Target controlled infusions: targeting the effect site while limiting peak plasma concentration

Background: Target controlled infusion (TCI) systems are available commercially worldwide, except in North America. Existing systems target the plasma drug concentration, which may be less than ideal because the plasma is not the site of drug effect. The commonly accepted existing algorithm to target the site of drug effect results in high plasma concentrations, which may increase the acute hemodynamic effects of intravenous anesthetic drugs. Methods: A novel mathematical algorithm is proposed for controlling the effect site concentration using a TCI device. The algorithm limits the peak plasma concentration, thereby slowing the onset of anesthetic drug effect but potentially ameliorating side effects. Simulations are used to examine the delay in time to peak effect for fentanyl, alfentanil, sufentanil, remifentanil, and propofol when the peak plasma concentration is limited by the algorithm. Results: The plasma overshoot required of the previously proposed algorithm to control the site of drug effect can be reduced by 60% with only about a 20% delay in the onset of drug effect. Conclusions: Concerns about the high plasma concentrations that result from targeting the effect site with a TCI device can be addressed by reducing the peak plasma concentration by as much as 60% with only a very modest increase in time to peak effect.