小剂量加贝酯预防ERCP术后胰腺炎及高淀粉酶血症的临床研究

目的 探讨小荆量加贝酯术前应用对内镜逆行胰胆管造影（ERCP）术后胰腺炎、高淀粉酶血症及其它并发症的预防作用。方法2005-03／2005-09我科进行ERCP术的63例病人，随机分为加贝酯组和安慰剂组，比较两组术后急性胰腺炎、高淀粉酶血症及其它并发症发生率的差异。结果 加贝酯组和安慰剂组胰腺炎发生率分别为7．41％和2．78％；术后高淀粉酶血症的发生率，矿别为55．56％和41．67％；两组间无显著差异；其它并发症如腹痛、腹胀、恶心、呕吐、出血等在两组间的发生率亦无显著差异。结论 ERCP术前应用小剂量加贝酯不能减轻术后高淀粉酶血症，也不能预防术后胰腺炎及其它并发症的发生。     

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。     

国产加贝酯预防ERCP术后胰腺炎的临床研究

目的探讨国产加贝酯预防ERCP术后胰腺炎、高淀粉酶血症和腹痛的疗效和安全性。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30～90min起开始静脉滴注加贝酯至术后12h为止，总剂量为1000mg。对照组仅静脉常规补液。结果共有77例患者完成研究，其中加贝酯组39例，对照组38例。加贝酯组有2例（5％）、对照组有8例（21％）患者发生了胰腺炎（P=0．038）；高淀粉酶血症的发生率两组分别为9例（23％）和18例（47％）（P=0．013）；腹痛的发生率两组分别为9例（23％）和13例（34％）（P=0．280）。结论加贝酯持续静脉滴注能有效减少ERCP术后胰腺炎发生率，减少高淀粉酶血症的发生。     

加贝酯预防内镜逆行胰胆管造影术后胰腺炎的实验研究

背景：急性胰腺炎是内镜逆行胰胆管造影术（ERCP）的常见并发症，加贝酯对ERCP术后胰腺炎的预防作用仍存在争议。目的：探讨加贝酯对大鼠ERCP术后胰腺炎的预防作用。方法：通过血压计传导50mmHg（1mmHg=0.133kPa）的恒定压力，向胰胆管内注入30％泛影葡胺，以制备SD大鼠ERCP术后胰腺炎模型。检测各组血清淀粉酶水平，并行胰腺组织病理学检查。结果：加贝酯治疗组的血清淀粉酶水平和胰腺组织炎症评分均显著低于胰腺炎对照组（P〈0.05）。结论：加贝酯静脉滴注对预防ERCP术后胰腺炎有效。     

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0.5 h起开始静脉滴注加贝酯(300 mg加入林格氏液500 ml),维持4.5 h.对照组则仅静脉滴注林格氏液500 ml,也维持4.5 h.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300 mg持续4.5 h静脉滴注(术前0.5 h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.     

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。     

加贝酯预防ERCP术后胰腺炎及高淀粉酶血症的临床分析

内镜逆行胰胆管造影术(ERCP)是肝胆胰疾病诊治的重要手段之一,目前广泛应用于临床.术后胰腺炎及高淀粉酶血症是ERCP最常见的并发症,其中术后胰腺炎可导致重症胰腺炎,甚至发生死亡[1].目前有多种药物被用于预防ERCP术后胰腺炎的发生,如抑肽酶、胰高血糖素、硝苯地平、奥曲肽[2-5]等,但是效果均不理想.本研究旨在探讨加贝酯对ERCP术后胰腺炎及高淀粉酶血症发生的预防作用.     

加贝酯预防ERCP术后胰腺炎临床研究

选择因各种胰腺胆管疾病接受ERCP治疗的患者100例,随机分为两组,治疗组ERCP术前30min给予加贝酯治疗,对照组ERCP术前、术后均不予加贝酯治疗。发现治疗组ERCP术后血淀粉酶一过性升高者19例,并发急性胰腺炎1例。对照组分别为32、15例。认为加贝酯能有效降低Oddi括约肌收缩频率和幅度,松驰括约肌,有利于提高造影导管插管的方便性和成功率,有利于预防ERCP术后胰腺炎的发生。     

ERBD预防ERCP术后高淀粉酶血症及胰腺炎临床分析

目的探讨内镜鼻胆管引流术（ENBD）预防内镜逆行胰胆管造影（ERCP）术后高淀粉酶血症及胰腺炎的临床疗效。方法胆石症行ERCP术患者160例,随机分为观察组85例和对照组65例,观察组术后置鼻胆管引流,对照组术后静脉滴注5％GS500ml＋法莫替丁20mg／d。分别于术前、术后3h、24h抽血,检测血淀粉酶（AMY）水平。结果两组术后3、24h血AMY明显高于术前;观察组术后3、24h血AMY明显低于对照组（P均〈0．05）;观察组发生高淀粉酶血症（AMY〉420U／L）2例,无胰腺炎发生,对照组发生高淀粉酶血症9例,急性胰腺炎5例。结论ERBD对ERCP术后预防高淀粉酶及胰腺炎有一定的临床价值。     

