Pancreas. 2017 Apr;46(4):510-517.

Continuous regional arterial infusion of protease inhibitors has no efficacy in the treatment of severe acute pancreatitis: A retrospective multicenter cohort study.

Horibe M, Sasaki M, Sanui M, Sugiyama D, Iwasaki E, Yamagishi Y, Sawano H, Goto T, Ikeura T, Hamada T, Oda T, Yasuda H, Shinomiya W, Miyazaki D, Hirose K, Kitamura K, Chiba N, Ozaki T, Yamashita T, Koinuma T, Oshima T, Yamamoto T, Hirota M, Moriya T, Shirai K, Mayumi T, Kanai T

PMID: 27977624



Continuous regional arterial infusion (CRAI) of protease inhibitors is a promising method of potentially reducing mortality and preventing the development of pancreatic infection in patients with acute necrotizing pancreatitis (ANP).1 Laboratory data show that protease inhibitors exert broad inhibitory actions on pancreatic enzymes, systemic coagulation, and production of cytokines and it may potentially improve various derangements of microcirculation in patients with ANP.2 CRAI of a protease inhibitor through a catheter placed into an artery supplying the inflamed pancreas can dramatically increase delivery, with a five times greater concentration in the pancreatic parenchyma compared to intravenous infusions. 3


To our knowledge, this is the first large retrospective multi-center study to examine the efficacy of CRAI, performed at 44 institutions in Japan. We collected data from 1159 patients with severe acute pancreatitis diagnosed based on the criteria of the Japanese Ministry of Health, Labour and Welfare study group for acute pancreatitis severity (2008). Of 1159 patients, complete data sets for 1097 patients were used in the primary multivariable analysis.


The results of the primary analysis show that CRAI of protease inhibitors has no efficacy in reducing mortality, infection rates, or the need for surgical intervention in patients with severe acute pancreatitis. However, a preplanned subgroup analysis revealed that the requirement for surgical intervention was significantly lower in the CRAI group than in the non-CRAI group among 101 patients with greater than 50% necrosis of the whole pancreas (Fig 1).


This study has several limitations, most of which are associated with the retrospective nature of the study. To further examine whether CRAI of protease inhibitors has beneficial effects on patients with severe ANP, a well-powered prospective study is required. Therefore, we launched the SANADA (multicenter proSpective cohort in pAtieNts with severe And milD Acute pancreatitis) study in January 2017 (University Hospital Medical Information Network ID 000025468). This study will provide answers for important clinical questions regarding acute pancreatitis along with the effectiveness of the CRAI in patients with severe ANP.



1. Takeda K, Matsuno S, Sunamura M, Kakugawa Y. Continuous regional arterial infusion of protease inhibitor and antibiotics in acute necrotizing pancreatitis. Am J Surg 1996;171:394-8.
2. Gabryelewicz A, Prokopowicz J, Bodzenta A, Bielecki W, Rydzewska G. Effect of FUT-175 (nafamstat mesilate) on platelets in canine acute experimental pancreatitis. Digestion 1988;40:19-24.
3. Kakugawa Y, Takeda K, Sunamura M, Kawaguchi S, Kobari M, Matsuno S. [Effect of continuous arterial infusion of protease inhibitor on experimental acute pancreatitis induced by closed duodenal loop obstruction]. Nihon Shokakibyo Gakkai Zasshi 1990;87:1444-50.