Anesthetic and hemodynamic interactions of dexmedetomidine and fentanyl in dogs.
BACKGROUND
Anesthetic doses of dexmedetomidine (DMED), a highly selective alpha 2 agonist, are not well tolerated hemodynamically. The combination of an opioid with DMED might reduce the dosage requirements for each drug and thereby allow the same anesthetic depth to be achieved with lesser degrees of their individual side effects.


METHODS
Dogs were anesthetized with enflurane. One group (n = 5) received intravenous doses of DMED from 0.1 to 10 micrograms/kg. Two other groups of five dogs each received fentanyl 15 micrograms/kg plus 0.05 microgram.kg-1.min-1 or fentanyl 45 micrograms/kg plus 0.2 micrograms.kg-1.min-1. Thereafter, they received DMED doses of 0.03-3 micrograms/kg. After the effects of the last DMED dose were measured, atipamezole 0.3 mg/kg was infused intravenously and all measurements were repeated. Then, naloxone (1 mg/kg) was injected intravenously and a final set of measurements obtained. Anesthetic effects were assessed by determining enflurane minimum alveolar concentration (MAC). Hemodynamics and plasma fentanyl concentrations were measured at each determination of MAC.


RESULTS
DMED and fentanyl individually produced dose-related reductions of enflurane MAC. During the lower rate infusion of fentanyl (plasma fentanyl concentration 1.0 +/- 0.3 ng/ml), DMED reduced enflurane MAC more than could be attributed to a simple additive interaction. During the higher rate infusion of fentanyl (plasma fentanyl concentration 4.4 +/- 0.7 ng/ml), DMED reduced enflurane MAC to greater degrees than were achievable by fentanyl alone. DMED caused a dose-dependent increase in arterial pressure concomitantly with a decrease in cardiac output, and these changes were not modified by fentanyl. The bradycardia following DMED was augmented by fentanyl.


CONCLUSIONS
There was a positive interaction, additive or synergistic, between DMED and fentanyl with respect to their enflurane-sparing effects. The interaction allowed the same depth of anesthesia to be achieved by lower doses of all three drugs, potentially limiting the intensity of their individual side effects. However, the presence of fentanyl increased the degree of bradycardia induced by DMED.
Salmenperä
M T
MT
Department of Anesthesiology, Emory University School of Medicine, Atlanta, Georgia.
Szlam
F
F
Hug
C C
CC
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000777:Anesthetics / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004737:Enflurane / Q000378:metabolism / Q000494:pharmacology; D005283:Fentanyl / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D007093:Imidazoles / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology*; D020926:Medetomidine; D008954:Models, Biological; D009270:Naloxone / Q000494:pharmacology; D011650:Pulmonary Alveoli / Q000378:metabolism
D000317:Adrenergic alpha-Antagonists; D000777:Anesthetics; D007093:Imidazoles; C050701:atipamezole; D009270:Naloxone; D004737:Enflurane; D020926:Medetomidine; D005283:Fentanyl