Andersons pediatric cardiology 1399
Bạn đang xem bản rút gọn của tài liệu. Xem và tải ngay bản đầy đủ của tài liệu tại đây (89.64 KB, 3 trang )
Treatment
Treatmentofthediseaseinthefirstweeksafteronsetisaimedatloweringfever,
reducinginflammationandshearstressinthearterialwall,andpreventing
thrombosis.Toreduceshearstress,childrenwhoareprofoundlyanemicandin
whomcoronaryaneurysmsaredevelopingshouldundergotransfusionofred
bloodcells,ideallytoachieveahematocritofatleast30%,andβ-blockers
shouldbeadministeredtoreducemyocardialconsumptionofoxygen.Among
patientswithaneurysms,thepreventionand,ifneeded,treatmentofcoronary
thrombosisarekeycomponentsoftherapy.Patientswithcoronaryarterystenosis
orocclusionandevidenceofreversibleischemiaarecandidatesfor
interventionalcatheterizationandsurgicalprocedures.Specifictherapiesare
detailedlaterinthischapter.
Aspirin
AspirinisusedintheacutetreatmentofKawasakidiseaseforits
antiinflammatoryandantiplateleteffects.Thereisnoconsensusontheoptimal
doseofaspirinaswellassignificantvariationinpractice.RecentAmerican
HeartAssociationguidelinessuggestthatitisreasonabletoadminister
moderate-(30to50mg/kgperday)tohigh-dose(80to100mg/kgperday)until
thepatientisafebrileandthentolowerthedoseto3to5mg/kgperdayforits
antiplateleteffects.2Amulticenterretrospectivestudyshowedthatlow-dose
aspirininnotinferiortohigh-doseaspirinatthetimeofinitialdiagnosisfor
reducingtheriskofcoronaryarteryabnormalities;thisisinlinewithprior
studiesshowingnoroleinthepreventionofcoronaryartery
complications.127,128Aspirininlowdosesiscontinuedforapproximately6
weeksandthendiscontinuedinpatientswithoutcoronaryarteryaneurysms.In
childrenwithcoronaryarteryabnormalities,aspiriniscontinuedindefinitelyat
lowdosesandmaybeusedtogetherwithotherantithrombotictherapiessuchas
clopidogrelorwarfarin.Becauseibuprofenantagonizestheinhibitoryeffectof
aspirinonplatelets,sustainedtherapywithibuprofenshouldbeavoidedin
childrenwhoaretakingaspirinforprophylaxisofcoronaryarterythrombosis.129
Reyesyndromehasbeenreportedinchildrenwiththediseasewhoaretaking
aspirininhighdoses.130–132Althoughthissyndromehasnotbeenassociated
withuseofaspirininlowdoses,annualvaccinationagainstinfluenzais
recommendedforallchildrenonchronictreatmentwithaspirin.Whenachild
medicatedonachronicbasiswithaspirindevelopsaflu-likeillness,aspirin
shouldbewithheldtransientlyand,ifnecessary,anotherantiplateletmedication,
suchasclopidogrel,shouldbesubstituteduntilresolutionoftheillness.
IntravenousImmunoglobulin
Controlofinflammationdecreasesthelikelihoodofaneurysmformationandis
themostimportantaimoftherapyintheacutephaseofillness.Amongthe
armamentariumofantiinflammatoryagentsthathavebeenused,onlyIVIGin
highdoseshasbeendemonstratedtobeeffectiveinmultiplerandomized
multicentertrialswithblindedechointerpretation.133–135Whenadministeredin
thefirst10days,IVIGreducestheprevalenceofaneurysmsapproximately
fivefold,tolessthan5%.TreatmentwithIVIGisalsobeneficialforchildren
beyondthe10thdayofillnessinwhomfeverpersistsorwhohavecoronary
arteryabnormalitiestogetherwithpersistentclinicalandlaboratoryevidenceof
inflammation.136PatientswithrecurrentKawasakidisease,definedasarepeat
episodeaftercompleteresolutionofthepreviousepisode,shouldalsoreceive
standardtherapywithaspirinandIVIG.Thestandarddosageis2g/kg
administeredover8to12hours.133,137Studiescomparingtheefficacyof
differentimmuneglobulinproductshavebeenconflicting.137–139
Inpatientswhopresentwithdiminishedleftventricularfunction,theagent
shouldbeadministeredmoreslowlybecauseoftheconsiderablevolumeload.
