Clinical paper
Cut-off values of serum potassium and core temperature at hospital admission for
extracorporeal rewarming of avalanche victims in cardiac arrest: A retrospective multi-centre study
Hermann Brugger
a,b,c,*, Pierre Bouzat
d, Mathieu Pasquier
c,e, Peter Mair
f,
Julia Fieler
c,g,h, Tomasz Darocha
i, Marc Blancher
c,j,k, Matthieu de Riedmatten
l, Markus Falk
a, Peter Paal
c,m, Giacomo Strapazzon
a,c, Ken Zafren
c,n,
Monika Brodmann Maeder
a,oaInstituteofMountainEmergencyMedicine,EURACresearch,Drususallee1,39100Bolzano,Italy
bMedicalUniversityInnsbruck,Austria
cInternationalCommissionforMountainEmergencyMedicineICARMEDCOM
dDepartmentofAnaesthesiologyandCriticalCare,GrenobleAlpsTraumaCenter,UniversityHospitalofGrenoble-Alpes,38043GrenobleCedex 09,France
eEmergencyService,LausanneUniversityHospitalCenter,BH09,CHUV,CH-1011Lausanne,Switzerland
fDepartmentofAnaesthesiologyandCriticalCareMedicine,MedicalUniversityInnsbruck,Anichstraße35,6020Innsbruck,Austria
gDivisionofSurgicalMedicineandIntensiveCare,UniversityhospitalofNorthNorway,Tromsø,Norway
hAnaesthesiaandcriticalcareresearchgroup,TheArticUniversityofNorway,9037Tromsø,Norway
iDepartmentofAnaesthesiologyandIntensiveCare,MedicalUniversityofSilesia,Medykow14,40-752Katowice,Poland
jDepartmentofEmergencyMedicine,UniversityHospitalofGrenoble-Alpes,France
kFrenchMountainRescueAssociationANMSM,38043GrenobleCedex09,France
lDepartmentofEmergencyMedicine,SionHospital,Sion,Switzerland
mDepartmentofAnaesthesiologyandIntensiveCare,HospitallersBrothersHospital,ParacelsusMedicalUniversity,Kajetanerplatz1,5020 Salzburg,Austria
nDepartmentofEmergencyMedicine,StanfordUniversitySchoolofMedicine,Stanford,California,USA
oDepartmentofEmergencyMedicine,Inselspital,BernUniversityHospital,UniversityofBern,Freiburgstrasse16C,3010Bern,Switzerland
* Correspondingauthorat:InstituteofMountainEmergencyMedicine,EURACresearch,VialeDruso1,39100Bolzano,Italy.
E-mailaddresses:[email protected](H.Brugger),[email protected](P.Bouzat),[email protected](M.Pasquier), [email protected](P.Mair),[email protected](J.Fieler),[email protected](T.Darocha),[email protected](M.Blancher), [email protected](M.deRiedmatten),[email protected](M.Falk),[email protected](P.Paal),[email protected] (G.Strapazzon),[email protected](K.Zafren),[email protected](M.BrodmannMaeder).
https://doi.org/10.1016/j.resuscitation.2019.04.025
Received4October2018;Receivedinrevisedform19March2019;Accepted8April2019
0300-9572/©2019TheAuthors.PublishedbyElsevierB.V.ThisisanopenaccessarticleundertheCCBY-NC-NDlicense(http://creativecommons.org/
licenses/by-nc-nd/4.0/).ThisisanopenaccessarticleundertheCCBY-NC-NDlicense(http://creativecommons.org/licenses/by-nc-nd/4.0/).
Availableonlineatwww.sciencedirect.com
Resuscitation
j o urna lh ome p a ge :w ww . e l se v i e r . com / l oca t e / r e sus ci t a ti o n
Abstract
Aim:Evidenceofexistingguidelinesfortheon-sitetriageofavalanchevictimsislimitedandadherencesuboptimal.Thisstudyattemptedtofindreliable cut-offvaluesfortheidentificationofhypothermicavalanchevictimswithreversibleout-of-hospitalcardiacarrest(OHCA)athospitaladmission.This mayenablehospitalstoallocateextracorporeallifesupport(ECLS)resourcesmoreappropriatelywhileincreasingtheproportionofsurvivorsamong rewarmedvictims.
Methods:AllavalanchevictimswithOHCAadmittedtosevencentresinEuropecapableofECLSfrom1995to2016wereincluded.Optimalcut-off values,forparametersidentifiedbylogisticregression,weredeterminedbymeansofbootstrappingandexactbinomialdistributionandservedto calculatesensitivity,rateofovertriage,positiveandnegativepredictivevalues,andreceiveroperatingcurves.
