Background

Non-steroidal anti-inflammatory drugs (NSAIDs), intravenous fluid, pancreatic stents, or combinations of these have been evaluated in randomised controlled trials (RCTs) for the prevention of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis, but the comparative efficacy of these treatments remains unclear. Our aim was to do an exploratory network meta-analysis of previous RCTs to systematically compare the direct and indirect evidence and rank NSAIDs, intravenous fluids, pancreatic stents, or combinations of these to determine the most efficacious method of prophylaxis for post-ERCP pancreatitis.

Methods

We searched PubMed, Embase, and the Cochrane Central Register from inception to Nov 15, 2020, for full-text RCTs that evaluated the efficacy of NSAIDs, pancreatic stents, intravenous fluids, or combinations of these for post-ERCP pancreatitis prevention in adult (aged ≥18 years) patients undergoing ERCP. Summary data from intention-to-treat analyses were extracted from published reports. We analysed incidence of post-ERCP pancreatitis across studies using network meta-analysis under the frequentist framework, obtaining pairwise odds ratios (ORs) and 95% CIs. We used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system for the confidence rating. This study is registered with PROSPERO, CRD42020172606.

Findings

We identified 1503 studies, of which 55 RCTs evaluating 20 interventions in 17 062 patients were included in the network meta-analysis. The mean incidence of post-ERCP pancreatitis in the placebo or active control group was 12·2% (95% CI 11·4–13·0). Normal saline plus rectal indometacin (OR 0·02, 95% CI 0·00–0·40), intramuscular diclofenac 75 mg (0·24, 0·09–0·69), intravenous high-volume Ringer's lactate plus rectal diclofenac 100 mg (0·30, 0·16–0·55), intravenous high-volume Ringer's lactate (0·31, 0·12–0·78), 5–7 Fr pancreatic stents (0·35, 0·26–0·48), rectal diclofenac 100 mg (0·36, 0·25–0·52), 3 Fr pancreatic stents (0·47, 0·26–0·87), and rectal indometacin 100 mg (0·60, 0·50–0·73) were all more efficacious than placebo for preventing post-ERCP pancreatitis in pairwise comparisons. 5–7 Fr pancreatic stents (0·59, 0·41–0·84), intravenous high-volume Ringer's lactate plus rectal diclofenac 100 mg (0·49, 0·26–0·94), intravenous standard-volume normal saline plus rectal indometacin 100 mg (0·04, 0·00–0·66), and rectal diclofenac 100 mg (0·59, 0·40–0·89) were more efficacious than rectal indometacin 100 mg. The GRADE confidence rating was low to moderate for 98·3% of the pairwise comparisons.

Interpretation

This systematic review and network meta-analysis summarises the available literature on NSAIDs, pancreatic stents, intravenous fluids, or combinations of these for prophylaxis of post-ERCP pancreatitis. Rectal diclofenac 100 mg is the best performing rectal NSAID in this network meta-analysis. Combinations of prophylaxis might be more effective, but there is little evidence. These findings help to establish prophylaxis of post-ERCP pancreatitis for future research and practice, and could reduce costs and increase adoption of prophylaxis.

Funding

None.

中文翻译：

---

非甾体抗炎药、静脉输液、胰腺支架或其组合预防内镜逆行胰胆管造影术后胰腺炎：系统评价和网络荟萃分析

背景

非甾体抗炎药 (NSAID)、静脉输液、胰腺支架或这些药物的组合已在随机对照试验 (RCT) 中评估用于预防内窥镜逆行胰胆管造影 (ERCP) 术后胰腺炎，但这些治疗尚不清楚。我们的目的是对先前的 RCT 进行探索性网络荟萃分析，以系统地比较直接和间接证据，并对 NSAID、静脉输液、胰腺支架或这些的组合进行排名，以确定最有效的 ERCP 后胰腺炎预防方法。

方法

我们在 PubMed、Embase 和 Cochrane Central Register 从开始到 2020 年 11 月 15 日期间搜索了全文 RCT，这些 RCT 评估了 NSAID、胰腺支架、静脉输液或这些药物的组合对成人 ERCP 后胰腺炎预防的疗效（年龄≥18 岁）接受 ERCP 的患者。从已发表的报告中提取了意向治疗分析的汇总数据。我们在频率论框架下使用网络荟萃分析分析了跨研究的 ERCP 后胰腺炎的发生率，获得了成对优势比 (OR) 和 95% CI。我们使用了建议评估、开发和评估分级 (GRADE) 系统进行置信度评级。本研究已在 PROSPERO 注册，CRD42020172606。

发现

我们确定了 1503 项研究，其中 55 项 RCT 评估了 17 062 名患者的 20 项干预措施，被纳入网络荟萃分析。安慰剂组或活性对照组中 ERCP 后胰腺炎的平均发生率为 12·2% (95% CI 11·4–13·0)。生理盐水加直肠吲哚美辛（OR 0·02，95% CI 0·00-0·40），肌注双氯芬酸 75 mg（0·24，0·09-0·69），静脉注射大容量乳酸林格氏液加直肠双氯芬酸100 mg (0·30, 0·16–0·55), 静脉注射高容量乳酸林格氏液 (0·31, 0·12-0·78), 5-7 Fr 胰腺支架 (0·35, 0·26 –0·48)、直肠双氯芬酸 100 mg (0·36, 0·25-0·52)、3 Fr 胰腺支架 (0·47, 0·26-0·87) 和直肠吲哚美辛 100 mg (0· 60, 0·50–0·73) 在成对比较中都比安慰剂更有效地预防 ERCP 后胰腺炎。5-7 Fr 胰腺支架 (0·59, 0·41-0·84), 静脉注射高容量乳酸林格氏液加直肠双氯芬酸 100 mg (0·49, 0·26–0·94)，静脉注射标准容量生理盐水加直肠吲哚美辛 100 mg (0·04, 0·00–0·66)，和直肠双氯芬酸 100 mg (0·59, 0·40–0·89) 比直肠 100 mg 吲哚美辛更有效。98·3% 的成对比较的 GRADE 置信等级为低到中等。

解释

本系统评价和网络荟萃分析总结了关于 NSAID、胰腺支架、静脉输液或这些药物组合用于预防 ERCP 后胰腺炎的现有文献。在该网络荟萃分析中，直肠双氯芬酸 100 mg 是表现最佳的直肠 NSAID。预防的组合可能更有效，但几乎没有证据。这些发现有助于为未来的研究和实践建立 ERCP 后胰腺炎的预防措施，并可以降低成本并增加预防措施的采用。

资金

没有任何。