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Zhang X, Zhang JM, Wei W, Lin H. Nitroglycerin combined with NSAIDs for prevention of post-ERCP pancreatitis: A meta-analysis of prospective, randomized, controlled trials. Medicine (Baltimore) 2024; 103:e38764. [PMID: 38968498 PMCID: PMC11224882 DOI: 10.1097/md.0000000000038764] [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: 07/22/2023] [Accepted: 06/10/2024] [Indexed: 07/07/2024] Open
Abstract
BACKGROUND Acute pancreatitis is the most common complication of endoscopic retrograde cholangiopancreatography (ERCP), with an incidence of approximately 9.7% according to some literature reviews. Recent clinical guidelines propose that glyceryl trinitrate (GTN) can reduce the incidence of post-ERCP pancreatitis (PEP). However, currently, no guidelines provide an exact opinion on GTN and nonsteroidal anti-inflammatory drugs (NSAIDs) to prevent post-ERCP pancreatitis. OBJECTIVE A meta-analysis was performed of published, full-length, randomized controlled trials (RCTs) evaluating the effects of prophylactic use of GTN, including GTN alone or GTN in combination with NSAIDs, on the prevention of PEP. METHODS Literature searches were conducted using PubMed, Embase, Web of Science, and The Cochrane Library. Search terms included "endoscopic retrograde cholangiopancreatography" OR "ERCP," "OR 'PEP' OR 'post-endoscopic retrograde cholangiopancreatography pancreatitis', pancreatitis," "GTN" OR "glyceryl trinitrate" OR "nitroglycerin," "NSAIDs" OR "Nonsteroidal Anti-inflammatory Drugs" and limited to RCT. RESULTS A total of 10 RCTs comprising 3240 patients undergoing ERCP were included. Meta-analysis revealed that the administration of GTN was associated with a significant reduction in the overall incidence of PEP. Moreover, PEP incidence was significantly lower in the GTN combined with the NSAIDs group than in the GTN alone group. GTN alone or GTN combined with NSAIDs may not reduce the severity of PEP (risk ratio = 0.64; 95% confidence interval: 0.41-0.99; P = .04). The difference in incidence between the 2 groups is 1.01% (6/594) in the GTN with NSAIDs group and 2.36% (14/592) in the placebo group. CONCLUSION GTN has a significant benefit in preventing postoperative ERCP pancreatitis (P < .001). And neither GTN nor GTN plus NSAIDs reduces the incidence of non-mild ERCP postoperative pancreatitis. These conclusions need to be confirmed by high-quality randomized controlled studies with multicenter, large samples, and long-term follow-up.
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Affiliation(s)
- Xuan Zhang
- Fuzhou First General Hospital Affiliated with Fujian Medical University, China
| | - Jing-Ming Zhang
- Fuzhou First General Hospital Affiliated with Fujian Medical University, China
| | - Wan Wei
- The Affiliated Huai’an No. 1 People’s Hospital of Nanjing Medical University, Huaian, China
| | - Hui Lin
- Fuzhou First General Hospital Affiliated with Fujian Medical University, China
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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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Akshintala VS, Kanthasamy K, Bhullar FA, Sperna Weiland CJ, Kamal A, Kochar B, Gurakar M, Ngamruengphong S, Kumbhari V, Brewer-Gutierrez OI, Kalloo AN, Khashab MA, van Geenen EJM, Singh VK. Incidence, severity, and mortality of post-ERCP pancreatitis: an updated systematic review and meta-analysis of 145 randomized controlled trials. Gastrointest Endosc 2023; 98:1-6.e12. [PMID: 37004815 DOI: 10.1016/j.gie.2023.03.023] [Citation(s) in RCA: 40] [Impact Index Per Article: 20.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/04/2021] [Revised: 03/01/2023] [Accepted: 03/21/2023] [Indexed: 04/04/2023]
Abstract
BACKGROUND AND AIMS The incidence, severity, and mortality of post-ERCP pancreatitis (PEP) largely remain unknown with changing trends in ERCP use, indication, and techniques. We sought to determine the incidence, severity, and mortality of PEP in consecutive and high-risk patients based on a systemic review and meta-analysis of patients in placebo and no-stent arms of randomized control trials (RCTs). METHODS The MEDLINE, Embase, and Cochrane databases were searched from the inception of each database to June 2022 to identify full-text RCTs evaluating PEP prophylaxes. The incidence, severity, and mortality of PEP from the placebo or no-stent arms of RCTs were recorded for consecutive and high-risk patients. A random-effects meta-analysis for a proportions model was used to calculate PEP incidence, severity, and mortality. RESULTS One hundred forty-five RCTs were found with 19,038 patients in the placebo or no-stent arms. The overall cumulative incidence of PEP was 10.2% (95% confidence interval [CI], 9.3-11.3), predominantly among the academic centers conducting such RCTs. The cumulative incidences of severe PEP and mortality were .5% (95% CI, .3-.7) and .2% (95% CI, .08-.3), respectively, across 91 RCTs with 14,441 patients. The cumulative incidences of PEP and severe PEP were 14.1% (95% CI, 11.5-17.2) and .8% (95% CI, .4-1.6), respectively, with a mortality rate of .2% (95% CI, 0-.3) across 35 RCTs with 3733 patients at high risk of PEP. The overall trend for the incidence of PEP among patients randomized to placebo or no-stent arms of RCTs has remained unchanged from 1977 to 2022 (P = .48). CONCLUSIONS The overall incidence of PEP is 10.2% but is 14.1% among high-risk patients based on this systematic review of placebo or no-stent arms of 145 RCTs; this rate has not changed between 1977 and 2022. Severe PEP and mortality from PEP are relatively uncommon.
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Affiliation(s)
- Venkata S Akshintala
- Division of Gastroenterology, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA
| | - Kavin Kanthasamy
- Division of Gastroenterology, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA
| | - Furqan A Bhullar
- Division of Gastroenterology, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA
| | | | - Ayesha Kamal
- Division of Gastroenterology, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA
| | - Bharati Kochar
- Division of Gastroenterology, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Merve Gurakar
- Division of Gastroenterology, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA
| | | | - Vivek Kumbhari
- Division of Gastroenterology, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA
| | | | - Anthony N Kalloo
- Division of Gastroenterology, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA
| | - Mouen A Khashab
- Division of Gastroenterology, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA
| | - Erwin-Jan 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, Maryland, USA
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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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Obeidat AE, Mahfouz R, Monti G, Kozai L, Darweesh M, Mansour MM, Alqam A, Hernandez D. Post-Endoscopic Retrograde Cholangiopancreatography Pancreatitis: What We Already Know. Cureus 2022; 14:e21773. [PMID: 35251843 PMCID: PMC8890589 DOI: 10.7759/cureus.21773] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/31/2022] [Indexed: 11/05/2022] Open
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Dar HA, Shah A, Javid G, Khan MA, Singh B, Sheikh NA, Ashraf A, Mohammad S. Randomized trial of high-dose rectal diclofenac suppository and epinephrine spray on duodenal papilla for prevention of post-endoscopic retrograde cholangiopancreatography pancreatitis. Indian J Gastroenterol 2021; 40:483-491. [PMID: 34767149 DOI: 10.1007/s12664-021-01161-z] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/17/2020] [Accepted: 02/22/2021] [Indexed: 02/08/2023]
Abstract
BACKGROUND AND AIMS High-dose rectal diclofenac suppository and epinephrine spray on duodenal papilla during endoscopic retrograde cholangiopancreatography (ERCP) may reduce the incidence of post-ERCP pancreatitis. We performed randomized trial to compare the effect of combination of rectal diclofenac and epinephrine spray on papilla (group A) vs. combination of rectal diclofenac with saline spray (group B) for prevention of post-ERCP pancreatitis. METHODS We performed a double-blind trial at tertiary care center from April 2018 to May 2020 on 882 patients with naive papilla undergoing ERCP. The patients were randomly assigned to groups, A (n=437) or B (n=445). All patients received a single dose of rectal diclofenac 100 mg within 30 minutes before ERCP; 20 mL of diluted epinephrine 0.02% (group A) or saline (group B) was then sprayed on the duodenal papilla at the end of ERCP. The primary outcome was to compare incidence of post-ERCP pancreatitis (PEP) in two groups. RESULTS The groups had similar baseline characteristics. PEP developed in 28 patients in group A (6.4%) and 35 patients in group B (7.9%) (relative risk, 1.1; 95% CI, 0.87-1.39; p=0.401). CONCLUSION Our study showed that addition of epinephrine spray on duodenal papilla did not reduce the risk of post-ERCP pancreatitis. There is need for further studies to evaluate the role of different concentrations of epinephrine spray on papilla for prevention of post-ERCP pancreatitis. TRIAL REGISTRATION Clinical Trials Registry- India (CTRI/2018/04/013396).
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Affiliation(s)
- Hilal Ahmad Dar
- Department of Gastroenterology, Sher- i- Kashmir Institute of Medical Sciences, Srinagar, Kashmir, 190 011, India. .,Department of Internal Medicine, Government Medical College, Baramulla, Kashmir, 193 101, India.
| | - Altaf Shah
- Department of Gastroenterology, Sher- i- Kashmir Institute of Medical Sciences, Srinagar, Kashmir, 190 011, India
| | - Gul Javid
- Department of Gastroenterology, Sher- i- Kashmir Institute of Medical Sciences, Srinagar, Kashmir, 190 011, India
| | - Mushtaq Ahmad Khan
- Department of Gastroenterology, Sher- i- Kashmir Institute of Medical Sciences, Srinagar, Kashmir, 190 011, India
| | - Bhagat Singh
- Department of Gastroenterology, Sher- i- Kashmir Institute of Medical Sciences, Srinagar, Kashmir, 190 011, India
| | - Nadeem Ahmad Sheikh
- Department of Gastroenterology, Sher- i- Kashmir Institute of Medical Sciences, Srinagar, Kashmir, 190 011, India
| | - Aadil Ashraf
- Department of Gastroenterology, Sher- i- Kashmir Institute of Medical Sciences, Srinagar, Kashmir, 190 011, India
| | - Sozia Mohammad
- Department of Microbiology, Sher- i- Kashmir Institute of Medical Sciences, Srinagar, Kashmir, 190 011, India
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Lyu Y, Wang B, Cheng Y, Xu Y, Du W. Comparative Efficacy of 9 Major Drugs for Postendoscopic Retrograde Cholangiopancreatography Pancreatitis: A Network Meta-Analysis. Surg Laparosc Endosc Percutan Tech 2019; 29:426-432. [PMID: 31490455 DOI: 10.1097/sle.0000000000000707] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND Postendoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) is one of the most common complications after ERCP. The optimal drugs for reducing the risk of PEP are still unclear. This study aimed to compare the efficacy of 9 major drugs used worldwide for the prevention of PEP through a network meta-analysis. METHODS We conducted a systematic search of the literature up to October 2018 on PubMed, Embase, Web of Science, the Cochrane Central Library, and ClinicalTrials.gov. Randomized controlled trials (RCTs) comparing allopurinol, diclofenac, gabexate (GAB), glyceryl trinitrate (GTN), indomethacin, nafamostat, octreotide, somatostatin, and ulinastatin for protection against PEP were included. RESULTS Eighty-six randomized controlled trials involving 25,246 patients were included in this network meta-analysis. Results indicated that diclofenac, GAB, GTN, indomethacin, somatostatin, and ulinastatin were more effective than placebo with odds ratios ranging between 0.48 (95% credible interval, 0.26-0.86) for GAB and 0.61 (0.39-0.94) for somatostatin. However, allopurinol, nafamostat, and octreotide showed similar efficacy as placebo in reducing the risk of PEP. No significant differences were found in the efficacy between diclofenac, GAB, GTN, indomethacin, somatostatin, and ulinastatin. In terms of prognosis, GAB may be the most effective treatment (surface under the cumulative ranking curve=70.6%) and the least effective was octreotide (surface under the cumulative ranking curve=28%). CONCLUSIONS Although our analysis suggests that GAB may be the most effective drug in preventing PEP, the limitations of our study warrants more high-quality head-to-head trials of these clinical drugs in the future.
