Rectal Indomethacin and Spraying of Duodenal Papilla With Epinephrine Increases Risk of Pancreatitis Following Endoscopic Retrograde Cholangiopancreatography

Clin Gastroenterol Hepatol. 2019 Jul;17(8):1597-1606.e5. doi: 10.1016/j.cgh.2018.10.043. Epub 2018 Oct 31.

Abstract

Background & aims: Rectal indomethacin and spraying of the duodenal papilla with epinephrine might reduce the incidence of pancreatitis after endoscopic retrograde cholangiopancreatography (ERCP). We performed a randomized trial to compare the effects of the combination of indomethacin and epinephrine (IE) vs indomethacin plus saline (IS) in prophylaxis of post-ERCP pancreatitis (PEP).

Methods: We performed a double-blind trial at 10 centers in China, from February 2017 to October 2017, of 1158 patients with native papilla undergoing ERCP. The patients were assigned randomly to groups given IE (n = 576) or IS (n = 582). All patients received a single dose of rectal indomethacin within 30 minutes before ERCP; 20 mL of dilute epinephrine (IE group) or saline (IS group) then was sprayed on the duodenal papilla at the end of ERCP. The primary outcome was the incidence of overall PEP. Data were analyzed on an intention-to-treat principle.

Results: The study was terminated at the interim analysis for safety concerns and futility. The groups had similar baseline characteristics. PEP developed in 49 patients in the IE group (8.5%) and in 31 patients in the IS group (5.3%) (relative risk, 1.60, 95% CI, 1.03-2.47; P = .033). There were no significant differences between groups in proportions of patients with postsphincterotomy bleeding (2.1% in the IE group and 1.5% in the IS group) and biliary infection (1.2% in the IE group and 2.2% in the IS group).

Conclusions: In a randomized trial, we found the combination of rectal indomethacin with papillary epinephrine spraying increased the risk of PEP compared with indomethacin alone. Spray epinephrine should not be used with rectal indomethacin for prevention of post-ERCP pancreatitis. ClincialTrials.gov no: NCT03057769.

Keywords: Anti-Inflammatory; Chemoprophylaxis; NSAIDs; Prevention.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Rectal
  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Ampulla of Vater
  • China / epidemiology
  • Cholangiopancreatography, Endoscopic Retrograde / adverse effects*
  • Double-Blind Method
  • Drug Therapy, Combination
  • Epinephrine / administration & dosage*
  • Epinephrine / adverse effects
  • Female
  • Follow-Up Studies
  • Humans
  • Incidence
  • Indomethacin / administration & dosage*
  • Indomethacin / adverse effects
  • Male
  • Middle Aged
  • Pancreatitis / diagnosis
  • Pancreatitis / epidemiology
  • Pancreatitis / etiology*
  • Retrospective Studies
  • Risk Assessment / methods*
  • Risk Factors
  • Therapeutic Irrigation / adverse effects
  • Young Adult

Substances

  • Indomethacin
  • Epinephrine

Associated data

  • ClinicalTrials.gov/NCT03057769