Rationale:

In patients with acute hypoxemic respiratory failure (AHRF), preserving spontaneous breathing during mechanical ventilation offers physiological benefits, but also carries risks. While spontaneous breathing improves gas exchange and limits diaphragm atrophy, strong inspiratory efforts may worsen lung and diaphragm injury. Balancing these factors requires refined and tailored strategies, such as the modulation of PEEP. However, the impact of PEEP on neural respiratory drive and inspiratory effort is very heterogenous, and these two entities have only been studied separately in limited subsets of patients and healthy subjects. Additionally, it remains unclear whether the major determinant of PEEP-induced changes in respiratory drive and effort is represented by variations in diaphragm geometry, lung compliance, or by the presence of expiratory muscles recruitment, which may counteract its effect.

Objective:

The primary objective is to determine the effect of PEEP on diaphragm neuromechanical efficiency (i.e. an index of neural respiratory drive and inspiratory effort) in patients with acute hypoxemic respiratory failure during invasive assisted mechanical ventilation. The secondary objective is to determine the major physiological contributors to PEEP-mediated changes in diaphragm neuromechanical efficiency.

Study design: Prospective, physiological study. Study population: Invasively mechanically ventilated adult patients admitted to the ICU.

Intervention:

For each patient, six different PEEP levels (15-12-10-8-5-2 cmH2O) will be tested during a decremental PEEP trial. During each step, neural respiratory drive, inspiratory effort, expiratory muscle activity, lung inflation pattern through electrical impedance tomography, respiratory muscle geometry and function through ultrasound and surface EMG, gas exchange and hemodynamics data will be collected.

Main study parameters/endpoints:

The primary outcome of the study will be the evaluation of PEEP-mediated changes in diaphragm neuromechanical efficiency (NME).

Inclusion Criteria:

• Age > 18 years
• Acute hypoxemic respiratory failure (AHRF) with a PaO2/FiO2-ratio ≤ 200
• Patient on invasive assisted mechanical ventilation in pressure support mode exhibiting valid inspiratory efforts (occlusion pressure > 5 cmH2O).

Exclusion Criteria:

• Pre-existent neuromuscular disease
• History of chronic respiratory failure requiring long-term oxygen therapy
• Muscle paralysis
• Pneumothorax
• Contra-indication to EIT monitoring (e.g. burns, pacemaker, thoracic wounds limiting electrode placement)
• Contra-indications for EAdi or oesophageal balloon catheter placement (e.g. history of gastric bypass surgery, gastro-oesophageal junction surgery, oesophageal stricture, recent upper gastrointestinal hemorrhage or known/suspected varices).