A Matter of Opinion CONTINUED

One of the pri-mary goals of theOne Health Com-mission is toadvance theunderstanding,prevention, andtreatment ofzoonotic disease.

THE ROOTS OF COLLABORATIONThe concept of One Health was a central theme in the earlydays of our profession. Cornell’s first veterinary dean, James Law, pro-moted the notion in an 1878 address to the Pennsylvania Department of Agriculture3:

“Now that veterinary medicine has been established on a scientific basis, the time has come whenthe bonds that unite the students and practitioners of human and veterinary medicine should beknit more closely, and the two branches be brought into more intimate relationship. Both branchesof medicine suffer from separation…. Each is necessary to the rapid progress and highest advance-ment of the other.”

In the late 19th century, the fields of veterinary and human medicine were intertwined. For example,some of the great physicians and biomedical scientists, such as William Osler and Theobald Smith,were closely associated with veterinary medicine’s greatest leaders ( James Law, Daniel Salmon, andAlexandre Liautard). In fact, it was not uncommon for deans and some faculty of veterinary collegesto be physicians or to hold both MD and DVM degrees.1

the profession’s history, some of the approxi-mately 35 city-located veterinary colleges—including those at Harvard University, New YorkUniversity, and George Washington University—were associated with major medical schools. Bythe 1920s, however, all except one of our veteri-nary colleges (the exception being University ofPennsylvania, which was an outgrowth of themedical school) were located in rural communi-ties such as Pullman, Washington, and Ithaca,New York, or in small cities such as Columbus,Ohio. The land grant’s agricultural priority gov-erned veterinary college curricula and entrancerequirements and, unfortunately, narrowed theveterinary community’s understanding of OneMedicine to the (albeit important) priority forpublic health.1

Meanwhile, human medicine thrived in thepopulation centers of the country and physi-cians devoted their energy to advancing medicaldiagnoses and treatments and developing clini-cal specialties that enhanced individual patientcare. Ironically, starting as far back as the late1800s, physicians also became experts in caninephysiology, pathology, and surgery. They devel-oped important veterinary medical and surgicaltechniques decades before veterinarians did,even those who were working and teaching inveterinary colleges. The medical professionused dogs as correlates for human medicine,

and most of this work was done in the absenceof veterinarians.2

Instead, veterinarians continued to promotehuman health by ensuring the safety of the foodsupply, preventing major zoonotic scourges suchas salmonellosis and tuberculosis, and controllingthe dreaded scourge of rabies. Unfortunately,there was less and less contact between physiciansand veterinarians, with each working in theirrespective spheres.

ZOONOTIC DISEASE MAKES ACOMEBACKBy the mid-20th century, veterinary prophetsadvocated for a resurgence of One Health. Amongthem were Dr. James H. Steele, the father of vet-erinary public health, and Dr. Calvin W. Schwabe,who developed the parallel field of veterinary epi-demiology. Zoonotic diseases once again took cen-ter stage, and the comparative medical educationof veterinarians enabled many important clinicaland research advances in human health. Dr. TraceyMcNamara’s groundbreaking work on West Nilevirus at the Bronx Zoo in 1999 helped solidify theveterinarian’s role in the diagnosis, treatment, andprevention of zoonotic disease.

In 2006 and 2007, Dr. Roger Mahr used his posi-tion as AVMA president to advocate for a 21stcentury movement in One Health. He and col-leagues in veterinary medicine and other healthprofessions have forged leadership alliances from

42.......................................................................................................................................................................NAVC Clinician’s Brief / July 2011 / A Matter of Opinion

Advancing One Health:Practical Tips for Veterinarians

Veterinarians can take a number of practical steps to promote One Health and forge collaborative bonds with theircounterparts in human medicine:

education, research, government, and industry topromote comparative medicine in advancinghuman, animal, and ecosystem health. A perma-nent administrative home for the One HealthCommission has recently been created at IowaState University.

THE GOALS OF ONE HEALTHPromoting Public HealthOne of the primary goals of the One HealthCommission is to advance the understanding,

prevention, and treatment of zoonotic disease.During the past few years, the increasing number,scope, and virulence of zoonotic pathogens; themore rapid speed with which these pathogenstravel around the world; and the growingimmunocompromised human population havecompelled us to keep this issue at the forefrontof the One Health movement.

A Matter of Opinion / NAVC Clinician’s Brief / July 2011.......................................................................................................................................................................43

� Encourage prospective veterinary students to attendundergraduate colleges and major in biologicalsciences in conjunction with premedical students inorder to form lifelong personal and professionalbonds that will facilitate mutual understanding ofthe health professions.

� Encourage veterinary colleges to accept MCAT(medical college admission test) scores as well asGRE (general record examination) scores toaccommodate students who may wish to considereither field.

� Encourage exchange programs between veterinaryand medical students by inviting medical studentsor family practice residents to visit your practice toobserve the human–animal relationships thatveterinarians encounter in clinical practice.

� Become informed about and engaged with humanhealth care needs and issues, including those withno direct relevance to pets or other animals.

� Encourage physicians (as well as insurance

companies and politicians) to understand andsupport the positive impact that pets play inenhancing human health.

