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Acute Ischaemic Stroke

Table of Contents
 Preface
 Introduction
 Immediate Tasks
o Recognition of a suspected stroke and transfer
o Assessment
o Treatment
 Clinical Diagnosis
o Clinical assessment
o Mechanism and localisation of stroke
 Diagnostic Procedures
o Cerebral computed tomography (CCT) and its interpretation
o Magnetic resonance imaging
o Electrocardiogram
o Ultrasound studies
o Laboratory tests
 General Critical Care and Stroke Treatment
o Reperfusion therapy
o Which stroke patients should be admitted to the ICU?
o Managing the critically ill patient with stroke
o Secondary prophylaxis
o Rehabilitation
 Conclusion

Acute Ischaemic Stroke

Current Status 2017

Third Edition 2017
Second Edition 2010
 First Edition 2003

Learning Objectives

After studying this module on Acute Ischaemic Stroke, you should be able to:

 List the possible causes of stroke

 Describe the difference between an ischaemic and a haemorrhagic stroke
 Outline manage complications in a patient with stroke
 Describe how to initiate appropriate treatment in a timely manner

eModule Information
Expiry date: 10/2020

COBATrICe competencies covered in this module:

Competencies
 Adopts a structured and timely approach to the recognition, assessment and stabilisation of
the acutely ill patient with disordered physiology
 Manages cardiopulmonary resuscitation
 Manages the patient post-resuscitation
 Triages and prioritises patients appropriately, including timely admission to ICU
 Recognition of presenting signs and symptoms
 Identification of main acute complications and management
 Plan and prioritise investigations / monitoring - appropriate; timely
 Appropriate differential diagnosis
 Clear decision making and plan of management (including application of relevant protocols
/guidelines / care bundles)
 Effective team-working: collaboration, communication & continuity of care
 Attention to patient safety
 Obtains a history and performs an accurate clinical examination
 Undertakes timely & appropriate investigations
 Describes indications for Echocardiography (transthoracic / transoesophageal)
 Performs electrocardiography (ECG / EKG) and interprets the results
 Obtains appropriate microbiological samples and interprets results
 Obtains and interprets the results from blood gas samples
 Monitors and responds to trends in physiological variables
 Integrates clinical findings with laboratory investigations to form a differential diagnosis
 Recognises and manages the patient with neurological impairment
 Prescribes drugs and therapies safely
 Recognises and manages electrolyte, glucose and acid-base disturbances

Domain : Procedures
System: Central nervous
 Performs lumbar puncture (intradural / ‘spinal’) under supervision

System: Renal / Genitourinary system

Perioperative Care

 Manages the care of the patient following craniotomy under supervision

Comfort and recovery

 Manages the assessment, prevention and treatment of pain and delirium

 Manages sedation and neuromuscular blockade

Faculty Disclosures:
The authors of this module have not reported any disclosures.

Duration: 8 hours

Copyright©2017. European Society of Intensive Care Medicine. All rights reserved.

1. Introduction
Acute ischaemic stroke (AIS) is a common cause of morbidity and mortality throughout
the world. Over 17 million strokes occur annually worldwide, with 6 million deaths as a
result. One in 6 people will have a stroke in their lifetime, and the vast majority of
survivors have persisting neurological deficits which impair the quality of their life.

Important

Over the years there have been significant research efforts in the search for effective
treatments for stroke. Although many putative neuroprotectants with promising pre-
clinical data have failed to translate into clinical benefit, we now have five aspects of
acute stroke therapy with class I evidence of improved outcomes. They are:
1. Stroke care in specialised units (Stroke units)
2. Platelet inhibitors such as acetylsalicylic acid within 48 hours
3. Intravenous thrombolysis within 4.5 hours
4. Endovascular therapy within 6 hours
5. Decompressive craniectomy as soon as possible and ideally within 48 hours (see reference
below)

This chapter will help you better understand the complexity of treatment in AIS.

References

Learning Objectives

1. 1. Immediate Tasks

The main goals of the acute management of AIS are:

 Resuscitation and rapid recognition of the symptoms and signs of AIS

 Timely commencement of treatment appropriate to the individual, including thrombolysis or
endovascular therapy
 Early management of the key factors that can modulate outcomes, including oxygenation,
blood pressure, body temperature, and blood glucose levels
 Prompt recognition of those patients who will need intensive care unit (ICU) admission (see
“Section 5.2 Which stroke patients should be admitted to the ICU?”)

The first-line assessment and treatment are closely related and include the following
tasks:

 Securing the airway and optimising oxygenation

 Haemodynamic stabilisation, intravenous access and fluid administration
 Basic monitoring (including the rapid determination of blood glucose)
 Obtaining a clinical history
 Carrying out a physical examination
 Treatment of symptoms such as agitation, vomiting, and pain
 Recognition of contraindications to acute treatments, including thrombolysis and
endovascular therapy
 Initiation of diagnostic procedures and interventions
 Note

1. 1. 1. Recognition of a suspected stroke and transfer

The most common early signs and symptoms of acute stroke start outside the hospital.
Prompt recognition of the signs and symptoms of stroke has become an important public
health issue, and the subject of several public awareness campaigns. The FAST (Face,
Arm, Speech, Time) tool is used by UK ambulance staff for this purpose, and in the
emergency room the ROSIER (Recognition of Stroke in the Emergency Room) test can
be utilised.

Note

Current consensus is that care should take place in specialised stroke units with readily
available access to thrombolysis, antiplatelet therapy, and neurointensive and
neurosurgical care facilities. A Cochrane systematic review involving 28 trials of 5,855
patients found stroke patients who receive organised inpatient care in stroke units are
more likely to be alive, independent, and living at home one year after the stroke.
Therefore, pre-hospital care networks have been developed that facilitate patient
transfer directly to hospitals with stroke units, so that delays in starting treatment are
minimised. A systematic review suggested that stroke units reduce mortality rates
through prevention of complications. In addition, the provision of acute rehabilitation is
also likely to influence outcome. Although care on an acute stroke unit is more costly
than care on a regular ward, it reduces post-acute inpatient care costs.

References

1. 1. 2. Assessment
1. 1. 2. 1. Clinical history
Taking the clinical history is important to:

 Decide whether it is a stroke

 Determine whether the patient is within the time window for reperfusion therapy
 Obtain clues to the mechanism of the stroke (course of symptoms, risk factors). This may
aid the following technical investigative procedures
 Avoid potential complications of acute therapy

Concerning the therapeutic window, you should be aware that time is limited and that
history taking has to be focused.
 It can be very difficult to accurately establish the time of stroke onset, for example if the
patient is unable to communicate what happened to them, or if they woke up with new
deficits having gone to sleep neurologically intact. In such instances, it is important to
take the last time that they were seen without the neurological deficit(s) as the time of
stroke onset and not the time they were found or woke up. This has important
implications, particularly regarding the eligibility for reperfusion therapy.

Note

Consider the following items in history taking:

 When did the first symptoms occur? Did the patient awake with symptoms/signs?
 How have the symptoms evolved since onset? How rapidly have symptoms developed?
 Has the patient had a stroke before? Does she/he have any vascular risk factors?
 What medication is the patient taking?
 Does the patient suffer from diabetes or hypertension?
 Are there any contraindications to thrombolytic treatment, endovascular therapy or
anticoagulation?

1. 1. 2. 2. Physical examination

The neurologic examination must be focussed and done with simultaneous

quantification of the NIHSS (National Institutes of Health Stroke Scale) in the Emergency
Room (ER). Neurological screening examination in this setting can follow the NIHSS
evaluation as follows:

 Level of consciousness: orientation in time and place

 Cranial nerves: pupils, visual fields, eye movements, facial weakness
 Higher cortical dysfunction (aphasia, neglect)
 Limb power: presence of drift/reaction to pain (in patients with reduced consciousness)
 Presence of limb ataxia
 Sensory examination
 Reflexes: including biceps, triceps, knee and ankle jerk, plantars (Babinski).

