Rev. Bras. Anestesiol. vol.65 número5

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RevBrasAnestesiol.2015;65(5):384---394

REVISTA

BRASILEIRA

DE

ANESTESIOLOGIA

OfficialPublicationoftheBrazilianSocietyofAnesthesiology

www.sba.com.br

REVIEW

ARTICLE

Perioperative

morbidity

and

mortality

in

the

first

year

of

life:

a

systematic

review

(1997---2012)

Dora

Catré

a,b,∗

,

Maria

Francelina

Lopes

b,c

,

Joaquim

Silva

Viana

d

,

António

Silvério

Cabrita

b

a_Centro_Hospitalar_{Tondela-Viseu,}_Viseu,_Portugal

b_Faculdade_de_Medicina,_Universidade_de_Coimbra,_Coimbra,_Portugal

c_Hospital_Pediátrico,_Centro_Hospitalar_e_{Universitário}_de_Coimbra,_Coimbra,_Portugal

d_Faculdade_de_Ciências_da_Saúde,_Universidade_da_Beira_Interior,_Covilhã,_Portugal

Received20November2012;accepted20March2013 Availableonline27July2015

KEYWORDS

Earlymortality; Morbidity:cardiac arrest;

Perioperativecritical events/adverse events;

1-Yearold/1-month oldchildren

Abstract

Backgroundandobjectives: Althoughmanyrecognizethatthefirstyearoflifeandspecifically

theneonatalperiodareassociatedwithincreasedriskofanestheticmorbidityandmortality, therearenostudiesdirectedtothesepediatricsubpopulations.Thissystematicreviewofthe scientificliteratureincludingthelast15yearsaimedtoanalyzetheepidemiologyof morbid-ityandmortalityassociatedwithgeneralanesthesiaandsurgeryinthefirstyearoflifeand particularlyintheneonatal(firstmonth)period.

Content: ThereviewwasconductedbysearchingpublicationsinMedline/PubMeddatabases,

andthefollowingoutcomeswereevaluated:earlymortalityinthefirstyearoflife(<1year) andinsubgroupsofdifferentvulnerabilityinthisagegroup(0---30daysand1---12months)and theprevalenceofcardiacarrestandperioperativecritical/adverseeventsofvarioustypesin thesamesubgroups.

Conclusions:Thecurrentliteratureindicatesgreatvariabilityinmortalityandmorbidityinthe

agegroupunderconsiderationandinitssubgroups.However,despitetheobvious methodo-logicalheterogeneityandabsenceofspecificstudies,epidemiologicalprofilesofmorbidityand mortalityrelatedtoanesthesiainchildren inthefirst yearoflifeshow higherfrequencyof morbidityandmortalityinthisagegroup,withthehighestpeaksofincidenceintheneonates’ anesthesia.

∗_{Corresponding}_author.

E-mail:[email protected](D.Catré). http://dx.doi.org/10.1016/j.bjane.2013.03.025

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Perioperativemorbidityandmortalityinthefirstyearoflife 385

PALAVRAS-CHAVE

Mortalidadeprecoce; Morbidade:parada cardíaca;

Eventoscríticose adversos

perioperatórios; Crianc¸asdeum ano/ummêsdeidade

Morbimortalidadeperioperatórianoprimeiroanodeidade:revisãosistemática (1997-2012)

Resumo

Justificativaeobjetivos: Emboramuitosreconhec¸amqueaidadeinferioraumanoe

especifi-camenteoperíodoneonatalestejamassociadosamaiorriscodemorbimortalidadeanestésica, nãoexistemestudosdirigidosaessassubpopulac¸õespediátricas.Estarevisãosistemáticadas publicac¸õescientíficasdosúltimos15anostevecomoobjetivoanalisaroperfilepidemiológico damorbimortalidaderelacionadacomaanestesiageralecirurgianoprimeiroanodeidadee emparticularnoperíodoneonatal(primeiromêsdeidade).

Conteúdo: A revisão foi conduzida por pesquisa de publicac¸ões nas bases de dados

Med-line/PubMed.Foramavaliadososseguintesdesfechos:mortalidadeprecoce noprimeiro ano de idade(<1A) eem subgrupos dediferente vulnerabilidadenestafaixa etária(0-30 diase 1-12meses)eprevalênciadeparadacardíacaeeventoscríticos/adversosperioperatóriosde diversostiposnosmesmossubgrupos.

Conclusões: Aliteraturacorrenteindicagrandevariabilidadenosíndicesdemortalidadee

mor-bidadenafaixaetáriaemanálise,bemcomonosseussubgrupos.Noentanto,apesardaóbvia heterogeneidade metodológicaedaausênciadeestudos específicos,osperfis epidemiológi-cos demorbimortalidaderelacionadacomaanestesiadecrianc¸asnoprimeiro anodeidade mostramfrequênciamaisaltademorbimortalidadenessafaixaetária,comosmaiorespicosde incidêncianaanestesiadeneonatos.

