Acute-Lung-Injury-&-Acute-Respiratory-Distress-Syn.ppt

单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,Acute Lung Injury&Acute Respiratory Distress Syndrome,Translational,Evidence-BAsed Medicine,Xiangyu Zhang,MD,FCCP,ED&ICU,Shanghai Tenth Peoples Hospital,Shanghai Tongji University,Shanghai,China,DISCLOSURE,Techpool支持本次,学术讲座,Appreciate,Bench to Bedside,Translational medicine,Bench to Beside,Bedside to Bench,B2B,最初的描述，Definition,诊断,1、急性肺损伤(ALI),（1）急性起病。,（2）氧合指数PaO2/FiO2 300mmHg(与PEEP无关)。,（3）胸正位X光片示双侧浸润。,（4）肺动脉楔压Paw18mmHg或无左心房高压的临床依据。,2、ARDS,在上述ALI的基础上,PaO2/FiO2 200mmHg(与PEEP无关)。,1992年美欧ARDS专题会,诊断存在的问题,“Rapid onset”无法明确,与心源性肺水肿可能有交叉,病程的特征性没有临床资料,存在问题的原因,没有很好的、有效的或标准的沟通方式与机制,散发的特征导致数据没有积累,试验研究可能只局限于早期阶段（Max96hr）,病理学特征,Understand the lungUnderstand ARDS,抗凝治疗,雾化肝素/尿激酶治疗动物实验有效,雾化肝素治疗安全可行（CC2008）(Phase I,Austrilia),APC临床RCT结果受到质疑（N Engl J Med 2001,）（Severe Sepsis）（Prowess）,HETRASE 结果阴性（CCM 2009）（Severe Sepsis）,较多动物实验,短期效果阳性,糖皮质激素？,不可推荐ARDS常规使用激素,发病二周后使用可能有害,个体化病人与病情不同,很需要进一步研究,肺泡表面活性物质,实验研究有效,临床研究没有得到有效的结论,至今仍在研究阶段,06指南不推荐作为ARDS常规治疗,细胞因子抗体或拮抗剂,所有对ARDS和Sepsis的临床研究均为阴性结果,试图通过CRRT来减少炎症因子的研究也是阴性结果,选择性减少炎症因子的研究尚在进行中,吸入一氧化氮疗法，iNO,可以短期改善氧合,没有证明改善生存率,FDA没有批准,06指南不推荐,目前还在研究,iNO+PS实验证明效果很好,CHEST2009，MMP抑制剂,MMP抑制剂改善ALI,COL-3是四环素(Tetracycline)的化学修饰产物,不是抗生素,是抗炎药物,抗MMP,neutophil elastase,cytokines,COL-3动物实验（96h）有效,CHEST 2009,San Diego,Ongoing,Fish oil(omega-3 fatty acids),Anti-TF Antibody(ALT-836),Albumin and Starch Effects,Steroids in Patients With Early ARDS(,Italy,),methylene blue,+inhaled nitric oxide,(,Russian,),Sivelestat(弹性酶抑制药)(,Japan,),Albuterol(Beta-2受体激动剂),纠正低氧血症,机械通气,液相通气,体外膜肺(Extra-corporeal Membrane Oxygenator,ECMO),血管腔内氧合器(Intra-vascular Oxygenator,IVOX),Ventilation Strategies&BAL Cytokines,Tremblay,Valenza,Ribeiro,Li,Slutsky,J Clinical Investigation,99:944-52,1997,7,3,MVHP,15,10,HVZP,C,control,40,identical dV/dt,V,T,(cc/kg),PEEP,cm H,2,O,15,MVZP,100,200,1,200,1,400,*,C,MVHP,MVZP,HVZP,TNF-,a,pg/ml,50倍！,Ventilatory Strategy and BAL Cytokines,Tremblay,Valenza,Ribeiro,Li,Slutsky,J Clinical,Investigation,99:944-52,1997,*,p 0.05 vs.C,MVHP,MVZP,&,p 0.05 vs.C,MVHP,#,p 18,P/F75,Significant heart disease,SSC 2008,Crit Care Med 2008 Vol.36,No.1,SSC 2008,推荐对,ALI/ARDS,病人应用,6ml/kg,（预测体重）的目标潮气量。（,1B,）,推荐对,ALI/ARDS,病人进行平台压监测，对于被动通气的病人初始平台压目标设定在,30cmH,2,O;,检测平台压时应当考虑到胸廓的顺应性。（,1C,）,推荐对,ALI/ARDS,病人在必要降低平台压或减少潮气量时施行允许性高碳酸血症（,PaCO2,水平高于病前）。（,1C,）,SSC 2008,4.,推荐设定PEEP以阻止张开的肺在呼气末塌陷。（1C）,5.建议在有经验的单位，对于需要可能有害的FiO2和平台压的ALI/ARDS病人在没有不良后果高风险的条件下应用俯卧位通气。（2C）,6a.除非有禁忌，推荐机械通气的病人床头抬高减少误吸风险，防止呼吸机相关性肺炎。（1B）,6b.建议床头抬高3045.