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According to the Centers for Disease Control and Prevention, about 300,000 to 600,000 people are affected by thromboembolic events per year in the United States, ranging from deep venous thrombi affecting the extremities to pulmonary emboli. Pulmonary emboli (PE) can be divided into clinically asymptomatic PE that are often incidentally found, submassive, and massive PE. Submassive PE result in right ventricular (RV) dysfunction and evidence of myocardial necrosis such as elevated cardiac biomarkers, but occur without any hemodynamic instability, whereas massive PE are characterized by hypotension or cardiogenic shock. Saddle pulmonary emboli involve thromboemboli at the bifurcation of the pulmonary artery trunk and are one of the most severe types of PE. Patient outcomes in saddle emboli largely depend on early diagnosis and management. However, no ideal therapeutic model for management of patients with massive or saddle emboli currently exists, with therapy ranging from routine anticoagulation to thrombectomy. This case describes the use of ultrasound-assisted catheter-directed thrombolysis for treatment of a massive saddle embolus and a right atrial thrombus in a postoperative patient.
A 43-year-old male with a past medical history significant for hypertension, unprovoked lower extremity deep venous thrombus, and subsequent pulmonary embolus status post six months of anticoagulation in 2010, presented to the emergency department for evaluation of right lower quadrant pain that was made worse by ambulation and was associated with chills. Vital signs were within normal limits. Physical exam revealed right lower quadrant tenderness and voluntary guarding, but was otherwise unremarkable. Lab studies revealed a leukocytosis with a white blood cell count of 15,000. A contrast-enhanced computed tomography (CT) scan of the abdomen and pelvis showed perforated appendicitis with periappendiceal abscess. The patient was started on ciprofloxacin and metronidazole, and was taken to the operating room for an open appendectomy and abscess drainage.
On postoperative day 1, the patient became diaphoretic, hypoxic with an oxygen saturation of 80% on room air, tachycardic with heart rate around 120 beats per minute, and hypotensive with a systolic blood pressure of 70 mmHg. Electrocardiogram (ECG) revealed old right bundle branch block that was seen on previous ECGs, but no acute ST segment changes, and troponin level was elevated at 1.6. A bedside transthoracic echo (TTE) revealed an RV/left ventricular (LV) ratio >1.0, a large, mobile right atrial thrombus, severe right ventricular dilation and dysfunction, and was positive for McConnell’s sign (a pattern of right ventricular dysfunction with akinesia of the mid free wall of the right ventricle, but normal motion at the apex). A pulmonary angiogram and right heart catheterization confirmed the presence of a large saddle embolus obstructing the upper, middle and lower lobes, the right pulmonary artery, partially obstructing the left pulmonary artery, and a large, mobile, multilobular right atrial thrombus measuring 4x3cm.
Since the patient was in postoperative day 1 and was at high risk of bleeding, he was treated with tissue plasminogen activator (tPA) via an ultrasound-assisted catheter-directed infusion, specifically the EkoSonic Endovascular System (EKOS Corporation), placed in the right pulmonary artery.
A 7-French sheath was placed into the right femoral vein without incident, after which the inferior vena cava (IVC) angiogram was performed. A long J-wire was then advanced to the level of the right IVC. The 7-French APC catheter was advanced over the J-wire, right ventricular arterial pressures were measured, and a right ventricular angiogram was performed using the power injector. After reviewing the angiographic images and seeing the presence of a clot in the right atrium, 5mg of tPA was administered through the APC catheter. The APC catheter was advanced to the pulmonary trunk and using the power injector, a pulmonary angiogram was performed. After reviewing the pulmonary angiogram, the APC catheter was advanced to the right pulmonary artery and another angiographic image in digital subtraction mode using the power injectors was obtained. Another 5mg of tPA was administered through the APC catheter and a Wholey wire was advanced through the APC catheter. The APC catheter was removed, leaving the Wholey wire in place in the right pulmonary artery. The 40-cm EkoSonic catheter was advanced over the Wholey wire, leaving it in the right pulmonary artery. Heparin and tPA infusions continued to be administered during the case through the APC catheter and the venous sheath, respectively. The EkosSonic catheter was sutured in place.
The initial dose of 5mg of tPA given via an APC catheter in the right pulmonary artery was followed by 2mg of tPA for four hours, and then 1mg of tPA for twelve hours, for a total dose of 25mg of tPA. The patient was transferred to the intensive care unit for hourly vital signs and groin site checks (to monitor for bleeding). Head of bed was maintained at less than 30 degrees with patient lying supine, and periodic checks were performed to make sure the EkoSonic machine was running. The system runs for 12 hours at a minimum.
