Epidemiology of pediatric cardiopulmonary resuscitation 夽,夽夽

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JPediatr(RioJ).2020;96(4):409---421

www.jped.com.br

REVIEW ARTICLE

Epidemiology of pediatric cardiopulmonary resuscitation ^夽,夽夽

Tania Miyuki Shimoda-Sakano

^a^,^b^,^c^,^d^,∗

, Cláudio Schvartsman

^a^,^b

, Amélia Gorete

Reis

^{a,b,e a}^,^b ^,^e

aUniversidadedeSãoPaulo(USP),Pediatria,SãoPaulo,SP,Brazil

bUniversidadedeSãoPaulo(USP),FaculdadedeMedicina,HospitaldasClínicas,ProntoSocorrodoInstitutodaCrianc¸a,São Paulo,SP,Brazil

cSociedadedePediatriadeSãoPaulo(SPSP),DepartamentodeEmergência,Coordenac¸ãoRessuscitac¸ãoPediátrica,SãoPaulo,SP, Brazil

dSociedadedeCardiologiadeSãoPaulo,CursodePALS(PediatricAdvancedLifeSupport),SãoPaulo,SP,Brazil

eInternationalLiaisonCommitteeonResuscitation(ILCOR),Brazil

Received1July2019;accepted31July2019 Availableonline30September2019

KEYWORDS Cardiopulmonary resuscitation;

Cardiopulmonary arrest;

Ventricular ﬁbrillation;

Pulselessventricular tachycardia;

Asystole;

Pulselesselectrical activity

Abstract

Objective: Toanalyzethemainepidemiologicalaspectsofprehospitalandhospitalpediatric cardiopulmonaryresuscitationandtheimpactofscientiﬁcevidenceonsurvival.

Sourceofdata: This wasanarrativereview oftheliteraturepublishedatPubMed/MEDLINE untilJanuary2019includingoriginalandreviewarticles,systematicreviews,meta-analyses, annalsofcongresses,andmanualsearchofselectedarticles.

Synthesisofdata: Theprehospitalandhospitalsettingshavedifferentcharacteristicsandprog- noses.Pediatricprehospitalcardiopulmonaryarresthasathree-foldlowersurvivalratethan cardiopulmonaryarrestinthehospitalsetting,occurringmostlyathomeandinchildrenunder 1year.Highersurvivalappearstobeassociatedwithageprogression,shockablerhythm,emergency medicalcare, use ofautomaticexternaldeﬁbrillator, high-qualityearlylife support, telephone dispatcher-assistedcardiopulmonaryresuscitation,andisstronglyassociatedwith witnessedcardiopulmonaryarrest.Inthehospitalsetting,ahigherincidencewasobservedin childrenunder1yearofage,andmortalityincreasedwithage.Highersurvivalwasobserved withshortercardiopulmonaryresuscitationduration,occurrenceonweekdaysandduringday- time,initialshockablerhythm,andpreviousmonitoring.Despitethepoorprognosisofpediatric cardiopulmonaryresuscitation,anincreaseinsurvivalhasbeenobservedinrecentyears,with goodneurologicalprognosisinthehospitalsetting.

夽 Pleasecitethisarticleas:Shimoda-SakanoTM,SchvartsmanC,ReisAG.Epidemiologyofpediatriccardiopulmonaryresuscitation.J Pediatr(RioJ).2020;96:409---21.

夽夽StudyconductedatUniversidadedeSãoPaulo(USP),FaculdadedeMedicina,HospitaldasClínicas,InstitutodaCrianc¸a,SãoPaulo,SP, Brazil.

∗Correspondingauthor.

E-mail:sakano@hotmail.com(T.M.Shimoda-Sakano).

https://doi.org/10.1016/j.jped.2019.08.004

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Conclusions: Agreatprogressinthescienceofpediatriccardiopulmonaryresuscitationhasbeen observed,especiallyindevelopedcountries.The recognitionoftheepidemiologicalaspects thatinﬂuencecardiopulmonaryresuscitationsurvivalmaydirecteffortstowardsmoreeffective actions;thus,studiesinemergingandlessfavoredcountriesremainsapriorityregardingthe knowledgeoflocalfactors.

4.0/).

PALAVRAS-CHAVE Ressuscitac¸ão cardiopulmonar;

Parada

cardiorrespiratória;

Fibrilac¸ão ventricular;

Taquicardia ventricularsem pulso;

Assistolia;

Atividadeelétrica sempulso

Epidemiologiadaressuscitac¸ãocardiopulmonarpediátrica

Resumo

Objetivo: Analisar os principais aspectos epidemiológicos da ressuscitac¸ão cardiopulmonar pediátricapré-hospitalarehospitalareoimpactodasevidênciascientíﬁcasnasobrevida.

Fontededados: RevisãonarrativadaliteraturapublicadaPubmed/Medlineatéjaneirode2019, inclusiveartigosoriginaisederevisão,revisõessistemáticas,metanálises,anaisdeCongresso, alémdebuscamanualdosartigosselecionados.

Síntesedosdados: Os cenários pré-hospitalar e hospitalar apresentam características e prognósticosdistintos.Aparadacardiorrespiratóriapré-hospitalarpediátricaapresentasobre- vidatrêsvezesmenordoqueahospitalar,ocorreemsuamaiorianasresidênciasenosmenores deumano.Amaiorsobrevidapareceestarassociadaaprogressãodaidade,ritmochocável, atendimento por serviço médico de emergência, uso de desfibrilador externo automático, suporte básicode vidaprecoce de alta qualidade eorientação de ressuscitação cardiopul- monarviatelefônicaporatendenteeestáfortementeassociadacomparadacardiorrespiratória presenciada.No cenáriohospitalar, observou-se maiorincidênciaem menores deum ano e mortalidadecrescentecomaidade.Maiorsobrevidafoiobservadaquantomenorduraçãoda ressuscitaçãocardiopulmonar,ocorrênciaemdiasdasemanaeperíododiurno,ritmochocável inicial emonitorização prévia.Apesar doprognóstico reservadodaressuscitaçãocardiopul- monarpediátrica,observou-senosúltimosanosincrementodasobrevidacombomprognóstico neurológiconocenáriohospitalar.

