Acute Pancreatitis
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《新英格兰医药杂志》
To the Editor: In his article on acute pancreatitis, Whitcomb (May 18 issue)1 does not mention the debate about the use of protease inhibitors, such as gabexate, as prophylaxis for pancreatitis induced by endoscopic retrograde cholangiopancreatography (ERCP), a potentially severe complication that occurs in up to 13.5 percent of patients undergoing the procedure. A recent meta-analysis by Seta et al.2 showed that the use of protease inhibitors significantly reduced the rate of death in moderate-to-severe pancreatitis. This finding indicates that gabexate should routinely be added to the usual standard of care, at least for patients who are more severely affected by this disease. Studies of pharmacologic prevention of pancreatitis after ERCP have had disappointing results,3 except for those involving gabexate, which has consistently shown a clinically appreciable effect in this setting.4,5,6 One important adverse aspect of gabexate has been the need to administer the drug by continuous infusion for about 12 hours, which renders this strategy not cost-effective. However, infusions lasting 6.5 hours have been shown to be as effective as longer infusions, with evident cost savings.6 It is unclear whether all patients undergoing ERCP would benefit from the use of gabexate or only those who are at greater risk for pancreatitis — for example, those for whom sphincterotomy is planned.
Giuseppe Famularo, M.D.
Giovanni Minisola, M.D.
San Camillo Hospital
00152 Rome, Italy
gfamularo@scamilloforlanini.rm.it
Claudio De Simone, M.D.
University of L'Aquila
67100 L'Aquila, Italy
References
Whitcomb DC. Acute pancreatitis. N Engl J Med 2006;354:2142-2150.
Seta T, Noguchi Y, Shimada T, Shikata S, Fukui T. Treatment of acute pancreatitis with protease inhibitors: a meta-analysis. Eur J Gastroenterol Hepatol 2004;16:1287-1293.
Pande H, Thuluvath P. Pharmacological prevention of post-endoscopic retrograde cholangiopancreatography pancreatitis. Drugs 2003;63:1799-1812.
Cavallini G, Tittobello A, Frulloni L, et al. Gabexate for the prevention of pancreatic damage related to endoscopic retrograde cholangiopancreatography. N Engl J Med 1996;335:919-923.
Mariani A. Pharmacological prevention of post-ERCP pancreatitis: which therapy is best? JOP 2003;4:68-74.
Masci E, Cavallini G, Mariani A, et al. Comparison of two dosing regimens of gabexate in the prophylaxis of post-ERCP pancreatitis. Am J Gastroenterol 2003;98:2182-2186.
The author replies: Famularo et al. highlight the potential benefits of gabexate, a protease inhibitor that is not available in the United States and that has not been shown to be of significant value in several studies.1,2 The meta-analysis by Seta et al. showed that the risk of death was reduced by 7 percent in a subgroup of patients with moderate-to-severe disease, but 40 percent of these studies used the protease inhibitor aprotinin, rather than gabexate, and were conducted before 1980, when the treatment of severe cases of acute pancreatitis differed from that used today.
Is it cost-effective to infuse gabexate for 6.5 hours after ERCP? The answer depends on many factors, including the incidence of pancreatitis after ERCP with and without intervention. The recent use of pancreatic stents in high-risk patients,3 for example, has reduced the incidence of pancreatitis after ERCP to less than 5 percent (rather than 13.5 percent, as cited by Famularo et al.), with less than 1 percent of cases categorized as severe.4 Thus, with improved techniques, the use of prolonged infusions for pharmacologic prophylaxis against severe pancreatitis after ERCP may no longer be justified.
David C. Whitcomb, M.D., Ph.D.
University of Pittsburgh
Pittsburgh, PA 15213
whitcomb@pitt.edu
References
Heinrich S, Schafer M, Rousson V, Clavien PA. Evidence-based treatment of acute pancreatitis: a look at established paradigms. Ann Surg 2006;243:154-168.
