Alteplase Dosing for Massive Pulmonary Embolism
For massive PE (defined as PE with sustained hypotension <90 mmHg or shock), administer alteplase 100 mg as a continuous intravenous infusion over 2 hours via peripheral IV catheter. 1, 2, 3
Standard Dosing Protocol
The FDA-approved dose is 100 mg administered as a continuous IV infusion over 2 hours, which is the first-line therapy recommended by the American Heart Association and American College of Cardiology 1, 2, 3
Administer through a peripheral intravenous catheter rather than a central line or pulmonary artery catheter 1, 3
Withhold all heparin anticoagulation during the entire 2-hour alteplase infusion period 1, 2
Resume unfractionated heparin 3 hours after completion of the alteplase infusion, or when APTT is less than twice the upper limit of normal, using weight-adjusted dosing (typically 1280 IU/hour continuous infusion) 2, 3
Modified Dosing for Critical Situations
For patients in cardiac arrest or with rapidly deteriorating hemodynamics, give 50 mg alteplase as an immediate IV bolus 1, 2, 3
This bolus regimen is specifically for life-threatening situations where the patient cannot wait for the 2-hour infusion 2, 3
Diagnostic Confirmation Requirements
Preferably confirm PE diagnosis with CT pulmonary angiography or V/Q scan before initiating thrombolysis 2, 3
However, when the patient is too unstable to safely transport for imaging, thrombolysis may be initiated based on high clinical suspicion combined with bedside echocardiography showing right ventricular dysfunction 1, 2
Contraindications Assessment
In life-threatening massive PE, most relative contraindications should be reconsidered given the high mortality without treatment 1, 3
Absolute contraindications that should still be respected include prior intracranial hemorrhage, known structural intracranial vascular disease, and known malignant intracranial neoplasm 3
Relative contraindications include recent surgery (within 7 days), peptic ulcer disease, prolonged cardiopulmonary resuscitation, and current gastrointestinal hemorrhage 2
Monitoring and Bleeding Risk
Major bleeding occurs in approximately 8-9% of patients, with intracranial hemorrhage in approximately 1% 3
Continuous cardiac monitoring, serial blood pressure measurements, and oxygen saturation monitoring are essential during and after treatment 3
Be prepared to manage bleeding complications, which can occur in 10-40% of patients overall 1
Evidence Nuances
The 100 mg over 2 hours regimen is superior to prolonged 24-hour infusions and has been validated in multiple trials 3. While some studies have explored reduced-dose regimens (50 mg total dose or 0.6 mg/kg), these have not shown clear advantages and may be associated with higher mortality rates in certain populations 4, 5, 6. The standard 100 mg over 2 hours remains the evidence-based recommendation from all major guideline societies 1, 2, 3.
Alternative Thrombolytics
Reteplase (10 U + 10 U as double bolus 30 minutes apart) has shown equivalent efficacy to alteplase in research studies, though alteplase remains the FDA-approved and guideline-recommended agent 7
Streptokinase (1.5 million IU over 2 hours) has similar efficacy but is less commonly used in current practice 8