A new paradigm for the closed-loop intraoperative administration of analgesics in humans.

We present a new paradigm for the closed-loop administration of analgesics during general anesthesia. The manipulated variable in the control system is the infusion rate of the opiate alfentanil, administered intravenously through a computer-controlled infusion pump (CCIP). The outputs to be controlled are the patient's mean arterial pressure (MAP) and the drug concentration in the plasma. Maintaining MAP within appropriate ranges provides optimal treatment of the patient's reactions to surgical stimuli. Maintaining plasma drug concentrations close to a reference value specified by the anesthesiologist allows to titrate analgesic administration to qualitative clinical end-points of insufficient analgesia. MAP is acquired invasively through a catheter cannula. Since plasma drug concentrations cannot be measured on-line, they are estimated via a pharmacokinetic model. We describe an explicit model-predictive controller which achieves the above-mentioned objectives. An upper constraint on drug concentrations is maintained to avoid overdosing. Constraints on the MAP are introduced to trigger a prompt controller reaction during hypertensive and hypotensive periods. Measurement artifacts in the MAP signal are rejected to prevent harmful misbehavior of the controller. We discuss the results of the clinical validation of the controller on humans.