Search

Cerebral Autoregulation (CA) is an important physiological mechanism stabilizing cerebral blood flow (CBF) in response to changes in cerebral perfusion pressure (CPP). By maintaining an adequate, relatively constant supply of blood flow, CA plays a critical role in brain function. Quantifying CA under different physiological and pathological states is crucial for understanding its implications. This knowledge may serve as a foundation for informed clinical decision-making, particularly in cases where CA may become impaired. The quantification of CA functionality typically involves constructing models that capture the relationship between CPP (or arterial blood pressure) and experimental measures of CBF. Besides describing normal CA function, these models provide a means to detect possible deviations from the latter. In this context, a recent white paper from the Cerebrovascular Research Network focused on Transfer Function Analysis (TFA), which obtains frequency domain estimates of dynamic CA. In the present paper, we consider the use of time-domain techniques as an alternative approach. Due to their increased flexibility, time-domain methods enable the mitigation of measurement/physiological noise and the incorporation of nonlinearities and time variations in CA dynamics. Here, we provide practical recommendations and guidelines to support researchers and clinicians in effectively utilizing these techniques to study CA., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Purpose: After a traumatic brain injury (TBI), monitoring of both macrovascular and microvascular blood circulation can potentially yield a better understanding of pathophysiology of potential secondary brain lesions. We investigated the changes in phase shift (PS) between cardiac-induced oscillations of cerebral blood flow (CBF) measured at macro (ultrasound Doppler) and microvascular (laser Doppler) level. Further we assessed the impact of intracranial pressure (ICP) on PS in TBI patients. A secondary aim was to compare PS to TCD-derived cerebral arterial time constant (τ), a parameter that reflects the circulatory transit time., Methods: TCD blood flow velocities (FV) in the middle cerebral artery, laser Doppler blood microcirculation flux (LDF), arterial blood pressure (ABP), and ICP were monitored in 29 consecutive patients with TBI. Eight patients were excluded because of poor-quality signals. For the remaining 21 patients (median age = 23 (Q1: 20-Q3: 33); men:16,) data were retrospectively analysed. PS between the fundamental harmonics of FV and LDF signals was determined using spectral analysis. τ was estimated as a product of cerebrovascular resistance and compliance, based on the mathematical transformation of FV and ABP, ICP pulse waveforms., Results: PS was negative (median: -26 (Q1: -38-Q3: -15) degrees) indicating that pulse LDF at a heart rate frequency lagged behind TCD pulse. With rising mean ICP, PS became more negative (R = -0.51, p < 0.019) indicating that delay of LDF pulse increases. There was a significant correlation between PS and cerebrovascular time constant (R = -0.47, p = 0.03)., Conclusions: Pulse divergence between FV and LDF became greater with elevated ICP, likely reflecting prolonged circulatory travel time., (© 2024. The Author(s).)

Current guidelines suggest a target of partial pressure of carbon dioxide (PaCO 2 ) of 32-35 mmHg (mild hypocapnia) as tier 2 for the management of intracranial hypertension. However, the effects of mild hyperventilation on cerebrovascular dynamics are not completely elucidated. The aim of this study is to evaluate the changes of intracranial pressure (ICP), cerebral autoregulation (measured through pressure reactivity index, PRx), and regional cerebral oxygenation (rSO 2 ) parameters before and after induction of mild hyperventilation. Single center, observational study including patients with acute brain injury (ABI) admitted to the intensive care unit undergoing multimodal neuromonitoring and requiring titration of PaCO 2 values to mild hypocapnia as tier 2 for the management of intracranial hypertension. Twenty-five patients were included in this study (40% female), median age 64.7 years (Interquartile Range, IQR = 45.9-73.2). Median Glasgow Coma Scale was 6 (IQR = 3-11). After mild hyperventilation, PaCO 2 values decreased (from 42 (39-44) to 34 (32-34) mmHg, p < 0.0001), ICP and PRx significantly decreased (from 25.4 (24.1-26.4) to 17.5 (16-21.2) mmHg, p < 0.0001, and from 0.32 (0.1-0.52) to 0.12 (-0.03-0.23), p < 0.0001). rSO 2 was statistically but not clinically significantly reduced (from 60% (56-64) to 59% (54-61), p < 0.0001), but the arterial component of rSO 2 (ΔO 2 Hbi, changes in concentration of oxygenated hemoglobin of the total rSO 2 ) decreased from 3.83 (3-6.2) μM.cm to 1.6 (0.5-3.1) μM.cm, p = 0.0001. Mild hyperventilation can reduce ICP and improve cerebral autoregulation, with minimal clinical effects on cerebral oxygenation. However, the arterial component of rSO 2 was importantly reduced. Multimodal neuromonitoring is essential when titrating PaCO 2 values for ICP management., (© 2024. The Author(s).)

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).)

Time constant of the cerebral arterial bed (τ) is a transcranial Doppler (TCD) based metric that is expected to quantify the transit time of red blood cells from the insonation point to the arteriole-capillary boundary during a cardiac cycle. This study aims to assess the potential of τ as an early predictor of delayed cerebral ischemia (DCI). Consecutive patients (56 ± 15 years) treated for aneurysmal subarachnoid haemorrhage were included in the study. τ was assessed through a modelling approach that involved simultaneous recordings of arterial blood pressure and cerebral blood flow velocity (CBFV) from TCD's first recordings. 71 patients were included. 17 patients experienced DCI. τ was significantly shorter in patients who later developed DCI: 187 ± 64 ms vs. 249 ± 184 ms; p = 0.040 with moderate effect size (r G  = 0.24). Logistic regression showed that there was a significant association between increased CBFV, shortened τ, and the development of DCI (χ 2  = 11.54; p = 0.003) with AUC for the model 0.75. Patients who had both shortened τ and increased CBFV were 20 times more likely to develop DCI (OR = 20.4 (2.2-187.7)). Our results suggest that early alterations in τ are associated with DCI after aSAH. The highest performance of the model including both CBFV and τ may suggest the importance of both macrovascular and microvascular changes assessment., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

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).)

Objective: Different paradigms for neurocritical care of traumatic brain injury (TBI) have emerged in conjunction with advanced neuromonitoring technologies and derived metrics. The priority for optimizing these metrics is not currently clear. The goal of this study was to determine whether achieving cerebral perfusion pressure (CPPopt) also improves other metrics like brain oxygenation and brain blood flow., Methods: The authors performed a retrospective analysis of high-frequency data from patients with TBI who were treated at a single center and who had partial pressure of brain oxygen (PbtO2) measurements and/or brain blood flow measurements, while also undergoing intracranial pressure (ICP) monitoring. CPPopt was not calculated or targeted during patient care, but was retrospectively computed, as was the difference between the observed CPP and CPPopt., Results: A total of 22 patients with ICP, PbtO2, and/or brain blood flow monitoring were included in the analysis, and 245.7 days of measurements obtained every second were analyzed including 6,748,866 PbtO2 measurements, 3,296,405 blood flow measurements, and 10,264,770 ICP measurements. The data obtained every second were averaged by minute for analysis. In summative data, PbtO2 measurements peaked near CPPopt and were not improved above CPPopt. Blood flow measurements remained stable near CPPopt, decreased below it, and increased when CPP exceeded CPPopt. ICP decreased linearly with CPP without a specific relationship with CPPopt. In an inverse analysis, the percentage of CPP values at CPPopt, although significantly higher on the favorable side of contemporary treatment thresholds of PbtO2, ICP, and blood flow, was not found to be strongly correlated with the mean values of the physiological measurements obtained every minute (r = 0.27, r = 0.11, and r = 0.47 for ICP, PbtO2, and blood flow, respectively; p < 0.0001)., Conclusions: Although CPPopt was not targeted in the patients in this study, CPPopt was a physiologically significant value based on concurrent measurements of PbtO2 and blood flow. In summative data, achievement of CPPopt was associated with optimized PbtO2 and blood flow. Conversely, the correlation between achievement of CPPopt and the mean measurement value was not strong, strengthening the significance of CPPopt. In individual patients, achieving CPPopt is not always associated with optimal PbtO2 or blood flow. Further research should explore these relationships in treatment paradigms that specifically target CPPopt. These data do not support the premise that targeting and achieving CPPopt obviates the need for concurrent PbtO2 and blood flow monitoring. Although these data suggest that targeting CPPopt may be an appropriate initial treatment strategy, they do not provide evidence that CPPopt should be targeted with highest priority.