Results:Intotal,103avalanchevictimswithOHCAwereincluded.Ofthe103patients61(58%)wererewarmedbyECLS.Six(10%)oftherewarmed patientssurvivedwhilst55(90%)died.Weobtainedoptimalcut-offvaluesof7mmol/Lforserumpotassiumand30Cforcoretemperature.
Conclusion:Forin-hospitaltriageofavalanchevictimsadmittedwithOHCA,serumpotassiumaccuratelypredictssurvival.Thecombinationofthecut- offs7mmol/Lforserumpotassiumand30Cforcoretemperatureachievedthelowestovertriagerate(47%)andthehighestpositivepredictivevalue (19%),withasensitivityof100%forsurvivors.Thepresenceofvitalsignsatextricationisstronglyassociatedwithsurvival.Forfurtheroptimisationofin- hospitaltriage,largerdatasetsareneededtoincludeadditionalparameters.
Keywords:Avalanche,Out-of-hospitalcardiacarrest,Extracorporeallifesupport,Hypothermia,Serumpotassium
Introduction
Between1983and2015about165avalanchedeathswererecorded peryearinEuropeandinNorth-America.1Survivalanalysessuggest thatmostcompletelyburiedavalanchevictimsdiebyasphyxiation between 15 and 35min after burial.2,3 Special searchstrategies, electronicdevices,4andshovellingtechniques,mayenableuninjured companionstoextricatevictimsbeforeasphyxiabecomesirrevers- ible.Thesemeasures,usedimmediatelyafteranavalanche,aremore effectivethaneffortsbyorganisedrescueteams.5Avalanchevictims whoarefoundincardiacarrestduringtheearlyburialphaseandwho receive cardiopulmonary resuscitation are at risk of permanent neurologicaldamage.6
Unlike asphyxia, hypothermiadevelops afterlongburial if the completely buried avalanche victim is able to breathe.2,7 When hypoxiahasnotprecededhypothermia,patientspresentingwithvital signsshouldberewarmedwithminimallyinvasivemethods8,9and patientsincardiacarrestwithextracorporeallifesupport(ECLS).10 These avalanche victims may recover without neurological sequelae.11
Whenavalanchevictimspresentwithcardiacarrestathospital admission,itisdifficulttodeterminethecauseofcardiacarrest.Most ofthemarealreadydeadfromasphyxia,butafewavalanchevictims may survive without neurological damage if rewarmed properly.
Clinicalandlaboratoryparameterscanhelptoidentifythosevictimsat hospitaladmissionwhomaybenefitfromECLSrewarming.
Durationofburial,patencyoftheairway,coretemperatureatthe timeofextricationandserumpotassiumathospitaladmissionhave beenidentifiedasprognosticmarkersforsurvival.12–14Recommen- dationsforon-sitetriageof avalanchevictimswith out-of-hospital cardiacarrest (OHCA)have beendeveloped since 1996to help determinewhethercardiacarrestinanavalanchevictimisdueto asphyxiaortohypothermia.1,2,7,15–17
Until2015,acut-offvalueof12mmol/Lforserumpotassiumand coretemperatureof32CwererecommendedbyboththeEuropean ResuscitationCouncil(ERC)andAmericanHeartAssociation(AHA).
The most recent algorithm for the pre-hospital management of avalanchevictimswasproposedin2015bytheERCwithacut-off level8mmol/Lforserumpotassiumand30Cforcoretemperatureat extrication.7However,allrecommendationswerebasedonexpert
consensusandcaseserieswith,admittedly,lowlevelsofevidence andhavenotpreviouslybeenvalidatedusingalargedataset.
Theaimofthisstudywastoidentifyoptimalcut-offvaluesofserum potassium and core temperature forin-hospital triage ofarrested avalanche victimsbyusingcollecteddata fromhospitalsthat are capable of ECLS. We hypothesised that it would be possible to establish optimal cut-off values with a maximum rate of 5%
undertriage(inneedoftreatment,butnottreated)and50%overtriage (notreatmentindicated,buttreated).18Thismayimprovetheabilityto identify hypothermic avalanche victims with reversible OHCA, enabling hospitalstoallocateECLSresources moreappropriately whileincreasingsurvivalrates.
Methods
Thiswasaretrospective multi-centrestudy.Firstwe performeda literaturesearchandinquiryamongall34membercountriesofthe InternationalCommissionofMountainEmergencyMedicine(ICAR MEDCOM)toidentifyhospitalsthatarecapableofECLSandhave admittedavalanchevictimswithOHCA.Thesecentreswereinvited andagreedtoparticipateinthestudy.
