1、“围术期单肺与双肺通气的肺保护策略 ASA 2015 知识更新“读书报告,Perioperative Lung Protection Strategiesin One-lung and Two-lung Ventilation Peter Slinger, MD, FRCPC Department of Anesthesia University of Toronto and Toronto General Hospital Toronto, Ontario, Canada,提纲,1.COPD :呼吸驱动力、肺大泡、气流受限、auto-peep2、机械通气:ALI、VILI(呼吸机相关肺损伤)
2、3、围术期管理：外科相关因素、挥发性麻醉药在肺保护中的作用、超保护性肺通气(Ultraprotective Lung Ventilation)、液体和细胞外被、其它肺保护治疗4、总结,COPD,所有3期（FEV1 3049%预期值）及4期（FEV190% 12小时后，大潮气量组患者的支气管肺泡灌洗液炎症因子（TNF和 IL-8）显著升高.【18】Choi等比较了12ml/kg无PEEP VS 6ml/kg加用10cmH2O PEEP两种通气策略 5小时机械通气后，大潮气量组灌洗液显示促凝性改变。【19】一项纳入了150例无ALI危重患者随机对照研究将按预测体重给予10ml/kg VS 6ml/
3、kg两种潮气量的效果进行了对比 常规通气量组患者的血浆炎性因子显著升高。【20】,15. Gajic O, Dara SI, Mendez JL, et al.: Ventilator-associated lung injury in patients without acute lung injury at the onset of mechanical ventilation. Crit Care Med 2004; 32:181724.16. Gajic O, Frutos-Vivar F, Esteban A, Hubmayr RD, Anzueto A: Ventilator se
4、ttings as a risk factor for acute respiratory distress syndrome in mechanically ventilated atients. ntensive Care Med 2005; 31:92226.17. Michelet P, DJourno X-B, Roch A, et al.: Protective ventilation influences systemic inflammation after esophagectomy: A randomized controlled study. Anesthesiology
5、 2006; 105:91119.18. Pinheiro de Oliveira R, Hetzel MP, Silva M, Dallegrave D, Friedman G: Mechanical ventilation with high tidal volume induces inflammation in patients without lung disease. Crit Care 2010; 14:R39.19. Choi G, Wolthuis EK, Bresser P, et al.: Mechanical ventilation with lower tidal v
6、olumes and positive end-expiratory pressure prevents alveolar coagulation in patients without lung injury. Anesthesiology 2006; 105:68995.20. Determann R, Royakkers A, Wolthuis EK, et al.: Ventilation with lower tidal volumes as compared with conventional tidal volumes for patients without acute lun
7、g injury: A preventive andomized controlled trial. Crit Care 2010; 14:R1.,非伤害性或所谓保护性的通气设定仍可能使原本健康的肺形成肺损伤,小鼠 “单次打击”所致VILI模型进行的动物研究显示：即使是最小的伤害性肺通气设置仍可引起符合肺损伤的生化和组织病理学改变。【21】对啮齿动物模型进行机械通气的另一项研究显示：仅仅90分钟的保护性通气后就会出现显著的基因表达（包括参与免疫和炎症反应的基因）。这些改变是否对临床转归有影响，目前还不确定。【22】ALI是术后发生呼吸衰竭最常见的病因且与降低的术后生存率有关。【23】,21.
8、Wolthuis EK, Vlaar APJ, Choi G, et al.: Mechanical ventilation using non-injurious ventilation settings causes lung injury in the absence of pre-existing lung injury in healthy mice. Crit Care 2009; 13:R1.22. Ng CSH, Song Wan Ho AMH, Underwood MJ: Gene expression changes with a non-injurious ventila
9、tion strategy. Crit Care 2009; 13:40310.23. Fernandez-Perez ER, Sprung J, Alessa B, et al.: Intraoperative ventilator settings and acute lung injury after elective surgery: A nested case control study. Thorax 2009; 64:12127.,围术期肺损伤,围术期肺损伤,Q:ALI的主要危险因素？,Fernandez-Perez等，4000名患者，前瞻性病例对照研究，观察术中呼吸机设定与择期
10、手术后发生ALI的情况。研究显示：高危择期手术后ALI的发生率为3%。与对照组相比，发生ALI的患者术后生存率明显降低且住院时间延长。 有趣的是，ALI的发生与术中气道峰压有关，而与潮气量、PEEP或吸入氧浓度无关。一项特别观察危重患者发生ARDS的术中危险因素的回顾性队列研究发现：术中接受液体复苏大于20ml/kg/h的患者比接受液体复苏小于10ml/kg/h的患者发生ARDS的可能性高3倍（OR 3.1, 95% CI = 1.09.9, P = 0.05）。 在此项研究中，潮气量和血制品输注量与ARDS的发生无相关性，且大多数患者按理想体重设置潮气量为8-10ml/kg的通气，术中PEE
