Changes over time in 30-day survival and the incidence of shockable rhythms after in-hospital cardiac arrest - A population-based registry study of nearly 24,000 cases.

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Clinical

paper

Changes

over

time

in

30-day

survival

and

the

incidence

of

shockable

rhythms

after

in-hospital

cardiac

arrest

-

A

population-based

registry

study

of

nearly

24,000

cases

Anna

Adielsson

a,

*

,

Therese

Dja¨rv

b,1

,

Araz

Rawshani

c

,

Stefan

Lundin

a

,

Johan

Herlitz

d

a

DepartmentofAnaesthesiologyandIntensiveCareMedicine,SahlgrenskaUniversityHospital,Bla˚ Stra˚ket5,SE-41345Gothenburg,Sweden

b

DepartmentofMedicine,K2,SolnaKarolinskaInstitutet,SE-17177Stockholm,Sweden

c_Department_of_Molecular_and_Clinical_Medicine,_University_of_Gothenburg,_Institute_of_Medicine,_Sahlgrenska_Academy,_SE-413₄₅_Gothenburg,

Sweden

d_The_Centre_for_Pre-hospital_Research_in_Western_Sweden,_University_College_of_Bora˚s,_SE-501₉₀_Bora˚s,_Sweden

Abstract

Objective:Todeterminechangesovertimein30-daysurvivalandtheincidenceofshockablerhythmsafterin-hospitalcardiacarrest,froma countrywideperspective.

Methods:PatientinformationfromtheSwedishRegistryforCardiopulmonaryResuscitationwasanalysedinrelationtomonitoringlevelofwardand initialrhythm.Theprimaryoutcomewasdefinedassurvivalat30days.Changesinsurvivalandincidenceofshockablerhythmswerereportedperyear from2008to2018.Also,epidemiologicaldatawerecomparedbetweentwotimeperiods,2008 2013and2014 2018.

Results:Inall,23,186uniquepatients(38.6%female)wereincludedinthestudy.Themeanagewas72.6(SD13.2)years.Adjustedtrendsindicatedan overallincreasein30-daysurvivalfrom24.7%in2008to32.5%in2018,(onmonitoringwardsfrom32.5%to43.1%andonnon-monitoringwardsfrom 17.6%to23.1%).Theproportionofpatientsfoundinshockablerhythmsdecreasedoverallfrom31.6%in2008to23.6%in2018,(onmonitoringwards from42.5%to35.8%andonnon-monitoringwardsfrom20.1%to12.9%).Amongthepatientsfoundinshockablerhythms,theproportionofpatients defibrillatedbeforethearrivalofcardiacarrestteamincreasedfrom71.0%to80.9%.

Conclusions:Inan11-yearperspective,resuscitationinin-hospitalcardiacarrestinSwedenwascharacterisedbyanoverallincreaseintheadjusted 30-daysurvival,despiteadecreaseinshockablerhythms.Anincreasedproportion,amongthepatientsfoundinashockablerhythm,whowere defibrillatedbeforethearrivalofacardiacarrestteammayhavecontributedtothefinding.

Keywords:In-hospitalcardiacarrest,Cardiopulmonaryresuscitation,Defibrillation,Survival,Epidemiology

Abbreviations:CPR,cardiopulmonaryresuscitation;IHCA,in-hospitalcardiacarrest;IQR,interquartileranges;OHCA,out-of-hospitalcardiacarrest; SD,standarddeviation;SMD,standardisedmeandifference.

* Correspondingauthor.

E-mailaddresses:anna_adielsson@hotmail.com(A.Adielsson),therese.djarv@ki.se(T.Djärv),araz.rawshani@gu.se(A.Rawshani),

stefan.lundin@gu.se(S.Lundin),johan.herlitz@hb.se(J.Herlitz). 1

Address:DepartmentofMedicine,K2,SolnaKarolinskaInstitutet,SE-17177Stockholm,Sweden.

https://doi.org/10.1016/j.resuscitation.2020.10.015

Received23April2020;Receivedinrevisedform7October2020;Accepted13October2020 Availableonlinexxx

