Reliability and variability of pressure reactivity index (prx) during oscillatory pattern in arterial blood pressure and intracranial pressure in traumatic brain injured patients.

Introduction: Pressure reactivity index (PRx) is used for continuous monitoring of cerebrovascular reactivity in traumatic brain injury (TBI). However, PRx has a noisy character. Oscillations in arterial blood pressure (ABP) introduced by cyclic positive end-expiratory pressure adjustment, can make PRx more reliable. However, if oscillations are introduced by the cycling process of an anti-decubitus-mattress the effect on PRx is confounding, as they affect directly also intracranial pressure (ICP). In our routine monitoring in TBI patients we noticed periods of highly regular, slow, spontaneous oscillations in ABP and ICP signals. Research question: We set out to explore the nature of these oscillations and establish if PRx remains reliable during the oscillations. Materials and methods: 10 TBI patients' recordings with oscillations in ICP and ABP were analysed. We computed PRx, PRx variability (hourly-average of standard-deviation, SD), phase-shift and coherence between ABP and ICP in the slow frequency range. Metrics were compared between oscillation and peri-oscillation periods. Results: During oscillations (frequency 0.006 ± 0.002Hz), a significantly lower variability of PRx (SD 0.185vs0.242) and higher coherence ABP-ICP (0.618 ± 0.09 vs 0.534 ± 0.09) were observed. No external oscillations sources could be identified. 34 out of 48 events showed signs of 'active' transmission associated with negative PRx, indicating a potential positive impact on PRx reliability. Discussion and conclusions: Spontaneous oscillations observed in ABP and ICP signals were found to enhance rather than confound PRx reliability. Further research is warranted to elucidate the nature of these oscillations and develop strategies to leverage them for enhancing PRx reliability in TBI monitoring.

Cerebral autoregulation in paediatric and neonatal intensive care: A scoping review.

Deranged cerebral autoregulation (CA) is associated with worse outcome in adult brain injury. Strategies for monitoring CA and maintaining the brain at its 'best CA status' have been implemented, however, this approach has not yet developed for the paediatric population. This scoping review aims to find up-to-date evidence on CA assessment in children and neonates with a view to identify patient categories in which CA has been measured so far, CA monitoring methods and its relationship with clinical outcome if any. A literature search was conducted for studies published within 31st December 2022 in 3 bibliographic databases. Out of 494 papers screened, this review includes 135 studies. Our literature search reveals evidence for CA measurement in the paediatric population across different diagnostic categories and age groups. The techniques adopted, indices and thresholds used to assess and define CA are heterogeneous. We discuss the relevance of available evidence for CA assessment in the paediatric population. However, due to small number of studies and heterogeneity of methods used, there is no conclusive evidence to support universal adoption of CA monitoring, technique, and methodology. This calls for further work to understand the clinical impact of CA monitoring in paediatric and neonatal intensive care.

Embracing uncertainty in cerebrospinal fluid dynamics: A Bayesian approach to analysing infusion studies.

Introduction: Cerebrospinal fluid (CSF) infusion test analysis allows recognizing and appropriately evaluating CSF dynamics in the context of normal pressure hydrocephalus (NPH), which is crucial for effective diagnosis and treatment. However, existing methodology possesses drawbacks that may compromise the precision and interpretation of CSF dynamics parameters. Research question: This study aims to circumvent these constraints by introducing an innovative analysis method grounded in Bayesian inference. Material and methods: A single-centre retrospective cohort study was conducted on 858 patients who underwent a computerized CSF infusion test between 2004 and 2020. We developed a Bayesian framework-based method for parameter estimation and compared the results to the current, gradient descent-based approach. We evaluated the accuracy and reliability of both methods by analysing erroneous prediction rates and curve fitting errors. Results: The Bayesian method surpasses the gradient descent approach, reflected in reduced inaccurate prediction rates and an improved goodness of model fit. On whole cohort level both techniques produced comparable results. However, the Bayesian method holds an added advantage by providing uncertainty intervals for each parameter. Sensitivity analysis revealed significance of the CSF production rate parameter and its interplay with other variables. The resistance to CSF outflow demonstrated excellent robustness. Discussion and conclusion: The proposed Bayesian approach offers a promising solution for improving robustness of CSF dynamics assessment in NPH, based on CSF infusion tests. Additional provision of the uncertainty measure for each diagnostic metric may perhaps help to explain occasional poor diagnostic performance of the test, offering a robust framework for improved understanding and management of NPH.

