Although most inhaled anesthetics are eliminated unchanged through the lungs, a small portion is metabolized in the body, primarily in the liver. This metabolism occurs through phase I and phase II reactions. Phase I reactions include hydrolysis and oxidation, which are catalyzed by enzymes like the cytochrome P450 family, particularly CYP2E1. Phase II reactions involve conjugating the metabolites with substances like glucuronyl or methyl groups, making them more water-soluble and easier to excrete. Despite these metabolic processes, the extent of metabolism for modern inhaled anesthetics is minimal.
Halothane, an older anesthetic, undergoes the highest degree of metabolism, with 20-50% of the drug being processed by the liver. This extensive metabolism is associated with halothane’s potential for causing liver damage, which is why it is no longer widely used. Sevoflurane undergoes about 2% metabolism, while isoflurane and desflurane are metabolized at even lower rates, about 0.2% and 0.02%, respectively. Methoxyflurane, which is no longer in use, was an exception among inhaled anesthetics due to its significant metabolism. The minimal metabolism of modern agents helps reduce the risk of toxicity and organ damage, making them safer for use.
| Agent | Extent metabolized | Why it matters |
|---|---|---|
| Halothane | 20–50% | Highest of the inhaled agents; associated with liver damage, which is why it is no longer widely used |
| Sevoflurane | About 2% | Produces inorganic fluoride ions; the balance of the drug is exhaled unchanged |
| Isoflurane | About 0.2% | Minimal metabolic transformation, reducing the risk of toxicity and organ damage |
| Desflurane | About 0.02% | The least metabolized of the modern agents |
| Methoxyflurane | Significant | An exception among the inhaled agents; no longer in use |
