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（Ventilator induced lung injury, VILI) (Ventilator associated lung injury, VALI),中山大学附属第一医院,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%,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）,Inflammation Hemorrhage Edema Fibrosis Pulmonary dysfunction Systemic effects,机械通气导致了怎样的肺损伤？,1. B. Ouyang（欧阳彬), Jafari, O. Syrkina, C.A. Hales and D.A. Quinn. N-acetyl-L-cysteine inhibited TGF- production and reduced lung collagen formation in ventilator-induced lung injury. FASEB Journal. 2004 Mar: 18(4): 218.11 (A323). 2. Bin Ouyang（欧阳彬), 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（欧阳彬）, Deborah A. Quinn, and Charles A. Hales. 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（欧阳彬）, Choukroun G, Matyal R, Mascarenhas M, Jafari B, Bonyentre JV, Force T and Quinn DA. Stretch-induced IL-8 depends on c-Jun NH2-terminal and nuclear factor-kappaB inducing kinases. Am J Physiol Lung Cell Mol Physiol. 2003 Aug; 285(2): L464-75. 5 Jafari B, Ouyang B（欧阳彬）, 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): 43-53. 6. B. Jafari, B. Ouyang（欧阳彬), 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（欧阳彬）, Deborah A. Quinn. Stretch-Induced IL-8 is Dependent on c-Jun N-Terminal Kinase and Nuclear Factor-B-Inducing Kinase Pathways ATS 2003, C112. 8. Li-Fu Li, Bin Ouyang（欧阳彬）, 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 9. Quinn DA, Jafari B, Li LF, Mascarenhas M, Ouyang B（欧阳彬）, 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. Mascarenhas MM, Day RM, Ochoa CD, Choi WI, Yu L, Ouyang B（欧阳彬）, 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：我的体会,Ventilator,RatMousePigSheep,1. 炎症（Inflammation）,Tidal Volume 3 ml/kg,Tidal Volume 6 ml/kg,Tidal Volume 12 ml/kg,Tidal Volume 12 ml/kg,2003, J. Am Physio. Lung,Tidal Volume 7 ml/kg for 2hrs,Tidal Volume 20 ml/kg for 2hrs,2. 出血（Hemorrhage）,3. 水肿（Edema）,Protein Leakage,Water Leakage,2003, Am J. Respir. CCM,VT 20,VT 7,4. 肺纤维化（Lung Fibrosis）,2003, ATS, Seattle,- VILI MODEL OF RATS,肺纤维化 （Lung Fibrosis）,* p 0.05 vs. Collagen(Static) p 0.05 vs. TGF-b1(Static),*,Static 0.5 hour 1 hour 4 hour,Stretch,Collagen (ug/ml),*,TG F-b1 (pg/ml),Collagen,TGF-b1,120,100,80,60,20,40,120,100,80,60,20,40,Study in Fibroblasts,2004, FASEB Journal,PaO2 (mmHg),PCO2 (mmHg),pHa,7.457.407.357.307.25,75,100,Non-MV,2 hour,2nd day,3rd day,4th day,Time of lung tissue harvested (after 2 hour MV),25,50,75,125,*,* p 0.05 vs. VT 7,VT 7,VT 20,*,*,5. 肺功能障碍（Pulmonary Dysfunction）,2002, Appl. J. Physio,6. 全身效应（Systemic Effects）,2003, Am J. Respir. CCM,- Proteinuria,Static cells,Stretched cells,Systemic Effects,2005, MJCLA,- Anti-inflammatory cytokine,TGFb1 and TGFb2 up-regulation found in rat serum of VILI,*,*,#,* p 0.05 vs Vt 7ml/kg# p 50 cmH2O 容量伤（Volutrauma）: Dreyfuss, 1988 (rats) , ARDS Network, 2000 剪切伤（Atelectrauma）: Atelectasis 生物伤（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,呼吸机相关性肺损伤,BarotraumaPneumothorax and emphysema, PIP 50 cmH2O,1. 