Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Trials
Published in: Trials 1/2015

Open Access 01-12-2015 | Study protocol

The effects of stimulation of the autonomic nervous system via perioperative nutrition on postoperative ileus and anastomotic leakage following colorectal surgery (SANICS II trial): a study protocol for a double-blind randomized controlled trial

Authors: Emmeline G Peters, Boudewijn JJ Smeets, Marloes Dekkers, Marc D Buise, Wouter J de Jonge, Gerrit D Slooter, Tammo S de Vries Reilingh, Johannes A Wegdam, Grard AP Nieuwenhuijzen, Harm JT Rutten, Ignace HJT de Hingh, Mickael Hiligsmann, Wim A Buurman, Misha DP Luyer

Published in: Trials | Issue 1/2015

Login to get access

Abstract

Background

Postoperative ileus and anastomotic leakage are important complications following colorectal surgery associated with short-term morbidity and mortality. Previous experimental and preclinical studies have shown that a short intervention with enriched enteral nutrition dampens inflammation via stimulation of the autonomic nervous system and thereby reduces postoperative ileus. Furthermore, early administration of enteral nutrition reduced anastomotic leakage. This study will investigate the effect of nutritional stimulation of the autonomic nervous system just before, during and early after colorectal surgery on inflammation, postoperative ileus and anastomotic leakage.

Methods/Design

This multicenter, prospective, double-blind, randomized controlled trial will include 280 patients undergoing colorectal surgery. All patients will receive a selfmigrating nasojejunal tube that will be connected to a specially designed blinded tubing system. Patients will be allocated either to the intervention group, receiving perioperative nutrition, or to the control group, receiving no nutrition. The primary endpoint is postoperative ileus. Secondary endpoints include anastomotic leakage, local and systemic inflammation, (aspiration) pneumonia, surgical complications classified according to Clavien-Dindo, quality of life, gut barrier integrity and time until functional recovery. Furthermore, a cost-effectiveness analysis will be performed.

Discussion

Activation of the autonomic nervous system via perioperative enteral feeding is expected to dampen the local and systemic inflammatory response. Consequently, postoperative ileus will be reduced as well as anastomotic leakage. The present study is the first to investigate the effects of enriched nutrition given shortly before, during and after surgery in a clinical setting.

