Cerebral blood flow and its autoregulation - when will there be some light in the black box?

When considering autoregulation, it is interesting to first consider the cerebral perfusion of a giraffe. Although their necks are about 2.5 m long, they must be able to drink water from the ground level of the oasis and then eat leaves from trees, causing large changes in cerebral perfusion pressure. Fortunately nature has provided them with several cardiovascular, anatomical and physiological adaptions to enable them to do so without fainting.¹

In most cases our patients are in the supine position, but we also have to take care of patients in extreme Trendelenburg positions (e.g. for laparoscopic prostate surgery and (semi-)sitting positions for shoulder and cerebellar procedures). This can affect cerebral circulation, especially in the elderly, for hours. Furthermore, we have patients with compromised cerebral autoregulation as a result of pathological conditions, and our anaesthetics can affect autoregulation as well. So there is considerable risk of cerebral hyper- and hypo-perfusion during perioperative care. Nevertheless, serious neurological damage after general anaesthesia because of global or regional cerebral ischaemia is a rare complication: although the incidence of overt stroke in the perioperative setting is below 1% in non-cardiac surgery, strokes do have a devastating effect on patients' quality and duration of life. Moreover, brain magnetic resonance imaging studies suggest that 1 in 10 elderly patients has a (subclinical) covert perioperative stroke.²

The World Health Organization considers that because of an ageing population, by 2030 chronic diseases will affect the lives of nearly 52 million inhabitants in the European region. More than 80% of people aged above 65 yr will suffer from chronic diseases, especially of the cardiovascular and neurovascular systems.³ Many of our patients in the future will have disturbed cerebral autoregulation. There is thus a serious need for more research in the field in perioperative cerebrovascular pathophysiology, monitoring techniques and therapeutic strategies.

Cerebral oxygen delivery and consumption rate are 10 times higher than global body values, and there are no oxygen stores in the brain such as myoglobin, which stores oxygen in the muscle. Consequently, the rate of oxygen delivery from blood to brain tissue critically depends on adequate cerebral blood flow (CBF), cerebral perfusion pressure (CPP) and cerebral autoregulation and the vessel-to-tissue oxygen partial pressure (PtiO₂) gradient and the efficiency of oxygen transfer from the capillary bed.

Cerebral autoregulation is the essential local regulatory mechanism that keeps CBF relatively constant despite large changes in systemic arterial pressure. Even short-term fluctuations in CPP cause adjustments in cerebrovascular resistance via complex neurogenic, myogenic, and metabolic mechanisms to preserve a stable CBF.⁴ This is the reason why humans can run, dance, read a book or sleep with nearly unchanged CBF. Even a prolonged handstand during a yoga lesson with great changes of cerebrovascular pressures will cause rapid adaption by cerebral autoregulation. Despite its importance, cerebral autoregulation physiology and pathophysiology are still not fully understood. However, there are some interesting approaches helping us understand cerebral autoregulation better.

One of these approaches distinguishes between static and dynamic cerebral autoregulation.⁴ However, this is an experimental, not a physiological, definition. Static cerebral autoregulation describes the relationship between mean CPP and CBF under steady-state conditions, whilst dynamic cerebral autoregulation refers to the vascular responses to higher frequency components of steady-state spontaneous blood pressure, or to dynamic changes in blood pressure (e.g. with changes in posture, respiratory changes, or even closed vs open eyelids). However, there are no data that explicitly indicate that the short- and long-term regulation of CBF is based on different physiologic pathways.

Cerebral perfusion is regulated by two important principles: one is flow-metabolism coupling, an adaptive mechanism to provide more blood to the more active parts of the brain and vice versa. The other one is cerebral autoregulation, keeping CBF stable over a broad range of CPP. Both of these mechanisms have their limitations and both might be altered under anaesthesia.