11、P为0。【24】,气道峰压？潮气量？PEEP？吸入氧浓度？液体量？输血？其他？,24.Hughes C, Weavind L, Banerjee A, et al.: Intraoperative risk factors for acute respiratory distress syndrome in critically ill patients Anesth Analg 2010; 111:46467.,SO:?,Recent studies have identified the use of large tidal volumes as a major risk factor f
12、or development of lung injury in mechanicallyventilated patients without ALI. Gajic et al.15reported that 25% of patients with normal lungs ventilated in an intensive care unit setting for 2 days or longer developed ALI or ARDS. The main risk factors for ALI were use of large tidal volumes, restrict
13、ive lung disease, and blood product transfusion. A prospective study from the same group found that tidal volumes higher than 700mL and peak airway pressures above 30 cm H2O were independently associated with the development of ARDS.16,Gajic等报道，约25%肺部正常的患者在ICU经历2天或更久的机械通气后发生了ALI或ARDS。【15】ALI的主要危险因素包
14、括：使用大潮气量、存在限制性肺部疾病以及输注血液制品。同一研究小组的一项前瞻性研究发现：潮气量700ml以及气道峰压30cmH2O是ARDS形成的独立危险因素。16,VILI,25. Lionetti V, Recchia FA, Ranieri VM: Overview of ventilator-induced lung injury mechanisms. Curr Opin Crit Care 2005; 11:826.,解释ALI/ARDS中见到的远隔器官发生功能障碍，优化通气策略在改善这种情况中的意义：,VILI至生物学创伤 持续加重肺损伤， 远隔器官发生功能障碍一项探讨VILI引
15、起远隔器官损伤新机制的研究显示：机械通气可引起肾脏及小肠的内皮细胞凋亡，并且同时伴有器官功能障碍的生化改变。【26】对小鼠进行的损伤性机械通气发现：肺泡牵拉诱发的粘性分子不只见于肺部，也可见于肝脏和肾脏。此外，机械通气后肺、肝、肾中细胞因子和趋化因子的表达伴随着粒细胞聚集的增加。【27】,26. Imai Y, Parodo J, Kajikawa O, et al.: Injurious mechanical ventilation and end-organ epithelial cell apoptosis and organ dysfunction in an experimental
16、 model of acute respiratory distress syndrome. JAMA 2003; 280:2104112.27. Hegeman MA, Henmus MP, Heijnen CJ, et al.: Ventilator-induced endothelial activation and inflammation in the lung and distal organs. Crit Care 2009; 13:R182.,术中呼吸机相关性肺损伤1、ARDS患者应用的肺保护性通气策略【28】是否适用于肺部健康患者的术中阶段？,一篇针对该问题的论文指出：目前仍
17、缺少关于术中最佳潮气量、PEEP和肺复张应用的随机对照研究。【29】尽管关于转归方面的研究不足，但基于我们对机械通气作用的认知，围术期目标性应用保护性肺通气策略似乎是合理的。三项【30-32】在腹部大手术患者中的随机对照研究显示了相互矛盾的结果。这些结果仍有待大规模研究来确认。,29. Beck-Schimmer B, Schimmer RC: Perioperative tidal volume and intraoperative open lung strategy in healthy lungs: Where are we going? Best Pract Res Clin Ana
18、esthesiol 2010; 24:199210.30. Treschan TA, KaisersW, Schafer MS, et al.: Ventilation with low tidal volumes during upper abdominal surgery does not improve postoperative lung function. Br J Anaesth 2012; 109:26371.31. Futier E, Constantin J-M, Paugam-Burtz C, et al.: A trial of intraoperative low ti
19、dal-volume in abdominal surgery. N Engl J Med 2013; 369:42836.32. Severgnini P, Selmo G, Lanza C, et al.: Protective mechanical ventilation during general anesthesia for open abdominal surgery improves postoperative pulmonary function. Anesthesiology 2013; 118:12547.,2、单肺？双肺？,一项在微创食管切除术中进行单肺通气的研究也发现
20、：小潮气量和PEEP可改善肺部转归。【34】单肺通气本身对通气侧和非通气侧肺均可造成损伤，【35】且这种损伤取决于单肺通气的时间长短。【36】因此最好要避免传统的单肺通气模式，而尽可能对非通气肺应用连续气道正压（CPAP）。【37】这在不涉及肺的微创胸内手术（如心血管、食道手术）中是一个特别值得注意的选择。,34. Shen Y, Zhong M, Wu W, et al.: The impact of tidal volume on pulmonary complications following minimally invasive esophagectomy. J Thorac Car
