Nonlinear additivity of nitrous oxide and isoflurane potencies in rats

Purpose: To test the hypothesis that the MAC values of nitrous oxide (N2O) and isoflurane were not linearly additive, as theorized by the postulated mode of action based on lipid solubility, in a rat model. Methods: Eight Long Evans rats were randomly assigned to order of measurement of MAC for isoflurane and N2O alone and in combination using standard 45 sec supramaximal electrical stimulation (50 volts x 10 msec duration pulses at 50.sec(-1) applied for 45 sec sc to the lower abdominal groin area). The MAC of N2O was measured at hyperbaric compression to 2.25 atmospheres absolute, 1710 mmHg. Results: The MAC values found were: isoflurane -0.98 +/- 0.12 and N2O - 59 +/- 12 volume (vol)%, or 1.59 +/- 0.12 atmospheres absolute (ATA) (All values are mean +/- standard deviation), The linear additivity theory suggests % MAC agent A + % MAC agent B = 1.0, However, % MAC isoflurane + % MAC N2O = 1.37 +/- 0.15 (P < .001). Conclusion: Nonlinear additivity was demonstrated with direct MAC measurement for both isoflurane and N2O in rats, This suggests an agonist-antagonist relationship.