Assessing Covert Consciousness in Unresponsive Patients

Study Overview
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Brief Summary
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In this study, the investigators explore anesthesia as a tool for providing further insight into the level of consciousness of individuals with a clinical diagnosis of unresponsive wakefulness syndrome (UWS), but who possess some neurophysiological signatures of conscious awareness. This group, who could potentially be conscious, will herein be referred to as the target population. Our goal is to assess whether or not neurological patterns of consciousness in the target population respond to anesthesia in a similar manner to neurologically compromised individuals with known consciousness (e.g. those in minimally conscious state (MCS). In healthy controls, propofol-induced unconsciousness results in an elimination of the mismatch negativity event-related brain potential (ERP) and a diminished directed connectivity. The investigators hypothesize that at doses well below those required for surgery, anesthesia will have similar effects on these neural patterns in neurologically compromised patients with the potential for conscious awareness, but will not affect these patterns in those who lack consciousness.

Official Title
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Assessing the Potential for 'Covert Consciousness' in Unresponsive Patients

Conditions
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Consciousness Disorders

Intervention / Treatment
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* Device: EEG recording
* Drug: Anesthetics, Intravenous


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients admitted to the intensive care unit at Hamilton General Hospital who: Clinical status consistent with UWS (no responsiveness to commands) Clinical status consistent with MCS (minimal response to at least one command) Presence of an endotracheal tube (ETT) or a tracheostomy tube Between 18 and 50 years of age Exclusion Criteria: • Elevated intracranial pressure (ICP) Hepatic or renal failure Hemodynamic instability Active vasopressor therapy Previous open-head injury Previous intracranial pathology requiring neurosurgical interventions in the past 72 hours Anticipated ICU stay < 24 hours Documented allergy to propofol Pregnancy BMI > 35 kg/m2 Anyone who is deemed medically unsuitable for this study by the attending intensivist Patients who are already in a medically-induced coma for intracranial hypertension or status epilepticus

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Control 1 (negative control)<br>Individuals with a diagnosis of UWS without neural markers of consciousness | Device: EEG recording<br>* EEG recording with anesthetic (DIPRIVAN)<br>|
| Active Comparator: Control 2 (positive control)<br>Individuals with a diagnosis of MCS, who are behaviourally responsive and who present neural markers of consciousness | Device: EEG recording<br>* EEG recording with anesthetic (DIPRIVAN)<br>|
| Experimental: Target Population<br>Individuals with a clinical diagnosis of UWS, but who possess some neurophysiological signatures of conscious awareness | Device: EEG recording<br>* EEG recording with anesthetic (DIPRIVAN)<br>Drug: Anesthetics, Intravenous<br>* The participant will receive an intravenous infusion of propofol (DIPRIVAN Injectable Emulsion USP 1%, AstraZeneca).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Asymmetry in feedback vs. feedforward network connectivity | EEG networks will be monitored pre, during and post anesthesia. Directed connectivity will be calculated using phase lag index (PLI) and symbolic transfer entropy (STE) between all combinations of EEG sensors. Average values of feedback connectivity (e.g. from the frontal regions to parietal and occipital regions) will be compared to average values of feedforward connectivity (e.g. from parietal and occipital regions to frontal regions). Positive asymmetry will be correlated to the presence of conscious awareness and negative asymmetry will be correlated to the absence of conscious awareness. | 3 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Presence of P300 and N400 event-related potentials | EEG signals will be processed to extract the event-related EEG reactions to the auditory stimulation paradigm. Signals will be average 300 ms post-stimuli and 400 ms post-stimuli to assess the presence of the P300 and N400 event-related potentials. Presence of these event-related potentials will be correlated to the presence of conscious awareness and absence of these event-related potentials will be correlated to the absence of conscious awareness. | 3 hours |