ARDS进展急性呼吸窘迫综合征施焕中

急性呼吸窘迫综合征广西医科大学第一附属医院呼吸内科施焕中广西医科大学第一附属医院危重症中心NEnglJMed2003;348:683-693.NEnglJMed2003;348:683-693.NEnglJMed2003;348:683-693.MethodsWeevaluated109survivorsoftheacuterespiratory

distresssyndrome3,6,and12monthsafterdischargefromthe

intensivecareunit.Ateachvisit,patientswereinterviewed

andunderwentaphysicalexamination,pulmonary-functiontesting,

asix-minute–walktest,andaquality-of-lifeevaluation.

ResultsPatientswhosurvivedtheacuterespiratorydistress

syndromewereyoung(medianage,45years)andseverelyill

(medianAcutePhysiology,Age,andChronicHealthEvaluation

score,23)andhadalongstayintheintensivecareunit(median,

25days).Patientshadlost18percentoftheirbase-linebody

weightbythetimetheyweredischargedfromtheintensivecare

unitandstatedthatmuscleweaknessandfatiguewerethereasons

fortheirfunctionallimitation.Lungvolumeandspirometric

measurementswerenormalby6months,butcarbonmonoxidediffusion

capacityremainedlowthroughoutthe12-monthfollow-up.No

patientsrequiredsupplementaloxygenat12months,but6percent

ofpatientshadarterialoxygensaturationvaluesbelow88percent

duringexercise.Themedianscoreforthephysicalroledomain

oftheMedicalOutcomesStudy36-itemShort-FormGeneralHealth

Survey(ahealth-relatedquality-of-lifemeasure)increased

from0at3monthsto25at12months(scoreinthenormalpopulation,

84).Thedistancewalkedinsixminutesincreasedfromamedian

of281mat3monthsto422mat12months;allvalueswere

lowerthanpredicted.Theabsenceofsystemiccorticosteroid

treatment,theabsenceofillnessacquiredduringtheintensive

careunitstay,andrapidresolutionoflunginjuryandmultiorgan

dysfunctionwereassociatedwithbetterfunctionalstatusduring

theone-yearfollow-up.

ConclusionsSurvivorsoftheacuterespiratorydistresssyndrome

havepersistentfunctionaldisabilityoneyearafterdischarge

fromtheintensivecareunit.Mostpatientshaveextrapulmonary

conditions,withmusclewastingandweaknessbeingmostprominent.

NEnglJMed2003;348:683-693.定义ALI/ARDS是指由心源性以外的各种肺内外致病因素导致的急性、进行性缺氧性呼吸衰竭。ALI/ARDS具有性质相同的病理生理改变，严重的ALI即被定义为ARDS。ALI/ARDS以肺微血管通透性增加、肺气容积减少、肺顺应性降低和严重肺内分流及通气/血流比例失调为病理生理特点，临床表现为不易缓解的急性进行性缺氧性呼吸衰竭，胸部X线可见肺部浸润征象。高危因素