口服硫酸镁对ERCP术后胰腺炎发生和血淀粉酶水平的影响

目的:探讨口服硫酸镁对预防经内镜逆行胰胆管造影术(encoscopic retrograde cholangio-pancreatography,ERCP)后胰腺炎发生和血淀粉酶水平的影响.方法:将120例拟行ERCP的胆总管结石患者随机分为观察组和对照组各60例,观察组ERCP前30min口服50%硫酸镁100mL,对照组不予硫酸镁,观察两组术前及术后3、24h血清淀粉酶水平及术后高淀粉酶血症和胰腺炎发生情况.结果:两组患者术前血清淀粉酶水平的差异无统计学意义(P>0.05),观察组术后3、24h血清淀粉酶水平均显著低于对照组3、24h血清淀粉酶水平(P<0.05).观察组ERCP术后的高淀粉酶血症和胰腺炎发生率均分别显著低于对照组(P<0.05).结论:口服硫酸镁在一定程度上可降低ERCP术后血清淀粉酶水平,对预防ERCP术后高淀粉酶血症及胰腺炎可能有一定积极作用,当需大样本证实.     

Pharmacologic treatment can prevent pancreatic injury after ERCP: a meta-analysis

BACKGROUND: The identification of therapeutic agents that can prevent the pancreatic injury after endoscopic retrograde cholangiopancreatography (ERCP) is of considerable importance. METHODS: We performed a meta-analysis including 28 clinical trials on the use of somatostatin (12 studies), octreotide (10 studies), and gabexate mesilate (6 studies) after ERCP. Outcome measures evaluated were the incidence of acute pancreatitis, hyperamylasemia, and pancreatic pain. Three analyses were run separately: for all available studies, for randomized trials only, and for only those studies published as complete reports. RESULTS: When all available studies were analyzed, somatostatin and gabexate mesilate were significantly associated with improvements in all three outcomes. Odds ratios (OR) for gabexate mesilate were 0.27 (95% CI [0.13, 0. 57], p = 0.001) for acute pancreatitis, 0.66 (95% CI [0.48, -0.89], p = 0.007) for hyperamylasemia, and 0.33 (95% CI [0.18, 0.58], p = 0. 0005) for post-procedural pain. Somatostatin reduced acute pancreatitis (OR 0.38: 95% CI [0.22, 0.65], p < 0.001), pain (OR 0. 24: 95% CI [0.14, 0.42], p < 0.001), and hyperamylasemia (OR 0.65: 95% CI [0.48, 0.90], p = 0.008). Octreotide was associated only with a reduced risk of post-ERCP hyperamylasemia (OR 0.51: 95% CI [0.31, 0.83], p = 0.007) but had no effect on acute pancreatitis and pain. The statistical significance of data did not change after analyzing randomized trials only or studies published as complete reports. For each considered outcome, the publication bias assessment and the number of patients that need to be treated to prevent one adverse effect were, respectively, higher and lower for somatostatin than for gabexate mesilate. CONCLUSIONS: The pancreatic injury after ERCP can be prevented with the administration of either somatostatin or gabexate mesilate, but the former agent is more cost-effective. Additional studies comparing the efficacy of short-term infusion of somatostatin versus gabexate mesilate in patients at high risk for post-ERCP complications seem warranted.     

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.     

Multicentre comparative study of two schedules of gabexate mesilate in the treatment of acute pancreatitis. Italian Acute Pancreatitis Study Group.

AIM: To compare the efficacy of two different schedules of gabexate mesilate (900 mg/day, or 1,500 mg/day) in the treatment of severe acute pancreatitis. SETTING: Forty-two Italian medical and surgical centres took part in the study. STUDY DESIGN: A multicentre, prospective, open label, comparative, parallel-group, randomized study. METHODS: The patients enrolled in the study had acute pancreatitis as demonstrated by typical abdominal pain and baseline serum amylase concentrations more than twice the upper normal limit, findings compatible with acute pancreatitis at imaging techniques, and a Glasgow criteria score of > or =3. Patients were randomly assigned to one of the two schedules of treatment with gabexate mesilate being administered intravenously for at least 7 days. The minimum clinically relevant difference (delta), between groups, in incidence of complications due to acute pancreatitis, during the first month of the study treatment, was predefined as equal to 10%. RESULTS: A total of 199 patients were assigned to gabexate mesilate 900 treatment and 189 to gabexate mesilate 1,500. Complications developed in 88 patients within one month of beginning treatment 44/199: patients (22.1%) in the gabexate mesilate 900 group and 44/189 patients (23.3%) in the gabexate mesilate 1,500 group (difference 1.2%; 95% confidence interval: -7.2; 9.5%). CONCLUSIONS: Gabexate mesilate 900 mg per day is as effective as gabexate mesilate 1,500 mg per day in reducing the complications due to acute pancreatitis.     

