Sevoflurane for Sedation in Acute Respiratory Distress Syndrome. A Randomized Controlled Pilot Study.
Sevoflurane improves gas exchange, and 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).



To assess whether sevoflurane would improve gas exchange and inflammation in ARDS.



We did a parallel, open-label single-center randomized controlled trial at three 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 PaO2/FiO2ratio on Day 2. Secondary endpoints included alveolar and plasma levels of cytokines and soluble form of the receptor for advanced glycation end-products, and safety. Investigators who did the analyses were masked to group allocation. Analysis was by intention to treat.



Twenty-five patients were assigned to the sevoflurane group and 25 to the midazolam group. On Day 2, PaO2/FiO2ratio was higher in the sevoflurane group than in the midazolam group (mean ± SD, 205 ± 56 vs. 166 ± 59, respectively; P = 0.04). There was a significant reduction over time in cytokines and soluble form of the receptor for advanced glycation end-products levels in the sevoflurane group, compared with the midazolam group, and no serious adverse event was observed with sevoflurane.



In patients with ARDS, use of inhaled sevoflurane improved oxygenation and decreased levels of a marker of epithelial injury and of some inflammatory markers, compared with midazolam. Clinical trial registered with www.clinicaltrials.gov (NCT 02166853).
1 Department of Perioperative Medicine.|2 Clermont Université, Université d'Auvergne, Clermont-Ferrand, France.
Matthieu
0000-0002-8121-1680
M
Jabaudon
1 Department of Perioperative Medicine.
Pierre
P
Boucher
1 Department of Perioperative Medicine.
Etienne
E
Imhoff
1 Department of Perioperative Medicine.
Russell
R
Chabanne
1 Department of Perioperative Medicine.
Jean-Sébastien
JS
Faure
3 Department of Medical Biochemistry and Molecular Biology, and.|2 Clermont Université, Université d'Auvergne, Clermont-Ferrand, France.
Laurence
L
Roszyk
4 Department of Clinical Research and Innovation (DRCI), CHU Clermont-Ferrand, Clermont-Ferrand, France; and.
Sandrine
S
Thibault
1 Department of Perioperative Medicine.|2 Clermont Université, Université d'Auvergne, Clermont-Ferrand, France.
Raiko
R
Blondonnet
2 Clermont Université, Université d'Auvergne, Clermont-Ferrand, France.
Gael
G
Clairefond
1 Department of Perioperative Medicine.
Renaud
R
Guérin
1 Department of Perioperative Medicine.|2 Clermont Université, Université d'Auvergne, Clermont-Ferrand, France.
Sébastien
S
Perbet
1 Department of Perioperative Medicine.
Sophie
S
Cayot
1 Department of Perioperative Medicine.
Thomas
T
Godet
4 Department of Clinical Research and Innovation (DRCI), CHU Clermont-Ferrand, Clermont-Ferrand, France; and.
Bruno
B
Pereira
3 Department of Medical Biochemistry and Molecular Biology, and.|2 Clermont Université, Université d'Auvergne, Clermont-Ferrand, France.
Vincent
V
Sapin
1 Department of Perioperative Medicine.
Jean-Etienne
JE
Bazin
1 Department of Perioperative Medicine.|2 Clermont Université, Université d'Auvergne, Clermont-Ferrand, France.
Emmanuel
E
Futier
1 Department of Perioperative Medicine.|2 Clermont Université, Université d'Auvergne, Clermont-Ferrand, France.
Jean-Michel
JM
Constantin
D000368:Aged; D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D018686:Anesthetics, Intravenous / Q000008:administration & dosage; D005260:Female; D005602:France; D006801:Humans; D008297:Male; D008738:Methyl Ethers / Q000494:pharmacology*; D008874:Midazolam / Q000008:administration & dosage; D008875:Middle Aged; D010865:Pilot Projects; D012128:Respiratory Distress Syndrome / Q000188:drug therapy*; D000077149:Sevoflurane; D016896:Treatment Outcome
D018685:Anesthetics, Inhalation; D018686:Anesthetics, Intravenous; D008738:Methyl Ethers; D000077149:Sevoflurane; D008874:Midazolam
acute respiratory distress syndrome; cytokines; gas exchange; receptor for advanced glycation end-products; sevoflurane