� Become active with local and regional departmentsof health.

� Encourage and support innovative roles forappropriately selected animals in settings in whichanimals are known to positively enhance the livingexperience, such as retirement and assisted-livinghomes, hospitals and hospice care facilities,selected child care facilities, and prisons anddetention centers, among others.

� Encourage responsible ownership of pets tominimize challenges such as noise (barking),indiscriminant soiling, property and home damage,and aggression/biting.

� Encourage collaborative work between MDsand DVMs in the management of any immuno-compromised person with pets.

CONT INUES

with pets. This is a field in which veterinariansundoubtedly can have a major impact on humanhealth. If these benefits can be proven to be tan-gible and measurable, we have the potential todecrease the cost of human health care and toimprove the quality of life for both people andanimals. The term zooeyia (the positive impact ofpets on human health) represents a cogent way toexpress and build upon this important founda-tional concept.4

BACK TO THE FUTUREThe 21st century can and should become a “Backto the Future” moment for the One Healthmovement. A number of valuable resources areavailable for veterinarians to better understandOne Health (see One Health Resources), andthere are a host of constructive ways in whichveterinarians can join the movement (seeAdvancing One Health: Practical Tips for Vet-erinarians, page 43). How marvelous would it beto celebrate the profession’s 150th anniversary in2013 with the entire veterinary community com-mitting to a broader understanding of OneHealth for the betterment of all species?

A Matter of Opinion CONTINUED

44.......................................................................................................................................................................NAVC Clinician’s Brief / July 2011 / A Matter of Opinion

A growing bodyof research iscontinuallydocumentingimprovement inthe physical,social, andmental healthof people whoshare theirhomes and envi-ronments withpets.

ONE HEALTH RESOURCESThe following organizations offerinformative resources to provide abroader understanding of the conceptand goals of One Health:

American Veterinary MedicalAssociation:

www.avma.org/onehealthCenters for Disease Control and Prevention:

www.cdc.gov/onehealthOne Health Commission:

onehealthcommission.orgOne Health Initiative:

onehealthinitiative.com

See Aids & Resources,back page, for references& suggested reading.

Integrating Biomedical ResearchA second primary intention of One Health is toexploit the strong correlation between human andanimal health issues through biomedical researchin such areas as oncology, nutrition, obesity, chem-ical and environmental risks, and aging. The fieldof comparative genomics, introduced barely adecade ago, provides us with the scientific tools tostudy diseases and conditions that have a geneticor inherited component, including certain cancers,endocrine and joint diseases, and even somedegenerative and behavioral conditions. Becausehuman and animal genomes have so much incommon and because correlates for some humanconditions are manifested in dogs and other ani-mals, more rapid research advances can be realizedthrough strong collaborative ties between veteri-narians and physicians.

Exploiting “Zooeyia”The importance of pets to human health is wellestablished and cannot be overlooked whenconsidering One Health. A growing body ofresearch is continually documenting improve-ment in the physical, social, and mental health ofpeople who share their homes and environments

CASE SCENARIOIn February, Jocko presents for a routine semian-nual visit to his veterinarian in Sayre, Pennsylva-nia, a small town located in the north-centralpart of the state. The owner, Mrs. Jacobs, is awidow who lives by herself in Lehigh Towers, aretirement apartment complex maintained underthe Sayre community’s housing authority. Eachtenant is allowed to have a single pet cat or smalldog, but pets are forbidden access to the facility’sgrounds, so Jocko is truly an indoor cat.

When it comes to flea control, Mrs. Jacobs ishappy enough with how Jocko has been faringover the past 6 months and would like to staythe course on monthly Program (lufenuron,program.novartis.us). During this visit, she needsthe veterinarian to complete the required annualcertification that Jocko is flea-free.

Unfortunately, Jocko is anything but flea-free.Thus the veterinarian is left with a conundrum:What can be done to help Mrs. Jacobs keep Jockoas well as protect the other elderly folks living inLehigh Towers?

Wha t ’s t h e Take Home? PA R A S I TO L O G Y

What’s the Take-Home? / NAVC Clinician’s Brief / July 2011 ................................................................................................................................................................47

Dwight D. Bowman, MS, PhDCornell University

Peer Reviewed

Jocko, a 6-year-old neutered male

indoor-only cat, suddenly developed

a severe flea problem.

ASK YOURSELF…

What actions can be taken so the veterinarian cansign the required flea-free certification form—andJocko can return to his home and previous flea-freestatus?A. Switch Jocko to an oral or topical adulticide.B. Switch to injectable Program because you suspect

Mrs. Jacobs has not been religious in givingmonthly Program in Jocko’s food.

C. Give Mrs. Jacobs 7 days of Capstar (nitenpyram,capstar.novartis.us), tell her to continue withProgram, and send her home.

D. Give Mrs. Jacobs 7 days of Capstar and suggest ahouse visit by your veterinary technician who hasexpertise in resolving flea problems.

E. Give Mrs. Jacobs 7 days of Capstar and a fleabomb to treat the premises.

F. Give Mrs. Jacobs 7 days of Capstar and switch thecat to Revolution (selamectin, revolutionpet.com)along with applying Frontline Plus (fipronil + (S)-methoprene, frontline.us.merial.com) eachmonth.

