A daily temperature rhythm in the human brain predicts survival after brain injury.

Patients undergo interventions to achieve a 'normal' brain temperature; a parameter that remains undefined for humans. The profound sensitivity of neuronal function to temperature implies the brain should be isothermal, but observations from patients and non-human primates suggest significant spatiotemporal variation. We aimed to determine the clinical relevance of brain temperature in patients by establishing how much it varies in healthy adults. We retrospectively screened data for all patients recruited to the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) High Resolution Intensive Care Unit Sub-Study. Only patients with direct brain temperature measurements and without targeted temperature management were included. To interpret patient analyses, we prospectively recruited 40 healthy adults (20 males, 20 females, 20-40 years) for brain thermometry using magnetic resonance spectroscopy. Participants were scanned in the morning, afternoon, and late evening of a single day. In patients (n = 114), brain temperature ranged from 32.6 to 42.3°C and mean brain temperature (38.5 ± 0.8°C) exceeded body temperature (37.5 ± 0.5°C, P < 0.0001). Of 100 patients eligible for brain temperature rhythm analysis, 25 displayed a daily rhythm, and the brain temperature range decreased in older patients (P = 0.018). In healthy participants, brain temperature ranged from 36.1 to 40.9°C; mean brain temperature (38.5 ± 0.4°C) exceeded oral temperature (36.0 ± 0.5°C) and was 0.36°C higher in luteal females relative to follicular females and males (P = 0.0006 and P < 0.0001, respectively). Temperature increased with age, most notably in deep brain regions (0.6°C over 20 years, P = 0.0002), and varied spatially by 2.41 ± 0.46°C with highest temperatures in the thalamus. Brain temperature varied by time of day, especially in deep regions (0.86°C, P = 0.0001), and was lowest at night. From the healthy data we built HEATWAVE-a 4D map of human brain temperature. Testing the clinical relevance of HEATWAVE in patients, we found that lack of a daily brain temperature rhythm increased the odds of death in intensive care 21-fold (P = 0.016), whilst absolute temperature maxima or minima did not predict outcome. A warmer mean brain temperature was associated with survival (P = 0.035), however, and ageing by 10 years increased the odds of death 11-fold (P = 0.0002). Human brain temperature is higher and varies more than previously assumed-by age, sex, menstrual cycle, brain region, and time of day. This has major implications for temperature monitoring and management, with daily brain temperature rhythmicity emerging as one of the strongest single predictors of survival after brain injury. We conclude that daily rhythmic brain temperature variation-not absolute brain temperature-is one way in which human brain physiology may be distinguished from pathophysiology.

Automatic Pulse Classification for Artefact Removal Using SAX Strings, a CENTER-TBI Study.

High-resolution, waveform-level data from bedside monitors carry important information about a patient's physiology but is also polluted with artefactual data. Manual mark-up is the standard practice for detecting and eliminating artefacts, but it is time-consuming, prone to errors, biased and not suitable for real-time processing.In this paper we present a novel automatic artefact detection technique based on a Symbolic Aggregate approXimation (SAX) technique which makes it possible to represent individual pulses as 'words'. It does that by coding each pulse with a specified number of letters (here six) from a predefined alphabet of characters (here six). The word is then fed to a support vector machine (SVM) and classified as artefactual or physiological.To define the universe of acceptable pulses, the arterial blood pressure from 50 patients was analysed, and acceptable pulses were manually chosen by looking at the average pulse that each 'word' generated. This was then used to train a SVM classifier. To test this algorithm, a dataset with a balanced ratio of clean and artefactual pulses was built, classified and independently evaluated by two observers achieving a sensitivity of 0.972 and 0.954 and a specificity of 0.837 and 0.837 respectively.

Python-Embedded Plugin Implementation in ICM+: Novel Tools for Neuromonitoring Time Series Analysis with Examples Using CENTER-TBI Datasets.

With the appearance of publicly available, high-resolution, physiological datasets in neurocritical care, like Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI), there is a growing need for tools that could be used by clinical researchers to interrogate this information-rich data. The ICM+ software is widely used for processing data acquired from bedside monitors. Considering the growing popularity of scripting simple-syntax programming languages like Python, particularly among clinical researchers, we have developed an interface in ICM+ that provides a streamlined way of adding Python scripting functionality to the ICM+ calculation engine. The new interface imposes certain requirements on the scripts and needs an accompanying descriptor file that tells ICM+ about the functions implemented, so that they become available to the end user in the same way as native ICM+ functions. ICM+ also now includes a tool that eases the creation of Python functions to be imported. The Python extension works very efficiently, and any user with some degree of experience in scripting can use it to enrich capabilities of ICM+. Depending on the data analysed and calculations performed, Python functions are 15-60% slower than built-in ICM+ functions, which is a more-than-acceptable trade-off for empowering ICM+ with the unlimited analytical freedom offered by extensive Python libraries.

