PANCREAS

Randomised, double blind, placebo controlled trial of intravenous antioxidant (n-acetylcysteine, selenium, vitamin C) therapy in severe acute pancreatitis

Ajith K Siriwardena¹, James M Mason², Srinivasan Balachandra¹, Anil Bagul¹, Simon Galloway³, Laura Formela⁴, Jonathan G Hardman¹, Saurabh Jamdar²

¹ Hepatobiliary Surgery Unit, Department of Surgery, Manchester Royal Infirmary, Manchester, UK
² School for Health, University of Durham, UK
³ Department of Upper GI Surgery, Wythenshawe Hospital, Manchester, UK
⁴ Department of Upper GI Surgery, Hope Hospital, Salford, UK

Correspondence to:
Dr Ajith K Siriwardena
Hepatobiliary Unit, Department of Surgery, Manchester Royal Infirmary, Manchester M13 9WL, UK; ajith.siriwardena{at}cmmc.nhs.uk

Background: Based on equivocal clinical data, intravenous antioxidant therapy has been used for the treatment of severe acute pancreatitis. To date there is no randomised comparison of this therapy in severe acute pancreatitis.

Methods: We conducted a randomised, double blind, placebo controlled trial of intravenous antioxidant (n-acetylcysteine, selenium, vitamin C) therapy in patients with predicted severe acute pancreatitis. Forty-three patients were enrolled from three hospitals in the Manchester (UK) area over the period June 2001 to November 2004. Randomisation stratified for APACHE-II score and hospital site, and delivered groups that were similar at baseline.

Results: Relative serum levels of antioxidants rose while markers of oxidative stress fell in the active treatment group during the course of the trial. However, at 7 days, there was no statistically significant difference in the primary end point, organ dysfunction (antioxidant vs placebo: 32% vs 17%, p = 0.33) or any secondary end point of organ dysfunction or patient outcome.

Conclusions: This study provides no evidence to justify continued use of n-acetylcysteine, selenium, vitamin C based antioxidant therapy in severe acute pancreatitis. In the context of any future trial design, careful consideration must be given to the risks raised by the greater trend towards adverse outcome in patients in the treatment arm of this study.

Abbreviations: CRFs, case report forms; ERC, endoscopic retrograde cholangiography; GSH, glutathione; GSSG, glutathione disulphide; HDU, high dependency unit; HO-1, haem oxygenase; IQR, interquartile range; ITU, intensive care unit; LODS, logistic organ dysfunction score; MODS, Marshall organ dysfunction score; MT-1, metallothionein

Keywords: pancreatitis; antioxidants; randomised controlled trial

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