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.

The role of rectal diclofenac and aggressive hydration with Ringer's lactate in preventing post-endoscopic retrograde cholangiopancreatography pancreatitis in high-risk patients

The role of rectal diclofenac and aggressive hydration with Ringer's lactate in preventing post-endoscopic retrograde cholangiopancreatography pancreatitis in high-risk patients

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.

The Latest Knowledge on Endoscopic Retrograde Cholangiopancreatography-related Pancreatitis

ERCP has been established as a golden diagnostic and therapeutic modality in various pancreatobiliary diseases, including gallstones and malignancy. On the other hand, ERCP is a relatively invasive procedure with radiation hazards and major complications. Among the major complications, ERCP-related pancreatitis has been reported in more than 14.7% of high-risk patients, which might lead to extended hospitalization and a substantial burden for both patients and physicians. Recent guidelines have defined the high-risk factors for ERCP-related pancreatitis. In addition, several outstanding studies have shown that rectal non-steroidal anti-inflammatory drugs, aggressive hydration with lactated Ringer's solution, and pancreatic stents can reduce ERCP-related pancreatitis in high-risk patients or all patients. A prevention algorithm for ERCP-related pancreatitis was provided based on advanced research.

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.

Effect of Adding Intravenous Somatostatin to Rectal Indomethacin on Post-Endoscopic Retrograde Cholangiopancreatography (ERCP) Pancreatitis in High-risk Patients: A Double-blind Randomized Placebo-controlled Clinical Trial.

Endoscopic retrograde cholangiopancreatography (ERCP) has an important role in the treatment of pancreaticobiliary disorders. Considering the high prevalence and importance of postendoscopic retrograde cholangiopancreatography pancreatitis (PEP) and the controversial findings, we aimed to determine the effect of adding intravenous somatostatin to rectal indomethacin on the incidence of PEP in high-risk patients. In this prospective study, 530 patients underwent ERCP during March 2018 and February 2019. Patients were randomized into 2 groups. The intervention group received a bolus injection of 250 μg somatostatin followed by an infusion of 500 μg of somatostatin for 2 hours. In both groups, 100 mg of pre-ERCP suppository indomethacin was administrated. All patients were screened for PEP symptoms and signs for 24 hours after ERCP (Iranian Registry of Clinical Trials code: IRCT20080921001264N11). A total of 376 patients were finally analyzed. PEP was the most common adverse event with 50 (13.2%) episodes, including 21 (5.5%) mild, 23 (6.1%) moderate, and 6 (1.2%) severe. The rate of PEP was 15.2% in the control group and 11.4% in the intervention group ( P =0.666). The incidence of post-ERCP hyperamylasemia was 21.7% in the control group and 18.2% in the intervention group ( P =0.395). No death occurred. In this study administration of somatostatin plus indomethacin could safely reduce the rate of post-ERCP hyperamylasemia and PEP in the intervention group compared with the control group, but the differences were not significant. Further studies with larger sample sizes are required.

Rectal nonsteroidal anti-inflammatory drugs and pancreatic stents in preventing post-endoscopic retrograde cholangiopancreatography pancreatitis in high-risk patients: A network meta-analysis.

Background:100 mg rectal nonsteroidal anti-inflammatory drugs (NSAIDs) and pancreatic stents both significantly reduce the incidence of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis. Direct comparison of randomized controlled trials (RCTs) between them in high-risk patients is absent. We conducted this network meta-analysis to indirectly compare the efficacies of 100 mg rectal NSAIDs and pancreatic stents in preventing post-ERCP pancreatitis (PEP) in high-risk patients and help us decide which is preferred in clinical practice.Methods:A comprehensive search was done to identify RCTs published in English full-text. Interventions included 100 mg rectal NSAIDs (diclofenac or indomethacin) and pancreatic stents. Only studies with high-risk patients of PEP were included. Meta-analyses of NSAIDs and pancreatic stents were conducted respectively. A network meta-analysis using the Bayesian method was performed.Results:We included 14 RCTs, 8 on pancreatic stents and 6 on 100 mg rectal NSAIDs in high-risk patients. There was no direct comparison between them. After excluding an outlier study on NSAIDs (n = 144), meta-analyses showed they both significantly and statistically reduced the incidence of PEP in high-risk patients (pancreatic stents: n = 8 studies, random-effects risk ratio (RR)0.41, 95%CI 0.30–0.56, I2 = 0%; NSAIDs: n = 5 studies, random-effects RR 0.37, 95%CI 0.25–0.54, I2 = 0%). And network meta-analysis showed efficacy of 100 mg rectal NSAIDs was equal to pancreatic stents (random-effects RR 0.94, 95%CI 0.50–1.8).Conclusions:The efficacy of 100 mg rectal NSAIDs (diclofenac or indomethacin) seems equally significant to pancreatic stents in preventing PEP in high-risk patients. Considering the cost-effectiveness and safety, 100 mg diclofenac or indomethacin may be preferred.

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?

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.

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

Video Comment on Rasoul Sotoudehmanesh et al.

Rasoul Sotoudehmanesh et al. Pharmacological prophylaxis versus pancreatic duct stenting plus pharmacological prophylaxis for prevention of post-ERCP pancreatitis in high risk patients: a randomized trial

A Randomized Trial of Topical Epinephrine and Rectal Indomethacin for Preventing Post-Endoscopic Retrograde Cholangiopancreatography Pancreatitis in High-Risk Patients.

