apa guidelines on the prevention of postoperative vomiting in children

8/2/2019 APA Guidelines on the Prevention of Postoperative Vomiting in Children

1/35

TheAssociationof

PaediatricAnaesthetistsof

GreatBritain&Ireland

ContributingAuthors:

AlisonSCarr

SimonCourtman

HelenHoltby

NeilMorton

ScottJacobson

LiamBrennan

DavidBaines

PerArneLnnqvist

JackiePope

Spring 2009

GuidelinesonthePreventionof

PostoperativeVomitinginChildren


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GuidelinesonthePreventionofPostoperativeVomitinginChildren

ContributingAuthors/MembersoftheGuidelinesGroup:

DrAlisonSCarr(Chair)

ConsultantPaediatricAnaesthetist

PlymouthHospitalsNHSTrust

DerrifordHospitalPlymouthPL68DH

HonorarySeniorLecturer

PeninsulaCollegeofMedicineandDentistry

Plymouth

[email protected]

DrLiamBrennan


AddenbrookesHospital

CambridgeUniversityHospitalsNHSFoundationTrust

HillsRd

CambridgeCB20QQ

DrSimonCourtman



DerrifordHospital

PlymouthPL68DH

DrDavidBaines

ClinicalAssociateProfessor

Head,DeptofAnaesthesia

TheChildren'sHospitalatWestmead

NSWAustralia

DrHelenHoltby

DirectorofCardiovascularAnaesthesia

HospitalforSickChildren

Toronto

Canada

ProfessorPerArneLnnqvist

SeniorConsultant

PaediatricAnaesthesia&IntensiveCare

AstridLindgrensChildrensHospital

KarolinskaUniversityHospital

Stockholm,Sweden

Professsor

DeptofPhysiologyandPharmacology

KarolinskaInstitute

17177Stockholm


3/35

3DrNeilMorton


YorkhillChildrensHospital

Glasgow

SeniorLecturer

UniversityofGlasgow

MsJackiePope

Pharmacist


DerrifordHospital

PlymouthPL68DH

DrScottJacobson

Resident

FamilyMedicine,

UniversityofNevada,

UnitedStatesofAmerica

FormerlyClinicalFellow

TheHospitalforSickChildren

Toronto

Canada


4/35


Wewouldliketothankthefollowingpeoplewhoprovidedfeedbackonthedraft

guidelinescirculatedtoAPAmembersandlinkmeninFebruary2008:

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


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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,typeofsurgery

11

C.AnaestheticFactors

Nitrousoxide,volatileagents,perioperativeopioids,

anticholinesterases,perioperativefluids

13

2.PharmacologicaltreatmentofPOVinchildren

A.Antiemeticsforprevention&reductionofPOVinchildren

16

SingleAgents: 16

5HT3Antagonists,Dexamethasone,Metoclopramide,

Prochlorperazine,Cyclizine,Dimenhydrinate

CombinationTherapy: 22

Ondansetronanddexamethasone,Ondansetronandother

combinationantiemetictherapy,Tropisetron

B.AntiemeticsfortreatingestablishedPOVinchildren 24

3.NonpharmacologicaltreatmentofPOVinchildren 25

StimulationoftheP6Acupuncturepoint

4.Summaryoffindings&recommendations 26

References 29


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KeytoEvidenceStatementsandGradesofRecommendation:


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7IntroductionPostoperativeVomiting(POV)isanimportantcauseofmorbidityinchildren.Thisreportfor

theAssociationofPaediatricAnaesthetistsofGreatBritain&Irelandinvestigatesthe

causesofpostoperativevomitinginchildrenandsummarisestheefficacyoftreatments

usedtopreventandtreatpostoperativevomitinginchildren.TheguidelineshavebeenpreparedusingSIGNMethodology

1drawingtogetheravailableevidenceand

recommendingbestpracticebasedontheavailableevidenceandontheclinicalexperience

oftheguidelinesdevelopmentgroup.

RemitoftheGuidelineTheguidelineseekstoanswerthefollowingquestions:

DraftguidelinesweredistributedtoAPAmembersandLinkmeninFebruary2008for

feedbackandweremadeavailableonthewebsiteoftheAssociationofPaediatric

AnaesthetistsofGreatBritain&Irelandforcomment.

Theseguidelinesarenowinthefinalversion.Theyhavebeenwritteningoodfaithandwill

berevisedasnewinformationbecomesavailable.Shouldthereaderfindanyuseful

additionalcontentpleasecontacttheChairofthePOVGuidelinesgroupbyemailtoinform

afuturerevision.


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Glossary

NNT:Numberneededto

treat

Thenumberofpatientswhoneedtobetreatedtoreduce

theexpectednumberofcasesofadefinedendpointbyone.

Metaanalysis Astatisticalmethodthatcombinestheresultsof

independenttrialstogiveapreciseestimateoftreatmenteffect.

Casecontrolstudy Astudythatcomparespatientswithanidentifiedoutcome

againstpatientswithoutthatoutcome,andreviewingthem

toseeiftheyhadanexposureofinterest.

Cohortstudy Astudyinwhichsubjectswhohaveacertaincondition

and/orreceiveaparticulartreatmentarefollowedovertime

andarecomparedwithanothergroupwhoarenotaffected

bythatcondition.