Introduction

Information onmorbidity and mortality inpediatric anes-thesiaisabundant,butscattered.Althoughmanyrecognize that age <1 year and specificallythe neonatal periodare associatedwithhigher risk ofanesthetic complications,1,2

therearenostudiesaimedatthisagegroup.Availabledata

arescatteredin studiesthatcovera widerrangeofages,

with reports differing from the results in these pediatric

groups.

Theimprovedsurvivalincongenitalpathologies,aswell

asthedevelopmentofnewsurgicaltechniquesinpediatrics,

ledtoanincreaseinthenumberofsurgeriesperformedin

childrenunderoneyearofage,manyofwhichinextremely

vulnerable infants.3 _The _anesthesia _of _pediatric _patients

youngerthan 1 yearhas veryspecific characteristics, and

the results of pediatric studies in older children are not

necessarilyapplicabletothem.

Althoughtheriskofanestheticcomplicationsis

presum-ably associatedwith population characteristics, thestudy

of morbidity and mortality related to anesthesia care in

the pediatric population younger than one year has

spe-cialrelevanceforitsfrequencyandconsiderableimpacton

patients’health.Thecharacterizationofthe

epidemiologi-calprofileofmorbidityandmortalityinthisagegroup,asan

instrumentofhealth carequalityevaluation,can improve

anesthesia in this group of very particular characteristics

and provide a starting point for reducing morbidity and

mortality.1,4---6

This systematicreviewofscientificstudiespublishedin

thelast15yearsaimedtoanalyzetheepidemiological

pro-fileofmorbidityandmortalityrelatedtogeneralanesthesia

in the first year of age, and particularly in the

differ-entvulnerablesubgroups:firstmonth and fromoneto12

months.

Methods

Weperformedasystematicsearchofthestudiespublishedin

Medline/Pubmed(http://www.ncbi.nlm.nih.gov/pubmed/)

from 1 January 1997 to 31 October 2012 to find

orig-inal articles on mortality or morbidity associated with

the perioperative period of children under one year of

age. The following keywords were used in the search:

anesthesia-related and mortality and anesthesia-related

andmorbidity.Fromthetitleorabstractofthepotentially relevantarticles,weusedthePubMedfunctionrelated arti-cles.Additionalreferencesfromthisresearchandrelevant

studiescitedwereincluded.

Thesearchwaslimitedtohumanstudiesandthelast15

years.

Alltitles,abstracts,andfulltextsofpotentiallyrelevant studieswereevaluatedforeligibilitybasedontheinclusion

orexclusioncriteriapreviouslydetermined.

Inclusioncriteriawerestudies evaluatingtheincidence

ofearly mortalityor perioperativecardiac arrestor criti-cal/adverseeventsofvarioustypes,asdefinedbydifferent authors,withinformationregardingthespecificsubgroupof childrenunderoneyearofage(group<1Y).Whenages0---30

daysand1---12monthswerespecified,thesedatawerealso

collected.

Exclusioncriteriawerestudieslimitedtoasingleregional

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386 D.Catréetal.

Datawerecollectedindependentlybytwoauthorsofthis

study(DCandMFL).

Of each selected article, data on the type of study,

geographicarea,number of cases,number of anesthesia,

typeofsurgery,andperioperativemortalityandmorbidity

werecollected.Regardingmortality,dataonthemortality

rateper10,000anesthesiaswerecollectedandtheperiods

in which death occurred: in the operating

room/post-anesthesiacare unitorin thepostoperativeperiodatany

timewithin30days.Regardingmorbidity,dataontherate

ofperioperativecardiacarrestwerecollected.Inaddition

tothiscriticalevent, weharvested informationregarding

critical/adverse events of various types (defined by the

respectiveauthors)whenevermentionedintherevised

pub-lication.

Results

Theinitialsearchforpublications,limitedtohumansandthe

mentionedperiod,originated 104 and144articlesfor the

anesthesia-related and mortality and anesthesia-related

andmorbiditycombinations,respectively.Afterreadingthe

titleor abstractof these articles and other relevant

sur-veyedbytherelatedarticlesfunctionandcitedreferences,

the selection included 20 articles reporting perioperative

mortality or morbidity related to anesthesia in children

underoneyearofage.Fullanalysisofthesearticlesledto theexclusionofonesystematicreview.1_Thus,_our_study_data

representacompilationofinformationfrom19articles.2,7---24

In16articlesofincidence,2,7---21_two_reported_series_in_which

patientswerealsoincludedinpreviousarticles:thestudyby Braz200617_included_data_from_Braz₂₀₀₄18_and_the_study_by

Kawashima200215 _included_data_from_Morita_2001.7_These

data analysis was made to complement the information,

butnottoduplicate.Theremainingthreepublications22---24

refertomulticenterdatabase ofreportedcases.All

stud-iesarelevelBof scientific evidence,according toOxford

classification.25

DataonmortalityarepresentedinTables1and2anddata

onmorbidityinTables3and4.Table5compilesmortality

profilesandcardiacarrests inthedifferentagesubgroups

withinthefirstyearofage.

