post-ERCP Pancreatitis In High-risk Patients Research Articles

Indomethacin with or without prophylactic pancreatic stent placement to prevent pancreatitis after ERCP: a randomised non-inferiority trial

The combination of rectally administered indomethacin and placement of a prophylactic pancreatic stent is recommended to prevent pancreatitis after endoscopic retrograde cholangiopancreatography (ERCP) in high-risk patients. Preliminary evidence suggests that the use of indomethacin might eliminate or substantially reduce the need for stent placement, a technically complex, costly, and potentially harmful intervention. In this randomised, non-inferiority trial conducted at 20 referral centres in the USA and Canada, patients (aged ≥18 years) at high risk for post-ERCP pancreatitis were randomly assigned (1:1) to receive rectal indomethacin alone or the combination of indomethacin plus a prophylactic pancreatic stent. Patients, treating clinicians, and outcomes assessors were masked to study group assignment. The primary outcome was post-ERCP pancreatitis. To declare non-inferiority, the upper bound of the two-sided 95% CI for the difference in post-ERCP pancreatitis (indomethacin alone minus indomethacin plus stent) would have to be less than 5% (non-inferiority margin) in both the intention-to-treat and per-protocol populations. This trial is registered with ClinicalTrials.gov (NCT02476279), and is complete. Between Sept 17, 2015, and Jan 25, 2023, a total of 1950 patients were randomly assigned. Post-ERCP pancreatitis occurred in 145 (14·9%) of 975 patients in the indomethacin alone group and in 110 (11·3%) of 975 in the indomethacin plus stent group (risk difference 3·6%; 95% CI 0·6-6·6; p=0·18 for non-inferiority). A post-hoc intention-to-treat analysis of the risk difference between groups showed that indomethacin alone was inferior to the combination of indomethacin plus prophylactic stent (p=0·011). The relative benefit of stent placement was generally consistent across study subgroups but appeared more prominent among patients at highest risk for pancreatitis. Safety outcomes (serious adverse events, intensive care unit admission, and hospital length of stay) did not differ between groups. For preventing post-ERCP pancreatitis in high-risk patients, a strategy of indomethacin alone was not as effective as a strategy of indomethacin plus prophylactic pancreatic stent placement. These results support prophylactic pancreatic stent placement in addition to rectal indomethacin administration in high-risk patients, in accordance with clinical practice guidelines. US National Institutes of Health.

Nafamostat Reduces the Incidence of post-ERCP Pancreatitis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Pancreatitis is the most common complication of endoscopic retrograde cholangiopancreatography (ERCP). As the management of pancreatitis is limited, clinical approaches focus on the prevention of post-ERCP pancreatitis (PEP). In theory, the serine protease inhibitor nafamostat can reduce circulating inflammatory mediators in pancreatitis. We aimed to investigate the effect of nafamostat in the prevention of PEP in this systematic review and meta-analysis. The protocol for this review was registered in PROSPERO (CRD42022367988). We systematically searched 5 databases without any filters on September 26, 2022. The eligible population was adult patients undergoing ERCP. We compared the PEP preventive effect of nafamostat to placebo. The main outcome was the occurrence of PEP. We calculated the pooled odds ratios (ORs), mean differences, and corresponding 95% confidence intervals (95% CIs) and multilevel model. The risk of bias was assessed using the Rob2 tool. Seven randomized controlled trials involving 2,962 patients were eligible for inclusion. Nafamostat reduced the overall incidence rate of PEP (20 mg, OR: 0.50, 95% CI: 0.30-0.82 and 50 mg, OR: 0.48, 95% CI: 0.24-0.96). However, the occurrence of mild PEP was significantly reduced only in the subgroup receiving 20 mg nafamostat (OR, 0.49, 95% CI: 0.31-0.77). Overall, nafamostat therapy reduced moderate PEP in high-risk patients (OR: 0.18, 95% CI: 0.0.4-0.84) and mild PEP in low-risk patients (OR: 0.32, 95% CI: 0.17-0.61). Nafamostat is an effective therapy in the prevention of mild post-ERCP pancreatitis. Further research is required to determine the cost-effectiveness of this therapy.

