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

Abstract

Objective: To determine the effects of low and high dose infusions of dexmedetomidine and a peripheral α₂-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 ºC, respectively. After baseline MAC determination, dogs were administered two incremental loading and infusion doses of either dexmedetomidine (1.5 μg kg^-1 then 1.5 μg kg^-1 hour^-1 and 4.5 μg kg^-1 then 4.5 μg kg^-1 hour^-1) or MK-467 (90 μg kg^-1 then 90 μg kg^-1 hour^-1 and 180 μg kg^-1 then 180 μg 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%.

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 α₂-adrenergic antagonist to inhalation anesthesia in dogs.

Keywords: MK-467; adrenergic α(2)-receptor antagonist; dexmedetomidine; dog; minimum alveolar concentration.