American Society for Gastrointestinal Endoscopy guideline on post-ERCP pancreatitis prevention strategies: summary and recommendations

This guideline document was prepared by the Standards of Practice Committee of the American Society for Gastrointestinal Endoscopy using the best available scientific evidence and considering a multitude of variables including, but not limited to, adverse events, patients' values, and cost implications. The purpose of these guidelines is to provide the best practice recommendations that may help standardize patient care, improve patient outcomes, and reduce variability in practice. We recognize that clinical decision-making is complex. Guidelines, therefore, are not a substitute for a clinician's judgment. Such judgements may, at times, seem contradictory to our guidance because of many factors that are impossible to fully consider by guideline developers. Any clinical decisions should be based on the clinician's experience, local expertise, resource availability, and patient values and preferences. This document is not a rule and should not be construed as establishing a legal standard of care or as encouraging, advocating for, mandating, or discouraging any particular treatment. Our guidelines should not be used in support of medical complaints, legal proceedings, and/or litigation, as they were not designed for this purpose. This clinical practice guideline from the American Society for Gastrointestinal Endoscopy provides an evidence-based approach for strategies to prevent post-ERCP pancreatitis. This document was developed using the Grading of Recommendations Assessment, Development and Evaluation framework. The guideline addresses the role of rectal nonsteroidal anti-inflammatory drugs (NSAIDs), contrast-guided versus wire-assisted cannulation, prophylactic pancreatic stents, and aggressive versus moderate hydration in unselected patients, those without risk factors, to decrease the risk of post-ERCP pancreatitis. Before starting an ERCP, we recommend rectal NSAIDs in all (unselected and high-risk) patients. During an ERCP, we suggest wire-assisted cannulation rather than a contrast-guided approach and placement of prophylactic pancreatic stents in high-risk patients. In the periprocedure period and after ERCP, we suggest aggressive hydration in unselected patients. ERCP enables minimally invasive treatment of a wide range of pancreaticobiliary conditions with substantially lower morbidity than traditional operative approaches.1Lai E.C. Mok F.P. Tan E.S. et al.Endoscopic biliary drainage for severe acute cholangitis.N Engl J Med. 1992; 326: 1582-1586Crossref PubMed Scopus (505) Google Scholar, 2Speer A.G. Cotton P.B. Russell R.C. et al.Randomised trial of endoscopic versus percutaneous stent insertion in malignant obstructive jaundice.Lancet. 1987; 2: 57-62Abstract PubMed Scopus (639) Google Scholar, 3Smith A.C. Dowsett J.F. Russell R.C. et al.Randomised trial of endoscopic stenting versus surgical bypass in malignant low bile duct obstruction.Lancet. 1994; 344: 1655-1660Abstract PubMed Scopus (825) Google Scholar The most feared adverse event (AE) of ERCP is post-ERCP pancreatitis (PEP), which occurs in approximately 8% of average-risk and 15% of high-risk procedures and is the most frequent serious AE of GI endoscopy.4Kochar B. Akshintala V.S. Afghani E. et al.Incidence, severity, and mortality of post-ERCP pancreatitis: a systematic review by using randomized, controlled trials.Gastrointest Endosc. 2015; 81: 143-149Abstract Full Text Full Text PDF PubMed Scopus (296) Google Scholar Although typically mild, PEP is associated with mortality in 1 in 500 patients and an annual nationwide cost of several hundred million dollars.4Kochar B. Akshintala V.S. Afghani E. et al.Incidence, severity, and mortality of post-ERCP pancreatitis: a systematic review by using randomized, controlled trials.Gastrointest Endosc. 