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Erythropoietin in the ICU — Mixed Results

It lowered mortality in trauma patients but increased risk for thrombotic events.

In a previous trial (Journal Watch Jan 3 2003), erythropoietin decreased transfusions but not mortality in adult intensive care unit patients with hematocrits lower than 38%. Now, the same researchers have conducted another randomized trial funded by the drug manufacturer in 1460 patients with hemoglobin levels below 12 g/dL who were expected to stay in the ICU for at least several days. Among many exclusion criteria were coronary ischemia and history of thrombotic events.

Patients received epoetin alfa (40,000 U) or placebo weekly for 3 weeks when hemoglobin concentrations were below 12 g/dL. Need for transfusion was determined by each patient’s physician. Epoetin alfa did not decrease the number of transfusions, but it did raise mean hemoglobin level slightly (by 0.4 g/dL compared with placebo at 4 weeks). In an analysis of prespecified subgroups, 4-week mortality was significantly lower with epoetin alfa than with placebo among trauma patients (3.5% vs. 6.6%) but not among other surgical or medical patients. Epoetin alfa recipients were more likely to have a thrombotic venous or arterial vascular event than placebo recipients (16.5% vs. 11.5%).

Comment: Erythropoietin lowered mortality in one subgroup of critically ill patients (trauma patients), but it increased overall risk for thrombotic events. To explain a mortality benefit despite no difference in transfusions and only a small increase in hemoglobin levels, the authors speculate that nonhematopoietic effects of erythropoietin (e.g., protecting cells from hypoxemia and ischemia) might play a role. However, editorialists argue that these results should not change practice, in part because other recent studies have shown increased mortality associated with erythropoietin in certain subgroups of patients with renal failure or cancer.

Allan S. Brett, MD

Published in Journal Watch General Medicine September 6, 2007

Citation(s):

Corwin HL et al. Efficacy and safety of epoetin alfa in critically ill patients. N Engl J Med 2007 Sep 6; 357:965-76.

Cook D and Crowther M. Targeting anemia with erythropoietin during critical illness. N Engl J Med 2007 Sep 6; 357:1037-9.

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