Topic Progress:

SO WHO GETS WHAT?

Thrombolysis

WHO'S ELIGIBLE?

Diagnosis of ischemic stroke causing measurable neurological deficit.
Helpful to ask the patient if the deficit is disabling to them – can they carry out all of their normal and enjoyable activities as they could before this event?
Onset less than 4.5 hours (note different exclusion criteria if 3-4.5 hours)

Over 18 years old

Section

ONSET < 3h EXCLUSION CRIT

Absolute NO’s:

The symptoms of stroke should not be suggestive of subarachnoid hemorrhage

No major head trauma in previous 3 months

No prior stroke within previous 3 months

No intracranial or intraspinal surgery in the previous 3 months

No arterial puncture at a non-compressible site or lumbar puncture in the previous 7 days

No history of previous recent intracranial hemorrhage

No history of intracranial neoplasm, aneurysm, or arteriovenous malformation. Small asymptomatic, unsecured intracranial aneurysm is OK to give

Blood pressure not elevated (systolic < 185 mmHg and diastolic < 110 mmHg)

No evidence of active bleeding or acute trauma (fracture) on examination.

Not taking an oral anticoagulant or, if anticoagulant being taken, INR < 1.7 or PT > 15 seconds.

No current use of direct thrombin inhibitors or direct factor Xa inhibitors

aPTT must be in normal range.

Platelet count <100 000 mm3.

Blood glucose concentration < 2.7 mmol/l

CT does not show a multilobar infarction (hypodensity >1/3 cerebral hemisphere)

Relative NO’s

The neurological signs are rapidly improving

The neurological signs are minor and isolated – should be based on whether the patient considers deficit disabling to them – can they carry out all of their normal and enjoyable activities as they could before this event?

Pregnancy

Seizure with postictal residual neurological impairments

Major surgery or major trauma in the previous 14 days

Gastrointestinal or urinary tract hemorrhage in previous 21 days

Myocardial infarction in the previous 3 months

ONSET 3-4.5 h EXCLUSION CRITERIA

The risk-benefit for thrombolysis is even murkier after 3 hours, with ICH risk rising.
So all exclusions for onset <3 hours AND:

Age > 80 years
Any anticoagulant use, regardless of INR
NIHSS > 25
Combined history of prior stroke and diabetes

ONSET 4.5-24H

Beyond 4.5 hours, IV tPA is associated with increased risks and unproven efficacy
ECR may still be appropriate for LVO

HOW TO THROMBOLYSE

IV tenecteplase (0.25mg/kg, maximum of 25mg)
More details here
or
IV alteplase (0.9mg/kg, maximum of 90mg)
More details here

BLOOD PRESSURE CONTROL

BP > 185/110 mmHg

When blood pressure (BP) exceeds 185/110 mmHg

If the patient is a potential thrombolysis candidate, interventions to control BP should be initiated immediately.
Short-acting intravenous and/or titratable IV antihypertensive agents can be used for the treatment of hypertension in the acute setting.

Follow local guidelines, but examples include:

Hydralazine

10 – 20 mg slow IV/IM bolus q4-6 hr PRN, max 40 mg/dose

Labetalol

20-80mg IV bolus q10 min OR 0.5-2 mg/min IV infusion

Clevidipine infusion

1–2 mg/hr (2–4 mL/hr) more here

Metoprolol

1-5 mg IV as slow bolus

Once below 185/110 mmHg, proceed to IV tPA administration.

If BP proves refractory to the above, the risk for intracerebral hemorrhage is considered too high and the patient should not be treated with tPA.
Continue to treat BP to keep less than 220/120 mmHg.

ECR

WHO'S ELIGIBLE?

Over 18 years old

ONSET 0-6 H

Need CTA and CTP
Consider ECR if:
Ischaemic stroke with confirmed LVO on CTA of either:

Internal carotid artery
Middle cerebral artery − M1 segment or proximal M2
Basilar artery

If NIHSS ≥ 5 AND
Pre-morbid modified Rankin Scale (mRS) ≤ 2
Currently, if eligible, thrombolysis is still given while ECR being organised
Patients not meeting the above inclusion criteria but may benefit from intervention may be accepted for ECR after consultation with a capable centre for example:

Patients with low NIHSS but large vessel occlusion may fluctuate clinically and should be reviewed by an ECR capable centre stroke team.
Patients with improving symptoms but large volume of tissue at risk from large vessel occlusion. Such patients may be at significant risk of subsequent deterioration (the risk of deterioration and significant disability in such patients with initially rapidly improving symptoms is probably significantly greater than the peri-procedural risk).
Patients with a higher mRS due to mobility but independent with good quality of life. mRs = 3
Any distal occlusion site outside of the inclusion criteria with a clinically significant deficit.