Mortalityinchildreninthefirstyearofage

Mortality rates reportedin the literature included in the

studyarepresentedintablesoneandfive.Five10---14_of_the

eightstudies in Table 1 have informationon overall

mor-tality per 10 thousandanesthesia in the first year of age

(<1Yor0---12M).There isagreatvariability, from11.4 to

38.9per10,000anesthesiasduringsurgeryandimmediate

postoperativeperiod(an average of30 deaths per10,000

anesthesias,calculatedonthebasis oftwoseries10,12 _that

totaled13,634anesthesia)and35.1to59.7per10,000 anes-thesiasuptothefirst24hafteranesthesia(an averageof

53deaths per10,000 anesthesias,calculatedon thebasis

oftwolargeseries[1,141]thattotaled20,661anesthesia).

Themortalityratewithinthefirsttwodaysofanesthesia,

assessedin astudy13 _involving _pediatric_patients _up_to₁₈

yearsofage andwith4863anesthesiasinthefirstyearof

age, was 18.5 per 10,000 anesthesias. In another study14

involvingpediatricpatientsupto18yearsandwith15,255

anesthesiasinthefirstyearofage,themortalityraterelated

toanesthesiaat30dayswas135per10,000anesthesias.

Theanalysisoftheseresultsallowshighlightingthe

fol-lowingfeatures:

1. The definition of death during the intraoperative and

earlypostoperativeperiodsorrelatedtoanesthesiahas

noconsensusintheliterature,butregardlessofthe crite-riaused,thestudiesinvolvingmultipleagegroupsfound

highermortalityrateinchildrenunderoneyear ofage

whencomparedtoolderchildren.

2. DatapresentedinTable1indicatingveryhighmortality

ratesinthestudybyChanetal.,9_Van_der_Griend_et_al.,14

andFlicketal.10_should_be_read_in_this_context_of_criteria

variability, asit refer to the totalanesthetized cases, includingcardiacsurgery,and,inthecaseofChanetal.,9

transplants.VanderGriendetal.14_and_Flick_et_al.10_also

report in their publications the mortality rate in

non-cardiacsurgery, which drops from59.7to 39.7/10,000

anesthesiasinthefirst24hoursinthestudybyVander Griendetal.14_and_from_38.9_to_5/10,000_anesthesias_in

thestudybyFlicketal.10

Mortalityinsubgroupsofchildrenundertheageof 1year(0---30daysand1---12months)

Tables1and5haverelevantdataonmortalityrateduring

thefirstmonthofageandfrom1to12months,andTable2

showsthestudieswhichindicatethecauseofdeath.

Five7---14 _of _the _eight _selected _studies _to _evaluate _the

mortalityratecontaindatafor analysisof thisoutcome in

subgroupsfirstmonth(0---30days)and12monthsofage.

Thedeathratesduringsurgeryandpostoperativeperiod

of anesthesias in neonates and children aged one to 12

monthsanalyzedinastudy10_that_involving_children_up_to₁₈

years,with1451anesthesiasinneonatesand7807

anesthe-siasinchildrenagedoneto12monthswere,respectively,

144.7and19.2per10,000anesthesias.Inthefirst24hours, themortalityratespresentedintwostudies9,14_ranged_from

180.1to288per 10,000anesthesiasin neonatesandfrom

32.2to129per10,000anesthesiasinchildrenagedoneto

12months.Mortalityratesinthefirstsevendaysanalyzed

intwostudies7,8_ranged_from_26.94_to_74.10_and_from_5.91

to 6.63 per 10,000 anesthesias, respectively, in neonates

andchildrenaged1---12months.Inanotherstudy14_involving

pediatricpatientsupto18yearsofageandwith2831

anes-thesiasinneonatesand12,424anesthesiasinchildrenaged

1---12months,the30daysmortalityrateswere,respectively,

367.4and82.1per10,000anesthesias.

Thefollowingaspectsarehighlighted:

1. As in theanalysis ofmortality ratein thefirst year of

age,theanalysisofmortalityratesinthetwosubgroups

ofthis agegrouprevealsthe samemethodological

dif-ferencesandthe need for criticalevaluation fromthe

standpointthisvariability.Theanalysisoftheseprofiles showsthatthepeakriskofmortalityisconsistentinthe

anesthesiagroupofneonates,comparedwiththegroup

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P

erioperative

morbidity

and

mortality

in

the

first

year

of

life

387

Table1 Incidenceofintraoperativeandearlypostoperativemortalityinchildrenunder1yearofage.

