Thiamine pharmaconutrition in sepsis: Monotherapy, combined therapy, or neither? Current evidence on safety and efficacy.

Sepsis is a life-threatening condition characterized by multiorgan dysfunction due to an exaggerated host response to infection associated with a homeostatic failure. In sepsis, different interventions, aimed at improving clinical outcomes, have been tested over the past decades. Among these most recent strategies, intravenous high-dose micronutrients (vitamins and/or trace elements) have been investigated. According to current knowledge, sepsis is characterized by low thiamine levels, which are associated with illness severity, hyperlactatemia, and poor clinical outcomes. However, caution is needed about the clinical interpretation of thiamine blood concentration in critically ill patients, and the inflammatory status, based on C-reactive protein levels, should always be measured. In sepsis, parenteral thiamine has been administered as monotherapy or in combination with vitamin C and corticosteroids. Nevertheless, most of those trials failed to report clinical benefits with high-dose thiamine. The purpose of this review is to summarize the biological properties of thiamine and to examine current knowledge regarding the safety and efficacy of high-dose thiamine as pharmaconutrition strategy when administering singly or in combination with other micronutrients in critically ill adult patients with sepsis or septic shock. Our examination of the most up-to-date evidence concludes that Recommended Daily Allowance supplementation is relatively safe for thiamine-deficient patients. However, current evidence does not support pharmaconutrition with high-dose thiamine as a single therapy or as combination therapy aimed at improving clinical outcomes in critically ill septic patients. The best nutrient combination still needs to be determined, based on the antioxidant micronutrient network and the multiple interactions among different vitamins and trace elements. In addition, a better understanding of the pharmacokinetic and pharmacodynamic profiles of intravenous thiamine is needed. Future well-designed and powered clinical trials are urgently warranted before any specific recommendations can be made regarding supplementation in the critical care setting.

Clinical Nutrition and Human Rights. An International Position Paper.

The International Working Group for Patients' Right to Nutritional Care presents its position paper regarding nutritional care as a human right intrinsically linked to the right to food and the right to health. All people should have access to food and evidence-based medical nutrition therapy including artificial nutrition and hydration. In this regard, the hospitalized malnourished ill should mandatorily have access to screening, diagnosis, nutritional assessment, with optimal and timely nutritional therapy in order to overcome malnutrition associated morbidity and mortality, while reducing the rates of disease-related malnutrition. This right does not imply there is an obligation to feed all patients at any stage of life and at any cost. On the contrary, this right implies, from an ethical point of view, that the best decision for the patient must be taken and this may include, under certain circumstances, the decision not to feed. Application of the human rights-based approach to the field of clinical nutrition will contribute to the construction of a moral, political, and legal focus to the concept of nutritional care. Moreover, it will be the cornerstone to the rationale of political and legal instruments in the field of clinical nutrition.

Clinical nutrition and human rights. An international position paper.

The International Working Group for Patients' Right to Nutritional Care presents its position paper regarding nutritional care as a human right intrinsically linked to the right to food and the right to health. All people should have access to food and evidence-based medical nutrition therapy including artificial nutrition and hydration. In this regard, the hospitalized malnourished ill should mandatorily have access to screening, diagnosis, nutritional assessment, with optimal and timely nutritional therapy in order to overcome malnutrition associated morbidity and mortality, while reducing the rates of disease-related malnutrition. This right does not imply there is an obligation to feed all patients at any stage of life and at any cost. On the contrary, this right implies, from an ethical point of view, that the best decision for the patient must be taken and this may include, under certain circumstances, the decision not to feed. Application of the human rights-based approach to the field of clinical nutrition will contribute to the construction of a moral, political and legal focus to the concept of nutritional care. Moreover, it will be the cornerstone to the rationale of political and legal instruments in the field of clinical nutrition.

Pharmaconutrition revisited for critically ill patients with coronavirus disease 2019 (COVID-19): Does selenium have a place?

