Rectal Nonsteroidal Anti-inflammatory Drugs Research Articles

Combination of Somatostatin and Rectal Nonsteroidal Anti-Inflammatory Drugs for Prevention of Postendoscopic Retrograde Cholangiopancreatography Pancreatitis in High-Risk Patients: A Meta-Analysis of Randomized Controlled Trials.

Combination of Somatostatin and Rectal Nonsteroidal Anti-Inflammatory Drugs for Prevention of Postendoscopic Retrograde Cholangiopancreatography Pancreatitis in High-Risk Patients: A Meta-Analysis of Randomized Controlled Trials.

Development and validation of a machine learning–based, point-of-care risk calculator for post-ERCP pancreatitis and prophylaxis selection

A robust model of post-ERCP pancreatitis (PEP) risk is not currently available. We aimed to develop a machine learning-based tool for PEP risk prediction to aid in clinical decision making related to periprocedural prophylaxis selection and postprocedural monitoring. Feature selection, model training, and validation were performed using patient-level data from 12 randomized controlled trials. A gradient-boosted machine (GBM) model was trained to estimate PEP risk, and the performance of the resulting model was evaluated using the area under the receiver operating curve (AUC) with 5-fold cross-validation. A web-based clinical decision-making tool was created, and a prospective pilot study was performed using data from ERCPs performed at the Johns Hopkins Hospital over a 1-month period. A total of 7389 patients were included in the GBM with an 8.6% rate of PEP. The model was trained on 20 PEP risk factors and 5 prophylactic interventions (rectal nonsteroidal anti-inflammatory drugs [NSAIDs], aggressive hydration, combined rectal NSAIDs and aggressive hydration, pancreatic duct stenting, and combined rectal NSAIDs and pancreatic duct stenting). The resulting GBM model had an AUC of 0.70 (65% specificity, 65% sensitivity, 95% negative predictive value, and 15% positive predictive value). A total of 135 patients were included in the prospective pilot study, resulting in an AUC of 0.74. This study demonstrates the feasibility and utility of a novel machine learning-based PEP risk estimation tool with high negative predictive value to aid in prophylaxis selection and identify patients at low risk who may not require extended postprocedure monitoring.

Post-endoscopic retrograde cholangiopancreatography pancreatitis: a review

Endoscopic retrograde cholangiopancreatography (ERCP) has continued to develop over recent decades with regard to both indications for its use and improvements in technique. The most common complication is post-ERCP pancreatitis (PEP) with incidence rates being reported at ~10%. The exact mechanism of PEP is unknown but is likely multifactorial with papillary edema contributing to the activation of the inflammatory cascade playing an important role. Selected risk factors include patient-related factors (female sex, younger age, sphincter of Oddi dysfunction, and history of PEP) and procedure-related factors (difficult cannulation, multiple pancreatic duct guidewire passes, pancreatic acinarization, multiple pancreatic duct contrast injections, and precut sphincterotomy). Several preventative prophylactic strategies have been posited; however, current guidelines recommend the use of rectal non-steroidal anti-inflammatory drugs (NSAIDs), aggressive intravenous (IV) fluid hydration, and pancreatic duct stents. Appropriate patient selection and the use of noninvasive imaging modalities for diagnosis of pancreaticobiliary abnormalities is a key aspect in prevention. Future studies continue to explore various pharmacologic, procedure-related, and combination strategies for prevention and will be important as the use of ERCP continues to grow.

Pharmacological and non-pharmacological prophylaxis in the prevention of post-endoscopic retrograde cholangiopancreatography pancreatitis: a narrative review

