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1/22/2018 Ischemic Stroke Treatment & Management: Approach Considerations, Emergency Response and Transport, Acute Management of Stroke

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Ischemic Stroke Treatment &

Updated: Jul 12, 2017
Author: Edward C Jauch, MD, MS, FAHA, FACEP; Chief Editor: Helmi L Lutsep,
MD more...


Approach Considerations
The central goal of therapy in acute ischemic stroke is to preserve tissue in the
ischemic penumbra, where perfusion is decreased but sufficient to stave off
infarction. Tissue in this area of oligemia can be preserved by restoring blood flow to
the compromised area and optimizing collateral flow.

Recanalization strategies, including the administration of intravenous (IV)

recombinant tissue-type plasminogen activator (rt-PA) and intra-arterial approaches,
attempt to establish revascularization so that cells in the penumbra can be rescued
before irreversible injury occurs. Restoring blood flow can mitigate the effects of
ischemia only if performed quickly.

Many surgical and endovascular techniques have been studied in the treatment of
acute ischemic stroke. Carotid endarterectomy has been used with some success in
the acute management of internal carotid artery occlusions, but no evidence
supports its use acutely in ischemic stroke.

In addition to limiting the duration of ischemia, an alternative strategy is to limit the

severity of ischemic injury (ie, neuronal protection). Neuroprotective strategies are
intended to preserve the penumbral tissues and to extend the time window for
revascularization techniques. At the present time, however, no neuroprotective
agents have been shown to impact clinical outcomes in ischemic stroke.

Palliative care
Palliative care is an important component of comprehensive stroke care. Some
patients with severe strokes die during the initial hospitalization, others will be
severely disabled and palliative care can begin to address the patient's and family's
short- and long-term needs. Some patients have advance directives providing
instructions for medical providers in the event of severe medical illness or injury. 1/45
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Clinical education

Prehospital care providers are essential to timely stroke care. Course curricula for
prehospital care providers are beginning to include more information on stroke than
ever before. Through certification and Acute Cardiac Life Support (ACLS)
instruction, as well as continuing medical education classes, prehospital care
providers can remain current on stroke warning signs, prehospital stroke tools, and
triage protocols in their region, and can promote stroke awareness in their own

Physician and nursing staff involved in the care of stroke patients, in the Emergency
Department (ED) and in the hospital, should participate in scheduled stroke
education. This will help them to maintain the skills required to treat stroke patients
effectively and to remain current on medical advances for all stroke types.

Emergency Response and Transport

Recognition that a stroke may have occurred, activation of 911, and rapid transport
to the appropriate receiving facility are necessary to provide stroke patients with the
best chance for acute interventions. Of patients with signs or symptoms of stroke,
29-65% utilize some facet of the emergency medical services (EMS) system. [74, 75]

Most of the patients who call EMS are those who present within 3 hours of symptom
onset. Calls to 911 and the use of EMS are associated with shorter time periods
from symptom onset to hospital arrival. [76, 77]

Stroke should be a priority dispatch with prompt EMS response. EMS responders
should perform a brief H&P, obtain time of symptom onset or last known normal,
perform a prehospital stroke assessment, determine blood glucose levels, and
provide advance notice to their ED destination in as timely a manner as possible so
as to allow preparation and marshalling of personnel and resources. With the
development of stroke center designation, which is currently in progress, such
centers would then become the preferred destination for patients with acute stroke
symptoms who utilize EMS.

Data supporting the use of emergency air transport for patients with acute stroke
symptoms are limited. Further evaluation of this transportation modality is necessary
to minimize the potentially high number of stroke mimics and to maximize the
appropriate use of transport resources. Telemedicine is also a technology that can
provide timely expert advice to rural and underserved clinics and hospitals. [1]

Acute Management of Stroke

The goal for the emergent management of stroke is to assess the patient’s airway,
breathing, and circulation (ABCs); stabilize the patient as necessary; and complete
initial evaluation and assessment, including imaging and laboratory studies, within
60 minutes of patient arrival. [1] A Finnish study demonstrated that time to treatment 2/45
1/22/2018 Ischemic Stroke Treatment & Management: Approach Considerations, Emergency Response and Transport, Acute Management of Stroke

with fibrinolytics can be decreased with changes in EMS and ED coordination and in
ED procedures for treating acute stroke patients. [78]

A US study in which a multidisciplinary team used value stream analysis to assess

the steps required to treat acute ischemic stroke with IV rt-PA found several
inefficiencies in the protocol (eg, in patient routing) that were slowing treatment. Use
of a revised protocol that targeted those inefficiencies reduced door-to-needle times
from 60 to 39 minutes and increased the percentage of patients treated in 60
minutes or less after hospital arrival from 52% to 78%, with no change in
symptomatic hemorrhage rate. [79]

Critical decisions focus on the need for airway management, establishment of

optimal blood pressure control, and identification of potential reperfusion therapies
(IV fibrinolysis with rt-PA or intra-arterial approaches). Involvement of a physician
with stroke expertise is ideal. Stroke care units with specially trained personnel exist
and improve outcomes.

