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Deranged cerebral autoregulation (CA) is associated with worse outcome in adult brain injury. Strategies for monitoring CA and maintaining the brain at its 'best CA status' have been implemented, however, this approach has not yet developed for the paediatric population. This scoping review aims to find up-to-date evidence on CA assessment in children and neonates with a view to identify patient categories in which CA has been measured so far, CA monitoring methods and its relationship with clinical outcome if any. A literature search was conducted for studies published within 31st December 2022 in 3 bibliographic databases. Out of 494 papers screened, this review includes 135 studies. Our literature search reveals evidence for CA measurement in the paediatric population across different diagnostic categories and age groups. The techniques adopted, indices and thresholds used to assess and define CA are heterogeneous. We discuss the relevance of available evidence for CA assessment in the paediatric population. However, due to small number of studies and heterogeneity of methods used, there is no conclusive evidence to support universal adoption of CA monitoring, technique, and methodology. This calls for further work to understand the clinical impact of CA monitoring in paediatric and neonatal intensive care., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Peter Smielewski and Marek Czosnyka receive part of the licensing fees for ICM+ software, licensed by Cambridge Enterprise Ltd, University of Cambridge, Cambridge.

Objective: Cerebrovascular autoregulation is defined as the capacity of cerebral blood vessels to maintain stable cerebral blood flow despite changing blood pressure. It is assessed using the pressure reactivity index (the correlation coefficient between mean arterial blood pressure and intracranial pressure). The objective of this scoping review is to describe the existing evidence concerning the association of EEG and cerebrovascular autoregulation in order to identify key concepts and detect gaps in the current knowledge., Methods: Embase, MEDLINE, SCOPUS, and Web of Science were searched considering articles between their inception up to September 2023. Inclusion criteria were human (paediatric and adult) and animal studies describing correlations between continuous EEG and cerebrovascular autoregulation assessments., Results: Ten studies describing 481 human subjects (67% adult, 59% critically ill) were identified. Seven studies assessed qualitative (e.g. seizures, epileptiform potentials) and five evaluated quantitative (e.g. bispectral index, alpha-delta ratio) EEG metrics. Cerebrovascular autoregulation was evaluated based on intracranial pressure, transcranial Doppler, or near infrared spectroscopy. Specific combinations of cerebrovascular autoregulation and EEG metrics were evaluated by a maximum of two studies. Seizures, highly malignant patterns or burst suppression, alpha peak frequency, and bispectral index were associated with cerebrovascular autoregulation. The other metrics showed either no or inconsistent associations., Conclusion: There is a paucity of studies evaluating the link between EEG and cerebrovascular autoregulation. The studies identified included a variety of EEG and cerebrovascular autoregulation acquisition methods, age groups, and diseases allowing for few overarching conclusions. However, the preliminary evidence for the presence of an association between EEG metrics and cerebrovascular autoregulation prompts further in-depth investigations., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objectives: The first aim was to investigate the combined effect of insult intensity and duration of the pressure reactivity index (PRx) and deviation from the autoregulatory cerebral perfusion pressure target (∆CPPopt = actual CPP - optimal CPP [CPPopt]) on outcome in traumatic brain injury. The second aim was to determine if PRx influenced the association between intracranial pressure (ICP), CPP, and ∆CPPopt with outcome., Design: Observational cohort study., Setting: Neurocritical care unit, Cambridge, United Kingdom., Patients: Five hundred fifty-three traumatic brain injury patients with ICP and arterial blood pressure monitoring and 6-month outcome data (Glasgow Outcome Scale [GOS])., Intervention: None., Measurements and Main Results: The insult intensity (mm Hg or PRx coefficient) and duration (minutes) of ICP, PRx, CPP, and ∆CPPopt were correlated with GOS and visualized in heatmaps. In these plots, there was a transition from favorable to unfavorable outcome when PRx remained positive for 30 minutes and this was also the case for shorter durations when the intensity was higher. In a similar plot of ∆CPPopt, there was a gradual transition from favorable to unfavorable outcome when ∆CPPopt went below -5 mm Hg for 30-minute episodes of time and for shorter durations for more negative ∆CPPopt. Furthermore, the percentage of monitoring time with certain combinations of PRx with ICP, CPP, and ∆CPPopt were correlated with GOS and visualized in heatmaps. In the combined PRx/ICP heatmap, ICP above 20 mm Hg together with PRx above 0 correlated with unfavorable outcome. In a PRx/CPP heatmap, CPP below 70 mm Hg together with PRx above 0.2-0.4 correlated with unfavorable outcome. In the PRx-/∆CPPopt heatmap, ∆CPPopt below 0 together with PRx above 0.2-0.4 correlated with unfavorable outcome., Conclusions: Higher intensities for longer durations of positive PRx and negative ∆CPPopt correlated with worse outcome. Elevated ICP, low CPP, and negative ∆CPPopt were particularly associated with worse outcomes when the cerebral pressure autoregulation was concurrently impaired., Competing Interests: Dr. Begiri received funding from the Medical Research Council (grant MR N013433-1) and the Gates Cambridge Scholarship. Dr. Bögli received funding from the Swiss National Science Foundation (grant 210839). Dr. Helmy’s institution received funding from the Medical Research Council; they received support for article research from the Research Councils UK. Dr. Smielewski receives part of the licensing fees for ICM+ software, licensed by Cambridge Enterprise Ltd, University of Cambridge, Cambridge. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2024 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Background: Optimization of ventilatory settings is challenging for patients in the neurointensive care unit, requiring a balance between precise gas exchange control, lung protection, and managing hemodynamic effects of positive pressure ventilation. Although recruitment maneuvers (RMs) may enhance oxygenation, they could also exert profound undesirable systemic impacts., Methods: The single-center, prospective study investigated the effects of RMs (up-titration of positive end-expiratory pressure) on multimodal neuromonitoring in patients with acute brain injury. Our primary focus was on intracranial pressure and secondarily on cerebral perfusion pressure (CPP) and other neurological parameters: cerebral autoregulation [pressure reactivity index (PRx)] and regional cerebral oxygenation (rSO 2 ). We also assessed blood pressure and right ventricular (RV) function evaluated using tricuspid annular plane systolic excursion. Results are expressed as the difference (Δ) from baseline values obtained after completing the RMs., Results: Thirty-two patients were enrolled in the study. RMs resulted in increased intracranial pressure (Δ = 4.8 mm Hg) and reduced CPP (ΔCPP = -12.8 mm Hg) and mean arterial pressure (difference in mean arterial pressure = -5.2 mm Hg) (all p < 0.001). Cerebral autoregulation worsened (ΔPRx = 0.31 a.u.; p < 0.001). Despite higher systemic oxygenation (difference in partial pressure of O 2  = 4 mm Hg; p = 0.001) and unchanged carbon dioxide levels, rSO 2 marginally decreased (ΔrSO 2  = -0.5%; p = 0.031), with a significant drop in arterial content and increase in the venous content. RV systolic function decreased (difference in tricuspid annular plane systolic excursion = -0.1 cm; p < 0.001) with a tendency toward increased RV basal diameter (p = 0.06). Grouping patients according to ΔCPP or ΔPRx revealed that those with poorer tolerance to RMs had higher CPP (p = 0.040) and a larger RV basal diameter (p = 0.034) at baseline., Conclusions: In patients with acute brain injury, RMs appear to have adverse effects on cerebral hemodynamics. These findings might be partially explained by RM's impact on RV function. Further advanced echocardiography monitoring is required to prove this hypothesis., (© 2024. The Author(s).)

