Paediatric Anaesthetists of Great Britain & Ireland Guidelines ... Contents Page No. Key to evidence statements and grades of recommendation 4 Introduction 5 Remit of the guideline

TheAssociationofPaediatricAnaesthetistsofGreatBritain&Ireland

ContributingAuthors:SimonMartinDavidBainesHelenHoltbyAlisonSCarr

Autumn 2016

GuidelinesonthePreventionofPost-operativeVomitinginChildren

GuidelinesonthePreventionofPostoperativeVomitinginChildrenMembersofthe2016GuidelinesRevisionGroup: DrSimonMartinConsultantPaediatricAnaesthetistPlymouthHospitalsNHSTrustDerrifordHospitalPlymouthProfessorAlisonSCarrConsultantPaediatricAnaesthetistHeadofClinicalEducation&ProfessorCollegeofMedicineQatarUniversityPOBox2713Doha,QatarDrDavidBainesClinicalAssociateProfessorHead,DepartmentofAnaesthesiaTheChildren'sHospitalatWestmeadNSWAustraliaDrHelenHoltbyStaffAnesthesiologistDivisionofCardiacAnesthesiaDepartmentofAnesthesiaandPainMedicineSickKidsHospital,Toronto

AdditionalContributingAuthorsof2009GuidelineSimonCourtman

NeilMortonScottJacobson

LiamBrennanPer-ArneLönnqvistJackiePope

3

Contents PageNo.

Keytoevidencestatementsandgradesofrecommendation 4

Introduction 5

Remitoftheguideline

Glossary 7

1.Identifyingchildrenathighriskofpostoperativevomiting(POV) 8

A.PatientfactorsAge,historyofPOV,motionsickness,gender,preoperativeanxiety,smoking

8

B.SurgicalFactorsDurationofsurgery,typeofsurgery

10

C.AnaestheticFactorsNitrousoxide,volatileagents,peri-operativeopioids,anticholinesterases,peri-operativefluids

12

2.PharmacologicaltreatmentofPOVinchildren

A.Anti-emeticsforprevention&reductionofPOVinchildren

14

SingleAgents: 14

5HT3Antagonists,Dexamethasone,Metoclopramide,Prochlorperazine,Cyclizine,Dimenhydrinate

CombinationTherapy: 24

Ondansetronanddexamethasone,Ondansetronandothercombinationanti-emetictherapy,Tropisetron

B.Anti-emeticsfortreatingestablishedPOVinchildren 25

3.Non-pharmacologicaltreatmentofPOVinchildren 27

StimulationoftheP6Acupuncturepoint

4.Summaryoffindings&recommendations 29

References 30

GuidelinesonthePreventionofPostoperativeVomitinginChildrenKeytoEvidenceStatementsandGradesandStrengthofRecommendation:

TheguidelineshavebeenpreparedusingSIGNMethodology1drawingtogetheravailableevidenceandrecommendingbestpracticebasedontheavailableevidenceandontheclinicalexperienceoftheguidelinesdevelopmentgroup.SincethepreviousGuidelinein2009,SIGNhaveimplementedtheGradesofRecommendation,Assessment,DevelopmentandEvaluation(GRADE)methodology.Inaccordancewiththis,therecommendationsforkeyareasinfluencingpracticearenowclassifiedasunconditionalorconditional.ThisStrengthofRecommendationbasedonthequalityoftheevidencereplacestheprevious‘ABCD’systemthatwasrelatedtotypesofstudy.ForreferencetheoriginalguidelineremainsavailableontheAPAGBIwebsite.

StrengthofRecommendation

Unconditional(UC) Strongevidence,noimportantdrawbacks

Conditional(C) Weakerevidence,seriouspotentialdrawbacks

5

IntroductionPostoperativeVomiting(POV)isanimportantcauseofmorbidityinchildren.ThisreportfortheAssociationofPaediatricAnaesthetistsofGreatBritain&Irelandinvestigatesthecausesofpost-operativevomitinginchildrenandsummarisestheefficacyoftreatmentsusedtopreventandtreatpostoperativevomitinginchildren.Theoriginalguidancewaspublishedin2009.TheseupdatedguidelineswerepresentedattheAssociationofPaediatricAnaesthetistsofGreatBritain&Ireland(APAGBI)AnnualScientificMeetinginMay2015.Theyhavebeenwritteningoodfaithandwillberevisedasnewinformationbecomesavailable.ShouldthereaderfindanyusefuladditionalcontentpleasecontacttheChairofthePOVGuidelinesgroupbyemailtoinformafuturerevision.

RemitoftheGuidelineTheguidelineseekstoanswerthefollowingquestions:

GuidelinesonthePreventionofPostoperativeVomitinginChildren

Glossary

NNT:Numberneededtotreat

Thenumberofpatientswhoneedtobetreatedtoreducetheexpectednumberofcasesofadefinedendpointbyone.

Meta-analysis Astatisticalmethodthatcombinestheresultsofindependenttrialstogiveapreciseestimateoftreatmenteffect.

Casecontrolstudy Astudythatcomparespatientswithanidentifiedoutcomeagainstpatientswithoutthatoutcome,andreviewingthemtoseeiftheyhadanexposureofinterest.

Cohortstudy Astudyinwhichsubjectswhohaveacertainconditionand/orreceiveaparticulartreatmentarefollowedovertimeandarecomparedwithanothergroupwhoarenotaffectedbythatcondition.

Systematicreview Areviewofrelevantliteraturefocusedonaspecificquestionthattriestoidentify,evaluateandsynthesizeallhighqualityresearchevidencerelevanttothatquestion.

Randomisedcontrolstudy

Astudywherebydifferenttreatmentsarerandomlyallocatedtostudyparticipants.Thisattemptstoensuresthatbothknownandunknownconfoundingfactorsareevenlydistributedbetweentreatmentgroups,therebyreducingerrorandbias.

Sensitivity Probabilityofapositivetestamongpatientswithadisease

Specificity Probabilityofanegativetestamongpatientswithoutadisease

Positive(negative)predictivevalue

Theratioofthetruepositives(negatives)dividedbythesumofthetruepositives(negatives)andfalsepositives(negatives).

Oddsratio Theratiooftheoddsofaneventoccurringinonegrouptotheoddsofitoccurringinanothergroup.Anoddsratioof1indicatesthattheconditionoreventunderstudyisequallylikelyinbothgroups.Itprovidesanestimate(withconfidenceinterval)fortherelationshipbetweentwobinary("yesorno")variables.

Confidenceinterval Anindicationofthereliabilityofanestimate.Theconfidencelevelwilldefinehowlikelytheintervalistocontaintheparameter.

Relativerisk Theratiooftheprobabilityofaneventoccurringinatreatmentgroupversusthecontrolgroup.