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).)

In this Pro-Con commentary article, we discuss whether the lower limit of cerebral autoregulation is clinically relevant for anesthesiologists. The central question regarding this issue is whether mean arterial blood pressure below the lower limit of autoregulation is detrimental for the brain. The Pro side argues that continuous monitoring of cerebral autoregulation has revealed an association between going below the lower limit and mortality in the critically ill patient. Conversely, the Con side argues that cerebral autoregulation is only one of various defense mechanisms of the brain that protect against cerebral hypoperfusion, and that cerebral autoregulation may be more important to protect against intracranial hypertension., Competing Interests: Conflicts of Interest: See Disclosures at the end of the article., (Copyright © 2022 International Anesthesia Research Society.)

Objective. Analysis of relative changes in the shapes of pulse waveforms of intracranial pressure (ICP) and transcranial Doppler cerebral blood flow velocity (CBFV) may provide information on intracranial compliance. We tested this hypothesis, introducing an index named the ratio of pulse slopes (RPS) that is based on inclinations of the ascending parts of the ICP and CBFV pulse waveforms. It has hypothetically a simple interpretation: a value of 1 indicates good compliance and a value less than 1, reduced compliance. Here, we investigated the usefulness of RPS for assessment of intracranial compliance. Approach. ICP and CBFV signals recorded simultaneously in 30 normal-pressure hydrocephalus patients during infusion tests were retrospectively analysed. CBFV was measured in the middle cerebral artery. Changes in RPS during the test were compared with changes in the height ratio of the first and second peak of the ICP pulse (P1/P2) and the shape of the ICP pulse was classified from normal (1) to pathological (4). Values are medians (lower, upper quartiles). Main results. There was a significant correlation between baseline RPS and intracranial elasticity ( R  = -0.55, p  = 0.0018). During the infusion tests, both RPS and P1/P2 decreased with rising ICP [RPS, 0.80 (0.56, 0.92) versus 0.63 (0.44, 0.80), p  = 0.00015; P1/P2, 0.58 (0.50, 0.91) versus 0.52 (0.36, 0.71), p  = 0.00009] while the ICP pulses became more pathological in shape [class: 3 (2, 3) versus 3 (3, 4), p  = 0.04]. The magnitude of the decrease in RPS during infusion was inversely correlated with baseline P1/P2 ( R  = -0.40, p  < 0.03). Significance. During infusion, the slopes of the ascending parts of ICP and CBFV pulses become increasingly divergent with a shift in opposite directions. RPS seems to be a promising methodological tool for monitoring intracranial compliance with no additional volumetric manipulation required., (Creative Commons Attribution license.)

Purpose: To study three different methods of monitoring cerebral autoregulation in children with severe traumatic brain injury., Methods: Prospective cohort study of all children admitted to the pediatric intensive care unit at a university-affiliated hospital with severe TBI over a 4-year period to study three different methods of monitoring cerebral autoregulation: pressure-reactivity index (PRx), transcranial Doppler derived mean flow velocity index (Mx), and near-infrared spectroscopy derived cerebral oximetry index (COx)., Results: Twelve patients were included in the study, aged 5 months to 17 years old. An empirical regression analyzing dependence of PRx on cerebral perfusion pressure (CPP) displayed the classic U-shaped distribution, with low PRx values (< 0.3) reflecting intact auto-regulation, within the CPP range of 50-100 mmHg. The optimal CPP was 75-80 mmHg for PRx and COx. The correlation coefficients between the three indices were as follows: PRx vs Mx, r = 0.56; p < 0.0001; PRx vs COx, r = 0.16; p < 0.0001; and COx vs Mx, r = 0.15; p = 0.022. The mean PRx with a cutoff value of 0.3 predicted correctly long-term outcome (p = 0.015)., Conclusions: PRx seems to be the most robust index to access cerebrovascular reactivity in children with TBI and has promising prognostic value. Optimal CPP calculation is feasible with PRx and COx., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Cerebrospinal compliance describes the ability of the cerebrospinal space to buffer changes in volume. Diminished compliance is associated with increased risk of potentially threatening increases in intracranial pressure (ICP) when changes in cerebrospinal volume occur. However, despite various methods of estimation proposed so far, compliance is seldom used in clinical practice. This study aimed to compare three measures of cerebrospinal compliance., Methods: ICP recordings from 36 normal-pressure hydrocephalus patients who underwent infusion tests with parallel recording of transcranial Doppler blood flow velocity were retrospectively analysed. Three methods were used to calculate compliance estimates during changes in the mean ICP induced by infusion of fluid into the cerebrospinal fluid space: (a) based on Marmarou's model of cerebrospinal fluid dynamics (C CSF ), (b) based on the evaluation of changes in cerebral arterial blood volume (C CaBV ), and (c) based on the amplitudes of peaks P1 and P2 of ICP pulse waveform (C P1/P2 )., Results: Increase in ICP caused a significant decrease in all compliance estimates (p < 0.0001). Time courses of compliance estimators were strongly positively correlated with each other (group-averaged Spearman correlation coefficients: 0.94 [0.88-0.97] for C CSF vs. C CaBV , 0.77 [0.63-0.91] for C CSF vs. C P1/P2 , and 0.68 [0.48-0.91] for C CaBV vs. C P1/P2 )., Conclusions: Indirect methods, C CaBV and C P1/P2 , allow for the assessment of relative changes in cerebrospinal compliance and produce results exhibiting good correlation with the direct method of volumetric manipulation. This opens the possibility of monitoring relative changes in compliance continuously.

The role of extra-cranial injury burden and systemic injury response on cerebrovascular response in traumatic brain injury (TBI) is poorly documented. This study preliminarily assesses the association between admission features of extra-cranial injury burden on cerebrovascular reactivity. Using the Collaborative European Neurotrauma Effectiveness Research in TBI High-Resolution ICU (HR ICU) sub-study cohort, we evaluated those patients with both archived high-frequency digital intra-parenchymal intra-cranial pressure monitoring data of a minimum of 6 h in duration, and the presence of a digital copy of their admission computed tomography (CT) scan. Digital physiologic signals were processed for pressure reactivity index (PRx) and both the percent time above defined PRx thresholds and mean hourly dose above threshold. This was conducted for both the first 72 h and entire duration of recording. Admission extra-cranial injury characteristics and CT injury scores were obtained from the database, with quantitative contusion, edema, intraventricular hemorrhage, and extra-axial lesion volumes were obtained via semi-automated segmentation. Comparison between admission extra-cranial markers of injury and PRx metrics was conducted using Mann-Whitney U testing, and logistic regression techniques, adjusting for known CT injury metrics associated with impaired PRx. A total of 165 patients were included. Evaluating the entire ICU recording period, there was limited association between metrics of extra-cranial injury burden and impaired cerebrovascular reactivity. Using the first 72 h of recording, admission temperature ( p  = 0.042) and white blood cell % (WBC %; p  = 0.013) were statistically associated with impaired cerebrovascular reactivity on Mann-Whitney U and univariate logistic regression. After adjustment for admission age, pupillary status, GCS motor score, pre-hospital hypoxia/hypotension, and intra-cranial CT characteristics associated with impaired reactivity, temperature ( p  = 0.021) and WBC % ( p  = 0.013) remained significantly associated with mean PRx values above +0.25 and +0.35, respectively. Markers of extra-cranial injury burden and systemic injury response do not appear to be strongly associated with impaired cerebrovascular reactivity in TBI during both the initial and entire ICU stay.

