Hyperglycemia, Respiratory Distress Syndrome, Adult, Sepsis
Conditions
Keywords
Acute Respiratory Distress Syndrome, Acute Lung Injury
Brief summary
Acute Lung Injury/Acute Respiratory Distress Syndrome (ALI/ARDS) is a severe lung condition that causes respiratory failure. Symptoms usually develop within 24 to 48 hours of an original injury or illness, and people with ALI/ARDS typically require care in the intensive care unit (ICU). Little is known about how to prevent the onset of ALI/ARDS. The purpose of this study is to examine if early infusions of insulin, known as intensive insulin therapy (IIT), can help prevent ALI/ARDS in hospitalized patients with high levels of blood sugars and severe infections.
Detailed description
ALI/ARDS is a life-threatening condition that involves inflammation of the lungs and fluid accumulation in the air sacs, leading to low blood oxygen levels and respiratory failure. Common causes include pneumonia, lung trauma, and sepsis, a condition that can lead to widespread inflammation and blood clotting in response to an infection. Recent studies have shown that insulin, which is regularly used to control blood sugar levels, may prevent or lessen the risk of lung tissue inflammation and/or lung injury related to sepsis. Research has shown that critically ill ICU patients often benefit from receiving insulin to target 80-110 mg/dl , but it is not known if insulin to target these levels can prevent the onset of ALI/ARDS. Therapies to prevent ALI/ARDS should occur early, preferably even prior to ICU admission, because at least 38% of people with ALI/ARDS are diagnosed with the condition once they reach the ICU. The purpose of this study is to determine whether insulin to target 80-110 mg/dl administered to critically ill patients in the emergency department (ED) is more beneficial at preventing ALI/ARDS than insulin to target 150-180 mg/dl after ICU admission. This study will enroll people who are hospitalized with high blood sugar levels and severe sepsis. Participants will be randomly assigned to receive IIT within 6-12 hours of ED presentation to target 80-110 mg/dl or target 150-180 mg/dl for 48 hours after admission to the ICU followed by usual care. Prior to ICU admission and 1, 3, and 7 days after ICU admission, blood will be collected and analyzed for markers of inflammation and lung injury. Blood samples will be stored for future research studies. While participants are in the hospital, their medical records will be reviewed to gather information on medical and family history, demographics, vital signs, laboratory test results, x-ray findings, and lung function. Study researchers will also monitor participants for the development of severe lung failure or other organ failures.
Interventions
DRUGInsulin
Participants will receive intravenous insulin to target tight glycemic control (80 to 110 mg/dL) for up to 48 hours after ICU admission.
Sponsors
National Heart, Lung, and Blood Institute (NHLBI)
Albert Einstein College of Medicine
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosed with severe sepsis, which is defined as sepsis AND one or more signs of organ dysfunction or hypotension * Hyperglycemia (i.e., glucose level greater than 130 mg/dL on one or more tests)
Exclusion criteria
* Diabetic ketoacidosis * Severe chronic liver disease with Child-Pugh score greater than 10 (Class C) * Documented episodes of blood or plasma glucose less than 60 mg/dL within 24 hours of study entry * Lack of any available IV access for insulin infusion * Pregnant * Known advanced directives against intubation or aggressive ICU care * Inability to be enrolled into the study in the 12 hours following admission to the ED
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Plasma Levels of Free Fatty Acids, Tumor Necrosis Factor-α, Interleukin-6, and Von Willebrand Factor Antigen | Measured at Day 1, 3 and 7 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Murray Lung Injury Score | Measured at Day 3 | Murray Lung Injury Score is a continuous score that quantifies the severity of lung injury and consist of components related to severity of hypoxia, pulmonary compliance, peep, and radiologic abnormalities. The scores range between 0 - 4. The higher the score, the greater the degree and severity of lung injury. The scale runs from 0-4, with 0 being the minimum and 4 the maximum score. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Early Insulin Group Participants will receive IIT within 6-12 hours after presenting to ED.
Insulin : Participants will receive intravenous insulin to target tight glycemic control (80 to 110 mg/dL) either in the ED or 48 hours after admission to the ICU. | 7 |
| Control Group Participants will receive insulin to target 150-180 mg/dl for 48 hours after ICU admission followed by usual clinical care.
Insulin : Participants will receive intravenous insulin to target tight glycemic control (80 to 110 mg/dL) either in the ED or 48 hours after admission to the ICU. | 11 |
| Total | 18 |
Baseline characteristics
| Characteristic | Control Group | Early Insulin Group | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 7 Participants | 5 Participants | 12 Participants |
| Age, Categorical Between 18 and 65 years | 4 Participants | 2 Participants | 6 Participants |
| Age, Continuous | 70 years STANDARD_DEVIATION 18 | 74 years STANDARD_DEVIATION 21 | 72 years STANDARD_DEVIATION 19 |
| Region of Enrollment United States | 11 participants | 7 participants | 18 participants |
| Sex: Female, Male Female | 5 Participants | 7 Participants | 12 Participants |
| Sex: Female, Male Male | 6 Participants | 0 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 7 | 0 / 11 |
| other Total, other adverse events | 2 / 7 | 0 / 11 |
| serious Total, serious adverse events | 0 / 7 | 0 / 11 |
Outcome results
Primary
Plasma Levels of Free Fatty Acids, Tumor Necrosis Factor-α, Interleukin-6, and Von Willebrand Factor Antigen
Time frame: Measured at Day 1, 3 and 7
Population: Although blood samples were collected, there were no bioassays perfomed and therefore no data were collected from any study participants.
Secondary
Murray Lung Injury Score
Murray Lung Injury Score is a continuous score that quantifies the severity of lung injury and consist of components related to severity of hypoxia, pulmonary compliance, peep, and radiologic abnormalities. The scores range between 0 - 4. The higher the score, the greater the degree and severity of lung injury. The scale runs from 0-4, with 0 being the minimum and 4 the maximum score.
Time frame: Measured at Day 3
Population: Change in Murray Lung Injury score from Day 3 to Day 0 (baseline)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Early Insulin Group | Murray Lung Injury Score | 0.333 units on a scale | Standard Deviation 0.81 |
| Control Group | Murray Lung Injury Score | 0.323 units on a scale | Standard Deviation 1.03 |