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.

Micronutrients early in critical illness, selective or generous, enteral or intravenous?

PURPOSE OF REVIEW: Micronutrients have essential antioxidant and immune functions, while low blood concentrations are frequently observed in critically ill patients. This has led to the concepts of complementation, repletion, or even pharmacological supplementation. Over the last three decades, many clinical studies have tested the latter strategy, with controversial or negative results. Therefore, this review aims at evaluating micronutrient-related interventions that are mandatory or need to be assessed in future trials or clinical registries in all or specific critically ill patients. RECENT FINDINGS: In the critically ill, low plasma/serum micronutrient levels not always reflect a true deficiency in the absence of demonstrable losses. Current practices of micronutrient provision and monitoring in critical care, vary substantially across the world. Also, recent clinical trials testing high dose as monotherapy (selenium, thiamine, vitamin C, vitamin D) or in combination have failed to demonstrate clinical benefits in sepsis. However, these studies have not applied a physiological integrative approach of micronutrient action. SUMMARY: Micronutrients are essential in nutrition but their administration and monitoring are difficult. So far, different well designed RCTs on intravenous and oral high dose micronutrient supplementation have been conducted. Nevertheless, very high-dose single micronutrients cannot be advocated at this stage in sepsis, or any other critical condition. By contrast, studies using combination of moderate doses of micronutrients in specific diseases, such as burns and trauma have been associated with improved outcomes. Intravenous administration seems to be the most efficient route. Future clinical trials need to integrate the physiology underlying the interconnected micronutrient activity, and choose more specific primary and secondary endpoints.

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?

Terapia nutricional en el paciente crítico con COVID-19. Una revisión / Nutritional therapy in critically ill patients with COVID-19. A case review / Terapia nutricional no paciente crítico com COVID-19. Uma revisão

Resumen: Introducción: el distrés respiratorio agudo y la falla multiorgánica que determinan admisión en una unidad de cuidados intensivos (UCI) son una causa importante de morbimortalidad en pacientes con COVID-19. Los pacientes con peores resultados clínicos -incluido una menor sobrevida en UCI- son aquellos con múltiples comorbilidades, grados variables de inmunocompromiso, adultos mayores e individuos con desnutrición previa o secundaria a la enfermedad crítica. El impacto nutricional de la enfermedad crítica sobre el músculo estriado esquelético puede exacerbarse en algunos pacientes críticamente enfermos, los infectados por SARS-CoV-2 que requieren admisión a UCI. Objetivo: proporcionar una orientación práctica de utilidad para los clínicos basados en la evidencia clínica actualizada y considerando ciertas características claves distintivas de la infección grave por SARS-CoV-2. Método: se realizó una revisión exhaustiva de la literatura científica publicada hasta abril de 2020 en idiomas español e inglés. Conclusiones: la pandemia de COVID-19 determina un desafío sin precedentes en la UCI, dado que no existen al momento medidas preventivas demostradas para evitar la evolución a la enfermedad crítica y los tratamientos curativos disponibles en esta fase de la enfermedad carecen de evidencia clínica de calidad que los sustenten. En este escenario complejo es probable que las medidas que contribuyan a potenciar el sistema inmunitario y las terapias de sostén en la UCI (incluido el soporte nutricional) sean armas sustanciales contra las infecciones graves por SARS-CoV-2; sin embargo, son necesarios más estudios en el entorno de la UCI para realizar recomendaciones específicas.

Summary Introduction: acute respiratory distress syndrome and multiple organ dysfunction, which determine admission to the ICU, are a significant cause of morbimortality in patients with COVID-19. The patients with the worst clinical outcome, including a shorter survival in the ICU, are those with multiple comorbilities, different immunocompromised states, older adults and individuals with a history of malnutrition or suffering from malnutrition secondary to a critical illness. The nutritional impact of the critical illness on the striated appearance of skeletal muscle fibers may be exacerbated in some critically ill patients who are infected with SARS-CoV-2 and need to be admitted to the ICU. Objective: this article aims to provide useful practical guidelines for clinicians based on updated clinical evidence and considering a few key characteristics that are specific to severe infection caused by SARS-Cov-2. Method: we conducted a thorough review of the scientific literature published until April 2020 in English and Spanish. Conclusions: the COVID-19 pandemic causes an unprecedented challenge in the ICU since up until today, no preventive measures have been proved successful to avoid evolution to critical illness and the therapies available for this stage of the disease are supported by quality clinical evidence. Within this complex framework we may trust that the measures that contribute to strengthening the immune system and ICU life-support therapies (including nutritional therapy) constitute essential tools to fight against severe infections caused by SARS-Cov-2. However, further studies are needed in the ICU scenario for specific recommendations to be made.

