title: Early versus Late Parenteral Nutrition in Critically Ill Children.
abstract: BACKGROUND
  Recent trials have questioned the benefit of early parenteral nutrition in adults. The effect of early parenteral nutrition on clinical outcomes in critically ill children is unclear.
  
  
  METHODS
  We conducted a multicenter, randomized, controlled trial involving 1440 critically ill children to investigate whether withholding parenteral nutrition for 1 week (i.e., providing late parenteral nutrition) in the pediatric intensive care unit (ICU) is clinically superior to providing early parenteral nutrition. Fluid loading was similar in the two groups. The two primary end points were new infection acquired during the ICU stay and the adjusted duration of ICU dependency, as assessed by the number of days in the ICU and as time to discharge alive from ICU. For the 723 patients receiving early parenteral nutrition, parenteral nutrition was initiated within 24 hours after ICU admission, whereas for the 717 patients receiving late parenteral nutrition, parenteral nutrition was not provided until the morning of the 8th day in the ICU. In both groups, enteral nutrition was attempted early and intravenous micronutrients were provided.
  
  
  RESULTS
  Although mortality was similar in the two groups, the percentage of patients with a new infection was 10.7% in the group receiving late parenteral nutrition, as compared with 18.5% in the group receiving early parenteral nutrition (adjusted odds ratio, 0.48; 95% confidence interval [CI], 0.35 to 0.66). The mean (±SE) duration of ICU stay was 6.5±0.4 days in the group receiving late parenteral nutrition, as compared with 9.2±0.8 days in the group receiving early parenteral nutrition; there was also a higher likelihood of an earlier live discharge from the ICU at any time in the late-parenteral-nutrition group (adjusted hazard ratio, 1.23; 95% CI, 1.11 to 1.37). Late parenteral nutrition was associated with a shorter duration of mechanical ventilatory support than was early parenteral nutrition (P=0.001), as well as a smaller proportion of patients receiving renal-replacement therapy (P=0.04) and a shorter duration of hospital stay (P=0.001). Late parenteral nutrition was also associated with lower plasma levels of γ-glutamyltransferase and alkaline phosphatase than was early parenteral nutrition (P=0.001 and P=0.04, respectively), as well as higher levels of bilirubin (P=0.004) and C-reactive protein (P=0.006).
  
  
  CONCLUSIONS
  In critically ill children, withholding parenteral nutrition for 1 week in the ICU was clinically superior to providing early parenteral nutrition. (Funded by the Flemish Agency for Innovation through Science and Technology and others; ClinicalTrials.gov number, NCT01536275.).
authors.affiliation: From the Department of Cellular and Molecular Medicine, Clinical Division and Laboratory of Intensive Care Medicine, KU Leuven University Hospital, Leuven, Belgium (T.F., D.M., P.J.W., I.V., Y.D., D.V., L.D., M.P.C., J.H., G.V.B.); the Department of Pediatrics and Pediatric Surgery, Intensive Care, Erasmus-MC Sophia Children's Hospital, Rotterdam, the Netherlands (D.K., S.V., D.T., K.J.); and the Department of Pediatrics, Intensive Care Unit, University of Alberta, Stollery Children's Hospital, Edmonton, Canada (G.G.G., J.H., A.J.).
authors.forename: Tom
authors.initials: T
authors.lastname: Fivez
authors.affiliation: From the Department of Cellular and Molecular Medicine, Clinical Division and Laboratory of Intensive Care Medicine, KU Leuven University Hospital, Leuven, Belgium (T.F., D.M., P.J.W., I.V., Y.D., D.V., L.D., M.P.C., J.H., G.V.B.); the Department of Pediatrics and Pediatric Surgery, Intensive Care, Erasmus-MC Sophia Children's Hospital, Rotterdam, the Netherlands (D.K., S.V., D.T., K.J.); and the Department of Pediatrics, Intensive Care Unit, University of Alberta, Stollery Children's Hospital, Edmonton, Canada (G.G.G., J.H., A.J.).
authors.forename: Dorian
authors.initials: D
authors.lastname: Kerklaan
authors.affiliation: From the Department of Cellular and Molecular Medicine, Clinical Division and Laboratory of Intensive Care Medicine, KU Leuven University Hospital, Leuven, Belgium (T.F., D.M., P.J.W., I.V., Y.D., D.V., L.D., M.P.C., J.H., G.V.B.); the Department of Pediatrics and Pediatric Surgery, Intensive Care, Erasmus-MC Sophia Children's Hospital, Rotterdam, the Netherlands (D.K., S.V., D.T., K.J.); and the Department of Pediatrics, Intensive Care Unit, University of Alberta, Stollery Children's Hospital, Edmonton, Canada (G.G.G., J.H., A.J.).
