A LARGE-BOLUS INJECTION, BUT NOT CONTINUOUS INFUSION OF SODIUM SELENITE IMPROVES OUTCOME IN PERITONITIS

Administration of sodium selenite in septic shock has been associated with apparently conflicting results that may be related to different dosing schedules. Bolus administration, leading to a transient pro-oxidative effect, could limit the inflammatory reaction and improve outcomes. We studied 21 anesthetized, mechanically ventilated, invasively monitored, and fluid-resuscitated sheep. Nine hours after inducing peritonitis by injection of autologous feces, the animals were randomized into three groups: (i) bolus injection (2 mg selenium as selenite, followed by 0.06 microg . kg-1 . h-1, n = 7); (ii) continuous infusion (4 microg . kg-1 . h-1 selenium, n = 7), or (iii) control (n = 7). No vasopressors or antibiotics were administered. All animals were monitored until spontaneous death. Peak plasma selenium values reached 4 to 14 micromol . L-1. Compared with the other groups, sheep given a bolus of sodium selenite had delayed hypotension with better maintained cardiac index, delayed hyperlactatemia, fewer sepsis-induced microvascular alterations, and a prolonged survival time (21.9 [bolus group] vs. 18.4 [continuous group] and 18.3 h [control group], P < 0.05). Hence, in this model of septic shock, the administration of a large bolus of sodium selenite (rather than a continuous administration) resulted in beneficial effects, probably by a transient oxidative effect.