Cutting Edge Acute Ischemic

S t ro k e M a n a g e m e n t
a, b
Alfredo E. Urdaneta, MD *, Paulomi Bhalla, MD

KEYWORDS
 Endovascular mechanical thrombectomy  Acute ischemic stroke
 Stroke management  Stroke window  Stroke imaging  System improvement
 Process improvement

KEY POINTS
 Tissue plasminogen activator (tPA) for ischemic stroke within 4.5 hours of symptom onset
is broadly accepted and should not be withheld for those on antiplatelet agents or older
than 80 years old.
 Endovascular therapy should be considered for any patient with stroke symptoms within
24 hours of symptom onset by utilizing clinical suspicion for large vessel occlusion and
advanced neuroimaging.
 Medical management of stroke is not limited to the decision to administer tPA or endovas-
cular treatments but includes blood pressure, glucose, temperature, and oxygen
management.
 Efficient organized workflows in all stages of acute care from the prehospital setting to the
interventional radiology suite and critical care unit are necessary to optimize patient
outcomes.

INTRODUCTION

Acute ischemic stroke (AIS) is a significant medical event affecting 79,5000 people
each year,1 with substantial implications for the affected patients, their families, and
society. Rapid recognition of stroke symptoms by the emergency medicine (EM)
physician is key, because time-dependent treatments can drastically alter the neuro-
logic sequalae of an AIS. The saying, “time is brain,” should be on every EM physi-
cian’s mind when evaluating and treating a patient with possible AIS.
Many articles and guidelines for the evaluation and treatment of AIS have been previ-
ously published.2–7 Key parts of the work-up include a National Institutes of Health Stroke

Disclosure Statement: No disclosures to report.

a
Department of Emergency Medicine, Stanford University, 900 Welch Road, Suite 350, Palo
Alto, CA 94305, USA; b Department of Neurology, Stanford Health Care - Valley Care, Stanford
University, 300 Pasteur Drive, Palo Alto, CA 94304, USA
* Corresponding author.
E-mail address: [email protected]

Emerg Med Clin N Am - (2019) -–-

https://doi.org/10.1016/j.emc.2019.03.001 emed.theclinics.com
0733-8627/19/ª 2019 Elsevier Inc. All rights reserved.
2 Urdaneta & Bhalla

Scale (NIHSS) score and noncontrast head CT. An NIHSS score calculation is critical for
all patients suspected of AIS and before any therapy is started, but EM physicians should
not replace a comprehensive neurologic examination with the NIHSS. Intravenous
thrombolytic (IVT) therapy with a tissue plasminogen activator (tPA), given within
4.5 hours of AIS onset, is the mainstay therapy. Endovascular therapy is a recent addition
to the treatment armamentarium that is safe and improves neurologic outcomes.

DIAGNOSIS

Correct and timely identification of an AIS allows for appropriate time-dependent ther-
apies to be initiated, providing the best opportunity for improved functional outcomes.
Common stroke signs and symptoms are discussed in Table 1.
Stroke symptoms can be subtle, and the 2 most commonly missed strokes are pos-
terior circulation strokes and those with low NIHSS scores8; 35% of patients present-
ing with dizziness were misdiagnosed as not having an AIS,9 and patients with an
emergency department (ED) discharge diagnosis of benign dizziness were at a 50-

Table 1
Common stroke symptoms

Vascular Territory Physical Examination Findings

Anterior cerebral artery Contralateral motor deficits
Contralateral sensory deficits
Gait apraxia
MCA Aphasia (expressive and receptive)
Contralateral motor deficits
Contralateral sensory deficits
Homonymous hemianopia
Neglect
Posterior cerebral artery Alexia (inability to read)
Choreoathetosis
Cranial nerve III palsy
Motor deficits
Sensory deficits
Visual disturbances
Vertebrobasilar artery Ataxia
Cranial nerve palsies
Coma
Dizziness with nausea and vomiting
Dysarthria
Dysphagia
Motor deficits with contralateral sensory deficits
Posterior inferior cerebellar artery Ataxia—ipsilateral
Contralateral limb with ipsilateral face pain
Cranial nerve IX and X palsy
Dysmetria
Ipsilateral Horner syndrome
Nystagmus
Vertigo
Anterior inferior cerebellar artery Cranial nerves V and VII palsy
Ipsilateral Horner syndrome
Motor deficit of the face
Nystagmus
Vertigo
 Cutting Edge Acute Ischemic Stroke Management 3

