title: High-dose selenium for critically ill patients with systemic inflammation: pharmacokinetics and pharmacodynamics of selenious acid: a pilot study.
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 micromol over 2 h and thereafter 10.12 micromol/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 micromol over 2 h and thereafter 20.24 micromol 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.
  
  
  CONCLUSIONS
  A bolus loading dose of selenite providing 2000 microg of selenium (25.30 micromol) followed by a CIV of 1600 microg/d (20.24 micromol/d) for 10 d is most effective at returning serum selenium to physiologic levels and safely maximizing glutathione peroxidase activity.
authors.affiliation: Department of Critical Care Medicine, Hospital de Clínicas Dr. Manuel Quintela, School of Medicine (University Hospital), UDELAR, Montevideo, Uruguay. wmanzanares@adinet.com.uy
authors.forename: William
authors.initials: W
authors.lastname: Manzanares
authors.forename: Alberto
authors.initials: A
authors.lastname: Biestro
authors.forename: Federico
authors.initials: F
authors.lastname: Galusso
authors.forename: María H
authors.initials: MH
authors.lastname: Torre
authors.forename: Nelly
authors.initials: N
authors.lastname: Mañáy
authors.forename: Gianella
authors.initials: G
authors.lastname: Facchin
authors.forename: Gil
authors.initials: G
authors.lastname: Hardy
mesh_terms: D000328:Adult; D000368:Aged; D016638:Critical Illness; D004305:Dose-Response Relationship, Drug; D005260:Female; D005979:Glutathione Peroxidase / Q000097:blood*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011446:Prospective Studies; D012643:Selenium / Q000097:blood; D018038:Sodium Selenite / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D018746:Systemic Inflammatory Response Syndrome / Q000097:blood / Q000188:drug therapy*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D005979:Glutathione Peroxidase; D012643:Selenium; D018038:Sodium Selenite