Skip to main content
Erschienen in: Intensive Care Medicine 7/2011

01.07.2011 | Original

High-dose selenium reduces ventilator-associated pneumonia and illness severity in critically ill patients with systemic inflammation

verfasst von: William Manzanares, Alberto Biestro, María H. Torre, Federico Galusso, Gianella Facchin, Gil Hardy

Erschienen in: Intensive Care Medicine | Ausgabe 7/2011

Einloggen, um Zugang zu erhalten

Abstract

Purpose

To confirm the pharmacodynamics and evaluate the efficacy of high-dose selenium (Se) administered by continuous infusion, following an initial loading bolus of selenite, on clinical outcome in critically ill patients with systemic inflammatory response syndrome (SIRS).

Methods

Prospective, placebo-controlled, randomized, single-blinded phase II study in a multidisciplinary university hospital intensive care unit (ICU). Two groups of patients with SIRS, age >18 years, and Acute Physiology and Chronic Health Evaluation (APACHE) II ≥15 (n = 35) were randomized to receive either placebo or intravenous selenite as a bolus-loading dose of 2,000 μg Se followed by continuous infusion of 1,600 μg Se per day for 10 days. Blood samples were analyzed before randomization (day 0) then at days 3, 7, and 10. Clinical outcome was assessed by Sequential Organ Failure Assessment (SOFA) score. Hospital-acquired pneumonia including ventilator-associated pneumonia (VAP), adverse events, and other safety parameters were monitored as secondary endpoints.

Results

SOFA score decreased significantly in the selenite group at day 10 (1.3 ± 1.2 versus 4.6 ± 2.0, p = 0.0001). Early VAP rate was lower in the selenite group (6.7% versus 37.5%, p = 0.04), and hospital-acquired pneumonia was lower after ICU discharge (p = 0.03). Glutathione peroxidase-3 (GPx-3) activity increased in both groups, reaching a maximum at day 7 (0.62 ± 0.24 versus 0.28 ± 0.14 U/mL, p = 0.001) in the selenite group. No adverse events attributable to selenite were observed.