7

BackgroundPostoperativeVomiting(POV)isapproximatelytwiceasfrequentamongstchildrenasadultswithanincidenceof13-42%inallpaediatricpatients2,3.SeverePOVcanresultinarangeofcomplicationsincludingwounddehiscence,dehydrationandelectrolyteimbalanceandpulmonaryaspiration4.Itisoneoftheleadingcausesofparentaldissatisfactionaftersurgeryandistheleadingcauseofunanticipatedhospitaladmissionfollowingambulatorysurgerywithresultingincreasedhealthcarecosts5,6.Importantly,noresearchhasfocusedonthechildren’sperspectiveofPOV,andwhethertheyperceivethissymptomwiththesamedistressandloathingasadults7.IdentifyingchildrenathighriskofPOVisbeneficialasprophylacticantiemetictherapycanthenbetargetedatthisgroup.Indiscriminateprophylaxisisprobablyunnecessaryasitisfinanciallycostlyandmayresultinexcessiveadversedrugreactions8.Researchintothisimportantareaishamperedbythedifficultyindiagnosingnauseainyoungerchildren.Hence,vomitingandretchingareusedastheend-pointsinmostofthepaediatricliteratureonthissubject3.ThemainriskfactorsforPOVinchildrenmaybeconsideredinthefollowingcategories:

• Patient-relatedissues• Surgicalfactors• Anaesthetic(technique&drugsusedinperi-operativeperiod)

A.PatientFactorsAgePaediatricpatientshaveahigherincidenceofPOVcomparedtoadultswithchildrenover5yearsofagehavingarounda34-50%overallriskofvomitingaftersurgery.Thelowestincidenceoccursininfancy(5%incidenceofemesis)whilethepreschoolchildhasa20%riskofvomiting9.Inacohortstudyof1401children<14yearsold,asharpincreaseinPOVriskoccursaroundage3witha0.2-0.8%peryearincreaseinriskcontinuingintoadolescence10.Thisincreaseinriskaround3yearsofageagreeswiththefindingsofanearlierstudywhichfoundan8%incidenceofPOVinchildren<3yearsold,increasingto29%inchildren>12yearsold11.

2++,

2+

UC RiskofPOVincreasesmarkedlyabovethreeyearsoldandcontinuestorisethroughoutearlychildhoodintoadolescence.

TroublesomePOVisrareinchildrenunderthreeyearsoldandpatientsinthisage-grouprarelyrequireprophylacticantiemeticmedication.

1.IdentifyingChildrenatHighRiskofPostoperativeVomiting


HistoryofPOVThishasprovedtobeanimportantriskfactorinthemajorityofstudiesintheadultandpaediatricPOVliteratureandisincludedinalloftheriskscoringsystemstoaidpredictionofPOVthathavebeenpublishedtodate12.Aspecificpaediatriccohortstudyidentified“previousPOV”and“POVinaparentorsibling”asimportantindependentriskfactors10.Acombinedadultandpaediatricstudy(with<10%ofthestudygroupchildren)foundaprevioushistoryofPOVtobethesecondstrongestpredictorofpostoperativenauseaandvomiting13.

2++,

2-

UC AprevioushistoryofPOVisanindependentriskfactorofsubsequentPOVinchildren.

ChildrenwithapasthistoryofPOVshouldbeconsideredforprophylacticantiemeticmedication.

MotionSicknessSeveralstudiesthathavelookedatriskfactorsforPOVinchildrenmentionahistoryofmotionsickness(MS)asapotentialproblem.

Inalargeadultstudy,historyofMSwasidentifiedasastrongpredictorofPOV14howevercautionisrequiredwhenextrapolatingfromadultdata.

OnestudyinchildrenlookedspecificallyatMSasapredictorofPOV.15SeventyconsecutivechildrenwerestudiedundergoingsurgerynothighriskforPOV.

TheoverallincidenceofPOVwas29%.Fourteenchildren(20%)hadahistoryofMS;MS-positivechildrenweremorelikelytovomitthanthosewhowereMS-negative(P<0.01).Therewerenoothersignificantvariablesbetweengroups.ThesensitivityofMSasapredictorofPOVwas45%andthespecificity90%,givingapositivepredictivevalueof64.3%andanegativepredictivevalueof80.4%.ItwasconcludedthatMSwasassociatedwithPOVbutitspositivepredictivevaluewasfairlylow.

2+

C AprevioushistoryofmotionsicknessislikelytobeanindependentriskfactorofsubsequentPOVinchildren.

Childrenwithapasthistoryofmotionsicknessshouldbeconsideredforprophylacticantiemeticmedication.

Gender

FemalegenderisastrongriskfactorfrompubertyonwardsinalladultPOVstudies.Adolescentandadultfemaleshaveatwotofour-foldincreasedPOVriskwhilstprepubescentgirlslackincreasedlikelihoodofPOVcomparedtomales10,11,12,16,17.ThemarkedincreaseinPOVriskatthemenarchesuggeststhatsexhormonesareimplicated.ReportssuggestingthatPOVwasmorecommonduringthefirstweekofthemenstrualcyclehavebeenchallengedinasystematicreview18.

2+adults,

2-children

9

C Post-pubertalgirlshaveanincreasedincidenceofPOVwhichmaybesexhormonerelatedalthoughphaseofthemenstrualcycledoesnotappeartoaffecttheincidence.

Post-pubertalgirlsshouldbeconsideredforprophylacticantiemeticmedication.

PreoperativeanxietyAlthoughpreoperativeanxietyhasbeenshowntobeaweakriskfactorforPOVinadults,thiswasnotconfirmedinaprevioussmall,butwellconductedstudyinschool-agechildren19,20.

2-

ObesityEarlystudiesfromthe1950sand1960ssuggestedanassociationbetweenobesityandPOVinadults.However,asystematicreviewwithadjustmentformultipleconfoundingfactorsfailedtoconfirmtheseearlierfindings21.ThereisnocomparableevidenceregardingarelationshipbetweenobesityandPOVinchildren.

1+adults

SmokingAdultsmokersarelesssusceptibletoPOVfromconvincingdatainseveralstudies14,22,23.Nodataonthistopicarepublishedinchildren.ArecentreviewposedtheintriguingquestionifchildrenofsmokershaddecreasedPOVduetopassivesmoking4.

2+adults

B.SurgicalFactors

Durationofsurgery

TheincidenceofPOVincreaseswithlongerdurationofsurgeryandanaesthesiainbothadultandpaediatricstudies10,23.Surgeryundergeneralanaesthesiaof>30minutesdurationwasidentifiedasanindependentriskfactorinalargepaediatricstudywithanoddsratioof3.2510.HalfofthepublishedriskscoringsystemsforPOVinadultsandchildrenincludedurationofsurgeryasanimportantriskfactor17.

2++

C POVincreasessignificantlyifoperativeproceduresunderGAlastmorethan30minutes.

TypeofsurgeryThestatusoftypeofsurgeryasariskfactorforPOViscontroversial.AlthoughnumerousstudieshaveidentifiedavarietyofproceduresasbeingassociatedwithincreasedriskofPOV,thereisoftenconflictingevidencebetweenstudiesforthesameprocedure.ThisareaofPOVresearchsuffersfromtheproblemofseparating‘true’from‘surrogate’riskfactors3.Forexample,certaintypesofsurgeryassociatedwithhighpostoperativeopioidrequirementsmightbethesurrogateforincreasedPOVriskratherthantheprocedure

GuidelinesonthePreventionofPostoperativeVomitinginChildrenitself.ThishasresultedinmostoftheestablishedriskscoresforPOVnotincludinganytypeofsurgeryintheirriskmodel10.

Withtheseconsiderationsinmind,thefollowingproceduresinchildrenhavebeenassociatedwithincreasedPOVrisk:

a.Strabismussurgery

ThisisperhapsthepaediatricsurgicalprocedurethathasthestrongestevidenceofPOVriskwithahighfrequencyofemeticepisodesreportedinasystematicreview(meanincidencelatevomiting59%,butashighas87%inoneoftheincludedstudies)24.ItistheonlysurgicalprocedureincludedintheestablishedpaediatricPOVriskscorewithanoddsratioof4.33,thehighestriskfactorofthefourindependentfactorsidentifiedinthisstudy10.

1++

UC ChildrenundergoingstrabismussurgeryareathighriskofPOV.

