Basic Study
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Pathophysiol. Jan 22, 2021; 12(1): 1-13
Published online Jan 22, 2021. doi: 10.4291/wjgp.v12.i1.1
Influence of anastomoses on intestine ischemia and cefuroxime concentrations: Evaluated in the ileum and colon in a porcine model
Pelle Hanberg, Mats Bue, Maja Thomassen, Uffe Schou Løve, Josephine Olsen Kipp, Christina Harlev, Elisabeth Petersen, Kjeld Søballe, Maiken Stilling
Pelle Hanberg, Department of Orthopaedic Surgery, Horsens Regional Hospital, Horsens 8700, Denmark
Pelle Hanberg, Mats Bue, Maja Thomassen, Josephine Olsen Kipp, Christina Harlev, Elisabeth Petersen, Kjeld Søballe, Maiken Stilling, Aarhus Microdialysis Research Group, Orthopaedic Research Unit, Aarhus University Hospital, Aarhus N 8200, Denmark
Pelle Hanberg, Mats Bue, Kjeld Søballe, Maiken Stilling, Department of Clinical Medicine, Aarhus University, Aarhus N 8200, Denmark
Mats Bue, Kjeld Søballe, Maiken Stilling, Department of Orthopaedic Surgery, Aarhus University Hospital, Aarhus N 8200, Denmark
Uffe Schou Løve, Department of Surgery, Viborg Regional Hospital, Viborg 8800, Denmark
Author contributions: Hanberg P, Bue M, Thomassen M, Løve US, Søballe K and Stilling M contributed study conception design; Hanberg P, Bue M, Thomassen M, Kipp JO, Harlev C and Petersen E contributed data acquisition; Hanberg P contributed data analysis and interpretation, and drafted the article; Hanberg P, Bue M, Thomassen M, Løve US, Kipp JO, Harlev C, Petersen E, Søballe K and Stilling M contributed critical revision; all authors have read and approved the final manuscript.
Institutional review board statement: The study was reviewed and approved by the Danish National Committee and the Animal Experiments Inspectorate.
Institutional animal care and use committee statement: The study was carried out according to existing laws and approved by the Danish Animal Experiments Inspectorate (license No.: 2017/15-0201-01184). All appropriate measures were taken to minimize animal pain and discomfort.
Conflict-of-interest statement: No conflict of interest.
Data sharing statement: Technical appendix, statistical code, and dataset available from the corresponding author at pellehanberg@clin.au.dk.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (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: Pelle Hanberg, MD, Department of Orthopaedic Surgery, Horsens Regional Hospital, Sundvej 30, Horsens 8700, Denmark. pellehanberg@clin.au.dk
Received: October 26, 2020
Peer-review started: October 26, 2020
First decision: November 20, 2020
Revised: November 30, 2020
Accepted: December 8, 2020
Article in press: December 8, 2020
Published online: January 22, 2021
Processing time: 86 Days and 23.9 Hours
Abstract
BACKGROUND

Anastomotic leakage is a serious complication following gastrointestinal surgery and is associated with increased morbidity and mortality. The incidence of anastomotic leakage is determined by anatomy and is reported to be between 4%-33% for colon anastomosis and 1%-3% for small intestine anastomosis. The etiology of anastomotic leakage of the intestine has been divided into three main factors: healing disturbances, communication between intra- and extra-luminal compartments, and infection. All three factors interact, and one factor will inevitably lead to the other two factors resulting in tissue ischemia, tissue necrosis, and anastomotic leakage.

AIM

To evaluate ischemic metabolites and cefuroxime concentrations in both anastomosis and non-anastomosis ileum and colon in a porcine model.

METHODS

Eight healthy female pigs (Danish Landrace breed, weight 58-62 kg) were included in this study. Microdialysis catheters were placed for sampling of ischemic metabolites (glucose, lactate, glycerol, and pyruvate) and cefuroxime concentrations in both anastomosis and non-anastomosis ileum and colon. Cefuroxime 1.5 g was administered as an intravenous infusion over 15 min. Subsequently, dialysates and blood samples were collected over 8 h and the ischemic metabolites and cefuroxime concentrations were quantified in all samples. The concentrations of glucose, lactate, glycerol and pyruvate were determined using the CMA 600 Microdialysis Analyzer with Reagent Set A (M Dialysis AB, Sweden), and the concentrations of cefuroxime and meropenem were quantified using a validated ultra-high-performance liquid chromatography assay.

RESULTS

Only the colon anastomosis induced mean ischemic lactate/pyruvate ratios above 25 (ischemic cut-off) throughout the entire sampling interval, and simultaneously decreased glucose concentrations. The mean time for which cefuroxime concentrations were maintained above the clinical breakpoint minimal inhibitory concentration for Escherichia coli (8 µg/mL) ranged between 116-128 min across all the investigated compartments, and was similar between the anastomosis and non-anastomosis ileum and colon. For all pigs and in all the investigated compartments, a cefuroxime concentration of 8 µg/mL was reached within 10 min after administration. When comparing the pharmacokinetic parameters between the anastomosis and non-anastomosis sites for both ileum and colon, only colon Tmax and half-life differed between anastomosis and non-anastomosis (P < 0.03). Incomplete tissue penetrations were found in all tissues except for the non-anastomosis colon.

CONCLUSION

Administering 1.5 g cefuroxime 10 min prior to intestine surgery seems sufficient, and effective concentrations are sustained for approximately 2 h. Only colon anastomosis was locally vulnerable to ischemia.

Keywords: Anastomosis; Cefuroxime; Colon; Ileum; Ischemic metabolites; Microdialysis

Core Tip: We found that only colon anastomosis was locally vulnerable to ischemia but reached similar cefuroxime concentrations to those in the remaining investigated intestine compartments. Our study suggests that administering 1.5 g cefuroxime 10 min prior to intestine surgery is sufficient, and that effective concentrations are sustained for approximately 2 h. This is the first study to investigate the influence of anastomoses on ileum and colon ischemic metabolites and cefuroxime concentrations in a simultaneous paired design.