Author/s(year);typeof publication;periodof investigationand location

Deaths includedin datacollection

Numberofprocedures, maximumage

Overall mortalityinthe study/10,000 anesthesias

Subgroupsunder1yearofage

Age Numberof

anesthesias

Incidence/10,000 anesthesias

Moritaetal.(2001)7_; R-M;1999;Japan

First7days 732,788anesthesias atallages

ND 0---30d 3509 74.10

1---12M 13580 6.63

First7days 910,757anesthesias atallages

ND 0---30d ND 26.94

1---12M ND 5.91

ChaneAuler(2002)9_; R-1C;1998---1999;Brazil

First24hours 82,641anesthesiasat allages

51 0---30d ND 288

1---12M ND 129

Flicketal.(2007)10_; R-1C;1988---2005;USA

ORandPACU 92,881anesthesiasin childrenunder18

6.8 0---30d 1451 144.7

1---12M 7807 19.2

Geral<1Y 9258 38.9

Bunchungmongkoletal. (2007)11_;_P-M; 2003---2004;Thailand

First24h 25,098anesthesiasin childrenupto15years

15.9 0---12M 5406 35.1

Ahmedetal.(2009)12_; R-1C;1992---2006; Pakistan

ORandPACU 20,216anesthesiasin childrenunder18

3.46 0---12M 4376 11.4

Bhartietal.(2009)13_; R-1C;2003---2008; India

First2days 12,158anesthesiasin childrenunder18

10.7 0---12M 4863 18.5

VanderGriendetal. (2011)14_;_R-1C; 2003---2008;Australia

First24hours 10.1855anesthesiasin childrenunder18

24h:13.4 24h

0---30d 2831 180.1

1---12M 12,424 32.2

Geral<1Y 15,255 59.7

30d:34.5 30d:0---30d 2831 367.4

1---12M 12,424 82.1

Geral<1Y 15,255 135.0

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388 D.Catréetal.

Table2 Mortalitycontextinchildrenunder1yearofagereportedintheliteratureoverthelast15years.

Author/s(year);typeofpublication Agegroup Number ofdeaths

Age/reportedcontext

Reportsconcerningdeathsrelatedtoanesthesia

Kawashimaetal.(2002)15_;_R-M _0---12_M ₀ _No_deaths_related_to_anesthesia Bunchungmonkoletal.

(2009)2_;_P-M

0---30d 1 1d/bradycardiaafterinadequateoxygenation duetopneumothoraxonpostoperative thoracotomyduetotracheoesophagealfistula 1---12M 1 6M/bradycardiainthecontextofapparent

hypovolemiainemergingcraniotomy Ahmedetal.(2009)12_;

R-1C

0---30d 0 Nodeathsrelatedtoanesthesia

1---12M 1 8M/inadequateventilationafterextubation VanderGriendetal.

(2011)14_;_R-1C

0---30d 1 13d/congenitalheartdisease

1---12M 2 4M/ex-prematurewithtrisomy21and

congenitalheartdisease

4M/degenerativeneurologicaldisease

Reportsconcerningoverallintraoperativeandearlypostoperativedeaths

Kawashimaetal. (2002)15_;_R-M

0---12M 26 ND/21deathsrelatedtopreoperative complications(17fromcardiovascularevents, including11congenitalheartdisease) ND/5deathsrelatedtosurgery Flicketal.

(2007)10a_;_R-1C

0---30d 4(in17 years)

2.11and25d/massivebleeding

1d/duetopericardialtamponadeforcentral catheterization

1---12M 0 Nodeathinnon-cardiacsurgery

R-M,retrospectivemulticenter;P-M,prospectivemulticenter;R-1C,retrospective1center;M,month;d,day;ND,unavailable informa-tion.

a_Information_regarding_non-cardiac_surgery.

2. InthedataanalysisofKawashimaetal.,15_regarding_the

compilation and analysis of data presented by Morita

etal.7 _for_the _annual_study _of_mortality_and_morbidity

inJapanin1999,mortalitywashigherinchildrenunder

onemonth ofage.However,mortalityinchildren aged

between one and12 months,even though higherthan

that ofolder children,hasbeen supersededby thatof

individualsagedbetween66and85yearsormore.

3. Although several studies refers to the most frequent

causesofdeathandriskfactors,mostofthemdoesnot

contain or analyzes this data in different age groups;

therefore, specific datafor childrenunderoneyear of

agearerareandtheexistingdatagenerallyreferonlyto

theanesthesia-relateddeaths.Thisinformationis

com-piledinTable2.

Perioperativemorbidity

Regardingperioperativemorbidity,studiesshow great

dis-parity between the available data. Some authors have

chosentoanalyzethecardiacarrestsin theperioperative

period(Table3), whileothers evaluatedawider rangeof

critical/adverseevents(Table4).