MinimisingPOVfollowingstrabismussurgeryrequiresamultimodalapproachutilisingantiemetics,dexamethasoneandavoidingearlymobilisationintherecoveryperiod.

b.Adenotonsillectomy

Withoutantiemeticprophylaxis,ahighproportionofchildrenundergoingadenotonsillectomywillexperienceatleastoneepisodeofpostoperativevomiting(89%withoutprophylaxisinoneseries)11,25,26.However,manyofthesestudiessufferfromthedrawbackofthecompoundingeffectofperioperativeopioidadministrationthatmaybeactingasasurrogateriskfactor,asintheabsenceofopioidsinonestudyonly11%ofchildrenvomited27.

1+

UC ChildrenundergoingadenotonsillectomyareatincreasedriskofPOV.

MinimisingPOVisessentialforasuccessfulday-casetonsillectomyprogramme.Scrupuloussurgicaltechniquetodecreaseswallowedblood,avoidanceoflong-actingopioidanalgesiaandprophylacticantiemeticsanddexamethasonearekeyfactorsinachievingthisgoal.

c.Otoplasty

Otoplastyinchildrenisrecognisedforitsemeticpotentialwithanincidenceofvomitingintheabsenceofantiemeticprophylaxisof60%28.However,surgicaldressings,inparticularpackingoftheexternalearcanal,mayinfluencetheincidenceofPOVinthesepatients29.

2-

d.OtherproceduresGroinsurgery(herniotomyandorchidopexy)andpenilesurgeryhaveamodestincreasedincidenceofPOV,buttheevidenceisfromolderstudieswithnumerouscompoundingvariablessuchasopioidadministration11,16.

2-

11

TheevidencethatproceduresotherthanstrabismussurgeryandadenotonsillectomyareassociatedwithahighincidenceofPOVislesscompelling.However,whentheconsequencesofPOVmaysignificantlyaffectclinicaloutcomese.g.resultinadmissionafterday-casesurgery,considerationshouldbegiventousingprophylacticanti-emetics.

C.Anaestheticfactors

Avarietyofanaesthetic-relatedfactorshavebeenimplicatedinproducingincreasedPOVinchildren.However,fewofthesefactorsareincludedinanyofthePOVriskscoringsystemsinthepublishedliteratureforpaediatricpatients4.

Nitrousoxide

Amixedadultandpaediatricsystematicreviewconcludedthatomissionofnitrousoxidereducedtheincidenceofpostoperativevomitingbutnotnauseainhigh-riskpatientswithaNNTof5.Thereductioninemesis,byavoidingnitrousoxide,wasachievedatthecostofanincreasedriskofintraoperativeawareness30.

Inchildren,avoidingnitrousoxidehasconflictingeffectsonPOV;itproducesasmallreductioninearlyPOVfollowingdentalsurgerybutnotaftergrommetinsertionwithoutanydifferenceinlatePOVrateswitheitherprocedure31,32.InasmallRCT,therewasnodifferenceinPOVratesinpaediatricT&Aspatientswhoreceivednitrousoxidecomparedtothosewhodidnotreceivetheagent.33

1+,

2-

C TheuseofnitrousoxidedoesnotappeartobeassociatedwithahighriskofPOVinchildren

NitrousoxidemaybeusedforanaesthesiainchildrenwithoutincreasingtheincidenceofPOV.

Volatileagents

Althoughmodernvolatileagentsarelessemetogenicthanolderagents(e.g.ether),thereisevidencethatvolatileagentsmaysignificantlycontributetoearlyPOVparticularlyinhigh-riskpatients.Thereisalsoastrongdose-responserelationshipbetweenPOVanddurationofexposuretovolatileagents34.Volatileagentsarefarmoreemetogenicwhenusedformaintenanceofanaesthesiawhencomparedtopropofolmaintenanceinalargemeta-analysis35.Thereislittleevidencethatanyofthemodernagentsislessormoreemetogenicthantheothers34,35.

1++,1+

UC UseofvolatileanaestheticagentsisassociatedwithincreasedriskofemesisparticularlyinchildrenwhohaveotherriskfactorsforPOV.

ItisrecommendedthattotalintravenousanaesthesiashouldbeconsideredwhenchildrenwhoareathighriskofPOVundergosurgerythathasahighriskofproducingPOV.

GuidelinesonthePreventionofPostoperativeVomitinginChildrenPeri-operativeopioids

Despitethewidelyheldbeliefthatperi-operativeopioidadministrationisstronglyimplicatedinincreasedPOV,theevidencefromtheliteratureislesscategorical.

IntraoperativeopioiduseinchildrenintwolargestudieswasassociatedwithreducedoronlyslightincreasedincidenceofPOV10,34,whereaspostoperativeadministrationinboththesestudieswasassociatedwithincreasedPOVriskwithoddsratiosof1.64and2.3respectively.

Conversely,theuseofperioperativemorphineinchildrenisassociatedwithincreasedPOVriskforarangeofproceduresincludingadenotonsillectomy,strabismussurgeryanddentalsurgery27,36,37,38

AlthoughadministrationofperioperativeopioidsisincludedinhalfofthepublishedadultPOVriskscores,opioidusewasnotregardedasanindependent,statisticallysignificantpredictorofPOVinthemostwidelyquotedpaediatricPOVriskscoringsystem.11

1+,1-

C UseofopioidsmaybeassociatedwithincreasedriskofPOVparticularlyiflonger-actingagentsareusedinthepostoperativeperiod

TheanaesthetistshouldtrytoachievesatisfactorypostoperativeanalgesiawithouttheuseofopioidswheneverpossibleifPOVistobeminimised,particularlyinhighriskpatients.

Useofregionalandlocalanaesthesiatechniquesarerecommendedwhereappropriatetoreducetheneedforopioids.

Useofanticholinesterasedrugs

AntagonismofneuromuscularblockadehasbeenassociatedwithincreasedriskofPOV.Inasystematicreviewofthissubjectinamixedadultandpaediatricpopulation(25%children),higherdoseneostigmine(>2.5mgsinadults)wasassociatedwithasignificantlyincreasedriskofPOV,althoughthestudydidnotanalysethepaediatricandadultpatientsseparately39.

2-

C UseofanticholinesterasedrugsmayincreasePOVinchildren.

InsituationswhereachildisathighriskofPOV,anaesthesiawithoutmusclerelaxantsshouldbeconsideredtoavoidtheriskofrequiringreversalofneuromuscularblockade.

Peri-operativeFluids

Forminorsurgicalprocedures,givinglargevolumesofIVcrystalloidintraoperativelyreducedPOVinchildrenafterstrabismussurgeryinthefirst24hoursaftersurgery.40Onehundredchildrenwererandomlyassignedtoreceive30ml·kg−1·h−1(“superhydrationgroup”)or10ml·kg−1·h−1(controlgroup)ofRinger'ssolutionintra-operatively.Nauseaandvomitingoccurredin11(22%)ofpatientsinthesuperhydrationgroupand27patients(54%)ofthecontrolgroup(P=0.001).Asimilarstudyrandomised100childrenundergoingelectivetonsillectomytoeither10ml·kg−1or30ml·kg−1ofintraoperativeRinger’ssolution.41Theincidenceofpost-

1+,

13 operativevomitingat24hourswas82%inthe10ml·kg−1and62%inthe30ml·kg−1group(P=0.026).Nointra-operativeantiemeticprophylaxiswasgiventothesepatients,whichaccountsforthehighincidenceofpost-operativevomitingandlimitsthiswork’sexternalvalidity.Inastudyofchildrenadmittedfordaycasesurgery,989children(aged1month-18years)wererandomisedtotwogroups:mandatorydrinkersandelectivedrinkers.42The464mandatorydrinkershadtodemonstrateabilitytodrinkclearliquidswithoutvomitingpriortodischargewhereas525electivedrinkerschosewhethertheywishedtodrinkornotbeforedischarge.AllpatientsreceivedadequateIVfluidstosupplyacalculated8-hfluiddeficitpriortodischarge.Theincidenceofvomitingdidnotdifferbetweengroupsintheoperatingroom,thepost-anesthesiacareunitorafterdischargefromhospital.Inthedaysurgeryunit,only14%electivedrinkersvomitedcomparedto23%mandatorydrinkers(P<0.001).Themandatorydrinkersstayedlongerthanelectivedrinkersinthedaycareunit(P<0.001).Nochildrenwereadmittedtohospitalwithpersistentvomiting.

