Li Mei-Juan, Shi Jin-Ying, Zhang Jin-Hua
Department of Pharmacy, First Hospital of Shanxi Medical University, Taiyuan, Shanxi, China.
Department of Neurology, and Fujian Key Laboratory of Molecular Neurology, Fujian Medical University Union Hospital, Fuzhou, Fujian, China.
Br J Clin Pharmacol. 2022 Jun;88(6):2605-2616. doi: 10.1111/bcp.15251. Epub 2022 Feb 14.
Unfractionated heparin (UFH) has been the primary anticoagulant of choice on extracorporeal membrane oxygenation (ECMO). However, it is debatable whether bivalirudin (BIV), a direct thrombin inhibitor, may be considered a better alternative anticoagulant option.
We searched Embase, Pubmed, Cochrane library, Clinicaltrials.gov, CNKI and Wanfang databases up to 15 June 2021. Randomized controlled trials and observational studies were considered eligible for inclusion. Random-effects meta-analyses, including subgroup analyses, were conducted.
A total of 9 studies containing 994 patients were enrolled. All articles were retrospective cohort studies. Compared with UFH, BIV was associated with lower risks of major bleeding (risk ratio [RR]: 0.32, 95% confidence interval [CI] 0.22-0.49), ECMO in-circuit thrombosis (RR: 0.57, 95% CI 0.43-0.74), stroke (RR: 0.52, 95% CI 0.29-0.95) and in-hospital mortality (RR: 0.82, 95% CI 0.69-0.99), and higher rates of survival to ECMO decannulation (RR: 1.18, 95% CI 1.03-1.34). Pooled risk estimates did not show a significant association with clinical thrombotic events (RR: 0.69, 95% CI 0.45-1.07). Moreover, BIV was associated with a lower risk of ECMO in-circuit thrombosis and in-hospital mortality in the adult subgroup but not in the paediatric subgroup. However, leave-one-out sensitivity analyses indicated that the results of stroke, survival to ECMO decannulation and in-hospital mortality should be interpreted with caution.
BIV appears to be a potential alternative to UFH in paediatric and adult patients requiring ECMO.
普通肝素(UFH)一直是体外膜肺氧合(ECMO)中首选的抗凝剂。然而,直接凝血酶抑制剂比伐卢定(BIV)是否可被视为更好的替代抗凝剂选择仍存在争议。
我们检索了截至2021年6月15日的Embase、Pubmed、Cochrane图书馆、Clinicaltrials.gov、中国知网和万方数据库。随机对照试验和观察性研究被认为符合纳入标准。进行了随机效应荟萃分析,包括亚组分析。
共纳入9项研究,包含994例患者。所有文章均为回顾性队列研究。与UFH相比,BIV与大出血风险较低(风险比[RR]:0.32,95%置信区间[CI]0.22 - 0.49)、ECMO回路内血栓形成风险较低(RR:0.57,95%CI 0.43 - 0.74)、中风风险较低(RR:0.52,95%CI 0.29 - 0.95)以及住院死亡率较低(RR:0.82,95%CI 0.69 - 0.99)相关,并且ECMO撤机生存率较高(RR:1.18,95%CI 1.03 - 1.34)。汇总风险估计显示与临床血栓形成事件无显著关联(RR:0.69,95%CI 0.45 - 1.07)。此外,BIV与成人亚组中ECMO回路内血栓形成和住院死亡率较低相关,但与儿科亚组无关。然而,逐一剔除敏感性分析表明,中风、ECMO撤机生存率和住院死亡率的结果应谨慎解释。
在需要ECMO的儿科和成人患者中,BIV似乎是UFH的一种潜在替代药物。