High-dose intravenous selenium does not improve clinical outcomes in the critically ill: a systematic review and meta-analysis.

BACKGROUND: Selenium (Se) is an essential trace element with antioxidant, anti-inflammatory, and immunomodulatory effects. So far, several randomized clinical trials (RCTs) have demonstrated that parenteral Se may improve clinical outcomes in intensive care unit (ICU) patients. Since publication of our previous systematic review and meta-analysis on antioxidants in the ICU, reports of several trials have been published, including the largest RCT on Se therapy. The purpose of the present systematic review was to update our previous data on intravenous (IV) Se in the critically ill. METHODS: We searched MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials. We included RCTs with parallel groups comparing parenteral Se as single or combined therapy with placebo. Potential trials were evaluated according to specific eligibility criteria, and two reviewers abstracted data from original trials in duplicate independently. Overall mortality was the primary outcome; secondary outcomes were infections, ICU length of stay (LOS), hospital LOS, ventilator days, and new renal dysfunction. RESULTS: A total of 21 RCTs met our inclusion criteria. When the data from these trials were aggregated, IV Se had no effect on mortality (risk ratio [RR] 0.98, 95 % CI 0.90-1.08, P = 0.72, heterogeneity I 2 = 0 %). In addition, when the results of ten trials in which researchers reported on infections were statistically aggregated, there was no significant treatment effect of parenteral Se (RR 0.95, 95 % CI 0.88-1.02, P = 0.15, I 2 = 0 %). There was no positive or negative effect of Se therapy on ICU and hospital LOS, renal function, or ventilator days. CONCLUSIONS: In critically ill patients, IV Se as monotherapy does not improve clinical outcomes.

Translation and adaptation of the NUTRIC Score to identify critically ill patients who benefit the most from nutrition therapy.

INTRODUCTION AND OBJECTIVES: Due to the scarcity of tools to assess the nutritional risk in critically ill patients, the NUTrition Risk in the Critically ill Score (NUTRIC Score) was developed and validated primarily in a limited population to quantify the risk of adverse events that may be modified by aggressive nutrition therapy. The objective of this study was to translate and adapt the NUTRIC Score into Portuguese language for further demonstrate its feasibility and clinical utility in Brazilian Intensive Care Units (ICUs). METHODS: This translation and adaptation process is part of a study for the validation of NUTRIC Score in Brazil. Translation was performed according to standardized steps: initial translation, synthesis of translations, back-translation, revision and application of the instrument by specialists and evaluation of cultural adaptation. We conducted a pilot study within 50 patients mechanically ventilated for more than 48 h in four ICUs in Southern Brazil to determine the prevalence of patients who were the most likely to benefit from aggressive nutrition therapy. RESULTS: The translation and adaptation process produced a valid version of NUTRIC Score in the Portuguese language. The translated version was easily introduced into four Brazilian ICUs and the prevalence of patients with high score and likely to benefit from aggressive nutritional intervention (mean age 61.4 ± 15.3 years) was 46% (23 individuals, 95%CI 0.33-0.60). CONCLUSIONS: The NUTRIC Score has been successfully translated into Portuguese and the prevalence of nutritionally-high risk patients may be around 50% in Brazilian ICUs.

Intravenous fish oil lipid emulsions in critically ill patients: an updated systematic review and meta-analysis.

