Innovative Method for Real-time Assessment of Intracranial Compliance

严重创伤性脑损伤（TBI）患者的“标准护理”神经监测-领先的 导致儿童和成人死亡和长期神经损伤的原因-几十年来没有改变， 主要依靠颅内压（ICP）监测。值得注意的是，单独使用ICP作为治疗药物， 由于缺乏强有力支持证据，特别是其使用，严重TBI的靶点目前存在争议 小儿 为了满足这一临床需求，我们开发了ICP-PC 02依从性指数（ICP-PCI）， 为了通过整合连续ICP和潮气末CO来实时计算动态颅内顺应性， （ETC 02）数据流。颅内顺应性的床旁评估： 由于缺乏床旁监护，ICP和颅内体积的伴随变化受到限制 测量脑血流量（CBF）/脑血容量（CBV）的设备。ICP-PCI基于众所周知的 血液中CO2分压（PC 02）和CBV之间的关系非常稳定， 在PC 02中，1 mmHg的压力引起严重TBI患者CBF的-3%变化。由于CBF与 血管半径的四次方，CBF的变化反映了CBV的即时变化。作为连续ICP 和ETC 02监测是严重TBI患者的标准护理，ICP-PCI可以使用 现有ICU监护。到目前为止，我们已经获得了IRB中严重TBI儿童的初步数据。 经批准的研究，该研究确认了生理前提并证明了测量ICPPCI的可行性 使用现有的、持续的ICU监测，认为是基于指南的护理标准。在这一提议中， 密集的时间序列数据，包括连续的ETC 02、ICP和其他生理波形， 审问。ICP-PCI将计算为ETC 02和 跨优化的时间时期的ICP，并且经受额外的信号处理。我们将确认我们的 在更大的队列中的研究结果，并定义了ICP-PCI的时间模式和与相关 临床变量：ICP、CPP、ICP监测持续时间、内科和外科干预以及ICU和 住院时间。此外，高密度的时间序列数据将与 电子健康记录（EHR）数据和模拟模型将被生成和完善，以确定能力 ICP-PCI预测相关医疗和手术干预的需求和反应。临床 ICP-PCI的应用将与单独的ICP进行头对头比较。成功验证ICP-PCI 将为开发一个有价值的临床工具奠定基础， 儿童和可能的成人严重创伤性脑损伤，可以很容易地整合和实施，使用 现有ICU监护。

"Standard of care" neurological monitoring for patients with severe traumatic brain injury (TBI) - a leading cause of death and long-term neurological impairment in children and adults-has not changed in decades, relying mainly on intracranial pressure {ICP) monitoring. Remarkably, the use of ICP alone as a therapeutic target for severe TBI is currently controversial due to a lack of robust supporting evidence, especially for its use in children. To address this clinical need, we developed the ICP-PC02 Compliance Index (ICP-PCI), an algorithm to compute dynamic intracranial compliance in real-time by integrating continuous ICP and end tidal CO, (ETC02) data streams. Bedside assessment of intracranial compliance-the relationship between changes in ICP and concomitant changes in intracranial volume, has been limited because of the lack of point-of-care devices to measure cerebral blood flow (CBF)/cerebral blood volume (CBV). The ICP-PCI is based on the well-known and robust relationship between the partial pressure of CO2 in blood (PC02) and CBV, where a change in PC02 of 1 mmHg induces an -3% change in CBF in patients with severe TBI. Since CBF is proportional to blood vessel radius to the fourth power, changes in CBF reflect immediate changes in CBV. As continuous ICP and ETC02 monitoring are standard of care for patients with severe TBI, ICP-PCI can be determined using existing ICU monitoring. To date we have obtained preliminary data in children with severe TBI in an IRB approved study that validates the physiologic premise and demonstrates feasibility for measurement of ICPPCI using existing, continuous ICU monitoring deemed guidelines-based standard of care. In this proposal, dense time series data, including continuous ETC02, ICP, and other physiologic waveforms will be interrogated. ICP-PCI will be calculated as the running moment-to-moment correlation between ETC02 and ICP across optimized temporal epochs, and subject to additional signal processing. We will confirm our findings across a larger cohort and define the temporal pattern of ICP-PCI and associations with relevant clinical variables: ICP, CPP, duration of ICP monitoring, medical and surgical interventions, and ICU and hospital length of stay. In addition, high-density, time series data will be integrated and time-synchronized with electronic health record (EHR) data and simulation models will be generated and refined to define the capacity for ICP-PCI to predict the need and response to relevant medical and surgical interventions. Clinical application of ICP-PCI will be compared head-to-head with ICP alone. Successful validation of ICP-PCI would lay the groundwork for the development of a valuable clinical tool for all Centers managing children and possibly adults with severe TBI, that could be readily integrated and implemented using existing ICU monitoring.