{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T13:31:20Z","timestamp":1785504680417,"version":"3.56.0"},"reference-count":75,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2024,3,7]],"date-time":"2024-03-07T00:00:00Z","timestamp":1709769600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Cardiac surgery (CS) with extracorporeal circulation (ECC), induces intense oxidative stress (OS) and systemic inflammatory response (SIR), which may seriously affect postoperative lung function. We aimed to test if high parenteral (200 mg\/kg\/24 h) daily doses of Vitamin C (VitC), given within 48 h after the beginning of the operation, may reduce the incidence and severity of postoperative pulmonary complications (PPCs) in CS patients. This single-center, prospective, randomized, single-blinded, interventional trial included 150 patients, assigned to control Group A (n = 75) and interventional Group B (n = 75). Group B intraoperatively received one-fourth (i.e., 50 mg\/kg) of the planned daily Vit C dose, divided into three equal parts and diluted in 10 mL of normal saline, while Group A received an equal volume of normal saline at the same time frames (i.e., the induction of anesthesia, aortic cross-clamp release, and sternal closure). After 6 h from the first intraoperative dose, the following regimen was applied: Group B: 50 mg\/kg, 30 min i.v. infusion of VitC in 50 mL of normal saline, every 6 h, for the next 48 h, and Group A: 30 min i.v. infusion of an equal volume of normal saline every 6 h, for the next 48 h. Modified Kroenke\u2019s score was used to determine the incidence and severity of PPCs. The overall incidence of PPCs was 36.7% and was significantly lower in Group B (13.3% vs. 60.0%, p &lt; 0.001). The PPCs severity score was also significantly lower in Group B (1 vs. 3, p &lt; 0.001). In addition, patients from Group B had significantly less damaged lungs, better postoperative renal function, shorter ICU stays, fewer ICU re-admissions, and lower hospital mortality. No VitC-related adverse effects were recorded. High parenteral daily VitC doses given within 48 h after the beginning of CS are safe and effective in reducing the incidence and severity of PPCs. A multicenter RCT is needed to confirm these results.<\/jats:p>","DOI":"10.3390\/nu16060761","type":"journal-article","created":{"date-parts":[[2024,3,7]],"date-time":"2024-03-07T11:33:06Z","timestamp":1709811186000},"page":"761","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["The Influence of High-Dose Parenteral Vitamin C on the Incidence and Severity of Postoperative Pulmonary Complications in Cardiac Surgery with Extracorporeal Circulation: A Randomized Controlled Trial"],"prefix":"10.3390","volume":"16","author":[{"given":"Milica","family":"Karad\u017ei\u0107 Ko\u010dica","sequence":"first","affiliation":[{"name":"Department of Anesthesiology, Reanimatology and Intensive Care, Clinic for Cardiac Surgery, University Clinical Centre of Serbia, 11000 Belgrade, Serbia"},{"name":"Medical Faculty, University of Belgrade, 11000 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0713-1180","authenticated-orcid":false,"given":"Arsen","family":"Risti\u0107","sequence":"additional","affiliation":[{"name":"Medical Faculty, University of Belgrade, 11000 Belgrade, Serbia"},{"name":"Clinic for Cardiology, University Clinical Centre of Serbia, 11000 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4893-1683","authenticated-orcid":false,"given":"Ivan","family":"Soldatovi\u0107","sequence":"additional","affiliation":[{"name":"Medical Faculty, University of Belgrade, 11000 Belgrade, Serbia"},{"name":"Department of Medical Statistics and Informatics, Medical Faculty, University of Belgrade, 11000 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dejan","family":"Lazovi\u0107","sequence":"additional","affiliation":[{"name":"Medical Faculty, University of Belgrade, 11000 Belgrade, Serbia"},{"name":"Clinic for Cardiac Surgery, University Clinical Centre of Serbia, 11000 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jelena","family":"\u010cumi\u0107","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Reanimatology and Intensive Care, Clinic for Cardiac Surgery, University Clinical Centre of Serbia, 11000 Belgrade, Serbia"},{"name":"Medical Faculty, University of Belgrade, 11000 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Milo\u0161","family":"Gruji\u0107","sequence":"additional","affiliation":[{"name":"Medical Faculty, University of Belgrade, 