Development and external validation of a nomogram for prediction of post-endoscopic retrograde cholangiopancreatography pancreatitis

Background and aimsEndoscopic retrograde cholangiopancreatography (ERCP) is widely performed for management of pancreatobiliary diseases; however, post-ERCP pancreatitis (PEP) remains as an unsolved problem. Although various risk factors for PEP have been reported, the prediction of PEP remains controversial. This study aimed to develop a predictive model for PEP. MethodsConsecutive patients undergoing ERCP for biliary indications at two centers were retrospectively studied. Using data from a training cohort, we utilized a multivariable model to select five variables to construct a nomogram. The predictive model was internally and externally validated. Based on the nomogram, the patients were categorized into low-, moderate-, and high-risk groups. ResultsUsing the data of 2224 patients in the training cohort, five variables were selected to generate a nomogram: 1) sex, 2) indication for ERCP, 3) difficult cannulation, 4) guidewire insertion into the pancreatic duct, and 5) endoscopic sphincterotomy or sphincteroplasty. The most significant risk factor was endoscopic papillary balloon dilation such as endoscopic sphincterotomy or sphincteroplasty. The bias-corrected concordance index was 0.72 in the training cohort and 0.72 in the validation cohort. Calibration curves for both cohorts demonstrated good agreement between the predicted and observed frequencies of the actual outcome. In the validation cohort, PEP developed in 5.0% and 14% of patients in the moderate- and high-risk groups, respectively. ConclusionsWe successfully developed a good predictive model for PEP. The prevention of PEP in high risk patients should be investigated further.

Efficacy of aggressive hydration with normal saline versus lactated Ringer's solution for the prevention of post-ERCP pancreatitis in high-risk patients: a randomized controlled trial.

Background and study aims Post-ERCP pancreatitis (PEP) is a common adverse event in high-risk patients. Current intervention known to reduce the incidence and severity of PEP include pancreatic duct stent placement, nonsteroidal anti-inflammatory drugs per rectum, and intravenous (IV) fluids. We compared aggressive normal saline (NS) vs aggressive lactated Ringer’s (LR) infusion for the prevention of PEP in high-risk patients undergoing ERCP. Patients and methods Patients were randomized to receive either an aggressive infusion of NS or LR. The infusion was started at a rate of 3 mL/kg/hr and continued throughout the ERCP procedure. A 20 mL/kg bolus was given at the end of the procedure, then continued at a rate of 3 mL/kg/hr. Results A total of 136 patients were included in our analysis. The incidence of PEP was 4 % (3/72 patients) in the LR group versus 11 % (7/64 patients) in the NS group resulting in a relative risk (RR) of 0.38 (95 % confidence interval [CI] 0.10 to 1.42; P = 0.19). The relative risk reduction (RRR) was 0.62 (95 % CI –0.41 to 0.90) along with an absolute risk reduction (ARR) of 0.07 (95 % CI –0.025 to 0.17) and an number needed to treat of 15 (95 % CI –41 to 6). Conclusions To our knowledge, this is the first study comparing aggressive IV NS to aggressive IV LR in high-risk patients. The incidence of PEP was lower in the group receiving an aggressive LR infusion (4 %) compared to NS infusion (11 %). However, the difference was not statistically significant likely due to poor accrual thereby impacting the power of the study.

Magnesium Sulfate for Prevention of Post-ERCP-Pancreatitis: A Randomized Controlled Trial.

Acute pancreatitis is one of the most common complications of endoscopic retrograde cholangiopancreatography (ERCP). Studies suggest that intrapancreatic calcium has an important role in activating pancreatic enzymes; in addition, elevated intraductal pressure is required for development of pancreatitis. Magnesium sulfate (MS), as a calcium antagonist and a muscle relaxant of the Oddi sphincter, is suggested to reduce the incidence and severity of post-ERCP-pancreatitis (PEP) in this article. We included 270 patients who referred for ERCP between March 2017 and March 2018. They were enrolled into MS (2 g) and placebo (normal saline) groups, administered 1 hour before and 6 hours after the procedure. The ERCPs were done by fellows of gastroenterology under supervision of expert physicians. The incidence and severity of PEP were followed. PEP was seen in 12 (8.9%) patients in the MS group and 17 (12.6%) in the placebo group (P value=0.33). The incidence of PEP in high risk patients group (P value=0.017). Although the usage of MS was not able to prevent PEP in all patients enrolled in this study, but it could significantly reduce the incidence of PEP in high risk patients of intervention group in comparison with placebo group. The median length of hospital stay was also significantly lower in new drug group in contrast to placebo.

