Publications by authors named "Peter Smielewski"

285 Publications

Clinical determinants of cerebrovascular reactivity in very preterm infants during the transitional period.

Pediatr Res 2022 May 5. Epub 2022 May 5.

Neonatal Intensive Care Unit, IRCCS S. Orsola-Malpighi Hospital, Bologna, Italy.

Background: Preterm infants are at enhanced risk of brain injury due to altered cerebral haemodynamics during postnatal transition. This observational study aimed to assess the clinical determinants of transitional cerebrovascular reactivity and its association with intraventricular haemorrhage (IVH).

Methods: Preterm infants <32 weeks underwent continuous monitoring of cerebral oxygenation and heart rate over the first 72 h after birth. Serial cranial and cardiac ultrasound assessments were performed to evaluate the ductal status and to diagnose IVH onset. The moving correlation coefficient between cerebral oxygenation and heart rate (TOHRx) was calculated. Linear mixed-effect models were used to analyse the impact of relevant clinical variables on TOHRx. The association between TOHRx and IVH development was also assessed.

Results: Seventy-seven infants were included. A haemodynamically significant patent ductus arteriosus (hsPDA) (β = 0.044, 95% CI: 0.007-0.081) and ongoing dopamine treatment (β = 0.096, 95% CI: 0.032-0.159) were associated with increasing TOHRx, indicating impaired cerebrovascular reactivity. A significant association between TOHRx, mean arterial blood pressure (β = -0.004, 95% CI: -0.007, -0.001) and CRIB-II score (β = 0.007, 95% CI: 0.001-0.015) was also observed. TOHRx was significantly higher in infants developing high-grade IVH compared to those without IVH.

Conclusions: Dopamine treatment, low blood pressure, hsPDA and high CRIB-II are associated with impaired cerebrovascular reactivity during postnatal transition, with potential implications on IVH development.

Impact: The correlation coefficient between cerebral oxygenation and heart rate (TOHRx) provides a non-invasive estimation of cerebrovascular reactivity, whose failure has a potential pathogenic role in the development of IVH in preterm infants. This study shows that cerebrovascular reactivity during the transitional period improves over time and is affected by specific clinical and therapeutic factors, whose knowledge could support the development of individualized neuroprotective strategies in at-risk preterm infants. The evidence of increased TOHRx in infants developing high-grade compared to low-grade or no IVH during the transitional period further supports the role of impaired cerebrovascular reactivity in IVH pathophysiology.
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http://dx.doi.org/10.1038/s41390-022-02090-zDOI Listing
May 2022

Feasibility of non-invasive neuromonitoring in general intensive care patients using a multi-parameter transcranial Doppler approach.

J Clin Monit Comput 2022 Mar 1. Epub 2022 Mar 1.

Department of Neurology and Neurocritical Care Unit, Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation, Cambridge, United Kingdom.

Purpose: To assess the feasibility of Transcranial Doppler ultrasonography (TCD) neuromonitoring in a general intensive care environment, in the prognosis and outcome prediction of patients who are in coma due to a variety of critical conditions.

Methods: The prospective trial was performed between March 2017 and March 2019 Addenbrooke's Hospital, Cambridge, UK. Forty adult patients who failed to awake appropriately after resuscitation from cardiac arrest or were in coma due to conditions such as meningitis, seizures, sepsis, metabolic encephalopathies, overdose, multiorgan failure or transplant were eligible for inclusion. Gathered data included admission diagnosis, duration of ventilation, length of stay in the ICU, length of stay in hospital, discharge status using Cerebral Performance Categories (CPC). All patients received intermittent extended TCD monitoring following inclusion in the study. Parameters of interest included TCD-based indices of cerebral autoregulation, non-invasive intracranial pressure, autonomic system parameters (based on heart rate variability), critical closing pressure, the cerebrovascular time constant and indices describing the shape of the TCD pulse waveform.

Results: Thirty-seven patients were included in the final analysis, with 21 patients classified as good outcome (CPC 1-2) and 16 as poor neurological outcomes (CPC 3-5). Three patients were excluded due to inadequacies identified in the TCD acquisition. The results indicated that irrespective of the primary diagnosis, non-survivors had significantly disturbed cerebral autoregulation, a shorter cerebrovascular time constant and a more distorted TCD pulse waveform (all p<0.05).

Conclusions: Preliminary results from the trial indicate that multi-parameter TCD neuromonitoring increases outcome-predictive power and TCD-based indices can be applied to general intensive care monitoring.
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http://dx.doi.org/10.1007/s10877-022-00829-xDOI Listing
March 2022

Relationship Between Baroreflex and Cerebral Autoregulation in Patients With Cerebral Vasospasm After Aneurysmal Subarachnoid Hemorrhage.

Front Neurol 2021 12;12:740338. Epub 2022 Jan 12.

Brain Physics Laboratory, Division of Neurosurgery, Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom.

