Journal of Acute Care

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VOLUME 1 , ISSUE 2 ( May-August, 2022 ) > List of Articles

Original Article

Outcome of Septic Shock Patients treated with Vitamin C and Thiamine: A Prospective Cohort Study

Marutheesh Mallappa, Suman S Reddy, Sarika Kunwar

Keywords : Ascorbic acid, Ascorbic acid and thiamine protocol, Hydrocortisone, Mortality, Sepsis, Septic shock, Vitamin C

Citation Information : Mallappa M, Reddy SS, Kunwar S. Outcome of Septic Shock Patients treated with Vitamin C and Thiamine: A Prospective Cohort Study. 2022; 1 (2):56-60.

DOI: 10.5005/jp-journals-10089-0031

License: CC BY-NC 4.0

Published Online: 31-12-2022

Copyright Statement:  Copyright © 2022; The Author(s).


Background: Although there has been great progress in the field of medicine, mortality associated with the age-old problem of sepsis still remains high. One of the newer modalities to treat sepsis is the hydrocortisone, ascorbic acid (AA), and thiamine (HAT) therapy, using HAT, which is proposed to reduce organ failure and mortality by restoring dysregulated host immune response and mitochondrial function as well as neutralizing reactive oxygen species (ROS). Studies evaluating the treatment of severe sepsis, burns, and trauma with vitamin C administration have shown inconsistent results. Several studies have also shown the detrimental effect of a positive fluid balance on patients with sepsis, including an increased risk of mortality. This study aims to evaluate the effect of vitamin C with thiamine on improving the outcome of septic shock. Materials and methods: This prospective cohort study was conducted at a tertiary care intensive care unit (ICU) and enrolled adult septic shock patients admitted over a 6-month period between April and September 2018. They formed an intervention group that received intravenous (IV) vitamin C 1.5 gm every 6 hours and thiamine 200 mg every 12 hours in addition to antibiotics. This was compared with a retrospective cohort of patients admitted between July to December 2017, which received only antibiotics. Both vitamin C and thiamine were initiated within 6 hours of admission and given for a period of 4 days. Hydrocortisone, as an infusion of 200 mg over 24 hours, was used in all patients on vasopressor support. The primary outcome evaluated was ICU mortality and secondary outcomes, ICU length of stay (LOS), hospital LOS, mechanical ventilation-free days (MVFDs), vasopressor-free days (VFDs), and cumulative fluid balance after 4 days. Results: A total of 30 patients fulfilled the inclusion criteria and formed the intervention group. This was compared with a retrospective group which was equally matched in their baseline characteristics and acute physiology and chronic health evaluation (APACHE) II scores (20 vs 21), as well as antibiotics, are given. ICU mortality was 19% in the intervention group and 34.1% in the retrospective group (p = 0.115). ICU LOS was higher in the intervention group (5 vs 4 days, p = 0.014). There was no difference in the other secondary outcome parameters, namely, hospital LOS (10 vs 8 days, p = 0.141), MVFDs (5 vs 6, p = 0.493), VFDs (4 vs 6, p = 0.415), and cumulative fluid balance (+583 mL vs +450 mL, p = 0.209). Conclusion: Intravenous (IV) administration of vitamin C and thiamine may not be beneficial in improving the outcome in patients with septic shock.

