Methylprednisolone N Acetylcysteine in Hepatic Resections
Status:
Terminated
Trial end date:
2013-11-01
Target enrollment:
Participant gender:
Summary
This is a prospective double-blind randomized phase II clinical trial, with two groups of
intervention (one with administration of N-acetylcysteine and the other with administration
of methylprednisolone), and one group of placebo. The purpose of this study is to investigate
the role of N-acetylcysteine and Methylprednisolone in the modulation of warm ischemia of the
liver during hepatic resection. In fact to avoid massive blood loss in liver surgery,
continuous or intermittent vascular clamping of the hepatic hilum ('Pringle maneuver') is
generally used with good results. However, as a consequence, ischemia and subsequent
reperfusion result in complex metabolic, immunological, and microvascular changes, which
together might contribute to hepatocellular damage and dysfunction. This phenomenon, known as
ischemia-reperfusion (IR) injury of the liver, is a complex multi-path process leading to the
activation of some inflammatory pathways. Any patient candidate to liver resection will be
enrolled in the study based on the aforementioned criteria. The primary objective of the
study is to assess the real efficacy of Methylprednisolone and N-acetylcysteine in reducing
the secondary damage from ischemia reperfusion injury in liver resection and in reducing
inflammatory response. Secondary objective of the study is whether the reduction of
ischemia-reperfusion injury results in: lower incidence of postoperative liver failure,
improvement of postoperative liver function, and reduction of blood components transfusions.
The randomization will be done the day before the operation. The drugs will be prepared in a
blind fashion by the hospital pharmacy. The hospital pharmacy will provide to each patient a
drip to make bolus of about an hour before the start of the liver resection and a syringe
pump for an infusion of approximately 6 hours. If the patient is enrolled and randomized in
the placebo arm, he/she will receive 250 ml of glucose 5% plus the infusion of 100 ml of
glucose 5% If the patient is randomized in the Methylprednisolone arm, he/she will receive a
dose of 500 mg in 250 ml of glucose 5% plus 100 mg of glucose 5%. If the patient is
randomized in the N-acetylcysteine arm, he/she will receive a dose of 150 mg/kg in 250 ml of
glucose 5% plus N-acetylcysteine 50 mg/kg in 100 ml glucose 5%. Systematic sampling of liver
function tests will be done the day before the operation, at the end of the operation, as
well as in postoperative day 1, 3, 5 and 7.