Meta Analysis The effect of selenium therapy on mortality in patients with sepsis syndrome: a systematic review and meta-analysis of randomized controlled trials.
This review may be edited
Summary
Posted By:	Gordon S. Doig
E-Mail:	Gordon.Doig@EvidenceBased.net
Posted Date:	22 Oct 2013
Title:	The effect of selenium therapy on mortality in patients with sepsis syndrome: a systematic review and meta-analysis of randomized controlled trials.
Authors:	Alhazzani W, Jacobi J, Sindi A, Hartog C, Reinhart K, Kokkoris S, Gerlach H, Andrews P, Drabek T, Manzanares W, Cook DJ, Jaeschke RZ.
Reference:	Crit Care Med. 2013 Jun;41(6):1555-64. doi: 10.1097/CCM.0b013e31828a24c6.
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Abstract:	BACKGROUND: Patients with sepsis syndrome commonly have low serum selenium levels. Several randomized controlled trials have examined the efficacy of selenium supplementation on mortality in patients with sepsis. OBJECTIVE: To determine the efficacy and safety of high-dose selenium supplementation compared to placebo for the reduction of mortality in patients with sepsis. SOURCES OF DATA: We searched Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, SciFinder, and Clinicaltrials.gov. SELECTION CRITERIA: Randomized controlled parallel group trials comparing selenium supplementation in doses greater than daily requirement to placebo on the outcome of mortality in patients with sepsis syndrome. DATA COLLECTION AND ANALYSIS: Two reviewers independently applied eligibility criteria, assessed quality, and extracted data. The primary outcome was mortality; secondary outcomes were ICU length of stay, nosocomial pneumonia, and adverse events. Trial authors were contacted for additional or clarifying information. RESULTS: Nine trials enrolling a total of 792 patients were included. Selenium supplementation in comparison to placebo was associated with lower mortality (odds ratio, 0.73; 95% CI, 0.54, 0.98; p = 0.03; I = 0%). Among patients receiving and not receiving selenium, there was no difference in ICU length of stay (mean difference, 2.03; 95% CI, -0.51, 4.56; p = 0.12; I = 0%) or nosocomial pneumonia (odds ratio, 0.83; 95% CI, 0.28, 2.49; p = 0.74; I = 56%). Significant heterogeneity among trials in adverse event reporting precluded pooling of results. CONCLUSIONS: In patients with sepsis, selenium supplementation at doses higher than daily requirement may reduce mortality. We observed no impact of selenium on ICU length of stay or risk of nosocomial pneumonia.
Are the Results Valid?
1. Did the overview address a focused clinical question?
	Yes, the authors stipulate the intervention of interest, the patient population and outcome of interest.
2. Were the criteria used to select articles for inclusion appropriate?
	Yes, page 1556 stipulates the study eligibility criteria, however, the authors are not specific with regards to the inclusion or exclusion of pseudo-randomised trials. A specific statement of eligibility should be included.
3. Is it unlikely that important, relevant studies were missed?
	It is unlikely data was missed. The authors made an outstanding job of contacting experts and managed to obtain subgroup data on septic patients from two larger clinical trials. The authors also included foreign language publications.
4. Was the validity of the included studies appraised?
	Yes. Figure 2 provides a summary of the Risk of Bias (Validity) of the included trials. It does not appear pseudo-randomised trials were included. In addition to this summary figure, exact methods of maintenance of allocation concealment should be reported along with exact numbers of loss to follow-up.
5. Were assessments of studies reproducible?
	The authors report that two reviewers extracted data independently. All other steps were also undertaken independently by two reviewers.
6. Were the results similar from study to study?
	Heterogeneity was assessed using the I2 measure and the chi-square test. There was no heterogeneity in the primary outcomes.
What are the Results?
1. What are the overall results of the overview?
	Overall, selenium supplementation in comparison to placebo was associated with lower mortality (odds ratio, 0.73; 95% CI, 0.54, 0.98; p = 0.03; I2 = 0%). The NNT to prevent one death was 13 for an assumed controlled risk of 40%. This treatment effect was present in trials using > 500 mcg selenium per day (odds ratio, 0.67; 95% CI, 0.46 to 0.96; p = 0.03; I2 = 0%)
2. How precise were the results?
	See above for 95% confidence intervals.
Will the Results Help Me In Caring For My Patients?
1. Can the results be applied to my patient care
	Yes, IV selenium is readily available and relatively cheap. Please read individual trials to determine loading dose and dosing interval. This meta-analysis considered only IV selenium. Dosing for and effects of oral Se are not covered by these trials.
2. Were all clinically important outcomes considered?
	Yes. Lenght of stay, and pneumonia were reported. Costs were discussed briefly. Adverse events were also considered.
3. Are the benefits worth the harms and costs?
	Sepsis carries a high risk of mortality. The benefits of Se supplementation appear to outweigh the harms. A German clinical trial addressing this question has recently closed out with over 1,100 patients enrolled (ClinicalTrials.gov, NCT00832039). Analysis and results may take six months (from 22 Oct 2013) to be released and appear in print.
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