Interaction of Isoflurane and Nitrous Oxide Combinations Similar for Median Electroencephalographic Frequency and Clinical Anesthesia

Background The volatile anesthetic sparing effect of nitrous oxide in clinical studies is less than might be expected from the additivity of minimum alveolar concentration values. Other studies identify nonadditive interactions between isoflurane and nitrous oxide. The aim of this study was to quantify the interaction of isoflurane and nitrous oxide at a constant median electroencephalographic frequency. Methods Twenty-five patients were studied during laparotomies. Nitrous oxide was randomly administered in concentrations of 0, 20, 40, 60, and 75 vol%, to ten patients for each nitrous oxide concentration. Isoflurane vaporizer settings were chosen so that the median electroencephalographic frequency was held between 2 and 3 Hz. The relationship between nitrous oxide concentrations and required isoflurane concentrations was examined with the method of isoboles. Results Nitrous oxide linearly decreased the isoflurane requirement. Addition of every 10 vol% of nitrous oxide decreases the isoflurane requirement by approximately 0.04 vol%. The total anesthetic requirement of isoflurane and nitrous oxide, expressed in terms of previously reported minimum alveolar concentration values, increased significantly with increasing nitrous oxide concentrations. Conclusions The interaction of isoflurane and nitrous oxide in the dose range 0-75 vol% on median electroencephalographic frequency is compatible with additivity. The potency of nitrous oxide as a substitute for isoflurane is less than on a minimum alveolar concentration basis. Maintaining median electroencephalographic frequency more appropriately reflects the clinical usage of isoflurane and nitrous oxide than does maintaining minimum alveolar concentration.