Mortality-associated high-risk phenotype in paediatric persistent inflammation, immunosuppression, and catabolism syndrome: single-centre retrospective cohort study, 2019–2024

Persistent inflammation, immunosuppression, and catabolism syndrome (PICS) is increasingly recognised as a critical contributor to adverse outcomes in critically ill patients, yet its clinical implications in paediatric populations remain under-explored. The aim of this study was to apply the established PICS diagnostic criteria to a cohort in a paediatric intensive care unit (PICU) to identify clinical factors associated with mortality and characterise phenotype with distinct outcomes. We conducted a retrospective analysis of 536 PICU patients admitted for ≥ 15 days between 2019 and 2024 at a single tertiary centre. Paediatric PICS was defined as elevated C-reactive protein (> 2.0 mg·dL–1), hypoalbuminaemia (< 3.0 g·dL–1), and lymphopenia (< 800 µL–1) on days 13–15. Twenty-two clinical variables measured at or around day 14 were analysed using principal component analysis (PCA) followed by k-means clustering of retained principal component scores. Weighted clustering using the original variables was performed as a sensitivity analysis. Survival differences between PCA-derived phenotypes were assessed using Kaplan–Meier analysis. Paediatric PICS was diagnosed in 64 patients (11.9%), who exhibited higher mortality rates (42% vs. 15%). PCA-based clustering identified three clusters (interpreted as phenotypes) with distinct mortality gradients. The first principal component represented a high-risk axis characterised by greater organ dysfunction, hyperbilirubinaemia, coagulopathy, metabolic derangement, and thrombocytopenia. A concordant high-risk phenotype was reproduced in the weighted-clustering sensitivity analysis. In the PCA-based main analysis, 1-year survival differed significantly across three clusters (log-rank χ² = 11.85, P = 0.0027). Paediatric PICS appears to be phenotypically heterogeneous and may include higher-risk phenotypes. These findings are exploratory and require external validation before clinical implementation.