Optimal Cerebral Perfusion Pressure Based on Intracranial Pressure-Derived Indices of Cerebrovascular Reactivity: Which One Is Better for Outcome Prediction in Moderate/Severe Traumatic Brain Injury?

Intracranial pressure (ICP)-derived indices of cerebrovascular reactivity (e.g., PRx, PAx, and RAC) have been developed to improve understanding of brain status from available neuromonitoring variables. These indices are moving correlation coefficients between slow-wave vasogenic fluctuations in ICP and arterial blood pressure. In this retrospective analysis of neuromonitoring data from 200 patients admitted with moderate/severe traumatic brain injury (TBI), we evaluate the predictive value of CPPopt based on these ICP-derived indices of cerebrovascular reactivity. Valid CPPopt values were obtained in 92.3% (PRx), 86.7% (PAX), and 84.6% (RAC) of the monitoring periods, respectively. In multivariate logistic analysis, a baseline model that includes age, sex, and admission Glasgow Coma Score had an area under the receiver operating curve of 0.762 (P < 0.0001) for dichotomous outcome prediction (dead vs. good recovery). When adding time/dose of CPP below CPPopt, all multivariate models (based on PRx, PAx, and RAC) predicted the dichotomous outcome measure, but additional value of the prediction was only significantly added by the PRx-based calculations of time spent with CPP below CPPopt and dose of CPP below CPPopt.

DeepClean: Self-Supervised Artefact Rejection for Intensive Care Waveform Data Using Deep Generative Learning.

Waveform physiological data are important in the treatment of critically ill patients in the intensive care unit. Such recordings are susceptible to artefacts, which must be removed before the data can be reused for alerting or reprocessed for other clinical or research purposes. Accurate removal of artefacts reduces bias and uncertainty in clinical assessment, as well as the false positive rate of ICU alarms, and is therefore a key component in providing optimal clinical care. In this work, we present DeepClean, a prototype self-supervised artefact detection system using a convolutional variational autoencoder deep neural network that avoids costly and painstaking manual annotation, requiring only easily obtained 'good' data for training. For a test case with invasive arterial blood pressure, we demonstrate that our algorithm can detect the presence of an artefact within a 10s sample of data with sensitivity and specificity around 90%. Furthermore, DeepClean was able to identify regions of artefacts within such samples with high accuracy, and we show that it significantly outperforms a baseline principal component analysis approach in both signal reconstruction and artefact detection. DeepClean learns a generative model and therefore may also be used for imputation of missing data.

Errors and Consequences of Inaccurate Estimation of Mean Blood Flow Velocity in Cerebral Arteries.

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.

Patient's Clinical Presentation and CPPopt Availability: Any Association?

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.

Optimal Cerebral Perfusion Pressure Assessed with a Multi-Window Weighted Approach Adapted for Prospective Use: A Validation Study.

BACKGROUND: Pressure reactivity index (PRx)-cerebral perfusion pressure (CPP) relationships over a given time period can be used to detect a value of CPP at which PRx shows the best autoregulation (optimal CPP, or CPPopt). Algorithms for continuous assessment of CPPopt in traumatic brain injury (TBI) patients reached the desired high yield with a multi-window approach (CPPopt_MA). However, the calculations were tested on retrospective manually cleaned datasets. Moreover, CPPopt false-positive values can be generated from non-physiological variations of intracranial pressure (ICP) and arterial blood pressure (ABP). Therefore, the algorithm robustness was improved, making it suitable for prospective bedside application (COGiTATE trial). OBJECTIVE: To validate the CPPopt revised algorithm in a large single-centre retrospective cohort of TBI patients. METHODS: 840 TBI patients were included. CPPopt yield, stability and ability to discriminate outcome groups were compared to CPPopt_MA and the Brain Trauma Foundation (BTF) guideline reference. RESULTS: CPPopt yield was lower than CPPopt_MA yield (85% and 90%, p < 0.001), but, importantly, with increased stability (p < 0.0001). The ∆(CPP-CPPopt) could distinguish the mortality and survival outcome (t = -6.7, p < 0.0001) with a statistical significance higher than the ∆CPP calculated with the guideline reference (CPP-60) (t = -4.5, p < 0.0001). CONCLUSION: This study validates, on a large cohort of patients, the new algorithm proposed for prospective use of CPPopt as a CPP target at bedside.

