Safety of a Triple-chamber Bag Parenteral Nutrition in Children Ages up to 24 Months: An Observational Study.

OBJECTIVES: Hypermagnesemia has been reported in preterm neonates treated with commercial pediatric triple-chamber bag (3CB) parenteral nutrition (PN). This postmarketing study was requested by the European Medicines Agency to assess the safety of a 3CB PN product in full-term neonates and children up to 24 months of age. METHODS: This prospective, multicenter, observational study enrolled hospitalized, full-term, newborn infants and children up to 24 months of age receiving >70% of nutrition as PN and requiring ≥50% of nutrition as PN for ≥5 days. All patients received 3CB PN during the study for ≤15 days. The primary outcome was serum magnesium, summarized by age group (0-1, >1-12, and >12-24 months). Secondary outcomes were nutritional intake and adverse events (AEs), including clinically significant abnormal laboratory results and vital signs. RESULTS: A total of 102 eligible patients were included. Median (interquartile range) parenteral magnesium intake was 0.23 (0.18-0.30) mmol ·â€Škg ·â€Šday. Mean serum magnesium showed no consistent changes during treatment in any age group. One moderate and 3 mild AEs of hypermagnesemia were reported in 4 patients (3.9%), all ages 0 to 1 month. Other AEs in >2 patients were hypertriglyceridemia (6.9%), laryngitis (3.9%), hyperkalemia, hypokalemia, hyponatremia, hypophosphatemia, and neonatal hypotension (each 2.9%). Other serum electrolytes were stable, and revealed no safety concerns. CONCLUSIONS: Mean serum magnesium levels were not affected by 3CB PN in full-term neonates and children up to 24 months of age. The risk of hypermagnesemia AEs was low when providing median parenteral magnesium of 0.2 to 0.3 mmol ·â€Škg ·â€Šday in this population.

Enteral nutrition with eicosapentaenoic acid, γ-linolenic acid and antioxidants in the early treatment of sepsis: results from a multicenter, prospective, randomized, double-blinded, controlled study: the INTERSEPT study.

INTRODUCTION: Enteral nutrition (EN) with eicosapentaenoic acid (EPA)/γ-linolenic acid (GLA) is recommended for mechanically ventilated patients with severe lung injury. EPA/GLA has anti-inflammatory benefits, as evidenced by its association with reduction in pulmonary inflammation, improvement in oxygenation and improved clinical outcomes in patients with severe forms of acute lung injury. This study was a prospective, multicenter, randomized, double-blinded, controlled trial designed to investigate whether EPA/GLA could have an effective role in the treatment of patients with early sepsis (systemic inflammatory response syndrome with confirmed or presumed infection and without any organ dysfunction) by reducing the progression of the disease to severe sepsis (sepsis associated with at least one organ failure) or septic shock (sepsis associated with hypotension despite adequate fluid resuscitation). Secondary outcomes included the development of individual organ failure, increased ICU and hospital length of stay, need for mechanical ventilation and 28-day all-cause mortality. METHODS: Randomization was concealed, and patients were allocated to receive, for seven days, either an EPA/GLA diet or an isocaloric, isonitrogenous control diet not enhanced with lipids. Patients were continuously tube-fed at a minimum of 75% of basal energy expenditure × 1.3. To evaluate the progression to severe sepsis and/or septic shock, daily screening for individual organ failure was performed. All clinical outcomes were recorded during a 28-day follow-up period. RESULTS: A total of 115 patients in the early stages of sepsis requiring EN were included, among whom 106 were considered evaluable. Intention-to-treat (ITT) analysis demonstrated that patients fed the EPA/GLA diet developed less severe sepsis and/or septic shock than patients fed the control diet (26.3% versus 50%, respectively; P = 0.0259), with similar results observed for the evaluable patients (26.4% versus 50.9% respectively; P = 0.0217). The ITT analysis demonstrated that patients in the study group developed cardiovascular failure (36.2% versus 21%, respectively; P = 0.0381) and respiratory failure (39.6% versus 24.6%, respectively; P = 0.0362) less often than the control group. Similarly, when considering only the evaluable patients, fewer patients developed cardiovascular failure (20.7% versus 37.7%, respectively; P = 0.03) and respiratory failure (26.4% versus 39.6%, respectively; P = 0.04). The percentage of patients fed the EPA/GLA diet requiring invasive mechanical ventilation was reduced compared with controls (ITT patients: 18.9% versus 33.9%, respectively; P = 0.394; evaluable patients: 17.5% versus 34.5%, respectively; P = 0.295). Patients nourished with the EPA/GLA diet remained in the ICU fewer days than the control population (ITT patients: 21.1 ICU-free days versus 14.7 ICU-free days, respectively; P < 0.0001; evaluable patients: 20.8 ICU-free days versus 14.3 ICU-free days, respectively; P < 0.0001) and fewer days at the hospital (ITT patients: 19.5 hospital-free days versus 10.3 hospital-free days, respectively; P < 0.0001; evaluable patients: 19.1 hospital-free days versus 10.2 hospital-free days, respectively; P < 0.001) (all numbers expressed as means). No significant differences in 28-day all-cause mortality were observed (ITT patients: 26.2% EPA/GLA diet versus 27.6% control diet, respectively; P = 0.72; evaluable: 26.4 EPA/GLA diet versus 30.18 control diet, respectively; P = 0.79). CONCLUSIONS: These data suggest that EPA/GLA may play a beneficial role in the treatment of enterally fed patients in the early stages of sepsis without associated organ dysfunction by contributing to slowing the progression of sepsis-related organ dysfunction, especially with regard to cardiovascular and respiratory dysfunction. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00981877.

