Randomized Controlled Trial
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Nov 27, 2020; 12(11): 1098-1114
Published online Nov 27, 2020. doi: 10.4254/wjh.v12.i11.1098
Metalloproteinase expression after desflurane preconditioning in hepatectomies: A randomized clinical trial
Eleni Koraki, Ioannis Mantzoros, Christos Chatzakis, Anna Gkiouliava, Angeliki Cheva, Athina Lavrentieva, Freideriki Sifaki, Helena Argiriadou, Isaak Kesisoglou, Konstantinos Galanos-Demiris, Stefanos Bitsianis, Konstantinos Tsalis
Eleni Koraki, Anna Gkiouliava, Freideriki Sifaki, Department of Anaesthesiology, “G Papanikolaou” General Hospital, Thessaloniki 57010, Greece
Ioannis Mantzoros, Christos Chatzakis, Konstantinos Galanos-Demiris, Stefanos Bitsianis, Konstantinos Tsalis, Fourth Department of Surgery, Medical School, Aristotle University of Thessaloniki, Thessaloniki 57010, Greece
Angeliki Cheva, Department of Pathology, Medical School, Aristotle University of Thessaloniki, Thessaloniki 54636, Greece
Athina Lavrentieva, First Department of Intensive Care Unit, "G Papanikolaou" General Hospital, Thessaloniki 57010, Greece
Helena Argiriadou, Department of Anaesthesiology and Intensive Care Unit, Aristotle University of Thessaloniki, AHEPA University Hospital, Thessaloniki 54636, Greece
Isaak Kesisoglou, Third Department of Surgery, Aristotle University of Thessaloniki, AHEPA University Hospital, Thessaloniki 54636, Greece
Author contributions: Koraki E, Tsalis K, Kesisoglou I and Mantzoros I designed the research; Chatzakis C, Gkiouliava A, Cheva A, Lavrentieva A, Sifaki F and Argiriadou H analyzed and interpreted the data; Koraki E, Mantzoros I, Chatzakis C, Gkiouliava A, Galanos-Demiris K and Bitsianis S wrote the paper.
Institutional review board statement: The study was reviewed and approved by the Institutional Review Board of the General Hospital of Thessaloniki, Georgios Papanikolaou, No. 763/26.06.2016.
Clinical trial registration statement: The study is registered at clinicaltrials.gov. The registration identification number is NCT03848780.
Informed consent statement: All study participants, or their legal guardian, provided informed written consent prior to study enrollment.
Conflict-of-interest statement: The authors declare no conflicts of interest.
Data sharing statement: No additional data are available.
CONSORT 2010 statement: The authors have read the CONSORT 2010 Statement, and the manuscript was prepared and revised according to the CONSORT 2010 Statement.
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: Anna Gkiouliava, MD, Doctor, Research Fellow, Department of Anaesthesiology, “G Papanikolaou” General Hospital, Exochi, Thessaloniki, Greece, Thessaloniki 57010, Greece. annagkou@auth.gr
Received: July 21, 2020
Peer-review started: July 21, 2020
First decision: September 14, 2020
Revised: September 26, 2020
Accepted: October 12, 2020
Article in press: October 12, 2020
Published online: November 27, 2020
Processing time: 126 Days and 2.3 Hours
Abstract
BACKGROUND

Hepatectomy with inflow occlusion results in ischemia-reperfusion injury; however, pharmacological preconditioning can prevent such injury and optimize the postoperative recovery of hepatectomized patients. The normal inflammatory response after a hepatectomy involves increased expression of metalloproteinases, which may signal pathologic hepatic tissue reformation.

AIM

To investigate the effect of desflurane preconditioning on these inflammatory indices in patients with inflow occlusion undergoing hepatectomy.

METHODS

This is a single-center, prospective, randomized controlled trial conducted at the 4th Department of Surgery of the Medical School of Aristotle University of Thessaloniki, between August 2016 and December 2017. Forty-six patients were randomized to either the desflurane treatment group for pharmacological preconditioning (by replacement of propofol with desflurane, administered 30 min before induction of ischemia) or the control group for standard intravenous propofol. The primary endpoint of expression levels of matrix metalloproteinases and their inhibitors was determined preoperatively and at 30 min posthepatic reperfusion. The secondary endpoints of neutrophil infiltration, coagulation profile, activity of antithrombin III (AT III), protein C (PC), protein S and biochemical markers of liver function were determined for 5 d postoperatively and compared between the groups.

RESULTS

The desflurane treatment group showed significantly increased levels of tissue inhibitor of metalloproteinases 1 and 2, significantly decreased levels of matrix metalloproteinases 2 and 9, decreased neutrophil infiltration, and less profound changes in the coagulation profile.  During the 5-d postoperative period, all patients showed significantly decreased activity of AT III, PC and protein S (vs baseline values, P < 0.05). The activity of AT III and PC differed significantly between the two groups from postoperative day 1 to postoperative day 5 (P < 0.05), showing a moderate drop in activity of AT III and PC in the desflurane treatment group and a dramatic drop in the control group. Compared to the control group, the desflurane treatment group also had significantly lower international normalized ratio values on all postoperative days (P < 0.005) and lower serum glutamic oxaloacetic transaminase and serum glutamic pyruvic transaminase values on postoperative days 2 and 3 (P < 0.05).   Total length of stay was significantly less in the desflurane group (P = 0.009).

CONCLUSION

Desflurane preconditioning can lessen the inflammatory response related to ischemia-reperfusion injury and may shorten length of hospitalization.

Keywords: Desflurane; Preconditioning; Hepatectomy; Inflammation; Metalloproteinases; Reperfusion injury

Core Tip: Ischemia-reperfusion injury remains a leading cause of morbidity and mortality in hepatectomies. In our study, 46 patients were randomly and equally allocated to receive pharmacological preconditioning with desflurane (intervention group) or not (control group) to compare inflammatory indices between the two groups. We found significantly reduced levels of matrix metalloproteinases 2 and 9, increased levels of tissue inhibitor matrix metalloproteinases 1 and 2, and decreased neutrophil infiltration in the intervention group. Thus, hepatoprotective strategies may ameliorate the pathophysiologic effects of ischemia-reperfusion during liver surgery, with our study suggesting a novel promising strategy that may benefit patients postoperatively.