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

Abstract

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.

Figure 1

Principal component analysis of plasma samples on day 0, day 3 and day 7 for a) subjects started on enteral nutrition and b) subjects started on parenteral nutrition.ϕ ϕ Each data point represents an individual plasma sample. Points which are close together represent samples with similar metabolic phenotypes; points which are far away have dissimilar metabolic phenotypes. The large symbols represent the mean values of the sample scores for a given group.

Figure 2

Plasma metabolome heat-maps for: I) subjects on enteral nutrition over time, demonstrating a) increasing amino acid and urea cycle metabolites, and b) increasing RNA synthetic products; II) subjects on parenteral nutrition over time, demonstrating c) decreasing urea cycle metabolites, and d) decreasing essential fatty acids.ϕ ϕ Generated using mass-spectrometry based metabolomics. Due to unmeasurably low levels of relevant metabolites, one sample was omitted from parts a) and b), and two samples were omitted from parts c) and d).

Figure 2

Plasma metabolome heat-maps for: I) subjects on enteral nutrition over time, demonstrating a) increasing amino acid and urea cycle metabolites, and b) increasing RNA synthetic products; II) subjects on parenteral nutrition over time, demonstrating c) decreasing urea cycle metabolites, and d) decreasing essential fatty acids.ϕ ϕ Generated using mass-spectrometry based metabolomics. Due to unmeasurably low levels of relevant metabolites, one sample was omitted from parts a) and b), and two samples were omitted from parts c) and d).

Figure 3

Plasma metabolomics for subjects on enteral nutrition over time, demonstrating a) increasing amino acids, b) increasing urea cycle metabolites, c) increasing RNA synthetic metabolites, and d) restoration of antioxidant balance.ϕ ϕ Generated using mass-spectrometry based metabolomics.

Figure 3

Plasma metabolomics for subjects on enteral nutrition over time, demonstrating a) increasing amino acids, b) increasing urea cycle metabolites, c) increasing RNA synthetic metabolites, and d) restoration of antioxidant balance.ϕ ϕ Generated using mass-spectrometry based metabolomics.

Figure 4

Plasma metabolomics for subjects on enteral nutrition over time, demonstrating a) increasing amino acids, b) low levels of urea cycle metabolites, and c) decreasing essential omega fatty-acids and increased endogenous fatty-acid transport (carnitine).ϕ ϕ Generated using mass-spectrometry based metabolomics.

Figure 4

Plasma metabolomics for subjects on enteral nutrition over time, demonstrating a) increasing amino acids, b) low levels of urea cycle metabolites, and c) decreasing essential omega fatty-acids and increased endogenous fatty-acid transport (carnitine).ϕ ϕ Generated using mass-spectrometry based metabolomics.