一、直接肺损伤因素严重肺部感染、胃内容物吸入、溺水、吸入有毒气体、肺挫伤、氧中毒等。二、间接肺损伤因素脓毒症、休克、严重非胸部创伤、重症胰腺炎、大量输血、输液、体外循环、DIC等。发病机制一、血管内皮和气道上皮损伤二、中性粒细胞介导的肺损伤三、其他炎症机制细胞因子表面活性物质呼吸机引起的肺损伤其他损伤机制四、机化性肺泡炎发病机制TheNormalAlveolus(Left-HandSide)andtheInjuredAlveolusintheAcutePhaseofAcuteLungInjuryandtheAcuteRespiratoryDistressSyndrome(Right-HandSide).Intheacutephaseofthesyndrome(right-handside),thereissloughingofboththebronchialandalveolarepithelialcells,withtheformationofprotein-richhyalinemembranesonthedenudedbasementmembrane.Neutrophilsareshownadheringtotheinjuredcapillaryendotheliumandmarginatingthroughtheinterstitiumintotheairspace,whichisfilledwithprotein-richedemafluid.Intheairspace,analveloarmacrophageissecretingcytokines,interleukin-1,6,8,and10,(IL-1,6,8,and10)andtumornecrosisfactor(TNF-),whichactlocallytostimulatechemotaxisandactivateneutrophils.Macrophagesalsosecreteothercytokines,includinginterleukin-1,6,and10.Interleukin-1canalsostimulatetheproductionofextracellularmatrixbyfibroblasts.Neutrophilscanreleaseoxidants,proteases,leukotrienes,andotherproinflammatorymolecules,suchasplatelet-activatingfactor(PAF).Anumberofantiinflammatorymediatorsarealsopresentinthealveolarmilieu,includinginterleukin-1–receptorantagonist,solubletumornecrosisfactorreceptor,autoantibodiesagainstinterleukin-8,andcytokinessuchasinterleukin-10and11(notshown).Theinfluxofprotein-richedemafluidintothealveolushasledtotheinactivationofsurfactant.MIFdenotesmacrophageinhibitoryfactor.发病机机制管状髓髓磷脂脂发病机机制SurfactantProductionandRecyclingintheNormalAlveolus(PanelA)andChangesinSurfactantMetabolisminAcuteLungInjury(PanelB).Inthenormalalveolus,surfactantissynthesizedandpackagedintolamellarbodiesinthecellcytoplasm.Theselamellarbodiesthenmigratetothecellmembrane,withwhichtheyfuse,andthenarereleasedintotheair––fluidinterfacewithinthealveolus.Theysubsequentlyformanintermediatetubularstageofsurfactantcalledtubularmyelin,whichfinallyproducesthefunctionalcoatinglayer.Surfactantproteinsarealsoinvolvedinthecoatingprocess.Surfactantrecyclingoccursthroughtheendocytosisofsmallvesicles.Alterationsinsurfactantmetabolism(PanelB)mayoccuratanyofthesesteps.TheexactpathophysiologyofsurfactantmetabolisminARDShasnotbeenfullyestablished,butitislikelytoconsistofboththedestructionandthestructuralalterationofsurfactantlipidsandproteincausedbytheinflammatorymilieuoftheinjuredairspace.Inaddition,synthesisandrecyclingofsurfactantarelikelytobereducedanditsfunctionimpairedbytheaccumulationofproteinaceousmaterialwithinthealveolus.TNFdenotestumornecrosisfactor.