Using Patient Simulation to Optimize Hospital Insulin Infusion in Cardiac Surgery

项目摘要/摘要 应激性高血糖和相关的血糖变异性在重症监护中很常见，并已被发现 导致感染、伤口愈合缓慢以及短期和长期死亡率。早期临床试验 在手术患者中使用强化胰岛素治疗维持严格的血糖控制(TGC)，导致 住院死亡率下降34%，发病率也相应下降。因此，许多人 医院为他们的重症监护病房(ICU)患者采用了积极的住院血糖目标。 然而，在随后的研究中，TGC的好处不那么明显。许多因素导致了 报告的TGC结果的变异性，包括(I)胰岛素治疗方案本身，它提供了 在类似情况下，胰岛素剂量推荐出人意料地不同：(Ii) 不同患者人群中的极端血糖变异性，以及(Iii)评估方法的准确性 血糖浓度，并告知胰岛素治疗。开发优化胰岛素的主要障碍 治疗方案是临床试验既昂贵又耗时，而且不能与血糖水平相比 相同患者中不同方案的结果。为了克服这些问题，我们已经提出并 基于(I)的创新生物工程胰岛素治疗设计方法(BITDM)的部分验证 井中患者胰岛素敏感性参数的群体特异性变异性特征 验证的葡萄糖代谢模拟模型；(Ii)建立基于计算机的ICU血糖模拟器 以虚拟受试者群体为中心，复制真实患者群体的反应 不同的胰岛素疗法；以及(Iii)基于模拟器的TGC算法的计算机设计和优化。 这一提议的中心假设是BITDM可以提供一种准确的评估手段， 比较和优化胰岛素方案，在特定的患者群体中安全地改善TGC 这是心血管手术(CVS)患者的例子。据此，提出了以下具体目标： 目的1.将BITDM应用于脑血管痉挛术后患者的不同生理状态。 目的2.建立基于BITDM的胰岛素方案优化在S大学的有效性。 心胸重症监护室。 一旦建立，BITDM将允许测试、比较不同的血糖管理策略 并在一组常见的硅胶患者中进行优化，其成本和时间仅为 进行临床试验。如果成功，这项研究将使我们能够开始解决我们的长期目标- 开发一种基于模拟器的生物工程方法来优化安全的胰岛素治疗 实现TGC，并允许改善结果。

Project Summary / Abstract Stress hyperglycemia and associated glycemic variability are common in critical care and have been found to contribute to infection, slow wound healing, and short and long-term mortality. Early clinical trials utilizing intensive insulin therapy to maintain Tight Glycemic Control (TGC) in surgical patients, resulted in a 34% decrease in in-hospital mortality and comparable decreases in morbidity. Consequently, many hospitals adopted aggressive inpatient glycemic targets for their Intensive Care Unit (ICU) patients. However, in subsequent studies the benefits of TGC were less apparent. Many factors contribute to the variability of reported TGC outcomes, including (i) the insulin therapy protocols themselves, which offer surprisingly divergent insulin dose recommendations under similar circumstances, (ii) the etiology of extreme BG variability in diverse patient populations, and (iii) the accuracy of the methods used to assess BG concentration and inform the insulin therapies. The main obstacle to developing optimized insulin therapy protocols is that clinical trials are expensive, time consuming, and cannot compare glycemic outcomes for different protocols in identical patients. To overcome these problems we have proposed and partially validated an innovative Bioengineering Insulin Therapy Design Methodology (BITDM) based on (i) characterization of the population-specific variability in patients' insulin sensitivity parameters in a well validated simulation model of glucose metabolism; (ii) creation of a computer-based ICU BG Simulator centered around a virtual subject population that replicates the responses of the real patient population to different insulin therapies; and (iii) simulator-based in silico design and optimization of TGC algorithms. The central hypothesis of this proposal is that BITDM can provide an accurate means of evaluating, comparing, and optimizing insulin protocols that safely improves TGC in specific patient populations, in this instance cardiovascular surgery (CVS) patients. Accordingly, the following specific aims are proposed: Aim 1. Apply BITDM to the distinct physiology of postoperative CVS patients. Aim 2. Establish the efficacy of BITDM-based insulin protocol optimization within U.Va.'s cardiothoracic ICU. Once established, BITDM will allow for different glycemic management strategies to be tested, compared and optimized within a common set of in silico patients at a fraction of the cost and time it will take to perform a clinical trial. If successful, this study will allow us to start addressing our long-term goal - developing a simulator-based bioengineering methodology for optimization of insulin treatment that safely achieves TGC and allows for improved outcomes.