From the AGA Journals

VIDEO: Rectal indomethacin does not prevent pancreatitis post ERCP

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Rectal indomethacin may still be protective in high-risk patients

Acute pancreatitis is the most common and feared complication of endoscopic retrograde cholangiopancreatography (ERCP). The incidence of post-ERCP pancreatitis is around 10% with a mortality of 0.7% (Gastrointest Endosc. 2015;81:143-9). Recent advances in noninvasive pancreaticobiliary imaging, risk stratification before ERCP, prophylactic pancreatic stent placement, and administration of nonsteroidal anti-inflammatory drugs (NSAIDs) have improved the overall risk benefit ratio of ERCP.

NSAIDs are potent inhibitors of phospholipase A2, cyclooxygenase, and of the activation of platelets and endothelium, all of which play a central role in the pathogenesis of post-ERCP pancreatitis. NSAIDs constitute an attractive option in clinical practice, because they are inexpensive and widely available with a favorable risk profile. A recent multicenter randomized controlled trial (RCT) of 602 patients at high-risk for post-ERCP pancreatitis showed that rectal indomethacin is associated with a 7.7% absolute and a 46% relative risk reduction of post-ERCP pancreatitis (N Engl J Med. 2012;366:1414-22). These findings have been broadly adapted in endoscopic practice in the United States.

Dr. Georgios Papachristou

The presented RCT by Dr. Levenick and his colleagues evaluated the efficacy of rectal indomethacin in preventing post-ERCP pancreatitis among consecutive patients undergoing ERCP in a single U.S. center. This study was a well designed and conducted RCT following the CONSORT guidelines and utilizing an independent data and safety monitoring board.

The authors reported that rectal indomethacin did not result in reduction of post-ERCP pancreatitis (7.2%) when compared with placebo (4.9%). Of importance, 70% of patients included were at average risk for post-ERCP pancreatitis. Furthermore, despite a calculated sample size of 1,398 patients, the study was terminated early after enrolling only 449 patients based on the interim analysis showing futility to reach a statistically different outcome.

This well executed RCT reports no benefit in administering rectal indomethacin in all patients undergoing ERCP. Evidence strongly supports that rectal indomethacin remains an important advancement in preventing post-ERCP pancreatitis. However, its benefit is likely limited to a selected group of patients, those at high-risk for post-ERCP pancreatitis. Further studies are under way to clarify whether rectal indomethacin alone vs. indomethacin plus prophylactic pancreatic stenting is more effective in preventing post-ERCP pancreatitis in high-risk patients.

Dr. Georgios Papachristou is associate professor of medicine at the University of Pittsburgh. He is a consultant for Shire and has received funding from the National Institutes of Health and the VA Health System.



Patients who receive rectal indomethacin after undergoing endoscopic retrograde cholangiopancreatography (ERCP) are not any less likely to develop pancreatitis than individuals who don’t, according to the findings of a recent study published in Gastroenterology (2016 Jan 9. doi: 10.1053/j.gastro.2015.12.018).

“These results are in contrast to recent studies highlighting the benefit of rectal NSAIDS to prevent PEP [post-ECRP pancreatitis] in high-risk patients [and] counter the guidelines espoused by the European Society for Gastrointestinal Endoscopy, which recently recommended giving rectal indomethacin to prevent PEP in all patients undergoing ERCP,” said the study authors, led by Dr. John M. Levenick of Penn State University in Hershey, Pa.


Dr. Levenick and his coinvestigators screened 604 consecutive patients undergoing ERCP, with and without endoscopic ultrasound, at the Dartmouth-Hitchcock Medical Center between March 2013 and December 2014, eventually enrolling and randomizing 449 subjects into two cohorts: one in which subjects were given indomethacin after undergoing ERCP (n = 223), and one in which subjects were simply given a placebo (n = 226). Randomization happened after subjects’ major papilla had been reached, and cannulation attempts were started.

Individuals were excluded if they had active acute pancreatitis or had undergone ERCP to treat or diagnose acute pancreatitis, if they had any contraindications or allergies to NSAIDs, or were younger than 18 years of age, among other factors. The mean age of the indomethacin cohort was 64.9 years, with 118 (52.9%) females; in the placebo cohort, mean age was 64.3 years and 118 (52.2%) were female.

Pancreatitis occurred in 27 subjects overall, 16 (7.2%) of whom were in the indomethacin cohort and the other 11 (4.9%) were on placebo followed ERCP (P = .33). No subjects receiving indomethacin had severe or moderately severe PEP, but one subject had severe PEP and one had moderately severe PEP in the placebo cohort (P = 1.0). There was no necrotizing pancreatitis in either cohort, nor were there any significant differences in gastrointestinal bleeding (P = .75), death (P = .25), or 30-day hospital readmission (P = .1) between the two cohorts.

“Prophylactic rectal indomethacin did not reduce the incidence or severity of PEP in consecutive patients undergoing ERCP,” Dr. Levenick and his coauthors concluded, adding that “guidelines that recommend the administration of rectal indomethacin in all patients undergoing ERCP should be reconsidered.”

This study was funded by the National Pancreas Foundation and a grant from the National Institutes of Health. Dr. Levenick and his coauthors did not report any financial disclosures.

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