Prevention of post-endscopic retrograde cholangiopancreatography pancreatitis: Do we practice what we preach?

Abstract

Pancreatitis remains the most common and feared adverse event of ERCP, occurring in approximately 8% of average-risk and 15% of high-risk procedures.1Kochar B. Akshintala V.S. Afghani E. et al.Incidence, severity, and mortality of post-ERCP pancreatitis: a systemic review by using randomized controlled trials.Gastrointest Endosc. 2015; 81: 143-149Abstract Full Text Full Text PDF PubMed Scopus (257) Google Scholar Although the majority of cases are mild, nearly 1% are severe, with a mortality approaching 1 in 500 patients.1Kochar B. Akshintala V.S. Afghani E. et al.Incidence, severity, and mortality of post-ERCP pancreatitis: a systemic review by using randomized controlled trials.Gastrointest Endosc. 2015; 81: 143-149Abstract Full Text Full Text PDF PubMed Scopus (257) Google Scholar Post-ERCP pancreatitis (PEP) may occur as the result of mechanical trauma to the pancreatic orifice during attempted cannulation, from thermal injury during sphincterotomy, and/or from excessive injection of hydrostatic fluid/contrast agents into the pancreatic duct that result in obstruction to pancreatic outflow and premature activation of pancreatic enzymes, with subsequent inflammation and injury to the pancreas, which when severe can lead to systemic adverse events and organ failure. Both patient-related and procedure-related factors can contribute to the risk of PEP. Patient-related factors include younger age (<55 years), female sex, history of pancreatitis including PEP, normal serum bilirubin, and suspected sphincter of Oddi dysfunction. Procedure-related factors include difficult cannulation, repeated guidewire cannulation of the pancreatic duct, multiple injections of contrast agent or fluid into the pancreatic duct, balloon dilation of an intact biliary sphincter, pancreatic sphincterotomy (including minor duct sphincterotomy), and snare ampullectomy.2Tringali A. Loperfido S. Costamagna G. Post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis.UpToDate. 2023; (Available at: https://www.uptodate.com/contents/post-endoscopic-retrograde-cholangiopancreatography-ercp-pancreatitis#H9. Accessed April 10, 2023)Google Scholar,3Chandrasekhara V. Khashab M.A. Muthusamy R. et al.Adverse events associated with ERCP.Gastrointest Endosc. 2017; 85: 32-47Abstract Full Text Full Text PDF PubMed Scopus (390) Google Scholar Furthermore, patient-related and procedure-related risk factors appear to be additive, with the risk increasing when >1 risk factor is present.4Freeman M.L. DiSario J.A. Nelson D.B. et al.Risk factors for post-ERCP pancreatitis: a prospective, multicenter study.Gastrointest Endosc. 2001; 54: 425-434Abstract Full Text Full Text PDF PubMed Scopus (999) Google Scholar,5Park C.H. Park S.W. Yang M.J. et al.Pre-and post-procedure risk prediction models for post-endoscopic retrograde cholangiopancreatography pancreatitis.Surg Endosc. 2022; 36: 2052-2061Crossref PubMed Scopus (3) Google Scholar Minimizing the risk of PEP requires careful patient selection and identification of patient and procedural risk factors. MRCP and EUS should be considered for diagnostic imaging, with ERCP reserved for therapeutic indications. Careful and expert ERCP technique, along with consideration of medical interventions and periprocedural maneuvers that have demonstrated effectiveness, can decrease the risk of PEP. Periprocedural administration of rectal indomethacin has been shown to reduce the risk of PEP in high-risk patients.6Elmunzer B.J. Scheiman J.M. Lehman G.A. et al.A randomized trial of rectal indomethacin to prevent post-ERCP pancreatitis.N Engl J Med. 2012; 366: 1414-1422Crossref PubMed Scopus (491) Google Scholar In unselected patients, defined as all patients who presented for ERCP regardless of risk factors, a systematic review and meta-analysis of 18 randomized controlled trials found that the use of rectal nonsteroidal anti-inflammatory drugs (NSAIDs) was associated with a 50% reduction in the risk of PEP.7Buxbaum J.L. Freeman M. Amateau S.K. et al.ASGE Standards of Practice CommitteeAmerican Society for Gastrointestinal Endoscopy guideline on post-ERCP pancreatitis prevention strategies: summary and recommendations.Gastrointest Endosc. 2023; 97: 153-162Abstract Full Text Full Text PDF PubMed Scopus (1) Google Scholar However, a protective effect of rectal NSAIDs has not been clearly demonstrated in studies that included low-risk patients, such as those undergoing routine biliary stent exchange.8Levenick J.M. Gordon S.R. Fadden L.L. et al.Rectal indomethacin does not prevent post-ERCP pancreatitis in consecutive patients.Gastroenterology. 