Spinal Cord Injuries
Conditions
Keywords
Spinal cord injury, Mechanical ventilation, Pneumonia, Tidal volume
Brief summary
Objective: This study's primary objective is to evaluate the efficacy and feasibility of mechanical ventilation with high vs. low tidal volume (Vt) in people with acute spinal cord injury (SCI). Secondary objectives include a comparison of inflammatory markers between these groups. Study Design: Randomized comparative effectiveness trial Methods: Study population: Adults with acute traumatic SCI on mechanical ventilation (MV). Subjects will be randomized to receive either a lower Vt of 8-10 cc/kg predicted body weight (pbw) or a high Vt of 14-16 ml/kg pbw. Risks and potential Benefits: Risks of study interventions are similar to usual care as proposed tidal volume settings are within the current usual care range. However, people assigned to the lower tidal volume group may have a lower risk of pneumonia and respiratory complications.
Detailed description
Background: Respiratory complications associated with mechanical ventilation (MV) are the leading cause of morbidity and mortality following acute spinal cord injury (SCI). Emerging evidence suggests pneumonia is also associated with reduced neurologic recovery. Therefore, pneumonia prevention is of primary importance to improve outcomes. In the non-SCI population, MV with lower tidal volume (Vt) has been shown to reduce inflammation and rates of pneumonia. High Vt MV results in disruption of pulmonary endothelium and release of inflammatory mediators, which play a role in the development of pulmonary complications. In contrast, guidelines for SCI practitioners recommend MV with higher Vt without strong evidence. Objective: The primary objective of this study is to evaluate the feasibility of conducting a randomized control trial comparing MV with high vs. low Vt. Secondary objectives include a comparison of clinical outcomes and inflammatory mediators between these groups. Methods: Study population: Adults with acute traumatic SCI admitted to an acute inpatient rehabilitation facility on MV. Subjects will be randomized to receive either a lower Vt of 8-10 cc/kg predicted body weight (pbw) or a high Vt of 14-16 ml/kg pbw. Study participants will be randomly assigned to high tidal volume (14-16 ml/kg pbw) or low tidal volume of 8 to 10 ml/kg pbw within 48 hrs of admission, stratified based on vital capacity at admission to ensure equal allocation of those with most severe respiratory impairment and unlikely to wean from the vent. Importance of knowledge gained from the study: Investigators believe the completion of this study will add to the fund of knowledge of respiratory management of people with SCI, especially at the early stages of the injury, including reducing respiratory complications in people with SCI who are at very high risk of severe respiratory complications which is the main cause of morbidity and mortality in this population.
Interventions
DEVICEHigh tidal volume
A high tidal volume (14-16 ml/kg pbw) with positive end-expiratory pressure will be applied during mechanical ventilation.
DEVICELow tidal volume
A low tidal volume (8-10 ml/kg pbw) with positive end-expiratory pressure will be applied during mechanical ventilation.
Sponsors
TIRR Memorial Hermann
Craig Hospital
National Center for Advancing Translational Sciences (NCATS)
The Craig H. Neilsen Foundation
The University of Texas Health Science Center, Houston
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Masking description
Participants, principal investigator, outcome assessors, and statistician will be blinded to tidal volume assignment.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adult patients ≥ 18 years (Lung volumes and ventilator settings are different for ages \<18 years). * Acute SCI of duration ≤ four months * Mechanical ventilation subjects: traumatic or non-traumatic cervical SCI with neurological level C1-C5 admitted to our acute inpatient rehabilitation facility (AIR) on mechanical ventilation
Exclusion criteria
* Severe dysphagia due to concomitant brain stem injury, which increases the risk of pneumonia * Severe brain injury resulting in dysphagia and inability to follow instructions to perform vital capacity measurements * ARDS or severe lung disease (required supplemental oxygen or ventilator prior to SCI) at the time of admission (these conditions will not allow patients to randomize because target vt may below) * Prolonged antibiotics for \> 3 weeks at the time of admission due to infection (e.g., osteomyelitis, epidural abscess, etc.), * Presence of diaphragmatic pacemaker.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Episodes of Pneumonia | From the time of enrollment to time of discharge from hospital (about 6 weeks) | The primary outcome is pneumonia episodes with evidence of new or progressive and persistent infiltrate on chest radiograph plus 2 of the following abnormal white blood cell count, presence of fever or hyperthermia, purulent sputum, and deterioration in gas exchange. Any new pneumonia episodes which meet the above criteria and developed 48 hours after achieving target tidal volume will be recorded. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Feasibility as Assessed by Recruitment Rate | At the time of consent (within 48 hours of hospital admission) | Recruitment rate is the proportion of eligible people who provide consent. |
| Feasibility as Assessed by Adherence Rate | At the time of start of intervention (within 48 hours of hospital admission) | Adherence rate is the proportion of participants in each group who receive the assigned intervention per protocol. |
| Feasibility as Assessed by Retention Rate | at the time of discharge from hospital (about 6 weeks after admission) | Retention rate is the number of participants in each group who complete all study procedures. |
| Feasibility as Assessed by Number of Participants With Missing Data | From the time of enrollment to time of discharge from hospital (about 6 weeks) | — |
Other
| Measure | Time frame | Description |
|---|---|---|
| Number of Respiratory Complications | From the time of enrollment to the time of discharge from the hospital (about 6 weeks) | The following ventilator-associated events will be reported: transfer to acute care hospital due to respiratory complications, weaning failure, new pneumothorax, Acute respiratory distress syndrome (ARDS), pleural effusion, pulmonary embolism, atelectasis, and pulmonary edema. |
Countries
United States
Participant flow
Pre-assignment details
A total of 62 participants were screened for eligibility. Of those, 31 met the inclusion criteria and signed informed consent. One participant was transferred before randomization and did not continue in the study. A total of 31 participants were enrolled, and 30 were randomized.
