Research Article
Volume 4 Issue 6 - 2020
The Effect of Using Vitamin C, Hydrocortisone and Thiamine Triple Therapy in the Treatment of Septic Shock - A Randomized Clinical Trial - Pilot Study
Reza Ronaghi1*, Kelly Fan1,2, Jordan Rees1, Patrick Baghdasaryan1, Jenny Tang1, Adrienne Quinn1, Samantha Spieling3, May Lee1 and Ahmet Baydur1
1Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, Keck School of Medicine, University of Southern California, USA
2Scripps Health, La Jolla, CA, USA
3Scripps Whittier Diabetes Institute, Scripps Health, La Jolla, CA, USA
*Corresponding Author: Reza Ronaghi, Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, Keck School of Medicine, University of Southern California, USA.
Received: April 19, 2020; Published: May 25, 2020


Introduction: Sepsis is a clinical syndrome with physiologic and biochemical derangements caused by a dysregulated inflammatory response to infection. A recent retrospective study demonstrated that vitamin C, hydrocortisone and thiamine in intensive care unit (ICU) patients with septic shock, when added to standard care, improved mortality and outcomes.

Methods: This prospective single-blinded study evaluated the effects of addition of triple therapy to standard ICU care on 28-day mortality in patients with septic shock defined as sepsis-induced hypotension requiring vasopressors with serum lactate level > 2 mmol/L. Patients were randomized to receive either standard ICU care (control) or standard care plus intravenous (IV) Vitamin C (1.5 gram every 6 hours) for 4 days or until ICU discharge, IV hydrocortisone (50 mg every 6 hours) for 7 days or until ICU discharge, and IV thiamine (200 mg every 12 hours) for 4 days or until ICU discharge.

Results: Analysis of 41 enrolled patients showed no significant difference at baseline between the two groups in terms of demographics or severity of septic shock. Triple therapy showed no effects on ICU length of stay, weaning from vasoactive drugs, clearance of lactic acid, preservation of renal function and weaning from ventilator support. The triple therapy group showed a trend towards increased mortality that did not reach statistical significance, but a low side-effect profile, indicating safety for use.

Interpretation: This prospective human study suggests triple therapy has limited use in the treatment of septic shock; larger studies should be pursued prior to widespread usage in septic shock.

Keywords: Intensive Care Unit (ICU); Vitamin C; Intravenous (IV); Hydrocortisone


  1. Martin GS., et al. “The epidemiology of sepsis in the United States from 1979 through 2000”. The New England Journal of Medicine 16 (2003): 1546-1554.
  2. Kaukonen KM., et al. “Mortality related to severe sepsis and septic shock among critically ill patients in Australia and New Zealand, 2000-2012”. The Journal of the American Medical Association 13 (2014): 1308-1316.
  3. Roh J., et al. “Factors predicting long term survival of patients with sepsis on arrival at the emergency department: A single center, observational study”. Medicine33 (2019): e16871.
  4. Rangel-Frausto MS., et al. “The natural history of the systemic inflammatory response syndrome (SIRS). A prospective study”. The Journal of the American Medical Association 2 (1955): 117-123.
  5. Singer M., et al. “The third international consensus definitions for sepsis and septic shock (Sepsis-3)”. The Journal of the American Medical Association 8 (2016): 801-810.
  6. Donnino MW., et al. “Randomized, Double-Blind, Placebo-Controlled Trial of Thiamine as a Metabolic Resuscitator in Septic Shock: A Pilot Study”. Critical Care Medicine 2 (2016): 360-367.
  7. Kadri SS., et al. “Estimating ten-year trends in septic shock incidence and mortality in United States academic medical centers using clinical data”. Chest2 (2017): 278-285.
  8. Rowan KM., et al. “Early, Goal-directed therapy for septic shock - A Patient-Level Meta-Analysis”. The New England Journal of Medicine 23 (2017): 2223-2234.
  9. Arternstein AW., et al. “Sepsis and scientific revolutions”. Critical Care Medicine 12 (2013): 2770-2772.
  10. Marik PE., et al. “Hydrocortisone, vitamin C, and thiamine for the treatment of severe sepsis and septic shock: a retrospective before-after study”. Chest6 (2017): 1229-1238.
  11. Carr AC., et al. “Ascorbate-dependent vasopressor synthesis: a rationale for vitamin C administration in severe sepsis and septic shock?” Critical Care 19 (2015): 418.
  12. Wilson JX. “Evaluation of vitamin C for adjuvant sepsis therapy”. Antioxidants and Redox Signaling 17 (2013): 2129-2140.
  13. Wilson JX. “Mechanism of action of vitamin C in sepsis: ascorbate modulates redox signaling in endothelium”. Biofactors 1 (2009): 5-13.
  14. Manning J., et al. “Vitamin C promotes maturation of T-Cells”. Antioxidants and Redox Signaling 17 (2013): 2054-2067.
  15. Fowler AA., et al. “Phase I safety trial of intravenous ascorbic acid in patients with severe sepsis”. Journal of Translational Medicine 12 (2004): 32.
  16. Zabet MH., et al. “Effect of high‐dose ascorbic acid on vasopressor’s requirement in septic shock”. Journal of Research in Pharmacy Practice 2 (2016): 94-100.
  17. Sprung CL., et al. “Hydrocortisone therapy for patients with septic shock”. The New England Journal of Medicine 2 (2008): 111-124.
  18. Keh D., et al. “Effect of hydrocortisone on development of shock among patients with severe sepsis: The HYPRESS Randomized Clinical Trial”. The Journal of the American Medical Association 17 (2016): 1775-1785.
  19. Barabutis N., et al. “Hydrocortisone and ascorbic acid synergistically prevent and repair lipopolysaccharide-induced pulmonary endothelial barrier Dysfunction”. Chest (2017): S0012-3692.
  20. Manzanares W and Hardy G. “Thiamine supplementation in the critically ill”. Current Opinion in Clinical Nutrition and Metabolic Care 6 (2011): 610-617.
  21. Donnino MW., et al. “Randomized, double-blind, placebo-controlled trial of thiamine as a metabolic resuscitator in septic shock: a pilot study”. Critical Care Medicine 2 (2016): 360-367.
  22. Singer M., et al. “The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3)”. The Journal of the American Medical Association 8 (2016): 801-810.
  23. Fink MP and Warren HS. “Strategies to improve drug development for sepsis”. Nature Reviews Drug Discovery 10 (2014): 741-758.
  24. Ferraro PM., et al. “Total, dietary, and supplemental vitamin C intake and risk of incident kidney stones”. American Journal of Kidney Diseases (2017).
  25. Prier M., et al. “No reported renal stones in intravenous Vitamin C Administration: A prospective case series study”. Antioxidants 95 (2018): 68.
Citation: Reza Ronaghi., et al. “The Effect of Using Vitamin C, Hydrocortisone and Thiamine Triple Therapy in the Treatment of Septic Shock - A Randomized Clinical Trial - Pilot Study”. EC Emergency Medicine and Critical Care 4.6 (2020): 109-118.

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