Patient-controlled analgesic therapy, Part IV: pharmacokinetics and analgesic plasma concentrations of morphine.

The influence of anaesthesia and surgery on the pharmacokinetics of morphine was studied in 10 patients. Plasma concentrations of morphine were assayed by gas chromatography with electron capture detection. All patients were studied on the day of surgery and again 3 to 7 days later. Mean +/- SD for peroperative Vd(area) was 6.3 +/- 3.6 L/kg and for the terminal half-life was 3.8 +/- 2.3 h. In the postoperative period, Vd(area) decreased to 3.7 +/- 1.4L/kg and the terminal half-life to 2.2 +/- 1.1 h. Plasma clearance (Clp) remained constant, peroperative Clp being 20 +/- 7.0 ml/min/kg and postoperative Clp 21 +/- 6.0 ml/min/kg. Postoperative pain was relieved by patient-controlled administration of intravenous doses of morphine by means of a programmable drug injector. The mean morphine consumption was 2.6 +/- 1.2 mg/h, which produced a mean plasma concentration of 21 +/- 12 ng/ml with a calculated mean minimum effective concentration (MEC) of 16 +/- 9 ng/ml. In 1 patient, temporary hypercapnia was seen during a period of hypovolaemia. Analgesia was considered satisfactory by all patients.