Participants by arm
| Arm | Count |
|---|---|
| Low Tidal Volume A low tidal volume (8-10 ml/kg pbw) with positive end-expiratory pressure will be applied during mechanical ventilation.
Low tidal volume: A low tidal volume (8-10 ml/kg pbw) with positive end-expiratory pressure will be applied during mechanical ventilation. | 15 |
| High Tidal Volume A high tidal volume (14-16 ml/kg pbw) with positive end-expiratory pressure will be applied during mechanical ventilation.
High tidal volume: A high tidal volume (14-16 ml/kg pbw) with positive end-expiratory pressure will be applied during mechanical ventilation. | 15 |
| Total | 30 |
Baseline characteristics
| Characteristic | Low Tidal Volume | High Tidal Volume | Total |
|---|---|---|---|
| Age, Continuous | 54 years STANDARD_DEVIATION 13 | 44 years STANDARD_DEVIATION 17 | 49 years STANDARD_DEVIATION 15.13 |
| Asia Impairment Scale Classification A | 9 Participants | 11 Participants | 20 Participants |
| Asia Impairment Scale Classification B | 5 Participants | 2 Participants | 7 Participants |
| Asia Impairment Scale Classification C | 1 Participants | 2 Participants | 3 Participants |
| Asia Impairment Scale Classification D | 0 Participants | 0 Participants | 0 Participants |
| Cause of injury Fall | 4 Participants | 3 Participants | 7 Participants |
| Cause of injury Medical/Surgical Complications | 1 Participants | 0 Participants | 1 Participants |
| Cause of injury Other traumatic Injuries | 0 Participants | 1 Participants | 1 Participants |
| Cause of injury Sports | 1 Participants | 3 Participants | 4 Participants |
| Cause of injury Vehicular | 8 Participants | 7 Participants | 15 Participants |
| Cause of injury Violence | 1 Participants | 1 Participants | 2 Participants |
| Neurological Level of Spinal Cord Injury (SCI) C1 to C3 | 7 Participants | 9 Participants | 16 Participants |
| Neurological Level of Spinal Cord Injury (SCI) C4 to C5 | 8 Participants | 6 Participants | 14 Participants |
| Number of participants with a history of concomitant mild traumatic brain injury or stroke | 5 Participants | 2 Participants | 7 Participants |
| Number of participants with a history of lung or pulmonary disorders prior to Spinal Cord Injury | 0 Participants | 1 Participants | 1 Participants |
| Number of Participants with a smoking history | 5 Participants | 3 Participants | 8 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 1 Participants | 4 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 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 | 1 Participants | 2 Participants | 3 Participants |
| Race (NIH/OMB) White | 10 Participants | 10 Participants | 20 Participants |
| Region of Enrollment United States | 15 participants | 15 participants | 30 participants |
| Sex: Female, Male Female | 2 Participants | 4 Participants | 6 Participants |
| Sex: Female, Male Male | 13 Participants | 11 Participants | 24 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 15 | 1 / 15 |
| other Total, other adverse events | 12 / 15 | 12 / 15 |
| serious Total, serious adverse events | 0 / 15 | 1 / 15 |
Outcome results
Primary
Number of Episodes of Pneumonia
The primary outcome is pneumonia episodes with evidence of new or progressive and persistent infiltrate on chest radiograph plus 2 of the following abnormal white blood cell count, presence of fever or hyperthermia, purulent sputum, and deterioration in gas exchange. Any new pneumonia episodes which meet the above criteria and developed 48 hours after achieving target tidal volume will be recorded.
Time frame: From the time of enrollment to time of discharge from hospital (about 6 weeks)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| High Tidal Volume | Number of Episodes of Pneumonia | .13 episodes of pneumonia | Standard Deviation 0.35 |
| Low Tidal Volume | Number of Episodes of Pneumonia | .4 episodes of pneumonia | Standard Deviation 0.5 |
Secondary
Feasibility as Assessed by Adherence Rate
Adherence rate is the proportion of participants in each group who receive the assigned intervention per protocol.
Time frame: At the time of start of intervention (within 48 hours of hospital admission)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| High Tidal Volume | Feasibility as Assessed by Adherence Rate | 11 Participants |
| Low Tidal Volume | Feasibility as Assessed by Adherence Rate | 13 Participants |
Secondary
Feasibility as Assessed by Number of Participants With Missing Data
Time frame: From the time of enrollment to time of discharge from hospital (about 6 weeks)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| High Tidal Volume | Feasibility as Assessed by Number of Participants With Missing Data | 0 Participants |
| Low Tidal Volume | Feasibility as Assessed by Number of Participants With Missing Data | 0 Participants |
Secondary
Feasibility as Assessed by Recruitment Rate
Recruitment rate is the proportion of eligible people who provide consent.
Time frame: At the time of consent (within 48 hours of hospital admission)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| High Tidal Volume | Feasibility as Assessed by Recruitment Rate | 31 Participants |
Secondary
Feasibility as Assessed by Retention Rate
Retention rate is the number of participants in each group who complete all study procedures.
Time frame: at the time of discharge from hospital (about 6 weeks after admission)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| High Tidal Volume | Feasibility as Assessed by Retention Rate | 15 Participants |
| Low Tidal Volume | Feasibility as Assessed by Retention Rate | 15 Participants |
Other Pre-specified
Number of Respiratory Complications
The following ventilator-associated events will be reported: transfer to acute care hospital due to respiratory complications, weaning failure, new pneumothorax, Acute respiratory distress syndrome (ARDS), pleural effusion, pulmonary embolism, atelectasis, and pulmonary edema.
Time frame: From the time of enrollment to the time of discharge from the hospital (about 6 weeks)