万古霉素与肝事件风险Meta分析

Risk of Hepatic Events in Patients Treated with Vancomycin: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

目的对已经发表的万古霉素与肝事件风险随机对照临床试验进行Meta分析,探讨万古霉素与肝事件风险的关系。方法全面搜索和审查被MEDLINE、PubMed、国际药学文摘和Cochrane图书馆收录的从1950年1月—2010年6月发表的使用万古霉素联合或不联合其他治疗与非万古霉素治疗报告肝事件的随机对照研究论文,并提取和审查数据。对选定的研究用Jadad评分法进行评估,影响的大小用95%CI风险比(RR)和NNH表示,发表偏倚的影响用漏斗图和Egger's检验评估。结果 20个随机对照试验,共7419例病例符合研究纳入标准。接受万古霉素治疗的患者肝事件特别是血清转氨酶水平升高的发生率高于接受非万古霉素治疗组(汇集RR=1.95;95%CI 1.62,2.36;P<0.001),但大部分风险事件是轻至中度。肝事件报告明显增加与发表偏倚无明显相关。结论建议对使用万古霉素的患者进行肝事件风险的连续监测。

Objective To conduct a meta-analysis of published randomized controlled clinical trials （RCTs） and to explore the relationship of vancomycin in an increased risk of hepatic events. Methods A comprehensive search and review of published clinical studies indexed in MEDLINE, PubMed, International Pharmaceutical Abstracts and the Cochrane Library during January 1950 and June 2010 were conducted. The inclusion criteria consisted of （i） published RCTs comparing vancomycin with/without other additional treatment to other non-vancomycin treatment regimes ; and （ii） studies that reported hepatic events. The data related to any hepatic events reported in RCTs were extracted and exam- ined. The quality of selected studies was assessed based on the Jadad scale. The effect size was presented as a risk ratio （RR） with a 95% CI and number needed to harm （NNH）. The pooled RRs were calculated by using both fixed-effects and random-effects models. The impact of publication bias was assessed by funnel plot and the Egger＇s test. Results A total of 20 RCTs, including 7419 patients, met the study inclusion criteria and were selected. An increased incidence of hepatic events, specifically elevated serum aminotransferase levels, was observed in patients receiving vancomycin, when compared with the controls （ pooled RR = 1.95 ; 95% CI 1.62, 2.36 ; P 〈 0. 001 ） , but the majority of the events were mild to moderate in nature. No evidence is currently available suggesting that the use of vancomcycin confers a risk of progressive or severe druginduced liver injury. Conclusion Continuous monitoring of hepatic events on a routine basis among patients with the use of vancomycin is suggested.