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.     

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.     

Prophylactic administration of somatostatin or gabexate does not prevent pancreatitis after ERCP: an updated meta-analysis

BACKGROUND: The prophylactic use of somatostatin or gabexate in patients undergoing ERCP is still controversial. OBJECTIVE: Our purpose was to update the meta-analysis on somatostatin (SS, 16 studies) or gabexate mesylate (GM, 9 studies) prophylaxis of post-ERCP pancreatitis and to run sensitivity analyses by subgrouping trials according to schedules of drug administration. MAIN OUTCOME MEASUREMENTS: Post-ERCP acute pancreatitis, hyperamylasemia, and pain. RESULTS: Heterogeneity was present among selected studies, which appeared eliminated when only 9 high-quality trials on SS and 5 randomized studies on GM were considered. After data were pooled from SS trials, pancreatitis occurred in 7.3% of controls versus 5.3% of treated patients, a nonsignificant effect (odds ratio [OR] = 0.73; 95% CI 0.54-1.006). The funnel plot showed asymmetry with a negative slope (P = .05). The meta-analysis produced negative results for either short- (<6 hours) or long-term (> or =12 hours) SS infusion, whereas a bolus injection proved effective (OR = 0.271; 95% CI 0.138-0.536), with a pooled absolute risk reduction of 8.2% (95% CI 4.4-12.0%). Postprocedural hyperamylasemia, but not pain, was significantly reduced (OR = 0.67, 95% CI 0.57-0.81). In controls and patients treated with GM, pancreatitis developed in 5.7% versus 4.8%, hyperamylasemia in 40.6% versus 36.9%, and pain in 1.7% versus 8.9%. All pooled ORs were nonsignificant: P = .34, .17, and .19, respectively. The meta-analysis produced no significant effect for either short-term (<6 hours) or long-term (>12 hours) GM administration. CONCLUSION: Short- or long-term infusion of SS or GM proved ineffective in reducing post-ERCP pancreatitis and pain. The beneficial effect of SS on postprocedural hyperamylasemia seems of marginal significance. When given as a bolus injection, SS maintains its promise in this field, but additional data are needed.     

Somatostatin and gabexate for post-endoscopic retrograde cholangiopancreatography pancreatitis prevention: meta-analysis of randomized placebo-controlled trials

BACKGROUND AND AIM: Prior studies have suggested the efficacy of somatostatin and gabexate in post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis prevention. We examined this notion in our study. METHODS: An extensive literature search led to the inclusion of seven homogeneous high-quality studies (Jadad score >or=4), involving 3,130 patients. The studies were grouped according to the drug's length of administration: given as an infusion for 12 h (groups SOM1 and GAB1 for somatostatin and gabexate, respectively); given as an infusion for less then 12 h (groups SOM2 and GAB2 for somatostatin and gabexate, respectively); and given as a bolus (group SOM3 for somatostatin, none identified for gabexate). Separate meta-analyses investigating post-procedural pancreatitis and hyperamylasemia rates were conducted in a random effects model. RESULTS: Pancreatitis analyses yielded significant risk differences for the SOM1, SOM3 and GAB1 groups. The resulting values were 7.7% (95% confidence intervals [CI][3.4 to 12.0], P < 0.0001), 8.2% (95% CI [4.4 to 12.0], P < 0.0001) and 5.2% (95% CI [1.1 to 9.4], P = 0.01), respectively. No statistically significant risk differences were observed for the SOM2 and GAB2 groups: -2.3% (95% CI [-5.2 to 0.5], P = 0.11) and -1.1% (95% CI [-3.8 to 1.6], P = 0.41), respectively. Hyperamylasemia analyses yielded significant risk differences for the SOM1 and SOM3 groups (P = 0.017 and 0.001, respectively), although not for the SOM2, GAB1 and GAB2 groups (P = 0.44, 0.49 and 0.47, respectively). CONCLUSIONS: Somatostatin administered as a bolus seems to be an efficacious measure of post-ERCP pancreatitis prevention, reducing pancreatitis and hyperamylasemia rates, and being applicable to clinical practice. Further study is required before its introduction into routine care.     

