Plasma concentrations of etomidate during an intravenous infusion over 48 hours

Two groups of six patients who had undergone major maxillofacial surgery and who required intermittent positive pressure ventilation, analgesia and sedation for about 48 hours postoperatively were studied. Analgesia in the postoperative period was maintained by an infusion of fentanyl 0.034 micrograms/kg/minute. Sedation was maintained with an intravenous infusion of etomidate such that the patients slept but opened their eyes when addressed and obeyed commands. An assay method was developed which enabled the measurement of plasma concentration of etomidate for periods of up to 24 hours after stopping the infusion. The steady state plasma concentration associated with the technique which produced the required degree of sedation was found to be 158 micrograms/litre (SEM 36). Etomidate exhibited linear pharmacokinetics and the decrease in plasma concentration of etomidate after stopping the infusion was consistent with a three-compartment pharmacokinetic model. All the patients recovered within 1 hour of stopping the infusion. The use of results obtained from the first group of six patients enabled a dosage regimen to be calculated that used a two stage infusion. This regimen enabled a reduction in the time taken to establish the appropriate degree of sedation in the second group of six patients. The two-stage infusion technique provides a means of rapid sedation and of maintaining a suitable clinical response for the prolonged periods that may be necessary when patients are transferred to an intensive therapy unit.