it starts taking too much of my FOLLOW US time.”—Christopher H

“Yes. The time it takes the team member to look at the facebook.com/cliniciansbrief file, confirm the correct medication, complete the prescription, and send to the pharmacy must be paid for.” @CliniciansBrief —Shona M clinicians.brief

66 cliniciansbrief.com May 2019 PRACTICE HOTLINE

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Free Continuing Education 2019 AAHA Dental Care Guidelines Credit for Practice Managers AAHA (aaha.org) has released an update to the 2013 The Veterinary Hospital Managers Association (vhma.org) has AAHA Dental Care Guidelines for Dogs and Cats. The announced that members can now receive continuing education cred- 2019 guidelines offer an approach to support com- its at no charge when they complete the Partners for Healthy Pets panion animal practices in improving the oral health (partnersforhealthypets.org) Preventive Healthcare Certificate of patients and include: Program. According to the Certified Veterinary Practice Manager h An expanded and updated discussion of com- Certification Board, managers who complete the certificate program monly performed veterinary dental procedures, can apply 9 continuing education credits toward the Certified Veteri- with photos illustrating oral pathology and thera- nary Practice Manager certificate program requirements. RACE credits peutic techniques are available. h Criteria for periodontal disease staging h Discussion of the importance of addressing pain The program includes 10 modules that examine specific topics and and stress in dental patients explore the role they play in improving pet owner compliance and h Tips for communicating to pet owners the impor- enhancing the level and quality of patient care. Among the topics tance and rationale behind specific dental and oral highlighted are opportunity surveys to identify unmet needs, guid- procedures ance in implementing preventive healthcare guidelines, strategies for building an online presence using internet marketing and social The guidelines also cover dental terminology; anat- media, approaches to improving communication, and the essentials omy and pathology; strategies for prevention of den- for creating a feline-friendly practice. For more information, visit tal disease; patient assessment, evaluation, and doc- partnersforhealthypets.org.—Press Release 2/2019 umentation; dental procedures; considerations for anesthesia, sedation, and analgesia; how to address pain; the role of veterinary nurses and veterinary Companion Animal Health Stance Analyzer assistants; requirements for facilities, equipment, Companion Animal Health (companionanimalhealth.com) and operator safety; and pet owner communication has announced the launch of the Stance Analyzer, a diagnostic and education. product that provides weight-bearing data and support of early lameness detection with objective data that translate into a visual The guidelines are available at aaha.org.—Press report that can be given to the pet owner. The Stance Analyzer is Release 4/2019 n designed for use during wellness examinations for early lameness detection, during problem visits to support an accurate diagnosis, and as a recheck tool when a pet is engaged in a plan of care. SEND INFORMATION Learn more at companionanimalhealth.com/page/stance-analyzer. FOR PRACTICE HOTLINE TO —Press Release 3/2019 [email protected]

May 2019 cliniciansbrief.com 67 PRACTICE MARKETPLACE

68 cliniciansbrief.com May 2019 May 2019 cliniciansbrief.com 69 IMMITICIDE® STERILE POWDER (MELARSOMINE DIHYDROCHLORIDE) Brief Summary: Before Using IMMITICIDE, please consult the product insert, a summary of which follows. CAUTION Federal law restricts this drug to use by or on the order of a licensed veterinarian.

WARNING IMMITICIDE should be administered by deep intramuscular injection in the lumbar (epaxial) muscles (between L3 - L5) ONLY. DO NOT USE IN ANY OTHER MUSCLE GROUP. DO NOT USE INTRAVENOUSLY. Care should be taken to avoid superficial injection or leakage. (See SAFETY).

