Nifedipine for prevention of post-ERCP pancreatitis: a prospective,double-blind randomized study

BACKGROUND: Pancreatitis is the most common complication of ERCP. Calcium channel inhibitors have been shown to prevent the development of experimental pancreatitis. The aim of this randomized, placebo-controlled trial was to determine whether the calcium channel blocker nifedipine prevents post-ERCP pancreatitis. METHODS: Patients referred for ERCP were enrolled. Those being treated with a calcium channel inhibitor and those with acute or chronic pancreatitis were excluded. Nifedipine or placebo was administered orally less than 3 hours before and within 6 hours after ERCP. The main outcome measure was the number of cases of post-ERCP pancreatitis; a secondary outcome was the rate of post-ERCP pain (without pancreatitis) that persisted for 12 or more hours. RESULTS: One hundred fifty-five patients (70 women, 85 men; mean [SD] age 65.8 [18.2] years; range, 23-97 years) were enrolled and randomized to receive nifedipine (76 patients) or placebo (79 patients). The two groups were comparable. Procedures performed were retrograde diagnostic cholangiopancreatography alone (n = 33), biliary sphincterotomy (n = 31), stone extraction (n = 39), stent placement (n = 37), sphincteroplasty (n = 5), and other (n = 3). ERCP was unsuccessful in 5 patients. A single case of severe pancreatitis was observed (placebo group). The rate of post-ERCP pancreatitis was not different between groups (nifedipine, 10 patients, 13.2%; placebo, 14 patients, 17.7%; p = 0.4). The frequency of post-ERCP pain was not different between the groups. The only independent predictor of post-ERCP pancreatitis was difficult cannulation in both groups (OR = 3.78: 95% CI [1.25, 11.45]). CONCLUSION: This study failed to demonstrate a significant effect of nifedipine in the prevention of post-ERCP pancreatitis. A multicenter trial with greater statistical power would be needed to demonstrate a benefit for this drug.     

Guidewire cannulation reduces risk of post-ERCP pancreatitis and facilitates bile duct cannulation

OBJECTIVE: To evaluate if using a soft-tipped guidewire to cannulate the common bile duct may ameliorate development of post-ERCP pancreatitis and facilitate cannulation of the CBD. DESIGN AND SETTING: A single-center, blinded, randomized trial of conventional cannulation technique using sphinctertome and contrast injection versus guidewire cannulation technique. METHODS: We prospectively randomized 300 patients to conventional cannulation (group I) or guidewire cannulation (group II) technique. OUTCOME MEASURES: Primary outcome measure was incidence of acute pancreatitis and secondary outcome measures were ease of cannulation of common bile duct (assessed by attempts required for common bile duct cannulation & rates of precut sphincterotomy) and overall complication rates. RESULTS: Guidewire cannulation was associated with significantly lower likelihood of post-ERCP pancreatitis (adjusted OR 0.43, 95% CI 0.21-0.89, P= 0.02). Twenty-five patients (16.6%) in group I and thirteen patients (8.6%) in group II developed acute pancreatitis, P= 0.037. All instances of pancreatitis were mild. There were more women in group II; 41 in group I and 59 in group II, P= 0.028. Otherwise the two groups were comparable for age, age under 35 yr, indication for ERCP, diagnosis, and number of patients with SOD. The number of patients requiring 0-3, 4-6, and 7-10 attempts for successful cannulation of the common bile duct were 87, 48, and 15 in group I and 117, 24, and 9 in group II, respectively, P= 0.001. A total of 33 patients in group I and 13 patients in group II required precut sphincterotomy, P= 0.007. Rates of accidental pancreatic duct cannulation were 21 in group I and 27 in group II, P= 0.34. Rates of overall complication were not significantly different in the two groups. CONCLUSIONS: Guidewire technique for bile duct cannulation lowers likelihood of post-ERCP pancreatitis by facilitating cannulation and reducing need for precut sphincterotomy.     

Ulinastatin for pancreatitis after endoscopic retrograde cholangiopancreatography: a randomized, controlled trial.

