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The effect of neuromuscular blockade on EEG-based measures of awareness

Halder, S.; Juel, B. E.; Pope, K. J.; Hardy, A.; Willoughby, J. O.; Storm, J. F.

2025-07-15 anesthesia
10.1101/2025.07.11.25331259 medRxiv
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BackgroundBoth basic and clinical consciousness research aims to find objective measures that reliably distinguish conscious from unconscious brain states. Electroencephalogram (EEG) measures are widely used, although they may be contaminated by electrical signals from muscles. MethodsTo assess this source of error, we investigated the impact of neuromuscular blockade (NMB) on proposed measures of consciousness (spectral slope, Lempel-Ziv complexity (LZc), connectivity, alpha peak frequency, power in canonical EEG frequency bands) computed from spontaneous high-density EEG recorded from six healthy volunteers in three different conditions: (1) awake-unparalysed, (2) awake-paralysed caused by neuromuscular blocking agent (NMBA), and (3) sedated-paralysed (sedated with propofol, paralysed by NMBA, (un)consciousness non-confirmable). ResultsThe markers we investigated distinguished awake-unparalysed states from sedated-paralysed with close to perfect accuracy. Our analysis revealed a serious failure of all measures, except alpha power, to recognise awake-paralysed, without sedation, as an aware state. Errors ranged from 19% of awake-paralysed time segments predicted as unaware (using spectral slope) to 100% (using LZc). Using alpha power, only 1% of all awake-paralysed segments were misclassified. Critically, the awake-paralysed is the state that is important to detect in sedated-paralysed patients, to prevent the experience of accidental awareness during general anaesthesia (AAGA). ConclusionsThis study clearly demonstrates that many EEG-based measures fail to recognise awareness in awake-paralysed subjects, by using a unique high-density EEG data set. Alpha power was determined to be the most robust measure to detect AAGA, but this may not generalise to all types of general anaesthetic agents.

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