Impact of Vitamin C on Biomarkers of Neurologic Injury in Survivors of Cardiac Arrest

Summary

Out-of-hospital cardiac arrest (OHCA) is one of the leading cause of death in the world. In Slovenia approximately 25% of resuscitated patients survives to discharge from hospitals, usually with poorer functional status.

One of key pathophysiological process responsible for poorer functional status is global hypoxic-ischemic injury, which is two-stage. Primary stage occurs immediately after cardiac arrest due to cessation of blood flow. With return of spontaneous circulation a secondary injury occurs, of which the leading process is an imbalance between oxygen delivery and consumption. Reperfusion exposes ischemic tissue to oxygen, resulting in the formation of large amounts of highly reactive oxygen species (ROS) within minutes. ROS lead to oxidative stress, which causes extensive damage to cell structures and leads to cell death. Consequently, necrosis and apoptosis are responsible for organ dysfunction and functional outcome of these patients.

Such injury of neural tissue causes brain damage, which is ultimately responsible for poor neurological and thus functional outcome of OHCA survivors. The extent of brain damage can be determined in several ways: clinically by assessing quantitative and qualitative consciousness and the presence of involuntary movements in an unconscious patient, by assessing activity on electroencephalographic record, by imaging of the brain with computed tomography and magnetic resonance imaging, as well as by assessing levels of biological markers of brain injury. Of the latter, the S-100b protein and neuron-specific enolase have been shown to be suitable for such assessment.

Oxidative stress is counteracted by the body with endogenous antioxidants that balance excess free radicals and stabilize cellular function. Vitamin C (ascorbic acid) is the body's main antioxidant and is primarily consumed during oxidative stress. Large amounts of ROS rapidly depletes the body's vitamin C stores.

Humans cannot synthesise vitamin C and enteral uptake of vitamin C is limited by transporter saturation. On the other hand, parenteral (venous) dosing of vitamin C can achieve concentrations of vitamin C above physiological and thus produce a stronger antioxidant effect. The beneficial effect of parenteral dosing of vitamin C has been establish in several preclinical and clinical studies in patients with ischemic stroke and cardiac arrest.

The investigators hypothesize that there is a similarly beneficial effect of vitamin C in survivors of OHCA.

Conditions

• Heart Arrest, Out-Of-Hospital
• Biomarkers
• Oxidative Stress
• Neurological Injury

Interventions

DRUG

Vitamin C

Ascorbic acid 1,5 g intravenously every 12-hours for 4 consecutive days

DRUG

Placebo

0,9 % solution of sodium chloride 100 ml intravenously every 12-hours for 4 consecutive days

Sponsors & Collaborators

• University Medical Centre Maribor

  lead OTHER

Principal Investigators

• Andrej Markota, MD, PhD, Assist. Prof. · University Medical Centre Maribor

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2020-10-01

Primary Completion

2022-10-31

Completion

2022-12-31

Countries

• Slovenia

Study Locations