Guidelines on the Prevention of Postoperative Vomiting in Children

TheAssociationofPaediatricAnaesthetistsofGreatBritain&Ireland

ContributingAuthors:AlisonSCarrSimonCourtmanHelenHoltbyNeilMortonScottJacobson

LiamBrennanDavidBainesPer‐ArneLönnqvistJackiePope

Spring 2009

GuidelinesonthePreventionofPost‐operativeVomitinginChildren

GuidelinesonthePreventionofPostoperativeVomitinginChildren

ContributingAuthors/MembersoftheGuidelinesGroup: DrAlisonSCarr(Chair)ConsultantPaediatricAnaesthetistPlymouthHospitalsNHSTrustDerrifordHospitalPlymouthPL68DH

HonorarySeniorLecturerPeninsulaCollegeofMedicineandDentistryPlymouthalison.carr@pms.ac.ukDrLiamBrennanConsultantPaediatricAnaesthetistAddenbrookesHospitalCambridgeUniversityHospitalsNHSFoundationTrustHillsRdCambridgeCB20QQDrSimonCourtmanConsultantPaediatricAnaesthetistPlymouthHospitalsNHSTrustDerrifordHospitalPlymouthPL68DHDrDavidBainesClinicalAssociateProfessorHead,DeptofAnaesthesiaTheChildren'sHospitalatWestmeadNSWAustraliaDrHelenHoltbyDirectorofCardiovascularAnaesthesiaHospitalforSickChildrenTorontoCanadaProfessorPer‐ArneLönnqvistSeniorConsultantPaediatricAnaesthesia&IntensiveCareAstridLindgrensChildren’sHospitalKarolinskaUniversityHospitalStockholm,Sweden

ProfesssorDeptofPhysiologyandPharmacologyKarolinskaInstitute17177Stockholm

3 DrNeilMortonConsultantPaediatricAnaesthetistYorkhillChildren’sHospitalGlasgowSeniorLecturerUniversityofGlasgowMsJackiePopePharmacistPlymouthHospitalsNHSTrustDerrifordHospitalPlymouthPL68DHDrScottJacobsonResidentFamilyMedicine,UniversityofNevada,UnitedStatesofAmericaFormerlyClinicalFellowTheHospitalforSickChildrenTorontoCanada

GuidelinesonthePreventionofPostoperativeVomitinginChildrenWewouldliketothankthefollowingpeoplewhoprovidedfeedbackonthedraftguidelinescirculatedtoAPAmembersandlinkmeninFebruary2008:

KarenBartholomew FelicyHoward JanePeutrell

GrahamBell IanJenkins PatrickRadford

BobBingham TrottieKirwan JohnRutherford

EdCarver RosLawson JudithShort

PeterCrean JerryLuntley DavidSteward

MarcDavison RobertLoveridge MarkThomas

ClaudeEcoffey DianaMathioudakis FrancisVeyckemans

ThomasEngelhardt AndyMatthews MadeleineWang

StephenGilbert ReginaMilaszkiewicz KathyWilkinson

JohnGoddard EuniceMorley SimonWhyte

WilliamHinton PeterMurphy AmberYoung

JosefHolzki NigelPereira

5

Contents PageNo.

Keytoevidencestatementsandgradesofrecommendation 6

Introduction 7

Remitoftheguideline

Glossary 8

1.Identifyingchildrenathighriskofpostoperativevomiting(POV) 9

Background 9

A.Patientfactors

Age,historyofPOV,motionsickness,gender,preoperativeanxiety,smoking

9

B.SurgicalFactors

Durationofsurgery,typeofsurgery11

C.AnaestheticFactors

Nitrousoxide,volatileagents,peri‐operativeopioids,anticholinesterases,peri‐operativefluids

13

2.PharmacologicaltreatmentofPOVinchildren

A.Anti‐emeticsforprevention&reductionofPOVinchildren

16

SingleAgents: 16

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

CombinationTherapy: 22

Ondansetronanddexamethasone,Ondansetronandothercombinationanti‐emetictherapy,Tropisetron

B.Anti‐emeticsfortreatingestablishedPOVinchildren 24

3.Non‐pharmacologicaltreatmentofPOVinchildren 25

StimulationoftheP6Acupuncturepoint

4.Summaryoffindings&recommendations 26

References 29

GuidelinesonthePreventionofPostoperativeVomitinginChildrenKeytoEvidenceStatementsandGradesofRecommendation:

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IntroductionPostoperativeVomiting(POV)isanimportantcauseofmorbidityinchildren.ThisreportfortheAssociationofPaediatricAnaesthetistsofGreatBritain&Irelandinvestigatesthecausesofpost‐operativevomitinginchildrenandsummarisestheefficacyoftreatmentsusedtopreventandtreatpostoperativevomitinginchildren.TheguidelineshavebeenpreparedusingSIGNMethodology1drawingtogetheravailableevidenceandrecommendingbestpracticebasedontheavailableevidenceandontheclinicalexperienceoftheguidelinesdevelopmentgroup.

RemitoftheGuidelineTheguidelineseekstoanswerthefollowingquestions:

DraftguidelinesweredistributedtoAPAmembersandLinkmeninFebruary2008forfeedbackandweremadeavailableonthewebsiteoftheAssociationofPaediatricAnaesthetistsofGreatBritain&Irelandforcomment.Theseguidelinesarenowinthefinalversion.Theyhavebeenwritteningoodfaithandwillberevisedasnewinformationbecomesavailable.ShouldthereaderfindanyusefuladditionalcontentpleasecontacttheChairofthePOVGuidelinesgroupbyemailtoinformafuturerevision.

GuidelinesonthePreventionofPostoperativeVomitinginChildren

GlossaryNNT: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.

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1.IdentifyingChildrenatHighRiskofPostoperativeVomiting

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.PatientFactorsAge

PaediatricpatientshaveahigherincidenceofPOVcomparedtoadultswithchildrenover5yearsofagehavingarounda34‐50%overallriskofvomitingaftersurgery.Thelowestincidenceoccursininfancy(5%incidenceofemesis)whilethepreschoolchildhasa20%riskofvomiting9.Inacohortstudyof1401children<14yearsold,asharpincreaseinPOVriskoccursaroundage3witha0.2‐0.8%peryearincreaseinriskcontinuingintoadolescence10.Thisincreaseinriskaround3yearsofageagreeswiththefindingsofanearlierstudywhichfoundan8%incidenceofPOVinchildren<3yearsold,increasingto29%inchildren>12yearsold11.

2++,

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B RiskofPOVincreasesmarkedlyabovethreeyearsoldandcontinuestorisethroughoutearlychildhoodintoadolescence.

TroublesomePOVisrareinchildrenunderthreeyearsoldandpatientsinthisage‐grouprarelyrequireprophylacticantiemeticmedication.

GuidelinesonthePreventionofPostoperativeVomitinginChildren

HistoryofPOV

ThishasprovedtobeanimportantriskfactorinthemajorityofstudiesintheadultandpaediatricPOVliteratureandisincludedinalloftheriskscoringsystemstoaidpredictionofPOVthathavebeenpublishedtodate12.Aspecificpaediatriccohortstudyidentified“previousPOV”and“POVinaparentorsibling”asimportantindependentriskfactors10.Acombinedadultandpaediatricstudy(with<10%ofthestudygroupchildren)foundaprevioushistoryofPOVtobethesecondstrongestpredictorofpostoperativenauseaandvomiting13.

