High-dose selenium for critically ill patients with systemic inflammation: Pharmacokinetics and pharmacodynamics of selenious acid: A pilot study
Received 15 February 2009; accepted 26 June 2009. published online 18 January 2010. Corrected Proof
Abstract
Objective
Systemic inflammatory response syndrome is characterized by increased urinary excretion of selenium and low serum concentration. Repletion by parenteral selenite is the most efficacious form of supplementation. However, the optimum safe dose and mode of administration remain controversial. We aimed to determine pharmacokinetic and pharmacodynamic profiles of selenite and estimate a safe dose to optimize selenium status.
Methods
A prospective, randomized, pilot study in 20 patients with systemic inflammatory response syndrome compared a high-dose (HD) group that received a loading dose of selenium as selenite 15.18 μmol over 2 h and thereafter 10.12 μmol/d as a continuous intravenous infusion (CIV) for 10 d with a very–high-dose (VHD) group that received a loading dose of 25.30 μmol over 2 h and thereafter 20.24 μmol as a CIV for 10 d. Clinical outcome was evaluated by length of stay in the intensive care unit, incidence of ventilator-associated pneumonia, and Sequential Organ Failure Assessment score.
Results
Patients in group HD (n = 10, age 54 ± 23 y) had an Acute Physiology and Chronic Health Evaluation II score of 23 ± 5 and a Sequential Organ Function Assessment score of 10 ± 2. Those in group VHD (n = 10, age 41 ± 19 y) had scores of 21 ± 7 and 8 ± 3, respectively. Pharmacokinetic concentration/time curves for serum selenium overlapped but were independent of dose, whereas the pharmacodynamics were different, showing maximum glutathione peroxidase activity only with VHD. Glutathione peroxidase decreased after day 7 independently of the selenium dose. Clinical outcomes were similar in both groups.
Conclusion
A bolus loading dose of selenite providing 2000 μg of selenium (25.30 μmol) followed by a CIV of 1600 μg/d (20.24 μmol/d) for 10 d is most effective at returning serum selenium to physiologic levels and safely maximizing glutathione peroxidase activity.
This work was supported in part by grants from the Comisión Sectorial para la Investigación Científica (CSIC), UdeLaR, and the Fondo Clemente Estable 2004/10.072, DyCIT, Ministerio de Educación y Cultura, Uruguay.
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