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Anesthetics and the Veterinary Practice:

Experts discuss current applications of anesthetics and preoperative medications

Information provided by Abbott

Only SevoFlo--available through all major distributors--provides four unique benefits:

1. A minimum of 300 ppm water 2. Shatter-resistant PEN bottles 3. Local Abbott representatives and expert advice 4. Commitment to training and education

The SevoFlo Difference

SevoFlo brings four added benefits to every procedure. You trust SevoFlo in the surgical suite because you know it works. But did you realize that every time you use SevoFlo you're getting unique benefits? SevoFlo includes four key benefits that make it a smart choice for your practice: · SevoFlo contains a minimum of 300 ppm water. SevoFlo's high water content can effectively inhibit the degradation of sevoflurane by Lewis acids. This degradation can result in by-products (such as hydrogen fluoride1) which may damage equipment, including certain types of vaporizers. · SevoFlo is packaged in shatter-resistant plastic polyethylene naphthalate (PEN) bottles. Unlike glass bottles, PEN bottles are shatterresistant and do not contain Lewis acids. · SevoFlo has local representatives and expert advice. Count on our local Veterinary Practice Consultants for product support and advice. Also, our technical support department and panel of anesthesiologists are standing by to help and advise regarding techniques, products and equipment. · Abbott Animal Health, provider of SevoFlo, is committed to training and education. Rely on Abbott for in-clinic training and materials--such as the Anesthesia Value Program--and sponsorship of CE events to help you provide the best possible care. When choosing an anesthetic, ask yourself if you're getting all these benefits SevoFlo delivers. To learn more about the SevoFlo difference, contact Abbott Animal Health Customer Service at 888-299-7416 or visit www.AbbottAnimalHealth.com.

Important SevoFlo Risk Information: Warnings, Precautions, and Contraindications: Sevoflurane is a profound respiratory depressant. Respiration must be monitored closely in the dog and supported when necessary with supplemental oxygen and/or assisted ventilation. Due to sevoflurane's low solubility in blood, increasing concentration may result in rapid hemodynamic changes compared to other volatile anesthetics. SevoFlo is contraindicated in dogs with a known sensitivity to sevoflurane or other halogenated agents. Adverse Reactions: The most frequently reported adverse reactions during maintenance anesthesia were hypotension, followed by tachypnea, muscle tenseness, excitation, apnea, muscle fasciculations and emesis. See package insert for full prescribing information. Note: The FDA has determined that generic animal drugs that are classified as bioequivalent can be substituted with the full expectation that the substituted product will produce the same clinical effect and safety profile as the reference product. Indications: SevoFlo is indicated for induction and maintenance of general anesthesia in dogs. How Supplied: SevoFlo is packaged in amber colored bottles containing 100 mL or 250 mL sevoflurane.

©2010 Abbott Laboratories

1. Anesthesia Analgesia 2007;104;1447-51

See prescribing information on page 13.

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About the Authors

Dr. Tamara Grubb,DVM,MS,DACVA isanassistantprofessorintheCollegeof VeterinaryMedicine,VeterinaryClinicalScienceat WashingtonStateUniversity,Pullman,WA,anda board-certifiedveterinaryanesthesiologist. Dr. Gwendolyn Light Carroll,DVM,MS, DACVA,CVA,isaprofessorofAnesthesiology atTexasA&MUniversityCollegeofVeterinary MedicineandBiomedicalSciences,Departmentof SmallAnimalClinicalSciences,CollegeStation,Texas. Dr. James Gaynor,DVM,MS,DACVA, isprincipalinPeakPerformanceVeterinary Group,ColoradoSprings,CO,inadditiontotwo emergencyveterinarypractices.Heisboard certifiedinveterinaryanesthesiologyandcertified inveterinaryacupuncture. Dr. William W. Muir III,DVM,MS,PhD, DACVA,DACVECC,servesastheresearch directorfortheU.S.-basedResearchMedications andTestingConsortium(RMTC),whilealso advisingandworkingatseveralreferralequine practices.Hewasaprofessorinthedepartment ofVeterinaryClinicalSciencesatOhioState Universityfor37years. Dr. Bruno Pypendop,DACVA,isan associateprofessorinthedepartmentofSurgical andRadiologicalSciencesattheUniversityof California-DavisSchoolofVeterinaryMedicine.His appointmentissplitevenlybetweenclinicaltrials andresearch.Hestudiestheclinicalpharmacology ofanestheticsandanalgesicagentsinanimals, particularlycats. Dr. Fred Metzger,DVM,DABVP,isprincipal intheMetzgerAnimalHospital,afour-doctor practiceinStateCollege,PA.Inaddition,heis anadjunctprofessoratPennStateUniversity andservesonthepractitioneradvisoryboards ofVeterinary EconomicsandVeterinary Medicine magazines. AbbottAnimalHealthwouldalsoliketo acknowledgeDr. Christina Barcus,DVM,a veterinarianandownerofCanineSportsCenter inLakeVilla,IL,forhercontributiontothispiece.

About the Topics

Inmanycases,goodanesthesiaiswhatcanstand betweenadesiredoutcomeandmorbidityormortality. Inanefforttogatherawideperspectiveonthisimportant topic,AbbottAnimalHealthtalkedwithadistinguished panelofexpertsinveterinaryanesthesia.Theircomments arecandidandaddressquestionsveterinariansareasking aboutanestheticseveryday.Thispiecereviewsthefollowing: · eterinaryanesthesiaisachangingandever-advancing V science.Periodicallyre-evaluatinganesthesiachoices, methodsandmonitoringtechniquesisimportantfor everyveterinarypractice. ·ssuesthatariseduringanesthesiamaybedifficult I toidentify;activepatientmonitoringandemploying dosing-to-effectstrategiescontinuetobecritical aspectsofensuringconsistency,qualityandbest- medicinepatientcare. · ndfinallythere'sthefinancialpiece,whichdescribes A anesthesiaasaprofitcenter.Thebusinesssideof veterinarymedicinehasneverbeenmorechallenging, butincludinganestheticsasarevenuechannelcanplay animportantroleinmakingyourpracticeefficient. Anesthesiacanandshouldbeprofitable.

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Anesthetics and the Veterinary Practice