Comorbid medical conditions also need to be addressed. Hyperthermia is
infrequently associated with stroke but can increase morbidity. Administration of
acetaminophen, by mouth or per rectum, is indicated in the presence of fever
(temperature >100.4°F).

Oxygen supplementation

Supplemental oxygen is recommended when the patient has a documented oxygen

requirement (ie, oxygen saturation < 95%). In the small proportion of patients with
stroke who are relatively hypotensive, administration of IV fluid, vasopressor
therapy, or both may improve flow through critical stenoses.

Hypoglycemia and hyperglycemia

Hypoglycemia needs to be identified and treated early in the evaluation. In contrast,
the management of hyperglycemia in acute stroke remains an area of uncertainty.
[80] Extreme hyperglycemia is detrimental in the setting of acute stroke.

Hyperglycemia is common after acute ischemic stroke, even in patients without

diabetes. A Cochrane review found that the use of IV insulin to maintain serum
glucose in the range of 4-7.5 mmol/L (72-135 mg/dL) in the first 24 hours of
ischemic stroke did not improve functional outcome, death rates, or final neurologic
deficit and significantly increased the risk of hypoglycemia. [81]

Fibrinolytic Therapy
The only fibrinolytic agent that has been shown to benefit selected patients with
acute ischemic stroke is alteplase (rt-PA). While streptokinase may benefit patients 3/45
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with acute MI, in patients with acute ischemic stroke it has been shown to increase
the risk of intracranial hemorrhage and death.

Fibrinolytics (ie, rt-PA) restore cerebral blood flow in some patients with acute
ischemic stroke and may lead to improvement or resolution of neurologic deficits.
Unfortunately, fibrinolytics may also cause symptomatic intracranial hemorrhage.
Other complications include potentially extracranial hemorrhage and angioedema or
allergic reactions. [1]

Inclusion/exclusion criteria
Therefore, if the patient is a candidate for fibrinolytic therapy, a thorough review of
the inclusion and exclusion criteria must be performed. The exclusion criteria largely
focus on identifying risk of hemorrhagic complications associated with fibrinolytic
use. The American Heart Association/American Stroke Association (AHA/ASA)
inclusion guidelines for the administration of rt-PA are as follows [1] :

Diagnosis of ischemic stroke causing measurable neurologic deficit

Neurologic signs not clearing spontaneously to baseline
Neurologic signs not minor and isolated
Symptoms not suggestive of subarachnoid hemorrhage
No head trauma or prior stroke in past 3 months
No myocardial infarction (MI) in past 3 months
No gastrointestinal/genitourinary hemorrhage in previous 21 days
No arterial puncture in a noncompressible site during the past 7 days
No major surgery in past 14 days
No history of prior intracranial bleeding
Systolic blood pressure under 185 mm Hg, diastolic blood pressure under 110
mm Hg
No evidence of acute trauma or bleeding
Not taking an oral anticoagulant, or if so, international normalized ratio (INR)
under 1.7
If taking heparin within 48 hours, a normal activated prothrombin time (aPT)
Platelet count of more than 100,000/μL
Blood glucose greater than 50 mg/dL (2.7 mmol)
CT scan does not show evidence of multilobar infarction (hypodensity over
one third hemisphere) or intracerebral hemorrhage
The patient and family understand the potential risks and benefits of therapy

Whereas these inclusion/exclusion criteria are from the original FDA approval, a
more recent revision by the FDA of the product insert has reclassified many prevous
absolute contraindications to now relative contraindications. Furthermore,
subsequent data and experience have allowed some patients with what were
previously considered relative contraindications to be safely treated. Involvement of
a physician with stroke expertise is critical for assessing the risk/benefit
consideration for these groups of patients.

Time to therapy 4/45
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An rt-PA stroke study group from the National Institute of Neurologic Disorders and
Stroke (NINDS) first reported that the early administration of rt-PA benefited
carefully selected patients with acute ischemic stroke. [3] The FDA subsequently
approved the use of rt-PA in patients who met NINDS criteria. In particular, rt-PA had
to be given within 3 hours of stroke onset and only after CT scanning had ruled out
hemorrhagic stroke.

Subsequently, fibrinolytic therapy administered 3-4.5 hours after symptom onset

was found to improve neurologic outcomes in the European Cooperative Acute
Stroke Study III (ECASS III), suggesting a wider time window for fibrinolysis in
carefully selected patients. [82] On the basis of these and other data, in May 2009
the AHA/ASA revised the guidelines for the administration of rt-PA after acute
stroke, expanding the window of treatment from 3 hours to 4.5 hours to provide
more patients with an opportunity to benefit from this therapy. [82, 83, 84, 85]

Eligibility criteria for treatment during this later period are similar to those for earlier
treatment but are more stringent, with any 1 of the following serving as an additional
exclusion criterion:

Age older than 80 years

Use of oral anticoagulants, regardless of the INR
Baseline score on the National Institutes of Health Stroke Scale (NIHSS)
greater than 25
History of stroke and diabetes

In a meta-analysis of nine major trials of fibrinolysis treatment involving a total of

