Ebook Oh''s intensive care manual (8/E): Part 2

51 
Acute cerebrovascular complications
Thearina de Beer

Cerebrovascular disease is common and its acute manifestation – stroke – produces considerable morbidity and mortality. Stroke is defined as an acute focal
neurological deficit caused by cerebrovascular disease,
which lasts for more than 24 hours or causes death
before 24 hours. Transient ischaemic attack (TIA) also
causes focal neurology, but this resolves within 24
hours. Stroke is the fourth largest cause of death in
the United Kingdom, the second largest worldwide
and is the most common cause of physical disability
in adults.1 Stroke can be categorised as ischaemic or
haemorrhagic (Table 51.1).
The main risk factors are increasing age, hypertension, ischaemic heart disease, atrial fibrillation,
smoking, diabetes, obesity, some oral contraceptives
and raised cholesterol or haematocrit.
PROGNOSIS IN ACUTE  
CEREBROVASCULAR DISEASE
Mortality after stroke averages 30% within a month,
with more patients dying after subarachnoid haemorrhage (SAH) or intracerebral haemorrhage than
after cerebral infarction, although survival to 1 year is
slightly better in the haemorrhagic group. In all types
of stroke, about 30% of survivors remain disabled to
the point of being dependent on others. Risk of stroke
increases with age and doubles every decade over the
age of 55.1 Thus stroke is often accompanied by significant age-related medical co-morbidity. In the past, this
may have been partially responsible for a relatively
non-aggressive approach to the treatment of stroke
patients, so the gloomy prognosis of stroke becomes
a self-fulfilling prophecy. The challenge for intensivists is to identify those patients who are most likely to

survive, and not to offer aggressive therapy to those
who are not. Stroke should be regarded as a medical
emergency. Patients should initially be treated in a
stroke unit as there is good evidence of reduction in
both mortality and dependency compared with those
treated in a general ward. The UK National Institute
for Health and Clinical Excellence (NICE) has published guidelines aimed at ensuring early diagnosis
and aggressive therapy.2

CEREBRAL INFARCTION
Infarction of cerebral tissue (ischaemic stroke) occurs
as a result of inadequate perfusion from occlusion of
cerebral blood vessels (large or small) in association
with inadequate collateral circulation. It may occur
due to cerebral thrombosis or embolism.
AETIOLOGY AND PATHOLOGY
CEREBRAL THROMBOSIS
Atherosclerosis is the major cause of major arterial
occlusion and most often produces symptoms if it
occurs at the bifurcation of the carotid artery or the
carotid syphon. Progressive plaque formation causes
narrowing and forms a nidus for platelet aggregation
and thrombus formation. Ulceration and rupture of the
plaque exposes its thrombogenic lipid core, activating
the clotting cascade. Hypertension and diabetes mellitus are common causes of smaller arterial thrombosis.
Rarer causes of thrombosis include any disease resulting in vasculitis, vertebral or carotid artery dissection
(either spontaneous or post-traumatic) or carotid occlusion by strangulation or systemic hypotension after
cardiac arrest. Cerebral venous thrombosis, responsible for less than 1% of strokes, may occur in hypercoagulable states, such as dehydration, polycythaemia,
thrombocythaemia, some oral contraceptive pills,
protein C or S deficiency, or antithrombin III deficiency

or vessel occlusion by tumour or abscess. Cerebral
infarction may also result from sustained systemic
hypotension from any cause, particularly if associated
with hypoxaemia.
CEREBRAL EMBOLISM
Embolism commonly occurs from thrombus or platelet
aggregations overlying arterial atherosclerotic plaques,
but 30% of cerebral emboli will arise from thrombus
in the left atrium or ventricle of the heart. This is very
likely in the presence of atrial fibrillation, left-sided
valvular disease, recent myocardial infarction, chronic
atrial enlargement or ventricular aneurysm. The


Abstract and keywords 651.e1
ABSTRACT

KEYWORDS

Stroke, whether it is ischaemic or haemorrhagic, is
an acute medical emergency, and great strides have
been made in its treatment in the last 10 years. It still
remains a high-ranking cause of death worldwide, but
outcomes have improved with the newer treatments.
When a stroke is suspected, a computed tomography
scan of the brain needs to be performed within an hour
of presentation, and what type of stroke it is will determine further management. Stroke patients should be
treated in hyperacute stroke centres with neurosurgical
support. Subarachnoid haemorrhage patients should
be in a neurosurgical centre with access to interventional neuroradiologists. With rehabilitation, the stroke

survivors can make a significant recovery.

Stroke
ischaemic stroke
haemorrhagic stroke
intracerebral haemorrhage
intracerebral bleed
subarachnoid haemorrhage
endovascular coiling
mechanical thrombectomy


652

Acute cerebrovascular complications

Table 51.1  Classification of stroke
ISCHAEMIC STROKE CAN
BE DIVIDED INTO FIVE
TYPES:

HAEMORRHAGIC
STROKE CAN BE DIVIDED
INTO TWO TYPES:

1. Large-artery
atherosclerosis
2. Cardioembolism
3. Small-vessel occlusion
4. Stroke of other

determined aetiologies
5. Stroke of
undetermined
aetiology

1. Intracerebral
haemorrhage (ICH)
2. Subarachnoid
haemorrhage (SAH)

presence of a patent foramen ovale or septal defects
allows paradoxical embolism to occur. Iatrogenic air
embolism may occur during cardiopulmonary bypass,
cardiac catheterisation or cerebral angiography. Embolisation may also occur as a complication of attempted
coil embolisation of cerebral aneurysms or arteriovenous malformations (AVMs) after SAH.
CLINICAL PRESENTATION
In cerebral thrombosis, there is initially no loss of consciousness or headache, and the initial neurological
deficit develops over several hours. Cerebral embolism may be characterised by sudden onset and rapid
development of complete neurological deficit. No
single clinical sign or symptom can reliably distinguish
a thrombotic from an embolic event.
Where infarction occurs in a limited arterial territory the clinical signs are often characteristic. The commonest site involves the middle cerebral artery, which
classically produces acute contralateral brachiofacial
hemiparesis with sensory or motor deficits, depending on the precise area of infarction. Infarction of the
middle cerebral territory leads to a dense contralateral
hemiplegia, contralateral facial paralysis, contralateral
hemianopia and ipsilateral eye deviation. Dominant
left-hemisphere lesions result in language difficulties
from aphasia, dysphasia, dysgraphia and dyscalculia.
Non-dominant right hemispheric lesions cause the

patient to neglect the left side, and failure to communicate with anyone approaching from that side.
In strokes involving the posterior fossa, the precise
pattern of symptoms depends on the arterial territories involved and the presence or absence of collaterals. The onset of symptoms, such as gait disturbance,
headache, nausea, vomiting and loss of consciousness,
may be very rapid. Venous thrombosis may occur,
particularly in the cerebral veins, sagittal or transverse
dural sinuses, causing headache, seizures, focal neurology and loss of consciousness. Other cognitive effects
of stroke include memory impairment, anxiety, depression, emotional lability, aprosody and spatial impairment. Bilateral brainstem infarction after basilar artery

thrombosis may produce deep coma and tetraparesis.
Pontine stroke may produce the ‘locked-in’ syndrome.
The precise clinical presentation depends on the size
of the infarcted area and its position in the brain. Vascular lesions, such as carotid dissection, can present
with ipsilateral Horner syndrome with facial pain, a
painful Horner’s from local stellate ganglion damage
or if there is significant ischaemia from impaired flow
or emboli, then with contralateral signs consistent
with infarction.3
INVESTIGATIONS
A full history and examination of the patient will
produce a differential diagnosis that will require specific investigations. The aim is to make the diagnosis,
establish the nature, size and position of the pathology,
so that correct treatment can target the effects of the
primary injury, and prevent extension of the lesion or
complications occurring.
BLOOD TESTS
A blood glucose test should be done to exclude diabetes and rule out hypoglycaemia as a cause for symptoms. A full blood count should be taken to look for
polycythaemia, infection or thrombocythaemia. A
raised erythrocyte sedimentation rate or C-reactive
protein level may indicate vasculitis, infection or carcinoma, warranting further appropriate investigations.

Cardiac enzymes and troponin should be taken after
an electrocardiogram (ECG). Urea and electrolytes, as
well as creatinine and liver function tests, should be
taken to rule out a metabolic component. A coagulation screen should also be taken together with serum
cholesterol, triglyceride and syphilis serology. Specific investigation for thrombophilia due to protein C,
protein S, Leiden factor V and antithrombin III abnormalities should be undertaken in patients with venous
thrombosis or patients with otherwise unexplained
cerebral infarction or TIA. A pregnancy test should be
performed on females under the age of 55.
ELECTROCARDIOGRAPHY
This may demonstrate atrial fibrillation, other arrhythmia or recent myocardial infarct.
ECHOCARDIOGRAPHY
Either transthoracic or transoesophageal echocardiography (TOE) may demonstrate mural or atrial appendage thrombus as a source of embolism. TOE is more
effective in detecting patent foramen ovale, aortic
arteriosclerosis or dissection. Base the decision to
perform echocardiography on history, ECG or physical findings.2
IMAGING
New guidelines suggest a computed tomography
(CT) brain scan within 1 hour of presentation with


