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Kang X, Xia M, Wang J, Wang X, Luo H, Qin W, Liang Z, Zhao G, Yang L, Sun H, Tao J, Ning B, Zhong L, Zhang R, Ma X, Zhao J, Yue L, Jin H, Kang C, Ren G, Liang S, Wang H, Wang L, Nie Y, Wu K, Fan DM, Pan Y. Rectal diclofenac versus indomethacin for prevention of post-ERCP pancreatitis (DIPPP): a multicentre, double-blind, randomised, controlled trial. Gut 2025; 74:1094-1102. [PMID: 40113243 DOI: 10.1136/gutjnl-2024-334466] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/03/2024] [Accepted: 02/02/2025] [Indexed: 03/22/2025]
Abstract
BACKGROUND Recent meta-analyses suggested diclofenac may be superior to indomethacin in preventing post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP). The aim of our study was to compare the efficacy of 100 mg rectal indomethacin versus diclofenac on PEP incidences. DESIGN This multicentre, double-blinded, randomised controlled trial was conducted in nine tertiary centres in China. Patients with low and high risk for PEP and native papilla were randomly allocated (1:1) to receive 100 mg diclofenac or 100 mg indomethacin rectally before ERCP. The primary outcome was the occurrence of PEP defined by the Cotton consensus. The intention-to-treat principle was conducted for the analysis. RESULTS The trial was terminated early for futility after the predetermined first interim analysis. Between June 2023 and May 2024, 1204 patients were randomised into the diclofenac group (n=600) or indomethacin group (n=604). Baseline characteristics were balanced. The primary outcome occurred in 53 patients (8.8%) of 600 patients allocated to the diclofenac group and 37 patients (6.1%) of 604 patients allocated to the indomethacin group (relative risk 1.44; 95% CI 0.96 to 2.16, p=0.074). PEP occurred in 35 (14.2%) of 247 high-risk patients in the diclofenac group and 26 (9.8%) of 266 high-risk patients in the indomethacin group (p=0.124). PEP incidences were also comparable in low-risk patients between the two groups (18/353 (5.1%) vs 11/338 (3.3%), p=0.227). Other ERCP-related complications did not differ between the two groups. CONCLUSION Pre-procedure 100 mg rectal diclofenac was not superior to the same dose of rectal indomethacin regarding preventing PEP. These findings supported current clinical practice guidelines of 100 mg indomethacin or diclofenac for PEP prophylaxis in patients without contraindications. TRIAL REGISTRATION NUMBER ClinicalTrials.gov (NCT05947461).
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Affiliation(s)
- Xiaoyu Kang
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, Shaanxi, China
| | - Mingxing Xia
- Department of Gastroenterology and Endoscopy, Eastern Hepatobiliary Surgery Hospital, National Center for Liver Cancer, Second Military Medical University, Shanghai, China
| | - Jun Wang
- Department of Gastroenterology, The 986th Hospital of Xijing Hospital, Fourth Militrary Medical University, Xian, China
| | - Xiangping Wang
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, Shaanxi, China
| | - Hui Luo
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, Shaanxi, China
| | - Wenhao Qin
- Department of Gastroenterology and Endoscopy, Eastern Hepatobiliary Surgery Hospital, National Center for Liver Cancer, Second Military Medical University, Shanghai, China
| | - Zirong Liang
- Department of Gastroenterology, The 986th Hospital of Xijing Hospital, Fourth Militrary Medical University, Xian, China
| | - Gang Zhao
- Department of Gastroenterology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China
| | - Longbao Yang
- Department of Gastroenterology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China
| | - Hao Sun
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China
| | - Jie Tao
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China
| | - Bo Ning
- Department of Gastroenterology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Li Zhong
- Department of Gastroenterology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Rongchun Zhang
- Department of Gastroenterology, Hongai Hospital, Xiamen, Fujian, China
| | - Xuyuan Ma
- Department of Gastroenterology, Hongai Hospital, Xiamen, Fujian, China
| | - Jianghai Zhao
- Department of Gastroenterology, Huaihe Hospital of Henan University, Kaifeng, Henan, China
| | - Laifu Yue
- Department of Gastroenterology, Huaihe Hospital of Henan University, Kaifeng, Henan, China
| | - Haifeng Jin
- Department of Gastroenterology, The 980th Hospital of the PLA Joint Logistics Support Force (Primary Bethune International Peace Hospital of PLA), Shijiazhuang, Hebei, China
| | - Chenxi Kang
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, Shaanxi, China
| | - Gui Ren
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, Shaanxi, China
| | - Shuhui Liang
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, Shaanxi, China
| | - Haiying Wang
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, Shaanxi, China
| | - Ling Wang
- Department of Health Statistics, School of Preventive Medicine, Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, Fourth Military Medical University, Xi'an, Shaanxi, China
| | - Yongzhan Nie
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, Shaanxi, China
| | - Kaichun Wu
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, Shaanxi, China
| | - Dai-Ming Fan
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, Shaanxi, China
| | - Yanglin Pan
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, Shaanxi, China
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Sadeghi A, Samar H, Abbasinazari M, Mohammadi P, Abazarikia A, Ziaie S. Efficacy of 2-Mercaptoethane Sulfonate Sodium (MESNA) in the Prevention of Pancreatitis After Endoscopic Retrograde Cholangiopancreatography: A Randomized Open Label Trial. JGH Open 2025; 9:e70083. [PMID: 39834905 PMCID: PMC11743974 DOI: 10.1002/jgh3.70083] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2024] [Revised: 12/01/2024] [Accepted: 12/09/2024] [Indexed: 01/22/2025]
Abstract
Background and Aim Oxidative stress has been considered a factor in the development of post-endoscopic retrograde cholangiopancreatography pancreatitis (PEP). The present clinical trial evaluated whether adding intravenous mesna to rectal indomethacin could prevent or alleviate PEP. Methods An open-labeled clinical trial was done on 698 participants undergoing endoscopic retrograde cholangiopancreatography (ERCP). Eligible patients received 100 mg indomethacin suppository 30 min before undergoing ERCP. Randomly, the participants received 400 mg intravenous mesna or nothing 30 min before doing the procedure. The PEP incidence and degree were measured in the patients as the main outcome. Results The total rate of PEP was equal to 13.7%. No significant difference was seen in the rate and severity of PEP between the mesna plus indomethacin and indomethacin alone arms (14% vs. 13.4%, respectively, p = 0.671). In high-risk patients, PEP rate and severity were lower in the mesna plus indomethacin group compared with indomethacin alone group and the statistical analysis showed that the difference was significant (41.7% vs. 51.8%, respectively, p = 0.033). Conclusion In high-risk patients undergoing ERCP, a combination of intravenous mesna plus rectal indomethacin may decrease the PEP rate and severity.
