Buprenorphine affects the initiation and severity of interleukin-induced acute pancreatitis in mice.

Acute pancreatitis (AP) is a common disease with no targeted therapy and has varied outcomes ranging from spontaneous resolution to being lethal. Although typically painful, AP can also be painless. Various agents, including opioids, are used for pain control in AP; the risks and benefits of which are often debated. As experimental AP in mice is used to study the efficacy of potential therapies, we studied the effect of a commonly used opioid, buprenorphine, on the initiation and progression of AP. For this, we administered extended-release buprenorphine subcutaneously before inducing the previously established severe AP model that uses interleukins 12 and 18 (IL12,18) in genetically obese (ob/ob) mice and compared this to mice with AP but without the drug. Mice were monitored over 3 days, and parameters of AP induction and progression were compared. Buprenorphine significantly reduced serum amylase, lipase, pancreatic necrosis, and AP-associated fat necrosis, which is ubiquitous in obese mice and humans. Buprenorphine delayed the AP-associated reduction of carotid artery pulse distention and the development of hypothermia, hastened renal injury, and muted the early increase in respiratory rate versus IL12,18 alone. The site of buprenorphine injection appeared erythematous, inflamed, and microscopically showed thinning, loss of epidermal layers that had increased apoptosis. In summary, subcutaneous extended-release buprenorphine interfered with the induction of AP by reducing serum amylase, lipase, pancreatic and fat necrosis, the worsening of AP by delaying hypotension, hypothermia, while hastening renal injury, respiratory depression, and causing cutaneous injury at the site of injection.NEW & NOTEWORTHY Extended-release buprenorphine interferes with the initiation and progression of acute pancreatitis at multiple levels.

NSAIDs do not reduce severity among post-ERCP pancreatitis patients.

OBJECTIVE: Non-steroidal anti-inflammatory drugs (NSAIDs) are the most studied chemoprophylaxis for post-endoscopic retrograde cholangiopancreatography pancreatitis (PEP). While previous systematic reviews have shown NSAIDs reduce PEP, their impact on moderate to severe PEP (MSPEP) is unclear. We conducted a systematic review and meta-analysis to understand the impact of NSAIDs on MSPEP among patients who developed PEP. We later surveyed physicians' understanding of that impact. DESIGN: A systematic search for randomized trials using NSAIDs for PEP prevention was conducted. Pooled-prevalence and Odds-ratio of PEP, MSPEP were compared between treated vs. control groups. Analysis was performed using R software. Random-effects model was used for all variables. Physicians were surveyed via email before and after reviewing our results. RESULTS: 7688 patients in 25 trials were included. PEP was significantly reduced to 0.598 (95%CI, 0.47-0.76) in the NSAIDs group. Overall burden of MSPEP was reduced among all patients undergoing ERCP: OR 0.59 (95%CI, 0.42-0.83). However, NSAIDs didn't affect the proportion of MSPEP among those who developed PEP (p = 0.658). Rectal Indomethacin and diclofenac reduced PEP but not MSPEP. Efficacy didn't vary by risk, timing of administration, or bias-risk. Survey revealed a change in the impression of the effect of NSAIDs on MSPEP after reviewing our results. CONCLUSIONS: Rectal diclofenac or indomethacin before or after ERCP reduce the overall burden of MSPEP by reducing the pool of PEP from which it can arise. However, the proportion of MSPEP among patients who developed PEP is unaffected. Therefore, NSAIDs prevent initiation of PEP, but do not affect severity among those that develop PEP. Alternative modalities are needed to reduce MSPEP among patients who develop PEP.