Stroke, a type of cerebrovascular disease, was previously known as

cerebrovascular accident (CVA). Stroke is the acute loss of

perfusion to the vascular territory of the brain, resulting in a rapid
and corresponding loss of neurologic function. Stroke signs and
symptoms include weakness, sensory deficit, and difficulties with
language. Stroke treatment should emphasize risk assessment,
prevention, management, monitoring according to the latest stroke
guidelines, and consideration of special circumstances

For patients with

ischemic stroke or TIA with
persistent or paroxysmal
(intermittent) AF, anticoagulation Class
with adjusted-dose warfarin I,
(target INR, 2.5; range, 2.0-3.0) is Level
recommended. A
Class
In patients unable to take oral I,
anticoagulants, aspirin 325 mg/d is Level
F recommended. A
Acute MI and LV For patients with an Class
thrombus ischemic stroke caused by an IIa,
acute MI in whom LV mural Level
thrombus is identified by B
echocardiography or another form
of cardiac imaging, oral
anticoagulation is reasonable,
aiming for an INR of 2.0 to 3.0 for
at least 3 months and up to 1
year.
 Aspirin should be used
concurrently for the ischemic CAD
patient during oral anticoagulant Class
therapy in doses up to 162 mg/d, IIa,
preferably in the enteric-coated Level
form. A
For patients with
ischemic stroke or TIA who have
dilated cardiomyopathy, either
warfarin (INR, 2.0 to 3.0) or Class
antiplatelet therapy may be IIb,
considered for prevention of Level
Cardiomyopathy recurrent events. C
Valvular heart disease
For patients with
ischemic stroke or TIA who have
rheumatic mitral valve disease,
whether or not AF is present, long- Class
term warfarin therapy is IIa,
reasonable, with a target INR of Level
2.5 (range, 2.0-3.0). C
Antiplatelet agents should not be Class
routinely added to warfarin in the III,
interest of avoiding additional Level
bleeding risk. C
For ischemic stroke or TIA
patients with rheumatic mitral
valve disease, whether or not AF is
present, who have a recurrent Class
embolism while receiving warfarin, IIa,
Rheumatic mitral adding aspirin (81 mg/d) is Level
valve disease suggested. C
 For patients with MVP who have Class
ischemic stroke or TIAs, long- IIa,
term antiplatelet therapy is Level
MVP reasonable. C
For patients with
ischemic stroke or TIA and MAC Class
not documented to be calcific, IIb,
antiplatelet therapy may be Level
considered. C
Among patients with mitral Class
regurgitation resulting from MAC IIb,
without AF, antiplatelet or warfarin Level
MAC therapy may be considered. C
For patients with
ischemic stroke or TIA and aortic Class
valve disease who do not have AF, IIa,
Aortic valve antiplatelet therapy may be Level
disease considered. C
Prosthetic heart For patients with
valves ischemic stroke or TIA who have
modern mechanical prosthetic Class
heart valves, oral anticoagulants I,
are recommended, with an INR Level
target of 3.0 (range, 2.5-3.5). B
For patients with mechanical Class
prosthetic heart valves who have IIa,
an ischemic stroke or systemic Level
embolism despite adequate B
therapy with oral anticoagulants,
aspirin 75 to 100 mg/d, in addition
to oral anticoagulants, and
maintenance of the INR at a target
 of 3.0 (range, 2.5-3.5) is
reasonable.
For patients with
ischemic stroke or TIA who have
bioprosthetic heart valves with no Class
other source of thromboembolism, IIb,
anticoagulation with warfarin (INR, Level
2.0-3.0) may be considered. C
Recommendations for Antithrombotic Therapy for
Noncardioembolic Stroke or TIA (Oral Anticoagulant
and Antiplatelet Therapies)
Class/Level
Recommendation of Evidence
For patients with noncardioembolic
ischemic stroke or TIA, antiplatelet agents
rather than oral anticoagulation are
recommended to reduce the risk of
recurrent stroke and other cardiovascular Class I, Level
events. A
Aspirin (50 to 325 mg/d) monotherapy, the
combination of aspirin and extended-release
dipyridamole, and clopidogrel monotherapy
are all acceptable options for initial Class I, Level
therapy.*(2008 Addendum) A
The combination of aspirin and extended-
release dipyridamole is recommended over Class I, Level
aspirin alone. (2008 Addendum) B
Clopidogrel may be considered over aspirin
alone on the basis of direct-comparison Class IIb,
trials. Level B
For patients allergic to aspirin, clopidogrel is Class IIa,
reasonable. Level B
 Class/Level
Recommendation of Evidence
The addition of aspirin to clopidogrel
increases the risk of hemorrhage.
Combination therapy of aspirin and
clopidogrel is not routinely recommended
for ischemic stroke or TIA patients unless
they have a specific indication for this
therapy (i.e., coronary stent or acute Class III,
coronary syndrome). Level A
*For patients who have an ischemic cerebrovascular event while taking
aspirin, there is no evidence that increasing the dose of aspirin
provides additional benefit. Although alternative antiplatelet agents are
often considered for noncardioembolic patients, no single agent or
combination has been well studied in patients who have had an event
while receiving aspirin.
Recommendations for Stroke Patients With Other
Specific Conditions
Class/Lev
el of
Risk Factor Recommendation Evidence
Arterial dissection For patients with
ischemic stroke or TIA
and arterial dissection,
warfarin for 3 to 6
months or antiplatelet Class IIa,
agents are reasonable. Level B
