ANZCTR - Registration

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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

7/09/2021

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]

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

Condition category

Condition code

Anaesthesiology

Other anaesthesiology

Neurological

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]

Diagnosis / Prognosis

Comparator / control treatment

N/A

Control group

Uncontrolled

Outcomes

Primary outcome [1]

EEG markers. Corresponding multichannel EEG epochs will be analysed for spectral measures, connectivity measures, entropy and other putative markers of consciousness/unconsciousness

Timepoint [1]

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]

Composite autonomic responses (heart rate variability (from continuous ECG recordings) and galvanic skin responses (continuous sensor))

Timepoint [1]

Continuous monitoring from induction of anaesthesia to emergence from anaesthesia

Secondary outcome [2]

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]

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]

Reflex motor responses to painful stimuli

Timepoint [3]

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]

Implicit memory of verbal cues given at time of insertion of operating laryngoscope measured using the 2 Alternative Forced Choice Method

Timepoint [4]

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

Sex

Both males and females

Can healthy volunteers participate?

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

4/06/2018

Actual

31/10/2018

Date of last participant enrolment

Anticipated

25/04/2022

Actual

Date of last data collection

Anticipated

Actual

Sample size

Target

Accrual to date

Final

Recruitment outside Australia

Country [1]

New Zealand

State/province [1]

Waikato

Funding & Sponsors

Funding source category [1]

Hospital

Name [1]

Waikato Hospital

Address [1]

Selwyn Street and Pembroke Street, Waikato Hospital, Hamilton 3204

Country [1]

New Zealand

Funding source category [2]

Other

Name [2]

Australian and New Zealand College of Anaesthetists

Address [2]

630 St Kilda Rd., Melbourne VIC 3004, Australia

Country [2]

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]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Southern Health and Disabilty Ethics Committee

Ethics committee address [1]

Health and Disability Ethics Committees
Ministry of Health
Freyberg Building
20 Aitken Street
PO Box 5013
Wellington
6011

Ethics committee country [1]

New Zealand

Date submitted for ethics approval [1]

18/04/2016

Approval date [1]

28/09/2016

Ethics approval number [1]

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

Dr Amy Gaskell

Address

Dept of Anaesthesia
Waikato Hospital
Private Bag 3200
Corner Pembroke Selwyn St
Hamilton
3204

Country

New Zealand

Phone

+64 78398899

Fax

+64 7 8398761

amy.gaskell@waikatodhb.health.nz

Contact person for public queries

Name

Amy Gaskell

Address

Dept of Anaesthesia
Waikato Hospital
Private Bag 3200
Corner Pembroke Selwyn St
Hamilton
3204

Country

New Zealand

Phone

+64 78398899

Fax

+64 7 8398761

amy.gaskell@waikatodhb.health.nz

Contact person for scientific queries

Name

Amy Gaskell

Address

Dept of Anaesthesia
Waikato Hospital
Private Bag 3200
Corner Pembroke Selwyn St
Hamilton

Country

New Zealand

Phone

+64 7 8398899

Fax

+64 7 8398761

amy.gaskell@waikatodhb.health.nz

Data sharing statement

Will individual participant data (IPD) for this trial be available (including data dictionaries)?

No/undecided IPD sharing reason/comment

What supporting documents are/will be available?

No Supporting Document Provided

Results publications and other study-related documents

Documents added manually

No documents have been uploaded by study researchers.

Documents added automatically

No additional documents have been identified.

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