Effects of PERMISSive Lung-protective Ventilation on Outcome in Critically Ill Invasively Ventilated Patients

Inclusion Criteria: * admission to one of the participating ICUs; * intubated and receiving invasive ventilation with an expected duration of ventilation of at least 24 hours. Exclusion Criteria: * age below 18 years; * receiving invasive ventilation \> 1 hour in the ICU, or receiving invasive ventilation \> 6 hours directly preceding the current ICU admission (i.e., in the operating room or in the emergency department); * receiving or planned to receive veno-venous, veno-arterial or arterio-venous extracorporeal membrane oxygenation (ECMO); * having COPD GOLD III and IV; * contra-indication 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 brain injury, judged by the attending physician; * 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; * suspected or confirmed pregnancy; * participation in another interventional trial using similar endpoints; * previously randomized in this study; * no informed consent; or * admitted for terminal care