Meta-Analysis: Nitroglycerin And Wire-guided Cannultion For The Prevention Of Post-ERCP Pancreatitis

To date, acute pancreatitis remains the most common complication of endoscopic retrograde cholangiopancreatography (ERCP). The incidence of post-ERCP pancreatitis (PEP) varies from 1% to 40%, partly as a result of the definition of PEP, but figures of 1.3% to 6.7% are typical in large prospective studies.Generally, ways to prevent of PEP can be divided into two categories: pharmacological and mechanical. Pharmacological agents, including steroids, non-steroidal anti-inflammatory drugs (NSAIDs), somatostatin and its analogue, allopurinol, gabexate and nitroglycerin, have been studied in relation to their potential use for the prevention of PEP. However, most pharmacological prevention has not been proved effective, although rectal non steroidal anti-inflammatory drugs (NSAIDs) were reported to be efficacious in a recent meta-analysis. Furthermore, no pharmaological agents are widely used in routine clinical practice. Panreatic duct (PD) stent placement and wire-guided cannulation (WGC) are the most two common endoscopic techniques used in reducing PEP. The prophylactic use of PD stent in patients at high risk has become standard of care, whereas the use of WGC for PEP has not reached a consensus by endoscopists.The objective of this research is to evaluate the effect of prophylactic nitroglycerin and WGC for the prevention of PEP by performing a meta-analysis.Part One Meta-Analysis:nitroglycerin for the prevention of post-ERCP pancreatitisObjective:To evaluate the effect of prophylactic nitroglycerin in the prevention of PEP by performing a meta-analysis of randomized controlled trials (RCTs).Methods:Electronic databases, including Chinese Bimedical Literature Database (CBM), National Knowledge Infrastructure (CNKI), Wanfang Periodical Database, Weipu Periodical Database, PubMed, EMBASE, the Cochrane library, and the Science Citation Index, were searched to retrieve relevant trials. In addition, meeting abstracts and the reference lists of retrieved articles were reviewed for further relevant studies. The search terms were'glyceryl trinitrate','nitroglycerin','pancreatitis','endoscopic retrograde cholangiopancreatography','ERCP','prevention'and'prophylaxis'.Results:Seven RCTs, enrolling a total of 1836 patients, were included. Meta-analysis of these trials indicated a significant association between the use of nitroglycerin and the reduction of PEP (RR 0.55; 95%CI:0.40-0.76; P= 0.0002); while the incidence of moderate or severe PEP was not significantly reduced by nitroglycerin (RR 0.69; 95%CI:0.42-1.15; P= 0.15). Subsequent sensitive analyses confirmed these results. The pooled need to treat (NNT) with nitroglycerin to prevent one episode of pancreatitis is 21 patients. Subgroup analyses suggested that nitroglycerin administered by the sublingual route may be useful (P=0.001); while administration of nitroglycerin by the transdermal route did not reach statistical significance (P=0.05). The main side effects of nitroglycerin were headache and hypotension.Conclusion:1. Prophylactic use of nitroglycerin can significantly reduce the incidence of PEP; while the incidence of moderate or severe PEP was not significantly reduced by nitroglycerin.2. Administration of nitroglycerin by the sublingual route can significantly reduce the incidence of PEP; while the effects of administration by the transdermal route require further studies to confirm.3. Administration by the sublingual or transdermal route is relatively safe; however, the intravenous way may result severe hemodynamic instability.4. Sample sizes of future RCTs must be sufficient to detect significant differences; and it is better to perform a dose-ranging study to explore the optimum dosage. Part Two Meta-Analysis:Wire-Guided Cannulation for the prevention of post-ERCP pancreatitisObjective:To assess the overall effect of WGC for PEP compared with conventional contrast-assisted cannulation by carrying out a meta-analysis of all available RCTs.Methods:Electronic databases, including Chinese Bimedical Literature Database (CBM), National Knowledge Infrastructure (CNKI), Wanfang Periodical Database, Weipu Periodical Database, PubMed, EMBASE, the Cochrane library, and the Science Citation Index, were searched to retrieve relevant trials. In addition, meeting abstracts and the reference lists of retrieved articles were reviewed for further relevant studies. The search terms were'guidewire','guide wire','endoscopic retrograde cholangiopancreatography','ERCP','pancreatitis'and'cannulation'.Results:Four RCTs, enrolling a total of 1431 patients, were included. The meta-analysis failed to indicate a significant association between the use of WGC and the reduction of PEP (RR 0.34; 95%CI:0.10-1.17; P= 0.09). Subgroup analysis including trials without cross-over design showed a significant benefit with the use of WGC in reducing PEP (RR 0.20; 95%CI:0.09-0.40; P＜0.00001) and trials with precut used also indicated a significant differences between the two groups (RR 0.23; 95%CI:0.11-0.48; P=0.0001). Primary cannulation success was significantly greater with WGC compared with conventional contrast-guided cannulation (RR 1.14; 95%CI:1.07-1.21; P=0.0001); the need for precut was significantly less with WGC compared with conventional contrast-guided cannulation (RR 0.68; 95%CI:0.51-0.91; P=0.009). Complications attributable to guidewires used for ERCP were infrequent.Conclusion:1. This meta-analysis showed only a non-significant reduction in the rate of PEP with the use of WGC. Further well-designed RCT are still required to confirm the effect of WGC.2. The use of the guide wire not only increases the primary cannulation rate but also reduces the need for precut.3. Compared with conventional contrast-guided cannulation, WGC is also safe.