S1005 Meta-Analysis and Systematic Review of Pancreatic Stents in Preventing Post-ERCP Pancreatitis

Introduction: Pancreatitis is a common and potentially devastating complication of ERCP. Prior studies have shown that prophylactic pancreatic duct stent (PS) placement may be effective to reduce post-ERCP pancreatitis (PEP) in high-risk patients, such as patients with sphincter of Oddi dysfunction or prior history of pancreatitis. However, prior meta-analyses are missing relevant studies both contemporaneously and since published. We aim to perform a comprehensive analysis comparing PS placement to no PS placement to prevent PEP in high-risk patients. Methods: In conjunction with a health sciences librarian, Ovid Medline, Embase and Embase Classic, Cochrane Library, and Web of Science were searched from inception to March 26, 2021. Randomized controlled trials that directly compared PS placement versus no PS placement in preventing PEP were included. Our primary outcome was the incidence of PEP. Additional outcomes included incidence of mild PEP, moderate PEP, and severe PEP, as well as the incidence of adverse outcomes including hemorrhage, infection, and pancreatic duct perforation. Quantitative data was harmonized using random effects models. Results: The search yielded 1,668 citations, 444 of which were removed as duplicates. Each study was assessed by two reviewers. 116 articles were selected for full text review, and eighteen randomized controlled trials were identified of pancreatic stent placement to prevent post-ERCP pancreatitis. In sum, 1,295 patients were assigned to pancreatic stent prophylaxis and 1,299 to no stent placement. There was a significant reduction in odds of PEP in the PS group (Figure 1, OR 0.36 [95% CI 0.28-0.46]). In addition, PS placement was strongly protective against severe pancreatitis (Table 1, OR 0.25 [95% CI 0.07-0.81]). Stent placement was successful in 98% of cases (95% CI 95-100) and there was no difference in pancreatic duct perforation, bleeding, or infection (Table 1). Conclusion: Pancreatic stent placement is an effective intervention to reduce the incidence of PEP in high-risk patients. Further, pancreatic stent placement is particularly effective against the severe forms of PEP. There is no significant difference in major non-pancreatitis adverse events for pancreatic stent placement compared to no stent placed.Figure 1.: a. Kaplan-Meier (KM) survival curves of time to hospital utilization for inpatients undergoing ERCP, stratified by ASGE 2011 complexity score Figure 1b. Post-hoc analysis of KM survival curve for inpatients undergoing ERCP, ASGE 2011 grade 1 versus 4 Figure 1c. Post-hoc analysis of KM survival curve for inpatients undergoing ERCP, ASGE 2011 grade 2 versus 4 Figure 1d. Post-hoc analysis of KM survival curve for inpatients undergoing ERCP, ASGE 2011 grade 3 versus 4.Table 1.: Odds Ratio of Major Outcomes With Pancreatic Stent Placement ERCP = endoscopic retrograde cholangiopancreatography, PS = pancreatic duct stent, OR = odds ratio, CI = confidence interval.

S1018 Rectal NSAIDs Decrease Post-ERCP Pancreatitis (PEP) in Unselected Patients - Comprehensive Meta-Analysis of Randomized Controlled Trials

Introduction: Endoscopic retrograde cholangiopancreatography (ERCP) is fundamental for treatment of pancreatico-biliary diseases, but results in PEP in up to 15% of patients. Phospholipase A2 (PLA2) is an important factor in the pancreatitis inflammatory cascade and NSAIDs, which inhibit PLA2 activity, prevent PEP in high-risk patients. We endeavored to identify and quantitatively synthesize the existing high-quality data to date on rectal NSAID use for the prevention of post ERCP pancreatitis in unselected patients without specific risk factors for PEP. Methods: In collaboration with a librarian, we searched the following databases: Ovid Medline (coverage 1946 – Present), Embase and Embase Classic (coverage 1947 – Present), Cochrane Library (coverage 1898-present), Web of Science (coverage 1900-present), Clinicaltrials.gov, and Google Scholar through April 2021. Using the Covidence system, two independent reviewers identified randomized controlled studies assessing rectal NSAIDs for PEP prevention in unselected patients. Our primary outcome was odds of developing PEP and our secondary outcome was odds of developing moderately severe or severe PEP. Pooled odds ratios were estimated using the random effects model. Results: After review of 504 abstracts and 234 full text documents, we identified 25 randomized controlled trials evaluating rectal NSAIDs for the prevention of PEP in unselected patients; 4071 patients received rectal NSAIDs and 4005 patients received a placebo. The most frequent NSAID used was diclofenac in 56% of studies, followed by indomethacin in 36%, ketoprofen in 4%, and naproxen in 4%. Unselected patients receiving rectal NSAIDs were less likely to develop PEP (OR 0.59, 95% CI 0.45-0.78) (Figure 1) as well as moderately severe and severe pancreatitis (OR 0.50, 95% CI 0.33-0.75). Conclusion: In unselected patients undergoing ERCP, rectal NSAID administration decreases the risk of post-ERCP pancreatitis and development of moderately severe or severe PEP. They should be considered for unselected patients undergoing ERCP, not simply those high risk for PEP.Figure 1.: Baseline characteristics and clinical outcomes in patients who has ERCP with glucagon (ERCP w glucagon, group 1) compared to individuals ERCP without glucagon (ERCP wo glucagon, group 2) Note: SD-Standard Deviation; € A 1:1 propensity score matching was done based on the following variables: age, gender, race, hypertension, diabetes mellitus, obesity, chronic kidney disease (CKD), Ischemic heart diseases (IHD), chronic obstructive pulmonary disease, indomethacin use, sphincter of Oddi dysfunction (SOD).

