This paper outlines the design of a fractional-order proportional–integral–derivative controller for regulating the induction phase of Propofol infusion in lean and obese patients. The obtained controller is implemented within the pharmacokinetic-pharmacodynamic model and the nonlinear Hill function to conduct closed-loop simulations. The latter are employed using a dataset comprising 24 patients to obtain clinical evaluation results. The design of the controller relies on a generic second-order plus dead time approximation model, which characterizes interpatient variability in response to Propofol infusion within the studied population. The fractional-order proportional–integral–derivative is tuned to achieve sufficient robustness margins ie phase margin, cutoff frequency, and the consideration of the iso-damping properties. The results show no undershoot and a smooth convergence to the desired value of the bispectral index, which indicates the depth of hypnosis.
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