Acute

Ischemic
Stroke
Marc Lapointe, PharmD
Professeur

Department of Clinical Pharmacy & Outcome Sciences

Medical University of South Carolina

Department of Neurosciences
College of Medicine
S.T.: a case in real-time …
p 81 year-old man

p PMX: atrial fibrillation, type 2 diabetes, BPH,

obesity (130 kg), dyslipidemia, hypertension

p PSX: none

p Social: Occasional smoker, occasional wine,

+RV, +tatouages

p CC: R upper/lower extremity hemiparesis,

facial droop, aphasia, and dysarthria
Brain Attack Team (BAT) called
p His wife witnessed onset of symptoms at
noon today after Monday Brunch

p Home Meds:
n Metformin 1,000 mg qd, amlodipine 10 mg qd,
rivaroxaban 20 mg qd, atorvastatin 40 mg qd (not
compliant – myalgia), Tamsulosin 0.4 mg qd

p ECG: atrial fibrillation, HR=120 bpm,

BP=190/95 mm Hg

p Patient scheduled to have a major dental

procedure next Monday (11/2) and medical
office told him to stop taking rivaroxaban 4
days ago (Monday)
BAT call in progress …
Please hold …
p NIH Stroke Scale
p Level of
Consciousness
p Questions
p Commands
p Best Gaze
p Visual
p Facial Palsy
p Motor – Arms & Legs
p Limb Ataxia
p Sensory
p Best Language
p Dysarthria
p Extinction / inattention
S.T.: a case in real-time …

p Laboratory results basic metabolic panel

and a CBC, are unremarkable,
p bedside INR = 1.4
p HA1C: Not ordered
p Lipid: not ordered
p TSH: not ordered
S.T.: a case in real-time …
p Patient is rushed to CT scanner (in
the E.R.)
CT Scan
CT Angiogram
CT Perfusion
 Warning
The next images can be
shocking or disturbing for some
viewers
ICH (No tPA)
SAH (No tPA)
No tPA (severe infarction)
BAT Cal in progress …

p What’s next for S.T. and his wife?

p Determine the therapeutic plan, eligibility

for IV tPA and/or interventions
Learning Objectives
p Describe the acute management of stroke
n 0-4.5 hours
n > 4.5 hours

p Recite indication and contraindications for IV r-tPA

p Summarize blood pressure management during the
management of acute stroke in the ER and ICU
p Summarize the medical management of uncomplicated
ischemic stroke patients before discharge
p Discuss Door-to-Needle , Time-window, Tissue-window
Academic Expectations
¨ Review learning objectives
¨ Chapter-38 (Pathophysiological Approach - Blue)
¨ Lecture will summarize clinical considerations
¨ Review and Study Figure 11-1
¨ Review and study tables 38-1, -2, -3, -4, -7, -8
¨ Complete self-assessment quiz (Chapter-38)
¨ Complete self-assessment quiz (NAPLEX Chapter-6)
¨ Monitor forum on MUSC BrightspaceCourse
¨ Complete self-directed learning activity
Principles of Treatment

u Early identification of stroke symptoms

u CT scan to rule out hemorrhage

u IV Thrombolytic (tPA) therapy within 4.5 hours

u Goal is 60 min
u Better outcomes (0-90 min)

u Secondary stroke prevention

Stroke Subtypes
• Subarachnoid (SAH)
Hemorrhagic 15% • Intracerebral (ICH)

Other 4%

Lacunar 21%
Cryptogenic 26%

Atherosclerotic Cardioembolic 17%

17%

Ischemic 85%

.
Hemorrhagic Stroke
u Intracerebral Hemorrhage (ICH)

u Subarachnoid Hemorrhage (SAH)

http://www.strokecenter.org/patients/ich.htm
Pre-Hospital Stroke Scale
1. Facial Droop 2. Arm Drift 3. Speech

“You can’t
teach an old
dog new
tricks.”

© American Heart Association.

Differential Diagnosis
u Head Trauma u Metabolic
Abnormalities
u Meningitis /
Encephalitis § Hyperglycemia
§ Hypoglycemia
u Intracranial Mass
u Tumor u Post cardiac-arrest
ischemia
u Subdural Hematoma
u Drug / narcotic
u Seizure
overdose
u Migraine
u Conversion disorder
Migraine vs. Stroke
Migraine Stroke / TIA

u 10 – 30 minutes u < 10 minutes

u Build up u Abrupt onset- Symptoms
develop over seconds

u Migration of symptoms u No migration

u Vision: flashing lights, u Vision loss
zig-zag lines
Specific therapeutic goals
p Reduce Infarct size
p Minimize stroke severity
p Timely restoration of blood flow
p Limit volume of unsalvageable tissue (core)
p Preserve blood perfusion in the penumbra
New Target:Stroke
“Door-To-Needle Time”
p 50% < 30 minutes
p 75% < 45 minutes
p 85% < 60 minutes
NIHSS
p Validated tool
p Stroke deficit
p 0-42
n Mild (0-5), limited benefit with tPA – relative to
the deficits experienced
n Moderate (6-15)
n Severe (>15)
Modified Rankin scale
p Disability status at discharge and 90 days
p 0-6
p Categorical data
 Stroke
Acute Management
(Time is Brain)
 How was tPA approved?
NINDS (National Institute of Neurological Disorders
and Stroke rt-PA Stroke Study Group)
Patients 624 patients, January 1991 – October 1994
IV alteplase (tPA) or placebo within 3 hours of
symptom onset