Fish Oil-Containing Lipid Emulsions in Adult Parenteral Nutrition: A Review of the Evidence.

BACKGROUND: There is evidence from laboratory and animal studies that fish oil-containing intravenous lipid emulsions (FOC-IVLEs) have a beneficial effect on inflammation and the immune response, suggesting a possible clinical benefit. Clinical studies of FOC-IVLEs have reported mixed results. The aim of this review is to present findings from recent randomized controlled clinical trials and other quality clinical studies investigating the effects of administering intravenous fish oil alone or as part of a multilipid emulsion and to examine the quality of these studies in an objective, evidence-based manner. METHODS: Studies comparing FOC-IVLEs with other IVLEs in adults were included. Thirty-four clinical studies were evaluated: 19 investigated levels of inflammatory and immune markers as an endpoint; 13 investigated rates of infection or sepsis; 3 investigated clinical outcomes in septic patients; and 29 investigated general clinical outcomes. RESULTS: There was conflicting evidence for a beneficial effect of fish oil on levels of inflammatory and immune markers and some evidence that fish oil decreased the rate of postoperative atrial fibrillation. Studies generally reported few statistical differences in clinical outcomes and rates of infection and sepsis with FOC-IVLEs as compared with other IVLEs. The quality of reporting was generally poor, and the presented evidence for comparisons between FOC-IVLEs and other IVLEs was inconclusive or weak. CONCLUSIONS: There is very little high-quality evidence that FOC-IVLEs have a more beneficial effect than other IVLEs on clinical outcomes in adult patients.

Essential Fatty Acid Requirements and Intravenous Lipid Emulsions.

