The optimal noninvasive respiratory support for acute hypoxemic respiratory failure is debated. Recent preliminary data indicate that both pressure-support noninvasive ventilation (NIV) and continuous-positive airway pressure (CPAP) may be of benefit. While often applied interchangeably in clinical practice, NIV and CPAP have different effects on the inspiratory effort, which is the major determinant of self-inflicted lung injury. Also, inspiratory effort widely varies among individuals.

The purpose of this study is to assess the physiological effects of a noninvasive respiratory support approach guided by inspiratory effort, as compared to CPAP and NIV, in patients with moderate-to-severe acute hypoxemic respiratory failure.

Patients with acute hypoxemic respiratory failure will undergo a decremental pressure-support trial during helmet noninvasive support. The following pressure-support settings will be applied sequentially, with positive end-expiratory pressure kept constant and equal to 10-12 cmH2O: 20 cmH2O, 16 cmH2O, 12 cmH2O, 8 cmH2O and high-flow-driven CPAP. Inspiratory effort will be monitored during the trial through esophageal manometry. The personalized setting of noninvasive support will be defined as the minimal pressure-support level capable of generating inspiratory effort between 5 and 10 cmH2O.

Personalized noninvasive support will be then compared to conventionally-set NIV and CPAP in a randomized cross-over trial.

Inclusion Criteria:

• Acute hypoxemic respiratory failure and PaO2/FiO2<200 mmHg
• PaCO2<45 mmHg
• Respiratory failure not caused by exacerbation of chronic pulmonary disease, cardiac failure or fluid overload

Exclusion Criteria:

• Pregnancy
• Contraindication to helmet support
• Contraindication to esophageal manometry
• Contraindication to electrical-impedance tomography monitoring
• Recent surgery involving the abdomen or the thorax
• Pneumothorax or documented barotrauma

Data will be made available upon reasonable request