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

Impact of Vitamin C on Biomarkers of Neurologic Injury in Patients With Return of Spontaneous Circulation After Out-of-Hospital Cardiac Arrest

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.

Inclusion Criteria:

- comatose survivors of out-of-hospital arrest

Exclusion Criteria:

• patients with trauma, asphyxia, drowning or electrocution as a cause of cardiac arrest
• history of oxalate nephropathy or nephrolithiasis, glucose-6-phosphate dehydrogenase deficiency, and hemochromatosis
• pregnancy