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2‐

B AprevioushistoryofPOVisanindependentriskfactorofsubsequentPOVinchildren.

ChildrenwithapasthistoryofPOVshouldbeconsideredforprophylacticantiemeticmedication.

MotionSickness

SeveralstudiesthathavelookedatriskfactorsforPOVinchildrenmentionahistoryofmotionsickness(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.However,initialreportssuggestingthatPOVwasmorecommonduringthefirstweekofthemenstrualcyclehavebeenchallengedinasystematicreview18.

2+adults,

2‐children

D Post‐pubertalgirlshaveanincreasedincidenceofPOVwhichmaybesexhormonerelatedalthoughphaseofthemenstrualcycledoesnotappeartoaffecttheincidence.

11

Post‐pubertalgirlsshouldbeconsideredforprophylacticantiemeticmedication.

Preoperativeanxiety

AlthoughpreoperativeanxietyhasbeenshowntobeaweakriskfactorforPOVinadults,thiswasnotconfirmedinaprevioussmall,butwellconductedstudyinschool‐agechildren19,20.

2‐

Obesity

Earlystudiesfromthe1950sand1960ssuggestedanassociationbetweenobesityandPOVinadults.However,asystematicreviewwithadjustmentformultipleconfoundingfactorsfailedtoconfirmtheseearlierfindings21.ThereisnocomparableevidenceregardingarelationshipbetweenobesityandPOVinchildren.

1+adults

Smoking

AdultsmokersarelesssusceptibletoPOVfromconvincingdatainseveralstudies14,22,23.Nodataonthistopicarepublishedinchildren.ArecentreviewposedtheintriguingquestionifchildrenofsmokershaddecreasedPOVduetopassivesmoking4.

2+adults

B.SurgicalFactors

Durationofsurgery

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

2++

C POVincreasessignificantlyifoperativeproceduresunderGAlastmorethan30minutes.

Typeofsurgery

ThestatusoftypeofsurgeryasariskfactorforPOViscontroversial.AlthoughnumerousstudieshaveidentifiedavarietyofproceduresasbeingassociatedwithincreasedriskofPOV,thereisoftenconflictingevidencebetweenstudiesforthesameprocedure.ThisareaofPOVresearchsuffersfromtheproblemofseparating‘true’from‘surrogate’riskfactors3.Forexample,certaintypesofsurgeryassociatedwithhighpostoperativeopioidrequirementsmightbethesurrogateforincreasedPOVriskratherthantheprocedureitself.ThishasresultedinmostoftheestablishedriskscoresforPOVnotincludinganytypeofsurgeryintheirriskmodel10.

GuidelinesonthePreventionofPostoperativeVomitinginChildrenWiththeseconsiderationsinmind,thefollowingproceduresinchildrenhavebeenassociatedwithincreasedPOVrisk:

a.Strabismussurgery

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

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A ChildrenundergoingstrabismussurgeryareathighriskofPOV.

MinimisingPOVfollowingstrabismussurgeryrequiresamultimodalapproachutilisingantiemetics,dexamethasoneandavoidingearlymobilisationintherecoveryperiod.

b.Adenotonsillectomy

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

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A ChildrenundergoingadenotonsillectomyareatincreasedriskofPOV.

MinimisingPOVisessentialforasuccessfulday‐casetonsillectomyprogramme.Scrupuloussurgicaltechniquetodecreaseswallowedblood,avoidanceoflong‐actingopioidanalgesiaandprophylacticantiemeticsanddexamethasonearekeyfactorsinachievingthisgoal.

c.Otoplasty

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

2‐

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

2‐

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

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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+

A UseofvolatileanaestheticagentsisassociatedwithincreasedriskofemesisparticularlyinchildrenwhohaveotherriskfactorsforPOV.

ItisrecommendedthattotalintravenousanaesthesiashouldbeconsideredwhenchildrenwhoareathighriskofPOVundergosurgerythathasahighriskofproducingPOV.

Peri‐operativeopioids

Despitethewidelyheldbeliefthatperi‐operativeopioidadministrationisstronglyimplicatedinincreasedPOV,theevidencefromtheliteratureislesscategorical.

IntraoperativeopioiduseinchildrenintwolargestudieswasassociatedwithreducedoronlyslightincreasedincidenceofPOV10,34,whereaspostoperativeadministrationinboththesestudieswasassociatedwithincreasedPOVriskwith

1+,1‐

GuidelinesonthePreventionofPostoperativeVomitinginChildrenoddsratiosof1.64and2.3respectively.

Conversely,theuseofperioperativemorphineinchildrenisassociatedwithincreasedPOVriskforarangeofproceduresincludingadenotonsillectomy,strabismussurgeryanddentalsurgery27,36,37,38

AlthoughadministrationofperioperativeopioidsisincludedinhalfofthepublishedadultPOVriskscores,opioidusewasnotregardedasanindependent,statisticallysignificantpredictorofPOVinthemostwidelyquotedpaediatricPOVriskscoringsystem.11

B UseofopioidsmaybeassociatedwithincreasedriskofPOVparticularlyiflonger‐actingagentsareusedinthepostoperativeperiod

TheanaesthetistshouldtrytoachievesatisfactorypostoperativeanalgesiawithouttheuseofopioidswheneverpossibleifPOVistobeminimised,particularlyinhighriskpatients.

Useofregionalandlocalanaesthesiatechniquesarerecommendedwhereappropriatetoreducetheneedforopioids.

Useofanticholinesterasedrugs

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

2‐

D UseofanticholinesterasedrugsmayincreasePOVinchildren.

InsituationswhereachildisathighriskofPOV,anaesthesiawithoutmusclerelaxantsshouldbeconsideredtoavoidtheriskofrequiringreversalofneuromuscularblockade.

Peri‐operativeFluids

Forminorsurgicalprocedures,givinglargevolumesofIVcrystalloidintraoperativelyreducedPOVinchildrenafterstrabismussurgeryinthefirst24hoursaftersurgery.40Onehundredchildrenwererandomlyassignedtoreceive30ml∙kg−1∙h−1(“superhydrationgroup”)or10ml∙kg−1∙h−1(controlgroup)oflactatedRinger'ssolutionintra‐operatively.Nauseaandvomitingoccurredin11(22%)ofpatientsinthesuperhydrationgroupand27patients(54%)ofthecontrolgroup(P=0.001).Inastudyofchildrenadmittedfordaycasesurgery,989children(aged1month‐18years)wererandomisedtotwogroups:mandatorydrinkersandelectivedrinkers.41The464mandatorydrinkershadtodemonstrateabilitytodrinkclearliquidswithoutvomitingpriortodischargewhereas525electivedrinkerschosewhethertheywishedtodrinkornotbeforedischarge.AllpatientsreceivedadequateIVfluidstosupplyacalculated8‐hfluiddeficitpriortodischarge.Theincidenceofvomitingdidnotdifferbetweengroupsintheoperatingroom,thepost‐anesthesiacareunitorafterdischargefromhospital.Inthedaysurgeryunit,

1+,

2+

15 only14%electivedrinkersvomitedcomparedto23%mandatorydrinkers(P<0.001).Themandatorydrinkersstayedlongerthanelectivedrinkersinthedaycareunit(P<0.001).Nochildrenwereadmittedtohospitalwithpersistentvomiting.

