www.jped.com.br
REVIEW
ARTICLE
Neonatal
and
pediatric
extracorporeal
membrane
oxygenation
in
developing
Latin
American
countries
夽
Javier
Kattan
a,∗,
Álvaro
González
a,
Andrés
Castillo
b,
Luiz
Fernando
Caneo
caPontificiaUniversidadCatólicadeChile,EscueladeMedicina,DepartamentodeNeonatología,Santiago,Chile
bPontificiaUniversidadCatólicadeChile,EscueladeMedicina,UnidaddeCuidadosIntensivosPediátricos,Santiago,Chile
cUniversidadedeSãoPaulo(USP),FaculdadedeMedicina,CirurgiaCardiovascularPediátrica,SãoPaulo,SP,Brazil
Received15September2016;accepted11October2016 Availableonline26December2016
KEYWORDS Extracorporeal membrane oxygenation; ECMO;
Respiratoryfailure; Cardiacfailure; Pulmonary hypertension; ELSO
Abstract
Objective: Toreviewtheprinciplesofneonatal-pediatricextracorporealmembrane oxygen-ationtherapy,prognosis,anditsestablishmentinlimitedresource-limitedcountriesinLatino America.
Sources: ThePubMeddatabasewasexploredfrom1985uptothepresent,selectingfrom highly-indexedand leading LatinAmerican journals,andExtracorporeal LifeSupport Organization reports.
Summaryofthefindings: Extracorporeal membrane oxygenation provides ‘‘time’’ for pul-monaryandcardiacrestandforrecovery.Itisusedintheneonatal-pediatricfieldasarescue therapyfor morethan1300patients withrespiratory failureandaround 1000patients with cardiacdiseasesperyear.Thebestresultsinshort-andlong-termsurvivalareamongpatients withisolatedrespiratorydiseases,currentlyestablishedasastandardtherapyinreferral cen-tersforhigh-riskpatients.Thefirstneonatal/pediatricextracorporealmembraneoxygenation PrograminLatinAmericawasestablishedinChilein2003,whichwasalsothefirstprogramin LatinAmericatoaffiliatewiththeExtracorporealLifeSupportOrganization.New extracorpo-realmembraneoxygenationprogramshavebeendevelopedinrecentyearsinreferralcenters inArgentina,Colombia,Brazil,Mexico,Perú,CostaRica,andChile,whicharecurrentlyfunding theLatinAmericanExtracorporealLifeSupportOrganizationchapter.
Conclusions: Thebestresultsinshort-andlong-termsurvivalareinpatientswithisolated respi-ratorydiseases.Todayextracorporealmembraneoxygenationtherapyisastandardtherapyin some LatinAmerican referralcenters.Itishopedthatthesenewextracorporealmembrane oxygenation centers will have a positive impact on the survival ofnewborns and children
夽
Pleasecitethisarticleas:KattanJ,GonzálezÁ,CastilloA,CaneoLF.Neonatalandpediatricextracorporealmembraneoxygenationin developingLatinAmericancountries.JPediatr(RioJ).2017;93:120---9.
∗Correspondingauthor.
E-mail:[email protected](J.Kattan). http://dx.doi.org/10.1016/j.jped.2016.10.004
withrespiratoryorcardiacfailure,andthattheywillbeavailableforanincreasingnumberof patientsfromthisregioninthenearfuture.
©2016SociedadeBrasileiradePediatria.PublishedbyElsevierEditoraLtda.Thisisanopen accessarticleundertheCCBY-NC-NDlicense(http://creativecommons.org/licenses/by-nc-nd/ 4.0/).
PALAVRAS-CHAVE Oxigenac¸ãopor membrana extracorpórea; ECMO;
Insuficiência respiratória; Insuficiência cardíaca; Hipertensão pulmonar; ELSO
Oxigenac¸ãopormembranaextracorpóreaneonatalepediátricaempaíses emergentesdaAméricaLatina
Resumo
Objetivo: Analisarosfundamentos,prognósticoeestabelecimentodaterapiadeoxigenac¸ão por membrana extracorpórea ECMO neonatal-pediátrica em países da América Latina com recursoslimitados.
Fontes: AbasededadosPubMedfoi exploradade1985atéhoje,selecionandoosprincipais periódicosdaAméricaLatinaerelatosdaOrganizac¸ãodeSuportedeVidaExtracorpóreo.
Resumodosachados: Aoxigenac¸ãopormembranaextracorpóreaproporciona‘‘tempo’’para descansopulmonarecardíacoepararecuperac¸ão.Elaéusadanocamponeonatal-pediátrico como terapia de resgate, com mais de 1.300 pacientes com insuficiência respiratória e cerca de 1.000 pacientes com cardiopatias por ano. Os melhores resultados de sobrevida de curto e longo prazo são de pacientes com doenc¸as respiratórias isoladas, estabele-cendo uma terapiapadrão em centros deencaminhamentopara pacientesde alto risco. O primeiroprogramadeoxigenac¸ãopormembranaextracorpóreaneonatal/pediátriconaAmérica Latina foiestabelecidonoChileem 2003,quetambémfoioprimeiro programanaAmérica Latina a se afiliar à Organizac¸ão de Suporte de Vida Extracorpóreo. Novos programas de oxigenac¸ão pormembrana extracorpórea foramdesenvolvidos nosúltimos anosem centros de encaminhamento naArgentina,Colômbia, Brasil, México,Peru, Costa Ricae Chile, que atualmente estãofundando asec¸ão daAmérica Latina daOrganizac¸ão deSuporte de Vida Extracorpóreo.