Gabexate or somatostatin administration before ERCP in patients at high risk for post-ERCP pancreatitis: a multicenter,placebo-controlled,randomized clinical trial

BACKGROUND: ERCP is frequently complicated by pancreatitis. The aims of this study were to assess the efficacy of somatostatin and gabexate for prevention of post-ERCP pancreatitis in high-risk patients and to determine predisposing factors for post-ERCP pancreatitis. A meta-analysis was conducted of all published studies on the use of somatostatin or gabexate for prevention of post-ERCP pancreatitis. METHODS: A double blind, multicenter, placebo-controlled trial was conducted in patients at high risk for post-ERCP pancreatitis. Patients were randomized to receive an intravenous infusion of somatostatin (750 mg), gabexate (500 mg), or placebo that was started 30 minutes before endoscopy and continued for 2 hours afterward. Patients were evaluated clinically and serum amylase levels determined at 4 and 24 hours after endoscopy. RESULTS: No significant difference in the occurrence of pancreatitis, hyperamylasemia, or abdominal pain was observed among placebo-, gabexate-, and somatostatin-treated patients. A sphincterotomy longer than 2 cm (p = 0.0001), more than 3 pancreatic injections (p = 0.0001), and unsuccessful cannulation (p = 0.008) were predictive of post-ERCP pancreatitis. Hyperamylasemia was predicted by more than 3 pancreatic injections (p = 0.0001) and sphincterotomy (p = 0.02). The meta-analysis of trials of short-term infusion of gabexate or somatostatin did not show efficacy for either drug. CONCLUSIONS: Short-term administration of gabexate or somatostatin in patients at high risk for pancreatitis is ineffective for prevention of ERCP-induced pancreatitis. Pancreatic injury is related to maneuvers used to obtain biliary access rather than to any patient characteristic or endoscopist experience.     

Ulinastatin shows preventive effect on post-endoscopic retrograde cholangiopancreatography pancreatitis in a multicenter prospective randomized study

BACKGROUND AND AIM: Endoscopic retrograde cholangiopancreatography (ERCP) is a useful diagnostic and therapeutic procedure; however, ERCP occasionally causes post-ERCP pancreatitis. The administration of gabexate mesilate has been reported to be effective for the prevention for post-ERCP pancreatitis when given during and after the procedure. The aim of the present study was to investigate the preventive effect of the novel protease inhibitor ulinastatin on post-ERCP pancreatitis. METHODS: One hundred and thirty-nine patients who underwent the ERCP procedure were studied. These patients were randomly divided into three groups based on the agent and dose given during and following the ERCP procedure: gabexate mesilate (900 mg), high-dose ulinastatin (450 000 units) and low-dose ulinastatin (150 000 units). Serum amylase, interleukin (IL)-6 and IL-8 levels and plasma polymorphonuclear leukocyte elastase (PMN-E) activity were measured after ERCP. In addition, post-ERCP hyperamylasemia and post-ERCP pancreatitis were recorded. RESULTS: There were no significant differences in serum amylase, IL-6 and IL-8 levels and PMN-E activity after ERCP procedure between the three groups. Post-ERCP pancreatitis was observed in two (4.3%), three (6.5%) and four (8.5%) cases in the gabexate mesilate, high-dose ulinastatin and low-dose ulinastatin groups, respectively. Multiple logistic regression analysis showed that the addition of endoscopic sphincterotomy during the ERCP procedure was the only significant risk factor for the development of post-ERCP hyperamylasemia and post-ERCP pancreatitis (P = 0.03 and P = 0.04, respectively), but there was no significant difference in the occurrence of post-ERCP hyperamylasemia and post-ERCP pancreatitis between the three groups receiving different preventative treatments. CONCLUSION: The administration of low- and high-dose ulinastatin has similar effects to high-dose gabexate in the prevention of post-ERCP pancreatitis.     

加贝酯在ERCP诊治术后的临床应用评价

目的观察加贝酯在预防ERCP术后引起的高淀粉酶血症和急性胰腺炎的有效性。方法两组行ERCP的病人,试验组应用加贝酯。观察试验组和对照组患者术后血清淀粉酶的变化。结果试验组术后高淀粉酶血症及急性胰腺炎发生率明显低于对照组(P<0.05)。结论加贝酯能有效预防ERCP术后高淀粉酶血症及急性胰腺炎的发生。     

