Taoufik Wassar, Tam´s Luspay, Kallu R. Upendar, Marc Moisi, Richard B. Voigt, Nicole R. Marques, Muzna N. Khan, Karolos M. Grigoriadis, Matthew A. Franchek, and George C. Kramer
Closed-loop drug delivery, hypotensive patient, blood pressuredynamic modelling, anti-windup PI controller
Developed in this paper is an automated closed-loop system that regulates the target blood pressure and maintains haemodynamic stability in hypotensive patients using the vasopressor drug phenylephrine. First, experimental studies are conducted on several healthy swine to identify dynamic mathematical models that quantify and predict blood pressure response to infusion of vasopressors. A first-order plus time-delay model structure has been selected to capture mean arterial pressure (MAP) response of patient’s subject to drug injection. Intra- and inter-patient variabilities of the model parameters have been identified and characterized. Then, an anti-windup proportional integral controller is designed, taking patient response variation in account. A nonlinear stochastic simulation environment has been developed to investigate the controller under diverse scenarios. Finally, automatic control of blood pressure is applied for the treatment of eight anesthetized swine subjected to hypotension induced by standard haemorrhage, spinal cord injury, and vasodilator injection. Results from clinical evaluations show that the proposed automated closed-loop control system is able to keep MAP near target and its performance is superior to that of manual control of infusion.
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