Systematicreview Areviewofrelevantliteraturefocusedonaspecificquestion

thattriestoidentify,evaluateandsynthesizeallhighquality

researchevidencerelevanttothatquestion.

Randomisedcontrol

study

Astudywherebydifferenttreatmentsarerandomly

allocatedtostudyparticipants.Thisattemptstoensuresthat

bothknownandunknownconfoundingfactorsareevenly

distributedbetweentreatmentgroups,therebyreducing

errorandbias.

Sensitivity Probabilityofapositivetestamongpatientswithadisease

Specificity Probabilityofanegativetestamongpatientswithouta

disease

Positive(negative)

predictivevalue

Theratioofthetruepositives(negatives)dividedbythesum

ofthetruepositives(negatives)andfalsepositives

(negatives).

Oddsratio Theratiooftheoddsofaneventoccurringinonegroupto

theoddsofitoccurringinanothergroup.Anoddsratioof1

indicatesthattheconditionoreventunderstudyisequally

likelyinbothgroups.Itprovidesanestimate(withconfidence

interval)fortherelationshipbetweentwobinary("yesor

no")variables.

Confidenceinterval Anindicationofthereliabilityofanestimate.Theconfidence

levelwilldefinehowlikelytheintervalistocontainthe

parameter.

Relativerisk Theratiooftheprobabilityofaneventoccurringina

treatmentgroupversusthecontrolgroup.


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9

1.IdentifyingChildrenatHighRiskofPostoperative

Vomiting

Background

PostoperativeVomiting(POV)isapproximatelytwiceasfrequentamongstchildrenas

adultswithanincidenceof1342%inallpaediatricpatients2,3.SeverePOVcanresultina

rangeofcomplicationsincludingwounddehiscence,dehydrationandelectrolyteimbalance

andpulmonaryaspiration4.Itisoneoftheleadingcausesofparentaldissatisfactionafter

surgeryandistheleadingcauseofunanticipatedhospitaladmissionfollowingambulatory

surgerywithresultingincreasedhealthcarecosts5,6.Importantly,noresearchhasfocused

onthechildrensperspectiveofPOV,andwhethertheyperceivethissymptomwiththesamedistressandloathingasadults7.

IdentifyingchildrenathighriskofPOVisbeneficialasprophylacticantiemetictherapycan

thenbetargetedatthisgroup.Indiscriminateprophylaxisisprobablyunnecessaryasitis

financiallycostlyandmayresultinexcessiveadversedrugreactions8.Researchintothis

importantareaishamperedbythedifficultyindiagnosingnauseainyoungerchildren.

Hence,vomitingandretchingareusedastheendpointsinmostofthepaediatric

literatureonthissubject3.

ThemainriskfactorsforPOVinchildrenmaybeconsideredinthefollowingcategories:

Patientrelatedissues Surgicalfactors Anaesthetic(technique&drugsusedinperioperativeperiod)

A.PatientFactors

Age

PaediatricpatientshaveahigherincidenceofPOVcomparedtoadultswithchildren

over5yearsofagehavingarounda3450%overallriskofvomitingaftersurgery.

Thelowestincidenceoccursininfancy(5%incidenceofemesis)whilethepreschool

childhasa20%riskofvomiting9.Inacohortstudyof1401children


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HistoryofPOV

Thishasprovedtobeanimportantriskfactorinthemajorityofstudiesintheadult

andpaediatricPOVliteratureandisincludedinalloftheriskscoringsystemstoaid

predictionofPOVthathavebeenpublishedtodate12.Aspecificpaediatriccohort

studyidentifiedpreviousPOVandPOVinaparentorsiblingasimportant

independentriskfactors10

.Acombinedadultandpaediatricstudy(with


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11

Postpubertalgirlsshouldbeconsideredforprophylacticantiemeticmedication.

Preoperativeanxiety

AlthoughpreoperativeanxietyhasbeenshowntobeaweakriskfactorforPOVin

adults,thiswasnotconfirmedinaprevioussmall,butwellconductedstudyin

schoolagechildren19,20.

2

Obesity

Earlystudiesfromthe1950sand1960ssuggestedanassociationbetweenobesity

andPOVinadults.However,asystematicreviewwithadjustmentformultiple

confoundingfactorsfailedtoconfirmtheseearlierfindings21.Thereisno

comparableevidenceregardingarelationshipbetweenobesityandPOVin

children.

1+

adults

Smoking

AdultsmokersarelesssusceptibletoPOVfromconvincingdatainseveralstudies

14,22,23.Nodataonthistopicarepublishedinchildren.Arecentreviewposedthe

intriguingquestionifchildrenofsmokershaddecreasedPOVduetopassive

smoking4.

2+

adults

B.SurgicalFactors

Durationofsurgery

TheincidenceofPOVincreaseswithlongerdurationofsurgeryandanaesthesiain

bothadultandpaediatricstudies10,23.Surgeryundergeneralanaesthesiaof>30

minutesdurationwasidentifiedasanindependentriskfactorinalargepaediatric

studywithanoddsratioof3.2510.Halfofthepublishedriskscoringsystemsfor

POVinadultsandchildrenincludedurationofsurgeryasanimportantriskfactor17.

2++

C POVincreasessignificantlyifoperativeproceduresunderGAlastmorethan30minutes.

