{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:55:15Z","timestamp":1787028915993,"version":"build-2736575974"},"reference-count":58,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2024,1,5]],"date-time":"2024-01-05T00:00:00Z","timestamp":1704412800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100016224","name":"Internal Research Projects Grant of University Medical Centre Maribor, Slovenia","doi-asserted-by":"publisher","award":["IRP-2019\/02-05"],"award-info":[{"award-number":["IRP-2019\/02-05"]}],"id":[{"id":"10.13039\/501100016224","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Background and Objectives: Survival with favorable neurologic outcomes after out-of-hospital cardiac arrest (OHCA) remains elusive. Post-cardiac arrest syndrome (PCAS) involves myocardial and neurological injury, ischemia-reperfusion response, and underlying pathology. Neurologic injury is a crucial determinant of survival and functional outcomes, with damage caused by free radicals among the responsible mechanisms. This study explores the feasibility of adding intravenous vitamin C to the treatment of OHCA survivors, aiming to mitigate PCAS. Vitamin C, a nutrient with antioxidative and free radical-scavenging properties, is often depleted in critically ill patients. Materials and Methods: This randomized, double-blinded trial was conducted at a tertiary-level university hospital with adult OHCA survivors. Participants received either standard care or the addition of 1.5 g of intravenous vitamin C every 12 h for eight consecutive doses. Neurologic injury was assessed using neuron-specific enolase (NSE) levels, with additional clinical and laboratory outcomes, such as enhanced neuroprognostication factors, inflammatory markers, and cardiac parameters. Results: NSE levels were non-significantly higher in patients who received vitamin C compared to the placebo group (55.05 \u00b5g\/L [95% confidence interval (CI) 26.7\u2013124.0] vs. 39.4 \u00b5g\/L [95% CI 22.6\u201361.9], p &gt; 0.05). Similarly, a non-significantly greater proportion of patients in the vitamin C group developed myoclonus in the first 72 h. We also observed a non-significantly shorter duration of mechanical ventilation, fewer arrhythmias, and reduced length of stay in the intensive care unit in the group of patients who received vitamin C (p = 0.031). However, caution is warranted in interpretation of our results due to the small number of participants. Conclusions: Our findings suggest that intravenous vitamin C should not be used outside of clinical trials for OHCA survivors. Due to the small sample size and conflicting results, further research is needed to determine the potential role of vitamin C in post-cardiac arrest care.<\/jats:p>","DOI":"10.3390\/medicina60010103","type":"journal-article","created":{"date-parts":[[2024,1,5]],"date-time":"2024-01-05T05:12:17Z","timestamp":1704431537000},"page":"103","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Addition of Vitamin C Does Not Decrease Neuron-Specific Enolase Levels in Adult Survivors of Cardiac Arrest\u2014Results of a Randomized Trial"],"prefix":"10.3390","volume":"60","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-6105-143X","authenticated-orcid":false,"given":"Matev\u017e","family":"Priv\u0161ek","sequence":"first","affiliation":[{"name":"Emergency Medical Services, Healthcare Centre Dr. Adolf Drolc, Cesta Proletarskih Brigad 21, 2000 Maribor, Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matej","family":"Strnad","sequence":"additional","affiliation":[{"name":"Emergency Medical Services, Healthcare Centre Dr. Adolf Drolc, Cesta Proletarskih Brigad 21, 2000 Maribor, Slovenia"},{"name":"Emergency Department, University Medical Centre Maribor, Ljubljanska Ulica 5, 2000 Maribor, Slovenia"},{"name":"Department of Emergency Medicine, Faculty of Medicine, University of Maribor, Taborska Ulica 8, 2000 Maribor, Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrej","family":"Markota","sequence":"additional","affiliation":[{"name":"Department of Medical Intensive Care, Clinic of Internal Medicine, University Medical Centre Maribor, 2000 Maribor, Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,1,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.resuscitation.2021.02.007","article-title":"European Resuscitation Council Guidelines 2021: Epidemiology of cardiac arrest in Europe","volume":"161","author":"Grasner","year":"2021","journal-title":"Resuscitation"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1016\/j.resuscitation.2019.12.042","article-title":"Survival after out-of-hospital cardiac arrest in Europe\u2014Results of the EuReCa TWO study","volume":"148","author":"Grasner","year":"2020","journal-title":"Resuscitation"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1016\/j.emc.2023.05.003","article-title":"Cardiac Arrest as a Public Health Issue","volume":"41","author":"Vazquez","year":"2023","journal-title":"Emerg. Med. Clin. N. Am."