Clinical PotpourriSelenium supplementation in critically ill patients: A systematic review and meta-analysis
Introduction
It is known that critical illness is typically characterized by oxidative stress, an alteration of the normal intracellular balance between the constant formation of oxidants, including reactive oxygen species (ROS) and reactive nitrogen species, and biological system's ability to detoxify the reactive intermediates or to repair the resulting damage [1], [2]. The increase of free radicals production, the inadequate response of the defense systems involved in the detoxification of the cell by ROS, or both of these conditions, can damage biologically relevant molecules, such as DNA, RNA, proteins, and unsaturated fatty acids of the cell membranes, which may ultimately lead to cell death [3], [4]. In critically ill patients, oxidative stress plays an important role in pathophysiological events leading to mitochondrial dysfunction and to systemic inflammatory response syndrome (SIRS), which may be complicated and result in acute respiratory distress syndrome and multiple organ dysfunction syndrome [5]. The antioxidant endogenous defense systems are extremely effective at counteracting ROS and the other reactive species. These antioxidants systems include both enzymatic proteins (such as superoxide dismutase, glutathione peroxidase, and catalase) and secondary antioxidants (or non-enzymatic) [6], [7].
Selenium is a trace mineral and it is essential to the function of glutathione peroxidase, since it is a structural component of the active site of this selenoenzyme [6]. Evidence suggests that in critically ill patients plasma selenium is significantly below the normal range; furthermore, it has been demonstrated that depletion of this micronutrient is associated with a worse clinical outcome: low selenium levels were associated with a greater number of infectious complications and a higher incidence of mortality [8].
Since it seems evident the theoretical rationale of the use of antioxidants, such as selenium, in the critically ill patient, in the last decades, several clinical trials attempted to demonstrate if selenium supplementation can determine some effective clinical benefit. Recently, Manzanares et al has published a comprehensive meta-analysis of the use of antioxidants in critically ill patients [9]. Selenium is universally recognized as one of the most promising antioxidants [10].
The aim of this study is to systematically review the efficacy of intravenous selenium supplementation as monotherapy in critically ill patients. Furthermore, we wished to assess the robustness of the conclusions by predicting the potential impact of a new study on the statistical significance and heterogeneity of our meta-analysis, which explores the need and potential impact of further research in this field.
Section snippets
Objectives
The primary aim of this review was to investigate the effect of intravenous selenium supplementation on 28-day mortality in critically ill patients.
The secondary objective was to evaluate the effects of selenium supplementation on other outcomes, such as mortality at 6 months, length of intensive care unit stay, number of nosocomial respiratory infections, incidence of renal failure and/or need for a renal replacement therapy (RRT).
Types of studies
We included all randomized (RCTs) and quasi-randomized
Description of studies
Our search results are detailed in Fig. 1.
Nineteen randomized controlled trials investigating intravenous selenium supplementation in critically ill patients were assessed for eligibility. Of these, we included 9 trials in our meta-analysis [12], [14], [15], [16], [17], [18], [19], [20], [21] and we described them herein (Table E1, available online).
We excluded the remaining 10 RCTs. The reasons for exclusion were a different kind of intervention, with administration of a cocktail containing
Discussion
Critically ill patients experience a severe state of oxidative stress, resulting in the dysfunction of the systems responsible for energy production in cells [1], [7]. This imbalance can cause damage to biologically relevant molecules and lead to mitochondrial dysfunction and SIRS with worsening of patient-related outcomes [4], [5].
In this context, supplemental selenium (in combination with standard therapy) could represent an important therapeutic option. Therefore, we performed a
Acknowledgments
We would like to thank Tessa Piazzini MLS, for her assistance and electronic searches advice during the identification of trials for this work.
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2021, Journal of NutritionDaily parenteral selenium therapy in critically ill patients: An updated systematic review and meta-analysis of randomized controlled trials
2021, Clinical Nutrition ESPENCitation Excerpt :It may be because of various doses and types of Se, route of administration (enteral or parenteral), and duration of therapy. On the other hand, there is no systematic review and meta-analysis to compare the effects of Se in doses lower or higher than 1000 μg per day and the duration lower or higher than 10 days, as mentioned at the ASPEN guidelines [7,8]. In addition, the previous meta-analysis resulted that Se supplementation has no effect on renal failure [9].
Effect of high-dose sodium selenite in cardiac surgery patients: A randomized controlled bi-center trial
2018, Clinical NutritionCitation Excerpt :Improved survival due to selenium supplementation (without or in combination with other antioxidants) was also demonstrated in critically ill patients by hitherto five meta-analyses [see 20, 21]. However, other studies on selenium supplementation in these patients did not find such beneficial effects [19–25]. In contrast to sepsis, elective cardiac surgery can be considered as quite ideal model to investigate the effect of selenium supplementation on inflammatory responses in man insofar the study population typically consists of a large number of suitable patients often suffering from a single (i.e. cardiac) disease without preexisting inflammation that underwent a defined hit (i.e. cardiac surgery) being followed by inflammatory responses over a relative short period of time.