Outcomes 3 months: complete or near-complete recovery

à favorable odds ratio for tPA 1.7,
30% more likely to have minimal/no disability

Symptomatic ICH: 10x greater for tPA

6.4% for tPA, 0.6% for placebo
NEJM. 1995; 333: 1581-7.
What do we do after 3 hours?
ECASS 3 (European Cooperative Acute Stroke Study)
Patients 821 patients, 18 - 80 years old
IV alteplase (tPA) or placebo: 3 - 4.5 hours
(median time of treatment = 4 hours)
(excluded >80, DM/Stroke, Warfarin ?)
Outcomes Favorable outcome:
52% for tPA, 45% for placebo
OR 1.34, NNT = 14

Symptomatic ICH: 2.2% for tPA, 1.2% for

placebo
NEJM. 2008 Sept; 359 (13): 1317-29.
 Thrombolysis - r-tPA Indication
Ischemic stroke onset within 4.5 hours of drug administration

Deficit on NIHSS > 4 or potentially disabling deficit

(aphasia / hemianopia)

CT scan does not show hemorrhage / non-stroke etiology

Hypodensity not > 1/3 middle cerebral artery territory

Age > 18 years

r-tPA Contraindications
Stroke / head trauma within
3 months
Major surgery / serious
trauma within 14 days
Known Hx of ICH or ruptured
aneurysm
Sustained systolic BP > 185
Sustained diastolic BP > 110
Aggressive Tx to lower BP
Symptoms suggest SAH
GI / urinary tract hemorrhage
within 21 days
Arterial puncture at non-
compressible site within 7 days
Pt received heparin within 48
hours and has elevated PTT
Pt recently received warfarin
and INR > 1.7
Platelets < 100 K/cumm
Serum glucose < 50 or > 400
Recent lumbar puncture
r-tPA Order
Dose: 0.9 mg/kg (max dose 90 mg)

Bolus = 10% of total dose, given over 1 minute by physician

Continuous infusion = 90% of total dose, given over 60 min.

Blood pressure goals : SBP < 180 mmHg and DBP < 105
mmHg
Manage with labetalol OR hydralazine, can transition to
nicardipine in ICU
Suspect ICH if sudden HA, nausea, vomiting, or decreased
level of consciousness à stop tPA, page MD, head CT
Additional Recommendations
(Textbook update)

p Alteplase may be reasonable for patients

with mild, disabling stroke

p Benefit of alteplase is uncertain in patients

with severe stroke symptoms (NIHSS
score > 25)

p Treatment appears to be safe and may be

beneficial in:
n patients > 80, patients with INR ≤ 1.7, and
patients with both a prior stroke and diabetes
tPA Adverse Effect
p Intracranial Hemorrhage
n Rate of hematoma expansion: 40%
n 3-month mortality up to 60%
p Hemorrhagic conversion post-tPA (IV
n 2-7%
p Angioedema
n 1-5%
n Concurrent use of ACE (65%), already high level of
bradykinin
n ACE odd ratio = 4
n Plasminogen ->plasmin
n Histamine release and bradykinin
n Self-limiting and no effect on mRS or ICH
p Treatment of ICH in “Acute Care Therapeutics”
Wake-up Stroke
p 15-20% of AIS patients

p Routine MRI is time consuming and not cost-

effective when AIS patients within 4.5 hours

p Paradigm shift
n Time-window
n Tissue-Window (MRI to justify 4.5-24 hours)
n Functional benefit with imaging up to 24 hours
n MR WITNESS, WAKE UP, and EXTEND trials
Tenecteplase vs. Alteplase
p Longer half-life (22 minutes vs. 4 minutes),
p 14-fold increased specificity toward fibrin
p 80-fold increased resistance to plasminogen
activator inhibitor-1
p Single push
p More potent and faster fibrinolysis
p Lower systemic fibrinolysis
p Mild stroke or prior to thrombectomy?

p Great topic from Grand Round perhaps ?