Objective: To investigate whether cerebral autoregulation is impaired after neonatal cardiac surgery and whether changes in autoregulation metrics are associated with different congenital heart defects or the incidence of postoperative neurologic events., Methods: This is a retrospective observational study of neonates undergoing monitoring during the first 72 hours after cardiac surgery. Archived data were processed to calculate the cerebral oximetry index (COx) and derived metrics. Acute neurologic events were identified by an electronic medical record review. The Skillings-Mack test and the Wilcoxon signed-rank test were used to analyze the evolution of autoregulation metrics over time; the Mann-Whitney U test was used for comparison between groups., Results: We included 28 neonates, 7 (25%) with hypoplastic left heart syndrome and 21 (75%) with transposition of the great arteries. Overall, the median percentage of time spent with impaired autoregulation, defined as percentage of time with a COx >0.3, was 31.6% (interquartile range, 21.1%-38.3%). No differences in autoregulation metrics between different cardiac defects subgroups were observed. Seven patients (25%) experienced a postoperative acute neurologic event. Compared to the neonates without an acute neurologic event, those with an acute neurologic event had a higher COx (0.16 vs 0.07; P = .035), a higher percentage of time with a COx >0.3 (39.4% vs 29.2%; P = .017), and a higher percentage of time with a mean arterial pressure below the lower limit of autoregulation (13.3% vs 6.9%; P = .048)., Conclusions: COx monitoring after cardiac surgery allowed for the detection of impaired cerebral autoregulation, which was more frequent in neonates with postoperative acute neurologic events., Competing Interests: Conflict of Interest Statement P.S. reported receiving licensing fees for ICM+ software, licensed by Cambridge Enterprise Ltd, University of Cambridge. A.M. reported serving on an advisory board for Air Liquide for the administration of iNO in cardiac surgery. C.R. reported consulting fees from Masimo. E.B. reported support from the Medical Research Council (Grant MR N013433-1) and the Gates Cambridge Scholarship. G.R.B. has been supported in part by the MacCutcheon Family Foundation (grant No. 44607). The Journal policy requires editors and reviewers to disclose conflicts of interest and to decline handling or reviewing manuscripts for which they may have a conflict of interest. The editors and reviewers of this article have no conflicts of interest., (Copyright © 2023 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Poor postoperative outcomes may be associated with cerebral ischaemia or hyperaemia, caused by episodes of arterial blood pressure (ABP) being outside the range of cerebral autoregulation (CA). Monitoring CA using COx (correlation between slow changes in mean ABP and regional cerebral O 2 saturation-rSO 2 ) could allow to individualise the management of ABP to preserve CA. We aimed to explore a continuous automated assessment of ABP OPT (ABP where CA is best preserved) and ABP at the lower limit of autoregulation (LLA) in elective neurosurgery patients. Retrospective analysis of prospectively collected data of 85 patients [median age 60 (IQR 51-68)] undergoing elective neurosurgery. ABP BASELINE was the mean of 3 pre-operative non-invasive measurements. ABP and rSO 2 waveforms were processed to estimate COx-derived ABP OPT and LLA trend-lines. We assessed: availability (number of patients where ABP OPT /LLA were available); time required to achieve first values; differences between ABP OPT /LLA and ABP. ABP OPT and LLA availability was 86 and 89%. Median (IQR) time to achieve the first value was 97 (80-155) and 93 (78-122) min for ABP OPT and LLA respectively. Median ABP OPT [75 (69-84)] was lower than ABP BASELINE [90 (84-95)] (p < 0.001, Mann-U test). Patients spent 72 (56-86) % of recorded time with ABP above or below ABP OPT  ± 5 mmHg. ABP OPT and ABP time trends and variability were not related to each other within patients. 37.6% of patients had at least 1 hypotensive insult (ABP < LLA) during the monitoring time. It seems possible to assess individualised automated ABP targets during elective neurosurgery., (© 2024. The Author(s).)

Background: A previous retrospective single-centre study suggested that the percentage of time spent with cerebral perfusion pressure (CPP) below the individual lower limit of reactivity (LLR) is associated with mortality in traumatic brain injury (TBI) patients. We aim to validate this in a large multicentre cohort., Methods: Recordings from 171 TBI patients from the high-resolution cohort of the CENTER-TBI study were processed with ICM+ software. We derived LLR as a time trend of CPP at a level for which the pressure reactivity index (PRx) indicates impaired cerebrovascular reactivity with low CPP. The relationship with mortality was assessed with Mann-U test (first 7-day period), Kruskal-Wallis (daily analysis for 7 days), univariate and multivariate logistic regression models. AUCs (CI 95%) were calculated and compared using DeLong's test., Results: Average LLR over the first 7 days was above 60 mmHg in 48% of patients. %time with CPP < LLR could predict mortality (AUC 0.73, p =  < 0.001). This association becomes significant starting from the third day post injury. The relationship was maintained when correcting for IMPACT covariates or for high ICP., Conclusions: Using a multicentre cohort, we confirmed that CPP below LLR was associated with mortality during the first seven days post injury., (© 2023. The Author(s).)