11000 Belgrade, Serbia"},{"name":"Clinic for Cardiac Surgery, University Clinical Centre of Serbia, 11000 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8713-4356","authenticated-orcid":false,"given":"Radmila","family":"Karan","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Reanimatology and Intensive Care, Clinic for Cardiac Surgery, University Clinical Centre of Serbia, 11000 Belgrade, Serbia"},{"name":"Medical Faculty, University of Belgrade, 11000 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Du\u0161ko","family":"Terzi\u0107","sequence":"additional","affiliation":[{"name":"Medical Faculty, University of Belgrade, 11000 Belgrade, Serbia"},{"name":"Clinic for Cardiac Surgery, University Clinical Centre of Serbia, 11000 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivan","family":"Palibrk","sequence":"additional","affiliation":[{"name":"Medical Faculty, University of Belgrade, 11000 Belgrade, Serbia"},{"name":"Department of Anesthesiology, Reanimatology and Intensive Care, Clinic for Abdominal Surgery, University Clinical Centre of Serbia, 11000 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1391-5053","authenticated-orcid":false,"given":"Mladen","family":"Ko\u010dica","sequence":"additional","affiliation":[{"name":"Clinic for Cardiac Surgery, University Clinical Centre of Serbia, 11000 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5167-4388","authenticated-orcid":false,"given":"Dejan","family":"Markovi\u0107","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Reanimatology and Intensive Care, Clinic for Cardiac Surgery, University Clinical Centre of Serbia, 11000 Belgrade, Serbia"},{"name":"Medical Faculty, University of Belgrade, 11000 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,3,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1682","DOI":"10.1053\/j.jvca.2019.01.043","article-title":"Prevalence and Clinical Impact of Systemic Inflammatory Reaction After Cardiac Surgery","volume":"33","author":"Squiccimarro","year":"2019","journal-title":"J. Cardiothorac. Vasc. Anesth."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"958","DOI":"10.1164\/rccm.201502-0275OC","article-title":"Incidence and Prognostic Value of the Systemic Inflammatory Response Syndrome and Organ Dysfunctions in Ward Patients","volume":"192","author":"Churpek","year":"2015","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1016\/S1479-666X(08)80113-8","article-title":"Understanding the inflammatory response to cardiac surgery","volume":"6","author":"McGuinness","year":"2008","journal-title":"Surgeon"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1181","DOI":"10.1378\/chest.14-0438","article-title":"Systemic inflammatory response syndrome after cardiac surgery: Time for a change","volume":"145","author":"Semler","year":"2014","journal-title":"Chest"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1097\/00000542-200207000-00030","article-title":"The Systemic Inflammatory Response to Cardiac Surgery: Implications for the Anesthesiologist","volume":"97","author":"Warltier","year":"2002","journal-title":"Anesthesiology"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1197","DOI":"10.1378\/chest.13-1023","article-title":"Modified criteria for the systemic inflammatory response syndrome improves their utility following cardiac surgery","volume":"145","author":"MacCallum","year":"2014","journal-title":"Chest"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1111\/jocs.14331","article-title":"Validation of prognostic accuracy of the SOFA score, SIRS criteria, and qSOFA score for in-hospital mortality among cardiac-, thoracic-, and vascular-surgery patients admitted to a cardiothoracic intensive care unit","volume":"35","author":"Zhang","year":"2020","journal-title":"J. Card. Surg."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1016\/S1010-7940(03)00295-1","article-title":"Biological effects of off-pump vs. on-pump coronary artery surgery: Focus on inflammation, hemostasis and oxidative stress","volume":"24","author":"Biglioli","year":"2003","journal-title":"Eur. J. Cardio-Thorac. Surg."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1051\/ject\/201446197","article-title":"Attenuating the Systemic Inflammatory Response to Adult Cardiopulmonary Bypass: A Critical Review of the Evidence Base","volume":"46","author":"Landis","year":"2014","journal-title":"J. Extra-Corpor. Technol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1016\/j.bpa.2003.12.004","article-title":"Inflammatory response to cardiac surgery: Cardiopulmonary bypass versus non-cardiopulmonary bypass surgery","volume":"18","author":"Larmann","year":"2004","journal-title":"Best. Pract. Res. Clin. Anaesthesiol."