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Response of erythropoiesis and iron metabolism to recombinant human erythropoietin in intensive care unit patients

van Iperen, Charlotte E., MD; Gaillard, Carlo A. J. M., MD, PhD; Kraaijenhagen, Rob J., PhD; Braam, Branko G., MD, PhD; Marx, Joannes J. M., MD, PhD; van de Wiel, Albert, MD, PhD

Clinical Investigations
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Objectives Critically ill patients often are anemic, which may impair oxygen delivery. Transfusion of red cells and supplementation with vitamins or iron are the usual therapeutic strategies, whereas only sporadic data are available on the use of epoetin alfa in these patients. We investigated endogenous erythropoietin (EPO) production and the response to epoetin alfa in anemic intensive care unit (ICU) patients.

Design Randomized, open trial.

Setting Multidisciplinary ICU in a single secondary care center.

Patients Thirty-six critically ill patients admitted to the ICU who became anemic (hemoglobin concentration, <11.2 g/dL or <12.1 g/dL in case of cardiac disease) were randomized to one of three study groups.

Interventions All patients received folic acid (1 mg) daily. The control group received no additional therapy, the iron group received 20 mg of iron saccharate intravenously (iv) daily for 14 days. The EPO group received iv iron and epoetin alfa (300 IU/kg) subcutaneously on days 1, 3, 5, 7, and 9.

Measurements and Main Results Blood and reticulocyte counts were measured daily for 22 days. Serum EPO, C-reactive protein, serum transferrin receptor, and iron variables were measured on days 0, 2, 6, 10, and 21. Blood loss and red cell transfusions were recorded.

Serum EPO concentrations were inappropriately low for the degree of anemia at baseline, with no difference between patients with and without renal failure. Exogenous administration of EPO increased EPO concentrations from 23 ± 13 to a maximum of 166 ± 98 units/L on day 10 (p < .05). Reticulocyte count increased exclusively in the EPO group from 56 ± 33 × 109/L to a maximum of 189 ± 97 on day 13 (p < .05). Serum transferrin receptor rose only in the EPO group from 3.7 ± 1.4 to 8.6 ± 3.1 mg/L on day 10 (p < .05) and remained elevated on day 21, indicating an increase in erythropoiesis. Hemoglobin concentration and platelet count remained identical in the three study groups.

Conclusion Endogenous EPO concentrations are low in critically ill patients. The bone marrow of these patients is able to respond to exogenous epoetin alfa, as shown by elevated concentrations of reticulocytes and serum transferrin receptors.

From the Departments of Internal Medicine and Intensive Care (Drs. van Iperen, Gaillard, and van de Wiel), Amersfoort, The Netherlands, and the Department of Internal Medicine (Drs. van Iperen and Braam and Prof. Dr. Marx), University Hospital Utrecht, Utrecht, The Netherlands.

The epoetin alfa used in this study was graciously provided by Janssen-Cilag (Tilburg, The Netherlands) and the VAMP system was provided by Baxter Healthcare (Utrecht, The Netherlands).

Presented, in part, at the meeting of the 7th World Congress of Intensive & Critical Care Medicine, June 29-July 3, 1997, Ottawa, Canada.

Copyright © by 2000 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.