2015; 81: 143-149Abstract Full Text Full Text PDF PubMed Scopus (296) Google Scholar Investigators have aimed to attenuate this risk. PEP results from mechanical, thermal, and/or chemical trauma to the pancreatic duct (PD) and papilla. Obstruction because of edema results in intrapancreatic activation of digestive enzymes and injury to the gland.5Saluja A. Saluja M. Villa A. et al.Pancreatic duct obstruction in rabbits causes digestive zymogen and lysosomal enzyme colocalization.J Clin Invest. 1989; 84: 1260-1266Crossref PubMed Scopus (141) Google Scholar,6Ohshio G. Saluja A. Steer M.L. Effects of short-term pancreatic duct obstruction in rats.Gastroenterology. 1991; 100: 196-202Crossref PubMed Google Scholar The consequent inflammatory cascade mediated by cytokines and chemokines including prostaglandins results in intense inflammation.7Makela A. Kuusi T. Schroder T. Inhibition of serum phospholipase-A2 in acute pancreatitis by pharmacological agents in vitro.Scand J Clin Lab Invest. 1997; 57: 401-407Crossref PubMed Scopus (117) Google Scholar Local injury is exacerbated by regional pancreatic hypoperfusion8Kusterer K. Enghofer M. Zendler S. et al.Microcirculatory changes in sodium taurocholate-induced pancreatitis in rats.Am J Physiol. 1991; 260: G346-G351PubMed Google Scholar,9Juvonen P.O. Tenhunen J.J. Heino A.A. et al.Splanchnic tissue perfusion in acute experimental pancreatitis.Scand J Gastroenterol. 1999; 34: 308-314Crossref PubMed Scopus (42) Google Scholar and intravascular hypovolemia because of capillary leak and resulting in systemic AEs including organ failure associated with severe PEP.10Garg P.K. Singh V.P. Organ failure due to systemic injury in acute pancreatitis.Gastroenterology. 2019; 156: 2008-2023Abstract Full Text Full Text PDF PubMed Scopus (230) Google Scholar,11Whitcomb D.C. Muddana V. Langmead C.J. et al.Angiopoietin-2, a regulator of vascular permeability in inflammation, is associated with persistent organ failure in patients with acute pancreatitis from the United States and Germany.Am J Gastroenterol. 2010; 105: 2287-2292Crossref PubMed Scopus (55) Google Scholar Historically, trials of prophylactic agents including corticosteroids, octreotide, and protease inhibitors showed early promise but ultimately disappointing results in larger controlled trials.12Andriulli A. Leandro G. Federici T. et al.Prophylactic administration of somatostatin or gabexate does not prevent pancreatitis after ERCP: an updated meta-analysis.Gastrointest Endosc. 2007; 65: 624-632Abstract Full Text Full Text PDF PubMed Scopus (121) Google Scholar,13Sherman S. Blaut U. Watkins J.L. et al.Does prophylactic administration of corticosteroid reduce the risk and severity of post-ERCP pancreatitis? A randomized, prospective, multicenter study.Gastrointest Endosc. 2003; 58: 23-29Abstract Full Text Full Text PDF PubMed Scopus (69) Google Scholar More recently, several strategies have been shown to offer more consistent benefits. These interventions aimed to alleviate mechanical obstruction resulting from papillary trauma (ie, pancreatic stents), inhibit the pancreatitis-related inflammatory cascade (ie, nonsteroidal anti-inflammatory drugs [NSAIDs]), and prevent regional and systemic hypoperfusion that may contribute to injury (ie, aggressive hydration). Despite the proven benefits of these interventions, their use in routine practice in North America remains suboptimal for a variety of reasons.14Avila 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 (20) Google Scholar, 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 (17) 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 (32) Google Scholar Although we have provided previous recommendations on strategies to minimize overall risk of ERCP, this is the first American Society for Gastrointestinal Endoscopy (ASGE) guideline dedicated to providing evidence-based guidance to mitigate the risk of PEP.17Chandrasekhara V. Khashab M.A. Muthusamy V.R. et al.ASGE Standards of Practice CommitteeAdverse events associated with ERCP.Gastrointest Endosc. 