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Wang, J., and Wu, Y. (2024). Mass intraoperative endothelial glycocalyx shedding affects postoperative systemic inflammation response. BMC Anesthesiol., 24.","DOI":"10.1186\/s12871-024-02459-z"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1093\/bjaceaccp\/mks060","article-title":"Non-respiratory functions of the lung","volume":"13","author":"Joseph","year":"2013","journal-title":"Contin. Educ. Anaesth. Crit. Care Pain"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1093\/bja\/aex002","article-title":"Postoperative pulmonary complications","volume":"118","author":"Miskovic","year":"2017","journal-title":"Br. J. Anaesth."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2344","DOI":"10.1053\/j.jvca.2021.12.024","article-title":"Postoperative Pulmonary Complications After Cardiac Surgery: The VENICE International Cohort Study","volume":"36","author":"Fischer","year":"2022","journal-title":"J. Cardiothorac. Vasc. Anesth."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1980","DOI":"10.1016\/j.athoracsur.2008.01.053","article-title":"The frequency and cost of complications associated with coronary artery bypass grafting surgery: Results from the United States Medicare program","volume":"85","author":"Brown","year":"2008","journal-title":"Ann. Thorac. Surg."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1066","DOI":"10.1016\/j.bja.2018.02.007","article-title":"A systematic review and consensus definitions for standardised end-points in perioperative medicine: Pulmonary complications","volume":"120","author":"Abbott","year":"2018","journal-title":"Br. J. Anaesth."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e280","DOI":"10.5114\/amsad.2019.91432","article-title":"Pulmonary complications following cardiac surgery","volume":"4","author":"Mali","year":"2019","journal-title":"Arch. Med. Sci. Atheroscler. Dis."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1080\/00325481.1992.11701233","article-title":"Postoperative pulmonary complications. When are preventive and therapeutic measures necessary?","volume":"91","year":"1992","journal-title":"Postgrad. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1097\/EJA.0000000000000118","article-title":"Standards for definitions and use of outcome measures for clinical effectiveness research in perioperative medicine: European Perioperative Clinical Outcome (EPCO) definitions: A statement from the ESA-ESICM joint taskforce on perioperative outcome measures","volume":"32","author":"Jammer","year":"2015","journal-title":"Eur. J. Anaesthesiol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1422","DOI":"10.1001\/jama.2017.2297","article-title":"Effect of Intensive vs Moderate Alveolar Recruitment Strategies Added to Lung-Protective Ventilation on Postoperative Pulmonary Complications: A Randomized Clinical Trial","volume":"317","author":"Hajjar","year":"2017","journal-title":"JAMA"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1056\/NEJMoa1301082","article-title":"A trial of intraoperative low-tidal-volume ventilation in abdominal surgery","volume":"369","author":"Futier","year":"2013","journal-title":"N. Engl. J. Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1851","DOI":"10.1001\/jama.296.15.1851","article-title":"Preoperative intensive inspiratory muscle training to prevent postoperative pulmonary complications in high-risk patients undergoing CABG surgery: A randomized clinical trial","volume":"296","author":"Hulzebos","year":"2006","journal-title":"JAMA"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"967","DOI":"10.1001\/archinte.1992.00400170057011","article-title":"Operative risk in patients with severe obstructive pulmonary disease","volume":"152","author":"Kroenke","year":"1992","journal-title":"Arch. Intern. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1186\/s13054-014-0460-x","article-title":"Vitamin C revisited","volume":"18","year":"2014","journal-title":"Crit. Care"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1016\/S0022-5223(94)70013-3","article-title":"Depletion of plasma vitamin C but not of vitamin E in response to cardiac operations","volume":"108","author":"Ballmer","year":"1994","journal-title":"J. Thorac. Cardiovasc. Surg."