The pharmacokinetics of midazolam during total i.v. anaesthesia were determined in 15 female patients undergoing major surgery. Midazolam was administered together with an analgesic drug and a neuromuscular blocking drug. The dose regimen of midazolam, based on simulations, included two consecutive infusions following a bolus injection at the induction of anaesthesia. Multiple blood samples were drawn and a two-compartment open model was fitted to the measured plasma concentrations. Plasma clearance (483 ml min-1), apparent volume of distribution (1.94 litre kg-1) and terminal half-life (3.1 h) were in agreement with other reports. Thus, there was no obvious evidence that the surgical procedure or the concomitant use of other drugs, or both, influenced the pharmacokinetics of midazolam. The relatively rapid elimination makes midazolam suitable for use by infusion in a total i.v. technique.
Interactive group discussions with prescribing profiles were found to be useful in improving hospital specialists' adherence to guidelines. However, the effect on the overall adherence was modest, indicating the importance of clear messages for improvement and relevant guidelines for the prescribing of specialist drugs but also more precise methods for evaluating the effect of real-life-interventions.
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