Clinical pharmacokinetics of propofol given as a constant-rate infusion and in combination with epidural blockade.

STUDY OBJECTIVES

To investigate the pharmacokinetics of propofol in combination with epidural anesthesia or with intravenous (i.v.) alfentanil infusion, and to investigate the clinical feasibility of this anesthetic technique in lower abdominal surgery.

DESIGN

Randomized, open clinical study.

SETTING

Operating theaters and postanesthesia recovery unit at the department of gynecology of a university medical center.

PATIENTS

20 healthy, consenting ASA physical status I and II adult female patients undergoing lower abdominal surgery.

INTERVENTIONS

A total i.v. anesthetic technique was used in all patients. In Group 1, a continuous infusion of propofol was combined with an epidural block with bupivacaine. Group 2 patients received a combination of propofol and alfentanil infusions.

MEASUREMENTS AND MAIN RESULTS

The pharmacokinetics of propofol are best fitted to a two-compartment open model and were similar in both patient groups. Propofol blood clearance was 29.8 +/- 6.51 ml/min/kg, and volume of distribution was 3.60 +/- 1.34 L/kg, resulting in a blood elimination half-life of 144 +/- 46 minutes. The entire period of anesthesia was stable in the alfentanil group. In the epidural group, the initial period of anesthesia was too light as judged by the autonomic response to tracheal intubation, which also correlated in time to a lower propofol blood concentration than was seen in the alfentanil group. No evidence was found that an epidural block induced a change in propofol kinetics, apart from the lower blood concentration during the initial period of anesthesia.

CONCLUSIONS

We could not show any statistically significant influence of an epidural blockade on the pharmacokinetic parameters of propofol. Nevertheless, the concentration-time profile changed during infusion, rendering the described infusion regimen, in combination with epidural anesthesia, unsatisfactory for adequate hypnosis. The propofol infusion regimen combined with alfentanil provided immediate and stable blood concentrations that were adequate for surgery.