Pre-procedural indometacin prevents post-ERCP pancreatitis

Last Updated: 2016-05-06

By Will Boggs MD

NEW YORK (Reuters Health) - Pre-procedural rectal indometacin prevents pancreatitis in patients undergoing endoscopic retrograde cholangiopancreatography (ERCP), researchers from China report.

European and Japanese guidelines recommend routine rectal administration of indometacin to prevent post-ERCP pancreatitis, but it has been unclear whether the prophylactic use of rectal indometacin in unselected patients is a better strategy than administration only in high-risk patients.

Dr. Yanglin Pan and Dr. Xuegang Guo, from Fourth Military Medical University, Xi'an, China, and colleagues addressed this issue in a prospective, randomized controlled trial of 2,600 patients undergoing diagnostic or therapeutic ERCP at one of six tertiary referral hospitals.

All 1,297 patients assigned to the "universal" group received a single dose of rectal indometacin within 30 minutes before ERCP. In the risk-stratified group (1,303 patients), only high-risk patients received rectal indometacin immediately following ERCP; average-risk patients did not receive indometacin.

Overall, 4% of patients who received universal pre-procedural indometacin developed post-ERCP pancreatitis, compared with 8% of patients in the risk-stratified post-procedural indometacin group, according to the April 28 online report in the Lancet.

In the subgroup of patients at high risk for post-ERCP pancreatitis, the frequency of post-ERCP pancreatitis was lower among those who received universal prophylaxis (6%) than among those assigned to the risk-stratified group (12%).

Similarly, post-ERCP pancreatitis occurred in 3% of average-risk patients in the universal indometacin group, compared with 6% of average-risk patients in the risk-stratified indometacin group.

The treatment groups did not differ significantly in the rates of gastrointestinal bleeding, biliary infection, or other complications.

"This large-scale study provides direct evidence to support the recommendation that routine rectal administration of (nonsteroidal anti-inflammatory drugs) NSAIDs should be given in all patients without contraindications, published in the European Society of Gastrointestinal Endoscopy and Japanese Society of Hepato-Biliary-Pancreatic Surgery guidelines to prevent post-ERCP pancreatitis," the researchers concluded. "Furthermore, our study findings suggest that rectal indometacin should be administrated before ERCP instead of after ERCP."

"Although most data support a benefit of indometacin for prophylaxis of post-ERCP pancreatitis, differences in patient selection and endoscopic interventions could explain some of the discrepancy between different studies," wrote Dr. Charles de Mestral from the University of Toronto, Toronto General Hospital, Ontario, Canada, in an accompanying editorial. "For example, findings from two recent trials showed no benefit for peri-procedural indometacin compared with placebo."

"Going forward," he wrote, "further investigations should seek to clarify the external validity of the results presented in this trial, particularly because more than 50% of patients were excluded before randomization."

Dr. Martin L. Freeman from the University of Minnesota, Minneapolis, told Reuters Health by email, "The most proven technique for prevention of post-ERCP pancreatitis (PEP) in high-risk and mixed-risk patients is placement of a small caliber pancreatic stent, especially if the pancreatic duct is instrumented with a guidewire in a higher risk patient. There are at least 15 trials and multiple meta-analyses that pancreatic stents reduce risk of PEP by 60-80%. However, enthusiasm for such a technique has been tempered by difficulties and failures. These limitations can be overcome by learning advanced techniques for pancreatic stent placement using very small caliber guidewires in all types of anatomy."

Dr. B. Joseph Elmunzer from Medical University of South Carolina, Charleston, told Reuters Health by email, "The role of indometacin in average-risk cases has been controversial despite guideline recommendations by the European Society of Gastrointestinal Endoscopy for routine administration. This study underscores that administering rectal indometacin (or diclofenac) to all patients at risk for post-ERCP pancreatitis is reasonable and evidence-based."

"Any patient without a contraindication to NSAIDs who is at any risk for post-ERCP pancreatitis should receive rectal indometacin (or diclofenac)," he said. "This study suggests that it should be given pre-procedurally, although many experts administer it at the time of cannulation so that too much time doesn't elapse if the ERCP is delayed (e.g., duodenal stricture that must be treated first)."

"There was no placebo or blinding of the 'no indometacin' group (low-risk, post-procedure administration)," Dr. Elmunzer pointed out. "This may have biased the results in favor of the intervention, although masking was maintained in other important ways, mitigating the overall impact of this study design element."

Dr. Pan and Dr. Guo did not respond to a request for comment.

The National Natural Science Foundation of China funded this research. The authors made no disclosures.

SOURCE: http://bit.ly/270OhUv and http://bit.ly/1ZnLtee

Lancet 2016.