Search

Objective . Intracranial pressure measurement (ICP) is an essential component of deriving of multivariate data metrics foundational to improving understanding of high temporal relationships in cerebral physiology. A significant barrier to this work is artifact ridden data. As such, the objective of this review was to examine the existing literature pertinent to ICP artifact management. Methods. A search of five databases (BIOSIS, SCOPUS, EMBASE, PubMed, and Cochrane Library) was conducted based on the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines with the PRISMA Extension for Scoping Review. The search question examined the methods for artifact management for ICP signals measured in human/animals. Results. The search yielded 5875 unique results. There were 19 articles included in this review based on inclusion/exclusion criteria and article references. Each method presented was categorized as: (1) valid ICP pulse detection algorithms and (2) ICP artifact identification and removal methods. Machine learning-based and filter-based methods indicated the best results for artifact management; however, it was not possible to elucidate a single most robust method. Conclusion. There is a significant lack of standardization in the metrics of effectiveness in artifact removal which makes comparison difficult across studies. Differences in artifacts observed on patient neuropathological health and recording methodologies have not been thoroughly examined and introduce additional uncertainty regarding effectiveness. Significance . This work provides critical insights into existing literature pertaining to ICP artifact management as it highlights holes in the literature that need to be adequately addressed in the establishment of robust artifact management methodologies., (Creative Commons Attribution license.)

Neurointensive care primarily focuses on secondary injury reduction, utilizing a variety of guideline-based approaches (including administration of high-dose sedation) to reduce the injured state. However, titration of sedation is currently based on the Richmond Agitation Sedation Scale (RASS), a subjective clinical grading score of a patient's response to external physical stimuli, and not an objective measure. Therefore, it is likely that there exists substantial variation in objective sedation depth for a given clinical grade in these patients, leading to undesired sedation depths and cerebral physiological consequences. Improper sedation can impede cerebral autoregulation, emphasizing the critical need for optimal sedation in traumatic brain injury (TBI) patients. This study evaluates the relationship between RASS to an objective measure of depth of sedation (bispectral index, BIS) and cerebral physiological measures. Fifty-nine patients were assessed using Jonckheere-Terpstra testing to compare various key physiologies with RASS. RASS (-5 through 0 categories) showed no statistically significant relationship between BIS and cerebral physiological parameters, after adjusting for multiple comparisons. Furthermore, it is crucial to note that within each RASS value, the distribution of the physiological measures all had high variability. As an exemplar, for RASS values of -5 and -4, BIS ranged from near 0 (burst suppression levels) up to over 80 (near awake states). BIS and other cerebral physiologies displayed substantial variation across each RASS category. This suggests that RASS as a means to titrate sedative medication for the goal of neuroprotection is insufficient. More momentary, individualized determination of sedation depth is required for TBI patients., (© The Author(s) 2024. Published by Mary Ann Liebert, Inc.)

Artifacts induced during patient monitoring are a main limitation for near-infrared spectroscopy (NIRS) as a non-invasive method of cerebral hemodynamic monitoring. There currently does not exist a robust "gold-standard" method for artifact management for these signals. The objective of this review is to comprehensively examine the literature on existing artifact management methods for cerebral NIRS signals recorded in animals and humans. A search of five databases was conducted based on the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. The search yielded 806 unique results. There were 19 articles from these results that were included in this review based on the inclusion/exclusion criteria. There were an additional 36 articles identified in the references of select articles that were also included. The methods outlined in these articles were grouped under two major categories: (1) motion and other disconnection artifact removal methods; (2) data quality improvement and physiological/other noise artifact filtering methods. These were sub-categorized by method type. It proved difficult to quantitatively compare the methods due to the heterogeneity of the effectiveness metrics and definitions of artifacts. The limitations evident in the existing literature justify the need for more comprehensive comparisons of artifact management. This review provides insights into the available methods for artifact management in cerebral NIRS and justification for a homogenous method to quantify the effectiveness of artifact management methods. This builds upon the work of two existing reviews that have been conducted on this topic; however, the scope is extended to all artifact types and all NIRS recording types. Future work by our lab in cerebral NIRS artifact management will lie in a layered artifact management method that will employ different techniques covered in this review (including dynamic thresholding, autoregressive-based methods, and wavelet-based methods) amongst others to remove varying artifact types.

Acute traumatic neural injury, known as traumatic brain injury (TBI), stands as a significant contributor to global mortality and disability. Ideally, continuously monitoring cerebral compliance/cerebral compensatory reserve would enable timely interventions and avert further substantial deterioration in TBI cases. RAP, defined as the moving Pearson's correlation between intracranial pressure (ICP) pulse amplitude waveform and ICP, has been proposed as a continuously updating index in this context. However, the literature remains scattered and difficult to navigate. Thus, the goal of this scoping review was to comprehensively characterize the literature regarding RAP and its association with (1) other multimodal cerebral physiological monitoring, (2) neuroimaging features, and (3) long-term patient outcomes. We subsequently conducted a systematic scoping review of the human literature to highlight the association of RAP with continuous multimodal monitoring of cerebral physiology, neuroimaging, and patient outcomes in the context of adult TBI patients. Our review encompassed 21 studies focusing on these topics. The primary findings involve meticulous analysis of studies, categorizing findings into three states of RAP to clearly understand its relation to cerebral physiology and clinical outcomes. State 1 signifies a healthy condition with a small positive value near zero (RAP <0.5). Conversely, state 2, a predominant characterization of TBI patients, indicates compromised compensatory reserve, featuring a large positive RAP value (RAP > 0.4). State 3 emerges in worsened conditions, showcasing further compromised compensatory reserve, exhausted cerebrovascular reactivity, and disturbed cerebral autoregulation. A substantial number of patients with fatal outcomes was found in state 3, marked by a notable occurrence of decreasing and, in some instances, negative RAP. The significance of this review lies in establishing a platform for future research directions to enhance the precision and clinical implications of RAP in TBI care, ultimately aiming to prevent the transition from state 2 to state 3 and mitigate fatal outcomes., (© The Author(s) 2024. Published by Mary Ann Liebert, Inc.)

Global outcomes have been reported to be associated with cerebrovascular reactivity (CVR) in the acute phase following moderate and severe traumatic brain injury (TBI). The association of CVR in the acute and chronic phase of injury with patient-reported health-related quality of life metrics (HRQOL) metrics has never been explored. The aim of this study is to examine the association of CVR, as measured by the cerebral oxygen indices (COx and COx&#95;a), in the acute and chronic phase following moderate and severe TBI, with patient reported HRQOL. In this prospective cohort study, performed in a Canadian quaternary care center, the association between continuous acute and chronic phase CVR with patient reported HRQOL outcomes following moderate and severe TBI was examined. The main outcomes of interest of this study were validated measures of patient-reported HRQOL over various domains as measured by both the 12-Item Short-Form Health Survey (SF-12) and a Quality of Life after Brain Injury (QOLIBRI) questionnaire. In the 29 subjects of this cohort, acute phase CVR was found to be significantly more active in those with a favorable Mental Component Summary (MCS) scores of the SF-12 at early follow-up when measured by COx (-0.015 [IQR: -0.067 to 0.032] vs 0.040 [IQR: 0.019 to 0.137] for Favorable first MCS vs Unfavorable respectively; Mann-Whitney U test p-value = 0.046) and COx&#95;a (0.038 [IQR: 0.009 to 0.062] vs 0.112 [IQR: 0.065 to 0.167] for Favorable first MCS vs Unfavorable respectively; Mann-Whitney U test p-value = 0.014). Further, multivariable logistic regression analysis found acute phase COx and COx&#95;a to improve model performance when predicting favorable versus unfavorable early MCS scores over established parameters such as age and measures of injury severity. Associations between outcomes and chronic phase CVR were limited, potentially due to short recording periods. This is the first ever pilot study to identify a relationship between acute phase CVR following moderate-to-severe TBI with mental and cognitive outcomes as experienced by patients. Given the small cohort, these findings will need to be confirmed in a larger multicenter study. This highlights the need for additional examination of the role dysfunctional CVR may play in mental and cognitive outcomes, as well as patient-reported outcomes more generally following TBI., (© 2024. The Author(s).)