Perioperativemorbidityinthefirstyearofage

InTable 3, six10---13,16,17 _of _the_eight _listed _articles_contain

informationontherateofcardiacarrestper10,000 anesthe-siasinthefirstyearofage.Ofthesesixarticles,fivereferto

theoperatingroomandpost-anesthesiacareunitandoneto

thefirst24h.Table5presentstheprofileofcardiacarrests inthedifferentsubgroupsoffirstyearofage.

Itwasnotedthat therateofcardiac arrestper 10,000

anesthesiasintheoperatingroomandpost-anesthesiacare

unit ranged from8.916 _to _87.117 _(average _of _38.6 _cardiac

arrests per 10,000 anesthesias, calculated based on five

majorseries10,12,13,16,17 _totaling_25,392_{anesthesias);}_and_in

onestudy11 _of_the_first₂₄_h, _the_rate_was_48.1_per _10,000

anesthesiasinauniverseof5406anesthesias.

Therateofperioperativecritical/adverseeventsof

dif-ferenttypesassociatedwithanestheticprocedures(Table4)

rangedfrom4.6%to30.8%.

Wehighlightthefollowingaspectsofthecriticalanalysis ofTables3and4andtherelatedliteraturedata:

1. Aswithmortality,thecriteriausedtocalculatethe inci-denceofcardiacarrestorcritical/adverseeventsvaried.

Thereisthereforeadiscrepancyinthevaluespresented

thatmustbeinterpretedinitscontext.Forexample,the incidenceofcardiacarrestreportedbyFlick etal.10 _is

total,includingcardiacsurgery.Inthisstudy,inchildren

underoneyear ofage, theincidenceof cardiacarrest

consideringonlynon-cardiacsurgerywas8.7per10,000

anesthesias,one-fifthofthetotalincidence.

2. In all studies found, the incidence of cardiac arrest

andcritical/adverseeventsofvarioustypeswashigher

in children aged less than one year than in older

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P

erioperative

morbidity

and

mortality

in

the

first

year

of

life

389

Table3 Incidenceofperioperativecardiacarrestinchildrenunder1yearofage.

Author/s(year);typeof publication;periodof investigationand location

Cardiacarrest Numberofprocedures, maximumage

Overallincidencein thestudy/10,000 anesthesias

Age Numberof anesthesias

Incidence/10,000 anesthesias

ND 732,788anesthesiasat

allages

ND 0---30d 3509 54.1

1---12M 13,580 8.8

allages

ND 0---30d ND 28.3

1---12M ND 8.54

Muratetal.(2004)16_; P-1C;2000---2002; France

ORandPACU 24,165anesthesiasin childrenupto15years

3.3 <1Y 3681 10.9

Brazetal.(2006)17_; P-1C;1996---2005;Brazil

ORandPACU 53,718anesthesiasatall ages

34.6 0---30d 846 177.3

1---12M 2368 55.1

Geral<1Y 3214 87.1

Flicketal.(2007)10_; R-1C;1988---2005;USA

8.6 0---30d 1451 158.5

1---12M 7807 23.1

Geral<1Y 9258 44.3

Bunchungmongkoletal. (2007)11_;_P-M; 2003---2004;Thailand

First24hours 25,098anesthesiasin childrenupto15years

19.9 <1Y 5406 48.1

Ahmedetal.(2009)12_; R-1C;1992---2006; Pakistan

ORandPACU 20,216anesthesiasin childrenupto18yearsa

4.95 <1Y 4376 18.3

Bhartietal.(2009)13_; R-1C;2003---2008; India

22.2 <1Y 4863 35

R-M,Aretrospectivemulticenter;P-1C,Aprospective1center;R-1C,retrospective1center;P-M,Aprospectivemulticenter;ND,unavailableinformation;OR,operatingroom;PACU, post-anesthesiacareunit;d,days;M,months.

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390

D.

Catré

et

al.

Table4 Incidenceofperioperativecritical/adverseeventsinchildrenunder1yearofage.

