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

Chelkeba L, Ahmadi A, Abdollahi M, Najafi A, Ghadimi MH, Mosaed R, Mojtahedzadeh M - Ann Intensive Care (2015)

Bottom Line: 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).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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Clinical Pharmacy, Faculty of Pharmacy, Tehran University of Medical Sciences, International campus (TUMS-IC), Tehran, Iran. legese.chelkeba@gmail.com.

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.

No MeSH data available.


Related in: MedlinePlus

The profile of study design and patient selection processes
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Fig1: The profile of study design and patient selection processes

Mentions: We assessed 364 patients for eligibility, of which 310 patients were excluded for the following reasons: 257 patients were excluded for not fulfilling the inclusion criteria, 2 patients decline not to participate and 51 patients for different reasons as described in detail in Fig. 1. Finally, 54 patients fulfilling the inclusion criteria recruited over a 2-year period (Selenium = 29, control = 25) were included in our final analysis according to the ITT principle although selenium was discounted in 3 patients due to rise in serum creatinine by the order of the senior clinician after 2 days of infusion. All patients followed either till they died or for 90 days, whichever happened first.Fig. 1


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

Chelkeba L, Ahmadi A, Abdollahi M, Najafi A, Ghadimi MH, Mosaed R, Mojtahedzadeh M - Ann Intensive Care (2015)

The profile of study design and patient selection processes
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4591221&req=5

Fig1: The profile of study design and patient selection processes
Mentions: We assessed 364 patients for eligibility, of which 310 patients were excluded for the following reasons: 257 patients were excluded for not fulfilling the inclusion criteria, 2 patients decline not to participate and 51 patients for different reasons as described in detail in Fig. 1. Finally, 54 patients fulfilling the inclusion criteria recruited over a 2-year period (Selenium = 29, control = 25) were included in our final analysis according to the ITT principle although selenium was discounted in 3 patients due to rise in serum creatinine by the order of the senior clinician after 2 days of infusion. All patients followed either till they died or for 90 days, whichever happened first.Fig. 1

Bottom Line: 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).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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Clinical Pharmacy, Faculty of Pharmacy, Tehran University of Medical Sciences, International campus (TUMS-IC), Tehran, Iran. legese.chelkeba@gmail.com.

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.

No MeSH data available.


Related in: MedlinePlus