Anesthesiology
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Randomized Controlled Trial Clinical Trial
Clinical sevoflurane metabolism and disposition. II. The role of cytochrome P450 2E1 in fluoride and hexafluoroisopropanol formation.
Sevoflurane is metabolized to free fluoride and hexafluoroisopropanol (HFIP). Cytochrome P450 2E1 is the major isoform responsible for sevoflurane metabolism by human liver microsomes in vitro. This investigation tested the hypothesis that P450 2E1 is predominantly responsible for sevoflurane metabolism in vivo. Disulfiram, which is converted in vivo to a selective inhibitor of P450 2E1, was used as a metabolic probe for P450 2E1. ⋯ Disulfiram, an effective P450 2E1 inhibitor, substantially decreased fluoride ion and HFIP production during and after sevoflurane anesthesia. These results suggest that P450 2E1 is a predominant P450 isoform responsible for human sevoflurane metabolism in vivo.
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Randomized Controlled Trial Clinical Trial
Pharmacokinetic model selection for target controlled infusions of propofol. Assessment of three parameter sets.
Computer-assisted target controlled infusions (TCI) result in prediction errors that are influenced by pharmacokinetic variability among and within patients. It is uncertain whether the selection of a propofol pharmacokinetic parameter set significantly influences drug concentrations and clinical acceptability. ⋯ Although it may be preferable to administer propofol TCI by using a locally derived parameter set, it is acceptable to use a model from elsewhere. The Marsh and Tackley models produced equally good performance and are appropriate for propofol TCI within the range of 3-6 micrograms/ml. The Dyck model was less accurate at maintaining anesthetic concentrations, possibly because it was derived from low concentrations. Concentrations in blood, the most sensitive indicators of performance, demonstrated differences among the parameter sets. Clinically, TCI worked well, and by clinical criteria, the choice of pharmacokinetic model did not appear to make a difference.
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Randomized Controlled Trial Clinical Trial
Oral clonidine prolongs lidocaine spinal anesthesia in human volunteers.
Premedication with oral clonidine may improve the quality and duration of lidocaine spinal anesthesia, but this effect has not been examined in a quantitative fashion. ⋯ Premedication with oral clonidine prolonged sensory and motor block from lidocaine spinal anesthesia. The exact mechanism whereby oral clonidine prolongs spinal anesthesia remains to be determined.
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Sevoflurane has low blood and tissue solubility and is metabolized to free fluoride and hexafluoroisopropanol (HFIP). Although sevoflurane uptake and distribution and fluoride formation have been described, the pharmacokinetics of HFIP formation and elimination are incompletely understood. This investigation comprehensively characterized the simultaneous disposition of sevoflurane, fluoride, and HFIP. ⋯ Sevoflurane was rapidly metabolized to fluoride and HFIP, which was rapidly glucuronidated and eliminated in the urine. The overall extent of sevoflurane metabolism was approximately 5%.
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Minimum alveolar concentration (MAC) is decreased in pregnancy, but it is not known how quickly after delivery MAC returns to normal. We measured the MAC of isoflurane in a group of women undergoing elective tubal ligation after delivery. ⋯ The MAC of isoflurane was reduced in women 24-36 h postpartum and gradually increased to normal values by 72 h postpartum.