High-dose selenium substitution in sepsis: a prospective randomized clinical trial
- 785 Downloads
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.
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.
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.
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.
KeywordsSelenium Systemic inflammatory response syndrome Sepsis Organ failure Glutathione peroxidase C-reactive protein Procalcitonin Prealbumin Antioxidants
Conflict of interest
The authors declare that they have no competing interests.
- 1.Engel C, Brunkhorst FM, Bone HG, Brunkhorst R, Gerlach H, Grond S, Gruendling M, Huhle G, Jaschinski U, John S, Mayer K, Oppert M, Olthoff D, Quintel M, Ragaller M, Rossaint R, Stuber F, Weiler N, Welte T, Bogatsch H, Hartog C, Loeffler M, Reinhart K (2007) Epidemiology of sepsis in Germany: results from a national prospective multicenter study. Intensive Care Med 33:606–618PubMedCrossRefGoogle Scholar
- 9.Kuklinski B, Zimmermann T, Schweder R (1995) Decreasing mortality in acute pancreatitis with sodium selenite. Clinical results of 4 years antioxidant therapy. Med Klin (Munich) 90(Suppl 1):36–41Google Scholar
- 12.Forceville X, Laviolle B, Annane D, Vitoux D, Bleichner G, Korach JM, Cantais E, Georges H, Soubirou JL, Combes A, Bellissant E (2007) Effects of high doses of selenium, as sodium selenite, in septic shock: a placebo-controlled, randomized, double-blind, phase II study. Crit Care 11:R73PubMedCrossRefGoogle Scholar
- 14.Angstwurm MW, Engelmann L, Zimmermann T, Lehmann C, Spes CH, Abel P, Strauss R, Meier-Hellmann A, Insel R, Radke J, Schuttler J, Gartner R (2007) Selenium in Intensive Care (SIC): results of a prospective randomized, placebo-controlled, multiple-center study in patients with severe systemic inflammatory response syndrome, sepsis, and septic shock. Crit Care Med 35:118–126PubMedCrossRefGoogle Scholar
- 17.Vincent JL, de Mendonca A, Cantraine F, Moreno R, Takala J, Suter PM, Sprung CL, Colardyn F, Blecher S (1998) Use of the SOFA score to assess the incidence of organ dysfunction/failure in intensive care units: results of a multicenter, prospective study. Working group on “sepsis-related problems” of the European Society of Intensive Care Medicine. Crit Care Med 26:1793–1800PubMedGoogle Scholar
- 25.Martindale RG, McClave SA, Vanek VW, McCarthy M, Roberts P, Taylor B, Ochoa JB, Napolitano L, Cresci G (2009) Guidelines for the provision and assessment of nutrition support therapy in the adult critically ill patient: Society of Critical Care Medicine and American Society for Parenteral and Enteral Nutrition: Executive Summary. Crit Care Med 37:1757–1761PubMedCrossRefGoogle Scholar
- 27.Berger MM, Baines M, Raffoul W, Benathan M, Chiolero RL, Reeves C, Revelly JP, Cayeux MC, Senechaud I, Shenkin A (2007) Trace element supplementation after major burns modulates antioxidant status and clinical course by way of increased tissue trace element concentrations. Am J Clin Nutr 85:1293–1300PubMedGoogle Scholar
- 29.Avenell A, Noble DW, Barr J, Engelhardt T (2004) Selenium supplementation for critically ill adults. Cochrane Database of Systematic Reviews, Issue 4. Art. No.: CD003703. doi: 10.1002/14651858.CD003703.pub2
- 40.Levy MM, Dellinger RP, Townsend SR, Linde-Zwirble WT, Marshall JC, Bion J, Schorr C, Artigas A, Ramsay G, Beale R, Parker MM, Gerlach H, Reinhart K, Silva E, Harvey M, Regan S, Angus DC (2010) The Surviving Sepsis Campaign: results of an international guideline-based performance improvement program targeting severe sepsis. Intensive Care Med 36:222–231PubMedCrossRefGoogle Scholar