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Prophylaxis of pancreatitis with intravenous ketoprofen in a consecutive population of ERCP patients: a randomized double-blind placebo-controlled trial

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Abstract

Background Acute pancreatitis is the most common complication after ERCP, occurring in about 4 % of the procedures. Only the placement of pancreatic duct prosthesis and the use of nonsteroidal anti-inflammatory drugs (NSAIDs) have shown benefit in the prevention of post-ERCP pancreatitis (PEP). Although the benefit of rectal administration of indomethacin or diclofenac is recommended by some studies and society guidelines especially in a selected group of high-risk patients, there is so far, no standardization of time or route of NSAID administration. The aim of the current study is to investigate the role of an intravenous NSAID administered before the procedure for PEP prevention. Methods In this randomized double-blind clinical trial, all consecutive patients who underwent ERCP were randomized to receive saline infusion with ketoprofen or saline, immediately before the procedure. Results A total of 477 patients were enrolled and completed follow-up. The majority of patients (72.1 %) had bile duct stones, and only 1.5 % had a clinical suspicion of sphincter of Oddi dysfunction. PEP developed in 5 of 253 (2 %) patients in the placebo group and in 5 of 224 (2.2 %) patients in the ketoprofen group (p = 1.). Conclusions Intravenous administration of ketoprofen immediately prior to ERCP did not result in reduction in PEP in a general population of ERCP patients.

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References

  1. Wong LL, Tsai HH (2014) Prevention of post-ERCP pancreatitis. World J Gastrointest Pathophysiol 5:1–10

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Freeman ML, Guda NM (2004) Prevention of post-ERCP pancreatitis: a comprehensive review. Gastrointest Endosc 59:845–864

    Article  PubMed  Google Scholar 

  3. Andriulli A, Loperfido S, Napolitano G, Niro G, Valvano MR, Spirito F, Spirito F, Pilotto A, Forlano R (2007) Incidence rates of post-ERCP complications: a systematic survey of prospective studies. Am J Gastroenterol 102(8):1781–1788

    Article  PubMed  Google Scholar 

  4. Dumonceau JM, Andriulli A, Elmunzer BJ, Mariani A, Meister T, Deviere J, Marek T, Baron TH, Hassan C, Testoni PA, Kapral C (2014) European society of gastrointestinal endoscopy (2014) prophylaxis of post–ERCP pancreatitis: European society of gastrointestinal endoscopy (ESGE) guideline—updated june 2014. Endoscopy 46:799–815

    Article  PubMed  Google Scholar 

  5. ASGE Standards of Practice Committee, Anderson MA, Fisher L, Jain R, Evans JA, Appalaneni V, Ben-Menachem T, Cash BD, Decker GA, Early DS, Fanelli RD, Fisher DA, Fukami N, Hwang JH, Ikenberry SO, Jue TL, Khan KM, Krinsky ML, Malpas PM, Maple JT, Sharaf RN, Shergill AK, Dominitz JA (2012) ASGE Standards of Practice Committee: complications of ERCP. Gastrointest Endosc 75:46–473

    Google Scholar 

  6. Thaker AM, Mosko JD, Berzin TM (2015) Post-endoscopic retrograde cholangiopancreatography pancreatitis. Gastroenterology Report 3:32–40

    Article  PubMed  Google Scholar 

  7. Insel PA (1996) Analgesic-antipyretic and antiinflammatory agents and drugs employed in the treatment of gout. In: Hardman JG, Gilman AG, Limbird LE (eds) Goodman&Gilman’s. The pharmacological basis of therapeutics. Mc-graw hill, New York, pp 617–657

    Google Scholar 

  8. Elmunzer BJ, Sheiman JM, Lehman GA, Chak A, Mosler P, Higgins PD, Hayward RA, Romagnuolo J, Elta GH, Sherman S, Waljee AK, Repaka A, Atkinson MR, Cote GA, Kwon RS, McHenry L, Piraka CR, Wamsteker EJ, Watkins JL, Korsnes SJ, Schmidt SE, Turner SM, Nicholson S, Fogel EL, U.S. Cooperative for Outcomes Research in Endoscopy (USCORE) (2012) A randomized trial of rectal indomethacin to prevent post-ERCP pancreatitis. New Engl J Med 366:1414–1422