病理2d14d14d病理4d14dPanelAshowsalung-biopsyspecimenobtainedfromapatienttwodaysaftertheonsetofthesyndromeasaresultoftheaspirationofgastriccontents.Characteristichyalinemembranesareevident(arrow),withassociatedintraalveolarredcellsandneutrophils,findingsthatareconsistentwiththepathologicaldiagnosisofdiffusealveolardamage(hematoxylinandeosin,x90).PanelsBandCshowlung-biopsyspecimensobtained14daysaftertheonsetofsepsis-associatedacutelunginjuryandtheacuterespiratorydistresssyndrome.PanelBshowsgranulationtissueinthedistalairspaceswithachronicinflammatory-cellinfiltrate(hematoxylinandeosin,x60).TrichromestaininginPanelCrevealscollagendeposition(darkblueareas)inthegranulationtissue,afindingthatisconsistentwiththedepositionofextracellularmatrixinthealveolarcompartment(x60).PanelDshowsaspecimenoflungtissuefromapatientwhodiedfourdaysaftertheonsetofacutelunginjuryandtheacuterespiratorydistresssyndrome;thereisinjurytoboththecapillaryendotheliumandthealveolarepithelium.Thereisanintravascularneutrophil(LC)inthecapillary(C).Vacuolizationandswellingoftheendothelium(EN)areapparent.Lossofalveolarepithelialcellsisalsoapparent,withtheformationofhyalinemembranesontheepithelialsideofthebasementmembrane(BM*).PanelEshowsaspecimenoflungtissueobtainedfromapatientduringthefibrosing-alveolitisphaseinwhichthereisevidenceofreepithelializationoftheepithelialbarrierwithalveolarepithelialtypeIIcells.ThearrowindicatesatypicaltypeIIcellwithmicrovilliandlamellarbodiescontainingsurfactant.TheepithelialcellimmediatelyadjacenttothiscellisintheprocessofchangingtoatypeIcell,withflattening,lossoflamellarbodies,andmicrovilli.Theinterstitiumisthickened,withdepositionofcollagen(C).临床表表现一、大大多起起病急急剧，，进展展快。。二、呼呼吸困困难、、窘迫迫，一一般氧氧疗难难以纠纠正。。三、体体格检检查：：早期期可无无明显显异常常，较较多见见呼吸吸频数数。唇唇指发发绀，，心率率增加加，肺肺部听听诊可可闻及及于罗罗音或或哮鸣鸣音，，后期期出现现湿罗罗音并并呈肺肺实变变体征征。。四、胸胸部X线表表现：：早期期可无无异常常,或或呈轻轻度间间质改改变，，表现现为纹纹理增增多、、边缘缘模糊糊，继继之出出现斑斑片状状或大大片状状阴影影，后后期两两肺可可出现现广泛泛实变变。。X线PanelAshowsananteroposteriorchestradiographfroma42-year-oldmanwiththeacuterespiratorydistresssyndromeassociatedwithgram-negativesepsiswhowasreceivingmechanicalventilation.Thepulmonary-arterywedgepressure,measuredwithapulmonary-arterycatheter,was4mmHg.Therearediffusebilateralalveolaropacitiesconsistentwiththepresenceofpulmonaryedema.PanelBshowsananteroposteriorchestradiographfroma60-year-oldmanwithacutelunginjuryandtheacuterespiratorydistresssyndromewhohadbeenreceivingmechanicalventilationforsevendays.Reticularopacitiesarepresentthroughoutbothlungfields,afindingsuggestiveofthedevelopmentoffibrosingalveolitis.PanelCshowsaCTscanofthechestobtainedduringtheacutephase.Thebilateralalveolaropacitiesaredenserinthedependent,posteriorlungzones,withsparingoftheanteriorlungfields.Thearrowsindicatethickenedinterlobularsepta,consistentwiththepresenceofpulmonaryedema.Thebilateralpleuraleffusionsareacommonfinding.PanelDshowsaCTscanofthechestobtainedduringthefibrosing-alveolitisphase.Therearereticularopacitiesanddiffuseground-glassopacitiesthroughoutbothlungfields,andalargebullaispresentintheleftanteriorhemithorax.诊断标标准一、有有发病病的高高危因因素。。二、急急性起起病，，呼吸吸频数数和（（或））呼吸吸窘迫迫。三、低低氧血血症：：ALI时时PaO2/FiO2≤300mmHg；ARDS时时PaO2/FiO2≤200mmHg。四、胸胸部X线检检查两两肺浸浸润影影响。。五、PCWP≤≤18mmHg或或临床床上能能除外外心源源性肺肺水肿肿。返符合合以上上5项项者可可诊断断为ALI或ARDS。。一、不不把是是否行行机械械通气气和行行机械械通气气的时时间纳纳入诊诊断标标准。。