BACKGROUND & AIMS: Pancreatitis remains the major complication of endoscopic retrograde cholangiopancreatography (ERCP), and hyperenzymemia after ERCP is common. Because ulinastatin, a protease inhibitor, has proved effective in the treatment of acute pancreatitis, the aim of this study was to assess the efficacy of ulinastatin for the prevention of post-ERCP pancreatitis and hyperenzymemia. METHODS: In a multicenter, randomized, double-blind, placebo-controlled trial, patients undergoing a first ERCP were randomized to receive ulinastatin (150,000 U) or placebo by intravenous infusion for 10 minutes starting immediately before ERCP. All patients were hospitalized at least 24 hours after ERCP for evaluation of clinical symptoms. Serum pancreatic enzyme levels were measured before and at 4 and 18 hours after ERCP. The primary end point was the incidence of post-ERCP pancreatitis and the secondary objective was the occurrence of hyperenzymemia. RESULTS: A total of 406 patients were enrolled (204 in the ulinastatin group and 202 in the placebo group). There were no differences between the 2 groups regarding baseline characteristics, details of fluoroscopic findings, or endoscopic procedure. The incidence of hyperenzymemia was significantly lower in the ulinastatin group than in the placebo group (amylase, P = .011; lipase, P = .008). Six patients in the ulinastatin group and 15 patients in the placebo group developed pancreatitis (2.9% vs. 7.4%, P = .041). There was no case of severe pancreatitis in either group. Patients who received ulinastatin did not present any side effects related to the medication. CONCLUSIONS: Prophylactic short-term administration of ulinastatin decreases the incidence of pancreatitis and hyperenzymemia after ERCP.     

Prophylaxis of ERCP-related pancreatitis: a randomized, controlled trial of somatostatin and gabexate mesylate.

BACKGROUND & AIMS: It still is debated whether post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis can be prevented by administering either somatostatin or gabexate mesylate. The aim of the study is to assess the efficacy of a 6.5-hour infusion of somatostatin or gabexate mesylate in preventing ERCP-related complications. METHODS: In a double-blind multicenter trial, 1127 patients undergoing ERCP were randomly assigned to intravenous administration of somatostatin (750 microg; n = 351), gabexate mesylate (500 mg; n = 381), or placebo (saline; n = 395). The drug infusion started 30 minutes before and continued for 6 hours after endoscopy. Patients were evaluated clinically, and serum amylase levels were determined at 4, 24, and 48 hours after endoscopy. RESULTS: No significant differences in incidences of pancreatitis, hyperamylasemia, or abdominal pain were observed among the placebo (4.8%, 32.6%, and 5.3%, respectively), somatostatin (6.3%, 26.8%, and 5.1%, respectively), and gabexate mesylate groups (5.8%, 31.5%, and 6.3%, respectively). Univariate analysis of patient characteristics and endoscopic maneuvers showed that a Freeman score >1 (P < 0.0001), >/=3 pancreatic injections (P < 0.00001), and precut sphincterotomy (P = 0.01) were significantly associated with post-ERCP pancreatitis. At multiple logistic regression analysis, >/=3 pancreatic injections (odds ratio [OR], 1.95; 95% confidence interval [CI], 1.45-2.63) and a Freeman score >1 (OR, 1.47; 95% CI, 1.11-1.94) retained their predictive power. CONCLUSIONS: Long-term (6.5-hr) administration of either somatostatin or gabexate mesylate is ineffective for the prevention of post-ERCP pancreatitis. Pancreatic injury seems to be related to difficulty in common bile duct access.     

Does prophylactic pancreatic stent placement reduce the risk of post-ERCP acute pancreatitis? A meta-analysis of controlled trials

BACKGROUND: Impaired drainage of the pancreatic duct is one of the possible triggers for post-ERCP acute pancreatitis. The aim of this meta-analysis was to determine whether temporary stent placement across the main pancreatic-duct orifice lowers the frequency of post-ERCP acute pancreatitis in patients at high risk for this complication. METHODS: Two reviewers systematically identified prospective studies that (1) compared the risk of post-ERCP acute pancreatitis in patients with pancreatic stent placement vs. no stent placement and (2) included patients at high risk of developing this complication. Studies were assessed for methodologic quality and variations in execution and design. Frequency and severity of post-ERCP acute pancreatitis were the primary outcomes evaluated. RESULTS: Five trials involving 481 patients were selected. Of the 481, 55 (11.4%) patients developed pancreatitis after ERCP. Patients in the no stent group had 3-fold higher odds of developing pancreatitis compared with the stent group (15.5% vs. 5.8%; OR 3.2: 95% CI[1.6, 6.4]). Number needed to treat analysis showed that one in every 10 patients (95% CI[6,18]) could be expected to benefit from pancreatic-duct stent placement. CONCLUSIONS: Prophylactic temporary stent placement across the main pancreatic-duct orifice reduces the risk of post-ERCP acute pancreatitis in patients at risk for developing this complication.     

