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.
Conclusion
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.
Similar content being viewed by others
References
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 33:606–618
Hawker FH, Stewart PM, Snitch PJ (1990) Effects of acute illness on selenium homeostasis. Crit Care Med 18:442–446
Forceville X, Vitoux D, Gauzit R, Combes A, Lahilaire P, Chappuis P (1998) Selenium, systemic immune response syndrome, sepsis, and outcome in critically ill patients. Crit Care Med 26:1536–1544
Manzanares W, Biestro A, Galusso F, Torre MH, Manay N, Pittini G, Facchin G, Hardy G (2009) Serum selenium and glutathione peroxidase-3 activity: biomarkers of systemic inflammation in the critically ill? Intensive Care Med 35:882–889
Sakr Y, Reinhart K, Bloos F, Marx G, Russwurm S, Bauer M, Brunkhorst F (2007) Time course and relationship between plasma selenium concentrations, systemic inflammatory response, sepsis, and multiorgan failure. Br J Anaesth 98:775–784
Kazda A, Brodska H, Vinglerova H, Blaha J, Valenta J, Stritesky M, Zima T, Urban M (2004) Selenium and zinc plasmatic levels in intensive care patients. Crit Care 8(Suppl 1):P265
Vincent JL, Forceville X (2008) Critically elucidating the role of selenium. Curr Opin Anaesthesiol 21:148–154
Manzanares W, Hardy G (2009) Selenium supplementation in the critically ill: posology and pharmacokinetics. Curr Opin Clin Nutr Metab Care 12:273–280
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):36–41
Angstwurm MW, Schottdorf J, Schopohl J, Gaertner R (1999) Selenium replacement in patients with severe systemic inflammatory response syndrome improves clinical outcome. Crit Care Med 27:1807–1813
Mishra V, Baines M, Perry SE, McLaughlin PJ, Carson J, Wenstone R, Shenkin A (2007) Effect of selenium supplementation on biochemical markers and outcome in critically ill patients. Clin Nutr 26:41–50
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:R73
Berger MM, Soguel L, Shenkin A, Revelly JP, Pinget C, Baines M, Chiolero RL (2008) Influence of early antioxidant supplements on clinical evolution and organ function in critically ill cardiac surgery, major trauma, and subarachnoid hemorrhage patients. Crit Care 12:R101
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 35:118–126
Stawicki SP, Lyons M, Aloupis M, Sarani B (2007) Current evidence from phase III clinical trials of selenium supplementation in critically Ill patients: why should we bother? Mini Rev Med Chem 7:693–699
Heyland DK (2007) Selenium supplementation in critically ill patients: can too much of a good thing be a bad thing? Crit Care 11:153
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 26:1793–1800
Burk RF, Hill KE (2005) Selenoprotein P: an extracellular protein with unique physical characteristics and a role in selenium homeostasis. Annu Rev Nutr 25:215–235
Harrison I, Littlejohn D, Fell GS (1996) Distribution of selenium in human blood plasma and serum. Analyst 121:189–194
Fleck A, Raines G, Hawker F, Trotter J, Wallace PI, Ledingham IM, Calman KC (1985) Increased vascular permeability: a major cause of hypoalbuminemia in disease and injury. Lancet 1:781–784
Finley JW, Duffield A, Ha P, Vanderpool RA, Thomson CD (1999) Selenium supplementation affects the retention of stable isotopes of selenium in human subjects consuming diets low in selenium. Br J Nutr 82:357–360
Ashton K, Hooper L, Harvey LJ, Hurst R, Casgrain A, Fairweather-Tait SJ (2009) Methods of assessment of selenium status in humans: a systematic review. Am J Clin Nutr 89:2025S–2039S
Forceville X, Van Antwerpen P (2008) Selenocompounds and selenium. A biochemical approach to sepsis. In: Vincent JL (ed) Yearbook of intensive care and emergency medicine. Springer, Heidelberg, pp 454–469
Cohen HJ, Chovaniec ME, Mistretta D, Baker SS (1985) Selenium repletion and glutathione peroxidase—differential effects on plasma and red blood cell enzyme activity. Am J Clin Nutr 41:735–747
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 37:1757–1761
Singer P, Berger MM, Van den Berghe G, Biolo G, Calder P, Forbes A, Griffiths R, Kreyman G, Leverve X, Pichard C, Espen (2009) ESPEN guidelines on parenteral nutrition: intensive care. Clin Nutr 28:387–400
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 85:1293–1300
Berger MM, Cavadini C, Chiolero R, Guinchard S, Krupp S, Dirren H (1994) Influence of large intakes of trace elements on recovery after major burns. Nutrition 10:327–334; discussion 352
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
Zimmermann T, Albrecht S, Kuhne H, Vogelsang U, Grutzmann R, Kopprasch S (1997) Selenium administration in patients with sepsis syndrome. A prospective randomized study. Med Klin Munich 92(Suppl 3):3–4
Lindner D, Lindner J, Baumann G, Dawczynski H, Bauch K (2004) Investigation of antioxidant therapy with sodium selenite in acute pancreatitis. A prospective randomized blind trial. Med Klin Munich 99:708–712
Forceville X (2007) Effects of high doses of selenium, as sodium selenite, in septic shock patients a placebo-controlled, randomized, double-blind, multi-center phase II study—selenium and sepsis. J Trace Elem Med Biol 21(Suppl 1):62–65
Wang Z, Forceville X, Van Antwerpen P, Piagnerelli M, Ahishakiye D, Macours P, De Backer D, Neve J, Vincent JL (2009) A large-bolus injection, but not continuous infusion of sodium selenite improves outcome in peritonitis. Shock 32:140–146
Forceville X, Mostert V, Pierantoni A, Vitoux D, Le Toumelin P, Plouvier E, Dehoux M, Thuillier F, Combes A (2009) Selenoprotein P, rather than glutathione peroxidase, as a potential marker of septic shock and related syndromes. Eur Surg Res 43:338–347
Dunham CM, Fealk MH, Sever WE 3rd (2003) Following severe injury, hypocholesterolemia improves with convalescence but persists with organ failure or onset of infection. Crit Care 7:R145–R153
Devakonda A, George L, Raoof S, Esan A, Saleh A, Bernstein LH (2008) Transthyretin as a marker to predict outcome in critically ill patients. Clin Biochem 41:1126–1130
Rinaldi S, Landucci F, De Gaudio AR (2009) Antioxidant therapy in critically septic patients. Curr Drug Targets 10:872–880
Gartner R, Albrich W, Angstwurm MW (2001) The effect of a selenium supplementation on the outcome of patients with severe systemic inflammation, burn and trauma. Biofactors 14:199–204
Friedman G, Silva E, Vincent JL (1998) Has the mortality of septic shock changed with time. Crit Care Med 26:2078–2086
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 36:222–231
Conflict of interest
The authors declare that they have no competing interests.
Author information
Authors and Affiliations
Corresponding author
Electronic supplementary material
Below is the link to the electronic supplementary material.
Rights and permissions
About this article
Cite this article
Valenta, J., Brodska, H., Drabek, T. et al. High-dose selenium substitution in sepsis: a prospective randomized clinical trial. Intensive Care Med 37, 808–815 (2011). https://doi.org/10.1007/s00134-011-2153-0
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00134-011-2153-0