Effect of erythropoietin and transfusion threshold on neurological recovery after traumatic brain injury: A randomized clinical trial

Claudia S. Robertson, H. Julia Hannay, José Miguel Yamal, Shankar Gopinath, J. Clay Goodman, Barbara C. Tilley, Athena Baldwin, Lucia Rivera Lara, Hector Saucedo-Crespo, Osama Ahmed, Santhosh Sadasivan, Luciano Ponce, Jovanny Cruz-Navarro, Hazem Shahin, Imoigele P. Aisiku, Pratik Doshi, Alex Valadka, Leslie Neipert, Jace M. Waguspack, M. Laura RubinJulia S. Benoit, Paul Swank

Research output: Contribution to journalArticle

Abstract

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 < .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 AND RELEVANCE: 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. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00313716

Original languageEnglish (US)
Pages (from-to)36-47
Number of pages12
JournalJAMA - Journal of the American Medical Association
Volume312
Issue number1
DOIs
StatePublished - Jan 1 2014
Externally publishedYes

ASJC Scopus subject areas

  • Medicine(all)

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    Robertson, C. S., Hannay, H. J., Yamal, J. M., Gopinath, S., Goodman, J. C., Tilley, B. C., Baldwin, A., Lara, L. R., Saucedo-Crespo, H., Ahmed, O., Sadasivan, S., Ponce, L., Cruz-Navarro, J., Shahin, H., Aisiku, I. P., Doshi, P., Valadka, A., Neipert, L., Waguspack, J. M., ... Swank, P. (2014). Effect of erythropoietin and transfusion threshold on neurological recovery after traumatic brain injury: A randomized clinical trial. JAMA - Journal of the American Medical Association, 312(1), 36-47. https://doi.org/10.1001/jama.2014.6490