Donald Rob, Howells Tim, Piper Ian, Enblad P, Nilsson P, Chambers I, Gregson B, Citerio G, Kiening K, Neumann J, Ragauskas A, Sahuquillo J, Sinnott R, Stell A
Stats Research Ltd, Dingwall, Scotland, UK.
Department of Neurosurgery, Uppsala University Hospital, Uppsala, Sweden.
J Clin Monit Comput. 2019 Feb;33(1):39-51. doi: 10.1007/s10877-018-0139-y. Epub 2018 May 24.
Traumatically brain injured (TBI) patients are at risk from secondary insults. Arterial hypotension, critically low blood pressure, is one of the most dangerous secondary insults and is related to poor outcome in patients. The overall aim of this study was to get proof of the concept that advanced statistical techniques (machine learning) are methods that are able to provide early warning of impending hypotensive events before they occur during neuro-critical care. A Bayesian artificial neural network (BANN) model predicting episodes of hypotension was developed using data from 104 patients selected from the BrainIT multi-center database. Arterial hypotension events were recorded and defined using the Edinburgh University Secondary Insult Grades (EUSIG) physiological adverse event scoring system. The BANN was trained on a random selection of 50% of the available patients (n = 52) and validated on the remaining cohort. A multi-center prospective pilot study (Phase 1, n = 30) was then conducted with the system running live in the clinical environment, followed by a second validation pilot study (Phase 2, n = 49). From these prospectively collected data, a final evaluation study was done on 69 of these patients with 10 patients excluded from the Phase 2 study because of insufficient or invalid data. Each data collection phase was a prospective non-interventional observational study conducted in a live clinical setting to test the data collection systems and the model performance. No prediction information was available to the clinical teams during a patient's stay in the ICU. The final cohort (n = 69), using a decision threshold of 0.4, and including false positive checks, gave a sensitivity of 39.3% (95% CI 32.9-46.1) and a specificity of 91.5% (95% CI 89.0-93.7). Using a decision threshold of 0.3, and false positive correction, gave a sensitivity of 46.6% (95% CI 40.1-53.2) and specificity of 85.6% (95% CI 82.3-88.8). With a decision threshold of 0.3, > 15 min warning of patient instability can be achieved. We have shown, using advanced machine learning techniques running in a live neuro-critical care environment, that it would be possible to give neurointensive teams early warning of potential hypotensive events before they emerge, allowing closer monitoring and earlier clinical assessment in an attempt to prevent the onset of hypotension. The multi-centre clinical infrastructure developed to support the clinical studies provides a solid base for further collaborative research on data quality, false positive correction and the display of early warning data in a clinical setting.
创伤性脑损伤(TBI)患者面临继发性损伤的风险。动脉低血压,即严重的低血压,是最危险的继发性损伤之一,与患者的不良预后相关。本研究的总体目标是证明先进的统计技术(机器学习)能够在神经重症监护期间即将发生的低血压事件发生之前提供预警。利用从BrainIT多中心数据库中选取的104例患者的数据,开发了一种预测低血压发作的贝叶斯人工神经网络(BANN)模型。使用爱丁堡大学继发性损伤分级(EUSIG)生理不良事件评分系统记录和定义动脉低血压事件。BANN在随机选择的50%的可用患者(n = 52)上进行训练,并在其余队列中进行验证。然后进行了一项多中心前瞻性试点研究(第1阶段,n = 30),该系统在临床环境中实时运行,随后进行了第二项验证性试点研究(第2阶段,n = 49)。根据这些前瞻性收集的数据,对其中69例患者进行了最终评估研究,有10例患者因数据不足或无效而被排除在第2阶段研究之外。每个数据收集阶段都是在实际临床环境中进行的前瞻性非干预性观察研究,以测试数据收集系统和模型性能。在患者入住重症监护病房期间,临床团队无法获得预测信息。最终队列(n = 69)使用0.4的决策阈值,并包括假阳性检查,灵敏度为39.3%(95%CI 32.9 - 46.1),特异度为91.5%(95%CI 89.0 - 93.7)。使用0.3的决策阈值并进行假阳性校正,灵敏度为46.6%(95%CI 40.1 - 53.2),特异度为85.6%(95%CI 82.3 - 88.8)。使用0.3的决策阈值,可以实现对患者不稳定情况超过15分钟的预警。我们已经证明,在实际的神经重症监护环境中使用先进的机器学习技术,可以在潜在的低血压事件出现之前为神经重症团队提供早期预警,从而进行更密切的监测和更早的临床评估,以试图预防低血压的发生。为支持临床研究而开发的多中心临床基础设施为进一步开展关于数据质量、假阳性校正以及在临床环境中显示早期预警数据方面的合作研究提供了坚实的基础。