Ademhalingsstudie naar de interactie tussen remifentanil en propofol in gezonde vrijwilligers.

A study aimed at PK-PD modelling of the respiratory effects of propofol in healthy volunteers in different plasma target concentrations, with and without a background infusion of remifentanil.

A mathematically correct PK-PD model will be developed that describes the depressant effect of propofol on breathing with and without a background of remifentanil.

First run:

30 minutes infusion of 3 three steps of 10 minutes in different Plasma Target Concentrations (0.7, 1.4, 2,1 ng/ml). Heartrate, saturation, EEG/BIS will be measured continously. Bloodsampling will be performed at baseline, 2 minutes after a step change, 5 minutes after a stepchange and just prior to a stepchange (app. at 10 minutes). Bloodsampling will be continued at intervals of 10 minutes untill 30 minutes after the end of the infusion.

After a 2 hr break we will perform the second run.
The second run will be identical to the first, except for a steady state background infusion of remifentanil at 0.8 or 1.6 ng/ml.

24 volunteers will participate in two experimental runs lasting about 1 hr with a 2 hr washout period in between.
During each experimental run a 30 minutes infusion of propofol (first run) or propofol + a steady state background of remifentanil (second run) will be performed. The propofol infusion will be divided in three steps (Target Plasma Concentration of 0.7, 1.4 or 2.1 mcg/ml) that will be administrated in a randomized order. All subjects will receive all steps in propofol. The remifentanil infusion will be a steady state infusion of 0.8 ng/ml or 1.6 ng/ml. This will be randomized and each volunteer will receive one of these background infusion levels. After the 30 minutes infusion an additional 30 minutes of data sampling will be performed for the washout period.

We will perform bloodsampling regularly via an arterial line. Furthermore we will measure ventilation and EEG via BISmonitoring.