Evaluation of a combination of alfaxalone and methadone, with or without midazolam, for premedication in healthy dogs

Introduction: The study objective was to evaluate sedative and physiologic effects of midazolam associated with a combination of methadone and alfaxalone for IM premedication in dogs. Methods: Sixteen healthy dogs of various breeds, weighing 5–12 kg, classified ASA status I-II, randomly received a combination of 0.5 mg kg−1 of methadone and 1 mg kg−1 of alfaxalone with (MMA) or without (MA) 0.5 mg kg−1 of midazolam by IM injection. Quality of sedation was assessed at 10, 15, 20 and 25 minutes post-injection, by an observer blinded to treatment. Cardiovascular, respiratory variables and additional intravenous alfaxalone required for endotracheal intubation were recorded. Data were analyzed with mixed-effect linear model on rank or Mann-Whitney rank-sum test (p≤0.05). Results: There was no significant difference over time in heart rate, respiratory rate, systolic blood pressure, SpO2 and temperature between MA and MMA premedication. Sedation increased over time (p < 0.01), however dogs premedicated with MMA appeared significantly less sedated than dogs premedicated with MA at 15 (p=0.02), 20 (p=0.02) and 25 minutes (p=0.01) post-injection. This was substantiated by the fact that dogs premedicated with MMA were almost four times more likely to show delirium than those premedicated with MA (OR 3.95, CI 0.69-7.21, p=0.02). The amount of alfaxalone needed for intubation did not differ between treatments (p=0.92). Conclusion: Results suggest that adding midazolam to an IM combination of methadone and alfaxalone does not improve sedation scores or amount of agent needed for intubation in healthy dogs.