Rectal Administration Of Indomethacin Research Articles

Indomethacin Does Not Reduce Post-ERCP Pancreatitis in High-Risk Patients Receiving Pancreatic Stenting.

Rectal indomethacin reduces pancreatitis following endoscopic retrograde cholangiopancreatography (ERCP). However, there is insufficient evidence regarding its added benefits in patients already receiving prophylactic pancreatic stenting. Our goal was to evaluate the impact of indomethacin in high-risk patients undergoing pancreatic stenting. A cohort study was conducted on all patients who underwent the rescue cannulation technique for challenging bile duct cannulation (selected high-risk patients). Patients were split into two groups based on the prophylaxis method for post-ERCP pancreatitis (PEP): one receiving a combination of indomethacin and pancreatic stenting, while the other received pancreatic stenting alone. Comparative analyses were carried out on PEP, hyperamylasemia, gastrointestinal bleeding, and postoperative hospital stay among post-ERCP pancreatitis patients. Between November 2017 and May 2023, a total of 607 patients with native papillae were enrolled, with 140 grouped into the indomethacin plus stent group and 467 into the stent alone group. The overall PEP rate was 4.4% in the entire cohort, with no statistical differences observed between the groups in terms of PEP rates (P = 0.407), mild PEP (P = 0.340), moderate to severe PEP (P = 1.000), hyperamylasemia (P = 0.543), gastrointestinal bleeding (P = 0.392), and postoperative hospital stay (P = 0.521). Furthermore, sensitivity analysis using multivariable analysis also validated these findings. Indomethacin did not reduce the incidence or severity of PEP in high-risk patients who routinely received prophylactic pancreatic stent placement. Therefore, the additional administration of rectal indomethacin to further mitigate PEP appears to be not necessary.

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.

Patient-related post-ERCP pancreatitis (PEP) risk factors between two groups of patients: Prophylactic pancreatic stent and rectal indomethacin.

Pancreatitis is one of the most crucial complications following endoscopic retrograde cholangiopancreatography (ERCP). The purpose of the current study was to investigate patient-related post-ERCP pancreatitis (PEP) risk factors in two groups of patients: prophylactic pancreatic stent and rectal indomethacin. Two different prophylactic modalities were planned and complications were assessed based on the defined inclusion criteria. In this study, the patients were evaluated for the procedure and patient-related risk factors in post-ERCP pancreatitis in the recipient groups of the prophylactic pancreatic stent and rectal indomethacin. Pancreatitis was confirmed in 27 of all 170 selected patients after ERCP. By univariate analysis, two variables were significant with the development of PEP. Regarding the patient-related risk factors, unique subjects with common bile duct (CBD) dilated 10mm were more exposed to an increased chance of PEP (P=0. 015); meanwhile, other factors did not correlate with the increased possibility of PEP in both groups. The only procedure-related risk factor for PEP was the deep cannulation of the pancreatic duct in both groups during the procedure with an incremental significant incidence of pancreatitis (P=0.005). Comparison of prophylactic pancreatic stent and rectal indomethacin showed no effects in term of post ERCP pancreatitis reduction. Additionally, there was no significant difference between these two strategies in the rate of PEP. Prophylactic pancreatic duct stents and administration of rectal indomethacin cannot have particular approaches for reducing the possible occurrence of PEP. The increase in time of deep cannulation and the presence of CBD dilation <10mm could be considered as important risk factors.

Possibilities of microemulsion application in rectal administration of indomethacin

