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Trial registered on ANZCTR


Registration number
ACTRN12617000533392
Ethics application status
Approved
Date submitted
1/06/2016
Date registered
12/04/2017
Date last updated
18/03/2019
Date data sharing statement initially provided
18/03/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
What brain waves indicate conscious response during anaesthesia?
Scientific title
Electroencephalographic markers of behavioural responsiveness during anaesthesia in adults undergoing airway surgery
Secondary ID [1] 288926 0
None
Universal Trial Number (UTN)
U1111-1181-5561
Trial acronym
EMBRACE (Electroencephaolgraphic Markers of Behavioural Responsiveness during Anaesthesia: Consciousness Explored)
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Anaesthesia
Awareness
298265 0
Condition category
Condition code
Anaesthesiology 298408 298408 0 0
Other anaesthesiology
Neurological 302252 302252 0 0
Studies of the normal brain and nervous system

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
Level of consciousness will be assessed using the behavioural response to the command ((patient name, if you can hear me, squeeze my hand)
The exposures will be slow intravenous induction of general anaesthesia, and then the steps involved in the airway surgery surgery itself, and then emergence from anaesthesia.
Behavioural responses will be checked at regular intervals throughout anaesthetic induction, surgery and emergence in conjunction with continuous multichannel EEG recording
Intervention code [1] 294390 0
Diagnosis / Prognosis
Comparator / control treatment
N/A
Control group
Uncontrolled

Outcomes
Primary outcome [1] 297880 0
EEG markers. Corresponding multichannel EEG epochs will be analysed for spectral measures, connectivity measures, entropy and other putative markers of consciousness/unconsciousness
Timepoint [1] 297880 0
EEG recordings will be continuous from induction of anaesthesia to emergence from anaesthesia. Specific epochs of interest will include:
Loss of consciousness
Surgical stimulation
Episodes of spontaneous movement
Return of consciousness
Secondary outcome [1] 324413 0
Composite autonomic responses (heart rate variability (from continuous ECG recordings) and galvanic skin responses (continuous sensor))
Timepoint [1] 324413 0
Continuous monitoring from induction of anaesthesia to emergence from anaesthesia
Secondary outcome [2] 333542 0
Behavioural response to verbal command by an observer ('X (patient's name), if you can hear me, squeeze my hand') assessed by observer noting whether or not their hand was squeezed
Timepoint [2] 333542 0
Verbal commands will be given throughout the induction of anaesthesia (every 30 seconds), maintenance(every 5 minutes) and emergence of anaesthesia (every 30 seconds).
Secondary outcome [3] 333692 0
Reflex motor responses to painful stimuli
Timepoint [3] 333692 0
There will be continuous observation for movements which could occur following any painful stimulus; an observer will record the time and a description of any movements observed
Secondary outcome [4] 345364 0
Implicit memory of verbal cues given at time of insertion of operating laryngoscope measured using the 2 Alternative Forced Choice Method
Timepoint [4] 345364 0
In the post-anaesthesia care unit

Eligibility
Key inclusion criteria
Adults undergoing airway surgery at Waikato Hospital
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Inability to provide informed consent
Inability to follow commands appropriately preoperatively

Study design
Purpose
Natural history
Duration
Cross-sectional
Selection
Convenience sample
Timing
Prospective
Statistical methods / analysis
Analysis will be done using MATLAB software. We shall be testing temporal and spatial EEG changes across transitions of responsiveness. We shall be making within and between individual comparisons to determine the most sensitive and specific EEG markers of unresponsiveness.
The number of participants required was calculated using findings from a volunteer study to guide the required sample size to achieve 80% power with alpha type 1 error risk 0.05 for paired t-test comparisons of a EEG coherence measure across transitions of consciousness. We increased sample size over and above the minimum suggested by these calculations to account for a more heterogeneous study population and less tightly controlled anaesthetic regime

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment outside Australia
Country [1] 7769 0
New Zealand
State/province [1] 7769 0
Waikato