2+

1+

C Intra-operativeIVfluidsmayreducePOVinchildrenafterdaycasesurgery.

POVinchildrenmaybeincreasediftoleranceoforalfluidsismandatorybeforedischargefromdaycasesurgery.

Intra-operativefluidsmayreducePOVinchildrenafterdaycasesurgery.

Oralfluidsshouldbeofferedtochildrenwishingtodrinkbeforedischargeafterdaycasesurgerybutshouldnotbemandatory.


2.PharmacologicalTreatmentofPost-operativeVomitinginChildren

Inthissection,theevidencefortheefficacyofcommonlyusedanti-emeticsinreducingpost-operativevomitinginchildrenisreportedandrecommendationmadeforpreventingPOV.Inaddition,recommendationsaremadeontreatingestablishedPOVinchildren.

A.Anti-emeticsforPrevention&ReductionofPost-operativeVomitinginChildren

5HT3Antagonists

5HT3antagonistsareeffectiveanti-emeticsinchildren.Therearealargenumberofstudiesavailableexaminingtheincreasingnumberoftheseagentsavailableaswellassomeoftheotherissuesrelatedtoadministrationof5HT3antagonists.Ramosetronisarecentadditionwithnewevidencetosupportitsuseinchildren.OndansetronOndansetronislicensedforuseintheUKinchildrenandyoungpeople(aged2-18years)forreducingpost-operativevomitingandiscommonlyused.Theproductlicenceisforondansetron0.1mg.kg-1uptoamaximumof4mg.

WhatistheoptimaldoseofondansetronforreducingPOVinchildren?

Theefficacyofondansetronwasstudiedindoseranges0.05to0.3mg.kg-1andadoserelatedresponsewasdemonstrated43-45.TheoveralloddsratioforPOVwas0.3643.Thesummaryoddsratioper0.1mg.kg-1increaseindosewas0.43.

Subgroupanalysisofthepaediatricdata(1688children)showedthatinthepreventionofearlyvomiting,dosesof0.10and0.15mg.kg-1wereclinicallyeffectivewithNNTof4.68and2.82respectively45.Inthepreventionoflatevomiting,0.10and0.15mg.kg-1gaveNNTof5.35and3.67respectively.

Alowerdoseof0.05mg.kg-1hadanoddsratiowithconfidenceintervals0.49to11.39andwasconsiderednoteffective46.

Inchildren<24monthsgivenadoseof0.1mg.kg-1theoddsratioforreductioninemeticeventswas0.36.47Ifrequiredinpatients<6monthsadoseof0.1mg.kg-1shouldbeused.ThisdoseproducessimilarOndansetronlevelstothe0.15mg.kg-1

doseusedinolderchildren.48TheincidenceofPOVininfants<6monthsisrelativelylowhowever.

1++

UC OndansetronisaclinicallyeffectiveantiemeticinchildrenundergoingproceduresassociatedwithahighriskofPOV.Thereisadoserelatedresponsewiththeoptimaldosebeing0.15mg.kg-1.

15

ChildrenatincreasedriskofPOVshouldbegivenondansetron0.15mg.kg-1.OndansetroncanbeusedasasingleagenttopreventearlyandlatePOV.

Whatroutesofadministrationareeffectiveforondansetron?Inameta-analysisofchildrenundergoingtonsillectomy,studiesusingbothoralandintravenousondansetronwereincluded.TherewasnoevidencethatIVwasmoreeffectivethantheoralpreparationinchildrenundergoingtonsillectomy42.OneRCTof140childrenfoundoralondansetron0.15mg.kg-1reducedPOVsignificantlywhereasanoraldoseof0.075mg.kg-1wasnomoreeffectivethanplacebo49.Anoraldispersiblepreparationofondansetron4mgwaswelltoleratedbychildrenandefficacious50.

1+

UC TheoralrouteisaseffectiveastheintravenousroutefortheadministrationofondansetroninpreventingPOVinchildren.

Theoralroutemaybeconsideredanalternativerouteforondansetronadministrationinsituationswhereintravenousaccessisnotavailable.

WhenisthebesttimetoadministerondansetrontoreducePOV?

InaRCTof120children,administeringondansetron0.10mg.kg-1atthebeginningorendofsurgerymadenodifferencetoratesofearly,lateortotalPOV49.

ArecentCochranereviewofalladultandpaediatricPOVstudiesalsofoundnoevidencethattheriskofPOVdifferedingroupsgivenondansetronbeforeinduction,atinduction,intra-operativelyorpost-operatively51.

1+,1++

UC Thereisnoevidencedemonstratingabenefitoftimingondansetronadministrationinchildrenwithrespecttothetimeofsurgery.

Ondansetronmaybegivenbeforeinduction,atinduction,intra-operativelyorpost-operatively.

Howdoestheefficacyofondansetroncomparetootheranti-emeticsforreducingPOVinchildren?

Ondansetronhashighefficacywhencomparedwithotheranti-emetics.

Inameta-analysisexaminingstudiescomparingondansetronwithmetoclopramide(6studies)ordroperidol(9studies)inchildrenundergoingdifferenttypesofsurgery,thepooledoddsratioshowedondansetrontobemoreeffectivethandroperidol,OR0.49,andmetoclopramide,OR0.3345.

InasingleRCTof130children(45pergroup)ondansetronanddexamethasone(1mg.kg-1)werecomparedtoplacebo.BothondansetronanddexamethasonesignificantlyreducedtotalPOVandearlyPOVeffectively.However,inlatevomiting,ondansetrondidnotreducePOVcomparedtoplacebowhereasdexamethasonewasclinicallyeffectivecomparedtobothplaceboandtoondansetron51.

1+


InaBayesiananalysisofdifferentantiemeticregimens,asensitivityanalysistocorrectforpossiblepublicationbiaswasconducted53.Ondansetronhadagreaterrelativeriskreduction(0.55)thantheotherantagonists,Dolasetron(0.84),Granisetron(0.78)andTropisetron(0.73).Thiswasforsingleagentcomparedwithplacebo.ThisanalysisexcludedtheredactedpublicationsbyFujiietal.Ondansetronwastheonly5HT3antagonistwithasimilarrelativeriskreductionintheinitialanalysis(0.54vs0.55).ThisgivesfurtherconfidenceintheaccuracyofthepublisheddataonOndansetron.

WhateffectdoesOndansetronhaveontheQTinterval?

Atadoseof0.15mg.kg-1,OndansetronproducesclinicallyinsignificantQTintervalprolongationinhealthychildren54.InchildrenwithcongenitallongQTinterval,polymorphicventriculartachycardiafollowing0.1mg.kg-1ofOndansetronhasbeendescribed55.TheprevalenceofcongenitallongQTis1in250056.Ondansetronandother5HT3antagonistsshouldbeavoidedinchildrenwhereprolongedQTintervalisknownorsuspected.

WhateffectdoesOndansetronhaveontheefficacyofParacetamol?

