呼吸機(jī)相關(guān)性肺損傷2014-11-22鄭州

1、歐陽(yáng)彬歐陽(yáng)彬 SICU 中山大學(xué)附屬第一醫(yī)院中山大學(xué)附屬第一醫(yī)院, 廣州廣州呼吸機(jī)相關(guān)性肺損傷呼吸機(jī)相關(guān)性肺損傷（Ventilator induced lung injury, VILI) (Ventilator associated lung injury, VALI) 中中山山大大學(xué)學(xué)附附屬屬第第一一醫(yī)醫(yī)院院v機(jī)械通氣挽救了無(wú)數(shù)患者的生命機(jī)械通氣挽救了無(wú)數(shù)患者的生命v脊髓灰質(zhì)炎脊髓灰質(zhì)炎 1952年無(wú)呼吸機(jī)時(shí)年無(wú)呼吸機(jī)時(shí) 死亡率死亡率 87%， 1953年年 有呼吸機(jī)后有呼吸機(jī)后 死亡率死亡率 15%但機(jī)械通氣同時(shí)導(dǎo)致了但機(jī)械通氣同時(shí)導(dǎo)致了 呼吸機(jī)相關(guān)性肺損傷（呼吸機(jī)相關(guān)性肺損傷（VALI

2、） 呼吸機(jī)誘導(dǎo)膈肌萎縮呼吸機(jī)誘導(dǎo)膈肌萎縮(VIDD) 呼吸機(jī)相關(guān)性肺炎呼吸機(jī)相關(guān)性肺炎(VAP) 呼吸機(jī)相關(guān)性不適（呼吸機(jī)相關(guān)性不適（VAUE）u Inflammationu Hemorrhageu Edemau Fibrosisu Pulmonary dysfunctionu Systemic effects 1. B. Ouyang（歐陽(yáng)彬（歐陽(yáng)彬), Jafari, O. Syrkina, C.A. Hales and D.A. Quinn. N-acetyl-L-cysteine inhibited TGF- production and reduced lung collagen f

3、ormation in ventilator-induced lung injury. FASEB Journal. 2004 Mar: 18(4): 218.11 (A323). 2. Bin Ouyang（歐陽(yáng)彬（歐陽(yáng)彬), Choi W, Hales C, Quinn D. TGF up-regulation in vitro and in vivo models of Ventilator Induced Lung Injury. ATS 2003, A622. 3. Bin Ouyang（歐陽(yáng)彬）（歐陽(yáng)彬）, Deborah A. Quinn, and Charles A. Hale

4、s. Stretch Induced Gene Expression in an in vitro model of Ventilator Induced Lung Injury (VILI). FASEB Journal. 2002 Mar: 16(4): 367.10 (A410). 4. Ouyang B（歐陽(yáng)彬）（歐陽(yáng)彬）, Choukroun G, Matyal R, Mascarenhas M, Jafari B, Bonyentre JV, Force T and Quinn DA. Stretch-induced IL-8 depends on c-Jun NH2-termin

5、al and nuclear factor-kappaB inducing kinases. Am J Physiol Lung Cell Mol Physiol. 2003 Aug; 285(2): L464-75. 5 Jafari B, Ouyang B（歐陽(yáng)彬）（歐陽(yáng)彬）, Li LF, Hales CA and Quinn DA. Intracellular glutathione in stretch-induced cytokine release from alveolar type-2 like c ells. Respirology. 2004 Mar; 9(1): 43-

6、53. 6. B. Jafari, B. Ouyang（歐陽(yáng)彬（歐陽(yáng)彬), C. A. Hales and D. A. Quinn. Antioxidants inhibit stretch-induced IL-8 production through intracellular glutathione. ATS, 2002. B82. 7. Li-Fu Li, Bin Ouyang（歐陽(yáng)彬）（歐陽(yáng)彬）, Deborah A. Quinn. Stretch-Induced IL-8 is Dependent on c-Jun N-Terminal Kinase and Nuclear Fac

7、tor- B-Inducing Kinase Pathways ATS 2003, C112. 8. Li-Fu Li, Bin Ouyang（歐陽(yáng)彬）（歐陽(yáng)彬）, Behrouz Jafari, Charles A. Hales, Deborah A. Quinn. Stretch Induces IL-8 Promoter Activity and IL-8 mRNA Expression in an In Vitro Model of Ventilator Induced Lung Injury (VILI). FASEB Journal. 2002 Mar: 16(4): 367.4

