Effect of Erythropoietin and Transfusion Threshold on Neurological Recovery After Traumatic Brain Injury

Abstract

There is limited information about the effect of erythropoietin or a high transfusion threshold in traumatic brain injury (TBI). To compare the effects of erythropoietin and two transfusion thresholds (7 and 10 g/dl) on neurological recovery after TBI. Randomized trial using a factorial design to test: i.) whether erythropoietin would fail to improve favorable outcomes by 20%, and ii.) whether a transfusion threshold of >10 g/dl would increase favorable outcomes without increasing complications. Neurosurgical intensive care units of two Houston level 1 trauma centers Between May 2006 and August 2012, 200 patients with closed head injury who were unable to follow commands were enrolled within 6 hours of injury; 102 patients received erythropoetin and 98 received placebo. Erythropoetin or placebo was initially dosed daily for 3 days and then weekly for 2 more weeks (n=74) and then the 24h and 48h doses were dropped for the remainder (n=126). Ninety-nine and 101 patients were assigned to the 7g/dl and 10g/dl transfusion thresholds. Intravenous erythropoietin 500 IU/kg or saline per dose. Transfusion threshold maintained with packed red blood cell transfusion. Glasgow Outcome Scale dichotomized as favorable (good recovery and moderate disability) and unfavorable (severe disability, vegetative, or dead) at 6 months post-injury. There was no erythropoeitin-transfusion threshold interaction. Compared to placebo (favorable outcome rate: 34/89 [38.2%]; 95%CI=28.2-49.1%), both erythropoetin groups were futile (first dosing regimen: 17/35 [48.6%]; 95%CI=31.4-66.0%, p=0.13, and second dosing regimen: 17/57 [29.8%]; 95%CI=18.4-43.4%, p 10 g/dl resulted in improved neurological outcome at 6 months and the 10 g/dl threshold was associated with a higher incidence of adverse events.. These findings do not support either approach in this setting.