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

Background To date, the cerebral physiologic consequences of persistently elevated intracranial pressure (ICP) have been based on either low-resolution physiologic data or retrospective high-frequency data from single centers. The goal of this study was to provide a descriptive multi-center analysis of the cerebral physiologic consequences of ICP, comparing those with normal ICP to those with elevated ICP. Methods The Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) High-Resolution Intensive Care Unit (HR-ICU) sub-study cohort was utilized. The first 3 days of physiologic recording were analyzed, evaluating and comparing those patients with mean ICP 20 mmHg. Various cerebral physiologic parameters were derived and evaluated, including ICP, brain tissue oxygen (PbtO(2)), cerebral perfusion pressure (CPP), pulse amplitude of ICP (AMP), cerebrovascular reactivity, and cerebral compensatory reserve. The percentage time and dose above/below thresholds were also assessed. Basic descriptive statistics were employed in comparing the two cohorts. Results 185 patients were included, with 157 displaying a mean ICP below 15 mmHg and 28 having a mean ICP above 20 mmHg. For admission demographics, only admission Marshall and Rotterdam CT scores were statistically different between groups (p = 0.017 andp = 0.030, respectively). The high ICP group displayed statistically worse CPP, PbtO(2), cerebrovascular reactivity, and compensatory reserve. The high ICP group displayed worse 6-month mortality (p <0.0001) and poor outcome (p = 0.014), based on the Extended Glasgow Outcome Score. Conclusions Low versus high ICP during the first 72 h after moderate/severe TBI is associated with significant disparities in CPP, AMP, cerebrovascular reactivity, cerebral compensatory reserve, and brain tissue oxygenation metrics. Such ICP extremes appear to be strongly related to 6-month patient outcomes, in keeping with previous literature. This work provides multi-center validation for previously described single-center retrospective results.Peer reviewe

Wavelet pressure reactivity index: a validation study.

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

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

BACKGROUND: Monitoring cerebrovascular reactivity in adult traumatic brain injury (TBI) has been linked to global patient outcome. Three intra-cranial pressure (ICP)-derived indices have been described. It is unknown which index is superior for outcome association in TBI outside previous single-center evaluations. The goal of this study is to evaluate indices for 6- to 12-month outcome association using uniform data harvested in multiple centers. METHODS: Using the prospectively collected data from the Collaborative European NeuroTrauma Effectiveness Research in TBI (CENTER-TBI) study, the following indices of cerebrovascular reactivity were derived: PRx (correlation between ICP and mean arterial pressure (MAP)), PAx (correlation between pulse amplitude of ICP (AMP) and MAP), and RAC (correlation between AMP and cerebral perfusion pressure (CPP)). Univariate logistic regression models were created to assess the association between vascular reactivity indices with global dichotomized outcome at 6 to 12 months, as assessed by Glasgow Outcome Score-Extended (GOSE). Models were compared via area under the receiver operating curve (AUC) and Delong's test. RESULTS: Two separate patient groups from this cohort were assessed: the total population with available data (n = 204) and only those without decompressive craniectomy (n = 159), with identical results. PRx, PAx, and RAC perform similar in outcome association for both dichotomized outcomes, alive/dead and favorable/unfavorable, with RAC trending towards higher AUC values. There were statistically higher mean values for the index, % time above threshold, and hourly dose above threshold for each of PRx, PAx, and RAC in those patients with poor outcomes. CONCLUSIONS: PRx, PAx, and RAC appear similar in their associations with 6- to 12-month outcome in moderate/severe adult TBI, with RAC showing tendency to achieve stronger associations. Further work is required to determine the role for each of these cerebrovascular indices in monitoring of TBI patients.Data used in preparation of this manuscript were obtained in the context of CENTER-TBI, a large collaborative project with the support of the European Union 7th Framework program (EC grant 602150). Additional funding was obtained from the Hannelore Kohl Stiftung (Germany), from OneMind (USA) and from Integra LifeSciences Corporation (USA).DKM was also supported by funding from the National Institute for Health Research (NIHR, UK) through a Senior Investigator award and the Cambridge Biomedical Research Centre at the Cambridge University Hospitals NHS Foundation Trust. The study also received additional support from the NIHR Clinical Research network. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care, UK. FAZ has received salary support for dedicated research time, during which this project was completed. Such salary support came from: the Cambridge Commonwealth Trust Scholarship, the University of Manitoba Clinician Investigator Program, and the Royal College of Surgeons of Canada – Harry S. Morton Travelling Fellowship in Surgery

