Neurocrit Care

https://doi.org/10.1007/s12028-019-00811-7

ACUTE ISCHEMIC STROKE

Emergency Neurological Life Support: Acute

Ischemic Stroke
Noah Grose1*, Archana Hinduja2*, Deborah S. Tran3,4 and Aaron Raleigh5

© 2019 Neurocritical Care Society

Abstract 
Acute ischemic stroke (AIS) is a neurological emergency that can be treated with time-sensitive interventions, includ-
ing both intravenous thrombolysis and endovascular approaches for thrombus removal. Numerous studies have
demonstrated that rapid, protocolized assessment and treatment is essential to improving neurological outcomes.
For this reason, management of AIS was chosen as an Emergency Neurological Life Support protocol. The protocol
focuses on the early identification and initial management, within the first hour(s) following acute onset of a neuro-
logical deficit. The highlights of this module include identification of AIS using prehospital stroke scales, prehospital
triage and transportation of a suspected stroke, an algorithm for emergent evaluation of AIS with target benchmarks,
updated inclusion and exclusion criteria for intravenous thrombolytic use, selection criteria for endovascular therapy,
and early management of patients with AIS and transient ischemic attack who are not candidates for intravenous
thrombolysis or endovascular therapy.
Keywords:  Ischemic stroke, Endovascular therapy, Transient ischemic attack, tPA

Introduction Management Protocol

According to the 2017 World Health Organization statis- The Emergency Neurological Life Support (ENLS) algo-
tics, cerebrovascular disease is the second leading cause rithm for initial management of acute ischemic stroke
of death worldwide, with an estimated 6.3 million deaths (AIS) is shown in Fig.  1. Suggested items to complete
per year (compared to 8.7 million deaths annually due to within the first hour of evaluating a patient with AIS are
ischemic heart diseases), and one of the leading causes of given in Table  1. The most important information that
disability [1]. In the USA, approximately 795,000 strokes guides therapy is the last known well (LKW) time or time
occur annually, of which nearly 25% are recurrent strokes of symptom onset. All patients with LKW time < 24  h
[2]. Stroke is the fifth most common cause of death and should be emergently evaluated for an AIS. Thrombo-
the leading cause of disability in the USA. Although there lytics should be administered to all patients with LKW
have been many new advances in the treatment of stroke, time < 4.5  h that meet the inclusion and exclusion cri-
it is crucial that proper diagnosis and management occur teria. All patients < 24 h of symptom onset who have an
as soon as possible, since delays in therapy are associated National Institutes of Health Stroke Scale (NIHSS) ≥ 6
with worse neurological recovery [3]. should be evaluated with CT angiogram/CT perfusion
(CTA/CTP) or multimodal magnetic resonance imaging
(MRI) including diffusion-weighted imaging (DWI) and
perfusion-weighted imaging (PWI) with intracranial ves-
sel imaging for the presence of a large vessel occlusion
*Correspondence: [email protected]; [email protected]
1
Mount Carmel College of Nursing, Adult Gerontological Acute Care (LVO). If the patient has an LVO and favorable perfusion
Nurse Practitioner Program, Columbus, OH, USA studies, they should be emergently taken for endovas-
2
Department of Neurology, The Ohio State University Wexner Medical
cular intervention or transferred to a facility for this. In
Center, Columbus, OH, USA
Full list of author information is available at the end of the article patients that have complete resolution of symptoms upon
 Fig. 1  ENLS acute ischemic stroke (AIS) protocol. The AIS algorithm is a broad overview of the initial evaluation of an acute stroke patient and is a
quick reference for the major treatment options

Table 1  Acute ischemic stroke checklist for the first hour Prehospital Considerations
□ Activate stroke code system (if available)
The prehospital providers play a key role in the multidis-
□ Vital signs
ciplinary effort in assessing, transporting, and providing
□ Supplemental oxygen to maintain saturation   ≥ 94%
timely acute care for an AIS patient. Providers should
□ Determine time of onset/last known well (LKW)
always err on the side of caution in triaging patients to
□ Determine NIHSS score
stroke receiving facilities, utilizing emergent ground and
□ CT, CTA​
air transport and resources. Stroke receiving facilities
□ Medication l­ista
should be active in working with local emergency medi-
□ IV access—18 g peripheral IV
cal services (EMS), regulatory agencies and providers to
□ Laboratory tests: fingerstick glucose, CBC with platelets, PT/INR, PTT,
ensure continuity of care, and best practices across all
levels of care for the AIS patient.
□ EKG
and beta-HCG for women of childbearing age

a Clinical Suspicion of Stroke and Prehospital Transportation

  When asking about medications, be sure to ask specifically about
anticoagulants and when medication was last taken/administered Acute stroke is suspected when a patient exhibits the
CBC complete blood count, CT computed tomography, CTA​ CT angiogram, EKG sudden onset of a focal neurological deficit (e.g., facial
electrocardiogram, HCG human chorionic gonadotropin, INR international droop, arm/leg weakness, ataxia, sudden onset vertigo or
normalized ratio, LKW last known well, NIHSS National Institutes of Health Stroke
Scale, PT prothrombin time, PTT partial thromboplastin time dizziness, aphasia, dysarthria, vision disturbances, gaze
preference, sensory disturbances, neglect, or other focal
findings). In the absence of an obvious seizure, the deficit
evaluation, expedited workup for a transient ischemic can most likely be attributed to stroke or TIA. The time
attack (TIA) should be initiated. from symptom onset to arrival at an emergency depart-
ment (ED) is the greatest source of delay and a frequent
 ••  Time between the receipt of the call and dispatch of
the EMSS team is < 90 s.
••  EMSS response time is <  8  min (time elapsed
from the call receipt to arrival on the scene by the
equipped and staffed ambulance).
••  The on-scene time is < 15  min (barring extenuating
circumstances such as extrication difficulties).
••  Travel time expectation is equivalent to trauma or
acute myocardial infarction calls.

Standard treatments for EMSS are to perform rou-

tine airway, breathing, and circulation (ABC) assess-
ments; administer supplemental oxygen as needed; check
blood/capillary glucose and treat hypoglycemia (glucose
< 60  mg/dl); and perform a validated stroke severity
scale examination [e.g., Field Assessment Stroke Triage
for Emergency Destination (FAST-ED) [5], Rapid Arte-
rial Occlusion Evaluation (RACE) [6], and Los Angeles
Motor Scale (LAMS) [7]]. Personnel should obtain IV
access (ideally 18 g placed antecubitally to facilitate con-
trast imaging). Last known well time or symptom onset
is the most critical component of the history in a patient
with AIS, and every effort should be made to establish
this while balancing the on-scene time guidelines and
without delaying transport time. Thus, a strong consid-
eration should be made to either bring any witness in the
ambulance, or have their contact information available
for the ED staff. Prehospital systems should call ahead to
the receiving hospital, and patients should preferentially
be transported to the appropriate certified stroke center
(Table 2) [4].
Patients may have a stroke while in the hospital, at
Fig. 2  Clinical suspicion of stroke algorithm: This algorithm assumes
rehabilitation centers, or nursing homes, or may present
the patient is outside of the hospital when stroke occurs. Based on
the results of brain imaging, the patient can be triaged to one of the directly to an ED triage. Nurses or Advanced Practice
three ENLS protocols (bottom): subarachnoid hemorrhage, intracra- Providers (APPs) may be the first healthcare providers
nial hemorrhage, or acute ischemic stroke to have contact with the patient in these circumstances;
therefore, it is important for them to recognize and
respond quickly and appropriately. In cases of uncer-
tainty, with respect to whether a patient is having a stroke
cause of ineligibility for reperfusion therapies [4]. In
and stroke team activation is necessary, the simple man-
countries that treat stroke as an emergency, prehospital
tra “If in doubt, call it out” is best.
personnel are typically the first to evaluate the patient in
the home or at a scene (Fig.  2). Patients with suspected
acute stroke should be triaged with the same priority as
Emergency Department
serious trauma or acute myocardial infarction, regardless
Diagnosis
of the severity of deficit. The “Implementation of Strat-
Immediately on arrival to an ED, patients should be
egies for Emergency Medical Services Within Stroke
screened for stability, undergo rapid clinical stroke
Systems of Care” policy statement outlines specific
assessment (“at the door”), and then be taken directly for
parameters for the Emergency Medical Services Systems
rapid imaging, with non-contrast computed tomography
(EMSS) [4]:
(CT). Noninvasive CTA should be obtained as quickly as
possible to expedite the identification of LVO. These are
••  Stroke patients are dispatched at the highest level of
often completed in succession, but should not delay the
care available in the shortest time possible.
administration of thrombolytics for eligible patients [8,
Table 2  Prehospital standard assessment and treatment