Data
We included all avalanche victims with OHCA, independent of rewarming,whowereadmittedtothefollowinghospitalscapableof ECLS,fromJanuary1,1995toDecember31,2016(21years):Bern (Switzerland),Grenoble(France),Innsbruck(Austria),Krakow(Po- land), Tromsø (Norway), Lausanne and Sion (Switzerland). We excludedavalanchevictimswhowerenotincardiacarrestathospital admission.Approvalbylocalinstitutionalreviewboardswasprovided bytheparticipatinghospitals.Noinformedconsentwasrequired.Data collection followed the Utstein Style for studies of patients with OHCA.19 All data were collected at the participating hospitals, transmittedto,storedandanalysedatthecoordinatingentityEURAC research.
Out-of-hospital andin-hospitalpatientdata werecollectedand analysed anonymously. No identifying elements remained which couldservetoidentifypatients,inaccordancewiththeDataProtection DirectiveoftheEuropeanUnionAgencyforFundamentalRightsand
theCouncilofEuropetogetherwiththeRegistryoftheEuropeanCourt ofHumanRights.20
Thefollowingout-of-hospitaldatawerecollected:ageandsex;
durationofcompleteburial;airwaystatusatextrication;airpocket(any spacesurroundingthemouthandnose,nomatterhowsmall,witha patentairwayatextrication15);presenceofvitalsignsatextrication;
firstcardiacrhythm;coretemperature(C)andmethodofmeasure- mentatthetimeofextrication;cardiopulmonaryresuscitation(CPR) during transport; timefrom extrication tohospital admission. The followingin-hospitaldatawerecollected:firstrecordedcardiacrhythm at admission; first recorded core temperature and method of measurement on admission; first recorded serum potassium at admission(mmol/L);injuryseverityscore;rewarmingmethod;pH;
outcomeat hospital discharge (dead,alive); ifalive, neurological outcome(cerebralperformancecategory(CPC),definingCPC1–2as goodneurologicaloutcome)athospitaldischarge.
Statisticalanalysis
Toassess possiblecut-offvaluesforhospital triagewe usedthe followingdefinitions(seeTable1):overtriagerate(underestimationof the severity) is defined as the false positive rate (1-specificity) includingthosethatwouldnotbenefitfromtreatment;undertriagerate (overestimationofseverity)isdefinedasthefalsenegativerate(1- sensitivity)excludingthosethatrequiretreatment.Maximumaccept- ablevaluesforover-andundertriageratesweresetto50%and5%
respectively.21Asamplesizeof100victimswasneededtoconfirmat leastonepredictorinlogisticregressionforhospitaltriage,assuming 10%survivors,withalpha=5%and80%power.Asthisruleisrather conservative22onecanexpectthatthemostrelevantpredictorscould beidentifiedwiththeenvisagedsamplesize.Toidentifyparameters thatcontributeindependentlytosurvivalandusingonlycasesinwhich the patient was rewarmed, we performed a stepwise logistic regressiononsurvivalwithrespecttosex,age,durationofburial, coretemperature,serumpotassiumandpH.Forserumpotassium andcoretemperaturewevisuallyassessedabilitytodiscriminateby meansofreceiveroperatingcurve(ROC)analysis.Duetothelow number of survivors, standard methods cannot be used and respective cut-offs were assessed by means of non-parametric methods. Specifically, in using the observed maximum value in survivors,thepercentageoftherespectivepercentileintheoverall sample(rewarmedandnotrewarmedcases)wasobtainedandscaled upbyafactorof1.4.Forthispercentiletheupperlimitofthe95%
confidenceinterval,calculatedbymeansofbootstrappingandexact binomialdistribution,wasusedasthecut-offvalue.Adescriptionof themethodandasensitivityanalysiscanbefoundinDatainBrief.23
Usingthismethod,weestablishedsafecut-offvaluesforserum potassiumandcoretemperatureandcalculatedsensitivity,overtriage rateandpredictivevaluesusing,firstly,onlyrewarmedcases,which correspondtothetriagesettingbutmayoverestimateeffectsduetoa possible preselection of cases, and secondly, using all cases, reflectingtheworstpossiblescenario.
For logistic regression only, missing parameter values were replacedbytheirrespectiveoverallmeans.Otherwise,acasewith onlyonemissingvalueinoneparameterwouldhavebeeneliminated fromanalysis.Forfrequencies,binomialconfidenceintervalswere estimated by means of the Jeffreys method24 and comparisons betweengroupswereperformedbymeansoftheChi-Square-testor Fisher’sexacttest,asappropriate.Forcontinuousdata,andduetothe non-normalitydistributionofsomeparameters,differencesbetween groupswereassessedbymeansoftheMann-Whitney-Utestorthe Kruskal-Wallis test. All p-values were two-sided. P-values below 0.05wereconsideredtobestatisticallysignificantly.SPSS21was used forstatistical calculations andMatlab2016for Monte Carlo simulations.