Thereisalsoevidencethatwithholdingoralfluidsfromchildrenpost‐operativelyreducedtheincidenceofvomitinginhospitalafterdaycasesurgery.42Inastudyof317children,overallPOVwasreducedfrom56%to38%(P=0.004)bywithholdingoralfluids:Althoughin‐hospitalvomitingwasreducedfrom38%to21%(P=0.003),therewasnosignificantreductioninpost‐dischargevomiting.

1+

B Peri‐operativeIVfluidsmayreducePOVinchildrenafterdaycasesurgery.

POVinchildrenmaybeincreasediftoleranceoforalfluidsismandatorybeforedischargefromdaycasesurgery.

Intra‐operativefluidsmayreducePOVinchildrenafterdaycasesurgery.

Oralfluidsshouldbeofferedtochildrenwishingtodrinkbeforedischargeafterdaycasesurgerybutshouldnotbemandatory.

GuidelinesonthePreventionofPostoperativeVomitinginChildren

2.PharmacologicalTreatmentofPost‐operativeVomitinginChildren

Inthissection,theevidencefortheefficacyofcommonlyusedanti‐emeticsinreducingpost‐operativevomitinginchildrenisreportedandrecommendationmadeforpreventingPOVinchildren.InadditionrecommendationsaremadeontreatingestablishedPOVinchildren.

A.Anti‐emeticsforPrevention&ReductionofPost‐operativeVomitinginChildren

5HT3Antagonists

5HT3antagonistsareeffectiveanti‐emeticsinchildren.Therearealargenumberofstudiesavailableexaminingtheincreasingnumberoftheseagentsavailableaswellassomeoftheotherissuesrelatedtoadministrationof5HT3antagonists.Ondansetron

OndansetronislicensedforuseintheUKinchildrenandyoungpeople(aged2‐18years)forreducingpost‐operativevomitingandiscommonlyused.Theproductlicenceisforondansetron0.1mg.kg‐1uptoamaximumof4mg.Undesirableeffectsassociatedwiththeuseofondansetroninchildrenarerareandclinicallyunimportant.Arecentpapersuggeststheremaybeapossiblereductionofanalgesiceffectsofparacetamolby5HT3antagonists.

43Thiseffectmaybeimportantbuthasnotyetbeenconfirmedinchildrenanddoesnotappeartobereflectedbyclinicalexperiencereportedsofar.

WhatistheoptimaldoseofondansetronforreducingPOVinchildren?

Theefficacyofondansetronwasstudiedindoseranges0.05to0.3mg.kg‐1andadoserelatedresponsewasdemonstrated44‐46.TheoveralloddsratioforPOVwas0.3644.Thesummaryoddsratioper0.1mg.kg‐1increaseindosewas0.43.

Subgroupanalysisofthepaediatricdata(1688children)showedthatinthepreventionofearlyvomiting,dosesof0.10and0.15mg.kg‐1wereclinicallyeffectivewithNNTof4.68and2.82respectively46.Inthepreventionoflatevomiting,0.10and0.15mg.kg‐1gaveNNTof5.35and3.67respectively.

Alowerdoseof0.05mg.kg‐1hadanoddsratiowithconfidenceintervals0.49to11.39andwasconsiderednoteffective47.

1++

A OndansetronisaclinicallyeffectiveantiemeticinchildrenundergoingproceduresassociatedwithahighriskofPOV.Thereisadoserelatedresponsewiththeoptimaldosebeing0.15mg.kg‐1.

17

ChildrenatincreasedriskofPOVshouldbegivenondansetron0.15mg.kg‐1.OndansetroncanbeusedasasingleagenttopreventearlyandlatePOV.

Whatroutesofadministrationareeffectiveforondansetron?Inameta‐analysisofchildrenundergoingtonsillectomy,studiesusingbothoralandintravenousondansetronwereincluded.TherewasnoevidencethatIVwasmoreeffectivethantheoralpreparationinchildrenundergoingtonsillectomy43.OneRCTof140childrenfoundoralondansetron0.15mg.kg‐1reducedPOVsignificantlywhereasanoraldoseof0.075mg.kg‐1wasnomoreeffectivethanplacebo48.Anoraldispersiblepreparationofondansetron4mgwaswelltoleratedbychildrenandefficacious49.

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A TheoralrouteisaseffectiveastheintravenousroutefortheadministrationofondansetroninpreventingPOVinchildren.

Theoralroutemaybeconsideredanalternativerouteforondansetronadministrationinsituationswhereintravenousaccessisnotavailable.

WhenisthebesttimetoadministerondansetrontoreducePOV?

InaRCTof120children,administeringondansetron0.10mg.kg‐1atthebeginningorendofsurgerymadenodifferencetoratesofearly,lateortotalPOV48.

ArecentCochranereviewofalladultandpaediatricPOVstudiesalsofoundnoevidencethattheriskofPOVdifferedingroupsgivenondansetronbeforeinduction,atinduction,intra‐operativelyorpost‐operatively50.

1+,1++

A 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+

GuidelinesonthePreventionofPostoperativeVomitinginChildren

A OndansetronismoreclinicallyeffectivethandroperidolormetoclopramideinpreventingPOVinchildren.OndansetronisequallyeffectivetodexamethasoneforearlyPOValthoughthelattermaybemoreeffectiveinreducinglatePOV.

OndansetronshouldbeconsideredasafirstlinetreatmentinchildrenwithahighriskofPOV.Combinationtherapywithasecondagentmayimproveitsefficacy(asdetailedbelow).

TropisetronTropisetronisaneffectiveanti‐emeticforPOVinchildren.ItdoesnotyethaveaproductlicenseforuseinchildrenintheUK.

Twostudiesusingtropisetron0.1‐0.2mg.kg‐1inchildrendemonstrateanoveralloddsratioof0.15forPOVwithnocleardoserelatedresponse44.Onestudyof120childrenfoundnodifferenceinoutcomewithearlyorlateadministrationoftropisetron52.Anotherstudyexaminedtheadditionofdexamethasonetotropisetronandfoundthatoverallvomitingwasreducedfrom53%(tropisetron0.1mg.kg‐1)to26%(tropisetron0.1mg.kg‐1+dexamethasone0.5mg.kg‐1)53.However,thisreductionwasnotdetecteduntilafter4hourspost‐operatively.

1+

A Tropisetronisaneffectiveanti‐emeticinchildrenathighriskofPOVandthisefficacyisincreasedbytheadditionofdexamethasone.

AlthoughtropisteroniseffectiveinreducingPOVinchildren,itisnotlicensedforuseinchildren.OndansetronshouldbeusedforreducingPOVinchildren.

GranisetronThreestudiesoftheefficacyofgranisetroninchildrenundergoingtonsillectomydemonstrateanoddsratioforPOVof0.11usingadoserangeof10‐80mcg.kg‐1.Thereisnocleardoserelatedresponseasseenwithondansetron44.FurthermoreCochranemeta‐analysissuggeststhattheeffectofgranisetrononreducingPOVmaybeoverestimatedbythesepapers.

1+

A Granisetronmaybeaneffectiveanti‐emeticforPOVinchildren.

MoreevidenceisrequiredontheefficacyofgranisetroninreducingPOVinchildren.

DolasetronInadosefindingstudyin204childrenundergoingdaycasesurgery,dolasetron350mcg.kg‐1wasaseffectiveatpreventingPOVasondansetron100mcg.kg‐1.54Onestudyon150dexamethasone‐pretreatedchildrenundergoingtonsillectomyshowed

1+

19 anoddsratioof0.25forPOVinchildrengivendolasetron55.

