Point-Counterpoint: Cerebral perfusion pressure is a high-risk concept

Cerebral blood flow (CBF), fundamental for neuronal activity, is a product of complex mechanisms of cerebrovascular response such as autoregulation (CA) and neurovascular coupling, responsible to adjust the cerebral blood flow according to changes in systemic arterial blood pressure, intracranial vascular resistance, neuronal metabolic demand, ¹ as well as the volumes of the intracranial content. ² Therefore, as a concept, cerebral perfusion pressure (CPP) is highly relevant, to highlight the fact that the pressure difference driving CBF cannot be assumed to be given solely by BP. The quantitative expression of this concept though, has become dogmatic and questioning its generalizability should be encouraged to protect patients from less-than-optimal decision making.

The brain circulation differs from most organs, where blood flow is driven only by the difference between the BP and the capillary venous pressure (CVP). ³ As the brain is encapsulated by a rigid skull, a pressure gradient in the tissue is developed, usually expressed as intracranial pressure (ICP), which is normally equal or higher than CVP . Due to the Starling resistor, or waterfall phenomena, ICP then becomes the downstream pressure ³ and for this reason would justify expressing CPP as the difference between BP and ICP, especially in the case of intracranial hypertension. ⁴

Qualitatively, the role of elevated ICP in limiting CBF has been known for many decades. ⁵ The problem lies in the general application of BP-ICP as the determinant of CBF in neurocritical care, when considering patients limited in mobility, sedated and under mechanical ventilation, presenting substantial anatomical and functional impairments in cerebral circulation. ² Moreover, it is well known that hemodynamic changes following brain injuries are regionally different, reducing the accuracy of assumptions based on generic information that considers the global cerebral condition rather than focal needs. ⁵

The intracranial pressure-volume curve is highly non-linear, with an exponential-like shape. As a consequence, when intracranial volume increases due to vasodilation, edema, hematoma or other space occupying lesions, even small changes in its determinants, such as CBF, can lead to abnormally high increases in ICP. Under these circumstances, how safe is it to enforce a recommendation of a fixed CPP target ² ? The complexity of the cerebral circulation does not support this inflexible recommendation. As an example, a patient with ICP of 30 mmHg has a completely different intracranial ‘millieu’ than a patient with ICP of 10 mmHg, including effects on the production, circulation and reabsorption of CSF. Aiming at a CPP target of 60–80 mmHg for both would incur in a possibly adverse approach for the more critical patient, since the formula provides a misleading sense of BP ‘compensation’ for the high ICP. ⁶

Considering what was mentioned above, cerebrovascular physiological properties are powerful arguments against CPP = BP–ICP. It was demonstrated in severely brain injured patients that even with CA not being completely absent, the regulation and control of CBF responds much less to changes in ICP than to changes in BP. ⁶ Moreover, the contractile vascular smooth muscle and pericytes can lead to the collapse of arterioles and capillaries at BP much higher than 0 mmHg, the so-called critical closing pressure (CrCP), which is not determined exclusively by ICP, but presents a strong correlation with it. ⁴ Probably a more rigorous and accurate way to represent CPP would be the difference between BP and CrCP.^7,8

Returning to the neurocritical patient, in addition to CA impairment, several other factors can influence CBF. Hypercapnia leads to vasodilation and hence, increases in CBF mediated by reductions in CrCP.^1,4,7 Head position can influence hydrostatic pressure, venous drainage and changes in ICP. Unless closely controlled, these factors, together with hypoxia, may result in edema, intracranial hypertension and ischemia. ⁵

The complexity of CBF control is further enhanced in clinical practice, where in an environment of brain injury, the inflammatory response certainly has a major effect. Thus, the argument to decompose the formula of CPP into multiple influences that drive the effective downstream pressure, instead of relying on just one single variable (ICP) is more than justified. More importantly, the effort to make CPP a therapeutic target, rather than a monitoring parameter, collected in a multimodal approach, is dangerous because it ignores the complexity of the system bringing the risk to install erroneous treatment, which could lead to worse clinical outcomes.

In addition, in clinical settings, the BP is routinely measured in upper limbs and when not possible, in the lower limbs. Spence demonstrated that the brain circulation presents with pressure gradients because of multiple branching, leading to mean pressures in arterioles as half of the value of brachial arteries. ⁹ Furthermore, this gradient may be further enhanced due to other variables such as head positioning ¹⁰ and pathological conditions, as cerebral vasospasm or arterial occlusion, which lead to significant changes in the distal pressure of the affected segment. These are reasons why the estimated CPP would not represent the real hemodynamics of all territories. All these aspects highlight the complexity of cerebral hemodynamics which demands a multiparametric approach for its holistic assessment.

In conclusion, better understanding of cerebrovascular physiology is needed to underpin clinical recommendations. Whilst CPP is a valuable qualitative concept, its quantification as CPP = BP–ICP, without taking into consideration the multi-faceted complexity of the cerebral circulation, is not only bad science, it also carries risks to our patients.