Background: Over the recent decades, continuous multi-modal monitoring of cerebral physiology has gained increasing interest for its potential to help minimize secondary brain injury following moderate-to-severe acute traumatic neural injury (also termed traumatic brain injury; TBI). Despite this heightened interest, there has yet to be a comprehensive evaluation of the effects of derangements in multimodal cerebral physiology on global cerebral physiologic insult burden. In this study, we offer a multi-center descriptive analysis of the associations between deranged cerebral physiology and cerebral physiologic insult burden., Methods: Using data from the Canadian High-Resolution TBI (CAHR-TBI) Research Collaborative, a total of 369 complete patient datasets were acquired for the purposes of this study. For various cerebral physiologic metrics, patients were trichotomized into low, intermediate, and high cohorts based on mean values. Jonckheere-Terpstra testing was then used to assess for directional relationships between these cerebral physiologic metrics and various measures of cerebral physiologic insult burden. Contour plots were then created to illustrate the impact of preserved vs impaired cerebrovascular reactivity on these relationships., Results: It was found that elevated intracranial pressure (ICP) was associated with more time spent with cerebral perfusion pressure (CPP) < 60 mmHg and more time with impaired cerebrovascular reactivity. Low CPP was associated with more time spent with ICP > 20 or 22 mmHg and more time spent with impaired cerebrovascular reactivity. Elevated cerebrovascular reactivity indices were associated with more time spent with CPP < 60 mmHg as well as ICP > 20 or 22 mmHg. Low brain tissue oxygenation (PbtO 2 ) only demonstrated a significant association with more time spent with CPP < 60 mmHg. Low regional oxygen saturation (rSO 2 ) failed to produce a statistically significant association with any particular measure of cerebral physiologic insult burden., Conclusions: Mean ICP, CPP and, cerebrovascular reactivity values demonstrate statistically significant associations with global cerebral physiologic insult burden; however, it is uncertain whether measures of oxygen delivery provide any significant insight into such insult burden., (© 2024. The Author(s).)

Purpose: Continuous cerebrovascular reactivity monitoring in both neurocritical and intra-operative care has gained extensive interest in recent years, as it has documented associations with long-term outcomes (in neurocritical care populations) and cognitive outcomes (in operative cohorts). This has sparked further interest into the exploration and evaluation of methods to achieve an optimal cerebrovascular reactivity measure, where the individual patient is exposed to the lowest insult burden of impaired cerebrovascular reactivity. Recent literature has documented, in neural injury populations, the presence of a potential optimal sedation level in neurocritical care, based on the relationship between cerebrovascular reactivity and quantitative depth of sedation (using bispectral index (BIS)) - termed BISopt. The presence of this measure outside of neural injury patients has yet to be proven., Methods: We explore the relationship between BIS and continuous cerebrovascular reactivity in two cohorts: (A) healthy population undergoing elective spinal surgery under general anesthesia, and (B) healthy volunteer cohort of awake controls., Results: We demonstrate the presence of BISopt in the general anesthesia population (96% of patients), and its absence in awake controls, providing preliminary validation of its existence outside of neural injury populations. Furthermore, we found BIS to be sufficiently separate from overall systemic blood pressure, this indicates that they impact different pathophysiological phenomena to mediate cerebrovascular reactivity., Conclusions: Findings here carry implications for the adaptation of the individualized physiologic BISopt concept to non-neural injury populations, both within critical care and the operative theater. However, this work is currently exploratory, and future work is required., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Traumatic brain injury (TBI) poses a significant global public health challenge necessitating a profound understanding of cerebral physiology. The dynamic nature of TBI demands sophisticated methodologies for modeling and predicting cerebral signals to unravel intricate pathophysiology and predict secondary injury mechanisms prior to their occurrence. In this comprehensive scoping review, we focus specifically on multivariate cerebral physiologic signal analysis in the context of multi-modal monitoring (MMM) in TBI, exploring a range of techniques including multivariate statistical time-series models and machine learning algorithms. Conducting a comprehensive search across databases yielded 7 studies for evaluation, encompassing diverse cerebral physiologic signals and parameters from TBI patients. Among these, five studies concentrated on modeling cerebral physiologic signals using statistical time-series models, while the remaining two studies primarily delved into intracranial pressure (ICP) prediction through machine learning models. Autoregressive models were predominantly utilized in the modeling studies. In the context of prediction studies, logistic regression and Gaussian processes (GP) emerged as the predominant choice in both research endeavors, with their performance being evaluated against each other in one study and other models such as random forest, and decision tree in the other study. Notably among these models, random forest model, an ensemble learning approach, demonstrated superior performance across various metrics. Additionally, a notable gap was identified concerning the absence of studies focusing on prediction for multivariate outcomes. This review addresses existing knowledge gaps and sets the stage for future research in advancing cerebral physiologic signal analysis for neurocritical care improvement., Competing Interests: Declaration of competing interest The authors assert that they have no conflicts of interest to disclose regarding this work, confirming the absence of any financial interests, affiliations, or personal relationships that may have influenced or biased this research., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Moderate-to-severe traumatic brain injury (TBI) has a global mortality rate of about 30%, resulting in acquired life-long disabilities in many survivors. To potentially improve outcomes in this TBI population, the management of secondary injuries, particularly the failure of cerebrovascular reactivity (assessed via the pressure reactivity index; PRx, a correlation between intracranial pressure (ICP) and mean arterial blood pressure (MAP)), has gained interest in the field. However, derivation of PRx requires high-resolution data and expensive technological solutions, as calculations use a short time-window, which has resulted in it being used in only a handful of centers worldwide. As a solution to this, low resolution (longer time-windows) PRx has been suggested, known as Long-PRx or LPRx. Though LPRx has been proposed little is known about the best methodology to derive this measure, with different thresholds and time-windows proposed. Furthermore, the impact of ICP monitoring on cerebrovascular reactivity measures is poorly understood. Hence, this observational study establishes critical thresholds of LPRx associated with long-term functional outcome, comparing different time-windows for calculating LPRx as well as evaluating LPRx determined through external ventricular drains (EVD) vs intraparenchymal pressure device (IPD) ICP monitoring., Methods: The study included a total of n = 435 TBI patients from the Karolinska University Hospital. Patients were dichotomized into alive vs. dead and favorable vs. unfavorable outcomes based on 1-year Glasgow Outcome Scale (GOS). Pearson's chi-square values were computed for incrementally increasing LPRx or ICP thresholds against outcome. The thresholds that generated the greatest chi-squared value for each LPRx or ICP parameter had the highest outcome discriminatory capacity. This methodology was also completed for the segmentation of the population based on EVD, IPD, and time of data recorded in hospital stay., Results: LPRx calculated with 10-120-min windows behaved similarly, with maximal chi-square values ranging at around a LPRx of 0.25-0.35, for both survival and favorable outcome. When investigating the temporal relations of LPRx derived thresholds, the first 4 days appeared to be the most associated with outcomes. The segmentation of the data based on intracranial monitoring found limited differences between EVD and IPD, with similar LPRx values around 0.3., Conclusion: Our work suggests that the underlying prognostic factors causing impairment in cerebrovascular reactivity can, to some degree, be detected using lower resolution PRx metrics (similar found thresholding values) with LPRx found clinically using as low as 10 min-by-minute samples of MAP and ICP. Furthermore, EVD derived LPRx with intermittent cerebrospinal fluid draining, seems to present similar outcome capacity as IPD. This low-resolution low sample LPRx method appears to be an adequate substitute for the clinical prognostic value of PRx and may be implemented independent of ICP monitoring method when PRx is not feasible, though further research is warranted., (© 2024. The Author(s).)

