1. ICU Book Chapter 46 ACUTE STROKE
Reporter Jau-Jia Sung

2. DEFINITIONS

3. Stroke
An acute brain disorder of vascular origin accompanied by neurological dysfunction that persists for longer than 24 hours.
Classification
Ischemic stroke accounts for 87% of all strokes : 80% of ischemic strokes are thrombotic strokes, and 20% are embolic strokes.
Hemorrhagic stroke accounts for 13% of all strokes: 97% of hemorrhagic strokes involve intracerebral hemorrhage, and 3% are the result of subarachnoid hemorrhage.

4. Transient Ischemic Attack
A transient ischemic attack (TIA) is an acute episode of ischemia with focal loss of brain function that lasts less than 24 hours.
The feature that distinguishes TIA from stroke is the reversibility of clinical symptoms in TIAs.
This does not apply to reversibility of cerebral injury, because one-third of TIAs are associated with cerebral infarction.

5. INITIAL EVALUATION

6. Each minute of cerebral infarction results in the destruction of 1
Each minute of cerebral infarction results in the destruction of 1.9 million neurons and 7.5 miles of myelinated nerves, and continued tissue destruction eventually leads to a point where reperfusion of occluded arteries with thrombolytic therapy will not promote neurological recovery.
This point occurs 4–5 hours after stroke onset, where the benefit from thrombolytic therapy is lost.

7. Bedside Evaluation

8. Bedside Evaluation Mental Status
Most cerebral infarctions are unilateral, and do not result in loss of consciousness.
When focal neurological deficits are accompanied by coma, the most likely conditions are intracerebral hemorrhage, brainstem infarction, or nonconvulsive seizures.

9. Bedside Evaluation APHASIA
Injury in the left cerebral hemisphere (which is the dominant hemisphere for speech in 90% of patients) produces aphasia, which is a disturbance in the comprehension and/or formulation of language.
Patients with aphasia can have difficulty with verbal comprehension (receptive aphasia), or difficulty with verbal expression (expressive aphasia), or both (global aphasia).

10. Bedside Evaluation Sensorimotor Loss
The hallmark of injury involving one cerebral hemisphere is weakness on the opposite or contralateral side of the face and body (i.e., hemiparesis).
The presence of hemiparesis or isolated limb weakness creates a high index of suspicion for stroke (or TIA), but focal limb weakness can be the result of nonconvulsive status epilepticus, and hemiparesis has been reported in patients with hepatic and septic encephalopathy.

11. Stroke Mimics
For patients admitted to the hospital with a suspected stroke based on clinical findings, as many as 30% of the patients will have another condition that mimics an acute stroke.
The most common stroke mimics are seizures, sepsis, metabolic encephalopathies, and space-occupying lesions (in that order).
Since stroke is primarily a clinical diagnosis, at least in the first 24–48 hours, stroke mimics are a source of excessive hospital admissions (and thrombolytic therapy) for suspected stroke.

12. NIH Stroke Scale
The NIHSS evaluates 11 different aspects of performance, and rates each performance with a number from zero to 3 or 4.
The total score is a measure of the severity of illness, and ranges from zero (best performance) to 41 (worst performance).
A score of 22 or higher generally indicates a poor prognosis.

13. Diagnostic Imaging

14. Computed Tomography
Noncontrast computed tomography (NCCT) is a reliable method for visualizing intracranial hemorrhage, as shown in Figure 46.2.
This reliability is particularly important in the decision to administer thrombolytic therapy, which is contraindicated if NCCT reveals intracranial bleeding.
The sensitivity of NCCT for intracranial hemorrhage is close to 100%.

15. Failure to recognize the hypoactive form of delirium may explain why the diagnosis of delirium is missed in as many as 75% of patients.

16. Computed Tomography
NCCT is not a reliable method for visualizing ischemic changes.
One-half of ischemic strokes are not apparent on NCCT, and the diagnostic yield is even less in the first 24 hours after an acute stroke (when infarct size is the smallest).
A negative CT scan does not eliminate the possibility of an ischemic stroke.

18. Magnetic Resonance Imaging
MRI with diffusion-weighted imaging (DWI) is the most sensitive and specific technique for the detection of ischemic stroke.
This technique, which is based on water movement through tissues, can detect ischemic changes within 5–10 minutes after onset, and it has a sensitivity of 90% for the detection of ischemic stroke in the early period after stroke onset.
If the ischemic areas on the DWI image are digitally subtracted from the areas of hypoperfusion in the time-delay image, the remaining colored areas on the time-delay map would represent areas of threatened infarction. This digital subtraction technique allows an assessment of continued risk in patients with acute ischemic stroke.

20. Echocardiography
Identify a source of cerebral emboli when ischemic stroke is associated with atrial fibrillation, acute MI, or left-sided endocarditis.
Identify a patent foramen ovale in patients with ischemic stroke and recent or prior thromboembolism.

21. THROMBOLYTIC THERAPY

22. Selection Criteria

23. Time Restriction
The use of thrombolytic therapy in ischemic stroke was prompted by a single study, which showed that a 60-minute infusion of recombinant tissue plasminogen activator (tPA) was associated with improved neurologic recovery (not survival), but only when the drug infusion started within 3 hours after the onset of symptoms.

