2020年ARDS进展(急性呼吸窘迫综合征)-施焕中参考模板课件

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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1NEnglJMed2003;348:683-693.NEnglJMed2003;348:683-6932NEnglJMed2003;348:683-693.NEnglJMed2003;348:683-6933NEnglJMed2003;348:683-693.NEnglJMed2003;348:683-6934MethodsWeevaluated109survivorsoftheacuterespiratory

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.MethodsWeevaluated109survi5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。定义ALI/ARDS是指由心源性以外的各种肺6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。高危因素一、直接肺损伤因素7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发病机制一、血管内皮和气道上皮损伤8发病机制发病机制9TheNormalAlveolus(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.TheNormalAlveolus(Left-Hand10发病机制管状髓磷脂发病机制管状髓磷脂11发病机制发病机制12SurfactantProductionandRecyclingintheNormalAlveolus(PanelA)andChangesinSurfactantMetabolisminAcuteLungInjury(PanelB).Inthenormalalveolus,surfactantissynthesizedandpackagedintolamellarbodiesinthecellcytoplasm.Theselamellarbodiesthenmigratetothecellmembrane,withwhichtheyfuse,andthenarereleasedintotheair–fluidinterfacewithinthealveolus.Theysubsequentlyformanintermediatetubularstageofsurfactantcalledtubularmyelin,whichfinallyproducesthefunctionalcoatinglayer.Surfactantproteinsarealsoinvolvedinthecoatingprocess.Surfactantrecyclingoccursthroughtheendocytosisofsmallvesicles.Alterationsinsurfactantmetabolism(PanelB)mayoccuratanyofthesesteps.TheexactpathophysiologyofsurfactantmetabolisminARDShasnotbeenfullyestablished,butitislikelytoconsistofboththedestructionandthestructuralalterationofsurfactantlipidsandproteincausedbytheinflammatorymilieuoftheinjuredairspace.Inaddition,synthesisandrecyclingofsurfactantarelikelytobereducedanditsfunctionimpairedbytheaccumulationofproteinaceousmaterialwithinthealveolus.TNFdenotestumornecrosisfactor.SurfactantProductionandRecy13病理2d14d14d病理2d14d14d14病理4d14d病理4d14d15PanelAshowsalung-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).PanelAshowsalung-biopsysp16临床表现一、大多起病急剧，进展快。二、呼吸困难、窘迫，一般氧疗难以纠正。三、体格检查：早期可无明显异常，较多见呼吸频数。唇指发绀，心率增加，肺部听诊可闻及于罗音或哮鸣音，后期出现湿罗音并呈肺实变体征。四、胸部X线表现：早期可无异常,或呈轻度间质改变，表现为纹理增多、边缘模糊，继之出现斑片状或大片状阴影，后期两肺可出现广泛实变。临床表现一、大多起病急剧，进展快。17X线X线18PanelAshowsananteroposteriorchestradiographfroma42-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.PanelAshowsananteroposteri19诊断标准一、有发病的高危因素。二、急性起病，呼吸频数和（或）呼吸窘迫。三、低氧血症：ALI时PaO2/FiO2≤300mmHg；ARDS时PaO2/FiO2≤200mmHg。四、胸部X线检查两肺浸润影响。五、PCWP≤18mmHg或临床上能除外心源性肺水肿。返符合以上5项者可诊断为ALI或ARDS。诊断标准一、有发病的高危因素。20一、不把是否行机械通气和行机械通气的时间纳入诊断标准。二、不强调PEEP对氧合的影响。三、为了动态观察病情变化，对上机患者应尽量在相同的通气条件下进行前后比较。四、PaO2/FiO2难于排除通气功能障碍对氧合的影响。在临床应用中以PA～AO2可以更好地反映ARDS的病理生理特点，从而提高ARDS诊断的特异性，应用时宜注意氧浓度的影响。诊断时应注意以下各项一、不把是否行机械通气和行机械通气的时间纳入21五、ARDS胸片的表现缺少特异性，在不同的原发病和不同的时期可有不同的表现，可以为间质或实质，散在或弥漫，可轻可重，但进展迅速。六、若能除外左房压高，PAWP对诊断ARDS并非必须，但对无典型胸片或不能完全从临床表现除外左房高压的患者，必须有PAWP作为诊断条件。七、有慢性肺病者（如肺间质纤维化、结节病等），即使达到ARDS的诊断标准也不纳入ARDS。诊断时应注意以下各项五、ARDS胸片的表现缺少特异性，在不同的原22治疗一、原发病的治疗应积极寻找原发病灶并予以彻底治疗。感染是导致ARDS的常见原因，而且ARDS易并发感染，所以对于所有的病人都应怀疑感染的可能，除非有明确的其他导致ARDS的原因存在。宜选择广谱抗生素。治疗一、原发病的治疗232004-07-272004-08-122004-08-142004-08-152004-08-172004-08-182004-07-272004-08-122004-08-14242004-08-202004-08-232004-08-252004-08-272004-08-302004-08-312004-08-202004-08-232004-08-25252004-09-012004-09-032004-09-072004-09-152004-09-202004-09-232004-09-012004-09-032004-09-07262004-09-272004-09-302004-10-082004-10-172004-10-242004-09-272004-09-302004-10-0827治疗二、机械通气机械通气是ARDS最为重要的支持治疗手段。在掌握ARDS呼吸力学改变特点的基础上，合理的使用机械通气技术对于提高ARDS的抢救成功率具有重要意义。详见下述。治疗二、机械通气28治疗三、液体管理保持循环系统较低的前负荷可减少肺水的含量，有报道可以缩短上机时间和降低死亡率。建议在早期可给予高渗晶体液，此后可给予胶体液，同时限制入量，辅以利尿剂，使出入量保持一定水平的负平衡，有条件可监测PAWP，在不影响心输出量和血压的情况下尽量降低PAWP。必要时可使用多巴胺和多巴酚丁胺等血管活性药物。治疗三、液体管理29CritCareMed2002;30:2175-2182.CritCareMed2002;30:2175-230Figure1.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.Figure1.Changeinserumtota31Patients: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.Patients:Thirty-sevenmechani32NEnglJMed2004;350:2247-2256.6997patientsNEnglJMed2004;350:2247-2233BackgroundItremainsuncertainwhetherthechoiceofresuscitation