Endoscopic retrograde cholangiopancreatography is a diagnostic and therapeutic procedure for various gastrointestinal problems. Pancreatitis is a severe complication of the procedure. The main objective of this study was to address if post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis can be prevented and what are the various pharmacological and non-pharmacological options along with their efficacy. Keywords “post-ERCP” and “pancreatitis” were used to search articles in Pubmed. Randomized controlled trials on patients undergoing ERCP due to any disease using pharmacological or non-pharmacological intervention published in the last 7 years were included. Observational studies, descriptive studies, reviews, and studies with no full access were excluded. The primary outcome in the trials was a frequency of post-ERCP pancreatitis. Non-steroidal anti-inflammatory drugs (NSAIDs) were the most effective drugs in reducing the incidence of pancreatitis. The preferred route was rectal. After NSAIDs, intravenous hydration and sublingual nitrate showed promising outcomes, especially when combined with rectal NSAIDs. Other drugs like magnesium sulfate and nafamostat mesilate did reduce the incidence, but the results were not statistically significant. Epinephrine spray on duodenal papilla showed no benefits and instead had a risk of increasing the incidence. Stent placement also reduced the incidence of pancreatitis. In conclusion, rectal NSAIDs alone or combined with IV hydration and sublingual nitrate significantly reduced the incidence of pancreatitis, and stent placement was comparable to pharmacological interventions. Thus, regular use of pharmacological interventions before the procedure can help to reduce the incidence of this grave complication.

Endoscopic retrograde cholangiopancreatography-related complications: risk stratification, prevention, and management.

Endoscopic retrograde cholangiopancreatography (ERCP) plays a crucial role in the management of pancreaticobiliary disorders. Although the ERCP technique has been refined over the past five decades, it remains one of the endoscopic procedures with the highest rate of complications. Risk factors for ERCP-related complications are broadly classified into patient-, procedure-, and operator-related risk factors. Although non-modifiable, patient-related risk factors allow for the closer monitoring and instatement of preventive measures. Post-ERCP pancreatitis is the most common complication of ERCP. Risk reduction strategies include intravenous hydration, rectal nonsteroidal anti-inflammatory drugs, and pancreatic stent placement in selected patients. Perforation is associated with significant morbidity and mortality, and prompt recognition and treatment of ERCP-related perforations are key to ensuring good clinical outcomes. Endoscopy plays an expanding role in the treatment of perforations. Specific management strategies depend on the location of the perforation and the patient's clinical status. The risk of post-ERCP bleeding can be attenuated by preprocedural optimization and adoption of intra-procedural techniques. Endoscopic measures are the mainstay of management for post-ERCP bleeding. Escalation to angioembolization or surgery may be required for refractory bleeding. Post-ERCP cholangitis can be reduced with antibiotic prophylaxis in high risk patients. Bile culture-directed therapy plays an important role in antimicrobial treatment.

Pharmacological and Endoscopic Interventions for Prophylaxis of Post-Endoscopic Retrograde Cholangiopancreatography Pancreatitis.

Post-endoscopic retrograde cholangiopancreatography pancreatitis (PEP) represents the most common serious complication after endoscopic retrograde cholangiopancreatography (ERCP). Rectal non-steroidal anti-inflammatory drugs (NSAIDs) and pancreatic duct stenting (PDS) are the prophylactic interventions with more evidence and efficacy; however, PEP still represents a significant source of morbidity, mortality, and economic burden. Chronic statin use has been proposed as a prophylactic method that could be cheap and relatively safe. However, the evidence is conflicting. We aimed to evaluate the impact of endoscopic and pharmacological interventions including chronic statin and aspirin use, on the development of PEP. A retrospective cohort study evaluated consecutive patients undergoing ERCP at John H. Stroger, Jr. Hospital of Cook County in Chicago from January 2015 to March 2018. Univariate and multivariate analyses were performed using logistic regression. A total of 681 ERCPs were included in the study. Twelve (1.76%) developed PEP. Univariate, multivariate, and subgroup analyses did not show any association between chronic statin or aspirin use and PEP. PDS and rectal indomethacin were protective in patients undergoing pancreatic duct injection. Pancreatic duct injection, female sex, and younger age were associated with a higher risk. History of papillotomy was associated with lower risk only in the univariate analysis (all P values < 0.05). Chronic use of statins and aspirin appears to add no additional benefit to prevent ERCP pancreatitis. Rectal NSAIDs, and PDS after appropriate patient selection continue to be the main prophylactic measures. The lower incidence at our center compared with the reported data can be explained by the high rates of rectal indomethacin and PDS, the use of noninvasive diagnostic modalities for patient selection, and the expertise of the endoscopists.