Common consequences following aneurysmal subarachnoid hemorrhage (aSAH) are cerebral vasospasm (CV), impaired cerebral autoregulation (CA), and disturbance in the autonomic nervous system, as indicated by lower baroreflex sensitivity (BRS). The compensatory interaction between BRS and CA has been shown in healthy volunteers and stable pathological conditions such as carotid atherosclerosis. The aim of this study was to investigate whether the inverse correlation between BRS and CA would be lost in patients after aSAH during vasospasm. A secondary objective was to analyze the time-trend of BRS after aSAH. Retrospective analysis of prospectively collected data was performed at the Neuro-Critical Care Unit of Addenbrooke's Hospital (Cambridge, UK) between June 2010 and January 2012. The cerebral blood flow velocity (CBFV) was measured in the middle cerebral artery using transcranial Doppler ultrasonography (TCD). The arterial blood pressure (ABP) was monitored invasively through an arterial line. CA was quantified by the correlation coefficient (Mxa) between slow oscillations in ABP and CBFV. BRS was calculated using the sequential cross-correlation method using the ABP signal. A total of 73 patients with aSAH were included. The age [median (lower-upper quartile)] was 58 (50-67). WFNS scale was 2 (1-4) and the modified Fisher scale was 3 (1-3). In the total group, 31 patients (42%) had a CV and 42 (58%) had no CV. ABP and CBFV were higher in patients with CV during vasospasm compared to patients without CV ( = 0.001 and < 0.001). There was no significant correlation between Mxa and BRS in patients with CV, neither during nor before vasospasm. In patients without CV, a significant, although moderate correlation was found between BRS and Mxa (r = 0.31; = 0.040), with higher BRS being associated with worse CA. Multiple linear regression analysis showed a significant worsening of BRS after aSAH in patients with CV ( = -0.42; < 0.001). Inverse compensatory correlation between BRS and CA was lost in patients who developed CV after aSAH, both before and during vasospasm. The impact of these findings on the prognosis of aSAH should be investigated in larger studies.
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http://dx.doi.org/10.3389/fneur.2021.740338DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8790510PMC
January 2022

Characterising the dynamics of cerebral metabolic dysfunction following traumatic brain injury: A microdialysis study in 619 patients.

PLoS One 2021 16;16(12):e0260291. Epub 2021 Dec 16.

Division of Neurosurgery, Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom.

Traumatic brain injury (TBI) is a major cause of death and disability, particularly amongst young people. Current intensive care management of TBI patients is targeted at maintaining normal brain physiology and preventing secondary injury. Microdialysis is an invasive monitor that permits real-time assessment of derangements in cerebral metabolism and responses to treatment. We examined the prognostic value of microdialysis parameters, and the inter-relationships with other neuromonitoring modalities to identify interventions that improve metabolism. This was an analysis of prospective data in 619 adult TBI patients requiring intensive care treatment and invasive neuromonitoring at a tertiary UK neurosciences unit. Patients had continuous measurement of intracranial pressure (ICP), arterial blood pressure (ABP), brain tissue oxygenation (PbtO2), and cerebral metabolism and were managed according to a standardized therapeutic protocol. Microdialysate was assayed hourly for metabolites including glucose, pyruvate, and lactate. Cerebral perfusion pressure (CPP) and cerebral autoregulation (PRx) were derived from the ICP and ABP. Outcome was assessed with the Glasgow Outcome Score (GOS) at 6 months. Relationships between monitoring variables was examined with generalized additive mixed models (GAMM). Lactate/Pyruvate Ratio (LPR) over the first 3 to 7 days following injury was elevated amongst patients with poor outcome and was an independent predictor of ordinal GOS (p<0.05). Significant non-linear associations were observed between LPR and cerebral glucose, CPP, and PRx (p<0.001 to p<0.05). GAMM models suggested improved cerebral metabolism (i.e. reduced LPR with CPP >70mmHg, PRx <0.1, PbtO2 >18mmHg, and brain glucose >1mM. Deranged cerebral metabolism is an important determinant of patient outcome following TBI. Variations in cerebral perfusion, oxygenation and glucose supply are associated with changes in cerebral LPR and suggest therapeutic interventions to improve cerebral metabolism. Future prospective studies are required to determine the efficacy of these strategies.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0260291PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8675704PMC
January 2022

Author Correction: Comparison of wavelet and correlation indices of cerebral autoregulation in a pediatric swine model of cardiac arrest.

Sci Rep 2021 Nov 12;11(1):22514. Epub 2021 Nov 12.

Division of Pediatric Anesthesiology, Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University, Baltimore, MD, USA.

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http://dx.doi.org/10.1038/s41598-021-01918-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8590060PMC
November 2021

Causal relationship between slow waves of arterial, intracranial pressures and blood velocity in brain.

Comput Biol Med 2021 12 27;139:104970. Epub 2021 Oct 27.

University of Cambridge, Brain Physics Laboratory, Division of Neurosurgery, Box 167, Addenbrooke's Hospital, Cambridge, CB2 0QQ, United Kingdom.

Purpose: Slow vasogenic waves in arterial blood pressure (ABP), intracranial pressure (ICP) and cerebral blood flow velocity (FV) carry information on multiple brain homeostatic control mechanisms. This work presents an approach to evaluate causal relation between oscillatory modes of these signals as an alternative to time or frequency domain Granger analysis.

Methods: Forty-five patients with simultaneous recordings of ICP, ABP and FV during CSF infusion studies were examined retrospectively. Each time series was decomposed into ten intrinsic mode functions (IMFs) via Ensemble Empirical Mode Decomposition (EEMD) and, afterwards, Granger causality (GC) was computed.

