Search

Abstract 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_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_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_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.

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.

Monitoring cerebral oxygenation and metabolism, using a combination of invasive and non-invasive sensors, is vital due to frequent disruptions in hemodynamic regulation across various diseases. These sensors generate continuous high-frequency data streams, including intracranial pressure (ICP) and cerebral perfusion pressure (CPP), providing real-time insights into cerebral function. Analyzing these signals is crucial for understanding complex brain processes, identifying subtle patterns, and detecting anomalies. Computational models play an essential role in linking sensor-derived signals to the underlying physiological state of the brain. Multivariate machine learning models have proven particularly effective in this domain, capturing intricate relationships among multiple variables simultaneously and enabling the accurate modeling of cerebral physiologic signals. These models facilitate the development of advanced diagnostic and prognostic tools, promote patient-specific interventions, and improve therapeutic outcomes. Additionally, machine learning models offer great flexibility, allowing different models to be combined synergistically to address complex challenges in sensor-based data analysis. Ensemble learning techniques, which aggregate predictions from diverse models, further enhance predictive accuracy and robustness. This review explores the use of multivariate machine learning models in cerebral physiology as a whole, with an emphasis on sensor-derived signals related to hemodynamics, cerebral oxygenation, metabolism, and other modalities such as electroencephalography (EEG) and functional near-infrared spectroscopy (fNIRS) where applicable. It will detail the operational principles, mathematical foundations, and clinical implications of these models, providing a deeper understanding of their significance in monitoring cerebral function.

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.

Abstract 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.

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.

Abstract 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 (rSO2) as a surrogate for pulsatile cerebral blood volume (CBV). In this study, the relationship between ICP- and rSO2-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 rSO2-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 rSO2 (ΔICP and ΔrSO2, 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 rSO2- and ICP-based indices, separate from other physiologic parameters. Additionally, modeled responses of ΔICP and ΔrSO2 to impulses in ΔABP were similar, indicating that ΔrSO2 may be a valid surrogate for pulsatile CBV. Conclusions rSO2- and ICP-based indices of cerebrovascular reactivity relate to one another in higher dimensional physiologic space. ΔICP and ΔrSO2 behave similar in modeled responses to impulses in ΔABP. This work strengthens the body of evidence supporting the similarities between ICP-based and rSO2-based indices of cerebrovascular reactivity and opens the door to cerebrovascular reactivity monitoring in settings where invasive ICP monitoring is not feasible.

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.

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).

Abstract 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.

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.

Abstract Background Brain tissue oxygen tension (PbtO2) 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 PbtO2 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 PbtO2 monitoring treated in any one of three CAHR-TBI affiliated adult intensive care units (ICU). The outcome of interest was how PbtO2 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. PbtO2 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, PbtO2 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, PbtO2 may be reflective of CBF.

Near-infrared spectroscopy (NIRS) regional cerebral oxygen saturation (rSO2)-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_a) was not statistically different between males and females or in the dominant and non-dominant hemispheres. In the TBI cohort, COx_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_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.

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.

Abstract 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_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_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_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_a, a curve-fitting method was applied to determine the minimum value for the COx_a. The associated BIS value with the minimum COx_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_a. This suggests a potential “optimal” depth of sedation where COx_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_a and the pressure reactivity index (another surrogate for cerebrovascular reactivity). Conclusions This study suggests that COx_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.

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.

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 (rSO2)-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 rSO2-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 rSO2-based indices of CVR to model ICP-based indices. It was found that rSO2-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 rSO2-based indices of CVR and potential greatly expands the scope of CVR monitoring.

Regional cerebral oxygen saturation (rSO2), 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 rSO2 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 rSO2 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 rSO2 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.

