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

Phase 3

Completed

• Conditions: Hepatectomy
• Interventions: Drug: Penthotal; Drug: Propofol; Drug: Desflurane

• Registration Number: NCT00219856
• Lead Sponsor: Rennes University Hospital

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.

Study Timeline

• Study Start: 2004-08
• Study First Submitted: 2005-09-13
• Study First Submitted QC: 2005-09-13
• Study First Posted: 2005-09-22
• Primary Completion: 2006-03
• Study Completion: 2006-03
• Status Verified: 2012-06
• Last Update Submitted: 2012-06-25
• Last Update Posted: 2012-06-26

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 34

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

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
2	Desflurane	Anesthesic induction with intravenous penthotal and maintenance with inhaled desflurane.
2	Penthotal	Anesthesic induction with intravenous penthotal and maintenance with inhaled desflurane.
1	Propofol	Anesthesic induction and maintenance with intravenous propofol.

Primary Outcome Measures

Name	Time	Method
Plasma MDA levels	30 minutes after the end of hepatic clamping

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Surgical Intensive Care Unit - Rennes University Hospital; 🇫🇷 Rennes, France