Previouslyitwassuggestedthattheremaybeareductionofanalgesiceffectsofparacetamolby5HT3antagonists.57GranisetronandTropisetronhavebeenshowntoblocktheanalgesiceffectofParacetamolinclinicaltrialsofhealthyadultvolunteers.However,recentevidencehasdemonstratedasynergisticeffectbetweenOndansetronandParacetamol.Ondanestrondoesnotappeartoreducetheanalgesiceffectsofparacetamolandrecentevidencesuggestsasynergisticeffect.58

UC OndansetronismoreclinicallyeffectivethandroperidolormetoclopramideinpreventingPOVinchildren.OndansetronisequallyeffectivetodexamethasoneforearlyPOValthoughthelattermaybemoreeffectiveinreducinglatePOV.

OndansetronshouldbeconsideredasafirstlinetreatmentinchildrenwithahighriskofPOV.Combinationtherapywithasecondagentmayimproveitsefficacy(asdetailedbelow).

TropisetronTropisetronisaneffectiveanti-emeticforPOVinchildren.ItdoesnotyethaveaproductlicenseforuseinchildrenintheUK.

Twostudiesusingtropisetron0.1-0.2mg.kg-1inchildrendemonstrateanoveralloddsratioof0.15forPOVwithnocleardoserelatedresponse43.Onestudyof120childrenfoundnodifferenceinoutcomewithearlyorlateadministrationoftropisetron59.Anotherstudyexaminedtheadditionofdexamethasonetotropisetronandfoundthatoverallvomitingwasreducedfrom53%(tropisetron0.1mg.kg-1)to26%(tropisetron0.1mg.kg-1+dexamethasone0.5mg.kg-1)60.However,thisreductionwasnotdetecteduntilafter4hourspost-operatively.

1+

17

UC Tropisetronisaneffectiveanti-emeticinchildrenathighriskofPOVandthisefficacyisincreasedbytheadditionofdexamethasone.

AlthoughtropisteroniseffectiveinreducingPOVinchildren,itisnotlicensedforuseinchildren.OndansetronshouldbeusedforreducingPOVinchildren.

GranisetronThreestudiesoftheefficacyofgranisetroninchildrenundergoingtonsillectomydemonstrateanoddsratioforPOVof0.11usingadoserangeof10-80mcg.kg-1.Thereisnocleardoserelatedresponseasseenwithondansetron.43FurthermoreaCochranemeta-analysissuggeststhattheeffectofgranisetrononreducingPOVmaybeoverestimatedbythesepapers.51

1+

C Granisetronmaybeaneffectiveanti-emeticforPOVinchildren.

MoreevidenceisrequiredontheefficacyofgranisetroninreducingPOVinchildren.

DolasetronInadosefindingstudyin204childrenundergoingdaycasesurgery,dolasetron350mcg.kg-1wasaseffectiveatpreventingPOVasondansetron100mcg.kg-1.61Onestudyon150dexamethasone-pretreatedchildrenundergoingtonsillectomyshowedanoddsratioof0.25forPOVinchildrengivendolasetron.62

Acuteelectrocardiographicchangesinchildrenandadolescentsoccurverycommonlywithdolasetron.(http://emc.medicines.org.uk)ThereisevidencetosuggestthatacutechangesinQTcintervalaregreaterinchildrenthaninadults.Individualcasesofsustainedsupraventricularandventriculararrhythmias,cardiacarrestandmyocardialinfarctionhavebeenreportedinchildrenandadolescents.Theuseofdolasetroninchildrenandadolescentsunder18yearsoldiscontraindicated.

1+

UC Dolasetroniscontraindicatedforuseinchildrenandadolescentsunder18yearsold.

DolasetroniscontraindicatedforpreventionofPOVinchildren.

Ramosetron

Thisrecentadditiontothe5-HT3antagonistshasahigheraffinityandlongerdurationofactionthanOndansetron.Ameta-analysisconductedwithoutthefabricatedliteratureofFujiietal.comparedRamosetronwithOndansetronorPlaceboinadults.63TherelativeriskreductioninPOVof0.3mgofRamosetroncomparedwithPlacebowas0.48(<6hr)and0.5

GuidelinesonthePreventionofPostoperativeVomitinginChildren(6-12hr).ProphylacticRamosetron(0.3mg)wassuperiortoOndansetron(4mg)inreducingtherelativeriskofbothearly,(RR0.5)andlatePOV,(RR0.53)inadults.TherewasnodifferenceintherelativeriskreductionofPost-operativenausea.AprospectiveRCTinvestigatingtheincidenceofPOVoverchildrenreceivingaFentanylPCAfollowingorthopaedicsurgerycomparedasinglepost-opdoseofOndansetron(0.1mg/kg)withRamosetron(6mcg/kg).64Vomitingwastheprimaryoutcomemeasureat0-6hrs,6-24hrsand24-48hrpost-operatively.Ramosetronappearstobemoreeffectivethanondansetroninthe6-24hrtimeperiodatreducingvomiting.HoweverthenumberofPCAsstoppedduetovomitingwashigherintheRamosetrongroup.

Ramosetronisnotcurrentlylicensedforuseinchildren.Thepharmacokineticsneedtobeinevaluatedinchildrenanddoserangingstudiescarriedout.FurtherevidenceofRamosetron’suseinpaediatricPOVisrequiredbeforeitcanberecommendedinpreferencetoOndansetron.

DexamethasoneDexamethasonehasincreasinglybecomerecognisedasaneffectiveanti-emeticinchildrenonitsownandincombinationwith5HT3antagonists.

WhatistheoptimaldoseofdexamethasoneforreducingPOVinchildren?

ACochranedatabasereviewin2011examiningchildrenundergoingtonsillectomyconcludedthatchildrengivenasingledoseofIVdexamethasone0.15to1.0mg.kg-1

(max8-25mg)werehalfaslikelytovomitinthefirst24hoursaftertonsillectomy(RelativeRisk=0.49,95%CI0.41-0.58)65.RoutineuseofdexamethasoneinchildrenwasassociatedwithaNNTof5.Theauthorsdonotprovideadoserecommendationduetothepitfallsofsubgroupsanalysiswithinameta-analysis.

Adosefindingstudyofdexamethasone(0.25to1.0mg.kg-1)in168childrenundergoingstrabismussurgerycomparedtoplaceboidentifiednoadditionalbenefitofusingdosesgreaterthan0.25mg.kg-1.Forallgroupsstudied,therewasanNNTof2.2-2.7.Inallgroupsreceivingdexamethasonetherewasnoevidenceofsideeffectsrelatingtoincreasedbloodsugarsorincreasedwoundinfectionrates.66

Inanotherdosefindingstudy215childrenundergoingtonsillectomyweregivendexamethasone(0.05to0.5mg.kg-1)orplacebo.TherelativeriskofPOV(first24hr)wasreducedfrom0.54for0.15mg.kg-1to0.23with0.5mg.kg-1dexamethasone.67

ThreestudieshaveshownlowerdosesofdexamethasoneprovidesimilarclinicallysignificantpreventionofPOV.68-70

Onestudyin140childrenuseddexamethasone150mcg.kg-1(max8mg)andfoundanoverallreductioninPOVfrom71%to40%.68

Anotherstudycomparedlowdosedexamethasone(50mcg.kg-1to250mcg.kg-1)findingasignificantreductioninPOVevenwithdosesassmallas50mcg.kg-1.69

TheNNTrangeforallgroupswas2-2.9.

