William C. Barrow, MD
CHAPTER CONTENTS
◦Emergent Evaluation and Management
– Special Considerations in IV tPA therapy
– Therapy
OVERVIEW
In 2011, stroke dropped from the third leading cause of death to the fourth in the United States. Much of this is likely related to improvements in treatment options for acute stroke care and better collaboration between emergency medicine, radiology, and neurology.
ISCHEMIC STROKE
Between 80% and 85% of strokes are ischemic, whether due to embolism, large-vessel disease, or small-vessel thrombotic occlusion. We will consider both acute and subacute ischemic stroke. (Stroke syndromes were discussed in Chapter 4.)
Emergent Evaluation and Management
The approach to acute ischemic stroke (AIS) begins with a rapid and thorough evaluation to determine diagnosis and eligibility for reperfusion therapy. Figure 16.1 presents a flowchart but evaluation of every patient is individualized.
FIGURE 16.1 Flowchart for acute stroke
Key first actions:
History will ultimately be complete, but in the ED as part of the urgent evaluation we need the basics:
•Best history of the event: With sources as available from patient, EMS, family, friends, and other sources as immediately available
•Past medical history: As available from preceding sources and also as evidenced from brief exam (e.g., PPM, sternotomy scar, dialysis shunt)
•Electronic medical record (EMR) review: For evidence of prior medical conditions predisposing to stroke as well as for non-stroke conditions that should be considered.
Initial examination is far simpler than the subsequent comprehensive neurologic exam. Details of the exam are governed by present findings, but, in general, we recommend the following basics on presentation:
•Mental status: Alertness, orientation
•Language: Comprehension, expression
•Motor: Strength and tone in all extremities
•Sensory: Focused assessment considering results of motor exam
•Reflex: Tendon reflexes and plantar responses
•Ocular: Pupils, ocular movements, visual fields
•Medical: Cardiac, pulmonary, peripheral vascular, skin
Examples of scenarios where the history and exam are specifically tailored to the presentation can include:
•Hemiparesis with inconsistent findings: Consideration of atypical stroke, demyelinating disease, migraine, or functional weakness. Query specifically about headache, previous events, stressors. Review EMR for previous related conditions. Perform additional examination for deficits of multiple lesions or inconsistency.
•Encephalopathy: Marked encephalopathy raises concern over multifocal acute strokes, brainstem or cerebellar infarct with edema, or intracranial hemorrhage. Nonstroke etiologies are considered including intoxication, electrolyte or metabolic abnormality (e.g., high or low glucose, renal failure, hepatic failure), seizure, head injury.
•Ataxia: Ataxia in the absence of other neurologic deficits suggests cerebellar lesion, but alternatives include intoxication, paraneoplastic cerebellar degeneration.
•Seizure: Seizure can be subtle and occasionally nonconvulsive. If seizures are considered, then look for nystagmus or even subtle limb movements.
The National Institutes of Health Stroke Scale (NIHSS) is performed whenever stroke is suspected, usually by nursing or physician staff who are specifically trained in its performance and interpretation. Details of the NIHSS are presented in Chapter 39.
Computed tomography (CT) of the brain without contrast is performed urgently, within a few minutes of arrival. Some facilities have direct-to-CT protocols for suspected stroke. This requires coordination between EMS and ED staff with urgent notification of the stroke team.
Lab studies on presentation typically include BMP or CMP, CBC, and coagulation studies. Bedside glucose is commonly performed to rule out marked hyper- or hypoglycemia.
This initial evaluation is to determine if the patient is a candidate for immediate reperfusion therapy with intravenous tissue plasminogen activator (tPA) and/or endovascular therapy.
Key points in deciding to proceed with reperfusion therapies:
•Time patient was last known normal
•Significant past medical history
•Coagulation studies if patient may be on anticoagulation therapies
•Neuroimaging: CT of the head without contrast.
•Risk vs. benefits: 3–6% risk of an intracerebral hemorrhage (ICH) and 2–3% risk of a fatal ICH
IV Thrombolytics
Inclusion criteria for IV tPA (<3 hours from symptom onset): Intravenous tPA is indicated for adult (≥ 18 years of age) patients with acute ischemic stroke if it can be given within 3 hours from onset of symptoms.
Exclusion criteria for IV tPA (<3 hours of symptom onset): Initial exclusion criteria were quite lengthy and limited the number of patients who qualified for IV tPA. Revised guidelines were published in 2013 and 2016, and a new package insert was released in February 2015.1 These narrowed the contraindications significantly; this, however, opened the door for inconsistent interpretation of some criteria:
•Contraindication for bleeding diathesis
•Warning for recent intracerebral hemorrhage
•Warning for blood pressure 175/110
•Contraindication for subarachnoid hemorrhage
•Warning for pregnancy category C
The 2016 guidelines further liberalized criteria for administration of IV tPA. These are freely available online and should be in every neurologists files; only a selection of the recommendations is discussed here.1 Among the changes were:
•Stroke severity: Initial guidelines cautioned against using tPA in patients with severe stroke or with mild stroke. 2016 guidelines recommend consideration in patients with severe stroke and in patients with mild stroke which is disabling.
•Clinical improvement: Initial guidelines did not encourage tPA administration for patients who were improving. 2016 guidelines recommend considering tPA despite improvement if the deficit is still disabling.
•Timing of administration: Initial guidelines recommended treatment only within the 3 hour-from-symptoms-onset time window. 2013 guidelines recommended consideration of tPA in the 3-4.5 hour window but excluding age > 80 years, patients with NIHSS > 25, imaging evidence of MCA stroke involving more than 1/3rd of the distribution, or patients with a history of both previous stroke and diabetes. The 2016 guidelines liberalized consideration of use in the 3-4.5 hour window to include selected patients over 80 years of age and in select patients with a history of prior stroke and diabetes.
