N-acetylcysteine to Reduce Ischemia/Reperfusion Injury in Liver Resection

Study Overview
=================
Brief Summary
-----------------
Study hypothesis: N-acetylcysteine (NAC) can reduce ischemia/reperfusion injury in liver resection performed under ischemic preconditioning and intermittent portal triad clamping.

Detailed Description
-----------------
One of the most important factors in the pathophysiology of liver dysfunction after hepatic surgery is the cellular damage derived from the interruption of blood flood with reperfusion of the organ. N-acetylcysteine (NAC) has proved beneficial in several conditions involving oxidative damage. This study investigates the effects of NAC to reduce ischemia/reperfusion injury in liver resection performed under ischemic preconditioning and intermittent portal triad clamping. Methods: 46 ASA II-III patients scheduled to undergo liver resection where randomised to receive NAC (initial dose: 150 mg/Kg; and infusion of 50 mg/kg, from 30 minutes before the ischemia up to 60 minutes later to the reperfusion) or placebo in a phase IV clinical trial. Blood, hepatic and urinary markers were obtained at basal status and 1, 3 and 24 h post final reperfusion.

Official Title
-----------------
A Randomized Controlled Trial of N-acetylcysteine to Reduce Ischemia/Reperfusion Injury in Liver Resection Performed Under Ischemic Preconditioning and Intermittent Portal Triad Clamping

Conditions
-----------------
Hepatectomy, Reperfusion Injury

Intervention / Treatment
-----------------
* Drug: Acetylcysteine (NAC)
* Drug: Saline


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Hepatectomy Exclusion Criteria: ASA 4 Cirrhosis Creatinine > 1.2 mg/dL Associate surgery (pancreatic or splenectomy) Intraoperative bleeding > 2 L. Active infection of inflammatory disease

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: N-acetylcysteine<br>Intravenous N-acetylcysteine | Drug: Acetylcysteine (NAC)<br>* NAC 150 mg/Kg; and infusion of 50 mg/kg, from 30 minutes before the ischemia up to 60 minutes later to the reperfusion<br>* Other names: Flumil;|
| Placebo Comparator: Placebo<br>Placebo | Drug: Saline<br>* Na Cl 0.9% infusion<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Laboratory results | Coagulation + cytolysis + cholestasis + lactic acid | 24 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Inflammation | Cytokines, adhesion molecules (P-selectin and ICAM-1) and nuclear factor kappaB (NF-kappaB). Circulating neutrophils/platelets. Oxidative stress of neutrophils and apoptosis. | 24 hours | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Acetylcysteine