Acute Stroke Protocol: A Contemporary Review 

Dr Neeraj Manikath , claude.ai

Abstract

Acute ischemic stroke remains a leading cause of mortality and long-term disability worldwide, demanding rapid, systematic intervention. This review synthesizes current evidence-based protocols for acute stroke management, emphasizing time-critical interventions, patient selection criteria, and practical clinical pearls for internists. We explore the evolution from "time is brain" to tissue-based selection, discuss contemporary reperfusion strategies, and highlight common pitfalls that can compromise patient outcomes.

Introduction

Stroke affects approximately 795,000 Americans annually, with ischemic stroke comprising 87% of cases.¹ The exponential growth in therapeutic options over the past two decades has transformed stroke from a nihilistic diagnosis to a treatable emergency. However, this progress demands that internists maintain current knowledge of rapidly evolving protocols. The window for intervention has expanded significantly—from 3 hours to potentially 24 hours in selected patients—fundamentally changing stroke triage and management.²

Prehospital Recognition and Triage

Pearl #1: The FAST-ED Protocol

While the traditional FAST (Face, Arms, Speech, Time) mnemonic remains valuable, the FAST-ED protocol adds "Eyes" (gaze deviation or visual field defect) and "Deny" (neglect), improving sensitivity for large vessel occlusion (LVO) from 33% to 60%.³ LVO identification in the prehospital setting enables direct routing to thrombectomy-capable centers, reducing time to intervention.

Hack: Leveraging EMS for Door-to-Needle Times

Prehospital notification allows emergency departments to activate stroke teams before patient arrival. Studies demonstrate that advance notification reduces door-to-imaging time by 10-15 minutes and door-to-needle time by 20 minutes.⁴ Ensure your institution has robust communication protocols with emergency medical services.

Initial Emergency Department Evaluation

The First 10 Minutes

Time-critical initial assessment requires parallel processing. The mnemonic "ABC-STAT" captures essential elements:

• Airway protection and oxygen if hypoxic (SpO₂ <94%)
• Blood pressure measurement (do not treat initially unless >220/120 mmHg)
• CT head without contrast immediately
• Serum glucose (treat if <60 mg/dL)
• Time of symptom onset or last known well (LKW)
• Antiplatelet history and recent anticoagulant use
• Troponin and ECG (atrial fibrillation identification)

Oyster #1: The "Wake-Up Stroke" Dilemma

Approximately 25% of strokes occur during sleep.⁵ Previously, these patients were automatically excluded from thrombolysis due to unknown onset time. The WAKE-UP trial revolutionized this paradigm by using MRI-based tissue selection (DWI-FLAIR mismatch) to identify patients likely within the treatment window, demonstrating efficacy up to 4.5 hours from LKW.⁶ Similarly, perfusion imaging extends treatment windows in both wake-up strokes and late presenters.

Neuroimaging: Beyond Basic CT

CT Head: What Internists Must Recognize

Non-contrast CT primarily excludes hemorrhage but provides additional crucial information:

• Hyperdense MCA sign: Thrombus visualization indicating LVO
• Loss of insular ribbon: Early ischemic change
• Alberta Stroke Program Early CT Score (ASPECTS): Quantifies early ischemic changes; scores ≥6 predict better outcomes with intervention⁷

Pearl #2: CT Angiography is Standard of Care

CT angiography (CTA) should be performed immediately in all stroke patients without contraindication. CTA identifies LVO, determines eligibility for thrombectomy, and reveals arterial dissection or other vascular pathology. The additional 3-5 minutes required for CTA should not delay thrombolysis administration.⁸

Advanced Imaging Selection Criteria

CT Perfusion and MRI Diffusion-Weighted Imaging

The DAWN and DEFUSE-3 trials established perfusion imaging's role in patient selection for late-window thrombectomy (6-24 hours).⁹'¹⁰ These studies utilized the concept of "clinical-core mismatch"—identifying patients with salvageable tissue despite delayed presentation. Key principles:

• Large penumbra relative to core infarct predicts benefit
• Automated software (RAPID, Vitrea) standardizes assessment
• Not required for patients presenting within 6 hours with LVO

Intravenous Thrombolysis: Current Evidence

Alteplase Administration: The Gold Standard

Intravenous tissue plasminogen activator (IV tPA) remains the cornerstone of acute stroke treatment for patients meeting criteria within 4.5 hours of onset. Standard dosing: 0.9 mg/kg (maximum 90 mg), with 10% given as bolus and 90% infused over 60 minutes.¹¹

Updated Inclusion Criteria:

• Symptom onset <4.5 hours (or DWI-FLAIR mismatch)
• Age >18 years (no upper age limit)
• Measurable neurological deficit
• CT excludes hemorrhage

Hack: Relative Contraindications are Increasingly Relative

Modern evidence has relaxed several traditional contraindications:

• Minor stroke (NIHSS <6): Previously controversial, the PRISMS trial showed no benefit but safety is established¹²
• Prior stroke and diabetes: No longer absolute contraindication beyond 3 hours
• Recent surgery: Case-by-case assessment; many patients with recent procedures can receive tPA safely¹³
• Anticoagulation with INR <1.7: Now acceptable

Pearl #3: Blood Pressure Management During Thrombolysis

Maintain BP <185/110 mmHg before tPA and <180/105 mmHg for 24 hours post-thrombolysis. Use short-acting agents (labetalol, nicardipine) allowing rapid titration. Avoid precipitous BP reduction, which may worsen penumbral ischemia.