G. Switch Jocko to Advantage (imidacloprid,bayerdvm.com) and use an additional carpettreatment.

H. Stay the course and inform Mrs. Jacobs that sheneeds to rent a carpet steamer.

Flea Management:An Integrated Approach

CONT INUES

To learn more

about flea species and the infectiouspathogens they can harbor, download alist at cliniciansbrief.com.

In fact, Pulex irritans is aspecies with a diversified hostspectrum, including bothdomesticated and wildmammals and birds—dogs,wild canids, pet cats, wildfelids, pigs, monkeys incaptivity, wild rodents, free-tailed bats, to name just afew, and of course people.

One of the more abundant fleaspecies is Ctenocephalides felis,which is the cat flea. Its primaryhost is domestic cats, but itis also a major player in fleainfestation of dogs. Although catfleas will bite humans, they are nota sustainable host. Therefore,survival relies on infestation ofother mammals.

Although Ctenocephalides canisprimarily lives off the blood ofdogs, it also feeds on domesticcats and sometimes biteshumans. The dog flea can livefor months in carpets, couches,bedding, and other placeswithout needing a blood meal.However, the female must havea blood meal before it canproduce eggs, which it lays onthe host’s fur.

Did You Know?One of the most common flea species seen inhouseholds today isn’t the cat flea or the dog flea—it’s the human flea.

By giving 1 Capstar tablet to Jocko during thisvisit and having Mrs. Jacobs give him 1 tabletdaily for 6 days (total of 7 days of Capstar treat-ment), you should be able to sign the documentwith a clear con-science2—but onlyif there is properfollow-up.

Managing this fleaproblem is going torequire veterinarystaff intervention—as well as assistance from the building’s adminis-trator. Jocko has obviously found himself in asituation in which fleas are breeding around himand have now sneaked into his environment.Thus a member of your team needs to use his orher knowledge of flea biology to figure out thesource for the large numbers of fleas moving intoJocko’s apartment.

Wha t ’s t h e Take -Home? CONT INUED

CORRECT ANSWERD. Give Mrs. Jacobs 7 days of Capstarand suggest a house visit by your vet-erinary technician who has expertisein resolving flea problems.

WEIGHING YOUR OPTIONSFrom the Case Scenario, it should be clear thatthis very likely is not a simple case of productfailure. Although that is always a possibility, Mrs.Jacobs receives her product from you, and youhave had no complaints from others about its use.Yes, someone always must be the first to com-plain when problems arise, but in this case, Jockois probably suffering from a shared affliction.

Obviously, fleas must have slipped into the Tow-ers and taken up residence, so a search for theoffending party or parties needs to be initiated.1

Jocko is likely serving as a sentinel, as the fleacontrol product being used on him has no adulti-cidal effect.

Ctenocephalides feliscaptured in an apartment(male left, female right)

What’s the Take-Home? / NAVC Clinician’s Brief / July 2011 ................................................................................................................................................................49

CONT INUES

THE SOURCE & SOLUTIONAlthough using various products with adulticidal,ovicidal, and larvicidal activities would likely pro-tect Jocko and Mrs. Jacobs from being botheredby fleas, the problem probably extends into thesurrounding apartments.3 Thus, the best meansof success in this scenario would be to send theclinic’s flea expert to the Towers to determine thesource of flea infestation. This can be challengingbecause of the number of individual apartmentsthat could be involved, but often the administra-tive staff in residence facilities is willing to workwith concerned, knowledgeable individuals inorder to prevent problems from getting out ofcontrol.

In this case, once the staff technician withexpertise in flea management visited the Towersthe problem was easily solved. The tenant in thenext apartment had taken his dog, which was not

on flea prevention, for a week-long visit to hisdaughter’s house. During that time, the fleas inthe neighbor’s apartment eclosed from theirpupal cases but had no host with the dog beinggone, so they started looking for a new bloodsource. The timing coincided with Jocko’s sched-uled wellness visit and the owner’s need to obtaina flea-free certification.

Source found. Problem solved.

Although reviewing all viable approaches to inte-grated flea management is beyond the scope ofthis article, a few options that can be consideredfor Jocko are outlined in Finding a Solution forJocko: Flea Control Strategies.

50 ................................................................................................................................................................NAVC Clinician’s Brief / July 2011 / What’s the Take-Home?

Wha t ’s t h e Take -Home? CONT INUED

See Aids & Resources,back page, for references& suggested reading.

Sometimesmanaging fleaproblemsrequires directintervention byveterinary staffwith expertise inflea biology.

FINDING A SOLUTION FOR JOCKO:FLEA CONTROL STRATEGIES

1. Continue flea prevention with Program for Jocko orperhaps for the dog that created the problem, Sentinel(milbemycin + lufenuron, sentinelpet.com), along withCapstar for both pets. The latter rapidly kills adultfleas, and lufenuron prevents fleas from developing.

