Clinical and biological effects of high-dose sodium selenite, continuously administered in septic shock

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

No deleterious effect of Na₂SeO₃ especially on the lung was observed for any clinical or biological variables. PaO₂/FiO₂ was strictly identical between groups (Table 1). As compared with placebo, mean time occurrences of infections were delayed in the treated group (18 ± 24 days vs. 34 ± 28 days, respectively; P < 0.0001). Plasma Se, Sel-P and GPx concentrations were increased at D4 in the treated group, achieving the high reference value for the plasma Se concentration (Figure 1).

Table 1.

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

Data presented as mean ± SD (KPa).

Figure 1.

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.

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.