New inhalational agents--desflurane and sevoflurane.

Many of the drugs newly introduced into anaesthetic practice have in common a kinetic profile that permits a more rapid and precise adjustment of effect, including a more rapid recovery of normal function. Sevoflurane and desflurane fit this mold. These new inhaled anaesthetics differ kinetically from isoflurane and halothane because of their lower solubility in blood (Table), a feature produced by haiogenation solely with fluorine [CHF 2O-CFH-CF3 (desflurane); CFH2-O-(CF3)2 (sevoflurane)]. Desflurane also has lower tissue/blood partition coefficients than any of the other three anaesthetics. Desflurane differs from isoflurane (CHF2-O-CC1HCF3) only by the substitution of a fluorine for a chlorine atom. The substitution of fluorine for chlorine changes many properties. It decreases potency (e.g., MAC for sevoflurane in middle-aged patients is 2% and for desflurane is 6%; compare the latter value with that of 1.15% for isoflurane) and increases vapour pressure at room temperature (670 mmHg for desflurane and 170 mmHg for sevoflurane). The MAC-awake (the concentration permitting voluntary response to command in 50% of patients) is about a third of MAC for both agents. 5,6 This finding is important because MAC-awake is thought to indicate the concentration providing amnesia in most patients. That is, it suggests that desflurane and sevoflurane are potent amnestics. The strength of the carbon-fluorine bond* increases stability, a fortunate effect because alkali (e.g., soda lime or Baralyme) degrades sevoflurane, especially at the increased temperatures found in the carbon dioxide absorber needed for closed circuit anaesthesia. Were the stability less, sevoflurane might not be clinically useful. In contrast, desflurane resists degradation by alkali and does so more than its chlorinated analog, isoflurane. The lower solubility of desflurane and sevoflurane indicates a more rapid rate of rise of the alveolar concentration towards the concentration inspired. Results from several studies confirm this prediction. ?,8 In the case of sevoflurane, the rapidity of change correctly implies a rapidity of induction of anaesthesia. Sevoflurane has replaced halothane for induction of anaesthesia in children in at least one hospital in Japan, a country where sevoflurane has been released for clinical use. In contrast, the pungency of desflurane results in respiratory tract irritation and coughing, breathholding and laryngospasm, particularly at concentrations of 7% or greater. These responses limit desflurane's usefulness as an induction agent, and desflurane is not recommended for this purpose, especially in children. Once induction is complete, the issue of pungency appears to be minor or non-existent as a factor affecting clinical practice. During maintenance, the concentration of desflurane or sevoflurane can be rapidly adjusted to meet changing clinical needs. Furthermore, the difference between the concentration inspired and that in the alveoli is relatively small. That is, the alveolar concentration can be known with fair precision by knowing the concentration inspired. In turn, given a modest inflow rate (2 L . min -j or greater), the difference between the concentration delivered from the vaporizer and that in inspired gas becomes small. Thus, the alveolar concentration and the level of anaesthesia may be controlled and known if one uses an accurately calibrated vaporizer and a modest inflow rate. The same is not true for more soluble anaesthetics where the difference between the concentration delivered and that in the alveoli may be considerable. As would be predicted from their low solubilities, recovery from anaesthesia during the first 10--20 min after anaesthesia is faster with either agent than with isoflurane. T M In addition, the more rapid return towards normal from desflurane anaesthesia may be documented for at least an hour and a: half after the termination of anaesthetic administration. ~0,]2 Whether this translates into a more rapid release from the recovery room and a more rapid return to normality at home or on the job remains to be adequately tested, but the results of at least one study suggest this possibility for desflurane, z2 To make use of the potential for an earlier release from the recovery room may require the development of new guidelines for the dismissal of patients. Many of the remaining pharmacological characteristics of desflurane and sevoflurane resemble those familiar to the practitioner who administers agents such as isoflurane or halothane. All depress respiration, raising PaCO2 and decreasing the ventilatory response to imposed increases