Brain Tissue Oxygen and Cerebrovascular Reactivity in Traumatic Brain Injury: A CENTER-TBI Exploratory Analysis of Insult Burden.

Pressure reactivity index (PRx) and brain tissue oxygen (PbtO2) are associated with outcome in TBI. This study explores the relationship between PRx and PbtO2 in adult moderate/severe TBI. Using the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) high resolution ICU sub-study cohort, we evaluated those patients with archived high-frequency digital intra-parenchymal ICP and PbtO2 monitoring data of a minimum of 6 hours in duration, and the presence of a 6 month Glasgow Outcome Scale -Extended (GOSE) score. Digital physiologic signals were processed for ICP, PbtO2 and pressure reactivity index (PRx), with the % time above/below defined thresholds determined. The duration of ICP, PbtO2 and PRx derangements was characterised. Associations with dichotomized 6-month GOSE (alive/dead, and favourable/unfavourable outcome; 4 or less = unfavourable), were assessed. A total of 43 patients were included. Severely impaired cerebrovascular reactivity was seen during elevated ICP and low PbtO2 episodes. However, most of the acute ICU physiologic derangements were impaired cerebrovascular reactivity, not ICP elevations or low PbtO2 episodes. Low PbtO2 without PRx impairment was rarely seen. % time spent above PRx threshold was associated with mortality at 6-months for thresholds of 0 (AUC 0.734, p=0.003), above +0.25 (AUC 0.747, p=0.002) and above +0.35 (AUC 0.745, p=0.002). Similar relationships were not seen for % time with ICP above 20 mmHg, and PbtO2 below 20 mmHg in this cohort. Extreme impairment in cerebrovascular reactivity is seen during concurrent episodes of elevated ICP and low PbtO2. However, the majority of the deranged cerebral physiology seen during the acute ICU phase is impairment in cerebrovascular reactivity, with most impairment occurring in the presence of normal PbtO2 levels. Measures of cerebrovascular reactivity appear to display the most consistent associations with global outcome in TBI, compared to ICP and PbtO2. Keywords: autoregulation, brain tissue oxygen, ICP, physiologic burden.