Feasibility of Reducing Respiratory Drive Using the Through-flow System (Throughflow)

Feasibility of Reducing Respiratory Drive in Patients With Acute Hypoxemic Respiratory Failure Using the Through-flow System

Mechanical ventilation can lead to diaphragm and lung injury. During mechanical ventilation, the diaphragm could be completely rested or it could be overworked, either of which may cause diaphragm injury. Mechanical stress and strain applied by mechanical ventilation or by the patient's own respiratory muscles can also cause injury to the lungs. Diaphragm and lung injury are associated with increased morbidity and mortality. Throughflow is a novel system that can reduce dead space without the need to increase the tidal ventilation, reducing the ventilatory demands and respiratory drive.

Patients with acute respiratory failure often develop significant diaphragm weakness during mechanical ventilation. Diaphragm weakness is associated with prolonged duration of mechanical ventilation and higher risk of death. Clinical data and experimental evidence indicate that the ventilator injures the diaphragm via two opposing mechanisms, disuse and excessive loading. Cessation of diaphragm activity leads to rapid disuse atrophy within hours. On the other hand, high inspiratory loads result in myofibril edema, inflammation and contractile dysfunction. In light of this, studies found that patients with an intermediate level of inspiratory effort, similar to that of healthy subjects breathing at rest, exhibited the shortest duration of ventilation. Arterial CO2 (PaCO2) tension and physiological dead space play an important role in determining the ventilatory requirements and respiratory drive in patients with AHRF. Throughflow (Neurovent) is a novel system that reduces anatomical dead space by providing a constant flow of fresh gas (i.e., gas that is free of CO2) during inspiration in patients receiving invasive mechanical ventilation. By clearing the CO2 that normally remains in the upper airway after exhalation (anatomical dead space), TF can dramatically reduce anatomical dead space without the need to increase the delivered VT. Reducing dead space offers a theoretical benefit in mitigating the mechanisms of lung and diaphragm injury during spontaneous breathing by reducing the ventilation demands to the lungs. Animal studies using the TF have shown extremely promising results, however, the impact of reducing anatomical dead space using the TF on gas exchange, ventilation, and respiratory drive in critically ill patients with AHRF is unknown.

Throughflow is a novel system that reduces anatomical dead space by providing a constant flow of fresh gas (i.e., gas that is free of CO2) during inspiration in patients receiving invasive mechanical ventilation. By clearing the CO2 that normally remains in the upper airway after exhalation (anatomical dead space), TF can dramatically reduce anatomical dead space without the need to increase the delivered VT, making it a safe strategy in terms of lung protection. This reduction in dead space reduces the ventilatory demands of the patients, reducing respiratory drive.

Ventilation with Throughflow will be started at a duty cycle of 20% (TF titration 20%). After 10 minutes measurements will be collected. If Edi is above 5 µV, TF duty cycle will be increased by 20% (TF 40%). Measurements will be collected again after 10 minutes. TF duty cycle will be increased by 10% (TF duty cycle 50% and so on) and measurements collected every 10 minutes until Edi is below 5 µV or TF duty cycle reaches 100%. Once the Edi target has been met, sedation will be progressively reduced to evaluate the effect of Throughflow on sedation requirements for controlling respiratory effort.

Changes in esophageal pressure swing from baseline to protocol completion will be described using central tendency and dispersion measurements (median and 25%-75% interquartile range) for each variable at each time point of the protocol

Changes in the dynamic driving transpulmonary pressure from baseline to protocol completion will be described using central tendency and dispersion measurements (median and 25%-75% interquartile range) for each variable at each time point of the protocol

Changes in PaO2/FiO2 from baseline to protocol completion will be described using central tendency and dispersion measurements (median and 25%-75% interquartile range) for each variable at each time point of the protocol

Changes in sedation achieved during the sedation titration phase and whether maintaining TF can facilitate reductions in sedation based on the effect of withdrawing Throughflow will be assessed

Inclusion Criteria: PaO2/FiO2 less than or equal to 300 at time of screening Oral endotracheal intubation and mechanical ventilation Bilateral airspace opacities on chest radiograph or chest CT scan Exclusion Criteria: Contraindication to esophageal catheterization (upper gastrointestinal tract surgery within preceding 6 weeks, bleeding esophageal/gastric varices) Intubation for traumatic brain injury or stroke Intracranial hypertension (suspected or diagnosed by medical team) Anticipated liberation from mechanical ventilation within 24 hours