Timing of Administration and Combination Therapy of Non-steroidal Anti-inflammatory Drugs for the Prevention of Post-endoscopic Retrograde Cholangiopancreatography Pancreatitis postprint

Abstract: Background　Endoscopic retrograde cholangiopancreatography（ERCP） is a standard method for the diagnosis and treatment of biliary and pancreatic diseases，but pancreatitis（PEP） after ERCP is a serious complication. Non steroidal anti-inflammatory drugs（NSAIDs） may play a role in the prevention of PEP due to their anti-inflammatory and analgesic effects. To explore the appropriate timing of medication and the effect of combined medication can help reduce the risk of PEP occurrence. Objective　This study aimed to evaluate the administration timing and influencing factors of NSAIDs in PEP prevention，in order to determine the best application in clinical practice. Methods　A total of 866 patients who underwent ERCP in the Department of General Surgery and Oncology of Handan Central Hospital from December 2021 to December 2023 were included as the research objects. According to the random number table method，they were divided into preoperative medication group（431 cases） and postoperative medication group（435 cases）. According to the types of NSAIDs used，they were divided into preoperative medication alone subgroup（210 cases），preoperative combined medication subgroup（221 cases），postoperative medication alone subgroup（247 cases），and postoperative combined medication subgroup（188 cases）. In the preoperative medication alone subgroup，75 mg diclofenac sodium was intramuscularly injected 30 min before ERCP，and in the preoperative medication combination subgroup，100 mg indomethacin suppository was added to the anal plug at the same time；The single drug group was given 75 mg diclofenac sodium intramuscularly immediately after ERCP，and the combined drug group was given 75 mg diclofenac sodium intramuscularly and 100 mg indomethacin suppository anal plug simultaneously after ERCP. All interventions were single dose. The main outcome measures included the incidence and severity of PEP，the incidence of postoperative perforation，bleeding，and cholangitis. The incidence，severity，and adverse reactions of pancreatitis after ERCP were compared between the groups. Multivariate Logistic regression was used to analyze the influencing factors of PEP. Results　There was a statistically significant difference in the incidence of PEP among the four subgroups（P<0.05）. The incidence of PEP in the preoperative medication alone subgroup was lower than that in the postoperative medication alone subgroup and the postoperative combination subgroup（P<0.05），and the incidence of pep in the preoperative combination subgroup was lower than that in the postoperative medication alone subgroup and the postoperative combination subgroup（P<0.05）； There was no significant difference in the severity of PEP and the incidence of adverse reactions among the four groups（P>0.05）. The results of multivariate logistic regression analysis showed that，BMI ≥ 24 kg/m2 （OR=3.751，95%CI=2.293~6.136）， alcohol abuse （OR=2.624，95% CI=1.520-4.529），diabetes mellitus（OR =2.687，95%CI=1.559-4.634），intubation time >10 min（OR=4.229，95%CI=2.531-7.066） and the use of double guide wire technology（OR=3.542，95%CI=2.159-5.809） were the independent risk factors of PEP（P<0.05），B-ultrasound showed that extrahepatic bile duct dilatation was a protective factor for PEP（OR=0.573，95%CI=0.347-0.947）. Conclusion　BMI，alcohol abuse，diabetes，intubation time >10 min and the use of double guide wire technology are independent risk factors for the occurrence of PEP. Before ERCP prophylactic combined use of indomethacin suppository and diclofenac sodium can effectively reduce the risk and severity of PEP，and reduce the incidence of postoperative adverse reactions.