Intravenous Recombinant Tissue Plasminogen Activator (tPA) and Endovascular Thrombectomy (EVT)

In this book, we will refer to recombinant tissue plasminogen activator as tPA, because that is what it is usually called in the busy emergency department. However, the reader should be aware that this drug is also referred to as rt-PA, t-PA, TPA, alteplase (generic name), or Activase or Actilyse (trade names).

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  Details of the tPA protocol can be found in Chapter 5.

  
  
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  Intravenous tPA within 3 hours of stroke onset is approved by the regulatory bodies (FDA in the USA, EMA in the EU) for acute ischemic stroke in the USA, European Union, and many other countries.

  
  
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  Intravenous tPA between 3 and 4.5 hours after stroke onset was effective in a randomized clinical trial and is incorporated in the guideline recommendations by the American Stroke Association (class I recommendation, level of evidence B)¹ and the European Stroke Organisation (class I recommendation, level of evidence A).²

  
  
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  EVT is a highly effective FDA-approved intervention for patients with large-vessel occlusion (LVO), namely the distal internal carotid or proximal middle cerebral arteries. EVT is covered in detail in Chapter 6.

Concurrent Diagnostic Testing

Determination of stroke etiology is usually deferred until after starting tPA therapy. However, while considering or instituting tPA, concomitant information about vascular and tissue status is important for deciding about the need for EVT. The following diagnostic tests may be helpful in determining the stroke mechanism; however, the need to do acute studies depends on a balance of availability of therapy, time requirement, clinical suspicion, and cost. See Chapter 4 for detailed descriptions of the following radiological tests:

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  Head CT should already have been done, as it is one of the vital first steps in the management of the stroke patient and helps to exclude hemorrhage.

  
  
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  CT angiography (CTA) can quickly provide a snapshot of the entire cerebral arterial anatomy, and can diagnose intracranial and extracranial stenoses, aneurysms, or dissections. It is the most frequently employed test for detecting LVO and EVT eligibility. In some centers, it may be necessary to know the patient’s creatinine prior to the administration of IV contrast, though this is no longer required in current guidelines. It is also necessary to exclude a contrast allergy.

  
  
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  CT perfusion (CTP) gives a spatial representation of cerebral perfusion. Software packages include measurement of time delay from bolus to arrival of dye into the brain and the amount of dye in the affected region compared to the opposite side. These parameters can be thresholded to reflect ischemic tissue at risk and tissue where flow is so low that irreversible damage is likely. However, CTP requires more contrast, more radiation, more patient cooperation, and a larger-bore peripheral IV access.

  
  
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  MR angiography (MRA) of the neck and circle of Willis provides the same information as CTA without risk of contrast. However, patients must be cooperative to hold still for several minutes, and those with a pacemaker and some with aneurysm clips or stents may not be eligible for MRI scanning.

  
  
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  Transcranial Doppler ultrasound (TCD) can be performed to detect occlusion, recanalization, and reocclusion of the large intracranial arteries in real time and can be brought to the patient’s bedside in the emergency department (Appendix 2). However, this test is usually not available in the ED, and it is not as accurate as CTA or MRA (see below) for establishing the presence and location of LVO.

  
  
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  MR imaging (MRI) of the brain can provide substantial information on stroke localization, age, bleeding, and tissue status. However, the same caveats apply as with MRA.

Maintenance of Cerebral Perfusion

To maximize brain perfusion through stenoses and collateral vessels, we maintain euvolemia and support blood pressure.

Do not treat hypertension acutely unless:

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   1. the patient is otherwise a tPA candidate

or

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   2. the patient has acute hypertensive end organ damage (congestive heart failure, myocardial infarction, hypertensive encephalopathy, dissecting aortic aneurysm, etc.)

or

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   3. systolic or diastolic pressures are above 220 or 120 mmHg, respectively.

If you are going to treat hypertension, consider using a short-acting IV agent that will wear off quickly or be turned off in case BP drops too much, such as:

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  labetalol (Trandate, Normodyne) 10–20 mg IV

  
  
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  nicardipine (Cardene) 5 mg/h IV infusion as initial dose; titrate to desired effect by increasing 2.5 mg/h every 5 minutes to maximum of 15 mg/h

Goal: blood pressure reduction by 10–15%.or

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  treat hypertension slowly with oral or enteral rather than intravenous antihypertensives.

Don’t forget to write BP goals for the nurses to follow that include both lower and upper limits for SBP and DBP.

In the absence of controlled prospective data, there is some consensus but still significant uncertainty about what levels of blood pressure to treat, how fast to lower the pressure, and what drugs to use (see Chapter 8). In tPA candidates, we follow the guidelines in Table 3.1; we use nicardipine most commonly in the ED and during the first 24 hours to titrate blood pressure smoothly to desired levels.

Other options for maintenance of cerebral perfusion include:

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  Normal saline for IV fluids – to maintain euvolemia and because it is isotonic and will not cause fluid shifts:

  
  
  
  
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     ▪ normal saline 500 mL bolus over 20–30 minutes

  
  
  
  
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  Adjust head position. A recent study suggested no benefit of routine head lowering, but included mainly minor strokes.³ In patients with LVO or who are fluctuating, laying the head of the bed flat may be beneficial.

Antiplatelet and Anticoagulant Therapy as an Acute Treatment for Ischemic Stroke

Both antiplatelet and anticoagulant therapy are often considered in the acute therapy of ischemic stroke, and one or both may be appropriate, but randomized trials have shown that anticoagulants should not be routinely employed acutely. Trials have shown that antiplatelets have only a modest benefit, and no studies have yet shown the benefit of urgent antiplatelet treatment.

Related posts:

Chapter 6 – Endovascular Therapy Chapter 7 – Neurological Deterioration in Acute Ischemic Stroke Chapter 5 – Intravenous Thrombolysis Chapter 15 – Stroke Rehabilitation Chapter 14 – Organization of Stroke Care Chapter 13 – Subarachnoid Hemorrhage