Results
FromJanuary1,1995toDecember31,2016atotalof106avalanche victimswithOHCAwereadmittedtotheparticipatingcentres(Fig.1).
Three patients were excluded (two nonsurvivors with missing potassiumandcoretemperaturevaluesandonesurvivorwhowas hitbyanavalanchewhilesittinginasnowplowthatwassweptinto water).Oftheremaining103cases,61(59%)wererewarmed,whilst 42(41%)werenotrewarmed,mostlyduetohavingaserumpotassium oracoretemperatureabovetheactualcut-offsof8mmol/Land30C (n=28,67%).
Sex,ageandvaluesofout-of-hospitalvariables areshownin Table 2. The values of variables at hospital admission and rewarming methodsareshownin Table3.Therespectivevalues andneurologicaloutcomeofsurvivorsareshowninTable4.The mean ageof thesixsurvivors was 31 years(range 17–41).The mediandurationofburialforsurvivorswas120min(range45–420).
Meancore temperatureathospitaladmissionwas22.5C(range 16.9–27.8).Themeanserumpotassiumwas3.6mmol/L(range2.7– 4.8). The mean pH was 6.91 (range 6.48–7.26). In univariate analysis the parameters duration of burial (p<0.001), core temperature (p=0.002), serum potassium (p=0.004) and pH (p=0.015)werestatistically,significantlyrelatedtosurvival,whilst sex(p=0.449)andage(p=0.637)werenot.Inmultivariateanalysis logisticregressionconfirmedcoretemperature(p=0.02)aswellas serumpotassium(p=0.03)butnotdurationofburial(p=0.481)or pH(p=0.949).
Theobservedmaximumvalueforcoretemperatureinsurvivors was27.8C,correspondingtothe58thpercentileofallobservations.
This would imply an overtriage rate above 50%, so the starting percentileforthecut-offcalculationwassettothe50thpercentile (scaledupbyafactorof1.4tothe70thpercentile),and30Cwas calculatedtobethecut-offvalueforcoretemperature(29.9Cby bootstrapping and 29.8C by the binomial method). For serum potassiumtheobservedmaximumvalueinsurvivorswas4.8mmol/L, corresponding to the 19th percentile (scaled up to the 26.6th percentile).Thecalculatedcut-offvaluewas7mmol/L(6.7mmol/L bybootstrappingand6.5mmol/Lbythebinomialmethod).Sensitivity, overtriagerateandpositiveandnegativepredictivevaluesareshown Table1–Treatmentdecisionaccordingtocut-off
value.
Cut-off Treatmentneeded
(survivors)
Notreatment needed (nonsurvivors) Beloworequal
cut-off->treat
Correctlytreated(true positive=sensitivity)
Overtriage(false positive=1- specificity) Abovecut-off->
donottreat
Undertriage(false negative)
Correctlynot treated(true negative)
inTable5.Becausecut-offvalueswerechosenconservativelyfor safety,anundertriagerateof0%(sensitivityof100%forsurvivors) wasachievedforeachvariable.Whenusingonlyrewarmedcases,the useof8mmol/Lascut-offforserumpotassiumand30Cforcore
temperatureresultedinanovertriagerateof64%(95%CI50%–75%), negativepredictivevalue(NPV)of100%(95%CI88%–100%)and positivepredictivevalue(PPV)of15%(95%CI6%–28%).Theupper limitoftheovertriagerateis75%,whichissub-optimal.Usingcut-offs of7mmol/Land30Cresultedinanovertriagerateof47%(95%CI 35%–60%),NPVof100%(95%CI92%–100%)andPPVof19%(95%
CI 8%–35%). This improves PPV by 4% (absolute difference), indicating thatatleast8%ofrewarmedcaseswillsurvivewithan overtriagerateof60%withthepossibilitythatupto8%ofpatientswho werenotrewarmedmayhavebeensurvivors.Incomparison,9cases (22%)triagedtorewarmingwithcut-offs8mmol/Land30Cwillnotbe rewarmedwhenusing7mmol/Land30C(McNemarTest,p=0.004) andwhenusingallcasesPPVisslightlylowerrangingfrom7%to 35%.