Beyond 3 to 6 months, Class IIb,
long-term antiplatelet Level C
therapy is reasonable for
most ischemic stroke or
TIA patients.
Anticoagulant therapy
 Class/Lev
el of
Risk Factor Recommendation Evidence
beyond 3 to 6 months
may be considered
among patients with
recurrent ischemic
events.
For patients who have
definite recurrent
ischemic events despite
antithrombotic therapy,
endovascular therapy
(stenting) may be Class IIb,
considered. Level C
Patients who fail or are
not candidates for
endovascular therapy
may be considered for Class IIb,
surgical treatment. Level C
Patent foramen ovale For patients with an
ischemic stroke or TIA
and a PFO, antiplatelet
therapy is reasonable to
prevent a recurrent Class IIa,
event. Level B
Warfarin is reasonable Class IIa,
for high-risk patients Level C
who have other
indications for oral
anticoagulation such as
those with an underlying
 Class/Lev
el of
Risk Factor Recommendation Evidence
hypercoagulable state or
evidence of venous
thrombosis.
Insufficient data exist to
make a recommendation
about PFO closure in
patients with a
first stroke and a PFO.
PFO closure may be
considered for patients
with recurrent
cryptogenic stroke desp Class IIb,
ite medical therapy. Level C
For patients with an
ischemic stroke or TIA
and
hyperhomocysteinemia
(levels >10 micromol/L),
daily standard
multivitamin
preparations are
reasonable to reduce the
level of homocysteine,
given their safety and
low cost. However, there
is no evidence that
reducing homocysteine
levels will lead to a
Hyperhomocysteine reduction Class I,
mia ofstroke occurrence. Level A
 Class/Lev
el of
Risk Factor Recommendation Evidence
Hypercoagulable states
Patients with an
ischemic stroke or TIA
with an established
inherited thrombophilia
should be evaluated for
deep venous
thrombosis, which is an
indication for short- or
long-term anticoagulant
therapy, depending on
the clinical and
hematologic Class IIa,
circumstances. Level A
Patients should be fully
evaluated for alternative Class IIa,
mechanisms of stroke. Level C
In the absence of
venous thrombosis,
long-term
anticoagulation or
antiplatelet therapy is
reasonable.
Patients with a history of
recurrent thrombotic
events may be
Inherited considered for long-term Class IIb,
thrombophilias anticoagulation. Level C
Antiphospholipid For cases of cryptogenic Class IIa,
 Class/Lev
el of
Risk Factor Recommendation Evidence
ischemic stroke or TIA
and positive APL
antibodies, antiplatelet
therapy is reasonable. Level B
For patients with
ischemic stroke or TIA
who meet the criteria for
the APL antibody
syndrome with venous
and arterial occlusive
disease in multiple
organs, miscarriages,
and livedo reticularis,
oral anticoagulation with
a target INR of 2 to 3 is Class IIa,
antibody syndrome reasonable. Level B
Sickle-cell disease For adults with SCD and
ischemic stroke or TIA,
general treatment
recommendations cited
above are applicable
with regard to the
control of risk factors
and use of antiplatelet Class IIa,
agents. Level B
Additional therapies that Class IIb,
may be added include Level C
regular blood transfusion
to reduce Hb S to <30 to
50% of total Hb,
 Class/Lev
el of
Risk Factor Recommendation Evidence
hydroxyurea, or bypass
surgery in cases of
advanced occlusive
disease.
For patients with
cerebral venous sinus
thrombosis, UFH or
LMWH is reasonable
even in the presence of Class IIa,
hemorrhagic infarction. Level B
Continuation of
anticoagulation with an
oral anticoagulant agent
is reasonable for 3 to 6
Cerebral venous months, followed by Class IIa,
sinus thrombosis antiplatelet therapy. Level C
Pregnancy For pregnant women Class IIb,
with an Level C
ischemic stroke or TIA
and high-risk
thromboembolic
conditions such as
known coagulopathy or
mechanical heart valves,
the following options
may be considered:
• Adjusted-dose UFH
throughout
pregnancy such as a
subcutaneous dose
 Class/Lev
el of
Risk Factor Recommendation Evidence
every 12 h with
APTT monitoring
• Adjusted-dose
LMWH with factor
Xa monitoring
throughout
pregnancy
• UFH or LMWH until
week 13, followed
by warfarin until the
middle of the third
trimester, when
UFH or LMWH is
then reinstituted
until delivery.
Pregnant women with
lower-risk conditions
may be considered for
treatment with UFH or
LMWH in the first
trimester, followed by
low-dose aspirin for the
remainder of the Class IIb,
pregnancy. Level C
For women
with stroke or TIA,
postmenopausal HRT is Class III,
Postmenopausal HRT not recommended. Level A
Cerebral hemorrhage For patients who Class III,
develop an ICH, SAH, or Level B
 Class/Lev
el of
Risk Factor Recommendation Evidence
SDH, all anticoagulants
and antiplatelets should
be discontinued during
the acute period for at
least 1 to 2 weeks after
the hemorrhage and the
anticoagulant effect
reversed immediately
with appropriate agents
(i.e., vitamin K, FFP).
For patients who require
anticoagulation soon
after a cerebral
hemorrhage,
intravenous heparin may
be safer than oral
anticoagulation. Oral
anticoagulants may be
resumed after 3 to 4
weeks, with rigorous
monitoring and
maintenance of INRs in
the lower end of the Class IIb,
therapeutic range. Level C
Special circumstances:
Anticoagulation should Class III,
not be resumed after an Level C
SAH until the ruptured
aneurysm is definitively
 Class/Lev
el of
Risk Factor Recommendation Evidence
secured.

