Advances in the diagnosis and treatment of pulmonary embolism
Pulmonary embolism (PEA) is a disorder caused by an embolic material embedded in the pulmonary artery and its branches via a vein, blocking the blood supply to the tissue. The common embolus is a thrombus, the rest are rare neoplastic cells, fat droplets, air bubbles, intravenous drug particles, and occasionally pulmonary vascular blockage caused by the tip of an indwelling catheter. Most pulmonary emboli do not necessarily cause pulmonary infarction because the lung tissue receives a dual blood supply from the bronchial arteries and pulmonary arteries and because direct gas exchange between the lung tissue and alveoli is also possible.
Epidemiology
The incidence of pulmonary embolism abroad is high, reaching 600,000 per year in the United States alone. About one-tenth of them die within one hour, and the remaining one-third still die, accounting for the third leading cause of death in the population. A decreasing trend in incidence has also been reported in recent years with the increase in adults receiving anticoagulation therapy. No exact epidemiological data are available in China, but among more than 900 autopsies of cardiopulmonary vascular disease reported by Fu Wai Hospital, 100 cases (11%) of large thrombotic occlusion above the pulmonary segment were reported, accounting for 29% of autopsies of wind heart disease, 26% of cardiomyopathy, and 19% of pulmonary heart disease, indicating that cardiopulmonary vascular disease is also often complicated by pulmonary embolism.
Etiology and pathogenesis
1.Thrombosis
Pulmonary embolism is often a comorbidity of venous thrombosis. The emboli usually originate from the deep veins of the lower extremities and pelvis, and a few from the veins of the upper extremities, head and neck, and enter the pulmonary artery through circulation to cause embolism. Stagnant blood flow, increased blood coagulability and venous endothelial damage are the contributing factors to thrombosis. Therefore, trauma, prolonged bed rest, varicose veins, intravenous cannulation, pelvic and hip surgery, obesity, diabetes, contraceptive pills or other causes of hypercoagulability predispose to venous thrombosis. The early formed thrombus is fragile, and with the action of fibrinolytic system, it can easily fall off into the venous system and flow into the pulmonary circulation. Therefore, the risk of embolism is highest in the first few days of thrombosis.
2.Heart disease
It is the most common cause of pulmonary embolism in China, accounting for 40%. It involves almost all kinds of heart disease, and the incidence of pulmonary embolism is higher in those with combined atrial fibrillation, heart failure and subacute bacterial endocarditis. Right ventricular thrombus is the most common, with a few originating from the venous system. In addition to subacute bacterial endocarditis, bacterial emboli can also be caused by pacemaker infection. The former infectious emboli mainly come from the tricuspid valve. Occasionally, mitral redundancy in patients with precordial disease may enter the right heart from the left heart via the defective shunt and reach the pulmonary artery.
3.Tumor
In our country is the second cause, accounting for 35%, much higher than the foreign 6%. Lung cancer, digestive system tumor, choriocarcinoma, leukemia, etc. are more common. Only about 1/3 of malignant tumor complicating embolism is tumor embolism, the rest are thrombus. It is speculated that thrombokinase (thromoboplastin) and other substances that can activate the coagulation system, such as histone, tissue protease and protein hydrolase, may exist in the blood of tumor patients, so the incidence of pulmonary embolism in tumor patients is high, and it may even be their early symptoms.
4.Pregnancy and childbirth
The incidence of pulmonary embolism in pregnant women is several times higher than that in age-matched non-pregnant women, and the incidence is highest in postpartum and post-cesarean section. The increased intra-abdominal pressure during pregnancy, hormonal relaxation of vascular smooth muscle, pelvic vein compression causing slow venous blood flow and changing the rheological properties of blood are all likely to aggravate venous thrombosis. In addition, there is an increase in coagulation factors and platelets and a decrease in the activity of the plasminogen-plasmin proteolytic system. However, there is no absolute difference between these changes and those in pregnant women without thromboembolism. Amniotic fluid embolism is also a serious complication during labor.
5. Other
Other rare causes are fat embolism due to long bone fractures, air embolism due to accidents and decompression sickness, parasitic and foreign body embolism. In the absence of obvious contributing factors, a decrease in hereditary anticoagulation factors or an increase in fibrinolytic plasminogen activator inhibitors should also be considered.