authors.forename: Dieter
authors.initials: D
authors.lastname: Mesotten
authors.affiliation: From the Department of Cellular and Molecular Medicine, Clinical Division and Laboratory of Intensive Care Medicine, KU Leuven University Hospital, Leuven, Belgium (T.F., D.M., P.J.W., I.V., Y.D., D.V., L.D., M.P.C., J.H., G.V.B.); the Department of Pediatrics and Pediatric Surgery, Intensive Care, Erasmus-MC Sophia Children's Hospital, Rotterdam, the Netherlands (D.K., S.V., D.T., K.J.); and the Department of Pediatrics, Intensive Care Unit, University of Alberta, Stollery Children's Hospital, Edmonton, Canada (G.G.G., J.H., A.J.).
authors.forename: Sascha
authors.initials: S
authors.lastname: Verbruggen
authors.affiliation: From the Department of Cellular and Molecular Medicine, Clinical Division and Laboratory of Intensive Care Medicine, KU Leuven University Hospital, Leuven, Belgium (T.F., D.M., P.J.W., I.V., Y.D., D.V., L.D., M.P.C., J.H., G.V.B.); the Department of Pediatrics and Pediatric Surgery, Intensive Care, Erasmus-MC Sophia Children's Hospital, Rotterdam, the Netherlands (D.K., S.V., D.T., K.J.); and the Department of Pediatrics, Intensive Care Unit, University of Alberta, Stollery Children's Hospital, Edmonton, Canada (G.G.G., J.H., A.J.).
authors.forename: Pieter J
authors.initials: PJ
authors.lastname: Wouters
authors.affiliation: From the Department of Cellular and Molecular Medicine, Clinical Division and Laboratory of Intensive Care Medicine, KU Leuven University Hospital, Leuven, Belgium (T.F., D.M., P.J.W., I.V., Y.D., D.V., L.D., M.P.C., J.H., G.V.B.); the Department of Pediatrics and Pediatric Surgery, Intensive Care, Erasmus-MC Sophia Children's Hospital, Rotterdam, the Netherlands (D.K., S.V., D.T., K.J.); and the Department of Pediatrics, Intensive Care Unit, University of Alberta, Stollery Children's Hospital, Edmonton, Canada (G.G.G., J.H., A.J.).
authors.forename: Ilse
authors.initials: I
authors.lastname: Vanhorebeek
authors.affiliation: From the Department of Cellular and Molecular Medicine, Clinical Division and Laboratory of Intensive Care Medicine, KU Leuven University Hospital, Leuven, Belgium (T.F., D.M., P.J.W., I.V., Y.D., D.V., L.D., M.P.C., J.H., G.V.B.); the Department of Pediatrics and Pediatric Surgery, Intensive Care, Erasmus-MC Sophia Children's Hospital, Rotterdam, the Netherlands (D.K., S.V., D.T., K.J.); and the Department of Pediatrics, Intensive Care Unit, University of Alberta, Stollery Children's Hospital, Edmonton, Canada (G.G.G., J.H., A.J.).
authors.forename: Yves
authors.initials: Y
authors.lastname: Debaveye
authors.affiliation: From the Department of Cellular and Molecular Medicine, Clinical Division and Laboratory of Intensive Care Medicine, KU Leuven University Hospital, Leuven, Belgium (T.F., D.M., P.J.W., I.V., Y.D., D.V., L.D., M.P.C., J.H., G.V.B.); the Department of Pediatrics and Pediatric Surgery, Intensive Care, Erasmus-MC Sophia Children's Hospital, Rotterdam, the Netherlands (D.K., S.V., D.T., K.J.); and the Department of Pediatrics, Intensive Care Unit, University of Alberta, Stollery Children's Hospital, Edmonton, Canada (G.G.G., J.H., A.J.).
authors.forename: Dirk
authors.initials: D
authors.lastname: Vlasselaers
authors.affiliation: From the Department of Cellular and Molecular Medicine, Clinical Division and Laboratory of Intensive Care Medicine, KU Leuven University Hospital, Leuven, Belgium (T.F., D.M., P.J.W., I.V., Y.D., D.V., L.D., M.P.C., J.H., G.V.B.); the Department of Pediatrics and Pediatric Surgery, Intensive Care, Erasmus-MC Sophia Children's Hospital, Rotterdam, the Netherlands (D.K., S.V., D.T., K.J.); and the Department of Pediatrics, Intensive Care Unit, University of Alberta, Stollery Children's Hospital, Edmonton, Canada (G.G.G., J.H., A.J.).
authors.forename: Lars
authors.initials: L
authors.lastname: Desmet
authors.affiliation: From the Department of Cellular and Molecular Medicine, Clinical Division and Laboratory of Intensive Care Medicine, KU Leuven University Hospital, Leuven, Belgium (T.F., D.M., P.J.W., I.V., Y.D., D.V., L.D., M.P.C., J.H., G.V.B.); the Department of Pediatrics and Pediatric Surgery, Intensive Care, Erasmus-MC Sophia Children's Hospital, Rotterdam, the Netherlands (D.K., S.V., D.T., K.J.); and the Department of Pediatrics, Intensive Care Unit, University of Alberta, Stollery Children's Hospital, Edmonton, Canada (G.G.G., J.H., A.J.).