Patients with lobar ICHs

or microbleeds and
suspected CAA on MRI
may be at a higher risk
for recurrent ICH if
anticoagulation needs to Class IIb,
be resumed. Level C
For patients with
hemorrhagic infarction,
anticoagulation may be
continued, depending on
the specific clinical
scenario and underlying
indication for
anticoagulant therapy.

Recommendations for Treatable Vascular Risk

Factors
Class/Level
Risk Factor Recommendation of Evidence
Hypertension Antihypertensive treatment is Class I, Level
recommended for prevention of A
recurrent stroke and other
vascular events in persons who
 Class/Level
Risk Factor Recommendation of Evidence
have had an
ischemic stroke and are
beyond the hyperacute period.
Because this benefit extends to
persons with and without a
history of hypertension, this
recommendation should be
considered for all
ischemic stroke and TIA Class IIa,
patients. Level B
An absolute target BP Level
and reduction are uncertain
and should be individualized,
but benefit has been associated
with an average reduction of
approximately 10/5 mm Hg
and normal BP levels have
been defined as <120/80 by Class IIa,
JNC-7. Level B
Several lifestyle modifications
have been associated with BP
reductions and should be
included as part of a
comprehensive approach Class IIb,
antihypertensive therapy. Level C
Optimal drug regimen remains Class I, Level
uncertain; however, available A
data support the use of
diuretics and the combination
of diuretics and an ACEI.
 Class/Level
Risk Factor Recommendation of Evidence
Choice of specific drugs and
targets should be individualized
on the basis of reviewed data
and consideration, as well as
specific patient characteristics
(e.g., extracranial
cerebrovascular occlusive
disease, renal impairment,
cardiac disease, and DM).
Diabetes More rigorous control of blood
pressure and lipids should be
considered in patients with Class IIa,
diabetes. Level B
Although all major classes of
antihypertensives are suitable
for the control of BP, most
patients will require >1 agent.
ACEIs and ARBs are more
effective in reducing the
progression of renal disease
and are recommended as first-
choice medications for patients Class I, Level
with DM. A
Glucose control is Class I, Level
recommended to near- A
normoglycemic levels among
diabetics with
ischemic stroke or TIA to
reduce microvascular
complications.
 Class/Level
Risk Factor Recommendation of Evidence
The goal for Hb A1c should Class IIa,
be <7%. Level B
Cholesterol Ischemic stroke or TIA
patients with elevated
cholesterol, comorbid CAD, or
evidence of an atherosclerotic
origin should be managed
according to NCEP III
guidelines, which include
lifestyle modification, dietary
guidelines, and medication Class I, Level
recommendations. A
Statin agents are
recommended, and the target
goal for cholesterol lowering for
those with CHD or symptomatic
atherosclerotic disease is an
LDL-C of <100 mg/dL. An LDL-
C <70 mg/dL is recommended
for very-high-risk persons with Class I, Level
multiple risk factors. A
On the basis of the SPARCL Class I, Level
trial, administration of statin B
therapy with intensive lipid-
lowering effects is
recommended for patients with
atherosclerotic
ischemic strokeor TIA and
without known CHD to reduce
the risk of stroke and
cardiovascular events. (2008
 Class/Level
Risk Factor Recommendation of Evidence
Addendum)
Ischemic stroke or TIA
patients with low HDL
cholesterol may be considered
for treatment with niacin or Class IIb,
gemfibrozil. Level B
Recommendations for Modifiable Behavioral Risk
Factors
Risk Class/Level
Factor Recommendation of Evidence
All ischemic stroke or TIA patients
who have smoked in the past year
should be strongly encouraged not Class I, Level
to smoke. C
Class IIa,
Avoid environmental smoke. Level C
Counseling, nicotine products, and
oral smoking cessation
medications have been found to be Class IIa,
Smoking effective for smokers. Level B
Patients with prior
ischemic stroke or TIA who are
heavy drinkers should eliminate or
reduce their consumption of Class I, Level
alcohol. A
Light to moderate levels of <2
drinks per day for men and 1 drink
per day for nonpregnant women Class IIb,
Alcohol may be considered. Level C
 Risk Class/Level
Factor Recommendation of Evidence
Weight reduction may be
considered for all overweight
ischemic stroke or TIA patients to
maintain the goal of a BMI of 18.5
to 24.9 kg/m2 and a waist
circumference of <35 inches for
women and <40 inches for men.
Clinicians should encourage weight
management through an
appropriate balance of caloric
intake, physical activity, and Class IIb,
Obesity behavioral counseling. Level C
For those with ischemic stroke or
TIA who are capable of engaging
in physical activity, at least 30
minutes of moderate-intensity
physical exercise most days may
be considered to reduce risk
factors and comorbid conditions
that increase the likelihood of
recurrence of stroke. For those
with disability after
ischemic stroke, a supervised
Physical therapeutic exercise regimen is Class IIb,
activity recommended. Level C
Recommendations for Interventional Approaches to
Patients With Stroke Caused by Large-Artery
Atherosclerotic Disease
 Class/Level
Risk Factor Recommendation of Evidence
Extracranial For patients with recent TIA
carotid disease or ischemic stroke within
the last 6 months and
ipsilateral severe (70 to
99%) carotid artery stenosis,
CEA is recommended by a
surgeon with a perioperative
morbidity and mortality of Class I, Level
<6%. A
For patients with recent TIA
or ischemic stroke and
ipsilateral moderate (50 to
69%) carotid stenosis, CEA
is recommended, depending
on patient-specific factors
such as age, gender,
comorbidities, and severity Class I, Level
of initial symptoms. A
When degree of stenosis is
<50%, there is no indication Class III,
for CEA. Level A
When CEA is indicated,
surgery within 2 weeks
rather than delayed surgery Class IIa,
is suggested. Level B
Among patients with Class IIb,
symptomatic severe stenosis Level B
(>70%) in whom the
stenosis is difficult to access
surgically, medical conditions
 Class/Level
Risk Factor Recommendation of Evidence
are present that greatly
increase the risk for surgery,
or when other specific
circumstances exist such as
radiation-induced stenosis or
restenosis after CEA, CAS is
not inferior to
endarterectomy and may be
considered.
CAS is reasonable when
performed by operators with
established periprocedural
morbidity and mortality rates
of 4 to 6%, similar to that
observed in trials of CEA and Class IIa,
CAS. Level B
Among patients with
symptomatic carotid
occlusion, EC/IC bypass
surgery is not routinely Class III,
recommended. Level A
Endovascular treatment of
patients with symptomatic
extracranial vertebral
stenosis may be considered
when patients are having
symptoms despite medical
Extracranial therapies (antithrombotics,
vertebrobasilar statins, and other treatments Class IIb,
disease for risk factors). Level C
 Class/Level
Risk Factor Recommendation of Evidence
The usefulness of
endovascular therapy
(angioplasty and/or stent
placement) is uncertain for
patients with
hemodynamically significant
intracranial stenoses who
have symptoms despite
medical therapies
(antithrombotics, statins,
and other treatments for risk
Intracranial factors) and is considered
arterial disease investigational.

Introduction
Background
Stroke is characterized by the sudden loss of blood circulation to an
area of the brain, resulting in a corresponding loss of neurologic
function. Also previously called cerebrovascular accident (CVA) or
stroke syndrome, stroke is a nonspecific term encompassing a
heterogeneous group of pathophysiologic causes, including
thrombosis, embolism, and hemorrhage.

Click here to view a slideshow on Acute Stroke.

Strokes are broadly classified as either hemorrhagic or ischemic.

Acute ischemic stroke refers to stroke caused by thrombosis or
embolism and is more common than hemorrhagic stroke. Prior
literature indicates that only 8-18% of strokes were hemorrhagic.
However, a recent retrospective review from a stroke center found
that 40.9% of 757 strokes were hemorrhagic. However, the authors
state that the increased percentage of hemorrhagic stroke may be
due to improvement of CT scan availability and implementation
unmasking a previous underestimation of the actual percentage, or
it may be due to an increase in therapeutic use of antiplatelet
agents and warfarin causing an increase in the incidence of
hemorrhage.1

Emergency physicians (EPs) play a central role in the initial

evaluation and management of patients with acute stroke. In 1992,
a National Institute of Neurologic Disorders and Stroke (NINDS) t-
PA Pilot Trial succeeded at enrolling patients within 90 minutes,
which led to the NINDS requirement that investigators from
emergency medicine be involved in the larger randomized trial. The
NINDS recombinant tissue-type plasminogen activator (rt-PA)
stroke study group first reported that the early administration of rt-
PA benefited carefully selected patients with acute ischemic stroke.2
The trial had a positive outcome leading to the long-standing goal of
t-PA administration within a 3-hour window for a patient deemed
likely to benefit from thrombolytic intervention. This window has
recently been expanded after recent evidence suggested benefit out
to 4.5 hours. The collaboration between emergency physicians and
neurologists was visionary and enabled the early enrollment of
patients, which was an integral component of the positive results.
Encouraged by this breakthrough study and the subsequent
approval of t-PA for use in acute ischemic stroke by the US Food
and Drug Administration (FDA), many medical professionals now
newly consider acute ischemic stroke to be a medical emergency—
one that may be amenable to treatment.

