Anesthesiology
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Clinical Trial
Methadone Pharmacogenetics: CYP2B6 Polymorphisms Determine Plasma Concentrations, Clearance, and Metabolism.
Interindividual variability in methadone disposition remains unexplained, and methadone accidental overdose in pain therapy is a significant public health problem. Cytochrome P4502B6 (CYP2B6) is the principle determinant of clinical methadone elimination. The CYP2B6 gene is highly polymorphic, with several variant alleles. CYP2B6.6, the protein encoded by the CYP2B6*6 polymorphism, deficiently catalyzes methadone metabolism in vitro. This investigation determined the influence of CYP2B6*6, and other allelic variants encountered, on methadone concentrations, clearance, and metabolism. ⋯ CYP2B6 polymorphisms influence methadone plasma concentrations, because of altered methadone metabolism and thus clearance. Genetic influence is greater for oral than IV methadone and S- than R-methadone. CYP2B6 pharmacogenetics explains, in part, interindividual variability in methadone elimination. CYP2B6 genetic effects on methadone metabolism and clearance may identify subjects at risk for methadone toxicity and drug interactions.
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Cesarean delivery (CD) is associated with significantly increased risks of anesthesia-related adverse events (ARAEs) and nonanesthetic perioperative morbidity compared with vaginal delivery. Temporal trends in these adverse outcomes remain unknown despite efforts to improve maternal safety. This study examines temporal trends in ARAEs and nonanesthetic perioperative complications in CDs in New York hospitals. ⋯ Anesthesia-related outcomes in cesarean deliveries appear to have improved significantly across hospitals in New York in the past decade. Perioperative nonanesthetic complications remain a serious healthcare issue.
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Critical illness is likely associated with an increased risk of dementia, but the magnitude remains uncertain. ⋯ Elderly critical care survivors have a 60% increased relative risk, but only 3% increased absolute risk, of receiving a diagnosis of dementia in the subsequent 3 yr compared with the general population. This increased risk is not accounted for by risk factors preexisting the critical illness. Surveillance bias, which increases the likelihood of receiving a diagnosis of dementia, could account for some or all of these additional risks.
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Retrospective studies in humans have shown a higher prevalence of learning disabilities in children that received multiple exposures to general anesthesia before the age of 4 yr. Animal studies, primarily in rodents, have found that postnatal anesthetic exposure causes neurotoxicity and neurocognitive deficits in adulthood. The authors addressed the question of whether repeated postnatal anesthetic exposure was sufficient to cause long-term behavioral changes in a highly translationally relevant rhesus monkey model, allowing study of these variables against a background of protracted nervous system and behavioral development. ⋯ Increased emotional behavior in monkeys after anesthesia exposure in infancy may reflect long-term adverse effects of anesthesia.