Simulated mid-ranging control of propofol and remifentanil using EEG-measured hypnotic depth of anesthesia

This paper suggests an extension of an existing, clinically evaluated, closed-loop drug delivery system for hypnotic depth control using propofol. The extension introduces closed-loop administration of the analgesic drug remifentanil, thus forming a multiple input-single output (MISO) control system. Remifentanil acts and is metabolized at a significantly faster time scale than propofol. Direct control of analgesia is hindered by the current absence of a reliable real-time nociception monitor. However, several hypnotic depth monitors respond to nociception. Sudden changes in the measured hypnotic depth are frequently caused by changes in noxious stimulation. The novelty of this work lies in increasing the disturbance rejection bandwidth of the control system for hypnotic depth by directing the high frequency content of its control error to a remifentanil controller. Such a mid-ranging control system was implemented and tuned based on 23 patient models obtained from a previous clinical study and its performance is demonstrated through a simulation study.