Prevention Of post-ERCP Pancreatitis Research Articles

Benefits of NSAIDs plus Pancreatic Stenting to Prevent Post-ERCP Pancreatitis

Benefits of NSAIDs plus Pancreatic Stenting to Prevent Post-ERCP Pancreatitis

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

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

Rectal administration of tacrolimus protects against post-ERCP pancreatitis in mice

ObjectiveThere is an unmet clinical need for effective, targeted interventions to prevent post-ERCP pancreatitis (PEP). We previously demonstrated that the serine-threonine phosphatase, calcineurin (Cn) is a critical mediator of PEP and that the FDA-approved calcineurin inhibitors, tacrolimus (Tac) or cyclosporine A, prevented PEP. Our recent observations in preclinical PEP models demonstrating that Cn deletion in both pancreatic and hematopoietic compartments is required for maximal pancreas protection, highlighted the need to target both systemic and pancreas-specific Cn signaling. We hypothesized that rectal administration of Tac would effectively mitigate PEP by ensuring systemic and pancreatic bioavailability of Tac. We have tested the efficacy of rectal Tac in a preclinical PEP model and in cerulein-induced experimental pancreatitis. MethodsC57BL/6 mice underwent ductal cannulation with saline infusion to simulate pressure-induced PEP or were given seven, hourly, cerulein injections to induce pancreatitis. To test the efficacy of rectal Tac in pancreatitis prevention, a rectal Tac suppository (1 mg/kg) was administered 10 min prior to cannulation or first cerulein injection. Histological and biochemical indicators of pancreatitis were evaluated post-treatment. Pharmacokinetic parameters of Tac in the blood after rectal delivery compared to intravenous and intragastric administration was evaluated. ResultsRectal Tac was effective in reducing pancreatic injury and inflammation in both PEP and cerulein models. Pharmacokinetic studies revealed that the rectal administration of Tac helped achieve optimal blood levels of Tac over an extended time compared to intravenous or intragastric delivery. ConclusionOur results underscore the effectiveness and clinical utility of rectal Tac for PEP prophylaxis.

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

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

Utilization pattern of prophylactic measures for prevention of post-ERCP pancreatitis: a National Survey Study.

Post-ERCP pancreatitis (PEP) is the most frequent adverse event of ERCP. Various prophylactic measures are endorsed by the American Society for Gastrointestinal Endoscopy and the European Society of Gastrointestinal Endoscopy to both lower the incidence of PEP and to decrease its severity. The extent to which these interventions are practiced throughout the United States is unclear. The aim of this study was to describe the utilization pattern of various PEP measures and determine factors that affect utilization of these measures. A 27-question electronic survey was distributed using a cloud-based program (Qualtrics). The questions assessed ERCP training, practice setting, experience, practice patterns, and perceptions for PEP prophylaxis interventions. Endoscopists with practices based in the United States listed in the American Society for Gastrointestinal Endoscopy member directory received a survey invitation via e-mail. The invitation outlined the study and contained a link with instructions to complete the voluntary survey if they had an active ERCP practice. Data were de-identified for the purposes of analysis. Of survey respondents (N= 319), 46% reported therapeutic endoscopy fellowship training and 37% practiced in teaching programs. Annualized ERCP volume of >100 cases per year were reported by 47%, with pancreatic ERCP comprising≤5% of procedure volume reported by the majority of respondents (61%). The majority of respondents used prophylactic pancreatic stent (PPS), and 54% reported frequent use during high-risk ERCP. The most common indications for PPS were difficult cannulation, to assist biliary access, and multiple pancreatic duct injections. Most respondents reported frequent use of indomethacin (89%). Of physicians who did not use PPS, use of indomethacin was the most common reason (80%). Variables associated with frequent use of PPS were ERCP fellowship training (P≤ .001), practice at a teaching program (P≤ .001),<10 years in practice (P= .005), higher procedure volume (P≤ .001), and higher proportion of pancreatic cases (P≤ .001). Physicians with higher annual ERCP volume, who teach at hospital-based ERCP practices, and who regularly perform pancreatic ERCP are more likely to use PPS. Therapeutic ERCP fellowship training and recent entry into practice were also associated with PPS utilization. Indomethacin use seems to be more frequent than PPS. Our findings suggest that indomethacin is supplanting PPS as the preferred method of PEP prophylaxis.