Available

online

at

www.sciencedirect.com

Resuscitation

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Introduction

Asubstantialproportionofdeathsrelatedtocardiacdiseaseoccurin hospitals.Themortalityrateinpatientsaffectedbycardiacarrestin healthcareunitsishigh,andsurvivalisstronglydependentonthe locationoftheeventwithinthehospital.1,2_The_survival_rate_of_patients

onwardswithmonitoringfacilitiescanbeuptotwiceashighasitison wards without monitoring facilities.3 More advanced surveillance facilitatesthepromptrecognitionofcardiacarrest,resultinginalarger proportion of witnessed cardiacarrests and a shorter time from collapsetotreatment.4

Inapreviousstudyconductedinasingletertiaryhospital,we concludedthat thetreatment ofin-hospital cardiacarrest (IHCA) was characterised by a more rapid start of treatment, over 20 years.3Therewas asignificantincreasein 30-daysurvival,from 44%to56%,onwardswithmonitoringfacilities.Onwardswithout these facilities, there was a substantial decrease in shockable rhythmsovertime,from46%to26%.Thereisaknowledgegapwith regardto changesincharacteristicsand outcomeafter IHCAon monitoring and non-monitoring wards in recent decades from a countrywideperspective.

Theaimofthisstudywasthereforetoexplorefurtherwhether similar changes had taken place in a countywide perspective in Sweden.Theprimaryobjectivewastodescribechangesin30-day survivalandchangesintheproportionofpatientsfoundinshockable rhythmsafterIHCAinSwedenbetween2008and2018.

Inordertoexplorepossiblemechanismsbehindeventualchanges in survival, we also describe patient characteristics and various aspects of resuscitation during twotime periods.The latterdata represent secondary objectives and should only be regarded as hypothesis-generating.

Methods

TheSwedishRegistryforCardiopulmonaryResuscitationstartedin 2005andisanationalqualityregisterwith thehighestdegree of certification, including IHCA and out-of-hospital cardiac arrests (OHCA).TheregistryemploysstandardisedUtstein-styledefinitions forallvariablesandoutcomes.5_At_{participating}_hospitals,_designated

personnel are responsible for the registration of the information associatedwithcardiacarrest,inasecureonlinesystem.Thedataare collectedintwosteps,attheinitialcardiacarresteventandmorethan 30dayslater.Inthefirststep,baselineinformation,e.g.locationand timeoftheevent,initialrhythm,delaystovariousactions,treatment givenandsurvivalafterresuscitation,isprospectivelyrecordedbya nurseorphysicianattendingtheevent.Inthesecondstep,follow-up data,e.g.co-morbidities,probableaetiologyofthecardiacarrestand 30-daysurvival data,are retrospectively recorded bya nurse or physicianassociatedwiththeregister.

Studydesignandpopulation

We analysed all IHCA registered in the Swedish Registry for CardiopulmonaryResuscitation,from1January2008to31December 2018.Inall,71of73(97%)hospitalswithcardiacarrestteamsin Swedenparticipated.Thenumberofparticipatinghospitalsincreased from45in2008to71 in2018.Thehospitalsrangedinsize from generalprimary-levelhospitalswithfewerthan50bedsto

tertiary-levelhospitalswithmorethan800beds.Theinclusioncriterionwasa cardiacarrestinwhichCPRordefibrillationwasattempted.Patients youngerthan18yearsofagewereexcluded.

Thestudypopulationwassubdividedintofourgroupsaccordingto monitoringfacilitiesontheward(non-monitoringvsmonitoringwards) andinitialrhythm(shockablevsnon-shockablerhythm)atthetimeof the cardiac arrest. Each groupwas furtherstratified in twotime periods,2008 2013and2014 2018inordertogettwogroupswith equal sizeintermsofthenumberofparticipants.Epidemiological data, includingage, gender,co-morbidities (myocardialinfarction, heartfailure,stroke,diabetes,respiratoryinsufficiency,cancerand renaldysfunction),time,locationandcircumstances ofthearrest, treatmentgivenanddelays,survivalimmediatelyafterthe resuscita-tionattempt,survivalat30days,oneyearandduringlongterm follow-up,wereanalysedandcomparedbetweengroups.

