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

Background: 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). Methods: 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. Results: 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. Conclusions: 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. Clinical Trial registration: ClinicalTrials.gov identifier: NCT05043545.