Building on the success of the NINDS trial and other studies, the
European Cooperative Acute Stroke Study III (ECASS III) examined
the use of thrombolytic therapy between 3 and 4.5 hours after the
onset of symptoms.Thrombolytic therapy was again found to be
efficacious in improving neurologic outcomes, suggesting a wider
time window for the administration of thrombolytics.3 Based on this
and other data, in May 2009, the American Heart Association and
the American Stroke Association guidelines for the administration of
rt-PA were revised to expand the treatment window from 3 to 4.5
hours.4 This indication has not yet been FDA approved.

Since EPs play a central role in the initial evaluation and treatment
of patients with acute ischemic stroke, our understanding of its
pathophysiology, clinical presentation, and ED evaluation is
essential. The EP also must be completely familiar with the entire
therapeutic armamentarium currently available to treat acute
ischemic stroke, which includes supportive care, treatment of
neurologic complications, antiplatelet therapy, glycemic control,
blood pressure control, prevention of hyperthermia,
and thrombolytic therapy.

In recent years, significant advances have also been made in stroke

prevention, supportive care, and rehabilitation. With emerging
evidence that the brief counsel of emergency physicians may
impact primary and secondary prevention of disease processes, the
emergency medicine specialty is also challenged to be vigilant in
utilizing "teachable moments" or "brief negotiated interviews" to
impact patient education, awareness, and compliance with
established preventative treatments. Overall, when the direct costs
(care and treatment) and the indirect costs (lost productivity) of
strokes are considered together, the cost to US society is $43.3
billion per year.5

Pathophysiology
On the macroscopic level, ischemic stroke most often is caused by
extracranial embolism or intracranial thrombosis, but it may also be
caused by decreased cerebral blood flow. On the cellular level, any
process that disrupts blood flow to a portion of the brain unleashes
an ischemic cascade, leading to the death of neurons and cerebral
infarction. Understanding this chain of events is important for
understanding current therapeutic approaches.

Embolism

Emboli may arise from the heart, the extracranial arteries or, rarely,
the right-sided circulation (paradoxical emboli) with subsequent
passage through a patent foramen ovale. The sources of
cardiogenic emboli include valvular thrombi (eg, in mitral
stenosis, endocarditis, prosthetic valve), mural thrombi (eg,
in myocardial infarction [MI], atrial fibrillation [AF], dilated
cardiomyopathy, severe congestive heart failure [CHF]), and atrial
myxoma. MI is associated with a 2-3% incidence of embolic stroke,
of which 85% occur in the first month after MI.6

Thrombosis
Thrombotic stroke can be divided into large vessel, including the
carotid artery system, or small vessel comprising the intracerebral
arteries, including the branches of the Circle of Willis and the
posterior circulation. The most common sites of thrombotic
occlusion are cerebral artery branch points, especially in the
distribution of the internal carotid artery. Arterial stenosis can cause
turbulent blood flow, which can increase risk for thrombus formation,
atherosclerosis (ie, ulcerated plaques), and platelet adherence; all
cause the formation of blood clots that either embolize or occlude
the artery.

Less common causes of thrombosis include polycythemia, sickle

cell anemia, protein C deficiency, fibromuscular dysplasia of the
cerebral arteries, and prolonged vasoconstriction from migraine
headache disorders. Any process that causes dissection of the
cerebral arteries also can cause thrombotic stroke (eg, trauma,
thoracic aortic dissection, arteritis). Occasionally, hypoperfusion
distal to a stenotic or occluded artery or hypoperfusion of a
vulnerable watershed region between two cerebral arterial territories
can cause ischemic stroke.

Flow disturbances

Stroke symptoms can result from inadequate cerebral blood flow

due to decreased blood pressure (and specifically decreased
cerebral perfusion pressure) or due to hematologic hyperviscosity
due to sickle cell disease or other hematologic illnesses such as
multiple myeloma and polycythemia vera. In these instances,
cerebral injury may occur in the presence of damage to other organ
systems.
Ischemic cascade

Within seconds to minutes of the loss of perfusion to a portion of the

brain, an ischemic cascade is unleashed that, if left unchecked,
causes a central area of irreversible infarction surrounded by an
area of potentially reversible ischemic penumbra.

On the cellular level, the ischemic neuron becomes depolarized as

ATP is depleted and membrane ion-transport systems fail. The
resulting influx of calcium leads to the release of a number of
neurotransmitters, including large quantities of glutamate, which, in
turn, activates N -methyl-D-aspartate (NMDA) and other excitatory
receptors on other neurons. These neurons then become
depolarized, causing further calcium influx, further glutamate
release, and local amplification of the initial ischemic insult. This
massive calcium influx also activates various degradative enzymes,
leading to the destruction of the cell membrane and other essential
neuronal structures.7

Free radicals, arachidonic acid, and nitric oxide are generated by

this process, which leads to further neuronal damage. Within hours
to days after a stroke, specific genes are activated, leading to the
formation of cytokines and other factors that, in turn, cause further
inflammation and microcirculatory compromise.7 Ultimately, the
ischemic penumbra is consumed by these progressive insults,
coalescing with the infarcted core, often within hours of the onset of
the stroke.

The central goal of therapy in acute ischemic stroke is to preserve

the area of oligemia in the ischemic penumbra. The area of oligemia
can be preserved by limiting the severity of ischemic injury (ie,
neuronal protection) or by reducing the duration of ischemia (ie,
restoring blood flow to the compromised area).

The ischemic cascade offers many points at which such

interventions could be attempted. Multiple strategies and
interventions for blocking this cascade are currently under
investigation. The timing of the restoration of cerebral blood flow
appears to be a critical factor. Time also may prove to be a key
factor in neuronal protection. Although still being studied,
neuroprotective agents, which block the earliest stages of the
ischemic cascade (eg, glutamate receptor antagonists, calcium
channel blockers), are expected to be effective only in the proximal
phases of presentation.

