體外膜肺氧合治療重度急性呼吸窘迫綜合征

CONTENTS1.Background2.Methods3.Results4.Discussion5.ConclusionBackground1.ARDSisassociatedwithhighmortalitydespitetheuseoflow--volume,low--pressureventilationstrategiesthatareaimedatreducingventilator--inducedlunginjury.2.ThemostsevereformsofARDSmaybeassociatedwithmortalityexceeding60%.3.Inthesesituations,somecenterswillusevenovenousextracorporealmembraneoxygenation(ECMO),andpatientswhoreceivedECMOtherapyappearedtobenefit.4.WedesignedtheECMOtoRescueLungInjuryinSevereARDS(EOLIA)trialtodeterminetheeffectofearlyinitiationofECMOinpatientswiththemostsevereformsofARDS.Methods

Patientswereeligibleforenrollment1.IftheirconditionfulfilledtheAmerican–EuropeanConsensusConferencedefinitionforARDS.2.Iftheyhadundergoneendotrachealintubationandhadbeenreceivingventilationforlessthan7days.3.iftheymetdisease-severitycriteria(includingPao2:Fio2of<50mmHgfor>3hours,aPao2:Fio2of<80mmHgfor>6hours,orpHof<7.25withPaco2of≥60mmHgfor>6hours,withtherespiratoryrateincreasedto35breathsperminuteandmechanical--ventilationsettingsadjustedtokeepaplateaupressureof≤32cmofwater)despiteventilatoroptimization(definedasFio2of≥0.80,atidalvolumeof6mlperkilogramofpredictedbodyweight,andPEEP≥10cmh2o).MethodsExclusioncriteria1.Anageoflessthan18years;2.Receiptofmechanicalventilationfor7daysorlonger;3.Pregnancy;4.Aweightofmorethan1kgpercentimeterofheightorabody-massindex(theweightinkilogramsdividedbythesquareoftheheightinmeters)ofmorethan45;5.Long-termchronicrespiratoryinsufficiencytreatedwithoxygentherapyornoninvasiveventilation;6.CardiacfailureresultinginvenoarterialECMO;7.Ahistoryofheparin--inducedthrombocytopenia;Methods8.Cancerwithalifeexpectancyoflessthan5years;9.AmoribundconditionoraSimplifiedAcutePhysiologyScore(SAPS--II)valueofmorethan90(onascalefrom0to163,withhigherscoresindicatinggreaterseverityofillness)onthedayofrandomization;10.Acurrentnon–drug--inducedcomaaftercardiacarrest;11.Irreversibleneurologicinjury;12.Adecisiontowithholdorwithdrawlife--sustainingtherapies;13.AnexpecteddifficultyinobtainingvascularaccessforECMOinthefemoralorjugularvein;orasituationinwhichtheECMOdevicewasnotimmediatelyavailable.