Results: Slow waves of ICP, ABP and FV were reconstructed from mode functions IMF of each time series, covering a frequency range between 0.013 and 0.155 Hz. Most significant connections were from FV to ICP, being stronger during elevation of mean ICP during infusion study. No G-causality was found between any of the IMFs during the baseline phase.

Conclusion: Nonlinearity and nonstationarity of the cerebral and systemic signals can be addressed using EEMD decomposition There is a causal influence of slow waves of FV on slow waves on ICP during the plateau phase of the infusion study for a frequency band between 0.095 and 0.155 Hz. This relationship is magnified during mild intracranial hypertension.
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http://dx.doi.org/10.1016/j.compbiomed.2021.104970DOI Listing
December 2021

Modeling Brain-Heart Crosstalk Information in Patients with Traumatic Brain Injury.

Neurocrit Care 2022 06 12;36(3):738-750. Epub 2021 Oct 12.

Computer Laboratory, University of Cambridge, Cambridge, UK.

Background: Traumatic brain injury (TBI) is an extremely heterogeneous and complex pathology that requires the integration of different physiological measurements for the optimal understanding and clinical management of patients. Information derived from intracranial pressure (ICP) monitoring can be coupled with information obtained from heart rate (HR) monitoring to assess the interplay between brain and heart. The goal of our study is to investigate events of simultaneous increases in HR and ICP and their relationship with patient mortality..

Methods: In our previous work, we introduced a novel measure of brain-heart interaction termed brain-heart crosstalks (ct), as well as two additional brain-heart crosstalks indicators [mutual information ([Formula: see text]) and average edge overlap (ω)] obtained through a complex network modeling of the brain-heart system. These measures are based on identification of simultaneous increase of HR and ICP. In this article, we investigated the relationship of these novel indicators with respect to mortality in a multicenter TBI cohort, as part of the Collaborative European Neurotrauma Effectiveness Research in TBI high-resolution work package.

Results: A total of 226 patients with TBI were included in this cohort. The data set included monitored parameters (ICP and HR), as well as laboratory, demographics, and clinical information. The number of detected brain-heart crosstalks varied (mean 58, standard deviation 57). The Kruskal-Wallis test comparing brain-heart crosstalks measures of survivors and nonsurvivors showed statistically significant differences between the two distributions (p values: 0.02 for [Formula: see text], 0.005 for ct and 0.006 for ω). An inverse correlation was found, computed using the point biserial correlation technique, between the three new measures and mortality: - 0.13 for ct (p value 0.04), - 0.19 for ω (p value 0.002969) and - 0.09 for [Formula: see text] (p value 0.1396). The measures were then introduced into the logistic regression framework, along with a set of input predictors made of clinical, demographic, computed tomography (CT), and lab variables. The prediction models were obtained by dividing the original cohort into four age groups (16-29, 30-49, 50-65, and 65-85 years of age) to properly treat with the age confounding factor. The best performing models were for age groups 16-29, 50-65, and 65-85, with the deviance of ratio explaining more than 80% in all the three cases. The presence of an inverse relationship between brain-heart crosstalks and mortality was also confirmed.

Conclusions: The presence of a negative relationship between mortality and brain-heart crosstalks indicators suggests that a healthy brain-cardiovascular interaction plays a role in TBI.
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http://dx.doi.org/10.1007/s12028-021-01353-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9110542PMC
June 2022

Targeting Autoregulation-Guided Cerebral Perfusion Pressure after Traumatic Brain Injury (COGiTATE): A Feasibility Randomized Controlled Clinical Trial.

J Neurotrauma 2021 10 16;38(20):2790-2800. Epub 2021 Aug 16.

Department of Intensive Care Medicine, University Maastricht (KEMTA), Maastricht University Medical Center+, Maastricht, The Netherlands.

Managing traumatic brain injury (TBI) patients with a cerebral perfusion pressure (CPP) near to the cerebral autoregulation (CA)-guided "optimal" CPP (CPPopt) value is associated with improved outcome and might be useful to individualize care, but has never been prospectively evaluated. This study evaluated the feasibility and safety of CA-guided CPP management in TBI patients requiring intracranial pressure monitoring and therapy (TBIicp patients). The CPPopt Guided Therapy: Assessment of Target Effectiveness (COGiTATE) parallel two-arm feasibility trial took place in four tertiary centers. TBIicp patients were randomized to either the Brain Trauma Foundation (BTF) guideline CPP target range (control group) or to the individualized CA-guided CPP targets (intervention group). CPP targets were guided by six times daily software-based alerts for up to 5 days. The primary feasibility end-point was the percentage of time with CPP concordant (±5 mm Hg) with the set CPP targets. The main secondary safety end-point was an increase in therapeutic intensity level (TIL) between the control and intervention group. Twenty-eight patients were randomized to the control and 32 patients to the intervention group. CPP in the intervention group was in the target range for 46.5% (interquartile range, 41.2-58) of the monitored time, significantly higher than the feasibility target specified in the published protocol (36%;  < 0.001). There were no significant differences between groups for TIL or for other safety end-points. Conclusively, targeting an individual and dynamic CA-guided CPP is feasible and safe in TBIicp patients. This encourages a prospective trial powered for clinical outcomes.
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http://dx.doi.org/10.1089/neu.2021.0197DOI Listing
October 2021

Brain Temperature Influences Intracranial Pressure and Cerebral Perfusion Pressure After Traumatic Brain Injury: A CENTER-TBI Study.