An Update on the COGiTATE Phase II Study: Feasibility and Safety of Targeting an Optimal Cerebral Perfusion Pressure as a Patient-Tailored Therapy in Severe Traumatic Brain Injury.

INTRODUCTION: Monitoring of cerebral autoregulation (CA) in patients with a traumatic brain injury (TBI) can provide an individual 'optimal' cerebral perfusion pressure (CPP) target (CPPopt) at which CA is best preserved. This potentially offers an individualized precision medicine approach. Retrospective data suggest that deviation of CPP from CPPopt is associated with poor outcomes. We are prospectively assessing the feasibility and safety of this approach in the COGiTATE [CPPopt Guided Therapy: Assessment of Target Effectiveness] study. Its primary objective is to demonstrate the feasibility of individualizing CPP at CPPopt in TBI patients. The secondary objectives are to investigate the safety and physiological effects of this strategy. METHODS: The COGiTATE study has included patients in four European hospitals in Cambridge, Leuven, Nijmegen, and Maastricht (coordinating centre). Patients with severe TBI requiring intracranial pressure (ICP)-directed therapy are allocated into one of two groups. In the intervention group, CPPopt is calculated using a published (modified) algorithm. In the control group, the CPP target recommended in the Brain Trauma Foundation guidelines (CPP 60-70 mmHg) is used. RESULTS: Patient recruitment started in February 2018 and will continue until 60 patients have been studied. Fifty-one patients (85% of the intended total) have been recruited in October 2019. The first results are expected early 2021. CONCLUSION: This prospective evaluation of the feasibility, safety and physiological implications of autoregulation-guided CPP management is providing evidence that will be useful in the design of a future phase III study in severe TBI patients.

Evaluation of the relationship between slow-waves of intracranial pressure, mean arterial pressure and brain tissue oxygen in TBI: a CENTER-TBI exploratory analysis.

Brain tissue oxygen (PbtO2) monitoring in traumatic brain injury (TBI) has demonstrated strong associations with global outcome. Additionally, PbtO2 signals have been used to derive indices thought to be associated with cerebrovascular reactivity in TBI. However, their true relationship to slow-wave vasogenic fluctuations associated with cerebral autoregulation remains unclear. The goal of this study was to investigate the relationship between slow-wave fluctuations of intracranial pressure (ICP), mean arterial pressure (MAP) and PbtO2 over time. Using the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) high resolution ICU sub-study cohort, we evaluated those patients with recorded high-frequency digital intra-parenchymal ICP and PbtO2 monitoring data of a minimum of 6 h in duration. Digital physiologic signals were processed for ICP, MAP, and PbtO2 slow-waves using a moving average filter to decimate the high-frequency signal. The first 5 days of recording were analyzed. The relationship between ICP, MAP and PbtO2 slow-waves over time were assessed using autoregressive integrative moving average (ARIMA) and vector autoregressive integrative moving average (VARIMA) modelling, as well as Granger causality testing. A total of 47 patients were included. The ARIMA structure of ICP and MAP were similar in time, where PbtO2 displayed different optimal structure. VARIMA modelling and IRF plots confirmed the strong directional relationship between MAP and ICP, demonstrating an ICP response to MAP impulse. PbtO2 slow-waves, however, failed to demonstrate a definite response to ICP and MAP slow-wave impulses. These results raise questions as to the utility of PbtO2 in the derivation of cerebrovascular reactivity measures in TBI. There is a reproducible relationship between slow-wave fluctuations of ICP and MAP, as demonstrated across various time-series analytic techniques. PbtO2 does not appear to reliably respond in time to slow-wave fluctuations in MAP, as demonstrated on various VARIMA models across all patients. These findings suggest that PbtO2 should not be utilized in the derivation of cerebrovascular reactivity metrics in TBI, as it does not appear to be responsive to changes in MAP in the slow-waves. These findings corroborate previous results regarding PbtO2 based cerebrovascular reactivity indices.

Descriptive analysis of low versus elevated intracranial pressure on cerebral physiology in adult traumatic brain injury: a CENTER-TBI exploratory study.

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 (PbtO2), 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, PbtO2, 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.

Univariate comparison of performance of different cerebrovascular reactivity indices for outcome association in adult TBI: a CENTER-TBI study.