authors.forename: Michael P
authors.initials: MP
authors.lastname: Casaer
authors.affiliation: From the Department of Cellular and Molecular Medicine, Clinical Division and Laboratory of Intensive Care Medicine, KU Leuven University Hospital, Leuven, Belgium (T.F., D.M., P.J.W., I.V., Y.D., D.V., L.D., M.P.C., J.H., G.V.B.); the Department of Pediatrics and Pediatric Surgery, Intensive Care, Erasmus-MC Sophia Children's Hospital, Rotterdam, the Netherlands (D.K., S.V., D.T., K.J.); and the Department of Pediatrics, Intensive Care Unit, University of Alberta, Stollery Children's Hospital, Edmonton, Canada (G.G.G., J.H., A.J.).
authors.forename: Gonzalo
authors.initials: G
authors.lastname: Garcia Guerra
authors.affiliation: From the Department of Cellular and Molecular Medicine, Clinical Division and Laboratory of Intensive Care Medicine, KU Leuven University Hospital, Leuven, Belgium (T.F., D.M., P.J.W., I.V., Y.D., D.V., L.D., M.P.C., J.H., G.V.B.); the Department of Pediatrics and Pediatric Surgery, Intensive Care, Erasmus-MC Sophia Children's Hospital, Rotterdam, the Netherlands (D.K., S.V., D.T., K.J.); and the Department of Pediatrics, Intensive Care Unit, University of Alberta, Stollery Children's Hospital, Edmonton, Canada (G.G.G., J.H., A.J.).
authors.forename: Jan
authors.initials: J
authors.lastname: Hanot
authors.affiliation: From the Department of Cellular and Molecular Medicine, Clinical Division and Laboratory of Intensive Care Medicine, KU Leuven University Hospital, Leuven, Belgium (T.F., D.M., P.J.W., I.V., Y.D., D.V., L.D., M.P.C., J.H., G.V.B.); the Department of Pediatrics and Pediatric Surgery, Intensive Care, Erasmus-MC Sophia Children's Hospital, Rotterdam, the Netherlands (D.K., S.V., D.T., K.J.); and the Department of Pediatrics, Intensive Care Unit, University of Alberta, Stollery Children's Hospital, Edmonton, Canada (G.G.G., J.H., A.J.).
authors.forename: Ari
authors.initials: A
authors.lastname: Joffe
authors.affiliation: From the Department of Cellular and Molecular Medicine, Clinical Division and Laboratory of Intensive Care Medicine, KU Leuven University Hospital, Leuven, Belgium (T.F., D.M., P.J.W., I.V., Y.D., D.V., L.D., M.P.C., J.H., G.V.B.); the Department of Pediatrics and Pediatric Surgery, Intensive Care, Erasmus-MC Sophia Children's Hospital, Rotterdam, the Netherlands (D.K., S.V., D.T., K.J.); and the Department of Pediatrics, Intensive Care Unit, University of Alberta, Stollery Children's Hospital, Edmonton, Canada (G.G.G., J.H., A.J.).
authors.forename: Dick
authors.initials: D
authors.lastname: Tibboel
authors.affiliation: From the Department of Cellular and Molecular Medicine, Clinical Division and Laboratory of Intensive Care Medicine, KU Leuven University Hospital, Leuven, Belgium (T.F., D.M., P.J.W., I.V., Y.D., D.V., L.D., M.P.C., J.H., G.V.B.); the Department of Pediatrics and Pediatric Surgery, Intensive Care, Erasmus-MC Sophia Children's Hospital, Rotterdam, the Netherlands (D.K., S.V., D.T., K.J.); and the Department of Pediatrics, Intensive Care Unit, University of Alberta, Stollery Children's Hospital, Edmonton, Canada (G.G.G., J.H., A.J.).
authors.forename: Koen
authors.initials: K
authors.lastname: Joosten
authors.affiliation: From the Department of Cellular and Molecular Medicine, Clinical Division and Laboratory of Intensive Care Medicine, KU Leuven University Hospital, Leuven, Belgium (T.F., D.M., P.J.W., I.V., Y.D., D.V., L.D., M.P.C., J.H., G.V.B.); the Department of Pediatrics and Pediatric Surgery, Intensive Care, Erasmus-MC Sophia Children's Hospital, Rotterdam, the Netherlands (D.K., S.V., D.T., K.J.); and the Department of Pediatrics, Intensive Care Unit, University of Alberta, Stollery Children's Hospital, Edmonton, Canada (G.G.G., J.H., A.J.).
authors.forename: Greet
authors.initials: G
authors.lastname: Van den Berghe
mesh_terms: D002648:Child; D002675:Child, Preschool; D016638:Critical Illness / Q000401:mortality / Q000628:therapy*; D004750:Enteral Nutrition; D005260:Female; D005440:Fluid Therapy; D006801:Humans; D007223:Infant; D007239:Infections / Q000453:epidemiology; D015278:Intensive Care Units, Pediatric; D053208:Kaplan-Meier Estimate; D007902:Length of Stay; D008297:Male; D010288:Parenteral Nutrition; D012121:Respiration, Artificial; D013997:Time Factors; D005723:gamma-Glutamyltransferase / Q000097:blood
chemical_list: D005723:gamma-Glutamyltransferase