Conclusões: Osmelhoresresultadosdesobrevidadecurtoelongoprazosãodepacientescom doenc¸as respiratórias isoladas. Atualmente, a terapia de oxigenac¸ão por membrana extra-corpórea éuma terapia padrão em alguns centrosde encaminhamento daAmérica Latina. Esperamos queessesnovoscentrosdeoxigenac¸ãopormembranaextracorpórea tenhamum impacto positivosobreasobrevida deneonatos ecrianc¸as cominsuficiência respiratória ou cardíaca eque estejamdisponíveis para umnúmero cadavez maiordepacientesde nossa regiãonofuturopróximo.
©2016SociedadeBrasileiradePediatria.PublicadoporElsevierEditoraLtda.Este ´eumartigo Open Accesssobumalicenc¸aCCBY-NC-ND(http://creativecommons.org/licenses/by-nc-nd/ 4.0/).
Introduction
Extracorporealmembraneoxygenation(ECMO)or
extracor-poreallifesupport(ECLS)isatherapythatusesamodified
partial cardiopulmonary bypass to provide pulmonary
and/or cardiac supportfor an extended period,generally
one to four weeks (Fig. 1). It is used for patients with reversiblecardiopulmonary failuredueto pulmonary, car-diac,orotherdiseases.ECMOprovidestimeforapulmonary and/or cardiac rest and for recovery. Given that ECMOis invasive,itinvolvespotentialrisks,thuscriteriahavebeen establishedtoselectpatientswitha50---100%predictionof mortality.The idealECMOcandidatehasahighprediction ofmortality,butwithapotentiallyreversiblepulmonaryor cardiovasculardisease.1,2
The first adult survivor of ECMO therapy was treated in 1971 by J. Donald Hill, who used a Bramson oxygena-torwitha polytraumatizedpatient.1 However,bythelate
1970s the use of the therapy withadults was abandoned
becauseof poor results in controlled studies. Years later ECMOexperiencedaresurgenceforneonatalandpediatric patientsthanksthesurgeonRobertBartlett.1In1975atthe
Orange County Medical Center, Bartlett successfully used ECMOwith an abandoned Latin newborn suffering froma respiratorydistresssyndrome.1TheuseofECMOwith
new-bornsincreasedin thelate1980swithsurvivalof closeto 80%amongpatients with60---80% predictionsof mortality. OwingtotheincreaseduseofECMOwithneonatalpatients, avoluntaryalliance,theExtracorporealLifeSupport Orga-nization(ELSO),wasformedamongECMOcentersin1989.1
Newbornsare the principal age group for which ECMO therapyismuchsuperiortomaximumconventionaltherapy, asshowninacontrolledandrandomizedmulticenterstudy with185newborns withsevere respiratoryinsufficiencyin 55hospitals in theUnited Kingdom.3---5 This study showed
Venous saturation
monitor
Bladder Hemofilter
/shunt
Sample Pressure
monitor
Centrifugal
pump Heparin infusion
Oxygenator
Air bubble detector
Pressure monitor Transonic flowmeter Temp
monitor
Figure1 Schemeofvenoarterialextracorporealmembraneoxygenation(ECMO)circuitwithcentrifugalpumpand polymethylpen-teneoxygenator. Venousbloodisobtainedfromtherightatriumviatherightinternaljugularvein, thenpumped, oxygenated, heated,andreturnedtotheaortaviatherightcarotidartery.PublishedwithauthorizationfromtheECMOManualoftheChildren’s NationalMedicalCenter,GeorgeWashingtonUniversity,WashingtonD.C.,2010.
