Reperfusion Therapy, Cerebral, Emergency Medicine

Basics

Description

An ischemic cerebrovascular accident (CVA), or stroke, is an acute, sudden or gradual, interruption of regional cerebral blood supply
Cerebral reperfusion therapy involves:
- Administration of an IV thrombolytic agent to rapidly dissolve a thromboembolic occlusion
- Site-specific endovascular intra-arterial thrombolysis
- Mechanical clot removal

Etiology

Thrombotic CVA is from an in situ thrombosis:
- At an ulcerated atherosclerotic plaque or other prothrombotic endothelial abnormality
- From hypercoagulable states:
  - Antithrombin III, protein C or S deficiency
- From sludging:
  - Sickle cell disease
  - Polycythemia vera
Embolic CVA is caused by acute obstruction by an embolus from:
- Cardiac mural thrombus formed in:
  - Atrial fibrillation
  - Hypokinetic ventricle (MI, cardiomyopathy)
  - Ventricular aneurysm
- An abnormal or prosthetic cardiac valve
- Aortic, carotid, or cerebrovascular atherosclerotic plaques
Other occlusive events include:
- Vascular dissection in aorta, cerebral, vertebral, carotid, or innominate arteries
- Cerebral vasospasm induced by:
  - Subarachnoid hemorrhage (SAH)
  - Vasoconstrictive agents (e.g., cocaine)

Diagnosis

Signs and Symptoms

History

Acute focal neurologic symptoms presenting within 4 " 5 hr of onset
Time of symptom onset is critical:
- If time of onset cannot be firmly established, the time the patient was last known normal should be used as a surrogate
Historical elements that may suggest an etiology other than routine thromboembolic stroke:
- Neck injury in carotid or vertebral dissection
- Tearing back pain in aortic dissection
- Drug abuse in vasospastic occlusions

Physical Exam

Consider reperfusion therapy for symptoms and signs consistent with a distinct vascular supply territory
Middle cerebral artery:
- Contralateral hemiplegia and hemisensory deficits (upper > lower)
- Contralateral homonymous hemianopsia
- Expressive or receptive aphasia (if in dominant hemisphere)
- Contralateral neglect
Posterior cerebral artery:
- Cortical blindness in half the visual field
- Visual agnosia (inability to recognize and identify persons and objects)
- Thalamic syndromes:
  - Abnormal movements (chorea or hemiballismus)
  - Hemisensory deficit
Vertebrobasilar system:
- Impaired vision, visual field defects
- Nystagmus, vertigo, dizziness
- Facial paresthesia, dysarthria
- Cranial nerve palsies
- Contralateral sensory deficits (pain and temperature)
- Limb ataxia, abnormal gait
Anterior cerebral artery:
- Contralateral hemiplegia and hemisensory deficits (lower > upper)
- Apraxia
- Confusion, impaired judgment
Lacunar (deep subcortical):
- Pure motor hemiplegia (most common), or pure sensory hemiplegia
- Dysarthria with hand ataxia (clumsy hand), or dysarthria with facial weakness
- Ataxic hemiparesis
The National Institutes of Health Stroke Scale (NIHSS) can be used to delineate severity of a CVA as follows (total of subcategory scores):
- 1a. Level of consciousness (LOC): Alert = 0; drowsy = 1; stuporous = 2; coma = 3
- 1b. LOC questions: Answers both correctly = 0; 1 correctly = 1; none correct = 2
- 1c. LOC commands: Obeys both correctly = 0; 1 correctly = 1; none correctly = 2
- 2. Best gaze: Normal = 0; partial gaze palsy = 1; forced deviation = 2
- 3. Visual: No visual loss = 0; partial hemianopia = 1; complete hemianopia = 2; bilateral hemianopia = 3
- 4. Facial palsy: Normal, symmetric = 0; minor paralysis = 1; partial paralysis = 2; complete paralysis = 3
- 5 to 8. Best motor (computed for each arm and leg): No drift = 0; drift = 1; some effort against gravity = 2; no effort against gravity = 3; no movement = 4
- 9. Limb ataxia: Absent = 0; present in 1 limb = 1; present in 2 or more limbs = 2
- 10. Sensory (pinprick): Normal = 0; partial loss = 1; dense loss = 2
- 11. Best language: No aphasia = 0; mild to moderate aphasia = 1; severe aphasia = 2; mute = 3
- 12. Dysarthria: Normal articulation = 0; mild to moderate dysarthria = 1; unintelligible = 2
- 13. Neglect/inattention: No neglect = 0; partial neglect = 1; complete neglect = 2