Linoleic acid (LA) and α-linolenic acid (ALA) must be supplied to the human body and are therefore considered essential fatty acids. This narrative review discusses the signs, symptoms, diagnosis, prevention, and treatment of essential fatty acid deficiency (EFAD). EFAD may occur in patients with conditions that severely limit the intake, digestion, absorption, and/or metabolism of fat. EFAD may be prevented in patients requiring parenteral nutrition by inclusion of an intravenous lipid emulsion (ILE) as a source of LA and ALA. Early ILEs consisted solely of soybean oil (SO), a good source of LA and ALA, but being rich in LA may promote the production of proinflammatory fatty acids. Subsequent ILE formulations replaced part of the SO with other fat sources to decrease the amount of proinflammatory fatty acids. Although rare, EFAD is diagnosed by an elevated triene:tetraene (T:T) ratio, which reflects increased metabolism of oleic acid to Mead acid in the absence of adequate LA and ALA. Assays for measuring fatty acids have improved over the years, and therefore it is necessary to take into account the particular assay used and its reference range when determining if the T:T ratio indicates EFAD. In patients with a high degree of suspicion for EFAD, obtaining a fatty acid profile may provide additional useful information for making a diagnosis of EFAD. In patients receiving an ILE, the T:T ratio and fatty acid profile should be interpreted in light of the fatty acid composition of the ILE to ensure accurate diagnosis of EFAD.

The use of an inflammation-modulating diet in patients with acute lung injury or acute respiratory distress syndrome: a meta-analysis of outcome data.

BACKGROUND: This meta-analysis of clinical trials compares an inflammation-modulating diet enriched with eicosapentaenoic acid (EPA), gamma-linolenic acid (GLA), and elevated antioxidants (EPA + GLA) vs a control diet to determine the effectiveness of this specialized diet on oxygenation and clinical outcomes in mechanically ventilated patients with acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). METHODS: MEDLINE, EMBASE, Cochrane Clinical Trials Register, and the U.S. National Institute of Health Clinical Trials databases were searched. The outcome measures assessed were 28-day in-hospital mortality, 28-day ventilator-free and intensive care unit (ICU)-free days, and the development of new organ failures. An evaluation of oxygenation and ventilatory variables was also performed. Outcomes were analyzed using both fixed-effects and random-effects models. RESULTS: Three randomized controlled studies (n = 411 patients) were included in this meta-analysis. Among the most important findings of this evaluation is a significant reduction in the risk of mortality (odds ratio [OR] = 0.40; 95% confidence interval [CI] = 0.24-0.68; P = .001), with significant reductions in the risk of developing new organ failures (OR = 0.17; 95% CI = 0.08-0.34; P < .0001), time on mechanical ventilation (standardized mean difference [SMD] = 0.56; 95% CI = 0.32-0.79; P < .0001), and ICU stay (SMD = 0.51; 95% CI = 0.27-0.74; P < .0001) in patients who received EPA + GLA. CONCLUSIONS: The meta-analysis showed a significant reduction in the risk of mortality as well as relevant improvements in oxygenation and clinical outcomes of ventilated patients with ALI/ARDS given EPA + GLA.

Subcutaneous Infusion of Fluids for Hydration or Nutrition: A Review.

Subcutaneous infusion, or hypodermoclysis, is a technique whereby fluids are infused into the subcutaneous space via small-gauge needles that are typically inserted into the thighs, abdomen, back, or arms. In this review, we provide an overview of the technique, summarize findings from studies that have examined the use of subcutaneous infusion of fluids for hydration or nutrition, and describe the indications, advantages, and disadvantages of subcutaneous infusion. Taken together, the available evidence suggests that, when indicated, subcutaneous infusion can be effective for administering fluids for hydration or nutrition, with minimal complications, and has similar effectiveness and safety to the intravenous route. Of note, subcutaneous infusion offers several advantages over intravenous infusion, including ease of application, low cost, and the lack of potential serious complications, particularly infections. Subcutaneous infusion may be particularly suited for patients with mild to moderate dehydration or malnutrition when oral/enteral intake is insufficient; when placement of an intravenous catheter is not possible, tolerated, or desirable; at risk of dehydration when oral intake is not tolerated; as a bridging technique in case of difficult intravenous access or catheter-related bloodstream infection while infection control treatment is being attempted; and in multiple settings (eg, emergency department, hospital, outpatient clinic, nursing home, long-term care, hospice, and home).

