PERMISSive Lung-protective Ventilation RCT

Inclusion Criteria: * admission to one of the participating intensive care units (ICUs); * intubated and receiving invasive ventilation; and * expected duration of ventilation of at least 24 hours (based on ICU admission diagnosis and clinical judgment). Exclusion Criteria: * age below 18 years; * invasive ventilation before randomization \> 2 hours in the ICU or invasive ventilation \> 6 hours in the operating room or emergency department directly preceding the current ICU admission; * receiving or planned to receive veno-venous, veno-arterial or arterio-venous extracorporeal membrane oxygenation (ECMO); * contraindications for hypercapnia, such as ongoing cardiac ischemia (as defined in the guideline of the European Society of Cardiology), or having suspected or confirmed increased intracranial pressure due to (traumatic) brain injury, judged by the attending physician; * having severe Chronic Obstructive Pulmonary Disease (COPD); GOLD classification III or IV or classified in group B or E of the GOLD ABE assessment tool); * after cardiac arrest; * suspected or confirmed pregnancy; * having any neurologic diagnosis that can prolong duration of mechanical ventilation, e.g., Guillain-Barré syndrome, high spinal cord lesion or amyotrophic lateral sclerosis, multiple sclerosis, or myasthenia gravis; * participation in another interventional trial using similar endpoints; * previous randomization in this study; * no informed consent or; * admitted for palliative and terminal care.