呼吸机相关性肺损伤郑州

欧阳彬SICU中山大学附属第一医院,广州呼吸机相关性肺损伤（Ventilatorinducedlunginjury,VILI)(Ventilatorassociatedlunginjury,VALI)中山大学附属第一医院目前一页\总数五十八页\编于七点机械通气挽救了无数患者的生命脊髓灰质炎1952年无呼吸机时死亡率87%，1953年有呼吸机后死亡率15%目前二页\总数五十八页\编于七点但机械通气同时导致了呼吸机相关性肺损伤（VALI）呼吸机诱导膈肌萎缩(VIDD)

呼吸机相关性肺炎(VAP)呼吸机相关性不适（VAUE）目前三页\总数五十八页\编于七点InflammationHemorrhageEdemaFibrosisPulmonarydysfunctionSystemiceffects机械通气导致了怎样的肺损伤？目前四页\总数五十八页\编于七点目前五页\总数五十八页\编于七点1.B.Ouyang（欧阳彬),Jafari,O.Syrkina,C.A.HalesandD.A.Quinn.N-acetyl-L-cysteineinhibitedTGF-productionandreducedlungcollagenformationinventilator-inducedlunginjury.FASEBJournal.2004Mar:18(4):218.11(A323).

2.BinOuyang（欧阳彬),ChoiW,HalesC,QuinnD.TGFup-regulationinvitroandinvivomodelsofVentilatorInducedLungInjury.ATS2003,A622.

3.BinOuyang（欧阳彬）,DeborahA.Quinn,andCharlesA.Hales.StretchInducedGeneExpressioninaninvitromodelofVentilatorInducedLungInjury(VILI).FASEBJournal.2002Mar:16(4):367.10(A410).4.OuyangB（欧阳彬）,ChoukrounG,MatyalR,MascarenhasM,JafariB,BonyentreJV,ForceTandQuinnDA.Stretch-inducedIL-8dependsonc-JunNH2-terminalandnuclearfactor-kappaBinducingkinases.AmJPhysiolLungCellMolPhysiol.2003Aug;285(2):L464-75.

5JafariB,OuyangB（欧阳彬）,LiLF,HalesCAandQuinnDA.Intracellularglutathioneinstretch-inducedcytokinereleasefromalveolartype-2likecells.Respirology.2004Mar;9(1):43-53.

6.

B.Jafari,B.Ouyang（欧阳彬),C.A.HalesandD.A.Quinn.Antioxidantsinhibitstretch-inducedIL-8productionthroughintracellularglutathione.ATS,2002.B82.

7.Li-FuLi,BinOuyang（欧阳彬）,DeborahA.Quinn.Stretch-InducedIL-8isDependentonc-JunN-TerminalKinaseandNuclearFactor-B-InducingKinasePathwaysATS2003,C112.

8.Li-FuLi,BinOuyang（欧阳彬）,BehrouzJafari,CharlesA.Hales,DeborahA.Quinn.StretchInducesIL-8PromoterActivityandIL-8mRNAExpressioninanInVitroModelofVentilatorInducedLungInjury(VILI).FASEBJournal.2002Mar:16(4):367.4

9.QuinnDA,JafariB,LiLF,MascarenhasM,OuyangB（欧阳彬）,SyrkinaO,andHalesCA.PulmonaryEpithelialCells,EndothelialCellsandFibroblastsContributetoLungStretch-InducedCytokineProductionFoundinVentilator-InducedLungInjury(VILI).FASEBJournal.2003,85.1(A88).

10.MascarenhasMM,DayRM,OchoaCD,ChoiWI,YuL,OuyangB（欧阳彬）,GargHG,HalesCAandQuinnDA.Lowmolecularweighthyaluronanfromstretchedlungenhancesinterleukin-8expression.AmJRespirCellMolBiol.2004;30(1):51-60.VILI：我的体会目前六页\总数五十八页\编于七点VentilatorRatMousePigSheep目前七页\总数五十八页\编于七点1.炎症（Inflammation）TidalVolume3ml/kgTidalVolume6ml/kgTidalVolume12ml/kgTidalVolume12ml/kg2003,J.AmPhysio.Lung目前八页\总数五十八页\编于七点TidalVolume7ml/kgfor2hrsTidalVolume20ml/kgfor2hrs2.出血（Hemorrhage）目前九页\总数五十八页\编于七点3.水肿（Edema）ProteinLeakageWaterLeakage2003,AmJ.Respir.CCM目前十页\总数五十八页\编于七点VT20VT7*p<0.05vs.VT7†p<0.05vs.Non-MV*†Collagen(g/mgprotein)*†1509060300Non-MV2hour2ndday3rdday4thday*†Lungtissueharvestedtime(post2hourmechanicalventilation)120VT7VT20††4.肺纤维化（LungFibrosis）2003,ATS,Seattle--VILIMODELOFRATS目前十一页\总数五十八页\编于七点肺纤维化（LungFibrosis）*p<0.05vs.Collagen(Static)†p<0.05vs.TGF-b1(Static)*Static0.5hour1hour4hourStretchCollagen(ug/ml)*TGF-b1(pg/ml)CollagenTGF-b1††1201008060204012010080602040StudyinFibroblasts2004,FASEBJournal目前十二页\总数五十八页\编于七点PaO2(mmHg)PCO2(mmHg)pHa7.457.407.357.307.2575100Non-MV2hour2ndday3rdday4thdayTimeoflungtissueharvested(after2hourMV)255075125**p<0.05vs.VT7VT7VT20**5.肺功能障碍（PulmonaryDysfunction）2002,Appl.J.Physio目前十三页\总数五十八页\编于七点6.全身效应（SystemicEffects）2003,AmJ.Respir.CCM--Proteinuria目前十四页\总数五十八页\编于七点PUC18PUC18GAPDHActinActinGAPDHGAPDHGAPDHIL-1aIL-4GAPDHIL-18IL-8IL-12BMIFTGF3IL-1aIL-4GAPDHIL-18IL-8IL-12BMIFTGF3GMCSFIL-2TNF

