Cerebral blood flow

Cerebral blood flow (CBF) is around 15% of cardiac output and is affected by various factors. The main
ones are as follows:
• PaCO2: A high PaCO2 causes vasodilatation of blood vessels and increases CBF. A low PaCO2 causes
vasoconstriction. Reducing the PaCO2 from 5 to 4 kPa (38.5–30.5 mmHg) reduces CBF by almost 30%.
• Hypoxaemia: Below 6.7 kPa (51.5 mmHg) causes increasing CBF.
• Mean arterial pressure (MAP).
• Drugs.

The relationship of CBF to PaCO2, PaO2 and MAP is shown in Fig. 8.1. Like the kidneys, the brain
autoregulates blood flow so that it is constant between a MAP of 50 and 150 mmHg. CBF is regulated by
changes in the resistance of the cerebral arteries. Unlike the rest of the body, the larger arteries play a
main role in this autoregulation. Local chemicals, endothelial mediators and neurogenic factors are
thought to be responsible.

CBF is controlled by alterations in cerebral perfusion pressure (CPP) and cerebral vascular resistance (R):

CPP is the pressure gradient in the brain or the difference between the incoming arteries and the outgoing
veins:

CPP = MAP - Venous pressure

Venous pressure is equal to intracranial pressure (ICP), so CPP is usually expressed as:

CPP = MAP - ICP

Normal supine ICP is 7–17 mmHg and is frequently measured on neurointensive care units (ICUs). CPP
can then be calculated and manipulated.

Intracranial pressure
The skull is a rigid box and its contents are incompressible, therefore, ICP depends on the volume of
intracranial contents: 5% blood, 10% cerebrospinal fluid (CSF) and 85% brain. The Monro–Kellie doctrine,
named after two Scottish anatomists (see Fig. 8.2), states that as the cranial cavity is a
closed box, any change in intracranial blood volume is accompanied by an opposite change in CSF volume,
if ICP is to be maintained.

When ICP is raised the following occurs:

• CSF moves into the spinal canal and there is increased reabsorption into the venous circulation
• Compensatory mechanisms are eventually overwhelmed so further small changes in volume lead to
large changes in pressure (see Fig. 8.3)
• As ICP rises further, CPP and CBF decrease
• Eventually brainstem herniation (coning) occurs. The clinical features of acutely raised ICP are
headache, nausea and vomiting, confusion, and a reduced conscious level. This can occur in traumatic
brain injury, cerebral haemorrhage or infarction, meningitis/encephalitis, or quickly growing tumours. An
estimate of ICP can be made in patients with brain injury who are not sedated:

• Drowsy and confused with Glasgow Coma Score (GCS) 13–15: ICP
20mmHg
• GCS less than 8: ICP 30 mmHg.

Primary and secondary brain injury

Primary brain injury is the injury that has already occurred and has limited treatment. But the brain is
uniquely vulnerable to secondary insults and less capable of maintaining an adequate blood flow and
metabolic balance following injury. Research in the field of traumatic brain injury has shown that
preventing secondary brain injury can improve outcome for the patient. Secondary brain injury is, by
definition, delayed and therefore amenable to intervention. Examples of secondary brain injury include:
• Raised ICP
• Ischaemia
• Oedema
• Infection (e.g. in open fractures).
Following brain injury, neurones are rendered dysfunctional although not mechanically destroyed. If the
subsequent environment is favourable, many of these cells can recover. Preventing raised ICP and saving
the penumbra (the area around the primary injury with its compromised microcirculation) is important. An
uncontrolled increase in ICP and brainstem herniation is the major cause of death after traumatic brain
injury or intracerebral haemorrhage. In traumatic brain injury, the main precipitants of secondary injury
are hypotension and hypoxaemia. Hypoxaemia, as defined by oxygen saturations _93%, and hypotension,
as defined by a systolic BP of less than 90 mmHg, are associated with a statistically significant worse
outcome and are common at the scene of injury [1].

Principles of brain protection

Based on our knowledge of brain physiology and observations of traumatic brain injury, a set of measures
to protect the brain against secondary injury can be devised [2]. This can be applied to any kind of brain
injury, for example, subarachnoid haemorrhage (SAH), meningitis or stroke.

