Haghnegahdar Ahmadreza, Zhao Jianan, Kozak Max, Williamson Patrick, Feng Yu
School of Chemical Engineering, Oklahoma State University, Stillwater, OK 74078, USA.
Heliyon. 2019 Apr 10;5(4):e01461. doi: 10.1016/j.heliyon.2019.e01461. eCollection 2019 Apr.
Administering 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 can minimize the impact on the cardiovascular system and provide the neuroprotective effect, hemodynamic stability, and fast recovery. However, the inhalation pattern still needs to be carefully monitored and controlled to avoid health risks caused by over administering xenon to patients during unconsciousness. Thus, high-resolution lung absorption and whole-body translocation data are critically needed to fully understand how to administer the gas 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 in the human body, a realistic breathing waveform and two steady-state flow rates with inhalation durations of 2 and 1.5 seconds were selected. For the realistic breathing cycle, the inhalation-exhalation periods are defined for a human at rest and the other two cases have a fixed volumetric flow rate of 15 L/min. As the two latter cases only simulate the inspiratory phase, a 1-second holding time was applied to represent the missing periods of the full breathing time. Simulations were performed in a subject-specific human upper airway configuration from mouth to G6. Numerical results show that with the accurate lung uptake predictions obtained from the CFD model, the hybrid CFD-PBPK model with TRANSIT compartments generates more precise and breath-specific trends compared to simple PBPK models. Numerical results demonstrate that 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. Furthermore, parametric analyses were performed for the influence of breathing patterns on local airflow distributions, gas species translocations, and lung elimination mechanisms followed by species diffusion into the systemic regions.
通过肺部途径给予不正确剂量的传统麻醉剂可能会导致潜在的健康风险，如血液凝固、血小板功能障碍和器官功能恶化。作为一种替代方法，氙气可以将对心血管系统的影响降至最低，并提供神经保护作用、血流动力学稳定性和快速恢复。然而，吸入模式仍需仔细监测和控制，以避免在患者无意识期间过量给予氙气而导致健康风险。因此，迫切需要高分辨率的肺部吸收和全身转运数据，以充分了解如何给予这种气体并与患者协调以准确控制剂量。由于临床研究的操作灵活性和成像分辨率有限，无法提供准确的剂量测定数据。因此，本研究采用计算流体动力学（CFD）模型来模拟吸入氙气的传输和吸收，并将其与基于生理的药代动力学（PBPK）模型相结合，以预测其向全身区域的转运。为了研究不同呼吸模式对人体中氙气传输动力学的影响，选择了一个真实的呼吸波形以及两种稳态流速，吸入持续时间分别为2秒和1.5秒。对于真实的呼吸周期，定义了人体休息时的吸气-呼气周期，另外两种情况的固定体积流速为15升/分钟。由于后两种情况仅模拟吸气阶段，因此应用1秒的保持时间来代表完整呼吸时间中缺失的阶段。在从口腔到G6的特定个体的人体上呼吸道构型中进行了模拟。数值结果表明，通过CFD模型获得准确的肺部摄取预测，与简单的PBPK模型相比，具有TRANSIT隔室的混合CFD-PBPK模型产生更精确且特定于呼吸的趋势。数值结果表明，呼吸模式可显著影响人体对氙气的摄取，这可作为临床医生进行协调以实现优化氙气剂量的关键因素。此外，还对呼吸模式对局部气流分布、气体物种转运以及随后物种扩散到全身区域的肺部清除机制的影响进行了参数分析。