IntroductionAcute traumatic spinal cord injury is routinely managed by surgical decompression and instrumentation of the spine. Guidelines also suggest elevating mean arterial pressure to 85 mmHg to mitigate secondary injury. However, the evidence for these recommendations remains very limited. There is now considerable interest in measuring spinal cord perfusion pressure by monitoring mean arterial pressure and intraspinal pressure. Here, we present our first institutional experience of using a strain gauge pressure transducer monitor to measure intraspinal pressure and subsequent derivation of spinal cord perfusion pressure.Case presentationThe patient presented to medical attention after a fall off of scaffolding. A trauma assessment was completed at a local emergency room. He did not have any motor strength or sensation to the lower extremities. A computed tomography (CT) scan of the thoracolumbar spine confirmed a T12 burst fracture with retropulsion of bone fragments into the spinal canal. He was taken to surgery for urgent decompression of the spinal cord and instrumentation of the spine. A subdural strain gauge pressure monitor was placed at the site of injury through a small dural incision. Mean arterial pressure and intraspinal pressure were then monitored for 5 days after surgery. Spinal cord perfusion pressure was derived. The procedure was performed without complication and the patient underwent rehabilitation for 3 months where he regained some motor and sensory function in his lower extremities.ConclusionThe first North American attempt at insertion of a strain gauge pressure monitor into the subdural space at the site of injury following acute traumatic spinal cord injury was performed successfully and without complication. Spinal cord perfusion pressure was derived successfully using this physiological monitoring. Further research efforts to validate this technique are required.

To date, there has been limited literature exploring the association between age and sex with cerebrovascular reactivity (CVR) in moderate/severe traumatic brain injury (TBI). Given the known link between age, sex, and cerebrovascular function, knowledge of the impacts on continuously assessed CVR is critical for the development of future therapeutics. We conducted a scoping review of the literature for studies that had a direct statistical interrogation of the relationship between age, sex, and continuous intracranial pressure (ICP)-based indices of CVR in moderate/severe TBI. The ICP-based indices researched included: pressure reactivity index (PRx), pulse amplitude index (PAx), and RAC. MEDLINE, BIOSIS, EMBASE, SCOPUS, Global Health, and the Cochrane library were searched from inception to June 2021 for relevant articles. A total of 10 original studies fulfilled our inclusion criteria. Nine of the articles documented a correlation between advanced age and worse CVR, with eight using PRx (2192 total patients), three using PAx (978 total patients), and one using RAC (358 total patients), p?0.05; R ranging from 0.17 to 0.495 for all indices across all studies. Three articles (1256 total patients) displayed a correlation between biological sex and PRx, with females trending towards higher PRx values (p?

Over a wide range of systemic arterial pressures, cerebral blood flow (CBF) is regulated fairly constantly by the cerebral vessels in a process termed cerebral autoregulation (CA), which is depicted by the Lassen autoregulatory curve. After traumatic brain injury (TBI), CA can get impaired and these impairments manifest in changes of the Lassen autoregulatory curve. Continuous surrogate metrics of pressure-based CA, termed cerebrovascular reactivity (CVR) metrics, evaluate the relationship between slow vasogenic fluctuations in a driving pressure for cerebral blood flow, and the most commonly studied and utilized measures are based in the time domain and have been increasingly applied in bedside TBI care and have sparked the investigation of individualized cerebral perfusion pressure targets. However, not all CVR metrics have been validated as true measures of autoregulation in the pre-clinical setting. We reviewed all available pre-clinical animal literature that assessed the association between continuous time-domain metrics of CVR and some aspect of the Lassen autoregulatory curve. All 15 articles found associated the evaluated continuous metrics to the lower limit of autoregulation curve whereas none looked at the upper limit. Most of the evaluated metrics showed the ability to discriminate the lower limit of autoregulation with various methods of perturbation. Further work is required to evaluate the utility of such surrogate measures against the upper limit of autoregulation, while also providing validation to the existing literature supporting specific indices and their ability to discriminate the lower limit.

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

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.

Brain tissue oxygen tension (PbtO2) has emerged as a cerebral monitoring modality following traumatic brain injury (TBI). Near-infrared spectroscopy (NIRS)-based regional cerebral oxygen saturation (rSO2) can non-invasively examine cerebral oxygen content and has the potential for high spatial resolution. Past studies examining the relationship between PbtO2 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 PbtO2 and rSO2 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 rSO2 and PbtO2 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 PbtO2 and the change in rSO2 signals. Finally, modeling of the change in PbtO2 by the change in rSO2 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 PbtO2 were most significantly correlated with changes in rSO2 one minute earlier. Through mixed-effects and time series modeling of parameters, changes in rSO2 were found to often have a statistically significant linear relationship with changes in PbtO2 that occurred a minute later. However, changes in rSO2 were inadequate to predict changes in PbtO2. In this study, changes in PbtO2 were found to correlate most with changes in rSO2 approximately one minute earlier. While changes in rSO2 were found to contain information about future changes in PbtO2, they were not found to adequately model them. This strengthens the body of literature indicating that NIRS-based rSO2 is not an adequate substitute for PbtO2 in the management of TBI.

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 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.

