Study Synopsis

Background

A primary aim of anaesthesia is to prevent awareness of surgery¹, and ablation of the experience of surgery is the most secure way to prevent awareness with recall¹. While the incidence of awareness with recall is very rare (0.1-0.2%^2-4), a recent systematic review suggested that consciousness of intraoperative events may occur in approximately 37% of patients in experimental studies (as identified by the validated clinical procedure referred to as the isolated forearm test [IFT])¹. However, Sanders et al recently found that incidence of consciousness with experience of the external world (connected consciousness) occurred in 4.6% of the general population undergoing anaesthesia⁵. The incidence in patients <40 years old was 11%. These rates, while lower than predicted by prior studies, suggest that somewhere between 1:20 and 1:10 patients may be aware under anaesthesia.

The IFT has been used for more than 40 years to identify intraoperative anaesthesia awareness in patients administered a neuromuscular block while under anaesthesia for surgery. It is a way of probing consciousness during anaesthesia and surgery in real time and, as such, is not dependent on recall. The test preserves patients’ ability to communicate by moving to a command even if they have been paralyzed to facilitate intubation. In the IFT, induction of anaesthesia is followed by inflation of a cuff on the dominant arm before neuromuscular blockade (paralysis) is induced. The cuff prevents paralysis of the hand allowing the patient to communicate to an observer through predefined hand movements, typically following a command like: “Mrs. Jones, if you can hear me, squeeze my hand”. This is then followed by further more complex commands such as: “Mrs. Jones, if you have pain, squeeze my hand two times” – to ensure the patient is comfortable.

To achieve our goals, we propose a multi-center prospective cohort study of a series of commands surveying responsiveness following laryngoscopy and intubation. Clinical care will not be controlled and will be left to the responsible clinician. We will also collect routinely recorded clinical data to frame the observations about IFT responsiveness, and additionally use non-invasive high-density electroencephalography (EEG) to provide information about the neural signature of IFT awareness. Finally, we will collect data on patient reported confusion and objectively measured confusion, to test whether IFT responsiveness has any association with these outcomes.

Rationale and hypothesis

The aim of ConsCIOUS2 is to explore the cognitive state of the IFT responder, explore the long-term sequelae, and to use EEG to investigate possible neural signatures of IFT responsiveness.

Objectives

Primary outcome and endpoint

Identify the incidence of IFT responsiveness following intubation in 18-40 year-old patients.

Secondary outcomes and endpoints

1. Cognition of responders during episode of IFT responsiveness as assessed by a structured series of commands.
2. Association between intraoperative IFT responsiveness and patient reported confusion following emergence from anaesthesia.
3. Estimation of the duration of responsiveness following intubation.
4. EEG data to identify monitoring patterns that discriminate responders and non-responders.
5. Feasibility of administering the IFT following surgical incision and every 30 minutes throughout the operation.
6. Incidence of anaesthesia awareness with recall.
7. Patient satisfaction associated with IFT responsiveness.
8. Demographic factors/anaesthetic factors that predispose to IFT.

Study design

This is a prospective cohort study.

Study population

This is an international multi-site study. We will collect data from 50-70 patients at the ADHB, with a total of about 600 patients worldwide. The collection of data from 50 patients at Waikato Hospital is about to get underway.

It is a priority for us to run the study in a manner that minimises its impact on clinical practice. The largest impediment is likely to be the requirement for 20 or so minutes to apply the electrode net.

We will consult the elective lists for eligible patients coming in from ORDA, ignoring the patients being seen first. After consulting the anaesthetist, we will approach the patient with information on the study. When he/she had time to consider participation, we will return to seek consent. After obtaining consent, we will apply the cap in a consultation room in ORDA. The cap may also be applied in the back area of recovery.

Patient notes will be amended to reflect our approach and consent of the patient.

Inclusion criteria

1. Age 18-40 years old.
2. Able to communicate in English.
3. Informed consent obtained.
4. Only patients able to safely follow the IFT commands when awake and prior to their operation.
5. Patients clinically requiring general anaesthesia, muscle relaxant, and intubation.

Exclusion criteria

1. Patients who are known to be pregnant.
2. Patients who are prisoners.
3. Anaesthetist and/or surgeon do not agree to the patient’s participation.
4. The patient has been or is to be consented for another study.
5. Operating theatre for procedure is not large enough to accommodate extra machinery.
6. Patient is undergoing rapid induction.

