Laupland Kevin B, Kirkpatrick Andrew W, Delaney Anthony
Department of Critical Care Medicine, University of Calgary, Calgary, AB, Canada.
Crit Care Med. 2007 Dec;35(12):2686-92.
To systematically review the literature to assess whether adjunctive therapy with polyclonal intravenous immunoglobulin (ivIg) reduces mortality among critically ill adults with severe sepsis and septic shock.
MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials databases; the meta-register of controlled trials; and the Medical Editors Trial Amnesty register.
Prospective randomized clinical trials (RCTs) evaluating ivIg treatment in critically ill adults with severe sepsis or septic shock were included. Two reviewers conducted assessment of suitability for inclusion.
Two authors independently determined the validity of included studies and extracted data.
The effect of ivIg on all-cause mortality was quantified using a fixed-effect meta-analysis.
Fourteen RCTs published between 1988 and 2006 were included. Most were small, used relatively low doses of ivIg, and included predominantly surgical patients with Gram-negative infections. There was a significant reduction in mortality associated with use of ivIg treatment with a pooled odds ratio of 0.66 (95% confidence interval 0.53-0.83; p < .0005). In general, a greater treatment effect was seen among studies of lower methodological quality, studies using higher doses of ivIg, and studies that did not use albumin as a control. There was evidence of between-study heterogeneity (chi-square p = .009), and this was at least moderate as measured by the I2 value (I2 = 53.8%). When only high-quality studies were pooled, the odds ratio for mortality was 0.96 (95% confidence interval 0.71-1.3; p = .78).
This meta-analysis demonstrates an overall reduction in mortality with the use of ivIg for the adjunctive treatment of severe sepsis and septic shock in adults, although significant heterogeneity exists among the included trials and this result was not confirmed when only high-quality studies were analyzed. These data warrant a well-designed, adequately powered, and transparently reported clinical trial.
系统回顾文献，评估多克隆静脉注射免疫球蛋白（ivIg）辅助治疗是否能降低重症脓毒症和脓毒性休克成年患者的死亡率。
MEDLINE、EMBASE和Cochrane对照试验中央注册数据库；对照试验的元注册库；以及医学编辑试验特赦注册库。
纳入评估ivIg治疗重症脓毒症或脓毒性休克成年患者的前瞻性随机临床试验（RCT）。两名研究者对纳入的适用性进行评估。
两名作者独立确定纳入研究的有效性并提取数据。
使用固定效应荟萃分析量化ivIg对全因死亡率的影响。
纳入了1988年至2006年间发表的14项RCT。大多数研究规模较小，使用的ivIg剂量相对较低，主要纳入患有革兰氏阴性菌感染的外科患者。使用ivIg治疗可显著降低死亡率，合并比值比为0.66（95%置信区间0.53 - 0.83；p <.0005）。总体而言，在方法学质量较低的研究、使用较高剂量ivIg的研究以及未使用白蛋白作为对照的研究中，观察到更大的治疗效果。有证据表明研究间存在异质性（卡方检验p =.009），根据I²值衡量，这种异质性至少为中度（I² = 53.8%）。仅汇总高质量研究时，死亡率的比值比为0.96（95%置信区间0.71 - 1.3；p =.78）。
这项荟萃分析表明，使用ivIg辅助治疗成年重症脓毒症和脓毒性休克患者可总体降低死亡率，尽管纳入的试验之间存在显著异质性，且仅分析高质量研究时这一结果未得到证实。这些数据需要进行精心设计、有足够效力且报告透明的临床试验。
