Aprepitant binds to neurokinin-1 receptors and would be expected to antagonize the actions of substance P throughout the body, including the pancreas. Īprepitant is a selective neurokinin-1 receptor antagonist that is currently approved by the United States Food and Drug Administration (FDA) for prevention of chemotherapy-induced and postoperative nausea and vomiting. In a rat model of post-ERCP pancreatitis, intra-ductal administration of a neurokin1 antagonist reduced the severity of inflammation. Substance P binds to the neurokinin-1 receptor in the pancreas to produce these features of neurogenic inflammation. Activation of the capsaicin receptor (TRPV1) on sensory C and Aδ fibers induces the release of substance P, which is associated with pancreatic vasodilation, edema, and cellular infiltration. Thus, there is a continued need for an agent that is both safe and effective at preventing post-ERCP pancreatitis, particularly in high risk patients.Įxperimental models have supported the role of neurogenic inflammation (pathologic activation of sensory neurons) in the pathogenesis of acute pancreatitis. Randomized trials have not consistently demonstrated the efficacy of pharmacologic prophylaxis and many of these agents are not available in the United States. Ī number of pharmacologic agents have been investigated for their potential to reduce the incidence of post-ERCP pancreatitis. Furthermore, pancreatic duct stent placement itself is associated with complications such as migration, obstruction, bleeding, infection, perforation, and cholangitis. Although clinical trials have demonstrated the efficacy of prophylactic pancreatic duct stents at reducing the risk of post- ERCP pancreatitis, the absolute risk reduction is only about 10-15%. Potential mechanisms include sphincter of Oddi spasm and papillary edema from mechanical trauma, hydrostatic injury from saline or contrast, enzymatic injury, bacterial infection, and chemical injury from contrast medium. Established risk factors for acute pancreatitis include those that are patient related (e.g., young age, female gender, and sphincter of Oddi dysfunction) and those that are procedure related (e.g., difficult cannulation, pancreatic duct overinjection, and sphincterotomy). Larger studies potentially using the recently available intravenous formulation are necessary to conclusively clarify the efficacy of aprepitant in this setting.Īprepitant Cholangiopancreatography, Endoscopic Retrograde Pancreatitis Receptors, Neurokinin-1 INTRODUCTIONĪcute pancreatitis can occur as a complication of endoscopic retrograde cholangiopancreatography (ERCP) in up to 40% of high risk patients. Conclusions Aprepitant did not lower incidence of post-ERCP pancreatitis in this preliminary human study. Hospitalization within 7 days post-procedure for abdominal pain that did not meet criteria for acute pancreatitis occurred in 6 and 9 patients in the aprepitant and placebo groups respectively (P=0.772). Incidence of acute pancreatitis was 7 in the aprepitant group and 7 in the placebo group. Results Baseline characteristics were similar between the two groups. Statistics Fisher’s exact test was used to compare incidence of post-ERCP pancreatitis in the two groups. Patients Thirty-four patients received aprepitant and 39 patients received placebo. Intervention Patients at high risk for post-ERCP pancreatitis received either placebo or oral aprepitant administered 4 hours prior to ERCP, 80 mg 24 hours after the first dose, and then 80 mg 24 hours after the second dose. Design Randomized, double-blind, placebo controlled trial at a single academic medical center. Our aim was to assess the efficacy of a neurokinin-1 receptor antagonist (aprepitant) at preventing post-ERCP pancreatitis in high risk patients. Objectives Animal studies have demonstrated a role for substance P binding to neurokinin-1 receptor in the pathogenesis of acute pancreatitis.
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