INDICATIONS Disease Classification: It is vital to classify the severity of heartworm IMMITICIDE Sterile Power is indicated for the treatment of stabilized disease to apply the appropriate dosage regime for IMMITICIDE. See full Class 1, 2, and 3 heartworm disease caused by immature (4-month-old, product insert for Heartworm Disease Classification criteria. stage L5) to mature adult infections of Dirofilaria immitis in dogs. See full Class 1 and 2: IMMITICIDE should be given in two intramuscular package insert for Heartworm Disease Classification. injections of 2.5 mg/kg, 24 hours apart. Four months following treatment, a second treatment series (2.5 mg/kg twice, 24 hours apart) can be elected. CONTRAINDICATIONS Class 3: Alternate Dosing Regime: Dogs with severe (Class 3) heartworm IMMITICIDE is contraindicated in dogs with very severe (Class 4) disease should be stabilized prior to treatment and then dosed heartworm disease. Patients in this category have Caval Syndrome (D. intramuscularly in the lumbar (L3 - L5) muscles with a single injection of immitis present in the venae cavae and right atrium). 2.5 mg/kg then approximately 1 month later with 2.5 mg/kg administered twice, 24 hours apart. WARNINGS (See boxed Warning). For use in dogs only. Safety for use in breeding SAFETY animals and lactating or pregnant bitches has not been determined. IMMITICIDE has a low margin of safety. A single dose of 7.5 mg/kg (3X the recommended dose) can result in pulmonary inflammation, HUMAN WARNINGS edema, and death. Symptoms of overdose (2x recommended dose) may Keep this and all medications out of the reach of children. Avoid human include excessive salivation, panting, restlessness, fever, vomiting and exposure. Wash hands thoroughly after use or wear gloves. Potentially diarrhea. These symptoms were seen in the clinical trials and all signs irritating to eyes. Rinse eyes with copious amounts of water if exposed. resolved within 24 hours. Symptoms of up to 3x the recommended dose Consult a physician in cases of accidental exposure by any route (dermal, included tremors, lethargy, unsteadiness, restlessness, panting, shallow oral, or by injection). and labored breathing, pulmonary inflammation, edema, and vomiting which progressed to respiratory distress, collapse, and death. Daily PRECAUTIONS administration of 2X and 3X the recommended dose for 14 days caused Dogs with heartworm disease are at risk for post-treatment pulmonary renal damage in healthy dogs. thromboembolism (death of worms which may result in fever, weakness, and coughing). Dogs with severe pulmonary arterial disease have an In Case of Overdosage: increased risk and may exhibit more severe signs (dyspnea, hemoptysis, BAL in Oil Ampules (Dimercaprol Injection, USP) [Akorn, San right heart failure and possibly death). Dogs should be restricted from Clemente, California, at 1-800-223-9851] is reported in the literature to exercise after treatment. Studies indicate that adverse reactions may be an antidote for arsenic toxicity and was shown in one study to reduce occur after the second injection in the series even if no problems were the signs of toxicity associated with over-dosage of IMMITICIDE. The encountered with the first injection. All patients should be closely efficacy of IMMITICIDE may be reduced with co-administration of BAL. monitored during treatment and for up to 24 hours after the last injection. ADVERSE REACTIONS (SIDE EFFECTS) Special Considerations for Class 3 dogs: Following stabilization, severely In clinical field trials, the most common reactions seen in dogs ill (Class 3) dogs should be treated according to the alternate dosing treated with IMMITICIDE were coughing/gagging, depression/ regime in an attempt to decrease post-treatment mortality associated with lethargy, anorexia/inappetence, fever, lung congestion, and vomiting. thromboembolism. Post-treatment mortality due to thromboembolism Hypersalivation and panting occurred more rarely, however, these and/or progression of the underlying disease may occur in 10 to 20% of signs may occur within 30 minutes of injection and may be severe. the Class 3 patients treated with IMMITICIDE. Hospitalization post- Significant irritation was also observed at the intramuscular injection treatment and strict exercise restriction are recommended. If the alternate sites, accompanied by pain, swelling, tenderness, and reluctance to move. dosing regime is used, expect increased injection site reactions on the Generally, injection site reactions were mild to moderate in severity side receiving the second injection since the skeletal muscles at the first and recovery occurred in 1 week to 1 month, however, firm nodules injection site may not have fully recovered (healed). If persistent swelling can persist indefinitely. Avoid superficial or subcutaneous injection and is present at 1 month, the second injections may be delayed for several leakage. Heartworm disease may cause death in dogs with or without weeks up to 1 month. treatment, especially in the Class 3 dogs.

Special Considerations for Older Dogs: In clinical field trials, dogs 8 Post Approval Experience: There have also been rare reports of paresis years or older experienced more post-treatment depression/lethargy, and paralysis in dogs following administration of IMMITICIDE. anorexia/inappetence, and vomiting than younger dogs. The information provided here is not comprehensive. DOSAGE AND ADMINISTRATION The full FDA-approved product insert is available at http://www.merial. Care must be taken to administer the proper dose deep into epaxial us/SiteCollectionDocuments/Immiticide_PI_8.5x11_version.pdf. Consult muscles ONLY (see boxed WARNING). Accurately weigh the dog and your veterinarian for further information. For technical assistance, calculate the volume to be injected based on the dose of 2.5 mg/kg (1.1 to request a Safety Data Sheet or to report suspected adverse events, mg/lb). This is equivalent to 0.1 mL/kg (0.045 mL/lb). See full product call 1-888-637-4251. For additional information about adverse event insert for dosing table. Use a 23 gauge 1 inch needle for dogs equal to or reporting for animal drugs, contact FDA at 1-888-FDA-VETS, or http:// less than 10 kg (22 lb) in weight. Use a 22 gauge 1 ½ inch needle for dogs www.fda.gov/AnimalVeterinary. greater than 10 kg (22 lb). Use alternating sides with each administration NADA 141-042 Marketed by Merial, Inc. and avoid injecting at the same lumbar location. ADVERTISERS INDEX