Objective. Continuous monitoring of cerebrospinal compliance (CC) / cerebrospinal compensatory reserve (CCR) is crucial for timely interventions and preventing more substantial deterioration in the context of acute neural injury, as it enables the early detection of abnormalities in intracranial pressure (ICP). However, to date, the literature on continuous CC/CCR monitoring is scattered and occasionally challenging to consolidate. Approach. We subsequently conducted a systematic scoping review of the human literature to highlight the available continuous CC/CCR monitoring methods. Main results. This systematic review incorporated a total number of 76 studies, covering diverse patient types and focusing on three primary continuous CC or CCR monitoring metrics and methods-Moving Pearson's correlation between ICP pulse amplitude waveform and ICP, referred to as RAP, the Spiegelberg Compliance Monitor, changes in cerebral blood flow velocity with respect to the alternation of ICP measured through transcranial doppler (TCD), changes in centroid metric, high frequency centroid (HFC) or higher harmonics centroid (HHC), and the P2/P1 ratio which are the distinct peaks of ICP pulse wave. The majority of the studies in this review encompassed RAP metric analysis ( n = 43), followed by Spiegelberg Compliance Monitor ( n = 11), TCD studies ( n = 9), studies on the HFC/HHC ( n = 5), and studies on the P2/P1 ratio studies ( n = 6). These studies predominantly involved acute traumatic neural injury (i.e. Traumatic Brain Injury) patients and those with hydrocephalus. RAP is the most extensively studied of the five focused methods and exhibits diverse applications. However, most papers lack clarification on its clinical applicability, a circumstance that is similarly observed for the other methods. Significance. Future directions involve exploring RAP patterns and identifying characteristics and artifacts, investigating neuroimaging correlations with continuous CC/CCR and integrating machine learning, holding promise for simplifying CC/CCR determination. These approaches should aim to enhance the precision and accuracy of the metric, making it applicable in clinical practice., (Creative Commons Attribution license.)

Importance: Microvascular autoregulation (MA) maintains adequate tissue perfusion over a range of arterial blood pressure (ABP) and is frequently impaired in critical illness. MA has been studied in the brain to derive personalized hemodynamic targets after brain injury. The ability to measure MA in other organs is not known, which may inform individualized management during shock., Objectives: This study determines the feasibility of measuring MA in skeletal muscle using near-infrared spectroscopy (NIRS) as a marker of tissue perfusion, the derivation of optimal mean arterial pressure (MAPopt), and comparison with indices from the brain., Design: Prospective observational study., Setting: Medical and surgical ICU in a tertiary academic hospital., Participants: Adult critically ill patients requiring vasoactive support on the first day of ICU admission., Main Outcomes and Measures: Fifteen critically ill patients were enrolled. NIRS was applied simultaneously to skeletal muscle (brachioradialis) and brain (frontal cortex) while ABP was measured continuously via invasive catheter. MA correlation indices were calculated between ABP and NIRS from skeletal muscle total hemoglobin (MVx), muscle tissue saturation index (MOx), brain total hemoglobin (THx), and brain tissue saturation index (COx). Curve fitting algorithms derive the MAP with the lowest correlation index value, which is the MAPopt., Results: MAPopt values were successfully calculated for each correlation index for all patients and were frequently (77%) above 65 mm Hg. For all correlation indices, median time was substantially above impaired MA threshold (24.5-34.9%) and below target MAPopt (9.0-78.6%). Muscle and brain MAPopt show moderate correlation (MVx-THx r = 0.76, p < 0.001; MOx-COx r = 0.69, p = 0.005), with a median difference of -1.27 mm Hg (-9.85 to -0.18 mm Hg) and 0.05 mm Hg (-7.05 to 2.68 mm Hg)., Conclusions and Relevance: This study demonstrates, for the first time, the feasibility of calculating MA indices and MAPopt in skeletal muscle using NIRS. Future studies should explore the association between impaired skeletal muscle MA, ICU outcomes, and organ-specific differences in MA and MAPopt thresholds., Competing Interests: Dr. Mendelson receives research support from the Manitoba Medical Services Foundation Dr. F. W. DuVal and John Henson Clinical Research Professorship. Drs. Mendelson and Zeiler have funding, that is, unrelated to this current project from the Health Sciences Centre Foundation (Winnipeg), the Canadian Institutes of Health Research (CIHR), the Canada Foundation for Innovation, and the Research Manitoba. Dr. Gomez is supported by the CIHR Fellowship program. Mr. Singh Sainbhi is supported by the University of Manitoba Graduate Fellowship in Biomedical Engineering—Doctoral Stream. Dr. Froese is supported through the Natural Sciences and Engineering Research Council of Canada (NSERC) Post-Doctoral Fellowship program. Dr. Zeiler is supported through the University of Manitoba Endowed Manitoba Public Insurance Chair in Neuroscience and the NSERC (DGECR-2022-00260, RGPIN-2022-03621, ALLRP-578524-22, ALLRP-576386-22, ALLRP-586244-23, I2IPJ 586104–23). Dr. Zarychanski receives research support from the Lyonel G. Israels Endowed Research Chair in Hematology, University of Manitoba; he has funding, that is, unrelated to the current project from the CIHR. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)

Cerebrovascular pressure reactivity plays a key role in maintaining constant cerebral blood flow. Unfortunately, this mechanism is often impaired in acute traumatic neural injury states, exposing the already injured brain to further pressure-passive insults. While there has been much work on the association between impaired cerebrovascular reactivity following moderate/severe traumatic brain injury (TBI) and worse long-term outcomes, there is yet to be a comprehensive review on the association between cerebrovascular pressure reactivity and intracranial pressure (ICP) extremes. Therefore, we conducted a systematic review of the literature for all studies presenting a quantifiable statistical association between a continuous measure of cerebrovascular pressure reactivity and ICP in a human TBI cohort. The methodology described in the Cochrane Handbook for Systematic Reviews was used. BIOSIS, Cochrane Library, EMBASE, Global Health, MEDLINE, and SCOPUS were all searched from their inceptions to March of 2023 for relevant articles. Full-length original works with a sample size of ≥10 patients with moderate/severe TBI were included in this review. Data were reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. A total of 16 articles were included in this review. Studies varied in population characteristics and statistical tests used. Five studies looked at transcranial Doppler-based indices and 13 looked at ICP-based indices. All but two studies were able to present a statistically significant association between cerebrovascular pressure reactivity and ICP. Based on the findings of this review, impaired reactivity seems to be associated with elevated ICP and reduced ICP waveform complexity. This relationship may allow for the calculation of patient-specific ICP thresholds, past which cerebrovascular reactivity becomes persistently deranged. However, further work is required to better understand this relationship and improve algorithmic derivation of such individualized ICP thresholds., (© Kevin Y. Stein et al. 2024; Published by Mary Ann Liebert, Inc.)

Current neurointensive care guidelines recommend intracranial pressure (ICP) and cerebral perfusion pressure (CPP) centered management for moderate-severe traumatic brain injury (TBI) because of their demonstrated associations with patient outcome. Cerebrovascular reactivity metrics, such as the pressure reactivity index (PRx), pulse amplitude index (PAx), and RAC index, have also demonstrated significant prognostic capabilities with regard to outcome. However, critical thresholds for cerebrovascular reactivity indices have only been identified in two studies conducted at the same center. In this study, we aim to determine the critical thresholds of these metrics by leveraging a unique multi-center database. The study included a total of 354 patients from the CAnadian High-Resolution TBI (CAHR-TBI) Research Collaborative. Based on 6-month Glasgow Outcome Scores, patients were dichotomized into alive versus dead and favorable versus unfavorable. Chi-square values were then computed for incrementally increasing values of each physiological parameter of interest against outcome. The values that generated the greatest chi-squares for each parameter were considered to be the thresholds with the greatest outcome discriminatory capacity. To confirm that the identified thresholds provide prognostic utility, univariate and multivariable logistical regression analyses were performed adjusting for the International Mission for Prognosis and Analysis of Clinical Trials (IMPACT) variables. Through the chi-square analysis, a lower limit CPP threshold of 60 mm Hg and ICP thresholds of 18 mm Hg and 22 mm Hg were identified for both survival and favorable outcome predictions. For the cerebrovascular reactivity metrics, different thresholds were identified for the two outcome dichotomizations. For survival prediction, thresholds of 0.35, 0.25, and 0 were identified for PRx, PAx, and RAC, respectively. For favorable outcome prediction, thresholds of 0.325, 0.20, and 0.05 were found. Univariate logistical regression analysis demonstrated that the time spent above/below thresholds were associated with outcome. Further, multivariable logistical regression analysis found that percent time above/below the identified thresholds added additional variance to the IMPACT core model for predicting both survival and favorable outcome. In this study, we were able to validate the results of the previous two works as well as to reaffirm the ICP and CPP guidelines from the Brain Trauma Foundation (BTF) and the Seattle International Severe Traumatic Brain Injury Consensus Conference (SIBICC).