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

Export Date: 16 February 2023; Cited By: 7Peer reviewe

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

BACKGROUND: To date, the cerebral physiologic consequences of persistently elevated intracranial pressure (ICP) have been based on either low-resolution physiologic data or retrospective high-frequency data from single centers. The goal of this study was to provide a descriptive multi-center analysis of the cerebral physiologic consequences of ICP, comparing those with normal ICP to those with elevated ICP. METHODS: The Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) High-Resolution Intensive Care Unit (HR-ICU) sub-study cohort was utilized. The first 3 days of physiologic recording were analyzed, evaluating and comparing those patients with mean ICP  20 mmHg. Various cerebral physiologic parameters were derived and evaluated, including ICP, brain tissue oxygen (PbtO2), cerebral perfusion pressure (CPP), pulse amplitude of ICP (AMP), cerebrovascular reactivity, and cerebral compensatory reserve. The percentage time and dose above/below thresholds were also assessed. Basic descriptive statistics were employed in comparing the two cohorts. RESULTS: 185 patients were included, with 157 displaying a mean ICP below 15 mmHg and 28 having a mean ICP above 20 mmHg. For admission demographics, only admission Marshall and Rotterdam CT scores were statistically different between groups (p = 0.017 and p = 0.030, respectively). The high ICP group displayed statistically worse CPP, PbtO2, cerebrovascular reactivity, and compensatory reserve. The high ICP group displayed worse 6-month mortality (p < 0.0001) and poor outcome (p = 0.014), based on the Extended Glasgow Outcome Score. CONCLUSIONS: Low versus high ICP during the first 72 h after moderate/severe TBI is associated with significant disparities in CPP, AMP, cerebrovascular reactivity, cerebral compensatory reserve, and brain tissue oxygenation metrics. Such ICP extremes appear to be strongly related to 6-month patient outcomes, in keeping with previous literature. This work provides multi-center validation for previously described single-center retrospective results

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

BACKGROUND: Impaired cerebrovascular reactivity in adult traumatic brain injury (TBI) is known to be associated with poor outcome. However, there has yet to be an analysis of the association between the comprehensively assessed intracranial hypertension therapeutic intensity level (TIL) and cerebrovascular reactivity. METHODS: Using the Collaborative European Neuro Trauma Effectiveness Research in TBI (CENTER-TBI) high-resolution intensive care unit (ICU) cohort, we derived pressure reactivity index (PRx) as the moving correlation coefficient between slow-wave in ICP and mean arterial pressure, updated every minute. Mean daily PRx, and daily % time above PRx of 0 were calculated for the first 7 days of injury and ICU stay. This data was linked with the daily TIL-Intermediate scores, including total and individual treatment sub-scores. Daily mean PRx variable values were compared for each TIL treatment score via mean, standard deviation, and the Mann U test (Bonferroni correction for multiple comparisons). General fixed effects and mixed effects models for total TIL versus PRx were created to display the relation between TIL and cerebrovascular reactivity. RESULTS: A total of 249 patients with 1230 ICU days of high frequency physiology matched with daily TIL, were assessed. Total TIL was unrelated to daily PRx. Most TIL sub-scores failed to display a significant relationship with the PRx variables. Mild hyperventilation (p < 0.0001), mild hypothermia (p = 0.0001), high levels of sedation for ICP control (p = 0.0001), and use vasopressors for CPP management (p < 0.0001) were found to be associated with only a modest decrease in mean daily PRx or % time with PRx above 0. CONCLUSIONS: Cerebrovascular reactivity remains relatively independent of intracranial hypertension therapeutic intensity, suggesting inadequacy of current TBI therapies in modulating impaired autoregulation. These findings support the need for investigation into the molecular mechanisms involved, or individualized physiologic targets (ICP, CPP, or Co2) in order to treat dysautoregulation actively.EU 7th Framewor

