prospective follow-up of EDEN randomised trial | The BMJ

Firstly, the EDEN trial primarily evaluated relatively young, well nourished, overweight patients with acute lung injury with pneumonia or non- ... Skiptomaincontent Research Oneyearoutcomesin... Oneyearoutcomesinpatientswithacutelunginjuryrandomisedtoinitialtrophicorfullenteralfeeding:prospectivefollow-upofEDENrandomisedtrial CCBYNCOpenaccess Research Oneyearoutcomesinpatientswithacutelunginjuryrandomisedtoinitialtrophicorfullenteralfeeding:prospectivefollow-upofEDENrandomisedtrial BMJ 2013; 346 doi:https://doi.org/10.1136/bmj.f1532 (Published19March2013) Citethisas:BMJ2013;346:f1532 Article Relatedcontent Metrics Responses Peerreview DaleMNeedham,associateprofessor123,VictorDDinglas,researchprogramsupervisor12,OJosephBienvenu,associateprofessor145,ElizabethColantuoni,assistantscientist16,AmyWWozniak,researchassociate16,ToddWRice,assistantprofessor7,RamonaOHopkins,professor89fortheNIHNHLBIARDSNetwork1OutcomesAfterCriticalIllnessandSurgeryGroup,JohnsHopkinsUniversity,Baltimore,MD21205,USA2DivisionofPulmonaryandCriticalCareMedicine,SchoolofMedicine,JohnsHopkinsUniversity,Baltimore,MD21205,USA3DepartmentofPhysicalMedicineandRehabilitation,SchoolofMedicine,JohnsHopkinsUniversity,Baltimore,MD21205,USA4DepartmentofPsychiatryandBehavioralSciences,SchoolofMedicine,JohnsHopkinsUniversity,Baltimore,MD21205,USA5DepartmentofMentalHealth,BloombergSchoolofPublicHealth,JohnsHopkinsUniversity,Baltimore,MD21205,USA6DepartmentofBiostatistics,BloombergSchoolofPublicHealth,JohnsHopkinsUniversity,Baltimore,MD21205,USA7DivisionofAllergy,Pulmonary,andCriticalCareMedicine,SchoolofMedicine,VanderbiltUniversity,Nashville,TN37232,USA8DepartmentofMedicine,PulmonaryandCriticalCareDivision,IntermountainMedicalCenter,Murray,UT84107,USA9PsychologyDepartmentandNeuroscienceCenter,BrighamYoungUniversity,Provo,UT84602,USACorrespondenceto:DNeedham,PulmonaryandCriticalCareMedicine,JohnsHopkinsUniversity,1830EMonumentStreet,Baltimore,MD21205,USAdale.needham{at}jhmi.eduAccepted19February2013AbstractObjectiveToevaluatetheeffectofinitiallowenergypermissiveunderfeeding(“trophicfeeding”)versusfullenergyenteralfeeding(“fullfeeding”)onphysicalfunctionandsecondaryoutcomesinpatientswithacutelunginjury.DesignProspectivelongitudinalfollow-upevaluationoftheNHLBIARDSClinicalTrialsNetwork’sEDENtrialSetting41hospitalsintheUnitedStates.Participants525patientswithacutelunginjury.InterventionsRandomisedassignmenttotrophicorfullfeedingforuptosixdays;thereafter,allpatientsstillreceivingmechanicalventilationreceivedfullfeeding.MeasurementsBlindedassessmentoftheageandsexadjustedphysicalfunctiondomainoftheSF-36instrumentat12monthsafteracutelunginjury.Secondaryoutcomemeasuresincludedsurvival;physical,psychological,andcognitivefunctioning;qualityoflife;andemploymentstatusatsixand12months.ResultsAfteracutelunginjury,patientshadsubstantialphysical,psychological,andcognitiveimpairments,reducedqualityoflife,andimpairedreturntowork.InitialtrophicversusfullfeedingdidnotaffectmeanSF-36physicalfunctionat12months(55(SD33)v55(31),P=0.54),survivalto12months(65%v63%,P=0.63),ornearlyallofthesecondaryoutcomes.ConclusionInsurvivorsofacutelunginjury,therewasnodifferenceinphysicalfunction,survival,ormultiplesecondaryoutcomesat6and12monthfollow-upafterinitialtrophicorfullenteralfeeding.TrialRegistrationNCTNo00719446IntroductionOptimalnutritionalstrategiesformechanicallyventilatedpatientsintheintensivecareunitareuncertain.Thereissomeevidenceandrecommendationstosupportbothinitialfullenergyenteralfeeding(“fullfeeding”)andlowenergypermissiveunderfeeding(“trophicfeeding”)withdifferentrisksandbenefitsdescribed.1234567TheAcuteRespiratoryDistressSyndromeClinicalTrialsNetworkoftheNationalHeart,LungandBloodInstitutepublishedalarge,multicentrerandomisedopenlabeltrialofinitialtrophiccomparedwithfullenteralfeedingforuptosixdaysinpatientswithacutelunginjury(the“EDENtrial”).8Thistrialfoundnosignificantdifferenceinshorttermoutcomes,includingmortalityanddayswithoutventilation.Becausenutritionalinterventionshavethepotentialforlongertermeffects,9andbecauselongertermoutcomesofpatientsinintensivecareunitsmightdifferfromshorttermresults,studyoutcomesalsoshouldbeassessedoveralongertimeframe.101112131415Evaluationoflongertermfunctionaloutcomesisespeciallyimportantinpatientswithacutelunginjurybecausetrophicfeedingcanexacerbateproteinlimitationsintheintensivecareunit,16andsuchmalnutritionmightunderlieimportantmuscleloss,17persistentmuscleweakness,andfunctionalimpairmentinthesepatients.1819202122Moreover,posthocdataanalysesfromapreviousphaseIIrandomisedtrialinmechanicallyventilatedpatientsinintensivecareshowedthattheyweremorelikelytobedischargedtoarehabilitationfacilitythanhomewithtrophicratherthanfullfeeding.23Weundertookaprospectivelongitudinalevaluationofpatientoutcomesatsixand12monthsafteracutelunginjuryinparticipantsfromtheEDENstudy.Weassessedpatients’physicalfunction,qualityoflife,functionalactivities,fatigue,psychologicalsymptoms,cognition,andemploymentstatusatsixand12monthsafteracutelunginjuryandevaluatedtheeffectofinitialtrophiccomparedwithfullenteralfeedingonphysicalfunctionandsecondaryoutcomemeasures.MethodsThisstudy,theARDSNetworkLongTermOutcomesStudy(ALTOS),wasdesignedtoprospectivelyfollowpatientsenrolledinseveralARDSNetworktrials,includingtheEDENtrial.Threeofthe44hospitalsincludedintheEDENstudydidnotparticipateinthisfollow-upstudy.Consentingpatientsfromthe41participatinghospitalswereeligibleforenrolmentintothisprospectivelongitudinalstudy,withfollow-upfromApril2008toApril2012.PatientsDetailsoftheEDENeligibilitycriteriaandstudyinterventionhavebeenreportedpreviously(seeappendix).8OverthefirstsixdaysoftheEDENtrial,thetrophicfeedinggroupreceived,onaverage,1672kJ/day(25%ofcaloricgoal),whilethefullfeedinggroupreceived5434kJ/day(80%ofcaloricgoal).8WeexcludedpatientsfromtheEDENtrialiftheymetanyofthefollowingcriteria,basedontheirstatusbeforeadmissiontohospitalforacutelunginjury:cognitiveimpairment(evaluatedfromthemedicalrecordandinterviewwiththepatientand/orproxy),non-Englishspeaking,homelessness,oragedunder18.Thefirst272of1000patientsenrolledinEDENweresimultaneouslyrandomisedtoaseparateblindedtrial(theOMEGAstudy)thatexaminedanutritionalsupplementcontainingomega3fattyacidsandantioxidantscomparedwithanisoenergeticisovolemiccontrolina2×2factorialdesign.24AllEDENpatientsweremanagedwithsimplifiedversionsoflungprotectiveventilation25andfluidconservativehaemodynamicmanagement26protocols,withbloodglucosecontrolaccomplishedwithinstitutionspecificprotocolsforinsulintargetingabout4-8mmol/L,withtightercontrolpermitted.8StudyproceduresTrainedresearchstaff,blindedtotreatmentallocation,telephonedpatientsthreemonthsaftertheonsetofacutelunginjurytoprovideareminderaboutthefollow-upstudyandtoobtainupdatedcontactinformationforthepatientanddesignatedproxies.Theycompletedthestudyassessmentsatsixand12months.Publishedmethodswereusedtominimiselosstofollow-up.272829303132Whenpatientscouldnotcompletetheassessmentsbytelephone,studyassessmentswerecompletedbymail(5%ofallassessments)and/orbydesignatedproxies(onlyforthefunctionalperformanceinventoryandtheemploymentsecondaryoutcomemeasures,representing9%oftheseassessments).PrimaryandsecondaryoutcomesTheprimaryoutcomewasthephysicalfunctiondomainofSF-36(version2)instrument,33adjustedforageandsex(range0-100;higherscoreisbetter).SecondaryoutcomesincludedtheageandsexadjustedSF-36mentalhealthdomain(range0-100;higherscoreisbetter)andtheSF-36physicalandmentalhealthsummaryqualityoflifenormbasedscores(range0-100;higherscoreisbetter;mean50(SD10));theEQ-5D-3L34genericqualityoflifeinstrumentwithautilityscore35(range−0.11-1.0;higherscoreisbetter)andvisualanaloguescalescore(range0-100;higherscoreisbetter);thefunctionalperformanceinventory