Feasibility and Safety of Delivering a Ketone Drink to Comatose Survivors of Out-of-hospital Cardiac Arrest

Study Overview
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Brief Summary
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Every year, efforts are made to resuscitate about 30,000 people when their hearts stop outside of the hospital environment ('out-of-hospital cardiac arrest'). Early damage to the brain due to 'oxygen starvation' (seemingly paradoxically) gets worse when blood flow is restored. Of the 6,350 survivors admitted to intensive care units, 46% die from brain damage, and half of those who survive suffer long-term brain damage. Apart from avoiding a high temperature, nothing has been found which can protect the brain or improve outcome. 'Ketones' are chemicals naturally produced in the body from fat during starvation. They act as an energy source, but also as regulators of metabolism, and appear to protect cells from damage when oxygen supplies are scarce, or when blood flow is restored. The investigators want to see whether a ketone drink will protect the brain after out-of-hospital cardiac arrest. The investigators will study 10 cardiac arrest patients, and participants will be given the ketone drink via a feeding tube (which is routinely passed into the stomach in such cases). The investigators shall check that the drink is absorbed, and measure the ketone levels in the blood. The investigators will also measure important aspects of blood chemistry (including pH and blood sugar) and collect data on brain (electrical recordings called 'EEG' and 'SSEP') and heart function (ultrasound scans or 'echocardiographs') - both of which it is hoped might improve - in order to demonstrate that this is possible if it is to be included in a subsequent large trial. The study will be scrutinised by world experts in the field, who have also helped design the study. If this pilot study is a success, the investigators will apply to a major grant body to fund an appropriately-powered randomised controlled trial to determine whether ketones improve neurological outcome and survival in these patients. Results will also allow similar studies to be planned in heart attack, stroke and traumatic brain injury.

Official Title
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Feasibility and Safety of Delivering a Ketone Drink to Comatose Survivors of Out-of-hospital Cardiac Arrest

Conditions
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Out-Of-Hospital Cardiac Arrest

Intervention / Treatment
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* Dietary Supplement: Ketone ester drink


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged 18 years or above Male or female Comatose survivors of out-of-hospital cardiac arrest, defined as return of spontaneous circulation for at least 5 minutes with a score of <8 on the Glasgow Coma Scale For admission to intensive care unit for full, active treatment Exclusion Criteria: Primary neurological or intracranial cause of cardiac arrest In-hospital cardiac arrest Inclusion in another trial at time of recruitment Over 4 hours from time of return of spontaneous circulation to enrollment

Ages Eligible for Study
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Minimum Age: 18 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: Other
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Study group<br>Ketone ester drink to be administered by nasogastric tube. Initial bolus dose of 25 ml on enrollment. After 1 hour, begin 47 hr infusion at 6 ml per hour. | Dietary Supplement: Ketone ester drink<br>* Ketone ester drink<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline arterial blood gas values for pH |  | 48 hours | 
| Change from baseline arterial blood gas value for bicarbonate (mmol/L), |  | 48 hours | 
| Change from baseline arterial blood gas value for base excess (mEq/L), |  | 48 hours | 
| Change from baseline arterial blood gas value for glucose (mmol/L) |  | 48 hours | 
| Change from baseline arterial blood gas value for lactate (mmol/L) |  | 48 hours | 
| Change from baseline biochemistry laboratory results (full biochemistry panel including lipids, non-esterified fatty acids and serum insulin as per study protocol) |  | 48 hours | 
| Change from baseline haematology laboratory results (full blood count and coagulation profile as per study protocol) |  | 48 hours | 
| Time from arrival of participant to ketone drink administration (hh:mm) |  | 24 hours | 
| Number of participants receiving full course of ketone drink | As defined in study protocol: 25ml bolus followed after 1 hour by 47 hour infusion at 6 ml per hour | 48 hours | 
| Change from baseline serum troponin (ng/ml) |  | 12 hours | 
| Change from baseline serum neuron specific enolase (ng/ml) |  | 48 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline level of plasma betahydroxybutyrate (mmol/L) |  | 48 hours | 
| Number of participants undergoing electroencephalogram as per protocol |  | 72 hours | 
| Number of participants undergoing somatosensory evokes potentials as per protocol |  | 72 hours | 
| Number of participants undergoing echocardiography as per protocol |  | 72 hours |