References

1. Sanders RD, Tononi G, Laureys S, Sleigh JW. Unresponsiveness ≠ Unconsciousness. Anesthesiology. 2012;116:946-959.
2. Ghoneim MM. Incidence of and risk factors for awareness during anaesthesia. Best Pract Res Clin Anaesthesiol. 2007;21(3):327-343.
3. Ghoneim MM, Block RI, Haffarnan M, Mathews MJ. Awareness during anesthesia: risk factors, causes and sequelae: a review of reported cases in the literature. Anesth Analg. 2009;108(2):527-535.
4. Sebel PS, Bowdle TA, Ghoneim MM, et al. The incidence of awareness during anesthesia: a multicenter United States study. Anesth Analg. 2004;99(3):833-839.
5. Sanders RD, Gaskell A, Raz A, et al. Incidence of Connected Consciousness after Tracheal Intubation: A Prospective, International, Multicenter Cohort Study of the Isolated Forearm Technique. Anesthesiology. 2017;126(2):214-222.

Method

The intervention portion of this study is the assignment to undergo IFT testing.

1. Eligibility will be reviewed, and informed consent gained.
2. Patient will be asked to rate their pain and anxiety on a scale from 1-10.
3. The EEG cap will be applied in pre-op, this takes roughly 10 minutes.

4. In theatre, the EEG machine (64-channel EGI/Philips 400 series) will be located outside of the sterile field, near the head of the patient. The cap is attached to the machine via a reticulated metal arm.
5. When the patient is positioned on the operating table, the EEG cap will be reconnected to the EEG machine, and the fidelity of the connection will be rechecked. This is anticipated to take less than 10 minutes.
6. After the standard preparation for anaesthesia and surgery, including standard monitoring and placement of an intravenous cannula for administration of medications, the arm without the intravenous cannula will have an additional blood pressure cuff placed around the forearm.
7. There are four different command sequences for the IFT and memory tasks, patients will be randomised to receive one of these.
8. After induction of anaesthesia as per standard procedures of the clinical team, but before administration of neuromuscular blockade (paralysis) the forearm without the cannula will be isolated by inflation of a blood pressure cuff to 50 mmHg above systolic pressure.
9. Immediately prior to intubation the patient will be given pre-intubation commands starting with “[NAME], squeeze my hand”. These commands take less than 30 seconds. The anaesthetist will be informed of the result and may choose to respond accordingly.
10. The patient will undergo laryngoscopy and intubation as per normal practice.
11. Within 10 seconds of the endotracheal tube passing through the cords, the post-intubation commands will be given. These commands take less than 2 minutes.
12. A clinical neuromuscular blockade monitor will be used to confirm lack of paralysis of the hand after the commands have been given and before the cuff is deflated. After 20 minutes the cuff will then be deflated. Clinical care will continue as normal. If the patient responds, the anaesthetist will then use their judgment as to whether to deepen the anaesthetic.
13. If the hand is accessible at the time of skin incision, the pre-intubation IFT commands will be repeated. If repeat neuromuscular blocker administration is required, the cuff will be re-inflated prior to administration. If commands are asked during the 20-minute window until cuff deflation, a clinical neuromuscular blockade monitor will be used to confirm lack of paralysis of the hand.
14. If the hand is accessible at 30 minute intervals during the case and upon emergence, the pre-intubation IFT commands will be repeated. If repeat neuromuscular blocker administration is required, the cuff will be re-inflated prior to administration. If commands are asked during the 20-minute window until cuff deflation, a clinical neuromuscular blockade monitor will be used to confirm lack of paralysis of the hand.
15. A data collection form will be completed by the study team.
16. 15 minutes and 60 minutes after admission to the PACU, the patient will undergo testing for confusion (RASS score, inattention test, Nu-DESC), and the patient will be asked to rate their pain and anxiety. Either of these may take place in the transition lounge. Administration should take less than 5 minutes.
17. The word retrieval task will occur 60 minutes after arrival in the PACU.
18. Following discharge from the recovery room, a satisfaction questionnaire and modified Brice questionnaire will be conducted within 24 hours and at 7 days postoperatively, and the answers recorded.