Nonlinear additivity of nitrous oxide and isoflurane potencies in rats.
OBJECTIVE
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 s.c. 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 - 159 +/- 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).


CONCLUSIONS
Nonlinear additivity was demonstrated with direct MAC measurement for both isoflurane and N2O in rats. This suggests an agonist-antagonist relationship.
Russell
G B
GB
Department of Anesthesia, Milton S. Hershey Medical Center, Pennsylvania State University College of Medicine, Hershey 17033, USA.
Graybeal
J M
JM
D018685:Anesthetics, Inhalation / Q000008:administration & dosage*; D000818:Animals; D004357:Drug Synergism; D007530:Isoflurane / Q000008:administration & dosage* / Q000493:pharmacokinetics; D008297:Male; D009609:Nitrous Oxide / Q000008:administration & dosage* / Q000493:pharmacokinetics; D011650:Pulmonary Alveoli / Q000378:metabolism; D051381:Rats
D018685:Anesthetics, Inhalation; D007530:Isoflurane; D009609:Nitrous Oxide