3637overallfunctionalactivityscoreandsubscalescoresforphysicalexercise,maintaininghousehold,andbodycare(foreach,range0-3;higherscoreisbetter);functionalassessmentofchronicillnesstherapy3839fatigueintervalscalescore(range0-100;higherscoreisbetter,withscores≤68indicatingfatigue);hospitalanxietyanddepressionscale40subscalescoresforanxietyanddepressionsymptoms(foreach,range0-21;lowerscoreisbetter,withscores≥8indicatingsubstantialsymptoms);impactofeventsscale-revised41scoreforpost-traumaticstressdisordersymptoms(range0-4;lowerscoreisbetter,withscores≥1.6indicatingsubstantialsymptoms42);themini-mentalstateexaminationtelephoneversionconvertedscore43forcognition(range0-30;higherscoreisbetter,withscores≤24indicatingimpairment);andemploymentstatus(fullorparttimeworkvunemployed).StatisticalanalysesAllanalyseswerebyintentiontotreatandperformedwithSASversion9.2(SASInstitute,Cary,NC).AtwosidedP<0.05wasconsideredsignificant.Statisticalanalyseswereconductedaccordingtoanaprioriwrittenstatisticalanalysisplan.AKaplan-Meiercurvewasusedtodisplaysurvivalduringthefollow-upperiod,withacomparisonoftrophicversusfullfeedinggroupswiththelogranktest.Toevaluatechangeovertime(12vsixmonths)fortheentirestudypopulation,wecomparedcontinuousandbinaryoutcomemeasures,ignoringtreatmentassignment,usinglinearandbinomial(identitylink)regressionmodels,respectively,withgeneralisedestimatingequations44andanexchangeablecorrelationmodel.Toquantifythetreatmenteffectforthecontinuousandbinaryoutcomemeasuresassessedatsixand12months,wecreatedlinearandlogisticregressionmodels,usinggeneralisedestimatingequationswithanexchangeablecorrelationmodelandanindicatorfortreatmentgroup(trophicvfullfeeding),follow-uptime(12vsixmonths),andtheinteractionoftreatmentgroupandtime.InasecondaryanalysisfortheprimaryoutcomevariableweextendedtheabovemodeltotestforastatisticalinteractionbetweenOMEGArandomisedassignmentandEDENtreatmentgroup(trophicvfullfeeding).Weperformedadditionalsecondaryanalysesfortheprimaryoutcomevariableforaprioripatientsubgroupsatbaseline(bodymassindex(BMI)<25,25to<30,≥30),acutelunginjurysubgroup(Pa02/Fi02≤200vPa02/Fi02>200),shock(presentvabsent),andaprioristatisticalinteractions(ageandAPACHEIIIscoreascontinuousvariables).Missingdatawereexcludedfromstatisticalanalysesasonly1-6%ofeachoutcomeinstrumentevaluatedhadanymissingdata.ResultsTherewere951patientsenrolledattheEDENhospitalsparticipatinginthisstudy.Baselinepatientcharacteristicswerecomparablebetweenthetrophicandfullfeedinggroups,withameanageof52,49%women,79%white,and82%livingindependently(table1⇓).Ofthese951patients,155(16%)whosurviveduntilhospitaldischargedidnotmeeteligibilitycriteriaforthisfollow-upstudy,leaving796patientsofwhom508(64%)surviveduntil12monthsafterrandomisation(fig1⇓),withnodifferencebetweengroups(trophicvfullfeedingestimated12monthsurvival65%v63%;logrankP=0.63).Fig1Survivaluntil12monthsafterrandomisation.Curvesatanytimepointrepresentproportionofpatientssurvivinginstudyatthattime.Twoconsentingpatientswerecensoredatdateofsixmonthassessmentbecauseoflosstofollow-upthereafter.Patientsknowntobealivebutwhomissedtheir12monthfollow-upwereadministrativelycensoredatexpecteddateoftheir12monthassessmentDownloadfigure Openinnewtab Downloadpowerpoint Table1 Characteristicsofpatientswithacutelunginjuryaccordingtorandomisationtoinitialtrophicorfullenteralfeeding.Figuresaremeans(SD)unlessstatedotherwise*Viewthistable:ViewpopupViewinlinePatientoutcomesatsixand12monthsAtsixand12months,therewere525and510consentingsurvivorseligibleforfollow-up,withonly11(2%)and23(<5%)missedattherespectivefollow-uptimes(fig2⇓).Mean(SD)lengthsofstayintheintensivecareunitandinhospitalforthe525consentingpatientssurvivinguntilsixmonthfollow-upwere14(12)and22(16)days,respectively.Survivorshadsubstantiallylowerphysicalandmentalqualityoflifescorescomparedwithageandsexmatchedpopulationnorms(table2⇓),witha12monthmeanscoreonthephysicalfunctiondomainof55(SD32)comparedwiththepopulationnormof82(SD9)(P<0.001).Functionalactivitylevel,asmeasuredbytheoverallmeanscoreonthefunctionalperformanceinventory,at12monthswas2.0(SD0.7),indicating“some”difficulty.Thesephysicaloutcomesat12monthsweresignificantlyimprovedfromthesixmonthassessment(table2).Duringthe12monthfollow-up,87(18%)and57(12%)patientswereadmittedtorehabilitationandskillednursingfacilities,respectively,with267(56%)requiringeitherthesetypesofinpatientrehabilitationandnursingcareoroutpatientphysiotherapy.Substantialsymptomsofanxiety,depression,andpost-traumaticstressdisorderwerecommonat12months,affecting42%,37%,and23%ofsurvivors,respectively,withoutsignificantimprovementfromthesixmonthassessment(table2).Cognitiveimpairmentwaspresentin21%ofsurvivorsat12months,reducedfrom25%atsixmonths(P=0.06).Amongsurvivorsat12monthfollow-up,223(47%)ofthe474whoreportedontheiremploymentstatusbeforeadmissiontohospitalwereemployed;ofthesepreviouslyemployedsurvivors,107(48%)werenotworkingat12monthfollow-up,with82(77%)ofthemattributingtheirunemploymenttohealthrelatedreasons.Fig2Enrolmentandfollow-upofpatientswithacutelunginjuryaccordingtoinitialfeedingregimen.*Threeof44hospitalsinEDENtrialdidnotparticipateinfollow-upstudy,reducingoriginalsamplesizefrom1000to951;†eightknowntobealiveat12months,twootherswerecensoredforsurvivalanalysis;‡knowntobealiveat12monthsDownloadfigure Openinnewtab Downloadpowerpoint Table2 Outcomes*atsixand12monthsinpatientswithacutelunginjury.Figuresaremeans(SD)unlessstatedotherwiseViewthistable:ViewpopupViewinlineComparisonoftrophicvfullfeedingTherewasnosignificantdifferenceinthemeanageandsexadjustedSF-36physicalfunctiondomainscore(55(SD33)v55(SD31)betweentheinitialtrophicandfullfeedinggroups;meandifferenceadjustedforageandsex2(95%confidenceinterval−4to7,P=0.54).TherewasnointeractionbetweenOMEGArandomisedassignmentandtrophicversusfullfeedinggrouponthephysicalfunctiondomainscore.WiththeexceptionoftheSF-36mentalhealthmeasuresthatfavouredtrophicfeeding,therewerenosignificantdifferencesbetweentrophicandfullfeedinggroupsforallothersecondaryoutcomemeasures,includingfunctionalactivities,fatigue,psychologicalsymptoms,cognition,andemploymentstatus(table3⇓,fig3⇓).Acrosstheprimaryoutcomeandalmostallsecondaryoutcomes,thetreatmenteffectsatthesixand12monthassessmentdidnotsignificantlydiffer.Inaddition,therewerenodifferencesinsecondaryanalysesoftheapriorisubgroupsandstatisticalinteractions.Fig3Effectsize(treatmenteffect)oftreatmentinterventiononprimaryoutcome(SF-36physicalfunctiondomainadjustedforageandsex)andallsecondaryoutcomesat12months.Effectsizecalculatedastreatmenteffect(differenceinmeansorproportions,seetable3)dividedbypooledSDfromtrophicandfullfeedinggroups.6061FACIT=functionalassessmentofchronicillnesstherapy,IES-R=impactofeventsscale-revisedDownloadfigure Openinnewtab Downloadpowerpoint Table3 Outcomes*at12monthsinpatientswithacutelunginjuryaccordingtorandomisationtoinitialtrophicorfullenteralfeeding*Figuresaremeans(SD)unlessstatedotherwiseViewthistable:ViewpopupViewinlineThe12monthcumulativeincidenceofadmissiontoaphysicalrehabilitationfacilitywasgreaterinthetrophicgroup(57(23%)v30(14%),P=0.01).Therewerenosignificantdifferencesbetweenthetrophicandfullfeedinggroupsinnewresidenceinahealthcarefacilityat90days(19(7%)v11(4%),P=0.21)orinthe12monthcumulativeincidenceofadmissiontoskillednursingfacilities(29(12%)v28(13%),P=0.70)orreceiptofoutpatientphysiotherapy(121(49%)v99(46%),P=0.50).DiscussionOver12monthsoffollow-upofpatientswithacutelunginjuryfrom41hospitalsparticipatingintheEDENtrial,therewasnodifferenceinphysicalfunction(primaryoutcome),12monthsurvival,orphysical,psychologicalandcognitivefunction,oremploymentstatusatsixand12monthsbetweenthoserandomisedtoinitialtrophicversusfullenteralfeeding.Thecumulativemortalitywas36%,withsurvivorsshowingsubstantialphysical,psychologicalandcognitiveimpairments,withreducedqualityoflife,substantialneedforinstitutionalisationandphysicalrehabilitation,andimpairedreturntowork.ComparisonwithotherstudiesConsistentwiththefindingsofmainlyprevioussinglecentrestudiesofpeoplewithacutelunginjury,18224546474849thismulticentrestudyshowedimpairmentsacrossmultiplephysical,psychological,andcognitivedomains,collectivelyreferredtoas“post-intensivecaresyndrome.”50Unlikephysicaloutcomes,meanscoresforpsychologicalandcognitiveoutcomesdidnotsignificantlyimprovebetweensixand12months.Itisnotablethatpatients’baselinestatusformanyoftheseoutcomescannotbemeasuredbeforeonsetofacutelunginjury,raisingthepossibilitythatthesewerepre-existingimpairments;however,thepatientsevaluatedwererelativelyyoung,livedindependentlywithoutassistanceatbaseline,andwerefreefromcognitiveimpairmentsbeforetheillness.Moreover,theobservedimpairmentsinqualityoflifescoresatsixand12monthsweresubstantiallygreaterthanestimatedqualityoflifescoresbeforeintensivecarereportedinothergroupsofacutelunginjurysurvivors.5152Inaddition,otherlargecohortstudies,withprospectivemeasurementofstatusbeforeintensivecare,haveshownimportantnewsubsequentimpairmentsinphysical,psychological,andcognitiveoutcomes.5354555657Finally,themagnitudeandincidenceoftheseimpairmentsissupportedbythehighrateofuseofrehabilitation,newinstitutionalisation,andinabilitytoreturntoworkafteracutelunginjury.Nutritionalstrategiesinintensivecareunits,asevaluatedinthisrandomisedtrialofinitialtrophicversusfullenteralfeeding,hadnoeffectonawidespectrumofoutcomemeasuresreportedbypatients,withnodifferencesbetweengroupsforthephysicalfunctionprimaryoutcomeorfornearlyallsecondaryphysical,psychological,cognitiveandemploymentoutcomes.Thereislittleclinicalresearchinvestigatingthelongtermoutcomesofnutritionalstrategiesintheintensivecareunit;hence,limitingspecificinsightsintothepotentialreasonsforthesefindingsandemphasisingtheimportanceoffurtherresearchonthisissue.Ofnote,abouthalfofpatientsinthetrophicfeedinggroupeventuallyreceivedfullfeedingaftertheinitialsixdayperiod,aspertheEDENprotocol.Hence,perhapstheoveralldurationofdifferencesinfeedingstrategiesintheEDENpatientswasnotlongenoughtocontributetodifferencesinoutcomes.Alternatively,perhapswithinonenutritionalstrategy,potentialbenefitswerecounterbalancedbyharms,witheachmediatedbydifferentmechanismsassociatedwiththestrategy.MeandifferencesinSF-36mentalhealthscoresweresignificantbetweenthefeedinggroups,butrelativelysmallinmagnitude58andnotsupportedbysignificantdifferencesinanyofthespecificpsychologicaloutcomemeasures(suchassymptomsofanxiety,depression,andpost-traumaticstressdisorder);suchdifferencesshouldthereforebecautiouslyinterpreted.Moreover,aspreviouslyobservedinaposthocanalysisfromasimilarphaseIIrandomisedtrialofnutritioninintensivecare,23patientsinthetrophicfeedinggroupweresignificantlymorelikelythanpatientsinthefullfeedinggrouptobeadmittedtoarehabilitationfacilityover12monthfollow-up.Despitethisfinding,therewerenosignificantdifferencesinotherphysical,psychological,andcognitiveoutcomesbetweengroupsatsixand12months,andtherewerenodifferencesinnewresidenceinahealthcarefacilityat90daysorinthe12monthcumulativeincidenceofadmissiontoaskillednursingfacilityorreceiptofoutpatientphysiotherapy.Furtherexplorationofshortertermoutcomesandofmusclestrengthandperformancebasedphysicalfunctionmeasures(suchasthesixminutewalktest)couldhelpinformthisfindingastrophicfeedingmighthaveshorttermeffectsorphysiologicaleffectsnotevaluatedinthisstudy.LimitationsThestudyhasseveralstrengths,includingdetailedprospectivelongitudinalassessmentofabout500patientsrecruitedfrom41hospitals.Inaddition,atsixand12monthfollow-up,only2%and<5%ofconsentingpatientsmissedtheirvisits.Thisstudyalsohaspotentiallimitations.Firstly,theEDENtrialprimarilyevaluatedrelativelyyoung,wellnourished,overweightpatientswithacutelunginjurywithpneumoniaornon-pulmonarysepsis.Thestudy’sfindingsmightnotthereforebegeneralisabletocriticallyillpatientswhoareolder,malnourished,andwithoutinfection.Secondly,thestudyevaluatedonlypatient/proxyreportedoutcomesobtainedbyphoneormail,withoutanyperformancebasedassessments(suchasthesixminutewalktest)fromdirectevaluation.Thirdly,theopenlabeldesignoftheEDENtrialhasthepotentialtointroducebias.Inourstudy,however,thepatientoutcomesassessorsandinvestigatorswereblindedtorandomisedgroupassignment,andthewrittenstatisticalanalysisplanandstudydatawerefinalisedbeforeunblindingthetreatmentallocation.Finally,asfunctionaloutcomemeasurescanbeassessedonlyinsurvivors,mortalityafterrandomisationcouldintroducebiasinunderstandingtheeffectofarandomisedtreatmentonfunctionaloutcomes.59Thisissueisoflessimportanceinthisstudy,however,becausetherandomisedtreatmentallocationdidnotdifferentiallyaffectmortality.ConclusionThismulticentrelongitudinalstudyofoutcomesatsixand12monthsafteracutelunginjuryshowedsubstantialphysical,cognitive,andpsychologicalimpairments,withreducedqualityoflife,substantialneedforinstitutionalisationandphysicalrehabilitation,andimpairedreturntowork.Aninitialstrategyoftrophicorfullcalorieenteralfeedingdidnotaffectpatients’physicalfunctionormultiplesecondaryoutcomemeasuresatsixand12monthfollow-upafteracutelunginjury.WhatisalreadyknownonthistopicAlargemultisiterandomisedtrialshowednodifferenceinshorttermmortalityanddayswithoutventilationinpatientswithacutelunginjuryrandomisedtoinitialtrophicorfullenteralfeedinginintensivecareGivendifferencesinproteinandtotalcaloricintakebetweenthesetwofeedingstrategies,evaluationoftheeffectonpatients’longertermfunctionaloutcomesisimportantWhatthisstudyaddsIn525patientswithacutelunginjuryrecruitedfrom41UShospitals,substantialphysical,psychological,andcognitiveimpairmentswerecommonatsixand12monthfollow-upRandomisationtoinitialtrophicorfullenteralfeedingdidnotaffectphysicalfunction(primaryoutcome),survival,orpsychologicalandcognitiveoutcomesatsixand12monthfollow-upNotesCitethisas:BMJ2013;346:f1532FootnotesWethankallpatientsandtheirproxieswhoparticipatedinthestudy.WethankMelissaMcCullough,MardeeMerrill,ElizabethVayda,JonathanGellar,LauraMethvin,GitaByraiah,ShiraniRajan,ElizabethFuller,andCassieWickenwhoassistedwithdatacollection;andWilliamFlickinger,andChristopherMayhewwhoassistedwithdatamanagement.TheNationalHeart,Lung,andBloodInstituteAcuteRespiratoryDistressSyndrome(ARDS)ClinicalTrialsNetwork:UniversityofWashington,Harborview(*LHudson,SGundel,CHough,MNeff,KSims,AUngar,TWatkins);BaystateMedicalCenter(*JSteingrub,MTidswell,EBraden,LDeSouza,JGermain,CKardos,DKelley,LKozikowski,SOuellette);BaylorCollegeofMedicine(KGuntupalli,VBandi,CPope,CRoss);JohnsHopkinsUniversity(*RBrower,HFessler,DHager,PMendez-Tellez,DNeedham,KOakjones);JohnsHopkinsBayviewMedicalCenter(JSevransky,AWorkneh);UniversityofMaryland(CShanholtz,DHerr,HHowes,GNetzer,PRock,ASampaio,JTitus);UnionMemorialHospital(PSloane,TBeck,DHighfield,SKing);WashingtonHospitalCenter(BLee,NBolouri);ClevelandClinicFoundation(*HPWiedemann,RWAshton,DACulver,TFrederick,JAGuzman,JJKomaraJr,AJReddy);UniversityHospitalsofCleveland(RHejal,MAndrews,DHaney);MetroHealthMedicalCenter(AFConnors,SLasalvia,JDThornton,ELWarren);UniversityofColoradoHospital,Aurora(*MMoss,ELBurnham,LGray,JMaloney,MMealer);DenverHealthMedicalCenter(IDouglas,KOverdier,KThompson,RWolken);RoseMedicalCenter(SFrankel,JMcKeehan);SwedishMedicalCenter(MLWarner);SaintAnthony’sHospital(TBost,CHiggins,KHodgin);DukeUniversity(*NMacIntyre,LBrown,CCox,MGentile,JGovert,NKnudsen);UniversityofNorthCarolina(SCarson,LChang,SChoudhury,WHall,JLanier);VanderbiltUniversity(*APWheeler,GRBernard,MHays,SMogan,TWRice);WakeForestUniversity(*RDHite,KBender,AHarvey,PEMorris,MaryRagusky);MosesConeMemorialHospital(PWright,SGroce,JMcLean,AOverton);UniversityofVirginia(JTruwit,KEnfield,MMarshall);LDSHospitalandIntermountainMedicalCenter(*AMorris,AAustin,SBarney,SBrown,JFergeson,HGallo,TGraydon,CGrissom,EHirshberg,AJephson,NKumar,RMiller,DMurphy,JOrme,AStow,LStruck,FThomas,DWard,LWeaver);LDSHospital(PBailey,WBeninati,LBezdijan,TClemmer,SRimkus,RTanaka);McKayDeeHospital(CLawton,DHanselman);UtahValleyRegionalMedicalCenter(KSundar,WAlward,CBishop,DEckley,THill,BJensen,KLudwig,DNielsen,MPearce);UniversityofCalifornia,SanFrancisco(*MAMatthay,CCalfee,BDaniel,MEisner,OGarcia,KKordesch,KLiu,NShum,HZhou);UniversityofCalifornia,SanFrancisco,Fresno(MWPeterson,JBlaauw,KVanGundy);UniversityofCalifornia,Davis(TAlbertson,BMorrissey,EVlastelin);LouisianaStateUniversityHealthSciencesCenter-NewOrleans(*BdeBoisblanc,AAntoine,DCharbonnet,JHunt,PLauto,AMarr,GMeyaski,CRomaine,RTejedor);EarlKLongMedicalCenter,BatonRougeGeneralMedicalCenterMid-CityandBatonRougeGeneralMedicalCenterBluebonnet(SBrierre,JByrne,TJagneaux,CLeBlanc,KMoreau,CThomas);OchsnerClinicFoundation(SJain,DTaylor,LSeoane);OurLadyoftheLakeMedicalCenter(CHebert,JThompson);TulaneMedicalCenter(FSimeone,JFearon)ClinicalCoordinatingCenter:MassachusettsGeneralHospitalandHarvardMedicalSchool(*DSchoenfeld,MGuha,EHammond,NLavery,PLazar,RMorse,COldmixon,NRingwood,ESmoot,BTThompson,RWilson)NationalHeart,LungandBloodInstitute:AHarabin,SBredow,MWaclawiw,GWeinmannDataandSafetyMonitoringBoard:RGSpragg(chair),ASlutsky,MLevy,BMarkovitz,EPetkova,CWeijerProtocolReviewCommittee:JSznajder(chair),MBegg,EIsrael,JLewis,SMcClave,PParsons.*Principalinvestigator.Contributors:DMNandROHcontributedtoconceptionanddesignofthemanuscript.DMN,VDD,OJB,EC,AWW,TWR,andROHcontributedtoanalysisandinterpretationofdata.DMNdraftedthearticleandallotherauthorscriticallyreviseditforimportantintellectualcontent.Allauthorsgavefinalapprovalofthemanuscriptversiontobepublished.DMNandECareguarantors.Funding:NationalHeart,LungandBloodInstitutefundedthisfollow-upstudy(N01HR56170,R01HL091760and3R01HL091760-02S1)andtheEDENtrial(contractsHHSN268200536165CtoHHSN268200536176CandHHSN268200536179C).Allresearchersareindependentofthefundingbodies.Thefundingbodieshadnoroleinthestudydesign;inthecollection,analysisandinterpretationofdata;inthewritingofthereport;andinthedecisiontosubmitthemanuscriptforpublication.Competinginterests:AllauthorshavecompletedtheICMJEuniformdisclosureformatwww.icmje.org/coi_disclosure.pdf(availableonrequestfromthecorrespondingauthor)anddeclare:nosupportfromanyorganisationforthesubmittedwork;nofinancialrelationshipswithanyorganisationsthatmighthaveaninterestinthesubmittedworkinthepreviousthreeyears;nootherrelationshipsoractivitiesthatcouldappeartohaveinfluencedthesubmittedwork.Ethicalapproval:Thestudywasapprovedbytheinstitutionalreviewboardsateachparticipatinghospital,thetwocentresperformingoutcomeassessments,andtheEDENdataandsafetymonitoringboard;andinformedconsentwasgivenbyallpatientsortheirproxy.Datasharing:NoadditionaldataavailableThisisanopen-accessarticledistributedunderthetermsoftheCreativeCommonsAttributionNon-commercialLicense,whichpermitsuse,distribution,andreproductioninanymedium,providedtheoriginalworkisproperlycited,theuseisnoncommercialandisotherwiseincompliancewiththelicense.See:http://creativecommons.org/licenses/by-nc/2.0/andhttp://creativecommons.org/licenses/by-nc/2.0/legalcode.References↵BarrJ,HechtM,FlavinKE,KhoranaA,GouldMK.Outcomesincriticallyillpatientsbeforeandaftertheimplementationofanevidence-basednutritionalmanagementprotocol.Chest2004;125:1446-57.OpenUrlCrossRefPubMedWebofScience↵RubinsonL,DietteGB,SongX,BrowerRG,KrishnanJA.Lowcaloricintakeisassociatedwithnosocomialbloodstreaminfectionsinpatientsinthemedicalintensivecareunit.CritCareMed2004;32:350-7.OpenUrlCrossRefPubMedWebofScience↵IbrahimEH,MehringerL,PrenticeD,ShermanG,SchaiffR,FraserV,etal.Earlyversuslateenteralfeedingofmechanicallyventilatedpatients:resultsofaclinicaltrial.JPENJParenterEnteralNutr2002;26:174-81.OpenUrlAbstract/FREEFullText↵KrishnanJA,ParcePB,MartinezA