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

A Dolasetroniscontraindicatedforuseinchildrenandadolescentsunder18yearsold.

DolasetroniscontraindicatedforpreventionofPOVinchildren.

DexamethasoneDexamethasonehasincreasinglybecomerecognisedasaneffectiveanti‐emeticinchildrenonitsownandincombinationwith5HT3antagonists.

WhatistheoptimaldoseofdexamethasoneforreducingPOVinchildren?

Todate,therehasbeenonesystematicreviewondexamethasoneforpreventionofPOVonmixedadultandpaediatricstudies56.Analysisofthe7paediatricstudieswasnotreportedseparately.Dexamethasone1.0‐1.5mg.kg‐1versusplacebo(3trials)hadaNNTof10inpreventingearlyPOV(<6hr)andaNNTof3.2inpreventinglatePOV.

ACochranedatabasereviewin2003examiningchildrenundergoingtonsillectomyconcludedthatchildrengivenasingledoseofIVdexamethasone0.15to1.0mg.kg‐1

(max8‐25mg)werehalfaslikelytovomitinthefirst24hoursaftertonsillectomy(RelativeRisk=0.54,95%CI0.41‐0.74)57.RoutineuseofdexamethasoneinchildrenwasassociatedwithaNNTof4.

Adosefindingstudyofdexamethasone(0.25to1.0mg.kg‐1)in168childrenundergoingstrabismussurgerycomparedtoplaceboidentifiednoadditionalbenefitofusingdosesgreaterthan0.25mg.kg‐1.Forallgroupsstudied,therewasanNNTof2.2‐2.7.Inallgroupsreceivingdexamethasonetherewasnoevidenceofsideeffectsrelatingtoincreasedbloodsugarsorincreasedwoundinfectionrates58.

IVdexamethasonemaycauseperinealwarmthandshouldbeinjectedslowlyintheconsciouschild.Dexamethasonemayalsocauseinsomnolenceifgivenlateintheevening.Thereisnolong‐termfollow‐upstudyevaluatingeffectsofdexamethasoneontheimmunesysteminchildren.

ThreestudieshaveshownlowerdosesofdexamethasoneprovidesimilarclinicallysignificantpreventionofPOV59‐61:

Onestudyin140childrenuseddexamethasone150mcg.kg‐1(max8mg)andfoundanoverallreductioninPOVfrom71%to40%59.

1+,1++

GuidelinesonthePreventionofPostoperativeVomitinginChildren

Anotherstudycomparedlowdosedexamethasone(50mcg.kg‐1to250mcg.kg‐1)andfoundasignificantreductioninPOVevenwithdosesassmallas50mcg.kg‐160.TheNNTrangeforallgroupswas2‐2.9.

Inanotherstudy.125childrenundergoingadenotonsillectomyortonsillectomywereenrolledinadose‐escalatingstudyofdexamethasone:0.0625,0.125,0.25,0.5,or1mg.kg‐1,maximumdose24mg61.Therewasnodose‐escalationresponsetodexamethasoneforpreventingvomiting,reducingpain,shorteningtimetofirstliquidintake,ortheincidenceofvoicechange.Thelowestdoseofdexamethasone(0.0625mg.kg‐1)wasaseffectiveasthehighestdose(1.0mg.kg‐1)forpreventingPOVorreducingtheincidenceofothersecondaryoutcomes.Theauthorsconcludethereisnojustificationfortheuseofhigh‐dosedexamethasoneforthepreventionofPONVinthiscohortofchildren.SeveralreportsofacutetumourlysissyndromehavebeendescribedafterdexamethasonehasbeengiventoasusceptiblepatientindosesusedinpreventingPOV.62‐64TumourLysisSyndromeisapotentiallylethalconditionthatoccursparticularlyinhaematologicalmalignanciesaftertreatmentwithcytotoxictherapies.Dexamethasonehasinducedacutetumourlysisinpatientswithnon‐Hodgkinslymphoma62andacuteleukaemia.63‐64

A DexamethasonegivenalonereducestheriskofPOVinchildren.ItappearstobeparticularlyeffectiveinpreventinglatePOV(>6hr).

Adoseofdexamethasone150mcg.kg‐1providesgoodreductioninPOVwithnoadverseeffects.Dosesaslowasdexamethasone62.5mcg.kg‐1areefficaciousinreducingPOVinchildren.Dexamethasoneshouldnotbeusedinpatientsatriskoftumourlysissyndrome.

Metoclopramide

Metoclopramideindosesrangingfrom0.15mcg.kg‐1to0.25mcg.kg‐1hasbeenshowntoreducePOVinchildreninsomestudiesonly65‐67.Overall,thereislittlesupportintheliteraturefortheuseofmetoclopramideasananti‐emeticinchildrenfortheprophylaxisofpost‐operativevomitinginthedosestested(usually0.25mcg.kg‐1)15,45,68‐72.

Theextrapyramidaleffectsassociatedwithmetoclopramidearemorecommoninchildrenandhaveoccurredindosesusedtotreatpost‐operativevomiting.73

1+,1++

A Metoclopramideindosesof0.25mcg.kg‐1orlessdoesnotreliablyreducePOVinchildren.Furtherdose‐responsestudiesofmetoclopramidearerequiredtoseeifimprovedefficacyforpreventingPOVinchildrencanbeachievedathigherdoses.

Metoclopramideisnotareliableanti‐emeticinchildrenandisnotrecommendedforreducingPOVinchildren.Theroleofmetoclopramideinthetreatmentofestablishedpost‐operativevomitingrequiresfurtherinvestigation.

21

Prochlorperazine

Theanti‐emeticeffectofprochlorperazineinchildrenhasnotbeendetermined.Side‐effectshavebeenreportedwhenchildrenhavebeengivenprochlorperazine74.Thesearepredominantlyneurological,independentofdoseanddisappearedspontaneouslyafterdiscontinuationofthedrug.Impairedconsciousness,dyskinesia,pyramidalsignsandhypertonuswerethemainneurologicalmanifestations.

4

D ThereisnoevidenceintheliteraturefortheefficacyofprochlorperazineforreducingPOVinchildren.

ProchlorperazineisnotrecommendedforpreventionofPOVinchildren.

Cyclizine

Cyclizineisapiperazineantihistamineavailableover‐the‐counterandbyprescriptionintheUK,Canada,USandAustralia.InCanadatheuseofcyclizineforpatientsunder6yearsoldisoff‐label.Ithasbeenreportedasadrugwithpotentialforabuse75.Thereareonly2studiesontheuseofcyclizinefortreatingPOVinchildrenandneitherhadpositivefindings76‐77.Ithasbeenconcludedthatthereisnodetectableanti‐emeticeffectwithcyclizineandfurthermoretherewassignificantpainoninjection73.

1+

AThereiscurrentlynoevidencetosupporttheuseofcyclizineforPOVinchildreneitherforprophylaxisorfortreatment.

CyclizineisnotrecommendedforreducingPOVinchildren.

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

Twosystematicreviewsreportondimenhydrinate44,78.Inasystematicreviewandmeta‐analysisofanti‐emeticprophylaxisforchildrenundergoingtonsillectomy,dimenhydrinatewasnoteffectiveinthedosesstudied44.Inanothersystematicreview,theeffectivenessofdimenhydrinateforprophylaxisofpostoperativenauseaandvomitingwasreportedinbothadultsandchildren78.ThepaediatricstudieswereanalysedasasubgroupandtheNNTforchildrenwasreportedas4.76

1+,1++

GuidelinesonthePreventionofPostoperativeVomitinginChildrenforIV/IMadministrationand3.57forrectaladministrationofasingleequivalentdoseofdimenhydrinatehowevertheconfidenceintervalsarewide(2.56‐33.3and1.92‐20).

