This Article  • Full text  • PDF  • Send to a friend  • Save in My Folder  • Save to citation manager  • Permissions  Citing Articles  • Citation map  • Citing articles on HighWire  • Citing articles on Web of Science (181)  • Contact me when this article is cited  Related Content  • Related letters  • Related article  • Similar articles in JAMA  Topic Collections  • Critical Care/ Intensive Care Medicine  • Critical Care Medicine, Other  • Randomized Controlled Trial  • Hematology/ Hematologic Malignancies  • Anemias  • Hematology, Other  • Alert me on articles by topic  Social Bookmarking   What's this?

A Randomized Controlled Trial

Howard L. Corwin, MD; Andrew Gettinger, MD; Ronald G. Pearl, MD, PhD; Mitchell P. Fink, MD; Mitchell M. Levy, MD; Marc J. Shapiro, MD; Michael J. Corwin, MD; Theodore Colton, ScD; for the EPO Critical Care Trials Group

JAMA. 2002;288:2827-2835.

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.

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.

CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter     What's this?

RELATED LETTERS

Erythropoietin and Transfusions Among Critically Ill Patients
Sean M. Bagshaw and William A. Ghali
JAMA. 2003;289(12):1511.
EXTRACT | FULL TEXT  

Erythropoietin and Transfusions Among Critically Ill Patients
Kevin C. Abbott
JAMA. 2003;289(12):1511-1512.
EXTRACT | FULL TEXT  

RELATED ARTICLE

Should Patients in Intensive Care Units Receive Erythropoietin?
Jeffrey L. Carson
JAMA. 2002;288(22):2884-2886.
EXTRACT | FULL TEXT  

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES

Lipopolysaccharide Evokes Resistance to Erythropoiesis Induced by the Long-Acting Erythropoietin Analogue Darbepoetin Alfa in Rats
Brendt et al.
Anesth. Analg. 2009;109:705-711.
ABSTRACT | FULL TEXT  

The Erythropoietin NeuroProtective Effect: Assessment in CABG Surgery (TENPEAKS): A Randomized, Double-Blind, Placebo Controlled, Proof-of-Concept Clinical Trial
Haljan et al.
Stroke 2009;40:2769-2775.
ABSTRACT | FULL TEXT  

Red blood cell transfusions in acute paediatrics
Morley
EDUCATION AND PRACTICE 2009;94:65-73.
ABSTRACT | FULL TEXT  

Optimizing Anemia Management in Hospitalized Patients with End-Stage Renal Disease
Heung et al.
The Annals of Pharmacotherapy 2009;43:276-282.
ABSTRACT | FULL TEXT  

Anemia and RBC Transfusion in the ICU
Thomas
ACCP Crit Care Med Brd Rev 2009;20:357-368.
FULL TEXT  

A Comparative Review of Erythropoiesis Stimulating Agents
Metzger et al.
Journal of Pharmacy Practice 2008;21:424-430.
ABSTRACT  

Anemia in the Critically Ill Patient
Hassan
Journal of Pharmacy Practice 2008;21:405-410.
ABSTRACT  

Clinical Year in Review IV: Acute Respiratory Distress Syndrome, Radiology in the Intensive Care Unit, Nonpulmonary Critical Care, and Pulmonary Infections in the Immunocompromised Host
Ware
Proc Am Thorac Soc 2008;5:755-760.
FULL TEXT  

Anemia of Inflammation in Critically Ill Patients
Sihler and Napolitano
J Intensive Care Med 2008;23:295-302.
ABSTRACT  

Anemia, Blood Loss, and Blood Transfusions in North American Children in the Intensive Care Unit
Bateman et al.
Am. J. Respir. Crit. Care Med. 2008;178:26-33.
ABSTRACT | FULL TEXT  

Erythropoietic agents for anemia of critical illness
Shermock et al.
Am J Health Syst Pharm 2008;65:540-546.
ABSTRACT | FULL TEXT  