Frequency
United States

Incidence for first-time stroke is more than 700,000 per year, of

which 20% of these patients will die within the first year after stroke.
At current trends, this number is projected to jump to 1 million per
year by the year 2050.8

International

Global incidence of stroke is unknown.

Mortality/Morbidity
Stroke is the third leading cause of death and the leading cause of
disability in the United States.9
 • Cerebrovascular disease was the second leading cause of
death worldwide in 1990, killing more than 4.3 million people.10
• Cerebrovascular disease was also the fifth leading cause of
lost productivity, as measured by disability-adjusted life years
(DALYs). DALYs include years of productivity lost to either
death or varying degrees of disability. In 1990, cerebrovascular
disease caused 38.5 million DALYs throughout the world.11

Sex
Men are at higher risk for stroke than women. Additionally, women
seem to respond better than men to interventions such as rt-PA.

Age
Although stroke often is considered a disease of elderly
persons, one third of strokes occur in persons younger than 65
years.8

Clinical
History

• Stroke should be considered in any patient presenting with an

acute neurologic deficit (focal or global) or altered level of
consciousness.
• No historical feature distinguishes ischemic from hemorrhagic
stroke, although nausea, vomiting, headache, and change in
level of consciousness are more common in hemorrhagic
strokes.
• Common symptoms of stroke include abrupt onset of
hemiparesis, monoparesis, or quadriparesis; monocular or
 binocular visual loss; visual field deficits; diplopia; dysarthria;
ataxia; vertigo; aphasia; or sudden decrease in the level of
consciousness.
• Although such symptoms can occur alone, they are more likely
to occur in combination.
• Establishing the time of onset of these symptoms is of
paramount importance when considering patients for possible
thrombolytic therapy. An essential question is, "When was the
patient last seen normal?" It is advisable for emergency
clinicians to rapidly enlist the assistance of family members or
relatives to establish time of onset and to identify other
pertinent components of the patient's history of presentation.
The median time from symptom onset to ED presentation
ranges from 4-24 hours in the United States.12
• Multiple factors contribute to delays in seeking care for
symptoms of stroke.
o Many strokes occur while patients are sleeping (also

known as "wake-up" stroke) and are not discovered until

the patient wakes.
o Stroke can leave some patients too incapacitated to call

for help.
o Occasionally, a stroke goes unrecognized by the patient

or their caregivers.8,13
• Stroke mimics commonly confound the clinical diagnosis of
stroke. One study reported that 19% of patients diagnosed
with acute ischemic stroke by neurologists before cranial CT
scanning actually had noncerebrovascular causes for their
symptoms. The most frequent stroke mimics include seizure
(17%); systemic infection (17%); brain tumor (15%); toxic-
metabolic cause, such as hyponatremia (13%); and positional
 vertigo (6%). Miscellaneous disorders mimicking stroke include
syncope, trauma, subdural hematoma, herpes encephalitis,
transient global amnesia, dementia, demyelinating disease,
myasthenia gravis, parkinsonism, hypertensive
encephalopathy, and conversion disorders. A critical
masquerading metabolic derangement not to be missed by
providers is hypoglycemia.14,15

Physical

• The goals of the physical examination include detecting

extracranial causes of stroke symptoms, distinguishing stroke
from stroke mimics, determining and documenting for future
comparison the degree of deficit, and localizing the lesion.
• The physical examination always includes a careful head and
neck examination for signs of trauma, infection, and meningeal
irritation.
• A careful search for the cardiovascular causes of stroke
requires examination of the ocular fundi (retinopathy, emboli,
hemorrhage), heart (irregular rhythm, murmur, gallop), and
peripheral vasculature (palpation of carotid, radial, and femoral
pulses, auscultation for carotid bruit).
• Patients with a decreased level of consciousness should be
assessed to ensure that they are able to protect their airway.
• Neurologic examination
o With the availability of thrombolytic therapy for acute

ischemic stroke in selected patients, the EP must be able

to perform a brief but accurate neurologic examination on
patients with suspected stroke syndromes.
o The goals of the neurologic examination include (1)
confirming the presence of a stroke syndrome (to be
defined further by cranial CT scanning), (2) distinguishing
stroke from stroke mimics, and (3) establishing a
neurologic baseline should the patient's condition
improve or deteriorate.
o Essential components of the neurologic examination
include evaluation of mental status and the level of
consciousness, cranial nerves, motor function, sensory
function, cerebellar function, gait, and deep tendon
reflexes.
o The skull and spine also should be examined, and signs
of meningismus should be sought.
o Central facial weakness from a stroke should be
differentiated from the peripheral weakness of Bell palsy.
With peripheral lesions (Bell palsy), the patient is unable
to lift the eyebrows or wrinkle the forehead.
o The 4 principal neuroanatomic stroke syndromes are
caused by disruption of their respective cerebrovascular
distributions. Correlating the patient's neurologic deficits
with the expected site of arterial compromise may assist
in confirming the diagnosis of stroke and interpreting the
subsequent cranial CT scan.
o Middle cerebral artery (MCA) occlusion commonly
produces contralateral hemiparesis, contralateral
hypesthesia, ipsilateral hemianopsia, and gaze
preference toward the side of the lesion. Agnosia is
common, and receptive or expressive aphasia may result
if the lesion occurs in the dominant hemisphere. Neglect,
inattention, and extinction of double simultaneous
 stimulation may occur in nondominant hemisphere
lesions. Since the MCA supplies the upper extremity
motor strip, weakness of the arm and face is usually
worse than that of the lower limb.
o Anterior cerebral artery occlusions primarily affect frontal
lobe function and can result in dis-inhibition and speech
perseveration, producing primitive reflexes (eg, grasping,
sucking reflexes), altered mental status, impaired
judgment, contralateral weakness (greater in legs than
arms), contralateral cortical sensory deficits gait apraxia,
and urinary incontinence.
o Posterior cerebral artery occlusions affect vision and
thought, producing contralateral homonymous
hemianopsia, cortical blindness, visual agnosia, altered
mental status, and impaired memory.
o Vertebrobasilar artery occlusions are notoriously difficult
to detect because they cause a wide variety of cranial
nerve, cerebellar, and brainstem deficits. These include
vertigo, nystagmus, diplopia, visual field deficits,
dysphagia, dysarthria, facial hypesthesia, syncope, and
ataxia. A hallmark of posterior circulation stroke is that
there are crossed findings: ipsilateral cranial nerve
deficits and contralateral motor deficits. This is contrasted
to anterior stroke, which produces only unilateral findings.
o Lacunar strokes result from occlusion of the small,
perforating arteries of the deep subcortical areas of the
brain. The infarcts are generally from 2-20 mm in
diameter. The most common lacunar syndromes include
pure motor, pure sensory, and ataxic hemiparetic strokes.
Lacunar infarcts are often associated with partial or full
 occlusion of the parent feeding artery. Lacunar strokes
account for 13-20% of all cerebral infarctions. Lacunar
infarcts commonly occur in patients with small vessel
disease, such as diabetes and hypertension. By virtue of
their small size and well-defined subcortical location,
lacunar infarcts do not lead to impairments in cognition,
memory, speech, or level of consciousness.
o Stroke scales
 The National Institutes of Health Stroke

