Design and Evaluation of a Closed-Loop Anesthesia System With Robust Control and Safety System

BACKGROUND:Closed-loop control of anesthesia involves continual adjustment of drug infusion rates according to measured clinical effect. The NeuroSENSE monitor provides an electroencephalographic measure of depth of hypnosis (wavelet-based anesthetic value for central nervous system monitoring [WAVCNS]). It has previously been used as feedback for closed-loop control of propofol, in a system designed using robust control engineering principles, which implements features specifically designed to ensure patient safety. Closed-loop control of a second drug, remifentanil, may be added to improve WAVCNS stability in the presence of variable surgical stimulation. The objective of this study was to design and evaluate the feasibility of a closed-loop system for robust control of propofol and remifentanil infusions using WAVCNS feedback, with an infusion safety system based on the known pharmacological characteristics of these 2 drugs. METHODS:With Health Canada authorization, research ethics board approval, and informed consent, American Society of Anesthesiologists I–III adults, requiring general anesthesia for elective surgery, were enrolled in a 2-phase study. In both phases, infusion of propofol was controlled in closed loop during induction and maintenance of anesthesia, using WAVCNS feedback, but bounded by upper- and lower-estimated effect-site concentration limits. In phase I, remifentanil was administered using an adjustable target-controlled infusion and a controller was designed based on the collected data. In phase II, remifentanil was automatically titrated to counteract rapid increases in WAVCNS. RESULTS:Data were analyzed for 127 patients, of median (range) age 64 (22–86) years, undergoing surgical procedures lasting 105 (9–348) minutes, with 52 participating in phase I and 75 in phase II. The overall control performance indicator, global score, was a median (interquartile range) 18.3 (14.2–27.7) in phase I and 14.6 (11.6–20.7) in phase II (median difference, −3.25; 95% confidence interval, −6.35 to −0.52). The WAVCNS was within ±10 of the setpoint for 84.3% (76.6–90.6) of the maintenance of anesthesia in phase I and 88.2% (83.1–93.4) in phase II (median difference, 3.7; 95% confidence interval, 0.1–6.9). The lower propofol safety bound was activated during 30 of 52 (58%) cases in phase I and 51 of 75 (68%) cases in phase II. CONCLUSIONS:Adding closed-loop control of remifentanil improved overall controller performance. This controller design offer