Pressure Reactivity Index Values Research Articles

Individualized Autoregulation-Derived Cerebral Perfusion Targets in Aneurysmal Subarachnoid Hemorrhage: A New Therapeutic Avenue?

Background: Cerebral perfusion pressure (CPP) is an important target in aneurysmal subarachnoid hemorrhage (aSAH), but it does not take into account autoregulatory disturbances. The pressure reactivity index (PRx) and the CPP with the optimal PRx (CPPopt) are new variables that may capture these pathomechanisms. In this study, we investigated the effect on the outcome of certain combinations of CPP or ΔCPPopt (actual CPP-CPPopt) with the concurrent autoregulatory status (PRx) after aSAH. Methods: This observational study included 432 aSAH patients, treated in the neurointensive care unit, at Uppsala University Hospital, Sweden. Functional outcome (GOS-E) was assessed 1-year postictus. Heatmaps of the percentage of good monitoring time (%GMT) of PRx/CPP and PRx/ΔCPPopt combinations in relation to GOS-E were created to visualize the association between these variables and outcome. Results: In the heatmap of the %GMT of PRx/CPP, the combination of lower CPP with higher PRx values was more strongly associated with lower GOS-E. The tolerance for lower CPP values increased with lower PRx values until a threshold of -0.50. However, for decreasing PRx below -0.50, there was a gradual reduction in the tolerance for lower CPP. In the heatmap of the %GMT of PRx/ΔCPPopt, the combination of negative ΔCPPopt with higher PRx values was strongly associated with lower GOS-E. In particular, negative ΔCPPopt together with PRx above +0.50 correlated with worse outcomes. In addition, there was a transition toward an unfavorable outcome when PRx went below -0.50, particularly if ΔCPPopt was negative. Conclusions: The PRx levels influenced the association between CPP/ΔCPPopt and outcome. Thus, this variable could be used to individualize a safe CPP-/ΔCPPopt-range.

437 Pressure Reactivity Index (PRx) as a Predictor for Outcome in Severe Traumatic Brain Injury

INTRODUCTION: The pressure reactivity index (PRx) is a surrogate for vascular cerebral autoregulation that evaluates moving correlation coefficients between intracranial pressure (ICP) and mean arterial blood pressure (MAP). Ideal threshold PRx values for distinguishing between poor and good outcome in severe traumatic brain injury (sTBI) is unclear. METHODS: Retrospective evaluation of consecutive patients over a three-year period with sTBI and polytrauma who received continuous ICP, MAP, and PRx monitoring. Good outcome was defined as patients who upon hospital discharge had a modified Rankin score < 4 and were discharged to an acute rehabilitation facility or home. RESULTS: 36 patients received continuous monitoring. Nine patients were excluded for the following reasons: early palliative withdrawal, early death through multi-organ dysfunction not related to the sTBI, and continuous neuromonitoring < 24 hrs. Of the 27 patients evaluated, average PRx values for the good outcome group was 0.18 (+0.17) and 0.37 (+0.24) for the poor outcome group. Receiver operating characteristics (ROC) analysis showed that a PRx threshold value > 0.34 had the highest combined sensitivity and specificity for predicting poor outcome with an AUC (95% CI) = 0.775 (0.583-0.967). When dichotomized using ROC curve analysis, a threshold PRx value of greater than 0.34 was independently associated with higher odds of poor outcome (OR 18.63, 95% CI 1.17-297.21, p = 0.038) after adjustment for potential confounders. CONCLUSIONS: Higher mean PRx is an independent predictor for poor outcome in patients with sTBI. Further study is required to evaluate the temporal role of PRx changes to improve neuroprognostication.

Variations in Autoregulation-Based Optimal Cerebral Perfusion Pressure Determination Using Two Integrated Neuromonitoring Platforms in a Trauma Patient.

Neuromonitoring devices are often used in traumatic brain injury.The objective of this report is to raise awareness concerning variations in optimal cerebral perfusion pressure (CPPopt) determination using exploratory information provided by two neuromonitoring monitors that are part of research programs (Moberg CNS Monitor and RAUMED NeuroSmart LogO). We connected both monitors simultaneously to a parenchymal intracranial pressure catheter and recorded the pressure reactivity index (PRx) and the derived CPPopt estimates for a patient with a severe traumatic brain injury. These estimates were available at the bedside and were updated at each minute. Using the Bland and Altman method, we found a mean variation of - 3.8 (95% confidence internal from - 8.5 to 0.9) mm Hg between the CPPopt estimates provided by the two monitors (limits of agreement from - 26.6 to 19.1mm Hg). The PRx and CPPopt trends provided by the two monitors were similar over time, but CPPopt trends differed when PRx values were around zero. Also, almost half of the CPPopt estimates differed by more than 10mm Hg. These wide variations recorded in the same patient are worrisome and reiterate the importance of understanding and standardizing the methodology and algorithms behind commercial neuromonitoring devices prior to incorporating them in clinical use.

