ArabiDarrehDor Ghazal, Kramer George C, Burmeister David M, Salinas Jose, Hahn Jin-Oh
Mechanical Engineering, University of Maryland, College Park, MD, United States.
Anesthesiology, University of Texas Medical Branch, Galveston, TX, United States.
Front Physiol. 2024 Oct 3;15:1467351. doi: 10.3389/fphys.2024.1467351. eCollection 2024.
Treating extensive burn injury requires an individually tailored resuscitation protocol that includes hourly-titrated intravenous fluid infusion to avert both hypovolemic shock and edema. Due to the complexity of burn pathophysiology and significant variability in treatment protocols, there is an ongoing effort to optimize burn resuscitation. The goal of this work is to contribute to this effort by developing a mathematical model of burn pathophysiology and resuscitation for testing of burn resuscitation protocols and decision-support systems.
In our previous work, we developed and validated a mathematical model consisting of volume kinetics, burn-induced perturbations, and kidney function. In this work, we expanded our previous mathematical model to incorporate novel mathematical models of cardiovascular system and hormonal system (renin-angiotensin-aldosterone (RAAS) system and antidiuretic hormone) which affect blood volume and pressure regulation. We also developed a detailed mathematical model of kidney function to regulate blood volume, pressure, and sodium levels, including components for glomerular filtration rate, reabsorption rates in nephron tubules, Tubuglomerular feedback, and myogenic mechanisms. We trained and validated the expanded mathematical model using experimental data from 15 pigs and 9 sheep with extensive burns to quantitatively evaluate its prediction accuracy for hematocrit, cardiac output, mean arterial pressure, central venous pressure, serum sodium levels, and urinary output. We then trained and tested the mathematical model using a clinical dataset of 233 human burn patients with demographic data and urinary output measurements.
The mathematical model could predict all tested variables very well, while internal variables and estimated parameters were consistent with the literature.
To the best of our knowledge, this is the first mathematical model of burn injury and resuscitation which is extensively validated to replicate actual burn patients. Hence, this platform may complement large animal pre-clinical testing of burn resuscitation protocols. Beyond its primary purpose, the mathematical model can be used as a training tool for healthcare providers delivering insight into the pathophysiology of burn shock, and offering novel mathematical models of human physiology which can be independently used for other purposes and contexts.
治疗大面积烧伤需要一个个性化定制的复苏方案，该方案包括按小时滴定的静脉输液，以避免低血容量性休克和水肿。由于烧伤病理生理学的复杂性以及治疗方案的显著变异性，人们一直在努力优化烧伤复苏。这项工作的目标是通过开发一个烧伤病理生理学和复苏的数学模型，为烧伤复苏方案和决策支持系统的测试做出贡献。
在我们之前的工作中，我们开发并验证了一个由容量动力学、烧伤引起的扰动和肾功能组成的数学模型。在这项工作中，我们扩展了之前的数学模型，纳入了影响血容量和血压调节的心血管系统和激素系统（肾素 - 血管紧张素 - 醛固酮（RAAS）系统和抗利尿激素）的新数学模型。我们还开发了一个详细的肾功能数学模型来调节血容量、血压和钠水平，包括肾小球滤过率、肾小管重吸收率、管球反馈和肌源性机制的组成部分。我们使用来自15头猪和9只羊的大面积烧伤实验数据对扩展后的数学模型进行训练和验证，以定量评估其对血细胞比容、心输出量、平均动脉压、中心静脉压、血清钠水平和尿量的预测准确性。然后，我们使用包含人口统计学数据和尿量测量值的233例人类烧伤患者的临床数据集对该数学模型进行训练和测试。
该数学模型能够很好地预测所有测试变量，而内部变量和估计参数与文献一致。
据我们所知，这是第一个经过广泛验证以复制实际烧伤患者情况的烧伤损伤和复苏数学模型。因此，这个平台可以补充烧伤复苏方案的大型动物临床前测试。除了其主要目的外，该数学模型还可以用作医疗保健提供者的培训工具，深入了解烧伤休克的病理生理学，并提供可以独立用于其他目的和背景的人类生理学新数学模型。