Sepsis: A Clinical Update
Ventetuolo and Levy
CJASN 2008;3:571-577.
FULL TEXT  

Cost Analytic Model to Determine the Least Costly Inpatient Erythropoiesis Stimulating Therapy Regimen
Sikand et al.
The Annals of Pharmacotherapy 2008;42:16-23.
ABSTRACT | FULL TEXT  

Epoetin Alfa in Critically Ill Patients
Mikhail et al.
NEJM 2007;357:2515-2517.
FULL TEXT  

Erythropoietin-receptor agonists in critically ill patients: a meta-analysis of randomized controlled trials
Zarychanski et al.
CMAJ 2007;177:725-734.
ABSTRACT | FULL TEXT  

Erythropoietin use in critically ill patients: forest and trees
Corwin
CMAJ 2007;177:747-749.
FULL TEXT  

Efficacy and Safety of Epoetin Alfa in Critically Ill Patients
Corwin et al.
NEJM 2007;357:965-976.
ABSTRACT | FULL TEXT  

A Meta-analysis of Randomized Controlled Trials in Critically Ill Patients to Evaluate the Dose-Response Effect of Erythropoietin
Turaga et al.
J Intensive Care Med 2007;22:270-282.
ABSTRACT  

Questionable conclusions about epoetin alfa
Kruse and Lee
Am J Health Syst Pharm 2007;64:1789-1791.
FULL TEXT  

Effect of preprinted order form on epoetin alfa prescribing
Garrelts et al.
Am J Health Syst Pharm 2007;64:1732-1738.
ABSTRACT | FULL TEXT  

Blood conservation in the critically ill
Thomas and Martinez
Am J Health Syst Pharm 2007;64:S11-S18.
ABSTRACT | FULL TEXT  

Erythropoietic therapy: Cost efficiency and reimbursement
Jaspan
Am J Health Syst Pharm 2007;64:S19-S29.
ABSTRACT | FULL TEXT  

Nononcologic Use of Human Recombinant Erythropoietin Therapy in Hospitalized Patients
Fischer et al.
Arch Intern Med 2007;167:840-846.
ABSTRACT | FULL TEXT  

Anemia in cancer and critical care patients: Pharmacoeconomic considerations
Reeder
Am J Health Syst Pharm 2007;64:S22-S27.
ABSTRACT | FULL TEXT  

Consultative hematology
McCrae et al.
ASH-SAP 2007;2007:466-505.
FULL TEXT  

Anaemia during critical illness
Walsh and Saleh
Br J Anaesth 2006;97:278-291.
FULL TEXT  

Erythropoiesis Abnormalities Contribute to Early-Onset Anemia in Patients with Septic Shock
Claessens et al.
Am. J. Respir. Crit. Care Med. 2006;174:51-57.
ABSTRACT | FULL TEXT  

Intensive care and emergency medicine: progress over the past 25 years.
Vincent et al.
Chest 2006;129:1061-1067.
ABSTRACT | FULL TEXT  

Cost Analysis of Erythropoietic-Stimulating Therapy Dosing in Oncology Inpatients
Killian et al.
The Annals of Pharmacotherapy 2006;40:421-426.
ABSTRACT | FULL TEXT  

Erythropoietin in the critically ill: what is the evidence?
Corwin and Eckardt
Nephrol Dial Transplant 2005;20:2605-2608.
FULL TEXT  

Pathophysiology of Oxygen Delivery in Respiratory Failure
Levy
Chest 2005;128:547S-553S.
ABSTRACT | FULL TEXT  

Anemia in the Long-term Ventilator-Dependent Patient With Respiratory Failure
Silver
Chest 2005;128:568S-575S.
ABSTRACT | FULL TEXT  

The Impact of Anemia in Patients With Respiratory Failure
Ouellette
Chest 2005;128:576S-582S.
ABSTRACT | FULL TEXT  