Time Thresholds for Using Pressure Reactivity Index in Neuroprognostication for Patients With Severe Traumatic Brain Injury.

Severe traumatic brain injury (sTBI) represents a diffuse, heterogeneous disease where therapeutic targets for optimizing clinical outcome remain unclear. Mean pressure reactivity index (PRx) values have demonstrated associations with clinical outcome in sTBI. However, the retrospective derivation of a mean value diminishes its bedside significance. We evaluated PRx temporal profiles for patients with sTBI and identified time thresholds suggesting optimal neuroprognostication. Patients with sTBI and continuous bolt intracranial pressure monitoring were identified. Outcomes were dichotomized by disposition status ("good outcome" was denoted by home and acute rehabilitation). PRx values were obtained every minute by taking moving correlation coefficients of intracranial pressures and mean arterial pressures. Average PRx trajectories for good and poor outcome groups were calculated by extending the last daily averaged PRx value to day 18. Each patient also had smoothed PRx trajectories that were used to generate "candidate features." These "candidate features" included daily average PRx's, cumulative first-order changes in PRx and cumulative second-order changes in PRx. Changes in sensitivity over time for predicting poor outcome was then evaluated by generating penalized logistic regression models that were derived from the "candidate features" and maximized specificity. Among 33 patients with sTBI, 18 patients achieved good outcome and 15 patients had poor outcome. Average PRx trajectories for the good and poor outcome groups started on day 6 and consistently diverged at day 9. When targeting a specificity >83.3%, an 85% maximum sensitivity for determining poor outcome was achieved at hospital day 6. Subsequent days of PRx monitoring showed diminishing sensitivities. Our findings suggest that in a population of sTBI, PRx sensitivities for predicting poor outcome was maximized at hospital day 6. Additional study is warranted to validate this model in larger populations.

Autoregulatory Management in Traumatic Brain Injury: The Role of Absolute Pressure Reactivity Index Values and Optimal Cerebral Perfusion Pressure Curve Shape.

The aim of this study was to investigate if the absolute pressure reactivity index (PRx) value influenced the association between cerebral perfusion pressure (CPP) and outcome and if the optimal CPP (CPPopt) curve shape influenced the association between deviation from CPPopt and outcome in traumatic brain injury (TBI). We included 383 TBI patients treated at the neurointensive care in Uppsala between 2008 and 2018 with at least 24 h of CPP data. To determine the influence of absolute PRx values on the association between absolute CPP and outcome, the percentage of monitoring time for combinations of CPP and PRx were correlated with outcome (Extended Glasgow Outcome Scale [GOS-E]) in a heatmap. To determine the association between CPP and the relatively best PRx (CPPopt), the percentage of monitoring time of ΔCPPopt (actual CPP-CPPopt) ±5 mm Hg was analyzed in relation to GOS-E. To determine the association between CPP and the relatively best PRx within a certain absolute PRx range (curve shape), both the percentage of ΔCPPopt within the absolute limits of reactivity (PRx <0.00, < 0.15, etc.) and within certain confidence intervals of PRx-deterioration (+0.025, +0.05 etc.) from CPPopt were analyzed in relation to GOS-E. The heatmap of PRx and absolute CPP versus outcome indicated that the CPP range (55-75 mm Hg) associated with favorable outcome was wider when PRx was below 0, whereas the upper CPP-threshold decreased as PRx increased. CPPopt could be calculated during 53% of the monitoring time. Higher percentage of monitoring time with ΔCPPopt ±5 mm Hg, ΔCPPopt within the reactivity-thresholds (PRx <0.30), and ΔCPPopt within the PRx-confidence interval +0.025 were all independently associated with favorable outcome in separate logistic regressions. These regressions had similar area under receiver operating curve and were not superior to a similar regression when the CPPopt-target was replaced by the percentage of monitoring time within the traditional fixed CPP-targets 60 to 70 mm Hg. Individualized CPPopt-targets exhibited a comparable outcome association as traditional CPP targets and different definitions of the best CPPopt range based on the PRx value had a limited effect on the association between deviation from CPPopt and outcome. Since CPPopt could only be calculated during half of the time, an alternative approach would be to assess the absolute PRx to anticipate a safe CPP range.

Effects of short-term hyperoxemia on cerebral autoregulation and tissue oxygenation in acute brain injured patients.

