Cerebral autoregulation in traumatic brain injury: ultra-low-frequency pressure reactivity index and intracranial pressure across age groups

Abstract

Background: The ultra-low-frequency pressure reactivity index (UL-PRx) has been established as a surrogate method for bedside estimation of cerebral autoregulation (CA). Although this index has been shown to be a predictor of outcome in adult and pediatric patients with traumatic brain injury (TBI), a comprehensive evaluation of low sampling rate data collection (0.0033 Hz averaged over 5 min) on cerebrovascular reactivity has never been performed.

Objective: To evaluate the performance and predictive power of the UL-PRx for 12-month outcome measures, alongside all International Mission for Prognosis and Analysis of Clinical Trials (IMPACT) models and in different age groups. To investigate the potential for optimal cerebral perfusion pressure (CPPopt).

Methods: Demographic data, IMPACT variables, in-hospital mortality, and Glasgow Outcome Scale Extended (GOSE) at 12 months were extracted. Filtering and processing of the time series and creation of the indices (cerebral intracranial pressure (ICP), cerebral perfusion pressure (CPP), UL-PRx, and deltaCPPopt (ΔCPPopt and CPPopt-CPP)) were performed using an in-house algorithm. Physiological parameters were assessed as follows: mean index value, % time above threshold, and mean hourly dose above threshold.

Results: A total of 263 TBI patients were included: pediatric (17.5% aged ≤ 16 y) and adult (60.5% aged > 16 and < 70 y and 22.0% ≥ 70 y, respectively) patients. In-hospital and 12-month mortality were 25.9% and 32.7%, respectively, and 60.0% of patients had an unfavorable outcome at 12 months (GOSE). On univariate analysis, ICP, CPP, UL-PRx, and ΔCPPopt were associated with 12-month outcomes. The cutoff of ~ 20-22 for mean ICP and of ~ 0.30 for mean UL-PRx were confirmed in all age groups, except in patients older than 70 years. Mean UL-PRx remained significantly associated with 12-month outcomes even after adjustment for IMPACT models. This association was confirmed in all age groups. UL-PRx resulted associate with CPPopt.

Conclusions: The study highlights UL-PRx as a tool for assessing CA and valuable outcome predictor for TBI patients. The results emphasize the potential clinical utility of the UL-PRx and its adaptability across different age groups, even after adjustment for IMPACT models. Furthermore, the correlation between UL-PRx and CPPopt suggests the potential for more targeted treatment strategies.

Trial registration: ClinicalTrials.gov identifier: NCT05043545, principal investigator Paolo Gritti, date of registration 2021.08.21.

Keywords: Age group; Cerebral autoregulation; Cerebrovascular reactivity; Intracranial pressure; Optimal cerebral perfusion pressure; Pressure reactivity index; Traumatic brain injury; Ultra-low-frequency pressure reactivity index.

Fig. 1

Flowchart of the study cohort. TBI Traumatic Brain Injury; ICP Intracranial Pressure; and PICU Pediatric Intensive Care Unit

Fig. 2

Receiver operating characteristic (ROC) curve of the predictive model of mortality (A) and unfavorable outcome (B). The figure displays ROC curves for four logistic regression models predicting mortality (A) and unfavorable outcome (B). Each model incorporates the different sets of predictor variables of the IMPACT models (core, core + CT, core + CT + lab). The last model further includes the mean UL-PRx. The legend indicates the corresponding AUC values for each model. The IMPACT core + CT + lab + UL-PRx model demonstrated significantly superior performance for predicting both mortality and unfavorable outcomes

Fig. 3

A–D Relationship between CPP and UL-PRx, stratified by age and GOSE. The combined plot illustrates a comparative analysis of ultra-low-pressure reactivity index (UL-PRx) dynamics in patients with traumatic brain injury, specifically examining the relationship between cerebral perfusion pressure (CPP) and UL-PRx. The plot is divided into four quadrants, each focusing on different patient groups based on Glasgow Outcome Scale Extended (GOSE) scores and age categories. The upper left quadrant examines autoregulation patterns for GOSE 1–4 patients aged 16 years or younger, while the upper right quadrant examines patients older than 16 years. The lower left quadrant provides insights into UL-PRx dynamics for GOSE 5–8 patients aged 16 years or younger, while the lower right quadrant examines the same for those aged 16 years or older. Each bar represents the mean UL-PRx value for specific CPP groups, with error bars indicating 95% confidence intervals. In the top panels, patients with poorer GOSE scores show a trend toward higher UL-PRx values, both in the pediatric and adult populations. Conversely, the lower panels, representing patients with higher CPP and positive results, show a trend toward values close to or predominantly negative UL-PRx

Fig. 4

A–D Visual examination of UL-PRx dynamics and CPP stratified by age and GOSE. The results, visually represented in the figure by smoothing curves and confidence intervals, clearly show a gradual escalation of high UL-PRx values indicating impaired cerebral autoregulation (CA), especially at low CPP values (CPP below the threshold of about 50 mmHg). Of note, individuals with unfavorable outcomes tend to have lower CPP values and thus show a more pronounced increase in UL-PRx. The figure provides valuable insight into the relationship between CPP and UL-PRx in different age groups and categories of the Glasgow Outcome Scale and sheds light on the potential impact on cerebral autoregulation in patients with traumatic brain injury