Methodological Definition and Validation of the Intracranial Pressure-End-Tidal CO2 Slope (IESlope): Characterization and Clinical Relevance in Traumatic Brain Injury
Marco Bonfanti, Rosalia Zangari, Ferdinando L. Lorini, Tommaso Togni, Fabio Micheli, Andrea Briolini, Luigi A. Lanterna, Simona Serioli, Rita Bertuletti, Simonetta Gerevini, Ezio Bonanomi, Francesco Biroli, Paolo GrittiBackground:
The metabolic component of cerebral autoregulation is crucial in traumatic brain injury (TBI), yet continuously monitored indices are limited. This study introduces the ICP-EtCO 2 Slope (IESlope), quantifying the dynamic relationship between end-tidal CO 2 (EtCO 2 ) and intracranial pressure (ICP), and evaluates its association with 12-month mortality and unfavorable outcome (Glasgow Outcome Scale-Extended, GOSE≤4). Second, IESlope visualization and its ability to predict short-term ICP changes during EtCO 2 variations are assessed.
Methods:
Intensive care unit records of 218 adult and pediatric TBI patients were retrospectively analyzed (median age 44, IQR: 24-66; 76% male). IESlope was calculated as the angle of the linear regression between EtCO 2 and ICP over 60-minute moving windows and visualized using streamline mapping (ICP-EtCO 2 space). IESlope values were averaged to obtain a single patient-level metric used in univariate and multivariable analyses (area under the curve, AUC). Predictive capability was assessed by comparing predicted versus observed ICP changes at 5, 10, and 20 minutes during significant EtCO 2 variations.
Results:
Lower IESlope values were associated with mortality and GOSE≤4 (median: 7.76 vs. 14.8 and 10.5 vs. 18.6, respectively,
Conclusions:
IESlope provides a continuous, quantitative measure of CO 2 -related ICP reactivity and may support individualized ventilatory management in TBI, pending prospective validation.