严重ARDS的治疗策略

严重ARDS的治疗策略第1页/共73页什么是ARDS?中华医学会重症医学分会。急性肺损伤/急性呼吸窘迫综合征诊断和治疗指南(2006)。ChinCritCareMed,Dec2006,Vol.18,No112

ALI/ARDS是在严重感染、休克、创伤及烧伤等非心源性疾病过程中,肺毛细血管内皮细胞和肺泡上皮细胞损伤造成弥漫性肺间质及肺泡水肿,导致的急性低氧性呼吸功能不全或衰竭。以肺容积减少、肺顺应性降低、严重的通气/血流比例失调为病理生理特征,临床表现为进行性低氧血症和呼吸窘迫,肺部影像学表现为非均一性的渗出性病变。第2页/共73页第3页/共73页ARDS的关注要点不是一个病，而是一个综合征。可以由一个原发病或诱因导致，也可以是多个诱因共同或序贯作用的结果。ARDS的本质是SIRS，是SIRS的严重阶段；ARDS是MODS或MOF在肺部的表现。“小肺”通气和严重的顽固性低氧血症是其最重要的特征。ARDS的预防远比治疗更有意义.辅助治疗：维持、维护肺脏功能，为原发病的治疗赢得时间。第4页/共73页ARDS的诊断标准目前仍广泛沿用1994年欧美联席会议提出的诊断标准:①急性起病;②氧合指数(PaO2/FiO2)≤200mmHg〔1mmHg=0.133kPa,不管呼气末正压(PEEP)水平〕;③正位X线胸片显示双肺均有斑片状阴影;④肺动脉嵌顿压≤18mmHg,或无左心房压力增高的临床证据。如PaO2/FiO2≤300mmHg且满足上述其他标准,可诊断ALI。第5页/共73页ARDS的基本治疗策略压力控制通气气道峰压＜35cmH2O,平台压＜30cmH2O小潮气量：4-6ml/kgPEEP8-20cmH2O允许性高碳酸血症(Permissivehypercapnia)第6页/共73页严重ARDS的定义当ARDS患者保护性肺通气策略失败,出现顽固性低氧血症和严重酸中毒,肺损伤评分≥3分时,可以认为患者存在严重ARDS,应考虑挽救性治疗措施(Rescuetherapies).第7页/共73页CritCareMed2010Vol.38,No.8第8页/共73页严重ARDS的定义肺损伤评分0分1分2分3分4分PaO2/FiO2≥300225-299175-224100-174＜100胸片实变无1个项限2个项限3个项限4个项限PEEP≤56-89-1112-14≥15顺应性≥8060-7940-5920-39≤19＊肺损伤评分为以上所有项目评分之和CritCareMed2010Vol.38,No.8第9页/共73页严重ARDS的治疗策略-六步法肺复张和高PEEP俯卧位通气(PPV)高频振荡通气(HFOV)一氧化氮吸入(inhaledNO)糖皮质激素glucocorticoid)体外生命支持(ECLS)CritCareMed2010Vol.38,No.8第10页/共73页六步法之一:肺复张和高PEEP第11页/共73页原理：RecruitmentManeuvers(复张手法）和高PEEP可以使陷闭和实变的部分或全部肺泡恢复通气,从而改善氧合,减少反复开放和关闭肺泡导致的肺损伤.风险：肺泡液清除率下降、VALI和血流动力学障碍。临床实施：RM结合高PEEP或单纯高PEEP，应考虑仅应用于危及生命的严重ARDS早期、有低氧血症且平台压30＜cmH2O者。休克、气胸或局限性病变的患者不建议使用使用RM。实施前需要充分容量复苏和镇静。最佳PEEP设置应高于RM前5-10cmH2O，以维持肺开放。实施6-12小时内应反复评价氧合和顺应性是否得到改善，以决定后续治疗措施。CritCareMed2010Vol.38,No.8第12页/共73页常用的RMs控制性肺膨胀(SI)法PEEP递增法压力控制(PCV)法第13页/共73页控制性肺膨胀(SI)法第14页/共73页第15页/共73页如何实施RM?设置FiO2=1.0；等待10分钟；适当镇静；可能需要多次RM。第16页/共73页RM必须终止的情况MAP＜60mmHg或下降幅度＞20mmHg；SaPO2＜88%HR＞130or＜60perminute新的心律失常；第17页/共73页第18页/共73页PEEP递增法第19页/共73页PCV法Pins=40cmH2O,40S,20cmH2OPEEP维持方法一方法二第20页/共73页AmJRespirCritCareMedVol178.pp1156–1163,2008第21页/共73页Rationale:Thereareconflictingdataregardingthesafetyandefficacyofrecruitmentmaneuvers(RMs)inpatientswithacutelunginjury(ALI).Objectives:TosummarizethephysiologiceffectsandadverseeventsinadultpatientswithALIreceivingRMs.Methods:Systematicreviewofcaseseries,observationalstudies,andRCTswithpoolingofstudy-leveldata.

