Increasing plasma ketamine concentrations decrease minimum alveolar concentrations of isoflurane in rabbits

Linda Susan Barter^*Bruno Pypendop

• University of California, Davis, Davis, United States

To evaluate the effects of increasing plasma ketamine concentration on isoflurane minimum alveolar concentration (MAC) in rabbits 6 New Zealand white rabbits weighing 4.21 ± 0.35 kg were anesthetized with isoflurane in oxygen. Ketamine was given intravenously to target pseudosteady-state plasma concentrations of 0.5, 1, 2, 4, 8 and 12 µg mL -1 . MAC, heart rate, arterial blood pressure, body temperature, end-tidal carbon dioxide concentration and plasma ketamine concentration were measured at each targeted ketamine concentration. A pharmacodynamic model was fitted to the plasma ketamine concentration-MAC data. Measured plasma ketamine concentrations were 0.53 ± 0.14, 1.25 ± 0.2, 2.64 ± 0.44, 5.11 ± 1.18, 8.96 ± 2.03, and 18.07 ± 4.2 µg mL -1 and isoflurane MAC values (% atm) were 1.66 ± 0.04, 1.39 ± 0.17, 1.16 ± 0.13, 1.02 ±0.15, 0.86 ± 0.17, 0.71 ± 0.06 for the 6 targeted plasma ketamine concentrations respectively. MAC was significantly lower than baseline for the target concentration of 1 µg mL -1 and higher. Heart rate was significantly lower than baseline values for plasma target ketamine concentrations of 2 µg mL -1 and higher. At target ketamine concentrations of 8 and 12 mcg mL -1 increased muscle tone and spontaneous movement occurred in some rabbits requiring active cooling to maintain normothermia. Recoveries were unremarkable. MAC at plasma ketamine concentration C was predicted to be 1.85 -!.#$×& #.'()& . Increasing ketamine concentrations reduced isoflurane MAC in healthy female New Zealand White rabbits. Plasma ketamine concentrations between 1 to 4 µg mL -1 may elicit benefit with minimal adverse effects.