Relationship of concentrations of halothane and enflurane to their metabolism and elimination in man.

Abstract

In order to assess the impact of anesthetic metabolism on elimination of halothane and enflurane, three groups of healthy, lean young men were given enflurane and halothane concomitantly for two hours. Six awake volunteers (Group I) breathed 0.21 per cent enflurane and 0.11 per cent halothane in air. Four surgical patients (Group II) breathed the same anesthetic concentrations with 70 per cent N2O. Five more surgical patients (Group III) breathed these volatile agents in concentrations that were four times greater, also in 70 per cent N2O. All surgical patients received anesthetic adjuvant drugs (morphine, diazepam, thiopental, and pancuronium) as clinically indicated. End-tidal and inspired anesthetic concentrations were measured during anesthetic administration and for three to five days thereafter. Anesthetic uptake, elimination, and metabolism were calculated. Data from Groups I and II were comparable. Forty-five per cent of the halothane and 90 per cent of the enflurane taken up were recovered. The smaller recovery of halothane was associated with a more rapid reduction in the end-tidal concentration of halothane than enflurane at the end of anesthesia. Group III differed from Groups I and II in that significantly more halothane (59 per cent) was recovered, while 90 per cent of enflurane was again recovered. In addition, for the first 30 to 205 min of elimination, the halothane end-tidal concentration decreased more slowly than did the enflurane end-tidal concentration. We conclude that a greater fraction of the halothane taken up at subanesthetizing, as opposed to anesthetizing, concentrations is metabolized. This difference explains why elimination of halothane at subanesthetizing concentrations is more rapid than is elimination of enflurane, a less soluble but also less easily metabolized agent. Indeed, the absolute or total amount of drug metabolized was greater in the higher-concentration study (Group III), only the relative percentage of drug taken up that was not recovered (a measure of the percentage metabolized) was smaller. Furthermore, in this study, nitrous oxide and the anesthetic adjuvants morphine, diazepam, thiopental, and pancuronium had no significant effect on the extent of halothane or enflurane metabolism.