A repeat pulmonary angiogram twenty-four hours after placement of the EkoSonic system showed resolution of the right atrial thrombus, resolution of the right saddle embolus with a small non-obstructing thrombus still visible in the right upper pulmonary artery, and complete resolution of the left pulmonary artery thrombus. Repeat TTE showed normal RV size and systolic function.
Pulmonary emboli (PE) are a well-known complication that may occur in post surgical patients, as well as other patient populations. PE has high mortality rates, causing an estimated 200,000 deaths per year in the U.S, and it is the third most common cause of death in hospitalized patients.1 Early mortality in patients with massive PE is at least 15%, and the degree of hemodynamic compromise is the most powerful predictor of in-hospital death.2 As a result, aggressive thrombolytic therapy is warranted for management of massive PE.
Since there is no therapeutic algorithm for managing patients with different types of PE, submassive and massive PE may be treated with oral anticoagulants, systemic thrombolysis, thrombectomy, or catheter-directed thrombolysis.3 When comparing the above options, one can make a case for the use of catheter-directed thrombolysis in submassive and massive PE, supported by the ULTIMA and SEATTLE II trials. The ULTIMA study4,5 was a randomized, controlled trial that compared management of patients with submassive PE resulting in RV dilation (as evidenced by RV/LV ratio ≥1.0 on echocardiogram) with unfractionated heparin (UFH) alone, the current standard of care, versus ultrasound-assisted catheter-directed thrombolysis. Patients were randomized to treatment with either UFH alone or an ultrasound-assisted catheter-directed thromobolysis approach using an EKOS EkoSonic device. Participants in the intervention arm received 10mg of catheter-directed tenecteplase over 15 hours in either one or both affected lungs. The primary endpoint was the change in RV/LV ratio from baseline to 24 hours. The trial concluded that an ultrasound-assisted catheter-directed thromobolysis approach is associated with accelerated improvement in hemodynamic and echcardiographic risk indices in patients with submassive PE with reasonable safety profile.
The SEATTLE II study6,7 was a prospective, single-arm, multi-center trial that evaluated the safety and efficacy of ultrasound-assisted catheter-directed low-dose thrombolysis, using the Ekos EkoSonic Endovascular System. The study included 150 patients with acute massive (n=31) or submassive (n=119) PE, with evidence of dilated right ventricle (RV/LV ratio ≥0.9) on chest computed tomography. A dose of 24mg tPA was used in the trial, administered either as 1 mg/hour for 24 hours with a unilateral catheter or 1 mg/hour/catheter for 12 hours with bilateral catheters. The mean RV/LV ratio in the study decreased from 1.55 pre-procedure to 1.13 at 48 hours post-procedure, a difference of 0.42 (P<0.0001).
Massive PE has a mortality rate of about 52% at 90 days.8 In the SEATTLE II study, there were 31 patients presenting with massive PE, manifested by syncope and hypotension. However, no patients with massive PE died within the 30-day follow-up period. Of 150 patients in the overall study, only one death was directly attributed to PE.
There were no intracranial hemorrhages and no fatal bleeding events. The abstract concluded that ultrasound-facilitated catheter-directed low-dose fibrinolysis for acute PE minimizes the risk of intracranial hemorrhage, improves RV function, and decreases pulmonary hypertension.
In our post-surgical, hemodynamically unstable patient with a massive saddle PE, emergent therapy was needed. Ultrasound-assisted catheter-directed thromobolysis was seen as the safest therapeutic modality given patient’s increased morbidity and mortality in the event of bleeding. The above trials support the use of catheter-based thrombolysis and demonstrated superiority in management of massive and submassive PE as compared to conventional therapy in rapidly unloading the right heart, and prevented further deterioration and complications associated with right heart failure, with the added benefit of no increased risk of bleeding.
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- Kucher N, Boekstegers P, Müller OJ, et al. Randomized, controlled trial of ultrasound-assisted catheter-directed thrombolysis for acute intermediate-risk pulmonary embolism. Circulation. 2014; 129: 479-486.
- Safadi A. Ultrasound-assisted, catheter-directed, low-dose thrombolysis: a safer alternative to systemic thrombolytics for pulmonary embolism. Cath Lab Digest. Sept 2014; 22(9). Available online at http://www.cathlabdigest.com/articles/Ultrasound-Assisted-Catheter-Directed-Low-Dose-Thrombolysis-Safer-Alternative-Systemic-Thro. Accessed August 24, 2015.
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