A single, 30 minutes pretreatment with Isoflurane or Sevoflurane is not protective against high tidal volume induced lung injury in rats

Abstract

Background: Volatile anesthetics (VA) may exert organ-protective effects in various experimental and clinical settings. Mechanical ventilation (MV) induces an inflammatory response and, depending on the ventilator settings chosen, injury in the lungs. It is unclear if prophylactic inhaled VA applied on healthy lungs prior to MV are protective regarding these effects. Methods: Healthy, spontaneously breathing rats were exposed for 30 minutes to either isoflurane (1.8 Vol %), sevoflurane (3.0 Vol %) or no VA. Animals were allowed to recover, intraperitoneally anesthetized and then mechanically ventilated for 4 hours with either high (21 ml/kg body weight) or low (9 ml/kg body weight) tidal volume (n = 12 per group). Cardiorespiratory parameters and systemic inflammation were assessed at the beginning and during mechanical ventilation. Cellular, non-cellular and histologic markers of pulmonary injury and inflammation were determined. Results: Irrespective of VA pretreatment, MV with high VT negatively affected markers of lung integrity such as arterial oxygenation and lung wetto-dry ratio. Following VA pretreatment we found no protective effects on lung function but there were changes in some markers of inflammation such as a decrease in blood lymphocyte counts and an increase in interleukin 6 concentration in plasma and lung lavage fluid. These effects were heterogeneous regarding group allocation and time points. Conclusions: In this in in vivo animal model, prophylactic administration of inhaled VA was not beneficial or protective regarding ventilation induced lung injury. However, there were effects suggestive of a modulation of inflammatory markers associated with VA prophylaxis. The clinical or biological relevance of these findings so far remain unclear and should be subject to further studies. BackgroundAcute lung injury and its most severe form, acute respiratory distress syndrome are devastating clinical conditions, with high mortality rates (1). Mechanical ventilation (MV) is a mainstay of treatment of such patients, but may exert detrimental effects on the lung and worsen the situation (2). In addition, mechanical ventilation of healthy lungs, depending on the tidal volume applied, can cause the clinical findings of ALI (3). The deleterious pulmonary effects of MV are summarized under the term ventilator-induced lung injury (VILI).