Effect of a selective neutrophil elastase inhibitor on mortality and ventilator-free days in patients with increased extravascular lung water: A post hoc analysis of the PiCCO Pulmonary Edema Study

Takashi Tagami, Ryoichi Tosa, Mariko Omura, Hidetada Fukushima, Tadashi Kaneko, Tomoyuki Endo, Hiroshi Rinka, Akira Murai, Junko Yamaguchi, Kazuhide Yoshikawa, Nobuyuki Saito, Hideaki Uzu, Yoichi Kase, Makoto Takatori, Hiroo Izumino, Toshiaki Nakamura, Ryutarou Seo, Yasuhide Kitazawa, Manabu Sugita, Hiroyuki TakahashiYuichi Kuroki, Takayuki Irahara, Takashi Kanemura, Hiroyuki Yokota, Shigeki Kushimoto

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22 Citations (Scopus)

Abstract

Background: Neutrophil elastase plays an important role in the development and progression of acute respiratory distress syndrome (ARDS). Although the selective elastase inhibitor, sivelestat, is widely used in Japan for treating ARDS patients, its effectiveness remains controversial. The aim of the current study was to investigate the effects of sivelestat in ARDS patients with evidence of increased extravascular lung water by re-analyzing a large multicenter study database. Methods: A post hoc analysis of the PiCCO Pulmonary Edema Study was conducted. This multicenter prospective cohort study included 23 institutions in Japan. Adult mechanically ventilated ARDS patients with an extravascular lung water index of >10 mL/kg were included and propensity score analyses were performed. The endpoints were 28-day mortality and ventilator-free days (VFDs).Results: Patients were categorized into sivelestat (n = 87) and control (n = 77) groups, from which 329 inverse probability-weighted group patients (162 vs. 167) were generated. The overall 28-day mortality was 31.1% (51/164). There was no significant difference in 28-day mortality between the study groups (sivelestat vs. control; unmatched: 29.9% vs. 32.5%; difference, -2.6%, 95% confidence interval (CI), -16.8 to 14.2; inverse probability-weighted: 24.7% vs. 29.5%, difference, -4.8%, 95% CI, -14.4 to 9.6). Although administration of sivelestat did not alter the number of ventilator-free days (VFDs) in the unmatched (9.6 vs. 9.7 days; difference, 0.1, 95% CI, -3.0 to 3.1), the inverse probability-weighted analysis identified significantly more VFDs in the sivelestat group than in the control group (10.7 vs. 8.4 days, difference, -2.3, 95% CI, -4.4 to -0.2).Conclusions: Although sivelestat did not significantly affect 28-day mortality, this treatment may have the potential to increase VFDs in ARDS patients with increased extravascular lung water. Prospective randomized controlled studies are required to confirm the results of the current study.

Original languageEnglish
Article number67
JournalJournal of Intensive Care
Volume2
Issue number1
DOIs
Publication statusPublished - 2014 Dec 31

Keywords

  • Acute lung injury
  • Extravascular lung water
  • Pulmonary edema
  • Pulmonary vascular permeability index
  • Transpulmonary thermodilution technique

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine

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    Tagami, T., Tosa, R., Omura, M., Fukushima, H., Kaneko, T., Endo, T., Rinka, H., Murai, A., Yamaguchi, J., Yoshikawa, K., Saito, N., Uzu, H., Kase, Y., Takatori, M., Izumino, H., Nakamura, T., Seo, R., Kitazawa, Y., Sugita, M., ... Kushimoto, S. (2014). Effect of a selective neutrophil elastase inhibitor on mortality and ventilator-free days in patients with increased extravascular lung water: A post hoc analysis of the PiCCO Pulmonary Edema Study. Journal of Intensive Care, 2(1), [67]. https://doi.org/10.1186/s40560-014-0067-y