G Lockwood1. 1. Centre for Perioperative Medicine and Critical Care Research, Hammersmith Hospital, Ducane Road, London W12 0HS, UK. g.lockwood@imperial.ac.uk
Abstract
BACKGROUND: Context-sensitive times to 50%, 80%, and 90% elimination from the brain have been calculated for volatile anaesthetics. This does not represent complete recovery because there are important residual effects even at 90% elimination, and the effect of anaesthetic metabolism on the rate of elimination has not been considered. METHODS: A physiologically based model of anaesthetic uptake and distribution was elaborated to include anaesthetic metabolism and fluoride kinetics. It was validated by comparing its predictions with real data, then experiments were undertaken to calculate the partial pressure of anaesthetic in the brain after the administration of 1 MAC of halothane, enflurane, isoflurane, sevoflurane or desflurane, or 50% of inspired nitrous oxide or xenon, for up to 6 h. RESULTS: The model generated data that were compatible with many published measurements of anaesthetic kinetics and fluoride production. Metabolism had a negligible effect on kinetics. After 4 h of anaesthesia, the model predicted body content to be 28 g nitrous oxide, 26 g desflurane, 14 g sevoflurane, or 15 g isoflurane, and 99.9% brain elimination times were then 9 h for nitrous oxide, 33 h for desflurane, 52 h for sevoflurane, and 71 h for isoflurane. At this stage of elimination, the whole body still retained between 4% and 13% of the absorbed dose. Differences between sevoflurane and desflurane were obvious only during the final stages of elimination (>99% from the vessel-rich group). CONCLUSIONS: Large amounts of anaesthetics are absorbed during anaesthesia and significant amounts remain in the body for days after apparent recovery.
BACKGROUND: Context-sensitive times to 50%, 80%, and 90% elimination from the brain have been calculated for volatile anaesthetics. This does not represent complete recovery because there are important residual effects even at 90% elimination, and the effect of anaesthetic metabolism on the rate of elimination has not been considered. METHODS: A physiologically based model of anaesthetic uptake and distribution was elaborated to include anaesthetic metabolism and fluoride kinetics. It was validated by comparing its predictions with real data, then experiments were undertaken to calculate the partial pressure of anaesthetic in the brain after the administration of 1 MAC of halothane, enflurane, isoflurane, sevoflurane or desflurane, or 50% of inspired nitrous oxide or xenon, for up to 6 h. RESULTS: The model generated data that were compatible with many published measurements of anaesthetic kinetics and fluoride production. Metabolism had a negligible effect on kinetics. After 4 h of anaesthesia, the model predicted body content to be 28 g nitrous oxide, 26 g desflurane, 14 g sevoflurane, or 15 g isoflurane, and 99.9% brain elimination times were then 9 h for nitrous oxide, 33 h for desflurane, 52 h for sevoflurane, and 71 h for isoflurane. At this stage of elimination, the whole body still retained between 4% and 13% of the absorbed dose. Differences between sevoflurane and desflurane were obvious only during the final stages of elimination (>99% from the vessel-rich group). CONCLUSIONS: Large amounts of anaesthetics are absorbed during anaesthesia and significant amounts remain in the body for days after apparent recovery.