Effects of Propofol on Oxidative Stress and Liver Regeneration After Partial Hepatectomy

Prospective, Randomized, Simple Blind Study Comparing the Effects of an Anaesthesia With Propofol to an Anaesthesia With Desflurane on Oxydative Stress and Liver Function Recovery After Hepatectomy

Propofol is an anaesthetic agent that showed in vitro and in vivo anti oxidant properties. No data are available concerning the potential benefit of a total anaesthesia with propofol in partial hepatic surgery. Patients who undergo partial hepatic resection have frequent liver insufficiency that could be related in part to the oxidative stress induced by clamping the hepatic vessels during the surgical intervention. Our hypothesis is that propofol, by increasing liver resistance to this ischemia-reperfusion phenomenon, could improve the remaining liver function recovery, and therefore could reduce post surgical morbidity.

The aim of the study is to evaluate the anti oxidant effects of propofol compared to another widely used anaesthetic agent, inhaled desflurane, during and after partial hepatic resection with hepatic vessels clamping. The primary endpoint will be the level of malondialdehyde (a plasmatic marker of oxidative stress), 30 minutes after the end of hepatic clamping.

Study Overview

• Status: Completed
• Conditions: Hepatectomy
• Intervention / Treatment: Drug: Propofol; Drug: Penthotal; Drug: Desflurane

Detailed Description

Propofol is an anaesthetic agent that showed in vitro and in vivo anti oxidant properties. No data are available concerning the potential benefit of a total anaesthesia with propofol in partial hepatic surgery. Patients who undergo partial hepatic resection have frequent liver insufficiency that could be related in part to the oxidative stress induced by clamping the hepatic hilum during the surgical intervention. Our hypothesis is that propofol, by increasing liver resistance to ischemic-reperfusion injury, could improve the remaining liver function recovery, and therefore could reduce post surgical morbidity.

The aim of the study is to evaluate the anti oxidant effects of propofol compared to another widely used anaesthetic agent, inhaled desflurane, during and after partial hepatic resection with hepatic hilum clamping.

The primary endpoint will be the level of malondialdehyde (a plasmatic marker of oxidative stress), 30 minutes after the end of hepatic clamping.

The evolution over time of other markers of oxidative stress will be studied (glutathione, myeloperoxidase, nitric oxide), as well as functional and biological markers of liver regeneration.

• Study Type: Interventional
• Enrollment (Actual): 34
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • Rennes, France, 35033
    • Surgical Intensive Care Unit - Rennes University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients over 18
• Need for partial hepatic resection requiring heptic clamping
• Resection of 4 liver segments or less
• In case of cirrhosis, child A
• Written informed consent

Non-inclusion Criteria:

• Hemochromatosis
• chemotherapy in the previous week before inclusion
• Thrombosis of the portal vein or the hepatic artery
• Absence of contraception among fertil woman
• Concomitant treatment that could have potential interaction with propofol
• Concomitant treatment known to have antioxidant properties
• Inclusion in another study protocol using a medication incompatible with the present study
• Patient in which the follow up seems impossible

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1; Anesthesic induction and maintenance with intravenous propofol.	Drug: Propofol; Induction : intravenous propofol aiming a concentration of 4 to 8 µg/ml; Maintenance : intravenous propofol aiming a concentration of 3 to 6 µg/ml
Active Comparator: 2; Anesthesic induction with intravenous penthotal and maintenance with inhaled desflurane.	Drug: Penthotal; Intravenous penthotal at the dose of 3 to 5 mg/kg; Drug: Desflurane; Inhaled desflurane aiming an alveolar concentration of 4 to 6 per cent.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Plasma MDA levels	30 minutes after the end of hepatic clamping

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Kinetics of post surgical biological hepatic function recovery	Gamma gluatamyltransferase; ASAT; ALAT; Factor V; AlfagluthationeS-transferase	Days 1, 2, 5, 10
Kinetics of post surgical hepatic function recovery	Monoethylglycinexylidide (MEGX) test	Day 2
Other biological markers of oxidative stress	Glutathione; Myeloperoxidase; Nitric oxide	Days 1 and 2
Hemodynamics during and after surgery	Mean arterial pressure; Heart rate; Diuresis	Days 1 and 2
Surgery related complications	Liver insufficiency; Hepato renal syndrome; Local infections	10 days

Collaborators and Investigators

• Sponsor: Rennes University Hospital
• Collaborators: Ministry of Health, France
• Investigators: Study Director: Yannick Malledant, MD, Rennes University Hospital; Study Chair: Bruno Laviolle, MD, Rennes University Hospital; Principal Investigator: David Aguillon, MD, Rennes University Hospital

Study record dates

Study Major Dates

• Study Start: August 1, 2004
• Primary Completion (Actual): March 1, 2006
• Study Completion (Actual): March 1, 2006

Study Registration Dates

• First Submitted: September 13, 2005
• First Submitted That Met QC Criteria: September 13, 2005
• First Posted (Estimate): September 22, 2005

Study Record Updates

• Last Update Posted (Estimate): June 26, 2012
• Last Update Submitted That Met QC Criteria: June 25, 2012
• Last Verified: June 1, 2012

More Information

Terms related to this study

• Keywords: Oxidative stress; Propofol; Hepatectomy
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Central Nervous System Depressants; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Hypnotics and Sedatives; Anesthetics, Inhalation; Propofol; Desflurane
• Other Study ID Numbers: AFSSAPS 040366; PHRC/03-02 (Other Identifier: Rennes University Hospital); CIC0203/026