Effects of Propofol on Oxidative Stress and Liver Regeneration After Partial Hepatectomy - Full Text View

Sponsors and Collaborators:	Rennes University Hospital Ministry of Health, France
Information provided by:	Rennes University Hospital
ClinicalTrials.gov Identifier:	NCT00219856

Purpose

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.

Condition	Intervention	Phase
Hepatectomy	Drug: Propofol Drug: Penthotal	Phase III

MedlinePlus related topics: Anesthesia

Drug Information available for: Propofol I 653

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Single Blind (Subject), Active Control, Parallel Assignment, Safety/Efficacy Study
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

Further study details as provided by Rennes University Hospital:

Primary Outcome Measures:

Plasma MDA levels [ Time Frame: 30 minutes after the end of hepatic clamping ]

Secondary Outcome Measures:

Kinetics of post surgical hepatic function recovery [ Time Frame: Days 1, 2, 5, 10 ]
Gamma glutamyltransferase, ASAT, ALAT, factor V, alpha gluthatione S-transferase [ Time Frame: Days 1, 2, 5, 10 ]
Monoethylglycinexylidide (MEGX) test [ Time Frame: Day 2 ]
Other biological markers of oxidative stress [ Time Frame: Days 1 and 2 ]
Glutathione, myeloperoxidase, nitric oxide [ Time Frame: Days 1 and 2 ]
Hemodynamics during and after surgery [ Time Frame: Day 1 ]
Mean arterial pressure, heart rate, diuresis [ Time Frame: Days 1 and 2 ]
Surgery related complications [ Time Frame: 10 days ]
Liver insufficiency [ Time Frame: 10 days ]
Hepato renal syndrome [ Time Frame: 10 days ]
Infections [ Time Frame: 10 days ]

Enrollment:	34
Study Start Date:	August 2004
Study Completion Date:	March 2006

Arms	Assigned Interventions
1: Experimental Anesthesic induction with intravenous propofol	Drug: Propofol Intravenous propofol aiming a concentration of 4 to 8 µg/ml
2: Active Comparator Anesthesic induction with intravenous penthotal	Drug: Penthotal Intravenous penthotal aiming at the dose of 3 to 5 mg/kg

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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

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

Exclusion 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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00219856

Locations

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

Sponsors and Collaborators

Rennes University Hospital

Ministry of Health, France

Investigators

Principal Investigator:	David Aguillon, MD	CHU de Rennes
Study Director:	Yannick Malledant, MD	CHU de Rennes
Study Chair:	Bruno Laviolle, MD	CHU de Rennes

More Information

Study ID Numbers:	AFSSAPS 040366, PHRC/03-02, CIC0203/026
Study First Received:	September 13, 2005
Last Updated:	November 21, 2007
ClinicalTrials.gov Identifier:	NCT00219856
Health Authority:	France: Afssaps - French Health Products Safety Agency

Keywords provided by Rennes University Hospital:

Propofol
Hepatectomy
Oxidative stress

Study placed in the following topic categories:

Desflurane
Stress
Propofol

Additional relevant MeSH terms:

Anesthetics, Intravenous
Anesthetics, General
Therapeutic Uses
Hypnotics and Sedatives
Physiological Effects of Drugs

Central Nervous System Depressants
Anesthetics
Central Nervous System Agents
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 15, 2009