Conclusões: Houve grande avanço na ciência da ressuscitação cardiopulmonar pediátrica, especialmenteempaísesdesenvolvidos.Oreconhecimentodosaspectosepidemiológicosque influenciamasobrevidadaressuscitaçãocardiopulmonarpodedirecionaresforçosparaações mais efetivas.Assim,a pesquisaem paísesemergentes emenos favorecidos persiste como prioridadenoconhecimentodefatoreslocais.

0/).

Introduction

Cardiopulmonaryresuscitation(CPR)asitiscurrentlyknown (chest compressions and artiﬁcial ventilation) was devel- opedin1960;sincethen,medicalentitieshavebeenworking ontheprogressofresuscitationscienceandinprogramsto disseminatethisprocedure,includingthetrainingofhealth- careprofessionalsandlaypeople.Despitemajoradvances, pediatriccardiopulmonaryarrest(CPA)stillhasapoorprog- nosis. Although in recent years there has been a trend towards increased survival of in-hospital pediatric CPA in developedcountries,thishasnotbeenobservedinprehos- pitalCPA,wherethemorbidityandmortalityratesremains high.^1,2

Factors associated withCPA survival remain a topicof great interest in the literature, which mainly addresses adultsindevelopedcountries.²Theepidemiologicalaspects associatedwithpediatricCPAarelessclearanddifferfrom thoseinadultsregardingetiologyandprognosis.^3,4

The main CPR topics that must be studied were high- lightedinarecentpublicationbytheInternationalLiaison Committee on Resuscitation (ILCOR), an entity that dis- cusses the science of CPR and brings together specialists fromseveral countries.⁵ This documentstressed theneed for studies focusing onthe epidemiology of pediatric CPA todetect variables thatcan influencesurvival andneurological prognosis.The Utstein style,developed in1990 by ILCOR, aimstostandardize terms anddefinitions for data collectionduringCPAandCPR,⁶ andhassincebecomethe international standard for researchdata collectionin this field.

In2004,theUtsteinstylewasrevised,aimingtodecrease its complexity, adapt the variables to the science of resuscitation,⁷ and unify the hospital registry of CPA in adults andchildren. Sincethen, there hasbeen a signiﬁ- cant increase in resuscitation registries and clinical trials in several regions, notably in the United States, Europe, Asia, Australia, and Japan.⁸ Increasing data have allowed

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Epidemiologyofpediatriccardiopulmonaryresuscitation 411 Table1 CharacteristicsofprehospitalCPAaccordingtoagerange.

Overall Infants Children Adolescents Adults

Incidence(100,000cases/year) 3.3-8.0 65.5---72 3.7 6.3 50---64.7

30-daysurvival(%) 8.1 1.4---2.6 7.8---16.1 7.7---9.3 9.3

Survival-hospitaldischarge(%) 1.1-20 3.3 9.1 8.9 1.1---10.6

Favorableneurologicalprognosis^a(%) 1-12 1-2 4 11---16 2---10.7

Publicplace(%) 7-12 4 14 22---45 16

CPRinthecommunity(%) 6---48.8 37 40 28 19

Initialrhythmasystole(%) 82---95 84 83 77 60

InitialrhythmVF(%) 5---11.7 4 5---22 15---51.2 23---33.7

a Studiesevaluated1to18monthsafterCPA.2,10,11,15,19,21

the comparisonof theepidemiology in differentregions,² CPAtherapeutics,andoutcomes,⁹inadditiontoidentifying knowledgegapsandadvancingthescienceofresuscitation.⁵ Therefore,thisstudyaimedtoreviewtheepidemiology of pediatric CPR, highlighting the possible factors associated with CPA prognosis and survival trends. Due to the heterogeneityofthestudies,theauthorschosetoperform anarrativereviewtointerprettheliterature.Thepost-CPR periodwasexcluded fromthis review, duetoits peculiar characteristics.

As the epidemiology of pediatric prehospital and in- hospitalCPAisdistinct,thisreviewwillpresentthefactors associatedwiththesetwodifferentscenarios.

Prehospital cardiopulmonary arrest

PrehospitalCPAisrareinchildrenandadolescents,occurring in2.28to8.04/100,000,incontrasttoadults,occurringin50 to126.57/100,000,andisassociatedwithhighmortalityand severeneurologicalsequelae.^10---12PediatricCPAaccountsfor only1.5to2.2%oftotalCPAs,accordingtorecentAsian¹³ andAmerican¹⁴ registrypublications,respectively.

The survival in CPA in the prehospital and in-hospital settings is distinct and varies according to region and country.^2,15---17 AEuropean registry inadults observed that 66%received CPRprior toprehospitalcare and10.3% had survival athospital discharge,¹⁸ similartothat found in a multicenterNorth-Americanstudythatincludedadultsand children.¹⁵

A systematic review includingadults and children disclosed a wide variation in the incidence and outcome of CPA across the continents, with the highest incidence in North America (54.6/100,000) and the lowest in Asia (28.3/100,000). The lowest survival rate at hospital discharge wasreported in Asia (2%), compared with Europe (9%),NorthAmerica (6%),andAustralia(11%).² Thisresult canbeattributedtothediversityamongpopulationswith distinct comorbidities, emergency medical service (EMS), deﬁnitions,studymethodologies,localtelecommunications system,incidenceofVFastheinitialrhythm,andregistry differences.

The neurological prognosisin pediatricprehospital CPA is very guarded. An American pediatric study showed an overallsurvivalatdischargeof8.6%,with31%showinggood neurologicalprognosis.¹⁹InJapan,theoverallsurvivalafter one month was8%,and goodneurological prognosis after

onemonth wasobserved in1% of infants, 2%of children, and11% ofadolescents.¹⁰ Apediatric study involving sev- eralAsiancountries showedan overall survival withgood prognosisof3.7%.¹³

The standardization of the CPAdata collection recom- mendedby the Utstein-styleallowed the identiﬁcation of variationsbetweencommunitiesandcountriesregardingthe healthcare system, survival chain quality, patient-related factors,andCPAdatacollection.

Thefactorsassociatedwithsurvivalinprehospitalpedi- atricCPAhavebeenthesubjectofmanystudiesandwillbe discussedbelow.

