Cerebrovascular Response to Phenylephrine in Traumatic Brain Injury: A Scoping Systematic Review of the Human and Animal Literature.
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SUBMITTER: Froese L
PROVIDER: S-EPMC8240891 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description: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.
| S-EPMC7685293 | biostudies-literature
Project description: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.
| S-EPMC7510331 | biostudies-literature
Project description:Traumatic brain injury (TBI) results in dysfunction of the cerebrovasculature. Gap junctions coordinate vasomotor responses and evidence suggests that they are involved in cerebrovascular dysfunction after TBI. Gap junctions are comprised of connexin proteins (Cxs), of which Cx37, Cx40, Cx43, and Cx45 are expressed in vascular tissue. This study tests the hypothesis that TBI alters Cx mRNA and protein expression in cerebral vascular smooth muscle and endothelial cells. Anesthetized (1.5% isoflurane) male Sprague-Dawley rats received sham or fluid-percussion TBI. Two, 6, and 24?h after, cerebral arteries were harvested, fresh-frozen for RNA isolation, or homogenized for Western blot analysis. Cerebral vascular endothelial and smooth muscle cells were selected from frozen sections using laser capture microdissection. RNA was quantified by ribonuclease protection assay. The mRNA for all four Cx genes showed greater expression in the smooth muscle layer compared to the endothelial layer. Smooth muscle Cx43 mRNA expression was reduced 2 ?h and endothelial Cx45 mRNA expression was reduced 24? h after injury. Western blot analysis revealed that Cx40 protein expression increased, while Cx45 protein expression decreased 24 ?h after injury. These studies revealed significant changes in the mRNA and protein expression of specific vascular Cxs after TBI. This is the first demonstration of cell type-related differential expression of Cx mRNA in cerebral arteries, and is a first step in evaluating the effects of TBI on gap junction communication in the cerebrovasculature.
| S-EPMC3172862 | biostudies-literature
Project description:BACKGROUND:The American Congress of Rehabilitation Medicine (ACRM) in 2010 called for more head injury research on gender disparities to bridge the gender gap for the short-and long-term effects of TBI, including sexual and reproductive outcomes. In this paper, we review the state of the literature before and after the ACRM announcement, and evaluate how research teams have considered females and mildly injured TBI(mTBI)/concussion groups in post-TBI-related changes in sexual functioning. METHODS:The research question for this scoping review was "what is the state of the literature in the evaluation of post-TBI sexual changes for women, and individuals with mTBI?" Using the 2010 ACRM call for action as a line of demarcation, we compared our findings before and after the 2010 announcement. RESULTS:We identified 9 research studies that addressed sexual functioning changes in females and mTBI/concussion groups. Four of the nine were published before the 2010 ACRM announcement, and five were published after. The representation of female research participants increased steadily over the 28-year timespan. The proportion of individuals with mTBI included in the post-2010 era was higher than the earlier time period. Consistently, women with mTBI reported more adverse sexual outcomes compared to male cohorts, orthopaedic, and non-injured comparison groups. This observation persisted regardless of recruitment site (rehabilitation center/Emergency Department (ED)/Community) or time of outcome assessment (acute versus chronic). The findings also remained despite the heterogeneity of survey questionnaires used to evaluate sexual functioning outcomes. Excluding the most recent 2019 study, none of the research groups compared the findings by TBI severity, making it difficult to fully understand how concussion-related sexual changes compare to more severe forms of the head injury. The long term impacts of the sexual changes, such as infertility and relationship discord were also absent across all studies; even though most evaluated outcomes chronically (some as far out as 20?years post injury). CONCLUSION:The number of publications in the era before the ACRM call for action and afterwards were almost identical. In order to tailor interventions for the appropriate groups of TBI patients, more neurosexuality research is needed to increase awareness of the importance of sexuality as a health outcome for individuals with neurodisabilities.
