Nitrous Oxide - Sevoflurane-Remifentanil Interaction: Multiple Response Surfaces, Validation of Calibration Stimuli, Validation of the Intraoperative Isobole Concept and Investigating Remifentanil Induced Opioid Tolerance.

patients are allocated to one of the two study groups.

In both groups a mixture of 60% nitrous oxide and 40% oxygen is administered through a face mask. In the first group the patient receives a constant concentration of sevoflurane. In this group the remifentanil concentration will be injected via an intravenous line in a step up protocol. In the second group remifentanil is injected in a fixed rate and sevoflurane is administered in a step up concentration.

During the study, at predefined times, we will assess different levels of sedation (OAA/S score) and the reaction on tetanic stimulation of the ulnar nerve, insertion of a laryngeal mask airway and laryngoscopy. In addition heart rate, SpO2 and capnography will be recorded continuously and non invasive bloodpressure will be recorded using a 1 minute interval time. Spectral entropy and BIS derived from the frontal EEG will be used to monitor clinical cerebral drug effect.

The null hypothesis is that remifentanil lowers the concentration of sevoflurane dissolved in a mixture of 60% nitrous oxide and 40% oxygen to (1) tolerate a specific stimulation and to (2) obtain a certain electroencephalographic parameter value and vice versa. Additionally the results of this study will be compared with a former interaction study of the same study group that did not involve nitrous oxide, in order to depict the shift in the response surface evoked by nitrous oxide.