Age

Inpediatricpatients,mostCPAeventsoccurinthoseyounger than 1year (44---64%),^10,11,20 andthe incidence in this age rangeisclosetothatofadults.

A Swedish prospective study including adultsand children (n=40,503) observed, at shockable rhythms, higher survival rates after one month in those younger than 18 years (24.5%), intermediate in adults aged 18---35 years (21.2%), and lower rates in adults older than 35 years (13.6%; p<0.003), a pattern similar to that observed in non-shockablerhythms(3.8%,3.2%,and1.6%,respectively, p<0.0001).One-monthsurvivalrateswere2.6%inneonates, 7.8%inchildren,and24.5%inadolescentswhentheinitial rhythm was shockable. In non-shockable rhythms, one- monthsurvivalwas3.8%inchildren,3.2%inyoung adults, 1.6%in adults(olderthan 35years).²¹ Pediatricmulticen- terstudieshaveshownthesametrend,withlowersurvival ininfants(1.4---3.7%),followed bychildren(3.6---9.8%)and adolescents(8.9---16.3%).11,13,20,22

In Japan, a prospective observational study disclosed morefavorableoutcomesinchildren,whencomparedwith adults,withasurvivalrateof8%versus5% andgoodneu- rological function in 2% versus 1%, respectively. In the samestudy,survival withgoodneurologicalprognosis was observed in 1% of infants, 4% of children, and 11% of adolescents.¹⁰ Table1presentsthemaincharacteristicsof prehospitalCPAindifferentagegroups.10,11,15,19,21---28

The better survival rates observed in adolescents can be attributed to a set of factors, such as the higher occurrence in public places, greater likelihood of being witnessed,increasedprevalenceofVF(ventricularﬁbrilla- tion)/VTpulseless(ventriculartachycardia)initialrhythm,

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Fig.1 PediatricChainofSurvivaloftheAmericanHeartAssociation.³³

and increased chance of automatic external deﬁbrillator (AED)use.

AlthoughtheincidenceandoutcomesofprehospitalCPA differaccordingtoage, thevariablesassociatedwiththis observationarenotfullyunderstood.

Place of occurrence

SurvivalathospitaldischargeafterCPAthat occurredina prehospitalsettingisapproximatelythreetimeslowerwhen comparedwithin-hospitalCPA,due todelayedrecognition andtreatment.^17,29

MostpediatricprehospitalCPAeventsoccurathome,and theiroccurrenceinpublicplacesincreaseswithage,ranging from22%to45%inadolescents.^10,30

Somelocationsmayshowapeculiarsurvivalratedueto theavailabilityofAEDandtrainedteams.Astudycarriedout at40internationalairportsdiscloseda32%survivalratefor adults.³¹TheSãoPaulosubwaysystem,inBrazil,achieveda 43%survivalrateathospitaldischargeinadults,asigniﬁcant ﬁgureintheprehospitalsetting.³²

TheoccurrenceofCPAinpublicplaces,whicharemore likelytobe witnessed, associated withthe availabilityof AEDandcommunitytrainedinCPR,canpositivelyinﬂuence survival.

Witnessed CPA and early CPR

The key elements of the pediatric survival chain include an integratedsequence of events: prevention, early CPR, EMSactivation,advancedlife support(ALS),andpost-CPR care^33,34 (Fig.1).Despitetheincreasingemphasisonearly CPR,only15---40%ofprehospitalpediatricCPAindeveloped countriesundergosuchmaneuversinthecommunity,similar towhatisobservedadults.^4,10,24,30

Most pediatric prehospital CPAs occur at home^13,21,30; whentherearetrainedfamilymembers,thisisanopportu- nitytostartearlyCPR.PediatricCPAfollowedbyCPRprior tothearrivalofEMSarefactorsstronglyassociatedwithsur- vivalathospitaldischarge,withgoodneurologicalprognosis (OR4.74; 95% CI: 1.49---15.05).³⁵ Witnessed pediatric CPA occursin36---39.9%ofthecasesandCPRpriortothearrival oftheEMSoccursin49---49.2%ofcases.4,13,23,24,30,36,37

Theincreasedsurvivalofpatientswithchronicdiseases maybean opportunitytoraiseawarenessanddisseminate CPRtrainingin thecommunity, focusingonstrategic indi- viduals,suchasfamilymembers,withapossibleimpacton pediatricCPAprognosis.

Etiology

Unlikeadults,in whichcardiac causesarefrequent,³⁸ the main etiologies of prehospital CPA in children aresudden infantdeathsyndrome(20---60%),trauma(19---53%),andres- piratorycauses(4---41%).^4,19,35,39

InastudyanalyzingprehospitalpediatricCPAadmittedto theintensivecareunit(ICU),itwasobservedthatpatients who presented a cardiac etiology showed survival with a goodneurologicalprognosisin65%ofcases,incontrastto 39% when the etiology wasnon cardiac (OR 6.40; 95%CI:

1.65---24.76).³⁵

Sudden death is one of the most frequent causes in infants⁴⁰ and, in these circumstances, the cardiac cause is probably underestimated, since the cardiovascular etiology, such as channel opathies,⁴¹ which are hereditary diseasescharacterizedbyalterationinionchannelscausing greater susceptibilitytoarrhythmias,may bepresent and undiagnosed.²¹

Survival in pediatric trauma victims (n=2,299) is very low,around1.1%athospitaldischarge,andonly0.3%have agoodneurologicalprognosis.¹⁹Inturn,incasesofdrown- ing,survivalatdischargereaches22.7%,ofwhom6%have agoodneurologicalprognosis.^4,11Amongthevariablesthat affecttheoutcomeofdrowning,submersionduration,water temperature, and earlystart ofCPR arenoteworthy. Sur- vivalwithintactneurologicalfunction hasbeen described inprolongedsubmersioninfreezingwaters.⁴²

Althoughtheetiologycaninfluenceprognosis,thecause ofprehospitalCPAis oftenpresumedanddifficulttocon- firm.

Telephone EMS dispatcher-assisted CPR guidance

DespitetheimportanceofearlyCPRinthecommunity,only one-third to one-half receives CPR in prehospital CPA.⁴³ Thus, the role of the EMS dispatcher through telephone- basedCPRguidancemayberelevant.