2. Various adulticides contain built-in activities againsteggs, larvae, or both. For example, Revolution, Front-line Plus for Cats and Kittens, Advantage II (imida-cloprid + pyriproxyfen, bayerdvm.com), and Vectrafor Cats and Kittens (dinotefuran + pyriproxifen,summitvetpharm.com).3,4 These products have

excellent integrated pest control by targeting differentlife cycle stages.

3. Comfortis for Dogs (spinosad, comfortis4dogs.com)and Assurity for Cats (spinetoram, assurity4cats.com)are two products that were launched more recently forflea control.5,6 These products target adult fleas with aonce-a-month application, and in this scenario wherecats and dogs in the Towers never roam, these prod-ucts too would be likely to get this problem undercontrol and keep it away for an extended period.

Many scenarios can be played out to bringJocko’s flea problem under control. Followingare 3 options to consider when devising anintegrated flea control strategy.

Advantage = imidacloprid, Advantage II = imidacloprid + pyriproxyfen, Assurity for Cats = spinetoram, Capstar = nitenpyram, Comfortis for Dogs = spinosad,Frontline Plus = fipronil + (s)-methoprene, Program = lufenuron, Revolution = selamectin, Sentinel = milbemycin + lufenuron, Vectra for Cats and Kittens =dinotefuran + pyriproxyfen

Finding a Consensus onCanine CVHD

Canine chronic valvular heart disease (CVHD) is the most important

nonparasitic cardiovascular disease in veterinary medicine, but

controversy remains about the best treatment.

THE PLAYERSCanine CVHD, also known as endocardiosis,myxomatous valve degeneration, and mitralregurgitation (MR), affects approximately 85%of dogs 13 years of age or older and accounts for75% of heart disease in dogs.1 For such a sub-stantial disease, it may be surprising that therestill is controversy and general lack of agreementabout the appropriate medical management, bothbefore and after the onset of heart failure.

To this end, the American College of VeterinaryInternal Medicine’s (ACVIM) Board of Regentsrecently selected a group of European and Amer-ican board-certified cardiologists to present aformal consensus for the diagnosis and treatmentof CVHD.1 The 10 panel members representeddiverse points of view on cardiac therapeutics.

The consensus statements and recommendationsof the panel are not to be taken as “cutting edge”but rather as a sampling of the “collective wis-dom” that occurs when reasonable people reach acompromise after reviewing published data andtheir own experiences.

THE PROCESSBased on available evidence, the ACVIM paneldetermined whether the potential benefits of agiven treatment option clearly outweighed therisk for adverse events and if the financial impacton the patient and client would be justifiable.

How I Treat / NAVC Clinician’s Brief / July 2011 .....................................................................................................................................................................................53

Clarke Atkins, DVM, Diplomate ACVIM(Internal Medicine & Cardiology),

North Carolina State UniversityPeer Reviewed

CONT INUES

How I Tre a t C A R D I O L O G Y

THE PANELBruce Keene, DVM, MSc, Diplomate ACVIM, Panel ChairClarke Atkins, DVM, Diplomate ACVIM (Internal Medicine & Cardiology)John Bonagura, DVM, MS, Diplomate ACVIMStephen J. Ettinger, DVM, Diplomate ACVIM (Internal Medicine &

Cardiology)Philip R. Fox, DVM, MS, Diplomate ACVIM/ECVIM (Cardiology) & ACVECCVirginia Luis-Fuentes, VetMB, PhD, CertVR, DVC, MRCVS, Diplomate

ACVIM & ECVIMSonya G. Gordon, DVM, DVSc, Diplomate ACVIM (Cardiology)Jens Häggström, DVM, PhD, Diplomate ECVIM (Cardiology)Robert Hamlin, DVM, PhD, Diplomate ACVIMRebecca Stepien, DVM, Diplomate ACVIM

ACVIM = American College of Veterinary Internal Medicine, CVHD = chronic valvular heart disease

Consensus was defined as all 10 panelmembers agreeing to a particular recom-mendation, but we also revealed when amajority of the panelists agreed on a rec-ommendation even if the criteria forconsensus were not met.

HEALTH CARE SCHEMEAlthough a number of classificationschemes that grade cardiac disease indogs are already in place, we created anovel scheme modeled after one used bythe American Heart Association and theAmerican College of Cardiology. Oursystem avoids the inclusion of progres-sive exercise intolerance when gradingdisease severity and adds a category fordogs that show no clinical signs but areat risk for the disease (eg, cavalier KingCharles spaniels, dachshunds, miniatureand toy poodles).

In this article, I describe some of themore important consensus and majorityfindings from the panel, as well as offersome insights into how these findingscan translate into everyday patient carebased on my own practice.

Note: Not all consensus recommenda-tions would be appropriate for eachpatient. For example, it is unlikely that adog on pimobendan would also receivedobutamine.

How I Tre a t CONT INUED

ACVIM classi f icat ion� Patient at risk� No clinical signs

From the panel� No drug or dietary therapyrecommended at this stage

� Dogs used for breeding should beremoved from the breeding pro-gram if MR is present

For my pat ientsFor dogs with stage A CVHD, Imake the dog’s owner aware of theneed for annual examinations, whatmay lie ahead if the disease pro-gresses, and what an aggressivediagnostic and therapeutic approachmight entail. I also discuss what canbe done for a patient if the ownerhas financial constraints. I discussdiet and exercise and the role ofdietary restrictions as heart failureensues. I also give the owners aprognosis and inform them as tohow various predictable and unpre-dictable circumstances might alterthe general expectation.