Typeofsurgery

ThestatusoftypeofsurgeryasariskfactorforPOViscontroversial.Althoughnumerous

studieshaveidentifiedavarietyofproceduresasbeingassociatedwithincreasedriskof

POV,thereisoftenconflictingevidencebetweenstudiesforthesameprocedure.Thisarea

ofPOVresearchsuffersfromtheproblemofseparatingtruefromsurrogateriskfactors3.

Forexample,certaintypesofsurgeryassociatedwithhighpostoperativeopioid

requirementsmightbethesurrogateforincreasedPOVriskratherthantheprocedure

itself.ThishasresultedinmostoftheestablishedriskscoresforPOVnotincludinganytype

ofsurgeryintheirriskmodel10.


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Withtheseconsiderationsinmind,thefollowingproceduresinchildrenhavebeen

associatedwithincreasedPOVrisk:

a.Strabismussurgery

Thisisperhapsthepaediatricsurgicalprocedurethathasthestrongestevidenceof

POVriskwithahighfrequencyofemeticepisodesreportedinasystematicreview

(meanincidencelatevomiting59%,butashighas87%inoneoftheincludedstudies)

24.Itistheonlysurgicalprocedureincludedintheestablishedpaediatric

POVriskscorewithanoddsratioof4.33,thehighestriskfactorofthefour

independentfactorsidentifiedinthisstudy10.

1++

A ChildrenundergoingstrabismussurgeryareathighriskofPOV.

MinimisingPOVfollowingstrabismussurgeryrequiresamultimodalapproach

utilisingantiemetics,dexamethasoneandavoidingearlymobilisationinthe

recoveryperiod.

b.AdenotonsillectomyWithoutantiemeticprophylaxis,ahighproportionofchildrenundergoing

adenotonsillectomywillexperienceatleastoneepisodeofpostoperativevomiting

(89%withoutprophylaxisinoneseries)11,25,26

.However,manyofthesestudies

sufferfromthedrawbackofthecompoundingeffectofperioperativeopioid

administrationthatmaybeactingasasurrogateriskfactor,asintheabsenceof

opioidsinonestudyonly11%ofchildrenvomited27.

1+

A ChildrenundergoingadenotonsillectomyareatincreasedriskofPOV.

MinimisingPOVisessentialforasuccessfuldaycasetonsillectomyprogramme.

Scrupuloussurgicaltechniquetodecreaseswallowedblood,avoidanceoflongactingopioidanalgesiaandprophylacticantiemeticsanddexamethasonearekey

factorsinachievingthisgoal.

c.Otoplasty

Otoplastyinchildrenisrecognisedforitsemeticpotentialwithanincidenceof

vomitingintheabsenceofantiemeticprophylaxisof60%28.However,surgical

dressings,inparticularpackingoftheexternalearcanal,mayinfluencethe

incidenceofPOVinthesepatients29.

2

d.Otherprocedures

Groinsurgery(herniotomyandorchidopexy)andpenilesurgeryhaveamodest

increasedincidenceofPOV,buttheevidenceisfromolderstudieswithnumerous

compoundingvariablessuchasopioidadministration11,16.

2

Theevidencethatproceduresotherthanstrabismussurgeryand

adenotonsillectomyareassociatedwithahighincidenceofPOVisless

compelling.However,whentheconsequencesofPOVmaysignificantlyaffect

clinicaloutcomese.g.resultinadmissionafterdaycasesurgery,consideration

shouldbegiventousingprophylacticantiemetics.


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13

C.Anaestheticfactors

AvarietyofanaestheticrelatedfactorshavebeenimplicatedinproducingincreasedPOV

inchildren.However,fewofthesefactorsareincludedinanyofthePOVriskscoring

systemsinthepublishedliteratureforpaediatricpatients4.

Nitrousoxide

Amixedadultandpaediatricsystematicreviewconcludedthatomissionofnitrous

oxidereducedtheincidenceofpostoperativevomitingbutnotnauseainhighrisk

patientswithaNNTof5.Thereductioninemesis,byavoidingnitrousoxide,was

achievedatthecostofanincreasedriskofintraoperativeawareness30.

Inchildren,avoidingnitrousoxidehasconflictingeffectsonPOV;itproducesasmall

reductioninearlyPOVfollowingdentalsurgerybutnotaftergrommetinsertion

withoutanydifferenceinlatePOVrateswitheitherprocedure31,32.InasmallRCT,

therewasnodifferenceinPOVratesinpaediatricT&Aspatientswhoreceived

nitrousoxidecomparedtothosewhodidnotreceivetheagent.33

1+,

2

C TheuseofnitrousoxidedoesnotappeartobeassociatedwithahighriskofPOVinchildren

Nitrousoxidemaybeusedforanaesthesiainchildrenwithoutincreasingthe

incidenceofPOV.

Volatileagents

Althoughmodernvolatileagentsarelessemetogenicthanolderagents(e.g.ether),

thereisevidencethatvolatileagentsmaysignificantlycontributetoearlyPOV

particularlyinhighriskpatients.Thereisalsoastrongdoseresponserelationship

betweenPOVanddurationofexposuretovolatileagents34.Volatileagentsarefar

moreemetogenicwhenusedformaintenanceofanaesthesiawhencomparedto

propofolmaintenanceinalargemetaanalysis35.Thereislittleevidencethatanyof

themodernagentsislessormoreemetogenicthantheothers34,35.

