Department of Emergency Medicine, General Hospital, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria.
Intensive Care Med. 2013 Nov;39(11):1896-908. doi: 10.1007/s00134-013-3030-9. Epub 2013 Aug 9.
Erythropoiesis stimulating agents (ESAs) are used to treat anemia in critically ill patients. This indication is off-label, because it is not licensed by regulatory authorities. Recently ESAs were suspected to harm critically ill patients. Our objective was to assess the safety of ESAs in off-label indications in critically ill patients.
Eleven databases were searched up to April 2012. We considered randomized controlled trials (RCTs) and controlled observational studies in any language that compared off-label ESAs treatment with other effective interventions, placebo or no treatment in critically ill patients. Two authors independently screened and evaluated retrieved records, extracted data and assessed risk of bias and quality of reporting.
We used frequentist and Bayesian models to combine studies, and performed sensitivity and subgroup analyses. From 12,888 citations, we included 48 studies (34 RCTs; 14 observational), involving 944,856 participants. Harm reporting was of medium to low quality. There was no statistically significant increased risk of adverse events in general, serious adverse events, the most frequently reported adverse events, and death in critically ill patients treated with ESAs. These results were robust against risk of bias and analysis methods. There is evidence that ESAs increase the risk of clinically relevant thrombotic vascular events, and there is some less certain evidence that ESAs might increase the risk for venous thromboembolism.
In critically ill patients, administration of ESAs is associated with a significant increase in clinically relevant thrombotic vascular events but not with other frequently reported adverse events and death.
促红细胞生成素（EPO）被用于治疗危重病患者的贫血。该适应证为超适应证使用，因为它未被监管机构批准。最近有研究怀疑 EPO 会对危重病患者造成伤害。我们的目的是评估 EPO 在危重病患者超适应证使用的安全性。
我们检索了截至 2012 年 4 月的 11 个数据库。我们考虑了比较 EPO 超适应证治疗与其他有效干预、安慰剂或无治疗的在任何语言发表的随机对照试验（RCT）和对照观察性研究。两位作者独立筛选和评估了检索记录、提取数据，并评估了偏倚风险和报告质量。
我们使用了经典和贝叶斯模型来合并研究，并进行了敏感性和亚组分析。从 12888 条引用中，我们纳入了 48 项研究（34 项 RCT；14 项观察性研究），涉及 944856 名参与者。不良事件报告的质量为中等到低等。与接受 EPO 治疗的危重病患者的一般不良事件、严重不良事件、最常报告的不良事件和死亡风险增加无统计学意义。这些结果在偏倚风险和分析方法方面是稳健的。有证据表明 EPO 增加了临床相关的血栓性血管事件的风险，并且有一些不太确定的证据表明 EPO 可能增加静脉血栓栓塞的风险。
在危重病患者中，EPO 的给药与临床相关的血栓性血管事件显著增加相关，但与其他常报告的不良事件和死亡无关。