Abstract Rectal administration is a suitable route of administration for drugs that are either very irritating to the intestine (e.g., indomethacin) or are more effective when the first-pass effect in the liver is circumvented. Microemulsions are a tool for the improvement of penetration of sparingly soluble drugs. They are mainly used in topical and transdermal drug delivery. However, they find application also in other routes of administration, mainly due to their ability to solubilize sparingly soluble drugs. The selection of a suppository base depends on the physical properties of the drug. The study focused on evaluating the effect of the microemulsion as the solubilizer of sparingly soluble indomethacin in hydrophilic and lipophilic suppository bases compared with Polysorbate 80 as the excipient contained in the microemulsion. The reference suppositories were prepared by the traditional moulding technique from Adeps solidus or Macrogol suppository base without the previous drug solubilization. The microemulsion-based suppositories were prepared after the initial solubilization of the drug in the microemulsion or Polysorbate 80, followed by the addition of suppository base to maintain the same drug/solubilizer ratio. The suppositories were tested for softening time, hardness, and uniformity of mass. The dissolution test was performed using the dialysis tubing method in the basket apparatus. The amount of indomethacin released into the dissolution medium was determined spectrophotometrically at 320 nm. The results indicate that solubilization of indomethacin in the microemulsion had a positive effect on in vitro drug release but not as significant as in the case of Polysorbate 80 used alone. The enhancement ratio for Polysorbate 80 in Adeps suppositories was 2.9, for the microemulsion in Adeps suppositories was 1.1, and for Polysorbate 80 in Macrogol suppositories was 7.4 after 3 hours. The test of uniformity of mass had shown that all suppositories (reference, solubilizer-containing) are within the permitted limits. The softening time was reduced by adding the solubilizer to each type of suppository base.

Comparison of stent and indomethacin suppository efficacy in the prevention of acute pancreatitis after ERCP.

Objective:We aimed to compare stent and indomethacin suppository efficacy in the prevention of acute pancreatitis after ERCP.Materials and Methods:76 high-risk patients undergoing ERCP were included in the study. The patients were divided into three groups as indomethacin group, stent group and control group. Indomethacin group (n = 32) received 100 mg rectal indomethacin immediately after ERCP. A 5F pancreatic stent was applied to the stent group (n = 16) during ERCP. No prophylaxis was given to the control group (n = 28).Results:There was no difference between the groups in terms of age and gender. ERCP pancreatitis was seen in 9.2% (7/76) of the patients. The incidence of ERCP-induced pancreatitis (PEP) was 3.1% (1/32) in the indomethacin group and 21.4% (6/28) in the control group. PEP was not seen in the stent group (0/16). The incidence of PEP was significantly lower in the indomethacin group than in the control group (p = 0.043). However, no significant difference was found between the stent and control groups, stent and indomethacin groups in terms of PEP frequency (p = 0.072, p: 0.90 respectively).Conclusion:According to the results of our study, rectal indomethacin administration decreased the frequency of PEP in high-risk patients. However, there was no significant difference in PEP prophylaxis between the stent and indomethacin groups.

Evaluation of Preoperative Administration of Rectal Indomethacin in Reducing the Severity of Ileus after Open Cholecystectomy

Introduction: Ileus or transient intestinal motility disorder is one of the problems after surgery, which poses challenges facing the medical team. Previous studies approved the preemptive effects of non-steroidal anti-inflammatory drugs (NSAIDs) on ileus; however, the majority of them have focused on animal models. This study aimed to investigate the effects of administration of rectal indomethacin in reducing ileus in patients who underwent cholecystectomy. Materials and Methods: This randomized controlled trial included 40 patients with cholelithiasis who were divided into two groups of indomethacin (n=20) and placebo (n=20). The indomethacin group received 100 mg rectal indomethacin before the operation. Cholecystectomy was performed using an open technique. The recovery of bowel functions (i.e. the time of the first flatus passage, return of appetite, and total dosage of opioid analgesic medications) was evaluated in this study. Results: Time of the first ileus passage (P=0.004), return of appetite time (P=0.06), and reduction of opioid usage (65.62±5.5 mg/day versus 93.26±2.56) were significantly shorter in the indomethacin group, compared to the placebo group. Furthermore, none of the patients had any significant indomethacin-related complications. Conclusion: According to the outcomes of this study, it is concluded that preoperative administration of NSAIDS can be helpful in postoperative ileus reduction.

Is Needle Knife Fistulotomy a Shortcut to Preventing Postendoscopic Retrograde Pancreatitis?

Post-endoscopic retrograde cholangiopancreatography pancreatitis (PEP) remains a common and potentially severe adverse event, with continued research efforts to reduce PEP incidence. Robust evidence exists supporting the selective use of pancreatic duct stent placement, administration of rectal indomethacin, wire-guided cannulation technique, and aggressive fluid hydration using lactated Ringer solution. Jang et al. presented a randomized control trial describing primary needle-knife fistulotomy and its benefit for biliary access and reduced PEP incidence. Although these data are compelling, we discuss the key study limitations and the need for further studying the role of primary needle-knife fistulotomy.