An observational study on prehospitalpediatric CPA in Japan found that, when comparedwith itsabsence, spe- cialized telephone guidance increased the rate of CPR performed in the community (68.7% vs. 27.8%), mouth- to-mouth ventilation (43.6 % vs. 18.4%), and one-month survival(19%vs.11.2%);however,nosigniﬁcanteffectwas observed on the neurological outcome.⁴⁴ A more recent study in thesamecountry corroboratedprevious ﬁndings.

Telephone-basedguidanceincreasedCPR(OR7.51;95%CI:

6.60---8.57) and favorable neurological outcome after one

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Epidemiologyofpediatriccardiopulmonaryresuscitation 413 monthwhencomparedwithnon-CPRperformance(OR1.81;

95%CI:1.24---2.67).⁴³

Thus,astheCPRperformedinthecommunityisafunda- mentallinkinthepediatricsurvivalchain,telephone-based guidance has the potential to trigger early CPR and may increasesurvival,withagoodneurologicalprognosis.

Emergency medical service care

PrehospitalCPAcarebyEMSappearstobeassociatedwith longersurvival.^13,45 Apediatric studyobservedan associa- tionwithlongersurvivalafterinterventionsinaprehospital environment, such as ﬂuid administration (OR 1.73; 95%

CI:1.07---2.80)andattemptsviaintraosseousorintravenous route (OR2.40;95% CI:1.20---4.81).As for theacquisition ofadvancedairway,itwasnotassociatedwithsurvival(OR 0.69;95%CI:0.43---1.10),anddrugusewasassociatedwith worseprognosis(OR0.24;95%CI:0.15---0.39).²⁰Inturn,ina pediatricstudycarriedoutinAsiancountries,theacquisition ofadvancedairwaywaspositivelyassociatedwithsurvival athospitaldischargeinchildrenyoungerthan13years(OR 3.35;95%CI:1.23---9.13).¹³

Consequently,thereisstillnoconsensusonwhichmaneu- vers,inadditiontohigh-qualitychestcompressionsandAED use,shouldbepartofprehospitalCPR.Studyingeachofthe possibleprehospitalinterventionsthatmayimpactsurvival isdesirable,butdifﬁculttoperformduetothedifﬁcultyin obtainingthenumberofcasesofpediatricCPAwithstatis- ticalpower.

Rhythm

Non-shockable rhythms are those most often observed in prehospital pediatric CPA;^21,30,46 asystole is identiﬁed in 39---78%andPEA(pulselesselectricalactivity),in10---31%of patients.4,13,23,35,44

Shockable rhythms are present in approximately 35%

of adults²¹; their frequency is lower in pediatric patients and varies with age (5---11% in children and 19---21% in adolescents).^20,44 Shockablerhythm hasbeen identiﬁedas one of the factors strongly associated with survival in prehospitalCPA in adultsandchildren.10,19,21,23,30,35 A retrospective pan-Asian prehospital pediatric study involving 974children under17yearsalsoobservedthisassociation (OR20.29;95%CI:9.45---43.57).¹³

Although shockablerhythms,which areassociatedwith bettersurvival,areuncommon inthepediatric agegroup, thisage grouphashighersurvivalthan adults;the factors thatdeterminethisoutcomeremainunclear.

Early deﬁbrillation

Rapid deﬁbrillation is critical for the survival of patients with VF; consequently, the routine use of AED is indi- catedinallprehospitalCPAaccordingtotheresuscitation guidelines.^8,33,47Astudyincludingchildrenaged1---17years foundthatshockablerhythmswerelessfrequentinchildren youngerthan8yearsthaninadults(11.6%vs.23.7%),and theuseofAEDwas16.3%inchildrenyoungerthan8years

versus28.3%inadults.²⁸ Otherstudieshaveconﬁrmedthis observation.13,22,30,45

TheavailabilityofAED inpublicplacesassociatedwith basiclifesupport(BLS)trainingshowedastrongassociation withsurvival,withgoodneurologicalprognosisinchildren inaJapanese study(OR 5.13;95%CI:2.64---9.96)⁴⁴ andin anAustralianstudy (OR 4.74;95% CI:1.49---15.05). Inthis study,BLStrainingwasassociatedwithatenfoldincreasein CPRandAED useinthecommunity,andincreasedsurvival tohighwithgoodneurologicalprognosis,from42%to64%in thesameperiod.³⁵

Despitethe increasingacknowledgement of theimpor- tance of BLS and early deﬁbrillation, transposing the recommendationinto effective disseminationin the com- munityremainsamajorchallenge.

Quality of basic life support

The principles of high-quality BLS include: minimizing compressioninterruption,avoidinghyperventilation,main- taining adequate compression frequency and depth, and allowingfullchestreturn.⁴⁷Basedonthe2005resuscitation guidelines,⁴⁸ thereisanincreasingemphasisontheimpor- tanceof BLS,becausehigh-qualityCPRmaybeassociated withlongersurvival.^45,49---52

Inshockablerhythms, ahighcompressionfraction(pro- portionof timedevotedtochestcompression duringCPR) wasassociatedwithhighersurvivalinadults(OR3.01;95%

CI:1.37---6.58).⁴⁹Thedepthofthecompressions(higherthan 38mm) in adultswas associated with survival at hospital discharge(OR1.45;95%CI:1.20---1.76).⁵¹ However,mostof thesestudieswereperformedinadultsandinpediatricin- hospitalCPA.

Several aspects of BLS have been evaluated. A prehospital CPA study in adults evaluated the rate of chest compression and found an association with the return of spontaneouscirculation(ROSC);OR0.78;95%CI:0.66---0.92, p<0.003),but notwith survivalat hospital discharge(OR 0.82;95%CI:0.63---1.07,p<0.14).⁴⁹

A multicenter prospective study found several oppor- tunities for improvement in prehospital pediatric CPR, as it detected poor adherence (22---58%) to CPR quality parameters.⁴⁵ Another relevant parameter is appropriate ventilation,ashyperventilationreducedcoronaryperfusion (p=0.03)andsurvival(p=0.006),eveninteamstrainedin animalmodels.^53,54

Adequatedepthofcompressionswasobservedinonly58%

ofCPR inpediatric patients,andnoassociation withROSC wasobserved.⁴⁵Animalstudiessuggestthatchestcompres- sion discontinuation results in an abrupt fall in coronary perfusion,andseveralchest compressionsarerequired to resumeadequatecoronaryperfusionpressure.⁵⁵

Full chestreturn atthe end ofthe compressionallows the reduction of intrathoracic pressure, favoring preload andcoronaryperfusion,inadditiontoallowingpassiveair intake,fundamentalfactorstoachieveROSC.⁵⁶

Thereisevidencethathigh-qualityBLSisassociatedwith increasedsurvival;therefore,effortstoexpandopportuni- tiesforimprovementintheprehospitalsettingareessential.

