Effects of High-Dose Selenium on Mortality of Sepsis and Septic Shock Patients with Severe Selenium Deficiency in Taiwan

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Chun-Man Chen Yen-Ling Chen Shu-Min Lin Huang-Pin Wu Jiun-Nong Lin Kai-Huang Lin Chin-Ming Chen Kuang-Yao Yang Shih-Chi Ku Fu-Tsai Chung Chih-His Kuo Chien Tung Chiu Chi-Kuei Hsu Hsin-Hui Hsu Chien-Ming Chu Han-Chung Hu Chung-Shu Lee Shin-Hwar Wu I-Chieh Mao Ting-Yu Chao Yi-Wen Chu Du-Shieng Chien

Abstract

The relationship between serum selenium levels and mortality was investigated in septic patients with severe selenium deficiency (baseline selenium ≤ 80 ng/mL). Eligible patients of sepsis or septic shock were randomized to receive Placebo or High-Dose Selenium (1,000 μg/day) via intravenous injection. Safety, serum selenium, mortality, SOFA, and Glasgow Coma Scale (GCS) scores were monitored. Among all 330 subjects, 27.9% subjects (n=92) had severe selenium deficiency (mean serum selenium = 66.5 ng/mL). Mortality of severe selenium deficiency patients was 27.2%, significantly higher than 17.9% of all subjects. In severe selenium deficiency Placebo group (n=45), 62% subjects showed gradual increase of selenium levels to ~110 ng/mL (mortality ~21.4%), while 38% subjects remained at low selenium ≤ 110 ng/mL throughout study (mortality ~41.2%). Mortality for Placebo subjects with normal baseline selenium ≥ 110 ng/mL was 13.6%. With High-Dose Selenium treatment, 91% of severe selenium deficiency subjects showed quick selenium increase to ~110 ng/mL (mortality 25.5%). Mortality was reduced to 8.6% for High-Dose Selenium subjects with baseline selenium ≥ 110 ng/mL. The odds ratio showed significantly greater survival of High-Dose Selenium subjects with baseline selenium ≥ 110 ng/mL (91.4%) than severe selenium deficiency Placebo subjects (74.1%). Mean baseline SOFA scores for severe selenium deficiency patients were 9.1–9.4, decrease of SOFA scores in High-Dose Selenium subjects was significantly greater than Placebo subjects, along with significant improvement of GCS scores. Repeated infusion of High-Dose Selenium in severe selenium deficiency patients for 14 days was safe and well-tolerated. Mortality for patients with sepsis was clearly affected by serum selenium concentrations. High mortality (41–50%) was observed in the sepsis patients constantly with low selenium £ 80 ng/mL; mortality was reduced to 21–23% if their serum selenium could be increased to ≥ 110 ng/mL. High-Dose Selenium resulted in rapid restoration of serum selenium and improved the survival of severe selenium deficiency septic patients. Low mortality (9–14%) was observed in the sepsis patients starting with baseline selenium ≥ 110 ng/mL. Overall this study demonstrates the significant impact of insufficient selenium levels on the mortality of septic patients. Treatment with high-dose selenium reduced the mortality of severe selenium deficiency septic subjects.

Keywords: Selenium deficiency, sepsis and septic shock, mortality, SOFA score, Asian

Article Details

How to Cite
CHEN, Chun-Man et al. Effects of High-Dose Selenium on Mortality of Sepsis and Septic Shock Patients with Severe Selenium Deficiency in Taiwan. Medical Research Archives, [S.l.], v. 12, n. 2, feb. 2024. ISSN 2375-1924. Available at: <https://esmed.org/MRA/mra/article/view/5044>. Date accessed: 05 oct. 2024. doi: https://doi.org/10.18103/mra.v12i2.5044.
Section
Research Articles

References

1. Singer M, Deutschman CS, Seymour CW, et al. The third international consensus definitions for sepsis and septic shock (sepsis-3). JAMA. 2016;315(8):801-810.

