Abstract

Closed-loop controlled drug dosing has the potential of revolutionizing clinical anesthesia. However, inter-patient variability in drug sensitivity poses a central challenge to the synthesis of safe controllers. Identifying a full individual pharmacokinetic-pharmacodynamic (PKPD) model for this synthesis is clinically infeasible due to limited excitation of PKPD dynamics and presence of unmodeled disturbances. This work presents a novel method to mitigate inter-patient variability. It is based on: 1) partitioning an a priori known model set into subsets; 2) synthesizing an optimal robust controller for each subset; 3) classifying patients into one of the subsets online based on demographic or induction phase data; 4) applying the associated closed-loop controller. The method is investigated in a simulation study, utilizing a set of 47 clinically obtained patient models. Results are presented and discussed.Clinical relevance-The proposed method is easy to implement in clinical practice, and has potential to reduce the impact from surgical stimulation disturbances, and to result in safer closed-loop anesthesia with less risk of under- and over dosing.

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