Incidence of Slow Delta EEG Frequencies (0.1-1 Hz) Before Burst Suppression: A Prospective Observational Pilot Study

1. BACKGROUND The anaesthetic drugs given to induce general anaesthesia act on the brain and produce characteristic changes in the electroencephalogram (EEG) signal recorded non-invasively from the frontal scalp area. In particular, oscillations in the delta (around 1 - 4 Hz) and alpha (8 -12 Hz) frequency bands are generally considered as markers of adequate anaesthesia dosing and hence unconsciousness, and disappear as the patient returns to consciousness. A further easily recognisable pattern in the EEG is where periods of high-amplitude bursts alternate with periods of low amplitude suppression (a nearly flat EEG signal) - so-called burst suppression. This pattern occurs at deep stages of general anaesthesia and is thought to represent a brain state response to excessive anaesthesia doses. Burst suppression occurs in around one third of all patients undergoing general anaesthesia, but can also reach much higher incidence rates such as 70% in older patients, and will depend largely on clinical dosing practice and cohort age.

In research led by a group from Harvard University, there have been claims that prior to the onset of burst suppression, slow wave activity in the EEG (which occurs at frequencies between 0.1 and 1 Hz) increases in amplitude (and in relationship to higher frequency oscillations), and that 'down states' in the slow EEG signal can act as indicators of upcoming burst suppression. Unfortunately, the two most commonly used commercial EEG anaesthesia devices used in Switzerland and worldwide, the Patient State Index (PSI by SedLine® Masimo) and the Bispectral Index™ (BIS™ by Medtronic), both remove these slower waveforms by high pass filtering so that they cannot be observed in the EEG signal visually on the monitor, and are absent in the EEG signal extracted for subsequent analysis.

It is currently not known how consistently the slow wave occurs during general anaesthesia, and if this waveform is consistently present prior to the onset of burst suppression, and if it can act as advance warning for impending burst suppression. This observational study will test the feasibility of measuring these slow frequency waveforms and examining their relationship to burst suppression.

For recording these slow waves between 0.1 and 1 Hz, that cannot be detected with a standard clinical anesthesia EEG monitor, the investigators plan to place an ULTEEMNite device (by CSEM Neuchâtel, Switzerland) immediately beside the electrodes strip of the commonly used Sedline EEG monitor on the foreheads of older patients undergoing general anaesthesia and to record the EEG signals from both devices simultaneously. The placement of the medically approved commercial Sedline device is standard clinical practice at the Cantonal Hospital of Aarau and the Hirslanden Clinic Aarau, and any clinically decision referring to titration of the depth of anesthesia will be made according to this device. The placement of the ULTEEMNite device will allow the investigators to record EEG signals that include the slow wave activity between 0.1 and 1 Hz. To note is that this study is independent from the ULTEEMNite device - the investigators do not wish to evaluate this device, but only use it as a recording device. The investigators are only interested in the information contained in slow wave activity between 0.1 and 1 Hz. 2. PROJECT OBJECTIVES AND DESIGN 2.1 Hypothesis and primary objective The hypothesis of this study is that EEG slow wave amplitudes and slow frequency spectral power will become maximal in the period immediately prior to the onset of burst suppression in the EEG recorded from the ULTEEMNite device. More specifically, power will be analysed in the EEG frequency spectra in the ranges from 0.1 to 1 Hz to confirm or disconfirm the presence of slow wave EEG activity. The investigators will use the clinically validated burst suppression algorithm of the Sedline monitor to provide a reproducible and objective measure of exact burst suppression onset.

2.2 Primary and secondary endpoints The primary variables of interest are peak amplitudes in the slow wave signal and absolute power in the EEG frequency spectra when recorded from immediately prior to the onset of burst suppression (as measured by the Sedline monitor).