Use of Epoetin Alpha in Critically Ill Patients. Sept 10th, 2007.

September 10th, 2007 By Farhad Abtahian, M.D. Ph.D. [mailto:fabtahian@partners.org]

Anemia is a common problem among patients in the ICU yet studies have shown that red blood cell (RBC) transfusions may actually increase mortality in these patients. Corwin et al hypothesized that the use of epoetin alpha could reduce the incidence and severity of anemia in ICU patients and therefore decrease the use of RBC transfusions. In a prospective, randomized, placebo-controlled trial published in The New England Journal of Medicine, they show that the use of epoetin alpha does not reduce the use of red-cell transfusion but does result in a trend toward reduced mortality.

In an industry-sponsored study, 1460 patients admitted into ICUs were randomized to receive either epoetin alpha or placebo for 3 weeks and followed for 140 days. The primary end point in the study was the percent of patients receiving RBC transfusion and the secondary ends points were mortality, number of transfused units, and change in hemoglobin concentration from baseline.

Surprisingly, there was no difference between the epoetin alpha and placebo group in number of patients receiving blood transfusion and the total number of units transfused. The most likely explanation for the failure to reduce the number of patients receiving transfusions is a change in transfusion practice with the level of hemoglobin triggering transfusion lower now than in the past. Still, the use of epoetin alpha was associated with reduced mortality at day 29 (8.5% vs 11.4%, P=0.02). In a pre-specified subgroup analysis, epoetin alpha resulted in a significant reduction in mortality in trauma patients (3.5% vs 6.6%, P=0.04), but not surgical or medical patients. At 140 days there was a trend toward reduced mortality among patients receiving epoetin. As for adverse events, the use of epoetin resulted in an increase in the number of thrombotic vascular events.

This study confirms previous studies showing a mortality benefit with epoetin use in trauma patients but not surgical and medical ICU patients (although the study may have been underpowered for non-traumatic patients). This study was driven by the hypothesis that epoetin alpha use would decrease mortality and morbidity by reducing the need for RBC transfusion and the consequential adverse effects. There was, however, no reduction in the number of patients receiving transfusion and the total number of units transfused. Since there still was a mortality benefit among at least a subset of patients, this study raised the possibility of nonhematopoietic benefits associated with epoetin use. Over all, these results cannot justify the use of epoetin alpha in critically ill medical and surgical patients although the trends seen in mortality necessitate further study.


 * 1) ref1 pmid=17804841