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Annals of Intensive Care
Published in: Annals of Intensive Care 1/2015

Open Access 01-12-2015 | Research

The effect of parenteral selenium on outcomes of mechanically ventilated patients following sepsis: a prospective randomized clinical trial

Authors: Legese Chelkeba, Arezoo Ahmadi, Mohammad Abdollahi, Atabak Najafi, Mohammad Hosein Ghadimi, Reza Mosaed, Mojtaba Mojtahedzadeh

Published in: Annals of Intensive Care | Issue 1/2015

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Abstract

Background

Sepsis and septic shock is characterized by oxidative stress that mainly promotes systemic inflammation and organ failure due to excessive free radical production and depletion of antioxidant defenses. Therefore, we investigated the effect of selenium administration on antioxidant status, levels of cytokines and clinical outcomes.

Methodology

This study was a prospective randomized control trial (RCT) whereby patients received selenium as sodium selenite (2 mg IV bolus followed by 1.5 mg continuous infusion for 14 days) plus standard therapy. The control group received standard therapy without selenium. The primary endpoint was 28-day mortality. The changes in the mean levels of glutathione peroxidase (GPX) activity, IL-6, IL-8 and IL-10, the incidence of ventilator-associated pneumonia (VAP) and other secondary endpoints were also recorded. VAP was broken down into early VAP and late VAP to see the clinical significance of each. We also recorded any adverse outcomes from selenium infusion.

Results

Over 24-month period, 54 patients were recruited and randomized and an intention to treat (ITT) principle was applied (selenium, n = 29; control, n = 25) in the final analysis. There was no statistically significant difference between the two groups in 28-day mortality although it was lower in the selenium group compared with the control group: 9 (31 %) in the selenium versus 10 (40 %) in the control groups (p = 0.49). At day 0, GPX activity was 0.185 ± 0.3 versus 0.19 ± 0.3 U/mL (p = 0.9), day 3, GPX activity was 0.52 ± 0.5 versus 0.17 ± 0.2 U/mL (p = 0.02), at day 7 it was 0.55 ± 0.5 versus 0.24 ± 0.3 U/mL (p = 0.032), at day 10 it was 0.62 ± 0.7 versus 0.33 ± 0.4 U/mL (p = 0.048) and at day 14 it was 1.1 ± 1 versus 0.89 ± 1 U/mL (p = 0.70) for the selenium versus control groups, respectively. However, there were no significant differences between the mean plasma levels of all the three inflammatory cytokines at any point in time between the two groups. There was a significant reduction in occurrence of VAP in the selenium group compared with the control group (55.2 versus 84 %, p = 0.023), respectively.