ECMOgroup).4---6At 7yearsfollow-up, 76%of thechildren
hadnormalcognitivedevelopment.5
SystematicreviewsshowthattheuseofECMOwith new-bornsclosetoterm withseverebut potentiallyreversible respiratory failure significantly improves survival without increasingseveredisability,whilebeingcost-effective com-paredtootherintensivecaretherapies.7,8
With respect to the use of ECMO as a rescue therapy for newborns withcongenital diaphragmatic hernia (CDH) withsevererespiratoryfailure,controlledprospective stud-iesindicatereductionsonlyinearlymortality.3,9However,a
meta-analysisofretrospectivestudiesandtheauthors’own experienceindicateahigherrateofshortandlong-termCDH survivalinhealthunitsthatincludeECMO.9---11
Newtherapiesemergedinthe1990stocombat cardio-respiratorypathologies,suchashigh-frequencyoscillatory ventilation (HFOV), surfactants, and inhaled nitric oxide (iNO).12WiththesetherapiesinassociationwithECMO
cen-ters, the morbimortality of these pathologies has been significantlyreducedinmoredevelopedcountries.5
AccordingtotheELSO,inthelastdecadeECMOhasbeen usedannuallyasarescuetherapyforcloseto800newborns whodid not respondto intensive care withHFOV and/or iNO.2,13 Currently, the rate of use of ECMO in the USA is
approximatelyonenewbornforevery5000livebirths.2This
therapy hasclearlyshown a higherrate ofglobal survival (74% to hospital discharge) among newborns with severe respiratoryinsufficiency, betterqualityof futurelife,and afavorablecost-effectivenessratio.2,6
The indications that lead to using ECMO for pediatric patientsaremorediverseanddifficulttodefinethanthose forneonatalpatients.14,15Nevertheless,inrecentyearsthe
number of respiratory cases reported to ELSO has risen to around 500 children per year, with a global survival
rate of 58% to hospital discharge or transfer.2,13,14 Acute
hypoxicrespiratoryfailure(HRF)isthemostcommon respi-ratoryconditionfor accepting patientsfor ECMO.16 Inthis
group,viralpneumoniaisthemostcommoncauseandone of the conditions with the best survival rates, together withaspirationpneumoniaandacutepost-traumatic respi-ratory distress.15 Nowadays, patients are accepted who
have immunosuppressionand suspicion of sepsis, the lat-teroftenwithmulti-organfailure.16Thegroupsofpediatric
patients with the poorest prognoses are those that have had bone marrow transplants or pneumonia associated with Bordetellapertussis and pulmonary hypertension, as well as patients with multi-organ failure, in contrast to the good prognosis for patients with isolated pulmonary involvement.16
Inthe1970sECMOwasusedtomanagerespiratoryfailure andpulmonary hypertension,andsomewhatlaterfor ven-tricularcardiacassistance.In1972,Dr.Bartlettsuccessfully providedECMOsupporttoa2yearoldboyfollowinga Mus-tardprocedureforcorrectionoftranspositionofthegreat vesselswithsubsequentcardiacfailure.1Halfofthepatients
who require cardiac ECMO have complex cyanotic con-genitalheart disease.2 The largest groups requiring ECMO
arepatients followingcardiotomyby acomplete AVcanal (20%)andpatientswithsingleventriclephysiology(17%)or tetralogyofFallot(14%).17Amongthemaincausesthatlead
toapplyingperi-operativecardiacECMOare:hypoxia(36%), cardiac arrest(24%), and failureto weanfrom cardiopul-monarybypass(14%).Consequently,theuseofiNOandHFOV canreducetheneedforECMObydecreasingthedegreeof hypoxia.17
0
n
1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017
2 4 6 8 10 12 14 16 18 20
Neo-ped-adult ECMO center start
Neo-ped ELSO affiliation
Adult ELSO affiliation
22 24 26 28 30 32 34 36 38
ECMO Centers in Latin America over time
Figure2 Numberofextracorporealmembraneoxygenation(ECMO)centerscreatedinLatinAmericasince1993(blacksquares), andthenumberofthisECMOcentersinLatinAmericaaffiliatedtotheExtracorporealLifeSupportOrganization(ELSO)andLATAM ELSOsince2003,separatedinneonatal-pediatriccentersandadultcenters(whitesquaresandtriangles,respectively).Asterisk(*) markstheyear2003,whenthefirstneonatal-pediatricECMOcenterstarted.
Neonatal-pediatric cardiac indications have been
increasingsteadilyovertime,reachingmorethan1000cases reportedtoELSOannually,constitutingavaluablesupport therapyinhigh-complexitycardiacsurgerycenters.2,18
Until2009,closeto80%ofthemorethan50,000patients treatedwithECMOandreportedtotheELSOwerenewborns orchildren,withnewbornstreatedforrespiratoryproblems representing approximatelyhalf ofall reportedpatients.2
In recent years, adult respiratory and cardiac ECMO has increasedprogressivelyby1500%,andpediatricrespiratory ECMOhasincreasedby100%,partiallyexplainedbythe pan-demic H1N1influenzaandnewevidencefromrandomized trialsinadults.19,20
Given the evidence of clear benefits in survival, qual-ity of life, and cost effectiveness of this therapy, and the absence of a formal ECMO program in Chile, it was decided in 1998 to establish a neonatal-pediatric ECMO programintheneonatalintensivecareunitattheCatholic University Hospital (ECMO-UC Program), in accordance with the standards of the ELSO for patients with severe but reversible cardiovascular or respiratory insufficiency refractory tomaximum conventional treatment.21,22 Work
began in 1999 on developing a multidisciplinary team (neonatologist, intensive care pediatricians, cardiac and pediatric surgeons,nurses,perfusionists, respiratory ther-apists,psychologists)withtraininginECMOcentersin the USA affiliatedto theELSO.21 Trainingwasconsolidated in
