gamma-linolenic-acid and Respiratory-Distress-Syndrome

ARDS is an overwhelming systemic inflammatory process associated with significant morbidity and mortality. Several trials have evaluated the effects of pharmaconutrients, given as part of a feeding formula or as a nutritional supplement, on clinical outcomes in critical illness and ARDS. The aim of this review is to assess the effects of immunonutrition on mechanically ventilated adults with ARDS compared to the standard feeding formula.. We searched MEDLINE, EMBASE, CENTRAL, conference proceedings, and trial registries for appropriate studies up to April 2018. We performed statistical analysis according to Cochrane methodological standards. We used the GRADE approach to assess the quality of evidence for each outcome.. We identified 10 randomized controlled trials with 1,015 participants. All of the studies compared an enteral formula or additional supplemental omega-3 fatty acids (eg, eicosapentaenoic acid, docosahexaenoic acid), γ-linolenic acid, and antioxidants. All of the studies reported mortality. For the primary outcome, there was no difference in all-cause mortality (for the longest period reported) with the use of an immunonutrition enteral formula or additional supplements of omega-3 fatty acids, γ-linolenic acid, and antioxidants (risk ratio = 0.79, 95% CI 0.59-1.07; low-quality evidence). For the secondary outcomes, we are uncertain whether immunonutrition with omega-3 fatty acids and antioxidants improves ICU length of stay, ventilator days, and oxygenation or increases harm.. This Cochrane meta-analysis of 10 studies of varying quality examined the effects of omega-3 fatty acids and antioxidants in adults with ARDS. This intervention may produce little or no difference in all-cause mortality between groups. We are uncertain whether immunonutrition with omega-3 fatty acids and antioxidants improves ventilator days, ICU length of stay, or oxygenation due to the very low quality of evidence.

Topics: Antioxidants; Cause of Death; Dietary Supplements; Docosahexaenoic Acids; Eicosapentaenoic Acid; Enteral Nutrition; Fatty Acids, Omega-3; gamma-Linolenic Acid; Humans; Randomized Controlled Trials as Topic; Respiration, Artificial; Respiratory Distress Syndrome

Acute respiratory distress syndrome (ARDS) is an overwhelming systemic inflammatory process associated with significant morbidity and mortality. Pharmacotherapies that moderate inflammation in ARDS are lacking. Several trials have evaluated the effects of pharmaconutrients, given as part of a feeding formula or as a nutritional supplement, on clinical outcomes in critical illness and ARDS.. To systematically review and critically appraise available evidence on the effects of immunonutrition compared to standard non-immunonutrition formula feeding on mechanically ventilated adults (aged 18 years or older) with acute respiratory distress syndrome (ARDS).. We searched MEDLINE, Embase, CENTRAL, conference proceedings, and trial registries for appropriate studies up to 25 April 2018. We checked the references from published studies and reviews on this topic for potentially eligible studies.. We included all randomized controlled trials (RCTs) and quasi-randomized controlled trials comparing immunonutrition versus a control or placebo nutritional formula in adults (aged 18 years or older) with ARDS, as defined by the Berlin definition of ARDS or, for older studies, by the American-European Consensus Criteria for both ARDS and acute lung injury.. Two review authors independently assessed the quality of studies and extracted data from the included trials. We sought additional information from study authors. We performed statistical analysis according to Cochrane methodological standards. Our primary outcome was all-cause mortality. Secondary outcomes included intensive care unit (ICU) length of stay, ventilator days, indices of oxygenation, cardiac adverse events, gastrointestinal adverse events, and total number of adverse events. We used GRADE to assess the quality of evidence for each outcome.. We identified 10 randomized controlled trials with 1015 participants. All studies compared an enteral formula or additional supplemental omega-3 fatty acids (i.e. eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA)), gamma-linolenic acid (GLA), and antioxidants. We assessed some of the included studies as having high risk of bias due to methodological shortcomings. Studies were heterogenous in nature and varied in several ways, including type and duration of interventions given, calorific targets, and reported outcomes. All studies reported mortality. For the primary outcome, study authors reported no differences in all-cause mortality (longest period reported) with the use of an immunonutrition enteral formula or additional supplements of omega-3 fatty acids and antioxidants (risk ratio (RR) 0.79, 95% confidence interval (CI) 0.59 to 1.07; participants = 1015; studies = 10; low-quality evidence).For secondary outcomes, we are uncertain whether immunonutrition with omega-3 fatty acids and antioxidants reduces ICU length of stay (mean difference (MD) -3.09 days. 95% CI -5.19 to -0.99; participants = 639; studies = 8; very low-quality evidence) and ventilator days (MD -2.24 days, 95% CI -3.77 to -0.71; participants = 581; studies = 7; very low-quality evidence). We are also uncertain whether omega-3 fatty acids and antioxidants improve oxygenation, defined as ratio of partial pressure of arterial oxygen (PaO₂) to fraction of inspired oxygen (FiO₂), at day 4 (MD 39 mmHg, 95% CI 10.75 to 67.02; participants = 676; studies = 8), or whether they increase adverse events such as cardiac events (RR 0.87, 95% CI 0.09 to 8.46; participants = 339; studies = 3; very low-quality evidence), gastrointestinal events (RR 1.11, 95% CI 0.71 to 1.75; participants = 427; studies = 4; very low-quality evidence), or total adverse events (RR 0.91, 95% CI 0.67 to 1.23; participants = 517; studies = 5; very low-quality evidence).. This meta-analysis of 10 studies of varying quality examined effects of omega-3 fatty acids and/or antioxidants in adults with ARDS. This intervention may produce little or no difference in all-cause mortality between groups. We are uncertain whether immunonutrition with omega-3 fatty acids and antioxidants improves the duration of ventilator days and ICU length of stay or oxygenation at day 4 due to the very low quality of evidence. Adverse events associated with immunonutrition are also uncertain, as confidence intervals include the potential for increased cardiac, gastrointestinal, and total adverse events.

