Andersons pediatric cardiology 1790
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thereareafewstudiesdemonstratingamorenormalrateresponseandanormal
maximalconsumptionofoxygen.87,92,95Thelargestandmostrecentstudyof
serialexercisetestsinchildrendemonstratedbetterexercisecapacityassociated
withyoungerageattransplantation,especiallyforinfants;apositiverelationship
betweenpeakheartrateandtimesubsequenttotransplantation;goodexercise
capacitywithameanmaximumoxygenconsumptionof30mL/kgperminuteat
ameanof5.5yearsaftertransplantation;andapossibleassociationwithchanges
onserialstudiesandthepresenceofCAV.95
Infections
Infectionisaconcerninallcasesofsolidorgantransplantationandrepresentsa
significantcauseofmorbidityandmortality.96Riskfactorsincludeearlierageat
transplant,discrepancybetweendonorandrecipientviralstatus(e.g.,aCMVnegativerecipientisathighriskofthediseaseifheorshereceivedaCMVpositivedonor),anddegreeofimmunosuppression.AreportfromISHLT
identifiedinfectionasbeingresponsiblefor6%ofdeathsoccurringafter
transplant.2Infectionwasalsoasignificantcauseofhospitalization,particularly
inthefirstposttransplantyear(19%),althoughby5yearsposttransplantthishad
fallento10%.2
Infectionsthathaverequiredhospitalizationorintravenoustherapyweredue
tobacterialinfectionsin43%ofcases.97Staphylococcusaureus,Klebsiella
species,andEscherichiacoliarecommonpathogensduringallperiodsafter
transplantation.Beyondtheimmediateposttransplantperiod,Streptococcus
pneumoniae,Haemophilusinfluenzae,Moraxellacatarrhalis,andSalmonella
speciesarecommoncommunity-acquiredinfections,whereasopportunistic
pathogensandmycobacteriaarerare.Viralinfectionsarealsocommon,
includingrespiratoryviruses(adenovirus,influenza)andnorovirus.The
herpesvirusgroup(varicellazoster,herpessimplex,cytomegalovirus,EpsteinBarrvirus[EBV]andhumanherpesvirustype6)areofparticularimportance.
Theymaycauseprimaryorsecondaryinfection(reactivationoflatentinfection),
andsuchinfectionsmaybeasymptomaticorlife-threateningtothe
immunocompromisedhost.EBVinparticular,maycauseasymptomaticprimary
infectionandisusuallythedriverbehindthedevelopmentofPTLD.Other
viruses—suchashumanpapillomavirus(warts)andmolluscumcontagiosum—
aremoreofanuisance.Pneumocystisjirovecii,afungus-likeorganism,isalsoa
concern,particularlyintheearlyposttransplantphase.
ProphylaxisforCMVandP.jiroveciiwithantimicrobialagentsisusually
employedinthemostimmunosuppressedtimeperiod(thefirst3to6months
posttransplant)toeitherdeferorpreventinfections.98,99Childrenwhohave
recurrentrespiratoryinfectionsmaybenefitfromprophylacticantibioticsand
regularchestphysiotherapytopreventthedevelopmentofbronchiectasis.100
Mostchildrenundergoingtransplantationhavenotfinishedtheirroutine
scheduleofimmunizations.Titersshouldbecheckedpriortotransplantation.
Effortsshouldbemadetoimmunizewithasmanyvaccinationsasfeasibleand
developmentallyappropriatepriortotransplantation.Thisisparticularly
importantwithvaccinesthatincorporateliveviruses.Vaccinationschedules
shouldberesumedapproximately6monthsaftertransplantation.Giventhe
suppressionoftheimmunesystemandthevariableresponsestoforeign
antigens,antibodytitersshouldbecheckedaftervaccinationinordertoensure
anappropriateresponse.Ingeneral,liveviralvaccinesareavoided
posttransplant,althoughthereisincreasingevidenceandexperienceoftheirsafe
useincarefullyselectedpatients.101
RenalFunction
Manypatientshavesomeimpairmentofrenalfunctionpriortotransplantation.
Inthepatientwithcongenitalheartdisease,thismaybeduetotheeffectsof
previouscardiacsurgeryorcyanosis.Particularlyinthesingle-ventricle
populationfollowingtheFontanprocedure,systemicvenouspressuremaybe
chronicallyelevated.Inthosewithcardiomyopathy,inadequatecardiacoutputis
themostcommoncauseofimpairedrenalfunction,butthismayalsobedueto
emboliinpatientsonmechanicalcirculatorysupport.Renalfunctionisoften
furthercompromisedintheperitransplantperiod,asepisodesofhemodynamic
instabilityarenotuncommon.AnanalysisfromtheUnitedNetworkforOrgan
Sharingdatabasedemonstratesthatdialysisinthepre-andposttransplantperiod
iscommon(7%ofrecipients)andismorelikelywithECMO,ventilator,
inotropesupport,infection,congenitalheartdisease,andamedicalcondition
(intensivecareunithome).102The30-daysurvivalwaslowerinthedialysis
group(72%vs.95%);however,dialysishadnoeffectonlatesurvival
conditionalonsurvivingto6months.
Posttransplant,calcineurininhibitorsarenephrotoxic.103TheISHLTregistry
reportsthefreedomfromrenalreplacementtherapy(definedasdialysisor
transplant)as89%at20yearsforthosetransplantedasinfants.Otheragegroups
faredslightlyworse.2Recentlystrategieshaveutilizedmammaliantargetof
rapamycininhibitors—eithercompletelyreplacingthecalcineurininhibitoror
allowingareductionindose.2Thesestrategiesappeartobesuccessfulprovided
thatrenalfunctionisonlymoderatelyreducedandthemammaliantargetof
rapamycininhibitorsaretoleratedbythepatients.104
LymphoproliferativeDisorders
Malignanciesareanotherimportantcauseofmorbidityandmortalityafter
transplantation(seeTables67.3and67.4;Fig.67.30).Theycanoccurasnew
events,beareactivationofpreviouscancer,orresultfromchronicviral
infections,withthelatterbeingmostimportantinchildren.Thereportedoverall
incidenceofmalignancyishighlyvariableandrelatedbothtovariationin
definitionandwhetherornotmalignancyisreportedinatime-dependent
manner.Thereportedtime-unadjustedoverallincidenceofthemostcommon
malignancyinchildhood,PTLD,rangesfrom3%to9%.2,15,105Asthereisa
temporalrelationshiptoincidence,therearereportsofanincidenceashighas
23%to28%insurvivorsmorethan10yearsaftertransplantation.16,106Survival
fromthePHTSregistrywas95%at1month,75%at1year,and67%at5
years.15
Table67.4
CumulativePrevalenceofMalignancyinChildrenAfterHeart
Transplantation(January1994toJune2014)
Malignancy/Type
Nomalignancy
Malignancy(alltypescombined)
Malignancytype
Lymph
Other
Skin
Typenotreported
1-YearSurvivors
5451(98.4%)
88(1.9%)
5-YearSurvivors
3072(95.3%)
151(4.7%)
10-YearSurvivors
1281(90.5%)
134(9.5%)
80
8
0
0
143
10
1
0
128
9
2
0
DatafromtheregistryoftheInternationalSocietyofHeartandLungTransplantation.JHeart
LungTransplant.2016:35(10):1185–1195.