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Affiliation(s)
- Amir Sadeghi
- Gastroenterology and Liver Diseases Research CenterResearch Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical SciencesTehranIran
| | - Hesamoddin Samar
- Department of Clinical PharmacySchool of Pharmacy, Shahid Beheshti University of Medical SciencesTehranIran
| | - Mohammad Abbasinazari
- Anesthesiology Research CenterShahid Beheshti University of Medical SciencesTehranIran
| | - Parvaneh Mohammadi
- Gastroenterology and Liver Diseases Research CenterResearch Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical SciencesTehranIran
| | - Ali Abazarikia
- Department of Clinical PharmacySchool of Pharmacy, Shahid Beheshti University of Medical SciencesTehranIran
| | - Shadi Ziaie
- Department of Clinical PharmacySchool of Pharmacy, Shahid Beheshti University of Medical SciencesTehranIran
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Janssens LP, Yamparala A, Martin J, O'Meara J, Harmsen WS, Sathi T, Lemke E, Abu Dayyeh BK, Bofill-Garcia A, Petersen BT, Storm AC, Topazian M, Vargas EJ, Chandrasekhara V, Law RJ. Incidence of Post-ERCP Pancreatitis in Patients Receiving Rectal Indomethacin vs. Compounded Rectal Diclofenac Prophylaxis. Dig Dis Sci 2024; 69:3970-3978. [PMID: 39215866 DOI: 10.1007/s10620-024-08604-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/23/2024] [Accepted: 08/18/2024] [Indexed: 09/04/2024]
Abstract
BACKGROUND AND AIMS Endoscopic retrograde cholangiopancreatography (ERCP) carries a 3-15% risk of post-ERCP pancreatitis (PEP). Rectal indomethacin reduces the risk of PEP, but its cost has increased more than 20-fold over the past decade. Rectal diclofenac is also used to prevent PEP but is not commercially available in the United States. The aim of this study is to compare the incidence of PEP after administration of commercially available rectal indomethacin versus compounded rectal diclofenac and assess financial implications. METHODS ERCP cases at our institution with administration of 100 mg rectal indomethacin or 100 mg compounded rectal diclofenac between May 2018 and January 2022 were retrospectively reviewed. The incidence and severity of PEP was compared between the indomethacin (n = 728) and diclofenac (n = 304) groups. Risk factors (young age, female sex, history of pancreatitis or PEP, sphincterotomy during procedure, pancreatic indication, trainee involvement) and protective factors (prior sphincterotomy, pancreatic duct stenting) for PEP were compared between groups. RESULTS 60 patients (8.2%) in the rectal indomethacin group and 25 patients (8.2%) in the compounded rectal diclofenac group developed PEP, resulting in moderate or severe PEP in 9 (15.0%) and 2 (8.0%) patients, respectively. The compounded rectal diclofenac group had more trainee involvement (46.1% vs. 32.8%, p = 0.0001) and more prior sphincterotomy cases (15.8% vs. 10.6%, p = 0.0193) compared to the rectal indomethacin group; no statistically significant differences were observed in all other risk and protective factors. Following switch to compounded rectal diclofenac, institutional annual cost savings amounted to $441,460.62 and patient charge decreased 45-fold. CONCLUSION This retrospective single-center real-world analysis showed similar efficacy of rectal indomethacin and compounded rectal diclofenac in preventing PEP but demonstrates substantial cost savings after switching to compounded rectal diclofenac.
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Affiliation(s)
- Laurens P Janssens
- Department of Gastroenterology and Hepatology, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA
| | - Aishwarya Yamparala
- Department of Gastroenterology and Hepatology, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA
| | - John Martin
- Department of Gastroenterology and Hepatology, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA
| | - John O'Meara
- Department of Pharmacy, Mayo Clinic, Rochester, MN, USA
| | - William S Harmsen
- Department of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN, USA
| | - Thanmay Sathi
- Department of Gastroenterology and Hepatology, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA
| | - Elizabeth Lemke
- Department of Gastroenterology and Hepatology, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA
| | - Barham K Abu Dayyeh
- Department of Gastroenterology and Hepatology, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA
| | - Aliana Bofill-Garcia
- Department of Gastroenterology and Hepatology, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA
| | - Bret T Petersen
- Department of Gastroenterology and Hepatology, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA
| | - Andrew C Storm
- Department of Gastroenterology and Hepatology, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA
| | - Mark Topazian
- Department of Gastroenterology and Hepatology, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA
| | - Eric J Vargas
- Department of Gastroenterology and Hepatology, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA
| | - Vinay Chandrasekhara
- Department of Gastroenterology and Hepatology, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA
| | - Ryan J Law
- Department of Gastroenterology and Hepatology, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA.
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Rojas-Victoria EJ, Hernández-Ruiz SI, García-Perdomo HA. Effectiveness of the pharmacological therapy to prevent post ERCP acute pancreatitis: a network meta-analysis. Expert Rev Gastroenterol Hepatol 2024; 18:203-215. [PMID: 38725175 DOI: 10.1080/17474124.2024.2345640] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/02/2023] [Accepted: 04/17/2024] [Indexed: 05/24/2024]
Abstract
OBJECTIVE To determine the effectiveness of the different pharmacological agents in preventing post-ERCP acute pancreatitis. METHODS We included clinical trials of pharmacological interventions for prophylaxis of acute post-ERCP pancreatitis. The event evaluated was acute pancreatitis. We conducted a search strategy in MEDLINE (OVID), EMBASE, and Cochrane Central Register of Controlled Trials from inception to nowadays. We reported the information in terms of relative risks (RR) with a 95% confidence interval. We assessed the heterogeneity using the I2 test. RESULTS We included 84 studies for analysis (30,463 patients). The mean age was 59.3 years (SD ± 7.01). Heterogeneity between studies was low (I2 = 34.4%) with no inconsistencies (p = 0.2567). Post ERCP pancreatitis was less in prophylaxis with NSAIDs (RR 0.65 95% CI [0.52 to 0.80]), aggressive hydration with Lactate Ringer (RR 0.32 95% CI [0.12-0.86]), NSAIDs + isosorbide dinitrate (RR 0.28 95% CI [0.11-0.71]) and somatostatin and analogues (RR 0.54 [0.43 to 0.68]) compared with placebo. CONCLUSIONS NSAIDs, the Combination of NSAIDs + isosorbide dinitrate, somatostatin and analogues, and aggressive hydration with lactate ringer are pharmacological strategies that can prevent post-ERCP pancreatitis when compared to placebo. More clinical trials are required to determine the effectiveness of these drugs.