Safety and Efficacy of Subcutaneous Parenteral Nutrition in Older Patients: A Prospective Randomized Multicenter Clinical Trial.

BACKGROUND: Many patients who cannot tolerate adequate enteral nutrition could benefit from parenteral nutrition support but fail to receive it due to difficult intravenous (IV) access. The objective of this study was to compare the safety and efficacy of subcutaneous (SC) administration of parenteral nutrition with the peripheral IV route. MATERIALS AND METHODS: This was a prospective randomized multicenter study of 121 older hospitalized patients. The primary outcome was the composite end point of major local side effects, defined as local edema, blistering, erythema, phlebitis, cellulitis, unbearable pain, or route failure requiring a switch in route. Secondary outcomes were nutrition parameters, biochemical parameters, clinical outcomes, and safety. RESULTS: The SC route (n = 59) was noninferior to the IV route (n = 61) for major local side effects. Major local side effects trended higher in the IV group ( P = .059). Local edema was more common in the SC group ( P < .05), while route failure was more common in the IV group ( P < .001). Nutrition and biochemical parameters, safety, and clinical outcomes were similar between groups. CONCLUSIONS: The SC route of nutrient administration was better tolerated than the peripheral IV route. SC administration of parenteral nutrition represents a safe alternative to IV nutrition.

Gastrostomy tube placement in patients with advanced dementia or near end of life.

Based on current scientific literature, gastrostomy tube (G-tube) placement or other long-term enteral access devices should be withheld in patients with advanced dementia or other near end-of-life conditions. In many instances healthcare providers are not optimally equipped to implement this recommendation at the bedside. Autonomy of the patient or surrogate decision maker should be respected, as should the patient's cultural, religious, social, and emotional value system. Clinical practice needs to address risks, burdens, benefits, and expected short-term and long-term outcomes in order to clarify practice changes. This paper recommends a change in clinical practice and care strategy based on the results of a thorough literature review and provides tools for healthcare clinicians, particularly in the hospital setting, including an algorithm for decision making and a checklist to use prior to the placement of G-tubes or other long-term enteral access devices. Integrating concepts of patient-centered care, shared decision making, health literacy, and the teach-back method of education enhances the desired outcome of ethical dilemma prevention. The goal is advance care planning and a timely consensus among health team members, family members, and significant others regarding end-of-life care for patients who do not have an advance directive and lack the capacity to advocate for themselves. Achieving this goal requires interdisciplinary collaboration and proactive planning within a supportive healthcare institution environment.

Characteristics and current practice of parenteral nutrition in hospitalized patients.

BACKGROUND: For 40 years, parenteral nutrition (PN) has provided therapeutic benefits to patients unable to receive oral/enteral nutrition. Very limited published evidence exists to describe modern PN practices or characteristics of patients receiving PN. The aim of this article was to describe the characteristics of hospitalized patients receiving PN in 196 U.S. hospitals to define patient groups at risk for PN-related complications. This will provide researchers a baseline understanding about who is receiving hospital-based PN to maximize generalizability and validity of future research. METHODS: Claims data from the Premier Perspective database, the largest inpatient clinical database in the United States, were used to evaluate hospital-based PN practices. Data gathered between January 2005 and December 2007 included a total of 106,374 patients receiving PN. A total of 68,984 adults (age ≥ 18 years), 34,307 infants (age <1 year), and 3083 pediatric patients (age 1-17 years) were evaluated. Key variables such as admitting diagnosis, infection rates, in-hospital mortality, and costs were extracted. RESULTS: Hospitalized patients requiring PN in the United States are older and more often white than the overall hospitalized population. Hospitalized PN patients are more likely to be admitted emergently and have a higher severity of illness. Bloodstream infection rates in adult PN patients (25.5%) were considerably higher than in pediatric (14.7%) or neonatal patients (1.7%) receiving PN. CONCLUSIONS: These findings are the first large-scale description of "real-world" hospital-based PN practices in the United States, helping set a baseline for future PN research.

