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

Hepatectomy Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00219856
• Other study ID #: AFSSAPS 040366
• Secondary ID: PHRC/03-02CIC020
• Status: Completed
• Phase: Phase 3
• First received: September 13, 2005
• Last updated: June 25, 2012
• Start date: August 2004
• Est. completion date: March 2006

Study information

• Verified date: June 2012
• Source: Rennes University Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 34
• Est. completion date: March 2006
• Est. primary completion date: March 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Subject), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hepatectomy

Intervention

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
• Penthotal
Intravenous penthotal at the dose of 3 to 5 mg/kg
• Desflurane
Inhaled desflurane aiming an alveolar concentration of 4 to 6 per cent.

Locations

Country	Name	City	State
France	Surgical Intensive Care Unit - Rennes University Hospital	Rennes

Sponsors (2)

Lead Sponsor	Collaborator
Rennes University Hospital	Ministry of Health, France

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Plasma MDA levels		30 minutes after the end of hepatic clamping	No
Secondary	Kinetics of post surgical biological hepatic function recovery	Gamma gluatamyltransferase; ASAT; ALAT; Factor V; AlfagluthationeS-transferase	Days 1, 2, 5, 10	No
Secondary	Kinetics of post surgical hepatic function recovery	Monoethylglycinexylidide (MEGX) test	Day 2	No
Secondary	Other biological markers of oxidative stress	Glutathione; Myeloperoxidase; Nitric oxide	Days 1 and 2	No
Secondary	Hemodynamics during and after surgery	Mean arterial pressure; Heart rate; Diuresis	Days 1 and 2	No
Secondary	Surgery related complications	Liver insufficiency; Hepato renal syndrome; Local infections	10 days	No