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.

Study Overview

• Status: Recruiting
• Conditions: Respiratory Insufficiency; Lung Injury; Diaphragm Injury
• Intervention / Treatment: Device: Throughflow titration phase

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 15
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Rongyu ( Cindy) Jin; Phone Number: 7613 4163404800; Email: rongyu.jin@uhn.ca

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 2N2
      • Recruiting
      • University Health Network
      • Contact: Cindy Jin; Email: rongyu.jin@uhn.ca

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• PaO2/FiO2 less than or equal to 300 at time of screening
• Oral endotracheal intubation with ETT 7.5 or 8.0 and on invasive 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Throughflow; 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.

Device: Throughflow titration phase; Ventilation will be applied in the TF mode with TF set to 0 LPM for 10 minutes. Patients will receive assist through the NAVA line of the tri-piece (NAVA set to similar settings as Servo period, ~60-80 LPM flow). Ventilation with Throughflow will be started at a TF flow of 5 LPM, and the NAVA flow will be reduced by 5 LPM. After 10 minutes measurements will be collected. If Edi is greater than or equal to 4 µV, TF flow will be increased to 10 LPM and NAVA flow will be adjusted to keep total flow constant. Measurements will be collected again after 10 minutes. TF flow will be increased in steps of 5 LPM and measurements collected every 10 minutes until Edi is below 3 µV or TF flow reaches the total flow observed during the NAVA period. After either the Edi target has been met or TF flow has reached the total flow, ventilation with TF will be reduced in steps of 5 LPM every 10 minutes (the reverse of the above), while NAVA flow is accordingly adjusted to keep total flow constant.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Esophageal pressure swing (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	24 hours
Dynamic driving transpulmonary pressure (lung-distending pressure)	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	24 hours
Oxygenation (PaO2/FiO2 ratio)	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	24 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of serious adverse events	The number of SAEs during the protocol will be measured and quantified.	24 hours

Collaborators and Investigators

• Sponsor: University Health Network, Toronto
• Collaborators: Unity Health Toronto
• Investigators: Principal Investigator: Lorenzo Del Sorbo, University Health Network, Toronto; Principal Investigator: Ewan Goligher, MD, PhD, University Health Network, Toronto

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2024
• Primary Completion (Estimated): June 30, 2025
• Study Completion (Estimated): August 31, 2025

Study Registration Dates

• First Submitted: July 14, 2022
• First Submitted That Met QC Criteria: November 29, 2022
• First Posted (Actual): December 8, 2022

Study Record Updates

• Last Update Posted (Estimated): December 11, 2024
• Last Update Submitted That Met QC Criteria: December 6, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Respiration Disorders; Thoracic Injuries; Respiratory Insufficiency; Wounds and Injuries; Lung Injury
• Other Study ID Numbers: 21-5534

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No