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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Electronic anesthesia record keeping (EARK) systems increasingly are used in the operating room, but studies have only recently begun to investigate their effect on anesthesia task performance. Teak analysis, workload assessment, and vigilance assessment techniques were used to study senior residents providing anesthesia for coronary artery bypass graft (CABG) procedures. The impact on anesthesia residents' workload of the routine use of transesophageal echocardiography (TEE) also was examined. ⋯ This study provides an objective description of the task distribution and workload during the administration of anesthesia for cardiac surgery. Under the conditions of this study. EARK use modestly decreased the time spent record keeping during the postintubation prebypass period. However, there was no effect of EARK either on vigilance or several measures of workload. TEE use was associated with increased workload and possibly decreased vigilance.
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Comparative Study
Assessment of the potency and intrinsic activity of systemic versus intrathecal opioids in rats.
One measure of an opioid's efficacy is its ability to retain its analgesic effect as the intensity of a noxious stimulus is increased. A few studies have assessed the ability of either spinal or systemic opioids to produce analgesia using low- and high-intensity stimulation. There are little data available to show whether there are differences in efficacy between systemic and intrathecal opioid administration. The purpose of this study was to assess the relative efficacy of several clinically useful opioids systemically and spinally and to determine whether intrathecal administration resulted in greater efficacy than systemic administration. ⋯ As intensity of noxious stimulation is increased, the more potent opioid agonists, administered systemically, produce antinociception with lesser increases in dose compared with lower potency drugs such as meperidine or morphine. When given spinally all opioid agonists tested, including morphine and meperidine, demonstrated good efficacy, as measured by their ability to provide antinociception for high versus low intensity stimulation.
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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.