□ Perform history and physical examination

□ Determine time patient was last known well (LKW)
□ ABCs (routine airway, breathing, and circulation assessments)
□ Administer supplemental oxygen as needed
□ Check blood/capillary glucose
□ Perform a stroke severity scale examination
□ Obtain intravenous (IV) access
□ Obtain blood tubes vials for evaluation at the receiving stroke center (optional)
□ Transport the patient to the closest certified stroke center
□ Activate prehospital notification
□ To decrease door to imaging time, strongly consider a brief doorway assessment on arrival to the ED and take the patient to brain imaging on the
EMS gurney
ED emergency department, EMS emergency medical services

9]. Some centers use abbreviated/accelerated MRI, mag- Currently, there are no recommendations from the
netic resonance angiogram (MRA), and MR perfusion American Heart Association/American Stroke Associa-
instead of CT. tion (AHA/ASA) on the time for evaluation of patients
In the USA, the Joint Commission (TJC) has recom- and transfer from an outside hospital to the receiving
mended benchmark metrics for acute evaluation and hospital for endovascular therapy. Delays in evaluating,
treatment of the acute stroke patient. Similarly, ENLS treating, and transferring an AIS patient to an accepting
recommends targeting goals based on the metrics out- hospital should be minimized. One method to accom-
lined by the respective local or national organizations. plish this is for primary stroke centers to establish ongo-
ing transfer agreements with nearby comprehensive or
Interval Target endovascular-ready hospitals. Protocols for interhospital
Door-to-provider 10 min
transfer of patients should be established and approved
Access to neurological expertise 15 min
beforehand so that efficient patient transfers can be
Door-to-CT completion 20 min (in at least 50% of patients)
accomplished at all hours of the day and night [4].
Door-to-CT interpretation 45 min
As shown in Fig. 2, imaging is essential to confirm the
Door-to-IV thrombolytics 60 min (primary objective)
correct diagnosis and exclude intracranial hemorrhage. If
45 min (secondary objective) non-contrast CT head is negative for hemorrhage, an AIS
Door-to-puncture time for endovas- 90 min or TIA must be considered for acute onset of neurologi-
cular intervention cal symptoms.
Door-to-recanalization 120 min When confronted with a patient whose focal neuro-
Admission to stroke unit or ICU 3 h logical symptoms have begun within the preceding few
hours, it should be assumed that the patient would even-
Utilization of “telestroke” networks (hub-and-spoke tually be diagnosed with stroke. Most TIAs are brief, typi-
model) is helping  to solve the shortage of neurologists cally lasting less than 20 min before completely resolving.
in rural areas and has demonstrated high rates of safe Therefore, if the patient is still manifesting physical signs
administration of thrombolytics while decreasing time of a stroke in the ED, those signs must be managed as if
to initiate thrombolytics [10, 11]. Hemorrhage, mortality the patient is having an active stroke.
rates, and functional outcomes are comparable to rand- In some centers, patients may be screened for clini-
omized trials of patients treated live at study sites. Many cal stability immediately upon arrival (“at the door”) and
regional arrangements have been made for “telestroke” taken directly to CT based on clinical symptoms suspi-
consultation in order to expedite the administration of cious for acute stroke. However, there are a number of
thrombolytic therapy in the “drip-and-ship” model fol- stroke mimics including seizure, hypoglycemia, sep-
lowed by transfer to a higher-level certified stroke center sis, fever, migraines, and Bell’s palsy. Given that treat-
if necessary or possible. If patients are eligible for throm- ment of AIS is time sensitive, it is not uncommon for
bolysis, it should be administered prior to transport. patients with stroke mimics to be treated with throm-
Transport of patients from spoke to hub (originating to bolysis. Stroke mimics should be ruled out as best pos-
destination site) may involve air medical transport. sible; however, if mimics are inadvertently treated with
thrombolytics, there seems to be minimal risk of adverse due to poor perfusion of previously injured tissue. It is
effects associated with their utilization [3, 12]. Ultimately, recommended that hypotension should be corrected to
if the patient is manifesting physical signs of a stroke in maintain systemic perfusion level to support organ func-
the ED and falls within AHA/ASA recommendations, tion [3]. Blood pressures in excess of 220/120  mmHg
then thrombolytics should be offered and administered should be lowered, regardless of the ultimate diagnosis;
[3, 13]. however, allowing permissive hypertension (i.e., allow-
Each of the following elements should be addressed in ing BP to rise naturally) up to 220/120  mmHg for AIS
rapid protocolled succession. patients deemed not to be candidates for thrombolysis,
including those who have failed attempts to lower BP to
Time of Symptom Onset allow eligibility, has been suggested [8].
One of the chief criteria used to select patients for acute If the patient is a potential thrombolysis candidate,
stroke interventions is the patient’s time of stroke onset interventions to control BP should be initiated immedi-
defined as LKW time or alternatively the time of symp- ately. In this manuscript, the term  intravenous throm-
tom onset (if witnessed). Acute stroke treatment thera- bolysis is used to discuss both IV tPA/alteplase and
pies such as thrombolysis are time sensitive, and delays tenecteplase (where applicable). Target BP goal for
can lead to a lower likelihood of a good outcome and patients eligible for IV tPA is < 185/110  mmHg, and
an increased risk of intracranial hemorrhage [14]. The once IV  tPA is initiated, BP must be maintained below
LKW time without neurological deficits must be estab- 180/105  mmHg for 24  h after administration of IV  tPA
lished from the patient or a bystander. If the patient went to limit the risk of intracranial hemorrhage [8]. A strat-
to bed and awoke with the stroke symptoms, the LKW egy for careful BP lowering should be employed while
time is considered to be when the patient went to bed. It ensuring large fluctuations in BP once at goal are lim-
is always worthwhile to ask the patient or family member ited. Short-acting intravenous agents such as labetalol,
about getting up during the night to go to the bathroom nicardipine, clevidipine, urapidil, or hydralazine are pre-
as the information may allow changing the LKW time ferred (see Table  3) to achieve a BP < 180/105  mmHg.
to a more recent time, which may place the patient back Intravenous clonidine is sometimes used, but this is not
into a treatable time window for thrombolysis. available in the USA. Hypertension is common in the set-
Some centers are studying and treating patients who ting of AIS. Titratable IV antihypertensive agents such
wake up with AIS with intravenous alteplase under as labetalol, nicardipine, and clevidipine infusions are
research protocols using advanced imaging techniques to preferred, although urapidil and hydralazine can also be
determine which patients have salvageable tissue and the used for the treatment of hypertension in the acute set-
risk of complications for different treatment modalities ting [3]. There is variability in the specific agent used for
[15–17]. In patients who have had stroke onset < 4.5  h, BP lowering across the world in the acute setting.
the DWI sequence will show the stroke but it will not be If the patient’s BP proves refractory to the above medi-
evident on FLAIR (fluid attenuated inversion recovery) cations, the patient is considered to be high risk of intrac-
sequence of MRI. In the WAKE-UP trial, patients who erebral hemorrhage (ICH) and should not be treated
had presumed stroke onset < 4.5  h based on MRI had a with thrombolysis. However, efforts to reduce BP below
better functional outcome after IV type plasminogen 220/120  mmHg should be continued. Permissive hyper-
activator (tPA) than those who received placebo [18]. tension up to 220/120 mmHg is allowed for TIA, as it is
The results of endovascular therapy in patients with per- for patients who did not receive thrombolytics. This ele-
fusion mismatch on imaging with LVO have also clearly vated blood pressure may be gradually lowered over the
benefited this subset of patients with the DAWN and next 24–48 h [3].
DEFUSE-3 studies [15, 19, 20].
Laboratory Examination
Vital Signs A complete laboratory examination for AIS includes cap-
Pulse oximetry should guide whether the patient needs illary blood glucose (CBG), complete blood count (CBC)
supplemental oxygen to achieve an oxygen saturation with platelets, chemistries, prothrombin time/partial
≥ 94%. Hyperoxia may be detrimental in stroke, so there thromboplastin time (PT/PTT), international normal-
is no need for high-flow oxygen for patients with ade- ized ratio (INR), and beta-human chorionic gonado-
quate oxygenation [4]. tropin (HCG) for women of childbearing age. The only
Blood pressure (BP) measurements are vital and must required laboratory test prior to administration of IV
be obtained frequently, especially in the early manage- thrombolysis is CBG (fingerstick glucose) since it can be
ment of AIS. Hypotension is uncommon in AIS and may completed quickly to rule out hypoglycemia as a stroke
indicate recrudescence of symptoms of a previous stroke mimic [8].
Table 3  Intravenous antihypertensive agents used to lower blood pressure to attain alteplase eligibility

