BMJ：羟乙基淀粉不能给败血症患者带来临床获益

在2013年2月15日出版的《英国医学杂志》(British Medical Journal)上，发表了丹麦哥本哈根大学Nicolai Haase等人的一项研究结果，该研究对羟乙基淀粉130/0.38-0.45与晶体或白蛋白输液治疗对败血症患者死亡率、肾脏损伤、出血及严重不良事件的影响进行对比评价。

该研究主要针对相关随机临床试验荟萃分析及试验序贯分析进行了系统性考察该研究相关数据来自于Cochrane Library、 Medline、Embase、Biosis Previews、Science Citation Index Expanded、CINAHL、Current Controlled Trials、Clinicaltrials.gov、及Centerwatch等，数据截止时期为2012年9月；研究人员对参考文献列表及其他系统综述进行了手工检索，并联系了相关研究作者及制药企业。

纳入该研究的临床试验为，对比考察羟乙基淀粉130/0.38-0.45与晶体或人白蛋白治疗败血症患者的随机临床试验。纳入研究包括已发表及未发表的临床试验，并无语言及预定义结果限制。有两位评审者就方法、干预、结局及偏倚风险对相关研究的纳入及数据提取进行了独立评价。研究人员通过固定效应模型机随机效应模型，对95%置信区间的风险比及平均差异进行了测算。

该研究最终纳入了包括3456例败血症随机患者的9项试验。整体而言，羟乙基淀粉130/0.38-0.45及晶体或白蛋白对相对死亡风险并无影响(1.04, 95% 置信区间 0.89至1.22, 3414 例患者, 8项试验)，在低偏倚风险的预定义分析中，相对死亡风险为1.11 (1.00 至1.23, 试验序贯分析 (TSA)校正后95%置信区间 0.95至1.29, 3016例患者, 4项试验)。羟乙基淀粉组中，肾脏替代疗法使用率较高(1.36, 1.08 至1.72, TSA 校正后1.03至1.80, 1311例患者, 5项试验)，急性肾损伤相对风险为1.18 (0.99至1.40, TSA校正后0.90至1.54, 994例患者, 4项试验)。羟乙基淀粉组中输注红细胞的患者较多(1.29, 1.13至1.48, TSA 校正后1.10至1.51, 973例患者, 3项试验)，且出现严重不良事件的患者较多(1.30, 1.02至1.67, TSA校正后0.93至1.83, 1069例患者, 4项试验)。组间红细胞输注量并无差异(平均差值为 65 mL, 95% 置信区间 -20 至149 mL, 3项试验)。

研究人员根据对近期临床试验数据进行的常规荟萃分析认为，与晶体或白蛋白相比，羟乙基淀粉130/0.38-0.45增加了肾脏替代疗法及红细胞输注的使用频率，且导致败血症患者发生更多的不良事件。这似乎表明，羟乙基淀粉130/0.38-0.45并不能为败血症患者带来整体临床获益。

与败血症相关的拓展阅读： 

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Hydroxyethyl starch 130/0.38-0.45 versus crystalloid or albumin in patients with sepsis: systematic review with meta-analysis and trial sequential analysis
Objective
To assess the effects of fluid therapy with hydroxyethyl starch 130/0.38-0.45 versus crystalloid or albumin on mortality, kidney injury, bleeding, and serious adverse events in patients with sepsis.
Design
Systematic review with meta-analyses and trial sequential analyses of randomised clinical trials.
Data sources
Cochrane Library, Medline, Embase, Biosis Previews, Science Citation Index Expanded, CINAHL, Current Controlled Trials, Clinicaltrials.gov, and Centerwatch to September 2012; hand search of reference lists and other systematic reviews; contact with authors and relevant pharmaceutical companies.
Study selection
Eligible trials were randomised clinical trials comparing hydroxyethyl starch 130/0.38-0.45 with either crystalloid or human albumin in patients with sepsis. Published and unpublished trials were included irrespective of language and predefined outcomes.
Data extraction
Two reviewers independently assessed studies for inclusion and extracted data on methods, interventions, outcomes, and risk of bias. Risk ratios and mean differences with 95% confidence intervals were estimated with fixed and random effects models.
Results
Nine trials that randomised 3456 patients with sepsis were included. Overall, hydroxyethyl starch 130/0.38-0.45 versus crystalloid or albumin did not affect the relative risk of death (1.04, 95% confidence interval 0.89 to 1.22, 3414 patients, eight trials), but in the predefined analysis of trials with low risk of bias the relative risk of death was 1.11 (1.00 to 1.23, trial sequential analysis (TSA) adjusted 95% confidence interval 0.95 to 1.29, 3016 patients, four trials). In the hydroxyethyl starch group, renal replacement therapy was used more (1.36, 1.08 to 1.72, TSA adjusted 1.03 to 1.80, 1311 patients, five trials), and the relative risk of acute kidney injury was 1.18 (0.99 to 1.40, TSA adjusted 0.90 to 1.54, 994 patients, four trials). More patients in the hydroxyethyl starch group were transfused with red blood cells (1.29, 1.13 to 1.48, TSA adjusted 1.10 to 1.51, 973 patients, three trials), and more patients had serious adverse events (1.30, 1.02 to 1.67, TSA adjusted 0.93 to 1.83, 1069 patients, four trials). The transfused volume of red blood cells did not differ between the groups (mean difference 65 mL, 95% confidence interval −20 to 149 mL, three trials).
Conclusion
In conventional meta-analyses including recent trial data, hydroxyethyl starch 130/0.38-0.45 versus crystalloid or albumin increased the use of renal replacement therapy and transfusion with red blood cells, and resulted in more serious adverse events in patients with sepsis. It seems unlikely that hydroxyethyl starch 130/0.38-0.45 provides overall clinical benefit for patients with sepsis