Universal prophylactic rectal nonsteroidal anti-inflammatory drugs with a policy of selective pancreatic duct stenting significantly reduce post-endoscopic retrograde cholangiopancreatography pancreatitis.

Although rectal nonsteroidal anti-inflammatory drugs (NSAIDs) have been shown to be effective for the prevention of post-ERCP (endoscopic retrograde cholangiopancreatography) pancreatitis (PEP) in high-risk patients, the benefit in average-risk patients is unclear. We aimed at assessing the benefit of prophylactic rectal NSAIDs in unselected consecutive patients to prevent PEP. All patients undergoing index ERCP procedures from January 2018 until March 2020 were included. All patients received prophylactic rectal diclofenac. A prophylactic pancreatic duct (PD) stent was placed if there was repeated PD cannulation, at the discretion of the endoscopist. The frequency of PEP was compared with historical controls. Of 769 patients who underwent ERCP, 34 (4.4%) developed PEP (mild in 29 [85.3%], moderate in four [11.8%] and severe in one [2.9%]). Female gender, precut sphincterotomy, inadvertent PD cannulation and procedural time of > 30minutes predicted PEP in univariate analysis. Inadvertent PD cannulation (OR 4.6, 95% CI: 1.8-11.7; p < 0.001) and procedural time of > 30minutes (OR 8.5, 95% CI: 3.7-10.1; p < 0.001) were independent risk factors on multivariate analysis. When compared with historical controls, the odds of PEP with prophylactic use of rectal NSAIDs and selective PD stenting was 0.54 (CI: 0.31-0.93, p = 0.027). The number needed to treat (NNT) was 22 to prevent one PEP with prophylactic rectal NSAIDs. Routine use of prophylactic rectal NSAIDs effectively prevents the occurrence of PEP in unselected consecutive patients in a real-world scenario.

The safety and efficacy of Ringer's solution loading with rectal diclofenac for prevention of post-endoscopic retrograde cholangiopancreatography pancreatitis: The RESOLUTION-PEP study.

We evaluated the safety and efficacy of aggressive hydration with rectal non-steroidal anti-inflammatory drugs for the prevention of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP). This prospective, single-arm, multicenter trial was conducted at 12 institutions between October 2020 and August 2021. We enrolled 231 patients who had intact papillae and were scheduled to undergo ERCP. All patients were administered rectal diclofenac before ERCP. They received aggressive hydration with intravenous lactated Ringer's solution in an initial bolus of 5 ml/kg at the start of ERCP, followed by 3 ml/kg/h for 8 h after the procedure. The primary outcome was the occurrence of PEP. Secondary outcomes included PEP severity, hyperamylasemia, and adverse events. The mean age of the patients was 68.8±13.7 years, and 81 patients (35.1%) were 75 years or older. Thirteen patients developed PEP (5.6%, 95% confidence interval 3.0%-9.4%). There were 11 cases (4.8%) of mild pancreatitis and two cases (0.9%) of severe pancreatitis. Forty-five patients (19.5%) developed hyperamylasemia and one patient developed non-severe peripheral edema. Aggressive hydration combined with rectal diclofenac may be a promising strategy for the prevention of PEP. Furthermore, it is safe even for older individuals.

Prevention of post-ERCP pancreatitis: current strategies and novel perspectives.