The Goal of Anesthesia -- Morbidity vs. Mortality

Sciences,DepartmentofSmall AnimalClinicalSciences,yearsago theobjectivewastogetpatients throughtheprocedure.Nowthe objectiveisaprocessthatcontrols pain,alongwithprovidingan anestheticthat'ssmooth,safe Virtuallynoaspectofveterinary andpredictable. medicineismoreimportanttoa "Wereallyconcentrateon goodoutcomeinanimalsurgery returningthepatientmaybeeven thanproperuseandmonitoring alittlebetterthanthewaywegot ofanesthetics.Soworkingtoward itratherthanthepatientnotbeing betterimplementationof inasgoodashape,"Dr.Carroll anesthesia,fromdrugdeliveryto said."Oftenwe'llgetapatient monitoring,iskeytosuccessful who'sanemergencypatient in -- surgeryandasuccessfulpractice. shockorvolumedepletedwith Safeandeffectiveanesthesia respiratorycompromise.Andifyou providesanopportunityfor can'tstabilizethepatientpriorto bettersurgery,andfasterand anesthesiathenit'sincumbenton morecomfortablerecovery. us,theanesthetist,togivefluidsand trytoreturnthatbodytoamore homeostaticnaturethanwhenwe What is Good gotthepatient." Anesthesia? Goodqualityanesthesiaconsists ForDr.TamaraGrubb,assistant ofavarietyofcomponents, professorintheCollegeof includingmusclerelaxation,lack VeterinaryMedicine,Veterinary oforgantoxicity,reasonable ClinicalScienceatWashington cardiopulmonaryfunction, StateUniversity,goodanesthesia unconsciousness,lackofawareness, issafeanesthesia."Mygoalisto andsmoothinductionandrecovery. titratetheanestheticdrugsto Agoodprocedurebringsideal thepointthatthepatientisatan appropriateplaneofanesthesiafor hypnosisandanalgesiatominimize stressandanxiety.Andthatstateof theparticularprocedure.Idon't optimalanalgesiashouldcarryinto wantthepatienttoodeeportoo light;Idon'tconsidereitherofthose thepostoperativeperiod. "Fromananesthetist'sperspective goodanesthesia." Thedefinitionofgoodanesthesia it'simportanttogetasmooth inductionandsmoothrecovery,and haschangedovertheyears. thusstablemaintenance,"saidDr. AccordingtoDr.GwendolynLight Carroll,professorofAnesthesiology BrunoPypendop,associateprofessor, atTexasA&MUniversityCollegeof UniversityofCalifornia-Davis,School VeterinaryMedicineandBiomedical ofVeterinaryMedicine,Department ofSurgicalandRadiologicalSciences. "Ithinkit'simportanttoavoid worseningthepatient'scondition duringsurgery,andifatallpossible, improvingtheirconditionduring anesthesiabecausewecandeal withconditionslikeelectrolyte disturbances,fluidandacid- baseimbalances." Anesthetics,likeother pharmaceuticals,comewith risk.Factorsincludethepatient, theanestheticdrugsinvolved andthesurgicalprocedure. Commonanestheticrisksinclude hypotension,hypoventilationand cardiacarrhythmia.

Managing the Risks

AccordingtoDr.JamesGaynor, founderofthePeakPerformance VeterinaryGroupinColorado Springs,"We'realwaystryingto usedrugsthathavefewerrisks andagreatertherapeuticindex (properties).Thewaytheserisks aremanagedisbypreventing themandthewaythey're preventediswithgoodhuman attentiontodetail,"hesaid. "Thatattentiontodetailincludes understandingwhatwe'redoing: whetherit'sadrugoraprocedure, knowingwhattherisksareand beingabletopredictwhatcould happen.Wedon'twantproblems tobecomecomplications." It'sknownthatnomatterwhat agentisused,gasanesthesia producesadose-dependent decreaseincardiacoutputand lowerbloodpressure.It'snecessary

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torecognizeandacknowledgethis riskfactor. "WegivethepatientIVfluids,we monitorthemsowe'relookingfor cardiacissues,weknowwhatthe cutoffisandwhattheacceptable decreasesinbloodpressureare andhowtotreatitifitoccurs," Dr.Gaynorsaid."Bloodpressureis thenumberonethingweneedto beconcernedaboutbecauseit's themostcommonissue." Otherrisksforananimalthat's diseasefreebutunderanesthesia includedepressionofthe cardiovascularortherespiratory systems--systemsthatarethe mostimportantintermsoftissue perfusionandrequiremonitoring duringanesthesia."What'sreally importantistomonitorwhat you'redoingandbasicallymake adjustmentsaccordingtothe

organduringasurgicalprocedure. Thepatientcanexperiencerenal insufficiency,hepaticdysfunction, myocardialcompromiseoravariety

"We don't want problems to become complications."

Dr. James Gaynor, MS, DACVA

patient,"Dr.Pypendopsaid."You shouldn'trunonautopilot." Decreasedtissueperfusionisa frequentsequeltoanesthesia. Thisprocessmeansdecreased oxygendeliverytothetissues; selectanorganandimaginethe consequencesofhypoxiainthat

ofotherconditionsthatthreaten boththeprocedureandtheanimal. "Apatientthatwakesupblind ordeaf--thesecasesareeasyto linktoanesthesia,"Dr.Carrollsaid. "Buttheoldcatincompensated renalfailurethatcomesinfora dental,andreturnsinafewdays

withacuterenalfailurebecause ofpoorkidneyperfusion;the veterinarianmaynotthinkitwas theanesthesia.Thosearetheones thatarearealheartbreaker.It's totallyavoidable.It'ssomethingyou canavoidbypreparingthepatient andmonitoringthepatient." Lowtissueperfusionistypically adose-dependentresponseto thegasanesthetic.Thehigherthe gasanestheticconcentrationin thebodythelessbloodthe heartpumpsperminute."Cardiac outputiskey--thelowerthe cardiacoutputthelowerthe tissueperfusion,"Dr.Gaynorsaid. "What'simportantisgetting oxygentothetissuesandmetabolic byproductsoutofthesystem. Whenthereisn'tenoughoxygen deliverytothekidneysthenwecan getdamage.Andthekidneysdon't regenerateeffectively."

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Anesthetics and the Veterinary Practice

Dr.WilliamMuir,researchdirector fortheU.S.-basedResearch MedicationsandTestingConsortium (RMTC),takesthekidneydiscussion astepfurtherinlinkinganesthetic inducedhypotensiontoaprolonged recovery."Anotherconsequence ofdecreasedtissueperfusionisthe potentialforanaerobicmetabolism andthedevelopmentoflactic acidosis,whichcanamplifypain andpredisposetoelectrolyte imbalances." fortheprocedure.Inadditionto administeringtherequireddrugs andmonitoringthepatient,the anesthetistmanytimesactsasthe advocateforthepatient,lookingat theoverallsituationinawaythat thesurgeoncannot. "Ilookatcontrollingpain, ensuringthepatient'ssafety preoperatively,intraoperatively andpostoperatively.Ifthey needsupportinanyperi-or postoperativeperiodIliketothink that'smyjob,"Dr.Carrollsaid. Again,akeycomponentof goodanesthesiaisanticipating anypotentialcomplication.The surgeon'sroleistofocusonthe surgicalprocedure,whichmay makeitimpossibletokeeptrack ofthestatusofthepatient.The anesthetistislookingatthebig picture--patient,drugs,procedure, status,postoperativenextsteps, recovery."There'sanoldquote: `Therearenosafeanesthetic drugs,therearenosafeanesthetic procedures;thereareonlysafe anesthetists.'Andthat'sreallytrue becausewecantakeanydrug andkillapatientwithitifused inappropriately,"Dr.Gaynorsaid. practitionersdon'tdodosingto effect,"Dr.Grubbsaid."Theyhave adoseandtheyhaveasettingon theirvaporizerdialandthat'swhat theydoinsteadofusingpatientneededanesthesia." Withoutdosingtoeffectit'seasy tooverdoseapatient.Eachpatient isuniqueandrequiresadifferent levelofanesthetic.Andanesthetic drugscancausesideeffects,sothe highertheleveloverthedosethe morelikelythepatientistosufferan unwantedresponse. Thereareanestheticdrugsthat produceadependableeffectin arelativelyshortperiodoftime, accordingtoDr.Muir.Hecites propofolasagoodexample becauseitsonsetofeffectis relativelyrapidbaseduponitsability togetintothebraintoproducean effect,butthatinfluenceisrelatively shortlivedmeaningthedruggets in,doesitsjobandisthengone. Forhim,thebestanswerisadrug thathasapredictableeffect,arapid onsetandarapidoffset.

