Yao Yun-Tai, Fang Neng-Xin, Liu Ding-Hua, Li Li-Huan
Department of Anesthesiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing.
Department of Clinical Laboratory, University-Town Hospital of Chongqing Medical University, Chongqing, China.
Medicine (Baltimore). 2020 Feb;99(7):e19184. doi: 10.1097/MD.0000000000019184.
Ulinastatin is a type of glycoprotein and a nonspecific wide-spectrum protease inhibitor like antifibrinolytic agent aprotinin. Whether Ulinastatin has similar beneficial effects on blood conservation in cardiac surgical patients as aprotinin remains undetermined. Therefore, a systematic review and meta-analysis were performed to evaluate the effects of Ulinastatin on perioperative bleeding and transfusion in patients who underwent cardiac surgery.
Electronic databases were searched to identify all clinical trials comparing Ulinastatin with placebo/blank on postoperative bleeding and transfusion in patients undergoing cardiac surgery. Primary outcomes included perioperative blood loss, blood transfusion, postoperative re-exploration for bleeding. Secondary outcomes include perioperative hemoglobin level, platelet counts and functions, coagulation tests, inflammatory cytokines level, and so on. For continuous variables, treatment effects were calculated as weighted mean difference (WMD) and 95% confidential interval (CI). For dichotomous data, treatment effects were calculated as odds ratio and 95% CI. Statistical significance was defined as P < .05.
Our search yielded 21 studies including 1310 patients, and 617 patients were allocated into Ulinastatin group and 693 into Control (placebo/blank) group. There was no significant difference in intraoperative bleeding volume, postoperative re-exploration for bleeding incidence, intraoperative red blood cell transfusion units, postoperative fresh frozen plasma transfusion volumes and platelet concentrates transfusion units between the 2 groups (all P > .05). Ulinastatin reduces postoperative bleeding (WMD = -0.73, 95% CI: -1.17 to -0.28, P = .001) and red blood cell (RBC) transfusion (WMD = -0.70, 95% CI: -1.26 to -0.14, P = .01), inhibits hyperfibrinolysis as manifested by lower level of postoperative D-dimer (WMD = -0.87, 95% CI: -1.34 to -0.39, P = .0003).
This meta-analysis has found some evidence showing that Ulinastatin reduces postoperative bleeding and RBC transfusion in patients undergoing cardiac surgery. However, these findings should be interpreted rigorously. Further well-conducted trials are required to assess the blood-saving effects and mechanisms of Ulinastatin.
乌司他丁是一种糖蛋白，是一种非特异性广谱蛋白酶抑制剂，类似于抗纤溶药物抑肽酶。乌司他丁对心脏手术患者血液保护是否具有与抑肽酶类似的有益作用仍未确定。因此，进行了一项系统评价和荟萃分析，以评估乌司他丁对心脏手术患者围手术期出血和输血的影响。
检索电子数据库，以确定所有比较乌司他丁与安慰剂/空白对照对心脏手术患者术后出血和输血影响的临床试验。主要结局包括围手术期失血量、输血、术后因出血再次手术探查。次要结局包括围手术期血红蛋白水平、血小板计数及功能、凝血试验、炎症细胞因子水平等。对于连续变量，治疗效果计算为加权均数差（WMD）和95%置信区间（CI）。对于二分数据，治疗效果计算为比值比和95%CI。统计学显著性定义为P<0.05。
我们的检索共纳入21项研究，包括1310例患者，其中617例患者被分配到乌司他丁组，693例患者被分配到对照组（安慰剂/空白对照）。两组之间术中出血量、术后因出血再次手术探查发生率、术中红细胞输注单位、术后新鲜冰冻血浆输注量和血小板浓缩物输注单位均无显著差异（均P>0.05）。乌司他丁可减少术后出血（WMD=-0.73，95%CI：-1.17至-0.28，P=0.001）和红细胞（RBC）输注（WMD=-0.70，95%CI：-1.26至-0.14，P=0.01），通过降低术后D-二聚体水平抑制高纤溶状态（WMD=-0.87，95%CI：-1.34至-0.39，P=0.0003）。
这项荟萃分析发现一些证据表明，乌司他丁可减少心脏手术患者的术后出血和RBC输注。然而，这些发现应谨慎解读。需要进一步开展高质量的试验来评估乌司他丁的血液保护作用及机制。
