Christina J Sperna Weiland1, Xavier J N M Smeets1, Wietske Kievit2, Robert C Verdonk3, Alexander C Poen4, Abha Bhalla5, Niels G Venneman6, Ben J M Witteman7, David W da Costa8, Brechje C van Eijck9, Matthijs P Schwartz10, Tessa E H Römkens11, Jan Maarten Vrolijk12, Muhammed Hadithi13, Annet M C J Voorburg14, Lubbertus C Baak15, Willem J Thijs16, Roy L van Wanrooij17, Adriaan C I T L Tan18, Tom C J Seerden19, Yolande C A Keulemans20, Thomas R de Wijkerslooth21, Wim van de Vrie22, Peter van der Schaar3, Sven M van Dijk23, Nora D L Hallensleben24, Ruud L Sperna Weiland25, Hester C Timmerhuis26, Devica S Umans27, Jeanin E van Hooft28, Harry van Goor29, Hjalmar C van Santvoort30, Marc G Besselink31, Marco J Bruno32, Paul Fockens17, Joost P H Drenth33, Erwin J M van Geenen34. 1. Department of Gastroenterology and Hepatology, Radboud University Medical Center, Nijmegen, Netherlands; Department of Research and Development, St Antonius Hospital, Nieuwegein, Netherlands. 2. Department for Health Evidence, Radboud University Medical Center, Nijmegen, Netherlands. 3. Department of Gastroenterology and Hepatology, St Antonius Hospital, Nieuwegein, Netherlands. 4. Department of Gastroenterology and Hepatology, Isala Clinics, Zwolle, Netherlands. 5. Department of Gastroenterology and Hepatology, Hagaziekenhuis, The Hague, Netherlands. 6. Department of Gastroenterology and Hepatology, Medisch Spectrum Twente, Enschede, Netherlands. 7. Department of Gastroenterology and Hepatology, Gelderse Vallei Hospital, Ede, Netherlands. 8. Department of Radiology, St Antonius Hospital, Nieuwegein, Netherlands. 9. Department of Gastroenterology and Hepatology, Spaarne Gasthuis, Hoofddorp, Netherlands. 10. Department of Gastroenterology and Hepatology, Meander Medical Centre, Amersfoort, Netherlands. 11. Department of Gastroenterology and Hepatology, Jeroen Bosch Hospital, Den Bosch, Netherlands. 12. Department of Gastroenterology and Hepatology, Rijnstate Hospital, Arnhem, Netherlands. 13. Department of Gastroenterology and Hepatology, Maasstad Hospital, Rotterdam, Netherlands. 14. Department of Gastroenterology and Hepatology, Diakonessenhuis, Utrecht, Netherlands. 15. Department of Gastroenterology and Hepatology, Onze Lieve Vrouwe Gasthuis, Amsterdam, Netherlands. 16. Department of Gastroenterology and Hepatology, Martini Hospital, Groningen, Netherlands. 17. Department of Gastroenterology and Hepatology, Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands. 18. Department of Gastroenterology and Hepatology, Canisius Wilhelmina Hospital, Nijmegen, Netherlands. 19. Department of Gastroenterology and Hepatology, Amphia Hospital, Breda, Netherlands. 20. Department of Gastroenterology and Hepatology, Zuyderland Hospital, Heerlen, Netherlands. 21. Department of Gastroenterology and Hepatology, Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Amsterdam, Netherlands. 22. Department of Gastroenterology and Hepatology, Albert Schweitzer Hospital, Dordrecht, Netherlands. 23. Department of Research and Development, St Antonius Hospital, Nieuwegein, Netherlands; Department of Surgery, Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands. 24. Department of Research and Development, St Antonius Hospital, Nieuwegein, Netherlands; Department of Anaesthesiology, Erasmus Medical Centre, Rotterdam, Netherlands. 25. Institute for Environmental Studies, Vrije Universiteit, Amsterdam, Netherlands. 26. Department of Research and Development, St Antonius Hospital, Nieuwegein, Netherlands. 27. Department of Research and Development, St Antonius Hospital, Nieuwegein, Netherlands; Department of Gastroenterology and Hepatology, Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands. 28. Department of Gastroenterology and Hepatology, Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands; Department of Gastroenterology and Hepatology, Leiden University Medical Centre, Leiden, Netherlands. 29. Department of Surgery, Radboud University Medical Center, Nijmegen, Netherlands. 30. Department of Surgery, St Antonius Hospital, Nieuwegein, Netherlands; Department of Surgery, University Medical Centre Utrecht, Utrecht, Netherlands. 31. Department of Surgery, Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands. 32. Department of Gastroenterology and Hepatology, Erasmus Medical Centre, Rotterdam, Netherlands. 33. Department of Gastroenterology and Hepatology, Radboud University Medical Center, Nijmegen, Netherlands. 34. Department of Gastroenterology and Hepatology, Radboud University Medical Center, Nijmegen, Netherlands. Electronic address: erwin.vangeenen@radboudumc.nl.