InasmallRCTof100childrenundergoingreconstructivesurgeryforburns,dimenhydrinate0.5mg.kg‐1wasfoundtobeasclinicallyeffectiveasondansetronbutmuchmorecosteffective79.Dimenhydrinate0.5mg.kg‐1hasalsobeenshowntobeeffectiveinstrabismussurgery80.Therearefewseriousside‐effectsandthecostbenefitratioisveryadvantageous.

A Insummary,thereisevidencetosupporttheuseofdimenhydrinateasprophylaxisinchildrenatmoderateorhighriskofpostoperativenauseaandvomitingexceptfortonsillectomy.

Dimenhydrinate0.5mg.kg‐1maybeusedtoreducePOVinchildrenexceptforchildrenundergoingtonsillectomy.

Therearenostudiesexaminingtheuseofdimenhydrinatetotreatpostoperativevomitingbutnonethelessitiscitedasrescuetherapyinonereviewarticleonperi‐operativenauseaandvomitinginchildren81.

4

DDimenhydrinatehasbeenusedforrescuetherapyinestablishedPOVinchildren.

DimenhydrinatemaybeusefulforrescuetherapyinestablishedPOVinchildren.

CombinationTherapy

OndansetronandDexamethasone

ThreerandomizedcontrolstudieshaveexaminedtheefficacyofondansetroncombinedwithdexamethasoneforpreventionofPOV82‐84.

Twolargestudiesdemonstratedthatondansetron50mcg.kg‐1combinedwithdexamethasone150mcg.kg‐1wasmoreeffectiveatpreventingPOVinchildrenundergoingstrabismussurgerythanondansetron150mcg.kg‐1aloneordexamethasone150mcg.kg‐1alone82,83.Astudyof193childrenundergoingstrabismussurgerycompareddexamethasone(150mcg.kg‐1)alonetodexamethasone(150mcg.kg‐1)plusondansetron(50mcg.kg‐1)82.Theadditionofondansetronreducedoverallvomitingfrom23%to5%.Astudyof200childrenundergoingstrabismussurgerycomparedondansetron(150mcg.kg‐1,maximumdose8mg)alonetodexamethasone(150mcg.kg‐1)plusondansetron(50mcg.kg‐1)83.TheincidenceofPOVwassignificantlylessinthecombinationgroup(9%)thanintheondansetrononlygroup(28%).

Inanotherstudynodifferencebetweentreatmentswasdetectedbetweenseveralcombinationtreatmentgroupscontainingondansetronandarangeofdexamethasonedosesandplacebo84.Thiswasattributedtotheparticularlylowbaselineincidenceofvomitingintheplacebogroup.

1+

23

A OndansetroncombinedwithdexamethasoneincreasestheeffectivenessinpreventingPOVinchildren.

InchildrenathighriskofPOV,combinationtherapyofondansetronanddexamethasoneshouldbegiven.IVOndansetron50mcg.kg‐1andIVdexamethasone150mcg.kg‐1shouldbegiventochildrenscheduledforadenotonsillectomyorstrabismussurgery.

Ondansetronandothercombinationanti‐emetictherapy

Ameta‐analysisexamininganti‐emeticcombinationtherapyincluded8paediatricstudies85.Althoughnoseparatedataoranalysiswaspresented,ondansetroncombinedwithdroperidolordexamethasonewasmoreeffectiveinpreventingPOVthanondansetronalone.

1+

A OndansetronwhencombinedwithdroperidolordexamethasoneismoreeffectiveinpreventingPOVthanondansetronalone.

Combinationanti‐emetictherapyshouldbeusedforchildrenathighriskofPOVorwheresingleagenttherapyhasfailedpreviously.Ondansetronanddexamethasoneisthemosteffectivecombinationofanti‐emeticsforreducingPOVinchildrenandisrecommendedforsituationsathighriskofPOV.

TropisetronandDexamethasone

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

1+,1++

A Tropisetronplusdexamethasoneismoreeffectivethantropisetronaloneforthepreventionofpostoperativenauseaandvomitinginchildrenundergoingtonsillectomy.

AlthoughIVtropisetronandIVdexamethasoneiseffectiveinreducingPOVinchildren,tropisetronisnotlicensedforuseinchildren.OndansetronanddexamethasoneshouldbeusedforreducingPOVinchildrenathighriskofPOV.

GuidelinesonthePreventionofPostoperativeVomitinginChildren

B.Anti‐emeticsforTreatingEstablishedPost‐operativeVomitinginChildren

Therearefewertrialsofefficacyofanti‐emeticsincontrollingestablishedPOVintherecoveryroominadultsandevenfewerinchildren87,comparedtothemultitudeoftrialsonprophylaxisofPOV.

Thereisonlyonetrialofasingledoseofondansetron(0.1mg.kg‐1)versusplaceboformanagingestablishedPOVinchildrenwhohavenotreceivedprophylactictherapy88: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.

Animportantstudyof428patientswhodevelopedPOVdespiteprophylaxiswithondansetron4mgIVdemonstratedthatgivingaseconddoseofondansetronwasaseffectiveasgivingplacebo89.Thisstudysuggeststhatifprophylaxiswithonedrugfails,aseconddrugfromanotherclassshouldbeusedforrescue.

1+

1+

B IVOndansetronmaybeeffectivefortreatingestablishedPOVinchildrenwhohavenotalreadyreceivedondansetron.

OndansetronisunlikelytobeeffectiveforestablishedPOVoccurringafterondansetronhasbeenadministered.

IVOndansetron0.15mg.kg‐1shouldbeusedtotreatestablishedPOVinchildrenwhohavenotalreadyreceivedondansetron.

Forchildrenwhohavealreadybeengivenondansetronprophylactically,itisrecommendedthatasecondantiemeticfromanotherclassshouldbegiven,suchasIVdexamethasone0.15mg.kg‐1injectedslowly.

25

3.Non‐PharmacologicalTreatmentofPost‐operativeVomitinginChildren

Avarietyofdifferentnon‐pharmacologicaloptionshavebeendescribedinordertopreventortreatPONVinchildrenbutthenumberofpublicationsaswellaspatientnumbersandstudydesignareofteninsufficienttoallowforameta‐analysisorstructuredreview(i.e.typeofbandagingfollowingbat‐earsurgery90).Thus,thissectionwillonlyfocusonthedifferenttypesofstimulationoftheP6acupuncturepoint(acupuncture,acupressure,orelectrical/laserstimulation)thathasbeenreportedinchildren.

StimulationoftheP6AcupuncturePointAmeta‐analysisin1999concludedvarioustypesofacustimulationinadultswereequallyeffectivecomparedtoanti‐emeticdrugsinpreventingvomitingaftersurgeryandthatsuchnon‐pharmacologicalternativesweremoreeffectivethanplaceboinpreventingPONVintheearlypostoperativeperiod91.Nobenefitwasfoundwithinthepaediatricpopulationinthisreview.

