ReviewerNo.

1. ANAESTHETICS
1.1Generalanaestheticsandoxygen

Forproposedyellows:Arethesemedicinesforchildren?

Dothesemedicinesmeetapublichealth?

???Halothane

Aretheyregisteredforusein(allagecategoriesof)children?
UK

Inductionofanaesthesia
Byinhalationthroughspecificallycalibratedvaporiser
Child1218years
increasedgraduallyaccordingtoresponseto2%(upto4%inchildover16years)in
oxygenornitrousoxideoxygen

Maintenanceofanaesthesia
Byinhalationthroughspecificallycalibratedvaporiser
Child1month18years
0.52%
CDBNFC2006

1)Forinductionofanesthesia,aconcentrationof0.5%to2.5%innitrousoxide/oxygen
hasbeenusedinchildren(1to12yearsofage)(Naitoetal,1991b;Johannessonetal,
1987b;McAteeretal,1986b;Sigurdsson&Lindahl,1983a).Formaintenance,usual
concentrationshavebeen0.8%to2.5%innitrousoxide/oxygen(Naitoetal,1991b;
Johannessonetal,1987b;McAteeretal,1986b).
2)Theminimumalveolarconcentration(MAC)ofhalothanedecreaseswithincreasing
age(ProdInfoFluothane(R),1998a;AMADepartmentofDrugs,1994c;Dale&Brown,
1987d).MACvaluesininfantsandchildren3yearsofageare1.08%and0.9%,
respectively(ProdInfoFluothane(R),1998a).
3)Premedicationwithacombinationrectalsolutionofdiazepam0.5
milligram/kilogram,morphine0.15milligram/kilogram,andscopolamine0.01
milligram/kilogram(30to40minutespriortoinduction)maybeusefulinreducing
airwayreactionstohalothaneanesthesiainchildren(Johannessonetal,1987b).

DRUGDEXEvaluations
http://www.thomsonhc.com/hcs/librarian/ND_PR/Main/SBK/5/PFPUI/7wY1SX1UAf0IJ
/ND_PG/PRIH/CS/EA0A04/ND_T/HCS/ND_P/Main/DUPLICATIONSHIELDSYNC/53
57A7/ND_B/HCS/PFActionId/hcs.common.RetrieveDocumentCommon/DocId/1449/Co
ntentSetId/31/sectionId/pediatricDosageSection/SearchTerm/halothane%20/SearchOpti
on/BeginWith#ip3acessoem11/06/2007

Are there any unanswered/ unexpected clinical issues with respect to effectives or
safety?
Yes

Additionalcommentsifany:

Cautions
Avoidfordentalproceduresinthoseunder18yearsunlesstreatedinhospital(high
riskofarrhythmia);avoidinporphyria;
Hepaticimpairment
Avoidifhistoryofunexplainedpyrexiaorjaundicefollowingpreviousexposureto
halothane
CDBNFC2006

Halothaneisavolatileliquidanaesthetic.Itsadvantagesarethatitispotent,induction
issmooth,thevapourisnonirritant,andseldominducescoughingorbreathholding.
Despitetheseadvantages,however,halothaneismuchlesswidelyusedthan
previouslyowingtoitsassociationwithseverehepatotoxicity..
Halothanecausescardiorespiratorydepression.Respiratorydepressionresultsin
elevationofarterialcarbondioxidetensionandperhapsventriculararrhythmias.
Halothanealsodepressesthecardiacmusclefibresandmaycausebradycardia.The
resultisdiminishedcardiacoutputandfallofarterialpressure.Adrenaline
(epinephrine)infiltrationsshouldbeavoidedinchildrenanaesthetisedwithhalothane
asventriculararrhythmiasmayresult.
Halothaneproducesmoderatemusclerelaxation,butthismaybeinadequateformajor
abdominalsurgeryandspecificmusclerelaxantsarethenused.
CSMadvice(halothanehepatotoxicity)
Inapublicationonfindingsconfirmingthatseverehepatotoxicitycanfollowhalothane
anaesthesiatheCSMhasreportedthatthisoccursmorefrequentlyafterrepeated
exposurestohalothaneandhasahighmortality.Theriskofseverehepatotoxicity
appearstobeincreasedbyrepeatedexposureswithinashorttimeinterval,buteven
afteralonginterval(sometimesofseveralyears)susceptiblepatientshavebeen
reportedtodevelopjaundice.Sincethereisnoreliablewayofidentifyingsusceptible
patientstheCSMrecommendsthefollowingprecautionspriortouseofhalothane:
1. acarefulanaesthetichistoryshouldbetakentodeterminepreviousexposure
andpreviousreactionstohalothane;
2. repeatedexposuretohalothanewithinaperiodofatleast3monthsshouldbe
avoidedunlessthereareoverridingclinicalcircumstances;
3. ahistoryofunexplainedjaundiceorpyrexiainapatientfollowingexposureto
halothaneisanabsolutecontraindicationtoitsfutureuseinthatpatient.

