title: The interaction between propofol and clonidine for loss of consciousness.
abstract: Clonidine premedication reduces the intraoperative requirement for opioids and volatile anesthetics. Clonidine also reduces the induction dose of IV anesthetics. There is no information, however, regarding the effect of oral clonidine premedication on the propofol blood concentrations required for loss of consciousness, and the interaction between propofol and clonidine. We randomly administered target effect-site concentrations of propofol ranging from 0.5 to 5. 0 microg/mL by using computer-assisted target-controlled infusion to 3 groups of healthy male patients: Control (n = 35), 2.5 microg/kg Clonidine (n = 36), and 5.0 microg/kg Clonidine (n = 36) groups. Nothing was administered to the Control group. Clonidine (2.5 or 5.0 microg/kg) was administered orally 90 min before the induction of anesthesia in the Clonidine groups. After equilibration between the blood and effect-site for 15 min, a verbal command to open their eyes was given two times to the patients. Arterial blood samples for analysis of the serum propofol and clonidine concentrations were taken immediately before verbal commands were given. Measured serum propofol concentrations in equilibrium with the effect-site at which 50% of the patients did not respond to verbal commands (EC50 for loss of consciousness) were determined by logistic regression. The EC50 +/- SE values in the Control, 2.5 microg/kg Clonidine, and 5.0 microg/kg Clonidine groups were 2.67 +/- 0.18, 1.31 +/- 0.12, and 0.91 +/- 0.13 microg/mL, respectively. The EC50 in the 2.5 and 5.0 microg/kg clonidine groups was significantly smaller than that in the Control group (P < 0.001). The use of a response surface modeling analysis indicated that there was an additive interaction between measured arterial propofol and clonidine concentrations in relation to loss of consciousness. These results indicate that propofol and clonidine act additively for loss of consciousness.
  
  
  CONCLUSIONS
  Oral clonidine 2.5 and 5.0 microg/kg premedication decreases the propofol concentration required for loss of consciousness.
authors.affiliation: Department of Anesthesia, Self Defense Force Central Hospital, Tokyo, Japan. higu-chi@ka2.so-net.ne.jp
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Higuchi
authors.forename: Yushi
authors.initials: Y
authors.lastname: Adachi
authors.forename: Albert
authors.initials: A
authors.lastname: Dahan
authors.forename: Erik
authors.initials: E
authors.lastname: Olofsen
authors.forename: Shinya
authors.initials: S
authors.lastname: Arimura
authors.forename: Tomohisa
authors.initials: T
authors.lastname: Mori
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Satoh
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000316:Adrenergic alpha-Agonists / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D000328:Adult; D018686:Anesthetics, Intravenous / Q000493:pharmacokinetics*; D003000:Clonidine / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D004347:Drug Interactions; D006801:Humans; D008297:Male; D008875:Middle Aged; D011229:Preanesthetic Medication; D015742:Propofol / Q000493:pharmacokinetics*; D014474:Unconsciousness
chemical_list: D000316:Adrenergic alpha-Agonists; D018686:Anesthetics, Intravenous; D003000:Clonidine; D015742:Propofol