title: 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.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  METHODS
  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.
  
  
  METHODS
  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
  Among adult patients breathing with the aid of mechanical ventilation in the ICU, IMHP compared with HP did not improve infectious complications or other clinical end points and may be harmful as suggested by increased adjusted mortality at 6 months. These findings do not support the use of IMHP nutrients in these patients.
  
  
  BACKGROUND
  trialregister.nl Identifier: NTR2181.
authors.affiliation: Gelderse Vallei Hospital, Ede, the Netherlands.
authors.forename: Arthur R H
authors.initials: AR
authors.lastname: van Zanten
authors.affiliation: Groupe Hôpital Pellegrin - CHU Bordeaux, Bordeaux, France.
authors.forename: François
authors.initials: F
authors.lastname: Sztark
authors.affiliation: Universitätsklinikum Leipzig, Germany.
authors.forename: Udo X
authors.initials: UX
authors.lastname: Kaisers
authors.affiliation: Heinrich-Braun-Klinikum, Zwickau, Germany.
authors.forename: Siegfried
authors.initials: S
authors.lastname: Zielmann
authors.affiliation: Klinikum Neuperlach, Munich, Germany.
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Felbinger
authors.affiliation: Klinikum St Georg, Leipzig, Germany.
authors.forename: Armin R
authors.initials: AR
authors.lastname: Sablotzki
authors.affiliation: Ghent University Hospital, Ghent, Belgium.
authors.forename: Jan J
authors.initials: JJ
authors.lastname: De Waele
authors.affiliation: Hôpital Universitaire Albert Michallon, Grenoble, France.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Timsit
authors.affiliation: Medisch Centrum Alkmaar, Alkmaar, the Netherlands.
authors.forename: Marina L H
authors.initials: ML
authors.lastname: Honing
authors.affiliation: Charité Universitätsmedizin Berlin, Germany.
authors.forename: Didier
authors.initials: D
authors.lastname: Keh
authors.affiliation: Erasme University Hospital, Université libre de Bruxelles, Brussels, Belgium.
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Vincent
authors.affiliation: Hôpital Antoine-Béclère, Clamart, France.
authors.forename: Jean-Fabien
authors.initials: JF
authors.lastname: Zazzo
authors.affiliation: Gelderse Vallei Hospital, Ede, the Netherlands.
authors.forename: Harvey B M
authors.initials: HB
authors.lastname: Fijn
authors.affiliation: Groupe Hôpital Pellegrin - CHU Bordeaux, Bordeaux, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Petit
authors.affiliation: Erasme University Hospital, Université libre de Bruxelles, Brussels, Belgium.
authors.forename: Jean-Charles
authors.initials: JC
authors.lastname: Preiser
authors.affiliation: Nutricia Advanced Medical Nutrition, Nutricia Research, Utrecht, the Netherlands.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: van Horssen
authors.affiliation: Nutricia Advanced Medical Nutrition, Nutricia Research, Utrecht, the Netherlands.
authors.forename: Zandrie
authors.initials: Z
authors.lastname: Hofman
mesh_terms: D000328:Adult; D000368:Aged; D016638:Critical Illness / Q000628:therapy; D003428:Cross Infection / Q000517:prevention & control*; D004044:Dietary Proteins / Q000627:therapeutic use*; D004311:Double-Blind Method; D004750:Enteral Nutrition; D005260:Female; D006801:Humans; D056747:Immunomodulation; D007362:Intensive Care Units; D057194:Intention to Treat Analysis; D007902:Length of Stay; D008297:Male; D008875:Middle Aged; D009102:Multiple Organ Failure; D012121:Respiration, Artificial
chemical_list: D004044:Dietary Proteins