Sincethentwofurtherreviewshavebeenpublishedthatincorporatemorerecentpublicationswithinthisfield.InalargeCochranereportfrom2004(up‐dateofthe1999meta‐analysisabove,26trials,n=3,347)92acustimulationwasagainfoundtobeofbenefitinadultscomparedtocontrol.InthisCochranereport,acustimulationwasalsofoundtobeofbenefitinchildreninreducingtheincidenceofnauseaandalsopointingtoaborderlinesignificantreductioninvomitingcomparedtoshamtreatment.Whencomparedtoanti‐emeticdrugsusedforpreventionofPOV,acustimulationappearedtobeequallyeffective.

Recentlyameta‐analysisfocusingonchildrenincludedtwelveRCTs,mainlyperformedinthecontextofhigh‐risksurgery(e.g.adenotonsillectomyorstrabismussurgery)93.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++

A CurrentevidencebasesupportsacustimulationreducingPOVcomparedtothenon‐activecontrolsituation.AcustimulationappearstobeequallyeffectiveinpreventingPOVasanti‐emeticdrugsinchildren.

Theuseofacustimulationcanbeconsideredasanalternativetreatmenttoanti‐emeticmedicationsforsurgerywherethereisahigh‐riskPOVinchildren.

GuidelinesonthePreventionofPostoperativeVomitinginChildren

4.SummaryofFindings&Recommendations

PatientFactorsassociatedwithahighriskofPOV:

SurgicalproceduresassociatedwithahighriskofPOV:

27 AnaestheticfactorsaffectingtheincidenceofPOVinchildren:

SummaryofrecommendationsforpreventionofPOVinChildren:

GuidelinesonthePreventionofPostoperativeVomitinginChildren

SummaryofrecommendationsfortreatmentofestablishedPOVinChildren:

29

References1. ScottishIntercollegiateGuidelinesNetworkwww.sign.ac.uk

2. LermanJ.Surgicalandpatientfactorsinvolvedinpostoperativenausea&vomiting.BrJAnaesth1992;69(suppl1):24S‐32S

3. RoseJB,WatchaMF.Postoperativenausea&vomitinginpaediatricpatients.BrJAnaesth1999;83(1):104‐117

4. OlutoyeO,WatchaMF.Managementofpostoperativevomitinginpaediatricpatients.IntAnaesthesiolClinics2003;41(4):99‐117

5. D’ErricoC,Voepel‐LewisTD,SiewertMetal.Prolongedrecoverystayandunplannedadmissionofthepaediatricsurgicaloutpatient:anobservationalstudy.JClinAnesth1998;10:482‐487

6. PatelRI,HannallahRS.Anestheticcomplicationsfollowingpediatricambulatorysurgery.Anesthesiology1988;69:1009‐1012

7. GanTJ,SloanF,DearG,etal.Howmucharepatientswillingtopaytoavoidpostoperativenauseaandvomiting?AnesthAnalg2001;92:393–400.

8. ScuderiPE,JamesRL,HarrisL.etal.Anti‐emeticprophylaxisdoesnotimproveoutcomesafteroutpatientsurgerywhencomparedtosymptomaticrelief.Anesthesiology1999;90(2):360‐371

9. CohenMM,CameronCB,DuncanPG.Pediatricanaesthesiamorbidity&mortalityintheperioperativeperiod.AnesthAnalg1990;70:160‐167

10. EberhartLH,Geldnerg,KrankeP,etal.Thedevelopment&validationofariskscoretopredicttheprobabilityofpostoperativevomitinginpediatricpatients.AnesthAnalg2004;99:1630‐1637.

11. ByersGF,DoyleE,BestCYetal.Postoperativenauseaandvomitinginpaediatricsurgicalinpatients.PaediatrAnaesth1995;5:253‐256

12. GanTJ.Riskfactorsforpostoperativenausea&vomiting.AnesthAnalg2006;102:1884‐1898

13. KoivurantaM,LaaraE,SnareLetal.Asurveyofpostoperative&vomiting.Anaesthesia1997;52:443‐449

14. ApfelCC,LaaraE,KoivurantaMetal.Asimplifiedriskscoreforpredictingpostoperativenausea&vomiting:conclusionsfromcross‐validationsbetweentwocenters.Anesthesiology1999;91(3):693‐700.

15. ThomasM,WoodheadG,MasoodN,HowardR.Motionsicknessasapredictorofpostoperativevomitinginchildrenaged1‐16years.PaediatricAnesthesia2007;17:61‐3.

16. RowleyMP,BrownTC.Postoperativevomitinginchildren.AnaesthIntensiveCare1982;10(4):309‐313

17. GanTJ,MeyerT,ApfelCCetal.Consensusguidelinesformanagingpostoperativenausea&vomiting.AnesthAnalg2003;97:62‐71.

GuidelinesonthePreventionofPostoperativeVomitinginChildren18. EberhartLH,MorinAM,GeorgieffM.Themenstruationcycleinthepostoperative

phase.Itseffectontheincidenceofnausea&vomiting.Anaesthetist2000;49(6):532‐535

19. VandenBoschJE,MoonsKG,BonselGJetal.Doesmeasurementofpreoperativeanxietyhaveaddedvalueforpredictingpostoperativenausea&vomiting?AnesthAnalg2005;100:1523‐1532

20. WangSM,KainZN.Preoperativeanxietyandpostoperativenausea&vomitinginchildren:Isthereanassociation?AnesthAnalg2000;90:571‐575

21. KrankeP,ApfelCC,PapenfussTetal.Anincreasedbodymassisnoriskfactorforpostoperativenausea&vomiting.Asystematicreview&resultsoforiginaldata.ActaAnaesthesiolScand2001;45(2):160‐166

22. ChimbiraW,SweeneyBP.Theeffectofsmokingonpostoperativenausea&vomiting.Anaesthesia2000;55(6):1032‐1033

23. SinclairDR,ChungF,MezeGetal.Canpostoperativenausea&vomitingbeprevented?Anesthesiology1999;91(1):109‐118

24. TramèrM,MooreA,McQuayH.Preventionofvomitingafterpaediatricstrabismussurgery:asystematicreviewusingthenumbersneededtotreatmethod.BritJAnaesth1995;75(5):556‐561

25. JensenAB,ChristiansenDB,CoulthardKetal.Tropisetronreducesvomitinginchildrenundergoingtonsillectomy.PediatrAnaesth2000;10(1):69‐75

26. HamidSK,SelbyIR,SikichNetal.Vomitingafteradenotonsillarsurgeryinchildren:acomparisonofondansetron,dimehydrinate&placebo.AnesthAnalg1998;86:496‐500

27. AndersonBJ,RalphCJ,StewartAWetal.Thedose‐effectrelationshipformorphine&vomitingafterday‐casetonsillectomyinchildren.AnaesthIntensiveCare2000;28(2):155‐60

28. PaxtonD,TaylorRH,GallagherTM,etal.Postoperativeemesisfollowingotoplastyinchildren.Anaesthesia1995;50(12):1083‐1085

29. RidingsP,GaultD,KhanL.Reductioninpostoperativevomitingaftersurgicalcorrectionofprominentears.BritJAnaesth1994;72(5):592‐3

30. TramèrM,MooreA,McQuayH.OmittingN20ingeneralanaesthesia:meta‐analysisofintraoperativeawareness&postoperativeemesisinrandomisedcontrolledtrials.BritJAnaesth1996;76:186‐193

31. SplinterWM,KomocarL.N20doesnotincreasevomitingafterdentalrestorationsinchildren.AnesthAnalg1997;84(3):506‐508

32. SplinterWM,RobertsDJ,RhineEJetal.N20doesnotincreasevomitinginchildrenaftermyringotomy.CanJAnaesth1995;42:274‐6

33. PanditUA,MalviyaS,LewisIH.Vomitingafteroutpatienttonsillectomy&adenoidectomyinchildren:theroleofN20.AnesthAnalg1995;80:230‐233

34. ApfelCC,KrankeP,KatzMHetal.Volatileanaestheticsmaybethemaincauseofearlybutnotdelayedpostoperativevomiting;arandomisedcontrolledtrialoffactorialdesign.BritJAnaesth2002;85(5):659‐668

31 35. SneydJR,CarrA,ByromWDetal.Ameta‐analysisofnauseaandvomitingfollowing

maintenanceofanaesthesiawithpropofolorinhalationalagents.EurJAnaesthesiol1998;15:433‐445

36. MukherjeeK,EsuvaranathanV,StreetsC,JohnsonA,CarrAS.Adenotonsillectomyinchildren:acomparisonofmorphine&fentanylforperioperativeanalgesia.Anaesthesia2001;56(12):1193‐1197.

