Update in intracranial pressure evaluation methods and translaminar pressure gradient role in glaucoma

Glaucoma is one of the leading causes of blindness worldwide. Historically, it has been considered an ocular disease primary caused by pathological intraocular pressure (IOP). Recently, researchers have emphasized intracranial pressure (ICP), as translaminar counter pressure against IOP may play a role in glaucoma development and progression. It remains controversial what is the best way to measure ICP in glaucoma. Currently, the ‘gold standard’ for ICP measurement is invasive measurement of the pressure in the cerebrospinal fluid via lumbar puncture or via implantation of the pressure sensor into the brains ventricle. However, the direct measurements of ICP are not without risk due to its invasiveness and potential risk of intracranial haemorrhage and infection. Therefore, invasive ICP measurements are prohibitive due to safety needs, especially in glaucoma patients. Several approaches have been proposed to estimate ICP non-invasively, including transcranial Doppler ultrasonography, tympanic membrane displacement, ophthalmodynamometry, measurement of optic nerve sheath diameter and two-depth transcranial Doppler technology. Special emphasis is put on the two-depth transcranial Doppler technology, which uses an ophthalmic artery as a natural ICP sensor. It is the only method which accurately and precisely measures absolute ICP values and may provide valuable information in glaucoma

The Difference in Translaminar Pressure Gradient and Neuroretinal Rim Area in Glaucoma and Healthy Subjects

Purpose. To assess differences in translaminar pressure gradient (TPG) and neuroretinal rim area (NRA) in patients with normal tension glaucoma (NTG), high tension glaucoma (HTG), and healthy controls. Methods. 27 patients with NTG, HTG, and healthy controls were included in the prospective pilot study (each group consisted of 9 patients). Intraocular pressure (IOP), intracranial pressure (ICP), and confocal laser scanning tomography were assessed. TPG was calculated as the difference of IOP minus ICP. ICP was measured using noninvasive two-depth transcranial Doppler device. The level of significance P < 0.05 was considered significant. Results. NTG patients had significantly lower IOP (13.7(1.6) mmHg), NRA (0.97(0.36) mm2), comparing with HTG and healthy subjects, P < 0.05. ICP was lower in NTG (7.4(2.7) mmHg), compared with HTG (8.9(1.9) mmHg) and healthy subjects (10.5(3.0) mmHg); however, the difference between groups was not statistically significant (P>0.05). The difference between TPG for healthy (5.4(7.7) mmHg) and glaucomatous eyes (NTG 6.3(3.1) mmHg, HTG 15.7(7.7) mmHg) was statistically significant (P < 0.001). Higher TPG was correlated with decreased NRA (r = −0.83; P = 0.01) in the NTG group. Conclusion. Translaminar pressure gradient was higher in glaucoma patients. Reduction of NRA was related to higher TPG in NTG patients. Further prospective studies are warranted to investigate the involvement of TPG in glaucoma management

Method for Prediction of Acute Hypotensive Episodes

Hypotension is type of secondary insult and it is related to poor outcome. The ability to predict adverse hypotensive events, where a patient's arterial blood pressure drops to abnormally low levels, would be of major benefit to the fields of primary and secondary health care. The aim of the paper is to present the novel method for predicting of acute hypotensive episodes, based on ECG analysis by the complex system theory approach. 45 patients (in four neurointensive care facilities throughout Europe) data were selected for the analysis. 11 patients had EUSIG-defined hypotensive events. The method includes determining of time varying biomarkers corresponding to plurality of physiological processes in patient's organism as a non-linear dynamic complex system and generating an acute hypotension prediction classifier. The calculations of biomarkers are based on complex system approach and algebraic matrix analysis of ECG parameters. The classifier is based on the comparison of biomarkers behaviour in 3D images. It is demonstrated that the presented method allows us to predict arterial hypotension events 40-50 minutes ahead with a sensitivity of 81 %, specificity 94 %. This result was obtained from prospective real-time data collection in a live clinical intensive care environment

The Brain Monitoring with Information Technology (BrainIT) collaborative network:: Past, Present and Future Direction