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1016\/j.resuscitation.2008.09.017","article-title":"Post-cardiac arrest syndrome: Epidemiology, pathophysiology, treatment, and prognostication. A Scientific Statement from the International Liaison Committee on Resuscitation; the American Heart Association Emergency Cardiovascular Care Committee; the Council on Cardiovascular Surgery and Anesthesia; the Council on Cardiopulmonary, Perioperative, and Critical Care; the Council on Clinical Cardiology; the Council on Stroke","volume":"79","author":"Nolan","year":"2008","journal-title":"Resuscitation"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2126","DOI":"10.1007\/s00134-004-2425-z","article-title":"Mode of death after admission to an intensive care unit following cardiac arrest","volume":"30","author":"Laver","year":"2004","journal-title":"Intensive Care Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1016\/j.bbcan.2012.06.003","article-title":"Ascorbic acid: Chemistry, biology and the treatment of cancer","volume":"1826","author":"Du","year":"2012","journal-title":"Biochim. Biophys. Acta (BBA)-Rev. Cancer"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/j.1742-4658.2006.05607.x","article-title":"Vitamin C. Biosynthesis, recycling and degradation in mammals","volume":"274","author":"Linster","year":"2007","journal-title":"FEBS J."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.freeradbiomed.2020.07.013","article-title":"Ascorbic acid: The chemistry underlying its antioxidant properties","volume":"159","author":"Njus","year":"2020","journal-title":"Free Radic. Biol. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1940","DOI":"10.1007\/s00134-018-5107-y","article-title":"Vitamin therapy in critically ill patients: Focus on thiamine, vitamin C, and vitamin D","volume":"44","author":"Amrein","year":"2018","journal-title":"Intensive Care Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1186\/s13054-017-1891-y","article-title":"Hypovitaminosis C and vitamin C deficiency in critically ill patients despite recommended enteral and parenteral intakes","volume":"21","author":"Carr","year":"2017","journal-title":"Crit. Care"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1016\/B978-0-12-394316-3.00011-9","article-title":"Functional and physiological role of vitamin C transporters","volume":"70","author":"Burzle","year":"2012","journal-title":"Curr. Top. Membr."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1016\/j.freeradbiomed.2008.12.018","article-title":"Vitamin C function in the brain: Vital role of the ascorbate transporter SVCT2","volume":"46","author":"Harrison","year":"2009","journal-title":"Free Radic. Biol. Med."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Linowiecka, K., Foksinski, M., and Brozyna, A.A. (2020). Vitamin C Transporters and Their Implications in Carcinogenesis. Nutrients, 12.","DOI":"10.3390\/nu12123869"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"977","DOI":"10.1007\/s007010050201","article-title":"Effect of ascorbic acid on infarct size in experimental focal cerebral ischaemia and reperfusion in a primate model","volume":"140","author":"Henry","year":"1998","journal-title":"Acta Neurochir."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"11720","DOI":"10.1073\/pnas.171325998","article-title":"Dehydroascorbic acid, a blood-brain barrier transportable form of vitamin C, mediates potent cerebroprotection in experimental stroke","volume":"98","author":"Huang","year":"2001","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1016\/j.jcin.2009.10.025","article-title":"Intravenous ascorbic acid infusion improves myocardial perfusion grade during elective percutaneous coronary intervention: Relationship with oxidative stress markers","volume":"3","author":"Basili","year":"2010","journal-title":"JACC Cardiovasc. Interv."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1111\/acem.12335","article-title":"Combination of intravenous ascorbic acid administration and hypothermia after resuscitation improves myocardial function and survival in a ventricular fibrillation cardiac arrest model in the rat","volume":"21","author":"Tsai","year":"2014","journal-title":"Acad. Emerg. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2033","DOI":"10.1007\/s00134-011-2362-6","article-title":"Ascorbic acid mitigates the myocardial injury after cardiac arrest and electrical shock","volume":"37","author":"Tsai","year":"2011","journal-title":"Intensive Care Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1186\/s13054-018-1996-y","article-title":"Making sense of early high-dose intravenous vitamin C in ischemia\/reperfusion injury","volume":"22","author":"Elbers","year":"2018","journal-title":"Crit. Care"},{"key":"ref_20","first-page":"199","article-title":"Early plasma Vitamin C concentration, organ dysfunction and ICU mortality","volume":"40","author":"Grooth","year":"2014","journal-title":"Intensive Care Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"78","DOI":"10.3945\/an.110.000109","article-title":"Vitamin C: A concentration-function approach yields pharmacology and therapeutic discoveries","volume":"2","author":"Levine","year":"2011","journal-title":"Adv. Nutr."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1016\/S1053-0770(96)80187-X","article-title":"Markers of cerebral ischemia after cardiac surgery","volume":"10","author":"Johnsson","year":"1996","journal-title":"J. Cardiothorac. Vasc. Anesth."