Inanotherstudy.125childrenundergoingadenotonsillectomyortonsillectomy

1+,1++

19 wereenrolledinadose-escalatingstudyofdexamethasone:0.0625,0.125,0.25,0.5,or1mg.kg-1,maximumdose24mg.70Therewasnodose-escalationresponsetodexamethasoneforpreventingvomiting,reducingpain,shorteningtimetofirstliquidintake,ortheincidenceofvoicechange.Thelowestdoseofdexamethasone(0.0625mg.kg-1)wasaseffectiveasthehighestdose(1.0mg.kg-1)forpreventingPOVorreducingtheincidenceofothersecondaryoutcomes.Theauthorsconcludethereisnojustificationfortheuseofhigh-dosedexamethasoneforthepreventionofPONVinthiscohortofchildren.

Adoseof0.5mg.kg-1wasassociatedwithasignificantlyhigherrelativeriskofpostoperativebleeding,7.42vs.1.04for0.15mg.kg-1.67Thisislikelyatype1errorduetoflawsinthistrial’smethodology.Aretrospectivecohortstudytodeterminetheassociatedriskofpostoperativebleedingin97000paediatrictonsillectomypatientsfoundasmallincreaseinbleedingrateswithdexamethasoneof3.1%vs2.7%.71Theauthorsconcludethatthebenefitsofdexamethasoneoutweighthissmallincreaseinabsoluterisk.

IVdexamethasonemaycauseperinealwarmthandshouldbeinjectedslowlyintheconsciouschild.Dexamethasonemayalsocauseinsomnolenceifgivenlateintheevening.ThereisonecasecontrolstudyinadultsevaluatingtheassociationbetweenpostoperativeinfectionandsingledoseDexamethasone(4-8mg).72Theoddsratioforpostoperativeinfectionwas3.However,theeditorialconcludesthebenefitofdexamethasoneoutweighsthis.Thereisnolong-termfollow-upstudyevaluatingeffectsofdexamethasoneontheimmunesysteminchildren.SeveralreportsofacutetumourlysissyndromehavebeendescribedafterdexamethasonehasbeengiventoasusceptiblepatientindosesusedinpreventingPOV73-75.TumourLysisSyndromeisapotentiallylethalconditionthatoccursparticularlyinhaematologicalmalignanciesaftertreatmentwithcytotoxictherapies.Dexamethasonehasinducedacutetumourlysisinpatientswithnon-Hodgkin’slymphoma73andacuteleukaemia74-75.Dexamethasoneshouldnotbeusedinpatientsatriskoftumourlysissyndrome.

UC DexamethasonegivenalonereducestheriskofPOVinchildren.ItappearstobeparticularlyeffectiveinpreventinglatePOV(>6hr).

MetoclopramideMetoclopramideindosesrangingfrom0.15mcg.kg-1to0.25mcg.kg-1hasbeenshowntoreducePOVinchildreninsomestudiesonly76-78.Overall,thereislittlesupportintheliteraturefortheuseofmetoclopramideasananti-emeticinchildrenfortheprophylaxisofpost-operativevomitinginthedosestested(usually0.25mcg.kg-1)15,44,79-83.

Theextrapyramidaleffectsassociatedwithmetoclopramidearemorecommonin

1+,1++

GuidelinesonthePreventionofPostoperativeVomitinginChildrenchildrenandhaveoccurredindosesusedtotreatpost-operativevomiting84.TheEuropeanMedicinesAgency,inresponsetoreportsofneurologicalsideeffectshasissuedrecommendationsthatmetoclopramide85:

• Iscontraindicatedinchildrenunderoneyearofage

• Isonlyindicatedassecond-linetherapyinpatientsagedbetween1yearand20years

• Totaldailydosage,especiallyforchildrenandyoungadultsshouldnotnormallyexceed0.5mg/kg,withamaximumof30mgdaily

UC Metoclopramideindosesof0.25mcg.kg-1orlessdoesnotreliablyreducePOVinchildren.Furtherdose-responsestudiesofmetoclopramidearerequiredtoseeifimprovedefficacyforpreventingPOVinchildrencanbeachievedathigherdoses.

Metoclopramideisnotareliableanti-emeticinchildrenandisnotrecommendedforreducingPOVinchildren.Theroleofmetoclopramideinthetreatmentofestablishedpost-operativevomitingrequiresfurtherinvestigation.

Prochlorperazine

Theanti-emeticeffectofprochlorperazineinchildrenhasnotbeendetermined.Side-effectshavebeenreportedwhenchildrenhavebeengivenprochlorperazine86.Thesearepredominantlyneurological,independentofdoseanddisappearedspontaneouslyafterdiscontinuationofthedrug.Impairedconsciousness,dyskinesia,pyramidalsignsandhypertonuswerethemainneurologicalmanifestations.

4

UC ThereisnoevidenceintheliteraturefortheefficacyofprochlorperazineforreducingPOVinchildren.

ProchlorperazineisnotrecommendedforpreventionofPOVinchildren.

21

Cyclizine

Cyclizineisapiperazineantihistamineavailableover-the-counterandbyprescriptionintheUK,Canada,USandAustralia.InCanadatheuseofcyclizineforpatientsunder6yearsoldisoff-label.Ithasbeenreportedasadrugwithpotentialforabuse87.Thereareonly2studiesontheuseofcyclizinefortreatingPOVinchildrenandneitherhadpositivefindings88-89.Ithasbeenconcludedthatthereisnodetectableanti-emeticeffectwithcyclizineandfurthermoretherewassignificantpainoninjection85.

1+

UC ThereiscurrentlynoevidencetosupporttheuseofcyclizineforPOVinchildreneitherforprophylaxisorfortreatment.

CyclizineisnotrecommendedforreducingPOVinchildren.

DimenhydrinateDimenhydrinateisthetheoclatesaltofdiphenhydramine.DimenhydrinateisavailableinCanada,theUSandAustraliabothover-thecounterandbyprescription.ItisnotavailableintheUK.Itcanbegivenorally,intravenouslyandasasuppository.Itwassynthesizedwiththeintentionofantagonizingthemoderatelysedativeeffectsofdiphenhydraminewiththemildlystimulanteffectsoftheophylline.Howeversedationanddrymouthandotheranti-muscarinicsideeffectsdooccur.SeriousadversereactionsappeartoberarealthoughitisaweaknessofbothpublishedRCTsandmeta-analysesthatthereislittledocumentationofsideeffects.

Twosystematicreviewsreportondimenhydrinate43,90.Inasystematicreviewandmeta-analysisofanti-emeticprophylaxisforchildrenundergoingtonsillectomy,dimenhydrinatewasnoteffectiveinthedosesstudied43.Inanothersystematicreview,theeffectivenessofdimenhydrinateforprophylaxisofpostoperativenauseaandvomitingwasreportedinbothadultsandchildren90.ThepaediatricstudieswereanalysedasasubgroupandtheNNTforchildrenwasreportedas4.76forIV/IMadministrationand3.57forrectaladministrationofasingleequivalentdoseofdimenhydrinatehowevertheconfidenceintervalsarewide(2.56-33.3and1.92-20).

InasmallRCTof100childrenundergoingreconstructivesurgeryforburns,dimenhydrinate0.5mg.kg-1wasfoundtobeasclinicallyeffectiveasondansetronbutmuchmorecosteffective91.Dimenhydrinate0.5mg.kg-1hasalsobeenshowntobeeffectiveinstrabismussurgery92.

1+,1++

C Insummary,thereisevidencetosupporttheuseofdimenhydrinateasprophylaxisinchildrenatmoderateorhighriskofpostoperativenauseaandvomitingexceptfortonsillectomy

Dimenhydrinate0.5mg.kg-1maybeusedtoreducePOVinchildrenexceptforchildrenundergoingtonsillectomy.

