Traumatic brain injury is a leading cause of death and disability worldwide. Interventions that mitigate secondary brain injury have the potential to improve outcomes for patients and reduce the impact on communities and society. Increased circulating catecholamines are associated with worse outcomes and there is supportive animal data and indications in human studies of benefit from beta-blockade after severe traumatic brain injury. Here we present the protocol for a dose-finding study using esmolol in adults commenced within 24 hours of severe traumatic brain injury. Esmolol has practical advantages and theoretical benefits as a neuroprotective agent in this setting, but these must be balanced against the known risk of secondary injury from hypotension. The aim of this study is to determine a dose schedule for esmolol, using the continual reassessment method, that combines a clinically significant reduction in heart rate as a surrogate for catecholamine drive with maintenance of cerebral perfusion pressure. The maximum tolerated dosing schedule for esmolol can then be tested for patient benefit in subsequent randomised controlled trials.

The authors have declared no competing interest.

ISRCTN 11038397

The study is funded by the Research for Patient Benefit (RfPB) programme of the National Institute for Health and Care Research (NIHR Award PB-PG-0418-20029). The views expressed in this article are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care.

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South Central Hampshire A Research Ethics Committee gave ethical approval for this work on behalf of the Research Ethics Service of the Health Research Authority (reference 20/SC/0219).

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