CDBNFC2006


Dothesemedicinesmeetapublichealth?

.KetamineYes

Aretheyregisteredforusein(allagecategoriesof)children?Yes

I.M.:37mg/kg
I.V.:
Range:0,52mg/kg,usesmallerdoses(0,51mg/kg)forsedationforminorprocedures;
usualinductiondosage:12mg/kg
ContinuousI.V.infusion:Sedation520mcg/kg/minute;startatlowerdosagelistedand
titratetoeffect
Maintenance:supplementaldosesof1/3toofinitialdose.
PediatricDosageHandbookAmericanPharmaceuticalAssociation,2001/2002P.563
Administration
Parenteral:I.V.:Administerslower,donotexceeded0,5mg/kg/minute;donot
administerfasterthan60seconds;donotexceedfinalconcentrationof2mg/ml.
PediatricDosageHandbookAmericanPharmaceuticalAssociation,2001/2002P.563

Inductionandmaintenanceofanaesthesia(shortprocedures)
Byintravenousinjectionoveratleast60seconds
Neonate
12mg/kgproduces510minutesofsurgicalanaesthesia,adjustedaccordingto
response
Child1month12years
12mg/kgproduces510minutesofsurgicalanaesthesia,adjustedaccordingto
response
Child1218years
14.5mg/kg(usually2mg/kg)produces510minutesofsurgicalanaesthesia,adjusted
accordingtoresponse
Byintramuscularinjection
Neonate
4mg/kgusuallyproduces15minutesofsurgicalanaesthesia,adjustedaccordingto
response
Child1month18years
413mg/kg(4mg/kgsufficientforsomediagnosticprocedures),adjustedaccordingto
response;10mg/kgusuallyproduces1225minutesofsurgicalanaesthesia
Inductionandmaintenanceofanaesthesia(longerprocedures)
Bycontinuousintravenousinfusion

Neonate
initially0.52mg/kgfollowedbyacontinuousintravenousinfusionof
500micrograms/kg/houradjustedaccordingtoresponse;upto2mg/kg/hourmaybe
usedtoproducedeepanaesthesia
Child118years
initially0.52mg/kgfollowedbyacontinuousintravenousinfusionof0.6
2.7mg/kg/houradjustedaccordingtoresponse
CDBNFC2006

Arethereanyunanswered/unexpectedclinicalissueswithrespecttoeffectivesor
safety?Yes.

Inchildrenanesthetizedwithhalothane,ketaminehadadosedependenteffectonIOP
(intraocularpressure),with6mg/kgofthedrugcausingasmallincreaseinIOPat5to
10minutesand3mg/kgnotalteringtheIOP.Thehigherdoseofketaminealsowas
associatedwithanincreasedincidenceofpostoperativecomplications.
NagdeveNG,YaddanapudiS,PandavSS.Theeffectofdifferentdosesofketamineon
intraocularpressureinanesthetizedchildren.Journalofpediatricophthalmologyand
strabismus.43(4):21923,2006.

Ketamineisusedrarelynow.Ithasgoodanalgesicpropertiesatsubanaesthetic
dosage.Ithasparticularvalueinchildrenrequiringrepeatedanaesthesia;however,
recoveryisrelativelyslow.Thereisahighincidenceofextraneousmusclemovements;
alsocardiovascularstimulation,tachycardia,andraisedarterialpressuremayoccur.
Themaindisadvantageofketamineisthehighincidenceofhallucinations,
nightmares,andothertransientpsychoticeffects;thesecanbereducedwhendrugs
suchasdiazepamarealsoused.Ketamineiscontraindicatedinchildrenwith
hypertensionandisbestavoidedinthosepronetohallucinationsornightmares.Italso
hasabusepotentialandmayleadtodependance.