Chilewithanexperimentalcourseusingsheep.21
In2003,thefirstneonatal-pediatricECMOprogramwas consolidatedin Chileandbecame thefirstLatinAmerican memberoftheELSO(Fig.2).FromMay2003toJune2016, thecentertreated181patients(155newbornsand26 chil-dren),withbothsevererespiratoryandcardiacpathologies. To determine the impact of the establishment of a neonatalECMOprogramontheoutcomeofnewbornswith severeHRFinadevelopingcountrylikeChile, theauthors studieddataofnewborns (BW>2000gandGA≥35weeks)
withHRF and oxygenation index(OI) >25 were compared beforeandafterECMOwasavailable.11ECMOwasinitiated
in infants with refractory HRF who failed to respond to iNO/HFOV.Datafrom259infantswereanalyzed;100born
in the pre-ECMO period and 159 born after the ECMO program was established. Survival significantly increased from 72% before ECMO to 89% during the ECMO period. Duringthe ECMO period, 98/159 (62%) patients withHRF were rescued using iNO/HFOV, while 61 (38%) did not improve;52ofthese61neonateswereplacedonECMO.11
The ECMO survival rate to hospital discharge was 85%. Afteradjusting for potential confounders,the severity of the pretreatment OI, late arrival to the referral center, the presence of a pneumothorax, and the diagnosis of a diaphragmaticherniaweresignificantlyassociatedwiththe needfor ECMOordeath. The conclusionofthisstudy was thattheestablishmentofanECMOprogramwasassociated withasignificant increaseinthesurvivalofnewborns≥35
weekswithsevereHRFinadevelopingcountry.11
In2013,inan editorialintheJournalofPediatric Crit-icalCareMedicine, Steinhorn andKeller commented that theChileanexperienceisnotableforanumberofreasons.23
‘‘Chileisaresource-limitedcountry,andECMOisnotoriously expensiveand resourceintensive becauseofthe need for sophisticatedequipmentandwell-trainednursesand tech-niciansforconstantmonitoring’’.23Theycontinuepointing
out:‘‘After beginning theECMO program, nearly oneout ofevery10,000neonatesborninChilewastransferredtoP. UniversidadCatólicadeChileforadvancedrespiratorycare. Establishing the program and facilitating complex trans-portsof criticallyillinfantsacross alargecountryis truly a remarkable achievement. In an era when the expendi-tureofeconomicresourcesonpediatrichealthcareisbeing scrutinized,itisencouragingtoseeChile’scommitmentto enhancingthesurvivalofinfantsintheircommunity, know-ingthatgoodqualitysurvivalofinfantswithECMOislikely to return more over the years than the initial expendi-tureof resources’’.23 Steinhorn and Kellerconcludedthat
160
140
120
100
80
60
40
20
0 Argentina
Number of ECMO cases
Neonatal ECMO Pediatric ECMO
Number of ECMO cases in neonates and children by Latin American country (2003-2014)
71 83
16 23
140 66
4 37
1 2 Brazil Chile Colombia Mexico
Figure3 NumberofECMOcasesinneonatesandchildrenby LatinAmericancountryinmainextracorporealmembrane oxy-genation(ECMO)centersbetween2003and2014.Dataobtained byLATAMExtracorporealLifeSupportOrganization(ELSO) Sur-vey2014,presentedatthe25thELSOMeetinginAnn Harbor, Michigan,2014.
InBucaramanga,Colombia,areportfromtheFundación
CardiovasculardeColombiain2013showedthatinspiteof
reducedavailabilityof technicaland economic resources, ECMOtherapycanbeimplementedsuccessfullyina develop-ingcountry.TheirmodelofcareisbasedonnursesasECMO specialistssupportedbyamultidisciplinaryteam.Their pro-tocolwithreducedcircuitryandlaboratorymonitoring,and asimpleandlessexpensivecircuitareimportantfor good
outcomes with reduced staff.24 Recently, Miana LA from
theHeartInstitute,UniversityofSaoPaulo,Brazil, demon-strated that investment in ECMO team training combined with a cost-effective investment in technology can bring significantbenefitsinpostcardiotomypatients.25
Following the Euro-ELSO and Asia-Pacific ELSO exam-ples, in 2012 Latin America created the local chapter of ELSO(LATAMELSO),withthemissionofcontributingtothe disseminationofECMOtherapyaccordingtothe recommen-dations of the ELSO, practical and theoretical education throughcourses andworkshops, and encouraging collabo-rativeworkamongLatinAmericancenters.TheLATAMELSO foundationwas basedin Santiago, Chile, duringthe Latin AmericanECMOSymposium2012.About 250 ECMO practi-tionersfromLatinAmericaattendedtheevent,whichalso featuredtheparticipationofELSOrepresentatives(Dr.Steve Conrad, Dr. Michael Hines, Peter Rycus, and Dr. William Lynch).
In the last decade, new neonatal-pediatric ECMO pro-grams have been established in high-complexity and high-volume centers in several Latin American countries, suchasArgentina,Colombia,Brazil,Mexico,Perú,andCosta Rica.21,26---28Themajorityofthesecentershaveprogressively
entered the ELSOand the LATAM ELSOchapter. Afterthe LATAM ELSO chapter was created, a notable increase of ECMOcenterswereseen in the region(Fig.2).There are currently33 ELSO centersin seven countries,16 of them neonataland/orpediatriccenters,withmorethan270 new-bornsand 220 children reported toELSO upto July 2016 (Fig.2).2 As seen inFig.3,the proportionof neonatalor
pediatricECMOpatientsdiffersineachcountry,withmore neonatalcases in Chilecompared to pediatric cases, but
more pediatric cases in Colombia, Argentina, and Brazil, comparedtoneonatalcases(Fig.3).
