Experiment 1: the anaesthesia experiment
Participants were randomised to receive either dexmedetomidine (Design of Experiments 1 and 2. (a) Anaesthesia experiment. R1, first regaining of responsiveness; R2, second regaining of responsiveness; R3, recovery to responsiveness; UR1, first period of unresponsiveness; UR2, second period of unresponsiveness; UR3, third period of unresponsiveness with higher drug concentration level. (b) Sleep experiment. N1, NREM sleep stage N1; N2, NREM sleep stage N2; N3, NREM sleep stage N3. NREM, non-rapid eye movement; PET, positron emission tomography.Participant responsiveness was tested using an auditory responsiveness test (Interview questions and content analysis scale.Participants were then left unstimulated, and if they achieved a second unresponsive (UR2) period with the same drug concentration as in UR1/R1, the procedure was repeated. Finally, the drug concentration was increased by 50% to achieve a third period of unresponsiveness with a higher drug concentration level (UR3). The mean targeted doses for UR3 were 2.38 (1.05) ng mlBlood samples for drug concentration measurements were drawn at baseline, at the end of each drug target infusion step, and when the responsiveness of the participant changed during the steady infusion or after the infusion was terminated. Dexmedetomidine concentrations in plasma were measured by high-performance liquid chromatography (HPLC) with tandem mass spectrometry, and propofol concentrations were measured by HPLC with fluorescence detection.