Endoscopic retrograde cholangiopancreatography (ERCP) is an advanced endoscopic procedure that might lead to severe adverse events. Post-ERCP pancreatitis (PEP) is the most common post-procedural complication, which is related to significant mortality and increasing healthcare costs. Up to now, the prevalent approach to prevent PEP consisted of employing pharmacological and technical expedients that have been shown to improve post-ERCP outcomes, such as the administration of rectal nonsteroidal anti-inflammatory drugs, aggressive intravenous hydration, and the placement of a pancreatic stent. However, it has been reported that PEP originates from a more complex interaction of procedural and patient-related factors. Appropriate ERCP training has a pivotal role in PEP prevention strategy, and it is not a chance that a low PEP rate is universally considered one of the most relevant indicators of proficiency in ERCP. Scant data on the acquisition of skills during the ERCP training are currently available, although some efforts have been recently done to shorten the learning curve by way of simulation-based training and demonstrate competency by meeting technical requirements as well as adopting skill evaluation scales. Besides, the identification of adequate indications for ERCP and accurate pre-procedural risk stratification of patients might help to reduce PEP occurrence regardless of the endoscopist's technical abilities, and generally preserve safety in ERCP. This review aims at delineating current preventive strategies and highlighting novel perspectives for a safer ERCP focusing on the prevention of PEP.

Combinatorial Effect of Prophylactic Interventions for Post-ERCP Pancreatitis among Patients with Risk Factors: A Network Meta-Analysis.

The combinatorial effects of prophylactic methods for postendoscopic retrograde cholangiopancreatography pancreatitis (PEP) in patients with risk factors remain unclear. In this network meta-analysis, we compared the efficacy of various prophylactic strategies to decrease the risk of PEP among patients with risk factors. A systematic review was performed to identify randomized controlled trials from PubMed, Embase, and the Cochrane Library through July 2021. We used frequentist network meta-analysis to compare the rates of PEP among patients who received prophylactic treatments as follows: class A, rectal nonsteroidal anti-inflammatory drugs; class B, prophylactic pancreatic stent; class C, aggressive hydration; or control, no prophylaxis or active control. We selected those studies that included patients with risk factors for PEP. We identified 19 trials, comprising 4,328 participants. Class ABC (odds ratio [OR], 0.08; 95% confidence interval [CI], 0.03 to 0.24), class AC (OR, 0.10; 95% CI, 0.02 to 0.47), class AB (OR, 0.12; 95% CI, 0.05 to 0.26), class BC (OR, 0.13; 95% CI, 0.04 to 0.41), class A (OR, 0.16; 95% CI, 0.05 to 0.50), and class B (OR, 0.26; 95% CI, 0.14 to 0.46), were associated with a reduced risk of PEP as compared to that of the control. The most effective prophylaxis was ABC (0.87), followed by AC (0.68), AB (0.65), BC (0.56), A (0.49), and B (0.24) according to P-score. The results of this network meta-analysis suggest that the more prophylactic methods are employed, the better the outcomes. It appears that for patients with risk factors, we need to prevent PEP through the use of these well proven combination strategies.

Rectal administration of low-dose diclofenac does not reduce post-endoscopic retrograde cholangiopancreatography pancreatitis: a propensity score matching analysis.

Endoscopic retrograde cholangiopancreatography (ERCP) is a popular technique; however, post-ERCP pancreatitis (PEP) remains a major adverse event. The administration of rectal nonsteroidal anti-inflammatory drugs (NSAIDs) is reportedly effective in preventing PEP. However, the recommended dose varies and the efficacy of low-dose rectal NSAIDs remains unclear. Therefore, we decided to investigate the effectiveness of low-dose rectal diclofenac on PEP prevention, using propensity score matching. This single-center retrospective study included 401 patients who underwent ERCP between July 2015 and March 2020. After December 2016, we administered rectal diclofenac within 30min before the ERCP procedure as widely as possible. Patients were divided into those who did (diclofenac group) and did not (control group) receive rectal diclofenac. Patients weighing ≥ 50kg were administered a 50mg dose, while those weighing < 50kg were administered a 25mg dose. The incidence and severity of PEP in the two groups were assessed by propensity score matching analysis. Among 401 patients undergoing ERCP, 367 fulfilled the inclusion criteria. Overall, 187 patients received rectal diclofenac (diclofenac group) and 180 did not (control group). After propensity score matching, 105 pairs were selected for evaluation. Overall, seven (6.7%) patients in the diclofenac group and 10 (9.5%) in the control group developed PEP (P = 0.45). Moderate or severe PEP occurred in four (3.8%) patients in the diclofenac group and six (5.7%) in the control group (P = 0.52). The administration of low-dose rectal diclofenac could not reduce the incidence and severity of PEP.

