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

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.