The goal of this physiological intervention study is to unravel the (patho)physiological mechanisms and potential clinical benefits of a pre-specified early switch from controlled to assisted ventilation in mechanically ventilated adult patients with acute hypoxemic respiratory failure (PaO2/FiO2 ratio < 200 mmHg).

The intervention is that participants will be switched from controlled to assisted ventilation when PaO2/FiO2 ratio > 200 mmHg.

The primary endpoint is the change in regional lung stress (as derived by electrical impedance tomography) when switching from controlled to assisted ventilation and until a successful or failed switch.

A crucial milestone in the trajectory of the mechanically ventilated patient is the switch from fully controlled mechanical ventilation to assisted ventilation. This switch should be made as early as feasible and safe, to limit the detrimental effects from prolonged controlled ventilation and sedation. However, there is also indirect evidence that excessive breathing effort during assisted ventilation may worsen lung injury (P-SILI). There are no guidelines that address this important switch moment.

Therefore, the overall aim of this physiological intervention study is to unravel the (patho)physiological mechanisms and potential clinical benefits of a pre-specified early switch from controlled to assisted ventilation in mechanically ventilated adult patients with acute hypoxemic respiratory failure (PaO2/FiO2 ratio < 200 mmHg).

Participants will be switched from controlled to assisted ventilation switch when PaO2/FiO2 ratio > 200 mmHg and will be monitored continuously using electrical impedance tomography, and oesophageal and gastric pressure until 4 hours post-switch and twice daily for 72 hours or until switch failure (switch back to controlled ventilation within 72 hours).

The primary endpoint is the change in regional lung stress (as derived by electrical impedance tomography) when switching from controlled to assisted ventilation and until a successful or failed switch.

Inclusion Criteria:

• 18 years old
• Written informed consent from a legal representative
• Mechanical ventilation via an endotracheal tube
• Acute hypoxemic respiratory failure with PaO2/FiO2 ratio < 200 mmHg
• Under continuous sedation with or without paralysis

Exclusion Criteria:

• Expected mechanical ventilation duration of <48 hours
• Pure chronic obstructive pulmonary disease exacerbation
• Pre-existent respiratory muscle disease
• Contraindication to EIT monitoring (as per clinical protocol, e.g. pacemaker, burns or thoracic wounds limiting electrode placement)
• Contra-indications to oesophageal manometry (as per clinical protocol, e.g., recent oesophageal surgery, oesophageal varices, severe bleeding disorders)
• Known pregnancy
• Anticipating withdrawal of life support and/or shift to palliation as the goal of care