PREVENTION OF POST-ERCP PANCREATITIS IN HIGH-RISK PATIENTS

Aim. To study the efficacy of thoracic epidural analgesia (TEA) for the prevention of post-ERCP pancreatitis in high-risk patients. Materials and methods. A parallel, blinded, randomized study. The first (TEA group) group included patients (n = 98) in whom thoracic epidural analgesia was used during endoscopic transpapillary interventions (ETI), the second (OAI group) group included patients (n = 97) in whom opioid analgesics and indomethacin (per rectum). Results. The study showed that acute pancreatitis was diagnosed significantly less frequently in patients with the TEA group than in patients with the OAI group (p = 0.0135). If in the TEA group post-ERCP pancreatitis (PEP) was verified in 3.1% (3/98) patients, in the OAI group — in 12.4% (12/97) patients. When TEA was used in high risk patients of developing post-ERCP pancreatitis, its incidence decreased from 23.3% (10/43) to 4.4% (2/46) observations (p = 0.0095). Conclusion. The use of TEA is an effective and justified method of prevention in patients at high risk of developing post-ERCP pancreatitis. In patients with a low risk of developing this complication, the use of TEA is inappropriate due to the invasiveness of the method.

Pancreatic stent is the best tool to prevent post-ERCP pancreatitis in high-risk patients: Is the result from recent network meta-analysis valid?

Pancreatic stent is the best tool to prevent post-ERCP pancreatitis in high-risk patients: Is the result from recent network meta-analysis valid?

Real-World Practice Patterns in the Era of Rectal Indomethacin for Prophylaxis Against Post-ERCP Pancreatitis in a High-Risk Cohort.

The benefit of indomethacin suppositories for prophylaxis against post-ERCP pancreatitis (PEP) in high-risk patients was established in a landmark trial published in 2012. The aims of this study were to measure the adoption of indomethacin prophylaxis in widespread clinical practice, evaluate concurrent trends in pancreatic duct (PD) stent utilization, and estimate the impact of these changes on PEP in a high-risk population. Data were extracted from a commercial database (Explorys, IBM Watson Health, Somers, NY) that aggregates electronic health records from 26 US healthcare systems from 2009 to 2018. Using Systematized Nomenclature of Medicine Clinical Terms, we identified a cohort of patients who underwent endoscopic retrograde cholangiopancreatography (ERCP) and were at high risk for PEP based on narrow criteria. PEP was defined as an emergency department or hospital admission 1-5 days after ERCP with an associated diagnosis of pancreatitis. Twenty six thousand eight hundred twenty ERCPs were performed on this high-risk cohort from 2009 to 2018. The overall PEP rate during the study period was 8.6%. There was no decrease in PEP rates from 2012 to 2018. Beginning in 2012, indomethacin usage increased linearly (P < 0.001), but remained below 50% in 2018. As indomethacin increased, utilization of PD stents declined abruptly from 2013 to 2014 (40.7%-8.5%) and trended to a nadir of 3.0%. Despite its low cost, widespread availability, and level I evidence of benefit in reducing the risk of PEP in high-risk patients, the adoption of rectal indomethacin during ERCP has been slow and the medication continues to be under-utilized. In parallel, the PD stent usage has declined dramatically. The lack of change in PEP rates during the study period could be attributable to the persistent low usage of rectal indomethacin or the decline in PD stent use. Further educational efforts and quality assurance measures are warranted to ensure that rectal indomethacin and PD stent placement are more appropriately used in clinical practice.