Neurocrit Care 2021 12 30;35(3):651-661. Epub 2021 Jul 30.

Neurological Intensive Care Unit, Fondazione IRCCS (Istituto di Ricovero e Cura a Carattere Scientifico) Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.

Background: After traumatic brain injury (TBI), fever is frequent. Brain temperature (BT), which is directly linked to body temperature, may influence brain physiology. Increased body and/or BT may cause secondary brain damage, with deleterious effects on intracranial pressure (ICP), cerebral perfusion pressure (CPP), and outcome.

Methods: Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI), a prospective multicenter longitudinal study on TBI in Europe and Israel, includes a high resolution cohort of patients with data sampled at a high frequency (from 100 to 500 Hz). In this study, simultaneous BT, ICP, and CPP recordings were investigated. A mixed-effects linear model was used to examine the association between different BT levels and ICP. We additionally focused on changes in ICP and CPP during the episodes of BT changes (Δ BT ≥ 0.5 °C lasting from 15 min to 3 h) up or downward. The significance of ICP and CPP variations was estimated with the paired samples Wilcoxon test (also known as Wilcoxon signed-rank test).

Results: Twenty-one patients with 2,435 h of simultaneous BT and ICP monitoring were studied. All patients reached a BT of 38 °C and experienced at least one episode of ICP above 20 mm Hg. The linear mixed-effects model revealed an association between BT above 37.5 °C and higher ICP levels that was not confirmed for lower BT. We identified 149 episodes of BT changes. During BT elevations (n = 79) ICP increased, whereas CPP was reduced; opposite ICP and CPP variations occurred during episodes of BT reduction (n = 70). All these changes were of moderate clinical relevance (increase of ICP of 4.5 and CPP decrease of 7.5 mm Hg for BT rise, and ICP reduction of 1.7 and CPP elevation of 3.7 mm Hg during BT defervescence), even if statistically significant (p < 0.0001). It has to be noted, however, that a number of therapeutic interventions against intracranial hypertension was documented during those episodes.

Conclusions: Patients after TBI usually develop BT > 38 °C soon after the injury. BT may influence brain physiology, as reflected by ICP and CPP. An association between BT exceeding 37.5 °C and a higher ICP was identified but not confirmed for lower BT ranges. The relationship between BT, ICP, and CPP become clearer during rapid temperature changes. During episodes of temperature elevation, BT seems to have a significant impact on ICP and CPP.
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http://dx.doi.org/10.1007/s12028-021-01294-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8692292PMC
December 2021

CSF Dynamics for Shunt Prognostication and Revision in Normal Pressure Hydrocephalus.

J Clin Med 2021 Apr 15;10(8). Epub 2021 Apr 15.

Brain Physics Laboratory, Division of Neurosurgery, Department of Clinical Neurosciences, University of Cambridge, Cambridge CB2 0QQ, UK.

Background: Despite the quantitative information derived from testing of the CSF circulation, there is still no consensus on what the best approach could be in defining criteria for shunting and predicting response to CSF diversion in normal pressure hydrocephalus (NPH).

Objective: We aimed to review the lessons learned from assessment of CSF dynamics in our center and summarize our findings to date. We have focused on reporting the objective perspective of CSF dynamics testing, without further inferences to individual patient management.

Discussion: No single parameter from the CSF infusion study has so far been able to serve as an unquestionable outcome predictor. Resistance to CSF outflow (Rout) is an important biological marker of CSF circulation. It should not, however, be used as a single predictor for improvement after shunting. Testing of CSF dynamics provides information on hydrodynamic properties of the cerebrospinal compartment: the system which is being modified by a shunt. Our experience of nearly 30 years of studying CSF dynamics in patients requiring shunting and/or shunt revision, combined with all the recent progress made in producing evidence on the clinical utility of CSF dynamics, has led to reconsidering the relationship between CSF circulation testing and clinical improvement.

Conclusions: Despite many open questions and limitations, testing of CSF dynamics provides unique perspectives for the clinician. We have found value in understanding shunt function and potentially shunt response through shunt testing in vivo. In the absence of infusion tests, further methods that provide a clear description of the pre and post-shunting CSF circulation, and potentially cerebral blood flow, should be developed and adapted to the bed-space.
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http://dx.doi.org/10.3390/jcm10081711DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8071572PMC
April 2021

Compliance of the cerebrospinal space: comparison of three methods.

Acta Neurochir (Wien) 2021 07 14;163(7):1979-1989. Epub 2021 Apr 14.

Brain Physics Laboratory, Division of Neurosurgery, Department of Clinical Neurosciences, Addenbrooke's Hospital, University of Cambridge, Cambridge, UK.

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), (b) based on the evaluation of changes in cerebral arterial blood volume (C), and (c) based on the amplitudes of peaks P1 and P2 of ICP pulse waveform (C).

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 vs. C, 0.77 [0.63-0.91] for C vs. C, and 0.68 [0.48-0.91] for C vs. C).

Conclusions: Indirect methods, C and C, 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.
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http://dx.doi.org/10.1007/s00701-021-04834-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8195969PMC
July 2021

Lower Limit of Reactivity Assessed with PRx in an Experimental Setting.