MeasurementsandMainResults:

Fortystudies(1,185patients)metinclusioncriteria.Oxygenation(31studies;636patients)wassignificantlyincreasedafteranRM(PaO2:106versus193mmHg,P50.001;andPaO2/FIO2ratio:139versus251mmHg,P,0.001).Therewerenopersistent,clinicallysignificantchangesinhemodynamicparametersafteranRM.Ventilatoryparameters(32studies;548patients)werenotsignificantlyalteredbyanRM,exceptforhigherPEEPpost-RM(11versus16cmH2O;P50.02).Hypotension(12%)anddesaturation(9%)werethemostcommonadverseevents(31studies;985patients).Seriousadverseevents(e.g.,barotrauma[1%]andarrhythmias[1%])wereinfrequent.Only10(1%)patientshadtheirRMsterminatedprematurelyduetoadverseevents.第22页/共73页第23页/共73页第24页/共73页第25页/共73页第26页/共73页第27页/共73页第28页/共73页第29页/共73页Conclusions:AdultpatientswithALIreceivingRMsexperiencedasignificantincreaseinoxygenation,withfewseriousadverseevents.TransienthypotensionanddesaturationduringRMsiscommonbutisself-limitedwithoutseriousshort-termsequelae.GiventheuncertainbenefitoftransientoxygenationimprovementsinpatientswithALIandthelackofinformationontheirinfluenceonclinicaloutcomes,theroutineuseofRMscannotberecommendedordiscouragedatthistime.RMsshouldbeconsideredforuseonanindividualizedbasisinpatientswithALIwhohavelife-threateninghypoxemia.第30页/共73页六步法之二：俯卧位通气原理:促进肺膨胀不全区域复张。主要机制是通过减轻外部压力，改善肺通气/血流比例。风险:局部并发症,如面部水肿、结膜出血、压疮；翻身导致管道脱落。临床实施：俯卧位通气持续的时间：建议＞20小时。第31页/共73页第32页/共73页Introduction:InpatientswithALIand/orARDS,recentrandomisedcontrolledtrials(RCTs)showedaconsistenttrendofmortalityreductionwithproneventilation.Weupdatedameta-analysisonthistopic.Methods:RCTsthatcomparedventilationofadultpatientswithALI/ARDSinproneversussupinepositionwereincludedinthisstudy-levelmeta-analysis.Analysiswasmadebyarandom-effectsmodel.TheeffectsizeonICUmortalitywascomputedintheoverallincludedstudiesandintwosubgroupsof

studies:thosethatincludedallALIorhypoxemicpatients,andthosethatrestrictedinclusiontoonlyARDSpatients.Arelationshipbetweenstudies’effectsizeanddailypronedurationwassoughtwithmeta-regression.Wealsocomputedtheeffectsofpronepositioningonmajoradverseairwaycomplications.第33页/共73页第34页/共73页第35页/共73页第36页/共73页第37页/共73页Results:SevenRCTs(including1,675adultpts,ofwhom862wereventilatedintheproneposition)wereincluded.ThefourmostrecenttrialsincludedonlyARDSpatients,andalsoappliedthelongestproningdurationsandusedlung-protectiveventilation.Theeffectsofpronepositioningdifferedaccordingtothetypeofstudy.Overall,proneventilationdidnotreduceICUmortality(oddsratio=0.91,95%confidenceinterval=0.75to1.2;P=0.39),butitsignificantlyreducedtheICUmortalityinthefourrecentstudiesthatenrolledonlypatientswithARDS(oddsratio=0.71;95%confidenceinterval=0.5to0.99;P=0.048;numberneededtotreat=11).Metaregressiononallstudiesdisclosedonlyatrendtoexplaineffectvariationbyproneduration(P=0.06).Pronepositioningwasnotassociatedwithastatisticalincreaseinmajorairwaycomplications.Conclusions:LongdurationofventilationinpronepositionsignificantlyreducesICUmortalitywhenonlyARDSpatientsareconsidered.第38页/共73页六步法之三：高频振荡通气(HFOV)原理：使用高平均气道压，使肺泡复张并改善氧合；通气靠一个振荡活塞在平均气道压上下建立高频率（180-900次/分）压力循环，产生小潮气量（1-2.5ML/KG).风险：高压，可导致血流动力学恶化和气压伤；深度镇静和肌松影响气道分泌物的清除，可引起痰栓堵塞。临床实施：在严重低氧血症和/或高气道平台压的ARDS患者早期应用；不建议用于休克、严重气道堵塞、颅内出血、难治疗性气压伤和严重酸中毒患者。CritCareMed2010Vol.38,No.8第39页/共73页

