title: The Effects of Flumazenil After Midazolam Sedation on Cerebral Blood Flow and Dynamic Cerebral Autoregulation in Healthy Young Males.
abstract: BACKGROUND
  It is unknown whether flumazenil antagonizes the decrease in cerebral blood flow or the alteration in dynamic cerebral autoregulation induced by midazolam. We, therefore, investigated the effects on cerebral circulation of flumazenil administered after midazolam, to test our hypothesis that, along with complete reversal of sedation, flumazenil antagonizes the alterations in cerebral circulation induced by midazolam.
  
  
  METHODS
  Sixteen healthy young male subjects received midazolam followed by flumazenil. The modified Observer's Assessment of Alertness/Sedation (OAA/S) scale and bispectral index (BIS) were used to assess levels of sedation/awareness. For evaluation of cerebral circulation, steady-state mean cerebral blood flow velocity (MCBFV) was measured by transcranial Doppler ultrasonography. In addition, dynamic cerebral autoregulation was assessed by spectral and transfer function analysis between mean arterial pressure (MAP) variability and MCBFV variability.
  
  
  RESULTS
  During midazolam sedation, defined by an OAA/S score of 3 (responds only after name is called loudly and/or repeatedly), BIS, steady-state MAP, steady-state CBFV, and transfer function gain decreased significantly compared with baseline. After flumazenil administration, an OAA/S score of 5 (responds readily to name spoken in a normal tone) was confirmed. Then, BIS and MAP returned to the same level as baseline. However, steady-state MCBFV showed a further significant decrease compared with that under midazolam sedation, and the decreased transfer function gain persisted.
  
  
  CONCLUSIONS
  Contrary to our hypothesis, the present results suggest that despite complete antagonism of the sedative effects of midazolam, flumazenil would not reverse the alterations in cerebral circulation induced by midazolam.
authors.affiliation: Departments of *Social Medicine, Division of Hygiene †Anesthesiology, Division of Anesthesiology, Nihon University School of Medicine, Tokyo, Japan.
authors.forename: Yojiro
authors.initials: Y
authors.lastname: Ogawa
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Iwasaki
authors.forename: Ken
authors.initials: K
authors.lastname: Aoki
authors.forename: Ryo
authors.initials: R
authors.lastname: Yanagida
authors.forename: Kaname
authors.initials: K
authors.lastname: Ueda
authors.forename: Jitsu
authors.initials: J
authors.lastname: Kato
authors.forename: Setsuro
authors.initials: S
authors.lastname: Ogawa
mesh_terms: D000328:Adult; D062186:Arterial Pressure / Q000187:drug effects; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D016292:Procedural Sedation; D056805:Consciousness Monitors; D004569:Electroencephalography; D005442:Flumazenil; D018757:GABA Modulators; D064368:Healthy Volunteers; D006706:Homeostasis / Q000187:drug effects*; D006801:Humans; D006993:Hypnotics and Sedatives; D008297:Male; D008874:Midazolam; D015656:Respiratory Mechanics / Q000187:drug effects; D017585:Ultrasonography, Doppler, Transcranial; D055815:Young Adult
chemical_list: D018757:GABA Modulators; D006993:Hypnotics and Sedatives; D005442:Flumazenil; D008874:Midazolam