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Poor postoperative outcomes may be associated with cerebral ischaemia or hyperaemia, caused by episodes of arterial blood pressure (ABP) being outside the range of cerebral autoregulation (CA). Monitoring CA using COx (correlation between slow changes in mean ABP and regional cerebral O2 saturation-rSO2) could allow to individualise the management of ABP to preserve CA. We aimed to explore a continuous automated assessment of ABPOPT (ABP where CA is best preserved) and ABP at the lower limit of autoregulation (LLA) in elective neurosurgery patients. Retrospective analysis of prospectively collected data of 85 patients [median age 60 (IQR 51-68)] undergoing elective neurosurgery. ABPBASELINE was the mean of 3 pre-operative non-invasive measurements. ABP and rSO2 waveforms were processed to estimate COx-derived ABPOPT and LLA trend-lines. We assessed: availability (number of patients where ABPOPT/LLA were available); time required to achieve first values; differences between ABPOPT/LLA and ABP. ABPOPT and LLA availability was 86 and 89%. Median (IQR) time to achieve the first value was 97 (80-155) and 93 (78-122) min for ABPOPT and LLA respectively. Median ABPOPT [75 (69-84)] was lower than ABPBASELINE [90 (84-95)] (p < 0.001, Mann-U test). Patients spent 72 (56-86) % of recorded time with ABP above or below ABPOPT ± 5 mmHg. ABPOPT and ABP time trends and variability were not related to each other within patients. 37.6% of patients had at least 1 hypotensive insult (ABP < LLA) during the monitoring time. It seems possible to assess individualised automated ABP targets during elective neurosurgery.
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Presión Arterial , Presión Sanguínea , Circulación Cerebrovascular , Procedimientos Quirúrgicos Electivos , Homeostasis , Procedimientos Neuroquirúrgicos , Humanos , Femenino , Persona de Mediana Edad , Masculino , Anciano , Estudios Retrospectivos , Procedimientos Neuroquirúrgicos/métodos , Determinación de la Presión Sanguínea/métodos , Saturación de Oxígeno , Monitoreo Intraoperatorio/métodos , Isquemia Encefálica/fisiopatología , Encéfalo , Monitoreo Fisiológico/métodosRESUMEN
BACKGROUND: A previous retrospective single-centre study suggested that the percentage of time spent with cerebral perfusion pressure (CPP) below the individual lower limit of reactivity (LLR) is associated with mortality in traumatic brain injury (TBI) patients. We aim to validate this in a large multicentre cohort. METHODS: Recordings from 171 TBI patients from the high-resolution cohort of the CENTER-TBI study were processed with ICM+ software. We derived LLR as a time trend of CPP at a level for which the pressure reactivity index (PRx) indicates impaired cerebrovascular reactivity with low CPP. The relationship with mortality was assessed with Mann-U test (first 7-day period), Kruskal-Wallis (daily analysis for 7 days), univariate and multivariate logistic regression models. AUCs (CI 95%) were calculated and compared using DeLong's test. RESULTS: Average LLR over the first 7 days was above 60 mmHg in 48% of patients. %time with CPP < LLR could predict mortality (AUC 0.73, p = < 0.001). This association becomes significant starting from the third day post injury. The relationship was maintained when correcting for IMPACT covariates or for high ICP. CONCLUSIONS: Using a multicentre cohort, we confirmed that CPP below LLR was associated with mortality during the first seven days post injury.
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Lesiones Traumáticas del Encéfalo , Circulación Cerebrovascular , Humanos , Estudios Retrospectivos , Modelos Logísticos , Área Bajo la Curva , Presión IntracranealRESUMEN
BACKGROUND: Monitoring intracranial pressure (ICP) and cerebral perfusion pressure (CPP) is crucial in the management of the patient with severe traumatic brain injury (TBI). In several institutions ICP and CPP are summarized hourly and entered manually on bedside charts; these data have been used in large observational and interventional trials. However, ICP and CPP may change rapidly and frequently, so data recorded in medical charts might underestimate actual ICP and CPP shifts. The aim of this study was to evaluate the accuracy of manual data annotation for proper capturing of ICP and CPP. For this aim, we (1) compared end-hour ICP and CPP values manually recorded (MR) with values recorded continuously by computerized high-resolution (HR) systems and (2) analyzed whether MR ICP and MR CPP are reliable indicators of the burden of intracranial hypertension and low CPP. METHODS: One hundred patients were included. First, we compared the MR data with the values stored in the computerized system during the first 7 days after admission. For this point-to-point analysis, we calculated the difference between end-hour MR and HR ICP and CPP. Then we analyzed the burden of high ICP (> 20 mm Hg) and low CPP (< 60 mm Hg) measured by the computerized system, in which continuous data were stored, compared with the pressure-time dose based on end-hour measurements. RESULTS: The mean difference between MR and HR end-hour values was 0.02 mm Hg for ICP (SD 3.86 mm Hg) and 1.54 mm Hg for CPP (SD 8.81 mm Hg). ICP > 20 mm Hg and CPP < 60 mm Hg were not detected by MR in 1.6% and 5.8% of synchronized measurements, respectively. Analysis of the pathological ICP and CPP throughout the recording, however, indicated that calculations based on manual recording seriously underestimated the ICP and CPP burden (in 42% and 28% of patients, respectively). CONCLUSIONS: Manual entries fairly represent end-hour HR ICP and CPP. However, compared with a computerized system, they may prove inadequate, with a serious risk of underestimation of the ICP and CPP burden.