Note

Note
 A general physical exam is also important, and may suggest the underlying aetiology of
the stroke and any associated complications. It should include:

 ABC assessment
 Observation for early signs of dysphagia, preferably with a validated assessment form
 Cardiovascular examination for evaluation for concomitant heart disease, atrial fibrillation,
other arrhythmias, carotid bruits, and/or murmurs
 Respiratory examination, including evaluation for the presence of pulmonary oedema or
(aspiration) pneumonia

Note

1. 1. 2. 3. Emergency diagnostic tests

The following tests are recommended as emergency diagnostic tests in patients with
AIS

All patients:

 Cranial imaging (see note below)

 Blood glucose (hypoglycaemia is a stroke mimic)
 Oxygen saturation (the most important vital sign to monitor in a patient with stroke)
 Serum electrolytes/renal function tests*
 Complete blood count, including platelet count*
 Markers of cardiac ischemia*
 Prothrombin time/INR*
 Activated partial thromboplastin time*
 ECG*

Note

Selected patients:

 Thrombin time and/or ecarin clotting time if it is suspected the patient is taking direct
thrombin inhibitors or direct factor Xa inhibitors
 Liver function tests
 Toxicology screen
 Blood alcohol level
 Pregnancy test
 Arterial blood gas analysis (if hypoxia is suspected)
 Chest radiography (if lung disease is suspected)
 Lumbar puncture (if subarachnoid haemorrhage is suspected and CT scan is negative for
blood
 Electroencephalogram (if seizures are suspected)
 Duplex sonography of the intracranial vessels
 Echocardiography

Of note, although it is desirable to know the results of the tests marked with an asterisk
(*) prior to commencing thrombolysis, the American Stroke Association guidelines
emphasise that thrombolysis should not be delayed while awaiting the results of these
tests unless:

1. There is clinical suspicion of thrombocytopaenia

2. The patient has received heparin or warfarin, or
3. The patient has received other anticoagulants (direct thrombin inhibitors or direct factor Xa
inhibitors)

Note

References

1. 1. 3. Treatment
A consensus panel convened by the National Institutes of Neurological Disorders and
Stroke (NINDS) established time targets for the evaluation of stroke patients in the
Emergency Department. They are:

 Door to physician ≤ 10 min

 Door to stroke team ≤ 15 min
 Door to CT initiation ≤ 25 min
 Door to CT interpretation ≤ 45 min
 Door to drug (≥80% compliance) ≤ 60 min
 Door to stroke unit admission ≤ 3 hours

The management principles for AIS are highlighted in the following table.

Table 1:Immediate management of acute ischaemic stroke

Intervention Recommendations
 Continuous pulse oximetry

Airway, oxygenation If intubated: regular ABG to maintain PaO2 levels >80

and ventilation mm Hg (10.6 KPa)

In self-ventilating patients: SpO2 > 92% during

endovascular procedures and >94% on ICU

Regular BP monitoring (at least every 3 min during

endovascular treatment) and prevention of extremes of
BP

Invasive BP monitoring in those with unstable BP and/or

necessitating active hemodynamic management and/or
MV

Acute BP lowering is currently only recommended

Blood pressure
before commencing thrombolysis (< 185/110 mm Hg for
24 h after thrombolysis) or in the presence of extreme
hypertension (>220/120 mmHg) in those without severe
comorbidities (e.g. severe cardiac failure, aortic
dissection, hypertensive encephalopathy) not
undergoing thrombolysis – IV labetalol, urapidil,
clevedipine or nicardipine can be used.
First-line treatment of hypotension is fluid resuscitation,
followed by norepinephrine and/or metaraminol

Regular (at least hourly) glucose monitoring

Continuous insulin infusion to prevent hyperglycaemia

Blood glucose
monitoring
 Target during endovascular therapy: 70-140 mg/dL(4-
8 mmol/l)
 Target in the ICU: 140-180 mg/dL (8-10 mmol/l)

Exclusion or treatment of underlying infection

No clear evidence to direct specific temperature targets,

Temperature
but recommendations are:
management

 Target during endovascular therapy: 35-37°C

  Target in the ICU: prevent temperatures >37.5°C

Abbreviations: ABG, arterial blood gas; BP, blood pressure; MV, mechanical
ventilation.

Cerebral perfusion and the penumbra

Adequate cerebral perfusion is crucial in preserving the penumbra, where cerebral
autoregulation is impaired, and the cerebral blood flow (CBF) is passively dependent on
mean arterial pressure (MAP); post-stenotic flow requires stable circulatory conditions.

The control of blood pressure is a major issue. If the pressure is too high, this may
exacerbate reperfusion injury to the penumbra and lead to increased oedema, cellular
hypoxia or haemorrhagic transformation. If the pressure is too low, CBF in the penumbra
can decrease to a level causing irreversible neuronal damage. Additionally, this can
cause vessels in intact brain regions to dilate, which can then lead to a potential ‘steal-
effect', further promoting ischaemia in the penumbra. Most haemorrhagic strokes occur
in hypertensive patients, whose CBF autoregulation is impaired and whose blood
pressure should therefore not be lowered too aggressively. Blood pressure lowering
should always be cautious, i.e. <15% in the first 24 hours in those not receiving
thrombolysis (more aggressive blood pressure lowering is permitted prior to
thrombolysis).

Note

Notes

References

2. Clinical Diagnosis
The history allows identification of the possible cause of stroke, especially if technical
diagnostic tests are not immediately available. It is also essential for the assessment of
the reperfusion time window.

Note

2. 1. Clinical assessment
Clinical examination is important in localising the stroke, determining the extent of the
lesion, evaluating prognosis, and assessing overall stability of the patient.

Assessments influence:
 The therapeutic options in the acute phase (e.g. no intravenous thrombolysis in extending
infarction within the 3-4.5 hour window)
 Hospital management (e.g. decision about transfer to the ICU)
o Ideally, all stroke patients should be treated on a stroke unit
o Indications for admission to the ICU are shown in Section 5.2.

Why perform such a thorough clinical assessment when a cranial

CT is available?

Clinical symptoms and signs vary with the brain territory involved (Figure 1).

Figure 1: Localisation of stroke deficits can be facilitated by a good working knowledge of neuroanatomy.
This figure lists some of the commoner features by anatomical location of the stroke. A more detailed list of
potential clinical signs or symptoms by vascular territory is provided in section Large artery thrombosis or
embolism below.

Note

These symptoms can also be caused by other pathologies, such as inflammatory

processes, tumours, some metabolic disorders and intoxications. These possibilities will,
in part, need other acute diagnostic and therapeutic investigations. A thorough history
to enquire about previous symptoms is therefore important.

Note

2. 1. 1. Differential diagnosis
Stroke is a sudden or rapidly developing neurological deficit. The differential diagnostic
considerations below can be of help.
 It is important to differentiate between stroke and stroke mimics, which comprise up to
one-third of stroke-like presentations, to ensure appropriate and safe management. This
relies on thorough history-taking, clinical examination and the use of appropriate
imaging.

The principal condition to identify in the differential diagnosis of AIS is intracerebral

haemorrhage (ICH).

Clinical findings favouring the diagnosis of ICH include:

 Onset during a hypertensive crisis

 Progression of symptoms within minutes
 Early, excessive vomiting
 Early/immediate loss of consciousness
 Acute onset of headache

References

The diagnosis cannot, however, be confirmed by history and clinical examination alone.
Neuroimaging (CT/MRI) is urgently required.

Other differential diagnoses of ischaemic stroke are shown in the below table.

Table 2: Stroke mimics

Condition Comments
Can produce hemiplegia and aphasia as well as the more common
Hypoglycaemia
symptoms of confusion and reduced level of consciousness

Tumours, cerebral abscess, and intracranial bleeding such as a subdural

Intracranial space hematoma may produce a stroke-like presentation. More acute
occupying lesions presentations in the setting of tumours may be due to intratumoural
haemorrhage, seizures or the development of obstructive hydrocephalus

Seizures and the Todd’s paresis usually follows partial motor seizures, but can result from
postictal state generalised seizures too. Can also be a complication of a stroke
 Can mimic a stroke in the presence of a hemiplegic migraine, or can itself
Migraine
precipitate a stroke

Hyperglycaemia can result in focal neurological deficits and seizures.

