Acute Respiratory Distress Syndrome
Conditions
Keywords
ARDS, Shock Lung, Acute Chest Syndrome, Respiratory Distress Syndrome, Adult, Respiratory insufficiency, Trauma
Brief summary
A randomized, concurrent controlled trial to assess if adding sigh breaths to usual invasive mechanical ventilation of victims of trauma who are at risk of developing ARDS will decrease the number of days they require invasive mechanical ventilation.
Detailed description
Patients in intensive care units (ICUs) as a result of injuries resulting from penetrating or non-penetrating trauma who are intubated and receiving invasive mechanical ventilation will be randomized to either usual care or usual care with the addition of sigh breaths given once every 6 minutes. Patients will be randomized to one of the two study arms as soon as possible, but not longer than 24 hours after initiation of invasive mechanical ventilation. Patients will be followed for 28 days to assess ventilator-free days (VFDs), mortality, ICU-free days, and the occurrence of complications.
Interventions
OTHERSigh breaths
Sigh breaths delivered once every 6 minutes, as part of usual invasive mechanical ventilation.
Sponsors
United States Department of Defense
University of Colorado, Denver
University of Minnesota
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 89 Years
Healthy volunteers
No
Inclusion criteria
Patients in an intensive care unit (ICU) as a result of injuries resulting from penetrating or non-penetrating trauma who are intubated and receiving invasive mechanical ventilation who also have one or more of the following: 1. Traumatic brain injury 2. \> 1 long bone fractures 3. Shock on arrival in the Emergency Department (systolic BP \< 90 mmHg) 4. Lung contusion 5. Receipt of \> 6 units of blood
Exclusion criteria
1. Inability to obtain consent from the patient or his/her legally authorized representative (LAR) 2. Unwillingness of the treating physician to use sigh ventilation as all treating physicians must have equipoise with respect to the intervention 3. Age limitations per Institutional Review Board regulations 4. Undergoing invasive mechanical ventilation for \> 24 hours, excluding any time during which the patient was being ventilated in the operating room, CT or IR, as this could represent too long a delay in instituting the intervention for it to have a chance of being effective 5. Presence of malignancy or other irreversible disease or condition for which the six month mortality is estimated to exceed 50% (e.g., chronic liver disease with a Child-Pugh Score of 10-15, malignancy refractory to treatment) as this could affect the clinical course and cloud interpretation of the endpoints 6. Women who are pregnant (negative pregnancy tests required on women of child-bearing age) per Human Subjects regulations 7. Prisoners, per Human Subjects regulations 8. Neurological condition that could impair spontaneous ventilation (e.g., C5 or higher spinal cord injury as this could affect the clinical course and cloud interpretation of the ventilator-free day endpoint 9. Lack of availability of Dräger Evita Infinity V500 ventilator as this is the only ventilator capable of delivering sigh breaths as described in the protocol 10. Burns \> 40% of body surface area as this could affect the clinical course and cloud interpretation of the endpoints 11. Treating physicians being unwilling to use low VT ventilation strategy when ARDS is diagnosed as low VT ventilation is now considered standard of care for patients with ARDS. 12. Moribund, not expected to survive 24 hours as this could affect the clinical course and cloud interpretation of the endpoints13. Treating physician's decision to use airway pressure release ventilation (APRV). 13. Patient not expected to require mechanical ventilation \> 24 hours (e.g., intubated for alcohol intoxication rather than pulmonary problem).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Ventilator-free Days (VFDs) | 28 days | Ventilator-free days (VFDs), defined as the number of days of unassisted breathing to day 28 without having to re-institute invasive ventilation. Patients who died before day 28 were assigned 0 VFDs as were those transferred to a long-term care facility while ventilated. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| All-cause Mortality | 28 days | All-cause 28 day mortality |
| ICU-free Days | 28 days | Number of ICU-free days to day 28 after enrollment |
| Number of Participants With Complications of Treatment | 28 days | Specifically the number of participants experiencing pneumothorax, ventilator-associated pneumonia, hypotension requiring pressors, or pneumatoceles. |
| Discharge Status | 28 days | Percentage of patients discharged to extended care facilities, on mechanical ventilation, or to in-patient or home hospice |
| Number of Participants Requiring Oxygen Therapy at Discharge | 28 days | Number of Participants newly requiring continuous oxygen therapy at discharge. |
Countries
United States
Participant flow
Recruitment details
Patients were recruited in 15 trauma centers in the United States from April, 2016, to September, 2022.
Pre-assignment details
All analyses were based on the intention-to-treat principle. Participants were included in the primary analysis if primary endpoint data was available (ventilator-free days (VFDs), defined as the number of days of unassisted breathing to day 28 without having to re-institute invasive ventilation).
Participants by arm
| Arm | Count |
|---|---|
| Sigh Breaths Sigh breaths consisting of a Tidal volume (VT) that produces a plateau pressure (Pplat) of 35 cmH2O (or 40 cmH2O in patients with BMIs \> 35 or in patients with moderate or severe abdominal distension from ascites, blood and/or ileum, or prone patients). The sigh breaths will be delivered once every 6 minutes, as part of usual invasive mechanical ventilation.