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Lesiones Traumáticas del Encéfalo , Lesiones Encefálicas , Hipertensión Intracraneal , Humanos , Lesiones Traumáticas del Encéfalo/diagnóstico , Circulación Cerebrovascular , Hospitalización , Hipertensión Intracraneal/diagnóstico , Presión IntracranealRESUMEN
PURPOSE: CPPopt denotes a Cerebral Perfusion Pressure (CPP) value at which the Pressure-Reactivity index, reflecting the global state of Cerebral Autoregulation, is best preserved. CPPopt has been investigated as a potential dynamically individualised CPP target in traumatic brain injury patients admitted in intensive care unit. The prospective bedside use of the concept requires ensured safety and reliability of the CPP recommended targets based on the automatically-generated CPPopt. We aimed to: Increase stability and reliability of the CPPopt automated algorithm by fine-tuning; perform outcome validation of the adjusted algorithm in a multi-centre TBI cohort. METHODS: ICM + software was used to derive CPPopt and fine-tune the algorithm. Parameters for improvement of the algorithm were selected based on qualitative and quantitative assessment of stability and reliability metrics. Patients enrolled in the Collaborative European Neuro Trauma Effectiveness Research in TBI (CENTER-TBI) high-resolution cohort were included for retrospective validation. Yield and stability of the new algorithm were compared to the previous algorithm using Mann-U test. Area under the curves for mortality prediction at 6 months were compared with the DeLong Test. RESULTS: CPPopt showed higher stability (p < 0.0001), but lower yield compared to the previous algorithm [80.5% (70-87.5) vs 85% (75.7-91.2), p < 0.001]. Deviation of CPPopt could predict mortality with an AUC of [AUC = 0.69 (95% CI 0.59-0.78), p < 0.001] and was comparable with the previous algorithm. CONCLUSION: The CPPopt calculation algorithm was fine-tuned and adapted for prospective use with acceptable lower yield, improved stability and maintained prognostic power.
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Lesiones Traumáticas del Encéfalo , Presión Intracraneal , Humanos , Estudios Retrospectivos , Reproducibilidad de los Resultados , Presión Intracraneal/fisiología , Circulación Cerebrovascular/fisiología , Lesiones Traumáticas del Encéfalo/terapia , Algoritmos , Homeostasis/fisiologíaRESUMEN
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 (ctnp), as well as two additional brain-heart crosstalks indicators [mutual information ([Formula: see text]) and average edge overlap (ωct)] 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 ctnp and 0.006 for ωct). An inverse correlation was found, computed using the point biserial correlation technique, between the three new measures and mortality: - 0.13 for ctnp (p value 0.04), - 0.19 for ωct (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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Lesiones Traumáticas del Encéfalo/fisiopatología , Encéfalo/fisiopatología , Frecuencia Cardíaca/fisiología , Corazón/fisiología , Presión Intracraneal/fisiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Encéfalo/diagnóstico por imagen , Lesiones Traumáticas del Encéfalo/mortalidad , Estudios de Cohortes , Humanos , Persona de Mediana Edad , Monitoreo Fisiológico , Adulto JovenRESUMEN
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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Lesiones Traumáticas del Encéfalo , Lenguajes de Programación , Humanos , Programas InformáticosRESUMEN
INTRODUCTION: Cerebrovascular impedance describes the relationship between pulsatile changes in arterial blood pressure (ABP) and cerebral blood flow (CBF). It is commonly defined by modulus and phase shift derived from Fourier spectra of ABP and CBF velocity (CBFV) signals under mostly steady-state conditions. The aim of this work was to assess heartbeat-to-heartbeat cerebrovascular impedance at heart rate frequency during controlled changes in mean ABP and intracranial pressure (ICP). MATERIAL AND METHODS: Recordings of ABP in the femoral artery, transcranial Doppler CBFV in the basilar artery, and subarachnoid ICP were obtained from anesthetized rabbits with induced arterial hypotension (n = 8 rabbits), arterial hypertension (n = 5), or intracranial hypertension (n = 7). Modulus of cerebrovascular impedance (|Z|) was estimated from amplitudes of ABP and CBFV. Phase shift of cerebrovascular impedance (PS) was estimated from time-frequency (TF) representations of phase shift between ABP and CBFV overlaid with a time-variant mask based on the fundamental frequency of ABP. RESULTS: Both |Z| and PS increased with increasing mean ABP. |Z| decreased with increasing mean ICP, but no change was observed in PS. CONCLUSIONS: The combined beat-to-beat and TF approach allows for the estimation of cerebrovascular impedance during transient hemodynamic changes. |Z| and PS follow the pattern of changes in CPP.