Near-infrared spectroscopy (NIRS) regional cerebral oxygen saturation (rSO 2 )-based cerebrovascular reactivity (CVR) monitoring has enabled entirely non-invasive, continuous monitoring during both acute and long-term phases of care. To date, long-term post-injury CVR has not been properly characterized after acute traumatic neural injury, also known as traumatic brain injury (TBI). This study aims to compare CVR in those recovering from moderate-to-severe TBI with a healthy control group. A total of 101 heathy subjects were recruited for this study, along with 29 TBI patients. In the healthy cohort, the arterial blood pressure variant of the cerebral oxygen index (COx&#95;a) was not statistically different between males and females or in the dominant and non-dominant hemispheres. In the TBI cohort, COx&#95;a was not statistically different between the first and last available follow-up or by the side of cranial surgery. Surprisingly, CVR, as measured by COx&#95;a, was statistically better in those recovering from TBI than those in the healthy cohort. In this prospective cohort study, CVR, as measured by NIRS-based methods, was found to be more active in those recovering from TBI than in the healthy cohort. This study may indicate that in individuals that survive TBI, CVR may be enhanced as a neuroprotective measure.

Background: Near-infrared spectroscopy regional cerebral oxygen saturation (rSO 2 ) has gained interest as a raw parameter and as a basis for measuring cerebrovascular reactivity (CVR) due to its noninvasive nature and high spatial resolution. However, the prognostic utility of these parameters has not yet been determined. This study aimed to identify threshold values of rSO 2 and rSO 2 -based CVR at which outcomes worsened following traumatic brain injury (TBI)., Methods: A retrospective multi-institutional cohort study was performed. The cohort included TBI patients treated in four adult intensive care units (ICU). The cerebral oxygen indices, COx (using rSO 2 and cerebral perfusion pressure) as well as COx&#95;a (using rSO 2 and arterial blood pressure) were calculated for each patient. Grand mean thresholds along with exposure-based thresholds were determined utilizing sequential chi-squared analysis and univariate logistic regression, respectively., Results: In the cohort of 129 patients, there was no identifiable threshold for raw rSO 2 at which outcomes were found to worsen. For both COx and COx&#95;a, an optimal grand mean threshold value of 0.2 was identified for both survival and favorable outcomes, while percent time above - 0.05 was uniformly found to have the best discriminative value., Conclusions: In this multi-institutional cohort study, raw rSO 2 was found to contain no significant prognostic information. However, rSO 2 -based indices of CVR, COx and COx&#95;a, were found to have a uniform grand mean threshold of 0.2 and exposure-based threshold of - 0.05, above which clinical outcomes markedly worsened. This study lays the groundwork to transition to less invasive means of continuously measuring CVR., (© 2024. The Author(s).)

The modeling and forecasting of cerebral pressure-flow dynamics in the time-frequency domain have promising implications for veterinary and human life sciences research, enhancing clinical care by predicting cerebral blood flow (CBF)/perfusion, nutrient delivery, and intracranial pressure (ICP)/compliance behavior in advance. Despite its potential, the literature lacks coherence regarding the optimal model type, structure, data streams, and performance. This systematic scoping review comprehensively examines the current landscape of cerebral physiological time-series modeling and forecasting. It focuses on temporally resolved cerebral pressure-flow and oxygen delivery data streams obtained from invasive/non-invasive cerebral sensors. A thorough search of databases identified 88 studies for evaluation, covering diverse cerebral physiologic signals from healthy volunteers, patients with various conditions, and animal subjects. Methodologies range from traditional statistical time-series analysis to innovative machine learning algorithms. A total of 30 studies in healthy cohorts and 23 studies in patient cohorts with traumatic brain injury (TBI) concentrated on modeling CBFv and predicting ICP, respectively. Animal studies exclusively analyzed CBF/CBFv. Of the 88 studies, 65 predominantly used traditional statistical time-series analysis, with transfer function analysis (TFA), wavelet analysis, and autoregressive (AR) models being prominent. Among machine learning algorithms, support vector machine (SVM) was widely utilized, and decision trees showed promise, especially in ICP prediction. Nonlinear models and multi-input models were prevalent, emphasizing the significance of multivariate modeling and forecasting. This review clarifies knowledge gaps and sets the stage for future research to advance cerebral physiologic signal analysis, benefiting neurocritical care applications.

The contemporary monitoring of cerebrovascular reactivity (CVR) relies on invasive intracranial pressure (ICP) monitoring which limits its application. Interest is shifting towards near-infrared spectroscopic regional cerebral oxygen saturation (rSO 2 )-based indices of CVR which are less invasive and have improved spatial resolution. This study aims to examine and model the relationship between ICP and rSO 2 -based indices of CVR. Through a retrospective cohort study of prospectively collected physiologic data in moderate to severe traumatic brain injury (TBI) patients, linear mixed effects modeling techniques, augmented with time-series analysis, were utilized to evaluate the ability of rSO 2 -based indices of CVR to model ICP-based indices. It was found that rSO 2 -based indices of CVR had a statistically significant linear relationship with ICP-based indices, even when the hierarchical and autocorrelative nature of the data was accounted for. This strengthens the body of literature indicating the validity of rSO 2 -based indices of CVR and potential greatly expands the scope of CVR monitoring.

Regional cerebral oxygen saturation (rSO 2 ), a method of cerebral tissue oxygenation measurement, is recorded using non-invasive near-infrared Spectroscopy (NIRS) devices. A major limitation is that recorded signals often contain artifacts. Manually removing these artifacts is both resource and time consuming. The objective was to evaluate the applicability of using wavelet analysis as an automated method for simple signal loss artifact clearance of rSO 2 signals obtained from commercially available devices. A retrospective observational study using existing populations (healthy control (HC), elective spinal surgery patients (SP), and traumatic brain injury patients (TBI)) was conducted. Arterial blood pressure (ABP) and rSO 2 data were collected in all patients. Wavelet analysis was determined to be successful in removing simple signal loss artifacts using wavelet coefficients and coherence to detect signal loss artifacts in rSO 2 signals. The removal success rates in HC, SP, and TBI populations were 100%, 99.8%, and 99.7%, respectively (though it had limited precision in determining the exact point in time). Thus, wavelet analysis may prove to be useful in a layered approach NIRS signal artifact tool utilizing higher-frequency data; however, future work is needed.

Background: Optimal cerebral perfusion pressure (CPPopt) has emerged as a promising personalized medicine approach to the management of moderate-to-severe traumatic brain injury (TBI). Though literature demonstrating its association with poor outcomes exists, there is yet to be work done on its association with outcome transition due to a lack of serial outcome data analysis. In this study we investigate the association between various metrics of CPPopt and failure to improve in outcome over time., Methods: CPPopt was derived using three different cerebrovascular reactivity indices; the pressure reactivity index (PRx), the pulse amplitude index (PAx), and the RAC index. For each index, % times spent with cerebral perfusion pressure (CPP) above and below its CPPopt and upper and lower limits of reactivity were calculated. Patients were dichotomized based on improvement in Glasgow Outcome Scale-Extended (GOSE) scores into Improved vs. Not Improved between 1 and 3 months, 3 and 6 months, and 1- and 6-month post-TBI. Logistic regression analyses were then conducted, adjusting for the International Mission for Prognosis and Analysis of Clinical Trials (IMPACT) variables., Results: This study included a total of 103 patients from the Winnipeg Acute TBI Database. Through Mann-Whitney U testing and logistic regression analysis, it was found that % time spent with CPP below CPPopt was associated with failure to improve in outcome, while % time spent with CPP above CPPopt was generally associated with improvement in outcome., Conclusions: Our study supports the existing narrative that time spent with CPP below CPPopt results in poorer outcomes. However, it also suggests that time spent above CPPopt may not be associated with worse outcomes and is possibly even associated with improvement in outcome., (© 2023. The Author(s).)

