Impact of a long-term sedation with sevoflurane on lung, kidneys and blood coagulation in an in-vivo-model of a pulmonary-induced systemic inflammation.

• Applicant: Dr. Patrick Kellner
• Subject Area: Anaesthesiology ; Immunology
• Term: from 2012 to 2014
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 227991763

Concepts of analgosedation are extensively debated and complex as they adress a variety of therapeutic aims (analgesia, sedation, anxiolysis). Modern volatile anaesthetics seem to have advantages in daily routine compared to intravenous analgosedation with regard to a low metabolism, better controllability and an organ-protective potential. However, previous studies have mainly focused on the effect of short term application of inhalative anaesthetics as during the timecourse of anaesthesia. Currently, the use of volatile anaesthetics in intensive care units is a possible alternative to established intravenous analgosedation. Because of technical innovations and changes in the profile of requirements of analgosedation in intensive care it is essential to investigate safety aspects, the potential effect of organ protection, as well as possible immunmodulation of the long-term sedation with the volatile anaesthetic sevoflurane. For this purpose long-term sedation with sevoflurane will be elucidated in an animal model in pathogen-free, male wistar-rats with pulmonary induction of a systemic inflammation. Lung inflammation, influence on the renal function and the coagulation system will be assessed. In order to establish a long-term model, the experiments are planned for 96 hours. With regard to the lung and renal function, this should be verified by histology as well as laboratory test and molecular markers. The coagulation system should be described by clinical tests and surface receptors. The findings will help defining in detail the impact of this type of sedation not only on the inflammatory pattern and pulmonary function, but also on kidney function and blood coagulation, two systems, which possibly could be impaired upon exposure to sevoflurane for days. The current proposal will provide a profound knowledge about a long-term sedation in sepsis in-vivo and might allow translation of certain aspects into a setting in the patient, helping designing clinical trials within this topic.

• DFG Programme: Research Fellowships
• International Connection: Switzerland
• Host: Professorin Dr. Beatrice Beck-Schimmer