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Inhaled Anesthetics Exert Different Protective Properties in a Mouse Model of Ventilator-Induced Lung Injury

Strosing, Karl Michael MD, DESA; Faller, Simone PhD; Gyllenram, Veronica; Engelstaedter, Helen MD; Buerkle, Hartmut MD; Spassov, Sashko PhD; Hoetzel, Alexander MD, MA

doi: 10.1213/ANE.0000000000001296
Critical Care and Resuscitation: Research Report

BACKGROUND: Mechanical ventilation is an important perioperative tool in anesthesia and a lifesaving treatment for respiratory failure, but it can lead to ventilator-associated lung injury. Inhaled anesthetics have demonstrated protective properties in various models of organ damage. We compared the lung-protective potential of inhaled sevoflurane, isoflurane, and desflurane in a mouse model of ventilator-induced lung injury (VILI).

METHODS: C57BL/6N mice were randomized into 5 groups (n = 8/group). One group served as a control and 4 groups were subjected to mechanical ventilation with air (12 mL/kg tidal volume) for 6 hours. Ventilated animals were anesthetized with either ketamine and acepromazine, or 1 of 3 inhaled anesthetics: isoflurane, sevoflurane, or desflurane. Lung injury was assessed by lung histology, neutrophil counts, and interleukin-1β concentrations in bronchoalveolar lavage fluid. Antioxidant effects were explored by evaluation of production of reactive oxygen species (ROS) and glutathione content in lung tissue by immunofluorescence staining and confocal laser scanning microscopy. Changes in intercellular adhesion molecule-1 and src-protein-tyrosine-kinase levels were determined by real-time polymerase chain reaction and Western blot.

RESULTS: Compared with nonventilated controls, ventilated mice anesthetized with ketamine had thickened alveolar walls, elevated VILI scores, higher polymorph neutrophil counts, and increased ROS production. Mice anesthetized with isoflurane and sevoflurane showed thinner alveolar septa, lower VILI scores, lower polymorph neutrophil counts, and lower interleukin-1β concentrations than ketamine mice. The expression of intercellular adhesion molecule-1/src-protein-tyrosine-kinase was neither affected by mechanical ventilation nor affected by administration of inhaled anesthetics. Mice anesthetized with isoflurane and sevoflurane showed less ROS production and higher glutathione contents compared with ketamine mice. Unexpectedly, desflurane-ventilated mice showed similar signs of lung injury compared with mice ventilated with air alone and receiving ketamine anesthesia. Desflurane failed to inhibit inflammatory responses and ROS production in lung tissue and developed no antioxidant potential.

CONCLUSIONS: Although isoflurane and sevoflurane prevent ventilator-associated lung injury, desflurane does not. As an underlying mechanism, both inhaled anesthetics exert major anti-inflammatory and antioxidative effects.

Supplemental Digital Content is available in the text.Published ahead of print March 28, 2016

From the Department of Anaesthesiology and Critical Care Medicine, Freiburg University Medical Center, Freiburg, Germany.

Accepted for publication February 3, 2016.

Published ahead of print March 28, 2016

Funding: This work was supported by a grant from the Deutsche Forschungsgemeinschaft (Bonn, Germany) to Alexander Hoetzel (DFG HO 2464/3-1).

The authors declare no conflicts of interest.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website.

Reprints will not be available from the authors.

Address correspondence to Karl Michael Strosing, MD, DESA, Department of Anaesthesiology and Critical Care Medicine, Freiburg University Medical Center, Hugstetter Str. 55, D-79106, Freiburg, Germany. Address e-mail to

© 2016 International Anesthesia Research Society