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

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

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

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

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

BackgroundTo date, the cerebral physiologic consequences of persistently elevated intracranial pressure (ICP) have been based on either low-resolution physiologic data or retrospective high-frequency data from single centers. The goal of this study was to provide a descriptive multi-center analysis of the cerebral physiologic consequences of ICP, comparing those with normal ICP to those with elevated ICP.MethodsThe Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) High-Resolution Intensive Care Unit (HR-ICU) sub-study cohort was utilized. The first 3 days of physiologic recording were analyzed, evaluating and comparing those patients with mean ICP  20 mmHg. Various cerebral physiologic parameters were derived and evaluated, including ICP, brain tissue oxygen (PbtO2), cerebral perfusion pressure (CPP), pulse amplitude of ICP (AMP), cerebrovascular reactivity, and cerebral compensatory reserve. The percentage time and dose above/below thresholds were also assessed. Basic descriptive statistics were employed in comparing the two cohorts.Results185 patients were included, with 157 displaying a mean ICP below 15 mmHg and 28 having a mean ICP above 20 mmHg. For admission demographics, only admission Marshall and Rotterdam CT scores were statistically different between groups (p = 0.017 and p = 0.030, respectively). The high ICP group displayed statistically worse CPP, PbtO2, cerebrovascular reactivity, and compensatory reserve. The high ICP group displayed worse 6-month mortality (p ConclusionsLow versus high ICP during the first 72 h after moderate/severe TBI is associated with significant disparities in CPP, AMP, cerebrovascular reactivity, cerebral compensatory reserve, and brain tissue oxygenation metrics. Such ICP extremes appear to be strongly related to 6-month patient outcomes, in keeping with previous literature. This work provides multi-center validation for previously described single-center retrospective results.</p

Prospective study on non-invasive assessment of ICP in head injured patients: comparison of four methods

Elevation of intracranial pressure (ICP) may occur in many diseases and therefore the ability to measure it non-invasively would be useful. Flow velocity signals from Transcranial Doppler (TCD) have been used to estimate ICP, however the relative accuracy of these methods is unclear. This study aimed to compare 4 previously described TCD-based methods with directly measured ICP in a prospective cohort of head injured patients. Non-invasive ICP (nICP) was obtained using the following methods: I) a mathematical “black-box” model based on interaction between TCD and ABP (nICP_BB); II) based on diastolic FV (nICP_FVd); III) based on critical closing pressure (nICP_CrCP) and IV) based on TCD-derived pulsatility index (nICP_PI). In time domain, for recordings including spontaneous changes in ICP greater than 7 mmHg, nICP_PI showed the best correlation with measured ICP (R=0.61). Considering every TCD recording as an independent event, nICP_BB generally showed to be the best estimator of measured ICP (R=0.39, p0.05). nICP_PI was not related to measured ICP using any of the above statistical indicators. We also introduced a new estimator (nICP_Av) based on the average of 3 methods (nICP_BB, nICP_FVd and nICP_CrCP), which overall presented improved statistical indicators (R=0.47, p<0.05; 95% CI=9.17 mmHg; AUC= 0.73, p<0.05). nICP_PI appeared to reflect changes in ICP in time most accurately. nICP_BB was the best estimator for ICP ‘as a number’. nICP_Av demonstrated to improve the accuracy of measured ICP estimation.DC is supported by a Cambridge Commonwealth, European & International Trust Scholarship, University of Cambridge. JD is supported by a Woolf Fisher Trust Scholarship. XL is supported by a Gates Cambridge Scholarship. GVV is supported by an A. G. Leventis Foundation Scholarship, and a Charter Studentship from St Edmund’s College, Cambridge. SM and GF are supported by the Pan-American Health Organization. DC and MC are partially supported by NIHR Brain Injury Healthcare Technology Co-operative, Cambridge, UK.This is the author accepted manuscript. The final version is available from Mary Ann Liebert via http://dx.doi.org/10.1089/neu.2015.413