A general solution for nonparametric control of a linear system using computer-controlled infusion pumps

Investigators have developed algorithms for use in computer-controlled infusion pumps (CCIPs) which dose intravenous drugs assuming multiexponential unit impulse response (UIR) function. However for many UIR multiexponential functions are at best an approximation. For almost all substances the early times after an impulse administration show complex profiles hardly described by multiexponential functions. For many later times also show departures from exponential decline. The authors derive a general approach for a CCIP which can be used with an arbitrary UIR function. A particular instance of the approach is based on a nonparametric representation of an UIR which uses spline functions. The approach is computationally simple, it can take into account desired constraints (for example no overshoot to avoid toxicity) and presents a solution to control concentrations of substances in a site different from the input site. Examples based on real lodocaine, veralipride, and thiopental data demonstrate the approach.