21、diovasc Surg 2013; 146:126773.35. Kozian A, Schilling T, Freden F, et al.: One-lung ventilation induces hyperperfusion and alveolar damage in the ventilated lung. Br J Anaesth 2008; 00:54959.36. Tekinbas C, Ulusoy H, Yulug E, et al.: One-lung ventilation: For how long? J Cardiothorac Vasc Surg 2007;
22、 134:40510. 37. Verhage RJ, Boone J, Rijkers GT, et al.: Reduced local immune response with continuous positive airway pressure during one-lung ventilation for sophagectomy. Br J Anaesth 2014; 112: 9208.,3、过量补液？大潮气量？,传统观点经常把肺切除后肺损伤的发生归咎于手术中麻醉医师的过量补液。现有证据表明：相比过量补液，ALI可能与单肺通气中过度应用大潮气量更具相关性。【38】目前尚缺少在人
23、身上应用小VT/大VT进行单肺通气的具有说服力的前瞻性研究，但已有大型动物研究。,38. Slinger P: Postpneumonectomy pulmonary edema: Good news, bad news. Anesthesiology 2006; 105:25.39. Kuzkov V, Subarov E, Kirov M, et al.: Extravascular lung water after pneumonectomy and one-lung ventilation in sheep. Crit Care Med 2007; 35:15509.,围术期管理1、外
24、科相关因素,手术部位是肺部发生并发症的一个重要预测指标，其中上腹部、胸部切口（任何接近靠近膈肌的切口）影响最大。【40】与开放式手术相比，大型体腔手术时如果使用微创技术可减少肺部并发症的发生。【41-42】肺不张作为一种可引起肺损伤的病理状态，经常发生于开放手术后及高达90%的全麻患者中。【43】存在争议，回顾【45，46】与前瞻性【47】研究均显示合适的胸段硬膜外镇痛能减少腹部大手术及胸部手术后呼吸并发症（肺不张、肺炎以及呼衰）的发生。硬膜外镇痛的获益程度似乎与患者潜在肺部疾病的严重程度直接成正比，如合并COPD的患者看起来是从硬膜外镇痛中获益最多的。【48】尚未对高危患者进行特别的研究，但
25、是通过对胸外科手术患者应用椎旁阻滞和硬膜外镇痛进行比较显示：椎旁阻滞与硬膜外镇痛效果相当，而椎旁阻滞副作用和并发症更少。【49，50】对于腹部大手术后出现早期氧饱和度下降的患者，术后阶段积极进行物理治疗并结合应用CPAP可降低严重呼吸并发症的发生。【51】,40. Smetana GW: Postoperative pulmonary complications: An update on risk assessment and reduction. Cleve Clin J Med 2009; 76: S605.41. Weller WE, Rosati C: Comparing outco
26、mes of laparoscopic versus open bariatric surgery. Ann Surg 2008; 248:1015.42. Ramivohan SM, Kaman L, Jindal R, Singh R, Jindal SK: Postoperative pulmonary function in laparoscopic versus open cholecystectomy: Prospective, comparative study. Indian J Gastroenterol 2005; 24:68.43. Duggan M, Kavanagh
27、B: Pulmonary atelectasis: A pathogenic perioperative entity. Anesthesiology 2005; 102:83454.44. Tusman G, Bohm SH, Suarez-Shipman F: Alveolar recruitment improves ventilatory efficiency of the lungs during anesthesia. Can J Anaesth 2004; 51:7237.45. Ballantyne JC, Carr DB, de Ferranti S: The compara
28、tive effects of postoperative analgesic therapies on pulmonary outcome: Cumulative meta-analysis of randomized, controlled trials. Anesth Analg 1998; 86:598612.46. Liu SS, Wu CL: Effect of postoperative analgesia on major postoperative complications: A systematic update of the evidence. Anesth Analg
29、 2007; 3:689702.47. Rigg J, Jamrozik K, Myles P, et al.: Epidural anaesthesia and analgesia and outcome after major surgery: A randomized trial. Lancet 2002; 359:127682.48. Licker MJ, Widikker I, Robert J, et al.: Operative mortality and respiratory complications after lung resection for cancer: Imp
30、act of chronic obstructive pulmonary disease and time trends. Ann Thorac Surg 2006; 81:18308.49. Scarci M, Joshi A, Attia R: In patients undergoing thoracic surgery is paravertebral block as effective as epidural analgesia for pain management. Interact Cardiovasc Thorac Surg 2010; 10:926.50. Davies
31、RG, Myles PS, Graham JM: A comparison of the analgesic efficacy and side effects of paravertebral vs. epidural blockade for thoracotomyA systematic review and meta-analysis of randomized trials. Br J Anaesth 2006; 96:41826.51. Squadrone V, Coha M, Cerutti E, et al.: Continuous positive airway pressu