Tacrolimus and Indomethacin Are Safe and Effective at Reducing Pancreatitis After Endoscopic Retrograde Cholangiopancreatography in Patients Who Have Undergone Liver Transplantation

Biliary complications occur in up to 25% of patient following liver transplantation and are often managed by endoscopic retrograde cholangiopancreatography (ERCP). Pancreatitis is the most common adverse event after ERCP (PEP). Tacrolimus and rectal indomethacin have each been reported to reduce risk of PEP. We investigated the incidence of PEP in patients who have undergone ERCP after liver transplantation and the effectiveness of tacrolimus and/or indomethacin in reducing risk of PEP. We performed a retrospective study of 337 patients who underwent ERCP (n = 937 procedures) for biliary complications after liver transplantation from June 1, 2007 through December 1, 2015. After June 1, 2012, rectal indomethacin (100 mg) was routinely administered at the conclusion of the ERCP unless patients had contraindications. Indomethacin was given after 286 ERCP procedures. After excluding patients with acute/chronic rejection, 323 patients were maintained on a stable dose of tacrolimus prior to ERCP (901 procedures). We collected data on demographic and clinical variables, pre-procedural tacrolimus trough levels, and development of PEP. We calculated adjusted odds ratios (ORs) for the association between tacrolimus and indomethacin use and risk of PEP using mixed-effects multivariable logistic regression. The primary outcome was development of PEP; secondary outcomes included the development moderate-to-severe PEP, cholangitis and bleeding. PEP occurred after 2.2% of ERCP procedures. A trough level of tacrolimus above 2.5 ng/mL was associated with 79% lower odds of PEP (OR, 0.21; 95% CI, 0.06-0.72; P = .01). Indomethacin was associated with a 91% reduction in risk of PEP (OR, 0.09; 95% CI, 0.01-0.85; P = .03). Indomethacin use did not affect rates of bleeding or cholangitis or decrease in glomerular filtration rate. In patients with trough levels of tacrolimus above 2.5 ng/mL, addition of indomethacin reduced the odds of PEP by 93% compared with patients who were unexposed to indomethacin. (OR, 0.07; 95% CI, 0.01-0.90; P = .04). In a retrospective study of patients who underwent ERCP for biliary complications after liver transplantation, we found trough levels of tacrolimus above 2.5 ng/mL to significantly reduce risk for PEP. Rectal administration of indomethacin after ERCP significantly decreased rates of pancreatitis, and reduced risk further in patients given tacrolimus. Administration of both drugs prevented patients from developing moderate or severe pancreatitis. Indomethacin did not worsen renal function in patients with chronic kidney disease.

Post-endoscopic retrograde cholangiopancreatography pancreatitis: A systematic review for prevention and treatment.

BACKGROUNDPost endoscopic retrograde cholangiopancreatography (ERCP) is comparatively complex application. Researchers has been investigated prevention of post-ERCP pancreatitis (PEP), since it has been considered to be the most common complication of ERCP. Although ERCP can lead various complications, it can also be avoided.AIMSTo study the published evidence and systematically review the literature on the prevention and treatment for PEP.METHODSA systematic literature review on the prevention of PEP was conducted using the electronic databases of ISI Web of Science, PubMed and Cochrane Library for relevant articles. The electronic search for the review was performed by using the search terms “Post endoscopic retrograde cholangiopancreatography pancreatitis” AND “prevention” through different criteria. The search was restricted to randomized controlled trials (RCTs) performed between January 2009 and February 2019. Duplicate studies were detected by using EndNote and deleted by the author. PRISMA checklist and flow diagram were adopted for evaluation and reporting. The reference lists of the selected papers were also scanned to find other relevant studies.RESULTS726 studies meeting the search criteria and 4 relevant articles found in the edited books about ERCP were identified. Duplicates and irrelevant studies were excluded by screening titles and abstracts and assessing full texts. 54 studies were evaluated for full text review. Prevention methods were categorized into three groups as (1) assessment of patient related factors; (2) pharmacoprevention; and (3) procedural techniques for prevention. Most of studies in the literature showed that young age, female gender, absence of chronic pancreatitis, suspected Sphincter of Oddi dysfunction, recurrent pancreatitis and history of previous PEP played a crucial role in posing high risks for PEP. 37 studies designed to assess the impact of 24 different pharmacologic agents to reduce the development of PEP delivered through various administration methods were reviewed. Nonsteroidal anti-inflammatory drugs are widely used to reduce risks for PEP. Rectal administration of indomethacin immediately prior to or after ERCP in all patients is recommended by European Society for Gastrointestinal Endoscopy guidelines to prevent the development of PEP. The majority of the studies reviewed revealed that rectally administered indomethacin had efficacy to prevent PEP. Results of the other studies on the other pharmacological interventions had both controversial and promising results. Thirteen studies conducted to evaluate the efficacy of 4 distinct procedural techniques to prevent the development of PEP were reviewed. Pancreatic Stent Placement has been frequently used in this sense and has potent and promising benefits in the prevention of PEP. Studies on the other procedural techniques have had inconsistent results.CONCLUSIONPrevention of PEP involves multifactorial aspects, including assessment of patients with high risk factors for alternative therapeutic and diagnostic techniques, administration of pharmacological agents and procedural techniques with highly precise results in the literature.