Efficacy of pancreatic duct stenting to prevent postendoscopic retrograde cholangiopancreatography pancreatitis after covered self-expandable metal stentdeployment.

Although covered self-expandable metal stents (CSEMSs) are associated with the risk of postendoscopic retrograde cholangiopancreatography (ERCP) pancreatitis due to pancreatic duct (PD) orifice obstruction, they are often used for biliary drainage treatment in malignant biliary obstruction (MBO). This study aimed to investigate the efficacy of PD stenting in preventing post-ERCP pancreatitis after CSEMS implantation. This retrospective cohort study analyzed 554 patients with transpapillary CSEMS for MBO. Patients with noninitial deployment, benign disease, CSEMS deployment above the papilla, surgically altered anatomy, uncovered self-expandable metal stents, multiple thin self-expandable metal stents, and unavailable procedure videos were excluded. Logistic regression analysis estimated the association between PD stenting and post-ERCP pancreatitis incidence. We adjusted for age, sex, pancreatitis history, prophylactic rectal nonsteroidal anti-inflammatory drug use, naïve papilla, MBO etiology, and prolonged biliary cannulation time. Among 554 patients, 67 (12.1%) experienced post-ERCP pancreatitis. Post-ERCP pancreatitis was recorded in 13.7% of patients in the non-PD stenting and 4.3% in the PD stenting groups. Pancreatic duct stenting was associated with lower risks of post-ERCP pancreatitis (odds ratio [OR] 0.28; 95% confidence interval [CI] 0.099-0.79; P = 0.028). In multivariable analysis, the association between PD stenting and lower post-ERCP pancreatitis incidence was consistent (OR 0.19; 95% CI 0.062-0.58; P = 0.0034). Pancreatic duct stenting could reduce the risk of post-ERCP pancreatitis after CSEMSs.

Rectal nonsteroidal anti-inflammatory drugs, glyceryl trinitrate, or combinations for prophylaxis of post-endoscopic retrograde cholangiopancreatography pancreatitis: A network meta-analysis.

BACKGROUNDAcute pancreatitis is the most common and severe complication of endoscopic retrograde cholangiopancreatography (ERCP). Recent evidence suggests that combinations based on rectal nonsteroidal anti-inflammatory drugs (NSAIDs) are more beneficial in preventing post-ERCP pancreatitis (PEP). Randomized controlled trials (RCTs) have also demonstrated the efficacy of glyceryl trinitrate (GTN). We conducted a network meta-analysis to compare NSAIDs and GTN for prevention of PEP and to determine whether they are better in combination.AIMTo compare NSAIDs and GTN for prevention of PEP and to determine whether they are better in combination.METHODSA systematic search was done for full-text RCTs of PEP in PubMed, Embase, Science Citation Index, and the Cochrane Controlled Trials database. Inclusion and exclusion criteria were used to screen for eligible RCTs. The major data were extracted by two independent reviewers. The frequentist model was used to conduct this network meta-analysis and obtain the pairwise OR and 95%CI. The data were then extracted and assessed on the basis of the Reference Citation Analysis (https://www.referencecitationanalysis.com/).RESULTSTwenty-four eligible RCTs were selected, evaluating seven preventive strategies in 9416 patients. Rectal indomethacin 100 mg plus sublingual GTN (OR: 0.21, 95%CI: 0.09–0.50), rectal diclofenac 100 mg (0.34, 0.18–0.65), sublingual GTN (0.34, 0.12–0.97), and rectal indomethacin 100 mg (0.49, 0.33–0.73) were all more efficacious than placebo in preventing PEP. The combination of rectal indomethacin and sublingual GTN had the highest surface under the cumulative ranking curves (SUCRA) probability of (92.2%) and was the best preventive strategy for moderate-to-severe PEP with a SUCRA probability of (89.2%). CONCLUSIONCombination of rectal indomethacin 100 mg with sublingual GTN offered better prevention of PEP than when used alone and could alleviate the severity of PEP.