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Impedancia Eléctrica , Presión Intracraneal , Animales , Velocidad del Flujo Sanguíneo , Presión Sanguínea , Circulación Cerebrovascular , Proyectos Piloto , Conejos , Ultrasonografía Doppler TranscranealRESUMEN
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 (CCSF), (b) based on the evaluation of changes in cerebral arterial blood volume (CCaBV), and (c) based on the amplitudes of peaks P1 and P2 of ICP pulse waveform (CP1/P2). RESULTS: Increase in ICP caused a significant decrease in all compliance estimates (p < 0.0001). Time courses of compliance estimators were strongly positively correlated with each other (group-averaged Spearman correlation coefficients: 0.94 [0.88-0.97] for CCSF vs. CCaBV, 0.77 [0.63-0.91] for CCSF vs. CP1/P2, and 0.68 [0.48-0.91] for CCaBV vs. CP1/P2). CONCLUSIONS: Indirect methods, CCaBV and CP1/P2, allow for the assessment of relative changes in cerebrospinal compliance and produce results exhibiting good correlation with the direct method of volumetric manipulation. This opens the possibility of monitoring relative changes in compliance continuously.
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Encéfalo , Circulación Cerebrovascular , Columna Vertebral , Velocidad del Flujo Sanguíneo , Humanos , Hidrocéfalo Normotenso , Presión Intracraneal , Estudios RetrospectivosRESUMEN
BACKGROUND: The pulse waveform of intracranial pressure (ICP) is its distinctive feature almost always present in the clinical recordings. In most cases, it changes proportionally to rising ICP, and observation of these changes may be clinically useful. We introduce the higher harmonics centroid (HHC) which can be defined as the center of mass of harmonics of the ICP pulse waveform from the 2nd to 10th, where mass corresponds to amplitudes of these harmonics. We investigate the changes in HHC during ICP monitoring, including isolated episodes of ICP plateau waves. MATERIAL AND METHODS: Recordings from 325 patients treated between 2002 and 2010 were reviewed. Twenty-six patients with ICP plateau waves were identified. In the first step, the correlation between HHC and ICP was examined for the entire monitoring period. In the second step, the above relation was calculated separately for periods of elevated ICP during plateau wave and the baseline. RESULTS: For the values averaged over the whole monitoring period, ICP (22.3 ± 6.9 mm Hg) correlates significantly (R = 0.45, p = 0.022) with HHC (3.64 ± 0.46). During the ICP plateau waves (ICP increased from 20.9 ± 6.0 to 53.7 ± 9.7 mm Hg, p < 10-16), we found a significant decrease in HHC (from 3.65 ± 0.48 to 3.21 ± 0.33, p = 10-5). CONCLUSIONS: The good correlation between HHC and ICP supports the clinical application of pressure waveform analysis in addition to the recording of ICP number only. Mean ICP may be distorted by a zero drift, but HHC remains immune to this error. Further research is required to test whether a decline in HHC with elevated ICP can be an early warning sign of intracranial hypertension, whether individual breakpoints of correlation between ICP and its centroid are of clinical importance.
