Pulmonary embolism (PE) is a clinical and pathological syndrome of impaired pulmonary circulation caused by an embolus entering and blocking the pulmonary artery or its branches, blocking the blood supply to the tissues. The common embolus is thrombus, and other thrombi such as neoplastic cells, fat, air bubbles, and intravenous input of drug particles PE is mainly from deep venous thrombosis (DVT), and PE is the most common and important complication of DVT. The incidence and high incidence of pulmonary embolism abroad, the United States each year about 600,000 people, 1/3 of the deaths. There is no exact epidemiological information in China yet. In 90 autopsies of cardiopulmonary vascular disease in Fu Wai Hospital, there were 100 cases (11%) of large thrombotic blockage above the lung segment, accounting for 29% of wind heart disease, 26% of cardiomyopathy and 19% of pulmonary heart. Data from Anzhen Hospital show that the number of PE patients has increased significantly in recent years (Figure 1). 19.2% of PE patients die, of which 77.8% are untreated and 7.0% are treated. The 2-, 3-, 5-, and 10-year survival rates of patients with thromboembolic pulmonary hypertension were 95.8%, 91.6%, 71.3%, and 46.2%, respectively.
Etiology and pathogenesis
1. Thrombosis: Pulmonary embolism is usually a comorbidity of venous thrombosis. The emboli usually originate from the deep veins of the lower extremities and pelvis and cause embolism through circulation to the pulmonary arteries. Rarely, they originate from the veins of the upper extremities, head and neck. Stagnant blood flow, increased blood coagulability and venous endothelial injury are contributing factors to thrombosis. Trauma, long-term bed rest, varicose veins, intravenous cannulation, pelvic surgery, obesity, diabetes, etc. are likely to induce venous thrombosis, and the risk of pulmonary embolism is highest in the first few days of thrombosis because the thrombus is fragile in the early stage.
2, heart disease: it is the most common cause of pulmonary embolism in China, accounting for 40%, and the incidence is higher in those with combined atrial fibrillation, heart failure and subacute bacterial endocarditis. Right heart cavity thrombus is common, and infected emboli mainly come from tricuspid valve, occasionally from mitral valve.
3, tumor: about 35%, the second cause, compared with 6% abroad. Among them, lung cancer, digestive tumor, choriocarcinoma and leukemia are more common, 1/3 are tumor emboli and 2/3 are thrombi. As the blood of tumor patients may have thrombokinase and other substances that can activate the coagulation system such as histone, tissue protease, protein hydrolase, etc.
4. Pregnancy and childbirth: Pulmonary embolism has the highest incidence in pregnant women several times more often than in age-matched non-pregnant women, after delivery and after cesarean section. Increased intra-abdominal pressure and hormonal relaxation of vascular smooth muscle and pelvic vein compression during pregnancy cause slow venous blood flow and change the rheological properties of blood, which aggravates venous thrombosis. This is accompanied by an increase in coagulation factors and platelets and a decrease in the activity of the plasminogen-plasmin proteolytic system. And amniotic fluid embolism is also a serious complication during labor.
5.Other: such as fat embolism due to long bone fracture, air embolism due to accident and decompression sickness, parasite and foreign body embolism, etc.
Pathophysiological changes
Most acute pulmonary embolism can involve multiple pulmonary arteries, and the site of embolism is more in the right than in the left lung, and more in the lower than in the upper lobe, but it is rare to see embolism in the right or left pulmonary artery trunk or riding across the bifurcation of pulmonary artery. When the thromboembolus is poorly mechanized, it tends to form fragments in the small vessels through the cardiac pathway. If the fibrinolytic mechanism cannot completely dissolve the thrombus, the surface of the embolus will be gradually covered by endothelial cells after 24h, and will be firmly adhered to the vessel wall after 2 to 3 weeks. Early embolus retreat, the flushing effect of blood flow recirculation, the fibrin and platelet coagulation covering the surface of the embolus and the thrombolytic process can produce new embolus to further embolize the small vessel branches. Whether an embolus causes pulmonary embolism is determined by the size of the involved vessel, the extent of obstruction, the ability of the bronchial artery to supply blood flow, and the appropriateness of coarctation in the obstruction area. The histologic features of pulmonary embolism are intra-alveolar hemorrhage and alveolar wall necrosis, but inflammation is rarely found, and cavitation is rarely produced when there is no original pulmonary infection or the embolus is noninfectious. Loss of lung surface active material in the embolic area can lead to pulmonary atelectasis, and exudate is common on the pleural surface, 1/3 of which is hemorrhagic. Patients who survive eventually form a scar in the embolized area.