Anesthetic Management, Monitoring Administration

AccordingtoDr.Grubb,the roleoftheanesthetististokeep thepatientsafewhiletitrating anestheticdrugstomaintainan appropriateplaneofanesthesia

The Right Amount

Dr. Tamara Grubb

Sincemostanesthetic drugscausedose-dependent complications,thebestwayto deliversafeanesthesiaistoprovide onlytheamountofadrugthe patientneedstoachieveasecure surgicalplane."Unfortunately,I thinkalargepercentageofgeneral

Dr. William W. Muir III

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"We're really far, far away from the one-dose-fits-all sort of mentality..."

Dr. Gwendolyn Light Carroll, MS, DVM, DACVA, CVA

soyou'refarbetteroffifyoucan givedrugsthatyoucantitrate toeffect.Soifyouhaveaseptic patientoranoldpatientorayoung patientandyoucangivethemthe appropriateamountofdrugswith theappropriateadjuncts,thenyou reallycanoptimizeeffectsandnot givemorethanthey'regoingto need.We'rereallyatthepointwhere it'snotacookbookanymore."

Monitoring the Body

Dr. Gwendolyn Light Carroll

"We'rereallyfar,farawayfromthe one-dose-fits-allsortofmentality. Itusedtobethatifyouhadadrug andyougaveitintramuscularly, itwasinthepatient--thenyou

werefreefromallresponsibility becauseyoucouldn'tgetitback," Dr.Carrollsaid."Andevendrugs thatcanbeantagonized,thebody hastodealwiththosedrugsand

Anestheticdrugshavethe potentialtocauseadecreasein functionofallphysiologicalsystems, butanegativechangeinfunction forthecentralnervoussystem, thecardiovascularsystemandthe respiratorysystemwouldbethe mostimmediatelylifethreatening. Somonitoringshouldbefocused onthesesystems. "Heartrateandrhythm, respiratoryrateandcharacter,pulse, pulsequality,bloodpressure--those arethethingswealwaysmonitoron everypatientthatisanesthetized. Welookforsignstodetermine wakefulnessandreflexestoseewhat theplaneofanesthesiais.Additionally, weactuallyhavetheluxuryof monitoringpulseoximetryonour patients,especiallyduringtransport," Dr.Carrollsaid.Thestatusofthe patientdeterminesifanythingelse shouldbemonitored.Forexample, ifapatientisinrenalfailure,urine outputwouldbemonitored;ifthey're havingproblemswithelectrolytes, thenpHandbloodgasanalysis requireadditionaloversight.

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Anesthetics and the Veterinary Practice

"Iagreethatthemainfocus wouldbeoncardiovascularand respiratory,butIwouldaddthat weneedtomonitordepthof anesthesiaaswell,"Dr.Pypendop said."Bodytemperatureisanother aspectthat'simportanttomonitor becauseit'sbeenshownthat hypothermiahasmanydetrimental effects,soit'sadangeraswell." Withmonitoringofvitalorgans addressed,thenextemphasisarea isadministeringtheanestheticdrug. Vaporizerscanbeusedinasimilar waytoadministeranintravenous drug.Thevaporizersettingsneed tobealteredifthepatientiscold;if therearedepressantsonboardlike analgesicsortranquilizers;ifthere

" You arrive at the appropriate vaporizer setting based upon patient requirements and then provide just enough anesthesia to complete the surgical procedure."

Dr. William W. Muir III, DVM, MS, PhD, DACVA, DACVECC

arehighlevelsoftestosterone;orif thepatientisextremelyyoungor extremelyold. "ThewayItraintechniciansand veterinariansongasanesthesia isthatyoualwayshaveastarting point,"Dr.Gaynorsaid."Ifwetake sevofluraneforinstance,patients

thathavebeenpremedicated withanopioidandinducedwith propofol--Istartthematfive percentsevoflurane.Threelitersof oxygenisfastenoughtogetinto thesystem,throughthecircuit;five percentallowssevofluranetostart comingthroughsowehaveenough

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gettingtothebrainbeforethe propofolwearsoff. "Fromthereeverybodyneeds torecognizethatgasanesthetics aredrugsthatweusetoeffect.The vaporizerisadynamictool;it'smade tobechanged.Whenpeoplesay, `anesthesiawentgreat,Ineverhad totouchthevaporizer'thatmeans thepatientissomewherebetween adequatelyanesthetizedandjustthis sideofdeathbecausethevaporizer wasneverturneddown." Dr.Muirreinforcedthe importanceofmanagingthedepth ofanesthesiawhenhesaid,"What you'relookingforisavaporizer settingthatallowssafeandeffective surgerytobedone,andthat's dependentuponthesurgical procedureandpatientstatus.By wayofexample,iftheprocedure isanendoscopicexamination,the inhaledconcentrationofvolatile anestheticorvaporizersetting couldberelativelylowcompared toasurgicalprocedurethatismore painfullikeputtingbonesbackin properalignment.Youarriveatthe appropriatevaporizersettingbased uponpatientrequirementsandthen providejustenoughanesthesiato completethesurgicalprocedure." Generalrecommendationsfor administeringanestheticdrugsor selectingthecorrectvaporizer settingmustbemodifiedtofit patientrequirements.There'sno idealrecipeforeverypatient.The objectiveistoproduceadepthof anesthesiathatresultsinadequate musclerelaxation,analgesiaand

hypnosis(unconsciousness)and maintainsadequatevitalsigns. Variouspreanesthetic medicationsprovideahuge assisttowardreachingthegoal ofidealanesthesia.Premedicant

Dr. Bruno Pypendop

tranquilizerscalmthepatientand decreasethedoseofinduction andmaintenancedrugsnecessary toachieveandmaintaina surgicalplaneofanesthesia.The administrationofpreanesthetic drugsthatproduceanalgesiaalso providesbettercontrolofpain duringboththeanestheticepisode andpotentiallyintotherecovery period.Adequatepaincontrolhelps topreventroughrecoverieswhen relativelyshort-actingdrugslike propofolandsevofluranewearoff. "Myphilosophyregarding premedicationistouseitwhen youneeditanddon'tuseitwhen youdon'tneedit,"Dr.Pypendop said."Ifyouhaveananimalthat's anxioustostartwith,weknow

thatpremedicationisgoingto improvequalityofinduction,most likelyqualityofmaintenanceand potentiallyqualityofrecovery. Providingpreemptiveanalgesia, startingtogiveanalgesicatthe timeofpremedication,mayhelpto provideamorestablemaintenance andmayhelpinpreventing excessiverecoverythereafter." Thegeneralruleisthatfora majorityofpatientspremedication improvesthequalityofanesthesia. "Reducinganxietyisasimportant forsomedogsasproviding analgesiabecauseofthestress response.Thecortisolresponse fromanxietycanbegreaterthan thatfrompain,"Dr.Carrollsaid."So forsomedogsbeingscaredand frightenedisjustasbadtothemas thediscomfort." Premedicantsclearthepathfor lowerdosesofgasanestheticsand allowlowerdosesofIVinduction agents.They'repartofassociated adjunctsusedtoproduceanideal anestheticstateorabalanced anestheticstate--wherethe patientdoesnotrespondtosurgical manipulations,yetisnotdeeper thanitreallyneedstobe.