Labetalol
• Start with 10–20 mg IV bolus over 1–2 min; may repeat every 10 min. Onset of action 2–5 min, peak effect 5–15 min, and duration of action 16–18 h,
and dose dependent (e.g., longer effect with multiple doses)
• Consider doubling dose (i.e., 20 mg, 40 mg, 80 mg) to a maximum total dose of 300 mg, followed by a maintenance infusion (0.5–10 mg/min)
The importance of the maintenance infusion should not be underestimated or dismissed. If a bolus was required to lower the BP, then the BP should be
assumed to climb again as soon as the bolus wears off, potentially placing the patient in danger of ICH due to the uncontrolled BP. Start an infusion
if labetalol boluses successfully lower the BP. Accumulation of labetalol after multiple doses may lead to prolonged hypotension. If the patient is no
longer deemed a candidate for alteplase and permissive hypertension is being planned, then the infusion may be discontinued, provided the BP does
not rise above 220/120 mmHg
Hydralazine
• 10–20 mg IV every 4–6 h
• In hypertensive crisis 5–10 mg IV/IM initially, then 5–10 mg every 20–30 min PRN or 0.5–10 mg/h IV infusion. Dose is increased and decreased by
2 mg/h every 10 min
• Onset of action 5–20 min, duration 2–12 h and half-life 2–8 h
Nicardipine
• Begin with 5 mg/h IV infusion
• Titrate by 2.5 mg/h at 5–15-min intervals to a maximum total dose of 15 mg/h to achieve goal BP. Be prepared to lower the dose once target BP has
been reached
• Onset within minutes, half-life 2 h and duration of action 0.5–3 h
Clevidipine
• Begin with 1–2 mg/h IV infusion
• Double the dose every 90 s until BP goal is neared and then increase in smaller increments until desired BP goal is reached. Maximum dose is 32 mg/h
• Onset 2 min, half-life 1 min, and duration of action 5–15 min
Urapidil
• Bolus of 12.5–25 mg followed by continuous infusion at a rate of 5–40 mg/h
• Onset in 3–5 min and duration of action 4–6 min
Clonidine
• Initial oral dose of 0.1–0.2 mg followed by hourly doses of 0.05–0.1 mg until goal blood pressure is achieved
• Total dose of 0.3 mg
• Clonidine* Begin with intravenous infusion of 0.2 mcg/kg/min and not to exceed 0.5 mcg/kg/min. Not to exceed 0.15 mg per infusion
* Parenteral formulation in the USA only for epidural administration
Sodium nitroprusside
• 0.3–0.5 mcg/kg/min initially, increase by 0.5 mcg/kg/min every few minutes to achieve desired effect, maximum 10 mcg/kg/min, but recommend
maintaining < 2 mcg/kg/min to avoid toxicity
• Onset in < 2 min, duration 1–2 min, and half-life 2 min
BP blood pressure, ICH intracerebral hemorrhage

The safety of thrombolytic use in patients taking direct observational data [21]. If a patient is deemed a candi-
thrombin inhibitors or direct factor Xa inhibitors is not date for thrombolysis and there is no reason to suspect
firmly established. It may be prudent to check a throm- abnormal laboratory test results, thrombolytics should
bin time (TT), and/or ecarin clotting time (ECT), or be administered without waiting for these laboratory
chromogenic anti-Xa activity assays, respectively. While test values to prevent further delay [8]. If the patient’s
accurate cutoff points of these laboratory tests have not coagulation and platelet count results are abnormal
yet been determined, negative results may assist in iden- (INR > 1.7 or PT is abnormally elevated, platelet count
tifying the patient who is non-compliant with this class < 100,000 mm3), then thrombolytics should be discontin-
of medications, and therefore eligible for thromboly- ued [8].
sis. Many hospitals may not have these laboratory tests/
results available quickly within thrombolysis window. Imaging
Currently, the AHA does not provide recommendations With EMS prehospital notification of a potential stroke
on reversing oral anticoagulants with their antidotes patient, a doorway assessment by the clinician and
in order to give thrombolysis [3]. However, this may be simultaneous patient registration can facilitate rapid
considered on selected patients based on the preliminary patient transport to imaging. There should be a goal of
completing a head CT scan and/or MRI within 20  min Healthcare providers wishing to learn how to perform
of the patient’s arrival in at least 50% of patients who the NIHSS and receive free certification can find these
are candidates for thrombolysis and/or mechanical resources online through the American Stroke Associa-
thrombectomy [3]. CTA of the head and neck and CTP tion and the National Stroke Association.
should be completed when possible with this initial CT. The NIHSS score may also be used as a guideline to
These multimodal imaging studies should not delay predict a relative risk of ICH in patients who are given
administration of thrombolytics [3]. Chest X-ray is no thrombolytics, as given in Table 5 [26]. However, despite
longer routinely recommended during the acute phase of this escalating risk of hemorrhage, the benefits of throm-
the workup [8]. bolytic therapy must continually be weighed against the
risk for all eligible AIS patients.
Stroke Team Activation
If available, the stroke code system should be activated. Management
The acute stroke team should evaluate the patient
< 15 min of the patient entering the ED [8]. The composi- Intravenous Fluids
tion of the stroke team will vary between centers but usu- Patients presenting with AIS are typically hypo- or euv-
ally consists of one or more of the following: neurologist, olemic [3]. Hypovolemia should be corrected in the set-
ED physician, resident or APP, rapid response nurse who ting of AIS as it can worsen ischemic injury as a result
is specifically trained in recognition and acute manage- of impaired perfusion to brain tissue. Hypovolemia may
ment of AIS. Again, prehospital notification by EMS and exacerbate ischemic brain edema and increase stress
paging the stroke team can expedite patient assessment on the myocardium. Euvolemia is desirable in the acute
on arrival and in CT, thereby decreasing time to deter- stroke setting and most stroke patients should receive
mine thrombolytic candidacy. maintenance isotonic intravenous fluids in the form of
normal saline. Hypotonic and dextrose including flu-
NIHSS ids should be avoided. The utilization of plasma volume
The NIHSS is the preferred stroke severity rating scale expanders has not demonstrated benefit.
recommended as a standardized method for examiners
to reproducibly and quantifiably assess a patient’s stroke LKW < 3 h: IV thrombolysis
symptoms [22]. Scores range from 0 (no deficit) to 42 Alteplase is a thrombolytic medication and is the only
(Table 4). tissue plasminogen activator approved for the treatment
The NIHSS has some limitations, especially in scoring of acute stroke in the USA. When patients present < 3 h
brainstem strokes and estimating the severity of a right since their LKW time, eligibility for IV thrombolytic ther-
hemispheric stroke. In the 2007 AHA/ASA guidelines, apy should be assessed as well as ensuring no contraindi-
an NIHSS of 4 was a threshold to treat AIS with throm- cations exists (Table  6). One relative contraindication is
bolytics, but in the 2018 guidelines, a low score is not an “clearing neurological deficit.” However, some patients
absolute contraindication and potential risks should be will have symptom resolution without thrombolytics but
weighed against anticipated benefits. While the NIHSS others may improve somewhat from a severe stroke yet
helps to standardize the examination, a better tool to fail to clear further. If a patient has plateaued or still has
determine whether or not to recommend thrombolysis in significant stroke symptoms without contraindication,
patients with a low NIHSS is to determine whether the treatment with thrombolysis should proceed as it would
symptoms are disabling to the patient. In mild strokes, otherwise. Also, some patients will present with stutter-
asking the patients directly if their symptoms are disa- ing symptoms. If symptoms completely resolve, clini-
bling or hindering them will often make the decision cians should reset the clock to start a new thrombolysis
process easy. It is notable that in a large 2011 study of candidacy window; if there are still symptoms—however
patients deemed “too good to treat,” 28% could not be mild—the time of onset remains unchanged. Patients
discharged home and another 28% could not walk inde- with stuttering symptoms tend to be high risk for extend-
pendently at discharge [23]. Other studies in patients ing their vascular occlusions. Be aware that some patients
with minor strokes have demonstrated lack of signifi- will have pressure-dependent lesions and lowering of
cant difference in outcomes and increased risk of symp- blood pressure may actually exacerbate their symptoms;
tomatic hemorrhage from thrombolytic use [24, 25]. conversely, allowing their blood pressure to rise permis-
Clinicians should carefully consider, and document, the sively up to accepted thresholds of 220/120 mmHg (when
individual patient’s relative risks, potential benefit, and not given thrombolytics) may improve their deficits.
premorbid status when evaluating a patient for treatment It is important to recognize that the majority of expe-
with thrombolysis. rience with the administration of thrombolysis over the
Table 4  National Institutes of Health Stroke Scale (NIHSS) [3]
Category Scale definition Score