fold increase in stroke admission within the next 7 days.10 Thus, having a good under-
standing of signs and symptoms of posterior circulation stroke is essential for an EM
physician. Key to this is being able to differentiate peripheral from central causes of
dizziness. In their review, Kerber and Newman-Toker9 identified the eye movement ex-
amination as the best discriminator between peripheral and central causes of dizzi-
ness. The eye examination may be the only clue of a posterior circulation stroke,
because the general neurologic examination can be normal in 80% of these stroke pa-
tients.11 Table 2 compares common abnormal eye movement features of a central
versus a peripheral cause of dizziness.
Although the distinction of AIS secondary to large vessel occlusion (LVO) versus
other causes (ie, lacunar stroke) does not affect the decision of IVT therapy, recognition
of symptoms from LVO can help clinicians with the decision of advanced neuroimaging
study (discussed later). LVO is defined as an occlusion of the anterior cerebral artery,
basilar artery, carotid terminus, middle cerebral artery (MCA), and/or posterior cerebral
artery. A left-sided LVO can present with right sided deficits and aphasia, whereas a
right-sided LVO can present with left-sided deficits and neglect. A basilar artery occlu-
sion can lead to a locked-in state where the patient is conscious and able to feel touch
but unable to move anything except the eyes in the vertical plane; branches of the
basilar artery occlusion can present with nausea vomiting and dizziness.

IMAGING
Computed Tomography/CT Angiography
Rapid neuroimaging plays an integral component in AIS management because it pro-
vides information on both stroke subtypes and eligibility for therapy. A current target
time to imaging is 20 minutes from ED arrival for candidates for IVT or endovascular
therapy. Noncontrast head CT is the preferred imaging modality for speed of acquisi-
tion, availability, cost-effectiveness, and high sensitivity for ruling out hemorrhage.12
Other CT findings, such as early infarct signs and evidence of mass lesions, also
may help guide early diagnosis and therapy.13 If there is any suspicion of an LVO,
CT angiogram (CTA) of head and neck should be obtained as long as last known
normal is less than 24 hours. By using iodinated radiocontrast media to image intra-
cranial and extracranial blood vessels, the location of the occlusive thrombus can
be determined, and other features, such as tandem lesions, can be identified to facil-
itate preprocedural planning.14 Additionally, CTA of head may provide information on
collateral supply to the ischemic territory, with good collateral supply distal to the oc-
clusion associated with positive clinical outcomes.15 Inclusion of aortic arch in CTA of
neck can identify atherosclerosis as well as rare but devastating type A aortic dissec-
tion as a potential cause of AIS.

Table 2
Comparison of central versus peripheral cause of dizziness

Peripheral Central
Transient (lasting <30 s) vertical-torsional Persistent spontaneous or gaze evoked
nystagmus triggered by positional testing vertical or torsional nystagmus
Unidirectional horizontal nystagmus during Persistent horizontal gaze-evoked
gaze testing that never changes direction direction- changing nystagmus
with gaze direction shifts or head shaking,
but changes velocity with gaze direction shift
Nonfatiguing downbeat nystagmus
triggered by positional testing
4 Urdaneta & Bhalla

MRI/MR Angiography
MRI can provide a wealth of information in AIS but may be difficult to obtain without
increasing door-to-needle (DTN) time.16 Diffusion-weighted imaging (DWI) provides
the most accurate measure of infarct core volume, shows early ischemic changes
within minutes, and is the optimal study to evaluate posterior circulation infarcts.15
Susceptibility-weighted imaging (SWI) can be used to assess for hemorrhage and ce-
rebral microbleeds unseen on head CT, whereas fluid-attenuated inversion recovery
(FLAIR) sequences can be used to assess brain parenchyma. An absence of hyperin-
tensity in the region of infarct on FLAIR indicates that the stroke is less than 4.5 hours.17
Time-of-flight or contrast-enhanced MR angiogram can be used to assess the intra-
cranial and extracranial vasculature analogous to CTA (Fig. 1).