联合应用质子泵抑制剂、生长抑素和加贝酯预防ERCP术后胰腺炎和高淀粉酶血症的临床研究

背景：急性胰腺炎和高淀粉酶血症是内镜逆行胰胆管造影术（ERCP）的主要并发症,术前用药对预防和减轻并发症的作用尚存争议。目的：探讨联合应用质子泵抑制剂、生长抑素和加贝酯对ERCP术后胰腺炎（PEP）和高淀粉酶血症的预防作用。方法：共纳入510例行ERCP的患者,随机分为加贝酯组、生长抑素组、联合治疗组（质子泵抑制剂＋生长抑素＋加贝酯）和安慰剂组。观察术后2h、12h和24h血清淀粉酶水平,评估PEP和高淀粉酶血症的发生率．并分析PEP和高淀粉酶血症的危险因素。结果：ERCP术后2h、12h、24h,联合治疗组、生长抑素组和加贝酯组血清淀粉酶水平显著低于安慰剂组（P〈0．05或P〈0．01）,联合治疗组血清淀粉酶水平亦显著低于生长抑素组或加贝酯组（P〈0．05）。ERCP胰管显影者的PEP和高淀粉酶血症发生率显著高于胆管显影者（P〈0．05）。单变量分析显示ERCP操作过程中胰管多次显影、导丝多次插入胰管、导丝辅助、反复插管以及操作中发生上腹疼痛为PEP和高淀粉酶血症的技术相关性高危因素。结论：ERCP术前后联合应用质子泵抑制剂、生长抑素和加贝酯可改善PEP和高淀粉酶血症的发生。     

加贝酯预防ERCP术后胰腺炎的临床研究

目的探讨加贝酯预防ERCP术后胰腺炎、胰性腹痛和高淀粉酶血症的疗效和安全性。方法按随机双盲法将拟行ERCP术的患者分为加贝酯组和对照组。加贝酯组患者在ERCP术前0．5h起开始静脉滴注加贝酯(300mg加入林格氏液500ml),维持4．5h。对照组则仅静脉滴注林格氏液500ml,也维持4．5h。结果共有94例患者完成研究,其中加贝酯组48例,对照组46例。加贝酯组有3例(6．3％)、对照组有9例(19．6％)患者发生了胰腺炎(P=0．040)；高淀粉酶血症的发生率两组分别为12例(25．0％)和21例(45．7％)(P=0．036)；胰性腹痛的发生率两组分别为5例(10．4％)和14例(30．4％)(P=0．016)。结论以加贝酯总量300mg持续4．5h静脉滴注(术前0．5h起给药)较安慰剂能有效减少ERCP术后胰腺炎发生率,减少高淀粉酶血症及胰性腹痛的发生。     

Efficacy of postprocedure administration of gabexate mesylate in the prevention of post-ERCP pancreatitis: a randomized, controlled, multicenter study

BACKGROUND AND OBJECTIVE: Gabexate mesylate reduces the incidence of post-ERCP pancreatitis. Patient-related risk factors associated with pancreatitis can be identified before ERCP, but the procedure-related factors are recognized only at the end of the procedure. This study's aim was to evaluate whether gabexate mesylate administered after ERCP reduces the incidence of pancreatitis. DESIGN: Randomized, prospective, double-blind, multicenter trial. SETTING: Tertiary care centers. PATIENTS AND INTERVENTION: A total of 608 patients undergoing ERCP were treated with gabexate mesylate 500 mg within 1 hour before ERCP (group A, 203 patients) or within 1 hour after ERCP (group B, 203), or with saline solution (group C, 202). MAIN OUTCOME MEASUREMENTS: The incidence and severity of pancreatitis and hyperamylasemia, as well as factors associated with the development of pancreatitis. RESULTS: The groups were similar for demographic characteristics, indications to ERCP, risk factors for pancreatitis, and therapeutic procedures. The incidence of pancreatitis was 3.9% in group A, 3.4% in group B, and 9.4% in group C (P<.01). Two patients (in groups A and C) developed necrotizing pancreatitis, and 1 died. Hyperamylasemia occurred in 23.6% in groups A and B, and in 24.7% in group C. Levels of amylase, the incidence of abdominal pain, and other complications occurred similarly. Female sex (odds ratios [OR] 2.7, 95% CI 1.2-5.9) and difficult cannulation (OR 5.6, 95% CI 2.6-12.3) were independently associated with pancreatitis. CONCLUSIONS: The administration of gabexate mesylate after ERCP protects against the development of pancreatitis similarly to the preprocedure administration. Factors associated with pancreatitis were mainly recognized after ERCP. We suggest administering gabexate mesylate after ERCP only in those patients recognized to be at risk of developing pancreatitis.     