Objectives: Monitoring cerebral autoregulation may help identify the lower limit of autoregulation in individual patients. Mean arterial blood pressure below lower limit of autoregulation appears to be a risk factor for postoperative acute kidney injury. Cerebral autoregulation can be monitored in real time using correlation approaches. However, the precise thresholds for different cerebral autoregulation indexes that identify the lower limit of autoregulation are unknown. We identified thresholds for intact autoregulation in patients during cardiopulmonary bypass surgery and examined the relevance of these thresholds to postoperative acute kidney injury., Design: A single-center retrospective analysis., Setting: Tertiary academic medical center., Patients: Data from 59 patients was used to determine precise cerebral autoregulation thresholds for identification of the lower limit of autoregulation. These thresholds were validated in a larger cohort of 226 patients., Methods and Main Results: Invasive mean arterial blood pressure, cerebral blood flow velocities, regional cortical oxygen saturation, and total hemoglobin were recorded simultaneously. Three cerebral autoregulation indices were calculated, including mean flow index, cerebral oximetry index, and hemoglobin volume index. Cerebral autoregulation curves for the three indices were plotted, and thresholds for each index were used to generate threshold- and index-specific lower limit of autoregulations. A reference lower limit of autoregulation could be identified in 59 patients by plotting cerebral blood flow velocity against mean arterial blood pressure to generate gold-standard Lassen curves. The lower limit of autoregulations defined at each threshold were compared with the gold-standard lower limit of autoregulation determined from Lassen curves. The results identified the following thresholds: mean flow index (0.45), cerebral oximetry index (0.35), and hemoglobin volume index (0.3). We then calculated the product of magnitude and duration of mean arterial blood pressure less than lower limit of autoregulation in a larger cohort of 226 patients. When using the lower limit of autoregulations identified by the optimal thresholds above, mean arterial blood pressure less than lower limit of autoregulation was greater in patients with acute kidney injury than in those without acute kidney injury., Conclusions: This study identified thresholds of intact and impaired cerebral autoregulation for three indices and showed that mean arterial blood pressure below lower limit of autoregulation is a risk factor for acute kidney injury after cardiac surgery., Competing Interests: Drs. Lee, Hogue, and Brown received support for article research from the National Institutes of Health (NIH). Dr. Lee has received support from and been a paid consultant for Medtronic, and she received research support from Edwards Life Sciences. Dr. Lee’s arrangements have been reviewed and approved by the Johns Hopkins University in accordance with its conflict of interest policies. Some methods used to measure and monitor autoregulation as described in this article were patented by The Johns Hopkins University, listing Dr. Brady as a coinventor. These patents are exclusively licensed to Medtronic. Dr. Brown reported receiving grants from the NIH during the conduct of the study, and consulting for and participating in a data share with Medtronic. Dr. Brady is listed as inventor on patents awarded and assigned to the Johns Hopkins University. These patents are related to the monitoring technology described in this article and are exclusively licensed to Medtronic, and Dr. Brady received a portion of the licensing fee. Dr. Venkataraman received funding from Vixiar Medical (consulting) and from universities for speaker honorariums, and she was supported by the National Science Foundation CAREER award 1845430. Dr. Hogue reported receiving grants and personal fees for being a consultant and providing lectures for Medtronic/Covidien, being a consultant to Merck, and receiving grants from the NIH outside of the submitted work, and he disclosed off-label product use of autoregulation monitoring is investigational. Drs. Czosnyka and Smielewski received funding from licensing ICM+ through Cambridge Enterprise Ltd, United Kingdom. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2020 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Introduction: Adequate cerebral perfusion prevents secondary insult after traumatic brain injury (TBI). Cerebral autoregulation (CAR) keeps cerebral blood flow (CBF) constant when arterial blood pressure (ABP) changes. Aim of the study was to evaluate the existence of delayed CAR in TBI patients and its possible association with outcome., Methods: We retrospectively analysed TBI patients. Flow velocity (FV) in middle cerebral artery, invasive intra-cranial pressure (ICP) and ABP were recorded. Cerebral perfusion pressure (CPP) was calculated as ABP - ICP. Mean flow index (Mx) > 0.3 defined altered CAR. Samples from patients with altered CAR were further analysed: FV signal was shifted backward relative to CPP; Mx was calculated after each shift (MxD). Mx > 0.3 plus MxD ≤ 0.3 defined delayed CAR. Favourable outcome (FO) at 6 months was defined as Glasgow Outcome Scale 4-5., Results: 154 patients were included. GCS was 6 [4-9], ICP was 14 [9-20] mmHg. Data on 6 months outcome were available for 131 patients: 104/131 patients (79 %) were alive; GOS was 4 [3-5]; 70/131 (53 %) had FO. Mx was 0.07 [-0.19 to 0.28] overall. Mx was lower in patients with FO compared others (0.00 [-0.21 to 0.20] vs 0.17 [-0.12 to 0.37], p = 0.02). 118 (77 %) patients had intact CAR and 36 (23 %) patients had altered CAR; 23 patients - 15 % of the general cohort and 64 % of patients with altered CAR - had delayed CAR. Delay in the autoregulatory response was 2 [1-4] seconds. 80/98 (82 %) of patients with intact CAR survived, compared to 16/21 (76 %) with delayed and 8/12 (67 %) with altered CAR (p = 0.20). 80/98 (58 %) patients with intact, 10/21 (48 %) patients with delayed and 3/12 (25 %) patients with altered CAR had FO (p = 0.03)., Conclusion: A subgroup of TBI patients with delayed CAR was identified. Delayed CAR was associated with better neurological outcome than altered CAR., (Copyright © 2021. Published by Elsevier B.V.)

Transcranial Doppler ultrasound (TCD) enables assessment of brain hemodynamics through insonation of cerebral arteries and veins. Few studies have investigated whether the normal ranges of flow velocities in both arterial and venous compartments may be affected by age and sex.The purpose of this study was to determine the normal blood flow velocities across different sex and age subgroups in a cohort of healthy volunteers by studying the middle cerebral arteries (MCAs) and the straight sinus (SS).A total of 122 healthy volunteers undergoing preanesthetic assessment were recruited at Galliera Hospital in Genoa, Italy. The cohort was stratified for sex (males and females) and for age (18-44 years, 45-64 years, and ≥65 years). Data on systolic, diastolic, and mean flow velocities (FVs, FVd, and FVm, respectively) in the MCA and peak venous flow velocity in the SS (FVVs) were collected from each volunteer.The arterial FVs and FVm were significantly higher in males than in females; FVs, FVm, FVd, and FVVs increased across the age spectrum, especially in the elderly female population.Our findings suggest that there are differences in cerebrovascular flow velocities due to age and sex, which may be correlated to hormonal variations during the lifespan.

