Meaning of Intracranial Pressure-to-Blood Pressure Fisher-Transformed Pearson Correlation–Derived Optimal Cerebral Perfusion Pressure: Testing Empiric Utility in a Mechanistic Model

OBJECTIVES: Time-averaged intracranial pressure-to-blood pressure Fisher-transformed Pearson correlation (PR(x)) is used to assess cerebral autoregulation and derive optimal cerebral perfusion pressure. Empirically, impaired cerebral autoregulation is considered present when PR(x) is positive; greater difference between time series median cerebral perfusion pressure and optimal cerebral perfusion pressure (Δ(CPP)) is associated with worse outcomes. Our aims are to better understand: 1) the potential strategies for targeting optimal cerebral perfusion pressure; 2) the relationship between cerebral autoregulation and PR(x); and 3) the determinants of greater Δ(CPP). DESIGN: Mechanistic simulation using a lumped compartmental model of blood pressure, intracranial pressure, cerebral autoregulation, cerebral blood volume, Paco(2), and cerebral blood flow. SETTING: University critical care integrative modeling and precision physiology research group. SUBJECTS: None, in silico studies. INTERVENTIONS: Simulations in blood pressure, intracranial pressure, Paco(2), and impairment of cerebral autoregulation, with examination of “output” cerebral perfusion pressure versus PR(x)-plots, optimal cerebral perfusion pressure, and Δ(CPP). MEASUREMENTS AND MAIN RESULTS: In regard to targeting optimal cerebral perfusion pressure, a shift in mean blood pressure or mean intracranial pressure with no change in mean blood pressure, with intact cerebral autoregulation, impacts optimal cerebral perfusion pressure. Second, a positive PR(x) occurs even with intact cerebral autoregulation. In relation to Δ(CPP), for a given input blood pressure profile, with constant intracranial pressure, altering the degree of impairment in cerebral autoregulation or the level of Paco(2) maintains differences to within ±5 mm Hg. Change in intracranial pressure due to either an intermittently prolonged pattern of raised intracranial pressure or terminal escalation shows Δ(CPP) greater than 10 mm Hg and less than –10 mm Hg, respectively. CONCLUSIONS: These mechanistic simulations provide insight into the empiric basis of optimal cerebral perfusion pressure and the significance of PR(x) and Δ(CPP). PR(x) and optimal cerebral perfusion pressure deviations do not directly reflect changes in cerebral autoregulation but are, in general, related to the presence of complex states involving well-described clinical progressions with raised intracranial pressure.