2017; 85: 32-47Abstract Full Text Full Text PDF PubMed Scopus (448) Google Scholar This document was prepared by the Standards of Practice Committee of the ASGE and was conceptualized and conducted according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE). The GRADE panel developed recommendations based on certainty in the evidence and the overall balance of benefit and harm, patient values and preferences, cost-effectiveness, and resource utilization.18Guyatt G.H. Oxman A.D. Vist G.E. et al.GRADE: an emerging consensus on rating quality of evidence and strength of recommendations.BMJ. 2008; 336: 924-926Crossref PubMed Google Scholar,19Wani S. Sultan S. Qumseya B. et al.The ASGE'S vision for developing clinical practice guidelines: the path forward.Gastrointest Endosc. 2018; 87: 932-933Abstract Full Text Full Text PDF PubMed Scopus (15) Google Scholar Consensus among the panel members was used to determine the wording of the recommendation and, in particular, the direction and strength. Using the GRADE approach, we categorized the recommendations as strong or conditional; "recommend" was used for strong recommendations and "suggest" for conditional recommendations. Further details of the methodology used for this guideline are presented separately, including systematic reviews, evidence profile, and results from all meta-analyses.20Buxbaum 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: methodology and review of evidence.Gastrointest Endosc. 2023; 97: 163-183Abstract Full Text Full Text PDF Scopus (4) Google Scholar These guidelines addressed the following clinical questions using the GRADE format:1.In unselected patients undergoing ERCP, should rectal NSAIDs be given to prevent PEP?2.In high-risk patients undergoing ERCP, should rectal NSAIDs be given to prevent PEP?3.In unselected patients undergoing ERCP, is wire-guided cannulation preferred to contrast-guided cannulation to minimize PEP?4.In high-risk patients undergoing ERCP, should pancreatic stents be placed to prevent PEP?5.In unselected patients undergoing ERCP, should aggressive periprocedural and postprocedural intravenous hydration be given to prevent PEP? Relevant clinical outcomes included PEP, moderately severe/severe PEP, and AEs. Details of our literature search, data analyses, pooled-effect estimates, evidence profiles, forest plots, and panel deliberation for each outcome can be found in the methodology and technical review document. A summary of our final recommendations is listed in Table 1.Table 1Summary of recommendationsTimingGRADE recommendationGeneral conceptsPreprocedureAmong unselected patients undergoing ERCP, the ASGE recommends preprocedural rectal NSAIDs to prevent PEP (Strong recommendation/Moderate quality of evidence).•Avoid in patients with recent peptic ulcer disease or renal insufficiency•Can be administered >30 min before or during the procedure•Use indomethacin 100 mg in adultsFor high-risk patients undergoing ERCP, the ASGE recommends preprocedural rectal NSAIDs should be given to prevent PEP (Strong recommendation/Moderate quality of evidence)•Avoid in patients with recent peptic ulcer disease or renal insufficiency•Can be administered >30 min before or during the procedureIntraprocedureIn unselected patients undergoing ERCP, the ASGE suggests wire-guided cannulation over contrast-guided cannulation to minimize the risk of PEP (Conditional recommendation/Moderate quality of evidence).•Cannulate then advance wire•Endoscopist, or experienced operator, to perform wire manipulation•Avoid forceful or repeated wire advancement into the pancreatic ductIn high-risk patients undergoing ERCP, the ASGE recommends that pancreatic stents be used to prevent PEP in high-risk patients in which the pancreatic duct has been repeatedly or deeply accessed (Strong recommendation/Moderate quality of evidence) and suggests it for high-risk patients as long as pancreatic duct access can be easily achievable (Conditional recommendation/Moderate quality of evidence).