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.

Continuous measurement of cerebral blood flow velocity (CBFV) of the middle cerebral artery (MCA) using transcranial Doppler (TCD) and arterial blood pressure (ABP) monitoring enables assessment of cerebrovascular haemodynamics. Further indices describing cerebrovascular function can be calculated from ABP and CBFV, such as the mean index (Mxa) of cerebrovascular autoregulation, the 'time constant of the cerebral arterial bed' (tau), the 'critical closing pressure' (CrCP) and a 'non-invasive estimator of ICP' (nICP). However, TCD is operator-dependent and changes in angle and depth of MCA insonation result in different readings of CBFV. The effect of differing CBFV readings on the calculated secondary indices remains unknown. The aim of this study was to investigate variation in angle and depth of MCA insonation on these secondary indices. In eight patients continuous ABP and ipsilateral CBFV monitoring was performed using two different TCD probes, resulting in four simultaneous CBFV readings at different angles and depths per patient. From all individual recordings, the K-means clustering algorithm was applied to the four simultaneous longitudinal measurements. The average ratios of the between-clusters, sum-of-squares and total sum-of-squares were significantly higher for CBFV than for the indices Mxa, tau and CrCP (p < 0.001, p = 0.007 and p = 0.016) but not for nICP (p = 0.175). The results indicate that Mxa, tau and CrCP seemed to be not affected by depth and angle of TCD insonation, whereas nICP was., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: To date, the cerebral physiologic consequences of persistently elevated intracranial pressure (ICP) have been based on either low-resolution physiologic data or retrospective high-frequency data from single centers. The goal of this study was to provide a descriptive multi-center analysis of the cerebral physiologic consequences of ICP, comparing those with normal ICP to those with elevated ICP., Methods: The Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) High-Resolution Intensive Care Unit (HR-ICU) sub-study cohort was utilized. The first 3 days of physiologic recording were analyzed, evaluating and comparing those patients with mean ICP < 15 mmHg versus those with mean ICP > 20 mmHg. Various cerebral physiologic parameters were derived and evaluated, including ICP, brain tissue oxygen (PbtO 2 ), cerebral perfusion pressure (CPP), pulse amplitude of ICP (AMP), cerebrovascular reactivity, and cerebral compensatory reserve. The percentage time and dose above/below thresholds were also assessed. Basic descriptive statistics were employed in comparing the two cohorts., Results: 185 patients were included, with 157 displaying a mean ICP below 15 mmHg and 28 having a mean ICP above 20 mmHg. For admission demographics, only admission Marshall and Rotterdam CT scores were statistically different between groups (p = 0.017 and p = 0.030, respectively). The high ICP group displayed statistically worse CPP, PbtO 2 , cerebrovascular reactivity, and compensatory reserve. The high ICP group displayed worse 6-month mortality (p < 0.0001) and poor outcome (p = 0.014), based on the Extended Glasgow Outcome Score., Conclusions: Low versus high ICP during the first 72 h after moderate/severe TBI is associated with significant disparities in CPP, AMP, cerebrovascular reactivity, cerebral compensatory reserve, and brain tissue oxygenation metrics. Such ICP extremes appear to be strongly related to 6-month patient outcomes, in keeping with previous literature. This work provides multi-center validation for previously described single-center retrospective results.

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 .

Objective: The time constant of the cerebral arterial bed (τ), which is an index of brain haemodynamics, can be estimated in patients using continuous monitoring of arterial blood pressure (ABP), transcranial Doppler cerebral blood flow velocity (CBFV) and intracranial pressure (ICP) if these measures are available. But, in some clinical scenarios invasive measurement of ABP is not feasible. Therefore, in this study we aimed to investigate whether invasive ABP can be replaced with non-invasive ABP, monitored using the Finapres photoplethysmograph (fABP)., Approach: Forty-six recordings of ICP, ABP, fABP, and CBFV in the right and left middle cerebral arteries were performed daily for approximately 30 min in 10 head injury patients. Two modelling approaches (constant flow forward [CFF, pulsatile blood inflow and steady blood outflow] and pulsatile flow forward [PFF, where both blood inflow and outflow are pulsatile]) were applied to estimate τ using either invasive ABP (τ CFF , τ PFF ) or non-invasive ABP (fτ CFF , fτ PFF )., Main Results: Bland-Altman analysis showed quite poor agreement between the fτ and τ methods of estimation. The fτ method produced significantly higher values than the τ method when calculated using both the CFF and PFF models (p < .001 for both). The correlation between fτ CFF and τ CFF was moderately high (r s = 0.63; p < .001), whereas that between fτ PFF and τ PFF was weaker (r s = 0.40; p = .009)., Significance: Our results suggest that using non-invasive ABP for estimation of τ is inaccurate in head injury patients.

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.

Failure of cerebral autoregulation has been linked to unfavorable outcome after traumatic brain injury (TBI). Preliminary evidence from a small, retrospective, single-center analysis suggests that autoregulatory dysfunction may be associated with traumatic lesion expansion, particularly for pericontusional edema. The goal of this study was to further explore these associations using prospective, multi-center data from the Collaborative European Neurotrauma Effectiveness Research in TBI (CENTER-TBI) and to further explore the relationship between autoregulatory failure, lesion progression, and patient outcome. A total of 88 subjects from the CENTER-TBI High Resolution ICU Sub-Study cohort were included. All patients had an admission computed tomography (CT) scan and early repeat scan available, as well as high-frequency neurophysiological recordings covering the between-scan interval. Using a novel, semiautomated approach at lesion segmentation, we calculated absolute changes in volume of contusion core, pericontusional edema, and extra-axial hemorrhage between the imaging studies. We then evaluated associations between cerebrovascular reactivity metrics and radiological lesion progression using mixed-model regression. Analyses were adjusted for baseline covariates and non-neurophysiological factors associated with lesion growth using multi-variate methods. Impairment in cerebrovascular reactivity was significantly associated with progression of pericontusional edema and, to a lesser degree, intraparenchymal hemorrhage. In contrast, there were no significant associations with extra-axial hemorrhage. The strongest relationships were observed between RAC-based metrics and edema formation. Pulse amplitude index showed weaker, but consistent, associations with contusion growth. Cerebrovascular reactivity metrics remained strongly associated with lesion progression after taking into account contributions from non-neurophysiological factors and mean cerebral perfusion pressure. Total hemorrhagic core and edema volumes on repeat CT were significantly larger in patients who were deceased at 6 months, and the amount of edema was greater in patients with an unfavourable outcome (Glasgow Outcome Scale-Extended 1-4). Our study suggests associations between autoregulatory failure, traumatic edema progression, and poor outcome. This is in keeping with findings from a single-center retrospective analysis, providing multi-center prospective data to support those results.