General Practitioners Improving Overall Anesthesia Quality

Goodanesthesiapracticeisa matterofknowingthedrugsthat providesafe,reliableanesthesia andthenmaintainingcurrent knowledgeonthosedrugs.There aresafeandeffectivedrugsavailable

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Anesthetics and the Veterinary Practice

todaythatweren'tonthemarket 10or15yearsago.Additionally, Dr.Carrolladvisesinvestmentin agoodmonitorthatevaluates cardiopulmonaryfunction,an oxygendeliverysystemanda laryngoscopeforintubation. Additionally,there'sstrong sentimentamongtheseveterinary anestheticsexpertsthatadedicated resourceshouldmonitorthe patientthroughoutasurgical procedure."Whatoftenhappensis someoneanesthetizesthepatient andthenthey'reoffgettingthe antibioticsandassemblingthe surgerypack.Someonereallyneeds topayattentiontothepatient continually,"Dr.Gaynorsaid."People say,`I'vebeendoingsurgeryand anesthetizingdogsfor150years andI'veneverhadaproblem.'That's becausetheimmediateproblem youcan'tsee.Talktomostofthese practitionersandalmostallhave hadanincidentwheretheyputa 12-year-olddogunderanesthesia andhedidn'twakeupwell,came homegroggyandwasinacute renalfailure.Theythinksomething's wrongwiththedog,whereasthe realityistheyprobablycausedthe problem.Itisaneducationissue forveterinarians." Bycomparison,adedicatednurse anesthetistoranesthesiologistis requiredtomonitorhumanpatients atalltimes.Thisisnotthecase inmostveterinarypractices.This carriesovertopaincontrol,another elementofimprovingoverall anesthesiaingeneralveterinary practice.Dr.Muirhasobserved thatmanygeneralpractitioners aremuchmorecognizantof paincontrolthaninthepastand emphasizesthatpainneedstobe controlled,notonlyduringsurgery, butpostoperativelyaswell. "Ithinkmostveterinariansare veryconscientiousaboutpain control.Theproblemisthatpain controlisusuallythefocusafter thesurgery,notbeforeorduring surgery,"hesaid."Thereareplenty ofreasonsforthat.Manypeople feelthatifthepatientisunconscious theymaynotneedverymuch paincontrol.Inreality,however, Havingatechnicianfocusedsolely onthisprocedureiscostly.Butwhat isthecostforoptimalanesthesia? Forsomepatients,thoseinpain forinstance,reachingoptimal anesthesiamakesabigdifferencein theultimateoutcome.

Protocol, Techniques in Anesthetic Administration

Aspartofgoodanesthetic practice,theimportanceofgood recordkeepingcan'tbeemphasized enough.Anongoingrecordcan alertaveterinariantotrends, changesoradevelopingproblem thatmightnotbenoticedina singlereading.Afterworkingwith apatientforaperiodoftime andeverything'sstable,asudden alterationinrecordedlevelsmeans it'stimetotakeaction. "Aslowchangecanbeeasily missedifrecordsaren'tmaintained," Dr.Grubbsaid."Andslowchanges couldpotentiallyreachacritical pointbeforeanyonenoticesthat something'swrong.Byvisualizing trendsonananestheticrecordwe canmoreappropriatelyevaluate changeinthepatientandreacttothat changebeforeitbecomescritical." Anadagethatappliesinthis caseis,"Ifitisn'twrittendownit didn'thappen." "Clearly,fromamedical-legal perspective,it'simportantto

Dr. James Gaynor

inadequatepaincontrolduring surgerysetsthestageforwhatever happensafterthesurgery.Ifyoudo notcontrolpainfulsituationsearly yougenerallyendupusingalot moredrugduringoraftersurgery, whichcancomplicatetherecovery andpostoperativeperiods." Thereisacostconsiderationin dedicatingananesthesiaresource.

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documentwhatwedowithour patients,whetherit'sanesthesiaor surgery,orjustwhathappensduring anexam,"Dr.Gaynorsaid."Froma medicalperspective,it'simportant thatifsomethinghasgonewell orsomethinghasnotgonewell, wehavedocumentedinformation aboutwhatwedidsowecaneither repeatitorlearnfromit.It'sabout furtheringourknowledge." Dr.Pypendopagreedwhenhe said,"Ifyou'renotrecordingwhat you'redoingitwouldbeveryeasy

fast-actingdrugisadministered, dosedtoeffect,toapatientwho's receivedpreoperativesedativesand isinaquietenvironment. "Thepatient'sphysicalstatusisa keyfactordeterminingthespeed ofinduction,"Dr.Muirsaid."Calm, compliantdogsandcatsneeda lotlessmedicationthanexcited, agitated,fearfulorpainfulanimals. Thisfactorisnotemphasizedas muchasitshouldbe. "Animalsthatareafraidor stressedusuallyrequiremoredrugs

"An adage that applies in this case is, "If it isn't written down it didn't happen."

Dr. Tamara Grubb, DVM, MS, DACVA

tomisstrendsinthevariablesyou monitor.Forexample,aheartrate startsat100and10minuteslater it's105,then110.Itmaykeepgoing upandthatmaybemissedifyou're notactuallyrecording."

Speed of Induction

Avarietyoffactorsaffectthe qualityandspeedofinduction, includingpharmacological,patient andenvironmentalcomponents. Inthebestcase,inductionshould occurrapidlyandsmoothlywithno excitement.Thisisbestachieved whentheappropriatedoseofa

thananimalsthataredepressed," hesaid."Thenthere'sthedelivery equipmentitself--howit'ssetup, whattheanestheticcarriergas-flow ratesarewhenyou'readministering aninhalantanestheticortheinfusion ratesarewhenyou'readministering aninjectableanesthetic.Athird factormaybetheuseofadjuncts --drugsthatareadministered inconjunctionwithinjectableor inhalantanesthetics."

Quality of Recovery

Withqualityofinduction comesqualityofrecovery.This

isnotaprocessthat'sinfluenced byspeed,necessarily.Veterinary medicalprofessionalsarelooking forananimalthatwhenitregains consciousnessisfreeofpain,has goodvitalsignsandisnotstressed. "Theanswertothequestionof recoveryqualityiscomplicated," Dr.Grubbsaid,"becausefast recoveriesandgoodrecoveriesare notnecessarilycoupledtheway fastinductionandgoodinduction are.Wewantthepatienttowake upfromanesthesiarapidly,butwe wantthemtobefreefrompain sothey'recomfortableandcan sleeppostoperatively.Recovery timeisdictatedbysurgerytime. Longsurgeriesgenerallyresultin longrecoveries.Andlongsurgeries meanthatthepatientismorelikely tobehypothermic;hypothermia contributestoprolongedrecoveries." Shesaidthatuseofdrugswhich canberapidlyandeasilyeliminated fromthebodywillhelpspeedthe recoverytimeaswell.Drugslike propofolandsevofluranefitinto thiscategory. "Weknowthatsomedog breedstendtohavepoorquality ofrecoverynomatterwhatyou dointheoperation,"Dr.Pypendop said."Theagentsthemselvesmay playarole;someinjectablesresult inafasterrecoverythansome others.Andsomeinhalantsmay speedrecoverysomewhat.For example,ifyouuseaninhalant anesthetictomaintainanesthesia keepingthegaslow,whenyou discontinueadministrationofthe

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Anesthetics and the Veterinary Practice

inhalantitwillslowdownrecovery. Alternatively,anincreaseinthefresh gasflowmayspeeduprecovery." Ultimately,thefastertherecovery, thefasterthepatientreturnstothe physiologicalnorm.