The aim of brain protection is to prevent:

• Raised ICP
• Cerebral ischaemia
• Cerebral oedema.
In addition, fever has been observed to worsen outcome in patients with brain injury, probably because
the cerebral metabolic rate for oxygen is increased and this exacerbates local ischaemia.
Raised ICP is caused by an increase in the volume of blood, CSF or brain tissue, so treatment is aimed at
reducing the volume of these three components and is summarised in Fig. 8.4.
Fig. 8.5 summarises these principles in an ABCDE format. Although most research has been done in
traumatic brain injury, these principles have also been successfully applied to medical conditions such as
meningitis with raised ICP [3], and current research is focussing on prevention of secondary brain
injury in stroke.

Experimental methods of brain protection

The cerebral metabolic rate for oxygen is reduced by hypothermia. Hypothermia has been used in the past
for cerebral protection during complex cardiac and neurosurgery. Animal models demonstrate its benefits
but actively cooling normothermic human subjects with brain injury has not yet been shown to improve
outcome [4]. However pyrexia is associated with an adverse outcome in brain injury [5] and therefore
should be treated with paracetamol and active cooling.
Hypertonic saline has been studied extensively in traumatic brain injury. The theory is that the hypertonic
solution will draw intracellular water into the intravascular space, reducing cerebral oedema and
expanding intravascular volume. The results of clinical trials have been mixed [6]. In patients with other
injuries such as haemorrhage or burns, resuscitation with hypertonic saline has adverse effects, so its use
is not recommended in the routine resuscitation of trauma victims.

The unconscious patient

A reduced conscious level is associated with potentially life-threatening complications (e.g. airway
obstruction and hypoxaemia, aspiration and immobilization injuries) which require urgent intervention.
Unconsciousness, or coma, is present when the GCS is 8 or less (see Fig. 8.6). Comatose patients should
be referred to the ICU.
The causes of non-traumatic coma (lasting more than 6 h) are [7]:
• Sedative overdose: 40%
• Hypoxic brain injury: 24%
• Cerebrovascular disease: 18%

• Metabolic coma (e.g. infection, diabetes, hepatic encephalopathy, hypothermia):

15%
• Others: 3%.

However, a slightly different pattern is observed in the elderly, who commonly become confused, drowsy
or unresponsive due to a wide range of conditions, most commonly infection and dehydration.
Seizures are an important, although less common, cause of coma, either because the patient is post-ictal
(which can be prolonged in the elderly) or has non-convulsive status epilepticus [8]. A systematic
approach is required in the management of an unconscious patient. As usual, the ABCDE system is used:
• A: assess and treat airway problems.
• B: assess and treat breathing problems.
• C: assess and treat circulation problems.
• D: assess disability (pupil size and reactivity, capillary glucose and the simple
Alert, responds to Voice, responds to Pain, Unresponsive (AVPU) scale) and treat any problems. The GCS
should be recorded once A, B and C are stable so that any later changes can be documented precisely. •
E: includes a full neurological examination. Certain clusters of signs may
point to a particular diagnosis (see Fig. 8.7).
Deliberation and diagnosis must not take precedence over the assessment and treatment of ABC
problems. For example, early antibiotic therapy in meningitis is crucial, however relieving airway
obstruction and giving i.v. fluid for hypotension is just as important.
The indications for tracheal intubation in patients with brain injury are the same as in any other patient,
that is GCS of 8 or less, airway problems and the need for ventilation, but in certain situations patients
may need intubation prior to transfer, for example, a deteriorating conscious level, bilateral mandible
fractures, bleeding into the airway or seizures.

Imaging in coma
Computed tomography (CT) and magnetic resonance imaging (MRI) are the two techniques used in
acutely ill adults. CT is the investigation of choice in trauma, subarachnoid haemorrhage (SAH) and
stroke. It is readily available, quick and virtually all patients can be scanned. MRI provides images in
several planes and provides superior grey/white matter contrast with a high sensitivity for most
pathological processes compared with CT. MRI would be the investigation of choice in suspected posterior
fossa lesions, seizures or inflammatory processes. MRI is also more sensitive for thin extradural
haematomas and diffuse axonal injury in trauma but requires special consideration for anaesthetised
patients because of the incompatibility of anaesthetic and monitoring equipment with the electromagnetic
field. Brain imaging is only undertaken if the patient is stable and a full evaluation has led to a differential
diagnosis. When imaging is requested, it should lead to a diagnosis or have the potential to change
management.