Topics: Adult; Antioxidants; Cause of Death; Docosahexaenoic Acids; Eicosapentaenoic Acid; Enteral Nutrition; Fatty Acids, Omega-3; gamma-Linolenic Acid; Humans; Intensive Care Units; Length of Stay; Oxygen Inhalation Therapy; Randomized Controlled Trials as Topic; Respiration, Artificial; Respiratory Distress Syndrome

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.. 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 PaO. Twelve RCTs (n = 1280 patients) met our inclusion criteria. Omega-3 PUFAs administration was associated with a significant improvement in early PaO. In critically ill patients with ARDS, ω-3 PUFAs in enteral immunomodulatory diets may be associated with an improvement in early and late PaO

Topics: Antioxidants; Critical Illness; Eicosapentaenoic Acid; Enteral Nutrition; Fatty Acids, Omega-3; gamma-Linolenic Acid; Humans; Immunomodulation; Length of Stay; Randomized Controlled Trials as Topic; Respiration, Artificial; Respiratory Distress Syndrome; Treatment Outcome

Omega-3 fatty acids contained in fish oils have shown efficacy in the treatment of chronic and acute inflammatory diseases due to their pleiotropic effects on inflammatory cell signalling pathways. In a variety of experimental and clinical studies, omega-3 fatty acids attenuated hyperinflammatory conditions and induced faster recovery. This chapter will shed light on the effects of intravenous fish oil in adult intensive care unit (ICU) patients and will discuss clinical data and recent meta-analyses on the topic. While significant beneficial effects on infection rates and the lengths of ICU and hospital stays have concordantly been identified in three recent meta-analyses on non-ICU surgical patients, the level of evidence is not so clear for critically ill patients. Three meta-analyses published in 2012 or 2013 explored data on the ICU population. Although the present data suggest the consideration of enteral nutrition enriched with fish oil, borage oil and antioxidants in mild to severe acute respiratory distress syndrome, only one of the three meta-analyses found a trend (p = 0.08) of lower mortality in ICU patients receiving intravenous omega-3 fatty acids. Two of the meta-analyses indicated a significantly shorter hospital stay (5.17-9.49 days), and one meta-analysis found a significant reduction in ICU days (1.92). As a result of these effects, cost savings were postulated. Unlike in surgical patients, the effects of fish oil on infection rates were not found to be statistically significant in ICU patients, and dose-effect relationships were not established for any cohort. Thus, obvious positive secondary outcome effects with intravenous fish oil have not yet been shown to transfer to lower mortality in critically ill patients. There is a need for adequately powered, well-planned and well-conducted randomized trials to give clear recommendations on the individual utility and dosage of intravenous omega-3 fatty acids in critical illness.

Topics: Administration, Intravenous; Adult; Antioxidants; Critical Illness; Enteral Nutrition; Fat Emulsions, Intravenous; Fatty Acids, Omega-3; Fish Oils; gamma-Linolenic Acid; Humans; Intensive Care Units; Length of Stay; Meta-Analysis as Topic; Plant Oils; Respiratory Distress Syndrome

Enteral immunomodulatory nutrition is considered as a promising therapy for the treatment of acute lung injury and acute respiratory distress syndrome (ALI/ARDS). However, there are still some divergences, and it is unclear whether this treatment should be recommended for patients with ALI/ARDS. Therefore, we conducted this systematic review and meta-analysis to assess the efficacy and safety of an enteral immunomodulatory diet on the clinical outcomes of ALI/ARDS patients.. We retrieved potentially relevant clinical trials though electronic databases. All trials of enteral immunomodulatory diet for ALI/ARDS were included. Analyses of the overall all-cause mortality, 28-day ventilator-free days and 28-day intensive care unit (ICU) free days were conducted.. In total six controlled trials were evaluated. The pooled results did not show a significant reduction in the risk of all-cause mortality (M-H RR (the overall Mantel-Haenszel relative risk), 0.81 (95% CI, 0.50-1.31); p = 0.38; 6 trials, n = 717) in ALI/ARDS patients treated with the immunomodulatory diet. This treatment also did not extend the ventilator-free days and ICU-free days. However, patients with high mortality might benefit from this treatment.. The enteral immunomodulatory diet could not reduce the severity of the patients with ALI/ARDS. Whereas, for ALI/ARDS patients with high mortality, this treatment might reduce the all-cause mortality, but its use should be treated with discretion.

