Papillary Epinephrine Injection vs Rectal Indomethacin

Summary

Post-endoscopic retrograde cholangiopancreatography pancreatitis (PEP) is the most common and one of the most undesirable major adverse events after endoscopic retrograde cholangiopancreatography (ERCP), causing significant morbidity and even mortality. The incidence rate is almost 15% in high-risk patients and no less than 3% in average-risk patients. Many factors contribute to PEP, such as patient-related and endoscopist-related factors, but mainly two mechanisms are considered in terms of physiopathology: papillary edema caused by mechanical trauma during cannulation and thermal injury with electrocautery current. Rectal NSAIDs and pancreatic stent placement are the two proven methods of PEP prophylaxis included in the guideline recommendations, but despite their frequent use, the incidence rates remain unacceptably high. There is a need for additional methods that are easy to implement, preferably low-cost, and safe to reduce the risk of PEP. Topical epinephrine applied submucosally can meet these goals. Ampullary epinephrine injection is an effective method for post-sphincterotomy bleeding. Still, to our knowledge, no study has examined its efficacy in PEP prophylaxis, except for the retrospective study we reported. There are conflicting reports on epinephrine spraying onto the papilla for PEP, but these trials are largely heterogeneous, with different dose regimens. It should also be noted that spraying epinephrine onto the papilla has a duration of action of about 1 to 5 minutes, whereas epinephrine injection has a duration of roughly 120 minutes. Given this information, a large-scale, prospective, double-blind, randomized, controlled trial is designed.

Timeline

Start

2023-01-01

Primary completion

2025-03-01

Completion

2025-05-01

Publications

• Background Andriulli A, Loperfido S, Napolitano G, Niro G, Valvano MR, Spirito F, Pilotto A, Forlano R. Incidence rates of post-ERCP complications: a systematic survey of prospective studies. Am J Gastroenterol. 2007 Aug;102(8):1781-8. doi: 10.1111/j.1572-0241.2007.01279.x. Epub 2007 May 17.
• Background Kochar B, Akshintala VS, Afghani E, Elmunzer BJ, Kim KJ, Lennon AM, Khashab MA, Kalloo AN, Singh VK. Incidence, severity, and mortality of post-ERCP pancreatitis: a systematic review by using randomized, controlled trials. Gastrointest Endosc. 2015 Jan;81(1):143-149.e9. doi: 10.1016/j.gie.2014.06.045. Epub 2014 Aug 1.
• Background Pezzilli R, Romboli E, Campana D, Corinaldesi R. Mechanisms involved in the onset of post-ERCP pancreatitis. JOP. 2002 Nov;3(6):162-8.
• Background Dumonceau JM, Kapral C, Aabakken L, Papanikolaou IS, Tringali A, Vanbiervliet G, Beyna T, Dinis-Ribeiro M, Hritz I, Mariani A, Paspatis G, Radaelli F, Lakhtakia S, Veitch AM, van Hooft JE. ERCP-related adverse events: European Society of Gastrointestinal Endoscopy (ESGE) Guideline. Endoscopy. 2020 Feb;52(2):127-149. doi: 10.1055/a-1075-4080. Epub 2019 Dec 20.
• Background Torun S, Odemis B, Cetin MF, Onmez A, Coskun O. Efficacy of Epinephrine Injection in Preventing Post-ERCP Pancreatitis. Surg Laparosc Endosc Percutan Tech. 2020 Oct 12;31(2):208-214. doi: 10.1097/SLE.0000000000000867.
• Background Akshintala VS, Hutfless SM, Colantuoni E, Kim KJ, Khashab MA, Li T, Elmunzer BJ, Puhan MA, Sinha A, Kamal A, Lennon AM, Okolo PI, Palakurthy MK, Kalloo AN, Singh VK. Systematic review with network meta-analysis: pharmacological prophylaxis against post-ERCP pancreatitis. Aliment Pharmacol Ther. 2013 Dec;38(11-12):1325-37. doi: 10.1111/apt.12534. Epub 2013 Oct 20.
• Background Aziz M, Ghanim M, Sheikh T, Sharma S, Ghazaleh S, Fatima R, Khan Z, Lee-Smith W, Nawras A. Rectal indomethacin with topical epinephrine versus indomethacin alone for preventing Post-ERCP pancreatitis - A systematic review and meta-analysis. Pancreatology. 2020 Apr;20(3):356-361. doi: 10.1016/j.pan.2020.02.003. Epub 2020 Feb 19.
• Background Igawa M, Miyaoka M, Saitoh T. Influence of topical epinephrine application on microcirculatory disturbance in subjects with ulcerative colitis evaluated by laser Doppler flowmetry and transmission electron microscopy. Dig Endosc. 2000;12:126-130
• Background Chung SC, Leung JW, Leung FW. Effect of submucosal epinephrine injection on local gastric blood flow. A study using laser Doppler flowmetry and reflectance spectrophotometry. Dig Dis Sci. 1990 Aug;35(8):1008-11. doi: 10.1007/BF01537250.

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