The Influence Of Propofol Administration Rate On The Ke0 Value. Preliminary Results 

Michel MRF Struys, MD,PhD ; Nicolaas De Neve, MD ; Tom De Smet, MSc ; Dorine Dyzers, CN; Eric P Mortier, MD, DSc and Steven L. Shafer, MD

Dep. of Anesthesia, Ghent University, Ghent, Belgium and #Dep. of Anesthesia, Stanford University, Palo Alto, Ca, USA

Background :

Propofol drug transfer between the plasma and effect-site can be modelled as a first-order process characterized by ke0. We studied the influence of the bolus administration rate on the value of ke0

Methods :

After IRB approval and written informed Consent, 60 female ASA 1 patients were randomly assigned to one of four groups to receive a 2.5 mg/kg propofol given as a bolus (as fast as possible) (Group 1), or given as an infusion in 1, 2 or 3 minutes (Groups 2, 3 or 4).  To monitor the propofol cerebral drug effect, BIS was continuously measured using an A-2000 monitor (version 4.0-XP, Aspect Medical, Natick, Ill.). Vital signs were measured using an Datex-Ohmeda S5-monitor. All data were recorded using RUGLOOP II software (Demed, Temse, Belgium). Propofol plasma concentrations were calculated every 10 seconds using an 3-compartmental model previously published by Schnider et al (1). For each group, the pooled ke0 value was calculated by collapsing the hysteresis loop between the predicted propofol plasma concentration and the BIS using NONMEM (2) and a dedicated mathematical solution developed by one of the co-authors (SLS). To take into account the delay in the BIS monitor, a delay time of 10 seconds was included. Simultaneously, an effect-site concentration profile for each patient was calculated. Post-hoc, the observed time required for reaching maximal drug effect (lowest BIS), called tpeak, BIS was compared to the predicted time required for reaching maximum propofol effect-site concentration, called tpeak, Ce .

Results :

For each group, tpeak, BIS, tpeak, Ce , and ke0 (mean ± SD) are shown in the table.

Discussion :

In contrast to previously hypothesis claiming an independency of the ke0 value to the propofol administration rate, we found a clear increase in ke0 at higher infusion rates. Overall, the predicted time course of drug effect as depicted by the effect-site concentration paralleled with the observed drug effect, measured with BIS. It can be concluded that the ke0 of propofol depends on the time course of drug delivery.

References :

 1) Schnider et al, Anesthesiology 1988, 88, 1170-82. 2) Bael et al. NONMEM User's guides. San Francisco, NONMEM Project Group, University of California, 1992