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Affiliation(s)
| | | | - Herney Andrés García-Perdomo
- Division of Urology/Urooncology, Department of Surgery, School of Medicine, Universidad del Valle, Cali, Colombia
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Xie Y, Cheng Z, Deng C, Deng M, Zhang H. Nafamostat mesilate for prevention of post-endoscopic retrograde cholangiopancreatography pancreatitis: A systematic review and meta-analysis based on prospective, randomized, and controlled trials. Medicine (Baltimore) 2023; 102:e35174. [PMID: 37832051 PMCID: PMC10578773 DOI: 10.1097/md.0000000000035174] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/23/2023] [Accepted: 08/21/2023] [Indexed: 10/15/2023] Open
Abstract
OBJECTIVES To evaluate the efficacy of nafamostat mesilate in the prevention of post-endoscopic retrograde cholangiopancreatography pancreatitis (PEP) by conduct a systematic review and meta-analysis. METHOD We retrieved for all randomized controlled trials (RCTs) about compare nafamostat mesilate with placebo in preventing PEP published before August 23, 2022, in 5 major electronic databases. The primary outcome was PEP rate, and the secondary outcome was post-ERCP hyperamylasemia (PEHA) rate. Subgroup analyses were performed to reveal the factors that may affect the preventive effect of nafamostat. Assessment of the quality of evidence was conducted based on Grading of Recommendations, Assessment, Development and Evaluations (GRADE) system. RESULTS According to the search strategy and criteria of inclusion and exclusion, 8 articles with a number of 3210 patients were included. The PEP incidence of the nafamostat group was inferior compared with the placebo group (4.6% vs 8.5%, RR = 0.50, 95% CI: 0.38-0.66). Subgroup analyses revealed that nafamostat had a preventive effect on patients with different risk stratification (High-risk: RR = 0.61, 95% CI: 0.43-0.86, Low-risk: RR = 0.28; 95% CI: 0.17-0.47). Different doses (20 mg: RR = 0.50, 95% CI: 0.36-0.69, 50 mg: RR = 0.45, 95% CI: 0.27-0.74) and duration (<12 hour: RR = 0.55, 95% CI: 0.37-0.81, ≥12 h: RR = 0.44, 95% CI: 0.29-0.66) of administration of nafamostat are adequate for the prevention of PEP, but postoperative administration may not help (preoperative: RR = 0.52, 95% CI: 0.39-0.69, postoperative: RR = 0.54, 95% CI: 0.23-1.23). Nafamostat may not efficacious in preventing severe PEP (Mild: RR = 0.49, 95% CI, 0.35-0.68, Moderate: RR = 0.47, 95% CI: 0.25-0.86, Severe: RR = 0.91, 95% CI, 0.25-3.29) or in low-quality studies (Low-quality: RR = 0.69, 95% CI: 0.13-3.60, High-quality: RR = 0.49, 95% CI: 0.37-0.65). CONCLUSION Preoperative use of nafamostat can effectively prevent PEP in patients with various risk stratification. Nafamostat can prevent mild and moderate PEP, but may not prevent severe PEP and PEHA. There should be more high-quality RCTs in future to strengthen the evidence of nafamostat in preventing PEP.
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Affiliation(s)
- Yu Xie
- Department of Infectious Diseases, The Affiliated Hospital of Southwest Medical University, Luzhou, China
| | - Ziyao Cheng
- Department of Gastroenterology, The Affiliated Hospital of Southwest Medical University, Luzhou, China
| | - Cunliang Deng
- Department of Infectious Diseases, The Affiliated Hospital of Southwest Medical University, Luzhou, China
| | - Mingming Deng
- Department of Gastroenterology, The Affiliated Hospital of Southwest Medical University, Luzhou, China
| | - Hailong Zhang
- Department of Gastroenterology, The Affiliated Hospital of Southwest Medical University, Luzhou, China
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Sadeghi A, Jafari-Moghaddam R, Ataei S, Asadiafrooz M, Abbasinazari M. Role of vitamin C and rectal indomethacin in preventing and alleviating post-endoscopic retrograde cholangiopancreatography pancreatitis: a clinical study. Clin Endosc 2023; 56:214-220. [PMID: 37013392 PMCID: PMC10073861 DOI: 10.5946/ce.2022.165] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/05/2022] [Accepted: 06/27/2022] [Indexed: 04/05/2023] Open
Abstract
BACKGROUND/AIMS This study aimed to determine whether vitamin C in addition to indomethacin decreases the occurrence and severity of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) occurrence and severity. METHODS This randomized clinical trial included patients undergoing ERCP. The participants were administered either rectal indomethacin (100 mg) plus an injection of vitamin C (500 mg) or rectal indomethacin (100 mg) alone just before ERCP. The primary outcomes were PEP occurrence and severity. The secondary amylase and lipase levels were determined after 24 hours. RESULTS A total of 344 patients completed the study. Based on intention-to-treat analysis, the PEP rates were 9.9% for indomethacin plus vitamin C plus indomethacin and 15.7% for indomethacin alone. Regarding the per-protocol analysis, the PEP rates were 9.7% and 15.7% in the combination and indomethacin arms, respectively. There was a remarkable difference between the two arms in PEP occurrence and severity on intention-to-treat and per-protocol analyses (p=0.034 and p=0.031, respectively). The post-ERCP lipase and amylase concentrations were lower in the combination arm than in the indomethacin alone arm (p=0.034 and p=0.029, respectively). CONCLUSION Vitamin C injection in addition to rectal indomethacin reduced PEP occurrence and severity.
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Affiliation(s)
- Amir Sadeghi
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Rana Jafari-Moghaddam
- Department of Clinical Pharmacy, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Sara Ataei
- Department of Clinical Pharmacy, School of Pharmacy, Hamadan University of Medical Sciences, Hamadan, Iran
| | - Mahboobe Asadiafrooz
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mohammad Abbasinazari
- Department of Clinical Pharmacy, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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Kang X, Guo X, Chen Z, Zhou Z, Luo H, Lu Y, Lou L, Guo X, Pan Y. The Incidence and Severity of Post-ERCP Pancreatitis in Patients Receiving Standard Administration of NSAIDs: a Systematic Review and Meta-analysis. J Gastrointest Surg 2022; 26:2380-2389. [PMID: 35941494 DOI: 10.1007/s11605-022-05399-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/27/2022] [Accepted: 05/14/2022] [Indexed: 01/31/2023]
Abstract
BACKGROUND Routine rectal administration of 100 mg of diclofenac or indomethacin was demonstrated to be an effective prevention method to prevent post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis. The systematic review and meta-analysis aimed to estimate the incidence and severity of post-ERCP pancreatitis (PEP) and explore the discrepancies of PEP incidences among different subgroups. METHODS The PubMed, Web of Science, and Ovid EMBASE databases were searched for studies published until December 2020. Only randomized controlled trials (RCTs) reported rectal administration of 100 mg or higher doses of diclofenac or indomethacin, with PEP as the primary outcomes were eligible for inclusion. The overall and severity of PEP were estimated. Subgroup analysis was performed based on geographic regions, risk level, study beginning time, type of NSAIDs, administration time, and sample size. RESULTS There were 26 randomized controlled trials (RCTs) with 7954 patients in 31 NSAIDs arms. The pooled incidences were 7.2% for overall PEP (95% confidence interval (CI) 5.9-8.5%), 5.0% for mild PEP (95% CI, 4.0-6.0%), and 1.5% for moderate and severe PEP (0.8-2.3%). PEP rate were higher in patients receiving rectal indomethacin than that of patients receiving rectal diclofenac (7.8% (95% CI, 6.4-9.3%) vs 3.8% (95% CI, 2.2-5.3%), p = 0.009). The PEP rates of high-risk patients and average-risk patients were 8.9% (95% CI, 5.6-12.2%) and 6.4% (95% CI, 5.1-7.6%), respectively (p = 0.160). CONCLUSIONS The incidence of PEP was higher in patients receiving 100 mg rectal indomethacin than patients receiving 100 mg diclofenac. The effect of 100 mg diclofenac versus indomethacin on preventing PEP requires further study.