54 .....................................................................................................................................................................................NAVC Clinician’s Brief / July 2011 / How I Treat

S T A G E A S T A G E B1ACVIM classi f icat ion� Murmur present� No cardiomegaly

From the panel� Consensus: No drug or dietarytherapy recommended at thisstage for dogs with hemodynam-ically insignificant MR, definedhere as radiographic or echocar-diographic evidence of a normalor equivocally enlarged leftatrium, left ventricle, or both, inaddition to normal left ventricu-lar systolic function, normal ver-tebral heart score on radiography,normal blood pressure, and nor-mal laboratory results

For my pat ientsI suggest to owners that the dogmay benefit in the long-term from adiet that is mildly to moderatelyrestricted in sodium content, whilethe dog’s appetite is presumably stillgood. I also suggest blood pressurecontrol—most likely with the addi-tion of amlodipine and an ACEinhibitor in the relatively unusualcircumstance in which systemichypertension accompanies CVHD.This is true at any stage of CVHD.

ACE = angiotensin-converting enzyme, ACVIM = AmericanCollege of Veterinary Internal Medicine, CVHD = chronic valvularheart disease, IMPROVE = invasive multicenter prospectiveveterinary evaluation of enalapril study, MR = mitral regurgitation,RAAS = renin–angiotensin–aldosterone system

S T A G E B2ACVIM classi f icat ion� Murmur and cardiomegalypresent

From the panel� Consensus: None� Majority: ACE inhibitor� Majority: Highly palatable,mildly sodium-restricted diet

� Majority: Against use of beta-blocker, pending clinical trials

For my pat ientsMy viewpoint is controversial,2 asI prescribe an ACE inhibitor at thisstage of the disease because of anabundance of supporting evi-dence.3,4 In an unpublished surveyof 100 board-certified veterinarycardiologists, almost 60% prescribedACE inhibitors in small breeds ofdogs and nearly 70% prescribed thedrugs in large breeds at this stage.5

For some of my more dedicatedowners, I often prescribe up-titra-tion of a beta-blocker and wouldconsider adding spironolactone. Ibase the latter approach on recentresearch conducted at North Car-olina State University College ofVeterinary Medicine. This studyindicates that “aldosterone escape”can occur when benazepril is used inhealthy dogs that are undergoingfurosemide-induced activation ofthe renin–angiotensin–aldosteronesystem (RAAS).6

How I Treat / NAVC Clinician’s Brief / July 2011 .....................................................................................................................................................................................55

S T A G E CaACVIM classi f icat ion� Acute heart failure requiringhospitalization

From the panel� Consensus: Furosemide (PO, IM,IV, or CRI7,8)

� Consensus: Pimobendan� Consensus: Oxygen via cage ornasal cannula

� Consensus: Mechanical removalof thoracic or abdominal fluid

� Consensus: Relieve dyspnea/discomfort via appropriatehumidity, environmental temper-ature, and body positioning

� Consensus: Sedation withbuprenorphine and/or acepro-mazine or morphine

� Consensus: Nitroprusside (amixed vasodilator) and/or dobut-amine (inotropic effect, afterloadreduction, reduction of mitralorifice size) via CRI

� Majority: ACE inhibitor, basedon human research evaluating IVenalaprilat (the active metaboliteof enalapril)9,10 and the results ofthe IMPROVE trial11

For my pat ientsI was in the minority in advocatingthe use of nitroglycerin in patients atthis stage of the disease. I believethat additional off-loading therapyis beneficial and can be used in placeof nitroprusside, which can be cum-bersome (requires protection fromlight; CRI; shelf-life of 24 hoursafter reconstitution; blood pressuremonitoring). Otherwise, my treat-ment approach is the same as that ofthe panel as a whole.

S T A G E CcACVIM classi f icat ion� Chronic heart failure requiringat-home care

From the panel :� Consensus: “Triple therapyapproach”—furosemide PO,ACE inhibitor,11-16 andpimobendan17

� Consensus: Against beta-blockerin patients with signs of heartfailure

� Majority: Highly palatable,mildly sodium-restricted diet

� Majority: Spironolactone (seeLate-Breaking Data)

� Majority: Digoxin for cardiacinotropic support and to slow theventricular response to atrial fib-rillation in dogs so afflicted

For my pat ientsMy personal approach to Ccpatients is to use triple therapy aswell as spironolactone. This wouldbe accompanied by moderatesodium restriction in a well-balanced commercial canine diet.

LATE-BREAKING DATAThe consensus statement was prepared before the publication of a placebo-controlled, double-blind study that demonstrated thepositive impact of spironolactone when added to standard therapy in dogs with heart failure.18 The panel may have reached con-sensus on the use of spironolactone in dogs with stage C disease if this information had been available during our deliberations.

