不同剂量乌司他丁对严重脓毒症和脓毒性休克患者氧化应激及血乳酸的影响

Effects of different dosages of ulinastatin on oxidative stress and blood lactate in patients with severe sepsis and septic shock

目的探讨不同剂量乌司他丁对严重脓毒症和脓毒性休克患者氧化应激水平及血乳酸的影响及其临床意义。方法选择2014年2月-2016年4月海军总医院急诊科EICU收治的127例严重脓毒症以及脓毒性休克患者，随机分为对照组、常规剂量治疗组和大剂量治疗组。三组患者均按照2012年国际严重脓毒症和脓毒性休克治疗指南推荐意见进行治疗。在此基础上，常规剂量组静脉注射乌司他丁30WU／dx5d；大剂量组静脉注射乌司他丁120WU／dx5d；对照组静脉注射等量的生理盐水，分别在用药前租5d后测定血清总超氧化物岐化酶（T—SOD）活力、总抗氧化力（T—hOC）、丙二醛（MDA）含量和血乳酸，比较各组内干预前后以及各组间差别；同时比较三组患者28d病死率。结果干预前三组患者T—SOD活力、T—AOC、MDA、血乳酸无统计学差异（P〉0．05）；5d后两治疗组T—SOD活力和T—AOC显著高于对照组，MDA含量显著低于对照组（P〈0．05）；大剂量组T—SOD活力和T—AOC显著高于常规剂量组，MDA含量显著低于常规剂量组（P〈0．05）；然而，三组患者用药前后血乳酸及28d病死率无统计学差别（P〉0．05）。结论乌司他丁可能会减轻严重脓毒症和脓毒性休克患者体内氧化应激水平，这一作用可能与剂量相关。本研究并未观察到乌司他丁对血乳酸水平的影响，也未能改善28d病死率。

Objective To explore the effects of different dosages of ulinastatin on oxidative stress and blood lactate in patients with severe sepsis and septic shock. Methods 127 patients in EICU in the department of emergency in the Navy General Hospital with severe sepsis or septic shock were selected and randomly divided into control group, conventional dosage treating group and large dosage treating group. Standard therapeutic measures according to 2012 international guidelines for management of severe sepsis and septic shock were implemented in all groups. Besides, the patients in two treating groups were additionally intervened with ulinastatin in vein, 30WU/dx5d of ulinastatin dosages in conventional dosage treating group and 120WU/dx5d dosages in large dosage treating group, while the same volume of saline injection were given in the control group. The oxidative stress indicators of serum malondialdehyde （MDA） contents, total superoxide dismutase （T-SOD） activities and total anti-oxidation capacity （T-AOC） were tested in three groups before intervention and 5 days after, intervention by ulinastatin or saline. Blood lactates were also tested at the same time. Also mortality after 28 days were observed in three groups. Results There were no significant difference of T-SOD activities, T-AOC, MDA contents and blood lactates in three groups before intervention （P〉 0.05）. But 5 days after ulinastatin or saline injection, T-SOD activities and T-AOC were significantly higher and MDA contents were significantly lower in the two treating groups than those in control group （P 〈 0.05）, and also T-SOD activities and T-AOC were significantly higher and MDA contents were significantly lower in large dosage group than those in conventional dosage group （P 〈 0.05）. However, no difference on blood lactates and 28d mortality were found between three groups before and after intervention （P〉 0.05）. Conclusions Ulinastatin maybe protect against the damage of oxidative stress in patients with severe sepsis and septic shock, and this protective effects may be associated with dosages. This study failed to observe beneficial effects on blood lactates and improvement of 25d mortality by ulinastatin among these patients.