Comparative effectiveness of pharmacologic and endoscopic interventions for prevention of post-ERCP pancreatitis: a network meta-analysis.

Background and study aims While several interventions may decrease risk of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis, it remains unclear whether one strategy is superior to others. The purpose of this study was to compare the effectiveness of pharmacologic and endoscopic interventions to prevent post-ERCP pancreatitis among high-risk patients. Methods A systematic review was performed to identify randomized controlled trials from PubMed, Embase, Web of Science, and Cochrane database through May 2017. Interventions included: rectal non-steroidal anti-inflammatory drugs (NSAIDs), aggressive hydration with lactated ringerʼs (LR) solution, and pancreatic stent placement compared to placebo. Only studies with patients at high-risk for post-ERCP pancreatitis were included. Bayesian network meta-analysis was performed and relative ranking of treatments was assessed using surface under the cumulative ranking (SUCRA) probabilities. Results We identified 29 trials, comprising 7,862 participants comparing four preventive strategies. On network meta-analysis, compared with placebo, rectal NSAIDs (B = – 0.69, 95 % CI [–1.18; – 0.21]), pancreatic stent (B = – 1.25, 95 % CI [–1.81 to –0.69]), LR (B = – 0.67, 95 % CI [–1.20 to –0.13]), and combination of LR plus rectal NSAIDs (B = – 1.58; 95 % CI [–3.0 to –0.17]), were all associated with a reduced risk of post-ERCP pancreatitis. Pancreatic stent placement had the highest SUCRA probability (0.81, 95 % CI [0.83 to 0.80]) of being ranked the best prophylactic treatment. Conclusions Based on this network meta-analysis, pancreatic stent placement appears to be the most effective preventive strategy for post-ERCP pancreatitis in high-risk patients.

Risk factors of post-ERCP pancreatitis in high-risk patients despite prevention with prophylactic pancreatic stents

Objectives: To analyze risk factors of post-ERCP pancreatitis (PEP) in high risk patients in whom prophylactic pancreatic stents (PPSs) were intended to use to prevent endoscopic retrograde cholangiography (ERCP)-related complications.Patients and methods: Three hundred and seventeen high-risk patients for developing PEP were considered for preventive pancreatic stent placement in our endoscopy unit over 5 years. 5 Fr, 3–5 cm long PPSs were used. All data were collected in a predefined database. Development of PEP despite PPS placement was analyzed.Results: PEP occurred in 29 of 288 successfully stented patients (10.07%; 24 mild, four moderate, one severe). PPS was protective against all risks factors except for sphincter of Oddi dysfunction (SOD). PPS related complication rate was 2.78% (n = 8). Unsuccessful stenting occurred in 29 patients (9.15%), PEP developed in 41.38% (n = 12; seven mild, four moderate, one severe). Those patients who had more patient related risk factors were more likely to develop PEP despite preventive measures with PPS. On the contrary, PPS placement was less successful in patients who had more procedure related risk factors.Conclusions: PPS is protective against all risks factors of PEP except for SOD in high-risk patients. More vulnerable patients who have more patient-related risk factors are more likely to develop PEP despite PPS is used, while more complex procedures predispose to unsuccessful PPS placement in patients with more procedure-related risk factors. PPS insertion in high-risk patients is effective and safe preventive method and the procedure related complication rate is reasonably low.

Low-dose rectal diclofenac does not prevent post-ERCP pancreatitis in low- or high-risk patients.

The most common adverse event following an endoscopic retrograde cholangiopancreatography (ERCP) procedure is post-ERCP pancreatitis (PEP). Rectal nonsteroidal anti-inflammatory drug (NSAID) administration has shown promise to reduce the risk of PEP in high-risk patients. However, in contrast to high-risk patients, the role of NSAID administration in patients with low risk remains controversial. We performed a prospective, single-center, single-blinded, two-arm parallel group, randomized controlled trial to clarify the efficacy of low dose (50mg) rectal NSAID administration for preventing PEP in at-risk patients. Patients scheduled to undergo ERCP were randomized into two groups, those with and without rectal administration of diclofenac. Patients in the diclofenac group received 50mg of rectal diclofenac 30min before undergoing ERCP. The primary endpoint was rate of PEP. A total of 303 were randomized into the study groups. Four patients declined participation following randomization, and another two were withdrawn. As a result, a total of 147 patients were assigned to the diclofenac group and 150 to the control group. The baseline and procedural characteristics were similar in both groups. The primary endpoint of PEP occurrence was seen in 13 of 297 patients (4.4%), including eight (5.4%) in the diclofenac group and five (3.3%) in the control group (P=0.286). Additionally, those results were not significantly different when patients were classified as low or high risk. Prophylactic low-dose rectal diclofenac did not reduce the incidence of PEP following ERCP in patients classified as low or high risk.