A Comprehensive Perspective on Intracranial Pressure Monitoring and Individualized Management in Neurocritical Care: Results of a Survey with Global Experts.

BACKGROUND: Numerous trials have addressed intracranial pressure (ICP) management in neurocritical care. However, identifying its harmful thresholds and controlling ICP remain challenging in terms of improving outcomes. Evidence suggests that an individualized approach is necessary for establishing tolerance limits for ICP, incorporating factors such as ICP waveform (ICPW) or pulse morphology along with additional data provided by other invasive (e.g., brain oximetry) and noninvasive monitoring (NIM) methods (e.g., transcranial Doppler, optic nerve sheath diameter ultrasound, and pupillometry). This study aims to assess current ICP monitoring practices among experienced clinicians and explore whether guidelines should incorporate ancillary parameters from NIM and ICPW in future updates. METHODS: We conducted a survey among experienced professionals involved in researching and managing patients with severe injury across low-middle-income countries (LMICs) and high-income countries (HICs). We sought their insights on ICP monitoring, particularly focusing on the impact of NIM and ICPW in various clinical scenarios. RESULTS: From October to December 2023, 109 professionals from the Americas and Europe participated in the survey, evenly distributed between LMIC and HIC. When ICP ranged from 22 to 25 mm Hg, 62.3% of respondents were open to considering additional information, such as ICPW and other monitoring techniques, before adjusting therapy intensity levels. Moreover, 77% of respondents were inclined to reassess patients with ICP in the 18-22 mm Hg range, potentially escalating therapy intensity levels with the support of ICPW and NIM. Differences emerged between LMIC and HIC participants, with more LMIC respondents preferring arterial blood pressure transducer leveling at the heart and endorsing the use of NIM techniques and ICPW as ancillary information. CONCLUSIONS: Experienced clinicians tend to personalize ICP management, emphasizing the importance of considering various monitoring techniques. ICPW and noninvasive techniques, particularly in LMIC settings, warrant further exploration and could potentially enhance individualized patient care. The study suggests updating guidelines to include these additional components for a more personalized approach to ICP management.

Transmission of slow waves in Masimo O3 near infrared spectroscopy measures.

Introduction: Cerebral autoregulation (CA) dysfunction is a key complication following brain injury. CA assessment using near-infrared spectroscopy (NIRS) offers a promising alternative to the current non-invasive standard, cerebral blood flow velocity (CBFV) measured with transcranial Doppler. Research question: Can autoregulatory slow waves (frequency range 0.005-0.05 Hz) associated with spontaneous and induced changes in ABP in healthy volunteers be detected by parameters measured with the Masimo O3 NIRS device? Methods: ABP, CBFV and Masimo O3 parameters were measured in 10 healthy volunteers at baseline and during ABP oscillations induced by squat/stand manoeuvres. Transmission of slow waves was assessed with power spectral density and coherence analysis in NIRS signals and compared to that of CBFV. Results: At baseline, slow waves were detected with sufficient power that substantially exceeded the signals' measurement resolution in all parameters except cerebral oxygen saturation. During ABP oscillations in the 0.033 Hz range (induced by squat/stand), the power of slow waves increased in all parameters in a similar pattern, with total (cHb) and oxygenated (O2Hb) haemoglobin concentrations most closely mirroring CBFV (median standardised power [first-third quartile], baseline vs squat/stand: CBFV 0.35 [0.28-0.42] vs 0.50 [0.45-0.62], O2Hb 0.47 [0.33-0.68] vs 0.61 [0.59-0.69]). Coherence with ABP increased for both CBFV and NIRS measures from low at baseline (<0.4) to high during induced changes (>0.8). Conclusion: Spontaneous fluctuations in ABP can be observed in analysed Masimo O3 metrics to a varying degree. The clinical utility of Masimo O3 signals in CA assessment requires further investigation in brain injury patients.

