比伐卢定与肝素用于儿童及青少年体外膜肺氧合抗凝的有效性与安全性比较的Meta分析

Meta-Analysis on Efficacy and Safety of Bivalirudin and Heparin for Anticoagulation in Extracorporeal Membrane Oxygenation in Children and Adolescents

目的:系统评价比伐卢定与肝素用于儿童及青少年体外膜肺氧合(ECMO)抗凝的有效性与安全性。方法:计算机检索PubMed、the Cochrane Library、EMBase、万方、中国知网(CNKI)及维普(VIP)等数据库,搜集有关比伐卢定与肝素用于儿童及青少年ECMO抗凝的临床研究,检索时限均为建库至2022年9月5日,由2名研究者独立筛选文献、提取资料并采用纽卡斯尔-渥太华量表(NOS)对纳入文献进行质量评估,采用Rev Man 5.4软件进行Meta分析。结果:共纳入6篇回顾性队列研究,包括246例患儿。Meta分析结果显示,与肝素比较,比伐卢定显著降低儿童及青少年ECMO抗凝患儿的出血事件(RR=0.30,95%CI 0.15~0.64,P=0.002)及卒中率(RR=0.39,95%CI 0.18~0.84,P=0.02),但病死率(RR=0.95,95%CI 0.70~1.28)、血栓形成发生率(RR=0.94,95%CI 0.34~2.61)、ECMO管路干预发生率(RR=1.08,95%CI 0.53~2.19)、生存率(RR=1.16,95%CI 0.90~1.49)比较差异均无统计学意义。结论:比伐卢定可以显著降低儿童及青少年ECMO抗凝患儿的出血事件和卒中率,在改善病死率、血栓形成发生率、ECMO管路干预发生率、生存率方面优势不明显。由于纳入的研究均为回顾性队列研究,因此本Meta分析的证据水平较低,不可避免存在异质性,迫切需要更高质量的随机双盲对照研究予以验证。

Objective:To systematically evaluate the efficacy and safety of bivalirudin and heparin for anticoagulation in extracorporeal membrane oxygenation(ECMO)in children and adolescents.Methods:PubMed,the Cochrane Library,EMBase,Wanfang,CNKI and VIP databases were retrieved for collecting clinical studies of bivalirudin and heparin for anticoagulation in ECMO in children and adolescents.The retrieval time was from the establishment of the database to Sept.5th,2022.Two researchers independently screened literature,extracted data,and assessed the quality of included studies through the Newcastle-Ottawa Scale(NOS),and Meta-analysis was performed through Rev Man 5.4 software.Results:Six retrospective cohort studies including 246 patients were enrolled.Metaanalysis results indicated that compared with heparin,bivalirudin significantly reduced bleeding events(RR=0.30,95%CI from 0.15 to 0.64,P=0.002)and stroke rates(RR=0.39,95%CI from 0.18 to 0.84,P=0.02)in children and adolescents undergoing ECMO for anticoagulation,yet there were no statistically significant differences in mortality rate(RR=0.95,95%CI from 0.70 to 1.28),incidence of thrombosis(RR=0.94,95%CI from 0.34 to 2.61),circuit intervention rate of ECMO(RR=1.08,95%CI from 0.53 to 2.19),and survival rate(RR=1.16,95%CI from 0.90 to 1.49).Conclusion:Bivalirudin significantly reduces bleeding events and stroke rates in children and adolescents undergoing ECMO,yet the advantages in improving mortality rate,incidence of thrombosis,circuit intervention rate of ECMO and survival rate are not evident.As the included studies were retrospective cohort studies,the evidence level of the Meta-analysis is relatively low,inevitably leading to heterogeneity.Further high-quality randomized double-blind controlled studies are urgently needed for validation.