INTRODUCTION: Intravenous fish oil (FO) lipid emulsions (LEs) are rich in ω-3 polyunsaturated fatty acids, which exhibit anti-inflammatory and immunomodulatory effects. We previously demonstrated that FO-containing LEs may be able to decrease mortality and ventilation days in patients who are critically ill. Since 2014, several additional randomized controlled trials (RCTs) of FO-containing LEs have been published. Therefore, the purpose of this systematic review was to update our previous systematic review with the aim of elucidating the efficacy of FO-containing LEs on clinical outcomes of patients who are critically ill. METHODS: We searched electronic databases from 1980 to 2014. We included four new RCTs conducted in critically ill adult patients in which researchers evaluated FO-containing LEs in parenterally or enterally fed patients. RESULTS: A total of 10 RCTs (n = 733) met inclusion criteria. The mean methodological score was 8 (range, 3 to 12). No effect on overall mortality was found. When we aggregated the results of five RCTs in which infections were reported, we found that FO-containing LEs significantly reduced infections (risk ratio (RR) = 0.64; 95% confidence interval (CI), 0.44 to 0.92; P = 0.02; heterogeneity I (2) = 0%). Subgroup analysis demonstrated that predominantly enteral nutrition-based trials showed a tendency toward a reduction in mortality (RR = 0.69; 95% CI, 0.40 to 1.18; P =0.18; heterogeneity I (2) =35%). High-quality trials showed a significant reduction in hospital length of stay (LOS) (weighted mean difference = -7.42; 95% CI, -11.89 to -2.94; P = 0.001), whereas low-quality trials had no effect (P = 0.45). The results of the test for subgroup differences in hospital LOS was significant (P = 0.001). CONCLUSION: FO-containing LEs may be associated with a reduction in infections and also could be associated with a reduction in duration of ventilation and hospital LOS. Further large-scale RCTs are warranted and should be aimed at consolidating potential positive treatment effects.

Pharmaconutrition with selenium in critically ill patients: what do we know?

Selenium is a component of selenoproteins with antioxidant, anti-inflammatory, and immunomodulatory properties. Systemic inflammatory response syndrome (SIRS), multiorgan dysfunction (MOD), and multiorgan failure (MOF) are associated with an early reduction in plasma selenium and glutathione peroxidase activity (GPx), and both parameters correlate inversely with the severity of illness and outcomes. Several randomized clinical trials (RCTs) evaluated selenium therapy as monotherapy or in antioxidant cocktails in intensive care unit (ICU) patient populations, and more recently several meta-analyses suggested benefits with selenium therapy in the most seriously ill patients. However, the largest RCT on pharmaconutrition with glutamine and antioxidants, the REducing Deaths due to Oxidative Stress (REDOXS) Study, was unable to find any improvement in clinical outcomes with antioxidants provided by the enteral and parenteral route and suggested harm in patients with renal dysfunction. Subsequently, the MetaPlus study demonstrated increased mortality in medical patients when provided extra glutamine and selenium enterally. The treatment effect of selenium may be dependent on the dose, the route of administration, and whether administered with other nutrients and the patient population studied. Currently, there are few small studies evaluating the pharmacokinetic profile of intravenous (IV) selenium in SIRS, and therefore more data are necessary, particularly in patients with MOD, including those with renal dysfunction. According to current knowledge, high-dose pentahydrate sodium selenite could be given as an IV bolus injection (1000-2000 µg), which causes transient pro-oxidant, cytotoxic, and anti-inflammatory effects, and then followed by a continuous infusion of 1000-1600 µg/d for up to 10-14 days. Nonetheless, the optimum dose and efficacy still remain controversial and need to be definitively established.

SodiUm SeleniTe Adminstration IN Cardiac Surgery (SUSTAIN CSX-trial): study design of an international multicenter randomized double-blinded controlled trial of high dose sodium-selenite administration in high-risk cardiac surgical patients.

BACKGROUND: Cardiac surgery has been shown to result in a significant decrease of the antioxidant selenium, which is associated with the development of multiorgan dysfunction and increased mortality. Thus, a large-scale study is needed to investigate the effect of perioperative selenium supplementation on the occurrence of postoperative organ dysfunction. METHODS/DESIGN: We plan a prospective, randomized double-blind, multicenter controlled trial, which will be conducted in North and South America and in Europe. In this trial we will include 1,400 high-risk patients, who are most likely to benefit from selenium supplementation. This includes patients scheduled for non-emergent combined and/or complex procedures, or with a predicted operative mortality of ≥ 5% according to the EuroSCORE II. Eligible patients will be randomly assigned to either the treatment group (bolus infusion of 2,000 µg sodium selenite immediately prior to surgery, followed by an additional dosage of 2,000 µg at ICU admission, and a further daily supplementation of 1,000 µg up to 10 days or ICU discharge) or to the control group (placebo administration at the same time points).The primary endpoint of this study is a composite of 'persistent organ dysfunction' (POD) and/or death within 30 days from surgery (POD + death). POD is defined as any need for life-sustaining therapies (mechanical ventilation, vasopressor therapy, mechanical circulatory support, continuous renal replacement therapy, or new intermittent hemodialysis) at any time within 30 days from surgery. DISCUSSION: The SUSTAIN-CSX™ study is a multicenter trial to investigate the effect of a perioperative high dosage sodium selenite supplementation in high-risk cardiac surgical patients. TRIAL REGISTRATION: This trial was registered at Clinicaltrials.gov (identifier: NCT02002247) on 28 November 2013.

