title: 24-Hour protein, arginine and citrulline metabolism in fed critically ill children - A stable isotope tracer study.
abstract: The reference method to study protein and arginine metabolism in critically ill children is measuring plasma amino acid appearances with stable isotopes during a short (4-8 h) time period and extrapolate results to 24-h. However, 24-h measurements may be variable due to critical illness related factors and a circadian rhythm could be present. Since only short duration stable isotope studies in critically ill children have been conducted before, the aim of this study was to investigate 24-h appearance of specific amino acids representing protein and arginine metabolism, with stable isotope techniques in continuously fed critically ill children.
  
  
  
  In eight critically ill children, admitted to the pediatric (n = 4) or cardiovascular (n = 4) intensive care unit, aged 0-10 years, receiving continuous (par)enteral nutrition with protein intake 1.0-3.7 g/kg/day, a 24-h stable isotope tracer protocol was carried out. L-[ring-2H5]-phenylalanine, L-[3,3-2H2]-tyrosine, L-[5,5,5-2H3]-leucine, L-[guanido-15N2]-arginine and L-[5-13C-3,3,4,4-2H4]-citrulline were infused intravenously and L-[15N]-phenylalanine and L-[1-13C]leucine enterally. Arterial blood was sampled every hour.
  
  
  
  Coefficients of variation, representing intra-individual variability, of the amino acid appearances of phenylalanine, tyrosine, leucine, arginine and citrulline were high, on average 14-19% for intravenous tracers and 23-26% for enteral tracers. No evident circadian rhythm was present. The pattern and overall 24-h level of whole body protein balance differed per individual.
  
  
  
  In continuously fed stable critically ill children, the amino acid appearances of phenylalanine, tyrosine, leucine, arginine and citrulline show high variability. This should be kept in mind when performing stable isotope studies in this population. There was no apparent circadian rhythm.
  
  
  
  NCT01511354 on clinicaltrials.gov.
authors.affiliation: Intensive Care and Department of Pediatric Surgery, Erasmus MC-Sophia Children's Hospital, Rotterdam, The Netherlands. Electronic address: carlijndebetue@gmail.com.
authors.forename: Carlijn T I
authors.initials: CTI
authors.lastname: de Betue
authors.affiliation: Department of Pediatric Cardiology & Critical Care Medicine, Arkansas Children's Hospital, Little Rock, AR, USA.
authors.forename: Xiomara C
authors.initials: XC
authors.lastname: Garcia Casal
authors.affiliation: Department of Pediatrics, Maastricht University Medical Center, Maastricht, The Netherlands.
authors.forename: Dick A
authors.initials: DA
authors.lastname: van Waardenburg
authors.affiliation: Department of Pediatric Cardiology & Critical Care Medicine, Arkansas Children's Hospital, Little Rock, AR, USA.
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Schexnayder
authors.affiliation: Department of Pediatrics, Erasmus MC-Sophia Children's Hospital, Rotterdam, The Netherlands.
authors.forename: Koen F M
authors.initials: KFM
authors.lastname: Joosten
authors.affiliation: Department of Geriatrics, Center of Translational Research on Aging and Longevity Department of Geriatrics, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
authors.forename: Nicolaas E P
authors.initials: NEP
authors.lastname: Deutz
authors.affiliation: Department of Geriatrics, Center of Translational Research on Aging and Longevity Department of Geriatrics, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
authors.forename: Marielle P K J
authors.initials: MPKJ
authors.lastname: Engelen
mesh_terms: D001120:Arginine / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism*; D002247:Carbon Isotopes / Q000097:blood; D002648:Child; D002675:Child, Preschool; D002940:Circadian Rhythm; D002956:Citrulline / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism*; D016638:Critical Illness / Q000628:therapy*; D004044:Dietary Proteins / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism*; D004750:Enteral Nutrition; D006801:Humans; D007223:Infant; D007362:Intensive Care Units; D007930:Leucine / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism; D010649:Phenylalanine / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism; D014443:Tyrosine / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism
chemical_list: D002247:Carbon Isotopes; D004044:Dietary Proteins; D002956:Citrulline; D014443:Tyrosine; D010649:Phenylalanine; D001120:Arginine; D007930:Leucine
keywords: 24-Hour pattern; Amino acid metabolism; Circadian rhythm; Critical illness; Pediatric; Protein metabolism