Pharmacological Prevention of Post-Endoscopic Retrograde Cholangiopancreatography Pancreatitis

Abstract

The incidence of clinically significant pancreatitis after endoscopic retrograde cholangiopancreatography (ERCP) ranges from 1-13.5%. It is more common after therapeutic procedures such as sphincterotomy or balloon dilatation of the sphincter, and diagnostic procedures such as biliary or pancreatic manometry. The severity of post-ERCP pancreatitis may vary from very mild to extremely severe disease with multiple organ failure and fatal outcome. Several factors including papillary oedema, injection of hyperosmolar contrast-material, introduction of previously activated enzymes during repeated cannulation, bacterial contamination and thermal injury from endoscopic sphincterotomy have been implicated as triggering factors that initiate the sequential cascade of pancreatic autodigestion and release of proinflammatory cytokines leading to acute pancreatitis. Recovery from post-ERCP pancreatitis is usually rapid when the injury is confined to the pancreas. However, systemic production of inflammatory mediators may lead to the development of more serious manifestations including multiorgan failure.A wide range of pharmacological agents has been tested in experimental and clinical trials, but the results have been largely disappointing. Several drugs are discussed in this review, but only somatostatin and gabexate (gabexate mesilate) have consistently shown a moderate beneficial effect. In clinical trials, both gabexate and somatostatin appear equally effective in reducing the incidence of pancreatitis by two-thirds compared with controls. However, both drugs need to be given by continuous infusion for about 12 hours and this makes them less cost-effective than conventional treatment. One potential strategy is to reserve these drugs for high-risk patients undergoing ERCP. Preliminary studies have shown encouraging results with nitroglycerin, antibacterials and heparin. However, these observations need to be corroborated in a rigorous fashion in large, randomised, double-blind, controlled trials. If these drugs are found to be effective in further trials, it may become cost-effective to use them routinely for the prevention of post-ERCP pancreatitis. Despite the theoretical benefits, interleukin-10 has not shown a consistent benefit in clinical trials. It is probable that other cytokine inhibitors or modulators may become available for future trials to prevent pancreatitis or more probably, to reduce the severity of pancreatitis. Further research also should focus on developing newer molecules or the use of a combination of currently available drugs to prevent pancreatitis in high-risk patients undergoing therapeutic ERCP procedures.

Clinical trial of gabexate in the prophylaxis of post-endoscopic retrograde cholangiopancreatography pancreatitis

“…The ideal prophylactic agent should have the following characteristics: i) be effective in the majority of patients; ii) be inexpensive; iii) be able to be administered on the day of the procedure, and preferably 30-60 min before the procedure; iv) not requiring prolonged administration after the procedure, and v) not increasing the pressure of the sphincter of Oddi (14).…”

“…It has a half-life of 55 s, is widely distributed and is eliminated in the inactive form by the kidneys. Gabexate inhibits trypsin, kallikrein and plasmin, thrombin, phospholipase A2, and C1 esterase (14). Studies on experimental animals and humans have demonstrated that prophylactic administration of gabexate prevents acute pancreatitis (15)(16)(17).…”

Ectopic pancreaticobiliary drainage accompanied by proximal jejunal adenoma: A case report

“…Multiple modalities permit depiction of the anatomy and lesions of the PDDU, including abdominal ultrasonography, ERCP, CT and MRI. Sonographic images often do not clearly display PBM and ectopic termination of the CBD, and ERCP is invasive and can be associated with significant complications, such as a 1% to 13.5% incidence of post-ERCP pancreatitis [12] . In contrast, MDCT and MRI are modern and non-invasive techniques revealing more anatomical details with no risk of procedure-induced complications.…”

Usefulness of axial planes of helical computed tomography for diagnosis of pancreaticobiliary maljunction in early infants with negative findings on magnetic resonance cholangiopancreatography

“…Abdominal ultrasonography is the appropriate initial imaging method for choledochal cysts, but sonographic images often do not clearly display PBM and the common channels [5]. Endoscopic retrograde cholangiopancreatography has been used for this purpose; however, this method is invasive and can be associated with significant complications, such as the 1% to 13.5% incidence of post-ERCP pancreatitis [6]. Therefore, ERCP is contraindicated in some children who have choledochal cysts present with severe acute pancreatitis or cholangitis because it can seriously aggravate any existing inflammation.…”