Metabolism and elimination of inhaled anaesthetics

Microsomal enzymes responsible for metabolism are mainly located in the liver and kidneys. The rates of metabolism in the human body are approximately 10 to 20 per cent for halothane, 2.5 per cent for enflurane, about 0.2 per cent for isoflurane, and zero per cent for nitrous oxide.

Approximately 3% of the absorbed dose of sevoflurane is metabolised.  It undergoes hepatic metabolism by cytochrome P450 (isoform 2E1).  Hexafluoroisopropanol and inorganic fluoride (know to cause renal toxicity) are produced.

When sevoflurane is administered in a circle system using soda lime or baralyme, a number of compounds are produced.  Compounds A, B, C, D and E have all been identified, although only compounds A and B (the latter being less toxic) are present in sufficient quantities to make analysis feasible.  The lethal concentration in 50% of rats is 300-400 ppm after 3 hours' exposure.  Extrapolation of these and other animal studies suggest a human nephrotoxic threshold of 150-200 ppm.  Recent work suggests that even with flow rates of 0.25 L/min for 5 hours, the level of compound A peaks at less than 20 ppm and is not associated with abnormal tests of renal function.

0.02% of an administered dose of desflurane is metabolised, predominantly to trifluoroacetic acid.

The amount of anaesthetic removed from the body by metabolism is small compared with the amount exhaled. Induction and recovery from anaesthesia with volatile anaesthetics differ somewhat from each other. On induction, all tissue partial pressures are zero. During recovery, different tissues in the body have a different partial pressure of the inhaled anaesthetic. Therefore, recovery is not as controllable as induction of anaesthesia. In addition, increasing minute ventilation and concentration of the inspired anaesthetic mixture can significantly accelerate induction. Increasing minute ventilation with high inspiratory oxygen concentration will increase the gradient of the inhaled anaesthetic between pulmonary venous blood and the alveolar space, and therefore increase the elimination of the gas.