（2C）,7.建议无创通气（NIV）只能在少数轻中度低氧的、血流动力学稳定的、易于唤醒的、能够自我呼吸道保护的、能自主咳痰的、能很快恢复的ALI/ARDS病人考虑应用。,Crit Care Med 2007 Vol.35,No.1,Fernando Suarez-Sipmann,et al,Use of dynamic compliance for open lung positive end-expiratory pressure titration in an experimental study,Eight healthy pigs,Lung lavages,CT slices were obtained 2 cm cranial of the right diaphragmatic dome,Bobs new protocol,Patients,(n=549),ARDS/,ALI,P plat,(,cmH,2,O,),30,PEEP,(,cmH,2,O,),12.9 4,8.4,4,RR,(,b/min,),30,TV,(,ml/Kg,),6,The NIH randomized multicenter study assessing the effect on mortality of low vs high PEEP in ARDS,New Engl J Med 2004;351:327-336,NIH,PEEP selected according to a Table to achieve,minimal physiological oxygenation(88-95%),Patients,(,n=983,),ARDS/,ALI,P plat,(,cmH,2,O,),30,PEEP,(,cmH,2,O,),16.3 3,RR,(,b/min,),30,TV,(,ml/Kg,),6,9.1 4,The LOVS:Lung Open Ventilation Canadian Study,Canadian,Trial,Oxygenation was better in High PEEP,Compliance was better in High PEEP,Less rescue therapies in High PEEP,0,4,0,5,0,6,0,7,0,8,0,9,1,0,10,20,30,40,50,60,Days after randomization,Probability of survival,Low PEEP,High PEEP,PEEP selected according to a table to achieve,minimal physiological oxygenation+RM,Stewart T et al JAMA.2008;299(6):637-645,Patients,(,n=752,),ARDS/,ALI,P plat,(,cmH,2,O,),30,PEEP,(,cmH,2,O,),14.9 4,RR,(,b/min,),30,TV,(,ml/Kg,),6,7.4 4,French Trial,“Express”,PEEP selected to avoid overdistension or,to achieve maximal recruitment,PEEP set for PEEP tot 5-9 cmH2O,PEEP set for Plat 28-30 cmH2O,Oxygenation was better in Max distension,Higher ventilation free days in Max distension,Higher organ failure free days in Max distension,Mercat A et al JAMA.2008;299(6):646-655,The Express Study:randomized multicenter study assessing the effect on mortality of low vs high PEEP in ARDS,Brochard,2nd Sino-French Synposium of Critical Care Medcine,Shanghai,China,Brochard 2010:functional recruitment,用氧合方法在肺复张后设定PEEP的方法将受到质疑,N Engl J Med 2008;359:2095-104,Crit Care Med 2008;36:2980 2985,Dean Hess,et al.,阻抗断层扫描:EIT,Amato 2010,ARDSnet+LOVS+EXPRESS,Meta-analysis,Drive pressure is the key point,Cut off:16 cmH2O,Result:significant,Conclusion:,Drive pressure low is more important than Vt low.,Amato 2010,人的肺血管在背侧与腹侧分布不同,背侧血管分布多,背侧的血流不会因为俯卧位而减少,从而动摇了经典的West Band生理基础,食管压监测依据不足,循证医学,提出问题,寻找最好的证据,质量分五级,Meta,RCT,CT,病例系列，专家意见,严格评价证据的真实性与实用性,Systematic Review,Meta-analysis,应用证据指导医疗决策,对应用效果进行再评价（循证原则）,H1N1?,很需要积累本地的数据,国外的重症病例的特征不同（如：巴西Amato）,单个ICU的数据显然很分散,非常需要协作,ECMO,RM并非万能，对于严重的低氧血症，尤其是心脏功能很差的病人，ECMO可能是很有潜力的新疗法。,张翔宇，等。中国急救医学，2006；26（5）：398,