Feasibility of Closed-loop Titration of Propofol and Remifentanil Guided by the Spectral M-Entropy Monitor

Abstract

This randomized controlled trial describes automated coadministration of propofol and remifentanil, guided by M-Entropy analysis of the electroencephalogram. The authors tested the hypothesis that a novel dual-loop controller with an M-Entropy monitor increases time spent within predetermined target entropy ranges. Patients scheduled for elective surgery were randomly assigned in this single-blind study using a computer-generated list, to either dual-loop control using a proportional-integral-derivative controller or skilled manual control of propofol and remifentanil using target-controlled-infusion systems. In each group, propofol and remifentanil administration was titrated to a state entropy target of 50 and was subsequently targeted to values between 40 and 60. The primary outcome was the global score, which included the percentage of state entropy or response entropy in the range 40-60, the median absolute performance error and wobble. Data are presented as medians [interquartile range]. Thirty patients assigned to the dual-loop group and 31 assigned to the manual group completed the study. The dual-loop controller was able to provide induction and maintenance for all patients. The Global Score of State Entropy was better maintained with dual-loop than manual control (25 [19-53] vs. 44 [25-110], P = 0.043), and state entropy was more frequently maintained in the range of 40-60 (80 [60-85] vs. 60 [35-82]%, P = 0.046). Propofol (4.1 [2.9-4.9] vs. 4.5 [3.4-6.3] mg · kg(-1) · h(-1)) and remifentanil (0.18 [0.13-0.24] vs. 0.19 [0.15-0.26] μg · kg(-1) · min(-1)) consumptions and the incidence of somatic side effects were similar. Intraoperative automated control of hypnosis and analgesia guided by M-Entropy is clinically feasible and more precise than skilled manual control.