Effect of Erythropoietin and Transfusion Threshold on Neurological Recovery After Traumatic Brain Injury: A Randomized Clinical Trial

• Published in: JAMA : the journal of the American Medical Association 2014-07, Vol.312 (1), p.36-47
• Main Authors: Robertson, Claudia S, Hannay, H. Julia, Yamal, José-Miguel, Gopinath, Shankar, Goodman, J. Clay, Tilley, Barbara C, Baldwin, Athena, Rivera Lara, Lucia, Saucedo-Crespo, Hector, Ahmed, Osama, Sadasivan, Santhosh, Ponce, Luciano, Cruz-Navarro, Jovanny, Shahin, Hazem, Aisiku, Imoigele P, Doshi, Pratik, Valadka, Alex, Neipert, Leslie, Waguspack, Jace M, Rubin, M. Laura, Benoit, Julia S, Swank, Paul
• Format: Article
• Language: English
• Subjects: Adult; Adult and adolescent clinical studies; Anemia - complications; Anemia - etiology; Anemia - therapy; Biological and medical sciences; Brain damage; Brain Injuries - complications; Brain Injuries - therapy; Clinical trials; Erythrocyte Transfusion - adverse effects; Erythrocyte Transfusion - methods; Erythropoietin - administration & dosage; Female; General aspects; Glasgow Outcome Scale; Hemoglobin; Hemoglobins - analysis; Humans; Injuries of the nervous system and the skull. Diseases due to physical agents; Male; Medical research; Medical sciences; Middle Aged; Neurologic Examination; Neurology; Organic mental disorders. Neuropsychology; Persistent Vegetative State; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Reference Values; Severity of Illness Index; Thromboembolism - chemically induced; Traumas. Diseases due to physical agents; Treatment Outcome; Young Adult
• ISSN: 0098-7484; 1538-3598
• DOI: 10.1001/jama.2014.6490

IMPORTANCE: There is limited information about the effect of erythropoietin or a high hemoglobin transfusion threshold after a traumatic brain injury. OBJECTIVE: To compare the effects of erythropoietin and 2 hemoglobin transfusion thresholds (7 and 10 g/dL) on neurological recovery after traumatic brain injury. DESIGN, SETTING, AND PARTICIPANTS: Randomized clinical trial of 200 patients (erythropoietin, n = 102; placebo, n = 98) with closed head injury who were unable to follow commands and were enrolled within 6 hours of injury at neurosurgical intensive care units in 2 US level I trauma centers between May 2006 and August 2012. The study used a factorial design to test whether erythropoietin would fail to improve favorable outcomes by 20% and whether a hemoglobin transfusion threshold of greater than 10 g/dL would increase favorable outcomes without increasing complications. Erythropoietin or placebo was initially dosed daily for 3 days and then weekly for 2 more weeks (n = 74) and then the 24- and 48-hour doses were stopped for the remainder of the patients (n = 126). There were 99 patients assigned to a hemoglobin transfusion threshold of 7 g/dL and 101 patients assigned to 10 g/dL. INTERVENTIONS: Intravenous erythropoietin (500 IU/kg per dose) or saline. Transfusion threshold maintained with packed red blood cells. MAIN OUTCOMES AND MEASURES: Glasgow Outcome Scale score dichotomized as favorable (good recovery and moderate disability) or unfavorable (severe disability, vegetative, or dead) at 6 months postinjury. RESULTS: There was no interaction between erythropoietin and hemoglobin transfusion threshold. Compared with placebo (favorable outcome rate: 34/89 [38.2%; 95% CI, 28.1% to 49.1%]), both erythropoietin groups were futile (first dosing regimen: 17/35 [48.6%; 95% CI, 31.4% to 66.0%], P = .13; second dosing regimen: 17/57 [29.8%; 95% CI, 18.4% to 43.4%], P