Visualizing and Interpreting the Carbon Dioxide Reactivity Index in Traumatic Brain Injury

Cerebral autoregulation is routinely assessed through variations in intracranial pressure (ICP) and systemic hemodynamic parameters; however, its metabolic dimension remains underexplored in clinical settings. This study introduces the carbon dioxide reactivity index (CO₂Rx), a novel metric derived from continuous ICP and end-tidal CO₂ (ETCO₂) monitoring aimed at capturing real-time cerebrovascular metabolic reactivity in patients with severe traumatic brain injury (TBI).

We performed a retrospective observational analysis of patients with moderate and severe TBI admitted to a single adult and pediatric trauma center. CO₂Rx was calculated as a moving Pearson correlation between ICP and ETCO₂ across 60-min windows using low-frequency time-series data. Heatmaps and contour plots visualized median CO₂Rx values across ICP and ETCO₂ ranges. Analyses were stratified by age, decompressive craniectomy status, and 12-month outcomes. A graphical framework linked CO₂Rx/ICP/ETCO₂ combinations to outcome probabilities.

A total of 218 patients (178 adults, 40 pediatric patients) were included. Higher CO₂Rx values, indicative of preserved metabolic reactivity, were observed when ICP was ≤ 20 mm Hg, and ETCO₂ ranged between 30 and 40 mm Hg (median: 0.27; interquartile range [IQR]: 0.20-0.37). In contrast, elevated ICP (> 20 mm Hg) and reduced ETCO₂ (20-30 mm Hg) were associated with lower CO₂Rx values (median: 0.09; IQR: - 0.02 to 0.15), suggesting impaired reactivity. A positive correlation emerged between CO₂Rx and cerebral perfusion pressure, peaking at 60-75 mm Hg (r = 0.31; p < 0.001). Patients with favorable outcomes displayed higher CO₂Rx values, especially within optimal ICP and ETCO₂ ranges, whereas lower values were associated with poorer outcomes.

CO₂Rx is a promising marker of cerebrovascular metabolic reactivity in TBI, offering novel insights into the dynamic relationship between ICP and ETCO₂. It may aid in detecting autoregulatory dysfunction and guide individualized strategies for ventilation, CO₂ control, and surgical decisions. Prospective validation is warranted to confirm its clinical relevance.

ClinicalTrials.gov identifier: NCT05043545.