Airway Pressure Release Ventilation for Moderate-to-severe Acute Respiratory Distress Syndrome (EARL)

Saskatchewan Health Authority

Status

Completed

Conditions

Acute Respiratory Distress Syndrome

Treatments

Device: Airway pressure release ventilation

Device: Low tidal volume ventilation

Study type

Interventional

Funder types

Other

Identifiers

NCT04156438

REB-19-51

Details and patient eligibility

About

This study will examine the feasibility of a large clinical trial investigating the effectiveness of airway pressure release ventilation and low tidal volume ventilation for patients with moderate-to-severe acute respiratory distress syndrome.

Full description

Acute respiratory distress syndrome (ARDS) is a disease that has an incidence of 5% of hospitalized mechanically ventilated patients. ARDS is associated with high morbidity and mortality in critically ill patients, with mortality reported as high as 45% in severe ARDS. Patients who develop ARDS will require mechanical ventilation. Patients with ARDS are graded by the partial pressure of oxygen to fraction of inspired oxygen ratio (PaO2/FiO2) into three categories of severity: mild (PaO2/FiO2 201-300 mm Hg), moderate (PaO2/FiO2 101-200 mmHg), and severe (PaO2/FiO2 ≤ 100).

Volutrauma and barotrauma are thought to contribute to the development of ARDS and alter mortality. The damage that occurs to the lungs manifests itself as inflammation, which leads to poor gas exchange of oxygen and carbon dioxide. Several strategies of lung-protective mechanical ventilation have been investigated in ARDS, including the use of low tidal volume ventilation (LTVV) or ARDSNet strategy, high frequency oscillation ventilation (HFOV), and airway pressure release ventilation (APRV). Lung protective strategies may be best beneficial prior to the onset of the development of ARDS or early in the course of the disease. As a result of the ARDSNet trial, LTVV has been adopted as the usual standard of care of ventilation and safest mode of ventilation for patients with ARDS.

Recently, APRV has been proposed as a potential alternative to LTVV. APRV is a form of ventilation that keeps the lungs inflated through the majority of the breath cycle and allows patients to breathe spontaneously above this level of inflation. APRV allows for spontaneous respiration with increased airway pressure, potentially allowing for decreased sedation, shorter duration of mechanical ventilation, and decreased need for vasopressors. APRV has been associated with possible reduction in incidence of ARDS and in-hospital mortality in non-randomized observational studies. In patients with established ARDS, the use of APRV has also not been well studied, with most studies limited to small observational studies often with no comparison group. One randomized trial using APRV alone had less than 30% of patients having a diagnosis of ARDS and did not show any difference in any outcomes. Recently, Zhou and colleagues conducted a randomized trial comparing APRV to conventional ventilation in 138 mechanically ventilated patients with mild to severe ARDS and found that APRV may shorten the duration of mechanical ventilation and reduce intensive care unit (ICU) length of stay.

While some of these studies had shown promise of APRV compared to LTVV, there has not been acceptance of APRV into guidelines as first line ventilation, and recommendations of institutions such as the Canadian Agency for Drugs and Technology in Health (CADTH) recommends interpreting these results with caution. Consequently, there remains clinical equipoise on this issue. Some ICU clinicians will currently use APRV as a rescue mode of ventilation in ARDS in their clinical practice while others will continue with the use of LTVV. We would like to randomize patients to LTVV or APRV and examine the feasibility of conducting a large multicentre randomized controlled trial in Canada.

Enrollment

1 patient

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Fulfilling the diagnostic criteria of ARDS, according to the Berlin definition
Moderate to severe ARDS as defined as a PaO2: FiO2 ratio of ≤150 during invasive mechanical ventilation
Endotracheal intubation and mechanical ventilation for ARDS less than 48 hours

Exclusion criteria

Age less than 18 years
Pregnancy
Intracranial hypertension (suspected or confirmed)
Severe chronic obstructive pulmonary disease as defined by either:
1. FEV1/FVC less than 50% predicted, or
2. Chronic hypercarbia (PaCO2>45 mmHg), chronic hypoxemia (PaO2 < 55 mmHg) on room air, and/or elevated admission serum HCO3 >30 mmol/L
Presence of documented barotrauma, i.e. pneumothorax
Treatment with extracorporeal support (ECMO) at enrollment
Refractory shock
Advanced directives indicating preferences to not have advanced life support
Moribund patient, i.e. not expected to survive longer than 24 hours