Publications by authors named "Peter Smielewski"

276 Publications

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 Apr 14. 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
April 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
January 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
January 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
January 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
January 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
January 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
January 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
January 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
January 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
January 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
January 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
January 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
January 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
January 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
January 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
January 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
January 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
January 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
May 2021

Impact of Arterial Carbon Dioxide and Oxygen Content on Cerebral Autoregulation Monitoring Among Children Supported by ECMO.

Neurocrit Care 2021 Mar 9. Epub 2021 Mar 9.

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

Background: Cerebral autoregulation (CA) impairment is associated with neurological complications among children supported by extracorporeal membrane oxygenation (ECMO). Severe variations of arterial CO (PaCO) and O (PaO) tension after ECMO onset are common and associate with mortality and poor neurological outcome. The impact of gas exchange on CA among critically ill patients is poorly studied.

Methods: Retrospective analysis of data collected prospectively from 30 children treated with veno-arterial or veno-venous ECMO in the PICU of Nantes University Hospital, France. A correlation coefficient between the variations of regional cerebral oxygen saturation (rSO) and the variations of mean arterial blood pressure (MAP) was calculated as an index of CA (cerebral oxygenation reactivity index, COx). Cox-MAP plots were investigated allowing determining lower limit of autoregulation (LLA) and upper limit of autoregulation (ULA) limits of autoregulation. Age-based normal blood pressure was used to adjust the MAP, LLA, and ULA data from each patient and then reported as percentage (nMAP, nLLA, and nULA, respectively). RSO, COx, nMAP, nLLA, and nULA values were averaged over one hour before each arterial blood gas (ABG) sample during ECMO run.

Results: Thirty children (median age 4.8 months [Interquartile range (IQR) 0.7-39.1], median weight 5 kg [IQR 4-15]) experiencing 31 ECMO runs were included in the study. Three hundred and ninety ABGs were analyzed. The highest values of COx were observed on day 1 (D1) of ECMO. The relationship between COx and PaCO was nonlinear, but COx values tended to be lower in case of hypercapnia compared to normocapnia. During the whole ECMO run, a weak but significant correlation between PaCO and nULA was observed (R = 0.432, p = 0.02). On D1 of ECMO, this correlation was stronger (R = 0.85, p = 0.03) and a positive correlation between nLLA and PaCO was also found (R = 0.726, p < 0.001). A very weak negative correlation between PaO and nULA was observed within the whole ECMO run and on D1 of ECMO (R =  -0.07 p = 0.04 and R =  -0.135 p =  <0.001, respectively). The difference between nULA and nLLA representing the span of the autoregulation plateau was positively correlated with PaCO and negatively correlated with PaO (R = 0.224, p = 0.01 and R =  -0.051, p = 0.004, respectively).

Conclusions: We observed a complex relationship between PaCO and CA, influenced by the level of blood pressure. Hypercapnia seems to be globally protective in normotensive or hypertensive condition, while, in case of very low MAP, hypercapnia may disturb CA as it increases LLA. These data add additional arguments for very cautiously lower PaCO, especially after ECMO start.
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http://dx.doi.org/10.1007/s12028-021-01201-8DOI Listing
March 2021

Delay of cerebral autoregulation in traumatic brain injury patients.

Clin Neurol Neurosurg 2021 Mar 8;202:106478. Epub 2021 Jan 8.

Brain Physics Laboratory, Department of Clinical Neurosciences, Addenbrooke's Hospital, University of Cambridge, Hills Rd, Cambridge CB2 0QQ, United Kingdom. Electronic address:

Introduction: Adequate cerebral perfusion prevents secondary insult after traumatic brain injury (TBI). Cerebral autoregulation (CAR) keeps cerebral blood flow (CBF) constant when arterial blood pressure (ABP) changes. Aim of the study was to evaluate the existence of delayed CAR in TBI patients and its possible association with outcome.

Methods: We retrospectively analysed TBI patients. Flow velocity (FV) in middle cerebral artery, invasive intra-cranial pressure (ICP) and ABP were recorded. Cerebral perfusion pressure (CPP) was calculated as ABP - ICP. Mean flow index (Mx) > 0.3 defined altered CAR. Samples from patients with altered CAR were further analysed: FV signal was shifted backward relative to CPP; Mx was calculated after each shift (MxD). Mx > 0.3 plus MxD ≤ 0.3 defined delayed CAR. Favourable outcome (FO) at 6 months was defined as Glasgow Outcome Scale 4-5.

