Diffuse Intracranial Injury Patterns Are Associated with Impaired Cerebrovascular Reactivity in Adult Traumatic Brain Injury: A CENTER-TBI Validation Study

Abstract

Recent single center retrospective analysis displayed the association between admission computed tomography (CT) markers of diffuse intra-cranial (IC) injury and worse cerebrovascular reactivity. The goal of this study is to further explore these associations using the prospective multi-center Collaborative European Neurotrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) high resolution data set (HR ICU). Using the CENTER-TBI HR ICU sub-study cohort, we evaluated those patients with both archived high-frequency digital physiology (100 Hz or higher), and the presence of a digital admission CT scan. Physiologic signals were processed for pressure reactivity index (PRx) and both the % time above defined PRx thresholds and mean hourly dose above threshold. Admission CT injury scores were obtained from the database. Quantitative contusion, edema, intraventricular hemorrhage (IVH) and extra-axial lesion volumes were obtained via semi-automated segmentation. Comparison between admission CT characteristics and PRx metrics was conducted using Mann-U, Jonckheere Terpstra testing, with a combination of univariate linear and logistic regression techniques. A total of 165 patients were included. Cisternal compression and high admission Rotterdam and Helsinki CT scores, and Marshall CT diffuse injury sub-scores were associated with increased % time and hourly dose above PRx threshold of 0, +0.25 and +0.35 (p<0.02 for all).Logistic regression analysis displayed an association between deep peri-contusional edema and mean PRx above threshold of +0.25. These results suggest that diffuse injury patterns, consistent with acceleration/deceleration forces, are associated with impaired cerebrovascular reactivity. Diffuse admission IC injury patterns appear to be consistently associated with impaired cerebrovascular reactivity, as measured through PRx. This is in keeping with the previous single center retrospective literature on the topic. This study provides multicenter validation for those results, and provide preliminary data to support potential risk stratification for impaired cerebrovascular reactivity based on injury pattern.

Systemic Markers of Injury and Injury Response Are Not Associated with Impaired Cerebrovascular Reactivity in Adult Traumatic Brain Injury: A Collaborative European Neurotrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) Study

“…More detailed information on this population's admission CT characteristics can be found in our previous manuscript evaluating the association between admission intra-cranial injury burden and impaired cerebrovascular reactivity. 18,26 * Table 2 here…”

“…16 We have some literature to support the association between diffuse intra-cranial injury patterns and impaired cerebrovascular reactivity, 17 with recent multi-center evidence supporting these findings. 18 Further, some preliminary literature supports the association between impaired reactivity and the presence of cortical spreading depression. 19,20 This small number of studies is the extent of our current knowledge of what drives impaired reactivity in TBI.…”

“…We required the admission CT scans so that we could adjust for the known admission intra-cranial CT characteristics associated with impaired cerebrovascular reactivity, as defined by our recently published work from this cohort. 18 Patients with EVD based ICP data were excluded given the interrupted nature of their recordings (i.e. reliable ICP can be recorded only when the drainage is closed).…”

“…Further semi-automated segmentation of the admission CT scans was conducted as described in Appendix A of the Supplementary materials, as part of a separate CENTER-TBI study on the association between admission CT characteristics and cerebrovascular reactivity. 18,26 Only the CT variables found to be statistically associated with impaired cerebrovascular reactivity from this previous study were extracted for this project, allowing us to adjust for known associated intra-cranial injury characteristics.…”

“…These CT characteristics include: Helsinki CT grade, deep contusion edema volume (consisting of basal ganglia, brainstem and cerebellar locations), extra-axial lesion volume and presence of basal cistern compression. 18 CENTER-TBI data version 2.0 was accessed for the purpose of this study, via Opal database software. 27 Finally, we collected admission extra-cranial markers of injury burden and potential host systemic injury response.…”