Importance There is limited information about the effect of erythropoietin or a high transfusion threshold in traumatic brain injury (TBI). Objective To compare the effects of erythropoietin and two transfusion thresholds (7 and 10 g/dl) on neurological recovery after TBI. Design 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. Setting Neurosurgical intensive care units of two Houston level 1 trauma centers Participants 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. Intervention Intravenous erythropoietin 500 IU/kg or saline per dose. Transfusion threshold maintained with packed red blood cell transfusion. Main Outcome Glasgow Outcome Scale dichotomized as favorable (good recovery and moderate disability) and unfavorable (severe disability, vegetative, or dead) at 6 months post-injury. Results 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<0.001). Favorable outcome rates were 37/87 (42.5%) and 31/94 (33.0%) in the 7 and 10 g/dl threshold groups (95%CI for the difference = − 0.05 to 0.25, p=0.28). There was a higher incidence of thromboembolic events in the 10 g/dl threshold group (22/101 [21.8%] vs. 8/99 [8.1%], p=0.009). Conclusions and Relevance In patients with closed head injury, neither the administration of erythropoietin nor maintaining hemoglobin concentration > 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.

Infants appear sensitive to pharmacological reinforcing properties of low and relatively high ethanol doses. This sensitivity was revealed indirectly, by pairing gustatory stimuli with ethanol intoxication and then allowing these stimuli to act as second-order reinforcement for a quite different (tactile) stimulus. Behavioral activation elicited by the gustatory stimuli previously paired with a state of intoxication seems to compete with the expression of ethanol's motivational properties as assessed through intake tests.

Early experiences with alcohol comprising interactions with an alcohol-intoxicated dam result in motor impairment and enhanced ethanol intake later in life.