BMJ2010;340:c2327第40页/共73页Objective：TodetermineclinicalandphysiologicaleffectsofHFOVcomparedwithconventionalventilationinpatientswithALI/ARDS.Design：Systematicreviewandmeta-analysis.DatasourcesElectronicdatabasestoMarch

2010,conferenceproceedings,bibliographies,andprimaryinvestigators.StudyselectionRandomisedcontrolledtrialsofhighfrequencyoscillationcomparedwithconventionalventilationinadultsorchildrenwithALI/ARDS.DataselectionThreeauthorsindependentlyextracteddataonclinical,physiological,andsafetyoutcomesaccordingtoapredefinedprotocol.Wecontactedinvestigatorsofallincludedstudiestoclarifymethodsandobtainadditionaldata.Analysesusedrandomeffectsmodels第41页/共73页Characteristicsofpopulationsofpatientsandriskofbias40intrialsincludedinsystematicreview第42页/共73页第43页/共73页Detailsofhighfrequencyoscillation(HFO)andconventionalmechanicalventilation(CMV)intrialsincludedinsystematicreview第44页/共73页Additionalinterventionsorrescuetreatmentsandfundingintrialsofhighfrequencyoscillationandconventionalmechanicalventilationincludedinsystematicreview第45页/共73页Hospitalor30daymortalityinpatientswithacutelunginjury/acuterespiratorydistresssyndromeallocatedtohighfrequencyoscillationorconventionalmechanicalventilation第46页/共73页ClinicaloutcomesandadverseeventsintrialsofhighfrequencyoscillationNooftrialsNoofpatients第47页/共73页Subgroupanalysesbasedonageofpatients,riskofbias,anduseoflungprotectiveventilationincontrolgroups第48页/共73页第49页/共73页第50页/共73页第51页/共73页第52页/共73页Results：8RCTs(n=419patients)wereincluded;almostallpatientshadARDS.Methodologicalqualitywasgood.Theratioofpartialpressureofoxygentoinspiredfractionofoxygenat24,48,and72hourswas16-24%higherinpatientsreceivinghighfrequencyoscillation.

Therewerenosignificantdifferencesinoxygenationindexbecausemeanairwaypressureroseby22-33%inpatientsreceivinghighfrequencyoscillation(P≤0.01).

Inpatientsrandomisedtohighfrequencyoscillation,mortalitywassignificantlyreduced(riskratio0.77,95%confidenceinterval0.61to0.98,P=0.03;sixtrials,365patients,160deaths),andtreatmentfailure(refractoryhypoxaemia,hypercapnoea,hypotension,orbarotrauma)resultingindiscontinuationofassignedtherapywaslesslikely(0.67,0.46to0.99,P=0.04;fivetrials,337patients,73events).Otherrisksweresimilar.Therewassubstantialheterogeneitybetweentrialsforphysiological(I2=21-95%)butnotclinical(I2=0%)outcomes.Pooledresultswerebasedonfeweventsformostclinicaloutcomes.Conclusion：HFOmightimprovesurvivalandisunlikelytocauseharm.Asongoinglargemulticentretrialswillnotbecompletedforseveralyears,thesedatahelpclinicianswhocurrentlyuseorareconsideringthistechniqueforpatientswithARDS.第53页/共73页六步法之四：NO吸入原理：吸入NO通气使部分肺组织血管舒张，血流重新分布，改善通气血流比例，从而改善氧合。临床实施：用于前述措施治疗失败的严重低氧血症患者；吸入NO从1PPM开始，观察氧合改善情况，每30分钟滴定式增加剂量，最高至10PPM；无反应，应停止；有反应，应减量至维持氧合目标的最低剂量；使用时间＜4天。CritCareMed2010Vol.38,No.8第54页/共73页第55页/共73页Background：Acutehypoxaemicrespiratoryfailure(AHRF),definedasALIandARDS,arecriticalconditions.AHRFresultsfromanumberofsystemicconditionsandisassociatedwithhighmortalityandmorbidityinallages.Inhalednitricoxide(INO)hasbeenusedtoimproveoxygenationbutitsroleremainscontroversial.Objectives：TosystematicallyassessthebenefitsandharmsofINOincriticallyillpatientswithAHRF.Searchstrategy：