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Ding X, Chen M, Huang S, Zhang S, Zou X (2012) Nonsteroidal anti-inflammatory drugs for prevention of post-ERCP pancreatitis: a meta-analysis. Gastrointest Endosc 76:1152–1159

    Article  PubMed  Google Scholar 

  10. Dai HF, Wang XW, Zhao K (2009) Role of nonsteroidal anti-inflammatory drugs in the prevention of post-ERCP pancreatitis: a meta-analysis. Hepatobiliary Pancreat Dis Int 8:11–16

    CAS  PubMed  Google Scholar 

  11. Levenick JM, Gordon SR, Fadden LL, Levy LC, Rockacy MJ, Hyder SM, Lacy BE, Bensen SP, Parr DD, Gardner TB (2016) Rectal indomethacin does not prevent post-ERCP pancreatitis in consecutive patients. Gastroenterology 150(4):911–917

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Hauser G, Blažević I, Salkić N, Poropat G, Giljača V, Bulić Z, Štimac D (2016) Diclofenac sodium versus ceftazidime for preventing pancreatitis after endoscopic retrograde cholangiopancreatography: a prospective, randomized, controlled trial. Surg Endosc [Epub ahead of print]

  13. Cotton PB, Lehman G, Vennes J, Geenen JE, Russell RC, Meyers WC, Liguory C, Nick N (1991) Endoscopic sphincterotomy complications and their management: an attempt at consensus. Gastrointest Endosc 37:383–393

    Article  CAS  PubMed  Google Scholar 

  14. Kent DM, Rothwell PM, Ioannidis JP (2010) Assessing and reporting heterogeneity in treatment effects in clinical trials: a proposal. Trials 11:85–95

    Article  PubMed  PubMed Central  Google Scholar 

  15. Park SW, Chung MJ, Oh TG, Park JY, Bang S, Park SW, Song SY (2015) Intramuscular diclofenac for the prevention of post-ERCP pancreatitis—a randomized trial. Endoscopy 47:33–39

    PubMed  Google Scholar 

  16. Bhatia V, Ahuja V, Acharya SK, Garg PK (2011) A randomized controlled trial of valdecoxib and glyceryl trinitrate for the prevention of post-ERCP pancreatitis. J Clin Gastroenterol 45:170–176

    Article  CAS  PubMed  Google Scholar 

  17. Cheon YK, Cho KB, Watkins JL, McHenry L, Fogel EL, Sherman S, Schmidt S, Lazzell-Pannell L, Lehman GA (2017) Efficacy of diclofenac in the prevention of post-ERCP pancreatitis in predominantly high-risk patients: a randomized double-blind prospective trial. Gastrointest Endosc 66:1126–1132

    Article  Google Scholar 

  18. Torriani MS, Silva RG, Santos L (2003) Vias de administração: o cuidado do farmacêutico na orientação do uso dos medicamentos. In: Santos L, Torriani MS, Barros E (eds) Medicamentos na prática da farmácia clínica. Artmed, Porto Alegre, pp 51–59

    Google Scholar 

  19. Nevalainen TJ, Hietaranta AJ, Gronroos JM (1999) Phospholipase A2 in acute pancreatitis: new biochemical and pathological aspects. Hepato-Gastroenterology 46:2731–2735

    CAS  PubMed  Google Scholar 

  20. Mäkelä A, Kuusi T, Schröder T (1997) Inhibition of serum phospholipase-A2 in acute pancreatitis by pharmacological agents in vitro. Scand J Clin Lab Invest 57:401–407

