Early Oral/Enteral Feeding and Rehabilitation Are Associated With Lower PIICS Incidence: A Propensity Score‐Matched Single Center Study

ABSTRACT Objective Persistent inflammation, immunosuppression, and catabolism syndrome (PIICS) is a pathophysiological condition that may underlie poor long‐term outcomes after critical illness. We investigated whether the early combined initiation of oral/enteral feeding and rehabilitation is associated with the development of PIICS. Methods We Retrospectively Analyzed Patients Admitted to the Emergency ICU of Osaka University Hospital During 2016–2024. PIICS Was Diagnosed on Hospital Day 14 (±3 Days) Based on CRP > 2.0 mg/ dL , Lymphocytes < 800/ μL , and Albumin < 3.0 g/ dL , With ≥ 2 of 3 Criteria Required for Diagnosis. Early Combined Intervention Was Defined as Oral/Enteral Feeding Initiation Within 3 Days and Rehabilitation Within 7 Days of ICU Admission. Missing SOFA Scores (45.3%) Were Multiply Imputed by Predictive Mean Matching (m = 50). Propensity Score Matching Was Performed Within Each Imputed Dataset Using a Within‐Imputation Approach, With Estimates Pooled Using Rubin's Rules. Results Among 5709 ICU Patients, 2860 Were Eligible for the Primary Analysis. Early Combined Intervention Was Initiated in 348 (12.2%). Propensity Score Matching Generated an Average of 347 Pairs Per Imputed Dataset (Range: 333–348). Early Combined Intervention Was Associated With Lower PIICS Incidence ( OR = 0.481, 95% CI 0.337–0.686, p < 0.001). Significance Was Retained in the Sensitivity Analysis Restricted to Patients With Observed SOFA Scores (Complete‐Case Analysis, n = 1512; OR = 0.533, 95% CI 0.340–0.836, p < 0.001). Conclusion Early combined initiation of oral/enteral feeding and rehabilitation was associated with lower PIICS incidence in critically ill patients, suggesting the value of integrated multimodal supportive care for PIICS prevention and providing a rationale for prospective multicenter studies to establish causality.