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May 2019 cliniciansbrief.com 71 QUIZ CORNER

QUIZ MANAGEMENT TREE page 11 1 NSAIDs are acceptable to use in patients with nonvenomous snake bites. YOURSELF A. True on this issue’s B. False features TOP 5 page 22 2 When viewed cytologically, small lymphocytes comprise Quiz Corner is approximately how much of a normal lymphocyte? offered by the A. 50% to 60% publisher for entertainment B. 70% to 80% purposes only C. 85% to 90% and does not apply toward CE D. 100% credit. Questions are provided by editorial staff and CASE IN POINT page 29 are not subject to Which of the following might be an appropriate recommendation peer review. 3 for a dog with suspected dilated cardiomyopathy? A. Obtaining a complete dietary history B. Taurine supplementation C. Echocardiographic examination D. All of the above

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IMPORTANT SAFETY INFORMATION: IMMITICIDE should not be used in dogs with very severe (Class 4) heartworm disease. IMMITICIDE should be administered by deep intramuscular injection in the lumbar (epaxial) muscles (L3–L5) only. Do not use in any other muscle group. Do not use intravenously. Care should be taken to avoid superﬁ cial injection or leakage. Serious adverse reactions may occur in any dog with heartworm disease due to the killing of heartworms in the pulmonary arteries. Reactions may include thromboembolism, dyspnea, coughing, depression, right side heart failure, and death. Dogs should be cage rested following treatment due to possible thromboembolic disease. Post-injection site reactions (eg, pain, swelling) were the most commonly reported adverse events. See full prescribing information for dosing and administration directions prior to each use of IMMITICIDE. For more information, please see full prescribing information.

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Expert Views from a Roundtable on Endocrine Disease

ABBREVIATIONS

ACTH Adrenocorticotropic hormone ALP Alkaline phosphatase Diagnosing Canine ALT Alanine transaminase HAC Hyperadrenocorticism LDDST Low-dose dexamethasone Hyperadrenocorticism suppression test PD Polydipsia PDH Pituitary-dependent hyperadrenocorticism PU Polyuria The first step in managing canine hyperadrenocorticism (HAC) is UCCR Urine cortisol:creatinine ratio to accurately diagnose patients. Given the non-specific clinical UPC Urine protein:creatinine ratio UTI Urinary tract infection signs, even defining which dogs should undergo endocrine testing can be problematic. Many dogs that should not be considered candidates are tested, whereas others are missed. Then the con- PARTICIPANTS Patty Lathan, VMD, MS, DACVIM sideration turns to which tests should be employed and why. Test (Small Animal) Associate Professor, Small Animal selection must be communicated to clients so they are open to Internal Medicine the idea of conducting what may be multiple tests. This discus- Mississippi State University Christopher Byers, DVM, DACVECC, sion will help clarify the diagnostic process and the criteria that CVJ, DACVIM (Small Animal) come into play as well as the way in which veterinarians portray CriticalCareDVM.com Brett Wasik, DVM, DACVIM (SAIM) the salient points to clients. Internal Medicine & Endocrinology Consultant Veterinary Information Network Internal Medicine Consultant Antech Diagnostics Dr. Zimmerman: How often do and modified water deprivation tests dogs elude a veterinarian’s consid- without thinking of the more common eration of HAC and instead come to tests. If you think you’ve got central MODERATOR you for other suspected conditions? diabetes insipidus, think again—and Nancy Zimmerman, DVM then think again a third time. Dr. Lathan: Approximately half my patients fall into this category. A dog came Dr. Lathan: I agree. 25% of presenta- in last week for a cardiac workup because tions of HAC fall outside the classic of excessive panting. We determined the description; a different presentation dog has HAC. of HAC is more common than diabetes insipidus. Dr. Byers: In dogs presenting for polydipsia/polyuria (PU/PD), HAC for Dr. Wasik: Another factor is that it’s some reason falls off the differential sometimes hard to motivate clients list. Sometimes clinicians jump to because they perceive increased steps such as desmopressin trials urination/drinking as normal in older