Acta Neurochir Suppl 2021 ;131:275-278

Brain Physics Laboratory, Division of Neurosurgery, Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.

In traumatic brain injury, longer time spent with a cerebral perfusion pressure (CPP) below the pressure reactivity index (PRx)-derived lower limit of reactivity (LLR) has been shown to be statistically associated with higher mortality. We set out to scrutinise the behaviour of LLR and the methods of its estimation in individual cases by performing retrospective analysis of intracranial pressure (ICP), arterial blood pressure (ABP) and laser Doppler flow (LDF) signals recorded in nine piglets undergoing controlled, terminal hypotension. We focused on the sections of the recordings with stable experimental conditions where a clear breakpoint of LDF/CPP characteristic (LLA) could be identified.In eight of the nine experiments, when CPP underwent a monotonous decrease, the relationship PRx/CPP showed two breakpoints (1 - when PRx starts to rise; 2 - when PRx saturates at PRx > 0.3), with LDF-based LLA sitting between them. LLR (CPP at PRx reaching 0.3 in the error bar chart) was close to the lower LLR breakpoint.In conclusion, when CPP has a monotonous decrease, PRx starts worsening before CPP crosses the LLA. A further decrease in CPP below LLA would cause a decrease in CBF, even if the pressure reactivity is not completely lost. This pattern should be taken into account when PRx is used to detect LLA continuously.
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http://dx.doi.org/10.1007/978-3-030-59436-7_51DOI Listing
June 2021

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

Acta Neurochir Suppl 2021 ;131:255-260

Division of Neurosurgery, Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.

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.
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http://dx.doi.org/10.1007/978-3-030-59436-7_48DOI Listing
June 2021

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

Acta Neurochir Suppl 2021 ;131:235-241

Division of Anaesthesia, Department of Medicine, University of Cambridge, Cambridge, UK.

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.
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http://dx.doi.org/10.1007/978-3-030-59436-7_45DOI Listing
June 2021

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

Acta Neurochir Suppl 2021 ;131:231-234

Brain Physics Lab, Division of Neurosurgery, Department of Clinical Neurosciences, Addenbrooke's Hospital, University of Cambridge, Cambridge, UK.

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.
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http://dx.doi.org/10.1007/978-3-030-59436-7_44DOI Listing
June 2021

Methodological Consideration on Monitoring Refractory Intracranial Hypertension and Autonomic Nervous System Activity.

Acta Neurochir Suppl 2021 ;131:211-215

Brain Physics Laboratory, Division of Neurosurgery, Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.

Refractory intracranial hypertension (RIH) refers to a dramatic increase in intracranial pressure (ICP) that cannot be controlled by treatment and leads to patient death. Detrimental sequelae of raised ICP in acute brain injury (ABI) are unclear because the underlying physiopathological mechanisms of raised ICP have not been sufficiently investigated. Recent reports have shown that autonomic activity is altered during changes in ICP. The aim of our study was to evaluate the feasibility of assessing autonomic activity during RIH with our adopted methodology. We selected 24 ABI patients for retrospective review who developed RIH. They were monitored based on ICP, arterial blood pressure, and electrocardiogram using ICM+ software. Secondary parameters reflecting autonomic activity were computed in time and frequency domains through the continuous measurement of heart rate variability and baroreflex sensitivity. The results of the analysis will be presented later in a full paper. This preliminary analysis shows the feasibility of the adopted methodology.
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http://dx.doi.org/10.1007/978-3-030-59436-7_41DOI Listing
June 2021

Spectral Cerebral Blood Volume Accounting for Noninvasive Estimation of Changes in Cerebral Perfusion Pressure in Patients with Traumatic Brain Injury.

Acta Neurochir Suppl 2021 ;131:193-199

Brain Physics Laboratory, Division of Neurosurgery, Department of Clinical Neurosciences, Cambridge Biomedical Campus, Addenbrooke's Hospital, University of Cambridge, Cambridge, UK.

We present the application of a new method for non-invasive cerebral perfusion pressure estimation (spectral nCPP or nCPP) accounting for changes in transcranial Doppler-derived pulsatile cerebral blood volume. Primarily, we analysed cases in which CPP was changing (delta [∆],magnitude of changes]): (1) rise during vasopressor-induced augmentation of ABP (N = 16); and (2) spontaneous changes in intracranial pressure (ICP) during plateau waves (N = 14). Secondarily, we assessed nCPP in a larger cohort in which CPP presented a wider range of values. The average correlation in the time domain between CPP and nCPP for patients undergoing an induced rise in arterial blood pressure (ABP) was 0.95 ± 0.07. For the greater traumatic brain injury (TBI) cohort, this correlation was 0.63 ± 0.37. ∆ correlations between mean values of CPP and nCPP were 0.73 (p = 0.002) and 0.78 (p < 0.001) respectively for induced rise in ABP and ICP plateau wave cohorts. The area under the curve (AUC) for ∆CPP was of 0.71 with a 95% confidence interval of 0.54-0.88. To detect low CPP, AUC was 0.817 with a 95% confidence interval of 0.79-0.85. nCPP can reliably identify changes in direct CPP across time and the magnitude of these changes in absolute values. The ability to detect changes in CPP is reasonable but stronger for detecting low CPP, ≤70 mmHg.
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http://dx.doi.org/10.1007/978-3-030-59436-7_38DOI Listing
June 2021

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

Acta Neurochir Suppl 2021 ;131:181-185

Brain Physics Laboratory, Division of Neurosurgery, Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.