7 cm vs. 5 cm Pancreatic Stents for the Prevention of Post-ERCP Pancreatitis in High-risk Patients

7 cm vs. 5 cm Pancreatic Stents for the Prevention of Post-ERCP Pancreatitis in High-risk Patients

78 What Is the Impact of a Delayed Presentation on Outpatients With Post-ERCP Pancreatitis? An Analysis of Clinical Predictors and Outcomes

INTRODUCTION: Post-ERCP pancreatitis (PEP) occurs in up to 15% of high risk patients. Symptoms after ERCP are common and usually determine admission. However, discharge of outpatients at risk for PEP is frequent after ERCP. In retrospective studies, discharged PEP patients are at increased risk for severity, possibly due to delays in IV fluid therapy. The aim of this study is to evaluate clinical predictors and outcomes in patients discharged and later admitted with delayed presentation of PEP. METHODS: We identified consecutive outpatients with PEP enrolled in a prospective study designed to evaluate the optimal rectal Indomethacin dose for prevention of PEP in high-risk patients. All patients received Indomethacin and were observed for at least 4 hours post-ERCP per protocol. All clinical data except IV fluids, recovery medications, and pain scores were collected prospectively. Diagnosis and severity of PEP was defined by Cotton criteria. RESULTS: 107/720 (14.9%) developed PEP. 135/720 (18.8%) were directly admitted after ERCP. While the direct admission rate in patients that developed PEP was higher (P &lt; 0.001), 58/107 (54.2%) were discharged and had a delayed presentation of PEP. Median time to presentation was 24 hours (IQR 15–31.75 h). Discharged patients were older (age 47.7 vs 41.1, P = 0.026), more often had a morning procedure (59.2% vs 39.7%, P = 0.044), less often had pancreatic stent placement (82.8% vs 95.9%, P = 0.032), spent less time in recovery (261 vs 312 minutes, P = 0.004), required less IV opioids (6.4 vs 17.3 MME, P &lt; 0.001) and had lower pain scores (2.8 vs 6.5, P &lt; 0.001) (Table 1). On multivariable analysis, an afternoon procedure (OR 4.00, P = 0.016) and pain score &gt;3 (OR 1.37, P = 0.001) were associated with admission. While discharged patients were more likely to present with SIRS on admission (43.1% vs 10.2%, P &lt; 0.001), a delayed presentation was not associated with severe PEP (Table 2). CONCLUSION: Delayed presentation of PEP after discharge of high-risk patients is frequent, but not associated with adverse outcomes or severe PEP. Systematic deployment of PEP prophylaxis with rectal Indomethacin, pancreatic stents, and IV fluids may attenuate the impact of delayed presentation on outcomes. Afternoon procedure time and increased pain appear to influence decisions to admit. However, given the frequency of delayed presentation of PEP, accurate and early diagnostic tests for PEP may be of clinical value.

Risk Factors for Post-ERCP Pancreatitis in High-Risk Patients Receiving Post-procedure Rectal Indomethacin

BackgroundPost-ERCP pancreatitis (PEP) is the most common adverse event of ERCP. Rectal indomethacin has been widely administered to decrease the incidence of PEP in high-risk patients. However, it cannot completely prevent the occurrence of PEP. The purpose of the study was to evaluate the risk factors for PEP in high-risk patients receiving post-ERCP indomethacin. MethodsFrom June 2012 to July 2015, patients undergoing ERCP and at high risk for PEP in three tertiary hospitals in China were enrolled. All patients received indomethacin after the procedure. Patient-related and procedure-related risk factors for PEP were collected. Logistic regression analysis was used to investigate the risk factors. ResultsSeven hundred ninety patients at high risk for PEP received post-ERCP indomethacin. The incidence of overall PEP and moderate-to-severe PEP was 8.0 and 1.5%, respectively. In multivariate analysis, suspected sphincter of Oddi dysfunction (SOD) (OR 2.73; 95%CI 1.38–5.43; p = 0.004), the presence of hilar obstruction (OR 4.53; 95%CI 1.60–12.81; p = 0.004), number of cannulation attempts ≥ 13 (OR 2.00; 95%CI 1.07–3.77; p = 0.030), inadvertent pancreatic duct (PD) cannulation ≥ 1 (OR 2.26; 95%CI 1.04–4.90; p = 0.040), and pancreatic contrast injections ≥ 1 (OR 2.30; 95%CI 1.02–5.23; p = 0.046) were high risk factors for overall PEP. For moderate-to-severe PEP, suspected SOD (OR 4.67; 1.19–18.35; p = 0.027), the presence of hilar obstruction (OR 7.95; 1.39–44.97; p = 0.010), and more cannulation attempts (OR 3.71; 1.09–12.65; p = 0.036) were three independent risk factors. ConclusionsA substantial number of high-risk patients had PEP even receiving post-ERCP rectal indomethacin. The independent risk factors included suspected SOD, hilar stricture, more cannulation attempts, inadvertent PD cannulation, and PD contrast injections. Trial RegistrationNCT02709421

