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

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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.

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Acknowledgements

FAZ’s research program is supported by the University of Manitoba VPRI Research Investment Fund (RIF), University of Manitoba Rudy Falk Clinician-Scientist Professorship, the University of Manitoba Centre on Aging Fellowship, the Health Sciences Centre Foundation (HSCF) Winnipeg, the Manitoba Public Insurance (MPI) Neuroscience/TBI Research Endowment, the National Institutes of Health (NIH), and the Canadian Institutes of Health Research (CIHR). LF is supported through the University of Manitoba—Department of Surgery GFT Research Grant, and the University of Manitoba Office of Research Services (ORS)—University Research Grant Program (URGP). CB is supported through the University of Manitoba—Centre on Aging Fellowship. AG is supported through the University of Manitoba Clinician Investigator Program.

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Authors and Affiliations

  1. Biomedical Engineering, Faculty of Engineering, University of Manitoba, Winnipeg, Canada

    Logan Froese & Frederick A. Zeiler

  2. Department of Human Anatomy and Cell Science, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, Canada

    Carleen Batson, Alwyn Gomez & Frederick A. Zeiler

  3. Department of Surgery, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, Canada

    Alwyn Gomez, Josh Dian & Frederick A. Zeiler

  4. Centre on Aging, University of Manitoba, Winnipeg, Canada

    Frederick A. Zeiler

  5. Division of Anaesthesia, Addenbrooke’s Hospital, University of Cambridge, Cambridge, UK

    Frederick A. Zeiler

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LF was responsible for design, review of articles and manuscript composition. CB, JD and AG were responsible for review/synthesis of information and manuscript composition. FAZ was responsible for concept, design, data synthesis, manuscript composition and supervision.

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Correspondence to Frederick A. Zeiler.

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LF is supported by the Department of Surgery GFT Grant and the URGP at the University of Manitoba. CB is supported by the Centre on Aging Fellowship at the University of Manitoba. AG is supported by the Clinician Investigator Program, at the University of Manitoba. FAZ receives research support from the Manitoba Public Insurance (MPI) Neuroscience/TBI Research Endowment, the Health Sciences Centre Foundation Winnipeg, the United States National Institutes of Health (NIH) through the National Institute of Neurological Disorders and Stroke (NINDS), the Canadian Institutes of Health Research (CIHR), the Canadian Foundation for Innovation (CFI), the University of Manitoba VPRI Research Investment Fund (RIF), the University of Manitoba Centre on Aging, and the University of Manitoba Rudy Falk Clinician-Scientist Professorship.

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Froese, L., Batson, C., Gomez, A. et al. The Limited Impact of Current Therapeutic Interventions on Cerebrovascular Reactivity in Traumatic Brain Injury: A Narrative Overview. Neurocrit Care 34, 325–335 (2021). https://doi.org/10.1007/s12028-020-01003-4

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