    Article  PubMed  Google Scholar 

  21. Tiemen S, Steinberg WM (2010) Acute pancreatitis. In: Feldman M, Friedman LS, Brandt LJ, Sleisenger, MH (eds) Sleisenger & Fordtran’s gastrointestinal and liver disease: pathophysiology/diagnosis/management, 9th edn. Saunders Elsevier, Philadelphia, PA, p 959–983

    Google Scholar 

  22. Bai Y, Gao J, Shi X, Zou D, Li Z (2008) Prophylactic corticosteroids do not prevent post-ERCP pancreatitis: a meta-analysis of randomized controlled trials. Pancreatology 8:504–509

    Article  CAS  PubMed  Google Scholar 

  23. Zheng M, Bai J, Yuan B, Lin F, You J, Lu M, Gong Y, Chen Y (2008) Meta-analysis of prophylactic corticosteroid use in post-ERCP pancreatitis. BMC Gastroenterol 8:6

    Article  PubMed  PubMed Central  Google Scholar 

  24. Freeman ML, Nelson DB, Sherman S, Haber GB, Herman ME, Dorsher PJ, Moore JP, Fennerty MD, Ryan ME, Shaw MJ, Lande JD, Pheley AM (1996) Complications of endoscopic biliary sphincterotomy. N Engl J Med 335:909–918

    Article  CAS  PubMed  Google Scholar 

  25. Loperfido S, Angelini G, Benedetti G, Chilovi F, Costan F, De Berardinis F, De Bernardin M, Ederle A, Fina P, Fratton A (1998) Major early complications from diagnostic and therapeutic ERCP: a prospective multicenter study. Gastrointest Endosc 48:1–10

    Article  CAS  PubMed  Google Scholar 

  26. Williams EJ, Taylor S, Fairclough P, Hamlyn A, Logan RF, Martin D, Riley SA, Veitch P, Wilkinson ML, Williamson PR, Lombard M (2007) Risk factors for complication following ERCP; results of a large-scale, prospective multicenter study. Endoscopy 39:793–801

    Article  CAS  PubMed  Google Scholar 

  27. Masci E, Mariani A, Curioni S, Curioni S, Testoni PA (2003) Risk factors for pancreatitis following endoscopic retrograde cholangiopancreatography: a meta-analysis. Endoscopy 35:830–834

    Article  CAS  PubMed  Google Scholar 

  28. Freeman ML, DiSario JA, Nelson DB, Fennerty MD, Lee JG, Bjorkman DJ, Overby CS, Aas J, Ryan ME, Bochna GS, Shaw MJ, Snady HW, Erickson RV, Moore JP, Roel JP (2001) Risk factors for post-ERCP pancreatitis: a prospective, multicenter study. Gastrointest Endosc 54:425–434

    Article  CAS  PubMed  Google Scholar 

  29. Masci E, Toti G, Mariani A, Curioni S, Lomazzi A, Dinelli M, Minoli G, Crosta C, Comin U, Fertitta A, Prada A, Passoni GR, Testoni PA (2001) Complications of diagnostic and therapeutic ERCP: a prospective multicenter study. Am J Gastroenterol 96:417–423

    Article  CAS  PubMed  Google Scholar 

  30. Herreros de Tejada A, Calleja JL, Díaz G, Pertejo V, Espinel J, Cacho G, Jiménez J, Millán I, García F, Abreu L, UDOGUIA-04 Group (2009) Double-guidewire technique for difficult bile duct cannulation: a multicenter randomized, controlled trial. Gastrointest Endosc 70:700–709

    Article  PubMed  Google Scholar 

  31. Wang P, Zhang W, Liu F, Zs Li, Ren X, Fan ZN, Zhang X, Lu NH, Sun WS, Shi RH, Li YQ, Zhao Q (2010) Success and complication rates of two precut techniques, transpancreatic sphincterotomy and needle-knife sphincterotomy for bile duct cannulation. J Gastrointest Surg 14:697–704

    Article  PubMed  Google Scholar 

  32. Halttunen J, Keränen I, Udd M, Kylänpää L (2009) Pancreatic sphincterotomy versus needle knife precut in difficult biliary cannulation. Surg Endosc 23:745–749