Coronavirus disease 2019 (COVID-19) is a global pandemic causing one of the biggest challenges for critical care medicine. Mortality from COVID-19 is much greater in elderly men, many of whom succumb to acute respiratory distress syndrome (ARDS) triggered by the viral infection. Because there is no specific antiviral treatment against COVID-19, new strategies are urgently needed. Selenium is an essential trace element with antioxidant and immunomodulatory effects. Poor nutritional status increases the pathogenicity of viruses and low selenium in particular can be a determinant of viral virulence. In the past decade, selenium pharmaconutrition studies have demonstrated some reduction in overall mortality, including how reduced incidence of ventilator-associated pneumonia and infectious complications such as ARDS in the critically ill. Consequently, we postulate that intravenous selenium therapy, could be part of the therapeutic fight against COVID-19 in intensive care unit patients with ARDS and that outcomes could be affected by age, sex, and body weight. Our working hypothesis addresses the question: Could high-dose selenite pharmaconutrition, as an early pharmacologic intervention, be effective at reducing the incidence and the progression from type 1 respiratory failure (non-ARDS) to severe ARDS, multiorgan failure, and new infectious complications in patients with COVID-19 patients?

Omega-3 polyunsaturated fatty acids in critically ill patients with acute respiratory distress syndrome: A systematic review and meta-analysis.

OBJECTIVE: Acute respiratory distress syndrome (ARDS) is characterized by an acute inflammatory response in the lung parenchyma leading to severe hypoxemia. Because of its anti-inflammatory and immunomodulatory properties, omega-3 polyunsaturated fatty acids (ω-3 PUFA) have been administered to ARDS patients, mostly by the enteral route, as immune-enhancing diets with eicosapentaenoic acid, γ-linolenic acid, and antioxidants. However, clinical benefits of ω-3 PUFAs in ARDS patients remain unclear because clinical trials have found conflicting results. Considering the most recent randomized controlled trials (RCTs) and recent change in administration strategies, the aim of this updated systematic review and meta-analysis was to evaluate clinical benefits of ω-3 PUFA administration on gas exchange and clinical outcomes in ARDS patients. METHODS: We searched for RCTs conducted in intensive care unit (ICU) patients with ARDS comparing the administration of ω-3 PUFAs to placebo. The outcomes assessed were PaO2-to-FiO2 ratio evaluated early (3-4 d) and later (7-8 d), mortality, ICU and hospital length of stay (LOS), length of mechanical ventilation (MV), and infectious complications. Two independent reviewers assessed eligibility, risk of bias, and abstracted data. Data were pooled using a random effect model to estimate the relative risk or weighted mean difference (WMD). RESULTS: Twelve RCTs (n = 1280 patients) met our inclusion criteria. Omega-3 PUFAs administration was associated with a significant improvement in early PaO2-to-FiO2 ratio (WMD = 49.33; 95% confidence interval [CI] 20.88-77.78; P = 0.0007; I2 = 69%), which persisted at days 7 to 8 (WMD = 27.87; 95% CI 0.75-54.99; P = 0.04; I2 = 57%). There was a trend in those receiving ω-3 PUFA toward reduced ICU LOS (P = 0.08) and duration of MV (P = 0.06), whereas mortality, hospital LOS, and infectious complications remained unchanged. Continuous enteral infusion was associated with reduced mortality (P = 0.02), whereas analysis restricted to enteral administration either with or without bolus found improved early PaO2 and FiO2 (P = 0.001) and MV duration (P = 0.03). Trials at higher risk of bias had a significant reduction in mortality (P = 0.04), and improvement in late PaO2-to-FiO2 ratio (P = 0.003). CONCLUSIONS: In critically ill patients with ARDS, ω-3 PUFAs in enteral immunomodulatory diets may be associated with an improvement in early and late PaO2-to-FiO2 ratio, and statistical trends exist for an improved ICU LOS and MV duration. Considering these results, administering ω-3 PUFAs appears a reasonable strategy in ARDS.

Omega-3 polyunsaturated fatty acids in cardiac surgery patients: An updated systematic review and meta-analysis.