2. Cohen J, Vincent JL, Adhikari NKJ, et al. Sepsis: a roadmap for future research. Lancet Infect Dis. 2015;15(5):581-614.

3. Schlapbach LJ, Kissoon N, Alhawsawi A, et al. World Sepsis Day: a global agenda to target a leading cause of morbidity and mortality. Am J Physiol Lung Cell and Mol Physiol. 2020;319(3):L518-L522.

4. Rudd KE, Johnson SC, Agesa KM, et al. Global, regional, and national sepsis incidence and mortality, 1990–2017: analysis for the Global Burden of Disease Study. The Lancet. 2020;395(10219):200-211.

5. Jarczak D, Kluge S, Nierhaus A. Sepsis—Pathophysiology and therapeutic concepts. Front Med (Lausanne). 2021;8:609.

6. Mahmoodpoor A, Faramarzi E, Reyhanifard A, et al. The effects of selenium supplementation on inflammatory markers in critically ill patients. SN Appl Sci. 2022;4 (12):326.

7. Berger MM, Chioléro RL. Antioxidant supplementation in sepsis and systemic inflammatory response syndrome. Crit Care Med. 2007;35(9).

8. Roman M, Jitaru P, Barbante C. Selenium biochemistry and its role for human health. Metallomics. 2013;6(1):25-54.

9. Manzanares W, Langlois PL, Heyland DK. Pharmaconutrition with selenium in critically ill patients. Nutrition in Clinical Practice. 2015;30(1):34-43.

10. Pfister C, Dawzcynski H, Schingale FJ. Sodium selenite and cancer related lymphedema: Biological and pharmacological effects. J of Trace Elem in Med and Biol. 2016;37:111-116.

11. Berger MM, Reymond MJ, Shenkin A, et al. Influence of slenium supplements on the post-traumatic alterations of the thyroid axis: a placebo-controlled trial. Intensive Care Med. 2001;27:91-100.

12. Stoppe C, Spillner J, Rossaint R, et al. Selenium blood concentrations in patients undergoing elective cardiac surgery and receiving perioperative sodium selenite. Nutrients. 2013;29(1):158-165.

13. Yang KH, Lee LT, Lee YS, et al. Serum selenium concentration is associated with metabolic factors in the elderly: a cross-sectional study. Nutrition & Metabolism. 2010;7:38.

14. Lin CC, Huang JF, Tsai LY, Huang YL. Selenium, Iron, Copper, and Zinc Levels and Copper-to-Zinc Ratios in Serum of Patients at Different Stages of Viral Hepatic Diseases. Biological Trace Element Research. 2006;109: 15-23.

15. Rannem T, Ladefoge K, Hylander E, et al. Selenium Depletion in Patients on Home Parenteral Nutrition. Biological Trace Element Research. 1993;39:81-89.

16. Ravn-Haren G, Bügel S, Krath BN, et al. A short-term intervention trial with selenate, selenium-enriched yeast and selenium-enriched milk: effects on oxidative defense regulation. British Journal of Nutrition. 2008;99(1):883-892.

17. Huang JF, Hsu CP, Ouyang CH, et al. The impact of selenium supplementation on trauma patients—systematic review and meta-analysis. Nutrients. 2022;14(2).

18. Kong L, Wu Q, Liu B. The impact of selenium administration on severe sepsis or septic shock: a meta-analysis of randomized controlled trials. Afr Health Sci. 2021;21(1): 277-285.

19. Strachan S, Wyncoll D. Why might selenium supplementation be beneficial in sepsis? J Intensive Care Soc. 2009;10(1):38-43.

20. Dellinger RP, Levy M, Rhodes A, et al. Surviving sepsis campaign: International guidelines for management of severe sepsis and septic shock, 2012. Intensive Care Med. 2013;39(2).

21. Zimmermann T, Albrecht S, Kühne H, et. al., Selensubstitution bei Sepsispadenten. Medizinisehe Klinik. 1997;92(Suppl. III):3-4.