Conclusion

High-dose selenium administration within the time frame of early goal-directed therapy was not resulted in reduction of 28-day mortality, but increased the activity of glutathione peroxidase with no effect on the levels of inflammatory cytokines at any point in time in mechanically ventilated septic patients. However, selenium supplementation in mechanically ventilated patients following sepsis was associated with reduced occurrence of VAP.
Trial registration: IRCT201212082887N4 at WHO Clinical Trial Registry, August 29, 2014
Literature
1.
Angus DC, Linde-Zwirble WT, Lidicker J, Clermont G, Carcillo J, Pinsky MR. Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of care. Crit Care Med. 2001;29(7):1303–10.CrossRefPubMed
2.
Annane D, Aegerter P, Jars-Guincestre MC, Guidet B. Current epidemiology of septic shock: the CUB-Rea Network. Am J Respir Crit Care Med. 2003;168(2):165–72.CrossRefPubMed
3.
Martin GS, Mannino DM, Eaton S, Moss M. The epidemiology of sepsis in the United States from 1979 through 2000. N Engl J Med. 2003;348(16):1546–54.CrossRefPubMed
4.
Sands KE, Bates DW, Lanken PN, Graman PS, Hibberd PL, Kahn KL, et al. Epidemiology of sepsis syndrome in 8 academic medical centers. JAMA. 1997;278(3):234–40.CrossRefPubMed
5.
Tanriover M, Guven G, Sen D, Unal S, Uzun O. Epidemiology and outcome of sepsis in a tertiary-care hospital in a developing country. Epidemiol Infect. 2006;134(02):315–22.PubMedCentralCrossRefPubMed
6.
Gogos CA, Drosou E, Bassaris HP, Skoutelis A. Pro-versus anti-inflammatory cytokine profile in patients with severe sepsis: a marker for prognosis and future therapeutic options. J Infect Dis. 2000;181(1):176–80.CrossRefPubMed
7.
Cavaillon J-M. Pathophysiological role of pro- and anti-inflammatory cytokines in sepsis. Sepsis. 1998;2(2):127–40.CrossRef
8.
9.
Oda S, Hirasawa H, Shiga H, Nakanishi K, Matsuda K-I, Nakamua M. Sequential measurement of IL-6 blood levels in patients with systemic inflammatory response syndrome (SIRS)/sepsis. Cytokine. 2005;29(4):169–75.CrossRefPubMed
10.
Manzanares WBA, Torre MH, Galusso F, Facchin G, Hardy G. High-dose selenium reduces ventilator-associated pneumonia and illness severity in critically ill patients with systemic inflammation. Intensive Care Med. 2011;37(7):1120–7.CrossRefPubMed
11.
Grossman RF, Fein A. Evidence-based assessment of diagnostic tests for ventilator-associated pneumonia: executive summary. Chest J. 2000;117(4_suppl_2):177S–81S.CrossRef
12.
Chastre J, Fagon J-Y. Ventilator-associated pneumonia. Am J Respir Crit Care Med. 2002;165(7):867–903.CrossRefPubMed
13.
Safdar N, Dezfulian C, Collard HR, Saint S. Clinical and economic consequences of ventilator-associated pneumonia: a systematic review. Crit Care Med. 2005;33(10):2184–93.CrossRefPubMed
14.
Amin A. Clinical and economic consequences of ventilator-associated pneumonia. Clin Infect Dis. 2009;49(1):36–43.CrossRef
15.
Bouadma L, Sonneville R, Garrouste-Orgeas M, Darmon M, Souweine B, Voiriot G, et al. Ventilator-associated events: prevalence, outcome, and relationship with ventilator-associated pneumonia. Crit Care Med. 2015;43(9):1798–806.CrossRefPubMed
16.
Driscoll DM, Copeland PR. Mechanism and regulation of selenoprotein synthesis. Annu Rev Nutr. 2003;23(1):17–40.CrossRefPubMed
17.
de Vega JMA, Díaz J, Serrano E, Carbonell LF. Oxidative stress in critically ill patients with systemic inflammatory response syndrome. Crit Care Med. 2002;30(8):1782–6.CrossRef
18.
Motoyama T, Okamoto K, Kukita I, Hamaguchi M, Kinoshita Y, Ogawa H. Possible role of increased oxidant stress in multiple organ failure after systemic inflammatory response syndrome. Crit Care Med. 2003;31(4):1048–52.CrossRefPubMed
19.
Vunta H, Belda BJ, Arner RJ, Channa Reddy C, Vanden Heuvel JP, Sandee pPrabhu K. Selenium attenuates pro-inflammatory gene expression in macrophages. Mol Nut Food Res. 2008;52(11):1316–23.CrossRef
