Pulmonary embolism (PE) is the third most common cause of cardiovascular death in the United States of America. It is one of the most common causes of death worldwide. Most patients die within the first few hours of presentation, making an early diagnosis and treatment paramount to survival. PEs are categorized into three main risk categories: low risk, intermediate (sub-massive) and high risk (massive). Submassive PEs are even further sub-divided into intermediate-high and intermediate-low risk PEs. Catheter-directed thrombolysis (CDT) is one of the newest treatment options for pulmonary embolism. CDT involves the use of infusing a thrombolytic agent intravascularly adjacent to the clot burden through a percutaneous transcatheter. This article will review the anatomy involved in the pathology of pulmonary embolisms, indications for CDT, contraindications for CDT, an overview of the CDT procedural technique, possible complications of CDT, and the clinical significance of CDT for PE.
Pulmonary embolisms usually arise from deep veins of the lower extremities and/or pelvis. Dislodgement of a DVT or parts of a DVT can result in the blood clot traveling up the venous system through the right heart and lodging in the pulmonary vasculature. The pulmonary trunk, main pulmonary artery, segmental or sub-segmental branches are all common locations for a pulmonary embolus to lodge. Once lodged in the pulmonary vasculature depending on the size and location of the PE, the blockage may result in hemodynamic heart strain along with a decrease in blood supply throughout the pulmonary vasculature. Some common hemodynamic changes include an increase in right heart pressures, increased pulmonary artery pressures, and a decreased diffusing capacity of the lungs for carbon monoxide (DLCO) resulting in cardiac compromise and hypoxemia. The most severe consequence of pulmonary embolus is sequential blockage the right and left pulmonary artery, which completely blocks the right heart outflow tract. This is known as a saddle embolus. Many times PEs resulting in hemodynamic instability involving the right heart system will lead to flattening of the intraventricular septum seen on echocardiography. This is an important diagnostic echocardiographic sign in determining the appropriate treatment pathway of PE.
Currently, CDT is a class 2C recommendation by the American College of Chest Physicians for the management of acute PE associated with hypotension and who have contraindications to thrombolysis, failed thrombolysis, or shock that is likely to cause death before systemic thrombolysis can take effect (eg, within hours), if appropriate expertise and resources are available.  This includes massive and intermediate-high submassive risk groups.
Several large studies have investigated the use of CDT for PE. For example, the 2014 PEITHO trial showed an increase in major bleeding including stroke during their investigation of tenecteplase versus UFH in the intermediate-risk population.  However, the 2015 PERFECT trial, CDT has a lower risk of bleeding compared to conventional systemic therapy. The 2014 ULTIMA trial was a randomized control trial which compared CDT to IV heparin in the intermediate-risk population which showed improvement in the RV: LV ratio with no difference in mortality at 90 days.  The 2015 SEATLE II study was a prospective multicenter study which revealed that ultrasound-guided catheter-directed, low-dose thrombolysis decreased right ventricular dilation, lessened pulmonary hypertension, reduced clot burden, and minimized intracranial bleeding in acute massive and submassive PE. Given this level of evidence, many centers base their decision to use CDT therapy off of the requirements for meeting massive and intermediate-high risk PE. Those patients determined to be in the intermediate low risk are not considered for thrombolytic therapy.
Though thrombolysis is administered locally during CDT, there is a risk of system effects of thrombolysis therapy. Systemic thrombolytic therapy is the cause for many of the severe complications of CDT (ie. severe bleeding). Therefore, the main contraindication to CDT is a high risk of bleeding. Any person with a prior ischemic stroke, cerebral bleed, cerebral mass, vascular deformation, recent ulcer in the gastrointestinal tract, recent brain/spine surgery, major abdominal or pelvic surgery, or any source of active hemorrhage are not considered candidates for CDT therapy. Dose adjustments are made for patients with moderate risk for bleeding to prevent these such complications. Those with contraindications to CDT therapy are usually contraindicated for systemic thrombolysis as well. These patient are treated with anticoagulant therapy, antiplatelet therapy, or supportive care only.
The equipment required for catheter-directed thrombolysis for pulmonary embolism includes an introducer needle or sheath, multiple-sized guide-wires, CDT catheter, ultrasonic core, thrombolysis therapy, a closure compression device, and an infusion system for the pharmacotherapies.
The new guidelines recommend a pulmonary embolism response team (PERT) approach. This is an interprofessional team that is alerted in the event of submassive or massive pulmonary embolism diagnosis. The team members job is to determine the best course of action to treat critically ill patients with massive PE. The PERF team usually consists of a pulmonologist and cardiologist. Other healthcare professionals who may be on the team include a cardiac nurse, pulmonary nurse, cardiac pharmacist, and pulmonary pharmacist. To perform CDT, a trained professional familiar with the chosen catheter system to perform the CDT procedure must be present (usually involves an interventional cardiologist or interventional radiologist).
