AHRF
Conditions
Brief summary
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.
Detailed description
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.
Interventions
None listed
Sponsors
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Study design
Observational model
OTHER
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Inspiratory effort, expressed in cmH2O | During procedure | Negative deflection in esophageal pressure during inspiration |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Tidal volume distribution | During procedure | Tidal volume distribution in the different lung regions (ventral-midventral-middorsal-dorsal), assessed with electrical impedance tomography |
| End-expiratory lung volume | During procedure | Global impedance-derived end-expiratory lung volume (EELI), measured with electrical impedance tomography |
| Regional End-expiratory lung volume | During procedure | Regional (ventral-midventral-middorsal-dorsal) impedance-derived end-expiratory lung volume (EELI), measured with electrical impedance tomography |
| Dynamic transpulmonary driving pressure | During procedure | Tidal change in transpulmonary pressure assessed with esophageal catether |
| Global impedance-derived lung dynamic strain | During procedure | Change in impedance due to tidal volume / end expiratory lung impedance, both measured with electrical impedance tomography |
| Regional impedance-derived lung dynamic strain | During procedure | Change in impedance due to tidal volume / end expiratory lung impedance in the four regions of the lungs (ventral, mid-ventral, mid-dorsal, dorsal), measured with electrical impedance tomography |
| Pendelluft | During procedure | Occurrence of intra-tidal shift of gas within different lung regions at beginning of inspiration |
| Work of breathing | During procedure | Esophageal pressure simplified pressure time product per minute |
| Dyspnea | During procedure | Defined according to visual analog scale of dyspnea (0-10, where 10 represents worst perceivable dyspnea) |
| Discomfort | During procedure | Defined according to visual analog scale of discomfort (0-10, where 10 represents worst perceivable discomfort). |
| PaO2/FiO2 ratio | During procedure | Change in arterial Pa/FiO2 (in mmHg) |
| Recuitment of expiratory muscles, expressed in cmH2O of gastric pressure | During procedure | Expiratory increases in gastric pressure |
| Respiratory rate | During procedure | Change in respiratory rate (breaths/minute) |
Countries
Italy
Contacts
CONTACTDomenico Luca Grieco, MD
CONTACTGaia Tempo, MD
Outcome results
None listed