What is the protocol for thrombolysis in the Emergency Department (ED)?

Thrombolysis Protocol for Acute Ischemic Stroke in the Emergency Department

Administer intravenous alteplase (tPA) 0.9 mg/kg (maximum 90 mg) with 10% as a bolus over 1 minute and the remainder over 60 minutes to eligible patients with acute ischemic stroke within 4.5 hours of symptom onset, targeting a door-to-needle time of 30 minutes (median) with 90th percentile of 60 minutes. 1

Time-Critical Patient Selection

Within 3 Hours of Symptom Onset

• Inclusion criteria: Acute ischemic stroke with clearly defined time of onset, measurable deficit on NIH Stroke Scale, baseline CT scan showing no hemorrhage 1
• Exclusion criteria: Current intracranial hemorrhage, subarachnoid hemorrhage, active internal bleeding, recent stroke or serious head injury within 3 months, intracranial surgery within 3 months, intracranial conditions that may increase bleeding risk (neoplasms, arteriovenous malformations, aneurysms), bleeding diathesis, severe uncontrolled hypertension (systolic >185 mmHg or diastolic >100 mmHg) 1, 2
• Benefit: 34% reduction in death or dependency (OR 0.66,95% CI 0.56-0.79) without increased mortality 1

Between 3-4.5 Hours of Symptom Onset

• Additional exclusion criteria beyond NINDS: Age >80 years, severe stroke (NIHSS >25), combination of previous stroke and diabetes mellitus, any oral anticoagulant use regardless of INR 1
• Benefit: Reduced death or dependency (OR 0.84) but less robust than <3 hour window 1

Rapid ED Workflow Algorithm

Phase 1: Prehospital (EMS)

• Prehospital notification to ED stroke team with patient-specific information including symptom onset time, current deficits, and estimated arrival time 1
• High priority transportation and triage 1

Phase 2: Emergency Department (Target: Door-to-Needle ≤30 minutes median)

1. Immediate triage using validated stroke screening tool 1
2. Urgent CT brain (as soon as possible, certainly <24 hours) to exclude hemorrhage and stroke mimics 1
3. Vascular imaging with CTA ± CT perfusion for all acute stroke patients within treatment windows 1
4. Routine investigations: Full blood count, electrolytes, renal function, glucose, ECG 1
5. Stroke specialist review of diagnosis and imaging 1

Dosing and Administration Protocol

Standard dose: 0.9 mg/kg (maximum 90 mg total dose) 2

• Bolus: 10% of total dose (0.09 mg/kg) administered over 1 minute 2
• Infusion: Remaining 90% administered over 60 minutes 2

Critical administration notes:

• Intravenous route only 2
• Do not add any other medication to infusion solutions 2
• Use within 8 hours of reconstitution 2
• Avoid intramuscular injections and trauma during infusion 2

Blood Pressure Management During Treatment

Pre-treatment: Systolic BP must be ≤185 mmHg and diastolic BP ≤100 mmHg before initiating tPA 1

During and post-treatment: Maintain systolic BP ≤180 mmHg and diastolic BP ≤105 mmHg 3

Post-Thrombolysis Monitoring Protocol

Neurological Assessment Schedule

• Every 15 minutes during tPA infusion 3
• Every 30 minutes for 6 hours post-treatment 3
• Hourly until 24 hours after treatment 3

Blood Pressure Monitoring Schedule

• Every 15 minutes for first 2 hours 3
• Every 30 minutes for next 6 hours 3
• Hourly until 24 hours after treatment 3

Critical Warning Signs

Immediately discontinue tPA and obtain emergency CT if:

• Severe headache develops 3
• Acute hypertension occurs 3
• Nausea or vomiting 3
• Worsening neurological examination 3

Medication Restrictions

• Delay anticoagulants and antiplatelet agents for 24 hours after tPA administration 3
• Obtain follow-up CT at 24 hours before starting anticoagulants or antiplatelet agents 3
• Delay placement of nasogastric tubes, indwelling bladder catheters, or intra-arterial pressure catheters 3
• Do not routinely administer tPA to patients on direct oral anticoagulants (DOACs) 1

Management of Symptomatic Intracranial Hemorrhage

Risk: Approximately 5-8% of patients develop symptomatic intracranial hemorrhage 1

If hemorrhage suspected:

1. Immediately discontinue remaining tPA infusion 3
2. Obtain emergent non-contrast CT scan 3
3. Consider cryoprecipitate to restore fibrinogen levels 3
4. Consider surgical hematoma evacuation based on size, location, and patient condition 3

Special Populations

Patients Over 80 Years

• Benefit equally to those under 80 years, particularly if treated within 3 hours 1
• However, age >80 is an exclusion criterion for 3-4.5 hour window 1

Wake-Up Stroke

• Treatment decisions should be made in consultation with stroke specialists 4
• Requires advanced neuroimaging (MRI with DWI/FLAIR or CT perfusion) for proper patient selection 4

Hospital Inpatients

• Rapidly evaluate by specialist team and provide access to thrombolysis if eligible 1

Common Pitfalls to Avoid

• Failure to maintain strict blood pressure control increases hemorrhagic transformation risk 3
• Premature anticoagulant/antiplatelet administration before 24-hour CT scan 3
• Inadequate neurological assessment frequency particularly in first 6 hours 3
• Delayed recognition of symptomatic intracranial hemorrhage 3
• Protocol violations related to time criteria, blood pressure monitoring, or antithrombotic administration within 24 hours are associated with higher symptomatic hemorrhage rates and mortality 1

Consent Considerations

Intravenous thrombolysis is considered standard of care for acute stroke treatment; routine procedures for emergency consent apply 1