Solvability of The Output Corridor Control Problem by Pulse-Modulated Feedback

TL;DR

This paper proves that for certain third-order systems, pulse-modulated feedback can always keep the output within a desired corridor, and applies this to assess the safety of drug dosing models in medicine.

Contribution

It establishes the solvability of the output corridor control problem for specific third-order systems using pulse-modulated feedback and applies it to pharmacokinetic-pharmacodynamic models.

Findings

Pulse-modulated feedback guarantees control for certain third-order systems.

Feasibility of drug dosing models depends on nonlinear pharmacodynamic parameters.

Low nonlinear parameters can lead to infeasibility in controlling drug effects.

Abstract

The problem of maintaining the output of a positive time-invariant single-input single-output system within a predefined corridor of values is treated. For third-order plants possessing a certain structure, it is proven that the problem is always solvable under stationary conditions by means of pulse-modulated feedback. The obtained result is utilized to assess the feasibility of patient-specific pharmacokinetic-pharmacodynamic models with respect to patient safety. A population of Wiener models capturing the dynamics of a neuromuscular blockade agent is studied to investigate whether or not they can be driven into the desired output corridor by clinically acceptable sequential drug doses (boluses). It is demonstrated that low values of a parameter in the nonlinear pharmacodynamic part lie behind the detected model infeasibility.