title: Dexmedetomidine, a selective alpha 2-agonist, does not potentiate the cardiorespiratory depression of alfentanil in the rat.
abstract: The authors examined the cardiovascular and respiratory effects of the highly selective alpha 2-adrenergic agonist dexmedetomidine, both alone and in combination with the synthetic opiate alfentanil. Spontaneously ventilating rats (n = 28) were pretreated with dexmedetomidine, 10 or 30 micrograms/kg; dexmedetomidine, 30 micrograms/kg in combination with the central-acting alpha 2-antagonist idazoxan, 10 mg/kg; or vehicle. Fifteen minutes later all rats received alfentanil, 500 micrograms/kg. Pretreatment with dexmedetomidine reduced heart rate in a dose-related fashion. Administration of alfentanil also caused a significant reduction in heart rate. However, following alfentanil, the dexmedetomidine-treated animals did not have significantly greater bradycardia than control animals. An increase in blood pressure was observed in those animals receiving the larger dose of dexmedetomidine, but this difference disappeared following injection of alfentanil. The addition of idazoxan to the pretreatment regimen prevented the changes seen with dexmedetomidine. Pretreatment with dexmedetomidine produced no significant changes in arterial pH or PCO2. In all groups, administration of alfentanil resulted in a decrease in arterial pH that ultimately became a mixed respiratory and metabolic acidosis. The acidosis promptly resolved following injection of naloxone (1 mg/kg). It appears that dexmedetomidine, at the doses given, has little or no effect on respiration. Dexmedetomidine decreases heart rate but does not add to bradycardia following alfentanil. There is a hypertensive effect seen at the higher dose of dexmedetomidine, but this effect disappears when the drug is given in conjunction with alfentanil. These data show that addition of the alpha 2-agonist dexmedetomidine will not worsen the cardiovascular and respiratory depression associated with high-dose opiates in the spontaneously ventilating rat.
authors.affiliation: Department of Anesthesiology, University of California, San Diego School of Medicine.
authors.forename: S R
authors.initials: SR
authors.lastname: Furst
authors.forename: M B
authors.initials: MB
authors.lastname: Weinger
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D015760:Alfentanil / Q000494:pharmacology*; D000818:Animals; D004146:Dioxanes / Q000494:pharmacology; D004347:Drug Interactions; D006439:Hemodynamics / Q000187:drug effects*; D019329:Idazoxan; D007093:Imidazoles / Q000494:pharmacology*; D008297:Male; D020926:Medetomidine; D051381:Rats; D011919:Rats, Inbred Strains; D012119:Respiration / Q000187:drug effects*
chemical_list: D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D004146:Dioxanes; D007093:Imidazoles; D015760:Alfentanil; D020926:Medetomidine; D019329:Idazoxan