About this trial

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).

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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).

Disqualifiers

Pre-existent neuromuscular disease

History of chronic respiratory failure requiring long-term oxygen therapy

Muscle paralysis

Pneumothorax

Trial design

Design model

Single group

Treatments tested in this trial

PEEP level changes
Other 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.

Treatment groups

20 Participants

are divided into 1 treatment group

Group A: Single armExperimental treatment 1 intervention

Trial outcomes

Primary outcomes

1

PEEP-related changes in diaphragm neuromechanical efficiency (NME)

The primary endpoint of this study will be the evaluation of PEEP-induced changes in diaphragm neuromechanical efficiency (NME, cmH2O/µV), calculated as the ratio between the change in transdiaphragmatic pressure (representing inspiratory effort in cmH2O and assessed through the use of esophageal and gastric manometry) and the change in diaphragm electrical activity (neural respiratory drive, expressed in µV and measured through diaphragm EMG by a dedicated nasogastric tube) for each inspiration (ΔPdi/ΔEAdi). NME is an index of diaphragm efficiency and of potential electromechanical uncoupling, a key PEEP-mediated effect on the diaphragm. Its assessment combines changes in neural respiratory drive and inspiratory effort after a change in PEEP, which will be assessed individually and combined as a ratio as primary outcome.

Time frame