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Affiliation(s)
- Xiaoyu Kang
- State Key Laboratory of Cancer Biology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, Shaanxi, People's Republic of China
| | - Xiaoyang Guo
- State Key Laboratory of Cancer Biology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, Shaanxi, People's Republic of China.,Department of Ultrasound, The 305 Hospital of PLA, Bejing, People's Republic of China
| | - Zhangqian Chen
- State Key Laboratory of Cancer Biology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, Shaanxi, People's Republic of China.,Department of Infectious Diseases, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, People's Republic of China
| | - Zhirui Zhou
- Radiation Oncology Center, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China
| | - Hui Luo
- State Key Laboratory of Cancer Biology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, Shaanxi, People's Republic of China
| | - Yajie Lu
- Department of Oncology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, People's Republic of China
| | - Lijun Lou
- State Key Laboratory of Cancer Biology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, Shaanxi, People's Republic of China
| | - Xuegang Guo
- State Key Laboratory of Cancer Biology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, Shaanxi, People's Republic of China
| | - Yanglin Pan
- State Key Laboratory of Cancer Biology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, Shaanxi, People's Republic of China.
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McKee K, Singh VK, Akshintala VS. Rectal Nonsteroidal Anti-inflammatory Drugs for Post-Endoscopic Retrograde Cholangiopancreatography Pancreatitis Prophylaxis: A Case Study in a Price-Escalation Era. Gastroenterology 2022; 163:543-546. [PMID: 35598627 DOI: 10.1053/j.gastro.2022.05.026] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/30/2021] [Revised: 03/11/2022] [Accepted: 05/12/2022] [Indexed: 12/02/2022]
Affiliation(s)
- Katherine McKee
- Department of Engineering, University of Maryland, College Park, Maryland
| | - Vikesh K Singh
- Division of Gastroenterology, Johns Hopkins Medical Institutions, Baltimore, Maryland
| | - Venkata S Akshintala
- Division of Gastroenterology, Johns Hopkins Medical Institutions, Baltimore, Maryland; Department of Gastroenterology, Asian Institute of Gastroenterology, Hyderabad, India
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Shi QQ, Huang GX, Li W, Yang JR, Ning XY. Rectal nonsteroidal anti-inflammatory drugs, glyceryl trinitrate, or combinations for prophylaxis of post-endoscopic retrograde cholangiopancreatography pancreatitis: A network meta-analysis. World J Clin Cases 2022; 10:7859-7871. [PMID: 36158503 PMCID: PMC9372852 DOI: 10.12998/wjcc.v10.i22.7859] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/10/2021] [Revised: 12/04/2021] [Accepted: 07/06/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Acute 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.
AIM To compare NSAIDs and GTN for prevention of PEP and to determine whether they are better in combination.
METHODS A 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/).
RESULTS Twenty-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%).
CONCLUSION Combination of rectal indomethacin 100 mg with sublingual GTN offered better prevention of PEP than when used alone and could alleviate the severity of PEP.
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Affiliation(s)
- Qing-Qing Shi
- Department of Health Management Center, The People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Guo-Xiu Huang
- Department of Health Management Center, The People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Wei Li
- Department of Health Management Center, The People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Jian-Rong Yang
- Department of Hepatobiliary, Pancreas and Spleen Surgery, The People's Hospital of Guangxi Zhuang Autonomous Region, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Xiao-Yi Ning
- Department of Hematology, The Frist People’s Hospital of Nanning, Nanning 530021, Guangxi Zhuang Autonomous Region, China
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10
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Radadiya D, Brahmbhatt B, Reddy C, Devani K. Efficacy of Combining Aggressive Hydration With Rectal Indomethacin in Preventing Post-ERCP Pancreatitis: A Systematic Review and Network Meta-Analysis. J Clin Gastroenterol 2022; 56:e239-e249. [PMID: 33769395 DOI: 10.1097/mcg.0000000000001523] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/23/2020] [Accepted: 01/29/2021] [Indexed: 12/13/2022]
Abstract
Postendoscopic retrograde cholangiopancreatography pancreatitis (PEP) is the most common complication of endoscopic retrograde cholangiopancreatography pancreatitis (ERCP). No randomized controlled trial (RCT) has compared the efficacy of the American Society of Gastrointestinal Endoscopy and European Society of Gastrointestinal Endoscopy recommended interventions for PEP prevention. We assessed the effectiveness of these interventions using network meta-analysis. PubMed, EMBASE, and Cochrane databases were searched to identify RCTs investigating guideline-recommended interventions and their combinations [rectal nonsteroidal anti-inflammatory drugs (NSAIDs): indomethacin or diclofenac, pancreatic stent (PS), aggressive hydration (AH), sublingual nitrate) for PEP prevention. We performed direct and Bayesian network meta-analysis, and the surface under the cumulative ranking curve to rank interventions. Subgroup network meta-analysis for high-risk populations was also performed. We identified a total of 38 RCTs with 10 different interventions. Each intervention was protective against PEP on direct and network meta-analysis compared with controls. Except AH+diclofenac and NSAIDs+ sublingual nitrate, AH+indomethacin was associated with a significant reduction in risk of PEP compared with PS [odds ratio (OR), 0.09; credible interval (CrI), 0.003-0.71], indomethcin+PS (OR, 0.09; CrI, 0.003-0.85), diclofenac (OR, 0.09; CrI, 0.003-0.65), AH (OR, 0.09; CrI, 0.003-0.65), sublingual nitrate (OR, 0.07; CrI, 0.002-0.63), and indomethacin (OR, 0.06; CrI, 0.002-0.43). AH with either rectal NSAIDs or sublingual nitrate had similar efficacy. AH+indomethacin was the best intervention for preventing PEP with 95.3% probability of being ranked first. For high-risk patients, although the efficacy of PS and indomethacin were comparable, PS had an 80.8% probability of being ranked first. AH+indomethacin seems the best intervention for preventing PEP. For high-risk patients, PS seems the most effective strategy. The potential of combination of interventions need to be explored further.