The Tenecteplase Revolution

Tenecteplase (TNK), a genetically modified tPA variant, offers advantages over alteplase: single bolus administration, greater fibrin specificity, and longer half-life. Multiple trials including NOR-TEST and EXTEND-IA TNK demonstrated non-inferiority to alteplase, with some evidence suggesting superiority in LVO cases.¹⁴ Dosing: 0.25 mg/kg (maximum 25 mg) IV bolus. While not yet FDA-approved for stroke, many institutions have adopted TNK as standard of care.

Hack: TNK Facilitates Drip-and-Ship

For community hospitals, TNK's single bolus administration simplifies transfer to thrombectomy centers, avoiding interruption of alteplase infusion during transport.

Mechanical Thrombectomy: The Game-Changer

Five landmark trials in 2015 (MR CLEAN, ESCAPE, EXTEND-IA, SWIFT PRIME, REVASCAT) established mechanical thrombectomy's dramatic efficacy for anterior circulation LVO.¹⁵ Number needed to treat: 2.6 for improved functional outcome—among the most effective interventions in medicine.

Patient Selection for Thrombectomy

Early Window (0-6 hours):

• Anterior circulation LVO (ICA, M1, proximal M2)
• ASPECTS ≥6
• Pre-stroke modified Rankin Scale (mRS) 0-1
• No advanced imaging required

Late Window (6-24 hours):

• Requires perfusion imaging or MRI
• DAWN criteria: Clinical-core mismatch based on age, NIHSS, and infarct volume⁹
• DEFUSE-3 criteria: Core <70 mL, mismatch ratio ≥1.8¹⁰

Pearl #4: Basilar Artery Occlusion

Basilar occlusions carry >80% mortality without intervention. Recent trials (BASICS, BEST, ATTENTION) demonstrate benefit for thrombectomy up to 24 hours in posterior circulation strokes.¹⁶ Maintain high clinical suspicion with altered consciousness, quadriplegia, or bilateral deficits.

Post-Thrombolysis Management

The Critical First 24 Hours

Oyster #2: The Antiplatelet Timing Paradox

Do not administer antiplatelet agents or anticoagulation for 24 hours post-thrombolysis due to hemorrhage risk. Perform follow-up CT at 24 hours before initiating antiplatelet therapy. However, in non-thrombolyzed patients with minor stroke, dual antiplatelet therapy (aspirin + clopidogrel) initiated within 24 hours reduces recurrent stroke risk (POINT, CHANCE trials).¹⁷'¹⁸

Blood Pressure Management: The Pendulum Swings

Post-stroke BP management remains nuanced:

• After thrombolysis: Maintain <180/105 mmHg
• Without reperfusion: Permissive hypertension (<220/120 mmHg) for first 48-72 hours preserves collateral flow
• After thrombectomy with successful reperfusion: Target <180/105 mmHg
• After thrombectomy with incomplete reperfusion: More permissive approach

The ENCHANTED trial suggested intensive BP lowering may worsen outcomes, reinforcing cautious approach.¹⁹

Secondary Prevention: Preventing the Next Stroke

Rapid Etiologic Workup

Pearl #5: The 1-3-6-12 Rule

• 1 day: Transthoracic echocardiogram, carotid imaging
• 3 days: Extended cardiac monitoring initiated (minimum 24 hours)
• 6 days: Dyslipidemia assessment, diabetes screening
• 12 days: Consider transesophageal echocardiogram if cryptogenic

High-Intensity Statin Therapy

Regardless of baseline LDL, initiate high-intensity statin (atorvastatin 80 mg or rosuvastatin 40 mg) before discharge. SPARCL trial demonstrated 16% relative risk reduction with atorvastatin 80 mg.²⁰ Target LDL <70 mg/dL; consider adding ezetimibe if needed.

Hack: The FAST-MAG Concept

While the FAST-MAG trial of prehospital magnesium was negative, the infrastructure it established demonstrates feasibility of ultra-early intervention. Some systems now administer TNK in the ambulance for patients meeting strict criteria—potentially the future of stroke care.

Common Pitfalls and How to Avoid Them

1. Overcorrecting blood pressure: Aggressive BP reduction worsens outcomes
2. Delaying treatment for "minor" symptoms: Deficits may progress; consider benefits
3. Missing posterior circulation strokes: Atypical presentations (vertigo, diplopia) require high suspicion
4. Inadequate cardiac monitoring: 30-day monitoring detects 5-fold more atrial fibrillation than 24-hour Holter²¹
5. Forgetting rehabilitation: Early mobilization within 24 hours improves outcomes (AVERT trial caveat: avoid very early, intensive mobilization)²²

Emerging Therapies and Future Directions

Neuroprotection trials continue despite historical failures. NA-1 (nerinetide) showed promise in specific subgroups. Combination low-dose thrombolysis with thrombectomy is under investigation. Stroke unit care with organized, multidisciplinary approach reduces mortality by 15% independent of specific interventions.²³

Conclusion

Acute stroke management exemplifies evidence-based medicine's power to transform outcomes. Internists must embrace the paradigm shift from rigid time windows to individualized tissue-based selection. Success requires institutional commitment to protocol adherence, rapid imaging acquisition, and seamless coordination between emergency medicine, neurology, radiology, and neurosurgery. Every minute saved preserves 1.9 million neurons—truly, time is brain.

References

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Key Takeaway: Modern stroke care demands aggressive, time-sensitive intervention guided by advanced imaging. Internists must champion protocol adherence while recognizing that individualized tissue-based selection has expanded therapeutic windows dramatically. Every stroke patient deserves consideration for reperfusion therapy—when in doubt, consult stroke neurology emergently.