Estimation of the plasma-effect site equilibration rate constant (keO) of propofol by two methods

Pablo Sepulveda MD†, Luis I. Cortínez MD*, Gastón Núñez MD†, Alejandro Recart MD†

†Clinica Alemana-Universidad del Desarrollo, *Pontificia Universidad Católica de Chile

Runing Head: 
Propofol ke0 has been calculated using different methods and different EEG devices.

The plasma-effect site equilibration rate constant (keO) allows the determination of pharmacodynamic parameters of a drug and targeting the effect site instead of plasma concentration when administering intravenous anesthetics. A novel and simple method to calculate keO is the so called “tpeak method” [1] based on the time of maximum effect (tpeak) of a drug. This method has been recently used to calculate the keO of propofol in children [2], and validated over traditional ways to derive keO only in one study measuring rocuronium electromyographic effect. [3] Thus, the aim of this study is to compare the keO’s of propofol obtained by the “tpeak method” and that by the traditional non-parametric “loop collapsing” method using the Cerebral State Monitor (CSM) as the measured response.

Methods:

After routine non-invasive monitoring of arterial pressure, electrocardiogram, pulse oximetry, and consciousness (CSM) 13 ASA I patients, aged 33-56 yr, scheduled to undergo minor surgery under general anesthesia received a bolus dose of propofol 1.8 mg kg-1 in less than 5 seconds. The CSI response was automatically recorded every 1 second using the CSM software and a laptop until CSI spontaneously returned to basal values. The time to peak effect and the complete response curve of CSI were then used to calculate propofol, ke0s using the tpeak method and the non-parametric “loop-collapsing” method. The pharmacokinetic model published by Marsh was used to predict the plasma concentrations of propofol after the bolus dose in each patient. Caculations were made with the Solver function of Excel. The ke0s obtained by both methods were compared with Mann-Whitney´s test. A p value < 0.05 was considered significant. Values are median (range).

Results:

 keO was 0.98 min-1 (0.22-8.58) with “tpeak” and 0.56 min-1 (0.22-8.75) with the non parametric method. (NS).

Conclusions:

Although non-significant differences were found between the keOs estimated with both methods. (Possible β-error). This study suggest that the use of a “single point” of the response curve (tpeak) to calculate keO do not necessarily agree with the values obtained by the analysis of the complete response curve when the CSI is used as the measured response.

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

2.             Muñoz HR et al. Anesthesiology 2004; 101:1269-74.

3.             Cortínez L, Muñoz H (Abstract) ASA Annual meeting 2005.