Topics: Acute Lung Injury; Antioxidants; Dietary Fats; Enteral Nutrition; gamma-Linolenic Acid; Humans; Respiratory Distress Syndrome

Acute respiratory distress syndrome (ARDS) is defined as the acute onset of noncardiogenic edema and subsequent gas-exchange impairment due to a severe inflammatory process. Recent report on the prognostic value of eicosanoids in patients with ARDS suggests that modulating the inflammatory response through the use of polyunsaturated fatty acids may be a useful strategy for ARDS treatment. The use of enteral diets enriched with eicosapentaenoic acid (EPA) and gamma-linolenic acid (GLA) has reported promising results, showing an improvement in respiratory variables and haemodynamics. However, the interpretation of the studies is limited by their heterogeneity and methodology and the effect of ω-3 fatty acid-enriched lipid emulsion or enteral diets on patients with ARDS remains unclear. Therefore, the routine use of ω-3 fatty acid-enriched nutrition cannot be recommended and further large, homogeneous, and high-quality clinical trials need to be conducted to clarify the effectiveness of ω-3 polyunsaturated fatty acids.

Topics: Antioxidants; Eicosapentaenoic Acid; Fatty Acids, Omega-3; gamma-Linolenic Acid; Hemodynamics; Humans; Respiratory Distress Syndrome

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are among the most frequent etiologies for admission to the intensive care unit. These patients are at a high risk of malnutrition due to hypercatabolism caused by inflammation, drugs, and de-conditioning. Nutrition should support minimizing the loss of lean body mass and accurately meet energy demands. Additional use of omega-3 fatty acid, γ-linolenic acid, and antioxidant-enriched diets has been suggested in recent years as a tool to improve outcome in ALI/ARDS patients. More recent findings have taught us that too much of these supplements are detrimental and that the bolus administration may not be as efficient as continuous administration.

Topics: Acute Lung Injury; Administration, Intravenous; Animals; Antioxidants; Critical Illness; Dietary Supplements; Disease Models, Animal; Fatty Acids, Omega-3; Fish Oils; gamma-Linolenic Acid; Humans; Nutritional Support; Randomized Controlled Trials as Topic; Respiratory Distress Syndrome

With a high rate of mortality, acute respiratory distress syndrome (ARDS) has limited treatments options. Immune-enhanced formulas, containing eicosapentaenoic acid, borage oil, and antioxidants, have shown to be beneficial in adults patients with ARDS, decreasing mortality, length of mechanical ventilation, and new organ dysfunction. There is promising research in pediatric patients with improvement in oxygenation status found, but further trials are needed to realize these benefits in pediatric and infant populations.

Topics: Adult; Antioxidants; Child; Eicosapentaenoic Acid; gamma-Linolenic Acid; Humans; Infant; Nutritional Support; Plant Oils; Respiratory Distress Syndrome

Enteral nutrition is increasingly becoming the standard of care for critically ill patients with the goal of providing nutritional support that prevents nutritional deficiencies and reduces morbidity. Furthermore, the development of nutritional strategies that dampen inflammation is an encouraging advance in the management of patients who have acute respiratory distress syndrome. This article discusses evidence from randomized, controlled studies that the use of a specialized nutritional formula containing eicosapentaenoic acid plus gamma-linolenic acid and elevated antioxidants offer physiologic and anti-inflammatory benefits over standard formulas.

Topics: Animals; Clinical Trials as Topic; Eicosapentaenoic Acid; Enteral Nutrition; Fatty Acids, Unsaturated; gamma-Linolenic Acid; Humans; Morbidity; Oxygen; Respiratory Distress Syndrome

Topics: Amino Acids; Arachidonic Acids; gamma-Linolenic Acid; Humans; Nutritional Support; Respiratory Distress Syndrome