Multicentre comparative study of two schedules of gabexate mesilate in the treatment of acute pancreatitis

Aim. To compare the efficacy of two different schedules of gabexate mesilate (900 mg/day, or 1, 500 mg/day) in the treatment of severe acute pancreatitis.Setting. Forty-two Italian medical and surgical centres took part in the study.Study design. A multicentre, prospective, open label, comparative, parallel-group, randomized study.Methods. The patients enrolled in the study had acute pancreatitis as demonstrated by typical abdominal pain and baseline serum amylase concentrations more than twice the upper normal limit, findings compatible with acute pancreatitis at imaging techniques, and a Glasgow criteria score of ≥3. Patients were randomly assigned to one of the two schedules of treatment with gabexate mesilate being administered intravenously for at least 7 days. The minimum clinically relevant difference (delta), between groups, in incidence of complications due to acute pancreatitis, during the first month of the study treatment, was predefined as equal to 10%.Results. A total of 199 patients were assigned to gabexate mesilate 900 treatment and 189 to gabexate mesilate 1,500. Complications developed in 88 patients within one month of beginning treatment 44/199: patients (22.1%) in the gabexate mesilate 900 group and 44/189 patients (23.3%) in the gabexate mesilate 1, 500 group (difference 1.2%; 95% confidence interval: −7.2; 9.5%).Conclusions. Gabexate mesilate 900 mg per day is as effective as gabexate mesilate 1500 mg per day in reducing the complications due to acute pancreatitis.     

Gabexate mesilate in the treatment of acute pancreatitis. Results of a Hannover multicenter double-blind study with 50 patients

We investigated the effect of a new synthetic protease- and phospholipase A2-inhibitor gabexate mesilate (FOY) in a multicenter (6 hospitals in Hannover and vicinity) double-blind study on the clinical course of acute pancreatitis. 50 patients were randomized into two subgroups. One group was treated with 3 X 300 mgs of gabexate mesilate per day for 9 days as a continuous intravenous infusion, the control group received placebo. There was no difference in these two groups regarding age and sex, but there was a discrepancy concerning the severity (stage I-IV) of the acute pancreatitis at the onset of treatment. More of the patients in the gabexate mesilate-group had severe disease on admission to hospital. Of the 7 patients (14%) who died, 5 were in the gabexate mesilate-group whereas only 2 were in the placebo group. This difference in the mortality rate is not significant. There was, however, a significant difference at the 5% level between the verum-group and the control group concerning the decline in alpha-amylase activity in serum and the number of complications. The difference was greatest in alcohol induced acute pancreatitis. A non-parametric test showed a significant reduction in hospitalisation time in the gabexate mesilate-group. Due to the small number of patients and the inhomogeneous clinical course of the acute pancreatitis a definite conclusion concerning the effect of gabexate mesilate on the clinical course of acute pancreatitis is not possible. Further studies with a much greater number of patients and more homogeneous groups with respect to the severity of the acute pancreatitis at the onset of the therapy with gabexate mesilate or placebo are necessary.     

Therapeutic regimens in acute experimental hemorrhagic pancreatitis. Effects of hydration, oxygenation, peritoneal lavage, and a potent protease inhibitor

In this study we evaluated the effects of hydration, oxygenation, peritoneal lavage, and the protease inhibitor gabexate mesilate in acute hemorrhagic pancreatitis induced by feeding mice a choline-deficient, ethionine-supplemented diet. Different groups of mice were kept at various concentrations of O2 (21%, 35%, and 45% O2), or were treated by either s.c. injections or i.p. injections of electrolyte solution at various doses (0, 4, 6, or 8 ml/day). Further groups were treated either with i.p. lavage, lavage with 1.5 mg/ml of gabexate, or i.p. injections of 100 mg/kg of gabexate without lavage. The potential benefits of the various regimens were assessed by measuring survival, various biochemical and histologic features, and alterations in hematocrit, pH, and blood gases. Increasing O2 concentrations reversed hypoxemia and acidosis, but had no effect on biochemical or morphologic alterations and did not improve survival. However, hydration by s.c. fluid markedly improved survival and normalized the hematocrit without having major effects on biochemical or morphologic alterations. Intraperitoneal fluid did not improve survival. Gabexate injections without lavage had a slight effect on survival and serum amylase concentration and very little effect on histology. Lavage without gabexate had a greater effect on survival, serum amylase, and histology. Addition of gabexate to the lavage fluid increased the beneficial effect of lavage. Increases in amylase and activated trypsin in ascites were markedly reduced by lavage and even more so by lavage with addition of gabexate. We conclude that sufficient hydration appears to be an important factor in supportive care for severe acute pancreatitis, whereas oxygenation without sufficient hydration has no major benefit. Peritoneal lavage with gabexate showed the greatest benefit of the various regimens for acute severe pancreatitis and is worthy of clinical trials.     