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Affiliation(s)
- Yunxiao Lyu
- Department of Hepatobiliary Surgery, Dongyang People's Hospital, Dongyang, Zhejiang, China
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Lyu Y, Cheng Y, Wang B, Xu Y, Du W. What is impact of nonsteroidal anti-inflammatory drugs in the prevention of post-endoscopic retrograde cholangiopancreatography pancreatitis: a meta-analysis of randomized controlled trials. BMC Gastroenterol 2018; 18:106. [PMID: 29973142 PMCID: PMC6032784 DOI: 10.1186/s12876-018-0837-4] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/20/2017] [Accepted: 06/26/2018] [Indexed: 12/16/2022] Open
Abstract
Background Recently, although studies have investigated the role of NSAIDs in the prevention of post-endoscopic retrograde cholangiopancreatography pancreatitis (PEP), selection of the ideal drug, the time and route of its administration for the appropriate population remain controversial. Methods A systematic search was done in sources including PubMed, Embase, Web of Science, the Cochrane Library Central, and ClinicalTrials.gov from from August 1, 1990 to August 1, 2017. Randomized controlled trials comparing the prophylactic use of NSAIDs versus a placebo were included. Statistical analysis was performed using the RevMan 5.3 software to assess the outcomes. Results A total of 21 randomized controlled trials were included in the meta-analysis. Our study showed that NSAIDs significantly reduced the incidence of PEP (RR, 0.61, 95%CI,0.52–0.72; p < 0.00001). The analysis showed that indomethacin administration post-ERCP (RR, 0.47; 95% CI, 0.31–0.70; p = 0.0002) appeared to be more effective in preventing PEP than indomethacin administration pre-ERCP (RR, 0.59; 95% CI, 0.45–0.79; P = 0.0003), but there was no significant difference between the high-risk and average-risk population(p = 0.13). In the diclofenac group, it was noted that administration of diclofenac pre-ERCP (RR, 0.32; 95% CI, 0.16–0.63; p = 0.001) was more effective than that in post-ERCP (RR, 0.65; 95% CI, 0.27–1.599; p = 0.35). The relative risk of PEP was 0.63 (95% CI, 0.27–1.50; p = 0.30) in high-risk patients and 0.41 (95% CI, 0.17–0.98; p = 0.02) in average-risk patients. With regard to the route of administration, PEP decreased significantly only in patients receiving the drug rectally (RR, 0.53; 95% CI, 0.44–0.63; p < 0.00001), but not for those who received intramuscularly (RR, 0.74; 95% CI, 0.47–1.17; p = 0.20), intravenously (RR, 0.97; 95% CI, 0.51–1.83; p = 0.93), and orally (RR = 0.88; 95% CI, 0.55–0.1.43; p = 0.62). Conclusions Rectal administration of NSAIDs (both indomethacin and diclofenac) was effective in preventing PEP in unselected patients. A single dose of indomethacin after ERCP might be effective in preventing PEP in both high-risk and average-risk patients. However, diclofenac administered rectally before ERCP might be protective against PEP in high-risk patients compared to a placebo. However, more high quality head-to-head RCTs are required.
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Affiliation(s)
- Yunxiao Lyu
- Department of General Surgery, Dongyang people's Hospital, Dongyang, 322100, Zhejiang Province, China.
| | - Yunxiao Cheng
- Department of General Surgery, Dongyang people's Hospital, Dongyang, 322100, Zhejiang Province, China
| | - Bin Wang
- Department of General Surgery, Dongyang people's Hospital, Dongyang, 322100, Zhejiang Province, China
| | - Yueming Xu
- Department of General Surgery, Dongyang people's Hospital, Dongyang, 322100, Zhejiang Province, China
| | - Weibing Du
- Department of General Surgery, Dongyang people's Hospital, Dongyang, 322100, Zhejiang Province, China
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Parekh PJ, Majithia R, Sikka SK, Baron TH. The "Scope" of Post-ERCP Pancreatitis. Mayo Clin Proc 2017; 92:434-448. [PMID: 28160947 DOI: 10.1016/j.mayocp.2016.10.028] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/01/2016] [Revised: 10/22/2016] [Accepted: 10/31/2016] [Indexed: 12/14/2022]
Abstract
Pancreatitis is the most common adverse event of endoscopic retrograde cholangiopancreatography, with the potential for clinically significant morbidity and mortality. Several patient and procedural risk factors have been identified that increase the risk of post-endoscopic retrograde cholangiopancreatography pancreatitis (PEP). Considerable research efforts have identified several pharmacologic and procedural interventions that can drastically affect the incidence of PEP. This review article addresses the underlying mechanisms at play for the development of PEP, identifying patient and procedural risk factors and meaningful use of risk-stratification information, and details current interventions aimed at reducing the risk of this complication.
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Affiliation(s)
- Parth J Parekh
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Tulane University, New Orleans, LA
| | - Raj Majithia
- Division of Gastroenterology and Hepatology, University of North Carolina-Johnston Healthcare, Smithfield
| | - Sanjay K Sikka
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Tulane University, New Orleans, LA
| | - Todd H Baron
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, University of North Carolina, Chapel Hill.
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Katsinelos P, Lazaraki G, Chatzimavroudis G, Katsinelos T, Georgakis N, Anastasiadou K, Gatopoulou A, Zeglinas C, Psarras K, Kountouras J. Impact of nitroglycerin and glucagon administration on selective common bile duct cannulation and prevention of post-ERCP pancreatitis. Scand J Gastroenterol 2017; 52:50-55. [PMID: 27690682 DOI: 10.1080/00365521.2016.1228117] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
OBJECTIVE Easy common bile duct (CBD) cannulation is associated with low complication rate. This study aimed to investigate the potential impact of nitroglycerin and glucagon administration on selective CBD cannulation and prevention of post-ERCP pancreatitis. METHODS A prospective single center, double-blind randomized study in which a total of 455 patients were randomly assigned to CBD cannulation by receiving 6 puffs (2.4 mg) sublingual nitroglycerin and glucagon 1 mg intravenously (n = 227, group A) or 6 puffs sterile water and 20 mg hyoscine-n-butyl bromide intravenously (n = 228, group B). After ERCP, patients were followed for the development of drugs' side-effects and post-ERCP complications. RESULTS There were no statistically significant differences between the two groups regarding demographic data and ERCP findings. Success rate of selective CΒD cannulation was 95.15% in group A versus 82.29% in group B (p < .001). Time required for CBD cannulation was 2.82 ± 2.31 min in group A versus 4.27 ± 3.84 min in group B (p = .021). Needle-knife papillotomy was used in 11 (4.85%) patients of group A and 39 (17.11%) patients of group B (p = .001). The frequency of post-ERCP pancreatitis was significantly lower in group A than in group B (3.08% versus 7.46%, p = .037). No difference was observed between the two groups with regard to the occurrence of post-procedure hemorrhage. There was no procedure-related mortality; no adverse event related to the combination regimen was observed. CONCLUSIONS Combined nitroglycerin and glucagon administration achieves a high selective CBC cannulation rates with concomitant reduction of post-ERCP pancreatitis incidence. However, further relative large-scale studies are needed to confirm our findings before definite conclusions can be drawn (Clinical trial registration number: NT: 4321).
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Affiliation(s)
- Panagiotis Katsinelos
- a Division of Gastroenterology, Second Department of Internal Medicine , Ippokration Hospital, Medical School of Aristotle University , Thessaloniki , Greece.,b Second Department of Internal Medicine , Ippokration Hospital, Medical School of Aristotle University , Thessaloniki , Greece
| | - Georgia Lazaraki
- a Division of Gastroenterology, Second Department of Internal Medicine , Ippokration Hospital, Medical School of Aristotle University , Thessaloniki , Greece
| | - Grigoris Chatzimavroudis
- a Division of Gastroenterology, Second Department of Internal Medicine , Ippokration Hospital, Medical School of Aristotle University , Thessaloniki , Greece
| | - Taxiarchis Katsinelos
- c Department of Pharmacology , Medical School of Aristotle University , Thessaloniki , Greece
| | - Nikos Georgakis
- a Division of Gastroenterology, Second Department of Internal Medicine , Ippokration Hospital, Medical School of Aristotle University , Thessaloniki , Greece.,b Second Department of Internal Medicine , Ippokration Hospital, Medical School of Aristotle University , Thessaloniki , Greece
| | - Kyriaki Anastasiadou
- a Division of Gastroenterology, Second Department of Internal Medicine , Ippokration Hospital, Medical School of Aristotle University , Thessaloniki , Greece.,b Second Department of Internal Medicine , Ippokration Hospital, Medical School of Aristotle University , Thessaloniki , Greece
| | - Anthi Gatopoulou
- a Division of Gastroenterology, Second Department of Internal Medicine , Ippokration Hospital, Medical School of Aristotle University , Thessaloniki , Greece
| | - Christos Zeglinas
- a Division of Gastroenterology, Second Department of Internal Medicine , Ippokration Hospital, Medical School of Aristotle University , Thessaloniki , Greece
| | - Kyriakos Psarras
- b Second Department of Internal Medicine , Ippokration Hospital, Medical School of Aristotle University , Thessaloniki , Greece
| | - Jannis Kountouras
- a Division of Gastroenterology, Second Department of Internal Medicine , Ippokration Hospital, Medical School of Aristotle University , Thessaloniki , Greece.,b Second Department of Internal Medicine , Ippokration Hospital, Medical School of Aristotle University , Thessaloniki , Greece
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Endoscopic and pharmacological treatment for prophylaxis against postendoscopic retrograde cholangiopancreatography pancreatitis: a meta-analysis and systematic review. Eur J Gastroenterol Hepatol 2016; 28:1415-1424. [PMID: 27580214 DOI: 10.1097/meg.0000000000000734] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
BACKGROUND AND AIM Postendoscopic retrograde cholangiopancreatography (post-ERCP) pancreatitis (PEP) is the most common complication following ERCP. We carried out a systematic review and meta-analysis of the global literature on PEP prevention to provide clinical guidance and a framework for future research in this important field. METHODS PubMed, Embase, Science Citation Index, Ovid, and the Cochrane Controlled Trials Register were searched by two independent reviewers to identify full-length, prospective, randomized controlled trials (RCTs) published up until March 2016 investigating the use of pancreatic duct stents and pharmacological agents to prevent PEP. RESULTS Twelve RCTs comparing the risk of PEP after pancreatic duct stent placement (1369 patients) and 30 RCTs comparing pharmacological agents over placebo (10251 patients) fulfilled the inclusion criteria and were selected for final review and analysis. Meta-analysis showed that prophylactic pancreatic stents significantly decreased the odds of post-ERCP pancreatitis [odds ratio (OR), 0.28; 95% confidence interval (CI), 0.18-0.42]. Significant OR reduction of PEP was also observed in relation to rectal administration of diclofenac (OR, 0.24; 95% CI, 0.12-0.48) and rectal administration of indometacin (OR, 0.59; 95% CI, 0.44-0.79) compared with placebo. Subgroup analysis showed a significant reduction with bolus-administered somatostatin (OR, 0.23; 95% CI, 0.11-0.49). Subgroup analysis showed a significant reduction with bolus-administered somatostatin (OR, 0.23; 95% CI, 0.11-0.49). CONCLUSION Pancreatic stent placement, rectal diclofenac, and bolus administration of somatostatin appear to be most effective in preventing post-ERCP pancreatitis.