37. WennstromB,ReinsfeltB.Rectallyadministereddicloflenacreducesvomitingcomparedwithmorphineafterstrabismussurgeryinchildren.ActaAnaesthesiolScand2002;46(4):430‐434

38. PurdayJP,ReichertCC,MerrickPM.Comparitiveeffectsofthreedosesofintravenousketorolacormorphineonemesisandanalgesiaforrestorativedentalsurgeryinchildren.CanJAnaesth1996;43(3):221‐225

39. TramèrMR,Fuchs‐BuderT.Omittingantagonismofneuromuscularblockade:effectonPONV&riskofresidualparalysis.Asystematicreview.BritJAnaesth1999;82(3):379‐386

40. GoodarziM,MatarMM,ShafaM,TownsendJE,GonzalezI.AprospectiverandomizedblindedstudyoftheeffectofintravenousfluidtherapyonpostoperativenauseaandvomitinginchildrenundergoingstrabismussurgeryPediatricAnesthesia2006;16(1):49–53

41. SchreinerMS,NicolsonSC,MartinT,WhitneyL.Shouldchildrendrinkbeforedischargefromdaysurgery?Anesthesiology1992;76(4):528‐33.

42. KearneyR,MackC,EntwistleL.Withholdingoralfluidsfromchildrenundergoingdaysurgeryreducesvomiting.PediatricAnesthesia1998;8(4):331–336

43. PelissierT,AllouiA,PaeileC,EschalierA.Evidenceofacentralantinociceptiveeffectofparacetamolinvolvingspinal5HT3receptors.Neuroreport1995;6(11):1546‐1548.

44. BoltonCM,MylesPS,NolanT,SterneJA.Prophylaxisofpostoperativevomitinginchildrenundergoingtonsillectomy:asystematicreviewandmeta‐analysis.BrJAnaesth2006;97:593‐604

45. DominoKB,AndersonEA,PolissarNL,PosnerKL.Comparativeefficacyandsafetyofondansetron,droperidol,andmetoclopramideforpreventingpostoperativenauseaandvomiting:ameta‐analysis.[seecomment].Anesthesia&Analgesia1999;88(6):1370‐9.

46. FigueredoEDandCanosaLG.Ondansetronintheprophylaxisofpostoperativevomiting:ameta‐analysis.JClinAnesth.1998;10(3):211‐21.

47. RoseJB,BrennBR,CorddryDH,ThomasPC.Preoperativeoralondansetronforpediatrictonsillectomy.Anesthesia&Analgesia1996;82(3):558‐62.

48. CohenIT,JoffeD,HummerK,SoluriA.Ondansetronoraldisintegratingtablets:acceptabilityandefficacyinchildrenundergoingadenotonsillectomy.Anesthesia&Analgesia2005;101(1):59‐63.

GuidelinesonthePreventionofPostoperativeVomitinginChildren49. MadanR,PerumalT,SubramaniamK,ShendeD,SadashivamS,GargS.Effectof

timingofondansetronadministrationonincidenceofpostoperativevomitinginpaediatricstrabismussurgery.Anaesthesia&IntensiveCare2000;28(1):27‐30.

50. CarlisleJB,StevensonCA.Drugsforpreventingpostoperativenauseaandvomiting.CochraneDatabaseSystRev.2006Jul19;3:CD004125

51. SubramaniamB,MadanR,SadhasivamS,SennarajB,TamilselvanP,RajeshwariS,etal.Dexamethasoneisacost‐effectivealternativetoondansertroninpreventingPONVafterpaediatricstrabismusrepair.BritishJournalofAnaesthesia2001;86(1):84‐89.

52. GrossD.Earlyvslateintraoperativeadministrationoftropisetronforthepreventionofnauseaandvomitinginchildrenundergoingtonsillectomyand/oradenoidectomy.PediatricAnesthesia2006;16:444–450

53. HoltR,RaskP,CoulthardKP,SinclairM,RobertsG,VanDerWaltJ,etal.Tropisetronplusdexamethasoneismoreeffectivethantropisetronaloneforthepreventionofpostoperativenauseaandvomitinginchildrenundergoingtonsillectomy.PaediatricAnaesthesia2000;10(2):181‐8.

54. OlutoyeO,JantzenEC,AlexisR,RajchertD,SchreinerMS,WatchaMF.Acomparisonofthecostsandefficacyofondansetronanddolasetronintheprophylaxisofpostoperativevomitinginpediatricpatientsundergoingambulatorysurgery.Anesthesia&Analgesia2003;97(2):390‐6.

55. SukhaniR,PappasAL,LurieJ,HotalingAJ,ParkA,FluderE.Ondansetronanddolasetronprovideequivalentpostoperativevomitingcontrolafterambulatorytonsillectomyindexamethasone‐pretreatedchildren.Anesthesia&Analgesia2002;95(5):1230‐5.

56. HenziI,WalderB,TramerMR.Dexamethasoneforthepreventionofpostoperativenauseaandvomiting:Aquantitativesystematicreview.Anesthesia&Analgesia2000;90(1):186‐194.

57. StewardDL,WelgeJA,MyerCM.Steroidsforimprovingrecoveryfollowingtonsillectomyinchildren.CochraneDatabaseofSystematicReviews2003;(1):CD003997.

58. MadanR,BhatiaA,ChakithandyS,SubramaniamR,RammohanG,DeshpandeS,etal.Prophylacticdexamethasoneforpostoperativenauseaandvomitinginpediatricstrabismussurgery:adoserangingandsafetyevaluationstudy.Anesthesia&Analgesia2005;100(6):1622‐6.

59. SplinterWM,RobertsDJ.Dexamethasonedecreasesvomitingbychildrenaftertonsillectomy.Anesthesia&Analgesia1996;83(5):913‐6.

60. MathewPJ,MadanR,SubramaniamR,BhatiaA,MalaCG,SoodanA,etal.Efficacyoflow‐dosedexamethasoneforpreventingpostoperativenauseaandvomitingfollowingstrabismusrepairinchildren.Anaesthesia&IntensiveCare2004;32(3):372‐6.

