Stroke (Acute Management)

I. Initial assessment/management of a patient with acute stroke

On history and physical, main goal is to quickly assess is this a stroke vs other causes of neuro deficit or altered mental status; if stroke, could this be a bleed (subarachnoid or intracranial) – i.e., looking for headache and vomiting on history, abducens nerve palsy for signs of elevated ICP, cushing’s reflex on vitals, etc.
ABC’s of course are essential as these patients often have compromised airway and breathing, especially with aspiration risk.
Key is to get the patient in for a stat noncontrast head CT to r/o a bleed. Other important labs include CBC, chemistries, coags, troponins, and EKG.
Head positioning depends on whether or not the patient is at risk for elevated intracranial pressure or aspiration. If yes, put their head up at a 30 degree angle. If not, lay them flat for a maximum of 24-48 hours, to maximize cerebral perfusion pressure.
Blood pressure control is tricky and depends on if the stroke is ischemic or a bleed: 1) Ischemic – generally, the rule is for permissive HTN to allow for adequate Cerebral Perfusion Pressure. Do not treat unless the SBP is > 220 or DBP > 120, UNLESS the patient has active cardiac ischemic, heart failure, aortic dissection, hypertensive encephalopathy, or acute renal failure. If thrombolysis is considered (see below), the goal BP is < 185/110. 2) ICH/SAH – generally, more aggressive blood pressure control is indicated, in order to prevent worsening bleed.
Glycemic control and maintenance of normothermia (in febrile patients) is backed by some evidence showing that hyperglycemia and fever is associated with worsened neurological outcomes.
Acute Therapy for ischemic CVA involves consideration of thrombolysis, as well as antiplatelet therapy.

II. Review Indications and Contraindications for Thrombolysis for Acute Stroke
Indication = Ischemic CVA causing measurable neurological deficit(s) with the onset of symptoms less than 4.5 hours.

Note that the timeframe for tPA has been expanded from 3 to 4.5 hours in the 2009 AHA/ASA Guidelines. This is a result of the ECASS III trial (see below).

Contraindications: Basically, can think of the contraindications in terms of 3 categories: History, Clinical Signs, and Labs.
A. History:

CVA or head trauma within the past 3 months
Prior history of intracranial hemorrhage (any)
Major surgery within 14 days
GI/GU bleed within 21 days
MI within the past 3 months
Recent arterial puncture within 7 days (at a noncompressible site)

B. Clinical:

Resolving CVA symptoms, or minor/isolated symptoms
Hemorrhage on CT scan, or multilobar infarct >33% of hemisphere
Seizure at the onset of CVA
Severe hypertension with BP persistently > 185/110
Acute bleeding or trauma
For 3-4.5 hour window, severe stroke with NIHSS >25

C. Lab:

Platelets < 100
INR > 1.7 or elevated PTT
Glucose < 50

III. Review of the major trials behind tPA effectiveness
1. NINDS (NEJM 1995) – RCT of 624 pts, compared IV alteplase vs placebo for patients with ischemic CVA presenting within 3 hours. At 3 months, significant improvement in complete or near-complete recovery (38% vs 21%). No significant difference in mortality despite 10x higher rates of symptomatic intracranial hemorrhage. Severe systemic hemorrhage occurred in <1% of patients. The greatest benefit was seen in patients who received tpa within 90 minutes.
This was the original trial that established efficacy of thrombolysis within a 3 hour time frame for ischemic stroke.

2. ECASS 1 and 2 (JAMA 1995, Lancet 1998) – large RCTs in Europe that compared tPA vs placebo in patients up to 6 hours. Basically, no benefit was seen in terms of neurological outcomes at 90 days.
These were the trials that attempted to extend the timeframe to 6 hours but failed to show benefit.

3. ECASS 3 (NEJM 2008) – RCT of 821 patients with acute ischemic CVA presenting from 3 to 4.5 hours after symptom onset. In addition to the exclusion criteria in NINDS, they also excluded patients > 80 yo, severe CVA with NIHSS > 25, patients on anticoagulants, and those with a combination of prior CVA and diabetes. A mild benefit was seen for neurological outcomes at 3 months (52% vs 45%), no change in mortality, and increase in symptomatic intracranial hemorrhage (2.2% vs 0.2%).
Third time was the charm for the ECASS investigators - this was the trial that expanded the timeframe from 3 to 4.5 hours in the 2009 AHA/ASA guidelines.
Lastly, a metanalysis published in Lancet 2010 pooled the data from NINDS, ECASS 1-3, and others (ATLANTIS, EPITHET) which basically showed that the sooner tPA is administered, the better the outcomes ("Time is Brain"). For example, in patients given tPA within 90 minutes of symptom onset, the Number Needed to Treat to improve outcomes was 4.5, vs those presenting from 181 to 270 minutes, the NNT is 14. Patients presenting after 4.5 hours had increased mortality with tPA.

IV. Review administration of tPA

tPA is dosed 0.9 mg/kg of actual body weight (maximum 90 mg), with 10% given as an IV bolus over 10 minutes, and the remainder over 1 hour. The patient’s should be closely monitored for the next 24 hours.
Strict BP control to <185/105 is required for 24 hours.
Invasive procedures should be avoided for 24 hours.
One thing to remember, if you give tPA for ischemic stroke, you should hold on further antiplatelet/anticoagulants for at least 24 hours, including aspirin. That is, Aspirin should not be started until 24-48 hours after tPA.

(Chanu Rhee MD, 5/6/11)