Twenty-four hour prophylaxis with increased dosage of octreotide reduces the incidence of post-ERCP pancreatitis

BACKGROUND: Acute pancreatitis is a common complication of ERCP, occurring in up to 10% of cases. Chemoprevention of post-ERCP pancreatitis remains a debated issue. OBJECTIVE: This study evaluated whether increased dosage of octreotide, a potent inhibitor of pancreatic secretion, could reduce the incidence of post-ERCP pancreatitis. DESIGN: In a randomized, double-blind, placebo controlled trial, the effect of 500 microg octreotide, given 3 times daily subcutaneously starting 24 hours before the ERCP procedure, was compared with that of placebo in patients who underwent diagnostic and/or therapeutic ERCP. PATIENTS: A total of 202 patients were included in the trial. The 2 groups were similar in regards to age, sex, indications for treatment, underlying diseases, and types of therapeutic procedures. Patients were clinically evaluated, and serum amylase levels were determined before ERCP and at 6 to 8 hours thereafter. Standardized criteria were used to diagnose and to grade the severity of post-ERCP pancreatitis. RESULTS: The medication was discontinued because of an allergic reaction in 1 patient in the octreotide group. The incidence of post-ERCP pancreatitis was significantly lower in the octreotide group compared with the placebo group (2/10 [2%] vs 9/101 [8.9%], P = .03). All cases of acute pancreatitis were mild, except 2 (1 moderate and 1 severe) in the placebo group. CONCLUSIONS: The results of this trial support the use of 24-hour prophylaxis with high dose of octreotide in the prevention of post-ERCP pancreatitis.     

Effects of Medications on Post-Endoscopic Retrograde Cholangiopancreatography Pancreatitis

Background and Aims: Drug-induced pancreatitis accounts for about 2% of acute pancreatitis. The aim of this study is to determine whether propofol and other medications are associated with increased risk for post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis. Methods: A retrospective study was conducted at a single tertiary care hospital. All patients who underwent ERCP from 2001 to 2004 were included. Diagnosis of acute post-ERCP pancreatitis was based on a consensus definition. Results: A total of 506 patients underwent ERCP. The total incidence of post-ERCP pancreatitis was 7.1%. There was no significant difference in post-ERCP pancreatitis between patients who received propofol compared to patients who received midazolam and fentanyl (9.0 vs. 5.9%, p = 0.18). Patients receiving an angiotensin receptor blocker were approximately 4 times more likely to develop post-ERCP pancreatitis (OR = 4.1, 95% CI 1.6–10.9). Patients younger than 65 years and smokers also had higher risk of developing acute post-ERCP pancreatitis than those who were older than 65 years (OR = 3.9, 95% CI 1.7–9.1) and non-smokers (OR = 2.8, 95% CI 1.3–6.2). Conclusions: Propofol is a safe sedative drug for ERCP without additional risk of developing acute post-ERCP pancreatitis. Use of angiotensin receptor blockers, smoking and younger age are independent risk factors for post-ERCP pancreatitis.     

Indomethacin for post-endoscopic retrograde cholangiopancreatography pancreatitis prophylaxis:Is it the magic bullet?

Acute pancreatitis is a common complication of endoscopic retrograde cholangiopancreatography (ERCP). Pancreatic duct stent insertion after ERCP has been widely accepted as the standard of care for the prevention of this complication in high-risk patients. Unfortunately, the placement of pancreatic stents requires higher level of endoscopic expertise and is not always feasible due to anatomic considerations. Therefore, effective non-invasive pharmacologic prophylaxis remains appealing, particularly if it is inexpensive, easily administered, has a low risk side effect profile and is widely available. There have been multiple studies evaluating potential pharmacologic candidates for post-ERCP pancreatitis (PEP) prophylaxis, most of them yielding disappointing results. A recently published large, multi-center, randomized controlled trial reported that in high risk patients a single dose of rectal indomethacin administered immediately after the ERCP significantly decreased the incidence of PEP compare to placebo.     