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1097\/MCC.0b013e3282f57564","article-title":"Biomarkers of primary and evolving damage in traumatic and ischemic brain injury: Diagnosis, prognosis, probing mechanisms, and therapeutic decision making","volume":"14","author":"Kochanek","year":"2008","journal-title":"Curr. Opin. Crit. Care"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1016\/0002-9149(67)90023-9","article-title":"Treatment of myocardial infarction in a coronary care unit. A two year experience with 250 patients","volume":"20","author":"Killip","year":"1967","journal-title":"Am. J. Cardiol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1229","DOI":"10.1016\/j.chest.2016.11.036","article-title":"Hydrocortisone, Vitamin C, and Thiamine for the Treatment of Severe Sepsis and Septic Shock: A Retrospective Before-After Study","volume":"151","author":"Marik","year":"2017","journal-title":"Chest"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"742","DOI":"10.1001\/jama.2020.24505","article-title":"Effect of Vitamin C, Thiamine, and Hydrocortisone on Ventilator- and Vasopressor-Free Days in Patients With Sepsis: The VICTAS Randomized Clinical Trial","volume":"325","author":"Sevransky","year":"2021","journal-title":"JAMA"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1261","DOI":"10.1001\/jama.2019.11825","article-title":"Effect of Vitamin C Infusion on Organ Failure and Biomarkers of Inflammation and Vascular Injury in Patients With Sepsis and Severe Acute Respiratory Failure: The CITRIS-ALI Randomized Clinical Trial","volume":"322","author":"Fowler","year":"2019","journal-title":"JAMA"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1007\/s00134-021-06558-0","article-title":"Effect of adjunctive vitamin C, glucocorticoids, and vitamin B1 on longer-term mortality in adults with sepsis or septic shock: A systematic review and a component network meta-analysis","volume":"48","author":"Fujii","year":"2022","journal-title":"Intensive Care Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2387","DOI":"10.1056\/NEJMoa2200644","article-title":"Intravenous Vitamin C in Adults with Sepsis in the Intensive Care Unit","volume":"386","author":"Lamontagne","year":"2022","journal-title":"N. Engl. J. Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"562","DOI":"10.1161\/01.CIR.0000023891.80661.AD","article-title":"Successful cardiopulmonary resuscitation after cardiac arrest as a \u201csepsis-like\u201d syndrome","volume":"106","author":"Adrie","year":"2002","journal-title":"Circulation"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1097\/01.ccx.0000126090.06275.fe","article-title":"Postresuscitation disease after cardiac arrest: A sepsis-like syndrome?","volume":"10","author":"Adrie","year":"2004","journal-title":"Curr. Opin. Crit. Care"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1016\/j.resuscitation.2022.08.013","article-title":"The immunology of the post-cardiac arrest syndrome","volume":"179","author":"Cunningham","year":"2022","journal-title":"Resuscitation"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1016\/j.neuropharm.2008.01.005","article-title":"Mechanisms of ischemic brain damage","volume":"55","author":"Doyle","year":"2008","journal-title":"Neuropharmacology"},{"key":"ref_34","unstructured":"Johns, P. (2014). Clinical Neuroscience, Churchill Livingstone."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Lazzarin, T., Tonon, C.R., Martins, D., Favero, E.L., Baumgratz, T.D., Pereira, F.W.L., Pinheiro, V.R., Ballarin, R.S., Queiroz, D.A.R., and Azevedo, P.S. (2022). Post-Cardiac Arrest: Mechanisms, Management, and Future Perspectives. J. Clin. Med., 12.","DOI":"10.3390\/jcm12010259"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/S0079-6123(08)61973-1","article-title":"Selective neuronal vulnerability: Morphological and molecular characteristics","volume":"63","author":"Pulsinelli","year":"1985","journal-title":"Prog. Brain Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1016\/S0891-5849(98)00093-8","article-title":"The basic chemistry of nitrogen monoxide and peroxynitrite","volume":"25","author":"Koppenol","year":"1998","journal-title":"Free Radic. Biol. Med."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1111\/j.1750-3639.1999.tb00214.x","article-title":"Oxidative stress in brain ischemia","volume":"9","author":"Love","year":"1999","journal-title":"Brain Pathol"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1016\/S0196-0644(00)82028-4","article-title":"Molecular mechanisms of ischemic neuronal injury","volume":"36","author":"Neumar","year":"2000","journal-title":"Ann. Emerg. Med."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.biocel.2006.07.001","article-title":"Free radicals and antioxidants in normal physiological functions and human disease","volume":"39","author":"Valko","year":"2007","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1089\/152308603770310266","article-title":"Reactive oxygen radicals and pathogenesis of neuronal death after cerebral ischemia","volume":"5","author":"Sugawara","year":"2003","journal-title":"Antioxid. Redox Signal."