The mortality and neurological outcomes among out-of-hospital cardiac arrest survivors have not improved despite the medical advances. The whole body ischemia/reperfusion injuries after cardiac arrest mainly damaged the brain. To improve the neurologic outcome among those patients, additional interventions would be warranted. The investigators hypothesize that the combined use of cortisol, ascorbic acid (vitamin C), and thiamine during the early post-resuscitation period would attenuate the whole-body ischemia/reperfusion injuries among the out-of-hospital cardiac arrest survivors treated with targeted temperature management.
The mortality and neurological outcomes among the out-of-hospital cardiac arrest survivors are still dismal. In addition, the metabolic and oxidative stress can persist or even worsen at the cellular level after resuscitation, and these whole-body ischemia/reperfusion injuries contribute to multiple organ failure, known as the post-cardiac arrest syndrome. Therefore, additional interventions to reduces the injuries would be warranted. Cortisol has beneficial antioxidant and anti-apoptotic properties and stabilizes cellular membranes exposed to oxidative stress. It also maintains hemodynamic stability and improves organ function by reducing ischemia/reperfusion injuries. Thiamine is a cofactor that acts on enzymes essential for glucose metabolism, the generation of adenosine triphosphate, and nicotinamide adenine dinucleotide phosphate production. It assists the cellular metabolisms and attenuates the potential adverse effect of ascorbic acid (vitamin C) by preventing the conversion of ascorbic acid into oxalate. Ascorbic acid is a well-known antioxidant and has anti-inflammatory effects. It acted as an antioxidant defense substance, reducing reactive oxygen species and reactive nitrogen species and improving microcirculation by limiting oxidative injury and endothelial barrier disruption. The theoretical and experimental studies suggested the concomitant use of cortisol, thiamine, and ascorbic acid might have potential treatment synergism for whole-body ischemia/reperfusion injuries after cardiac arrest. The investigators hypothesize that their combined use during the early post-resuscitation period will reduce the whole-body ischemia/reperfusion injuries, especially the brain, in out-of-hospital cardiac arrest survivors treated with targeted temperature management.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
160
The combined administration of 3 drugs will be mixed in a 50 mL 0.9% saline bag respectively and administered through intravenous infusion over 60 min every 12 h for 3 days. 1. Ascorbic acid (Ascorbic acid Inj \[500mg\]®): 50 mg/kg, maximum single dose 3 g, daily dose 6 g 2. Thiamine (Thiamine hcl inj \[50mg\]®): 200 mg 3. Cortisol (Cortisolu inj \[100mg\]®): 100mg (The main exposure was corticosteroid therapy, defined as the use of systemic corticosteroids. But if unavailable, it could be converted to hydrocortisone-equivalent doses (methylprednisolone 1:5, dexamethasone 1:25, prednisolone 1:4).)
An identical volume of 0.9% saline (150mL) administered through intravenous infusion over 60 min every 12 h for 3 days.
Asan Medical Center
Seoul, South Korea
the peak neuron-specific enolase level
Serum Neuron-Specific Enolase (NSE) level at 48 to 72 hours after resuscitation will measured by enzyme immunoassay, respectively. We will use the peak neuron-specific enolase level.
Time frame: 48 to 72 hours
the delta neuron-specific enolase (NSE) level
The delta NSE level is defined as the difference between NSE at 24 hours and the peak NSE between 48 and 72 hours after cardiac arrest.
Time frame: at 48, 72 hours
The delta Sequential Organ Failure Assessment (SOFA) score
The delta SOFA is defined as the difference between SOFA admission and SOFA at 72 hours after cardiac arrest. Death within 72 hours will be counted as the maximum SOFA score (24).
Time frame: at 24, 48, 72 hours
30-day Mortality
All-cause death within 30 days
Time frame: 30 days
Time to death
The time to death is defined as the duration of survival within 30 days. Survival after 30 days will be counted as 30.
Time frame: 30 days
In-hospital mortality
All-cause death during hospitalization
Time frame: 1 year
Intensive Care Unit (ICU) stay
1 year
Time frame: The total length of ICU stay will be determined from the date of ICU admission until the patient is discharged from the Intensive Care Unit or the date of death from any cause, assessed up to 1 year after the first day of admission.
7-day mortality
All-cause death within 7 days
Time frame: 7 days
90-day mortality
All-cause death within 90 days
Time frame: 90 days
180-day mortality
All-cause death within 180 days
Time frame: 180 days
Time to Awakening
Days to neurological recovery, defined as Glasgow Outcome Scale \> 13 from cardiac arrest
Time frame: 30 days
ICU free day
Days in general ward transferred from ICU within 14 days from admission
Time frame: 14 days
Hospital stay
The total hospitalization days
Time frame: 1 year
Neurological outcome assessed using Cerebral Performance Category score
Cerebral Performance Category (CPC) score is defined as follows: CPC 1, Good cerebral performance (normal life); CPC 2, Moderate cerebral disability (disability but independent); CPC 3, Severe cerebral disability (conscious but disabled and dependent); CPC 4, Coma or vegetative state (unconscious); CPC 5, Brain death.
Time frame: at 30, 90, 180 days
Neurological outcome assessed using the modified Rankin Scale
The modified Rankin Scale (mRS) is a commonly used scale for measuring the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability. The scale runs from 0-6, running from perfect health without symptoms to death. 0 - No symptoms. 1. \- No significant disability. Able to carry out all usual activities, despite some symptoms. 2. \- Slight disability. Able to look after own affairs without assistance, but unable to carry out all previous activities. 3. \- Moderate disability. Requires some help, but able to walk unassisted. 4. \- Moderately severe disability. Unable to attend to own bodily needs without assistance, and unable to walk unassisted. 5. \- Severe disability. Requires constant nursing care and attention, bedridden, incontinent. 6. \- Dead.
Time frame: at 30, 90, 180 days
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