20.
Vunta H, Davis F, Palempalli UD, Bhat D, Arner RJ, Thompson JT, et al. The anti-inflammatory effects of selenium are mediated through 15-deoxy-Δ12, 14-prostaglandin J2 in macrophages. J Biol Chem. 2007;282(25):17964–73.CrossRefPubMed
21.
Forceville X, Vitoux D, Gauzit R, Combes A, Lahilaire P, Chappuis P. Selenium, systemic immune response syndrome, sepsis, and outcome in critically ill patients. Crit Care Med. 1998;26(9):1536–44.CrossRefPubMed
22.
Valenta J, Brodska H, Drabek T, Hendl J, Kazda A. High-dose selenium substitution in sepsis: a prospective randomized clinical trial. Intensive Care Med. 2011;37(5):808–15.CrossRefPubMed
23.
24.
Kong Z, Wang F, Ji S, Deng X, Xia Z. Selenium supplementation for sepsis: a meta-analysis of randomized controlled trials. Am J Emerg Med. 2013;31(8):1170–5.CrossRefPubMed
25.
Miller N, Miller M, Hill LT. The impact of antioxidant supplementation on clinical outcomes in the critically ill: a meta-analysis. South Afr J Crit Care. 2013;29(1):18–26.CrossRef
26.
Visser J, Labadarios D, Blaauw R. Micronutrient supplementation for critically ill adults: a systematic review and meta-analysis. Nutrition. 2011;27(7):745–58.CrossRefPubMed
27.
Dellinger RP, Levy MM, Rhodes A, Annane D, Gerlach H, Opal SM, et al. Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock, 2012. Intensive Care Med. 2013;39(2):165–228.CrossRefPubMed
28.
Bone RC, Balk RA, Cerra FB, Dellinger RP, Fein AM, Knaus WA, et al. Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. The ACCP/SCCM Consensus Conference Committee. American College of Chest Physicians/Society of Critical Care Medicine. Chest J. 1992;101(6):1644–55.CrossRef
29.
Rello J, Lode H, Cornaglia G, Masterton R. A European care bundle for prevention of ventilator-associated pneumonia. Intensive Care Med. 2010;36(5):773–80.CrossRefPubMed
30.
Angstwurm MW, Engelmann L, Zimmermann T, Lehmann C, Spes CH, Abel P, et al. 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. 2007;35(1):118–26.CrossRefPubMed
31.
Mishra V, Baines M, Elizabeth Perry S, Jeremy McLaughlin P, Carson J, Wenstone R, et al. Effect of selenium supplementation on biochemical markers and outcome in critically ill patients. Clinical Nutrition. 2007;26(1):41–50.CrossRefPubMed
32.
Forceville X, Laviolle B, Annane D, Vitoux D, Bleichner G, Korach J-M, et al. Effects of high doses of selenium, as sodium selenite, in septic shock: a placebo-controlled, randomized, double-blind, phase II study. Crit Care. 2007;11(4):73.CrossRef
33.
Manzanares W, Biestro A, Torre MH, Galusso F, Facchin G, Hardy G. High-dose selenium reduces ventilator-associated pneumonia and illness severity in critically ill patients with systemic inflammation. Intensive Care Med. 2011;37(7):1120–7.CrossRefPubMed
34.
Mouncey PR, Osborn TM, Power GS, Harrison DA, Sadique MZ, Grieve RD, et al. Trial of early, goal-directed resuscitation for septic shock. N Engl J Med. 2015;372(14):1301–11.CrossRefPubMed
35.
Peake SL, Delaney A, Bailey M, Bellomo R, Cameron PA, Cooper DJ, et al. Goal-directed resuscitation for patients with early septic shock. N Engl J Med. 2014;371(16):1496.CrossRefPubMed
36.
Yealy DM, Kellum JA, Huang DT, Barnato AE, Weissfeld LA, Pike F, et al. A randomized trial of protocol-based care for early septic shock. N Engl J Med. 2014;370(18):1683–93.CrossRefPubMed
37.
Manzanares W, Dhaliwal R, Jiang X, Murch L, Heyland DK. Antioxidant micronutrients in the critically ill: a systematic review and meta-analysis. Crit Care. 2012;16(2):R66.PubMedCentralCrossRefPubMed
38.
Landucci F, Mancinelli P, De Gaudio AR, Virgili G. Selenium supplementation in critically ill patients: a systematic review and meta-analysis. J Crit Care. 2014;29(1):150–6.CrossRefPubMed
39.
Alhazzani W, Jacobi J, Sindi A, Hartog C, Reinhart K, Kokkoris S, et al. The effect of selenium therapy on mortality in patients with sepsis syndrome: a systematic review and meta-analysis of randomized controlled trials. Crit Care Med. 2013;41(6):1555–64.CrossRefPubMed