Respiratory failure caused by acute lung injury or acute respiratory distress syndrome is associated with significant morbidity in children. Enteral nutrition enriched with eicosapentaenoic acid, γ-linolenic acid and antioxidants (eicosapentaenoic acid + γ-linolenic acid) can safely modulate plasma phospholipid fatty acid profiles, reduce inflammation, and improve clinical outcomes in adults. There is little information regarding the use of enteral eicosapentaenoic acid + γ-linolenic acid to modulate plasma phospholipid fatty acid profiles in children. We sought to determine if continuous feeding of enteral nutrition containing eicosapentaenoic acid, γ-linolenic acid, and antioxidants was feasible in critically ill children with acute lung injury or acute respiratory distress syndrome. We further evaluated the impact of such an approach on the alteration of plasma phospholipid fatty acid concentrations.. Prospective, blinded, randomized, controlled, multicenter trial.. PICU.. Twenty-six critically ill children (age 6.2 ± 0.9 yr, PaO2/FIO2 185 ± 15) with the diagnosis of acute lung injury or acute respiratory distress syndrome.. Mechanically ventilated children received either eicosapentaenoic acid + γ-linolenic acid or a standard pediatric enteral formula. Clinical, biochemical, plasma fatty acid, and safety data were assessed at baseline, study days 4 and 7.. At baseline, there were no significant differences in the two study groups. Both groups met enteral feeding goals within 30 hrs and had similar caloric delivery. There were no differences in formula tolerance as measured by serum chemistries, liver and renal function, and hematology studies after 7 days of feeding either eicosapentaenoic acid + γ-linolenic acid or pediatric enteral formula. On study day 4 and 7, plasma phospholipid fatty acid profiles in the eicosapentaenoic acid + γ-linolenic acid group showed a significant increase in anti-inflammatory circulating markers.. Providing enteral nutrition with eicosapentaenoic acid + γ-linolenic acid to critically ill children with lung injury was feasible and caloric goals were met within 30 hrs. This feeding protocol effectively modulated plasma phospholipid fatty acid concentrations to reflect an anti-inflammatory profile. This study provides data to inform future outcome studies using enteral eicosapentaenoic acid + γ-linolenic acid in children with lung injury.

Topics: 8,11,14-Eicosatrienoic Acid; Acute Lung Injury; Antioxidants; Arachidonic Acid; Biomarkers; Child; Child, Preschool; Dietary Supplements; Double-Blind Method; Eicosapentaenoic Acid; Energy Intake; Enteral Nutrition; Feasibility Studies; Female; Food, Formulated; gamma-Linolenic Acid; Humans; Immunomodulation; Male; Respiration, Artificial; Respiratory Distress Syndrome

To assess the effect of an enteral diet enriched with eicosapentaenoic acid (EPA), gamma-linolenic acid (GLA), and anti-oxidants on the incidence of organ dysfunction and nosocomial infections in septic patients with acute lung injury or acute respiratory distress syndrome (ARDS) compared with a standard enteral diet.. This prospective, randomized, open-label study was performed in 11 Spanish intensive care units (ICU). Adult patients with sepsis and acute lung injury or ARDS were randomly allocated to receive either an EPA-GLA diet or a control diet.. Of the 198 patients that were eligible, 160 were randomized and 132 were studied. Patient demographics, APACHE II and SOFA scores, and nutritional variables on admission were similar between the EPA-GLA diet and control diet groups. The EPA-GLA diet group showed a trend toward a decreased SOFA score, but it was not significant. No differences were observed in the PaO(2)/FiO(2) ratio or the days on mechanical ventilation between the groups. Incidence of infections was similar in the groups. The control group stayed longer in the ICU than the EPA-GLA diet group (16 vs. 18; p = 0.02).. A diet enriched with EPA, GLA, and anti-oxidants does not improve gas exchange or decrease the incidence of novel organ failures in critically ill septic patients with acute lung injury or ARDS. Patients treated with the EPA-GLA diet stayed in the ICU for less time, but we did not find any differences in infectious complications.

Topics: Acute Lung Injury; Adult; Aged; Antioxidants; Cross Infection; Eicosapentaenoic Acid; Enteral Nutrition; Female; Food, Formulated; gamma-Linolenic Acid; Humans; Incidence; Intensive Care Units; Intention to Treat Analysis; Length of Stay; Male; Middle Aged; Multiple Organ Failure; Respiration, Artificial; Respiratory Distress Syndrome; Sepsis; Spain

To explore the effects of an enteral diet enriched with eicosapentaenoic acid (EPA), gamma-linolenic acid (GLA), and antioxidants on the respiratory profile and outcome of patients with acute lung injury.. Single-center, prospective, randomized, controlled, unblinded study.. General intensive care department of a tertiary-care, university-affiliated hospital.. A total of 100 patients with acute lung injury, diagnosed according to the American-European Consensus Conference on ARDS.. Patients were randomized to receive the standard isonitrogenous, isocaloric enteral diet or the standard diet supplemented with EPA and GLA for 14 days.. Patient demographics, Acute Physiology and Chronic Health Evaluation II score, and type of admission were noted at admission. Compared with baseline oxygenation (EPA + GLA group vs. control group), by days 4 and 7, patients receiving the EPA + GLA diet showed significant improvement in oxygenation (PaO(2)/FIO(2), 317.3 +/- 99.5 vs. 214.3 +/- 56.4 and 296.5 +/- 165.3 vs. 236.3 +/- 79.8, respectively; p < .05). Compliance was significantly higher in the EPA + GLA group observed at day 7 (55.1 +/- 46.5 vs. 35.2 +/- 20.0 mL/mbar, p < .05). No significant difference was found in nutritional variables. Resting energy expenditure was significantly higher in patients in the EPA + GLA group, but their body mass index was also higher (p < .05). A significant difference was found in length of ventilation (p < .04) in favor of the EPA + GLA group. There was no between-group difference in survival.. In patients with acute lung injury, a diet enriched with EPA + GLA may be beneficial for gas exchange, respiratory dynamics, and requirements for mechanical ventilation.