RCTswereidentifiedfromelectronicdatabases:theCochraneCentralRegisterofControlledTrials(CENTRAL)(TheCochraneLibrary2010,Issue1);MEDLINE;EMBASE;ScienceCitationIndexExpanded;InternationalWebofScience;CINAHL;LILACS;andtheChineseBiomedicalLiteratureDatabase(upto31stJanuary2010).Wecontactedtrialauthors,authorsofpreviousreviews,andmanufacturersinthefield.Selectioncriteria：WeincludedallRCTs,irrespectiveofblindingorlanguage,thatcomparedINOwithnointerventionorplaceboinchildrenoradultswithAHRF.Datacollectionandanalysis：Twoauthorsindependentlyabstracteddataandresolvedanydisagreementsbydiscussion.Wepresentedpooledestimatesoftheinterventioneffectsondichotomousoutcomesasrelativerisks(RR)with95%confidenceintervals(CI).Ourprimaryoutcomemeasurewasallcausemortality.WeperformedsubgroupandsensitivityanalysestoassesstheeffectofINOinadultsandchildrenandonvariousclinicalandphysiologicaloutcomes.Weassessedtheriskofbiasthroughassessmentoftrialmethodologicalcomponentsandtheriskofrandomerrorthroughtrialsequentialanalysis.第56页/共73页Mainresults：Weincluded14RCTswithatotalof1303participants;10ofthesetrialshadahighriskofbias.INOshowednostatisticallysignificanteffectonoverallmortality(40.2%versus38.6%)(RR1.06,95%CI0.93to1.22;I2=0)andinseveralsubgroupandsensitivityanalyses,indicatingrobustresults.LimiteddatademonstratedastatisticallyinsignificanteffectofINOondurationofventilation,ventilatorfreedays,andlengthofstayintheintensivecareunitandhospital.Wefoundastatisticallysignificantbuttransientimprovementinoxygenationinthefirst24hours,expressedastheratioofpartialpressureofoxygentofractionofinspiredoxygenandtheoxygenationindex(MD15.91,95%CI8.25to23.56;I2=25%).However,INOappearstoincreasetheriskofrenalimpairmentamongadults(RR1.59,95%CI1.17to2.16;I2=0)butnottheriskofbleedingormethaemoglobinornitrogendioxideformation.Authors’conclusions：INOcannotberecommendedforpatientswithAHRF.INOresultsinatransientimprovementinoxygenationbutdoesnotreducemortalityandmaybeharmful.第57页/共73页六步法之五：糖皮质激素原理：可以通过抑制中性粒细胞活化、成纤维细胞增殖和胶原沉淀，阻止病情发展为严重和持续的ALI/ARDS。临床实施：用于前述干预措施均失败的严重低氧血症患者；使用低剂量（1mg/kg.d）的甲强龙;3天后氧合指数、顺应性和PaCO2较基线水平无改善，则停用，有效则续用。CritCareMed2010Vol.38,No.8第58页/共73页RespirCare2010;55(1):43–52.第59页/共73页Probabilityofsurvivalandtheproportionofpatientswithpersistentacuterespiratorydistresssyndromewhobecameabletobreathewithoutassistanceduringthefirst180daysafterrandomization.(FromReference12,withpermission.)第60页/共73页MajorFindingsandAssessmentofBenefitorHarmforKeyOutcomesandPhysiologicParametersinPatientsWithARDS,RandomizedtoMethylprednisolone(vsPlacebo)intheCorticosteroidforLate-StageARDSClinicalTrial(ARDSNetwork)第61页/共73页第62页/共73页第63页/共73页Effectofsteroidsonmortalityinacuterespiratorydistresssyndrome(ARDS).第64页/共73页MajorFindingsandAssessmentofBenefitorHarmforKeyOutcomeandPhysiologicParametersinPatientsWithARDSWhoReceivedLow-to-Moderate-DoseCorticosteroids(vsPlacebo)inProspectiveCohortandRandomizedControlledTrials,intheMeta-analysisbyTangetal第65页/共73页ARDS发生的前1-14天，低中剂量的糖皮质激素使用在降低病死率和其他方面对患者是有利的；ARDS发生＞14天，糖皮质激素的作用不确定，不推荐使用；第66页/共73页六步法之六：体外生命支持ECLS原理：用V-V生命支持回路，将患者血液导出并通过膜氧合替代肺进行气体交换。分两种类型：即高流量ECMO和低流量CO2清除回路。临床实施：两种类型均可用于前述治疗措施无效的严重ARDS患者。但不用于有抗凝禁忌或高压机械通气＞1周患者。CritCareMed2010Vol.38,No.8第67页/共73页第68页/共73页ECMOiswidelyacceptedasarescuetherapyinpatientswithacutelife-threateninghypoxemiainthecourseofsevereARDS.However,possiblesideeffectsandcom