Robust closed-loop control of hypnosis with propofol 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 WAVCNS index as measure of hypnosis by manipulating intravenous propofol administration. In contrast to many existing closed-loop control methods for hypnosis drug delivery, 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 individuals, as well as the unexpected surgical stimulation and anesthetic–analgesic interaction that the closed-loop control is required to tolerate. This robust closed-loop controller was evaluated in comparison with a heuristically tuned proportional-derivative-integral (PID) controller using a simulated surgical procedure on 44 patients whose PK and PD models were identified using real clinical data. The results demonstrate that the robust control strategy can deliver propofol to yield consistent and acceptable closed-loop induction and maintenance phase responses over wide-ranging PK and PD differences (mean rise and settling times of 4 min and 7 min and mean overshoot of less than 8%, which meets anesthesiologists’ response specifications), whereas its PID control counterpart exhibits limitations in performance.

► In this paper, we present a robust closed-loop strategy for control of depth of hypnosis. ► The proposed method regulates the electroencephalogram (EEG)-derived WAVCNS index as measure of hypnosis by manipulating intravenous propofol administration. ► A unique feature of the proposed controller is that it produces stability and robustness against the pharmacokinetic and pharmacodynamic variability between individuals and the unexpected surgical stimulation and anesthetic–analgesic interaction. ► The robust control strategy can deliver propofol to yield consistent and acceptable closed-loop induction and maintenance phase responses over wide-ranging PK and PD differences.