Temporal Discordance of the Inflammation, Catabolism and Immunosuppression Triad in Chronic Critical Illness

Background and Objectives: Chronic critical illness (CCI) is a growing problem in modern intensive care, though its pathophysiology remains incompletely defined. While the ICS triad is thought to perpetuate organ dysfunction, the temporal interplay between its components has not been studied. The objective was to characterize the temporal dynamics of each component and to assess their synchrony in CCI patients. Materials and Methods: This retrospective cohort study analyzed data from the Russian Intensive Care Dataset (RICD v3.0). Adult ICU patients with at least one documented ICS episode (CRP > 20 mg/L, albumin < 30 g/L, lymphocytes < 0.8 × 10⁹/L within 24 h) were included. Daily binary statuses were generated for each domain using an episode-persistence algorithm. Pairwise concordance was assessed using Cohen's κ with bootstrap resampling and generalized estimating equation (GEE) models; domain burden, episode frequency, and status combinations were also evaluated. Results: A total of 820 CCI patients contributed 18,525 non-critical patient-days. CRP and albumin domains were persistently positive (median burden 100% both), while lymphocyte positivity was brief (median burden 34.2%) and recurrent (≥2 episodes in 45.1%). CRP and lymphocyte domains were discordant in 81.2% of days (κ = -0.024; OR 0.60; Holm-adjusted p = 0.005); lymphocyte and albumin domains in 77.0% (κ = -0.021; OR 0.49; Holm-adjusted p < 0.001). CRP and albumin were largely concordant (78.5%; κ = 0.299; OR 2.71; Holm-adjusted p < 0.001). Isolated lymphopenia was rare (0.6%), whereas complete compensation was seen in 7.7% of observations. Conclusions: These findings suggest that the ICS triad components follow distinct, temporally discordant trajectories after CCI onset, questioning the view of CCI as a unified state. While periods of complete compensation were observed, their relationship to clinical resolution of CCI requires further investigation.