Cell-free hemoglobin-based blood substitutes and risk of myocardial infarction and death: a meta-analysis.

Abstract

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 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.

• Authors: Charles Natanson, Steven J Kern, Peter Lurie, Steven M Banks, Sidney M Wolfe
• Journal: JAMA (JAMA) Vol. 299 Issue 19 Pg. 2304-12 (May 21 2008) ISSN: 1538-3598 [Electronic] United States
• PMID: 18443023 (Publication Type: Journal Article, Meta-Analysis, Research Support, N.I.H., Extramural)

Chemical References

• Blood Substitutes
• Hemoglobins
• O-raffinose cross-linked human hemoglobin
• PolyHeme
• HBOC 201
• Raffinose

Topics

• Blood Substitutes (adverse effects)
• Hemoglobins (adverse effects)
• Humans
• Mortality
• Myocardial Infarction (epidemiology)
• Raffinose (adverse effects, analogs & derivatives)
• Risk