High-dose selenium reduces ventilator-associated pneumonia and illness severity in critically ill patients with systemic inflammation

Abstract

Purpose: To confirm the pharmacodynamics and evaluate the efficacy of high-dose selenium (Se) administered by continuous infusion, following an initial loading bolus of selenite, on clinical outcome in critically ill patients with systemic inflammatory response syndrome (SIRS).

Methods: Prospective, placebo-controlled, randomized, single-blinded phase II study in a multidisciplinary university hospital intensive care unit (ICU). Two groups of patients with SIRS, age >18 years, and Acute Physiology and Chronic Health Evaluation (APACHE) II ≥15 (n = 35) were randomized to receive either placebo or intravenous selenite as a bolus-loading dose of 2,000 μg Se followed by continuous infusion of 1,600 μg Se per day for 10 days. Blood samples were analyzed before randomization (day 0) then at days 3, 7, and 10. Clinical outcome was assessed by Sequential Organ Failure Assessment (SOFA) score. Hospital-acquired pneumonia including ventilator-associated pneumonia (VAP), adverse events, and other safety parameters were monitored as secondary endpoints.

Results: SOFA score decreased significantly in the selenite group at day 10 (1.3 ± 1.2 versus 4.6 ± 2.0, p = 0.0001). Early VAP rate was lower in the selenite group (6.7% versus 37.5%, p = 0.04), and hospital-acquired pneumonia was lower after ICU discharge (p = 0.03). Glutathione peroxidase-3 (GPx-3) activity increased in both groups, reaching a maximum at day 7 (0.62 ± 0.24 versus 0.28 ± 0.14 U/mL, p = 0.001) in the selenite group. No adverse events attributable to selenite were observed.

Conclusions: Daily infusion of 1,600 μg Se (as selenite), following an initial bolus of 2,000 μg, is novel and without short-term adverse events. High-dose parenteral selenite significantly increases Se status, improves illness severity, and lowers incidence of hospital-acquired pneumonia including early VAP for SIRS patients in ICU.