6756 patients with acute ischemic stroke, researchers found that administration of
alteplase within 4.5 hours of stroke onset significantly improved outcomes,
irrespective of age or stroke severity, with earlier treatment providing the greatest
benefit. Good outcome was defined as modified Rankin score of 0 or 1, which
indicates little or no residual disability at 3-6 months. The odds of a good stroke
outcome were 75% higher for patients who received alteplase within 3 hours of
symptom onset compared with those who did not. Patients given alteplase 3 to 4.5
hours after symptom onset had a 26% increased chance of a good outcome, and
patients with a delay of more than 4.5 hours in receiving alteplase treatment had a
nonsignificant 15% increase in the chance of a good recovery. [86, 87]

A 10-center European study of nearly 6900 patients found IV rt-PA to be most

effective when given within 90 minutes of the onset of stroke symptoms. [88, 89]
Patients scoring in the 7-12 range on the NIHSS had better outcomes when
fibrinolytic therapy was provided within 90 minutes of symptom onset than when it
was provided 90-270 minutes after onset. For patients with minor stroke or
moderate-to-severe stroke, however, treatment within the initial 90-minute window
provided no additional advantage.

Hemorrhage risk 5/45
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Although antiplatelet therapy may increase the risk for symptomatic intracerebral
hemorrhage with fibrinolysis, a study by Diedler et al that included 3782 patients
who had received 1 or 2 antiplatelet drugs found that the risk of intracerebral
hemorrhage was small compared with the documented benefit of fibrinolysis. [90]
These researchers concluded that antiplatelet treatment should not be considered a
contraindication to fibrinolysis, although caution is warranted in patients receiving
the combination of aspirin and clopidogrel.

A 2015 study, the largest of its kind, provides data supporting the use of fibrinolysis
for stroke in patients taking antiplatelet therapy. Researchers analyzed a cohort of
more than 85,000 stroke patients who had received tPA, approximately half of whom
were taking antiplatelet medication at the time of their stroke. Results show that
among patients with an acute ischemic stroke treated with intravenous tPA, those
receiving antiplatelet therapy before the stroke had a higher risk for hemorrhage but
better functional outcomes than those who were not receiving antiplatelet therapy.

Data regarding the safety of fibrinolytic therapy in patients taking dabigatran,

rivaroxaban, or apixaban are not available. Extreme caution should be used when
considering fibrinolytic therapy in such patients.

Caution should also be exercised in the administration of rt-PA to patients with

evidence of low attenuation (edema or ischemia) involving more than a third of the
distribution of the middle cerebral artery (MCA) on their initial noncontrast CT scan;
such patients are less likely to have a favorable outcome after fibrinolytic therapy
and are at higher risk for hemorrhagic transformation of their ischemic stroke. [51]

Ultrasound therapy
Researchers have studied the use of transcranial ultrasound as a means of
assisting rt-PA in fibrinolysis. [92, 93] By delivering mechanical pressure waves to the
thrombus, ultrasound can theoretically expose more of the thrombus’s surface to the
circulating fibrinolytic agent. Further research is necessary to determine the exact
role of transcranial Doppler ultrasound in assisting fibrinolytics in acute ischemic

For more information, see Thrombolytic Therapy in Stroke and Reperfusion Injury in

Intra-arterial Reperfusion
Theoretically, intra-arterial delivery may produce higher local concentrations of the
fibrinolytic agent at lower total doses (and thus possibly lower the risk of a systemic
bleed) and allow a longer therapeutic window. However, the longer time for initiating
intra-arterial administration may mitigate some of this advantage and earlier phase II
studies did not show a statistically significant difference in clinical outcomes. [1] 6/45
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The Interventional Management of Acute Stroke Study (IMS-III) was halted for futility
after showing no additional benefit from intra-arterial therapies (rt-PA, mechanical
thrombectomy with mostly first-generation devices, or both) compared with
intravenous rt-PA in patients with large-vessel occlusions. Additional analyses of the
IMS III data are under way to better understand the results and potentially identity
subsets of patients who may benefit from the combined approach. [94]

Intra-arterial fibrinolysis has been the traditional approach for patients with stroke
from basilar artery occlusion. However, results of the Basilar Artery International
Cooperation Study (BASICS), a prospective registry study in 592 patients, did not
support unequivocal superiority of intra-arterial fibrinolysis over intravenous
fibrinolysis. [95]

A meta-analysis of case studies involving a total of 420 patients with basilar artery
occlusion did indicate that recanalization was achieved more frequently with intra-
arterial fibrinolysis than with intravenous fibrinolysis (65% vs 53%), but the report
also found that death and long-term disability were equally common with the 2
techniques. [96] These researchers concluded that intravenous fibrinolysis
represents probably the best treatment that can be offered to these patients in
hospitals without a 24-hour interventional neuroradiologic service. [96]

Antiplatelet Agents
AHA/ASA guidelines recommend giving aspirin, 325 mg orally, within 24-48 hours of
ischemic stroke onset. The benefit of aspirin is modest but statistically significant
and appears principally to involve the reduction of recurrent stroke. [85]

