Thrombolytics for Acute Pulmonary Embolism
from the ACCP Guidelines, 9th Ed.
The ACCP’s recommendation classification system:
- 1 = “recommendation”
- 2 = “suggestion”
- A = based on strong evidence from randomized trials
- B = moderate evidence that may include randomized trials or observational studies
- C = weak evidence, mostly consensus opinion
Which patients with acute pulmonary embolism should I treat with systemic thrombolytics?
- The ACCP suggests using systemic thrombolytics to treat patients with acute PE who are hypotensive (they propose a cutoff of systolic blood pressure less than 90 mm Hg). (Grade 2C).
- ACCP recommends against treating most patients with acute PE without hypotension with systemic thrombolytics (Grade 1C).
- However, patients deemed to be at high risk for becoming hypotensive according to clinical course are suggested to receive systemic thrombolytics, if they have a low bleeding risk (Grade 2C). “Looking sick,” dyspneic and hypoxic, right ventricular dysfunction on echocardiogram, elevated troponins, elevated neck veins, severe tachycardia have all been proposed as risk factors.
How should I treat acute pulmonary embolism with systemic thrombolytics?
- A short infusion time of 2 hours for systemic thrombolytics is suggested, rather than a longer infusion (Grade 2C). Tissue plasminogen activator (tPA) has a short infusion time and has been recommended as the best agent for this reason.
- Infuse systemic thrombolytics through a peripheral vein, rather than a pulmonary artery catheter (Grade 2C).
Randomized trials show that thrombolytics improve pulmonary artery pressures, oxygenation, and cardiac performance on echocardiography within 24 hours in people with acute pulmomary embolism. However, this comes at a significantly higher risk of bleeding compared to other therapies.
13 randomized trials and their meta-analyses suggest that thrombolytic therapy may reduce mortality and recurrent pulmonary embolus, but reviewers share a high suspicion for publication bias and uneven quality between studies. In other words, thrombolytics’ benefits in reducing mortality from acute PE remain unknown. Further, risk stratification models have not been validated prospectively (neither those predicting death from PE nor those predicting bleeding from thrombolytic therapy), so risk / benefit calculations in determining the ideal candidate for thrombolytic therapy are more art than science.
Trying to reconcile the uncertainty in the existing data, ACCP’s recommendations to provide thrombolytics to people with massive PE (with hypotension) or who are high risk for soon becoming that way. In large part, this is based on the observed mortality seen in series of patients with acute pulmonary embolism:
- ~5% of people with pulmonary embolus who receive treatment die (from that or another PE) within 7 days.
- ~2% mortality in patients without hypotension;
- ~30% mortality when there is shock necessitating inotropes;
- ~70% mortality if cardiopulmonary arrest occurs.
What shall I do with the heparin infusion during administration of thrombolytic therapy for acute PE?
There is no ACCP recommendation for this question, stating it is “acceptable … to continue or suspend the unfractionated heparin infusion during administration of thrombolytics.” In the U.S., regulatory bodies advise stopping unfractionated heparin during t-PA infusion and restarting it when aPTT is <= 80 sec after t-PA is complete. In many other countries, heparin infusion is continued during t-PA.
Kearon C et al. Antithrombotic Therapy for VTE Disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. CHEST 2012;141 (suppl 2): e419-e494S