PE mainly affects cardiopulmonary function and vascular endothelial function, and the degree of impact depends on the presence of previous cardiopulmonary vascular knockdown function and the extent and speed of pulmonary artery occlusion. after PE occurs, the pulmonary vascular endothelium is damaged, releasing a large amount of contractile substances; when thrombus is formed, fresh thrombus contains a large number of platelets and thrombin; when the embolus moves within the pulmonary vasculature, platelet activation degranulation, releasing a large amount of vasoactive substances that leads to extensive constriction of small pulmonary arteries, reflexively causing sympathetic release of catecholamines and forming the first malignant loop at the pulmonary vasculature. The concentration of endothelin in the circulation is significantly increased, and the amount of local endothelin in the coronary arteries is also increased, leading to coronary artery spasm, resulting in insufficient coronary perfusion and myocardial ischemia, forming a second malignant loop at the coronary arteries of the heart. Several of these changes often coexist and interact with each other, and if not treated promptly, a lethal malignant loop can be formed.
PE causes pulmonary ventilation/perfusion (V/Q) dysregulation, which in severe cases leads to a significant increase in intrapulmonary shunts, elevated right atrial pressure, and patent foramen ovale. It causes reflex bronchospasm when the area is large; chemical mediators such as 5-hydroxytryptamine, thromboxane A2, and histamine can cause changes in vascular permeability; when pulmonary capillary blood flow is severely reduced or terminated for 24 h, alveolar surface active substances are reduced and pulmonary atelectasis occurs; alveolar epithelial permeability increases and a large number of inflammatory mediators are released, causing local or even diffuse pulmonary edema, pulmonary hemorrhage, and alveolar cell function and pulmonary ventilation- Diffusion function is further reduced.
Clinical features
The symptoms of pulmonary embolism can range from none to sudden death. The common symptoms are dyspnea and chest pain, both of which occur in more than 80% of cases. Pleural pain is caused by inflammation of the adjacent pleural fibrin and is often suggestive of pulmonary infarction when it occurs suddenly. Diaphragmatic pleural involvement may radiate to the shoulder or abdomen. If there is retrosternal pain, it resembles myocardial infarction. Chronic pulmonary embolism may be associated with hemoptysis. Other symptoms are anxiety, possibly due to pain or hypoxemia. Syncope is often a sign of pulmonary infarction, caused by inadequate blood supply to the brain due to massive PE, and is one of the earliest symptoms of pulmonary hypertension in chronic pulmonary embolism. Dyspnea, chest pain, and hemoptysis are the triad of signs typical of clinical pulmonary infarction and can be present in 1/3 of patients.
Common signs are increased respiration, cyanosis, pulmonary wet rales or croup, pulmonary vascular murmurs, pleural friction sounds or signs of pleural effusion. Circulatory signs include tachycardia, P2 hyperactivity and shock or corresponding manifestations of chronic pulmonary heart disease. About 40% of patients have low to moderate fever, and a few have high fever early.
Ancillary tests
D-Dimer (plasma D-dimer) is a cross-linked fibrin-specific degradation product with a high negative predictive value. Acute PE can be excluded by ELISA with a sensitivity of 100%, specificity of 26% and negative predictive value of 100% for PE.
