枸橼酸和肝素封管液预防血液透析长期留置导管相关感染的Meta分析

Citrate lock versus heparin lock for the prevention of catheter related infections in hemodialysis patients with tunneled catheters： a Meta-analysis of randomized controlled trials

目的探究在使用长期留置导管的透析患者中，枸橼酸封管液是否在预防导管相关感染、出血并发症、导管功能障碍等方面优于传统肝素封管液。方法检索Pubmed、the Cochrane Library、EMBASE、Ovid、万方、维普、CNKI、CBM等数据库和相关杂志中符合纳入标准的随机对照试验，并使用Revman5．0和STATA10．0软件进行Meta分析。研究终点指标包括导管相关感染、出血、溶栓治疗次数、功能障碍所致拔管、血栓形成、全因死亡率。结果共纳入15篇随机对照试验（1621例患者），其中8篇研究比较单纯枸橼酸封管液与肝素封管液的差异，其他7篇研究则关注枸橼酸和其他抗菌药物的复合配方封管液。Meta分析结果显示，使用枸橼酸封管的患者发生导管相关感染的概率较使用肝素封管的患者下降了47％，差异有统计学意义（RR=0．53，95％CI0．36—0．77．P〈0．01）。按照封管液配方进行亚组分析发现，各类含抗菌药物的复合枸橼酸封管液（枸橼酸＋庆大霉素、枸橼酸＋牛磺罗定、枸橼酸＋亚甲基蓝＋羟苯甲酯＋羟苯丙酯）预防导管相关感染的效果均优于传统肝素封管液（P分别为O．01、0．04、0．01）；单纯枸橼酸封管组的导管相关感染风险虽然低于肝素组（RR=0．68），但差异尚无统计学意义（95％CI0．38—1．21，P=0．19）。枸橼酸组患者出血并发症显著少于肝素组（RR=O．53，95％CI0．34—0．84，P〈0．01），而两组在溶栓治疗次数（P=0．93）、功能障碍所致拔管（P=0．35）、血栓形成（P=O．64）、全因死亡率（P=0．35）等方面差异均无统计学意义。结论枸橼酸联用抗菌药物封管可降低长期留置导管相关感染风险，而单用枸橼酸封管与使用肝素封管的差异无统计学意义。枸橼酸封管液在控制出血并发症方面优于肝素，预防导管功能障碍的效果与肝素类似。

Objective To study whether citrate lock is superior to heparin lock in the prevention of catheter related infections, bleeding complications and catheter malfunctions among hemodialysis patients with tunneled catheters. Methods By searching in Pubmed, the Cochrane Library, EMBASE, Ovid, WanFang, VIP, CNKI and CBM databases as well as related journals, qualified randomized controlled trials were included in a Meta- analysis using Revman 5.0 and STATA 10.0 software. The endpoints included catheter related infection, bleeding complication, thrombolytic treatment, catheter removal for malfunction, catheter thrombosis and all- cause death. Results Fifteen randomized controlled trials were included with 1621 patients involved. Eight studies compared citrate alone with heparin lock, while 7 trials focuscd on citrate in combinatioll with other antimicrobials. Pooled analysis demonstrated that incidence of catheter related infections in patients receiving citrate lock decreased by 47% compared with those on heparin （RR=0.53, 95%CI0.36-0.77, P 〈 0.01）. Subgroup analysis by types of citrate lock indicated that all combined lock solutions of citrate and other antimicrobials （citrate ＋ gentamicin, citrate ＋ taurolidine, citrate ＋ methylene blue ＋ methylparaben ＋ propylparaben） were superior to heparin lock in preventing catheter-related infections （P = 0.01, 0.04, 0.01, respectively）; citrate alone seemed to reduce catheter-related infection risk （RR = 0.68）, but no statistically significant difference was observed （95%CI 0.38- 1.21, P = 0.19）. There were fewer patients with bleeding complications in citrate group （RR = 0.53, 95% CI 0.34 - 0.84, P 〈 0.01）, while citrate showed no advantage over heparin lock in terms of thrombolytic treatment （P = 0.93）, catheter removal for malfunction （P = 0.35）, catheter thrombosis （P = 0.64） and all- cause death （P = 0.35）. Conclusions For hemodialysis patients with tunneled catheters, combined lock solutions of citrate and other antimicrobials, rather than citrate alone, are superior to heparin in preventing catheter related infections. Citrate locks are associated with less bleeding complications, and are comparable to heparin in the maintenance of catheter patency.