Health Determinants among North Americans Experiencing Homelessness and Traumatic Brain Injury: A Scoping Review.

Traumatic brain injury (TBI) in those experiencing homelessness has been described in recent literature as a contributor to increased morbidity, decreased functional independence, and early mortality. In this systematically conducted scoping review, we aimed to better delineate the health determinants-as defined by Health Canada/Centers for Disease Control and Prevention (CDC)-associated with TBI in North Americans experiencing homelessness. BIOSIS, MEDLINE, CINAHL, EMBASE, SCOPUS, and Global Health were searched from inception to December 30, 2020. Gray literature search consisted of relevant meeting proceedings. A two-step process was undertaken, assessing title/abstract and full articles, respectively, based on inclusion/exclusion criteria, leading to the final 20 articles included in the review. Data were abstracted, assessing the aims, literature quality, and bias. Five health determinants displayed strong associations with TBI in those North Americans experiencing homelessness, including male gender, poor physical environment, negative personal health behaviors, adverse childhood experiences (ACEs), and low educational attainment. In those studies displaying a comparator population experiencing homelessness without TBI, the TBI group displayed trends toward increased disparity in Health Canada and CDC defined health determinants. Most studies suffered from moderate limitations. There are associations between male gender, poor physical environment, negative personal health behaviors, ACEs, and limited education in those experiencing homelessness and TBI. The results suggest that those experiencing homelessness with TBI in North America suffer poorer health consequences than those without TBI. Future research on TBI in North Americans experiencing homelessness should focus on health determinants as potential areas for intervention, which may lead to improved outcomes for those experiencing both homelessness and TBI

The effect of burst suppression on cerebral blood flow and autoregulation: a scoping review of the human and animal literature

Background: Burst suppression (BS) is an electroencephalography (EEG) pattern in which there are isoelectric periods interspersed with bursts of cortical activity. Targeting BS through anaesthetic administration is used as a tool in the neuro-intensive care unit but its relationship with cerebral blood flow (CBF) and cerebral autoregulation (CA) is unclear. We performed a systematic scoping review investigating the effect of BS on CBF and CA in animals and humans.Methods: We searched MEDLINE, BIOSIS, EMBASE, SCOPUS and Cochrane library from inception to August 2022. The data that were collected included study population, methods to induce and measure BS, and the effect on CBF and CA.Results: Overall, there were 66 studies that were included in the final results, 41 of which examined animals, 24 of which examined humans, and 1 of which examined both. In almost all the studies, BS was induced using an anaesthetic. In most of the animal and human studies, BS was associated with a decrease in CBF and cerebral metabolism, even if the mean arterial pressure remained constant. The effect on CA during periods of stress (hypercapnia, hypothermia, etc.) was variable.Discussion: BS is associated with a reduction in cerebral metabolic demand and CBF, which may explain its usefulness in patients with brain injury. More evidence is needed to elucidate the connection between BS and CA

High spatial and temporal resolution cerebrovascular reactivity for humans and large mammals: A technological description of integrated fNIRS and niABP mapping system

Introduction: The process of cerebral vessels maintaining cerebral blood flow (CBF) fairly constant over a wide range of arterial blood pressure is referred to as cerebral autoregulation (CA). Cerebrovascular reactivity is the mechanism behind this process, which maintains CBF through constriction and dilation of cerebral vessels. Traditionally CA has been assessed statistically, limited by large, immobile, and costly neuroimaging platforms. However, with recent technology advancement, dynamic autoregulation assessment is able to provide more detailed information on the evolution of CA over long periods of time with continuous assessment. Yet, to date, such continuous assessments have been hampered by low temporal and spatial resolution systems, that are typically reliant on invasive point estimations of pulsatile CBF or cerebral blood volume using commercially available technology.Methods: Using a combination of multi-channel functional near-infrared spectroscopy and non-invasive arterial blood pressure devices, we were able to create a system that visualizes CA metrics by converting them to heat maps drawn on a template of human brain.Results: The custom Python heat map module works in “offline” mode to visually portray the CA index per channel with the use of colourmap. The module was tested on two different mapping grids, 8 channel and 24 channel, using data from two separate recordings and the Python heat map module was able read the CA indices file and represent the data visually at a preselected rate of 10 s.Conclusion: The generation of the heat maps are entirely non-invasive, with high temporal and spatial resolution by leveraging the recent advances in NIRS technology along with niABP. The CA mapping system is in its initial stage and development plans are ready to transform it from “offline” to real-time heat map generation

Midline Shift is Unrelated to Subjective Pupillary Reactivity Assessment on Admission in Moderate and Severe Traumatic Brain Injury.

