• Matthieu Jabaudon, Pierre Boucher, Etienne Imhoff, Russell Chabanne, Jean-Sébastien Faure, Laurence Roszyk, Sandrine Thibault, Raiko Blondonnet, Gael Clairefond, Renaud Guérin, Sébastien Perbet, Sophie Cayot, Thomas Godet, Bruno Pereira, Vincent Sapin, Jean-Etienne Bazin, Emmanuel Futier, and Jean-Michel Constantin.
• CHU Clermont-Ferrand, Department of Perioperative Medicine, Clermont-Ferrand, France.
• Am. J. Respir. Crit. Care Med. 2016 Sep 9.

RationaleSevoflurane improves gas exchange, reduces alveolar edema and inflammation in preclinical studies of lung injury but its therapeutic effects have never been investigated in acute respiratory distress syndrome (ARDS).ObjectivesTo assess whether sevoflurane would improve gas exchange and inflammation in ARDS.MethodsWe did a parallel, open-label single center randomized controlled trial at 3 intensive care units from a french university hospital between April, 2014, and February, 2016. Adult patients were randomized within 24 hours of moderate-to-severe ARDS onset to receive either intravenous midazolam or inhaled sevoflurane for 48 hours. The primary outcome was the partial pressure of arterial oxygen to fractional inspired oxygen concentration (PaO2/FiO2) ratio on day 2. Secondary endpoints included alveolar and plasma levels of cytokines and soluble form of the receptor for advanced glycation end-products (sRAGE), and safety. Investigators who did the analyses were masked to group allocation. Analysis was by intention-to-treat.Measurements And Main Results25 patients were assigned to the sevoflurane group and 25 to the midazolam group. On day 2, PaO2/FiO2 ratio was higher in the sevoflurane group than in the midazolam group (mean ± standard deviation, 205 ± 56 versus 166±59, respectively, P=0.04). There was a significant reduction over time in cytokines and sRAGE levels in the sevoflurane group, compared to the midazolam group, and no serious adverse event was observed with sevoflurane.ConclusionsIn ARDS patients, use of inhaled sevoflurane improved oxygenation and decreased levels of a marker of epithelial injury and of some inflammatory markers, compared to midazolam. Clinical trial registration available at www.clinicaltrials.gov, ID NCT02166853.

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