22. Angstwurm MW, Engelmann L, Zimmermann T, et al. Selenium in Intensive Care (SIC): Results of a prospective randomized, placebo-controlled, multiple-center study in patients with severe systemic inflammatory response syndrome, sepsis, and septic shock. Crit Care Med. 2007;35:118-126.

23. Manzanares W, Biestro A, Torre M, et al. High-dose selenium reduces ventilator-associated pneumonia and illness severity in critically ill patients with systemic inflammation. Intensive Care Med. 2011;37: 1120-1127.

24. Andrews PJ, Avenell A, Noble DW, et al. Randomised trial of glutamine, selenium, or both, to supplement parenteral nutrition for critically ill patients. BMJ. 2011;342:d1542.

25. González CM, Luna AH, Villalobos JA, et al. Efecto antiinflamatorio del selenio en pacientes sépticos. Rev Asoc Mex Med Crit y Ter Int. 2009;23(4):199-205.

26. Forceville X, Laviolle B, Annane D, et al. Effects of high doses of selenium, as sodium selenite, in septic shock: a placebo-controlled, randomized, double-blind, phase II study. Critical Care 2007;11(4):R73.

27. Bloos F, Trips E, Nierhaus A, et al. Effect of Sodium Selenite Administration and Procalcitonin-Guided Therapy on Mortality in Patients with Severe Sepsis or Septic Shock: A Randomized Clinical Trial. JAMA Intern Med. 2016;176(9):1266-76.

28. Huang TS, Shyu YC, Chen HY, et al. Effect of Parenteral Selenium Supplementation in Critically Ill Patients: A Systematic Review and Meta-Analysis. PLoS One. 2013;8(1):e54431.

29. Manzanares W, Lemieux M, Elke G, et al. High-dose intravenous selenium does not improve clinical outcomes in the critically ill: a systematic review and meta-analysis. Critical Care 2016;20:356.

30. Lee WJ, Chen YL, Chu YW, Chien DS. Comparison of glutathione peroxidase-3 protein expression and enzyme bioactivity in normal subjects and patients with sepsis. Clin Chim Acta 2019;489:177-182.

31. Xia Y, Hill KE, Byrne DW, et al. Effectiveness of selenium supplements in a low-selenium area of China. Am J Clin Nutr. 2005;81(4):829-34.

32. Manzanares W, Biestro A, Galusso F, et al. High-dose selenium for critically ill patients with systemic inflammation: Pharmacokinetics and pharmacodynamics of selenious acid: A pilot study. Nutrition. 2010;26:634-640.

33. Mertens K, Lowes DA, Webster NR, et al. Low zinc and selenium concentrations in sepsis are associated with oxidative damage and inflammation. Br J Anaesth. 2015;114(6):990-999.

34. Fiaccadori E, Sabatino A, Barazzoni R, et al. ESPEN guideline on clinical nutrition in hospitalized patients with acute or chronic kidney disease. Clin Nutr. 2021;40(4):1644-1668.

35. Gyawali B, Ramakrishna K, Dhamoon AS. Sepsis: The evolution in definition, pathophysiology, and management. SAGE Open Med. 2019;7:205031211983504.

36. Bloos F, Trips E, Nierhaus A, et al. Effect of Sodium Selenite Administration and Procalcitonin-Guided Therapy on Mortality in Patients With Severe Sepsis or Septic Shock: A Randomized Clinical Trial. JAMA Intern Med. 2016;176(9):1266-1276.

37. Chelkeba L, Ahmadi A, Abdollahi M, et al. The effect of high-dose parenteral sodium selenite in critically ill patients following sepsis: a clinical and mechanistic study. Indian J Crit Care Med. 2017;21:287-293.

38. Vijayan AL, Ravindran S, Saikant R, Lakshmi S, Kartik R, Manoj G. Procalcitonin: a promising diagnostic marker for sepsis and antibiotic therapy. J Intensive Care. 2017;5(1).