Ventilatory effects of dexmedetomidine, atipamezole, and isoflurane in dogs.
Dexmedetomidine (DMED) is a novel alpha 2 adrenergic agonist that has been shown to have potent analgesic and anesthetic sparing effects. This study was designed to investigate the effects of DMED, both alone and combined with isoflurane, on resting ventilation, the hypercapnic response, and the hypoxic response in dogs. When given alone, 1 microgram/kg decreased resting ventilation by 22% but at larger doses (10, 20, and 100 micrograms/kg) resting ventilation increased, doubling at 100 micrograms/kg. Doses of 10 micrograms/kg and greater caused a maximum depression of 60% in the slope of the hypercapnic response, but no dose had a significant effect on the hypoxic ventilatory response. A dose of 3 micrograms/kg of DMED reduced isoflurane MAC from 1.3% to 0.37%, and the ventilatory effects of this 1 MAC combination were intermediate between the awake values and those of isoflurane-anesthetized (1.3%) dogs. Atipamezole is a specific centrally acting alpha 2 receptor antagonist and when given with DMED in isoflurane-anesthetized dogs prevented the ventilatory depression. However, atipamezole alone also ventilatory stimulating effects, which may indicate tonic alpha 2 adrenergic activity. The ventilatory depression caused by DMED, either alone or combined with isoflurane, at doses that significantly reduce anesthetic requirements are relatively mild.
University of California Los Angeles School of Medicine, Department of Anesthesiology 90024-1778.
D
D
Nguyen
I
I
Abdul-Rasool
D
D
Ward
J
J
Hsieh
D
D
Kobayashi
S
S
Hadlock
F
F
Singer
B
B
Bloor
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D006935:Hypercapnia / Q000139:chemically induced / Q000378:metabolism; D007093:Imidazoles / Q000008:administration & dosage / Q000494:pharmacology*; D007530:Isoflurane / Q000032:analysis / Q000494:pharmacology*; D020926:Medetomidine; D012119:Respiration / Q000187:drug effects*
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D007093:Imidazoles; C050701:atipamezole; D007530:Isoflurane; D020926:Medetomidine