Effect of vitamin C on coagulation factors and endothelium function in patients with sepsis

Abstract

Objective: Sepsis is one of the leading causes of mortality in intensive care unit. Despite advances in its management, its mortality rate remains high. Recently, high dose of vitamin C in sepsis treatment has attracted the attention of researchers. In the current study, the impacts of 25 mg/kg of vitamin C every 6 hours as a bolus for 3 days were assessed in septic patients in intensive care unit (ICU). Methods: This was a prospective cohort study that was performed on adult patients with diagnosis of sepsis. Patients were assigned to control group (administration of placebo) or intervention group, i.e., those receiving a 25 mg/kg dose of vitamin C every 6 hours as a bolus for 3 days. Clinical data were recorded before and after the experiment. Also, plasma levels of antithrombin III, syndecan-1, fibrin degradation product (FDP), D-dimer, and C-reactive protein (CRP) were measured at 0, 24, 48, and 72 hours. Results: In septic patients receiving vitamin C, a significant upregulation of antithrombin III and significant decreases in the levels of syndecan-1 (at 48 hours; P-value=0.046 and at 72 hours; P-value=0.007), D-dimer and CRP were observed compared to the control. Reductions in sequential organ failure assessment (SOFA) score, in-hospital mortality, and ICU length of stay were seen in septic patients receiving vitamin C. Conclusion: Prescribing high dose of intravenous vitamin C can reduce the mortality of sepsis patients and reduce the length of stay in the ICU.