CONT INUES

DaACVIM classi f icat ion� Refractory heart failure requiring hospitalization

From the panel� Consensus: Maximum recommended or tolerated doses of furosemide,pimobendan, and an ACE inhibitor, assuming already in therapeutic regimen

� Consensus: When indicated, antiarrhythmic should be used before a patientis considered refractory to standard therapy

� Consensus: Additional furosemide (IV, IM bolus, or CRI) until respiratorydistress has decreased or for a maximum of 4 hours if renal function isadequate

� Consensus: Fluid removal from chest or abdomen as needed to aid inrespiration/comfort

� Consensus: Relieve dyspnea/discomfort via appropriate humidity, environ-mental temperature, and body positioning (assumed from Stage Ca recom-mendations)

� Consensus: Sedation with buprenorphine and/or acepromazine or morphine(assumed from Stage Ca recommendations)

� Consensus: Mechanical ventilation and oxygen supplementation� Consensus: Vigorous afterload reduction in dogs that can tolerate arterialvasodilation (nitroprusside, hydralazine, amlodipine)

� Consensus: Nitroprusside (a mixed vasodilator) and/or dobutamine (inotropiceffect, afterload reduction, reduction of mitral orifice size) via CRI

� Majority: ACE inhibitor, based on human research evaluating IV enalaprilat(the active metabolite of enalapril)9,10 and the results of the IMPROVE trial11

(Note: this applies to cases not receiving an ACE inhibitor when admitted tothe hospital)

For my pat ientsMy approach to Stage Da patients includes the already prescribed ACEinhibitor and spironolactone. Oral furosemide would be replaced withfurosemide CRI, and heart rate and rhythm would be controlled with drugssuch as digoxin, lidocaine, and/or sotalol. Beta-blocker, if previously initiated,would be continued but would not be instituted at this phase.

Further off-loading therapy would include nitroprusside or the combination ofnitroglycerin and amlodipine, depending on severity of signs. Inotropic supportmight include pimobendan (with a dose increase if previously prescribed) and/ordobutamine CRI. Sedation, mechanical fluid removal, ventilation, and oxygentherapy would be used as needed and described above.

It is important to emphasize that each case is different and the therapeuticrequirements vary. No cookbook formula can be provided other than the use of“triple therapy” here. It is also important to understand that while most patientsin Da stage will be on cardiac therapy, some will not.

How I Tre a t CONT INUED

56 .....................................................................................................................................................................................NAVC Clinician’s Brief / July 2011 / How I Treat

S T A G E S T A G E DcACVIM classi f icat ion� Refractory heart failure requiringat-home care

From the panel� Consensus: Continue triple therapy asadjusted in stage Da

� Consensus: Increase dose of furosemideas needed to ease pulmonary edema orbody cavity effusions

� Consensus: Monitor renal function Q 12to 24 H after dose increase to gaugerenal dysfunction

� Consensus: Spironolactone, if notpreviously initiated

� Consensus: Against beta-blockade unlesssigns of heart failure can be controlled

� Consensus: Highly palatable, mildlysodium-restricted diet

For my pat ientsMy approach to the refractory patient thathas returned home would include maxi-mum dose of an ACE inhibitor, continua-tion of spironolactone, and higher doses offurosemide and/or additional diuretics,such as hydrochlorothiazide or torsemide.

Pimobendan would be continued and thedose increased as needed to maintain a statefree of clinical signs. An antiarrhythmicagent would be prescribed when needed, asmentioned above, and sodium restrictionmay be intensified.

Beta-blocker would be used only if initiatedprior to decompensation. I would use tho-racentesis and abdominocentesis as needed,and I would add sildenafil to the regimen ifpulmonary hypertension is present.

Nutraceuticals, such as fish oil, may beadded to help avoid or reverse cardiaccachexia.

How I Treat / NAVC Clinician’s Brief / July 2011 .....................................................................................................................................................................................57

How Clarke Atkins Does It

ACE = angiotensin-converting enzyme,CVHD = chronic valvular heart disease,IMPROVE = invasive multicenter prospectiveveterinary evaluation of enalapril study,MRB = mineralocorticoid receptor blocker

Stage A CVHD (At r isk)� No treatment� Remove from breeding stock� Advise client about disease progress& what to expect

Stage B1 CVHD(Murmur and noenlargement)� Diet: Mild sodium restriction� Blood pressure: Possible hyperten-sion control (eg, ACE inhibitor,usually with amlodipine)

Stage B2 CVHD(Murmur & enlargement)� ACE inhibitor� Beta-blocker� Possibly MRB (spironolactone)

Stage Ca CVHD(Fai lure or history offa i lure: hospita l ized)� Nitroglycerine therapy� Diuretic (furosemide)� ACE inhibitor� Pimobendan� Oxygen� Dobutamine� Thoracentesis or abdominocentesis� Sedation� Relief of dyspnea

Stage Dc CVHD(Refractory: at home)� Diuretic & MRB (furosemide[higher doses] & spironolactoneand/or additional hydrochloro-thiazide or torsemide)

� ACE inhibitor (perhaps increaseddose)