Pathology
Most acute pulmonary embolisms may involve multiple pulmonary arteries. In terms of embolism site, the right lung is more often involved than the left, and the lower lobe more often than the upper lobe, but rarely embolism is seen in the right or left pulmonary artery trunk or riding across the pulmonary artery bifurcation. When thromboemboli are poorly mechanized, they tend to form fragments in the pathway through the heart to embolize small vessels. If the fibrinolytic mechanism cannot completely dissolve the thrombus, the surface of the embolus is gradually covered by endothelial-like cells after 24 hours and firmly adheres to the arterial wall after 2 to 3 weeks, and the vessel is revascularized. Early embolus regression, the flushing effect of blood flow recanalization, the fibrin and platelet agglutination covering the surface of the embolus and the thrombolytic process can produce new emboli to further embolize small vascular branches. Whether an embolus causes pulmonary infarction is determined by the size of the involved vessel, the extent of the embolism, the ability of the bronchial artery to supply blood flow, and the adequacy of ventilation in the obstructed area. The histological features of pulmonary infarction are intra-alveolar hemorrhage and alveolar wall necrosis, with little inflammation found. Cavitation is rarely produced when there is no original pulmonary infection or when the emboli are noninfectious. Decreased pulmonary surface active material in the infarcted area can lead to pulmonary atelectasis. Exudation from the pleural surface is common and 1/3 is hemorrhagic. If it survives, the infarcted area eventually forms a scar.
Pathophysiology
The physiologic impact of pulmonary embolism depends on three factors.
1, the nature of the embolus, the size of the involved vessels and the extent of obstruction of the pulmonary vascular bed.
2, the mediators such as 5-hydroxytryptamine and histamine released by the embolus after embedding in the pulmonary vasculature.
3, the patient’s original cardiopulmonary function status.
The immediate effect of pulmonary embolism on whistling is an increase in the dead space/tidal ratio, followed by stimulation in the lung and stimulation of J receptors causing reflex shallow and rapid whistling, further increasing dead space ventilation. PaCO2 is normalized or reduced due to the compensatory effect of the increased number of whistles.
Pulmonary embolism does not directly affect the partial pressure of arterial blood oxygen. However, edema and pulmonary atelectasis in the area near the pulmonary embolism can affect diffusion function, reduce the ventilation/flow ratio, and lower the arterial partial pressure of oxygen. If, at the same time, there is a decrease in pulmonary surface active substance, alveolar atrophy and alveolar fluid retention can further aggravate hypoxemia and it is difficult to correct by oxygenation. These changes are further exacerbated in patients with pre-existing cardiopulmonary disease. CO2 retention may also occur in those with neuromuscular disorders, severe pleural pain, and the presence of whistling muscle fatigue.
The hemodynamic effects of pulmonary embolism are more complex. In the absence of cardiopulmonary disease, pulmonary hypertension develops only after more than half of the pulmonary vascular structures have been affected by the embolus. However, in patients with significant abnormalities in pulmonary vascular resistance that existed prior to embolization, a relatively small number of emboli is sufficient to trigger pulmonary hypertension. Vasoactive substances released after pulmonary embolism, such as 5-hydroxytryptamine, promote the development of pulmonary hypertension. The application of 5-hydroxytryptamine antagonists significantly attenuates or even blocks the adverse hemodynamic effects of pulmonary embolism and its effect on bronchoconstriction.
Clinical manifestations
The clinical manifestations of pulmonary embolism are related to the extent of the involved pulmonary artery, the presence of pulmonary infarction and the underlying disease. A small pulmonary embolism may be asymptomatic or only anxious. In large pulmonary artery embolism or extensive pulmonary vascular bed involvement, pallor, weakness, cold sweat, nausea, vomiting, oliguria, palpitation and difficulty in whistling may be manifested. On examination, cyanosis, shallow and rapid whistling, pulmonary wet rales or rales, pulmonary vascular murmurs, tachycardia, P2 hyperactivity, decreased arterial blood pressure and even signs of shock and pulmonary heart disease are seen.
After the appearance of pulmonary infarction, the patient may have sudden onset of chest pain, dyspnea and hemoptysis. In addition, a small number of patients have high fever early on, and about 40% of patients have low to moderate fever. Depending on the location of the infarction, the chest pain may be severe and confined to the ribs or may radiate to the shoulder or abdomen, similar to a myocardial infarction, but cannot be relieved by nitroglycerin. On examination, pleural friction sounds may be heard, or signs of pleural effusion may be found.