Risk factors for post-ERCP pancreatitis: a prospective multicenter study

OBJECTIVES: Pancreatitis is the most common and serious complication of diagnostic and therapeutic ERCP. The aim of this study is to examine the potential patient- and procedure-related risk factors for post-ERCP pancreatitis in a prospective multicenter study. METHODS: A 160-variable database was prospectively collected by a defined protocol on patients undergoing diagnostic or therapeutic ERCP at 15 centers in the Midwest Pancreaticobiliary Group and participating in a randomized controlled study evaluating whether prophylactic corticosteroids will reduce the incidence of post-ERCP pancreatitis. Data were collected prior to the procedure, at the time of procedure, and 24-72 h after discharge. Post-ERCP pancreatitis was diagnosed and its severity graded according to consensus criteria. RESULTS: Of the 1,115 patients enrolled, diagnostic ERCP with or without sphincter of Oddi manometry (SOM) was performed in 536 (48.1%) and therapeutic ERCP in 579 (51.9%). Suspected sphincter of Oddi dysfunction (SOD) was the indication for the ERCP in 378 patients (33.9%). Pancreatitis developed in 168 patients (15.1%) and was graded mild in 112 (10%), moderate in 45 (4%), and severe in 11(1%). There was no difference in the incidence of pancreatitis or the frequency of investigated potential pancreatitis risk factors between the corticosteroid and placebo groups. By univariate analysis, the incidence of post-ERCP pancreatitis was significantly higher in 19 of 30 investigated variables. In the multivariate risk model, significant risk factors with adjusted odds ratios (OR) were: minor papilla sphincterotomy (OR: 3.8), suspected SOD (OR: 2.6), history of post-ERCP pancreatitis (OR: 2.0), age <60 yr (OR: 1.6), > or =2 contrast injections into the pancreatic duct (OR: 1.5), and trainee involvement (OR: 1.5). Female gender, history of recurrent idiopathic pancreatitis, pancreas divisum, SOM, difficult cannulation, and major papilla sphincterotomy (either biliary or pancreatic) were not multivariate risk factors for post-ERCP pancreatitis. CONCLUSION: This study emphasizes the role of patient factors (age, SOD, prior history of post-ERCP pancreatitis) and technical factors (number of PD injections, minor papilla sphincterotomy, and operator experience) as the determining high-risk predictors for post-ERCP pancreatitis.     

Sphincter of Oddi manometry does not predispose to post-ERCP acute pancreatitis

BACKGROUND: Sphincter of Oddi manometry is helpful in selecting patients with sphincter of Oddi dysfunction who will respond to sphincterotomy. However, studies have shown that sphincter of Oddi manometry is associated with a high risk of post-procedure pancreatitis. The primary objective of this study was to evaluate the safety of sphincter of Oddi manometry in patients with sphincter of 2Oddi dysfunction. The secondary objective was to determine the risk factors for post-ERCP pancreatitis in patients with sphincter of Oddi dysfunction. METHODS: Data were collected retrospectively for 268 patients who had elective ERCP performed at 3 tertiary care medical centers between 1996 and 2000. Consecutive patients with suspected sphincter of Oddi dysfunction formed the case group; the control group consisted of patients with bile duct stone. The case group was further subclassified into group A, patients who underwent sphincter of Oddi manometry followed by immediate ERCP, and group B, patients who had ERCP without manometry. The rate of post-ERCP acute pancreatitis was compared between case and control groups. RESULTS: Twenty-seven percent of patients in the case group with suspected sphincter of Oddi dysfunction developed acute pancreatitis compared with 3.2% of patients in the control group with bile duct stone (p<0.001). There was no significant difference in the rate of acute pancreatitis in patients with sphincter of Oddi dysfunction who underwent sphincter of Oddi manometry and ERCP compared with patients with sphincter of Oddi dysfunction who had ERCP without sphincter of Oddi manometry (odds ratio 0.72: 95% CI[0.08, 9.2]). Multivariable logistic regression analysis showed that biliary sphincterotomy (p=0.006) and pancreatography (p=0.03) were independent predictors of acute pancreatitis. CONCLUSIONS: Patients with suspected sphincter of Oddi dysfunction are at higher risk of post-ERCP acute pancreatitis. Sphincter of Oddi manometry by itself does not appear to predispose to this complication.     

