Gardner L. Yost and Jonathan W. Haft
This chapter is a revision and update of that included in the previous editions of the TSRA Review written by Patrick Rudersdorf (2nd edition) and Serguei I. Melnitchouk (1st edition).
Introduction
Acute pulmonary embolism (PE) is the third most common cause of death in the United States, after heart disease and cancer, and results in more than 630,000 symptomatic episodes yearly. 2.5 million Americans are diagnosed with deep vein thrombosis (DVT), and more than 90% of known PE are associated with lower extremity DVT. Acute PE rarely necessitates surgical intervention, except for cases in which significant clot burden results in life-threatening cor pulmonale, large mobile thrombi within the right atrium or ventricle, or a paradoxical embolus in transit. However, surgical intervention is the treatment of choice for chronic pulmonary thromboembolism.
Pathophysiology and Natural History of DVT and Acute PE
The vast majority of PE are associated with lower extremity and pelvic DVT. These blood clots break off the wall of the vessel and travel through the right side of the heart into the pulmonary circulation. This process, referred to venous thromboembolism (VTE), produces a constellation of symptoms resulting from RV pressure overload and V:Q mismatch. The causes of DVT include venous stasis, vein wall injury, and hypercoagulopathy, which together comprise Virchow’s Triad. In hospitalized patients, immobilization is the most important cause of venous stasis, coupled with relative hypercoagulability associated with a postoperative state, infection, or malignancy. Genetic causes of hypercoagulopathy include deficiencies in antithrombin, Protein C, Protein S, and the Factor V Leiden mutation.
Embolic thrombi enter the pulmonary arteries via the right heart before lodging in the branch vessels, affecting the lower lobes more frequently because they receive a larger fraction of the cardiac output. Once immobilized within pulmonary arteries, the clot propagates as a result of stasis and activation of platelets and local endothelial cells. Activated platelets then release vasoconstrictors including serotonin, thromboxane, and adenosine diphosphate, further increasing pulmonary vascular resistance (PVR). The resulting re-distribution of blood flow causes V:Q mismatch and hypoxemia and the elevated PVR drives increased RV afterload that may lead to RV dilation, ischemia, and dysfunction. RV failure may result in tricuspid regurgitation, elevated CVP, and decreased LV preload leading to decreased cardiac output, systemic hypotension, and organ congestion.
Untreated, the mortality of acute PE is 18-33%, but is reduced to 8% if treated. Lysis of the emboli occurs over days to weeks in patients whose cardiopulmonary reserve is sufficient to survive the initial insult.
Presentation and Diagnosis
- Symptoms
- Minor emboli present as sudden anxiety, tachypnea, tachycardia, pleuritic chest pain, cough
- Sub-massive emboli present as the above symptoms with mild hemodynamic instability including relative hypotension, and elevated CVP.
- Massive emboli present as the above with life threatening hemodynamic instability. This is usually a result of occlusion of more than 50% of the pulmonary vasculature. Blood gases will reveal hypoxia and hypocarbia.
- EKG: Non-specific T-wave and ST-segment changes. T-wave inversion in the anterior leads indicate ischemia inferiorly from pressure overload. The classic pattern is S1Q3T3 (S wave on lead I, and Q and T waves in lead III).
- CXR: Non-specific findings; pleural effusion may be present. Notable is the absence of other causes of hypoxia (infiltrates, edema, or effusions).
- D–dimer: A fibrin degradation product, indicating fibrinolyisis; D-Dimer is elevated in acute PE or DVT.
- CT pulmonary angiogram: Considered the gold standard in the diagnosis of acute PE. Will show size and location of clot(s).
- Echocardiography: Demonstrates RV pressure overload, dysfunction, or distention. May show tricuspid regurgitation, paradoxical septal motion, or congestion of the IVC. TEE may identify thrombus in the main PA or central branches.
