Modelling and closed-loop control of skeletal muscle relaxation during general anaesthesia using mivacurium

During general anaesthesia drugs are administered to provide hypnosis, ensure analgesia and skeletal muscle relaxation. In this manuscript the main components of a newly developed controller for skeletal muscle relaxation are described. Muscle relaxation is controlled by administration of neuromuscular blocking agents. The degree of relaxation is assessed by supramaximal stimulation of the ulnar nerve and measuring the electromyogram response of the adductor pollicis muscle. For closed-loop control purposes a physiologically based pharmacokinetic and pharmacodynamic model of the neuromuscular blocking agent mivacurium is derived. The model is used to design an observer based state feedback controller, which is validated in clinical trials. As presented, the controller was able to maintain a preselected degree of muscle relaxation with excellent precision.