Prospective and randomized study of gabexate mesilate for the treatment of severe acute pancreatitis with organ dysfunction

BACKGROUND/AIMS: Exaggerated production of various proteases may account for the late presence of organ dysfunction in acute pancreatitis. This study examined the effects of early administration of gabexate mesilate on the condition of patients with severe acute pancreatitis and organ dysfunctions. METHODOLOGY: Fifty-two patients with acute pancreatitis and organ dysfunction were enrolled. The treatment group included 26 patients receiving intravenous gabexate mesilate infusion at a dose of 100 mg/hr for 7 days. APACHE-II score, clinical and biochemical parameters were monitored intensively. RESULTS: Coagulopathy ileus, and abdominal pain was significantly improved with gabexate mesilate. Gabexate mesilate reduced the necessity for surgical intervention and peritoneal lavage. The 7-day-mortality and 90-day-mortality rates were also significantly reduced with gabexate mesilate therapy. CONCLUSIONS: There are strong indications from this study that early intravenous gabexate mesilate infusion results in improved survival in acute pancreatitis with organ dysfunctions.     

Prevalence of normal serum amylase levels in patients with acute alcoholic pancreatitis

Acute alcoholic pancreatitis is uncommonly diagnosed when the serum amylase level is normal. We defined acute alcoholic pancreatitis as a clinical syndrome in which hyperamylasemia was not a necessary component and sought support for the diagnosis by ultrasonography and computed tomography of the pancreas. In 68 episodes of acute alcoholic pancreatitis identified in a one-year period, the serum amylase level was normal at the time of hospital admission in 32%. In 40 episodes, we performed ultrasonography and computed tomography within 48 hr of admission. The diagnosis was supported by ultrasonography in 43%, by computed tomography in 68%. Ultrasonography and computed tomography supported the diagnosis as frequently in patients with normal serum amylase levels as in patients with hyperamylasemia. We conclude that patients with acute alcoholic pancreatitis frequently have normal serum amylase levels. The widespread clinical practice of relying solely on hyperamylasemia to establish the diagnosis of acute alcoholic pancreatitis is unjustified and should be abandoned.     

Does gabexate mesilate affect serum concentrations of acute phase proteins after endoscopic retrograde cholangiopancreatography examination?

BACKGROUND/AIMS: To explore the possibility that the preventive effect of gabexate mesilate on endoscopic retrograde cholangiopancreatography-related acute pancreatitis may be mediated by its modulation of acute phase proteins. METHODOLOGY: Thirty consecutive patients who underwent endoscopic retrograde cholangiopancreatography were randomly assigned to receive 1g of gabexate mesilate (13 patients) or a placebo (17 patients) by continuous i.v. infusion starting 30 minutes before the endoscopy session and continuing for 12 hours afterward. In all patients, C-reactive protein, serum amyloid A and interleukin 6 serum concentrations were determined before endoscopy and 4, 8, 12 and 24 hours afterward. RESULTS: Interleukin 6 basal serum concentrations were not statistically different between patients who had been treated with gabexate mesilate and those who had received the placebo (P = 0.279), whereas C-reactive protein (P = 0.033) and serum amyloid A (P = 0.022) basal values were significantly lower in the gabexate mesilate group than in the placebo group. Compared to basal values, serum interleukin 6 concentrations significantly increased at 4 (P = 0.048) and at 8 (P = 0.025) hours; the increase of serum interleukin 6 concentrations was not significant at 12 (P = 0.092), but became significant at 24 (P = 0.025) hours. C-reactive protein and serum amyloid A serum concentrations increased significantly only at 12 (P = 0.001, P = 0.012, respectively) and 24 (P < 0.001, P = 0.013, respectively) hours. The modifications of serum concentrations of interleukin 6, C-reactive protein and serum amyloid A were not significantly different between the gabexate mesilate and the placebo groups. CONCLUSIONS: Gabexate mesilate does not affect serum concentrations of acute phase proteins after endoscopic retrograde cholangiopancreatography examination and it is able to prevent acute pancreatitis related to endoscopic retrograde cholangiopancreatography via a different mechanism than that explored in this study.