Cerebral embolism
a suspected stroke. 2 These techniques are used to
distinguish infarction from haemorrhage. Tumour,
abscess or subdural haematoma may also produce
the symptoms and signs of stroke. Early scanning is
vital if interventional treatment, such as thrombolysis,
thrombectomy, anticoagulation, antiplatelet therapy or
surgery, is planned.
The CT scan may be normal or show only minor

loss of grey/white matter differentiation in the first 24
hours after ischaemic stroke, but haemorrhage is seen
as areas of increased attenuation within minutes. After
a couple of weeks, the CT appearances of an infarct or
haemorrhage become very similar and it may be impossible to distinguish them if CT is delayed beyond this
time. CT angiography (CTA) will often demonstrate
vascular abnormalities and vasospasm but multimodal
magnetic resonance imaging (MRI), a combination of
diffusion and perfusion-weighted MRI and magnetic
resonance angiography (MRA), is much more sensitive in demonstrating small areas of ischaemia. Timing
from the onset of symptoms and the exclusion of intracranial haemorrhage (ICH) determines the suitability
and benefit of thrombolysis.4 Where cerebral infarction has occurred as a result of venous thrombosis,
the best imaging technique is MRA. Any patient with
a stroke or TIA in the internal carotid artery territory
should have duplex Doppler ultrasonography, which
may demonstrate stenosis, occlusion or dissection of
the internal carotid. Where trauma is an aetiological factor reconstruction CT bone window views are
required to demonstrate any site of fracture-associated
vascular injury.
MANAGEMENT
There is strong evidence that admission to a specialised stroke care unit as soon as possible after the occurrence of a stroke provides a cost-effective reduction in
long-term brain damage and disability.2 In general,
only those patients with a compromised airway due to
a depressed level of consciousness or life-threatening
cardiorespiratory disturbances require admission to
medical or neurosurgical intensive care units (ICUs).
In either case, attention to basic resuscitation, involving stabilisation of airway, breathing and circulation,
is self-evident.
AIRWAY AND BREATHING
Patients with Glasgow Coma Scores (GCS) of 8 or less,

or those with absent gag or defects of swallowing (both
of which may occur at higher GCS), will require intubation to preserve their airway and to prevent aspiration. Where this requirement is likely to be prolonged,
early tracheostomy should be considered. Adequate
oxygenation and ventilation should be confirmed by
arterial blood gas analysis, and supplemental oxygen
prescribed if there is any evidence of hypoxia. If
hypercarbia occurs then ventilatory support to achieve

653

normocarbia is necessary to prevent exacerbation of
cerebral oedema. A multicentre international study
demonstrated that ICU mortality was 37% and hospital mortality was 45% for ventilated stroke patients; it
also demonstrated a longer ventilation time and higher
tracheostomy rate than non-neurological patients.5
CIRCULATORY SUPPORT
A large number of stroke patients will have raised
blood pressure (BP) on admission, presumably as an
attempt by the vasomotor centre to improve cerebral
perfusion. Hypertensive patients may have impaired
autoregulation and regional cerebral perfusion may
be very dependent on BP. The patient’s clinical condition and neurological status should determine treatment rather than an arbitrary level of BP. Current
recommendations are that emergency administration
of antihypertensive agents should be withheld unless
the systolic pressure is >220 mm Hg or the diastolic
pressure is >120 mm Hg. Aggressive lowering of BP
is not without risk and may result in the progression
of ischaemic stroke, so reduction should be monitored closely (not exceeding 15% of normal BP).6 It
would seem reasonable on physiological grounds to
avoid drugs that cause cerebral vasodilatation in that

they may aggravate cerebral oedema, although there
is no hard evidence for this. Cardiac output should
be maintained and any underlying cardiac pathology, such as failure, infarction and atrial fibrillation,
treated appropriately.
METABOLIC SUPPORT
Both hypo- and hyperglycaemia have been shown to
worsen prognosis after acute stroke; therefore blood
sugar levels should be maintained in the normal range
(<8.6 mmol/L).7 In the long term, nutritional support
must not be neglected, and early enteral feeding should
be instituted by nasogastric intubation if needed. In
the longer term, particularly where bulbar function is
reduced, percutaneous endoscopic gastrostomy may
be necessary.
ANTICOAGULATION
The routine use of prophylactic heparin in immobile
stroke patients should be avoided as the risk of intra­
cerebral bleeding is high. Intermittent pneumatic compression should be used for 30 days or until mobile.2
Anticoagulation can only be recommended in individuals where there is a high risk of recurrence, such
as in those patients with prosthetic heart valves, atrial
fibrillation with thrombus or those with thrombophilic
disorders. A CT scan must be obtained prior to commencing therapy to exclude haemorrhage, and careful
monitoring used. In patients with large infarcts, there
is always the risk of haemorrhage (haemorrhagic conversion) into the infarct and early heparinisation is
best avoided. Aspirin 160–300 mg should be given
within 48 hours after thrombolysis and continued for 2


654

Acute cerebrovascular complications

weeks while antithrombotic therapy is commenced. If
the patient is intolerant of aspirin, an alternative, such
as clopidogrel, should be used.2
THROMBOLYSIS
Thrombolysis with intravenous recombinant tissue
plasminogen activator (rtPA alteplase) is now an established treatment for acute ischaemic stroke.8 There are
specific inclusion and exclusion criteria. Inclusion criteria are a diagnosis of ischaemic stroke causing measurable neurological deficit, age over 18 with an onset
of symptoms to treatment time of less than 3 hours.
Patients should be excluded if there is a history of
head trauma or stroke (ischaemic or haemorrhagic)
in the previous 3 months, evidence of subarachnoid
or ICH, intracranial neoplasma, AVM or aneurysm,
recent intracranial or intraspinal surgery, arterial puncture in a non-compressible site in the past 7 days, any
active bleeding or bleeding diathesis including platelet
count less than 100,000/mm3, heparin within 48 hours,
current anticoagulant therapy, hypoglycaemia or multilobar infarction (more than one-third of a cerebral
hemisphere) on CT scan. Relative contraindications
include minor or rapidly improving stroke symptoms,
seizure at time of stroke with residual postictal signs,
serious trauma or major surgery in the past 14 days,
gastrointestinal or urinary tract bleeding in the past
21 days, or myocardial infarction within the past 3
months or pregnancy.
There is some evidence for improved clinical
outcome after rtPA use between 3 and 4.5 hours after
symptom onset, although the degree of clinical benefit
is less.6 Patients must be in an environment where they
can be monitored for potential complications, the most

serious of which is ICH. The inclusion criteria must
be adhered to, age <80 years, not having a history of
diabetes AND stroke, not taking warfarin or other oral
anticoagulant (National Institutes of Health Stroke
Score, NIHSS), ≤25. This risk is reduced where there is
strict adherence to the inclusion and exclusion criteria
and the appropriate dose used.
ENDOVASCULAR THERAPY
Several studies have shown positive results with
mechanical thrombectomy in immediate and 90-day
functional outcome, specifically for patients with a
large artery proximal occlusion in addition to thrombolysis and for patients who have contraindications to
thrombolysis but not mechanical thrombectomy.2,9,10
This procedure is available only in specialist neuroradiology departments, which have the support of a
neurosurgical centre.
DECOMPRESSIVE CRANIECTOMY
Some patients with malignant middle cerebral artery
infarction syndrome (MMCAS) (Fig. 51.1) may benefit
from decompressive craniectomy, especially patients
with large middle cerebral artery territory infarcts

Figure 51.1  Malignant MCA infarct.

aged <60 years. Decompressive craniectomy must be
done within 48 hours of symptom onset. The number
needed to treat (NNT) for survival is 2 and for severe
disability is 6. Untreated, MMCAS has a mortality of
80% and it is suggested craniectomy can reduce mortality to around 30%, but with residual neurological
deficit. This procedure is limited to specialist centres.
MMCAS development is predicted by middle cerebral

artery (MCA) territory stroke of >50%, a perfusion
deficit of >66% on CT, an infarct volume of >145 mL
within 14 hours and >82 mL within 6 hours of onset.
Electroencephalography (EEG) and tissue cerebral
tissue oxygenation have been used to predict cerebral
oedema; intracranial pressure (ICP) monitoring has
not been proven to change the outcome. Craniectomy
has to be large enough to extend past the margins
of the infarct. This seems to be well tolerated even
after thrombolysis. There is no difference in outcome
whether dominant or non-dominant hemispheres are
involved. The patients who survive after craniectomy
have moderate to severe disability and may have
a high incidence of psychological complications. A
recent study has shown benefit in this procedure for
patients over 60 years.11 Whether this is acceptable to
patients has not been studied.12
Other forms of surgical intervention proven to be
effective in making more intracranial space and reducing ICP are drainage of secondary hydrocephalus by
extraventricular drain (EVD) insertion or evacuation


Intracerebral haemorrhage

655

of haemorrhage into infarcted areas, resulting in new
compressive symptoms. This is especially useful in the
posterior fossa where the room for expansion of mass
lesions is limited by its anatomy.

COMPLICATIONS
Local complications include cerebral oedema, haemorrhage into infarcted areas or secondary hydrocephalus.
General complications include bronchopneumonia,
aspiration pneumonia, deep-vein thrombosis, urinary
tract infections, pressure sores, contractures and
depression. Stroke patients who are ventilated seem
particularly susceptible to ventilator-acquired pneumonia.13 A team approach of specialist nursing, physiotherapists, occupational and speech and language
therapists is best able to avoid these complications.
SPONTANEOUS INTRACRANIAL
HAEMORRHAGE
Spontaneous ICH producing stroke may occur from
either intracerebral haemorrhage (10%) or SAH (5%).
INTRACEREBRAL HAEMORRHAGE
The incidence of intracerebral haemorrhage is about
9/100,000 of the population, mostly in the age range
of 40–70 years, with an equal incidence in males and
females.

Figure 51.2  Devastating intracerebral haemorrhage.

AETIOLOGY AND PATHOLOGY

CLINICAL PRESENTATION

The commonest cause is the effect of chronic systemic
hypertension. This results in degeneration of the walls
of vessels or microaneurysms, by the process of lipohyalinosis, and these microaneurysms then suddenly
rupture. This may also occur in malignant tumour
neovasculature, vasculitis, mycotic aneurysms, amyloidosis, sarcoidosis, malignant hypertension, primary
haemorrhagic disorders and over-anticoagulation.

Occasionally, cerebral aneurysms or AVMs may
cause intracerebral haemorrhage without SAH. Where
intracerebral haemorrhage occurs in young patients,
the most likely cause is an underlying vascular abnormality. In some areas, this is also associated with the
abuse of drugs with sympathomimetic activity, such
as cocaine. The rupture of microaneurysms tends to
occur at the bifurcation of small perforating arteries.
Common sites of haemorrhage are the putamen (55%),
cerebral cortex (15%), thalamus (10%), pons (10%) and
cerebellum (10%). Haemorrhage is usually due to the
rupture of a single vessel, and the size of the haemorrhage is influenced by the anatomical resistance of
the site into which it occurs. The effect of the haemorrhage is determined by the area of brain tissue that it
destroys. Cortical haemorrhages tend to be larger than
pontine bleeds (Fig. 51.2), but the latter are much more

Usually, there are no prodromal symptoms, and a
sudden onset of focal neurology or depressed level
of consciousness occurs. Headache and neck stiffness
will occur in conscious patients if there is subarachnoid extension by haemorrhage into the ventricles.
Where intraventricular extension occurs there may be
a progressive fall in GCS as secondary hydrocephalus occurs, and this may be accompanied by ocular
palsies, resulting in ‘sunset eyes’. Early deterioration
is common in the first few hours after haemorrhagic
stroke and more than 20% of patients will drop their
GCS by two or more points between the initial onset
of symptoms and arrival in the emergency department.14 As with ischaemic stroke, focal neurology is
determined by which area of the brain is involved. The
only way to differentiate absolutely between ischaemic, intracerebral and SAH is by appropriate imaging.
The symptoms relate to tissue destruction, compression and raised ICP, which, if progressive, will result
in brainstem ischaemia and death.

destructive owing to the anatomical density of neural
tracts and nuclei.

