Modern trends in the investigation of new hypnotics in anaesthesia.

Abstract

Over the last 20 years standardized techniques have been employed for the investigation of intravenous hypnotics, psychotropic and neuroleptic drugs. Sleep has been studied with the help of EEG measures and side-effects have been evaluated by psychometric tests. The EEG is a proven parameter with regard to dosage determination and as objective means to find sleep-inducing quantities of drugs. By means of vigilosomnograms we have established dose-effect curves and have made comparisons between related drugs in the form of equivalence studies. From an anaesthesiological point of view controllability of a substance is determined by duration of effect (short- or long-acting) and by depth of sleep (light or deep states) achieved. By these criteria midazolam displays good controllability with regard to duration, but not in terms of depth of sleep, since it follows the "all-or-nothing" rule, even with 0.1 mg/kg following both intravenous or intramuscular injection. Lormetazepam, on the other hand, shows good controllability of depth of sleep from tranquillity via sedation to hypnosis, but duration of effect is less well controllable in that patients remain lightly asleep even after 2 h. According to the vigilosomnograms the lormetazepam/oxygen/nitrous oxide combination produced a super-added increase in the depth of the hypnotic effect. After droperidol the specific nitrous oxide component of the depth of sleep at Bo stage was not exceeded. The development of benzodiazepine antagonists, which immediately counteract the benzodiazepine induced sleep and respiratory obstruction is a milestone in the area of CNS research.