Author/s(year);typeof publication;periodof investigationandlocation

Occurrence period

Numberofprocedures, maximumage

Overall incidencein thestudy

Age Numberof anesthesias

Incidência

Tayetal.(2001)19_;_P-1C; 1997---1999;Singapore

ND 10,000pediatriccases 2.78% <1Y 1022 8.6%

Moritaetal.(2001)7_;_R-M;_1999; Japan

allages

ND 0---30d ND 1.68%

1---12M ND 0.48%

Moritaetal.(2002)8_;_R-M;_2000; Japan

allages

ND 0---30d ND 0.7%

1---12M ND 0.42%

Muratetal.(2004)16_;_P-1C; 2000---2002;France

3.1%atOR 4.8%atPACU

<1Y 3681 3.6%atOR

1.47%atPACU Edomwonyietal.(2006)20_;_P-1C;₁₂

months,yearunspecified;Nigeria

ORandPACU 270anesthesiasin childrenunder16years

24% 0---30d 15 26.7%

1---12M 69 6%---8.7%

Bunchungmongkoletal. (2007)11_;_P-M;_2003---2004; Thailand

First24h 25,098anesthesiasin childrenupto15years

1.9% <1Y 5406 4.6%

Samakéetal.(2010)21_;_P-1C; Marc¸o-setembro2004;Mali

ND 107anesthesiasin

childrenupto12years

39% <1Y 107 30.8%

P-1C,prospective1center;R-M,retrospectivemulticenter;P-M,prospectivemulticenter;ND,unavailableinformation;OR,operatingroom;PACU,post-anesthesiacareunit;Definition ofcriticaleventoradverseevent,Ref.19 _---_respiratory,_{cardiovascular,}_and_related_to_the_equipment,_drugs,_regional_anesthesia,_and_others,_including_seizures,_deaths,_and _dental

injuries;Ref.7,8_---_cardiac_arrest,_severe_hypotension,_severe_hypoxemia;_Ref.16_---_{cardiovascular,}_{neurological,}_related_to_regional_anesthesia_and_others,_including_anaphylaxis,_malignant

hyperthermia,doseerror,prolongedneuromuscularblockade,hypoorhyperthermia,vomiting,postoperativehemorrhage,andequipmentfailure;Ref.20 _---_{cardiovascular,}_respiratory,

neurologicalandgastrointestinal(postoperativenauseaandvomiting);Ref.11 _---_pulmonary_aspiration,_symptomatic_esophageal_intubation,_desaturation_for_more_than₃_minutes,

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Table5 Epidemiologicalprofilesofmorbidityandmortalityinsubgroupsunder1yearofage.

Age Outcomes Rateper10,000 anesthesias

Numberofstudiesfor calculation(totalnumberof anesthesias)

Variationper 10,000 anesthesias

Mortality

<1Y OR/PACU 30 2(13,634) 11.4---38.9

First24h 53 2(20,661) 35.1---59.7

First2days 18.5 1(4863) 18.5

First30days 135 1(15,255) 135

0---30d OR/PACU 144.7 1(1451) 144.7

First7days ND 2(ND) 26.94---74.10

First30days 367.4 1(2831) 367.4

1---12M OR/PACU 19.2 1(7807) 19.2

First7days ND 2(ND) 5.91---6.63

First30days 82.1 1(12,424) 82.1

Cardiacarrest

<1Y OR/PACU 38.6 5(25,392) 8.9---87.1

First24h 48.1 1(5406) 48.1

0---30d OR/PACU 165.4 2(2297) 158.5---177.3

1---12M OR/PACU 30.5 2(10,175) 23.1---55.1

OR,operatingroom;PACU,post-anesthesiacareunit;d,day;M,month;ND,unavailableinformation.

3. Thefrequencyofcardiacarrestattheagegroupreferred to in our study is also relevant compared to older children. In the studies available, 50%---80% of cardiac arrestsinchildren occurredinpatientsunderoneyear ofage.10---13,16---18 _Similarly,_Morray_et_al.22 _in_their_study

basedonregistrationdatafromPOCA(Pediatric

Periop-erativeCardiac Arrest Registry)stated that more than

halfofcardiacarrestsreportedbetween1994and1997

athospitalsintheUnitedStatesandCanadaoccurredin

childrenunderoneyearofage(169per289children).In thisstudy,ageasanindependentfactoroftheassociated

pathologywasnotpredictiveofmortalityaftercardiac

arrest.

4. Bhanankeretal.23_showed_in₂₀₀₇_an_update_of_the_POCA

Registryinwhichitisnoticeabletherelativepercentage

decreaseof cardiac arrests reportedin children under

oneyearofagecomparedtodataofpreviousyears

pre-sentedbyMorrayetal.22 _However,_without_information

onthenumber ofanesthesiaperformed in hospitalsin

question, it is not possible to calculate and compare

incidences.

5. MacLennanetal.24_identified₆₀₆_critical_events_reported

inchildrenbetween 2006and2008 intheUnited

King-dom,ofwhich102(16.8%)inchildrenunderoneyearof

age.Asit isacompilationof reportedcasesof several

hospitals,itisalsonotpossibletocalculatetheincidence inthispopulation.

Perioperativemorbidityinsubgroupsofchildren under1yearofage

InTable3,four7,8,10,17_of_eight_articles_contain_information

regardingtherateofcardiacarrestper10,000anesthesias

duringthefirstmonthofage(0---30days)andbetweenone

and12months.Table5shows theepidemiologicalprofiles

ofcardiacarrestinsubgroups0---30daysand1---12months. Inthefirstmonthofage,therateofcardiacarrestranged

from 28.3 to 177.3 per 10,000 anesthesias and in 1---12

monthsitvariedfrom8.54to55.1per10,000anesthesias.