Recombinant Human Erythropoietin Use in a Critically Ill Jehovah's Witness After Cardiac Surgery
Price et al.
Anesth. Analg. 2005;101:325-327.
ABSTRACT | FULL TEXT  

Inflammatory cytokine inhibition of erythropoiesis in patients implanted with a mechanical circulatory assist device
Pierce and Larson
Perfusion 2005;20:83-90.
ABSTRACT  

Transfusion Practice in the ICU: When Will We Apply the Evidence?
Shorr and Jackson
Chest 2005;127:702-705.
FULL TEXT  

Epoetin alfa protocol and multidisciplinary blood-conservation program for critically ill patients
Pell et al.
Am J Health Syst Pharm 2005;62:400-405.
ABSTRACT | FULL TEXT  

Anemia, Allogenic Blood Transfusion, and Immunomodulation in the Critically Ill
Raghavan and Marik
Chest 2005;127:295-307.
ABSTRACT | FULL TEXT  

Medical management of patients with multiple organ dysfunction arising from acute radiation syndrome
Jackson et al.
Br. J. Radiol. 2005;Supplement_27:161-168.
ABSTRACT | FULL TEXT  

Better Reporting of Harms in Randomized Trials: An Extension of the CONSORT Statement
Ioannidis et al.
ANN INTERN MED 2004;141:781-788.
ABSTRACT | FULL TEXT  

Prognostic Implication of Anemia on In-Hospital Outcomes After Percutaneous Coronary Intervention
McKechnie et al.
Circulation 2004;110:271-277.
ABSTRACT | FULL TEXT  

Transfusion-Related Acute Lung Injury: A Review
Looney et al.
Chest 2004;126:249-258.
ABSTRACT | FULL TEXT  

Comment: use of epoetin alfa in critically ill patients
Darveau and Notebaert
The Annals of Pharmacotherapy 2004;38:1325-1326.
FULL TEXT  

Use of Epoetin Alfa in Critically Ill Patients
Pajoumand et al.
The Annals of Pharmacotherapy 2004;38:641-648.
ABSTRACT | FULL TEXT  

Influence of Clinical and Economical Factors on the Expert Rating of Appropriateness of Preoperative Use of Recombinant Erythropoietin in Elective Orthopedic Surgery Patients
Taffe et al.
Med Decis Making 2004;24:122-130.
ABSTRACT  

Epoetin Alfa: Clinical Evolution of a Pleiotropic Cytokine
Henry et al.
Arch Intern Med 2004;164:262-276.
ABSTRACT | FULL TEXT  

Intensive care and invasive ventilation in the elderly patient, implications of chronic lung disease and comorbidities
Nielson and Wingete
Chronic Respiratory Disease 2004;1:43-54.
ABSTRACT  

The cardiovascular effects of erythropoietin
Smith et al.
Cardiovasc Res 2003;59:538-548.
ABSTRACT | FULL TEXT  

The Hematologic System as a Marker of Organ Dysfunction in Sepsis
Aird
Mayo Clin Proc. 2003;78:869-881.
ABSTRACT  

Erythropoietin and Transfusions Among Critically Ill Patients
Bagshaw and Ghali
JAMA 2003;289:1511-1511.
FULL TEXT  

Erythropoietin and Transfusions Among Critically Ill Patients--Reply
Corwin
JAMA 2003;289:1512-1512.
FULL TEXT  

Erythropoietin and Transfusions Among Critically Ill Patients
Abbott
JAMA 2003;289:1511-1512.
FULL TEXT  

Erythropoietin for Anemic Patients in the ICU?
JWatch Gastroenterology 2003;2003:8-8.
FULL TEXT  

Erythropoietin for Anemic Patients in the ICU?
JWatch General 2003;2003:3-3.
FULL TEXT  

Should Patients in Intensive Care Units Receive Erythropoietin?
Carson
JAMA 2002;288:2884-2886.
FULL TEXT