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"7180","DOI":"10.4049\/jimmunol.165.12.7180","article-title":"Vitamin C inhibits NF-kappa B activation by TNF via the activation of p38 mitogen-activated protein kinase","volume":"165","author":"Bowie","year":"2000","journal-title":"J. Immunol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"533","DOI":"10.7326\/0003-4819-140-7-200404060-00010","article-title":"Vitamin C pharmacokinetics: Implications for oral and intravenous use","volume":"140","author":"Padayatty","year":"2004","journal-title":"Ann. Intern. Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2171","DOI":"10.1093\/jn\/137.10.2171","article-title":"New developments and novel therapeutic perspectives for vitamin C","volume":"137","author":"Li","year":"2007","journal-title":"J. Nutr."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1097\/MCO.0b013e32833e05bc","article-title":"Vitamin C requirement in surgical patients","volume":"13","author":"Fukushima","year":"2010","journal-title":"Curr. Opin. Clin. Nutr. Metab. Care"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Lykkesfeldt, J., and Tveden-Nyborg, P. (2019). The Pharmacokinetics of Vitamin C. Nutrients, 11.","DOI":"10.3390\/nu11102412"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1123","DOI":"10.1053\/j.jvca.2019.09.018","article-title":"Power for the Sickest: Vitamin C for Vasoplegia after Cardiac Surgery","volume":"34","author":"Long","year":"2020","journal-title":"J. Cardiothorac. Vasc. Anesth."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Lykkesfeldt, J. (2020). On the effect of vitamin C intake on human health: How to (mis)interprete the clinical evidence. Redox Biol., 34.","DOI":"10.1016\/j.redox.2020.101532"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Dosed\u011bl, M., Jirkovsk\u00fd, E., Mac\u00e1kov\u00e1, K., Kr\u010dmov\u00e1, L.K., Javorsk\u00e1, L., Pourov\u00e1, J., Mercolini, L., Remi\u00e3o, F., Nov\u00e1kov\u00e1, L., and Mlad\u011bnka, P. (2021). Vitamin C-Sources, Physiological Role, Kinetics, Deficiency, Use, Toxicity, and Determination. Nutrients, 13.","DOI":"10.3390\/nu13020615"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Hill, A., Clasen, K.C., Wendt, S., Majoros, \u00c1.G., Stoppe, C., Adhikari, N.K., Heyland, D.K., and Benstoem, C. (2019). Effects of Vitamin C on Organ Function in Cardiac Surgery Patients: A Systematic Review and Meta-Analysis. Nutrients, 11.","DOI":"10.3390\/nu11092103"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Hill, A., Borgs, C., Fitzner, C., and Stoppe, C. (2019). Perioperative Vitamin C and E levels in Cardiac Surgery Patients and Their Clinical Significance. Nutrients, 11.","DOI":"10.3390\/nu11092157"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Hill, A., Wendt, S., Benstoem, C., Neubauer, C., Meybohm, P., Langlois, P., Adhikari, N.K., Heyland, D.K., and Stoppe, C. (2018). Vitamin C to Improve Organ Dysfunction in Cardiac Surgery Patients-Review and Pragmatic Approach. Nutrients, 10.","DOI":"10.20944\/preprints201806.0444.v1"},{"key":"ref_37","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_38","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1056\/NEJM197909273011303","article-title":"Failure of high-dose vitamin C (ascorbic acid) therapy to benefit patients with advanced cancer. A controlled trial","volume":"301","author":"Creagan","year":"1979","journal-title":"N. Engl. J. Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1294","DOI":"10.1093\/ajcn\/24.11.1294","article-title":"Ascorbic acid and the common cold","volume":"24","author":"Pauling","year":"1971","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Coppock, D., Violet, P.C., Vasquez, G., Belden, K., Foster, M., Mullin, B., Magee, D., Mikell, I., Shah, L., and Powers, V. (2022). Pharmacologic Ascorbic Acid as Early Therapy for Hospitalized Patients with COVID-19: A Randomized Clinical Trial. Life, 12.","DOI":"10.3390\/life12030453"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1186\/s13613-020-00792-3","article-title":"Pilot trial of high-dose vitamin C in critically ill COVID-19 patients","volume":"11","author":"Zhang","year":"2021","journal-title":"Ann. Intensive Care"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"100028","DOI":"10.1016\/j.medidd.2020.100028","article-title":"Can early and high intravenous dose of vitamin C prevent and treat coronavirus disease 2019 (COVID-19)?","volume":"5","author":"Cheng","year":"2020","journal-title":"Med. Drug Discov."