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

NCT ID: NCT00219856

Last Updated: 2012-06-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 34 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-08-31
• Study Completion Date: 2006-03-31

Brief Summary

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.

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.

Conditions

Hepatectomy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

1

Anesthesic induction and maintenance with intravenous propofol.

Group Type: EXPERIMENTAL

Propofol

Intervention Type: DRUG

• Induction : intravenous propofol aiming a concentration of 4 to 8 µg/ml
• Maintenance : intravenous propofol aiming a concentration of 3 to 6 µg/ml

2

Anesthesic induction with intravenous penthotal and maintenance with inhaled desflurane.

Group Type: ACTIVE_COMPARATOR

Penthotal

Intervention Type: DRUG

Intravenous penthotal at the dose of 3 to 5 mg/kg

Desflurane

Intervention Type: DRUG

Inhaled desflurane aiming an alveolar concentration of 4 to 6 per cent.

Interventions

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

Intervention Type: DRUG

Penthotal

Intravenous penthotal at the dose of 3 to 5 mg/kg

Intervention Type: DRUG

Desflurane

Inhaled desflurane aiming an alveolar concentration of 4 to 6 per cent.

Intervention Type: DRUG

Eligibility Criteria

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

• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Ministry of Health, France

OTHER_GOV

Sponsor Role: collaborator

Rennes University Hospital

OTHER

Sponsor Role: lead

Responsible Party

Rennes University Hospital

Principal Investigators

David Aguillon, MD

Role: PRINCIPAL_INVESTIGATOR

Rennes University Hospital

Yannick Malledant, MD

Role: STUDY_DIRECTOR

Rennes University Hospital

Bruno Laviolle, MD

Role: STUDY_CHAIR

Rennes University Hospital

Locations

Surgical Intensive Care Unit - Rennes University Hospital

Rennes, , France

Countries

France

Other Identifiers

PHRC/03-02

Identifier Type: OTHER

Identifier Source: secondary_id

CIC0203/026

Identifier Type: -

Identifier Source: secondary_id

AFSSAPS 040366

Identifier Type: -

Identifier Source: org_study_id