Essential Workup

Essential Labs

Stat bedside blood glucose testing
CBC, prothrombin time (PT)/partial thromboplastin time (PTT)
- To assess thrombolytic therapy risk in patients at risk of coagulopathy

Essential Imaging

Immediate noncontrast head CT scan:
- Can be part of a multimodal imaging protocol
- Can reveal other etiologies of symptoms (such as hemorrhage, tumor)
- Very likely normal in the hours after symptom onset:
  - Early signs of ischemia (e.g., edema) should prompt a re-evaluation of time of onset

Diagnosis Tests & Interpretation

EKG to assess for dysrhythmia, pericarditis, MI
Additional Labs

Serum electrolytes, BUN, creatinine
Urine pregnancy test
Urine toxicology screen
Liver function tests in patients prone to liver dysfunction

Additional Imaging

Multimodal MRI (with perfusion- and diffusion-weighted protocols):
- Can detect ischemic CVA almost immediately after onset
Perfusion brain CT can reveal a perfusion deficit immediately after onset
MR angiography or CT angiography can provide anatomical information
Carotid US
CXR

Differential Diagnosis

Intracranial hemorrhage (ICH) or SAH
Seizure
Complex migraine
Bell palsy or other focal neuropathies
Hypoglycemia and other metabolic abnormalities
Cerebral venous sinus thrombosis
Intracranial neoplasm
Intracranial trauma
Meningitis, encephalitis, or brain abscess
Vasculitis
Air embolism or decompression illness
Spinal cord lesion
Psychogenic

Treatment

Pre-Hospital

Assess for deficits:
- Dysarthria, facial weakness
- Arm or leg weakness
Notify and mobilize ED and hospital resources
Test blood glucose:
- Hypoglycemia can mimic a CVA
- Treat hypoglycemia with dextrose

Initial Stabilization/Therapy

Supplemental oxygen to correct hypoxia (pulse ox <94%)
RSI for airway protection or ventilatory insufficiency if needed
IV access and NS bolus to correct hypotension
Cardiac monitoring and pulse oximetry

Ed Treatment/Procedures

Exclude other diagnoses in the differential
Thrombolytic therapy should be reserved for thromboembolic ischemic strokes
Inclusion criteria for IV thrombolytic therapy:
- Age ≥18 yr of age
- Defined onset of symptoms within 4.5 hr
- No hemorrhage on noncontrast head CT
Absolute contraindications to IV thrombolytic therapy:
- CVA, serious brain injury, or intracranial surgery within previous 3 mo
- Prior ICH
- Clinical presentation consistent with SAH
- Arterial puncture at noncompressible site in previous 7 days
- Active bleeding on exam
- Uncontrollable HTN >185/110 mm Hg
- Known bleeding diathesis such as:
  - Platelet count <100,000/mm3 (if no history of thrombocytopenia, tissue plasminogen activator [tPA] can be initiated before platelet count, but should be discontinued if it is low)
  - Heparin within 48 hr, with elevated aPTT
  - Current anticoagulant use with an INR >1.7, or PT >15 sec
- Blood glucose <50 mg/dL
- Hypodensity in >1/3 cerebral hemisphere on CT
Relative contraindications to IV thrombolytics (weigh risk against benefit):
- Major surgery or trauma within previous 14 days
- Mild or resolving neurologic symptoms
- GI or GU bleeding within 21 days
- Seizure at the time stroke was observed
- Acute MI within previous 3 mo
Treat BP >185/110 mm Hg with 1 " 2 doses of labetalol, nicardipine, or other appropriate agent:
- Do not aggressively normalize BP
- Stroke patient may be dependent on an elevated mean arterial pressure for cerebral perfusion
- Avoid thrombolytic therapy if BP cannot be reduced to ≤180/110 mm Hg with minimal intervention
Administer IV tPA; alteplase
Avoid antiplatelet agents and anticoagulants for 24 hr
Monitor arterial BP during the 1st 24 hr after treatment with tPA and aggressively treat an SBP >180 mm Hg or a DBP >105 mm Hg:
- Check BP every 15 min for 2 hr, then every 30 min for 6 hr, then every hour for 24 hr
- Keep BP <180/105 mm Hg using medication such as labetalol or nicardipine
- Consider nitroprusside for HTN unresponsive to labetalol or nicardipine, or for a DBP >140 mm Hg
Monitor for signs of ICH:
- Decreased LOC
- Increased weakness
- Headache
- Acute HTN or tachycardia
- Nausea or vomiting
If ICH suspected, obtain an emergent head CT to confirm diagnosis:
- If present, treat as follows:
  - Discontinue tPA
  - Obtain blood samples for PT, PTT, platelet count, fibrinogen level
  - Prepare cryoprecipitate, fibrinogen, and platelets, and infuse as needed
  - Obtain neurosurgical consultation
Intra-arterial or mechanical recanalization may be considered for selected patients
- Though not as well studied as IV tPA, they may be administered out to 6 hr from onset

