Sperna Weiland Christina J, Smeets Xavier J N M, Kievit Wietske, Verdonk Robert C, Poen Alexander C, Bhalla Abha, Venneman Niels G, Witteman Ben J M, da Costa David W, van Eijck Brechje C, Schwartz Matthijs P, Römkens Tessa E H, Vrolijk Jan Maarten, Hadithi Muhammed, Voorburg Annet M C J, Baak Lubbertus C, Thijs Willem J, van Wanrooij Roy L, Tan Adriaan C I T L, Seerden Tom C J, Keulemans Yolande C A, de Wijkerslooth Thomas R, van de Vrie Wim, van der Schaar Peter, van Dijk Sven M, Hallensleben Nora D L, Sperna Weiland Ruud L, Timmerhuis Hester C, Umans Devica S, van Hooft Jeanin E, van Goor Harry, van Santvoort Hjalmar C, Besselink Marc G, Bruno Marco J, Fockens Paul, Drenth Joost P H, van Geenen Erwin J M
Department of Gastroenterology and Hepatology, Radboud University Medical Center, Nijmegen, Netherlands; Department of Research and Development, St Antonius Hospital, Nieuwegein, Netherlands.
Department for Health Evidence, Radboud University Medical Center, Nijmegen, Netherlands.
Lancet Gastroenterol Hepatol. 2021 May;6(5):350-358. doi: 10.1016/S2468-1253(21)00057-1. Epub 2021 Mar 19.
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.
胰腺炎是内镜逆行胰胆管造影术（ERCP）最常见的并发症。预防性直肠给予非甾体类抗炎药（NSAIDs）被视为降低ERCP术后胰腺炎风险的标准治疗方法。有人提出积极补液可能会进一步降低这种风险。尽管这既费力又耗时，但指南已建议对无法接受直肠NSAIDs治疗的患者进行积极补液。我们旨在评估积极补液对接受预防性直肠NSAIDs治疗患者的附加价值。
FLUYT是一项在22家荷兰医院进行的多中心、开放标签、随机对照试验，纳入了年龄在18至85岁之间、发生ERCP术后胰腺炎风险为中度至高风险的患者。患者通过基于网络的模块、采用不同的区组大小，以1:1的比例随机分配至积极补液联合直肠NSAIDs组（100 mg双氯芬酸或吲哚美辛；积极补液组）或仅直肠NSAIDs组（100 mg双氯芬酸或吲哚美辛；对照组）。随机分组根据治疗中心进行分层。积极补液包括在ERCP开始后60分钟内静脉输注20 mL/kg乳酸林格氏液，随后8小时内以每小时3 mL/kg的速度输注。对照组接受静脉输注生理盐水，最大速度为每小时1.5 mL/kg，24小时内总量为3 L。主要终点是ERCP术后胰腺炎，并在改良意向性分析基础上进行分析（包括所有接受随机分组并进行了ERCP且可获得主要结局数据的患者）。该试验已在国际标准随机对照试验编号注册平台注册，编号为ISRCTN13659155。
在2015年6月5日至2019年6月6日期间，826例患者被随机分组，其中388例在积极补液组，425例在对照组被纳入改良意向性分析。积极补液组有30例（8%）患者发生ERCP术后胰腺炎，对照组有39例（9%）患者发生（相对风险0.84，95%置信区间0.53 - 1.33，p = 0.53）。在严重不良事件方面无差异，包括与补液相关的并发症（相对风险0.99，95%置信区间：0.59 - 1.64；p = 1.00）、与ERCP相关的并发症（0.90，0.62 - 1.31；p = 0.62）、入住重症监护病房（0.37，0.07 - 1.80；p = 0.22）以及30天死亡率（0.95，0.50 - 1.83；p = 1.00）。
对于常规接受预防性直肠NSAIDs治疗、发生该并发症风险为中度至高风险的患者，围手术期积极补液并未降低ERCP术后胰腺炎的发生率。因此，为进一步降低ERCP术后胰腺炎风险而进行既费力又耗时的围手术期积极补液的负担是不合理的。
荷兰卫生研究与发展组织和拉德堡德大学医学中心。