Perfusion Imaging
After vascular occlusion, the 3-compartment theory differentiates brain paren-
chyma into 3 categories: (1) the infarct core, which represents nonviable brain tis-
sue, which cannot be salvaged; (2) the penumbra, which represents tissue that has
reduced blood flow, but the potential for survival if blood flow is restored; and (3)
the outer zone, which survives regardless of treatment. Recent endovascular ther-
apy trials utilized perfusion imaging techniques to identify patients with a mismatch
between the volume of hypoperfused tissue and the volume of nonsalvageable
infarct core.

Fig. 1. An 85-year-old man with a history of multiple strokes and history of left-sided weak-
ness presented with worsening weakness of his left side. Upper left panel shows MRI image
with a hyperintense region on the DWI sequence with lower left panel showing the corre-
sponding dark region on the apparent diffusion coefficient (ADC). The upper right panel
shows the FLAIR sequence with a hyperintense area in the same region indicating the stroke
is older than 4.5 hours. Finally, the lower right panel shows the SWI image with a hyperdense
area within the stroke indicative of hemorrhage into the stroke.
 Cutting Edge Acute Ischemic Stroke Management 5

Perfusion imaging can be performed by CT or MRI, and both use the same basic
concepts to measure the time it takes for blood to reach brain tissue (time to peak
of the residual function [Tmax] and mean transit time [MTT]) and the amount of blood
flowing through the brain vasculature, including capillary and venular flow (cerebral
blood volume [CBV] and cerebral blood flow [CBF]). Tmax is the time it takes the
contrast to reach maximum enhancement in the selected region of interest. MTT re-
flects the time between the arterial inflow and the venous outflow. CBV is the volume
of blood available per unit of brain tissue (Fig. 2). To simplify interpretation, recent
endovascular trials used software (Rapid, iSchemaView, Menlo Park, California) for
postprocessing of the images. This software defined a relative CBF less than 30%
of normal brain as a marker of irreversible injury (infarct core) and defined the penum-
bral volume as tissue with a Tmax greater than 6 seconds (Fig. 3).18,19 CT perfusion
uses iodinated contrast whereas magnetic resonance perfusion uses gadolinium to
achieve these measurements. The acquisition and processing of perfusion images
take time and expose patients to additional iodinated contrast and radiation; an algo-
rithm for obtaining different studies are outlined in Fig. 4.

STROKE MANAGEMENT
Tissue Plasminogen Activator Updates and Controversies
Currently, the only Food and Drug Administration (FDA)-approved therapy for AIS is
alteplase, at a dose of 0.9 mg/kg. The inclusion and exclusion criteria for administra-
tion of alteplase are reviewed elsewhere.5,7 This dose of tPA has been shown to in-
crease the chance of having independent function 3 months after AIS by greater
than 30%,5 yet there remains skepticism within the EM community of the benefits
versus harm of alteplase.
A meta-analysis looking at the standard dose of alteplase demonstrated that alte-
plase was associated with a 1.5% greater absolute risk of clinically significant intracra-
nial hemorrhage (ICH) in patients with NIHSS scores between 0 and 4 and with a 3.7%
greater absolute risk in patients with NIHSS score greater than 22 strokes compared
with those not treated with alteplase. This increase in ICH was associated with a 2.3%
absolute increase in deaths within 7 days.20 These numbers present a real concern for
the administration of alteplase but are outweighed by the benefits of alteplase admin-
istration. In patients with NIHSS score 0 to 4 stroke, alteplase had an absolute in-
crease in excellent outcome by 8%, and for all strokes had an absolute increase in

Fig. 2. CT perfusion maps of an 87-year-old man who presented with an NIHSS of 20 approxi-
mately 13.5 hours after last known well. In the figure, the first image is the Perf BL, second image
is rCBV, third image is rCBF, fourth image is MTT, and fifth image is Tmax., In the third image, the
dark blue area (circled in red) demonstrates tissue with low CBF (infarct core), whereas the
circled area on the fifth image indicates areas where the blood is taking a longer time to reach
maximum Hounsfield units (salvageable tissue). MTT, mean transit time; Perf BL, perfusion; rCBF,
relative cerberal blood flow; rCBV, relative cerebral blood volume; Tmax, time to peak of the
residual function.
6 Urdaneta & Bhalla

