The purpose of this study is to determine whether fish oil (containing omega-3 fatty acids) given enterally is safe and effective in reducing lung and systemic inflammation seen in acute lung injury.
Acute lung injury (ALI) is common among critically ill patients and is associated with a high case fatality. Only one intervention has been shown to improve survival in a large clinical trial, and new therapies targeting the inflammatory response are needed. Nutrient interventions may provide benefit; specifically there is plausible biologic rationale for administering n-3 fatty acids (n-3 FAs) found in fish oil to patients with ALI, as n-3 FAs decrease formation of eicosanoid inflammatory mediators. However, although promising results have emerged from prior studies, fish oils have only been tested in ALI patients in a commercial enteral formula containing additional nutrients, and the control group received a high-fat enteral formula that may have been proinflammatory. Therefore, no conclusion can be drawn about the independent effect of fish oils. Furthermore, the inclusion of key pharmaconutrients in feeding formulas, instead of delivering them separately as pharmaceuticals, limits exposure to the agent, as intensive care unit (ICU) patients commonly receive less than 60% of prescribed caloric needs. Finally, specialized feeding formulas are very expensive, and it may be substantially cheaper to administer pharmaconutrients separately. We believe it is time to begin to approach nutrient trials in critically ill patients differently -- to move away from including them in feeding formulas and begin delivering them like pharmaceuticals. With appropriate scientific investigation and the use of non-nutrient placebos, this novel and innovative approach is a new paradigm of investigating nutrient delivery to critically ill patients. This study is a phase II randomized controlled trial to determine the effects of enteral eicosapentaenoic acid (EPA) and docosahexanoic acid (DHA), both n-3 FAs found in fish oil, versus placebo on the pulmonary and systemic environments, and on clinical outcomes, in patients with ALI. We will investigate the effect of fish oil administration on several biological markers of injury and inflammation in bronchoalveolar lavage fluid and serum, on pulmonary physiologic outcomes, and on clinical outcomes. Comparison(s): Mechanically ventilated patients with acute lung injury randomized to receive enteral fish oil versus compared to mechanically ventilated patients with acute lung injury randomized to receive placebo.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
90
Liquid fish oil 7.5cc enterally every 6 hours
St. Alphonsus Medical Center
Boise, Idaho, United States
Oregon Health Sciences University
Portland, Oregon, United States
University of Vermont/Fletcher Allen Health Care
Burlington, Vermont, United States
Harborview Medical Center
Seattle, Washington, United States
Change in Bronchoalveolar Lavage Fluid (BALF) Interleukin (IL)-8
30 patients in the fish oil group and 36 patients in the enteral saline group underwent the 2nd bronchoalveolar lavage (BAL). Participants did not undergo BALs after baseline if they were not intubated or had expired, but clinical followup data (e.g. mortality) were collected.
Time frame: Days 1 and 5
Change in BALF Leukotriene B4
30 patients in the fish oil group and 36 patients in the enteral saline group underwent the 2nd bronchoalveolar lavage (BAL). Participants did not undergo BALs after baseline if they were not intubated or had expired, but clinical followup data (e.g. mortality) were collected.
Time frame: Days 1 and 5
Change in BALF Interleukin-6
30 patients in the fish oil group and 36 patients in the enteral saline group underwent the 2nd bronchoalveolar lavage (BAL). Participants did not undergo BALs after baseline if they were not intubated or had expired, but clinical followup data (e.g. mortality) were collected.
Time frame: Days 1 and 5
Change in BALF Monocyte Chemotactic Protein-1
30 patients in the fish oil group and 36 patients in the enteral saline group underwent the 2nd bronchoalveolar lavage (BAL). Participants did not undergo BALs after baseline if they were not intubated or had expired, but clinical followup data (e.g. mortality) were collected.
Time frame: Days 1 and 5
Change in BALF Neutrophil Count
30 patients in the fish oil group and 36 patients in the enteral saline group underwent the 2nd bronchoalveolar lavage (BAL). Participants did not undergo BALs after baseline if they were not intubated or had expired, but clinical followup data (e.g. mortality) were collected.
Time frame: Days 1 and 5
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St. Michael's Hospital
Toronto, Ontario, Canada
Static Lung Compliance
30 patients in the fish oil group and 36 patients in the enteral saline group remained intubated on day 5 and had this outcome available.
Time frame: Day 5
Oxygenation
PaO2/FiO2 is the ratio of partial pressure of arterial oxygen to the fraction of inspired oxygen. 30 patients in the fish oil group and 36 patients in the enteral saline group remained intubated on day 5 and had this outcome available.
Time frame: Day 5
Change in Plasma Interleukin-8
30 patients in the fish oil group and 36 patients in the enteral saline group underwent 2nd blood draw on day 5. Participants did not undergo blood draws after baseline if they were discharged from the ICU or had expired, but clinical followup data (e.g. mortality) were collected.
Time frame: Days 1 and 5
Change in Plasma Leukotriene B4
30 patients in the fish oil group and 36 patients in the enteral saline group underwent 2nd blood draw on day 5. Participants did not undergo blood draws after baseline if they were discharged from the ICU or had expired, but clinical followup data (e.g. mortality) were collected.