Funding & Sponsors
Funding source category [1] 293272 0
Hospital
Name [1] 293272 0
Waikato Hospital
Address [1] 293272 0
Selwyn Street and Pembroke Street, Waikato Hospital, Hamilton 3204
Country [1] 293272 0
New Zealand
Funding source category [2] 296100 0
Other
Name [2] 296100 0
Australian and New Zealand College of Anaesthetists
Address [2] 296100 0
630 St Kilda Rd., Melbourne VIC 3004, Australia
Country [2] 296100 0
Australia
Primary sponsor type
Hospital
Name
Waikato Hospital Dept of Anaesthesia
Address
Selwyn Street and Pembroke Street, Waikato Hospital, Hamilton 3204
Country
New Zealand
Secondary sponsor category [1] 294998 0
None
Name [1] 294998 0
Address [1] 294998 0
Country [1] 294998 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 294750 0
Southern Health and Disabilty Ethics Committee
Ethics committee address [1] 294750 0
Health and Disability Ethics Committees
Ministry of Health
Freyberg Building
20 Aitken Street
PO Box 5013
Wellington
6011
Ethics committee country [1] 294750 0
New Zealand
Date submitted for ethics approval [1] 294750 0
18/04/2016
Approval date [1] 294750 0
28/09/2016
Ethics approval number [1] 294750 0
16/STH/134

Summary
Brief summary
Aim
To evaluate electroencephalographic (EEG) markers of behavioural responsiveness during anaesthesia, providing insights into the mechanisms of loss and return of behavioural responsiveness during anaesthesia induction, noxious stimulation and emergence from anaesthesia

Significance
Awareness under anaesthesia is a rare but important complication of anaesthesia associated with significant negative psychological sequelae. The incidence of awareness with recall is well established at approximately 1 case per 1000 anaesthetic events. The ability of currently used depth of anaesthesia monitors to prevent awareness with recall is contentious, and whilst processed values correlate well with pharmacological levels or effect site concentrations of anaesthetic agents, their ability to detect behavioural responsiveness during anaesthesia as revealed by isolated forearm testing is poor. This is perhaps due to their reliance upon frontal EEG measurement and analysis.

Recent studies in healthy volunteers using functional magnetic resonance imaging (fMRI) and multichannel EEG have identified key changes in regions of the cortex associated with loss of behavioural responsiveness during anaesthesia. In particular there is growing evidence that a key marker of consciousness is the electroencephalographic connectivity between frontal and parietal regions of the brain.

Hypothesis
Loss of fronto-parietal connectivity as measured from the EEG results in loss of behavioural responsiveness to command during anaesthesia. Return of behavioural responsiveness during noxious stimulation or emergence from anaesthesia requires return of fronto-parietal connectivity.

Objectives
1. To evaluate multichannel EEG markers of behavioural responsiveness to command
2. To evaluate multichannel EEG markers of spontaneous motor response to noxious stimuli
3. To explore the relationships between cortical arousal and autonomic nervous system responses

Methods
Prospective observational cohort study of 60 patients undergoing microlaryngoscopy and airway surgery. Key features will be a slow controlled induction of anaesthesia to maintain spontaneous ventilation. Multichannel EEG and haemodynamic recordings will be taken continuously. Behavioural responsiveness will be checked by command at multiple time points during induction, emergence and during noxious stimuli. Spontaneous motor responses will also be recorded. The EEG recordings will be analysed using MATLAB software including spectral analysis, entropy and connectivity measures and relationships between EEG markers and behavioural responsiveness and non-responsiveness will be assessed using appropriate statistical tests.

Benefits
Ultimately we hope our findings will contribute to the development of improved depth of anaesthesia monitoring. We will obtain a rich dataset which can be further analysed to gain insights into mechanism of anaesthesia, interactions between hypnotic and analgesic agents and relationships between cortical arousals, EEG patterns and autonomic responses in the presence and absence of verbal and noxious stimuli.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 64934 0
Dr Amy Gaskell
Address 64934 0
Dept of Anaesthesia
Waikato Hospital
Private Bag 3200
Corner Pembroke Selwyn St
Hamilton
3204
Country 64934 0
New Zealand
Phone 64934 0
+64 78398899
Fax 64934 0
+64 7 8398761
Email 64934 0
amy.gaskell@waikatodhb.health.nz
Contact person for public queries
Name 64935 0
Dr Amy Gaskell
Address 64935 0
Dept of Anaesthesia
Waikato Hospital
Private Bag 3200
Corner Pembroke Selwyn St
Hamilton
3204
Country 64935 0
New Zealand
Phone 64935 0
+64 78398899
Fax 64935 0
+64 7 8398761
Email 64935 0
amy.gaskell@waikatodhb.health.nz
Contact person for scientific queries
Name 64936 0
Dr Amy Gaskell
Address 64936 0
Dept of Anaesthesia
Waikato Hospital
Private Bag 3200
Corner Pembroke Selwyn St
Hamilton
Country 64936 0
New Zealand
Phone 64936 0
+64 7 8398899
Fax 64936 0
+64 7 8398761
Email 64936 0
amy.gaskell@waikatodhb.health.nz

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
What supporting documents are/will be available?
Informed consent form
Ethical approval
Summary results
No Results