Which critically ill patients are more susceptible to the adverse effects associated with feeding intolerance? A secondary analysis of a cluster-randomized controlled trial

Objective It remains unclear which critically ill patients are more susceptible to the adverse effects associated with feeding intolerance (FI), which is common in patients receiving early enteral nutrition (EEN). Therefore, we aimed to explore the association between FI and short-term outcomes in critically ill patients receiving EEN. Methods This secondary analysis of a multicenter cluster-randomized controlled trial included patients who initiated enteral nutrition within 48 h of admission and received it for at least 3 days. We utilized univariate and multivariate propensity score-weighted logistic regression analyses to investigate the association between FI and 28-day mortality. We conducted multiple subgroup analyses to identify subcohorts that are more likely to be adversely impacted by FI. Results A total of 1,545 patients were included in the final analysis, among whom 856 experienced FI and 689 did not. In univariate analyses, no association was found between FI and 28-day mortality [odds ratio (OR) 1.302, 95% CI 0.967–1.752, p = 0.082]. After multiple adjustment, we found the occurrence of FI was associated with higher 28-day mortality [adjusted OR (aOR) 1.370, 95% CI 1.002–1.873, p = 0.048]. This finding was consistent in the propensity-weighted model (aOR 1.370, 95% CI 1.010–1.873, p = 0.015). In multivariate analyses, larger effect estimates were observed among patients aged over 65 years (aOR 1.544, 95% CI 1.019–2.338, p = 0.04), with a normal body mass index (BMI) (aOR 1.523, 95% CI 1.065–2.177, p = 0.021), with a primary diagnosis of respiratory disease (aOR 1.822, 95% CI 1.149–2.891, p = 0.011), and with a sequential organ failure assessment (SOFA) score of ≤ 8 (aOR 1.864, 95% CI 1.204–2.885, p = 0.005). Conclusion In critically ill patients receiving EEN, FI was associated with higher 28-day mortality, longer ICU LOS, fewer ventilator-free days and ICU-free days. Elderly patients, those with a normal BMI, those with a primary diagnosis of respiratory diseases, and those with a SOFA score of ≤ 8 may be more susceptible to adverse effects of FI. However, these subgroup findings should be interpreted cautiously given multiple comparisons.