Does a pancreatic duct stent prevent post-ERCP pancreatitis? A prospective randomized study

BACKGROUND: Pancreatitis is the most frequent complication of ERCP. Injury to the papilla during ERCP could obstruct pancreatic duct outflow and initiate pancreatitis. A randomized prospective study was performed to evaluate the effect of pancreatic duct stent placement on the frequency and severity of post-ERCP pancreatitis in a selected group of patients. METHODS: The study group consisted of patients over 18 years of age at high risk for post-ERCP pancreatitis because of a difficult cannulation, sphincter of Oddi manometry, and/or the performance of endoscopic sphincterotomy. Patients were prospectively randomized to have a pancreatic duct stent placed or no stent upon completion of the ERCP. The endoprosthesis used was either a 5F nasopancreatic catheter or 5F, 2-cm long pancreatic stent. Study endpoints were the frequency and severity of post-ERCP pancreatitis. RESULTS: Patients undergoing pancreatic duct stent placement had a lower frequency of post-ERCP pancreatitis as compared with those in the control group (28% vs. 5%; p < 0.05). Pancreatitis tended to be less severe in patients who had pancreatic duct drainage. CONCLUSIONS: Pancreatic duct stent insertion after ERCP reduces the frequency of post-ERCP pancreatitis in patients at high risk for this complication.     

Intravenous bolus somatostatin after diagnostic cholangiopancreatography reduces the incidence of pancreatitis associated with therapeutic endoscopic retrograde cholangiopancreatography procedures: a randomised controlled trial

BACKGROUND: Previous studies suggested that somatostatin given before endoscopic retrograde cholangiopancreatography (ERCP) may reduce the incidence of post-ERCP pancreatitis. However, the routine use of somatostatin in all patients undergoing ERCP is not likely to be cost effective. This study evaluated whether intravenous bolus somatostatin given after diagnostic cholangiopancreatography could reduce the incidence of pancreatitis in a group of patients undergoing therapeutic ERCP procedures. METHODS: In a randomised, double blind, controlled trial, the effect of intravenous bolus somatostatin 250 microg given immediately after diagnostic cholangiopancreatography was compared with that of placebo in patients who required endoscopic sphincterotomy or other therapeutic procedures. The primary end point was the incidence of post-ERCP clinical pancreatitis, and a secondary end point was the incidence of hyperamylasemia. RESULTS: A total of 270 patients were randomised. The somatostatin group (n=135) and the placebo group (n=135) were comparable in age, sex, indications for treatment, and types of procedure. The frequencies of clinical pancreatitis (4.4% v 13.3%; p=0.010) and hyperamylasemia (26.0% v 38.5%; p=0.036) were both significantly lower in the somatostatin group compared with the placebo group. CONCLUSIONS: A single dose of intravenous bolus somatostatin, given immediately after diagnostic cholangiopancreatography, is effective in reducing the incidence of pancreatitis after therapeutic ERCP. This novel approach of administering prophylactic somatostatin may offer a cost effective prophylaxis for post-ERCP pancreatitis.     

Systematic review and meta-analysis on the prophylactic role of non-steroidal anti-inflammatory drugs to prevent post-endoscopic retrograde cholangiopancreatography pancreatitis

AIM: To critically appraise the published randomized, controlled trials on the prophylactic effectiveness of the non-steroidal anti-inflammatory drugs(NSAIDs), in reducing the risk of post-endoscopic retrograde cholangiopancreatography(ERCP) pancreatitis. METHODS: A systematic literature search(MEDLINE, Embase and the Cochrane Library, from inception of the databases until May 2015) was conducted to identify randomized, clinical trials investigating the role of NSAIDs in reducing the risk of post-ERCP pancreatitis. Random effects model of the meta-analysis was carried out, and results were presented as odds ratios(OR) with corresponding 95%CI.RESULTS: Thirteen randomized controlled trials on 3378 patients were included in the final meta-analysis. There were 1718 patients in the NSAIDs group and 1660 patients in non-NSAIDs group undergoing ERCP. The use of NSAIDs(through rectal route or intramuscular route) was associated with the reduced risk of post-ERCP pancreatitis [OR, 0.52(0.38-0.72), P = 0.0001]. The use of pre-procedure NSAIDs was effective in reducing approximately 48% incidence of post-ERCP pancreatitis, number needed to treat were 16 with absolute risk reduction of 0.05. But the risk of post-ERCP pancreattis was reduced by 55% if NSAIDs were administered after procedure. Similarly, diclofenac was more effective(55%) prophylactic agent compared to indomethacin(41%).CONCLUSION: NSAIDs seem to have clinically proven advantage of reducing the risk of post-ERCP pancreatitis.     

