Semi-Adaptive Closed-Loop Control for Infusion of Medications with Transport Delay in Clinical Effects

[+] Author and Article Information
Xin Jin

Department of Mechanical Engineering, University of Maryland, 2107B Glenn L. Martin Hall, University of Maryland, College Park, MD 20742, USA

Chang-Sei Kim

School of Mechanical Engineering, Chonnam National University, Gwangju, Korea, Engineering 1A-421, Yongbong-Ro 77, Book-Ku, Gwangju, Korea

Steven Shipley

Department of Pathology and Laboratory Medicine, University of North Carolina, Campus Box #7525, Brinkhous-Bullitt Building, Chapel Hill, NC 27599-7525, USA

Guy A. Dumont

Department of Electrical and Computer Engineering, University of British Columbia, 3023 - 2332 Main Mall, Vancouver BC V6T 1Z4, Canada

Jin-Oh Hahn

Member, ASME, Department of Mechanical Engineering, University of Maryland, 2104C Glenn L. Martin Hall, University of Maryland, College Park, MD 20742, USA

1Corresponding author.

ASME doi:10.1115/1.4042686 History: Received August 27, 2018; Revised January 21, 2019


This paper presents a semi-adaptive closed-loop control approach to autonomous infusion of medications exhibiting significant transport delay in clinical effects. The basic idea of the approach is to enable stable adaptive control of medication infusion by (1) incorporating transport delay explicitly into control design by way of a Padé approximation while (2) facilitating linear parameterization of control design model by de-sensitization of nonlinearly parameterized cooperativity constant associated with pharmacodynamics. A novel dynamic dose-response model for control design is presented, in which the cooperativity constant exerts zero influence on the model output in the steady state. Then, an adaptive pole placement control technique was employed to fulfill adaptive control design in the presence of non-minimum phase dynamics associated with the Padé approximation of transport delay. The controller was evaluated in-silico using a case study of regulating a cardiovascular variable with a sedative under a wide range of transport delay and pharmacological profiles. The results suggest that adaptation of transport delay and pharmacological characteristics may be beneficial in achieving consistent and robust regulation of medication-elicited clinical effects.

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