A Randomized Trial of Topical Epinephrine and Rectal Indomethacin for Preventing Post-Endoscopic Retrograde Cholangiopancreatography Pancreatitis in High-Risk Patients

Abstract

INTRODUCTION: Rectal indomethacin and topical spray of epinephrine have separately shown efficacy in the prevention of post-endoscopic retrograde cholangiopancreatography pancreatitis (PEP) in randomized controlled trials. We hypothesized that the combination of indomethacin and topical spray of epinephrine on the duodenal papillae would further reduce PEP than when indomethacin was used alone. Methods: We conducted a comparative effectiveness, multicenter, double-blinded, randomized trial of rectal indomethacin alone vs a combination of rectal indomethacin and topical spray of epinephrine for the prevention of PEP in high-risk patients. The primary outcome was the incidence of PEP and the secondary outcome was the severity of PEP. A 2-tailed Fisher's exact test was used to analyze the difference in the proportion of patients with PEP in the indomethacin alone vs the combination group. Results: A total of 960 patients (mean age 52.33 ± 14.96 years; 551 [57.4%] females) were randomized and 959 completed follow-up. The baseline demographic and clinical characteristics were similar between the 2 groups. Women <50 years of age (25.4%) and difficult cannulation (84.9%) were the most common PEP risk factors. The incidence of PEP was 6.4% in the indomethacin alone group (n = 482) compared to 6.7% in the combination group (n = 477; P = 0.87). Severe PEP was found in 5 (12%) and 7 (16%) patients in the indomethacin alone and combination groups, respectively (P = 0.88). The overall mortality was 0.6%, which was unrelated to the primary outcome. Conclusions: The combination of rectal indomethacin and topical spray of epinephrine does not reduce the incidence of PEP compared to rectal indomethacin alone in high-risk patients; https://clinicaltrials.gov/ct2/show/NCT02116309.

Fluid type and volume reduce risk of post-ERCP pancreatitis and length of hospital stay in high-risk patients: a secondary analysis of the INDIEH trial

“…The current study is a secondary analysis of a prospective multicenter, double blinded, randomized trial in high risk patients comparing the efficacy of rectal indomethacin versus a combination of topical spray of epinephrine and rectal indomethacin for the prevention of PEP in high-risk patients (INDIEH trial) [10]. The trial was conducted at four tertiary care teaching hospitals, the Johns Hopkins Medical Institutions (United States), Asian Institute of Gastroenterology (India), Postgraduate Institute of Medical Education & Research (India) and Apollo Gleneagles Hospital (India).…”

“…The primary aim of the current study was to evaluate the impact of type and volume of intravenous (IV) fluid administered on the incidence of PEP in high-risk patients through a secondary analysis of the INDIEH trial [10]. The secondary aim was to determine if the type and volume of IV fluid administered reduced the length of hospital stay.…”

Positive correlation between pancreatic volume and post‐endoscopic retrograde cholangiopancreatography pancreatitis

“…The inclusion criteria were age > 20 years and initial image recordings of ERCP. The exclusion criteria were as follows: (i) enteroscopy‐assisted ERCP (postoperative cases; Billroth II gastrectomy, Roux‐en‐Y bypass), (ii) not naïve papilla (ERCP for biliary stent removal or exchange without anticipated pancreatogram, and subject with prior biliary sphincterotomy now scheduled for repeat biliary therapy without anticipated pancreatogram), (iii) pancreatic cancer cases, (iv) pancreatic cystic neoplasm cases, (v) findings of CP or fatty replacement of the pancreas on computerized tomography (CT) (i.e. evidence of CP with pancreatic calculi and multiple or diffuse calcifications distributed in the pancreas, a case in which fatty replacement is strong and pancreatic volume could not be measured), (vi) pre‐ERCP image is magnetic resonance imaging only case, and (vii) pancreatic stenting case.…”

Post-endoscopic retrograde cholangiopancreatography pancreatitis prevention using topical epinephrine: systematic review and meta-analysis

“…Initial search revealed 109 articles, of which eight studies, including six RCTs and two observational studies with 4123 patients were included in this systematic review and meta-analysis [19][20][21][25][26][27][28][29]. ▶ Fig.…”

“…Evidence regarding use of topical epinephrine in prevention of PEP is inconsistent, with some studies favoring their use while other studies did not show any benefit. Compounding this question is concurrent use of topical epinephrine with rectal NSAIDS [19][20][21]. We, therefore, conducted a systematic review and meta-analysis to delineate if topical epinephrine is useful in the prevention of PEP.…”