Impact of Age and Biological Sex on Cerebrovascular Reactivity in Adult Moderate/Severe Traumatic Brain Injury: An Exploratory Analysis

Abstract

Age and biological sex are two potential important modifiers of cerebrovascular reactivity post-traumatic brain injury (TBI) requiring close evaluation for potential subgroup responses. The goal of this study was to provide a preliminary exploratory analysis of the impact of age and biological sex on measures of cerebrovascular function in moderate/severe TBI. Forty-nine patients from the prospectively maintained TBI database at the University of Manitoba with archived high-frequency digital cerebral physiology were evaluated. Cerebrovascular reactivity indices were derived as follows: PRx (correlation between intracranial pressure [ICP] and mean arterial pressure [MAP]), PAx (correlation between pulse amplitude of ICP [AMP] and MAP), and RAC (correlation between AMP and cerebral perfusion pressure [CPP]). Time above clinically significant thresholds for each index was calculated over different periods of the acute intensive care unit stay. The association between PRx, PAx, and RAC measures with age was assessed using linear regression, and an age trichotomization scheme (<40, 40–60, >60) using Kruskal-Wallis testing. Similarly, association with biological sex was tested using Mann-Whitney U testing. Biological sex did not demonstrate an impact on any measures of cerebrovascular reactivity. Linear regression between age and PAx and RAC demonstrated a statistically significant positive linear relationship. Median PAx and RAC measures between trichotomized age categories demonstrated statistically significant increases with advancing age. The PRx failed to demonstrate any statistically significant relationship with age in this cohort, suggesting that in elderly patients with controlled ICP, PAx and RAC may be better metrics for detecting impaired cerebrovascular reactivity. Biological sex appears to not be associated with differences in cerebrovascular reactivity in this cohort. The PRx performed the worst in detecting impaired cerebrovascular reactivity in those with advanced age, where PAx and RAC appear to have excelled. Future work is required to validate these findings and explore the utility of different cerebrovascular reactivity indices.

Impact of Chronological Age and Biological Sex on Cerebrovascular Reactivity in Moderate/Severe Traumatic Brain Injury: A CAnadian High-Resolution Traumatic Brain Injury (CAHR-TBI) Study

“…In an attempt to remedy this, the Winnipeg Acute TBI Laboratories performed an exploratory analysis that showed that there was a statistically significant relationship between PAx, RAC and age with linear regression and age trichotomization analysis but not with PRx and age. 16 Also, in their cohort, biological sex did not have an impact on the cerebrovascular reactivity measures. 16 This cohort had well controlled ICP and CPP values over the course of their intensive care unit (ICU) stay.…”

“…16 Also, in their cohort, biological sex did not have an impact on the cerebrovascular reactivity measures. 16 This cohort had well controlled ICP and CPP values over the course of their intensive care unit (ICU) stay. Subsequently, such findings suggested that AMP-based cerebrovascular reactivity indices performed superior to the standard PRx in detecting impaired reactivity in populations with advancing age.…”

“…9,[13][14][15] PRx is most widely published on, while PAx and RAC continue to emerge in the literature with very promising results. 9,[15][16][17][18][19] However, regardless of the measure utilized, our understanding of the drivers and modulators of impaired cerebrovascular reactivity after moderate/ severe TBI remains largely unclear. 2,[20][21][22][23][24] Two important potential modifiers of cerebrovascular and secondary injury responses are chronological age and biological sex.…”

“…Age is one of the major drivers of prognosis and is a crucial component of existing standard prognostic models in moderate/severe TBI. 16 Elderly persons tend to suffer poor outcomes after sustaining a TBI as arterial integrity and functions deteriorate in most cases secondary to deleterious effects of chronic illnesses, poor neuronal repair mechanisms and deposits of biological matter in the arterial walls. [25][26][27][28] Next, biological sex impacts cerebrovas-cular response in TBI independently and even in relation to advancing age.…”

Dynamic structures and emerging trends in the management of major trauma: A bibliometric analysis of publications between 2012 and 2021

“…In cluster #0, the literature largely reported on the management of severe traumatic brain injury (42)(43)(44)(45)(46)(47). The management of traumatic brain injury (TBI) has changed over the past decade; a multimodal approach is now being applied in detecting and treating the pathophysiological derangements.…”