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BJA Advance Access originally published online on February 20, 2004
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British Journal of Anaesthesia, 2004, Vol. 92, No. 4 564-569
© 2004 The Board of Management and Trustees of the British Journal of Anaesthesia

Review Article

EEG-controlled closed-loop dosing of propofol in rats

A. Tzabazis, H. Ihmsen*, M. Schywalsky and H. Schwilden

Klinik für Anästhesiologie, Universität Erlangen-Nürnberg, Krankenhausstrasse 12,D-91054 Erlangen, Germany

*Corresponding author. E-mail: Harald.Ihmsen@kfa.imed.uni-erlangen.de

Background. Based on previous pharmacokinetic and pharmacodynamic studies, we have developed an EEG-controlled closed-loop system for the i.v. hypnotic agent propofol in rats.

Methods. Seven adult male Sprague–Dawley rats (weight 423–584 g) were included in the study. EEG was recorded with occipito–occipital needle electrodes and the EEG power spectrum was estimated. The median frequency (MEF) was extracted from the power spectrum and was modified MEF (mMEF) to account for the occurrence of spikes and burst suppression patterns in the EEG. Propofol infusion was controlled by a model-based adaptive control algorithm to maintain a set point of mMEF=3.0 (SD 0.5) Hz. The performance of the feedback system was characterized by the median performance error MDPE=median{(mMEF–set point)/set point} and the median absolute performance error (MDAPE). The effective therapeutic infusion (ETI) to maintain the 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 ETI was 0.73 (SD 0.20) mg kg–1 min–1. Mean arterial pressure before propofol infusion was 148 (14) mm Hg, with the lowest value during closed-loop infusion being 110 (20) mm Hg.

Conclusions. The feedback system presented here may be a useful tool not only for automatic drug control to maintain a defined hypnotic effect but may also be a powerful device in pharmacological studies such as the determination of dose requirements or the assessment of drug–drug interactions.

Br J Anaesth 2004; 92: 564–9


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