An integrated model of thermodynamic-hemodynamic-pharmacokinetic system and its application on decoupling control of intracranial temperature and pressure in brain hypothermia treatment.

Brain hypothermia treatment (BHT) is an intensive care characterized by simultaneous managements of various vital signs, such as intracranial temperature (ICT) and pressure (ICP), of the severe neuropatient. Medical treatments including therapeutic ambient cooling and diuresis are separately carried out based on the experience of the medical staff involved in the clinical management of various pathophysiological processes, such as thermodynamics, hemodynamics and pharmacokinetics. However, no special attention has been paid to the interactions among these subsystems in therapeutic hypothermia because of the lack of theoretical knowledge. Therefore, quantitative analyses using an integrated model of various physiological processes and their interactions are of pressing need. In the present paper, we propose a general compartmental model to describe the pathophysiological processes of the three aforementioned dynamics, on account of the dynamical analogy of temperature, pressure and concentration. The model is verified by the agreement of model-based simulation results with clinical evidence. Based on responses of the integrated model to various stimuli, a transfer function matrix is identified to linearly approximate the characteristic interrelationships between medical treatments (ambient cooling and diuresis) and the vital signs (ICT and ICP). Then a controller that decouples ambient cooling and diuresis is proposed for efficient management of ICT and ICP, enhancement of hypothermic decompression and reduction of diuretic dosage. Decoupling control simulation indicates that ICT and ICP of the integrated model, representing a patient under BHT, can be simultaneously regulated by a single PID controller for ambient cooling and another for diuresis. The proposed decoupler effectively establishes hypothermic decompression, reduces the dosage of diuretic and improves ICP management. Theoretical analyses of the integrated model and decoupling control of ICT and ICP provide insights into the intensive care of various pathophysiological processes in patients undergoing BHT.