Prophylaxis of Post-Endoscopic Retrograde Cholangiopancreatography Pancreatitis Using Temporary Pancreatic Stents Versus Rectal Nonsteroidal Anti-inflammatory Drugs: A Randomized Controlled Trial.

Both pancreatic stenting and rectal nonsteroidal anti-inflammatory drugs (NSAIDs) prevent post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis. The aim of the study was to compare post-ERCP pancreatitis (PEP) prophylaxis using pancreatic stents and/or rectal NSAIDs prospectively. A total of 321 patients undergoing ERCP were studied. Each patient was randomly allocated to receive pancreatic stent placement (PS), 50 mg of rectal diclofenac (NSAID), or both (PS + NSAID) for PEP prophylaxis. The primary outcome was the occurrence rate of PEP, and secondary outcomes included the severity of PEP and serum pancreatic amylase and lipase levels on the day after ERCP. Five patients (PS: 2/101, NSAID: 1/106, PS + NSAID: 2/102) developed PEP, and the overall occurrence rate of PEP was 1.6% (5/309). The occurrence rates of PEP in the PS, NSAID, and PS + NSAID groups were statistically equivalent with an equivalent margin of 10%. The severity of PEP was mild in all 5 patients. Median serum pancreatic amylase and lipase levels in the NSAID group were significantly lower than those in the PS and PS + NSAID groups. Rectal administration of 50 mg of diclofenac may become a first-line therapy for PEP prophylaxis in our country.

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.

Optimal timing of rectal diclofenac in preventing post-endoscopic retrograde cholangiopancreatography pancreatitis.

Background and study aims Rectal nonsteroidal anti-inflammatory drug (NSAID) prophylaxis reduces incidence of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis. Direct comparisons to the optimal timing of administration, before or after ERCP, are lacking. Therefore, we aimed to assess whether timing of rectal NSAID prophylaxis affects the incidence of post-ERCP pancreatitis. Patients and methods We conducted an analysis of prospectively collected data from a randomized clinical trial. We included patients with a moderate to high risk of developing post-ERCP pancreatitis, all of whom received rectal diclofenac monotherapy 100-mg prophylaxis. Administration was within 30 minutes before or after the ERCP at the discretion of the endoscopist. The primary endpoint was post-ERCP pancreatitis. Secondary endpoints included severity of pancreatitis, length of hospitalization, and Intensive Care Unit (ICU) admittance. Results We included 346 patients who received the rectal NSAID before ERCP and 63 patients who received it after ERCP. No differences in baseline characteristics were observed. Post-ERCP pancreatitis incidence was lower in the group that received pre-procedure rectal NSAIDs (8 %), compared to post-procedure (18 %) (relative risk: 2.32; 95% confidence interval: 1.21 to 4.46, P = 0.02). Hospital stays were significantly longer with post-procedure prophylaxis (1 day; interquartile range [IQR] 1–2 days vs. 1 day; IQR 1–4 days; P = 0.02). Patients from the post-procedure group were more likely to be admitted to the ICU (1 patient [0.3 %] vs. 4 patients [6 %]; P = 0.002). Conclusions Pre-procedure administration of rectal diclofenac is associated with a significant reduction in post-ERCP pancreatitis incidence compared to post-procedure use.

Rectal NSAIDs-based combination modalities are superior to single modalities for prevention of post-endoscopic retrograde cholangiopancreatography pancreatitis: a network meta-analysis.

