CHAPTER 407 ISCHEMIC CEREBROVASCULAR DISEASE
TABLE 4077 ADMINISTRATION OF rtPA FOR ACUTE
ISCHEMIC STROKE
Infuse 0.9 mg/kg (maximum dose 90 mg) over 60 minutes, with 10% of the dose
given as a bolus over 1 minute.
Admit the patient to an intensive care or stroke unit for monitoring.
If the patient develops severe headache, acute hypertension, nausea, or vomiting or
has a worsening neurological examination, discontinue the infusion (if IV rtPA is
being administered) and obtain emergent CT scan.
Measure blood pressure and perform neurological assessments every 15 minutes
during and after IV rtPA infusion for 2 hours, then every 30 minutes for 6 hours,
then hourly until 24 hours after IV rtPA treatment.
Increase the frequency of blood pressure measurements if systolic blood pressure is
>180 mm Hg or if diastolic blood pressure is >105 mm Hg; administer
antihypertensive medications to maintain blood pressure at or below these levels
(Table 407-10).
Delay placement of nasogastric tubes, indwelling bladder catheters, or intra- arterial
pressure catheters if the patient can be safely managed without them.
Obtain a follow-up CT or MRI scan at 24 hours after IV rtPA before starting
anticoagulants or antiplatelet agents.
CT = computed tomography; IV = intravenous; MRI = magnetic resonance imaging; rtPA =
recombinant tissue plasminogen activator.
From Jauch EC, Saver JL, Adams HP Jr, et al. Guidelines for the early management of patients with
acute ischemic stroke: a guideline for healthcare professionals from the American Heart
Association/American Stroke Association. Stroke. 2013;44:870-947.
beyond 4.5 hours. Registry studies support a benefit in routine clinical practice
similar to that in randomized trials.6 As a result, current guidelines recommend
that treatment with intravenous rtPA (Food and Drug Administration approved
up to 3 hours after symptom onset) not be given if more than 4.5 hours have
elapsed since the onset of symptoms. Treatment with rtPA is efficacious and
safe among patients who are chronically treated with warfarin, provided their
INR is 1.7 or lower, and is contraindicated with an INR higher than 1.7. A2 Treat-
ment increases the risk of intracranial hemorrhage, but the overall benefit
includes these adverse events, which do not significantly increase in frequency
during the 4.5-hour treatment window. Some patients have absolute exclusion
criteria against treatment with intravenous rtPA (Table 407-8), with additional
relative contraindications for treatment between 3 and 4.5 hours (Table 407-9).
In patients without contraindications, treatment should begin as soon as pos-
sible in either treatment window.
Endovascular Therapy
Although strokes caused by large proximal occlusions tend to benefit less
from treatment with intravenous rtPA compared with more distal or small-
vessel obstructions, no randomized trials show additional benefit of infusing
rtPA directly into the thrombus or of other endovascular treatments compared
with intravenous rtPA alone, even though several devices are Food and Drug
Administration approved to remove clots from brain blood vessels. As a result,
current guidelines recommend treatment with intravenous rtPA even if intra-
arterial treatments are available. Endovascular therapy can be considered in
selected patients who cannot be treated with intravenous rtPA, such as
patients who had a recent surgical procedure and who present up to 6 hours
after a middle cerebral artery occlusion and perhaps longer after basilar artery
occlusion.
Other Treatments
Regardless of whether the patient received intravenous rtPA or endovascu-
lar therapy, care in a comprehensive specialized stroke unit that incorporates
rehabilitation is associated with better patient outcomes. Urgent anticoagula-
tion to prevent recurrent stroke, to prevent worsening, or to improve func-
tional outcome of patients with acute ischemic stroke is not recommended.
Aspirin should not be started within 24 hours of treatment with intravenous
rtPA, but aspirin should be started at 325 mg daily within 24 to 48 hours after
the onset of stroke. A3 Hemicraniectomy can increase survival in patients with
extensive middle cerebral artery strokes, but most survivors will require assis-
tance with their body needs. A4
Antihypertensive medications to reduce blood pressure acutely by 10 to
25% in the first 24 hours with a goal of blood pressure to below 140/90 mm Hg
by 1 week does not improve outcomes compared with discontinuation of all
antihypertensive medications. A5 Current guidelines recommend that antihy-
pertensive medications not be given unless the blood pressure rises to more
than 220/120 mm Hg or higher in the absence of other indications. An excep-
tion is that blood pressure can be lowered in patients who are otherwise
candidates for intravenous rtPA with a goal of maintaining blood pressures
below 180/105 mm Hg after treatment (Fig. 407-5).
