Anesthesiology
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Mivacurium is hydrolyzed by the butyrylcholinesterase enzyme, and patients with hereditary changes of the enzyme often have prolonged duration of action of mivacurium. In this study, the authors investigated the significance of the most commonly occurring variant, the Kalow (K) variant, established using DNA analysis, for the response to mivacurium. ⋯ The K variant prolongs the duration of action of mivacurium. The current results indicate that the effect is modest when the K variant occurs heterozygously with the wild type or the A variant but is marked in patients who are homozygous for both the A and K variants.
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Target-controlled infusion (TCI) drug delivery systems deliver intravenous drugs based on pharmacokinetic models. TCI devices administer a bolus, followed by exponentially declining infusions, to rapidly achieve and maintain pseudo-steady state drug concentrations in the plasma or at the site of drug effect. Many studies have documented the prediction accuracy of TCI devices. The authors' goal was to apply linear systems theory to characterize the relation between the variability in concentrations achieved with TCI devices and the variability in concentrations after intravenous bolus injection. ⋯ TCI devices neither create nor eliminate biologic variability. For any drug described by linear pharmacokinetic models, no infusion regimen, including TCI, can have higher variability than that observed after bolus injection. The median performance of TCI devices should be reasonably close to the prediction of the device. However, the overall spread of the observations is an intrinsic property of the drug, not the TCI delivery system.
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Some patients treated with ondansetron for postoperative nausea and vomiting do not respond to therapy. One possible mechanism for this failure is ultrarapid drug metabolism via the cytochrome P-450 system, specifically the enzyme 2D6 (CYP2D6). Ultrarapid metabolism is seen in patients with multiple functional copies (>/= 3) of the CYP2D6 allele. This study was designed to determine whether patients who were given prophylactic ondansetron and had multiple CYP2D6 alleles had an increased rate of postoperative nausea and vomiting. ⋯ Patients with three copies of the CYP2D6 gene, a genotype consistent with ultrarapid metabolism, or both have an increased incidence of ondansetron failure for the prevention of postoperative vomiting but not nausea.
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Some studies suggest that behavioral complications of cholestasis, such as fatigue and pruritus, may be associated with altered neurotransmission in the brain. Because inhaled anesthetics primarily act on ion channels and receptors on the neuronal cell membrane and alter synaptic transmission in the central nervous system, it is possible that altered sensitivity to inhaled anesthetics may occur in cholestatic patients. Therefore, the authors compared the minimum alveolar concentration (MAC)-awake of desflurane in obstructive jaundiced patients with the MACawake in nonjaundiced patients. ⋯ The MACawake of desflurane is reduced in obstructive jaundiced patients compared with nonjaundiced controls.