title: Dexmedetomidine premedication attenuates ketamine-induced cardiostimulatory effects and postanesthetic delirium.
abstract: BACKGROUND
  Dexmedetomidine is a new potent and highly selective alpha 2-adrenoceptor agonist with sedative-hypnotic and anesthetic sparing properties. Because of its sympathoinhibitory activity, it may prove useful in balancing the cardiostimulatory effects and attenuating the adverse central nervous system effects of ketamine.
  
  
  METHODS
  A double-blind, randomized and comparative parallel-group study design was employed in 40 volunteers with ASA physical status 1 who were scheduled for elective superficial surgery under ketamine anesthesia. Dexmedetomidine (2.5 micrograms/kg, n = 20) or midazolam (0.07 mg/kg, n = 20) was administered intramuscularly 45 min before induction of anesthesia. Anesthesia was induced with 2 mg/kg ketamine intravenously, and muscle relaxation was achieved with vecuronium. After tracheal intubation, anesthesia was maintained with nitrous oxide/oxygen (2:1) and additional 1 mg/kg intravenous ketamine boluses according to clinical and cardiovascular criteria. Hypotension and bradycardia were treated by increasing the intravenous infusion rate of crystalloids and intravenous atropine, respectively. Sedative and anxiolytic properties, intra- and postoperative drug requirements, psychomotor and cognitive impairments, and cardiovascular effects were compared between the two groups.
  
  
  RESULTS
  Dexmedetomidine and midazolam proved to have equal sedative and anxiolytic effects after intramuscular administration, but dexmedetomidine induced significantly less preoperative psychomotor impairment and less anterograde amnesia than did midazolam. Compared to midazolam, dexmedetomidine decreased the need for intraoperative ketamine and was more effective in reducing ketamine-induced adverse central nervous system effects. Dexmedetomidine also was superior to midazolam in attenuating the hemodynamic responses to intubation and the cardiostimulatory effects of ketamine in general, but it increased the incidence of intra- and postoperative bradycardia.
  
  
  CONCLUSIONS
  These results suggest that premedication with 2.5 micrograms/kg dexmedetomidine is effective in attenuating the cardiostimulatory and postanesthetic delirium effects of ketamine. However, because of its propensity to cause bradycardia, routine use of an anticholinergic drug should be considered.
authors.affiliation: Department of Anesthesiology, Central Military Hospital, Helsinki, Finland.
authors.forename: J
authors.initials: J
authors.lastname: Levänen
authors.forename: M L
authors.initials: ML
authors.lastname: Mäkelä
authors.forename: H
authors.initials: H
authors.lastname: Scheinin
mesh_terms: D000293:Adolescent; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000328:Adult; D001794:Blood Pressure / Q000187:drug effects*; D003693:Delirium / Q000517:prevention & control*; D004311:Double-Blind Method; D006339:Heart Rate / Q000187:drug effects*; D006801:Humans; D006993:Hypnotics and Sedatives / Q000494:pharmacology*; D007093:Imidazoles / Q000494:pharmacology*; D007649:Ketamine / Q000009:adverse effects*; D020926:Medetomidine; D008874:Midazolam / Q000494:pharmacology; D011229:Preanesthetic Medication; D012119:Respiration / Q000187:drug effects; D013268:Stimulation, Chemical
chemical_list: D000316:Adrenergic alpha-Agonists; D006993:Hypnotics and Sedatives; D007093:Imidazoles; D007649:Ketamine; D020926:Medetomidine; D008874:Midazolam