TY - JOUR
T1 - Effect of a selective neutrophil elastase inhibitor on mortality and ventilator-free days in patients with increased extravascular lung water
T2 - A post hoc analysis of the PiCCO Pulmonary Edema Study
AU - Tagami, Takashi
AU - Tosa, Ryoichi
AU - Omura, Mariko
AU - Fukushima, Hidetada
AU - Kaneko, Tadashi
AU - Endo, Tomoyuki
AU - Rinka, Hiroshi
AU - Murai, Akira
AU - Yamaguchi, Junko
AU - Yoshikawa, Kazuhide
AU - Saito, Nobuyuki
AU - Uzu, Hideaki
AU - Kase, Yoichi
AU - Takatori, Makoto
AU - Izumino, Hiroo
AU - Nakamura, Toshiaki
AU - Seo, Ryutarou
AU - Kitazawa, Yasuhide
AU - Sugita, Manabu
AU - Takahashi, Hiroyuki
AU - Kuroki, Yuichi
AU - Irahara, Takayuki
AU - Kanemura, Takashi
AU - Yokota, Hiroyuki
AU - Kushimoto, Shigeki
N1 - Publisher Copyright:
© 2014 Tagami et al.; licensee BioMed Central Ltd.
PY - 2014/12/31
Y1 - 2014/12/31
N2 - 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.
AB - 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.
KW - Acute lung injury
KW - Extravascular lung water
KW - Pulmonary edema
KW - Pulmonary vascular permeability index
KW - Transpulmonary thermodilution technique
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U2 - 10.1186/s40560-014-0067-y
DO - 10.1186/s40560-014-0067-y
M3 - Article
AN - SCOPUS:84979195063
VL - 2
JO - Journal of Intensive Care
JF - Journal of Intensive Care
SN - 2052-0492
IS - 1
M1 - 67
ER -