40.
Huang T-S, Shyu Y-C, Chen H-Y, Lin L-M, Lo C-Y, Yuan S-S, et al. Effect of parenteral selenium supplementation in critically ill patients: a systematic review and meta-analysis. PLoS One. 2013;8(1):e54431.PubMedCentralCrossRefPubMed
41.
Heyland DK, Dhaliwal R, Suchner U, Berger MM. Antioxidant nutrients: a systematic review of trace elements and vitamins in the critically ill patient. Intensive Care Med. 2005;31(3):327–37.CrossRefPubMed
42.
Huang Z, Rose AH, Hoffmann PR. The role of selenium in inflammation and immunity: from molecular mechanisms to therapeutic opportunities. Antioxid Redox Signal. 2012;16(7):705–43.PubMedCentralCrossRefPubMed
43.
Dinarello CA. Proinflammatory and anti-inflammatory cytokines as mediators in the pathogenesis of septic shock. Chest J. 1997;112(6):321–9.CrossRef
44.
Ulloa L, Tracey KJ. The ‘cytokine profile’: a code for sepsis. Trends Mol Med. 2005;11(2):56–63.CrossRefPubMed
45.
Pontes-Arruda A, Aragão AMA, Albuquerque JD. Effects of enteral feeding with eicosapentaenoic acid, γ-linolenic acid, and antioxidants in mechanically ventilated patients with severe sepsis and septic shock. Crit Care Med. 2006;34(9):2325–33.CrossRefPubMed
46.
Landesberg G, Levin PD, Gilon D, Goodman S, Georgieva M, Weissman C, et al. Myocardial dysfunction in severe sepsis and septic shock—no correlation with inflammatory cytokines in real-life clinical setting. Chest. 2015;148(1):93–102.CrossRefPubMed
47.
Berger MM, Baines M, Raffoul W, Benathan M, Chiolero RL, Reeves C, et al. Trace element supplementation after major burns modulates antioxidant status and clinical course by way of increased tissue trace element concentrations. Am J Clin Nutr. 2007;85(5):1293–300.PubMed
48.
Berger MM, Eggimann P, Heyland DK, Chioléro RL, Revelly J-P, Day A, et al. Reduction of nosocomial pneumonia after major burns by trace element supplementation: aggregation of two randomised trials. Crit Care. 2006;10(6):153.CrossRef
49.
Kollef MH, Silver P, Murphy DM, Trovillion E. The effect of late-onset: ventilator-associated pneumonia in determining patient mortality. Chest J. 1995;108(6):1655–62.CrossRef
50.
Valles J, Pobo A, Garcia-Esquirol O, Mariscal D, Real J, Fernandez R. Excess ICU mortality attributable to ventilator-associated pneumonia: the role of early versus late onset. Intensive Care Med. 2007;33(8):1363–8.CrossRefPubMed
51.
Bercault N, Boulain T. Mortality rate attributable to ventilator-associated nosocomial pneumonia in an adult intensive care unit: a prospective case-control study. Crit Care Med. 2001;29(12):2303–9.CrossRefPubMed
52.
Moine P, Timsit J-F, De Lassence A, Troché G, Fosse J-P, Alberti C, et al. Mortality associated with late-onset pneumonia in the intensive care unit: results of a multi-center cohort study. Intensive Care Med. 2002;28(2):154–63.CrossRefPubMed
53.
Rivers E, Nguyen B, Havstad S, Ressler J, Muzzin A, Knoblich B, et al. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med. 2001;345(19):1368–77.CrossRefPubMed
54.
Chelkeba L, Ahmadi A, Abdollahi M, Najafi A, Mojtahedzadeh M. Early goal-directed therapy reduces mortality in adult patients with severe sepsis and septic shock: systematic review and meta-analysis. Indian J Crit Care Med. 2015;19(7):401–11.PubMedCentralCrossRefPubMed
Metadata
Title
The effect of parenteral selenium on outcomes of mechanically ventilated patients following sepsis: a prospective randomized clinical trial
Authors
Legese Chelkeba
Arezoo Ahmadi
Mohammad Abdollahi
Atabak Najafi
Mohammad Hosein Ghadimi
Reza Mosaed
Mojtaba Mojtahedzadeh
Publication date
01-12-2015
Publisher
Springer Paris
Published in
Annals of Intensive Care / Issue 1/2015
Electronic ISSN: 2110-5820
DOI
https://doi.org/10.1186/s13613-015-0071-y

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