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In-hospital CPA

ThestandardizationofthepediatricUtsteinstyleoccurred in 1995,⁵⁷ and encouraged the creation of CPR registries and databases. One example is the National Registry of Cardiopulmonary Resuscitation (NRCPR), which started in 2000tocollect prospectivedataatvarioushospitalsinthe United States,⁵⁸ withthe primary objective of improving CPR quality. This registry provided a robust database for thedevelopmentof evidence-basedguidelines,aswell as data comparison across hospitals and implementation of improvement strategies. In 2010, the NRCPR was incor- porated into the Get With The Guidelines----Resuscitation Registry (GWTG-R) program tofacilitate the registration, analysis,implementation,anddisseminationofthe guidelines,aswellasevidence-basedpractice.⁸

In-hospital pediatric CPA studies show a widevariabil- ityregardingprognosis,whichcanbeexplainedbyregional differences,studydesign,studiedpopulation,hospitalchar- acteristics and sector, rapid response team performance, andpost-resuscitationcare,amongothers(Table2).

TheUtsteinstylestimulatedtheresearchonin-hospital pediatric CPR, and the ﬁrst pediatric study applying this standardizationwasdevelopedinBrazil.⁵⁹ Inaprospective multicenter observational study that included adults and childreninemergencyservices,it wasobservedthatmost rhythmsduringCPAwerenon-shockableandsurvivalathos- pitaldischargewashigherinchildrenthaninadults(27%vs.

18%,OR2.29;95%CI:1.95---2.68).⁶⁰Inturn,amorerecent, multicenterretrospectivestudyusingthesamedatabaseas thepreviousstudyfoundthatsurvivalathospitaldischarge wassimilarbetweenadultsandchildren(23%vs.20%).⁶¹

Considering the different hospital sectors, survival at hospitaldischargewasobservedin13.7---47%inpediatricICU studies,^62---6412.8%inmulticenterstudiesinpediatricemer- gencyservices,⁶⁵and37---39.2%whenconsideringallhospital sectors.^66,67

Studies evaluatingsurvivalat hospitaldischargein less favoredcountriesarescarce.In India,survival at hospital dischargewas14.5%,with77.1%havingagoodneurological prognosis.⁶⁸InBrazil,adatabaseanalysisshowedasurvival rateof32.8%atdischargeinatertiaryuniversitypediatric hospital.⁶⁹

In a tertiary university hospital in Africa, withlimited resources, including shortage of trained staff, equipment (deﬁbrillator), medications, and ICU beds, mortality was 100%within24h.The infectious etiology (malaria,sepsis) associatedwith peculiarcomorbidities (HIV and malnutrition)contributedtothisscenario,whichimpairallpatient care(pre-,during,andpost-CPR).⁷⁰

Table2 describestheoutcomesof in-hospitalpediatric CPA.29,37,60,63,64,68---86 One-yearsurvival rangedfrom11.1 to 34.5% amongthe studies.59,68,71---74 Several factors maybe associatedwithin-hospital pediatric CPAsurvival andwill bediscussedbelow.

Age

The age range appears to inﬂuence the incidence of in- hospitalCPA. Aretrospective cohort study found ahigher incidenceininfantsunder1year,whencomparedwithchil-

drenandadolescents(0.79/1,000vs.0.56/1,000).Despite the higher incidence in this age group, infant mortality (46.8%)wassigniﬁcantlylowerthanintheothergroups: 1 to2years,3to5years,6to11years,and12to17yearsof age(58.8%,57.7%,64.8%,and70%,respectively).¹

A multicenter study carried out in a pediatric ICU observedasurvivalrateof27%athospitaldischargeinthe neonatalperiod,36%ininfants,19%inchildrenaged1to8 years,and16%inchildrenolderthan8years.⁶³ Lowersur- vivalwasobtainedinapediatrictertiarycenter,with17.8%

ininfants, 7.5%inchildren aged1to4 years,and3.4% in children older than 8 years.⁶⁹ Both studies showed lower survivalwithadvancingage.

Analyses of long-term survival arescarce. A multicen- terstudyindicatedaone-yearsurvivalof52.4%inchildren youngerthan1year,43.4%inthoseaged1to4years,41.7%

in those aged 5 to 12 years, and 41% in those aged >13 years.⁸⁷

Therefore, age appears to be a determining factor in prognosis;however,thefactorsassociatedwiththisobser- vationareyettobeclariﬁed.

CPR duration

Some authors have observed that the duration of pediatric in-hospital CPR was inversely related to survival.42,59,82,84,87---89 Anegative association wasobserved between CPR duration and survival (OR 0.95; 95% CI:

0.91---0.98).Inprospectivestudy carriedoutina pediatric tertiary hospital in Brazil using the Utstein style.⁵⁹ A pediatricprospectivestudyintheICU observedsurvivalat hospitaldischarge withCPR lastinglessthan 3min of 66%

andlastinglongerthan30minof28%.⁸⁴ Amulticenterreg- istryshoweda2.1%perminutedropinsurvivalathospital dischargewithCPR lastinglessthan15minanda1.2%per minute drop in the favorable neurological outcome.⁸⁸ In turn,studiesincludingprolongedpediatricCPA(longerthan 30---35min) showed a favorable neurological prognosis in 60---89%ofcases.^84,88

The longer the CPR duration, the longer the low car- diacoutputperiod,withpotentialorgandamage.Increased survival at hospital discharge with favorable neurological prognosis despite prolonged duration has a multifactorial cause;thebestquality-CPRandadvancesinpost-CPA care arelikelythedeterminingfactors.