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Affiliation(s)
| | - Bhaumik Brahmbhatt
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, FL
| | - Chakradhar Reddy
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, East Tennessee State University, Johnson City, TN
| | - Kalpit Devani
- Department of Internal Medicine, Division of Gastroenterology and Liver Disease, Prisma Health, School of Medicine, University of South Carolina, Greenville, SC
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11
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Zhang Q, Deng DH, Liu J, Chen WW, Chen J, Chen CW. Application of non-steroidal anti-inflammatory drugs in prevention of pancreatitis after endoscopic retrograde cholangiopancreatography. Shijie Huaren Xiaohua Zazhi 2022; 30:198-203. [DOI: 10.11569/wcjd.v30.i4.198] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Endoscopic retrograde cholangiopancreatography (ERCP) is one of the most important methods for the clinical diagnosis and treatment of biliary and pancreatic diseases. Post-ERCP pancreatitis (PEP) is the most common complication. Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used in clinical prevention of PEP, but the application standards are not unified. This article reviews the progress in the research of the preventive effect of different types of NSAIDs on PEP, their administration routes, timing, and dosage, and combination with other drugs, as well as the preventive effect of NSAIDs in different risk stratification populations, and points out that indomethacin and diclofenac are the most commonly used types of NSAIDs, which should be given at 100 mg via rectal administration before ERCP in all non-selected patients with no contraindications.
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Affiliation(s)
- Qian Zhang
- Dalian Medical University, Dalian 116000, Liaoning Province, China
| | - Deng-Hao Deng
- Department of Gastroenterology, Subei People's Hospital of Jiangsu Province, Yangzhou 225001, Jiangsu Province, China
| | - Jun Liu
- Department of Gastroenterology, Subei People's Hospital of Jiangsu Province, Yangzhou 225001, Jiangsu Province, China
| | - Wei-Wei Chen
- Department of Gastroenterology, Subei People's Hospital of Jiangsu Province, Yangzhou 225001, Jiangsu Province, China
| | - Juan Chen
- Department of Gastroenterology, Subei People's Hospital of Jiangsu Province, Yangzhou 225001, Jiangsu Province, China
| | - Chao-Wu Chen
- Department of Gastroenterology, Subei People's Hospital of Jiangsu Province, Yangzhou 225001, Jiangsu Province, China
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12
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Yu S, Shen X, Li L, Bi X, Chen P, Wu W. Rectal indomethacin and diclofenac are equally efficient in preventing pancreatitis following endoscopic retrograde cholangiopancreatography in average-risk patients. JGH Open 2021; 5:1119-1126. [PMID: 34621996 PMCID: PMC8485396 DOI: 10.1002/jgh3.12643] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2021] [Accepted: 08/04/2021] [Indexed: 11/22/2022]
Abstract
Rectal indomethacin and diclofenac are promising drugs for prevention of post‐endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP). However, their prophylactic effect on PEP in average‐risk patients remains controversial. We performed a systematic review and meta‐analysis to assess the efficacy and safety of rectal indomethacin and diclofenac in average‐risk patients, and to indirectly compare the prophylactic effect of the two drugs. A comprehensive search of the PubMed, EMBASE, and Cochrane Library databases was performed to identify randomized controlled trials (RCTs) on rectal indomethacin or diclofenac for prophylaxis against PEP. Fixed‐ and random‐effects models weighted by the Mantel–Haenszel method were used for direct comparisons. The adjusted indirect treatment comparison method was used to indirectly compare the efficacy of indomethacin and diclofenac. A total of 10 RCTs, including 2928 patients, met our inclusion criteria. No significant publication bias was identified. Pooled estimates showed that rectal indomethacin and diclofenac were associated with a significant reduction in the overall risk of PEP compared with control intervention [relative risk (RR) = 0.62; 95% confidence interval (CI): 0.46–0.83] in average‐risk patients. Subgroup analyses showed that both rectal indomethacin (RR = 0.67; 95% CI: 0.49–0.94) and diclofenac (RR = 0.42; 95% CI: 0.23–0.75) were effective in the prevention of PEP. Indirect comparison showed no significant difference between the effectiveness of the two drugs in the prevention of PEP (RR = 1.607; 95% CI: 0.824–3.136). The updated meta‐analysis suggests that both drugs provide equivalent protection against PEP in average‐risk patients.
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Affiliation(s)
- Shuang Yu
- Department of Gastroenterology Chongqing University Three Gorges Hospital Chongqing China
| | - Xumu Shen
- Department of Gastroenterology Chongqing University Three Gorges Hospital Chongqing China
| | - Liang Li
- Department of Gastroenterology Chongqing University Three Gorges Hospital Chongqing China
| | - Xiaofei Bi
- Department of Gastroenterology Chongqing University Three Gorges Hospital Chongqing China
| | - Ping Chen
- Department of Gastroenterology Chongqing University Three Gorges Hospital Chongqing China
| | - Wei Wu
- Department of Gastroenterology Chongqing University Three Gorges Hospital Chongqing China
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13
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Akshintala VS, Sperna Weiland CJ, Bhullar FA, Kamal A, Kanthasamy K, Kuo A, Tomasetti C, Gurakar M, Drenth JPH, Yadav D, Elmunzer BJ, Reddy DN, Goenka MK, Kochhar R, Kalloo AN, Khashab MA, van Geenen EJM, Singh VK. 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. Lancet Gastroenterol Hepatol 2021; 6:733-742. [PMID: 34214449 DOI: 10.1016/s2468-1253(21)00170-9] [Citation(s) in RCA: 43] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/14/2021] [Revised: 05/06/2021] [Accepted: 05/07/2021] [Indexed: 02/07/2023]
Abstract
BACKGROUND 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. METHODS 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. FINDINGS 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. INTERPRETATION 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. FUNDING None.
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Affiliation(s)
- Venkata S Akshintala
- Division of Gastroenterology, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
| | | | - Furqan A Bhullar
- Division of Gastroenterology, Johns Hopkins Medical Institutions, Baltimore, MD, USA
| | - Ayesha Kamal
- Division of Gastroenterology, Johns Hopkins Medical Institutions, Baltimore, MD, USA
| | - Kavin Kanthasamy
- Division of Gastroenterology, Johns Hopkins Medical Institutions, Baltimore, MD, USA
| | - Albert Kuo
- Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA
| | - Cristian Tomasetti
- Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA; Division of Biostatistics & Bioinformatics, Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD, USA
| | - Merve Gurakar
- Division of Gastroenterology, Johns Hopkins Medical Institutions, Baltimore, MD, USA
| | - Joost P H Drenth
- Department of Gastroenterology and Hepatology, Radboud University Medical Center, Nijmegen, Netherlands
| | - Dhiraj Yadav
- Division of Gastroenterology and Hepatology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - B Joseph Elmunzer
- Division of Gastroenterology and Hepatology, Medical University of South Carolina, Charleston, SC, USA
| | - D Nageshwar Reddy
- Department of Gastroenterology, Asian Institute of Gastroenterology, Hyderabad, India
| | - Mahesh K Goenka
- Department of Gastroenterology, Apollo Gleneagles Hospital, Kolkata, India
| | - Rakesh Kochhar
- Department of Gastroenterology, Postgraduate Institute of Medical Education & Research, Chandigarh, India
| | - Anthony N Kalloo
- Division of Gastroenterology, Johns Hopkins Medical Institutions, Baltimore, MD, USA
| | - Mouen A Khashab
- Division of Gastroenterology, Johns Hopkins Medical Institutions, Baltimore, MD, USA
| | - Erwin J M van Geenen
- Department of Gastroenterology and Hepatology, Radboud University Medical Center, Nijmegen, Netherlands
| | - Vikesh K Singh
- Division of Gastroenterology, Johns Hopkins Medical Institutions, Baltimore, MD, USA
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14
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Dubravcsik Z, Hritz I, Keczer B, Novák P, Lovász BD, Madácsy L. Network meta-analysis of prophylactic pancreatic stents and non-steroidal anti-inflammatory drugs in the prevention of moderate-to-severe post-ERCP pancreatitis. Pancreatology 2021; 21:704-713. [PMID: 33926821 DOI: 10.1016/j.pan.2021.04.006] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/05/2020] [Revised: 03/30/2021] [Accepted: 04/14/2021] [Indexed: 02/06/2023]
Abstract
BACKGROUND There 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. METHODS We 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. RESULTS Seven 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. CONCLUSION Prophylactic pancreatic stent placement but not rectal NSAID seems to prevent moderate-to-severe PEP better both, in average- and high-risk patients.
