Impaired cerebral autoregulation following traumatic brain injury (TBI) in adults has been linked to worse global outcome. Continuously updating indices of cerebrovascular reactivity provide a convenient and continuous metric regarding an individual patients’ autoregulatory status. To date, the vast majority of the literature has focused on pressure reactivity index (PRx), which has emerged as the “gold standard” for continuous monitoring of cerebrovascular reactivity in adult TBI, but many questions concerning its clinical utility remain unanswered. The focus of this thesis was to address some of these previously unanswered questions, using data from experimental models and from multi-modality monitoring (MMM) in adult TBI patients.

Specific questions addressed in this thesis include: [A] Do other ICP-derived indices to assess cerebrovascular reactivity exist? [B] Do ICP-derived indices actually measure autoregulation? [C] What are the inter-index relationships between various MMM techniques? [D] Can one estimate/predict the “gold standard” invasive PRx using non-invasive means? [E] What are the critical thresholds associated with outcome for ICP derived indices? [F] Are any specific ICP derived index/indices superior for outcome prediction? and [G] What role do intra-cranial (IC) and extra-cranial (EC) injury burden play in driving autoregulatory function in TBI?

These studies evaluated a newly described index derived from pulse amplitude of ICP and cerebral perfusion pressure (CPP), RAC, which provides information regarding both cerebrovascular reactivity and compensatory reserve. Using experimental models of arterial hypotension and IC hypertension, it was demonstrated that the three ICP derived indices (including RAC) of cerebrovascular reactivity measure the lower limit of autoregulation (LLA), providing some of the first evidence to validate these indices as measures of autoregulation. It still remains unclear as to whether these indices can measure the upper limit of autoregulation (ULA).

Indices derived from MMM display reproducible inter-index relationships between various populations of adult TBI patients. Transcranial Doppler (TCD) based systolic flow index is most closely associated with ICP indices, while cortical autoregulation (measured using laser Doppler) is more closely linked to mean flow index. Given these relationships and the potential for non-invasive measurement of systolic flow index, attempts at modelling the “gold standard” PRx were made. From this, it is possible to both estimate and predict PRx using non-invasive systolic flow index, employing complex time-series techniques.

Outcome analysis showed that RAC provides superior outcome prediction, with more stable critical thresholds, compared to all other ICP derived indices. Furthermore, IC injury markers (subarachnoid hemorrhage thickness, diffuse axonal injury, and presence of subdural hematoma) were associated with impaired cerebral autoregulation as measured by ICP derived indices, implicating diffuse cerebral injury as a driver of impaired reactivity. The data also suggest that EC injury burden may play a role in impairment of cerebrovascular reactivity.