Clinician’s Forum 1 I do not recommend elective procedures requiring anesthesia for patients with HAC. I certainly do not recommend anesthesia for an untreated Cushingoid patient. —Dr. Byers

dogs. Or they are actually happy that history taking or the physical exam. the dog eats excessively because if he I don’t find a lot of polyphagia. With PU eats well then he’s got to be feeling well. or panting as the presenting complaint, when you roll the dog over, you might see If a dog spends the majority of time thin skin and obvious abdominal veins. outside or has a doggy door, the owners Calcinosis cutis, alopecia and other may not perceive PU/PD. So your first dermatologic lesions, and recurrent tip-off might be the ALP. infections may also be discovered. I look for 2 of these. Then I run chemistry and Dr. Zimmerman: How many dogs CBC. At that point I might want to conduct that you eventually diagnose with some sort of screening test. Cushing’s have been presented for something other than endocrine Dr. Byers: For me, it’s panting. Our disease (surgery, cardiology)? referrals may also have some type of advanced recurrent bacterial urinary Dr. Lathan: About 50%. Half of the cases tract infection or bacterial pyoderma. come in for a Cushing’s workup or for a workup of PU/PD, and the other half come Dr. Lathan: Polyuria, polydipsia, and in for a cardiology workup or surgery or panting, and we see our share of urinary another service. tract infections (UTIs) as well. In particular some male dogs have had bacteriuria, Dr. Zimmerman: What are the which is really uncommon in a male. Then common obstacles to identifying in looking for other clinical signs, we ask potential patients? whether the dog still wants to go on walks or has gotten any weaker lately. Many Dr. Byers: We have to be upfront with people attribute decreased energy levels clients about the potential costs of and muscle wasting to aging, but screening diagnostics because there is Cushing’s can cause that as well. not a perfect test. We have to be similarly upfront about staging diagnostics and Another aspect we see is referrals from that diagnosis is just the first step. Step 2 dermatologists: dogs that are losing hair, is lifelong management, requiring daily especially dogs with calcinosis cutis. medication and specific follow-up Some of those patients, as well as those evaluations. coming in because the client has noticed the dog’s rock-hard skin, look like the Dr. Zimmerman: What set of picture of classic HAC. clinical signs prompts you to think HAC and which are the key Dr. Zimmerman: What are some indications that remove it as your consequences of clinical signs being first consideration? attributed to aging?

Dr. Wasik: Polyuria and panting. Dr. Byers: As a criticalist, I have run Whether hypothyroidism or HAC is being into serious, life-threatening complica- manifested, those clinical signs seem to tions when an untreated HAC patient is be the 2 that I deal with most. I usually anesthetized. They are hypercoagulable try to identify at least 2 indicators, but and at risk for thromboemboli and generally patients are presented with stroke-like events. I do not recommend one and then we find another through elective procedures requiring anesthesia

2 Canine Hyperadrenocorticism for patients with HAC. I certainly do not that way in the patient population I’ve recommend anesthesia for an untreated seen, but it is not a huge difference. It’s Cushingoid patient unless absolutely partly a numbers game. For instance, if necessary. My input on that question is a you see 20 Cushing’s patients per year– little bit different because I am seeing the odds are 3 of them will have adrenal patients die. tumors, but I’m sure at least 1 or 2 of them are going to be small dogs. Dr. Lathan: The life-threatening sequela that we see is pulmonary Dr. Zimmerman: When is a workup thromboembolism. But we treat a lot for HAC not indicated? An untreated patient can of dogs with HAC each year (30-50 cases), present with 2 extremes: so I am not in the same environment as Dr. Wasik: With any sort of unwell Dr. Byers. We probably see only 3 or 4 patient—and an inappetent patient is Absolutely nothing, because pulmonary thromboemboli per year, always a big red flag. Patients with the house has a doggy door and those are generally in dogs that increased ALP routinely get inappropri- have been undiagnosed. ate HAC workups. The other subset of and the dog can go outside patients is those whose appetite is off a whenever it wants and is Dr. Wasik: Infections occur over and bit, with an ALT of 800 to 1000 and an over again in bigger dogs with ruptured ALP increase. There are 1 or 2 cases a eating well, or a dog comes cruciate. We deal with hypertension and year where HAC patients do get that in for a ruptured cruciate or proteinuria long-term. So for me, an degree of ALT elevation. But for the recurrent infections, untreated patient can present with 2 most part, if it’s that high there is likely extremes: Absolutely nothing, because something else going on—whether it is hypertension, and/or the house has a doggy door and the dog concurrent hepatopathy or cholangitis. proteinuria. can go outside whenever it wants and is If the ALT is, say, above 500, I am not in a eating well, or a dog comes in for a big rush to do an LDDST just because of —Dr. Wasik ruptured cruciate or recurrent infections, the concurrent ALP increase. Almost all hypertension, and/or proteinuria. these dogs have ALP increases, which I think initially prompts thinking about Dr. Zimmerman: How long do HAC. But if the dog is not eating, doesn’t you think affected dogs have have 2 of the classic signs, or has ALT of had clinical signs before being >500-600, we should apply the brakes to presented? considering screening tests for HAC.