Definitionofvariables

“Cardiacarrest_”wasdefinedastheneedforCPRordefibrillation.The term “in-hospital” refersto allcardiac arrest occurring within the hospitalperimeter.“CPR”,includingbasiclifesupportandadvanced lifesupport,isperformedaccordingtotheEuropeanResuscitation Councilguidelines.6_When_a_cardiac_arrest_is_identified,_medical_staff

callanemergencytelephonenumberandacardiacarrestteam,ledby trainedhealthcareprofessionals,isimmediatelyactivated.

Healthcare facilities were defined as “academic” or “non-academic”hospitalsdependingonwhethertherewasaffiliationtoa medicalschooloradegree-grantinguniversity.Tenofthe participat-inghospitalswereacademichospitals.Healthcareunitsweredivided intowardswith_{“monitoring”}and_{“non-monitoring”}facilities,depending on the availability of continuous surveillance. Monitoring wards includeintensivecareunits,coronarycareunits,coronary angiogra-phy laboratories,operatingtheatres andemergencydepartments. Theremainingwards,includingintermediatewards,aredefinedas non-monitoringwards.Thefirstdocumentedrhythmofthecardiac arrestisdividedinto_{“shockable”}and_{“non-shockable”}rhythm,based ontheindicationfordefibrillationornot.7Previousmedicalhistorywas obtained from the patients’ medical records, based on formerly specifieddefinitions.Apriorhistoryofmyocardialinfarctionreferstoa myocardial infarctionpreceding thearrestby72hormore.Heart failureincludesallformsofheartfailure,exceptforpulmonaryoedema withinonehourbeforethearrest.Previousstrokecomprisesboth haemorrhagicandischaemicstrokebeforethecurrenthospitalisation period.Diabetesincludesbothtype1andtype2diabetes.Respiratory insufficiency includes all typesof respiratory insufficiency withor withouttheneedforaventilator.Cancerreferstoanypreviousor presentmalignancy,regardlessofseverity.Renaldysfunctionwas definedasanestimatedglomerularfiltrationrate(eGFR)of<60mL/ minusingtherevisedLund-Malmoformula.8

Validationofthereporteddata

Validationhasbeenperformedat34hospitals,comprisingatotalof 1338patients,whereregisterdatawerecomparedwithhospitalcase recorddata.Fromthepremisesofthisvalidation,informationabout theplaceofIHCAandsurvivalwasconsistentwithsourcedatain99% ofcases.Similarly,informationaboutwitnessedstatuswasconsistent withsourcedatain96%ofcases,aswellasinformationonthetypeof thefirstrhythm,whichwasconsistentwithsourcedatain94%of cases.

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Statisticalmethods

Baseline characteristics are reported usingmeans and medians, alongwithstandarddeviations(SD)andinterquartileranges(IQR), respectively. Standardisedmeandifferences (SMD)wereusedto comparegroups,andlogisticregressionwasusedtocalculatethe adjustedprobabilityof30-daysurvival.Adjustmentwasmadeforage, sexand calendaryear.TheKaplan-Meierestimatorwas usedfor delineatingsurvivalcurvesinrelationtocalendaryear,andthe log-ranktestwasusedtotestfordifferences insurvivalinrelationto calendaryear.Duetoarelatively lowfrequency ofmissingdata, completecaseanalyseswereperformedthroughoutthestudy.Data onage,sex,calendaryearandtypeofwardwascomplete.Dataon initialrhythmwasmissingin7.6%,whichwedeemedasacceptable. Also,previousqualitycontrolshavenotrejectedtheassumptionthat dataaremissingatrandom.AllanalyseswereperformedinRversion 4.0.2(RFoundationforStatisticalComputing).

Ethicalapproval

ApprovalwasobtainedfromtheethicalreviewboardattheUniversity ofGothenburg,Sweden,2017-11-06,referencenumber692-17.

Results

Duringthestudyperiod,23,186uniquepatientssufferedatotal of 23,950IHCA.Atotalof54.9%ofIHCAoccurredonwardswithout monitoringfacilities.Ashockablerhythmattheinitialelectrocardiogram recordingwasfoundin26.3%ofthetotalcases.Mencollapsedmore ofteninashockablerhythmcomparedwithwomen,withaproportionof 69.5%.Overall30-daysurvivalfortheentirestudypopulationwas30.0 %, with highersurvivalfor men(31.3 %) comparedwithwomen (27.9%). Theoverallmeanagewas72.6,SD13.2years,withpatientson non-monitoringwardsbeingolder;74.0,SD13.0years,comparedwith; 70.9,SD13.3years,onthemonitoringwards.Patientsfoundina shockablerhythmwereyounger;70.6,SD12.6years,thanthosefound inanon-shockablerhythm;73.3,SD13.3years.

