Optimization of Respiratory Effort With Titrated Sedation in Patients With Acute Hypoxemic Respiratory Failure - The OPTIREST Study

Sedation in spontaneously breathing hypoxemic patients represents a critical physiological trade-off between lung protection and maintenance of adequate ventilation. While spontaneous breathing is generally encouraged to preserve diaphragm function and avoid invasive ventilation, excessive respiratory drive may promote patient self-inflicted lung injury (P-SILI) through increased inspiratory effort, elevated transpulmonary pressure swings, pendelluft phenomena, and regional stress amplification. Conversely, excessive sedation may suppress respiratory drive, resulting in hypoventilation, impaired gas exchange, and diaphragm disuse. Sedation therefore behaves as a double-edged sword, requiring careful titration to balance lung protection and adequate ventilation. Despite the widespread use of dexmedetomidine and remifentanil in this setting, limited information is available regarding their dose-dependent physiological effects on inspiratory effort, transpulmonary pressure, regional ventilation distribution, expiratory muscle recruitment, and lung stress. Current clinical practice relies mainly on symptom control (dyspnea, agitation, tachypnea) without direct assessment of the mechanical and regional effects of sedation on the injured lung; consequently, sedation strategies remain largely empirical and poorly standardized. The study aims to characterize the effects of sedation administered through Target-Controlled Infusion (TCI) on respiratory mechanics and regional lung behavior in spontaneously breathing patients receiving high-flow nasal oxygen. By integrating esophageal pressure monitoring and electrical impedance tomography, the effects of increasing effect-site concentrations of dexmedetomidine or remifentanil on inspiratory effort and its regional consequences will be investigated.