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Accidental awareness during general anesthesia (AAGA) is defined as an unexpected awareness of the patient during general anesthesia. This phenomenon occurs in 1%-2% of high-risk practice patients and can cause physical suffering and psychological after-effects, called posttraumatic stress disorder. In fact, no monitoring techniques are satisfactory enough to effectively prevent AAGA; therefore, new alternatives are needed. Because the first reflex for a patient during an AAGA is to move, but cannot do so because of the neuromuscular blockers, we believe that it is possible to design a brain-computer interface (BCI) based on the detection of movement intention to warn the anesthetist. To do this, we propose to describe and detect the changes in terms of motor cortex oscillations during general anesthesia with propofol, while a median nerve stimulation is performed. We believe that our results could enable the design of a BCI based on median nerve stimulation, which could prevent AAGA.
To our knowledge, no published studies have investigated the detection of electroencephalographic (EEG) patterns in relation to peripheral nerve stimulation over the sensorimotor cortex during general anesthesia. The main objective of this study is to describe the changes in terms of event-related desynchronization and event-related synchronization modulations, in the EEG signal over the motor cortex during general anesthesia with propofol while a median nerve stimulation is performed.
STIM-MOTANA is an interventional and prospective study conducted with patients scheduled for surgery under general anesthesia, involving EEG measurements and median nerve stimulation at two different times: (1) when the patient is awake before surgery (2) and under general anesthesia. A total of 30 patients will receive surgery under complete intravenous anesthesia with a target-controlled infusion pump of propofol.
The changes in event-related desynchronization and event-related synchronization during median nerve stimulation according to the various propofol concentrations for 30 patients will be analyzed. In addition, we will apply 4 different offline machine learning algorithms to detect the median nerve stimulation at the cerebral level. Recruitment began in December 2022. Data collection is expected to conclude in June 2024.
STIM-MOTANA will be the first protocol to investigate median nerve stimulation cerebral motor effect during general anesthesia for the detection of intraoperative awareness. Based on strong practical and theoretical scientific reasoning from our previous studies, our innovative median nerve stimulation–based BCI would provide a way to detect intraoperative awareness during general anesthesia.
Clinicaltrials.gov NCT05272202; https://clinicaltrials.gov/ct2/show/NCT05272202
PRR1-10.2196/43870
Unexpectedly awakening during surgery is a terrifying experience for patients, who fear it, but also for the medical staff, who are worried that the situation may occur under their supervision [
The rate of AAGA in high-risk practices (eg, obstetric, cardiac, and thoracic) varies from 1% to2% [
The patients’ testimonies show that the first reaction during an AAGA is usually to move to alert the medical staff [
These preliminary results also showed that propofol sedation (at 0.5 µg/mL and 1 µg/mL) has no negative impact on the ability of an MNS-based BCI to detect MI. Concretely, at relatively low concentrations, ERD/ERS patterns are still present in the sensorimotor cortex [
The first objective of this study is to verify that ERD and ERS patterns induced by MNS can be detected in the cortical motor EEG signal under various concentrations of propofol corresponding to the anesthetic doses required for general anesthesia. The secondary objective is to characterize and understand how the ERD and ERS generated after each MNS will be altered according to each concentration of propofol at the effect site. These results will be discussed in relation to previous results obtained from a protocol investigating the effect of light propofol sedation on EEG signals in the motor cortex. The third objective is to analyze EEG signals offline and try to detect MNS under propofol with new machine learning algorithms. Complementary, the short and middle latency components of the somatosensory evoked potentials (SEPs) will be analyzed for different propofol concentrations. Finally, the long-term goal is to design a BCI that can detect intraoperative awareness during general anesthesia.
The study will be held in an approved location in the operating theaters, at the University Hospital of Bruxelles-Brugmann (Belgium). An anesthetic evaluation will be performed by the study investigator (DS) within 1 month prior to surgery. During this consultation, the study protocol will be explained to the patient, and the different explanatory documents will be given. Only eligible subjects will be enrolled (inclusion and exclusion criteria are listed). Participation is completely voluntary and withdrawal will be always possible at any time without affecting the level of care that will be received. There will be no financial compensation for this study. Each voluntary patient recruited for the study will benefit from the standard of care before, during, and after the surgery. On the day of surgery, and as recommended, the anesthetist will check that there are no current contraindications to perform general anesthesia (ie, failure to fast, fever, occurrence of other medical conditions or disease, unusual blood sample, etc).
