The effect of high-dose parenteral sodium selenite in critically ill patients following sepsis: A clinical and mechanistic study

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The incidence of sepsis was high and in the United States it is estimated to be 300/100,000 population per year. The spectrum of disease is a major cause of morbidity and mortality globally, with mortality in severe sepsis 5-fold higher than that for acute coronary syndrome or stroke. With advances in health-care services and technology, appropriate organ support, and treatment of the underlying inciting pathogens, the mortality rate is still 20%-50%. ring infection, pathogens or cellular components are recognized by receptors expressed on the surface of the innate immune cells known as pattern recognition receptors. The same receptors often recognize damage-associated molecular patterns (DAMPs) indicating that the similarities between pathogen-induced and inflammatory responses to cellular stress, injury, or necrosis. Trauma or injury generates danger-associated molecular patterns (i.e., high mobility group box-1 [HMGB-1], heat shock proteins, and S100 proteins) that augment toll-like receptors expressions such as pathogen-associated molecular patterns. HMGB-1, one of the most extensively studied DAMPs, is a protein involving in nuclear stabilization and gene transcription which, if released in large quantities into the extracellular environment, becomes a lethal mediator of systemic inflammation. significant amount of HMGB-1 levels have observed in majority of patients up to a week after the diagnosis of sepsis or septic shock and are correlated with the degree of organ dysfunction. troduction: Severe sepsis and septic shock is characterized by inflammation and oxidative stress. Selenium levels have been reported to be low due to loss or increased requirements during severe sepsis and septic shock. We investigated the effect of high-dose parenteral selenium administration in septic patients. Methods: A prospective, randomized control clinical trial was performed in septic patients. After randomization, patients in selenium group received high-dose parenteral sodium selenite (2 mg intravenous [IV] bolus followed by 1.5 mg IV continuous infusion daily for 14 days) plus standard therapy and the control group received standard therapy. The primary endpoint was mortality at 28 days. Changes in the mean levels of high mobility group box-1 (HMGB-1) protein and superoxide dismutase (SOD), duration of vasopressor therapy, incidence of acute renal failure, and 60 days' mortality were secondary endpoints. Results: Fifty-four patients were randomized into selenium group (n = 29) and control group (n = 25). There was no significant difference in 28-day mortality. No significant difference between the two groups with respect to the average levels of HMGB-1 protein and SOD at any point in time over the course of 14 days had observed. Conclusion: In early administration within the first 6 h of sepsis diagnosis, our study demonstrated that high-dose parenteral selenium administration had no significant effect either on 28-day mortality or the mean levels of HMGB-1 and SOD (Trial Registration: IRCT201212082887N4 at WHO Clinical Trial Registry, August 29, 2014).