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- Open Access
Clinical and biological effects of high-dose sodium selenite, continuously administered in septic shock
- Published: 27 October 2011
Keywords
- Selenium
- Septic Shock
- Selenite
- Procalcitonin
- Sodium Selenite
Introduction
Sodium selenite (Na2SeO3) has been proposed as an early treatment of septic shock with discrepant results [1–3]. Beneficial action is mainly believed through improvement of major antioxidant selenoenzymes, but could on the contrary be related to a therapeutic oxidant action reducing activity of hyperactivated circulating phagocytic cells [4]. It has been suggested that the absence of beneficial effect of high-dose Na2SeO3 continuously administered [2] might be related to toxicity, especially on the lung, of too much selenium (Se) as mentioned in recent parenteral nutrition guidelines in intensive care [5]. On additional clinical and biological data, our purpose was to assess if there was argument for Na2SeO3 toxicity, especially on the lung, under continuous administration of high-dose Na2SeO3 in the SERENITE study.
Methods
In a randomized, double-blind multicenter study performed in 60 septic shock patients [2], the efficacy and tolerance of Na2SeO3 (4 mg Se on day 1 (D1), then 1 mg/day during 9 days or placebo) were evaluated on all components of the SOFA score measured daily, infection rate, and plasma Se, selenoprotein-P (Sel-P), glutathione peroxidase (GPx), lipid peroxidation, cytokines, and procalcitonin measured at D0, D4, D7, D10 and D14.
Results
PaO2/FiO2 according to group and time
Baseline (D0) | D2 | D3 | D4 | D7 | D10 | D14 | |
|---|---|---|---|---|---|---|---|
Na2SeO3 | 20 ± 15 | 23 ± 12 | 24 ± 10 | 25 ± 14 | 26 ± 11 | 30 ± 13 | 28 ± 15 |
Placebo | 22 ± 13 | 21 ± 11 | 25 ± 13 | 26 ± 11 | 28 ± 14 | 33 ± 17 | 36 ± 17 |
P value | 0.60 | 0.37 | 0.92 | 0.81 | 0.65 | 0.52 | 0.13 |
Plasma Se concentration according to groups and time. Data presented as mean ± SD (μmol/l). Reference value for plasma Se concentration: 1 ± 0.15 μmol/l. Treated group indicated in blue and nontreated in green.
Conclusion
Continuous administration of high doses of Na2SeO3 (4 mg Se D1) did not induce any deleterious effect in septic shock patients. We did not observe a beneficial effect, contrasting with a comparable study administering Na2SeO3 in bolus, potentially more toxic [1]. In agreement with results obtained on a peritonitis sheep model [6], our data support a therapeutic oxidant action of Na2SeO3, opening a new field in septic shock treatment based on oxidant selenocompounds.
Declarations
Acknowledgements
The authors thank all the investigators, biochemists, pharmacists and clinical research team involved in the SERENITE Study, the Minister of Health for financing, and Meaux Hospital as promotor. XF is the co-inventor with DV of patent FR 98 10889, PCT N°FR 99/02.66 (delivered: US 6,844,012 B1, Au 760 534; EP 1107767), and has ownership of the corresponding patent. XF is the main shareholder of a small start-up named SÉRÉNITÉ-Forceville devoted to early diagnosis and treatment of septic shock especially by selenocompounds.
Authors’ Affiliations
References
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Copyright
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
