Beta-adrenergic blockade for attenuation of catecholamine surge after traumatic brain injury: a randomized pilot trial

BACKGROUND: Beta-blockers have been proven in multiple studies to be beneficial in patients with traumatic brain injury. Few prospective studies have verified this and no randomized controlled trials. Additionally, most studies do not titrate the dose of beta-blockers to therapeutic effect. We hypothesize that propranolol titrated to effect will confer a survival benefit in patients with traumatic brain injury. METHODS: A randomized controlled pilot trial was performed during a 24-month period. Patients with traumatic brain injury were randomized to propranolol or control group for a 14-day study period. Variables collected included demographics, injury severity, physiologic parameters, urinary catecholamines, and outcomes. Patients receiving propranolol were compared with the control group. RESULTS: Over the study period, 525 patients were screened, 26 were randomized, and 25 were analyzed. Overall, the mean age was 51.3 years and the majority were male with blunt mechanism. The mean Injury Severity Score was 21.8 and median head Abbreviated Injury Scale score was 4. Overall mortality was 20.0%. Mean arterial pressure was higher in the treatment arm as compared with control (p=0.021), but no other differences were found between the groups in demographics, severity of injury, severity of illness, physiologic parameters, or mortality (7.7% vs. 33%; p=0.109). No difference was detected over time in any variables with respect to treatment, urinary catecholamines, or physiologic parameters. Glasgow Coma Scale (GCS), Sequential Organ Failure Assessment, and Acute Physiology and Chronic Health Evaluation scores all improved over time. GCS at study end was significantly higher in the treatment arm (11.7 vs. 8.9; p=0.044). Finally, no difference was detected with survival analysis over time between groups. CONCLUSIONS: Despite not being powered to show statistical differences between groups, GCS at study end was significantly improved in the treatment arm and mortality was improved although not at a traditional level of significance. The study protocol was safe and feasible to apply to an appropriately powered larger multicenter study. LEVEL OF EVIDENCE: Level 2—therapeutic.