•Use 3F-5F stent (preferably 5F) without internal flange 3-7 cm in length•If wire cannot pass beyond the head, a short stent (2-3 cm) may be used•Get an abdominal x-ray to assess spontaneous stent migration•Remove in 2-4 weeks if neededPostprocedureIn unselected patients undergoing ERCP, the ASGE suggests aggressive periprocedural and postprocedural intravenous hydration to prevent PEP pancreatitis (Conditional recommendation/Moderate quality of evidence).•Can be initiated preprocedure or intraprocedure•Avoid in patients with history of congestive heart failure, renal insufficiency, or advanced liver disease•Use lactate Ringer's solution•Periprocedural bolus of 20 mL/kg followed by 3 mL/kg/h for 8 h•May be more feasible for inpatientsGRADE, Grading of Recommendations Assessment, Development and Evaluation; ASGE, American Society for Gastrointestinal Endoscopy; NSAID, nonsteroidal anti-inflammatory drug; PEP, post-ERCP pancreatitis. Open table in a new tab GRADE, Grading of Recommendations Assessment, Development and Evaluation; ASGE, American Society for Gastrointestinal Endoscopy; NSAID, nonsteroidal anti-inflammatory drug; PEP, post-ERCP pancreatitis. Recommendation 1: Among unselected patients undergoing ERCP, the ASGE recommends periprocedural rectal NSAIDs should be given to prevent PEP (Strong recommendation/Moderate quality of evidence). Recommendation 1: Among unselected patients undergoing ERCP, the ASGE recommends periprocedural rectal NSAIDs should be given to prevent PEP (Strong recommendation/Moderate quality of evidence). We performed a systematic review and meta-analysis and identified 18 randomized controlled trials (RCTs) of rectal NSAIDs to prevent PEP in a total of 4817 unselected (ie, with and without risk factors) patients. Outcomes of interest included development of PEP, moderately severe or severe PEP, and the AEs of renal failure and GI hemorrhage (ie, postsphincterotomy bleeding). Unselected patients were defined as all patients who presented for ERCP without selection based on risk factors. Among all patients, rectal NSAIDs were associated with a significant reduction in the odds of PEP (odds ratio [OR], .49; 95% confidence interval [CI], .37-.65; I2 = 38.6%). This means that using rectal NSAIDs is associated with a 50% reduction in the risk of PEP. There was a trend toward a reduction of moderately severe and/or severe pancreatitis (OR, .47; 95% CI, .21-1.06; I2 = 38.6%), but this did not reach statistical significance. There was no difference in postsphincterotomy bleeding (OR, 1.68; 95% CI, .50-5.68; I2 = 39%), whereas renal failure did not develop in any patient. Most excluded patients had active peptic ulcer disease, ongoing NSAID use, and renal insufficiency (ie, creatinine level >1.4 mg/dL). A recent study reported that rectal NSAIDs are cost-effective in unselected patients with an incremental cost-effectiveness ratio/quality-adjusted life year (ICER/QALY) of $33,812.21Thiruvengadam N.R. Saumoy M. Schneider Y. et al.A cost-effectiveness analysis for post-endoscopic retrograde cholangiopancreatography pancreatitis prophylaxis in the United States.Clin Gastroenterol Hepatol. 2022; 20: 216-226Abstract Full Text Full Text PDF PubMed Scopus (6) Google Scholar The panel also noted that the overall cost of rectal NSAIDs is small, and the medication is readily available in most settings. The panel raised concerns about recent extreme increases in the price of rectal NSAIDs, especially in the United States.22Elmunzer B.J. Hernandez I. Gellad W.F. The skyrocketing cost of rectal indomethacin.JAMA Intern Med. 2020; 180: 631-632Crossref PubMed Scopus (12) Google Scholar Over-the-counter formulations of NSAIDs are inexpensive. However, when given in hospital settings, prices seem to be multiplied. Furthermore, the wholesale acquisition cost of rectal indomethacin increased from $2 to $340 between 2005 and 2019.22Elmunzer B.J. Hernandez I. Gellad W.F. The skyrocketing cost of rectal indomethacin.JAMA Intern Med. 2020; 180: 631-632Crossref PubMed Scopus (12) Google Scholar Nevertheless, modeling suggests that rectal indomethacin will remain cost-effective up to a price of $1134 per suppository.21Thiruvengadam N.R. Saumoy M. Schneider Y. et al.A cost-effectiveness analysis for post-endoscopic retrograde cholangiopancreatography pancreatitis prophylaxis in the United States.Clin Gastroenterol Hepatol. 