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

Ari Moskowitz, Lars W Andersen, David T Huang, Katherine M Berg, Anne V Grossestreuer, Paul E Marik, Robert L Sherwin, Peter C Hou, Lance B Becker, Michael N Cocchi, Pratik Doshi, Jonathan Gong, Ayan Sen, Michael W Donnino, Ari Moskowitz, Lars W Andersen, David T Huang, Katherine M Berg, Anne V Grossestreuer, Paul E Marik, Robert L Sherwin, Peter C Hou, Lance B Becker, Michael N Cocchi, Pratik Doshi, Jonathan Gong, Ayan Sen, Michael W Donnino

Abstract

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.

Conflict of interest statement

Ethics approval and consent to participate

Not applicable.

Consent for publication

Not applicable.

Competing interests

The authors are currently conducting the Ascorbic Acid, Corticosteroids, and Thiamine in Sepsis (ACTS) clinical trial.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Suggested mechanisms for the efficacy of thiamine, ascorbic acid, and corticosteroids in sepsis. PDH pyruvate dehydrogenase, ATP adenosine triphosphate, NADPH nicotinamide adenine dinucleotide phosphate, PP2A protein phosphatase 2, ROS reactive oxygen species, BH4 tetrahydrobiopterin, ICAM intracellular adhesion molecule. A circled minus sign indicates an inhibitory action; arrows indicate an activating action; green-outlined boxes indicate a beneficial effect of the medication combination; red-outlined boxes indicate a potentially harmful effect attenuated by the medication combination

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