Introduction: Potential detrimental effects of hyperoxemia on outcomes have been reported in critically ill patients. Little evidence exists on the effects of hyperoxygenation and hyperoxemia on cerebral physiology. The primary aim of this study is to assess the effect of hyperoxygenation and hyperoxemia on cerebral autoregulation in acute brain injured patients. We further evaluated potential links between hyperoxemia, cerebral oxygenation and intracranial pressure (ICP). Methods: This is a single center, observational, prospective study. Acute brain injured patients [traumatic brain injury (TBI), subarachnoid hemorrhage (SAH), intracranial hemorrhage (ICH)] undergoing multimodal brain monitoring through a software platform (ICM+) were included. Multimodal monitoring consisted of invasive ICP, arterial blood pressure (ABP) and near infrared spectrometry (NIRS). Derived parameters of ICP and ABP monitoring included the pressure reactivity index (PRx) to assess cerebral autoregulation. ICP, PRx, and NIRS-derived parameters (cerebral regional saturation of oxygen, changes in concentration of regional oxy- and deoxy-hemoglobin), were evaluated at baseline and after 10min of hyperoxygenation with a fraction of inspired oxygen (FiO2) of 100% using repeated measures t-test or paired Wilcoxon signed-rank test. Continuous variables are reported as median (interquartile range). Results: Twenty-five patients were included. The median age was 64.7years (45.9-73.2), and 60% were male. Thirteen patients (52%) were admitted for TBI, 7 (28%) for SAH, and 5 (20%) patients for ICH. The median value of systemic oxygenation (partial pressure of oxygen-PaO2) significantly increased after FiO2 test, from 97 (90-101) mm Hg to 197 (189-202) mm Hg, p < 0.0001. After FiO2 test, no changes were observed in PRx values (from 0.21 (0.10-0.43) to 0.22 (0.15-0.36), p = 0.68), nor in ICP values (from 13.42 (9.12-17.34) mm Hg to 13.34 (8.85-17.56) mm Hg, p = 0.90). All NIRS-derived parameters reacted positively to hyperoxygenation as expected. Changes in systemic oxygenation and the arterial component of cerebral oxygenation were significantly correlated (respectively ΔPaO2 and ΔO2Hbi; r = 0.49 (95% CI = 0.17-0.80). Conclusion: Short-term hyperoxygenation does not seem to critically affect cerebral autoregulation.

Early Electroencephalographic Features Predicting Cerebral Physiology and Functional Outcomes After Pediatric Traumatic Brain Injury.

We investigated whether early electroencephalographic features predicted intracranial pressure (ICP), cerebrovascular pressure reactivity, brain tissue oxygenation, and functional outcomes in patients with pediatric traumatic brain injury (TBI). This was a retrospective analysis of a prospective data set of 63 patients with pediatric TBI. Electroencephalographic features were collected in the first 24h of recording to predict values of ICP, pressure reactivity index (PRx), and brain tissue oxygenation (PbtO2) through the initial 7days of critical care monitoring, in addition to Glasgow Outcome Scale Extended-Pediatric Revision (GOSE-Peds) scores at 12months. Electroencephalographic features were averaged over all surface electrodes and included seizures, interictal epileptiform discharges, suppression percentage, complexity, the alpha/delta power ratio, and both absolute asymmetry indices and power in beta (13-20Hz), alpha (8-13Hz), theta (4-7Hz) and delta (0-4Hz) bands. Demographic data and injury severity scores, such as the Glasgow Coma Scale (GCS) and Pediatric Risk of Mortality III (PRISM III) scores, at presentation were also assessed. Univariate and multiple linear regression with guided stepwise variable selection was used to find combinations of risk factors that best explain variability in ICP, PRx, PbtO2, and GOSE-Peds values, and best fit models were applied to pediatric age strata. We hypothesized that suppression percentage and the alpha/delta power ratio in the first 24h of recording predict ICP, PRx, PbtO2, and GOSE-Peds values. Best subset model selection identified that increased suppression percentage and PRISM III scores predicted increased ICP (R2 = 79%, Akaike information criterion [AIC] = 332.30, root mean square error [RMSE] = 6.62), with suppression percentages < 5% (slope = - 5687.0, p = 0.0001) and ≥ 45% (slope = 9825.9, p = 0.0000) being predictive of dose of intracranial hypertension. When accounting for age and GCS score, increased suppression percentage predicted increased PRx values, suggestive of inefficient cerebrovascular pressure reactivity (R2 = 53%, AIC = 3.93, RMSE = 0.23), with suppression percentages ≥ 5% (p = 0.0033) and ≥ 45% (p = 0.0027) being predictive of median PRx values ≥ 0.3. Lower GCS scores, the presence of seizures, and increased suppression percentages each were independently associated with higher GOSE-Peds scores (R2 = 52%, AIC = 194.04, RMSE = 1.58), suggestive of unfavorable outcomes, with suppression percentages ≥ 5% (p = 0.0005) and ≥ 45% (p = 0.0000) being predictive of GOSE-Peds scores ≥ 5. At the univariate level, no electroencephalographic or clinical feature was associated with differences in PbtO2 values. Increased electroencephalographic suppression percentage on the initial day of monitoring may identify patients with pediatric TBI at risk of increased ICP, inefficient cerebrovascular pressure reactivity, and unfavorable outcomes.

Intracranial Pressure-Derived Cerebrovascular Reactivity Indices, Chronological Age, and Biological Sex in Traumatic Brain Injury: A Scoping Review.

