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 StudyReportar como inadecuado




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Journal of Intensive Care

, 2:67

First Online: 31 December 2014Received: 10 July 2014Accepted: 08 December 2014

Abstract

BackgroundNeutrophil 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.

MethodsA 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.

ResultsPatients 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.

ConclusionsAlthough 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.

KeywordsAcute lung injury Extravascular lung water Pulmonary edema Pulmonary vascular permeability index Transpulmonary thermodilution technique AbbreviationsAPACHEAcute physiology and chronic health evaluation

ARDSAcute respiratory distress syndrome

CVPCentral venous pressure

EVLWExtravascular lung water

EVLWiExtravascular lung water index

NENeutrophil elastase

PEEPPositive end-expiratory pressure

PVPIPulmonary vascular permeability index

SOFASequential organ failure assessment

CIConfidence interval

Electronic supplementary materialThe online version of this article doi:10.1186-s40560-014-0067-y contains supplementary material, which is available to authorized users.

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