BACKGROUND: This study aims to determine the relationship between pupillary reactivity, midline shift and basal cistern effacement on brain computed tomography (CT) in moderate-to-severe traumatic brain injury (TBI). All are important diagnostic and prognostic measures, but their relationship is unclear. METHODS: A total of 204 patients with moderate-to-severe TBI, documented pupillary reactivity, and archived neuroimaging were included. Extent of midline shift and basal cistern effacement were extracted from admission brain CT. Mean midline shift was calculated for each ordinal category of pupillary reactivity and basal cistern effacement. Sequential Chi-square analysis was used to calculate a threshold midline shift for pupillary abnormalities and basal cistern effacement. Univariable and multiple logistic regression analyses were performed. RESULTS: Pupils were bilaterally reactive in 163 patients, unilaterally reactive in 24, and bilaterally unreactive in 17, with mean midline shift (mm) of 1.96, 3.75, and 2.56, respectively (p = 0.14). Basal cisterns were normal in 118 patients, compressed in 45, and absent in 41, with mean midline shift (mm) of 0.64, 2.97, and 5.93, respectively (p < 0.001). Sequential Chi-square analysis identified a threshold for abnormal pupils at a midline shift of 7-7.25 mm (p = 0.032), compressed basal cisterns at 2 mm (p < 0.001), and completely effaced basal cisterns at 7.5 mm (p < 0.001). Logistic regression revealed no association between midline shift and pupillary reactivity. With effaced basal cisterns, the odds ratio for normal pupils was 0.22 (95% CI 0.08-0.56; p = 0.0016) and for at least one unreactive pupil was 0.061 (95% CI 0.012-0.24; p < 0.001). Basal cistern effacement strongly predicted midline shift (OR 1.27; 95% CI 1.17-1.40; p < 0.001). CONCLUSIONS: Basal cistern effacement alone is associated with pupillary reactivity and is closely associated with midline shift. It may represent a uniquely useful neuroimaging marker to guide intervention in traumatic brain injury

Current state of high-fidelity multimodal monitoring in traumatic brain injury

Introduction Multimodality monitoring of patients with severe traumatic brain injury (TBI) is primarily performed in neurocritical care units to prevent secondary harmful brain insults and facilitate patient recovery. Several metrics are commonly monitored using both invasive and non-invasive techniques. The latest Brain Trauma Foundation guidelines from 2016 provide recommendations and thresholds for some of these. Still, high-level evidence for several metrics and thresholds is lacking. Methods Regarding invasive brain monitoring, intracranial pressure (ICP) forms the cornerstone, and pressures above 22 mmHg should be avoided. From ICP, cerebral perfusion pressure (CPP) (mean arterial pressure (MAP)-ICP) and pressure reactivity index (PRx) (a correlation between slow waves MAP and ICP as a surrogate for cerebrovascular reactivity) may be derived. In terms of regional monitoring, partial brain tissue oxygen pressure (PbtO(2)) is commonly used, and phase 3 studies are currently ongoing to determine its added effect to outcome together with ICP monitoring. Cerebral microdialysis (CMD) is another regional invasive modality to measure substances in the brain extracellular fluid. International consortiums have suggested thresholds and management strategies, in spite of lacking high-level evidence. Although invasive monitoring is generally safe, iatrogenic hemorrhages are reported in about 10% of cases, but these probably do not significantly affect long-term outcome. Non-invasive monitoring is relatively recent in the field of TBI care, and research is usually from single-center retrospective experiences. Near-infrared spectrometry (NIRS) measuring regional tissue saturation has been shown to be associated with outcome. Transcranial doppler (TCD) has several tentative utilities in TBI like measuring ICP and detecting vasospasm. Furthermore, serial sampling of biomarkers of brain injury in the blood can be used to detect secondary brain injury development. Conclusions In multimodal monitoring, the most important aspect is data interpretation, which requires knowledge of each metric's strengths and limitations. Combinations of several modalities might make it possible to discern specific pathologic states suitable for treatment. However, the cost-benefit should be considered as the incremental benefit of adding several metrics has a low level of evidence, thus warranting additional research.Peer reviewe

Compensatory-reserve-weighted intracranial pressure versus intracranial pressure for outcome association in adult traumatic brain injury : a CENTER-TBI validation study

