Mixtures of inhalation and i.v. anaesthetics at high pressure. A test of the multi-site hypothesis of general anaesthesia.

We have tested the hypothesis that anaesthetics having different pressure reversal characteristics act at different molecular sites with finite capacities and, therefore, do not necessarily have additive potencies when used in mixtures of varying composition. The additivity of the anaesthetic potencies has been tested at normal pressures and at pressures up to 100 ATA for eight combinations of the following mixtures: Althesin plus nitrous oxide; methohexitone plus nitrous oxide; thiopentone plus nitrous oxide; thiopentone plus propanidid. The anaesthetic potencies of the first two mixtures were not additive at increased pressures, whereas those of the latter two mixtures were additive. These data support the multi-site hypothesis of general anaesthesia.