Results: 154 patients were included. GCS was 6 [4-9], ICP was 14 [9-20] mmHg. Data on 6 months outcome were available for 131 patients: 104/131 patients (79 %) were alive; GOS was 4 [3-5]; 70/131 (53 %) had FO. Mx was 0.07 [-0.19 to 0.28] overall. Mx was lower in patients with FO compared others (0.00 [-0.21 to 0.20] vs 0.17 [-0.12 to 0.37], p = 0.02). 118 (77 %) patients had intact CAR and 36 (23 %) patients had altered CAR; 23 patients - 15 % of the general cohort and 64 % of patients with altered CAR - had delayed CAR. Delay in the autoregulatory response was 2 [1-4] seconds. 80/98 (82 %) of patients with intact CAR survived, compared to 16/21 (76 %) with delayed and 8/12 (67 %) with altered CAR (p = 0.20). 80/98 (58 %) patients with intact, 10/21 (48 %) patients with delayed and 3/12 (25 %) patients with altered CAR had FO (p = 0.03).

Conclusion: A subgroup of TBI patients with delayed CAR was identified. Delayed CAR was associated with better neurological outcome than altered CAR.
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http://dx.doi.org/10.1016/j.clineuro.2021.106478DOI Listing
March 2021

Transcranial Doppler-derived indices of cerebrovascular haemodynamics are independent of depth and angle of insonation.

J Clin Neurosci 2020 Dec 6;82(Pt A):115-121. Epub 2020 Nov 6.

University of New South Wales, South Western Sydney Clinical School, Liverpool, NSW, Australia; Illawarra Health and Medical Research Institute, Wollongong, NSW, Australia; Department of Neurosurgery, Wollongong Hospital, Wollongong, NSW, Australia.

Continuous measurement of cerebral blood flow velocity (CBFV) of the middle cerebral artery (MCA) using transcranial Doppler (TCD) and arterial blood pressure (ABP) monitoring enables assessment of cerebrovascular haemodynamics. Further indices describing cerebrovascular function can be calculated from ABP and CBFV, such as the mean index (Mxa) of cerebrovascular autoregulation, the 'time constant of the cerebral arterial bed' (tau), the 'critical closing pressure' (CrCP) and a 'non-invasive estimator of ICP' (nICP). However, TCD is operator-dependent and changes in angle and depth of MCA insonation result in different readings of CBFV. The effect of differing CBFV readings on the calculated secondary indices remains unknown. The aim of this study was to investigate variation in angle and depth of MCA insonation on these secondary indices. In eight patients continuous ABP and ipsilateral CBFV monitoring was performed using two different TCD probes, resulting in four simultaneous CBFV readings at different angles and depths per patient. From all individual recordings, the K-means clustering algorithm was applied to the four simultaneous longitudinal measurements. The average ratios of the between-clusters, sum-of-squares and total sum-of-squares were significantly higher for CBFV than for the indices Mxa, tau and CrCP (p < 0.001, p = 0.007 and p = 0.016) but not for nICP (p = 0.175). The results indicate that Mxa, tau and CrCP seemed to be not affected by depth and angle of TCD insonation, whereas nICP was.
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http://dx.doi.org/10.1016/j.jocn.2020.10.037DOI Listing
December 2020

Impact of duration and magnitude of raised intracranial pressure on outcome after severe traumatic brain injury: A CENTER-TBI high-resolution group study.

PLoS One 2020 14;15(12):e0243427. Epub 2020 Dec 14.

Department of Physiology and Pharmacology, Section of Perioperative Medicine and Intensive Care, Karolinska Institutet, Stockholm, Sweden.

Magnitude of intracranial pressure (ICP) elevations and their duration have been associated with worse outcomes in patients with traumatic brain injuries (TBI), however published thresholds for injury vary and uncertainty about these levels has received relatively little attention. In this study, we have analyzed high-resolution ICP monitoring data in 227 adult patients in the CENTER-TBI dataset. Our aim was to identify thresholds of ICP intensity and duration associated with worse outcome, and to evaluate the uncertainty in any such thresholds. We present ICP intensity and duration plots to visualize the relationship between ICP events and outcome. We also introduced a novel bootstrap technique to evaluate uncertainty of the equipoise line. We found that an intensity threshold of 18 ± 4 mmHg (2 standard deviations) was associated with worse outcomes in this cohort. In contrast, the uncertainty in what duration is associated with harm was larger, and safe durations were found to be population dependent. The pressure and time dose (PTD) was also calculated as area under the curve above thresholds of ICP. A relationship between PTD and mortality could be established, as well as for unfavourable outcome. This relationship remained valid for mortality but not unfavourable outcome after adjusting for IMPACT core variables and maximum therapy intensity level. Importantly, during periods of impaired autoregulation (defined as pressure reactivity index (PRx)>0.3) ICP events were associated with worse outcomes for nearly all durations and ICP levels in this cohort and there was a stronger relationship between outcome and PTD. Whilst caution should be exercised in ascribing causation in observational analyses, these results suggest intracranial hypertension is poorly tolerated in the presence of impaired autoregulation. ICP level guidelines may need to be revised in the future taking into account cerebrovascular autoregulation status considered jointly with ICP levels.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0243427PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7735618PMC
January 2021