Decompressive craniectomy (DC) in traumatic brain injury (TBI) has been suggested to influence cerebrovascular reactivity. We aimed to determine if the statistical properties of vascular reactivity metrics and slow-wave relationships were impacted after DC, as such information would allow us to comment on whether vascular reactivity monitoring remains reliable after craniectomy. Using the CENTER-TBI High Resolution Intensive Care Unit (ICU) Sub-Study cohort, we selected those secondary DC patients with high-frequency physiological data for both at least 24 h pre-DC, and more than 48 h post-DC. Data for all physiology measures were separated into the 24 h pre-DC, the first 48 h post-DC, and beyond 48 h post-DC. We produced slow-wave data sheets for intracranial pressure (ICP) and mean arterial pressure (MAP) per patient. We also derived a Pressure Reactivity Index (PRx) as a continuous cerebrovascular reactivity metric updated every minute. The time-series behavior of the PRx was modeled for each time period per patient. Finally, the relationship between ICP and MAP during these three time periods was assessed using time-series vector autoregressive integrative moving average (VARIMA) models, impulse response function (IRF) plots, and Granger causality testing. Ten patients were included in this study. Mean PRx and proportion of time above PRx thresholds were not affected by craniectomy. Similarly, PRx time-series structure was not affected by DC, when assessed in each individual patient. This was confirmed with Granger causality testing, and VARIMA IRF plotting for the MAP/ICP slow-wave relationship. PRx metrics and statistical time-series behavior appear not to be substantially influenced by DC. Similarly, there is little change in the relationship between slow waves of ICP and MAP before and after DC. This may suggest that cerebrovascular reactivity monitoring in the setting of DC may still provide valuable information regarding autoregulation.

The time constant of the cerebral arterial bed ("tau") estimates how fast the blood entering the brain fills the arterial vascular sector. Analogous to an electrical resistor-capacitor circuit, it is expressed as the product of arterial compliance (Ca) and cerebrovascular resistance (CVR). Hypocapnia increases the time constant in healthy volunteers and decreases arterial compliance in head trauma. How the combination of hyocapnia and trauma affects this parameter has yet to be studied. We hypothesized that in TBI patients the intense vasoconstrictive action of hypocapnia would dominate over the decrease in compliance seen after hyperventilation. The predominant vasoconstrictive response would maintain an incoming blood volume in the arterial circulation, thereby lengthening tau. We retrospectively analyzed recordings of intracranial pressure (ICP), arterial blood pressure (ABP), and blood flow velocity (FV) obtained from a cohort of 27 severe TBI patients [(39/30 years (median/IQR), 5 women; admission GCS 6/5 (median/IQR)] studied during a standard clinical CO 2 reactivity test. The reactivity test was performed by means of a 50-min increase in ventilation (20% increase in respiratory minute volume). CVR and Ca were estimated from these recordings, and their product calculated to find the time constant. CVR significantly increased [median CVR pre-hypocapnia/during hypocapnia: 1.05/1.35 mmHg/(cm 3 /s)]. Ca decreased (median Ca pre-hypocapnia/during hypocapnia: 0.130/0.124 arbitrary units) to statistical significance (p = 0.005). The product of these two parameters resulted in a significant prolongation of the time constant (median tau pre-hypocapnia/during hypocapnia: 0.136 s/0.152 s, p ˂ .001). Overall, the increase in CVR dominated over the decrease in compliance, hence tau was longer. We demonstrate a significant increase in the time constant of the cerebral circulation during hypocapnia after severe TBI, and attribute this to an increase in cerebrovascular resistance which outweighs the decrease in cerebral arterial bed compliance.

Objective: The study objective was to investigate outcomes associated with the application of bilateral or unilateral antegrade cerebral perfusion during surgery for acute type A dissection., Methods: Patients who underwent surgery for type A dissection with the application of antegrade cerebral perfusion between 2009 and 2017 at the Division of Cardiac Surgery, Medical University of Vienna were analyzed retrospectively (bilateral antegrade cerebral perfusion: n = 91, 49.5%; unilateral antegrade cerebral perfusion: n = 93, 50.5%). The primary outcome variable was overall survival. Subgroup analyses were performed in patients requiring antegrade cerebral perfusion durations of 50 minutes or more and less than 50 minutes. Secondary outcome variables were 30-day mortality, adverse outcome, permanent and temporary neurologic deficits, renal replacement therapy, prolonged ventilation, intensive care unit stay, and hospital stay., Results: Multivariable Cox proportional hazards analysis demonstrated no significant association of bilateral antegrade cerebral perfusion with overall survival (hazard ratio, 0.63; 95% confidence interval, 0.34-1.14, P = .126). Propensity score modeling using the method of inverse probability of treatment weighting confirmed this result (hazard ratio, 0.73; 95% confidence interval, 0.33-1.60, P = .428). Bilateral antegrade cerebral perfusion was associated with significantly improved overall survival in patients requiring antegrade cerebral perfusion durations of 50 minutes or more (P = .017). The bilateral antegrade cerebral perfusion and unilateral antegrade cerebral perfusion groups showed comparable rates of secondary outcome variables., Conclusions: In the present study, bilateral antegrade cerebral perfusion and unilateral antegrade cerebral perfusion are associated with comparable outcomes after surgery for type A dissection. Subgroup analyses suggest that bilateral antegrade cerebral perfusion is associated with superior overall survival in patients requiring antegrade cerebral perfusion durations of 50 minutes or more. An adequately powered prospective randomized controlled trial is required to validate these results., (Copyright © 2019 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

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.

Objectives : The critical closing pressure (CrCP) defines arterial blood pressure below which cerebral arteries collapse. It represents a clinically relevant parameter for the estimation of cerebrovascular tone. Although there are few methods to assess CrCP, there is no consensus which of them estimates this parameter most accurately. The aim of present retrospective, experimental study was to compare three methods of CrCP estimation: conventional Aaslid's formula and methods based on the cerebrovascular impedance: the established continuous flow forward (CFF) and a new pulsatile flow forward (PFF) model. Methods : The effects of the following physiological manoeuvres on the CrCP were studied in New Zealand white rabbits: lumbar infusion of Hartmann's solution to induce mild intracranial hypertension, sympathetic blockade to induce arterial hypotension, and modulation of respiratory tidal volume to induce hypocapnia or hypercapnia. Results : During intracranial hypertension, all CrCP estimates were significantly higher than at baseline, decreased with decreasing ABP and increased with gradual hypocapnia. During hypercapnia, all CrCP estimates were significantly decreased but only in the case of CrCP A the negative, non-physiological values were observed (16% of the cases). The Bland-Altman analysis revealed that a good agreement between each impedance method and Aaslid's method deteriorated significantly in the low range of the average numerical value of the estimates. Discussion : Our results confirm the limited usage of Aaslid's formula for the calculation of CrCP. Although both impedance methods seem to be equivalent, the fact that PFF model better describes cerebrovascular hemodynamic allows the recommendation of this model for the calculation of CrCP.

Existing cerebrovascular blood pressure autoregulation metrics have not been translated to clinical care for pediatric cardiac arrest, in part because signal noise causes high index time-variability. We tested whether a wavelet method that uses near-infrared spectroscopy (NIRS) or intracranial pressure (ICP) decreases index variability compared to that of commonly used correlation indices. We also compared whether the methods identify the optimal arterial blood pressure (ABPopt) and lower limit of autoregulation (LLA). 68 piglets were randomized to cardiac arrest or sham procedure with continuous monitoring of cerebral blood flow using laser Doppler, NIRS and ICP. The arterial blood pressure (ABP) was gradually reduced until it dropped to below the LLA. Several autoregulation indices were calculated using correlation and wavelet methods, including the pressure reactivity index (PRx and wPRx), cerebral oximetry index (COx and wCOx), and hemoglobin volume index (HVx and wHVx). Wavelet methodology had less index variability with smaller standard deviations. Both wavelet and correlation methods distinguished functional autoregulation (ABP above LLA) from dysfunctional autoregulation (ABP below the LLA). Both wavelet and correlation methods also identified ABPopt with high agreement. Thus, wavelet methodology using NIRS may offer an accurate vasoreactivity monitoring method with reduced signal noise after pediatric cardiac arrest.