Encephalopathies and Hypertensive encephalopathy may present with headaches and cortical
metabolic disorders blindness. Hyponatremia and hepatic encephalopathy may also cause
stroke-like presentations

Relies on a thorough systemic examination for diagnosis and

identification of a focus of infection. Sepsis can be a risk factor for stroke
Sepsis
itself, for example mycotic emboli, and when co-existing, differentiating
the two is difficult

Drug toxicity Examples include lithium, carbamazepine and phenytoin

Often presents with acute weakness or sensory disturbance that is

Functional disorders triggered, for example by a panic attack. An inconsistent clinical
examination is key to diagnosis

References

2. 2. Mechanism and localisation of stroke

Before reading the next section you may wish to refresh your memory of the normal
anatomy of the brain and the deficits likely to follow occlusion of individual cerebral
vessels. The classification of stroke subtypes helps physicians differentiate between
small vessel disease and other aetiologies.

Note

References

The following mechanisms and types of stroke do not always lead to conditions that
require to be treated by the intensivist; however, secondary deterioration in the acute
case is always possible.

2. 2. 1. Microangiopathic or lacunar stroke

The mode of onset and clinical course of lacunar infarcts often differ from those
originating elsewhere:
 Preceding transient ischaemic attacks (TIAs) (15-20%) occur shortly (several days) before
onset of infarction, tend to occur in clusters and are more stereotypical compared with large
vessel TIAs
 Insidious onset and a gradually progressive, 'stuttering' course
 Lacunar lesions are small and may become symptomatic in regions with a high density of
axons and with multiple extensions, e.g. the cerebral peduncles and the brainstem. They
may present as:
o Pure motor stroke
o Pure sensory stroke
o Sensory-motor stroke
o Ataxic hemiparesis
o Dysarthria-clumsy-hand syndrome

2. 2. 2. Systemic embolism
A history of cardiac disease may be mentioned by the patient, relatives or referring
doctor. This may involve: mechanical or cardiac valve dysfunction, atrial fibrillation, left
atrial and/or ventricular thrombus, dilated cardiomyopathy, recent myocardial infarction
(<4 weeks), left ventricular aneurysm, sick sinus syndrome, infective myocarditis, or
atrial myxoma.

Characteristic features in the history include:

 Sudden onset, with maximal severity at onset

 Onset usually during activity, in awake state; presentation on awakening is unusual
 Recurrent TIAs in different anatomical areas

The typical clinical presentation of various arterial territories is shown in section 3.2.3
“Large artery thrombosis or embolism” below.

2. 2. 3. Large artery thrombosis or embolism

Large vessel disease may cause stroke by post-stenotic perfusion deficit, sudden
atherothrombotic occlusion, or arterio-arterial embolism. The clinical picture may not
differ significantly from that in systemic embolism. However, the clinical history may
reveal:

 Typical atherogenic risk factors

 Frequent TIAs, e.g. amaurosis fugax (internal carotid artery stenosis), in the same arterial
territory
 Onset often during sleep or atherothrombotic stroke during activity, a gradual progression or
stepwise course over minutes to hours is characteristic (attributable to gradual accumulation
of thrombus or to lowering of blood pressure, e.g. following antihypertensive therapy).
 Acute occlusion of the basilar artery comprises around 1% of all strokes but is a medical
emergency. It can result in thalamic or brainstem infarction, and typically presents with
a sudden and severe neurological impairment dependent on the position of the occlusion
within the basilar artery. Proximal occlusions can result in quadriparesis with preserved
consciousness, whereas distal occlusions can be associated with visual and oculomotor
deficits, behavioural disturbance, somnolence and/or hallucinations. Sudden death or
loss of consciousness is also possible. Rapid treatment is essential to minimise the risk
of death, and therefore patients with acute basilar occlusion require urgent transfer to a
comprehensive neurosciences centre with interventional neuroradiology facilities for
endovascular intervention.

The typical clinical presentations of different arterial territories that may be affected by
systemic embolism, large artery thrombosis or embolism are as follows:

Infarcts of the middle cerebral artery (MCA) territory

 Contralateral motor weakness and/or sensory deficit (face and arm more than leg)
 Aphasia: language disturbances (dominant hemisphere damage) – Broca, Wernicke, or
global
 Apraxia
 Dysarthria
 Conjugated ipsilateral eye deviation in large infarcts
 Homonymous visual field defects, alone or in combination with above
 Impaired spatial perception or neglect (non-dominant hemisphere damage)

Infarcts of the anterior cerebral artery territory

 Contralateral hemiparesis and/or sensory deficit (more pronounced in the lower limbs)
 Urinary incontinence
 Apraxia
 Anosmia
 Bilateral: apathy, motor inertia and muteness

Posterior (vertebral, basilar and posterior cerebral artery) circulation infarcts (usually
embolic)

 Ipsilateral cranial nerve palsy with contralateral motor and/or sensory deficit
 Bilateral motor and/or sensory deficit
 Disorder of conjugate eye movement (vertical=midbrain, horizontal=pons)
 Cerebellar dysfunction without ipsilateral long-tract deficit
 Altered consciousness
 Dysarthrophonia, dysphagia
 Horner syndrome (also in carotid artery dissection)
 Contralateral homonymous hemianopsia
 Bilateral lesions: cortical blindness (Anton's syndrome)
 Behavioural disturbance
 2. 2. 4. Dissection of cervical arteries
Apart from cardiac embolism, consider dissection of cervical arteries. The (typically
younger) patient's history may reveal risk factors such as:

 Recent trauma
 Previous infection
 Signs of connective tissue abnormalities (hyperextensible joints, Marfan syndrome, Ehlers-
Danlos syndrome, known mitral valve prolapse).

The characteristic clinical presentation is a focal neurological syndrome in combination

with unilateral headache or neck pain, pulsatile tinnitus, and an ipsilateral Horner
syndrome in the case of internal carotid artery dissection.

Note

There are many other mechanisms of stroke and stroke-like episodes. You can find
further information in the following references.

References

3. Diagnostic Procedures
Technical diagnostic tests are performed for the following purposes:

 The main 'switch point' in the direction of your acute treatment and secondary prophylaxis
is the early differentiation of ischaemic stroke from intracerebral haemorrhage or
subarachnoid haemorrhage (SAH). This is crucial for the early management of stroke.
 Based on the physical and neurological evaluation and skilled use and interpretation of
emergency diagnostic tests, different causes of ischaemic stroke can be identified. These
may indicate the need for specific therapeutic procedures and influence the choice of a
secondary prophylaxis.

After appropriate clinical suspicion of stroke and patient stabilization, the ultimate
diagnosis relies on neuroimaging that must be performed promptly, especially for those
within the therapeutic window for thrombolysis. A 30-minute delay in commencing
thrombolysis treatment has been shown to reduce favourable three-month outcomes by
10%. Use of the NIHSS can permit objective quantification of the impairment caused by
a stroke, and its use is especially important if considering revascularization therapy.
Useful cranial imaging modalities include noncontrast CT, CT with contrast, CTA, CTP,
MRI, MRA and magnetic resonance perfusion imaging. In the acute setting, a
noncontrast CT scan of the brain is the imaging modality of choice in many units as it is
readily available and allows rapid image acquisition. In addition to differentiating
between haemorrhage and infarct, the CT scan can provide prognostic information and
exclude some stroke mimics. A contrast CT can be performed at the same time and is
highly recommended to exclude other pathologies, for example intracranial tumour, as
a cause for the patient’s clinical status - a contraindication to thrombolysis. Magnetic
resonance imaging (MRI) has higher sensitivity and specificity in detecting ischemia than
CT, and is increasingly being used in the acute phase after AIS. However, it is more
time-consuming, less accessible, and not as well tolerated by patients than CT. It also
presents logistical difficulties in comatose, ventilated patients.

Additional imaging is often performed to aid diagnosis and management, although it

should not delay thrombolysis in eligible patients. CT angiography (CTA) can identify the
site of arterial occlusion, collateral circulation, and underlying pathophysiology such as
vessel dissection, and can be conducted at the same time as the structural CT image.
MR angiography can also provide this information. CT and MRI perfusion imaging can
help delineate the necrotic core and ischemic penumbra, as well as evaluation of
collateral supply.

