普胸外科围手术期肺保护研究
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摘要
呼吸衰竭是需要单肺通气的普胸外科(包括肺叶切除术和食管癌切除术等)术后最常见并发症,ARDS/ALI是引起呼吸衰竭的重要病因,死亡率超过50%。文献报道,肺叶切除术后ARDS/ALI发生率为0.9%-3.7%,食管癌切除术后发生率为10-20%。ARDS/ALI机制尚不完全清楚,手术创伤导致的炎症因子释放、肠源性内毒素吸收是可能的原因,而OLV则是术后ARDS/ALI另一重要原因。单肺通气时,非重力依赖侧肺萎陷,手术结束后肺再次复张可能会产生复张性肺损伤。若之前存在气胸、胸腔积液、肿瘤压迫等病理因素导致的长时间肺不张,在肺快速复张后可能会产生严重的复张性肺水肿。另一方面,在重力依赖侧,通气的单肺承受了相对更大的潮气量,肺泡被过度牵拉,可能导致机械通气相关性肺损伤。我们分别对非重力依赖侧和重力依赖侧在OLV时采取相应的保护性措施,使得两侧肺承受更小的损伤,以降低术后ARDs/ALI的发生率。
第一部分褪黑素对复张性肺水肿的保护作用
[目的]肺不张后快速复张会产生复张性肺水肿(reexpansion pulmonary edema, RPE),本实验旨在研究褪黑素对复张性肺水肿是否存在保护作用。[方法]我们通过夹闭大鼠左主支气管造成左肺不张,48小时后在开放左主支气管使得左肺复张以建立复张性肺水肿模型。在肺复张前30分钟我们分别腹腔注射melatonin(10mg/kg)和溶媒安慰剂,比较两组复张后的肺组织湿干比、氧合指数PaO2/FiO2、和肺组织中NO、MPO、MDA、IL-8含量的差异。[结果]通行检测我们发现,melatonin组大鼠复张后肺组织的湿／干比显著低于溶媒组,动脉血氧合指数PaO2/FiO2高于溶媒组,肺组织匀浆中NO、MPO、MDA和IL-8浓度均低于溶媒组。HE染色显示melatonin组肺组织水肿程度较轻、炎症细胞侵润较少。
[结论]由此我们推断melatonin通过减少肺复张后的氧化性损伤,抑制炎症细胞的侵润,达到减轻肺水肿、改善肺部氧合的作用。
第二部分单肺通气时保护性通气策略对术后肺损伤的影响的临床试验
[目的]单肺通气时相对大潮气量会引起重力依赖侧肺的损伤,本试验旨在探究单肺通气时小潮气量是否能减轻术后肺损伤的程度。[方法]我们选择择期食管癌切除术的病人,随机分成OLV保护性同期策略组和常规通气策略组。保护性同期策略组病人在OLV时采用5ml/kg的潮气量和5cmH2O水平的PEEP,常规同期策略组采用8ml/kg的潮气量和0cmH2OPEEP。在术前和术毕即刻我们收集病人通气侧肺的肺泡灌洗液检测TNF-à、IL-1β、IL-6和IL-8浓度、术后18小时氧合指数、肺部CT扫描结果以及并发症发生率。[结果]试验结果显示,保护性通气策略组术后肺泡灌洗液中IL-1β和IL-8浓度明显低于常规通气策略组,术后18小时氧合指数PV组显著高于CV组,术后并发症发生率PV组低于CV组,但差异无统计学意义。[结论]该试验提示保护性通气策略可以减少0LV时炎症因子的释放,改善术后氧合能力。虽然PV组术后ARDS/ALI发生率和其他并发症的发生率低于CV组,但差异无显著性,这可能与本试验的样本量较小有关,今后可深入研究,扩大样本量,找出相关的差异性。
Respiratory failure is the most common complication after thoracic surgery (including pneumonectomy and esophagectomy) which needs one lung ventilation. ARDS/ALI is an important cause of postoperative respiratory failure with the mortality rate over 50%. Literatures show that ARDS/ALI occurs in 0.9%-3.75% of cases after pneumonectomy and incident rate in esophagectomy cases ranges from 10% to 20%. The mechanism of ARDS is unknown, and the release of inflammatory mediators and gut-related endotoxins may be the cause.Furthermore, OLV is another crucial cause of postoperative ARDS/ALI. During one lung ventilation, the nondependent lung collapses and then is sequentially reexpanded at the end of operation, which may cause reexpansion lung injury. If there is pneumothorax, pleural effusion or tumor pressing lungs before surgery which leads to long term atelectasis, rapid reexpansion of the lung can cause severe reexpansion pulmonary edema. On the other hand, ventilated dependent lung endure relative bigger tidal volume and alveolar is overstretched that can lead to ventilator induced lung injury. We apply protective methods respectively to nondependent lung and dependent lung during OLV to prevent both lungs from injuries, by which we can reduce the incident rate of postoperative ARDS/ALI.
