Abstract
The analgesic effect of 50% nitrous oxide and oxygen on thermal pain sensations was evaluated in a placebo-controlled, double-blind crossover design. In a session immediately before oral surgery, 20 patients used a seven-point verbal scale to rate the intensity of pain sensations evoked by three-second thermal stimuli delivered to 14 sites on the volar forearm at 20-second intervals by a 1-cm-diameter contact thermode. Subjects rated 36 stimuli while breathing room air and then two additional sets of 36 stimuli while inhaling 50% nitrous oxide and oxygen during one set and oxygen placebo during the other. Each of these two stimulus sets was preceded by a two-minute induction of the agent, and the sets were separated by a three-minute washout period. Order of administration was randomized and counterbalanced. Stimulus temperatures were adjusted continuously by an interactive computer program so that response could be maintained at predetermined levels. This method resulted in a continuous measure of analgesia in units of stimulus intensity. Results showed that, in comparison with placebo, nitrous oxide significantly increased the stimulus temperatures (mean = 0.42°C) required to make the same response [F (11,209) = 6.76, p <0.0001], indicating analgesia. This increase was one-third to one-half that observed with clinical doses of intravenous fentanyl. Analgesic effects were apparent at three min and waned 10 min after termination of nitrous-oxide inhalation. These times closely correlated with previous measures of alveolar concentration, further supporting the fast but modest analgesic action of nitrous oxide.
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