Effect of propranolol and clonidine after severe traumatic brain injury: a pilot randomized clinical trial
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Published:2023-06-09
Issue:1
Volume:27
Page:
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ISSN:1364-8535
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Container-title:Critical Care
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language:en
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Short-container-title:Crit Care
Author:
Nordness Mina F.,Maiga Amelia W.,Wilson Laura D.,Koyama Tatsuki,Rivera Erika L.,Rakhit Shayan,de Riesthal Michael,Motuzas Cari L.,Cook Madison R.,Gupta Deepak K.,Jackson James C.,Williams Roberson Shawniqua,Meurer William J.,Lewis Roger J.,Manley Geoffrey T.,Pandharipande Pratik P.,Patel Mayur B.
Abstract
Abstract
Objective
To evaluate the safety, feasibility, and efficacy of combined adrenergic blockade with propranolol and clonidine in patients with severe traumatic brain injury (TBI).
Background
Administration of adrenergic blockade after severe TBI is common. To date, no prospective trial has rigorously evaluated this common therapy for benefit.
Methods
This phase II, single-center, double-blinded, pilot randomized placebo-controlled trial included patients aged 16–64 years with severe TBI (intracranial hemorrhage and Glasgow Coma Scale score ≤ 8) within 24 h of ICU admission. Patients received propranolol and clonidine or double placebo for 7 days. The primary outcome was ventilator-free days (VFDs) at 28 days. Secondary outcomes included catecholamine levels, hospital length of stay, mortality, and long-term functional status. A planned futility assessment was performed mid-study.
Results
Dose compliance was 99%, blinding was intact, and no open-label agents were used. No treatment patient experienced dysrhythmia, myocardial infarction, or cardiac arrest. The study was stopped for futility after enrolling 47 patients (26 placebo, 21 treatment), per a priori stopping rules. There was no significant difference in VFDs between treatment and control groups [0.3 days, 95% CI (− 5.4, 5.8), p = 1.0]. Other than improvement of features related to sympathetic hyperactivity (mean difference in Clinical Features Scale (CFS) 1.7 points, CI (0.4, 2.9), p = 0.012), there were no between-group differences in the secondary outcomes.
Conclusion
Despite the safety and feasibility of adrenergic blockade with propranolol and clonidine after severe TBI, the intervention did not alter the VFD outcome. Given the widespread use of these agents in TBI care, a multi-center investigation is warranted to determine whether adrenergic blockade is of therapeutic benefit in patients with severe TBI.
Trial Registration Number NCT01322048.
Funder
National Institute on Aging
National Institute of General Medical Sciences
School of Medicine, Vanderbilt University
National Institute of Neurological Disorders and Stroke
National Heart, Lung, and Blood Institute
U.S. Department of Veterans Affairs
Eastern Association for the Surgery of Trauma
Vanderbilt Institute for Clinical and Translational Research
Publisher
Springer Science and Business Media LLC
Subject
Critical Care and Intensive Care Medicine
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