Part One:The protective effect of melatonin on reexpansion pulmonary edema.
Objective
Rapid reexpansion of collapsed lung will lead to reexpansion pulmonary edema. The experiment was to investigate whether melatonin could prevent expanded lung from reexpansion injury.
Method We collapsed left lungs of rats by ligating the left bronchus with silk, and then reexpanded left lungs after 48 hours to achieve animal mode of reexpansion pulmonary edema.30 minutes before reexpansion we injected melatonin (10mg/kg) or vehicle placebo intraperitoneally. We compared Wet/Dry Ratio, Oxygenation Index and NO, MPO, MDA and IL-8 levels of reexpanded lungs between two groups.
Results
We found that wet/dry ratio of melatonin group was significantly lower than vehicle group, and oxygen index (PaO2/FiO2) of melatonin was higher than vehicle group.
The levels of NO, MPO, MDA and IL-8 of lung homogenate were lower in melatonin group than those in vehicle group. Hematoxylin and eosin stain of reexpanded lungs showed that melatonin-pretreated lungs had less pulmonary edema level and less inflammatory cells infiltrating.
Conclusion
Hence we speculated that melatonin lessen pulmonary edema and improve oxygenation after reexpansion by attenuating oxidative stress and inhibiting leukocytes infiltration.
Part Two:The impact of protective ventilation strategy during OLV on postoperative ALI:a prospective randomized control trial
Objective
Relatively large tidal volume during one lung ventilation(OLV) can cause injury of dependent lung. The trial was to investigate whether low tidal volume ventilation during OLV could attenuate postoperative lung injury.
Method
The patients for selective esophagectomy were randomly assigned to two groups: Pretective Ventilation Group(Group PV) and Conventional Ventilation Group(Group CV). Patients of Group PV were ventilated with tidal volume of 5ml/kg and 5 cmH2O PEEP, and patients of Group CV were ventilated with tidal volume of 8ml/kg and zero PEEP. We collected bronchial lavage fluid of all patients before surgery and at the end of operation to detect TNF-α,IL-1β,IL-6 and IL-8 level in BALF. And Oxygenation Index, postoperative CT scan of lungs as well as incidence rate of complications were collected.
Results
The results showed that IL-1 and IL-8 levels in BALF of Group PV were significantly lower than that of Group CV. Oxygenation Index of was significantly higher in patients of Group PV. Cases with postoperative complications in Group PV was less than that in Group CV, but that difference was not significant.
Conclusion
The trial suggested that protective ventilation strategy could attenuate release of cytokines and improve postoperative oxygenation capacity. Maybe the sample size of this trial was relatively small to detect the difference of incident rate of ARDS/ALI and other complications between two groups, so we would carry out a further tiral with a large sample capacity to fix the problem.
第一部分褪黑素对复张性肺水肿的保护作用
[目的]肺不张后快速复张会产生复张性肺水肿(reexpansion pulmonary edema, RPE),本实验旨在研究褪黑素对复张性肺水肿是否存在保护作用。[方法]我们通过夹闭大鼠左主支气管造成左肺不张,48小时后在开放左主支气管使得左肺复张以建立复张性肺水肿模型。在肺复张前30分钟我们分别腹腔注射melatonin(10mg/kg)和溶媒安慰剂,比较两组复张后的肺组织湿干比、氧合指数PaO2/FiO2、和肺组织中NO、MPO、MDA、IL-8含量的差异。[结果]通行检测我们发现,melatonin组大鼠复张后肺组织的湿／干比显著低于溶媒组,动脉血氧合指数PaO2/FiO2高于溶媒组,肺组织匀浆中NO、MPO、MDA和IL-8浓度均低于溶媒组。HE染色显示melatonin组肺组织水肿程度较轻、炎症细胞侵润较少。
[结论]由此我们推断melatonin通过减少肺复张后的氧化性损伤,抑制炎症细胞的侵润,达到减轻肺水肿、改善肺部氧合的作用。
第二部分单肺通气时保护性通气策略对术后肺损伤的影响的临床试验
[目的]单肺通气时相对大潮气量会引起重力依赖侧肺的损伤,本试验旨在探究单肺通气时小潮气量是否能减轻术后肺损伤的程度。[方法]我们选择择期食管癌切除术的病人,随机分成OLV保护性同期策略组和常规通气策略组。保护性同期策略组病人在OLV时采用5ml/kg的潮气量和5cmH2O水平的PEEP,常规同期策略组采用8ml/kg的潮气量和0cmH2OPEEP。在术前和术毕即刻我们收集病人通气侧肺的肺泡灌洗液检测TNF-à、IL-1β、IL-6和IL-8浓度、术后18小时氧合指数、肺部CT扫描结果以及并发症发生率。[结果]试验结果显示,保护性通气策略组术后肺泡灌洗液中IL-1β和IL-8浓度明显低于常规通气策略组,术后18小时氧合指数PV组显著高于CV组,术后并发症发生率PV组低于CV组,但差异无统计学意义。[结论]该试验提示保护性通气策略可以减少0LV时炎症因子的释放,改善术后氧合能力。虽然PV组术后ARDS/ALI发生率和其他并发症的发生率低于CV组,但差异无显著性,这可能与本试验的样本量较小有关,今后可深入研究,扩大样本量,找出相关的差异性。