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.
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http://dx.doi.org/10.1007/978-3-030-59436-7_36DOI Listing
June 2021

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?

Acta Neurochir Suppl 2021 ;131:173-179

Brain Physics Laboratory, Division of Neurosurgery, Department of Clinical Neurosciences, Addenbrooke's Hospital, University of Cambridge, Cambridge, UK.

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.
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http://dx.doi.org/10.1007/978-3-030-59436-7_35DOI Listing
June 2021

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

Acta Neurochir Suppl 2021 ;131:167-172

Department of Intensive Care, University Maastricht, Maastricht University Medical Center, Maastricht, The Netherlands.

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.
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http://dx.doi.org/10.1007/978-3-030-59436-7_34DOI Listing
June 2021

Usability of Noninvasive Counterparts of Traditional Autoregulation Indices in Traumatic Brain Injury.

Acta Neurochir Suppl 2021 ;131:163-166

Brain Physics Laboratory, Division of Neurosurgery, Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.

The pressure reactivity index (PRx) and the pulse amplitude index (PAx) are invasively determined parameters that are commonly used to describe autoregulation following traumatic brain injury (TBI). Using a transcranial Doppler ultrasound (TCD) technique, it is possible to approximate cerebral arterial blood volume (CaBV) solely from cerebral blood flow velocities, and further, to calculate non-invasive markers of autoregulation. In this brief study, we aimed to investigate whether the estimation of relative CaBV with different models could describe the cerebrovascular reactivity of TBI patients. PRx, PAx and their non-invasive counterparts (nPRx and nPAx) were calculated retrospectively from data collected during the monitoring of TBI patients. CaBV, an essential parameter for the calculation of nPRx and nPAx, was determined with both a continuous flow forward (CFF) model-considering a non-pulsatile blood outflow from the brain-and a pulsatile flow forward (PFF) model, presuming a pulsatile outflow. We found that the estimated CaBV demonstrates good coherence with ICP and that nPRx and nPAx can describe cerebrovascular reactivity similarly to PRx and PAx. Continuous monitoring with TCD is difficult, so the usability of PRx and PAx is limited. However, they might become useful for clinicians in the near future owing to rapid advances in these technologies.
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http://dx.doi.org/10.1007/978-3-030-59436-7_33DOI Listing
June 2021

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.

Acta Neurochir Suppl 2021 ;131:143-147

Department of Intensive Care Medicine, University of Maastricht, Maastricht University Medical Centre, Maastricht, The Netherlands.

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.
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http://dx.doi.org/10.1007/978-3-030-59436-7_29DOI Listing
June 2021

Cerebrovascular Consequences of Elevated Intracranial Pressure After Traumatic Brain Injury.

Acta Neurochir Suppl 2021 ;131:43-48

Division of Neurosurgery, Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.

We compared various descriptors of cerebral hemodynamics in 517 patients with traumatic brain injury (TBI) who had, on average, elevated (>23 mmHg) or normal (<15 mmHg) intracranial pressure (ICP). In a subsample of 193 of those patients, transcranial Doppler ultrasound (TCD) recordings were made. Arterial blood pressure (ABP), cerebral blood flow velocity (CBFV), cerebral autoregulation indices based on TCD (the mean flow index (Mx; the coefficient of correlation between the the cerebral perfusion pressure CPP and flow velocity) and the autoregulation index (ARI)), and the pressure reactivity index (PRx) were compared between groups. We also analyzed the TCD-based cerebral blood flow (CBF) index (diastolic CBFV/mean CBFV), the spectral pulsatility index (sPI), and the critical closing pressure (CrCP). Finally, we also looked at brain tissue oxygenation (cerebral oxygen partial tension (PbtO)) in 109 patients. The mean cerebral perfusion pressure (CPP) was lower in the group with elevated ICP (p < 0.01), despite a higher mean arterial pressure (MAP) (p < 0.005) and worse autoregulation (as assessed with the Mx, ARI, and PRx indices), greater CrCP, a lower CBF index, and a higher sPI (all with p values of <0.001). Neither the mean CBFV nor PbtO reached significant differences between groups. Mortality in the group with elevated ICP was almost three times greater than that in the group with normal ICP (45% versus 17%). Elevated ICP affects cerebral autoregulation. When autoregulation is not working properly, the brain is exposed to ischemic insults whenever CPP falls.
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http://dx.doi.org/10.1007/978-3-030-59436-7_10DOI Listing
June 2021

Analysis of Cardio-Cerebral Crosstalk Events in an Adult Cohort from the CENTER-TBI Study.

Acta Neurochir Suppl 2021 ;131:39-42

Computer Laboratory, University of Cambridge, Cambridge, UK.

Objective: In a previous study, we observed the presence of simultaneous increases in intracranial pressure (ICP) and the heart rate (HR), which we denominated cardio-cerebral crosstalk (CC), and we related the number of such events to patient outcomes in a paediatric cohort. In this chapter, we present an extension of this work to an adult cohort from the Collaborative European NeuroTrauma Effectiveness Research in TBI (CENTER-TBI) study.

