A technique for approximately maintaining constant plasma levels of intravenous drugs

There is increasing interest among anesthesiologists in the use of continuous infusion of intravenous drugs. The therapeutic effect of most drugs is a function of the concentration at the site of drug effect, which in turn is determined by the plasma concentration. Constant plasma concentrations can be maintained by computer-controlled infusion pumps. However, such equipment is not yet widely available and will be expensive.

A technique is presented to enable the anesthesiologist to maintain approximately a desired plasma concentration after an arbitrary bolus dose by using a series of infusions with rates decreasing in a stepwise fashion. The algorithm is based on approximating the exact infusion needed to maintain the target plasma concentration by producing this concentration at discrete, specific times. Equations are derived for calculating the sequential rates of the infusion scheme. The equations assume linear pharmacokinetics, and the starting point for derivation of the equations is the assumption that the plasma concentration is given by the convolution of the drug infusion and the unit dose-response function.

The accuracy of the technique was assessed by simulating the infusion of fentanyl and midazolam. By using an infusion scheme of three steps, the error was no greater than 38% for fentanyl and no greater than 10% for midazolam.

Other than the assumption of linear kinetics, the algorithm is independent of pharmacokinetic models. Implementation does not require computer-based numerical analysis.