Continuous i.v. infusion of labetalol for postoperative hypertension. Haemodynamic effects and plasma kinetics

Labetalol is a combined alpha- and beta-adrenoreceptor blocking agent. A loading dose may be used to antagonize sympathetic overactivity rapidly after surgery and be followed by a continuous infusion to achieve a stable effect. The haemodynamic effects and pharmacokinetics of this method of labetalol administration were studied in six rewarmed, extubated and sedated patients 15 +/- 2 h after aortobifemoral bypass surgery. Patients were monitored with radial and thermistor-tipped pulmonary artery catheters. Labetalol 1.5 mg kg-1 was injected i.v. over 5 min and a maintenance infusion of 0.2 mg kg-1 h-1 was started 30 min later and continued for 5.5 h. Within 5 min of the loading dose, i.v. labetalol induced significant (P less than 0.05) decreases in mean arterial pressure (-32 +/- 11%), in heart rate (-20 +/- 11%) and in cardiac index (-26 +/- 15%) that lasted throughout the infusion. Changes in systemic vascular resistance were not uniform, but an increase was not observed in any patient. Mean stroke volume index and ventricular filling pressures were not significantly affected by labetalol administration. The mean measured steady state plasma concentration (Css) (264 +/- 46 ng ml-1) was higher than predicted (170 ng ml-1) because the clearance (13.1 +/- 2.4 ml kg-1 min-1) was lower than that used to calculate the infusion rate. We conclude that labetalol is an effective antihypertensive agent in the postoperative period. A Css can be achieved rapidly by such i.v. administration and this offers the advantage of inducing rapid and stable haemodynamic effects.(ABSTRACT TRUNCATED AT 250 WORDS)