Is there a difference in bloodstream infections in critically ill patients associated with ready-to-use versus compounded parenteral nutrition?

BACKGROUND & AIMS: Parenteral nutrition is widely used in critically ill patients receiving nutritional support. Several previous studies associated the use of parenteral nutrition with the development of bloodstream infections. This study compared bloodstream infections in critical care patients receiving parenteral nutrition (PN) prepared via conventional compounding versus premixed multichamber bags. METHODS: Records in the Premier Perspective™ database for all in patients ≥ 18 years of age, with a minimum 3-day intensive care unit stay, who received PN between 2005 and 2007 were analyzed (n = 15,328). Statistical analysis of data, grouped according to preparation method, compared differences in both observed bloodstream infection rates and adjusted rates, using logistic regression to examine the impact of hospital and patient baseline characteristics. RESULTS: Patients receiving compounded parenteral nutrition had longer intensive care unit stays (11.3 vs. 9.1 days) and longer hospital stays (22.6 vs. 19.4 days); both P < .001. After adjusting for baseline differences, the probability for bloodstream infections was 19% higher when using compounded parenteral nutrition vs. multichamber bags (29.6 vs. 24.9%; odd ratio = 1.29; 95% confidence interval = 1.06-1.59). CONCLUSION: In this retrospective review of a large patient database the adjusted probability of bloodstream infection was significantly lower in patients receiving multichamber bags than compounded parenteral nutrition. These findings need to be investigated further in high quality observational studies and prospective clinical trials.

Bloodstream infections in patients receiving manufactured parenteral nutrition with vs without lipids: is the use of lipids really deleterious?

BACKGROUND: This study compared overall bacterial and bloodstream infection rates in patients receiving premixed parenteral nutrition (PN) with vs without lipid emulsion. METHODS: Data from hospitalized patients who were ≥18 years of age and receiving premixed PN between 2005 and 2007 were extracted from the Premier Perspective database. Data were categorized into 2 groups: patients who received premixed PN only and those receiving premixed PN with lipids. Multiple logistic regression was used to adjust for risk factors and potential confounders, reporting the probability of risk for an infection. RESULTS: The group without lipids was observed to have lower rates of both overall bacterial infection (43.5% vs 53.5%) and bloodstream infection (14.5% vs 18.9%). However, after adjusting for baseline characteristics, there were no significant differences in overall risk of bacterial infections (51.4% vs 53.5%; odds ratio [OR] = 1.11; 95% confidence interval [CI], 0.96-1.27) or bloodstream infections (19.6% vs 19.2%; 0.97; 0.81-1.16). In a subset of patients in the intensive care unit for ≥3 days, lower overall bacterial infection rates (58.3% vs 67.3%) and bloodstream infection rates (31.0% vs 37.0%) were observed in the group without lipids. After adjustment, there were no significant differences in risk of overall bacterial infection (OR = 0.95; 95% CI, 0.75-1.22) or bloodstream infection (0.92; 0.71-1.19) between the 2 groups. CONCLUSIONS: When administered with premixed PN, lipid emulsion was not significantly associated with an increase in the risk of infectious morbidity when compared to omitting lipids from therapy.

Bloodstream infections associated with parenteral nutrition preparation methods in the United States: a retrospective, large database analysis.