INVESTIGATIONS
The general investigations are essentially those listed
previously for ischaemic stroke, since it is difficult


656

Acute cerebrovascular complications

to distinguish between the two in the early stages.
Patients undergoing treatment with oral anticoagulants, particularly warfarin in atrial fibrillation, mean
that anticoagulant-associated ICH is increasing in frequency and a full coagulation screen is essential.14 CT
and/or MRI should be performed at the earliest opportunity. The early deterioration seen in ICH relates to
active bleeding and repeat imaging after 3 hours of
symptom onset often shows significant enlargement
of the initial haematoma. CTA/MRA or venography is very important to determine the cause of the
haemorrhage such as AVM, aneurysm or tumour neovasculature. Lumbar puncture may be performed to
exclude infection if mycotic aneurysm is suspected,
but only after CT has excluded raised ICP or noncommunicating hydrocephalus.
MANAGEMENT
The general management principles are identical to
those for ischaemic stroke. There is, of course, no place
for anticoagulation or thrombolysis, and reversal of
any coagulation defect, either primary or secondary
to therapeutic anticoagulation, must be undertaken as
a matter of urgency. A full coagulation screen must

be performed and the administration of vitamin K,
fresh frozen plasma, cryoprecipitate, etc., directed by
the results. Where emergency decompressive surgery
is indicated, warfarin-induced coagulopathy should
be corrected using prothrombin complex concentrate
(Beriplex or Octaplex). Intraventricular extension
occurs in around 45% of cases and the insertion of an
EVD may increase the conscious level, particularly in
the presence of secondary hydrocephalus. The EVD
level should be set so that the cerebrospinal fluid (CSF)
drains at around 10 mm Hg. The normal production of
CSF should produce an hourly output and a sudden
fall in output to zero should alert staff to the possibility
that the drain has blocked. This is particularly likely
if the CSF is heavily blood-stained. The meniscus of
the CSF within the drain tubing should be examined
for transmitted vascular pulsation or the level of the
drain temporally lowered by a few centimetres to see
if drainage occurs. If the drain is blocked, secondary
hydrocephalus will recur. Because of the risk of introducing infection and causing ventriculitis, the drain
must be unblocked in a sterile manner by the neurosurgeons. Blood in the CSF acts as a pyrogen, but the
patient’s high temperature should never be ascribed
to this alone, and regular blood cultures and CSF
samples are required as part of sepsis surveillance.
Operative decompression of the haematoma should
be undertaken only in neurosurgical centres, and safe
transfer must be assured if this is considered. The
administration of mannitol prior to transfer should be
discussed with the neurosurgical unit. There is some
evidence that patients with supratentorial intracerebral

haemorrhage less than 1 cm from the cortical surface

benefitted from surgery within 96 hours, although
this finding did not reach statistical significance. 15
Current recommendations of the American Heart
Association/American Stroke Association (AHA/
ASA) are: ‘Patients with cerebellar hemorrhage who
are deteriorating neurologically or who have brainstem compression and/or hydrocephalus from ventricular obstruction should undergo surgical removal
of the hemorrhage as soon as possible’.14 The management of hypertension following spontaneous intracerebral haemorrhage may be difficult as too high a BP
may provoke further bleeding, whereas too low a BP
may result in ischaemia. Current recommendations of
the AHA/ASA are: ‘ICH patients presenting with SBP
between 150 and 220 mm Hg and without contraindication to acute BP treatment, acute lowering of SBP to
140 mm Hg is safe and can be effective for improving
functional outcome’.14 This should be done for 7 days.2
The adoption of these guidelines may have significant
resource implications regarding access to ICU beds
to provide the required levels of monitoring. There is
no place for steroids, and hyperventilation to PaCO 2
of 30 mm Hg (4 kPa) or less to control raised ICP will
have detrimental effects on cerebral blood flow in
other areas of the brain.
SUBARACHNOID HAEMORRHAGE
SAH refers to bleeding that occurs principally into the
subarachnoid space and not into the brain parenchyma.
The incidence of SAH is around 6/100,000; the apparent decrease, compared with earlier studies, is due to
more frequent use of CT scanning, which allows exclusion of other types of haemorrhage. Risk factors are
the same as for stroke, but SAH patients are usually
younger, peaking in the sixth decade, with a femaleto-male ratio of 1.24 : 1. The only modifiable risk factors
for SAH are smoking, heavy drinking, the use of sympathomimetics (e.g. cocaine) and hypertension, which

increase the risk odds ratio by 2 or 3. Overall mortality is 50%, of which 15% die before reaching hospital,
with up to 30% of survivors having residual deficitproducing dependency. High-volume centres (>60
cases per year) have shown a much improved outcome
over that of low-volume centres (<20 cases per year).16
AETIOLOGY AND PATHOLOGY
The majority of cases of SAH are caused by ruptured
saccular (berry) aneurysms (85%), the remainder being
caused by non-aneurysmal perimesencephalic haemorrhage (10%) and rarer causes, such as arterial dissection, cerebral or dural AVMs, mycotic aneurysm,
pituitary apoplexy, vascular lesions at the top of the
spinal cord and cocaine abuse. Saccular aneurysms
are not congenital, almost never occur in neonates and
young children and develop during later life. It is not


Subarachnoid haemorrhage
known why some adults develop aneurysms at arterial
bifurcations in the circle of Willis and some do not. It
was thought that there was a congenital weakness in
the tunica media, but gaps in the arterial muscle wall
are equally as common in patients with or without
aneurysms and, once the aneurysm is formed, the
weakness is found in the wall of the sac and not at its
neck.17 The association with smoking, hypertension
and heavy drinking would suggest that degenerative
processes are involved. Sudden hypertension plays a
role in causing rupture, as shown by SAH in patients
taking crack cocaine or, rarely, high doses of decongestants, such as pseudoephedrine.

Table 51.2  C
 linical neurological classification of

subarachnoid haemorrhage
GRADE

SIGNS

I

Conscious patient with or without meningism

II

Drowsy patient with no significant
neurological deficit

III

Drowsy patient with neurological deficit –
probably intracerebral clot

IV

Deteriorating patient with major neurological
deficit (because of large intracerebral clot)

V

Moribund patient with extensor rigidity and
failing vital centres

CLINICAL PRESENTATION

Classically, there is a ‘thunderclap’ headache developing in seconds, with half of the patients describing its
onset as instantaneous. This is followed by a period of
depressed consciousness for less than 1 hour in 50% of
patients, with focal neurology in about 30% of patients.
About one-fifth of patients recall similar headaches
and these may have been due to sentinel bleeds; this
increases the chances of early rebleed 10-fold. The
degree of depression of consciousness depends upon
the site and extent of the haemorrhage. Meningism
– neck stiffness, photophobia, vomiting and a positive Kernig’s sign – is common in those patients with
higher GCS. A high index of suspicion is needed for
patients presenting with the classical headache; a noncontrast CT is recommended and, if negative, a lumbar
puncture should be done 12 hours after ictus. If that is
also negative, consider CTA.
The clinical severity of SAH is often described by
a grade, the most widely used being that described
by the World Federation of Neurological Surgeons
(WFNS), which is summarised in Table 51.2. This
grading, together with the extent of the haemorrhage
and the age of the patient, gives some indication of the
prognosis, in that the worse the grade the bigger the
bleed, and the older the patient the less likely is a good
prognosis. Another scale [Prognosis on Admission
of Aneurysmal Subarachnoid Hemorrhage (PAASH)
scale] has been validated for SAH prognosis, and has
shown some benefits over WFNS; however WFNS is
currently the most used and recommended scale. 18
Other poor prognostic signs are pre-existing severe
medical illness, clinically symptomatic vasospasm,
delayed multiple cerebral infarction, hyperglycaemia,

fever, anaemia and medical complications, such as
pneumonia and sepsis. Anatomical risk factors may
increase periprocedural risk of complications. On the
other hand, better outcomes seem to be associated with
treatment in a high-volume neurosurgical centre.
COMPLICATIONS
The clinical status of the patient may be complicated
by factors other than the physical effect of the initial

657

WFNS GRADE

GCS

MOTOR DEFICIT

I

15

Absent

II

14–13

Absent

III

14–13

Present

IV

12–7

Present or absent

V

3–6

Present or absent

GCS, Glasgow Coma Score; WFNS, World Federation of Neurological
Surgeons.

bleed. Factors, such as acute hydrocephalus, early
rebleeding, cerebral vasospasm, parenchymal haematoma, seizures and medical complications, must be
considered.
REBLEEDING
This may occur within the first few hours after admission and 15% of patients may deteriorate from their
admission status. They may require urgent intubation
and resuscitation, but not all rebleeds are unsurvivable, and as such deterioration should be treated. The
chance of rebleeding is dependent on the site of the
aneurysm, the presence of the clot, the degree of vasospasm and the age and sex of the patient. Although most
studies quote an incidence for rebleeding of 4% in the

first 24 hours, more recent studies suggest an incidence
of 9%–17% with most cases occurring within 6 hours.
A few small studies have shown that antifibrinolytics,
such as tranexamic acid, can be used early and short
term (<72 hours) in patients who do not have a preexisting high risk for thrombotic events, for the prevention of rebleeding while awaiting securing of the
aneurysm. It is an off-licence use of antifibrinolytics.16
ACUTE HYDROCEPHALUS
This may occur within the first 24 hours post ictus and
is often characterised by a drop in the GCS, sluggish
pupillary responses and bilateral downward deviation of the eyes (‘sunset eyes’). If these signs occur, a
CT scan should be repeated and, if hydrocephalus is


658

Acute cerebrovascular complications

confirmed or there is a large amount of intraventricular
blood, then a ventricular drain may be inserted. This is
recommended by the AHA/ASA.19
DELAYED CEREBRAL ISCHAEMIA
Vasospasm is the term used to describe the narrowing of the cerebral blood vessels in response to the
SAH seen on angiography. It occurs in up to 70% of
patients, but not all of these patients will have symptoms. Delayed cerebral ischaemia (DCI) refers to the
onset of focal neurological deficit, a drop in GCS by 2
or more points, and/or cerebral infarction that occurs
typically 4–12 days post SAH unrelated to aneurysm
treatment or other causes of neurological deficit, such
as hydrocephalus, cerebral oedema or metabolic disorder.20 The use of transcranial Doppler (TCD) to estimate middle cerebral artery blood velocity has shown
that a velocity of more than 120 cm/s correlates with

angiographic evidence of vasospasm. This technology
allows diagnosis in the ICU and provides a means of
monitoring the success of treatment to reduce DCI,
which is undertaken to reduce the severity of delayed
neurological deficit secondary to vasospasm. The
problem is that not all patients who have angiographic
vasospasm or high Doppler velocities have symptoms.
If there is evidence of a depressed level of consciousness in the absence of rebleeding, hydrocephalus or
metabolic disturbances, but there is evidence of DCI
clinically, on TCD or angiogram, then it would seem
appropriate to initiate treatment. If vasospasm occurs
at the time of angiography or coiling, then intravascular vasodilators, such as papaverine or nimodipine
have been used. CTA is the imaging modality of choice
unless intracerebral therapy is planned, then digital
subtraction angiography (DSA) is recommended as
first-line imaging.