1a. Level of consciousness 0 = Alert

1 = Not alert, arousable by minor stimulation
2 = Not alert, requires repeated stimulation
3 = Unresponsive, responds only with reflex
1b. Level of consciousness questions 0 = Answers both questions correctly
1 = Answers one question correctly
2 = Answers neither question correctly
1c. Level of consciousness commands 0 = Performs both tasks correctly
1 = Performs one task correctly
2 = Performs neither tasks correctly
2. Best gaze 0 = Normal
1 = Partial gaze palsy
2 = Forced deviation
3. Visual 0 = No visual loss
1 = Partial hemianopia
2 = Complete hemianopia
3 = Bilateral hemianopia
4. Facial palsy 0 = Normal
1 = Minor paralysis
2 = Partial paralysis
3 = Complete paralysis of one or both sides
5. Motor arm
5a. Left arm 0 = No drift
1 = Drift
2 = Some effort against gravity
3 = No effort against gravity
4 = No movement
5b. Right arm 0 = No drift
1 = Drift
2 = Some effort against gravity
3 = No effort against gravity
4 = No movement
6. Motor leg
6a. Left leg 0 = No drift
1 = Drift
2 = Some effort against gravity
3 = No effort against gravity
4 = No movement
6b. Right leg 0 = No drift
2 = Some effort against gravity
3 = No effort against gravity
4 = No movement
7. Limb ataxia 0 = Absent
1 = Present in one limb
2 = Present in two limbs
8. Sensory 0 = Normal; no sensory loss
1 = Mild to moderate sensory loss
2 = Severe to total sensory loss
9. Best Language 0 = No aphasia; normal
1 = Mild to moderate aphasia
2 = Severe aphasia
3 = Mute, global aphasia
10. Dysarthria 0 = Normal
1 = Mild to moderate dysarthria
2 = Severe dysarthria
11. Extinction and inattention 0 = No abnormality
1 = Visual, tactile, auditory, spatial or personal inattention
2 = Profound hemi-inattention or extinction
Table 5  Risk of  intracranial hemorrhage with  IV alteplase Table 
7 Additional inclusions to  IV alteplase use
treatment [30] between 3 and 4.5 h [3, 28]
NIHSS score Risk of intracra‑ Meet all criteria of < 3 h since onset of stroke
nial hemorrhage
(%) For patients taking warfarin and with an INR ≤ 1.7
INR international normalized ratio
0–10 2–3
11–20 4–5
> 20 17
can bring back old, subclinical stroke symptoms and,
NIHSS National Institutes of Health Stroke Scale
once corrected, these stroke-like symptoms may resolve.

past 20  years has utilized treatment algorithms consist- LKW Between 3 and 4.5 h: IV Thrombolysis
ent with the AHA/ASA guidelines. Some contraindica- In the USA, the food and drug administration (FDA) has
tions to thrombolytics use are time (duration from first not yet approved thrombolysis use between 3 and 4.5 h,
symptom > 4.5  h), recent surgery, current bleeding at a though it has been approved in Europe and Canada.
non-compressible site, as well as large area of cerebral However, thrombolysis use in this timeframe has been
infarction that is already apparent as low density on the endorsed by the AHA/ASA and is widely used in the
initial brain CT or MRI study [> 1/3 of the middle cer- USA [8, 28].
ebral artery (MCA) territory]. The inclusion criteria are similar to those of onset < 3 h
Patients with major neurological deficits have a high (discussed above), but are modified as noted in Table 7.
risk of poor outcome, regardless of whether or not throm-
bolysis is administered. In these cases, realistic expecta- Patient is an IV Thrombolysis Candidate
tions and risks associated with either choice should be Once a patient is deemed a candidate for IV thrombolyt-
discussed with the patient’s family members, and a joint ics, a minimum of two IVs must be placed. It is impera-
decision should be made. While a glucose level greater tive to obtain the most accurate dosing weight as possible;
than 400 mg/dL/22.2 mmol/L is not a contraindication, it however, in the event this cannot be done, two experi-
should be noted that high glucose may be a stroke mimic, enced healthcare providers should agree upon a dos-
can be associated with worse outcome, and may increase ing weight to be utilized. Alteplase is dosed at 0.9  mg/
the risk of intracranial hemorrhage [27]. Similarly, the kg based on actual body weight and should be mixed by
presence of fever should prompt a reconsideration of the swirling (rather than shaking), with the total dose not to
diagnosis. For example, a simple urinary tract infection exceed 90  mg. The initial 10% of the total alteplase dose

Table 6  Eligibility and  absolute contraindications for  use of  IV alteplase (AHA/ASA 2018 guidelines)—abbreviated ver-
sion
Eligibility

Ischemic stroke symptoms causing measurable neurological deficit. These may range from mild but disabling to severe stroke symptoms
Onset less than 3 h from start of symptoms
Patient is ≥ 18 years of age
Absolute exclusion criteria
 Major head trauma, ischemic stroke, intracranial/spinal surgery in the previous 3 months
 History of intracerebral hemorrhage or intracranial neoplasm
 Signs and symptoms suggestive of subarachnoid hemorrhage, infective endocarditis or aortic arch dissection
 GI malignancy or recent bleeding within 21 days
 Taking direct thrombin inhibitors or direct factor Xa inhibitors unless APTT, INR, platelet count, ecarin clotting time, thrombin time, or direct factor Xa
activity assays are normal or has not received a dose for > 48 h (with normal renal function)
 CT shows severe hypoattenuation, hypodensity > 1/3 of cerebral hemisphere or intracerebral hemorrhage
Additional recommendations
 Extended 3–4.5 h is safe in patients > 80 years, patients on warfarin with INR ≤ 1.7, prior stroke with diabetes
 IV alteplase is reasonable in patients with early improvement but moderately disabled, seizure at symptom onset if deficits are from stroke, lumbar
dural puncture in previous 7 days, major surgery or trauma in previous 14 days, extracranial cervical dissections, unruptured intracranial aneurysm,
small number of cerebral microbleeds on MRI, extra-axial intracranial neoplasm, acute or recent MI in the past 3 months, acute pericarditis, diabetic
retinopathy, sickle cell disease, angiographic procedural stroke, pregnancy, illicit drug use and stroke mimics
APTT activated partial thromboplastin time, CT computed tomography, INR international normalized ratio, MI myocardial infarction, MRI magnetic resonance imaging
is given by bolus over 1  min, and then the remainder is ••  Vital signs every 15  min (neurological assessment
infused over 1  h. As alteplase is dispensed in 2–100  mg for signs of increased intracranial pressure). Assess
bottles, excess alteplase should be withdrawn from the vial GCS/pupil response. Treat BP and use noninvasive
and discarded to avoid accidental infusion of the excess. interventions to lower intracranial pressure (ICP)
A 100-ml bag of saline should be administered after the (raise the head of bed, neck midline) [30].
1-h infusion to flush the IV line to ensure that the entire ••  Supportive therapy, including management of BP,
dose is administered. This flush should be run at the same ICP, cerebral perfusion pressure (CPP), temperature,
rate as the infusion to avoid a terminal alteplase bolus. In and glucose should be performed.
the case of patient transfer after initiation of bolus or infu- ••  Cryoprecipitate (contains fibrinogen): 10 units
sion, conscious efforts should be made to ensure the tub- infused over 10–30  min; administer additional dose
ing or flush is complete prior to disconnecting to prevent for fibrinogen level < 150  mg/dl. Due to its lack of
incomplete dose administration. Use of extension tubing availability in certain countries, fibrinogen concen-
or an IV pump from transporting facility/air or ground trate has been used to replenish the fibrinogen lev-
carrier can assist in the timeliness of transfer without els [32]. The initial dose is 2 gm of IV fibrinogen fol-
losing part of the administered drug. Alternative dosing lowed by further dosing based on fibrinogen levels.
strategies utilizing lower doses has been evaluated in the In addition, prothrombin complex concentrate (25–
literature; however, currently these dosing strategies are 50 U/kg) and fresh frozen plasma (12 ml/kg) may be
not endorsed by the AHA/ASA guidelines and should not as an adjunctive therapy to normalize the INR.
be routinely implemented [3, 29]. ••  Antifibrinolytics such as tranexamic acid 1000  mg
During the hospital admission or transfer period, there (10–15  mg/kg) IV or ε-aminocaproic acid 4–5  g IV
should be continued observation for complications of over 1  h, followed by 1  g IV until bleeding is con-
thrombolytics including airway obstruction due to angi- trolled. These competitively bind to plasminogen and
oedema (consider rapid intubation), hemorrhage (stop block its conversion to plasmin, thereby inhibiting
alteplase), and sudden deterioration in mental status. fibrin degradation. While it has a theoretical advan-
Guidelines require that the BP and neurological assess- tage over cryoprecipitate, in terms of cost, shorter
ment of a patient be checked every 15  min for the first administration time (as it does not require thawing),
2 h after starting alteplase, then every 30 min for the next there is little evidence of its efficacy.
6 h, and then hourly for the next 16 h [3, 30]. ••  One bag of single donor platelets or 6–8 bags of ran-
While the half-life of alteplase is approximately 5 min, dom donor platelets may also be transfused.
and only 20% of the medication is still present and active ••  Consult neurosurgery. If a neurosurgeon is not avail-
at 10 min after completion of the infusion, PT and acti- able, begin the process of transferring the patient to
vated partial thromboplastin time (APTT) are prolonged a facility with neurosurgical capability once CT scan
and fibrinogen levels are decreased for 24 h or more. An results are available
acute onset of headache, nausea, vomiting, worsening
neurological examination during or following alteplase For small, asymptomatic, hemorrhagic conversion, con-
administration may signal an intracranial hemorrhage servative medical management may be considered after
[31]. Intracranial bleeds following IV alteplase carry a weighing the risks and benefits of reversal agents.
50% or greater mortality rate. This is often accompa-
nied by a marked rise in blood pressure (BP); however, Tenecteplase
a marked rise or fall in BP alone may signal an ICH. In Tenecteplase (TNKase) is a thrombolytic agent with
these cases, the following steps should be immediately high fibrin specificity. In a phase 3, randomized, open-
taken. label trial, tenecteplase was not superior to alteplase
in ischemic stroke patients when administered within
Management of Hemorrhage Following Alteplase 4.5  h of symptom onset [33]. However, administration
For symptomatic intracranial bleeding within 24 h of IV of tenecteplase (0.25  mg/kg with maximum of 25  mg)
alteplase within 4.5  h in patients that underwent thrombectomy
was associated with a higher rate of reperfusion and
••  Stop alteplase infusion better functional outcome when compared to alteplase
••  Obtain a non-contrast head CT scan STAT​ [34]. Further studies with tenecteplase are ongoing in
••  Obtain CBC, PT, PTT, INR, fibrinogen level, type the USA. Currently, the AHA/ASA has recommended
and cross-match IV bolus of tenecteplase 0.4  mg/kg (maximum 40  mg)
as an alternative to alteplase in patients with minor
Table 8  Recommendations for endovascular intervention