Interventional Endoscopy.

Introduction: Rectal indomethacin and papillary spray of epinephrine have separately shown efficacy for the prevention of post-ERCP pancreatitis (PEP) in randomized controlled trials. We hypothesized that the combination of papillary spray of epinephrine and indomethacin may further reduce PEP over indomethacin alone. Methods: We conducted a comparative effectiveness, multicenter, double-blind, randomized trial comparing rectal indomethacin alone versus a combination of papillary spray of epinephrine and rectal indomethacin for the prevention of PEP in high risk patients. Patients with suspected sphincter of Oddi dysfunction (SOD) type 3 and those who received a pancreatic stent were excluded. Patients were randomized to receive either 100 mg of indomethacin and papillary spray of 20 mL of normal saline (indomethacin alone group) or 100 mg of indomethacin and papillary spray of 20 mL of 0.02% epinephrine (combination group) at the end of ERCP. A Data and Safety Monitoring Board conducted interim analyses with prespecified stopping rules. The primary outcome was the incidence of PEP and the secondary outcome was the severity of PEP, both defined by the consensus criteria. A total of 948 patients (474 in each group) would provide a power of 80% at a 2-sided significance level of 5% to detect a 50% difference in the rates of PEP, assuming PEP rates of 10% and 5%, respectively, for rectal indomethacin and the combination. A two-tailed Fisher's exact test was used to analyze the difference in the proportion of patients with PEP in the indomethacin alone versus the combination group. Results: A total 959 of patients (mean age 52.33±14.96 years; 551 (57.4%) females) were randomized for this trial. The baseline demographic and clinical characteristics were similar between the two groups. Females < 50 years of age (25.4%) and difficult cannulation (84.9%) were the most common patient and procedural risk factors, respectively. Trainees were involved in 24% of the cases. The incidence of PEP was 6.4% in the indomethacin alone group (n=482) compared to 6.7% in the combination group (n=477) (p=0.87). Severe PEP was found in 5 (12%) versus 7 (16%) patients in the indomethacin alone and combination groups, respectively (p=0.88). The overall mortality was 0.6% which was unrelated to the primary outcome. Conclusion: The combination of papillary spray of epinephrine and rectal indomethacin does not reduce the incidence of PEP compared to rectal indomethacin alone in high risk patients.FigureTable: Table. Association of risk factors with the incidence of PEP

Periprocedural Fluid Type and Volume Reduce the Risk of Post-ERCP Pancreatitis in High-Risk Patients: A Secondary Analysis of a Randomized Controlled Trial: 2017 ACG Governors Award for Excellence in Clinical Research