VariousaspectsofIHCAaredescribed,trendchangesyearby yeararedemonstratedforadjustedsurvivalat30days,overalland

depending on the monitoring level of the ward and the initially registered rhythm, includingthe proportionofpatients foundin a shockablerhythm.Furthermore,changesinpatientcharacteristics andvariousaspectsofresuscitationbetweentwotimeperiodsare compared dependingon themonitoringlevelofthewardandthe initiallyregisteredrhythm.

Survival

Theoveralladjusted30-daysurvivalincreasedfrom24.7%in2008to 32.5% in2018. Amongpatientssuffering anIHCAon monitoring wards,theadjusted30-daysurvivalincreasedfrom33.5%in2008to 43.5% in 2018, and among patients suffering an IHCA on non-monitoringwards,theadjusted30-daysurvivalincreasedfrom17.6% in 2008to 23.1% in 2018(Fig.1). Theadjusted 30-day survival increasedmarkedlybothamongpatientswithashockableanda non-shockablerhythm,from53.7%in2008to64.9%in2018forshockable rhythm,andfrom14.2%in2008to22.0%in2018fornon-shockable rhythm(Fig.2).Also,theadjusted30-daysurvivalinbothacademic and in non-academichospitals increased (Fig.3). Theincreased adjusted30-daysurvivalappearedtobemoremarkedinyounger Fig.1_–Adjustedtrendsoftheproportionofpatientswho

werealiveat30days,distributedbymonitoringlevelof thewards.

*Unfilledsymbolsdepictunadjustednumbers.

Fig.2–Adjustedtrendsoftheproportionofpatientswho werealiveat30days,distributedbyshockableand non-shockablerhythms.

Fig.3–Adjustedtrendsoftheproportionofpatientswho werealiveat30days,inrelationtothetypeofhospital; academicandnon-academic.

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patientsthanintheelderly,andamongpatients>85yearsofage,the adjusted30-daysurvivaldidnotchangeatall(Fig.4).

Finally,notincludedintheoriginalaimandthuspresentedas supplementarydata,inafollow-upupto10years,itwasdemonstrated that among patients suffering an IHCA, the long term survival prognosisispoorregardlessofcalendaryearofcardiacarrestand evenworseforpatientssufferingthearrestonnon-monitoringwards (SupplementaryFig.1).

Proportionofpatientsfoundinshockablerhythms

Theproportionofpatientsfoundinshockablerhythmsdecreased overallfrom31.6%in2008to23.6%in2018.Amongpatientssuffering anIHCAonmonitoringwards, theproportionofpatientsfoundin shockablerhythmsdecreased from42.5% to 35.8%,and among patientsufferinganIHCAonnon-monitoringwards,theproportion decreasedfrom20.1%to12.9%(Fig.5).

Patientcharacteristicsandvariousaspectsofresuscitation

Whenlookingatchangesinrelationtomonitoringleveloftheward, twochanges of presumed clinicalrelevance (standardised mean

difference(SMD)moreorequalto0.1)appeared;(1)therewasan increaseintheprevioushistoryofrespiratoryinsufficiencyon non-monitoringwardsovertime.(2)Therewasalsoadecreaseintheuse ofbufferingagentsonbothtypesofwards(SupplementaryTable1). Whenlookingatchangesinrelationtothefirstrecordedrhythm,we foundthattheproportionofpatientsfoundinshockablerhythmsand defibrillatedbeforethearrivalofthecardiacarrestteam,increased over time from 71.0% to 80.9%. Furthermore, the proportion of patientswith aprevioushistoryofheart failuredecreasedamong patients foundinashockablerhythm.Incontrast,patientswitha previoushistoryofrespiratoryinsufficiencyincreasedamongpatients foundinanon-shockablerhythm.Finally,theuseofbufferingagents decreasedovertime,independentoftheinitialrhythm (Supplemen-taryTable2).

