Published online Nov 16, 2020. doi: 10.4253/wjge.v12.i11.469
Peer-review started: April 20, 2020
First decision: June 15, 2020
Revised: June 24, 2020
Accepted: September 18, 2020
Article in press: September 18, 2020
Published online: November 16, 2020
Endoscopic retrograde cholangiopancreatography (ERCP) is one of the most widely performed therapeutic procedures for bile duct access. However, important complications can occur such as: Post-ERCP pancreatitis (PEP), bleeding, puncture and cholangitis. PEP is considered the main complication after the procedure. Large societies such as ASGE, European Society of Gastrointestinal Endoscopy and Japan Gastroenterological Endoscopy Society describe it as a very important complication and methods must be used to prevent and reduce this pathology. Various methods such as using non-steroidal anti-inflammatory drugs (NSAIDs), prostheses, somatostatin and others have been used, but NSAIDs showed a higher rate of effectiveness.
In many studies, NSAIDs have demonstrated good results, but there are also conflicting results. As there is still controversy as to whether the use of NSAIDs would help in reducing PEP, our group carried out the present study including all the randomized controlled trials (RCTs) described in the literature and the results showed that NSAIDs can help in the prevention of PEP.
Our main objective was to determine the effectiveness of NSAIDs vs “Placebo” as a method of choice or first-line therapy to reduce PEP, using the most recent RCTs. All NSAIDs mentioned in the literature, their route of administration and when they should be administered were investigated. In addition, we hope that this research will have important implications within the medical community.
We performed this meta-analysis according to the PRISMA guidelines. Virtual databases were searched up to December 2019 to identify RCTs without date or language restrictions. Following selection of the studies, they were organized according to the PICO criteria and the design followed the JADAD scale. Statistical analysis of the data was performed using RevMan 5.3 software. The main endpoint evaluated in this study was the reduction in the incidence of PEP. Subgroup analyses were also performed and included the severity of pancreatitis, route of administration, time of administration and the types of NSAIDs administered. The results were evaluated with the Higgins test method, using a risk difference with a random effect with a significance of P < 0.05, 95% confidence interval (CI) and interpreted as true heterogeneity.
Twenty-six high quality RCTs examining the use of NSAIDs vs Placebo for the reduction of PEP were included, involving a total of 8143 patients. 4020 patients used NSAIDs before ERCP and 4123 did not use NSAIDs (control group). A total of 298 cases of acute pancreatitis after ERCP were diagnosed in the NSAID group and 484 cases in the placebo group. The risk of PEP was lower (risk difference (RD)) in the NSAID group: -0.04; 95%CI: -0.07 to -0.02; number needed to treat (NNT), 25; P < 0.05. The use of NSAIDs effectively prevented mild pancreatitis compared to the use of placebo (2.5% vs 4.1%; 95%CI: -0.05 to -0.01; NNT, 33; P < 0.05), but data on moderate and severe PEP could not be fully elucidated. Only rectal administration reduced the incidence of PEP with the RD: -0.06 95%CI, -0.08 to -0.04; NNT, 17; P < 0.05.
In conclusion, the use of NSAIDs does reduce the incidence of PEP. In particular, NSAIDs reduce the incidence of mild acute pancreatitis. The most effective drugs were diclofenac and indomethacin. The best route of administration was rectal and the best time for NSAIDs administration was before ERCP.
It is hoped that these findings will help clinicians decide on the best treatment to prevent PEP.