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Beneficial Effects of Early Enteral Nutrition After Major Rectal Surgery: A Possible Role for Conditionally Essential Amino Acids? Results of a Randomized Clinical Trial

van Barneveld, Kevin W. Y. MD1; Smeets, Boudewijn J. J. MD2; Heesakkers, Fanny F. B. M. MANP2; Bosmans, Joanna W. A. M. MD1; Luyer, Misha D. MD, PhD2; Wasowicz, Dareczka MD, PhD3; Bakker, Jaap A. PhD4,5; Roos, Arnout N. MD, PhD6; Rutten, Harm J. T. MD, PhD2,7; Bouvy, Nicole D. MD, PhD1; Boelens, Petra G. MD, PhD8

doi: 10.1097/CCM.0000000000001640
Online Clinical Investigations
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Objectives: To investigate direct postoperative outcome and plasma amino acid concentrations in a study comparing early enteral nutrition versus early parenteral nutrition after major rectal surgery. Previously, it was shown that a low plasma glutamine concentration represents poor prognosis in ICU patients.

Design: A preplanned substudy of a previous prospective, randomized, open-label, single-centre study, comparing early enteral nutrition versus early parenteral nutrition in patients at high risk of postoperative ileus after surgery for locally advanced or locally recurrent rectal cancer. Early enteral nutrition reduced postoperative ileus, anastomotic leakage, and hospital stay.

Setting: Tertiary referral centre for locally advanced and recurrent rectal cancer.

Patients: A total of 123 patients with locally advanced or recurrent rectal carcinoma requiring major rectal surgery.

Interventions: Patients were randomized (ALEA web-based external randomization) preoperatively into two groups: early enteral nutrition (early enteral nutrition, intervention) by nasojejunal tube (n = 61) or early parenteral nutrition (early parenteral nutrition, control) by jugular vein catheter (n = 62). Eight hours after the surgical procedure artificial nutrition was started in hemodynamically stable patients, stimulating oral intake in both groups. Blood samples were collected to measure plasma glutamine, citrulline, and arginine concentrations using a validated ultra performance liquid chromatography-tandem mass spectrometric method.

Measurements and Main Results: Baseline concentrations were comparable for both groups. Directly after rectal surgery, a decrease in plasma amino acids was observed. Plasma glutamine concentrations were higher in the parenteral group than in the enteral group on postoperative day 1 (p = 0.027) and day 5 (p = 0.008). Arginine concentrations were also significantly increased in the parenteral group at day 1 (p < 0.001) and day 5 (p = 0.001).

Conclusions: Lower plasma glutamine and arginine concentrations were measured in the enteral group, whereas a better clinical outcome was observed. We conclude that plasma amino acids do not provide a causal explanation for the observed beneficial effects of early enteral feeding after major rectal surgery.

1Department of Surgery, Research Institute for Nutrition, Toxicology and Metabolism, Maastricht University Medical Centre, Maastricht, The Netherlands.

2Department of Surgery, Catharina Hospital Eindhoven, Eindhoven, The Netherlands.

3Department of Surgery, St. Elisabeth Hospital Tilburg, Tilburg, The Netherlands.

4Department of Clinical Chemistry, Leiden University Medical Centre, Leiden, The Netherlands.

5Department of Clinical Genetics, Maastricht University Medical Centre, Maastricht, The Netherlands.

6Department of Intensive Care Medicine, Catharina Hospital Eindhoven, Eindhoven, The Netherlands.

7Department of Surgery, Research Institute for Growth and Development, Maastricht University Medical Centre, Maastricht, The Netherlands.

8Department of Surgery, Leiden University Medical Centre, Leiden, Maastricht, The Netherlands.

Supported, in part, by Department of General Surgery, Maastricht University Medical Centre. The original study was supported by an unconditional, nonrestrictive research grant by Nutricia Netherlands BV, Zoetermeer, The Netherlands.

Institutions of Drs. van Barneveld, Smeets, Luyer, and Boelens received funding from Nutricia Netherlands BV, Zoetermeer, the Netherlands. The remaining authors have disclosed that they do not have any potential conflicts of interest.

Address requests for reprints to: Boudewijn J. J. Smeets, MD, Department of Surgery, Catharina Hospital Eindhoven, Michelangelolaan 2, 5623 EJ Eindhoven, The Netherlands. E-mail: boudewijn.smeets@catharinaziekenhuis.nl

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