Scale (NIHSS) is a rapid and reproducible tool for

quantifying neurologic deficits in stroke patients and
is useful for following the patient's early course. It is
advisable to use this scale because it provides a
means of quantitatively following a patient's course
(ie, rapidly improving symptoms, or, escalation of
symptoms secondary to either a bleed or cerebral
edema).
 The NIHSS is a 42-point scale with minor strokes

usually being considered to have a score less than

5. A NIHSS score greater than 10 correlates with an
80% likelihood of visual flow deficits on
angiography. Discretion must be also be used in
assessing the magnitude of the clinical deficit; for
instance, if a patient's only deficit is being mute,
then the NIHSS score will be 3. Additionally, the
scale does not measure some deficits associated
with posterior circulation strokes (ie, vertigo,
ataxia).16

Causes
 • Risk factors
o Briefly assessing the risk factors for stroke may provide

clues as to its cause and reinforce the clinical gestalt that

clinicians may have in uncertain situations. Risk factors
for ischemic stroke include advanced age (the risk
doubles every decade), hypertension, smoking, heart
disease (coronary artery disease, left ventricular
hypertrophy, chronic atrial fibrillation), and
hypercholesterolemia. Hyperhomocysteinemia has also
been identified as an independent risk factor for all forms
of stroke.17
o Diseases associated with increased blood viscosity and

the use of oral contraceptives place patients at higher risk

for ischemic stroke.
o Previous cerebrovascular disease is a risk factor for

ischemic stroke.
• Transient ischemic attack
o Transient ischemic attack (TIA) has come to be known as

a neurologic deficit that resolves within 24 hours. Roughly

80% resolve within 60 minutes. Tissue-based definitions
are being proposed with magnetic resonance imaging.17
o TIA can result from any of the aforementioned

mechanisms of stroke. Data suggest that roughly 10% of

patients with TIA suffer stroke within 90 days and half of
these patients suffer stroke within 2 days.17,18
What are the symptoms?

Symptoms of stroke in children vary according to where the blood supply was cut off in the brain or where
the bleeding occurred. Many conditions that lead to stroke result in emboli, which are blood clots that form
in the heart, then break free and travel through the arteries to the brain. Symptoms always involve
neurological functions, and can include paralysis affecting only one side of the body (hemiplegia), general
weakness, impaired speech and verbal comprehension (dysphagia ), partial loss of vision or hearing,
unusual movements, loss of balance, and falling. Most strokes begin suddenly and symptoms develop
quickly. Less commonly, symptoms may continue to worsen for several hours. Symptoms of stroke can
also include coma or a lower level of consciousness, such as a stupor. Strokes can cause depression,
mood and behavioral disturbances, and seizures. Because stroke causes damage to the brain tissue, the
neurological damage is more likely to be permanent. However, while some brain cells die, resulting in
permanent damage, others may only be injured and may eventually recover.

How is it diagnosed?

Stroke is usually diagnosed by physical examination and a description of the symptoms. The doctor will
try to pinpoint where the brain was damaged by performing tests such as computed tomography (CT) or
magnetic resonance imaging (MRI) scans. CT and MRI scans can also help rule out a brain hemorrhage
or tumor. Your doctor will take into consideration your child’s age and any pre-existing cardiac, vascular,
or brain disorders. Your doctor will want to determine whether the stroke was ischemic or hemorrhagic.
Strokes caused by blood clots (ischemic strokes) are frequently followed by other strokes unless the
problem is corrected. If your child is having seizures, an EEG may be ordered to check brain function.
Your doctor may also order an electrocardiogram or echocardiogram if your child has a pre-existing heart
condition. Because stroke can occur if inflammation or infection narrows the blood vessels leading to the
brain, your doctor will want to rule out meningitis, encephalitis, brain abscess, bleeding inside the skull,
and migraines as causes of the stroke symptoms. Neurodegenerative disorders, such as
adrenoleukodystrophy, can also have symptoms similar to stroke.

What is the treatment?

Strokes require immediate medical treatment. At first, the goal will be to maintain and support your child’s
pulmonary, cardiovascular, and renal functions. Your child will receive oxygen and intravenous fluids.
Heart rate and rhythm and blood pressure will be monitored carefully. Specific treatment depends upon
the cause of stroke. If the stroke is in process or known to be caused by embolism, an anticoagulant like
heparin or warfarin is given to thin the blood. However, anticoagulants are not used where there is any
possibility of bleeding in the brain. Another treatment may include a small daily dose of aspirin. However,
because aspirin use in children carries with it a risk of Reye’s syndrome (a rare disorder that causes brain
inflammation), aspirin treatment should only be used when recommended by and under the supervision of
your doctor. In cases of sickle cell disease, researchers have noted some success in preventing stroke by
using periodic blood transfusions to suppress the level of circulating sickle hemoglobin to 30% or less. If
your child has had a stroke, the long-term treatment involves rehabilitation and therapy to help overcome
any lasting disabilities in language and motor skills. Children who continue to suffer from seizures may
also require anticonvulsant treatment.

Cerebrovascular disease is a group of brain dysfunctions related

to disease of the blood vessels supplying the brain. Hypertension is
the most important cause; it damages the blood vessel lining,
endothelium, exposing the underlying collagen where platelets
aggregate to initiate a repairing process which is not always
complete and perfect. Sustained hypertension permanently changes
the architecture of the blood vessels making them narrow, stiff,
deformed, uneven and more vulnerable to fluctuations in blood
pressure.
A fall in blood pressure during sleep can then lead to a marked
reduction in blood flow in the narrowed blood vessels
causing ischemic stroke in the morning. Conversely, a sudden rise
in blood pressure due to excitation during the daytime can cause
tearing of the blood vessels resulting in intracranial hemorrhage.
Cerebrovascular disease primarily affects people who are elderly or
have a history of diabetes, smoking, or ischemic heart disease. The
results of cerebrovascular disease can include a stroke, or
occasionally a hemorrhagic stroke. Ischemia or other blood vessel
dysfunctions can affect the person during a cerebrovascular
accident.