Several potential complications of acute stroke can often be avoided.
Patients with stroke in any vascular distribution are at risk of aspiration
2441
TABLE 4078 INCLUSION AND EXCLUSION
CHARACTERISTICS OF PATIENTS WITH
ISCHEMIC STROKE WHO COULD BE TREATED
WITH IV rtPA WITHIN 3 HOURS FROM
SYMPTOM ONSET
INCLUSION CRITERIA
Diagnosis of ischemic stroke causing measurable neurological deficit
Onset of symptoms <3 hours before beginning treatment
Aged ≥18 years
EXCLUSION CRITERIA
Significant head trauma or prior stroke in previous 3 months
Symptoms suggest subarachnoid hemorrhage
Arterial puncture at noncompressible site in previous 7 days
History of previous intracranial hemorrhage
Intracranial neoplasm, arteriovenous malformation, or aneurysm
Recent intracranial or intraspinal surgery
Elevated blood pressure (systolic >185 mm Hg or diastolic >110 mm Hg)
Active internal bleeding
Acute bleeding diathesis, including but not limited to
Platelet count <100,000/mm3
Heparin received within 48 hours, resulting in aPTT greater than the upper limit
of normal
Current use of anticoagulant with INR >1.7 or PT >15 seconds
Current use of direct thrombin inhibitors or direct factor Xa inhibitors with
elevated sensitive laboratory tests (such as aPTT, INR, platelet count, and
ECT; TT; or appropriate factor Xa activity assays)
Blood glucose concentration <50 mg/dL (2.7 mmol/L)
CT demonstrates multilobar infarction (hypodensity > 1 3 cerebral hemisphere)
RELATIVE EXCLUSION CRITERIA
Recent experience suggests that under some circumstances—with careful
consideration and weighting of risk to benefit—patients may receive fibrinolytic
therapy despite 1 or more relative contraindications. Consider risk to benefit of IV
rtPA administration carefully if any of these relative contraindications are present:
Only minor or rapidly improving stroke symptoms (clearing spontaneously)
Pregnancy
Seizure at onset with postictal residual neurological impairments
Major surgery or serious trauma within previous 14 days
Recent gastrointestinal or urinary tract hemorrhage (within previous 21 days)
Recent acute myocardial infarction (within previous 3 months)
NOTES:
• The checklist includes some FDA-approved indications and contraindications for
administration of IV rtPA for acute ischemic stroke. Recent guideline revisions have
modified the original FDA-approved indications. A physician with expertise in
acute stroke care may modify this list.
• Onset time is defined as either the witnessed onset of symptoms or the time last
known normal if symptom onset was not witnessed.
• In patients without recent use of oral anticoagulants or heparin, treatment with IV
rtPA can be initiated before availability of coagulation test results but should be
discontinued if INR is >1.7 or PT is abnormally elevated by local laboratory
standards.
• In patients without history of thrombocytopenia, treatment with IV rtPA can be
initiated before availability of platelet count but should be discontinued if platelet
count is <100,000/mm3.
aPTT = activated partial thromboplastin time; CT = computed tomography; ECT = ecarin clotting
time; FDA = Food and Drug Administration; INR = international normalized ratio; IV =
intravenous; PT = partial thromboplastin time; rtPA = recombinant tissue plasminogen activator;
TT = thrombin time.
From Jauch EC, Saver JL, Adams HP Jr, et al. Guidelines for the early management of patients with
acute ischemic stroke: a guideline for healthcare professionals from the American Heart
Association/American Stroke Association. Stroke. 2013;44:870-947.
pneumonia (Chapter 97). Stroke patients should not receive oral medications
or nutrition until their ability to swallow safely has been assessed. Urinary tract
infections (Chapter 284) are a potential complication; the routine placement
of indwelling bladder catheters should be avoided, and patients who require
an indwelling bladder catheter should have it removed as soon as feasible. Any
infectious complications should be treated aggressively, and antipyretics
should be used to maintain euthermia because fever is associated with more
ischemic injury and poorer outcomes. Immobilized patients should receive
deep venous thrombosis prophylaxis with subcutaneous unfractionated
heparin or low-molecular-weight heparin (see Table 38-2) if it is not contrain-
dicated, with mechanical intermittent pneumatic compression if anticoagula-
tion is contraindicated,A6 or with both.