Autonomic Nervous System Activity during Refractory Rise in Intracranial Pressure.

J Neurotrauma 2021 Jan 12. Epub 2021 Jan 12.

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

Refractory intracranial hypertension (RIH) is a dramatic increase in intracranial pressure (ICP) that cannot be controlled by treatment. Recent reports suggest that the autonomic nervous system (ANS) activity may be altered during changes in ICP. Our study aimed to assess ANS activity during RIH and the causal relationship between rising in ICP and autonomic activity. We reviewed retrospectively 24 multicenter (Cambridge, Tromso, Berlin) patients in whom RIH developed as a pre-terminal event after acute brain injury (ABI). They were monitored with ICP, arterial blood pressure (ABP), and electrocardiography (ECG) using ICM+ software. Parameters reflecting autonomic activity were computed in time and frequency domain through the measurement of heart rate variability (HRV) and baroreflex sensitivity (BRS). Our results demonstrated that a rise in ICP was associated to a significant rise in HRV and BRS with a higher significance level in the high-frequency HRV ( < 0.001). This increase was followed by a significant decrease in HRV and BRS above the upper-breakpoint of ICP where ICP pulse-amplitude starts to decrease whereas the mean ICP continues to rise. Temporality measured with a Granger test suggests a causal relationship from ICP to ANS. The above results suggest that a rise in ICP interacts with ANS activity, mainly interfacing with the parasympathetic-system. The ANS seems to react to the rise in ICP with a response possibly focused on maintaining the cerebrovascular homeostasis. This happens until the critical threshold of ICP is reached above which the ANS variables collapse, probably because of low perfusion of the brain and the central autonomic network.
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http://dx.doi.org/10.1089/neu.2020.7091DOI Listing
January 2021

Determining Thresholds for Three Indices of Autoregulation to Identify the Lower Limit of Autoregulation During Cardiac Surgery.

Crit Care Med 2021 Apr;49(4):650-660

Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD.

Objectives: Monitoring cerebral autoregulation may help identify the lower limit of autoregulation in individual patients. Mean arterial blood pressure below lower limit of autoregulation appears to be a risk factor for postoperative acute kidney injury. Cerebral autoregulation can be monitored in real time using correlation approaches. However, the precise thresholds for different cerebral autoregulation indexes that identify the lower limit of autoregulation are unknown. We identified thresholds for intact autoregulation in patients during cardiopulmonary bypass surgery and examined the relevance of these thresholds to postoperative acute kidney injury.

Design: A single-center retrospective analysis.

Setting: Tertiary academic medical center.

Patients: Data from 59 patients was used to determine precise cerebral autoregulation thresholds for identification of the lower limit of autoregulation. These thresholds were validated in a larger cohort of 226 patients.

Methods And Main Results: Invasive mean arterial blood pressure, cerebral blood flow velocities, regional cortical oxygen saturation, and total hemoglobin were recorded simultaneously. Three cerebral autoregulation indices were calculated, including mean flow index, cerebral oximetry index, and hemoglobin volume index. Cerebral autoregulation curves for the three indices were plotted, and thresholds for each index were used to generate threshold- and index-specific lower limit of autoregulations. A reference lower limit of autoregulation could be identified in 59 patients by plotting cerebral blood flow velocity against mean arterial blood pressure to generate gold-standard Lassen curves. The lower limit of autoregulations defined at each threshold were compared with the gold-standard lower limit of autoregulation determined from Lassen curves. The results identified the following thresholds: mean flow index (0.45), cerebral oximetry index (0.35), and hemoglobin volume index (0.3). We then calculated the product of magnitude and duration of mean arterial blood pressure less than lower limit of autoregulation in a larger cohort of 226 patients. When using the lower limit of autoregulations identified by the optimal thresholds above, mean arterial blood pressure less than lower limit of autoregulation was greater in patients with acute kidney injury than in those without acute kidney injury.