References

3. 1. Cerebral computed tomography (CCT) and its interpretation

According to their density, the various structures of the head absorb radiation to a
different degree. The higher the density i.e. their absorption of radiation, the more
opaque is their appearance on the scan: bone, intraparenchymal calcification > blood >
thrombosed vessel > grey matter (e.g. thalamus, basal ganglia, cortex), white matter >
oedematous brain tissue.

The addition of CT angiography (CTA) and CT perfusion will not only help to make the
diagnosis of stroke, but these techniques will provide the physician with information on
location of vessel occlusion, presence and quality of collateral blood flow, cerebral blood
flow, cerebral abscesses and cerebral blood volume. These will allow the use of the so-
called ASPECTS score, which has some prognostic value regarding reperfusion and
clinical outcome.
Notes

It has been shown that patients with an ASPECTS score of ≤7 have a worse functional
outcome score at 3 months, and an increased risk of thrombolysis-related parenchymal
haemorrhage.

References

Note

The following video shows an axial CT head scan of a male patient who presented with
left sided hemiparesis. It demonstrates a right-sided ischaemic stroke in the territory of
the right MCA.

CT Right MCA Stroke

Interpretation
The patients in images 1 and 2 (Figure 2) both presented with severe right-sided
hemiparesis and aphasia. The onset of symptoms in both cases was two hours before
the scan was taken.

Figure 2: Axial CT scans of two different patients with stroke due to different aetiologies.

The patient in image 1 is a 72-year-old male who has a hyperdense left MCA (arrow).
This is a sign of thromboembolic material within the lumen of the MCA and supports the
diagnosis of an acute ischaemic stroke.

By contrast the patient in image 2 (Figure 2) is a 45-year old hypertensive smoker who
has had an intracerebral haemorrhage (star) with extension into the ventricular system
(arrows). Given the presence of intraventricular haemorrhage, the patient is at risk of
hydrocephalus.
Despite both patients presenting in a similar manner, the underlying aetiology of their
symptoms is completely different, emphasising the importance of early cranial imaging.
CT imaging is able to reliably differentiate between ischaemic and haemorrhagic stroke
– as in the two cases here – which avoids the risk of administering thrombolysis to a
patient with intracranial haemorrhage.

CT imaging can also give an indication of the age of the stroke. Look at images 3 and
4, below. Both patients woke up with a left-sided hemiparesis.

Figure 3: The two patients in images 3 and 4 awoke with left-sided hemiparesis, but their scans reveal a
difference in the age of their stroke.

Image 3 (Figure 3) may appear normal on initial review, but on closer inspection, it is
possible to see early cranial CT signs of infarction. These include loss of grey-white
matter differentiation and hypoattenuation of deep nuclei, and cortical hypodensity with
associated parenchymal swelling and gyral effacement. In image 3 (Figure 3), there is
hypoattenuation of the right lentiform nucleus (small arrows) relative to the left lentiform
nucleus, as well as some loss of the right insular ribbon (large arrow).

Image 4 (Figure 3) shows a more established infarction of the right lentiform nucleus
(arrows).

The density will further decrease during subsequent days, indicating a progressive
liquefaction of the infarcted tissue. After several weeks, resorption of a haemorrhage will
also lead to a hypodense lesion, often considerably smaller than the primary hyperdense
lesion.

If the cranial CT has just been performed and the patient is still within the therapeutic
window, do not waste time with ultrasound evaluation; consider CT angiography for
quick and safe assessment of the patency or occlusion of large intracranial vessels
(Figure 4). Ensure that this procedure does not delay treatment.
Figure 4: Coronal CTA scan with 3D reconstruction of a patient who presented with a dense right
hemiparesis and aphasia. The CTA shows complete occlusion of the left MCA (red arrow).

3. 2. Magnetic resonance imaging

Magnetic resonance imaging (MRI) has become increasingly established as an

investigative tool for the diagnosis of acute stroke in many hospitals. The equipment is
not, however, available in all hospitals admitting and treating patients with stroke.

MRI is more sensitive than CT scan in detecting hyperacute stroke. Diffusion-weighted

imaging (DWI) can show alterations minutes from the ictus time (Figure 5). Perfusion-
weighted imaging (PWI) is helpful in quantifying ischemic penumbra tissue. The
PWI/DWI mismatch show both the size of the perfusion lesion and diffusion lesion. MRI
angiography (MRA) can visualise large vessel occlusion or stenosis. MRI with fat
suppression technique, may confirm a suspected dissection and demonstrate the mural
haematoma. Stroke MRI, including MRA/DWI/PWI, can be helpful in patients who wake
up with strokes or those who present later in the time window for assessing the potential
benefits of thrombolysis. Sometimes, intravenous thrombolysis can be initiated, and
stroke MRI is then performed without time loss with the purpose of gaining more
information and further guiding reperfusion therapy (bridging concept). In the case of
haemorrhagic stroke, MRI might immediately provide information on the underlying
cause such as arteriovenous malformations.
Figure 5: Diffusion-weighted MRI demonstrating increased DWI signal, in keeping with acute ischaemic
stroke, located in the region of the left basal ganglia and insula.

References

3. 3. Electrocardiogram
An electrocardiogram (ECG) is indispensable because of the high incidence of heart
disease in stroke patients. Arrhythmias, in particular atrial fibrillation, or recent
myocardial infarction may be responsible for emboli.

3. 4. Ultrasound studies
Continuous wave (cw)-Doppler of extracranial arteries and pulsed wave (pw)- Doppler
of intracranial arteries facilitates identification of an occluded or stenotic vessel,
evaluation of the quality of collaterals, and confirmation of reperfusion. Duplex
sonography allows visualisation of the extracranial vessels with good quality
visualisation of intracranial vessels in patients with sufficient temporal bone windows.
Currently, vascular pathology including stenoses/dissections/thrombi/atherosclerosis
can be detected over a wide range of cerebral vessels. Doppler evaluation is non-
invasive and repeatable and is, therefore, excellent for dynamic assessments over time.
It is, however, quite investigator-dependent. It is very important to keep in mind that
ultrasound must not delay radiographic cerebral imaging.

What is the impact of the result of an ultrasound study during the

acute phase?
Other ultrasound studies include transthoracic and transoesophageal echocardiography
to screen for cardioembolic conditions. They are not usually performed acutely but may
be useful within the first 24 hours after the onset of stroke.

3. 5. Laboratory tests
The following tests are important in the management of stroke patients. They have been
sub-divided into urgent (U) and subsequent (S) tests.

Table 1: Tests in stroke patients management

Category Type of test Importance

For hypo- or hypernatraemia.
U Electrolytes Important for cerebral oedema,
seizures and arrhythmias

Hypoglycaemia may mimic stroke and

has to be treated immediately.
U Glucose Hyperglycaemia may increase
infarction size and impair late
functional outcome

Anaemia may aggravate brain

U Haemoglobin/Haematocrit/RBC/WBC ischaemia. Haemoconcentration may
impair oxygen supply to the penumbra

Elevated serum urea and creatinine

indicate renal insufficiency –
U Blood urea and creatinine
nephrotoxic agents and contrast agents
should be avoided where possible

Important to detect associated

U CK, CKMB, Troponin I
myocardial infarction

To eliminate chronic or acute liver

U Transaminases disease (particularly in those at high-
risk)
 To check potential contraindication for
U Coagulation– Fibrinogen, APTT, INR
anticoagulation and thrombolysis

U Arterial blood gas analysis To control pO2, pCO2 and PH

Specific coagulation tests – Protein C,

S As part of aetiologies for stroke
S, At III

S Sedimentation rate, CRP To assess inflammatory context

S Cholesterol, Triglycerides As a stroke risk factor

Note

In younger patients where there is no clear cause of stroke, the following special
laboratory tests are used:

 Protein C, S, aPC-resistance
 Cardiolipin-AB
 Homocysteine
 Vasculitis-screening
 CSF (in case of suspected SAH, meningitis or vasculitis)
 Urine toxicology screening.

