Treating acute pancreatitis: what’s new?

Abstract

The medical treatment of acute pancreatitis continues to focus on supportive care, including fluid therapy, nutrition, and antibiotics, all of which will be critically reviewed. Pharmacologic agents that were previously studied were found to be ineffective likely due to a combination of their targets and flaws in trial design. Potential future pharmacologic agents, particularly those that target intracellular calcium signaling, as well as considerations for trial design will be discussed. As the incidence of acute pancreatitis continues to increase, greater efforts will be needed to prevent hospitalization, readmission and excessive imaging in order to reduce overall healthcare costs. Primary prevention continues to focus on post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis and secondary prevention on cholecystectomy for biliary pancreatitis as well as alcohol and smoking abstinence.

Keywords:

• acute pancreatitis
• clinical trials
• drugs
• medical therapy
• primary prevention
• resource utilization
• secondary prevention

Financial & competing interests disclosure

VK Singh is a consultant to Novo Nordisk, D-Pharm, Interscope, Boston Scientific and AbbVie. VK Singh is also on the advisory board for Enteromedics and Salix and receives travel support from Cook Medical. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Key issues

• Prior trials of pharmacologic agents have not shown a treatment benefit in acute pancreatitis because either their mechanism of action lies too far ‘downstream’ of the initial intracellular events and/or clinical trial design problems.

• Well-designed trials of pharmacologic agents that target calcium signaling within acinar cells represent the clearest prospect for an effective therapy.

• Primary prevention of acute pancreatitis is largely focused on preventing post-ERCP pancreatitis in high-risk patients using rectal NSAIDs and/or pancreatic stents but there are multiple trials currently underway to determine if combinations of pharmacologic agents could potentially replace the use of prophylactic pancreatic stents.

• Secondary prevention focuses on cholecystectomy for acute biliary pancreatitis and counseling on alcohol and smoking abstinence.

• There will be substantial cost savings to the healthcare system if new paradigms of care are considered for the care of the mild acute pancreatitis, if less imaging is pursued and 30-day readmission rates are reduced.

• Studies that have evaluated fluid therapy are hampered by ‘reverse causation’ bias. Future approaches to fluid therapy will need to focus on aggressive hydration of patients at risk of fluid sequestration in combination with agents that address capillary leak.

• Instead of administering enteral nutrition to any patient with predicted severe acute pancreatitis, future efforts will focus on determining which patients are at risk for gut barrier dysfunction and which will require nasoenteral versus oral nutritional support.

• Methods will need to be developed to differentiate the systemic inflammatory response syndrome of acute pancreatitis from that of extrapancreatic infections that occur in up to 25% of patients. This will allow for a more tailored approach to the use and choice of antibiotics.