Evidence

MR CLEAN Trial

ESCAPE 2015
REVASCAT 2015
SWIFT PRIME 2015

ONSET 6-24 H

Late ECR can be considered if significantly disabled (NIHSS ≥ 5), LVO, a small core infarct size and a large salvageable amount of threatened brain.
So:
NIHSS ≥ 5
CTA/MRA with LVO and
CTP/ MR Perfusion with mismatch profile using DAWN or DEFUSE trial criteria in anterior circulation strokes

DEFUSE 3

The DEFUSE 3 trial randomized patients with:
signs and symptoms of anterior circulation stroke with LVO
NIHSS≥6 with
The target mismatch profile was defined as ischemic core volume of <70 ml, and a mismatch ratio of > 1.8 or ≥ 15 ml (ratio of ischemic penumbral tissue volume to infarct volume)
Showed a benefit in functional outcome in favor of ECR (modified Rankin scale 0–2, 44.6% versus 16.7%; RR 2.67; 95% CI 1.60–4.48; P < 0.0001).

DAWN

The DAWN trial used a clinical-imaging mismatch to select patients with anterior circulation strokes due to LVO to select patients for mechanical thrombectomy between 6 and 24 h of LKW time.
It demonstrated an overall benefit in functional outcome at 90 days following endovascular therapy compared to the control group (mRS score 0–2, 49% vs. 13%, adjusted difference, 33%, 95% CI 24–44, with a probability of superiority, > 0.999).
DAWN Summary Video.

ONSET 24-48H

Basilar artery revascularisation may be considered up to 48 hours.

WHAT IS ECR?

TIA’s

As symptoms must have FULLY RESOLVED to diagnose a TIA, this is outside of the algorithm above

WHAT IS A TIA?

Transient ischaemic attacks (TIA’s) do not require thrombolysis or ECR but require other management.

Diagnosis of TIA is based on new onset of focal neurological symptoms that are explainable by a vascular cause (i.e. arterial occlusion of a single or group of arteries adequately explain the patient’s signs and symptoms) and these signs and symptoms resolve within 24 hours (most TIA’s resolve in a much shorter period of time).

If the patient’s symptoms clear by 24 hours but an acute infarct is observed on brain imaging, this is defined as a stroke, not a TIA.
So to diagnose a TIA the symptoms must FULLY RESOLVE

ABCD2 SCORE

The ABCD2 score is an ordinal scale that provides risk prediction of stroke following the TIA.

Based on this risk stratification, some physicians choose to admit high-risk patients and discharge those with low risk, and controversy exists about moderate-risk patients.

It is scored as follows:

ABCD2 0-3 LOW RISK TIA

Can go home

Should start dual anti-platelet agents: aspirin 100 mg daily and clopidogrel 75 mg daily unless contraindications exist

Initiate high intensity statin if not taking one already (moderate intensity statin in patients > 75 years old)

If atrial fibrillation identified, consider full anti-coagulation; calculate CHA₂DS₂-VASc to help guide long term therapy.

Consider longer-term outpatient cardiac monitoring (30 days) if the TIA is embolic and atrial fibrillation is not identified already or if there is no other cause for TIA

Arrange carotid imaging: ultrasound, CTA or MRA

Consider transthoracic echocardiography

Smoking cessation counseling

ABCD2 3-7 HIGH RISK TIA

Admit to telemetry monitored bed

Permissive hypertension (not to exceed 220/120 mmHg), and BP should be gradually lowered over 24-48 hours.

Dual antiplatelet therapy if not contraindicated: clopidogrel (300 mg stat, followed by 75 mg/day) and aspirin 100 mg/day for 21 days followed by clopidogrel 75 mg/day for 90 days

Initiate high intensity statins (e.g. atorvastatin 80 mg daily or rosuvastatin 20 mg daily)

If atrial fibrillation identified, consider full anticoagulation (oral anticoagulant or low molecular weight heparin), calculate CHADS2Vasc and HAS-BLED score to guide long term therapy.

Consider initiating longer-term outpatient cardiac monitoring (30 days) if TIA embolic and atrial fibrillation is not identified already or if there is no other cause for TIA.