Diagnosis and differential diagnosis
Approximately 11% of patients with pulmonary embolism die within 1 hour of onset. Only 29% of the remaining patients can be diagnosed definitively, with a mortality rate of 8%, while the mortality rate in patients without a definitive diagnosis is as high as 30%. Therefore, early detection is very important and can improve the success rate of resuscitation.
The diagnosis of pulmonary embolism relies heavily on the vigilance of the clinician. The possibility of pulmonary embolism should be considered in patients with slow venous flow with unexplained dysphonia. Other aggravating factors are oral contraceptives, prolonged bed rest, congestive heart failure, surgical procedures, etc.
Tests that are informative for the diagnosis of pulmonary embolism include elevated serum LDH, decreased PaO2, widened PA-aO2, and ECG showing ST-segment and T-wave changes similar to myocardial infarction and/or P-wave and QRS waveforms similar to acute pulmonary heart disease.
X-rays showing patchy infiltrates, pulmonary atelectasis, diaphragmatic elevation, pleural effusion, especially round dense shadows with pleura-based convexity toward the hilum (Hamptom’s hump) and dilated pulmonary arteries with sparse distal lung texture (Westermark’s sign) are of great value for the diagnosis of pulmonary embolism. Nuclide lung ventilation/perfusion scan is the most sensitive noninvasive method for the diagnosis of pulmonary embolism. Although the specificity is low, a typical multiple, segmental or wedge-shaped perfusion defect with normal or increased ventilation can be established in combination with clinical and diagnosis.
Pulmonary arteriography is the most specific method for the diagnosis of pulmonary embolism and is indicated in cases where clinical and nuclear scans are suspicious and where surgical treatment is required. It presents as a filling defect, arterial truncation or “pruning sign”. Small vessels ≤2 mm in diameter cannot be visualized on imaging, so multiple small emboli are often missed. Magnetic resonance is a useful noninvasive technique for the diagnosis of pulmonary embolism, and in the case of larger emboli, a significant filling defect of the pulmonary artery can be seen.
Easy to be confused with pulmonary embolism are pneumonia, pleurisy, pneumothorax, slow-onset lung, lung tumor, acute myocardial infarction, congestive heart failure, cholecystitis, pancreatitis, etc. Isotope, CT and MRI help to differentiate.
Treatment
I. Symptomatic treatment
Including improvement of hypoxemia, pain relief, bronchodilation, correction of shock and heart failure, etc.
II. Specific treatment
1.Anticoagulation
For hemodynamically stable patients, intravenous heparin therapy and intravenous heparin combined with oral anticoagulation therapy are given successively for 4 to 5 days each, and then switched to oral anticoagulation therapy, which is maintained for 3 months.
2.Thrombolysis
For hemodynamically unstable patients, thrombolytic therapy with urokinase or rt-PA should be used first, and then switched to anticoagulation therapy for maintenance after it is effective. Urokinase (UK): loading dose 4 400 IU/kg, iv 10 min, followed by 2 200 IU.kg-1.h-1 for 12 h; or 20 000 IU/kg continuous drip for 2 h. rt-PA 50-100.
After effective treatment, measures should be taken to prevent re-embolization. This can be done by ligation, placement of a special clip or inferior vena cava filter. The first two methods have been gradually abandoned due to many complications. Recently, the application of the filter has significantly improved the effect, which can reduce the incidence of pulmonary embolism to less than 2.4%.
3.Surgery
Broadly speaking, surgical treatment includes two methods of interventional radiology or surgical treatment. Interventional radiology surgery is to crush or remove the embolus by using different functional catheters according to the requirements. This technique is not suitable for patients with unclosed foramen ovale, because the embolus may be dislodged and flow into the left heart, causing embolism in the body circulation.
Surgical embolization is indicated for large pulmonary artery embolism, which can rapidly restore pulmonary blood supply and improve hemodynamic abnormalities. However, the mortality rate can be as high as 30-44%, so it is often reserved for patients in whom thrombolytic therapy is ineffective or contraindicated for thrombolytic therapy.
4.Prevention of re-embolism
Other preventive measures are to reduce or avoid various factors of thrombosis, such as reducing blood pooling in the veins, correcting hypercoagulability and avoiding endothelial damage. Those who have formed thrombus should be treated as early as possible to prevent the embolus from flowing into the vena cava and entering the pulmonary circulation.
5.Caution
In anticoagulation and tethering therapy, care should be taken to avoid contraindications, such as active bleeding, bleeding tendency and bacterial endocarditis. In addition, coagulation function should be closely monitored during treatment to prevent and treat complications such as cerebral hemorrhage.