An Open-Label Randomized Controlled Trial Comparing Effectiveness of Aggressive Hydration Versus High-dose Rectal Indomethacin in the Prevention of Postendoscopic Retrograde Cholangiopancreatographic Pancreatitis (AHRI-PEP).

Although rectal administration of nonsteroidal anti-inflammatory drugs is recommended as the standard pharmacologic modality to prevent postendoscopic retrograde cholangiopancreatography (ERCP) post-ERCP pancreatitis (PEP), vigorous periprocedural hydration (vHR) with lactated Ringer's solution (LR) is emerging as an effective prophylaxis modality for PEP. There has been no head-to-head comparison between these 2. This was a single-center, randomized, open-label, noninferiority, parallel-assigned, equal allocation, controlled clinical trial in a tertiary care hospital. Consecutive adults referred for ERCP, satisfying predefined inclusion criteria, underwent simple randomization and blinded allocation into 2 groups. Those allocated to vHR received intravenous LR at 3 mL/kg/h during procedure, 20 ml/kg bolus immediately afterward, and then at 3 mL/kg/h for another 8 hours. Those randomized to rectal Indomethacin received only per-rectal 100 mg suppository immediately post-ERCP. Assuming PEP of 9% in Indomethacin arm and noninferiority margin of 4%, we calculated sample size of 171 patients in each arm for 80% power and α-error 5%. Primary outcome was incidence of PEP, within 1 week, as defined by Cotton's criteria. All analysis were done by intention-to-treat. Between October, 2017 to February, 2018, 521 patients were assessed. In all, 352 were enrolled, 178 randomized to vHR, and 174 to per-rectal Indomethacin. Baseline details and ERCP outcomes were not different between 2 groups. PEP occurred in 6 (1.7%) overall, with 1 (0.6%) in hydration arm, and 5 (2.9%) in indomethacin arm; an absolute risk reduction of 2.3% (95% confidence interval: 0.9%-3.5%) and odds ratio of 0.19 (95% confidence interval: 0.02-1.65). Three patients developed severe PEP, all receiving indomethacin. vHR with LR is noninferior to postprocedure per-rectal Indomethacin for PEP prevention (ClinicalTrials.govID:NCT03629600).

Role of N-acetyl cysteine for the prevention of postendoscopic retrograde cholangio-pancreatography pancreatitis

Background: Pancreatitis is one of the common complications of endoscopic retrograde cholangiopancreatography (ERCP) procedure. Pathogenesis of acute pancreatitis is probably the capillary endothelial injury mediated by oxygen-derived free radicals. Different medications and procedures have been used to prevent post-ERCP pancreatitis (PEP) but are of little benefit. N-acetyl cysteine (NAC) is a safe free radical scavenger. The aim of this study was to evaluate prevention of PEP by inhibiting inflammatory intermediates and oxidative stress with NAC.&#x0D; Methods: This quasi-experimental study was carried out at the Department of Gastrointestinal, Hepatobiliary and Pancreatic Disorders (GHPD) of BIRDEM General Hospital, Dhaka, Bangladesh from January 2018 to July 2019. After meeting the eligibility criteria, total 150 candidates for ERCP were enrolled in this study. Patient lists were collected from ERCP procedure room and patients with uneven serial numbers were selected into the N-group who received a colorless solution of 1200 mg NAC (1200 NAC dissolved with 150 cc water) orally 2 h before ERCP and patients with even serial numbers were selected into the P-group who received only 150 cc water. Serum lipase was measured 2 times: at 4 hours and 24 hours after ERCP. Patients who developed PEP were also evaluated for the risk factors of PEP.&#x0D; Results: PEP occurred in 34 patients (22.6%) out of 150 study subjects [mild 20 (13.3%), moderate 13 (8.6%) and severe 1 (0.7%)]. From N-group 17 patients (22.6%) and from P-group 17 patients (22.6%) developed PEP (p value 0.577). Risk factor analysis revealed that the young age group, patients with type-2 diabetes (T2DM) getting insulin, difficult cannulations, injection of contrast into the pancreatic duct and trainee involvement in the procedure were statistically significant. In multivariate analysis, the young age group, patients with T2DM getting insulin and trainee involvement remained the risk factors of PEP.&#x0D; Conclusion: In conclusion, N-acetyl cysteine had no role in the prevention of PEP in this study.&#x0D; BIRDEM Med J 2023; 13(1): 38-43

Determination of the Effectiveness of Epinephrine Spray on the Papillae in Preventing Pancreatitis after Endoscopic Retrograde Cholangiopancreatography.

