Rectal Indomethacin Does Not Prevent Post-ERCP Pancreatitis in Consecutive Patients

Abstract

Background & Aims Rectal indomethacin, a non-steroidal anti-inflammatory drug, is given to prevent pancreatitis in high-risk patients undergoing endoscopic retrograde cholangiopancreatography (ERCP), based on findings from clinical trials. European Society for Gastrointestinal Endoscopy guidelines recently recommended prophylactic rectal indomethacin for all patients undergoing ERCP, including those at average risk for pancreatitis. We performed a randomized controlled trail to investigate the efficacy of this approach. Methods We performed a prospective, double-blind, placebo-controlled trial of 449 consecutive patients undergoing ERCP at Dartmouth Hitchcock Medical Center, from March 2013 through December 2014. Approximately 70% of the cohort were at average-risk for PEP. Subjects were randomly assigned to groups given either a single 100 mg dose of rectal indomethacin (n=223) or a placebo suppository (n=226) during the procedure. The primary outcome was the development of post-ERCP pancreatitis (PEP), defined by new upper-abdominal pain, a level of lipase greater than 3-fold the upper limit of normal, and hospitalization following ERCP for 2 consecutive nights. Results There were no differences between the groups in baseline clinical or procedural characteristics. Sixteen patients in the indomethacin group (7.2%) and 11 in the placebo group (4.9%) developed PEP (P=.33). Complications and the severity of PEP were similar between groups. Per a priori protocol guidelines, the study was stopped due to futility. Conclusions In a randomized controlled study of consecutive patients undergoing ERCP, rectal indomethacin did not prevent post-ERCP pancreatitis. ClincialTrials.gov no: NCT01774604

The incidence of post-ERCP pancreatitis is not reduced in patients given intravenous ketorolac for post-procedural abdominal pain

“…A theoretical advantage of intravenous injection of NSAIDs, compared to the rectal route, could be the complete absorption of the drug; rectal absorption may be incomplete for anatomical reasons and rectal gas expulsion after the procedure because of air insufflation, which could even lead to expulsion of the suppository [22]; both these issues should be overcome by intravenous injection. However, despite recent doubts about usefulness of NSAIDs in preventing PEP [13], rectal but not intravenous NSAIDs seemed to be effective for this purpose, suggesting the importance of the route of administration to prevent this complication. As reported by Sotoudehmanesh et al [23], the plasma half-life of indomethacin administered as a suppository is 4.5 h which should be adequate to influence the initial cellular activation of the pancreatic reaction after ERCP (within an appropriate therapeutic window; it should be adequate when PEP occurs).…”

“…Based on these data recent European guidelines recommend the routine rectal administration of 100 mg of diclofenac or indomethacin in all patients, if there are no contraindications, immediately before or after ERCP to reduce the risk of PEP [8]. However, surprisingly, a recent randomized controlled trial showed that rectal indomethacin was ineffective for PEP prevention [13] suggesting that NSAIDs alone may not be sufficient in chemoprevention of this complication. NSAIDs delivered orally (diclofenac) [14], intramuscularly (diclofenac) [15][16], or intravenously (i.v.…”

Endoscopic retrograde cholangiopancreatography complications: Techniques to reduce risk and management strategies

“…A recent PRCT by Levenick et al 38 reported that RNSAIDs did not protect against PEP in consecutive patients undergoing ERCP, the majority of which were average-risk patients. The overall rates for PEP after placebo (4.9%) were similar to that after RNSAID (7.2%).…”

“…11,13,32,35,36 When pancreatography is completely avoided, PEP should be very uncommon (< 3%). 13,37,38 Reasonable definitions for difficult cannulation range from cannulation attempts for > 5-10 minutes, > 5-15 cannulation attempts, and/or > 1-5 inadvertent pancreatic duct manipulations. 11,29,31 In situations where biliary cannulation is difficult and repeated pancreatic cannulation occurs, some experts advocate a double guidewire technique (DGWT) to increase success.…”

Editorial: Guidewire Trauma: A Key Component of Post-ERCP Pancreatitis That Is Best Controlled by the Endoscopist

“…Of the randomized trials, only one was conducted in the United States ( 14 ) and that trial consisted largely of patients with SOD type III, a now defunct indication for ERCP. However, earlier this year, Levenik et al ( 15 ) published a randomized trial in unselected consecutive ERCP at showing no statistical diff erence in the indomethacin group when compared with placebo.…”