连续性肾脏替代治疗局部枸橼酸抗凝与肝素抗凝不良事件的系统性评价及试验序贯分析

Adverse events with regional citrate anticoagulation versus heparin anticoagulation during continuous renal replacement therapy:a systematic review and trial sequential analysis

目的 应用Meta及试验序贯分析评价连续性肾脏替代治疗(continuous renal replacement therapy,CRRT)局部枸橼酸抗凝(regional citrate anticoagulation,RCA)与肝素抗凝的不良事件。方法 检索国内外数据库关于RCA与肝素抗凝在CRRT应用中的随机对照试验,不良事件包括低钙血症、代谢性酸中毒、代谢性碱中毒、出血、肝素诱导的血小板减少症中的任何一项。采用RevMan 5.2软件进行Meta分析,使用TSA 0.9软件进行试验序贯分析。结果 共检索791篇,最终纳入18篇研究。结果显示,与肝素抗凝相比,RCA总体不良事件发生风险减少46%(RR=0.54, 95%CI:0.35~0.82, P=0.004),其中出血发生风险减少73%(RR=0.27, 95%CI:0.19~0.38,P<0.001)。试验序贯分析表明,相比肝素抗凝,RCA总体不良事件及出血发生风险降低证据确切。结论 RCA总体不良事件发生风险较低,临床治疗安全性优于肝素抗凝,但RCA整体治疗方案有待进一步优化与改进。

Objective To compare adverse events(AEs)of regional citrate anticoagulation(RCA)versus heparin anticoagulation during continuous renal replacement therapy(CRRT)through systematic review and trial sequential analysis.Methods Based upon the relevant randomized control trials(RCT)comparing RCA and heparin anticoagulation during CRRT in both domestic and foreign databases,the authors re-analyzed various AEs including at least one of the following episodes:hypocalcemia,metabolic acidosis,metabolic alkalosis,hemorrhage and heparin-induced thrombocytopenia(HIT).Metaanalysis was performed with Revman 5.2 and TSA 0.9 software for trial sequential analysis(TSA).Results Among a total of 791 items,18 articles were included.As compared with heparin,RCA lowered the frequency of overall AEs(RR=0.54,95%CI:0.35-0.82,P=0.004).And hemorrhagic risk dropped by 73%(RR=0.27,95%CI:0.19-0.38,P<0.001).The above findings were further confirmed by TSA analysis.Conclusions As compared with heparin,the risks for overall AEs with RCA decline significantly.RCA is thus superior to heparin in term of anticoagulation safety during CRRT.However,therapeutic protocols of RCA should be further optimized.