Methods: We implemented a sliding window algorithm to detect CC events. We considered subwindows of 10-min observations. If simultaneous increases of at least 20% in ICP and HR occurred with respect to the minimum ICP and HR values in the time windows, a CC event was detected. Correlation between the number of CC events and mortality was then obtained.

Results: The cohort consisted of 226 adults (aged 16-85 years). The number of CC events that were detected varied (mean 50, standard deviation 58). A point biserial correlation coefficient of -0.13 between mortality and CC was found. Although the correlation was weaker than that seen in the paediatric cohort (-0.30), the negative direction was replicated.

Conclusion: In this work, we first extracted CC events from ICP and HR observations of adult patients with traumatic brain injury and related the number of CC events to patient outcomes. Consistency with the previous results in the paediatric cohort was observed. The more crosstalk events occurred, the better the patient outcome was.
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http://dx.doi.org/10.1007/978-3-030-59436-7_9DOI Listing
June 2021

External Hydrocephalus After Traumatic Brain Injury: Retrospective Study of 102 Patients.

Acta Neurochir Suppl 2021 ;131:35-38

Brain Physics Laboratory, Division of Neurosurgery, Department of Clinical Neuroscience, Addenbrooke's Hospital, University of Cambridge, Cambridge, UK.

Introduction: External hydrocephalus (EH) refers to impairment of extra-axial cerebrospinal fluid flow with enlargement of the subarachnoid space (SAS) and concomitant raised intracranial pressure (ICP). It is often confused with a subdural hygroma and overlooked, particularly when there is no ventricular enlargement. In this study, we aimed to describe the epidemiology of EH in a large population of adults with traumatic brain injury (TBI).

Methods: This observational, retrospective cohort study was conducted in adult patients who were admitted with TBI to the Department of Clinical Neuroscience at Addenbrooke's Hospital (Cambridge, UK) over a period of 3 years (2014-2017). Patients were included in the study if they had ICP monitoring and at least three CT scans within the first 21 days to assess SAS evolution. Patients who underwent a decompressive craniectomy were excluded. SAS was assessed individually on each CT scan by two independent investigators. ICP data were analysed with ICM+ software (Cambridge Enterprise Ltd., Cambridge, UK). Short-term and 6-month outcomes were examined. The groups of patients with and without EH were compared.

Results: Of the 102 patients included in the study, 30.4% developed EH after a delay of 2.98 ± 2.4 days. The initial Glasgow Coma Scale (GCS) scores did not differ between patients with and without EH. Subarachnoid haemorrhage was found to be the main risk factor for EH. Patients with EH required a significantly longer period of mechanical ventilation (+6.9 days), were more likely to have a tracheostomy (55% versus 33%), and had a longer stay in the intensive care unit (+8.5 days). ICP was higher during the 48 h after diagnosis of EH than during the previous 48 h. EH survivors had a lower mean Glasgow Outcome Scale Extended (GOS-E) score (4.6 versus 5.9, P = 0.031) and were more likely to receive a permanent shunt for secondary hydrocephalus (17.4% versus 1.8%, odds ratio 7.1).

Conclusion: In adults with TBI, EH remains insufficiently understood and probably underdiagnosed. This study showed that it is a frequent complication of TBI, with significant clinical consequences.
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http://dx.doi.org/10.1007/978-3-030-59436-7_8DOI Listing
June 2021

Comparison of Two Intracranial Pressure Calculation Methods and Their Effects on the Mean Intracranial Pressure and Intracranial Pressure Dose.

Acta Neurochir Suppl 2021 ;131:31-33

Brain Physics Laboratory, Division of Neurosurgery, Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.

This study compared two methods of calculating the intracranial pressure (ICP) in a patient: end-hour ICP and hour-averaged ICP. A total of 1060 patients with traumatic brain injury and a known clinical outcome were studied. For each patient, the end-hour ICP and hour-averaged ICP were calculated. The mean ICP and the ICP dose above 20 mmHg were evaluated using both calculation methods. The results for patients who survived and those who died were compared using a Student's t test. The average correlation between the end-hour and hour-averaged mean ICP was 0.747, indicating that the end-hour ICP method agrees moderately with the hour-averaged method. However, the comparison between surviving and dead patients did not present significant differences between ICP values averaged with these two different methods. The Student's t test gave similar results for both the mean ICP and ICP dose. The results suggest that the end-hour and hour-averaged methods have similar predictive power for patients' clinical outcome.
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http://dx.doi.org/10.1007/978-3-030-59436-7_7DOI Listing
June 2021

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

Acta Neurochir Suppl 2021 ;131:23-25

Brain Physics Laboratory, Division of Neurosurgery, Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.

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.
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http://dx.doi.org/10.1007/978-3-030-59436-7_5DOI Listing
June 2021

Visualization of Intracranial Pressure Insults After Severe Traumatic Brain Injury: Influence of Individualized Limits of Reactivity.

Acta Neurochir Suppl 2021 ;131:7-10

Academic Neurosurgery, University of Cambridge, Cambridge, UK.

