NEUROINTENSIVE CARE
The management of
ischaemic stroke
Robin S Howard
Abstract
Ischaemic stroke often leads devastating long-term neurological
sequelae. There are five interventions that improve the outcome after
a stroke: management within a stroke unit, intravenous thrombolysis,
mechanical clot retrieval, aspirin within 48 hours, and decompressive
hemicraniectomy for malignant middle cerebral artery (MCA) stroke.
The benefits of intravenous thrombolysis up to 4.5 hours are now
well established, but the recent development of clot retrieval has radi-
cally altered the acute management of stroke. The development of late
complications remains the most important factor determining outcome
and it is essential to ensure homoeostasis is maintained during the
acute phase of care to reduce the risk of late deterioration.
Keywords Clot retrieval; ischaemic stroke; thrombolysis
Royal College of Anaesthetists CPD Matrix: 2F01
Introduction
Stroke is defined as ‘rapidly developing clinical signs of focal (or
global) disturbance of cerebral function, with symptoms lasting
24 hours or longer, or leading to death, with no apparent cause
other than of vascular origin.’
Stroke is a major public health problem, being the third most
common cause of death after myocardial infarction and cancer,
and the leading cause of adult disability. Stroke accounts for 9%
of deaths in England and Wales. The incidence of stroke has
fallen over the last 10 years and prevalence increased, as a result
of more effective primary prevention and treatment.
Ischaemic stroke is the result of vessel occlusion from in situ
thrombosis, embolism or haemodynamic failure. Embolism may
be from artery to artery (30e40%) or from the heart (30e40%).
In 25% of cases, disease of the walls of small penetrating intra-
cranial blood vessels is responsible for lacunar infarction.
Causes and risk factors
The risk factors for ischaemic stroke are summarized in Box 1.
Clinical syndromes of cerebral ischaemia
Transient ischaemic attacks: the symptoms of transient
ischaemia are usually negative, maximal at onset and last typi-
cally for a few to 30 minutes. TIAs are associated with a high rate
Robin S Howard PhD FRCP FFICM is a Consultant Neurologist and
Head of Service at St. Thomas’ Hospital, Guy’s and St. Thomas’ NHS
(Foundation) Trust; and Consultant Neurologist at the National
Hospital for Neurology and Neurosurgery, London, UK. Conflicts of
interest: none declared.
ANAESTHESIA AND INTENSIVE CARE MEDICINE 17:12
Learning objectives
After reading this article, you should be able to:
C describe the initial assessment and managemant of acute
ischaemic stroke
C identify patients eligible for intravenous thrombolysis
C describe the criteria for endovascular intervention in stroke
patients
of subsequent stroke: one-third of all untreated patients subse-
quently have a stroke. The immediate risk is high: 20% of strokes
occur within a month and 50% within a year. The differential
diagnosis of TIA is summarized in Box 2.
Lacunar stroke: lacunes are small, subcortical or brainstem in-
farcts ranging from 1 to 15 mm in size. They are caused by oc-
clusion of small penetrating vessels most commonly arising from
the MCA and basilar artery.
Large vessel occlusion: the main clinical distinction between
large vessel occlusion and lacunar infarction in the carotid cir-
culation is the presence of cortical signs (eye deviation,
dysphasia, neglect syndromes, hemianopia). The hemiparesis
produced by MCA occlusion affects the arm more than the leg.
Internal carotid artery disease e symptoms are produced
either by embolism, thrombus formed on ulcerated plaque,
haemodynamic failure from severe stenosis or carotid artery
occlusion.
Total MCA e the MCA may be affected by embolism or
thrombosis in situ. If the main trunk occludes then the whole
territory infarcts with conjugate eye deviation (frontal lobe
damage), aphasia (dominant hemisphere), hemiplegia, hemi-
sensory loss and hemianopia (parietal and temporal lobe dam-
age). Patients with complete MCA syndromes occasionally
develop fatal brain swelling (malignant MCA oedema) within 48
hours of onset, leading to death from coning. In appropriate
cases surgical decompression is required.
MCA branch e upper branch occlusion affecting frontal
structures produces hemiparesis, hemisensory loss, ocular devi-
ation and non-fluent motor dysphasia (expressive).
Anterior cerebral artery (ACA) e this territory is rarely
affected, ACA occlusion leads to contralateral hemiplegia with
the lower limb predominantly affected.
Posterior cerebral artery (PCA) e commonly embolic and
causes hemianopia and neglect syndromes. Involvement of the
thalami and posterior-medial temporal lobeslead to confusion,
dysphasia (thalamic) or memory impairment (thalamic or tem-
poral). If both PCA territories are infracted, as may happen when
an embolus lodges at the top of the basilar, cortical blindness and
confusion ensues.