8、9. Quinn DA, Jafari B, Li LF, Mascarenhas M, Ouyang B（歐陽(yáng)彬）（歐陽(yáng)彬）, Syrkina O, and Hales CA. Pulmonary Epithelial Cells, Endothelial Cells and Fibroblasts Contribute to Lung Stretch- Induced Cytokine Production Found in Ventilator-Induced Lung Injury (VILI).FASEB Journal. 2003, 85.1 (A88). 10. Mascaren

9、has MM, Day RM, Ochoa CD, Choi WI, Yu L, Ouyang B（歐陽(yáng)彬）（歐陽(yáng)彬）, Garg HG, Hales CA and Quinn DA. Low molecular weight hyaluronan from stretched lung enhances interleukin-8 expression. Am J Respir Cell Mol Biol. 2004; 30 (1): 51-60. VILI：我的體會(huì)：我的體會(huì)VentilatorRatMousePigSheep1. 炎癥（炎癥（Inflammation）Tidal Volu

10、me 3 ml/kgTidal Volume 6 ml/kgTidal Volume 12 ml/kgTidal Volume 12 ml/kg2003, J. Am Physio. LungTidal Volume 7 ml/kg for 2hrsTidal Volume 20 ml/kg for 2hrs2. 出血（出血（Hemorrhage）3. 水腫水腫（Edema）Protein LeakageWater Leakage2003, Am J. Respir. CCMVT 20VT 7 * p 0.05 vs. VT 7 p 0.05 vs. Non-MV* Collagen (g/m

11、g protein)* 1509060300Non-MV2 hour2nd day3rd day4th day* Lung tissue harvested time (post 2 hour mechanical ventilation)120VT 7VT 204. 肺纖維化（肺纖維化（Lung Fibrosis）2003, ATS, Seattle- VILI MODEL OF RATS肺纖維化肺纖維化 （Lung Fibrosis）* p 0.05 vs. Collagen(Static) p 0.05 vs. TGF-1(Static)*Static 0.5 hour 1 hour 4

12、 hour StretchCollagen (ug/ml)*TG F-1 (pg/ml)CollagenTGF-11201008060204012010080602040Study in Fibroblasts2004, FASEB JournalPaO2 (mmHg)PCO2 (mmHg)pHa7.457.407.357.307.2575100Non-MV2 hour2nd day3rd day4th dayTime of lung tissue harvested (after 2 hour MV)255075125* * p 0.05 vs. VT 7 VT 7VT 20*5. 肺功能障

13、礙肺功能障礙（Pulmonary Dysfunction）2002, Appl. J. Physio6. 全身效應(yīng)（全身效應(yīng)（Systemic Effects）2003, Am J. Respir. CCM- ProteinuriaPUC18PUC18GAPDHActinActinGAPDHGAPDHGAPDHIL-1aIL-4GAPDHIL-18IL-8IL-12BMIFTGF 3IL-1aIL-4GAPDHIL-18IL-8IL-12BMIFTGF 3GMCSFIL-2TNF IL-17IL-6IL-12Amcp-1TGF 2GMCSFIL-2TNF IL-17IL-6IL-12Amcp-

14、1TGF 2GCSFIL-1 TNF IL-16IL-5IL-10LT- TGF 1GCSFIL-1 TNF IL-16IL-5IL-10LT- TGF 1Static cellsStretched cellsSystemic Effects2005, MJCLA- Anti-inflammatory cytokineTGF 1 1 and TGF 2 2 up-regulation found in rat serum of VILI01020304050607080*#* p 0.05 vs Vt 7ml/kg# p 50 cmH2O 容量傷（容量傷（Volutrauma）: Dreyfu

15、ss, 1988 (rats) , ARDS Network, 2000 剪切傷（剪切傷（Atelectrauma）: Atelectasis 生物傷（生物傷（Biotrauma）: Cytokines (IL-8, IL-10, IL-6, TNFa, TGFb), Oxidants Gajic et al. CCM 2004 : Severe injuries occurred in ventilated area -Doctor induced lung injury呼吸機(jī)相關(guān)性肺損傷呼吸機(jī)相關(guān)性肺損傷BarotraumaPneumothorax and emphysema, PIP 5

