SEMI-ADAPTIVE INFUSION CONTROL OF MEDICATIONS WITH EXCITATORY DOSE-DEPENDENT EFFECTS
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This thesis presents a semi-adaptive closed-loop control approach to infusion of medications that exhibit excitatory dose-dependent effects. A unique challenge associated with closed-loop control of such medications is that the upper bound of medication-induced excitatory response is unknown and cannot be readily incorporated into control design. To address this challenge, we developed a new dose-response model by extending a classical dose-response model, used for medications with depressive effects, by a nonlinear transformation, and extended a semi-adaptive control approach developed in our prior work, applicable to depressive dose-response relationship, to the new dose-response model. Two key advantages of the proposed model are that it can capture dose-response relationship from baseline to a target set point, and that it enables linear parameterization, thereby facilitating the control design task. We examined the efficacy of the proposed approach using an example of heart rate response to a vasoactive medication norepinephrine. System identification analysis using experimental data and in-silico controller testing showed that the new dose-response model could faithfully reproduce the experimental data, and that the semi-adaptive controller could effectively regulate the response in a wide range of simulated subjects.