国际麻醉学与复苏杂志   2020, Issue (9): 5-5
    
乌司他丁对肝移植患者呼出气冷凝液中炎症因子和肺功能的影响
蔡俊刚, 魏昌伟, 罗婷, 吴安石1()
1.北京大学国际医院
Effects of ulinastatin on inflammatory factors and lung function in exhaled condensate of liver transplant patients
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摘要:

目的 分析乌司他丁对肝移植患者呼出气冷凝液中炎症因子和肺功能的影响。 方法 选取2016年4月至2017年4月在北京朝阳医院进行原位肝移植(orthotopic liver transplantation, OLT)手术的患者50例,按照随机数字表法分为两组(每组25例):乌司他丁组(U组)与生理盐水对照组(N组)。U组将乌司他丁10 kU/kg用生理盐水稀释至100 ml,在切皮前开始进行持续静脉输注,N组用等容量生理盐水代替。分别于用药前10 min(T1)、阻断肝血流前10 min(T2)、阻断肝血流后30 min(T3)、开放肝血流后30 min(T4)及手术结束前10 min(T5)抽取桡动脉血行血气分析,同时抽取肺动脉血;分别于用药前20 min(ET1)、阻断肝血流前20 min(ET2)、阻断肝血流后20 min(ET3)、开放肝血流后20 min(ET4)、手术结束前20 min(ET5)收集呼出气冷凝液(exhaled breath condensate, EBC),收集时长20 min。检测两组患者上述时点EBC与肺动脉血血清中TNF‑α、IL‑8、IL‑10及中性粒细胞弹性蛋白酶(neutrophil elastase, NE)水平,并记录T1~T5时点的气道峰压(peak airway pressure, Ppeak)、肺动态顺应性(pulmonary dynamic compliance, Cdyn)、PaO2、肺泡气‑动脉血氧分压差[alveolar‑arterial oxygen difference, P(A‑a)O2]、氧合指数(oxygenation index, OI)、呼吸指数(respiratory index, RI)等呼吸力学和肺功能指标,以及术后3 d内肺部并发症情况。 结果 两组患者各时点Ppeak、Cdyn差异无统计学意义(P>0.05)。T4时U组RI低于N组,OI高于N组(P<0.05);与T1时比较,N组在T4、T5时OI降低(P<0.05)。两组患者各时点EBC和血清中NE水平比较无统计学差异(P>0.05)。与ET1时比较,两组患者ET4、ET5时EBC中TNF‑α水平降低(P<0.05);U组ET5时EBC中TNF‑α水平低于N组(P<0.05)。与T1时比较,U组T4、T5时血清中TNF‑α水平降低(P<0.05);U组T4、T5时血清中TNF‑α水平低于N组(P<0.05)。与ET1时比较,N组ET5时,U组ET3、ET4、ET5时EBC中IL‑8水平降低(P<0.05);U组ET4、ET5时EBC中IL‑8水平低于N组(P<0.05)。与T1时比较,N组T4、T5时,U组T3、T4、T5时血清中IL‑8水平降低(P<0.05);U组T4、T5时血清中IL‑8水平低于N组(P<0.05)。与ET1时比较,N组ET3、ET4、ET5时EBC中IL‑10水平降低,U组ET4、ET5时EBC中IL‑10水平升高(P<0.05);U组ET4、ET5时EBC中IL‑10水平高于N组(P<0.05)。与T1时比较,N组T3、T4、T5时血清中IL‑10水平降低,U组T4、T5时血清中IL‑10水平升高(P<0.05);U组T4、T5时血清中IL‑10高于N组(P<0.05)。术后3 d内,U组患者肺部并发症发生率(40%)低于N组(72%)(P<0.05)。 结论 EBC中炎性细胞因子水平能够反映患者肺损伤情况,应用乌司他丁能够减轻EBC中炎症因子水平,从而降低术后肺部并发症。

关键词: 肝移植; 乌司他丁; 呼出气冷凝液; 炎症因子; 肺功能
Abstract:

Objective To analyze the effect of ulinastatin on inflammatory factors and lung function in exhaled breath condensate (EBC) of liver transplantation patients. Methods From April 2016 to April 2017, 50 cases of orthotopic liver transplantation (OLT) patients in Beijing Chaoyang Hospital were divided into two groups (25 cases in each group) using random number table method: ulinastatin group (group U) and saline control group (group N). Ulinastatin 10 kU/kg was diluted into 100 ml normal saline and continuous intravenous infusion was started before skin incision in group U, while equal volume normal saline was used in group N. The blood samples of radial artery and pulmonary artery were collected for blood gas analysis at 10 min before medication (T1), 10 min before hepatic blood flow occlusion (T2), 30 min after blocking hepatic blood flow (T3), 30 min after opening hepatic blood flow (T4) and 10 min before the end of operation (T5). EBC was collected at 20 min before treatment (ET1), 20 min before blocking hepatic blood flow (ET2), 20 min after blocking hepatic blood flow (ET3), 20 min after opening hepatic blood flow (ET4) and 20 min before the end of operation (ET5), the length of EBC collection was 20 min. The levels of tumor necrosis factor‑α (TNF‑α), interleukin (IL)‑8, IL‑10 and neutrophil elastase (NE) in EBC and serum at the above time points were detected, and the peak airway pressure (Ppeak), pulmonary dynamic compliance (Cdyn), arterial partial pressure (PaO2), alveolar‑arterial oxygen difference [P(A‑a)O2], oxygenation index (OI), respiratory index (RI) and other respiratory mechanics and pulmonary function indexes at T1‒T5 were recorded. Pulmonary complications within 3 days after operation were also recorded. Results There was no significant difference in Ppeak and Cdyn between the two groups (P>0.05). RI in group U was lower than that in group N at T4 (P<0.05), OI in group U was higher than that in group N at T4 (P<0.05). OI in group N was lower at T4 and T5 compared with T1 (P<0.05). Level of NE: There was no statistical significance in EBC and serum at each time point (P>0.05). Level of TNF‑α: Compared with ET1, the levels of TNF‑α at ET4 and ET5 in both groups were lower (P<0.05), the level of TNF‑α at ET5 in group U was lower than that in group N (P<0.05), compared with T1, the level of TNF‑α at T4 and T5 in group U was lower (P<0.05), the level of TNF‑α at T4 and T5 in group U was lower than that in group N (P<0.05). IL‑8 level: Compared with ET1, the levels of IL‑8 in EBC decreased at ET5 in group N and at ET3, ET4 and ET5 in group U (P<0.05), the levels of IL‑8 in EBC was lower in group U than that in group N at ET4 and ET5 (P<0.05), compared with T1, serum levels of IL‑8 in group N at T4 and T5 and in group U at T3, T4 and T5 were reduced (P<0.05), the serum levels of IL‑8 in group U at T4 and T5 was lower than that in group N (P<0.05). IL‑10 level: Compared with ET1, the levels of IL‑10 at ET3, ET4 and ET5 in group N were lower (P<0.05), the levels of IL‑10 at ET4 and ET5 in group U were higher (P<0.05), the levels of IL‑10 at ET4 and ET5 in group U were higher than those in group N (P<0.05). Compared with T1, the levels of IL‑10 at T3, T4 and T5 in group N were lower, the levels of IL‑10 at T4 and T5 in group U were higher (P<0.05). The levels of IL‑10 at T4 and T5 in group U were higher than those in group N (P<0.05). Within 3 days after operation, the incidence of pulmonary complications in group U (40%) was lower than that in group N (72%) (P<0.05). Conclusions The level of inflammatory cytokines in EBC can reflect the lung injury of patients. Ulinastatin can reduce the level of inflammatory factors in EBC, thus reducing the postoperative pulmonary complications.

Key words: Liver transplantation; Ulinastatin; Exhaled breath condensate; Inflammatory factor; Lung function