Resumo Introdução: o desconforto respiratório agudo e a falência de múltiplos órgãos que determinam a admissão na UTI são causas importantes de morbimortalidade em pacientes com COVID-19. Os pacientes com os piores resultados clínicos, incluindo menor sobrevida na UTI, são aqueles com múltiplas comorbidades, graus variáveis ??de imunocomprometimento, idosos e indivíduos com desnutrição prévia ou secundária à doença crítica. O impacto nutricional da doença crítica no músculo esquelético pode ser exacerbado em alguns pacientes graves infectados com SARS-CoV-2 que requerem internação na UTI. Objetivos: o objetivo deste artigo é fornecer orientação prática útil para os médicos baseada em evidências clínicas atualizadas e considerando certas características específicas principais da infecção grave por SARS-Cov-2. Métodos: foi realizada uma revisão exaustiva da literatura científica publicada até abril de 2020 em espanhol e inglês. Conclusões: a pandemia de COVID-19 determina um desafio sem precedentes na UTI, visto que atualmente não existem medidas preventivas comprovadas para prevenir a progressão a doença crítica e os tratamentos curativos disponíveis nesta fase da doença carecem de evidências clínicas de qualidade que os sustentem. Nesse cenário complexo, medidas que contribuem para estimular o sistema imunológico e terapias de suporte na UTI (incluindo suporte nutricional) são provavelmente armas substanciais contra infecções graves por SARS-Cov-2; no entanto, são necessários mais estudos em ambiente de UTI para fazer recomendações específicas.

Effects of glutamine supplementation on critically ill patients: Focus on efficacy and safety. An overview of systematic reviews.

OBJECTIVES: The aim of this overview of systematic reviews was to synthesize, appraise, and present all systematic review (SR) evidence on the clinical efficacy of glutamine administration to severely ill patients. METHODS: Medline, Scopus, the Cochrane Library, and Prospero were searched up to March 2020. Systematic reviews and meta-analyses of randomized controlled trials published in English, comparing immunomodulating diets-containing exclusively glutamine-with standard diets for critically ill adult patients were selected. Data were collected from each selected systematic review and all available primary studies. The primary outcome was overall mortality; secondary outcomes were rate of infectious complications, hospital and intensive care unit (ICU) length of stay (LOS). RESULTS: Seventeen SRs were eligible for inclusion. Of the SRs, 16 included meta-analyses with moderate degree of overlap (corrected covered area = 10%). These included 117 randomized controlled trials with 9933 patients. Glutamine supplementation was not associated with overall mortality and ICU LOS. However, it may reduce the rate of infectious complications overall (N = 3666, risk ratio, 0.82; 95% confidence interval [CI], 0.73-0.92; I2 = 33%: low quality of evidence). LOS was limited with the supplementation of glutamine (N = 4353 weighted mean difference, -2.90; 95% CI, -3.66 to -2.15; I2 = 81%: very low quality of evidence), but this effect was diminished when only studies with low risk for bias were synthesized. CONCLUSION: Glutamine could demonstrate a beneficial role in critical care patients of diminishing the rate of infectious complications and hospital and ICU LOS. However, future studies with better quality would confirm this finding.

Vasopressors and Nutrition Therapy: Safe Dose for the Outset of Enteral Nutrition?

BACKGROUND AND AIMS: Patients with hemodynamic instability need to receive intensive treatment as fluid replacement and vasoactive drugs. In the meantime, it is supposed to initiate nutritional therapy within 24 to 48 hours after admission to the intensive care unit (ICU), as an essential part of patient's intensive care and better outcomes. However, there are many controversies tangential to the prescription of enteral nutrition (EN) concomitant to the use of vasopressor and its doses. In this way, the present study aimed to identify what the literature presents of evidence to guide the clinical practice concerning the safe dose of vasopressors for the initiation of nutritional therapy in critically ill patients. METHODS: This review was carried out in PubMed, ProQuest, Web of Science, and Medline databases. The descriptors were used to perform the search strategy: Critical Care, Intensive Care Units, Vasoconstrictor Agents, and Enteral Nutrition. Inclusion criteria were patients of both genders, over 18 years of age, using vasoactive drugs, with the possibility of receiving EN therapy, and articles written in English, Portuguese, and Spanish. In addition, exclusion criteria were case reports, non-papers, and repeated papers. RESULTS: 10 articles met our inclusion criteria. CONCLUSION: It was observed that there are many controversies about the supply of EN in critically ill patients using vasopressor, especially about the safe dose, and it was not possible to identify a cutoff value for the beginning therapy. Despite the drug doses, clinical signs are still the most important parameters in the evaluation of EN tolerance.

Selenium in Cardiac Surgery.

Selenium (Se) is an essential trace element that plays a pivotal role in many of the body's regulatory and metabolic functions, especially during times of stress. After uptake, Se is incorporated into several Se-dependent proteins, which have potent anti-inflammatory and antioxidant capacities. Several observational clinical studies have demonstrated that Se deficiency can cause chronic cardiovascular diseases and aggravate organ dysfunction after cardiac surgery and that low levels of Se may be independently associated with the development of organ dysfunction after cardiac surgery. Based on these findings, several studies have investigated the effects of a perioperative Se supplementation strategy. Therefore, the present review describes in depth the pathophysiology and harmful stimuli during cardiac surgery, how Se may counteract these injuries, the different types of Se supplementation strategies that have been evaluated, and current evidence of its clinical significance.