Fig.2showstheserumpotassiumandcoretemperatureofeach patient;survivorsarehighlighted.Fig.3showstheROCcurvesfor serum potassium and core temperature with the optimal cut-off values.Serumpotassium isthestrongestpredictor,butforsafety reasonsthecut-offvaluewasestimatedconservatively.
Fig.1–Flowchartofstudy.
Table2–Sex,age,durationofburial,airwaystatus,presenceorabsenceofanairpocket,presenceorabsenceof vitalsignsatextrication,firstout-of-hospitalcardiacrhythmanddurationofCPR.
Parameter Rewarmed Notrewarmed
Survivors Nonsurvivors Total(x)
Survival n=6(10) n=55(90) n=61 n=42
Center(y)(p=0.029)(*1) n=6(6) n=55(53) n=61 n=42
Bern(Switzerland) 3(100) 3(5) 6
Grenoble(France) 4(15) 22(85) 26(43) 12
Innsbruck(Austria) 1(8) 11(92) 12(20) 3
Krakow(Poland) 1(100) 1(2)
LausanneandSion(Switzerland) 9(100) 9(15) 30
Tromsø(Norway) 10(100) 10(16) 10
Sex(y)(p=0.599)(*1) n=6 n=55 n=61 n=41
Female 2(15) 11(85) 13(21) 4
Male 4(8) 44(92) 48(79) 37
Age(years)(p=0.725)(*2) n=6 n=55 n=61 n=42
MeanSD 319 3414 3413 3616
Range 17–41 2–67 2–67 14–75
Durationofburial(min)(p=0.015)(*2) n=5 n=49 n=54 n=32
Median 120 50 54 48
Range 45–420 15–320 15–420 15–150
Airwaystatus(y)(p=1.000)(*1) n=6 n=42 n=48 n=23
Blocked/unknown 2(100) 2(4) 3
Patent/free 6(13) 40(87) 46(96) 20
Airpocket(y)(p=1.000)(*1) n=5 n=39 n=44 n=19
Absent 2(9) 20(91) 22(50) 15
Present 3(14) 19(86) 22(50) 4
Vitalsignsatextrication(y)(p<0.003)(*1) n=6 n=41 n=47 n=31
Absent 1(3) 34(97) 35(74) 31
Pulse/movement/respiration 5(42) 7(58) 12(26)
DurationofCPR(min)(p<0.619)(*2) n=4 n=36 n=40 n=19
Median 63 84 79 75
Range 40–372 10–300 10–300 22–235
Firstcardiacrhythm(y)(p=0.065)(*1) n=6 n=54 n=60 n=36
Asystole 2(5) 39(95) 41(68) 32
Pulselesselectricalactivity 3(27) 8(73) 11(18) 3
Pulselessventriculartachycardia 1(33) 2(67) 3(5)
Ventricularfibrillation 5(100) 5(8) 1
(y)Numberandrowpercentage(%),(*1)Chi-SquaretestorFisher'sexacttest,(*2)Kruskal-WallistestorMann-Whitney-Utest.Plus–minusvaluesare meansSD.Rangeismintomax,(x)Columnpercentages.CPR=cardiopulmonaryresuscitation.
Discussion
In this retrospective multi-centre analysis, the characteristics of 103avalanchevictimswithOHCAadmittedtohospitalscapableof ECLSwereanalysedtodeterminetheoptimalcut-offvaluesforin- hospital triage. For serum potassium, the reduction from the previously proposed cut-off level of 12mmol/L (until 2015) to 8mmol/L(from2015)canbeconfirmedandafurtherreductionto 7mmol/Lseemstobesafe.Thecombinedcut-offs7mmol/Lforserum potassium and 30C for core temperature achieved the lowest
overtriagerate(47%)andthehighestPPV(19%),withasensitivityof 100%forsurvivors.
Deathfromavalancheshasbeenattributedtoasphyxiainabout 75–90%ofcases,totraumain5–25%,andtohypothermiainonlyafew cases.2,25–27 In previously reported cases, avalanche victims in cardiac arrest who survived neurologically intact, presented with ventricularfibrillation(VF)orpulselesselectricalactivity(PEA),6,28 andrarelywithasystole29atthetimeofextrication.
Recentstudieshaveshownthatthesurvivalrateofavalanche victims with OHCAwho were admittedfor ECLS rewarming has Table3–Cardiacrhythm,coretemperature,serumpotassiumandpHathospitaladmissionandrewarmingmethod forsurvivorsandnonsurvivors.