Abstract
BACKGROUND: Pancreatitis is the most common complication of endoscopic retrograde cholangiopancreatography (ERCP). Prophylactic rectal administration of non-steroidal anti-inflammatory drugs (NSAIDs) is considered as standard of care to reduce the risk of post-ERCP pancreatitis. It has been suggested that aggressive hydration might further reduce this risk. Guidelines already recommend aggressive hydration in patients who are unable to receive rectal NSAIDs, although it is laborious and time consuming. We aimed to evaluate the added value of aggressive hydration in patients receiving prophylactic rectal NSAIDs. METHODS: FLUYT, a multicentre, open-label, randomised, controlled trial done across 22 Dutch hospitals, included patients aged between 18 and 85 years with moderate to high risk of post-ERCP pancreatitis. Patients were randomly assigned (1:1) by a web-based module with varying block sizes to a combination of aggressive hydration and rectal NSAIDs (100 mg diclofenac or indomethacin; aggressive hydration group) or rectal NSAIDs (100 mg diclofenac or indomethacin) alone (control group). Randomisation was stratified according to treatment centre. Aggressive hydration comprised 20 mL/kg intravenous Ringer's lactate solution within 60 min from the start of ERCP, followed by 3 mL/kg per h for 8 h. The control group received normal intravenous saline with a maximum of 1·5 mL/kg per h and 3 L per 24 h. The primary endpoint was post-ERCP pancreatitis and was analysed on a modified intention-to-treat basis (including all patients who underwent randomisation and an ERCP and for whom data regarding the primary outcome were available). The trial is registered with the ISRCTN registry, ISRCTN13659155. FINDINGS:Between June 5, 2015, and June 6, 2019, 826 patients were randomly assigned, of whom 388 in the aggressive hydration group and 425 in the control group were included in the modified intention-to-treat analysis. Post-ERCP pancreatitis occurred in 30 (8%) patients in the aggressive hydration group and in 39 (9%) patients in the control group (relative risk 0·84, 95% CI 0·53-1·33, p=0·53). There were no differences in serious adverse events, including hydration-related complications (relative risk 0·99, 95% CI 0·59-1·64; p=1·00), ERCP-related complications (0·90, 0·62-1·31; p=0·62), intensive care unit admission (0·37, 0·07-1·80; p=0·22), and 30-day mortality (0·95, 0·50-1·83; p=1·00). INTERPRETATION: Aggressive periprocedural hydration did not reduce the incidence of post-ERCP pancreatitis in patients with moderate to high risk of developing this complication who routinely received prophylactic rectal NSAIDs. Therefore, the burden of laborious and time-consuming aggressive periprocedural hydration to further reduce the risk of post-ERCP pancreatitis is not justified. FUNDING: Netherlands Organisation for Health Research and Development and Radboud University Medical Center.
RCT Entities:
BACKGROUND:Pancreatitis is the most common complication of endoscopic retrograde cholangiopancreatography (ERCP). Prophylactic rectal administration of non-steroidal anti-inflammatory drugs (NSAIDs) is considered as standard of care to reduce the risk of post-ERCP pancreatitis. It has been suggested that aggressive hydration might further reduce this risk. Guidelines already recommend aggressive hydration in patients who are unable to receive rectal NSAIDs, although it is laborious and time consuming. We aimed to evaluate the added value of aggressive hydration in patients receiving prophylactic rectal NSAIDs. METHODS: FLUYT, a multicentre, open-label, randomised, controlled trial done across 22 Dutch hospitals, included patients aged between 18 and 85 years with moderate to high risk of post-ERCP pancreatitis. Patients were randomly assigned (1:1) by a web-based module with varying block sizes to a combination of aggressive hydration and rectal NSAIDs (100 mg diclofenac or indomethacin; aggressive hydration group) or rectal NSAIDs (100 mg diclofenac or indomethacin) alone (control group). Randomisation was stratified according to treatment centre. Aggressive hydration comprised 20 mL/kg intravenous Ringer's lactate solution within 60 min from the start of ERCP, followed by 3 mL/kg per h for 8 h. The control group received normal intravenous saline with a maximum of 1·5 mL/kg per h and 3 L per 24 h. The primary endpoint was post-ERCP pancreatitis and was analysed on a modified intention-to-treat basis (including all patients who underwent randomisation and an ERCP and for whom data regarding the primary outcome were available). The trial is registered with the ISRCTN registry, ISRCTN13659155. FINDINGS: Between June 5, 2015, and June 6, 2019, 826 patients were randomly assigned, of whom 388 in the aggressive hydration group and 425 in the control group were included in the modified intention-to-treat analysis. Post-ERCP pancreatitis occurred in 30 (8%) patients in the aggressive hydration group and in 39 (9%) patients in the control group (relative risk 0·84, 95% CI 0·53-1·33, p=0·53). There were no differences in serious adverse events, including hydration-related complications (relative risk 0·99, 95% CI 0·59-1·64; p=1·00), ERCP-related complications (0·90, 0·62-1·31; p=0·62), intensive care unit admission (0·37, 0·07-1·80; p=0·22), and 30-day mortality (0·95, 0·50-1·83; p=1·00). INTERPRETATION: Aggressive periprocedural hydration did not reduce the incidence of post-ERCP pancreatitis in patients with moderate to high risk of developing this complication who routinely received prophylactic rectal NSAIDs. Therefore, the burden of laborious and time-consuming aggressive periprocedural hydration to further reduce the risk of post-ERCP pancreatitis is not justified. FUNDING: Netherlands Organisation for Health Research and Development and Radboud University Medical Center.
Authors: Christina J Sperna Weiland; Xavier J N M Smeets; Robert C Verdonk; Alexander C Poen; Abha Bhalla; Niels G Venneman; Wietske Kievit; Hester C Timmerhuis; Devica S Umans; Jeanin E van Hooft; Marc G Besselink; Hjalmar C van Santvoort; Paul Fockens; Marco J Bruno; Joost P H Drenth; Erwin J M van Geenen Journal: Endosc Int Open Date: 2022-03-14
Authors: Christina J Sperna Weiland; Celine B E Busch; Abha Bhalla; Marco J Bruno; Paul Fockens; Jeanin E van Hooft; Alexander C Poen; Hester C Timmerhuis; Devica S Umans; Niels G Venneman; Robert C Verdonk; Joost P H Drenth; Thomas R de Wijkerslooth; Erwin J M van Geenen Journal: J Hepatobiliary Pancreat Sci Date: 2021-12-21 Impact factor: 3.149