2016; 150: 911-917Abstract Full Text Full Text PDF PubMed Scopus (122) Google Scholar Modification of intraprocedural techniques may also reduce the risk of PEP. In comparison with contrast agent–guided cannulation, wire-guided cannulation may reduce the risk of PEP by as much as 50% and may result in an increase in primary cannulation success.9Tse F. Yuan Y. Moayyedi P. et al.Guide wire-assisted cannulation for the prevention of post-ERCP pancreatitis: a systemic review and meta-analysis.Endoscopy. 2013; 45: 605-618Crossref PubMed Scopus (88) Google Scholar,10Tse F. Liu J. Yuan Y. et al.Guidewire-assisted cannulation of the common bile duct for the prevention of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis.Cochrane Database System Rev. 2022; 3: CD009662PubMed Google Scholar Furthermore, several randomized controlled trials and meta-analyses have shown that placement of a prophylactic pancreatic duct stent can reduce the incidence and the severity of PEP, especially in high-risk patients (difficult cannulation, repeated pancreatic duct access, precut sphincterotomy, ampullectomy, or history of PEP) by as much as 65%.7Buxbaum J.L. Freeman M. Amateau S.K. et al.ASGE Standards of Practice CommitteeAmerican Society for Gastrointestinal Endoscopy guideline on post-ERCP pancreatitis prevention strategies: summary and recommendations.Gastrointest Endosc. 2023; 97: 153-162Abstract Full Text Full Text PDF PubMed Scopus (1) Google Scholar,11Choudhary A. Bechtold M.L. Arif M. et al.Pancreatic stents for prophylaxis against post-ERCP pancreatitis: a meta-analysis and systemic review.Gastrointest Endosc. 2011; 73: 275-282Abstract Full Text Full Text PDF PubMed Scopus (208) Google Scholar However, pancreatic duct stenting can be technically challenging, and unsuccessful pancreatic duct stenting when attempted confers an independent increased risk of PEP.12Choksi N.S. Fogel E.L. Cote G.A. et al.The risk of post-ERCP pancreatitis and the protective effect of rectal indomethacin in cases of attempted but unsuccessful prophylactic pancreatic stent placement.Gastrointest Endosc. 2015; 81: 150-155Abstract Full Text Full Text PDF PubMed Scopus (51) Google Scholar Additionally, there is evidence to support aggressive periprocedural and postprocedural intravenous hydration when medically tolerable, especially when lactated Ringer’s solution is used, in reducing the risk of PEP.7Buxbaum J.L. Freeman M. Amateau S.K. et al.ASGE Standards of Practice CommitteeAmerican Society for Gastrointestinal Endoscopy guideline on post-ERCP pancreatitis prevention strategies: summary and recommendations.Gastrointest Endosc. 2023; 97: 153-162Abstract Full Text Full Text PDF PubMed Scopus (1) Google Scholar,13Radadiya D. Devani K. Arora A. et al.Peri-procedural aggressive hydration for post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis prophylaxis: meta-analysis of randomized controlled trials.Pancreatology. 2019; 19: 819-827Crossref PubMed Scopus (27) Google Scholar Despite the beneficial effects of those measures in reducing PEP and societal guidelines endorsing their use,3Chandrasekhara V. Khashab M.A. Muthusamy R. et al.Adverse events associated with ERCP.Gastrointest Endosc. 2017; 85: 32-47Abstract Full Text Full Text PDF PubMed Scopus (390) Google Scholar,7Buxbaum J.L. Freeman M. Amateau S.K. et al.ASGE Standards of Practice CommitteeAmerican Society for Gastrointestinal Endoscopy guideline on post-ERCP pancreatitis prevention strategies: summary and recommendations.Gastrointest Endosc. 2023; 97: 153-162Abstract Full Text Full Text PDF PubMed Scopus (1) Google Scholar,14Dumonceau J.M. Andriulli A. Elmunzer B.J. et al.Prophylaxis of post-ERCP pancreatitis: European Society of Gastrointestinal Endoscopy (ESGE) guideline - updated June 2014.Endoscopy. 2014; 46: 799-815Crossref PubMed Scopus (403) Google Scholar the overall rate of PEP has not been decreasing, and hospitalizations and mortality from PEP appear to be on the rise.15Smith Z.L. Elmunzer B.J. Cooper G.S. et al.Real-world practice patterns in the era of rectal indomethacin for prophylaxis against post-ERCP pancreatitis in a high-risk cohort.Am J Gastroenterol. 2020; 115: 934-940Crossref PubMed Scopus (13) Google Scholar,16Mutneja H.R. Vohra I. Go A. et al.Temporal trends and mortality of post-ERCP pancreatitis in the United States: a nationwide analysis.Endoscopy. 2021; 53: 357-366Crossref PubMed Scopus (20) Google Scholar The extent to which prophylactic interventions, especially rectal indomethacin and/or pancreatic stents, are used in the United States is unclear, and understanding practice patterns and adherence to guidelines may be informative regarding this dilemma. In this issue of Gastrointestinal Endoscopy, Ashat et al17Ashat M. Kandula S. Cote G.A. et al.Utilization pattern of prophylactic measures for prevention of post-ERCP pancreatitis: a National Survey Study.Gastrointest Endosc. 