Cardiovascular and cerebrovascular effects of caffeine maintenance in preterm infants during the transitional period.

BACKGROUND AND AIM: Caffeine is routinely used for the prophylaxis of prematurity-related apnoeas. We aimed to evaluate the effect of caffeine maintenance on cardiovascular and cerebrovascular haemodynamics using a non-invasive multimodal monitoring in preterm infants during the transitional period. METHODS: Infants <32 weeks' gestational age (GA) were enrolled in this observational prospective study. The following parameters were recorded before and after the administration of caffeine citrate 5 mg/kg using near-infrared spectroscopy, pulse oximetry and electrical velocimetry: heart rate, cardiac output, stroke volume, cardiac contractility, systemic vascular resistance (SVR), perfusion index, peripheral and cerebral oxygenation, cerebral fractional oxygen extraction, correlation index between cerebral oxygenation and heart rate (TOHRx, marker of cerebrovascular reactivity). Multilevel mixed-effects linear models were used to assess the impact of caffeine and of relevant clinical covariates on each parameter. RESULTS: Seventy-seven infants (mean GA 29.3 ± 2.5 weeks, mean birthweight 1148 ± 353 g) were included. Caffeine administration was associated with increased SVR (B = 0.623, p = 0.004) and more negative TOHRx values (B = -0.036, p = 0.022), which suggest improved cerebrovascular reactivity. CONCLUSIONS: Caffeine administration at maintenance dosage during postnatal transition is associated with increased systemic vascular tone and improved cerebrovascular reactivity. A possible role for caffeine-mediated inhibition of adenosine receptors may be hypothesized. IMPACT: This study provides a thorough and comprehensive overview of multiple cerebrovascular and cardiovascular parameters, monitored non-invasively by combining near-infrared spectroscopy, electrical velocimetry and pulse oximetry, before and after the administration of caffeine at maintenance dosage in preterm infants during postnatal transition. Caffeine was associated with an improvement in cerebrovascular reactivity and with a slight but significant increase in systemic vascular resistance, with no additional effects on other cardiovascular and cerebrovascular parameters. Our results support the safety of caffeine treatment even during a phase at risk for haemodynamic instability such as postnatal transition and suggest potential beneficial effects on cerebral haemodynamics.

Pitfalls and possibilities of using Root SedLine for continuous assessment of EEG waveform-based metrics in intensive care research.

Objective.The Root SedLine device is used for continuous electroencephalography (cEEG)-based sedation monitoring in intensive care patients. The cEEG traces can be collected for further processing and calculation of relevant metrics not already provided. Depending on the device settings during acquisition, the acquired traces may be distorted by max/min value cropping or high digitization errors. We aimed to systematically assess the impact of these distortions on metrics used for clinical research in the field of neuromonitoring.Approach.A 16 h cEEG acquired using the Root SedLine device at the optimal screen settings was analyzed. Cropping and digitization error effects were simulated by consecutive reduction of the maximum cEEG amplitude by 2µV or by reducing the vertical resolution. Metrics were calculated within ICM+ using minute-by-minute data, including the total power, alpha delta ratio (ADR), and 95% spectral edge frequency. Data were analyzed by creating violin- or box-plots.Main Results.Cropping led to a continuous reduction in total and band power, leading to corresponding changes in variability thereof. The relative power and ADR were less affected. Changes in resolution led to relevant changes. While the total power and power of low frequencies were rather stable, the power of higher frequencies increased with reducing resolution.Significance.Care must be taken when acquiring and analyzing cEEG waveforms from Root SedLine for clinical research. To retrieve good quality metrics, the screen settings must be kept within the central vertical scale, while pre-processing techniques must be applied to exclude unacceptable periods.

Predicting outcome after aneurysmal subarachnoid hemorrhage by exploitation of signal complexity: a prospective two-center cohort study.

