Enhanced exclusive enteral nutrition delivery during the first 7 days is associated with decreased 28-day mortality in critically ill patients with normal lactate level: a post hoc analysis of a multicenter randomized trial

Background and aims Exclusive enteral nutrition (EN) is often observed during the first week of ICU admission because of the extra costs and safety considerations for early parenteral nutrition. This study aimed to assess the association between nutrition intake and 28-day mortality in critically ill patients receiving exclusive EN. Methods This is a post hoc analysis of a cluster-randomized clinical trial that assesses the effect of implementing a feeding protocol on mortality in critically ill patients. Patients who stayed in the ICUs for at least 7 days and received exclusive EN were included in this analysis. Multivariable Cox hazard regression models and restricted cubic spline models were used to assess the relationship between the different doses of EN delivery and 28-day mortality. Subgroups with varying lactate levels at enrollment were additionally analyzed to address the potential confounding effect brought in by the presence of shock-related hypoperfusion. Results Overall, 1322 patients were included in the analysis. The median (interquartile range) daily energy and protein delivery during the first week of enrollment were 14.6 (10.3–19.6) kcal/kg and 0.6 (0.4–0.8) g/kg, respectively. An increase of 5 kcal/kg energy delivery was associated with a significant reduction (approximately 14%) in 28-day mortality (adjusted hazard ratio [HR] = 0.865, 95% confidence interval [CI]: 0.768–0.974, P = 0.016). For protein intake, a 0.2 g/kg increase was associated with a similar mortality reduction with an adjusted HR of 0.868 (95% CI 0.770–0.979). However, the benefits associated with enhanced nutrition delivery could be observed in patients with lactate concentration ≤ 2 mmol/L (adjusted HR = 0.804 (95% CI 0.674–0.960) for energy delivery and adjusted HR = 0.804 (95% CI 0.672–0.962) for protein delivery, respectively), but not in those > 2 mmol/L. Conclusions During the first week of critical illness, enhanced nutrition delivery is associated with reduced mortality in critically ill patients receiving exclusive EN, only for those with lactate concentration ≤ 2 mmol/L. Trial registration : ISRCTN12233792, registered on November 24, 2017.