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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Hepatectomy

Intervention / Treatment
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* Drug: Propofol
* Drug: Penthotal
* Drug: Desflurane


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Anesthesic induction and maintenance with intravenous propofol. | Drug: Propofol<br>* Induction : intravenous propofol aiming a concentration of 4 to 8 µg/ml Maintenance : intravenous propofol aiming a concentration of 3 to 6 µg/ml<br>|
| Active Comparator: 2<br>Anesthesic induction with intravenous penthotal and maintenance with inhaled desflurane. | Drug: Penthotal<br>* Intravenous penthotal at the dose of 3 to 5 mg/kg<br>Drug: Desflurane<br>* Inhaled desflurane aiming an alveolar concentration of 4 to 6 per cent.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma MDA levels |  | 30 minutes after the end of hepatic clamping | 

Secondary Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Propofol, Hepatectomy, Oxidative stress