Table 51.3  T ypes of medical complication seen in patients
with subarachnoid haemorrhage
MEDICAL COMPLICATION

INCIDENCE (%)

Arrhythmias

35

Liver dysfunction

24

Neurogenic pulmonary oedema

23

Pneumonia

22

ARDS and atelectasis

20

Renal dysfunction

5

ARDS, Acute respiratory distress syndrome.

PARENCHYMAL HAEMATOMA
This may occur in up to 30% of SAH following aneurysm rupture and has a much worse prognosis than
SAH alone. If there is mass effect with compressive
symptoms then evacuation of haematoma and simultaneous clipping of the aneurysm may improve outcome.
MEDICAL COMPLICATIONS
Medical complications will occur in 40% of SAH
patients. The mortality due to medical complications
is almost the same as that due to the combined effects
of the initial bleed, rebleeds and DCI. The types of
medical complication seen are shown in Table 51.3.
INVESTIGATIONS

The general investigations for stroke should be performed, and early CT imaging is mandatory. Blood
appears characteristically hyperdense on CT and the
pattern of haemorrhage may enable localisation of the

Figure 51.3  Subarachnoid haemorrhage on computed
tomography scan of the head.

arterial territory involved (Fig. 51.3). Very rarely, a
false-positive diagnosis may be made if there is severe
generalised oedema resulting in venous congestion in
the subarachnoid space. Small amounts of blood may
not be detected, and the incidence of false-negative
reports is around 2%.19 It may be difficult to distinguish
between post-traumatic SAH and primary aneurysmal
SAH, which precipitates a fall in the level of consciousness that provokes an accident or fall. MR scanning is
particularly effective for localising the bleed after 48


Subarachnoid haemorrhage
hours when extravasated blood is denatured, and provides a good signal on MRI.
Lumbar puncture is still necessary in those patients
where the suspicion of SAH is high despite a negative
CT, or there is a need to exclude infection. There must
be no raised ICP and at least 12 hours should have
passed to give time for the blood in the CSF to lyse,
enabling xanthochromia to develop.
Angiography via arterial catheterisation is still the
most commonly used investigation for localising
the aneurysm or other vascular abnormality prior to
surgery. It is generally performed on patients who

remain, or become, conscious after SAH. It is not
without risk and aneurysms may rupture during the
procedure, and a meta-analysis has shown a complication rate of 1.8%. Other methods under investigation
include CTA and MRA. DSA is the diagnostic tool of
choice in cases where CTA is still inconclusive.19
ICP monitoring is of limited use in SAH patients
except in those where hydrocephalus or parenchymal
haematoma is present, and early detection of pressure
increases may be the trigger for drainage or decompressive surgery.21
Multimodal monitoring: TCD studies may be useful
in detecting vasospasm or those patients in whom
autoregulation is impaired.19 The technique is dependent on there being a ‘window’ of thin temporal bone
allowing insonation of the Doppler signal along the
middle cerebral artery. It is very user dependent and
15% of patients do not have an adequate bone window.
Continuous EEG monitoring, cerebral blood flow monitoring, jugular venous oximetry, brain tissue oxygen
oximetry and cerebral microdialysis have all been used
to diagnose DCI.22
MANAGEMENT
The initial management of SAH is influenced by the
grading, medical co-morbidity or complications, and
the timing or need for surgery. Patients with decreased
GCS may need early intubation and ventilation, simply
for airway protection, whereas those with less severe
symptoms require regular neurological observation,
analgesia for headache and bed rest prior to investigation and surgery. Other management options are stress
ulcer prophylaxis, deep-vein thrombosis prophylaxis
using compression stockings or boots, and seizure
control with phenytoin or barbiturates. If the patient
is sedated and ventilated, the use of an analysing cerebral function monitor should be considered to detect

subclinical seizure activity.
Hyponatraemia is a common finding and adequate
fluid therapy with normal saline is required with
electrolyte levels maintained in the normal range.
Occasionally, as in other types of brain injury, excessive natriuresis occurs and may result in hyponatraemic dehydration – cerebral salt-wasting syndrome

659

(CSWS). 23 Its aetiology is not known, but some
suggest increased levels of atrial natriuretic peptide.
It usually occurs within the first week after insult
and resolves spontaneously in 2–4 weeks. Failure to
distinguish CSWS from the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) could
lead to inappropriate treatment by fluid restriction,
which would have adverse effects on cerebral perfusion. Urine sodium concentrations are usually elevated in both SIADH and CSWS (>40 mmol/L) but
urinary sodium excretion, urine sodium concentration [Na mmol/L] × urine volume [L/24 hours] is
high in CSWS and normal in SIADH. If CSWS does
not respond to fluid replacement with saline or is
not self-limiting then fludrocortisone therapy may be
useful. Euvolaemia is crucial to help prevent and not
exacerbate DCI.
BLOOD PRESSURE CONTROL
Elevation of BP is commonly seen after SAH and there
are no precise data on what constitutes an unacceptably high pressure that is likely to cause rebleeding.
Equally, there are no precise data on a minimum level
of pressure below which infarction is likely to occur,
since this will depend on the patient’s normal pressure, the degree of cerebral oedema and the presence
or absence of intact autoregulation. One observational study has demonstrated reduced rebleeding,
but higher rates of infarction, in newly treated compared with untreated post-SAH hypertensive patients.
Although there are no precise data on specific BP controls, the AHA guidelines recommend that systolic

BP is kept <160 mm Hg or mean arterial pressure of
<110 mm Hg in a person with an unsecured aneurysmal SAH.19 Beta-adrenergic blockers or calcium antagonists are the most widely used agents, since drugs
producing cerebral vasodilation may increase ICP.
The choice is less important than the titratability of
the drug, as the balance between the increased risk of
rebleed and cerebral perfusion needs to be maintained.
If nimodipine causes severe hypotension, timing and
dose need to be changed too (i.e. 30 mg 2-hourly
instead of 60 mg 4-hourly). If nimodipine still remains
a problem, consider omitting doses until the patient
is more cardiovascularly stable while maintaining
euvolaemia.
DELAYED CEREBRAL ISCHAEMIA
Angiographic demonstration of vasospasm may be
seen in about 70% of SAH patients, but only about
30% develop cerebral symptoms related to vasospasm,
hence the change of nomenclature.
Symptoms tend to occur between 4 and 14 days
post-bleed, which is the period when cerebral blood
flow is decreased after SAH.


660

Acute cerebrovascular complications

PREVENTION
One method of pre-empting vasospasm is oral nimodipine at 60 mg given 4-hourly for 21 days, which has
been shown to achieve a reduction in the risk of ischaemic stroke of 34%. Intravenous nimodipine should be
used in the patients who are not absorbing enterally,

but it must be titrated against BP to avoid hypotension. Aspirin, clazosentan, enoxaparin, erythropoietin,
fludrocortisone, magnesium, methylprednisolone,
nicardipine and statins have been in trials but have not
been shown to prevent DCI.22
TREATMENT
Low cerebral blood flow is known to worsen outcome
and this resulted in the development of prophylactic
hypertensive hypervolaemic haemodilution – so-called
triple-H therapy. This has been shown to cause harm.
The focus now is on euvolaemia and, if this is indicated and the BP is not already raised, hypertension
is induced with vasopressors. This needs to be done
in a stepwise fashion with assessment of neurological
function at each step.22 Cerebral angioplasty or direct
intracerebral vasodilators should be considered if
induced hypertension is not reversing the DCI symptoms. Where symptoms develop it is important to
exclude other causes, such as rebleeding, hydrocephalus or metabolic disorder. Poor-grade SAH patients
who are sedated or have low GCS are clinically difficult to assess; multimodal monitoring is recommended
to look for deterioration.22
SEIZURES
Seizure occurs in up to 26% of SAH sufferers. The
evidence for prophylactic use of anticonvulsants is
poor and not recommended. Some prognostic indicators for the development of seizures have been identified: increased intracerebral blood, poor-grade SAH,
rebleeding infarction and MCA aneurysm. Patients
should be observed for seizure activity and treated
appropriately. A patient with poor-grade SAH who
is not improving or is deteriorating neurologically,
from an unknown cause, should have continuous EEG
monitoring.16
SURGERY
Clipping of the aneurysm is the surgical treatment of

choice, with wrapping, proximal ligation or bypass
grafting being used if the aneurysm is inaccessible
to Yasargil clipping. The timing of surgery remains
debatable. Recommendations by the AHA are to
secure the aneurysm within 48 hours of ictus or 48
hours of presentation. Large intracerebral haematomas
associated with the SAH and middle cerebral artery
aneurysms should be strongly considered for surgery.
There is no good level-one evidence for the use of
induced hypertension or hypothermia during clipping,
but in certain patients it could be considered. What is

