title: High-dose selenium substitution in sepsis: a prospective randomized clinical trial.
abstract: OBJECTIVE
  Systemic inflammatory response syndrome (SIRS) and sepsis remain the leading cause of death in the critically ill. A reduction in the antioxidant capacity, including selenoenzymes that are dependent on selenium (Se), could be a contributing factor. Se supplementation in septic patients have yielded conflicting results. We hypothesized that a high-dose Se supplementation would (1) improve markers of inflammation, nutrition and antioxidant defence, and (2) decrease mortality.
  
  
  METHODS
  This prospective, randomized, open-label, single-centre clinical trial included 150 patients with SIRS/sepsis and a SOFA score of >5. Patients in the Se+ group (n = 75) received Se for 14 days (1,000 μg on day 1,500 μg/day on days 2-14). Patients in both the control (Se-) group (n = 75) and the Se+ group received a standard Se dose (<75 μg/day). Plasma Se, whole-blood glutathione peroxidase (GPx) activity, C-reactive protein (CRP), procalcitonin (PCT), albumin, prealbumin and cholesterol levels, along with APACHE II and SOFA scores, were determined at baseline and on days 1-7 and day 14. Mortality was assessed at day 28.
  
  
  RESULTS
  Plasma Se and GPx activity were increased in the Se+ group from day 1 onwards. Negative correlations were demonstrated between plasma Se, CRP (P = 0.035), PCT (P = 0.022) and SOFA (P = 0.001) at admission but not on days 7 or 14. Prealbumin and cholesterol increased in the Se+ group versus the respective baselines. Mortality was similar between groups, with no gender differences.
  
  
  CONCLUSIONS
  High-dose Se substitution in patients with SIRS/sepsis increased plasma Se and GPx levels, but did not reduce mortality. Markers of inflammation were reduced similarly in both groups.
authors.affiliation: Department of Anaesthesiology, Resuscitation and Intensive Care, Charles University in Prague, Prague 2, Czech Republic. jiri.valenta@vfn.cz
authors.forename: Jiri
authors.initials: J
authors.lastname: Valenta
authors.forename: Helena
authors.initials: H
authors.lastname: Brodska
authors.forename: Tomas
authors.initials: T
authors.lastname: Drabek
authors.forename: Jan
authors.initials: J
authors.lastname: Hendl
authors.forename: Antonin
authors.initials: A
authors.lastname: Kazda
mesh_terms: D000328:Adult; D000368:Aged; D000975:Antioxidants / Q000032:analysis; D002097:C-Reactive Protein / Q000032:analysis; D002116:Calcitonin / Q000097:blood; D015740:Calcitonin Gene-Related Peptide; D016638:Critical Illness; D005260:Female; D005979:Glutathione Peroxidase / Q000097:blood; D006801:Humans; D008297:Male; D008875:Middle Aged; D009102:Multiple Organ Failure; D011228:Prealbumin / Q000032:analysis; D011446:Prospective Studies; D011498:Protein Precursors / Q000097:blood; D012643:Selenium / Q000008:administration & dosage* / Q000378:metabolism*; D018805:Sepsis / Q000097:blood / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology
chemical_list: D000975:Antioxidants; C000606589:CALCA protein, human; D011228:Prealbumin; D011498:Protein Precursors; D002116:Calcitonin; D002097:C-Reactive Protein; D005979:Glutathione Peroxidase; D012643:Selenium; D015740:Calcitonin Gene-Related Peptide