Desflurane Preconditioning in Hepatectomies

NCT03848780 | Completed

• 1 other identifier: 3779
• Study Type: interventional
• Target: 46
• Locations: 0 countries
• Sites: N/A

Brief Summary

Hepatectomies are considered as operations of high bleeding risk. The history of massive hemorrhage in liver surgery led to the emergence of techniques to control excessive blood loss. These techniques temporarily occlude the blood vessels that supply liver (the Pringle Maneuver) limiting subsequent losses. However, this leads to the ischemia - reperfusion injury impairing liver function. Research points to methods targeting on tempering reperfusion pathophysiology. Volatile anesthetics have been used for pharmacological preconditioning and proved to protect against organ damage. The aim of this study was to investigate the potential beneficial effect of desflurane on ischemia-reperfusion injury of the liver. Patients presenting for elective hepatectomy were randomized equally into two groups. The Control Group received no pharmacological preconditioning and the Desflurane Group received pharmacological preconditioning with Desflurane before induction of ischemia.

Conditions

Ischemia Reperfusion Injury

Keywords

preconditioning; hepatectomy; ischemia reperfusion injury

Outcome Measures

Primary Outcomes (2)

• Matrix Metalloproteinases (MMPs) 2 and 9 level

  The levels of Matrix Metalloproteinase 2 and Matrix Metalloproteinase 9 as evaluated by the relative gene expression using RT-PCR. The comparative CT method also referred to as the 2-ΔΔCT method was used to calculate the fold change and then convert it to percentage. Their presence has been linked to hepatic cellular injury so increased levels represent worse injury.

  Sample 1: At surgery, before initiation of the procedure , Sample 2: Thirty minutes after reperfusion

• Tissue Inhibitor Metalloproteinase (TIMPs) 1and 2

  The levels of Tissue Inhibitor Metalloproteinase 1 and Tissue Inhibitor Metalloproteinase 2 as evaluated by the relative gene expression using RT-PCR. The comparative CT method also referred to as the 2-ΔΔCT method was used to calculate the fold change and then convert it to percentage. Their inhibitory effect on Matrix Metalloproteinases has been associated with a limitation of cellular injury. Thus, the higher the levels of Tissue Inhibitor Metalloproteinases the greater their protective activity.

  Sample 1: At surgery, before initiation of the procedure , Sample 2: Thirty minutes after reperfusion

Secondary Outcomes (1)

• Histological findings of hepatic parenchyma

  Sample 1: Upon surgical dissection of the liver, before inflow occlusion, Sample: thirty minutes after reperfusion

Study Arms (2)

Desflurane Group

EXPERIMENTAL

Thirty minutes before initiation of ischemia the surgeon was instructed to notify the anesthesiologist. At this single time point, propofol infusion was stopped and substituted with the volatile anesthetic desflurane to achieve a Minimum Alveolar Concentration of 1. The procedure included a 5-minute induction of desflurane, a 20-minute preconditioning and a 5-minute washout period when propofol was reintroduced and desflurane stopped.

Drug: Desflurane

Control Group

NO INTERVENTION

No pharmacological preconditioning was implemented

Interventions

Desflurane DRUG

Desflurane Group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• hepatectomy of at least two segments

You may not qualify if:

• Hepatitis B, C or HIV infection
• liver cirrhosis
• autoimmune disease, inflammatory bowel disease
• pregnancy
• prior additional ablation therapies (cryosurgery or radiofrequency)
• liver resections without inflow occlusion

Sponsors & Collaborators

• Aristotle University Of Thessaloniki: lead

Related Publications (4)

• Rosen HR, Martin P, Goss J, Donovan J, Melinek J, Rudich S, Imagawa DK, Kinkhabwala M, Seu P, Busuttil RW, Shackleton CR. Significance of early aminotransferase elevation after liver transplantation. Transplantation. 1998 Jan 15;65(1):68-72. doi: 10.1097/00007890-199801150-00013.

  PMID: 9448146 BACKGROUND

• Kimura F, Shimizu H, Yoshidome H, Ohtsuka M, Kato A, Yoshitomi H, Nozawa S, Furukawa K, Mitsuhashi N, Sawada S, Takeuchi D, Ambiru S, Miyazaki M. Circulating cytokines, chemokines, and stress hormones are increased in patients with organ dysfunction following liver resection. J Surg Res. 2006 Jun 15;133(2):102-12. doi: 10.1016/j.jss.2005.10.025. Epub 2006 Jan 4.

  PMID: 16386757 BACKGROUND

• Boros P, Bromberg JS. New cellular and molecular immune pathways in ischemia/reperfusion injury. Am J Transplant. 2006 Apr;6(4):652-8. doi: 10.1111/j.1600-6143.2005.01228.x.

  PMID: 16539620 BACKGROUND

• Beck-Schimmer B, Breitenstein S, Urech S, De Conno E, Wittlinger M, Puhan M, Jochum W, Spahn DR, Graf R, Clavien PA. A randomized controlled trial on pharmacological preconditioning in liver surgery using a volatile anesthetic. Ann Surg. 2008 Dec;248(6):909-18. doi: 10.1097/SLA.0b013e31818f3dda.

  PMID: 19092335 BACKGROUND

MeSH Terms

Conditions

Reperfusion Injury

Interventions

Desflurane

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases; Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Ethyl Ethers; Ethers; Organic Chemicals; Methyl Ethers; Hydrocarbons, Fluorinated; Hydrocarbons, Halogenated; Hydrocarbons

Study Officials

• Eleni Koraki, Dr

  Aristotle University Of Thessaloniki

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal investigator, Anesthesiologist

Study Record Dates

• First Submitted: January 29, 2019
• First Posted: February 21, 2019
• Study Start: April 1, 2016
• Primary Completion: June 30, 2018
• Study Completion: June 30, 2018
• Last Updated: February 21, 2019

Record last verified: 2019-02

Data Sharing

• IPD Sharing: Will not share