clear is that hypotension and hyperglycaemia should
be avoided.19
ENDOVASCULAR COILING
In patients with ruptured intracranial aneurysms suitable for both surgery and endovascular coiling treatments, endovascular coiling is more likely to result in
independent survival at 1 year than neurosurgical clipping; the survival benefit continues for at least 7 years.
The risk of late rebleeding is low, but is more common
after endovascular coiling than after neurosurgical
clipping as well as retreatment of up to 20%.24 Additional complications of coiling include rupture during
catheter placement in the aneurysm, coil embolisation
and vasospasm. Not all aneurysms, particularly those
with wide necks, multiple filling vessels or giant aneurysms, are suitable for coiling. Aneurysms that are
amenable to either surgery or coiling should be coiled;
if patients are elderly (>70 years) or have poor-grade
SAH then coiling is preferred. Stenting of acute SAH
carries a worse prognosis.19
THERAPY OF MEDICAL COMPLICATIONS
This is specific to the type of complication. Pneumonia may require continuous positive airway pressure
or ventilatory support together with directed antimicrobial therapy; acute respiratory distress syndrome

requires lung-protective/recruitment ventilatory
strategies; and renal failure necessitates an appropriate means of renal replacement therapy. Arrhythmias
require correction of trigger factors, such as hypovolaemia and electrolyte or acid-base disturbances prior to
the appropriate antiarrhythmic drug or direct current
cardioversion. Cardiac function should be evaluated in
patients with cardiovascular deterioration, by means
of serial enzymes and echocardiography. Cardiac
output monitoring should be considered. Neurogenic
pulmonary oedema may be associated with severe cardiogenic shock, which may require inotropic support
or even temporary intra-aortic balloon counterpulsation. The cardiogenic shock is reversible and patients
can make a good recovery despite the need for aggressive support.25
Hyper- and hyponatraemia are frequently seen, with
hyponatraemia occurring in up to 30% of cases, and it
is implicated in the development of DCI. The aim is for
euvolaemia; if it cannot be achieved because of a persistent negative fluid balance as a result of CSWS, then
fludrocortisone should be considered. Hyponatraemia
should be corrected by no more than 0.5 mmol/L per
hour with a maximum of 8 mmol/L per day (if it is
chronic; i.e. of more than 48 hours’ duration) during
which 4-hourly sodium levels should be taken. This
may be achieved by using intravenous fluid that has
more sodium than the serum concentration of the
patient. In patients who are resistant to vasopressors,
hypothalamic dysfunction should be considered and


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Blood glucose should be kept at 4.4–11.1 mmol/L

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Fever should be controlled by antipyretics as the
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Cooling devices should be considered if first-line
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52 
Cerebral protection
Colin Andrew Eynon

‘The chief function of the body is to carry the brain
around.’

such as cardiac arrest, severe sepsis or following major
trauma (Fig. 52.1).

‘The human brain has 100 billion neurons, each
neuron connected to 10 thousand other neurons.
Sitting on your shoulders is the most complicated
object in the known universe.’

CEREBRAL PERFUSION

Thomas A. Edison

Michio Kaku

CEREBRAL PHYSIOLOGY AND ANATOMY
The brain receives around 15% of the cardiac output
(50 mL/100 g/min) and utilises around 3–5 mL O2/
min per 100 g tissue and 5 mg glucose/min per 100 g
tissue. The grey matter of the brain, which consists primarily of the neuronal cell bodies and synapses, has
a higher blood flow compared with the white matter,
which consists largely of fibre tracts. Critical cerebral
blood flow (CBF) is around 20 mL/100 g/min, with
the electroencephalogram (EEG) becoming isoelectric
at 15 mL/100 g/min.
The anterior cerebral circulation is provided by the
two internal carotid arteries which subdivide into the
anterior and middle cerebral arteries. These provide
around 70% of the cerebral circulation supplying the
frontal, parietal and temporal lobes and the anterior
diencephalon (basal ganglia and hypothalamus). The
two vertebral arteries join to form the basilar artery
which supplies the posterior circulation; the brainstem, cerebellum, occipital lobes and the posterior
diencephalon (thalamus). The two circulations (anterior and posterior) are joined by communicating arteries to form the circle of Willis at the base of the brain.
As the circle facilitates collateral flow, obstruction to
one of the four principle arteries (right and left internal carotid, right and left vertebral) supplying the
brain may be clinically insignificant. Damage to the
intracerebral vessels, however, often results in significant damage due to the lack of anatomical reserve. The

areas between those supplied by the principle cerebral
arteries are supplied by the leptomeningeal arteries.
These areas are potential watershed areas that are
particularly at risk in conditions of low- or no-flow

Cerebral perfusion is controlled in part by the perfusion pressure across the brain (cerebral perfusion
pressure or CPP). CPP is the difference between the
cerebral arterial pressure and cerebral venous pressure. As these pressures are difficult to measure, systemic mean arterial pressure (MAP) and intracranial
pressure (ICP) are used as surrogates.
CPP = MAP − ICP
MAP can be estimated as equal to diastolic blood
pressure + 1/3 pulse pressure. In adults, the normal
resting ICP is 0–10 mm Hg. ICP can rise to 50 mm
Hg or higher during straining or sneezing with no
impairment in cerebral function. It is not, therefore,
an elevated ICP alone that is important in pathological conditions. CPP is around 60 mm Hg in the
normal state.
CEREBRAL METABOLISM
The energy requirements of the brain are large, in
order to maintain membrane integrity and to support
the transmembrane ion gradients required for electrical activity and cell survival. Energy is also required
for the synthesis, storage and release of neurotransmitters. Neurones produce adenosine triphosphate
almost entirely by the oxidative metabolism of glucose
and ketone bodies. Over 85% of the glucose used by
the brain undergoes oxidative metabolism with brain
tissue having only very limited ability for anaerobic
metabolism. Consciousness is lost rapidly if the supply
of either oxygen or glucose is restricted. Loss of consciousness will occur in less than 10 seconds following
acute decompression at 50,000 ft, with the time delay
resulting from the transit time of deoxygenated blood

from the lungs to the brain.1 Similarly, unconsciousness occurs swiftly following intravenous administration of high doses of insulin.2


Abstract and keywords 663.e1
ABSTRACT

KEYWORDS

The brain is arguably the most important organ in the
body and also one of its most vulnerable. Primary brain
injury may result from conditions such as trauma,
stroke or intracerebral haemorrhage (ICH), or it may
be secondarily injured most commonly due to circulatory or respiratory disease. Cerebral protection is the
application of often simple, therapeutic interventions
with the intention of limiting or preventing further
neuronal injury and thus improving the patient’s
ultimate neurological outcome. The key to cerebral
protection is early intervention, as neuronal damage
can occur within minutes of an insult. Prevention of
hypoxia, hyper- and hypocarbia, hyper- and hypoglycaemia, seizures and maintenance of adequate cerebral
perfusion and osmolarity are all important. Although
many therapeutic agents have been studied to try and
reduce neuronal damage, very few have been successfully transferred into clinical practice.

Secondary insults
intracranial pressure
cerebral perfusion pressure
time-critical
specialist care

664

Cerebral protection

Cortical border zone
(between ACA and MCA)

Internal border zone
(between LPA and MCA)

Cortical border zone
(between MCA and PCA)

Figure 52.1  Axial view of the brain showing the major arterial territories. Watershed infarcts may occur at the border
between the major cerebral arterial territories in conditions of low blood flow. These may be (a) cortical border zone
infarcts (infarction of the cortex and neighbouring subcortical white matter at the border of the ACA and the MCA and/or
the MCA and the PCA), or (b) internal border zone infarction of deep white matter (between the LPA and the deep cortical
branches of the MCA or at the border zone of deep white matter branches of the MCA and the ACA). ACA, Anterior
cerebral artery; LPA, lentriculostriate perforating arteries; MCA, middle cerebral artery; PCA, posterior cerebral artery.

LOCAL CONTROL OF CEREBRAL BLOOD FLOW
AUTOREGULATION (MYOGENIC REGULATION)

100
CBF (mL/100 g/min)

Autoregulation ensures that CBF remains constant
between MAPs from 60 to 160 mm Hg. The stimulus
for autoregulation is CPP. Autoregulation is thought to

be a myogenic mechanism with reflex vasoconstriction
of cerebral vessels occurring in response to increases
in CPP and vascular wall tension, and vasodilatation
occurring in response to decreases in CPP and reduction in wall tension.3 Outside the values where autoregulation is effective, the relationship between CBF and
MAP is linear and CBF is pressure dependent (Fig.
52.2). The range at which autoregulation can operate
varies with age and in certain pathological conditions.
The range is shifted to the left in early life and to the
right in chronic hypertension. A rapid reduction in the
blood pressure of a patient with chronic hypertension
risks inadequate perfusion of the brain, heart and/or
the kidneys. Autoregulation may be also impaired by
hypoxia, ischaemia, hypercapnia, trauma and certain
anaesthetic agents.
Rapid rises in systemic blood pressure are also
poorly tolerated. Hypertensive emergencies occur
in an estimated 1–2/100,000 patients per year and
may be associated with retinopathy, papilloedema or
encephalopathy. Hypertensive encephalopathy results
from cerebral oedema due to increased hydrostatic
pressures and can cause drowsiness, coma, seizures

50

0

0

50

100
MAP (mm Hg)

150

Figure 52.2  The relationship between mean arterial
pressure (MAP) and cerebral blood flow (CBF)
under normal circumstances, illustrating the range of
autoregulation.

and ICH. Posterior reversible encephalopathy syndrome (PRES) may present with seizures, disturbed
vision, headache and altered mental state. 4 It is
strongly linked to conditions that co-exist in patients
with renal disease, such as hypertension, vascular
and autoimmune diseases, immunosuppression, and
organ transplantation. More than 70% of patients are


Cerebral injury

665

100
Pco2

100
CBF (mL/100 g/min)

CBF
mL/100 g/min

75

50

Po2
50

25
0
2

3.3 4
CMRO2
mL/100 g/min

0

hypertensive. Typical magnetic resonance imaging
(MRI) findings are of reversible, symmetrical, posterior subcortical vasogenic oedema.5 If promptly treated
and managed, symptoms often resolve within a few
days to weeks.
FLOW–METABOLISM COUPLING
Flow–metabolism coupling is the direct relationship
of the metabolic activity of the brain to CBF. Increases
in metabolic demand are met rapidly by increases in
CBF and delivery of substrates (Fig. 52.3). The exact
mechanisms that control flow–metabolism coupling
are unknown but may involve a variety of mediators
such as neurokinin-A, nitric oxide and substance P. It is

not clear how the diameter of cerebral vessels upstream
to the area of activity can be altered so rapidly by metabolic products which are being washed downstream. It
is thought that there may be control neurons that act on
specific cerebral vessels that control local blood flow.6
Regional variations in cerebral metabolism can now be
visualised using techniques such as positron emission
tomography scanning, although the hypothesis that
such variations existed dates as far back as 1890.7
SYSTEMIC CONTROL OF CEREBRAL  
BLOOD FLOW
CARBON DIOXIDE
CBF increases by 3%–4% for each mm Hg increase in
PaCO 2 . A doubling of PaCO 2 doubles CBF and conversely a halving of PaCO 2 will halve CBF (Fig. 52.4).
The responses to changes in PaCO 2 occur rapidly,
within 30s, and are thought to relate to changes in

10
50

6

Figure 52.3  Flow-metabolism coupling. As the cerebral
metabolic rate for oxygen (CMRO2) increases there
is proportional increase in cerebral blood flow (CBF).
Normal CBF is around 50 mL/100 g/min.