Conclusions

Daily infusion of 1,600 μg Se (as selenite), following an initial bolus of 2,000 μg, is novel and without short-term adverse events. High-dose parenteral selenite significantly increases Se status, improves illness severity, and lowers incidence of hospital-acquired pneumonia including early VAP for SIRS patients in ICU.
Anhänge
Nur mit Berechtigung zugänglich
Literatur
1.
Zurück zum Zitat Meduri GU, Johanson WG (1992) International consensus conference: clinical investigation of VAP. Chest 102:551S–552SPubMedCrossRef Meduri GU, Johanson WG (1992) International consensus conference: clinical investigation of VAP. Chest 102:551S–552SPubMedCrossRef
2.
3.
Zurück zum Zitat Safdar N, Dezfulian C, Collard HR, Saint S (2005) Clinical and economic consequences of ventilator-associated pneumonia: a systematic review. Crit Care Med 33:2184–2193PubMedCrossRef Safdar N, Dezfulian C, Collard HR, Saint S (2005) Clinical and economic consequences of ventilator-associated pneumonia: a systematic review. Crit Care Med 33:2184–2193PubMedCrossRef
4.
Zurück zum Zitat Rello J, Ollendorf DA, Oster G, Vera-Llonch M, Bellm L, Redman R, Kollef MH, VAP Outcomes Scientific Advisory Group (2002) Epidemiology and outcomes of ventilator-associated pneumonia in a large US database. Chest 122:2115–2121PubMedCrossRef Rello J, Ollendorf DA, Oster G, Vera-Llonch M, Bellm L, Redman R, Kollef MH, VAP Outcomes Scientific Advisory Group (2002) Epidemiology and outcomes of ventilator-associated pneumonia in a large US database. Chest 122:2115–2121PubMedCrossRef
7.
Zurück zum Zitat Vincent JL, Forceville X (2008) Critically elucidating the role of selenium. Curr Opin Anaesthesiol 21:148–154PubMedCrossRef Vincent JL, Forceville X (2008) Critically elucidating the role of selenium. Curr Opin Anaesthesiol 21:148–154PubMedCrossRef
8.
Zurück zum Zitat Manzanares W, Biestro A, Galusso F, Torre MH, Mañay N, Pittini G, Facchín G, Hardy G (2009) Serum selenium and glutathione peroxidase-3 activity: biomarkers of systemic inflammation in the critically ill. Intensive Care Med 35:882–889PubMedCrossRef Manzanares W, Biestro A, Galusso F, Torre MH, Mañay N, Pittini G, Facchín G, Hardy G (2009) Serum selenium and glutathione peroxidase-3 activity: biomarkers of systemic inflammation in the critically ill. Intensive Care Med 35:882–889PubMedCrossRef
9.
Zurück zum Zitat Kim IY, Stadtman TC (1997) Inhibition of NF-kB DNA binding and NO induction in human T cells and lung adenocarcinoma cells by selenite treatment. Proc Natl Acad Sci USA 94:12904–12907PubMedCrossRef Kim IY, Stadtman TC (1997) Inhibition of NF-kB DNA binding and NO induction in human T cells and lung adenocarcinoma cells by selenite treatment. Proc Natl Acad Sci USA 94:12904–12907PubMedCrossRef
10.
Zurück zum Zitat Kretz-Remy C, Arrigo AP (2001) Selenium: a key element that controls NF-κB activation and IκBα half-life. BioFactors 14:117–125PubMedCrossRef Kretz-Remy C, Arrigo AP (2001) Selenium: a key element that controls NF-κB activation and IκBα half-life. BioFactors 14:117–125PubMedCrossRef
11.
Zurück zum Zitat Maehira F, Miyagi I, Eguchi Y (2003) Selenium regulates transcription factor NF-kB activation during the acute phase reaction. Clin Chem Acta 334:163–171CrossRef Maehira F, Miyagi I, Eguchi Y (2003) Selenium regulates transcription factor NF-kB activation during the acute phase reaction. Clin Chem Acta 334:163–171CrossRef
12.
Zurück zum Zitat Eaton S (2006) The biochemical basis of antioxidant therapy in critical illness. Proc Nutr Soc 65:242–249PubMedCrossRef Eaton S (2006) The biochemical basis of antioxidant therapy in critical illness. Proc Nutr Soc 65:242–249PubMedCrossRef
13.
14.
Zurück zum Zitat 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 26:1536–1544PubMedCrossRef 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 26:1536–1544PubMedCrossRef
15.
16.
Zurück zum Zitat Manzanares W, Biestro A, Galusso F, Torre MH, Mañay N, Facchín G, Hardy G (2010) High-dose selenium for critically ill patients with systemic inflammation: a pilot study. Nutrition 26:634–640 Manzanares W, Biestro A, Galusso F, Torre MH, Mañay N, Facchín G, Hardy G (2010) High-dose selenium for critically ill patients with systemic inflammation: a pilot study. Nutrition 26:634–640
17.
Zurück zum Zitat Members of the American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference (1992) Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. Crit Care Med 20:864–873 Members of the American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference (1992) Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. Crit Care Med 20:864–873
18.