Purpose of Review: This review summarizes the physiological basis of autoregulation-oriented therapy in critically ill patients, with a particular emphasis on individual targets based on parameters that describe autoregulation of cerebral blood flow., Recent Findings: The concepts of optimal cerebral perfusion (CPPopt) and arterial pressures (ABPopt), which both take advantage of continuous measures of cerebral autoregulation, recently have been introduced into clinical practice. It is hypothesized that if both pressures are used as individual targets and followed, the incidence and severity of dysautoregulation will diminish sufficiently to improve outcomes across the spectrum of acute neurological illnesses. These parameters have not been tested in randomized trials. However, a Phase II trial for CPPopt in Traumatic Brain Injury (COGITATE) is underway. Clinical series suggest that delirium following cardiac surgery may be reduced if blood pressure is actively regulated above the lower limit of autoregulation. In traumatic brain injury, using CPPopt as a single target allows monitoring of the upper and lower limits of autoregulation that provide a well tolerated 'corridor' for treatment. Pilot studies in which ABPopt is monitored in preterm newborns suggest fewer haemorrhagic events if blood pressure is closer to its optimal target. Brain imaging studies suggest worse tissue outcomes when blood pressure is below ABPopt., Summary: Targeted control of brain and systemic blood pressures to optimize cerebral autoregulation is of substantial interest to the neurocritical care and anaesthesia community, as this strategy may help to avoid secondary brain insults associated with ischemia or hyperaemia. The same strategy can be used outside the ICU (e.g. cardiac surgery, or in stroke patients after mechanical thrombectomy); this requires further research.

Background: Raised intracranial pressure (ICP) is a prominent cause of morbidity and mortality after severe traumatic brain injury (TBI). However, in the clinical setting, little is known about the cerebral physiological response to severe and prolonged increases in ICP., Methods: Thirty-three severe TBI patients from a single center who developed severe refractory intracranial hypertension (ICP > 40 mm Hg for longer than 1 h) with ICP, arterial blood pressure, and brain tissue oxygenation (P BT O 2 ) monitoring (subcohort, n = 9) were selected for retrospective review. Secondary parameters reflecting autoregulation (including pressure reactivity index-PRx, which was available in 24 cases), cerebrospinal compensatory reserve (RAP), and ICP pulse amplitude were calculated., Results: PRx deteriorated from 0.06 ± 0.26 a.u. at baseline levels of ICP to 0.57 ± 0.24 a.u. (p < 0.0001) at high levels of ICP (> 50 mm Hg). In 4 cases, PRx was impaired (> 0.25 a.u.) before ICP was raised above 25 mm Hg. Concurrently, P BT O 2 decreased from 27.3 ± 7.32 mm Hg at baseline ICP to 12.68 ± 7.09 mm Hg at high levels of ICP (p < 0.001). The pulse amplitude of the ICP waveform increased with increasing ICP but showed an 'upper breakpoint'-whereby further increases in ICP lead to decreases in pulse amplitude-in 6 out of the 33 patients., Discussion: Severe intracranial hypertension after TBI leads to decreased brain oxygenation, impaired pressure reactivity, and changes in the pulse amplitude of ICP. Impaired pressure reactivity may denote increased risk of developing refractory intracranial hypertension in some patients.

Background: Failure of cerebral autoregulation and progression of intracranial lesion have both been shown to contribute to poor outcome in patients with acute traumatic brain injury (TBI), but the interplay between the two phenomena has not been investigated. Preliminary evidence leads us to hypothesize that brain tissue adjacent to primary injury foci may be more vulnerable to large fluctuations in blood flow in the absence of intact autoregulatory mechanisms. The goal of this study was therefore to assess the influence of cerebrovascular reactivity measures on radiological lesion expansion in a cohort of patients with acute TBI., Methods: We conducted a retrospective cohort analysis on 50 TBI patients who had undergone high-frequency multimodal intracranial monitoring and for which at least two brain computed tomography (CT) scans had been performed in the acute phase of injury. We first performed univariate analyses on the full cohort to identify non-neurophysiological factors (i.e., initial lesion volume, timing of scan, coagulopathy) associated with traumatic lesion growth in this population. In a subset analysis of 23 patients who had intracranial recording data covering the period between the initial and repeat CT scan, we then correlated changes in serial volumetric lesion measurements with cerebrovascular reactivity metrics derived from the pressure reactivity index (PRx), pulse amplitude index (PAx), and RAC (correlation coefficient between the pulse amplitude of intracranial pressure and cerebral perfusion pressure). Using multivariate methods, these results were subsequently adjusted for the non-neurophysiological confounders identified in the univariate analyses., Results: We observed significant positive linear associations between the degree of cerebrovascular reactivity impairment and progression of pericontusional edema. The strongest correlations were observed between edema progression and the following indices of cerebrovascular reactivity between sequential scans: % time PRx > 0.25 (r = 0.69, p = 0.002) and % time PAx > 0.25 (r = 0.64, p = 0.006). These associations remained significant after adjusting for initial lesion volume and mean cerebral perfusion pressure. In contrast, progression of the hemorrhagic core and extra-axial hemorrhage volume did not appear to be strongly influenced by autoregulatory status., Conclusions: Our preliminary findings suggest a possible link between autoregulatory failure and traumatic edema progression, which warrants re-evaluation in larger-scale prospective studies.

This study analyzed morphometric and hemodynamic parameters of aneurysmal and non-aneurysmal middle cerebral artery (MCA) bifurcations and their relationship with optimal values derived from the principle of minimum work (PMW). The study included 96 patients with MCA aneurysm and 94 controls. Aneurysm patients presented with significantly higher values of the radius and cross-sectional area of the MCA trunk, angle between the post-bifurcation branches (α angle) and volume flow rate (VFR) and had significantly lower values of junction exponent and pulsatility index than the controls. The Φ 1 and Φ 2 angles (angles between the MCA trunk axis and the larger and smaller branch, respectively) and α angle in all groups were significantly larger than the optimal PMW-derived angles. The most important independent predictors of MCA aneurysm were junction exponent (odds ratio, OR = 0.42), α angle (OR = 1.07) and VFR (OR = 2.36). Development of cerebral aneurysms might be an independent effect of abnormalities in hemodynamic and morphometric factors. The risk of aneurysm increased proportionally to the deviation of morphometric parameters of the bifurcation from their optimal PMW-derived values. The role of bifurcation angle in aneurysm development needs to be explained in future research as the values of this parameter in both aneurysm patients and non-aneurysmal controls in were scattered considerably around the PMW-derived optimum.

Background: Two transcranial Doppler (TCD) estimators of cerebral arterial blood volume (CaBV) coexist: continuous outflow of arterial blood outside the cranium through a low-pulsatile venous system (continuous flow forward, CFF) and pulsatile outflow through regulating arterioles (pulsatile flow forward, PFF). We calculated non-invasive equivalents of the pressure reactivity index (PRx) and the pulse amplitude index PAx with slow waves of mean CaBV and its pulse amplitude., Methods: About 273 individual TBI patients were retrospectively reviewed. PRx is the correlation coefficient between 30 samples of 10-second averages of ICP and mean ABP. PAx is the correlation coefficient between 30 samples of 10-second averages of the amplitude of ICP (AMP, derived from Fourier analysis of the raw full waveform ICP tracing) and mean ABP. nPRx is calculated with CaBV instead of ICP and nPAx with the pulse amplitude of CaBV instead of AMP (calculated using both the CFF and PFF models). All reactivity indices were additionally compared with Glasgow Outcome Score (GOS) to verify potential outcome-predictive strength., Results: When correlated, slow waves of ICP demonstrated good coherence between slow waves in CaBV (>0.75); slow waves of AMP showed good coherence with slow waves of the pulse amplitude of CaBV (>0.67) in both the CFF and PFF models. nPRx was moderately correlated with PRx (R = 0.42 for CFF and R = 0.38 for PFF; p < 0.0001). nPAx correlated with PAx with slightly better strength (R = 0.56 for CFF and R = 0.41 for PFF; p < 0.0001). nPAx&#95;CFF showed the strongest association with outcomes., Conclusions: Non-invasive estimators (nPRx and nPAx) are associated with their invasive counterparts and can provide meaningful associations with outcome after TBI. The CFF model is slightly superior to the PFF model.

