呼吸機(jī)相關(guān)性肺損傷鄭州

歐陽彬SICU中山大學(xué)附屬第一醫(yī)院,廣州呼吸機(jī)相關(guān)性肺損傷（Ventilatorinducedlunginjury,VILI)(Ventilatorassociatedlunginjury,VALI)中山大學(xué)附屬第一醫(yī)院本文檔共58頁；當(dāng)前第1頁；編輯于星期二\11點(diǎn)42分機(jī)械通氣挽救了無數(shù)患者的生命脊髓灰質(zhì)炎1952年無呼吸機(jī)時(shí)死亡率87%，1953年有呼吸機(jī)后死亡率15%本文檔共58頁；當(dāng)前第2頁；編輯于星期二\11點(diǎn)42分但機(jī)械通氣同時(shí)導(dǎo)致了呼吸機(jī)相關(guān)性肺損傷（VALI）呼吸機(jī)誘導(dǎo)膈肌萎縮(VIDD)

呼吸機(jī)相關(guān)性肺炎(VAP)呼吸機(jī)相關(guān)性不適（VAUE）本文檔共58頁；當(dāng)前第3頁；編輯于星期二\11點(diǎn)42分InflammationHemorrhageEdemaFibrosisPulmonarydysfunctionSystemiceffects機(jī)械通氣導(dǎo)致了怎樣的肺損傷？本文檔共58頁；當(dāng)前第4頁；編輯于星期二\11點(diǎn)42分本文檔共58頁；當(dāng)前第5頁；編輯于星期二\11點(diǎn)42分1.B.Ouyang（歐陽彬),Jafari,O.Syrkina,C.A.HalesandD.A.Quinn.N-acetyl-L-cysteineinhibitedTGF-productionandreducedlungcollagenformationinventilator-inducedlunginjury.FASEBJournal.2004Mar:18(4):218.11(A323).

2.BinOuyang（歐陽彬),ChoiW,HalesC,QuinnD.TGFup-regulationinvitroandinvivomodelsofVentilatorInducedLungInjury.ATS2003,A622.

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

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

6.

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

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

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

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

10.MascarenhasMM,DayRM,OchoaCD,ChoiWI,YuL,OuyangB（歐陽彬）,GargHG,HalesCAandQuinnDA.Lowmolecularweighthyaluronanfromstretchedlungenhancesinterleukin-8expression.AmJRespirCellMolBiol.2004;30(1):51-60.VILI：我的體會(huì)本文檔共58頁；當(dāng)前第6頁；編輯于星期二\11點(diǎn)42分VentilatorRatMousePigSheep本文檔共58頁；當(dāng)前第7頁；編輯于星期二\11點(diǎn)42分1.炎癥（Inflammation）TidalVolume3ml/kgTidalVolume6ml/kgTidalVolume12ml/kgTidalVolume12ml/kg2003,J.AmPhysio.Lung本文檔共58頁；當(dāng)前第8頁；編輯于星期二\11點(diǎn)42分TidalVolume7ml/kgfor2hrsTidalVolume20ml/kgfor2hrs2.出血（Hemorrhage）本文檔共58頁；當(dāng)前第9頁；編輯于星期二\11點(diǎn)42分3.水腫（Edema）ProteinLeakageWaterLeakage2003,AmJ.Respir.CCM本文檔共58頁；當(dāng)前第10頁；編輯于星期二\11點(diǎn)42分VT20VT7*p<0.05vs.VT7?p<0.05vs.Non-MV*?Collagen(g/mgprotein)*?1509060300Non-MV2hour2ndday3rdday4thday*?Lungtissueharvestedtime(post2hourmechanicalventilation)120VT7VT20??4.肺纖維化（LungFibrosis）2003,ATS,Seattle--VILIMODELOFRATS本文檔共58頁；當(dāng)前第11頁；編輯于星期二\11點(diǎn)42分肺纖維化（LungFibrosis）*p<0.05vs.Collagen(Static)?p<0.05vs.TGF-b1(Static)*Static0.5hour1hour4hourStretchCollagen(ug/ml)*TGF-b1(pg/ml)CollagenTGF-b1??1201008060204012010080602040StudyinFibroblasts2004,FASEBJournal本文檔共58頁；當(dāng)前第12頁；編輯于星期二\11點(diǎn)42分PaO2(mmHg)PCO2(mmHg)pHa7.457.407.357.307.2575100Non-MV2hour2ndday3rdday4thdayTimeoflungtissueharvested(after2hourMV)255075125**p<0.05vs.VT7VT7VT20**5.肺功能障礙（PulmonaryDysfunction）2002,Appl.J.Physio本文檔共58頁；當(dāng)前第13頁；編輯于星期二\11點(diǎn)42分6.全身效應(yīng)（SystemicEffects）2003,AmJ.Respir.CCM--Proteinuria本文檔共58頁；當(dāng)前第14頁；編輯于星期二\11點(diǎn)42分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本文檔共58頁；當(dāng)前第15頁；編輯于星期二\11點(diǎn)42分TGFb1andTGFb2up-regulationfoundinratserumofVILI**#*p<0.05vsVt7ml/kg#