Parameter Rewarmed Notrewarmed
Survivors Nonsurvivors Total(x)
Cardiacrhythm(y)(p=0.008)(*1) n=5 n=40 n=45 n=37
Asystole 1(3) 33(97) 34(76) 29
Pulselesselectricalactivity 1(20) 4(80) 5(11) 4
Pulselessventriculartachycardia 1(50) 1(50) 2(4)
Ventricularfibrillation 2(50) 2(50) 4(9) 4
Coretemperature(C)(p=0.012)(*2) n=6 n=53 n=59 n=37
MeanSD 22.54.2 273.0 26.63.4 28.25.7
Range 16.9–27.8 19.1–36.0 16.9–36.0 13.0–35.5
Serumpotassium(mmol/L)(p<0.001)(*2) n=6 n=53 n=59 n=35
MeanSD 3.60.9 7.53.1 7.13.2 104.2
Range 2.7–4.8 2.3–17.5 2.7–17.5 3.4–19.0
pH(p=0.062)(*2) n=6 n=48 n=54 n=27
Mean 6.910.34 6.630.27 6.70.29 6.570.16
Range 6.48–7.26 6.1–7.25 6.1–7.26 6.2–6.9
Rewarmingmethod(y)(p=0.392)(*1) n=6 n=55 n=61 N/A
CPB 1(4) 24(96) 25(41)
ECMO 4(13) 27(87) 31(51)
Other 1(20) 4(80) 5(8)
(y)Numberandrowpercentage(%),(*1)Chi-Squaretest.(*2)Mann-Whitney-Utest.Rangeismintomax.(x)Columnpercentages.Injuryseverityscoreisnot reportedasdocumentedinonlythreecases.CPB=cardiopulmonarybypass;ECMO=extracorporealmembraneoxygenation.
Table4–Sex,age,durationofburial,airwaystatus,presenceorabsenceofairpocketandvitalsignsatextrication, cardiacrhythm,coretemperature,serumpotassiumandpHathospitaladmission,rewarmingmethodand neurologicaloutcomeofsurvivors.
ID Sex Age(years) Durationofburial
(min)
Airwaystatus Airpocket Vitalsignsat extrication
20 Male 39 45 Patent Absent Non
21 Female 36 Unknown Patent Absent Pulse
25 Male 17 360 Patent Unknown Pulse
30 Male 41 420 Patent Present Respiration
63 Male 29 90 Patent Present Pulse,respiration
64 Female 25 120 Patent Present Pulse,respiration,
movement ID Cardiacrhythmatadmission Coretemperature
atadmission(C)
Serumpotassium (mmol/L)
pH Rewarming
method
Outcomeat discharge
20 Pulselessventriculartachycardia 27.8 3.30 6.78 Peritonealdialysis CPC3
21 Pulselesselectricalactivity 26.9 2.70 7.16 CPB CPC1
25 Ventricularfibrillation 21.1 3.91 7.26 ECMO CPC1
30 Asystole 22.0 2.75 7.19 ECMO CPC1
63 Pulselesselectricalactivity 20.0 4.80 6.48 ECMO CPC1
64 Ventricularfibrillation 16.9 4.30 6.60 ECMO CPC1
CPC=cerebralperformancecategory;CPB=cardiopulmonarybypass;ECMO=extracorporealmembraneoxygenation.
remainedatabout12%.28,30,31Thisissubstantiallylowerthansurvival ratesfromall-causehypothermiccardiacarrest,whichrangefrom 23to100%.32,33Thehighrateofdeathsduetoasphyxiainavalanche victimsislikelythereasonforthesubstantiallylowersurvivalrate comparedwithhypothermiccardiacarrestfromothercauses.
Theuseofserumpotassiumlevelhasbeenproposedtopredict survivalofpatientspresentingwithhypothermiccardiacarrestfrom any cause,12,13 and, specifically to predict survival of arrested avalanchevictims.2,7,14,15Hyperkalaemiaisasignofcelldeath,but the underlying pathophysiology that leads to changes in serum potassiumduringcoolingisnotfullyunderstood. Inparticular, the effectofdeleteriouscofactorssuchastraumaandasphyxiaonthe levelofserumpotassiumiscontroversial.Inasystematicreviewof theimpact of accidentalhypothermia on serum potassium,Buse et al.34 found that among 50 studies 39 (78%) showed initial decreasesofserumpotassiumlevels,attributedtoliverpoolingand intracellularshift.In11(22%)studiesserumpotassium increased
overtimeinseverehypothermia,attributedtoamembraneleakage with passive efflux of electrolytes. The authors observed that
“theirreversibilityofcardiacarrestindeephypothermiaisadmittedly difficulttoassessandevenmoresogiventhatunderlyingcauses suchasasphyxiacanbeassociated.”Itappearsthatincreasesin serum potassium depend not only on hypothermia, but also on comorbidities suchastraumaorasphyxia, duetodamageofcell membranes.
