不同剂量乌司他丁对体外循环心脏术后肾损伤的影响

Effect of different dose of ulinastatin on kidney injury in patients undergoing cardio-pulmonary bypass

目的:观察不同剂量乌司他丁(UTI)对体外循环(CPB)心脏术后患者肾损伤的影响,探讨大剂量乌司他丁是否能明显减轻体外循环心脏手术对肾脏的损伤,并考察其临床安全性。方法:择60例择期进行心脏手术的患者,随机分为治疗组(U_1、U_2、U_3组)及对照组(C组),每组15人,治疗组分别于预充液中一次性给予乌司他丁2万U·kg^(-1)、4万U·kg^(-1)及6万U_·kg-1,对照组按照临床常规用量(术中预充液中加入10万U,术后10万U q8h静脉滴注用至术后48 h),各组均分别于术前30 min(T_0)、术后第1天(T_1)、第3天(T_3)、第5天(T_5)及第7天(T_7)共5个时间点抽取静脉血,测定血清中肌酐(Cr)及尿素氮(BUN)水平,同时记录入组患者的基本信息并密切观察用药期间临床不良事件发生情况。结果:(1)肌酐(Cr):4组术后T_1、T_3点肌酐水平高于T_0值(P<0.05),3组治疗组术后各时间点肌酐水平低于C组(P<0.05),U_2、U_3组术后各时间点肌酐水平低于U_1组且差异具有显著性(P<0.05),U_1组与对照组相比差异均无显著性(P>0.05),U_3组与U_2组相比两指标差异均无显著性(P>0.05)。(2)尿素氮(BUN):U_1组尿素氮水平低于对照组且差异具有显著性(P<0.05),其余变化同肌酐。(3)安全性:研究期间各剂量组均无乌司他丁相关不良反应发生。结论:体外循环心脏手术能够造成患者肾功能损伤,而乌司他丁能减轻围术期肾损伤,且在一定范围内呈剂量相关性,各剂量组安全性良好。适宜应用剂量为4万U·kg^(-1),预充液中一次性加入。

OBJECTIVE To observe the kidney injury in patients undergoing cardio-pulmonary bypass,and investigate the effect and safety of different dose of ulinastatin in protecting renal functions.METHODS Sixty patients undergoing cardio-pulmonary bypass were randomly divided into four groups：three experimental groups（group U1,n=15;group U2,n=15;group U3,n=15）and control group（group C,n=15）.In three experimental groups,20 000 U·kg^-1,40 000 U·kg^-1 and60 000 U·kg^-1 ulinastatin was added to the priming solution,respectively;in group C,100 000 U of ulinastatin was added to the priming solution and 100 000 U q8 h was infused i.v.in the first two days postoperatively.Blood samples were harvested in the day before operation（T0）,the first day（T1）,the third day（T3）,the fifth day（T5）,and the seventh day（T7）after operation,for measurement of serum creatinine（Cr）and urea nitrogen（BUN）.The related information of enrolled patients was recorded,and clinical drug adverse events were observed closely.RESULTS Cr levels at T1 and T3 were higher than that at T0（P〈0.05）,the postoperative levels in experimental groups were lower than that in the control group（P〈0.05）,and the postoperative levels in group U2 and group U3 were lower than that in group U1（P〈0.05）,but the difference between group U2 and group U3 was not significant（P〉0.05）.BUN level in group U1 was lower than that in control group（P〈0.05）,the other trend of BUN was approximately the same with Cr.Ulinastatin showed no adverse event during the study period.CONCLUSION Cardio-pulmonary bypass will cause kidney injury,and different doses of ulinastatin can protect the renal function more or less with good safety in a dose dependent manner.Based on the result,it is suggested to add 40 000 U·kg^-1 of ulinastatin to the priming solution in patients undergoing cardio-pulmonary bypass.