BACKGROUND: Monitoring cerebrovascular reactivity in adult traumatic brain injury (TBI) has been linked to global patient outcome. Three intra-cranial pressure (ICP)-derived indices have been described. It is unknown which index is superior for outcome association in TBI outside previous single-center evaluations. The goal of this study is to evaluate indices for 6- to 12-month outcome association using uniform data harvested in multiple centers. METHODS: Using the prospectively collected data from the Collaborative European NeuroTrauma Effectiveness Research in TBI (CENTER-TBI) study, the following indices of cerebrovascular reactivity were derived: PRx (correlation between ICP and mean arterial pressure (MAP)), PAx (correlation between pulse amplitude of ICP (AMP) and MAP), and RAC (correlation between AMP and cerebral perfusion pressure (CPP)). Univariate logistic regression models were created to assess the association between vascular reactivity indices with global dichotomized outcome at 6 to 12 months, as assessed by Glasgow Outcome Score-Extended (GOSE). Models were compared via area under the receiver operating curve (AUC) and Delong's test. RESULTS: Two separate patient groups from this cohort were assessed: the total population with available data (n = 204) and only those without decompressive craniectomy (n = 159), with identical results. PRx, PAx, and RAC perform similar in outcome association for both dichotomized outcomes, alive/dead and favorable/unfavorable, with RAC trending towards higher AUC values. There were statistically higher mean values for the index, % time above threshold, and hourly dose above threshold for each of PRx, PAx, and RAC in those patients with poor outcomes. CONCLUSIONS: PRx, PAx, and RAC appear similar in their associations with 6- to 12-month outcome in moderate/severe adult TBI, with RAC showing tendency to achieve stronger associations. Further work is required to determine the role for each of these cerebrovascular indices in monitoring of TBI patients.

Correction to: Univariate comparison of performance of different cerebrovascular reactivity indices for outcome association in adult TBI: a CENTER-TBI study.

Incorrect family name of Nino Stocchetti.

Compensatory-reserve-weighted intracranial pressure versus intracranial pressure for outcome association in adult traumatic brain injury: a CENTER-TBI validation study.

BACKGROUND: Compensatory-reserve-weighted intracranial pressure (wICP) has recently been suggested as a supplementary measure of intracranial pressure (ICP) in adult traumatic brain injury (TBI), with a single-center study suggesting an association with mortality at 6 months. No multi-center studies exist to validate this relationship. The goal was to compare wICP to ICP for association with outcome in a multi-center TBI cohort. METHODS: Using the Collaborative European Neuro Trauma Effectiveness Research in TBI (CENTER-TBI) high-resolution intensive care unit (ICU) cohort, we derived ICP and wICP (calculated as wICP = (1 - RAP) × ICP; where RAP is the compensatory reserve index derived from the moving correlation between pulse amplitude of ICP and ICP). Various univariate logistic regression models were created comparing ICP and wICP to dichotomized outcome at 6 to 12 months, based on Glasgow Outcome Score-Extended (GOSE) (alive/dead-GOSE ≥ 2/GOSE = 1; favorable/unfavorable-GOSE 5 to 8/GOSE 1 to 4, respectively). Models were compared using area under the receiver operating curves (AUC) and p values. RESULTS: wICP displayed higher AUC compared to ICP on univariate regression for alive/dead outcome compared to mean ICP (AUC 0.712, 95% CI 0.615-0.810, p = 0.0002, and AUC 0.642, 95% CI 0.538-746, p < 0.0001, respectively; no significant difference on Delong's test), and for favorable/unfavorable outcome (AUC 0.627, 95% CI 0.548-0.705, p = 0.015, and AUC 0.495, 95% CI 0.413-0.577, p = 0.059; significantly different using Delong's test p = 0.002), with lower wICP values associated with improved outcomes (p < 0.05 for both). These relationships on univariate analysis held true even when comparing the wICP models with those containing both ICP and RAP integrated area under the curve over time (p < 0.05 for all via Delong's test). CONCLUSIONS: Compensatory-reserve-weighted ICP displays superior outcome association for both alive/dead and favorable/unfavorable dichotomized outcomes in adult TBI, through univariate analysis. Lower wICP is associated with better global outcomes. The results of this study provide multi-center validation of those seen in a previous single-center study.

Cerebrovascular reactivity is not associated with therapeutic intensity in adult traumatic brain injury: a CENTER-TBI analysis.

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.

Wavelet pressure reactivity index: a validation study.

