Early Oral/Enteral Feeding and Rehabilitation Are Associated With Lower PIICS Incidence: A Propensity Score-Matched...

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.

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.

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).

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.