To date, there has been limited literature exploring the association between age and sex with cerebrovascular reactivity (CVR) in moderate/severe traumatic brain injury (TBI). Given the known link between age, sex, and cerebrovascular function, knowledge of the impacts on continuously assessed CVR is critical for the development of future therapeutics. We conducted a scoping review of the literature for studies that had a direct statistical interrogation of the relationship between age, sex, and continuous intracranial pressure (ICP)-based indices of CVR in moderate/severe TBI. The ICP-based indices researched included: pressure reactivity index (PRx), pulse amplitude index (PAx), and RAC. MEDLINE, BIOSIS, EMBASE, SCOPUS, Global Health, and the Cochrane library were searched from inception to June 2021 for relevant articles. A total of 10 original studies fulfilled our inclusion criteria. Nine of the articles documented a correlation between advanced age and worse CVR, with eight using PRx (2192 total patients), three using PAx (978 total patients), and one using RAC (358 total patients), p < 0.05; R ranging from 0.17 to 0.495 for all indices across all studies. Three articles (1256 total patients) displayed a correlation between biological sex and PRx, with females trending towards higher PRx values (p < 0.05) in the limited available literature. However, no literature exists comparing PAx or RAC with biological sex. Findings showed that aging was associated with impaired CVR. We observed a trend between female sex and worse PRx values, but the literature was limited and statistical significance was borderline. The identified studies were few in number, carried significant population heterogeneity, and utilized grand averaging of large epochs of physiology during statistical comparisons with age and biological sex. Because of the heterogeneous nature of TBI populations and limited focus on the effects of age and sex on outcomes in TBI, it is challenging to highlight the differences between the indices and patient age groups and sex. The largest study showing an association between PRx and age was done by Zeiler and colleagues, where 165 patients were studied noting that patients with a mean PRx value above zero had a mean age above 51.4 years versus a mean age of 41.4 years for those with a mean PRx value below zero (p = 0.0007). The largest study showing an association between PRx and sex was done by Czosnyka and colleagues, where 469 patients were studied noting that for patients <50 years of age, PRx was worse in females (0.11 ± 0.047) compared to males (0.044 ± 0.031), p < 0.05. The findings from these 10 studies provide preliminary data, but are insufficient to definitively characterize the impact of age and sex on CVR in moderate/severe TBI. Future work in the field should focus on the impact of age and sex on multi-modal cerebral physiological monitoring.

Relationship of Pressure Reactivity Index and Delayed Cerebral Ischemia in Aneurysmal Subarachnoid Hemorrhage.

Patients with aneurysmal subarachnoid hemorrhage (SAH) continue to have poor functional outcome due to the occurrence of delayed cerebral ischemia (DCI). Although vasospasm represents the primary therapeutic target for mitigating DCI, DCI occurs through multifocal etiologies that involve impaired cerebral autoregulation. Worse pressure reactivity index (PRx) values, which consists of a moving correlation coefficient between intracranial pressures and mean arterial pressures, have been shown to be associated with DCI in non-randomized clinical trials. We discuss two patients that presented with high-grade SAH and comatose exams. Patient one was a 34-year-old male diagnosed with SAH from a ruptured right middle cerebral artery aneurysm. He had intact PRx values (Mean: -0.07 during hospital days 9-19), while having severe, refractory vasospasm. At the conclusion of his hospitalization, he was functionally independent, had negligible DCI, and was successfully discharged home. Patient two was a 78-year-old female diagnosed with SAH from a ruptured anterior communicating artery aneurysm. She had an improving PRx ranging from -0.1 to 0.1 early in her hospitalization. However, upon developing severe vasospasm, her PRx increased to 0.6 (overall PRx from hospital days 4-16 was 0.3), and she suffered from extensive DCI in bilateral middle cerebral and anterior cerebral artery distributions that ultimately resulted in malignant cerebral edema and brain death. Cerebral autoregulation as measured by PRx may represent a viable target for neuroprognostication by evaluating DCI risk in patients with SAH who develop severe or refractory vasospasm. Further studies evaluating the role of cerebral autoregulation, PRx, and its pathophysiological role in DCI are warranted.

Association of Outcomes with Model-Based Indices of Cerebral Autoregulation After Pediatric Traumatic Brain Injury.

