Meta-analysis On Nonsteroidal Anti-inflammatory Drugs Per-rectum Administration To Prevent Post-endoscopic Retrograde Cholangiopancreatography Pancreatitis

Background:Endoscopic retrograde cholangiopancreatography(ERCP)is a widely used procedure for diagnosis and treatment for bileand pancreas-related diseases including choledocholithiasis,benign and malignant strictures and etc.Post ERCP pancreatitis(PEP)is remains the most common complication of ERCP which occur in 2-10% of patients.Mild course of PEP is associated with prolonged hospitalization,and even serious illness with hemorrhagic pancreatitis,pancreatic necrosis,multi-organ failure,and even death.It has been revealed that ERCP induced systemic inflammatory response is the physiopathological event that triggers PEP.At present,the exact pathological mechanism has not been well elucidated.Previous studies indicated phospholipase A2(PLA2)is an important player in the initiate of inflammatory cascade of acute pancreatitis.As potent inhibitors of PLA2 activity,Per rectum nonsteroidal anti-inflammatory drugs(NSAIDs)administration has been widely used in clinical for PEP prevention.Some early trials and associated meta-analysis show that per rectum NSAIDs administration is safe and effective for PEP prevention.However,most recent published randomized controlled trials(RCTs)revealed single dose rectal indomethacin(100mg)did not prevent PEP compared with the placebo.Also,the comments about the guidelines from different countries are controversial.Objective: The aim of the meta-analysis is to evaluate the efficacy and safety of per rectum NSAIDs for PEP prevention and to provide updated evidence to clarify which type of NSAIDs and administration period is more effective.Methods: The electronic searches were conducted to retrieve Randomized controlled trials(RCTs)from The WanFang Data,VIP,CBM,CNKI,Cochrane Library,PubMed,EMBASE,OVID and Web of Science.all references in all included trials were searched,too.The RCTs on rectal nonsteroidal anti-inflammatory drugs administration for preventing PEP were identified and retrieved.Using the ¨risk of bias¨and ¨modified Jadad scale¨ assessment tool which the Cochrane Collaboration provides,to access the quality of selected articles.All pooled data were analyzed using Review Manager(RevMan)version 5.3 software.Primary endpoint of the study was the efficacy for PEP prevention.Sub-analyses were performed to determine the risk reduction in different NSAIDs types,general and high risk patients,different administration period.The documented data were extracted from among the included studies.Results: Twelve RCTs including a total of 3989 patients(2016 in NSAIDs group and 1973 in control group)were identified and included in the Meta-analysis.The incidence of PEP was lower in the NSAIDs group than that in the placebo group(RR 0.52;95% CI,0.43-0.64;P<0.01)both in high risk patients and unselected patients.The incidence of moderate to severe PEP was also lower in the NSAIDs group.(RR 0.44;95% CI,0.28-0.69;P < 0.01).There is neither a difference in efficacy between rectal indomethacin and diclofenac nor a difference in efficacy between the timing of per rectum NSAIDs administration(pre-or post-ERCP).Conclusions : Prophylactic per rectum NSAIDs administration is effective and safe for PEP prevention both in high risk patients and unselected patients.The efficacy of NSAIDs in the prevention of PEP was not affected by administration period(pre-or post-ERCP)and drug types(diclofenac or indomethacin).