Human vs. Veterinary Anesthesia

Anydiscussionofveterinary anesthesiabegsacomparisonto howthesedrugsareappliedonthe humanside.Manyofthedrugsare thesame,butapplication,procedure andmaintenanceisvastlydifferent. "Humananesthesiaismuch moreregulatedandthereismore scrutiny,"Dr.Grubbsaid."Inmost waysthepracticeofanesthesiain humansismuchmoreadvanced thanthepracticeinanimals,andthis issomewhatdisappointingbecause thegapshouldn'tbeasbigasitis. Weusethesameanestheticdrugs thatareusedinhumanmedicine andwehaveaccesstothesame typesofdrugsandmonitors. Wejustneedtoraisethebarin veterinarymedicine." ForDr.Carroll,thefactthat recordsarecomputerizedonthe humanside,alongwithanesthesia's incorporationinamonitoring machine,makeshumananesthesia moreadvanced."Theycanprint outarecordofeverybreathtaken oranydrugsreceived.Andthey haveanalgorithmthatcanpredict

ifthepatientisgettinglightorif moredrugsareneeded;whatto doifbloodpressureishighorlow. Muchinthehumanarenaisdriven byinsurancecostsandmalpractice, thingsthatarenotcurrently relevanttotheveterinarian." Allfiveveterinaryanesthesiologists citeddedicatedmonitoringasa fundamentaldifferencebetween animalandhumananesthesia,as wellassophisticationinprocedures, equipmentandtrainedpersonnel. "Iwouldsaythatthebiggest differenceiswhatourgoalsare.In veterinaryanesthesia,frequently ourendpointistoanesthetize patientssothattheydon'tmove, andthatmeansmakingthempretty deep,"Dr.Gaynorsaid."Inhuman

anesthesiathosepatientsarenot anesthetizednearlyasdeeply becausetypicallytheyhaveamore balancedapproachtoanesthesia --usingmusclerelaxantstocause

Dr. Fred Metzger

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paralysissopatientsreallyhaveto beunconscious.Theydon'thave nearlythedegreeofhypotension wedobecausewehavetomake ourpatientsmuchdeeper." "Thepresenceofdedicated personnelandutilizationof sophisticatedmonitoringplayinto thisaswell,"Dr.Muirsaid."Monitors thatevaluatecardiovascular, respiratoryandCNSfunction areusedinmosthumanpatients thatareanesthetized."Inaddition,

theanesthetic/surgicalrequirements. Inhumanmedicinethenumberof drugsadministeredrangesbetween 7and14." Additionally,therearemanymore regulationsonthehumanside,so thereareminimummonitoring standardsrecommended bytheAmericanSocietyof Anesthesiologists,stateand localmedicalboards.Anesthesia cannotbeadministeredwithout monitoringaseriesofvariables

Dr.Carrollsaid."Theyusemore neuromuscularblockingagentsthan veterinariansdoandusemorelocal anesthetictechniquesthanwedoin generalpractice." Inaddition,manyhumansarenot premedicated.Inanadulthuman, anIVcathetermaybeplacedto givedrugstoeffectinadvance ofintubation.Thisallowsthe anesthesiologisttoputthepatient inamuchlighteranestheticstate.

The Financial Case

"A lot of us are using laser surgery, pre-anesthetic testing, pain management--I compare using sevoflurane to those technologies."

Dr. Fred Metzger, DABVP

anestheticcircuitconcentrationsof gasesandanestheticaremonitored duringinhalantanesthesia. Anotherfactorordifference betweenhumanandanimalcare isthenumberofdrugsavailable. Whilehecitedahopeintheearly 1980sthatasingledrugcouldbe developedthatproducedoptimal animalanesthesia,thisgoalhasnot beenrealized.Dr.Muirsaidthat animalsaregenerallyprescribed fewerdrugsthanhumans."Iwould saythattheaverageanimalpatient mightreceivesomewherebetween threeandfourdrugs,dependingon

thatareconsideredimportant. Mosthospitalsalsorequireafull hematologicandbloodchemical profilebeforeanesthesia.

Drugs Used

Thedrugsprescribedforboth humanandanimalpatientsare surprisinglysimilar.Mostofthe expertsonthispanelcitepropofol, isofluraneandsevofluraneas examplesofcommonlyuseddrugs, alongwithopioids. "I'vebeenexposedto sevoflurane,desflurane,propofol, fentanyl,morphineandmidazolam,"

"Alotofusareusinglaser surgery,pre-anesthetictesting,pain management--Icompareusing sevofluranetothosetechnologies. Itcostsmore,butclientswillpay forit--andit'sgoodmedicine. That'swhateveryoneisinterested inachieving." That'stheassessmentofDr.Fred Metzger,principalatMetzgerAnimal ClinicinStateCollege,PA.Hefeels thatadoptionofsevofluraneas theonlyanestheticinhispractice servesasadifferentiatorfromother veterinarypractices,butalsoasa distinctmarketingadvantage. "Whenwetalktoourclients aboutroutineprocedureslikea dental,they'reconcernedthatthe animalhastobeanesthetized," Dr.Metzgersaid."Itellthem we'reusingwhatIbelieveisasafe anesthetic,andItellthemabout sevoflurane.Iusesevofluraneto differentiateourpracticefrom others,whichIthinkisimportant. Weneedtotellourclientswhat wehavethatotherplacesdon't."

12

Anesthetics and the Veterinary Practice

Whenthetopicisveterinary anesthesia,thenumberone concernforeveryoneissafety, accordingtoDr.Metzger.Toallay thosefears,Dr.Metzgerandhis teambringitupinconsultation-- evenoninquirycalls.Whenpeople calluptotalkaboutaprocedure likespayorneutering,theMetzger stafftalksaboutsevofluraneand itsadvantages--evenifthecallis aboutpricing.TheMetzgerAnimal Clinicalsoreferencessevoflurane onitsWebsite. "Ifyou'redoingpain management,lasersurgery, pre-anesthetictestingorputtingIV cathetersorfluidsineverypatient, youshouldbeusingsevoflurane," Dr.Metzgersaid."You'redoing thosethingsbecauseit'sbetter medicine--lesspain,lessbleeding andlessswelling." There'sapragmaticsideto hisdecisiontousesevoflurane exclusively:Theentirestaffcomesto learndeepdetailsaboutapplication, monitoringandmanagementofa singleanesthetic. "Whenyoulookatveterinary medicine,whodoesouranesthesia? Wedonothaveboard-certified anesthesiologists;wehavesomeone we'vetrained,"Dr.Metzger said."Wheneverwestartusing multipleagents,isofluranefor regularpatientsandsevoflurane forhigher-riskpatients,it'shardto teachpeopletounderstandthe differences--especiallyifthey're nottrainedanesthesiologists.Ithink it'sriskyanddangerous. "I'vebeeninpracticeswhere thesevofluranevaporizerandthe isofluranevaporizerareonthe samemachine.Thereisn'tapractice thatIknowofthathasn'tmixed thetubesandhadthewrong vaporizeronthewronganimal," hesaid."Ilearnedthatit'sbetter tohaveeveryonetrainedonone agent.Wehavemoreexperience howtotrainsomeoneontwo anesthetics?Ithinkthekeyto howtomakeitmoreprofitable isinthetraining.Iknow sevofluraneismoreexpensive thanisoflurane,butitwilllet medomoreprocedures." Hecitesdentistryasanexample. Manypeopleareafraidofthe effectananestheticlikeisoflurane

"If the cost to use sevoflurane is $10, $20 or $30 more, the clients are not going to care."