Brain tissue oxygen tension (PbtO 2 ) has emerged as a cerebral monitoring modality following traumatic brain injury (TBI). Near-infrared spectroscopy (NIRS)-based regional cerebral oxygen saturation (rSO 2 ) can non-invasively examine cerebral oxygen content and has the potential for high spatial resolution. Past studies examining the relationship between PbtO 2 and NIRS-based parameters have had conflicting results with varying degrees of correlation. Understanding this relationship will help guide multimodal monitoring practices and impact patient care. The aim of this study is to examine the relationship between PbtO 2 and rSO 2 in a cohort of TBI patients by leveraging contemporary statistical methods. A multi-institutional retrospective cohort study of prospectively collected data was performed. Moderate-to-severe adult TBI patients were included with concurrent rSO 2 and PbtO 2 monitoring during their stay in the intensive care unit (ICU). The high-resolution data were analyzed utilizing time series techniques to examine signal stationarity as well as the cross-correlation relationship between the change in PbtO 2 and the change in rSO 2 signals. Finally, modeling of the change in PbtO 2 by the change in rSO 2 was attempted utilizing linear methods that account for the autocorrelative nature of the data signals. A total of 20 subjects were included in the study. Cross-correlative analysis found that changes in PbtO 2 were most significantly correlated with changes in rSO 2 one minute earlier. Through mixed-effects and time series modeling of parameters, changes in rSO 2 were found to often have a statistically significant linear relationship with changes in PbtO 2 that occurred a minute later. However, changes in rSO 2 were inadequate to predict changes in PbtO 2 . In this study, changes in PbtO 2 were found to correlate most with changes in rSO 2 approximately one minute earlier. While changes in rSO 2 were found to contain information about future changes in PbtO 2 , they were not found to adequately model them. This strengthens the body of literature indicating that NIRS-based rSO 2 is not an adequate substitute for PbtO 2 in the management of TBI.

Background: Cerebrovascular reactivity has been identified as a key contributor to secondary injury following traumatic brain injury (TBI). Prevalent intracranial pressure (ICP) based indices of cerebrovascular reactivity are limited by their invasive nature and poor spatial resolution. Fortunately, interest has been building around near infrared spectroscopy (NIRS) based measures of cerebrovascular reactivity that utilize regional cerebral oxygen saturation (rSO 2 ) as a surrogate for pulsatile cerebral blood volume (CBV). In this study, the relationship between ICP- and rSO 2 -based indices of cerebrovascular reactivity, in a cohort of critically ill TBI patients, is explored using classical machine learning clustering techniques and multivariate time-series analysis., Methods: High-resolution physiologic data were collected in a cohort of adult moderate to severe TBI patients at a single quaternary care site. From this data both ICP- and rSO 2 -based indices of cerebrovascular reactivity were derived. Utilizing agglomerative hierarchical clustering and principal component analysis, the relationship between these indices in higher dimensional physiologic space was examined. Additionally, using vector autoregressive modeling, the response of change in ICP and rSO 2 (ΔICP and ΔrSO 2 , respectively) to an impulse in change in arterial blood pressure (ΔABP) was also examined for similarities., Results: A total of 83 patients with 428,775 min of unique and complete physiologic data were obtained. Through agglomerative hierarchical clustering and principal component analysis, there was higher order clustering between rSO 2 - and ICP-based indices, separate from other physiologic parameters. Additionally, modeled responses of ΔICP and ΔrSO 2 to impulses in ΔABP were similar, indicating that ΔrSO 2 may be a valid surrogate for pulsatile CBV., Conclusions: rSO 2 - and ICP-based indices of cerebrovascular reactivity relate to one another in higher dimensional physiologic space. ΔICP and ΔrSO 2 behave similar in modeled responses to impulses in ΔABP. This work strengthens the body of evidence supporting the similarities between ICP-based and rSO 2 -based indices of cerebrovascular reactivity and opens the door to cerebrovascular reactivity monitoring in settings where invasive ICP monitoring is not feasible., (© 2023. European Society of Intensive Care Medicine and Springer Nature Switzerland AG.)

Since its introduction in the 1960s, intracranial pressure (ICP) monitoring has become an indispensable tool in neurocritical care practice and a key component of the management of moderate/severe traumatic brain injury (TBI). The primary utility of ICP monitoring is to guide therapeutic interventions aimed at maintaining physiological ICP and preventing intracranial hypertension. The rationale for such ICP maintenance is to prevent secondary brain injury arising from brain herniation and inadequate cerebral blood flow. There exists a large body of evidence indicating that elevated ICP is associated with mortality and that aggressive ICP control protocols improve outcomes in severe TBI patients. Therefore, current management guidelines recommend a cerebral perfusion pressure (CPP) target range of 60-70 mm Hg and an ICP threshold of >20 or >22 mm Hg, beyond which therapeutic intervention should be initiated. Though our ability to achieve these thresholds has drastically improved over the past decades, there has been little to no change in the mortality and morbidity associated with moderate-severe TBI. This is a result of the "one treatment fits all" dogma of current guideline-based care that fails to take individual phenotype into account. The way forward in moderate-severe TBI care is through the development of continuously derived individualized ICP thresholds. This narrative review covers the topic of ICP monitoring in TBI care, including historical context/achievements, current monitoring technologies and indications, treatment methods, associations with patient outcome and multi-modal cerebral physiology, present controversies surrounding treatment thresholds, and future perspectives on personalized approaches to ICP-directed therapy., Competing Interests: No competing financial interests exist., (© Kevin Y. Stein et al., 2023; Published by Mary Ann Liebert, Inc.)

Background: The aim of this study is to evaluate the impact of commonly administered sedatives (Propofol, Alfentanil, Fentanyl, and Midazolam) and vasopressor (Dobutamine, Ephedrine, Noradrenaline and Vasopressin) agents on cerebrovascular reactivity in moderate/severe TBI patients. Cerebrovascular reactivity, as a surrogate for cerebral autoregulation was assessed using the long pressure reactivity index (LPRx). We evaluated the data in two phases, first we assessed the minute-by-minute data relationships between different dosing amounts of continuous infusion agents and physiological variables using boxplots, multiple linear regression and ANOVA. Next, we assessed the relationship between continuous/bolus infusion agents and physiological variables, assessing pre-/post- dose of medication change in physiology using a Wilcoxon signed-ranked test. Finally, we evaluated sub-groups of data for each individual dose change per medication, focusing on key physiological thresholds and demographics., Results: Of the 475 patients with an average stay of 10 days resulting in over 3000 days of recorded information 367 (77.3%) were male with a median Glasgow coma score of 7 (4-9). The results of this retrospective observational study confirmed that the infusion of most administered agents do not impact cerebrovascular reactivity, which is confirmed by the multiple linear regression components having p value > 0.05. Incremental dose changes or bolus doses in these medications in general do not lead to significant changes in cerebrovascular reactivity (confirm by Wilcoxon signed-ranked p value > 0.05 for nearly all assessed relationships). Within the sub-group analysis that separated the data based on LPRx pre-dose, a significance between pre-/post-drug change in LPRx was seen, however this may be more of a result from patient state than drug impact., Conclusions: Overall, this study indicates that commonly administered agents with incremental dosing changes have no clinically significant influence on cerebrovascular reactivity in TBI (nor do they impair cerebrovascular reactivity). Though further investigation in a larger and more diverse TBI patient population is required., (© 2023. European Society of Intensive Care Medicine and Springer Nature Switzerland AG.)