Background/AimsDifferent modalities have been employed to reduce the risk and severity of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP). However, there has been a paucity of studies comparing the efficacy of various prophylactic modalities for preventing PEP. This network meta-analysis (NMA) aimed to determine the relative efficacy of pancreatic duct stents and pharmacological modalities for preventing PEP.MethodsWe performed a systematic and comprehensive search to identify and analyze all randomized controlled studies published until June 2020 that examined the effectiveness of pancreatic duct stents, rectal non-steroidal anti-inflammatory drugs (NSAIDs) based regimens, hydration, and their combinations for the prevention of PEP. The primary outcome was the frequency of PEP. An NMA was performed to combine direct and indirect comparisons of different prophylactic modalities.ResultsThe NMA included 46 studies evaluating 18 regimens in 16,241 patients. Based on integral analysis of predictive interval plots, and expected mean ranking and surface under the cumulative ranking curve values, combination prophylaxis with indomethacin + lactated Ringer’s solution (LR), followed by diclofenac + nitrate and indomethacin + normal saline, was found to be the most efficacious modality for the overall prevention of PEP. Indomethacin + LR, followed by diclofenac and pancreatic duct stents, was the most efficacious modality for high-risk groups.ConclusionsRectal NSAIDs-based combination regimens with aggressive hydration or nitrate are superior to single modalities for the prevention of PEP.

Non-steroidal anti-inflammatory drugs, intravenous fluids, pancreatic stents, or their combinations for the prevention of post-endoscopic retrograde cholangiopancreatography pancreatitis: a systematic review and network meta-analysis

Non-steroidal anti-inflammatory drugs (NSAIDs), intravenous fluid, pancreatic stents, or combinations of these have been evaluated in randomised controlled trials (RCTs) for the prevention of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis, but the comparative efficacy of these treatments remains unclear. Our aim was to do an exploratory network meta-analysis of previous RCTs to systematically compare the direct and indirect evidence and rank NSAIDs, intravenous fluids, pancreatic stents, or combinations of these to determine the most efficacious method of prophylaxis for post-ERCP pancreatitis. We searched PubMed, Embase, and the Cochrane Central Register from inception to Nov 15, 2020, for full-text RCTs that evaluated the efficacy of NSAIDs, pancreatic stents, intravenous fluids, or combinations of these for post-ERCP pancreatitis prevention in adult (aged ≥18 years) patients undergoing ERCP. Summary data from intention-to-treat analyses were extracted from published reports. We analysed incidence of post-ERCP pancreatitis across studies using network meta-analysis under the frequentist framework, obtaining pairwise odds ratios (ORs) and 95% CIs. We used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system for the confidence rating. This study is registered with PROSPERO, CRD42020172606. We identified 1503 studies, of which 55 RCTs evaluating 20 interventions in 17 062 patients were included in the network meta-analysis. The mean incidence of post-ERCP pancreatitis in the placebo or active control group was 12·2% (95% CI 11·4-13·0). Normal saline plus rectal indometacin (OR 0·02, 95% CI 0·00-0·40), intramuscular diclofenac 75 mg (0·24, 0·09-0·69), intravenous high-volume Ringer's lactate plus rectal diclofenac 100 mg (0·30, 0·16-0·55), intravenous high-volume Ringer's lactate (0·31, 0·12-0·78), 5-7 Fr pancreatic stents (0·35, 0·26-0·48), rectal diclofenac 100 mg (0·36, 0·25-0·52), 3 Fr pancreatic stents (0·47, 0·26-0·87), and rectal indometacin 100 mg (0·60, 0·50-0·73) were all more efficacious than placebo for preventing post-ERCP pancreatitis in pairwise comparisons. 5-7 Fr pancreatic stents (0·59, 0·41-0·84), intravenous high-volume Ringer's lactate plus rectal diclofenac 100 mg (0·49, 0·26-0·94), intravenous standard-volume normal saline plus rectal indometacin 100 mg (0·04, 0·00-0·66), and rectal diclofenac 100 mg (0·59, 0·40-0·89) were more efficacious than rectal indometacin 100 mg. The GRADE confidence rating was low to moderate for 98·3% of the pairwise comparisons. This systematic review and network meta-analysis summarises the available literature on NSAIDs, pancreatic stents, intravenous fluids, or combinations of these for prophylaxis of post-ERCP pancreatitis. Rectal diclofenac 100 mg is the best performing rectal NSAID in this network meta-analysis. Combinations of prophylaxis might be more effective, but there is little evidence. These findings help to establish prophylaxis of post-ERCP pancreatitis for future research and practice, and could reduce costs and increase adoption of prophylaxis. None.