Trial registration

ClinicalTrials.gov: NCT02175979 - date of registration: 25 June 2014.
Dutch Trial Registry: NTR4670 - date of registration: 1 August 2014.
Literature
1.
Spanjersberg WR, Reurings J, Keus F, van Laarhoven CJ. Fast track surgery versus conventional recovery strategies for colorectal surgery. Cochrane Database Syst Rev. 2011;2, CD007635.
2.
Zhuang CL, Ye XZ, Zhang XD, Chen BC, Yu Z. Enhanced recovery after surgery programs versus traditional care for colorectal surgery: a meta-analysis of randomized controlled trials. Dis Colon Rectum. 2013;56(5):667–78.CrossRefPubMed
3.
Kalff JC, Schraut WH, Simmons RL, Bauer AJ. Surgical manipulation of the gut elicits an intestinal muscularis inflammatory response resulting in postsurgical ileus. Ann Surg. 1998;228(5):652–63.CrossRefPubMedPubMedCentral
4.
Boeckxstaens GE, de Jonge WJ. Neuroimmune mechanisms in postoperative ileus. Gut. 2009;58(9):1300–11.CrossRefPubMed
5.
Luyer MD, Buurman WA, Hadfoune M, Jacobs JA, Konstantinov SR, Dejong CH, et al. Pretreatment with high-fat enteral nutrition reduces endotoxin and tumor necrosis factor-alpha and preserves gut barrier function early after hemorrhagic shock. Shock. 2004;21(1):65–71.CrossRefPubMed
6.
Luyer MD, Buurman WA, Hadfoune M, Jacobs JA, Dejong CH, Greve JW. High-fat enteral nutrition reduces endotoxin, tumor necrosis factor-alpha and gut permeability in bile duct-ligated rats subjected to hemorrhagic shock. J Hepatol. 2004;41(3):377–83.CrossRefPubMed
7.
Lubbers T, de Haan JJ, Luyer MD, Verbaeys I, Hadfoune M, Dejong CH, et al. Cholecystokinin/Cholecystokinin-1 receptor-mediated peripheral activation of the afferent vagus by enteral nutrients attenuates inflammation in rats. Ann Surg. 2010;252(2):376–82.CrossRefPubMed
8.
Luyer MD, Greve JW, Hadfoune M, Jacobs JA, Dejong CH, Buurman WA. Nutritional stimulation of cholecystokinin receptors inhibits inflammation via the vagus nerve. J Exp Med. 2005;202(8):1023–9.CrossRefPubMedPubMedCentral
9.
Lubbers T, Kox M, de Haan JJ, Greve JW, Pompe JC, Ramakers BP, et al. Continuous administration of enteral lipid- and protein-rich nutrition limits inflammation in a human endotoxemia model. Crit Care Med. 2013;41(5):1258–65.CrossRefPubMed
10.
de Jonge WJ, van der Zanden EP, The FO, Bijlsma MF, van Westerloo DJ, Bennink RJ, et al. Stimulation of the vagus nerve attenuates macrophage activation by activating the Jak2-STAT3 signaling pathway. Nat Immunol. 2005;6(8):844–51.CrossRefPubMed
11.
Wang H, Yu M, Ochani M, Amella CA, Tanovic M, Susarla S, et al. Nicotinic acetylcholine receptor alpha7 subunit is an essential regulator of inflammation. Nature. 2003;421(6921):384–8.CrossRefPubMed
12.
Boelens PG, Heesakkers FF, Luyer MD, van Barneveld KW, de Hingh IH, Nieuwenhuijzen GA, et al. Reduction of postoperative ileus by early enteral nutrition in patients undergoing major rectal surgery: prospective, randomized, controlled trial. Ann Surg. 2014;259(4):649–55.CrossRefPubMed
13.
van den Heijkant TC, Costes LMM, van der Lee DGC, Aerts B, Osinga-de Jong M, Rutten HJT, et al. Randomized clinical trial on the effect of gum chewing on postoperative ileus and inflammation in colorectal surgery. Br J Surg. 2014. doi: 10.1002/bjs.9691.
14.
Mirnezami A, Mirnezami R, Chandrakumaran K, Sasapu K, Sagar P, Finan P. Increased local recurrence and reduced survival from colorectal cancer following anastomotic leak: systematic review and meta-analysis. Ann Surg. 2011;253(5):890–9.CrossRefPubMed
15.
Vather R, Trivedi S, Bissett I. Defining postoperative ileus: results of a systematic review and global survey. J Gastrointest Surg. 2013;17(5):962–72.CrossRefPubMed
16.
Darwiche G, Bjorgell O, Thorsson O, Almer LO. Correlation between simultaneous scintigraphic and ultrasonographic measurement of gastric emptying in patients with type 1 diabetes mellitus. J Ultrasound Med. 2003;22(5):459–66.CrossRefPubMed
17.
Dindo D, Demartines N, Clavien PA. Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg. 2004;240(2):205–13.CrossRefPubMedPubMedCentral
18.
Ashraf SQ, Burns EM, Jani A, Altman S, Young JD, Cunningham C, et al. The economic impact of anastomotic leakage after anterior resections in English NHS hospitals: are we adequately remunerating them? Colorectal Dis. 2013;15(4):e190–8.CrossRefPubMed
19.
Iyer S, Saunders WB, Stemkowski S. Economic burden of postoperative ileus associated with colectomy in the United States. J Manag Care Pharm. 2009;15(6):485–94.PubMed
20.
Gooiker GA, Dekker JW, Bastiaannet E, van der Geest LG, Merkus JW, van de Velde CJ, et al. Risk factors for excess mortality in the first year after curative surgery for colorectal cancer. Ann Surg Oncol. 2012;19(8):2428–34.CrossRefPubMedPubMedCentral
21.
Story SK, Chamberlain RS. A comprehensive review of evidence-based strategies to prevent and treat postoperative ileus. Dig Surg. 2009;26(4):265–75.CrossRefPubMed
22.
Ishimura K, Moroguchi A, Okano K, Maeba T, Maeta H. Local expression of tumor necrosis factor-alpha and interleukin-10 on wound healing of intestinal anastomosis during endotoxemia in mice. J Surg Res. 2002;108(1):91–7.CrossRefPubMed
23.
Cerantola Y, Hubner M, Grass F, Demartines N, Schafer M. Immunonutrition in gastrointestinal surgery. Br J Surg. 2011;98(1):37–48.CrossRefPubMed
Metadata
Title
The effects of stimulation of the autonomic nervous system via perioperative nutrition on postoperative ileus and anastomotic leakage following colorectal surgery (SANICS II trial): a study protocol for a double-blind randomized controlled trial
Authors
Emmeline G Peters
Boudewijn JJ Smeets
Marloes Dekkers
Marc D Buise
Wouter J de Jonge
Gerrit D Slooter
Tammo S de Vries Reilingh
Johannes A Wegdam
Grard AP Nieuwenhuijzen
Harm JT Rutten
Ignace HJT de Hingh
Mickael Hiligsmann
Wim A Buurman
Misha DP Luyer
Publication date
01-12-2015
Publisher
BioMed Central
Published in
Trials / Issue 1/2015
Electronic ISSN: 1745-6215
DOI
https://doi.org/10.1186/s13063-014-0532-x

Other articles of this Issue 1/2015

Trials 1/2015 Go to the issue

Study protocol

Reduced patient restrictions following total hip arthroplasty: study protocol for a randomized controlled trial

Research

Analysis of cervical resistance during continuous controllable balloon dilatation: controlled clinical and experimental study

Study protocol

The Italian Diabetes and Exercise Study 2 (IDES-2): a long-term behavioral intervention for adoption and maintenance of a physically active lifestyle

Study protocol

Using mobile technology to deliver a cognitive behaviour therapy-informed intervention in early psychosis (Actissist): study protocol for a randomised controlled trial

Study protocol

An internet-based adolescent depression preventive intervention: study protocol for a randomized control trial

Study protocol

Derivation and validation phase for the development of clinical prediction rules for rehabilitation in chronic nonspecific low back pain patients: study protocol for a randomized controlled trial