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.

We analysed mean arterial blood pressure, cerebral blood flow velocity, oxygenated haemoglobin and deoxygenated haemoglobin signals to estimate dynamic cerebral autoregulation. We compared macrovascular (mean arterial blood pressure-cerebral blood flow velocity) and microvascular (oxygenated haemoglobin-deoxygenated haemoglobin) dynamic cerebral autoregulation estimates during three different conditions: rest, mild hypocapnia and hypercapnia. Microvascular dynamic cerebral autoregulation estimates were created by introducing the constant time lag plus constant phase shift model, which enables correction for transit time, blood flow and blood volume oscillations (TT-BF/BV correction). After TT-BF/BV correction, a significant agreement between mean arterial blood pressure-cerebral blood flow velocity and oxygenated haemoglobin-deoxygenated haemoglobin phase differences in the low frequency band was found during rest (left: intraclass correlation=0.6, median phase difference 29.5° vs. 30.7°, right: intraclass correlation=0.56, median phase difference 32.6° vs. 39.8°) and mild hypocapnia (left: intraclass correlation=0.73, median phase difference 48.6° vs. 43.3°, right: intraclass correlation=0.70, median phase difference 52.1° vs. 61.8°). During hypercapnia, the mean transit time decreased and blood volume oscillations became much more prominent, except for very low frequencies. The transit time related to blood flow oscillations was remarkably stable during all conditions. We conclude that non-invasive microvascular dynamic cerebral autoregulation estimates are similar to macrovascular dynamic cerebral autoregulation estimates, after TT-BF/BV correction is applied. These findings may increase the feasibility of non-invasive continuous autoregulation monitoring and guided therapy in clinical situations.

Objectives: This study investigated whether comatose patients with greater duration and magnitude of clinically observed mean arterial pressure outside optimal mean arterial blood pressure have worse outcomes than those with mean arterial blood pressure closer to optimal mean arterial blood pressure calculated by bedside multimodal cerebral autoregulation monitoring using near-infrared spectroscopy., Design: Prospective observational study., Setting: Neurocritical Care Unit of the Johns Hopkins Hospital., Subjects: Acutely comatose patients secondary to brain injury., Interventions: None., Measurements and Main Results: The cerebral oximetry index was continuously monitored with near-infrared spectroscopy for up to 3 days. Optimal mean arterial blood pressure was defined as that mean arterial blood pressure at the lowest cerebral oximetry index (nadir index) for each 24-hour period of monitoring. Kaplan-Meier analysis and proportional hazard regression models were used to determine if survival at 3 months was associated with a shorter duration of mean arterial blood pressure outside optimal mean arterial blood pressure and the absolute difference between clinically observed mean arterial blood pressure and optimal mean arterial blood pressure. A total 91 comatose patients were enrolled in the study. The most common etiology was intracerebral hemorrhage. Optimal mean arterial blood pressure could be calculated in 89 patients (97%), and the median optimal mean arterial blood pressure was 89.7 mm Hg (84.6-100 mm Hg). In multivariate proportional hazard analysis, duration outside optimal mean arterial blood pressure of greater than 80% of monitoring time (adjusted hazard ratio, 2.13; 95% CI, 1.04-4.41; p = 0.04) and absolute difference between clinically observed mean arterial blood pressure and optimal mean arterial blood pressure of more than 10 mm Hg (adjusted hazard ratio, 2.44; 95% CI, 1.21-4.92; p = 0.013) were independently associated with mortality at 3 months, after adjusting for brain herniation, admission Glasgow Coma Scale, duration on vasopressors and midline shift at septum., Conclusions: Comatose neurocritically ill adults with an absolute difference between clinically observed mean arterial blood pressure and optimal mean arterial blood pressure greater than 10 mm Hg and duration outside optimal mean arterial blood pressure greater than 80% had increased mortality at 3 months. Noninvasive near-infrared spectroscopy-based bedside calculation of optimal mean arterial blood pressure is feasible and might be a promising tool for cerebral autoregulation oriented-therapy in neurocritical care patients.

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: Asymmetry of cerebral autoregulation (CA) was demonstrated in patients after aneurysmal subarachnoid haemorrhage (aSAH). A classical method for CA assessment requires simultaneous measurement of both arterial blood pressure (ABP) and cerebral blood flow velocity (CBFV). In this study, we have proposed a cerebral blood flow asymmetry index based only on CBFV and analysed its association with the occurrence of vasospasm after aSAH., New Method: The phase shifts (PS) between slow oscillations in left and right CBFV (side-to-side PS) and between ABP and CBFV (CBFV-ABP PS) were estimated using multichannel matching pursuit (MMP) and cross-spectral analysis., Results: We retrospectively analysed data collected from 45 aSAH patients (26 with vasospasm). Data were analysed up to 7th day after aSAH unless the vasospasm was detected earlier. A progressive asymmetry, manifested by a gradual increase in side-to-side PS on consecutive days after aSAH, was observed in patients who developed vasospasm (R adj 2  = 0.14, p = 0.009). In these patients, early side-to-side PS was more positive than in patients without vasospasm (2.8° ± 5.6° vs -1.7° ± 5.7°, p = 0.011). No such a difference was found in CBFV-ABP PS. Patients with positive side-to-side PS were more likely to develop vasospasm than patients with negative side-to-side PS (21/7 vs 5/12, p = 0.0047)., Comparison With Existing Method: MMP, in contrast to the spectral approach, accounts for non-stationarity of analysed signals. MMP applied to the PS estimation reflects the cerebral blood flow asymmetry in aSAH better than the spectral analysis., Conclusions: Changes in side-to-side PS might be helpful to identify patients who are at risk of vasospasm., (Copyright © 2019 Elsevier B.V. All rights reserved.)

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.

The cerebral arterial blood volume changes (∆C a BV) during a single cardiac cycle can be estimated using transcranial Doppler ultrasonography (TCD) by assuming pulsatile blood inflow, constant, and pulsatile flow forward from large cerebral arteries to resistive arterioles [continuous flow forward (CFF) and pulsatile flow forward (PFF)]. In this way, two alternative methods of cerebral arterial compliance (C a ) estimation are possible. Recently, we proposed a TCD-derived index, named the time constant of the cerebral arterial bed (τ), which is a product of C a and cerebrovascular resistance and is independent of the diameter of the insonated vessel. In this study, we aim to examine whether the τ estimated by either the CFF or the PFF model differs when calculated from the middle cerebral artery (MCA) and the posterior cerebral artery (PCA). The arterial blood pressure and TCD cerebral blood flow velocity (CBFV a ) in the MCA and in the PCA were non-invasively measured in 32 young, healthy volunteers (median age: 24, minimum age: 18, maximum age: 31). The τ was calculated using both the PFF and CFF models from the MCA and the PCA and compared using a non-parametric Wilcoxon signed-rank test. Results are presented as medians (25th-75th percentiles). The cerebrovascular time constant estimated in both arteries using the PFF model was shorter than when using the CFF model (ms): [64.83 (41.22-104.93) vs. 178.60 (160.40-216.70), p < 0.001 in the MCA, and 44.04 (17.15-81.17) vs. 183.50 (153.65-204.10), p < 0.001 in the PCA, respectively]. The τ obtained using the PFF model was significantly longer from the MCA than from the PCA, p = 0.004. No difference was found in the τ when calculated using the CFF model. Longer τ from the MCA might be related to the higher C a of the MCA than that of the PCA. Our results demonstrate MCA-PCA differences in the τ, but only when the PFF model was applied.