Many transcranial Doppler ultrasonography devices estimate the mean flow velocity (FVm) by using the traditional formula (FVsystolic + 2 × FVdiastolic)/3 instead of a more accurate formula calculating it as the time integral of the current flow velocities divided by the integration period. We retrospectively analyzed flow velocity and intracranial pressure signals containing plateau waves (transient intracranial hypertension), which were collected from 14 patients with a traumatic brain injury. The differences in FVm and its derivative pulsatility index (PI) calculated with the two different methods were determined. We found that during plateau waves, when the intracranial pressure (ICP) rose, the error in FVm and PI increased significantly from the baseline to the plateau (from 4.6 ± 2.4 to 9.8 ± 4.9 cm/s, P < 0.05). Similarly, the error in PI also increased during plateau waves (from 0.11 ± 0.07 to 0.44 ± 0.24, P < 0.005). These effects were most likely due to changes in the pulse waveform during increased ICP, which alter the relationship between systolic, diastolic, and mean flow velocities. If a change in the mean ICP is expected, then calculation of FVm with the traditional formula is not recommended.

Background: The 'optimal' CPP (CPPopt) concept is based on the vascular pressure reactivity index (PRx). The feasibility and effectiveness of CPPopt guided therapy in severe traumatic brain injury (TBI) patients is currently being investigated prospectively in the COGiTATE trial. At the moment there is no clear evidence that certain admission and treatment characteristics are associated with CPPopt availability (yield)., Objective: To test the relation between patients' admission and treatment characteristics and the average CPPopt yield., Methods: Retrospective analysis of 230 patients from the CENTER-TBI high-resolution database with intracranial pressure (ICP) measured using an intraparenchymal probe. CPPopt was calculated using the algorithm set for the COGiTATE study. CPPopt yield was defined as the percentage of CPP monitored time (%) when CPPopt is available. The variables in the statistical model included age, admission Glasgow Coma Scale (GCS), gender, pupil response, hypoxia and hypotension at the scene, Marshall computed tomography (CT) score, decompressive craniectomy, injury severity score score and 24-h therapeutic intensity level (TIL) score., Results: The median CPPopt yield was 80.7% (interquartile range 70.9-87.4%). None of the selected variables showed a significant statistical correlation with the CPPopt yield., Conclusion: In this retrospective multicenter study, none of the selected admission and treatment variables were related to the CPPopt yield.

Background: Dysfunctional cerebral blood flow autoregulation plays a crucial role in the secondary damage after traumatic brain injury. The pressure reactivity index (PRx) can be used to monitor dynamic cerebral blood flow autoregulation indirectly., Objective: To test different versions of the long pressure reactivity index (LPRx), which is based on minute-by-minute data and calculated over extended time windows, and to study their predictive ability and examine whether "long" and "short" pressure reactivity indices could improve predictive power., Methods: PRx and 3 versions of the LPRx calculated over 20-, 60-, and 240-min time windows were assessed in relation to outcome at 6 mo in 855 patients with traumatic brain injury. Predictive power and discriminative ability of indices were evaluated using area under the operator curves and determination of critical thresholds. PRx and LPR indices were combined to evaluate whether LPR indices could improve outcome prediction by adding information about static components of autoregulation., Results: Correlation of each LPRx with the PRx decreased with increased time windows. LPR indices performed successively worse in their predictive and discriminative ability from 20-min to 240-min time frames. PRx had a significantly higher predictive ability compared to each LPRx. Combining LPRx and PRx did not lead to an improvement of predictive power compared to the PRx alone., Conclusion: The critical threshold and predictive value of the PRx for unfavorable outcome and mortality have been confirmed in one of the largest so far published patient cohorts. LPRx performed significantly worse, and its discriminative and predictive abilities decreased with an increasing calculation window., (Copyright © 2020 by the Congress of Neurological Surgeons.)

