The Limited Impact of Current Therapeutic Interventions on Cerebrovascular Reactivity in Traumatic Brain Injury: A Narrative Overview

Abstract

Current intensive care unit (ICU) treatment strategies for traumatic brain injury (TBI) care focus on intracranial pressure (ICP)- and cerebral perfusion pressure (CPP)-directed therapeutics, dictated by guidelines. Impaired cerebrovascular reactivity in moderate/severe TBI is emerging as a major associate with poor outcome and appears to dominate the landscape of physiologic derangement over the course of a patient's ICU stay. Within this article, we review the literature on the known drivers of impaired cerebrovascular reactivity in adult TBI, highlight the current knowledge surrounding the impact of guideline treatment strategies on continuously monitored cerebrovascular reactivity, and discuss current treatment paradigms for impaired reactivity. Finally, we touch on the areas of future research, as we strive to develop specific therapeutics for impaired cerebrovascular reactivity in TBI. There exists limited literature to suggest advanced age, intracranial injury patterns of diffuse injury, and sustained ICP elevations may drive impaired cerebrovascular reactivity. To date, the literature suggests there is a limited impact of such ICP/CPP guideline-based therapies on cerebrovascular reactivity, with large portions of a given patients ICU period spent with impaired cerebrovascular reactivity. Emerging treatment paradigms focus on the targeting individualized CPP and ICP thresholds based on cerebrovascular reactivity, without directly targeting the pathways involved in its dysfunction. Further work involved in uncovering the molecular pathways involved in impaired cerebrovascular reactivity is required, so that we can develop therapeutics directed at its prevention and treatment.

Keywords: Autoregulation; Cerebrovascular reactivity; TBI; Therapeutics.