Patients eligible for intravenous alteplase should receive intravenous alteplase even if endovascular treatments are being considered
Patients should receive endovascular therapy with a stent retriever if they meet all the following criteria:
• Prestroke mRS score 0–1
• Acute ischemic stroke receiving intravenous alteplase within 4.5 h of onset according to guidelines from professional medical societies
• Causative occlusion of the internal carotid artery or proximal MCA (M1)
• Age ≥ 18 years (note: there is no upper age limit)
•  NIHSS score of ≥ 6
• ASPECTS of ≥ 6 and
• Treatment can be initiated (groin puncture) within 6 h of symptom onset based on CTA only
• Treatment in the 6–24-h time window is based on the presence of target mismatch profile on CTP/MR perfusion imaging
As with intravenous alteplase, reduced time from symptom onset to reperfusion with endovascular therapies is highly associated with better clinical
outcomes.
In carefully selected patients with anterior circulation occlusion who have contraindications to intravenous alteplase, endovascular therapy with stent
retrievers completed within 6 h of stroke onset is reasonable
Although the benefits are uncertain, use of endovascular therapy with stent retrievers may be reasonable for carefully selected patients with acute
ischemic stroke in whom treatment can be initiated (groin puncture) within 6 h of symptom onset and who have causative occlusion of the M2 or M3
portion of the MCAs, anterior cerebral arteries, vertebral arteries, basilar artery, or posterior cerebral arteries
Endovascular therapy with stent retrievers may be reasonable for some patients < 18 years of age with acute ischemic stroke who have demonstrated
large vessel occlusion in whom treatment can be initiated (groin puncture) within 6 h of symptom onset, but the benefits are not established in this
age group
Observing patients after intravenous alteplase to assess for clinical response before pursuing endovascular therapy is not required to achieve beneficial
outcomes and is not recommended
Endovascular therapy with stent retrievers is recommended over intra-arterial fibrinolysis as first-line therapy
ASPECTS Alberta Stroke Early CT Score, MCA middle cerebral artery, NIHSS National Institutes of Health Stroke Scale, CTA​CT angiogram, CTP CT perfusion, MR magnetic
resonance

neurological impairment and no arterial occlusion [3, clot within the vessel) on non-contrast CT, but this sign
33]. Tenecteplase (IV thrombolytic) is not FDA-approved is insensitive. CTA or MRA are more diagnostic, as is
for treating AIS in the USA, whereas in some countries, conventional angiography. It is prudent to contact the
tenecteplase is approved and is the thrombolytic that is neurointerventional physician on call, if one is available.
more commonly used. ENLS encourages providers to fol- If the treating hospital does not have this capability, rapid
low their national stroke guidelines for recommendations transfer to a comprehensive stroke center (CSC) is rec-
on tenecteplase use. ommended. If the patient is suspected to have an LVO,
transfer to a CSC should not be delayed; these patients
LKW Between 0 and 6 h: Endovascular Treatment can deteriorate quickly and a delay in transfer could limit
If the patient has an LVO—e.g., proximal (M1) MCA, capability of potential endovascular intervention. Some
intracranial internal carotid artery (ICA), basilar or ver- hospitals use CTA and/or CTP or MRI/MRA techniques
tebral artery—or suspected LVO and the patient is within to select appropriate patients referred for endovascular
6  h of LKW time, mechanical thrombectomy treatment intervention; there is no standard for these practices in
should be considered. If the patient is a candidate for IV the < 6-h time window. Sites performing multimodal CT
thrombolytics, it should be administered expeditiously, imaging should be able to expeditiously perform a high-
regardless of endovascular procedure candidacy. Previ- quality study and have the capacity to transfer the patient
ously, intra-arterial (IA) thrombolysis was considered to to a CSC.
be an option; however, alteplase has no FDA recommen- Exclusions for  mechanical thrombectomy include the
dation for IA use and is no longer recommended as iso- absence of an LVO on CTA or MRA, or large area of
lated therapy [35, 36]. Several 2015 randomized trials of infarction already present in the brain imaging study.
thrombectomy in acute LVO stroke have shown marked Many providers use an ASPECTS score of greater than 6
clinical efficacy and reduction in mortality [37–40]. to proceed with intervention [9]. Detailed information on
Patients with distal occlusion, e.g., M2, M3, anterior cer- training and scoring of ASPECTS score can be found on
ebral arteries, posterior cerebral arteries, and vertebral or www.aspectinstroke.com. Others use additional MRI and
basilar artery, have uncertain benefits. MRA. Table 8 summarizes the AHA/ASA recommenda-
Patients with a high NIHSS will often have an LVO. tions for endovascular intervention (Fig. 3).
LVO can be confirmed by seeing a hyper-dense sign (i.e.,
 Fig. 3  ASPECTS (Alberta Stroke Early CT Score) score is a ten-point quantitative score used to assess early ischemic changes in anterior circulation
strokes on non-contrast CT head. Each area of gray white loss constitutes 1 deduction point from a total score of 10