Coombs-positivehemolyticanemiaisacomplicationofIVIG,especiallyin
patientswiththeA,B,orABbloodgrouptype.140,141Asepticmeningitiscan
alsooccurandresolvesquicklywithnoneurologicsequelae.142Immunization
formeasles,mumps,andvaricellashouldbedeferredfor11monthsafterIVIG
administration.143
OtherTherapies
WhereasthemaintreatmentintheacutephaseincludesaspirinandIVIG,some
patientsathigherriskmaybenefitfromprimaryadjunctivetreatment.Thereare
multipleJapaneserisk-scoringsystemstoidentifypatientsathigherrisksof
IVIGresistanceandcoronaryarterycomplications,144–146However,theirlow
sensitivityinNorthAmericanpopulationslimitstheiruse.147
Corticosteroidsarethemainstayoftherapyformanychildhoodvasculitides,
althoughtheiruseinthetreatmentofpatientswithKawasakidiseasehasbeen
morecontroversial.Theuseofpulsed-doseintravenousmethylprednisolonedid
notimproveoutcomeinarandomizedmulticenterplacebo-controlledtrial
performedinNorthAmerica.148However,studiesinJapanhaveshown
improvedcoronaryoutcomeswhensingle-dosemethylprednisolonewas
administeredtohigh-riskpatients.146,149–150Moreover,theuseoforalsteroids
withaslowtaperwasshowntobebeneficialintherandomizedcontrolledtrial
toassessimmunoglobulinplussteroidefficacyforKawasakidisease(RAISE
study)inhigh-riskpatients,withadecreasedincidenceofcoronaryartery
abnormalitiesandtreatmentresistance,lowercoronaryarteryz-scores,andmore
rapidresolutionoffeveraswellasadeclineininflammatorymarkers.151Thus
thechallengeinnon-Japanesepopulationsistoidentifypatientswhomight
benefitfrommoreaggressivetherapy.
Infliximab,achimericmonoclonalantibodytoTNF-α,wasstudiedfor
intensificationofinitialtreatment.152Althoughitshortenedthenumberofdays
offeverandinflammatoryparametersnormalizedmorerapidly,itfailedto
decreasetherateofIVIGresistance,whichwastheprimaryoutcomeofthe
study.Trialsusingetanerceptfortreatmentintensificationareongoing.153
AdditionalTherapyforPatientsWithIntravenous
ImmunoglobulinResistance
Approximately10%to20%ofpatientswithKawasakidiseaseareresistantto
intravenousimmunoglobulins,definedaspersistentorrecurrentfeveratleast36
hoursaftertheendoftheirIVIGinfusionwithoutotherexplanation.154Patients
withresistancetoIVIGareatincreasedriskofcoronaryarterycomplications
andthususuallywarrantretreatment.155Meta-analyseshavedemonstrateda
dose-responseeffectofIVIG156;thusexpertsrecommendasecondinfusionof
IVIG.
Corticosteroidshavealsobeenusedtotreatpatientswhofailedtorespondto
initialtherapy.Retrospectivestudiesandcaseseriessuggestthattreatmentwith
steroidsimprovesfeverandtheinflammatoryresponse157–159;however,notall
studieshaveshownimprovementincoronaryarteryoutcome.157,158,160Both
pulseintravenousmethylprednisone(30mg/kgperday)157,158,160and
intravenousprednisolone(2mg/kgperday)wereused,159withnoclinicaltrials
