Cerebral perfusion pressure (CPP) is the net pressure gradient that drives oxygen delivery to cerebral tissue. It is the difference between the mean arterial pressure (MAP) and the Intracranial Pressure (ICP), measured in millimeters of mercury (mm Hg). Maintaining appropriate CPP is critical in the management of patients with intracranial pathology, including traumatic brain injury, and with hemodynamic distress, such as shock. Normal CPP lies between 60 and 80 mm Hg, but these values can shift to the left or right depending on individual patient physiology. As CPP is a calculated measure, MAP and ICP must be measured simultaneously, most commonly by invasive means. Maintaining adequate CPP in clinical situations of intracranial pathology with deranged ICP or in hemodynamically unstable conditions will decrease the risk of ischemic brain injury.

• CPP = MAP - ICP

Physiology

CPP and ICP: The CPP, at its most basic, is dependent on the ICP and mean arterial pressure and its normal range is 60 to 80 mm Hg. Under normal conditions, the ICP is between 5 and 10 mm Hg and thus has less of an impact on CPP than MAP for clinical situations not involving intracranial pathology. ICP is usually directly measured via intracranial pressure transduction. Physiologically, ICP is a function of intracranial compliance. Intracranial compliance is the relationship between ICP and volume in the intracranial cavity; including cerebrospinal fluid (CSF), brain tissue and arterial and venous blood volume.   As the skull is a fixed and rigid anatomic space, ICP will increase as intracranial volume increases, and intracranial compliance decreases. As the ICP increases (or intracranial compliance decreases), CPP will decrease.

Several mechanisms ensure that ICP remains in the normal range for as long as possible, during periods of changing intracranial volume and compliance. As volume adds to the intracranial space, CSF can move into the spinal subarachnoid space, leaving the ICP relatively unchanged. As volume increases (a growing space-occupying lesion, brain tissue edema or blood), this mechanism becomes overwhelmed, and ICP starts to increase sharply.

Cerebral blood flow (CBF) is also a critical factor in ICP homeostasis. Cerebral auto-regulation ensures a steady flow of blood to the brain over a wide range of physiologic changes and disturbances. When blood pressure decreases, auto-regulation causes cerebral vasodilation and an increase in CBF and cerebral blood volume, thus maintaining ICP and CPP. When blood pressure increases, auto-regulation causes cerebral vasoconstriction and a decrease in CBF with a resulting decrease in cerebral blood volume, also maintaining ICP and CPP. Too much alteration outside of normal CBF ranges can lead to brain ischemia and injury.[1]

CPP and MAP: As ICP in normal ranges is a relatively small number, the CPP is much more dependent on the mean arterial pressure. MAP is the average blood pressure during one cardiac cycle and can be directly measured through invasive hemodynamic monitoring or can be calculated as the systolic blood pressure, plus two times the diastolic blood pressure, divided by three. The normal range of MAP is 70 to 100 mm Hg.

The mean arterial pressure is much more likely to change during day-to-day activities such as exercise, rest and stress. However, if ICP remains constant, mean arterial pressure can change across its relatively wide range of normal without dramatically decreasing or increasing CPP. In fact, CPP and CBF will remain relatively unchanged across a wider range of MAP (50 – 150 mm Hg) than normal due to cerebral auto-regulation and vasoconstriction or vasodilation of cerebral vasculature.

For patients with hypertension, the auto-regulation setpoint shifts, therefore, a lowering of mean arterial pressure relative to the patient’s normal mean arterial pressure will cause vasodilation to increase CBF. Patients who have lower than normal mean arterial pressure at baseline will have auto-regulatory vasoconstriction in response to an increase in their relative normal MAP, to return CBF to baseline. Thinking about CBF and CPP in the context of the patient’s normal MAP is clinically relevant regarding management of intracranial pathology and hemodynamic derangements.

Monitoring cerebral perfusion pressure requires measuring both the MAP and the ICP. The MAP can be measured directly through invasive hemodynamic means, most often cannulation of a peripheral artery such as the radial or femoral artery. The MAP can also be measured indirectly with a noninvasive blood pressure cuff and applying the previously mentioned formula using the systolic and diastolic blood pressures.

Intracranial pressure is usually measured invasively through an intracranial pressure transduction device. The most common and most accurate method is with an intraventricular monitor. As such, intraventricular measurement of ICP is the current gold standard.[2] An intraventricular catheter is inserted into a hole drilled into the skull, and then into the lateral ventricle to directly measure the pressure of the CSF. The advantage of an intraventricular catheter is that CSF can be removed, if needed, to decrease ICP in the acute setting.  Disadvantages include a risk of bleeding, infection, and difficulty with proper placement if the ICP is very high. Other options include intra-parenchymal and sub-dural monitors.

ICP can be measured non-invasively by several methods, including, most-commonly, transcranial Doppler ultrasonography (TCD). TCD utilizes a temporal window to measure the velocity of blood flow through the middle cerebral artery. Systolic and diastolic flow velocity and mean flow velocity are used to calculate a pulsatility index. The pulsatility index has been reported to correlate strongly with ICP in some studies and poorly correlate with ICP in other studies. Therefore, it is not recommended to use TCD alone as a substitute for direct ICP measurement.[3][4]

Ideally, invasive monitoring of the MAP through an arterial cannula and invasive monitoring of the ICP through an intraventricular catheter will give a continuous and accurate calculation of CPP.

Two general categories of pathologic derangement exist wherein management of CPP is vital: intracranial pathology, where ICP management is most important; and hemodynamic instability/shock, where MAP management is most important.

Intracranial pathology includes space-occupying lesions such as tumors, epidural and subdural hematoma or acute intraparenchymal hemorrhage and cerebral edema as seen after ischemic injury, traumatic brain injury or severe hepatic encephalopathy. In these cases, adequate CPP is dependent on lowering the ICP back to a reasonably normal range as quickly as possible, while maintaining an adequate MAP. While CPP has a range of normal, it is important to remember that each patient’s brain tissue has a CPP that is “normal” in the context of that individual patient’s physiology, which may be influenced by other medical problems such as hypertension or vascular disease. As such, there is a push towards more dynamic management of CPP using the patient’s own auto-regulatory capacity.[5]  These methods involve more frequent and sophisticated monitoring and may not be available for widespread use.

In the setting of substantial traumatic brain injury, for example, significant cerebral edema can decrease intracranial compliance and overcome initial CSF shunting measures, producing an elevated ICP (intracranial hypertension). Auto-regulatory mechanisms may or may not function normally, and if ICP remains elevated, CPP will decrease causing further injury through an ischemic mechanism. In this case, in addition to initiating ICP lowering measures, it is important to avoid hypotension (MAP – ICP = CPP) and in some cases, allowing hypertension is reasonable.

In cases of hemodynamic instability, the ICP is relatively stable as cerebral auto-regulation is intact. In the setting of hypotension, the MAP decreases due to blood loss (hemorrhagic shock), intravascular leak (distributive shock) or decreased cardiac output (cardiogenic shock) and the CPP decreases as well. It is the relationship between MAP and CPP that drives resuscitation guidelines to recommend maintaining a MAP greater than or equal to 65 mm Hg. Assuming a normal ICP, this threshold should guarantee a CPP of 55 to 60, the minimum needed to prevent cerebral ischemic injury. As in the case of ICP and cerebral auto-regulation, MAP goals should be within the context of an individual patient’s baseline hemodynamic function. Patients with untreated hypertension should have higher MAP goals to maintain appropriate CBF and CPP.