Comparison of Low and High Tidal Volumes in Acute Spinal Cord Injury

Study Overview
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Brief Summary
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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
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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.

Official Title
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Comparison of Mechanical Ventilation With Low and High Tidal Volumes in Acute Spinal Cord Injury: A Pilot Randomized Comparative Effectiveness Trial

Conditions
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Spinal Cord Injuries

Intervention / Treatment
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* Device: High tidal volume
* Device: Low tidal volume


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: High tidal volume<br>A high tidal volume (14-16 ml/kg pbw) with positive end-expiratory pressure will be applied during mechanical ventilation. | Device: High tidal volume<br>* A high tidal volume (14-16 ml/kg pbw) with positive end-expiratory pressure will be applied during mechanical ventilation.<br>|
| Active Comparator: Low tidal volume<br>A low tidal volume (8-10 ml/kg pbw) with positive end-expiratory pressure will be applied during mechanical ventilation. | Device: Low tidal volume<br>* A low tidal volume (8-10 ml/kg pbw) with positive end-expiratory pressure will be applied during mechanical ventilation.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. 21 Any new pneumonia episodes which meet the above criteria and developed 48 hrs after achieving target Vt will be recorded. | From the time of enrollment to time of discharge from hospital (about 6 weeks) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Feasibility as assessed by recruitment rate | Recruitment rate is the proportion of eligible people who provide consent. | At the time of consent (within 48 hours of hospital admission) | 
| Feasibility as assessed by adherence rate | Adherence rate is the proportion of participants in each group who receive the assigned intervention per protocol. | At the time of start of intervention (within 48 hours of hospital admission) | 
| Feasibility as assessed by retention rate | Retention rate is the proportion of participants in each group who complete all study procedures. | at the time of discharge from hospital (6 weeks) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Spinal cord injury, Mechanical ventilation, Pneumonia, Tidal volume