Recording a patient's baseline EEG during MNS without an anesthetic drug administered is a prerequisite for the proper functioning of the BCI. It will take place before surgery in a specific quiet room in the postanesthesia care unit. The estimated time to set the EEG headset is 25 minutes, and the estimated time for baseline EEG monitoring is 20 minutes (see
Schedule of enrollment, interventions, and assessments.
Action | Anesthesia | Preanesthetic visit | Presurgical visit | During surgery |
Location | Consultation office | Hospital room | Specific room | Operation room |
Timeliness | (−50 days; −5 days) | (−1 day) | (d-day)b | (d-day) |
Consent collection | N/Aa | N/A | N/A | N/A |
Consent confirmation | N/A | N/A | ✓ | N/A |
Providing information documents | ✓ | N/A | N/A | N/A |
Checking inclusion and exclusion criteria | ✓ | N/A | ✓ | N/A |
Medical interview | ✓ | ✓ | ✓ | N/A |
Clinical examination | ✓ | ✓ | ✓ | ✓ |
Electroencephalographic recording | N/A | N/A | ✓ | ✓ |
Electromyography recording | N/A | N/A | N/A | ✓ |
Median nerve stimulation | N/A | N/A | ✓ | ✓ |
Adverse event collection | N/A | N/A | N/A | ✓ |
aN/A: not applicable.
bd-day: day of experimentation.
Considering the SEP stimulation, we consider that nonpainful stimuli will consist of square electrical pulses of 0.2 milliseconds of duration, generated by Micromed device Sd Ltm Stim Energy (Micromed) and delivered through a pair of grass gold cup electrodes (cathode [−] placed proximally) to the right/left median nerve at the wrist [
In this clinical protocol, a total of 30 patients who require scheduled surgery under general anesthesia will be enrolled. For the recruitment of this study, we have designed a flyer that will be disseminated through different media channels. Participation in this experiment will not be remunerated. Patients will be exposed to the same risks of general anesthesia limited to propofol. The doses used in this clinical protocol are the same as those that induce loss of consciousness during conventional surgery.
The inclusion criteria include patients (1) who have received full details of the research organization and have signed our informed consent, (2) aged between 18 and 81 years, (3) scheduled for surgery with the use of total intravenous sedation with propofol, and (4) who are affiliated to a social security regime in Belgium. We shall exclude patients who (1) are allergic to propofol or its ingredients, (2) have a history of an anaphylactic reaction during anesthesia, (3) are female due to the impossibility of checking pregnancy status, (4) are deprived of liberty by a judicial or administrative decision, (5) are under psychiatric care, (6) are unable to give consent and without being subjected to a legal protection measure, (7) refuse to participate in the study, (8) have a BMI below 20 or above 35 kg/m², (9) require surgery for less than an hour, (10) have a pathological history related to the right median nerve, and (11) have any drug addiction.
This research was officially approved by an ethical committee from Belgium (CHU Brugmann, CE 2021/225) and was registered at EUDRACT (2021-006457-56). The study protocol was also registered on ClinicalTrials.gov (NCT05272202). This protocol will follow the principles of the Declaration of Helsinki and the Medical Research Involving Human Subjects Act [
Motor EEG signals will be collected through the OpenViBE software platform with eego mylab system (ANT neuro) 64-EEG channels, covering the entire scalp at 16,000 Hz and 1 external channel placed on the dorsum of the contralateral hand to the electric stimulation, by means of an adhesive surface electrode. All offline analyses will be performed using the EEGLAB toolbox [
The data processing methods will be similar to those described in the MOTANA protocol [
In addition to the event-related spectral perturbation analyses, we will apply 4 different offline machine learning algorithms to detect the MNS at the cerebral level. To do this, these algorithms are based on 4 classification methods in a 4-fold cross-validation scheme. The classification score will be computed for the MNS versus the rest class. Each trial will be segmented into a motor task time window and a resting time window, both lasting 2 seconds. The motor task time window will begin 0.5 seconds after the MNS, and the resting phase time window will begin 3 seconds before the MNS. The first classification method is a linear discriminant analysis method using a common spatial pattern [
The duration of the participation is from 45 minutes before surgery (installation of the EEG cam and the median nerve stimulator) until the end of surgery.