Dr. Fred Metzger, DABVP

withthatagentandweknowhow tomonitorit;we'renotasking peoplewhodon'thaveformal traininginanesthesiologyto handleagivencase.Thisis someone'spet." Tocutdownonmistakesinhis procedures,Dr.Metzger'steam reliesonsafeprotocols,including pre-anesthetictesting,usingIV catheters,painmanagementsteps andusingsevoflurane.Inaddition, he'sstandardizedonasinglebrand ofmonitoringequipmentto ensureconfidence. "Iincreasedallofmycostsby 25percentwhenwewentfrom allisofluranetoallsevoflurane," Dr.Metzgersaid."Buthowmuch timewasIwastingtryingtodecide

hasontheirpetpost-operation: groggy,lethargic,tiredand lackingenergy.Theoutcomefor apostoperativesevoflurane patientmeansasmooth,quick returntonormalfunction. "Ifthecosttousesevoflurane is$10,$20or$30more,the clientsarenotgoingtocare. We'veproventhatwithlaser surgery,"Dr.Metzgersaid."How manypeoplewilldolasersurgery atanadditionalcostof$60or $80--isthatsomethingthey reallyneed?Youcandospayor neuteringwithoutthelaser,but alotofclientswilloptforthat becauseit'sbetterforthe patient.It'stheexactsamething withanesthesia."n

13

SevoFlo®

(sevoflurane)

5458

Inhalation Anesthetic For Use in Dogs Caution: Federal law restricts this drug to use by or on the order of a licensed veterinarian. DESCRIPTION: SevoFlo (sevoflurane), a volatile liquid, is a halogenated general inhalation anesthetic drug. Its chemical name is fluoromethyl 2,2,2trifluoro-l- (trifluoromethyl) ethyl ether, and its structural formula is:

Sevoflurane Physical Constants are: Molecular weight 200.05 Boiling point at 760 mm Hg 58.6°C Specific gravity at 20°C 1.520-1.525 g/mL Vapor pressure in mm Hg at 20°C 157 at 25°C 197 at 36°C 317 Distribution Partition Coefficients at 37°C: Blood/Gas 0.63-0.69 Water/Gas 0.36 Olive Oil/Gas 47-54 Brain/Gas 1.15 Mean Component/Gas Partition Coefficients at 25°C for Polymers Used Commonly in Medical Applications: Conductive rubber 14.0 Butyl rubber 7.7 Polyvinyl chloride 17.4 Polyethylene 1.3 Sevoflurane is nonflammable and nonexplosive as defined by the requirements of International Electrotechnical Commission 601-2-13. Sevoflurane is a clear, colorless, stable liquid containing no additives or chemical stabilizers. Sevoflurane is nonpungent. It is miscible with ethanol, ether, chloroform and petroleum benzene, and it is slightly soluble in water. Sevoflurane is stable when stored under normal room lighting condition according to instructions. INDICATIONS: SevoFlo is indicated for induction and maintenance of general anesthesia in dogs. DOSAGE AND ADMINISTRATION: Inspired Concentration: The delivered concentration of SevoFlo should be known. Since the depth of anesthesia may be altered easily and rapidly, only vaporizers producing predictable percentage concentrations of sevoflurane should be used. Sevoflurane should be vaporized using a precision vaporizer specifically calibrated for sevoflurane. Sevoflurane contains no stabilizer. Nothing in the drug product alters calibration or operation of these vaporizers. The administration of general anesthesia must be individualized based on the patient's response. WHEN USING SEVOFLURANE, PATIENTS SHOULD BE CONTINUOUSLY MONITORED AND FACILITIES FOR MAINTENANCE OF PATENT AIRWAY, ARTIFICIAL VENTILATION, AND OXYGEN SUPPLEMENTATION MUST BE IMMEDIATELY AVAILABLE. Replacement of Desiccated CO2 Absorbents: When a clinician suspects that the CO2 absorbent may be desiccated, it should be replaced. An exothermic reaction occurs when sevoflurane is exposed to CO2 absorbents. This reaction is increased when the CO2 absorbent becomes desiccated (see PRECAUTIONS). Premedication: No specific premedication is either indicated or contraindicated with sevoflurane. The necessity for and choice of premedication is left to the discretion of the veterinarian. Preanesthetic doses for premedicants may be lower than the label directions for their use as a single medication.1 Induction: For mask induction using sevoflurane alone, inspired concentrations up to 7% sevoflurane with oxygen are employed to induce surgical anesthesia in the healthy dog. These concentrations can be expected to produce surgical anesthesia in 3 to 14 minutes. Due to the rapid and dose dependent changes in anesthetic depth, care should be taken to prevent overdosing. Respiration must be monitored closely in the dog and supported when necessary with supplemental oxygen and/or assisted ventilation. Maintenance: SevoFlo may be used for maintenance anesthesia following mask induction using sevoflurane or following injectable induction agents. The concentration of vapor necessary to maintain anesthesia is much less than that required to induce it. Surgical levels of anesthesia in the healthy dog may be maintained with inhaled concentrations of 3.7-4.0% sevoflurane in oxygen in the absence of premedication and 3.3-3.6% in the presence of premedication. The use of injectable induction agents without premedication has little effect on the concentrations of sevoflurane required for maintenance. Anesthetic regimens that include opioid, alpha2-agonist, benzodiazepine or phenothiazine premedication will allow the use of lower sevoflurane maintenance concentrations. CONTRAINDICATIONS: SevoFlo is contraindicated in dogs with a known sensitivity to sevoflurane or other halogenated agents. WARNINGS: Sevoflurane is a profound respiratory depressant. DUE TO THE RAPID AND DOSE DEPENDENT CHANGES IN ANESTHETIC DEPTH, RESPIRATION MUST BE MONITORED CLOSELY IN THE DOG AND SUPPORTED WHEN NECESSARY WITH SUPPLEMENTAL OXYGEN AND/OR ASSISTED VENTILATION. In cases of severe cardiopulmonary depression, discontinue drug administration, ensure the existence of a patent airway and initiate assisted or controlled ventilation with pure oxygen. Cardiovascular depression should be treated with plasma expanders, pressor agents, antiarrhythmic agents or other techniques as appropriate for the observed abnormality. Due to sevoflurane's low solubility in blood, increasing the concentration may result in rapid changes in anesthetic depth and hemodynamic changes (dose dependent decreases in respiratory rate and blood pressure) compared to other volatile anesthetics. Excessive decreases in blood pressure or respiratory depression may be corrected by decreasing or discontinuing the inspired concentration of sevoflurane. Potassium hydroxide containing CO2 absorbents (e.g. BARALYME®) are not recommended for use with sevoflurane. ADVERSE REACTIONS: The most frequently reported adverse reactions during maintenance anesthesia were hypotension, followed by tachypnea, muscle tenseness, excitation, apnea, muscle fasciculations and emesis. Infrequent adverse reactions include paddling, retching, salivation, cyanosis, premature ventricular contractions and excessive cardiopulmonary depression. Transient elevations in liver function tests and white blood cell count may occur with sevoflurane, as with the use of other halogenated anesthetic agents.