GuidelinesonthePreventionofPostoperativeVomitinginChildrenTherearenostudiesexaminingtheuseofdimenhydrinatetotreatpostoperativevomitingbutnonethelessitiscitedasrescuetherapyinonereviewarticleonperi-operativenauseaandvomitinginchildren93.

4

C DimenhydrinatehasbeenusedforrescuetherapyinestablishedPOVinchildren.

DimenhydrinatemaybeusefulforrescuetherapyinestablishedPOVinchildren.

DroperidolThisdrughasbeenusedasanantipsychoticandanti-emeticdrugforseveraldecades.ItisadopaminergicandGABAreceptorantagonist.Ithassedativeeffects,prolongstheQtintervalandisknowntocauseextra-pyramidalsymptomsonoccasion.Theselatterissueshavemeantthatthedrughasnotbeenwidelyused,especiallyintheUS,wheretheFDAissueda“blackboxwarning”aboutarrhythmiasin2001.Thiswascontroversial,andisgenerallyfelttobeunfounded.Astudyinchildrenshowedthatbothdroperidolandondansetron,inclinicallyrelevantdoses(andincombination)showedtransientincreasesinQtcinterval,butnotstatisticallydifferentfromplacebo.54ItisalsoclearthatQtcisapoorpredictorofthelikelihoodoftoursadesdepointes,eveninsomesymptomaticpatients.HoweverarrhythmiashavebeenreportedinpatientswithlongQTsyndromewhohavereceivedondansetronordroperidol.

Droperidolisaneffectiveanti-emeticandrelievesnauseasinglyandincombination.Itcanbeusedbothasprophylaxisandasrescuetherapy.AsystematicreviewspecificallyincludingpaediatrictrialsconcludedthattheNNTwas4.2atadoseof75mcg.kg-1,andthattheNNHforextrapyramidalsymptomswas91forchildren94.Droperidolwasconsistentlymoreeffectiveincontrollingnauseathanvomiting.Thedosingrecommendationsgenerallyfavourlowerdosesthan75mcg.kg-1.

Theuseofdroperidolisgenerallyconfinedtorescuetherapy,ratherthanprophylaxisbecauseoftheconcernsaroundsedation,extrapyramidalsideeffects(althoughtheyareinfrequentanddoserelated),andtheFDAwarnings.Howeveritisaninexpensive,effectivemedicationforbothprophylaxisandtreatmentofbothnauseaandvomiting,andshouldcertainlybeconsideredinpatientsinwhomdexamethasoneiscontra-indicated.

1+

C Droperidol25mcg.kg-1canbeeffectiveforbothprophylaxisandtreatmentofPOV.

ThereisconditionalevidencetosupporttheuseofdroperidolforbothprophylaxisandtreatmentofPOV,asaseconddrug,particularlyinsituationswheredexamethasoneiscontra-indicated.Theuseofdroperidoliscontra-indicatedinpatientswithknownLongQTsyndrome

23

CombinationTherapy:OndansetronandDexamethasone

ThreerandomizedcontrolstudieshaveexaminedtheefficacyofondansetroncombinedwithdexamethasoneforpreventionofPOV95-97.

Twolargestudiesdemonstratedthatondansetron50mcg.kg-1combinedwithdexamethasone150mcg.kg-1wasmoreeffectiveatpreventingPOVinchildrenundergoingstrabismussurgerythanondansetron150mcg.kg-1aloneordexamethasone150mcg.kg-1alone95,96.Astudyof193childrenundergoingstrabismussurgerycompareddexamethasone(150mcg.kg-1)alonetodexamethasone(150mcg.kg-1)plusondansetron(50mcg.kg-1)95.Theadditionofondansetronreducedoverallvomitingfrom23%to5%.Astudyof200childrenundergoingstrabismussurgerycomparedondansetron(150mcg.kg-1,maximumdose8mg)alonetodexamethasone(150mcg.kg-1)plusondansetron(50mcg.kg-1)96.TheincidenceofPOVwassignificantlylessinthecombinationgroup(9%)thanintheondansetrononlygroup(28%).

Inanotherstudynodifferencebetweentreatmentswasdetectedbetweenseveralcombinationtreatmentgroupscontainingondansetronandarangeofdexamethasonedosesandplacebo84.Thiswasattributedtotheparticularlylowbaselineincidenceofvomitingintheplacebogroup.

1+

UC OndansetroncombinedwithdexamethasoneincreasestheeffectivenessinpreventingPOVinchildren.

InchildrenathighriskofPOV,combinationtherapyofondansetronanddexamethasoneshouldbegiven.IVOndansetron150mcg.kg-1andIVdexamethasone150mcg.kg-1shouldbegiventochildrenscheduledforadenotonsillectomyorstrabismussurgery.

OndansetronandDroperidol

Thecombinationofdroperidolplusondansetronmaybesynergistic,ashasbeenshowninadults,andinastudyofchildrenundergoingstrabismusrepair98.

Ameta-analysisexamininganti-emeticcombinationtherapyincluded8paediatricstudies99.Althoughnoseparatedataoranalysiswaspresented,ondansetroncombinedwithdroperidolordexamethasonewasmoreeffectiveinpreventingPOVthanondansetronalone.ABayesianmeta-analysisofriskreductionintheprophylaxisofpaediatricPONVderivedan80%riskreductioninchildrenathighriskwhengivenondansetronplusdroperidol53.Thefindingsweresimilarusingacombinationofondansetronplusdexamethasone.

1+


C InchildrenathighriskofPOVunabletoreceivedexamethasoneconsiderprophylacticallyIVondansetron150mcg.kg-1andIVdroperidol25mcg.kg-1

Combinationanti-emetictherapyshouldbeusedforchildrenathighriskofPOVorwheresingleagenttherapyhasfailedpreviously.Ondansetronanddexamethasoneisthemosteffectivecombinationofanti-emeticsforreducingPOVinchildrenandisrecommendedforsituationsathighriskofPOV.

TropisetronandDexamethasone

Inastudyof132children,tropisetron0.1mg.kg-1alonewascomparedtotropisetron0.1mg.kg-1withdexamethasone0.5mg.kg-1forpreventionofPOVaftertonsillectomy86.AdditionofdexamethasonereducedtheoverallincidenceofPOVfrom53%to26%.Thisreductionwasnotevidentatlessthan4hours.

1+,1++

UC Tropisetronplusdexamethasoneismoreeffectivethantropisetronaloneforthepreventionofpostoperativenauseaandvomitinginchildrenundergoingtonsillectomy.

AlthoughIVtropisetronandIVdexamethasoneiseffectiveinreducingPOVinchildren,tropisetronisnotlicensedforuseinchildren.OndansetronanddexamethasoneshouldbeusedforreducingPOVinchildrenathighriskofPOV.

25

B.Anti-emeticsforTreatingEstablishedPost-operativeVomitinginChildren

Therearefewtrialsofefficacyofanti-emeticsincontrollingestablishedPOVintherecoveryroominadultsandevenfewerinchildren101,comparedtothemultitudeoftrialsonprophylaxisofPOV.

Thereisonlyonetrialofasingledoseofondansetron(0.1mg.kg-1)versusplaceboformanagingestablishedPOVinchildrenwhohavenotreceivedprophylactictherapy102:childrenexperiencingtwoemeticepisodeswithin2hofdiscontinuinganaesthesiaweregivenIVondansetron0.1mg.kg-1upto4mg(n=192)orplacebo(n=183).Theproportionofchildrenwithnoemeticepisodesandnouseofrescuemedicationwassignificantlygreater(P<0.001)intheondansetrongroupcomparedwithplaceboforboth2-and24-hperiodsafterstudydrugadministration(78%oftheondansetrongroupand34%oftheplacebogroupfor2h;53%oftheondansetrongroupand17%oftheplacebogroupfor24h).Conclusionswereasingledoseofondansetron(0.1mg.kg-1upto4mg)iseffectiveandwelltoleratedinthepreventionoffurtherepisodesofpostoperativeemesisinchildrenafteroutpatientsurgery.