Rectal indomethacin and topical spray of epinephrine have separately shown efficacy in the prevention of post-endoscopic retrograde cholangiopancreatography pancreatitis (PEP) in randomized controlled trials. We hypothesized that the combination of indomethacin and topical spray of epinephrine on the duodenal papillae would further reduce PEP than when indomethacin was used alone. We conducted a comparative effectiveness, multicenter, double-blinded, randomized trial of rectal indomethacin alone vs a combination of rectal indomethacin and topical spray of epinephrine for the prevention of PEP in high-risk patients. The primary outcome was the incidence of PEP and the secondary outcome was the severity of PEP. A 2-tailed Fisher's exact test was used to analyze the difference in the proportion of patients with PEP in the indomethacin alone vs the combination group. A total of 960 patients (mean age 52.33 ± 14.96 years; 551 [57.4%] females) were randomized and 959 completed follow-up. The baseline demographic and clinical characteristics were similar between the 2 groups. Women <50 years of age (25.4%) and difficult cannulation (84.9%) were the most common PEP risk factors. 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%) and 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. The combination of rectal indomethacin and topical spray of epinephrine does not reduce the incidence of PEP compared to rectal indomethacin alone in high-risk patients; https://clinicaltrials.gov/ct2/show/NCT02116309.

Modified prophylactic 5-fr pancreatic duct stent enhances the rate of spontaneous dislodgement: A multicenter randomized controlled trial.

Prophylactic pancreatic duct stent placement effectively reduces post-endoscopic retrograde cholangiopancreatography pancreatitis in high-risk patients, but the optimal stent remains unclear. We modified a 5-Fr, 3 cm pancreatic stent by removing the flange on the pancreatic side and compared the rate of spontaneous dislodgement and complications with the ordinary stent. This was a randomized controlled trial at six tertiary endoscopic centers. Patients deemed high risk for post-endoscopic retrograde cholangiopancreatography pancreatitis randomly received modified or ordinary pancreatic stent. The primary outcome was spontaneous stent dislodgement at five days and 14 days. Secondary outcomes were the success rate of stent placement and complications. A total of 276 patients were randomly assigned to receive modified stents (mS group) and ordinary stents (oS group). The placement of a pancreatic stent was successful in all 276 patients. There were no significant differences between groups with respect to age, sex, major diagnosis, or indications for stenting. At five days the spontaneous dislodgement rate was 47.72% for the mS group and 15.67% for the oS group (p<0.001); at 14 days the rates were 84.21% and 42.65%, respectively (p < 0.001). Post-endoscopic retrograde cholangiopancreatography pancreatitis occurred in 6.52% of all patients. There were no significant differences regarding the incidences of post-endoscopic retrograde cholangiopancreatography pancreatitis, hemorrhage or fever. The modified short 5-Fr stent has a higher spontaneous dislodgement rate than ordinary pancreatic stent, thus obviating the need for endoscopic removal. The modified pancreatic stent does not increase the incidence of post-endoscopic retrograde cholangiopancreatography pancreatitis or other complications. The endoscopist can consider removing the flange on the pancreatic duct side for prophylactic pancreatic duct manipulation.

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

Rectal diclofenac does not prevent post-ERCP pancreatitis in consecutive high-risk and low-risk patients.

rectal diclofenac is a nonsteroidal anti-inflammatory drug (NSAID) that is used to prevent pancreatitis in high-risk patients during endoscopic retrograde cholangiopancreatography (ERCP). The European Society of Gastrointestinal Endoscopy (ESGE) recommends the use of prophylaxis with indomethacin or diclofenac in all patients undergoing ERCP, including those at low or intermediate risk of pancreatitis. A study to investigate the efficacy of this recommendation was performed. this was a mixed cohort study. A total of 1,512 ERCP procedures performed in our institution from January 2009 to July 2016 were included in the study. Until June 2012, 718 patients did not receive diclofenac. Subsequently, 794 patients without contraindications received 100 mg of rectal diclofenac at the onset of the procedure. Risk factors for post-ERCP pancreatitis (PEAP) and PEAP cases defined using consensus criteria were recorded. a total of 47 PEAP events (3.1%) were reported, 3.4% in the diclofenac group and 2.8% in the non-diclofenac group (p = 0.554); 26.1% of patients had risk factors for PEAP. In the diclofenac group, PEAP developed in 4.4%, 0.5% and 2.6% of subjects with intact papillae, prior sphincterotomy and extended sphincterotomy, respectively. The results were similar for the non-diclofenac group: 4% with intact papillae, 0.9% with prior sphincterotomy, and 2.5% with extended sphincterotomy, respectively. PEAP severity was similar in both groups. rectal diclofenac before ERCP did not prevent the development of post-ERCP acute pancreatitis in non-selected consecutive patients.

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.

541 A Randomized Trial of Rectal Indomethacin and Papillary Spray of Epinephrine Versus Rectal Indomethacin Alone for the Prevention of Post-Ercp Pancreatitis in High Risk Patients

541 A Randomized Trial of Rectal Indomethacin and Papillary Spray of Epinephrine Versus Rectal Indomethacin Alone for the Prevention of Post-Ercp Pancreatitis in High Risk Patients

Sa1371 Periprocedural Fluid Type and Volume Reduce the Risk of Post-ERCP Pancreatitis in High Risk Patients: A Secondary Analysis of a Randomized Controlled Trial

Sa1371 Periprocedural Fluid Type and Volume Reduce the Risk of Post-ERCP Pancreatitis in High Risk Patients: A Secondary Analysis of a Randomized Controlled Trial

Sa1386 Risk Factors for Post-Endoscopic Retrograde Cholangiopancreatography (ERCP) Pancreatitis in High-Risk Patients: Secondary Analysis of a Randomized Controlled Study

Sa1386 Risk Factors for Post-Endoscopic Retrograde Cholangiopancreatography (ERCP) Pancreatitis in High-Risk Patients: Secondary Analysis of a Randomized Controlled Study