Ascorbic acid, corticosteroids, and thiamine in sepsis: a review of the biologic rationale and the present state of clinical evaluation

Crit Care. 2018 Oct 29;22(1):283. doi: 10.1186/s13054-018-2217-4.


The combination of thiamine, ascorbic acid, and hydrocortisone has recently emerged as a potential adjunctive therapy to antibiotics, infectious source control, and supportive care for patients with sepsis and septic shock. In the present manuscript, we provide a comprehensive review of the pathophysiologic basis and supporting research for each element of the thiamine, ascorbic acid, and hydrocortisone drug combination in sepsis. In addition, we describe potential areas of synergy between these therapies and discuss the strengths/weaknesses of the two studies to date which have evaluated the drug combination in patients with severe infection. Finally, we describe the current state of current clinical practice as it relates to the thiamine, ascorbic acid, and hydrocortisone combination and present an overview of the randomized, placebo-controlled, multi-center Ascorbic acid, Corticosteroids, and Thiamine in Sepsis (ACTS) trial and other planned/ongoing randomized clinical trials.

Keywords: Ascorbic acid; Corticosteroids; Metabolic resuscitation; Sepsis; Thiamine.

Publication types

  • Review

MeSH terms

  • Adrenal Cortex Hormones / pharmacology
  • Adrenal Cortex Hormones / therapeutic use*
  • Anti-Bacterial Agents / adverse effects
  • Anti-Bacterial Agents / therapeutic use
  • Ascorbic Acid / pharmacology
  • Ascorbic Acid / therapeutic use*
  • Drug Therapy, Combination / methods
  • Drug Therapy, Combination / standards
  • Humans
  • Hydrocortisone / pharmacology
  • Hydrocortisone / therapeutic use
  • Models, Biological
  • Sepsis / drug therapy*
  • Thiamine / pharmacology
  • Thiamine / therapeutic use*


  • Adrenal Cortex Hormones
  • Anti-Bacterial Agents
  • Ascorbic Acid
  • Hydrocortisone
  • Thiamine