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Continuous Regional Arterial Infusion of Protease Inhibitors Has No Efficacy in the Treatment of Severe Acute Pancreatitis: A Retrospective Multicenter Cohort Study

Horibe, Masayasu MD; Sasaki, Mitsuhito MD; Sanui, Masamitsu MD, PhD; Sugiyama, Daisuke MD, PhD; Iwasaki, Eisuke MD, PhD; Yamagishi, Yoshiyuki MD, PhD; Sawano, Hirotaka MD, PhD; Goto, Takashi MD; Ikeura, Tsukasa MD, PhD; Hamada, Tsuyoshi MD, PhD; Oda, Takuya MD; Yasuda, Hideto MD; Shinomiya, Wataru MD; Miyazaki, Dai MD; Hirose, Kaoru MD; Kitamura, Katsuya MD, PhD; Chiba, Nobutaka MD, PhD; Ozaki, Tetsu MD; Yamashita, Takahiro MD; Koinuma, Toshitaka MD; Oshima, Taku MD, PhD; Yamamoto, Tomonori MD; Hirota, Morihisa MD, PhD; Moriya, Takashi MD, PhD; Shirai, Kunihiro MD, PhD; Mayumi, Toshihiko MD, PhD; Kanai, Takanori MD, PhD

doi: 10.1097/MPA.0000000000000775
Original Articles

Objective The aim of this study is to assess the effectiveness of continuous regional arterial infusion (CRAI) of protease inhibitors in patients with severe acute pancreatitis (SAP) including acute necrotizing pancreatitis.

Methods This retrospective study was conducted among 44 institutions in Japan from 2009 to 2013. Patients 18 years or older diagnosed with SAP according to the criteria of the Japanese Ministry of Health, Labour and Welfare study group (2008) were consecutively enrolled. We evaluated the association between CRAI of protease inhibitors and mortality, incidence of infection, and the need for surgical intervention using multivariable logistic regression analysis.

Results Of 1159 patients admitted, 1097 patients with all required data were included for analysis. Three hundred and seventy-four (34.1%) patients underwent CRAI of protease inhibitors and 723 (65.9%) did not. In multivariable analysis, CRAI of protease inhibitors was not associated with a reduction in mortality, infection rate, or need for surgical intervention (odds ratio [OR] 0.79, 95% confidence interval [CI] 0.47–1.32, P = 0.36; OR 0.97, 95% CI 0.61–1.54, P = 0.89; OR 0.76, 95% CI 0.50–1.15, P = 0.19; respectively).

Conclusions Continuous regional arterial infusion of protease inhibitors was not efficacious in the treatment of patients with SAP.

From the *Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine; †Department of Gastroenterology and Hepatology, Tokyo Metropolitan Tama Medical Center; ‡Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Tokyo; §Department of Anesthesiology and Critical Care Medicine, Jichi Medical University Saitama Medical Center, Saitama; ∥Department of Preventive Medicine and Public Health, School of Medicine, Keio University, Tokyo; ¶Senri Critical Care Medical Center, Osaka Saiseikai Senri Hospital, Osaka; #Department of Anesthesiology and Intensive Care, Hiroshima City Hiroshima Citizens Hospital, Hiroshima; **The Third Department of Internal Medicine, Kansai Medical University, Osaka; ††Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo; ‡‡Department of General Internal Medicine, Iizuka Hospital, Fukuoka; §§Department of Emergency and Critical Care Medicine, Japanese Red Cross Musashino Hospital, Tokyo; ∥∥Advanced Emergency Medical and Critical Care Center, Japanese Red Cross Maebashi Hospital, Gunma; ¶¶Department of Emergency Medicine, Shonan Kamakura General Hospital, Kanagawa; ##Division of Gastroenterology, Department of Medicine, Showa University School of Medicine; ***Department of Emergency and Critical Care Medicine, Nihon University Hospital, Tokyo; †††Department of Acute Care and General Medicine, Saiseikai Kumamoto Hospital, Kumamoto;‡‡‡Emergency Medical Center, Fukuyama City Hospital, Hiroshima; §§§Division of Intensive Care, Department of Anesthesiology and Intensive Care Medicine, Jichi Medical University School of Medicine, Tochigi; ∥∥∥Department of Traumatology and Critical Care Medicine, Chiba University Graduate School of Medicine, Chiba; ¶¶¶Department of Critical Care Medicine, Osaka City University, Osaka; ###Division of Gastroenterology, Tohoku University Hospital, Miyagi; ****Division of Emergency and Critical Care Medicine, Department of Acute Medicine, Nihon University School of Medicine, Tokyo; ††††Department of Emergency and Disaster Medicine, Gifu University Graduate School of Medicine, Gifu; and ‡‡‡‡Department of Emergency Medicine, School of Medicine University of Occupational and Environmental Health, Fukuoka, Japan.

Received for publication October 7, 2015; accepted October 7, 2016.

Address correspondence to: Masamitsu Sanui, MD, PhD, Department of Anesthesiology and Critical Care Medicine, Jichi Medical University Saitama Medical Center, 1-847 Amanumachou, Omiya-ku, Saitama, 330-8503, Japan (e-mail:

The authors declare no conflict of interest.

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