Zurück zum Zitat Bernard GR, Artigas A, Brigham KL, Carlet J, Falke K, Hudson L, Lamy M, Legall JR, Morris A, Spragg R (1994) The American-European consensus conference on ARDS. Definition, mechanisms, relevant outcomes, and clinical trial coordination. Am J Respir Crit Care Med 149:818–824PubMed Bernard GR, Artigas A, Brigham KL, Carlet J, Falke K, Hudson L, Lamy M, Legall JR, Morris A, Spragg R (1994) The American-European consensus conference on ARDS. Definition, mechanisms, relevant outcomes, and clinical trial coordination. Am J Respir Crit Care Med 149:818–824PubMed
19.
Zurück zum Zitat Martindale RG, McClave SA, Vanek VW, McCarthy M, Roberts P, Taylor B, Ochoa JB, Napolitano L, Cresci G, American College of Critical Care Medicine, A.S.P.E.N. Board of Directors (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 of parenteral and enteral nutrition. Crit Care Med 37:1751–1761 Martindale RG, McClave SA, Vanek VW, McCarthy M, Roberts P, Taylor B, Ochoa JB, Napolitano L, Cresci G, American College of Critical Care Medicine, A.S.P.E.N. Board of Directors (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 of parenteral and enteral nutrition. Crit Care Med 37:1751–1761
20.
Zurück zum Zitat Manzanares W, Biestro A, Torre MH, Galusso F, Facchín G, Hardy G (2009) Clinical effects of high dose selenious acid in critically ill patients with systemic inflammation. J Parent Enteral Nutr 33:186 (Abstr. S36–34) Manzanares W, Biestro A, Torre MH, Galusso F, Facchín G, Hardy G (2009) Clinical effects of high dose selenious acid in critically ill patients with systemic inflammation. J Parent Enteral Nutr 33:186 (Abstr. S36–34)
21.
Zurück zum Zitat Rello J, Lode H, Cornaglia G, Masterton R, VAP Care Bundle Contributors (2010) A European care bundle for prevention of ventilator-associated pneumonia. Intensive Care Med 36:773–780PubMedCrossRef Rello J, Lode H, Cornaglia G, Masterton R, VAP Care Bundle Contributors (2010) A European care bundle for prevention of ventilator-associated pneumonia. Intensive Care Med 36:773–780PubMedCrossRef
22.
Zurück zum Zitat Weiss SJ (1989) Tissue destruction by neutrophils. N Engl J Med 329:365–376 Weiss SJ (1989) Tissue destruction by neutrophils. N Engl J Med 329:365–376
23.
Zurück zum Zitat Rao L, Puschner B, Prolia TA (2001) Gene expression profiling of low selenium status in the mouse intestine. J Nutr 131:3175–3181PubMed Rao L, Puschner B, Prolia TA (2001) Gene expression profiling of low selenium status in the mouse intestine. J Nutr 131:3175–3181PubMed
24.
Zurück zum Zitat Berger MM, Eggimann P, Heyland DK, Chioléro RL, Revelly JP, Day A, Raffou W, Shenkin A (2006) Reduction of nosocomial pneumonia after major burns by trace element supplementation: aggregation of two randomised trials. Critical Care 10:R153PubMedCrossRef Berger MM, Eggimann P, Heyland DK, Chioléro RL, Revelly JP, Day A, Raffou W, Shenkin A (2006) Reduction of nosocomial pneumonia after major burns by trace element supplementation: aggregation of two randomised trials. Critical Care 10:R153PubMedCrossRef
25.
Zurück zum Zitat Berger MM, Baines M, Raffoul W, Benathan M, Chiolero RL, Reeves C, Revelly JP, Cayeux MC, Sénéchaud 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 85:1293–1300PubMed Berger MM, Baines M, Raffoul W, Benathan M, Chiolero RL, Reeves C, Revelly JP, Cayeux MC, Sénéchaud 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 85:1293–1300PubMed
26.
Zurück zum Zitat Andrews PJD, Avenell A, Noble DW, Campbell MK, Croal BL, Simpson WG, Vale LD, Battison CG, Jenkinson DJ, Cook JA, and the SIGNET Trials Group (2011) Randomised trial of glutamine, selenium, or both, to supplement parenteral nutrition for critically ill patients. BMJ 342:d1542. doi:10.1136/bmj.d1542. Epub ahead of print Andrews PJD, Avenell A, Noble DW, Campbell MK, Croal BL, Simpson WG, Vale LD, Battison CG, Jenkinson DJ, Cook JA, and the SIGNET Trials Group (2011) Randomised trial of glutamine, selenium, or both, to supplement parenteral nutrition for critically ill patients. BMJ 342:d1542. doi:10.​1136/​bmj.​d1542. Epub ahead of print
27.
Zurück zum Zitat Angstwurm MWA, Engelmann L, Zimmermann T, Lehmann C, Abel P, Strauss R, Meier-Hellmann A, Insel R, Radke J, Schuttler J, Gartner R (2007) Selenium in Intensive Care (SIC) study. 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 35:118–126PubMedCrossRef Angstwurm MWA, Engelmann L, Zimmermann T, Lehmann C, Abel P, Strauss R, Meier-Hellmann A, Insel R, Radke J, Schuttler J, Gartner R (2007) Selenium in Intensive Care (SIC) study. 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 35:118–126PubMedCrossRef
28.
Zurück zum Zitat Heyland DK, Dhaliwal R, Suchner U, Berger MM (2005) Antioxidant nutrients: a systematic review of trace elements and vitamins in the critically ill patient. Intensive Care Med 31:327–337PubMedCrossRef Heyland DK, Dhaliwal R, Suchner U, Berger MM (2005) Antioxidant nutrients: a systematic review of trace elements and vitamins in the critically ill patient. Intensive Care Med 31:327–337PubMedCrossRef
29.
