OVERVIEW
Pulmonary embolism (PE), is a clinical and pathophysiologic syndrome of impaired pulmonary circulation due to blockage of the main trunk or branches of the pulmonary artery by endogenous or exogenous emboli. It includes pulmonary thromboembolism, fat embolism syndrome, amniotic fluid embolism, air embolism, and tumor embolism. Among them, pulmonary thromboembolism (PTE) is the most common type of PE, which refers to the disease caused by thrombus from the venous system or the right heart obstructing the pulmonary artery or its branches, with pulmonary circulation and respiratory dysfunction as the main clinical manifestations and pathophysiological features, and accounts for the majority of PE, which is usually referred to as PTE.
If lung tissue necrosis occurs further on the basis of pulmonary embolism, it is called pulmonary infarction (pulmonary infarction).
Causes
(i) Main causes
Thrombus is the most common pulmonary embolus. 70% to 95% is due to the dislodgment of deep vein thrombus into the pulmonary artery and its branches with the blood circulation. The primary site is mainly the deep veins of the lower limbs. Other emboli: e.g. with fat embolism, air embolism, amniotic fluid, bone marrow, parasites, placental trophoblast, metastatic carcinoma, bacterial embolism, cardiac redundancy can be caused. The conditions for venous thrombosis are stagnant blood flow, damage to the walls of the venous vasculature and hypercoagulability.
(II) High risk factors
1. Age factor
Autopsy data show that PE occurs at the age of 50-65 years old, and the prevalence of children is about 3%, while the prevalence of children over 60 years old can be up to 20%. The prevalence of PE in children is about 3%, and that of children over 60 years old can be up to 20%. 90% of the fatal PE occurs at the age of 50 years old or above. The incidence of DVT in women aged 20-39 is 10 times higher than that in men of the same age.
2. Reduced activity
Long-term inappropriate bed rest due to lower limb fracture, paralysis, severe cardiopulmonary disease, surgery, etc., or reduction of limb activity in healthy people reduces the driving force of venous blood flow, leading to stagnation of blood flow and DVT formation.
3. Varicose veins and thrombophlebitis
Pulmonary arteriography and lung perfusion scanning show that 51% to 71% of people with lower extremity deep vein thrombosis may combine with PE. due to varicose veins and deep vein thrombophlebitis patients, due to a variety of reasons, once the pressure inside the vein rises sharply or the venous blood flow increases suddenly, the embolus dislodges and PE occurs.
4. Cardiopulmonary diseases
25%～50% of PE patients have cardiopulmonary diseases, especially patients with atrial fibrillation and heart failure are most likely to occur.
5. Trauma
PE occurs in 15% of trauma patients, among which tibial, pelvic and spinal fractures are often prone to PE; in addition, soft tissue injuries and extensive burns can also be complicated by PE, which may be caused by the release of certain substances from the injured tissues, which may damage the endothelial cells of the pulmonary vasculature or result in hypercoagulable state.
6.Tumor
Many tumors such as pancreatic cancer, lung cancer, colon cancer, gastric cancer and osteosarcoma can be combined with PE.
7. Pregnancy and contraceptive pills
The incidence of venous thrombosis in women taking birth control pills is 4-7 times higher than that in those not taking the pills. It has been reported that PE can also be induced by intravenous infusion of estrogen.
8. Other causes
Obesity, certain blood diseases, diabetes mellitus, pulmonary cysticercosis, and so on.
Symptoms
PE lacks specific clinical symptoms and signs, which makes the diagnosis difficult and easy to be missed.
1. Symptoms
Symptoms of PE lack specificity. Symptoms depend on the size and number of emboli, the location of embolism and whether the patient has underlying diseases of the heart, lungs and other organs. Most patients are suspected of having PE because of dyspnea, chest pain, syncope, syncope and/or hemoptysis. chest pain is a common symptom of PE, which is mostly caused by pleural irritation due to distal PE. However, it should be differentiated from chest pain caused by acute coronary syndromes (ACS) or aortic coarctation. In patients with pre-existing heart failure or lung disease, increased dyspnea may be the only symptom of PE. Hemoptysis, suggestive of pulmonary infarction, most often occurs within 24 h of pulmonary infarction and is bright red, or may be dark red if it occurs within a few days. Syncope, although uncommon, is sometimes the only or first symptom of acute PE, which may be completely asymptomatic, but is only discovered accidentally during the diagnosis of other diseases or autopsy.
2. Physical signs
The main signs are respiratory and circulatory, especially increased respiratory rate (more than 20 breaths/minute), increased heart rate (more than 90 beats/minute), decreased blood pressure and cyanosis. Hypotension and shock are rare but important.
