What is the role of indomethacin (Nonsteroidal Anti-Inflammatory Drug, NSAID) in preventing post-Endoscopic Retrograde Cholangiopancreatography (ERCP) pancreatitis?

From the Guidelines

Indomethacin is recommended for the prevention of post-ERCP pancreatitis (PEP) in all patients undergoing ERCP without contraindication, as it has been shown to reduce the risk of PEP. The standard regimen is a single 100 mg rectal suppository administered immediately before or after the ERCP procedure, as recommended by the European Society of Gastrointestinal Endoscopy (ESGE) and European Association for the Study of the Liver (EASL) clinical guideline 1. This approach is supported by high-quality evidence, including meta-analyses that demonstrate the benefit of rectal non-steroidal anti-inflammatory drugs (NSAIDs), such as indomethacin, in preventing PEP 1.

Key Considerations

• The use of indomethacin should be part of a comprehensive approach to PEP prevention, which may also include adequate hydration and minimizing pancreatic duct manipulation during the procedure.
• Contraindications to indomethacin include active peptic ulcer disease, renal impairment (eGFR <30 ml/min), hypersensitivity to NSAIDs, or pregnancy in the third trimester.
• Potential side effects of indomethacin include rectal irritation, gastrointestinal bleeding, and renal dysfunction, although it is generally well-tolerated when given as a single dose.

High-Risk Patients

• Patients with risk factors such as suspected sphincter of Oddi dysfunction, difficult cannulation, pancreatic duct instrumentation, or prior history of PEP may benefit from additional preventive measures, including the placement of a 5-Fr prophylactic pancreatic stent 1.
• The use of pancreatic stents in addition to rectal NSAIDs may be considered in high-risk patients, although the additive benefit is uncertain 1.

Clinical Practice

• The ESGE/EASL clinical guideline recommends routine rectal administration of 100 mg of diclofenac or indomethacin immediately before or after ERCP in all patients without contraindication 1.
• The use of indomethacin for PEP prevention is supported by recent studies, including a Cochrane analysis that compared the contrast-assisted with the guidewire-assisted cannulation technique and showed that the guidewire technique reduced the risk of PEP 1.

From the Research

Role of Indomethacin in Preventing Post-ERCP Pancreatitis

• Indomethacin, a Nonsteroidal Anti-Inflammatory Drug (NSAID), has been shown to reduce the incidence of post-Endoscopic Retrograde Cholangiopancreatography (ERCP) pancreatitis 2, 3, 4.
• A randomized trial found that rectal indomethacin significantly reduced the incidence of post-ERCP pancreatitis, with a decrease from 16.9% in the placebo group to 9.2% in the indomethacin group 2.
• A meta-analysis of four randomized controlled trials confirmed that rectally administered indomethacin decreased the incidence of post-ERCP pancreatitis, with an odds ratio of 0.49 3.
• The use of indomethacin has been shown to be beneficial in both high-risk and low-risk patients undergoing ERCP, including those with malignant biliary obstruction 4.

Comparison with Other Preventive Measures

• A randomized non-inferiority trial found that indomethacin alone was not as effective as the combination of indomethacin and prophylactic pancreatic stent placement in preventing post-ERCP pancreatitis in high-risk patients 5.
• Emerging therapies, such as aggressive hydration with lactated Ringer's and sublingual nitrate, may provide additional benefit to rectal NSAIDs in preventing post-ERCP pancreatitis 6.

Clinical Implications

• Rectal indomethacin is recommended as a preventive measure for post-ERCP pancreatitis, particularly in high-risk patients 2, 3, 4.
• The combination of indomethacin and prophylactic pancreatic stent placement may be considered in high-risk patients, although the use of indomethacin alone may still be beneficial in some cases 5.