KEY POINTS: The brain is vulnerable to damage from too little or too much blood flow. A physiological mechanism termed cerebral autoregulation (CA) exists to maintain stable blood flow even if cerebral perfusion pressure (CPP) is changing. A robust method for assessing CA is not yet available. There are still some problems with the traditional measure, the pressure reactivity index (PRx). We introduce a new method, the wavelet transform method (wPRx), to assess CA using data from two sets of controlled hypotension experiments in piglets: one set had artificially manipulated arterial blood pressure (ABP) oscillations; the other group were spontaneous ABP waves. A significant linear relationship was found between wPRx and PRx in both groups, with wPRx providing a more stable result for the spontaneous waves. Although both methods showed similar accuracy in distinguishing intact and impaired CA, it seems that wPRx tends to perform better than PRx, although not significantly so. ABSTRACT: We present a novel method to monitor cerebral autoregulation (CA) using the wavelet transform (WT). The new method is validated against the pressure reactivity index (PRx) in two piglet experiments with controlled hypotension. The first experiment (n = 12) had controlled haemorrhage with artificial stationary arterial blood pressure (ABP) and intracranial pressure (ICP) oscillations induced by sinusoidal slow changes in positive end-expiratory pressure ('PEEP group'). The second experiment (n = 17) had venous balloon inflation during spontaneous, non-stationary ABP and ICP oscillations ('non-PEEP group'). The wavelet transform phase shift (WTP) between ABP and ICP was calculated in the frequency range 0.0067-0.05 Hz. Wavelet semblance, the cosine of WTP, was used to make the values comparable to PRx, and the new index was termed wavelet pressure reactivity index (wPRx). The traditional PRx, the running correlation coefficient between ABP and ICP, was calculated. The result showed a significant linear relationship between wPRx and PRx in the PEEP group (R = 0.88) and non-PEEP group (R = 0.56). In the non-PEEP group, wPRx showed better performance than PRx in distinguishing cerebral perfusion pressure (CPP) above and below the lower limit of autoregulation (LLA). When CPP was decreased below LLA, wPRx increased from 0.43 ± 0.28 to 0.69 ± 0.12 (P = 0.003) while PRx increased from 0.07 ± 0.21 to 0.27 ± 0.37 (P = 0.04). Moreover, wPRx provided a more stable result than PRx (SD of PRx was 0.40 ± 0.07, and SD of wPRx was 0.28 ± 0.11, P = 0.001). Assessment of CA using wavelet-derived phase shift between ABP and ICP is feasible.

HDF5-Based Data Format for Archiving Complex Neuro-monitoring Data in Traumatic Brain Injury Patients.

OBJECTIVES: Modern neuro-critical care units generate high volumes of data. These data originate from a multitude of devices in various formats and levels of granularity. We present a new data format intended to store these data in an ordered and homogenous way. MATERIAL AND METHODS: The adopted data format was based on the hierarchical model, HDF5, which is capable of dealing with a mixture of small and very large datasets with equal ease. It is possible to access and manipulate individual data elements directly within a single file, and this is extensible and versatile. RESULTS: The file structure that was agreed divided the patient data into four different groups: 'Annotations' for clinical events and sporadic observations, 'Numerics' for all the low-frequency data, 'Waves' for all the high-frequency data and 'Summaries' for the trend data and calculated parameters. The addition of attributes to every group and dataset makes the file self-described. More than 200 files have been successfully collected and stored using this format. CONCLUSION: The new file format was implemented in ICM+ software and validated as part of a collaboration with participating centres across Europe.

Pre-hospital Predictors of Impaired ICP Trends in Continuous Monitoring of Paediatric Traumatic Brain Injury Patients.