fluidforpatientsinintensivecareunits(ICUs)affectssurvival.

Weconductedamulticenter,randomized,double-blindtrialto

comparetheeffectoffluidresuscitationwithalbuminorsaline

onmortalityinaheterogeneouspopulationofpatientsinthe

ICU.

ResultsOfthe6997patientswhounderwentrandomization,3497

wereassignedtoreceivealbuminand3500toreceivesaline;

thetwogroupshadsimilarbaselinecharacteristics.Therewere

726deathsinthealbumingroup,ascomparedwith729deaths

inthesalinegroup(relativeriskofdeath,0.99;95percent

confidenceinterval,0.91to1.09;P=0.87).Theproportionof

patientswithnewsingle-organandmultiple-organfailurewas

similarinthetwogroups(P=0.85).Therewerenosignificant

differencesbetweenthegroupsinthemean(±SD)numbers

ofdaysspentintheICU(6.5±6.6inthealbumingroup

and6.2±6.2inthesalinegroup,P=0.44),daysspent

inthehospital(15.3±9.6and15.6±9.6,respectively;

P=0.30),daysofmechanicalventilation(4.5±6.1and

4.3±5.7,respectively;P=0.74),ordaysofrenal-replacement

therapy(0.5±2.3and0.4±2.0,respectively;P=0.41).

ConclusionsInpatientsintheICU,useofeither4percent

albuminornormalsalineforfluidresuscitationresultsin

similaroutcomesat28days.NEnglJMed2004;350:2247-2256.BackgroundItremainsuncertai34治疗四、氧运输呼吸、循环和血液系统的功能状态共同决定氧运输量的大小。应通过合理的液体疗法、氧疗、机械通气、使用血管活性药物使氧运输量达最佳水平，而不应只着眼于某一个脏器的功能状态。目前尚无充分证据表明使氧运输量达到一个超常水平能降低ARDS的死亡率。治疗四、氧运输35治疗五、肺外脏器功能的支持和营养支持近年来，呼吸支持技术的进步可使多数ARDS患者不再死于低氧血症，而主要死于MODS。ARDS可使肺外脏器功能受损，而肺外脏器功能受损又能反过来加重ARDS。因此，加强液体管理，尽早开始肠内营养，注意循环功能、肾功能和肝功能的支持对于防止MODS的发生有重要意义。治疗五、肺外脏器功能的支持和营养支持36AmJRespirCritCareMed,2004,169:638-644.AmJRespirCritCareMed,20037Theaimofthisstudywastoevaluatetheeffectofparenteral