As the most common complication of endoscopic retrograde cholangiopancreatography (ERCP) is acute pancreatitis, researchers have paid due attention to minimize this complication using various drugs, one of which is epinephrine. Therefore, the present study aimed at evaluating the effectiveness of epinephrine spray on the papilla in preventing post-ERCP pancreatitis (PEP). The present double-blind clinical trial was performed on 164 patients undergoing ERCP. Patients in both groups received 50 mg rectal suppository as usual before ERCP. Then, during ERCP, epinephrine or normal saline was sprayed topically on the major papillae. After the intervention, patients were evaluated in terms of the incidence of PEP. The results of the present study revealed that the incidence of PEP in the epinephrine and control groups was 2.4% and 4.9%, respectively (P > 0.05). There was no significant difference between the two groups in terms of the incidence of bleeding after ERCP, number of accidental pancreatic duct cannulation, the increase in vision during common bile duct cannulations, the need for precut sphincterotomy, and the number of hospitalization days (P > 0.05). In addition, the chance of developing PEP was lower and higher in patients with higher ages (odds ratio [OR]: 0.86; P = 0.030) and biliary sludge (OR: 4.97; P = 0.042), respectively. As compared with indomethacin alone (control group), it seems that the administration of epinephrine can be effective in reducing the incidence of PEP, although this relationship was not recognized to be significant in this study and only the age and the presence of sludge had a negative and positive relationship with the incidence of PEP, respectively.

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.

Evaluation of direct epinephrine injection into the major papilla in the prevention of post ERCP pancreatitis

Giriş ve Amaç: Akut pankreatit, endoskopik retrograd kolanjiyopankreatografinin en yaygın komplikasyonudur. Dikkate değer morbidite ve mortalite oranlarına sahiptir. Bu çalışmanın amacı, tek başına lokal epinefrin uygulamasının endoskopik retrograd kolanjiyopankreatografi sonrası pankreatit sıklığını ve şiddetini azaltmadaki etkisini araştırmaktır. Gereç ve Yöntem: Endoskopik retrograd kolanjiyopankreatografi yapılan 979 hastanın verileri retrospektif olarak değerlendirildi. Yaş, cinsiyet, endoskopik retrograd kolanjiyopankreatografi endikasyonları, tekniği, endoskopik retrograd kolanjiyopankreatografi sonrası pankreatit riskini artıran durumlar, endoskopik retrograd kolanjiyopankreatografi sonrası pankreatit varlığı ve şiddeti, serum amilaz, lökosit ve C-reaktif protein seviyeleri (öncesi ve sonrası) kaydedildi. Veriler sadece lokal epinefrin profilaksisi alan 473 hasta ve almayan 506 hasta olmak üzere iki grup arasında karşılaştırıldı. Bulgular: Tüm hastalar arasında endoskopik retrograd kolanjiyopankreatografi sonrası pankreatit oranı %6.8, yüksek riskli hasta grubunda ise %13.6 olarak saptandı. Lokal epinefrin profilaksisi alan grupta, almayan gruba göre endoskopik retrograd kolanjiyopankreatografi sonrası pankreatit daha az görüldü (%9.1’e karşı %4.4; p = 0.004). Epinefrin grubunda endoskopik retrograd kolanjiyopankreatografi sonrası amilaz, lökosit ve C-reaktif protein düzeyleri epinefrin almayan gruba göre anlamlı olarak düşük saptandı (p = 0.001, p = 0.004, p = 0.001). Epinefrin grubunda daha az sıklıkla şiddetli ve orta derecede şiddetli pankreatit görüldü (p = 0.003). Yüksek riskli hasta grubunda lokal epinefrin irrigasyonunun endoskopik retrograd kolanjiyopankreatografi sonrası pankreatit oranını düşürdüğü gözlendi (%18.9’a karşı %7.9; p = 0.002). Sonuç: Majör papillaya direkt püskürtme yöntemi ile epinefrin irrigasyonu endoskopik retrograd kolanjiyopankreatografi sonrası pankreatitin önlenmesinde uygulaması kolay, güvenli ve ümit verici bir yöntemdir. Etkinliğini araştırmak için geniş popülasyonlarla daha fazla çalışmaya ihtiyaç vardır.