BACKGROUND: The incidence of bloodstream infection (BSI) among patients receiving parenteral nutrition (PN) is reported to vary widely from 1.3%-39%. BSI rates in a large inpatient population were compared in this study to determine if PN prepared by different methods was associated with BSI. METHODS: Data from Premier Perspective, the largest inpatient cost-based clinical and financial claims database in the United States, were analyzed. Included were all hospitalized patients age ≥18 years who received any PN from January 1, 2005, to December 31, 2007. BSI rates, the primary dependent variable, were defined as the occurrence ICD-9 codes of 038.x (septicemia), 995.91 (sepsis), 995.92 (severe sepsis), and 790.7 (bacteremia). The exposure cohort received PN in a commercial multichamber bag (MCB) (n = 4669), whereas the comparator group received PN prepared by a pharmacy (either hospital compounded or outsourced; n = 64,315). Observed data were adjusted using multivariate logistic regression for baseline differences, risk factors, and potential confounders, with propensity score matching as a sensitivity analysis. RESULTS: The observed and adjusted BSI rates indicate that MCB is associated with fewer infections than pharmacy-prepared PN (observed 17.5% vs 26.6%; adjusted 19.6% vs 25.9%, both P < .001). Propensity-matched scores found similar results with observed BSI rates of 18.9% in patients receiving MCB and 24.6% in patients receiving a compounded PN. CONCLUSION: Both the observed rate of BSI and adjusted probability of developing a BSI remained significantly lower for the MCB than the compounded PN group.

Influence of parenteral nutrition delivery system on the development of bloodstream infections in critically ill patients: an international, multicenter, prospective, open-label, controlled study--EPICOS study.

BACKGROUND: Parenteral nutrition (PN) is associated with an increased risk of developing bloodstream infections (BSIs) but the impact of the PN delivery system upon BSI rates remains unclear. This was an international, multicenter, prospective, randomized, open-label, controlled trial that investigated the differences of BSIs associated with 2 different PN systems. METHODS: Patients were randomly allocated in a 2:1:1 ratio to receive either PN delivered by a multichamber bag (MCB group), or by compounded PN made with olive oil (COM1 group) or with MCT/LCT (COM2 group). Blood cultures were performed to evaluate the incidence of BSIs, and catheter use data was collected to calculate CLAB and central venous catheter device use ratio (CVC-DUR). Secondary outcomes included the development of severe sepsis/septic shock, number of intensive care unit (ICU) and hospital days, and all-cause mortality at Day 28. RESULTS: 406 patients were included: 202 in the MCB group, 103 in the COM1 group, and 101 in the COM2 group. Baseline characteristics were well balanced between the 3 groups, BSIs were significantly higher in patients receiving compounded PN (46 BSIs for COM1+COM2 vs 34 BSIs for MCB; p = 0.03).CLAB was higher in patients receiving compounded PN (13.2 for COM1+COM2 vs 10.3 for MCB; p < 0.0001). No differences were observed for the secondary outcomes. CONCLUSION: Compounded PN was associated with a higher incidence of BSIs and CLABs, suggesting that the use of MCB PN may play a role in reducing the incidence of BSIs in patients who receive PN. TRIAL REGISTRATION NUMBER: NCT00798681.

Nutrition therapy cost analysis in the US: pre-mixed multi-chamber bag vs compounded parenteral nutrition.

BACKGROUND: Bloodstream infections (BSI) occur in up to 350 000 inpatient admissions each year in the US, with BSI rates among patients receiving parenteral nutrition (PN) varying from 1.3% to 39%. BSI-attributable costs were estimated to approximate $US12 000 per episode in 2000. While previous studies have compared the cost of different PN preparation methods, this analysis evaluates both the direct costs of PN and the treatment costs for BSI associated with different PN delivery methods to determine whether compounded or manufactured pre-mixed PN has lower overall costs. OBJECTIVE: The purpose of this study was to compare costs in the US associated with compounded PN versus pre-mixed multi-chamber bag (MCB) PN based on underlying infection risk. METHODS: Using claims information from the Premier Perspective™ database, multivariate logistic regression was used to estimate the risk of infection. A total of 44 358 hospitalized patients aged ≥18 years who received PN between 1 January 2005 and 31 December 2007 were included in the analyses. A total of 3256 patients received MCB PN and 41 102 received compounded PN. The PN-associated costs and length of stay were analysed using multivariate ordinary least squares regression models constructed to measure the impact of infectious events on total hospital costs after controlling for baseline and clinical patient characteristics. RESULTS: There were 7.3 additional hospital days attributable to BSI. After adjustment for baseline variables, the probability of developing a BSI was 30% higher in patients receiving compounded PN than in those receiving MCB PN (16.1% vs 11.3%; odds ratio = 1.56; 95% CI 1.37, 1.79; p < 0.0001), demonstrating 2172 potentially avoidable infections. The observed daily mean PN acquisition cost for patients receiving MCB PN was $US164 (including all additives and fees) compared with $US239 for patients receiving compounded PN (all differences p < 0.001). With a mean cost attributable to BSI of $US16 141, the total per-patient savings (including avoided BSI and PN costs) was $US1545. CONCLUSION: In this analysis of real-world PN use, MCB PN is associated with lower costs than compounded PN with regards to both PN acquisition and potential avoidance of BSI. Our base case indicates that $US1545 per PN patient may be saved; even if as few as 50% of PN patients are candidates for standardized pre-mix formulations, a potential savings of $US773 per patient may be realized.