The International Stroke Trial and the Chinese Acute Stroke Trial (CAST)
demonstrated modest benefit from the use of aspirin in the setting of acute ischemic
stroke. The International Stroke Trial randomized 19,435 patients within 48 hours of
stroke onset to treatment with aspirin 325 mg, subcutaneous heparin in 2 different
dose regimens, aspirin with heparin, and a placebo. The study found that aspirin
therapy reduced the risk of stroke recurrence within 14 days (2.8% vs 3.9%), with no
significant excess of hemorrhagic strokes. [97, 98]

In CAST, which included 21,106 patients, aspirin treatment (160 mg/day) that was
started within 48 hours of the onset of suspected acute ischemic stroke and was
continued in hospital for up to 4 weeks reduced mortality to 3.3%, compared with
3.9% with placebo. A separate study also found that the combination of aspirin and
low–molecular-weight heparin did not significantly improve outcomes. [97]

Other antiplatelet agents have also been under evaluation for use in the acute
presentation of ischemic stroke. In a preliminary pilot study, abciximab given within 6
hours showed a trend toward improved outcome at 3 months. [99] However, the
phase 3 Abciximab in Emergency Treatment of Stroke Trial (AbESTT-II) was
terminated prematurely after 808 patients because of lack of efficacy and an 7/45
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increased rate of symptomatic or fatal intracranial hemorrhage in patients receiving

abciximab. [100]

Blood Pressure Control

Although hypertension is common in acute ischemic stroke and is associated with
poor outcome, studies of antihypertensive treatment in this setting have produced
conflicting results. A theoretical drawback of blood pressure reduction is that
elevated blood pressure may counteract dysfunctional cerebral autoregulation from
stroke, but limited evidence suggests that antihypertensive treatment in acute stroke
does not change cerebral perfusion. [101]

Calcium channel blockers did not alter outcome after ischemic stroke in some trials.
Possible adverse effects of antihypertensive treatment have been reported in certain
trials, especially those using intravenous calcium channel blockers or oral beta
blockers. In the Controlling Hypertension and Hypotension Immediately Post-Stroke
(CHHIPS) trial, early lowering of blood pressure with labetalol and lisinopril slightly
improved outcome and did not increase serious adverse events. However, CHHIPS
had a small sample size. [102]

A study in 339 patients with ischemic stroke found that oral candesartan reduced
combined vascular events but had no effect on disability. [101] However, the
Scandinavian Candesartan Acute Stroke Trial (SCAST), a randomized, placebo-
controlled, double-blind study involving 2029 patients, found no indication of benefit
from candesartan but did find some suggestion of harm. [103]

In the single-blind, randomized China Antihypertensive Trial in Acute Ischemic

Stroke (CATIS) study, which included 4,071 patients with acute ischemic stroke and
elevated blood pressure, immediate blood pressure reduction with antihypertensive
medication within 48 hours of symptom onset did not reduce the risk for death or
major disability. CATIS excluded patients who received fibrinolytic therapy. Mean
systolic blood pressure was reduced from 166.7 to 144.7 mm Hg within 24 hours in
the antihypertensive treatment group. [104, 105]

Among the 2,038 patients who received antihypertensive treatment, 683 reached
the primary endpoint of death or major disability at 14 days or hospital discharge,
compared with 681 of the 2,033 patients who received no antihypertensive
treatment. At 3-month follow-up, 500 patients in the antihypertensive treatment
group and 502 patients in the control group reached the secondary endpoint of
death or major disability. [104, 105]

For patients who are not candidates for fibrinolytic therapy, current guidelines
recommend permitting moderate hypertension in most patients with acute ischemic
stroke. Most patients will experience spontaneous reduction in blood pressure over
the first 24 hours without treatment. [85] The exceptions would be patients who have
active comorbidities (eg, aortic dissection, acute myocardial infarction [MI], 8/45
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decompensated heart failure, hypertensive emergency) that require emergent blood

pressure management.

Thresholds for antihypertensive treatment in acute ischemic stroke patients who are
not fibrinolysis candidates, according to the 2013 ASA guidelines, are systolic blood
pressure higher than 220 mm Hg or diastolic blood pressure above 120 mm Hg. [85]
In those patients, a reasonable goal is to lower blood pressure by 15% during the
first 24 hours after onset of stroke. Care must be taken to not lower blood pressure
too quickly or aggressively, since this could worsen perfusion in the penumbra.

Mechanical Thrombectomy
Mechanical clot disruption is an alternative for patients in whom fibrinolysis is
ineffective or contraindicated.

In 2015, The American Heart Association/American Stroke Association issued

updated guidelines for the emergency treatment of patients with acute ischemic
stroke, recommending endovascular treatment using the newer generation stent
retrievers. [106] Currently, 4 devices are approved by the FDA for the endovascular
treatment of acute ischemic stroke, as follows:

Merci Retriever (Concentric Medical, Mountain View, CA): Corkscrew-shaped

device that captures and engages clots
Penumbra System (Penumbra, Alameda, CA): Employs both aspiration and
Solitaire FR Revascularization Device (Covidien, Dublin, Ireland): Stent-
retriever system; combines the ability to restore blood flow and retrieve clot
Trevo (Concentric Medical, Mountain View, CA): Stent-retriever system

Successful recanalization occurred in 12 of 28 patients in the Mechanical Embolus

Retrieval in Cerebral Ischemia (MERCI) 1 pilot trial, a study of the Merci Retrieval
System. [107] In a second MERCI study, recanalization was achieved in 48% of
patients in whom the device was deployed. Clot was successfully retrieved from all
major cerebral arteries; however, the recanalization rate for the MCA was lowest.

