EEG-controlled closed-loop dosing of propofol in rats

Background. Based on previous pharmacokinetic and pharmacodynamicstudies, we have developed an EEG-controlled closed-loop systemfor the i.v. hypnotic agent propofol in rats. Methods. Seven adult male Sprague–Dawley rats (weight423–584 g) were included in the study. EEG was recordedwith occipito–occipital needle electrodes and the EEGpower spectrum was estimated. The median frequency (MEF) wasextracted from the power spectrum and was modified MEF (mMEF)to account for the occurrence of spikes and burst suppressionpatterns in the EEG. Propofol infusion was controlled by a model-basedadaptive control algorithm to maintain a set point of mMEF=3.0(SD 0.5) Hz. The performance of the feedback system was characterizedby the median performance error MDPE=median{(mMEF–setpoint)/set point} and the median absolute performance error(MDAPE). The effective therapeutic infusion (ETI) to maintainthe set point was determined from the resulting infusion rates. Results. In all rats a feedback period of 90 min could be performed.Mean MDPE was 1.2 (SE 0.4)% and MDAPE was 13.9 (0.3)%. The ETIwas 0.73 (SD 0.20) mg kg^–1 min^–1. Mean arterialpressure before propofol infusion was 148 (14) mm Hg, with thelowest value during closed-loop infusion being 110 (20) mm Hg. Conclusions. The feedback system presented here may be a usefultool not only for automatic drug control to maintain a definedhypnotic effect but may also be a powerful device in pharmacologicalstudies such as the determination of dose requirements or theassessment of drug–drug interactions. Br J Anaesth 2004; 92: 564–9