Desflurane animal and human pharmacology: aspects of kinetics, safety, and MAC

Abstract

Substitution of fluorine for the single chlorine atom in isoflurane produces the new anesthetic, desflurane. This seemingly small change produces several pharmacologic changes. The potency of desflurane (MAC equals 6.0% in middle-aged patients) is one-fifth that of isoflurane (1.15%), with MAC for each agent decreased by aging, hypothermia, or the addition of depressants such as midazolam, fentanyl, or nitrous oxide. Some properties are similar: desflurane and isoflurane both depress respiration and neuromuscular contractility, and higher concentrations (e.g., 6%-8% desflurane) of both agents have a pungency that can provoke breath holding, laryngospasm, and salivation, particularly in infants and children. Of great importance, the substitution of fluorine for chlorine markedly decreases blood (desflurane blood-gas partition coefficient 0.42) and tissue solubility (e.g., brain-blood partition coefficient 1.3) relative to isoflurane (values 1.4 and 1.6, respectively). As a result, desflurane alveolar concentrations may be adjusted more rapidly and precisely; desflurane enters and leaves the lungs and tissues more rapidly; and recovery is quicker both for the short (first 10-20 min) and long (0.5-1.5 h) term. This greater precision of control and more rapid recovery are consistent with trends for new drug development in anesthesiology.