Pulmonary vascular bed occlusion 15%-20% can show a decrease in partial pressure of oxygen, but normal PaO2 does not exclude PE, and alveolar-arterial partial pressure difference of oxygen (P(A-a)O2) and PaCO2 have higher sensitivity than PaO2.
ECG changes are sinus tachycardia with T-wave inversion and ST-segment drop. Typically, SⅠQⅢTⅢ type, i.e., deep S waves in lead I (>1.5 mm), deep Q and T wave inversions in lead III; V1-4 T wave inversions, similar to “coronal T” changes. The ECG before and after the onset of the disease should be carefully compared with the ECG before and after the onset of the disease for dynamic observation, and an 18-lead ECG examination should be done in patients with suspected PE.
Chest X-ray shows regional pulmonary vascular texture sparseness and slenderness, enhanced permeability of some lung fields, and Westermark sign. Patients with chronic pulmonary thromboembolism are seen with bulging pulmonary artery segments, dilated main pulmonary artery, widened right inferior pulmonary artery transverse diameter (>15 mm), sharp thinning of the anterior aspect of the dilated pulmonary artery, called Kunckle’s sign, and long enlarged right ventricle.
Transthoracic or transesophageal 2D echocardiography can directly or indirectly suggest the presence of PE, and attention should be paid to the right heart system in those suspected of PE. Echocardiography (UCG) is simple, rapid without reflex, does not require contrast, can be performed at the bedside in an emergency, and to some extent can be used as a means of risk grading, efficacy observation, and prognosis determination.
V/Q scans show sparse or absent radioactivity in lobes, segments, or multiple subsegments of the lung, while ventilation images are normal or near normal. Although 4% to 5% of those with normal V/Q lung scans still have subclinical PE, it is still one of the most valuable noninvasive methods for diagnosing PE.
Spiral CT is a newer and better method for the diagnosis of PE, which can directly show the 4th to 5th level branches of pulmonary vessels and has a sensitivity of 87% and specificity of 95% in identifying or excluding PE. Spiral CT-enhanced lung scan can determine the extent and degree of the lesion and the duration of the disease, and provide a basis for clinical selection of the correct treatment. direct signs of PE include “orbital sign” and eccentric filling defect. The “orbital sign” is a complete thrombotic occlusion of the lumen of the pulmonary artery with normal or widened diameter, or a non-occlusive intraluminal filling defect located in the center of the vessel, which is a direct sign of acute PE; the direct signs of chronic PE include eccentric and palpable filling defects of block-like tissue in the lumen of the pulmonary artery, and the presence of collateral vessels or vascular networks in areas of low pulmonary artery perfusion. Indirect signs of PE include limited uneven or sparse pulmonary vascular texture distribution, widened pulmonary arteries, pulmonary infarction, and small to moderate pleural effusion. However, it still has its limitations, is prone to false positives for pulmonary vessels below the segment, and spiral CT pulmonary angiography has shifted more from diagnosis to intervention.
Magnetic resonance angiography (MRA) can clearly show the 7-8 level branches of the pulmonary artery, and is one of the promising non-invasive examination methods.
Pulmonary angiography is the “gold standard” for the diagnosis of PE and has the ultimate diagnostic value, but its use is decreasing as other diagnostic methods become available, more often when other methods fail to confirm the diagnosis or when interventional treatment is needed.
Diagnostic strategy of PE
Clinical suspicion of PE (symptoms, signs)
ECG, X-ray chest film, blood gas abnormalities
D-Dimer: >500ug/L; <500ug/L, except acute PE
V/Q lung scan or spiral CT or MRA
①Venous examination of lower extremities: – Evaluation of deep veins
②Echocardiography: positive, indeterminate, negative, exclude PE
Pulmonary arteriogram: positive, confirm the diagnosis of PE
Treatment
1.General treatment: including absolute bed rest, oxygenation, anti-inflammation, pain relief, correction of shock and heart failure, etc.
