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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
DrLiamBrennan
ConsultantPaediatricAnaesthetist
AddenbrookesHospital
CambridgeUniversityHospitalsNHSFoundationTrust
HillsRd
CambridgeCB20QQ
DrSimonCourtman
ConsultantPaediatricAnaesthetist
PlymouthHospitalsNHSTrust
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
8/2/2019 APA Guidelines on the Prevention of Postoperative Vomiting in Children
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3DrNeilMorton
ConsultantPaediatricAnaesthetist
YorkhillChildrensHospital
Glasgow
SeniorLecturer
UniversityofGlasgow
MsJackiePope
Pharmacist
PlymouthHospitalsNHSTrust
DerrifordHospital
PlymouthPL68DH
DrScottJacobson
Resident
FamilyMedicine,
UniversityofNevada,
UnitedStatesofAmerica
FormerlyClinicalFellow
TheHospitalforSickChildren
Toronto
Canada
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GuidelinesonthePreventionofPostoperativeVomitinginChildren
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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GuidelinesonthePreventionofPostoperativeVomitinginChildren
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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GuidelinesonthePreventionofPostoperativeVomitinginChildren
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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GuidelinesonthePreventionofPostoperativeVomitinginChildren
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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GuidelinesonthePreventionofPostoperativeVomitinginChildren
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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GuidelinesonthePreventionofPostoperativeVomitinginChildren
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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GuidelinesonthePreventionofPostoperativeVomitinginChildren
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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GuidelinesonthePreventionofPostoperativeVomitinginChildren
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.
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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++
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GuidelinesonthePreventionofPostoperativeVomitinginChildren
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+
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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.
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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
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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
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4.SummaryofFindings&Recommendations
PatientFactorsassociatedwithahighriskofPOV:
SurgicalproceduresassociatedwithahighriskofPOV:
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27AnaestheticfactorsaffectingtheincidenceofPOVinchildren:
SummaryofrecommendationsforpreventionofPOVinChildren:
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SummaryofrecommendationsfortreatmentofestablishedPOVinChildren:
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