Topics: Adult; Eicosapentaenoic Acid; Enteral Nutrition; Female; gamma-Linolenic Acid; Humans; Male; Middle Aged; Prospective Studies; Respiration, Artificial; Respiratory Distress Syndrome; Treatment Outcome

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.. Prospective, double-blind, placebo-controlled, randomized trial.. Three different intensive care units of a tertiary hospital in Brazil.. The study enrolled 165 patients.. 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.. 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).. 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.

Topics: Aged; Antioxidants; Ascorbic Acid; Brazil; Double-Blind Method; Eicosapentaenoic Acid; Enteral Nutrition; Female; gamma-Linolenic Acid; Humans; Intensive Care Units; Length of Stay; Male; Middle Aged; Multiple Organ Failure; Prospective Studies; Pulmonary Gas Exchange; Respiration, Artificial; Respiratory Distress Syndrome; Sepsis; Shock, Septic; Vitamin E

Previously, we showed that acute respiratory distress syndrome patients fed an enteral diet containing eicosapentaenoic acid and gamma-linolenic acid and elevated antioxidants (EPA+GLA; Oxepa) had significantly reduced pulmonary inflammation, increased oxygenation, and improved clinical outcomes. In a subset of acute respiratory distress syndrome patients from this trial, we performed a preliminary examination of the potential mechanisms underlying these clinical improvements by retrospectively testing the hypothesis that enteral feeding with EPA+GLA could reduce alveolar-capillary membrane protein permeability and the production of interleukin (IL)-8, IL-6, tumor necrosis factor-alpha, and leukotriene B4 that are responsible, in part, for pulmonary inflammation.. Prospective, randomized, double-blind, controlled clinical trial.. Intensive Care Unit of the Ohio State University Medical Center.. A total of 67 patients were enrolled who met defined criteria for acute lung injury/acute respiratory distress syndrome.. A total of 43 of 67 evaluable patients randomly received either EPA+GLA or an isonitrogenous, isocaloric standard diet that was tube fed at a minimum caloric delivery of 75% of basal energy expenditure times 1.33 for at least 4 to 7 days.. Bronchoalveolar lavage (BAL) was performed at baseline and study days 4 and 7 to obtain BAL fluid (BALF) for measurement of total protein, ceruloplasmin, and transferrin, total neutrophil count, IL-8, IL-6, tumor necrosis factor-alpha, and leukotriene B4. Oxygenation, measured as Pao2/Fio2, was assessed before BAL. Patients fed EPA+GLA had a significant reduction in BALF ceruloplasmin and IL-8 during the study as compared with patients fed the control diet. BALF levels of total protein, neutrophils, and leukotriene B4 tended to decrease in EPA+GLA patients over the course of the study as compared with control patients. BALF levels of IL-6 declined similarly during the study in both groups. A trend toward a reduction in BALF tumor necrosis factor-alpha was observed on study day 7 in the EPA+GLA group as compared with control patients. Significant improvements in oxygenation (Pao2/Fio2) occurred in EPA+GLA patients on study day 4 as compared with controls. Correlation analysis revealed significant relationships between BALF neutrophil counts and indices of alveolar-capillary membrane protein permeability, IL-8, and leukotriene B4.. This preliminary investigation showing a decrease in BALF levels of IL-8 and leukotriene B4 and the associated reduction of BALF neutrophils and alveolar membrane protein permeability in acute respiratory distress syndrome patients fed EPA+GLA support, in part, the potential mechanisms underlying the previously described clinical improvements with this diet. Additional controlled studies are needed to confirm these findings.

Topics: Antioxidants; Double-Blind Method; Eicosapentaenoic Acid; Enteral Nutrition; Female; gamma-Linolenic Acid; Humans; Inflammation Mediators; Male; Middle Aged; Prospective Studies; Proteins; Pulmonary Alveoli; Respiratory Distress Syndrome

