目的:比较不同剂量蛋白酶抑制剂乌司他丁对高危肝移植手术患者术后的器官保护作用。方法回顾性队列分析2003年1月至2014年7月在中山大学附属第三医院器官移植中心146例术中失血量3000 ml以上的肝移植患者的临床资料。所有患者均签署知情同意书,治疗符合医学伦理学规定。根据术后静脉使用乌司他丁剂量将上述高危患者分为大剂量组(HD组:400 kU,q6 h)和常规剂量组(RD组:400 kU,q12 h)。HD组63例,术中失血量(5.0±2.9)L,术后当天APACHEⅡ评分20.9±7.5、SOFA评分15.0±3.2;RD组83例,术中失血量(6.2±4.5)L,术后当天APACHEⅡ评分20.0±7.4、SOFA评分14.6±3.4。观察静脉应用乌司他丁5 d治疗后第3、7天APACHEⅡ评分和SOFA评分改变。同时了解两组患者感染发生率、机械通气时间、ICU停留时间、肾替代治疗比例以及90 d生存曲线。连续性资料如符合正态分布采用t检验,非正态分布采用非参数检验;分类资料率的比较采用χ2检验。结果两组患者年龄、性别、术前MELD评分、CTP评分、术中失血量、输血量、手术时间、无肝期时间、术后当天APACHEⅡ和SOFA评分无统计学差异。静脉应用5 d乌司他丁后,未观察到有不良反应发生。虽然两组术后90 d生存曲线无统计学差异(χ2=0.566, P=0.452),但HD组第3天和第7天的APACHEⅡ评分、第7天的SOFA评分改善更为明显(5.6±4.5 vs.3.6±3.4,t=-2.910,P=0.004;8.5±4.7 vs.4.5±3.9,t=-5.468,P<0.001;4.7±3.2 vs.3.2±2.8, t=-2.944,P=0.004);RD/HD感染发生率(39.6%vs.23.8%,OR 2.11,95%CI 1.02~4.37,χ2=4.129,P=0.042)、肾替代治疗比例(22.9%vs.9.5%,OR 2.82,95%CI 1.05~7.55,χ2=4.51,P=0.034)、机械通气时间(Z=-5.112,P<0.01)、ICU停留时间(Z=-2.604,P<0.01)较RD组均有统计学差异。结论大剂量乌司他丁能显著改善高危肝移植术后患者?
Objective To explore whether early use of the increased dose of intravenous ulinastatin improves outcomes in the liver transplant recipients. Methods The cohort study was conducted to investigate clinical data of 146 liver transplant recipients who suffered at least 3 000 ml blood lost during operation performed in the transplantation center of 3rd affiliated hospital, Sun Yat-Sen University. All cases were complied with requirements of medical ethic rules and signed informed consent. A total of 83 patients were treated with intravenous Ulinastatin on a daily dose 400 kU, iv drip, q6 h were assigned to the High-dose group (HD) or the exposure group; the other 63 patients were assigned to the Routine dose group (RD) or the control group with a daily dose of 400 kU, iv drip, q12 h. Any case should be treated with Ulinastatin at least 5 days. Raw data were collected to calculate the APACHEⅡand SOFA score 3 days and 7 days after transplantation. APACHEⅡ,SOFA score and the score changes (ΔA,ΔS), morbidity of sepsis and renal replacement therapy, duration of ventilation and ICU-stay, mortality and the survive curve differences were measured. Results There were no differences between the two groups of the base line characteristics likes the demographic data, MELD and CTP score, operative blood lost and transfusion, anhepatic time, operation duration and the immediate APACHEⅡ, SOFA score (P>0.05). None of any relevant side-effect occurred during therapies. On the 3rd and 7th post-transplant day, the APACHEⅡ decreased more sharply in HD group versus RD group (t=-2.910, P=0.004; t=-5.468, P<0.001); SOFA decreased more in HD group on the 7th post-transplant day (t=-2.944, P=0.004). Morbidity like sepsis and renal failure with necessary renal replacement therapy were significantly lower in the HD group (39.6% vs. 23.8%, OR 2.11, 95% CI 1.02-4.37,χ2=4.129, P=0.042; 22.9% vs. 9.5%, OR 2.82, 95%CI 1.05-7.55,χ2=4.51, P=0.034);Duration of ventilation and ICU stay were much less in