Discussion

Inthisstudyofallin-hospitalcardiacarrestsintheSwedishRegistryof CardiopulmonaryResuscitationbetween2008and2018,themost crucial finding was the increased30-day survival in all facilities, regardless ofmonitoring levelof theward andtheinitial rhythm, despite shockable rhythms decreasing over time. An increased proportionofpatientsdefibrillatedbeforethearrivalofthecardiac arrestteam,whenfoundinashockablerhythm,mayhavecontributed totheimprovedsurvivalrates.Presumably,othercausesareinvolved aswell.

Theentirestudygroupwascharacterisedbyarelativelyhighage (meanage>70yearsofage)attheoccurrenceofcardiacarrest,even though_“donotattemptresuscitation_”ordershavebeenreportedtobe relatively high among the elderly.9 In agreement with previous studies,10,11wefoundaninverserelationshipbetweensurvivaland age. Several studieshave indicateda clearassociation between increasing age and poor outcomeand vice versa.11,12 _However,

recentresearchsuggeststhatbiologicalratherthanchronologicalage mightbeabetterpredictorofmortality.2,13

Ourstudyisnotthefirsttoreportonanincreaseinsurvivalafter IHCA in a countrywide perspective. From the Get With The Guidelines-Resuscitation(GWTG-R)registry,itwasrecentlyreported thatthesurvivalafterIHCAhadincreasedovertimeina17-year perspective.14_Similarly_to_our_findings,_their_results_suggested_a_more

markedincreaseinsurvivalinyoungerpatients.

It is only possible to hypothesise about the mechanisms accountableforanincreaseinthe30-daysurvivaltrend.Apossible explanationcouldbeachangeinthepatientsco-morbidity.However, theonlyrelevantchangesinco-morbiditywasadecreaseinheart failureamongthepatientsfoundinashockablerhythm,aswellasan increase in thehistory ofrespiratory insufficiencyamongpatients foundin anon-shockablerhythmorsufferinganIHCAona non-monitoringward.Although,inpreviousstudies,ahistoryofrespiratory insufficiencyhasbeenstronglyassociatedwithreducedsurvivalafter IHCA.15,16Conversely,thechangeinco-morbidityobservedinour studywould,atleastinoneaspect,tendtodecrease ratherthan increasethesurvivalrateafterIHCA.Thedecreaseinheartfailure overtimewould,ontheotherhand,tendtoimproveoutcome.

ThedelayfromcollapsetothestartofCPRandtodefibrillationis bothcrucialandinverselyproportionaltothechanceofsurvivalin cardiacarrest.17,18Wedidnotfindanymarkedchangesovertime, neitherintheproportionofpatientsreceivingCPRbeforethearrivalof thecardiacarrestteamnorinthedelayfromcollapsetostartofCPR. Fig.4–Adjustedtrendsoftheproportionofpatientswho

werealiveat30days,inrelationtoage.

Fig.5–Trendsoftheproportionofpatientswithaninitial shockablerhythmdistributedbymonitoringlevelofthe wards.

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However,theproportionofpatientsfoundinashockablerhythmand defibrillatedbeforethearrivalofthecardiacarrestteamincreased, whichmayhavecontributedtotheincreasedsurvival.Webelievethe bestexplanationforthisimprovementisgreaterawarenessandCPR trainingofthestaff.19However,thedelayfromcollapsetodefibrillation didnotchangeovertime.

Onenotableandtosomeextentpuzzlingobservationwasthe markeddecreaseinshockablerhythmsintheeventofcardiacarrest, primarilyonnon-monitoringwards.Asimilarfindinghasbeenreported inasingletertiaryhospital,3andithasmoreoverbeenrepeatedly observedamongpatientswithOHCA.20Theunderlyingmechanism remains unexplained, but it is possible to speculate about an association with a decreased cardiacaetiology in cardiac arrest due to a number of factors, including improved cardiovascular pharmacologicaltreatment,theuseofearlyrevascularisationinacute myocardial infarction and more frequent implantation of internal cardioverterdefibrillators.20