Fig. 3. MRI perfusion scan, which has been processed by the RAPID software. A 64-year-old
man presented 7 hours after the last known well with a NIHSS of 16. The processed image
shows an infarct core volume of 7 mL (pink), and a penumbal volume of 105 mL (green).

the chance of an excellent outcome by 6.8%.20 Patients and family should be informed
of the risks of alteplase administration, but the EM physician should not withhold, or
dissuade the decision maker against, the administration of alteplase.
An additional concern that is cited regarding tPA administration is its administration
to patients on antiplatelet therapy (APT). Although tPA administration to a patient on
APT is associated with an absolute increase in ICH of 4.5%, this increase in ICH is
not associated with an increase in fatal ICH within 7 days or an increase in 30-day mor-
tality.21 Additionally, tPA administration to those on APT demonstrated a slight trend
toward improved functional outcome compared with those on APT who were not
treated with tPA.21,22 These findings also were found for patients taking dual APT.23
Given these data, tPA should not be withheld for those on APT or dual APT.

Fig. 4. Imaging decision algorithm. CTP, CT perfusion; EVT, endovascular therapy; LKN, last
known normal; NCT, noncontrast CT; TPA, tissue plasminogen activator.
 Cutting Edge Acute Ischemic Stroke Management 7

In the United States, tPA is recommended for patients greater than 80 years of age
with AIS onset within 3 hours. There are no current recommendations for those
greater than 80 years of age in the 3-hour to 4.5-hour onset window. The only study
of patients greater than 80 years of age looked at the outcomes for patients who
were given tPA in the less than 3-hour window compared with those who were given
tPA in the 3-hour to 4.5-hour window. There was a 1.7% increase in ICH rate in the 3-
hour to 4.5-hour treatment group compared with the 3-hour treatment group, but no
difference in mortality or functional outcome at 3 months between the 2 groups.24
Although there is a paucity of data on the subject, tPA should not be withheld in
AIS for patients greater than 80 year old as long as it is within the 4.5-hour onset
window.
Given the risk of ICH with administration of alteplase, several studies have attemp-
ted to examine if lower doses of alteplase would produce lower rates of ICH. The
ENCHANTED was a noninferiority trial that looked at standard-dose alteplase
(0.9 mg/kg) compared with low-dose alteplase (0.6 mg/kg). Because the studies
were unable to demonstrate noninferiority of low-dose alteplase,25,26 standard-dose
alteplase at 0.9 mg/kg should be continued to be administered until further research
demonstrates otherwise.

Tenecteplase
Alteplase is the current standard tPA for AIS. A potential alternative agent is tenecte-
plase, a bioengineered tPA that has a longer half-life than alteplase, allowing it to be
delivered as a bolus, and has more specificity for fibrin and greater resistance against
the plasminogen activator inhibitor.27–30 Although some studies have shown tenecte-
plase to have superior recanalization rates and functional outcomes,27,30,31 others
have failed to demonstrate such differences.28,29 Further research is needed before
tenecteplase is considered for AIS.

Extended Window Intravenous Thrombolytic Therapy

In the WAKE-UP trial, MRI was utilized to identify patients who qualify for intravenous
(IV) alteplase in patients with neurologic deficits on waking from sleep.32 Patients
who had a lesion on DWI without a corresponding lesion on the FLAIR sequence
were treated with IV alteplase. The trial was stopped due to a lack of funding, but
interim analysis showed treatment with IV alteplase was associated with a higher
likelihood of an outcome with no or minimal neurologic deficit at 90 days compared
with placebo. The rates of symptomatic intracerebral hemorrhage and death at
90 days, however, were higher with IV alteplase than with placebo. Although it is a
promising study, further studies are needed before MRI-guided thrombolysis is
recommended.

