Physiologic Effects of Continuous Positive Airway Pressure and High Flow Nasal Oxygenation in Patients with Acute Respiratory Distress Syndrome.

The acute respiratory distress syndrome (ARDS) is defined as an acute hypoxemic respiratory failure with non-cardiogenic pulmonary opacities. This condition has been recently extended to non-intubated patients. Patients under non-invasive respiratory support might present with high transpulmonary pressures, pulmonary strain and pendelluft, which contribute to the development of patient self-inflicted lung injury (P-SILI). Previous studies have identified that continuous positive airway pressure (CPAP) is successful in attenuating P-SILI effectors compared to high flow nasal oxygenation (HFNO). However, it remains uncertain whether this attenuation actually results into a reduction in lung injury and improved clinical outcomes.

This is a multicentre, randomised, open-label, controlled trial. 120 non-intubated patients with established ARDS will be randomly assigned to receive non-invasive respiratory support with either CPAP 12 cmH2O or HFNO 50 L/min for 48 hours plus standard intensive care. The primary outcome is biological lung injury evaluated through the epithelial pulmonary dysfunction biomarker sRAGE (soluble Receptor of Advanced Glycation End-products). Secondary outcomes include plasmatic pulmonary dysfunction biomarkers (angiotensin-II, interleukin-6, interleukin-10), P-SILI effectors (pulmonary strain, pendelluft, transpulmonary pressure), 48-hour traqueal intubation rate, 90-day traqueal intubation rate and 90-day mortality. All analyses will be conducted according to the intention-to-treat principle.

This study will assess the potential role of CPAP in attenuating P-SILI effectors and inflicting less biological lung injury compared to HFNO. This physiologic effect may lead to lower rates of traqueal intubation and mortality. This project will provide new knowledge on the respiratory management of non-intubated ARDS patients, a subject where evidence is lacking.

Inclusion criteria

• PaO2/FiO2 ratio <300 mmHg with FiO2 >40% and PEEP ≥5 cmH2O (CPAP) or flow ≥30 L/min (HFNC).
• Bilateral pulmonary opacities observed in the chest X-ray, thoracic computerized tomography (CT) scan or lung ultrasonography (bilateral B lines)
• <7 days from the pulmonary insult to symptom onset and criteria 1 and 2
• Not meeting the aforementioned criteria for >24 hours prior to study inclusion.

Exclusion criteria

• Age <18 years or >80 years
• History of chronic respiratory failure or interstitial pulmonary disease
• Acute cardiogenic pulmonary edema after echocardiographic evaluation
• Having received either invasive mechanical ventilation or non-invasive mechanical ventilation (NIV)
• Atelectasis, pleural effusion, pulmonary masses or nodules as the primary finding in thoracic imaging.
• "Do not intubate, do not resuscitate" orders
• Presenting significant nasal obstruction.