Management of stroke

1. Prevention and Treatment of
stroke
Prof. Mustapha A. Danesi
College of Medicine
University of Lagos

2. Definition of Stroke
 Stroke is non convulsive focal neurological
deficit from vascular events
 Major types include: Haemorrhagic stroke
which includes Subarachnoid haemorrhage and
Intracerebral hemorrhage
 Ischaemic stroke which includes athero-
thrombotic or cardio-embolic stroke, lacuna
infarction and hypoperfusion infarction.
 3-5% of hospital deaths and 3-8% of all
admissions in Africa are as a result of stroke
 The prevalence of stroke in Nigeria is 1 per
1000 and age adjusted incidence rate is
54/100,000.

3. Classification of Stroke
 Type of Stoke % Of
Total
 Ischeamic Stroke 70-80
 Atherosclerotic infarction 14-40
 Cardioembolic Infarct 15-30
 Haemorrhagic 20-30
 Intracerebral 10-20
 Subarachnoid 5-15

4. Risk factors: Hypertension
 Systolic and diastolic hypertension are risk
factors
 Over 60% of our stroke studied in Lagos
 Risk rises with increasing blood pressure
 Controlling B.P. reduces risk e.g. there is
35-40% reduction for 5-6 mmHg B.P.
reduction
 Normalizing the B.P. eliminates the risk

5. Risk factors: major cardiac disease
 Atria fibrillation: valvular and non valvular
 Mitral stenosis
 Myocardial infarction
 Atria myxoma
 Infective endocarditis
 Dilated cardiomyopathy
 Congestive heart failure

6. Risk factors: minor cardiac disease
 Mitral valve prolapse
 Mitral annular ring calcification
 Patent foramen ovale
 Left ventricular hypertrophy on ECG
 Aortic septal aneurysm

7. Sources of Cardio-embolic stroke
 Atrial fibrillation: an important independent
risk factor for stroke but only 65% of stroke in
patients with atrial fibrillation are cardio-
embolic.
 Presence of mitral stenosis, left atrial thrombus
increase the risk.
 The use of Warfarin can dramatically reduce the
risk by 68% while aspirin reduces it by only
20%.
 Atrial fibrillation is found in up to 20% of all
persons with ischemic stroke and in
approximately 50% of all cardio-embolic
strokes.

8. Congestive cardiac failre
 Congestive cardiac failure: increases the risk
of stroke by a factor of 5 and ranks second
behind atrial fibrillation as a cardiac risk factor.
The risk of stroke appears to increase with a
diminishing left ventricular ejection fraction. A
dilated left ventricle appears to have a
thrombogenic potential similar to dilated left
atrium
 Myocardial infarction: Myocardial infarction
frequently is the source of emboli to the brain.
The period of highest risk of cerebral embolism
is within the first 4 weeks of acute myocardial
infarction.
 Embolism most frequently complicates trans-
mural anterior wall infarcts; a secondary left
ventricular thrombus is the usual substrate
responsible for cerebral embolism.

9. Dilated cardiomyopathy
 Another cardiac condition that predisposes to
cerebral embolism is dilated cardiomyopathy.
 The dilated cardiomyopathies are characterized
by global ventricular dysfunction and are highly
associated with arrhythmias.
 It is this combination that leads to chronic
intra-cavitary stasis and is responsible for the
conditions conducive to cerebral embolism.
 Stasis of blood in the poorly contractile left
ventricle may predispose to left ventricular
thrombus formation and cardio-embolic stroke.
Anticoagulation with Warfarin may diminish the
risk.

10. Infective endocarditis
 Cerebral embolism is a common complication of
infectious Endocarditis . By the time of
presentation, 15-30% of patients have suffered
a stroke. If the infection is brought under
control rapidly, the recurrence stroke rate
decreases.
 Infectious emboli from valvular vegetations,
usually mitral, occur in 30% to 40% of
Endocarditis cases.
 The manifestations of septic cerebral emboli
vary from subtle protean symptomatology,
such as encephalopathy and headache, to
catastrophic intracranial haemorrhage and
death.

