Early enteral immunonutrition in patients with severe sepsis - Results of an interim analysis of a randomized multicentre clinical trial

Objective: To compare the mortality of critically ill patients given either enteral feeding with an immune-enhancing formula or parenteral nutrition (PN). We report the results of a planned interim analysis on patients with severe sepsis which was undertaken earlier than planned once a meta-analysis suggested:excess mortality in patients with severe sepsis given enteral immunonutrition. Design: Randomised multicentre unblinded controlled clinical trial. Setting Thirty-three General Intensive Care Units in Italy. Patients and participants: Among the 237 recruited patients, 39 had severe sepsis or septic shock; 21 of them received PN. Interventions: Eligible patients received either total PN or enteral nutrition, the latter containing extra L-arginine, omega-3 fatty acids, vitamin E, beta carotene, zinc, and selenium. Measurements and results: The primary endpoint for the subgroup analysis on patients with severe sepsis was mortality on Intensive Care Unit (ICU). The ICU mortality of patients with severe sepsis given enteral nutrition (EN) was higher than for those given PN (44.4% vs 14.3%; p=0.039). More patients given EN than patients given PN still had severe sepsis when they died (38.9% vs 9.5%, p=0.055). Recruitment of patients with severe sepsis was subsequently stopped. Conclusions: Our results show that enteral immunonutrition, compared to PN, may be associated with excess mortality in patients with severe sepsis.