2022; 20: 216-226Abstract Full Text Full Text PDF PubMed Scopus (6) Google Scholar Other NSAIDs, which are not available as rectal preparations on the market, may be formulated from oral medications by compounding pharmacies at substantially lower cost. A limitation of the data is that the inclusion criteria and study populations were heterogeneous. Unselected patients included mixed high-, medium-, and low-risk patients, and results were not stratified. Although the studies did not select for PEP risk factors, most excluded patients with very-low-risk indications such as biliary stent exchange. Of note, these very-low-risk patients were included in the trial by Levenick et al,23Levenick J.M. Gordon S.R. Fadden L.L. et al.Rectal indomethacin does not prevent post-ERCP pancreatitis in consecutive patients.Gastroenterology. 2016; 150 (quiz e19): 911-917Abstract Full Text Full Text PDF PubMed Scopus (130) Google Scholar which did not demonstrate a protective effect for rectal NSAIDs. Hence, the available literature does not inform the clinical and cost-to-benefit impact of rectal NSAIDS for low-risk patients. Timing of rectal NSAID administration ranged from 90 minutes before the procedure to the time of arrival in the recovery room.24Li L. Liu M. Zhang T. et al.Indomethacin down-regulating HMGB1 and TNF-alpha to prevent pancreatitis after endoscopic retrograde cholangiopancreatography.Scand J Gastroenterol. 2019; 54: 793-799Crossref PubMed Scopus (8) Google Scholar In all but 3 studies they were given before ERCP. We compared efficacy among patients who received the dose ≥30 minutes before with those who received the medication closer to or during the procedure and did not identify a difference. Although ketoprofen and naproxen suppositories have been studied for PEP prevention, the great preponderance of data focuses on rectal indomethacin and diclofenac. Both rectal indomethacin and diclofenac were found to be effective in subgroup analyses. The standard dose for rectal indomethacin and diclofenac is 100 mg. In pediatric patients, the NSAID dose is to be determined by the pediatrician. Clinical trials excluded patients with peptic ulcer disease and renal insufficiency; therefore, based on the currently available data, such patients may not be good candidates for NSAIDs. In addition, patients with known aspirin or other nonsteroidal allergies should not receive rectal NSAIDs. In summary, given the significant reduction in PEP, cost-effectiveness, and minimal AEs, the panel made a strong recommendation for use of rectal NSAIDs in unselected patients undergoing ERCP. The overall quality of the evidence was moderate. Recommendation 2: For high-risk patients undergoing ERCP, the ASGE recommends periprocedural rectal NSAIDs should be given to prevent PEP (Strong recommendation/moderate quality of evidence). Recommendation 2: For high-risk patients undergoing ERCP, the ASGE recommends periprocedural rectal NSAIDs should be given to prevent PEP (Strong recommendation/moderate quality of evidence). To address this question, we performed a systematic review and meta-analysis of randomized trials and identified 10 eligible studies with 1008 patients in populations defined by the authors of the RCTs as high risk for PEP. The high-risk status was based on baseline features or technical challenges during ERCP. Outcomes of interest included overall risk of PEP, risk of moderately severe or severe PEP (consensus or revised Atlanta classification), renal failure, and GI bleeding (ie, postsphincterotomy bleeding). For the outcome of overall risk of PEP, the OR was .49 (95% CI, .30-.83; I2 = 56.6%) with prophylactic NSAIDs compared with placebo. This means that using rectal NSAIDs is associated with a 50% reduction in the risk of PEP in high-risk patients. There was a trend toward lower risk of moderately severe or severe pancreatitis; however, this did not reach statistical significance (OR, .53; 95% CI, .27-1.05; I2 = 11.8%). There was no difference in renal failure (OR, .63; 95% CI, .12-3.29; I2 = 0) or bleeding (OR, .82; 95% CI, .40-1.65; I2 = 0) with NSAID use. A recent cost-effectiveness analysis revealed that rectal NSAIDS are cost-effective in high-risk patients.21Thiruvengadam N.R. Saumoy M. Schneider Y. et al.A cost-effectiveness analysis for post-endoscopic retrograde cholangiopancreatography pancreatitis prophylaxis in the United States.Clin Gastroenterol Hepatol. 2022; 20: 216-226Abstract Full Text Full Text PDF PubMed Scopus (6) Google Scholar In several studies a significant proportion of patients also received a pancreatic stent to prevent PEP.25Elmunzer 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 (528) Google Scholar,26Mok S.R.S. Ho H.C. Shah P. et al.Lactated Ringer's solution in combination with rectal indomethacin for prevention of post-ERCP pancreatitis and readmission: a prospective randomized, double-blinded, placebo-controlled trial.Gastrointest Endosc. 2017; 85: 1005-1013Abstract Full Text Full Text PDF PubMed Scopus (62) Google Scholar Thus far, trials to compare whether NSAIDs alone versus NSAIDs combined with pancreatic stents are optimal to prevent PEP in high-risk patients have been underpowered, although a large ongoing multicenter RCT aims to address this question.27Sotoudehmanesh R. Ali-Asgari A. Khatibian M. et al.Pharmacological prophylaxis versus pancreatic duct stenting plus pharmacological prophylaxis for prevention of post-ERCP pancreatitis in high risk patients: a randomized trial.Endoscopy. 2019; 51: 915-921Crossref PubMed Scopus (29) Google Scholar, 28Elmunzer 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 controlled trial.Trials. 2016; 17: 120Crossref PubMed Google Scholar, 29Koshitani T. Konaka Y. Nakano K. et al.Rectal nonsteroidal anti-inflammatory drugs are equivalent to pancreatic duct stents in preventing pancreatitis after endoscopic retrograde cholangiopancreatography [abstract].Gastrointest Endosc. 2017; 85: AB213-A214Abstract Full Text Full Text PDF Google Scholar Additionally, the definition of high-risk conditions continues to evolve as clinical practice patterns change. Sphincter of Oddi dysfunction was the predominant indication in several larger trials of NSAIDs that demonstrated benefit.22Elmunzer B.J. Hernandez I. Gellad W.F. The skyrocketing cost of rectal indomethacin.JAMA Intern Med. 2020; 180: 631-632Crossref PubMed Scopus (12) Google Scholar,30Murray B. Carter R. Imrie C. et al.Diclofenac reduces the incidence of acute pancreatitis after endoscopic retrograde cholangiopancreatography.Gastroenterology. 2003; 124: 1786-1791Abstract Full Text Full Text PDF PubMed Scopus (236) Google Scholar Female gender, age <40 years, and normal bilirubin are predictors of PEP, but with increasing recognition that sphincter of Oddi dysfunction is a suboptimal indication for ERCP, their importance when associated with other pathologies is less clear.31Freeman M.L. Nelson D.B. Sherman S. et al.Complications of endoscopic biliary sphincterotomy.N Engl J Med. 1996; 335: 909-918Crossref PubMed Scopus (2254) Google Scholar, 32Cotton P.B. Durkalski V. Romagnuolo J. et al.Effect of endoscopic sphincterotomy for suspected sphincter of Oddi dysfunction on pain-related disability following cholecystectomy: the EPISOD randomized clinical trial.JAMA. 2014; 311: 2101-2109Crossref PubMed Scopus (168) Google Scholar, 33Smith Z. Shah R. Elmunzer B. et al.The next EPISOD: trends in utilization of endoscopic sphincterotomy for sphincter of Oddi dysfunction from 2010-2019.Clin Gastroenterol Hepatol. 