p<0.05vsControlTGFb1TGFb2ControlVt7ml/kgVt20ml/kgTGFB(pg/ml)本文檔共58頁；當(dāng)前第16頁；編輯于星期二\11點(diǎn)42分機(jī)械通氣導(dǎo)致肺損傷的機(jī)制探討本文檔共58頁；當(dāng)前第17頁；編輯于星期二\11點(diǎn)42分TheMechanismofInflammationStretcherAlveolarepithelialcellsBronchialepithelialcellsLungfibroblastsMacrophages本文檔共58頁；當(dāng)前第18頁；編輯于星期二\11點(diǎn)42分TheMechanismofInflammation----StudiesinlungepithelialcellsStretchIL-82003,JAMPhysio.本文檔共58頁；當(dāng)前第19頁；編輯于星期二\11點(diǎn)42分TheMechanismofInflammation----StudiesinlungepithelialcellsStretchJunKIL-82003,JAMPhysio.本文檔共58頁；當(dāng)前第20頁；編輯于星期二\11點(diǎn)42分TheMechanismofInflammation----StudiesinlungepithelialcellsStretchJunKIL-8PlasmaNuclearmRNA,ProteinCellmembraneNIKAP-1NF-kB2003,JAMPhysio.本文檔共58頁；當(dāng)前第21頁；編輯于星期二\11點(diǎn)42分WildType6ml/kgWildType30ml/kgWildType30ml/kg+JNKinhibitorWildType30ml/kg+JNKknockoutTheMechanismofInflammation----StudiesinJunKknockoutmiceVentilationJunKNeutrophils本文檔共58頁；當(dāng)前第22頁；編輯于星期二\11點(diǎn)42分TheMechanismofInflammation----MatrixVentilationHANeutrophils2004,Am.J.Respir本文檔共58頁；當(dāng)前第23頁；編輯于星期二\11點(diǎn)42分TheMechanismofInflammation----FibroblastsVentilationLMWHAIL-8HAS32004,Am.J.Respir本文檔共58頁；當(dāng)前第24頁；編輯于星期二\11點(diǎn)42分TheMechanismofInflammation--OxidantInjuryVentilationGSHIL-8Oxidants2004,Respirology本文檔共58頁；當(dāng)前第25頁；編輯于星期二\11點(diǎn)42分

壓力傷（Barotrauma）

Pneumothoraxandemphysema,PIP>50cmH2O

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

剪切傷（Atelectrauma）:Atelectasis

生物傷（Biotrauma）:Cytokines(IL-8,IL-10,IL-6,TNFa,TGFb),OxidantsGajicetal.CCM2004:Severeinjuriesoccurredinventilatedarea-----Doctorinducedlunginjury呼吸機(jī)相關(guān)性肺損傷本文檔共58頁；當(dāng)前第26頁；編輯于星期二\11點(diǎn)42分BarotraumaPneumothoraxandemphysema,PIP>50cmH2O1.壓力傷:Webb,et.al.:AmRevRDis110:556-65,1974本文檔共58頁；當(dāng)前第27頁；編輯于星期二\11點(diǎn)42分14Peak0PEEP45Peak10PEEP45Peak0PEEPDreyfuss:AmRevRDis148:1194-1203,1993本文檔共58頁；當(dāng)前第28頁；編輯于星期二\11點(diǎn)42分Theaerated,ventralregions(‘babylung’)-Barotrauma本文檔共58頁；當(dāng)前第29頁；編輯于星期二\11點(diǎn)42分

壓力傷的減輕:Pneumothoraxandemphysema,PIP>50cmH2O

吸氣平臺(tái)壓（IPP）：<30-35cmH2O氣道峰壓（PIP）：平臺(tái)壓+氣道阻力

在容控通氣時(shí),設(shè)定壓力限制

壓力支持(PS)帶來的損傷>PEEP

跨肺壓的意義更大本文檔共58頁；當(dāng)前第30頁；編輯于星期二\11點(diǎn)42分Volume,ml800600400200002040DPL02040Pao02040DPescmH2OLimitationofPlateauPressureHeterogenousInvolvementLungandChestWallInvolvement本文檔共58頁；當(dāng)前第31頁；編輯于星期二\11點(diǎn)42分2.容量傷(Volutrauma）:Dreyfuss,1988(rats),ARDSNetwork,2000Theaerated,ventralregions(‘babylung’)-Volutrama本文檔共58頁；當(dāng)前第32頁；編輯于星期二\11點(diǎn)42分NEJM2001;344:1986本文檔共58頁；當(dāng)前第33頁；編輯于星期二\11點(diǎn)42分本文檔共58頁；當(dāng)前第34頁；編輯于星期二\11點(diǎn)42分6cc/kgversus12cc/kg本文檔共58頁；當(dāng)前第35頁；編輯于星期二\11點(diǎn)42分6cc/kgversus12cc/kg31%Mortalitywithsmalltidalvolumes(lowplateaupressure)38.9%Mortalityinconventionaltidalvolumegroup(higherplateaupressures)本文檔共58頁；當(dāng)前第36頁；編輯于星期二\11點(diǎn)42分332patientswithoutARDS

