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Reperfusion Therapy, Cerebral, Emergency Medicine

Basics

Description

- 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

- 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

- 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

- 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

- 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

- Monitor for signs of ICH: - Decreased LOC - Increased weakness - Headache - Acute HTN or tachycardia - Nausea or vomiting

- 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

  • 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 occlusionSite-specific endovascular intra-arterial thrombolysisMechanical clot removal

Etiology

  • Thrombotic CVA is from an in situ thrombosis:At an ulcerated atherosclerotic plaque or other prothrombotic endothelial abnormalityFrom hypercoagulable states:Antithrombin III, protein C or S deficiencyFrom sludging:Sickle cell diseasePolycythemia vera
  • Embolic CVA is caused by acute obstruction by an embolus from:Cardiac mural thrombus formed in:Atrial fibrillationHypokinetic ventricle (MI, cardiomyopathy)Ventricular aneurysmAn abnormal or prosthetic cardiac valveAortic, carotid, or cerebrovascular atherosclerotic plaques
  • Other occlusive events include:Vascular dissection in aorta, cerebral, vertebral, carotid, or innominate arteriesCerebral 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 dissectionTearing back pain in aortic dissectionDrug 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 hemianopsiaExpressive or receptive aphasia (if in dominant hemisphere)Contralateral neglect
  • Posterior cerebral artery:Cortical blindness in half the visual fieldVisual agnosia (inability to recognize and identify persons and objects)Thalamic syndromes:Abnormal movements (chorea or hemiballismus)Hemisensory deficit
  • Vertebrobasilar system:Impaired vision, visual field defectsNystagmus, vertigo, dizzinessFacial paresthesia, dysarthriaCranial nerve palsiesContralateral sensory deficits (pain and temperature)Limb ataxia, abnormal gait
  • Anterior cerebral artery:Contralateral hemiplegia and hemisensory deficits (lower > upper)ApraxiaConfusion, impaired judgment
  • Lacunar (deep subcortical):Pure motor hemiplegia (most common), or pure sensory hemiplegiaDysarthria with hand ataxia (clumsy hand), or dysarthria with facial weaknessAtaxic 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 = 31b. LOC questions: Answers both correctly = 0; 1 correctly = 1; none correct = 21c. LOC commands: Obeys both correctly = 0; 1 correctly = 1; none correctly = 22. Best gaze: Normal = 0; partial gaze palsy = 1; forced deviation = 23. Visual: No visual loss = 0; partial hemianopia = 1; complete hemianopia = 2; bilateral hemianopia = 34. Facial palsy: Normal, symmetric = 0; minor paralysis = 1; partial paralysis = 2; complete paralysis = 35 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 = 49. Limb ataxia: Absent = 0; present in 1 limb = 1; present in 2 or more limbs = 210. Sensory (pinprick): Normal = 0; partial loss = 1; dense loss = 211. Best language: No aphasia = 0; mild to moderate aphasia = 1; severe aphasia = 2; mute = 312. Dysarthria: Normal articulation = 0; mild to moderate dysarthria = 1; unintelligible = 213. 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 protocolCan 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 weaknessArm or leg weakness
  • Notify and mobilize ED and hospital resources
  • Test blood glucose:Hypoglycemia can mimic a CVATreat 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 ageDefined onset of symptoms within 4.5 hrNo hemorrhage on noncontrast head CT
  • Absolute contraindications to IV thrombolytic therapy:CVA, serious brain injury, or intracranial surgery within previous 3 moPrior ICHClinical presentation consistent with SAHArterial puncture at noncompressible site in previous 7 daysActive bleeding on examUncontrollable HTN >185/110 mm HgKnown 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 aPTTCurrent anticoagulant use with an INR >1.7, or PT >15 secBlood glucose <50 mg/dLHypodensity in >1/3 cerebral hemisphere on CT
  • Relative contraindications to IV thrombolytics (weigh risk against benefit):Major surgery or trauma within previous 14 daysMild or resolving neurologic symptomsGI or GU bleeding within 21 daysSeizure at the time stroke was observedAcute 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 BPStroke patient may be dependent on an elevated mean arterial pressure for cerebral perfusionAvoid 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 hrKeep BP <180/105 mm Hg using medication such as labetalol or nicardipineConsider nitroprusside for HTN unresponsive to labetalol or nicardipine, or for a DBP >140 mm Hg
  • Monitor for signs of ICH:Decreased LOCIncreased weaknessHeadacheAcute HTN or tachycardiaNausea or vomiting
  • If ICH suspected, obtain an emergent head CT to confirm diagnosis:If present, treat as follows:Discontinue tPAObtain blood samples for PT, PTT, platelet count, fibrinogen levelPrepare cryoprecipitate, fibrinogen, and platelets, and infuse as neededObtain neurosurgical consultation
  • Intra-arterial or mechanical recanalization may be considered for selected patientsThough 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 yrOral anticoagulant use (regardless of INR)NIHSS >25 or >1/3 MCA territory involvedHistory 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, orStart 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.

See Also (Topic, Algorithm, Electronic Media Element)

  • Cerebral Vascular Accident
  • Transient Ischemic Attack

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)