ARDS进展-施焕中.ppt

急性呼吸窘迫综合征,NEnglJMed2003;348:683-693.,NEnglJMed2003;348:683-693.,NEnglJMed2003;348:683-693.,MethodsWeevaluated109survivorsoftheacuterespiratorydistresssyndrome3,6,and12monthsafterdischargefromtheintensivecareunit.Ateachvisit,patientswereinterviewedandunderwentaphysicalexamination,pulmonary-functiontesting,asix-minutewalktest,andaquality-of-lifeevaluation.ResultsPatientswhosurvivedtheacuterespiratorydistresssyndromewereyoung(medianage,45years)andseverelyill(medianAcutePhysiology,Age,andChronicHealthEvaluationscore,23)andhadalongstayintheintensivecareunit(median,25days).Patientshadlost18percentoftheirbase-linebodyweightbythetimetheyweredischargedfromtheintensivecareunitandstatedthatmuscleweaknessandfatiguewerethereasonsfortheirfunctionallimitation.Lungvolumeandspirometricmeasurementswerenormalby6months,butcarbonmonoxidediffusioncapacityremainedlowthroughoutthe12-monthfollow-up.Nopatientsrequiredsupplementaloxygenat12months,but6percentofpatientshadarterialoxygensaturationvaluesbelow88percentduringexercise.ThemedianscoreforthephysicalroledomainoftheMedicalOutcomesStudy36-itemShort-FormGeneralHealthSurvey(ahealth-relatedquality-of-lifemeasure)increasedfrom0at3monthsto25at12months(scoreinthenormalpopulation,84).Thedistancewalkedinsixminutesincreasedfromamedianof281mat3monthsto422mat12months;allvalueswerelowerthanpredicted.Theabsenceofsystemiccorticosteroidtreatment,theabsenceofillnessacquiredduringtheintensivecareunitstay,andrapidresolutionoflunginjuryandmultiorgandysfunctionwereassociatedwithbetterfunctionalstatusduringtheone-yearfollow-up.ConclusionsSurvivorsoftheacuterespiratorydistresssyndromehavepersistentfunctionaldisabilityoneyearafterdischargefromtheintensivecareunit.Mostpatientshaveextrapulmonaryconditions,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-1receptorantagonist,solubletumornecrosisfactorreceptor,autoantibodiesagainstinterleukin-8,andcytokinessuchasinterleukin-10and11(notshown).Theinfluxofprotein-richedemafluidintothealveolushasledtotheinactivationofsurfactant.MIFdenotesmacrophageinhibitoryfactor.,发病机制,管状髓磷脂,发病机制,SurfactantProductionandRecyclingintheNormalAlveolus(PanelA)andChangesinSurfactantMetabolisminAcuteLungInjury(PanelB).Inthenormalalveolus,surfactantissynthesizedandpackagedintolamellarbodiesinthecellcytoplasm.Theselamellarbodiesthenmigratetothecellmembrane,withwhichtheyfuse,andthenarereleasedintotheairfluidinterfacewithinthealveolus.Theysubsequentlyformanintermediatetubularstageofsurfactantcalledtubularmyelin,whichfinallyproducesthefunctionalcoatinglayer.Surfactantproteinsarealsoinvolvedinthecoatingprocess.Surfactantrecyclingoccursthroughtheendocytosisofsmallvesicles.Alterationsinsurfactantmetabolism(PanelB)mayoccuratanyofthesesteps.TheexactpathophysiologyofsurfactantmetabolisminARDShasnotbeenfullyestablished,butitislikelytoconsistofboththedestructionandthestructuralalterationofsurfactantlipidsandproteincausedbytheinflammatorymilieuoftheinjuredairspace.Inaddition,synthesisandrecyclingofsurfactantarelikelytobereducedanditsfunctionimpairedbytheaccumulationofproteinaceousmaterialwithinthealveolus.TNFdenotestumornecrosisfactor.,病理,2d,14d,14d,病理,4d,14d,PanelAshowsalung-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。,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/FiO2300mmHg；ARDS时PaO2/FiO2200mmHg。四、胸部X线检查两肺浸润影响。五、PCWP18mmHg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。,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PAAO2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,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,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。,2004-07-27,2004-08-12,2004-08-14,2004-08-15,2004-08-17,2004-08-18,2004-08-20,2004-08-23,2004-08-25,2004-08-27,2004-08-30,2004-08-31,2004-09-01,2004-09-03,2004-09-07,2004-09-15,2004-09-20,2004-09-23,2004-09-27,2004-09-30,2004-10-08,2004-10-17,2004-10-24,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,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。,CritCareMed2002;30:2175-2182.,Figure1.Changeinserumtotalproteinduringthestudy,withthetreatmentperiodidentifiedbytheshadedarea.Pointsrepresentmean,witherrorbarsindicatingsem.Figure3.Changeinoxygenation,asmeasuredbythePao2/Fio2ratio(meansem),withthetreatmentperiodidentifiedbytheshadedarea.