Treatment of Acute Pulmonary Embolism
Management begins with cardiorespiratory stabilization followed by aggressive anticoagulation. Heparin prevents propagation of existing thrombi but does not cause clot lysis. Therapeutic anticoagulation permits fibrinolysis of the clot by endogenous factors over the period of days to weeks. ECMO may be used for cardiorespiratory support in the patient with profound hemodynamic compromise and may be continued until clot lysis results in reduced pulmonary vascular resistance. Systemic thrombolysis with 100 mg of tPA (alteplase) may be used to accelerate the lysis of thromboemboli when the diagnosis of PE has been confirmed and when the risk to benefit ratio is favorable. Thrombolytic therapy is associated with reduced all-cause mortality, reduced recurrent PE, and with improvement in RV function in hemodynamically unstable patients. Thrombolytic therapy increases the risk of bleeding, most importantly, of intracranial hemorrhage, which occurs in up to 5 percent of patients.
Transcatheter thrombolysis
Transcatheter thrombolysis (flow-directed PA catheter thrombolysis) is not currently the gold standard but is an emerging procedure for treating massive and submassive PE.
Acute pulmonary embolectomy
Indications
Primary indications for acute pulmonary embolectomy are uncertain. There may be an indication for massive PE with cardiovascular collapse and submassive PE with RV dysfunction and troponin leak in the absence of shock, when catheter-based treatments are unavailable and systemic lytic therapy is contraindicated. Large highly mobile thrombi in transit within the right atrium or ventricle require urgent surgical treatment, along with trapped thrombi within a patent foramen ovale (paradoxical embolus in transit).
Surgical technique
A midline sternotomy is performed followed by central cannulation. Many of these patients are profoundly hemodynamically unstable which can be exacerbated by induction of general anesthesia. The surgical team must be prepared to proceed at a rapid pace if necessary. Peripheral cannulation may be an acceptable alternative if it is believed to afford more expedient initiation of bypass. Cardioplegia and cross-clamping are required if a PFO is noted to avoid air embolization.
The main PA is incised longitudinally 1-2 cm distal to the pulmonic valve; the conal branches of the RCA may be used as landmarks for this arteriotomy. Suction and forceps are used to remove emboli. If thrombus is located in the left PA, this incision may be extended towards the pericardial reflection on the left pulmonary artery. If thrombus is located in the right PA beyond the bifurcation, a separate incision in the right PA can be made longitudinally between the SVC and aorta.
If necessary, additional maneuvers may be performed to further remove clot. The pleural spaces may be opened and the lungs compressed to expel distal clot. Retrograde perfusion may be used through the pulmonary veins to flush clot in a retrograde direction; this requires aortic cross clamping and cardioplegia. Once complete, the pulmonary arteriotomies are then closed. Patching is rarely necessary.
Anticoagulation should be initiated in the post-operative period once chest tube output is acceptable. The patient should be remain on oral anticoagulation for at least 6 months, or longer if this represented a recurrent PE or was felt to be unprovoked. In that setting, referral to a hematologist should be obtained to assess for hypercoagulable disorder.
Chronic Thromboembolic Disease
Incidence
Chronic thromboembolic pulmonary hypertension (CTEPH) is thought to develop in 0.5–5% of patients with acute PE as a result of incomplete thrombolysis.
Pathogenesis
Inadequate thrombolysis may occur from lack of anticoagulant treatment or an associated hypercoagulable disorder. Fibrin within the clot progressively becomes cross linked and organized leading to incorporation and endothelialization. In some cases, partial lysis results in recanalization leaving webs or stenoses.
The phenomenon of CTEPH results only partially from the mechanical obstruction to the segmental branches of the pulmonary vasculature. Blood flow is redirected into the relatively unobstructed segments. These hyperperfused segments undergo pulmonary vascular changes, similar to Eisenmenger’s syndrome from excessive pulmonary blood flow associated with untreated congenital heart disease. These pulmonary vascular changes include medial hypertrophy, vasoconstriction, and the formation of plexiform lesions and thrombosis. This constellation of findings results in progressive pulmonary hypertension and right ventricular failure in the absence of recurrent pulmonary emboli.
Presentation and Diagnosis
The most common presenting symptom is dyspnea, often out of proportion to clinical exam. Patients may also complain of chest pain, hemoptysis, and peripheral edema.