| S-EPMC7050144 | biostudies-literature
Project description:BackgroundMild traumatic brain injury (mTBI) occurs at a higher frequency among military personnel than among civilians. A common symptom of mTBIs is cognitive dysfunction. Health care professionals use neuropsychological assessments as part of a multidisciplinary and best practice approach for mTBI management. Such assessments support clinical diagnosis, symptom management, rehabilitation, and return-to-duty planning. Military health care organizations currently use computerized neurocognitive assessment tools (NCATs). NCATs and more traditional neuropsychological assessments present unique challenges in both clinical and military settings. Many research gaps remain regarding psychometric properties, usability, acceptance, feasibility, effectiveness, sensitivity, and utility of both types of assessments in military environments.ObjectiveThe aims of this study were to explore evidence regarding the use of NCATs among military personnel who have sustained mTBIs; evaluate the psychometric properties of the most commonly tested NCATs for this population; and synthesize the data to explore the range and extent of NCATs among this population, clinical recommendations for use, and knowledge gaps requiring future research.MethodsStudies were identified using MEDLINE, Embase, American Psychological Association PsycINFO, CINAHL Plus with Full Text, Psych Article, Scopus, and Military & Government Collection. Data were analyzed using descriptive analysis, thematic analysis, and the Randolph Criteria. Narrative synthesis and the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-analyses extension for Scoping Reviews) guided the reporting of findings. The psychometric properties of NCATs were evaluated with specific criteria and summarized.ResultsOf the 104 papers, 33 met the inclusion criteria for this scoping review. Thematic analysis and NCAT psychometrics were reported and summarized.ConclusionsWhen considering the psychometric properties of the most commonly used NCATs in military populations, these assessments have yet to demonstrate adequate validity, reliability, sensitivity, and clinical utility among military personnel with mTBIs. Additional research is needed to further validate NCATs within military populations, especially for those living outside of the United States and individuals experiencing other conditions known to adversely affect cognitive processing. Knowledge gaps remain, warranting further study of psychometric properties and the utility of baseline and normative testing for NCATs.
| S-EPMC7939942 | biostudies-literature
Project description:Background: Current understanding of the impact that sedative agents have on neurovascular coupling, cerebral blood flow (CBF) and cerebrovascular response remains uncertain. One confounding factor regarding the impact of sedative agents is the depth of sedation, which is often determined at the bedside using clinical examination scoring systems. Such systems do not objectively account for sedation depth at the neurovascular level. As the depth of sedation can impact CBF and cerebral metabolism, the need for objective assessments of sedation depth is key. This is particularly the case in traumatic brain injury (TBI), where emerging literature suggests that cerebrovascular dysfunction dominates the burden of physiological dysfunction. Processed electroencephalogram (EEG) entropy measures are one possible solution to objectively quantify depth of sedation. Such measures are widely employed within anesthesia and are easy to employ at the bedside. However, the association between such EEG measures and cerebrovascular response remains unclear. Thus, to improve our understanding of the relationship between objectively measured depth of sedation and cerebrovascular response, we performed a scoping review of the literature. Methods: A systematically conduced scoping review of the existing literature on objectively measured sedation depth and CBF/cerebrovascular response was performed, search multiple databases from inception to November 2020. All available literature was reviewed to assess the association between objective sedation depth [as measured through processed electroencephalogram (EEG)] and CBF/cerebral autoregulation. Results: A total of 13 articles, 12 on adult humans and 1 on animal models, were identified. Initiation of sedation was found to decrease processed EEG entropy and CBF/cerebrovascular response measures. However, after this initial drop in values there is a wide range of responses in CBF seen. There were limited statistically reproduceable associations between processed EEG and CBF/cerebrovascular response. The literature body remains heterogeneous in both pathological states studied and sedative agent utilized, limiting the strength of conclusions that can be made. Conclusions: Conclusions about sedation depth, neurovascular coupling, CBF, and cerebrovascular response are limited. Much further work is required to outline the impact of sedation on neurovascular coupling.
| S-EPMC8415224 | biostudies-literature
Project description:Traumatic cerebrovascular injury (TCVI) is a common pathologic mechanism of traumatic brain injury (TBI) and presents an attractive target for intervention. The aims of this study were to assess cerebral blood flow (CBF) and cerebrovascular reactivity (CVR) using magnetic resonance imaging (MRI) to assess their value as biomarkers of TCVI in chronic TBI, characterize the spatial distribution of TCVI, and assess the relationships between each biomarker and neuropsychological and clinical assessments. Forty-two subjects (27 chronic TBI, 15 age- and gender-matched healthy volunteers) were studied cross-sectionally. CBF was measured by arterial spin labeling and CVR by assessing the MRI-blood oxygen level-dependent signal with hypercapnia challenge. A focused neuropsychological battery adapted from the TBI Common Data Elements and neurobehavioral symptom questionnaires were administered at the time of the imaging session. Chronic TBI subjects showed a significant reduction in mean global, gray matter (GM), and white matter (WM) CVR, compared with healthy volunteers (p < 0.001). Mean GM CVR had the greatest effect size (Cohen's d = 0.9). CVR maps in chronic TBI subjects showed patchy, multifocal CVR deficits. CBF discriminated poorly between TBI subjects and healthy volunteers and did not correlate with CVR. Mean global CVR correlated best with chronic neurobehavioral symptoms among TBI subjects. Global, GM, and WM CVR are reliable and potentially useful biomarkers of TCVI in the chronic stage after moderate-to-severe TBI. CBF is less useful as biomarker of TCVI. CVR correlates best with chronic TBI symptoms. CVR has potential as a predictive and pharmacodynamic biomarker for interventions targeting TCVI.
