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

Both 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.

To 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).

The 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).

This 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. Competing Interest Statement The authors have declared no competing interest. Funding Statement This analysis was funded by three grants awarded to JFS: ConsciousBrainConcepts project under the Life Science Convergence Projects initiative of the University of Oslo, the European Union Horizon 2020 Framework Programme for Research and Innovation under the Specific Grant Agreements No. 945539 (Human Brain Project SGA3), No. 785907 (Human Brain Project SGA2; JFS, ASN, BEJ), and the Norwegian Research Council (NRC grant 262950/F20 and FRIPRO 335828). Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The study was approved by the Southern Adelaide Clinical Human Research Ethics Committee. Participants gave written, informed consent for the procedures. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Data Availability All data produced in the present study are available upon reasonable request to the authors pending approval by the original authors.