Recent studies in animal models of sepsis-induced acute respiratory distress syndrome (ARDS) have shown that a low-carbohydrate, high-fat diet combining the anti-inflammatory and vasodilatory properties of eicosapentaenoic acid (EPA; fish oil), gamma-linolenic acid (GLA; borage oil) (EPA+GLA), and antioxidants improves lung microvascular permeability, oxygenation, and cardiopulmonary function and reduces proinflammatory eicosanoid synthesis and lung inflammation. These findings suggest that enteral nutrition with EPA+GLA and antioxidants may reduce pulmonary inflammation and may improve oxygenation and clinical outcomes in patients with ARDS.. Prospective, multicentered, double-blind, randomized controlled trial.. Intensive care units of five academic and teaching hospitals in the United States.. We enrolled 146 patients with ARDS (as defined by the American-European Consensus Conference) caused by sepsis/pneumonia, trauma, or aspiration injury in the study.. Patients meeting entry criteria were randomized and continuously tube-fed either EPA+GLA or an isonitrogenous, isocaloric standard diet at a minimum caloric delivery of 75% of basal energy expenditure x 1.3 for at least 4-7 days.. Arterial blood gases were measured, and ventilator settings were recorded at baseline and study days 4 and 7 to enable calculation of PaO2/FIO2, a measure of gas exchange. Pulmonary neutrophil recruitment was assessed by measuring the number of neutrophils and the total cell count in bronchoalveolar lavage fluid at the same time points. Clinical outcomes were recorded. Baseline characteristics of 98 evaluable patients revealed that key demographic, physiologic, and ventilatory variables were similar at entry between both groups. Multiple bronchoalveolar lavages revealed significant decreases (approximately 2.5-fold) in the number of total cells and neutrophils per mL of recovered lavage fluid during the study with EPA+GLA compared with patients fed the control diet. Significant improvements in oxygenation (PaO2/FIO2) from baseline to study days 4 and 7 with lower ventilation variables (FIO2, positive end-expiratory pressure, and minute ventilation) occurred in patients fed EPA+GLA compared with controls. Patients fed EPA+GLA required significantly fewer days of ventilatory support (11 vs. 16.3 days; p = .011), and had a decreased length of stay in the intensive care unit (12.8 vs. 17.5 days; p = .016) compared with controls. Only four of 51 (8%) patients fed EPA+GLA vs. 13 of 47 (28%) control patients developed a new organ failure during the study (p = .015).. The beneficial effects of the EPA+GLA diet on pulmonary neutrophil recruitment, gas exchange, requirement for mechanical ventilation, length of intensive care unit stay, and the reduction of new organ failures suggest that this enteral nutrition formula would be a useful adjuvant therapy in the clinical management of patients with or at risk of developing ARDS.

Topics: Antioxidants; Blood Gas Analysis; Bronchoalveolar Lavage Fluid; Double-Blind Method; Eicosapentaenoic Acid; Enteral Nutrition; Female; gamma-Linolenic Acid; Humans; Inflammation; Length of Stay; Leukocyte Count; Male; Middle Aged; Neutrophils; Prospective Studies; Pulmonary Gas Exchange; Pulmonary Ventilation; Respiration, Artificial; Respiratory Distress Syndrome

Acute respiratory distress syndrome (ARDS) is a life-threatening condition in which the lungs become severely inflamed, causing the alveoli to constrict or fill with fluid, which prevents the lungs from functioning properly. This disease becomes more dangerous when it occurs in patients with diabetes. Because of the clinical condition of these patients, it is not possible to treat them with usual medicines. One of the best options for treating these people is to use herbs. Borage (Borago officinalis) is a medicinal herb that, in addition to its anti-inflammatory properties, is also able to control blood sugar. Therefore, in the current study, the effect of borage oil was considered on the signaling pathway of the NLRP3 inflammasome complex, TLR4, and serum levels of inflammatory cytokines (IL-1? and IL-18) in type II diabetic patients with ARDS. For this purpose, 25 diabetic type II patients with ARDS were divided into three groups by ARDS Berlin Definition. Then, after providing the demographic and clinical characteristics of the patients, they were treated with 30 mg/day borage oil for seven days. The expression of NLRP3 and TLR4 genes (by Real-time PCR technique) and serum levels of IL-1? and IL-18 (by ELISA test) were evaluated before and after treatment with borage oil through blood samples taken from patients. The results showed that serum levels of inflammatory cytokines (IL-1? and IL-18), NLRP3 gene, and TLR4 gene were significantly decreased in diabetic type II patients with mild ARDS by treating with borage oil. IL-1? serum level and TLR4 were significantly decreased in diabetic type II patients with moderate ARDS. But there was not any significant decrease or increase in IL-1?, IL-18, NLRP3 gene, and TLR4 gene in diabetic type II patients with severe ARDS after 7 days of treatment with borage oil. According to the obtained results, borage oil can act as a double-edged blade. Thus, in the early and middle stages of ARDS, borage oil can be effective in reducing the inflammasome pathway of inflammation and also reduce blood sugar levels in these diabetic patients. But in the severe stage of ARDS, it not only does not help to treat the ARDS; it also increases systolic and diastolic blood pressure in diabetic patients.