TREATMENT OF CEREBROVASCULAR DISEASE

A. GOALS OF THERAPY

1. Stroke prevention through risk-factor reduction.

2. Prevention of initial or recurrent stroke by modifying the underlying pathologic process.

3. Reduction of secondary brain damage by maintaining adequate perfusion to marginally

ischemic areas and decreasing edema.

B. TREATMENT OF TRANSIENT ISCHEMIC ATTACKS

1. Eliminate or control risk factors.

2. Education of patient regarding risk-factor reduction and signs and symptoms of TIAs
and mild stroke.

3. Surgical Interventions

a. Carotid Endarterectomy (CEA)

surgical removal of the atheromatous plaque

reserved for patients with an ulcerated lesion or clot that occludes > 70% of blood flow in
the carotid artery
may decrease risk of stroke by 60% over the two years following the procedure
vertebral endarterectomy no longer used

4. Endovascular procedures
a. Balloon Angioplasty

consists of placing a small deflated balloon in the stenosed vessel

the balloon is then inflated pressing the atheromatous plaque against the wall
has a risk of dislodging emboli that can be carried to the brain or retina

b. Stent Placement

experimental procedure
consists of placing a stainless steel coil into the vessel which then sticks to wall of artery

5. Antiplatelet Agents

a. Aspirin

1.Mechanism of Action

inhibition of platelet aggregation

decreases release of vasoactive substances from platelets
irreversible inactivation of platelet cyclooxygenase; effect lasts for the life of the platelet (5-
7 days)

2. Efficacy

ASA has shown clinically significant reductions (22-24%) in stroke risk and death in
randomized trials in patients who have experienced a previous TIA or stroke
(secondary prevention)
doses have ranged from 50 to 1500 mg/day
more recent trials have evaluated lower doses (30 to 325 mg/day); results indicate that
lower doses may be as beneficial with less adverse effects
some studies suggest that ASA is more effective in men than in women (due to small
number of women in studies??)
role in primary prevention unclear
b. Dipyridamole (PERSANTINE)

1. Mechanism of Action

weak inhibitor of platelet aggregation

inhibits platelet phosphodiesterase

2. Efficacy

clinical trials have not supported the use of dipyridamole in cerebral ischemia
no additive effect found with aspirin

c. Sulfinpyrazone (ANTURANE)

1. Mechanism of Action
reversible inhibition of cyclooxygenase

2. Efficacy

clinical trials have not supported use

d. Ticlopidine (TICLID)

1. Mechanism of Action

inhibits ADP-induced platelet aggregation

inhibits platelet aggregation induced by collagen, PAF, epinephrine and thrombin
bleeding time prolonged
minimal effect on cyclooxygenase

2. Efficacy

has been shown to reduce the incidence of stroke by approximately 22% in patients who
have experienced previous TIAs or stroke
may be more effective than aspirin with less GI effects
no gender difference seen with ticlopidine as with ASA
dosed at 500 mg/day divided into 2 doses (250 mg PO BID)
adverse effects:

1. diarrhea

2. rash

3. increased total serum cholesterol (ratio of HDL:TChol unchanged)

4. neutropenia occurred in 1-2% of patients; must monitor CBC every 2 weeks for the first
3 months of therapy

RECOMMENDATIONS

ASA has been proven to be beneficial in the secondary prevention of TIAs and in
decreasing major cerebrovascular events and death; however, the correct dosage is
still unknown.
The currently recommended dose of aspirin is 325-975 mg/day.
The role of aspirin in the primary prevention of TIAs and stroke is still unclear.
Ticlopidine has been proven to be effective in the secondary prevention of TIAs and stroke.
Due to side effects and cost, it should be reserved for those patients who fail or
cannot tolerate ASA.

6. Anticoagulation
a. Warfarin

1. no studies that prove the superiority of anticoagulants over antiplatelet agents

2. may reduce the risk of stroke in patients with a prior MI

3. may be useful in those patients who continue to be symptomatic despite antiplatelet

therapy

4. the major exception is in patients with cerebral embolism of cardiac origin

a. chronic anticoagulation with warfarin has been shown to prevent cerebrovascular events
in patients with NVAF

b. INR adjusted to between 2.0-3.0

C. Treatment of Acute Cerebral Infarction/Ischemic Stroke

1. Accurate diagnosis is key! A CT Scan must be done to rule out a hemorrhagic stroke
before initiation of any treatment.

most patients do not have impaired consciousness in the first 24 hours

if consciousness is impaired, suspect a stroke-related seizure, hemorrhage, hypoxia or
increased intracranial pressure

2. Supportive care

Maintain adequate tissue oxygenation: May require airway support and ventilatory
assistance. Check for possible aspiration pneumonia.
BP: In most cases, BP should not be lowered. If severe HTN, lower BP cautiously as
neurological status may worsen when BP is lowered.
Volume status: Correct for hypovolemia and keep electrolytes in the normal range.
Fever: treat and look for source of fever.
Hypoglycemia/hyperglycemia: Keep under control. Hyperglycemia may worsen the
ischemic injury.
DVT Prophylaxis: This is a must as stroke patients have a high risk for DVT! It is
important to use either sc heparin 5,000 IU q. 8 or 12 hrs. or sc enoxaparin 30 mg q.
12 hrs. plus early ambulation!

3. Pharmacologic Therapy

Recombinant Tissure Plasminogen Activator (r-tPA) Protocol--(For Select Patients Only!!)

1. efficacy is influenced by the length of time between the onset of the stroke and the
initiation of treatment
2. rapid diagnosis and immediate administration of tPA increases its efficacy and may limit
the potential for hemorrhagic conversion of ischemic stroke

3. Inclusion Criteria:

ischemic stroke within 3 hours

SBP < 185; DBP < 110

4. Exclusion Criteria:

isolated neurological deficit

another stroke or serious head injury within the previous 3 months
INR > 1.7
use of heparin in the prior 48 hours
major surgery in the prior 14 days
platelet count < 100,000/mm3

5. tPA dose:

0.9 mg/kg body weight; max. dose 90 mg

give 10% of the dose as a bolus over 1-2 minutes and the rest as a continuous infusion over
1 hour
No antiplatelets or anticoagulants within 24 hours!!