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12
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Wang AY, Strand DS, Shami VM. Prevention of Post-Endoscopic Retrograde Cholangiopancreatography Pancreatitis: Medications and Techniques. Clin Gastroenterol Hepatol 2016; 14:1521-1532.e3. [PMID: 27237430 DOI: 10.1016/j.cgh.2016.05.026] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/02/2014] [Revised: 05/17/2016] [Accepted: 05/18/2016] [Indexed: 02/07/2023]
Abstract
Over the past 2 decades, it increasingly has been recognized that endoscopic retrograde cholangiopancreatography (ERCP) is the most predictable provocateur of acute pancreatitis, with an incidence of more than 15% in high-risk patients. For this reason, there has been considerable interest in the effect of periprocedural drug administration as well as different ERCP techniques on both the incidence and severity of post-ERCP pancreatitis. Although many agents and techniques have shown promise in small clinical studies, the majority of these have failed to yield consistent benefit in larger randomized patient groups. This review summarizes the data on medications and ERCP techniques that have been studied for the prevention of post-ERCP pancreatitis.
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Affiliation(s)
- Andrew Y Wang
- Division of Gastroenterology and Hepatology, University of Virginia Health System, Charlottesville, Virginia.
| | - Daniel S Strand
- Division of Gastroenterology and Hepatology, University of Virginia Health System, Charlottesville, Virginia
| | - Vanessa M Shami
- Division of Gastroenterology and Hepatology, University of Virginia Health System, Charlottesville, Virginia
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13
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Kubiliun NM, Adams MA, Akshintala VS, Conte ML, Cote GA, Cotton PB, Dumonceau JM, Elta GH, Fogel EL, Freeman ML, Lehman GA, Naveed M, Romagnuolo J, Scheiman JM, Sherman S, Singh VK, Elmunzer BJ. Evaluation of Pharmacologic Prevention of Pancreatitis After Endoscopic Retrograde Cholangiopancreatography: A Systematic Review. Clin Gastroenterol Hepatol 2015; 13:1231-9; quiz e70-1. [PMID: 25579870 DOI: 10.1016/j.cgh.2014.11.038] [Citation(s) in RCA: 63] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/03/2014] [Revised: 11/19/2014] [Accepted: 11/20/2014] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS There is controversy over the efficacy of pharmacologic agents for preventing pancreatitis after endoscopic retrograde cholangiopancreatography (PEP). We performed a systematic review of PEP pharmacoprevention to evaluate safety and efficacy. METHODS We performed a systematic search of the literature for randomized controlled trials (RCTs) and meta-analyses of PEP pharmacoprevention through February 2014. After identifying relevant studies, 2 reviewers each extracted information on study characteristics, clinical outcomes, and risk of bias. A research classification scale was developed to identify pharmacologic agents ready for clinical use, agents for which a confirmatory RCT should be considered a high priority, agents for which exploratory studies are still necessary, and agents for which additional research should be of low priority. Clinical and research recommendations for each agent were made by consensus after considering research classification results and other important factors such as magnitude of benefit, safety, availability, and cost. RESULTS After screening 851 citations and 263 potentially relevant articles, 2 reviewers identified 85 RCTs and 28 meta-analyses that were eligible. On the basis of these studies, rectal nonsteroidal anti-inflammatory drugs were found to be appropriate for clinical use, especially for high-risk cases. Sublingual nitroglycerin, bolus-administered somatostatin, and nafamostat were found to be promising agents for which confirmatory research is warranted. Additional research was found to be required to justify confirmatory RCTs for topical epinephrine, aggressive intravenous fluids, gabexate, ulinastatin, secretin, and antibiotics. CONCLUSIONS On the basis of a systematic review, NSAIDs are appropriate for use in prevention of PEP, especially for high-risk cases. Additional research is necessary to clarify the role of other pharmacologic agents. These findings could inform future research and guide clinical decision-making and policy.
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Affiliation(s)
- Nisa M Kubiliun
- Division of Digestive and Liver Diseases, University of Texas Southwestern, Dallas, Texas
| | - Megan A Adams
- Division of Gastroenterology, University of Michigan Medical Center, Ann Arbor, Michigan
| | - Venkata S Akshintala
- Division of Gastroenterology, Johns Hopkins Medical Institutions, Baltimore, Maryland
| | - Marisa L Conte
- Taubman Health Sciences Library, University of Michigan, Ann Arbor, Michigan
| | - Gregory A Cote
- Division of Gastroenterology, Indiana University Medical Center, Indianapolis, Indiana; Division of Gastroenterology and Hepatology, Medical University of South Carolina, Charleston, South Carolina
| | - Peter B Cotton
- Division of Gastroenterology and Hepatology, Medical University of South Carolina, Charleston, South Carolina
| | | | - Grace H Elta
- Division of Gastroenterology, University of Michigan Medical Center, Ann Arbor, Michigan
| | - Evan L Fogel
- Division of Gastroenterology, Indiana University Medical Center, Indianapolis, Indiana
| | - Martin L Freeman
- Division of Gastroenterology, University of Minnesota, Minneapolis, Minnesota
| | - Glen A Lehman
- Division of Gastroenterology, Indiana University Medical Center, Indianapolis, Indiana
| | - Mariam Naveed
- Division of Digestive and Liver Diseases, University of Texas Southwestern, Dallas, Texas
| | - Joseph Romagnuolo
- Division of Gastroenterology and Hepatology, Medical University of South Carolina, Charleston, South Carolina
| | - James M Scheiman
- Division of Gastroenterology, University of Michigan Medical Center, Ann Arbor, Michigan
| | - Stuart Sherman
- Division of Gastroenterology, Indiana University Medical Center, Indianapolis, Indiana
| | - Vikesh K Singh
- Division of Gastroenterology, Johns Hopkins Medical Institutions, Baltimore, Maryland
| | - B Joseph Elmunzer
- Division of Gastroenterology, University of Michigan Medical Center, Ann Arbor, Michigan; Division of Gastroenterology and Hepatology, Medical University of South Carolina, Charleston, South Carolina.
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Incidence, severity, and mortality of post-ERCP pancreatitis: a systematic review by using randomized, controlled trials. Gastrointest Endosc 2015; 81:143-149.e9. [PMID: 25088919 DOI: 10.1016/j.gie.2014.06.045] [Citation(s) in RCA: 321] [Impact Index Per Article: 32.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/26/2013] [Accepted: 06/26/2014] [Indexed: 12/14/2022]
Abstract
BACKGROUND Data regarding the incidence and severity of post-ERCP pancreatitis (PEP) are primarily from nonrandomized studies. OBJECTIVE To determine the incidence, severity, and mortality of PEP from a systematic review of the placebo or no-stent arms of randomized, controlled trials (RCTs). DESIGN MEDLINE, EMBASE, and Cochrane databases were searched to identify RCTs evaluating the efficacy of drugs and/or pancreatic stents to prevent PEP. SETTING Systematic review of patients enrolled in RCTs evaluating agents for PEP prophylaxis. PATIENTS Patients in the placebo or no-stent arms of the RCTs INTERVENTION ERCP. MAIN OUTCOME MEASUREMENTS Incidence, severity, and mortality of PEP. RESULTS There were 108 RCTs with 13,296 patients in the placebo or no-stent arms. Overall, the PEP incidence was 9.7% and the mortality rate was 0.7%. Severity of PEP was reported for 8857 patients: 5.7%, 2.6%, and 0.5% of cases were mild, moderate, and severe, respectively. The incidence of PEP in 2345 high-risk patients was 14.7% and the severity of PEP was mild, moderate, and severe in 8.6%, 3.9%, and 0.8%, respectively, with a 0.2% mortality rate. The incidence of PEP was 13% in North American RCTs compared with 8.4% in European and 9.9% in Asian RCTs. ERCPs conducted before and after 2000 had a PEP incidence of 7.7% and 10%, respectively. LIMITATIONS Difference in PEP risk among patients in the included RCTs. CONCLUSION The incidence of PEP and severe PEP is similar in high-risk patients and the overall cohort. Discrepancies in the incidence of PEP across geographic regions require further study.
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Elmunzer BJ. Pharmacologic prevention of pancreatitis after endoscopic retrograde cholangiopancreatography: Present and future. TECHNIQUES IN GASTROINTESTINAL ENDOSCOPY 2014. [DOI: 10.1016/j.tgie.2014.05.003] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
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Abstract
Post-procedure pancreatitis is the most common complication of endoscopic retrograde cholangio pancreatography (ERCP) and carries a high morbidity and mortality occurring in at least 3%-5% of all procedures. We reviewed the available literature searching for "ERCP" and "pancreatitis" and "post-ERCP pancreatitis". in PubMed and Medline. This review looks at the diagnosis, risk factors, causes and methods of preventing post-procedure pancreatitis. These include the evidence for patient selection, endoscopic techniques and pharmacological prophylaxis of ERCP induced pancreatitis. Selecting the right patient for the procedure by a risk benefits assessment is the best way of avoiding unnecessary ERCPs. Risk is particularly high in young women with sphincter of Oddi dysfunction (SOD). Many of the trials reviewed have rather few numbers of subjects and hence difficult to appraise. Meta-analyses have helped screen for promising modalities of prophylaxis. At present, evidence is emerging that pancreatic stenting of patients with SOD and rectally administered nonsteroidal anti-inflammatory drugs in a large unselected trial reduce the risk of post-procedure pancreatitis. A recent meta-analysis have demonstrated that rectally administered indomethecin, just before or after ERCP is associated with significantly lower rate of pancreatitis compared with placebo [OR = 0.49 (0.34-0.71); P = 0.0002]. Number needed to treat was 20. It is likely that one of these prophylactic measures will begin to be increasingly practised in high risk groups.
