10th International Aerosol Conference September 2 - September 7, 2018 America's Center Convention Complex St. Louis, Missouri, USA
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Analysis of Xenon Mass Transfer from Human Upper Airway to Systemic Regions using a Hybrid CFD-PBPK Model
AHMADREZA HAGHNEGAHDAR, Jianan Zhao, Max Kozak, Patrick Williamson, Yu Feng, Oklahoma State University, Stillwater, OK, USA
Abstract Number: 245 Working Group: Aerosols in Medicine
Abstract Administrating incorrect doses of conventional anesthetic agents through the pulmonary route can cause potential health risks such as blood coagulation, platelet dysfunction, and deteriorating organ function. As an alternative, Xenon induces negligible impact on the cardiovascular system and also provide a neuroprotective effect, hemodynamic stability, and fast recovery. However, the inhalation still needs to be carefully monitored and controlled to avoid health risks caused by overdosing patients in unconsciousness. Thus, high-resolution lung absorption and whole-body translocation data are in critical need to fully understand how to administrate the gas via inhalation and coordinate with the patient to accurately control the dose. Clinical studies are not able to provide accurate dosimetry data due to their limited operational flexibility and imaging resolution. Therefore, a Computational Fluid Dynamics (CFD) model was employed in this study to simulate the transport and absorption of the inhaled Xenon which is connected with a Physiologically Based Pharmacokinetic (PBPK) model to predict the translocation into the systemic regions. To study the effects of different breathing patterns on Xenon transport dynamics and the concentration within the plasma and important organs, two inhalation durations (2 sec and 1.5 sec) were selected for each breathing cycle. Averaged inhalation flow rate is fixed at 3L/min to represent adults at rest. As this study only simulate inspiratory phase, a 1-sec holding time was applied to represent the expiratory phase. Simulations were performed in a subject-specific human upper airway configuration from mouth to G6. Our numerical results show that with the accurate lung uptake predictions obtained from the CFD model, the hybrid CFD-PBPK model generates more precise trends compared to simple PBPK models. In both cases, the concentrations increase with time before reaching a plateau after about 20 minutes. For 2-sec and 1.5 sec inhalation durations, the maximum values of Xenon uptake concentration during one single inhalation are approximately 0.1 and 0.07 mol/L respectively. The comparison indicates that higher uptake concentration of Xenon occurs with the long inhalation duration. Furthermore, the parametric analysis indicates that the plasma concentration of Xenon is significantly higher with the long inhalation duration. In conclusion, breathing pattern can significantly influence the Xenon uptake in the human body, which can be utilized as a critical factor to be coordinated by clinicians to achieve the optimized Xenon dose.