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Clinical Trial
. 2023 Jun 9;27(1):228.
doi: 10.1186/s13054-023-04479-6.

Effect of propranolol and clonidine after severe traumatic brain injury: a pilot randomized clinical trial

Mina F Nordness  1   2 , Amelia W Maiga  1   2   3 , Laura D Wilson  4   5 , Tatsuki Koyama  1   6 , Erika L Rivera  1   2 , Shayan Rakhit  1   2 , Michael de Riesthal  4 , Cari L Motuzas  7 , Madison R Cook  1   8 , Deepak K Gupta  9 , James C Jackson  1 , Shawniqua Williams Roberson  1 , William J Meurer  10 , Roger J Lewis  11 , Geoffrey T Manley  12 , Pratik P Pandharipande  1   13   14   15 , Mayur B Patel  16   17   18   19   20   21   22
Affiliations
Clinical Trial

Effect of propranolol and clonidine after severe traumatic brain injury: a pilot randomized clinical trial

Mina F Nordness et al. Crit Care. .

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.

Keywords: Adrenergic blockade; Critical care; Paroxysmal sympathetic hyperactivity; Traumatic brain injury.

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Conflict of interest statement

Pfizer, Inc. (previously Hospira Inc.) has provided unrelated research support to PPP. Haemonetics, Inc. has provided unrelated research support to MBP. For the remaining authors, no competing interests were declared.

Figures

Fig. 1
Fig. 1
Screening, enrollment, and randomization for propranolol and clonidine versus double placebo after severe traumatic brain injury
Fig. 2
Fig. 2
Kaplan–Meier survival curves of propranolol and clonidine (treatment) versus double placebo after severe traumatic brain injury
See this image and copyright information in PMC

References

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