持续低剂量肝素和低分子肝素抗凝治疗对急性呼吸窘迫综合征患者预后的荟萃分析  

Meta-analysis of the impact of continuous anticoagulation therapy with low-dose heparin or low molecular weight heparin on the prognosis of patients with acute respiratory distress syndrome

作　　者：郑兴昊 沈锋 李想 杨贵霞 程玉梅 何天慧 李书文 秦进成 李清 李伟 Zheng Xinghao;Shen Feng;Li Xiang;Yang Guixia;Cheng Yumei;He Tianhui;Li Shuwen;Qin Jincheng;Li Qing;Li Wei(Department of Critical Care Medicine,Guizhou Medical University Affiliated Hospital,Guiyang 550004,Guizhou,China)

机构地区：[1]贵州医科大学附属医院重症医学科,贵阳550004

出　　处：《中华危重病急救医学》2020年第12期1479-1486,共8页Chinese Critical Care Medicine

基　　金：贵州省科技计划项目(黔科合基础[2019]1261)。

摘　　要：目的通过系统分析方法评价持续低剂量肝素及低分子肝素抗凝治疗对急性呼吸窘迫综合征(ARDS)患者的疗效及安全性。方法检索万方数据库、维普数据库、中国知网(CNKI)、中国生物医学文献服务系统(SinoMed)、美国国立医学图书馆数据库(PubMed)、荷兰医学文摘数据库(Embase)、Cochrane图书馆数据库等中英文数据库中1999年7月至2020年6月发表的有关肝素或低分子肝素治疗ARDS的临床随机对照试验(RCT)。对照组给予常规治疗,试验组在常规治疗基础上加用肝素5~10 U·kg^(-1)·h^(-1)或低分子肝素皮下注射2500~5000 U,每12 h 1次,疗程均为7 d;主要结局指标为28 d病死率、治疗7 d后动脉血氧饱和度(SaO2)及急性生理学与慢性健康状况评分Ⅱ(APACHEⅡ)、重症监护病房(ICU)住院时间及机械通气时间;次要结局指标为治疗7 d后C-反应蛋白(CRP)、肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)、肺损伤评分、呼吸频率、活化部分凝血活酶时间(APTT)、凝血酶原时间(PT)等指标。由2名研究者收集数据,依据Cochrane 5.1手册评价文献质量,采用RevMan 5.3软件进行Meta分析;Meta分析结果的稳定性用敏感性分析方法检验,同时通过漏斗图分析SaO2的发表偏倚。结果最终纳入14篇中文文献,共涉及894例患者,其中试验组454例,对照组440例。Meta分析结果显示,与对照组相比,试验组28 d病死率明显降低〔相对危险度(RR)=0.54,95%可信区间(95%CI)为0.38~0.76,P=0.0004〕,治疗7 d SaO2均显著升高〔肝素:均数差(MD)=48.27,95%CI为29.95~66.59,P<0.00001;低分子肝素:MD=56.67,95%CI为41.22~71.13,P<0.00001〕;与对照组相比,治疗7 d后试验组APACHEⅡ评分(MD=-4.28,95%CI为-5.15^-3.42,P<0.00001)、肺损伤评分(MD=-1.19,95%CI为-1.35^-1.03,P<0.00001)及呼吸频率(MD=-4.76,95%CI为-6.26^-3.26,P<0.00001)均明显降低,试验组患者ICU住院时间(MD=-4.85,95%CI为-6.94^-2.76,P<0.00001)、机械通气时间(MD=-2.93,95%CI为-3.34s database(Embase)and Cochrane library database were searched for the randomized controlled trials(RCTs)of heparin or low molecular weight heparin in the treatment of ARDS.The search time is from July 1999 to June 2020.The control group was given routine treatment,while the experimental group was given heparin 5-10 U·kg^(-1)·h^(-1),or low molecular heparin subcutaneous injected 2500-5000 U once every 12 hours for 7 days on the basis of the routine treatment.The main outcome were 28-day mortality,arterial oxygen saturation(SaO2),acute physiology and chronic health evaluationⅡ(APACHEⅡ),length of stay in intensive care unit(ICU)and mechanical ventilation time,and the secondary outcome indexes were C-reactive protein(CRP),tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),lung injury score,respiratory frequency,activated partial thromboplastin time(APTT)and prothrombin time(PT)after 7 days'treatment.The two researchers collected data and evaluated the quality of the literature according to the Cochrane 5.1.The stability of the Meta-analysis results was tested by sensitivity analysis,and the publication bias was included in the funnel chart analysis.Results Fourteen Chinese literatures were included,with a total of 894 cases,including 454 cases in the experimental group and 440 cases in the control group.The results of Meta-analysis showed that the 28-day fatality rate in the experimental group was significantly lower than that in the control group[relative risk(RR)=0.54,95%confidence interval(95%CI)was 0.38-0.76,P=0.0004],and 7-day SaO2 significantly increased[heparin:mean difference(MD)=48.27,95%CI was 29.95-66.59,P<0.00001].Low molecular weight heparin:MD=56.67,95%CI was 41.22-71.13,P<0.00001].Compared with the control group,the APACHEⅡscore(MD=-4.28,95%CI was-5.15 to-3.42,P<0.00001),the lung injury score(MD=-1.19,95%CI was-1.35 to-1.03,P<0.00001)and the respiratory rate(MD=-4.76,95%CI was-6.26 to-3.26,P<0.00001)in the experimental group were significantly lower than those in the control group after 7 day

关 键 词：急性肺损伤 急性呼吸窘迫综合征 抗凝治疗 肝素 低分子肝素 预后 

分 类 号：R563.8[医药卫生—呼吸系统]