Why is an initial laboratory assessment so important in the acute

setting? Which variables may influence your diagnostic and
therapeutic options?

Blood glucose: Exclusion of hypoglycaemia is crucial since hypoglycaemia can mimic

an acute ischaemic infarction. Diagnosis and treatment of hypoglycaemia may thus
prevent misdiagnosis with possibly dangerous diagnostic and therapeutic
consequences. Furthermore, hypoglycaemia worsens functional outcome and increases
infarct size in stroke patients. At the same time, significant hyperglycaemia is associated
with a worse stroke outcome, and thus should be treated.
 Blood urea and creatinine may influence your choice of diagnostic imaging procedure
such as avoidance of IV contrast agents.

Acute phase/infection parameters: these might explain fever, which is detrimental in

stroke and may suggest the need to identify a source of infection and start antibiotic
treatment.

4. General Critical Care and Stroke Treatment

The past two decades have seen a significant change in the management approach to
patients with acute ischaemic stroke. There is now class I evidence to support five
interventions for patients with acute stroke:

1. Care on a stroke unit

2. Intravenous tissue plasminogen activator (rt-PA) within 4.5 hours of stroke onset (even if
endovascular treatments are being considered)
3. Aspirin within 48 hours of stroke onset
4. Decompressive craniectomy for supratentorial malignant hemispheric cerebral infarction
within 48 hours of symptom onset, and
5. Endovascular therapy with stent retriever in selected patients with anterior circulation stroke
within 6 hours of stroke onset

The vast majority of patients with stroke are safely managed in a stroke unit setting.
However, some patients require a level of care and monitoring that cannot be provided
on a stroke unit. In part due to a more aggressive approach to management, an
increasing number of patients with stroke are being referred and subsequently admitted
to intensive care. Appropriate triage and the decision to admit a patient to the ICU can
best be achieved through the collaboration of neurologists/stroke physicians and
intensivists.

A useful schematic of the ICU management principles for acute ischaemic stroke is
shown below (Figure 6).
Figure 6: Schematic outlining the general principles of the endovascular and intensive care management of
acute ischemic stroke ...

Figure 6: Schematic outlining the general principles of the endovascular and intensive
care management of acute ischemic stroke.Abbreviations: ABG, arterial blood gas; AIS,
acute ischemic stroke; ASPECTS, Alberta Stroke Program Early Computed
Tomography Score; BG, blood glucose; BP, blood pressure; CPP, cerebral perfusion
pressure; EEG, electroencephalography; ECG, electrocardiography; FFP, fresh frozen
plasma; ICP, intracranial pressure; ICU, intensive care unit; IPCC, intermittent
pneumatic calf compression; IV, intravenous; MCA, middle cerebral artery; PCC,
prothrombin complex concentrate; PiCCO, pulse contour continuous cardiac output;
Resp, respiratory; rFVII, recombinant factor VII; rt-PA, recombinant tissue plasminogen
activator; SIADH, syndrome of inappropriate anti-diuretic hormone secretion; TCD,
transcranial Doppler; VTE, venous thromboembolism.

4. 1. Reperfusion therapy
Reperfusion therapy, including intravenous thrombolysis, intra-arterial thrombolysis,
mechanical clot-removing devices, and angioplasty/stenting are important treatment
options in the acute stroke patient.

What is the purpose of recanalisation treatment in acute ischaemic

stroke when brain tissue is known to be irreversibly damaged within
5-10 minutes of cessation of blood flow?
 Thrombolysis

There is class I evidence supporting the use of intravenous rt-PA as soon as possible
but within 4.5 hour of stroke onset, after excluding a haemorrhagic stroke by imaging.
There are several factors to consider when evaluating a patient’s eligibility for
thrombolysis, including:

 National Institutes of Health Stroke Scale score

 Blood pressure lability
 Pre-existing anticoagulant/antiplatelet use and/or presence of bleeding diathesis
 Presence of seizures
 Recent major surgery
 History of previous stroke, intracranial haemorrhage, vascular malformation or tumour

Warning

Endovascular treatment

Five recent randomised controlled trials have confirmed that, compared to standard care
(usually intravenous rt-PA), patients with proximal cerebral artery occlusions in the
anterior cerebral circulation who are given endovascular treatment combined with
standard care have improved:

 Reperfusion rates
 Early neurological recovery
 Functional outcomes

With regards to specific types of endovascular treatment and their relative efficacy,
mechanical thrombectomy has been shown to be superior to endovascular thrombolysis,
and stent retrievers superior to first-generation mechanical thrombectomy.

One of the trials recruited patients up to 12 hours following symptom onset and still noted
clinical benefit from endovascular treatment. Only one trial showed a difference in
mortality between the intervention and control arms, and the rates of symptomatic
intracranial haemorrhage were no different between the two groups in any of the trials.

To date there are no widely accepted and adopted eligibility criteria for endovascular
therapy. Furthermore, as these trials focused on anterior circulation strokes. For
posterior circulation stroke, there is no class 1 evidence to guide treatment but it is
 known that intravenous thrombolysis is rarely effective in large vessel occlusions, and
acute basilar occlusions are generally treated through endovascular means.

Warning

All patients should undergo repeat cranial imaging 24 hours after reperfusion therapy,
to evaluate for haemorrhagic transformation.

Taken together, these data suggest that eligible patients with anterior circulation stroke
should be offered the following treatment:

 Presenting within 4.5 hours of symptom onset: intravenous rt-PA plus endovascular therapy
 Presenting after 4.5 hours but within 6 hours of symptom onset: endovascular therapy alone

References

4. 1. 1. Which stroke patients should be admitted to the ICU?

There are several indications for ICU admission, including:

 A requirement for intubation and/or mechanical ventilation

o Impaired level of consciousness (GCS ≤8) and/or evidence of brainstem dysfunction
and/or any other cause of a compromised airway
o To prevent aspiration pneumonia in any of the above
o As an adjunct therapy for elevated ICP and/or in the presence of significant cerebral
oedema
o Acute respiratory failure e.g. due to neurogenic or cardiogenic pulmonary oedema
o Generalized tonic-clonic seizures or status epilepticus
o Episodes of apnoea
 Severe stroke (National Institutes of Health Stroke Scale (NIHSS) Score >17)
 Reperfusion therapy (intravenous or intraarterial), in the presence of multiorgan failure
and/or to manage the complications of therapy (e.g. haemorrhagic transformation), and in
those undergoing local intraarterial therapy
 Large middle cerebral artery infarct volume (<145cm 3), which predicts a malignant course
 Uncontrolled derangements of blood pressure that are difficult to manage in a ward setting
 Organ support, including renal replacement therapy, noninvasive ventilation, and/or cardiac
dysfunction
 Postoperative monitoring and management following decompressive craniectomy
 Management of patients with massive stroke and high mortality risk in whom organ
retrieval/harvesting is planned

Crucial to the decision-making process about whether or not to admit to intensive care
is an assessment of the likely neurological prognosis of the patient, the presence or
absence of non-neurological organ compromise, comorbidities, and patient and/or
relative wishes. It is important to exclude and correct reversible causes of neurological
impairment prior to this assessment.

References

4. 1. 2. Managing the critically ill patient with stroke

The ICU management of stroke focuses on the monitoring and optimisation of systemic
physiological homeostasis, and the monitoring and management of intracranial
complications. Once the patient has been transferred to the ICU, monitoring (e.g. ECG,
blood pressure, pulse oximetry, and where available, other methods such as transcranial
Doppler and end-tidal CO2) and global treatment (such as insertion of cannulae and
intubation, if necessary) should be initiated according to local ICU protocols.