As Caneo from Sao Paulo, Brazil recently commented: ‘‘The goodnews is thatwiththe supportof expertsfrom theUSA,Europe,andCanada,theresultsinLatinAmerica’s ELSOcentersareimproving by followingitsguidelinesfor training,andusingastandardeducationalprocess’’.29
ECMO
physiology
During extracorporeal support the blood is drained from
the patient to an external pump (roller or centrifuge),
whichpumpsthebloodthroughanexchangemembrane
(sil-iconorpolymethylpenteneoxygenator)foroxygenationand CO2 removal,and aheaterfor returningthe blood tothe
patient’scirculation (Fig.1).Thistherapyrequires antico-agulationofthecircuitanduseofheparinadministeredto the ECMOcircuit, withtheaim of avoidingactivating the coagulationcascade.Aswell,severalpressure,flow,bubble, and temperature monitors are used. Continuous coagula-tionmonitoring is essential,withhourly measurementsof activatedclottingtime(ACT),anti-factorXalevel,platelet count,fibrinogenlevels,andinsomepatients,anti-thrombin IIIlevelandthromboelastography.30
ThereareessentiallytwoformsofECMO:
(a) Veno-arterial(VA):inwhichtheblood isdrainedfrom the right atrium with a cannula inserted in the right internal jugularvein, femoral vein,or directly in the right atrium, and is returned to the thoracic aorta through a right, femoral, or aortic carotid cannula (Fig.1).VA-ECMOprovidescardiacandpulmonary sup-port.Transthoraciccannulas(rightauricularandaortic cannula) are often used with postoperative cardiac patients.30
(b) Veno-venous(VV):inwhichthebloodisdrainedfrom
the right atriumthrough the posterior and lower ori-fices of a double-lumen cannula inserted in the right jugularandreturnedtothesameright atriumthrough the anterior orifices of the same cannula, which is directedtowardthetricuspidvalve.Oneofthelimitsof thismethodistherecirculationofalreadyoxygenated blood through the double-lumen cannula, which has beencorrectedwithnewVVcannuladesigns.VV-ECMO is also performed on older children with the use of two cannulas, removing blood from the jugular vein and returning it through the femoral vein. VV-ECMO requires awell-functioningheart. ThisECMOmodality avoidscannulationofthecarotidorfemoralartery,thus decreasing complications arising from cannulation or fromligationofthesearteriesandfromtheentryofair intheECMOcircuit.Theuseofthismodehasincreased inrecentyears;itisnowusedinaround40and50%of neonatalandpediatricrespiratorycases,respectively.30
WithbothformsofECMO,theventilatorandFiO2
param-eters arekept low toallow for the lungs torecover, but generally positive end-expiratory pressure(PEEP) remains high(6---8cmH2O)toavoidatelectasis.
through the extracorporeal circuit, oxygenation through the native lung, and native heart output.30 In turn,
oxy-genation in the ECMO membrane is a function of the membrane’sgeometry,materialcompositionandthickness, blood and FiO2 laminar thicknesses, the time red cells
remain in the exchange area, hemoglobin concentration, andO2saturation.30
CO2removalbyECMOisafunctionofthegeometry,
mate-rialandsurfaceareaofthemembrane,bloodpCO2andtoa
lesserdegreebloodandgasflowsthroughthemembrane.30
The bypass in VA-ECMO generates an essentially non-pulsatile blood flow. As the flow of blood to the extracorporealcircuitincreases,thepulsewavedecreases, andwith100%bypassceasescompletely, exceptfor occa-sionalwaves. However,normallyVA-ECMOinvolves an80% bypass, leaving 20% or more of blood circulated by the heart and lungs, resulting in a highly reduced but visi-ble pulse.30 The kidney is undoubtedly themost affected
organ by the absence of pulsatility, resulting in an anti-diuretic effect owing to juxtaglomerular stimulation. As well,non-pulsatileflow hasbeen relatedtostimulationof the pressure receptors of the carotid sinus, provoking a majorreleaseofcatecholamine,withdeleteriouseffectson microcirculation.30
Selection
criteria
for
applying
ECMO
The criteriadiffer for neonatal or pediatric patients and dependonwhetherthecauseisprimarilycardiacor respi-ratory.Thecriteriaaregeneralandshouldbeindividualized foreachpatient,evaluatingtherisksandbenefitsof apply-ingECMO.16
• Gestationalage≥34weeks • Weightatbirth≥2kg
• Unresponsivetomaximummedicaltreatment(HFOV,iNO,
surfactant)
• Reversiblecardiopulmonarycondition • Mechanicalventilation≤10---14days
• Highpulmonarymortality(50---100%).Oneofthe
follow-ing:
- OI>40for4h(iNO,HFOV)
- PaO2<40---50mmHgfor4h(100%O2)
- GradientA/aDO2>600mmHgfor4h
- OI≥25after72hwithHFOV-iNO31
• Unmanageablemetabolicacidosis(pH<7.15for2h) • Reducedcardiacoutputwithreversibleetiology • Impossibilitytoweanfromcardiopulmonarybypass • Asabridgeforcardiactransplant32
