Postoperative sedation with propofol infusion: haemodynamics and pharmacokinetics

This study was designed to investigate the haemodynamic response and pharmacokinetics of a low-dose propofol continuous infusion in providing sedation in patients who required mechanical ventilation after coronary artery bypass grafting surgery.

22 male patients, aged between 45 and 65 years, were evaluated in an open, uncontrolled study.

At the end of the surgical procedure, a low-dose (1 mg/kg/h) propofol infusion was started and adjusted to optimise sedation according to the Ramsay scale. The mean propofol infusion rate was 1.42 +/- 0.4 mg/kg/h.

Electrocardiogram, systemic and pulmonary arterial pressure, and central venous pressure were monitored continuously. Left ventricular shortening fraction was calculated by transoesophageal echocardiography. Propofol plasma levels were calculated in 10 patients to evaluate the pharmacokinetics.

Throughout the duration of the study all patients were haemodynamically stable. Sedation was maintained for 363 +/- 244 minutes and was adequate in all patients. The clinical recovery time (postsedation responsiveness) was 15.7 +/- 6.2 minutes, after infusion suspension. There was no correlation between propofol plasma levels or propofol infusion rate and the depth of sedation (respectively, r = 0.39 and r = 0.23), while there was a good correlation (r = 0.62) between propofol infusion rate and plasma levels. Open two-compartment model pharmacokinetics were demonstrated.

Low-dose propofol infusion (1 to 2 mg/kg/h) proved to be well tolerated and effective in maintaining sedation after cardiac surgery. Sedation was quickly obtained without a propofol loading dose; steady-state plasma concentrations of 0.6 to 0.8 mg/L were rapidly achieved. Propofol pharmacokinetics ensure rapid clearance with rapid clinical recovery.