Cell-Free Hemoglobin-Based Blood Substitutes and Risk of Myocardial Infarction and Death

作者：Charles Natanson, Steven J. Kern, Peter G. Lurie, Steven M. Banks, Sidney M. Wolfe · 发表于：JAMA · 年份：2008 · DOI：10.1001/jama.299.19.jrv80007 · 被引用次数：620 · 研究领域：Hemoglobin structure and function、Blood transfusion and management、Trauma, Hemostasis, Coagulopathy, Resuscitation

CONTEXT: Hemoglobin-based blood substitutes (HBBSs) are infusible oxygen-carrying liquids that have long shelf lives, have no need for refrigeration or cross-matching, and are ideal for treating hemorrhagic shock in remote settings. Some trials of HBBSs during the last decade have reported increased risks without clinical benefit. OBJECTIVE: To assess the safety of HBBSs in surgical, stroke, and trauma patients. DATA SOURCES: PubMed, EMBASE, and Cochrane Library searches for articles using hemoglobin and blood substitutes from 1980 through March 25, 2008; reviews of Food and Drug Administration (FDA) advisory committee meeting materials; and Internet searches for company press releases. STUDY SELECTION: Randomized controlled trials including patients aged 19 years and older receiving HBBSs therapeutically. The database searches yielded 70 trials of which 13 met these criteria; in addition, data from 2 other trials were reported in 2 press releases, and additional data were included in 1 relevant FDA review. DATA EXTRACTION: Data on death and myocardial infarction (MI) as outcome variables. RESULTS: Sixteen trials involving 5 different products and 3711 patients in varied patient populations were identified. A test for heterogeneity of the results of these trials was not significant for either mortality or MI (for both, I2 = 0%, P > or = .60), and data were combined using a fixed-effects model. Overall, there was a statistically significant increase in the risk of death (164 d...