Cerebrovascular Response to Propofol, Fentanyl, and Midazolam in Moderate/Severe Traumatic Brain Injury: A Scoping Systematic Review of the Human and Animal Literature

Abstract

Intravenous propofol, fentanyl, and midazolam are utilized commonly in critical care for metabolic suppression and anesthesia. The impact of propofol, fentanyl, and midazolam on cerebrovasculature and cerebral blood flow (CBF) is unclear in traumatic brain injury (TBI) and may carry important implications, as care is shifting to focus on cerebrovascular reactivity monitoring/directed therapies. The aim of this study was to perform a scoping review of the literature on the cerebrovascular/CBF effects of propofol, fentanyl, and midazolam in human patients with moderate/severe TBI and animal models with TBI. A search of MEDLINE, BIOSIS, EMBASE, Global Health, SCOPUS, and the Cochrane Library from inception to May 2020 was performed. All articles were included pertaining to the administration of propofol, fentanyl, and midazolam, in which the impact on CBF/cerebral vasculature was recorded. We identified 14 studies: 8 that evaluated propofol, 5 that evaluated fentanyl, and 2 that evaluated midazolam. All studies suffered from significant limitations, including: small sample size, and heterogeneous design and measurement techniques. In general, there was no significant change seen in CBF/cerebrovascular response to administration of propofol, fentanyl, or midazolam during experiments where PCO 2 and mean arterial pressure (MAP) were controlled. This review highlights the current knowledge gap surrounding the impact of commonly utilized sedative drugs in TBI care. This work supports the need for dedicated studies, both experimental and human-based, evaluating the impact of these drugs on CBF and cerebrovascular reactivity/response in TBI.

Transcranial Doppler Based Cerebrovascular Reactivity Indices in Adult Traumatic Brain Injury: A Scoping Review of Associations With Patient Oriented Outcomes

“…The data was reported in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR; Tricco et al, 2018 ). The search strategy and methodology used here is similar to other systematically conducted scoping reviews published by our group ( Froese et al, 2020a , Froese et al,2020b , Froese et al,2020c ; Hasen et al, 2020 ).…”

Association Between Processed Electroencephalogram-Based Objectively Measured Depth of Sedation and Cerebrovascular Response: A Systematic Scoping Overview of the Human and Animal Literature

“…Appendix A of the Supplementary Materials provides the PRISMA checklist. Search strategy and methodology is similar to other scoping reviews published by our group (3,21,22).…”

“…The near ubiquitous use of sedation throughout a variety of critical care illnesses and its ability to help mediate the cascading secondary injury pathways in the setting of acute neurological injuries (1), highlights sedation as an important aspect of patient care in the intensive care unit (ICU). Despite the widespread use of sedation, the correlation between objectively measured depth of sedation, neurovascular coupling and cerebrovascular response/cerebral blood flow (CBF) is limited (2)(3)(4)(5). To date, most assessments of sedation depth in the ICU occur using bedside clinical examination scoring systems, which are confounded by inter-and intra-assessor heterogeneity (6)(7)(8).…”

“…Such is the case in the treatment of moderate/severe traumatic brain injuries (TBI), where sedation is used for its ability to reduce cerebral metabolic activity and conserve CBF with the hopes that it will maintain healthy homeostasis and reduce secondary injury (13,14). However, recent comprehensive reviews evaluating the impact of various commonly utilized sedative agents in TBI care, and their corresponding impact on CBF/cerebrovascular response, have demonstrated conflicting results (3,4,15). Studies identified in these reviews failed to record objectively measured sedation depth, and only commented on the sedative agent type and dosing.…”

Mismatch between Tissue Partial Oxygen Pressure and Near-Infrared Spectroscopy Neuromonitoring of Tissue Respiration in Acute Brain Trauma: The Rationale for Implementing a Multimodal Monitoring Strategy

“…The drugs administered (e.g., Propofol, barbiturates, 0.9% saline), comorbidities (e.g., heart failure), and the type of injury (e.g., penetrated or non-penetrated brain trauma) can each affect the parameters read (e.g., CBF, PbtO 2 ) and the patient’s prognosis, to a greater or lesser extent [ 134 , 135 , 136 ]. Furthermore, the pathogenesis that impairs the tissue respiration can also affect other physiological mechanisms, such as reduced inflows of metabolites and clearance of catabolites due to reduced CBF.…”