Thehighestreportedserumpotassiumlevelsinpatientswhowere successfully rewarmedwith goodneurological outcomewereina hypothermicchildwhohadaninitialpotassiumof11.8mmol/L35and in anadultwith9.0mmol/L,36 bothexposedtocoldenvironments withoutasphyxiation.Thehighestlevelinanavalanchesurvivorwas 6.4mmol/L.14Thisdifferencebetweenthehighestrecordedserum potassium levels in hypothermia from cold exposure and from avalanche burialalsosupportstheassumptionthattheprognostic valueofserumpotassiumdependsonwhetherhypothermiaisthe solecauseofcardiacarrestorwhetherthereisassociatedasphyxiaor trauma.
Since1996,severalout-of-hospitalrecommendationshavebeen developedfortheon-sitetriageofavalanchevictimspresentingwith cardiacarrest.Thepatencyoftheairway,durationofburialandcore temperature have been proposed as decisive parameters. For example, if an avalanche victim isfound after >60min burial in asystolic cardiac arrest with a completely obstructed airway, hypothermiaisunlikelytohavebeenthecauseofcardiacarrest.In thatcase,resuscitationcanbewithheldanddeathcanbedeclaredon site.Iftheairwayisnotcompletelyobstructed,potentiallyreversible hypothermiacannotbeexcludedandthepatientshouldbetrans- portedtoahospitalforECLSrewarming.1,7
After the dissemination of triage guidelines,2,15 the use of ECLSrewarmingofavalanche victimswithOHCA decreasedin somecentres,buttheadherencetotheguidelineshasremained suboptimal.Asingle-centrestudyhasshownthataconsiderable number of avalanche victims were not selected for ECLS according to the established guidelines.37 Of the investigated patientswithashortdurationofburial (35min)27% (4of15) patientswere rewarmedwithECLS, while only29% (14 of49) patients with along duration of burial (>35min) and patent or unknownairwaysreceivedCPRandweretransportedtoahospital with ECLS. The study indicates that the adherence to out-of- hospitalrecommendationscanbepoor,andinsufficienttransferof information fromthe accident site to the hospital may partially Fig. 2 – Scatter plot with border box-plots of serum
potassium(x-axisandtop)versuscoretemperature(y- axisandrightside)ofsurvivors(red)andnonsurvivors (blue)withrespectivereferencelinesatcut-offvalues (7mmol/L for serum potassium and 30C for core temperature, n=103).(For interpretation of the refer- ences to colour in this figure legend, the reader is referredtothewebversionofthisarticle.)
Table5–Sensitivity,specificity,positiveandnegativepredictivevalueswithrespective95%confidenceintervals accordingtotriagecriteria.
Criterian=103(*) Sensitivity Overtriagerate(1-specificity) Positivepredictivevalue Negativepredictivevalue
Excludefromrewarmingwhen R A R A R A R A
K>8orcoretemperature>30
6/6(100%) 67–100
35/55 (64%) 50–75
41/97(42%) 33–52
6/41(15%)
6–28 6/47(13%)
6–24
20/20(100%) 88–100
56/56(100%) 96–100 K>7 orcoretemperature>30 26/55(47%)
35–60
31/97(32%) 23–42
6/32(19%)
8–35 6/37(16%)
7–30
29/29(100%) 92–100
66/66(100%) 96–100
(*)Givenvaluesarecounts/totaland(percentages)with95%Jeffrey’sconfidenceinterval.Totalforsensitivityandovertriageratearesurvivorsandnonsurvivors, whilstpositiveandnegativepredictivevaluesarebasedoncaseswithpositiveornegativerewarmingcriteria.Rdenotesthesampleofrewarmedcases,Adenotes allcases.
explaintherespectivepooroutcomeofarrestedavalanchevictims treatedwithemergencycardiaccare.Toaddresstheseproblems, a resuscitation checklist was published in 2014 by ICAR MEDCOM.38 It is too early to drawany conclusions regarding whether this initiative will reduce the overall number of futile rewarmingattempts of avalanche victims with OHCA,as many victimsmaystillreachthehospitalwithoutout-of-hospitaldataor withoutmeetingthecriteriaforECLSrewarming.Somehospital centreshavereported afinanciallossbytheimplementationof ECLSaccordingtotheinternationalguidelines.39Itisdesirableto establish criteria for additional in-hospital triage of avalanche victimswithOHCAthatcanbeusedevenwhennoout-of-hospital dataareavailable.
