title: Antagonistic effect of flumazenil after midazolam sedation on arterial-cardiac baroreflex.
abstract: BACKGROUND
  Flumazenil is generally administered to antagonise the sedative effect of midazolam. However, although flumazenil completely antagonises the sedative effect of midazolam, a few effects remain unantagonised. Hence, it is unclear whether flumazenil restores the attenuation of the arterial-cardiac baroreflex (i.e. arterial-heart rate reflex) induced by midazolam. We investigated the antagonistic effect of flumazenil administered after midazolam on cardiac baroreflex, to reveal whether complete recovery from midazolam-induced sedation by flumazenil administration is accompanied by restoration of midazolam's attenuating effects on the cardiac baroreflex.
  
  
  METHODS
  Twelve healthy male subjects received midazolam followed by flumazenil until complete recovery from midazolam sedation. Before and during midazolam sedation, and after flumazenil administration, cardiac baroreflex function was assessed by sequence analysis and transfer function analysis between spontaneous oscillations in systolic arterial pressure and R-R interval.
  
  
  RESULTS
  During midazolam sedation, defined by an Observer's Assessment of Alertness/Sedation scale score of 3, BIS value decreased significantly. Simultaneously, the baroreflex indices of the two analyses decreased significantly compared with baseline, suggesting attenuated cardiac baroreflex function. With complete recovery from midazolam sedation by flumazenil, indicated by an Observer's Assessment of Alertness/Sedation scale score of 5, BIS values returned to the baseline level. Simultaneously, cardiac baroreflex indices also returned to baseline levels.
  
  
  CONCLUSIONS
  The present results suggest that complete recovery from midazolam sedation by flumazenil is accompanied by restoration of the attenuated cardiac baroreflex function induced by midazolam.
authors.affiliation: Division of Anesthesiology, Department of Anesthesiology, Nihon University School of Medicine, Tokyo, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Ueda
authors.forename: Y
authors.initials: Y
authors.lastname: Ogawa
authors.forename: K
authors.initials: K
authors.lastname: Aoki
authors.forename: N
authors.initials: N
authors.lastname: Hirose
authors.forename: D
authors.initials: D
authors.lastname: Gokan
authors.forename: J
authors.initials: J
authors.lastname: Kato
authors.forename: S
authors.initials: S
authors.lastname: Ogawa
authors.forename: K
authors.initials: K
authors.lastname: Iwasaki
mesh_terms: D000328:Adult; D017704:Baroreflex / Q000187:drug effects*; D004562:Electrocardiography / Q000187:drug effects; D004569:Electroencephalography / Q000187:drug effects; D005442:Flumazenil / Q000494:pharmacology*; D006801:Humans; D006993:Hypnotics and Sedatives / Q000037:antagonists & inhibitors*; D008297:Male; D008874:Midazolam / Q000037:antagonists & inhibitors*; D013599:Systole / Q000187:drug effects
chemical_list: D006993:Hypnotics and Sedatives; D005442:Flumazenil; D008874:Midazolam