Liberal or Restrictive Transfusion Strategy in Patients with Traumatic Brain Injury.

BACKGROUND: The effect of a liberal transfusion strategy as compared with a restrictive strategy on outcomes in critically ill patients with traumatic brain injury is unclear. METHODS: We randomly assigned adults with moderate or severe traumatic brain injury and anemia to receive transfusion of red cells according to a liberal strategy (transfusions initiated at a hemoglobin level of ≤10 g per deciliter) or a restrictive strategy (transfusions initiated at ≤7 g per deciliter). The primary outcome was an unfavorable outcome as assessed by the score on the Glasgow Outcome Scale-Extended at 6 months, which we categorized with the use of a sliding dichotomy that was based on the prognosis of each patient at baseline. Secondary outcomes included mortality, functional independence, quality of life, and depression at 6 months. RESULTS: A total of 742 patients underwent randomization, with 371 assigned to each group. The analysis of the primary outcome included 722 patients. The median hemoglobin level in the intensive care unit was 10.8 g per deciliter in the group assigned to the liberal strategy and 8.8 g per deciliter in the group assigned to the restrictive strategy. An unfavorable outcome occurred in 249 of 364 patients (68.4%) in the liberal-strategy group and in 263 of 358 (73.5%) in the restrictive-strategy group (adjusted absolute difference, restrictive strategy vs. liberal strategy, 5.4 percentage points; 95% confidence interval, -2.9 to 13.7). Among survivors, a liberal strategy was associated with higher scores on some but not all the scales assessing functional independence and quality of life. No association was observed between the transfusion strategy and mortality or depression. Venous thromboembolic events occurred in 8.4% of the patients in each group, and acute respiratory distress syndrome occurred in 3.3% and 0.8% of patients in the liberal-strategy and restrictive-strategy groups, respectively. CONCLUSIONS: In critically ill patients with traumatic brain injury and anemia, a liberal transfusion strategy did not reduce the risk of an unfavorable neurologic outcome at 6 months. (Funded by the Canadian Institutes of Health Research and others; HEMOTION ClinicalTrials.gov number, NCT03260478.).

Prognostic value of near-infrared spectroscopy regional oxygen saturation and cerebrovascular reactivity index in acute traumatic neural injury: a CAnadian High-Resolution Traumatic Brain Injury (CAHR-TBI) Cohort Study.

BACKGROUND: Near-infrared spectroscopy regional cerebral oxygen saturation (rSO2) 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 rSO2 and rSO2-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 rSO2 and cerebral perfusion pressure) as well as COx_a (using rSO2 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 rSO2 at which outcomes were found to worsen. For both COx and COx_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 rSO2was found to contain no significant prognostic information. However, rSO2-based indices of CVR, COx and COx_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.

Identifying the Cerebral Physiologic Response to Aerobic Exercise Following Concussion: A Scoping Review.

OBJECTIVE: The purpose of this study was to identify the cerebral physiologic response to aerobic exercise in individuals with a symptomatic concussion, highlighting available knowledge and knowledge gaps in the literature. DESIGN: A systematic scoping review was conducted and reported in keeping with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) extension for scoping reviews. A search of EMBASE, MEDLINE, SCOPUS, BIOSIS, and Cochrane libraries was conducted on June 15, 2023 (from database inception). An online systematic/scoping review management system was used to remove duplicates, and the remaining articles were screened for inclusion by 2 researchers. Inclusion criteria required articles to be original research published in peer-reviewed journals. Additionally, studies were required to have an aerobic exercise component, include a measure of cerebral physiology during a bout of aerobic exercise, exclude moderate and/or severe traumatic brain injury (TBI) populations, and be in the English language. Both human and animal studies were included, with participants of any age who were diagnosed with a mild TBI/concussion only (ie, Glasgow Coma Scale score ≥ 13). Studies could be of any design as long as a measure of cerebral physiologic response to a bout of aerobic exercise was included. RESULTS: The search resulted in 1773 articles to be screened and data from 3 eligible studies were extracted. CONCLUSIONS: There are currently too few studies investigating the cerebral physiologic response to aerobic exercise following concussion or mild TBI to draw definitive conclusions. Further research on this topic is necessary since understanding the cerebral physiologic response to aerobic exercise in the concussion and mild TBI populations could assist in optimizing exercise-based treatment prescription and identifying other targeted therapies.

Non-Invasive Estimation of Intracranial Pressure-Derived Cerebrovascular Reactivity Using Near-Infrared Spectroscopy Sensor Technology in Acute Neural Injury: A Time-Series Analysis.

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.

Time-Series Modeling and Forecasting of Cerebral Pressure-Flow Physiology: A Scoping Systematic Review of the Human and Animal Literature.

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.

Optimal bispectral index exists in healthy patients undergoing general anesthesia: A validation study.

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.

Continuous monitoring methods of cerebral compliance and compensatory reserve: a scoping review of human literature.

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.

Near-Infrared Spectroscopy Regional Oxygen Saturation Based Cerebrovascular Reactivity Assessments in Chronic Traumatic Neural Injury versus in Health: A Prospective Cohort Study.

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.

Associations Between Intracranial Pressure Extremes and Continuous Metrics of Cerebrovascular Pressure Reactivity in Acute Traumatic Neural Injury: A Scoping Review.

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.

Multivariate modeling and prediction of cerebral physiology in acute traumatic neural injury: A scoping review.

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.

Microvascular Autoregulation in Skeletal Muscle Using Near-Infrared Spectroscopy and Derivation of Optimal Mean Arterial Pressure in the ICU: Pilot Study and Comparison With Cerebral Near-Infrared Spectroscopy.

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.

Evaluation of Morlet Wavelet Analysis for Artifact Detection in Low-Frequency Commercial Near-Infrared Spectroscopy Systems.

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.