Original ContributionSelenium supplementation for sepsis: a meta-analysis of randomized controlled trials☆,☆☆
Introduction
Although antibiotics and various supportive therapies are constantly being developed, sepsis remains one of the major factors that cause death in critically ill patients [1]. The pathogenesis of sepsis involves microbial infection, inflammation, and immune disorders [2]. Moreover, oxidative stress resulting from excessive reactive oxygen species production is associated with multi-organ failure in septic patients [3].
Selenium is vital for human health because of its involvement in selenocysteine and subsequent selenoprotein synthesis. It plays a key role in activating the bioactivity of selenoprotein. The most important selenoprotein is glutathione peroxidase (GSH-Px), which eliminates lipid hydroperoxides and hydrogen peroxide to reduce bio-membrane damage from excessive oxidative stress [4], [5], [6], [7], [8], [9], [10]. In septic patients, plasma GSH-Px concentration and activity are decreased [11], [12], [13], [14], [15], [16]. Selenium also has an effect on the immune system. Selenium supplementation inhibited IL-6 secretion through the inhibition of nuclear factor κB via GSH-Px and promoted the proliferation and activity of T cells and natural killer cells in vivo [17], [18]. In addition, selenium is closely related to the endocrine system. Lodothyronine deiodinase enzyme, another type of selenoprotein, converts thyroxine (T4) into triiodothyronine (T3), and low T3 might point to adverse outcome in septic patients [19].
It was hypothesized that selenium supplementation might be beneficial in sepsis through the induction of anti-oxidant selenoenzymes. Thus far, several trials have been performed to investigate the effect of selenium supplementation in septic patients. However, no consistent conclusion was made. Therefore, we attempted to systematically summarize the available randomized controlled trials (RCTs) to evaluate the effect of selenium supplementation on important clinical outcomes in septic patients.
Section snippets
Methods
The present meta-analysis was conducted according to the guidelines of Preferred Reporting Items for Systematic Reviews and Meta-Analyses [20].
Study identification
The comprehensive search yielded a total of 169 relevant publications (Fig. 1). After 43 duplicate articles were eliminated, 126 were screened and 103 excluded. Of the remaining 23 studies, 18 were eliminated (one study was excluded for focusing on population of critical ill patients, two for not providing relevant outcomes, one for focusing on children, three for review articles, 2 for duplicate data, 3 for not providing sufficient information to judge their eligibility, and 6 for
Discussion
Selenium is an important nutritional element. In the past decades, many studies have demonstrated that selenium has anti-oxidative and immunoregulatory effects via the induction of selenoenzymes [28], [29]. However, whether selenium supplementation is beneficial for sepsis is controversial. The present meta-analysis showed that selenium supplementation did not reduce all-cause mortality, HAP or length of ICU stay in septic patients. In addition, no significant difference in adverse events was
Conclusions
The present meta-analysis showed that selenium supplementation did not reduce all-cause mortality, HAP, length of ICU stay, or adverse events in septic patients. Accordingly, routinely supplementing selenium at doses higher than the tolerance level (400 μg/d) is not recommended in septic patients. Considering the limited number of RCTs included, more prospective multicenter clinical trials on selenium therapy in septic patients are warranted in the future.
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2021, Journal of NutritionAntioxidant reserve of the lungs and ventilator-associated pneumonia: A clinical trial of high dose selenium in critically ill patients
2018, Journal of Critical CareCitation Excerpt :Landucci et al. in a recent meta-analysis showed that use of high-dose selenium may even have a beneficial effect on 28-day mortality in critically ill patients [13]. Huang et al., in another meta-analysis, showed that parenteral selenium supplementation reduced risk of mortality, specifically within the critically ill septic population [14], while another meta-analysis demonstrated opposing results [15]. Additionally, several studies have shown that selenium treatment can reduce oxidative stress and multi-organ failure in addition to promoting protective effects on the pulmonary system [16,17].
Role of divalent metals in infectious disease susceptibility and outcome
2018, Clinical Microbiology and InfectionCitation Excerpt :In a recent multicentre study of paediatric patients undergoing long-term care in the ICU, supplementation with selenium (in combination with zinc, glutamine and whey protein) reduced the rate of nosocomial infection and sepsis in immunocompromised patients but conferred no advantage in the prevention of infection in immunocompetent patients [95]. A number of meta-analyses [13,96–102] have evaluated the results of varying numbers of clinical trials of antioxidant micronutrients, including selenium, in critically ill adult patients. Several earlier analyses concluded that parenteral administration of selenium may be associated with a significant reduction in mortality [13,99–101] and in the duration of mechanical ventilation, with a trend towards a reduction in infections [13].
Nutrition as medical therapy
2014, Critical Care Nursing Clinics of North AmericaCitation Excerpt :Several recent meta-analyses have also resulted in discordant results. Alhazzani and colleagues13 concluded that high-dose selenium therapy may result in improved mortality, whereas Kong and colleagues14 concluded that there was no clinical benefit for selenium therapy in sepsis. Although these mixed results highlight that the clinical benefit of selenium is not conclusive, they do share 1 promising result: high-dose selenium therapy seems to be safe and well tolerated in the setting of sepsis and septic shock.
Selenium status in neonates with connatal infection
2016, British Journal of NutritionThe effect of selenium therapy in critically ill patients: an umbrella review of systematic reviews and meta-analysis of randomized controlled trials
2023, European Journal of Medical Research
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Funding: Not funded.
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Competing interests: The authors declare that they have no competing interests.
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These authors contributed equally to this study.