ENDOVASCULAR MECHANICAL THROMBECTOMY

Background
Since 2015, endovascular therapy has revolutionized AIS management in patients with
LVO. Historically, treatment options were limited to IVT therapy, which only achieves
recanalization in less than 30% and good clinical outcome in 25% of patients with
LVO.33 For patients who presented greater than 4.5 hours after the stroke symptoms,
treatment options were limited even more.
Early investigations with intra-arterial therapies utilized local thrombolytic34,35
and subsequently clot removal devices.36,37 In 2015, the Multicenter Randomized
Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the
8 Urdaneta & Bhalla

Netherlands (MR CLEAN), comparing thrombectomy to standard of care, demon-

strated improved outcome at 90 days without an increase in symptomatic ICH or
mortality.38 After this study, several other studies (Extend-IA, ESCAPE, SWIFT
PRIME, and REVASCAPT) 18,39–41 were terminated early after interim analysis
demonstrated overwhelming efficacy of thrombectomy. Based on evidence from
these trials, practice guidelines were updated recommending that endovascular
therapy should be provided to patients within 6 hours of symptom onset plus oc-
clusion of the internal carotid artery or proximal MCA regardless of the use of
IVT therapy.

Extended Window Trials

In 2018, 2 large multicenter trials were published, which extended the time window
for endovascular therapy: the DAWN and DEFUSE3 trials.19,42 The DAWN trial
enrolled patients up to 24 hours from symptom onset and restricted thrombectomy
to the use of the Trevo device (STRYKER, Kalamazoo, MI), whereas DEFUSE3
allowed all FDA-approved devices and enrolled patients who presented within
16 hours of last known normal. Both trials required the use of advanced neuroimag-
ing to capture patients who had a significant mismatch between infarcted core and
hypoperfused tissue, with both trials showing better functional outcomes at
90 days.19,42 Table 3 demonstrates the key difference between the 2 studies.
Based on these 2 studies, the American Heart Association (AHA) updated their
stroke guidelines. Box 1 lists the updated AHA recommendations for endovascular
therapy.

Table 3
Characteristics of DAWN and DEFUSE-3 trials

DAWN DEFUSE-3
Clinical inclusion criteria Clinical inclusion criteria
Age 18 Age 18–90 y
Baseline NIHSS score 10 Baseline NIHSS score 6
Prestroke mRS <2 Prestroke mRS 2
Anticipated life expectancy
6 mo
Ineligible for IV tPA
Eligible 6–24 h after last seen well Eligible 6–16 h after last seen well
Occlusion of intracranial Occlusion of extracranial or intracranial
ICA or proximal MCA ICA or proximal MCA
Group A: >80 y, NIHSS 10; Infarct volume <70 mL
infarct volume <21 mL 1 ratio of volume of ischemic tissue to initial
Group B: <80 y; NIHSS 10; infarct volume of 1.8
infarct volume <31 mL
Group C: <80 y; NIHSS 20;
infarct volume 31 mL to <51 mL
CT or magnetic resonance–based CT or magnetic resonance–based imaging
imaging
Rapid software for image analysis Rapid software for image analysis
Only Trevo (Stryker, All FDA-approved devices for recanalization allowed
Kalamazoo, MI) device allowed
for recanalization
Sponsored by Stryker Sponsored by National Institutes of Health
(Kalamazoo, MI)
 Cutting Edge Acute Ischemic Stroke Management 9

Box 1
Summary of American Heart Association acute ischemic stroke guidelines related to
endovascular therapy

IVT should not be withheld regardless of whether EVT is considered, and EVT should not be
delayed assessing for a clinical response to IVT.
EVT therapy with a stent retriever device should be performed if
1. The procedure can begin within 6 hours of symptom onset
2. Baseline functional status of mRS 0 to 1
3. M1 or ICA occlusion on CTA
4. Age 18 years old, ASPECTS  6 and NIHSS 6
Patients with an LVO in the anterior circulation maybe a candidate for EVT if
1. LKN 6 hours to 16 hours and they meet eligibility criteria for DAWN38 or DEFUSE 339
2. LKN 16 hours to 24 hours and they meet eligibility criteria for DAWN38
It also can provide an estimate of ischemic tissue by applying the ASPECTS, a 10-point score that
subtracts a point for each predefined region of parenchymal hypoattenuation within the ante-
rior circulation. 14
Abbreviations: ASPECTS, Alberta Stroke Program Early CT Score; EVT, endovascular therapy; LKN,
last known normal; mRS, modified Rankin score; M1, 1st segment of middle cerebral artery.

Data from Powers WJ, Rabinstein AA, Ackerson T, et al. 2018 Guidelines for the early manage-
ment of patients with acute ischemic stroke: a guideline for healthcare professionals from the
American Heart Association/American Stroke Association. Stroke 2018;49(3): p. e46–110.