Topics: Aged; Anti-Inflammatory Agents; Blood Glucose; Borago; Cytokines; Diabetes Mellitus, Type 2; Enzyme-Linked Immunosorbent Assay; Female; gamma-Linolenic Acid; Gene Expression; Humans; Inflammasomes; Inflammation Mediators; Interleukin-18; Interleukin-1beta; Male; Middle Aged; NLR Family, Pyrin Domain-Containing 3 Protein; Plant Oils; Respiratory Distress Syndrome; Reverse Transcriptase Polymerase Chain Reaction; Signal Transduction; Toll-Like Receptor 4

Topics: Antioxidants; Critical Care; Eicosapentaenoic Acid; Enteral Nutrition; gamma-Linolenic Acid; Hospital Mortality; Humans; Nutritional Status; Respiration, Artificial; Respiratory Distress Syndrome; Shock, Septic; Survival Rate; Systemic Inflammatory Response Syndrome

Topics: Antioxidants; Eicosapentaenoic Acid; Enteral Nutrition; gamma-Linolenic Acid; Humans; Respiratory Distress Syndrome

Topics: Antioxidants; Eicosapentaenoic Acid; Enteral Nutrition; gamma-Linolenic Acid; Humans; Intensive Care Units; Multiple Organ Failure; Pulmonary Gas Exchange; Respiratory Distress Syndrome; Sepsis; Shock, Septic

Oxygen free radicals are important mediators of both physiological and pathological events. In acute lung injury, the activated lymphocytes stimulate tumor necrosis factor (TNF) and other cytokines. These lymphokines augment free radical generation by polymorphonuclear leukocytes (PMNLs), macrophages and other cells which may ultimately produce acute respiratory distress syndrome (ARDS). This is supported by our results presented here in that there is a significant increase in lipid peroxidation products in patients with established ARDS. The amount of lipid peroxidation was significantly higher in the established ARDS group compared to patients who are at risk for ARDS. Nitric oxide concentrations were significantly decreased in established ARDS compared to the control and those who are at risk for ARDS. Fatty acid analysis of the plasma phospholipid fraction revealed a significant decreased in linoleic acid, gamma-linolenic acid, dihomo-gamma-linolenic acid and arachidonic acid levels of n-6 series and alpha-linolenic acid, eicosapentaenoic acid, docosa-hexanenoic acid of n-3 series. Patients who are at risk for ARDS have decreased levels of gamma-linolenic acid of the n-6 series, alpha-linolenic acid and eicosapentaenoic acid of the n-3 series. These results suggest that lipid peroxides and alteration in essential fatty acid metabolism may have a role in the pathogenesis of ARDS.

Topics: alpha-Linolenic Acid; Arachidonic Acid; Docosahexaenoic Acids; Eicosapentaenoic Acid; Fatty Acids, Essential; gamma-Linolenic Acid; Humans; Linoleic Acid; Lipid Peroxidation; Malondialdehyde; Nitric Oxide; Nitrites; Oleic Acid; Oxidative Stress; Respiratory Distress Syndrome; Risk Factors; Thiobarbituric Acid Reactive Substances

Because vasoactive eicosanoids derived from arachidonic acid present in immune cell phospholipids promote lung inflammation in critically ill patients, novel experimental diets containing eicosapentaenoic acid from fish oil and gamma-linolenic acid from borage oil have been designed to limit arachidonic acid metabolism. However, excess dietary eicosapentaenoic acid impairs superoxide formation and bacterial killing by immune cells. The present study determined whether short-term enteral feeding with diets enriched with either eicosapentaenoic acid alone or in combination with gamma-linolenic acid would modulate alveolar macrophage eicosanoid synthesis without compromising bactericidal function.. Prospective, randomized, controlled, blinded study.. University medical center.. Adult male Sprague-Dawley rats.. Rats underwent surgical placement of a gastroduodenal feeding catheter and were randomly assigned to receive one of three high-fat (55.2% of total calories), low-carbohydrate diets containing isocaloric amounts of lipids for 4 days. The control diet was enriched with linoleic acid, whereas the two test diets were low in linoleic acid and enriched with either 5 mole % eicosapentaenoic acid alone or in combination with 5 mole % gamma-linolenic acid. Alveolar macrophages were then procured to assess phospholipid fatty acid composition, eicosanoid synthesis after stimulation with endotoxin, superoxide formation and phagocytosis by flow cytometry, and killing of Staphylococcus aureus. Alveolar macrophage levels of arachidonic acid were significantly (p < .01) lower and levels of eicosapentaenoic and dihomo-gamma-linolenic acids were higher after feeding the eicosapentaenoic and gamma-linolenic acid diet vs. the linoleic acid diet. Ratios of thromboxane B2,/B3, leukotriene B4/B5, and prostaglandin E2/E1 were reduced in the macrophages from rats given either the eicosapentaenoic acid or eicosapentaenoic acid with gamma-linolenic acid diet compared with ratios from rats given the linoleic acid diet. Macrophages from rats given the eicosapentaenoic with gamma-linolenic acid diet released 35% or 24% more prostaglandin E1 than macrophages from rats given either the linoleic acid or the eicosapentaenoic acid diet, respectively. Macrophage superoxide generation, phagocytosis of opsonized zymosan, and killing of S. aureus were similar irrespective of dietary treatment.. Short-term enteral feeding with an eicosapentaenoic acid-enriched or eicosapentaenoic with gamma-linolenic acid-enriched diet rapidly modulated the fatty acid composition of alveolar macrophage phospholipids, promoted a shift toward formation of less inflammatory eicosanoids by stimulated macrophages, but did not impair alveolar macrophage bactericidal function relative to responses observed after feeding a linoleic acid diet.

