Some aspects of the clinical pharmacology of nitrous oxide.

NIvaotrs OXIDE has been employed in anaesthesia since the beginning of the art itself. 1 This anaesthetic agent, therefore, must be considered to have stood the test of time and there can surely be few anaesthetists who would find themselves questioning its safety. As it is employed in modern anaesthetic practice, nitrous oxide is generally regarded as an adjuvant to balanced anaesthesia with few disadvantages other than low potency. It is well known, of course, that prolonged administration of this gas, for 24 hours or more, may be followed by leueopaenia 2 and that this effect is a function of the ability of nitrous oxide to influence cell division. This property of the agent may, perhaps, have greater significance for operating room personnel undergoing daily exposure than for patients who are anaesthetised for surgical procedures. 3 Nitrous oxide is capable of supporting combustion although it is not inflammable. 4 This property of the agent is probably of limited clinical significance. We are aware that the solubility of nitrous oxide in relation to that of nitrogen is as 30:1. 5 Thus, air containing body cavities such as dosed loops of bowel 6 and cerebral ventricles during air encephalography r may undergo distention when nitrous oxide is employed in the inspired anaesthetic mixture, because the ready diffusion of the gas into these nitrogen-containing spaces is faster than the egress of the nitrogen. At this point it is worth remarking how very frequently nitrous oxide is employed in modern anaesthetic practice. Since the pendulum has swung from the use of explosive agents (eschewing in particular cyclopropane and diethyl ether) nitrous oxide has been employed as an adjuvant for the volatile hydrocarbons, intravenous narcotics, the so-called dissociative anaesthetics and, accompanied by neuromuscular blockade and modest hyperventilation, as a principal anaesthetic agent in one form of balanced anaesthesia. Indeed, it is reasonable to consider this agent as the leitmotiv against which the remainder of the symphony of much of modern general anaesthesia is currently played. It is interesting, therefore, to note that until recently comparatively few studies of the pharmacology of this agent had been conducted. 8,5 Its very marked record of apparent safety would appear to have protected it from searching clinical investigation or laboratory study until recent years.