Supported Ventilation in ARDS Patients

Study Overview
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Brief Summary
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Acute respiratory distress syndrome (ARDS) is characterized by acute bilateral pulmonary infiltrates and impairment of oxygen uptake. For example, pneumonia can cause the development of ARDS. Despite modern intensive care treatment, mortality in ARDS patients remains high (40%). Invasive mechanical ventilation (MV) is the mainstay of ARDS treatment. Controlled MV is the conventional ventilation strategy to ensure lung protective ventilation (low tidal volumes) and recovery of the lungs. However, among disadvantages of controlled MV are the development of respiratory muscle atrophy (due to disuse) and the need for high dose sedatives to prevent patient-ventilator asynchrony. The use of high doses of sedatives and respiratory muscle weakness are associated with increased morbidity, worse clinical outcomes and prolonged MV. Besides controlled MV, a patient can be ventilated with supported ventilation. Supported MV decreases the likelihood to develop muscle atrophy, improves oxygenation and hemodynamics, and lowers consumption of sedatives. However potential disadvantages of supported ventilation include generation of too high tidal volumes, especially in patients with high respiratory drive. A previous study in healthy subjects has shown that titration of neuromuscular blocking agent (NMBA) can decrease activity of inspiratory muscles, while maintaining adequate ventilation. It is hypothesized that low dose NMBA may enable supported MV with adequate tidal volumes, in patients with high respiratory drive.

Official Title
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Reducing High Respiratory Drive to Facilitate Supported Ventilation in ARDS Patients: a Pilot Study

Conditions
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Acute Respiratory Distress Syndrome, Mechanical Ventilation, Tidal Volume

Intervention / Treatment
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* Drug: Rocuronium


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: age > 18 year informed consent ARDS according to the Berlin definition RASS -4/-5 tidal volume > 8 ml/kg during supported ventilation double balloon esophageal EMG NAVA catheter Exclusion Criteria: recent use of muscle relaxants / NMBAs (< 3 hours) pre-existent neuromuscular disease (congenital or acquired) or diseases / disorders know to be associated with myopathy including auto-immune diseases phrenic nerve lesions elevated intracranial pressure or clinical suspicion of elevated intracranial pressure (i.e. neurotrauma) open chest or abdomen pregnancy systolic blood pressure < 90 mm Hg / MAP < 65 mm Hg

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: Prevention
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Neuromuscular blocking agent<br> | Drug: Rocuronium<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Feasibility of titrating tidal volume < 6 ml/kg | The feasibility of titrating tidal volume in ARDS patients below 6 ml/kg using NMBA is evaluated in every patient. The outcome measure is dichotomic (yes/no). | Within 5 minutes after titration of NMBA | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Respiratory rate | A secondary outcome measure is the respiratory rate after titration NMBA during different ventilatory modes. | Artefact-free period in the first 15 minutes during different ventilatory modes after titration of NMBA | 
| Diaphragm electrical activity | A secondary outcome measure is the root-mean-square of the diaphragm electrical activity after titration NMBA during different ventilatory modes. | Artefact-free period in the first 15 minutes during different ventilatory modes after titration of NMBA. | 
| Transpulmonary pressure | Transpulmonary pressure is determined as the difference between mouth pressure and esophageal pressure during inspiration. Breath-by-breath data are ensemble-averaged over the first 2 minutes after titration NMBA during different ventilatory modes. | Artefact-free period in the first 15 minutes during different ventilatory modes after titration of NMBA. | 
| Transdiaphragmatic pressure | Transdiaphragmatic pressure is determined as the difference between gastric pressure and esophageal pressure during inspiration. Breath-by-breath data are ensemble-averaged over the first two minutes after titration NMBA during different ventilatory modes. | Artefact-free period in the first 15 minutes during different ventilatory modes after titration of NMBA. | 
| Neuroventilatory efficiency | A secondary outcome measure is the neuroventilatory efficiency (i.e. the ratio of diaphragm electrical activity and tidal volume) after titration NMBA during different ventilatory modes. | Artefact-free period in the first 15 minutes during different ventilatory modes after titration of NMBA. | 
| Neuromechanical efficiency | A secondary outcome measure is the neuromechanical efficiency (i.e. the ratio of diaphragm electrical activity and transdiaphragmatic pressure) of the diaphragm after titration NMBA during different ventilatory modes. | Artefact-free period in the first 15 minutes during different ventilatory modes after titration of NMBA. | 
| Patient-ventilator contribution to breathing | A secondary outcome measure is the patient-ventilator contribution to breathing (i.e. ratio of: the ratio of tidal volume and diaphragm electrical activity without assist, and the ratio of tidal volume and diaphragm electrical acticity with assist) during and after titration of NMBA. | During titration of NMBA (each three minutes) and during PS and NAVA after titration NMBA | 
| Oxygenation index | A secondary parameter is the oxygenation index which is determined as the ratio between arterial oxygen tension and fraction of inspired oxygen. | Before start of the study; before titration of NMBA during different ventilatory modes; after titration of NMBA; after an hour for each ventilatory mode. | 
| Carbon dioxide tension in arterial blood (PaCO2) | A secondary parameter is the carbon dioxide tension in arterial blood. | Before start of the study; before titration of NMBA during different ventilatory modes; after titration of NMBA; after an hour for each ventilatory mode. | 
| pH of arterial blood | A secondary parameter is the pH of arterial blood. | Before start of the study; before titration of NMBA during different ventilatory modes; after titration of NMBA; after an hour for each ventilatory mode. | 
| Patient-ventilator interaction | Patient-ventilator interaction is evaluated using the NeuroSync index during different ventilatory modes. | Artefact-free period in the first 15 minutes during different ventilatory modes after titration of NMBA. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Tidal volume, ARDS, Mechanical Ventilation, NMBA