24. Time Restriction
This 3-hour time restriction has limited the use of thrombolytic therapy in ischemic stroke; i.e., surveys indicate that only 2% of patients with ischemic stroke receive thrombolytic therapy.
EXPANDED TIME LIMIT: 
A more recent clinical study has shown that thrombolytic therapy started between 3 and 4.5 hours after the onset of ischemic stroke also improves neurologic recovery.

25. Time Restriction
Based on these results, the time for initiating thrombolytic therapy has recently been expanded to 4.5 hours after the onset of ischemic stroke.
Why adhere to these time restrictions? Because about 6% of patients who receive thrombolytic therapy for ischemic stroke will suffer from an intracerebral hemorrhage, so evidence of benefit is necessary to justify this therapy.

26. Time of Stroke Onset
The time restriction for thrombolytic therapy makes it imperative to pinpoint the time when the stroke began (i.e., became symptomatic).
This can be difficult, because patients are unable to provide a reliable history and, in many cases, the onset of symptoms is not witnessed (or occurs during sleep).

27. Hypertension
One of the exclusion criteria for thrombolytic therapy is an elevated blood pressure; i.e., a systolic pressure ≥185 mm Hg, or a diastolic pressure ≥110 mm Hg.
If the blood pressure reduction is successful and the patient receives thrombolytic therapy, the blood pressure should be maintained at < 180/105 for the next few days to limit the risk of intracranial hemorrhage.

29. Thrombolytic Regimen
Thrombolytic therapy should be initiated as soon as possible, because earlier initiation is associated with better outcomes. Recombinant tissue plasminogen activator (tPA) is the only thrombolytic agent approved for use in acute stroke.
Dosing Regimen:
The dose of tPA is 0.9 mg/kg, up to a maximum dose of 90 mg. Ten percent of the dose is given IV over 1-2 minutes, and the remainder is infused over 60 minutes. 

30. Thrombolytic Regimen
The infusion should be stopped for any signs of possible intracerebral hemorrhage, such as a deteriorating neurological status, a sudden rise in blood pressure, or a complaint of headache.
After the infusion is stopped, an emergent CT scan (without contrast) should be obtained.
Following successful completion of the thrombolytic regimen, patients are typically admitted to an ICU for 24 hours. 
The administration of any anticoagulant or antiplatelet agent is contraindicated for the first 24 hours after thrombolytic therapy.

31. Antithrombotic Therapy
Heparin
Several studies have failed to show a beneficial effect of heparin anticoagulation in ischemic stroke.
 bleeding and thrombocytopenia 
The only recommended use of heparin in acute stroke is for prevention of thromboembolism.

32. Antithrombotic Therapy
Aspirin
Despite the apparent lack of benefit, aspirin therapy is recommended as a routine measure in ischemic stroke.
The initial dose is 325 mg (oral), which is given 24–48 hours after stroke onset (or after thrombolytic therapy), and the daily maintenance dose is 75–150 mg.
Additional antiplatelet agents are not recommended.

33. PROTECTIVE MEASURES

34. Oxygen Therapy
This practice has no proven benefit, and it neglects the toxic effects of oxygen metabolites (especially the participation of superoxide radicals in reperfusion injury), and the fact that oxygen promotes cerebral vasoconstriction.
Recommend supplemental oxygen only when the arterial O2 saturation falls below 94%.

35. Hypertension
Hypertension is reported in 60–65% of patients with acute stroke, and is attributed to several factors, including activation of the sympathetic nervous system, cerebral edema, and a prior history of hypertension.
Blood pressures usually return to baseline levels in 2–3 days.
The indications for blood pressure reduction include a systolic pressure > 220 mm Hg, a diastolic blood pressure > 120 mm Hg, or a complication of hypertension (e.g., acute MI).

36. Treatment Regimens
Labetalol (a combined α, β-adrenergic receptor antagonist) and nicardipine (a calcium channel blocker) share the ability to decrease blood pressure while preserving cardiac output (and cerebral blood flow).
Labetalol is probably the preferred drug because it does not cause tachycardia, but there are no studies comparing these drugs for blood pressure control in acute stroke.

37. Treatment Regimens
Sodium nitroprusside is recommended for severe hypertension (diastolic BP > 140 mm Hg), but nitroprusside infusions are accompanied by an increase in intracranial pressure, which is not a desirable condition in the patient with ischemic brain injury.

39. Fever
Fever develops within 48 hours in 30% of patients with acute stroke, and the presence of fever is associated with worse clinical outcomes.

40. Source of Fever
Fever typically appears within 48 hours after stroke onset, which suggests a noninfectious origin (e.g., from tissue necrosis or intracerebral blood).
However, some studies have found infections in a majority of patients with stroke-related fever.
Therefore, stroke-related fever should be evaluated as potentially infectious in origin.

41. Antipyresis
There is convincing evidence from animal studies that fever is harmful for ischemic brain tissue, and thus antipyretic therapy is justified for stroke-related fever.
Acetaminophen, and nonsteroidal anti-inflammatory agents (NSAIDS).

42. A FINAL WORD
Where’s the Beef?