IL-17IL-6IL-12Amcp-1TGF2GMCSFIL-2TNF

IL-17IL-6IL-12Amcp-1TGF2GCSFIL-1TNF

IL-16IL-5IL-10LT-TGF1GCSFIL-1TNFIL-16IL-5IL-10LT-TGF1StaticcellsStretchedcellsSystemicEffects2005,MJCLA--Anti-inflammatorycytokine目前十五页\总数五十八页\编于七点TGFb1andTGFb2up-regulationfoundinratserumofVILI**#*p<0.05vsVt7ml/kg#

p<0.05vsControlTGFb1TGFb2ControlVt7ml/kgVt20ml/kgTGFB(pg/ml)目前十六页\总数五十八页\编于七点机械通气导致肺损伤的机制探讨目前十七页\总数五十八页\编于七点TheMechanismofInflammationStretcherAlveolarepithelialcellsBronchialepithelialcellsLungfibroblastsMacrophages目前十八页\总数五十八页\编于七点TheMechanismofInflammation----StudiesinlungepithelialcellsStretchIL-82003,JAMPhysio.目前十九页\总数五十八页\编于七点TheMechanismofInflammation----StudiesinlungepithelialcellsStretchJunKIL-82003,JAMPhysio.目前二十页\总数五十八页\编于七点TheMechanismofInflammation----StudiesinlungepithelialcellsStretchJunKIL-8PlasmaNuclearmRNA,ProteinCellmembraneNIKAP-1NF-kB2003,JAMPhysio.目前二十一页\总数五十八页\编于七点WildType6ml/kgWildType30ml/kgWildType30ml/kg+JNKinhibitorWildType30ml/kg+JNKknockoutTheMechanismofInflammation----StudiesinJunKknockoutmiceVentilationJunKNeutrophils目前二十二页\总数五十八页\编于七点TheMechanismofInflammation----MatrixVentilationHANeutrophils2004,Am.J.Respir目前二十三页\总数五十八页\编于七点TheMechanismofInflammation----FibroblastsVentilationLMWHAIL-8HAS32004,Am.J.Respir目前二十四页\总数五十八页\编于七点TheMechanismofInflammation--OxidantInjuryVentilationGSHIL-8Oxidants2004,Respirology目前二十五页\总数五十八页\编于七点

压力伤（Barotrauma）

Pneumothoraxandemphysema,PIP>50cmH2O

容量伤（Volutrauma）:Dreyfuss,1988(rats),ARDSNetwork,2000

剪切伤（Atelectrauma）:Atelectasis

生物伤（Biotrauma）:Cytokines(IL-8,IL-10,IL-6,TNFa,TGFb),OxidantsGajicetal.CCM2004:Severeinjuriesoccurredinventilatedarea-----Doctorinducedlunginjury呼吸机相关性肺损伤目前二十六页\总数五十八页\编于七点BarotraumaPneumothoraxandemphysema,PIP>50cmH2O1.压力伤:Webb,et.al.:AmRevRDis110:556-65,1974目前二十七页\总数五十八页\编于七点14Peak0PEEP45Peak10PEEP45Peak0PEEPDreyfuss:AmRevRDis148:1194-1203,1993目前二十八页\总数五十八页\编于七点Theaerated,ventralregions(‘babylung’)-Barotrauma目前二十九页\总数五十八页\编于七点