Dr. Lathan: It’s a huge range. Some Dr. Byers: Thankfully, HAC is rarely a cases might have had signs for 3 or 4 life-threatening issue. So put that on years; the owner will tell you that their the back burner, and let’s work up the dog has always had PU/PD. In others, issues that are raising red flags. If a the signs have started pretty suddenly, dog is vomiting and has diarrhea and say a month ago. anorexia or hyporexia, it may very well have HAC but something else is causing Dr. Byers: My experience is very similar, those clinical signs. Let’s figure that out, but if I had to put an average on it, I would address it, get them feeling well for a say the clinical signs have been present while. Then if HAC signs persist, maybe for 3 to 6 months. it’s time to move on through a diagnostic process. Dr. Zimmerman: I’ve heard the generalization that big dogs tend to Dr. Wasik: Obvious anemia is another have more adrenal-based disease. big red flag for me. And when the Is that your experience? hematocrit is 32% to 33%, think again.

Dr. Lathan: We see a lot more small Dr. Lathan: If a patient has any dogs that have Cushing’s than big dogs, gastrointestinal signs, as HAC is not a and of the dogs that have adrenal direct cause of such signs. Also, if you tumors, more of them are small dogs, begin testing for HAC when a dog has but that’s probably because there are such signs, which are stressful, cortisol more small dogs with Cushing’s. There can thus be increased, causing a false was a study that looked at big dogs and positive test. I recommend holding off found they were more likely than small on doing diagnostics in these animals dogs to have adrenal tumors. I could because I don’t even know how to agree that it might be slightly skewed interpret the results.

Clinician’s Forum 3 For general practitioners who have an ability to either get the proper tubes for an endogenous ACTH or send the sample in dry ice, an ACTH test might be easier for them than ultrasound. —Dr. Lathan

Dr. Zimmerman: How long do you region, the classic patient with a macro- typically wait after you have the adenoma will react. It isn’t definitive for other condition under control to macroadenoma, but it does indicate start addressing the HAC increased intracranial pressure. possibility? Dr. Zimmerman: None of you has Dr. Lathan: I’d say 2 to 4 weeks. mentioned urine cortisol:creatinine ratio (UCCR). Isn’t it a very good Dr. Byers: I tell primary care partners test in terms of ruling out the that I want their patient to be feeling disease? good—with the exclusion of consistent clinical signs of Cushing’s disease—for Dr. Byers: In a patient presented for at least 2 weeks. PU/PD, after I’ve done my exam and have thoroughly reviewed medical records Dr. Wasik: It’s more related to the clinical from the primary care partner and have picture. I want to see the anemia or other chatted with the family, I will pursue a aberrant sign resolved, but the liver UCCR if I have little suspicion of HAC. But enzymes are never going to get dramati- when I am simply proceeding through a cally better. So, if the dog is feeling good, logical PU/PD workup and looking through bouncing around the room, and is still the list of causes of secondary nephrogen- PU/PD for at least 2 to 4 weeks, I would ic diabetes insipidus, I don’t use a UCCR. say, “Yes, if this were my dog I’d be looking for HAC.” Dr. Lathan: I would never run a UCCR in a dog in which I had considerable Dr. Lathan: We haven’t talked about suspicion of HAC because it is not a macroadenomas. Dogs come in for specific enough test. anorexia and it turns out that we don’t find anything on a regular workup other Dr. Byers: I more often recommend a than evidence of HAC and just have a UCCR to a primary care provider with suspicion of macroadenoma based on whom I am doing a telephone consulta- clinical signs. Then we end up doing tion rather than perform it myself. Often imaging of the brain. In those cases, the a doctor will call with a case that isn’t dog having clinical signs of HAC actually raising a lot of red flags for HAC, but for helps in our diagnosis of macroadenoma. which technically HAC is on the list of secondary nephrogenic diabetes insipidus Dr. Wasik: History is critical in those causes. I tell them to run the UCCR. If it’s cases because they won’t be the typical normal, you can feel comfortable moving presentation of Cushing’s. on to other things.

