Acute Lung Injury & Acute Respiratory Distress Syndrome Translational, Evidence-BAsed Medicine Xiangyu Zhang, MD, FCCP ED & ICU Shanghai Tenth People’s 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 最初的描述，Definition 病理学特征诊断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Paw≤18mmHg 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)。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 ）病理学特征炎症凝血？？？Sepsis DIC Understand the lung Understand 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干预：肺泡水转运（AFC ）AFC 增加与生存率改善相关AFC 增加与通透性降低相关ENaC 对生存是必须的水通道并不影响AFC Beta-2 激动剂可促进AFC 临床有效性目前较多研究糖皮质激素？？？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中华医学会重症医学分会ALI/ARDS 指南2006 ALI/ARDS 早期没有预防作用没有治疗作用对过敏性的ARDS 有效ARDS 纤维化期不能降低死亡率明显改善氧合明显改善肺顺应性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Shanghai 2009, 12 Centers 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) MARCELO AMATO, M.D.,et al. (N Engl J Med 1998;338:347-54.) EFFECT OF A PROTECTIVE-VENTILATION STRATEGY ON MORTALITY IN THE ACUTE RESPIRATORY DISTRESS SYNDROME MARCELO AMATO, M.D.,et al. (N Engl J Med 1998;338:347-54.) Burkhard Lachmann 2007 年秋，南京，Lecture & workshop RM with PCV PCV: 60 cmH2O—3 次PEEP: 15 cmH2O 然后：逐步调定PEEP, PIP 可以重复RM 目标：驱动压（PIP-PEEP ）尽量小保持最低氧供要求允许性高碳酸血症高频通气（HFOV ）利用高频振荡通气（HFOV ）施行肺保护TOOLS Orlando, Jeminez Treatment with Oscillation and an Open Lung strategy (TOOLS) Crit Care Med 2005; 33(3): 479 Multi-center: Toronto, Paris, Cardiff ，Boston Ferguson, Kacmarek, Slutsky, et al. New protocol with HFOV and RM 25 patients with early ARDS Inclusion: Age>18, P/F<200mmHg, ……Exclusion: Age>75, Significant heart disease, ……Brochard 2nd Sino-French Synposium of Critical Care Medcine Shanghai, China Brochard 2010: functional recruitment 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。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≤30cmH2O; 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30 ～45o. （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 Bob’s new protocol Patients ( n=549 ) ARDS/ ALI P plat (cmH2O) < 30 PEEP (cmH2O) 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 (cmH2O) < 30 PEEP (cmH2O) 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 (cmH2O) < 30 PEEP (cmH2O) 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 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. www.book118.com.cn www.book118.com.cn * 1992 年美欧ARDS 专题会CROSS TALK??? 消耗性凝血病12 个ICU ，48 例严重脓毒症与脓毒性休克非干预性临床调查12/48 例由于各种原因应用了肝素或低分子肝素Arthur S Slutsky ：VILI 与肺保护机械通气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 VT (cc/kg) PEEP cm H2O 15 MVZP 100 200 1,200 1,400 * § § C MVHP MVZP HVZP T NF-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 < 0.05 vs. C Cytokines in Humans Stuber et al Int Care Med 2002;28:834-841 JAMA 289:2104-2112,2003 Systemic Effects of VILI Imai et al JAMA 289:2104-2112,2003 Biophysical Injury shear overdistention cyclic stretch D intrathoracic pressure alveolar-capillary permeability cardiac output organ perfusion Biochemical Injury (Biotrauma) mf cytokines, complement, PGs, LTs, ROS, proteases bacteria Epithelium/ interstitium neutrophils Distal Organ Dysfunction Mechanical Ventilation Slutsky, Tremblay Am J Resp Crit Care Med. 1998;157:1721-5 DEATH EFFECT OF A PROTECTIVE-VENTILATION STRATEGY ON MORTALITY IN THE ACUTE RESPIRATORY DISTRESS SYNDROME * EXPRESS_RESULTS_230806_SURVIE Graph1 t Maximal recruitment Minimal distension .00 .00 .00 .00 .00 .00 .00 .00 .00 .00 .00 .00 .00 .00 .00 .00 .00 .00 .00 .00 .00 .00 .00 .00 .00 .00 .00 .00 .00 .00 .00 .00 .00 .00 .00 .00 .00 .00 .00 .00 .00 .00 .00 .00 .00 .00 .00 .00 .00 .00 .00 .00 .00 .00 .00
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