Respiratory failure is the most common complication after thoracic surgery (including pneumonectomy and esophagectomy) which needs one lung ventilation. ARDS/ALI is an important cause of postoperative respiratory failure with the mortality rate over 50%. Literatures show that ARDS/ALI occurs in 0.9%-3.75% of cases after pneumonectomy and incident rate in esophagectomy cases ranges from 10% to 20%. The mechanism of ARDS is unknown, and the release of inflammatory mediators and gut-related endotoxins may be the cause.Furthermore, OLV is another crucial cause of postoperative ARDS/ALI. During one lung ventilation, the nondependent lung collapses and then is sequentially reexpanded at the end of operation, which may cause reexpansion lung injury. If there is pneumothorax, pleural effusion or tumor pressing lungs before surgery which leads to long term atelectasis, rapid reexpansion of the lung can cause severe reexpansion pulmonary edema. On the other hand, ventilated dependent lung endure relative bigger tidal volume and alveolar is overstretched that can lead to ventilator induced lung injury. We apply protective methods respectively to nondependent lung and dependent lung during OLV to prevent both lungs from injuries, by which we can reduce the incident rate of postoperative ARDS/ALI.
Part One:The protective effect of melatonin on reexpansion pulmonary edema.
Objective
Rapid reexpansion of collapsed lung will lead to reexpansion pulmonary edema. The experiment was to investigate whether melatonin could prevent expanded lung from reexpansion injury.
Method We collapsed left lungs of rats by ligating the left bronchus with silk, and then reexpanded left lungs after 48 hours to achieve animal mode of reexpansion pulmonary edema.30 minutes before reexpansion we injected melatonin (10mg/kg) or vehicle placebo intraperitoneally. We compared Wet/Dry Ratio, Oxygenation Index and NO, MPO, MDA and IL-8 levels of reexpanded lungs between two groups.
Results
We found that wet/dry ratio of melatonin group was significantly lower than vehicle group, and oxygen index (PaO2/FiO2) of melatonin was higher than vehicle group.
The levels of NO, MPO, MDA and IL-8 of lung homogenate were lower in melatonin group than those in vehicle group. Hematoxylin and eosin stain of reexpanded lungs showed that melatonin-pretreated lungs had less pulmonary edema level and less inflammatory cells infiltrating.
Conclusion
Hence we speculated that melatonin lessen pulmonary edema and improve oxygenation after reexpansion by attenuating oxidative stress and inhibiting leukocytes infiltration.
Part Two:The impact of protective ventilation strategy during OLV on postoperative ALI:a prospective randomized control trial
Objective
Relatively large tidal volume during one lung ventilation(OLV) can cause injury of dependent lung. The trial was to investigate whether low tidal volume ventilation during OLV could attenuate postoperative lung injury.
Method
The patients for selective esophagectomy were randomly assigned to two groups: Pretective Ventilation Group(Group PV) and Conventional Ventilation Group(Group CV). Patients of Group PV were ventilated with tidal volume of 5ml/kg and 5 cmH2O PEEP, and patients of Group CV were ventilated with tidal volume of 8ml/kg and zero PEEP. We collected bronchial lavage fluid of all patients before surgery and at the end of operation to detect TNF-α,IL-1β,IL-6 and IL-8 level in BALF. And Oxygenation Index, postoperative CT scan of lungs as well as incidence rate of complications were collected.
Results
The results showed that IL-1 and IL-8 levels in BALF of Group PV were significantly lower than that of Group CV. Oxygenation Index of was significantly higher in patients of Group PV. Cases with postoperative complications in Group PV was less than that in Group CV, but that difference was not significant.
Conclusion
The trial suggested that protective ventilation strategy could attenuate release of cytokines and improve postoperative oxygenation capacity. Maybe the sample size of this trial was relatively small to detect the difference of incident rate of ARDS/ALI and other complications between two groups, so we would carry out a further tiral with a large sample capacity to fix the problem.
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