2022; 20: e600-e609Abstract Full Text Full Text PDF PubMed Scopus (7) Google Scholar Difficult, prolonged, and/or traumatic cannulation, particularly if the PD is repeatedly injected or deeply accessed with a guidewire, is a leading risk factor for PEP.34Wang P. Li Z.S. Liu F. et al.Risk factors for ERCP-related complications: a prospective multicenter study.Am J Gastroenterol. 2009; 104: 31-40Crossref PubMed Scopus (352) Google Scholar Several new techniques and tools such as fully covered self-expanding metal stents have been associated with PEP and will need to be further evaluated in high-quality prospective studies.35Xia M.X. Zhou Y.F. Zhang M. et al.Influence of fully covered metal stenting on the risk of post-endoscopic retrograde cholangiopancreatography pancreatitis: a large multicenter study.J Gastroenterol Hepatol. 2020; 35: 2256-2263Crossref PubMed Scopus (13) Google Scholar Over time, the definition of "high risk" will need to be better defined. Given the evidence of efficacy to prevent PEP, increased cost-effectiveness, and minimal AEs, the panel strongly recommended prophylactic rectal NSAIDs in high-risk patients. The overall quality of the evidence was moderate. Recommendation 3: In unselected patients undergoing ERCP, the ASGE suggests wire-guided cannulation over contrast-guided cannulation to minimize the risk of PEP (Conditional recommendation/Moderate quality of evidence). Recommendation 3: In unselected patients undergoing ERCP, the ASGE suggests wire-guided cannulation over contrast-guided cannulation to minimize the risk of PEP (Conditional recommendation/Moderate quality of evidence). To address the question, we used a Cochrane meta-analysis that was updated by Tse et al36Tse 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 in parallel with the development of this guideline. Outcomes of interest included PEP, moderate PEP, and severe PEP as well as bleeding and perforation. Based on 15 randomized trials reporting on 4426 patients, guidewire-assisted access reduced PEP (relative risk [RR], .50; 95% CI, .31-0.72; I2 = 36%) relative to contrast-assisted access with no difference in AEs of postsphincterotomy bleeding or perforation. There was no difference in moderate (RR, .76; 95% CI, .38-1.52; I2 = 0) or severe (RR, .69; 95% CI, .27-1.81; I2 = 0) PEP. In 7 of 15 studies, pancreatic stents were used to prevent PEP at the endoscopist's discretion. PD stents were not permitted in 4 studies. Subgroup analysis revealed that guidewire-assisted approaches reduced PEP among trials that did not permit use of PD stents (RR, .24; 95% CI, .13-0.47; I2 = 0) but not for trials that allowed PD stent use (RR, .78; 95% CI, .42-1.18; I2 = 25). This would suggest that the cannulation technique may not be as relevant if a PD stent is placed. However, by the time an endoscopist has decided to place a PD stent, they have already achieved PD cannulation. Therefore, guidewire-assisted cannulation may still be preferable at the onset of the procedure. In 5 trials, the guidewire was passed through a sphincterotome already positioned in a duct to confirm whether it was biliary or pancreatic.37Lella F. Bagnolo F. Colombo E. et al.A simple way of avoiding post-ERCP pancreatitis.Gastrointest Endosc. 2004; 59: 830-834Abstract Full Text Full Text PDF PubMed Scopus (166) Google Scholar, 38Mangiavillano B. Mariani A. 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In our subanalysis, this significantly reduced PEP relative to contrast-assisted approaches (RR, .29; 95% CI, .18-.49; I2 = 0). In 6 trials, the guidewire was first passed into the duct followed by the sphincterotome.42Apostolopoulos P. Alexandrakis G. Liatsos C. et al.Guide wire-assisted selective access to the common bile duct could prevent post-ERCP pancreatitis.Endoscopy. 2005; 37: A278PubMed Google Scholar, 43Zhang Z. Li D. Liu J. et al.Randomize case-control study on decrease of post-ERCP pancreatitis by selective cannulation of common bile duct guided by guide wire.Chin J Dig Endosc. 2007; 24: 250-253Google Scholar,