High-Protein Enteral Nutrition Enriched With Immune-Modulating Nutrients vs Standard High-Protein Enteral Nutrition and Nosocomial Infections in the ICU: A Randomized Clinical Trial

• Published in: JAMA : the journal of the American Medical Association 2014-08, Vol.312 (5), p.514-524
• Main Authors: van Zanten, Arthur R. H, Sztark, François, Kaisers, Udo X, Zielmann, Siegfried, Felbinger, Thomas W, Sablotzki, Armin R, De Waele, Jan J, Timsit, Jean-François, Honing, Marina L. H, Keh, Didier, Vincent, Jean-Louis, Zazzo, Jean-Fabien, Fijn, Harvey B. M, Petit, Laurent, Preiser, Jean-Charles, van Horssen, Peter J, Hofman, Zandrie
• Format: Article
• Language: English
• Subjects: Adult; Aged; Biological and medical sciences; Clinical outcomes; Critical care; Critical Illness - therapy; Cross Infection - prevention & control; Dietary Proteins - therapeutic use; Double-Blind Method; Enteral Nutrition; Female; General aspects; Human infectious diseases. Experimental studies and models; Humans; Immunomodulation; Infections; Infectious diseases; Intensive Care Units; Intention to Treat Analysis; Length of Stay; Male; Medical sciences; Middle Aged; Multiple Organ Failure; Proteins; Respiration, Artificial
• ISSN: 0098-7484; 1538-3598
• DOI: 10.1001/jama.2014.7698

IMPORTANCE: Enteral administration of immune-modulating nutrients (eg, glutamine, omega-3 fatty acids, selenium, and antioxidants) has been suggested to reduce infections and improve recovery from critical illness. However, controversy exists on the use of immune-modulating enteral nutrition, reflected by lack of consensus in guidelines. OBJECTIVE: To determine whether high-protein enteral nutrition enriched with immune-modulating nutrients (IMHP) reduces the incidence of infections compared with standard high-protein enteral nutrition (HP) in mechanically ventilated critically ill patients. DESIGN, SETTING, AND PARTICIPANTS: The MetaPlus study, a randomized, double-blind, multicenter trial, was conducted from February 2010 through April 2012 including a 6-month follow-up period in 14 intensive care units (ICUs) in the Netherlands, Germany, France, and Belgium. A total of 301 adult patients who were expected to be ventilated for more than 72 hours and to require enteral nutrition for more than 72 hours were randomized to the IMHP (n = 152) or HP (n = 149) group and included in an intention-to-treat analysis, performed for the total population as well as predefined medical, surgical, and trauma subpopulations. INTERVENTIONS: High-protein enteral nutrition enriched with immune-modulating nutrients vs standard high-protein enteral nutrition, initiated within 48 hours of ICU admission and continued during the ICU stay for a maximum of 28 days. MAIN OUTCOMES AND MEASURES: The primary outcome measure was incidence of new infections according to the Centers for Disease Control and Prevention (CDC) definitions. Secondary end points included mortality, Sequential Organ Failure Assessment (SOFA) scores, mechanical ventilation duration, ICU and hospital lengths of stay, and subtypes of infections according CDC definitions. RESULTS: There were no statistically significant differences in incidence of new infections between the groups: 53% (95% CI, 44%-61%) in the IMHP group vs 52% (95% CI, 44%-61%) in the HP group (P = .96). No statistically significant differences were observed in other end points, except for a higher 6-month mortality rate in the medical subgroup: 54% (95% CI, 40%-67%) in the IMHP group vs 35% (95% CI, 22%-49%) in the HP group (P = .04), with a hazard ratio of 1.57 (95% CI, 1.03-2.39; P = .04) for 6-month mortality adjusted for age and Acute Physiology and Chronic Health Evaluation II score comparing the groups. CONCLUSIONS AND RELEVANCE: Among adult