11. Infective endocarditis
 Up to 20% of patients develop cerebral
abscess, micro-abcesses or focal cerebritis.
 In a 15-year review of 707 endocarditis cases
from an academic medical center, stroke
occurred in 68 patients (9.6%).
 Stroke was more common with mitral (17%)
compared to aortic valve (9%) endocarditis.
 The 1-year death rate for patients with stroke
and endocarditis was 52%. Cerebral
embolization is rare in right-sided infectious
endocarditis but can occur via paradoxical
embolization through a patent foramen ovale.

12. Prosthetic cardiac valves
 Cerebral embolism is a major cause of morbidity
and mortality associated with prosthetic cardiac
valves. Rates of embolism vary depending on the
position of the valve and whether the valve is
mechanical or bioprosthetic.
 The rate of embolism in patients with mechanical
mitral valves who are not treated with
anticoagulants averages 3% to 4% per patient
year.
 Oral anticoagulants cut the risk of embolism by
one half.
 The embolism rate in patients with bioprosthetic
valves is similar to the rate in patients with
mechanical valves who are on anticoagulation.

13. Other clinical risk factor
 Diabetes mellitus
 Hypercoagulable state: Antiphospholipid,
Antibodies, Protein c free protein s
 Hyperviscosity syndrome: Polycythemia,
haemoconcentration
 Sickle cell disease
 Obesity
 Homocystenaemia

14. Social risk factors
 Cigarette smoking
 Heavy alcohol use
 Oral contraceptive
 Exercise (protect against stroke
 Low income, low education
 Drug abuse e.g. cocaine, amphetamine
 Poor nutrition (low vitamin B6 and folic
acid

15. Infection as a risk
 Chronic infections e.g dental
infections,
chronic bronchitis, helicobacter pylori
are risk factors
 Acute infection with bacteria can
precipitate ischaemic stroke
 Mechanism: Activation of
coagulation
 Infection is very relevant to third
world

16. Transient Ischemic attacks
 Transient ischemic attack is a sudden, focal
neurologic deficit lasting fewer than 24 hours,
confined to an area of the brain or eye
perfused by a specific artery, and presumed
to be of vascular origin. The 24-hour
definition distinguishing transient ischemic
attacks from ischemic strokes was arbitrarily
chosen.
 Because most transient ischemic attacks last
less than 1 hour, a proposed new tissue-
based definition of transient ischemic attack
is “a brief episode of neurologic dysfunction
caused by focal brain or retinal ischemia, with
clinical symptoms typically lasting less than 1
hour, and without evidence of acute
infarction”

17. Transient ischemic attacks
 This new definition of transient ischemic attack
has not been widely accepted.
 Most TIAs last only 5-20 minutes and occur
before 25-50% of athero-thrombotic, 11-30% of
cardio-embolic and 11-14% of lacunar infarction.
 Signs of Carotid TIA include: transient monocular
blindness, contralateral body weakness,
contralateral sensory loss, aphasia, dysarthria,
and homonymous hemianopia
 Vertebrobasilar TIA: bilateral weakness, bilateral
or crossed sensory loss or paraesthesia, bilateral
homonymous field defects; two or more of the
following – i) vertigo, ii) diplopia, iii) dysphagia,
iv) dysarthria and ataxia

18. Aetiology of Ischemic Stroke
 The etiology of stroke depends on the age of
the patient with atherosclerosis playing a more
prominent role in those older than 55 years of
age.
 Younger patients are more likely to have
Cardioembolic stroke, right-to-left shunting, or
coagulopathies associated with their stroke.
 In a population-based series, the etiology of
stroke is cardioembolic in about 30%, small
vessel disease (also known as lacunar) in 20%,
large vessel atherosclerosis in 15%, and
undetermined in 35%.

19. Warning leak of Berry aneurysm
 Sudden unusually severe headache
 Conscious with unilateral pupil
dilation
 Confirmation with CT scan, carotid
angiogram
 Clipping of the aneurysm should be
done urgently to prevent fatal
subarachoid haemorrhage

20. Recurrent Stroke
 30% of recurrence of stroke occur early
 30 day stroke recurrence: Lacunar Infarct
is 2.2%, Atherosclerotic Infarct 7.9%,
cumulative 2-year recurrence is 14%
 Predictors of recurrence are cardiac valve
disease and congestive heart failure
 Low diastolic pressure protect against

21. Recommendation for stroke
prevention
 Treat hypertension, identify risk group
 Increase physical activities
 Stop smoking, heavy alcohol, drug abuse
 Treat atria fibrillation with anticoagulants
 Treat Polycythyemia, Hypercoagulable
state with anticoagulants and
antiplatelets
 Prevent infections