Cerebral blood flow (CBF) is an important physiologic parameter that is vital for proper cerebral function and recovery. Current widely accepted methods of measuring CBF are cumbersome, invasive, or have poor spatial or temporal resolution. Near infrared spectroscopy (NIRS) based measures of cerebrovascular physiology may provide a means of non-invasively, topographically, and continuously measuring CBF. We performed a systematically conducted scoping review of the available literature examining the quantitative relationship between NIRS-based cerebrovascular metrics and CBF. We found that continuous-wave NIRS (CW-NIRS) was the most examined modality with dynamic contrast enhanced NIRS (DCE-NIRS) being the next most common. Fewer studies assessed diffuse correlation spectroscopy (DCS) and frequency resolved NIRS (FR-NIRS). We did not find studies examining the relationship between time-resolved NIRS (TR-NIRS) based metrics and CBF. Studies were most frequently conducted in humans and animal studies mostly utilized large animal models. The identified studies almost exclusively used a Pearson correlation analysis. Much of the literature supported a positive linear relationship between changes in CW-NIRS based metrics, particularly regional cerebral oxygen saturation (rSO2), and changes in CBF. Linear relationships were also identified between other NIRS based modalities and CBF, however, further validation is needed.

The impact of vasopressor and sedative drugs on cerebrovascular reactivity in traumatic brain injury (TBI) remains unclear. The aim of this study was to evaluate the impact of changes of doses of commonly administered sedation (i.e., propofol, fentanyl, and ketamine) and vasopressor agents (i.e., norepinephrine [NE], phenylephrine [PE], and vasopressin[VSP]) on cerebrovascular reactivity and compensatory reserve in patients with moderate/severe TBI. Using the Winnipeg Acute TBI Database, we identified 38 patients with more than 1000 distinct changes of infusion rates and more than 500?h of paired drug infusion/physiology data. Cerebrovascular reactivity was assessed using pressure reactivity index (PRx) and cerebral compensatory reserve was assessed using RAP (the correlation [R] between pulse amplitude of intracranial pressure [ICP; A] and ICP [P]). We evaluated the data in two phases. First, we assessed the relationship between mean hourly dose of medication and its relation to both mean hourly index values, and time spent above a given index threshold. Second, we evaluated time-series data for each individual dose change per medication, assessing for a statistically significant change in PRx and RAP metrics. The results of the analysis confirmed that, overall, the mean hourly dose of sedative (propofol, fentanyl, and ketamine) and vasopressor (NE, PE, and VSP) agents does not impact hourly cerebrovascular reactivity or compensatory reserve measures. Similarly, incremental dose changes in these medications in general do not lead to significant changes in cerebrovascular reactivity or compensatory reserve. For propofol with incremental dose increases, in situations where PRx is intact (i.e., PRx

Intravenous propofol, fentanyl, and midazolam are utilized commonly in critical care for metabolic suppression and anesthesia. The impact of propofol, fentanyl, and midazolam on cerebrovasculature and cerebral blood flow (CBF) is unclear in traumatic brain injury (TBI) and may carry important implications, as care is shifting to focus on cerebrovascular reactivity monitoring/directed therapies. The aim of this study was to perform a scoping review of the literature on the cerebrovascular/CBF effects of propofol, fentanyl, and midazolam in human patients with moderate/severe TBI and animal models with TBI. A search of MEDLINE, BIOSIS, EMBASE, Global Health, SCOPUS, and the Cochrane Library from inception to May 2020 was performed. All articles were included pertaining to the administration of propofol, fentanyl, and midazolam, in which the impact on CBF/cerebral vasculature was recorded. We identified 14 studies: 8 that evaluated propofol, 5 that evaluated fentanyl, and 2 that evaluated midazolam. All studies suffered from significant limitations, including: small sample size, and heterogeneous design and measurement techniques. In general, there was no significant change seen in CBF/cerebrovascular response to administration of propofol, fentanyl, or midazolam during experiments where PCO2 and mean arterial pressure (MAP) were controlled. This review highlights the current knowledge gap surrounding the impact of commonly utilized sedative drugs in TBI care. This work supports the need for dedicated studies, both experimental and human-based, evaluating the impact of these drugs on CBF and cerebrovascular reactivity/response in TBI.

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.

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.

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.

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.