Examination
1. Arterial blood gas analysis
Arterial blood gas analysis is a nonspecific test for hypoxemia, hypocapnia, increased alveolar-arterial oxygen gradient [P(A-a)O2], and respiratory alkalosis, but as many as 40% of patients have normal arterial oxygen saturation and 20% have normal alveolar-arterial oxygen gradient.
2. Plasma D-dimer
In acute thrombosis, the simultaneous activation of coagulation and fibrinolysis can cause an increase in plasma D-dimer levels.The negative predictive value of D-dimer assay is very high, and the positive predictive value is very low. Therefore, the main value of plasma D-dimer assay is to exclude acute PE, but not to confirm the diagnosis of PE.
3. Electrocardiogram
The electrocardiographic manifestations of acute PE are nonspecific. Incomplete or complete right bundle branch block. Mild cases may present only with sinus tachycardia, seen in about 40% of patients. Atrial arrhythmias, especially atrial fibrillation, are also common.
4. Echocardiography
Echocardiography is valuable in suggesting diagnosis, assessing prognosis and excluding other cardiovascular diseases.
5. Chest X-ray
If PE causes pulmonary hypertension or pulmonary infarction, X-ray film may show signs of pulmonary ischemia, such as sparse and thin pulmonary texture, protruding or aneurysmal dilatation of pulmonary arterial segments, widening of the right lower pulmonary artery trunk or accompanied by truncation signs, and signs of right ventricular enlargement.
6.CT pulmonary arteriography
CT can visually determine the degree and shape of pulmonary embolism, as well as the site and scope of involvement, and is an important noninvasive examination technique for diagnosing PE, but its sensitivity to subsegmental and distant pulmonary artery thrombus is poor. Combined CT venography and pulmonary arteriography can enhance the sensitivity of PE diagnosis. However, CT venography significantly increases the radiation dose and should be used with caution in young women. Compression venous ultrasonography (CUS) has similar diagnostic value to CT venography in patients with DVT (deep vein thrombosis), and it is recommended that ultrasound be used instead of CT venography.
7. Radionuclide pulmonary ventilation-perfusion scanning
The typical sign is a perfusion defect in the distribution of lung segments that does not match the ventilation image, which is of special significance in the diagnosis of PE beyond the subsegment. However, any factors causing impaired pulmonary blood flow or ventilation, such as lung inflammation, lung tumors, chronic obstructive pulmonary disease, etc., can cause local ventilation and blood flow disorders, so this test alone may cause misdiagnosis, this test can be performed at the same time with the venous imaging of the lower extremities, combined with chest X-ray film, CT pulmonary arteriography, can significantly improve the diagnostic specificity and sensitivity.
8. Magnetic resonance pulmonary angiography (MRPA)
MRPA directly shows the low perfusion area caused by emboli and PE in the pulmonary artery. It has been recognized that this method has higher sensitivity and specificity for the diagnosis of thrombus in the pulmonary artery above the lung segment, and it is suitable for those who are allergic to iodine contrast agent.
9. Lower extremity deep vein examination
PE and DVT are different clinical manifestations of VTE, 90% of PE patients have emboli originating from lower extremity DVT, and 70% of PE patients are combined with DVT.Due to the close relationship between PE and DVT, and the easy operation of lower extremity venous ultrasound, lower extremity venous ultrasound has some value in PE diagnosis. In addition to routine lower extremity venous ultrasound, CUS is recommended for suspected patients, and the failure of the vein to be compressed or the absence of blood flow signal in the venous lumen are specific signs of DVT.
Diagnosis
PE is not only nonspecific in clinical presentation, but also lacks specificity in routine investigations such as chest radiograph, electrocardiogram, blood gas analysis, and echocardiography. Multi-row spiral CT, radionuclide lung ventilation perfusion scanning, and pulmonary arteriography can often clarify the diagnosis, but the cost is high. Taking into account the actual situation in China, we recommend adopting a “three-step” strategy for patients suspected of acute PE, which includes firstly assessing the clinical likelihood, then performing the initial risk stratification, and then selecting the examination means step by step to clarify the diagnosis.
1. Clinical probability assessment
The clinical likelihood of the patient is evaluated based on past medical history, heart rate, and other symptoms, and the likelihood of PE is assessed.
2. Initial risk stratification
Initial risk stratification of the severity of acute PE is performed to assess the risk of early death from PE. Patients can be categorized into high-risk PE and non-high-risk PE based on their current clinical status, and this stratification is important for both diagnosis and treatment strategy, which determines the next step in the diagnostic and therapeutic process.