Inbothstudies10,17_with_complete_data_for_the_calculation_of

thenumberofcasesofperioperativecardiacarrest,amean

of165.4cases ofcardiacarrestoccurred inthe operating

roomand post-anesthesia care unity per 10,000

anesthe-siasinthefirstmonthofage,foraglobaluniverseof2297

anesthesias,andameanof30.5casesper10,000

anesthe-siasinchildren1---12months,foraglobaluniverseof10,175 anesthesias.

Forthefirstmonth ofage,therate ofcritical/adverse

eventsofvarioustypes(Table4)rangedfrom0.7to26.7%

ofanesthesiasandfor1---12months,itrangedfrom0.42to

8.7%ofanesthesias.

The highlights of the critical analysis for data of

Tables3and4andrelatedliteraturearethefollowing:

1. As for the group of children in the first year of age,

the criteriausedtocalculate the incidenceof cardiac

arrest or critical/adverse events in subgroups of 0---30

daysand1---12monthsvaried.Itwasnoticeddiscrepancy

inthevalues,whichmustbeinterpretedinitscontext.

Forexample,theincidenceofcardiacarrestpresented

by Flick et al.10 _is _total, _including _cardiac _surgery. _In

this study,in children underone year of age, its

inci-denceincardiacsurgerywasmuchhigher(434.8/10,000

anesthesias) than in non-cardiac surgery (39.4/10,000

anesthesias).

2. Bhanankeretal.23_found₉₃_cardiac_arrests_reported

(9)

392 D.Catréetal.

upto18years,ofwhich21inneonatesand53inchildren

aged1---12months,inPOCARegistrybetween1998and

2004.

Etiologyandcontextofperioperativemorbidityin childrenunder1yearofage

Theetiologyandcontextofcardiacarrestsinchildrenunder oneyearofagearemostlyspecifiedonlyincasesrelatedto anesthesia.

Thus,in thestudy of Ahmed etal.,12 _of _the_eight

car-diacarrestsinchildren underoneyearofage,threewere

attributed toanesthetic causes, notably by hypovolemia,

inadequateventilation(citedintheanalysisof mortality),

and bradycardia after succinylcholine administration. All

wereconsideredpreventable.

In his study of 9 years, Braz etal.17 _reported _that _all

cardiacarrestsrelatedtoanesthesiainchildrenunderone

yearofagewereduetoinefficientventilationandoccurred

inpatientsASAIIIorIV.Nodeathinthestudywasrelated

toanesthesiaandallcasesofcardiacarrestdueto

respira-toryeventoccurred inpatientswithsignificantassociated

pathology.

ThesevencardiacarrestsidentifiedbyFlicketal.10_were

due to hypoxemia (n=1), massive bleeding (n=3),

possi-ble air embolism (n=1), complications related tocentral

catheterization(n=2),ofteninaggravatingcontextsas illus-tratedbythephysicalstatusASAIVorVinfivecases.

In the study by Bunchungmongkol et al.,2 _in _addition

tothe two cases resulting in death previously described,

caused by insufficient oxygenation and hypovolemia, the

remainingfivecardiacarrestsrelatedtoanesthesiain

chil-drenunderoneyearofageweremotivatedbymedication

errors(n=3)andinadequateoxygenation(n=2).

InJapaneseannualstudies,7,8,15_the_incidence_of_cardiac

arrestinchildrenunderoneyearofage(andmoreexpressive

inneonates)wasmainlyattributedtocoexistingpathology.

Nocardiacarrestinneonateswasassociatedwith

anesthe-sia.Itis worthnotingthatin casesof1999, followingthe

occurrenceofcardiacarrest,80.8%ofneonatesdied.This

showsthatcardiovascularresuscitationinthisagegroupis exceptionallydifficult.15

Regardingthevariouscritical/adverseeventsinthe

pop-ulationunderoneyearofage,theliteraturedataareonce

againwidelydispersed,duetothewiderangeofdata

col-lectedandbecausethepopulationinstudiesisnorestricted

tothatagegroup.

In the assessment of 1000 pediatric anesthesias, Tay

etal.19_found_an_incidence_of_2.8%_of_laryngospasm_in

chil-drenunderoneyearofage,significantlyhigherthaninolder children.

Murat etal.16 _and_Edomwonyi_et_al.20 _reported_in_their

studiesahigherfrequencyofcardiacandrespiratoryevents

inchildren under oneyear of age either in the operating

roomor post-anesthesiacareunit. Thesecond study adds

thatadverseeventsoccurredmorefrequentlyduring

anes-theticinduction.

Ontheotherhand,Bunchungmongkoletal.11_report_that

inthisagegroup criticalevents occurredmorefrequently

during anesthesia. Desaturation was the most common

event. In this study, children under one year of age had

significantly higher incidence of delayed esophageal

intu-bationdetection(0.17%),desaturation(2.2%),reintubation

(0.42%),cardiacarrest(0.65%),death(0.65%),and

medica-tionerror(0.07%).