Objective:  Cerebral blood vessels maintaining relatively constant cerebral blood flow (CBF) over wide range of systemic arterial blood pressure (ABP) is referred to as cerebral autoregulation (CA). Impairments in CA expose the brain to pressure-passive flow states leading to hypoperfusion and hyperperfusion. Cerebrovascular reactivity (CVR) metrics refer to surrogate metrics of pressure-based CA that evaluate the relationship between slow vasogenic fluctuations in cerebral perfusion pressure/ABP and a surrogate for pulsatile CBF/cerebral blood volume. Approach:  We performed a systematically conducted scoping review of all available human literature examining the association between continuous CVR between more than one brain region/channel using the same CVR index. Main Results:  In all the included 22 articles, only handful of transcranial doppler (TCD) and near-infrared spectroscopy (NIRS) based metrics were calculated for only two brain regions/channels. These metrics found no difference between left and right sides in healthy volunteer, cardiac surgery, and intracranial hemorrhage patient studies. In contrast, significant differences were reported in endarterectomy, and subarachnoid hemorrhage studies, while varying results were found regarding regional disparity in stroke, traumatic brain injury, and multiple population studies. Significance:  Further research is required to evaluate regional disparity using NIRS-based indices and to understand if NIRS-based indices provide better regional disparity information than TCD-based indices., (Creative Commons Attribution license.)

Background: Current moderate/severe traumatic brain injury (TBI) guidelines suggest the use of an intracranial pressure (ICP) treatment threshold of 20 mmHg or 22 mmHg. Over the past decade, the use of various cerebral physiology monitoring devices has been incorporated into neurocritical care practice and termed "multimodal monitoring." Such modalities include those that monitor systemic hemodynamics, systemic and brain oxygenation, cerebral blood flow (CBF), cerebral autoregulation, electrophysiology, and cerebral metabolism. Given that the relationship between ICP and outcomes is not yet entirely understood, a comprehensive review of the literature on the associations between ICP thresholds and multimodal monitoring is still needed., Methods: We conducted a scoping review of the literature for studies that present an objective statistical association between ICP above/below threshold and any multimodal monitoring variable. MEDLINE, BIOSIS, Cochrane library, EMBASE, Global Health, and SCOPUS were searched from inception to July 2022 for relevant articles. Full-length, peer-reviewed, original works with a sample size of ≥50 moderate-severe TBI patients were included in this study., Results: A total of 13 articles were deemed eligible for final inclusion. The included articles were significantly heterogenous in terms of their designs, demographics, and results, making it difficult to draw any definitive conclusions. No literature describing the association between guideline-based ICP thresholds and measures of brain electrophysiology, cerebral metabolism, or direct metrics of CBF was found., Conclusion: There is currently little literature that presents objective statistical associations between ICP thresholds and multimodal monitoring physiology. However, overall, the literature indicates that having ICP above guideline based thresholds is associated with increased blood pressure, increased cardiac decoupling, reduced parenchymal brain oxygen tension, and impaired cerebral autoregulation, with no association with CBF velocity within the therapeutic range of ICP. There was insufficient literature to comment on other multimodal monitoring measures., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

To optimally assess oscillatory phenomena within physiological variables, spectral domain transforms are used. A discrete Fourier transform (DFT) is one of the most common methods used to attain this spectral change. In traumatic brain injury (TBI), a DFT is used to derive more complicated methods of physiological assessment, particularly that of cerebrovascular reactivity (CVR). However, a practical application of a DFT will introduce various errors that need to be considered. This study will evaluate the pulse amplitude DFT derivation of intracranial pressure (AMP) to highlight how slight differences in DFT methodologies can impact calculations. Utilizing a high-frequency prospectively maintained data set of TBI patients with recorded arterial and intracranial blood pressure, various cerebral physiological aspects of interest were assessed using the DFT windowing methods of rectangular, Hanning, and Chebyshev. These included AMP, CVR indices (including the pressure reactivity and pulse amplitude index), and the optimal cerebral perfusion pressure (with all methods of CVR). The results of the different DFT-derived windowing methods were compared using the Wilcoxon signed-ranked test and histogram plots between individual patients and over the whole 100-patient cohort. The results for this analysis demonstrate that, overall and for grand average values, there were limited differences between the different DFT windowing techniques. However, there were individual patient outliers to whom the different methods resulted in noticeably different overall values. From this information, for derived indices utilizing a DFT in the assessment of AMP, there are limited differences within the resulting calculations for larger aggregates of data. However, when the amplitude of spectrally resolved response is important and needs to be robust in smaller moments in time, it is recommended to use a window that has amplitude accuracy (such as Chebyshev or flat-top)., Competing Interests: No competing financial interests exist., (© Logan Froese et al., 2023; Published by Mary Ann Liebert, Inc.)

The ability of cerebral vessels to maintain a fairly constant cerebral blood flow is referred to as cerebral autoregulation (CA). Using near-infrared spectroscopy (NIRS) paired with arterial blood pressure (ABP) monitoring, continuous CA can be assessed non-invasively. Recent advances in NIRS technology can help improve the understanding of continuously assessed CA in humans with high spatial and temporal resolutions. We describe a study protocol for creating a new wearable and portable imaging system that derives CA maps of the entire brain with high sampling rates at each point. The first objective is to evaluate the CA mapping system's performance during various perturbations using a block-trial design in 50 healthy volunteers. The second objective is to explore the impact of age and sex on regional disparities in CA using static recording and perturbation testing in 200 healthy volunteers. Using entirely non-invasive NIRS and ABP systems, we hope to prove the feasibility of deriving CA maps of the entire brain with high spatial and temporal resolutions. The development of this imaging system could potentially revolutionize the way we monitor brain physiology in humans since it would allow for an entirely non-invasive continuous assessment of regional differences in CA and improve our understanding of the impact of the aging process on cerebral vessel function.

Impaired cerebrovascular reactivity has emerged as an important associate with poor long-term outcome after moderate/severe traumatic brain injury (TBI). However, our understanding of what drives or modulates the degree of impaired cerebrovascular function remains poor. Age and biological sex remain important modifiers of cerebrovascular function in health and disease, yet their impact on cerebrovascular reactivity after TBI remains unclear. The aim of this study was to explore subgroup responses based on age and biological sex on cerebral physiology. Data from 283 TBI patients from the CAnadian High Resolution TBI (CAHR-TBI) Research Collaborative were evaluated. Cerebrovascular reactivity was determined using high-frequency cerebral physiology for the derivation of three intracranial pressure (ICP)-based indices: 1) pressure reactivity index (PRx)-correlation between ICP and mean arterial pressure (MAP); 2) pulse amplitude index (PAx)-correlation between pulse amplitude of ICP (AMP) and MAP; and 3) RAC-correlation between AMP and cerebral perfusion pressure (CPP). Insult burden (% time above clinically defined thresholds) were calculated for these indices. These cerebral physiology indices were studied for their relationship with age via linear regression, age trichotomization (< 40, 40 - 60, > 60), and decades of age (< 30, 30-39, 40-49, 50-59, 60-69, > 69) schemes. Similarly, differences based on biological sex were assessed. A statistically significant positive linear correlation was found between PAx, RAC, and age. In corollary, a statistically significant relationship was found between increasing age on trichotomized and decades of age analysis with PAx and RAC measures. PRx failed to demonstrate such relationships to advancing age. There was no clear difference in cerebrovascular reactivity profiles between biological sex categories. These findings suggest that AMP-based cerebrovascular reactivity indices may be better positioned to detect impairment in TBI patients with advancing age. Further investigation into the utility of PAx and RAC is required, as they may prove useful for certain subgroups of patients.

