Abstract
OBJECTIVE: This study aimed to investigate the association between cytokines and the severity of acute gastrointestinal injury (AGI) in critically ill patients on day 3 after intensive care unit (ICU) admission. METHODS: This was a single-center, prospective observational cohort study. We collected blood samples for 5 consecutive days and measured interleukin-6 (IL-6), interleukin-10 (IL-10), tumor necrosis factor-alpha (TNF-α), intestinal fatty acid-binding protein (I-FABP), lipopolysaccharide (LPS), and D-lactate levels in critically ill patients with AGI admitted to the ICU. The primary outcome was persistent intestinal failure, defined as AGI grades III-IV on day 3 after ICU admission. A multivariate logistic regression analysis was used to identify independent risk factors for persistent intestinal failure, and an XGBoost model was used to assess the relative importance of predictors for persistent intestinal failure. In addition, we performed a mediation analysis to evaluate the mediating role of cytokines in the association between intestinal permeability (D-lactate) and persistent intestinal failure. RESULTS: A total of 116 patients were included in the final analysis. On day 1 after ICU admission, the levels of plasma biomarkers, such as IL-6, IL-10, TNF-α, I-FABP, LPS, and D-lactate, were significantly higher in the AGI III-IV group than in the AGI I-II group. These biomarkers showed a consistently decreasing trend from day 2 to day 5. The multivariate logistic regression analysis identified IL-6, IL-10, D-Lactate, and the SOFA score as independent predictors of persistent intestinal failure. Using the XGBoost algorithm, we determined the relative importance of predicting persistent intestinal failure on day 3 of ICU admission. In descending order, the key predictors were IL-6 (D1), IL-10 (D1), D-lactate (D1), the SOFA score, and sex. The mediation analysis showed that IL-6, IL-10, and TNF-α partially mediated the association between D-lactate levels and persistent intestinal failure. The respective proportions of their mediating effects were 73.3% for IL-6, 52.1% for IL-10, and 30.1% for TNF-α. CONCLUSION: In critically ill patients with AGI, the levels of cytokines on day 1 after ICU admission were positively associated with persistent intestinal failure during the early acute phase. Cytokines may partially mediate the relationship between intestinal injury and progression to persistent intestinal failure. Controlling the inflammatory response may represent a potential therapeutic strategy for acute gastrointestinal injury. CLINICAL TRIAL REGISTRATION: This study was registered with the Chinese Clinical Trial Registry on 21 February 2022 (Registration ID: ChiCTR2200056858).