Do Not Forget To Give Thiamine To Your Septic Shock Patient!

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  1. paymanz

    paymanz Member

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    Do not forget to give thiamine to your septic shock patient!

    Thiamine was the first B vitamin to be identified and is also referred to as vitamin B1. It is a water-soluble vitamin that is an indispensable constituent of cellular metabolism (1). A lack of this vitamin can, therefore, be potentially life-threatening (2). Thiamine is present in the human body as free thiamine and as various phosphorylated forms: thiamine monophosphate, thiamine diphosphate, also known as thiamine pyrophosphate (TPP) (3,4), which is the most important and active form of this vitamin, and thiamine triphosphate. Thiamin pyrophosphate is an intracellular compound, which is why it can be considered as the best marker of thiamine nutritional status (1,4). It acts in concomitance with magnesium to expedite various mitochondrial oxidative decarboxylation reactions (Figure 1). Thiamin pyrophosphate is necessary as a cofactor for branched-chain ketoacid dehydrogenase complex essential for the metabolism of the branched-chain amino acids and for two critical complexes required for the mitochondrial synthesis of adenosine triphosphate (ATP): pyruvate and 2-oxoglutarate dehydrogenase (α-ketoglutarate) complexes. Specifically, TPP is a catalyst in the reactions of pyruvate to acetyl-Coenzyme A and α-ketoglutarate to succinyl-Coenzyme A in the Krebs cycle (Figure 1). Also, TPP serves as a coenzyme for transketolase, a cytosolic enzyme implicated in the pentose phosphate pathway, that functions in maintaining cell redox status through the production of NADPH (reduced nicotinamide adenine dinucleotide phosphate) and glutathione (5,6) (Figure 1). Thus, thiamine is an essential source of energy generation from glucose, via the conversion of pyruvate from glucose into acetyl-Coenzyme A for access to the tricarboxylic acid cycle (6), and lack of thiamine leads to alterations in intermediate metabolism that end-up in lactic acidosis (4).

    Increased lactate levels in septic shock may result from different mechanisms. Inadequacy between oxygen delivery and oxygen demand by the tissues, impairment of tissue oxygen extraction due to the sepsis-induced alterations in the microcirculation, and mitochondrial dysfunction all lead to the activation of anaerobic metabolism, and pyruvate is shunted toward lactate production (20). Other non-hypoxic mechanisms such as accelerated aerobic glycolysis induced by sepsis-associated inflammation (20), increased Na+-K+-ATPase activity through β2 stimulation (21), sepsis-induced inhibition of pyruvate dehydrogenase complex (22), impaired lactate clearance (23), and may be thiamine deficiency (18) may contribute to hyperlactatemia in septic shock patients. However, the source of lactic acidosis in septic shock patients is not usually identified by ICU physicians at the bedside. Also, in practice, measurements of plasma thiamine levels are not widely available laboratory tests and take several days to perform and, therefore, will not aid in decision making in septic shock. Nevertheless, septic shock can have manifestations similar to Shoshin beriberi and as adverse effects of thiamine administration are uncommon at both low or high dose and the overall safety profile (10), we think that septic shock patients should be given thiamine parenterally without waiting for the results of thiamine level. The European Society for Clinical Nutrition and Metabolism guidelines for parenteral nutrition in intensive care recommended thiamine supplementation of 100 to 300 mg/day during the first three days in the ICU for all patients with suspected thiamine deficiency (24). However, a dosage upwards to 500 mg may be necessary for patients with septic shock. Because anaphylaxis has been reported in rare instances (10), guidelines in the United Kingdom have recommended that thiamine should be administered over 15- to 30-minute interval in a mixture of saline solution or dextrose, with the intention of averting potential adverse reactions.

    In conclusion, the authors should be congratulated for this fascinating and original study that shed the light on the possible beneficial effects of thiamine treatment in septic shock patients.
     
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