• Withoutpost-cardiacsurgerylesions • Absenceofmajorintracranialhemorrhage • Absenceofuncontrollablehemorrhage • Withoutevidenceofmassivecerebraldamage
• Withoutmalformationsorsyndromeswithfatalprognosis
The fundamental criteria are similar for pediatric patientswithrespiratoryfailure,withparticularemphasis onwhetherthepatientfacesaseriouspulmonaryriskwith highriskofdeath,butpossiblereversibilityofthecondition through respiratory, gasometrical, and hemodynamic repose.Amongthepediatriccriteriaare14:
• OI >40 for 6h in invasive mechanical ventilation (IMV)
and/orHFOV
• OI>35for>12h
• Adverseeffectsofmechanicalventilation • Mechanicalventilation≤10---14days • HypercapniawithpH<7.1for4h
• Acutedeteriorationwithoptimaltherapy
SpecificcontraindicationsforECMOforcardiacpatients arethepresenceofresidualpost-surgicallesionsand con-traindications for cardiac transplant.However, each case shouldbeanalyzedindividuallygiventhatthe contraindica-tionscanberelativeorcanchangeovertime.17,33Amongthe
cardiacor hemodynamic indicationsfor pediatric patients are:
• Severe but potentially reversible cardiovascular failure
that does not respond tovasoactive, vasodilatation, or anti-arrhythmicdrugs
• PersistentSVO2<60%;pH<7.15
• Failure to wean from cardiopulmonary bypass after
surgery
• Severearrhythmiawithpoorperfusion
• Rapidventriculardeteriorationorseveredysfunction
Managing
ECMO
Theinitialparameterspointtoachievingabypassof50%or
moreofcardiacoutput(estimatedat 200mL/kg/min)and
areadjusted to maintain adequate pressure and an
acid-basestate.Whencardiacfunctionisconservedandthemain pathologyispulmonary,VV-ECMOcanbeusedtoassist oxy-genationandventilation.Meticulousattentiontoallaspects of the patient is essential. Frequent checks are required ofblood gases,theECMOcircuit,clotting, andrenal func-tion,as well ascerebral ultrasound assessment in search ofintracranialhemorrhageandcerebralinfarction.Patients aresedated,butgenerallynotparalyzed,whichfacilitates
neurological assessment. To the degree that the patient
improves,ECMOsupportisgraduallyreduced.Patientsare
decannulatedwhenthey cannottolerate aminimal ECMO
support(10%ofbypassesinVA-ECMO)withlow-to-moderate
mechanicalventilationparameters.ECMOtreatment
gener-allylasts between fiveandtendaysfor neonatalpatients withrespiratorydiseases,andlongerincasesofCDH(10---12 daysonaverage).2
Complications
TheECMOprocedurehasseveralrisksofcomplicationsfrom
the use of anticoagulants and changes in blood flows as
a consequence of the seriousness of the patient’s
condi-tion upon entering the ECMO. Among the most common
complicationsarehemorrhage(surgicalsite6%,pulmonary 4%,gastrointestinal2%),infarctionorcerebralhemorrhage (9% and 5% respectively), convulsions (11%), cardiac
dys-function (myocardial stunning 6%, arrhythmia 4%), kidney
failure(4%), sepsis (6%), hyperbilirubinemia(9%), arterial hypertension(12%),andhemolysis (13%).2By farthemost
94 84 77 72 58 51 94 100 56 40 54 82 63 61 0 20 40 60 80 100 120
MAS HMD PPHN Sepsis Others PN CDH
ELSO LATAM
ECMO survival to hospital discharge in newborns with respiratory diseases
ELSO 1985 - 2016 n=29 153 ELSO LATAM 2003 - 2016 n=219
%
n=7.765
n =8.994
n =36
n=137
Figure 4 Survival to hospital discharge of 29,153 and 219 newbornstreatedwithextracorporealmembraneoxygenation (ECMO), reported to the international Extracorporeal Life Support Organization (ELSO) and LATAM ELSO, respectively, accordingtotherespiratorycause.MAS,meconiumaspiration syndrome;HMD,hyalinemembranedisease;PPHN,persistent pulmonaryhypertensionofthenewborn;PTX,pneumothorax; PN,pneumonia;CDH,congenitaldiaphragmatichernia.
forvasoactivedrugsduringextracorporealsupport,followed bysurgicalsitebleeding.34
Intracranial hemorrhage is the primary cause of death duringECMO,andtheappearanceofconvulsions issignof apoorprognosis.Additionally,therearecomplications aris-ingfromcircuitfailuresoftheoxygenatororofotherECMO equipment.2
ECMO
prognosis
and
follow
up
Post-ECMOsurvivalamongneonatalpatientsvaries accord-ingtothe underlying disease,with caseswithrespiratory
ECMO survival to hospital discharge in 181 patients (155 newborns and 26 children) from the ECMO-UC program by
principal diagnosis. Years 2003 –2016
92 83
67 70 73
60 72 0 10 20 30 40 50 60 70 80 90 100 MAS Neonatal pneumonia /sep sis
PPHN CD H Pedi atric resp irato ry Neo natal /Ped card
iac Total
%
n=95
n=26
Figure 5 Survival to hospital discharge of 155 neonatal and 26 pediatric patients treated in the Neonatal-Pediatric extracorporealmembraneoxygenation(ECMO)Programatthe CatholicUniversity HospitalinSantiago,Chile(ECMO-UC Pro-gram)2003---2016,reportedtotheExtracorporealLifeSupport Organization(ELSO)accordingtothemaindiagnosis.