We investigated whether model-based indices of cerebral autoregulation (CA) are associated with outcomes after pediatric traumatic brain injury. This was a retrospective analysis of a prospective clinical database of 56 pediatric patients with traumatic brain injury undergoing intracranial pressure monitoring. CA indices were calculated, including pressure reactivity index (PRx), wavelet pressure reactivity index (wPRx), pulse amplitude index (PAx), and correlation coefficient between intracranial pressure pulse amplitude and cerebral perfusion pressure (RAC). Each CA index was used to compute optimal cerebral perfusion pressure (CPP). Time of CPP below lower limit of autoregulation (LLA) or above upper limit of autoregulation (ULA) were computed for each index. Demographic, physiologic, and neuroimaging data were collected. Primary outcome was determined using Pediatric Glasgow Outcome Scale Extended (GOSE-Peds) at 12months, with higher scores being suggestive of unfavorable outcome. Univariate and multiple linear regression with guided stepwise variable selection was used to find combinations of risk factors that can best explain the variability of GOSE-Peds scores, and the best fit model was applied to the age strata. We hypothesized that higher GOSE-Peds scores were associated with higher CA values and more time below LLA or above ULA for each index. At the univariate level, CPP, dose of intracranial hypertension, PRx, PAx, wPRx, RAC, percent time more than ULA derived for PAx, and percent time less than LLA derived for PRx, PAx, wPRx, and RAC were all associated with GOSE-Peds scores. The best subset model selection on all pediatric patients identified that when accounting for CPP, increased dose of intracranial hypertension and percent time less than LLA derived for wPRx were independently associated with higher GOSE-Peds scores. Age stratification of the best fit model identified that in children less than 2years of age or 8years of ageor more, percent time less than LLA derived for wPRx represented the sole independent predictor of higher GOSE-Peds scores when accounting for CPP and dose of intracranial hypertension. For children 2years or younger to less than 8years of age, dose of intracranial hypertension was identified as the sole independent predictor of higher GOSE-Peds scores when accounting for CPP and percent time less than LLA derived for wPRx. Increased dose of intracranial hypertension, PRx, wPRx, PAx, and RAC values and increased percentage time less than LLA based on PRx, wPRx, PAx, and RAC are associated with higher GOSE-Peds scores, suggestive of unfavorable outcome. Reducing intracranial hypertension and maintaining CPP more than LLA based on wPRx may improve outcomes and warrants prospective investigation.

Monitoring cerebrovascular reactivity in pediatric traumatic brain injury: comparison of three methods.

To study three different methods of monitoring cerebral autoregulation in children with severe traumatic brain injury. Prospective cohort study of all children admitted to the pediatric intensive care unit at a university-affiliated hospital with severe TBI over a 4-year period to study three different methods of monitoring cerebral autoregulation: pressure-reactivity index (PRx), transcranial Doppler derived mean flow velocity index (Mx), and near-infrared spectroscopy derived cerebral oximetry index (COx). Twelve patients were included in the study, aged 5months to 17years old. An empirical regression analyzing dependence of PRx on cerebral perfusion pressure (CPP) displayed the classic U-shaped distribution, with low PRx values (< 0.3) reflecting intact auto-regulation, within the CPP range of 50-100mmHg. The optimal CPP was 75-80mmHg for PRx and COx. The correlation coefficients between the three indices were as follows: PRx vs Mx, r = 0.56; p < 0.0001; PRx vs COx, r = 0.16; p < 0.0001; and COx vs Mx, r = 0.15; p = 0.022. The mean PRx with a cutoff value of 0.3 predicted correctly long-term outcome (p = 0.015). PRx seems to be the most robust index to access cerebrovascular reactivity in children with TBI and has promising prognostic value. Optimal CPP calculation is feasible with PRx and COx.

Systemic Markers of Injury and Injury Response Are Not Associated with Impaired Cerebrovascular Reactivity in Adult Traumatic Brain Injury: A Collaborative European Neurotrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) Study

The role of extra-cranial injury burden and systemic injury response on cerebrovascular response in traumatic brain injury (TBI) is poorly documented. This study preliminarily assesses the association between admission features of extra-cranial injury burden on cerebrovascular reactivity. Using the Collaborative European Neurotrauma Effectiveness Research in TBI High-Resolution ICU (HR ICU) sub-study cohort, we evaluated those patients with both archived high-frequency digital intra-parenchymal intra-cranial pressure monitoring data of a minimum of 6 h in duration, and the presence of a digital copy of their admission computed tomography (CT) scan. Digital physiologic signals were processed for pressure reactivity index (PRx) and both the percent time above defined PRx thresholds and mean hourly dose above threshold. This was conducted for both the first 72 h and entire duration of recording. Admission extra-cranial injury characteristics and CT injury scores were obtained from the database, with quantitative contusion, edema, intraventricular hemorrhage, and extra-axial lesion volumes were obtained via semi-automated segmentation. Comparison between admission extra-cranial markers of injury and PRx metrics was conducted using Mann-Whitney U testing, and logistic regression techniques, adjusting for known CT injury metrics associated with impaired PRx. A total of 165 patients were included. Evaluating the entire ICU recording period, there was limited association between metrics of extra-cranial injury burden and impaired cerebrovascular reactivity. Using the first 72 h of recording, admission temperature (p = 0.042) and white blood cell % (WBC %; p = 0.013) were statistically associated with impaired cerebrovascular reactivity on Mann-Whitney U and univariate logistic regression. After adjustment for admission age, pupillary status, GCS motor score, pre-hospital hypoxia/hypotension, and intra-cranial CT characteristics associated with impaired reactivity, temperature (p = 0.021) and WBC % (p = 0.013) remained significantly associated with mean PRx values above +0.25 and +0.35, respectively. Markers of extra-cranial injury burden and systemic injury response do not appear to be strongly associated with impaired cerebrovascular reactivity in TBI during both the initial and entire ICU stay.