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Affiliation(s)
- Lin-Lee Wong
- Lin-Lee Wong, Her-Hsin Tsai, Department of Gastroenterology, Castle Hill Hospital, HEY NHS Trust and Hull York Medical School, Cottingham HU165JQ, United Kingdom
| | - Her-Hsin Tsai
- Lin-Lee Wong, Her-Hsin Tsai, Department of Gastroenterology, Castle Hill Hospital, HEY NHS Trust and Hull York Medical School, Cottingham HU165JQ, United Kingdom
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17
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A randomized trial of rectal indomethacin and sublingual nitrates to prevent post-ERCP pancreatitis. Am J Gastroenterol 2014; 109:903-9. [PMID: 24513806 DOI: 10.1038/ajg.2014.9] [Citation(s) in RCA: 42] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/03/2013] [Accepted: 12/06/2013] [Indexed: 12/11/2022]
Abstract
OBJECTIVES Acute pancreatitis is the most common adverse event of endoscopic retrograde cholangiopancreatography (ERCP). Recent data suggest that indomethacin can reduce the risk of post-ERCP pancreatitis (PEP) in high-risk individuals. However, whether the combination of indomethacin and sublingual nitrates is superior to indomethacin alone is unknown. Therefore, we aimed to evaluate the efficacy of rectally administered indomethacin plus sublingual nitrate compared with indomethacin alone to prevent PEP. METHODS During a 17-month period, all eligible patients who underwent ERCP were enrolled in this study. We excluded patients who had undergone a prior endoscopic sphincterotomy. In a double-blind controlled randomized trial, patients received a suppository containing 100 mg of indomethacin, plus 5 mg of sublingual nitrate (group A), or a suppository containing 100 mg of indomethacin, plus sublingual placebo (group B), before ERCP. Serum amylase levels and clinically pertinent evaluations were measured in all patients after ERCP. RESULTS Of the 300 enrolled patients, 150 received indomethacin plus nitrate. Thirty-three patients developed pancreatitis: 10 (6.7%) in group A and 23 (15.3%) in group B (P=0.016, risk ratio=0.39, 95% confidence intervals (CI): 0.18-0.86). More than 80% of the patients were at high risk of developing pancreatitis after ERCP. Absolute risk reduction, relative risk reduction, and number needed to treat for the prevention of PEP were 8.6% (95% CI: 4.7-14.5), 56.2% (95% CI: 50.6-60.8), and 12 (95% CI: 7-22), respectively. CONCLUSIONS Combination of rectal indomethacin and sublingual nitrate given before ERCP was significantly more likely to reduce the incidence of PEP than indomethacin suppository alone. Multicenter trials to confirm these promising findings are needed.
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18
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Arain MA, Freeman ML. Pharmacologic prophylaxis alone is not adequate to prevent post-ERCP pancreatitis. Am J Gastroenterol 2014; 109:910-2. [PMID: 24896759 DOI: 10.1038/ajg.2014.123] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/29/2014] [Accepted: 04/04/2014] [Indexed: 12/11/2022]
Abstract
Post-ERCP pancreatitis (PEP) remains the most common complication following ERCP. Although once considered unpredictable, understanding patient and procedure-related risk factors, and measures such as pancreatic stent placement and pharmacoprophylaxis have been shown to substantially decrease the risk of PEP. In this issue of the Journal, the role of pharmacoprophylaxis is explored in a study comparing rectal indomethacin plus sublingual nitrates vs. rectal indomethacin alone. While showing improved efficacy, dual pharmacoprophylaxis does not appear adequate to obviate the importance of technique-related variables and pancreatic stents. Rather, a comprehensive approach is likely to be the most efficacious strategy to reduce PEP.
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Affiliation(s)
- Mustafa A Arain
- Division of Gastroenterology, Hepatology and Nutrition, University of Minnesota, Minneapolis, Minnesota, USA
| | - Martin L Freeman
- Division of Gastroenterology, Hepatology and Nutrition, University of Minnesota, Minneapolis, Minnesota, USA
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19
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The effect of indomethacin in the prevention of post-endoscopic retrograde cholangiopancreatography pancreatitis: a meta-analysis. Pancreas 2014; 43:338-42. [PMID: 24622061 DOI: 10.1097/mpa.0000000000000086] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
OBJECTIVES Acute pancreatitis after endoscopic retrograde cholangiopancreatography (ERCP) is a severe complication with substantial morbidity and mortality. Indomethacin has been identified to prevent this complication; however, the results using indomethacin have varied. Therefore, we performed a meta-analysis on the efficacy of rectally administered indomethacin in the prevention of post-ERCP pancreatitis (PEP). METHODS A systematic search was performed in November 2012. Randomized, placebo-controlled trials (randomized controlled trials) in adult patients that compared rectally administered indomethacin versus placebo in prevention of PEP were included. Meta-analysis was performed using a fixed-effects model to assess the primary outcome (PEP) and secondary outcomes (mild or moderate to severe PEP) using Review Manager 5.1. RESULTS Four randomized controlled trials met the inclusion criteria (n = 1422). The use of indomethacin near the time of ERCP demonstrated a statistically significant decrease in PEP (odds ratio [OR], 0.49; 95% confidence interval [CI], 0.34-0.71; P < 0.01), mild PEP (OR, 0.52; 95% CI, 0.32-0.86; P = 0.01), and moderate to severe PEP (OR, 0.45; 95% CI, 0.24-0.83; P = 0.01) as compared with placebo. The number needed to treat with indomethacin to prevent 1 episode of pancreatitis is 17 patients. CONCLUSIONS Rectal indomethacin significantly reduced the incidence of PEP. We recommend using indomethacin before or just after the procedure in patients undergoing ERCP.
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20
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Wong LL, Tsai HH. Prevention of post-ERCP pancreatitis. World J Gastrointest Pathophysiol 2014; 5:1-10. [PMID: 24891970 PMCID: PMC4024515 DOI: 10.4291/wjgp.v5.i1.1] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/05/2013] [Revised: 10/26/2013] [Accepted: 01/14/2014] [Indexed: 02/06/2023] Open
Abstract
Post-procedure pancreatitis is the most common complication of endoscopic retrograde cholangio pancreatography (ERCP) and carries a high morbidity and mortality occurring in at least 3%-5% of all procedures. We reviewed the available literature searching for “ERCP” and “pancreatitis” and “post-ERCP pancreatitis”. in PubMed and Medline. This review looks at the diagnosis, risk factors, causes and methods of preventing post-procedure pancreatitis. These include the evidence for patient selection, endoscopic techniques and pharmacological prophylaxis of ERCP induced pancreatitis. Selecting the right patient for the procedure by a risk benefits assessment is the best way of avoiding unnecessary ERCPs. Risk is particularly high in young women with sphincter of Oddi dysfunction (SOD). Many of the trials reviewed have rather few numbers of subjects and hence difficult to appraise. Meta-analyses have helped screen for promising modalities of prophylaxis. At present, evidence is emerging that pancreatic stenting of patients with SOD and rectally administered nonsteroidal anti-inflammatory drugs in a large unselected trial reduce the risk of post-procedure pancreatitis. A recent meta-analysis have demonstrated that rectally administered indomethecin, just before or after ERCP is associated with significantly lower rate of pancreatitis compared with placebo [OR = 0.49 (0.34-0.71); P = 0.0002]. Number needed to treat was 20. It is likely that one of these prophylactic measures will begin to be increasingly practised in high risk groups.
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21
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Kubiliun NM, Elmunzer BJ. Preventing pancreatitis after endoscopic retrograde cholangiopancreatography. Gastrointest Endosc Clin N Am 2013; 23:769-86. [PMID: 24079789 DOI: 10.1016/j.giec.2013.06.003] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
Post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis is a common and potentially devastating complication of ERCP. Advances in risk stratification, patient selection, procedure technique, and prophylactic interventions have substantially improved the endoscopists' ability to prevent this complication. This article presents the evidence-based approaches to preventing post-ERCP pancreatitis and suggests timely research questions in this important area.
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Affiliation(s)
- Nisa M Kubiliun
- Division of Gastroenterology, University of Michigan Medical Center, 3912 Taubman Center, Ann Arbor, MI 48109, USA
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Ding J, Jin X, Pan Y, Liu S, Li Y. Glyceryl trinitrate for prevention of post-ERCP pancreatitis and improve the rate of cannulation: a meta-analysis of prospective, randomized, controlled trials. PLoS One 2013; 8:e75645. [PMID: 24098392 PMCID: PMC3787965 DOI: 10.1371/journal.pone.0075645] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2013] [Accepted: 08/15/2013] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND Acute pancreatitis is the most common complication of diagnostic and therapeutic endoscopic retrograde cholangiopancreatography (ERCP). Several clinical trials used glyceryl trinitrate (GTN) to prevent the incidence of post-ERCP pancreatitis (PEP). However, the results were still controversial. OBJECTIVE To conduct a meta-analysis of published, full-length, randomized controlled trials evaluating the effect of prophylactic GTN on the prevention of PEP, improve the rate of cannulation and the prevention of hyperamylasemia. METHODS Literature searches were conducted using PubMed, EMBASE, The Cochrane Library and Web of Knowledge databases, using keywords "post-ERCP" and "pancreatitis" and limited in randomized controlled trials. RESULTS Twelve RCTs involving 2649 patients were included. Eleven RCTs compared GTN with placebo for PEP prevention. Meta-analysis showed the overall incidence of PEP was significantly reduced by GTN treatment (RR 0.67; 95% CI, 0.52-0.87). Nevertheless, GTN administration did not decrease the incidence of moderate to severe PEP (RR 0.70; 95% CI, 0.42-1.15). Subgroup analyses revealed that GTN administered by sublingual was more effective than transdermal and topical in reducing the incidence of PEP. Besides, the prophylactic effect of GTN was far more obvious in the group of high PEP incidence than in the group of low PEP incidence. Additionally, the incidence of hyperamylasemia was significantly reduced by GTN treatment (RR 0.69; 95% CI, 0.54-0.90). No differences of the successful cannulation rate of bile ducts (RR 1.03; 95% CI, 0.99-1.06) attributable to GTN were observed. CONCLUSION Prophylactic use of GTN reduced the overall incidence of PEP and hyperamylasemia. However, GTN was not helpful for the severity of PEP and the rate of cannulation.
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Affiliation(s)
- Jiexia Ding
- Department of Gastroenterology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China
| | - Xi Jin
- Department of Gastroenterology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China
| | - Yue Pan
- Department of Gastroenterology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China
| | - Shan Liu
- Department of Gastroenterology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China
| | - Youming Li
- Department of Gastroenterology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China
- * E-mail:
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Bexelius TS, Blomberg J, Lu YX, Håkansson HO, Möller P, Nordgren CE, Arnelo U, Lagergren J, Lindblad M. Losartan to prevent hyperenzymemia after endoscopic retrograde cholangiopan-creatography: A randomized clinical trial. World J Gastrointest Endosc 2012; 4:506-512. [PMID: 23189222 PMCID: PMC3506968 DOI: 10.4253/wjge.v4.i11.506] [Citation(s) in RCA: 4] [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] [Indexed: 02/05/2023] Open
Abstract
AIM: To study if the angiotensin II receptor blockers (ARB) losartan counteracts pancreatic hyperenzymemia as measured 24 h after endoscopic retrograde cholangiopancreatography (ERCP).
METHODS: A triple-blind and placebo-controlled randomized clinical trial was performed at two Swedish hospitals in 2006-2008. Patients over 18 years of age undergoing ERCP, excluding those with current pancreatitis, current use of ARB, and severe disease, such as sepsis, liver and renal failure. One oral dose of 50 mg losartan or placebo was given one hour before ERCP. The relative risk of hyperenzymemia 24 h after ERCP was estimated using multivariable logistic regression, and expressed as odds ratio with 95% confidence intervals (CIs), including adjustment for potential remaining confounding.
