Fig. 1.
Schematic presentation of the study design. The drug infusion was started at concentration of 1.0 ng/ml for dexmedetomidine or 1.0 μg/ml for propofol, followed first by a 0.5 concentration increase and 0.25 increases thereafter until loss of responses to auditory stimuli (responsiveness test), defined as loss of responsiveness (LOR). Responsiveness tests are indicated by solid black (signifying responsiveness) or gray arrows (signifying unresponsiveness). Sedative but responsive levels (SED-n-SED) are indicated in reverse numerical order, SED representing the last responsive state before LOR. After achieving LOR, auditory stimuli were presented (to study event related potentials), accounting for the relatively long LOR period(s). At the end of the stabile period, an attempt was made to arouse the subjects during the constant drug infusion to achieve return of responsiveness (ROR). After ROR, the subject was left unstimulated, to regain the unresponsive state (LOR2). The second cycle was conducted in an identical manner, with a second awakening at the end (ROR2). After ROR2 (or an unsuccessful awakening), the target concentration was increased to 1.5 × LOR concentration to reach presumable loss of consciousness (LOC). Again, auditory stimuli were presented. Finally, the drug infusion was terminated and a continuous responsiveness test was presented until a spontaneous response was detected (third return of responsiveness, ROR3). A continuous electroencephalogram recording was performed throughout the study session and the segments selected for spectral analyses have been visualized with diamonds. Syringe symbols indicate venous blood samples drawn for drug concentration analysis. Horizontal gray bars indicate auditory stimuli (event related potentials; to be reported separately) and vertical bars interviews of subjective experiences (to be reported separately). EC = eyes closed; EO = eyes open.