causeshavingthebestresults,demonstratingcloseto70% survivaltohospitaldischarge,accordingtoELSOandLATAM ELSO reports2 (Figs. 4 and 5). Among all the respiratory
causes,neonateswithmeconiumaspirationsyndrome(MAS) havethehighestsurvivalrate:94%tohospitaldischarge2,3
(Figs.4and5).VVECMOisgenerallyusedforSAM,whichis associatedwithalowerrateofrisksandcomplicationssuch ascerebralinfarctionsandconvulsions,andminorchanges inbloodflowpatterns.
Conversely, patients treated with ECMO for cardiac causeshavealowersurvivalrate,closeto45%.2,13,33
Never-theless,forwell-selectedpatientsECMOisausefultoolthat shouldbeavailableinhighlycomplexcardiologycenters.17
Among thepatients treatedwithECMOfor cardiac causes are notably those with cardiomyopathy and myocarditis, with survival rates to hospital discharge of 61 and 51%, respectively.2,13,33 In recent years ECMO has been used
asapost-cardiopulmonary resuscitationtoolwithvariable results,withsurvivalratesofcloseto40%.2,13
The survival and neurological prognosis at five years amongpatientstreatedwithECMOfornon-cardiaccausesis ingeneralverygood,butworsenswithalowergestational age,alowerbirthweight,andahigherpre-ECMOOI.35The
poorestsurvivalandneurologicalevolutionresultsarewith patientswithdiagnosesofsepticshockandCDH. Neverthe-less,pre-existingfactorsandtheseverityof thenewborns upon enteringECMOappeartobethemajordeterminants ofthelong-termprognosis.10,35,36
Thelong-termrespiratoryprognosisdependsonthebase etiology, the degree of barotrauma, and the duration of exposuretooxygen.Between 10and30% ofpatientswith CDH have episodes of wheezing by the age of 10 and closeto50%havehyperinsufflationandepisodesofairway obstruction.37,38
ECMO survival to hospital discharge in pediatric patients
with respiratory diseases
ELSO 1985 - 2016 n=7552
ELSO LATAM 2003 - 2016 n=76
69 66 62 60 56 53 52 71 70 63 40 56 54 0 10 20 30 40 50 60 70 80 Aspi ratio
n pn eum onia Vira l pn eum onia ARD S pos
top/ traum a Bac terial pneu moni a ARDS not p
osto p/tra
uma
Acut e res
pirat ory failu re Pneu mocy stis pneu mon ia Othe r
ELSO survival LATAM survival
% n = 1637 n=2 8
Post-ECMOsurvivalis lowerforpediatric thanneonatal patients,althoughthereisabetterprognosisinthegroup withrespiratoryfailure,especiallypatientswithaspiration
pneumonia, viralpneumonia, andacute post-operativeor
post-traumatic respiratory distress syndrome (Fig. 6).15,39
Viralpneumonia isthe mostcommoncondition leadingto pediatric ECMO; among its etiologies, respiratory syncy-tialvirushasthehighestpost-ECMOsurvivalrateat70%.15
Patientswithpneumoniacausedbyothervirusesandby Bor-detellapertussishavelowersurvivalratesof56%and39%, respectively.15,39
The pediatric patients who receive ECMO due to car-diac causes have a somewhat higher survival rate than their neonatal counterparts2,13 (55% survival to hospital
discharge), highlighting the survival rates to hospital dis-chargeof72%and61%formyocarditisandcardiomyopathy, respectively.2,13
After13years,fromMay2003toJuly2016,theECMO-UC centertreated181patients(155newbornsand26children, rangingfrom0to11yearsofage),withbothsevere respira-toryandcardiacpathologies(Fig.6).72%ofthesenewborns andchildrensurvivedtohospitaldischarge.The51patients thatdiedhadasbasediseases:CDH(n=29),congenitalheart diseaseoperatedwithfailuretoweanfromcardiopulmonary bypassorarrhythmias(n=11),persistentpulmonary hyper-tensionsecondarytosepsis,pneumonia,MAS,SP-BorABCA3 deficiency,orwithoutdefinedcause(n=10),andpneumonia duetoBordetellapertussis(n=1).2Amongpatientstreated
withECMO,therearenotablynewborns withCDH, witha survivalrateof70%tohospitaldischarge(66/95).2
All the survivors in the ECMO-UCprogram in Chileare currentlyinaspecialECMOfollow-upprogram.38Amongthe
neurologicalfollow-upexams,theBayleyII testsat12---18 monthsshowed that over 90% ofthe children had normal or slightly altered mental development indices (MDI) and morethan70%hadnormalorslightlyalteredpsychomotor developmentindices(PDI).38Aswell,nopatientpresented
disablingvisualorauditoryalterations.IntheCDHpatient follow-up,over80%hadanormalMDIfromtheBayleyIItests at12---18months,andsimilartotheentiregroup,over70% hadanormalorslightlyalteredPDI.
