Volatile anesthetics improve survival after cecal ligation and puncture

Sepsis and septic shock remain the leading causes of death in intensive care units worldwide.1 Complex pathophysiology together with heterogeneous disease patterns are key features making the treatment of sepsis extremely challenging.2–5 Numerous approaches have been undertaken to attenuate the harmful host response to infection, with a mostly unsuccessful translation into clinical outcome. Despite new pathophysiological insights and major efforts in developing goal-directed therapies, mortality in septic patients remains considerably high, and the treatment of late stage diagnosed patients is generally associated with bad outcome.6 Volatile anesthetics such as desflurane, isoflurane, and sevoflurane have been identified as effective modifiers of the inflammatory response in various states of tissue injury, exerting beneficial effects on organ function and overall outcome in both animals7–12 and patients.13–16 Potential benefits of the application of volatile anesthetics in in vivo models of experimental sepsis have not been systematically explored, and their effect on survival remains unclear. Previous studies elucidating the protective potential of volatile anesthetics have traditionally focused on ischemia–reperfusion injury and not on sepsis. In addition, biomarkers of organ injury were determined, but outcome parameters were not.17 In this study, we investigated in a model of severe murine sepsis with intraabdominal focus (peritonitis) whether the volatile anesthetics desflurane, isoflurane, and sevoflurane impact on overall survival of septic animals. The cecal ligation and puncture (CLP) model is considered the “gold standard” in sepsis research with a disease profile similar to that in human sepsis in that it encompasses more of the clinical features and drug responses of human sepsis, than, for example, the lipopolysaccharide model,18,19 despite the absence of some key features (e.g., kidney and lung injury). In this study, mice were exposed to desflurane, isoflurane, or sevoflurane during induction of sepsis (conditioning). To investigate the effect in a postconditioning setting, desflurane and sevoflurane were applied 24 h after the CLP procedure, when the mice showed pronounced symptoms of inflammation. Survival as well as markers of renal and hepatic organ function was compared with the CLP group without intervention. Being aware of the limitations of animal models of sepsis, the current study illustrates the beneficial effects of the volatile anesthetics desflurane and sevoflurane in states of severe inflammation leading to a remarkably improved 7-day survival and reduced end-organ damage.