title: Clonidine-ephedrine combination reduces pain on injection of propofol and blunts hemodynamic stress responses during the induction sequence.
abstract: OBJECTIVE
  To evaluate the effects of clonidine and ephedrine on propofol-induced pain and on hemodynamic changes during the induction sequence.
  
  
  METHODS
  This was a prospective, randomized, double-blind study.
  
  
  METHODS
  The study was conducted at a university hospital.
  
  
  METHODS
  200 ASA physical status I or II adult patients scheduled for elective surgery.
  
  
  METHODS
  Patients were randomly allocated to one of 4 groups (50 patients per group): clonidine-ephedrine (CE), clonidine-saline (CS), diazepam-ephedrine (DE), and diazepam-saline (DS). Thirty seconds after the administration of ephedrine or saline, propofol 2 mg/kg was infused at a rate of 18.3 mL/min.
  
  
  METHODS
  Patients were asked whether they had pain due to propofol injection. A blinded investigator evaluated the pain score: 0 = no pain, 1 = mild pain, 2 = severe pain without behavioral signs such as grimace or arm withdrawal movement, and 3 = severe pain accompanied by behavioral signs. Mean arterial blood pressure (MAP) and heart rate (HR) were measured at 1-minute intervals from just before the administration of ephedrine or saline to 5 minutes after the tracheal intubation.
  
  
  RESULTS
  Median pain score in CE was significantly lower than those in the other groups (P < 0.0001). Pain scores in CS and DE were significantly lower than that in DS (P < 0.05). Ephedrine increased HR in CE and DE (P < 0.05), but clonidine did not augment the effect. Mean arterial blood pressure before tracheal intubation decreased to comparable values in all groups. After the intubation, mean arterial blood pressure and HR in CE and CS were significantly lower than those in DE and DS (P < 0.05).
  
  
  CONCLUSIONS
  Combination of clonidine and ephedrine effectively reduced propofol-induced pain, but did not prevent propofol-induced hypotension. Clonidine did not augment low dose of ephedrine-induced increase in HR and produced stable hemodynamic condition during the induction sequence.
authors.affiliation: Department of Anesthesiology, Faculty of Medicine, University of Yamanashi, Japan. ishiyama@yamanashi.ac.jp
authors.forename: Tadahiko
authors.initials: T
authors.lastname: Ishiyama
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kashimoto
authors.forename: Takeshi
authors.initials: T
authors.lastname: Oguchi
authors.forename: Atsushi
authors.initials: A
authors.lastname: Furuya
authors.forename: Hisashi
authors.initials: H
authors.lastname: Fukushima
authors.forename: Teruo
authors.initials: T
authors.lastname: Kumazawa
mesh_terms: D000700:Analgesics / Q000494:pharmacology*; D018686:Anesthetics, Intravenous / Q000009:adverse effects*; D003000:Clonidine / Q000494:pharmacology*; D004809:Ephedrine / Q000494:pharmacology*; D005260:Female; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010146:Pain / Q000139:chemically induced / Q000188:drug therapy*; D015742:Propofol / Q000009:adverse effects*; D011446:Prospective Studies; D013312:Stress, Physiological / Q000188:drug therapy*
chemical_list: D000700:Analgesics; D018686:Anesthetics, Intravenous; D004809:Ephedrine; D003000:Clonidine; D015742:Propofol