4. 1. 2. 1. Basic measures and principles

Some routine techniques in intensive care must be applied with caution in stroke
patients, especially if elevated ICP is present or suspected:

 Keep the head in the midline and slightly elevated at approximately 20– 30°. The midline
position is of special importance since it influences venous drainage. Placement of a jugular
vein catheter may be hazardous due to the need for neck rotation, which may impede
cerebral venous drainage and increase ICP. If required, consider femoral or subclavian
catheters.
 If analgosedation is indicated, ensure adequate, deep sedation and analgesia. Otherwise,
stimuli may increase ICP by evoking motor responses such as coughing and Valsalva
manoeuvres.
 Laryngoscopy and intubation: consider the risk of further haemodynamic impairment,
especially in those with carotid artery stenosis, keep blood pressure stable and ensure
normocapnia (modified rapid sequence intubation recommended) during these procedures.
 For intubation, short acting anaesthetic agents are recommended. Consider propofol (2–4
mg/kg) or etomidate (0.15–0.3 mg/kg) in conjunction with a non-depolarising neuromuscular
blocking agent such as rocuronium (1.0 mg/kg given in a rapid sequence) if indicated. One
must be cognisant of the increased risk of vomiting and aspiration in patients with stroke.
 Note that high PEEP levels may exacerbate intracranial hypertension, although this effect
may be less significant than previously thought (see references).
 Further analgosedation regimens should be individualised and depend on the brain
lesion, expected clinical time course and non-cerebral conditions of the patient. Agents
often involved in neurocritical analgosedation are sedatives such as midazolam or
propofol, with possible adjuncts such as clonidine or dexmedetomidine, in combination
with opioids (morphine, fentanyl, remifentanil, sufentanil) for analgesia. Use of these
drugs requires appropriate systemic and cerebral monitoring. Sedation scales are
recommended and (if available) continuous EEG monitoring.

References

4. 1. 2. 2. Oxygenation and ventilation

Hypoxaemia can exacerbate cerebral ischaemia and should be strictly avoided after
stroke. It is common following stroke and can result from:

 Pulmonary infections
 Aspiration
 Acute lung injury/acute respiratory distress syndrome
 Pulmonary embolism
 Pulmonary oedema
 Altered central regulation of respiration
 Sleep apnoea
 Respiratory muscle weakness

All patients with stroke on the ICU should undergo continuous monitoring of systemic
oxygenation through pulse oximetry. Routine oxygen supplementation does not improve
outcomes and in fact appears to be detrimental irrespective of the severity of the stroke
(see references). Oxygen supplementation should only be provided to patients if SpO2
falls below 94%, and in such instances, arterial blood gas (ABG) should be performed
to confirm systemic oxygenation as SpO2 monitoring obtained through pulse oximetry
may not correlate with true SaO2.

Indications for intubation and mechanical ventilation are discussed

in Section5.1. Which patients should be admitted to the ICU? In patients with
imminent or established hypoxia and who undergo mechanical ventilation, regular ABG
monitoring should be performed, aiming for an SaO 2 of 94% or higher, as well as
normocapnea. Primary, elective tracheostomy should be considered in patients
predicted to require prolonged mechanical ventilation (>2 weeks), and in those with
severe dysphagia and/or bulbar palsies resulting from brainstem and large hemispheric
infarction, if a reasonable outcome is predicted. Optimal timing of the tracheostomy has
been controversial, although recent evidence from a small single-centre RCT suggests
tracheostomy within 3 days reduces ICU and six-month mortality with no effect on
tracheostomy-related complications (including bleeding) when compared to
tracheostomy within 7-14 days (see references).

Dysphagia is common in patients with stroke and, given the association with aspiration
pneumonia, mandates a swallow assessment soon after admission. Patients should
remain nil by mouth until their swallow has been deemed safe. It is important that
patients with stroke receive adequate nutrition, but a recent Cochrane systematic review
found no difference in death or dependency between early and late feeding in patients
with acute and subacute stroke.

References

4. 1. 2. 3. Haemodynamic and fluid management

The majority of patients with stroke are hypertensive at presentation. The hypertension
may be associated with chronic hypertension, raised intracranial pressure, a stress
response, or a neuroendocrine response. All patients with stroke on the ICU should
undergo regular blood pressure monitoring (at least every 3 minutes during
endovascular therapy with subsequent frequency of monitoring on the ICU determined
by the results of this, otherwise BP should be monitored at least every 10-15 minutes on
the ICU for the first 24 hours, again with subsequent frequency of monitoring determined
by the results of this). Those with unstable blood pressure or who are intubated and
ventilated should have continuous monitoring via an arterial line.

There is a U-shaped relationship between blood pressure and outcome following stroke,
with both hyper- and hypotension having deleterious outcomes. Despite this, there are
no clear benefits of acutely lowering blood pressure in the hypertensive stroke patient,
and severe hypotension resulting from excessive overcorrection of hypertension could
result in compromised cerebral perfusion and potentially increased infarct volumes. It is
possible that patients with severe carotid stenosis could benefit from blood pressure
augmentation, but long-term outcome data are required to fully evaluate this. European
Stroke Organisation guidelines recommend that blood pressure be lowered to <185/110
mmHg in those undergoing thrombolysis prior to commencing treatment and for 24 hours
after. In those not undergoing thrombolysis, a more relaxed threshold of <220/120
mmHg can be used unless the patient has significant comorbidities and in particular
severe cardiac failure, aortic dissection, or hypertensive encephalopathy. First line anti-
hypertensive agents include intravenous labetalol, nicardipine, urapidil, and clevedipine.
Hypotension (dependent on the patient’s normal blood pressure, but <90 mmHg is a
reasonable threshold) should be treated with intravenous fluids followed by vasoactive
agents such as norepinephrine if this is not successful.

Fluid balance should be carefully monitored and managed on an individualised basis to

maintain euvolaemia. Particular care is required in patients with an increased
vulnerability to fluid overload and those with conditions such as the syndrome of
inappropriate antidiuretic hormone secretion. Intentional haemodilution has been shown
in a meta-analysis of 18 trials not to improve outcomes. Major stroke guidelines
emphasise a preference for 0.9% saline, while dextrose-containing fluids should be
avoided unless the patient is hypoglycaemic, due to the risk of exacerbating cerebral
oedema. There are no apparent benefits in the use of 25% albumin over saline.

References

4. 1. 2. 4. Cardiovascular monitoring and myocardial complications

Cardiac abnormalities are common in patients with stroke, in particular dysrhythmias.
Elevated cardiac troponin levels and abnormal left ventricular function are also found in
patients with stroke. Sudden death after stroke is an important but under-recognised
phenomenon, thought to result from the interaction between cardiovascular and
neurological pathology. It may be related to impaired central autonomic control
particularly if the stroke involves the insular cortex.

All patients with stroke on the ICU should have continuous electrocardiography and have
echocardiography at least once during their admission. Cardiac troponin should be
measured in the presence of ECG changes and echocardiographic evidence of
ventricular function. Minimally-invasive monitors (e.g. PiCCO) may aid haemodynamic
and fluid management in patients with cardiovascular abnormalities.

References

4. 1. 2. 5. Glycaemic control
Hyperglycaemia is present in over 40% of patients with stroke at admission. It is a
marker of illness severity and associated with, among other things, larger infarct volumes
and susceptibility to infection. Hyperglycaemia following stroke is independently
associated with increased morbidity and mortality at 90 days, and an increased risk of
intracerebral haemorrhage following thrombolysis. Importantly, hyperglycaemia may
attenuate the benefits of intraarterial thrombolysis.

For these reasons, regular serum glucose monitoring (at least every hour) and careful
glycaemic control for the patient with stroke in the ICU is essential. Tight glycaemic
control does not appear to result in deleterious outcomes, but no clinical benefit of such
an approach has been demonstrated either. Continuous intravenous infusion of insulin
is preferred over subcutaneous administration in the ICU setting. Different stroke
guidelines vary in their recommendations on serum glucose levels, but a reasonable
target advised by the American Stroke Association is 140-180 mg/dl (8.0-10.0 mmol/l).

References
4. 1. 2. 6. Temperature control
Pyrexia is common after stroke, affecting up to one half of patients, and is an
independent predictor of a poor outcome. It may occur in the absence of infection, due
to a centrally-mediated inflammatory response. In all cases, an infective source should
be excluded or treated appropriately, and the fever should be treated aggressively. In
one randomised controlled trial, high-dose paracetamol (acetaminophen, 6 g daily)
within 12 hours of stroke onset did not have any overall significant benefits. Post hoc
analyses suggested improved functional outcomes in patients with admission
temperatures of 36.5 °C or higher, and the Paracetamol (acetaminophen) in Stroke 2
trial is evaluating this further.