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.

Vitamin D in the ICU: More sun for critically ill adult patients?

Critical illness in patients is characterized by systemic inflammation and oxidative stress. Vitamin D has a myriad of biological functions relevant to this population, including immunomodulation by the alteration of cytokine production and nuclear factor loop amplification. Low serum levels have consistently been found in observational studies conducted on critically ill patients, but the causality with mortality and worse outcomes has not been confirmed. The current focus is on interventional trials, whereas the pharmacokinetic profile of vitamin D administration remains sparse and the optimal strategy has not been confirmed. So far, high-dose oral or enteral supplementation is the most studied strategy. The largest randomized controlled trial published so far, the VITdAL-ICU (Effect of High-dose Vitamin D3 on Hospital Length of Stay in Critically Ill Patients with Vitamin D Deficiency) trial, showed no benefits on mortality in its primary analysis. However, secondary analysis suggested improvement in those patients with severe deficiency (i.e., 25-dihydroxyvitaminD <12 ng/mL). Smaller trials investigated intramuscular and intravenous administration and found interesting intermediate biochemical findings, including increased cathelicidins, but were not powered to investigate relevant clinical outcomes in the critically ill. The latest meta-analysis, which was recently published, does not support benefits of vitamin D supplementation in the heterogeneous population of critically ill patients. The European guidelines, published in the last year, suggest supplementing severely deficient patients with levels <12.5 ng/mL within the first week after ICU admission. However, other societies do not support such supplementation in their older recommendations. Large trials are currently recruiting ICU patients and could elucidate potential clinical benefits of vitamin D therapy in the critically ill.

Vitamin C Administration to the Critically Ill: A Systematic Review and Meta-Analysis.

Vitamin C, an enzyme cofactor and antioxidant, could hasten the resolution of inflammation, oxidative stress, and microvascular dysfunction. While observational studies have demonstrated that critical illness is associated with low levels of vitamin C, randomized controlled trials (RCTs) of vitamin C, alone or in combination with other antioxidants, have yielded contradicting results. We searched MEDLINE, EMBASE, CINAHL, and the Cochrane Central Register of Controlled Trials (inception to December 2017) for RCTs comparing vitamin C, by enteral or parenteral routes, with placebo or none, in intensive care unit (ICU) patients. Two independent reviewers assessed study eligibility without language restrictions and abstracted data. Overall mortality was the primary outcome; secondary outcomes were incident infections, ICU length of stay (LOS), hospital LOS, and duration of mechanical ventilation (MV). We prespecified 5 subgroups hypothesized to benefit more from vitamin C. Eleven randomized trials were included. When 9 RCTs (n = 1322) reporting mortality were pooled, vitamin C was not associated with reduced risk of mortality (risk ratio [RR] 0.72, 95% confidence interval [CI]: 0.43-1.20, P = .21). No effect was found on infections, ICU or hospital LOS, or duration of MV. In multiple subgroup comparison, no statistically significant subgroup effects were observed. However, we did observe a tendency towards a mortality reduction (RR 0.21; 95% CI: 0.04-1.05; P = .06) when intravenous high-dose vitamin C monotherapy was administered. Current evidence does not support supplementing critically ill patients with vitamin C. A moderately large treatment effect may exist, but further studies, particularly of monotherapy administration, are warranted.

Vitamin D supplementation in the critically ill: A systematic review and meta-analysis.

INTRODUCTION: Vitamin D insufficiency is reported in up to 50% of the critically ill patients and is associated with increased mortality, length of stay (LOS) in intensive care unit (ICU) and hospital, and respiratory disorders with prolonged ventilation. Benefits of vitamin D supplementation remain unclear. The aim of this systematic review was to evaluate the clinical benefits of vitamin D administration in critically ill patients. METHODS: We searched Medline, Embase, CINAHL and Cochrane database for randomized controlled trials (RCT) conducted on heterogeneous ICU patients comparing vitamin D administration to placebo. Evaluated outcomes included mortality, infectious complications, hospital/ICU LOS and length of mechanical ventilation. Two independent reviewers assessed eligibility, risk of bias and abstracted data. Data was pooled using a random effect model to estimate the risk ratio (RR) or weighted mean difference. Pre-defined subgroup analysis included oral-enteral vs. parenteral administration, high vs. low dose, vitamin d deficient patient, high vs. low quality trials. RESULTS: Six RCTs (695 patients) met study inclusion. No reduction in mortality was found (P = 0.14). No differences in ICU and hospital LOS, infection rate and ventilation days existed. In the subgroup analysis, the oral-enteral group, there was no improvement in mortality (P = 0.12) or hospital LOS (P = 0.16). Daily doses >300,000 IU did not improve mortality (P = 0.12) and ICU LOS (P = 0.12). CONCLUSIONS: In critically ill patients, Vitamin D administration does not improve clinical outcomes. The statistical imprecision could be explained by the sparse number of trials.

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.

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.

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.