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

Introduction: Post-endoscopic retrograde cholangiopancreatography pancreatitis (PEP) is a common complication of endoscopic retrograde cholangiopancreatography (ERCP). Multiple drugs and techniques have been studied for the prevention of PEP. Topical epinephrine has recently been studied for the prevention of PEP and theoretically should work similarly as a PD stent. Topical epinephrine sprayed on the ampulla can reduce edema by arteriolar vasoconstriction and therefore improve pancreatic outflow. Evidence regarding the use of topical epinephrine in the prevention of PEP is inconsistent with some studies favoring their use while other studies did not show any benefit. We, therefore, conducted a systematic review and meta-analysis to delineate if topical epinephrine is useful in the prevention of PEP. Methods: A comprehensive literature review was conducted by searching multiple databases until August 2019, to identify all studies that evaluated the use of topical epinephrine alone or in conjunction with other agents for the prevention of PEP. The characteristics of the participants and outcome measurements (incidence of PEP) were analyzed. All analysis was conducted using Revman 5.3. Results: Eight studies, including 6 randomized controlled trials (RCTs) and 2 observational studies with 4123 patients, were included in the meta-analysis. Our overall results included two types of studies. Some studies evaluated both topical epinephrine and rectal indomethacin therapy together and some studies compared topical epinephrine with placebo therapy. Five RCTs are of good quality while one was of fair quality. Both the observational studies were of good quality. Overall, there was no difference in the incidence of PEP in patients who underwent ERCP and were treated with epinephrine spray versus those who were not, OR=0.62 (CI 0.30-1.25) with heterogeneity (I2=72%). In a subgroup analysis, topical epinephrine, when compared to placebo significantly decreases the risk of PEP, OR=0.30 (0.16-0.55). However, in a subgroup analysis, addition of topical epinephrine to rectal indomethacin did not provide any additional advantage in decreasing the incidence of PEP, when compared to rectal indomethacin alone OR=1.15 (0.58-2.28). Conclusion: Topical epinephrine does not provide any additional advantage in combination with rectal indomethacin in the prevention of PEP in patients who underwent ERCP. However, topical epinephrine alone is associated with lower odds of PEP compared to placebo and can be considered if rectal indomethacin is unavailable or there is any contraindication to its use. It may also be considered as a suitable alternative to prophylactic pancreatic stenting. Future studies comparing topical epinephrine versus PD stenting can be considered to evaluate if topical epinephrine provides a similar advantage in decreasing PEP as compared to PD stenting