Supplementary Material for: Rectal Indomethacin in Preventing Post-Endoscopic Retrograde Cholangiopancreatography Pancreatitis: An Updated Meta-Analysis with Trial Sequential Analysis

Background: Acute pancreatitis is a significant complication of endoscopic retrograde Cholangiopancreatography (ERCP) with no established prevention strategy. Recent studies suggest that rectal indomethacin may reduce the incidence of post-ERCP pancreatitis (PEP), but its effectiveness varies with patient risk levels and the concurrent use of pancreatic stenting. This updated meta-analysis evaluates the efficacy of rectal indomethacin in preventing PEP. Methods: A systematic search of PubMed, Embase, and Scopus up to April 2025 identified randomized controlled trials (RCTs) comparing rectal indomethacin with placebo for PEP prevention. Random-effects meta-analysis, metaregression, and subgroup analysis were conducted using the R Meta package v8.0- 2. Cochrane's ROB2 and Egger's regression test are used to assess the risk of bias. Results: The analysis included 15 RCTs representing a total of 4962 patients. Rectal indomethacin significantly reduced the incidence of PEP compared to placebo (RR: 0.58; 95% CI, 0.45–0.73; P < 0.01) with no increased risk for bleeding complications (RR: 0.95, 95% CI: 0.64–1.41, P = 0.76). Subgroup analysis showed that indomethacin was effective, especially when given concurrently with a pancreatic stent (RR: 0.4539, 95% CI: 0.26–0.79). However, a high risk of bias was observed in nearly 25% of the overall assessment; there was evidence of a small study effect, as suggested by Egger's regression test (P < 0.01). Conclusion: Prophylactic rectal indomethacin appears to be effective in preventing PEP, with no increased risk for bleeding. Future studies should focus on combining other prophylactic options to achieve better prevention of PEP.

背景：急性胰腺炎是内镜逆行胰胆管造影（Endoscopic Retrograde Cholangiopancreatography，ERCP）的严重并发症，目前尚无公认的预防策略。现有研究表明，直肠给药吲哚美辛可降低ERCP术后胰腺炎（Post-ERCP Pancreatitis，PEP）的发生率，但其疗效会随患者风险等级及同期胰腺支架置入操作的不同而存在差异。本更新版荟萃分析旨在评估直肠吲哚美辛预防PEP的临床疗效。方法：本研究系统性检索了截至2025年4月的PubMed、Embase及Scopus数据库，筛选出对比直肠吲哚美辛与安慰剂预防PEP效果的随机对照试验（Randomized Controlled Trials，RCTs）。采用R语言Meta包v8.0-2开展随机效应模型荟萃分析、元回归及亚组分析；使用Cochrane偏倚风险工具2.0（ROB2）及Egger回归检验评估研究偏倚风险。结果：本次分析共纳入15项RCTs，涉及4962例受试者。与安慰剂组相比，直肠吲哚美辛组的PEP发生率显著降低（相对危险度RR=0.58，95%置信区间CI：0.45~0.73，P<0.01），且未增加出血并发症风险（RR=0.95，95%CI：0.64~1.41，P=0.76）。亚组分析显示，吲哚美辛的预防效果尤为显著，尤其在同期联合胰腺支架置入的亚组中（RR=0.4539，95%CI：0.26~0.79）。不过，近25%的纳入研究存在较高偏倚风险；Egger回归检验结果提示存在小样本效应（P<0.01）。结论：预防性直肠给药吲哚美辛可有效预防PEP，且不会增加出血风险。未来研究应聚焦于联合其他预防方案，以进一步优化PEP的预防效果。