Absence of agonist effects of high-dose flumazenil on ventilation and psychometric performance in human volunteers.

Abstract

Flumazenil, a specific benzodiazepine antagonist, reverses sedative and respiratory depressant effects of benzodiazepines. We determined whether a large dose of flumazenil, injected alone, induces respiratory depression or alteration of psychomotor performance. After informed consent, eight healthy volunteers participated at three different sessions: 1) flumazenil (0.1 mg/kg) (a dose 7-15 times the clinically recommended dose) injected intravenously over a 5-min period, followed by placebo (NaCl 0.9%); 2) flumazenil at the same dose and injection rate as in Session 1, followed by midazolam (0.1 mg/kg) injected over 5 min; and 3) placebo followed by midazolam at the same dose as above and administered over 5 min. All drug combinations were administered in a randomized and double-blind manner. Tidal volume, respiratory frequency, minute ventilation, and mean inspiratory flow were continuously measured from 15 min before until 120 min after drug injection by noninvasive on-line data acquisition methods. Psychometric performance was evaluated 15 min before the first drug and 15 min after administration of the second drug. During the placebo-midazolam session, tidal volume (-40%), minute ventilation (-25%), and inspiratory flow (-25%) were significantly (P < 0.01) decreased compared both with baseline and with the other two sessions, and psychometric performance was significantly (P < 0.01) altered; in contrast, there was no significant change in any of the measured respiratory or psychometric variables during the flumazenil-placebo or flumazenil-midazolam sessions. We conclude that flumazenil, administered at about 10 times the clinically recommended dose, has no agonist effects on resting ventilation or psychomotor performance in normal subjects.

• Authors: A Forster, G Crettenand, C E Klopfenstein, D R Morel
• Journal: Anesthesia and analgesia (Anesth Analg) Vol. 77 Issue 5 Pg. 980-4 (Nov 1993) ISSN: 0003-2999 [Print] United States
• PMID: 8214737 (Publication Type: Clinical Trial, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Flumazenil
• Midazolam

Topics

• Adult
• Depression, Chemical
• Double-Blind Method
• Flumazenil (administration & dosage)
• Humans
• Injections, Intravenous
• Male
• Midazolam (administration & dosage)
• Psychomotor Performance (drug effects, physiology)
• Reference Values
• Respiration (drug effects, physiology)