BACKGROUND: Signal complexity (i.e. entropy) describes the level of order within a system. Low physiological signal complexity predicts unfavorable outcome in a variety of diseases and is assumed to reflect increased rigidity of the cardio/cerebrovascular system leading to (or reflecting) autoregulation failure. Aneurysmal subarachnoid hemorrhage (aSAH) is followed by a cascade of complex systemic and cerebral sequelae. In aSAH, the value of entropy has not been established yet. METHODS: aSAH patients from 2 prospective cohorts (Zurich-derivation cohort, Aachen-validation cohort) were included. Multiscale Entropy (MSE) was estimated for arterial blood pressure, intracranial pressure, heart rate, and their derivatives, and compared to dichotomized (1-4 vs. 5-8) or ordinal outcome (GOSE-extended Glasgow Outcome Scale) at 12 months using uni- and multivariable (adjusted for age, World Federation of Neurological Surgeons grade, modified Fisher (mFisher) grade, delayed cerebral infarction), and ordinal methods (proportional odds logistic regression/sliding dichotomy). The multivariable logistic regression models were validated internally using bootstrapping and externally by assessing the calibration and discrimination. RESULTS: A total of 330 (derivation: 241, validation: 89) aSAH patients were analyzed. Decreasing MSE was associated with a higher likelihood of unfavorable outcome independent of covariates and analysis method. The multivariable adjusted logistic regression models were well calibrated and only showed a slight decrease in discrimination when assessed in the validation cohort. The ordinal analysis revealed its effect to be linear. MSE remained valid when adjusting the outcome definition against the initial severity. CONCLUSIONS: MSE metrics and thereby complexity of physiological signals are independent, internally and externally valid predictors of 12-month outcome. Incorporating high-frequency physiological data as part of clinical outcome prediction may enable precise, individualized outcome prediction. The results of this study warrant further investigation into the cause of the resulting complexity as well as its association to important and potentially preventable complications including vasospasm and delayed cerebral ischemia.

Exploration of uncertainty of PRx time trends.

Introduction: PRx can be used as surrogate measure of Cerebral Autoregulation (CA) in traumatic brain injury (TBI) patients. PRx can provide means for individualising cerebral perfusion pressure (CPP) targets, such as CPPopt. However, a recent Delphi consensus of clinicians concluded that consensus could not be reached on the accuracy, reliability, and validation of any current CA assessment method. Research question: We aimed to quantify the short-term uncertainty of PRx time-trends and to relate this to other physiological measurements. Material and methods: Intracranial pressure (ICP), arterial blood pressure (ABP), end-tidal CO2 (EtCO2) high-resolution recordings of 911 TBI patients were processed with ICM + software. Hourly values of metrics that describe the variability within modalities derived from ABP, ICP and EtCO2, were calculated for the first 24h of neuromonitoring. Generalized additive models were used to describe the time trend of the variability in PRx. Linear correlations were studied for describing the relationship between PRx variability and the other physiological modalities. Results: The time profile of variability of PRx decreases over the first 12h and was higher for average PRx ∼0. Increased variability of PRx was not linearly linked with average ABP, ICP, or CPP. For coherence between slow waves of ABP and ICP >0.7, the variability in PRx decreased (R = -0.47, p < 0.001). Discussion and conclusion: PRx is a highly variable parameter. PRx short-term dispersion was not related to average ICP, ABP or CPP. The determinants of uncertainty of PRx should be investigated to improve reliability of individualised CA assessment in TBI patients.

Association between EEG metrics and continuous cerebrovascular autoregulation assessment: a scoping review.

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

Visualization of Cerebral Pressure Autoregulatory Insults in Traumatic Brain Injury.