The Multi MERCI trial used the newer-generation Concentric retrieval device (L5).
Recanalization was demonstrated in approximately 55% of patients who did not
receive t-PA and in 68% of those to whom t-PA was given. Seventy-three percent of
patients who failed intravenous t-PA therapy had recanalization following
mechanical embolectomy. [109] On the basis of these results, the FDA cleared the
use of the MERCI device in patients who are either ineligible for or who have failed
intravenous fibrinolytics.

In a trial of the Penumbra System in 23 patients who presented within 8 hours of

symptom onset, revascularization to a Thrombolysis in Myocardial Infarction (TIMI)
grade of 2 or 3 was accomplished in all 21 treated vessels. Vessel tortuosity
prevented access by the device in 3 patients. [110] 9/45
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More recent trials of the stent-retriever systems demonstrated superiority in

reperfusion over the original Merci systems. In the Solitaire Flow Restoration Device
Versus the Merci Retriever in Patients with Acute Ischaemic Stroke (SWIFT) study,
which enrolled 113 subjects with moderate or severe strokes within 8 hours after
symptom onset, the Solitaire FR system demonstrated successful revascularization
(TIMI 2-3 flow) in 61% of patients, compared with 24% of patients treated with the
Merci system. Patients in the Solitaire FR group also had a higher rate of good 90-
day clinical outcomes than did those in the Merci group (58% versus 33%,
respectively). [111]

A similar study, the Trevo Versus Merci Retrievers for Thrombectomy

Revascularisation of Large Vessel Occlusions in Acute Ischaemic Stroke (TREVO 2)
trial, reported successful reperfusion (TIMI 2-3 flow) in 86% of patients using the
Trevor stent retriever, compared with 60% in the Merci group. The rate of good
clinical outcomes at 90 days was also higher in the Trevo group than in the Merci
group (40% vs 22%, respectively). [112] Ongoing studies will better define the role of
intra-arterial therapies with and without intravenous fibrinolysis.

For more information, see Mechanical Thrombolysis in Acute Stroke.

Fever Control
Antipyretics are indicated for febrile stroke patients, since hyperthermia accelerates
ischemic neuronal injury. Substantial experimental evidence suggests that mild brain
hypothermia is neuroprotective. The use of induced hypothermia is currently being
evaluated in phase II clinical trials. [113, 114, 115]

High body temperature in the first 12-24 hours after stroke onset has been
associated with poor functional outcome. However, results from the Paracetamol
(Acetaminophen) in Stroke (PAIS) trial did not support the routine use of high-dose
acetaminophen (6 g daily) in patients with acute stroke, although post-hoc analysis
suggested a possible beneficial effect on functional outcome in patients admitted
with a body temperature of 37-39° C. [116]

Cerebral Edema Control

Significant cerebral edema after ischemic stroke is thought to be somewhat rare
(10-20%). Maximum severity of edema is typically reached 72-96 hours after the
onset of stroke.

Early indicators of ischemia on presentation and on noncontrast CT (NCCT) scans

are independent indicators of potential swelling and deterioration (see the image
below). Mannitol and other therapies to reduce intracranial pressure (ICP) may be
used in emergency situations, although their usefulness in swelling secondary to
ischemic stroke is unknown. No evidence exists supporting the use of
corticosteroids to decrease cerebral edema in acute ischemic stroke. Prompt
neurosurgical assistance should be sought when indicated. [1] 10/45
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Axial noncontrast computed tomography (NCCT) scan demonstrates diffuse hypodensity in

the right lentiform nucleus with mass effect upon the frontal horn of the right lateral ventricle in
a 70-year-old woman with a history of left-sided weakness for several hours.
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Patient position, hyperventilation, hyperosmolar therapy, and, rarely, barbiturate

coma may be used, as in patients with increased ICP secondary to closed head
injury. Hemicraniectomy has been shown to decrease mortality and disability among
patients with large hemispheric infarctions associated with life-threatening edema.
[117, 118, 119, 120]

The American Heart Association and the American Stroke Association have
released a guideline for the management of cerebral and cerebellar infarction with
brain swelling; recommendations include the following [121, 122] :

