Persistent inflammation, immunosuppression and catabolism syndrome and malnutrition in critically ill patients with sepsis: A multi-center prospective observational study

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BACKGROUND AND AIMS: Persistent Inflammation, Immunosuppression, and Catabolism Syndrome (PIICS) was introduced as a clinical endotype of chronic critical illness and is frequently observed in patients with sepsis. Although nutritional therapy may affect immune function and disease progression, the relationship between malnutrition, nutritional delivery, and PIICS remains unclear. We herein investigated the incidence and outcomes of PIICS and examined its relationship with acute-phase nutritional therapy and Global Leadership Initiative on Malnutrition (GLIM) malnutrition in intensive care unit (ICU) patients with sepsis. METHODS: This was a secondary analysis of the multicenter prospective ILOSS study including adult (≥18 years) ICU patients with sepsis admitted between 2020 and 2021. PIICS was defined as a hospital stay ≥14 days and at least two of the following on day 14: lymphocyte count <800/μL, C-reactive protein >2.0 mg/dL, and albumin <3.0 g/dL. Malnutrition was defined using GLIM criteria. The primary outcome was the composite of in-hospital mortality or severe functional dependence, defined as Barthel index <60 at hospital discharge. A multivariable logistic regression analysis identified risk factors for PIICS, and energy and protein intakes on days 1-14 were compared between the PIICS and non-PIICS groups. RESULTS: Among 250 patients, 127 (50.8%) developed PIICS. The PIICS group had higher SOFA scores on ICU admission and the higher use of mechanical ventilation and renal replacement therapy during the ICU stay. GLIM malnutrition was more prevalent in the PIICS group. The primary outcome was more frequent in patients with PIICS at discharge (56.7% vs. 32.8%) and at 12 months (55.7% vs. 31.4%). GLIM malnutrition was independently associated with PIICS (OR 1.80, 95% CI 1.02-3.18; p = 0.04). Among patients without GLIM malnutrition at admission, energy and protein intakes on days 8-14 were lower in patients who subsequently developed PIICS. CONCLUSION: Approximately 50% of ICU patients with sepsis developed PIICS. Patients with PIICS had higher mortality and worse physical function and quality of life after discharge, although these differences attenuated over time. Pre-existing GLIM malnutrition seemed to be associated with an increased risk of developing PIICS. A causal relationship between nutritional delivery and PIICS development in patients with/without malnutrition requires further investigation.

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