Siriwardena AK et al. (2007) Randomised, double blind, placebo controlled trial of intravenous antioxidant (n-acetylcysteine, selenium, vitamin C) therapy in severe acute pancreatitis. Gut 56: 1439–1444

Experiments in rats have demonstrated that combination antioxidant therapy given after induction of acute pancreatitis reduces pancreatic and remote organ injury. Owing to such observations, and despite a lack of convincing clinical data, patients with severe acute pancreatitis have been treated with intravenous antioxidant therapy. Siriwardena et al., therefore, conducted a randomized, double blind, placebo-controlled trial of intravenous antioxidant therapy in patients with severe acute pancreatitis.

Patients (n = 43) were enrolled between June 2001 and November 2004 from three UK hospitals; all had predicted severe acute pancreatitis defined as an APACHE II score of ≥8 at admission or within 48 h of admission. All patients were enrolled within 72 h of admission. Randomization was stratified for APACHE II score and hospital site. Antioxidant group patients (n = 22) received maximal conventional therapy plus intravenous antioxidant (N-acetylcysteine, selenium, and vitamin C) therapy for 7 days, whereas placebo group patients (n = 21) received maximal conventional therapy plus intravenous placebo for the same period of time.

Antioxidant therapy did not reduce the occurrence of organ dysfunction at 7 days, improve patient outcome or reduce the length of hospital stay. In addition, the study was terminated early (after year 3) because all deaths that occurred were in the antioxidant group (4 vs 0). Although the study was underpowered, the data suggested that antioxidant therapy might be harmful in patients with multiple organ dysfunction at baseline.

The findings of Siriwardena et al. question the continued use of antioxidant therapy for patients with severe acute pancreatitis.