Closed-Loop MISO Identification of Propofol Effect on Blood Pressure and Depth of Hypnosis

Abstract

Feasibility of closed-loop propofol anesthesia has been demonstrated in clinical trials; however, no closed-loop system is currently routinely used in clinical practice. Data from closed-loop clinical trials provide valuable information for system evaluation prior to market approval, including outlier behavior. To exploit this valuable data, closed-loop identification in the presence of nonzero disturbances is required. Disturbances due to stimulation are not zero mean and will cause bias in models identified from clinical data. In this paper, we use multiple-input single-output (MISO) closed-loop identification to take the response to disturbances during induction of anesthesia into account. It is shown that direct MISO output-error identification introduces limited bias for this specific closed-loop identification problem and the use of more complex closed-loop identification methods does not improve model accuracy. Using this approach, we identify and validate a set of models that describes both the blood pressure and the depth-of-hypnosis response to propofol infusion for patients at risk of cardiovascular suppression. Quantification of both these responses for the same patients provides a valuable basis for the design and evaluation of constrained control systems.