Selected patients, including those able to handle an aggressive rehabilitation

program, may benefit from decompressive craniectomy; younger patients may
benefit most, and surgery is not recommended for patients older than 60 years
Clinical evidence of deterioration in swollen supratentorial hemispheric
ischemic stroke includes new or further impairment of consciousness, cerebral
ptosis, and changes in pupillary size
In patients with swollen cerebellar infarction, level of consciousness decreases
because of brainstem compression; this decrease may include early loss of
corneal reflexes and the development of miosis
Standardized definitions are needed to facilitate studies of incidence,
prevalence, risk factors, and outcomes
Identification of high-risk patients should include both clinical and
neuroimaging data 11/45
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Complex medical care of these patients includes airway management and

mechanical ventilation, blood pressure control, fluid management, and glucose
and temperature control
In patients with swollen supratentorial hemispheric ischemic stroke, routine
intracranial pressure monitoring or cerebrospinal fluid diversion is not
indicated, but in patients who continue to deteriorate neurologically,
decompressive craniectomy with dural expansion should be considered
In patients with swollen cerebellar stroke who deteriorate neurologically,
suboccipital craniectomy with dural expansion should be performed
After a cerebellar infarct, performance of ventriculostomy to relieve obstructive
hydrocephalus should be accompanied by decompressive suboccipital
craniectomy to avoid deterioration from upward cerebellar displacement
As many as one third of patients with swollen hemispheric supratentorial
infarcts will be severely disabled and fully dependent on care even after
decompressive craniectomy, whereas most patients with cerebellar infarct will
have acceptable functional outcomes after surgery

Seizure Control
Seizures occur in 2-23% of patients within the first days after ischemic stroke. These
seizures are usually focal, but they may be generalized. Although primary
prophylaxis for poststroke seizures is not indicated, secondary prevention of
subsequent seizures with standard antiepileptic therapy is recommended. [1]

A fraction of patients who have experienced stroke develop chronic seizure

disorders. Seizure disorders secondary to ischemic stroke should be managed in
the same manner as other seizure disorders that arise as a result of neurologic
injury. [1]

Acute Decompensation
In the case of the rapidly decompensating patient or the patient with deteriorating
neurologic status, reassessment of the ABCs as well as hemodynamics and
reimaging are indicated. Many patients who develop hemorrhagic transformation or
progressive cerebral edema will demonstrate acute clinical decline. Rarely, a patient
may have escalation of symptoms secondary to increased size of the ischemic
penumbra. Careful observation for hemorrhagic transformation (especially in the first
24 hours postreperfusion) and cerebral edema in patients with hemispheric or
posterior fossa strokes in the first 24-36 hours is warranted.

Anticoagulation and Prophylaxis

Currently, data are inadequate to justify the routine use of heparin or other
anticoagulants in the acute management of ischemic stroke. [123] Patients with
embolic stroke who have another indication for anticoagulation (eg, atrial fibrillation)
may be placed on anticoagulation therapy nonemergently, with the goal of 12/45
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preventing further embolic disease; however, the potential benefits of that

intervention must be weighed against the risk of hemorrhagic transformation. [1] For
more information, see Stroke Anticoagulation and Prophylaxis.

Immobilized stroke patients in particular are at increased risk of developing deep

venous thrombosis (DVT) and should receive early efforts to reduce the occurrence
of DVT. The use of low-dose, subcutaneous unfractionated or low–molecular-weight
heparin may be appropriate in these cases. [1] The CLOTS (Clots in Legs Or
sTockings after Stroke) trial demonstrated that intermittent pneumatic compression
of the lower extremities, started in the first 3 hospital days, reduced the risk of DVT
in immobile patients with acute stroke. [124]

Neuroprotective Agents
The rationale for the use of neuroprotective agents is that reducing the release of
excitatory neurotransmitters by neurons in the ischemic penumbra may enhance the
survival or these neurons. Despite very promising results in several animal studies,
however, no single neuroprotective agent in ischemic stroke has as yet been
supported by randomized, placebo-controlled human studies. Nevertheless,
substantial research is under way evaluating different neuroprotective strategies.

Hypothermia was very promising for the ongoing treatment of patients surviving
cardiac arrest from ventricular tachycardia or ventricular fibrillation. However, no
major clinical study has demonstrated a role for hypothermia in the early treatment
of ischemic stroke. [1]

For more information, see Neuroprotective Agents in Stroke.

Stroke Prevention
Primary prevention refers to the management of individuals with no history of stroke.
Preventative measures may include the use of antiplatelet agents, statins, smoking
cessation and exercise. The 2011 AHA/ASA guidelines for the primary prevention of
stroke emphasize the importance of lifestyle changes to reduce well-documented
modifiable risk factors, citing an 80% lower risk of a first stroke in people who follow
a healthy lifestyle compared with those who do not. [22]

Secondary prevention refers to the treatment of individuals who have already had a
stroke. Measures may include the use of anitplatelet agents, [125] anticoagulants
(warfarin or newer novel oral anticoagulants) antihypertensives, statins, [126] and
lifestyle interventions. A study by the Warfarin-Aspirin Symptomatic Intracranial
Disease Trial Investigators concluded that in stroke patients who have significant
intracranial arterial stenosis, aspirin should be used in preference to warfarin for
secondary prevention. [127]

Smoking cessation, blood pressure control, diabetes control, a low-fat low-salt diet,
weight loss, and regular exercise should be encouraged as strongly as the 13/45
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medications described above. The 2011 AHA/ASA guidelines recommend ED-

based smoking cessation interventions, and consider it reasonable for EDs to
screen patients for hypertension and drug abuse. [22]

Written prescriptions for exercise and medications for smoking cessation (ie,
nicotine patch, bupropion, varenicline) increase the likelihood of success with these
interventions. In addition, the 2011 AHA/ASA guidelines for primary stroke
prevention indicate that it is reasonable to avoid exposure to environmental tobacco
smoke, despite a lack of stroke-specific data.

