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

This study has been completed.
Sponsor:
Collaborator:
Ministry of Health, France
Information provided by:
Rennes University Hospital
ClinicalTrials.gov Identifier:
NCT00219856
First received: September 13, 2005
Last updated: June 25, 2012
Last verified: June 2012
History of Changes
  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
Drug: Desflurane
 Phase 3

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

Resource links provided by NLM:

U.S. FDA Resources

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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Kinetics of post surgical biological hepatic function recovery [ Time Frame: Days 1, 2, 5, 10 ] [ Designated as safety issue: No ]
    • Gamma gluatamyltransferase
    • ASAT
    • ALAT
    • Factor V
    • AlfagluthationeS-transferase

  • Kinetics of post surgical hepatic function recovery [ Time Frame: Day 2 ] [ Designated as safety issue: No ]
    Monoethylglycinexylidide (MEGX) test

  • Other biological markers of oxidative stress [ Time Frame: Days 1 and 2 ] [ Designated as safety issue: No ]
    • Glutathione
    • Myeloperoxidase
    • Nitric oxide

  • Hemodynamics during and after surgery [ Time Frame: Days 1 and 2 ] [ Designated as safety issue: No ]
    • Mean arterial pressure
    • Heart rate
    • Diuresis

  • Surgery related complications [ Time Frame: 10 days ] [ Designated as safety issue: No ]
    • Liver insufficiency
    • Hepato renal syndrome
    • Local infections


Enrollment: 34
Study Start Date: August 2004
Study Completion Date: March 2006
Primary Completion Date: March 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

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 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
  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

No publications provided

Responsible Party: Direction of Clinical Research, Rennes University Hospital
ClinicalTrials.gov Identifier: NCT00219856     History of Changes
Other Study ID Numbers: AFSSAPS 040366, PHRC/03-02, CIC0203/026
Study First Received: September 13, 2005
Last Updated: June 25, 2012
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by Rennes University Hospital:
Propofol
Hepatectomy
Oxidative stress

Additional relevant MeSH terms:
Propofol
Desflurane
Anesthetics, Intravenous
Anesthetics, General
Anesthetics
Central Nervous System Depressants
 Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Hypnotics and Sedatives
Anesthetics, Inhalation

ClinicalTrials.gov processed this record on May 19, 2013