Dr. Byers: One thing that has helped Dr. Zimmerman: Why do you do an me proceed to advanced imaging more LDDST as the first test rather than rapidly in suspected macroadenoma is an ACTH stimulation test? Is there focusing on a complete neurologic exam, some sort of rule about when you including what I call a “calvarial pressure” do a suppression test rather than a test. Patients with macroadenomas stimulation test? typically have some degree of intracranial pressure elevation, so if you apply a little Dr. Lathan: The oversecretion diseases pressure bilaterally on the temporal should always be tested with suppression

4 Canine Hyperadrenocorticism tests. We are trying to determine whether send a plasma sample in a plastic the hypothalamic-pituitary-adrenal axis purple-top tube on dry ice, an endoge- is intact. The test tells us whether the nous ACTH test might be easier than pituitary, and subsequently the adrenal ultrasound. It’s very rare that getting a gland, responds to dexamethasone’s diagnosis of HAC is an urgent matter, message to stop secreting ACTH and so they can wait a week for the results. cortisol. Dr. Byers: That’s an important point. A full 65% of pituitary-dependent Cushing’s is not an urgency. Take your hyperadrenocorticism (PDH) will respond time and make sure you are comfortable to the suppression test in either the 4- or with the diagnosis. 8-hour form, but it’s critical that veterinarians understand that lack of suppression Dr. Lathan: If you have a high index does not mean it’s an adrenal tumor. If of suspicion and finances are not an there is not suppression to a value <1.4 issue, then I would collect blood for an at 4 hours, then some vets think the dog endogenous ACTH concentration before absolutely has an adrenal tumor. We an LDDST or ACTH stimulation test, as know that 35% of dogs with PDH do not both dexamethasone and ACTH can alter exhibit any suppression during the LDDST. the test results. Thus, more dogs that don’t suppress during the test have PDH than adrenal- Dr. Wasik: I probably use ultrasound dependent disease. more so than an endogenous ACTH concentration; I trust what I see on the Cushing’s is not an urgency. Dr. Zimmerman: Is there any value ultrasound more than an endogenous Take your time and make to an ACTH stimulation test? ACTH. sure you are comfortable Dr. Lathan: There is. The reason that Dr. Zimmerman: How often do you with the diagnosis. many clinicians at vet schools run ACTH see Cushingoid dogs that after the stimulation tests is completely logistical. diagnostic process turn out to be —Dr. Byers Clients may be driving 2 or more hours iatrogenic? and they want to go back the same day. So, we’ll do an ACTH stimulation after Dr. Lathan: It’s really uncommon for explaining that we have a 70% to 80% me. Most referring veterinarians have chance of the test being positive if the been able to weed those out. There are dog has HAC. I make sure they understand occasional dogs that have been receiving that I think an LDDST is better, but it takes ear drops that we don’t know about. I 8 hours. think it’s prudent to specifically ask, “Are you putting anything into your dog’s If I do an ACTH stimulation test and I ears?” Because for some reason, some have confirmation of HAC, I don’t follow clients do not think that otic products are with LDDST. I believe the ACTH stimula- actually medication. tion test is a pretty specific test. The ACTH stimulation test is a pretty specific test; it Dr. Zimmerman: Given that just isn’t as sensitive as the LDDST and history and clinical signs are doesn’t differentiate. If it confirms the consistent with HAC, the dog diagnosis of HAC, I usually follow up with is eating well and has a normal an abdominal ultrasound or endogenous activity level and blood glucose, ACTH concentration for differentiation. and LDDST is positive, you can confirm HAC and start conversa- Dr. Wasik: It depends on how quickly tions about treatment? you can get an endogenous ACTH. Are you sending it to a lab where it is going to sit Dr. Wasik: Establishing what is a positive for 48 to 72 hours? Are you overnighting it result is important. Practitioners think so it’s run the next day? Or are you at a HAC is indicated if 50% suppression is university where you can walk it to the achieved at 4 hours. But that really lab? That plays a factor in doing an doesn’t mean anything unless you have endogenous ACTH versus not. escape at 8 hours.