61. KimMS,CotéCJ,CristoloveanuC,RothAG,VornovP,JenningsMA,MaddalozzoJP,SullivanC.Thereisnodose‐escalationresponsetodexamethasone(0.0625‐1.0mg/kg)inpediatrictonsillectomyoradenotonsillectomypatientsforpreventing

33

vomiting,reducingpain,shorteningtimetofirstliquidintake,ortheincidenceofvoicechange.AnesthAnalg.2007;104(5):1052‐8

62. DhingraK,Newcom,SR.Acutetumorlysissyndromeinnon‐Hodgkinlymphomainducedbydexamethasone.Am‐J‐Hematol.1988Oct;29(2):115‐6

63. OsthausWA,LinderkampC,BünteC,JüttnerB,SümpelmannR.Tumorlysisassociatedwithdexamethasoneuseinachildwithleukemia.PaediatricAnaesthesia2008;18(3):268‐70.

64. McDonnellC,BarlowR,CampisiP,GrantR,MalkinD.Fatalperi‐operativeacutetumourlysissyndromeprecipitatedbydexamethasone.Anaesthesia2008;63(6):652‐5.

65. LinDM,FurstSR,RodarteA.Adouble‐blindedcomparisonofmetoclopramideanddroperidolforpreventionofemesisfollowingstrabismussurgery.Anesthesiology1992;76(3):357‐61.

66. BroadmanLM,CeruzziWetal.Metoclopramidereducestheincidenceofvomitingfollowingstrabismussurgeryinchildren.Anesthesiology1990;72(2):245‐48.

67. FerrariLR,DonlonJV.Metoclopramidereducestheincidenceofvomitingaftertonsillectomyinchildren.AnesthAnalg1992;75(3):351‐4.

68. Shende,D.,Mandal,N.G.etalEfficacyofondansetronandmetoclopramideforpreventingpostoperativeemesisfollowingstrabismussurgeryinchildrenAnaesthesia1997;52(5):496‐500.

69. HenziI,WalderB,TramerMR.Metoclopramideinthepreventionofpostoperativenauseaandvomiting:aquantitativesystematicreviewofrandomized,placebo‐controlledstudies.BritishJournalofAnaesthesia1999;83(5):761‐71.

70. PendevilleE,VeyckemansF,BovenMJ,SteinerJR.Openplacebocontrolledcomparisonoftheentiemeticeffectofdroperidol,metoclopramideoracombinationofbothinpaediatricstrabismussurgery.ActaAnaesthesiologicaBelgica1993;44(1):3‐10.

71. KovacAL.Preventionandtreatmentofpostoperativenauseaandvomiting.Drugs2000;59(2):213‐243.

72. TramèrMR.Arationalapproachtothecontrolofpostoperativenauseaandvomiting:evidencefromsystematicreviews.Partl.Efficacyandharmofanti‐emeticinterventions,andmethodologicalissues.ActaAnaesthesiologicaScand2001;45:4‐13.

73. Casteels‐vanDaeleM,JaekenJetal.Dystonicreactionsinchildrencausedbymetoclopramide.ArchivesofDiseasesinChildhood1970;45:130‐3.

74. LankampDJ,WillemseJ,PikaarSA,vanHeystAN.Prochlorperazineinchildhood:side‐effects.ClinNeurolNeurosurg1977;80(4):264‐71.

75. ThePharmaceuticalJournalonline2005;274(7354):775http://www.pjonline.com/Editorial/20050618/society/ethics.html

76. O'BrienCM,TitleyG,WhitehurstP.Acomparisonofcyclizine,ondansetronandplaceboasprophylaxisagainstpostoperativenauseaandvomitinginchildren.Anaesthesia2003;58(7):707‐11.

GuidelinesonthePreventionofPostoperativeVomitinginChildren77. DrakeR,AndersonBJ,PerssonMA,ThompsonJM.2001.Impactofananti‐emetic

protocolonpostoperativenauseaandvomitinginchildren.PaediatricAnaesthesia2001;11(1):85‐91.

78. KrankeP,MorinAM,RoewerN,EberhartLH.Dimenhydrinateforprophylaxisofpostoperativenauseaandvomiting:ameta‐analysisofrandomizedcontrolledtrials.ActaAnaesthesiolScand2002;46(3):238‐44.

79. McCallJE,StubbsK,SaylorsS,PohlmanS,IversB,SmithS,FischerCG,KopchaR,WardenGJ.Thesearchforcost‐effectivepreventionofpostoperativenauseaandvomitinginthechildundergoingreconstructiveburnsurgery:ondansetronversusdimenhydrinate.BurnCareRehabil.1999;20(4):309‐15.

80. VenerDF,CarrAS,SikichN,BissonnetteB,LermanJ.Dimenhydrinatedecreasesvomitingafterstrabismussurgeryinchildren.AnesthAnalg.1996;82(4):728‐31.

81. OlutoyeO,WatchaMF.2003.Managementofpostoperativevomitinginpediatricpatients.IntAnesthesiolClin.41(4):99‐117.

82. SplinterWM.Preventionofvomitingafterstrabismussurgeryinchildren:Dexamethasonealoneversusdexamethasonepluslow‐doseondansetron.PaediatricAnaesthesia2001;11(5):591‐595.

83. SplinterWM,RhineEJ.Low‐doseondansetronwithdexamethasonemoreeffectivelydecreasesvomitingafterstrabismussurgeryinchildrenthandoeshigh‐doseondansetron.Anesthesiology1998;88(1):72‐5.

84. CelikerV,CelebiN,CanbayO,BasgulE,AyparU.Minimumeffectivedoseofdexamethasoneaftertonsillectomy.PaediatricAnaesthesia2004;14(8):666‐9.

85. Habib,AS,El‐MoalemHE,GanTJ.Theefficacyofthe5‐HT3receptorantagonistscombinedwithdroperidolforPONVprophylaxisissimilartotheircombinationwithdexamethasone.Ameta‐analysisofrandomizedcontrolledtrials.CanJAnaesth.2004Apr;51(4):311‐9.

86. HoltR,RaskP,CoulthardKP,SinclairM,RobertsG,VanDerWaltJ,etal.Tropisetronplusdexamethasoneismoreeffectivethantropisetronaloneforthepreventionofpostoperativenauseaandvomitinginchildrenundergoingtonsillectomy.PaediatricAnaesthesia2000;10(2):181‐8.

87. OlutoyeO,WatchaMF.Managementofpostoperativevomitinginpediatricpatients.InternationalAnesthesiologyClinics2003:41(4);99‐117.

88. KhalilS,RodarteA,WeldonBCetal.IVondansetroninestablishedpostoperativeemesisinchildren.Anesthesiology.1996;85:270‐76

89. KovacAL,O'ConnorTA,PatemanMH.EfficacyofrepeatIVdosingofondansetronincontrollingpostoperativenausea&vomiting:arandomized,double‐blind,placebo‐controlledmulticentertrial.JClinAnesth1999;11:453‐459

90. RidingsP,GaultD,KhanL.Reductioninpostoperativevomitingaftersurgicalcorrectionofprominentears.BrJAnaesth1994;72:592‐593.

91. LeeA,DoneML.Theuseofnon‐pharmacologictechniquestopreventpostoperativenauseaandvomiting:ameta‐analysis.AnesthAnalg1999;88:1362‐1369.

35 92. LeeA,DoneML.StimulationofthewristacupuncturepointP6forpreventing

postoperativenauseaandvomiting.CochraneDatabaseofSystematicReviews2004;3:CD003281.

93. DuneLS,ShiaoSY.Metaanalysisofacustimulationeffectsonpostoperativenauseaandvomitinginchildren.Explore(NY)2006;2:314‐320.