CLINICAL-TRIAL OF 24 HOURS TREATMENT WITH GLUTATHIONE PRECURSORS IN ACUTE-PANCREATITIS

The depletion of thiols in pancreatic acinar cells, as a consequence of oxidative stress, seems to underlie acute pancreatitis. Therefore, immediate parenteral treatment with agents to refurbish tissue thiols should accelerate recovery. We tested this hypothesis in a randomised clinical trial of 79 consecutive patients with a first episode of pancreatitis. All patients received optimal supportive care. Additional active treatment was given for the first 24 hours after admission, according to a randomisation procedure that was applied separately to subgroups classified as mild or severe, based on admission APACHE II scores < or greater than or equal to 8, respectively. The treatment consisted of S-adenosylmethionine (SAMe; ademetionine) 43 mg/kg and N-acetylcysteine 300 mg/kg, through separate intravenous lines. Regardless of whether it was started within or after 15 hours of the first symptom, there was no impact on outcome as gauged from reduction in APACHE II scores 48 hours later, complication rate, days in hospital or mortality attributable to pancreatitis. This inefficacy may reflect the inevitable time-lag to admission, insufficient duration of treatment, failure to correct deficiencies of other antioxidants, the injurious effects of inflammatory mediators discharged extracellularly from frustrated phagocytosis, and permutations and combinations of these factors.