Prospective, observational, monocentric study to assess the physiological effects of dexmedetomidine and remifentanil in spontaneously breathing patients with acute hypoxemic respiratory failure receiving high-flow nasal oxygen.

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.

Inclusion Criteria:

• Age ≥18 years
• PaO2/FiO2 ratio ≤ 200;
• PaCO2 < 45 mmHg;
• At least one symptom prompting the use of sedative-analgesic drugs according to the prescription of the attending physician: dyspnea and/or discomfort equal of greater than 4/10 (Visual Analog Scale - VAS), respiratory rate equal or greater than 25 breaths per minute, PaCO2<35 mmHg, pain (Numeric Rating Scale ≥ 4 or Behavioral Pain Scale - Non-Intubated ≥ 4);
• Informed consent signature.

Exclusion Criteria:

• Pregnancy;
• Exacerbation of asthma or chronic obstructive pulmonary disease;
• Chronic lung disease, requiring oxygen therapy at home;
• Cardiogenic pulmonary oedema;
• Hemodynamic instability (systolic blood pressure <90 mmHg or mean arterial pressure <65 mmHg) and/or lactic acidosis (lactate >5 mmol/L) and/or clinically diagnosed shock;
• Metabolic acidosis (pH <7.30 with normal or hypocarbia);
• Glasgow Coma Scale <13;
• Contraindications to esophageal balloon and/or EIT placement.

Patients with hypoxemic respiratory failure treated with high-flow oxygen therapy for whom the attending physician, based on clinical indications, has decided to initiate sedative-analgesic treatment with dexmedetomidine or remifentanil.

The study plans to enroll 40 patients, including 20 patients treated with dexmedetomidine and 20 patients treated with remifentanil.