OBJECTIVE: Although secondary insults such as raised intracranial pressure (ICP) or cardiovascular compromise strongly contribute to morbidity, a growing interest can be noticed in how the pre-hospital management can affect outcomes after traumatic brain injury (TBI). The objective of this study was to determine whether pre-hospital co-morbidity has influence on patterns of continuously measured waveforms of intracranial physiology after paediatric TBI. MATERIALS AND METHODS: Thirty-nine patients (mean age, 10 years; range, 0.5-15) admitted between 2002 and 2015 were used for the current analysis. Pre-hospital motor score, pupil reactivity, pre-hospital hypoxia (SpO2 < 90%) and hypotension (mean arterial pressure < 70 mmHg) were documented. ICP and arterial blood pressure (ABP) were monitored continuously with an intraparenchymal microtransducer and an indwelling arterial line. Pressure monitors were connected to bedside computers running ICM+ software. Pressure reactivity was determined as the moving correlation between 30 10-s averages of ABP and ICP (PRx). The mean ICP and PRx were calculated for the whole monitoring period for each patient. RESULTS: Those with pre-hospital hypotension were susceptible to higher ICP [20 (IQR 8) vs 13 (IQR 6) mmHg; p = 0.01] and more frequent ICP plateau waves [median = 0 (IQR 1), median = 4 (IQR 9); p = 0.001], despite having similar MAP, CPP and PRx during monitoring. Those with unreactive pupils tended to have higher ICP than those with reactive pupils (18 vs 14 mmHg, p = 0.08). Pre-hospital hypoxia, motor score and pupillary reactivity were not related to subsequent monitored intracranial or systemic physiology. CONCLUSION: In paediatric TBI, pre-hospital hypotension is associated with increased ICP in the intensive care unit.

Computed Tomography Indicators of Deranged Intracranial Physiology in Paediatric Traumatic Brain Injury.

OBJECTIVE: Computed tomography (CT) of the brain can allow rapid assessment of intracranial pathology after traumatic brain injury (TBI). Frequently in paediatric TBI, CT imaging can fail to display the classical features of severe brain injury with raised intracranial pressure. The objective of this study was to determine early CT brain features that influence intracranial or systemic physiological trends following paediatric TBI. MATERIALS AND METHODS: Thirty-three patients (mean age, 10 years; range, 0.5-16) admitted between 2002 and 2015 were used for the current analysis. Presence of petechial haemorrhages, basal cistern compression, subarachnoid blood, midline shift and extra-axial masses on the initial trauma CT head were assessed. ICP and arterial blood pressure (ABP) were then monitored continuously with an intraparenchymal microtransducer and an indwelling arterial line. Pressure monitors were connected to bedside computers running ICM+ software. Pressure reactivity was determined as the moving correlation between 30, 10-s averages of ABP and ICP (PRx). The mean ICP, ABP, cerebral perfusion pressure (CPP; ABP minus ICP) and PRx were calculated for the whole monitoring period for each patient. RESULTS: The presence of subarachnoid blood was related to higher ICP, higher ABP and a trend toward higher PRx. Smaller basal cisterns were related to increased ICP (R = -0.42, p = 0.02), impaired PRx (R = -0.5, p = 0.003). The presence of an extra-axial mass was associated with deranged PRx (-0.02 vs. 0.41, p = 0.003) and a trend toward higher ICP (14 vs. 40, p = 0.07). Interestingly the degree of midline shift was not related to ICP or PRx. CONCLUSIONS: The size of the basal cisterns, the presence of subarachnoid blood or an extra-axial mass are all related to disturbed ICP and pressure reactivity in this paediatric TBI cohort. Patients with these features are ideal candidates for invasive multimodal monitoring.

Non-invasive Intracranial Pressure Assessment in Brain Injured Patients Using Ultrasound-Based Methods.

BACKGROUND: Non-invasive measurement of intracranial pressure (ICP) can be invaluable in the management of critically ill patients. Invasive measurement of ICP remains the "gold standard" and should be performed when clinical indications are met, but it is invasive and brings some risks. In this project, we aim to validate the non-invasive ICP (nICP) assessment models based on arterious and venous transcranial Doppler ultrasonography (TCD) and optic nerve sheath diameter (ONSD). METHODS: We included brain injured patients requiring invasive ICP monitoring (intraparenchymal or intraventricular). We assessed the concordance between ICP measured non-invasively with arterious [flow velocity diastolic formula (ICPFVd) and pulsatility index (PI)], venous TCD (vPI) and ICP derived from ONSD (nICPONSD) compared to invasive ICP measurement. RESULTS: Linear regression showed a positive relationship between nICP and ICP for all the methods, except PIv. ICPONSD showed the strongest correlation with invasive ICP (r = 0.61) compared to the other methods (ICPFVd, r = 0.26, p value = 0.0015; PI, r = 0.19, p value = 0.02, vPI, r = 0.056, p value = 0.510). The ability to predict intracranial hypertension was highest for ICPONSD (AUC = 0.91; 95% CI, 0.85-0.97 at ICP > 20 mmHg), with a sensitivity and specificity of 85%, followed by ICPFVd (AUC = 0.67; 95% CI, 0.54-0.79). CONCLUSIONS: Our results demonstrate that among the non-invasive methods studied, ONSD showed the best accuracy in the detection of ICP.