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Hipertensión Intracraneal , Presión Intracraneal , Presión Sanguínea , Frecuencia Cardíaca , Humanos , Hipertensión Intracraneal/diagnóstico , Monitoreo FisiológicoRESUMEN
PURPOSE: To ascertain whether changes in the spectral content of the corneal pulse (CP) signal, measured in vivo in primary open-angle glaucoma (POAG) patients, indirectly reflect changes in corneal biomechanics after canaloplasty. METHODS: Fifteen eyes of 15 POAG patients who underwent canaloplasty combined with phacoemulsification were enrolled. Standard ophthalmic examinations were conducted before washout, pre-operatively, at days 1, 7, and 1, 3, 6, and 12 months after surgery. Non-contact measurements of the CP signal were performed at pre-washout, pre-operatively, and at 3, 6, and 12 months post-operatively. Then, amplitudes of the CP first five harmonics associated with the heart rate were estimated. Temporal changes of all considered parameters were tested at a Bonferroni-adjusted significance level set to 0.005. RESULTS: A decrease in the amplitude of the first harmonic and an increase in the normalized amplitude of the third harmonic (ACP3n) of the CP signal were noticed between the pre-washout and the pre-operative stages (p = 0.003 and p = 0.004, respectively). This corresponds to an increase in median intraocular pressure (IOP) values by 6.0 mmHg (p = 0.0045). After surgery, ACP3n reached the highest value at 3 months post-operatively, compared with pre-washout level (p = 0.0045). CONCLUSIONS: Alterations in corneoscleral stiffness caused by surgery are reflected in changes in the ACP3n value. Hence, post-operative corneal biomechanics could be monitored indirectly by this supporting indicator that can be used to estimate the time at which measures of IOP are no longer biased by the changed cornea boundary conditions caused by canaloplasty. CLINICAL TRIALS REGISTRATION: NCT02908633.
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Córnea/fisiopatología , Cirugía Filtrante/métodos , Glaucoma de Ángulo Abierto/fisiopatología , Presión Intraocular/fisiología , Agudeza Visual , Anciano , Anciano de 80 o más Años , Fenómenos Biomecánicos , Córnea/diagnóstico por imagen , Femenino , Glaucoma de Ángulo Abierto/diagnóstico , Glaucoma de Ángulo Abierto/cirugía , Humanos , Masculino , Persona de Mediana Edad , Periodo PosoperatorioRESUMEN
Introduction: Cerebrospinal fluid (CSF) infusion test analysis allows recognizing and appropriately evaluating CSF dynamics in the context of normal pressure hydrocephalus (NPH), which is crucial for effective diagnosis and treatment. However, existing methodology possesses drawbacks that may compromise the precision and interpretation of CSF dynamics parameters. Research question: This study aims to circumvent these constraints by introducing an innovative analysis method grounded in Bayesian inference. Material and methods: A single-centre retrospective cohort study was conducted on 858 patients who underwent a computerized CSF infusion test between 2004 and 2020. We developed a Bayesian framework-based method for parameter estimation and compared the results to the current, gradient descent-based approach. We evaluated the accuracy and reliability of both methods by analysing erroneous prediction rates and curve fitting errors. Results: The Bayesian method surpasses the gradient descent approach, reflected in reduced inaccurate prediction rates and an improved goodness of model fit. On whole cohort level both techniques produced comparable results. However, the Bayesian method holds an added advantage by providing uncertainty intervals for each parameter. Sensitivity analysis revealed significance of the CSF production rate parameter and its interplay with other variables. The resistance to CSF outflow demonstrated excellent robustness. Discussion and conclusion: The proposed Bayesian approach offers a promising solution for improving robustness of CSF dynamics assessment in NPH, based on CSF infusion tests. Additional provision of the uncertainty measure for each diagnostic metric may perhaps help to explain occasional poor diagnostic performance of the test, offering a robust framework for improved understanding and management of NPH.