Thesurvivalofpatientsfoundinashockablerhythmwashigh, morethanhalfsurvivedtooneyear(56.8%)inthelatertimeperiod, andiftheeventoccurredonawardwithmonitoringfacilities,afull 64.2%survivedtooneyear.Eveniftheone-yearsurvivalratefor patientssufferinganon-shockablecardiacarrestwassubstantially lower(16.6%),thechanceofsurvivalincreasedconsiderablyduring thestudyperiod.Inthiscontext,itshould berecognised thatthe prognosis after a cardiac arrest with a non-shockable rhythm is significantlyworse,aspreviouslystated.2,21

Taking other results into consideration, we presume that the improved 30-day survival after IHCA could be explained by the generally better-trained staff, resulting in a higher proportion of patientsdefibrillatedbeforethearrivalofthecardiacarrestteam. EnhancedqualityofCPRandamorepositiveattitudetoCPRamong healthcareprofessionalsmaybeothercontributoryfactors.22Another possibilityisanincreasedselectionofthepopulationthrough“donot attempt resuscitation” orders, excluding an increasing numberof elderly individuals and patients with multiple disorders, from resuscitation. Finally, a more assertive approach to finding and treating reversible causes of the cardiac arrest throughinvasive vascularprocedures,besidesmorerefinedpost-arrestcriticalcare, mightalsobepartofthereason.

Thereported30-daysurvivalin Sweden maybe regardedas relativelyhigh.Therearenotmanynationalreportsregardingsurvival afterIHCAinEurope.AreportfromtheUnitedKingdomfoundan overallunadjustedsurvivaltohospitaldischargeof18.4%23anda recentreportfromtheDanishregistryofIHCAreportedanunadjusted 30-daysurvivalof27.8%.24

Inordertobroadentheperspective,wefinallypresentlongterm survivalof our studygroups. There appear to be relatively even declinesinlongtermsurvival,regardlessofmonitoringlevelofthe ward.Suchafindingshouldberelatedtotherelativelyhighageofthe patientsatthetimeofcardiacarrest.

Studystrengthsandlimitations

Thestudywaspopulation-basedwithwell-definedinclusion/exclusion criteriaandconsiderablesamplesize.Basically,alladult patients sufferinganIHCAinwhomresuscitationwasattemptedinthemajority ofhospitalsinSweden,duringaperiodof11years,wereprospectively andretrospectivelyrecorded. Treatmentinterventionsandsurvival fromIHCAhaveonlybeendescribedfromanationalperspectiveina

fewcountriesinEurope.23,24_All_the_variables_included_in_the_analyses

werestrictlydefinedapriori.

Inspiteofthis,limitationtoasinglecountrymakesextrapolationto otherhealthcaresystemsandhospitalsoutsideSwedendifficult.As withallregistrystudies,therewasmissinginformation.Finally,there areuncertaintiesregardingthetimeintervalsthatweremeasured.

Conclusions

Inan11-yearperspective,resuscitationinin-hospitalcardiacarrestin Swedenwascharacterisedbyanoverallincreaseintheadjusted 30-daysurvival,bothonmonitoringandnon-monitoringwards,despitea decreaseinshockablerhythms,particularlyonnon-monitoringwards. Anincreasedproportion,amongthepatientsfoundinashockable rhythm,whoweredefibrillatedbeforethearrivalofacardiacarrest teammayhavecontributedtothefinding.

Authors

’

contributions

Allauthorshavedirectlyparticipatedintheplanningand implementa-tionofthestudy,andintheanalysesandinterpretationofdata.All authorshavereadandapprovedthefinalversionofthesubmitted manuscript.Therearenorelatedmanuscriptsorabstracts,published orunpublished,byanyoftheauthorsofthispaper.

Conflicts

of

interest

Noneoftheauthorshasanyconflictofinteresttodeclare.

Acknowledgements

ThestudywassupportedbytheSwedishstateundertheagreement betweentheSwedishgovernmentandthecountycouncil(theALF agreement;ALFGBG716901,ALFGBG74200),theSwedishHeart andLungFoundation,theSwedishResearchCouncil(2019-02019) andtheGothenburgMedicalSociety.

Appendix

A. Supplementary

data

Supplementary materialrelatedtothisarticlecanbefound,inthe onlineversion,atdoi:https://doi.org/10.1016/j.resuscitation.2020.10. 015.

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