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Parenteral and enteral nutrition in surgical critical care: Plasma metabolomics demonstrates divergent effects on nitrogen, fatty-acid, ribonucleotide, and oxidative metabolism

Parent, Brodie A. MD, MS; Seaton, Max MD; Djukovic, Danijel PhD; Gu, Haiwei PhD; Wheelock, Brittany; Navarro, Sandi L. PhD; Raftery, Daniel PhD; O’Keefe, Grant E. MD, MPH

Journal of Trauma and Acute Care Surgery: April 2017 - Volume 82 - Issue 4 - p 704–713
doi: 10.1097/TA.0000000000001381
AAST Plenary Papers
Editor's Choice

BACKGROUND: 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.

METHODS: 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.

RESULTS: 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).

CONCLUSION: 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.

LEVEL OF EVIDENCE: Therapeutic study, level III; prognostic study, level II.

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.

Submitted: August 31, 2016, Revised: October 24, 2016, Accepted: December 22, 2016, Published online: January 26, 2017.

This study was presented at the 75th annual meeting of the American Association for the Surgery of Trauma, September 13–16, 2016, in Waikoloa, Hawaii.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text, and links to the digital files are provided in the HTML text of this article on the journal’s Web site (

Address for reprints: Brodie A. Parent, MD, MS, Department of Surgery, University of Washington Medical Center, Harborview 325 9th Ave, Seattle, WA 98104; email:

© 2017 Lippincott Williams & Wilkins, Inc.