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Erythropoietin in Critical Care Patients

Among all ICU patients, need for transfusion did not change when epoetin was administered; among trauma patients, epoetin increased the 140-day survival rate.

Major concerns have been expressed about use of erythropoietin in patients with anemia; these concerns culminated in warnings that advised limited use of the agent in patients who are at risk for thrombosis, such as those with cancer or heart disease. Many thought that this risk was incurred when erythropoietin was used to raise hemoglobin levels higher than 12 g/dL, but a new study suggests that thrombosis can occur even in patients whose target hemoglobin levels are lower than this value.

University-based investigators at 115 U.S. medical centers conducted a randomized, double-blind, placebo-controlled trial of erythropoietin in 1460 patients with hemoglobin concentrations lower than 12 g/dL who were admitted to medical or surgical intensive care units. Epoetin (40,000 IU weekly) was given for 3 weeks, unless hemoglobin levels exceeded 12 g/dL; patients also received oral or parenteral iron. Transfusions were given to maintain hemoglobin levels between 7 and 9 g/dL. Most patients were admitted to ICUs because of trauma or surgery; medical admissions constituted only 23% of patients.

Transfusions were required by 46% of patients in the epoetin group and by 48% of those in the placebo group, which was a nonsignificant difference. However, mean hemoglobin concentrations at day 29 increased more in the epoetin group than in the placebo group (by 1.58 vs. 1.20 g/dL; P<0.001), and a larger percentage of the epoetin patients than placebo patients were still alive at day 29 (62 vs. 83 deaths; P=0.02). The latter difference was due mostly to better survival among trauma patients who received epoetin; among trauma patients, significantly higher survival in the epoetin group persisted to day 140 (24 vs. 36 deaths). Improved survival with epoetin was offset by more thrombotic events: 120 patients in the epoetin group experienced adverse vascular events (mostly deep venous thrombosis or myocardial infarction) versus 83 in the placebo group (P=0.008). Patients who received three injections of epoetin were at greater risk than those who received only one or two. Administration of heparin was protective and attenuated the difference in thromboses between the groups.

Comment: This study shows that the administration of erythropoietin to anemic patients in ICUs does not decrease requisite transfusions but might improve survival of trauma patients. These seemingly disparate results might be explained by the ability of erythropoietin to ameliorate ischemia (Lancet 2005; 365:1890). Nevertheless, along with findings from past studies, these show that erythropoietin heightens risk for adverse vascular events, even when hemoglobin levels are lower than 12 g/dL. Therefore, prescribing concomitant anticoagulant prophylaxis is appropriate whenever erythropoietin is given in the inpatient setting.

— David Green, MD, PhD

Published in Journal Watch Oncology and Hematology September 5, 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.

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