Parenteral fish oil lipid emulsions in the critically ill: a systematic review and meta-analysis.

INTRODUCTION: ω-3 Polyunsaturated fatty acids contained in fish oils (FO) possess major anti-inflammatory, antioxidant, and immunologic properties that could be beneficial during critical illness. We hypothesized that parenteral FO-containing emulsions may improve clinical outcomes in the critically ill. METHODS: We searched computerized databases from 1980-2012. We included randomized controlled trials (RCTs) conducted in critically ill adult patients that evaluated FO-containing emulsions, either in the context of parenteral nutrition (PN) or enteral nutrition (EN). RESULTS: A total of 6 RCTs (n = 390 patients) were included; the mean methodological score of all trials was 10 (range, 6-13). When the results of these studies were aggregated, FO-containing emulsions were associated with a trend toward a reduction in mortality (risk ratio [RR], 0.71; 95% confidence interval [CI], 0.49-1.04; P = .08; heterogeneity I (2) = 0%) and a reduction in the duration of mechanical ventilation (weighted mean difference in days [WMD], -1.41; 95% CI, -3.43 to 0.61; P = .17). However, this strategy had no effect on infections (RR, 0.76; 95% CI, 0.42-1.36; P = .35) and intensive care unit length of stay (WMD, -0.46; 95% CI, -4.87 to 3.95; P = .84, heterogeneity I (2) = 75%). CONCLUSION: FO-containing lipid emulsions may be able to decrease mortality and ventilation days in the critically ill. However, because of the paucity of clinical data, there is inadequate evidence to recommend the routine use of parenteral FO. Large, rigorously designed RCTs are required to elucidate the efficacy of parenteral FO in the critically ill.

Antioxidant micronutrients in the critically ill: a systematic review and meta-analysis.

INTRODUCTION: Critical illness is characterized by oxidative stress, which is a major promoter of systemic inflammation and organ failure due to excessive free radical production, depletion of antioxidant defenses, or both. We hypothesized that exogenous supplementation of trace elements and vitamins could restore antioxidant status, improving clinical outcomes. METHODS: We searched computerized databases, reference lists of pertinent articles and personal files from 1980 to 2011. We included randomized controlled trials (RCTs) conducted in critically ill adult patients that evaluated relevant clinical outcomes with antioxidant micronutrients (vitamins and trace elements) supplementation versus placebo. RESULTS: A total of 21 RCTs met inclusion criteria. When the results of these studies were statistically aggregated (n = 20), combined antioxidants were associated with a significant reduction in mortality (risk ratio (RR) = 0.82, 95% confidence interval (CI) 0.72 to 0.93, P = 0.002); a significant reduction in duration of mechanical ventilation (weighed mean difference in days = -0.67, 95% CI -1.22 to -0.13, P = 0.02); a trend towards a reduction in infections (RR= 0.88, 95% CI 0.76 to 1.02, P = 0.08); and no overall effect on ICU or hospital length of stay (LOS). Furthermore, antioxidants were associated with a significant reduction in overall mortality among patients with higher risk of death (>10% mortality in control group) (RR 0.79, 95% CI 0.68 to 0.92, P = 0.003) whereas there was no significant effect observed for trials of patients with a lower mortality in the control group (RR = 1.14, 95% 0.72 to 1.82, P = 0.57). Trials using more than 500 µg per day of selenium showed a trend towards a lower mortality (RR = 0.80, 95% CI 0.63 to 1.02, P = 0.07) whereas trials using doses lower than 500 µg had no effect on mortality (RR 0.94, 95% CI 0.67 to 1.33, P = 0.75). CONCLUSIONS: Supplementation with high dose trace elements and vitamins may improve outcomes of critically ill patients, particularly those at high risk of death.