Topics: Animals; Arachidonic Acids; Bacterial Infections; Eicosanoids; Eicosapentaenoic Acid; Enteral Nutrition; Fish Oils; gamma-Linolenic Acid; Macrophages, Alveolar; Male; Phagocytosis; Plant Extracts; Prospective Studies; Prostaglandins E; Random Allocation; Rats; Rats, Sprague-Dawley; Respiratory Distress Syndrome; Staphylococcus aureus; Superoxides

Proinflammatory eicosanoids (cyclooxgenase and lipoxygenase metabolites of arachidonic acid) released by alveolar macrophages play an important role in endotoxin-induced acute lung injury. We investigated the effect of prefeeding rats for 21 days with enteral diets that provided the anti-inflammatory fatty acids, eicosapentaenoic acid and gamma-linolenic acid (derived from fish oil and borage oil, respectively), as compared with an n-6 fatty acid-enriched diet (corn oil) on the following: a) lung microvascular protein permeability, arterial blood pressure, and platelet and white blood cells in a model of endotoxin-induced acute lung injury; b) alveolar macrophage prostaglandin and leukotriene synthesis; and c) liver and alveolar macrophage phospholipid fatty acid composition.. Prospective, randomized, controlled, double-blind study.. Research laboratory at a university medical center.. Male Long-Evans rats, weighing 250 g.. Rats were randomized into four dietary treatment groups and fed nutritionally complete diets (300 kcal/kg/day), containing 55.2% of the total calories from fat with either 97% corn oil, 20% fish oil, 20% fish and 5% borage oil, or 20% fish and 20% borage oil for 21 days. On day 22, lung microvascular protein permeability, mean arterial pressure, and platelet and white blood cell counts were determined for 2 hrs after an intravenous injection of Salmonella enteritidis endotoxin (10 mg/kg). In a second group of prefed rats, the phospholipid fatty acid composition was determined in liver and alveolar macrophages. Alveolar macrophages were harvested by bronchoalveolar lavage and stimulated in vitro with a calcium ionophore (A23187), and the concentrations of leukotrienes B4 and B5, thromboxane A2, prostaglandin E2, and 6-keto-prostaglandin F1 alpha were measured in a third group of prefed rats.. Lung permeability was greatest with corn oil and was significantly attenuated with 20% fish oil and 20% fish and 5% borage oil, and this effect approached significance with 20% fish and 20% borage oil (p = .06). The early and late hypotensive effects of endotoxin were attenuated with 20% fish oil, 20% fish and 5% borage oil, and 20% fish and 20% borage oil, as compared with corn oil. Concentrations of leukotriene B4, prostaglandin E2, and thromboxane B2 released from A23187-stimulated alveolar macrophages were significantly lower with 20% fish oil and 20% fish and 20% borage oil, as compared with corn oil. The increase in lung microvascular protein permeability with 20% fish and 20% borage oil was not significantly different than the lung microvascular protein permeability that was found in animals receiving 20% fish oil (p = .20) and 20% fish and 5% borage oil (p = .31). Alveolar macrophage and liver phospholipid concentrations of arachidonic acid were lower, and the concentrations of eicosapentaenoic acid and docosahexaenic acid were higher, with 20% fish oil, and 5% borage oil, and 20% fish and 20% borage oil, as compared with corn oil. Dihomo-gamma-linolenic acid, the desaturated and elongated intermediate of gamma-linolenic acid, was increased with 20% fish and 20% borage oil, as compared with 20% fish oil and 20% fish and 5% borage oil.. The severity of pulmonary microvascular protein permeability and the degree of hypotension were reduced with fish or fish and borage oil diets, as compared with corn oil, in endotoxic rats. The reduced synthesis of the proinflammatory arachidonic acid-derived mediators, leukotriene B4, thromboxane B2, and prostaglandin E2 from stimulated alveolar macrophages was indicative of a decrease in arachidonic acid and an increase in eicosapentaenoic acid and docosahexaenoic acid in cell membrane phospholipids.

Topics: Animals; Capillary Permeability; Disease Models, Animal; Double-Blind Method; Drug Evaluation, Preclinical; Eicosapentaenoic Acid; Endotoxemia; gamma-Linolenic Acid; Lung; Macrophages, Alveolar; Male; Random Allocation; Rats; Rats, Inbred Strains; Respiratory Distress Syndrome