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Three Part Question

In [patients receiving endoscopic retrograde cholangiopancreatography (ERCP)] is [the use of rectal indomethacin beneficial] to [prevent post-ERCP pancreatitis]?

Clinical Scenario

A 55-year-old man presented to the emergency department due to nausea, jaundice, and mild abdominal pain over the right-upper quadrant that had persisted for three days. Lab data showed hyperbilirubinemia and abdominal CT revealed multiple stones in the common bile duct (CBD). ERCP was performed for removal of CBD stones. Both amylase and lipase were elevated the day following ERCP and post-ERCP pancreatitis was diagnosed. As it is a feasible route for a patient treated without oral intake, you wonder if the use of rectal indomethacin would have lowered the occurrence of post-ERCP pancreatitis?

Search Strategy

Medline 1948-July 2011
{(NSAID. mp. OR exp. Anti-Inflammatory Agents, Non-Steroidal OR indomethacin. mp. OR exp. indomethacin) AND [(cholangiopancreatography, endoscopic retrograde. mp. OR exp. Cholangiopancreatography, Endoscopic Retrograde OR ERCP. mp.) AND (exp. pancreatitis OR pancreatitis. mp.)]} limit to English language AND humans. Cochrane Library July 2011: [endoscopic retrograde cholangiopancreatography AND pancreatitis].

Search Outcome

Altogether 24 papers were found, three of which were considered to be original research of high quality (randomised controlled trials) and were relevant to the topic of interest. One of the three papers was published in English and presented the best evidence to answer the clinical question. No additional relevant citations were found in the Cochrane Library.

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Sotoudehmanesh R et al 2007 Iran	490 patients who underwent ERCP randomised to indomethacin or placebo	Randomised double-blind placebo-controlled trial	Incidence rate of post-ERCP pancreatitis	Post-ERCP pancreatitis occurred in 22/442 patients (5.0%). Seven (3.2%) of these patients were in the indomethacin group and 15/221 (6.8%) were in the placebo group (p = 0.06, OR 0.4, 95% CI 0.2% to 1.1%)	Small number of patients

Comment(s)

Acute pancreatitis is the most frequent complication of ERCP. In recent years, attempts at preventing post-ERCP pancreatitis have been carried out through the use of pharmacological prophylaxis. Activation of trypsin in acinar cells and regulation of proinflammatory mediators by cyclo-oxygenase enzymes both play critical roles in the inflammatory cascade of acute pancreatitis, therefore, non-steroidal anti-inflammatory drugs may be suited to interrupt the cascade and may prevent post-ERCP pancreatitis. Several previous studies have reported a significant effect of diclofenac in preventing post-ERCP pancreatitis, but few studies have provided information pertaining to the effect of indomethacin. The result of this search revealed rectal indomethacin may reduce the incidence of post-ERCP pancreatitis, but further studies with more cases are needed to consolidate the conclusion.

Clinical Bottom Line

Rectal indomethacin may prevent post-ERCP pancreatitis, but further studies with more cases are needed to confirm the benefits.

Level of Evidence

Level 1 - Recent well-done systematic review was considered or a study of high quality is available.

References

1. Sotoudehmanesh R, Khatibian M, Kolahdoozan S, et al. Indomethacin May Reduce the Incidence and Severityof Acute Pancreatitis After ERCP Am J Gastroenterol 2007;102:978–983