Exploring the Plasma-Effect Site Concentration Difference During Effect Site Controlled Infusion

Abstract

Based on pharmacokinetic models, target-controlled infusion (TCI) systems have been developed to reach and maintain any desired plasma concentration of a drug during anaesthesia. These TCI systems control the plasma concentration and clinical effects are often deferred. The delay between the peak plasma concentration (Cpmax) and maximal clinical effect is called hysteresis. To explain this hysteresis, a new compartment has been added to the pharmacokinetic model; the effect compartment (see the chapter by Bovill). To characterise the rate of distribution elimination of intravenous anaesthetic drugs to and from the effect compartment parameters derived from the EEG such as the spectral edge and the bispectral index have been used. For a drug, if the plasma concentration is at a semi-steady state, the concentration in the effect compartment (Ce, effect site concentration) will rise following a simple increasing exponential curve. The effect site concentration is proportional to the plasma concentration: Cp. (1-e-kt). The effect site concentration is characterised by the quantity of drug entering the effect compartment. The effect site concentration depends on the gradient between the plasma and the effect site concentration and by the value of the elimination rate constant of the effect compartment (ke0). The ke0 value is different for each drug but is fixed in a specific pharmacokinetic model for one drug. For a plasma concentration at steady state, the required time needed to obtain Ce = 1/2 Cp is called T1/2ke0.