Time frame: Days 1 and 5
Change in Plasma Interleukin-6
30 patients in the fish oil group and 36 patients in the enteral saline group underwent 2nd blood draw on day 5. Participants did not undergo blood draws after baseline if they were discharged from the ICU or had expired, but clinical followup data (e.g. mortality) were collected.
Time frame: Days 1 and 5
Change in Plasma Surfactant Protein D
30 patients in the fish oil group and 36 patients in the enteral saline group underwent 2nd blood draw on day 5. Participants did not undergo blood draws after baseline if they were discharged from the ICU or had expired, but clinical followup data (e.g. mortality) were collected.
Time frame: Days 1 and 5
Change in Plasma vonWillebrand Factor
30 patients in the fish oil group and 36 patients in the enteral saline group underwent 2nd blood draw on day 5. Participants did not undergo blood draws after baseline if they were discharged from the ICU or had expired, but clinical followup data (e.g. mortality) were collected.
Time frame: Days 1 and 5
Worst Multiple Organ Dysfunction Score (MODS) During First 28 Days After Study Enrollment
Full scale name is Multiple Organ Dysfunction Score (MODS), a scale measuring degree of organ dysfunction in critically ill patients. Minimum score is 0 and maximum score is 24, with 0 indicating no organ failure and 24 indicating severe failure of multiple organs.
Time frame: Throughout hospital stay
Ventilator-free Days During First 28 Days After Study Enrollment
Ventilator-free days is a common outcome measure in critical care research. A ventilator-free day is a day that a participant is alive and not receiving mechanical ventilation during the first 28 days after s/he enrolled in the study.
Time frame: 28 days
ICU-free Days During First 28 Days After Study Enrollment
ICU-free days is a common outcome measure in critical care research. An ICU-free day is a day that a participant is alive and not in the intensive care unit (ICU) during the first 28 days after s/he enrolled in the study.
Time frame: 28 days
Hospital Length of Stay
Time frame: At end of hospital admission
Hospital Mortality
Time frame: At end of hospitalization
60-day Mortality
Time frame: 60 days from day of enrollment into study
Change in Bronchoalveolar Lavage Fluid (BALF) Interleukin (IL)-8
15 patients in the fish oil group and 27 patients in the enteral saline group underwent the 3rd bronchoalveolar lavage (BAL). Participants did not undergo BALs after baseline if they were not intubated or had expired, but clinical followup data (e.g. mortality) were collected.
Time frame: Days 1 and 9
Change in BALF Leukotriene B4
15 patients in the fish oil group and 27 patients in the enteral saline group underwent the 3rd bronchoalveolar lavage (BAL). Participants did not undergo BALs after baseline if they were not intubated or had expired, but clinical followup data (e.g. mortality) were collected.
Time frame: Days 1 and 9
Change in BALF Interleukin-6
15 patients in the fish oil group and 27 patients in the enteral saline group underwent the 3rd bronchoalveolar lavage (BAL). Participants did not undergo BALs after baseline if they were not intubated or had expired, but clinical followup data (e.g. mortality) were collected.
Time frame: Days 1 and 9
Change in BALF Monocyte Chemotactic Protein-1
15 patients in the fish oil group and 27 patients in the enteral saline group underwent the 3rd bronchoalveolar lavage (BAL). Participants did not undergo BALs after baseline if they were not intubated or had expired, but clinical followup data (e.g. mortality) were collected.
Time frame: Days 1 and 9
Change in BALF Neutrophil Count
15 patients in the fish oil group and 27 patients in the enteral saline group underwent the 3rd bronchoalveolar lavage (BAL). Participants did not undergo BALs after baseline if they were not intubated or had expired, but clinical followup data (e.g. mortality) were collected.
Time frame: Days 1 and 9
Change in Plasma Interleukin-8
15 patients in the fish oil group and 27 patients in the enteral saline group underwent 3rd blood draw on day 9. Participants did not undergo blood draws after baseline if they were discharged from the ICU or had expired, but clinical followup data (e.g. mortality) were collected.
Time frame: Days 1 and 9
Change in Plasma Leukotriene B4
15 patients in the fish oil group and 27 patients in the enteral saline group underwent 3rd blood draw on day 9. Participants did not undergo blood draws after baseline if they were discharged from the ICU or had expired, but clinical followup data (e.g. mortality) were collected.
Time frame: Days 1 and 9
Change in Plasma Interleukin-6
15 patients in the fish oil group and 27 patients in the enteral saline group underwent 3rd blood draw on day 9. Participants did not undergo blood draws after baseline if they were discharged from the ICU or had expired, but clinical followup data (e.g. mortality) were collected.
Time frame: Days 1 and 9
Change in Plasma Surfactant Protein D
15 patients in the fish oil group and 27 patients in the enteral saline group underwent 3rd blood draw on day 9. Participants did not undergo blood draws after baseline if they were discharged from the ICU or had expired, but clinical followup data (e.g. mortality) were collected.
Time frame: Days 1 and 9
Change in Plasma vonWillebrand Factor
15 patients in the fish oil group and 27 patients in the enteral saline group underwent 3rd blood draw on day 9. Participants did not undergo blood draws after baseline if they were discharged from the ICU or had expired, but clinical followup data (e.g. mortality) were collected.
Time frame: Days 1 and 9