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Affiliation(s)
- Zsolt Dubravcsik
- Department of Gastroenterology, BKM Hospital, Kecskemét, Hungary.
| | - István Hritz
- Center for Therapeutic Endoscopy, 1st Department of Surgery, Semmelweis University, Budapest, Hungary
| | - Bánk Keczer
- Center for Therapeutic Endoscopy, 1st Department of Surgery, Semmelweis University, Budapest, Hungary
| | - Péter Novák
- Department of Gastroenterology, BKM Hospital, Kecskemét, Hungary
| | | | - László Madácsy
- Department of Gastroenterology, BKM Hospital, Kecskemét, Hungary; Endo-kapszula Private Medical Center, Székesfehérvár, Hungary
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15
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Mansour-Ghanaei F, Joukar F, Khalesi AA, Naghipour M, Sepehrimanesh M, Mojtahedi K, Yeganeh S, Saedi HS, Asl SF. Naproxen, isosorbide dinitrate and co-administration cannot prevent post-endoscopic retrograde cholangiopancreatography pancreatitis: Randomized controlled trial. Ann Hepatobiliary Pancreat Surg 2020; 24:259-268. [PMID: 32843590 PMCID: PMC7452799 DOI: 10.14701/ahbps.2020.24.3.259] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/08/2020] [Revised: 04/30/2020] [Accepted: 04/30/2020] [Indexed: 11/17/2022] Open
Abstract
Backgrounds/Aims Acute pancreatitis is the most widespread complication of endoscopic retrograde cholangiopancreatography. Here, we investigated the efficacy of rectal suppository naproxen, sublingual isosorbide dinitrate and their co-administration in the prevention of post-ERCP pancreatitis. Methods This double-blind randomized clinical trial carried out from June 2015 to February 2016 at the Gastrointestinal and Liver Diseases Research Center in Rasht, Iran. A total of 585 patients were selected from candidates for diagnostic or therapeutic ERCP by using the simple sampling method. Patients divided into three groups. Group A received 500 mg naproxen, group B took 5 mg isosorbide dinitrate, and group C was co-administrated both agents before ERCP. The primary outcome measure was the development of pancreatitis onset of pain in the upper abdomen and increase of serum amylase activity more than 3 times over the upper normal limit (60-100 IU/L) within first the 24 h post-ERCP. Results Totally, 80 patients developed PEP included 29 (4.9%), 24 (4.1%), and 27 (4.6%) patients in groups A, B, and C, respectively (p=0.845). Longer ERCP time (p=0.041), using diazepam (p=0.033), a higher number of pancreatic ducts cannulation (p<0.001), pancreatic duct injection (p=0.013), and using pancreatic stent (p=0.004) were the predisposing factors for PEP. Conclusions Our findings indicated that prophylactic naproxen suppository or isosorbide dinitrate sublingually or co-administration had no significant difference in the prevention and severity of PEP, however, enhancing the endoscopist’s skills can be effective. Departments and educational hospitals should develop their assessment and quality assurance measures for the training of fellows’ not only technical training but also an understanding of the diagnostic and therapeutic roles of the procedure.
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Affiliation(s)
- Fariborz Mansour-Ghanaei
- GI Cancer Screening and Prevention Research Center, Rasht, Iran.,Caspian Digestive Disease Research Center, Rasht, Iran
| | - Farahnaz Joukar
- GI Cancer Screening and Prevention Research Center, Rasht, Iran.,Gastrointestinal and Liver Diseases Research Center, Guilan University of Medical Sciences, Rasht, Iran
| | | | | | - Masood Sepehrimanesh
- Gastrointestinal and Liver Diseases Research Center, Guilan University of Medical Sciences, Rasht, Iran.,New Iberia Research Center, University of Louisiana, Lafayette, LA, USA
| | - Kourosh Mojtahedi
- Caspian Digestive Disease Research Center, Rasht, Iran.,Gastrointestinal and Liver Diseases Research Center, Guilan University of Medical Sciences, Rasht, Iran
| | - Sara Yeganeh
- GI Cancer Screening and Prevention Research Center, Rasht, Iran.,Gastrointestinal and Liver Diseases Research Center, Guilan University of Medical Sciences, Rasht, Iran
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16
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Ahmad W, Okam NA, Torrilus C, Rana D, Khatun MK, Jahan N. Pharmacological Prevention of Post-Endoscopic Retrograde Cholangiopancreatography Pancreatitis: Where Do We Stand Now? Cureus 2020; 12:e10115. [PMID: 33005532 PMCID: PMC7523742 DOI: 10.7759/cureus.10115] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022] Open
Abstract
Post-endoscopic retrograde cholangiopancreatography pancreatitis (PEP) is the most frequently occurring complication of endoscopic retrograde cholangiopancreatography (ERCP). PEP is associated with significant morbidity and mortality; that is why the prevention of PEP is essential. Pharmacoprevention holds a central position in PEP prophylaxis. The current literature explores the efficacy of various pharmacological agents in preventing PEP, their routes of administration, and the correct administration timing. Data was collected on PubMed using regular keywords, the latter yielded 2077 papers. After applying inclusion and exclusion criteria, 218 papers were selected and screened and 28 studies were finally chosen after the removal of duplicate and irrelevant studies. The selected 28 articles comprised 25 randomized clinical trials and three systematic reviews. The study concludes that rectal non-steroidal anti-inflammatory drugs (NSAIDs) administered before ERCP are effective in preventing PEP in high-risk patients. The efficacy of rectal NSAIDs in low to medium risk group is not well established. A combination of rectal NSAIDs and intravenous hydration provides improved prophylaxis against PEP in high-risk patients than NSAIDs alone. Nafamostat, sublingual nitrates, and intravenous hydration are potential alternatives in patients with contraindications to NSAIDs.
