Critical cerebral perfusion pressure at high intracranial pressure measured by induced cerebrovascular and intracranial pressure reactivity

Abstract

Objectives: The lower limit of cerebral blood flow autoregulation is the critical cerebral perfusion pressure at which cerebral blood flow begins to fall. It is important that cerebral perfusion pressure be maintained above this level to ensure adequate cerebral blood flow, especially in patients with high intracranial pressure. However, the critical cerebral perfusion pressure of 50 mm Hg, obtained by decreasing mean arterial pressure, differs from the value of 30 mm Hg, obtained by increasing intracranial pressure, which we previously showed was due to microvascular shunt flow maintenance of a falsely high cerebral blood flow. The present study shows that the critical cerebral perfusion pressure, measured by increasing intracranial pressure to decrease cerebral perfusion pressure, is inaccurate but accurately determined by dopamine-induced dynamic intracranial pressure reactivity and cerebrovascular reactivity.

Design: Cerebral perfusion pressure was decreased either by increasing intracranial pressure or decreasing mean arterial pressure and the critical cerebral perfusion pressure by both methods compared. Cortical Doppler flux, intracranial pressure, and mean arterial pressure were monitored throughout the study. At each cerebral perfusion pressure, we measured microvascular RBC flow velocity, blood-brain barrier integrity (transcapillary dye extravasation), and tissue oxygenation (reduced nicotinamide adenine dinucleotide) in the cerebral cortex of rats using in vivo two-photon laser scanning microscopy.

Setting: University laboratory.

Subjects: Male Sprague-Dawley rats.

Interventions: At each cerebral perfusion pressure, dopamine-induced arterial pressure transients (~10 mm Hg, ~45 s duration) were used to measure induced intracranial pressure reactivity (Δ intracranial pressure/Δ mean arterial pressure) and induced cerebrovascular reactivity (Δ cerebral blood flow/Δ mean arterial pressure).

Measurements and main results: At a normal cerebral perfusion pressure of 70 mm Hg, 10 mm Hg mean arterial pressure pulses had no effect on intracranial pressure or cerebral blood flow (induced intracranial pressure reactivity = -0.03 ± 0.07 and induced cerebrovascular reactivity = -0.02 ± 0.09), reflecting intact autoregulation. Decreasing cerebral perfusion pressure to 50 mm Hg by increasing intracranial pressure increased induced intracranial pressure reactivity and induced cerebrovascular reactivity to 0.24 ± 0.09 and 0.31 ± 0.13, respectively, reflecting impaired autoregulation (p < 0.05). By static cerebral blood flow, the first significant decrease in cerebral blood flow occurred at a cerebral perfusion pressure of 30 mm Hg (0.71 ± 0.08, p < 0.05).

Conclusions: Critical cerebral perfusion pressure of 50 mm Hg was accurately determined by induced intracranial pressure reactivity and induced cerebrovascular reactivity, whereas the static method failed.

Figure 1.

Static autoregulation curves for cerebral perfusion pressure (CPP)-intracranial pressure (ICP) group (CPP decreased by ICP increase, n = 12 rats) and CPP-mean arterial pressure (MAP) group (CPP decreased by MAP reduction, n = 7 rats). Data were normalized to baseline CPP of 70 mm Hg obtained before any manipulation (mean ± SEM, *p < 0.05).

Figure 2.

Dopamine-induced intracranial pressure reactivity (iPRx) (A) (min/max range: a [0.65, 1.95]; b [18.31, 6.10]; and c [0.00, 3.00]) and cerebrovascular reactivity (iCVRx) (B) (min/max range: a [0.75, 2.25]; b [–14.44, 4.81]; and c [0.00,3.00]) in the cerebral perfusion pressure (CPP)-intracranial pressure (ICP) group (CPP reduced by ICP elevation). Each circle represents one dopamine-induced test (nine tests per rat, total 12 rats). Trend line is the fitted sigmoidal (sigmoid, five variables) to all data points.

Figure 3.

Dopamine-induced intracranial pressure reactivity (iPRx) (A) and cerebrovascular reactivity (iCVRx) (B) in the cerebral perfusion pressure (CPP)-mean arterial pressure (MAP) group (CPP reduced by MAP decrease). Each circle represents one test (nine tests per rat, total seven rats). Trend line is the fitted polynomial (third order) to all data points.

Figure 4.

Changes in microvascular shunt (MVS)/capillary (CAP) flow ratio showing that decrease of cerebral perfusion pressure (CPP) by increasing intracranial pressure (ICP) resulted in a stagnation of CAP flow and an increase of MVS flow (CPP-ICP group, n = 12). The CPP decrease by mean arterial pressure (MAP) reduction reduced blood flow in all cerebral vessels (CPP-MAP group, n = 7). Mean ± SEM, *p < 0.05, **p < 0.01, compared to a baseline CPP of 70 mm Hg.