Aspirin for primary prevention

Overall, the value of aspirin in primary prevention appears uncertain, [128] and its
use for this purpose is not recommended for patients at low risk. Aspirin is
recommended for primary prevention only in persons with at least a 6-10% risk of
cardiovascular events over 10 years. [22]

On the other hand, low-dose aspirin may be beneficial for primary prevention of
stroke in women. A randomized, placebo-controlled trial in 39,876 initially healthy
women aged 45 years or older demonstrated that 100 mg of aspirin on alternate
days resulted in a 24% reduction in the risk of ischemic stroke, with a nonsignificant
increase in the risk of hemorrhagic stroke. [129]

Secondary prevention guidelines

Guidelines issued in 2014 by the American Heart Association (AHA)/American

Stroke Association (ASA) on the secondary prevention of stroke emphasize nutrition
and lifestyle and include a new section on aortic atherosclerosis. New
recommendations include the following [130, 131] :

Patients who have had a stroke or transient ischemic attack (TIA) should be
screened for diabetes and obesity
Patients should possibly be screened for sleep apnea
Patients should possibly undergo a nutritional assessment and be advised to
follow a Mediterranean-type diet
Patients who have had a stroke of unknown cause should undergo long-term
monitoring for atrial fibrillation (AF)
The new oral anticoagulants dabigatran (class I, level of evidence [LOE] A),
apixaban (class I, LOE B), and rivaroxaban (class IIa, LOE B) are among the
drugs recommended for patients with nonvalvular AF

Based on research results, the guidelines also recommend that, in patients without
deep venous thrombosis (DVT), a patent foramen ovale not be closed. In addition,
because there is little data to suggest that niacin or fibrate drugs, as a means to
raise high-density lipoprotein (HDL) cholesterol, reduce secondary stroke risk, the
guidelines no longer recommend their use.

Dual antiplatelet therapy for secondary prevention 14/45
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A systematic review and meta-analysis of 12 randomized trials involving 3766

patients concluded that, compared with aspirin alone, dual antiplatelet therapy with
aspirin plus either dipyridamole or clopidogrel appears to be safe and effective in
reducing stroke recurrence and other vascular events (ie, transient ischemic attack
[TIA], acute coronary syndrome, MI), in patients with acute ischemic stroke or TIA.
[132] Dual therapy was also associated with a nonsignificant trend toward increased
major bleeding.

The European/Australasian Stroke Prevention in Reversible Ischemia Trial

(ESPRIT) showed that the combination of aspirin and dipyridamole was preferable
to aspirin alone as antithrombotic therapy for cerebral ischemia of arterial origin. [133]
In ESPRIT, secondary prevention was started within 6 months of a TIA or minor
stroke of presumed arterial origin.

The addition of extended-release dipyridamole to aspirin therapy appears to be

equally safe and effective whether started early or late after stroke. A German study
in 543 patients found no significant difference in disability at 90 days, regardless of
whether dipyridamole was started within 24 hours of stroke or TIA onset or after 7
days of aspirin monotherapy. [134]

In contrast, the Management of AtheroThrombosis with Clopidogrel in High-risk

patients with recent transient ischaemic attack or ischaemic stroke (MATCH) trial,
which included 7599 patients, found that adding aspirin to clopidogrel did not
significantly reduce major vascular events. However, the risk of life-threatening or
major bleeding was increased by the addition of aspirin. [135]

Carotid artery stenosis

For patients at risk for stroke from asymptomatic carotid artery stenosis, the 2011
AHA/ASA primary prevention guidelines state that older studies that showed
revascularization surgery as more beneficial than medical treatment may now be
obsolete because of improvements in medical therapies. Therefore, individual
patient comorbidities, life expectancy, and preferences should determine whether
medical treatment alone or carotid revascularization is selected. [22]

Atrial fibrillation

Atrial fibrillation (AF) is a major risk factor for stroke. The 2011 AHA/ASA primary
stroke prevention guideline recommends that EDs screen for AF and assess
patients for anticoagulation therapy if AF is found. [22]

In the Atrial fibrillation Clopidogrel Trial with Irbesartan for prevention of Vascular
Events (ACTIVE W), oral anticoagulation with warfarin proved superior to
clopidogrel plus aspirin for prevention of vascular events in patients with AF who
were at high risk of stroke. [136] The study was stopped early because of clear
evidence of superiority of oral anticoagulation therapy. 15/45
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Interestingly, in ACTIVE W, the rate of vascular events was significantly higher in

patients who switched from warfarin to clopidogrel plus aspirin as a result of
randomization than in patients who had been on warfarin before study enrollment
and remained on warfarin during the study. The benefit of anticoagulation therapy
over dual antiplatelet therapy was much more modest in patients who had not been
on warfarin before study initiation and were then randomized to warfarin.

