Modeling and closed-loop control of hypnosis by means of bispectral index (BIS) with isoflurane

A model-based closed-loop control system is presented to regulate hypnosis with the volatile anesthetic isoflurane. Hypnosis is assessed by means of t he bispectral index (BIS), a processed parameter derived from the electroen cephalogram. Isoflurane is administered through a closed-circuit respirator y system. The model for control was identified on a population of 20 health y volunteers. It consists of three parts: a model for the respiratory syste m, a pharmacokinetic model and a pharmacodynamic model to predict BIS at th e effect compartment. A cascaded internal model controller is employed. The master controller compares the actual BIS and the reference value set by t he anesthesiologist and provides expired isoflurane concentration reference s to the slave controller. The slave controller maneuvers the fresh gas ane sthetic concentration entering the respiratory system. The controller is de signed to adapt to different respiratory conditions. Anti-windup measures p rotect against performance degradation in the event of saturation of the in put signal. Fault detection schemes in the controller cope with BIS and exp ired concentration measurement artifacts. The results of clinical studies o n humans are presented.