Time and day of the week

The inﬂuence of the time and day of week on the out- comeofCPAhasbeenevaluatedbysomeauthors.Astudy inadultsobservedhighersurvivalat daytimeonweekdays (20.6%;95%CI:20.3---21%),whencomparedwithnighttime andonweekends(17.4%;95%CI:16.8---18%);OR1.15;95%CI:

1.09---1.22).⁹⁰Apediatricmulticenterstudyalsofoundlower survivalratesathospitaldischargeatnighttime,whencom- paredwithdaytime(OR0.88;95%CI:0.80---0.97;p<0.007).⁹¹ The difference in the patient care processes between daytimeandnighttime,suchaslowernurse/patientratio, presenceoflessexperiencedprofessionals,greaterpossibil- ityoferror,andreducedpsychomotorskillperformancemay explaintheseresults.⁹⁰

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Epidemiologyofpediatriccardiopulmonaryresuscitation415

Table2 Characterizationofstudiesonin-hospitalpediatricCPA.

Author Country Year Studytype Numberof

patients

Place ROSC(%) Highsurvival(%) Survivalwithgood neurological prognosis(%)

One-year survival (%)

Slonin⁶² UnitedStates 1997 Prospective 205 ICU NA 13,7 NA NA

Suominen⁷¹ Finland 2000 Retrospective 118 Hospital 62.7 19.5 12.7 17.8

Reis⁵⁹ Brazil 2002 Prospective 129 Hospital 64 16.2 15 14.7

Guay⁷² Canada 2004 Retrospective 203^a Hospital 73.8 40.8 23.4 26

Rodríguez-Nu˜nes³⁷ Spain ²⁰⁰⁶ Prospective 116 ICU 59.5 35.3 31 34.5

Tibballs⁷³ Australia 2006 Prospective 111 Hospital 76 36 NA 34

Nadkarni⁶⁰ UnitedStatesandCanada 2006 Prospective 880 Hospital 52 27 18 NA

deMos⁷⁵ Canada 2006 Retrospective 91 ICU 82 25 18 NA

Meaney⁶³ UnitedStates 2006 Prospective 411 ICU 48.9 21.4 14 NA

Wu⁷⁶ Taiwan 2009 Retrospective 316 Hospital 72.2 20.9 15.5 NA

Meert⁷⁷ UnitedStates 2009 Retrospective 353^b Hospital ND 48^a 46^a NA

Olotu⁷⁸ Kenya 2009 Prospective 114^c Hospital ND 15.7%PCR ND NA

Berens⁷⁹ UnitedStates 2011 Retrospective 257 Hospital 56.8 31.1 19.8 NA

Girotra²⁹ UnitedStates 2013 Retrospective 1031 Hospital 34.8 61 NA

López-Herce⁸⁰ Spain 2014 Prospective 200 Hospital 74 41 77.9 NA

Berg⁸¹ UnitedStates 2013 Prospective 5870events Hospital 72 39 95 NA

Zeng⁷⁴ China 2013 Prospective 174 Hospital 62.1 28.2 86 12.1

RIBEPCI⁸² Multinational 2013 Prospective 502 Hospital 69.5 39.2 34.8 NA

Straney⁸³ Australia,NewZealand 2015 Prospective 677 ICU NA 63.7 NA NA

Rathore⁶⁸ India 2016 Prospective 314 Hospital 64.6 14 77 11.1

Berg⁸⁴ UnitedStates 2016 Prospective 139 ICU 65 45 89 NA

Gupta⁸⁵ UnitedStates 2017 Retrospective 154 ICU 100 66,6 94,3 NA

Andersen⁸⁶ UnitedStates 2017 Prospective 182 Hospital ND 53,8 NA NA

Sutton⁶⁴ UnitedStates 2018 Prospective 164 ICU 90 47 75,7 NA

Shimoda-Sakano,Annals⁶⁹ Brazil 2018 Prospective 220 Hospital 70,1 28,7 NA NA

Edward-Jackson⁷⁰ Malawi(Africa) 2019 Prospective 135 Hospital 6 0 0 0

(UpdateandadaptationbyLopezHerce,withpermission).NA,notavailable.

a Includesapneapatients,55CPApatients.

b NotincludingallCPApatients,onlythosewithsustainedROSC.

c IncludesnewbornsandchildrenwithapneaandCPA.

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Hospitalinpatientunitsneedtodevelopmechanismsthat allow the improvement and standardization of CPR care regardlessofthetimeanddayoftheweek.

Drug administration

Epinephrineis the most signiﬁcant drug usedduring CPR.

Despiteitsfrequentuse,itseffectiveness,safety,andade- quatedosage arenotfullyknown.⁹² Epinephrinehasbeen used in CPR since 1960 due to the effect of increased coronary and cerebral perfusion pressure and increased possibility of ROSC and survival at hospital admission.⁹³ However, it might reduce microcirculatory ﬂow, favor arrhythmias,anddecreasecerebralbloodﬂow.⁹²

Studiescomparingepinephrineversusplacebousefound thatthedrugincreasesROSC(RR3.09;95%CI:2.82---3.89;

n=8,469) and survival at discharge (RR 1.44; 95% CI:

1.11---1.86;n=8,538).^92,94,95However,whenconsideringthe neurologicalprognosis,nodifferencewasobservedbetween theconventionaldoseofepinephrineandplacebo(RR1.22;

95%CI:0.90---1.92).^94,95

Another aspect of interest was the use of high doses compared to conventional doses of epinephrine in pedi- atricCPA.^96,97 Inaprospectiverandomizedpediatricstudy conducted in Brazil, it was found that the use of high- dose epinephrine after the conventional dose reduced 24h survival in children (OR for death: 7.9; 97.5% CI:

0.9---72.5;p=0.08).⁹⁶ ACochranereviewanalyzingtheuse ofepinephrineinpediatricCPA,whenevaluatingtheuseof thestandarddoseofepinephrinecomparedwithhighdoses inpediatricCPA,failedtoobservesigniﬁcantdifferencesin ROSC(RR1.13;95%CI:0.73---1.73),24h survival(RR1.04;