LKW Between 6 and 24 h: Endovascular Treatment The DAWN trial used a clinical-imaging mismatch to
Based on the results of the DAWN and DEFUSE 3 tri- select patients with anterior circulation strokes due to
als, it is recommended that in patients presenting with LVO to select patients for mechanical thrombectomy
an AIS within 6–24  h of LKW time who have an LVO between 6 and 24 h of LKW time [19]. It demonstrated an
in the anterior circulation, obtaining a CTP, DWI— overall benefit in functional outcome at 90  days follow-
MRI + MRI perfusion is recommended to aid in selection ing endovascular therapy compared to the control group
of patients for mechanical thrombectomy who meet the (mRS score 0–2, 49% vs. 13%, adjusted difference, 33%,
eligibility criteria [19, 20]. Both these trials incorporated 95% CI 24–44, with a probability of superiority, > 0.999).
CTP or MRI diffusion and perfusion scans that used the An area of intense investigation is trying to determine
RAPID software (iSchemaView), an automated image the ideal destination for patients in the field with sus-
processing system to calculate the volume of ischemic pected LVO. Various rapid assessment tools are being
core (or infarct volume) and penumbral tissue. The size trialed to help EMS best decide which patient may have
of penumbral tissue was estimated from the volume of an LVO. Based on patient location, and distances and
tissue for which there was delayed arrival of an injected direction of local primary stroke centers (PSCs) and
tracer agent (time to maximum of the residual function) regional CSC, work is being done to try to determine
exceeding 6 s (Fig. 4). which patients should travel a short distance further to
The DEFUSE 3 trial randomized patients with signs a CSC versus going a shorter distance to a PSC to initi-
and symptoms of anterior circulation stroke with LVO, ate thrombolytics and then be transferred out. Unless
NIHSS ≥ 6 with a target diffusion–perfusion mismatch there are compelling mitigating circumstances, it is
profile to endovascular therapy or medical management recommended by AHA/ASA that EMS not bypass the
[20]. The target mismatch profile was defined as patients closest facility to go to the higher-level facility if such a
with ischemic core volume of < 70  ml, and a mismatch diversion would add 15–20  min to the transport time.
ratio of > 1.8 or ≥ 15 ml (ratio of ischemic penumbral tis- These recommendations predate the most recent data
sue volume to infarct volume). This trial showed a benefit demonstrating the value of endovascular intervention
in functional outcome in favor of the endovascular ther- in selected patients. When there are several PSCs and
apy (modified Rankin scale 0–2, 44.6% versus 16.7%; RR CSCs with roughly equal distances for transport, AHA/
2.67; 95% CI 1.60–4.48; P < 0.0001). ASA generally recommends transportation to the highest
 Fig. 4  a Axial view of CTA brain showing proximal right M1 occlusion. b CT perfusion showing a disproportionately large area of hypoperfu-
sion (shown in green) as compared with the size of early infarction–ischemic core–perfusion mismatch

Table 9  Sample acute stroke admission orders

□ Neuro checks every 15 min for 2 h, then every 30 min for 6 h, then hourly
□ Supplemental oxygen to keep ­O2 saturation  ≥ 94%
□ BP check every 15 min for 2 h, then every 30 min for 6 h, then every hour for 16 h (if received alteplase)
□ Keep BP after alteplase treatment < 180/105 mmHg (note: this is lower than pretreatment values); if no alteplase given, keep BP < 220/120 mmHg
□ Bedside swallow test (30 mL water PO) before anything else PO
BP blood pressure, PO per oral