Pressure reactivity index (PRx) and brain tissue oxygen (PbtO 2 ) are associated with outcome in traumatic brain injury (TBI). This study explores the relationship between PRx and PbtO 2 in adult moderate/severe TBI. Using the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) high resolution intensive care unit (ICU) sub-study cohort, we evaluated those patients with archived high-frequency digital intraparenchymal intracranial pressure (ICP) and PbtO 2 monitoring data of, a minimum of 6 h in duration, and the presence of a 6 month Glasgow Outcome Scale -Extended (GOSE) score. Digital physiological signals were processed for ICP, PbtO 2 , and PRx, with the % time above/below defined thresholds determined. The duration of ICP, PbtO 2 , and PRx derangements was characterized. Associations with dichotomized 6-month GOSE (alive/dead, and favorable/unfavorable outcome; ≤ 4 = unfavorable), were assessed. A total of 43 patients were included. Severely impaired cerebrovascular reactivity was seen during elevated ICP and low PbtO 2 episodes. However, most of the acute ICU physiological derangements were impaired cerebrovascular reactivity, not ICP elevations or low PbtO 2 episodes. Low PbtO 2 without PRx impairment was rarely seen. % time spent above PRx threshold was associated with mortality at 6 months for thresholds of 0 (area under the curve [AUC] 0.734, p  = 0.003), > +0.25 (AUC 0.747, p  = 0.002) and > +0.35 (AUC 0.745, p  = 0.002). Similar relationships were not seen for % time with ICP >20 mm Hg, and PbtO 2 < 20 mm Hg in this cohort. Extreme impairment in cerebrovascular reactivity is seen during concurrent episodes of elevated ICP and low PbtO 2 . However, the majority of the deranged cerebral physiology seen during the acute ICU phase is impairment in cerebrovascular reactivity, with most impairment occurring in the presence of normal PbtO 2 levels. Measures of cerebrovascular reactivity appear to display the most consistent associations with global outcome in TBI, compared with ICP and PbtO 2 .

Recent single-center retrospective analysis displayed the association between admission computed tomography (CT) markers of diffuse intracranial injury and worse cerebrovascular reactivity. The goal of this study was to further explore these associations using the prospective multi-center Collaborative European Neurotrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) high-resolution intensive care unit (HR ICU) data set. Using the CENTER-TBI HR ICU sub-study cohort, we evaluated those patients with both archived high-frequency digital physiology (100 Hz or higher) and the presence of a digital admission CT scan. Physiological signals were processed for pressure reactivity index (PRx) and both the percent (%) time above defined PRx thresholds and mean hourly dose above threshold. Admission CT injury scores were obtained from the database. Quantitative contusion, edema, intraventricular hemorrhage (IVH), and extra-axial lesion volumes were obtained via semi-automated segmentation. Comparison between admission CT characteristics and PRx metrics was conducted using Mann-U, Jonckheere-Terpstra testing, with a combination of univariate linear and logistic regression techniques. A total of 165 patients were included. Cisternal compression and high admission Rotterdam and Helsinki CT scores, and Marshall CT diffuse injury sub-scores were associated with increased percent (%) time and hourly dose above PRx threshold of 0, +0.25, and +0.35 ( p  < 0.02 for all). Logistic regression analysis displayed an association between deep peri-contusional edema and mean PRx above a threshold of +0.25. These results suggest that diffuse injury patterns, consistent with acceleration/deceleration forces, are associated with impaired cerebrovascular reactivity. Diffuse admission intracranial injury patterns appear to be consistently associated with impaired cerebrovascular reactivity, as measured through PRx. This is in keeping with the previous single-center retrospective literature on the topic. This study provides multi-center validation for those results, and provides preliminary data to support potential risk stratification for impaired cerebrovascular reactivity based on injury pattern.