Introduction: Aggressive hydration with lactated Ringer's was recently shown to be efficacious in reducing the incidence of post-ERCP pancreatitis (PEP) in a randomized controlled trial (RCT) of average risk patients undergoing ERCP. The impact of fluid on the incidence of PEP has not been evaluated in high risk patients. Methods: We conducted a secondary analysis of the effect of volume and type of intravenous fluid administered on the incidence of PEP in high risk patients who underwent ERCP as a part of a double blinded RCT comparing the efficacy of rectal indomethacin versus a combination of papillary spray of epinephrine and rectal indomethacin for the prevention of PEP. High risk patients were defined on the basis of prospectively validated patient and procedure-related risk factors. Patients who underwent planned therapeutic pancreatic stenting and those with suspected sphincter of Oddi dysfunction (SOD) type 3 were excluded from the study. PEP was defined as per the consensus criteria. The volume and type of fluid(s) infused during and after ERCP (periprocedural) were evaluated for their impact on the incidence of PEP using univariable logistic regression analysis. Results: A total 959 patients (mean age of 52.33±14.96 years; 551 (57.4%) females) were randomized during the trial, of whom 476 (49.6%) received periprocedural fluids (mean fluid administered 1245±629mL). The incidence of PEP was reduced in patients who received periprocedural fluid vs those who did not receive periprocedural fluid (5.2% vs 8.0%, P=0.079; OR, 0.65; 95% CI 0.38-1.09). Patients who developed PEP received a lower mean volume of fluid compared to those who did not develop PEP (752±783mL vs. 1012±725mL, P=0.036). There were 174 patients (37%) who received lactated Ringer's (LR). Patients who developed PEP received a lower mean volume of LR compared to those who did not develop PEP (329±356 vs. 570±559mL, P=0.006). The use of LR was associated with a lower risk of PEP compared to those who received all other types of fluid (5.8% vs 9.8%, P=0.047; OR, 0.56; 95% CI 0.31-0.99, P=0.047). Conclusion: Higher mean volume of periprocedural fluids and use of lactated Ringer's solution further reduces the incidence of post-ERCP pancreatitis beyond rectal indomethacin based on this subgroup analysis of a pharmacological prophylaxis PEP trial conducted in high risk patients.Table: No Caption available.

How to select patients and timing for rectal indomethacin to prevent post-ERCP pancreatitis: a systematic review and meta-analysis

BackgroundAcute pancreatitis is a severe complication of endoscopic retrograde cholangiopancreatography (ERCP). Previous meta-analyses have shown that indomethacin effectively prevents this complication; however, the data are limited. We performed a systematic review and meta-analysis to clarify the applications for rectal indomethacin.MethodsA systematic search was performed in June 2016. Human prospective, randomized, placebo-controlled trials that compared rectally administered indomethacin with a placebo for the prevention of post-ERCP pancreatitis (PEP) were included. A meta-analysis was performed using a random-effects model to assess the outcomes (PEP) using Review Manager 5.0.ResultsSeven randomized controlled trials met the inclusion criteria (n = 3013). The overall incidence of PEP was significantly lower after prophylactic administration of rectal indomethacin than after administration of the placebo (RR, 0.58, 95% CI, 0.40–0.83; P = 0.004). A subgroup analysis was performed for rectal indomethacin administration compared to a placebo in high-risk patients (RR, 0.46; 95% CI, 0.32–0.65; P < 0.00001) and average-risk patients (RR, 0.75; 95% CI, 0.46–1.22; P = 0.25) and for administration before ERCP (RR, 0.56; 95% CI, 0.39–0.79; P = 0.001) and after the procedure (RR, 0.61; 95% CI, 0.26–1.44; P = 0.26).ConclusionsThis meta-analysis indicated that prophylactic rectal indomethacin is not suitable for all patients undergoing ERCP but it is safe and effective to prevent PEP in high-risk patients. In addition, rectal indomethacin administration before ERCP is superior to its administration after ERCP for the prevention of PEP.

Intravenous injection of low-dose flurbiprofen axetil for preventing post-ERCP pancreatitis in high-risk patients: An interim analysis of the trial

Background and study aims: Several meta-analyses and randomized control trials have demonstrated the efficacy of rectal nonsteroidal anti-inflammatory drugs for preventing post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP). Diclofenac or indomethacin was administered at a dose of 100 mg in those studies, which may be too high for Asian population. In addition, rectal administration can be considered complicated. Patients and methods: This study was a prospective, randomized, placebo-controlled trial. Patients with a PEP risk score ≥ 1 were randomly assigned to receive intravenous injection of 50 mg flurbiprofen axetil (flurbiprofen group) or saline only (placebo group). The primary outcome was reduced PEP. The secondary outcome was amylase level after 2 hours of ERCP as a predictor of PEP. (Clinical Trials.gov, ID UMIN000011322) Results: In total, 144 patients were enrolled from August 2013 to March 2015. We performed an interim analysis of the first 100 patients: 47 received flurbiprofen axetil and 53 received placebo. PEP occurred in 11 patients (11 %): 2 of 47 (4.3 %) in the flurbiprofen group and 9 of 53 (17 %) in the placebo group (P = 0.042). Relative risk reduction was 62.4 %. Hyperamylasemia did not differ significantly (17.0 % vs. 26.4 %, P = 0.109). This analysis resulted in early termination of the study for ethical reasons. Conclusions: Intravenous injection of low-dose flurbiprofen axetil after ERCP can reduce the incidence of PEP in high-risk patients