level facility [4]. Ground versus helicopter transport fac- Hospital Admission or Transfer
tors into this as well, especially when the closest PSC is in Assuming there are no complications of alteplase or
the opposite direction of the CSC. Prearranged transfer endovascular therapy, Table  9 shows the orders that
agreements should be established to ensure rapid transfer should be considered while waiting for the patient to be
to the highest level of care when necessary. admitted. Note this sample is based on 2018 AHA/ASA
guidelines.
Additional admission orders must address glucose, vol-
ume status, body temperature, and catheters:
 ••  Keep glucose 140–180  mg/dL/7.8–10.0  mmol/L; administration time including time of the start of the
consider insulin drip if the blood glucose is persis- bolus, infusion start time, and when the infusion ended.
tently > 200  mg/dL/11.1  mmol/L or the patient is In the first 24 h of care, a nursing handoff during transi-
known to have insulin-dependent diabetes mellitus. tions of care (emergency room (ER) to intensive care unit
Hyperglycemia is associated with worsen outcomes (ICU), ER to endovascular suite, endovascular suite to
and increased risk of ICH following AIS. ICU, etc.) should include bedside report with both nurses
••  Administer IV fluids, preferably isotonic saline, at completing the neurological assessment on the patient
1.5 ml/kg/h initially, with a goal of euvolemia. together. Any differences in scoring should be identified
••  Continue telemetry/bedside cardiac monitoring if it is a true change, and if a true change has occurred,
principally to detect paroxysmal atrial fibrillation and clinician notification should occur for additional orders.
should continue for at least 72 h after admission. Any decline in neurological assessment should prompt
••  Treat fever sources with appropriate antibiotics or an expedited CT to rule out hemorrhagic transformation.
therapies while preventing fever with antipyretics. For those patients that do not receive thrombolytics
While occasionally used in post-cardiac arrest situ- but underwent mechanical thrombectomy, frequent neu-
ations as a neuroprotective maneuver, hypothermia rological status checks should be done to quickly identify
has not been sufficiently studied to recommend at changes from potential re-occlusion, hemorrhagic trans-
present. The presence of fever should prompt an formation, and other causes. The groin site of catheteri-
investigation of the cause of the fever. zation should also be monitored for bleeding.
••  If thrombolytic was administered, avoid indwelling
urinary catheter, nasogastric tubes, and IA catheters Nursing pearls
for 4  h, and do not give anticoagulant/antiplatelet • If patient has acute neurological deficit, check fingerstick glucose and
therapy for 24 h. Urinary catheters should in general activate the stroke team
be avoided unless absolutely needed. • CT scan of head should not be delayed for laboratory work
••  While elevation of the head of bed is recommended • Obtain the actual weight of the patient, consider use of a bed scale
for decreasing the risk of aspiration pneumonia, it • Obtain an 18-gauge IV access for perfusion imaging, obtain second IV if
was not found to make any difference in disability the patient will be receiving thrombolytics or going to interventional
radiology for thrombectomy.
outcome of the stroke injury [41].
• IV tPA is mixed with swirling not shaking
••  Patients should be nil per oral (NPO) until evaluated
•  IV tPA dose should be double-checked with second clinician (RN,
for swallowing difficulties by a bedside RN evaluation PharmD, APP, MD) & BP and neurological status checked within 15 min
or a speech therapist. prior to administration
• Bolus dose, infusion dose, wasted IV tPA, and follow-up flush post IV-tPA
should be documented
Nursing Considerations • BP goal prior to IV tPA administration is < 185/110 mmHg and after
IV tPA administration is < 180/105 mmHg for 24 h
Stroke patients presenting to triage often present with
• Patients not receiving IV tPA may be allowed to have permissively higher
varying symptoms and sudden onset of symptoms which blood pressure up to 220/110 mmHg
should trigger stroke protocol activations. Using preap- • Notify the provider immediately with a sudden decline in neurological
proved assessment tools can help with organizing vital status and/or acute hypertension or angioedema
time stamps, key neurological assessments, and goals of
care during the acute phase of AIS management. Front-
line nursing education is vital to ensure key time-stamp
goals are achieved by intimate knowledge of alert proto- Pediatric Stroke
cols and team roles. While not as common as in older adults, pediatric stroke
While timely administration of IV thrombolytics is cru- occurs in 1.6–13/100,000 children each year, and it car-
cial, a timeout within the 15 min prior to administration ries an associated 14% risk of mortality, in addition to
of medication is considered best practice. A timeout is functional and cognitive and psychosocial sequelae over
beneficial to ensure patient safety, establish clear goals of the lifetime of the patients [42–44]. While select popula-
care within the stroke team, and identify key personnel tions, such as children under 1 year of age and children
if issues should arise. Once IV thrombolytics administra- with sickle cell disease (SCD) or congenital heart disease,
tion has been initiated, nursing should ensure accurate have a higher incidence of AIS, the most important risk
factor is the presence of a cerebral arteriopathy [45–48].
Challenges in identifying stroke within the pediatric Table 10  ABCD2 score for TIA [64, 65]
population include at times different presentation than ABCD2 Score Points
adults and broad differential diagnoses. Pediatric stroke
often presents with seizures, particularly within the Age > 60 years 1
younger pediatric population [49]. Headache, and other BP ≥ 140/90 mmHg at initial evaluation 1
diffuse, non-localizing signs may also be part of the pre- Clinical features of the TIA
senting symptoms. Additionally, other diagnoses, such as Speech disturbance without weakness 1
migraine, may be equally or even more likely in children Unilateral weakness 2
presenting with an acute neurologic change [47]. Imag- Duration of symptoms
ing, particularly with MRI, is crucial for establishing the 10–59 min 1
diagnosis [50]. The Pediatric NIHSS (PedNIHSS), similar > 60 min 2
to the adult NIHSS, is a validated, age-appropriate tool Diabetes mellitus in patient’s history 1
for quantifying neurologic deficits in pediatric stroke 2
Add all of the points for the total ­ABCD score (0–7)
and, similar to young adult stroke, is the most important TIA transient ischemic attack
predictor of outcomes [43, 51, 52].
Despite its lack of approval for children under 18 years
of age, there are several case reports of alteplase use Safety and efficacy of intravenous alteplase and endovas-
in pediatric ischemic stroke cases in the literature. A cular interventions in this population is not established
recent multicenter trial to examine safety and efficacy of in a randomized controlled trial. However, a case control
alteplase in children 2–18 years old was closed early due retrospective analysis from the Get With the Guidelines-
to insufficient enrollment [53]. While this study high- Stroke Registry of adults with SCD compared with an
lights the challenge of confirming a diagnosis of stroke NIHSS- and BP-matched control population demon-
in children within 4.5  h of symptom onset, analysis of strated no difference in symptomatic ICH or outcome
data from the Kids Inpatient Database from 1998 to 2009 measures after treatment with alteplase [62]. This led to
demonstrated an increase in the number of pediatric their recommendation and a new recommendation in
patients treated with alteplase, particularly among the the AHA/ASA 2018 Stroke management guidelines that
adolescent population [54]. There are several case reports adults with SCD who otherwise meet criteria for stroke
and series of children < 18 years old that underwent end- thrombolysis with alteplase should receive alteplase in
ovascular treatment for LVO documenting high rates of addition to the other acute therapies recommended for
recanalization and favorable outcomes; however, there stroke in SCD [3].
are no randomized trials [9, 55–57]. While individual
physicians may continue to offer thrombolysis therapy TIA
with appropriate parental informed consent, one should The diagnosis of TIA is based on the new onset of focal
be careful to apply similar strict inclusion and exclusion neurological symptoms and signs that are explainable
safety criteria as used in adults [58]. Regardless of age or by a vascular disease (e.g., arterial occlusion of a single
antithrombotic treatment, similar neuroprotective strate- or group of arteries adequately explain the patient’s signs
gies should be employed for pediatric stroke as described and symptoms), and the resolution of these signs and
above for adult stroke. Such strategies include avoiding symptoms within 24  h (most TIAs resolve in a much
fever and maintaining normoglycemia, euvolemia and shorter period of time).
adequate BP (50–90%tile for age and height), as retro- However, up to one-third of TIAs have demon-
spective analyses have shown that hyperglycemia and strable injury on MRI [63]. These cases are now clas-
hypertension (> 95%tile) have been associated with poor sified as stroke. Despite evidence of tissue injury, it is
neurological outcomes [59, 60]. unlikely that emergency reperfusion therapy should be
There are currently no guidelines recommenda- attempted, since all symptoms have resolved.
tions regarding use of alteplase in pediatric patients TIAs present a conundrum as there clearly was an
with stroke due to SCD [3, 58]. Prevention by transfus- event and the patient is at some risk of a recurrence.
ing selected children with low hemoglobin levels peri- There are several tools that may help provide guidance
odically decreased the incidence of stroke from 10 to assessing the risk of recurrence or outright stroke at dif-
1% in the STOP trial [61]. Current standard therapy ferent time intervals and each has its limitations. One
for sickle cell patients with acute stroke includes opti- must assess the patient compliance, available resources in
mal hydration, blood exchange transfusion (maintain- one’s practice environment and make a decision with the
ing Hgb ≤ 10  g/dL/6.21  mmol/L to avoid hyperviscosity patient and family for the best disposition and follow-up
syndrome), and correction of hypoxia and hypotension.
Table 11  Percent risk of stroke following TIA with various tin 20–40  mg, pravastatin 40–80  mg) in patients
­ABCD2 scores [64, 65] > 75 years old [73].
Total risk Score 2 Day 7 Day 90 Day
If electrocardiogram (ECG) or rhythm strip shows
Low 0–3 1.0 1.2 3.1 atrial fibrillation, consider starting anticoagulation (oral
Moderate 4–5 4.1 5.9 9.8 anticoagulant or low molecular weight heparin) or ASA;
High 6–7 8.1 12 18 calculate CHADS2 or CHA2DS2-VASc, and HAS-BLED,
TIA transient ischemic attack scores to help guide long-term therapy [74, 75]. In these
cases, referral to a vascular neurologist or cardiologist is
plan. The ­ABCD2 score is commonly used and is pre- appropriate.
sented in the following section (Table 10).
High‑Risk TIA
For patients with higher-risk TIAs (­ABCD2 scores > 3),
ABCD2 Score hospital admission is advisable. Permissive hyperten-
The ­ABCD2 score is an ordinal scale that provides risk sion is encouraged (not to exceed 220/120  mmHg),
prediction of subsequent stroke following a TIA [64, 65]. and BP should be gradually lowered over 24–48  h. In a
While limitations exist, it is useful at stratifying risk of high-risk TIA ­(ABCD2 score ≥ 4), the CHANCE trial
stroke to some degree [66–68]. Table  11 demonstrates demonstrated that dual antiplatelet therapy using a com-
how to calculate this score. bination of clopidogrel (initial dose of 300  mg followed
Based on this risk stratification, some physicians by 75  mg/day) and aspirin 81  mg/day for 21  days fol-
choose to admit high-risk patients and discharge those at lowed by clopidogrel 75 mg/day for 90 days was superior
low-risk [64, 69]. There is controversy regarding admis- to aspirin alone in reducing the risk of stroke [71]. Simi-
sion of moderate-risk patients, and this decision follows larly, the POINT trial from USA showed that combined
local practices. use of clopidogrel at a loading dose of 600 mg once fol-
lowed by 75 mg/day for 90 days plus aspirin 50–325 mg/
Low‑Risk TIA day for first 21 days was superior to aspirin 50–325 mg/
For low-risk patients (­ABCD2 scores 0–3), an outpatient day for 90  days [72]. The SAMMPRIS trial showed that
workup in 1–2  days following score calculation may be in patients with TIA from stenosis of a major intracra-
most appropriate. Alternately, observation or admis- nial artery (70–99%), medical management with aspirin
sion may be an option. In either case, stroke risk can be 325  mg/day and clopidogrel 75  mg/day with aggressive
decreased by rapid implementation of the following regi- medical management of primary risk factors was supe-
men [70]: rior to combined medical therapy and intracranial stent-
ing group [76].
••  Begin an antithrombotic agent (ASA 81–300  mg/
day, clopidogrel 75 mg/day, or ASA 25 mg/extended
release dipyridamole 200 mg twice daily) [71, 72] Carotid Disease
••  Perform carotid imaging: carotid ultrasound, CTA, As part of emergent evaluation of patients with TIA or
or MRA. ischemic stroke, gathering information of extracranial
••  Consider transthoracic echocardiography; if bilateral and intracranial vasculature using noninvasive imag-
infarcts are present on CT or there is high suspicion ing like CTA or MRA of the head and neck is typi-
of cardiac embolic source, and transthoracic echo cally performed as part of the standard acute stroke
is normal, obtain transesophageal echocardiograph workup. Patients with ischemic stroke or TIA from
(TEE). extracranial carotid or vertebral artery dissection and
••  Consider 30-day ambulatory cardiac monitor to administration of antiplatelet or anticoagulation medi-
detect intermittent atrial fibrillation (cryptogenic cation within 24–48  h are recommended [3]. Recent
A-fib). This should be strongly considered if the data have demonstrated lack of significant difference
workup shows no other etiology for cause of stroke between antiplatelet and anticoagulation in patients
or TIA. with extracranial carotid and vertebral artery dissec-
••  Encourage smoking cessation. tion [77]. For patients with ischemic stroke or TIA
••  Initiate high-intensity statin (atorvastatin 40–80 mg/ from extracranial carotid or vertebral artery dissection
day or rosuvastatin 20–40  mg or equivalent). who have recurrent ischemic events despite medical
Consider moderate intensity statins (atorvasta- therapy, endovascular therapy or surgical treatment
tin 10–20  mg, rosuvastatin 5–10  mg, simvasta- may be considered [78].
Table 12  Ischemic stroke communication regarding assessment and referral
Communication

