Preclinical Evaluation of Multifrequency Oscillatory Ventilation in a Large-Animal Model of Acute Respiratory Failure
Abstract
Respiratory failure from acute lung injury, now termed acute respiratory distress syndrome (ARDS), accounts for 4 million days annually in the intensive care units throughout the United States, and is associated with a high death rate in civilians and military personnel -- up to 40% patients diagnosed with ARDS will die within a 28-day period. Moreover, survivors of ARDS may have substantial long-term problems due to physical and mental health impairments. Military personnel in combat environments are at particular risk for developing ARDS due to viral pandemics, trauma, inhalation injury, and exposure to chemical, biological, or nuclear weapons. ARDS thus imposes significant burdens on military and public health resources worldwide, and only minimal improvements in patient survival have occurred over recent decades. A key feature of the lung in ARDS is that different regions of an injured lung can have different mechanical properties, such as how easily it expands or collapses during breathing or ventilation. Thus, many patients with ARDS must be supported on breathing machines, or ventilators, that provide assistance by using positive airway pressure. Lung protective ventilation strategies use high average airway pressures but small breathing volumes in order to keep the lung inflated while minimizing the amount that it may be stretched. Such strategies have significantly improved survival in patients with ARDS, although the death rate remains high. This is because the best ventilator settings for one lung region may not necessarily be the same for another, even within the same patient: some areas become overinflated and damaged, while other areas may be underinflated and collapse. This detrimental process is referred to as “ventilator-induced lung injury” (VILI), and may cause the lung to release different inflammatory mediators that not only worsen existing lung injury, but may also lead to additional organ failure and death. The goal of our previous PRMRP research project was to develop a novel method for mechanical ventilation, called “Multi-Frequency Oscillatory Ventilation” (MFOV) that optimized the delivery of oxygen and removal of carbon dioxide from the lung (gas exchange), while simultaneously preserving lung protective ventilation. In a sense, MFOV allows each part of the lung to act as a unique “mechanical filter,” and use whatever component of the multi-frequency waveform it is best suited for. With our previous award, we demonstrated that short-term application of MFOV in small pigs with ARDS provided more efficient gas exchange compared to traditional forms of mechanical ventilation, and improved mechanical lung function as well. For the next phase of our work, we will demonstrate that MFOV, delivered with a prototype adult human oscillator, is capable of maintaining superior lung protective ventilation in a preclinical, large animal model of ARDS. We hypothesize that application of MFOV in animals with adult, human-sized lungs will be associated with lower risk for VILI, compared to traditional forms of mechanical ventilation that are currently used in military and civilian clinical environments. In Specific Aim 1, we will demonstrate that MFOV is associated with less injurious ventilation when applied over longer durations (12 hours), based on measures of inflammation in the blood and airspaces of the lung. In Specific Aim 2, we will use dynamic computed tomographic (CT) imaging to establish that enhanced aeration and reduced stretch in the lung tissues are the mechanisms by which MFOV improves mechanical function and reduces inflammation. Ultimately, this innovative combination of physiologic experiments and CT imaging will yield a new mode of ventilation that is better specifically “tuned” to the heterogeneous mechanics of the lung with ARDS in both military and civilian settings. MFOV thus has potential to change the current treatment strategies and protocols for critically ill ventilated patients
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 05, 2021
- Source ID
- W81XWH2110507
Entities
People
- David W. Kaczka
Organizations
- United States Army
- University of Iowa