OTHER MEDICAL MANAGEMENT AND MONITORING

As with all acutely ill patients, the ABCs need to be assessed and addressed. All pa-
tients with AIS who undergo an intervention need to be admitted and monitored in a
dedicated stroke unit. More specific management recommendations are discussed.

Blood Pressure
Approximately 75% of patients who present to the ED with AIS have an elevated sys-
tolic blood pressure (SBP) greater than 140 mm Hg. There are strict blood pressure
(BP) recommendations for patients with AIS who are to undergo tPA administration
or endovascular therapy. Prior to any therapy, the SBP should be lowered to less
than 185 mm Hg and diastolic BP (DBP) less than 110 mm Hg. Once therapy has
started, the BP should be maintained less than 180/105 mm Hg for the following
24 hours. During tPA administration, the BP must be measured every 15 minutes for
2 hours, every 30 minutes for 6 hours, and then every hour for the next 16 hours.13
Short-acting titratable agents, such as labetalol, nicardipine, and clevidipine, should
be used to achieve the BP goals.
The current AHA guidelines do not address SBP goals in patients with AIS not
eligible for tPA or endovascular therapy.13 Studies looking at aggressive BP control
have not demonstrated a mortality or functional outcome benefit.43 Excessive reduc-
tion of BP in AIS can lead to hypoperfusion of at-risk brain tissue due to loss of cere-
bral autoregulation and further enlarge the ischemic territory. Thus, in patients who do
not receive tPA or endovascular therapy, it is reasonable to attempt a 15% reduction
in BP over the first 24 hours when the SBP is greater than 220 mm Hg or DBP is greater
than 120 mm Hg. 44
Hypotension should be corrected with volume repletion and then vasopressors, but
no recommendation for a lower limit of SBP goal exists in the literature. Given that no
recommendation exists, it is reasonable to aim for a mean arterial pressure goal
10 Urdaneta & Bhalla

greater than 65 mm Hg, as is done with other patients in shock, and adjust as needed
based on the adequacy of end-organ perfusion.

Temperature Management
Hyperthermia has been associated with an increased mortality and worse neurologic
outcomes in AIS.15 Measures should be taken to treat hyperthermia, but there are no
specific guidelines to dictate how to achieve this goal. Reasonable options include the
use of antipyretics and active cooling to normothermia. The use of therapeutic hypo-
thermia for AIS has not been established and the current 2018 AHA guidelines state
that therapeutic hypothermia should be conducted on a research basis only. 13

Blood Glucose
Measurement of blood glucose is an absolute requirement before the administration of
tPA because hypoglycemia can mimic the examination findings in AIS.13 Hypoglycemia
also can worsen functional outcomes in AIS. Conversely, hyperglycemia has been
shown to increase neuronal apoptosis and cerebral edema, resulting in worse functional
outcome.45 Therefore, an emphasis should be placed on prevention of hypoglycemia
while correcting hyperglycemia. The 2018 AHA guidelines recommend aiming for blood
glucose between 140 mg/dL and 180 mg/dL for all patients with ischemic stroke. 13

Oxygen
Hypoxemia is believed to lead to further injury of ischemic tissue in the penumbral re-
gion of the stroke and should be avoided; on the other hand, there is no role for the
administration of prophylactic oxygen administration in AIS patients without hypox-
ia.46 Thus, supplemental oxygen should be administered only to AIS patients whose
pulse -oximetry is less than or equal to 94%.

Tissue Plasminogen Activator Complications

The 2 most common life-threatening complications of tPA administration are ICH and
angioedema. Angioedema is found to affect primarily the orolingual region and is more
strongly associated with patients taking angiotensin-converting enzyme inhibitor.
Signs and symptoms of ICH from tPA administration are listed in Box 2. Once ICH
is suspected, tPA should be stopped and immediate noncontrast head CT should
be performed. Treatment of tPA-associated ICH includes stopping the tPA administra-
tion, close monitoring of the airway, and supportive care. Although there are no quality
studies to support the use of cryoprecipitates and antifibrinolytics to reverse the ef-
fects of tPA, several societies recommend these agents47 and, based on these recom-
mendations, reversal should be considered.