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jns.2011.12.007","article-title":"Post-cardiac arrest brain injury: Pathophysiology and treatment","volume":"315","author":"Chalkias","year":"2012","journal-title":"J. Neurol. Sci."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1161\/01.STR.9.5.445","article-title":"Free radicals in cerebral ischemia","volume":"9","author":"Flamm","year":"1978","journal-title":"Stroke"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1016\/j.resuscitation.2021.02.012","article-title":"European Resuscitation Council and European Society of Intensive Care Medicine Guidelines 2021: Post-resuscitation care","volume":"161","author":"Nolan","year":"2021","journal-title":"Resuscitation"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1393","DOI":"10.1007\/s00134-021-06548-2","article-title":"Brain injury after cardiac arrest: Pathophysiology, treatment, and prognosis","volume":"47","author":"Sandroni","year":"2021","journal-title":"Intensive Care Med."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1186\/s13054-017-1670-9","article-title":"Clinical pathophysiology of hypoxic ischemic brain injury after cardiac arrest: A \u201ctwo-hit\u201d model","volume":"21","author":"Sekhon","year":"2017","journal-title":"Crit. Care"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1790","DOI":"10.1046\/j.1471-4159.1995.64041790.x","article-title":"High levels of ascorbic acid, not glutathione, in the CNS of anoxia-tolerant reptiles contrasted with levels in anoxia-intolerant species","volume":"64","author":"Rice","year":"1995","journal-title":"J. Neurochem."},{"key":"ref_48","unstructured":"Amal, H.H. (2017). Vitamin C, IntechOpen."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1126\/science.7901908","article-title":"Oxidative stress, glutamate, and neurodegenerative disorders","volume":"262","author":"Coyle","year":"1993","journal-title":"Science"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1096\/fasebj.1.5.2824268","article-title":"Oxidants and human disease: Some new concepts","volume":"1","author":"Halliwell","year":"1987","journal-title":"FASEB J."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1186\/s40560-020-0432-y","article-title":"Vitamin C may reduce the duration of mechanical ventilation in critically ill patients: A meta-regression analysis","volume":"8","author":"Hemila","year":"2020","journal-title":"J. Intensive Care"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"517","DOI":"10.21470\/1678-9741-2018-0312","article-title":"The Effect of High-Dose Vitamin C on Biochemical Markers of Myocardial Injury in Coronary Artery Bypass Surgery","volume":"34","author":"Emadi","year":"2019","journal-title":"Braz. J. Cardiovasc. Surg."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.ijsu.2016.12.009","article-title":"Efficacy and safety of vitamin C for atrial fibrillation after cardiac surgery: A meta-analysis with trial sequential analysis of randomized controlled trials","volume":"37","author":"Hu","year":"2017","journal-title":"Int. J. Surg."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1002\/clc.22951","article-title":"Sole and combined vitamin C supplementation can prevent postoperative atrial fibrillation after cardiac surgery: A systematic review and meta-analysis of randomized controlled trials","volume":"41","author":"Shi","year":"2018","journal-title":"Clin. Cardiol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"774","DOI":"10.1097\/CCM.0000000000003700","article-title":"The Effect of Vitamin C on Clinical Outcome in Critically Ill Patients: A Systematic Review With Meta-Analysis of Randomized Controlled Trials","volume":"47","author":"Putzu","year":"2019","journal-title":"Crit. Care Med."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"S263","DOI":"10.1007\/s00508-015-0809-4","article-title":"Gender-related differences in patients with ST-elevation myocardial infarction","volume":"127","author":"Sinkovic","year":"2015","journal-title":"Wien. Klin. Wochenschr."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1016\/j.resuscitation.2016.03.001","article-title":"SOFA score to assess the severity of the post-cardiac arrest syndrome","volume":"102","author":"Cour","year":"2016","journal-title":"Resuscitation"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1016\/j.jjcc.2020.03.007","article-title":"The Sequential Organ Failure Assessment (SOFA) score predicts mortality and neurological outcome in patients with post-cardiac arrest syndrome","volume":"76","author":"Matsuda","year":"2020","journal-title":"J. Cardiol."}],"container-title":["Medicina"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1648-9144\/60\/1\/103\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T13:40:43Z","timestamp":1760103643000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1648-9144\/60\/1\/103"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,1,5]]},"references-count":58,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,1]]}},"alternative-id":["medicina60010103"],"URL":"https:\/\/doi.org\/10.3390\/medicina60010103","relation":{},"ISSN":["1648-9144"],"issn-type":[{"value":"1648-9144","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,1,5]]}}}