Discussion

Inthissystematicreview,weemphasizethemainfindings:

(1)thehigherincidencesofmortalityandmorbidityin

chil-dren underoneyearof ageundergoinggeneralanesthesia

comparedwitholderchildren;(2)theincreasedriskinthose

incidences in children undergoing surgeryin the neonatal

period;(3)thehighfrequencyofcardiacarrestsinpatients underoneyearofageamongthetotalcardiacarrestsin chil-dren;(4)thelackofstudiescenteredintheneonatalperiod andfirstyearofage;(5)thegreatvariabilityof

methodolo-giesforthestudyofthesameconcepts.

Althoughthereareseveralstudiesofmorbidityand

mor-tality in anesthetic-surgical setting with incidence data

on pediatric population under one year of age and even

neonatal, this systematic review allowed the compilation

of several existing information that would allow both its

joint analysis and comparison with pre-existing empirical

knowledgeandtheidentificationofunansweredquestions.

Although the included studies were level B of scientific

evidence,mostofthemincludedtensofthousandsof

anes-thesiasintheirseries.

Regarding the various studies methodology, a

signifi-cant difference in the data collected definition is linked

to the period in which the incident occurred:

intraop-erative, operating room and post-anesthesia care unit,

the first 24h, the first two days, the first postoperative

week or month. On the other hand, there is no

consen-sus in the literature regarding the definition of death

and morbidity in the anesthetic/surgical context.

Sev-eral authors report death related to anesthesia, but it

is also determined in several ways: related to the

anes-thesiologist role or anesthetic technique, factors under

the anesthesiologist control, and factors such as surgical

and anesthetics, among others. Given its multifactorial

nature, dataanalysis may bemore informative ifall

fac-tors are considered rather than just trying to emphasize

the ones potentially relatedto anesthesia. Also,risk

pre-vention is more likelyif more importanceis givento the

occurrenceofdeathandmorbiditythroughoutthe

periop-erative process, and not just tothe risk of anesthesia in

particular.14

Also,the discussion of causes and risk factorsis often

limited toa wide range of ages.Of data reported in the

literature specifically related to children less than one

yearold,mortalityandmorbidityintheanestheticcontext

seemtobemorerelatedtocardiovascularandrespiratory

complications, which is consistent with the physiology of

thisage group.This trendseemstoreplacethedeaths of

olderstudies,mostlyrelatedtotheanestheticdrug,often

attributedtohalothane,myocardialdepressantdrug

espe-cially in younger children with congenital heart disease,

which,however,fellintodisuse.22,23,26_With_the_use_of_new

andsaferdrugs,deathsbegantobeevidencedbybleeding,

inadequatefluidtherapy,andrespiratoryproblems.Lossof

(10)

Because the circulating volumeis smaller, these patients

aremoresensitivetoinadequatehydration,bothexcessive

and insufficient. That age is a risk factor for respiratory

complications for twomain reasons: increasedperipheral

collapsetrendduetoincreasedchestwallcomplianceand

increased vagal tone with quick response of apnea and

laryngospasmtoirritation of receptorspresent in the

air-waysbysecretions,trachealintubation,andaspiration.The

resultinghypoxia is at that ageclosely relatedto cardiac

arrest.

In general,thepediatricseriesshowan increased

inci-dence of cardiacarrests, 1.4---4.6 per 10,000 anesthesias,

comparedwithonecaseper10,000inadultseries.27_Within

thefirstyear,ourstudyshowsamuchhigherincidence,with

aparticularlyhighproportionofcasesintheneonatalage

(165.4per10,000anesthesias).

The technical complications found related to central

lines placement, although of unknown incidence in the

perioperative setting, are well known in other settings,

notablyin pediatric intensivecare studies,which are

jus-tifiedbytheheartanatomyinthefirstmonthsoflife,with

thinnerwalls moresusceptibletotrauma.28 _Some _authors

recommendtheuseofultrasoundtoincreasethetechnique

safety.28

A common clinical implication to several studies in

the literature, whether directed to pediatric

anesthe-sia mortality or morbidity, is the guidance that pediatric

anesthesia,especiallyforyoungerchildren,shouldbe

per-formed by anesthesiologists with experience in this age

group.1,4---6,12,14,22,29

The global data analysis of pediatric cases of broader

agegroupsisnotnecessarilyapplicabletoanesthesiainthe

neonatalperiodandbeforethefirstyearofage.Therefore,

largemulticenterrandomizedstudiesspecificfortheseages

areneeded,inordertominimizeconfoundingfactorsand

biases,andthusadjusttheclinicalpracticemorecorrectly toincreasesecurity.

Conflicts

of

interest

Theauthorsdeclarenoconflictsofinterest.

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