In this episode, I’ll cover when, why, and how to give alteplase for massive pulmonary embolism (PE). I’ll also touch on bleeding risk and whether to stop or continue the heparin infusion while you give the alteplase.
First, let’s define massive PE. Massive pulmonary embolism is present when a patient has an acute PE and hypotension, profound bradycardia, or cardiac arrest.
When to give alteplase
There is broad agreement among experts to administer alteplase in the setting of massive PE. It makes good sense considering the pathophysiology – the clot has to go for oxygenation to return. Anti-thrombotics like heparin and enoxaparin aren’t going to do a thing to the existing clot – they will just prevent the clot from getting bigger.
The specific CHEST Guideline statement is: In patients with acute PE associated with hypotension (systolic BP , 90 mm Hg) who do not have a high bleeding risk, we suggest systemically administered thrombolytic therapy over no such therapy (Grade 2C) .
Why is alteplase given in massive PE
The hope is that mortality will be decreased by lysing the clot. In the 2012 CHEST guidelines, the authors note that there is only a trend pointing towards a mortality benefit with lytic therapy. Since the publication of those guidelines there has been a meta-analysis which does point to an association with lower all-cause mortality with lytic therapy. However the wide range of patient groups and treatments in this meta-analysis leaves many unanswered questions. Even though the available evidence is less than ideal, I doubt further trials will compare lytic therapy to placebo in massive PE given the clear pathophysiology and rationale for lytics. As the CHEST guidelines state: Patients with the most severe presentations who have the highest risk of dying from an acute PE have the most to gain from thrombolysis.
Plenty of “soft endpoints” are improved after alteplase is given for massive PE. Clot lysis is accelerated and there is early hemodynamic improvement (eg, improved pulmonary arterial blood pressure, right ventricular function, and pulmonary perfusion). There is, as you would expect, an increased risk of major bleeding.
In most cases, thrombolytic therapy should be considered only after acute PE has been confirmed because the bleeding events after thrombolytic therapy can be severe.
How to give alteplase for massive PE
There are three options for alteplase administration in massive PE. They are catheter directed therapy, IV push, or IV infusion.
Catheter directed therapy
For massive PE, this is a fringe option and would only be used for patients who do not have a low bleeding risk but still appear to need lytic therapy. Catheter directed therapy involves infusing alteplase into the pulmonary artery at a rate of 0.5 to 2 mg/hr. An ultrasound device may be used to assist in the delivery of alteplase, with the ultrasound creating additional surface area on the clot for the alteplase to lyse.
Another role for catheter directed lytic therapy in massive PE is as a “rescue” therapy if systemic thromblysis has failed.
IV push
If a patient with an acute PE appears to have an imminent cardiac arrest, or has already arrested, alteplase should be given IV push. CHEST guidelines specifically state this so you can be confident you are not out on a limb if this is being ordered. IV push alteplease is always a disturbing thought for pharmacists but remember the pathophysiology – if the clot doesn’t go away, the patient will not get any oxygen. Another comforting thought is that longer infusion times are associated with higher bleeding risk compared to shorter infusion times.
Case reports and series have reported some success from systemic thrombolytic therapy during cardiopulmonary resuscitation when the cardiac arrest is due to suspected or confirmed acute PE.
IV infusion
If the patient has a pulse and is of low bleeding risk, IV infusion is the way alteplase should be given. I typically use 100 mg IV over 2 hours but there have been additional studies suggesting that 50 mg IV over 15 minutes is just as safe and effective. The CHEST guidelines note that the 100 mg over 2 hours regimen has been studied more extensively.
Bleeding risk
Robust data on bleeding risk is lacking. The CHEST authors assume that the bleeding risk with thrombolytic therapy is similar in patients with PE as with acute ST-segment elevation myocardial infarction. This puts the risk of intracranial hemorrhage (ICH) at about 1% or less. Other serious types of bleeds are more common, but because the risk of ICH is so much lower than when alteplase is given for stroke, most clinicians I’ve talked to agree that patients who received alteplase for PE do not need the same type of neurologic monitoring as those who received it for stroke.
What to do with the heparin infusion
CHEST guidelines cover this very well. They say it is acceptable to either continue or suspend the UFH infusion during administration of thrombolytic therapy (these two practices have never been compared). During a 2-h infusion of 100 mg of alteplase, US regulatory bodies recommend suspension of IV UFH, whereas IV UFH is continued during the alteplase infusion in many other countries. US authorities recommend checking the activated partial thromboplastin time immediately after completion of the alteplase infusion and, provided that the activated antithrombin time is not > 80 s, restarting IV UFH without a bolus at the same infusion rate as before alteplase was started.
Usually, after I inform the physician of the statement in the CHEST guidelines they make the decision to hold the heparin infusion while the alteplase is running.
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What dose and how fast would you push?
I would give the same dose that you would for unstable PE – usually this is 100 mg. I would push it over a few minutes (it would be hard to do it any faster since the volume is 100 mL) as this is what I believe the CHEST guidelines mention.
Uptodate recommends 50 mg iv push over 2 minutes, if not resolved after 15 minutes give another 50 mg iv push over 2 minutes.