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Pharmacological Prevention of Post-Endoscopic Retrograde Cholangiopancreatography Pancreatitis

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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.

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No sources of funding were used to assist in the preparation of this manuscript. The authors have no conflicts of interest that are directly relevant to the content of this manuscript.

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  1. Division of Gastroenterology & Hepatology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA

    Hemant Pande &  Paul J. Thuluvath

  2. Division of Gastroenterology, The Johns Hopkins Hospital, Room 429, 1830 E. Monument Street, Baltimore, Maryland, 21205, USA

    Hemant Pande &  Paul J. Thuluvath

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Pande, H., Thuluvath, P.J. Pharmacological Prevention of Post-Endoscopic Retrograde Cholangiopancreatography Pancreatitis. Drugs 63, 1799–1812 (2003). https://doi.org/10.2165/00003495-200363170-00003

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