,DietteGB,BrowerRG.CaloricintakeinmedicalICUpatients:consistencyofcarewithguidelinesandrelationshiptoclinicaloutcomes.Chest2003;124:297-305.OpenUrlCrossRefPubMedWebofScience↵DickersonRN,BoschertKJ,KudskKA,BrownRO.Hypocaloricenteraltubefeedingincriticallyillobesepatients.Nutrition2002;18:241-6.OpenUrlCrossRefPubMedWebofScience↵ArabiYM,HaddadSH,TamimHM,RishuAH,SakkijhaMH,KahoulSH,etal.Near-targetcaloricintakeincriticallyillmedical-surgicalpatientsisassociatedwithadverseoutcomes.JPENJParenterEnteralNutr2010;34:280-8.OpenUrlAbstract/FREEFullText↵MartinCM,DoigGS,HeylandDK,MorrisonT,SibbaldWJ.Multicentre,cluster-randomizedclinicaltrialofalgorithmsforcritical-careenteralandparenteraltherapy(ACCEPT).CMAJ2004;170:197-204.OpenUrlAbstract/FREEFullText↵RiceTW,WheelerAP,ThompsonBT,SteingrubJ,HiteRD,MossM,etal.Initialtrophicvsfullenteralfeedinginpatientswithacutelunginjury:theEDENrandomizedtrial.JAMA2012;307:795-803.OpenUrlCrossRefPubMedWebofScience↵GriffithsRD.Nutritionandsurvivalinintensivecare.MedKlinIntensivemedNotfmed1998;35:3-9.OpenUrl↵WoonFL,DunnCB,HopkinsRO.Predictingcognitivesequelaeinsurvivorsofcriticalillnesswithcognitivescreeningtests.AmJRespirCritCareMed2012;186:333-40.OpenUrlCrossRefPubMedWebofScience↵IwashynaTJ.Trajectoriesofrecoveryanddysfunctionafteracuteillness,withimplicationsforclinicaltrialdesign.AmJRespirCritCareMed2012;186:302-4.OpenUrlCrossRefPubMedWebofScience↵ZeiherBG,ArtigasA,VincentJL,DmitrienkoA,JacksonK,ThompsonBT,etal.Neutrophilelastaseinhibitioninacutelunginjury:resultsoftheSTRIVEstudy.CritCareMed2004;32:1695-702.OpenUrlCrossRefPubMedWebofScience↵CooperDJ,RosenfeldJV,MurrayL,ArabiYM,DaviesAR,D’UrsoP,etal.Decompressivecraniectomyindiffusetraumaticbraininjury.NEnglJMed2011;364:1493-502.OpenUrlCrossRefPubMedWebofScience↵SpraggRG,BernardGR,CheckleyW,CurtisJR,GajicO,GuyattG,etal.Beyondmortality:futureclinicalresearchinacutelunginjury.AmJRespirCritCareMed2010;181:1121-7.OpenUrlCrossRefPubMedWebofScience↵AngusDC,LaterrePF,HelterbrandJ,ElyEW,BallDE,GargR,etal.Theeffectofdrotrecoginalfa(activated)onlong-termsurvivalafterseveresepsis.CritCareMed2004;32:2199-206.OpenUrlPubMedWebofScience↵GriffithsRD.Nutritionforcriticallyillpatients:howmuchisenough?JAMA2012;307:845-6.OpenUrlCrossRefPubMedWebofScience↵PuthuchearyZ,RawalJ,RatnayakeG,HarridgeS,MontgomeryH,HartN.Neuromuscularblockadeandskeletalmuscleweaknessincritica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Loginorregister: Username* Password* Registerforalerts Ifyouhaveregisteredforalerts,youshoulduseyourregisteredemailaddressasyourusername CitationtoolsDownloadthisarticletocitationmanager DaleMNeedhamassociateprofessor,VictorDDinglasresearchprogramsupervisor,OJosephBienvenuassociateprofessor,ElizabethColantuoniassistantscientist,AmyWWozniakresearchassociate,ToddWRiceassistantprofessoretal NeedhamDM,DinglasVD,BienvenuOJ,ColantuoniE,WozniakAW,RiceTWetal. Oneyearoutcomesinpatientswithacutelunginjuryrandomisedtoinitialtrophicorfullenteralfeeding:prospectivefollow-upofEDENrandomisedtrial BMJ2013;346:f1532 doi:10.1136/bmj.f1532 BibTeX(win&mac)Download EndNote(tagged)Download EndNote8(xml)Download RefWorksTagged(win&mac)Download RIS(winonly)Download MedlarsDownload Help Ifyouareunabletoimportcitations,pleasecontact technicalsupportforyourproductdirectly(linksgotoexternalsites): EndNote ProCite Reference Manager RefWorks Zotero Requestpermissions AuthorcitationArticlesbyDaleMNeedham ArticlesbyVictorDDinglas ArticlesbyOJosephBienvenu ArticlesbyElizabethColantuoni ArticlesbyAmyWWozniak ArticlesbyToddWRice ArticlesbyRamonaOHopkins AddarticletoBMJPortfolio EmailtoafriendForwardthispage ThankyouforyourinterestinspreadingthewordaboutTheBMJ.NOTE:Weonlyrequestyouremailaddresssothatthepersonyouarerecommendingthepagetoknowsthatyouwantedthemtoseeit,andthatitisnotjunkmail.Wedonotcaptureanyemailaddress. 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