Background: After traumatic brain injury (TBI), brain tissue can be further damaged when cerebral autoregulation is impaired. Managing cerebral perfusion pressure (CPP) according to computed "optimal CPP" values based on cerebrovascular reactivity indices might contribute to preventing such secondary injuries. In this study, we examined the discriminative value of a low-resolution long pressure reactivity index (LPRx) and its derived "optimal CPP" in comparison to the well-established high-resolution pressure reactivity index (PRx)., Methods: Using the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study dataset, the association of LPRx (correlation between 1-min averages of intracranial pressure and arterial blood pressure over a moving time frame of 20 min) and PRx (correlation between 10-s averages of intracranial pressure and arterial blood pressure over a moving time frame of 5 min) to outcome was assessed and compared using univariate and multivariate regression analysis. "Optimal CPP" values were calculated using a multi-window algorithm that was based on either LPRx or PRx, and their discriminative ability was compared., Results: LPRx and PRx were both significant predictors of mortality in univariate and multivariate regression analysis, but PRx displayed a higher discriminative ability. Similarly, deviations of actual CPP from "optimal CPP" values calculated from each index were significantly associated with outcome in univariate and multivariate analysis. "Optimal CPP" based on PRx, however, trended towards more precise predictions., Conclusions: LPRx and its derived "optimal CPP" which are based on low-resolution data were significantly associated with outcome after TBI. However, they did not reach the discriminative ability of the high-resolution PRx and its derived "optimal CPP." Nevertheless, LPRx might still be an interesting tool to assess cerebrovascular reactivity in centers without high-resolution signal monitoring., Trial Registration: ClinicalTrials.gov Identifier: NCT02210221. First submitted July 29, 2014. First posted August 6, 2014.

Cerebral autoregulation, as measured using the pressure reactivity index (PRx), has been related to global patient outcome in adult patients with traumatic brain injury (TBI). To date, this has been documented without accounting for standard baseline admission characteristics and intracranial pressure (ICP). We evaluated this association, adjusting for baseline admission characteristics and ICP, in a multi-center, prospective cohort. We derived PRx as the correlation between ICP and mean arterial pressure in prospectively collected multi-center data from the High-Resolution Intensive Care Unit (ICU) cohort of the Collaborative European NeuroTrauma Effectiveness Research in TBI (CENTER-TBI) study. Multi-variable logistic regression models were analyzed to assess the association between global outcome (measured as either mortality or dichotomized Glasgow Outcome Score-Extended [GOSE]) and a range of covariates (IMPACT [International Mission for Prognosis and Analysis of Clinical Trials] Core and computed tomography [CT] variables, ICP, and PRx). Performance of these models in outcome association was compared using area under the receiver operating curve (AUC) and Nagelkerke's pseudo-R 2 . One hundred ninety-three patients had a complete data set for analysis. The addition of percent time above threshold for PRx improved AUC and displayed statistically significant increases in Nagelkerke's pseudo-R 2 over the IMPACT Core and IMPACT Core + CT models for mortality. The addition of PRx monitoring to IMPACT Core ± CT + ICP models accounted for additional variance in mortality, when compared to models with IMPACT Core ± CT + ICP alone. The addition of cerebrovascular reactivity monitoring, through PRx, provides a statistically significant increase in association with mortality at 6 months. Our data suggest that cerebrovascular reactivity monitoring may provide complementary information regarding outcomes in TBI.

Background: In traumatic brain injury (TBI) the patterns of intracranial pressure (ICP) waveforms may reflect pathological processes that ultimately lead to unfavorable outcome. In particular, ICP slow waves (sw) (0.005-0.05 Hz) magnitude and complexity have been shown to have positive association with favorable outcome. Mild-moderate hypocapnia is currently used for short periods to treat critical elevations in ICP. Our goals were to assess changes in the ICP sw activity occurring following sudden onset of mild-moderate hypocapnia and to examine the relationship between changes in ICP sw activity and other physiological variables during the hypocapnic challenge., Methods: ICP, arterial blood pressure (ABP), and bilateral middle cerebral artery blood flow velocity (FV), were prospectively collected in 29 adult severe TBI patients requiring ICP monitoring and mechanical ventilation in whom a minute volume ventilation increase (15-20% increase in respiratory minute volume) was performed as part of a clinical CO 2 -reactivity test. The time series were first treated using FFT filter (pass-band set to 0.005-0.05 Hz). Power spectral density analysis was performed. We calculated the following: mean value, standard deviation, variance and coefficient of variation in the time domain; total power and frequency centroid in the frequency domain; cerebrospinal compliance (Ci) and compensatory reserve index (RAP)., Results: Hypocapnia led to a decrease in power and increase in frequency centroid and entropy of slow waves in ICP and FV (not ABP). In a multiple linear regression model, RAP at the baseline was the strongest predictor for the decrease in the power of ICP slow waves (p < 0.001)., Conclusion: In severe TBI patients, a sudden mild-moderate hypocapnia induces a decrease in mean ICP and FV, but also in slow waves power of both signals. At the same time, it increases their higher frequency content and their morphological complexity. The difference in power of the ICP slow waves between the baseline and the hypocapnia period depends on the baseline cerebrospinal compensatory reserve as measured by RAP.

Introduction: Individualising therapy is an important challenge for intensive care of patients with severe traumatic brain injury (TBI). Targeting a cerebral perfusion pressure (CPP) tailored to optimise cerebrovascular autoregulation has been suggested as an attractive strategy on the basis of a large body of retrospective observational data. The objective of this study is to prospectively assess the feasibility and safety of such a strategy compared with fixed thresholds which is the current standard of care from international consensus guidelines., Methods and Analysis: CPPOpt Guided Therapy: Assessment of Target Effectiveness (COGiTATE) is a prospective, multicentre, non-blinded randomised, controlled trial coordinated from Maastricht University Medical Center, Maastricht (The Netherlands). The other original participating centres are Cambridge University NHS Foundation Trust, Cambridge (UK), and University Hospitals Leuven, Leuven (Belgium). Adult severe TBI patients requiring intracranial pressure monitoring are randomised within the first 24 hours of admission in neurocritical care unit. For the control arm, the CPP target is the Brain Trauma Foundation guidelines target (60-70 mm Hg); for the intervention group an automated CPP target is provided as the CPP at which the patient's cerebrovascular reactivity is best preserved (CPPopt). For a maximum of 5 days, attending clinicians review the CPP target 4-hourly. The main hypothesis of COGiTATE are: (1) in the intervention group the percentage of the monitored time with measured CPP within a range of 5 mm Hg above or below CPPopt will reach 36%; (2) the difference in between groups in daily therapy intensity level score will be lower or equal to 3., Ethics and Dissemination: Ethical approval has been obtained for each participating centre. The results will be presented at international scientific conferences and in peer-reviewed journals., Trial Registration Number: NCT02982122., Competing Interests: Competing interests: PS and MCz receive part of the licensing fees for multimodal brain monitoring software ICM+, licensed by Cambridge Enterprise Ltd, University of Cambridge, UK. There are no other conflicts of interest to declare., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Impaired cerebrovascular reactivity in adult traumatic brain injury (TBI) is known to be associated with poor outcome. However, there has yet to be an analysis of the association between the comprehensively assessed intracranial hypertension therapeutic intensity level (TIL) and cerebrovascular reactivity., Methods: Using the Collaborative European Neuro Trauma Effectiveness Research in TBI (CENTER-TBI) high-resolution intensive care unit (ICU) cohort, we derived pressure reactivity index (PRx) as the moving correlation coefficient between slow-wave in ICP and mean arterial pressure, updated every minute. Mean daily PRx, and daily % time above PRx of 0 were calculated for the first 7 days of injury and ICU stay. This data was linked with the daily TIL-Intermediate scores, including total and individual treatment sub-scores. Daily mean PRx variable values were compared for each TIL treatment score via mean, standard deviation, and the Mann U test (Bonferroni correction for multiple comparisons). General fixed effects and mixed effects models for total TIL versus PRx were created to display the relation between TIL and cerebrovascular reactivity., Results: A total of 249 patients with 1230 ICU days of high frequency physiology matched with daily TIL, were assessed. Total TIL was unrelated to daily PRx. Most TIL sub-scores failed to display a significant relationship with the PRx variables. Mild hyperventilation (p < 0.0001), mild hypothermia (p = 0.0001), high levels of sedation for ICP control (p = 0.0001), and use vasopressors for CPP management (p < 0.0001) were found to be associated with only a modest decrease in mean daily PRx or % time with PRx above 0., Conclusions: Cerebrovascular reactivity remains relatively independent of intracranial hypertension therapeutic intensity, suggesting inadequacy of current TBI therapies in modulating impaired autoregulation. These findings support the need for investigation into the molecular mechanisms involved, or individualized physiologic targets (ICP, CPP, or Co2) in order to treat dysautoregulation actively.