Abstract
To evaluate the effects of increasing plasma ketamine concentration on isoflurane minimum alveolar concentration (MAC) in rabbits, six New Zealand white rabbits weighing 4.21 ± 0.35 kg were anesthetized with isoflurane in oxygen. Ketamine was given intravenously to target pseudo-steady-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. The 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, and 0.71 ± 0.06 for the six targeted plasma ketamine concentrations. MAC was significantly lower than baseline for the target concentration of 1 μg mL(-1) and above. Heart rate was significantly reduced from baseline at 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 were observed in some rabbits, requiring active cooling to maintain normothermia. Recoveries were unremarkable. MAC at plasma ketamine concentration C was predicted to be 1.85 - 1.25/2.96 . Increasing ketamine concentrations reduced isoflurane MAC in healthy female New Zealand White rabbits. Plasma ketamine concentrations between 1 and 4 μg mL(-1) may elicit benefit with minimal adverse effects.