1++,

1+

A UseofvolatileanaestheticagentsisassociatedwithincreasedriskofemesisparticularlyinchildrenwhohaveotherriskfactorsforPOV.

Itisrecommendedthattotalintravenousanaesthesiashouldbeconsideredwhen

childrenwhoareathighriskofPOVundergosurgerythathasahighriskof

producingPOV.

Perioperativeopioids

Despitethewidelyheldbeliefthatperioperativeopioidadministrationisstrongly

implicatedinincreasedPOV,theevidencefromtheliteratureislesscategorical.

Intraoperativeopioiduseinchildrenintwolargestudieswasassociatedwith

reducedoronlyslightincreasedincidenceofPOV

10,34

,whereaspostoperativeadministrationinboththesestudieswasassociatedwithincreasedPOVriskwith

1+,

1


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oddsratiosof1.64and2.3respectively.

Conversely,theuseofperioperativemorphineinchildrenisassociatedwith

increasedPOVriskforarangeofproceduresincludingadenotonsillectomy,

strabismussurgeryanddentalsurgery27,36,37,38

Althoughadministrationofperioperativeopioidsisincludedinhalfofthepublished

adultPOVriskscores,opioidusewasnotregardedasanindependent,statisticallysignificantpredictorofPOVinthemostwidelyquotedpaediatricPOVriskscoring

system.11

B UseofopioidsmaybeassociatedwithincreasedriskofPOVparticularlyiflongeractingagentsareusedinthepostoperativeperiod

Theanaesthetistshouldtrytoachievesatisfactorypostoperativeanalgesia

withouttheuseofopioidswheneverpossibleifPOVistobeminimised,

particularlyinhighriskpatients.

Useofregionalandlocalanaesthesiatechniquesarerecommendedwhere

appropriatetoreducetheneedforopioids.

Useofanticholinesterasedrugs

Antagonismofneuromuscularblockadehasbeenassociatedwithincreasedriskof

POV.Inasystematicreviewofthissubjectinamixedadultandpaediatric

population(25%children),higherdoseneostigmine(>2.5mgsinadults)was

associatedwithasignificantlyincreasedriskofPOV,althoughthestudydidnot

analysethepaediatricandadultpatientsseparately39.

2

D UseofanticholinesterasedrugsmayincreasePOVinchildren.

InsituationswhereachildisathighriskofPOV,anaesthesiawithoutmuscle

relaxantsshouldbeconsideredtoavoidtheriskofrequiringreversalof

neuromuscularblockade.

PerioperativeFluids

Forminorsurgicalprocedures,givinglargevolumesofIVcrystalloidintraoperatively

reducedPOVinchildrenafterstrabismussurgeryinthefirst24hours

aftersurgery.40Onehundredchildrenwererandomlyassignedtoreceive

30mlkg

1

h

1

(superhydrationgroup)or10mlkg

1

h

1

(controlgroup)oflactatedRinger'ssolutionintraoperatively.Nauseaandvomitingoccurredin11(22%)of

patientsinthesuperhydrationgroupand27patients(54%)ofthecontrolgroup(P=

0.001).

Inastudyofchildrenadmittedfordaycasesurgery,989children(aged1month

18years)wererandomisedtotwogroups:mandatorydrinkersandelective

drinkers.41The464mandatorydrinkershadtodemonstrateabilitytodrinkclear

liquidswithoutvomitingpriortodischargewhereas525electivedrinkerschose

whethertheywishedtodrinkornotbeforedischarge.Allpatientsreceived

adequateIVfluidstosupplyacalculated8hfluiddeficitpriortodischarge.The

incidenceofvomitingdidnotdifferbetweengroupsintheoperatingroom,the

postanesthesiacareunitorafterdischargefromhospital.Inthedaysurgeryunit,

1+,

2+


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15only14%electivedrinkersvomitedcomparedto23%mandatorydrinkers(P


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2.PharmacologicalTreatmentofPostoperativeVomiting

inChildren

Inthissection,theevidencefortheefficacyofcommonlyusedantiemeticsinreducing

postoperativevomitinginchildrenisreportedandrecommendationmadeforpreventing

POVinchildren.InadditionrecommendationsaremadeontreatingestablishedPOVin

children.

A.AntiemeticsforPrevention&ReductionofPost

operativeVomitinginChildren

5HT3Antagonists

5HT3antagonistsareeffectiveantiemeticsinchildren.Therearealargenumberofstudies

availableexaminingtheincreasingnumberoftheseagentsavailableaswellassomeofthe

otherissuesrelatedtoadministrationof5HT3antagonists.

Ondansetron

OndansetronislicensedforuseintheUKinchildrenandyoungpeople(aged218years)

forreducingpostoperativevomitingandiscommonlyused.Theproductlicenceisfor

ondansetron0.1mg.kg1uptoamaximumof4mg.Undesirableeffectsassociatedwiththeuseofondansetroninchildrenarerareandclinicallyunimportant.Arecentpapersuggests

theremaybeapossiblereductionofanalgesiceffectsofparacetamolby5HT3antagonists.

43Thiseffectmaybeimportantbuthasnotyetbeenconfirmedinchildrenanddoesnot

appeartobereflectedbyclinicalexperiencereportedsofar.

WhatistheoptimaldoseofondansetronforreducingPOVinchildren?

