Efficacy of Recombinant Human Erythropoietin in Critically Ill Patients: A Randomized Controlled Trial | Critical Care Medicine | JAMA | JAMA Network
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1.
Spence RK, Cernaianu AC, Carson J, DelRossi AJ. Transfusion and surgery.  Curr Probl Surg.1993;30:1101-1180.Google Scholar
2.
Littenberg B, Corwin H, Gettinger A, Leichter J, AuBuchon J. A practice guideline and decision aid for blood transfusion.  Immunohematology.1995;11:88-92.Google Scholar
3.
Corwin HC, Parsonnet KC, Gettinger A. RBC transfusion in the ICU: is there a reason?  Chest.1995;108:767-771.Google Scholar
4.
Groeger JS, Guntupalli KK, Strosberg M.  et al.  Descriptive analysis of critical care units in the United States: patient characteristics and intensive care unit utilization.  Crit Care Med.1993;21:279-291.Google Scholar
5.
Vincent JL, Baron JF, Gattinoni L.  et al.  Anemia and blood transfusion in critically ill patients.  JAMA.2002;288:1499-1507.Google Scholar
6.
Corwin HL, Abraham E, Fink MP.  et al.  Anemia and blood transfusion in the critically ill: current clinical practice in the US—The CRIT Study [abstract].  Crit Care Med.2001;29(suppl):A2.Google Scholar
7.
Goodnough LT, Brecher ME, Kanter MH, AuBuchon JP. Transfusion medicine: first of two parts—blood transfusion.  N Engl J Med.1999;340:438-447.Google Scholar
8.
Blumberg N, Heal JM. Effects of transfusion on immune function: cancer recurrence and infection.  Arch Pathol Lab Med.1994;118:371-379.Google Scholar
9.
Landers DF, Hill GE, Wong KC, Fox IJ. Blood transfusion-induced immunomodulation.  Anesth Analg.1996;82:187-204.Google Scholar
10.
Mickler TA, Longnecker DE. The immunosuppressive aspects of blood transfusion.  J Intensive Care Med.1992;7:176-188.Google Scholar
11.
Marik PE, Sibbald WJ. Effect of stored-blood transfusion on oxygen delivery in patients with sepsis.  JAMA.1993;269:3024-3029.Google Scholar
12.
Fitzgerald RD, Martin CM, Dietz GE, Doig GS, Potter RF, Sibbald WJ. Transfusing red blood cells stored in citrate phosphate dextrose adenine-1 for 28 days fails to improve tissue oxygenation in rats.  Crit Care Med.1997;25:726-732.Google Scholar
13.
Hebert PC, Wells G, Blajchman MA.  et al. for the Transfusion Requirements in Critical Care Investigators, Canadian Critical Care Trials Group.  A multicenter, randomized, controlled clinical trial of transfusion requirements in critical care.  N Engl J Med.1999;340:409-417.Google Scholar
14.
Corwin HL, Krantz S. Anemia in the critically ill: "acute" anemia of chronic disease.  Crit Care Med.2000;28:3098-3099.Google Scholar
15.
Rodriguez RM, Corwin HL, Gettinger A, Corwin MJ, Gubler D, Pearl RG. Nutritional deficiencies and blunted erythropoietin response as causes of the anemia of critical illness.  J Crit Care.2001;16:36-41.Google Scholar
16.
Rogiers P, Zhang H, Leeman M.  et al.  Erythropoietin response is blunted in critically ill patients.  Intensive Care Med.1997;23:159-162.Google Scholar
17.
Krafte-Jacobs B, Levetown ML, Bray GL, Ruttimann UE, Pollack MM. Erythropoietin response to critical illness.  Crit Care Med.1994;22:821-826.Google Scholar
18.
Frede S, Fandrey J, Pagel H, Hellwig T, Jelkmann W. Erythropoietin gene expression is suppressed after lipopolysaccharide or interleukin-1 beta injections in rats.  Am J Physiol.1997;273:R1067-R1071.Google Scholar
19.
Jelkmann W. Proinflammatory cytokines lowering erythropoietin production.  J Interferon Cytokine Res.1998;18:555-559.Google Scholar
20.
Corwin HL, Gettinger A, Rodriguez RM.  et al.  Efficacy of recombinant human erythropoietin in the critically ill patient: a randomized double-blind placebo-controlled trial.  Crit Care Med.1999;27:2346-2350.Google Scholar
21.
Goldberg MA, McCutchen JW, Jove M.  et al.  A safety and efficacy comparison study of two dosing regimens of epoetin alpha in patients undergoing major orthopedic surgery.  Am J Orthop.1996;25:544-552.Google Scholar
22.
Monk TG, Goodnough LT, Brecher ME, Colberg JW, Andriole GL, Catalona WJ. A prospective randomized comparison of three blood conservation strategies for radical prostatectomy.  Anesthesiology.1999;91:24-33.Google Scholar
23.
Qvist N, Boesby S, Wolff B, Hansen CP. Recombinant human erythropoietin and hemoglobin concentration at operation and during the postoperative period: reduced need for blood transfusions in patients undergoing colorectal surgery—prospective double-blind placebo-controlled study.  World J Surg.1999;23:30-35.Google Scholar
24.
Gabrilove JL, Cleeland CS, Livingston RB, Sarokhan B, Winer E, Einhorn LH. Clinical evaluation of once-weekly dosing of epoetin alfa in chemotherapy patients: improvements in hemoglobin and quality of life are similar to three-times weekly dosing.  J Clin Oncol.2001;19:2875-2882.Google Scholar
25.
Goodnough LT, Johnston MF, Toy PT.for the Transfusion Medicine Academic Award Group.  The variability of transfusion practice in coronary artery bypass surgery.  JAMA.1991;265:86-90.Google Scholar
26.
Hebert PC, Yetisir E, Martin C.  et al.  Is a low transfusion threshold safe in critically ill patients with cardiovascular diseases?  Crit Care Med.2001;29:227-234.Google Scholar
27.
Casadevall N, Nataf J, Viron B.  et al.  Pure red-cell aplasia and antierythropoietin antibodies in patients treated with recombinant erythropoietin.  N Engl J Med.2002;346:469-475.Google Scholar
28.
Casadevall N. Antibodies against rHuEPO: native and recombinant.  Nephrol Dial Transplant.2002;17 Suppl 5:42-47.Google Scholar
29.
McRae AD, Weijer C. Lessons from everyday lives: a moral justification for acute care research.  Crit Care Med.2002;30:1146-1151.Google Scholar
30.
Burck R. Minimal risk: the debate goes on.  Crit Care Med.2002;30:1180-1181.Google Scholar
31.
Myhre BA, McRuer D. Human error: a significant cause of transfusion mortality.  Transfusion.2000;40:879-885.Google Scholar
32.
Spahn DR, Casutt M. Eliminating blood transfusions: new aspects and perspectives.  Anesthesiology.2000;93:242-255.Google Scholar
Original Contribution
December 11, 2002