Sigh breaths: Sigh breaths delivered once every 6 minutes, as part of usual invasive mechanical ventilation. | 261 |
| Usual Care Usual care, meaning that the treating physician will be free to treat the patient in any way he or she sees fit, including utilizing invasive mechanical ventilation as they wish. | 263 |
| Total | 524 |
Baseline characteristics
| Characteristic | Total | Usual Care | Sigh Breaths |
|---|---|---|---|
| Age, Continuous Age | 43.9 years STANDARD_DEVIATION 19.2 | 44.2 years STANDARD_DEVIATION 19.2 | 43.7 years STANDARD_DEVIATION 19.1 |
| Arterial blood gas FIO2 | 47.6 mmHg STANDARD_DEVIATION 18.1 | 47.1 mmHg STANDARD_DEVIATION 17.2 | 48.2 mmHg STANDARD_DEVIATION 18.9 |
| Arterial blood gas PaCO2 | 38.9 mmHg STANDARD_DEVIATION 7.6 | 38.6 mmHg STANDARD_DEVIATION 7.8 | 39.1 mmHg STANDARD_DEVIATION 7.4 |
| Arterial blood gas PaO2 | 154.9 mmHg STANDARD_DEVIATION 82 | 152.5 mmHg STANDARD_DEVIATION 79.9 | 157.4 mmHg STANDARD_DEVIATION 84.2 |
| Arterial blood gas pH | 7.36 pH STANDARD_DEVIATION 0.08 | 7.37 pH STANDARD_DEVIATION 0.08 | 7.36 pH STANDARD_DEVIATION 0.08 |
| BMI | 28.5 kg/m^2 STANDARD_DEVIATION 6.5 | 28.4 kg/m^2 STANDARD_DEVIATION 6.5 | 28.7 kg/m^2 STANDARD_DEVIATION 6.4 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 85 Participants | 42 Participants | 43 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 439 Participants | 221 Participants | 218 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Hours on ventilator prior to randomization | 17.0 hours STANDARD_DEVIATION 5.8 | 17.0 hours STANDARD_DEVIATION 5.9 | 17.1 hours STANDARD_DEVIATION 5.8 |
| Injury Severity Score | 29.4 units on a scale STANDARD_DEVIATION 12.3 | 29.9 units on a scale STANDARD_DEVIATION 11.7 | 28.8 units on a scale STANDARD_DEVIATION 12.9 |
| P/F ratio | 349.2 Ratio STANDARD_DEVIATION 193.8 | 349.8 Ratio STANDARD_DEVIATION 214 | 347.6 Ratio STANDARD_DEVIATION 172 |
| Race (NIH/OMB) American Indian or Alaska Native | 2 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Asian | 5 Participants | 4 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 107 Participants | 52 Participants | 55 Participants |
| Race (NIH/OMB) More than one race | 3 Participants | 3 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 405 Participants | 203 Participants | 202 Participants |
| Region of Enrollment United States | 524 participants | 263 participants | 261 participants |
| Sex: Female, Male Female | 130 Participants | 66 Participants | 64 Participants |
| Sex: Female, Male Male | 394 Participants | 197 Participants | 197 Participants |
| Smoking status Current/Past | 237 Participants | 103 Participants | 134 Participants |
| Smoking status Never | 145 Participants | 80 Participants | 65 Participants |
| Smoking status Unknown/Missing | 142 Participants | 80 Participants | 62 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 30 / 259 | 46 / 261 |
| other Total, other adverse events | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 103 / 259 | 114 / 261 |
Outcome results
Primary
Ventilator-free Days (VFDs)
Ventilator-free days (VFDs), defined as the number of days of unassisted breathing to day 28 without having to re-institute invasive ventilation. Patients who died before day 28 were assigned 0 VFDs as were those transferred to a long-term care facility while ventilated.
Time frame: 28 days
Population: Analysis based on participants with available follow-up data
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sigh Breaths | Ventilator-free Days (VFDs) | 18.4 days |
| Usual Care | Ventilator-free Days (VFDs) | 16.1 days |
Secondary
All-cause Mortality
All-cause 28 day mortality
Time frame: 28 days
Population: Analysis population based on those with follow-up data available
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Sigh Breaths | All-cause Mortality | 30 Participants |
| Usual Care | All-cause Mortality | 46 Participants |
Secondary
Discharge Status
Percentage of patients discharged to extended care facilities, on mechanical ventilation, or to in-patient or home hospice
Time frame: 28 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Sigh Breaths | Discharge Status | 6 Participants |
| Usual Care | Discharge Status | 5 Participants |
Secondary
ICU-free Days
Number of ICU-free days to day 28 after enrollment
Time frame: 28 days
Population: Analysis based on participants with available follow-up data
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sigh Breaths | ICU-free Days | 13.7 days |
| Usual Care | ICU-free Days | 11.9 days |
Secondary
Number of Participants Requiring Oxygen Therapy at Discharge
Number of Participants newly requiring continuous oxygen therapy at discharge.
Time frame: 28 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Sigh Breaths | Number of Participants Requiring Oxygen Therapy at Discharge | 20 Participants |
| Usual Care | Number of Participants Requiring Oxygen Therapy at Discharge | 12 Participants |
Secondary
Number of Participants With Complications of Treatment
Specifically the number of participants experiencing pneumothorax, ventilator-associated pneumonia, hypotension requiring pressors, or pneumatoceles.
Time frame: 28 days
Population: Analysis based on participants with available follow-up data
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Sigh Breaths | Number of Participants With Complications of Treatment | Pneumothorax | 18 Participants |
| Sigh Breaths | Number of Participants With Complications of Treatment | Hypotension requiring pressors | 127 Participants |
| Sigh Breaths | Number of Participants With Complications of Treatment | Ventilator-associated pneumonia | 57 Participants |
| Sigh Breaths | Number of Participants With Complications of Treatment | Pneumatocele | 1 Participants |
| Usual Care | Number of Participants With Complications of Treatment | Pneumatocele | 2 Participants |
| Usual Care | Number of Participants With Complications of Treatment | Pneumothorax | 20 Participants |
| Usual Care | Number of Participants With Complications of Treatment | Ventilator-associated pneumonia | 69 Participants |
| Usual Care | Number of Participants With Complications of Treatment | Hypotension requiring pressors | 120 Participants |