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Observational Study
. 2025 Jun;39(3):581-594.
doi: 10.1007/s10877-025-01285-z. Epub 2025 Mar 22.

Continuous monitoring of intracranial pressure and end tidal carbon dioxide variations in traumatic brain injury: introducing the carbon dioxide reactivity index (CO2Rx)

Paolo Gritti  1 , Marco Bonfanti  2 , Rosalia Zangari  2 , Ezio Bonanomi  3 , Maria Di Matteo  3 , Davide Corbella  3 , Alessia Farina  3 , Lorenzo Lecchi  4 , Tommaso Togni  3 , Pietro Mandelli  3 , Luigi Andrea Lanterna  5 , Francesco Biroli  2 , Ferdinando Luca Lorini  3
Affiliations
Observational Study

Continuous monitoring of intracranial pressure and end tidal carbon dioxide variations in traumatic brain injury: introducing the carbon dioxide reactivity index (CO2Rx)

Paolo Gritti et al. J Clin Monit Comput. 2025 Jun.

Abstract

Purpose: The continuous monitoring of cerebral metabolic autoregulation in patients with severe traumatic brain injury (TBI) is poorly documented in the literature and largely absent from clinical practice. This study aimed to assess whether variations in intracranial pressure (ICP) and end-tidal carbon dioxide (ETCO2) can form the basis of an index for cerebrovascular autoregulation reactivity, and whether this index can improve the prediction of clinical outcomes in both adult and pediatric TBI patients.

Methods: Data from adult and pediatric patients with severe TBI were retrospectively analyzed. The Carbon Dioxide Reactivity Index (CO2Rx) was introduced as a novel tool to assess cerebrovascular reactivity in response to variations in CO2 and ICP. CO2Rx was calculated by analyzing the relationship between ICP and ETCO2, sampled at approximately 5-minute intervals, using linear correlation within moving time windows ranging from 40 to 180 min in 10-minute increments. The discriminatory power of CO2Rx in predicting clinical outcomes was evaluated through Receiver Operating Characteristic (ROC) curve analysis. The primary outcome measures included in-hospital mortality and the 12-month Glasgow Outcome Scale-Extended (GOSE) score.

Results: The study included 218 TBI patients (40 pediatric and 178 adult). CO2Rx values showed a significant correlation with outcomes, with a CO2Rx threshold of 0.28 effectively distinguishing between favorable and unfavorable outcomes. For the fatal/non-fatal outcome, the CO2Rx crude model alone had an Area Under the Curve (AUC) of 0.737. When combined with other predictors (Impact Core + ICP + CO2Rx), this model achieved the highest AUC of 0.929.

Conclusion: CO2Rx demonstrated significant predictive value for mortality and unfavorable outcomes in TBI patients, serving as a continuous index of cerebrovascular reactivity to CO2. It holds potential to improve severe TBI management by optimizing the interaction between ventilation and metabolic autoregulation.

Trial registration: ClinicalTrials.gov Identifier: NCT NCT05043545.

Keywords: Carbon dioxide reactivity index (CO2Rx); Cerebral autoregulation; Cerebrovascular reactivity; End-tidal carbon dioxide (ETCO2); Intracranial pressure (ICP); Traumatic brain injury (TBI).

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: All procedures involving human participants complied with the ethical standards of the institutional and/or national research committee, as well as the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. This study received approval from the Bergamo Ethics Committee on February 22, 2021, with an amendment on December 27, 2021 (reference number: 303/20). Researchers accessed only anonymized data, and formal consent was not required for this type of study. The study adhered to the Standards for Reporting of Diagnostic Accuracy Studies (STARD) and the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines. Competing interests: The authors declare no competing interests.

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