Design of Impulsive Feedback Controller for Dosing

This paper proposes a pulse-modulated controller that generates, under stationary conditions, a desired sequence of uniform and equidistant impulsive control actions from continuous measurements of the output of a smooth nonlinear time-invariant positive single-input single-output plant of Wiener structure. The proposed controller is applied to the dosing of the drug atracurium in closed-loop neuromuscular blockade and its performance is studied on a database of patient-specific pharmacokinetic-pharmacodynamic models previously estimated from clinical data.