},{"key":"ref_43","unstructured":"PDQ\u00ae Integrative (2023, October 12). Alternative, and Complementary Therapies Editorial Board, Available online: https:\/\/www.cancer.gov\/about-cancer\/treatment\/cam\/hp\/vitamin-c-pdq."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1186\/1479-5876-12-32","article-title":"Phase I safety trial of intravenous ascorbic acid in patients with severe sepsis","volume":"12","author":"Fowler","year":"2014","journal-title":"J. Transl. Med."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1055\/s-2007-1016504","article-title":"The protective effects of high-dose ascorbic acid on myocardium against reperfusion injury during and after cardiopulmonary bypass","volume":"42","author":"Dingchao","year":"1994","journal-title":"Thorac. Cardiovasc. Surg."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1237","DOI":"10.1007\/s40262-022-01142-1","article-title":"Pharmacokinetic Evaluation of Intravenous Vitamin C: A Classic Pharmacokinetic Study","volume":"61","author":"Chen","year":"2022","journal-title":"Clin. Pharmacokinet."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"e620","DOI":"10.1097\/CCM.0000000000004396","article-title":"Harm of IV High-Dose Vitamin C Therapy in Adult Patients: A Scoping Review","volume":"48","author":"Yanase","year":"2020","journal-title":"Crit. Care Med."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1912","DOI":"10.1161\/01.CIR.0000064899.53876.A3","article-title":"Ascorbic acid enhances differentiation of embryonic stem cells into cardiac myocytes","volume":"107","author":"Takahashi","year":"2003","journal-title":"Circulation"},{"key":"ref_49","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_50","doi-asserted-by":"crossref","first-page":"2068","DOI":"10.1089\/ars.2013.5205","article-title":"Role of vitamin C in the function of the vascular endothelium","volume":"19","author":"May","year":"2013","journal-title":"Antioxid. Redox Signal."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.atherosclerosis.2014.04.004","article-title":"Effect of vitamin C on endothelial function in health and disease: A systematic review and meta-analysis of randomised controlled trials","volume":"235","author":"Ashor","year":"2014","journal-title":"Atherosclerosis"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"789729","DOI":"10.3389\/fcvm.2022.789729","article-title":"Vitamin C May Improve Left Ventricular Ejection Fraction: A Meta-Analysis","volume":"9","author":"Chalker","year":"2022","journal-title":"Front. Cardiovasc. Med."},{"key":"ref_53","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":"Chalker","year":"2020","journal-title":"J. Intensive Care"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1016\/S1010-7940(03)00436-6","article-title":"Effect of ascorbic acid on endothelium-dependent vasodilatation of human arterial conduits for coronary artery bypass grafting","volume":"24","author":"Mangoush","year":"2003","journal-title":"Eur. J. Cardiothorac. Surg."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"3263","DOI":"10.2147\/DDDT.S254150","article-title":"Effect of Intravenous Injection of Vitamin C on Postoperative Pulmonary Complications in Patients Undergoing Cardiac Surgery: A Double-Blind, Randomized Trial","volume":"14","author":"Wang","year":"2020","journal-title":"Drug Des. Devel. Ther."},{"key":"ref_56","first-page":"16","article-title":"Changes of creatine phosphokinase and malondialdehyde in the serum and clinical use of large doses of vitamin C following open heart surgery","volume":"28","author":"Li","year":"1990","journal-title":"Zhonghua Wai Ke Za Zhi"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1186\/s13741-018-0094-7","article-title":"Clinical agreement in the American Society of Anesthesiologists physical status classification","volume":"7","author":"Knuf","year":"2018","journal-title":"Perioper. Med."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1186\/s13054-019-2663-7","article-title":"The SOFA score-development, utility and challenges of accurate assessment in clinical trials","volume":"23","author":"Lambden","year":"2019","journal-title":"Crit. Care"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1442","DOI":"10.1053\/j.jvca.2023.03.031","article-title":"Comparison of Tools for Postoperative Pulmonary Complications After Cardiac Surgery","volume":"37","author":"Wang","year":"2023","journal-title":"J. Cardiothorac. Vasc. Anesth."