Efficacy of Per Rectal Non-Steroidal Anti-inflammatory Drugs to Prevent Post Endoscopic Retrograde Cholangiopancrea-tography Pancreatitis: A Comparative Study

Background and aims: Acute pancreatitis is the most common major post-ERCP complication ranging as high as 10% to 40%. Rectal NSAIDS (Indomethacin or Diclofenac) seem to be the most promising drugs to prevent post ERCP pancreatitis. We performed a trial to investigate the efficacy of indomethacin or diclofenac.&#x0D; Methods: A prospective randomized comparative trial was performed at Dhaka from January 2013 to June 2019. Patients undergoing ERCP were randomly selected to group-A and group-B. Diclofenac 50mg suppository was given to group-A patients and Indomethacin 100mg suppository was given to group-B patients during or just after ERCP. The primary outcome was acute pancreatitis following the procedure which was defined by new upper abdominal pain, elevation of pancreatic lipase to at least 3 times the upper limit of normal level 24 hours after ERCP and hospitalization for 02 nights. Retrospective analysis of data of 122 patients who had undergone ERCP in 2012 but had no history of rectal NSAIDS (group C) was done.&#x0D; Results: Total 613 patients were included in this study and followed up. Post ERCP pancreatitis developed in 21(8.5%) patients of group-A (n=247), in 19(7.78%) patients of group-B (n=244) and in 20(17.85%) patients of group-C (n=122)(p=0.02). Moderate to severe pancreatitis was found in 08(3.23%) patients of group-A, in 06(2.45%) patients of group-B and in 12(9.83%) patients of group-C(p= 0.01). Administration of these NSAIDS showed clear benefit to reduce occurrence of Post ERCP pancreatitis when compared with no drug group (P=0.01). The efficacy of indomethacin compared with diclofenac was similar (P=0.874).&#x0D; Conclusions: Prophylactic use of rectal indomethacin or diclofenac during or just after ERCP significantly reduces the incidence of post ERCP pancreatitis. These NSAIDs are inexpensive, safe and should be used routinely in each patient undergoing ERCP.&#x0D; Bangladesh J Medicine July 2021; 32(2) : 99-106

Network meta-analysis of prophylactic pancreatic stents and non-steroidal anti-inflammatory drugs in the prevention of moderate-to-severe post-ERCP pancreatitis

BackgroundThere is an ongoing debate that non-steroidal anti-inflammatory drugs (NSAID) or prophylactic pancreatic stents (PPS) are more beneficial in preventing post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP). In our present network meta-analysis, we aimed to compare PPSs to rectal NSAIDs in the prevention of moderate and severe PEP in average- and high-risk patients. MethodsWe performed a systematic search for randomized controlled trials (RCT) from MEDLINE (via PubMed), Embase and Cochrane Central databases. RCTs using prophylactic rectal NSAIDs or PPSs in patients subjected to ERCP at average- and high-risk population were included. The main outcome was moderate and severe PEP defined by the Cotton criteria. Pairwise Bayesian network meta-analysis was performed, and interventions were ranked based on surface under cumulative ranking (SUCRA) values. ResultsSeven NSAID RCTs (2593 patients), and 2 PPS RCTs (265 patients) in the average-risk, while 5 NSAID RCTs (1703 patients), and 8 PPS RCTs (974 patients) in the high-risk group were included in the final analysis. Compared to placebo, only PPS placement reduced the risk of moderate and severe PEP in both patient groups (average-risk: RR = 0.07, 95% CI [0.002–0.58], high-risk: RR = 0.20, 95% CI [0.051–0.56]) significantly. Rectal NSAID also reduced the risk, but this effect was not significant (average-risk: RR = 0.58, 95% CI [0.22–1.3], high-risk: RR = 0.58, 95% CI [0.18–2.3]). Based on SUCRA, PPS placement was ranked as the best preventive method. ConclusionProphylactic pancreatic stent placement but not rectal NSAID seems to prevent moderate-to-severe PEP better both, in average- and high-risk patients.