压力伤:,Webb, et.al.: Am Rev R Dis 110:556-65, 1974,Dreyfuss: Am Rev R Dis 148:1194-1203, 1993,The aerated, ventral regions (baby lung)-Barotrauma,压力伤的减轻: Pneumothorax and emphysema, PIP 50 cmH2O 吸气平台压（IPP）：PEEP 跨肺压的意义更大,Volume, ml,800,600,400,200,0,0,20,40,DPL,0,20,40,Pao,0,20,40,DPes,cm H2O,Limitation of Plateau Pressure,Heterogenous Involvement,Lung and Chest Wall Involvement,2. 容量伤(Volutrauma）: Dreyfuss, 1988 (rats) , ARDS Network, 2000,The aerated, ventral regions (baby lung)-Volutrama,NEJM 2001;344:1986,6 cc/kg versus 12 cc/kg,6 cc/kg versus 12 cc/kg,31% Mortality with small tidal volumes (low plateau pressure)38.9% Mortality in conventional tidal volume group (higher plateau pressures),332 patients without ARDS 12 ml/kg ALIARDS 17% 22 % 33% - Doctor induced ARDS,低潮气量保护正常肺,Development of ARDS and Tidal Volume,For every 1cc/kg above 6cc/kg, odds ratio of ALI increased 1.3,3. 剪切伤（Atelectrauma）: Atelectasis,The consolidation and atelectasis,The interface between the two areas-Atelectrauma,Alveolar Collapsing-Reopening Injury,ZEEP,PEEP,AirwayPressure,10008006004002000,0 10 20 30 40,Pressure, cm H2O,NEJM 2001;344:1986,Volume, ml,Gattinoni et al, AJRCCM 1998;158:3,PEEP Effect: Influence of ARDS Etiology,Pulmonary Cause,Non Pulmonary Cause,15,10,5,0,Change in Volume, L,Change in Static Total Respiratory System Pressure, cm H2O,0,40,10,30,20,0,0.8,0.4,1.2,1.6,PEEP,0,10,20,30,40,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 difference,Best PEEP,Effect of PEEP in ARDS Randomized 549 ARDS/ALI patients,ARDS Network NEJM 2004; 351(4): 327,0,10,20,30,40,50,0.0,0.7,0.8,0.9,1.0,Probability,Days after Randomization,50,High 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,Recruitment Manuever,Open lung and keep the lung open -Indication: Refractary hypoxmia -Contra-indication: Emphysema, Pneumothorax,Low Percentage of Recruitable Lung,Airway Pressure, 5 cmH2O,Airway Pressure, 45 cmH2O,Gattinoni et al, NEJM 2006;354:1775,Percentage of Potentially Recruitable Lung* = 4%,* Potentially Recruitable Lung = proportion of lung tissue in which aeration was restored when Paw increased from 5 to 45,Higher Percentage of Recruitable Lung,Airway Pressure, 5 cmH2O,Airway Pressure, 45 cmH2O,Gattinoni et al, NEJM 2006;354:1775,Percentage of Potentially Recruitable Lung* = 37%,* Potentially Recruitable Lung = proportion of lung tissue in which aeration was restored when Paw increased from 5 to 45,Superimposed,Pressure,New Ventilation Strategies,Conventional Ventilation Strategy,Normalize blood gases PaO2 PaCO2 pH,New Ventilation Strategy,Lung Protective Strategy Support Respiration Minimizing Lung Injury,Low tidal volume Best PEEP Permissive Hypercapnia,Permissive Hypercapnia,Permissive hypercapnia: PaCO2 50-70mmHg, pH 7.15-7.25 Contra-indication: Heart Failure, Brain Injury or brain operation,PlP W/D Pro. PaO2 Cells Injury scorePaCO2: 40mmHg 27 9.7 1350 165 6.86 7PaCO2: 80-100m