Progressive changes in electroencephalographic responses to nitrous oxide in humans: a possible acute drug tolerance

The possibility of acute tolerance to nitrous oxide was examined during halothane anesthesia in humans. Nitrous oxide was added to the inspired gas twice. The first admixture induced three successive stages of electroencephalogram (EEG): delta-waves lasting for 13 +/- 12 min, theta-waves lasting for 41 +/- 21 min, and, finally, spindle-type waves. The spindle-type EEG was similar to that of halothane anesthesia in configuration, but smaller in amplitude and faster in frequency than that seen during halothane anesthesia. The second admixture, given after a 20-30-min interval, induced a continuous delta-wave EEG in one patient, theta-waves followed by spindle EEG in eight patients, and spindle-type EEG in four patients. The successive changes of electroencephalographic response during the first admixture indicate that an alteration of central nervous system function occurred. The altered state was maintained in the absence of nitrous oxide: responses to a second admixture were characteristic of the later, altered, stages of responses seen after the first admixture. These findings support the view of acute tolerance to nitrous oxide.