•Pregnancy: Initial guidelines had pregnancy as a contraindication. New guidelines recommend consideration of tPA for moderate to severe stroke, with urgent involvement the OB physician.
•Myocardial infarction: Initial guidelines recommended not giving tPA with MI within 3 months. New guidelines recommend consideration if AIS and MI are concurrent, and also if MI has been within 3 months under certain circumstances.
•Seizure: Initial guidelines recommended not giving tPA if there was a seizure at onset. New guidelines recommend considering tPA if residual deficit is not felt to be due to postictal effect.
Administration of thrombolytic: The only Federal Drug Administration (FDA)-approved IV medication for acute stroke is recombinant tPA. Once the decision is made to proceed with IV tPA, 0.9 mg/kg of medication is mixed for a maximum dose of 90 mg. The first 10% of the total amount mixed is given as a bolus. The remaining 90% is infused over 1 hour.
Patients must be monitored closely over the next few hours for signs of bleeding or acute neurological change. Any acute change in neurological status requires stopping the infusion of tPA and obtaining a stat CT of the head to rule out bleeding.
Precautions should be used in patients who are taking concomitant angiotensin-converting enzyme (ACE) inhibitors because angioedema can occur during or immediately after the administration of tPA. If it develops, tPA infusion should be stopped, and medical treatment with corticosteroids, antihistamines, and possibly epinephrine be considered.2
Patients who have received either IV thrombolytics and/or endovascular therapies should be monitored in an ICU or stroke unit for at least 24 hours after treatment.
Post IV t-PA care:
•No anticoagulants or antiplatelet agents for 24 hours following tPA infusion
•Blood pressure control of less than 180/100 for the first 24 hours post infusion
•No arterial punctures, invasive procedures, or intramuscular injunctions for 12 hours post infusion
•Repeat CT scan of the head or MRI of the brain before initiating antiplatelet or anticoagulant therapy to rule out asymptomatic hemorrhage
•Frequent evaluation by nursing staff of the patient’s neurological status
If all the preceding criteria are not available at the administering facility, transfer to a stroke center should be arranged immediately.
Special Considerations in IV tPA therapy
Patients with improving deficits are sometimes not given tPA because of initial recommendations that suggested that treatment was not needed for patients showing rapid improvement. However, we now recommend consideration if the patient has significant deficit even if improved.
Patients with aphasia and no other deficit are functionally devastated yet can have a low NIHSS. While strict adherence to original recommendations resulted in these patients not being treated, we now recommend consideration of tPA even if aphasia is the only deficit.
Informed consent may not be obtainable. If no family is available and the patient cannot give informed consent due to aphasia, then administration of IV-tPA within the 3-hour window is appropriate since it is adherent to accepted medical practice. Treatment in the extended 3–4.5 hour window is not FDA approved, so, in our working practice, we do not recommend this without informed consent from patient or family. Likewise, endovascular therapy within 6 hours can be considered without necessitating informed consent, but beyond this time window in our practice we ask that consent be obtained.
Endovascular Therapies
Multiple clinical trials have been published recently showing added benefit of endovascular therapies in patients with amenable occlusions. Most patients in these studies, however, also received IV tPA, which currently remains the “gold standard” for treatment of acute stroke. Endovascular therapy should be considered especially in patients seen within the 6-hour window even if they are receiving tPA, and we extend that consideration beyond 6 hours depending on clinical details.
IV Heparin
Presently, there is no clinical evidence supporting the routine use of IV heparin in acute ischemic stroke. However, IV heparin is frequently used in acute/subacute stroke patients with simultaneous myocardial infarction, pulmonary embolism, or other medical comorbidities that necessitate urgent anticoagulation.
Extra caution and close monitoring of neurological status is needed in patients with large infarcts receiving IV heparin due to the risk of hemorrhagic conversion of the ischemic region.
Antiplatelets
Aspirin is recommended by AHA/ASA guidelines3 for patients with AIS unless contraindicated (e.g., coagulopathy, significant hemorrhage). In most facilities, aspirin is administered in the ED as soon as the CT demonstrates no hemorrhage if the patient is not a candidate for IV tPA or endovascular treatment. If the patient does receive treatments, then aspirin is withheld for 24 hours.
Clopidogrel does not have the supportive data that aspirin does for AIS and is not recommended if aspirin can be used.
Aggrenox is a combination of aspirin and dipyridamole and is FDA approved for secondary prevention of AIS and transient ischemic attack (TIA).
Stroke Mimics
Several other neurological conditions can present with acute to subacute focal deficits in addition to infarct. A thorough stroke workup should be performed while alternative diagnoses are considered. The suspicion of a stroke mimic should not preclude the administration of IV thrombolytics if indications for IV tPA are present and contraindications have been ruled out. Luckily, the risk of hemorrhage from tPA in patients with most stroke mimics is low. Common stroke mimics include:
•Mass lesion (no tPA if responsible mass seen on CT)
•Conversion reaction and malingering
Clues to stroke mimic include:
•Gradual onset and progression may suggest migraine, demyelinating lesion, or tumor.
•Headache suggests migraine or tumor but can occur in AIS.
•Fever suggests encephalitis but can occur with stroke from septic emboli.
Chapter 4 discusses in more detail the differential diagnosis of focal motor and sensory symptoms.
Post-Acute Evaluation
Post-acute evaluation begins as soon as emergent management of AIS is initiated. This includes the following elements:
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