Vertebral artery e occlusion of the vertebral arteries causes
infarction of the dorsolateral medulla leading to lateral medullary
syndrome. This results in a Horner’s syndrome, dissociated
(temperature and pain) sensory loss on the ipsilateral side of the
face and the opposite side of the body, nystagmus, ataxia of the
ipsilateral limbs, and ipsilateral palatal and vocal cord paralysis.
591 Crown Copyright Ó 2016 Published by Elsevier Ltd. All rights reserved.
 NEUROINTENSIVE CARE

to establish whether the patient has had an ischaemic stroke and,

Risk factors for ischaemic stroke if so, the localization and severity. A focused and detailed
neurological examination facilitates anatomical localization, and
C Age thereby provides the basis for interpreting the imaging findings
C Blood pressure and identifying underlying causes.
C Smoking
C Diabetes mellitus Emergency treatment: the initial management of acute stroke
C High total cholesterol and low-density lipoprotein (LDL) focuses on stabilization of the airway, breathing and circulation,
C Alcohol consumption followed by an assessment of the neurological deficits and
C The presence of asymptomatic carotid disease of greater than comorbidities to identify patients eligible thrombolysis and those
75% at particular risk of the complications of acute stroke.
C Illicit drugs Admission to a stroke unit and multidisciplinary rehabilitation
C Sickle cell disease are vitally important as are complementary to medical treat-
C Antiphospholipid antibodies and syndrome ments. Successful stroke unit care also pays critical attention to
C Cardiac disease the prevention of complications and the prevention of recurrent
 Atrial fibrillation stroke.
 Sick sinus syndrome through atrial dysfunction may also
result in embolism Investigation: emergency investigations including blood
 Valvular heart disease glucose, electrolytes and renal function, full blood count, cardiac
 Rheumatic markers, coagulation profile and ECG are essential.
 Endocarditis on native or prosthetic valves CT or MRI scan should be performed immediately on admis-
 Myocardial infarction sion of the patient to hospital. Early CT scan changes are seen in
 Paradoxical embolus due to patent foramen ovale 60% within 6 hours of stroke onset (Figure 1). They include:
 cortical sulcal effacement
Box 1
 loss of the insular ribbon
 blurring of the greyewhite interface
 obscuration of lentiform nucleus
 hyperdense artery sign (intravascular thrombus).
Differential diagnosis of TIA
A cerebral and/or neck CT angiogram/MR angiogram should
C Migraine with focal symptoms be undertaken to exclude arterial deception and carotid or
C Transient global amnesia vertebral occlusive disease. Brain haemodynamic measurements
C Epilepsy with CT or MRI perfusion allow the identification of viable tissue
C Tumours at risk of infarction (penumbra). Diffusion-weighted imaging is
C Subdural haematomas the most reliable technique for detecting acute ischaemic stroke
C Multiple sclerosis as early as 30 minutes from symptom onset. Conventional MRI
C Hypoglycaemia sequences are most useful for assessing the extent and age of
C Syncope subacute and chronic infarcts.

Box 2
Basilar artery e in the medulla, lower cranial nuclei may be
affected giving rise to a bulbar or pseudobulbar palsy but above
the medulla, pontine infarction can cause a gaze paresis, inter-
nuclear ophthalmoplegia, pinpoint pupils or ‘locked-in’
syndrome.
Management of acute stroke
In the first few hours after ischaemic stroke, measures are
designed to
 restore blood flow (reperfusion)
 preserve the ischaemic penumbra (neuroprotection)
 prevent early recurrence (antiplatelet treatment).
Initial assessment: assessment depends on determining the
history and excluding alternative causes. It is important to define
the onset of symptoms and the progression of neurological deficit
Maintenance of homoeostasis
Initial supportive treatment is essential to improve functional
outcome. This includes:
 Stabilization of airway, breathing and circulation.
 Oxygen saturation should be monitored routinely and
hypoxaemia treated appropriately (SatO2 >95%).
 Blood sugar levels are elevated in about one-quarter of all
stroke admissions and elevated blood glucose on admis-
sion is a risk factor for haemorrhagic transformation of the
acute infarct. The optimal level is 6e9 mmol/L and insulin
may be necessary to achieve this.
 Blood pressure e elevated blood pressure should not be
lowered acutely unless the patient is a candidate for
thrombolysis, has hypertensive encephalopathy, malig-
nant hypertension or the blood pressure readings are
persistently above an arbitrary threshold of 220/120.
 Hypotension should be corrected promptly by raising the
foot of the bed, fluid replacement and stopping hypoten-
sive medication.
