Effect of Transdermal Glyceryl-Trinitrate and Parecoxib (Valdecoxib) for the Prevention of Post -ERCP Pancreatitis

Acute pancreatitis represents the most common complication after ERCP. The reported incidence of this complication varies from less than 1% to 40%, but rates of about 10% are reported in most prospective studies involving non-selected patients. Although most episodes (about 90%) of post-ERCP pancreatitis are mild, a small percentage of patients (about 10%) may develop severe pancreatitis resulting in significant morbidity and occasional mortality. Despite technical improvements in recent years, the incidence of this complication has not decreased.

The risk factors for development of post ERCP acute pancreatitis are now well known. Balloon dilatation of sphincter of Oddi, difficult papillary cannulation, pancreatic sphincterotomy and multiple pancreatic duct injections have been found to be independent risk factors for post-procedure pancreatitis (Odds ratio of 4.5, 3.4, 3.1, 2.7 respectively) in a recent prospective, multicenter study by Freeman et al. Opacification of the main pancreatic duct alone (MPD) is associated with a 31% incidence of hyperamylasemia. This figure is similar to the 24% incidence of hyperamylasemia which occurs after cholangiography alone. However both injection pressure and volume of contrast medium injected into the pancreatic duct contribute to ductal epithelial or acinar injury by disruption of the intercellular tight junctions with a backflow into the interstitial space.

The role of the osmolarity and ionic nature of the contrast medium is controversial. However non-ionic, low osmolarity contrast media is preferred by most endoscopists. Electrocautery in the vicinity of the MPD orifice may produce edema of the tissues with subsequent obstruction. Etta et al recently showed that use of pure cutting current significantly reduced pancreatitis rates when compared with blended current (3% vs 11%).Precut or access papillotomy is associated with higher risk of pancreatitis when used by endoscopists with less experience, but not in the hands of experienced endoscopists.Operator experience also seems to be a potential risk factor for post ERCP complications. Large volume centers performing > 200 procedures per year had significantly less overall complications (2.0% vs 7.1%, p<0.001) and less complication related deaths (0.18% vs 0.75%, p<0.05), compared to low volume centers in a large Italian multicenter prospective study.

Various agents have been tried with an aim to prevent post ERCP pancreatitis in the last 10 years. These include Gabexate, Somatostatin, Nifedipine, Octreotide, Hydrocortisone, Prednisone, Allopurinol, Interleukin-10, and Methylprednisolone which have been evaluated in randomized controlled studies.Of these agents only Interleukin-10, Somatostatin and Gabexate have been found efficacious. However 13 patients need to be treated prophylactically with Somatostatin and 27 with Gabexate to prevent a single case of post ERCP pancreatitis. Hence these agents are unlikely to be cost-effective or universally applicable. The ideal agent to prevent this complication should be cheap, widely applicable and have a rational basis.

It has been found that cannulation trauma to the papilla or electrocautery leads to sphincter of Oddi spasm and/or papillary edema, thus obstructing free flow of pancreatic juice and contrast with resultant acute pancreatic inflammation.