The influence of epidural blockade with ropivacaine on the pharmacokinetics and pharmacodynamics of propofol sedation

Recently, various studies report on the hypnotic sparing effect of central
neuraxis blockade. Local anaesthetics have been shown to enhance sedation and
reduce the hypnotic dose requirements.Up until now, the mechanism and the
magnitude of the sedative sparing effect of central neuraxis blockade remain
unclear.
The pharmacokinetics of intravenous sedatives may be affected by an epidurally
induced change in distribution or clearance of these agents, the
pharmacodynamics of intravenous agents may be affected through the
deafferentation that occurs when central neuraxis blockade is installed.
We propose to study the influence of epidural blockade with ropivacaine on the
pharmacokinetics and pharmacodynamics of propofol when given as intravenous
premedication.

1.To evaluate the influence of epidural blockade with ropivacaine on the
pharmacokinetics of propofol.
2.To evaluate the influence of epidural blockade with ropivacaine on the
pharmacodynamics of propofol. This includes both the sedative and the
hemodynamic effects.

randomized, double-blind, placebo-controlled

There are 4 groups of 7 patients. The patients in group 1 will receive no
ropivacaine (10 ml of epidural NaCl 0.9%), the patients in group 2 will receive
50 mg of epidural ropivacaine 7.5 mg/ml, the patients in group 3 will receive
100 mg of epidural ropivacaine 7.5 mg/ml and the patients in group 4 will
receive 150 mg of ropivacaine 7.5 mg/ml.
After the epidural blockade has reached its maximal level. Patients will
receive a target controlled infusion with propofol with an initial target
concentration of 1 µg/ml. After 6, 12 and 18 min this target propofol
concentration will be increased to 2.5 µg/ml, 4 µg/ml and 6 µg/ml. Every 3rd
min, the Ramsay sedation score, the eyelash reflex, the BIS score and state of
consciousness will be tested and an arterial blood sample will be taken for
blood propofol concentration determination. After the loading dose ropivacaine
epidurally we will take according to a predetermined blood sampling schedule
samples to determine the ropivacaine plasma concentrations.

The intravenous line is included in the standard anaesthetic care for scheduled
surgical procedures. The arterial will be placed for study purposes. Due to the
venous and/or arterial line some bruising may occur. In this study, duration of
venous line placement will not prolong the normal stay of lines. The arterial
line will be removed directly after termination of the study.