RESULTS: Among 76 participating patients, 38 were randomized to the losartan and the placebo group, respectively. The incidence rates of hyperenzymemia and acute pancreatitis among all 76 participating patients were 21% and 12%, respectively. Hyperenzymemia was detected in 9 and 7 patients in the losartan and placebo group, respectively. There were no major differences between the comparison groups regarding cannulation difficulty, findings, or proportion of patients requiring drainage of the bile ducts. There were, however, more pancreatic duct injections, a greater extent of pancreatography, and more biliary sphincterotomies in the losartan group than in the placebo group. Losartan was not associated with risk of hyperenzymemia compared to the placebo group after multi-varible logistic regression analysis (odds ratio 1.6, 95%CI 0.3-7.8).
CONCLUSION: In this randomized trial 50 mg losartan given orally had no prophylactic effect on development of hyperenzymemia after ERCP.
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Affiliation(s)
- Tomas Sjöberg Bexelius
- Tomas Sjöberg Bexelius, John Blomberg, Yun-Xia Lu, Jesper Lagergren, Mats Lindblad, Upper Gastrointestinal Research, Department of Molecular Medicine and Surgery, Karolinska Institutet, 176 70 Stockholm, Sweden
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Hegyi P, Rakonczay Z. The role of nitric oxide in the physiology and pathophysiology of the exocrine pancreas. Antioxid Redox Signal 2011; 15:2723-2741. [PMID: 21777142 DOI: 10.1089/ars.2011.4063] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
SIGNIFICANCE Nitric oxide (NO), a ubiquitous gaseous signaling molecule, contributes to both pancreatic physiology and pathophysiology. RECENT ADVANCES The present review provides a general overview of NO synthesis, signaling, and function. Further, it specifically discusses NO metabolism and its effects in the exocrine pancreas and focuses on the role of NO in the pathogenesis of acute pancreatitis and pancreatic ischemia/reperfusion injury. CRITICAL ISSUES Unfortunately, the role of NO in pancreatic physiology and pathophysiology remains controversial in numerous areas. Many questions regarding the messenger molecule still remain unanswered. FUTURE DIRECTIONS Probably the least is known about the downstream targets of NO, which need to be identified, especially at the molecular level.
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Affiliation(s)
- Péter Hegyi
- First Department of Medicine, University of Szeged, Szeged, Hungary
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Abstract
Pancreatitis is the most common complication of ERCP. It can be associated with substantial morbidity. Hence, the minimization of both the incidence and severity of post-ERCP pancreatitis is paramount. Considerable efforts have been made to identify factors that may be associated with an increased risk of this complication. In addition, both procedure- and pharmacological-related interventions have been proposed that may prevent this complication. This paper outlines these interventions and presents the evidence to support their use in the prevention of post-ERCP pancreatitis.
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Xu LH, Qian JB, Gu LG, Qiu JW, Ge ZM, Lu F, Wang YM, Li YM, Lu HS. Prevention of post-endoscopic retrograde cholangiopancreatography pancreatitis by epinephrine sprayed on the papilla. J Gastroenterol Hepatol 2011; 26:1139-44. [PMID: 21392105 DOI: 10.1111/j.1440-1746.2011.06718.x] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
BACKGROUND AND AIM Epinephrine sprayed on the papilla may reduce papillary edema and prevent acute pancreatitis after endoscopic retrograde cholangiopancreatography (ERCP). The aim of this study was to evaluate the effects of localized irrigation with epinephrine saline for prevention of post-ERCP pancreatitis (PEP). METHODS A total of 941 patients who were scheduled for ERCP were recruited into this study. We randomized the patients to have 20 mL of either 0.02% epinephrine or saline sprayed on the papilla after diagnostic ERCP to prevent post-ERCP pancreatitis. We recorded duct visualization, presence of pancreatic acinarization, number of injections into the pancreatic duct, total volume of contrast used, and procedure duration. The serum amylase levels were measured at 6, 24 and 48 h after ERCP. We counted the patients of PEPs and compared whether there was significant difference between the pancreatitis group and the no pancreatitis group. RESULTS A univariate analysis of the explanatory variables between the epinephrine and control groups, the pancreatitis and no pancreatitis groups revealed the treatment to be effective, but most of the groups were not statistically significant. PEPs occurred in 40 of the 941 patients (4.25%), the incidence of pancreatitis tended to be higher in the control group (31/480, 6.45%) than in the epinephrine group (9/461, 1.95%) (P = 0.0086). CONCLUSIONS Epinephrine sprayed on the papilla may be effective to prevent PEP. Female patients (aged ≥ 18 years and < 35 years) (7/40, 17.5%), common bile duct diameter < 10 mm (27/40, 67.5%), previous cholangitis (3/40, 7.5%), body mass index ≥ 24 (22/40, 55%), and/or serum triglycerides ≥ 5.65 mmol/L (6/40, 15%), might be risk factors for post-ERCP pancreatitis, but are not statistically significant in the study.
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Affiliation(s)
- Li Hua Xu
- Department of Gastroenterology, The First People's Hospital of Nantong, Jiangsu, China.
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Intravenous synthetic secretin reduces the incidence of pancreatitis induced by endoscopic retrograde cholangiopancreatography. Pancreas 2011; 40:533-9. [PMID: 21499206 DOI: 10.1097/mpa.0b013e3182152eb6] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
OBJECTIVES This study aimed to evaluate whether synthetic secretin is effective in reducing post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis. METHODS This is a single academic medical center, prospective, randomized, double-blind, placebo-controlled trial using secretin (dose of 16 μg) administered intravenously immediately before ERCP. Patients were evaluated for the primary outcome of post-ERCP pancreatitis as diagnosed by a single investigator. RESULTS A total of 1100 patients were screened, of whom 869 were randomly assigned to receive secretin (n = 426) or placebo (n = 443) before ERCP and were evaluated after the procedure for efficacy of secretin. The incidence of pancreatitis in the secretin group compared with the placebo group was 36 (8.7%) of 413 patients versus 65 (15.1%) of 431 patients, respectively, P = 0.004. In the subgroup analysis, secretin was highly protective against post-ERCP pancreatitis for patients undergoing biliary sphincterotomy (6/129 vs 32/142, P < 0.001), patients undergoing cannulation of the common bile duct (26/339 vs 56/342, P < 0.001), and patients not undergoing pancreatic sphincterotomy (26/388 vs 57/403, P = 0.001). Analysis of the interaction between these groups reveals that the primary effect of secretin prophylaxis was prevention of post-ERCP pancreatitis in patients undergoing biliary sphincterotomy. CONCLUSIONS Synthetic secretin reduces the risk of post-ERCP pancreatitis, particularly in patients in undergoing biliary sphincterotomy.
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Lee CT, Lee TL, Liao WC, Chang CY, Tai CM, Chiang TH, Tu CH, Tseng WK, Lin JT. Myocardial ischemia during endoscopic retrograde cholangiopancreatography: an overlooked issue with significant clinical impact. J Gastroenterol Hepatol 2010; 25:1518-24. [PMID: 20796149 DOI: 10.1111/j.1440-1746.2010.06274.x] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/16/2023]
Abstract
BACKGROUND AND AIM The occurrence of peri-procedural myocardial ischemia with endoscopic retrograde cholangiopancreatography (ERCP) has been documented, but its significance remains controversial. This study aimed to investigate the incidence and risk factors of myocardial ischemia during ERCP procedures and to analyze the potential association between myocardial ischemia and post-ERCP complications. METHODS Ambulatory 24-h ST-segment monitoring from 30 min prior to 24 h after ERCP was obtained on 71 patients from September 2006 to August 2007. Changes in vital signs during ERCP, post-ERCP complications, and their outcomes were recorded and analyzed. RESULTS Cardiac ischemia occurred in 13 patients (18.3%) during ERCP and one patient developed myocardial infarction. More patients in the ischemic group (38.5%) than in the non-ischemic group (5.2%) had ST-T changes in pre-ERCP resting electrocardiography (P < 0.01). Hypotension during ERCP was found only in the ischemic group (15.4% vs 0%; P = 0.03). Patients with cardiac ischemia during ERCP had a significantly higher rate of elevated serum amylase and lipase levels (53.8% vs 15.5%; P < 0.01) and post-ERCP pancreatitis (30.8% vs 6.9%; P = 0.03). Multivariable logistic regression analysis revealed that cardiac ischemia during ERCP (OR: 5.21, P = 0.050) and pancreatic duct cannulation (OR: 5.7, P = 0.036) were independent predictors for post-ERCP pancreatitis. CONCLUSIONS ST-T changes on resting electrocardiography and intra-procedural hypotension are risk factors of myocardial ischemia during ERCP. Post-ERCP hyperamylasemia, hyperlipasemia, and pancreatitis were associated with myocardial ischemia during ERCP.
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Affiliation(s)
- Ching-Tai Lee
- Division of Gastroenterology, Department of Internal Medicine, E-Da Hospital/I-Shou University, Kaohisung, Taiwan
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Chen B, Fan T, Wang CH. A meta-analysis for the effect of prophylactic GTN on the incidence of post-ERCP pancreatitis and on the successful rate of cannulation of bile ducts. BMC Gastroenterol 2010; 10:85. [PMID: 20673365 PMCID: PMC2921391 DOI: 10.1186/1471-230x-10-85] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/02/2009] [Accepted: 07/31/2010] [Indexed: 02/05/2023] Open
Abstract
Background Glyceryl trinitrate (GTN) has been shown to be able to relax the sphincter of Oddi (SO) both in animals and humans. Theoretically, the use of these compounds during and after endoscopic retrograde cholangiopancreatgraphy (ERCP) could relax the biliary and pancreatic sphincters, facilitating cannulation of common bile duct (CBD) during the procedure, or minimizing potential pancreatic outflow obstruction after the procedure. However, clinical trials evaluating the protective effect of GTN on the post-endoscopic retrograde cholangiopancreatgraphy pancreatitis (PEP) have yielded inconclusive results. This meta-analysis is to systematically assess the effect of prophylactic administration of glyceryl trinitrate (GTN) on the prevention of PEP and the effect on the cannulation of bile ducts. Methods By searching PubMed (1966 to September 2009), CENTRAL (Cochrane Controlled trials Register; issue 3, 2009) and EMBASE.com (1984 to September 2009), two independent reviewers systematically identified prospective randomized controlled trials (RCTs) detecting the effect of prophylactic GTN on the incidence of PEP and on the cannulation of bile ducts. A meta-analysis of these clinical trials was then performed. Results There are 55/899(6.1%) patients suffering PEP in the treatment group versus 95/915(10.4%) patients in the placebo group. The overall pooled risk of PEP was significantly lower in the GTN group than in the placebo group (OR 0.56, 95% CI: 0.40 to 0.79, p = 0.001). Subgroup analyses suggested that GTN administered by the sublingual form (OR 0.34,95% CI:0.16 to 0.75, p = 0.007) is more effective than transdermal route(OR 0.64,95% CI:0.40 to 1.01, p = 0.05), and the protective effect of GTN was far more obvious in the centers with high incidence of PEP (OR 0.40, 95% CI:0.24 to 0.67, p = 0.0006) than those centers with a low incidence of PEP (OR 0.75, 95% CI: 0.47 to 1.20, p = 0.22). Additionally, the meta-analysis suggests that GTN was not helpful for the cannulation of bile ducts. Conclusion We concluded that prophylactic administration of GTN may significantly reduce the incidence of PEP and not be helpful for the cannulation of bile ducts.