� Pimobendan, typically at anincreased dosage

� Antiarrhythmic as previouslydescribed

� Monitor renal function� Spironolactone� Greater dietary sodium restriction� Beta-blocker continued (but notinitiated)

� Sildenafil with pulmonaryhypertension

� Nutraceuticals for cachexia� Thoracentesis or abdominocentesis

CANINE CVHD—IDEALLY A SURGICAL DISEASEIdeally, severe canine CVHD is a surgical disease, but valve repair or replacementefforts have not been met with adequate success. Recent case studies have shown thatsurgical mitral valve repair has resulted in high perioperative mortality19 and surgicalvalve replacement has resulted in postoperative thrombus formation,20 but there havebeen some individual successes. However, the cost, small number of participatinghospitals, and limited success have rendered surgical correction of canine CVHDimpractical, leaving it as a medically managed disease in veterinary medicine for theforeseeable future.

Stage Cc CVHD(Fai lure or history offa i lure: at home)� ACE inhibitor� Diuretic (furosemide)� MRB (spironolactone)� Pimobendan� Moderate sodium restriction

Stage Da CVHD(Refractory: hospita l ized)� Diuretic (furosemide CRI) asneeded

� ACE inhibitor (continue orinstitute)

� MRB (spironolactone)� Inotropic support (pimobendan ordobutamine CRI)

� Antiarrhythmic agent as indicated(digoxin, diltiazem, lidocaine,sotalol)

� Relieve dyspnea� Sedation� Nitroprusside or nitroglycerin& amlodipine

� Oxygen� Ventilation� Beta-blocker continued (but notinitiated)

� Thoracentesis or abdominocentesis

Capsu le s CONT INUED FROM PAGE 39

The most commonly used drugs and protocols for immune-mediated diseases have been adoptedfrom human medicine, often without the benefit of prospective studies in dogs and cats. This in-depth review details current understanding of the immune system with respect to autoimmunity.The authors then extensively review published data on the treatment of 5 important immune-mediated diseases in dogs: immune-mediated hemolytic anemia (IMHA), immune-mediatedthrombocytopenia (IMTP), acquired myasthenia gravis (AMG), glomerulonephritis, and inflamma-tory bowel disease (IBD).

The pathophysiology of IMHA is complex. Case studies indicate that the thromboembolic state thatoften accompanies or follows IMHA is a major cause of death. Prospective clinical studies fortreatment of IMHA have evaluated cyclosporine, danazol, and azathioprine in IMHA used in con-junction with glucocorticoids and shown no benefit over prednisone alone. Azathioprine has notbeen used in prospective studies, but retrospective studies suggest a beneficial effect over pred-nisone alone. By contrast with IMHA, clinical signs of IMTP can be fairly mild and most patientsrespond well to glucocorticoid therapy. The only additional drugs evaluated prospectively in con-trolled studies were vincristine and intravenous immunoglobulin (IVIG), both used in combinationwith glucocorticoids. Dogs receiving prednisone and IVIG had significantly higher platelet countsand shorter hospitalization stays than those receiving prednisone alone. A small study showedvincristine to be an effective adjunctive therapy for stimulating platelet production. Leflunomideand cyclosporine were separately shown to have some efficacy; however one dog receivingcyclosporine died of systemic aspergillosis, possibly secondary to immunosuppression.

AMG is frequently associated with other immune-mediated and neoplastic diseases. The authorspoint out that it has the potential for spontaneous remission, creating a significant confoundingfactor in clinical studies. Glucocorticoids have been used but the side effects are of significantconcern (muscle weakness, aspiration pneumonia). Azathioprine alone or with prednisone hasbeen associated with better survival rates. Cyclosporine has also been used in a small number ofcases as part of combination therapy or following glucocorticoid therapy. Canine glomerulonephri-tis is an immune-complex–mediated disease. True autoimmune glomerulonephritis is rare. Thereis no evidence that immunosuppressive therapy is of benefit and it may be detrimental. IBD is acomplex disease and little evidence exists that this is a true autoimmune disease. Manipulation ofexogenous antigens in contact with the mucosa and control of the inflammatory response arecornerstones of treatment.

CCoommmmeennttaarryy:: These drugs represent what is available today to treat immune-mediated diseases.Their overall effect on the immune system is nonspecific, which can lead to compromise of otherareas and unfortunate complications (ie, susceptibility to infection). New technologies from humanmedicine that are more target specific are being studied. One example is canine recombinantinterferon-gamma that “rebalances” the activity of Th1 and Th2 lymphocytes for the managementof canine atopic dermatitis. Another example is the use of a peptide vaccine to treat dogs withspontaneous myasthenia gravis.—Karen A. Moriello, DVM, Diplomate ACVD

Immunomodulatory drugs and their application to the management of canine immune-mediated disease. WhitleyNT, Day MJ. J SMALL ANIM PRACT 52:70-85, 2011.

