Closed-loop control of analgesia in humans

Abstract

We designed a feedback controller for the automatic delivery of analgesics drugs during surgery. The manipulated variable in the control system is the infusion rate of the opiate alfentanil, administered intravenously through a computer controlled infusion pump. The controller regulates two outputs: the patient's mean arterial pressure (MAP) and the drug concentrations in the plasma. Maintaining MAP within acceptable physiological ranges minimizes the patient's stress response to surgical stimulation. Tracking plasma concentrations offers the possibility of titrating analgesic drugs to alternative, qualitative signs of inadequate analgesia. Since analgesic drug concentrations can not be measured on-line, a pharmacokinetic model is used to predict the second output of the control system. An explicit model predictive controller was designed and implemented in our real-time platform. Artifact tolerant control schemes were introduced to prevent the system from harmful behaviour in the presence of MAP artifacts. The closed-loop controller was tested during surgical procedures in humans. The results are presented and discussed.