22. Clinical manifestations of Stroke
 The onset of a stroke is typically sudden, although
the onset may not be recognized in some
individuals. Twenty-five percent of patients wake
up with stroke symptoms.
 Ischemic stroke is frequently dichotomized into
cortical and sub-cortical presentations and
anterior and posterior circulation distributions.
 Both cortical and sub-cortical strokes may
manifest with focal weakness, sensory loss, and
dysarthria. Therefore, these findings do not help
distinguish location.
 Aphasia (most often a left hemisphere event) and
neglect (most often a right hemisphere event)
occur most frequently with cortical strokes.

23. Clinical manifestations of Stroke
 Gaze deviation away from the side of
weakness, suggests a cortical stroke ipsilateral
to the side of gaze deviation.
 Gaze deviation toward the side of weakness
suggests a sub-cortical event, typically in the
Pons contralateral to the side of gaze deviation.
 Distinguishing anterior (or carotid territory)
from posterior (or vertebrobasilar territory)
circulation strokes is important when deciding
on the necessity and relevance of diagnostic
testing (eg, carotid imaging).
 Approximately 80% of ischemic strokes involve
the anterior circulation,and 20% involve the
posterior circulation.

24. Ischemic stroke syndromes
 Left middle cerebral artery: right hemi-
paresis/ hemi-sensory disturbance, aphasia, right
homonymous hemianopia, left lateral gaze
preference
 Right middle cerebra artery: left hemi-paresis/
hemi-sensory disturbance, left hemi-spatial
neglect, left homonymous hemianopia, right head
and gaze preference.
 Left posterior cerebral artery: right visual field
defect, impaired reading with intact writing
(alexia without agraphia), impaired colour
naming, right hemi-sensory disturbance
 Right posterior cerebral artery: left visual field
defect, visual neglect, left hem-isensory
disturbance

25. Ischemic stroke syndromes
 Anterior cerebral artery: cause contralateral
weakness more severe in the lower limb
 Vertebro-basilar : dizziness, vertigo, nausea,
diplopia, quadriparesis, crossed motor or sensory
findings (ipsilateral face, contralateral body),
truncal or limb ataxia, visual dimming, impaired
consciousness
 Internal capsule/corona Radiata: contralateral
hemi-paresis alone (pure motor stroke a
 Ventral Pons: pure motor stroke, ataxic hemi-
paresis (hemi-paresis + ataxia out of proportion
to the weakness).
 Thalamus: contralateral sensory loss alone (pure
sensory stroke.

26.  Normal adult brain cerebral blood flow is 50
mL/100g/minute to 60 mL/100g/minute.
 When cerebral blood flow falls below 18
mL/100g/minute in baboons, sensory evoked
potentials disappear.
 In the same experiment, when cerebral blood
flow fell below 12 mL/100g/minute, infarction
occurred.
 Therefore, cerebral blood flow between 10
mL/100g/minute and 20 mL/100g/minute is
considered consistent with ischemic penumbra.
 Cerebral blood flow below 10 mL/100g/minute is
considered compatible with infarction. These
delineations are not absolute because time is also
a factor in the fate of tissue.
 Hyperglycaemia has been shown to decrease the
survival of penumbral tissue, increase infarct size,
and worsen clinical outcome.
Pathogenesis and
Pathophysiology

27. Differential Diagnosis (Stroke Mimics)
 Cerebral tumour
 Subdural haematoma
 Brain abscess
 Todd’s paralysis
 Hypoglycaema
 Focal migraine
 Encephalitis
 Consider alternative diagnosis in : patients less
than 45 years, presence of seizures, presence of
papilloedema, absence of risk factors, fluctuating
level of consciousness and pyrexia at
presentation.

28. Differential diagnosis: Stroke Mimics
 Misdiagnosis of cerebral infarction occurs in
approximately 10% of cases.
 Intra-cerebral hemorrhage may mimic
ischemic stroke because the symptoms and
signs are often not distinguishable. CT scan
may be needed. However a severe headache,
neck pain, nuchal rigidity, coma, and vomiting
are more likely with a hemorrhage.
 A brain tumor, which can usually be
differentiated by a more gradual onset of
symptoms with an accumulation of deficits.
 Post ictal Todd’s paralysis following a seizures
can usually be differentiated by the prior
occurrence of simple partiak seizure. It usually
recovers within 48 hours.

