TY - JOUR
T1 - Cell-free hemoglobin-based blood substitutes and risk of myocardial infarction and death
T2 - A meta-analysis
AU - Natanson, Charles
AU - Kern, Steven J.
AU - Lurie, Peter
AU - Banks, Steven M.
AU - Wolfe, Sidney M.
PY - 2008/5/21
Y1 - 2008/5/21
N2 - 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≥.60), and data were combined using a fixed-effects model. Overall, there was a statistically significant increase in the risk of death (164 deaths in the HBBS-treated groups and 123 deaths in the control groups; relative risk [RR], 1.30; 95% confidence interval [CI], 1.05-1.61) and risk of MI (59 MIs in the HBBS-treated groups and 16 MIs in the control groups; RR, 2.71; 95% CI, 1.67-4.40) with these HBBSs. Subgroup analysis of these trials indicated the increased risk was not restricted to a particular HBBS or clinical indication. Conclusion: Based on the available data, use of HBBSs is associated with a significantly increased risk of death and MI.
AB - 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≥.60), and data were combined using a fixed-effects model. Overall, there was a statistically significant increase in the risk of death (164 deaths in the HBBS-treated groups and 123 deaths in the control groups; relative risk [RR], 1.30; 95% confidence interval [CI], 1.05-1.61) and risk of MI (59 MIs in the HBBS-treated groups and 16 MIs in the control groups; RR, 2.71; 95% CI, 1.67-4.40) with these HBBSs. Subgroup analysis of these trials indicated the increased risk was not restricted to a particular HBBS or clinical indication. Conclusion: Based on the available data, use of HBBSs is associated with a significantly increased risk of death and MI.
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U2 - 10.1001/jama.299.19.jrv80007
DO - 10.1001/jama.299.19.jrv80007
M3 - Review article
C2 - 18443023
AN - SCOPUS:44249093233
SN - 0098-7484
VL - 299
SP - 2304
EP - 2312
JO - JAMA
JF - JAMA
IS - 19
ER -