For an adult presenting with suspected acute stroke, what is the immediate emergency medication protocol—including non‑contrast computed tomography to differentiate ischemic from hemorrhagic stroke, intravenous tissue plasminogen activator dosing and blood pressure requirements, antiplatelet and statin initiation, criteria for endovascular mechanical thrombectomy, and management of hemorrhagic stroke with blood pressure control and reversal agents?

Acute Stroke Emergency Medication Protocol

Immediate Imaging to Differentiate Stroke Type

All patients with suspected acute stroke must undergo immediate non-contrast CT (NCCT) of the head to exclude intracranial hemorrhage before any reperfusion therapy is initiated. 1, 2, 3

• Complete brain imaging within 30-45 minutes of emergency department arrival to meet quality benchmarks and avoid treatment delays. 4
• NCCT is the primary modality because it is widely accessible, rapidly excludes hemorrhage, and does not delay thrombolysis. 1
• Add CT angiography (CTA) from aortic arch to vertex immediately after NCCT for all patients presenting within 6 hours of symptom onset to identify large vessel occlusion (LVO) and guide endovascular therapy decisions. 1, 3, 4
• MRI with diffusion-weighted imaging (DWI) may be used instead of CT if it does not delay treatment; MRI is more sensitive for detecting acute ischemia and posterior circulation strokes, but accessibility often limits its use in hyperacute settings. 1

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Intravenous Tissue Plasminogen Activator (tPA) Protocol

Dosing and Administration

Administer intravenous alteplase at 0.9 mg/kg (maximum 90 mg total dose) with 10% given as an initial bolus over 1 minute and the remaining 90% infused over 60 minutes. 3, 5, 6

• The standard treatment window is within 4.5 hours of symptom onset (or last known well time), with strongest benefit when given within 3 hours. 3, 5, 6
• Recent evidence from the HOPE trial (2025) demonstrates that alteplase administered 4.5 to 24 hours after onset improves functional independence (40% vs 26% with standard care) in patients with salvageable brain tissue identified by perfusion imaging, though symptomatic intracranial hemorrhage risk increases (3.8% vs 0.5%). 7
• For extended window treatment (4.5-24 hours), use advanced imaging (CT perfusion or MRI perfusion/diffusion) to identify salvageable penumbra before administering alteplase. 4, 7

Blood Pressure Requirements for tPA

Before initiating alteplase, blood pressure must be lowered to and maintained below 185/110 mmHg; after thrombolysis, maintain BP below 180/105 mmHg for 24 hours. 2, 3

• Use labetalol 10 mg IV push (may repeat every 10-20 minutes, maximum 300 mg) or nicardipine infusion starting at 5 mg/hour (titrate by 2.5 mg/hour every 5-15 minutes, maximum 15 mg/hour) to achieve target BP. 2
• Avoid aggressive BP reduction below these thresholds because cerebral perfusion in acute stroke is pressure-dependent and excessive lowering may worsen ischemia. 1, 2

Key Contraindications

• Intracranial hemorrhage on imaging (absolute contraindication). 1, 3
• Blood glucose <50 mg/dL (hypoglycemia mimics stroke and must be corrected immediately). 2, 3
• Recent use of direct oral anticoagulants (DOACs) within 48 hours or INR >1.7 on warfarin. 2
• Platelet count <100,000/mm³. 3
• Frank hypodensity on CT involving more than one-third of middle cerebral artery (MCA) territory is a strong relative contraindication due to hemorrhage risk. 1

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Antiplatelet and Statin Initiation

Antiplatelet Therapy

Do not administer antiplatelet agents within 24 hours of alteplase administration due to increased bleeding risk. 3

• For patients who do not receive thrombolysis, initiate aspirin 160-325 mg orally within 24-48 hours of stroke onset. 3
• Dual antiplatelet therapy (aspirin plus clopidogrel) for 21 days may be considered for minor stroke or high-risk TIA but is not standard in the immediate hyperacute phase. 3

Statin Therapy

Initiate high-intensity statin therapy (e.g., atorvastatin 80 mg daily) within 24-48 hours of ischemic stroke onset for secondary prevention, regardless of baseline cholesterol levels. 3

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Endovascular Mechanical Thrombectomy Criteria

Perform mechanical thrombectomy for patients with large vessel occlusion (LVO) in the anterior circulation (internal carotid artery or proximal middle cerebral artery M1 segment) presenting within 6 hours of symptom onset. 3

• Extend the thrombectomy window to 24 hours for selected patients who meet advanced imaging criteria showing salvageable penumbra on CT perfusion or MRI (mismatch between infarct core and hypoperfused tissue). 2, 3, 4
• Use a "drip-and-ship" approach: administer alteplase at the primary stroke center and immediately transfer to a comprehensive stroke center for thrombectomy when LVO is identified. 2
• Do not delay thrombectomy to observe the effect of alteplase; mechanical thrombectomy remains highly effective even after thrombolysis. 2
• Target door-to-groin puncture time ≤90 minutes at thrombectomy-capable centers. 3

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Management of Hemorrhagic Stroke

Blood Pressure Control

For intracerebral hemorrhage (ICH), lower systolic blood pressure to <140 mmHg within 1 hour of presentation using intravenous agents (labetalol or nicardipine) to reduce hematoma expansion. 3

• Avoid excessive BP reduction below 130 mmHg systolic as it may compromise cerebral perfusion. 3

Reversal Agents for Anticoagulation

For warfarin-associated ICH with INR >1.4, administer intravenous vitamin K 10 mg plus four-factor prothrombin complex concentrate (PCC) 25-50 units/kg to achieve rapid INR reversal. 3

• For DOAC-associated ICH, use specific reversal agents: idarucizumab 5 g IV for dabigatran; andexanet alfa for factor Xa inhibitors (apixaban, rivaroxaban). 3
• Fresh frozen plasma (FFP) is inferior to PCC for warfarin reversal and should not be first-line. 3

Seizure Management

Treat acute seizures at stroke onset with short-acting benzodiazepines (lorazepam 2-4 mg IV) if seizures are not self-limited. 1, 3

• Do not use prophylactic anticonvulsants; there is no evidence of benefit and potential harm to neural recovery. 1, 3

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Critical Time Targets and Common Pitfalls

Time Targets

• Door-to-imaging time: ≤25 minutes. 2
• Door-to-needle time for alteplase: ≤30 minutes (90th percentile ≤60 minutes). 2, 3
• Each 15-minute reduction in door-to-needle time decreases in-hospital mortality by 5%. 2

Common Pitfalls to Avoid

• Never delay transfer to obtain imaging at a non-CT facility; rapid transport to a stroke-capable center supersedes any on-site intervention. 2
• Do not withhold treatment for "mild" or improving symptoms; large vessel occlusions can present with fluctuating deficits and still benefit from reperfusion. 2
• Do not assume patients beyond 4.5 hours are ineligible; endovascular therapy may be offered up to 24 hours with appropriate imaging selection. 2, 7
• Avoid routine supplemental oxygen; only provide oxygen if saturation is <94%. 2, 3
• Do not administer dextrose-containing IV fluids unless hypoglycemia is documented; use normal saline for volume resuscitation. 2