Theefficacyofondansetronwasstudiedindoseranges0.05to0.3mg.kg1anda

doserelatedresponsewasdemonstrated4446.TheoveralloddsratioforPOVwas

0.3644.Thesummaryoddsratioper0.1mg.kg

1increaseindosewas0.43.

Subgroupanalysisofthepaediatricdata(1688children)showedthatinthe

preventionofearlyvomiting,dosesof0.10and0.15mg.kg1wereclinicallyeffective

withNNTof4.68and2.82respectively46.Inthepreventionoflatevomiting,0.10

and0.15mg.kg1gaveNNTof5.35and3.67respectively.

Alowerdoseof0.05mg.kg1hadanoddsratiowithconfidenceintervals0.49to

11.39andwasconsiderednoteffective47.

1++

A OndansetronisaclinicallyeffectiveantiemeticinchildrenundergoingproceduresassociatedwithahighriskofPOV.Thereisadoserelatedresponsewiththe

optimaldosebeing0.15mg.kg1.


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17

ChildrenatincreasedriskofPOVshouldbegivenondansetron0.15mg.kg1.

OndansetroncanbeusedasasingleagenttopreventearlyandlatePOV.

Whatroutesofadministrationareeffectiveforondansetron?

Inametaanalysisofchildrenundergoingtonsillectomy,studiesusingbothoraland

intravenousondansetronwereincluded.TherewasnoevidencethatIVwasmore

effectivethantheoralpreparationinchildrenundergoingtonsillectomy43.

OneRCTof140childrenfoundoralondansetron0.15mg.kg1reducedPOV

significantlywhereasanoraldoseof0.075mg.kg1wasnomoreeffectivethan

placebo48.Anoraldispersiblepreparationofondansetron4mgwaswelltolerated

bychildrenandefficacious49.

1+

ATheoralrouteisaseffectiveastheintravenousroutefortheadministrationof

ondansetroninpreventingPOVinchildren.

Theoralroutemaybeconsideredanalternativerouteforondansetron

administrationinsituationswhereintravenousaccessisnotavailable.

WhenisthebesttimetoadministerondansetrontoreducePOV?

InaRCTof120children,administeringondansetron0.10mg.kg1atthebeginning

orendofsurgerymadenodifferencetoratesofearly,lateortotalPOV48.

ArecentCochranereviewofalladultandpaediatricPOVstudiesalsofoundnoevidencethattheriskofPOVdifferedingroupsgivenondansetronbefore

induction,atinduction,intraoperativelyorpostoperatively50.

1+,

1++

A Thereisnoevidencedemonstratingabenefitoftimingondansetronadministrationinchildrenwithrespecttothetimeofsurgery.

Ondansetronmaybegivenbeforeinduction,atinduction,intraoperativelyor

postoperatively.

HowdoestheefficacyofondansetroncomparetootherantiemeticsforreducingPOVin

children?Ondansetronhashighefficacywhencomparedwithotherantiemetics.

Inametaanalysisexaminingstudiescomparingondansetronwithmetoclopramide

(6studies)ordroperidol(9studies)inchildrenundergoingdifferenttypesof

surgery,thepooledoddsratioshowedondansetrontobemoreeffectivethan

droperidol,OR0.49,andmetoclopramide,OR0.3345.

InasingleRCTof130children(45pergroup)ondansetronanddexamethasone

(1mg.kg1)werecomparedtoplacebo.Bothondansetronanddexamethasone

significantlyreducedtotalPOVandearlyPOVeffectively.However,inlatevomiting,

ondansetrondidnotreducePOVcomparedtoplacebowhereasdexamethasonewasclinicallyeffectivecomparedtobothplaceboandtoondansetron

51.

1+


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A OndansetronismoreclinicallyeffectivethandroperidolormetoclopramideinpreventingPOVinchildren.Ondansetronisequallyeffectivetodexamethasone

forearlyPOValthoughthelattermaybemoreeffectiveinreducinglatePOV.

Ondansetronshouldbeconsideredasafirstlinetreatmentinchildrenwithahigh

riskofPOV.Combinationtherapywithasecondagentmayimproveitsefficacy

(asdetailedbelow).

Tropisetron

TropisetronisaneffectiveantiemeticforPOVinchildren.Itdoesnotyethaveaproduct

licenseforuseinchildrenintheUK.

Twostudiesusingtropisetron0.10.2mg.kg1inchildrendemonstrateanoverall

oddsratioof0.15forPOVwithnocleardoserelatedresponse44.Onestudyof120

childrenfoundnodifferenceinoutcomewithearlyorlateadministrationof

tropisetron52.Anotherstudyexaminedtheadditionofdexamethasoneto

tropisetronandfoundthatoverallvomitingwasreducedfrom53%(tropisetron0.1

mg.kg1)to26%(tropisetron0.1mg.kg

1+dexamethasone0.5mg.kg

1)53.However,

thisreductionwasnotdetecteduntilafter4hourspostoperatively.

1+

A TropisetronisaneffectiveantiemeticinchildrenathighriskofPOVandthisefficacyisincreasedbytheadditionofdexamethasone.

AlthoughtropisteroniseffectiveinreducingPOVinchildren,itisnotlicensedfor

useinchildren.OndansetronshouldbeusedforreducingPOVinchildren.

Granisetron

Threestudiesoftheefficacyofgranisetroninchildrenundergoingtonsillectomy

demonstrateanoddsratioforPOVof0.11usingadoserangeof1080mcg.kg1.

