Pulmonary Gas Transport and Drug Delivery in a Patient Specific Lung Model During Invasive High Frequency Oscillatory Ventilation

Abstract The objective of this dissertation research was to investigate gas transport, mixing and aerosol-drug delivery during high frequency oscillatory ventilation (HFOV) for various ventilator specific conditions that are vital to critical care clinicians. A large eddy simulation based computational fluid dynamics approach was used in a patient specific human lung model to analyze the effect of invasive HFOV on patient management. Different HFOV waveform shapes and frequencies was investigated and the square waveform was found to be most efficient for gas mixing; resulting in the least wall shear stress on the lung epithelium layer thereby reducing the risk of barotrauma to both airways and the alveoli for patients undergoing therapy. Traditional (outlet) boundary conditions based on mass fraction or outlet pressures were found to be inadequate in describing the complex flow physics that occurs during HFOV. Physiological boundary conditions that used the time-dependent pressure coupled with the airways resistance and compliance (R&C) were derived and used for the first time to investigate the lung lobar ventilation and gas exchange for accurate HFOV modeling. A Lagrangian approach was then used to model gas-solid two-phase flow that allowed investigation of the potential of aerosol-drug delivery under HFOV treatment. We report, for the first time, computational fluid dynamics studies to investigate the possibilities of aerosol drug delivery under HFOV. Understanding the role of different carrier gases on the gas exchange and particle deposition, which may allow for optimum drug delivery and ventilation strategy during HFOV. Increasing the operating frequency resulted in a significant change in the global and local deposition indicating strong dependency on the frequency, which could be beneficial for the targeted drug delivery. The global deposition as a fraction of the total injected particles at the endotracheal tube inlet was equivalent to the cases of normal breathing and conventional mechanical ventilation signifying a potential for efficient drug delivery during HFOV. In addition, HFOV had a unique characterization of the local particle deposition due to the rapid ventilation process and a strong influence of the endotracheal tube jet. Very often during ventilation therapy, a clinician uses a cocktail of various gases to enhance targeted therapy. To quantify this process for a futuristic HFOV based patient management, we undertook detailed studies to understand the role of carrier gas properties in gas exchange and particle transport during HFOV. A substantial amplification of the pendelluft flow was achieved by utilizing a low-density carrier gas instead of air, which resulted in gas exchange improvement. Reducing the carrier gas density was found to significantly alter the aerosol-drug delivery under HFOV management. As the density decreased, the deposition fraction in the upper tracheobronchial tree decreased, indicating enhancement of the lung periphery delivery. Furthermore, the filtered aerosol-drug in the ventilator circuit could be significantly reduced by using Heliox, and further reduction could be achieved by reducing the operating frequency. In general, high-frequency oscillatory ventilation therapy could be improved under Heliox with greater content of Helium, thereby reducing the lung hyperinflation risk.