Background: Changes in systemic and cerebral hemodynamics in preterm infants during early transitional circulation are complex and may differ between infants with or without intraventricular hemorrhage (IVH)., Method: In total, 43 infants born at median (range) 25 + 5 (23 + 3-31) had continuous near-infrared spectroscopy (NIRS) monitoring of tissue oxygenation index (TOI) and cerebrovascular reactivity within the first 48 h of life. Measurements of left and right cardiac outputs (LVO, RVO) and patent ductus arteriosus (PDA) were collected at 6, 12, 24, and 48 h of life., Results: LVO increased within the first 48 h in the IVH (P = 0.007) and no-IVH (P < 0.001) groups. The pattern of change in LVO and RVO was not different between these two groups. TOI was lower in the IVH (P < 0.001) group. A positive correlation between TOI and LVO (P = 0.003) and a negative correlation between the tissue oxygen reactivity index (TOx) and LVO (P = 0.04) were observed at 24 h of life in the IVH group. PDA diameter was not different between IVH groups at any time interval., Conclusion: Cerebral oxygenation was lower and cerebrovascular reactivity was passive to systemic blood flow at 24 h in infants who developed an IVH.

Although the beach-chair position (BCP) is widely used during shoulder surgery, it has been reported to associate with a reduction in cerebral blood flow, oxygenation, and risk of brain ischaemia. We assessed cerebral haemodynamics using a multiparameter transcranial Doppler-derived approach in patients undergoing shoulder surgery. 23 anaesthetised patients (propofol (2 mg/kg)) without history of neurologic pathology undergoing elective shoulder surgery were included. Arterial blood pressure (ABP, monitored with a finger-cuff plethysmograph calibrated at the auditory meatus level) and cerebral blood flow velocity (FV, monitored in the middle cerebral artery) were recorded in supine and in BCP. All subjects underwent interscalene block ipsilateral to the side of FV measurement. We evaluated non-invasive intracranial pressure (nICP) and cerebral perfusion pressure (nCPP) calculated with a black-box mathematical model; critical closing pressure (CrCP); diastolic closing margin (DCM-pressure reserve available to avoid diastolic flow cessation); cerebral autoregulation index (Mxa); pulsatility index (PI). Significant changes occured for DCM [mean decrease of 6.43 mm Hg (p = 0.01)] and PI [mean increase of 0.11 (p = 0.05)]. ABP, FV, nICP, nCPP and CrCP showed a decreasing trend. Cerebral autoregulation was dysfunctional (Mxa > 0.3) and PI deviated from normal ranges (PI > 0.8) in both phases. ABP and nCPP values were low (< 60 mm Hg) in both phases. Changes between phases did not result in CrCP reaching diastolic ABP, therefore DCM did not reach critical values (≤ 0 mm Hg). BCP resulted in significant cerebral haemodynamic changes. If left untreated, reduction in cerebral blood flow may result in brain ischaemia and post-operative neurologic deficit.

Background: Intracranial pressure (ICP) is a clinically important variable after severe traumatic brain injury (TBI) and has been monitored, along with clinical outcome, for over 25 yr in Addenbrooke's hospital, Cambridge, United Kingdom. This time period has also seen changes in management strategies with the implementation of protocolled specialist neurocritical care, expansion of neuromonitoring techniques, and adjustments of clinical treatment targets., Objective: To describe the changes in intracranial monitoring variables over the past 25 yr., Methods: Data from 1146 TBI patients requiring ICP monitoring were analyzed. Monitored variables included ICP, cerebral perfusion pressure (CPP), and the cerebral pressure reactivity index (PRx). Data were stratified into 5-yr epochs spanning the 25 yr from 1992 to 2017., Results: CPP increased sharply with specialist neurocritical care management (P < 0.0001) (introduction of a specific TBI management algorithm) before stabilizing from 2000 onwards. ICP decreased significantly over the 25 yr of monitoring from an average of 19 to 12 mmHg (P < 0.0001) but PRx remained unchanged. The mean number of ICP plateau waves and the number of patients developing refractory intracranial hypertension both decreased significantly. Mortality did not significantly change in the cohort (22%)., Conclusion: We demonstrate the evolving trends in neurophysiological monitoring over the past 25 yr from a single, academic neurocritical care unit. ICP and CPP were responsive to the introduction of an ICP/CPP protocol while PRx has remained unchanged., (Copyright © 2018 by the Congress of Neurological Surgeons.)

Transcranial Doppler (TCD) ultrasonography allows continuous non-invasive monitoring of cerebral blood flow velocity in a variety of clinical conditions. Recently, signal processing of TCD signals has provided several comprehensive parameters for the assessment of cerebral haemodynamics. In this work, we applied a TCD multimodal approach in patients with acute liver failure undergoing orthotopic liver transplant (OLT) to assess the clinical feasibility of using TCD for cerebral haemodynamics assessment in this setting. We retrospectively studied six patients undergoing OLT with continuous monitoring of arterial blood pressure and blood flow velocity in the middle cerebral artery. The main cerebral haemodynamic parameters assessed were non-invasive intracranial pressure, cerebral perfusion pressure, cerebral autoregulation, pulsatility index, critical closing pressure and diastolic closing margin. TCD monitoring revealed marked alterations of these parameters in the OLT setting, which could provide relevant clinical information when there is imminent risk of neurologic impairment., (Copyright © 2019 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

Purpose: This work sought to compare a quantitative T 1 bookend dynamic susceptibility contrast MRI based perfusion protocol for absolute cerebral blood flow (qCBF) against CBF measured by the stable-isotope neutron capture microsphere method, a recognized reference standard for measuring tissue blood flow, at normocapnia, hypercapnia, and in acute stroke., Methods: CBF was measured in anesthetized female canines by MRI and microspheres over 2 consecutive days for each case. On day 1, 5 canines were measured before and during a physiological challenge induced by carbogen inhalation; on day 2, 4 canines were measured following permanent occlusion of the middle cerebral artery. CBF and cerebrovascular reactivity measured by MRI and microsphere deposition were compared., Results: MRI correlated strongly with microspheres at the hemispheric level for CBF during normo- and hypercapnic states (r 2 = 0.96), for individual cerebrovascular reactivity (r 2 = 0.84), and for postocclusion CBF (r 2 = 0.82). Correction for the delay and dispersion of the contrast bolus resulted in a significant improvement in the correlation between MRI and microsphere deposition in the ischemic state (r 2 = 0.96). In all comparisons, moderate correlations were found at the regional level., Conclusion: In an experimental canine model with and without permanent occlusion of the middle cerebral artery, MRI-based qCBF yielded moderate to strong correlations for absolute quantitative CBF and cerebrovascular reactivity measurements during normocapnia and hypercapnia. Correction for delay and dispersion greatly improved the quantitation during occlusion of the middle cerebral artery, underscoring the importance for this correction under focal ischemic condition., (© 2019 International Society for Magnetic Resonance in Medicine.)