二、不不强调调PEEP对氧氧合的的影响响。三、为为了动动态观观察病病情变变化，，对上上机患患者应应尽量量在相相同的的通气气条件件下进进行前前后比比较。。四、PaO2/FiO2难于排除通通气功能障障碍对氧合合的影响。。在临床应应用中以PA～AO2可以更好地地反映ARDS的病病理生理特特点，从而而提高ARDS诊断断的特异性性，应用时时宜注意氧氧浓度的影影响。诊断时应注注意以下各各项五、ARDS胸片的的表现缺少少特异性，，在不同的的原发病和和不同的时时期可有不不同的表现现，可以为为间质或实实质，散在在或弥漫，，可轻可重重，但进展展迅速。。六、若能除除外左房压压高，PAWP对诊诊断ARDS并非必必须，但对对无典型胸胸片或不能能完全从临临床表现除除外左房高高压的患者者，必须有有PAWP作为诊断断条件。。七、有慢性性肺病者（（如肺间质质纤维化、、结节病等等），即使使达到ARDS的诊诊断标准也也不纳入ARDS。。诊断时应注注意以下各各项治疗一、原发病病的治疗应积极寻找找原发病灶灶并予以彻彻底治疗。。感染是导导致ARDS的常见见原因，而而且ARDS易并发发感染，所所以对于所所有的病人人都应怀疑疑感染的可可能，除非非有明确的的其他导致致ARDS的原因存存在。宜选选择广谱抗抗生素。2004-07-272004-08-122004-08-142004-08-152004-08-172004-08-182004-08-202004-08-232004-08-252004-08-272004-08-302004-08-312004-09-012004-09-032004-09-072004-09-152004-09-202004-09-232004-09-272004-09-302004-10-082004-10-172004-10-24治疗二、机机械通通气机械通通气是是ARDS最为为重要要的支支持治治疗手手段。。在掌掌握ARDS呼呼吸力力学改改变特特点的的基础础上，，合理理的使使用机机械通通气技技术对对于提提高ARDS的的抢救救成功功率具具有重重要意意义。。详见下下述。。治疗三、液液体管管理保持循环环系统较较低的前前负荷可可减少肺水水的含量量，有报报道可以以缩短上机时间间和降低低死亡率率。建议议在早期可给予予高渗晶晶体液，，此后可可给予胶体液，，同时限限制入量量，辅以以利尿剂剂，使出出入量保保持一定定水平的的负平衡衡，有条条件可监监测PAWP，，在不影影响心输输出量和和血压的的情况下下尽量降降低PAWP。。必要时时可使用用多巴胺胺和多巴巴酚丁胺胺等血管管活性药药物。CritCareMed2002;30:2175-2182.Figure1.Changeinserumtotalproteinduringthestudy,withthetreatmentperiodidentifiedbytheshadedarea.Pointsrepresentmean,witherrorbarsindicatingsem.Figure3.Changeinoxygenation,asmeasuredbythePao2/Fio2ratio(mean±±sem),withthetreatmentperiodidentifiedbytheshadedarea.*Significantwithin-groupchangefrombaseline;†timepointswithsignificantbetween-groupdifferences.Amaximumof25%ofdatapointsmaybeabsentfromcalculationsrepresentedafterday5.Figure4.Changeinthemeanarterialpressure(mmHg)/heartrate(beats/min)ratio(MAP/HRratio)frombaseline.Thetreatmentperiodisindicatedbytheshadedarea.Pointsrepresentmeanvalues,witherrorbarsdepictingsem(mean±sem)ateachtimepoint.Figure5.Kaplan-Meierplotdepictingthepercentageofpatientsrequiringmechanicalventilationduringthe30-dayfollow-upperiod.Differencesbetweengroupsarenotstatisticallysignificant.CritCareMed2002;30:2175-2182.Patients:Thirty-sevenmechanically-ventilatedpatientswithacutelunginjuryandserumtotalprotein<=5.0g/dL.Interventions:Five-dayprotocolizedregimenof25gofhumanserumalbuminevery8hrswithcontinuousinfusionfurosemide,ordualplacebo,targetedtodiuresis,weightloss,andserumtotalprotein.MeasurementsandMainResults:Measuredoutcomesincludedchangeinweight,serumtotalprotein,fluidbalance,hemodynamics,respiratorysystemcompliance,andoxygenation.Baselinecharacteristicsweresimilarbetweengroups(treatment,n=19;control,n=18),withtraumabeingthemajorcauseofacutelunginjury.Diuresisandweightlossover5days(5.3kgmoreinthetreatmentgroup,p=.04)wasaccompaniedbyimprovementsinthePao2/Fio2ratiointhetreatmentgroupwithin24hrs(from171to236,p=.02).Respiratorymechanicswereunchanged.Meanarterialpressureincreasedfrom80to88mmHg(p=.10),andheartratedecreasedfrom110to95beats/min(p=.008)overtimeinthetreatmentgroup.Nodifferenceinmortalitywasobserved,withfavorabletrendsinmeasuresofintensivecare.Conclusions:Albuminandfurosemidetherapyimprovesfluidbalance,oxygenation,andhemodynamicsinhypoproteinemicpatientswithacutelunginjury.Determiningtheeffectofthissimpletherapyoncost,outcomes,andotherpatientpopulationsrequiresfurtherstudy.NEnglJMed2004;350:2247-2256.6997patientsBackgroundItremainsuncertainwhetherthechoiceofresuscitationfluidforpatientsinintensivecareunits(ICUs)affectssurvival.Weconductedamulticenter,randomized,double-blindtrialtocomparetheeffectoffluidresuscitationwithalbuminorsalineonmortalityinaheterogeneouspopulationofpatientsintheICU.ResultsOfthe6997patientswhounderwentrandomization,3497wereassignedtoreceivealbuminand3500toreceivesaline;thetwogroupshadsimilarbaselinecharacteristics.Therewere726deathsinthealbumingroup,ascomparedwith729deathsinthesalinegroup(relativeriskofdeath,0.99;95percentconfidenceinterval,0.91to1.09;P=0.87).Theproportionofpatientswithnewsingle-organandmultiple-organfailurewassimilarinthetwogroups(P=0.85).Therewerenosignificantdifferencesbetweenthegroupsinthemean(±±SD)numbersofdaysspentintheICU(6.5±6.6inthealbumingroupand6.2±6.2inthesalinegroup,P=0.44),daysspentinthehospital(15.3±9.6and15.6±9.6,respectively;P=0.30),daysofmechanicalventilation(4.5±±6.1and4.3±5.7,respectively;P=0.74),ordaysofrenal-replacementtherapy(0.5±±±2.0,respectively;P=0.41).ConclusionsInpatientsintheICU,useofeither4percentalbuminornormalsalineforfluidresuscitationresultsinsimilaroutcomesat28days.NEnglJMed2004;350:2247-2256.治疗四、氧运输输呼吸、循环环和血液系系统的功能能状态共同同决定氧运运输量的大大小。应通通过合理的的液体疗法法、氧疗、、机械通气气、使用血血管活性药药物使氧运运输量达最最佳水平，，而不应只只着眼于某某一个脏器器的功能状状态。目前前尚无充分分证据表明明使氧运输输量达到一一个超常水水平能降低低ARDS的死亡率率。治疗五、肺外脏脏器功能的的支持和营营养支持近年年来来，，呼呼吸吸支支持持技技术术的的进进步步可可使使多多数数ARDS患患者者不不再再死死于于低低氧氧血血症症，，而而主主要要死死于于MODS。。ARDS可可使使肺肺外外脏脏器器功功能能受受损损，，而而肺肺外外脏脏器器功功能受受损损又又能能反反过过来来加加重重ARDS。。因因此此，，加强强液液体体管管理理，，尽尽早早开开始始肠肠内内营营养养，，注意意循循环环功功能能、、肾肾功功能能和和肝肝功功能能的支支持持对对于于防防止止MODS的的发发生生有有重重要意意义义。。AmJRespirCritCareMed,2004,169:638-644.Theaimofthisstudywastoevaluatetheeffectofparenteralnutritioncontainingmedium-andlong-chaintriglyceridesonthefunctionoftherespiratorysystemandtoinvestigatemechanismsinvolvedinthisprocess.Westudied13patientswithacuterespiratorydistresssyndrome(ARDS),8receivinglipidand5placebo,and6withoutARDS,receivinglipid.Bronchoalveolarlavage(BAL)wasperformedbeforeand1hourafteradministrationoflipidorplacebo.InpatientswithARDS,lipidadministrationresultedindeteriorationofoxygenation(PaO2/FIO2:from129±37to95±±42),complianceofrespiratorysystem(from39.2±±12to33.1±±9.2ml/cmH2O),andpulmonaryvascularresistance(from258±±47to321±±58dyne·s·cm-5).IntheBALfluidofthesamegroup,anincreaseintotalproteinandphospholipidconcentrations,phospholipaseactivities,platelet-activatingfactorandneutrophils,aswellasalterationsinBALlipidprofilewereobserved.NosignificantchangeswereobservedinthecontrolorintheARDS-Placebogroups.Inconclusion,thisstudyindicatesthatadministrationofmedium-andlong-chaintriglyceridesinpatientswithARDScausesalterationsinlungfunctionandhemodynamics.Inflammatorycells,possiblyactivatedbylipids,releasephospholipaseA2andplatelet-activatingfactor,enhancingedemaformation,inflammation,andsurfactantalterations.AmJRespirCritCareMed,2004,169:638-644.