Intracranial Pressure-Derived Cerebrovascular Reactivity Indices and Their Critical Thresholds: A Canadian High Resolution-Traumatic Brain Injury Validation Study

Current neurointensive care guidelines recommend intracranial pressure (ICP) and cerebral perfusion pressure (CPP) centered management for moderate-severe traumatic brain injury (TBI) due to their demonstrated associations with patient outcome. Cerebrovascular reactivity metrics, such as the pressure reactivity index (PRx), pulse amplitude index (PAx), and RAC index, have also demonstrated significant prognostic capabilities with regards to outcome. However, critical thresholds for cerebrovascular reactivity indices have only been identified in two studies conducted at the same center. In this study, we aim to determine the critical thresholds of these metrics by leveraging a unique multicenter database. The study included a total of 354 patients from the CAnadian High-Resolution TBI (CAHR-TBI) Research Collaborative. Based on 6-month Glasgow Outcome Scores, patients were dichotomized into Alive vs. Dead and Favorable vs. Unfavorable. Chi-square values were then computed for incrementally increasing values of each physiological parameter of interest against outcome. The values that generated the greatest chi-squares for each parameter were considered to be the thresholds with the greatest outcome discriminatory capacity. To confirm that the identified thresholds provide prognostic utility, univariate and multivariable logistic regression analyses were performed adjusting for the International Mission for Prognosis and Analysis of Clinical Trials (IMPACT) variables. Through the chi-square analysis, a lower limit CPP threshold of 60 mmHg and ICP thresholds of 18 mmHg and 22 mmHg were identified for both survival and favorable outcome predictions. For the cerebrovascular reactivity metrics, different thresholds were identified for the two outcome dichotomizations. For survival prediction, thresholds of 0.35, 0.25, and 0 were identified for PRx, PAx, and RAC, respectively. For favorable outcome prediction, thresholds of 0.325, 0.20, and 0.05 were found. Univariate logistic regression analysis demonstrated that the time spent above/below thresholds were associated with outcome. Further, multivariable logistic regression analysis found that percent time above/below the identified thresholds added additional variance to the IMPACT core model for predicting both survival and favorable outcome. In this study, we were able to validate the results of the previous two works as well as reaffirm the ICP and CPP guidelines from the Brain Trauma Foundation (BTF) and the Seattle International Severe Traumatic Brain Injury Consensus Conference (SIBICC).