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.

Group of patients that will receive vitamin C (ascorbic acid 1,5 g mixed with 0,9 % solution of sodium chloride 100 ml every 12 hours for 4 days intravenously).

Group of patients that will receive placebo (0,9 % solution of sodium chloride 100 ml every 12 hours for 4 days intravenously).

Unconscious survivors will have first brain imaging on the 3rd day, if still unconscious, second imaging around the 10th day. Imaging results will be descriptive (normal or pathological with signs of global ischemic injury: generalised edema, reduced grey and white matter differentiation, obliteration of the sulci). Second image will be compared to the first.

Unconscious survivors will have first EEG on the 3rd day, if still unconscious, second imaging around the 10th day. EEG results will be descriptive (normal or pathological with background suppression with or without periods of bursts, with or without response to external stimulus and similar patterns). Second EEG will be compared to the first.

Left ventricular ejection fraction (first, last, best, worst), determined by ultrasound will be noted.

Clinical evaluation of heart failure according to Killip-Kimball classification will be performed (worst result).

The need for vasopressors and inotropes will be noted, along with the name of the substance, maximal dosage and duration.

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

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