Aggressive fluid hydration plus non-steroidal anti-inflammatory drugs versus non-steroidal anti-inflammatory drugs alone for post-endoscopic retrograde cholangiopancreatography pancreatitis (FLUYT): a multicentre, open-label, randomised, controlled trial

Christina Weiland ,Wim Van De Vrie,Nora D L Hallensleben,David W Da Costa,Harry Van Goor,Devica S Umans,Abha Bhalla,Paul Fockens,Muhammed Hadithi,Erwin J M Van Geenen,Wietske Kievit,Xavier J N M Smeets,Peter Van Der Schaar,Jan Maarten Vrolijk,Tessa E H Römkens,Brechje C Van Eijck,Thomas R De Wijkerslooth ,Tom Seerden ,Marco J Bruno ,Matthijs P Schwartz ,Marc G Besselink ,Yolande C.a Keulemans ,Hjalmar C Van Santvoort ,Joost P.h Drenth ,R Weiland ,Alexander C Poen ,Sven M Van Dijk ,W J Thijs ,Niels G Venneman ,Jeanin E Van Hooft ,Ben J.m Witteman ,Roy L Van Wanrooij ,Hester C Timmerhuis ,Robert C Verdonk ,Adriaan C Tan ,A Voorburg ,Lubbertus C Baak

doi:10.1016/s2468-1253(21)00057-1

Abstract

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. 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. 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). 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. Netherlands Organisation for Health Research and Development and Radboud University Medical Center.

Highlights

In the USA alone, 169 510 endoscopic retrograde cholangiopancreatographies (ERCPs) are done annually.[1]
We did a systemic review before trial commencement using PubMed and Embase to search for research articles published in English up to Feb 17, 2016, with the following search terms: (“cholangiopancreatography, endoscopic retrograde”, “ERCP”) and (“fluid therap*”, “fluid administrat*”, “fluid volume”, “intravenous infusion”, “rehydrate”, or “hydrat*”)
On the basis of this systematic review, there was evidence to suggest that periprocedural hydration affords protection against post-ERCP pancreatitis

Summary

Introduction

In the USA alone, 169 510 endoscopic retrograde cholangiopancreatographies (ERCPs) are done annually.[1] Pancreatitis is the most common complication of ERCP, with an incidence of up to 14·7% in patients at high risk.[2] Post-ERCP pancreatitis can progress to moderate or severe pancreatitis in 4·7% of patients and is associated with an overall mortality rate of 0·7%.2,3 www.thelancet.com/gastrohep Vol 6 May 2021. Evidence before this study Pancreatitis is the most common complication of endoscopic retrograde cholangiopancreatography (ERCP). Evidence has emerged that aggressive periprocedural hydration using Ringer’s lactate solution is effective in reducing post-ERCP pancreatitis. On the basis of this systematic review, there was evidence to suggest that periprocedural hydration affords protection against post-ERCP pancreatitis. The included studies did not use prophylactic rectal NSAIDs, which are seen as the standard

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