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Affiliation(s)
- Bin Chen
- Department of Gastroenterology, West China Hospital, Sichuan University, 37# Guoxue Road, Chengdu, 610041, China
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Woods KE, Willingham FF. Endoscopic retrograde cholangiopancreatography associated pancreatitis: A 15-year review. World J Gastrointest Endosc 2010; 2:165-78. [PMID: 21160744 PMCID: PMC2998911 DOI: 10.4253/wjge.v2.i5.165] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/15/2010] [Revised: 04/29/2010] [Accepted: 05/06/2010] [Indexed: 02/06/2023] Open
Abstract
The aim of this article is to review the literature regarding post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis. We searched for and evaluated all articles describing the diagnosis, epidemiology, pathophysiology, morbidity, mortality and prevention of post-ERCP pancreatitis (PEP) in adult patients using the PubMed database. Search terms included endoscopic retrograde cholangiopancreatography, pancreatitis, ampulla of vater, endoscopic sphincterotomy, balloon dilatation, cholangiography, adverse events, standards and utilization. We limited our review of articles to those published between January 1, 1994 and August 15, 2009 regarding human adults and written in the English language. Publications from the reference sections were reviewed and included if they were salient and fell into the time period of interest. Between the dates queried, seventeen large (> 500 patients) prospective and four large retrospective trials were conducted. PEP occurred in 1%-15% in the prospective trials and in 1%-4% in the retrospective trials. PEP was also reduced with pancreatic duct stent placement and outcomes were improved with endoscopic sphincterotomy compared to balloon sphincter dilation in the setting of choledocholithiasis. Approximately 34 pharmacologic agents have been evaluated for the prevention of PEP over the last fifteen years in 63 trials. Although 22 of 63 trials published during our period of review suggested a reduction in PEP, no pharmacologic therapy has been widely accepted in clinical use in decreasing the development of PEP. In conclusion, PEP is a well-recognized complication of ERCP. Medical treatment for prevention has been disappointing. Proper patient selection and pancreatic duct stenting have been shown to reduce the complication rate in randomized clinical trials.
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Affiliation(s)
- Kevin E Woods
- Kevin E Woods, Department of Medicine, Gastrointestinal Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, United States
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Nitroglycerin in the prevention of post-ERCP pancreatitis: a meta-analysis. Dig Dis Sci 2010; 55:1-7. [PMID: 19160042 DOI: 10.1007/s10620-008-0709-9] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/27/2008] [Accepted: 12/30/2008] [Indexed: 12/11/2022]
Abstract
The objective of this research paper is to evaluate the effect of prophylactic nitroglycerin in the prevention of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) by performing a meta-analysis of randomized controlled trials (RCTs). Electronic databases, including PubMed, EMBASE, the Cochrane library, and the Science Citation Index, were searched to retrieve relevant trials. Outcome measures were the incidence of PEP. Four RCTs, enrolling a total of 856 patients, were included. Meta-analysis of these trials indicated a significant association between the use of nitroglycerin and the reduction of PEP (RR 0.60; 95%CI: 0.39-0.92; P = 0.02). However, subsequent sensitive analysis failed to confirm that nitroglycerin was statistically superior to a placebo in reducing PEP (RR 0.68; 95%CI: 0.41-1.11; P = 0.12). Based on the limitations in this meta-analysis, prophylactic use of nitroglycerine for all patients who underwent ERCP is not recommended. Further clinical trials are required to confirm the effect of nitroglycerin in the prevention of PEP.
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Monfared SSMS, Vahidi H, Abdolghaffari AH, Nikfar S, Abdollahi M. Antioxidant therapy in the management of acute, chronic and post-ERCP pancreatitis: a systematic review. World J Gastroenterol 2009; 15:4481-4490. [PMID: 19777606 PMCID: PMC2751992 DOI: 10.3748/wjg.15.4481] [Citation(s) in RCA: 37] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/25/2009] [Revised: 08/03/2009] [Accepted: 08/10/2009] [Indexed: 02/06/2023] Open
Abstract
We systematically reviewed the clinical trials which recruited antioxidants in the therapy of pancreatitis and evaluated whether antioxidants improve the outcome of patients with pancreatitis. Electronic bibliographic databases were searched for any studies which investigated the use of antioxidants in the management of acute pancreatitis (AP) or chronic pancreatitis (CP) and in the prevention of post-endoscopic retrograde cholangio-pancreatography (post-ERCP) pancreatitis (PEP) up to February 2009. Twenty-two randomized, placebo-controlled, clinical trials met our criteria and were included in the review. Except for a cocktail of antioxidants which showed improvement in outcomes in three different clinical trials, the results of the administration of other antioxidants in both AP and CP clinical trials were incongruent and heterogeneous. Furthermore, antioxidant therapy including allopurinol and N-acetylcysteine failed to prevent the onset of PEP in almost all trials. In conclusion, the present data do not support a benefit of antioxidant therapy alone or in combination with conventional therapy in the management of AP, CP or PEP. Further double blind, randomized, placebo-controlled clinical trials with large sample size need to be conducted.
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Senol A, Saritas U, Demirkan H. Efficacy of intramuscular diclofenac and fluid replacement in prevention of post-ERCP pancreatitis. World J Gastroenterol 2009; 15:3999-4004. [PMID: 19705494 PMCID: PMC2731949 DOI: 10.3748/wjg.15.3999] [Citation(s) in RCA: 40] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To assess the efficacy of intramuscular diclofenac and fluid replacement for prevention of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis.
METHODS: A prospective, placebo-controlled study was conducted in 80 patients who underwent ERCP. Patients were randomized to receive parenteral diclofenac at a loading dose of 75 mg followed by the infusion of 5-10 mL/kg per hour isotonic saline over 4 h after the procedure, or the infusion of 500 mL isotonic saline as placebo. Patients were evaluated clinically, and serum amylase levels were measured 4, 8 and 24 h after the procedure.
RESULTS: The two groups were matched for age, sex, underlying disease, ERCP findings, and type of treatment. The overall incidence of pancreatitis was 7.5% in the diclofenac group and 17.5% in the placebo group (12.5% in total). There were no significant differences in the incidence of pancreatitis and other variables between the two groups. In the subgroup analysis, the frequency of pancreatitis in the patients without sphincter of Oddi dysfunction (SOD) was significantly lower in the diclofenac group than in the control group (P = 0.047).
CONCLUSION: Intramuscular diclofenac and fluid replacement lowered the rate of pancreatitis in patients without SOD.
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Bang UC, Nøjgaard C, Andersen PK, Matzen P. Meta-analysis: Nitroglycerin for prevention of post-ERCP pancreatitis. Aliment Pharmacol Ther 2009; 29:1078-85. [PMID: 19236312 DOI: 10.1111/j.1365-2036.2009.03978.x] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
BACKGROUND Acute pancreatitis after ERCP is a severe side effect. AIM To evaluate the preventive effect of nitroglycerin on post-ERCP pancreatitis by a meta-analysis of randomized clinical studies. METHODS We searched on Pubmed, Embase, Cochrane Library and all abstracts presented at Digestive Disease Week and United European Gastrointestinal Week from 2004 to 2008. We used the MeSH terms 'pancreatitis' together (AND) with the terms: 'glyceryl trinitrate', 'glyceryl dinitrate', 'isosorbide dinitrate' or 'nitroglycerin'. RESULTS Five clinical studies evaluating the incidence of post-ERCP pancreatitis after administration of nitroglycerin were identified. Meta-analysis including all five studies showed a relative risk (RR) of 0.61 (95% CI; 0.44, 0.86) with the number needed to treat (NNT) of 26 (95% CI: 16, 82). Three studies evaluated nitroglycerin administered by a dermal patch reaching together an RR of 0.66 (95% CI; 0.43, 1.01). The use of nitroglycerin is associated with a significantly increased risk of hypotension (RR 2.25) and headache (RR 3.64). No difference in mortality was observed. CONCLUSIONS Overall, our meta-analysis supports the use of nitroglycerin in the prevention of post-ERCP pancreatitis, but administration of nitroglycerin by the dermal route, which is the preferred route of administration, did not reach statistical significance.
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Affiliation(s)
- U C Bang
- Department of Endocrinology, Hvidovre Hospital, Hvidovre, Denmark.
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Nøjgaard C, Hornum M, Elkjaer M, Hjalmarsson C, Heyries L, Hauge T, Bakkevold K, Andersen PK, Matzen P. Does glyceryl nitrate prevent post-ERCP pancreatitis? A prospective, randomized, double-blind, placebo-controlled multicenter trial. Gastrointest Endosc 2009; 69:e31-7. [PMID: 19410035 DOI: 10.1016/j.gie.2008.11.042] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/26/2008] [Accepted: 11/20/2008] [Indexed: 02/08/2023]
Abstract
OBJECTIVE Acute pancreatitis is the most dreaded complication of ERCP. Two studies have shown a significant effect of glyceryl nitrate (GN) in preventing post-ERCP pancreatitis (PEP). We wanted to evaluate this promising effect in a larger study with a realistically precalculated incidence of PEP. DESIGN/PATIENTS A randomized, double-blind, placebo-controlled multicenter study including patients from 14 European centers was performed. A total of 820 patients were entered; 806 were randomized. INTERVENTION The active drug was transdermal GN (Discotrine/Minitran, 3M Pharma) 15 mg/24 hours; placebo (PL) was an identical-looking patch applied before ERCP. A total of 401 patients received GN; 405 received PL. RESULTS Forty-seven patients had PEP (5.8%), 18 (4.5%) in the GN group and 29 (7.1%) in the PL group. The relative risk reduction of PEP in the GN group of 36% (95% CI, 11%-65%) compared with the PL group was not statistically significant (P = .11). Thirteen had mild pancreatitis (4 in the GN group, 9 in the PL group), 26 had moderate pancreatitis (9 in the GN group, 17 in the PL group), and 8 had severe pancreatitis (5 in the GN group, 3 in the PL group). Headache (P < .001) and hypotension (P = .006) were more common in the GN group. Significant variables predictive of PEP were not having biliary stones extracted; hypotension after ERCP; morphine, propofol, glucagon, and general anesthesia during the procedure; or no sufentanil during the procedure. CONCLUSIONS The trial showed no statistically significant preventive effect of GN on PEP. Because of a considerable risk of a type II error, an effect of GN may have been overlooked. (ClinicalTrials.gov ID: NCT00121901.).