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Drug Efficacy in Immune-Mediated Diseases

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Mechanical stretching of the skin by creating aconstant load over time results in cellulargrowth and tissue regeneration. This phenome-non is typically seen in pregnancy, skin growthover benign tumors, and obesity. Preoperativeskin stretching has been described in dogs andcats. In this report, a 7-year-old male dog wasevaluated for 2 wounds—1 in the right cervicalarea, the other on the right antebrachium—sustained during a dog fight. The wounds weresevere. The right cervical wound was 8 cm longand extended 10 cm ventrally from the dorsalmidline. The right antebrachium was devoid ofskin from the elbow to the carpus except for asmall piece extending distally from the elbowand another thin strip on the craniomedialaspect of the limb. Neither wound was infected

and both had a healthy granulation bed. Skinstretchers were placed on the patient’s back,and the owners were instructed to gently tightenthe cables daily if there was a loss of tension.After 4 days, the dog was admitted for woundrepair. The skin stretchers had created approxi-mately 8 to10 cm of additional skin. The flap forwound reconstruction was created over the rightcaudal shoulder area, allowing preservation oflocal blood supply and the right thoracodorsalartery and vein. The flap was then rotated 180°into the wound and sutured to the distal ante-brachium. Drains were placed under the base ofthe flap exiting caudal to the elbow and wereremoved 4 days after surgery. The dog was dis-charged 5 days after surgery and at 5 monthsthe flap was intact and completely healed.

CCoommmmeennttaarryy:: Preoperative skin stretching is atechnique that has been used in human recon-structive surgery for procedures as varied asextensive oncologic resections to the separationof conjoined twins. The system mentioned in thiscase report was originally described by Pavleticmore than a decade ago. It is easy to use andavoids the significant expense and increasedmorbidity of temporary inflatable subcutaneousimplants. Although the theory is a little complex,the application of skin stretching is a relativelysimple technique that is undoubtedly underuti-lized in veterinary surgery.—Art Fettig, DVM,Diplomate ACVS

Use of skin stretchers to elongate a peninsular thoraco-dorsal axial pattern flap for antebrachial wound closure in a dog. Holt DE, Runge J. VET SURG 40:352-356, 2011.

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Cefpodoxime proxetil (Simplicef, pfizer.com) is aonce-daily orally absorbed antibiotic with a widespectrum of activity that is widely used to treatskin infections. It is a third-generation cephalo-sporin that in the intestine is cleaved into theactive metabolite cefpodoxime. In this study, thecefpodoxime concentrations in plasma, subcuta-neous (SC) tissue, and urine were determinedusing a crossover design. Dogs received 2 doselevels of cefpodoxime proxetil (6.5 mg/kg and13.0 mg/kg; the equivalent of 5 mg/kg and 10mg/kg cefpodoxime, respectively) with a 1-weekwashout period between doses. Blood sampleswere collected from a cannulated cephalic vein,urine was collected via a Foley catheter, and asterile microanalysis probe was used to obtainsamples from the SC tissue. The mean maxi-mum concentration in plasma was 13.66mcg/mL and 27.14 mcg/mL at 5 mg/kg and 10mg/kg cefpodoxime, respectively. Cefpodoximewas widely distributed to the skin with maximumconcentrations of 1.70 mcg/mL (5 mg/kg dose)and 3.06 mcg/mL (10 mg/kg dose). The drug was

excreted essentially unchanged in the urine withcumulative percentages of unchanged cefpo-doxime at 72.2% and 95.8% at the 5 mg/kg and10 mg/kg doses, respectively. Based on thesestudies the authors recommend a dose of 10mg/kg for skin infections for bacteria with anMIC50 (minimum inhibitory concentration) up to0.5 mcg/mL. Higher and more frequent dosingwould be needed for bacteria with higher MICvalues. These data suggest that this drug wouldbe useful in treating urinary tract infections(UTI). Supported by Pfizer Animal Health

CCoommmmeennttaarryy:: The pharmacokinetics of cefpo-doxime in dogs was evaluated in this study,focusing specifically on plasma and SC distribu-tion after a single oral dose. The concentrationof cefpodoxime in urine was also measured todetermine whether the drug might be useful intreating UTI in dogs. Cefpodoxime was elimi-nated mostly in the urine and in high concentra-tions, which suggests that it may indeed beeffective for UTI in dogs, although this requires

further evaluation. This study also suggests thatcefpodoxime rapidly achieves good penetrationof the skin, has a half-life of 3 to 5 hours, andpersists in the tissue for up to 22 hours followingadministration. Pharmacokinetic data indicatethat cefpodoxime should be effective againstcertain microbes (MIC50 < 0.5 mcg/mL); how-ever, for microbes with a higher MIC50, cefpo-doxime should be administered at a higher doseor with increased frequency for effective treat-ment. The importance of pharmacokinetic stud-ies to optimize antimicrobial therapy and ofobtaining culture and sensitivity data to makethe most appropriate choice of antibiotic anddosing schedule are highlighted here.—JenniferGinn, DVM, Diplomate ACVIM

Pharmacokinetics of cefpodoxime in plasma and subcu-taneous fluid following oral administration of cefpodoximeproxetil in male beagle dogs. Kumar V, Madabushi R,Lucchesi MBB, Derendorf H. J VET PHARMACOL THER34:130-135, 2011.

Skin by a Stretch

Utility of Cefpodoxime

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