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 α-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. PaCO and temperature were maintained at 40±5 mmHg (5.3±0.7 kPa) and 38±0.5 ºC, respectively. After baseline MAC determination, dogs were administered two incremental loading and infusion doses of either dexmedetomidine (1.5 μg kg then 1.5 μg kg hour and 4.5 μg kg then 4.5 μg kg hour) or MK-467 (90 μg kg then 90 μg kg hour and 180 μg kg then 180 μg kg hour); 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%.

Conclusions And Clinical 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 α-adrenergic antagonist to inhalation anesthesia in dogs.