SAPS-Ⅱ評分SAPS-Ⅱ各變量的定義

MethodsTrialProceduresRandomizationwasstratifiedaccordingtocenterandthedurationofventilationbeforerandomization(<72hoursvs≥72hours).PatientsassignedtotheECMOgroupunderwentpercutaneousvenovenouscannulation.Anticoagulationwasachievedwithunfractionatedheparinthatwasadjustedtoatargetactivatedpartial--thromboplastintimeof40to55secondsoranti--Xaactivitybetween0.2and0.3IUpermilliliter.PatientsinthecontrolgroupreceivedventilatorytreatmentaccordingtotheincreasedrecruitmentstrategyfromtheExpresstrial.MethodsNeuromuscularblockingagentsandprolongedperiodsofpronepositioningwerestronglyencouraged.Recruitmentmaneuvers,inhalednitricoxide,inhaledprostacyclin,orintravenousalmitrinecouldbeusedwhenoxygenationobjectiveswerenotmet.CrossovertoECMOforpatientsinthecontrolgroupwasallowediftheyhadrefractoryhypoxemia(oxygensaturation[Sao2]of<80%for>6hours,despitetheuseofavailableandfeasibleadjunctivetherapies)andifthetreatingphysicianthoughtthatthepatienthadnoirreversiblemultiorganfailureandthatECMOmightchangetheoutcome.MethodsEndPoints：Theprimaryendpointwasmortalityat60days.Thekeysecondaryendpointwastreatmentfailure,whichwasdefinedascrossovertoECMOordeathinpatientsinthecontrolgroupandasdeathinpatientsintheECMOgroup.Otherendpointsincludedmortalityatothertimepoints,thetimetodeathuntilday60,andaper-treatmentanalysisinwhichmortalitywascomparedamongpatientswhoreceivedECMOandthosewhodidnot.Safetyendpointsincludedtheratesofpneumothorax,stroke,infectionatthesiteofECMOcannulainsertion,cannulathrombosis,ECMOcircuitchange,intravascularhemolysis,ventilator-associatedpneumonia,severehemorrhagiccomplications,andred-celltransfusion.MethodsStatisticalAnalysisTheexpectedmortalityat60dayswas60%inthegroupreceivingconventionalventilationandwasestimatedat40%amongthosereceivingearlyECMOsupport.Wecalculatedthat,inorderforthetrialtohave80%power,atanalphalevelof5%andwithagroup--sequentialanalysisoccurringaftertherandomizationofevery60participants,themaximumsamplewouldneedtobe331participants.Thecharacteristicsofthepatientsatbaselinearereportedaspercentagesforcategoricalvariablesandasmeans(withstandarddeviations)ormedians(withinterquartileranges)forcontinuousvariables,asappropriate.MethodsPrimaryanalyseswereconductedaccordingtotheintention-to-treatprincipleanddidnotuseastratifiedteststatistic.CategoricalvariableswerecomparedwithchisquareorFisher’sexacttests,andcontinuousvariableswerecomparedwithStudent’st-testoraWilcoxontest,asappropriate.Kaplan–Meiersurvivalcurvesuntil60daysafterrandomizationwerecomparedwithalog-ranktest.AplannedsensitivityanalysiswasperformedwiththeuseofaCoxregressionmodeltoadjustforprespecifiedbaselinevariables:causeofARDS,coexistingconditions,ageofthepatient,durationofmechanicalventilationbeforerandomization,diseaseseverityatinclusion,andcenter.ResultsTrialTreatmentOfthe121patientsintheECMOgroupwhoreceivedECMOatameanof3.3±2.8hoursafterrandomization,insertionofthecannulawasperformedinthefemoralandjugularveinsin116(96%).Atotalof48of124patients(39%)wereretrievedfromnon--ECMOcentersbythemobileECMOrescueteam.ECMOsupportlastedameanof15±13days.Discussion

InthisrandomizedtrialinvolvingpatientswithverysevereARDS,earlyapplicationofECMOwasnotassociatedwithmortalityat60days(primaryendpoint)thatwassignificantlylowerthanthatinthecontrolgroup.AlthoughtheuseofECMOforsevererespiratoryfailurehasincreasedsubstantiallyoverthepastdecade,itsuseremainscontroversial.Theresultsofthemostrecenttrialwereencouraging,butnotallpatientsintheECMOgroupreceivedECMO,andtheuseofmechanicalventilationinthecontrolgrouplackedstandardization.Discussion4.Inthepresenttrial,98%ofthepatientsintheECMOgroupreceivedECMOandweretransportedduringreceiptofECMOtothereferralcenterifneeded.Moreover,90%ofthepatientsinthecontrolgroupunderwentprolongedpronepositioningandallofthemreceivedneuromuscularblockingagents.5.Despitetheuseofthesestrategies,whichhavebeenshowntoimproveoutcomes,28%ofthepatientsinthecontrolgroupinourtrialcrossedovertoECMOforrefractoryhypoxemia.ThiscrossoverratemakesitdifficulttodrawdefinitiveconclusionsregardingtheusefulnessofECMOforsevereformsofARDS.Discussion

Limitations1.Itwasstoppedperpro