Risk of Post-Endoscopic Retrograde Cholangiopancreatography Pancreatitis After Double-Guidewire Biliary Cannulation in an Average-Risk Population.

Double-guidewire cannulation (DGC) for selective biliary access has been associated with increased risk of post-ERCP pancreatitis (PEP) in patients who have had pancreatic duct (PD) contrast injection. The objective of this study was to determine whether DGC increases PEP risk in standard risk individuals when controlling for procedural aspects such as PD contrast injection. Consecutive adults with native papillae who underwent endoscopic retrograde cholangiopancreatography from 2009 to 2014 were retrospectively identified, and clinical data were collected. There were 879 subjects who met inclusion criteria. Increased incidence of PEP was observed after DGC (18% with DGC vs 4% without DGC, P < 0.005). Additional factors associated with increased PEP risk included the following: PD contrast injection, PD wire cannulations, and biliary stent placement. The association between DGC and increased PEP risk remained significant in a multivariate model controlling for age, sex, PD contrast injection, biliary sphincterotomy, biliary stent placement, and rectal indomethacin administration (odds ratio = 2.87, 95% confidence interval = 1.23-6.36). Double-guidewire cannulation is associated with increased risk of PEP when controlling for confounding variables. Prospective studies should be undertaken to assess whether prophylactic interventions reduce risk of PEP after DGC in an average-risk population.

Pre-endoscopic retrograde cholangiopancreatography (ERCP) administration of rectal indomethacin in unselected patients to reduce post-ERCP pancreatitis: A systematic review and meta-analysis.

Previous studies have reported that peri-procedural administration of rectal indomethacin reduces the risk of pancreatitis in patients undergoing endoscopic retrograde cholangiopancreatography (ERCP). Based on these studies, gastrointestinal (GI) societies recommend prophylactic rectal indomethacin for all patients undergoing ERCP. However, recent studies have reported contradictory results. The aim of this study was to perform a systematic review and meta-analysis to estimate the pooled relative risk (RR) of post-ERCP pancreatitis (PEP) in unselected patients who received rectal indomethacin before the ERCP (pre-ERCP) compared to patients who received pre-ERCP rectal placebo. We conducted a comprehensive search of multiple electronic databases and conference proceedings (from inception through September 1, 2017) to identify randomized control trials (RCTs) investigating the role of pre-ERCP rectal indomethacin in reducing the risk of PEP in unselected patients undergoing ERCP. The databases included Ovid, Medline, In-Process, and Other Non-Indexed Citations, Ovid MEDLINE, Ovid EMBASE, Ovid Cochrane Central Register of Controlled Trials, Ovid Cochrane Database of Systematic Reviews, Scopus, and Web of Science. We calculated a pooled estimate of the RR of PEP in patients who received pre-ERCP rectal indomethacin compared to patients who received pre-ERCP rectal placebo. The meta-analysis was performed using the random effects model. Six RCTs with a total of 2229 patients were included in the final meta-analysis. There were 1143 patients in the rectal indomethacin group and 1086 patients in the rectal placebo group. There were 71 events of PEP in the rectal indomethacin group and 114 events of PEP in the rectal placebo group. Pre-ERCP administration of rectal indomethacin significantly reduced the risk of PEP compared to pre-ERCP rectal placebo (RR 0.60, 95% CI, 0.45-0.80; p<0.0001). There was no heterogeneity between the studies (I2= 0). The results of this meta-analysis support the routine pre-ERCP administration of rectal indomethacin in unselected patients to prevent PEP.