32、re for the treatment of postoperative hypoxemia: A randomized controlled trial. JAMA 2005; 293:58995.,2、挥发性麻醉药在肺保护中的作用,挥发性麻醉药具有免疫调节功能。近期对单肺通气中ALI模型及肺缺血再灌注损伤病例的研究显示：挥发性麻醉药可以作为预处理或后处理药物通过抑制促炎调节因子的表达来实现肺保护作用【52】。对内毒素介导的动物ALI模型进行异氟醚预处理，多型核白细胞集聚及微血管蛋白漏出的减少证明预处理产生了保护作用。【53】对活体大鼠ALI模型进行七氟醚后处理减轻了肺损伤的程度并保护了肺
33、功能。【54】在一项前瞻性研究中，应用单肺通气接受胸外科手术的患者被随机分为丙泊酚组和七氟醚组。通过比较非通气侧的肺部炎症标志物水平，研究者发现七氟醚组患者具有较轻的炎症反应。【55】值得注意的是，七氟醚组患者有更好的临床转归且总体不良事件发生率明显更低。【56】一项比较了单肺通气中分别应用地氟醚和丙泊酚麻醉并检测了通气侧肺部炎症反应的研究表明：地氟醚组患者的炎症标志物如IL-8, IL-10, PMN elastase和TNF均明显更低。 现有结果确实已经指明：无论是在损伤前、损伤中、还是损伤后应用，挥发性麻醉药都具有减轻发生在肺部和受损器官的促炎症反应的作用。,52. Fujinaga T
34、, Nakamura T, Fukuse T, et al.: Isoflurane inhalation after circulatory arrest protects against warm ischemia reperfusion injury of the lungs. Transplantation 2006; 82:116874.53. Reutershan J, Chang D, Hayes JK, Ley K: Protective effects of isoflurane pretreatment in endotoxin-induced lung injury. A
35、nesthesiology 2006; 104:5117.54. Voigtsberger S, Lachmann RA, Leutert AC, et al.: Sevoflurane ameliorates gas exchange and attenuates lung damage in experimental lipopolysaccharide-induced lung injury. Anesthesiology 2009; 111:123848.55. De Conno E, Steurer MP, Wittlinger M, et al.: Anesthetic-induc
36、ed improvement of the inflammatory response to one-lung ventilation. Anesthesiology 2009; 110:131626.56. Schilling T, Kozian A, KretzschmarM, et al.: Effects of propofol and desflurane anaesthesia on the alveolar inflammatory response to onelung ventilation. Br J Anaesth 2007; 99:36875.,3、超保护性肺通气(Ul
37、traprotective Lung Ventilation),概念：由ALI/ARDS中的保护性肺通气发展而来，应用体外肺支持装置以及近似静止通气（near-static ventilation）策略。57ARDSNet及动物研究数据显示更小的潮气量（3ml/kg，相比6-12ml/kg）可显著减轻内皮细胞和上皮细胞损伤。58,59换言之，“保护性”潮气量仍可诱发VILI，而应用更小潮气量时，存在二氧化碳清除和氧合的问题。Novalung:一种无泵装置，可在显著减少分钟通气量的同时纠正PaCO2和pH。一项使用Novalung（潮气量2.2ml/kg，呼吸频率每分钟6次）进行通气的肺切除后A
38、RDS的动物模型研究显示：与传统的肺保护性通气策略相比，Novalung可明显改善患者的转归。60一系列不同病情的人类病例报道结果：Novalung使潮气量不高于3 mL/kg、低吸气平台压、高PEEP以及低呼吸频率通气都成为可能，这减少了VILI和继发性远隔器官衰竭的发生。61一项对严重ARDS患者进行的随机研究显示：与应用常规通气策略的患者生存率（47%）相比，应用有泵的ECMO结合保护性肺通气可明显增加患者的生存率（达63%）。62,57. The Cardiothoracic Surgery Network website. Available at: www.CTSNet.org.
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40、ume reduces epithelial and endothelial injury in acid-injured rat lungs. AmJ Respir Crit Care Med 2002; 165:2429.60. Iglesias M, Jungebluth P, Petit C, et al.: Extracorporeal lung membrane provides better lung protection than conventional treatment for severe stpneumonectomy noncardiogenic acute res
41、piratory distress syndrome. J Thorac Cardiovasc Surg 2008; 6:136271.61. Mallick A, Elliot S, McKinlay J, BodenhamA: Extracorporeal carbon dioxide removal using the Novalung in a patient with intracranial bleeding. Anaesthesia 2007; 62:724.62. Peek GJ, Mugford M, Tiruvoipati R, et al.: Efficacy and economic assessment of conventional ventilatory support versus extracorporeal membrane oxygenation for severe adult respiratory failure (CESAR): Amulticentre randomised controlled trial. Lancet 2009; 374:135163.,
