Robust Constrained Drug Dosage Regulation of Acute Inflammation Response Under Disturbances

Mathematical modelling of the biological processes, diseases and organs are important for the model-based control of diseases. Due to unmodeled dynamics, unknown and external disturbances, the performance of controllers based on these models are degraded for the accurate control. Therefore, robust controllers are need especially for the applications on patients. Inflammation, the cause of many complex biological phenomena and diseases, is a nonlinear process that is difficult to control. In this paper, continuous-time sliding-mode controller has been designed for the control of acute inflammation response (AIR) and antibacterial drug infusion under external disturbances both for septic and aseptic cases. Sliding-mode controller (SMC) is mostly used to control nonlinear systems against external disturbances and parametric uncertainties. Beside the control signal generation, we propose constraints on the control signals based on the clinical experiences such that the applied control signal is suitable for the health and improves the performance of the controller. Due to the multiple equilibrium point on the behavior of the acute inflammation response, it is difficult to design such model-based controllers without input constraints. In the numerical applications, septic death case and aseptic death case with disturbances are controlled and acceptable performances are obtained for future clinical applications.