Early Use of Airway Pressure Release Ventilation (APRV) in ARDS

Study Overview
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Brief Summary
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Airway pressure release ventilation (APRV) is a time-cycled, pressure controlled, intermittent mandatory ventilation mode with extreme inverse I:E ratios. Currently it is considered as a non-conventional ventilatory mode. The investigators aim to compare APRV with conventional mechanical ventilation (MV) in patients with acute respiratory distress syndrome (ARDS).

Detailed Description
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Despite the advances in technology and ventilatory modes, mortality of ARDS is still around 40%. Besides prone positioning, the best approach of management is low tidal volume ventilation (LTV). This 'protective ventilation' strategy is not aways effective to improve oxygenation and is associated with an increased requirement of sedation and neuromuscular blocking agents, which increase length of stay and morbidity. APRV is a ventilatory mode based on relatively high and sustained continuous positive pressure, combined with a short phase of release to allow carbon dioxide removal. It also allows unrestricted spontaneous breathing throughout respiration, independent of the ventilator cycle. Providing sustained inflation while limiting duration and frequency of release phase permits limiting volume loss, resulting in progressive and improved alveolar recruitment, an increased alveolar surface area available for gas exchange and improved ventilation-perfusion matching. In this multi-center, prospective, randomized, controlled, open trial, the investigators aim to compare the effects and safety of the early application of time-controlled adaptive method of APRV and conventional ventilation with LTV strategy in patients with severe to moderate ARDS.

Official Title
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Early Use of Airway Pressure Release Ventilation (APRV) in Patients With Acute Respiratory Distress Syndrome

Conditions
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Acute Respiratory Distress Syndrome

Intervention / Treatment
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* Device: APRV. General Electric Healthcare Engstrom ventilator system
* Device: Conventional. General Electric Healthcare Engstrom ventilator system


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Acute respiratory distress syndrome, according to the Berlin definition of ARDS, with adjusted pO2/FiO2 for altitude <300, and less than 48 h of endotracheal mechanical ventilation Exclusion Criteria: Pregnancy Less than 18 years-old Expected duration of mechanical ventilation less than 48 h Preexisting conditions with an expected 3-month mortality exceeding 50% Concurrent chemotherapy Confirmed intracranial hypertension Catastrophic cranial trauma or neuromuscular disorders that are known to prolong mechanical ventilation Pneumothorax at enrollment (resolved or not) Do-not-resuscitate order

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Conventional ventilation<br>Protective lung conventional strategy with volume-controlled ventilation (VCV) or pressure-controlled ventilation (PCV) mode, with low tidal volume and adequate positive end expiratory pressure (PEEP) level. | Device: Conventional. General Electric Healthcare Engstrom ventilator system<br>* Lung protective ventilation consist of delivery of low tidal volumes (4-6 ml/kg PBW), high PEEP enough to avoid de-recruitment, titrated according to ARDSNet PEEP/fraction of inspired oxygen (FiO2) table, while avoiding excessive transpulmonary pressure.<br>|
| Experimental: Time-controlled adaptive APRV<br>Airway Pressure Release Ventilation with Time-controlled adaptive ventilation method. Allowing for spontaneous breathing. | Device: APRV. General Electric Healthcare Engstrom ventilator system<br>* APRV consist of an extended time at plateau pressure (a continuous positive airway pressure phase) comprising about 90% of the respiratory cycle, while providing very brief releases to enhance carbon dioxide removal. Time-controlled adaptive method requires interpretation of the expiratory flow curve to assess changes in lung elastance and, therefore, set the Time low to optimize carbon dioxide removal, but not at the expense of alveolar derecruitment and instability.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mechanical ventilation free days |  | 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| All causes mortality |  | 28 days | 
| ICU length of stay |  | 28 days | 
| Hospital length of stay |  | 60 days | 
| Mean airway pressure, peak airway pressure, maximum P high | Measured in cmH20 | 7 days | 
| Average expiratory time | Measured in seconds | 7 days | 
| Minute ventilation |  | 7 days | 
| oxygen partial pressure (pO2) |  | 7 days | 
| pCO2 (carbon dioxide partial pressure) |  | 7 days | 
| Mean arterial pressure |  | 7 days | 
| Maximum dosage of vasopressors requirement |  | 7 days | 
| Richmond Sedation-Agitation Scale | Range from -5 (unarousable) to +4 (combative) | 7 days | 
| Average dose of propofol use |  | 7 days | 
| Rate of neuromuscular blocking agents utilization |  | 7 days | 
| Prone position rate |  | 7 days | 
| Average of prone position sessions |  | 7 days | 
| Rate of recruitment maneuvers |  | 7 days | 
| Tracheostomy rate |  | 28 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Mechanical Ventilation, Acute Respiratory Distress Syndrome, Acute Lung Injury, APRV