Effects of constant rate infusions of dexmedetomidine or MK-467 on the minimum alveolar concentration of sevoflurane in dogs

Objective To determine the effects of low and high dose infusions of dexmedetomidine and a peripheral alpha(2)-adrenoceptor antagonist, MK-467, on sevoflurane minimum alveolar concentration (MAC) in dogs. Study design Crossover experimental study. Animals Six healthy, adult Beagle dogs weighing 12.6 +/- 0.9 kg (mean +/- standard deviation). Methods Dogs were anesthetized with sevoflurane in oxygen. After a 60-minute instrumentation and equilibration period, the MAC of sevoflurane was determined in triplicate using the tail clamp technique. PaCO2 and temperature were maintained at 40 +/- 5 mmHg (5.3 +/- 0.7 kPa) and 38 +/- 0.5 degrees C, respectively. After baseline MAC determination, dogs were administered two incremental loading and infusion doses of either dexmedetomidine (1.5 mu g kg(-1) then 1.5 mu g kg(-1) hour(-1) and 4.5 mu g kg(-1) then 4.5 mu g kg(-1) hour(-1)) or MK-467 (90 mu g kg(-1) then 90 mu g kg(-1) hour(-1) and 180 mu g kg(-1) then 180 mu g kg(-1) hour(-1)); loading doses were administered over 10 minutes. MAC was redetermined in duplicate starting 30 minutes after the start of drug administration at each dose. End-tidal sevoflurane concentrations were corrected for calibration and adjusted to sea level. A repeated-measures analysis was performed and comparisons between doses were conducted using Tukey's method. Statistical significance was considered at p < 0.05. Results Sevoflurane MAC decreased significantly from 1.86 +/- 0.3% to 1.04 +/- 0.1% and 0.57 +/- 0.1% with incremental doses of dexmedetomidine. Sevoflurane MAC significantly increased with high dose MK-467, from 1.93 +/- 0.3% to 2.29 +/- 0.5%. Conclusionsandclinical relevance Dexmedetomidine caused a dose-dependent decrease in sevoflurane MAC, whereas MK-467 caused an increase in MAC at the higher infusion dose. Further studies evaluating the combined effects of dexmedetomidine and MK-467 on MAC and cardiovascular function may elucidate potential benefits of the addition of a peripheral alpha(2)-adrenergic antagonist to inhalation anesthesia in dogs.