Somatosensory evoked potentials for closed-loop control of anaesthetic depth using propofol in the urethane-anaesthetized rat  A. Angel, R.H. Arnott, D.A. Linkens, C.H. Ting  British Journal of Anaesthesia  Volume 85, Issue 3, Pages 431-439 (September 2000) DOI: 10.1093/bja/85.3.431 Copyright © 2000 British Journal of Anaesthesia Terms and Conditions

Fig 1 The technique of inflection latency estimation. Two successive average evoked responses are shown by dotted lines. Upon these are superimposed solid lines to show the inflection models which were mathematically derived from the biological data. Dashed lines show the inflection model of the average after being shifted (θ, Δy) towards the template. It is the extent of this shift which provides the index for changing latency between averages. Reproduced from Angel et al.,27 with permission. British Journal of Anaesthesia 2000 85, 431-439DOI: (10.1093/bja/85.3.431) Copyright © 2000 British Journal of Anaesthesia Terms and Conditions

Fig 2 Block diagram to show the drug delivery control system. All system parameters (i.e. of the PI controller, level limiter and filter) are adjustable in real time. The infusion pump is driven by analogue voltage commands and has two ramp modes, mm h−1 and mm min−1, with a resolution of 1 ramp unit. An appropriate ramp mode is selected by the pump driver according to the calculated infusion rate. The drug delivery control system was encapsulated as an additional module to an electrophysiological data acquisition system developed in Sheffield.28 The overall system was implemented using the C++ language (Visual C++ v2.2, Microsoft, USA) based on the object-oriented programming technique, on personal computers running Windows 95. System operations were performed via a friendly graphic user interface with both hot keys and a mouse. Only the latency change was used as a feedback variable; however, other diagnostic components of the somatosensory evoked potential were also displayed. British Journal of Anaesthesia 2000 85, 431-439DOI: (10.1093/bja/85.3.431) Copyright © 2000 British Journal of Anaesthesia Terms and Conditions

Fig 3 Records of the latency changes which were recorded in two of the animals in the study. (a) Data taken from an animal exhibiting a large degree of spontaneous fluctuation in its responsiveness. The upper panel shows the raw data obtained by measurement of changing latency (grey dots), upon which is superimposed the smoothed values of latency change which were calculated on-line and which were used by the controller in regulating infusion rate. The rapid onset of the effect of propofol is apparent, as is the period of gradual recovery which followed the cessation of infusion. The period during which the controller was instructed to induce a 1 ms increase in the latency, compared with that measured in the control period, is indicated by the horizontal black bar. The lower panel shows the rate of infusion of propofol 10 mg ml−1 i.v. under closed-loop control. The mean rate of administration, over the whole of the controlled period, was 32 mg kg−1 h−1. (b) Similar data taken from an animal which exhibited less spontaneous fluctuation in its responsiveness to the stimulus. The narrower scattering in the grey dots, which represent the raw data, is evident. Again, the superimposed line shows the smoothed values for latency change which were used in regulating the infusion rate. The lower panel shows the rate of infusion of propofol during the experiment, which had a mean rate of 27.6 mg kg−1 h−1 in this animal. British Journal of Anaesthesia 2000 85, 431-439DOI: (10.1093/bja/85.3.431) Copyright © 2000 British Journal of Anaesthesia Terms and Conditions

Fig 4 Plots similar to those obtained from the two animals which are represented in Fig. 3. Of interest is the excursion from the latency change set-point which occurred approximately 40 min after the beginning of the infusion period (asterisk). The rapid response of the controller (lower panel) in acting to restore the set-point through an increased rate of infusion is shown. British Journal of Anaesthesia 2000 85, 431-439DOI: (10.1093/bja/85.3.431) Copyright © 2000 British Journal of Anaesthesia Terms and Conditions

Fig 5 Mean values of latency change which were recorded in our animals (n=5) are shown in the upper panel. The black curve represents the smoothed data, as in Figs 3 and 4, which are superimposed upon the raw mean values obtained every 6 s during the experiment (grey dots). The period of infusion of propofol is indicated by the vertical lines and the horizontal black bar. The lower panel shows the cusum plot constructed from these raw mean data. Periods in which measured values differed little from those at the start of the experiment are reflected in horizontal portions of the cusum plot. When values differed from this comparison level, these differences were cumulatively summed to yield a portion of the curve which shows an increased gradient. When propofol infusion was discontinued, the animals commenced gradual recovery such that the rate of change in the cumulatively summed differences declined. Thus, as the animals recovered, the gradient of the cusum plot gradually returns to horizontal. The stability of the increased latency that was induced by the controller is reflected in the unchanging gradient in the portion of the cusum plot corresponding to the period of propofol infusion. Note that the cusum plot has units of milliseconds, but these are not meaningful in this type of representation. British Journal of Anaesthesia 2000 85, 431-439DOI: (10.1093/bja/85.3.431) Copyright © 2000 British Journal of Anaesthesia Terms and Conditions