2023; 97: 1059-1066.e3Abstract Full Text Full Text PDF Scopus (1) Google Scholar attempt to answer this question. The aim of the study was to describe the utilization pattern of various measures to decrease the risk of PEP among interventional endoscopists who perform ERCP in the United States and to identify factors that may affect the use of these prophylactic measures by way of a 27-question electronic survey distributed to American Society for Gastrointestinal Endoscopy members with an active ERCP practice. Of 391 respondents, 47% had completed an advanced endoscopy fellowship, and 37% practiced in a teaching hospital. Whereas 47% of the respondents performed >100 ERCPs per year, the majority (61%) did very few pancreatic ERCPs (≤5% procedure volume). Encouragingly, most (89%) of the respondents reported that they used rectal indomethacin, whereas fewer (54%) used prophylactic pancreatic stents and typically only in high-risk patients or to facilitate biliary access. Of those who did not use pancreatic stents, the most common reason was the use of rectal indomethacin instead, whereas fewer performed ERCP only in low-risk situations or did not feel comfortable or have the expertise for placing pancreatic stents. Endoscopists with ERCP fellowship training, those who worked in teaching hospitals, younger physicians, those with higher procedural volumes, and those who did more pancreatic cases were more likely to use pancreatic stents. The survey was not designed to detect or identify the use of combined rectal indomethacin and pancreatic stents to prevent PEP. Additionally, almost 90% reported the use of periprocedural intravenous fluid resuscitation, with most (81%) using lactated Ringer’s solution. The following conclusions are evident from this survey: First, rectal indomethacin use appears to be more frequent than pancreatic stent placement and is becoming the preferred method for PEP prophylaxis. Second, placement of prophylactic pancreatic stents, not surprisingly, is more likely to be performed by physicians who have more expertise, including those with previous advanced endoscopy fellowship training and higher procedural volumes, and who perform ERCP in more complex patients in teaching hospitals. Although it is encouraging that there appears to be almost universal acceptance of rectal indomethacin for PEP prophylaxis among survey respondents, as the authors state, a self-reported survey is inherently subject to recall and selection bias; as such, the actual use of rectal indomethacin in practice may be much less. A smaller survey of advanced endoscopists in the United States in 2019 showed that fewer than half of respondents were using rectal NSAIDs in average-risk patients.18Avila P. Holmes I. Kouanda A. et al.Practice patterns of post-ERCP pancreatitis prophylaxis techniques in the United States: a survey of advanced endoscopists.Gastrointest Endosc. 2020; 91: 568-573Abstract Full Text Full Text PDF PubMed Scopus (17) Google Scholar Additionally, a retrospective analysis of a large database obtained from the electronic medical records of high-risk patients undergoing ERCP found a linear increase in the use of indomethacin beginning in 2012 but still remained below 50% by 2018. Furthermore, as indomethacin use has increased, the use of prophylactic pancreatic stents has declined considerably.15Smith Z.L. Elmunzer B.J. Cooper G.S. et al.Real-world practice patterns in the era of rectal indomethacin for prophylaxis against post-ERCP pancreatitis in a high-risk cohort.Am J Gastroenterol. 2020; 115: 934-940Crossref PubMed Scopus (13) Google Scholar If we want to minimize the risk of ERCP including PEP, we need to practice high-quality ERCP in appropriate patients while adhering to evidence-based guidelines that include rectal NSAIDs in all but low-risk patients, and to consider placing prophylactic pancreatic stents when feasible in high-risk patients. The role of combination therapy remains uncertain, but we anxiously await the results of an ongoing trial that aims to show whether pancreatic stent plus indomethacin performs better than indomethacin alone in high-risk patients.19Elmunzer B.J. Serrano J. Chak A. et al.Rectal indomethacin alone versus indomethacin and prophylactic pancreatic stent placement for preventing pancreatitis after ERCP: study protocol for a randomized control trial.Trials. 2016; 17: 120Crossref PubMed Google Scholar Educational efforts and quality assurance measures to improve adherence to these guidelines are welcomed. When it comes to PEP prevention, we need to practice what we preach. We owe it to our patients. Dr Gordon is a consultant for Boston Scientific.