29. Differential diagnosis: Stroke Mimics
 Migraines can easily be identified especially
if it is preceded by visual aura. However,
focal neurological symptoms in association
with a headache, as seen in complicated
migraines, may warrant neuroimaging.
 Hypoglycemia may also mimic stroke.
Aphasia or hemiplegia may be present with
variable drowsiness or obtundation. Blood
glucose is usually <45 mg/dl. Symptoms
resolve within hours of giving iv glucose.

30. Differential diagnosis: Stroke Mimics
 Subdural haematoma may follow trivial
head injury in elderly. Signs of chronic
raised intracranial pressure such as
bilateral 6th nerve palsy may occur. CT is
diagnostic
 Other conditions in the differential
diagnosis include cerebral venous occlusive
disease, cerebral abscess, and conversion
disorder.

31. Stroke chameleons
 These are common atypical stroke
presentations and patients may not be
recognized as having stroke
 Patients with occlusion of the posterior
branch of middle cerebral artery may
present with Wernicke aphasia. This consist
of fluent aphasia with paraphasic errors.
Patients usually talk jargons and do not
respond correctly to instructions or
questions. Because they have no paralysis,
they are misdiagnosed as psychosis or
psychiatric disease.

32. Stroke chameleons
 Infarction of mesial temporal lobe following
occlusion of posterior cerebral artery may
cause acute confusional state with
disorientation and short term memory loss
because of dysfunctions of the limbic
system.
 Chest pain mimicking myocardial infarction
may occur in patients with infarction of the
thalamus, or lateral medulla.
 Abrupt onset and presence of vascular risk
factors should alert one to possibility of
stroke

33. Cardio-embolic stroke
 Accounts for 20-57 per cent of all ischaemic
stroke
 Imaging findings of cortical infarcts in multiple
vascular territories support cardio-embolic stroke
 Haemorrhagic transformation is very common in
cardio-embolic stroke
 Patients with large embolic infarction therefore
may be particularly vulnerable to symptomatic
haemorrhagic transformation in the first few days
of systemic anticoagulation. As a result, many
clinicians do not anticoagulate patients with large
embolic infartion.

34. Clinical manifestations
 Embolic material usually originates from the heart
or great vessels such as the aortic arch or carotid
bifurcation.
 There is considerable overlap in the clinical
presentation of cerebral ischemia resulting from
embolic disease, large-vessel athero-thrombotic
disease, and small-vessel disease.
 The Cerebral Embolism Task Force set forth the
following criteria for the diagnosis of cardiogenic
cerebral embolism:
(1) neurologic symptoms of abrupt onset with
maximal severity at onset,
(2) evidence of a potential cardiac source,
(3) branch occlusions on cerebral angiography,
(4) evidence of emboli to limbs or other organs,
and (5) multiple infarctions involving more
than 1 territory.

35. Clinical manifestations
 Branch occlusions within the anterior
intracranial circulation are highly suggestive of
cerebral embolism.
 These occlusions typically manifest as restricted
deficits such as fluent aphasia or monoplegia.
Embolic syndromes of the posterior circulation
occur less frequently.
 The sites most commonly obstructed are at the
union of the vertebral arteries to form the
basilar artery and the upper bifurcation of the
basilar artery into the posterior cerebral
arteries.

36. Aetiology
 The most commonly recognized source
for cerebral embolism is the heart.
However, identification of a potential
cardiac source does not prove embolism,
especially if there is coexistent
atherosclerosis or if the cardiac lesion is
of uncertain clinical significance.
 Cardiac conditions predisposing to
cerebral embolism include atrial
fibrillation, valvular disorders, and the
cardiomyopathies.

37. Intracerebral Haemorrhage
 This is usually due to bursting of Charcot-
Buchald aneurysm of lenticulostriate or
thalamostriate arteries causing putaminal
or thalamic haemorrhage
 Patients are drowsy or comatose due to
raised intracranial pressure
 There may be cardiac arrhythmias from
excessive sympathetic discharge.