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17
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Yang J, Wang W, Liu C, Zhao Y, Ren M, He S. Rectal Nonsteroidal Anti-Inflammatory Drugs for Endoscopic Retrograde Cholangiopancreatography Postoperative Pancreatitis Prevention: A Network Meta-Analysis. J Clin Gastroenterol 2020; 54:305-313. [PMID: 32011404 DOI: 10.1097/mcg.0000000000001322] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
BACKGROUND Post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) is the most common complication of ERCP procedure. Nonsteroidal anti-inflammatory drugs (NSAIDs) are reported to be one protective pharmacological agent with great efficacy regarding this complication. Recently, more trails have addressed this issue and some inconsistent results appeared. Therefore, this study aims to evaluate the efficacy and safety of different rectal NSAIDs schemes to prevent PEP. MATERIALS AND METHODS Eligible studies published on PubMed, the Cochrane Library, Embase, Web of Science before November 2018 were reviewed, and those which met the inclusion criteria were included in the analysis. The preventions were divided as placebo/no treatment, post-ERCP rectal diclofenac, pre-ERCP rectal diclofenac, post-ERCP rectal indomethacin, pre-ERCP rectal indomethacin, indomethacin using during ERCP, and pre-ERCP rectal naproxen. The main outcomes included the incidence of PEP and its severity. Other complications were also analyzed. RESULTS A total of 23 randomized controlled trials were included. The results of network meta-analysis illustrated that compared with the control, post-ERCP rectal diclofenac, pre-ERCP rectal diclofenac, and indomethacin were significantly associated with lower incidences of PEP. Moreover, it is notable that pre-ERCP rectal NSAIDs might reduce the severity of pancreatitis. Also, rectal NSAIDs may lead to less occurrence of asymptomatic hyperamylasemia. On the basis of the clustered ranking, pre-ERCP diclofenac appeared to be the superior intervention for PEP with satisfying efficacy. CONCLUSIONS The present study showed that pre-ERCP diclofenac is the optimal prevention method for PEP. However, more high quality head-to-head randomized controlled trials and observational studies are expected in the future.
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Affiliation(s)
- Jiahui Yang
- Department of Gastroenterology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an
| | - Wancong Wang
- Department of Gastroenterology, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, People's Republic of China
| | - Chuan Liu
- Department of Gastroenterology, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, People's Republic of China
| | - Yan Zhao
- Department of Gastroenterology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an
| | - Mudan Ren
- Department of Gastroenterology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an
| | - Shuixiang He
- Department of Gastroenterology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an
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Johnson KD, Perisetti A, Tharian B, Thandassery R, Jamidar P, Goyal H, Inamdar S. Endoscopic Retrograde Cholangiopancreatography-Related Complications and Their Management Strategies: A "Scoping" Literature Review. Dig Dis Sci 2020; 65:361-375. [PMID: 31792671 DOI: 10.1007/s10620-019-05970-3] [Citation(s) in RCA: 47] [Impact Index Per Article: 9.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/04/2019] [Accepted: 11/16/2019] [Indexed: 12/12/2022]
Abstract
Endoscopic retrograde cholangiopancreatography (ERCP) is a well-known procedure with both diagnostic and therapeutic utilities in managing pancreaticobiliary conditions. With the advancements of endoscopic techniques, ERCP has become a relatively safe and effective procedure. However, as ERCP is increasingly being utilized for different advanced techniques, newer complications have been noticed. Post-ERCP complications are known, and mostly include pancreatitis, infection, hemorrhage, and perforation. The risks of these complications vary depending on several factors, such as patient selection, endoscopist's skills, and the difficulties involved during the procedure. This review discusses post-ERCP complications and management strategies with new and evolving concepts.
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Affiliation(s)
- Kemmian D Johnson
- Department of Internal Medicine, Louisiana State University Health Sciences Center, 1542 Tulane Ave Suite 436, New Orleans, LA, 70112, USA
| | - Abhilash Perisetti
- Department of Gastroenterology and Hepatology, University of Arkansas for Medical Sciences, 4301 W Markham St, Little Rock, AR, 72205, USA
| | - Benjamin Tharian
- Department of Gastroenterology and Hepatology, University of Arkansas for Medical Sciences, 4301 W Markham St, Little Rock, AR, 72205, USA
| | - Ragesh Thandassery
- University of Arkansas for Medical Sciences, 4301 W Markham St, Little Rock, AR, 72205, USA
- VISN-16 MD Lead for Advanced Liver Disease, CAVHS, Little Rock, USA
| | - Priya Jamidar
- Yale University School of Medicine, 333 Cedar Street-1080 LMP, P.O. Box 208019, New Haven, CT, 06520, USA
| | - Hemant Goyal
- Department of Internal Medicine, The Wright Center for Graduate Medical Education, 111 North Washington Avenue, Scranton, PA, 18503, USA.
| | - Sumant Inamdar
- Department of Gastroenterology and Hepatology, University of Arkansas for Medical Sciences, 4301 W Markham St, Little Rock, AR, 72205, USA
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Does melatonin addition to indomethacin decrease post endoscopic retrograde cholangiopancreatography pancreatitis? A randomized double-blind controlled trial. Eur J Gastroenterol Hepatol 2019; 31:1350-1355. [PMID: 31524774 DOI: 10.1097/meg.0000000000001531] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
OBJECTIVE Post-ERCP pancreatitis (PEP) is the most prevalent complication of endoscopic retrograde cholangiopancreatography (ERCP). Melatonin has been mentioned as a protective factor against acute pancreatitis. The present study was conducted to determine whether melatonin addition to indomethacin reduces the rate of PEP occurrence. METHODS A double-blind randomized clinical trial was conducted on 411 patients undergoing ERCP. Baseline blood samples were collected, and the patients were given melatonin 3 mg tablets plus indomethacin suppository 100 mg or placebo plus indomethacin suppository 100 mg, 1 h before ERCP. The occurrence of PEP was the primary outcome. The concentrations of amylase and lipase were also measured 24 h after ERCP. RESULTS Demographic characteristics of patients, characteristics of ERCP procedures, and baseline levels of amylase and lipase were found to be similar in both groups. The overall rate of PEP was equal to 9.5% in intention-to-treat (ITT) and 11.4% in per-protocol (PP) analyses. There was a significant difference in the rate of PEP between the melatonin and placebo groups (8.7% vs. 11.4% in ITT and 9.3% vs. 13.6% in PP, respectively). In addition, after 24 h, amylase and lipase levels were lower in the melatonin group than in the placebo group (P = 0.041 and 0.032, respectively). CONCLUSION The results of the present study showed that, administration of melatonin 3 mg tablets plus indomethacin suppository 100 mg 1 h before ERCP could decrease the PEP rate and amylase and lipase levels compared to administration of indomethacin suppository 100 mg alone.
