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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 PCO₂ 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.

SUBMITTER: Froese L

PROVIDER: S-EPMC7685293 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:To evaluate the clinical effectiveness of bolus-dose fentanyl and midazolam to treat episodic intracranial hypertension in children with severe traumatic brain injury.Retrospective cohort.PICU in a university-affiliated children's hospital level I trauma center.Thirty-one children 0-18 years of age with severe traumatic brain injury (Glasgow Coma Scale score of ? 8) who received bolus doses of fentanyl and/or midazolam for treatment of episodic intracranial hypertension.None.The area under the curve from high-resolution intracranial pressure-time plots was calculated to represent cumulative intracranial hypertension exposure: area under the curve for intracranial pressure above 20 mm Hg (area under the curve-intracranial hypertension) was calculated in 15-minute epochs before and after administration of fentanyl and/or midazolam for the treatment of episodic intracranial hypertension. Our primary outcome measure, the difference between predrug and postdrug administration epochs (?area under the curve-intracranial hypertension), was calculated for all occurrences. We examined potential covariates including age, injury severity, mechanism, and time after injury; time after injury correlated with ?area under the curve-intracranial hypertension. In a mixed-effects model, with patient as a random effect, drug/dose combination as a fixed effect, and time after injury as a covariate, intracranial hypertension increased after administration of fentanyl and/or midazolam (overall aggregate mean ?area under the curve-intracranial hypertension = +17 mm Hg × min, 95% CI, 0-34 mm Hg × min; p = 0.04). The mean ?area under the curve-intracranial hypertension increased significantly after administration of high-dose fentanyl (p = 0.02), low-dose midazolam (p = 0.006), and high-dose fentanyl plus low-dose midazolam (0.007). Secondary analysis using age-dependent thresholds showed no significant impact on cerebral perfusion pressure deficit (mean ?area under the curve-cerebral perfusion pressure).Bolus dosing of fentanyl and midazolam fails to reduce the intracranial hypertension burden when administered for episodic intracranial hypertension. Paradoxically, we observed an overall increase in intracranial hypertension burden following drug administration, even after accounting for within-subject effects and time after injury. Future work is needed to confirm these findings in a prospective study design.

Project description:Age and biological sex are two potential important modifiers of cerebrovascular reactivity post-traumatic brain injury (TBI) requiring close evaluation for potential subgroup responses. The goal of this study was to provide a preliminary exploratory analysis of the impact of age and biological sex on measures of cerebrovascular function in moderate/severe TBI. Forty-nine patients from the prospectively maintained TBI database at the University of Manitoba with archived high-frequency digital cerebral physiology were evaluated. Cerebrovascular reactivity indices were derived as follows: PRx (correlation between intracranial pressure [ICP] and mean arterial pressure [MAP]), PAx (correlation between pulse amplitude of ICP [AMP] and MAP), and RAC (correlation between AMP and cerebral perfusion pressure [CPP]). Time above clinically significant thresholds for each index was calculated over different periods of the acute intensive care unit stay. The association between PRx, PAx, and RAC measures with age was assessed using linear regression, and an age trichotomization scheme (<40, 40-60, >60) using Kruskal-Wallis testing. Similarly, association with biological sex was tested using Mann-Whitney U testing. Biological sex did not demonstrate an impact on any measures of cerebrovascular reactivity. Linear regression between age and PAx and RAC demonstrated a statistically significant positive linear relationship. Median PAx and RAC measures between trichotomized age categories demonstrated statistically significant increases with advancing age. The PRx failed to demonstrate any statistically significant relationship with age in this cohort, suggesting that in elderly patients with controlled ICP, PAx and RAC may be better metrics for detecting impaired cerebrovascular reactivity. Biological sex appears to not be associated with differences in cerebrovascular reactivity in this cohort. The PRx performed the worst in detecting impaired cerebrovascular reactivity in those with advanced age, where PAx and RAC appear to have excelled. Future work is required to validate these findings and explore the utility of different cerebrovascular reactivity indices.

Project description:BackgroundLong-term physical, cognitive, and psychosocial problems resulting from moderate to severe traumatic brain injury (TBI) can prevent individuals from returning to preinjury lifestyles because of significant challenges with employment, leisure, and relationships. While physical activity (PA) is proposed as a cost-effective method to alleviate problems after moderate to severe TBI, there is no review to date that synthesizes the evidence for PA in the community-based context. Further, although sex- and gender-based considerations in research are considered requisite to good science, there is no review on PA and TBI that has included this explicit focus.ObjectiveThe purpose of this review is to map and synthesize the current evidence identified through a systematic search of community-based PA interventions for individuals of all ages with moderate to severe TBI and provide an overview of that evidence by asking the following research questions: (1) what are the characteristics of community-based PA programs for individuals with moderate to severe TBI, (2) what are the reported health-related outcomes and measurement tools used to evaluate them, and (3) what considerations have been given to sex and/or gender?MethodsSearches will be conducted of six academic databases for peer-reviewed articles. Two reviewers will independently screen the articles for inclusion and extract data for the analysis. The extracted data will be coded according to the Consensus on Exercise Reporting Template checklist and the Template for Intervention Description and Replication checklist to provide sufficient detail for replication.ResultsThe abstract screening was completed by two reviewers and the extracted data were analyzed. A qualitative synthesis and description of community-based PA interventions for individuals with moderate to severe TBI will be provided.ConclusionsThis scoping review will generate new knowledge from published and publicly available literature. Dissemination of the results will include activities related to knowledge transfer for community-based PA after moderate to severe TBI for future research and practice. Evidence-based recommendations, future directions, potential limitations, use of online/digital components, and the possible need for a systematic review will be discussed as well.International registered report identifier (irrid)DERR1-10.2196/24689.

Project description:BackgroundThe initiation, anatomic pattern, and extent of tau spread in traumatic brain injury (TBI), and the mechanism by which TBI leads to long-term tau pathology, remain controversial. Some studies suggest that moderate to severe TBI is sufficient to promote tau pathology; however, others suggest that it is simply a consequence of aging. We therefore conducted a systematic narrative review of the literature addressing whether a single moderate to severe head injury leads to long-term development of tauopathy in both humans and animal models.MethodsStudies considered for inclusion in this review assessed a single moderate to severe TBI, assessed tau pathology at long-term timepoints post-injury, comprised experimental or observational studies, and were peer-reviewed and published in English. Databases searched included: PUBMED, NCBI-PMC, EMBASE, Web of Science, Academic Search Premiere, and APA Psychnet. Search results were uploaded to Covidence®, duplicates were removed, and articles underwent an abstract and full-text screening process. Data were then extracted and articles assessed for risk of bias.FindingsOf 4,150 studies screened, 26 were eligible for inclusion, of which 17 were human studies, 8 were preclinical animal studies, and 1 included both human and preclinical animal studies. Most studies had low to moderate risk of bias. Most human and animal studies (n = 12 and 9, respectively) suggested that a single moderate to severe TBI resulted in greater development of long-term tauopathy compared to no history of head injury. This conclusion should be interpreted with caution, however, due to several limitations: small sample sizes; inconsistencies in controlling for confounding factors that may have affected tau pathology (e.g., family history of dementia or neurological illnesses, apolipoprotein E genotype, etc.), inclusion of mostly males, and variation in reporting injury parameters.InterpretationResults indicate that a single moderate to severe TBI leads to greater chronic development of tauopathy compared to no history of head injury. This implies that tau pathology induced may not be transient, but can progressively develop over time in both humans and animal models. Targeting these tau changes for therapeutic intervention should be further explored to elucidate if disease progression can be reversed or mitigated.

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

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