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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.

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Fourteen patients with postoperative pain were allowed to self-administer preset doses of pethidine intravenously via a logic-controlled motor syringe. Plasma samples were collected during anaesthesia and the postoperative self-administration period, and the concentrations of pethidine and nor-pethidine were determined. Separate single-dose studies in eight patients yielded pharmacokinetic parameters which made possible computer simulations of continuous plasma concentration curves for the anaesthesia and postoperative self-administration period. The consumption of pethidine showed great interindividual variations with a mean consumption for the entire group of 26 mg per hour. The patients established steady-state plasma concentrations with far less than the maximum amount of pethidine allowed. The mean measured plasma concentration of pethidine which provided adequate analgesia was 738 +/- 149 ng/ml. Simulated and measured plasma concentrations were in close agreement. The individual mean drug consumption per hour during self-administration correlated closely with the individual elimination rate of pethidine. No serious side effects were observed. Thus, patient-controlled analgesic therapy offers an individualized analgesic supply to meet an analgesic demand which is governed by each patient's appreciation of pain.