CDBNFC2006

Additionalcommentsifany:

RevisosistemticaCochrane:noone
Ensaioscontrolados:163
HeinzP,GeelhoedGC,WeeC,PascoeEM.Isatropineneededwithketaminesedation?
Aprospective,randomised,doubleblindstudy.Emergencymedicinejournal23(3):206
209,2006.
Publicationtype:JournalArticle;MulticenterStudy;RandomizedControlledTrial

AkbasM,TitizTA,ErtugrulF,AkbasH,MelikogluM.Comparisonoftheeffectof
ketamineaddedtobupivacaineandropivacaine,onstresshormonelevelsandthe
durationofcaudalanalgesia.ActaanaesthesiologicaScandinavica.49(10):15206,2005.

Publicationtype:JournalArticle;RandomizedControlledTrial
RobackMG,WathenJE,MacKenzieT,BajajLArandomized,controlledtrialofi.v.
versusi.m.ketamineforsedationofpediatricpatientsreceivingemergency
departmentorthopedicprocedures.48(5):60512,2006.
Publicationtype:JournalArticle;RandomizedControlledTrial

MarhoferP,KrennCG,PlchlW,WallnerT,GlaserC,KoinigH,FleischmannE,
HchtlA,SemsrothM.S(+)ketamineforcaudalblockinpaediatricanaesthesia.British
journalofanaesthesia.84(3)3415,2000.
Publicationtype:ClinicalTrial;JournalArticle;RandomizedControlledTrial

MurrayWB,YankelowitzSM,leRouxM,BesterHF.Preventionofposttonsillectomy
painwithanalgesicdosesofketamine.72(12):839842,1987.
Publicationtype:ClinicalTrial;ControlledClinicalTrial;JournalArticle

MarcusRJ,VictoriaBA,RushmanSC,ThompsonJP.Comparisonofketamineand
morphineforanalgesiaaftertonsillectomyinchildren.Britishjournalof
anaesthesia.84(6):73942,2000

AspinallRL,MayorA.Aprospectiverandomizedcontrolledstudyoftheefficacyof
ketamineforpostoperativepainreliefinchildrenafteradenotonsillectomy.Paediatric
anaesthesia.11(3)3336,2001.


Forgreens:Isthereanyreasonnottoendorsetheseasessentialmedicinesfor
children?

Nitrousoxide

Dothesemedicinesmeetapublichealth?Yes

Aretheyregisteredforusein(allagecategoriesof)children?Yes

Maintenanceoflightanaesthesia
Byinhalationusingsuitableanaestheticapparatus
Child1month18years
asamixturewith2530%oxygen
Analgesia
Byinhalationusingsuitableanaestheticapparatus
Childupto18years(butseenotesabove)
asamixturewith3050%oxygen,accordingtothepatientsneeds
CDBNF2006

Continuousinhalationofnitrousoxide30%withoxygen70%wasreportedeffectiveas
analgesicinchildrenpresentingtotheemergencyroomwithmildlacerations(Gamis
etal,1989).Inthisstudy,painperceptionwasdiminishedwiththeuseofthenitrous
oxidemixtureinchildrenmorethan8yearsofage;althoughatrendtowardadecease
inpainperceptionwasobservedinyoungerpatients(2to7years),thiswasnot
significant.Adverseeffectswerenotobservedduringadministration.Theuseofhigher
concentrationsofnitrousoxide(40%to50%)mayproducegreateranalgesiaandneed
tobeevaluatedinpediatricoutpatients.
GamisAS,KnappJF,GlenskiJA,etal:Nitrousoxideanalgesiainapediatric
emergencydepartment.AnnEmergMed1989;18:177181.

DRUGDEXEvaluations
http://www.thomsonhc.com/hcs/librarian/ND_PR/Main/SBK/6/PFPUI/CALDee1U1Bj1
B/ND_PG/PRIH/CS/2510F1/ND_T/HCS/ND_P/Main/DUPLICATIONSHIELDSYNC/44
D712/ND_B/HCS/PFActionId/hcs.common.RetrieveDocumentCommon/DocId/0769/Co
ntentSetId/31/sectionId/pediatricDosageSection/SearchTerm/nitrous%20oxide%20/Sear
chOption/BeginWith#ip3acessoem05/06/2007.