Significance of ICP-related parameters for the treatment and outcome of severe traumatic brain injury.

ObjectiveTo analyze the significance of intracranial pressure (ICP)-related parameters on outcome in patients with severe traumatic brain injury. The ICP-related parameters included ICP, ICP dose (DICP), regression of the correlation coefficient between amplitude and pressure (RAP), pressure reactivity index (PRx), and cerebral perfusion pressure (CPP).MethodsA retrospective analysis was performed using clinical information from 29 patients with severe traumatic brain injury who were admitted to the Department of Neurosurgery from January 2018 to January 2019. All patients underwent ICP probe implantation after admission. Patients were followed up for 6 months after discharge, and were categorized into either the favorable or unfavorable outcome group based on their Glasgow Outcome Scale score. The differences in ICP, DICP, RAP, PRx, and CPP between the two groups were analyzed for their effects on outcome.ResultsThe average ICP, DICP, PRx, and RAP values in patients with favorable outcomes were significantly lower than in patients with unfavorable outcomes, while CPP values were significantly higher in the favorable outcome group.ConclusionAverage ICP, DICP, PRx, RAP, and CPP values may indicate disease status and relate to patient outcomes. It is important to use multiple parameters to predict patients’ disease severity and prognosis.

Lack of agreement between optimal mean arterial pressure determination using pressure reactivity index versus cerebral oximetry index in hypoxic ischemic brain injury after cardiac arrest

IntroductionInvasive monitoring of cerebral autoregulation using the pressure reactivity index (PRx) allows for the determination of optimal mean arterial pressure (MAPOPT) in hypoxic ischemic brain injury (HIBI) patients following cardiac arrest. However, the utility of non-invasive surrogates to determine MAPOPT has not been addressed. We aimed to determine the agreement between PRx-derived MAPOPT versus MAPOPT determined by the near-infrared spectroscopy (NIRS) based cerebral oximetry index (COx). MethodsTen HIBI patients were enrolled. PRx-derived MAPOPT, lower (LLA) and upper limits of autoregulation (ULA) were compared against COx-derived MAPOPT, LLA and ULA. Multimodal neuromonitoring included mean arterial pressure, intracranial pressure, brain tissue oxygenation, jugular venous oxygen saturation, and NIRS-derived regional cerebral oxygen saturation. ResultsRepeated measures Bland–Altman plots demonstrated limited agreement between MAPOPT derived from COx and PRx (mean bias: 1.4 mmHg; upper limit of agreement: 25.9 mmHg; lower limit of agreement: −23.0 mmHg). Similarly, there was limited agreement between the absolute values of PRx and COx. Mean bias was 0.26 and the upper and lower limits of agreement were 1.05 and −0.53, respectively. Systematic bias was apparent, whereby at low PRx values COx overestimated PRx and at high PRx values, COx underestimated PRx. COx was limited in its ability to determine impaired autoregulation defined by PRx (receiver operator characteristic area under the curve was 0.488). ConclusionCollectively, we demonstrate that COx-based determination of MAPOPT lacks agreement with MAPOPT derived from PRx. Further research must be done to evaluate the physiologic and clinical efficacy of PRx derived MAPOPT in HIBI.

Abstract 410: Early Imaging Incompletely Predicts Subsequent Cerebral Physiological Derangements After Cardiac Arrest

Introduction: Decreased grey-white matter ratio (GWR) on early head CT scans correlates with poor outcome after cardiac arrest. However, it is unknown if early imaging features fully predict of subsequent derangments in cerebral physiology that cause secondary brain injury. Hypothesis: GWR on early head CT correlates with average intracranial pressure (ICP), brain tissue oxygen (PbtO2), and pressure reactivity (a proxy for cerebral autoregulation) after cardiac arrest. Methods: A total of 30 post-arrest patients were identified over a 3-year period who underwent head CT within 1 day of arrest as well as intracranial monitoring (IM) during hospitalization. 5 patients were excluded either due to unavailable IM recordings (n=1) or motion degraded head CTs (n=4). ICP, P bt O 2 , and mean arterial pressure (MAP) were recorded continuously using a bedside recording unit (CNS Monitor, Moberg Research Inc). Pressure reactivity index (PRx), was calculated as the Pearson correlation coefficient between ICP and MAP over 5 minute intervals, updated every minute. GWR was measured for the basal ganglia from Hounsfield unit measurements made from initial head CT. Relationships between average ICP, PRx, P bt O 2 and GWR was calculated using linear regression. Results: Average GWR for the cohort was 1.2154. Average ICP was weakly correlated with initial GWR (R 2 =0.257, p=0.01). A trend towards higher PRx values was seen with lower initial GWR; however, this did not reach statistical significance (R 2 =0.15, p=0.07). There was no relation between average P bt O 2 and GWR (R 2 =0.02, p=0.56). Conclusions: Lower initial GWR is associated with higher average ICP, and may also be associated with disorderd cerebral autoregulation. However, no relationship could be identified between initial imaging findings and average brain oxygen levels. These data imply that physiological stressors such as brain hypoxia are not predicted by initial imaging findings and suggests a role for invasive neuromonitoring to identify and treat processes that promote secondary brain injury.