Antisecretory vs. antiproteasic drugs in the prevention of post-ERCP pancreatitis: the evidence-based medicine derived from a meta-analysis study

Uncertainties still exist about the clinical benefit of pharmacological prevention of post-ERCP pancreatitis by either antisecretory drugs such as somatostatin and its long-acting analogue octreotide, or protease inhibitors such as gabexate mesilate. Recent, large-scale prospective studies have reported a fourfold reduction in acute pancreatitis as compared to a placebo with the prophylactic administration of either gabexate mesilate or somatostatin, whereas octreotide was found to be ineffective. An initial meta-analysis of all available controlled trials on this topic has confirmed these findings. The indiscriminate use of these drugs in all patients is unlikely to be cost-effective, but the selective use of prophylaxis for high-risk patients might be advocated. Moreover, inasmuch as 85% of complications developed within 4 to 6 hours of completing the ERCP, it would be reasonable to infuse drugs only for this limited length of time. A recent prospective trial, carried out on high-risk patients, has surprisingly documented a higher incidence, although a non-significant one, of pancreatitis in patients who received short-term prophylaxis with somatostatin or gabexate mesilate than those given a placebo: 11.5% and 8.1% vs. 6.5%, respectively. In order to explore this discrepancy, the original meta-analysis was updated by including data of this negative trial: heterogeneity among the trials was apparent. A careful scrutiny of the most recent studies has revealed differences in patient population, protocols of drug administration, technique and operator-related risk factors for complications among the trials, which could explain, by themselves, the contrasting results reported by the interventional studies. In conclusion, current literature does not support the prophylactic use of either somatostatin or gabexate mesilate for the prevention of ERCP-related pancreatic damage, even in patients deemed to be at high risk for complications. At present, post-ERCP complications (and pancreatitis) can be prevented efficaciously by appropriate selection of patients, mastering of the technique and operator competence.     

Comparison between ulinastatin and gabexate mesylate for the prevention of post-endoscopic retrograde cholangiopancreatography pancreatitis: a prospective,randomized trial

Background It has been reported that the administration of ulinastatin, gabexate mesylate, or somatostatin may be effective in the prevention of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis. However, few randomized trials of ulinastatin and gabexate mesylate for the prevention of post-ERCP pancreatitis have been reported. The aim of this study was to compare the efficacy of ulinastatin and gabexate mesylate for the prevention of post-ERCP pancreatitis. Methods Sixty-eight patients who underwent diagnostic ERCP at our hospital were divided at random by computer-generated randomization into an ulinastatin group (n = 34) and a gabexate group (n = 34). Each patient received a continuous intravenous infusion of ulinastatin (150 000 units) or gabexate mesylate (600 mg), beginning 60–90 min before the ERCP and continuing until 22 h after the ERCP. The primary endpoint was the incidence of post-ERCP pancreatitis, and the secondary endpoints were the incidences of hyperenzymemia and pain. Results The overall incidence of post-ERCP pancreatitis was 2.9% (two patients), comprising one patient in the ulinastatin group and one patient in the gabexate group (2.9% vs 2.9%, respectively). Neither of these two patients developed severe pancreatitis. There were no significant differences in the serum levels of pancreatic enzymes or in the levels of pain between the two groups. Conclusions There was no clinical difference between the effect of preventive administration of ulinastatin and that of gabexate mesylate on the incidence of post-ERCP pancreatitis. Ulinastatin may be equivalent in efficacy to gabexate for reducing the incidence 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.     

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.     

