Early enteral nutrition increases 28-day mortality in patients with sepsis who are on invasive mechanical ventilation: A retrospective analysis based on the MIMIC - IV database

Abstract Background: The optimal timing of enteral nutrition for critically ill septic patients in the intensive care unit (ICU) who require invasive mechanical ventilation has not been determined, and the influence of early enteral nutrition on clinical outcomes is unclear. Methods: This retrospective observational study utilized data from the Medical Information Mart for Intensive Care IV 2.2 (MIMIC-IV 2.2) database to investigate patients with sepsis who needed invasive mechanical ventilation post-ICU admission. Patients who had enteral nutrition (EN) initiated within 72 hours of ICU were categorized into the early enteral nutrition (EEN) group, while those who began enteral nutrition after 72 hours were placed in the delayed enteral nutrition (DEN) group. Propensity score matching analysis was performed to compare outcomes between these two groups, with the primary outcome being 28-day mortality. Results:The final analysis included 2293 patients, 1546 (67.4%) of whom received enteral nutrition within 72 hours of invasive mechanical ventilation. The overall 28-day mortality rate was 31.0%. After propensity score matching employing the proximity matching method, Cox survival analysis revealed that early enteral nutrition was associated with increased 28-day mortality in septic patients on invasive mechanical ventilation (hazard ratio(HR) 1.440 , 95% CI 1.179–1.760; p ＜0.001). The sensitivity and robustness of the evaluation results under different models, including optimal matching (adjusted odds ratio（aOR） 1.54, 95% CI 1.22–1.93, p < 0.001), inverse probability of treatment weighting (aOR 1.27, 95% CI 1.02–1.58, p = 0.035), and logistic regression analysis (aOR 1.48, 95% CI 1.18–1.84, p = 0.001), confirmed the detrimental effects of early enteral nutrition on invasive mechanical ventilation in septic patients. Subgroup analyses of the original data indicated that early enteral nutrition may be particularly harmful in mechanically ventilated septic shock patients and severely ill young female patients. Conclusions: Compared to delayed enteral nutrition, early enteral nutrition increases 28-day mortality in septic patients on invasive mechanical ventilation, especially in septic shock patients and severely ill young female patients on invasive mechanical ventilation. Randomized controlled trials are warranted to compare the efficacy of early and delayed enteral nutrition in septic patients requiring invasive mechanical ventilation.