CTEPH should be suspected in patient with mean PA pressures greateter than 35 mmHg more than 6 months after PE. Confirmatory testing, including invasive cardiopulmonary exercise testing, is required. Further, chest X-ray may demonstrate right heart enlargement and a dilated pulmonary artery. Echocardiogram will identify pulmonary hypertension using the tricuspid regurgitation jet velocity. In the absence of other causes of pulmonary hypertension (left heart disease, advanced pulmonary parenchymal pathology), a VQ scan is indicated. A normal result excludes the diagnosis of CTEPH, but the presence of any mismatched ventilation:perfusion defects warrants further testing. Pulmonary angiography remains the gold standard for the diagnosis of CTEPH and will clarify the burden of disease and surgical accessibility.
Pulmonary thromboendarterectomy (PTE) for CTEPH
Indications
PTE is the standard treatment in symptomatic patients with chronic thromboembolic pulmonary hypertension with surgically accessible disease. They should be evaluated at a center with significant experience in the procedure.
The following criteria should be met:
- NYHA class III-IV symptoms
- Preoperative PVR >300 dynesxsecxcm-5
- Surgically accessible thrombi in the main, left/right, lobar, segmental, or subsegmental arteries
- Comorbidities that are not prohibitive for surgical correction and recovery
There are four types of pulmonary occlusive disease:
- Type I. Visible clot in the main branch PA
- Type II. Organized thrombus in the lobar branches; most frequent (40-70%)
- Type III. Obstructive disease at the segmental level
- Type IV. Disease limited to the subsegmental branches
Surgical technique
The procedure is performed via median sternotomy using central bicaval cannulation and venting through the right superior pulmonary vein and aortic root. Aortic cross clamp and standard cardioplegia are employed. Deep hypothermic circulatory arrest (18°C) is mandatory to eliminate back-bleeding from the robust bronchial collateral flow and improves visualization of the distal pulmonary branches during the endarterectomy. The SVC is mobilized circumferentially to the azygous vein. The SVC is retracted laterally and the aorta medially to expose the right PA, which is opened longitudinally. The endarterectomy is then undertaken by entering the proper plane between organized thrombus and normal intima. The proper plane is indicated by the presence of a pearly white layer. Using the “hand-over-hand” technique, gentle traction on the endarterectomy specimen while sweeping away the wall of the pulmonary artery often permits separation of the organized thrombus and vessel wall. The endarterectomy should be carried into each sub-segmental branch individually. The left PA is approached via an incision of the distal main PA into the left PA to the pericardial reflection. Once complete, the patient is re-warmed, the pulmonary arteriotomy repaired, and the patient separated from CPB.
Postoperative Care and Complications
Patients should remain mechanically ventilated with relatively higher tidal volumes to encourage recruitment of the lower lobes which may receive a disproportionate amount of the pulmonary blood flow. Anticoagulation must be initiated as soon as it is safe from a perioperative bleeding perspective. These patients will require anticoagulation for life. Despite right ventricular dysfunction preoperatively, after a successful endarterectomy, significant right ventricular support is rarely required. Pulmonary hemorrhage is a rare but life threatening complication resulting from full thickness injury often at the subsegmental level. Emergent bronchoscopy to identify the side of hemorrhage, followed by insertion of a double lumen endotracheal tube to isolate to non-hemorrhaging lung. Catheter based embolization is typically required, often with ECMO support. Reperfusion injury occurs in approximately 10% of patients and is associated with desaturation and presence of edema-like fluid in the airways. Treatment is supportive with careful management of ventilation, and aggressive diuresis.
In experienced centers, mortality rate has been reported to be as low as 5%. Inadequate reduction in PVR is the biggest risk factor for mortality. Long term survival following pulmonary endarterectomy is excellent, with preservation in the reduction of pulmonary artery pressures.
Suggested Readings
- Jamieson SW, Kapalanski DP: Pulmonary endarterectomy. Curr Probl Surg 2000; 37(3):165–252.
- Madani, M. Surgical Treatment of Chronic Thromboembolic Pulmonary Hypertension: Pulmonary Thromboendarterectomy. Methodist Debakey Cardiovasc J. 2016;12(4):213-218.
- Critical Care of Patients after Pulmonary Thromboendarterectomy. J Cardiothorac Vasc Anesth. 2019; 33(11):3110-3126.
