The Effect of Thiamine and Vitamin C Combination on Mortality Rate of Patients with Severe Sepsis: A Randomized Control Clinical Trial Study

Document Type : Original Article (s)

Authors

1 Assistant Professor, Infectious Diseases and Tropical Medicine Research Center, Isfahan University of Medical Sciences, Isfahan, Iran

2 Professor, Department of Clinical Pharmacy and Pharmacy Practice, Isfahan University of Medical Sciences, Isfahan, Iran

3 Resident, Department of Infectious Diseases and Tropical Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

4 Professor, Department of Infectious Diseases and Tropical Medicine, School of Medicine, Nosocomial Infection Research Center, Isfahan University of Medical Sciences, Isfahan, Iran

Abstract

Background: Sepsis is a potentially life-threatening condition characterized by the body's deregulated response to infection, in turn causing injury to its own tissues and organs. The present study investigated the effect of co-administration of thiamine and vitamin C on reducing mortality in patients with severe sepsis.
Methods: In this randomized clinical trial study, 86 patients with severe sepsis were assigned to treatment and control groups, each comprising 43 patients. The treatment group received thiamine 600 mg orally every
12 hours and vitamin C at a dose of 50 mg / kg, intravenously daily for 96 hours alongside standard treatment and the control group received standard treatment. Therapeutic outcome (recovery or death), duration of hospitalization and duration of ventilator connection were recorded for patients in both groups. Also, procalcitonin level (PCT) and CRP levels were measured and recorded at the beginning and after 96 hours.
Findings: The odds ratio of death outcome in the treatment group was significantly lower than the control group (0.913-0.116: 95% CI, P = 0.033, OR = 0.32). The mean length of hospital stay in the treatment group was about 7 days that was less than the control group significantly. The mean length of ICU hospitalization in the treatment group was less than the control group significantly too.
Conclusion: Co-administration of vitamin C and thiamine in sepsis patients can reduce the length of hospital stay in the intensive care unit and hospital and also reduce the serum level of inflammatory factors and reduce the rate of death in these patients.

Keywords


  1. Cui N, Zhang H, Chen Z, Yu Z. Prognostic significance of PCT and CRP evaluation for adult ICU patients with sepsis and septic shock: retrospective analysis of 59 cases. J Int Med Res 2019; 47(4): 1573-9.
  2. Martin GS, Mannino DM, Eaton S, Moss M. The epidemiology of sepsis in the United States from 1979 through 2000. N Engl J Med 2003; 348(16): 1546-54.
  3. Annane D, Bellissant E, Cavaillon JM. Septic shock. Lancet 2005; 365(9453): 63-78.
  4. Nunnally ME, Patel A. Sepsis-what's new in 2019? Curr Opin Anaesthesiol 2019; 32(2): 163-8.
  5. Yousefi H, Nahidian M, Sabouhi F. Reviewing the effects of an educational program about sepsis care on knowledge, attitude, and practice of nurses in intensive care units. Iran J Nurs Midwifery Res 2012; 17(2 Suppl 1): S91-5.
  6. Adhikari NK, Fowler RA, Bhagwanjee S, Rubenfeld GD. Critical care and the global burden of critical illness in adults. Lancet 2010; 376(9749): 1339-46.
  7. Zhao HY, Gu J, Lyu J, Liu D, Wang YT, Liu F, et al. Pharmacokinetic and pharmacodynamic efficacies of continuous versus intermittent administration of meropenem in patients with severe sepsis and septic shock: a prospective randomized pilot study. Chin Med J (Engl) 2017; 130(10): 1139-45.
  8. Yende S, Austin S, Rhodes A, Finfer S, Opal S, Thompson T, et al. Long-term quality of life among survivors of severe sepsis: analyses of two inter national trials. Crit Care Med 2016; 44(8): 1461-7.
  9. Angus DC, Van der Poll T. Severe sepsis and septic shock. N Engl J Med 2013; 369(9): 840-51.
  10. Artenstein AW, Higgins TL, Opal SM. Sepsis and scientific revolutions. Crit Care Med 2013; 41(12): 2770-2.
  11. Marik PE. Vitamin C for the treatment of sepsis: the scientific rationale. Pharmacol Ther 2018; 189: 63-70.
  12. Hwang SY, Park JE, Jo IJ, Kim S, Chung SP, Kong T, et al. Combination therapy of vitamin C and thiamine for septic shock in a multicentre, double-blind, randomized, controlled study (ATESS): study protocol for a randomized controlled trial. Trials 2019; 20(1): 420.
  13. Fowler 3rd AA, 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(1): 32.
  14. Bennett JE, Dolin R, Blaser MJ. Mandell, Douglas, and Bennetts principles and practice of infectious diseases. 9th Amsterdam, The Netherlands: Elsevier; 2019. p. 991-2.
  15. Costa NA, Gut AL, de Souza Dorna M, Pimentel JAC, Cozzolino SMF, Azevedo PS, et al. Serum thiamine concentration and oxidative stress as predictors of mortality in patients with septic shock.
    J Crit Care 2014; 29(2): 249-52.
  16. Marik PE. Patterns of death in patients with sepsis and the Use of hydrocortisone, ascorbic acid, and thiamine to prevent these deaths. Surg Infect (Larchmt) 2018; 19(8): 812-20.
  17. de Andrade JAA, Gayer CRM, de Almeida Nogueira NP, Paes MC, Bastos VLF, da Cunha Bastos Neto J, et al. The effect of thiamine deficiency on inflammation, oxidative stress and cellular migration in an experimental model of sepsis. J Inflamm (Lond) 2014; 11: 11.
  18. 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.
  19. Donnino MW, Andersen LW, Chase M, Berg KM, Tidswell M, Giberson T, et al. Randomized, double-blind, placebo-controlled trial of thiamine as a metabolic resuscitator in septic shock: a pilot study. Crit Care Med 2016; 44(2): 360-7.
  20. Jackson R, Teece S. Best evidence topic report. Oral or intravenous thiamine in the emergency department. Emerg Med J 2004; 21(4): 501-2.
  21. Manzanares W, Hardy G. Thiamine supplementation in the critically ill. Curr Opin Clin Nutr Metab Care 2011; 14(6): 610-7.
  22. Iglesias J, Vassallo AV, Patel VV, Sullivan JB, Cavanaugh J, Elbaga Y. Outcomes of metabolic resuscitation using ascorbic acid, thiamine, and glucocorticoids in the early treatment of sepsis: The ORANGES trial. Chest 2020; 158(1): 164-73.
  23. 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.
  24. Mortensen A, Lykkesfeldt J. Does vitamin C enhance nitric oxide bioavailability in a tetrahydrobiopterin-dependent manner? In vitro, in vivo and clinical studies. Nitric Oxide 2014; 36: 51-7.
  25. Oudemans-van Straaten HM, Spoelstra-de Man AM, de Waard MC. Vitamin C revisited. Crit Care 2014; 18(4): 460.
  26. Victor VV, Guayerbas N, Puerto M, Medina S, De la Fuente M. Ascorbic acid modulates in vitro the function of macrophages from mice with endotoxic Immunopharmacology 2000; 46(1): 89-101.
  27. 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.