Prevention Effect of Allopurinol on Post-Endoscopic Retrograde Cholangiopancreatography Pancreatitis: A Meta-Analysis of Prospective Randomized Controlled Trials

Abstract

BackgroundPancreatitis is the most common complication of endoscopic retrograde cholangiopancreatography (ERCP) which can be severe and cause death in approximately 10% of cases. Up to now, six randomized controlled trials (RCTs) have been found relevant to the effect of allopurinol on prevention of Post-ERCP pancreatitis (PEP). However, these results remained controversial.ObjectiveTo conduct a meta-analysis with RCTs published in full text to determine the effectiveness of prophylactic allopurinol of different dosages and administration time in the incidence and severity of PEP.MethodsLiterature search was performed in PubMed, Embase, Web of Science and Cochrane Library from databases inception to May 2014. RCTs comparing the effect of allopurinol with placebo on prevention of PEP were included. Statistical heterogeneity was quantitatively evaluated byχ2 test with the significance set P<0.10 or I2>50%.ResultsSix RCTs consisting of 1974 participants were eventually included. The incidences of PEP in allopurinol group and placebo group were 8.4%(83/986) and 9.9%(98/988) respectively. Meta-analysis showed no evident prevention effect of allopurinol on the incidence of PEP (RR 0.75, 95%CI 0.39–1.42) with significant heterogeneity (I2 = 70.4%, P = 0.005). When studies were stratified according to the dosages and administration time of allopurinol they applied, there was still no evident prevention effect of allopurinol on mild, moderate or severe PEP. However, statistically substantial heterogeneity was presented in the subgroup of moderate PEP when the effect of high dose of allopurinol was analyzed (Imoderate 2 = 82.3%, Pmoderate = 0.018). Statistically significant heterogeneity was also observed in subgroup of mild PEP, when the effect of long adminstration time of allopurinol was investigated (Imild 2 = 62.8%, Pmild = 0.068).ConclusionThe prophylactic use of allopurinol in different dosages and administration time had no effect in preventing incidence and severity of PEP.

Comparative Efficacy of 9 Major Drugs for Postendoscopic Retrograde Cholangiopancreatography Pancreatitis: A Network Meta-Analysis

“…52 Allopurinol inhibits the production of oxygen-derived free radicals which play an important role in the progression of pancreatitis. 53 Consistent with a previous meta-analysis of 6 studies, 54 our results demonstrated that allopurinol did not lower the risk of PEP.…”

Recent advances in understanding and managing acute pancreatitis

“…Chemoprevention of PEP using a variety of other agents has not been fruitful. The most recent meta-analyses and RCTs have demonstrated that allopurinol 103 , corticosteroids 104 – 106 , somatostatin and their analogues 107 , heparin 108 , and nitroglycerin 87 , 109 have an inconclusive or non-significant effect on reducing the risk of PEP. Whereas the protease inhibitor nafamostat reduces the risk of PEP 87 , 110 , it does not reduce the risk of PEP in high-risk patients, has a high cost, and requires a prolonged 7- to 25-hour infusion that diminishes the practicality of offering this to patients 110 .…”

Recent advances in understanding and managing acute pancreatitis

“…The most recent meta-analyses and RCTs have demonstrated that allopurinol 102 , corticosteroids 103– 105 , somatostatin and their analogues 106 , heparin 107 , and nitroglycerin 86, 108 have an inconclusive or non-significant effect on reducing the risk of PEP. Whereas the protease inhibitor nafamostat reduces the risk of PEP 86, 109 , it does not reduce the risk of PEP in high-risk patients, has a high cost, and requires a prolonged 7- to 25-hour infusion that diminishes the practicality of offering this to patients 109 .…”