What is the recommended dose of alteplase (tissue plasminogen activator) for massive pulmonary embolism (PE)?

Recommended Dose of Alteplase for Massive Pulmonary Embolism

For massive pulmonary embolism, the FDA-recommended dose of alteplase is 100 mg administered as a continuous intravenous infusion over 2 hours. 1

Dosing Protocol

• Administer alteplase via a peripheral intravenous catheter 1
• The full dose should be 100 mg given as a continuous infusion over 2 hours 1
• Anticoagulation with heparin should be withheld during the 2-hour infusion period, as recommended by the FDA 1
• Resume anticoagulation after the completion of the alteplase infusion 1

Alternative Dosing Regimens

• For patients in cardiac arrest due to suspected massive PE, a more rapid administration may be considered:

  • 50 mg alteplase IV bolus immediately for patients in cardiac arrest or with deteriorating condition 2
  • In life-threatening situations, a second 50 mg bolus may be considered if there is persistent hemodynamic compromise after the initial bolus 3

• Some studies have investigated alternative dosing regimens:

  • A bolus dose of 0.6 mg/kg over 15 minutes has been studied with favorable outcomes in patients with massive PE and shock 4
  • Double bolus regimens (two 10-unit boluses of reteplase 30 minutes apart) have shown comparable efficacy to the standard 100 mg/2-hour alteplase infusion 5

Clinical Decision Making

• Massive PE is defined as obstruction of blood flow to a lobe or multiple segments of the lung with unstable hemodynamics (failure to maintain blood pressure without supportive measures) 1
• Indications for thrombolytic therapy in massive PE include:
  • Sustained hypotension (systolic blood pressure <90 mmHg for at least 15 minutes) 1
  • Shock index >1.0 (heart rate divided by systolic blood pressure) 1
  • Evidence of respiratory failure 1

Risk Assessment and Contraindications

• Before administering alteplase, assess for bleeding risk factors which significantly increase the odds of major bleeding:

  • Recent major surgery (increased odds by 9-fold) 6
  • INR above 1.7 (increased odds by 13-fold) 6
  • Lower body weight (each 10 kg below 100 kg increases bleeding risk by 18%) 6

• Patients with one or more risk factors for bleeding have approximately 5 times higher odds of major bleeding 6

Monitoring and Follow-up

• Monitor hemodynamic parameters during and after thrombolysis 5
• Expect improvement in pulmonary vascular resistance and mean pulmonary artery pressure within the first 2 hours 5
• Be prepared to manage potential bleeding complications, which occur in 10-40% of patients 1

Special Considerations

• In life-threatening PE, contraindications to thrombolysis may need to be reconsidered given the high mortality rate without treatment 2
• It is preferable to confirm the diagnosis of PE with imaging before fibrinolysis is initiated, but when direct imaging is unavailable or unsafe due to the patient's unstable condition, fibrinolysis may be considered based on high clinical suspicion and evidence of RV dysfunction on bedside echocardiography 1
• Bedside echocardiography can be valuable in guiding treatment decisions, particularly when considering additional doses of thrombolytics 3