*Significantwithin-groupchangefrombaseline;timepointswithsignificantbetween-groupdifferences.Amaximumof25%ofdatapointsmaybeabsentfromcalculationsrepresentedafterday5.Figure4.Changeinthemeanarterialpressure(mmHg)/heartrate(beats/min)ratio(MAP/HRratio)frombaseline.Thetreatmentperiodisindicatedbytheshadedarea.Pointsrepresentmeanvalues,witherrorbarsdepictingsem(meansem)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.,6997patients,BackgroundItremainsuncertainwhetherthechoiceofresuscitationfluidforpatientsinintensivecareunits(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(6.56.6inthealbumingroupand6.26.2inthesalinegroup,P=0.44),daysspentinthehospital(15.39.6and15.69.6,respectively;P=0.30),daysofmechanicalventilation(4.56.1and4.35.7,respectively;P=0.74),ordaysofrenal-replacementtherapy(0.52.3and0.42.0,respectively;P=0.41).ConclusionsInpatientsintheICU,useofeither4percentalbuminornormalsalineforfluidresuscitationresultsinsimilaroutcomesat28days.,NEnglJMed2004;350:2247-2256.,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,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。,AmJRespirCritCareMed,2004,169:638-644.,Theaimofthisstudywastoevaluatetheeffectofparenteralnutritioncontainingmedium-andlong-chaintriglyceridesonthefunctionoftherespiratorysystemandtoinvestigatemechanismsinvolvedinthisprocess.Westudied13patientswithacuterespiratorydistresssyndrome(ARDS),8receivinglipidand5placebo,and6withoutARDS,receivinglipid.Bronchoalveolarlavage(BAL)wasperformedbeforeand1hourafteradministrationoflipidorplacebo.InpatientswithARDS,lipidadministrationresultedindeteriorationofoxygenation(PaO2/FIO2:from12937to9542),complianceofrespiratorysystem(from39.212to33.19.2ml/cmH2O),andpulmonaryvascularresistance(from25847to32158dynescm-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。,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,wecomparedstandardtherapyalonewithstandardtherapyplusuptofourintratrachealdosesofarecombinantsurfactantproteinCbasedsurfactantgivenwithinaperiodof24hours.ResultsTheoverallsurvivalratewas66percent28daysaftertreatment,andthemediannumberofventilator-freedayswas0(68percentrange,0to26);therewasnosignificantdifferencebetweenthegroupsintermsofmortalityortheneedformechanicalventilation.Patientsreceivingsurfactanthadasignificantlygreaterimprovementinbloodoxygenationduringtheinitial24hoursoftreatmentthanpatientsreceivingstandardtherapy,accordingtobothunivariateandmultivariateanalyses.ConclusionsTheuseofexogenoussurfactantinaheterogeneouspopulationofpatientswithARDSdidnotimprovesurvival.Patientswhoreceivedsurfactanthadagreaterimprovementingasexchangeduringthe24-hourtreatmentperiodthanpatientswhoreceivedstandardtherapyalone,suggestingthepotentialbenefitofalongertreatmentcourse.,NEnglJMed2004;351:884-892.,ARDS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,ARDS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,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,四、通气参数的调节1吸氧浓度(FiO2)2PEEP3潮气量4呼吸频率的调节5吸呼比(IE)的调节,0,20,40,60,0.2,0.4,0.6,VT（L）,LIP,UIP,NEnglJMed1998;338:347-354.,NEnglJMed1998;338:347-354.,BackgroundInpatientswiththeacuterespiratorydistresssyndrome,massivealveolarcollapseandcycliclungreopeningandoverdistentionduringmechanicalventilationmayperpetuatealveolarinjury.Wedeterminedwhetheraventilatorystrategydesignedtominimizesuchlunginjuriescouldreducenotonlypulmonarycomplicationsbutalsomortalityat28daysinpatientswiththeacuterespiratorydistresssyndrome.MethodsWerandomlyassigned53patientswithearlyacuterespiratorydistresssyndrome(including28describedpreviously),allofwhomwerereceivingidenticalhemodynamicandgeneralsupport,toconventionalorprotectivemechanicalventilation.Conventionalventilationwasbasedonthestrategyofmaintainingthelowestpositiveend-expiratorypressure(PEEP)foracceptableoxygenation,withatidalvolumeof12mlperkilogramofbodyweightandnormalarterialcarbondioxidelevels(35to38mmHg).Protectiveventilationinvolvedend-expiratorypressuresabovethelowerinflectionpointonthestaticpressurevolumecurve,atidalvolumeoflessthan6mlperkilogram,drivingpressuresoflessthan20cmofwaterabovethePEEPvalue,permissivehypercapnia,andpreferentialuseofpressure-limitedventilatorymodes.ResultsAfter28days,11of29patients(38percent)intheprotective-ventilationgrouphaddied,ascomparedwith17of24(71percent)intheconventional-ventilationgroup(P0.001).Theratesofweaningfrommechanicalventilationwere66percentintheprotective-ventilationgroupand29percentintheconventional-ventilationgroup(P=0.005);theratesofclinicalbarotraumawere7percentand42percent,respectively(P=0.02),despitetheuseofhigherPEEPandmeanairwaypressuresintheprotective-ventilationgroup.Thedifferenceinsurvivaltohospitaldischargewasnotsignificant;13of29patients(45percent)intheprotective-ventilationgroupdiedinthehospital,ascomparedwith17of24intheconventional-ventilationgroup(71percent,P=0.37).ConclusionsAscomparedwithconventionalventilation,theprotectivestrategywasassociatedwithimprovedsurvivalat28days,ahigherrateofweaningfrommechanicalventilation,andalowerrateofbarotraumainpatientswiththeacuterespiratorydistresssyndrome.Protectiveventilationwasnotassociatedwithahigherrateofsurvivaltohospitaldischarge.,NEnglJMed1998;338:347-354.,NEnglJMed2000;342:1301-13