Insights Into Thiamine Supplementation in Patients With Septic Shock.

Nara Aline Costa,Amanda Gomes Pereira,Leonardo Antonio Mamede Zornoff,Leonardo Rufino Garcia,Clara Sandra Araujo Sugizaki,Bertha Furlan Polegato,Nayane Maria Vieira,Paula Schmidt Azevedo,Sérgio Alberto Rupp De Paiva,Marcos Ferreira Minicucci

doi:10.3389/fmed.2021.805199

Nara Aline Costa, Amanda Gomes Pereira + Show 8 more

Open Access

https://doi.org/10.3389/fmed.2021.805199

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Abstract

Septic shock is associated with unacceptably high mortality rates, mainly in developing countries. New adjunctive therapies have been explored to reduce global mortality related to sepsis. Considering that metabolic changes, mitochondrial dysfunction and increased oxidative stress are specific disorders within the path of septic shock, several micronutrients that could act in cellular homeostasis have been studied in recent decades. Thiamine, also known as vitamin B1, plays critical roles in several biological processes, including the metabolism of glucose, synthesis of nucleic acids and reduction of oxidative stress. Thiamine deficiency could affect up to 70% of critically ill patients, and thiamine supplementation appears to increase lactate clearance and decrease the vasopressor dose. However, there is no evident improvement in the survival of septic patients. Other micronutrients such as vitamin C and D, selenium and zinc have been tested in the same context but have not been shown to improve the outcomes of these patients. Some problems related to the neutrality of these clinical trials are the study design, doses, route, timing, length of intervention and the choice of endpoints. Recently, the concept that multi-micronutrient administration may be better than single-micronutrient administration has gained strength. In general, clinical trials consider the administration of a single micronutrient as a drug. However, the antioxidant defense is a complex system of endogenous agents in which micronutrients act as cofactors, and the physiological interactions between micronutrients are little discussed. In this context, the association of thiamine, vitamin C and corticoids was tested as an adjunctive therapy in septic shock resulting in a significant decrease in mortality. However, after these initial results, no other study conducted with this combination could reproduce those benefits. In addition, the use of low-dose corticosteroids is recommended in patients with septic shock who do not respond to vasopressors, which can affect the action of thiamine. Therefore, given the excellent safety profile, good biologic rationale and promising clinical studies, this review aims to discuss the mechanisms behind and the evidence for single or combined thiamine supplementation improving the prognosis of patients with septic shock.

Highlights

Septic shock is a subset of sepsis characterized by profound hemodynamic alterations associated with organ dysfunction and is one of the most common causes of admission to intensive care units (ICUs) [1]
This review aims to discuss the mechanisms and the evidence for single or combined thiamine supplementation on the prognosis of patients with septic shock
Thiamine deficiency not evaluated The median time from hospital admission to thiamine administration was 6.4 hours Thiamine administration was associated with improved lactate clearance and a reduction in 28-day mortality There were no differences in any other secondary outcomes

Summary

Introduction

Septic shock is a subset of sepsis characterized by profound hemodynamic alterations associated with organ dysfunction and is one of the most common causes of admission to intensive care units (ICUs) [1]. Most notably in sepsis, the metabolic response to trauma, necessary, can usually overwhelm the body’s metabolism, leading to a wide range of clinical consequences. This response implies significant changes in intermediary metabolism, including increased glycogenolysis, inhibition of glycogenesis and increased lipolysis, producing glucose via gluconeogenesis of lactate, glycerol and amino acids [3]. In this scenario, some vitamins and minerals are essential for energy metabolism and mitochondrial function; among these, thiamine deserves to be highlighted [4, 5]. Thiamine deficiency might be involved in the pathophysiology of septic shock because high serum lactate concentrations, metabolic acidosis and hypotension can occur in both conditions [6] (Figure 1)

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