Airway Occlusion Measured During Non-invasive Ventilation to Assess Respiratory Effort

Study Overview
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Brief Summary
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Non-invasive ventilation (NIV) is extensively used in critical care settings and emergency departments for a variety of aetiologies but specially for acute respiratory failure (ARF). It eliminates morbidity related to the endotracheal tube and use of sedatives so it reduces intensive care unit (ICU) complications; however, on the other hand, the harmful effects of spontaneous breathing through the intensity of inspiratory effort may predispose the patient to the onset of self-inflicted lung injury (SILI). Therefore, measuring the level of inspiratory effort is recommended.The aim of this proof-of-concept physiological study was to describe the correlation between ΔPocc measured on the ventilator and ΔPes in healthy subjects with NIV.

Detailed Description
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Non-invasive ventilation (NIV) is extensively used in critical care settings and emergency departments for a variety of aetiologies but specially for acute respiratory failure (ARF). Recommendations based on the GRADE methodology were addressed on several conditions such as exacerbation of chronic obstructive pulmonary disease (COPD), cardiogenic pulmonary oedema, de novo hypoxaemic respiratory failure, immunocompromised patients, chest trauma, palliative care, post-operative care, weaning and post-extubation period. NIV eliminates morbidity related to the endotracheal tube and use of sedatives so it reduces intensive care unit (ICU) acquired pneumonia, diaphragmatic atrophy, ICU acquired weakness and delirium. On the other hand, the harmful effects of spontaneous breathing through the intensity of inspiratory effort may follow a critical increase in respiratory drive, thus producing uncontrolled tidal change in dynamic transpulmonary pressure (PLdyn) that would increase the risk of injury to the dependent lung and predispose the patient to the onset of self-inflicted lung injury (SILI). High positive end-expiratory pressure (PEEP) renders spontaneous effort non injurious. P-SILI may worsen the clinical outcome of patients who require endotracheal intubation after having received noninvasive respiratory support. The underlying mechanisms of SILI are heterogeneous and include the pendelluft phenomenon, increased transvascular pressure gradient aggravating alveolar damage, excessive diaphragmatic loading with impaired systemic oxygen delivery and muscle injury. Therefore, measuring the level of inspiratory effort is recommended. Esophageal manometry is a precise estimate of the changes in pleural pressure and is considered the gold standard to measure respiratory effort. Tonelli et al. measured tidal change in esophageal pressure (ΔPes) in patients with acute hypoxic de novo respiratory failure on NIV and demonstrated a median baseline value of ΔPes of 34 cmH2O that was significantly reduced within the first 2 hours of ventilation in patients who were successful in the NIV trial, whereas those failing the NIV trial did not show a significant reduction. However, esophageal manometry is rarely available bedside in acute settings on severe patients with respiratory distress so other ways of measuring inspiratory effort have been assessed, such as nasal pressure swings or the patient's respiratory effort against the occluded airway (ΔPocc). The latest was demonstrated on invasive mechanical ventilation patients. Lopez Navas et al. tried to correlate the inspiratory pressure-time product (PTPinsp) from transdiaphragmatic pressure to a novel expiratory occlusion method of 0.2 s in healthy volunteers with NIV on different settings; however, their results through Bland-Altman analysis of PTPinsp revealed mean differences between -4.22 and 7.57 cmH2O (SD 0.77- 8.52) and considerable differences between subjects. Moreover, Dargent A, et al. explored the feasibility of a noninvasive respiratory drive evaluation using ventilator-derived data as P0.1, clinical information and diaphragm ultrasound in COVID 19 patients on CPAP session with 5 cmH2O. They showed that P0.1 was achievable during NIV with a median value of 4.4 [2.7-5.1] cmH2O and not correlated with leaks, though they were small (5 [4-7] l/min); nevertheless, P0.1 was not accurate at predicting the risk of intubation but it was limited by its small sample size. In addition, P0.1 has been previously evaluated (with other physiological parameters) on NIV in COPD patients to predict post-extubation respiratory distress. They reported that only P0.1 recorded 1 h after the discontinuation of mechanical ventilation followed by 30 minutes of 4 cmH2O pressure support ventilation, was significantly different between the patients with and without respiratory distress (4.2 vs 1.8, p < 0.01). Nonetheless, there are no studies that measured bedside the pressure generated by the respiratory muscles during NIV. The aim of this proof-of-concept physiological study was to describe the correlation between ΔPocc measured on the ventilator and ΔPes in healthy subjects with NIV.

Official Title
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Airway Occlusion Measured During Non-invasive Ventilation to Assess Respiratory Effort

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Diagnostic Test: airway pressure occlusion measurement


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy subjects over 18 years old who wish to participate were included. Exclusion Criteria: Exclusion criteria was the presence of any esophageal disease or COPD.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Study Plan
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How is the study designed?
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Arms and Interventions

| Intervention/Treatment |
| --- |
|Diagnostic Test: airway pressure occlusion measurement|Flow, airway pressure (Paw), and esophageal pressure (Pes) will be recorded for 10 minutes on different NIV settings: during each one, three end-expiratory airway occlusions will be applied at random intervals. Each occlusion was maintained for the duration of a single breath deflection in Paw from PEEP, confirmed by the return of Paw to baseline.|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Correlation between Poccvent and Pesflux | The primary outcome was the correlation between the ΔPoccvent and ΔPesflux on each ventilator setting as independent measures and the agreement between two sets of measurements on each ventilator setting. | The subjects will be measured on each ventilator setting (3 settings) for 10 minutes. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Correlation between Pccvent and PTPmus | The secondary outcome was the correlation between ΔPoccvent the mean PTPmus during the last minute of ventilation for each ventilator setting. | The subjects will be measured on each ventilator setting (3 settings) for 10 minutes. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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non invasive ventilation, occlusion airway pressure