1. Gyawali B, Ramakrishna K, Dhamoon AS. Sepsis: the evolution in definition, pathophysiology, and management. SAGE Open Med. 2019;7:2050312119835043.
2. Dolmatova EV, Wang K, Mandavilli R, Griendling KK. The effects of sepsis on endothelium and clinical implications. Cardiovasc Res. 2021;117(1):60-73.
3. Reitsma S, Slaaf DW, Vink H, van Zandvoort MA, oude Egbrink MG. The endothelial glycocalyx: composition, functions, and visualization. Pflugers Arch. 2007;454(3):345-59.
4. Uchimido R, Schmidt EP, Shapiro NI. The glycocalyx: a novel diagnostic and therapeutic target in sepsis. Crit Care. 2019;23(1):16.
5. Teng YH, Aquino RS, Park PW. Molecular functions of syndecan-1 in disease. Matrix Biol. 2012;31(1):3-16.
6. Ikeda M, Matsumoto H, Ogura H, Hirose T, Shimizu K, Yamamoto K, et al. Circulating syndecan-1 predicts the development of disseminated intravascular coagulation in patients with sepsis. J Crit Care. 2018;43:48-53.
7. Iba T, Levy JH, Raj A, Warkentin TE. Advance in the management of sepsis-induced coagulopathy and disseminated intravascular coagulation. J Clin Med. 2019;8(5):728.
8. Hepner M, Karlaftis V. Antithrombin. Methods Mol Biol. 2013;992:355-64.
9. Fowler AA 3rd, Syed AA, Knowlson S, Sculthorpe R, Farthing D, DeWilde C, et al. Phase I safety trial of intravenous ascorbic acid in patients with severe sepsis. J Transl Med. 2014;12:32.
10. Zabet MH, Mohammadi M, Ramezani M, Khalili H. Effect of high-dose ascorbic acid on vasopressor's requirement in septic shock. J Res Pharm Pract. 2016;5(2):94-100.
11. May JM, Qu ZC, Meredith ME. Mechanisms of ascorbic acid stimulation of norepinephrine synthesis in neuronal cells. Biochem Biophys Res Commun. 2012;426(1):148-52.
12. Lavillegrand JR, Raia L, Urbina T, Hariri G, Gabarre P, Bonny V, et al. Vitamin C improves microvascular reactivity and peripheral tissue perfusion in septic shock patients. Crit Care. 2022;26(1):25.
13. Marik PE, Khangoora V, Rivera R, Hooper MH, Catravas J. Hydrocortisone, vitamin C, and thiamine for the treatment of severe sepsis and septic shock: a retrospective before-after study. Chest. 2017;151(6):1229-38.14. Vincent J-L, Moreno R, Takala J, Willatts S, De Mendonça A, Bruining H, et al. The SOFA (sepsis-related organ failure assessment) score to describe organ dysfunction/failure. On behalf of the working group on sepsis-related problems of the european society of intensive care medicine. Springer-Verlag; 1996.
15. Taylor FB Jr, Toh CH, Hoots WK, Wada H, Levi M. Towards definition, clinical and laboratory criteria, and a scoring system for disseminated intravascular coagulation. Thromb Haemost. 2001;86(5):1327-30.
16. Kashiouris MG, L'Heureux M, Cable CA, Fisher BJ, Leichtle SW, Fowler AA. The emerging role of vitamin C as a treatment for sepsis. Nutrients. 2020;12(2):292.
17. Nieboer P, van der Werf TS, Beentjes JA, Tulleken JE, Zijlstra JG, Ligtenberg JJ. Catecholamine dependency in a polytrauma patient: relative adrenal insufficiency? Intensive Care Med. 2000;26(1):125-7.
18. Wilson JX. Mechanism of action of vitamin C in sepsis: ascorbate modulates redox signaling in endothelium. Biofactors. 2009;35(1):5-13.
19. Hamzaoui O, Scheeren TWL, Teboul JL. Norepinephrine in septic shock: when and how much? Curr Opin Crit Care. 2017;23(4):342-7.
20. Carr AC, Shaw GM, Fowler AA, Natarajan R. Ascorbate-dependent vasopressor synthesis: a rationale for vitamin C administration in severe sepsis and septic shock? Crit Care. 2015;19:418.
21. Balakrishnan M, Gandhi H, Shah K, Pandya H, Patel R, Keshwani S, et al. Hydrocortisone, vitamin C and thiamine for the treatment of sepsis and septic shock following cardiac surgery. Indian J Anaesth. 2018;62(12):934-9.
22. Wandzilak TR, D'Andre SD, Davis PA, Williams HE. Effect of high dose vitamin C on urinary oxalate levels. J Urol. 1994;151(4):834-7.
23. Steppan J, Hofer S, Funke B, Brenner T, Henrich M, Martin E, et al. Sepsis and major abdominal surgery lead to flaking of the endothelial glycocalix. J Surg Res. 2011;165(1):136-41.
24. Mavrommatis AC, Theodoridis T, Economou M, Kotanidou A, El Ali M, Christopoulou-Kokkinou V, et al. Activation of the fibrinolytic system and utilization of the coagulation inhibitors in sepsis: comparison with severe sepsis and septic shock. Intensive Care Med. 2001;27(12):1853-9.
25. El Beshlawy A, Alaraby I, Abou Hussein H, Abou-Elew HH, Mohamed Abdel Kader MS. Study of protein C, protein S, and antithrombin III in newborns with sepsis. Pediatr Crit Care Med. 2010;11(1):52-9.
26. Kario K, Matsuo T, Kabayashi H, Matsuo M, Yamamoto K, Sakurai G, et al. Rapid quantitative evaluation of plasma D-dimer levels in thrombotic states using an automated latex photometric immunoassay. Thromb Res. 1992;66(2-3):179-89.
Files
IssueVol 7 No 2 (2023): Spring (April) QRcode
SectionOriginal article
DOI 10.18502/fem.v7i2.12768
Keywords
Acid Ascorbic Blood Coagulation Endothelium Sepsis Syndecan-1
Rights and permissions
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
How to Cite
1.
Amini K, Mojtahedzadeh M, Najafi A, Sharifnia H, Tabatabaei Mohammadi A. Effect of vitamin C on coagulation factors and endothelium function in patients with sepsis. Front Emerg Med. 2023;7(2):e16.

Downloads

Download data is not yet available.