For patients presenting between 3 and 4.5 hr of onset; there are additional exclusion criteria for IV tPA:
- Age >80 yr
- Oral anticoagulant use (regardless of INR)
- NIHSS >25 or >1/3 MCA territory involved
- History of previous stroke and diabetes
There is up to a 6% risk of ICH with tPA that goes up significantly in patients with NIHSS >20

Medication

First Line

Alteplase (tPA): 0.9 mg/kg IV, max. 90 mg, over 1 hr:
- Give 10% of dose as a bolus over 1 min.
- Immediately follow with the remainder, infused over the subsequent 59 min
Labetalol: 10 mg IV over 1 " 2 min; then, if needed:
- Repeat or double dose q10 " 20min up to a max. of 300 mg, or
- Start a drip at 2 " 8 mg/min
Nicardipine: 5 mg/h as a drip; titrate upward in 2.5 mg/h increments every 5 min, up to a max. of 15 mg/h

Second Line

Nitroprusside: 0.5 " 1 ¼g/kg/min, continuous IV drip, titrated to BP parameters
Cryoprecipitate and fibrinogen: 6 " 8 U IV
Platelets: 6 " 8 U IV

Follow-Up

Disposition

Admission Criteria
All patients given reperfusion therapy for a CVA should be admitted to an intensive care setting for frequent neurologic checks and vital sign assessments.
Issues for Referral
Not applicable

Pearls and Pitfalls

Be specific in eliciting time of onset; patient or family may note "time of onset " as the time the stroke was 1st recognized (e.g., upon awakening from sleep)
tPA has a plasma half-life of <5 min; a delay between bolus and infusion, or pause in the infusion, may result in a decrease in plasma levels and effectiveness
"Time is brain " (and hemorrhage); initiate treatment as quickly as possible, even if the patient presents early

Additional Reading

Jauch EC, Cucchiara B, Adeoye O, et al. Part 11: Adult stroke: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation. 2010;122:S818 " S828.
Lansberg MG, O 'Donnell MJ, Khatri P, et al. Antithrombotic and thrombolytic therapy for ischemic stroke: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141:e601S " e636S.
Lees KR, Bluhmki E, von Kummer R, et al. Time to treatment with intravenous alteplase and outcome in stroke: An updated pooled analysis of ECASS, ATLANTIS, NINDS, and EPITHET trials. Lancet. 2010;375:1695 " 1703.

Codes

ICD9

434.01 Cerebral thrombosis with cerebral infarction
434.11 Cerebral embolism with cerebral infarction
434.91 Cerebral artery occlusion, unspecified with cerebral infarction

ICD10

I63.9 Cerebral infarction, unspecified
I63.30 Cerebral infarction due to thombos unsp cerebral artery
I63.40 Cerebral infarction due to embolism of unsp cerebral artery
I63.00 Cerebral infarction due to thombos unsp precerebral artery
I63.10 Cerebral infarction due to embolism of unsp precerb artery

SNOMED

230690007 Cerebrovascular accident (disorder)
426347000 thrombolytic therapy (procedure)
371040005 Thrombotic stroke (disorder)
371041009 Embolic stroke (disorder)

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