Can somatostatin prevent post‐ERCP pancreatitis? Results of a randomized controlled trial

BACKGROUND: Acute pancreatitis is the most common complication of endoscopic retrograde cholangiopancreatography (ERCP), occurring in 1-10% of patients. Several substances have been used, with negative results, in an attempt to prevent this complication. METHODS: We performed a double-blind randomized trial in 372 consecutive patients undergoing diagnostic or therapeutic ERCP to evaluate the role of somatostatin in preventing post-ERCP pancreatitis. The first group received continuous somatostatin infusion for 12 h starting 30 min before ERCP, the second group received a bolus intravenous injection of somatostatin at the time of cannulation of the papilla, and the third group received a placebo. RESULTS: Two patients in each of the somatostatin groups (1.7%) and 12 patients in the placebo group (9.8%) developed pancreatitis (P<0.05). Serum amylase levels 5 and 24 h after the procedure were lower in both groups that received somatostatin than in the placebo group (P<0.05). CONCLUSION: Somatostatin is useful in preventing post-ERCP pancreatitis. Further studies must be designed to investigate the cost-effectiveness of the drug and to determine the ideal administration route and dosage.     

A prospective, randomized, placebo-controlled trial of transdermal glyceryl trinitrate in ERCP: effects on technical success and post-ERCP pancreatitis

BACKGROUND: Despite the recent improvement in techniques and patient selection, post-ERCP pancreatitis remains the most frequent and dreaded complication of ERCP. Recent studies suggest that pretreatment with glyceryl trinitrate (GTN) may prevent post-ERCP pancreatitis and improve cannulation success. OBJECTIVE: To evaluate the effect of transdermal GTN on ERCP cannulation success and post-ERCP pancreatitis. DESIGN: Prospective, double-blind, placebo-controlled trial. SETTING: Tertiary referral university hospital. PATIENTS: A total of 318 patients (mean age 62 years, 61% women) were randomized to either active (n = 155) or placebo (n = 163) arms. INTERVENTIONS: Active patch (GTN) versus placebo patch. MAIN OUTCOME MEASUREMENTS: Cannulation time and success. Post-ERCP pancreatitis rates. RESULTS: There was no significant difference between the active or placebo arms for the following: successful initial cannulation (96.8% vs 98.8%), deep cannulation (96.1% vs 98.8%), time to successful cannulation, use of guidewire (27% vs 25%) or needle knife (13% vs 13%), and post-ERCP pancreatitis (7.4% of placebo patients and 7.7% active patients). Multivariate analysis identified women, younger patients, pancreatogram, number of attempts on papilla, and poor pancreatic-duct emptying after opacification as risk factors for post-ERCP pancreatitis. Transdermal GTN did not reduce post-ERCP pancreatitis in any of the identified high-risk groups. CONCLUSIONS: Transdermal GTN did not improve the rate of success in ERCP cannulation or prevent post-ERCP pancreatitis in either average or high-risk patient groups.     

吲哚美辛对内镜下逆行性胰胆管造影术后胰腺炎的预防

目的 探讨吲哚美辛对内镜下逆行性胰胆管造影术后胰腺炎(PEP)的预防作用.方法 从需行内镜下十二指肠乳头括约肌切开术(EST)的患者中选择年龄18～75岁,未合并有心、肺、肝、肾疾病及凝血功能障碍等手术高危因素,未合并恶性疾病,无非甾体类抗炎(NSAIDs)药物禁忌证,术前影像学及血清学证实未合并胰腺炎者.采用前瞻性随机对照病例研究方法分为吲哚美辛组和对照组.吲哚美辛组患者术后0.5h使用吲哚美辛100 mg肛塞,对照组给予安慰剂.以术后出现持续性的胰腺炎相关临床症状伴有术后24h血清淀粉酶值超过正常上限3倍、需住院1d以上者诊断为PEP.并对诊断PEP的患者于术后72 h进行APACHEⅡ评分.结果 2004年至2010年共入选348例患者,其中吲哚美辛组182例,对照组166例.吲哚美辛组术后发生PEP 6例(3.3％),对照组14例(8.4％),两组差异具有统计学意义(P＜0.05).吲哚美辛组发生PEP者的APACHEⅡ评分为4.3±1.3,对照组为7.4±1.7,两组差异具有统计学意义(P＜0.05).但两组高胰淀粉酶血症的发生率无统计学差异(9.3％比10.8％,P＞0.05).结论 内镜下乳头括约肌切开取石术后使用吲哚美辛肛栓预防术后胰腺炎是有效的,同时可以降低胰腺炎的严重程度.     

