Original Article
High-dose allopurinol for prevention of post-ERCP pancreatitis: a prospective randomized double-blind controlled trial

https://doi.org/10.1016/S0016-5107(04)02647-1Get rights and content

Background

Pancreatitis is the most common major complication of diagnostic and therapeutic ERCP. Allopurinol, a xanthine oxidase inhibitor that blocks generation of oxygen-derived free radicals, potentially may prevent post-ERCP pancreatitis. This study assessed the efficacy of high-dose oral allopurinol for prevention of post-ERCP pancreatitis.

Methods

A prospective, double-blind, placebo-controlled trial was conducted in 250 patients undergoing ERCP. Patients were randomized to receive allopurinol (600 mg) or placebo orally at 15 and 3 hours before the procedure. Patients were clinically evaluated, and serum amylase levels were determined before ERCP and at 6 and 24 hours thereafter. Standardized criteria were used to diagnose and to grade the severity of post-ERCP pancreatitis.

Results

A total of 243 patients were included in the analysis. The two groups were similar with regard to age; gender; underlying disease; indication for treatment; ERCP findings; and type of treatment, except for biliary sphincterotomy. Only 43 patients in the allopurinol group underwent biliary sphincterotomy vs. 87 in the placebo group (p < 0.001). The frequency of acute pancreatitis was significantly lower in the allopurinol vs. the placebo group in the final multinomial regression analysis: allopurinol group, 4/125 (3.2%), with all 4 cases graded as mild, vs. placebo group, 21/118 (17.8%), of which 8/118 (6.8%) were graded as mild, 11/118 (9.3%) as moderate, and 2/118 (1.6%) as severe with fatal outcome (p < 0.001). The protective effect of allopurinol was also apparent in the diagnostic ERCP and the biliary sphincterotomy subgroups when the frequency of post-ERCP pancreatitis was analyzed after stratification by procedure. The mean duration of hospitalization for pancreatitis was significantly shorter in the allopurinol compared with the placebo group (2.5 vs. 5.67 days; p < 0.001).

Conclusions

Pretreatment with high-dose, orally administered allopurinol decreases the frequency of post-ERCP pancreatitis. Despite the promising results of this prospective, randomized trial, further studies are needed to verify these observations before allopurinol can be recommended for routine clinical use.

Section snippets

Patients

A double-blind, randomized, placebo-controlled trial was carried out with 250 consecutive patients undergoing diagnostic or therapeutic ERCP during a 16-month period (January 1999 to April 2000). Exclusion criteria were the following: (1) acute pancreatitis (patients undergoing early ERCP during the acute phase), (2) age less than 18 years, (3) history of allergy to allopurinol, (4) acute myocardial infarction within 3 months before ERCP, (5) other severe systemic disease, (6) pregnancy or

Results

Duodenal intubation was unsuccessful in 7 patients because of duodenal distortion (n = 1), a previous gastrectomy with Billroth II anastomosis (n = 4), or refusal to undergo ERCP (n = 2). These patients had been randomized to the placebo group and were excluded from analysis.

Multinomial regression by stepwise analysis revealed that the factors related to post-ERCP pancreatitis were male gender (p < 0.001), days of hospitalization (p < 0.001), in the sense that more days were required for the patients

Discussion

Although the exact mechanism(s) leading to post-ERCP pancreatic injury is unknown, there is great interest in pharmacologic treatment aimed at modulating the inflammatory mediators and activation of proteolytic enzymes thought to be involved in the development and the propagation of pancreatitis. Trials of prophylactic agents, including calcitonin,21 corticosteroid,9 glucagon,22 and nifedipine23 have failed to show benefit with respect to prevention of post-ERCP pancreatitis. A meta-analysis of

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