Rectal Indomethacin Is Protective against Pancreatitis after Endoscopic Retrograde Cholangiopancreatography: Systematic Review and Meta-Analysis.

Background and Aim Rectal indomethacin was reported to be effective for postendoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) prophylaxis. However, the preventive effect of indomethacin for average-risk patients remains unclear. Recently, some conflicting evidence was addressed by recent articles. We aimed to determine the protective role of indomethacin in PEP based on the latest available literature. Methods A systematic literature search was conducted using PubMed, Embase, Web of Science, and the Cochrane Library to identify related articles published before October 2016. Studies that evaluated the administration of indomethacin in the prevention of PEP were included in the analysis. We adopted a random-effects model to calculate the overall relative risk (RR) and 95% confidence interval (CI). Results Ten trials from an initial search were finally included in the meta-analysis. The administration of rectal indomethacin significantly reduced the incidence of PEP in consecutive ERCP population (RR, 0.63; 95% CI, 0.50–0.77). There was no significant heterogeneity across included studies (I 2 = 14.2%, P = 0.31). Further subgroup analyses also revealed that rectal indomethacin could protect the individuals at high and average risks and reduced severity of PEP. Pre-ERCP administration of indomethacin seemed to be better than the post-ERCP given. There was no evidence of significant publication bias. Conclusions Rectal administration of indomethacin is an effective approach to prevent the incidence of PEP in both high- and average-risk populations undergoing ERCP. However, more high-quality RCTs are needed to further investigate the optimal timing for the administration of indomethacin.

National Trend in Post-Endoscopic Retrograde Cholangiopancreatography (ERCP) Pancreatitis in United States: Analysis of the Nationwide Inpatient Sample (NIS) Database, 2004-2014

Introduction: Post-ERCP pancreatitis (PEP) is the most common complication following ERCP with an estimated annual cost burden in excess of $200 million. In recent years, there have been many advances in preventive strategies, including administration of rectal indomethacin to reduce the incidence of PEP. We report population-based trends over a 10-year period in the incidence of PEP in the United States. Methods: The NIS database was queried to identify patients who had an ERCP with or without PEP from 2004 to 2014. We adopted the previously validated definition for PEP from the NIS database. Appropriate International Classification of Diseases, 9th Revision (ICD-9) diagnosis codes were used to isolate PEP cases. The primary outcome was PEP and secondary outcomes were in-hospital death, length of stay and hospital costs. Poisson regression models were used to derive adjusted incidence risk ratios (IRR) of PEP and outcomes over time. Independent predictors of mortality and extended length of stay were determined by multivariate logistic regression. Results: Of 381,288 discharges (60.8% females) for patients who underwent ERCP, we found a total of 37,712 discharges for PEP (9.9%). Among the all the patients, 198,269 (52.0%) were performed in teaching hospitals. The median age was 60 (IQR 46-75) years. The number of in-patient ERCPs performed was 32,346 in 2004, with a peak of 38,394 in 2011, and decreased to 34,730 in 2014. From 2004 to 2014, the rate of PEP increased by 23.6 % (8.9% to 11.0%, p-trendTable 1 summarizes the results of the multivariable analysis.Table: Table. Multivariable Logistic Regression Analysis of predictors of post-ERCP pancreatitisConclusion: Over the past decade, there has been a considerable increase in the incidence of PEP in the US despite a simultaneous decrease in number of ERCPs performed. This trend is likely to continue in the near future and suggest a need for a better understanding of pathogenesis and preventive strategies for PEPFigure: Proportion of discharges with post-ERCP pancreatitis.Figure: Number of ERCPs performed.Figure: Mortality, length of stay and cost.

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.

