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Thiamine (vitamin B1) in septic shock: a targeted therapy.

ABSTRACT: Thiamine (vitamin B1) is a water-soluble vitamin essential for human health. Thiamine deficiency is causal and/or contributory in a number of debilitating diseases including beri-beri, the Wernicke-Korsakoff syndrome, optic neuropathy, and others. While thiamine deficiency is relatively rare in developed nations as a result of dietary supplementation, thiamine deficiency is more common in nutritionally compromised populations. Thiamine pyrophosphate, a thiamine derivative, is essential to the citric acid cycle and thiamine deficiency can result in impaired aerobic respiration and cellular energy production. Thiamine also plays an important role in the pentose phosphate pathway and other key metabolic processes. Although thiamine deficiency is a known cause of lactic acidosis, it has been recently evaluated as a potential contributor to refractory lactic acidosis and organ injury in septic shock and other shock states. In this article, we review the epidemiology of thiamine deficiency in septic shock and the existing evidence base supporting thiamine supplementation. We conclude that specific sepsis phenotypes may stand to benefit the most from thiamine supplementation, and efforts might be made to identify and supplement these patients early in their hospital course.

SUBMITTER: Moskowitz A

PROVIDER: S-EPMC7024754 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Thiamine (vitamin B1) in septic shock: a targeted therapy.

Moskowitz Ari A Donnino Michael W MW

Journal of thoracic disease 20200201 Suppl 1

Thiamine (vitamin B1) is a water-soluble vitamin essential for human health. Thiamine deficiency is causal and/or contributory in a number of debilitating diseases including beri-beri, the Wernicke-Korsakoff syndrome, optic neuropathy, and others. While thiamine deficiency is relatively rare in developed nations as a result of dietary supplementation, thiamine deficiency is more common in nutritionally compromised populations. Thiamine pyrophosphate, a thiamine derivative, is essential to the ci ...[more]

PMID: 32148929

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Project description:BackgroundThe objective of this study was to evaluate the clinical efficacy of thiamine and vitamin C with or without hydrocortisone coadministration on the treatment of sepsis and septic shock.MethodsMEDLINE, EMBASE and CENTRAL databases were searched for randomized controlled trials (RCTs) that made a comparative study between the combination therapy of vitamin C and thiamine with or without hydrocortisone and the administration of placebo in patients with sepsis or septic shock. Two reviewers independently performed study selection, data extraction and quality assessment. Both short-term mortality and change in the sequential organ failure assessment (SOFA) score from baseline (delta SOFA) were set as the primary outcomes. Secondary endpoints included intensive care unit (ICU) mortality, new onset of acute kidney injury, total adverse events, ICU and hospital length of stay, duration of vasopressor usage and ventilator-free days. Meanwhile, trial sequential analysis was conducted for primary outcomes.ResultsEight RCTs with 1428 patients were included in the current study. The results showed no significant reduction of short-term mortality in sepsis and septic shock patients who received combination therapy of vitamin C and thiamine with or without hydrocortisone compared to those with placebo {risk ratio (RR), 1.02 [95% confidence interval (CI), 0.87 to 1.20], p = 0.81, I 2 = 0%; risk difference (RD), 0 [95% CI, -0.04 to 0.05]}. Nevertheless, the combination therapy was associated with significant reduction in SOFA score [mean difference (MD), -0.63, (95% CI, -0.96 to -0.29, p < 0.001, I 2 = 0%] and vasopressors duration (MD, -22.11 [95% CI, -30.46 to -13.77], p < 0.001, I 2 = 6%). Additionally, there were no statistical differences in the pooled estimate for other outcomes.ConclusionsIn the current meta-analysis, the combination therapy of vitamin C and thiamine, with or without hydrocortisone had no impact on short-term mortality when compared with placebo, but was associated with significant reduction in SOFA score among patients with sepsis and septic shock.

Project description:BackgroundThe combination therapy of hydrocortisone, vitamin C, and thiamine has been proposed as a potential treatment in patients with sepsis and septic shock. However, subsequent trials have reported conflicting results in relation to survival outcomes. Hence, we performed this randomized controlled trial (RCT) to evaluate the efficacy and safety of early combination therapy among adult patients with septic shock.MethodsThis single-center, double-blind RCT enrolled adult patients with diagnosis of septic shock within 12 h from Northern Jiangsu People's Hospital between February 2019 and June 2021. Recruited patients were randomized 1:1 to receive intervention (hydrocortisone 200 mg daily, vitamin C 2 g every 6 h, and thiamine 200 mg every 12 h) or placebo (0.9% saline) for 5 days or until ICU discharge. The primary endpoint was 90-day mortality. The secondary endpoints included mortality at day 28, ICU discharge, and hospital discharge; shock reversal; 72-h Delta SOFA score; ICU-free days, vasopressor-free days, and ventilator support -free days up to day 28; ICU length of stay (LOS) and hospital LOS.ResultsAmong 426 patients randomized, a total of 408 patients with septic shock were included in the per-protocol (PP) analysis, of which 203 were assigned to the intervention group and 205 to the placebo group. In the PP population, the primary outcome of 90-day mortality was 39.9% (81/203) and 39.0% (80/205) in the intervention and the placebo groups, respectively, and was not significantly different (P = 0.86). There was no significant difference between two groups in 28-day mortality (36.5% vs. 36.1%, P = 0.94) or the ICU mortality (31.5% vs. 28.8%, P = 0.55) and hospital mortality (34.5% vs. 33.2%, P = 0.78). No other secondary outcomes showed significant differences between two groups, including shock reversal, vasopressor-free days, and ICU LOS. Intention-to-treat analysis included all the 426 patients and confirmed these results (all P > 0.05).ConclusionAmong adult patients with septic shock, early use of hydrocortisone, vitamin C, and thiamine combination therapy compared with placebo did not confer survival benefits. Trial registration ClinicalTrials.gov: NCT03872011 , registration date: March 12, 2019.

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Thiamine (vitamin B1) in septic shock: a targeted therapy.

Publications

Thiamine (vitamin B1) in septic shock: a targeted therapy.

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