Andersons pediatric cardiology 232
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affectsalmost10%ofchronicallytreatedpatients.Themostserious
complicationinadultsispulmonarytoxicity,whichcanrarelyoccurearlyafter
treatmentinitiation.Amiodaroneshouldbeimmediatelydiscontinuedifthe
motherdevelopspulmonaryinflammatorychanges.Anonproductivecoughand
dyspneaarethemainsymptomsofaffectedindividualsatpresentation.Pleuritic
pain,weightloss,fever,andmalaisecanalsooccur.AswithotherclassIII
agents,thereisariskoftorsadedepointes,whichcanbeminimizedbyavoiding
excessiveQTcprolongation.Adversefetaleffectsattributedtotheuseof
amiodaroneincludetransientcongenitalthyroiddysfunction,growthretardation,
andmildneurodevelopmentalabnormalities.34,35,42–44
DirectFetalTreatment.
Directfetaltreatmentshouldbeconsideredifotherlessinvasivetreatment
measureshavefailedorifimmediatetreatmentisrequiredtoterminateorslow
downalife-threateningSVA.Inthepresenceoffetalhydrops,thetransplacental
transferofmostantiarrhythmicmedicationishamperedandtherapeuticlevelsof
drugsmaynotbereachedevenwithhighmaternaldoses.Toovercomethis
problem,repeatedintravenous,intramuscular,andintraperitonealfetalinjections
ofamiodaroneand/ordigoxin,inadditiontotransplacentalmaternalmedication,
havebeensuccessfullyusedtodealwithtreatment-refractoryfetalAVRT,
althoughfetaldeathswiththeuseofthisstrategyhaveoccurred.10,19,36,45,46
Amiodaroneseemstobepredestinedfordirectuse,bothbecauseofitsefficiency
andlonghalf-life,thuslimitingthenumberofinvasivefetalproceduresrequired
tomaintaintherapeuticlevels.Directintravenousadenosinemayinstantly
terminateAVRT,47–49butbecauseofitsshortdurationofaction,itshouldbe
administeredincombinationwithalonger-actingantiarrhythmicagent.
OtherAntiarrhythmicAgents.
Otherantiarrhythmicagentssuchasverapamil,procainamide,andquinidineare
notrecommendedforprenataltherapy11becauseofthepotentialrisksofsevere
sideeffectsand/orinsufficientantiarrhythmicaction.
TreatmentResults
Retrospectivecaseseriesreportinconsistentsuccessratesforallantiarrhythmic
medicationintreatingfetalSVA,whichmaybeexplained,amongotherthings,
bydifferencesinthedefinitionofatreatmentsuccessandindiseaseseverity
betweenpatientcohorts.Withthiscaveatinmind,instudiesusingoraldigoxin
asfirst-lineagent,inuterocardioversionhasbeenreportedin50%to100%of
fetuseswithSVAwithouthydrops,butin40%orlessoffetuseswithSVAand
hydrops.7,9,10,18,28,29,50Flecainidehasresultedinsinusrhythmin58%to100%
ofSVAcaseswithouthydropsandin43%to86%ofthosewith
hydrops.17,18,26,28–30,34Sotalolmonotherapyhasbeensuccessfulin40%to
100%ofSVAcaseswithouthydropsandin50%to67%ofthosewith
hydrops.6,21,22,25,27Whenusedtotreatdrug-refractorySVT,transplacental
amiodaronealoneorincombinationwithdigoxinwasassociatedwitha71%
rateofinuterocardioversion.34,35Similarorhighercardioversionratesto
amiodaronewereobtainedwithcombinationtreatmentofdigoxinplus
flecainide,23,33sotalolplusdigoxin,21,25andsotalolplusflecainide.27Resultsof
directfetaldrugtherapyarelargelyunavailable.
Althoughthesepublisheddatasuggestsimilartreatmentresultswiththe
currentlyusedantiarrhythmicagents,drug-specificdifferencesintheirmodesof
actionandpharmacokineticslikelypredeterminethepotentialofacompoundin
terminatingand,oncethishasbeenachieved,suppressingSVArecurrences.In
theretrospectivemulticenterstudybyJaeggietal.5comparingnonrandomized
first-linetreatmentwithoneofthreeagents―digoxin,flecainide,orsotalol―the
fetalresponsetoantiarrhythmictherapywassignificantlyinfluencedbyfetal
hemodynamics,arrhythmiamechanism,andthechoiceofdrugmanagement.
Slowercardioversionratestoanormalrhythmwerefoundtobesignificantly
associatedwith(1)apersistenttachycardiapattern(hazardratio[HR],3.1;P<
.001)duringtheinitialfetalechocardiogramwhencomparedwithintermittent
arrhythmia;(2)fetalhydrops(HR,1.8;P=.04),presumablyduetoincomplete
passageofmaternallyadministeredantiarrhythmicdrugsacrosstheplacenta;(3)
AF(HR,2.0;P=.005)whencomparedwithotherformsofSVA;and(4)the
choiceoffirst-linetherapy(Fig.9.1).Sotalolwasassociatedwithhigherratesof
prenatalAFterminationthandigoxin(HR,5.4;P=.05)orflecainide(HR,7.4;
P=.03).ThemediantimetoconversionofAFcaseswasalmost2weekswith
sotalol,whereasthiswasnotachievedwithdigoxinorflecainidebeforedelivery.
Flecainide(HR,2.1;P=.02)ordigoxin(HR,2.9;P=.01)wereassociatedwith
ahigherrateofconversionoffetalSVAotherthanAFtoanormalrhythm
comparedwithsotalol.ThemediantimetocardioversionofAVRT,AET,and
PJRTwas3dayswithdigoxin,4dayswithflecainide,but12dayswithsotalol.
IftheSVApersisted,tachycardiaratesdeclinedmorewithflecainideand
digoxin.Finally,therapyinitiationwithdigoxin,flecainide,orsotalolas
monotherapyappearedsafeunlessfetalhydropswaspresent,whichwas
associatedwith21%perinatalmortality.Thisledtothestudy'srecommendation
toconsiderdrugcombinations(e.g.,flecainideplusdigoxinforAVRT;sotalol
plusdigoxinforAF)asfirst-linetreatmentwhenrapidtachycardiacontrol
becomesamatterofurgency.