An Insight on Pharmacological and Mechanical Preventive Measures of Post-ERCP PANCREATITIS (PEP)—A Review

Pancreatitis is the most common complication following endoscopic retrograde cholangio-pancreatography (ERCP). With the progress of research in many drugs and technologies, promising efficacy has been achieved in preventing post-ERCP pancreatitis (PEP). Recently, combined prevention has received more attention in order to further reduce the incidence of PEP. However, there is no review about the combined prevention of PEP. This review summarizes the medication and ERCP techniques that are used to prevent PEP and emphasizes that appropriate combination prevention approaches should be based on risk stratification.

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.

Pre-emptive hydration with lactated Ringer's solution could reduce the incidence of post-endoscopic retrograde cholangiopancreatography pancreatitis in at-risk patients: Propensity score-matched analysis.

This study aimed to investigate the efficacy of intensive fluid-loading therapy post-endoscopic retrograde cholangiopancreatography (ERCP) for the prevention of post-ERCP pancreatitis (PEP) in at-risk patients. In this retrospective study, data of 1200 patients at risk for PEP were investigated. After propensity score matching, 404 patients were included in the normal (n=202) and hydration (n=202) groups. On the day of ERCP, patients in both groups were infused with 2000 ml/24 h of fluid before ERCP. Meanwhile, the hydration group received an additional 1000 ml/10h of lactated Ringer's solution postoperatively. The incidence of PEP was lower in the hydration group (12.4%) than in the normal group (24.3%) (odds ratio [OR]: 0.44; 95% CI: 0.26-0.75, p=.003). The incidence of severe PEP was 2.0% and 6.9% in the hydration and normal groups (OR: 0.27; 95% CI: 0.09-0.84, p=.027), respectively. The incidence of fatal PEP was 0% and 2.0% in the hydration and normal groups (OR: N.A.: p=.123), respectively. Post-ERCP hydration may be an effective method of preventing PEP, including severe PEP, in at-risk patients.

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.

Preventive effect of tacrolimus on patients with post-endoscopic retrograde cholangiopancreatography pancreatitis.

Background/AimsIn patients undergoing endoscopic retrograde cholangiopancreatography (ERCP), calcineurin activates zymogen, which results in pancreatitis. In this study, we aimed to determine the efficacy of tacrolimus, a calcineurin inhibitor, in preventing post-ERCP pancreatitis (PEP). MethodsThis was a prospective pilot study in which patients who underwent ERCP received tacrolimus (4 mg in two divided doses); this was the Tac group. A contemporaneous cohort of patients was included as a control group. All patients were followed-up for PEP. PEP was characterized by worsening abdominal pain with an acute onset, elevated pancreatic enzymes, and a duration of hospital stay of more than 48 hours. Serum tacrolimus levels were measured immediately before the procedure in the Tac group. ResultsThere were no differences in the baseline characteristics between the Tac group (n=48) and the control group (n=51). Only four out of 48 patients (8.3%) had PEP in the Tac group compared to eight out of 51 patients (15.7%) who had PEP in the control group. The mean trough tacrolimus level in patients who developed PEP was significantly lower (p<0.05). ConclusionsOral tacrolimus at a cumulative dose of 4 mg safely prevents PEP. Further randomized controlled studies are warranted to establish the role of tacrolimus in this context.

Rectal INdomethacin, oral TacROlimus, or their combination for the prevention of post-ERCP pancreatitis (INTRO Trial): Protocol for a randomized, controlled, double-blinded trial

BackgroundAcute pancreatitis remains the most common and morbid complication of endoscopic retrograde cholangiopancreatography (ERCP). The use of rectal indomethacin and pancreatic duct stenting has been shown to reduce the incidence and severity of post-ERCP pancreatitis (PEP), but these interventions have limitations. Recent clinical and translational evidence suggests a role for calcineurin inhibitors in the prevention of pancreatitis, with multiple retrospective case series showing a reduction in PEP rates in tacrolimus users. MethodsThe INTRO trial is a multicenter, international, randomized, double-blinded, controlled trial. A total of 4,874 patients undergoing ERCP will be randomized to receive either oral tacrolimus (5 mg) or oral placebo 1–2 h before ERCP, and followed for 30 days post-procedure. Blood and pancreatic aspirate samples will also be collected in a subset of patients to quantify tacrolimus levels. The primary outcome of the study is the incidence of PEP. Secondary endpoints include the severity of PEP, ERCP-related complications, adverse drug events, length of hospital stay, cost-effectiveness, and the pharmacokinetics, pharmacodynamics, and pharmacogenomics of tacrolimus immune modulation in the pancreas. ConclusionsThe INTRO trial will assess the role of calcineurin inhibitors in PEP prophylaxis and develop a foundation for the clinical optimization of this therapeutic strategy from a pharmacologic and economic standpoint. With this clinical trial, we hope to demonstrate a novel approach to PEP prophylaxis using a widely available and well-characterized class of drugs. Trial registrationNCT05252754, registered on February 14, 2022.

