Intravenous norepinephrine (NE) is utilized commonly in critical care for cardiovascular support. NE’s impact on cerebrovasculature is unclear and may carry important implications during states of critical neurological illness. The aim of the study was to perform a scoping review of the literature on the cerebrovascular/cerebral blood flow (CBF) effects of NE. A search of MEDLINE, BIOSIS, EMBASE, Global Health, SCOPUS, and Cochrane Library from inception to December 2019 was performed. All manuscripts pertaining to the administration of NE, in which the impact on CBF/cerebral vasculature was recorded, were included. We identified 62 animal studies and 26 human studies. Overall, there was a trend to a direct vasoconstriction effect of NE on the cerebral vasculature, with conflicting studies having demonstrated both increases and decreases in regional CBF (rCBF) or global CBF. Healthy animals and those undergoing cardiopulmonary resuscitation demonstrated a dose‐dependent increase in CBF with NE administration. However, animal models and human patients with acquired brain injury had varied responses in CBF to NE administration. The animal models indicate an increase in cerebral vasoconstriction with NE administration through the alpha receptors in vessels. Global and rCBF during the injection of NE displays a wide variation depending on treatment and model/patient.

The impact of vasopressor and sedative drugs on cerebrovascular reactivity in traumatic brain injury (TBI) remains unclear. The aim of this study was to evaluate the impact of changes of doses of commonly administered sedation (i.e., propofol, fentanyl, and ketamine) and vasopressor agents (i.e., norepinephrine [NE], phenylephrine [PE], and vasopressin[VSP]) on cerebrovascular reactivity and compensatory reserve in patients with moderate/severe TBI. Using the Winnipeg Acute TBI Database, we identified 38 patients with more than 1000 distinct changes of infusion rates and more than 500 h of paired drug infusion/physiology data. Cerebrovascular reactivity was assessed using pressure reactivity index (PRx) and cerebral compensatory reserve was assessed using RAP (the correlation [R] between pulse amplitude of intracranial pressure [ICP; A] and ICP [P]). We evaluated the data in two phases. First, we assessed the relationship between mean hourly dose of medication and its relation to both mean hourly index values, and time spent above a given index threshold. Second, we evaluated time-series data for each individual dose change per medication, assessing for a statistically significant change in PRx and RAP metrics. The results of the analysis confirmed that, overall, the mean hourly dose of sedative (propofol, fentanyl, and ketamine) and vasopressor (NE, PE, and VSP) agents does not impact hourly cerebrovascular reactivity or compensatory reserve measures. Similarly, incremental dose changes in these medications in general do not lead to significant changes in cerebrovascular reactivity or compensatory reserve. For propofol with incremental dose increases, in situations where PRx is intact (i.e., PRx <0 prior), a statistically significant increase in PRx was seen. However, this may not indicate deteriorating cerebrovascular reactivity as the final PRx (∼0.05) may still be considered to be intact cerebrovascular reactivity. As such, this finding with regards to propofol remains “weak.” This study indicates that commonly administered sedative and vasopressor agents with incremental dosing changes have no clinically significant influence on cerebrovascular reactivity or compensatory reserve in TBI. These results should be considered preliminary, requiring further investigation.

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 P CO 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.