Efficacy of Recombinant Human Erythropoietin in Critically Ill Patients: A Randomized Controlled Trial

Author Affiliations

Author Affiliations: Critical Care Medicine (Dr H. Corwin) and Department of Anesthesiology (Dr Gettinger), Dartmouth-Hitchcock Medical Center, Lebanon, NH; Department of Anesthesia, Stanford University Medical Center, Stanford, Calif (Dr Pearl); Department of Critical Care Medicine, University of Pittsburgh Medical Center, Pittsburgh, Pa (Dr Fink); Rhode Island Hospital, Providence (Dr Levy); St Louis University Health Science Center, St Louis, Mo (Dr Shapiro); and Department of Pediatrics, Boston University School of Medicine (Dr M. Corwin), Department of Epidemiology, Boston University School of Public Health (Dr Colton), and CareStat Inc (Drs M. Corwin and Colton), Boston, Mass.

JAMA. 2002;288(22):2827-2835. doi:10.1001/jama.288.22.2827
Abstract

Context Anemia is common in critically ill patients and results in a large number of red blood cell (RBC) transfusions. Recent data have raised the concern that RBC transfusions may be associated with worse clinical outcomes in some patients.

Objective To assess the efficacy in critically ill patients of a weekly dosing schedule of recombinant human erythropoietin (rHuEPO) to decrease the occurrence of RBC transfusion.

Design A prospective, randomized, double-blind, placebo-controlled, multicenter trial conducted between December 1998 and June 2001.

Setting A medical, surgical, or a medical/surgical intensive care unit (ICU) in each of 65 participating institutions in the United States.

Patients A total of 1302 patients who had been in the ICU for 2 days and were expected to be in the ICU at least 2 more days and who met eligibility criteria were enrolled in the study; 650 patients were randomized to rHuEPO and 652 to placebo.

Intervention Study drug (40 000 units of rHuEPO) or placebo was administered by subcutaneous injection on ICU day 3 and continued weekly for patients who remained in the hospital, for a total of 3 doses. Patients in the ICU on study day 21 received a fourth dose.

Main Outcome Measures The primary efficacy end point was transfusion independence, assessed by comparing the percentage of patients in each treatment group who received any RBC transfusion between study days 1 and 28. Secondary efficacy end points identified prospectively included cumulative RBC units transfused per patient through study day 28; cumulative mortality through study day 28; change in hemoglobin from baseline; and time to first transfusion or death.

Results Patients receiving rHuEPO were less likely to undergo transfusion (60.4% placebo vs 50.5% rHuEPO; P<.001; odds ratio, 0.67; 95% confidence interval [CI], 0.54-0.83). There was a 19% reduction in the total units of RBCs transfused in the rHuEPO group (1963 units for placebo vs 1590 units for rHuEPO) and reduction in RBC units transfused per day alive (ratio of transfusion rates, 0.81; 95% CI, 0.79-0.83; P = .04). Increase in hemoglobin from baseline to study end was greater in the rHuEPO group (mean [SD], 1.32 [2] g/dL vs 0.94 [1.9] g/dL; P<.001). Mortality (14% for rHuEPO and 15% for placebo) and adverse clinical events were not significantly different.

Conclusions In critically ill patients, weekly administration of 40 000 units of rHuEPO reduces allogeneic RBC transfusion and increases hemoglobin. Further study is needed to determine whether this reduction in RBC transfusion results in improved clinical outcomes.

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