Insights Into Thiamine Supplementation in Patients With Septic Shock

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.

Association of thiamine administration and prognosis in critically ill patients with heart failure

“…Nutritional supplementation is economical and safe and, if proven effective, can significantly reduce the burden of heart failure. Thiamine supplementation can improve the state of heart failure caused by severe thiamine deficiency, but whether thiamine supplementation is effective in critically ill patients with heart failure remains unknown ( Costa et al, 2022 ). Therefore, this study aimed to explore the correlation between thiamine use and prognosis in patients with HF.…”

Thiamine and benfotiamine: Focus on their therapeutic potential

“…In a study in a rat model of acute ethanol exposure, thiamine was found to increase glutathione levels and reduce liver inflammation [ 37 ]. In a study in a mouse model of sepsis, thiamine was found to reduce the production of pro-inflammatory cytokines and improve survival [ 38 ].…”

Metabolic failure due to thiamine deficiency during critical illness

“…Persistent elevated lactate levels at 24-h demonstrate a strong prognostic value for in-hospital death among adult patients diagnosed with septic shock. The collective action of these mechanisms plays a role in the occurrence and/or exacerbation of thiamine deficiency in individuals diagnosed with septic shock [3].…”