2, Thrombolytic therapy: Thrombolytic therapy should be preferred for lobar or multi-pulmonary segment embolism, heavy clinical symptoms and obvious hemodynamic abnormalities, mainly for fresh thromboembolism within 2 weeks. Absolute contraindications to thrombolytic therapy include active internal bleeding, spontaneous internal bleeding, intracranial hemorrhage within 2 months, and post-cranial and spinal surgery; relative contraindications include major surgery within 10 days, ischemic stroke within 2 months, gastrointestinal bleeding within 10 days, severe trauma within 15 days, poorly controlled severe hypertension, recent cardiopulmonary resuscitation, platelets <100×109/L, pregnancy, bacterial endocarditis, and diabetic hemorrhagic retinopathy, etc.
The commonly used thrombolytic drugs are
①Urokinase (UK): it is the most commonly used in China, 1~1.5 million IU in 1/2~2h drops;
②Streptokinase (SK): 1~1.5 million IU in 1h (Dex 2.5~5mg is also used to prevent fever and chills);
③Recombinant tissue-type fibrinogen activator (rtPA): 10mg first, followed by 50mg in 1h, then 40mg in 2h;
④Single chain urokinase-type fibrinogen activator (SCUPA): 20mg, followed by 60mg for 1h;
⑤ Methoxyphenylated fibrinogen streptokinase complex (APSAC): 30mg in one push.
Heparin needs to be stopped when using UK and SK for thrombolysis. Anticoagulation therapy is routinely applied after thrombolysis, mostly with heparin and warfarin. APTT is measured every 4h, and heparin is started when it is less than 2 times the normal basal value. The loading dose of heparin is 2000-3000 IU/h, followed by 750-1000 IU/h or 15-20 IU/kg-1/h-1 maintenance, and the dose is adjusted according to APTT. Warfarin is added after 24-48 h of heparin application, and the two overlap until the INR is between 2 and 3 when heparin is discontinued. Generally, heparin is used for 7-10 days and warfarin for at least 3-6 months.
3.Interventional treatment: The indications include: acute massive PE with progressive hypotension, severe respiratory distress, shock, syncope, cardiac arrest, and those who are contraindicated for thrombolysis, those who are contraindicated for dissection, and those with extremely easy to dislodge lower vena cava or lower limb venous thrombosis
Commonly used interventions include
①Intracatheter thrombolysis: small doses of drugs in the pulmonary artery can reduce bleeding complications;
(ii) Guidewire-guided catheter thrombosis: pigtail catheter and Hydrolyser catheter can be used, the former is simple but ineffective, the latter is effective;
③Local mechanical dissipation: the application of specially designed mechanical thrombectomy device can crush the thrombus block to 13um particles, which is especially suitable for fatal PE, severe hypotension, and those with contraindications to thrombolysis, and is most suitable for central thrombus and has good effect on fresh thrombus;
④Vena cava filter implantation (IVC);
⑤ Combined application of catheter fragmentation and local thrombolysis;
⑥Other methods, such as balloon angioplasty, electrolysis, negative pressure suction embolization, etc.
4.Surgical treatment: mainly pulmonary artery thrombectomy: it is used for large PE with shock, systolic pressure <100mmHg, increased central venous pressure, renal failure, failure of medical treatment or inappropriate medical treatment.
For chronic PE, which can lead to embolic pulmonary hypertension, pulmonary thromboendarter cetomy (PTE) is often used with the following indications.
① Resting pulmonary vascular resistance > 30kPa・L-1・s-1;
②Pulmonary arteriography to determine the surgically accessible larger pulmonary artery thrombosis;
③ Cardiac function grade II-III;
④No contraindications for liver, kidney, brain, etc.
PTE can improve the hemodynamic status, prevent pulmonary edema caused by pulmonary hypertension and pulmonary reperfusion injury after thrombus stripping and prevention of postoperative re-embolism is the key to successful surgery, and postoperative anticoagulation therapy is warfarin for 6 months.