Anesthesiology
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Randomized Controlled Trial Clinical Trial
Population pharmacokinetic modeling in very premature infants receiving midazolam during mechanical ventilation: midazolam neonatal pharmacokinetics.
Midazolam is used widely as a sedative to facilitate mechanical ventilation. This prospective study investigated the population pharmacokinetics of midazolam in very premature infants. ⋯ Serum concentration-time data were used in modeling the population pharmacokinetics of midazolam in very premature, ventilated neonates. Clearance of midazolam was markedly decreased compared with previous data from term infants and older patients. Infants weighing less than 1,000 g at birth had significantly lower clearance than those weighing more than 1,000 g.
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Comparative Study
The comparative pharmacodynamics of remifentanil and its metabolite, GR90291, in a rat electroencephalographic model.
The purpose of this study was to investigate the in vivo pharmacodynamics and the pharmacodynamic interactions of remifentanil and its major metabolite, GR90291, in a rat electroencephalographic model. ⋯ Analysis of the data on the basis of a previously postulated, mechanism-based pharmacokinetic-pharmacodynamic model for synthetic opioids revealed that the low in vivo potency of GR90291 can be explained by a low affinity to the mu-opioid receptor in combination with a poor brain penetration.
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There are no adequate pharmacodynamic data relating concentrations of acetaminophen in serum to analgesia. ⋯ The pharmacodynamics of acetaminophen can be described using a sigmoidal Emax model with a low Hill coefficient. To achieve a mean posttonsillectomy pain score of 3.6 of 10, an effect compartment concentration of 10 mg/l is necessary.
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Capsaicin, the pungent ingredient in chili peppers, is a vanilloid with noxious and analgesic effects that inhibits tetrodotoxin-resistant sodium currents. Because tetrodotoxin-resistant currents are found primarily in small-diameter nociceptor afferents of the peripheral nerves, their inhibition may lead to selective analgesia. Therefore, the authors evaluated the interactions between tetrodotoxin, a site 1 sodium channel blocker, and capsaicin on nerve blockade in vivo. ⋯ Site 1 sodium channel blockers and vanilloids have synergistic effects on nerve blockade in vivo. These interactions may be useful in developing prolonged local anesthetics and elucidating mechanisms of functionally selective nerve blockade.
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It is not known whether the lungs influence the early pharmacokinetics of muscle relaxants and, if they do, whether differences in pulmonary uptake contribute to the differences in potency and/or onset time among muscle relaxants. Because the lungs are uniquely positioned, receive the entire cardiac output, have a large capillary surface area, and can temporarily store various basic drugs, the authors determined whether substantial pulmonary first-pass uptake of muscle relaxants occurs. ⋯ There is no substantial pulmonary first-pass uptake of rocuronium, vecuronium, Org 9487, Org 7617, or d-tubocurarine in pigs. Therefore, differences in pulmonary first-pass uptake do not contribute to the differences in potency and/or onset time among muscle relaxants.