High-dose allopurinol for prevention of post-ERCP pancreatitis: a prospective randomized double-blind controlled trial.
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.
Katsinelos
Panagiotis
P
Department of Endoscopy and Motility Unit, Central Hospital, Thessaloniki, Greece.
Kountouras
Jannis
J
Chatzis
Josef
J
Christodoulou
Kiriakos
K
Paroutoglou
George
G
Mimidis
Kostas
K
Beltsis
Athanasios
A
Zavos
Christos
C
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000493:Allopurinol / Q000008:administration & dosage*; D002760:Cholangiopancreatography, Endoscopic Retrograde / Q000009:adverse effects*; D004311:Double-Blind Method; D005260:Female; D016166:Free Radical Scavengers / Q000008:administration & dosage*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010195:Pancreatitis / Q000209:etiology* / Q000517:prevention & control*; D011446:Prospective Studies
D016166:Free Radical Scavengers; D000493:Allopurinol