Inthisstudy,wecalculatedandcomparedsensitivity,specificity andROCsforin-hospitalcut-offvalues.Duetothelownumberof survivorstheabilitytoestimatesensitivityandundertriagerateare limited,whilstovertriagerateandpredictivevaluescanbeestimated moreaccuratelybecausenonsurvivorsarealsoincluded.Ourresults showthat serum potassium athospital admission isan accurate predictorofsurvivalandthatpredictioncanbefurtherimprovedifcore temperature is also used. A potassium level of 7mmol/L and coretemperatureof30Cseemtobetheoptimalcut-offvaluesfor triageofavalanchevictimsathospitaladmission.Usingthesevalues,
therateofovertriage(falsepositiverate=1-specificity)is47%or32%
whenusingallcases(Table5).Althoughlowercut-offvalueshave beensuggested40 todecreasetheovertriage rate,usingacut-off lowerthan7mmol/Lmaybeunsafe.
TheHypothermiaOutcomePredictionafterECLS(HOPE)score hasbeenproposedforin-hospitaltriageofpatientsincardiacarrest who are hypothermic from all causes.41 In addition to serum potassium leveland core temperature athospital admission, the HOPEscoreincludesthevariablesage,sex,mechanismofcooling and duration of cardiopulmonary resuscitation. In our study the presence of vital signs at extrication was, for example, strongly associatedwithsurvival.Survivorsalsohadalowercoretemperature andlongerdurationofburialthannonsurvivors.Thismayreflectthat cardiac arrest was primarily caused by hypothermia and not by asphyxia. However, present data sets are too small to evaluate additionalout-of-hospitalparameters.
Limitations
Thisstudyisretrospectivewithalltheusuallimitations.Theoverall numberof103 includedavalanche victimsovertheobservation period of21yearsisverylow,likelydueto thefactthatnotall avalanchevictimswhoarefoundincardiacarrestaretransported to ECLS hospitals. Moreover, the incidence of avalanche accidents varies considerably between the centres. This may reflect the regional differences in the incidence of avalanche accidentsandverylikelydifferentrescuestrategies.Cut-offvalues wereestimatedusingdataonlyfromavalanchevictimswhowere admittedtoahospitalcapableofECLS.Nodatawereavailable fromavalanche victimswithOHCA whowerenotadmitted toa hospitalcapableofECLS.Thecohortisdrawnfroma21-yeartime periodbetween1995and2016.Itispossiblethatchangesinthe management of patients over time, such asadvances in post- arrest care,had animpact onthe results. Thefirst recommen- dations for the out-of-hospital triage of avalanche victims in cardiac arrest were published in 1996. Since then, selected avalanchepatientsincardiacarrestshouldhavebeenrewarmed with ECLSaccordingtothese recommendations.Inthe investi- gated periodall participatingcentreswereequippedwithECLS facilities.
Conclusion
Forin-hospitaltriageofavalanchevictimsadmittedtohospitalsin cardiacarrest,theserumpotassium accuratelypredictedsurvival.
Thecombinedcut-offs7mmol/Lforserumpotassiumand30Cfor core temperature achieved thelowest overtriage rate(47%) and thehighestPPV(19%),withasensitivityof100%forsurvivors.The presence of vital signs at the time of extrication was strongly associatedwithsurvival.Forfurtheroptimisationofin-hospitaltriage, largerdatasetsareneededtoincludeadditionalparameters.
Conflicts of interest
HBreceivesgrantsastheheadoftheInstituteofMountainEmergency MedicinefromEURACresearch,Bolzano,Italy.Noauthorhasany conflictofinteresttodisclose.
Fig.3– Receiveroperating curve(ROC) forrewarmed avalanchevictims(n=61)withrespecttoserumpotas- siumlevels(red)andcoretemperature(blackdotted).
AreasunderthecurveforserumpotassiumAUC=0.92 (95% confidence interval 0.85-0.99, p=0.001)and for coretemperatureAUC=0.80(95%confidence interval 0.60–1.00,p=0.015).Whenconsideringaserumpotassi- umlevelof7mmol/Landcoretemperatureof30Cascut- offs,rateofovertriage(Falsepositiverate=1-specifici- ty)is47%.Therespectivecut-offvaluesaremarkedby arrows, showing that the respective cut-offs were chosenconservatively,forsafetyreasons.(Forinterpre- tationofthereferencestocolourinthisfigurelegend, thereaderisreferredtothewebversionofthisarticle.)
Acknowledgements
The authors thank the Department of Innovation, Research and UniversityoftheAutonomousProvinceofBozen/Bolzanoforcovering theOpenAccesspublicationcosts.
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