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Affiliation(s)
- Camilla Nøjgaard
- Department of Gastroenterology, Hvidovre Hospital, Hvidovre, Denmark
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Matsushita M, Takakuwa H, Shimeno N, Uchida K, Nishio A, Okazaki K. Epinephrine sprayed on the papilla for prevention of post-ERCP pancreatitis. J Gastroenterol 2009; 44:71-5. [PMID: 19159075 DOI: 10.1007/s00535-008-2272-8] [Citation(s) in RCA: 28] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/14/2007] [Accepted: 08/07/2008] [Indexed: 02/04/2023]
Abstract
BACKGROUND Epinephrine sprayed on the papilla may reduce papillary edema and thus prevent acute pancreatitis after endoscopic retrograde cholangiopancreatography (ERCP). The aim of this study was to determine the efficacy of this technique for prevention of post- ERCP pancreatitis. METHODS Patients scheduled for ERCP were recruited into this study. We randomized the patients to have 10 ml of either 0.02% epinephrine (epinephrine group) or saline (control group) sprayed on the papilla after diagnostic ERCP and prospectively analyzed the occurrence of post-ERCP pancreatitis between the groups. We recorded duct visualization, presence of pancreatic acinarization, number of injections into the pancreatic duct, total volume of contrast used, and procedure duration. RESULTS There was no significant difference between the groups with regard to visualization of the bile duct and/or the main and accessory pancreatic ducts, presence of pancreatic acinarization, number of injections into the pancreatic duct, total volume of contrast used, and procedure duration. Overall, post-ERCP pancreatitis occurred in 4 of the 370 patients (1.1%). The incidence of pancreatitis tended to be higher in the control group (4/185) than in the epinephrine group (0/185) (P = 0.1230). CONCLUSIONS Epinephrine sprayed on the papilla tended to prevent post-ERCP pancreatitis, although it was not statistically significant because of the low incidence of pancreatitis. Further studies on the efficacy of this technique in patients at high risk for pancreatitis, and on other volumes and/or concentrations of epinephrine, are warranted.
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Affiliation(s)
- Mitsunobu Matsushita
- Third Department of Internal Medicine, Kansai Medical University, 2-3-1 Shinmachi, Hirakata, 573-1191, Japan
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Sherman S, Alazmi WM, Lehman GA, Geenen JE, Chuttani R, Kozarek RA, Welch WD, Souza S, Pribble J. Evaluation of recombinant platelet-activating factor acetylhydrolase for reducing the incidence and severity of post-ERCP acute pancreatitis. Gastrointest Endosc 2009; 69:462-472. [PMID: 19231487 DOI: 10.1016/j.gie.2008.07.040] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/09/2006] [Accepted: 07/22/2008] [Indexed: 12/11/2022]
Abstract
BACKGROUND Pancreatitis is the most common major complication of diagnostic and therapeutic ERCP. Platelet-activating factor (PAF) has been implicated in the pathophysiologic events associated with acute pancreatitis. Animal and human studies suggested that recombinant PAF acetylhydrolase (rPAF-AH) might ameliorate the severity of acute pancreatitis. OBJECTIVE Our purpose was to determine whether prophylactic rPAF-AH administration reduces the frequency or severity of post-ERCP pancreatitis in high-risk patients. DESIGN Randomized, multicenter, double-blind, placebo-controlled study. INTERVENTIONS Patients received rPAF-AH at a dose of either 1 or 5 mg/kg or placebo. Patients were administered a single intravenous infusion over 10 minutes of study drug or placebo <1 hour before ERCP. MAIN OUTCOME MEASUREMENTS Standardized criteria were used to diagnose and grade the severity of post-ERCP pancreatitis. Adverse events were prospectively recorded. RESULTS A total of 600 patients were enrolled. There were no statistically significant differences among the treatment groups with respect to patient demographics, ERCP indications, and patient and procedure risk factors for post-ERCP pancreatitis with the following exceptions: the rPAF-AH 5 mg/kg group had significantly fewer patients younger than 40 years old and scheduled to undergo a therapeutic ERCP involving the pancreatic sphincter or duct. Post-ERCP pancreatitis occurred in 17.5%, 15.9%, and 19.6% of patients receiving rPAF-AH (1 mg/kg), rPAF-AH (5 mg/kg), and placebo, respectively (P = .59 for rPAF-AH 1 mg/kg vs placebo and P = .337 for rPAF-AH 5 mg/kg vs placebo). There was no statistically significant difference between the groups with regard to the severity of pancreatitis, frequency of amylase/lipase elevation more than 3 times normal, or abdominal pain. CONCLUSIONS There was no apparent benefit of rPAF-AH treatment compared with placebo in reducing the incidence of post-ERCP pancreatitis in subjects at increased risk.
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Affiliation(s)
- Stuart Sherman
- Indiana University Medical Center, Indianapolis, Indiana, USA
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Hao JY, Wu DF, Wang YZ, Gao YX, Lang HP, Zhou WZ. Prophylactic effect of glyceryl trinitrate on post-endoscopic retrograde cholangiopancreatography pancreatitis: A randomized placebo-controlled trial. World J Gastroenterol 2009; 15:366-8. [PMID: 19140238 PMCID: PMC2653335 DOI: 10.3748/wjg.15.366] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To examine the prophylactic effect of glyceryl trinitrate on post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis and hyperamylasemia.
METHODS: Patients scheduled for ERCP were randomly divided into study group and placebo group. Patients in study group and placebo group were treated with 5 mg glyceryl trinitrate and 100 mg vitamin C, respectively, 5 min before endoscopic maneuvers.
RESULTS: A total of 74 patients were enrolled in the final analysis. Post-ERCP pancreatitis occurred in 3 patients (7.9%) of the study group and 9 patients (25%) in the placebo group (P = 0.012). Hyperamylasemia occurred in 8 patients of the study group (21.1%) and 13 patients (36.1%) of the placebo group (P = 0.037).
CONCLUSION: Glyceryl trinitrate before ERCP can effectively prevent post-ERCP and hyperamylasemia.
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Khoshbaten M, Khorram H, Madad L, Ehsani Ardakani MJ, Farzin H, Zali MR. Role of diclofenac in reducing post-endoscopic retrograde cholangiopancreatography pancreatitis. J Gastroenterol Hepatol 2008; 23:e11-6. [PMID: 17683501 DOI: 10.1111/j.1440-1746.2007.05096.x] [Citation(s) in RCA: 77] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND AND AIMS Acute pancreatitis following endoscopic retrograde cholangiography presents a unique opportunity for prophylaxis and early modification of the disease process because the initial triggering event is temporally well defined and takes place in the hospital. We report a prospective, single-center, randomized, double-blind controlled trial to determine if rectal diclofenac reduces the incidence of pancreatitis following cholangiopancreatography. METHODS Entry to the trial was restricted to patients who underwent endoscopic retrograde pancreatography. Immediately after endoscopy, patients were given a suppository containing either 100 mg diclofenac or placebo. Estimation of serum amylase level and clinical evaluation were performed in all patients. RESULTS One hundred patients entered the trial, and 50 received rectal diclofenac. Fifteen patients developed pancreatitis (15%), of whom two received rectal diclofenac and 13 received placebo (P < 0.01). CONCLUSIONS This trial shows that rectal diclofenac given immediately after endoscopic retrograde cholangiopancreatography can reduce the incidence of acute pancreatitis.
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Low-dose heparin for the prevention of post-ERCP pancreatitis: a randomized placebo-controlled trial. Surg Endosc 2008; 22:1971-6. [PMID: 18214607 DOI: 10.1007/s00464-007-9738-2] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2007] [Revised: 11/15/2007] [Accepted: 12/11/2007] [Indexed: 12/19/2022]
Abstract
BACKGROUND As suggested by observational and animal studies, heparin has antiinflammatory effects that could prevent acute post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis. Low-molecular-weight heparin did not reduce the incidence of post-ERCP pancreatitis in a controlled study. The current study aimed to determine whether prophylactic administration of low-dose unfractionated heparin, which has potentially more antiinflammatory capability, can prevent acute post-ERCP pancreatitis. METHODS Patients scheduled for ERCP in the authors' department were randomized to receive unfractionated heparin (5,000 IU) or placebo (saline solution 0.5 ml) administered subcutaneously 20 to 30 min before the ERCP. Patients who had undergone endoscopic sphincterotomy in the past were excluded from the study. Post-ERCP pancreatitis was defined according to criteria established by Cotton: abdominal pain combined with a threefold elevation of blood amylase 24 h after the ERCP. RESULTS The study enrolled 106 patients. One patient was excluded from the analysis due to inaccessible papilla of Vater, leaving 51 patients in the heparin group and 54 in the placebo group, for a total of 105 patients (62 women and 43 men) with a mean age of 64.6 years. The rate of post-ERCP pancreatitis was not different between the groups (heparin, 4 patients, 7.8%; placebo, 4 patients, 7.4%). Two patients in each group experienced mild bleeding. CONCLUSIONS The study did not demonstrate a significant effect of low-dose unfractionated heparin in the prevention of post-ERCP pancreatitis. A multicenter trial with a larger number of patients is needed to demonstrate a benefit from this drug.
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Risks of Endoscopic Retrograde Cholangiopancreatography and Sphincterotomy. TECHNIQUES IN GASTROINTESTINAL ENDOSCOPY 2008. [DOI: 10.1016/j.tgie.2007.08.006] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
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Cheon YK, Cho KB, Watkins JL, McHenry L, Fogel EL, Sherman S, Schmidt S, Lazzell-Pannell L, Lehman GA. Efficacy of diclofenac in the prevention of post-ERCP pancreatitis in predominantly high-risk patients: a randomized double-blind prospective trial. Gastrointest Endosc 2007; 66:1126-32. [PMID: 18061712 DOI: 10.1016/j.gie.2007.04.012] [Citation(s) in RCA: 78] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/14/2006] [Accepted: 04/09/2007] [Indexed: 02/08/2023]
Abstract
BACKGROUND Pancreatitis is one of the major complications of ERCP and endoscopic sphincterotomy. It has been shown that nonsteriodal anti-inflammatory drugs are potent inhibitors of phospholipase A(2), activity which is increased in pancreatitis. A previous study showed reduction of post-ERCP pancreatitis with administration of rectal diclofenac. OBJECTIVE The aim of this study was to determine whether prophylactic oral diclofenac will reduce the incidence and the severity of ERCP-induced pancreatitis, especially in high-risk patients. DESIGN Single-center, randomized, double-blinded, prospective study. SETTING Indiana University Medical Center. PATIENTS A total of 207 evaluable patients were randomized to receive either diclofenac 50 mg or placebo by mouth 30 to 90 minutes before and 4 to 6 hours after ERCP. RESULTS The groups were similar with regard to patient demographics and to patient and procedure risk factors for post-ERCP pancreatitis. The overall incidence of post-ERCP pancreatitis was 16.4%. It occurred in 17 of 102 patients in the control group (16.7%) and in 17 of 105 patients in diclofenac group (16.2%). The pancreatitis was graded mild in 9.8%, moderate in 5.9%, and severe 1.0% of the control group, and mild in 10.5%, moderate in 4.8%, and severe in 1.0% of the diclofenac group. In high-risk patients, the incidence of post-ERCP pancreatitis was 17.3%. It occurred in 18.0% (16/89) in the control group and in 17.8% (16/90) in the diclofenac group. There was no significant difference between the groups in the frequency or severity of post-ERCP pancreatitis in overall and high-risk patients; however, the power of the study was less than 45%. CONCLUSIONS Prophylactic orally administered diclofenac was not observed to affect the frequency or severity of post-ERCP pancreatitis in high-risk patients.
