title: Flumazenil expedites recovery from sevoflurane/remifentanil anaesthesia when administered to healthy unpremedicated patients.
abstract: OBJECTIVE
  To investigate the hypothesis that 0.3 mg flumazenil administered to healthy unpremedicated patients at the end of deep surgical sevoflurane/remifentanil anaesthesia would expedite recovery. Flumazenil, an imidazobenzodiazepine derivative, antagonizes the hypnotic/sedative effects of benzodiazepines on γ-aminobutyric acid receptors. However, endogenous benzodiazepine ligands (endozepines) were isolated in mammalian tissues of individuals who had not received benzodiazepines.
  
  
  METHODS
  Twenty-four healthy unpremedicated patients, scheduled to undergo elective surgery requiring general anaesthesia, were randomly allocated to receive either a single dose of 0.3 mg flumazenil (n = 14) or placebo (n = 10) intravenously at the end of the surgical procedure just before the discontinuation of the volatile anaesthetic. After study drug administration, the authors compared various recovery parameters in the flumazenil and control groups.
  
  
  RESULTS
  Median time to spontaneous respiration, eye opening on verbal command, extubation and time to date of birth recollection was significantly shorter in the flumazenil group than in the control group [2.5 min (2.0-3.0) vs. 7.0 min (6.8-8.3), 3.4 min (3.0-4.0) vs. 8.1 min (6.9-10.2), 4.0 min (3.0-5.0) vs. 9.0 min (7.0-10.8) and 4.7 min (4.0-5.0) vs. 10.3 min (8.0-12.0), respectively].
  
  
  CONCLUSIONS
  Administration of a single dose of 0.3 mg flumazenil to healthy unpremedicated patients at the end of sevoflurane/remifentanil anaesthesia results in earlier emergence from anaesthesia and significantly expedites recovery. This could redefine the role of flumazenil in general anaesthesia, implicating endozepine-dependent mechanisms.
authors.affiliation: Anaesthesiology Department, Thriassio General Hospital - NHS, Attica, Greece. angykarakosta@gmail.com
authors.forename: Agathi
authors.initials: A
authors.lastname: Karakosta
authors.forename: Beatrice
authors.initials: B
authors.lastname: Andreotti
authors.forename: Chara
authors.initials: C
authors.lastname: Chapsa
authors.forename: Aikaterini
authors.initials: A
authors.lastname: Pouliou
authors.forename: Emmanouil
authors.initials: E
authors.lastname: Anastasiou
mesh_terms: D000328:Adult; D000368:Aged; D000762:Anesthesia Recovery Period; D018685:Anesthetics, Inhalation / Q000494:pharmacology; D018686:Anesthetics, Intravenous / Q000494:pharmacology; D004311:Double-Blind Method; D017558:Elective Surgical Procedures / Q000379:methods; D005260:Female; D005442:Flumazenil / Q000494:pharmacology*; D018757:GABA Modulators / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008738:Methyl Ethers / Q000494:pharmacology*; D008875:Middle Aged; D010880:Piperidines / Q000494:pharmacology*; D000077208:Remifentanil; D000077149:Sevoflurane
chemical_list: D018685:Anesthetics, Inhalation; D018686:Anesthetics, Intravenous; D018757:GABA Modulators; D008738:Methyl Ethers; D010880:Piperidines; D000077149:Sevoflurane; D005442:Flumazenil; D000077208:Remifentanil