Background: Although vasopressor and sedative agents are commonly used within the intensive care unit to mediate systemic and cerebral physiology, the full impact such agents have on cerebrovascular reactivity remains unclear. Using a prospectively maintained database of high-resolution critical care and physiology, the time-series relationship between vasopressor/sedative administration, and cerebrovascular reactivity was interrogated. Cerebrovascular reactivity was assessed through intracranial pressure and near infrared spectroscopy measures. Using these derived measures, the relationship between hourly dose of medication and hourly index values could be evaluated. The individual medication dose change and their corresponding physiological response was compared. Given the high number of doses of propofol and norepinephrine, a latent profile analysis was used to identify any underlying demographic or variable relationships. Finally, using time-series methodologies of Granger causality and vector impulse response functions, the relationships between the cerebrovascular reactivity derived variables were compared., Results: From this retrospective observational study of 103 TBI patients, the evaluation between the changes in vasopressor or sedative agent dosing and the previously described cerebral physiologies was completed. The assessment of the physiology pre/post infusion agent change resulted in similar overall values (Wilcoxon signed-ranked p value > 0.05). Time series methodologies demonstrated that the basic physiological relationships were identical before and after an infusion agent was changed (Granger causality demonstrated the same directional impact in over 95% of the moments, with response function being graphically identical)., Conclusions: This study suggests that overall, there was a limited association between the changes in vasopressor or sedative agent dosing and the previously described cerebral physiologies including that of cerebrovascular reactivity. Thus, current regimens of administered sedative and vasopressor agents appear to have little to no impact on cerebrovascular reactivity in TBI., (© 2023. The Author(s).)

Within traumatic brain injury (TBI) care, there is growing interest in pathophysiological markers as surrogates of disease severity, which may be used to improve and individualize care. Of these, assessment of cerebrovascular reactivity (CVR) has been extensively studied given that it is a consistent, independent factor associated with mortality and functional outcome. However, to date, the literature supports little-to-no impact of current guideline-supported therapeutic interventions on continuously measured CVR. Previous work in this area has suffered from a lack of validation studies, given the rarity of time-matched high-frequency cerebral physiology with serially recorded therapeutic interventions; thus, we undertook a validation study. Utilizing the Winnipeg Acute TBI database, we evaluated the association between daily treatment intensity levels, as measured through the therapeutic intensity level (TIL) scoring system, and continuous multi-modal-derived CVR measures. CVR measures included the intracranial pressure (ICP)-derived pressure reactivity index, pulse amplitude index, and RAC index (a correlation between the pulse amplitude of ICP and cerebral perfusion pressure), as well as the cerebral autoregulation measure of near-infrared spectroscopy-based cerebral oximetry index. These measures were also derived over a key threshold for each day and were compared to the daily total TIL measure. In summary, we could not observe any overall relationship between TIL and these CVR measures. This validates previous findings and represents only the second such analysis to date. This helps to confirm that CVR appears to remain independent of current therapeutic interventions and is a potential unique physiological target for critical care. Further work into the high-frequency relationship between critical care and CVR is required., Competing Interests: No competing financial interests exist., (© Logan Froese et al., 2023; Published by Mary Ann Liebert, Inc.)

Since the Paris Agreement entered into force, climate neutrality and associated compensation schemes are even more on the agenda of politics and companies. Challenges of existing offsetting schemes include the rather theoretical saving scenario and the limited scope of considered impacts. To address some of these limitations, this paper proposes the Circular Ecosystem Compensation (CEC) approach based on monetization of LCA results and Ecosystem Valuation. CEC consists of six steps: i) carrying out a life cycle assessment, ii) reducing the environmental impacts, iii) determining environmental costs applying monetization methods, iv) deriving the environmental value based on restoration costs methods, v) implementing the ecological restoration of ecosystems and vi) monitoring of the renaturation measures. Thus, CEC allows to offset a broad set of environmental impacts beyond climate change (e.g., acidification, eutrophication, land use, water use) in a real ecosystem by renaturation of degraded ecosystems. Environmental burdens and environmental benefits are balanced on a monetary basis, as the renaturation measures are monetized and used to compensate the monetized LCA results, e.g., of a product, organization or individual. In a case study, the implementation of the approach is presented to show the practical implementation of the CEC. The challenges of CEC include the integration of further impact categories, the availability of up-to-date and reliable monetization methods, the asynchrony and time-lag of the compensation from an ecosystem and biodiversity perspective and the proof of cost-efficiency of the renaturation measures. It is further discussed, if CEC can be a step beyond "climate neutrality" towards "environmental neutrality". The proposed approach should be further tested and is intended to foster progress in more comprehensive and robust offsetting of environmental impacts beyond climate change., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Sainbhi, Froese, Gomez, Marquez, Amenta, Batson, Stein and Zeiler.)

Background: Brain tissue oxygen tension (PbtO 2 ) and cerebrovascular pressure reactivity monitoring have emerged as potential modalities to individualize care in moderate and severe traumatic brain injury (TBI). The relationship between these modalities has had limited exploration. The aim of this study was to examine the relationship between PbtO 2 and cerebral perfusion pressure (CPP) and how this relationship is modified by the state of cerebrovascular pressure reactivity., Methods: A retrospective multi-institution cohort study utilizing prospectively collected high-resolution physiologic data from the CAnadian High Resolution-TBI (CAHR-TBI) Research Collaborative database collected between 2011 and 2021 was performed. Included in the study were critically ill TBI patients with intracranial pressure (ICP), arterial blood pressure (ABP), and PbtO 2 monitoring treated in any one of three CAHR-TBI affiliated adult intensive care units (ICU). The outcome of interest was how PbtO 2 and CPP are related over a cohort of TBI patients and how this relationship is modified by the state of cerebrovascular reactivity, as determined using the pressure reactivity index (PRx)., Results: A total of 77 patients met the study inclusion criteria with a total of 377,744 min of physiologic data available for the analysis. PbtO 2 produced a triphasic curve when plotted against CPP like previous population-based plots of cerebral blood flow (CBF) versus CPP. The triphasic curve included a plateau region flanked by regions of relative ischemia (hypoxia) and hyperemia (hyperoxia). The plateau region shortened when cerebrovascular pressure reactivity was disrupted compared to when it was intact., Conclusions: In this exploratory analysis of a multi-institution high-resolution physiology TBI database, PbtO 2 seems to have a triphasic relationship with CPP, over the entire cohort. The CPP range over which the plateau exists is modified by the state of cerebrovascular reactivity. This indicates that in critically ill TBI patients admitted to ICU, PbtO 2 may be reflective of CBF., (© 2022. The Author(s).)

Background: Impaired cerebrovascular reactivity following moderate/severe traumatic brain injury (TBI) has emerged as a key potential driver of morbidity and mortality. However, the major contributions to the literature so far have been solely focused on single point measures of long-term outcome. Therefore, it remains unknown whether cerebrovascular reactivity impairment, during the acute phase of TBI, is associated with failure to improve in outcome across time., Methods: Cerebrovascular reactivity was measured using three intracranial pressure-based surrogate metrics. For each patient, % time spent above various literature-defined thresholds was calculated. Patients were dichotomized based on outcome transition into Improved vs Not Improved between 1 and 3 months, 3 and 6 months, and 1 and 6 months, based on the Glasgow Outcome Scale-Extended (GOSE). Univariate and multivariable logistic regression analyses were performed, adjusting for the International Mission for Prognosis and Analysis of Clinical Trials (IMPACT) variables., Results: Seventy-eight patients from the Winnipeg Acute TBI Database were included in this study. On univariate logistic regression analysis, higher % time with cerebrovascular reactivity metrics above clinically defined thresholds was associated with a lack of clinical improvement between 1 and 3 months and 1 and 6 months post injury (p < 0.05). These relationships held true on multivariable logistic regression analysis., Conclusion: Our study demonstrates that impaired cerebrovascular reactivity, during the acute phase of TBI, is associated with failure to improve clinically over time. These preliminary findings highlight the significance that cerebrovascular reactivity monitoring carries in outcome recovery association in moderate/severe TBI., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Although e-learning has become an important feature to promote learning experience, still little is known about the readiness of adult learners for e-learning in continuing vocational education. By exploring perceived challenges and benefits, it was our aim to identify dimensions that define e-learning readiness. Therefore, we conducted a study design with qualitative and quantitative components. It consisted of both, semi-structured interviews, as well as an online survey regarding biography, personality, learning behavior, and general attitudes toward e-learning. The continuing vocational education course that we were investigating comes from the field of project management. The learner group was heterogeneous regarding their biographical and occupational background. Our results suggest several dimensions of e-learning readiness which are namely: motivation, learning strategies/regulation, attitudes toward learning, and personality-associated aspects as well as digital literacy. These findings are in line with previous research to only some extent, but reveal the necessity to redefine single dimensions of e-learning readiness to develop an inventory that is generalizable for different adult learner groups. Based on these assumptions a new measure for e-learning readiness needs to be proposed in future research as a next step., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Loock, Fleischer, Scheunemann, Froese, Teich and Wirth.)