(1) Suspected PE with shock or hypotension is suspected high-risk PE, which is life-threatening at any time, and CT pulmonary arteriography is preferred for definitive diagnosis. If the patient and the hospital are unable to perform CT pulmonary arteriography, bedside echocardiography is preferred to find evidence of acute pulmonary hypertension and right ventricular dysfunction.
(2) Suspected PE without shock or hypotension is a non-high-risk PE, which is first evaluated for clinical probability, and the next diagnostic strategy is decided on the basis of this evaluation.
Differential diagnosis
Diseases that should be differentiated from pulmonary embolism and pulmonary infarction include acute myocardial infarction, coronary artery insufficiency, pneumonia, pleurisy, pulmonary atelectasis, asthma, entrapment aneurysm, primary pulmonary hypertension and dysthymia.
Treatment
In high-risk PE patients, reperfusion therapy is rapidly initiated once the diagnosis is confirmed.
Non-high-risk patients are categorized into intermediate-risk and low-risk patients based on their clinical symptoms. Patients with right ventricular dysfunction confirmed by echocardiography or CT angiography with elevated troponin, a biomarker of myocardial injury, are considered intermediate- to high-risk, and these patients should be closely monitored for early detection of hemodynamic derangement and initiation of remedial reperfusion therapy as soon as it occurs. Those with normal right ventricular function and/or cardiac markers are at low to moderate risk.
1. Hemodynamic and respiratory support
Acute right heart failure and its resulting lack of cardiac output is the leading cause of death in patients with PE. Therefore, supportive therapy for patients with PE combined with right heart failure is extremely important. In patients with PE who have a low cardiac index and normal blood pressure, administration of a moderate fluid shock (500 mL) can help increase cardiac output.
Pressure-boosting agents are usually required along with pharmacologic, surgical, or interventional reperfusion therapy. e.g., norepinephrine, but should be limited to hypotensive patients. Dobutamine and/or dobutamine are beneficial in PE patients with low cardiac index and normal blood pressure, but should be scaled. Epinephrine combines the advantages of norepinephrine and dobutamine without the vasodilator effect of the body circulation and may be beneficial in patients with PE with shock.
Vasodilators reduce pulmonary arterial pressure and pulmonary vascular resistance, but these drugs lack pulmonary vascular specificity and may lead to further reduction of blood pressure in the body circulation after administration via the body circulation and should be used with caution.
Patients with PE often have moderate hypoxemia and hypocapnia. It is usually reversed after oxygenation, so mechanical ventilation should be performed.
2. Anticoagulation
Anticoagulation is recommended for patients with acute PE to prevent early death and recurrence of VTE (venous thromboembolism).
(1) Parenteral anticoagulants Parenteral anticoagulants should be given to patients with a high or moderate clinical likelihood of PE while awaiting diagnostic results. The parenteral anticoagulants normal heparin, low molecular weight heparin, or sodium sulfadiazine heparin have an immediate anticoagulant effect but should be used according to the patient’s clinical presentation.
(2) Oral anticoagulants Oral anticoagulants should be given to patients with acute PE as early as possible, preferably on the same day as parenteral anticoagulants. Commonly used oral anticoagulants are: warfarin, nitrobenzylacetone coumarin, phenylpropylcoumarin, phenindione, etc., of which warfarin is most commonly used in China.
3. Thrombolytic therapy
(1) Commonly used drugs Thrombolytic drugs commonly used in our clinic are urokinase (UK) and recombinant tissue-type fibrinogen activator alteplase (rt-PA).
(2) Contraindications ①Absolute contraindications Hemorrhagic stroke; ischemic stroke within 6 months; central nervous system injury or tumor; major trauma, surgery, or head injury within the past 3 weeks. Relative contraindications: transient ischemic attack within 6 months; oral anticoagulant application; pregnancy, or 1 week after delivery; recent cardiopulmonary resuscitation.
(3) Thrombolytic time window Thrombolytic therapy can be started within 48 hours of the onset of acute PE to achieve maximum efficacy, but for those patients with symptomatic acute PE, thrombolytic therapy within 6 to 14 days still has a role.
4. Surgical thrombectomy
5. Percutaneous catheter intervention
Interventional therapy can remove the thrombus in the pulmonary artery and its main branches, promote the recovery of right ventricular function, and improve the symptoms and survival rate.
6. Venous filters
Routine implantation of inferior vena cava filters in patients with PE is not recommended (III, A). Venous filter implantation is an option in patients with PE who have absolute contraindications to anticoagulant medications and who have relapsed after receiving anticoagulant therapy of adequate intensity (IIa, C).
7. Early discharge and home treatment
Patients with acute PE at low risk of adverse events can be discharged early and treated out of hospital.