□ Age
□ Airway status
□ Last known well (LKW) time
□ NIHSS
□ Coagulation parameters—PT, PTT, INR
□ CT—dense MCA sign, MCA dot sign, dense basilar sign, ASPECTS score, early ischemic changes
□ CTA/MRA—large vessel occlusion (ICA, M1, M2, basilar, PCA)
□ CTP—volume of core and penumbra, matched or mismatched perfusion
□ Thrombolytic administration—yes (initiation, completion time); no (reason)
□ Endovascular intervention (time to groin puncture, recanalization, TICI score)
□ Target BP
Sample sign-off narrative
Prehospital to ER: “I am signing out a 62-year-old male with known hypertension and atrial fibrillation who is not on anticoagulation”
“He was found down on the floor at 7:10 am by his wife. He was last seen normal at 10 pm last night. He is aphasic with right-sided weakness, GCS of
11, HR of 130/min and BP of 200/110 mmHg. IV Metoprolol 5 mg given and his follow-up HR was 94/min and BP was 182/90 mmHg”
ER to ICU: “Upon arrival to the ER at 9:10 am his NIHSS was 21—global aphasia, left gaze preference, right hemiplegia and neglect”
“CT completed at 9:26 am showed a left dense MCA sign. CTA showed a left M1 occlusion. CTP showed a core of 38 ml, penumbra of 140 ml, mismatch
volume 102 ml, mismatch ratio 3.7”
“He was out of the IV tPA window. Endovascular team was notified at 9:38 am”
“He was taken to the cath laboratory at 9:50 am. His HR was 106/min and BP was 190/106 mmHg. Groin puncture was attained at 10:06 am. TICI3 revas-
cularization was achieved. He had started moving his right arm and leg few minutes after the procedure”
“His target post-procedural BP should be < 140/80 mmHg.” MRI brain is pending”
ASPECTS Alberta Stroke Early CT Score, BP blood pressure, CT computed tomography, CTA​CT angiogram, CTP CT perfusion, ER emergency room, GCS Glasgow coma
score, HR heart rate, ICA internal carotid artery, ICU intensive care unit, INR international normalized ratio, LKW last known well, MCA middle cerebral artery, MRA
magnetic resonance angiogram, MRI magnetic resonance imaging, NIHSS National Institutes of Health Stroke Scale, PCA posterior cerebral artery, PT prothrombin
time, PTT partial thromboplastin time, TICI thrombolysis in cerebral infarction

Revascularization for secondary prevention in patients ••  Far more lawsuits have been filed for failure to offer
with minor, non-disabling stroke and symptomatic thrombolytic treatment, than for bleeding complica-
carotid stenosis > 70% is performed between 48  h and tions arising from thrombolytic treatment [81, 82].
7  days of the event if there is no contraindication for ••  For acute stroke patients meeting guidelines for
early revascularization [3]. The usefulness of emer- thrombolytic therapy who are unable to consent for
gent or urgent carotid endarterectomy (CEA) or carotid themselves and have no family to consent for them,
artery stenting (CAS) in patients with small core and the treating physician should not delay treatment to
large territory at risk due to inadequate flow from critical find a surrogate to give permission for treatment.
carotid stenosis or occlusion in acute stroke is not well ••  Written/signed consent for administering throm-
established [3]. Recent data have demonstrated safety of bolytics is not necessary. The consenting conversa-
emergent CAS of extracranial carotid stenosis and CEA tion, however, should be documented in the medical
in patients with tandem lesions, but this will need to be record.
confirmed by randomized trials [79, 80]. ••  If a patient is not being offered thrombolytic ther-
apy, there should be clear communication with the
Medical–Legal Considerations patient/family why thrombolysis is contraindicated.
Administration of thrombolysis carries inherent risk of This conversation should be documented in the med-
bleeding complications, which can be lethal. Therefore, ical record.
patients must be properly screened for inclusion and
exclusion criteria. Patients and families must be counse- Communication
led quickly, but properly about the risks and benefits, and When communicating to an accepting or referring phy-
alternatives of thrombolytic therapy. The following points sician about this patient, consider including the key ele-
should be kept in mind: ments listed in Table 12.
 healthcare professionals from the American Heart Association/American
Clinical pearls
Stroke Association. Stroke. 2018;2018(49):e46–110. This is the most recent
update for early management of acute ischemic stroke from the AHA.
• In patients with symptoms upon awakening the LKW time is the time
4. Higashida R, Alberts MJ, Alexander DN, et al. Interactions within stroke
they went to bed
systems of care: a policy statement from the American Heart Association/
• In case of fluctuating symptoms determine if the patient was back to American Stroke Association. Stroke. 2013;44:2961–84.
baseline 5. Lima FO, Silva GS, Furie KL, et al. Field assessment stroke triage for
• In cases of stuttering symptoms the clock is reset only if the patient is emergency destination: a simple and accurate prehospital scale to detect
back to baseline large vessel occlusion strokes. Stroke. 2016;47:1997–2002.
6. Perez de la Ossa N, Carrera D, Gorchs M, et al. Design and validation of a
• With patients on direct oral anticoagulants, determine the last time they
prehospital stroke scale to predict large arterial occlusion: the rapid arte-
took their medication
rial occlusion evaluation scale. Stroke. 2014;45:87–91.
• IV tPA can be offered in several scenarios after weighing the risk and 7. Kim JT, Chung PW, Starkman S, et al. Field validation of the Los Angeles
benefit motor scale as a tool for paramedic assessment of stroke severity. Stroke.
• Low NIHSS is not a contraindication to thrombolysis 2017;48:298–306.
8. Jauch EC, Saver JL, Adams HP Jr, et al. Guidelines for the early manage-
• In patients with hypoglycemia, correct the blood glucose and deter- ment of patients with acute ischemic stroke: a guideline for healthcare
mine if the symptoms have resolved. If these are persistent, IV tPA could professionals from the American Heart Association/American Stroke
be administered Association. Stroke. 2013;44:870–947.
• Administer IV tPA as quickly and safely as possible. Many facilities admin- 9. Powers WJ, Derdeyn CP, Biller J, et al. 2015 American Heart Association/
ister IV tPA during the wait time between CT and CTA/CTP American Stroke Association focused update of the 2013 guidelines for
• Observing patients after thrombolysis to assess for clinical response in the early management of patients with acute ischemic stroke regarding
patients with LVO and mismatch profile is not required endovascular treatment: a guideline for healthcare professionals from
the American Heart Association/American Stroke Association. Stroke.
• Endovascular therapy 0–6 h = NIHSS ≥ 6, CTA/MRA with LVO and 2015;46:3020–35.
ASPECTS ≥ 6 10. *Demaerschalk BM, Berg J, Chong BW, et al. American telemedicine
• Endovascular therapy 6–24 h = NIHSS ≥ 6, CTA/MRA with LVO and CTP/ association: telestroke guidelines. Telemed E-Health. 2017;23:376–89. This
MR Perfusion with mismatch profile using DAWN or DEFUSE trial criteria paper elaborates the scientific evidence and rationale for the various inclu-
in anterior circulation strokes sion and exclusion criteria for tPA and forms the basis for the updated 2018
• Consider short-term dual antiplatelet therapy in patients with TIA and AHA guidelines.
ischemic stroke 11. Schwamm LH, Chumbler N, Brown E, et al. Recommendations for
the implementation of telehealth in cardiovascular and stroke care:
a policy statement from the American Heart Association. Circulation.
2017;135:e24–44.
12. Kostulas N, Larsson M, Kall TB, et al. Safety of thrombolysis in stroke mim-
Author details ics: an observational cohort study from an urban teaching hospital in
1
 Mount Carmel College of Nursing, Adult Gerontological Acute Care Nurse Sweden. BMJ Open. 2017;7:e016311.
Practitioner Program, Columbus, OH, USA. 2 Department of Neurology, The 13. Demaerschalk BM, Kleindorfer DO, Adeoye OM, et al. Scientific rationale
Ohio State University Wexner Medical Center, Columbus, OH, USA. 3 Depart- for the inclusion and exclusion criteria for intravenous alteplase in
ment of Neuroscience, Texas Health Dallas, Dallas, TX, USA. 4 College of Nurs- acute ischemic stroke: a statement for healthcare professionals from
ing and Healthcare Professions, Grand Canyon University, Phoenix, AZ, USA. the American Heart Association/American Stroke Association. Stroke.
5
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