PRECAUTIONS: Halogenated volatile anesthetics can react with desiccated carbon dioxide (CO2) absorbents to produce carbon monoxide (CO) that may result in elevated carboxyhemoglobin levels in some patients. To prevent this reaction, sevoflurane should not be passed through desiccated soda lime or barium hydroxide lime. Replacement of Desiccated CO2 Absorbents: When a clinician suspects that the CO2 absorbent may be desiccated, it should be replaced before administration of sevoflurane. The exothermic reaction that occurs with sevoflurane and CO2 absorbents is increased when the CO2 absorbent becomes desiccated, such as after an extended period of dry gas flow through the CO2 absorbent canisters. Extremely rare cases of spontaneous fire in the respiratory circuit of the anesthesia machine have been reported during sevoflurane use in conjunction with the use of a desiccated CO2 absorbent, specifically those containing potassium hydroxide (e.g. BARALYME). Potassium hydroxide containing CO2 absorbents are not recommended for use with sevoflurane. An unusually delayed rise in the inspired gas concentration (decreased delivery) of sevoflurane compared with the vaporizer setting may indicate excessive heating of the CO2 absorbent canister and chemical breakdown of sevoflurane. The color indicator of most CO2 absorbent may not change upon desiccation. Therefore, the lack of significant color change should not be taken as an assurance of adequate hydration. CO2 absorbents should be replaced routinely regardless of the state of the color indicator. The use of some anesthetic regimens that include sevoflurane may result in bradycardia that is reversible with anticholinergics. Studies using sevoflurane anesthetic regimens that included atropine or glycopyrrolate as premedicants showed these anticholinergics to be compatible with sevoflurane in dogs. During the induction and maintenance of anesthesia, increasing the concentration of sevoflurane produces dose dependent decreases in blood pressure and respiratory rate. Due to sevoflurane's low solubility in blood, these changes may occur more rapidly than with other volatile anesthetics. Excessive decreases in blood pressure or respiratory depression may be related to depth of anesthesia and may be corrected by decreasing the inspired concentration of sevoflurane. RESPIRATION MUST BE MONITORED CLOSELY IN THE DOG AND SUPPORTED WHEN NECESSARY WITH SUPPLEMENTAL OXYGEN AND/OR ASSISTED VENTILATION. The low solubility of sevoflurane also facilitates rapid elimination by the lungs. The use of sevoflurane in humans increases both the intensity and duration of neuromuscular blockade induced by nondepolarizing muscle relaxants. The use of sevoflurane with nondepolarizing muscle relaxants has not been evaluated in dogs. Compromised or debilitated dogs: Doses may need adjustment for geriatric or debilitated dogs. Because clinical experience in administering sevoflurane to dogs with renal, hepatic and cardiovascular insufficiency is limited, its safety in these dogs has not been established. Breeding dogs: The safety of sevoflurane in dogs used for breeding purposes, during pregnancy, or in lactating bitches, has not been evaluated. Neonates: The safety of sevoflurane in young dogs (less than 12 weeks of age) has not been evaluated. HUMAN SAFETY: Not for human use. Keep out of reach of children. Operating rooms and animal recovery areas should be provided with adequate ventilation to prevent the accumulation of anesthetic vapors. There is no specific work exposure limit established for sevoflurane. However, the National Institute for Occupational Safety and Health has recommended an 8 hour time-weighted average limit of 2 ppm for halogenated anesthetic agents in general. Direct exposure to eyes may result in mild irritation. If eye exposure occurs, flush with plenty of water for 15 minutes. Seek medical attention if irritation persists. Symptoms of human overexposure (inhalation) to sevoflurane vapors include respiratory depression, hypotension, bradycardia, shivering, nausea and headache. If these symptoms occur, remove the individual from the source of exposure and seek medical attention. The material safety data sheet (MSDS) contains more detailed occupational safety information. For customer service, adverse effects reporting, and/or a copy of the MSDS, call (888) 299-7416. CLINICAL PHARMACOLOGY: Sevoflurane is an inhalational anesthetic agent for induction and maintenance of general anesthesia. The Minimum Alveolar Concentration (MAC) of sevoflurane as determined in 18 dogs is 2.36%.2 MAC is defined as that alveolar concentration at which 50% of healthy patients fail to respond to noxious stimuli. Multiples of MAC are used as a guide for surgical levels of anesthesia, which are typically 1.3 to 1.5 times the MAC value. Because of the low solubility of sevoflurane in blood (blood/gas partition coefficient at 37°C = 0.63-0.69), a minimal amount of sevoflurane is required to be dissolved in the blood before the alveolar partial pressure is in equilibrium with the arterial partial pressure. During sevoflurane induction, there is a rapid increase in alveolar concentration toward the inspired concentration. Sevoflurane produces only modest increases in cerebral blood flow and metabolic rate, and has little or no ability to potentiate seizures.3 Sevoflurane has a variable effect on heart rate, producing increases or decreases depending on experimental conditions.4,5 Sevoflurane produces dose-dependent decreases in mean arterial pressure, cardiac output and myocardial contraction.6 Among inhalation anesthetics, sevoflurane has low arrhythmogenic potential.7 Sevoflurane is chemically stable. No discernible degradation occurs in the presence of strong acids or heat. Sevoflurane reacts through direct contact with CO2 absorbents (soda lime and barium hydroxide lime) producing pentafluoroisopropenyl fluoromethyl ether (PIFE, C4H2F6O), also known as Compound A, and trace amounts of pentafluoromethoxy isopropyl fluoromethyl ether (PMFE, C5H6F6O), also known as Compound B. Compound A: The production of degradants in the anesthesia circuit results from the extraction of the acidic proton in the presence of a strong base (potassium hydroxide and/or NaOH) forming an alkene (Compound A) from sevoflurane. Compound A is produced when sevoflurane interacts with soda lime or barium hydroxide lime. Reaction with barium hydroxide lime results in a greater production of Compound A than does reaction with soda lime. Its concentration in a circle absorber system increases with increasing sevoflurane concentrations and with decreasing fresh gas flow rates. Sevoflurane degradation in soda lime has been shown to increase with temperature. Since the reaction of carbon dioxide with absorbents is exothermic, this temperature increase will be determined by the quantities of CO2 absorbed, which in turn will depend on fresh gas flow in the anesthetic circle system, metabolic status of the patient and ventilation. Although Compound A is a dose-dependent nephrotoxin in rats, the mechanism of this renal toxicity is unknown. Two spontaneously breathing dogs under sevoflurane anesthesia showed increases in concentrations of Compound A as the oxygen flow rate was