治疗六、其其他药药物治治疗皮质激激素在在中晚晚期应应用可可能对对防止止肺纤纤维化化有一一定作作用。。对于于脂肪肪栓塞塞综合合征和和卡氏氏肺囊囊虫肺肺炎有有预防防和治治疗作作用。。其他他抗炎炎制剂剂，如如PGE1抗内毒毒素抗抗体、、IL-1受体体抗体体、PAF受体体拮抗抗剂、、抗TNF抗体体等，，均需需进一一步研研究。。NEnglJMed2004;351:884-892.NEnglJMed2004;351:884-892.Figure1.Mean(±±SE)PaO2:FiO2ValuesintheControlGroupandtheSurfactantGroup.ThemeanPaO2:FiO2value,ameasureoftheblood-oxygenatingabilityofthelung,wassignificantlygreaterfrom4to24hoursaftertreatmentinthesurfactantgroupthaninthecontrolgroup.Figure2.NumberofVentilator-freeDaysintheControlGroupandtheSurfactantGroup.Patientswith0ventilator-freedaysincludedthosewhowereneverfreefrommechanicalventilationandthosewhodiedwithin28daysaftertreatment,regardlessoftheirneedformechanicalventilation.Therewerenosignificantdifferencesbetweenthetwogroups.Figure3.Nonpulmonary-OrganFailureduringthe28DaysafterTreatmentamongPatientswithARDSasaResultofDirectorIndirectLungInjury.DirectARDSwasdefinedasARDSduetopneumonia,aspiration,orboth.Thenumberofnonpulmonaryorgansthatfailed(withfailureofanorgandefinedasascoreof3or4SOFA)wassignificantlygreateramongpatientswithindirectARDSthanamongthosewithdirectARDS(P=0.02).NEnglJMed2004;351:884-892.MethodsIntwomulticenter,randomized,double-blindtrialsinvolving448patientswithARDSfromvariouscauses,wecomparedstandardtherapyalonewithstandardtherapyplusuptofourintratrachealdosesofarecombinantsurfactantproteinC––basedsurfactantgivenwithinaperiodof24hours.ResultsTheoverallsurvivalratewas66percent28daysaftertreatment,andthemediannumberofventilator-freedayswas0(68percentrange,0to26);therewasnosignificantdifferencebetweenthegroupsintermsofmortalityortheneedformechanicalventilation.Patientsreceivingsurfactanthadasignificantlygreaterimprovementinbloodoxygenationduringtheinitial24hoursoftreatmentthanpatientsreceivingstandardtherapy,accordingtobothunivariateandmultivariateanalyses.ConclusionsTheuseofexogenoussurfactantinaheterogeneouspopulationofpatientswithARDSdidnotimprovesurvival.Patientswhoreceivedsurfactanthadagreaterimprovementingasexchangeduringthe24-hourtreatmentperiodthanpatientswhoreceivedstandardtherapyalone,suggestingthepotentialbenefitofalongertreatmentcourse.NEnglJMed2004;351:884-892.ARDS的的机械通气气一、ARDS的呼吸吸力学特点点1．肺气容容积减少2．病变的的非均一性性3．肺顺应应性降低心脏SPARDS的的机械通气气二、呼吸机机所致肺损损伤1．肺气压压伤(barotrauma)2．肺容积积伤(volutrauma)3．肺萎陷陷伤(atelectauma)4．肺生物物伤(biotrauma)ARDS的的机械通气气三、机械通通气的策略略1．高呼气气末正压策策略2．小潮气气量策略3．长吸气气策略4．肺开放放策略ARDS的的机械通气气四、通气参参数的调节节1．吸氧浓浓度(FiO2)2．PEEP3．潮气量量4．呼吸频频率的调节节5．吸呼比比(I／E)的调节节0204060VT（L）LIPUIPNEnglJMed1998;338:347-354.NEnglJMed1998;338:347-354.BackgroundInpatientswiththeacuterespiratorydistresssyndrome,

