title: Effect of erythropoietin and transfusion threshold on neurological recovery after traumatic brain injury: a randomized clinical trial.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  METHODS
  Intravenous erythropoietin (500 IU/kg per dose) or saline. Transfusion threshold maintained with packed red blood cells.
  
  
  METHODS
  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 < .001). Favorable outcome rates were 37/87 (42.5%) for the hemoglobin transfusion threshold of 7 g/dL and 31/94 (33.0%) for 10 g/dL (95% CI for the difference, -0.06 to 0.25, P = .28). There was a higher incidence of thromboembolic events for the transfusion threshold of 10 g/dL (22/101 [21.8%] vs 8/99 [8.1%] for the threshold of 7 g/dL, odds ratio, 0.32 [95% CI, 0.12 to 0.79], P = .009).
  
  
  CONCLUSIONS
  In patients with closed head injury, neither the administration of erythropoietin nor maintaining hemoglobin concentration of greater than 10 g/dL resulted in improved neurological outcome at 6 months. The transfusion threshold of 10 g/dL was associated with a higher incidence of adverse events. These findings do not support either approach in this setting.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT00313716.
authors: Department of Neurosurgery, Baylor College of Medicine, Houston, Texas.
authors: Claudia S
authors: CS
authors: Robertson
authors: Department of Psychology, University of Houston, Houston, Texas.
authors: H Julia
authors: HJ
authors: Hannay
authors: Division of Biostatistics, University of Texas Health Science Center at Houston School of Public Health, Houston.
authors: José-Miguel
authors: JM
authors: Yamal
authors: Department of Neurosurgery, Baylor College of Medicine, Houston, Texas.
authors: Shankar
authors: S
authors: Gopinath
authors: Department of Pathology and Immunology, Baylor College of Medicine, Houston, Texas.
authors: J Clay
authors: JC
authors: Goodman
authors: Division of Biostatistics, University of Texas Health Science Center at Houston School of Public Health, Houston.
authors: Barbara C
authors: BC
authors: Tilley
authors: Department of Neurosurgery, Baylor College of Medicine, Houston, Texas.
authors: Athena
authors: A
authors: Baldwin
authors: Department of Neurosurgery, Baylor College of Medicine, Houston, Texas.
authors: Lucia
authors: L
authors: Rivera Lara
authors: Department of Neurosurgery, Baylor College of Medicine, Houston, Texas.
authors: Hector
authors: H
authors: Saucedo-Crespo
authors: Department of Neurosurgery, Baylor College of Medicine, Houston, Texas.
authors: Osama
authors: O
authors: Ahmed
authors: Department of Neurosurgery, Baylor College of Medicine, Houston, Texas.
authors: Santhosh
authors: S
authors: Sadasivan
authors: Department of Neurosurgery, Baylor College of Medicine, Houston, Texas.
authors: Luciano
authors: L
authors: Ponce
authors: Department of Neurosurgery, Baylor College of Medicine, Houston, Texas.
authors: Jovanny
authors: J
authors: Cruz-Navarro
authors: Department of Neurosurgery, Baylor College of Medicine, Houston, Texas.
authors: Hazem
authors: H
authors: Shahin
authors: University of Texas Health Sciences Center, Houston.
authors: Imoigele P
authors: IP
authors: Aisiku
authors: University of Texas Health Sciences Center, Houston.
authors: Pratik
authors: P
authors: Doshi
authors: University of Texas Health Sciences Center, Houston.
authors: Alex
authors: A
authors: Valadka
authors: Department of Psychology, University of Houston, Houston, Texas.
authors: Leslie
authors: L
authors: Neipert
authors: Department of Psychology, University of Houston, Houston, Texas.
authors: Jace M
authors: JM
authors: Waguspack
authors: Division of Biostatistics, University of Texas Health Science Center at Houston School of Public Health, Houston.
authors: M Laura
authors: ML
authors: Rubin
authors: Division of Biostatistics, University of Texas Health Science Center at Houston School of Public Health, Houston.
authors: Julia S
authors: JS
authors: Benoit
authors: Division of Biostatistics, University of Texas Health Science Center at Houston School of Public Health, Houston.
authors: Paul
authors: P
authors: Swank
mesh_terms: D000328:Adult; D000740:Anemia / Q000150:complications / Q000209:etiology / Q000628:therapy*; D001930:Brain Injuries / Q000150:complications* / Q000628:therapy; D017707:Erythrocyte Transfusion / Q000009:adverse effects* / Q000379:methods; D004921:Erythropoietin / Q000008:administration & dosage*; D005260:Female; D023261:Glasgow Outcome Scale; D006454:Hemoglobins / Q000032:analysis*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009460:Neurologic Examination; D018458:Persistent Vegetative State; D012016:Reference Values; D012720:Severity of Illness Index; D013923:Thromboembolism / Q000139:chemically induced; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D006454:Hemoglobins; D004921:Erythropoietin