Robust closed-loop control of propofol administration using WAVCNS index as the controlled variable

This paper presents a robust closed-loop strategy for control of depth of hypnosis. The proposed method regulates the electroencephalogram (EEG)-derived WAV_CNS index as a hypnosis measure by manipulating intravenous propofol administration. In contrast to many existing closed-loop methods, the control design presented in this paper produces stability and robustness against uncertainty by explicitly accounting for the pharmacokinetic (PK) and pharmacodynamic (PD) variability between different individuals, as well as unpredictable surgical stimuli that the closed-loop control is required to tolerate. This closed-loop control was evaluated using simulated surgical procedures in 44 patient models whose PK and PD were identified from real clinical data. The controller can deliver consistent and acceptable closed-loop induction and maintenance phase responses for patients with wide-ranging PK and PD differences.