 Pyrexia should be treated aggressively.

ANAESTHESIA AND INTENSIVE CARE MEDICINE 17:12 592 Crown Copyright Ó 2016 Published by Elsevier Ltd. All rights reserved.
 NEUROINTENSIVE CARE
Figure 1 CT scan of middle cerebral artery infarction showing hyperdensity in left terminal ICA and middle cerebral artery consistent with
thrombosis, also showing cortical sulcal effacement, loss of the insular ribbon, blurring of the greyewhite interface, obscuration of lentiform
nucleus and extensive established infarction involving left hemispheric white matter.
Intravenous thrombolysis: ‘Time is brain’ and early treatment is
the most important factor for successful thrombolysis. The ben-
efits have been confirmed in numerous, randomized, controlled
clinical trials using tissue plasminogen activator (r-tPA) at a
dosage of 0.9 mg/kg within 4.5 hours of stroke onset. Treatment
given within 1.5 hours approximately doubles the odds of near-
complete recovery compared to administration at 3.0e4.5
hours. Strict adherence to r-tPA administration and post treat-
ment protocols minimizes the risk of complications (Box 3). The
main side effects are intracranial haemorrhage (about 7% of
cases), gastrointestinal bleeding, allergic reactions and hypoten-
sion. Predictors of intracranial haemorrhage include time of
thrombin lysis and the size of the core infarct.
Intra-arterial thrombolysis: at present there is no clear evidence
that intra-arterial thrombolysis is superior or safer to intravenous
thrombolysis but it may have a role in the treatment of basilar or
vertebral artery occlusive strokes within 24 hours of symptom
onset because, untreated, the mortality rate can be extremely
high without recanalization.
Mechanical clot retrieval: for patients presenting with stroke
secondary to proximal intracranial artery occlusion it has been
shown in several trials that the best outcome can be achieved by
ensuring that the vessel is rapidly recanalized by mechanical clot
retrieval procedures that aim to physically remove persisting clot
in proximal intracranial vessels using retrievable stents. Patients
with proximal vessel occlusions, severe neurological deficit
(NIHSS >18), a viable penumbra on MRI and good functional
premorbid status benefit the most.
Antiplatelet therapy in acute stroke: aspirin (100e300 mg
daily), given within 48 hours of onset, has a small but significant
benefit in reducing the rate of recurrent ischaemic stroke. The
addition of clopidogrel seems to improve the benefit.
ANAESTHESIA AND INTENSIVE CARE MEDICINE 17:12
Treatment of cerebral oedema: mannitol may provide a tem-
porary respite pending surgical treatment. Paralysis and hyper-
ventilation are rarely of benefit. Instead, decompressive
neurosurgery with a large craniectomy should be considered.
Neuroprotection: a number of neuroprotective agents and stra-
tegies have been suggested. These include glutamate and calcium
antagonists, corticosteroids and free radical scavengers. At pre-
sent none has been shown to benefit in clinical practice. Similarly
hypothermia has shown an increased incidence of medical
complications without significant benefit.
Decompressive surgery: the mortality of malignant middle ce-
rebral artery infarction with cerebral oedema is up to 80%.
Decompressive hemicraniectomy undertaken within 48 hours of
symptom onset increases survival significantly, often at the cost
of severe residual disability.
Management of progressive stroke: about one-third of patients
with ischaemic stroke progress in the first day after onset. Acute
progression is even more common in patients with cerebral
haemorrhage because of continued bleeding and enlargement of
the haematoma. In ischaemic stroke, the causes of early pro-
gression include extension of the area of ischaemia from
thrombus propagation, recurrent embolism, or enlargement of
the penumbra from release of cytotoxic chemicals and the local
effects of cytotoxic oedema. In patients who deteriorate after a
period of stability, a number of other causes need to be
considered:
 metabolic disturbances (e.g. low or high blood sugar, or
hyponatraemia)
 hypotension, or severe hypertension
 cardiac arrhythmias or MI
 pyrexia and infections
 dehydration
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 NEUROINTENSIVE CARE
 hypoxia (e.g. from aspiration, infection or silent pulmo-
nary embolism)
 cerebraloedema or hydrocephalus
 haemorrhagic transformation of infarction
 new infarction (often from cardiac embolism) or
haemorrhage.
