Pharmacokinetics of sevoflurane uptake into the brain

• Published in: Anaesthesia 2004-12, Vol.59 (12), p.1201-1206
• Main Authors: Turner, M. J., McCulloch, T. J., Kennedy, R. R., Baker, A. B.
• Format: Article
• Language: English
• Subjects: Anesthesia; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Anesthetics, Inhalation - blood; Anesthetics, Inhalation - pharmacokinetics; Biological and medical sciences; Blood-Brain Barrier; Brain - metabolism; brain. Anaesthetics; Computer Simulation; Humans; inhalational; Jugular Veins; Medical sciences; Methyl Ethers - blood; Methyl Ethers - pharmacokinetics; Models, Biological; Partial Pressure; Pharmacokinetics; sevoflurane; Tissue Distribution
• ISSN: 0003-2409; 1365-2044
• DOI: 10.1111/j.1365-2044.2004.03966.x

Summary Two recent studies have examined the pharmacokinetics of sevoflurane in adults. Lu et al.(Pharmacokinetics of sevoflurane uptake into the brain and body, Anaesthesia 2003; 58: 951–6) observed that jugular bulb sevoflurane concentration initially rose unexpectedly rapidly and then approached arterial concentrations unexpectedly slowly, suggesting that a blood–brain diffusion barrier exists. They also observed a large alveolar‐arterial sevoflurane gradient, suggesting that an alveolar–arterial diffusion barrier exists. Nakamura et al. (Predicted sevoflurane partial pressure in the brain with an uptake and distribution model: Comparison with the measured value in internal jugular vein blood. Journal of Clinical Monitoring and Computing 1999; 15: 299–305) found no diffusion barriers. We used a computer model to analyse both data sets and show that the observations of Lu et al. can be explained by contamination of jugular samples with extracerebral blood. It is possible that the alveolar‐arterial gradients observed by Lu et al. are due to discrepancies in conversions between blood concentrations and gas partial pressures. Our study suggests that there is no blood–brain diffusion barrier for sevoflurane and that the data of Lu et al. must be interpreted with caution.