95%CI:0.76---1.43),andsurvivalatdischarge(RR1.54;95%

CI:0.17---13.66).⁹²

Thetimingofﬁrstdoseadministrationhasbeenthesub- jectofarecentstudyandappearstobeofrelevanceforthe outcomes.⁹⁸ A pediatric in-hospital CPA study found that, withnon-shockablerhythms,delayedepinephrineadminis- trationwasassociatedwithlowerchanceofROSC (RRper minuteofdelay:0.97;95%CI:0.96---0.99),reducedsurvival athospitaldischarge(RRperminuteofdelay:0.95;95%CI:

0.93---0.98), andneurological prognosis worsening (RRper minuteofdelay:0.95;95%CI:0.91---0.99).⁹⁹

The interval between epinephrine doses during CPR is anotherimportantaspect. Apediatric study¹⁰⁰ obtaineda highersurvival at hospital discharge in patients receiving epinephrine at intervals longer than three to ﬁve min- utes (longerthanﬁve andshorter thaneightminutes,OR 1.81; 95% CI: 1.26---2.59 and 8---10min, OR 2.64; 95% CI:

1.53---4.55); 3---5min is the interval recommended by the current2015resuscitationguidelines.

The number of epinephrine doses during PCR was inversely associated with shorter 12-month survival. The administration of more than four epinephrine doses was independentlyassociatedwithshorterone-yearsurvival(OR 0.52;95%CI:0.30---0.92).⁸⁷

EpinephrineremainsthemostcommonlyuseddruginCPA forincreasing therateof ROSC; however,itsinﬂuence on long-termsurvivalandneurologicalprognosishasyettobe proven.

Monitoring at the time of the event

Pre-CPR monitoring inﬂuences CPA survival in adults and children.Aretrospectivestudyinadultscomparedsurvival at discharge in places with and without telemetry (cardiac) monitoring and found rates of 20.8% versus 16.1%, respectively.⁹⁰Apediatricstudyalsoobservedalowermor- talityratewhenCPAoccurredinamonitoredenvironment (OR0.51;95%CI:0.30---0.87,p=0.01).⁸⁶

The occurrence of CPA in emergency services, that is, in places withlower monitoring, is more frequent in less favoredcountries,probablyduetothescarcityofICUbeds.

Pediatric CPA in the ICU has better survival at discharge whencomparedtootherhospitalsectors(OR0.38;95%CI:

0.15---0.86),⁸²possiblyduetoappropriatemonitoring,resul- tinginearlydetectionandinterventioninthepresenceof clinicaldeteriorationsigns.

InJapan,therewasahigherincidenceofCPAinpediatric wards comparedtothe Americandatabase (27%vs. 14%), demonstratingashortageofICU beds;however,therewas nosigniﬁcantdifferenceinoutcome.¹⁰¹

Monitoringallowstheearlydiagnosisandearlyonsetof CPR,withalikelyfavorableimpactontheoutcomeofpedi- atricCPA.

CPR quality monitoring

The assessment of the quality and performance of CPR hasallowedadvancesinscienceandclinicalpractice.The use of new technologies has allowed the monitoring of CPRparametersduringcare,andtheiruseinclinicalprac- ticeisrecommendedwheneveravailable.¹⁰²CPRmonitoring categories can be classiﬁed into physiological (patient- dependent)andCPRperformance(resuscitator-dependent).

CPRguidelinesrecommenduniformityofchestcompres- sions according toage range, but this approachdoes not assesstheindividualresponsetoCPRefforts.⁵²Thus,adjust- ingCPRqualitytophysiologicalparametersthroughinvasive hemodynamicassessment(invasivebloodpressureandcen- tralvenous pressure monitoring) andexpired CO2 (EtCO2) throughcapnographymayincreasesurvival.^102---107

DataonpediatricCPRqualityarelimitedsofar,andrec- ommendationsarebasedonexpertconsensus.¹⁰²Thevalue of EtCO2appearstobedirectly associatedwithpulmonary ﬂow, cardiac output and survival. The consensus on CPR qualityrecommendscontroloftheperformancetoachieve EtCO2>20mmHg,basedonexperimentalstudiesandlimited datainadults.¹⁰²Arecentreviewhasemphasizedthatthe EtCO2’sevolutionvaluecanbemorereliablethanitsstatic value duringCPR.¹⁰³ Therefore,althoughallpediatricCPR guidelinesrecommendtheuseofcapnographyduringPCAas ameasureofcompressionquality,nopediatricstudieshave establisheditstruerole.

Observationalstudiesanalyzingdiastolicbloodpressure suggestan associationwithcoronaryperfusionpressure.A recent pediatric publication suggeststhat chest compres- sionsmaytargetminimaldiastolicpressureandcorrespond to a performance measure that may determine CPR outcome.¹⁰⁴Inthisstudy,survivalathospitaldischargewas 70% morefrequent whenthe diastolicblood pressurewas greater than or equal to 25mmHg in infants and greater

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Epidemiologyofpediatriccardiopulmonaryresuscitation 417 thanorequalto30mmHginchildrenolderthanoneyear.

Thus,basedonanimalstudiesandlimiteddatainadultsand children,itisreasonabletousephysiologicalparametersto monitorandmaximizeCPRquality.¹⁰⁵

High-quality CPR is also considered one of the deter- minants of survival in both prehospital and in-hospital settings.¹⁰⁶ A study inadults found thatwhen chest com- pressionswerelessthan100/minute,therewasareduction from 72% to 42% in ROSC.¹⁰² In turn, a pediatric study found that compression rates of 80---100/min (lower than thatrecommended bycurrent guidelines),whencompared with100---120/min,ledtohighersurvivalat discharge(RR 1.92;95%CI:1.13---3.29,p=0.017)andbetterneurological prognosis(RR2.12;95%CI:1.09---4.13,p=0.027).⁶⁴

ThecontrolofCPRphysiologicalandqualityparameters ispromisingandmayrepresentachangefromconventional care,wherepre-establishedqualityparametersarerecom- mended.Furtherstudiesarerequiredtoclarifytherealrole ofCPRqualityparametersandtheirrespectivetargetval- ues.