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Chetcuti Zammit S, Sanders DS, Sidhu R. Can indomethacin be helpful in double balloon enteroscopy-assisted procedures? Endosc Int Open 2019; 7:E730-E731. [PMID: 31080877 PMCID: PMC6509041 DOI: 10.1055/a-0842-6496] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/18/2022] Open
Affiliation(s)
- Stefania Chetcuti Zammit
- Academic Department of Gastroenterology, Royal Hallamshire Hospital, Sheffield Teaching Hospitals, Sheffield, UK,Corresponding author Stefania Chetcuti Zammit Sheffield Teaching Hospitals NHS Foundation Trust – GastroenterologyGlossop Road Sheffield S10 2JFUnited Kingdom of Great Britain and Northern Ireland+01142712692
| | - David S. Sanders
- Academic Department of Gastroenterology, Royal Hallamshire Hospital, Sheffield Teaching Hospitals, Sheffield, UK
| | - Reena Sidhu
- Academic Department of Gastroenterology, Royal Hallamshire Hospital, Sheffield Teaching Hospitals, Sheffield, UK
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Lai JH, Hung CY, Chu CH, Chen CJ, Lin HH, Lin HJ, Lin CC. A randomized trial comparing the efficacy of single-dose and double-dose administration of rectal indomethacin in preventing post-endoscopic retrograde cholangiopancreatography pancreatitis. Medicine (Baltimore) 2019; 98:e15742. [PMID: 31096538 PMCID: PMC6531188 DOI: 10.1097/md.0000000000015742] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/23/2023] Open
Abstract
BACKGROUND AND AIMS The before-procedure or after-procedure rectal indomethacin administration was shown to be useful in preventing post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis. We designed this prospective randomized study to compare the efficacy of single-dose and double-dose rectal indomethacin administration in preventing post-ERCP pancreatitis (PEP). METHODS We enrolled patients who underwent the ERCP in Taipei Mackay Memorial Hospital from 2016 June to 2017 November. Patients were randomly assigned to 2 groups: single and double-dose groups. The primary endpoint was the frequency of post-ERCP pancreatitis. RESULTS A total 162 patients participated in this study, and there were 87 patients randomly assigned to the single-dose group, and 75 patients were assigned to the double-dose group. In the high-risk patients, the incidence of PEP was lower in double-dose patients (4.8%) than the single-dose patients (9.5%), but there was no significant difference (P =.24). Difficult cannulation was the only 1 risk factor for PEP after rectal indomethacin treatment. CONCLUSIONS Single-dose rectal indomethacin administration immediately after ERCP in general population is good enough to prevent PEP, but difficult cannulation could induce the PEP frequency up to 15.4% even under rectal indomethacin use.
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Abstract
PURPOSE OF REVIEW Endoscopic retrograde cholangiopancreatography (ERCP) is a commonly performed procedure to manage pancreaticobiliary disease. Post-ERCP pancreatitis (PEP) is the most common adverse event of ERCP with a significant burden of morbidity and cost. RECENT FINDINGS Appropriate indication and counseling is mandatory especially for patients at increased risk for PEP such as those with suspected sphincter of Oddi dysfunction, pancreatic indications, and a prior history of PEP. Guidewire-facilitated deep cannulation is favored over contrast injection. High-quality trials support the use of rectal administered non-steroidal anti-inflammatory agents and pancreatic duct stent placement for high-risk patients. There is emerging evidence favoring the use of rectal NSAIDs and aggressive hydration in average-risk patients though further studies are required. There is also growing interest in the use of combination therapies as well such as pancreatic stents in combination with NSAIDs. The initial step towards PEP prevention involves careful patient selection and informed decision-making. Endoscopists should use several approaches to mitigate the risk of PEP, including guidewire-assisted cannulation, pancreatic stent placement, and rectal NSAIDs use for high-risk patients. The exact role of aggressive hydration and combination therapies needs to be further investigated.
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Affiliation(s)
- Han Zhang
- Department of Medicine, Division of Gastroenterology, Keck School of Medicine, University of Southern California, D & T Building Room B4H100, 1983 Marengo St, Los Angeles, CA, 90033-1370, USA
| | - Jaehoon Cho
- Department of Medicine, Division of Gastroenterology, Keck School of Medicine, University of Southern California, D & T Building Room B4H100, 1983 Marengo St, Los Angeles, CA, 90033-1370, USA
| | - James Buxbaum
- Department of Medicine, Division of Gastroenterology, Keck School of Medicine, University of Southern California, D & T Building Room B4H100, 1983 Marengo St, Los Angeles, CA, 90033-1370, USA.
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Sheiybani G, Brydon P, Toolan M, Linehan J, Farrant M, Colleypriest B. Does rectal diclofenac reduce post-ERCP pancreatitis? A district general hospital experience. Frontline Gastroenterol 2018; 9:73-77. [PMID: 29484164 PMCID: PMC5824769 DOI: 10.1136/flgastro-2017-100832] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/03/2017] [Revised: 06/08/2017] [Accepted: 07/03/2017] [Indexed: 02/04/2023] Open
Abstract
INTRODUCTION There is controversy in the literature recently regarding the efficacy of rectal non-steroidal anti-inflammatory drugs (NSAID) to prevent post-ERCP pancreatitis (PEP). The aim of this study was to compare the incidence of PEP in three distinct groups of patients at the Royal United Hospital, Bath: no use of rectal diclofenac, selective use and blanket use without contraindication. METHOD Readmission data, blood results, radiology reports and discharge summaries were used to identify patients with PEP from August 2010 to December 2015. The administration of rectal diclofenac postprocedure was recorded from the endoscopy reporting system. RESULTS 1318 endoscopic retrograde cholangiopancreatographies (ERCP) were performed by four endoscopists during the study period with 66 (5.0%) cases of pancreatitis. 445 ERCPs were performed prior to the introduction of NSAID use during which time, with an incidence of 35 (7.9%) episodes of PEP. During the selective period of NSAID use (high-risk patients) 539 ERCPs were performed and 72 (13.4%) patients received NSAIDs. 17 (3.2%) developed PEP. 334 ERCPs were performed when NSAIDs were given to all patients without contraindication. 289 (86.5%) of patients received rectal diclofenac and 13 (3.9%) developed pancreatitis. There is a statistically significant decrease in PEP comparing the groups of patients receiving NSAIDs selectively (p=0.0009) or routinely (p=0.0172) when compared with none. There is no difference between the selective and routine group (p=0.571). CONCLUSION Our data demonstrate that the introduction of a selective or routine use of NSAIDs for PEP in a District General Hospital (DGH) significantly decreases the risk of pancreatitis (risk reduction 43.7%).
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Affiliation(s)
| | - Peter Brydon
- Gastroenterology, Royal United Hospital, Bath, UK
| | | | - John Linehan
- Gastroenterology, Royal United Hospital, Bath, UK
| | - Mark Farrant
- Gastroenterology, Royal United Hospital, Bath, UK
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