  1. Singer M, Deutschman CS, Seymour CW, et al. The third international consensus definitions for sepsis and septic shock (sepsis-3). JAMA 2016;315(8):801–810. DOI: 10.1001/ jama.2016.0287
  2. Fleischmann C, Scherag A, Adhikari NK, et al. Assessment of global incidence and mortality of hospital-treated sepsis. current estimates and limitations. Am J Respir Crit Care Med 2016;193(3):259–272. DOI: 10.1164/rccm.201504- 0781OC
  3. Hotchkiss RS, Moldawer LL, Opal SM, et al. Sepsis and septic shock. Nat Rev Dis Prim 2016;2(1):16045. DOI: 10.1038/nrdp.2016.45
  4. Mantzarlis K, Tsolaki V, Zakynthinos E. Role of oxidative stress and mitochondrial dysfunction in sepsis and potential therapies. Oxid Med Cell Longev 2017;2017(7):5985209. DOI: 10.1155/2017/5985209
  5. De Backer D, Cortes DO, Donadello K, et al. Pathophysiology of microcirculatory dysfunction and the pathogenesis of septic shock. Virulence 2014;5(1): 73–79. DOI: 10.4161/viru.26482
  6. Wilson JX. Mechanism of action of vitamin C in sepsis: ascorbate modulates redox signaling in endothelium. Biofactors 2009;35(1):5–13. DOI: 10.1002/biof.7
  7. Borrelli E, Roux-Lombard P, Grau GE, et al. Plasma concentrations of cytokines, their soluble receptors, and antioxidant vitamins can predict the development of multiple organ failure in patients at risk. Crit Care Med 1996 Mar;24(3):392–397. DOI: 10.1097/00003246-199603000-00006
  8. Biesalski HK, McGregor GP. Antioxidant therapy in critical care–is the microcirculation the primary target? Crit Care Med 2007;35(9 Suppl):S577–S583. DOI: 10.1097/01.CCM.0000278598.95294.C5
  9. Burke-Gaffney A, Evans TW. Lest we forget the endothelial glycocalyx in sepsis. Crit Care 2012;16(2):121. DOI: 10.1186/cc11239
  10. Belsky JB, Wira CR, Jacob V, et al. A review of micronutrients in sepsis: the role of thiamine, l-carnitine, vitamin C, selenium and vitamin D. Nutr Res Rev 2018;31(2):281–290. DOI: 10.1017/S0954422418000124
  11. Woolum JA, Abner EL, Kelly A, et al. Effect of thiamine administration on lactate clearance and mortality in patients with septic shock. Crit Care Med 2018;46(11):1747–1752. DOI: 10.1097/CCM.0000000000003311
  12. Shangari N, Bruce WR, Poon R, et al. Toxicity of glyoxals–role of oxidative stress, metabolic detoxification and thiamine deficiency. Biochem Soc Trans 2003;31(Pt 6):1390–1393. DOI: 10.1042/bst0311390
  13. Spoelstra-de Man AME, Oudemans-van Straaten HM, Elbers PWG. Vitamin C and thiamine in critical illness. BJA Educ 2019;19(9):290–296. DOI: 10.1016/j.bjae.2019.05.005
  14. Venkatesh B, Finfer S, Cohen J, et al. Adjunctive glucocorticoid therapy in patients with septic shock. N Engl J Med 2018;378(9):797–808. DOI: 10.1056/NEJMoa1705835
  15. Marik PE, Khangoora V, Rivera R, et al. Hydrocortisone, vitamin C, and thiamine for the treatment of severe sepsis and septic shock: a retrospective before-after study. Chest 2017;151(6):1229–1238. DOI: 10.1016/j.chest.2016.11.036
  16. Fujii T, Luethi N, Young PJ, et al. Effect of vitamin C, hydrocortisone, and thiamine vs hydrocortisone alone on time alive and free of vasopressor support among patients with septic shock: the VITAMINS randomized clinical trial. JAMA 2020;323(5):423–431. DOI: 10.1001/jama.2019.22176
  17. Sakr Y, Rubatto Birri PN, Kotfis K, et al. Higher fluid balance increases the risk of death from sepsis: results from a large international audit. Crit Care Med 2017;45(3):386–394. DOI: 10.1097/CCM.0000000000002189
  18. Zhang L, Xu F, Li S, et al. Influence of fluid balance on the prognosis of patients with sepsis. BMC Anesthesiol 2021;21(1):269. DOI: 10.1186/s12871-021-01489-1
  19. Wacker DA, Burton SL, Berger JP, et al. Evaluating vitamin C in septic shock: a randomized controlled trial of vitamin c monotherapy. Crit Care Med 2022;50(5):e458–e467. DOI: 10.1097/CCM.0000000000005427
  20. Fowler AA 3rd, Truwit JD, Hite RD, et al. 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. JAMA 2019;322(13):1261–1270. DOI: 10.1001/jama.2019.11825
  21. Sevransky JE, Rothman RE, Hager DN, et al. Effect of vitamin C, thiamine, and hydrocortisone on ventilator-and vasopressor-free days in patients with sepsis: the VICTAS randomized clinical trial. JAMAJAMA 2021;325(8):742–750. DOI: 10.1001/jama.2020.24505 Erratum in: 2021;326(11):1072.
  22. Masse MH, Ménard J, Sprague S, et al. Lessening organ dysfunction with vitamin C (LOVIT): protocol for a randomized controlled trial. Trials 2020;21(1):42. DOI: 10.1186/s13063-019-3834-1
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