The expected overall duration of the research, including the time required for the completion of the data analysis, is 4 years. The promoter (CHU Brugmann) reserves the right to stop the research (1) if serious, there are significant procedural deviations in the protocol that could impact the statistical analysis of the data, (2) if recruitment of subjects is not adequate, or (3) if a significant issue regarding the safety and rights of the subjects arises.
Data will be collected with a case report form and patient data will be anonymized (ie, a unique study number will be assigned to each individual). The case report form will contain demographic information of the patient, undesirable events which may be experienced during the study, the anesthesia chart will be photocopied at the end of the procedure and anonymized, and EEG data stored electronically under the supervision of the principal investigator.
A total of 30 patients will be involved in the STIM-MOTANA protocol. Patients, patient advisors, and the public were not involved in the development of the research questions or in the design of the study. Patient involvement in the study includes answering survey questionnaires at baseline and at each follow-up. Summaries of study results will be disseminated to study participants via email or mail. The results will be published in international peer-reviewed journals, and summaries will be provided to the funders and patients.
A total of 30 patients will be involved in the STIM-MOTANA protocol. We will compute the amplitude of ERD/ERS modulations before and after each MNS during the different phases of anesthesia at 2 different times: when the patient is awake before surgery and under general anesthesia. The primary evaluation end point will be the amplitude of the ERD. According to the Pfurtscheller method, ERD/ERS modulations will be calculated using a baseline taken before each stimulation [
In this project, we need to reach the highest MI EEG detection accuracies as possible, which is necessary in the context of a surgery for which we need a very high true positive rate (ideally all AAGAs are detected) as well as a very low false positive rate (ideally no false alarm). To do so, we will build BCI classifiers based on Riemannian geometry [
When the manuscript was initially submitted, recruitment had not started. The recruitment began in December 2022. The current protocol version is version 1 and was previously accepted by the ethical committee of the CHRU Brugmann Hospital.
STIM-MOTANA is an interventional study aimed at designing an innovative BCI-based EEG-motor brain activity, which would detect the intention to move of a patient during general anesthesia. STIM-MOTANA is the first study to investigate cerebral motor activity modulations following peripheral nerve stimulation during general anesthesia.
AAGA can occur unexpectedly and is therefore a complication that cannot be easily anticipated and that is only retrospectively diagnosed. The STIM-MOTANA protocol proposes to detect intraoperative awareness reliably by analyzing, in real-time, brain motor activity under general anesthesia with a BCI based on MNS and new machine learning methods. Designing such a BCI presents us with 2 challenges. The first one is to detect the MI of a person who is a victim of AAGA without any time marker presented to the subject (ie, asynchronously) since, during AAGA, it is impossible to ask and know exactly when the patient will intend to move. Unfortunately, the literature clearly shows insufficient classification accuracies and high false positive rates with asynchronous BCI [
STIM-MOTANA will provide the first protocol study to investigate MNS cerebral motor effect during general anesthesia for the detection of intraoperative awareness. Based on strong practical and theoretical scientific reasoning from our previous studies, an innovative MNS-based BCI used in this study would provide a way to detect intraoperative awareness during general anesthesia.
Peer review report by Fonds de la Recherche Scientifique (FNRS) / National Funds of Research of Belgium - SVS-3 Sciences de la Vie et de la Santé - 3 (Brussels, Belgium).
accidental awareness during general anesthesia
brain-computer interface
electroencephalography
event-related desynchronization
event-related synchronization
movement intention
median nerve stimulation
somatosensory evoked potential
target-controlled infusion
This work was supported by the Brugmann Foundation (Belgium) and the National Funds of Research of Belgium (Belgium). The Brugmann Foundation supported the purchase of the equipment for the electroencephalographic acquisition. The National Funds of Research of Belgium offered a grant for a research fellow (SR) to carry out the experiments and analyses.
The datasets generated and analyzed during the current study will be available from the corresponding author on request. Records of all patients will be kept separately in a secure place in the CHU-Brugmann.
SR conceived the idea and rationale for this study. DS and PG are the principal investigators of this study. SR, JL, DS, CM, AMCA, GC, and PG contributed to the design and protocol of this study, and are responsible for the collection and analysis of the data. SR, JL, DS, CM, AMCA, SJB, GC, and PG were responsible for drafting and critically revising the manuscript. All authors have read and approved the final version of this manuscript.
None declared.