Guidelines for intravenous alteplase in acute ischaemic
stroke
Eligibility
C Age 18 years or older
C Clinical diagnosis of acute ischaemic stroke
C Assessed by experienced team
C Measurable neurological deficit
C Glasgow Coma Score >8
C Timing of symptom onset well established
C CT or MRI and blood tests results available
C CT or MRI consistent with diagnosis
C Time since onset <4.5 hours at start of infusion
Exclusion criteria
C Symptoms only minor or rapidly improving
C Haemorrhage on pre-treatment CT (or MRI)
C Suspected subarachnoid haemorrhage
C Active bleeding from any site
C Recent gastrointestinal or urinary tract haemorrhage within
21 days
C Platelet count less than 100  109/L
C Recent treatment with heparin and APTT above normal
C Recent treatment with warfarin and INR elevated
C Recent major surgery or trauma within the previous 14 days
C Recent post-myocardial infarction pericarditis
C Neurosurgery, serious head trauma or previous stroke within
3 months
C History of intracranial haemorrhage (ever)
C Known arteriovenous malformation or aneurysm
C Recent arterial puncture at non-compressible site
C Recent lumbar puncture
C Blood pressure consistently above 185/110 mmHg
C Abnormal blood glucose (<3 or >20 mmol/L)
C Suspected or known pregnancy
C Active pancreatitis
C Epileptic seizure at stroke onset
Cautions and limitations
C Severe neurological deficit (NIHSS >22)
C Visible changes on pre-treatment CT of infarction > one-third
of MCA territory
C Diabetic retinopathy
APTT, activated partial thromboplastin time; CT, computerized tomogra-
phy; INR, international normalized ratio; MCA, middle cerebral artery;
MRI, magnetic resonance imaging; NIHSS, National Institutes of Health
Stroke Scale.
Box 3
ANAESTHESIA AND INTENSIVE CARE MEDICINE 17:12
Treatment of lifestyle risk factors
C Lowering blood pressure
C Stopping smoking
C Lowering cholesterol by statin therapy and diet
C Optimizing treatment of other conditions that promote vascular
disease (e.g. diabetes)
C Prevention of cardiac embolism (e.g. valve surgery or anti-
coagulation for atrial fibrillation)
C Targeted treatment for atherosclerotic stenosis by carotid endar-
terectomy or stenting
C Inhibition of platelet aggregation with antiplatelet agents
C Weight loss
C Reduction in alcohol consumption
Box 4
Common medical complications of stroke
 Dysphagia, or an unsafe swallow e all patients with acute
stroke should therefore have their swallowing assessed as
soon as possible, using an agreed protocol. They should be
kept nil-by-mouth until their swallowing has been assessed
as safe. It is very likely that dehydration and starvation are
harmful in the acute stages of stroke and fluid replacement
should commence as soon as the patient is admitted if
swallowing is not safe. Feeding should be started at an
early stage. If nasogastric tube feeding is likely to be
required for more than 2 weeks, consideration should be
given to inserting a percutaneous endoscopic gastrostomy
(PEG) tube.
 Deep vein thrombosis is usually seen in severely hemi-
paretic limbs and pulmonary embolus is a rare but
important cause of death after stroke.
 Pressure sores should be avoided by frequent turning,
careful positioning and the use of appropriate bedding (e.g.
an air mattress) and early mobilization.
 Shoulder pain is a common complication of stroke, largely
preventable by good positioning of the shoulder and early
physiotherapy.
 Spasticity e early mobilization and appropriate physio-
therapy are important in limiting the development of se-
vere spasticity, and the development of contractures. Oral
drug treatment has a limited role in treating spasticity in
stroke. Local injections of botulinum toxin into individual
muscles may benefit patients in whom spasticity is causing
focal problems.
 Depression is common after stroke and is associated with
poor outcomes. It should be treated vigorously and expert
psychiatric advice sought if necessary.
 Post-stroke pain is characteristically associated with
infarction in the thalamus and often develops weeks or
even months after the onset of stroke. Standard analgesics
are often ineffective, but relief may be obtained with tri-
cyclic antidepressants, particularly amitriptyline taken at
594 Crown Copyright Ó 2016 Published by Elsevier Ltd. All rights reserved.
 NEUROINTENSIVE CARE
night, or anticonvulsants (e.g. gabapentin). Occasionally,
transcutaneous nerve stimulation is helpful.
 Dystonia is a rare complication of stroke involving the
basal ganglia and usually develops some months after the
initial event.
Secondary prevention
Targets for preventive measures are summarized in Box 4.
Management of carotid stenosis
Carotid stenosis: patients with recent ipsilateral TIA or non-
disabling stroke, who are fit for surgery and have significant
carotid stenosis, benefit from carotid endarterectomy to remove
the stenosis. The benefit of surgery is strongly related to the
severity of the stenosis and the recentness of symptoms.
However, patients who are asymptomatic have a low risk of
ipsilateral stroke and surgery is not indicated. A
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595 Crown Copyright Ó 2016 Published by Elsevier Ltd. All rights reserved.