decreased at hourly intervals, from 500 mL/min (36 and 18 ppm Compound A) to 250 mL/min (43 and 31 ppm) to 50 mL/min (61 and 48 ppm).8 Fluoride ion metabolite: Sevoflurane is metabolized to hexafluoroisopropanol (HFIP) with release of inorganic fluoride and CO2. Fluoride ion concentrations are influenced by the duration of anesthesia and the concentration of sevoflurane. Once formed, HFIP is rapidly conjugated with glucuronic acid and eliminated as a urinary metabolite. No other metabolic pathways for sevoflurane have been identified. In humans, the fluoride ion half-life was prolonged in patients with renal impairment, but human clinical trials contained no reports of toxicity associated with elevated fluoride ion levels. In a study in which 4 dogs were exposed to 4% sevoflurane for 3 hours, maximum serum fluoride concentrations of 17.0-27.0 mcmole/L were observed after 3 hours of anesthesia. Serum fluoride fell quickly after anesthesia ended, and had returned to baseline by 24 hours post-anesthesia. In a safety study, eight healthy dogs were exposed to sevoflurane for 3 hours/day, 5 days/week for 2 weeks (total 30 hours exposure) at a flow rate of 500 mL/min in a semi-closed, rebreathing system with soda lime. Renal toxicity was not observed in the study evaluation of clinical signs, hematology, serum chemistry, urinalysis, or gross or microscopic pathology. DRUG INTERACTIONS: In the clinical trial, sevoflurane was used safely in dogs that received frequently used veterinary products including steroids and heartworm and flea preventative products. Intravenous Anesthetics: Sevoflurane administration is compatible with barbiturates, propofol and other commonly used intravenous anesthetics. Benzodiazepines and Opioids: Benzodiazepines and opioids would be expected to decrease the MAC of sevoflurane in the same manner as other inhalational anesthetics. Sevoflurane is compatible with benzodiazepines and opioids as commonly used in surgical practice. Phenothiazines and Alpha2-Agonists: Sevoflurane is compatible with phenothiazines and alpha2- agonists as commonly used in surgical practice. In a laboratory study, the use of the acepromazine/oxymorphone/ thiopental/sevoflurane anesthetic regimen resulted in prolonged recoveries in eight (of 8) dogs compared to recoveries from sevoflurane alone. CLINICAL EFFECTIVENESS: The effectiveness of sevoflurane was investigated in a clinical study involving 196 dogs. Thirty dogs were mask-induced with sevoflurane using anesthetic regimens that included various premedicants. During the clinical study, one hundred sixty-six dogs received sevoflurane maintenance anesthesia as part of several anesthetic regimens that used injectable induction agents and various premedicants. The duration of anesthesia and the choice of anesthetic regimens were dependent upon the procedures that were performed. Duration of anesthesia ranged from 16 to 424 minutes among the individual dogs. Sevoflurane vaporizer concentrations during the first 30 minutes of maintenance anesthesia were similar among the various anesthetic regimens. The quality of maintenance anesthesia was considered good or excellent in 169 out of 196 dogs. The table shows the average vaporizer concentrations and oxygen flow rates during the first 30 minutes for all sevoflurane maintenance anesthesia regimens:

Average Vaporizer Concentrations among Anesthetic Regimens 3.31 - 3.63% Average Vaporizer Concentrations among Individual Dogs 1.6 - 5.1% Average Oxygen Flow Rates among Anesthetic Regimens 0.97 - 1.31 L/minute Average Oxygen Flow Rates among Individual Dogs 0.5 - 3.0 L/minute

During the clinical trial, when a barbiturate was used for induction, the times to extubation, sternal recumbency and standing recovery were longer for dogs that received anesthetic regimens containing two preanesthetics compared to regimens containing one preanesthetic. Recovery times were shorter when anesthetic regimens used sevoflurane or propofol for induction. The quality of recovery was considered good or excellent in 184 out of 196 dogs. Anesthetic regimen drug dosages, physiological responses, and the quality of induction, maintenance and recovery were comparable between 10 sighthounds and other breeds evaluated in the study. During the clinical study there was no indication of prolonged recovery times in the sighthounds. HOW SUPPLIED: SevoFlo (sevoflurane) is packaged in amber colored bottles containing 100 mL and 250 mL sevoflurane, List 5458. STORAGE CONDITIONS: Store at controlled room temperature 15°-30°C (59°-86°F). REFERENCES: 1. Plumb, D.C. ed., Veterinary Drug Handbook, Second Edition, University of Iowa Press, Ames, IA: p. 424 (1995). 2. Kazama, T. and Ikeda, K., Comparison of MAC and the rate of rise of alveolar concentration of sevoflurane with halothane and isoflurane in the dog. Anesthesiology. 68: 435-437 (1988). 3. Scheller, M.S., Nakakimura, K., Fleischer, J.E. and Zornow, M.H., Cerebral effects of sevoflurane in the dog: Comparison with isoflurane and enflurane. Brit. J. Anesthesia 65: 388-392 (1990). 4. Frink, E.J., Morgan, S.E., Coetzee, A., Conzen, P.F. and Brown, B.R., Effects of sevoflurane, halothane, enflurane and isoflurane on hepatic blood flow and oxygenation in chronically instrumented greyhound dogs. Anesthesiology 76: 85-90 (1992). 5. Kazama, T. and Ikeda, K., The comparative cardiovascular effects of sevoflurane with halothane and isoflurane. J. Anesthesiology 2: 63-8 (1988). 6. Bernard, J. M., Wouters, P.F., Doursout, M.F., Florence, B., Chelly, J.E. and Merin, R.G., Effects of sevoflurane on cardiac and coronary dynamics in chronically instrumented dogs. Anesthesiology 72: 659-662 (1990). 7. Hayaski, Y., Sumikawa, K., Tashiro, C., Yamatodani, A. and Yoshiya, I., Arrhythmogenic threshold of epinephrine during sevoflurane, enflurane and isoflurane anesthesia in dogs. Anesthesiology 69: 145-147 (1988). 8. Muir, W.W. and Gadawski, J., Cardiorespiratory effects of low-flow and closed circuit inhalation anesthesia, using sevoflurane delivered with an in-circuit vaporizer and concentrations of compound A. Amer. J. Vet. Res. 59 (5): 603-608 (1998).

SevoFlo® is a registered trademark of Abbott Laboratories. Manufactured by Abbott Laboratories, North Chicago, IL 60064, USA Product of Japan For customer service call (888) 299-7416. ©Abbott 2009 Taken from Commodity Number 03-A289/R7, SevoFlo, sevoflurane, package insert.

SEVO-151/R2 July 2010

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©2010 Abbott Laboratories

Dedicated to Future Generations

Abbott Animal Health is committed to advancing the future of veterinary science and animal health.

Abbott Animal Health is dedicated to providing a better future for animals, owners and veterinary professionals. Our exceptional research & development investment, industry sponsorships and partnerships with leading universities help to build the foundation for tomorrow's breakthroughs. Abbott's continuing education programs, comprehensive training tools, on-call expertise and technical service set the standard in the industry. Finally, our products are trusted at thousands of hospitals and clinics every day.

Abbott Animal Health is proud to offer these respected products:

· · · · · · · SevoFlo® (sevoflurane) PropoFloTM (propofol) IsoFlo® (isoflurane, USP) AlphaTRAK® Blood Glucose Monitoring System GLUture® Topical Tissue Adhesive CliniCare® Canine/Feline Liquid Diet CliniCare® R/F Feline Liquid Diet · Vectra 3DTM for the treatment and control of fleas, ticks and mosquitos · Vectra for Cats & KittensTM--controls all flea stages · Vectra for Dogs & PuppiesTM--controls all flea stages · Fluid Therapy

To learn more about Abbott Animal Health, our dedication to animal health excellence and our quality products, contact Customer Service at 888-299-7416 or visit www.AbbottAnimalHealth.com.

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SEVO-202/R2 September 2010 ©2010 Abbott Laboratories Vectra 3DTM, Vectra for Cats & KittensTM and Vectra for Dogs and PuppiesTM are registered trademarks of Summit VetPharm.

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