Propofol was administered for 2 h to 11 volunteers by an adaptive feedback control algorithm based on quantitative EEG analysis. Median EEG frequency served as the control variable. The range 2-3 Hz was chosen as the target range of control. During the feedback period, volunteers did not respond to commands and eyelash reflex was abolished. An average median frequency of 2.5 (SD 0.3) Hz was obtained by administering propofol 1452 (262) mg within 2 h. Time to recovery was 17.9 (8.0) min. Compared with a study with methohexitone using the same approach, the relative potency of propofol was 0.72. The mean recovery time was less than half that observed after methohexitone.

A combined pharmacokinetic and pharmacodynamic model of methohexital was used to establish and evaluate feedback control of methohexital anesthesia in 13 volunteers. The median frequency of the EEG power spectrum served as the pharmacodynamic variable constituting feedback. Median frequency values from 2–3 Hz were chosen as the desired EEG level (set-point). In 11 volunteers, the feedback system succeeded in maintaining a satisfactory depth of anesthesia (i.e., unresponsiveness to verbal commands and tactile stimuli). During feedback control, 75% of all measured median frequency values were in the preset range of 2–3 Hz. This distribution of median frequency was obtained by applying random stimulation (six different acoustic and tactile stimuli) to the volunteers approximately every 1.5 min. The decrease of median frequency from baseline to anesthetic values was primarily induced by increasing the fractional power in the frequency band of 0.5–2 Hz from 12.6 ± 4.5% (mean ± SD) to 46.0 ± 2.5%. The median time to recovery (as defined by opening eyes on command) after cessation of the feedback control period was 20.6 min (10.7–44.5 min) when median EEG frequency was 5.2 Hz (4.7–8.4 Hz). The average requirement of methohexital (mean ± SD) during the 2 h was 1.02 ± 0.16 g. It is concluded that pharmacokinetic-pharmacodynamic models of intravenous anesthetics established previously may be used to form a suitable background for model-based feedback control of anesthesia by quantitative EEG analysis. This approach gives a possible solution to the problem of adapting pharmacokinetic and pharmacodynamic data to individuals when using population mean data as starting values for drug therapy.

SummaryThe combination of propofol and alfentanil was administered to 20 0.34). The plasma level of alfentanil was 285 nglml ( S D 72) during major noxious stimulation and 148 nglml ( S D 56) during riiinor stimulation. The computer-assisted infusions showed a measuredlpredicted ratio of I .01 ( S D

In 14 patients undergoing elective surgery the EEG was studied during anaesthesia with isoflurane and nitrous oxide (in oxygen) at 1.3 and 1.5 MAC. The distribution of spectral EEG indices of the baseline EEG, during the intraoperative and recovery periods were established and compared. Median frequency exhibited the most clear separation between the distributions during recovery and the intraoperative period. During anaesthesia, the median values were found to be lower than 5 Hz; when the patient was conscious, the EEG median frequency values were greater than 6 Hz. Time to recovery was 13.4 +/- 2.9 min and 30.0 +/- 8.5 min for the groups treated with 1.3 and 1.5 MAC, respectively. Burst suppression was observed during the loading period in all patients treated with 1.5 MAC and in five patients out of seven receiving 1.3 MAC. The average duration of the period of burst suppression was markedly greater in the group receiving 1.5 MAC than in the group receiving 1.3 MAC. It is concluded that devices designed for EEG trend monitoring during anaesthesia should preferably depict a frequency measure, and allow for burst suppression recognition before spectral analysis.

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