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Affiliation(s)
- Young Koog Cheon
- Indiana University Medical Center; Indianapolis, Indiana 46202, USA
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Abstract
Nitric oxide (NO) is a gaseous neurotransmitter, a vasodilator and paracrine regulator. In the pancreas, NO regulates normal pancreatic exocrine secretion, endocrine pancreatic insulin secretion and pancreatic microvascular blood flow. NO has multiple species and is produced de novo by 3 NO synthase enzymes. Endothelial NO synthase reduces the severity of the initial phase of experimental acute pancreatitis (AP). Cigarette smoking and chronic alcohol use disrupt normal NO pathways and are associated with pancreatitis and pancreatic cancer. The aims of this minireview are to describe normal intrapancreatic NO pathways, perturbations during experimental AP and due to epidemiological factors associated with pancreatic pathology, and the clinical implications of NO on AP.
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Affiliation(s)
- Matthew J DiMagno
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, University of Michigan School of Medicine, Ann Arbor, MI 48109, USA.
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Abstract
PURPOSE OF REVIEW We endeavor to review important new advances in acute pancreatitis made in the past year. We focused on clinical aspects of acute pancreatitis, which contained new observations or insights into new or old concepts. For experimental acute pancreatitis we refer readers to a recent comprehensive review. RECENT FINDINGS Recently, case fatality rates of acute pancreatitis have stabilized; carbohydrate-deficient transferrin was shown to predict alcoholic acute pancreatitis; idiopathic chronic pancreatitis or occult cholelithiasis have been associated with 'recurrent acute pancreatitis' in most patients; and cystic fibrosis transmembrane conductance regulator genetic mutations were frequently found (10-50%) in patients with recurrent acute pancreatitis. In addition, alcohol was shown to increase the risk of pancreatic necrosis regardless of the cause of acute pancreatitis. Persistent organ failure and multiple organ dysfunction syndrome but not necessarily extent of necrosis were demonstrated to predict increased mortality in acute pancreatitis. Chemoprevention of post-endoscopic retrograde cholangiopancreatography acute pancreatitis remains unproven. Enteral feeding has been strongly recommended in severe acute pancreatitis. Finally, data are lacking for routine, prophylactic antibiotic administration to all patients with pancreatic necrosis. SUMMARY We reviewed studies this past year that further characterize the epidemiology, etiology and risk stratification of acute pancreatitis. Evolving areas include chemoprevention of post-endoscopic retrograde cholangiopancreatography acute pancreatitis and enteral feeding and antibiotics in severe acute pancreatitis. We await translation of novel therapies from the bench to bedside.
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Affiliation(s)
- Matthew J DiMagno
- University of Michigan Medical School, Division of Gastroenterology and Hepatology, Department of Internal Medicine, Ann Arbor, Michigan, USA.
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Haciahmetoglu T, Ertekin C, Dolay K, Yanar F, Yanar H, Kapran Y. The effects of contrast agent and intraductal pressure changes on the development of pancreatitis in an ERCP model in rats. Langenbecks Arch Surg 2007; 393:367-72. [PMID: 17674029 DOI: 10.1007/s00423-007-0214-1] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2006] [Accepted: 07/13/2007] [Indexed: 01/14/2023]
Abstract
OBJECTIVE Although there are various experimental pancreatic models in animals, only a few studies have evaluated how intraductal pressure and contrast agent affect the development of pancreatitis after endoscopic retrograde cholangiopancreatograpy (ERCP). MATERIALS AND METHODS The rats were randomly divided into seven groups (n = 8/group). The rats in all groups underwent laparotomy and their biliopancreatic ducts were cannulated transduodenally using a 24G catheter. In the control group, group 1, the biliopancreatic ducts of the rats were not infused with any fluid. The biliopancreatic ducts of the rats in groups 2, 3, and 4 were infused with 0.5 ml isotonic NaCl solution at 10, 2, and 50 mmHg, respectively. Groups 5, 6, and 7 were given 0.5 ml of 50% diluted contrast agent at 10, 25, and 50 mmHg, respectively. The serum amylase, aspartate aminotransferase (AST), lactic dehydrogenase (LDH), and C-reactive protein (CRP) were measured 24 h after the procedure. Pancreatic tissue was also evaluated histopathologically. RESULTS Pancreatitis due to the contrast agent was noted when comparing the low pressure isotonic NaCl group and the low pressure contrast group (p < 0.05). Based on serum amylase and CRP values, there was a positive correlation between the severity and frequency of acute pancreatitis and pressure (p < 0.01). AST and LDH levels increased in all of the groups that underwent the procedure; however, no correlation was detected with increasing pressure or with the use of contrast agent (p > 0.05). Both pancreatic edema and the inflammatory cell infiltration score were elevated in isotonic NaCl and contrast group (p < 0.05); however, necrosis was not significantly changed (p > 0.05). CONCLUSION The results of this study suggest that the main mechanism for preventing pancreatitis after ERCP is to minimize trauma to the pancreatic canal, to cannulate the pancreas only when it is necessary, and to give contrast agent under low pressure when it is needed.
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Lieb JG, Draganov PV. Early successes and late failures in the prevention of post endoscopic retrograde cholangiopancreatography. World J Gastroenterol 2007; 13:3567-74. [PMID: 17659706 PMCID: PMC4146795 DOI: 10.3748/wjg.v13.i26.3567] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Acute pancreatitis is the most common complication of endoscopic retrograde cholangiopancreatography (ERCP). The only way to prevent this complication is to avoid an ERCP all together. Because of the risks involved, a careful consideration should be given to the indication for ERCP and the potential risk/benefit ratio of the test. Once a decision to perform an ERCP is made, the procedure should be carried out with meticulous care by an experienced endoscopist, and with a minimum of pancreatic duct opacification. Several pharmacologic agents have been tested, but to date the most important method of reducing post ERCP pancreatitis is the placement of pancreatic stent. Pancreatic stents should be placed in all patients at high risk of this complication such as those undergoing pancreatic sphincterotomy, pancreatic duct manipulation and intervention, and patients with suspected sphincter of Oddi dysfunction. Pancreatic stents should be also considered in patients requiring precut sphincterotomy to gain biliary access.
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Affiliation(s)
- John G Lieb
- Division of Gastroenterology, Department of Internal Medicine, University of Florida, Gainesville, FL 32610- 0214, USA
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Abstract
Pancreatitis is the most common complication after endoscopic retrograde cholangio-pancreatography (ERCP); the reported incidence of this complication varies from less than 1% to 40%, but a rate of 4%-8% is reported in most prospective studies involving non-selected patients. Differences in criteria for defining pancreatitis, methods of data collection, and patient populations (i.e. number of high-risk patients included in the published series) are factors that are likely to affect the varying rates of post-ERCP pancreatitis. The severity of post-ERCP pancreatitis (PEP) can range from a minor inconvenience with one or two days of added hospitalization with full recovery to a devastating illness with pancreatic necrosis, multiorgan failure, permanent disability, and even death. Although, most episodes of PEP are mild (about 90%), a small percentage of patients (about 10%) develop moderate or severe pancreatitis. In the past, PEP was often viewed as an unpredictable and unavoidable complication, with no realistic strategy for its avoidance. New data have aided in stratification of patients into PEP risk categories and new measures have been introduced to decrease the risk of PEP. As most ERCPs are performed on an outpatient basis, the majority of patients will not develop PEP and can be discharged. Alternatively, early detection of those patients who will go on to develop PEP can guide decisions regarding hospital admission and aggressive management. In the last decade, great efforts have been addressed toward prevention of this complication. Points of emphasis have included technical measures, pharmacological prophylaxis, and patient selection. This review provides a comprehensive, evidence-based assessment of published data on PEP and current suggestions for its avoidance.
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Affiliation(s)
- Ayman M Abdel Aziz
- Division of Gastroenterology and Hepatology, Indiana University Medical Center, Indianapolis, IN 46202, USA
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Sotoudehmanesh R, Khatibian M, Kolahdoozan S, Ainechi S, Malboosbaf R, Nouraie M. Indomethacin may reduce the incidence and severity of acute pancreatitis after ERCP. Am J Gastroenterol 2007; 102:978-83. [PMID: 17355281 DOI: 10.1111/j.1572-0241.2007.01165.x] [Citation(s) in RCA: 147] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVES Acute pancreatitis is the most common complication of endoscopic retrograde cholangiopancreatography (ERCP). Many medications have been used to prevent this complication. We aimed to evaluate the efficacy of rectally administered indomethacin for the prevention of post-ERCP pancreatitis. METHODS During 18 months, all eligible patients who underwent ERCP were enrolled in this study. In a double-blind randomized trial, patients received a suppository containing indomethacin, 100 mg, or an inert placebo immediately before ERCP. Serum amylase levels and clinically pertinent evaluations were measured in all patients after ERCP. RESULTS A total of 490 patients entered the trial, of which half received indomethacin. Twenty-two patients developed pancreatitis; seven cases in the indomethacin group and 15 in the placebo group (P=0.06). Pancreatic duct injection (OR=3.0, 95% CI: 1.3-7.4), pancreatic duct cannulation more than once (OR=4.2, 95% CI: 1.7-10.0), and age less than 60 yr (OR=2.7, 95% CI: 1.0-7.1) were shown to be significant risk factors for developing post-ERCP pancreatitis. In patients who underwent pancreatography with or without cholangiography, the risk of pancreatitis was significantly lower in the indomethacin group compared with the control group (P=0.01, RRR=88%, ARR=0.16, NNT=6). Moderate to severe pancreatitis was significantly higher in the placebo group (P= 0.03). CONCLUSIONS This trial shows that rectal indomethacin given immediately before ERCP can reduce the incidence and severity of post-ERCP pancreatitis.
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Affiliation(s)
- Rasoul Sotoudehmanesh
- Digestive Diseases Research Center, Medical Sciences/University of Tehran, Tehran, Iran
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Abstract
Post-ERCP pancreatitis (PEP) is a potential complication of ERCP. Pharmacotherapy for prevention of PEP aims at reducing basal sphincter pressure and contractility or a decrease in pancreatic secretion to reduce intraductal pressure. Timing and route of administration of drugs are critical to ensure maximum benefits from medications. Pancreatic stenting offers an alternative to decompress the pancreas and is effective in reducing PEP in high-risk patients.
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Rochester JS, Jaffe DL. Minimizing complications in endoscopic retrograde cholangiopancreatography and sphincterotomy. Gastrointest Endosc Clin N Am 2007; 17:105-27, vii. [PMID: 17397779 DOI: 10.1016/j.giec.2006.11.002] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
Endoscopic retrograde cholangiopancreatography (ERCP) is a major tool in the diagnosis and management of numerous biliary and pancreatic conditions, including choledocholithiasis as well as benign and malignant pancreatic diseases, especially those causing biliary obstruction. Since the procedure's inception, the techniques and indications have evolved along with advances in technology and an improved understanding of risks associated with ERCP. The trend has been away from purely diagnostic procedures; most ERCPs are now therapeutic in intent. ERCP remains among the more invasive of endoscopic procedures, with significant rates of complications that can be major. As advances are made in less invasive technology, it is important to understand the complications of ERCP and how best to avoid them.
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Affiliation(s)
- Jeremy S Rochester
- Division of Gastroenterology, Montefiore Medical Center, Albert Einstein College of Medicine, 111 East 210th Street, Bronx, NY 10467-2490, USA
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