Canadian Journal of Anesthesia, Vol 45, 466-470, Copyright © 1998 by Canadian Anesthesiologists' Society

ARTICLES

Nonlinear additivity of nitrous oxide and isoflurane potencies in rats

GB Russell and JM Graybeal
Department of Anesthesia, Milton S. Hershey Medical Center, Pennsylvania State University College of Medicine, Hershey 17033, USA.

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 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). CONCLUSION: Nonlinear additivity was demonstrated with direct MAC measurement for both isoflurane and N2O in rats. This suggests an agonist-antagonist relationship.

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