Background

Both intracranial pressure (ICP) and the cerebrovascular pressure reactivity represent the dysregulation of pathways directly involved in traumatic brain injury (TBI) pathogenesis and have been used to inform clinical management. However, how these parameters evolve over time following injury and whether this evolution has any prognostic importance have not been studied.

Methods and findings

We analysed the temporal profile of ICP and pressure reactivity index (PRx), examined their relation to TBI-specific mortality, and determined if the prognostic relevance of these parameters was affected by their temporal profile using mixed models for repeated measures of ICP and PRx for the first 240 hours from the time of injury. A total of 601 adults with TBI, admitted between September 2002 to January 2016, and with high-resolution continuous monitoring from a single centre, were studied. At 6 months postinjury, 133 (19%) patients had a fatal outcome; of those, 88 (78%) died from nonsurvivable TBI or brain death. The difference in mean ICP between those with a fatal outcome and functional survivors was only significant for the first 168 hours after injury (all p < 0.05). For PRx, those patients with a fatal outcome also had a higher (more impaired) PRx throughout the first 120 hours after injury (all p < 0.05). The separation of ICP and PRx was greatest in the first 72 hours after injury. Mixed models demonstrated that the explanatory power of the PRx decreases over time; therefore, the prognostic weight assigned to PRx should similarly decrease. However, the ability of ICP to predict a fatal outcome remained relatively stable over time. As control of ICP is the central purpose of TBI management, it is likely that some of the information that is reflected in the natural history of ICP changes is no longer apparent because of therapeutic intervention.

Conclusions

We demonstrated the temporal evolution of ICP and PRx and their relationship with fatal outcome, indicating a potential early prognostic and therapeutic window. The combination of dynamic monitoring variables and their time profile improved prediction of outcome. Therefore, time-driven dynamic modelling of outcome in patients with severe TBI may allow for more accurate and clinically useful prediction models. Further research is needed to confirm and expand on these findings.

中文翻译：

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严重创伤性脑损伤中颅内压和脑血管反应性的时间变化及其与致命结局的关系：一项观察性研究

背景

颅内压（ICP）和脑血管压反应性都代表直接参与创伤性脑损伤（TBI）发病机理的通路失调，已被用于临床管理。但是，尚未研究这些参数在受伤后如何随时间变化以及这种变化是否具有任何预后重要性。

方法和发现

我们分析了ICP和压力反应指数（PRx）的时间变化，检查了它们与TBI特异性死亡率的关系，并使用混合模型对ICP和PRx进行了重复测量，确定了这些参数的预后相关性是否受其时间变化影响。从受伤后的头240小时开始。研究对象为2002年9月至2016年1月之间入院的601例TBI成人，并从单个中心进行了高分辨率的连续监测。受伤后6个月，有133名（19％）患者有致命的预后。其中88（78％）因无法生存的TBI或脑部死亡而死亡。具有致命结果的患者与功能幸存者之间的平均ICP差异仅在受伤后的前168小时才显着（所有p<0.05）。对于PRx，那些具有致命结果的患者在受伤后的前120个小时内PRx也更高（更受损）（所有p <0.05）。受伤后的头72小时内ICP和PRx的分离最大。混合模型表明PRx的解释能力会随着时间的推移而降低；因此，分配给PRx的预后权重应同样减少。但是，随着时间的流逝，ICP预测致命结果的能力仍然相对稳定。由于ICP的控制是TBI管理的主要目的，由于治疗干预，ICP的自然史中反映的某些信息可能不再明显。

结论

我们证明了ICP和PRx的时间演变及其与致命结局的关系，表明了潜在的早期预后和治疗窗口。动态监视变量及其时间配置文件的结合改善了对结果的预测。因此，时间驱动的重型TBI患者预后动态建模可以提供更准确和临床上有用的预测模型。需要进一步的研究来确认和扩大这些发现。