Physiological Effects of Continuous Negative External Pressure for Acute Hypoxemic Respiratory Failure

This study is a prospective randomized cross-over trial. Eligible, consenting participants will undergo 4 strategies of respiratory support: high-flow nasal cannula (HFNC) only, HFNC + continuous negative external pressure (CNEP) of 10 cmH2O, HFNC + CNEP of 20 cmH2O, HFNC + CNEP of 30 cmH2O. Throughout the study period, HFNC will be managed at a constant flow rate with fraction of inspired oxygen (FiO2) titrated to achieve goal oxygen saturation (SpO2) of 90-97%, measured via continuous pulse-oximetry. Each of the 4 strategies will be performed for 45 minutes per strategy, interspersed with a 15-minute washout period of HFNC only. Participants will be randomized to the sequence of strategies for respiratory support.

A summary of the sequence of trial procedures is as follows:

• Perform baseline measures.
• Wait 5-10 minutes for recovery.
• Initiate first random treatment assignment for up to 45 minutes.
• HFNC-only washout for 15 minutes
• Initiate second random treatment assignment for up to 45 minutes.
• HFNC-only washout for 15 minutes
• Initiate third random treatment assignment for up to 45 minutes.
• HFNC-only washout for 15 minutes
• Initiate fourth random treatment assignment for up to 45 minutes.
• Return to usual care (HFNC only)

If a participant does not tolerate a given level of CNEP, the patient will be returned to HFNC for 5 minutes and then given the option to attempt that CNEP level again. If the patient declines reattempt or does not tolerate that CNEP level on reattempt, the HFNC-only washout will be instituted for 15 minutes before proceeding to the next protocol step.

Inclusion criteria

• Age 18 years or older
• Acute hypoxemic respiratory failure
• Non-cardiogenic airspace opacities on chest radiograph or computed tomography (CT) scan
• High-flow nasal cannula (flow ≥ 30 LPM) initiated within last 96 hours (4 days)
• FiO2 ≥ 40%
• SpO2 ≥ 92%

Exclusion criteria

• Do-not-intubate order
• Anatomical factor predisposing to poor fit of cuirass (e.g. severe kyphosis or scoliosis)
• Use of cuirass precluded, e.g. due to:

• Clinically prescribed prone positioning
• Tense ascites
• Severe abdominal pain
• Abdominal wound or surgery
• Pregnancy
• Agitated delirium
• Prior intubation during hospital stay
• Cardiogenic pulmonary edema
• Exacerbation of asthma or COPD
• Chronic lung disease, including:

• Interstitial lung disease
• Cystic fibrosis
• Lung mass, lung cancer, or metastasis to the lung
• Lung transplant recipient
• Any disease that requires home oxygen
• Glasgow coma score < 15
• Chest tube, pneumothorax, or pneumomediastinum
• Hemodynamic instability (mean arterial pressure < 55 mmHg or norepinephrine-equivalent vasopressor requirement > 0.1mcg/kg/min)
• Implantable electrical device (e.g. pacemaker, defibrillator, neurostimulator)
• Unreliable pulse-oximetry tracing
• Imminent intubation
• Anticipated lack of patient availability to complete study procedures (e.g. due to planned clinical procedure such as CT scan or dialysis during potential time of study)
• Attending physician refusal