There is no widely accepted optimal temperature target, but it is reasonable to treat

temperatures above 37.5 °C. First-line treatment is paracetamol (acetaminophen), and
second-line therapies include intravenous metamizole, rapid infusion of cold saline (4
°C), and deployment of automatic cooling systems.

There has been significant interest in the use of therapeutic hypothermia (TH) in a range
of acute brain injuries, and there is a large amount of preclinical data suggesting it has
a neuroprotective role in acute ischaemic stroke. However, at present there is insufficient
robust clinical data to support this. The authors of a Cochrane review on the subject
found no overall benefit or harm from TH in acute stroke, but called for large clinical
trials. Ongoing trials addressing the role of TH in acute stroke include ICTuS2/3 and
EuroHYP-1, which will also evaluate the role of thrombolysis in combination with TH –
are important given that there is (in vitro) evidence that hypothermia can impair the
efficacy of thrombolytic agents.

References

4. 1. 2. 7. Anticoagulation, antiplatelet therapy, and thromboprophylaxis

Anticoagulation
In patients with stroke presumed to be of cardioembolic origin, meta-analyses have
found no significant benefit in the early use of unfractionated or low-molecular-weight
heparin as a treatment for the stroke, including when compared to aspirin. The use of
anticoagulation in the first 24 hours following intravenous rt-PA is currently
contraindicated, due to the clinical trial protocol of the landmark National Institute of
Neurological Disorders and Stroke (NINDS) trials. However, this approach requires re-
evaluation, given that there is a risk of re-occlusion following thrombolysis, and that
coronary occlusions are often treated safely with concomitant anticoagulant and
antiplatelet therapy. There is little evidence supporting the newer oral anticoagulants
such as dabigatran and rivaroxaban in this setting.

Anticoagulation for the treatment of systemic thrombosis should be discontinued in the

presence of large acute stroke (e.g. >1/3 of the MCA territory) due to the risk of
intracranial haemorrhage, and restarted only in liaison with the relevant specialists
including haematology.

Antiplatelet therapy
There is class I evidence supporting the use of high-dose (160-325 mg) aspirin within
48 hours of stroke onset, although it should not replace reperfusion therapies and should
not be used within 24 hours of thrombolysis. Evidence supporting clopidogrel or other
anti-platelets in the acute phase is less compelling. Importantly, a recent meta-analysis
found that that anti-platelet use prior to admission increased the risk of symptomatic
intracranial haemorrhage in stroke patients receiving thrombolysis; it did not worsen
outcomes.

Thromboprophylaxis
Patients with stroke are at increased risk of systemic thromboembolic events, including
deep vein thrombosis and pulmonary embolism. Prevention is supported by early
hydration, mobilisation, anti-thrombotics, and external calf compression devices. Class
I evidence supports the use of heparin for thromboprophylaxis, and low-molecular-
weight heparin has been shown to be more effective than unfractionated heparin. The
administration of heparin should be delayed until 24 hours after thrombolysis to minimise
the risk of intracranial haemorrhage. Although graduated compression stockings have
been shown ineffective at reducing thromboembolic events in stroke in two RCTs, a
large RCT of mechanical intermittent pneumatic compression found that it reduces the
risk of deep vein thrombosis and lowers the 30-day mortality, albeit non-significantly
(p=0.057).

Patients with acute stroke that are immobile on the ICU should therefore receive
prophylactic dose subcutaneous low-molecular-weight heparin (at least 24 hours after
thrombolysis), and mechanical intermittent calf compression as a standard of care. In
those with high risk for pulmonary embolism where full anticoagulation is
contraindicated, the placement of a temporary vena cava filter should be considered.

References

4. 1. 2. 8. Anaemia
Using the World Health Organisation definition of anaemia (haemoglobin <12 g/dl in
women and <13 g/dl in men), one study found over 97% of patients with severe stroke
on the ICU met these criteria. Although studies of general critical care populations
support a transfusion threshold of ~7 g/dl in the absence of serious cardiac disease,
there is a lack of appropriate evidence specifically relating to stroke. Although anaemia
should be avoided, aggressive transfusion practices cannot be recommended due to the
significant risk of adverse effects it is associated with.

References
4. 1. 2. 9. Haemorrhagic transformation
Studies suggest that symptomatic haemorrhagic transformation occurs in 5-6% of
patients with stroke who receive thrombolysis or anticoagulation. Of course,
haemorrhagic transformation can also occur without the use of thrombolysis or
anticoagulation.

Haemorrhagic transformation can be categorised as haemorrhagic infarction or

parenchymal haematoma. The former refers to petechial or confluent petechial
haemorrhage within the infarcted region and normally has few clinical consequences. In
the latter, the region is filled with a mass of blood which may encroach on surrounding
structures, resulting in midline shift and clinical deterioration.

Management of haemorrhagic transformation involves stopping any thrombolytic agents

immediately, and the administration of a combination cryoprecipitate, fresh frozen
plasma, and recombinant factor VII, although robust evidence supporting a specific
strategy or choice of agent(s) is lacking. There should be close liaison with local
haematology and blood transfusion services in all cases. Repeat cranial imaging should
be obtained in all cases of suspected haemorrhagic transformation, and cases should
be discussed with neurosurgical services. Although surgery is not required in the
majority of cases, it may be lifesaving in the presence of a large haematoma with mass
effect and midline shift.

References

4. 1. 2. 10. Neuromonitoring
The mainstay of neuromonitoring in stroke is through regular clinical examination
supplemented by radiological imaging. The vast majority of stroke patients are not
sedated, rendering most invasive neuromonitoring tools futile. The risk profile of invasive
neuromonitoring in those receiving thrombolysis is also poorly understood at present.

Intracranial pressure and cerebral perfusion pressure

Even in patients who are not clinically assessable due to sedation or impaired
consciousness, the utility of neuromonitoring tools used commonly in other acute brain
injuries is unclear. For example, even in patients with large ischaemic tissue volumes,
intracranial pressure values are often normal (<20 mmHg). There is also no significant
evidence that cerebral perfusion pressure targets have a role in the routine management
of patients with acute ischaemic stroke.

Transcranial Doppler
Transcranial Doppler ultrasonography is a non-invasive tool that is perhaps the most
promising neuromonitoring tool for stroke. There is evidence that it can:
 detect acute occlusions and stenosis (by increased blood flow velocity) of the major
intracranial vessels (anterior, middle, and posterior cerebral arteries, vertebral arteries and
basilar artery)
 help evaluate the response to thrombolysis through assessment of arterial occlusion
 serve as a prognosticating tool through evaluation of the extent of arterial occlusion and its
development over time
 assess cerebral vasoreactivity e.g. through the Diamox test(*)
 provide high temporal resolution as a bedside monitor of cerebral autoregulation (in
combination with continuous blood pressure readings)
 detect microembolism

(*) The Diamox test is a useful clinical tool for evaluating cerebrovascular reactivity.
Diamox (acetazolamide) is a carbonic anhydrase inhibitor that slowly penetrates the
blood-brain barrier and acts as a cerebral vasodilating agent. To perform the Diamox
test, a standard dose of 1000 mg of intravenous acetazolamide is administered, with
peak CBF augmentation achieved approximately 10-15 minutes later. In normal
subjects, a 30-60% increase in CBF is observed, with an abnormal response variously
defined as <10% increase in absolute CBF or absolute change of <10ml/100g/min.

The main limitations of transcranial Doppler relate to the fact that it is highly user-
dependent, and there is a procedural failure rate of 5-10% due to the absence of an
acoustic window.

References

4. 1. 2. 11. Cerebral oedema and haemorrhage

The two main intracranial complications associated with stroke are the development of
intracerebral haemorrhage and cerebral oedema, and they have an important role in the
clinical course of the patient and, ultimately, final clinical outcome. Crucially, both of
these complications can be a result of reperfusion injury and result in intracranial
hypertension, although as indicated previously, monitored intracranial pressure values
can be normal despite the presence of significant infarct volumes.

