Preventive Effects of Ulinastatin on Post-Endoscopic Retrograde Cholangiopancreatography Pancreatitis in High-Risk Patients: A Prospective, Randomized, Placebo-Controlled Trial

Objectives: Previous studies have shown that ulinastatin may be effective at preventing pancreatitis after endoscopic retrograde cholangiopancreatography (ERCP). However, routine administration of ulinastatin is unlikely to be cost-effective. So the aim of this prospective study was to evaluate the effectiveness of low-dose ulinastatin at preventing pancreatitis in patients at high risk of post-ERCP pancreatitis. Methods: A total of 227 patients (mean age, 63 years; 54% men) were randomized to receive placebo (n = 108) or active drug (n = 119) immediately after ERCP and received active drug (100,000 U of ulinastatin) or placebo. Occurrence of post-ERCP pancreatitis and hyperamylasemia were compared between the 2 groups. Results: The overall incidence of pancreatitis was 6.2%, and no significant differences were observed between placebo- and ulinastatin-treated patients in terms of the frequencies of pancreatitis (5.6% vs 6.7%), abdominal pain, or hyperamylasemia. Pancreatic duct acinarization, papillectomy of ampulla of Vater adenoma, difficult cannulation, and female sex were identified as risk factors for pancreatitis in univariate analysis. Conclusions: Low-dose prophylactic treatment with ulinastatin immediately after ERCP did not show a beneficial influence on the incidence of post-ERCP pancreatitis and hyperamylasemia in high-risk patients.

[1]  N. Ishimura,et al.  Ulinastatin shows preventive effect on post‐endoscopic retrograde cholangiopancreatography pancreatitis in a multicenter prospective randomized study , 2006, Journal of gastroenterology and hepatology.

[2]  Y. Shiratori,et al.  Ulinastatin for pancreatitis after endoscopic retrograde cholangiopancreatography: a randomized, controlled trial. , 2005, Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association.

[3]  A. Andriulli,et al.  Prophylaxis of ERCP-related pancreatitis: a randomized, controlled trial of somatostatin and gabexate mesylate. , 2004, Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association.

[4]  M. Freeman,et al.  Prevention of post-ERCP pancreatitis: a comprehensive review. , 2004, Gastrointestinal endoscopy.

[5]  A. Andriulli,et al.  Gabexate or somatostatin administration before ERCP in patients at high risk for post-ERCP pancreatitis: a multicenter, placebo-controlled, randomized clinical trial. , 2002, Gastrointestinal endoscopy.

[6]  F. Prat,et al.  Nifedipine for prevention of post-ERCP pancreatitis: a prospective, double-blind randomized study. , 2002, Gastrointestinal endoscopy.

[7]  S. Raptis,et al.  Octreotide versus hydrocortisone versus placebo in the prevention of post-ERCP pancreatitis: a multicenter randomized controlled trial. , 2002, Gastrointestinal Endoscopy.

[8]  A. Budzyńska,et al.  A Prospective, Randomized, Placebo-Controlled Trial of Prednisone and Allopurinol in the Prevention of ERCP-Induced Pancreatitis , 2001, Endoscopy.

[9]  O. Moine,et al.  Interleukin 10 reduces the incidence of pancreatitis after therapeutic endoscopic retrograde cholangiopancreatography. , 2001, Gastroenterology.

[10]  S. Fan,et al.  Prophylactic effect of somatostatin on post-ERCP pancreatitis: a randomized controlled trial. , 1999, Gastrointestinal endoscopy.

[11]  P. Fina,et al.  Major early complications from diagnostic and therapeutic ERCP: a prospective multicenter study. , 1998, Gastrointestinal endoscopy.

[12]  T. Zágoni,et al.  Complications of endoscopic biliary sphincterotomy. , 1997, The New England journal of medicine.

[13]  A. Fürstenberg,et al.  Post-ERP pancreatitis as a model for cytokine induced acute phase response in acute pancreatitis. , 1997, Gut.

[14]  A. Mariani,et al.  Gabexate for the prevention of pancreatic damage related to endoscopic retrograde cholangiopancreatography. Gabexate in digestive endoscopy--Italian Group. , 1996, The New England journal of medicine.

[15]  T. Hirano,et al.  Effect of urinary trypsin inhibitor on pancreatic cellular and lysosomal fragility in cerulein-induced acute pancreatitis in rats , 1993, Digestive Diseases and Sciences.

[16]  K. Ohlsson,et al.  Distribution and elimination of intravenously injected urinary trypsin inhibitor. , 1991, Scandinavian journal of clinical and laboratory investigation.

[17]  C Liguory,et al.  Endoscopic sphincterotomy complications and their management: an attempt at consensus. , 1991, Gastrointestinal endoscopy.

[18]  M. Otsuki,et al.  The Protective Effect of the Trypsin Inhibitor Urinastatin on Cerulein‐Induced Acute Pancreatitis in Rats , 1988, Pancreas.

[19]  H. Ohnishi,et al.  Effects of urinary trypsin inhibitor on pancreatic enzymes and experimental acute pancreatitis , 2005, Digestive Diseases and Sciences.

[20]  S. Fan,et al.  Title Intravenous bolus somatostatin after diagnostic cholangiopancreatography reduces the incidence of pancreatitis associated with therapeutic endoscopic retrograde cholangiopancreatography procedures : A randomised controlled trial , 2003 .

[21]  A. Mariani.  Pharmacological prevention of post-ERCP pancreatitis: which therapy is best? , 2003, JOP : Journal of the pancreas.

[22]  L. Frulloni,et al.  Antiproteasic agents in the prevention of post-ERCP pancreatitis: rationale for use and clinical results. , 2003, JOP : Journal of the pancreas.