5
Po2

Pco2

15
100

(kPa)
150 (mm Hg)

Figure 52.4  The relationship between the partial pressure
of oxygen and carbon dioxide and cerebral blood flow
(CBF).

extracellular or interstitial hydrogen ion concentrations. Tight control of PaCO 2 is essential if CPP is critical; increases in CO2 cause vasodilatation and increased
ICP, whereas decreases in PaCO 2 below 4 kPa have
been shown to result in vasoconstriction sufficient to
precipitate critical cerebral ischaemia.8 Impaired CO2
reactivity is associated with poor outcomes in patients
with severe head injury.9
OXYGEN
CBF is not affected by changes in Pa O2 within the
normal range, but levels <50 mm Hg (6.65 kPa) result
in cerebral vasodilatation and increases in CBF. Below
30 mm Hg (4 kPa), CBF is roughly doubled with a consequent increase in ICP (see Fig. 52.4).
TEMPERATURE
The cerebral metabolic rate for oxygen (CMRO2) is
reduced by around 8% for each degree Celsius reduction in temperature. Mild hypothermia remains recommended for the management of patients who are
resuscitated from cardiac arrest. 10 More profound
cooling enables patients to withstand prolonged
periods of low CBF during cardiopulmonary bypass.
Application of cooling to unselected patients with traumatic brain injury is now thought to be ineffective.11
Avoidance of hyperthermia in cerebral injury remains

important as CMRO2 is increased by a similar amount
for every degree Celsius increase in temperature.
CEREBRAL INJURY
Cerebral injury is commonly divided into primary
and secondary. Primary injuries include traumatic,


666

Cerebral protection

ischaemic or hypoxic and may be focal or global. Secondary injuries may be initiated as a consequence of
the primary injury and can contribute significantly to
the ultimate outcome of the patient.
Primary traumatic brain injury may result in four
main pathological conditions which can all co-exist:
brain contusions, axial and extra-axial haematomas
(subdural, extradural and intracerebral), traumatic
subarachnoid haemorrhage (SAH) and diffuse axonal
injury (DAI). DAI results from dynamic deformation
of the brain with resultant shearing forces, affecting
the blood vessels and axons. Areas commonly affected
include axons in the brainstem, the parasagittal
white matter near the cerebral cortex, and the corpus
callosum.12
Focal hypoxic or ischaemic insults often occur
acutely such as in acute stroke. If the area supplied by
the affected artery has a good collateral supply, injury
may be modest. If, however, the area is poorly supplied,
cell death will occur within minutes without reperfusion. Around areas of infarction there is an ischaemic

penumbra. Interventions to preserve function in the
penumbral area are the key to optimising outcome.
Global hypoxic-ischaemic conditions are often secondary to respiratory or cardiovascular insufficiency,
seen most severely in cardiorespiratory arrest. Recovery depends on rapid reversal of the primary cause.
MRI examination of patients with persistent disorders
of consciousness following resuscitation from cardiac
arrest have shown regions of pathological white
matter signals in the frontal and occipital lobes and
in the periventricular regions.13 The total volumes of
the lesions have been associated with the severity of
the patients’ outcomes. These patterns demonstrate the
different vulnerabilities of particular areas of the brain
to ischaemia-hypoxia.
Secondary injury may be initiated as a consequence
of the primary injury. The duration and severity of secondary insults can have a significant effect on patient
outcome and present an opportunity for prevention
or early clinical intervention.14–17 Intracranial secondary injury may be caused by expansion of intracranial
haematomas or the development of cerebral oedema
causing pressure effects on more distant parts of the
brain, distortion of blood supply or further axonal
shearing. Shift of vital structures can ultimately lead to
herniation of the brain. Secondary seizure activity can
rapidly deplete the brain’s supply of metabolites.
Systemic secondary insults include hypoxia,
hypotension, hyper- or hypocarbia, hyperthermia,
hyper- and hypoglycaemia, anaemia and electrolyte
disturbances. Many studies have demonstrated the
importance of the duration and severity of secondary
insults on the outcome from traumatic brain injury
(Table 52.1).

Although hyperventilation of patients with severe
brain injury has previously been recommended as a
short-term measure to manage elevated ICP before

Table 52.1  E
 ffects of secondary injuries on outcome from
traumatic brain injury

INSULT

IMPACT
ON
MORTALITY

IMPACT ON
GLASGOW
OUTCOME
SCORE

Duration of SBP <90 mm Hg

Yes

Yes

Duration of SaO2 <90%

Yes

No

Duration of temp >38°C

Yes

No

Duration of ICP >30 mm Hg

Yes

No

Duration of CPP <50 mm Hg

Yes

No

CPP, cerebral perfusion pressure; ICP, intracranial pressure; SBP, systolic
blood pressure.

more definitive measures can be employed, there is
now evidence of the effects of hypocarbia on cerebral
vasculature with vasoconstriction and secondary
ischaemia/hypoxia. Levels of PaCO 2 below 4 kpa
should be avoided.8
Anaemia has been associated with poorer outcomes
in traumatic brain injury (TBI), aneurysmal SAH, ICH
and ischaemic stroke. Transfusion improves brain oxygenation in some patients with TBI.18 Most critical care

units now adopt a restrictive strategy to red cell transfusion using a trigger haemoglobin around 7–8 g/dL.
In patients with TBI, neither administration of erythropoietin nor maintaining a haemoglobin concentration
>10 g/dL have resulted in improvement in neurological outcome and the 10 g/dL threshold was associated
with a greater incidence of adverse events.19
The brain is particularly vulnerable to disturbances
of osmolality.20,21 Under physiological conditions, brain
osmolality is in equilibrium with extracellular fluid
osmolality. When hyponatraemia occurs, the reduction in plasma osmolality causes water movement into
the brain along the osmotic gradient, causing cerebral
oedema. Cerebral volume increases by around 7% for
every three milli-osmolar reduction in osmolality.
METABOLIC AND BIOCHEMICAL PROCESSES  
IN CEREBRAL INJURY
The pathophysiology of brain injury is complex (Fig.
52.5). Even brief disturbances in CBF and delivery of
substrates can initiate a cascade of events leading to
cellular death.22 Different areas of brain have differing thresholds for damage, with the cell bodies (grey
matter) being more resilient than the white matter
(axons). Anaerobic metabolism results in intracerebral
acidosis with accumulation of lactic acid and hydrogen ions. Loss of the normal homeostatic mechanisms
responsible for the maintenance of ion gradients results
in abnormal sodium, potassium, calcium and chloride
movements and the failure of glutamate reuptake into


Cerebral protective strategies

667

Brain Injury

focal, diffuse, rotational, penetrating and shearing
Systemic Impact

PRIMARY
INJURY

Time

seconds to
minutes

SECONDARY INJURY

hours
to days

weeks to
months

months
to years

Vascular Compromise/
Haemorrhage
• critical nutrient compromise
• iron release

Diffuse Axonal Injury
(DAI)
• axonal stretching and

tearing (acute)
• synapse loss

Ischaemia
Swelling/Oedema
• direct vascular
• decreased cerebral
injury leads to
blood flow via vascular
decreased cerebral compression
blood flow

Cellular Injury
• Depolarisation
• calcium influx
• glutamate release
• oxidative stress
• mitochondrial dysfunction

Inflammation
• contributes to oedema
• induces apoptosis (chronic)

Neuroplasticity
• remodelling
• directly related to mental
and physical health

Neuroplasticity

Local Impact

Cellular Dysfunction
• neuronal cell loss (acute)
• axonal degeneration

Cell Death/Apoptosis
• induced apoptosis
• axonal degeneration
• hormonal dysfunction

Neurological/Behavioral
Compromise
• neurocognitive dysfunction

Hypothalamic-Pituitary
Deficiencies
• hormonal dysfunction

Figure 52.5  Hypothesised model for progression from primary to secondary injury after trauma to the central nervous
system. Modified from Reifschneider K, Auble BA, Rose SR. Update of endocrine dysfunction following paediatric
traumatic brain injury. J Clin Med. 2015;4(8):1536–1560 (with permission).

cells. Glutamate and aspartate are the main excitatory
neurotransmitters in the brain. When uptake mechanisms fail, toxic levels of glutamate can accumulate
in the extracellular space, causing a surge of neuronal
activity and membrane depolarisation. The increases
in intracellular calcium and sodium activate pathways
mediated by Ca2+ dependent enzymes. The restriction
of oxygen and substrates to mitochondria induces a

cellular metabolic crisis with disruption of cell membranes and organelles, activation of cellular apoptosis,
activation of macrophages and platelet aggregation
causing secondary disturbances of the microvasculature. Cytotoxic oedema occurs due to failure of ionic
pumps with subsequent ion and fluid shifts. Vasogenic oedema is due to mediator release with damage
to endothelium, basement membranes and glial cells
with breakdown of the blood-brain barrier.
CEREBRAL PROTECTIVE STRATEGIES
For all patients, including those with brain injury,
the priorities are the assessment and management
of airway, breathing and circulation (ABC) over

assessment of the neurological status (D – disability).
For patients who have sustained major trauma, control
of catastrophic haemorrhage is now included before
ABC (C-ABC). Cerebral protective strategies must start
pre-hospital to maximise the opportunities for a good
neurological outcome.
AIRWAY
Recommendations regarding securing of the airway in
patients with brain injury include those patients with
the following23:

•Glasgow

Coma Score ≤8, or with a significantly
deteriorating conscious level (i.e. fall in motor score
of ≥ two points)
• Loss of protective laryngeal reflexes
• Hypoxia (PaO2 <13 kPa on oxygen)
• Hypercarbia (PaCO 2 >6 kPa)

•Spontaneous hyperventilation causing PaCO 2
<4.0 kPa
•Bilateral fractured mandible or copious bleeding
into the mouth (e.g. from skull base fracture)
•Seizures


668

Cerebral protection

The projected clinical course of the patient should
also be considered. Those requiring transfer for definitive care or who are likely to require surgery for other
conditions may require early intubation.
OXYGEN
The National Confidential Enquiry into Patient
Outcome and Death (NCEPOD) report, ‘Trauma: who
cares?’ published in 2007 found that administration of
oxygen was only documented to have occurred in 78%
of patients with neurological injury and that peripheral
oxygen saturations of <95% occurred in 28% of patients
pre-hospital.24 In mechanically ventilated patients with
TBI, avoidance of hypoxia may require application of
positive end-expiratory pressure (PEEP) especially in
patients with polytrauma. Although there is a theoretical risk that the increase in intrathoracic pressure
can cause increased cerebral blood volume (CBV) and
ICP, application of PEEP up to 15 cm H2O has been
used successfully in cases of refractory hypoxaemia.25
National Institute for Health and Clinical Excellence
(NICE) recommendations are that patients with acute

stroke should have supplemental oxygen if the peripheral oxygen saturations fall below 95%.26
CARBON DIOXIDE
Tight control of PaCO 2 is required for all mechanically
ventilated patients with acute cerebral injury. This
can create difficulties in patients with co-existent lung
disease or acute respiratory distress syndrome (ARDS)
where a balance needs to be struck between the effects
of a raised PaCO 2 on the brain and lung-protective
strategies.27–29 As detailed earlier, a target PaCO 2 of
4.5–5 kPa is usual in the acute stages of injury.
CEREBRAL PERFUSION (BLOOD  
PRESSURE TARGETS)
Cerebral perfusion depends on MAP and ICP. If the
ICP is elevated due to the presence of intracranial
haemorrhage or swelling, MAP must be increased to
maintain CPP. Many patients with isolated acute intracranial injury have an initial period of arterial hypertension. Generally this will reduce spontaneously or with
simple measures such as analgesia, relieving hypoxia
or hypercarbia, and ensuring that the patient does not
have other systemic disturbances such as urinary retention. There have been concerns that reducing the blood
pressure acutely may risk the perfusion of penumbral
areas and worsen the clinical outcome. Recent studies
have shown benefit with intensive management of
elevated blood pressure for patients with spontaneous ICH and in the early phase of management of
SAH before the aneurysm is secured.30 In patients with
acute ischaemic stroke, the blood pressure needs to be
less than 185/110 mm Hg prior to administration of

thrombolytic therapy and controlled <180/105 mm Hg
for the next 24 hours thereafter.
For patients who are unconscious following traumatic brain injury, it is generally recommended that

the MAP target should be >80 mm Hg with the presumption that ICP is at least 20 mm Hg. This can
present a challenge, especially with multiply injured
patients. A patient who is hypotensive despite resuscitation should not be transported to specialist care until
the cause has been identified and the patient stabilised.
Persistent hypotension will significantly adversely
affect the neurological outcome.
FLUIDS
Isotonic crystalloid and blood (if required) are the
mainstays of fluid replacement in patients with cerebral injury; 0.9% saline is the only isotonic crystalloid solution that is commonly available. Gelatins,
albumin, Ringer’s lactate (compound sodium lactate),
Ringer’s acetate and Plasma-Lyte should be avoided
as all are hypotonic when real osmolality (mosm/
kg) is measured. The Brain Trauma Foundation (BTF)
recommends that the sodium be kept >140 mmol/L
for patients with TBI.31 This avoids the risk of worsening cerebral oedema. Hyperosmolar therapy such as
mannitol (2 mL/kg of a 20% solution) or hypertonic
saline are often used when ICP is critically elevated.
Despite clear effectiveness on measured ICP, there
remains little evidence of improvement in clinical
outcomes.32
POSITIONING 30 DEGREE HEAD UP  
(WITH SPINAL PRECAUTIONS)
Measures such as elevating the head of the bed by 30
degrees, ensuring the head is in a neutral position and
in alignment with the body are important, simple steps
that can reduce ICP. For patients with potential spinal
injuries, the whole bed should be tilted.
TEMPERATURE CONTROL
Pyrexia is common following acute brain injury. Vigilance for possible infective sources, drug reactions or
physical causes such as venous thromboembolism is

essential. Central (neurogenic) fever can occur, thought
due to disturbance of temperature regulation in the
hypothalamus. It is uncommon and characterised by
a constant fever which is often >40°C. As the normal
regulatory point has been altered, patients characteristically have an absence of the measures normally taken
to mitigate hyperthermia, such as sweating.33 Maintenance of normothermia is common practice in specialist intensive care units (ICUs). Although therapeutic
hypothermia has been shown to reduce ICP in patients
with TBI, its widespread use has not been found to
be beneficial in clinical trials.11 Targeted temperature


Cerebral protective strategies
management remains recommended for patients
who remain unresponsive after resuscitation from
cardiac arrest.10
SEDATION/ANALGESIA
Patients requiring intubation for cerebral protection
are usually managed using a rapid sequence induction technique (with in-line stabilisation of the cervical spine for those with potential trauma). The use of
an opiate is recommended to mitigate rises in ICP.
The induction agent and dose used should be chosen
to ensure maintenance of an adequate MAP. Commonly, barbiturates or propofol are used. Ketamine
may be useful in haemodynamically unstable patients.
The concerns regarding potential increases in ICP and
cerebral metabolic rate with ketamine appear to be
clinically unfounded.34,35 Following intubation and ventilation, sedation in brain-injured patients is commonly
maintained with continuous intravenous infusions of
propofol or midazolam. Both reduce the cerebral metabolic rate for oxygen and CBF. High doses are often
required to decrease the ICP. Use of continuous infusions of an opiate may help in reducing the amount
of sedative required especially if there are concerns
regarding propofol infusion syndrome.

SEIZURE CONTROL
Risk factors for early seizures following trauma (within
7 days of injury) include: Glasgow Coma Score (GCS)
≤10; immediate seizures, post-traumatic amnesia >30
minutes, linear or depressed skull fracture, penetrating
head injury, subdural, epidural, or intracerebral haematoma, cerebral contusions, age ≤65 years, or chronic
alcoholism.31 Post-traumatic epilepsy is defined as
recurrent seizures occurring more than 7 days following injury. The BTF recommends the use of phenytoin
to decrease the incidence of early seizures when the
overall benefit is felt to outweigh the potential complications associated with treatment.31
Seizures occur at the time of bleeding in around 7%
of patients with SAH.36 Another 10% will develop seizures over the first few weeks. Risk factors for early
seizures include middle cerebral artery (MCA) aneurysm, thickness of acute subarachnoid clot, associated
ICH, re-bleeds, cerebral infarction, poor neurological grade and mode of treatment with endovascular
treatment having a lower risk of seizures.36 The European Stroke Organisation recommends antiepileptic
treatment only for those patients with overt seizures.
The American Heart Association (AHA)/American
Stroke Association guidance states that prophylactic
anticonvulsants may be considered in the immediate
post-haemorrhagic period.37 Seizures occur in <16% of
patient within 1 week after ICH. A cortical location of
the ICH is the most important risk factor for early seizures. Prophylactic anticonvulsant medication has not

669

been shown to be beneficial and the AHA recommends
only treatment of clinical seizures.38
GLUCOSE CONTROL
Hyperglycaemia has been associated with poorer outcomes for a wide range of acute neurological conditions including TBI, SAH, ICH and acute ischaemic
stroke.39 Studies of tight glycaemic control have been

disappointing and guidelines recommend the avoidance of both hyperglycaemia and hypoglycaemia.
SPECIFIC PHARMACOLOGICAL INTERVENTIONS
Although many potential neuroprotective agents have
been tried, most clinical studies have failed to show
outcome benefits.22 Nimodipine is used to prevent
cerebral vasospasm following aneurysmal SAH.40 The
lack of evidence regarding pharmacological interventions emphasises the importance of the adoption of
simple protective measures and rapid access to specialist care.
SPECIALIST MONITORING
INTRACRANIAL PRESSURE
The major intracranial contents are the brain, blood
(both arterial and venous), and cerebrospinal fluid
(CSF). When a new intracranial mass is introduced
(haemorrhage, hydrocephalus or cerebral oedema), a
compensatory change in volume must occur through
a reciprocal decrease in venous blood or CSF to maintain a constant total intracranial volume. This is the
Monro-Kellie doctrine. In young children, with open
fontanelles and whose sutures have not yet fused, the
cranium can expand to physically accommodate extra
volume. In the normal situation, changes in intracerebral volume produce little or no change in ICP and the
compensatory reserve is good. If compensatory reserve
is poor, any changes in intracerebral volume produce
a rapid rise in ICP.
Although there is a lack of Class 1 evidence to
support the measurement of ICP and the targeting of
CPP in severe head injury, there is good evidence that
measurement of these as part of a guideline of care
on specialist units results in improvements in mortality and functional outcomes following brain injury.31
Measurement of ICP may be of use in a number of
other neurological conditions. 41 The value of ICPbased management for non-traumatic conditions is

even less clear than in traumatic brain injury.
The devices commonly used to measure ICP are
intraventricular and intraparenchymal catheter tip
microtransducer catheters. Intraparenchymal monitors
are most commonly placed by making a small incision
in the scalp, screwing a bolt into the skull and then
passing a spinal needle through the lumen of the bolt,