Post-ERCP pancreatitis

Pancreatitis remains the most common severe complication of endoscopic retrograde cholangiopancreatography (ERCP). Detailed information about the findings of previous studies concerning post-ERCP pancreatitis has not been utilized sufficiently. The purpose of the present article was to present guidelines for the diagnostic criteria of post-ERCP pancreatitis, and its incidence, risk factors, and prophylactic procedures that are supported by evidence. To achieve this purpose, a critical examination was made of the articles on post-ERCP pancreatitis, based on the data obtained by research studies published up to 2009. At present, there are no standardized diagnostic criteria for post-ERCP pancreatitis. It is appropriate that post-ERCP pancreatitis is defined as acute pancreatitis that has developed following ERCP, and its diagnosis and severity assessment should be made according to the diagnostic criteria and severity assessment of the Japanese Ministry of Health, Labour and Welfare. The incidence of acute pancreatitis associated with diagnostic and therapeutic ERCP is 0.4–1.5 and 1.6–5.4%, respectively. Endoscopic papillary balloon dilation is associated with a high risk of acute pancreatitis compared with endoscopic sphincterotomy. It was made clear that important risk factors include dysfunction of the Oddi sphincter, being of the female sex, past history of post-ERCP pancreatitis, and performance of pancreaticography. Temporary prophylactic placement of pancreatic stents in the high-risk group is useful for the prevention of post-ERCP pancreatitis [odds ratio (OR) 3.2, 95% confidence interval (CI) 1.6–6.4, number needed to treat (NNT) 10]. Use of nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with a reduction in the development of post-ERCP pancreatitis (OR 0.46, 95% CI 0.32–0.65). Single rectal administration of NSAIDs is useful for the prevention of post-ERCP pancreatitis [relative risk (RR) 0.36, 95% CI 0.22–0.60, NNT 15] and decreases the development of pancreatitis in both the low-risk group (RR 0.29, 95% CI 0.12–0.71) and the high-risk group (RR 0.40, 95% CI 0.23–0.72) of post-ERCP pancreatitis. As for somatostatin, a bolus injection may be most useful compared with short- or long-term infusion (OR 0.271, 95% CI 0.138–0.536, risk difference 8.2%, 95% CI 4.4–12.0%). The usefulness of gabexate mesilate was not apparent in any of the following conditions: acute pancreatitis (control 5.7 vs. 4.8% for gabexate mesilate), hyperamylasemia (40.6 vs. 36.9%), and abdominal pain (1.7 vs. 8.9%). Formulation of diagnostic criteria for post-ERCP pancreatitis is needed. Temporary prophylactic placement of pancreatic stents in the high-risk group offers the most promise as a means of preventing post-ERCP pancreatitis. As for pharmacological attempts, there are high expectations concerning NSAIDs because they are excellent in terms of cost-effectiveness, ease of use, and safety. There was no evidence of effective prophylaxis with the use of protease inhibitors, especially gabexate mesilate.     

Pretreatment With Methylprednisolone to Prevent Ercp-Induced Pancreatitis: A Randomized, Multicenter, Placebo-Controlled Clinical Trial

