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Meta-Analysis
. 2015 Jul 27;2015(7):CD003703.
doi: 10.1002/14651858.CD003703.pub3.

Selenium supplementation for critically ill adults

Mikkel Allingstrup  1 , Arash Afshari
Affiliations
Meta-Analysis

Selenium supplementation for critically ill adults

Mikkel Allingstrup et al. Cochrane Database Syst Rev. .

Abstract

Background: Selenium is a trace mineral essential to health and has an important role in immunity, defence against tissue damage and thyroid function. Improving selenium status could help protect against overwhelming tissue damage and infection in critically ill adults. This Cochrane review was originally published in 2004 updated in 2007 and again 2015.

Objectives: The primary objective was to examine the effect of nutrition supplemented with selenium or ebselen on mortality in critically ill patients.The secondary objective was to examine the relationship between selenium or ebselen supplementation and number of infections, duration of mechanical ventilation, length of intensive care unit stay and length of hospital stay.

Search methods: In this update, we searched the current issue of the Cochrane Central Register of Controlled Trials, the Cochrane Library (2014, Issue 5); MEDLINE (Ovid SP, to May 20, 2014), EMBASE (Ovid SP, to May 20, 2014), CAB, BIOSIS and CINAHL. We handsearched the reference lists of the newest reviews and cross-checked with our search in MEDLINE. We contacted the main authors of included studies to request any missed, unreported or ongoing studies. The latest search was performed up to 21 May 2014. The search is now from inception until 21 May 2014.

Selection criteria: We included randomized controlled trials (RCTs) irrespective of publication status, date of publication, blinding status, outcomes published or language. We contacted the trial investigators and authors in order to retrieve relevant and missing data.

Data collection and analysis: Two review authors independently extracted data and we resolved any disagreements by discussion. Our primary outcome measure was all-cause mortality. We performed several subgroup and sensitivity analyses to assess the effects of selenium in critically ill patients. We presented pooled estimates of the effects of intervention as risk ratios (RRs) with 95% confidence intervals (CIs). We assessed the risk of bias through assessment of trial methodological components and the risk of random error through trial sequential analysis.

Main results: We included six new RCTs in this review update. In total we included 16 RCTs (2084 participants) in this review. Most trials were at high risk of bias. The availability of outcome data was limited and trials involving selenium supplementation were, with the exception of one trial, small regarding sample size. Thus the results must be interpreted with caution.Thirteen trials of intravenous sodium selenite showed a statistically significant reduction in overall mortality (RR 0.82, 95% CI 0.72 to 0.93, 1391 participants, very low quality of evidence). However, the overall point estimate on mortality is primarily influenced by trials of high risk of bias. Meta-analysis of three trials of ebselen had a RR of 0.83 (95% CI 0.52 to 1.34, 693 participants, very low quality of evidence).Nine trials of intravenous sodium selenite were analysed for 28 days mortality with no statistically significant difference (RR 0.84, 95% CI 0.69 to 1.02, 1180 participants, very low quality of evidence) while three trials were analysed for 90 days mortality with similar findings (RR 0.96, 95% Cl 0.78 to 1.18, 614 participants, very low quality of evidence).Two trials of ebselen were analysed for 90 days mortality and were not found to yield any benefit (RR 0.72, 95% Cl 0.42 to 1.22, 588 participants, very low quality of evidence).For mortality among intensive care patients selenium supplementation failed to indicate any statistically significant advantage (RR 0.88, 95% CI 0.77 to 1.01, nine trials, 1168 participants, very low quality of evidence).Six trials of intravenous sodium selenite found no statistically significant difference for participants developing infection (RR 0.96, 95% CI 0.75 to 1.23, 934 patients, very low quality of evidence). Similarly, three trials of ebselen provided data for participants developing infections (pyrexia, respiratory infections or meningitis) with no obvious benefit (RR 0.60, 95% CI 0.36 to 1.02, 685 participants, very low quality of evidence).Our analyses showed no effect of selenium or ebselen on adverse events (Selenium: RR 1.03, 95% Cl 0.85 to 1.24; six trials, 925 participants ; Ebselen: RR 1.16, 95% CI 0.40 to 3.36; two trials, 588 participants, very low quality of evidence).No clear evidence emerged in favour of selenium supplementation for outcomes such as number of days on a ventilator (mean difference (MD) -0.86, 95% CI -4.39 to 2.67, four trials, 191 participants, very low quality of evidence), length of intensive care unit stay (MD 0.54, 95% CI -2.27 to 3.34, seven trials, 934 participants, very low quality of evidence) or length of hospital stay (MD -3.33, 95% Cl -5.22 to -1.44, five trials, 693 participants, very low quality of evidence).The quality of trial methodology was low. Due to high risk of bias in the included trials, results must be interpreted with caution.

Authors' conclusions: Despite publication of a number of trials, the current evidence to recommend supplementation of critically ill patients with selenium or ebselen remains disputed. Trials are required which overcome the methodological inadequacies of the reviewed studies, particularly in relation to sample size, design and outcomes.

PubMed Disclaimer

Conflict of interest statement

Mikkel Allingstrup declares no conflicts of interest.

Arash Afshari declares no conflicts of interest.

Figures

1
1
Study flow diagram for the updated review. (In the original article, Avenell 2004, 10 studies were included and 11 studies were excluded with reasons. Three were awaiting classification, of which one has now been excluded (Kiessling 2006). Two studies are still ongoing).
2
2
'Risk of bias' graph: review authors' judgements about each 'Risk of bias' item presented as percentages across all included studies.
3
3
'Risk of bias' summary: review authors' judgements about each 'Risk of bias' item for each included study.
4
4
Funnel plot of comparison: 1.2 Overall mortality (regardless of the follow‐up period).
5
5
Trial sequential analysis (TSA) of all trials examining the effect of Selenium supplementation on mortality among critically ill. Using a control event proportion of 32% found in the included trials, with a type 1 error of 5% and a 18% relative risk reduction (80% power), the trial sequential monitoring boundary for benefit is not crossed by the z‐curve. However, these lines are very close to crossing each other which may indicate a probability of lack of random error for the conclusion of an effect of 18% relative risk reduction even though the required information size (N = 2605) has not yet been reached. However, caution must be exerted when interpreting the results of this TSA since all included studies are at high risk of bias and the intervention effect is likely to have been overestimated in the traditional meta‐analysis.
1.1
1.1. Analysis
Comparison 1 Selenium versus no selenium, Outcome 1 Overall mortality (regardless of the period of follow‐up).
2.1
2.1. Analysis
Comparison 2 Selenium versus no selenium, Outcome 1 Mortality by duration (Selenium).
2.2
2.2. Analysis
Comparison 2 Selenium versus no selenium, Outcome 2 Mortality by duration (Ebselen).
2.3
2.3. Analysis
Comparison 2 Selenium versus no selenium, Outcome 3 Mortality: ICU and pancreatitis (Selenium).
3.1
3.1. Analysis
Comparison 3 Selenium versus no selenium, Outcome 1 Number of infected participants.
4.1
4.1. Analysis
Comparison 4 Selenium versus no selenium, Outcome 1 Number of participants with adverse event.
4.2
4.2. Analysis
Comparison 4 Selenium versus no selenium, Outcome 2 Length of stay in ICU (Selenium).
4.3
4.3. Analysis
Comparison 4 Selenium versus no selenium, Outcome 3 Number of days on a ventilator (Selenium).
4.4
4.4. Analysis
Comparison 4 Selenium versus no selenium, Outcome 4 Length of hospital stay (Selenium).
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Geoghegan 2009 {published data only}
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