Target Site

Blood vs. Effect-site control

• The effect-site concentration lags behind the plasma concentration because of the blood-brain barrier
• TCI systems can reduce this delay by raising the plasma concentration beyond the intended effect-site concentration. This then increases the gradient between plasma and effect site to “pressure” the drug into the effect site more quickly. Most drug TCI models now incorporate this option.
• Caveats
  • PK models can only predict the concentration achieved in plasma and effect site.
  • The plasma concentration can be verified by taking blood samples to compare the predicted with the actual concentration so that the precision and bias can be calculated.
  • However, the effect-site concentrations can not be measured but are estimated from the clinical effect. Models, therefore, often vary considerably in predicting effect-site concentrations.
  • Your patient’s pharmacokinetics and pharmacodynamics may also vary from the model
  • Using effect-site targeting results in higher plasma concentrations and may increase adverse effects e.g. hypotension
  • Careful titration and monitoring are required

Impact of Ke0

• Keo is a rate constant that describes the time lag between Cp and Ce
• Larger Ke0 = Shorter time lag
• Incorporating a smaller Ke0 results in a larger bolus to achieve the same Ce when compared to the same model using a larger Ke0
• TCI systems using the Marsh model often incorporate a larger Ke0 than originally intended to reduce the impact of a large bolus dose at induction
• This is still more accurate than the Schnider effect site model which overestimates the effect-site concentration much more than Marsh
• The Eleveld model, clinically, seems to be the most accurate in estimating effect-site
• It is difficult to know the “right” Ke0 – it is model specific and there are also inter-individual differences
• The following graphs reveal the difference between a small and large Ke0 TCI system on effect-site target at induction

• Caveats
  • If you are confused with Ke0, don’t worry!
  • When we talk about the TCI models and dosing, we will give you more guidance on models and techniques
• Ke0 is the parameter that should be considered when predicting loss and recovery of consciousness based on the effect-site concentration