Withrespecttorespiratoryfollow-up,83%ofthepatients hadanormalorslightlyalteredclinicalbronchopulmonary, and27%hadmoderatebronchialhyperreactivityinthe eval-uationat3yearsofage.38
TheestablishmentofanECMOprograminChilewas asso-ciatedwithasignificantincreaseinthesurvivalofnear-term newbornswithsevererespiratoryinsufficiency.ECMO ther-apywassuccessfulanddidnotprovokedisablingsequelae inthemajorityofthepatients.
Conclusions
and
future
considerations
ECMO therapy, now termed more broadly as ECLS, is
a standard therapy in neonatology and pediatrics, with
demonstrated short- and long-term benefits. It can be
incorporated into intensive therapy with good results in
developingcountries,butrequireshighlycomplexneonatal andpediatriccenterswithtrainedandcommittedstaff.
FuturepatientswhoaretreatedwithECLSwillbe
pro-gressively more complicated, therefore new and simpler
automatedECLSmodalitieswillberequired,withlessneed foranticoagulants,withtheaimof minimizingthe
associ-ated risks and making their extended use possible. Thus
newbornsandchildren withsevere conditionscanbe
sub-mittedtoECLSforheartandlungtransplant,orasbridgeto ventricularassistancedevices.18,32,33 Evenpremature
new-bornswithseverecardiopulmonaryfailurecaninthefuture benefitfromumbilicalECLS,orlowbypassusinglungassist devices(LAD).40Newlow-resistancemicroporeoxygenators
canmakepumpsunnecessary,usingtheumbilicalarteryor veinasanarteriovenousshunt.41,42Moreover,newbornswith
CDHcanbeadmittedforearlyECLStreatmenttominimize pulmonarydamage andtofavorlung growthusinggrowth factorsand/orliquidventilationwithperfluorocarbon asso-ciatedwithECLS.Somecenters,liketheBostonChildren’s Hospital,havebeen usingex-uterointrapartum treatment (EXITtoECMO)forpatientswithCDHandprenatalmarkers ofpoorprognosis,ortoensureeffectiveventilationfor new-bornswhodonothavesafeairwaysorwhoareexpectedto experiencesevererespiratoryfailureuponbirth(CDH, cervi-calteratoma,airwaypathologies,largepulmonarymasses, bronchialcysts,etc.).43
TheauthorsexpectthatECLSwillallowthemtocontinue assistingpulmonaryandcardiacfunctioningmorerationally throughtherepairofseverebutreversiblecardiopulmonary processes.
ItishopedthatthenewECMOprogramsinLatinAmerica, asbenchmarkcenters, willhave apositive impactonthe survivalofnewbornsandchildrenwithrespiratoryorcardiac insufficiency,andthatthistreatmentwillbeavailabletoa greaternumberofpatientsinthisregioninthenearfuture.
Conflicts
of
interest
Theauthorsdeclarenoconflictsofinterest.
Acknowledgements
Theauthorswouldliketoacknowledgethefollowing
insti-tutions for their contributions to this ECMO program:
Extracorporeal Life Support Organization (ELSO); Latin
AmericanELSOChapter (LATAMELSO), Children’s National
Medical Center, George Washington University,
Washing-tonD.C.;W. H.TooleyNICU, University ofCalifornia,San Francisco;ChildHealthFoundation,UniversityofAlabama, Birmingham;EglestonChildren’sHospital,EmoryUniversity, Atlanta;Washington University,St.Louis;Ministry of Pub-licHealthofChile,andtheNeonatalDivision,Department ofPediatricsandtheDepartmentofCardiovascularDiseases andAnesthesia,PontificiaUniversidadCatólicadeChile.
The authors are very grateful tomany Latin American
ECMO Centers who contributed their ECMO patient data:
Argentina:HospitalProf.Dr.JuanPedroGarrahan,Buenos
Aires;HospitalUniversidadAustral,Pilar,BuenosAires; Hos-pitalSorMaría Ludovica, LaPlata, Buenos Aires;Hospital Italiano, Buenos Aires; Clínica Bazterrica, Buenos Aires;
Hospital Universitario Fundación Favaloro, Buenos Aires.
Brazil: HeartInstituteInCor,SaoPaulo; Hospitalde
Clíni-cas,UniversidaddeSaoPaulo,Campinas,SaoPaulo;Hospital
da Bahia, Salvador da Bahia. Chile: Clínica Las Condes,
Santiago; Hospital Roberto del Rio, Santiago. Colombia:
FundaciónCardiovasculardeColombia,Bucaramanga;
Fun-daciónClínica Shaio,Bogotá; Clínica CardioVID, Medellín.
Mexico:HospitalChristusMuguerza,Monterrey.Paraguay:
HospitalPediátricoNi˜nosdeAcosta ˜Nu,SanLorenzo.Peru: andHospitalNacionalEdgardoRebagliatiMartins,Lima.
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