Cerebral perfusion pressure (CPP) lower limits of reactivity can be determined almost continuously after severe traumatic brain injury (TBI), and deviation below the lower limit carries important prognostic information. In this study, we used a recently derived coloured contour method for visualizing intracranial pressure (ICP) insults to describe the influence of having a CPP above the CPP lower limits of reactivity after severe TBI. In a cohort of 729 patients, we examined the relationship between ICP insults and the 6-month Glasgow Outcome Scale score, using colour-coded plots, as described previously. We then assessed this relationship when ICP insults were above or below the CPP lower limit of reactivity. We found a curvilinear relationship whereby even prolonged durations of low-intensity ICP insults were not associated with poor outcomes but short durations of high-intensity insults were. When only ICP insults with a CPP below the CPP lower limit of reactivity were considered, a much lower intensity of ICP insults could be tolerated. A CPP above the lower limits of reactivity exerts a protective effect, whereas a CPP below the lower reactivity limits renders the patient vulnerable to increased morbidity from intracranial hypertension.
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http://dx.doi.org/10.1007/978-3-030-59436-7_2DOI Listing
June 2021

Association of transcranial Doppler blood flow velocity slow waves with delayed cerebral ischemia in patients suffering from subarachnoid hemorrhage: a retrospective study.

Intensive Care Med Exp 2021 Mar 26;9(1):11. Epub 2021 Mar 26.

Academic Neurosurgery Unit, Brain Physics Lab, Addenbrooke's Hospital, Box 167, Cambridge, CB20QQ, UK.

Background: Cerebral vasospasm (VS) and delayed cerebral ischemia (DCI) constitute major complications following subarachnoid hemorrhage (SAH). A few studies have examined the relationship between different indices of cerebrovascular dynamics with the occurrence of VS. However, their potential association with the development of DCI remains elusive. In this study, we investigated the pattern of changes of different transcranial Doppler (TCD)-derived indices of cerebrovascular dynamics during vasospasm in patients suffering from subarachnoid hemorrhage, dichotomized by the presence of delayed cerebral ischemia.

Methods: A retrospective analysis was performed using recordings from 32 SAH patients, diagnosed with VS. Patients were divided in two groups, depending on development of DCI. Magnitude of slow waves (SWs) of cerebral blood flow velocity (CBFV) was measured. Cerebral autoregulation was estimated using the moving correlation coefficient Mxa. Cerebral arterial time constant (tau) was expressed as the product of resistance and compliance. Complexity of CBFV was estimated through measurement of sample entropy (SampEn).

Results: In the whole population (N = 32), magnitude of SWs of ipsilateral to VS side CBFV was higher during vasospasm (4.15 ± 1.55 vs before: 2.86 ± 1.21 cm/s, p < 0.001). Ipsilateral SWs of CBFV before VS had higher magnitude in DCI group (N = 19, p < 0.001) and were strongly predictive of DCI, with area under the curve (AUC) = 0.745 (p = 0.02). Vasospasm caused a non-significant shortening of ipsilateral values of tau and increase in SampEn in all patients related to pre-VS measurements, as well as an insignificant increase of Mxa in DCI related to non-DCI group (N = 13).

Conclusions: In patients suffering from subarachnoid hemorrhage, TCD-detected VS was associated with higher ipsilateral CBFV SWs, related to pre-VS measurements. Higher CBFV SWs before VS were significantly predictive of delayed cerebral ischemia.
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http://dx.doi.org/10.1186/s40635-021-00378-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7994457PMC
March 2021

Cerebral autoregulation in the operating room and intensive care unit after cardiac surgery.

Br J Anaesth 2021 May 23;126(5):967-974. Epub 2021 Mar 23.

Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA. Electronic address:

Background: Cerebral autoregulation monitoring is a proposed method to monitor perfusion during cardiac surgery. However, limited data exist from the ICU as prior studies have focused on intraoperative measurements. Our objective was to characterise cerebral autoregulation during surgery and early ICU care, and as a secondary analysis to explore associations with delirium.

Methods: In patients undergoing cardiac surgery (n=134), cerebral oximetry values and arterial BP were monitored and recorded until the morning after surgery. A moving Pearson's correlation coefficient between mean arterial proessure (MAP) and near-infrared spectroscopy signals generated the cerebral oximetry index (COx). Three metrics were derived: (1) globally impaired autoregulation, (2) MAP time and duration outside limits of autoregulation (MAP dose), and (3) average COx. Delirium was assessed using the 3-Minute Diagnostic Interview for CAM-defined Delirium (3D-CAM) and the Confusion Assessment Method for the ICU (CAM-ICU). Autoregulation metrics were compared using χ and rank-sum tests, and associations with delirium were estimated using regression models, adjusted for age, bypass time, and logEuroSCORE.

Results: The prevalence of globally impaired autoregulation was higher in the operating room vs ICU (40% vs 13%, P<0.001). The MAP dose outside limits of autoregulation was similar in the operating room and ICU (median 16.9 mm Hg×h; inter-quartile range [IQR] 10.1-38.8 vs 16.9 mm Hg×h; IQR 5.4-35.1, P=0.20). In exploratory adjusted analyses, globally impaired autoregulation in the ICU, but not the operating room, was associated with delirium. The MAP dose outside limits of autoregulation in the operating room and ICU was also associated with delirium.

Conclusions: Metrics of cerebral autoregulation are altered in the ICU, and may be clinically relevant with respect to delirium. Further studies are needed to investigate these findings and determine possible benefits of autoregulation-based MAP targeting in the ICU.
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http://dx.doi.org/10.1016/j.bja.2020.12.043DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8132879PMC
May 2021
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