The effect of parenteral selenium on outcomes of mechanically ventilated patients following sepsis: a prospective randomized clinical trial
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BACKGROUND: Sepsis and septic shock is characterized by oxidative stress that mainly promotes systemic inflammation and organ failure due to excessive free radical production and depletion of antioxidant defenses. Therefore, we investigated the effect of selenium administration on antioxidant status, levels of cytokines and clinical outcomes. METHODOLOGY: This study was a prospective randomized control trial (RCT) whereby patients received selenium as sodium selenite (2 mg IV bolus followed by 1.5 mg continuous infusion for 14 days) plus standard therapy. The control group received standard therapy without selenium. The primary endpoint was 28-day mortality. The changes in the mean levels of glutathione peroxidase (GPX) activity, IL-6, IL-8 and IL-10, the incidence of ventilator-associated pneumonia (VAP) and other secondary endpoints were also recorded. VAP was broken down into early VAP and late VAP to see the clinical significance of each. We also recorded any adverse outcomes from selenium infusion. RESULTS: Over 24-month period, 54 patients were recruited and randomized and an intention to treat (ITT) principle was applied (selenium, n = 29; control, n = 25) in the final analysis. There was no statistically significant difference between the two groups in 28-day mortality although it was lower in the selenium group compared with the control group: 9 (31 %) in the selenium versus 10 (40 %) in the control groups (p = 0.49). At day 0, GPX activity was 0.185 ± 0.3 versus 0.19 ± 0.3 U/mL (p = 0.9), day 3, GPX activity was 0.52 ± 0.5 versus 0.17 ± 0.2 U/mL (p = 0.02), at day 7 it was 0.55 ± 0.5 versus 0.24 ± 0.3 U/mL (p = 0.032), at day 10 it was 0.62 ± 0.7 versus 0.33 ± 0.4 U/mL (p = 0.048) and at day 14 it was 1.1 ± 1 versus 0.89 ± 1 U/mL (p = 0.70) for the selenium versus control groups, respectively. However, there were no significant differences between the mean plasma levels of all the three inflammatory cytokines at any point in time between the two groups. There was a significant reduction in occurrence of VAP in the selenium group compared with the control group (55.2 versus 84 %, p = 0.023), respectively. CONCLUSION: High-dose selenium administration within the time frame of early goal-directed therapy was not resulted in reduction of 28-day mortality, but increased the activity of glutathione peroxidase with no effect on the levels of inflammatory cytokines at any point in time in mechanically ventilated septic patients. However, selenium supplementation in mechanically ventilated patients following sepsis was associated with reduced occurrence of VAP. TRIAL REGISTRATION: IRCT201212082887N4 at WHO Clinical Trial Registry, August 29, 2014.
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Subsequent RCTs investigating high-dose parenteral selenium administration in septic patients showed no beneficial effect on mortality.
“Subsequent RCTs investigating high-dose parenteral selenium administration in septic patients showed no beneficial effect on mortality [75,76].”
From Nutrition in Sepsis: A Bench-to-Bedside Review. (2020) · cites this paper as [75]
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- Authors
- Chelkeba, L., Ahmadi, A., Abdollahi, M., Najafi, A., Ghadimi, M. H., Mosaed, R., & Mojtahedzadeh, M.
- Affiliations
- Jimma University (ET)
- Sina Hospital (IR)
- Pharmaceutical Sciences Research Center (IR)
- Corresponding author
- Mojtahedzadeh, Mojtaba
- ORCID
- Venue
- Annals of Intensive Care
- Publisher
- Elsevier BV
- Published
- 2015
- Volume
- 5
- Issue
- 1
- Pages
- 29
- ISSN
- 2110-5820 (ISSN-L)
- PMC
- PMC4591221
- OpenAlex
- W2114815291
- Cited by
- 51
- References
- 57
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 4 · 2023: 5 · 2022: 7 · 2021: 9 · 2020: 3 · 2019: 5 · 2018: 3 · 2017: 7 · 2016: 3
- FWCI
- 3.40
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Annals of Intensive Care (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Tehran University of Medical Sciences and Health Services
- Topics
- Health Sciences › Medicine › Epidemiology › Sepsis Diagnosis and Treatment
- Health Sciences › Nursing › Nutrition and Dietetics › Selenium in Biological Systems
- Health Sciences › Nursing › Nutrition and Dietetics › Clinical Nutrition and Gastroenterology
- Keywords
- selenium supplementation, sodium selenite, sepsis, septic shock, mechanical ventilation, oxidative stress, antioxidant status, glutathione peroxidase, cytokines, interleukin-6, interleukin-8, IL-10, ventilator-associated pneumonia, 28-day mortality, organ failure, systemic inflammation, free radicals
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