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Introduction: Cerebral autoregulation (CA) dysfunction is a key complication following brain injury. CA assessment using near-infrared spectroscopy (NIRS) offers a promising alternative to the current non-invasive standard, cerebral blood flow velocity (CBFV) measured with transcranial Doppler. Research question: Can autoregulatory slow waves (frequency range 0.005-0.05 Hz) associated with spontaneous and induced changes in ABP in healthy volunteers be detected by parameters measured with the Masimo O3 NIRS device? Methods: ABP, CBFV and Masimo O3 parameters were measured in 10 healthy volunteers at baseline and during ABP oscillations induced by squat/stand manoeuvres. Transmission of slow waves was assessed with power spectral density and coherence analysis in NIRS signals and compared to that of CBFV. Results: At baseline, slow waves were detected with sufficient power that substantially exceeded the signals' measurement resolution in all parameters except cerebral oxygen saturation. During ABP oscillations in the 0.033 Hz range (induced by squat/stand), the power of slow waves increased in all parameters in a similar pattern, with total (cHb) and oxygenated (O2Hb) haemoglobin concentrations most closely mirroring CBFV (median standardised power [first-third quartile], baseline vs squat/stand: CBFV 0.35 [0.28-0.42] vs 0.50 [0.45-0.62], O2Hb 0.47 [0.33-0.68] vs 0.61 [0.59-0.69]). Coherence with ABP increased for both CBFV and NIRS measures from low at baseline (<0.4) to high during induced changes (>0.8). Conclusion: Spontaneous fluctuations in ABP can be observed in analysed Masimo O3 metrics to a varying degree. The clinical utility of Masimo O3 signals in CA assessment requires further investigation in brain injury patients.
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Introduction: PRx can be used as surrogate measure of Cerebral Autoregulation (CA) in traumatic brain injury (TBI) patients. PRx can provide means for individualising cerebral perfusion pressure (CPP) targets, such as CPPopt. However, a recent Delphi consensus of clinicians concluded that consensus could not be reached on the accuracy, reliability, and validation of any current CA assessment method. Research question: We aimed to quantify the short-term uncertainty of PRx time-trends and to relate this to other physiological measurements. Material and methods: Intracranial pressure (ICP), arterial blood pressure (ABP), end-tidal CO2 (EtCO2) high-resolution recordings of 911 TBI patients were processed with ICM + software. Hourly values of metrics that describe the variability within modalities derived from ABP, ICP and EtCO2, were calculated for the first 24h of neuromonitoring. Generalized additive models were used to describe the time trend of the variability in PRx. Linear correlations were studied for describing the relationship between PRx variability and the other physiological modalities. Results: The time profile of variability of PRx decreases over the first 12h and was higher for average PRx â¼0. Increased variability of PRx was not linearly linked with average ABP, ICP, or CPP. For coherence between slow waves of ABP and ICP >0.7, the variability in PRx decreased (R = -0.47, p < 0.001). Discussion and conclusion: PRx is a highly variable parameter. PRx short-term dispersion was not related to average ICP, ABP or CPP. The determinants of uncertainty of PRx should be investigated to improve reliability of individualised CA assessment in TBI patients.
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Introduction: Continuous monitoring of the pressure reactivity index (PRx) provides an estimation of dynamic cerebral autoregulation (CA) at the bedside in traumatic brain injury (TBI) patients. Visualising the time-trend of PRx with a risk bar chart in ICM + software at the bedside allows for better real-time interpretability of the autoregulation status. When PRx>0.3 is sustained for long periods, typically of at least half an hour, the bar shows a pattern called "red solid line" (RSL). RSL was previously described to precede refractory intracranial hypertension and brain death. Research question: We aimed to describe pathophysiological changes in measured signals/parameters during RSL. Material and methods: Observation of time-trends of PRx, intracranial pressure, cerebral perfusion pressure, brain oxygenation and compensatory reserve of TBI patients with RSL. Results: Three pathophysiological patterns were identified: RSL precedes intracranial hypertension, RSL is preceded by intracranial hypertension, or RSL is preceded by brain hypoperfusion. In all cases, RSL was followed by death and the RSL onset was between 1 h and 1 day before the terminal event. Discussion and conclusion: RSL precedes death in intensive care and could represent a marker for terminal clinical deterioration in TBI patients. These findings warrant further investigations in larger cohorts to characterise pathophysiological mechanisms underlying the RSL pattern and whether RSL has a significant relationship with outcome after TBI.
