The Influence of the dose on the Time to Peak Effect of Propofol:
Preliminary Results

Farid Garoud, Pierre-Yves Leuquueux, Gilbert Bejjani, Luc Barvais

Free University of Bruxelles, Bruxelles

Background and Goal of Study

Pharmacodynamic (PD) models of propofol are usually described as a first order process with one equilibration rate constant (Ke0) and two compartments (plasma and effect-site)1. With various results, several studies suggested that propofol PD could not be a first order process2,3. The time to peak effect of propofol is a model independent parameter which is known not to vary with the dose, when given as a bolus1. But this assertion is valid only if the PD of propofol is a first order process. The present study measures the time to peak effect of propofol with 2 different bolus doses.

Materials and Methods

After approval of local ethical committee and informed and written consent, 16 ASA I/II patients aged less than 50 were randomly assigned to 2 groups in a blinded manner to receive a bolus dose of propofol of either 1 mg/kg (group A) or 3 mg/kg (group B). BIS (Aspect Medical Systems, Nattick,MA) was recorded every 2 seconds and the time between the propofol bolus and the lowest BIS value minus 10 seconds (mean time for BIS processing) was considered as the time to peak effect.

Results and Discussions

There was no significant difference between group A and B regarding age (41 ± 6 vs 35 ± 8 yr respectively), sex (2 males and 6 females in both groups), weight (67 ± 16 vs 68 ± 20 kg) and height (163 ± 9 vs 168 ± 13 cm).

As expected, the minimum BIS value was significantly lower after a bolus dose of propofol of 3 mg/kg (17 ± 10) than after a dose of 1 mg/kg (47 ± 13) (p<0.05), but this value was obtained significantly later (113 ± 41 sec vs 78 ± 14 sec : p<0.05). This observation cannot be described with a direct PD model. (Values are mean ± SD).

Conclusion(s)

The time to peak effect of propofol varies with the bolus dose suggesting that the PD of propofol may not be a first order process and that the research into a new indirect PD model should be considered.

References

1. Minto CF et al. Anesthesiology 2003; 99:324-33

2. Stokes DN, Hutton P. Anesth Analg 1991; 74:316-7

3. Doufas AG et al. Anesthesiology 2004; 101:1112-21