BACKGROUND: Omega-3 polyunsaturated fatty acids (ω-3 PUFA) supplementation is an attractive therapeutic option for patients undergoing open-heart surgery due to their anti-inflammatory and anti-arrhythmic properties. Several randomized controlled trials (RCT) have found contradictory results for perioperative ω-3 PUFA administration. Therefore, we conducted an updated systematic review and meta-analysis evaluating the effects of perioperative ω-3 PUFA on some clinically important outcomes for cardiac surgery. METHODS: A systematic literature search was conducted to find RCT evaluating clinical outcomes after ω-3 PUFA therapy in adult patients undergoing cardiac surgery. Intensive care unit (ICU) length of stay (LOS) was the primary outcome; secondary outcomes were hospital LOS, postoperative atrial fibrillation (POAF), mortality and duration of mechanical ventilation (MV). Predefined subgroup analysis and sensibility analysis were performed. RESULTS: A total of 19 RCT including 4335 patients met inclusion criteria. No effect of ω-3 PUFA on ICU LOS was found (weighted mean difference WMD -2.95, 95% confidence interval, CI -10.28 to 4.39, P = 0.43). However, ω-3 PUFA reduced hospital LOS (WMD -1.37, 95% CI -2.41 to -0.33; P = 0.010) and POAF incidence (Odds Ratio OR = 0.78, 95% CI 0.68 to 0.90; P = 0.004). No effects were found on mortality or MV duration. Heterogeneity remained in subgroup analysis and we found a significant POAF reduction when ω-3 PUFA doses were administered to patients exposed to extra-corporeal circulation. Oral/enteral administration seemed to further reduce POAF. CONCLUSIONS: In patients undergoing cardiac surgery, ω-3 PUFA supplementation by oral/enteral and parenteral route reduces hospital LOS and POAF. Nonetheless considerable clinical and statistical heterogeneity weaken our findings.

Intravenous lipid emulsions in the critically ill: an update.

PURPOSE OF REVIEW: Purpose of the review is to summarize recent research addressing the role of intravenous lipid emulsions (IVLEs) in the critically ill. RECENT FINDINGS: Soybean oil-based IVLEs, which are high in the omega-6 polyunsaturated fatty acids, have been largely used in parenteral nutrition over the last several decades. However, it is now generally accepted that the higher content of phytosterols and polyunsaturated fatty acids in soybean oil IVLE may adversely affect the immunological and inflammatory status of the critically ill. In the last few years, alternative IVLEs with lower soybean oil content have been associated with important improvements in clinical outcomes, such as mortality, mechanical ventilation days, and ICU length of stay. Olive oil and fish oil IVLEs have been reported to reduce the incidence of infections, with no clear benefits in other clinical outcomes. Despite the promising results with these new parenteral nutrition strategies, the optimum composition, dosage and indication for alternative IVLEs still remain controversial. Nevertheless, according to current knowledge alternative IVLEs may be associated with improved clinical outcomes and should be considered in critically ill patients requiring parenteral nutrition. SUMMARY: There is a growing body of evidence suggesting that improved clinical outcomes can be achieved with selective use of alternative IVLEs in parenteral nutrition regimens for the critically ill. More high quality trials are needed, to better evaluate the efficacy of alternative IVLEs.

Selenium and its supplementation in cardiovascular disease--what do we know?

The trace element selenium is of high importance for many of the body's regulatory and metabolic functions. Balanced selenium levels are essential, whereas dysregulation can cause harm. A rapidly increasing number of studies characterizes the wide range of selenium dependent functions in the human body and elucidates the complex and multiple physiological and pathophysiological interactions of selenium and selenoproteins. For the majority of selenium dependent enzymes, several biological functions have already been identified, like regulation of the inflammatory response, antioxidant properties and the proliferation/differentiation of immune cells. Although the potential role of selenium in the development and progression of cardiovascular disease has been investigated for decades, both observational and interventional studies of selenium supplementation remain inconclusive and are considered in this review. This review covers current knowledge of the role of selenium and selenoproteins in the human body and its functional role in the cardiovascular system. The relationships between selenium intake/status and various health outcomes, in particular cardiomyopathy, myocardial ischemia/infarction and reperfusion injury are reviewed. We describe, in depth, selenium as a biomarker in coronary heart disease and highlight the significance of selenium supplementation for patients undergoing cardiac surgery.

Glutamine supplementation in acute pancreatitis: a meta-analysis of randomized controlled trials.

BACKGROUND: There is emerging evidence that glutamine supplementation should be considered in patients with acute and critical illness associated with a catabolic response. There are reports of glutamine supplementation in acute pancreatitis but the results of these studies are conflicting. The aim of this study was to systematically review the randomised controlled trials (RCT) of glutamine in patients with acute pancreatitis. METHODS: The Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, SCOPUS and 3 major Chinese databases were searched. The outcomes studied were mortality, total infectious complications, and length of hospital stay. A random effects model was used for meta-analysis of the outcomes in the included trials. A number of pre-specified subgroup analyses were also conducted. The summary estimates were reported as risk ratio (RR) for categorical variables and mean difference (MD) for continuous variables together with the corresponding 95% confidence interval. RESULTS: Twelve RCT that enrolled 505 patients with acute pancreatitis were included in the final analysis. Overall, glutamine supplementation resulted in a significantly reduced risk of mortality (RR 0.30; 95% CI, 0.15 to 0.60; P < 0.001) and total infectious complications (RR 0.58; 95% CI, 0.39 to 0.87; P = 0.009) but not length of hospital stay (MD -1.35; 95% CI, -3.25 to 0.56, P = 0.17). In the subgroup analyses, only patients who received parenteral nutrition and those who received glutamine in combination with other immunonutrients demonstrated a statistically significant benefit in terms of all the studied outcomes. CONCLUSIONS: This meta-analysis demonstrates a clear advantage for glutamine supplementation in patients with acute pancreatitis who receive total parenteral nutrition. Patients with acute pancreatitis who receive enteral nutrition do not require glutamine supplementation. Further studies are warranted to determine whether patients who receive combined enteral and parenteral nutrition need glutamine supplementation.