670

Cerebral protection

puncturing the dura. The monitor is then zeroed to
atmospheric pressure before the transducer is passed
through the bolt and into the brain parenchyma. The
transducer is usually placed into the non-dominant
frontal lobe or the dominant frontal lobe if the nondominant lobe is the primary site of injury. The drift
over time of modern intraparenchymal monitors is
insignificant, the rates of infection are low and there
is no need to routinely change the monitor. Pressure
transducers in the subdural or subarachnoid space are
now rarely used.
Intraventricular catheters are the gold standard
for monitoring ICP and also allow drainage of CSF if
the ICP is raised. External ventricular devices (EVDs)
can be placed during craniotomy procedures or via a
burr hole in similar manner to the intraparenchymal
devices. If the ventricles are compressed, placement
can be facilitated using ultrasound or stereotactic

computed tomography (CT) guidance. The pressure
monitor is zeroed to the level of the external auditory meatus. The risks from EVDs include a rate of
<5% for placement-associated ICH (although the need
for neurosurgical evacuation is far smaller) and <20%
for catheter-related infections. Infection rates increase
with the duration of placement and can be reduced by
strict attention to asepsis during manipulation or use
of antibiotic or silver-impregnated catheters.
Non-invasive methods of measuring ICP include
transcranial Doppler (TCD), measurement of optic
nerve sheath diameter and tympanic membrane
displacement. Operator experience and reproducibility have limited the clinical applications of these
techniques.
INTRACRANIAL PRESSURE IN NORMAL AND
PATHOLOGICAL CONDITIONS
The normal ICP trace looks similar to an arterial trace
(Fig. 52.6A). The three peaks are: P1 – the percussion
wave caused by arterial pressure transmitted from the
choroid plexus to the ventricle; P2 – the tidal wave
thought to be due to brain compliance; and P3 – the
dicrotic wave resulting from closure of the aortic valve.
If the intracranial volume is increased, the ICP waveform shows an initial increase in amplitude, although
the mean ICP remains largely unaltered. As the brain
compliance reduces further, the P2 component of
the wave exceeds P1 and the wave becomes broader
(see Fig. 52.6B).
In 1960, Lundberg described fluctuations in ICP
waves (Fig. 52.7). 42 Lundberg A waves or plateau
waves are slow vasogenic waves seen in patients with
critical cerebral perfusion. These waves can reach

50–100 mm Hg and last between 5–20 minutes before
spontaneously subsiding. Plateau waves cause critical
cerebral ischaemia within minutes and are thought to
result from spontaneous reductions in MAP, resulting

P2

P1

P3

A
P2

P1

P3

B
Figure 52.6  Intracranial pressure waveforms in (A) the
normal state and (B) when brain compliance is reduced.

in cerebral vasodilatation. This results in increased ICP
and further reduction in CPP until maximal cerebral
vasodilatation occurs and the wave plateaus. Early
termination of Lundberg A waves can occur if MAP
is increased, thus restoring CPP. Plateau waves are
always pathological and indicative of reduced cerebral
compliance. Lundberg B waves are smaller changes in
ICP that occur every 30 seconds to a few minutes and

can be seen in normal individuals. ICP rises to levels
20–30 mm Hg above baseline before falling. Lundberg
C waves are of little clinical importance. They are of
low amplitude and occur with a frequency of 4–8/min
and are associated with variations in blood pressure.
OTHER FORMS OF NEUROLOGICAL
MONITORING
Patients with neurological illness can be monitored
using a wide range of different techniques depending
upon the condition and the institution where they are
treated. In many specialist ICUs these techniques may
be combined, often known as multimodality monitoring (MMM). Despite widespread use in specialist
centres, there is limited evidence to support their effectiveness in improving outcomes.43,44
CEREBRAL OXYGENATION
Brain tissue oxygenation can be assessed using invasive
or non-invasive methods. Intraparenchymal probes are
available that measure brain oxygen content (Pbt O2 )


Intracranial pressure in normal and pathological conditions
100

Near-infrared spectroscopy (NIRS) measures
regional cerebral oxygen saturation by measuring
near-infrared light that is reflected from brain chromophores, the most commonly used of which is oxygenated haemoglobin. The changes in the concentration of
near-infrared light are measured as it passes through
these compounds and these allow calculation of their
oxygenation status. Although NIRS has proved useful
in vascular and cardiothoracic surgery, its value in the
ICU has not been proven.

A waves

0
0

40

80
Min

671

120

B waves
30
10

MICRODIALYSIS

Resps

0

1

2

1

2

Min

3

4

5

3

4

5

C waves
BP 120
90
ICP

0

Min

Figure 52.7  Lundberg waves. A waves are plateau waves
of 50–100 mm Hg lasting 5–20 minutes that compromise
CPP. B waves are smaller changes in ICP that occur every
30 seconds to a few minutes and may be associated

with variations in partial pressure of oxygen and carbon
dioxide due to changes in breathing patterns. C waves are
of low amplitude, occur with a frequency of 4–8/min and
are associated with variations in blood pressure. BP, blood
pressure; ICP, intracranial pressure.

in the adjacent white matter. Pbt O2 is the product of
CBF and the arteriovenous tension of oxygen; brain
oxygenation depends on both the adequate supply of
oxygen and its extraction. The normal range of Pbt O2
is 20–35 mm Hg. A level below 20 mm Hg has been
suggested as the threshold for therapeutic intervention with increased morbidity and mortality associated
with levels less than 10 mm Hg.
Jugular bulb venous oxygen saturation (Sjv O2 ) provides information on the global utilisation of oxygen
by the brain. A catheter is placed into the dominant
internal jugular vein and advanced into the jugular
bulb. Normal values for Sjv O2 are between 55% and
75%. Low levels of Sjv O2 are indicative of ischaemia
resulting either from reduced oxygen delivery or
increased demand. High levels of Sjv O2 may indicate
hyperaemia, reduced demand or tissue death.

Brain metabolism can be monitored using cerebral
microdialysis probes. Dialysis fluid is passed through
the catheter which has a semipermeable membrane.
This allows molecules below the size of the membrane
to equilibrate along the concentration gradient. The
technique analyses substrates such as lactate, pyruvate, glucose, glutamate and glycerol in the extracellular fluid of subcortical white matter. Glutamate is
an excitatory neurotransmitter that is associated with
injury and inflammation. Glycerol is a lipid-rich component of neurons and is indicative of irreversible

cell death when levels are elevated. Lactate, pyruvate
and the lactate/pyruvate ratio are used as markers of
hypoxia or ischaemia.
CEREBRAL BLOOD FLOW
Invasive measurement of regional CBF can be achieved
using thermal diffusion probes or laser Doppler flowmetry. The thermal conductivity of brain tissue varies
in proportion to CBF. The most commonly used CBF
catheter introduces heat in subcortical white matter
and calculates the rate of temperature dissipation at a
set distance, allowing calculation of local CBF. Laser
Doppler flowmetry involves placement of a small
Doppler probe within the brain tissue. Doppler change
of laser light is used to measure the movement of red
cells within the cerebral microcirculation. Both techniques are limited to the assessment of a small area of
cerebral tissue.
TCD ultrasound measures blood flow velocity in
the major intracranial vessels. Although TCD measures velocity rather than flow, it can be used to assess
relative changes in CBF. TCD is most widely used to
assess vasospasm following SAH, high flow velocity being indicative of a reduction in vessel diameter.
Comparison of the velocities in the MCA and the
external carotid artery (the Lindegaard ratio) can help
distinguish between vasospasm and hyperaemia.
ELECTROENCEPHALOGRAPHY
The EEG represents the summation of the brain’s electrical activity as recorded from the scalp. It can be
used to detect seizure activity, especially when there


672

Cerebral protection

is concern regarding non-convulsive status epilepticus, to monitor the response to antiepileptic therapy
and to help to prognosticate in patients with persistent coma.45 EEG monitoring is also useful in diagnosing pseudo-status epilepticus due to psychogenic
problems, allowing rapid withdrawal of inappropriate
drug therapies.
TIMELINESS OF SPECIALIST CARE
There is a wide body of evidence supporting the care
of brain-injured patients in specialist facilities which
are often distant to the hospital of first attendance.46–50
Although many secondary preventive measures can
be successfully applied pre-hospital or in a regional
hospital prior to transfer to definitive care, rapid diagnosis and transfer is essential to optimise outcomes.
The Society of British Neurosurgeons recommends the
evacuation of acute extradural or subdural haemorrhages within 4 hours. Major trauma networks advocate direct transfer to specialist care if patients are
within a certain time of the specialist centre. Automatic
admission criteria have been developed to facilitate
rapid transfer from other hospitals without waiting for
‘permission’ to transfer.51
The primary treatment of SAH is occlusion of any
identifiable aneurysm that has ruptured. Up to 15%
of patients re-bleed within a few hours of the initial
bleed, often before definitive treatment can be undertaken. The European Stroke Organisation recommends
that the aneurysm should be treated as early as possible to reduce the risk of re-bleeding, ideally within 72
hours of onset of first symptoms.36 The volume of cases
treated and the availability of endovascular services
and neurological intensive care are also important
determinants of outcome from SAH. The American
Heart Association recommends that low-volume hospitals (<10 SAH cases per year) should consider early
transfer of patients to high-volume centres (>35 SAH
cases per year) with experienced neurovascular surgeons, endovascular specialists, and neuro-intensive

care services.37 Similarly, ICH is a medical emergency
that needs to be diagnosed and managed swiftly.
Expansion of the haematoma and clinical deterioration
are common in the first few hours. Among patients
undergoing head CT within 3 hours of ICH onset, up
to 38% have expansion of more than one third of the
initial haematoma volume on follow-up CT.38 While
awaiting transfer for specialist care, it is important to
minimise the risk of haematoma expansion by fully
reversing any prescription anticoagulants and reducing elevated blood pressure.52
In several countries, acute stroke care has also
been centralised, creating specialist centres to which
patients are taken rather than going to the nearest hospital.53,54 This has increased access to specialist care and
thrombolysis. With the advent of other time-critical

therapies such as intra-arterial thrombectomy,55 it is
likely that there will be continued centralisation of care for
acute stroke.
REHABILITATION
Early access to specialist rehabilitation that continues
into the community is essential to maximise the recovery following neurological injury. Early mobilisation
has been shown to enhance recovery and improve
functional outcomes for patients in acute and intensive care settings including neurosciences ICU.56 There
is now a substantial body of evidence to support the
effectiveness and cost-effectiveness of specialist rehabilitation.57 Despite a longer length of stay, the cost
of providing early specialist rehabilitation is offset by
longer-term savings in the cost of community care.58
KEY REFERENCES
14.Andrews PJD, Piper IR, Dearden NM, et al.
Secondary insults during intrahospital transport of

head-injured patients. Lancet. 1990;335:327–330.
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