Zurück zum Zitat Canadian clinical practice guidelines for nutrition support in mechanically ventilated, critically ill adult patients. Supplemental antioxidants nutrients: parenteral selenium (2009) http://www.criticalcarenutrition.com. Last access: April 2010 Canadian clinical practice guidelines for nutrition support in mechanically ventilated, critically ill adult patients. Supplemental antioxidants nutrients: parenteral selenium (2009) http://​www.​criticalcarenutr​ition.​com. Last access: April 2010
30.
Zurück zum Zitat 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:R73PubMedCrossRef 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:R73PubMedCrossRef
31.
Zurück zum Zitat Wang Z, Forceville X, Van Antwerpen P, Piagnerelli M, Ahishakiye D, Macours P, De Backer D, Neve J, Vincent JL (2009) A large bolus, but not a continuous infusion, of sodium selenite improves outcome in peritonitis. Shock 32:140–146PubMedCrossRef Wang Z, Forceville X, Van Antwerpen P, Piagnerelli M, Ahishakiye D, Macours P, De Backer D, Neve J, Vincent JL (2009) A large bolus, but not a continuous infusion, of sodium selenite improves outcome in peritonitis. Shock 32:140–146PubMedCrossRef
32.
Zurück zum Zitat Schäper J, Samapaty R, Zakrzewicz A, Pries AR, Forceville X (2010) Effect of sodium selenite on LPS endothelial injury. Intensive Care Med 36(Suppl 2):S169 Schäper J, Samapaty R, Zakrzewicz A, Pries AR, Forceville X (2010) Effect of sodium selenite on LPS endothelial injury. Intensive Care Med 36(Suppl 2):S169
33.
Zurück zum Zitat Mishra V, Baines M, Perry SE, McLaughlin PJ, Carson J, Wenstone R, Shenkin A (2006) Effect of selenium supplementation on biochemical markers and outcome in critically ill patients. Clin Nutr 26:41–50PubMedCrossRef Mishra V, Baines M, Perry SE, McLaughlin PJ, Carson J, Wenstone R, Shenkin A (2006) Effect of selenium supplementation on biochemical markers and outcome in critically ill patients. Clin Nutr 26:41–50PubMedCrossRef
34.
Zurück zum Zitat Manzanares W, Hardy G (2009) Selenium supplementation in the critically ill. Posology and pharmacokinetics. Curr Opin Clin Nutr Metab Care 12:273–280PubMedCrossRef Manzanares W, Hardy G (2009) Selenium supplementation in the critically ill. Posology and pharmacokinetics. Curr Opin Clin Nutr Metab Care 12:273–280PubMedCrossRef
35.
Zurück zum Zitat Singer P, Berger MM, Van den Berghe G, Biolo G, Calder P, Forbes A, Griffiths R, Kreyman G, Leverve X, Pichard C (2009) ESPEN Guidelines on parenteral nutrition: intensive care. Clin Nutr 28:387–400PubMedCrossRef Singer P, Berger MM, Van den Berghe G, Biolo G, Calder P, Forbes A, Griffiths R, Kreyman G, Leverve X, Pichard C (2009) ESPEN Guidelines on parenteral nutrition: intensive care. Clin Nutr 28:387–400PubMedCrossRef
36.
Zurück zum Zitat Heyland DK (2007) Selenium supplementation in critically ill patients: can too much of a good thing be a bad thing? Crit Care 11:R153CrossRef Heyland DK (2007) Selenium supplementation in critically ill patients: can too much of a good thing be a bad thing? Crit Care 11:R153CrossRef
37.
Zurück zum Zitat Bopp BA, Sonders RC, Kesterson JW (1982) Metabolic fate of selected selenium compounds in laboratory animals and man. Drug Metab Rev 13:271–318PubMedCrossRef Bopp BA, Sonders RC, Kesterson JW (1982) Metabolic fate of selected selenium compounds in laboratory animals and man. Drug Metab Rev 13:271–318PubMedCrossRef
38.
Zurück zum Zitat Glover JR, Chu B (1970) Selenium and its industrial toxicity. Indust Med Surg 39:50–54 Glover JR, Chu B (1970) Selenium and its industrial toxicity. Indust Med Surg 39:50–54
39.
Zurück zum Zitat Andrews P (2010) Selenium and glutamine supplements: where are we heading? A critical care perspective. Curr Opin Clin Nutr Met Care 13:192–197CrossRef Andrews P (2010) Selenium and glutamine supplements: where are we heading? A critical care perspective. Curr Opin Clin Nutr Met Care 13:192–197CrossRef
40.
Zurück zum Zitat Valenta J, Brodska H, Drabek T, Hendl J, Kazda A (2011) High-dose selenium substitution in sepsis: a prospective randomized clinical trial. Intensive Care Med. doi 10.1007/s00134-011-2153-0. Epub ahead of print Valenta J, Brodska H, Drabek T, Hendl J, Kazda A (2011) High-dose selenium substitution in sepsis: a prospective randomized clinical trial. Intensive Care Med. doi 10.​1007/​s00134-011-2153-0. Epub ahead of print
Metadaten
Titel
High-dose selenium reduces ventilator-associated pneumonia and illness severity in critically ill patients with systemic inflammation
verfasst von
William Manzanares
Alberto Biestro
María H. Torre
Federico Galusso
Gianella Facchin
Gil Hardy
Publikationsdatum
01.07.2011
Verlag
Springer-Verlag
Erschienen in
Intensive Care Medicine / Ausgabe 7/2011
Print ISSN: 0342-4642
Elektronische ISSN: 1432-1238
DOI
https://doi.org/10.1007/s00134-011-2212-6

Weitere Artikel der Ausgabe 7/2011

Intensive Care Medicine 7/2011 Zur Ausgabe

Update AINS

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.