不同剂量乌司他丁联合肺保护性通气对肝移植手术患者的肺保护作用

Effects of different doses of ulinastatin combined with lung-protecting mechanical ventilation on cate lung injury during liver transplantation

目的探讨不同剂量乌司他丁联合肺保护性通气对肝移植手术患者肺损伤血清生物标志物和炎性因子的影响。方法选择2014-12至2018-04医院行原位肝移植术的终末期肝病患者60例(终末期肝病评分-MELD评分<15分),随机分为肺保护性通气组(A组),肺保护性通气+5万U/kg乌司他丁(B组)和肺保护性通气+10万U/kg乌司他丁(C组),每组20例。所有患者分别于手术开始前(T1)、无肝前期3 h(T2)、新肝期2 h(T3)及新肝期4 h(T4),检测桡动脉血气及血中肺损伤血清生物标志物,同时,经纤维支气管镜采集肺泡灌洗液(bronchoalveolar lavage fluid,BALF),检测BALF中炎性因子的水平。记录术后2 h、拔管前和术后2 d的氧合指数(PaO2/FiO2)及术后拔管时间、ICU停留时间和急性肺损伤(acute lung injury,ALI)的发生情况。结果与A组比较,B组、C组克拉拉细胞分泌蛋白16(clara cell secretory protein,CC16)、血清表面活性蛋白(surfactant proteins,SP-D)和高级糖基化终末产物可溶性受体(soluble receptor for advanced glycation end-products,sRAGE)水平在T3时均较低,C组CC16水平在T2时也较低;B组BALF中仅肿瘤坏死因子-α(TNF-α)水平在T2、T4时较低,C组TNF-α水平在T2、T3、T4时,白介素-8(IL-8)水平在T3、T4时均较低;B组患者Pa O2/Fi O2仅在T4时较高,C组Pa O2/Fi O2在T2-术后2 h均较高,且平均拔管时间[(6.9±0.9)h&(6.5±1.3)h]和ICU存留时间[(1.9±0.6)d&(1.8±0.4)d]也较短,差异均有统计学意义(P<0.05)。结论乌司他丁联合肺保护性通气能降低肝移植手术患者肺损伤血清标志物和BALF中炎性因子的水平,改善氧合指数,缩短拔管时间和ICU停留时间,较大剂量乌司他丁(10万U/kg)的保护作用更强。

Objective To explore the effecs of different doses of ulinastatin combined with lung-protecting mechanical ventilation on acute lung injury after orthotopic liver transplantation by observing the changes of plasma markers of lung injury and inflammatory mediators. Methods Sixty patients scheduled for liver transplantation under general anesthesia received different doses of ulinastatin combined with the lung-protecting mechanical ventilation strategy. All the patients were randomly divided into three groups: patients in group A were treated with lung-protecting mechanical ventilation alone,group B in which lung-protecting mechanical ventilation was adopted combined with ulinastatin 50,000 U/kg,and group C which was combined with ulinastatin 100,000 U/kg instead. Blood samples were collected from the radial artery for blood gas results and fluid plasma markers of lung injury while bronchoalveolar lavage fluid( BALF) was collected for inflammatory mediators at the following time points: before operation( T1),3 h in the preanhepatic stage( T2),2 h( T3) and 4 h in the neohepatic stage( T4). Plasma markers of lung injury,which were clara cell secretory protein 16( CC16),surfactant proteins( SP-D) and soluble receptor for advanced glycation end-products( sRAGE),and inflammatory mediators such as TNF-α and IL-8,were monitored. Moreover,the oxygenation index( PaO2/FiO2,OI),time of tracheal extubation,length of ICU stay and incidence of acute lung injury within one week were recorded. Results Compared with patients in group A,levels of CC16,SP-D and sRAGE in group B and group C were all lower at T3,so was CC16 in group C at T2. In group B,levels of TNF-α at T2 and T4 were lower,so were levels of TNF-α in group C from T2 to T4 and IL-8 at T2 and T4( P <0. 05). Moreover,PaO2/FiO2( OI) was relatively high in group B at T4,and from T2 to 2 h after operation in group C,where an earlier tracheal extubation and a shorter ICU stay were observed( P <0. 05). Conclusions Ulinastatin( 100,000 U/kg) combined with the lung-protecting mechanical ventilation strategy may contribute to the protection of lung function in patients for liver transplantation,which can lead to lower levels of plasma markers of lung injury and inflammatory mediators,a higher OI,earlier tracheal extubation and a shorter stay of ICU.