Multimodal monitoring has been gaining traction in the critical care of patients following traumatic brain injury (TBI). Through providing a deeper understanding of the individual patient’s comprehensive physiologic state, or “physiome,” following injury, these methods hold the promise of improving personalized care and advancing precision medicine. One of the modalities being explored in TBI care is near-infrared spectroscopy (NIRS), given it’s non-invasive nature and ability to interrogate microvascular and tissue oxygen metabolism. In this narrative review, we begin by discussing the principles of NIRS technology, including spatially, frequency, and time-resolved variants. Subsequently, the applications of NIRS in various phases of clinical care following TBI are explored. These applications include the pre-hospital, intraoperative, neurocritical care, and outpatient/rehabilitation setting. The utility of NIRS to predict functional outcomes and evaluate dysfunctional cerebrovascular reactivity is also discussed. Finally, future applications and potential advancements in NIRS-based physiologic monitoring of TBI patients are presented, with a description of the potential integration with other omics biomarkers.

Despite changes in guideline-based management of moderate/severe traumatic brain injury (TBI) over the preceding decades, little impact on mortality and morbidity have been seen. This argues against the “one-treatment fits all” approach to such management strategies. With this, some preliminary advances in the area of personalized medicine in TBI care have displayed promising results. However, to continue transitioning toward individually-tailored care, we require integration of complex “-omics” data sets. The past few decades have seen dramatic increases in the volume of complex multi-modal data in moderate and severe TBI care. Such data includes serial high-fidelity multi-modal characterization of the cerebral physiome, serum/cerebrospinal fluid proteomics, admission genetic profiles, and serial advanced neuroimaging modalities. Integrating these complex and serially obtained data sets, with patient baseline demographics, treatment information and clinical outcomes over time, can be a daunting task for the treating clinician. Within this review, we highlight the current status of such multi-modal omics data sets in moderate/severe TBI, current limitations to the utilization of such data, and a potential path forward through employing integrative neuroinformatic approaches, which are applied in other neuropathologies. Such advances are positioned to facilitate the transition to precision prognostication and inform a top-down approach to the development of personalized therapeutics in moderate/severe TBI.

Introduction: As real time data processing is integrated with medical care for traumatic brain injury (TBI) patients, there is a requirement for devices to have digital output. However, there are still many devices that fail to have the required hardware to export real time data into an acceptable digital format or in a continuously updating manner. This is particularly the case for many intravenous pumps and older technological systems. Such accurate and digital real time data integration within TBI care and other fields is critical as we move towards digitizing healthcare information and integrating clinical data streams to improve bedside care. We propose to address this gap in technology by building a system that employs Optical Character Recognition through computer vision, using real time images from a pump monitor to extract the desired real time information.Methods: Using freely available software and readily available technology, we built a script that extracts real time images from a medication pump and then processes them using Optical Character Recognition to create digital text from the image. This text was then transferred to an ICM + real-time monitoring software in parallel with other retrieved physiological data.Results: The prototype that was built works effectively for our device, with source code openly available to interested end-users. However, future work is required for a more universal application of such a system.Conclusion: Advances here can improve medical information collection in the clinical environment, eliminating human error with bedside charting, and aid in data integration for biomedical research where many complex data sets can be seamlessly integrated digitally. Our design demonstrates a simple adaptation of current technology to help with this integration.

Background: Current understanding of the impact that sedative agents have on neurovascular coupling, cerebral blood flow (CBF) and cerebrovascular response remains uncertain. One confounding factor regarding the impact of sedative agents is the depth of sedation, which is often determined at the bedside using clinical examination scoring systems. Such systems do not objectively account for sedation depth at the neurovascular level. As the depth of sedation can impact CBF and cerebral metabolism, the need for objective assessments of sedation depth is key. This is particularly the case in traumatic brain injury (TBI), where emerging literature suggests that cerebrovascular dysfunction dominates the burden of physiological dysfunction. Processed electroencephalogram (EEG) entropy measures are one possible solution to objectively quantify depth of sedation. Such measures are widely employed within anesthesia and are easy to employ at the bedside. However, the association between such EEG measures and cerebrovascular response remains unclear. Thus, to improve our understanding of the relationship between objectively measured depth of sedation and cerebrovascular response, we performed a scoping review of the literature.Methods: A systematically conduced scoping review of the existing literature on objectively measured sedation depth and CBF/cerebrovascular response was performed, search multiple databases from inception to November 2020. All available literature was reviewed to assess the association between objective sedation depth [as measured through processed electroencephalogram (EEG)] and CBF/cerebral autoregulation.Results: A total of 13 articles, 12 on adult humans and 1 on animal models, were identified. Initiation of sedation was found to decrease processed EEG entropy and CBF/cerebrovascular response measures. However, after this initial drop in values there is a wide range of responses in CBF seen. There were limited statistically reproduceable associations between processed EEG and CBF/cerebrovascular response. The literature body remains heterogeneous in both pathological states studied and sedative agent utilized, limiting the strength of conclusions that can be made.Conclusions: Conclusions about sedation depth, neurovascular coupling, CBF, and cerebrovascular response are limited. Much further work is required to outline the impact of sedation on neurovascular coupling.