经内镜逆行胰胆管造影术后急性胰腺炎与高淀粉酶血症对比观察

目的 比较经内镜逆行胰胆管造影术(ERCP)后急性胰腺炎(PEP)与高淀粉酶血症(PEHA)患者的临床特点及影响因素,为预防病情进展提供依据。 方法 选取武汉大学人民医院2017年1月-2019年8月住院行ERCP的患者117例,所有患者术前均预防性使用双氯芬酸钠栓塞肛。术后发生PEHA组77例,PEP组40例,比较2组患者临床特点及影响因素。符合正态分布的计量资料2组间比较采用t检验;不符合正态分布的计量资料2组间比较采用Mann-Whitney U检验;计数资料2组间比较采用χ2检验;采用多因素logistic回归分析PEP的独立影响因素。结果 术前ALP(Z=-2.518,P=0.012)、GGT(Z=-2.313,P=0.021)、TBil(Z=-2.978,P=0.003)、DBil(Z=-3.069,P=0.002)水平及术中是否行导丝进入胰管检查(χ2=4.176,P=0.041)在两组之间差异显著。进一步logistic回归分析结果显示,导丝进入胰管次数≥3次[优势比(OR)=2.469,95%可信区间(95%CI): 1.199~5.188,P=0.047]、ALP<125 U/L(OR=5.499,95%CI: 1.452~18.830,P=0.012)、TBil<22 μmol/L(OR=4.249,95%CI: 1.023~17.648,P=0.046)是影响PEP发生的独立危险因素。结论 即使预防性使用双氯芬酸钠栓剂,术前ALP、TBil水平正常及术中导丝多次进入胰管的患者更易发生PEP,需引起手术医师警惕。根据病情,术前及术后采取早期干预措施可能减少PEHA向PEP进展,减少中重度PEP的发生,改善预后。     

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.     

Pharmacologic prophylaxis of post-endoscopic retrograde cholangiopancreatography pancreatitis: protease inhibitors and NSAIDs in a meta-analysis

Post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis is the most frequent complication of ERCP. Several meta-analyses have examined the effects of protease inhibitors (gabexate mesilate, ulinastatin, and nafamostat mesilate) and non-steroidal anti-inflammatory drugs (NSAIDs) on post-ERCP pancreatitis, but the results have been confusing. Since the previous meta-analysis, several new studies have been published on this topic. To provide an updated quantitative assessment of the effectiveness of protease inhibitors and NSAIDs in preventing post-ERCP pancreatitis, we conducted a meta-analysis of randomized trials for patients at risk of post-ERCP pancreatitis. Twenty-six articles were included in this meta-analysis. Nafamostat mesilate (summary RR = 0.41; 95 %CI 0.28–0.59; n = 4 studies) and NSAIDs (summary RR = 0.58; 95 %CI = 0.44–0.76; n = 7 studies) were associated with decreased risk of post-ERCP pancreatitis in the high-quality studies. However, gabexate mesilate (summary RR = 0.64; 95 %CI = 0.36–1.13; n = 6 studies) and ulinastatin (summary RR = 0.65; 95 %CI = 0.33–1.30; n = 2 studies) were not associated with decreased risk of post-ERCP pancreatitis in the high-quality studies. This is the first meta-analysis to compare the effects of three protease inhibitors. Solid evidence supports the use of nafamostat mesilate and NSAIDs for preventing post-ERCP pancreatitis.     

Indomethacin may reduce the incidence and severity of acute pancreatitis after ERCP

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.     

Prophylactic effect of somatostatin on post-ERCP pancreatitis: a randomized controlled trial

BACKGROUND: Somatostatin is a potent inhibitor of pancreatic secretion and has been studied for its prophylactic effect on post-ERCP pancreatitis. However, results of previous trials have been inconclusive. METHODS: A prospective double-blind controlled study was performed to evaluate the effectiveness of somatostatin in preventing post-ERCP pancreatitis. Post-ERCP enzyme elevation, abdominal pain and pancreatitis were evaluated and compared between 109 patients randomized to receive somatostatin infusion and 111 patients randomized to receive normal saline infusion (placebo); both started 30 minutes before ERCP and continued for 12 hours. RESULTS: Post-ERCP elevation of serum amylase and lipase levels at 6 and 24 hours after ERCP was less frequent in the group given somatostatin but not statistically significant. There was a tendency toward lower mean serum amylase and lipase levels at 24 hours in patients given somatostatin, although the difference was not statistically significant either. Eight patients given somatostatin (7%) and 18 patients given placebo (16%) had significant abdominal pain after ERCP requiring analgesia (p = 0.04). The frequency of clinical pancreatitis was significantly lower in patients given somatostatin (3%) than in those given placebo (10%) (p = 0.03). CONCLUSIONS: Prophylactic treatment with somatostatin reduced the frequency of post-ERCP pancreatitis.     

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.