nutritioncontainingmedium-andlong-chaintriglycerideson

thefunctionoftherespiratorysystemandtoinvestigatemechanisms

involvedinthisprocess.Westudied13patientswithacute

respiratorydistresssyndrome(ARDS),8receivinglipidand

5placebo,and6withoutARDS,receivinglipid.Bronchoalveolar

lavage(BAL)wasperformedbeforeand1hourafteradministration

oflipidorplacebo.InpatientswithARDS,lipidadministration

resultedindeteriorationofoxygenation(PaO2/FIO2:from129

±37to95±42),complianceofrespiratorysystem

(from39.2±12to33.1±9.2ml/cmH2O),and

pulmonaryvascularresistance(from258±47to321±

58dyne·s·cm-5).IntheBALfluidofthesame

group,anincreaseintotalproteinandphospholipidconcentrations,

phospholipaseactivities,platelet-activatingfactorandneutrophils,

aswellasalterationsinBALlipidprofilewereobserved.No

significantchangeswereobservedinthecontrolorintheARDS-Placebo

groups.Inconclusion,thisstudyindicatesthatadministration

ofmedium-andlong-chaintriglyceridesinpatientswithARDS

causesalterationsinlungfunctionandhemodynamics.Inflammatory

cells,possiblyactivatedbylipids,releasephospholipaseA2

andplatelet-activatingfactor,enhancingedemaformation,inflammation,

andsurfactantalterations.AmJRespirCritCareMed,2004,169:638-644.Theaimofthisstudywastoe38治疗六、其他药物治疗皮质激素在中晚期应用可能对防止肺纤维化有一定作用。对于脂肪栓塞综合征和卡氏肺囊虫肺炎有预防和治疗作用。其他抗炎制剂，如PGE1抗内毒素抗体、IL-1受体抗体、PAF受体拮抗剂、抗TNF抗体等，均需进一步研究。治疗六、其他药物治疗39NEnglJMed2004;351:884-892.NEnglJMed2004;351:884-89240NEnglJMed2004;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;351:884-89241NEnglJMed2004;351:884-892.NEnglJMed2004;351:884-89242MethodsIntwomulticenter,randomized,double-blindtrials

involving448patientswithARDSfromvariouscauses,wecompared

standardtherapyalonewithstandardtherapyplusuptofour

intratrachealdosesofarecombinantsurfactantproteinC–based

surfactantgivenwithinaperiodof24hours.

ResultsTheoverallsurvivalratewas66percent28daysafter

treatment,andthemediannumberofventilator-freedayswas

0(68percentrange,0to26);therewasnosignificantdifference

betweenthegroupsintermsofmortalityortheneedformechanical

ventilation.Patientsreceivingsurfactanthadasignificantly

greaterimprovementinbloodoxygenationduringtheinitial

24hoursoftreatmentthanpatientsreceivingstandardtherapy,

accordingtobothunivariateandmultivariateanalyses.

ConclusionsTheuseofexogenoussurfactantinaheterogeneous

populationofpatientswithARDSdidnotimprovesurvival.Patients

whoreceivedsurfactanthadagreaterimprovementingasexchange

duringthe24-hourtreatmentperiodthanpatientswhoreceived

standardtherapyalone,suggestingthepotentialbenefitof

alongertreatmentcourse.NEnglJMed2004;351:884-892.MethodsIntwomulticenter,ra43ARDS的机械通气一、ARDS的呼吸力学特点

1．肺气容积减少2．病变的非均一性3．肺顺应性降低心脏SPARDS的机械通气一、ARDS的呼吸力学特44ARDS的机械通气二、呼吸机所致肺损伤

1．肺气压伤(barotrauma)2．肺容积伤(volutrauma)3．肺萎陷伤(atelectauma)4．肺生物伤(biotrauma)ARDS的机械通气二、呼吸机所致肺损伤45ARDS的机械通气三、机械通气的策略