Cerebral oedema usually develops during the first 24-48 hours after the onset of stroke
(see Figure 7 below). Patients with large hemispheric and cerebellar infarctions should
be managed in a centre with prompt access to neurosurgical services, due to the higher
risk of clinical deterioration as a result of increased intracranial pressure.
Figure 7. Axial (A-C) and coronal (D-F) computed tomography imaging of a patient with MCA infarction at
initial presentation (A,D), following the development of malignant MCA infarction (B,E), and following
decompressive craniectomy (C,F).

In which patients would you expect that cerebral oedema would

become clinically significant?
Warning

Medical management of intracranial hypertension

In the presence of elevated intracranial pressure readings, or clinical signs suggestive
of intracranial hypertension, a range of measures can be instituted (see below table).
However, the medical management of intracranial hypertension is only effective for a
few hours, and the only truly effective treatment with class I evidence for large
hemispheric infarction is decompressive craniectomy (see the next section, below).

There is no role for steroids in the management of cerebral oedema associated with
acute ischaemic stroke.

Table 3: Medical management of intracranial hypertension in stroke

Treatment
Comment
modality
Should only be used as a temporising measure, as it can
Hyperventilation increase cerebral ischaemia due to cerebral
vasoconstriction

Evidence demonstrating improved outcomes in stroke is

Mannitol and lacking Hypertonic saline appears to be more effective
hypertonic saline than mannitol in reducing intracranial pressure Should
only be used as a temporising measure only, and should
 not delay surgery Should not be used as prophylaxis
before the detection of cerebral oedema

Can promptly and significantly reduce ICP in acute crises

Thiopental Requires intracranial pressure, electroencephalography,
and invasive haemodynamic monitoring

Has been used in patients with cerebral oedema

Therapeutic
unresponsive to other medical therapies A trial of surgery
hypothermia
combined with therapeutic hypothermia is ongoing

Consider possible negative longer-term side effects of repeated treatment with osmotic
agents:

 Aggravation of cerebral oedema related to migration through a permeable blood-brain

barrier, reversing the osmotic gradient and exacerbating swelling
 Dehydration and shrinkage of normal brain tissue, facilitating displacement of brain tissue
thereby increasing the risk of herniation
 Electrolyte imbalances
 Raised serum osmolarity
 Hypervolaemia with cardiac failure
 Renal dysfunction

Surgery for malignant middle cerebral artery infarction

The importance of early detection and management of cerebral oedema and
haemorrhage cannot be overemphasised, not least because of a strong (class I)
evidence base supporting surgery in patients with malignant middle cerebral artery
infarction:

 If performed within 48 hours of symptom onset in those between 18-60 years old, mortality
is reduced from 78% to 29% and a significant improvement in functional outcomes is
observed
 Equal benefit is seen in those with dominant and non-dominant hemisphere infarctions
 There is no clear influence of prior intravenous thrombolysis administration on outcomes
following surgery, although antiplatelet administration appears to increase bleeding
complications
 The effects of intra-arterial therapy on outcomes following surgery are unknown at present
 Although the evidence base supports surgery within 48 hours of symptom onset, in some
centres this is not applied so rigidly in that patients may be offered surgery on day 3, for
example. Liaison with your local neurosurgical team is critical
 In patients between 61 and 82 years old, a similar survival benefit from surgery is shown
(mortality is reduced from 70% to 33%), but surgery is associated with an increased
proportion of severely disabled survivors
 Surgery for cerebellar infarction
Patients with cerebellar stroke are at risk of rapid neurological deterioration,
necessitating particularly close neurological monitoring in this group. The evidence
guiding surgical decision-making is not as strong as for malignant middle cerebral artery
infarction, but recovery and outcomes can be good if surgery is performed promptly. It
is vital to appreciate that management with a ventricular catheter (ventriculostomy) alone
is insufficient in the presence of obstructive hydrocephalus at the level of the fourth
ventricle – suboccipital craniectomy is required to prevent neurological deterioration
from upward displacement of the cerebellum.

Consensus guidelines from the American Stroke Association recommend the following:

 Suboccipital craniectomy with dural expansion, with or without resection of necrotic tissue,
in those who deteriorate due to a cerebellar infarction
 In the presence of hydrocephalus, placement of a ventricular catheter, followed by
suboccipital craniectomy

References

4. 1. 2. 12. Seizures
Convulsive seizures
Compared to other forms of acute brain injury, convulsive seizures are not common after
acute ischaemic stroke. When seizures do occur following stroke, they are often a result
of diffuse cortical infarction. Generalised convulsive and multiple focal convulsive
seizures should be treated aggressively – phenytoin is the first line agent due to the
relative paucity of data for other agents, but levetiracetam is now the drug of choice in
some centres. Trials addressing the role of prophylactic anticonvulsants were terminated
early due to low recruitment. There is evidence of worsened long-term outcomes with
the use of anticonvulsants, but most studies addressing this used phenytoin and it
remains to be seen whether the same holds true for other agents such as levetiracetam.
At present, it is recommended that routine prophylactic anticonvulsants are not used in
patients with acute stroke.

Consensus guidelines from the neurointensive care section of ESICM recommend the
use of electroencephalography in all acute ischaemic stroke patients with unexplained
and/or persistently altered consciousness.

Non-convulsive seizures
Like convulsive seizures, non-convulsive seizures are less common following stroke
relative to other forms of acute brain injury.

Give reasons as to why pharmacological prevention of recurrent

seizures is strongly recommended.
References

4. 1. 3. Secondary prophylaxis
Not all aspects described in the following are relevant to critical care of patient with
ischaemic stroke. However, the intensivist must think ahead and take measures to
facilitate safe and optimum discharge from critical care. Even if all secondary prophylaxis
is not appropriate in the very acute phase of severe ischaemic stroke, it should generally
be initiated as soon as possible

An important component of acute stroke treatment is the prevention of further ischaemic

events. This is the purpose of secondary prophylaxis. Finding the optimal secondary
prophylaxis is as important in severe stroke as it is in transient ischaemic attacks with
minor signs. Acetylsalicylic acid (ASA, aspirin) in a dose of 160-325 mg/day may be
given before you decide on further definitive secondary prevention.

In deciding on the appropriate approach to secondary prevention for an individual

patient, the cause of the stroke, as indicated by the clinical and supplementary
examinations, is relevant (see Tasks 2 and 3).

Optimal management relies on the consideration of vascular risk factors, antithrombotic

therapy, and surgery and angioplasty where indicated. The approach to secondary
prophylaxis taken depends to an extent on the underlying aetiology of the stroke. For
further reading, please see the secondary prevention section of the European Stroke
Organisation Guidelines and the American Heart Association/American Stroke
Association Guideline.

References

4. 1. 4. Rehabilitation
Rehabilitation of the patient with stroke should be started as soon as possible. A
multidisciplinary team approach is required. You can read about rehabilitation of stroke
patients in the following references

References
 In the ICU you will have patients with reduced level of
consciousness. Should you order early rehabilitation for these
patients; if so, why and what form should it take?

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Rehabilitation in these patients is passive, using frequent passive limb and joint
movements, chest vibration and positioning strategies. These interventions can be
performed not only by the physiotherapist but also by the nurses and family members.

4. 2. Conclusion

Stroke is a sudden or rapidly developing neurological deficit due to cerebrovascular

pathology where timing is of vital importance. Crucial for the successful management of
stroke is the early differentiation of ischaemic stroke from intracerebral haemorrhage to
determine appropriateness of reperfusion therapy. There are a number of indications for
ICU admission following stroke. Increasing numbers of patients with stroke are being
admitted to ICU for the monitoring and optimisation of systemic physiological
homeostasis, and the monitoring and management of intracranial complications.
General treatment includes ensuring adequate oxygenation and ventilation, and control
of blood pressure, temperature and blood glucose.

A very important component of acute stroke treatment is the prevention of further

ischaemic events. The present approach to secondary prophylaxis depends on the
cause of the stroke as indicated by the clinical and technical examinations. Mobilisation
and rehabilitation of the patient with stroke should start as early as possible.