Abstract Details

Effect of Propranolol and Clonidine On Mechanically Ventilated Patients with Severe Traumatic Brain Injury: The DASH After TBI Randomized Control Trial
Neuro Trauma, Critical Care, and Sports Neurology
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Severe TBI is associated with sympathetic hyperactivity and higher days of mechanical ventilation.
This is a Phase II double-blinded, randomized, placebo-controlled, single-center pilot trial (NCT01322048). For power to detect a difference of 2 ventilator-free days, we planned to enroll 100 trauma patients with intracranial hemorrhage on head CT, ages 16-64 years, and GCS score≤8 within 24h of admission. At 50% accrual, the two-stage stopping rules were based on efficacy with Type I error=3%, and futility with conditional power<50%. Within 24h of enrollment, weighted adaptive minimization randomization assigned patients to placebo or treatment arms based on age and Marshall head CT classification by study neuroradiologists. The treatment arm received both propranolol and clonidine for 7 days. Propranolol was dosed 1mg IV q6h and clonidine was dosed 0.1mg PO(enterally) q12h. The placebo arm received paired IV and enteral placebos.
The study was stopped for futility at interim analysis after enrollment of 47 patients. The median ventilator-free days were not higher with treatment (median ventilator-free days 17.2 [0-19.8] with adrenergic blockade[n=21], 15.7 [0-19.3] with placebo[n=26], P=0.64 by Wilcoxon rank-sum test). Mortality was not affected by treatment (24% adrenergic blockade, 31% placebo, OR 0.71 [95% CI:0.15-3.07], P=0.74). While on treatment, no patient experienced a cardiac complication (dysrhythmia, myocardial infarction, or cardiac arrest). During the intervention period, blinding was not broken and non-study β-blockers or α2-agonists were not used.
Adrenergic blockade with propranolol and clonidine did not improve ventilator-free days after severe TBI. These findings require confirmation in larger studies to inform the use of β-blockers and α2-agonists in altering outcomes after TBI.
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