Estimation of the Plasma Effect Site Equilibration Rate Constant (ke0) of Propofol in Children Using the Time to Peak Effect

Abstract

Background Targeting the effect site concentration may offer advantages over the traditional forms of administrating intravenous anesthetics. Because the lack of the plasma effect site equilibration rate constant (ke0) for propofol in children precludes the use of this technique in this population, the authors estimated the value of ke0 for propofol in children using the time to peak effect (tpeak) method and two pharmacokinetic models of propofol for children. Methods : The tpeak after a submaximal bolus dose of propofol was measured by means of the Alaris A-Line auditory evoked potential monitor (Danmeter A/S, Odense, Denmark) in 25 children (aged 3-11 yr) and 25 adults (aged 35-48 yr). Using tpeak and two previously validated sets of pharmacokinetic parameters for propofol in children, Kataria's and that used in the Paedfusor (Graseby Medical Ltd., Hertfordshire, United Kingdom), the ke0 was estimated according to a method recently published. Results The mean tpeak was 80 +/- 20 s in adults and 132 +/- 49 s in children (P < 0.001). The median ke0 in children was 0.41 min(-1) with the model of Kataria and 0.91 min(-1) with the Paedfusor model (P < 0.01). The corresponding t1/2 ke0 values, in minutes, were 1.7 and 0.8, respectively (P < 0.01). Conclusions : Children have a significantly longer tpeak of propofol than adults. The values of ke0 of propofol calculated for children depend on the pharmacokinetic model used and also can only be used with the appropriate set of pharmacokinetic parameters to target effect site in this population.