Robust MISO Control of Propofol-Remifentanil Anesthesia Guided by the NeuroSENSE Monitor

This paper describes the design and evaluation of a controller for multi-input single-output (MISO) propofol-remifentanil anesthesia, guided by feedback from a measure of depth-of-hypnosis (DOH). DOH monitors are commonly used in clinical practice to guide anesthetic dosing, however, there is currently no widely accepted nociception monitor to guide remifentanil (analgesic) infusion. Variability in the DOH measure has been associated with insufficient analgesia, and feasibility of closed-loop control of both propofol and remifentanil infusion using DOH feedback has been demonstrated. However, DOH variability does not provide a measure of analgesia in the absence of stimulation. Consequently, control of the opioid-hypnotic balance is lost in control systems relying on DOH feedback alone. The proposed design overcomes this limitation by introducing a second, indirect control objective. This paper defines clinical design specifications to achieve adequate anesthesia in a wide range of clinical cases, proposes a modification of the habituating control framework, and presents methods to translate the clinical objectives into control objectives within this framework. The developed design methodology provides a controller that: 1) meets the clinical objectives; 2) is robust to interpatient variability, both in single-input single-output and MISO operation; 3) is robust to nonlinear drug interactions; 4) gives the user control of the opioid-hypnotic balance in the absence of stimulation and in the presence of input saturation; and 5) improves disturbance rejection following nociceptive stimulation. The MISO system performed as designed in 80 clinical cases.