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.
A composite statistical analysis was made of the results from four trials comprising patients undergoing upper abdominal operations. It revealed a marked correlation between the neuroticism score as measured by a personality inventory before operation and the percentage vital capacity impairment found after operation. Neuroticism correlated also with pain as measured by a visual analogue scale. The vital capacity impairment and subjective pain readings were interrelated and both neuroticism and vital capacity impairment were related to the chest complication rate. Personality assessment before operation can identify one group of patients who will have marked pain and limitation of vital capacity after operation.
Nitrous oxide has had a wide use as an analgesic in midwifery and in dental surgery, but its use does not appear to have been investigated for the relief of post-operative wound pain.We describe here a study designed to compare the relative potency of nitrous oxide and morphine for relief of pain in patients during the first 48 hours after upper abdominal operations. Post-operative pain in such patients restricts breathing to a marked degree, and the relief by analgesics of this restriction can be assessed by simple tests of vital capacity in the manner described by Overholt (1930), Bromage (1955), and Masson (1962. Previous work on volunteers (Chapman et al., 1943 ;Sonnenschein et al., 1948 ;Delisle Burns et al., 1960;Dundee and Moore, 1960;Parkhouse et al., 1960;Dundee et al., 1962) suggested that 25% nitrous oxide in oxygen was the most suitable concentration for this study.
Material and MethodsThe investigation was limited to patients under the age of 60 who had operation wounds in or extending to the upper abdomen. Prior to operation the patients were seen, the nature of the trial was explained, and their co-operation obtained; vital capacity and peak expiratory flow readings were then measured and the nitrous oxide and oxygen breathing apparatus was demonstrated.If vital capacity is measured before operation and again after operation, when the patient is fully recovered from the anaesthetic, its diminution gives some measure of the impairment of respiratory movement. This can be taken as some measure of the degree of pain. If this pain is then relieved by an analgesic the vital capacity increases in proportion to the efficacy of the drug. A perfect analgesic will restore the vital capacity to virtually the pre-operative value, whereas a drug having no effect will make no difference to the vital capacity. We therefore used changes in vital capacity, and, to a less extent, those in peak expiratory flow rate, as a way of assessing the analgesic effects of nitrous oxide and morphine.Vital Capacity.-This was measured by the Wright respirometer used with a mouth-piece and Ruben valve, and with a nose-clip applied. After practice readings the mean of three readings was noted. Although the Wright respirometer is less accurate than bulkier apparatus for vital capacity measurement, it was thought to give satisfactory comparative readings since the same respirometer was used in every case.Peak Expiratory Flow Rate.-The Wright peak flow meter was used and the mean of three readings taken after practice " puffs." 25% Nitrous Oxide in Oxygen Mixture.-The mixture was delivered to the patient from a specially calibrated Walton 5 machine using a reservoir bag and a non-rebreathing circuit with a Ruben valve. The " pressure " control was adjusted so that the reservoir bag did not collapse during inspiration while
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