Initial rhythm

The initial rhythm has been associated with the prehospital^10,30 and in-hospital^60,74,87 CPA outcome. In astudythatanalyzedtheﬁrstdocumentedrhythm,survival at discharge in shockable rhythms was higher in children thaninadults,24%versus11%(OR2.73;95%CI:2.23---3.32), respectively.⁶⁰

Althoughshockablerhythmsarenotfrequentinchildren, the presence of VF or pulseless VT as the initial rhythm representedhigherchancesof sustainedROSC(more than 20min; 64.7% vs. 39.1%, p<0.046) and higher survival at hospitaldischarge(58.8% vs.21.7%,p<0.02)⁸⁹ when com- paredtoasystoleandPEA.One-yearsurvivalwas64.7%in thosewithshockable rhythms, 56.5%inPEA,and16.7%in asystole.⁸⁷

Thebetterprognosisinshockablerhythmsinvolvestheir greater reversibilitypotential. Therefore,focusingefforts onearlyCPR,shockablerhythmrecognition,andrapiddeﬁb- rillationshouldremainapriority.

Immediate cause and underlying disease category

In-hospital pediatric CPA occurs mostly in patients with chronic diseases, accounting for 71% to 90.9% of cases.59,82,87,89 The chronic diseasecategory may beinﬂu- encedby theanalyzedregionandmaybeassociatedwith higherorlowermortality.InIndia,forinstance,malnutrition wasfoundin65%ofpediatricCPRs.⁶⁸

The prognosis of CPR appears to be inﬂuencedby the associated chronic disease. In an international multicenter prospective pediatric study, onco hematological (OR 3.33;95%CI:1.60---6.98)andneurological(OR5.19;95%CI:

1.49---18.73)diseasesledtohighermortality.⁸²

Childrenwithcongenitaloracquired heartdiseaserep- resentahigherriskgroupforCPA.^85,108Amulticenterstudy in cardiac pediatric ICUs showed that the prevalence of CPA in non-surgical vs. surgical heart diseases was 50%

higher,andsurvivalwaslower(37.7%vs.62.5%,p<0.0001, respectively).¹⁰⁸

Regardingthemostcommonpreexistingcausesofpedi- atric CPA, an American registry highlighted respiratory (58%), shock (36%), and heart failure (31%) as the most prevalentcauses.⁶⁰ In contrast,astudy in Indiaidentiﬁed sepsis(71%),respiratorydiseases(39.5%),andneurological diseases(31.5%)asthemostprevalentcauses.⁶⁸

A prospective Brazilian study carried out in a tertiary pediatric hospital found respiratory diseases as the main cause(61%),followedbyshock(29%);⁵⁹amorerecentstudy atthesameinstitutionfoundachangeinthisdistribution, withadeclineinrespiratorycauses(56%)andanincreasein shock(43%).⁶⁹

Somestudieshaveshownthatconditionsprecedingthe pediatricCPAwereassociatedwithincreasedmortality,such ashypotension(OR3.26;95%CI:1.89---5.92,p<0.001)and sepsis(OR2.45;95%CI:1.52---3.97;p<0.001).⁸⁶Otherstudies reinforcedthisﬁndingbyobservingthattheuseofvasoac- tivedrugs^68,89(OR4.47;95%CI:1.72---9.37;p<0.001)⁶⁸and shockprecedingtheCPA^69,82,86(OR2.46;95%CI:1.52---3.97, p<0.001)⁸⁵indicatedaguardedprognosisatCPR.

Variations in the etiology of CPA may reﬂect improve- mentsin respiratorydiseasepreventionandcare,andthe association of chronic diseases results in highermortality fromshock. Studyingthe roleofeach categoryof chronic diseaseintheincidenceandprognosisofCPRisnotaneasy task,asit requires large multicenterstudies witha large numberofpatients.

Prognostic trend for in-hospital pediatric CPA

Pediatricin-hospitalCPAappearstoexhibitdistinctbehav- iors over time. When analyzing the trend of pediatric in-hospital CPA in the United States, an increase was observedintheincidenceofCPA,from0.57/1,000in1997 to1.1/1,000in2012(p<0.05),withadeclineinmortality over the same period, from 51% to 40% (p<0.05).¹ Con- sideringthe intensive care setting, including32 American services,survivalathospitaldischarge afterpediatricCPA was13.7%inthe1990s⁶² and22%inthe2000s.⁶³ Asimilar trendwasobservedinothercountries,suchasSpain,where asigniﬁcantimprovementinsurvival(from25.9%to41%in 10years)wasobserved,mostofthemwithagoodneurolog- icalprognosis.^25,89 Data froma Brazilian tertiarypediatric hospitalobservedanincreaseintherateofROSC(64---70%) andsurvivalathospitaldischarge(19---32.8%)in15years.^59,69 The trend towards increased survival in pediatric CPA inseveral servicesand countriesis probablythe resultof multipleeffortsinvolvingimprovedqualityofBLS,ALS,and post-CPAcareasaresultoftheadvancementofCPRscience.

Conclusion

PrehospitalpediatricCPAisarareevent,withshortersur- vivalcomparedtothein-hospitalsettingandhasaguarded neurologicalprognosis.

Conversely,pediatricin-hospitalCPAhasalongersurvival than prehospital CPA due to early recognition associated withhigh-qualityBLS,appropriateALSandpost-CPRcare.

In recent years, a trend towards improved pediatric CPA

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survivalhasbeen observed insome communitiesandhos- pitals,andsurvivalwithgoodneurologicalprognosisismore frequentinchildrenthaninadults.

TheavailableepidemiologicaldataonpediatricCPAare particularly concentrated in countries in North America, Europe,Asia, andAustraliathatparticipateinlargeinter- nationalregistries.ImprovementinpediatricCPAoutcomes dependsoneffortstoclarifyfactorsassociatedwithbetter survivalwithgood neurologicalprognosis. Toincrease the knowledgeinthisarea,epidemiologicalstudiesinpediatric hospitalslocatedindisadvantagedareasremainaresearch priorityandarefundamentalfortheimplementationofpre- vention strategies, improvements in CPR performance, in additiontoallowingtheanalysisofpossibleregionalvaria- tionsofCPRepidemiologyamongthedifferentservicesand countries.

Conﬂicts of interest

Theauthorsdeclarenoconﬂictsofinterest.

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