Abstract 12: Cerebrovascular Pressure Reactivity Predicts Outcome in Diffuse Hypoxic-Ischemic Brain Injury

Introduction: Outcome prediction after diffuse hypoxic-ischemic brain injury (HIBI), which most commonly occurs after sudden cardiac arrest, remains fraught with uncertainty. Cerebral autoregulation (CA) normally limits fluctuations in cerebral blood flow through pressure induced changes in cerebral arteriolar diameter. CA is disrupted after brain injury, and the degree of autoregulatory failure correlates with the severity of brain injury. CA measurements may thus enable more accurate outcome prediction after HIBI. Hypothesis: We hypothesized that the degree of impairment in cerebrovascular pressure reactivity, one of the principle mechanisms of CA, correlates with the extent of HIBI and can predict outcome. Methods: Intracranial pressure (ICP) and mean arterial pressure (MAP) were continuously recorded for all subjects. The Pressure Reactivity Index (PRx) was calculated as a moving linear correlation coefficient between ICP and MAP for each 30 sec data epoch. PRx is positive when ICP increases in concert with MAP and implies impaired pressure reactivity. For each subject, both the mean PRx for the entire recording session as well as the proportion of PRx values &gt; 0.2 (previously found to predict poor outcome in TBI) were calculated. Results: We included 22 consecutive patients with HIBI who underwent invasive ICP monitoring in this single center observational study between 02/2016-02/2018. Median age was 41 (range 20-77), 36% (8/22) survived to hospital discharge, and 18% (4/22) had return of consciousness. The median time of ICP monitoring was 101 hr (range 8-381 hr). HIBI was due to cardiac arrest in 19/22 patients and prolonged hypoxia in 3/22. Mean PRx was significantly higher in patients without return of consciousness (0.49 ± 0.05 vs. 0.036 ± 0.032, p = 0.001), as was the proportion of PRx values &gt; 0.2 (0.73 ± 0.037 vs 0.34 ± 0.058, p &lt; 0.001). All patients with return of consciousness had mean PRx &lt; 0.2. Using this cutoff value, PRx had a 94% sensitivity and 100% specificity for predicting death or vegetative state. Conclusions: Continuous pressure reactivity measurements correlate with outcome after HIBI, and may be a useful adjunct for neuroprognostication. Future studies are needed to validate these findings in larger cohorts.

Deriving the PRx and CPPopt from 0.2-Hz Data: Establishing Generalizability to Bedmaster Users.

The objective was to explore the validity of industry-parameterized vital signs in the generation of pressure reactivity index (PRx) and optimal cerebral perfusion pressure (CPPopt) values. Ten patients with intracranial pressure (ICP) monitors from 2008 to 2013 in a tertiary care hospital were included. Arterial blood pressure (ABP) and ICP were sampled at 240 Hz (of waveform data) and 0.2 Hz (of parameterized data produced by heuristic industry proprietary algorithms). 240-Hz ABP were filtered for pulse pressure and diastolic ABP within the limits of 20-150 mmHg. The PRx was calculated as Pearson's correlation coefficient using 10-s averages of ICP and ABP over a 5-min moving window with 80% overlap. For ease of comparison, we used the naming convention of BMx for PRx values derived from 0.2-Hz data. A 5-min median cerebral perfusion pressure (CPP) trend was calculated, PRx or BMx values divided and averaged into CPP bins spanning 5 mmHg. The minimum Y value (PRx or BMx) of the parabolic function fit to the resulting XY plot of 4 h of data was obtained, and updated every 1 min. Pearson's R correlations were calculated for each patient. Linear mixed-effects models were used with a random intercept to assess the overall correlation between the PRx (outcome) and the BMx (fixed effect) or the CPPopt-PRx (outcome) and the CPPopt-BMx (fixed effect). The overall correlation between the PRx and BMx was 0.78 based on the linear mixed effects models (p < 0.0001), and the overall correlation for the CPPopt-PRx and CPPopt-BMx based on the linear mixed effects models was 0.76 (p < 0.0001). One patient had low correlation of CPPopts derived from the PRx vs the BMx; this patient had the least number of hours of CPPopt data to compare. The BMx shows promise in CPPopt derivation against the validated PRx measure. If further developed, it could expand the capability of centers to derive CPPopt goals for use in clinical trials.