Before the initiation of the procedure, the practitioner should inspect the thrombolysis catheter delivery system thoroughly to ensure all pieces are present. They may administer intravenous antibiotics before the procedure to prevent infection. This procedure requires a fully operating catheterization laboratory. Healthcare professionals should use proper sterile techniques including sterile drapes, gloves, and gowns.
First vascular access for placement of the CDT catheter is obtained. Typically a femoral approach is chosen, but occasionally jugular approach is pursued. Begin with the insertion of the introducer needle into the desired venous system followed by the threading of a guide-wire through the needle into the vasculature. The guide-wire is then guided up through the right heart into the pulmonary system adjacent to the thrombus. Using fluoroscopic guidance, the infusion catheter is passed over the guide-wire and across the treatment site. Note that radiopaque marker bands can be found at each end of the catheter to enhance catheter placement. Once positioned correctly, remove the guide-wire. Gently insert the ultrasonic core into the catheter until the fittings lock into place. Thrombolysis can now be administered. The thrombolysis exits the catheter through side holes while saline exits through the distal tip. Activating the ultrasonic waves enhances the dispersion of the thrombolysis medication. Typically, thrombolysis is administered for a standard 18 hours along with systemic heparin. The duration of thrombolysis may vary depending on the degree of hemodynamic instability and clot burden. After completion of thrombolytic therapy, a repeat CT angiography is performed to evaluate the improvement in clot burden. Depending on the results, the decision is made to pursue further thrombolytic therapy versus withdrawal of the CDT catheter. When the therapy is deemed complete, remove the ultrasonic core and replace the guide-wire inside the catheter. Next, remove the catheter leaving the guide-wire in place. Finally, remove the guide-wire and apply a compression device to the access site.
There are several possible complications from CDT for pulmonary embolus. Most complications are secondary to the increased risk of bleeding. One of the most common and most feared complications is hemorrhagic stroke which can be lead to a devastating outcome for the patient. Other common complications include vascular access related injury such as hematoma, pulmonary hemorrhage, retroperitoneal hemorrhage, cardiogenic shock, perforation or dissection of the pulmonary artery, arrhythmias, right-sided valvular regurgitation, pericardial tamponade, and contrast-induced nephropathy. 
Catheter-directed thrombolysis (CDT) is an alternative revascularization procedure to systemic thrombolysis, transcatheter embolectomy, or surgical embolectomy for PE. It is associated with some risks, but overall it reduces the systemic risk of thrombolytic therapy in patients with severe submassive or massive PE. The use of this therapy is on the rise in the United States as more healthcare professionals are becoming trained in the art of CDT. Overall, it saves lives and reduces the burden of pulmonary embolism (PE).
Catheter-directed thrombolysis is a minor procedure but just like all procedures it can have devastating complications if not done correctly. The current guidelines recommend all hospitals treating PEs to setup a pulmonary embolism response team (PERT). The PERT team is an interdisciplinary team made up of cardiologist, pulmonologist, and specialty-trained cardiac and intensive care nurses. They must work together to treat PE and to determine the best treatment plan and achieve the best outcomes. Once CDT is chosen as a management course, the team should counsel the patient and family regarding the risk and benefits of the procedure. A trained physician knowledgeable in the risk and benefits should have this discussion with the help of the nurses recording the discussion. The patient should give consent. An anesthesiologist or nurse anesthetist should evaluate the patient to determine the need, mode, and safety of anesthetic delivery. An imaging specialist or structuralist may consult for further recommendations on the size and burden of pulmonary embolism. The nurses must assist in monitoring the patient during the procedure and report any untoward affects. It is a level I recommendation to utilize this interdisciplinary approach. Studies have shown the PERF team can reduce adverse events. A swift and early diagnosis followed by early treatment is the key to successful thrombolysis of pulmonary embolism.
Due to the risk of complications during CDT, close monitoring during thrombolytic infusion is required. Most hospitals require ICU level monitoring during infusion. The patient should receive neuro checks every hour along with regular access site checks. Frequent blood draws are also required for thrombolytic infusion and anticoagulant monitoring. It is also recommended that the patient be monitored for 24-48 hours after infusion for possible complications. If any complications (ie signs of bleeding) are observed or abnormalities are seen in blood levels (PT, PTT, fibrinogen), a physician should be notified immediately.
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