Aretheyanyunanswered/unexpectedclinicalissueswithrespecttoeffectivenessor
safety?No.

Aretherespecialrequirementsortrainingneededforsafe/effectiveuse?
Yes.

Additionalcommentsifany:

Nitrousoxidemustbegivenwithoxygen,otherwisehypoxiawilloccur.
Martindale33ed.,P.1265

Theuseofhighdosesofopioidssuchasfentanylwithnitrousoxidemayresultina
dropinheartrateandcardiacoutput.
Combineduseofnitrousoxideandmethotrexatemayincreasethesideeffectsof
methotrexatetherapy
Martindale33ed.,P.1265

Nitrousoxideisusedformaintenanceofanaesthesiaand,insubanaesthetic
concentrations,foranalgesia.Foranaesthesiaitiscommonlyusedinaconcentrationof
50to70%inoxygenaspartofabalancedtechniqueinassociationwithother
inhalationalorintravenousagents.Nitrousoxideisunsatisfactoryasasoleanaesthetic
owingtolackofpotency,butisusefulaspartofacombinationofdrugssinceitallows
asignificantreductionindosage.

Amixtureofnitrousoxideandoxygencontaining50%ofeachgas(Entonox,
Equanox)isusedtoproduceanalgesiawithoutlossofconsciousness.Self
administrationusingademandvalvemaybeusedinchildrenwhoareabletoself
regulatetheirintake(usuallyover5yearsofage)forpainfuldressingchanges,asan
aidtopostoperativephysiotherapy,forwounddebridementandinemergency
ambulances.
Nitrousoxidemayhaveadeleteriouseffectifusedinchildrenwithanaircontaining
closedspacesincenitrousoxidediffusesintosuchaspacewitharesultingincreasein
pressure.Thiseffectmaybedangerousinthepresenceofapneumothoraxwhichmay
enlargetocompromiserespiration.

Specialcareisneededtoavoidhypoxiaifananaestheticmachineisbeingused;
machinesshouldincorporateanantihypoxiadevice.Exposureofchildrentonitrous
oxideforprolongedperiods,eitherbycontinuousorbyintermittentadministration,
mayresultinmegaloblasticanaemiaowingtointerferencewiththeactionofvitamin
B12.Forthesamereason,exposureoftheatrestafftonitrousoxideshouldbe
minimised.Depressionofwhitecellformationmayalsooccur.
CDBNF2006

ActionproposedfortheCommitteetotake:Toapprove

Forgreens:Isthereanyreasonnottoendorsetheseasessentialmedicinesfor
children?

Oxygen

Dothesemedicinesmeetapublichealth?Yes

Aretheyregisteredforusein(allagecategoriesof)children?Yes

Itisusedasadiluentofgaseousanaesthetics.
Martindale33ed.,P.1200
Seechecklistnitrousoxide.

Aretheyanyunanswered/unexpectedclinicalissueswithrespecttoeffectivenessor
safety?No.

Aretherespecialrequirementsortrainingneededforsafe/effectiveuse?Yes.

Additionalcommentsifany:

Anyfireorsparkishighlydangerousinthepresenceofincreasedoxygen
concentrationsespeciallywhenoxygenisusedunderpressure.

Metalcylinderscontainingoxygenshouldbefittedwithareducingvalvebywhichthe
rateofflowcanbecontrolled.Itisimportantthatthereducingvalveshouldbefree
fromalltracesofoilorgrease,asotherwiseaviolentexplosionmayoccur.
Combustiblematerialsoakedinliquidoxygenispotentiallyexplosiveandthelow
temperatureofliquidoxygenmaycauseunsuitableequipmenttobecomebrittleand
crack.Liquidoxygenshouldnotbeallowedtocomeintocontactwiththeskinasit
producessevere`coldburns.

Oxygenintendedforaviationormountainrescuemusthaveasufficientlylow
moisturecontenttoavoidblockingofvalvesbyiceonfreezing.

Highconcentrationsofoxygenshouldbeavoidedinpatientswhoserespirationis
dependentuponhypoxicdrive,otherwisecarbondioxideretentionandrespiratory
depressionmayensue.

