gamma-linolenic-acid and Sepsis

The usefulness of n-3 fatty acids, γ-linolenic acid and antioxidants in the critically ill is controversial. I propose that adverse outcome in the critically ill is due to excess production of proinflammatory cytokines and eicosanoids from polyunsaturated fatty acids (PUFAs), while generation of anti-inflammatory products of PUFAs may lead to a favorable outcome. Hence, I suggest that measurement of plasma levels of various cytokines, free radicals, and proinflammatory and anti-inflammatory products of PUFAs and correlating them to the clinical picture may pave the way to identify prognostic markers and develop newer therapeutic strategies to prevent and manage critical illness.

Topics: Antioxidants; Critical Illness; Fatty Acids, Omega-3; gamma-Linolenic Acid; Humans; Inflammation Mediators; Sepsis

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

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.. 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.. 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).. 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.. ClinicalTrials.gov: NCT00981877.

Topics: Aged; Aged, 80 and over; Antioxidants; Double-Blind Method; Eicosapentaenoic Acid; Enteral Nutrition; Female; gamma-Linolenic Acid; Humans; Male; Middle Aged; Prospective Studies; Sepsis; Time Factors; Treatment Outcome

The omega-3 (n-3) fatty acids docosahexaenoic acid and eicosapentaenoic acid, along with γ-linolenic acid and antioxidants, may modulate systemic inflammatory response and improve oxygenation and outcomes in patients with acute lung injury.. To determine if dietary supplementation of these substances to patients with acute lung injury would increase ventilator-free days to study day 28.. The OMEGA study, a randomized, double-blind, placebo-controlled, multicenter trial conducted from January 2, 2008, through February 21, 2009. Participants were 272 adults within 48 hours of developing acute lung injury requiring mechanical ventilation whose physicians intended to start enteral nutrition at 44 hospitals in the National Heart, Lung, and Blood Institute ARDS Clinical Trials Network. All participants had complete follow-up.. Twice-daily enteral supplementation of n-3 fatty acids, γ-linolenic acid, and antioxidants compared with an isocaloric control. Enteral nutrition, directed by a protocol, was delivered separately from the study supplement.. Ventilator-free days to study day 28.. The study was stopped early for futility after 143 and 129 patients were enrolled in the n-3 and control groups. Despite an 8-fold increase in plasma eicosapentaenoic acid levels, patients receiving the n-3 supplement had fewer ventilator-free days (14.0 vs 17.2; P = .02) (difference, -3.2 [95% CI, -5.8 to -0.7]) and intensive care unit-free days (14.0 vs 16.7; P = .04). Patients in the n-3 group also had fewer nonpulmonary organ failure-free days (12.3 vs 15.5; P = .02). Sixty-day hospital mortality was 26.6% in the n-3 group vs 16.3% in the control group (P = .054), and adjusted 60-day mortality was 25.1% and 17.6% in the n-3 and control groups, respectively (P = .11). Use of the n-3 supplement resulted in more days with diarrhea (29% vs 21%; P = .001).. Twice-daily enteral supplementation of n-3 fatty acids, γ-linolenic acid, and antioxidants did not improve the primary end point of ventilator-free days or other clinical outcomes in patients with acute lung injury and may be harmful.. clinicaltrials.gov Identifier: NCT00609180.

Topics: Acute Lung Injury; Adult; Aged; Antioxidants; Biomarkers; Dietary Supplements; Docosahexaenoic Acids; Double-Blind Method; Drug Therapy, Combination; Eicosapentaenoic Acid; Enteral Nutrition; Female; gamma-Linolenic Acid; Humans; Inflammation; Intensive Care Units; Male; Middle Aged; Pneumonia; Sepsis; Survival Analysis; Treatment Outcome; Ventilator Weaning

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

Topics: Antioxidants; Eicosapentaenoic Acid; Enteral Nutrition; Female; gamma-Linolenic Acid; Humans; Male; Sepsis

Topics: Antioxidants; Eicosapentaenoic Acid; Enteral Nutrition; Female; gamma-Linolenic Acid; Humans; Male; Sepsis

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

The effects of dietary treatment for 3 weeks with soybean oil, linseed- and safflower oil (high alpha-linolenic acid, ALA), or borage oil (high gamma-linolenic acid, GLA) on the liver fatty acid profile and lipid metabolism in fed rats, in normal fasted rats, and septic fasted rats, and on survival from sepsis, were studied. The results were the following: 1) Dietary ALA increased incorporation of alpha-linolenic (18:3w3), eicosapentaenoic (20:5w3), and docosapentaenoic (22:5w3) acids in neutral lipids and phospholipids, and docosahexaenoic (22:6w3), dihomo-gamma-linolenic (20:3w6), arachidonic (20:4w6), stearic (18:0), oleic (18:1w9), and linoleic (18:2w6) acids in phospholipids in the livers of fed, fasted, and septic fasted rats. Dietary GLA increased all w6 fatty acids except 18:2w6, and reduced all w3 fatty acids in neutral lipids and phospholipids. 2) Dietary ALA increased liver phospholipid content in fasted as well as in septic fasted rats and was more potent than GLA in lowering serum cholesterol and liver neutral lipids. 3) Dietary ALA counteracted sepsis-related changes in liver weight, platelet count, body temperature, prekallikrein, serum glucose, beta-hydroxybutyrate, and free fatty acids. 4) Dietary GLA reduced survival from sepsis. The results suggest a role for w3 fatty acids to balance w6 fatty acids in the septic state.

Topics: alpha-Linolenic Acid; Animals; Cholesterol; Disease Models, Animal; Fatty Acids; gamma-Linolenic Acid; Liver; Male; Phospholipids; Rats; Rats, Sprague-Dawley; Sepsis; Triglycerides