Conclusions: This study identified thresholds of intact and impaired cerebral autoregulation for three indices and showed that mean arterial blood pressure below lower limit of autoregulation is a risk factor for acute kidney injury after cardiac surgery.
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http://dx.doi.org/10.1097/CCM.0000000000004737DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7979429PMC
April 2021

Robotic Semi-Automated Transcranial Doppler Assessment of Cerebrovascular Autoregulation in Post-Concussion Syndrome: Methodological Considerations.

Neurotrauma Rep 2020 25;1(1):218-231. Epub 2020 Nov 25.

Division of Neurosurgery, University of Cambridge and Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom.

Post-concussion syndrome (PCS) refers to a constellation of physical, cognitive, and emotional symptoms after traumatic brain injury (TBI). Despite its incidence and impact, the underlying mechanisms of PCS are unclear. We hypothesized that impaired cerebral autoregulation (CA) is a contributor. In this article, we present our protocol for non-invasively assessing CA in patients with TBI and PCS in a real-world clinical setting. A prospective, observational study was integrated into outpatient clinics at a tertiary neurosurgical center. Data points included: demographics, symptom profile (Post-Concussion Symptom Scale [PCSS]) and neuropsychological assessment (Cambridge Neuropsychological Test Automated-Battery [CANTAB]). Cerebrovascular metrics (nMxa co-efficient and the transient hyperaemic-response ratio [THRR]) were collected using transcranial Doppler (TCD), finger plethysmography, and bespoke software (ICM+). Twelve participants were initially recruited but 2 were excluded after unsuccessful insonation of the middle cerebral artery (MCA); 10 participants (5 patients with TBI, 5 healthy controls) were included in the analysis (median age 26.5 years, male to female ratio: 7:3). Median PCSS scores were 6/126 for the TBI patient sub-groups. Median CANTAB percentiles were 78 (healthy controls) and 25 (TBI). nMxa was calculated for 90% of included patients, whereas THRR was calculated for 50%. Median study time was 127.5 min and feedback ( = 6) highlighted the perceived acceptability of the study. This pilot study has demonstrated a reproducible assessment of PCS and CA metrics (non-invasively) in a real-world setting. This protocol is feasible and is acceptable to participants. By scaling this methodology, we hope to test whether CA changes are correlated with symptomatic PCS in patients post-TBI.
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http://dx.doi.org/10.1089/neur.2020.0021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7703686PMC
November 2020

The Effect of Temperature Increases on Brain Tissue Oxygen Tension in Patients with Traumatic Brain Injury: A Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury Substudy.

Ther Hypothermia Temp Manag 2020 Nov 17. Epub 2020 Nov 17.

Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria.

Fever may aggravate secondary brain injury after traumatic brain injury (TBI). The aim of this study was to identify episodes of temperature increases through visual plot analysis and algorithm supported detection, and to describe associated patterns of changes in on brain tissue oxygen tension (PO). Data derive from the high-resolution cohort of the multicenter prospective Collaborative European NeuroTrauma Effectiveness Research in TBI (CENTER-TBI) study. Temperature increases (≥0.5°C) were visually identified in 33 patients within the first 11 days of monitoring. Generalized estimating equations were used to detect significant changes of systemic and neuromonitoring parameters from baseline to the highest temperature. Patients were median 50 (interquartile range [IQR], 35-62) years old, and presented with a Glasgow Coma Scale (GCS) of 8 (IQR, 4-10). In 202 episodes of temperature increases, mean temperature rose by 1.0°C ± 0.5°C within 4 hours. Overall, PO slightly increased (ΔPO = 0.9 ± 6.1 mmHg,  = 0.022) during temperature increases. PO increased in 35% ( < 0.001), was stable in 49% ( = 0.852), and decreased in 16% ( < 0.001) of episodes. During episodes of temperature increases and simultaneous drops in PO, cerebral perfusion pressure (CPP) decreased (ΔCPP -6.3 ± 11.5 mmHg;  < 0.001). Brain tissue hypoxia (PO <20 mmHg) developed during 27/164 (17%) episodes of effervescences, in the remaining 38/202 episodes baseline PO was already <20 mmHg. Comparable results were found when using algorithm-supported detection of temperature increases. In conclusion, during effervescences, PO was mostly stable or slightly increased. A decrease of PO was observed in every sixth episode, where it was associated with a decrease in CPP. Our data highlight the need for special attention to CPP monitoring and maintenance during episodes of fever.
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http://dx.doi.org/10.1089/ther.2020.0027DOI Listing
November 2020