Thereisnocleardoserelatedresponseasseenwithondansetron44.Furthermore

CochranemetaanalysissuggeststhattheeffectofgranisetrononreducingPOV

maybeoverestimatedbythesepapers.

1+

A GranisetronmaybeaneffectiveantiemeticforPOVinchildren.

MoreevidenceisrequiredontheefficacyofgranisetroninreducingPOVin

children.

Dolasetron

Inadosefindingstudyin204childrenundergoingdaycasesurgery,dolasetron350

mcg.kg

1

wasaseffectiveatpreventingPOVasondansetron100mcg.kg

1

.

54

Onestudyon150dexamethasonepretreatedchildrenundergoingtonsillectomyshowed

1+


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19anoddsratioof0.25forPOVinchildrengivendolasetron

55.

Acuteelectrocardiographicchangesinchildrenandadolescentsoccurvery

commonlywithdolasetron.(http://emc.medicines.org.uk)Thereisevidenceto

suggestthatacutechangesinQTcintervalaregreaterinchildrenthaninadults.

Individualcasesofsustainedsupraventricularandventriculararrhythmias,cardiacarrestandmyocardialinfarctionhavebeenreportedinchildrenandadolescents.

Theuseofdolasetroninchildrenandadolescentsunder18yearsoldis

contraindicated.

A Dolasetroniscontraindicatedforuseinchildrenandadolescentsunder18years

old.

DolasetroniscontraindicatedforpreventionofPOVinchildren.

Dexamethasone

Dexamethasonehasincreasinglybecomerecognisedasaneffectiveantiemeticinchildren

onitsownandincombinationwith5HT3antagonists.

WhatistheoptimaldoseofdexamethasoneforreducingPOVinchildren?

Todate,therehasbeenonesystematicreviewondexamethasoneforpreventionof

POVonmixedadultandpaediatricstudies56.Analysisofthe7paediatricstudies

wasnotreportedseparately.Dexamethasone1.01.5mg.kg1versusplacebo(3

trials)hadaNNTof10inpreventingearlyPOV(


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Anotherstudycomparedlowdosedexamethasone(50mcg.kg1to250mcg.kg

1)

andfoundasignificantreductioninPOVevenwithdosesassmallas50mcg.kg160.

TheNNTrangeforallgroupswas22.9.

Inanotherstudy.125childrenundergoingadenotonsillectomyortonsillectomy

wereenrolledinadoseescalatingstudyofdexamethasone:0.0625,0.125,0.25,

0.5,or1mg.kg1,maximumdose24mg61.Therewasnodoseescalationresponsetodexamethasoneforpreventingvomiting,reducingpain,shorteningtimetofirst

liquidintake,ortheincidenceofvoicechange.Thelowestdoseofdexamethasone

(0.0625mg.kg1)wasaseffectiveasthehighestdose(1.0mg.kg

1)forpreventing

POVorreducingtheincidenceofothersecondaryoutcomes.Theauthorsconclude

thereisnojustificationfortheuseofhighdosedexamethasonefortheprevention

ofPONVinthiscohortofchildren.

Severalreportsofacutetumourlysissyndromehavebeendescribedafter

dexamethasonehasbeengiventoasusceptiblepatientindosesusedinpreventing

POV.6264

TumourLysisSyndromeisapotentiallylethalconditionthatoccursparticularlyinhaematologicalmalignanciesaftertreatmentwithcytotoxic

therapies.Dexamethasonehasinducedacutetumourlysisinpatientswithnon

Hodgkinslymphoma62andacuteleukaemia.

6364

A DexamethasonegivenalonereducestheriskofPOVinchildren.ItappearstobeparticularlyeffectiveinpreventinglatePOV(>6hr).

Adoseofdexamethasone150mcg.kg1providesgoodreductioninPOVwithno

adverseeffects.Dosesaslowasdexamethasone62.5mcg.kg1

areefficaciousinreducingPOVinchildren.Dexamethasoneshouldnotbeusedinpatientsatrisk

oftumourlysissyndrome.

Metoclopramide

Metoclopramideindosesrangingfrom0.15mcg.kg1to0.25mcg.kg

1hasbeen

showntoreducePOVinchildreninsomestudiesonly6567.Overall,thereislittle

supportintheliteraturefortheuseofmetoclopramideasanantiemeticinchildren

fortheprophylaxisofpostoperativevomitinginthedosestested(usually0.25

mcg.kg

1

)

15,

45,

6872

.Theextrapyramidaleffectsassociatedwithmetoclopramidearemorecommonin

childrenandhaveoccurredindosesusedtotreatpostoperativevomiting.73

1+,

1++

A Metoclopramideindosesof0.25mcg.kg1orlessdoesnotreliablyreducePOVin

children.Furtherdoseresponsestudiesofmetoclopramidearerequiredtoseeif

improvedefficacyforpreventingPOVinchildrencanbeachievedathigherdoses.

Metoclopramideisnotareliableantiemeticinchildrenandisnotrecommended

forreducingPOVinchildren.Theroleofmetoclopramideinthetreatmentof

establishedpostoperativevomitingrequiresfurtherinvestigation.


21/35

21Prochlorperazine

Theantiemeticeffectofprochlorperazineinchildrenhasnotbeendetermined.

Sideeffectshavebeenreportedwhenchildrenhavebeengivenprochlorperazine74.