Detection of Impaired Cerebral Autoregulation Using Selected Correlation Analysis: A Validation Study.

Multimodal brain monitoring has been utilized to optimize treatment of patients with critical neurological diseases. However, the amount of data requires an integrative tool set to unmask pathological events in a timely fashion. Recently we have introduced a mathematical model allowing the simulation of pathophysiological conditions such as reduced intracranial compliance and impaired autoregulation. Utilizing a mathematical tool set called selected correlation analysis (sca), correlation patterns, which indicate impaired autoregulation, can be detected in patient data sets (scp). In this study we compared the results of the sca with the pressure reactivity index (PRx), an established marker for impaired autoregulation. Mean PRx values were significantly higher in time segments identified as scp compared to segments showing no selected correlations (nsc). The sca based approach predicted cerebral autoregulation failure with a sensitivity of 78.8% and a specificity of 62.6%. Autoregulation failure, as detected by the results of both analysis methods, was significantly correlated with poor outcome. Sca of brain monitoring data detects impaired autoregulation with high sensitivity and sufficient specificity. Since the sca approach allows the simultaneous detection of both major pathological conditions, disturbed autoregulation and reduced compliance, it may become a useful analysis tool for brain multimodal monitoring data.

Bedside Xenon-CT Shows Lower CBF in SAH Patients with Impaired CBF Pressure Autoregulation as Defined by Pressure Reactivity Index (PRx).

Subarachnoid hemorrhage (SAH) is a disease with a high rate of unfavorable outcome, often related to delayed cerebral ischemia (DCI), i.e., ischemic injury that develops days-weeks after onset, with a multifactorial etiology. Disturbances in cerebral pressure autoregulation, the ability to maintain a steady cerebral blood flow (CBF), despite fluctuations in systemic blood pressure, have been suggested to play a role in the development of DCI. Pressure reactivity index (PRx) is a well-established measure of cerebral pressure autoregulation that has been used to study traumatic brain injury, but not extensively in SAH. To study the relation between PRx and CBF in SAH patients, and to examine if PRx can be used to predict DCI. Retrospective analysis of prospectively collected data. PRx was calculated as the correlation coefficient between mean arterial blood pressure (MABP) and intracranial pressure (ICP) in a 5min moving window. CBF was measured using bedside Xenon-CT (Xe-CT). DCI was diagnosed clinically. 47 poor-grade mechanically ventilated patients were studied. Patients with disturbed pressure autoregulation (high PRx values) had lower CBF, as measured by bedside Xe-CT; both in the early (day 0-3) and late (day 4-14) acute phase of the disease. PRx did not differ significantly between patients who developed DCI or not. In mechanically ventilated and sedated SAH patients, high PRx (more disturbed CBF pressure autoregulation) is associated with low CBF, both day 0-3 and day 4-14 after onset. The role of PRx as a monitoring tool in SAH patients needs further studying.

Optimal cerebral perfusion pressure in patients with intracerebral hemorrhage: an observational case series

IntroductionCurrent guidelines for spontaneous intracerebral hemorrhage (ICH) recommend maintaining cerebral perfusion pressure (CPP) between 50 and 70 mmHg, depending on the state of autoregulation. We continuously assessed dynamic cerebral autoregulation and the possibility of determination of an optimal CPP (CPPopt) in ICH patients. Associations between autoregulation, CPPopt and functional outcome were explored.MethodsIntracranial pressure (ICP), mean arterial pressure (MAP) and CPP were continuously recorded in 55 patients, with 38 patients included in the analysis. The pressure reactivity index (PRx) was calculated as moving correlation between MAP and ICP. CPPopt was defined as the CPP associated with the lowest PRx values. CPPopt was calculated using hourly updated of 4 hour windows. The modified Rankin Scale (mRS) was assessed at 3 months and associations between PRx, CPPopt and outcomes were explored using Pearson correlation and Fisher’s exact test. Multivariate stepwise logistic regression models were calculated including standard outcome predictors along with percentage of time with PRx >0.2 and percentage of time within the CPPopt range.ResultsAn overall PRx indicating impairment of pressure reactivity was found in 47% of patients (n = 18). The mean PRx and the time spent with a PRx > 0.2 significantly correlated with mRS at 3 months (r = 0.50, P = 0.002; r = 0.46, P = 0.004). CPPopt was calculable during 57% of the monitoring time. The median CPP was 78 mmHg, the median CPPopt 83 mmHg. Mortality was lowest in the group of patients with a CPP close to their CPPopt. However, for none of the CPPopt variables a significant association to outcome was found. The percentage of time with impaired autoregulation and hemorrhage volume were independent predictors for acceptable outcome (mRS 1 to 4) at three months.ConclusionsFailure of pressure reactivity seems common following severe ICH and is associated with unfavorable outcome. Real-time assessment of CPPopt is feasible in ICH and might provide a tool for an autoregulation-oriented CPP management. A larger trial is needed to explore if a CPPopt management results in better functional outcomes.