Blood pressure management
p 70% have BP > 170/110 mm Hg

p Goals
n If IV tPA: < 185/110 mm Hg
n Post-tPA or thrombectemy: <180/105 mm Hg
n No intervention, permissive <220/110 mm Hg
 t-PA patient and Blood pressure
Pharmacotherapy Principles and Practice, 5e > Stroke
 
Marie A. Chisholm-Burns, Terry L. Schwinghammer, Patrick M. Malone, Jill M. Kolesar, Kelly C. Lee, P. Brandon Bookstaver+
 Table 11–2Blood Pressure (BP) Recommendations for Ischemic Stroke (Eligible for Alteplase)  
 

May use either labetalol 10–20 mg IV over 1–2 minutes (may repeat after 10 minutes) or nicardipine
Before treatment: If systolic BP >185 mm Hg or diastolic BP >110 mm Hg infusion 5 mg/hour (titrate up by 2.5 mg/hour every 5–15 minutes; maximum dose 15 mg/hour) or may
consider other agents (hydralazine, enalaprilat)

During and after treatment to maintain BP ≤ 180/105 mm Hg:

Use either labetalol 10 mg IV over 1–2 minutes followed by labetalol infusion 2–8 mg/min or
If systolic BP >180–230 mm Hg or diastolic BP >105–120 mm Hg nicardipine infusion 5 mg/hour (titrate up by 2.5 mg/hour every 5–15 minutes; maximum dose 15
mg/hour)

Nitroprusside 0.3–0.5 mcg/kg/min titrated by 0.5 mcg/kg/min to response; maximum dose 10
If BP not controlled or diastolic BP >140 mm Hg
mcg/kg/min

IV, intravenous.
 
Date of download: 10/30/20 from Pharmacotherapy Principles &Practice: ppp.mhmedical.com, Copyright © McGraw Hill. All rights reserved.
 
 

 
 
 Non-eligible t-PA patient & Blood
pressure
Pharmacotherapy Principles and Practice, 5e > Stroke
 
Marie A. Chisholm-Burns, Terry L. Schwinghammer, Patrick M. Malone, Jill M. Kolesar, Kelly C. Lee, P. Brandon Bookstaver+
 Table 11–3Blood Pressure (BP) Recommendations for Ischemic Stroke (Not Eligible for Alteplase)  
 

Systolic BP <220 mm Hg and diastolic BP <120 mm Hg Observe unless other end-organ involvement

Labetalol 10–20 mg IV over 1–2 minutes (may repeat every 10–20 minutes; maximum dose 300 mg)
Systolic BP >220 mm Hg or diastolic BP 121–140 mm Hg
or nicardipine infusion 5 mg/hour titrated to response

Nitroprusside 0.3–0.5 mcg/kg/min titrated by 0.5 mcg/kg/min to response; maximum dose 10
Diastolic BP >140 mm Hg
mcg/kg/min

IV, intravenous.
 
Date of download: 10/30/20 from Pharmacotherapy Principles &Practice: ppp.mhmedical.com, Copyright © McGraw Hill. All rights reserved.
 
 

 
 
Options for BP management
ENCHANTED, 2019
p Randomized trial
p Ischemic stroke
p N=2196
p SBP 130-140 Hg vs. < 180 mm Hg within
1 hour of admission
p Outcome: mRS at 90 days
p Results:
n No difference
n Lower rate of ICH (14.8% vs. 18.7%)
n No clear benefit. Not necessary or beneficial
 Monitoring of AIS Patients
Pharmacotherapy Principles and Practice, 5e > Stroke
 
Marie A. Chisholm-Burns, Terry L. Schwinghammer, Patrick M. Malone, Jill M. Kolesar, Kelly C. Lee, P. Brandon Bookstaver+
 Table 11–6Monitoring the Stroke Patient  
 
Treatment Parameter(s) Monitoring Frequency Comments

Ischemic Stroke

CT scan
Upon arrival
All stroke patients
Neurologic examination
Every 5 minutes × 3
BP

24 hours after alteplase infusion
CT scan
Alteplase
Every 15 minutes × 2 hours, every 30 min × 6
BP
hours, every 1 hour × 16 hours; then every shift

Neurological examination every 15 minutes × 2
hours, every 30 min × 6 hours, every 1 hour × 16
Neurologic function
hours; NIHSS 24 hours after alteplase infusion
and at discharge

Clinical signs of bleeding every 2 hours × 24
Bleeding
hours
Medical Complications
u VTE: DVT and PE
u Dysphagia and aspiration
u Pulmonary – pneumonia
u Cardiac – EKG changes, arrhythmias, increases in
cardiac enzymes, MI
u UTI, urologic & sexual dysfunction
u GI bleeding
u Falls / fractures
u Depression

www.uptodate.com
Conclusion
p Should you be in the ER for a shadowing
pharmacy experience and patient is taken to
MUSC for a brain attack …
p Describe
n 0-15 min
n 15-30 min
n 30-45 min
n Describe possible issues for medical &
medication errors
n Mixing tPA