Comparison of the Effects of Subanaesthetic Concentrations of Isoflurane or Nitrous Oxide in Volunteers

Abstract

A cross-over trial was performed in 12 volunteers to compare the relative potency of 25% nitrous oxide and 0.4% isoflurane when breathed for a period of 20 min. Oxygen was used as a control. The effects were observed for 35 min after drug administration. Choice reaction time, ability to tap two areas on a board and ability to perform mathematical problems were significantly impaired when inhaling nitrous oxide, the maximum effect being obtained within 5 min. With isoflurane, the effects were significantly greater than with nitrous oxide. The effect obtained after 15 min inhalation was greater than that at 5 min. Tests returned promptly to the base line after the discontinuation of the test agent. Subjective assessments were made using a series of eight visual analogue scales. Results of the scales represented by physical and mental sedation indicated that 0.4% isoflurane was more potent than 25% nitrous oxide. Significant effects were detected up to 15 min after the inhalation of the agent was stopped. Subanaesthetic concentrations of isoflurane warrant further study in patients undergoing dental treatment in which a rapid recovery from sedation is important.

The subjective, behavioral and cognitive effects of subanesthetic concentrations of isoflurane and nitrous oxide in healthy volunteers

“…The fact that isoflurane had a detectable odor and that it was disliked is not surprising. Others have described the odor of isoflurane as pungent and medicinal in quality (Marshall and Longnecker 1990), and unpleasant (e.g., McMenemin and Parbrook 1988;Rodrigo and Rosenquist 1988). The odor also disrupted the double blind nature of the study.…”

“…We used a simulation model (Gasman 1990) to estimate that by using higher concentrations of isoflurane (0.3% and 0.6%), isoflurane levels would be at 0.2 and 0.4% by our main testing time (15 min intra-inhalation), with little change occurring throughout the rest of the session. Other investigators have also used slightly higher isoflurane concentrations when comparing equi-MAC concentrations of N20 and isoflurane to control for the slower equilibration time of the latter agent (McMenemin and Parbrook 1988;Rodrigo and Rosenquist 1988).…”

“…In volunteers, 0.4% isoflurane produced impairment in choice reaction time, ability to tap two areas on a board, and ability to do math problems -impairment was greater 15 min intra-inhalation than 5 min intra-inhalation (McMenemin and Parbrook 1988). However, unlike subjective effects which tended to linger after isoflurane inhalation had ceased, psychomotor performance returned to baseline immediately upon cessation of isoflurane inhalation.…”

“…Its subjective effects have been examined in one laboratory study, and only anecdotally assessed in clinical studies. In the laboratory study (McMenemin and Parbrook 1988), which involved healthy volunteers who worked in an anesthesiology department, visual analog scale ratings of "drowsy," "mentally slow," "clumsy," "lethargic," "calm," and "relaxed" increased during inhalation of 0.4% isoflurane. Some of these subjective effects, including ratings of drowsy and lethargic, were still apparent 15 min after discontinuation of the test agent.…”

MAC-Awake of Isoflurane, Enflurane and Halothane Evaluated by Slow and Fast Alveolar Washout

“…Our data thus demonstrate clinically important differences in hypnotic potencies of volatile anaesthetics, with isoflurane and enflurane being approximately twice as potent as halothane, ether, methoxyflurane or fiuroxene [1]. It was shown also that subanaesthetic doses of isoflurane produced more mental and physical sedation than equianaesthetic doses of nitrous oxide [10]. These data therefore permit selection of volatile anaesthetics for the desired degree of sedation during anaesthesia or in the intensive care unit [11].…”