BackgroundCompensatory-reserve-weighted intracranial pressure (wICP) has recently been suggested as a supplementary measure of intracranial pressure (ICP) in adult traumatic brain injury (TBI), with a single-center study suggesting an association with mortality at 6months. No multi-center studies exist to validate this relationship. The goal was to compare wICP to ICP for association with outcome in a multi-center TBI cohort.MethodsUsing the Collaborative European Neuro Trauma Effectiveness Research in TBI (CENTER-TBI) high-resolution intensive care unit (ICU) cohort, we derived ICP and wICP (calculated as wICP=(1-RAP)xICP; where RAP is the compensatory reserve index derived from the moving correlation between pulse amplitude of ICP and ICP). Various univariate logistic regression models were created comparing ICP and wICP to dichotomized outcome at 6 to 12months, based on Glasgow Outcome ScoreExtended (GOSE) (alive/deadGOSE 2/GOSE=1; favorable/unfavorableGOSE 5 to 8/GOSE 1 to 4, respectively). Models were compared using area under the receiver operating curves (AUC) and p values.ResultswICP displayed higher AUC compared to ICP on univariate regression for alive/dead outcome compared to mean ICP (AUC 0.712, 95% CI 0.615-0.810, p=0.0002, and AUC 0.642, 95% CI 0.538-746, pPeer reviewe

The cerebrovascular response to norepinephrine: A scoping systematic review of the animal and human literature.

Funder: CIHRFunder: NINDS NIH HHSIntravenous 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

Cerebrovascular Response to Phenylephrine in Traumatic Brain Injury: A Scoping Systematic Review of the Human and Animal Literature.

Intravenous phenylephrine (PE) is utilized commonly in critical care for cardiovascular support. Its impact on the cerebrovasculature is unclear and its use may have important implications during states of critical neurological illness. The aim of this study was to perform a scoping review of the literature on the cerebrovascular/cerebral blood flow (CBF) effects of PE in traumatic brain injury (TBI), evaluating both animal models and human studies. We searched MEDLINE, BIOSIS, EMBASE, Global Health, SCOPUS, and the Cochrane Library from inception to January 2020. We identified 12 studies with various animal models and 4 studies in humans with varying TBI pathology. There was a trend toward a consistent increase in mean arterial pressure (MAP) by the injection of PE systemically, and by proxy, an increase of the cerebral perfusion pressure (CPP). There was a consistent constriction of cerebral vessels by PE reported in the small number of studies documenting such a response. However, the heterogeneity of the literature on the CBF/cerebral blood volume (CBV) response makes the strength of the conclusions on PE limited. Studies were heterogeneous in design and had significant limitations, with most failing to adjust for confounding factors in cerebrovascular/CBF response. This review highlights the significant knowledge gap on the cerebrovascular/CBF effects of PE administration in TBI, calling for further study on the impact of PE on the cerebrovasculature both in vivo and in experimental settings

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

Background: Disruption in cerebrovascular reactivity following traumatic brain injury (TBI) is a known phenomenon that may hold prognostic value and clinical relevance. Ultimately, improved knowledge of this process and more robust means of continuous assessment may lead to advances in precision medicine following TBI. One such method is transcranial Doppler (TCD), which has been employed to evaluate cerebrovascular reactivity following injury utilizing a continuous time-series approach. Objective: The present study undertakes a scoping review of the literature on the association of continuous time-domain TCD based indices of cerebrovascular reactivity, with global functional outcomes, cerebral physiologic correlates, and imaging evidence of lesion change. Design: Multiple databases were searched from inception to November 2020 for articles relevant to the association of continuous time-domain TCD based indices of cerebrovascular reactivity with global functional outcomes, cerebral physiologic correlates, and imaging evidence of lesion change. Results: Thirty-six relevant articles were identified. There was significant evidence supporting an association with continuous time-domain TCD based indices and functional outcomes following TBI. Indices based on mean flow velocity, as measured by TCD, were most numerous while more recent studies point to systolic flow velocity-based indices encoding more prognostic utility. Physiologic parameters such as intracranial pressure, cerebral perfusion pressure, Carbon Dioxide (CO2) reactivity as well as more established indices of cerebrovascular reactivity have all been associated with these TCD based indices. The literature has been concentrated in a few centres and is further limited by the lack of multivariate analysis. Conclusions: This systematic scoping review of the literature identifies that there is a substantial body of evidence that cerebrovascular reactivity as measured by time-domain TCD based indices have prognostic utility following TBI. Indices based on mean flow velocities have the largest body of literature for their support. However, recent studies indicate that indices based on systolic flow velocities may contain the most prognostic utility and more closely follow more established measures of cerebrovascular reactivity. To a lesser extent, the literature supports some associations between these indices and cerebral physiologic parameters. These indices provide a more complete picture of the patient's physiome following TBI and may ultimately lead to personalized and precise clinical care. Further validation in multi-institution studies is required before these indices can be widely adopted clinically