Influence of tissue perfusion on the outcome of surgical patients who need blood transfusion.

PURPOSE: The aim this study was to evaluate the clinical outcome of patients needing intra-operative blood transfusion by tissue perfusion markers. METHODS: A prospective single center cohort study. Adult patients needing blood transfusion during the intra-operative period were recruited. RESULTS: This study included 61 patients. At the time of blood transfusion the hemoglobin level was 8.4+/-1.8 g/dL. Scv02 has been the best tissue perfusion marker to determine mortality, compared with hematemetric values and other tissue perfusion markers, with a cut-off point at ROC curve equal to 80% (AUC=0.75; sensitivity=80%; specificity=65.2%). Patients who received blood transfusion and had Scv02 80% (N=32), had lower mortality rates (12.5% vs. 47.1%; p=0.008) and lower incidence of postoperative complications (58.9% vs. 72.9%; p=0.06). Blood transfusion with a Scv02 80%, are associated with worse clinical outcomes.

Effects of enteral feeding with eicosapentaenoic acid, gamma-linolenic acid, and antioxidants in mechanically ventilated patients with severe sepsis and septic shock.

OBJECTIVES: Enteral diets enriched with eicosapentaenoic acid (EPA), gamma-linolenic acid (GLA), and antioxidants have previously been shown to improve outcomes in patients with acute respiratory distress syndrome. Several studies using animal models of sepsis demonstrate that enteral nutrition enriched with omega-3 fatty acids reduces mortality rate. This study investigated whether an enteral diet enriched with EPA, GLA, and antioxidant vitamins can improve outcomes and reduce 28-day all-cause mortality in patients with severe sepsis or septic shock requiring mechanical ventilation. DESIGN: Prospective, double-blind, placebo-controlled, randomized trial. SETTING: Three different intensive care units of a tertiary hospital in Brazil. PATIENTS: The study enrolled 165 patients. INTERVENTIONS: Patients were randomized to be continuously tube-fed with either a diet enriched with EPA, GLA, and elevated antioxidants or an isonitrogenous and isocaloric control diet, delivered at a constant rate to achieve a minimum of 75% of basal energy expenditure x 1.3 during a minimum of 4 days. MEASUREMENTS AND MAIN RESULTS: Patients were monitored for 28 days. Patients who were fed with the study diet experienced a significant reduction in mortality rate compared with patients fed with the control diet, the absolute mortality reduction amounting to 19.4% (p = .037). The group who received the study diet also experienced significant improvements in oxygenation status, more ventilator-free days (13.4 +/- 1.2 vs. 5.8 +/- 1.0, p < .001), more intensive care unit (ICU)-free days (10.8 +/- 1.1 vs. 4.6 +/- 0.9, p < .001), and a lesser development of new organ dysfunctions (p < .001). CONCLUSIONS: In patients with severe sepsis or septic shock and requiring mechanical ventilation and tolerating enteral nutrition, a diet enriched with EPA, GLA, and elevated antioxidants contributed to better ICU and hospital outcomes and was associated with lower mortality rates.