Objective: Pancreatitis remains the major complication of endoscopic retrograde cholangiopancreatography (ERCP). Uncontrolled data suggest a lower incidence of pancreatitis in patients with a history of iodine sensitivity when given pretreatment with corticosteroids. We conducted a clinical trial to assess the efficacy of a commonly prescribed corticosteroid, methylprednisolone, to prevent ERCP-induced pancreatitis.
Methods: Patients were entered into a randomized, multicenter, double-blind, placebo-controlled study of intravenous methylprednisolone (125 mg) versus a saline placebo immediately before the ERCP. All patients were evaluated for early and late complications.
Results: Two hundred eighty-six patients were randomized. Thirty-one randomized patients were excluded for technical reasons at the time of ERCP. Overall, the incidence of pancreatitis was 16 of 129 (12.4%, 95% CI: 6.7–18.1%) in the methylprednisolone group and 11 of 126 (8.7%, 95% CI: 4.4–15.1%) in the placebo group, which was not significantly different (   p = 0.34  ). Although there was a higher rate of sphincterotomy performed in the methylprednisolone group compared to the control group (  31.8% vs 16.8%, p = 0.005  ), the incidence of pancreatitis was not different when patients undergoing sphincterotomy were analyzed separately (13.6% in the methylprednisolone group and 9.6% in the placebo group,   p = 0.50  ). There was no significant difference between the two groups for those with ERCP-induced pancreatitis in hospital length of stay (   p = 0.22  ), days of parenteral analgesia (   p = 0.09  ), or days of parenteral nutrition (   p = 0.15  ).
Conclusion: Intravenous methylprednisolone is not beneficial in preventing ERCP-induced pancreatitis.     

High-dose allopurinol for prevention of post-ERCP pancreatitis: a prospective randomized double-blind controlled trial

BACKGROUND: Pancreatitis is the most common major complication of diagnostic and therapeutic ERCP. Allopurinol, a xanthine oxidase inhibitor that blocks generation of oxygen-derived free radicals, potentially may prevent post-ERCP pancreatitis. This study assessed the efficacy of high-dose oral allopurinol for prevention of post-ERCP pancreatitis. METHODS: A prospective, double-blind, placebo-controlled trial was conducted in 250 patients undergoing ERCP. Patients were randomized to receive allopurinol (600 mg) or placebo orally at 15 and 3 hours before the procedure. Patients were clinically evaluated, and serum amylase levels were determined before ERCP and at 6 and 24 hours thereafter. Standardized criteria were used to diagnose and to grade the severity of post-ERCP pancreatitis. RESULTS: A total of 243 patients were included in the analysis. The two groups were similar with regard to age; gender; underlying disease; indication for treatment; ERCP findings; and type of treatment, except for biliary sphincterotomy. Only 43 patients in the allopurinol group underwent biliary sphincterotomy vs. 87 in the placebo group ( p < 0.001). The frequency of acute pancreatitis was significantly lower in the allopurinol vs. the placebo group in the final multinomial regression analysis: allopurinol group, 4/125 (3.2%), with all 4 cases graded as mild, vs. placebo group, 21/118 (17.8%), of which 8/118 (6.8%) were graded as mild, 11/118 (9.3%) as moderate, and 2/118 (1.6%) as severe with fatal outcome ( p < 0.001). The protective effect of allopurinol was also apparent in the diagnostic ERCP and the biliary sphincterotomy subgroups when the frequency of post-ERCP pancreatitis was analyzed after stratification by procedure. The mean duration of hospitalization for pancreatitis was significantly shorter in the allopurinol compared with the placebo group (2.5 vs. 5.67 days; p < 0.001). CONCLUSIONS: Pretreatment with high-dose, orally administered allopurinol decreases the frequency of post-ERCP pancreatitis. Despite the promising results of this prospective, randomized trial, further studies are needed to verify these observations before allopurinol can be recommended for routine clinical use.     

吲哚美辛在预防ERCP术后胰腺炎中作用的研究

目的观察直肠应用吲哚美辛对ERCP术后胰腺炎（PEP）及高淀粉酶血症的预防作用。方法将行ERCP检查的168例患者随机分为两组,吲哚美辛组在ERCP术前30 min直肠内给予吲哚美辛栓剂100 mg,对照组在ERCP术前30 min直肠内给予安慰剂栓。ERCP术后观察患者有无腹痛,并于术后12 h做血清及尿淀粉酶测定。结果吲哚美辛组PEP发生率（6.0%）与安慰剂组PEP发生率（10.6%）无显著差异（P=0.28）,但是吲哚美辛组ERCP术后高淀粉酶血症的发生率（18.1%）显著低于安慰剂组（37.6%,P=0.005）。结论直肠应用吲哚美辛可以预防ERCP术后高淀粉酶血症的发生。