title: Parenteral and enteral nutrition in surgical critical care: Plasma metabolomics demonstrates divergent effects on nitrogen, fatty-acid, ribonucleotide, and oxidative metabolism.
abstract: Artificial nutrition support is central to the care of critically ill patients and is primarily provided enterally (EN). There are circumstances when parenteral nutrition (PN) is considered necessary. We are uncertain how each of these approaches confer clinical benefits beyond simply providing calories. We sought to better understand how each of these techniques influence metabolism in critically ill patients using a broad-based metabolomics approach. Metabolic responses to EN and PN may differ in ways that could help us understand how to optimize use of these therapies.
  
  
  
  We prospectively enrolled subjects over 7 months in 2015 at an urban, Level I trauma center. Subjects were included before starting either EN or PN during their inpatient admission. Plasma samples were obtained between 1 and 12 hours before initiation of artificial nutrition, and 3 and 7 days later. All samples were analyzed with liquid chromatography/mass spectrometry-based metabolomics. Differences in metabolite concentrations were assessed via principal component analyses and multiple linear regression.
  
  
  
  We enrolled 30 subjects. Among the critically ill subjects, 10 received EN and 10 received PN. In subjects receiving EN, amino acid and urea cycle metabolites (citrulline, p = 0.04; ornithine, p = 0.05) increased, as did ribonucleic acid metabolites (uridine, p = 0.04; cysteine, 0 = 0.05; oxypurinol, p = 0.04). Oxidative stress decreased over time (increased betaine, p = 0.05; decreased 4-pyridoxic acid, p = 0.04). In subjects receiving PN, amino acid concentrations increased over time (taurine, p = 0.04; phenylalanine, p = 0.05); omega 6 and omega 3 fatty acid concentrations decreased over time (p = 0.05 and 0.03, respectively).
  
  
  
  EN was associated with amino acid repletion, urea cycle upregulation, restoration of antioxidants, and increasing ribonucleic acid synthesis. Parenteral nutrition was associated with increased amino acid concentrations, but did not influence protein metabolism or antioxidant repletion. This suggests that parenteral amino acids are used less effectively than those given enterally. The biomarkers reported in this study may be useful in guiding nutrition therapy for critically ill patients.
  
  
  
  Therapeutic study, level III; prognostic study, level II.
authors.affiliation: From the Department of Surgery (B.A.P., M.S., D.D., B.W., G.E.O.) University of Washington Medical Center Harborview, Seattle Washington; Department of Surgery (M.S.), University of Maryland, Baltimore, Maryland; Mitochondria and Metabolism Center (H.G., D.R.), University of Washington, Seattle, Washington; Department of Epidemiology and Nutrition (S.L.N.), University of Washington, Seattle, Washington.
authors.forename: Brodie A
authors.initials: BA
authors.lastname: Parent
authors.forename: Max
authors.initials: M
authors.lastname: Seaton
authors.forename: Danijel
authors.initials: D
authors.lastname: Djukovic
authors.forename: Haiwei
authors.initials: H
authors.lastname: Gu
authors.forename: Brittany
authors.initials: B
authors.lastname: Wheelock
authors.forename: Sandi L
authors.initials: SL
authors.lastname: Navarro
authors.forename: Daniel
authors.initials: D
authors.lastname: Raftery
authors.forename: Grant E
authors.initials: GE
authors.lastname: O'Keefe
mesh_terms: D000328:Adult; D002853:Chromatography, Liquid; D003422:Critical Care; D004750:Enteral Nutrition / Q000379:methods*; D005227:Fatty Acids / Q000097:blood*; D006801:Humans; D013058:Mass Spectrometry; D055432:Metabolomics; D008875:Middle Aged; D009584:Nitrogen / Q000097:blood*; D018384:Oxidative Stress; D010288:Parenteral Nutrition / Q000379:methods*; D010949:Plasma / Q000378:metabolism*; D011446:Prospective Studies; D012265:Ribonucleotides / Q000097:blood*; D013514:Surgical Procedures, Operative; D014193:Trauma Centers
chemical_list: D005227:Fatty Acids; D012265:Ribonucleotides; D009584:Nitrogen