Update on antioxidant micronutrients in the critically ill.

PURPOSE OF REVIEW: To evaluate recent evidence on pharmaconutrition with antioxidant micronutrients, for different populations of adult critically ill patients. RECENT FINDINGS: Over the last few years, different studies have shown that high-dose trace elements and vitamins, especially parenteral selenium and zinc, may be able to improve relevant clinical outcomes in the most seriously ill patients. High-dose selenite monotherapy reduces mortality, particularly when a pharmacological loading dose is given in the early stage of severe sepsis and septic shock. Notwithstanding, the recently published REducing Deaths due to OXidative Stress study using an antioxidant cocktail and parenteral selenite, in addition to standard enteral nutrition, was unable to show any benefits for patients with multiple organ failure. SUMMARY: There is evidence supporting the concept of pharmaconutrition with high-dose micronutrients. Selenium therapy may be able to decrease infections and reduce mortality in sepsis, but more research is needed to better understand pharmacokinetics, optimal composition, timing, duration, and dose of antioxidant cocktails for the critically ill.

Selenium supplementation in the critically ill.

Selenium (Se) is an essential trace element with antioxidant, immunological, and anti-inflammatory properties, which are attributed to its presence in selenoproteins, as the 21st amino acid selenocysteine. These selenoenzymes are involved in redox signaling, antioxidant defense, thyroid hormone metabolism, and immune responses. Dietary intakes differ considerably between geographical regions, due to variability of the Se food content, leading to differences in dietary reference intakes and toxicity cautions. Critical illness with systemic inflammatory response syndrome (SIRS) is characterized by Se depletion with high morbidity and mortality. Se status correlates well with clinical outcome in SIRS and may be useful as an early predictor of survival. Several investigators have evaluated the benefits of Se supplementation for the critically ill, either as monotherapy or in an antioxidant micronutrient combination. Pharmaconutrition, with high-dose Se (from 500-1600 µg/d) involving an initial loading bolus, followed by continuous infusion, appears to be safe and efficacious, with evidence that it can improve clinical outcome by reducing illness severity, infectious complications, and decreasing mortality in the intensive care unit (ICU). We now have a clearer understanding of the pharmacokinetics of the initial and transient pro-oxidant effect of an intravenous bolus of selenite and the antioxidant effect of continuous infusion. Better biomarkers to ascertain optimum Se requirements for individual patients are now needed, and clinical practice guidelines need improvement. Nevertheless, sufficient evidence is available to consider initiating high-dose intravenous Se therapy routinely in critically ill SIRS patients, immediately on admission to the ICU.

Clinical and nutritional benefits of cysteine-enriched protein supplements.

PURPOSE OF REVIEW: To review recently published research into the use of dietary cysteine and/or its derivatives as functional food supplements that will enhance antioxidant status and improve outcome in certain diseases. RECENT FINDINGS: L-cysteine is now widely recognized as a conditionally essential or (indispensible) sulphur amino acid. It plays a key role in the metabolic pathways involving methionine, taurine and glutathione (GSH), and may help fight chronic inflammation by boosting antioxidant status. In stressed and inflammatory states, sulphur amino acid metabolism adapts to meet the increased requirements for cysteine as a rate-limiting substrate for GSH. Critically ill patients receiving enteral or parenteral nutrition, enriched with cysteine, exhibit decreased cysteine catabolism and improved GSH synthesis. The naturally occurring cysteine-rich proteins, whey or keratin, have the potential to be manufactured into high quality, high cysteine-containing functional foods for clinical investigation. SUMMARY: Cysteine-rich proteins, such as keratin, may have advantages over the simple amino acid or its derivatives, as nutraceuticals, to safely and beneficially improve antioxidant status in health and disease.