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. Many patients die within the first few hours of presentation, making an early diagnosis and treatment paramount to survival. Pulmonary embolisms are categorized into three main risk categories: low risk, intermediate (sub-massive), and high risk (massive). Submassive PEs are further sub-divided into intermediate-high and intermediate-low risk PEs. Catheter-directed thrombolysis (CDT) is one of the newest treatment options for massive and submassive pulmonary embolisms with hemodynamic instability. CDT involves the infusion of 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 originate from the deep veins of the lower extremities and/or pelvis. Dislodgement of a deep vein thrombus (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 to the downstream pulmonary parenchyma. 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 the sequential blockade of the right and left pulmonary artery, which completely blocks the right heart outflow tract. This is referred to as a saddle embolus due to the radiographic/anatomic shape of the embolus. PEs resulting in hemodynamic instability involving the right heart system will often lead to flattening of the intraventricular septum on echocardiography. This is an important diagnostic echocardiographic sign in determining the appropriate treatment pathway for a 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), and 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 unfractionated heparin (UFH) in the intermediate-risk population. However, the 2015 PERFECT trial, reported that CDT has a lower risk of bleeding as compared to conventional systemic therapy. The 2014 ULTIMA trial was a randomized control trial that compared ultrasound-assisted CDT to intravenous (IV) heparin in the intermediate-risk population. They concluded that in this population CDT was superior to anticoagulation in reversing right ventricular (RV) dilatation. They also reported no increased bleeding risk or 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 pursue CDT therapy for patients with massive and intermediate-high risk submassive 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 systemic effects of thrombolysis therapy. Systemic thrombolytic therapy is the cause of many of the severe complications of CDT (i.e., 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 bleeding 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 patients are treated with anticoagulant therapy, antiplatelet therapy, or supportive care only.
The equipment required for catheter-directed thrombolysis for pulmonary embolism includes:
The new guidelines recommend a pulmonary embolism response team (PERT) approach at healthcare facilities. This is an interprofessional team that is alerted in the event of submassive or massive pulmonary embolism diagnosis. The team members include multiple clinical providers from emergency medicine, internal medicine, critical care, cardiovascular, vascular surgery and interventional radiology specialties. The team also consists of specialized nurses and pharmacists to assist in the delivery of CDT once the decision is made to pursue that course. On initial referral to the PERT team, the clinicians determine the best course of action to treat critically ill patients with massive and submassive PE. 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, the guide-wire is removed. The proceduralist then gently inserts 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 computed tomography (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 the withdrawal of the CDT catheter. When the therapy is deemed complete, the ultrasonic core is removed, and the guide-wire is replaced inside the catheter. The proceduralist then removes the catheter leaving the guide-wire in place. Finally, the guide-wire is also replaced, and a compression device to the access site is applied.
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 a hemorrhagic stroke, which can 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 massive and submassive PE with hemodynamic instability and a high risk of morbidity and mortality with the standard care. It is associated with some risks, but overall it reduces the systemic risk of thrombolytic therapy in patients with severe submassive or massive PE and a high risk of bleeding. 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 (CDT) offers improved clinical outcomes in patients with severe, hemodynamically unstable, massive or submassive PEs. Without CDT, these patients are at a higher risk of morbidity and mortality. The current guidelines recommend all healthcare facilities treating PEs to set up a pulmonary embolism response team (PERT).
The PERT team is an interprofessional team that consists of specialists from various clinical fields including emergency medicine, critical care, cardiology, internal medicine, and radiology, as well as specialty-trained nurses from critical care, radiology, and emergency care. Clinical pharmacists especially those trained in critical care, cardiac care, and anticoagulation are an essential part of this team as well. Working as a collaborative team, they can help deliver CDT efficiently and effectively to improve patient care.
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 clinical provider knowledgeable in the risk and benefits should have this discussion with the help of the nurses to ensure informed consent has been obtained. An anesthesiologist or nurse anesthetist should then 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 the pulmonary embolism. The emergency care and critical care nurses must assist in monitoring the patient during the procedure as well as during subsequent infusion therapy to monitor for hemodynamic or neurologic complications. The clinical pharmacists assist the interventional team by providing appropriate medication and dosing for the procedure. The critical care pharmacist must assist the team in adjusting other concurrent medications to minimize adverse side-effects.
Multiple studies have shown that institution of a PERT team can reduce adverse events in regards to PE care. A swift and early diagnosis followed by early treatment is the key to the successful thrombolysis of pulmonary embolism.
Due to the risk of complications during CDT, close monitoring during thrombolytic infusion is required. Most hospitals require intensive care unit level monitoring during infusion. The patient should receive neurologic checks every hour along with regular vascular access site checks to monitor for early signs of possible complications. It is also recommended that the patient be monitored for 24-48 hours after infusion for possible complications in the same manner. If any complications (ie signs of bleeding or an acute neurologic event) are observed or abnormalities are seen laboratory data a clinician should be notified immediately.
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