Martindale33ed.,P.1200

ActionproposedfortheCommitteetotake:Toapprove


Forgreens:Isthereanyreasonnottoendorsetheseasessentialmedicinesfor
children?

Thiopental

1.1Generalanaestheticsandoxygen

Dothesemedicinesmeetapublichealth?Yes

Aretheyregisteredforusein(allagecategoriesof)children?Yes

Aretheyanyunanswered/unexpectedclinicalissueswithrespecttoeffectivenessor
safety?No.

Aretherespecialrequirementsortrainingneededforsafe/effectiveuse?

Intravenousinjectionsarenormallygivenasa2.5%solution;theBNFCrecommends
thatintravenousinfusionsaregivenasa0.25%solution.
MARTINDALETheCompleteDrugReference
http://www.thomsonhc.com/hcs/librarian/ND_PR/Main/SBK/1/PFPUI/TR1apL21U7fz3
W/ND_PG/PRIH/CS/550441/ND_T/HCS/ND_P/Main/DUPLICATIONSHIELDSYNC/9
18459/ND_B/HCS/PFActionId/hcs.common.RetrieveDocumentCommon/DocId/3124
b/ContentSetId/30/SearchTerm/thiopental/SearchOption/BeginWith#secN66508acesso
em06/06/2007

Administration
Forintravenousinjection,dilutetoaconcentrationof25mg/mLwithWaterfor
Injections,andgiveoveratleast1015seconds;forintravenousinfusiondilutetoa
concentrationof2.5mg/mLwithSodiumChloride0.9%
CDBNFC2006

Additionalcommentsifany:

Fortheinductionofanaesthesiainchildren,UKlicensedproductinformation
recommendsthatthiopentalsodiumisgivenbyslowintravenousinjection(over10to
15seconds)inadoseof2to7mg/kg;thedosemayberepeatedafter1minute.
MARTINDALETheCompleteDrugReference
http://www.thomsonhc.com/hcs/librarian/ND_PR/Main/SBK/1/PFPUI/TR1apL21U7fz3
W/ND_PG/PRIH/CS/550441/ND_T/HCS/ND_P/Main/DUPLICATIONSHIELDSYNC/9
18459/ND_B/HCS/PFActionId/hcs.common.RetrieveDocumentCommon/DocId/3124
b/ContentSetId/30/SearchTerm/thiopental/SearchOption/BeginWith#secN66508
acessoem06/06/2007

Inductionanesthesia:I.V.:
Neonates:34mg/kg
Infants:58mg/kg

Children112years:56mg/kg
Maintenanceanesthesia:I.V.
Children:1mg/kg
PediatricDosageHandbookAmericanPharmaceuticalAssociation,2001/2002P.952

Inductionofanaesthesia
Byslowintravenousinjection
Neonate
4mg/kgrepeatedafter1minuteifnecessary
Child1month18years
4mg/kg(max.150mg)repeatedafter1minuteifnecessary
CDBNFC2006

Barbiturateanaestheticsarecontraindicatedwhenthereisdyspnoeaorrespiratory
obstructionsuchasinacutesevereasthmaorwhenmaintenanceofanairwaycannot
beguaranteed.

Barbiturateanaestheticsshouldbeusedwithcautioninshockanddehydration,
hypovolaemia,severeanaemia,hyperkalaemia,toxaemia,myastheniagravis,
myxoedemaandothermetabolicdisorders,orinsevererenaldisease.Cautionisalso
requiredinpatientswithcardiovasculardisease,musculardystrophies,adrenocortical
insufficiency,orwithincreasedintracranialpressure.Reduceddosesarerequiredin
theelderlyandinseverehepaticdisease.

Barbituratesincludingthiopentalsodiumhavebeenassociatedwithacuteattacksof
porphyriaandareconsideredunsafeinporphyricpatients.

Martindale33ed.,P.1269

Cautions
Cardiovasculardisease;reconstitutedsolutionishighlyalkalineextravasationcauses
tissuenecrosisandseverepain;avoidintraarterialinjection.

Hepaticimpairment
reduceinductiondoseinsevereliverdisease

Contraindications
PorphyriA;myotonicdystrophy

Breastfeeding
presentinmilkmanufactureradvisesavoid
CDBNFC2006.

ActionproposedfortheCommitteetotake:Toapprove