Doserangingstudiesofasingledrugandcomparativestudiesofdifferentdrugsareabsentinthispatientpopulationinthesecircumstances.

Animportantstudyof428patientswhodevelopedPOVdespiteprophylaxiswithondansetron4mgIVdemonstratedthatgivingaseconddoseofondansetronwasaseffectiveasgivingplacebo103.Ifprophylaxiswithonedrugfails,aseconddrugfromanotherclassshouldbeusedforrescue.

1+

1+

C IVOndansetronmaybeeffectivefortreatingestablishedPOVinchildrenwhohavenotalreadyreceivedondansetron.

OndansetronisunlikelytobeeffectiveforestablishedPOVoccurringafterondansetronhasbeenadministered.

IVOndansetron0.15mg.kg-1shouldbeusedtotreatestablishedPOVinchildrenwhohavenotalreadyreceivedondansetron.

Forchildrenwhohavealreadybeengivenondansetronprophylactically,itisrecommendedthatasecondantiemeticfromanotherclassshouldbegiven,suchasIVdexamethasone0.15mg.kg-1orIVdroperidol25mcg.kg-1injectedslowly.


3.Non-PharmacologicalTreatmentofPost-operativeVomitinginChildren

Avarietyofdifferentnon-pharmacologicaloptionshavebeendescribedinordertopreventortreatPONVinchildrenbutthenumberofpublicationsaswellaspatientnumbersandstudydesignareofteninsufficienttoallowforameta-analysisorstructuredreview(i.e.typeofbandagingfollowingbat-earsurgery104).Thus,thissectionwillonlyfocusonthedifferenttypesofstimulationoftheP6acupuncturepoint(acupuncture,acupressure,orelectrical/laserstimulation)thathasbeenreportedinchildren.

StimulationoftheP6AcupuncturePointAmeta-analysisin1999concludedvarioustypesofacustimulationinadultswereequallyeffectivecomparedtoanti-emeticdrugsinpreventingvomitingaftersurgeryandthatsuchnon-pharmacologicalternativesweremoreeffectivethanplaceboinpreventingPONVintheearlypostoperativeperiod105.Nobenefitwasfoundwithinthepaediatricpopulationinthisreview.

Sincethentwofurtherreviewshavebeenpublishedthatincorporatemorerecentpublicationswithinthisfield.InalargeCochranereportfrom2004(up-dateofthe1999meta-analysisabove,26trials,n=3,347)106acustimulationwasagainfoundtobeofbenefitinadultscomparedtocontrol.InthisCochranereport,acustimulationwasalsofoundtobeofbenefitinchildreninreducingtheincidenceofnauseaandalsopointingtoaborderlinesignificantreductioninvomitingcomparedtoshamtreatment.Whencomparedtoanti-emeticdrugsusedforpreventionofPOV,acustimulationappearedtobeequallyeffective.

Ameta-analysisfocusingonchildrenincludedtwelveRCTs,mainlyperformedinthecontextofhigh-risksurgery(e.g.adenotonsillectomyorstrabismussurgery)107.Themeta-analysisshowedthatallacustimulationmodalitiesreducedvomiting(RR=0.69,95%CI:0.59-0.80,p<0.0001)andnausea(RR=0.59,95%CI:0.46-0.76,p<0.0001)comparedtonon-activecontrol.Inthreetrialswhereacustimulationhadbeencomparedtoanti-emeticdrugstherewasnodifferenceinreducingvomitingbetweengroups(RR=1.25,95%CI:0.54-2.3,p=0.60).Comparingthedifferentmodalities,acupuncturewasfoundmoreeffectivecomparedtoacupressureandelectricalstimulation.

1+,1++

UC CurrentevidencebasesupportsacustimulationreducingPOVcomparedtothenon-activecontrolsituation.AcustimulationappearstobeequallyeffectiveinpreventingPOVasanti-emeticdrugsinchildren.

Theuseofacustimulationcanbeconsideredasanalternativetreatmenttoanti-emeticmedicationsforsurgerywherethereisahigh-riskPOVinchildren.

27

4.SummaryofFindings&Recommendations

PatientFactorsassociatedwithahighriskofPOV:

UC RiskofPOVincreases>3yearsoldandcontinuestorisethroughoutearlychildhoodintoadolescence.

UC AprevioushistoryofPOVisanindependentriskfactorofsubsequentPOVinchildren.

C AprevioushistoryofmotionsicknessislikelytobeanindependentriskfactorofsubsequentPOVinchildren.

C Post-pubertalgirlshaveanincreasedincidenceofPOV

SurgicalproceduresassociatedwithahighriskofPOV:

UC ChildrenundergoingstrabismussurgeryareathighriskofPOV.

UC Tonsillectomy+/-Adenoidectomy

C Surgicalprocedures>30minutesduration

ChildrenatHighRiskofPOV

SurgicalproceduresassociatedwithhighriskofPOV

StrengthofRecommendation

Unconditional(UC) Strongevidence,noimportantdrawbacks

Conditional(C) Weakerevidence,seriouspotentialdrawbacks


UC UseofvolatileanaestheticagentsisassociatedwithincreasedriskofemesisparticularlyinchildrenwhohaveotherriskfactorsforPOV.

C TheuseofnitrousoxidedoesnotappeartobeassociatedwithahighriskofPOVinchildren

C UseofopioidsmaybeassociatedwithincreasedriskofPOVparticularlyiflonger-actingagentsareusedinthepostoperativeperiod.

C UseofanticholinesterasedrugsmayincreasePOVinchildren.

C Intra-operativeIVfluidsmayreducePOVinchildrenafterdaycasesurgery.

POVinchildrenmaybeincreasediftoleranceoforalfluidsismandatorybeforedischargefromdaycasesurgery.

SummaryofrecommendationsforpreventionofPOVinchildren:

UC ChildrenatincreasedriskofPOVshouldbegivenIVondansetron0.15mg.kg-1

prophylactically

UC ChildrenathighriskofPOVshouldbegivenprophylacticallyIVondansetron0.150.15mg.kg-1andIVdexamethasone0.15mg.kg-1

C InchildrenathighriskofPOVunabletoreceivedexamethasoneconsiderprophylacticallyIVondansetron0.15mg.kg-1andIVdroperidol0.025mg.kg-1

C ConsiderintravenousanaesthesiaandalternativestoopioidanalgesiainchildrenathighriskofPOV

SummaryofrecommendationsfortreatmentofestablishedPOVinchildren:

UC IVondansetron0.15mg.kg-1shouldbegiventochildrenwhohavenotalreadybeengivenondansetronforprophylaxisofPOV

C Forchildrenwhohavealreadybeengivenondansetronasecondantiemeticfromanotherclassshouldbegiven,suchas:

IVdexamethasone0.15mg.kg-1injectedslowlyorIVdroperidol0.025mg.kg-1

AnaestheticfactorsaffectingPOVinchildren

RecommendationsforPreventionofPOVinchildren

TreatmentofEstablishedPOVinchildren

29

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Documents

Paediatric Anaesthetists of Great Britain & Ireland Guidelines ... Contents Page No. Key to evidence statements and grades of recommendation 4 Introduction 5 Remit of the guideline