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INTRODUCTION: Studying cerebral autoregulation, particularly PRx (Pressure Reactivity Index), is commonly employed in adult traumatic brain injury (TBI) and gives real-time information about intracranial pathophysiology, which can help in patient management. Experience in paediatric TBI (PTBI) is limited to single-centre studies despite disproportionately higher incidence of morbidity and mortality in PTBI than in adult TBI. PROJECT: We describe the protocol to study cerebral autoregulation using PRx in PTBI. The project called Studying Trends of Auto-Regulation in Severe Head Injury in Paediatrics is a multicentre prospective ethics approved research database study from 10 centres across the UK. Recruitment started in July 2018 with financial support from local/national charities (Action Medical Research for Children, UK). METHODS AND ANALYSIS: The first phase of the project is powered to detect optimal thresholds of PRx associated with favourable outcome in PTBI by recruiting 135 patients (initial target of 3 years which has changed to 5 years due to delays related to COVID-19 pandemic) from 10 centres in the UK with outcome follow-up to 1-year postictus. The secondary objectives are to characterise patterns of optimal cerebral perfusion pressure in PTBI and compare the fluctuations in these measured parameters with outcome. The goal is to create a comprehensive research database of a basic set of high-resolution (full waveforms resolution) neuromonitoring data in PTBI for scientific use. ETHICS AND DISSEMINATION: Favourable ethical approval has been provided by Health Research Authority, Southwest-Central Bristol Research Ethics Committee (Ref: 18/SW/0053). Results will be disseminated via publications in peer-reviewed medical journals and presentations at national and international conferences. TRIAL REGISTRATION NUMBER: NCT05688462.
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Lesiones Traumáticas del Encéfalo , COVID-19 , Adulto , Niño , Humanos , Lesiones Traumáticas del Encéfalo/complicaciones , Circulación Cerebrovascular/fisiología , COVID-19/complicaciones , Homeostasis/fisiología , Presión Intracraneal/fisiología , Estudios Multicéntricos como Asunto , Estudios Observacionales como Asunto , Pandemias , Estudios ProspectivosRESUMEN
Introduction: Disturbance in cerebrospinal fluid (CSF) circulation may overlap with abnormality of cerebral blood flow (CBF) in hydrocephalus. Transcranial Doppler (TCD) ultrasonography is a non-invasive technique able to assess CBF velocity (CBFv) dynamics in response to a controlled rise in ICP during CSF infusion tests. Research question: Which TCD-derived cerebral hemodynamic parameters change during controlled rise of ICP, and in which direction? Material and methods: Infusion tests combined with TCD monitoring and non-invasive monitoring of arterial blood pressure (ABP) were conducted in 65 hydrocephalic patients. TCD-based hemodynamic variables: spectral pulsatility index (sPI), compliance of CSF space (Ci), cerebral autoregulation index (Mx), critical closing pressure (CrCP), cerebrovascular wall tension (WT) and diastolic closing margin (DCM-distance between diastolic ABP and CrCP) were calculated retrospectively. Results: During the test ICP increased on average to 25 mm Hg (p < 0.0001), with a parallel decrease in cerebral perfusion pressure (CPP, p < 0.0003). The CBFv waveform changed, showing a rise in sPI (p < 0.0001). Ci decreased inversely proportional to a rise in ICP, and correlated well with changes of compliance calculated from the Marmarou model. CrCP increased in response to rising ICP (p < 0.001) while WT decreased (p < 0.002). DCM correlated with cerebrospinal elasticity (R = -0.31; p < 0.04). Cerebral autoregulation was worse in patients with normal CSF circulation, measured as resistance to CSF outflow (Rout): Pearson correlation between Mx and Rout was R = -0.41; p < 0.02. Conclusion: A controlled rise in ICP affects cerebral hemodynamics in a moderate manner. Parameters like cerebral autoregulation index or DCM correlate with CSF dynamics and may be considered as supplementary variables for the diagnosis of hydrocephalus.
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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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A reliable method for non-invasive detection of dangerous intracranial pressure (ICP) elevations is still unavailable. In this preliminary study, we investigate quantitatively our observation that superimposing waveforms of transcranial Doppler blood flow velocity (FV) and arterial blood pressure (ABP) may help in non-invasive identification of ICP plateau waves. Recordings of FV, ABP and ICP in 160 patients with severe head injury (treated in the Neurocritical Care Unit at Addenbrookes Hospital, Cambridge, UK) were reviewed retrospectively. From that cohort, we identified 18 plateau waves registered in eight patients. A "measure of dissimilarity" (Dissimilarity/Difference Index, DI) between ABP and FV waveforms was calculated in three following steps: 1. fragmentation of ABP and FV signal according to cardiac cycle; 2. obtaining the normalised representative ABP and FV cycles; and finally; 3. assessing their difference, represented by the area between both curves. DI appeared to discriminate ICP plateau waves from baseline episodes slightly better than conventional pulsatility index did: area under ROC curve 0.92 vs. 0.90, sensitivity 0.81 vs. 0.69, accuracy 0.88 vs. 0.84, respectively. The concept of DI, if further tested and improved, might be used for non-invasive detection of ICP plateau waves.
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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.