Visualizations of Autoregulatory Insults in Traumatic Brain Injury: A Collaborative European NeuroTrauma Effectiveness Research-Traumatic Brain Injury Cohort Study

Cerebral blood flow disturbances, including ischemia and hyperemia, due to impaired cerebral autoregulation (CA), are common and unfavorable in traumatic brain injury (TBI). The pressure reactivity index (PRx) reflects CA status and is associated with patient outcomes. Yet, the impact of the combined intensity and duration of CA insults and the temporal evolution of CA impairment in relation to outcome remains unclear. Moreover, how PRx modulates safe and dangerous thresholds for intracranial pressure (ICP), cerebral perfusion pressure (CPP), and CPP deviation from optimal CPP (ΔCPPopt) is not well defined. This study aimed to clarify these relationships using granular outcome heatmaps. In this prospective, observational, cohort within the Collaborative European NeuroTrauma Effectiveness Research in TBI (CENTER-TBI), 166 patients with TBI, admitted between 2014 and 2017 from 21 recruiting centers, were included. Demography, admission status, and clinical outcome were evaluated. A favorable outcome was defined as Extended Glasgow Outcome Scale (GOSE) 5–8 at 6 months post-injury. High-frequency data of ICP, CPP, PRx, and ΔCPPopt during the first 7 days of neurocritical care were analyzed and visualized in color-coded heatmaps. PRx >0.30 and negative ΔCPPopt were strongly associated with unfavorable outcomes, particularly when sustained for longer durations. The physiological ranges associated with a favorable outcome for PRx and ΔCPPopt remained stable over the first 7 days post-injury. PRx modulated the safe and dangerous intervals of the other cerebral physiological variable, as the combination of high PRx together with high ICP, low CPP, and negative ΔCPPopt, respectively, was particularly associated with worse outcomes. Moreover, the unfavorable effect of negative ΔCPPopt primarily occurred when combined with PRx >0.00 rather than for negative ΔCPPopt (mmHg) in general. PRx may be used to fine-tune safe ICP, CPP, and ΔCPPopt targets, particularly in defining the lower limit of CA. Future studies should focus on evaluating the PRx/CPP curve location and steepness rather than mainly focusing on mmHg-deviation from CPPopt or any specific target.