1．高呼气末正压策略2．小潮气量策略3．长吸气策略4．肺开放策略ARDS的机械通气三、机械通气的策略46ARDS的机械通气四、通气参数的调节

1．吸氧浓度(FiO2)2．PEEP3．潮气量4．呼吸频率的调节5．吸呼比(I／E)的调节0204060VT（L）LIPUIPARDS的机械通气四、通气参数的调节0247NEnglJMed1998;338:347-354.NEnglJMed1998;338:347-35448NEnglJMed1998;338:347-354.NEnglJMed1998;338:347-35449BackgroundInpatientswiththeacuterespiratorydistresssyndrome,

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.BackgroundInpatientswithth50NEnglJMed2000;342:1301-1308,NEnglJMed2000;342:1301-1351NEnglJMed2000;342:1301-1308,NEnglJMed2000;342:1301-1352BackgroundTraditionalapproachestomechanicalventilation

usetidalvolumesof10to15mlperkilogramofbodyweight

andmaycausestretch-inducedlunginjuryinpatientswithacute

lunginjuryandtheacuterespiratorydistresssyndrome.We

thereforeconductedatrialtodeterminewhetherventilation

withlowertidalvolumeswouldimprovetheclinicaloutcomes

inthesepatients.

ResultsThetrialwasstoppedaftertheenrollmentof861patients

becausemortalitywaslowerinthegrouptreatedwithlower

tidalvolumesthaninthegrouptreatedwithtraditionaltidal

volumes(31.0percentvs.39.8percent,P=0.007),andthenumber

ofdayswithoutventilatoruseduringthefirst28daysafter

randomizationwasgreaterinthisgroup(mean[±SD],

12±11vs.10±11;P=0.007).Themeantidalvolumes

ondays1to3were6.2±0.8and11.8±0.8mlper

kilogramofpredictedbodyweight(P<0.001),respectively,

andthemeanplateaupressureswere25±6and33±8

cmofwater(P<0.001),respectively.

ConclusionsInpatientswithacutelunginjuryandtheacute

respiratorydistresssyndrome,mechanicalventilationwitha

lowertidalvolumethanistraditionallyusedresultsindecreased

mortalityandincreasesthenumberofdayswithoutventilator

use.NEnglJMed2000;342:1301-1308,BackgroundTraditionalapproac53NEnglJMed2004;351:327-336.NEnglJMed2004;351:327-33654NEnglJMed2004;351:327-336.NEnglJMed2004;351:327-33655MethodsWerandomlyassigned549patientswithacutelunginjury

andARDStoreceivemechanicalventilationwitheitherlower

orhigherPEEPlevels,whichweresetaccordingtodifferent

tablesofpredeterminedcombinationsofPEEPandfractionof

inspiredoxygen.

ResultsMean(±SD)PEEPvaluesondays1through4were

8.3±3.2cmofwaterinthelower-PEEPgroupand13.2±3.5

cmofwaterinthehigher-PEEPgroup(P<0.001).Therates

ofdeathbeforehospitaldischargewere24.9percentand27.5

percent,respectively(P=0.48;95percentconfidenceinterval

forthedifferencebetweengroups,–10.0to4.7percent).

Fromday1today28,breathingwasunassistedforameanof

14.5±10.4daysinthelower-PEEPgroupand13.8±10.6

daysinthehigher-PEEPgroup(P=0.50).

ConclusionsTheseresultssuggestthatinpatientswithacute

lunginjuryandARDSwhoreceivemechanicalventilationwith

atidal-volumegoalof6mlperkilogramofpredictedbodyweight

andanend-inspiratoryplateau-pressurelimitof30cmofwater,

clinicaloutcomesaresimilarwhetherlowerorhigherPEEPlevels

areused.NEnglJMed2004;351:327-336.MethodsWerandomlyassigned556NEnglJMed2001;345:568-573,.NEnglJMed2001;345:568-57357NEnglJMed2001;345:568-573,.NEnglJMed2001;345:568-57358NEnglJMed2001;345:568-573,.NEnglJMed2001;345:568-57359MethodsInamulticenter,randomizedtrial,wecomparedconventional

treatment(inthesupineposition)ofpatientswithacutelung

injuryortheacute

respiratory

distress

syndromewithapredefined

strategyofplacingpatientsinapronepositionforsixor

morehoursdailyfor10days.Weenrolled304patients,152

ineachgroup.

ResultsThemortalityratewas23.0percentduringthe10-day

studyperiod,49.3percentatthetimeofdischargefromthe

intensivecareunit,and60.5percentat6months.Therelative

riskofdeathinthepronegroupascomparedwiththesupine

groupwas0.84at