Threshold hypnotic concentration of methohexitone

Abstract

Methohexitone was administered to 8 healthy adult volunteers as a microprocessor controlled infusion that generated 3 cycles of linearly increasing plasma levels with an anticipated slope of 0.2 microgram.ml-1.min-1. When a deep unconscious state was obtained, as indicated by burst suppression in the EEG, the infusion was stopped and then restarted when the volunteer was fully orientated. Frequent venous blood samples were obtained during and after the infusions to evaluate the threshold concentration at induced sleep and the return of orientation, at the loss and return of the eye lid reflex and corneal reflex, and the appearance and disappearance of EEG burst suppression patterns. From the first to the third infusion cycle only a slight and insignificant increase in the mean threshold concentrations was observed so the plasma levels were averaged over all three infusion cycles. The concentrations (microgram/ml) found were: asleep 3.39 and orientated 3.35, loss 4.42 and recurrence 4.32 of eye lid reflex, loss 6.51 and recurrence 5.18 of corneal reflex, and appearance 10.7 and disappearance 9.3 of burst suppression. Acute tolerance that would have led to a significant increase in threshold concentration from the first to the last infusion cycle was not demonstrated. If induced sleep and the appearance of EEG burst suppression are considered as clinical endpoints of anaesthesia, the therapeutic window of methohexitone covers a mean venous serum concentration range of 3.4 to 10.7 micrograms/ml.