Thesearepredominantlyneurological,independentofdoseanddisappearedspontaneouslyafterdiscontinuationofthedrug.Impairedconsciousness,

dyskinesia,pyramidalsignsandhypertonuswerethemainneurological

manifestations.

4

D ThereisnoevidenceintheliteraturefortheefficacyofprochlorperazineforreducingPOVinchildren.

ProchlorperazineisnotrecommendedforpreventionofPOVinchildren.

CyclizineCyclizineisapiperazineantihistamineavailableoverthecounterandbyprescriptioninthe

UK,Canada,USandAustralia.InCanadatheuseofcyclizineforpatientsunder6yearsold

isofflabel.Ithasbeenreportedasadrugwithpotentialforabuse75.

Thereareonly2studiesontheuseofcyclizinefortreatingPOVinchildrenand

neitherhadpositivefindings7677.Ithasbeenconcludedthatthereisnodetectable

antiemeticeffectwithcyclizineandfurthermoretherewassignificantpainon

injection73.

1+

A ThereiscurrentlynoevidencetosupporttheuseofcyclizineforPOVinchildreneitherforprophylaxisorfortreatment.

CyclizineisnotrecommendedforreducingPOVinchildren.

Dimenhydrinate

Dimenhydrinateisthetheoclatesaltofdiphenhydramine.Dimenhydrinateisavailablein

Canada,theUSandAustraliabothoverthecounterandbyprescription.Itisnotavailable

intheUK.Itcanbegivenorally,intravenouslyandasasuppository.Itwassynthesized

withtheintentionofantagonizingthemoderatelysedativeeffectsofdiphenhydraminewiththemildlystimulanteffectsoftheophylline.Howeversedationanddrymouthand

otherantimuscarinicsideeffectsdooccur.Seriousadversereactionsappeartoberare

althoughitisaweaknessofbothpublishedRCTsandmetaanalysesthatthereislittle

documentationofsideeffects.

Twosystematicreviewsreportondimenhydrinate44,78.Inasystematicreviewand

metaanalysisofantiemeticprophylaxisforchildrenundergoingtonsillectomy,

dimenhydrinatewasnoteffectiveinthedosesstudied44.Inanothersystematic

review,theeffectivenessofdimenhydrinateforprophylaxisofpostoperative

nauseaandvomitingwasreportedinbothadultsandchildren78.Thepaediatric

studieswereanalysedasasubgroupandtheNNTforchildrenwasreportedas4.76

1+,

1++


22/35


forIV/IMadministrationand3.57forrectaladministrationofasingleequivalent

doseofdimenhydrinatehowevertheconfidenceintervalsarewide(2.5633.3and

1.9220).

InasmallRCTof100childrenundergoingreconstructivesurgeryforburns,

dimenhydrinate0.5mg.kg1wasfoundtobeasclinicallyeffectiveasondansetron

butmuchmorecosteffective

79

.Dimenhydrinate0.5mg.kg

1

hasalsobeenshowntobeeffectiveinstrabismussurgery80.Therearefewserioussideeffectsandthe

costbenefitratioisveryadvantageous.

A Insummary,thereisevidencetosupporttheuseofdimenhydrinateasprophylaxisinchildrenatmoderateorhighriskofpostoperativenauseaand

vomitingexceptfortonsillectomy.

Dimenhydrinate0.5mg.kg1maybeusedtoreducePOVinchildrenexceptfor

childrenundergoingtonsillectomy.

Therearenostudiesexaminingtheuseofdimenhydrinatetotreatpostoperativevomitingbutnonethelessitiscitedasrescuetherapyinonereviewarticleonperi

operativenauseaandvomitinginchildren81.

4

DDimenhydrinatehasbeenusedforrescuetherapyinestablishedPOVinchildren.

DimenhydrinatemaybeusefulforrescuetherapyinestablishedPOVinchildren.

CombinationTherapy

OndansetronandDexamethasone

Threerandomizedcontrolstudieshaveexaminedtheefficacyofondansetron

combinedwithdexamethasoneforpreventionofPOV8284.

Twolargestudiesdemonstratedthatondansetron50mcg.kg1combinedwith

dexamethasone150mcg.kg1wasmoreeffectiveatpreventingPOVinchildren

undergoingstrabismussurgerythanondansetron150mcg.kg1aloneor

dexamethasone150mcg.kg1alone

82,83.Astudyof193childrenundergoing

strabismussurgerycompareddexamethasone(150mcg.kg1)aloneto

dexamethasone(150mcg.kg1)plusondansetron(50mcg.kg1)82.Theadditionof

ondansetronreducedoverallvomitingfrom23%to5%.Astudyof200children

undergoingstrabismussurgerycomparedondansetron(150mcg.kg1,maximum

dose8mg)alonetodexamethasone(150mcg.kg1)plusondansetron(50mcg.kg

1)

83.TheincidenceofPOVwassignificantlylessinthecombinationgroup(9%)thanin

theondansetrononlygroup(28%).

Inanotherstudynodifferencebetweentreatmentswasdetectedbetweenseveral

combinationtreatmentgroupscontainingondansetronandarangeof

dexamethasonedosesandplacebo84.Thiswasattributedtotheparticularlylow

baselineincidenceofvomitingintheplacebogroup.