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Cvetkovi\u0107, V.M., Nikoli\u0107, N., Radovanovi\u0107 Nenadi\u0107, U., \u00d6cal, A., Noji, E.K., and Ze\u010devi\u0107, M. (2020). Preparedness and Preventive Behaviors for a Pandemic Disaster Caused by COVID-19 in Serbia. Int. J. Environ. Res. Public Health, 17.","DOI":"10.3390\/ijerph17114124"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1186\/s13019-021-01669-7","article-title":"Incidence of postoperative pulmonary complications in patients undergoing minimally invasive versus median sternotomy valve surgery: Propensity score matching","volume":"16","author":"Mohamed","year":"2021","journal-title":"J. Cardiothorac. Surg."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1007\/s00408-020-00405-7","article-title":"Pulmonary Complications of Cardiac Surgery","volume":"198","author":"Tanner","year":"2020","journal-title":"Lung"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"993","DOI":"10.12669\/pjms.334.12846","article-title":"Incidence and risk factors of Pulmonary Complications after Cardiopulmonary bypass","volume":"33","author":"Naveed","year":"2017","journal-title":"Pak. J. Med. Sci."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1097\/EJA.0b013e328344be2d","article-title":"PERISCOPE study: Predicting post-operative pulmonary complications in Europe","volume":"28","author":"Canet","year":"2011","journal-title":"Eur. J. Anaesthesiol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1338","DOI":"10.1097\/ALN.0b013e3181fc6e0a","article-title":"Prediction of postoperative pulmonary complications in a population-based surgical cohort","volume":"113","author":"Canet","year":"2010","journal-title":"Anesthesiology"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1177\/108925320400800303","article-title":"Pulmonary complications after cardiac surgery","volume":"8","author":"Weissman","year":"2004","journal-title":"Semin. Cardiothorac. Vasc. Anesth."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"12","DOI":"10.3389\/fcvm.2016.00012","article-title":"Lung-Centered Open Heart Surgery: A Call for a Paradigm Change","volume":"3","author":"Gologorsky","year":"2016","journal-title":"Front. Cardiovasc. Med."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1007\/s11886-015-0587-7","article-title":"Racial disparities in outcomes after cardiac surgery: The role of hospital quality","volume":"17","author":"Khera","year":"2015","journal-title":"Curr. Cardiol. Rep."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1046","DOI":"10.1097\/ALN.0000000000002909","article-title":"Intraoperative Mechanical Ventilation and Postoperative Pulmonary Complications after Cardiac Surgery","volume":"131","author":"Mathis","year":"2019","journal-title":"Anesthesiology"},{"key":"ref_70","unstructured":"Hickey, S., and Roberts, H. (2004). Ascorbate: The Science of Vitamin C, Lulu Press."},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Rowe, S., and Carr, A.C. (2020). Global Vitamin C Status and Prevalence of Deficiency: A Cause for Concern?. Nutrients, 12.","DOI":"10.3390\/nu12072008"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1159\/000343121","article-title":"The discovery of vitamin C","volume":"61","author":"Carpenter","year":"2012","journal-title":"Ann. Nutr. Metab."},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Richards, E. (1991). Vitamin C and Cancer: Medicine or Politics?, Palgrave Macmillan UK.","DOI":"10.1007\/978-1-349-09606-0"},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Iizuka, Y., Yoshinaga, K., Takahashi, K., Oki, S., Chiba, Y., Sanui, M., Kimura, N., and Yamaguchi, A. (2023). Association between Plasma Ascorbic Acid Levels and Postoperative Delirium in Older Patients Undergoing Cardiovascular Surgery: A Prospective Observational Study. J. Cardiovasc. Dev. Dis., 10.","DOI":"10.3390\/jcdd10070293"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"52","DOI":"10.5492\/wjccm.v7.i5.52","article-title":"Vitamin C in the critically ill\u2014indications and controversies","volume":"7","author":"Nabzdyk","year":"2018","journal-title":"World J. Crit. Care Med."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/16\/6\/761\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:10:13Z","timestamp":1760105413000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/16\/6\/761"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,3,7]]},"references-count":75,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2024,3]]}},"alternative-id":["nu16060761"],"URL":"https:\/\/doi.org\/10.3390\/nu16060761","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,3,7]]}}}