Andriulli A, Caruso N, Quitadamo M, et al. Antisecretory vs. antiproteasic drugs in the prevention of post-ERCP pancreatitis: the evidence-based medicine derived from a meta-analysis study. JOP 2003;4:41-48.
Tarnasky PR, Palesch YY, Cunningham JT, Mauldin PD, Cotton PB, Hawes RH. Pancreatic stenting prevents pancreatitis after biliary sphincterotomy in patients with sphincter of Oddi dysfunction. Gastroenterology 1998;115:1518-1524.
Suissa A, Yassin K, Lavy A, et al. Outcome and early complications of ERCP: a prospective single center study. Hepatogastroenterology 2005;52:352-355.
Giuseppe Famularo, M.D.
Giovanni Minisola, M.D.
San Camillo Hospital
00152 Rome, Italy
gfamularo@scamilloforlanini.rm.it
Claudio De Simone, M.D.
University of L'Aquila
67100 L'Aquila, Italy
References
Whitcomb DC. Acute pancreatitis. N Engl J Med 2006;354:2142-2150.
Seta T, Noguchi Y, Shimada T, Shikata S, Fukui T. Treatment of acute pancreatitis with protease inhibitors: a meta-analysis. Eur J Gastroenterol Hepatol 2004;16:1287-1293.
Pande H, Thuluvath P. Pharmacological prevention of post-endoscopic retrograde cholangiopancreatography pancreatitis. Drugs 2003;63:1799-1812.
Cavallini G, Tittobello A, Frulloni L, et al. Gabexate for the prevention of pancreatic damage related to endoscopic retrograde cholangiopancreatography. N Engl J Med 1996;335:919-923.
Mariani A. Pharmacological prevention of post-ERCP pancreatitis: which therapy is best? JOP 2003;4:68-74.
Masci E, Cavallini G, Mariani A, et al. Comparison of two dosing regimens of gabexate in the prophylaxis of post-ERCP pancreatitis. Am J Gastroenterol 2003;98:2182-2186.
The author replies: Famularo et al. highlight the potential benefits of gabexate, a protease inhibitor that is not available in the United States and that has not been shown to be of significant value in several studies.1,2 The meta-analysis by Seta et al. showed that the risk of death was reduced by 7 percent in a subgroup of patients with moderate-to-severe disease, but 40 percent of these studies used the protease inhibitor aprotinin, rather than gabexate, and were conducted before 1980, when the treatment of severe cases of acute pancreatitis differed from that used today.
Is it cost-effective to infuse gabexate for 6.5 hours after ERCP? The answer depends on many factors, including the incidence of pancreatitis after ERCP with and without intervention. The recent use of pancreatic stents in high-risk patients,3 for example, has reduced the incidence of pancreatitis after ERCP to less than 5 percent (rather than 13.5 percent, as cited by Famularo et al.), with less than 1 percent of cases categorized as severe.4 Thus, with improved techniques, the use of prolonged infusions for pharmacologic prophylaxis against severe pancreatitis after ERCP may no longer be justified.
David C. Whitcomb, M.D., Ph.D.
University of Pittsburgh
Pittsburgh, PA 15213
whitcomb@pitt.edu
References
Heinrich S, Schafer M, Rousson V, Clavien PA. Evidence-based treatment of acute pancreatitis: a look at established paradigms. Ann Surg 2006;243:154-168.
Andriulli A, Caruso N, Quitadamo M, et al. Antisecretory vs. antiproteasic drugs in the prevention of post-ERCP pancreatitis: the evidence-based medicine derived from a meta-analysis study. JOP 2003;4:41-48.
Tarnasky PR, Palesch YY, Cunningham JT, Mauldin PD, Cotton PB, Hawes RH. Pancreatic stenting prevents pancreatitis after biliary sphincterotomy in patients with sphincter of Oddi dysfunction. Gastroenterology 1998;115:1518-1524.
Suissa A, Yassin K, Lavy A, et al. Outcome and early complications of ERCP: a prospective single center study. Hepatogastroenterology 2005;52:352-355.