massivealveolarcollapseandcycliclungreopeningandoverdistention

duringmechanicalventilationmayperpetuatealveolarinjury.

Wedeterminedwhetheraventilatorystrategydesignedtominimize

suchlunginjuriescouldreducenotonlypulmonarycomplications

butalsomortalityat28daysinpatientswiththeacuterespiratory

distresssyndrome.

MethodsWerandomlyassigned53patientswithearlyacuterespiratory

distresssyndrome(including28describedpreviously),allof

whomwerereceivingidenticalhemodynamicandgeneralsupport,

toconventionalorprotectivemechanicalventilation.Conventional

ventilationwasbasedonthestrategyofmaintainingthelowest

positiveend-expiratorypressure(PEEP)foracceptableoxygenation,

withatidalvolumeof12mlperkilogramofbodyweightand

normalarterialcarbondioxidelevels(35to38mmHg).Protective

ventilationinvolvedend-expiratorypressuresabovethelower

inflectionpointonthestaticpressure–volumecurve,

atidalvolumeoflessthan6mlperkilogram,drivingpressures

oflessthan20cmofwaterabovethePEEPvalue,permissive

hypercapnia,andpreferentialuseofpressure-limitedventilatory

modes.

ResultsAfter28days,11of29patients(38percent)inthe

protective-ventilationgrouphaddied,ascomparedwith17of

24(71percent)intheconventional-ventilationgroup(P<0.001).

Theratesofweaningfrommechanicalventilationwere66percent

intheprotective-ventilationgroupand29percentintheconventional-ventilation

group(P=0.005);theratesofclinicalbarotraumawere7percent

and42percent,respectively(P=0.02),despitetheuseof

higherPEEPandmeanairwaypressuresintheprotective-ventilation

group.Thedifferenceinsurvivaltohospitaldischargewas

notsignificant;13of29patients(45percent)intheprotective-ventilation

groupdiedinthehospital,ascomparedwith17of24inthe

conventional-ventilationgroup(71percent,P=0.37).

ConclusionsAscomparedwithconventionalventilation,theprotective

strategywasassociatedwithimprovedsurvivalat28days,a

higherrateofweaningfrommechanicalventilation,andalower

rateofbarotraumainpatientswiththeacuterespiratorydistress

syndrome.Protectiveventilationwasnotassociatedwithahigher

rateofsurvivaltohospitaldischarge.

NEnglJMed1998;338:347-354.NEnglJMed2000;342:1301-1308,NEnglJMed2000;342:1301-1308,BackgroundTraditionalapproachestomechanicalventilationusetidalvolumesof10to15mlperkilogramofbodyweightandmaycausestretch-inducedlunginjuryinpatientswithacutelunginjuryandtheacuterespiratorydistresssyndrome.Wethereforeconductedatrialtodeterminewhetherventilationwithlowertidalvolumeswouldimprovetheclinicaloutcomesinthesepatients.ResultsThetrialwasstoppedaftertheenrollmentof861patientsbecausemortalitywaslowerinthegrouptreatedwithlowertidalvolumesthaninthegrouptreatedwithtraditionaltidalvolumes(31.0percentvs.39.8percent,P=0.007),andthenumberofdayswithoutventilatoruseduringthefirst28daysafterrandomizationwasgreaterinthisgroup(mean[±SD],12±11vs.10±±±0.8mlperkilogramofpredictedbodyweight(P<0.001),respectively,andthemeanplateaupressureswere25±6and33±8cmofwater(P<0.001),respectively.ConclusionsInpatientswithacutelunginjuryandtheacuterespiratorydistresssyndrome,mechanicalventilationwithalowertidalvolumethanistraditionallyusedresultsindecreasedmortalityandincreasesthenumberofdayswithoutventilatoruse.N