Box 2
Signs/symptoms of intracranial hemorrhage associated with tissue plasminogen activator
administration

Change in level of consciousness

Change in pupil size and reactivity
New-onset nausea and vomiting
New-onset severe headache
Worsening hypertension
 Cutting Edge Acute Ischemic Stroke Management 11

SYSTEMS OF CARE AND PROCESS IMPROVEMENT

With the success of recent extended window trials, the number of patients eligible for
endovascular therapy is expected to increase. Despite the extended time windows, it
is still evident that faster treatment times are beneficial for both IVT and endovascular
therapy.48,49 Quality-improvement initiatives should be implemented in each
hospital to decrease the DTN times. The Helsinki model achieved a median DTN
time of 20 minutes without an increase in complications.50,51 Some key components
of this model are (1) EMS prenotification with patient details activating a stroke team to
meet the patient on arrival, (2) direct transfer of patients from triage to the CT table on
the ambulance stretcher, and (3) IVT administered in CT scanner after rapid reading of
imaging by stroke neurologist.
Because many hospitals are not equipped with capabilities to perform endovascular
therapy, a local protocol should be developed to achieve a prompt transfer of patients
with potential eligibility for endovascular therapy. Thus, a crucial question is, What is
the most time-efficient model for transfer for AIS patients eligible for endovascular
therapy? Currently, there are 4 organizational models for intra-arterial treatment,
which have been described: mother-ship, drip-and-ship, trip-and-treat, and mobile
stroke unit model. 52
In the mother-ship model, patients are transported directly to the nearest compre-
hensive stroke center (CSC), bypassing any primary stroke center (PSC), and thus is
dependent on accurate identification of LVO by EMS to avoid overuse of resources
as well as time delays in patients eligible for IVT but not endovascular therapy. A recent
study evaluated 13 validated prehospital scales used to identify patients with LVO and
determined that with the standard cutoffs there was high accuracy but greater than or
equal to 20% of patients would be routed incorrectly away from a CSC. 53
In the drip-and-ship model, patients are taken to the nearest PSC, treated with IVT if
indicated, and transferred to a CSC if an LVO is identified on vessel imaging. In this
model, the door-in to door-out time at the PSC has been identified as a significant
component of total transfer time; thus, efficient workflows are crucial for patient out-
comes. 29
For both models, telemedicine is an accepted method for decision making.
Experienced stroke neurologists can provide consultation to PSCs or prehospital
care providers in the ambulance.54 A recent study described a health care
network that used a modified Helsinki protocol and a centralized telemedicine
approach to improve both the DTN times and the amount of people treated with
IVT. 55
The trip-and-treat model was evaluated in New York City, where a mobile interven-
tional stroke team traveled to 4 PSCs within the city to provide onsite interventional
services. In this urban environment, there was shorter time-to-treatment for endovas-
cular therapy compared with the drip-and-ship model56; however, it remains to be
seen if this is reproducible in suburban or rural communities.
A mobile stroke unit is essentially an ambulance equipped with at least
a CT scanner, telemedicine capabilities, and a point-of-care laboratory system
to make hyperacute ischemic stroke decisions in the field. In Germany,
where this model has been utilized the most, there has been an increase in IVT
rates, with significantly shorter time to treatment compared with conventional
care. 57
Although there are ongoing studies evaluating these models, it is likely that the best
model will be dependent on factors specific to the region, such as geography, local
infrastructure, population density, transportation times, and distribution of centers.
12 Urdaneta & Bhalla

SUMMARY

Prompt recognition of AIS symptoms is a critical step to ensuring the delivery of time-
dependent therapies in the ED. Posterior circulation stroke presenting with dizziness
may be mistaken for peripheral causes, and focused eye examination should be uti-
lized to help distinguish the 2. Unless contraindicated, IV tPA should be considered
in all patients within 4.5 hours of symptom onset, including in patients greater than
80 years or on APT. Eligibility of endovascular therapy should be evaluated for any pa-
tient with AIS presenting within 24 hours of symptom onset by utilizing clinical suspi-
cion for LVO and advanced neuroimaging. Regardless of the eligibility of tPA and
endovascular therapy, patients with AIS should receive appropriate supportive care
to meet BP, glucose, temperature, and oxygen goals. Finally, each hospital should
develop a protocol to improve DTN time and efficiency of the transfer process to a
CSC for eligible patients.

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