Taoufik Wassar, Tamas G. Lupsay, Upendar R. Kallu, Marc Moisi, Richard B. Voigt, Nicole R. Marques, Muzna N. Khan, Karolos M. Grigoriadis, George C. Kramer, and Matthew A. Franchek
Closed-loop drug delivery, blood pressure dynamic modeling, anti-windup PI control
Hemodynamic stabilization of combat casualties with hemorrhagic shock often requires fluid resuscitation. However, rapid acting vasopressors are being used with increasing frequency to help maintain adequate perfusion of the brain and other vital organs, especially when hemodynamic stability is not maintained despite infusion of fluids. In this paper, a computerized decision support and fully autonomous closed-loop system to regulate the target blood pressure and to maintain hemodynamic stability is proposed. Two closed-loop algorithms using phenylephrine are designed and examined: anti-windup proportional integral control and adaptive internal model control. For analysis, design and evaluation dynamic mathematical models are identified to quantify mean arterial pressure response to phenylephrine using animal experiment data. A simple first-order time-delayed model is proposed. The controllers are first evaluated in a simulation environment, then implemented and validated in several animal experimental studies. Automatic control of blood pressure with anti-windup proportional integral control approach is used for the treatment of 15 anesthetized swine subjected to hypotension induced by standard hemorrhage, spinal cord injury, and sodium nitroprusside. From simulations and experimental responses it is found that the proposed automatic closed-loop control systems keeps mean arterial pressure near target.
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