Role for Pre-ERCP Administration of Rectal Indomethacin in Unselected Patients to Prevent Post ERCP Pancreatitis: A Systematic Review and Meta-analysis

Introduction: Previous studies have reported that peri-procedural administration of rectal indomethacin reduces the risk of pancreatitis in patients undergoing endoscopic retrograde cholangiopancreatography (ERCP). Based on these studies, the European and Japanese GI societies recommend prophylactic rectal indomethacin for all patients undergoing ERCP. However, recent studies have reported contradictory results. The aim of this study was to perform a systematic review and meta-analysis to estimate the pooled relative risk (RR) of post-ERCP pancreatitis (PEP) in unselected patients who received rectal indomethacin before the ERCP (pre-ERCP) compared to patients who received pre-ERCP rectal placebo. Methods: We conducted a comprehensive search of multiple electronic databases and conference proceedings (from inception through May 1st, 2016) to identify randomized control trials (RCT) investigating the role of pre-ERCP rectal indomethacin in reducing the risk of PEP in unselected patients undergoing ERCP. The databases included Ovid Medline In-Process & Other Non-Indexed Citations, Ovid MEDLINE, Ovid EMBASE, Ovid Cochrane Central Register of Controlled Trials, Ovid Cochrane Database of Systematic Reviews, Scopus, and Web of Science. We calculated a pooled estimate of the relative risk (RR) of PEP in patients who received pre-ERCP rectal indomethacin compared to patients who received pre-ERCP rectal placebo. The meta-analysis was performed using random effects model. Results: Five RCTs with a total of 1934 patients were included in the final meta-analysis. There were 996 patients in rectal indomethacin group and 938 patients in rectal placebo group. There were 58 events of PEP in the rectal indomethacin group and 71 events of PEP in rectal placebo group. Pre-ERCP administration of rectal indomethacin reduced the risk of PEP compared to pre-ERCP rectal placebo but the difference was not statistically significant (RR, 0.74, 95% CI, 0.47-1.16; p=0.19) (Figure 1). The heterogeneity between studies was low (I2=41).Figure 1Conclusion: The results of this meta-analysis do not support the routine pre-ERCP administration of rectal indomethacin in unselected patients to prevent PEP. Previous meta-analyses which supported use of NSAIDs had broad inclusion criteria which allowed them to include different NSAID medications, routes of administration, timing of NSAID administration and selected patients at high risk for PEP.

Prophylaxis of pancreatitis with intravenous ketoprofen in a consecutive population of ERCP patients: a randomized double-blind placebo-controlled trial.

Background Acute pancreatitis is the most common complication after ERCP, occurring in about 4% of the procedures. Only the placement of pancreatic duct prosthesis and the use of nonsteroidal anti-inflammatory drugs (NSAIDs) have shown benefit in the prevention of post-ERCP pancreatitis (PEP). Although the benefit of rectal administration of indomethacin or diclofenac is recommended by some studies and society guidelines especially in a selected group of high-risk patients, there is so far, no standardization of time or route of NSAID administration. The aim of the current study is to investigate the role of an intravenous NSAID administered before the procedure for PEP prevention. Methods In this randomized double-blind clinical trial, all consecutive patients who underwent ERCP were randomized to receive saline infusion with ketoprofen or saline, immediately before the procedure. Results A total of 477 patients were enrolled and completed follow-up. The majority of patients (72.1%) had bile duct stones, and only 1.5% had a clinical suspicion of sphincter of Oddi dysfunction. PEP developed in 5 of 253 (2%) patients in the placebo group and in 5 of 224 (2.2%) patients in the ketoprofen group (p=1.). Conclusions Intravenous administration of ketoprofen immediately prior to ERCP did not result in reduction in PEP in a general population of ERCP patients.

Prophylactic Effect of Rectal Indomethacin Administration, with and without Intravenous Hydration, on Development of Endoscopic Retrograde Cholangiopancreatography Pancreatitis Episodes: A Randomized Clinical Trial.