    Article  PubMed  Google Scholar 

  33. Weber A, Roesch T, Pointner S, Born P, Neu B, Meining A, Schmid RM, Prinz C (2008) Transpancreatic precut sphincterotomy for cannulation of inaccessible common bile duct: a safe and successful technique. Pancreas 36:187–191

    Article  PubMed  Google Scholar 

  34. Yoo YW, Cha SW, Lee WC, Kim SH, Kim A, Cho YD (2013) Double guidewire technique vs transpancreatic precut sphincterotomy in difficult biliary cannulation. World J Gastroenterol 19:108–114

    Article  PubMed  PubMed Central  Google Scholar 

  35. Miao L, Li Q, Zhu M, Ge XX, Yu H, Wang F, Ji GZ (2015) Endoscopic transpancreatic septotomy as a precutting technique for difficult bile duct cannulation. World J Gastroenterol 21:3978–3982

    Article  PubMed  PubMed Central  Google Scholar 

  36. Yaghoobi M, Rolland S, Waschke KA, McNabb-Baltar J, Martel M, Bijarchi R, Szego P, Barkun AN (2013) Meta-analysis: rectal indomethacin for the prevention of post-ERCP pancreatitis. Aliment Pharmacol Ther 38:995–1001

    Article  CAS  PubMed  Google Scholar 

  37. Yuhara H, Ogawa M, Kawaguchi Y, Igarashi M, Shimosegawa T, Mine T (2014) Pharmacologic prophylaxis of post-endoscopic retrograde cholangiopancreatography pancreatitis: protease inhibitors and NSAIDs in a meta-analysis. J Gastroenterol 49:388–399

    Article  CAS  PubMed  Google Scholar 

  38. Sethi S, Sethi N, Wadhwa V, Garud S, Brown A (2014) A meta-analysis on the role of rectal diclofenac and indomethacin in the prevention of post-endoscopic retrograde cholangiopancreatography pancreatitis. Pancreas 43:190–197

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Gastroenterology and Hepatology, Santa Casa Hospital/Federal University of Health Sciences of Porto Alegre (UFCSPA), Rua São Francisco, 469/1203, Porto Alegre, 90620-070, Brazil

    Fernanda de Quadros Onófrio, Julio Carlos Pereira Lima, Daniela Oba & Gabriela Camargo

  2. The Post-Graduation Program in Chest Medicine Sciences, Santa Casa Hospital, Porto Alegre, Brazil

    Guilherme Watte

  3. Department of Anesthesiology, Santa Casa Hospital, Porto Alegre, Brazil

    Romnei Lenon Lehmen

  4. Department of Gastroenterology and Endoscopy, Santa Casa de Caridade de Bagé, Bagé, Brazil

    Carlos Eduardo Oliveira dos Santos

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  1. Fernanda de Quadros Onófrio
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Correspondence to Fernanda de Quadros Onófrio.

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Disclosures

Dr. Julio Carlos Pereira Lima (jpereiralima@terra.com.br) is on the speakers’ board of Takeda Pharmaceutical and receives honoraria as consultant of Boston Scientific. The patients’ private or public health insurance funded all ERCPs including the drugs used in this trial. Drs. Fernanda de Quadros Onófrio (fqonofrio@gmail.com), Guilherme Watte (g.watte@gmail.com), Romnei Lenon Lehmen (lenon@mail.com), Daniela Oba (oba.daniela@gmail.com), Gabriela Camargo (camargo.gabriela@gmail.com) and Carlos Eduardo Oliveira dos Santos (ddendo@uol.com.br) have no conflicts of interest or financial ties to disclose.

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de Quadros Onófrio, F., Lima, J.C.P., Watte, G. et al. Prophylaxis of pancreatitis with intravenous ketoprofen in a consecutive population of ERCP patients: a randomized double-blind placebo-controlled trial. Surg Endosc 31, 2317–2324 (2017). https://doi.org/10.1007/s00464-016-5234-x

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