1+


23/35

23

A OndansetroncombinedwithdexamethasoneincreasestheeffectivenessinpreventingPOVinchildren.

InchildrenathighriskofPOV,combinationtherapyofondansetronand

dexamethasoneshouldbegiven.IVOndansetron50mcg.kg1andIV

dexamethasone150mcg.kg1shouldbegiventochildrenscheduledfor

adenotonsillectomyorstrabismussurgery.

Ondansetronandothercombinationantiemetictherapy

Ametaanalysisexaminingantiemeticcombinationtherapyincluded8paediatric

studies85.Althoughnoseparatedataoranalysiswaspresented,ondansetron

combinedwithdroperidolordexamethasonewasmoreeffectiveinpreventingPOV

thanondansetronalone.

1+

A OndansetronwhencombinedwithdroperidolordexamethasoneismoreeffectiveinpreventingPOVthanondansetronalone.

CombinationantiemetictherapyshouldbeusedforchildrenathighriskofPOV

orwheresingleagenttherapyhasfailedpreviously.Ondansetronand

dexamethasoneisthemosteffectivecombinationofantiemeticsforreducing

POVinchildrenandisrecommendedforsituationsathighriskofPOV.

TropisetronandDexamethasone

Inastudyof132children,tropisetron0.1mg.kg1alonewascomparedto

tropisetron0.1mg.kg1withdexamethasone0.5mg.kg

1forpreventionofPOVafter

tonsillectomy86.AdditionofdexamethasonereducedtheoverallincidenceofPOV

from53%to26%.Thisreductionwasnotevidentatlessthan4hours.

1+,1++

A Tropisetronplusdexamethasoneismoreeffectivethantropisetronaloneforthepreventionofpostoperativenauseaandvomitinginchildrenundergoing

tonsillectomy.

AlthoughIVtropisetronandIVdexamethasoneiseffectiveinreducingPOVin

children,tropisetronisnotlicensedforuseinchildren.Ondansetronand

dexamethasoneshouldbeusedforreducingPOVinchildrenathighriskofPOV.


24/35


B.AntiemeticsforTreatingEstablishedPostoperative

VomitinginChildren

TherearefewertrialsofefficacyofantiemeticsincontrollingestablishedPOVintherecoveryroominadultsandevenfewerinchildren

87,comparedtothe

multitudeoftrialsonprophylaxisofPOV.

Thereisonlyonetrialofasingledoseofondansetron(0.1mg.kg1)versusplacebo

formanagingestablishedPOVinchildrenwhohavenotreceivedprophylactic

therapy88:childrenexperiencingtwoemeticepisodeswithin2hofdiscontinuing

anaesthesiaweregivenIVondansetron0.1mg.kg1upto4mg(n=192)orplacebo

(n=183).Theproportionofchildrenwithnoemeticepisodesandnouseofrescue

medicationwassignificantlygreater(P


25/35

25

3.NonPharmacologicalTreatmentofPostoperative

VomitinginChildren

Avarietyofdifferentnonpharmacologicaloptionshavebeendescribedinordertoprevent

ortreatPONVinchildrenbutthenumberofpublicationsaswellaspatientnumbersand

studydesignareofteninsufficienttoallowforametaanalysisorstructuredreview(i.e.

typeofbandagingfollowingbatearsurgery90).Thus,thissectionwillonlyfocusonthe

differenttypesofstimulationoftheP6acupuncturepoint(acupuncture,acupressure,or

electrical/laserstimulation)thathasbeenreportedinchildren.

StimulationoftheP6AcupuncturePoint

Ametaanalysisin1999concludedvarioustypesofacustimulationinadultswere

equallyeffectivecomparedtoantiemeticdrugsinpreventingvomitingafter

surgeryandthatsuchnonpharmacologicalternativesweremoreeffectivethan

placeboinpreventingPONVintheearlypostoperativeperiod91.Nobenefitwas

foundwithinthepaediatricpopulationinthisreview.

Sincethentwofurtherreviewshavebeenpublishedthatincorporatemorerecent

publicationswithinthisfield.InalargeCochranereportfrom2004(updateofthe

1999metaanalysisabove,26trials,n=3,347)92acustimulationwasagainfoundto

beofbenefitinadultscomparedtocontrol.InthisCochranereport,acustimulationwasalsofoundtobeofbenefitinchildreninreducingtheincidenceofnauseaand

alsopointingtoaborderlinesignificantreductioninvomitingcomparedtosham

treatment.WhencomparedtoantiemeticdrugsusedforpreventionofPOV,

acustimulationappearedtobeequallyeffective.

RecentlyametaanalysisfocusingonchildrenincludedtwelveRCTs,mainly

performedinthecontextofhighrisksurgery(e.g.adenotonsillectomyor

strabismussurgery)93.Themetaanalysisshowedthatallacustimulationmodalities

reducedvomiting(RR=0.69,95%CI:0.590.80,p


26/35


4.SummaryofFindings&Recommendations

PatientFactorsassociatedwithahighriskofPOV:

SurgicalproceduresassociatedwithahighriskofPOV:


27/35

27AnaestheticfactorsaffectingtheincidenceofPOVinchildren:

SummaryofrecommendationsforpreventionofPOVinChildren:


28/35


SummaryofrecommendationsfortreatmentofestablishedPOVinChildren:


29/35

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apa guidelines on the prevention of postoperative vomiting in children

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