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A novel index for trending sepsis and inflammatory response using processed EEG and Heart Rate Variability
Jaume Millán I Ichon1,2, Montserrat Vallverdú-Ferrer3, Erik Weber Jensen4,5
1Institute for Research and Innovation in Health (IRIS), School of Industrial Engineering of Barcelona (ETSEIB), Universitat Politècnica de Catalunya (UPC), CIBER of Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Barcelona, Spain. jaume.millan.i@upc.edu.
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Early detection of systemic inflammation and sepsis is essential for improving patient outcomes. Heart rate variability (HRV) has been proposed as a non-invasive marker of inflammation; however, its specificity is limited, particularly under anesthesia or sedation. This study introduces the Trend of Sepsis and Inflammation (TSI), a novel index combining HRV and electroencephalogram (EEG)-derived parameters to better isolate inflammation-related autonomic changes.A post-hoc observational analysis was conducted in two cohorts: surgical patients undergoing general anesthesia (N = 41) and septic patients admitted to the intensive care unit (N = 21). Continuous EEG and ECG recordings were obtained using a multimodal monitoring system. HRV parameters from time and frequency domains, together with an EEG-derived Brain Activity Index, were integrated using an Adaptive Neuro-Fuzzy Inference System (ANFIS) to compute the TSI. TSI values were compared across three conditions: awake baseline, post-surgical inflammation, and sepsis. Statistical analysis employed non-parametric tests, while discriminative performance was assessed using prediction probability (Pk) and concordance with predefined interpretation ranges.TSI values increased progressively across conditions. Median values were 2.29 (IQR: 0.00-13.74) at baseline, 24.68 (18.50-32.00) post-surgery, and 65.59 (52.38-76.25) in sepsis, with significant differences (p < 0.0001). The TSI demonstrated strong discriminative ability (Pk = 93.58%) and high overall concordance (92.6%). HRV spectrograms and EEG-compensated analyses supported physiological consistency.The TSI distinguishes between baseline, post-surgical inflammatory, and septic states. By compensating for anesthesia-related autonomic suppression, it provides a continuous, non-invasive measure of inflammatory burden, supporting its potential use in perioperative and critical care settings. Further validation against established biomarkers is warranted.