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

The depletion of thiols in pancreatic acinar cells, as a consequence o f oxidative stress, seems to underlie acute pancreatitis. Therefore, i mmediate parenteral treatment with agents to refurbish tissue thiols s hould accelerate recovery. We tested this hypothesis in a randomised c linical trial of 79 consecutive patients with a first episode of pancr eatitis. All patients received optimal supportive care. Additional act ive treatment was given for the first 24 hours after admission, accord ing to a randomisation procedure that was applied separately to subgro ups 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-acetylcys teine 300 mg/kg, through separate intravenous lines. Regardless of whe ther it was started within or after 15 hours of the first symptom, the re was no impact on outcome as gauged from reduction in APACHE II scor es 48 hours later, complication rate, days in hospital or mortality at tributable 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 phag ocytosis, and permutations and combinations of these factors.