tPA Dose for Ischemic Stroke Calculator

Why use it

Alteplase dosing errors in acute stroke are among the most dangerous medication errors in emergency medicine — overdose increases intracranial hemorrhage risk, while underdose reduces efficacy. Weight-based calculations under time pressure in an emergency setting are inherently error-prone. This calculator eliminates manual calculation, ensures the 90 mg cap is applied, and provides ready-to-use bolus and infusion volumes in mL for bedside nursing administration.

About

Intravenous alteplase (recombinant tissue plasminogen activator, rt-PA) is the only FDA- and EMA-approved thrombolytic agent for acute ischemic stroke. The standard dose regimen was established by the NINDS rt-PA Stroke Trial (1995): 0.9 mg/kg, with a maximum total dose of 90 mg, administered as a 10% bolus over 1 minute followed by the remaining 90% as an intravenous infusion over 60 minutes. This weight-based calculation ensures appropriate thrombolytic exposure while the 90 mg cap limits hemorrhagic risk in heavier patients. The treatment window has evolved from the original 3 hours (NINDS trial) to 4.5 hours (ECASS-3 trial, 2008) in selected patients meeting additional eligibility criteria. This calculator computes the total alteplase dose, bolus volume, and infusion volume, eliminating weight-based dosing errors — a high-risk calculation known to cause 10% overdose errors when performed manually under time pressure in emergency settings. Alteplase for stroke comes as a 100 mg vial reconstituted with 100 mL sterile water (concentration = 1 mg/mL), simplifying the volume calculation (dose in mg = volume in mL).

When to use

• Any adult with acute ischemic stroke confirmed on CT/MRI brain (no hemorrhage) being considered for IV thrombolysis within the treatment window
• Patient weight must be obtained — estimate or measure; for morbidly obese patients, the 90 mg cap applies at approximately 100 kg
• Only after checking absolute and relative contraindications to thrombolysis
• Within 3 hours of symptom onset (standard window): most patients meeting NINDS eligibility criteria
• Within 3–4.5 hours (extended window): patients meeting ECASS-3 criteria — no prior stroke + diabetes, age ≤80, NIHSS ≤25, no anticoagulant use, no extensive early ischemic changes on CT
• NOT for hemorrhagic stroke — CT or MRI must exclude intracranial hemorrhage before administration
• NOT validated for use in pediatric patients — consult pediatric neurology

Formula

Pearls & pitfalls

• The 90 mg maximum cap applies at a weight of ~100 kg (90/0.9 = 100 kg). All patients ≥100 kg receive the same dose: 9 mg bolus + 81 mg infusion, regardless of actual weight.
• The alteplase 100 mg vial reconstituted with 100 mL sterile water gives exactly 1 mg/mL — dose in mg equals volume in mL. This greatly simplifies bedside calculation and administration.
• NINDS trial (1995): 0–3 hour window; 13% absolute reduction in disability at 3 months; 6% absolute increase in intracranial hemorrhage (10.9% vs 4.6%), most small and clinically silent; no mortality difference.
• ECASS-3 trial (2008): extended to 4.5 hours in patients aged ≤80, no prior stroke + diabetes, NIHSS ≤25, no anticoagulant use, no >1/3 MCA territory involvement — benefit persists but is smaller than in the 3-hour window.
• Blood pressure must be controlled to <185/110 mmHg BEFORE initiating tPA, and maintained <180/105 mmHg for 24 hours after. IV labetalol (10–20 mg over 1–2 min) or nicardipine infusion (5 mg/hr, titrate) are first-line agents.
• Symptomatic intracranial hemorrhage (sICH) occurs in approximately 6% of treated patients. Risk factors: high NIHSS (>25), advanced age, hyperglycemia (glucose >200 mg/dL), early CT ischemic changes, prior antiplatelet use, severe hypertension.
• If neurological deterioration occurs during infusion: STOP tPA immediately, obtain emergency CT, order fibrinogen level and CBC. If sICH confirmed: cryoprecipitate (10 units IV) to replenish fibrinogen; neurosurgical consultation for clot evacuation if cerebellar or accessible location.
• Tenecteplase (TNK-tPA) 0.25 mg/kg (max 25 mg) single IV bolus is emerging as a non-inferior alternative to alteplase for acute ischemic stroke and may be preferred for ease of administration (ATTEST-2, AcT trials, 2022–2023).

Next steps

After calculating the dose: (1) Reconstitute alteplase 100 mg vial with 100 mL sterile water — final concentration 1 mg/mL; (2) Draw up bolus volume (mL = 10% of total dose mg) into a syringe; administer IV over 1 minute; (3) Infuse remaining volume (mL = 90% of total dose mg) via IV pump over 60 minutes; (4) NO heparin, antiplatelet, or anticoagulant agents for 24 hours after tPA; (5) Admit to stroke unit with continuous cardiac and neurological monitoring; (6) Maintain BP <180/105 mmHg during and 24 hours after infusion; (7) Repeat CT head at 24 hours before resuming antithrombotics; (8) Report any sudden neurological deterioration — stop infusion immediately and order emergency CT for suspected symptomatic intracranial hemorrhage.

Evidence

NINDS rt-PA Stroke Study Group. Tissue plasminogen activator for acute ischemic stroke. N Engl J Med. 1995;333(24):1581-1587. PMID:7477192. ECASS-3: Hacke W et al. Thrombolysis with alteplase 3 to 4.5 hours after acute ischemic stroke. N Engl J Med. 2008;359(13):1317-1329. PMID:18815396. AHA/ASA Stroke Guidelines 2019: Powers WJ et al. Guidelines for the early management of patients with acute ischemic stroke. Stroke. 2019;50(12):e344-e418. PMID:31662037. Tenecteplase: Campbell BC et al. AcT trial. Lancet. 2022.

References

1. NINDS rt-PA Stroke Study Group. Tissue plasminogen activator for acute ischemic stroke. N Engl J Med. 1995;333(24):1581-1587. — link
2. Hacke W, Kaste M, Bluhmki E et al. (ECASS-3). Thrombolysis with alteplase 3 to 4.5 hours after acute ischemic stroke. N Engl J Med. 2008;359(13):1317-1329. — link
3. Powers WJ, Rabinstein AA, Ackerson T et al. Guidelines for the early management of patients with acute ischemic stroke: 2019 update. Stroke. 2019;50(12):e344-e418. — link
4. Campbell BCV, Mitchell PJ, Churilov L et al. (AcT Trial). Tenecteplase versus alteplase before thrombectomy for ischemic stroke. N Engl J Med. 2022;387(14):1265-1275. — link
5. Demaerschalk BM, Kleindorfer DO, Adeoye OM et al. Scientific rationale for the inclusion and exclusion criteria for intravenous alteplase in acute ischemic stroke. Stroke. 2016;47(2):581-641. — link