38. Management of stroke
Ischaemic and haemorrhagic

39. Issues in acute stroke
management
 Stroke affect both old and young
 It can be treated successfully
 Urgent interventions to limit brain
damage principle:
-give intervention that help
-know when to intervene
-avoid ineffective or dangerous
treatment

40. Protocol for acute stroke
management
 Resuscitation to support vital
functions
 Stroke subtypes identification
 Etiologic diagnosis
 Prevention of worsening
 Prevention of complications
 Early rehabilitation

41. Pre-hospital evaluation: Cincinnati Scale
 Have patient show his/her teeth:
-normal is both side of face are equal
-abnormal if one side does not move
 Patients closes eyes and raise arms:
-normal if both arms are raised
-abnormal if one arm sags or is paralyzed
 Speech:
-Fluent if normal
-abnormal if slurred, inappropriate, absent

42. Clinical evaluation
 History of stroke: time of symptoms onset,
evolution of symptoms, headache, chest pain at
onset, convulsions
 Past medical history: hypertension, recent stroke,
diabetic crisis, transient ischemic attacks.
 Surgical history: recent surgical procedure
 Medication: anticoagulant
 Neurological examination should focus on
identifying signs of lateralised hemispheric or
brainstem dysfunctions consistent with focal
cerebral or brainstem ischemia.
 The National Institute of Health (NIH) stroke scale
is a validated 15 item scale which is utilized to
access severity of stroke using the key
components of the standard Neurological
examination of stroke patients.

43. Emergency investigations
 The goals for the diagnostic evaluation are to establish
the diagnosis of ischemic stroke as a cause of the
patient's symptoms and to determine the underlying
cause of the event.
 Blood sugar is mandatory to exclude hypoglycemia or
diagnose diabetes mellitus
 Electrocardiogram to determine cardiac arrhythmias
 Full blood count to detect Polycythaemia, ESR to
detect endocarditis, clotting studies for
hypercoagulable states
 Echocardiography to detect presence of valve disease
and intra-cardiac clot
 Brain imaging (CT or MRI) is the only reliable means
to differentiate between ischemic and heamorrhagic
stroke. CT is sensitive to the intracranial blood, is
readily available though expensive. The appearance of
ischemic changes on CT evolves over time.

44. Emergency treatment 1: Neuroscience
of cerebral ischemia
 Cerebral blood flow is 750 mls per minute or 50
mls per 100 g. of brain tissue and this is kept
constant by phenomenon of auto-regulation.
 Following stroke, auto-regulation is lost and
cerebral blood flow thus depends of blood
pressure increasing or decreasing with blood
pressure
 Following occlusion of cerebral blood vessel, there
is attempt at collateral circulation: inner core of
infarct has CBF 10 mls/110g/min, the penumbra
area 10-20mls/100g/min.
 The penumbra tissue lose electrical activity and
can be salvaged if blood flow is restored by
increase in blood pressure, or rehydration, during
window period. Reduction in BP or dehydration
will worsen ischemia

45. Emergency treatment 2:
General measures
 Adequate hydration with isotonic fluid
(saline) at least 3 litres per day
 Give airway support and adequate oxygen
in comatose patients with brainstem
stroke
 Aspirin should be give at a dose of 300
mg daily starting from the first 24 hours
 In patients with dense hemiplegia,
subcutaneous heparin at a dose of
5000i.u. 8 hrly or 8000 i.u 12 hrly should
be given to prevent deep vein thrombosis
 Early physiotherapy should be initiated

46. Emergency treatment 3:
specific measures
 High blood pressure should not be treated.
BP usually spontanously fall within 24
hours. Persistent high systolic b.p above
220 or diastolic above 120 or if heart is
failing should be treated with labetalol or
atenolol.
 High blood glucose increases morbidity and
mortality and should be aggressively
treated.
 High temperature damages brain in stroke
and should be aggressively treated with
antipyretics and relevant antibiotics
 Seizures should be treated with phenytoin.

47. Medical complications of ischemic
stroke
 Complications of immobility: deep vein
thrombosis/pulmonary embolism, falls, pressure
sores or ulceration
 Infections: chest infections, urinary tract
infections, other infections
 Malnutrition: dysphagia, dehydration
 Pain: shoulder pain (subluxation in paretic limb),
headache, muscular pain
 Neuropsychiatric disturbances: depression, acute
confusional state
 Miscellaneous: cardiac arrhythmias, myocardial
infarction, gastrointestinal bleed, constipation.

