[Impairment of the cognitive faculties and the reaction capability caused by midazolam despite reversal using flumazenil].
Imidazobenzodiazepine (flumazenil) is a specific competitive benzodiazepine antagonist. It antagonizes the sedative-hypnotic, anticonvulsive, anxiolytic and the muscle-relaxant effects of benzodiazepines. Its efficacy is prompt and complete. In several studies rebound phenomena have been observed. It was the aim of this randomized double blind study to investigate the efficacy of flumazenil by psychometric tests. The psychometric parameters we used were cognition and choice reaction time of 12 young and healthy volunteers. Three medication groups (A, B and C) were formed for this investigation. In a cross over design all volunteers had to be treated in each of these three medication groups. Between the groups we set a test-free interval of 7 days for every volunteer. In medication group A (midazolam/flumazenil) we applied 15 mg midazolam. Reversion was performed after 60 min with 0.5 mg flumazenil. In medication group B (placebo/flumazenil) midazolam was replaced by a physiological solution of sodium chloride. In medication group C (placebo/placebo) midazolam and flumazenil were substituted by a physiological solution of sodium chloride. For the investigation of the psychometric parameters (cognition and choice reaction time) we used the so called syndrome kurz test (SKT) and the decision reaction time measuring instrument ("Entscheidungs-Reaktionszeit-Messgerät"; ERM). Psychometric investigations were performed in all groups at intervals of 5, 30, 60, 90, 120, 180 and 240 min. Our results show that cognitive abilities remain impaired up to 60 min after the administration of flumazenil. Decision time and choice reaction time improved 120 min after administration of the antagonist. In our investigation neither rebound phenomena nor agonistic reactions of flumazenil were observed.(ABSTRACT TRUNCATED AT 250 WORDS)
Schlager
A
A
Klinik für Anaesthesie und Allgemeine Intensivmedizin, Universität Innsbruck.
Morawetz
R F
RF
Huber
C
C
Furtwängler
W
W
Luger
T J
TJ
Schreithofer
D
D
D000328:Adult; D003071:Cognition / Q000187:drug effects*; D004311:Double-Blind Method; D005260:Female; D005442:Flumazenil / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008874:Midazolam / Q000037:antagonists & inhibitors*; D011930:Reaction Time / Q000187:drug effects*
D005442:Flumazenil; D008874:Midazolam