The 2011 ACC Foundation (ACCF)/AHA/Heart Rhythm Society (HRS) AF guideline

update states that the new anticoagulant dabigatran is useful as an alternative to
warfarin in patients with AF who do not have a prosthetic heart valve or
hemodynamically significant valve disease. [137] However, a 2012 meta-analysis
found an increased risk for MI or acute coronary syndrome with dabigatran. [138]
With the advent of other novel anticoagulants, the American Academy of Neurology
(AAN) produced guidelines for the prevention of stroke in nonvalvuar atrial fibrillation
in 2014. [139] The guidelines recommend that clinicians should administer
dabigatran, rivaroxaban, or apixaban to patients who have nonvalvular atrial
fibrillation requiring anticoagulant medication and are at higher risk of intracranial
bleeding; they also suggest that clinicians might offer apixaban to patients
with nonvalvular atrial fibrillation and GI bleeding risk who require anticoagulant
medication. The AAN guidelines recommend that where oral anticoagulants are
unavailable, clinicians might offer a combination of aspirin and clopidogrel. This
combination was found to be more effective than aspirin for reducting strokes in
atrial fibrillation in the ACTIVE trial although it did increase major hemorrhage risk.

Specialized Stroke Centers

The concept of the specialized stroke center has evolved in response to the
multitude of factors involved in the care of patients with acute stroke. The American
Heart Association and the Brain Attack Coalition provided recommendations for the
establishment of 3 tiers of stroke centers: acute stroke ready hospitals
(ASRHs), primary stroke centers (PSCs), and comprehensive stroke centers
(CSCs). [1] The Joint Commission for the Accreditation of Hospital Organizations
(JC) and others now provide accreditation for ASRH, PSCs and CSCs. These
centers are characterized as follows:

ASRH: Designed to address the lack of hospitals typically in rural areas that
have the resources to achieve PSC or CSC certification and yet serve as a
critical access point for healthcare. Typically they have all the elements of a
PSC but lack a physician with stroke expertise and often a dedicated stroke
unit. Through the use of telemedicine and teleradiology these centers can
evaluate patients for the potential use of fibrinloytics. Key to the optimal
function of these stroke centers is their interactions within a regional stroke
system of care.
PSC: Designed to maximize the timely provision of stroke-specific therapy,
including the administration of rt-PA; the center is also capable of providing
care to patients with uncomplicated stroke 16/45
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CSC: Shares the commitment that the PSC has to acute delivery of rt-PA and
also provides care to patients with hemorrhagic stroke and intracranial
hemorrhage, as well as to all patients with stroke who require emergent
advanced imaging, intra-arterial therapies, neurosurgical interventions, and
management in a neurosurgical intensive care unit (NSICU)

ASRHs, PSCs, and CSCs work most effectively when integrated into a regional
stroke system of care so that patients are treated at the most appropriate hospital
based on factors such as severity, comorbidities, and timing. Integrating regional
prehospital services (911 and EMS) into this system of care ensures the most
appropriate triage from the field.

Coordination of care
Once patients have been identified as potential stroke patients, their ED evaluation
must be fast-tracked to allow for the completion of required laboratory tests and
requisite noncontrast head CT scanning, as well as for the notification and
involvement of neurologic consultants. These requirements have led to the
development of "code stroke" protocols for the ED. In addition, EMS personnel are
trained to identify possible stroke patients and arrange for their speedy, preferential
transport to a PSC or CSC. [79]

Hospitals with specialized stroke teams have demonstrated significantly increased

rates of fibrinolytic administration, decreased door-to-needle (DTN) times, and
decreased mortality. Cumulatively, the center should identify performance measures
and include mechanisms for evaluating the effectiveness of the system, as well as
its component parts. The acute care of the stroke patient is more than anything a
systems-based team approach requiring the cooperation of the ED, radiology,
pharmacy, neurology, and intensive care unit (ICU) staff.

A stroke system should ensure effective interaction and collaboration among the
agencies, services, and people involved in providing prevention and the timely
identification, triage to the most appropriate hospital, rapid transport, treatment, and
rehabilitation of stroke patients. For more information, see Stroke Team Creation
and Primary Stroke Center Certification.

A stroke team or an experienced professional who is sufficiently familiar with stroke
should be available within 15 minutes of the patient's arrival in the ED. Other
consultations are tailored to individual patient needs. Often, occupational therapy,
physical therapy, speech therapy, and physical medicine and rehabilitation experts
are consulted within the first day of hospitalization.

Consultation of cardiology, vascular surgery, or neurosurgery may be warranted

based on the results of carotid duplex scanning , neuroimaging, transthoracic and
transesophageal echocardiography, and clinical course. During hospitalization,
additional useful consultations include the following: 17/45
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Home health care coordinator

Rehabilitation coordinator
Social worker
Psychiatrist (commonly for depression)



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Intervention Council, and the Atherosclerotic Peripheral Vascular Disease and
Quality of Care Outcomes in Research Interdisciplinary Working Groups: the
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