Acute Post ERCP Pancreatitis (PEP) is the most common major complication of Endoscopic retrograde cholangiopancreatography (ERCP). The aim of the current study was to assess the utility of single dose rectal indomethacin with and without intravenous perfusion of normal saline to prevent acute pancreatitis. In this randomized clinical trial, 406 patients with choledocolithiasis underwent ERCP. Based on computer-generated numbers, the patients were allocated into 4 groups, each group receiving a different intervention prior to the ERCP procedure. The interventions included rectal indomethacin (100mg) in the first group, intravenous (IV) saline perfusion in the second, both rectal indomethacin and IV saline in the third, and the fourth (control) group receiving rectal glycerin. Serum amylase levels were measured and clinical pancreatitis episodes were quantified and classified according to APACHE II prognostic criteria. Statistical inference was performed using the chi-square or Fisher's exact test for qualitative variables, while Student's zxA-test was used for quantitative variables. A diagnosis of mild pancreatitis was present in 38 (9.4%) cases. The numbers of events in the four study groups were 11, 10, 0, and 17, respectively, corresponding to an absolute risk reduction of 5.2% , 6.2%, 16.2% (number needed to prevent one episode of PEP) and a relative risk reduction of 32%, 38% and 100% in the three study groups, respectively. The frequency of PEP was only significant in the third group (P ˂ 0.001). The combination of rectal indomethacin and intravenous normal saline before ERCP significantly prevents post-ERCP pancreatitis.

Sa1183 A Prospective Randomized Clinical Trial on the Timing of Rectal Indomethacin Administration for the Prevention of Post-ERCP Pancreatitis: A Preliminary Report

Sa1183 A Prospective Randomized Clinical Trial on the Timing of Rectal Indomethacin Administration for the Prevention of Post-ERCP Pancreatitis: A Preliminary Report

Rectal indomethacin versus placebo to reduce the incidence of pancreatitis after endoscopic retrograde cholangiopancreatography: results of a controlled clinical trial.

BackgroundAcute pancreatitis is the most common major complication after endoscopic retrograde cholangiopancreatography (ERCP). Many drugs have been evaluated for prophylaxis, including nonsteroidal anti-inflammatory drugs (NSAIDs), which are potent inhibitors of phospholipase A2 and play a role in the pathogenesis of acute pancreatitis. Rectal NSAIDs have been shown in prospective studies to decrease the incidence of this complication, but the indication is not generalized in clinical practice. The aim of this study was to evaluate the efficacy of rectal administration of indomethacin in reducing the incidence of post-ERCP pancreatitis in high-risk patients.MethodsThis was a controlled clinical trial where patients with an elevated risk of developing post-ERCP pancreatitis were assigned to receive 100 mg of rectal indomethacin or a 2.6 g suppository of glycerin immediately after ERCP, without placement of a pancreatic stent. The patients were determined to be at high risk based on validated patient- and procedure-related risk factors. Post-ERCP pancreatitis was defined as the presence of new upper abdominal pain, hyperamylasemia/hyperlipasemia (at least three times the upper limit) 2 hours after the procedure and hospitalization at least 48 hours because of the complication. Pancreatitis severity was defined according to Cotton’s criteria.ResultsOne hundred sixty-six patients were included; 82 in the study group and 84 in the placebo group. Patients had at least one major and/or two minor risk factors for developing post-ERCP pancreatitis. The incidence of the complication was 4.87 % (4/82) in the study group and 20.23 % (17/84) in the placebo group; this difference was significant (P = 0.01). According to Cotton’s criteria, 17 patients (80.9 %) developed mild pancreatitis and 4 (19.1 %) had moderate pancreatitis; 3 of these 4 patients belonged to the placebo group (P = 0.60). Based on these results, an absolute risk reduction of 0.15 (15 %), a relative risk reduction of 0.75 (75 %) and a number needed to treat of 6.5 patients were calculated to prevent an episode of post-ERCP pancreatitis. There was no mortality.ConclusionsRectal indomethacin reduced the incidence of post-ERCP pancreatitis among patients at high risk of developing this complication.Trial registrationNational Clinical Trials NCT02110810. Date April 7, 2014.

Az endoszkópos retrográd cholangiopancreatographiát követő heveny hasnyálmirigy-gyulladás megelőzése

Over 14,000 endoscopic retrograde cholangiopancreatographies are performed in Hungary annually, and approximately 1400 patients are calculated to develop pancreatititis including 10 cases with fatal outcome. This article reviews the recent and relevant literature and presents a practical guide based on the authors' own experience for the prevention of pancreatitis following endoscopic retrograde cholangiopancreatography. The authors emphasize the importance of careful consideration of indications, analysis of risk factors, avoiding unnecessary diagnostic intervention, a decrease of the attempts for cannulation, early precut, implantation of pancreatic stent in high risk patients, administration of rectal indomethacin or diclofenac, and adequate intravenous fluid replacement.