血必净联合乌司他丁对重症脓毒症的疗效及作用机制的研究

Study on curative effect and mechanism of Xuebijing combined with ulinastatin in severe sepsis patients

目的评价血必净联合乌司他丁对重症脓毒症患者的疗效和安全性,并通过观察患者细胞因子的变化来探讨其可能的作用机制。方法将228例重症脓毒症患者随机分为乌司他丁组、血必净组、血必净+乌司他丁组、对照组。对照组按照严重脓毒症治疗指南进行治疗。在对照组治疗基础上,乌司他丁组加用乌司他丁20万U iv q12h,7d为一疗程;血必净组加用血必净注射液100mL ivgtt q12h,7d为一疗程;血必净+乌司他丁组加用血必净注射液100mL ivgtt q12h+乌司他丁20万Uivq12h,7d为一疗程。在治疗前及治疗第4、8天分别抽取静脉血测定血浆内毒素(LPS)、肿瘤坏死因子α(TNF-α)、白细胞介素-6(IL-6)、前降钙素(PCT),并统计机械通气时间、ICU住院时间、28d生存率。结果四组患者治疗后LPS、IL-6、TNF-α、PCT水平均下降,其中血必净+乌司他丁治疗组在第4、8天下降幅度显著大于单一血必净治疗组、单一乌司他丁治疗组和对照组(两两比较P均<0.01)。血必净+乌司他丁治疗组机械通气时间、ICU住院时间明显少于单一血必净治疗组、单一乌司他丁治疗组和对照组,而28d生存率呈现相反趋势(两两比较P均<0.05)。结论血必净联合乌司他丁能够显著改善重症脓毒症患者的病情,缩短机械通气时间和ICU住院时间,提高生存率;作用机制可能是拮抗LPS,阻断Toll样受体,抑制促炎因子释放,降低血清PCT水平。

Objective To evaluate the curative effect and safety of Xuebijing combined with ulinastatin in the patients with severe sepsis and to investigate it＇s mechanisms. Methods 228 severe sepsis patients were randomly divided into ulinastatin treatment group（group A ）, Xuebijing treatment group （group B）, Xuebijing combined with ulinastatin treatment group（group C） and control group（group D）. The patients in the control group were treated according to the therapy guideline of severe sepsis. Besides the treatment in the control group, patients in group A received ulinastatin 200 000 Units intravenously twice a day for 7 days ; the patients in group B received Xuebijing injection 100 mL intravenous drip twice a day for 7 days ; the patients in group C received both Xuebijing injection and ulinastatin used in group B and group A. Before the treatment and on 4 th,8 th day after the treatment, blood concentrations of LPS, TNF- α, IL -6, PCT were determined, and the time of mechanical ventilation, the days in ICU, the 28 -day survival rate were compared among the four groups. Results LPS, IL- 6, TNF-α, PCT in all the groups decreased after the treatment, and the descending degree in group C on 4th and 8th day was more obvious than that in group A, group B and group D. There were significant differences among the four groups （ all P 〈 0.01 ）. The time of mechanical ventilation and the days in ICU were shorter in group C than those in group A, group B and group D, but the 28 - day survival rate showed opposite tendency. There were significant differences among the four groups I all P 〈 0.05 ）. Conclusions The treatment of Xuebi-jing combined with ulinastatin significantly improves patient＇s condition, reduces the time of mechanical ventilation, the days in ICU, and improves survival rate. The mechanisms are antagonizing endotoxin, intercepting Toll - like receptors, inhibiting proinflammatory eytokines and lowering the level of serum PCT.