Pharmacological prophylaxis versus pancreatic duct stenting plus pharmacological prophylaxis for prevention of post-ERCP pancreatitis in high risk patients: a randomized trial

Abstract

Background Acute pancreatitis is a serious complication of endoscopic retrograde cholangiopancreatography (ERCP). The aim of this noninferiority study was to evaluate the effectiveness of pancreatic duct (PD) stenting plus pharmacological prophylaxis vs. pharmacological prophylaxis alone in the prevention of post-ERCP pancreatitis (PEP) in high risk patients. Methods In this randomized, controlled, double-blind, noninferiority trial, patients at high risk of developing PEP were randomly allocated to pharmacological prophylaxis (rectal indomethacin, sublingual isosorbide dinitrate, and intravenous hydration with Ringer’s lactate) plus PD stenting (group A) or pharmacological prophylaxis alone (group B). The rate and severity of PEP, serum amylase levels, and length of hospital stay after ERCP were assessed. Results During 21 months, a total of 414 patients (mean age 55.5 ± 17.0 years; 60.2 % female) were enrolled (207 in each group). PEP occurred in 59 patients (14.3 %, 95 % confidence interval [CI] 11.1 % – 17.9 %: 26 patients [12.6 %, 95 %CI 8.6 % – 17.6 %] in group A and 33 [15.9 %, 95 %CI 11.4 % – 21.4 %] in group B). There was no significant difference between the two groups in PEP severity (P = 0.59), amylase levels after 2 hours (P = 0.31) or 24 hours (P = 0.08), and length of hospital stay (P = 0.07). Conclusions The study failed to demonstrate noninferiority or inferiority of pharmacological prophylaxis alone compared with PD stenting plus pharmacological prophylaxis in the prevention of PEP in high risk patients.

Post-ERCP pancreatitis prophylaxis: is it really that complex?

“…Therefore, studies that investigate whether a pure pharmacological approach is equivalent to pharmacological intervention plus PD stenting in preventing PEP are of much interest. This is exactly what Sotoudehmanesh et al from the Tehran University set out to investigate [3].…”

Rectal nonsteroidal anti-inflammatory drugs and pancreatic stents in preventing post-endoscopic retrograde cholangiopancreatography pancreatitis in high-risk patients

“…[ 8 , 9 ] A study comparing pharmacological prophylaxis and pancreatic duct stenting plus pharmacological prophylaxis was excluded. [ 3 ] A study was excluded because PEP was defined in the study by “abdominal pain with elevated serum lipase or amylase no less than 2 times the normal upper limit”, [ 10 ] which was loose compared with the usual definition (abdominal pain with elevated serum lipase more than 3 times the normal upper limit) and probably produced a higher incidence of PEP. Seven studies enrolling patients at low-risk or average-risk of PEP were excluded.…”

“…Notably, several recent studies indicated the combination of rectal NSAIDs and PS did not add benefit compared with rectal NSAIDs or PS alone. [ 3 – 6 ] So we performed this network meta-analysis to compare the efficacies of two prophylactic methods and identify the better one.…”

“…Mechanisms of PEP may contain impaired pancreatic duct drainage, activation of prostaglandin and prostacyclin cascades, and pancreatic tissue ischemia. [ 3 ] Though many strategies including pancreatic stent, allopurinol, diclofenac, indomethacin, octreotide,somatostatin, gabexate, glyceryl trinitrate, ulinastatin, and nafamostat have been reported to prevent PEP or reduce the severity of PEP, the updated European Society of Gastrointestinal Endoscopy (ESGE) guideline only strongly recommends rectal administration of 100 mg diclofenac or indomethacin in all patients, aggressive hydration with lactated Ringer's solution in patients with contraindication to nonsteroidal anti-inflammatory drugs (NSAIDs), and prophylactic pancreatic stenting in selected high risk patients for PEP. Pancreatic stenting (PS) maintains pancreatic drainage, and rectal NSAIDs may inhibit the activation of prostaglandin and prostacyclin cascades.…”

“…Several recent studies indicated the combination of rectal NSAIDs and PS did not add benefit compared with rectal NSAIDs or PS alone. [ 3 – 6 ] So which better prevents PEP in patients at high risk for PEP remains a question considering the cost-effectiveness and rectal NSAIDs’ notable efficacy in average-risk patients. In the absence of direct comparison of randomized controlled trial (RCTs) between 100 mg rectal NSAIDs (diclofenac or indomethacin) and PS, we performed this network meta-analysis.…”