压力伤的减轻:Pneumothoraxandemphysema,PIP>50cmH2O

吸气平台压（IPP）：<30-35cmH2O气道峰压（PIP）：平台压+气道阻力

在容控通气时,设定压力限制

压力支持(PS)带来的损伤>PEEP

跨肺压的意义更大目前三十页\总数五十八页\编于七点Volume,ml800600400200002040DPL02040Pao02040DPescmH2OLimitationofPlateauPressureHeterogenousInvolvementLungandChestWallInvolvement目前三十一页\总数五十八页\编于七点2.容量伤(Volutrauma）:Dreyfuss,1988(rats),ARDSNetwork,2000Theaerated,ventralregions(‘babylung’)-Volutrama目前三十二页\总数五十八页\编于七点NEJM2001;344:1986目前三十三页\总数五十八页\编于七点目前三十四页\总数五十八页\编于七点6cc/kgversus12cc/kg目前三十五页\总数五十八页\编于七点6cc/kgversus12cc/kg31%Mortalitywithsmalltidalvolumes(lowplateaupressure)38.9%Mortalityinconventionaltidalvolumegroup(higherplateaupressures)目前三十六页\总数五十八页\编于七点332patientswithoutARDS

<9ml/kg9-12ml/kg>12ml/kg

ALIARDS17%22%33%

-----DoctorinducedARDS

低潮气量保护正常肺目前三十七页\总数五十八页\编于七点DevelopmentofARDSandTidalVolumeForevery1cc/kgabove6cc/kg,oddsratioofALIincreased1.3目前三十八页\总数五十八页\编于七点3.剪切伤（Atelectrauma）:AtelectasisTheconsolidationandatelectasisTheinterfacebetweenthetwoareas-Atelectrauma目前三十九页\总数五十八页\编于七点AlveolarCollapsing-ReopeningInjuryZEEPPEEPAirwayPressure目前四十页\总数五十八页\编于七点10008006004002000010203040Pressure,cmH2ONEJM2001;344:1986024

6ProtectiveVentilation6004002000SecondsVolume,ml0246ConventionalVentilation8006004002000Volume,mlAlveolaroverdistentionAlveolarcollapse目前四十一页\总数五十八页\编于七点Gattinonietal,AJRCCM1998;158:3PEEPEffect:InfluenceofARDSEtiologyPulmonaryCauseNonPulmonaryCause151050ChangeinVolume,LChangeinStaticTotalRespiratorySystemPressure,cmH2O04010302001.6PEEP010203040目前四十二页\总数五十八页\编于七点目前四十三页\总数五十八页\编于七点BestPEEP:CO,PaO2,FiO2

PEEP55-88-1010-1214-18NHLBARDSclinicaltrialsnetwork,2004,NEJM549patients,28daysPEEP8vs.13cmH2O,NodifferenceBestPEEP目前四十四页\总数五十八页\编于七点EffectofPEEPinARDSRandomized549ARDS/ALIpatients

ARDSNetworkNEJM2004;351(4):327

010203040500.01.0ProbabilityDaysafterRandomization50HighPEEP13.2+3.5cmH2O

LowPEEP8.3+3.2cmH2O

HighvLowPEEP--Age:54v49yr

PO2/FiO2151v165

PEEPnotcustomizedtopathophysiologyChangeinPO2usedtoestimaterecruitment--butmayreflectchangeincardiacoutputratherthanrecruitment目前四十五页\总数五十八页\编于七点RecruitmentManueverOpenlungandkeepthelungopen----Indication:Refractaryhypoxmia----Contra-indication:Emphysema,Pneumothorax目前四十六页\总数五十八页\编于七点LowPercentageofRecruitableLungAirwayPressure,5cmH2OAirwayPressure,45cmH2OGattinonietal,NEJM2006;354:1775PercentageofPotentiallyRecruitableLung*=4%*PotentiallyRecruitableLung=proportionoflungtissueinwhichaerationwasrestoredwhenPawincreasedfrom5to45目前四十七页\总数五十八页\编于七点HigherPercentageofRecruitableLungAirwayPressure,5cmH2OAirwayPressure,45cmH2OGattinonietal,NEJM2006;354:1775PercentageofPotentiallyRecruitableLung*=37%*PotentiallyRecruitableLung=proportionoflungtissueinwhichaerationwasrestoredwhenPawincreasedfrom5to45目前四十八页\总数五十八页\编于七点SuperimposedPressureOpeningPressureInflated0AlveolarCollapse(Reabsorption)20-60cmH2OSmallAirwayCollapse10-20cmH2OConsolidation目前四十九页\总数五十八页\编于七点NewVentilationStrategiesConventionalVentilationStrategyNormalizebloodgases

PaO2PaCO2

pH

NewVentilationStrategyLungProtectiveStrategy

SupportRespirationMinimizingLungInjuryLowtidalvolumeBestPEEPPermissiveHypercapnia目前五十页\总数五十八页\编于七点PermissiveHypercapniaPermissivehypercapnia:PaCO2Contra-indication:HeartFailure,BrainInjuryor