In this episode, I’ll discuss catheter-directed alteplase for pulmonary embolism.
Catheter-directed alteplase for pulmonary embolism involves the placement of a central venous catheter in the pulmonary arteries via the common femoral or internal jugular vein.
The catheter is placed adjacent to the PE, and the alteplase is infused directly into the thrombus. In some cases, ultrasound assisted catheters are used. The addition of ultrasound waves serves to disrupt the thrombus and increase the surface area exposed to alteplase in the hope of faster and more complete dissolution of the clot.
Ongoing research continues to shed light on what types of patients with pulmonary embolism may be ideal candidates for catheter-directed alteplase.
High-risk patients with a PE and hypotension or who are hemodynamically unstable should receive prompt systemic alteplase infusions. The 2016 CHEST guidelines give a 2C recommendation when using alteplase to use systemic over catheter-directed therapy.
Low-risk patients with a PE are given anticoagulation and if possible home treatment or an early discharge.
But there is a significant subset of patients with PE that are considered intermediate risk. Such patients are hemodynamically stable but have acute right ventricular dysfunction and myocardial injury. Up to 5% of these patients go on to experience hemodynamic compromise or death.
The ideal management strategy for intermediate risk patients with PE is the subject of ongoing research and debate. A 2014 trial gave placebo or systemic thrombolytic therapy to intermediate risk PE patients. Although hemodynamic compromise was lower in the treatment group, mortality was unchanged and the risk of hemorrhage and stroke was increased with thrombolytic therapy.
It is precisely these intermediate-risk patients with PE that catheter-directed alteplase is aimed at helping. Instead of giving the full 100 mg systemic dose of alteplase over 2 hours, catheter-directed regimens infuse as little as 8 mg or as much as 25 mg over a 2 to 24 hour period. The hope is such regimens will offer a reduced risk of major bleeding or hemorrhagic stroke.
The trials of catheter-directed alteplase have generally been very small in terms of enrollment numbers.
The first RCT of ultrasound-assisted catheter-directed thrombolysis for acute intermediate-risk pulmonary embolism was the ULTIMA trial. Only 30 patients were in the treatment group. An improvement was found in the surrogate measure of decreased mean RV/LV ratio.
A more recent study of 77 patients attempted to find the optimal dose and duration of ultrasound-assisted alteplase by comparing 8 mg over 2 or 4 hours with 12 mg over 6 hours and 24 mg over 6 hours. No major bleeding occurred in the 8 or 12 mg groups in this study while still improving echocardiographic measures of RV function.
One method that is growing in popularity to identify the best patients for catheter-directed therapies is a PE response team, or PERT, which I discussed in episode 146.
The most important thing for a pharmacist to be aware of with the use of catheter-directed therapies is the use of concurrent heparin for anticoagulation. Heparin infusions are generally held temporarily when systemic alteplase is being infused but are continued concurrently when catheter directed alteplase is being infused. All study protocols that I was able to review involve the provision of full-dose heparin therapy for anticoagulation concurrent with catheter-directed alteplase.
Patients with catheter-directed alteplase will usually need two infusions of heparin. This is because most protocols involve 250 to 500 units/hr of heparin being infused into the sheath in the vein that contains the catheter to prevent clotting. The balance of the heparin needed to provide full-dose anticoagulation is then administered in a separate vein. Nurse flowsheets should be designed to accommodate calculating the heparin infusion rates taking into account the use of 2 infusion bags.
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Joe it has been my experience that aPTTs are not accurate to measure systemic heparin during tPA infusions, we use sheath heparin only doing catheter directed lysis and start a DOAC immediately upon discontinuing tPA