乌司他丁胸腺肽α-1联合或单独治疗严重脓毒症的Meta分析

Ulinastatin and thymosin al combined therapy or monotherapy for severe sepsis： a meta - analysis

目的：综合分析乌司他丁（ulinastatin， UTI）、胸腺肽α1（thymosin α1， Tα1）联合或单独治疗严重脓毒症的安全性和有效性。方法检索PubMed、Embase和Cochrane Library数据库中收录的有关UTI、Tα1联合或单独治疗严重脓毒症的相关文献，依据Cochrane 系统评价手册5.1．0版推荐的质量评价标准对随机对照试验（ randomized controlled trial ， RCT ）进行评价，使用Review Manager 5．3统计学软件进行数据分析和综合，并绘制森林图和漏斗图。结果共纳入10篇文献，12项研究。试验组和对照组比较的亚组分析结果显示：①UTI联合Tα1亚组中，28 d死亡率差异有统计学意义[RR＝0．67，95％CI（0．57，0．80）， P＜0．00001]，90 d死亡率差异有统计学意义[ RR＝0．74，95％ CI （0．64，0．85）， P＜0．0001]，机械性通气时间差异有统计学意义[MD＝－1．51，95％ CI（－2．93，－0．09）， P＝0．04]，28 d APACHEⅡ评分差异有统计学意义[MD＝－3．39，95％CI（－5．89，－0．90）， P＝0．008]。②UTI亚组中，机械性通气时间差异有统计学意义[MD＝－4．40，95％CI（－7．55，－1．25）， P＝0．006]。③ Tα1亚组中，28 d死亡率差异有统计学意义[RR＝0．72，95％CI （0．55，0．93）， P＝0．01]，抗生素使用时间差异有统计学意义[MD＝－6．00，95％ CI（－8．14，－3．86）， P＜0．00001]。结论依据目前的资料，UTI联合Tα1能够降低严重脓毒症患者28 d死亡率、90 d死亡率、机械性通气时间和28 d APACHEⅡ评分，UTI能够降低机械性通气时间，Tα1能够降低28 d死亡率和抗生素使用时间，但各亚组纳入研究较少，次要结局指标间异质性较大，进一步的结论有待更多高质量的RCT进行验证。

Objective To analyze the safety and effectiveness of ulinastatin （UTI） and thymosin cd （Tαl） combined therapy or monotherapy for severe sepsis. Methods PubMed, Embase and Cochrane Library were searched for the literature which was about UTI and/or Tcd for severe sepsis. Randomized controlled trial （RCT） was evaluated by the Cochrane handbook 5. 1.0. Analyses and syntheses of data were performed and forest plot and funnel plot were drawn by the Review Manager 5.3 statistics software. Results 10 articles and 12 studies were taken into meta -analysis. The statistical analysis results between experimental group and control group in subgroups were as follows： （~）In the subgroup of UTI and Tcxl, there were significant differences in 28 - day mortality [ RR = 0.67, 95% CI （0.57, 0.80）, P 〈 O. 00001 ] ; there were significant differences in 90 - day mortality [ RR = 0.74, 95% CI （0.64, 0.85 ）, P 〈 0. 0001 ] ; there were significant differences in length of mechanical ventilation [ MD = - 1.51,95% CI （ -2.93, -0.09）, P =0.04] ; there were significant differences in 28 - day APACHE Ⅱ scores [MD= -3.39, 95% CI （ -5.89, -0.90）, P=0.008]. Inthesubgroup of UTI, there were significant differences in length of mechanical ventilation [ MD = - 4.40, 95% CI （ -7.55, - 1.25）, P =0.006]. （~）In the subgroup of Ted, there were significant differences in28 - day mortality [RR =0. 72, 95% CI （0.55, O. 93）, P =0. 01]; there were significant differences in length of antibiotics use [ MD = -6.00, 95% CI （ - 8.14, - 3.86）, P 〈 0. 00001 ]. Conclusion According to the current data, UTI and Tctl combined therapy for severe sepsis can reduce 28 - day mortality, 90 - day mortality, length of mechanical ventilation and 28 - day APACHE lI scores. UTI can reduce length of mechanical ventilation. Ted can reduce 28 - day mortality and length of antibiotics use. However, there are a small number of studies in each subgroup and the heterogeneity in secondary outcomes is obvious, and the further conclusion needs to be validated by more high quality RCTs.