The BrainIT group works collaboratively on developing standards for collection and analyses of&nbsp;data from brain injured patients and to facilitate a more efficient infrastructure for assessing new&nbsp;health care technology with the primary objective of improving patient care. European&nbsp;Community funding supported meetings over a year to discuss and define a core dataset to be&nbsp;collected from patients with traumatic brain injury using IT based methods. In this paper, we&nbsp;give an overview of the aims and future directions of the group as well as present the results of&nbsp;an EC funded study with the aim of testing the feasibility of collecting this core dataset across a&nbsp;number of European sites and discuss the future direction of this research network. Over a three&nbsp;year period, data collection client and web-server based tools were developed and core data&nbsp;(grouped into 9 categories) were collected from 200 head-injured patients by local nursing staff&nbsp;in 22 European neuro-intensive care centres. Data were uploaded through the BrainIT web site&nbsp;and random samples of received data were selected automatically by computer for validation by&nbsp;data validation (DV) staff against primary sources held in each local centre. Validated data were&nbsp;compared with originally transmitted data and percentage error rates calculated by data category.&nbsp;Feasibility was assessed in terms of the proportion of missing data, accuracy of data collected andlimitations reported by users of the IT methods. Thirteen percent of data files required cleaning.&nbsp;Thirty “one-off” demographic and clinical data elements had significant amounts of missing data&nbsp;(&gt; 15%). Validation staff conducted 19,461 comparisons between uploaded database data with&nbsp;local data sources and error rates were commonly less than or equal to 6%, the exception being&nbsp;the surgery data class where an unacceptably high error rate of 34% was found. Nearly 10,000therapies were successfully recorded with start-times but approximately a third had inaccurate or&nbsp;missing end times which limits the analysis of duration of therapy. Over 40,000 events and&nbsp;procedures were recorded but events with long durations (such as transfers) were more likely to&nbsp;have “end-times” missed. The BrainIT core dataset is a rich dataset for hypothesis generation&nbsp;and post-hoc analyses provided studies avoid known limitations in the dataset. Limitations in the&nbsp;current IT based data collection tools have been identified and have been addressed. In order for&nbsp;multi-centre data collection projects to be viable the resource intensive validation procedures&nbsp;will require a more automated process and this may include direct electronic access to hospital&nbsp;based clinical data sources for both validation purposes and for minimising the duplication of&nbsp;data entry. This type of infrastructure may foster and facilitate the remote monitoring of patient&nbsp;management and protocol adherence in future trials of patient management and monitoring.&nbsp

Low-resolution pressure reactivity index and its derived optimal cerebral perfusion pressure in adult traumatic brain injury: a CENTER-TBI study

Abstract: Background: After traumatic brain injury (TBI), brain tissue can be further damaged when cerebral autoregulation is impaired. Managing cerebral perfusion pressure (CPP) according to computed “optimal CPP” values based on cerebrovascular reactivity indices might contribute to preventing such secondary injuries. In this study, we examined the discriminative value of a low-resolution long pressure reactivity index (LPRx) and its derived “optimal CPP” in comparison to the well-established high-resolution pressure reactivity index (PRx). Methods: Using the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study dataset, the association of LPRx (correlation between 1-min averages of intracranial pressure and arterial blood pressure over a moving time frame of 20 min) and PRx (correlation between 10-s averages of intracranial pressure and arterial blood pressure over a moving time frame of 5 min) to outcome was assessed and compared using univariate and multivariate regression analysis. “Optimal CPP” values were calculated using a multi-window algorithm that was based on either LPRx or PRx, and their discriminative ability was compared. Results: LPRx and PRx were both significant predictors of mortality in univariate and multivariate regression analysis, but PRx displayed a higher discriminative ability. Similarly, deviations of actual CPP from “optimal CPP” values calculated from each index were significantly associated with outcome in univariate and multivariate analysis. “Optimal CPP” based on PRx, however, trended towards more precise predictions. Conclusions: LPRx and its derived “optimal CPP” which are based on low-resolution data were significantly associated with outcome after TBI. However, they did not reach the discriminative ability of the high-resolution PRx and its derived “optimal CPP.” Nevertheless, LPRx might still be an interesting tool to assess cerebrovascular reactivity in centers without high-resolution signal monitoring. Trial registration: ClinicalTrials.gov Identifier: NCT02210221. First submitted July 29, 2014. First posted August 6, 2014

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

Abstract: 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

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

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

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

Funder: University of CambridgeAbstract: 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

Abstract: 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

Quality indicators for patients with traumatic brain injury in European intensive care units

Background: The aim of this study is to validate a previously published consensus-based quality indicator set for the management of patients with traumatic brain injury (TBI) at intensive care units (ICUs) in Europe and to study its potential for quality measur