Dr. Lathan: For general practitioners My first step in examining an LDDST is who have an ability to either get the always to look at the 8-hour result first. special sample tubes from their lab or If it is above the reference range and the

Clinician’s Forum 5 Cost is a big factor, so I like to have an estimate for each phase of management. That part of the educational discussion takes at least 45 minutes to an hour. —Dr. Wasik

patient has appropriate physical exam- dog with HAC has 1+ proteinuria, I usually ination changes and lab results, I can at don’t worry too much. If it is 2+ or more, least be comfortable it has HAC. Then I I check a UPC. UPC should also be look at the 4-hour result. If there isn’t any interpreted in combination with blood suppression, then I calculate 50% of my pressure, partially because an ACE baseline. If the 4- or 8-hour value is below inhibitor can treat both. that calculation, I have differentiation with respect to PDH. So, it’s a 3-step process. Dr. Zimmerman: How would you recommend conducting a conversa- Dr. Lathan: That last part is really tion so that clients understand the important. Most veterinarians are aware disease and do not become morbid- that a value <1.4 at 4 hours is consistent ly scared but appreciate that there with PDH. A large portion forget, however, is suffering? that if the 4- or 8-hour sample is less than half of baseline, then that is also Dr. Byers: Doctor and owner should consistent with PDH. have an educational conversation. It is also critical to make sure that clients Dr. Zimmerman: When you are know they can contact you or your team suspicious of HAC, do you always with questions after they leave. A client measure blood pressure and urine hearing that the door is open to asking protein:creatinine (UPC) ratio? questions later really sets a foundation for respecting your medical decisions, Dr. Lathan: Yes, we typically check heeding them, and being a good partner blood pressure, but I don’t think that is in care. absolutely necessary unless a patient has some clinical sign of hypertension. Unless I was taught that instead of saying, the patient has a value of 180 mm Hg or “Does that make sense?” to ask the more, I will not treat hypertension unless client, “Did I explain that okay?” The the dog has clinical signs of hypertension. rationale behind that nuance is that a lot of pet parents do not feel comfortable Dr. Byers: I’m more aggressive. I do not admitting when they don’t understand. like systolic blood pressure >150 mm Hg So when you ask them, “Does that make during the hospital period. That does not sense?” they are going to say yes, mean I will initiate therapy with one value absolutely, when they really didn’t get it. over 150 mm Hg. If I document systolic blood pressure consistently >150 mm Hg, Dr. Lathan: It can be easy enough just to I will treat it. Some literature has shown start out with an explanation that most of that Cushingoid hypertensive patients did the dogs with Cushing’s have a tiny little not have their hypertension resolved. tumor in the brain. The tumor doesn’t They could not be weaned from their cause any problems in the brain, but it hypertension medication through causes the signs of Cushing’s because it adequate control of their hypercorti- affects the adrenal glands. solemia. That is my justification for being aggressive with screening, monitoring, Dr. Byers: Actually, I don’t use the word and therapy for any blood pressure >150 tumor. I say space-occupying lesion and mm Hg systolic. then I draw. I highly recommend drawing Also, the average animal owner has heard Dr. Lathan: In terms of UPC ratio, if a the term hormone. They have a vague

6 Canine Hyperadrenocorticism understanding of hormones. So I say see the point of running the diagnostics. that part of the brain is inappropriately You have to decide whether to work to secreting a hormone that travels in the differentiate the condition. Is it worth bloodstream to affect the adrenal glands. spending $300-$700 when you know that I try to use familiar terms. Anatomically, the owner is concerned about the cost? I’d I use an analogy of a peanut M&M. The rather spend that $300-$600 on trilostane. medulla is the peanut and the cortex is the chocolate coating. I tell them the Dr. Zimmerman: A recent study1 problem is in the chocolate. showed that approximately 80% of dogs with suspected HAC never had Dr. Zimmerman: How do you differentiation accomplished at the convey the value of the expense of GP level. How often do you differ- management? entiate adrenal versus pituitary disease? Dr. Byers: I start at the endpoint—that there is a survival benefit. Essentially you Dr. Byers: I would say about 50%, but I explain, “Good job for coming in. You am infrequently able to check every box recognized some big red flags. Here’s that I want for complete differentiation what I think it is. We are going to do our (endogenous ACTH, ultrasound). I am best to prove that. If it’s proven, we are usually able to get the ultrasound, but going to treat it and here is why we treat they hold off on another blood test, which it.” That’s the initial cursory explanation; is fine. What is important is for every pet then you dive deeper into how we make parent to hear what can be done and why I was taught that instead of the diagnosis and how we treat it. we recommend doing it. saying, “Does that make Dr. Wasik: Clients do not care about Dr. Wasik: We are definitely skewed at sense?” to ask the client, sensitivity/specificity of each individual Davis. A lot more people do testing. I “Did I explain that okay?” test; they just want to know what to do. usually do a combination of an LDDST Cost is a big factor, so I like to have an and ultrasound if necessary. I don’t do a The rationale behind that estimate for each phase of management: lot of endogenous ACTH tests myself, nuance is that a lot of pet This is what the first couple of months of except in certain circumstances. If surgery treatment and monitoring will look like. is a no-go, it doesn’t matter whether I parents do not feel Then afterward every 3 to 4 months is prove there is a metastatic tumor. If I can comfortable admitting when going to look like this. That part of the at least get them to do medical therapy, educational discussion takes at least 45 we will start with the LDDST and then we they don’t understand. minutes to an hour. can resort to the ultrasound as needed. —Dr. Byers