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.

Nafamostat Mesylate in the Prevention of Post-endoscopic Retrograde Cholangiography Pancreatitis: A Meta-analysis

Previous evidence from observational studies showed that Nafamostat mesylate (NM) was effective in post-ERCP pancreatitis prevention. We aimed to assess full-text prospective studies on the role of NM in post-ERCP pancreatitis prevention. We searched the PubMed, Medline, and Google Scholar databases for relevant articles during the period from 2009 to November 2020 and updated on March 2022. No restriction regarding the language of publication. The keywords nafamostat mesylate, post-ERCP pancreatitis, prevention, and role were used. A total of 113 studies were identified through the database search, and eight studies (all were published in Asia) met the inclusion criteria for the systematic review. There were five control trials (four randomized and one comparative) and three case-control studies, (3186 patients included. In the present meta-analysis, seven studies concluded the benefit of nafamostat mesylate in the prevention of post-ERCP pancreatitis, and one showed no benefit. The overall effect was highly significant, odd ratio, 0.51, 95%CI=0.38-0.70, P-value=0.0001, heterogeneity=0.17%, P-value for heterogeneity=0.30, I2=17%. Nafamostat mesylate might be effective in post-ERCP pancreatitis prevention. Larger randomize multi-center studies investigating the effectiveness in combination with other preventive measures are needed.

Combined rectal indomethacin and intravenous saline hydration in post-ERCP pancreatitis prophylaxis

Background and study aimAcute pancreatitis (AP) is a potentially life-threatening complication of endoscopic retrograde cholangiopancreatography (ERCP). There is a lack of effective measures to prevent post-ERCP pancreatitis (PEP), except NSAIDs. Aggressive hydration for AP can be considered, given the frequency of hemoconcentration, hypovolemia, and hypoperfusion in pancreatitis. We aimed to clarify the clinical utility of combined indomethacin and saline hydration for preventing PEP. Patients and methodIn this cross-sectional study, 120 patients undergoing ERCP for the first time at the Gastrointestinal Endoscopy Unit and Liver Unit Kasralainy (GIELUKA) were enrolled and then randomly allocated into two groups: indomethacin and indomethacin-hydration groups. Intravenous (IV) saline was given to the latter at a rate of 10 ml/kg/h after the ERCP for 2 h. ResultsThe age of the studied patients was 43.8 ± 14.9 years, with 55% of them being female. The patient-related risk factors for PEP were older age (p = 0.039), higher pre-ERCP urea level (p = 0.032), and less choledocholithiasis (p = 0.028). The patients with PEP had a higher frequency of biliary cannulation attempts (p = 0.004) and accidental pancreatic duct cannulation (p = 0.003), required a longer cannulation time (p = 0.021), had undergone precut knife and transpancreatic sphincterotomy at a higher rate (p = 0.032; and p = 0.001, respectively), and had a significantly longer procedure time (p = 0.006).PEP occurred in only five patients in the indomethacin group, while it did not occur in the indomethacin-hydration group (8% vs. 0%, p = 0.022). Serum amylase and lipase elevation 2 h after ERCP were predictors of PEP. However, serum amylase only was significantly lower 2 h post-ERCP in the indomethacin-hydration group than in the indomethacin group (p = 0.045). Moreover, abdominal pain and vomiting on the first day of ERCP were good predictors of PEP. ConclusionAggressive IV saline hydration with rectal indomethacin can more effectively prevent PEP than indomethacin alone.

Post-Endoscopic Retrograde Cholangiopancreatography Pancreatitis: What We Already Know.

Acute pancreatitis is the most common serious complication of endoscopic retrograde cholangiopancreatography (ERCP) resulting in significant morbidity and occasional mortality. Post-ERCP pancreatitis (PEP) has been recognized since ERCP was first performed, and many studies have shown a consistent risk that must be balanced against the many benefits of this procedure. This review will discuss the pathogenesis, epidemiology, potential risk factors, and clinical presentation of PEP. Moreover, it will discuss in detail the most recent updates of PEP prevention and management.