On-line pharmacokinetic parameter estimation for adaptive control of antiarrhythmic drug infusion

The use of an adaptive model-based controller for the infusion of procainamide in dogs was tested. This system uses five plasma samples of drug concentration during a 1-h infusion to automatically correct the model parameters of the computerized controller using a unique online parameter estimation scheme. Rapid feedback of plasma levels (less than 2.5 min) is achieved using a microfiltration plasma separator and enzyme immunoassay techniques. This system was tested in three animal studies and results were compared with those obtained in open-loop model-based infusions. One hour into the infusion, the average absolute error achieved with the open-loop system was 5.5 mg/l from a target concentration of 8 mg/l. By using the adaptive system, this was reduced to 0.8 mg/l. It is concluded that adaptive drug infusions are feasible to implement and provide a significant improvement over open-loop techniques for aggressive antiarrhythmic drug therapy