General anaesthesia is a non-physiological drug-induced state: I.V. anaesthetics reduce cerebral electrical activity, CBF, cerebral oxygen delivery and consumption by nearly 30%, because of the neurovascular-metabolic coupling mechanism. Global CBF is subsequently reduced from 50 to 40 ml 100 g⁻¹ min⁻¹. A temporary reduction of mean arterial pressure <70 mm Hg, or even <60 mm Hg after i.v. induction of anaesthesia, is unfortunately a common side-effect, especially in older patients.⁵ The resulting low cerebral perfusion pressure (CPP) can exceed the limits of autoregulation and cause inadequate cerebral perfusion, because cerebral vasomotor tone is possibly exhausted (maximal dilation). Nevertheless, most of our patients show a stable cerebral tissue oxygen saturation after induction of general anaesthesia.⁶

In routine daily practice, anaesthetists rely on systolic and mean arterial blood pressure as the main determinants of cerebral perfusion. Sometimes we also measure tissue-oxygenation by Near Infrared Spectroscopy (NIRS) or electrical activity by anaesthesia depth monitoring devices, but all those only provide a rough estimate of the adequacy of cerebral perfusion.

A monitoring device that can reliably indicate whether cerebral perfusion is adequate or not during general anaesthesia would be a useful addition to the anaesthetists’ monitoring armamentarium. Even more powerful would be a device that can determine whether the autoregulation of CBF is functioning normally or not, when affected by the patient´s pathology or the anaesthetic drugs used.

An ideal monitor of CBF and cerebral autoregulation would be easy to use, fast-reacting (real-time), continuously useable, noninvasive, not too expensive, and would not interfere with the surgical field (especially in neurosurgery/neuroanaesthesia) or with the standard anaesthesia regimen.

Transcranial Doppler sonography measures flow velocity in the basal cerebral arteries. It is a useful technique for day-to-day bedside assessment of critical conditions including vasospasm in subarachnoid haemorrhage, traumatic brain injury, acute ischaemic stroke, and brainstem death. Cerebral blood flow velocity of the middle cerebral artery (Vmca) and its indices are routinely used to assess components of cerebral circulation. Although Vmca is not a direct measure of CBF, changes in flow velocity generally correlate well with changes in CBF, except for specific situations that can affect middle cerebral artery diameter such as vasospasm, hypercapnia, migraine attacks, and nitroglycerine or other vasoactive agents. Furthermore, transcranial Doppler waveform analysis has been investigated as a technique for critical closing pressure or zero flow pressure estimation, which could represent one of its most useful applications outside the intensive care setting.⁷ It also allows investigating cerebrovascular autoregulation in setting of carotid disease and syncope.

Examining the functional capacity of the cerebrovascular autoregulatory system by altering blood pressure is difficult and possibly hazardous as a routine clinical procedure. In this edition of the British Journal of Anaesthesia, Hermanides and colleagues⁸ present a novel method for the intraoperative assessment of cerebral autoregulation by paced breathing. Their approach is innovative and demonstrates that cerebral autoregulation can be reliably quantified from blood pressure oscillations amplified by positive pressure ventilation. This is a great step forward. However, this cerebral autoregulation measurement technique is not yet ready to be implemented in daily clinical practice. Only a few anaesthetists are well trained in transcranial Doppler CBF measurement. A ventilation rate of six Bpm is not suitable for every patient. The technique is validated under steady-state conditions of three min, but cerebral autoregulation is most interesting in dynamic conditions such as large blood loss, low cardiac output, arterial hypotension, or vasoplegia. Some other limitations of their approach are discussed in their paper. However, this technique has some interesting features, which hopefully will inspire further developments so that we will finally be able to monitor CBF and cerebral autoregulation reliably in those patients who are most at risk: those with chronic neurological and cardiovascular diseases, those undergoing neurosurgery, and those with instable haemodynamics. With these findings, there is at least another spark of light in the black box of intracranial haemodynamics, but we will have to keep waiting for more light.

Declaration of interest

None to declare.

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