Randomized Clinical Trial
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Mar 27, 2019; 11(3): 305-317
Published online Mar 27, 2019. doi: 10.4254/wjh.v11.i3.305
Preoperative immunonutrition in patients undergoing liver resection: A prospective randomized trial
Kylie Russell, Han-Guang Zhang, Lyn K Gillanders, Adam SJR Bartlett, Helena L Fisk, Philip C Calder, Peter J Swan, Lindsay D Plank
Kylie Russell, Lyn K Gillanders, Nutrition Services, Auckland City Hospital, Auckland 1023, New Zealand
Han-Guang Zhang, Adam SJR Bartlett, Peter J Swan, Lindsay D Plank, Department of Surgery, University of Auckland, Auckland 1023, New Zealand
Adam SJR Bartlett, New Zealand Liver Transplant Unit, Auckland City Hospital, Auckland 1023, New Zealand
Helena L Fisk, Philip C Calder, Human Development and Health, Faculty of Medicine, University of Southampton, Southampton SO171BJ, United Kingdom
Philip C Calder, NIHR Southampton Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust and University of Southampton, Southampton SO166YD, United Kingdom
Author contributions: Russell K, Zhang HG, Gillanders LK, Bartlett AJSR and Plank LD designed the study; Russell K, Zhang HG, Fisk HL, and Plank LD acquired the data; Russell K, Zhang H-G and Plank LD analysed and interpreted the data; Gillanders LK, Bartlett AJSR, Calder PC and Swan PJ contributed to interpretation of the results; Russell K and Plank LD wrote the manuscript; Gillanders LK, Bartlett AJSR, Fisk HL, Calder PC and Swan PJ provided critical revisions of the manuscript; all authors read and approved the final version of the manuscript.
Supported by: Australasian Society for Parenteral and Enteral Nutrition Research Grant and A+ Trust Small Project Grant, No. 5576.
Institutional review board statement: The study was reviewed and approved by the New Zealand Health and Disability Ethics Northern A Committee (NTX/12/06/056).
Clinical trial registration statement: This study is registered with the Australian and New Zealand Clinical Trials Registry (ACTRN12612001151820).
Informed consent statement: All study participants provided written informed consent prior to study enrolment.
Conflict-of-interest statement: None of the authors has any conflicts of interest related to this study.
Data sharing statement: No additional data are available.
CONSORT 2010 statement: The authors have read the CONSORT 2010 Statement and the manuscript was prepared according to the CONSORT 2010 Statement.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Lindsay D Plank, DPhil, Associate Professor, Department of Surgery, University of Auckland, 2 Park Road, Auckland 1023, New Zealand. l.plank@auckland.ac.nz
Telephone: +64-9-9236949 Fax: +64-9-3779656
Received: October 25, 2018
Peer-review started: October 26, 2018
First decision: December 19, 2018
Revised: February 22, 2019
Accepted: March 16, 2019
Article in press: March 16, 2019
Published online: March 27, 2019
Processing time: 153 Days and 8.6 Hours
ARTICLE HIGHLIGHTS
Research background

Immunonutrients provided pre- and perioperatively to patients undergoing major gastrointestinal surgery have been shown in a number of studies to reduce postoperative morbidity. Nutritional supplementation enriched in n-3 long-chain fatty acids and arginine has been used in the majority of these studies and these nutrients are thought to modulate the inflammatory and immune responses to surgery leading to improved clinical outcome.

Research motivation

We were motivated to design and implement a randomized trial of immunonutrition in patients undergoing liver resection given that only one such prospective trial had previously been reported. That trial had a high dropout rate and we considered further work was needed.

Research objectives

The main objective of this study was to evaluate the effect of preoperative supplemental immunonutrition, enriched in n-3 fatty acids and arginine, on postoperative inflammatory and immune markers. A secondary objective was to examine effects on clinical outcome.

Research methods

Patients scheduled for non-laparoscopic elective hepatic resection for primary or secondary liver cancer were randomized in an assessor-blinded prospective trial to preoperative immunonutrition (IMPACT Advanced Recovery®, 1020 kcal/d) for 5 consecutive days or to standard care. Blood samples were obtained at recruitment, on the day prior to surgery and on postoperative day (POD) 1, 3, 5 and 7 for measurement of plasma fatty acids and markers of inflammation and immune status. Patients were monitored for 30 POD for infectious and other complications.

Research results

Immune markers did not differ between the groups. Postoperative inflammatory response, as assessed by interleukin-6 concentrations, was more pronounced in the immunonutrition group. Ten patients in the immunonutrition group and 4 in the standard care group developed infectious complications. Major postoperative complications were more common in the immunonutrition group.

Research conclusions

In this study, provision of a preoperative immunonutritional supplement was not associated with post-surgery suppression of inflammation nor with improved clinical outcomes. The higher incidence of major complications in the immunonutrition group may have contributed to these findings.

Research perspectives

Since completion of this study a similar preoperative immunonutrition regime was reported in a randomized trial demonstrating reduced postoperative inflammatory response and improved clinical outcome with immunonutrition. The majority of patients in that study had a relatively rare indication for liver resection. Future efforts should be directed at double-blind trials of immunonutritional formulae, in patients undergoing major liver resections for commonly seen indications, that are adequately powered to assess postoperative infectious complications.