Haemodynamic interactions of medetomidine and the peripheral alpha-2 antagonist MK-467 during step infusions in isoflurane-anaesthetised dogs

• The haemodynamic interactions of medetomidine (MED) step infusion with MK-467 (MK) step infusion were compared with MED alone in eight isoflurane-anaesthetised Beagle dogs in a randomised crossover study.
• MED infusion alone increased SAP, MAP and a-vO2 diff and reduced heart rate by 32.3%, changes that were significantly attenuated by MK-467 after their occurrence.
• The use of step infusions helped in narrowing down the therapeutic range for the MED/MK infusion dose ratio during isoflurane anaesthesia in dogs.

The haemodynamic interactions of a step infusion with medetomidine (MED) and the peripherally acting alpha-2 antagonist MK-467 (MK) were compared with MED infused alone in isoflurane-anaesthetised dogs. Eight purposely-bred Beagles were used in a randomised crossover study. Anaesthesia was induced with propofol intravenously (IV) and maintained with isoflurane in oxygen. Dogs received 1.25 µg/kg MED as a 1 min loading dose IV, along with a step-down MED infusion at rates of 8.0 µg/kg/h (step 1: 0–20 min), 5.5 µg/kg/h (step 2: 20–40 min) and 4.0 µg/kg/h (step 3: 40–95 min). Five minutes after starting the MED infusion, the dogs received MK-467 in a step-up infusion at rates of 100 µg/kg/h (step 1: 5–35 min), 200 µg/kg/h (step 2: 35–65 min) and 500 µg/kg/h (step 3: 65–95 min). Heart rate (HR), systolic (SAP) and mean arterial (MAP) blood pressures and arteriovenous oxygen content differences (a-vO2 diff) were calculated. Plasma drug concentrations were analysed. Repeated-measures general linear mixed models with Bonferroni correction were used for statistical analyses.MED infusion alone increased SAP maximally by 24.9%, MAP by 34.7% and a-vO2 diff by 222.5%, and reduced HR by 32.3%, but these changes were significantly attenuated by MK-467. Most MED effects returned to baseline during step 2 of MK-467 infusion and step 3 of MED infusion (MED/MK-467 ratio 1:18 to 1:50). Plasma concentrations of MED tended to be lower with the addition of MK-467. The use of step infusions helped to narrow down the therapeutic range for the MED/MK-467 infusion dose ratio during isoflurane anaesthesia in dogs.