BACKGROUND

Hyperinflammation, cellular immune dysfunction, oxidative stress, and mitochondrial dysfunction are all characteristics of critical illness. Oxidative stress refers to an imbalance between free radicals (highly reactive oxygen molecules) and the body's ability to counteract their harmful effects through neutralization by antioxidants. Selenium is an antioxidant and a trace element that plays a pivotal role in this process.1 Evidence suggests that excessive oxidative stress plays a key role in the development of complications in critical illness, including systemic inflammatory response, which leads to acute respiratory distress disorder and multiple organ failure.2 Studies have reported that selenium supplementation in patients with critical illness resulted in fewer infections, less organ dysfunction, and reduced mortality compared with placebo.3-5

OBJECTIVE/S

The primary objective of this review was to examine the effects of nutrition supplemented with selenium compounds on mortality in critically ill patients. The secondary objective was to examine the relationship between these supplements and number of infections, duration of mechanical ventilation, length of intensive care stay, and length of hospital stay.

INTERVENTION/METHODS

The review included randomized controlled trials. The interventions considered were nutritional interventions by the enteral or parenteral route, or both, supplemented with additional selenium compared with nutritional care with by the same route without additional selenium. All types of selenium compounds were considered, including ebselen. Participants included adult patients with critical injuries, for example, burns, head injury, brain hemorrhage, and cerebrovascular accident, as well as those undergoing elective major surgery.

The primary outcomes considered were

* Overall mortality and

* Mortality by duration.

The secondary outcomes included

* Number of infectious complications;

* Adverse events;

* Length of stay in an intensive care unit;

* Number of days on a ventilator;

* Length of hospital stay;

* Quality of life after discharge; and

* Economic outcomes.

RESULTS

This review was originally conducted in 2004 and updated in 2007 and 2015.6 There were 6 new studies included in this review, making a total of 16 studies that involved a total of 2084 participants.

Thirteen trials (n = 1391 participants) of intravenous sodium selenite showed a significant reduction in overall mortality, based on very low quality of evidence. Nine trials (n = 1180) of intravenous sodium selenite were analyzed for 28-day mortality and no significant difference was found, based on very-low-quality evidence. Similar results were found for mortality at 90 days in 3 studies of intravenous sodium selenite (n = 614) and 2 trials (n = 588) of ebselen.

No significant advantage was found in intensive care patients treated with selenium supplementation for the outcome mortality in the 9 trials (n = 1168) included in the review. No significant difference for participants developing infection was identified for the use of intravenous sodium selenite or ebselen, based on very-low-quality evidence. Similarly, no effects were noted for adverse events. No clear evidence was found in favor of selenium supplementation for outcomes such as number of days on a ventilator, length of intensive care stay, or length of hospital stay, based on very-low-quality evidence.

The authors cautioned that most studies contained a low quality of trial methodology, including sample size, design, and outcomes. In addition, all included studies were at high risk of bias, and for these reasons, the results of this review should be viewed with caution.

CONCLUSIONS

Although a significant finding on longest follow-up mortality was identified, the low quality of evidence and high risk of bias in these studies mean that these results must be viewed with caution and do not support the routine use of selenium or ebselen supplementation in critically ill patients. Therefore, the use of selenium supplementation in these patients remains disputed. However, the authors note that they did not find any evidence to suggest that these interventions were harmful.

Implications for Practice

Critically ill patients including those with burns and head injuries are at high risk of oxidative stress, which, if left untreated, can lead to acute respiratory distress and multiple organ failure. Therefore, treatment with antioxidants that mitigates the harmful effects of free radicals in this process is desired; however, the evidence does not support routine treatment using the antioxidant selenium to supplement nutrition in these patients.

References