16、0 cmH2O1. 壓力傷壓力傷:vWebb, et.al.: Am Rev R Dis 110:556-65, 1974vDreyfuss: Am Rev R Dis 148:1194-1203, 1993The aerated, ventral regions (baby lung)-Barotrauma 壓力傷的減輕壓力傷的減輕: Pneumothorax and emphysema, PIP 50 cmH2O u 吸氣平臺(tái)壓（吸氣平臺(tái)壓（IPP）：）：PEEP u 跨肺壓的意義更大跨肺壓的意義更大Volume, ml800600400200002040DPL02040Pao02040D

17、Pescm H2OLimitation of Plateau PressureHeterogenous InvolvementLung and Chest Wall Involvement2. 容量傷容量傷(Volutrauma）: Dreyfuss, 1988 (rats) , ARDS Network, 2000The aerated, ventral regions (baby lung)-VolutramavNEJM 2001;344:19866 cc/kg versus 12 cc/kg6 cc/kg versus 12 cc/kgv31% Mortality with small

18、tidal volumes (low plateau pressure)v38.9% Mortality in conventional tidal volume group (higher plateau pressures)332 patients without ARDS 12 ml/kg ALIARDS 17% 22 % 33% - Doctor induced ARDS 低潮氣量保護(hù)正常肺低潮氣量保護(hù)正常肺Development of ARDS and Tidal VolumevFor every 1cc/kg above 6cc/kg, vodds ratio of ALI inc

19、reased 1.33. 剪切傷剪切傷（Atelectrauma）: AtelectasisThe consolidation and atelectasisThe interface between the two areas-AtelectraumavAlveolar Collapsing-Reopening InjuryvZEEPvPEEPvAirwayvPressure100080060040020000 10 20 30 40Pressure, cm H2ONEJM 2001;344:19860 2 4 6Protective Ventilation6004002000Seconds

20、Volume, ml0 2 4 6Conventional Ventilation8006004002000Volume, mlAlveolaroverdistentionAlveolarcollapseGattinoni et al, AJRCCM 1998;158:3PEEP Effect: Influence of ARDS EtiologyPulmonary CauseNon Pulmonary Cause151050Change in Volume, LChange in Static Total Respiratory System Pressure, cm H2O04010302

21、000.80.41.21.6PEEP010203040 Best PEEP: CO, PaO2 , FiO2 FiO2 0.3 0.4 0.5 0.6-0.7 0.8-0.9 PEEP 5 5-8 8-10 10-12 14-18 NHLB ARDS clinical trials network, 2004, NEJM 549 patients, 28 days PEEP 8 vs. 13cmH2O, No differenceBest PEEPEffect of PEEP in ARDS Randomized 549 ARDS/ALI patients ARDS Network NEJM

22、2004; 351(4): 327 010203040500.00.70.80.91.0ProbabilityDays after Randomization50High PEEP13.2+3.5 cm H2O Low PEEP8.3+3.2 cm H2O High v Low PEEP - Age: 54 v 49 yr PO2/FiO2 151 v 165 PEEP not customized to pathophysiology Change in PO2 used to estimate recruitment - but may reflect change in cardiac

23、output rather than recruitmentRecruitment ManueverOpen lung and keep the lung open -Indication: Refractary hypoxmia -Contra-indication: Emphysema, PneumothoraxLow Percentage of Recruitable LungAirway Pressure, 5 cmH2OAirway Pressure, 45 cmH2OGattinoni et al, NEJM 2006;354:1775Percentage of Potential

24、ly Recruitable Lung* = 4%* Potentially Recruitable Lung = proportion of lung tissue in which aeration was restored when Paw increased from 5 to 45Higher Percentage of Recruitable LungAirway Pressure, 5 cmH2OAirway Pressure, 45 cmH2OGattinoni et al, NEJM 2006;354:1775Percentage of Potentially Recruit

25、able Lung* = 37%* Potentially Recruitable Lung = proportion of lung tissue in which aeration was restored when Paw increased from 5 to 45SuperimposedPressureOpeningPressureInflated0Alveolar Collapse(Reabsorption)20-60 cmH2OSmall AirwayCollapse10-20 cmH2OConsolidation New Ventilation StrategiesConven

26、tional Ventilation StrategyNormalize blood gases PaO2 PaCO2 pH New Ventilation StrategyLung Protective Strategy Support Respiration Minimizing Lung Injuryl Low tidal volume l Best PEEPl Permissive HypercapniaPermissive Hypercapnia Permissive hypercapnia: PaCO2 50-70mmHg, pH 7.15-7.25 Contra-indication: Heart Failure, Brain Inj