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.

中文翻译：

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积极补液加非甾体抗炎药与单独使用非甾体抗炎药治疗内镜逆行胰胆管造影术后胰腺炎 (FLUYT)：一项多中心、开放标签、随机、对照试验

背景

胰腺炎是内窥镜逆行胰胆管造影术（ERCP）最常见的并发症。预防性直肠给药非甾体抗炎药 (NSAIDs) 被认为是降低 ERCP 术后胰腺炎风险的标准护理。有人建议积极补水可能会进一步降低这种风险。指南已经建议无法接受直肠 NSAID 治疗的患者积极补水，尽管这样做既费力又费时。我们旨在评估接受预防性直肠非甾体抗炎药的患者积极补水的附加价值。

方法

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，包括年龄在 18 至 85 岁之间、ERCP 术后胰腺炎中度至高度风险的患者。患者通过具有不同块大小的基于网络的模块随机分配 (1:1) 到积极水化和直肠 NSAIDs（100 毫克双氯芬酸或吲哚美辛；积极水化组）或直肠 NSAIDs（100 毫克双氯芬酸或吲哚美辛）的组合（对照组）。根据治疗中心对随机化进行分层。积极的水合作用包括在 ERCP 开始后 60 分钟内静脉注射 20 毫升/千克乳酸林格氏溶液，然后是每小时 3 毫升/千克，持续 8 小时。对照组给予生理盐水，最大剂量为1·5 mL/kg/h，3 L/24 h。主要终点是 ERCP 后胰腺炎，并在改良的意向治疗基础上进行分析（包括所有接受随机化和 ERCP 且可获得有关主要结果的数据的患者）。该试验已在 ISRCTN 注册中心 ISRCTN13659155 注册。

调查结果

2015年6月5日至2019年6月6日期间，826名患者被随机分配，其中积极补液组388名和对照组425名被纳入改良意向治疗分析。ERCP 术后胰腺炎发生在积极补液组的 30 (8%) 名患者和对照组的 39 (9%) 名患者中（相对风险 0·84，95% CI 0·53–1·33，p=0 ·53)。严重不良事件没有差异，包括水合相关并发症（相对风险 0·99，95% CI 0·59–1·64；p=1·00），ERCP 相关并发症（0·90，0· 62–1·31；p=0·62）、重症监护病房入院（0·37、0·07–1·80；p=0·22）和 30 天死亡率（0·95、0·50 –1·83；p=1·00）。

口译

对于常规接受预防性直肠非甾体抗炎药的中度至高度发生这种并发症的患者，积极的围手术期补液并不能降低 ERCP 术后胰腺炎的发生率。因此，为了进一步降低 ERCP 术后胰腺炎的风险而进行费力且耗时的积极围手术期补液的负担是不合理的。

资金

荷兰卫生研究与发展组织和 Radboud 大学医学中心。