Isoflurane

Lore & Background

Isoflurane is indicated for induction and maintenance of general anesthesia, always administered with air or pure oxygen, often with nitrous oxide. Although its physical properties imply anesthesia can be induced more rapidly than with halothane, its pungency can irritate the respiratory system, so it is mostly used as a maintenance agent after induction with an intravenous agent such as thiopentone or propofol. The exact mechanism of action has not been clearly delineated, but isoflurane likely binds to GABA, glutamate, and glycine receptors, acting as a positive allosteric modulator of the GABAA receptor, potentiating glycine receptor activity, and inhibiting NMDA glutamate receptor subtypes and activated potassium channels. It also inhibits plasma membrane calcium ATPases and binds to the D subunit of ATP synthase and NADH dehydrogenase.

Reader's Guide

Isoflurane's significance lies in its role as a widely used inhalational anesthetic, particularly for maintenance of general anesthesia, replacing flammable ethers alongside enflurane and halothane. However, its use is tempered by side effects including respiratory depression, low blood pressure, and irregular heartbeat, as well as serious risks such as malignant hyperthermia and high blood potassium. Its legacy includes ongoing research into potential links to Alzheimer's disease and concerns about neurodegeneration in young children when combined with nitrous oxide and benzodiazepines, though whether these concerns occur in humans is unclear.

Did You Know?

• Isoflurane has a minimum alveolar concentration (MAC) of 1.15 vol %.
• Its blood/gas partition coefficient is 1.4, and its oil/gas partition coefficient is 98.
• Isoflurane is administered as a racemic mixture of (R)- and (S)-optical isomers.
• The average lifetime of isoflurane in the atmosphere is 3.2 years.