Effects of methadone on the minimum alveolar concentration of isoflurane in dogs

Objective To investigate the effects of methadone on the minimum alveolar concentration of isoflurane (ISO(MAC)) in dogs.Study design Prospective, randomized cross-over experimental study.Animals Six adult mongrel dogs, four males and two females, weighing 22.8 +/- 6.6 kg.Methods Animals were anesthetized with isoflurane and mechanically ventilated on three separate days, at least 1 week apart. Core temperature was maintained between 37.5 and 38.5 degrees C during ISO(MAC) determinations. on each study day, ISO(MAC) was determined using electrical stimulation of the antebrachium (50 V, 50 Hz, 10 mseconds) at 2.5 and 5 hours after intravenous injection of physiological saline (control) or one of two doses of methadone (0.5 or 1.0 mg kg(-1)).Results Mean (+/- SD) ISO(MAC) in the control treatment was 1.19 +/- 0.15% and 1.18 +/- 0.15% at 2.5 and 5 hours, respectively. The 1.0 mg kg(-1) dose of methadone reduced ISO(MAC) by 48% (2.5 hours) and by 30% (5 hours), whereas the 0.5 mg kg(-1) dose caused smaller reductions in ISO(MAC) (35% and 15% reductions at 2.5 and 5 hours, respectively). Both doses of methadone decreased heart rate (HR), but the 1.0 mg kg(-1) dose was associated with greater negative chronotropic actions (HR 37% lower than control) and mild metabolic acidosis at 2.5 hours. Mean arterial pressure increased in the MET1.0 treatment (13% higher than control) at 2.5 hours.Conclusions and clinical relevance Methadone reduces ISO(MAC) in a dose-related fashion and this effect is lessened over time. Although the isoflurane sparing effect of the 0.5 mg kg(-1) dose of methadone was smaller in comparison to the 1.0 mg kg(-1) dose, the lower dose is recommended for clinical use because it results in less evidence of cardiovascular impairment.