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.

Dear Editor: We read with great interest the recent publication in the journal by Khan and colleagues, from the University of Cambridge, regarding the application of robotic transcranial Doppler (TCD) for continuous and entirely non-invasive outpatient assessment of cerebrovascular reactivity.1 In the past 25 years, there has been great progress in the development and understanding of continuous cerebrovascular reactivity indices in traumatic brain injury (TBI). The classic continuous index is the pressure reactivity index (PRx), defined by Czosnyka and associates,2 and refers to the moving Pearson correlation coefficient between slow-wave vasogenic fluctuations in intracranial pressure (ICP) and mean arterial pressure (MAP). This metric, and all other similarly derived moving Pearson correlation-based cerebrovascular metrics are bounded functions, ranging from ?1 to +1, with negative values representing ?intact? and positive values ?impaired? cerebrovascular reactivity, respectively. Such metrics, predominantly PRx, do have some experimental literature supporting their ability to discern the lower limit of autoregulation. To date, numerous studies, both retrospective and prospective, from single and multi-center collaboratives, have demonstrated strong links between impaired cerebrovascular reactivity during the acute phase of a patient's intensive care unit (ICU) stay and poor 6-month outcome in moderate and severe TBI.3 Cerebrovascular reactivity measures have even been shown to be independently associated with outcome in such TBI populations, after adjusting for baseline prognostic model features, such as those utilized in the International Mission for Prognosis and Analysis of Clinical Trials (IMPACT) TBI prognostic models.4 However, recent work supports the notion that many of the advances seen in bedside TBI care over the past decades, leading to improved ICP and cerebral perfusion pressure (CPP) targeting, have failed to leave an impact on the rate of impaired cerebrovascular reactivity.5 As such, work is ongoing through multiple multi-center and international collaboratives, evaluating therapeutic avenues for such physiological derangements. With all of the advances seen in bedside ICU assessments of cerebrovascular reactivity in TBI, there is still much work to do. Classically, the continuous assessment of cerebrovascular reactivity in patients with TBI has stopped after their ICU stay. This is related to the need for measurement of ICP, or CPP, for the derivation of such cerebrovascular reactivity indices, as is the case with PRx, where ICP and MAP data have been obtained through invasive means. With advances in data acquisition platforms, such as intensive care monitoring plus (ICM+), and acceptance of non-invasive cerebral physiological monitoring, such as near infrared spectroscopy (NIRS)-based regional cerebral oxygen saturation (rSO2) and TCD, the concept of ?non-invasive? metrics of cerebrovascular reactivity has arisen. Using NIRS-based rSO2 (or other measures, depending on oximeter manufacturer) as a surrogate for pulsatile cerebral blood volume, or TCD-based cerebral blood flow velocity (CBFV) as a surrogate for cerebral blood flow, this continuous non-invasive cerebral physiological data can be married with entirely non-invasive full-waveform arterial blood pressure (ABP) data, to generate non-invasive continuous cerebrovascular reactivity indices. Further, with advances in robotic technology, as referenced in the article, the past limitations of TCD in obtaining high-quality long-duration recordings is becoming less of an issue. Kahn and colleagues describe the first feasibility study regarding the application of robotic TCD-based continuous non-invasive cerebrovascular reactivity in an outpatient setting. They found the technique to be not only feasible for up to 2?h of continuous uninterrupted data collection, but also to be well tolerated by the pilot cohort studied. The authors should be applauded for this advancement in the field of continuous neuromonitoring in the mild TBI population. Such work mirrors that being done using NIRS-based platforms for long-term follow-up of moderate/severe TBI populations.6,7 We look forward to the continued contributions from the Cambridge group regarding this, as their planned study correlating cerebrovascular function, assessed continuously in the clinic using their described setup, and persistent post-traumatic symptomatology, carry significant implications for the future of outpatient TBI assessment.