OBJECTIVES: The first aim was to investigate the combined effect of insult intensity and duration of the pressure reactivity index (PRx) and deviation from the autoregulatory cerebral perfusion pressure target (∆CPPopt = actual CPP - optimal CPP [CPPopt]) on outcome in traumatic brain injury. The second aim was to determine if PRx influenced the association between intracranial pressure (ICP), CPP, and ∆CPPopt with outcome. DESIGN: Observational cohort study. SETTING: Neurocritical care unit, Cambridge, United Kingdom. PATIENTS: Five hundred fifty-three traumatic brain injury patients with ICP and arterial blood pressure monitoring and 6-month outcome data (Glasgow Outcome Scale [GOS]). INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: The insult intensity (mm Hg or PRx coefficient) and duration (minutes) of ICP, PRx, CPP, and ∆CPPopt were correlated with GOS and visualized in heatmaps. In these plots, there was a transition from favorable to unfavorable outcome when PRx remained positive for 30 minutes and this was also the case for shorter durations when the intensity was higher. In a similar plot of ∆CPPopt, there was a gradual transition from favorable to unfavorable outcome when ∆CPPopt went below -5 mm Hg for 30-minute episodes of time and for shorter durations for more negative ∆CPPopt. Furthermore, the percentage of monitoring time with certain combinations of PRx with ICP, CPP, and ∆CPPopt were correlated with GOS and visualized in heatmaps. In the combined PRx/ICP heatmap, ICP above 20 mm Hg together with PRx above 0 correlated with unfavorable outcome. In a PRx/CPP heatmap, CPP below 70 mm Hg together with PRx above 0.2-0.4 correlated with unfavorable outcome. In the PRx-/∆CPPopt heatmap, ∆CPPopt below 0 together with PRx above 0.2-0.4 correlated with unfavorable outcome. CONCLUSIONS: Higher intensities for longer durations of positive PRx and negative ∆CPPopt correlated with worse outcome. Elevated ICP, low CPP, and negative ∆CPPopt were particularly associated with worse outcomes when the cerebral pressure autoregulation was concurrently impaired.

Red solid line: Patterns of terminal loss of cerebrovascular reactivity at the bedside.

Introduction: Continuous monitoring of the pressure reactivity index (PRx) provides an estimation of dynamic cerebral autoregulation (CA) at the bedside in traumatic brain injury (TBI) patients. Visualising the time-trend of PRx with a risk bar chart in ICM + software at the bedside allows for better real-time interpretability of the autoregulation status. When PRx>0.3 is sustained for long periods, typically of at least half an hour, the bar shows a pattern called "red solid line" (RSL). RSL was previously described to precede refractory intracranial hypertension and brain death. Research question: We aimed to describe pathophysiological changes in measured signals/parameters during RSL. Material and methods: Observation of time-trends of PRx, intracranial pressure, cerebral perfusion pressure, brain oxygenation and compensatory reserve of TBI patients with RSL. Results: Three pathophysiological patterns were identified: RSL precedes intracranial hypertension, RSL is preceded by intracranial hypertension, or RSL is preceded by brain hypoperfusion. In all cases, RSL was followed by death and the RSL onset was between 1 h and 1 day before the terminal event. Discussion and conclusion: RSL precedes death in intensive care and could represent a marker for terminal clinical deterioration in TBI patients. These findings warrant further investigations in larger cohorts to characterise pathophysiological mechanisms underlying the RSL pattern and whether RSL has a significant relationship with outcome after TBI.

Mathematical modelling of cerebral haemodynamics and their effects on ICP.

Introduction: Electrical-equivalence mathematical models that integrate vascular and cerebrospinal fluid (CSF) compartments perform well in simulations of dynamic cerebrovascular variations and their transient effects on intracranial pressure (ICP). However, ICP changes due to sustained vascular diameter changes have not been comprehensively examined. We hypothesise that changes in cerebrovascular resistance (CVR) alter the resistance of the bulk flow of interstitial fluid (ISF). Research question: We hypothesise that changes in CVR alter the resistance of the bulk flow of ISF, thus allowing simulations of ICP in response to sustained vascular diameter changes. Material and methods: A lumped parameter model with vascular and CSF compartments was constructed and converted into an electrical analogue. The flow and pressure responses to transient hyperaemic response test (THRT) and CSF infusion test (IT) were observed. Arterial blood pressure (ABP) was manipulated to simulate ICP plateau waves. The experiments were repeated with a modified model that included the ISF compartment. Results: Simulations of the THRT produced identical cerebral blood flow (CBF) responses. ICP generated by the new model reacted in a similar manner as the original model during ITs. Plateau pressure reached during ITs was however higher in the ISF model. Only the latter was successful in simulating the onset of ICP plateau waves in response to selective blood pressure manipulations. Discussion and conclusion: Our simulations highlighted the importance of including the ISF compartment, which provides mechanism explaining sustained haemodynamic influences on ICP. Consideration of such interactions enables accurate simulations of the cerebrovascular effects on ICP.

