Flumazenil

Publication Title: 
Anesthesiology

Midazolam is an imidazobenzodiazepine with unique properties when compared with other benzodiazepines. It is water soluble in its acid formulation but is highly lipid soluble in vivo. Midazolam also has a relatively rapid onset of action and high metabolic clearance when compared with other benzodiazepines. The drug produces reliable hypnosis, amnesia, and antianxiety effects when administered orally, intramuscularly, or intravenously.

Author(s): 
Reves, J. G.
Fragen, R. J.
Vinik, H. R.
Greenblatt, D. J.
Publication Title: 
European Journal of Anaesthesiology. Supplement

Midazolam and alfentanil were infused in a totally i.v. anesthetic technique (TIVA) to patients undergoing hysterectomy. Correlations of midazolam plasma concentrations and effects were made during recovery. Due to the high doses of midazolam administered during TIVA, metabolism and not redistribution mainly governed the duration of effects post-infusion. The concomitant administration of alfentanil contributed to the sedative effect, as illustrated by a shift of the concentration-response curve to the left. As a result of these effects, recovery was prolonged and extended over 2-6 h.

Author(s): 
Nilsson, A.
Persson, M. P.
Hartvig, P.
Publication Title: 
Clinical Pharmacokinetics

Flumazenil (Ro 15-1788) is a specific benzodiazepine antagonist which can prevent or abolish selectively at the receptor level all centrally mediated effects of benzodiazepines. Following oral administration flumazenil is rapidly absorbed (peak concentrations are achieved after 20 to 90 minutes), but bioavailability is low (16%) due to significant presystemic elimination.

Author(s): 
Klotz, U.
Kanto, J.
Publication Title: 
British Journal of Anaesthesia

In a randomized, double-blind study, we administered placebo and flumazenil to 40 healthy Chinese boys, aged 3-12 yr, undergoing circumcision. The children received midazolam 0.5 mg kg-1 orally for premedication and 0.5 mg kg-1 i.v. during induction. After operation the patients were given 0.1 ml kg-1 of a blinded solution followed by 0.05 ml kg-1 min-1 until either they awoke or the 10-ml ampoule of solution was empty.

Author(s): 
Jones, R. D.
Lawson, A. D.
Andrew, L. J.
Gunawardene, W. M.
Bacon-Shone, J.
Publication Title: 
Minerva Anestesiologica
Author(s): 
Passavanti, M. B.
Consiglio, F.
De Lisio, C.
Finelli, B.
Iannotti, M.
Pace, M. C.
Publication Title: 
Anesthesia and Analgesia

Flumazenil, a benzodiazepine antagonist, clearly reverses midazolam-induced sedation; reversal of ventilatory depression has not been as well demonstrated. Thirty-two subjects completed this randomized, double-blind, placebo-controlled study investigating the dose-response relationship and duration of flumazenil's effects on ventilatory depression and hypnosis induced by a continuous midazolam infusion.

Author(s): 
Flögel, C. M.
Ward, D. S.
Wada, D. R.
Ritter, J. W.
Publication Title: 
Neurophysiologie Clinique = Clinical Neurophysiology

The effects of a pure benzodiazepine antagonist (Flumazenil) on the responses R1 and R2 of the blink reflex, psychomotor tests, and Event Related Potentials (ERP), in six healthy volunteers sedated with Midazolam have been compared. Measurements were made during each of four successive phases. Phase 0 corresponded to control recordings. Midazolam was administered rapidly during phase 1 and slowly during phase 2. Phase 3 corresponded to spontaneous waking once the administration of Midazolam had been stopped. Flumazenil was administered during phase 2.

Author(s): 
Hort-Legrand, C.
Catoire, P.
Métral, S.
Publication Title: 
Journal of Ethnopharmacology

Rubus brasiliensis hexanic fraction induced anxiolysis in rodents, which was reversed by flumazenil, a specific GABA(A)-benzodiazepine receptor antagonist (Nogueira et al., 1998a,b). Then, we investigated if this hexanic fraction was able to induce hypnotic, anticonvulsant and muscle relaxant effects, and the involvement of GABA(A)-system. The hexanic fraction (50, 100, 150 and 300 mg/kg, vo) was administered to male Swiss mice, 30 min before the tests.

Author(s): 
Nogueira, E.
Vassilieff, V. S.
Publication Title: 
Masui. The Japanese Journal of Anesthesiology

The present investigation dealt with the effect of simultaneous administration of flumazenil on the hypnotic activity of propofol using a behavioral model of ddY mice. The mixed solution of propofol and flumazenil was administered intravenously into the mice tail vein and the achievement of hypnosis was defined as the loss of the righting reflex. Flumazenil 0.2 mg.kg-1 significantly decreased the required dose of propofol for hypnosis (8.43 +/- 0.46 mg.kg-1) compared to the control group (10.55 +/- 0.55 mg.kg-1).

Author(s): 
Adachi, Y.
Watanabe, K.
Uchihashi, Y.
Higuchi, H.
Satoh, T.
Publication Title: 
Journal of Clinical Anesthesia

STUDY OBJECTIVE: To evaluate the effect of a small dose of midazolam (10 microg kg(-1)) on induction and emergence during short-term propofol anesthesia and to investigate the effects of subsequent administration of flumazenil. DESIGN: Double-blinded, prospective, randomized study. SETTING: Operating room of a medical college hospital. PATIENTS: 30 male ASA physical status I and II patients (ages 51 to 75) scheduled for minor surgery under spinal anesthesia.

Author(s): 
Adachi, Y. U.
Watanabe, K.
Higuchi, H.
Satoh, T.

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