Anesthesiology
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Randomized Controlled Trial Clinical Trial
The role of cytochrome P450 3A4 in alfentanil clearance. Implications for interindividual variability in disposition and perioperative drug interactions.
There is considerable unexplained variability in alfentanil pharmacokinetics, particularly systemic clearance. Alfentanil is extensively metabolized in vivo, and thus systemic clearance depends on hepatic biotransformation. Cytochrome P450 3A4 was previously shown to be the predominant P450 isoform responsible for human liver microsomal alfentanil metabolism in vitro. This investigation tested the hypothesis that P450 3A4 is responsible for human alfentanil metabolism and clearance in vivo. ⋯ Modulation of P450 3A4 activity by rifampin and troleandomycin significantly altered alfentanil clearance and disposition. These results strongly suggest that P450 3A4 is the major isoform of P450 responsible for clinical alfentanil metabolism and clearance. This observation, combined with the known population variability in P450 3A4 activity, provides a mechanistic explanation for the interindividual variability in alfentanil disposition. Furthermore, known susceptibility of human P450 3A4 activity to induction and inhibition provides a conceptual framework for understanding and predicting clinical alfentanil drug interactions. Finally, human liver microsomal alfentanil metabolism in vitro is confirmed as an excellent model for human alfentanil metabolism in vivo.
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Randomized Controlled Trial Multicenter Study Clinical Trial
Remifentanil versus remifentanil/midazolam for ambulatory surgery during monitored anesthesia care.
This study was designed to define the appropriate dose of remifentanil hydrochloride alone or combined with midazolam to provide satisfactory comfort and maintain adequate respiration for a monitored anesthesia care setting. ⋯ Remifentanil alone or combined with midazolam provided adequate analgesia and maintained adequate respiration at the doses reported. The low dose of remifentanil combined with 2 mg midazolam, compared with remifentanil alone, resulted in fewer side effects, slightly greater sedation, and less anxiety.
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Randomized Controlled Trial Clinical Trial
Intracuff pressures do not predict laryngopharyngeal discomfort after use of the laryngeal mask airway.
The laryngeal mask airway (LMA) is a large foreign body that exerts pressure on the pharyngeal mucosa, which may lead to throat discomfort. To determine whether intracuff pressures are associated with such discomfort, a randomized, double-blind study was performed to determine the effect of high versus low intracuff pressures. ⋯ Differences in LMA intracuff pressures did not influence either the incidence or severity of laryngopharyngeal complaints.