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

ALIARDS17%22%33%

-----DoctorinducedARDS

低潮氣量保護(hù)正常肺本文檔共58頁；當(dāng)前第37頁；編輯于星期二\11點(diǎn)42分DevelopmentofARDSandTidalVolumeForevery1cc/kgabove6cc/kg,oddsratioofALIincreased1.3本文檔共58頁；當(dāng)前第38頁；編輯于星期二\11點(diǎn)42分3.剪切傷（Atelectrauma）:AtelectasisTheconsolidationandatelectasisTheinterfacebetweenthetwoareas-Atelectrauma本文檔共58頁；當(dāng)前第39頁；編輯于星期二\11點(diǎn)42分AlveolarCollapsing-ReopeningInjuryZEEPPEEPAirwayPressure本文檔共58頁；當(dāng)前第40頁；編輯于星期二\11點(diǎn)42分10008006004002000010203040Pressure,cmH2ONEJM2001;344:1986024

6ProtectiveVentilation6004002000SecondsVolume,ml0246ConventionalVentilation8006004002000Volume,mlAlveolaroverdistentionAlveolarcollapse本文檔共58頁；當(dāng)前第41頁；編輯于星期二\11點(diǎn)42分Gattinonietal,AJRCCM1998;158:3PEEPEffect:InfluenceofARDSEtiologyPulmonaryCauseNonPulmonaryCause151050ChangeinVolume,LChangeinStaticTotalRespiratorySystemPressure,cmH2O04010302000.80.41.21.6PEEP010203040本文檔共58頁；當(dāng)前第42頁；編輯于星期二\11點(diǎn)42分本文檔共58頁；當(dāng)前第43頁；編輯于星期二\11點(diǎn)42分BestPEEP:CO,PaO2,FiO2

PEEP55-88-1010-1214-18NHLBARDSclinicaltrialsnetwork,2004,NEJM549patients,28daysPEEP8vs.13cmH2O,NodifferenceBestPEEP本文檔共58頁；當(dāng)前第44頁；編輯于星期二\11點(diǎn)42分EffectofPEEPinARDSRandomized549ARDS/ALIpatients

ARDSNetworkNEJM2004;351(4):327

010203040500.00.70.80.91.0ProbabilityDaysafterRandomization50HighPEEP13.2+3.5cmH2O

LowPEEP8.3+3.2cmH2O

HighvLowPEEP--Age:54v49yr

PO2/FiO2151v165

PEEPnotcustomizedtopathophysiologyChangeinPO2usedtoestimaterecruitment--butmayreflectchangeincardiacoutputratherthanrecruitment本文檔共58頁；當(dāng)前第45頁；編輯于星期二\11點(diǎn)42分RecruitmentManueverOpenlungandkeepthelungopen----Indication:Refractaryhypoxmia----Contra-indication:Emphysema,Pneumothorax本文檔共58頁；當(dāng)前第46頁；編輯于星期二\11點(diǎn)42分LowPercentageofRecruitableLungAirwayPressure,5cmH2OAirwayPressure,45cmH2OGattinonietal,NEJM2006;354:1775PercentageofPotentiallyRecruitableLung*=4%*PotentiallyRecruitableLung=proportionoflungtissueinwhichaerationwasrestoredwhenPawincreasedfrom5to45本文檔共58頁；當(dāng)前第47頁；編輯于星期二\11點(diǎn)42分HigherPercentageofRecruitableLungAirwayPressure,5cmH2OAirwayPressure,45cmH2OGattinonietal,NEJM2006;354:1775PercentageofPotentiallyRecruitableLung*=37%*PotentiallyRecruitableLung=proportionoflungtissueinwhichaerationwasrestoredwhenPawincreasedfrom5to45本文檔共58頁；當(dāng)前第48頁；編輯于星期二\11點(diǎn)42分SuperimposedPressureOpeningPressureInflated0AlveolarCollapse(Reabsorption)20-60cmH2OSmallAirwayCollapse10-20cmH2OConsolidation本文檔共58頁；當(dāng)前第49頁；編輯于星期二\11點(diǎn)42分NewVentilationStrategiesConventionalVentilationStrategyNormalizebloodgases

PaO2PaCO2

pH

NewVentilationStrategyLungProtectiveStrategy

SupportRespirationMinimizingLungInjuryLowtidalvolumeBestPEEPPermissiveHypercapnia本文檔共58頁；當(dāng)前第50頁；編輯于星期二\11點(diǎn)42分PermissiveHypercapniaPermissivehypercapnia:PaCO2Contra-indication:HeartFailure,BrainInjuryorbrainoperation