The Effect of Recruitment Maneuvers on Cerebrovascular Dynamics and Right Ventricular Function in Patients with Acute Brain Injury: A Single-Center Prospective Study.

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 (rSO2). 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 O2 = 4 mm Hg; p = 0.001) and unchanged carbon dioxide levels, rSO2 marginally decreased (ΔrSO2 = -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.

Cerebral autoregulation derived blood pressure targets in elective neurosurgery.

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 O2 saturation-rSO2) could allow to individualise the management of ABP to preserve CA. We aimed to explore a continuous automated assessment of ABPOPT (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. ABPBASELINE was the mean of 3 pre-operative non-invasive measurements. ABP and rSO2 waveforms were processed to estimate COx-derived ABPOPT and LLA trend-lines. We assessed: availability (number of patients where ABPOPT/LLA were available); time required to achieve first values; differences between ABPOPT/LLA and ABP. ABPOPT 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 ABPOPT and LLA respectively. Median ABPOPT [75 (69-84)] was lower than ABPBASELINE [90 (84-95)] (p < 0.001, Mann-U test). Patients spent 72 (56-86) % of recorded time with ABP above or below ABPOPT ± 5 mmHg. ABPOPT 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.

Clinical descriptors of disease trajectories in patients with traumatic brain injury in the intensive care unit (CENTER-TBI): a multicentre observational cohort study.

BACKGROUND: Patients with traumatic brain injury are a heterogeneous population, and the most severely injured individuals are often treated in an intensive care unit (ICU). The primary injury at impact, and the harmful secondary events that can occur during the first week of the ICU stay, will affect outcome in this vulnerable group of patients. We aimed to identify clinical variables that might distinguish disease trajectories among patients with traumatic brain injury admitted to the ICU. METHODS: We used data from the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) prospective observational cohort study. We included patients aged 18 years or older with traumatic brain injury who were admitted to the ICU at one of the 65 CENTER-TBI participating centres, which range from large academic hospitals to small rural hospitals. For every patient, we obtained pre-injury data and injury features, clinical characteristics on admission, demographics, physiological parameters, laboratory features, brain biomarkers (ubiquitin carboxy-terminal hydrolase L1 [UCH-L1], S100 calcium-binding protein B [S100B], tau, neurofilament light [NFL], glial fibrillary acidic protein [GFAP], and neuron-specific enolase [NSE]), and information about intracranial pressure lowering treatments during the first 7 days of ICU stay. To identify clinical variables that might distinguish disease trajectories, we applied a novel clustering method to these data, which was based on a mixture of probabilistic graph models with a Markov chain extension. The relation of clusters to the extended Glasgow Outcome Scale (GOS-E) was investigated. FINDINGS: Between Dec 19, 2014, and Dec 17, 2017, 4509 patients with traumatic brain injury were recruited into the CENTER-TBI core dataset, of whom 1728 were eligible for this analysis. Glucose variation (defined as the difference between daily maximum and minimum glucose concentrations) and brain biomarkers (S100B, NSE, NFL, tau, UCH-L1, and GFAP) were consistently found to be the main clinical descriptors of disease trajectories (ie, the leading variables contributing to the distinguishing clusters) in patients with traumatic brain injury in the ICU. The disease trajectory cluster to which a patient was assigned in a model was analysed as a predictor together with variables from the IMPACT model, and prediction of both mortality and unfavourable outcome (dichotomised GOS-E ≤4) was improved. INTERPRETATION: First-day ICU admission data are not the only clinical descriptors of disease trajectories in patients with traumatic brain injury. By analysing temporal variables in our study, variation of glucose was identified as the most important clinical descriptor that might distinguish disease trajectories in the ICU, which should direct further research. Biomarkers of brain injury (S100B, NSE, NFL, tau, UCH-L1, and GFAP) were also top clinical descriptors over time, suggesting they might be important in future clinical practice. FUNDING: European Union 7th Framework program, Hannelore Kohl Stiftung, OneMind, Integra LifeSciences Corporation, and NeuroTrauma Sciences.

