Open loop control of multiple drug effects in anesthesia.

Current open-loop computer-controlled infusion pumps do not explicitly control the transient adverse side effects of intravenous drugs during anesthesia. We used optimal control principles to synthesize a single-input multiple-output controller that regulates concentrations at the site of desirable drug effect while penalizing excessive side-effect drug concentrations. The cost function incorporates model-based predictions of future effect-site concentrations, and the capability of the anesthesiologist to anticipate upcoming surgical events. The controller was evaluated and then compared with alternative control strategies through computer simulation of a physiologically based pharmacokinetic model for the intravenous drug alfentanil. Multiple-effect control offers an analytic approach to limit the overshoot in adverse side-effect concentrations at the consequence of increasing the time to achieve the desired drug effect.