[Hypnotically active blood level of midazolam].
Midazolam was administered to seven healthy adult volunteers by microprocessor controlled infusions that generated 3 cycles of lineary increasing plasma levels with an anticipated slope of 20 ng ml-1 min-1. When a deep unconscious status was obtained as indicated by no response to loud verbal stimuli, the concentrations were kept constant at that plateau for 30 min. Thereafter, the infusions were stopped and restarted when the volunteers were again fully responsive to acoustic stimuli of normal intensity. Frequent venous blood samples were obtained during and after the infusions to evaluate venous threshold concentrations of induced sleep and recurrence of orientation, loss and recurrence of eyelid-reflex (and corneal reflex), and unconsciousness and recovery of responsiveness to loud verbal stimuli. From the first to the third infusion cycle a slight, but not significant increase of mean threshold concentrations could be observed. Hence, they were averaged over all infusion cycles. In detail, the following concentrations (in ng/ml; mean +/- SD) resulted: asleep: 251 +/- 110 and oriented: 277 +/- 107, loss: 543 +/- 173 and recurrence of eye-lid reflex: 532 +/- 120, unconsciousness: 575 +/- 128 and recovery to responsiveness: 555 +/- 151. In all but one volunteer, the corneal reflex could be triggered at any time. Hence, a mean threshold concentration of that, observation could not be obtained. Phenomena of acute tolerance that should lead to significant increases of threshold concentrations from the first to the last infusion cycle could not be demonstrated.
D000328:Adult; D001143:Arousal / Q000187:drug effects*; D003243:Consciousness / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007260:Infusion Pumps; D008874:Midazolam / Q000097:blood* / Q000494:pharmacology; D012025:Reflex, Pupillary / Q000187:drug effects
D008874:Midazolam
Hypnotisch wirksame Blutspiegel von Midazolam.