Univariate comparison of performance of different cerebrovascular reactivity indices for outcome association in adult TBI: a CENTER-TBI study.

BACKGROUND: Monitoring cerebrovascular reactivity in adult traumatic brain injury (TBI) has been linked to global patient outcome. Three intra-cranial pressure (ICP)-derived indices have been described. It is unknown which index is superior for outcome association in TBI outside previous single-center evaluations. The goal of this study is to evaluate indices for 6- to 12-month outcome association using uniform data harvested in multiple centers. METHODS: Using the prospectively collected data from the Collaborative European NeuroTrauma Effectiveness Research in TBI (CENTER-TBI) study, the following indices of cerebrovascular reactivity were derived: PRx (correlation between 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)). Univariate logistic regression models were created to assess the association between vascular reactivity indices with global dichotomized outcome at 6 to 12 months, as assessed by Glasgow Outcome Score-Extended (GOSE). Models were compared via area under the receiver operating curve (AUC) and Delong's test. RESULTS: Two separate patient groups from this cohort were assessed: the total population with available data (n = 204) and only those without decompressive craniectomy (n = 159), with identical results. PRx, PAx, and RAC perform similar in outcome association for both dichotomized outcomes, alive/dead and favorable/unfavorable, with RAC trending towards higher AUC values. There were statistically higher mean values for the index, % time above threshold, and hourly dose above threshold for each of PRx, PAx, and RAC in those patients with poor outcomes. CONCLUSIONS: PRx, PAx, and RAC appear similar in their associations with 6- to 12-month outcome in moderate/severe adult TBI, with RAC showing tendency to achieve stronger associations. Further work is required to determine the role for each of these cerebrovascular indices in monitoring of TBI patients.

Comparison of Performance of Different Optimal Cerebral Perfusion Pressure Parameters for Outcome Prediction in Adult Traumatic Brain Injury: A Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) Study.

It has been postulated previously that individualized cerebral perfusion pressure (CPP) targets can be derived from cerebrovascular reactivity indices. Differences between real CPP and target CPP (named generically optimal CPP) has been linked to global outcome in adult traumatic brain injury (TBI). Different vascular reactivity indices can be utilized in the determination. The goal of this study is to evaluate CPPopt parameters, derived from three intracranial pressure (ICP)-derived cerebrovascular reactivity indices, and determine which one is superior for 6- to 12-month outcome prediction. Using the prospectively collected data from the Collaborative European NeuroTrauma Effectiveness Research in TBI (CENTER-TBI) study, the following indices of cerebrovascular reactivity were derived: pressure reactivity index (PRx; correlation between ICP and mean arterial pressure [MAP]), pulse amplitude index (PAx; correlation between pulse amplitude of ICP [AMP] and MAP), and RAC (correlation between AMP and CPP). CPPopt was derived using each index. Univariate logistic regression models were created to assess the association between CPPopt with global dichotomized outcome at 6 to 12 months, as assessed by Glasgow Outcome Score-Extended. Models were compared via area under the receiver operating curve (AUC) and Delong's Test. A total of 204 patients had available data. CPPopt derived from PRx, PAx, and RAC performed variably in their association with outcomes. PRx- and RAC-based CPPopt performed similarly, with RAC parameters trending towards highest AUC values. PAx-based CPPopt parameters failed to reach significant associations with dichotomized outcomes at 6 to 12 months. CPPopt parameters derived from PRx and RAC appear similar in their overall ability for 6- to 12-month outcome prediction in moderate/severe adult TBI.

Validation of Intracranial Pressure-Derived Cerebrovascular Reactivity Indices against the Lower Limit of Autoregulation, Part II: Experimental Model of Arterial Hypotension.

The aim of this work was to explore the relationship between intracranial pressure (ICP)-derived indices of cerebrovascular reactivity and the lower limit of autoregulation (LLA) during arterial hypotension. We retrospectively reviewed recorded physiological data from piglets that underwent controlled hypotension. Hypotension was induced by inflation of a balloon catheter in the inferior vena cava. ICP, cortical laser Doppler flowmetry (LDF), and arterial blood pressure (ABP) monitoring was conducted. ICP-derived indices were calculated: pressure reactivity index (PRx; correlation between ICP and mean arterial pressure [MAP]); pulse amplitude index (PAx; correlation between pulse amplitude of ICP [AMP] and MAP); and RAC (correlation between AMP and cerebral perfusion pressure [CPP]). LLA was estimated by piece-wise linear regression of CPP versus LDF. We produced error bar plots for PRx, PAx, and RAC against 5-mm Hg bins of CPP, displaying the relationship with the LLA. We compared CPP values at clinically relevant thresholds of PRx, PAx, and RAC to CPP measured at the LLA. Receiver operating curve (ROC) analysis was performed for each index across the LLA using 5-mm Hg bins for CPP. Mean LLA was 36.2 ± 10.5 mm Hg. Error bar plots demonstrated that PRx, PAx, and RAC increased, with CPP decreasing below the LLA. CPP at clinically relevant thresholds for PRx, PAx, and RAC displayed weak associations with the LLA, indicating that thresholds defined in TBI may not apply to a model of arterial hypotension. ROC analysis indicated that PRx, PAx, and RAC predicted the LLA, with AUCs of: 0.806 (95% confidence interval [CI], 0.750-0.863; p < 0.0001), 0.726 (95% CI, 0.664-0.789; p < 0.0001), and 0.710 (95% CI, 0.646-0.775; p < 0.0001), respectively. Three ICP-derived continuous indices of cerebrovascular reactivity, PRx, PAx, and RAC, were validated against the LLA within this experimental model of arterial hypotension, with PRx being superior.