Neural Pressure Support for Low Pulmonary Compliance

Study Overview
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Brief Summary
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With this interventional prospective study, we aim at comparing the effectiveness of Neural Pressure Support (NPS) in reducing respiratory work and patient-ventilator asynchronies as compared with standard Pressure Support Ventilation (PSV), in a cohort of patients with Acute Respiratory Failure (ARF) and low respiratory system compliance.

Detailed Description
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Acute respiratory failure (ARF) is a critical condition caused by impaired function of the lungs.1,2 The cornerstone of ARF management is invasive mechanical ventilation (IMV).3,4 Unfortunately, despite lifesaving, IMV is associated with several side effects (e.g., ventilator-associated pneumonia, ventilator associate induced lung injury, diaphragmatic dysfunction), and thus liberation from invasive mechanical ventilation is an everyday effort for critical care physicians.5 Pressure support ventilation (PSV) is one of the most widely used mechanical ventilation modes for liberation from IMV.6 PSV is a partial ventilatory mode: the ventilator and the patient co-operate to generate the inspiratory and expiratory pressures, flows, and volumes. During conventional PSV, the initiation of the breath is triggered by a reduction in expiratory pressure or a drop in expiratory flow.7 The termination of the breath occurs when the inspiratory flow falls to a predetermined fraction of the peak inspiratory flow.8 The main goal of mechanical ventilation is to help restore gas exchange and reduce the work of breathing (WOB) by assisting respiratory muscle activity.9 Knowing the determinants of WOB is essential for the effective use of mechanical ventilation and also to assess patient readiness for weaning. To reduce WOB, PSV needs to be synchronous and smooth interaction should happen between the ventilator and the respiratory muscles.10 Ideally, the ventilator trigger and cycling should coincide with the beginning and end of the patient's inspiratory effort.11 However, patient-ventilator asynchrony is common during PSV,12,13 thereby contributing to an increased work of breathing and an increased duration of mechanical ventilation.14 An important objective of assisted or patient-triggered mechanical ventilation is to avoid ventilator-induced diaphragmatic dysfunction by allowing the patient to generate spontaneous efforts.15 A second objective is to reduce the patient's work of breathing by delivering a sufficient level of ventilatory support.16 Finally, intuition suggests that a good match between patient respiratory efforts and ventilator breaths optimizes patient comfort and reduces work of breathing.17 Patient-ventilator asynchrony can be defined as a mismatch between the patient and ventilator inspiratory and expiratory times.18 Although inspiratory and expiratory delays are almost inevitable with most ventilatory modes, several patterns of major asynchrony exist and can be easily detected by clinicians.14 The diaphragmatic electrical activity (EAdi) can be used to optimize the ventilator settings and improve the matching between patient and ventilator. The EAdi signal is a surrogate of respiratory brain stem output and can be recorded using specialized nasogastric tubes equipped with electrodes.19 The Neural Pressure Support (NPS) is a newer ventilation mode that includes neural trigger and termination of inspiration based on the electrical activity of the diaphragm (Edi). NPS delivers a constant airway pressure support independent of the patient's efforts.20 The NPS may be particularly beneficial for ARF patients with lower respiratory compliance. Indeed, in this cohort, during standard PSV, expiratory cycling may be hampered by several asynchronies.21 However, to our knowledge, the effectiveness of NPS in reducing asynchronies and respiratory work has not been tested and compared with standard PSV in patients with low respiratory system compliance.

Official Title
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Neural Pressure Support for Low Pulmonary Compliance

Conditions
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Acute Respiratory Failure

Intervention / Treatment
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* Device: Neural Pressure Support
* Drug: Pressure Support Ventilation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age > 18 years Admission to Intensive Care Unit (ICU) for ARF Low compliance of the respiratory system (Crs ≤ 30 ml/cmH2O) Written informed consent obtained Exclusion Criteria: Contraindication to nasogastric tube insertion (gastroesophageal surgery in the previous 3 months, gastroesophageal bleeding in the previous 30 days, history of esophageal varices, facial trauma) Increased risk of bleeding with nasogastric tube insertion, due to severe coagulation disorders and severe thrombocytopenia ( i.e., International Normalized Ratio (INR) > 2 and platelets count < 70.000/mm3) Severe hemodynamic instability (noradrenaline > 0.3 μg/kg/min and/or use of vasopressin) Failure to obtain a stable EAdi signal Central nervous system or neuromuscular disorders Moribund status

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: This is an interventional prospective crossover physiological study that will take place at the Intensive Care Unit E. Vecla, Department of Anesthesia, Intensive Care and Emergency, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NPS<br>To evaluate WOB and asynchronies in patients with low respiratory system compliance undergoing Neural Pressure Support Ventilation. | Device: Neural Pressure Support<br>* To evaluate WOB and asynchronies in patients with low respiratory system compliance undergoing either PSV and NPS.<br>Drug: Pressure Support Ventilation<br>* To evaluate WOB and asynchronies in patients with low respiratory system compliance undergoing either PSV and NPS.<br>|
| Sham Comparator: PSV<br>To evaluate WOB and asynchronies in patients with low respiratory system compliance undergoing Pressure Support Ventilation. | Device: Neural Pressure Support<br>* To evaluate WOB and asynchronies in patients with low respiratory system compliance undergoing either PSV and NPS.<br>Drug: Pressure Support Ventilation<br>* To evaluate WOB and asynchronies in patients with low respiratory system compliance undergoing either PSV and NPS.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Work Of Breathing (WOB) | We hypothesize that Neural Pressure Support (NPS) is able to improve the patient-ventilator interaction, thus reducing significantly the patient's work of breathing (WOB). WOB will be evaluated by the off-line analysis of the esophageal pressure waveform. | 30 minutes ventilatory traces recording | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Asynchronies | We hypothesize that Neural Pressure Support (NPS) is able to improve the patient-ventilator interaction, thus reducing significantly the asynchronies between patient and ventilator. Asynchronies will be estimated by the Asynchrony Index (AI) calculated off-line by ventilatory waveforms analysis. | 30 minutes ventilatory traces recording | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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NPS, WOB, AI