Critical Episodes of Inflammation, Catabolism, and Immunosuppression Define Mortality Risk in Chronic Critical...

Background/Objectives: A globally recognized definition of chronic critical illness (CCI) is lacking. Temporal criteria produce variable estimates, while pathophysiological models emphasize inflammation, catabolism, and immunosuppression (ICS). The relationship between ICS dynamics and mortality remains unclear. Methods: This retrospective single-center cohort study analyzed real-world data from 3374 adult intensive care unit (ICU) patients. CCI was defined by first detection of the ICS triad: C-reactive protein (CRP) >20 mg/L, albumin <30 g/L, and absolute lymphocyte count <0.8 × 10⁹/L within 24 h. CCI days were classified as critical or non-critical. Mortality and mortality density were compared across CCI groups and periods. Results: CCI developed in 820 patients (24.3%) and was associated with higher mortality (relative risk (RR) 5.08) and mortality density (incidence rate ratio (IRR) 4.09). Critical periods comprised 22.15% of CCI patient-days and had higher mortality density than non-critical periods (IRR 4.25) and no CCI (IRR 10.10). Conclusions: CCI appears to be a biologically dynamic condition characterized by alternating critical and non-critical periods. Periods of simultaneous inflammation, catabolism, and immunosuppression are associated with the highest mortality density, while elevated mortality persists even during periods of partial biological compensation. These findings support the concept that the current ICS state may reflect clinically relevant changes in the course of CCI. However, they do not establish diagnostic or predictive performance and require external validation.