Cerebral autoregulation monitoring using the cerebral oximetry index after neonatal cardiac surgery: A single-center retrospective cohort study.

OBJECTIVE: To investigate whether cerebral autoregulation is impaired after neonatal cardiac surgery and whether changes in autoregulation metrics are associated with different congenital heart defects or the incidence of postoperative neurologic events. METHODS: This is a retrospective observational study of neonates undergoing monitoring during the first 72 hours after cardiac surgery. Archived data were processed to calculate the cerebral oximetry index (COx) and derived metrics. Acute neurologic events were identified by an electronic medical record review. The Skillings-Mack test and the Wilcoxon signed-rank test were used to analyze the evolution of autoregulation metrics over time; the Mann-Whitney U test was used for comparison between groups. RESULTS: We included 28 neonates, 7 (25%) with hypoplastic left heart syndrome and 21 (75%) with transposition of the great arteries. Overall, the median percentage of time spent with impaired autoregulation, defined as percentage of time with a COx >0.3, was 31.6% (interquartile range, 21.1%-38.3%). No differences in autoregulation metrics between different cardiac defects subgroups were observed. Seven patients (25%) experienced a postoperative acute neurologic event. Compared to the neonates without an acute neurologic event, those with an acute neurologic event had a higher COx (0.16 vs 0.07; P = .035), a higher percentage of time with a COx >0.3 (39.4% vs 29.2%; P = .017), and a higher percentage of time with a mean arterial pressure below the lower limit of autoregulation (13.3% vs 6.9%; P = .048). CONCLUSIONS: COx monitoring after cardiac surgery allowed for the detection of impaired cerebral autoregulation, which was more frequent in neonates with postoperative acute neurologic events.

Cerebral hemodynamic monitoring combined with infusion test in hydrocephalus.

Introduction: Disturbance in cerebrospinal fluid (CSF) circulation may overlap with abnormality of cerebral blood flow (CBF) in hydrocephalus. Transcranial Doppler (TCD) ultrasonography is a non-invasive technique able to assess CBF velocity (CBFv) dynamics in response to a controlled rise in ICP during CSF infusion tests. Research question: Which TCD-derived cerebral hemodynamic parameters change during controlled rise of ICP, and in which direction? Material and methods: Infusion tests combined with TCD monitoring and non-invasive monitoring of arterial blood pressure (ABP) were conducted in 65 hydrocephalic patients. TCD-based hemodynamic variables: spectral pulsatility index (sPI), compliance of CSF space (Ci), cerebral autoregulation index (Mx), critical closing pressure (CrCP), cerebrovascular wall tension (WT) and diastolic closing margin (DCM-distance between diastolic ABP and CrCP) were calculated retrospectively. Results: During the test ICP increased on average to 25 mm Hg (p < 0.0001), with a parallel decrease in cerebral perfusion pressure (CPP, p < 0.0003). The CBFv waveform changed, showing a rise in sPI (p < 0.0001). Ci decreased inversely proportional to a rise in ICP, and correlated well with changes of compliance calculated from the Marmarou model. CrCP increased in response to rising ICP (p < 0.001) while WT decreased (p < 0.002). DCM correlated with cerebrospinal elasticity (R = -0.31; p < 0.04). Cerebral autoregulation was worse in patients with normal CSF circulation, measured as resistance to CSF outflow (Rout): Pearson correlation between Mx and Rout was R = -0.41; p < 0.02. Conclusion: A controlled rise in ICP affects cerebral hemodynamics in a moderate manner. Parameters like cerebral autoregulation index or DCM correlate with CSF dynamics and may be considered as supplementary variables for the diagnosis of hydrocephalus.