Background: Impaired cerebral autoregulation has been linked with worse outcomes, with literature suggesting that current therapy guidelines fail to significantly impact cerebrovascular reactivity. The cerebral oximetry index (COx&#95;a) is a surrogate measure of cerebrovascular reactivity which can in theory be obtained non-invasively using regional brain tissue oxygen saturation and arterial blood pressure. The goal of this study was to assess the relationship between objectively measured depth of sedation through BIS and autoregulatory capacity measured through COx&#95;a., Methods: In a prospectively maintained observational study, we collected continuous regional brain tissue oxygen saturation, intracranial pressure, arterial blood pressure and BIS in traumatic brain injury patients. COx&#95;a was obtained using the Pearson's correlation between regional brain tissue oxygen saturation and arterial blood pressure and ranges from - 1 to 1 with higher values indicating impairment of cerebrovascular reactivity. Using BIS values and COx&#95;a, a curve-fitting method was applied to determine the minimum value for the COx&#95;a. The associated BIS value with the minimum COx&#95;a is called BISopt. This BISopt was both visually and algorithmically determined, which were compared and assessed over the whole dataset., Results: Of the 42 patients, we observed that most had a parabolic relationship between BIS and COx&#95;a. This suggests a potential "optimal" depth of sedation where COx&#95;a is the most intact. Furthermore, when comparing the BISopt algorithm with visual inspection of BISopt, we obtained similar results. Finally, BISopt % yield (determined algorithmically) appeared to be independent from any individual sedative or vasopressor agent, and there was agreement between BISopt found with COx&#95;a and the pressure reactivity index (another surrogate for cerebrovascular reactivity)., Conclusions: This study suggests that COx&#95;a is capable of detecting disruption in cerebrovascular reactivity which occurs with over-/under-sedation, utilizing a non-invasive measure of determination and assessment. This technique may carry implications for tailoring sedation in patients, focusing on individualized neuroprotection., (© 2022. The Author(s).)

The process of cerebral vessels regulating constant cerebral blood flow over a wide range of systemic arterial pressures is termed cerebral autoregulation (CA). Static and dynamic autoregulation are two types of CA measurement techniques, with the main difference between these measures relating to the time scale used. Static autoregulation looks at the long-term change in blood pressures, while dynamic autoregulation looks at the immediate change. Techniques that provide regularly updating measures are referred to as continuous, whereas intermittent techniques take a single at point in time. However, a technique being continuous or intermittent is not implied by if the technique measures autoregulation statically or dynamically. This narrative review outlines technical aspects of non-invasive and minimally-invasive modalities along with providing details on the non-invasive and minimally-invasive measurement techniques used for CA assessment. These non-invasive techniques include neuroimaging methods, transcranial Doppler, and near-infrared spectroscopy while the minimally-invasive techniques include positron emission tomography along with magnetic resonance imaging and radiography methods. Further, the advantages and limitations are discussed along with how these methods are used to assess CA. At the end, the clinical considerations regarding these various techniques are highlighted., Competing Interests: DC is affiliated with the Pan Am Clinic Foundation which receives general education and research support from ConMed Linvatec, Ossur, Zimmer Biomet, and Arthrex. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Sainbhi, Gomez, Froese, Slack, Batson, Stein, Cordingley, Alizadeh and Zeiler.)

Literature pertaining to traumatic brain injury care involves the mediation and control of secondary brain injury mechanisms, chief among these is cerebral autoregulation. Cerebral autoregulation is frequently assessed through surrogate measures of cerebrovascular reactivity. An important aspect to acknowledge when calculating cerebrovascular reactivity indices is the linearity within two-parent bio-signals or variables. We highlighted the concept of linearity in raw parent bio-signals used for the calculation of the cerebrovascular reactivity index and what potential implications linearity carries for index derivation. Key of which is that the initial differencing or location of the pressure probes does not influence linear methods of cerebral reactivity calculations so long as the slow-wave vasogenic changes are being recorded., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Froese, Gomez, Sainbhi, Slack and Zeiler.)

Background: We have sought to develop methodology for deriving optimal bispectral index (BIS) values (BISopt) for patients with moderate/severe traumatic brain injury, using continuous monitoring of cerebrovascular reactivity and bispectral electroencephalography., Methods: Arterial blood pressure, intracranial pressure, and BIS (a bilateral measure that is associated with sedation state) were continuously recorded. The pressure reactivity index, optimal cerebral perfusion pressure (CPPopt), and BISopt were calculated. Using BIS values and the pressure reactivity index, a curve fitting method was applied to determine the minimum value for the pressure reactivity index thus giving the BISopt., Results and Conclusions: Identification of BISopt was possible in all of the patients, with both visual inspection of data and using our method of BISopt determination, demonstrating a similarity of median values of 44.62 (35.03-59.98) versus 48 (39.75-57.50) ( p = 0.1949). Furthermore, our method outperformed common CPPopt curve fitting methods applied to BISopt with improved percent (%) yields on both the left side 52.1% (36.3-72.4%) versus 31.2% (23.0-48.9%) ( p < 0.0001) and the right side 54.1% (35.95-75.9%) versus 33.5% (12.5-47.9%) ( p < 0.0001). The BIS values and BISopt were compared with cerebral perfusion pressure, mean arterial pressure, and CPPopt. The results indicated that BISopt's impact on pressure reactivity was distinct from CPPopt, cerebral perfusion pressure, or mean arterial pressure. Real-time BISopt can be derived from continuous physiologic monitoring of patients with moderate/severe traumatic brain injury. This BISopt value appears to be unassociated with arterial blood pressure or CPPopt, supporting its role as a novel physiologic metric for evaluating cerebral autoregulation. BISopt management to optimize cerebrovascular pressure reactivity should be the subject of future studies in moderate/severe traumatic brain injury., Competing Interests: Mr. Froese is supported through the University of Manitoba (UofM)—Department of Surgery Geographical Full Time (GFT) Research Grant and the UofM Office of Research Services—University Research Grant Program. Mr. Stein is supported through the Manitoba Medical Services Foundation (MMSF)—Richard Hoeschen Memorial Award. Dr. Batson is supported through the Centre on Aging at the UofM. Dr. Mendelson is supported by the UofM Department of Internal Medicine New Investigator Grant. Dr. Zeiler receives research support from the Manitoba Public Insurance Neuroscience/Traumatic Brain Injury Research Endowment, the Health Sciences Centre Foundation Winnipeg, the U.S. National Institutes of Health through the National Institute of Neurologic Disorders and Stroke (Grant Number: R03NS114335-01), the Canada Foundation for Innovation (Project Number: 38583), Research Manitoba (Grant Number: 3906), the UofM Vice President Research and International Research Investment Fund, the UofM Centre on Aging, and the UofM Rudy Falk Clinician-Scientist Professorship. Dr. Gomez is supported through the UofM Clinician Investigator Program, the R. Samuel McLaughlin Research Fellowship, the MMSF Research and Education Fellowship Award, and the UofM Dean’s Fellowship Fund Award. Mr. Sainbhi is supported through the UofM—Department of Surgery GFT Research Grant and the UofM Graduate Student Association Award. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2022 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)