Dr. Byers: That is a big take-away for our Dr. Lathan: We probably differentiate primary care partners: That you just can’t 80% to the point that I am certain they do meaningful client education about are either adrenal or PDH. That rate may Cushing’s disease in 10 to 15 or even 30 be due to the fact that we have relatively minutes. inexpensive ultrasound ($225). Between the ultrasound and LDDST, I can differenti- Dr. Lathan: I start off by establishing ate 90%. which clinical signs are actually bothering the owner. Why did they bring the dog in? LDDST is the way to go. I wish veterinari- And I say that with treatment these signs ans could get clients to do that before will reduce or stop. they come in to see us.

Dr. Zimmerman: Any other tips on Dr. Zimmerman: How do you then how to deal with reluctance to discuss the risk versus the benefit enter into diagnosis and treat- of treatment? ment? Are there specific ways that you address the cost? Dr. Lathan: We tell clients the best way to minimize the risk is for them to pay Dr. Lathan: In the beginning, especially attention to the patient’s signs, to keep a for patients with milder clinical signs, I ask journal. clients whether they have the finances to treat. If they can’t even scrape together Dr. Byers: They need to feel that we the money to do an LDDST and it’s a are a team, that they are not going to classic presentation of HAC, I often don’t be left alone to face this. You need to be

Clinician’s Forum 7 We talk about the medicine, but let’s be honest; medicine isn’t the only thing at play here. It’s that human-animal bond. —Dr. Byers

up front with them about how the drug Dr. Byers: In a non-emergency scenario, works and the potential risks, including you should be sending your samples to that some patients have died during your preferred reference laboratory. treatment. That’s just a reality. I don’t emphasize it, but I say it because I feel Dr. Lathan: There are more results in the when owners hear you say even the gray zone with an ACTH stim when a worst things about any drug, they compounded version of ACTH is used understand that you are telling them versus the FDA-approved version. everything, not glossing over the risks. We talk about the medicine, but let’s be Also, I would stress that I don’t do honest; medicine isn’t the only thing at diagnostics for Cushing’s unless the play here. It’s that human-animal bond. patient has clinical signs and the owner Giving a pet medicine once or twice a day has at least some intention to treat. For will sometimes negatively affect the example, I don’t want to do diagnostics CLIENT RESOURCE owner’s bond with the pet. It is some- for Cushing’s in a dog with an increased thing for them to consider before testing ALP but no clinical signs, as I would not A new client handout on Cushing’s or treatment is started. treat that patient for Cushing’s. disease can be accessed at Dr. Wasik: This is a good place for a cliniciansbrief.com/HAC-handout-2019 Dr. Zimmerman: What additional strong technical support team. If you resources do you think GPs can find see many HAC patients or have a heavy useful in the diagnostic phase? endocrinology caseload, a very compe- tent technical staff can stress how Dr. Byers: Tell them to ask questions. We important the role of the client is in both internists recognize referral is not always medicating and monitoring their pets’ an option. That doesn’t mean we can’t try response to therapy and communicating to help. You’re probably not going to get a that with your team. call within an hour, but we’ll be able to touch base in fewer than 24. In general, Dr. Lathan: It is also ideal to have don’t be afraid to reach out. We’re human; them call the technician back every day we just want to help the patient. for the first few days after they start on the medication. Maybe it’s just a 30 Dr. Lathan: I think one thing that we second phone call. “Hey, how’s Fluffy didn’t talk about is sending home a doing? Is she taking the medication well? client information sheet. Provide client Are you able to get it into her?” That helps information sheets so they can read them establish the line of communication. later because they probably only remem- ber 10% of what you told them. Dr. Zimmerman: When you are having a consultation with the Reference general practitioner, what are some 1. O’Neill DG, Scudder C, Faire JM, et al. tips or caveats that you offer? Epidemiology of hyperadrenocorticism among 210,824 dogs attending primary-care veterinary practices in the UK from 2009 to Dr. Lathan: You can use dexamethasone 2014. JSAP. 2016:57(7):365-373. doi: 10.111/ or dex-SP for an LDDST, but the concen- jsap.12523 Copyright 2019 tration of dex-SP is 4 mg/mL, 1 mg/mL of Educational Concepts, LLC, which is sodium phosphate. So you need dba Brief Media to divide by 3, not 4.

8 Canine Hyperadrenocorticism