48.  Cardiac arrhythmias: this occurs in the
first few days of stroke due to
sympathetic over activity. it should be
detected by ECG and treated with beta
blockers. Cardiac arrhythmias are
particularly common in haemorrhagic
stroke.
 Heart failure: a serious complication.
Heart failure should be treated.

49. Deep vein thrombosis and pulmonary
embolism
 Clinically detected deep venous thrombosis occurs
in approximately every 200 patients with ischemic
stroke
 Prophylaxis with subcutaneous heparin 5000 units
subcutaneously twice daily reduces the rate of
deep venous thrombosis and should be
considered for all non-ambulatory patients.
 Among patients with an NIH stroke scale score of
14 or more, the prevalence of venous
thromboembolism was 16%
 Deep vein thrombosis occur in stroke the
predisposing factors being immobilization and
dehydration.

50. Pressure sores and ulceration
 Early mobilization of neurologically stable patient
can help reduce the risk of pressure sores and
ulceration
 For patients who cannot be mobilized, routine
assessment for skin breakdown particularly in
dependent areas is recommended.
 Steps that may reduce this complication include
frequent inspection of the skin, skin cleansing,
frequent turning, use of special mattresses and
protective dressings, maintaining adequate
nutritional status, and early mobilization.
 Frequent turning can help to minimize the risk of
decubitus ulcers. Skin should be dry and free of
moisture particularly in patients with urinary
incontinence. Antibiotics and debridement may be
necessary in cases of severe skin breakdown

51. Infections : pneumonia and urinary
tracts infections
 Post stroke infections are common in the first five
days of admission and is associated with poor
prognosis
 Patients with dysphagia are particularly at the risk of
aspiration pneumonia
 Appropriate evaluation of swallowing functions and
modification of oral intake may prevent many cases
of pneumonia.
 General measure to prevent pneumonia include
airway suction and aggressive pulmonary toilet.
Mobilization to change position frequently also help

52. Infections : pneumonia and urinary
tracts infections
 The use of prophylactic antibiotics after
stroke to prevent infection is not supported
by evidence. Prompt antibiotics is however
required in those who develop infections
 Urinary tract infection is a common
complications in stroke patients on
admission, as a result of use of catheter
 Urine should be acidified by giving a large
dose of vitamin C to acidify the urine and
discourage the growth of proteus or
pseudomonas.

53. Dysphagia
 High risk presentation for dysphagia: brainstem
stroke, impaired consciousness, difficulties or
inability to sit upright, facial weakness, shortness
of breath, hoarse voice, weak cough
 Prior to allowing oral intake a formal screening of
swallowing functions should be performed
 High risk patients and those who fail the 3-oz
water test should be maintained on nil by mouth
 Patients who cannot swallow should use a naso-
gastric tube for feeding. In some patient, a
gastostomy tube may be required
 Good pulmonary hygiene, including chest
percussion, suctioning, drainage, and frequent
turning is recommended for bedridden patients.

54. Neurological complications of stroke
 Cerebral oedema
 Mass effect and herniation
 Haemorrhagic transformation
 Seizures
 Progressive ischemia
 Recurrent stroke
 Measurable deterioration of functions can
occur in patients hospitalized for
ischemic stroke and is usually attributed
to progressive stroke, raised intracranial
pressure, recurrent cerebral ischemia and

55. Neurological complications of stroke
 Haemorrhagic infarction: this is common
in embolic infarction. To prevent this,
patients with embolic infarction should
not be treated with heparin or with any
form of anticoagulant in the first 30 days.
 Seizures can lead to deterioration of
symptoms and should therefore be
promptly treated with phenytoin
 Expanding haemotoma in intracerebral
haemorrhage may be treated with
mannitol the same way as cerebral
oedema

56. Cerebral oedema and mass effects
 Large infarction involving the cerebral hemisphere
and cerebellum may result in space occupying
mass effect due to cerebral oedema
 Therapy for cerebral oedema:
 Mannitol : osmotic agent facilitating movement of
fluid in the interstitial/intracellular compartment
across the blood brain barrier. 20% mannitol
Ig/kg initial bolus and maintenance of 0.5g/kg
 Cerebral oedema usually occurs in massive
cerebral infarction or lacunar infarction and
should be treated with 20% mannitol
supplemented by frusemide