6. Results:

improved outcome with regard to disability and death that persists 3 months after therapy
there is a higher incidence of intracerebral hemorrhage (6.4% vs. 0.6%)

Intra-arterial Thrombolysis

1. early clot lysis and recanalization in about 50% of the patients with intra-arterial
streptokinase and urokinase

2. intra-arterial r-pro UK 6 mg given within 6 hours of the stroke resulted in a 58%

recanalization rate vs. 14% with placebo

3. main concern is hemorrhagic transformation of the ischemic lesion

4. risk of bleeding may increase with concomitant heparin

5. should still be considered investigational until further data collected

Heparin
1. useful for progressing stroke; questionable role in stable or improving stroke

2. dosing: 50-70 U/kg as a loading dose, followed by 10-25 U/kg/hour; goal PTT 1.5-2.0X
control

3. may opt to not use a loading dose in these patients

4. major concerns are conversion of an ischemic stroke into a hemorrhagic stroke

secondary to heparin, bleeding and thrombocytopenia

5. careful selection of patients is important

Low-Molecular Weight Heparin (LMWH)

1. Org 10172 has been studied in acute stroke patients

2. synthetic low-molecular-weight fraction of heparin

3. undergoing investigation in several clinical trials

4. less risk of hemorrhage(?) and thrombocytopenia(?)

5. cannot be recommended for treatment until the results of an ongoing multicenter study
are reported

Ancrod (ARVIN)

1. derived from the venom of the Malayan pit viper snake

2. enzyme that breaks down fibrinogen to a soluble ancrod-fibrin complex without allowing
stabilization of fibrin (fibrin is not cross-linked)

3. may stimulate tPA activation from vascular endothelium

4. causes fibrinolysis soon after administration; low risk of hemorrhagic complications

5. dose: 0.5 U/kg in NS over 6 hours; administered for 7 days following stroke in the clinical
trials; titrate to a fibrinogen level of 0.5-1.0 g/L

6. cannot recommend for use until further clinical trials are completed; role in therapy not
yet established

4. Investigational Therapies for Acute Ischemic Stroke

Dextran Infusion
1. decreased blood viscosity by volume expansion

2. decreased platelet function

3. decreased blood interaction with endothelium

Prostacyclin

1. potent vasodilator and platelet suppressant

2. has fibrinolytic activity

Calcium Channel Blockers

1. may increase CBF by smooth muscle relaxation

2. may preserve neuronal function by preventing the calcium influx into neurons that
occurs during ischemia

3. nimodipine 30 mg PO every 6 hours for 28 days used in clinical trials; nicardipine also
evaluated

4. role in therapy not fully known at this time; seems to work best if initiated within 6-8
hours of symptom onset

Hemodilution

1. utilize albumin and fluids to decrease hematocrit to 30- 35% which decreases blood
viscosity

2. questionable role in therapy

21-Aminosteroids (Tirilazad Mesylate-FREEDOX)

1. during ischemia, free radicals are formed which initiate lipid peroxidation

2. 21-aminosteroids are potent inhibitors of lipid peroxidation

3. doses up to 6.0 mg/kg/day divided into 4 doses IV x 5 days have been shown to be
beneficial in clinical trials

4. role in therapy not yet defined; studies still ongoing

Mannitol (Systemic)
VA CLASSIFICATION
Primary: CV709
Secondary: OP115

Commonly used brand name(s): Osmitrol.

Note: For a listing of dosage forms and brand names by

country availability, see Dosage Forms section(s).

Category:

Diuretic—

antiglaucoma agent (systemic)—

antihemolytic—

Indications

Note: Bracketed information in the Indications section refers

to uses that are not included in U.S. product labeling.

Accepted
Acute renal failure, oliguric phase (prophylaxis and treatment)
—Mannitol, administered intravenously, is indicated to
promote diuresis in the prevention and/or treatment of the
oliguric phase of acute renal failure before irreversible renal
failure becomes established {01}.

Edema, cerebral (treatment){01} or

Intracranial pressure, elevated (treatment){01}—Mannitol,
administered intravenously, is indicated to reduce intracranial
pressure and treat cerebral edema by reducing brain
mass {01}.

Intraocular pressure, elevated (treatment){01}—Mannitol,

administered intravenously, is indicated to reduce elevated
intraocular pressure after other methods have failed or in
preparation for intraocular surgery. {01} {03} {04} {05} {06}

Toxicity, nonspecific (treatment)—Mannitol, administered

intravenously, is indicated to promote urinary excretion of and
prevent renal damage due to toxic substances (for example,
salicylates, barbiturates, bromides, lithium). {01} {03} {04} {05} {06}

Hemolysis (prophylaxis)—Mannitol, when used as an

irrigating solution, is indicated to prevent hemolysis and
hemoglobin buildup during transurethral prostatic resection or
other transurethral surgical procedures. {03} {04} {05} {06} [It has
also been used to prevent hemolysis during cardiopulmonary
bypass procedures.]1
Unaccepted
Mannitol has been used to measure glomerular filtration rate
(GFR) in acute oliguria but has generally been replaced by
more accurate tests.

1
Not included in Canadian product labeling.

Pharmacology/Pharmacokinetics

Physicochemical characteristics:
Molecular weight—
182.17 {01}

Mechanism of action/Effect:

Mannitol is an osmotic diuretic that is metabolically inert in

humans and occurs naturally, as a sugar, in fruits and
vegetables {01}.

Osmotic agent (systemic):

Mannitol elevates blood plasma osmolality, resulting in

enhanced flow of water from tissues, including the brain and
cerebrospinal fluid, into interstitial fluid and plasma. As a
result, cerebral edema, elevated intracranial pressure, and
cerebrospinal fluid volume and pressure may be reduced.

Diuretic:

Induces diuresis because mannitol is not reabsorbed in the

renal tubule, thereby increasing the osmolality of the
glomerular filtrate, facilitating excretion of water, and inhibiting
the renal tubular reabsorption of sodium, chloride, and other
solutes {01}. It may, therefore, promote the urinary excretion of
toxic materials and protect against nephrotoxicity by
preventing the concentration of toxic substances in the tubular
fluid.

Antiglaucoma agent:

Elevates blood plasma osmolarity, resulting in enhanced flow

of water from the eye into plasma and a consequent reduction
in intraocular pressure.

Antihemolytic:

When used as an irrigating solution in transurethral prostatic

resection, dilute solutions of mannitol may minimize the
hemolytic effect of water used alone. The entrance of
hemolyzed blood into the circulation and the resultant
hemoglobinemia may also be reduced.

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