| S-EPMC6016094 | biostudies-literature
Project description:To date, there has been limited literature exploring the association between age and sex with cerebrovascular reactivity (CVR) in moderate/severe traumatic brain injury (TBI). Given the known link between age, sex, and cerebrovascular function, knowledge of the impacts on continuously assessed CVR is critical for the development of future therapeutics. We conducted a scoping review of the literature for studies that had a direct statistical interrogation of the relationship between age, sex, and continuous intracranial pressure (ICP)-based indices of CVR in moderate/severe TBI. The ICP-based indices researched included: pressure reactivity index (PRx), pulse amplitude index (PAx), and RAC. MEDLINE, BIOSIS, EMBASE, SCOPUS, Global Health, and the Cochrane library were searched from inception to June 2021 for relevant articles. A total of 10 original studies fulfilled our inclusion criteria. Nine of the articles documented a correlation between advanced age and worse CVR, with eight using PRx (2192 total patients), three using PAx (978 total patients), and one using RAC (358 total patients), p < 0.05; R ranging from 0.17 to 0.495 for all indices across all studies. Three articles (1256 total patients) displayed a correlation between biological sex and PRx, with females trending towards higher PRx values (p < 0.05) in the limited available literature. However, no literature exists comparing PAx or RAC with biological sex. Findings showed that aging was associated with impaired CVR. We observed a trend between female sex and worse PRx values, but the literature was limited and statistical significance was borderline. The identified studies were few in number, carried significant population heterogeneity, and utilized grand averaging of large epochs of physiology during statistical comparisons with age and biological sex. Because of the heterogeneous nature of TBI populations and limited focus on the effects of age and sex on outcomes in TBI, it is challenging to highlight the differences between the indices and patient age groups and sex. The largest study showing an association between PRx and age was done by Zeiler and colleagues, where 165 patients were studied noting that patients with a mean PRx value above zero had a mean age above 51.4 years versus a mean age of 41.4 years for those with a mean PRx value below zero (p = 0.0007). The largest study showing an association between PRx and sex was done by Czosnyka and colleagues, where 469 patients were studied noting that for patients <50 years of age, PRx was worse in females (0.11 ± 0.047) compared to males (0.044 ± 0.031), p < 0.05. The findings from these 10 studies provide preliminary data, but are insufficient to definitively characterize the impact of age and sex on CVR in moderate/severe TBI. Future work in the field should focus on the impact of age and sex on multi-modal cerebral physiological monitoring.
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Project description:Much attention has been paid to the effects of mild traumatic brain injury (mTBI) on cerebrovascular reactivity in adult populations, yet it remains understudied in pediatric injury. In this study, 30 adolescents (12-18 years old) with pediatric mTBI (pmTBI) and 35 age- and sex-matched healthy controls (HC) underwent clinical and neuroimaging assessments during sub-acute (6.9 ± 2.2 days) and early chronic (120.4 ± 11.7 days) phases of injury. Relative to controls, pmTBI reported greater initial post-concussion symptoms, headache, pain, and anxiety, resolving by four months post-injury. Patients reported increased sleep issues and exhibited deficits in processing speed and attention across both visits. In grey-white matter interface areas throughout the brain, pmTBI displayed increased maximal fit/amplitude of a time-shifted end-tidal CO2 regressor to blood oxygen-level dependent response relative to HC, as well as increased latency to maximal fit. The alterations persisted through the early chronic phase of injury, with maximal fit being associated with complaints of ongoing sleep disturbances during post hoc analyses but not cognitive measures of processing speed or attention. Collectively, these findings suggest that deficits in the speed and degree of cerebrovascular reactivity may persist longer than current conceptualizations about clinical recovery within 30 days.
| S-EPMC7820694 | biostudies-literature
Project description:Injury to the neurovasculature is a feature of brain injury and must be addressed to maximize opportunity for improvement. Cerebrovascular dysfunction, manifested by reduction in cerebral blood flow (CBF), is a key factor that worsens outcome after traumatic brain injury (TBI), most notably under conditions of hypotension. We report here that a new class of antioxidants, poly(ethylene glycol)-functionalized hydrophilic carbon clusters (PEG-HCCs), which are nontoxic carbon particles, rapidly restore CBF in a mild TBI/hypotension/resuscitation rat model when administered during resuscitation--a clinically relevant time point. Along with restoration of CBF, there is a concomitant normalization of superoxide and nitric oxide levels. Given the role of poor CBF in determining outcome, this finding is of major importance for improving patient health under clinically relevant conditions during resuscitative care, and it has direct implications for the current TBI/hypotension war-fighter victims in the Afghanistan and Middle East theaters. The results also have relevancy in other related acute circumstances such as stroke and organ transplantation.
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