Pulmonary embolism (PE) is a syndrome of obstruction of pulmonary circulation caused by endogenous or exogenous emboli blocking the pulmonary arteries or their branches, resulting in corresponding clinical and pathophysiological changes, and is the most serious complication of obstetric venous thrombosis, leading to sudden death. The incidence of PE in pregnancy is 0.01%~0.04%, and the maternal mortality due to PE accounts for 50% of unexplained maternal deaths as reported abroad, and the mortality rate of untreated PE can be as high as 12.88%, while the mortality rate of treated patients is reduced to 0.7%. Therefore, early diagnosis and early prevention is the key.
[Etiology and pathogenesis].
High risk factors of PE during pregnancy and delivery ① Blood hypercoagulation state: except for Ⅺ and Ⅹ Ⅻ factors, all other coagulation factors increase during pregnancy, especially fibrinogen, prothrombin time and partial thromboplastin time are shortened, antithrombin Ⅲ level decreases, and thrombin production increases, and this physiological change continues until 2 weeks postpartum when it returns to normal. At the same time, euglobulin lysis time is prolonged, fibrinolysinogen is increased, and fibrinolytic activity is reduced until normalization 3-5 days after delivery. ②Stasis of blood flow: During pregnancy, the enlarged uterus compresses the iliac vein and inferior vena cava, causing obstruction of venous return and stasis of blood flow, causing damage to the endothelial cells of blood vessels and changes in the vessel wall, which easily leads to thrombosis. ③The effect of progesterone: progesterone can relax the smooth muscle of the vein, slow the blood flow, and stasis occurs in the inferior vena cava, which increases the possibility of deep vein thrombosis. ④ Local tissue damage during childbirth or surgery: the inner wall of blood vessels is easily damaged during childbirth and cesarean section, leading to an increased chance of venous embolism [1 ]. ⑤ Heart disease: In pregnant women with heart disease, especially when combined with atrial fibrillation or heart failure, emboli in the atria can be dislodged during pregnancy and delivery when hemodynamics change rapidly, leading to the occurrence of PE. (6) Other factors: postoperative bed rest, braking >3 days, weakened muscle contraction of the lower limbs, slow blood flow, as well as postoperative trauma repair, excessive coagulation mechanism and the use of anticoagulant drugs, all contribute to thrombus formation.
The pathophysiological changes caused by PE mainly include both hemodynamic and respiratory functions. The degree of cardiopulmonary function changes depends on the extent and speed of pulmonary artery occlusion, the status of the original cardiopulmonary function and the fibrinolytic activity of the pulmonary endothelium. In mild cases, there may be no significant changes, while in severe cases, it may lead to hypoxemia, hypocarbia, increased pulmonary circulatory resistance, pulmonary hypertension, acute pulmonary insufficiency and sudden death. ① Hemodynamic changes: when 50% of the vascular bed is blocked, pulmonary hypertension can occur; if there are serious cardiopulmonary disorders before embolization, the degree of pulmonary hypertension is more serious if the tolerance to PE is poor; neurohumoral factors can cause contraction of coronary arteries and other arterial vessels in addition to pulmonary artery contraction, to respiratory cardiac arrest. ② Changes in respiratory function: When PE occurs, alveolar dead space is enlarged, ventilation-perfusion malfunction occurs in the embolized area, and the non-perfused alveoli cannot carry out effective gas exchange; 5-hydroxytryptamine and histamine released from emboli can cause dead space and bronchospasm, which increases airway resistance and restricts ventilation. Current research indicates that PE is related to altered vascular endothelial function.
Clinical manifestations
PE is a serious complication of venous thrombosis. PE is a serious complication of venous thrombosis and can be fatal within a short period of time. 75% to 90% of the emboli in PE come from lower limb veins. The vast majority do not show any clinical signs and symptoms of DVT, and the risk of pulmonary infarction is much lower when signs and symptoms of DVT are present. In the early stages of lower extremity or pelvic vein thrombosis, the thrombus is easily dislodged and the embolus dislodged reaches the heart and lungs through the venous circulation, blocking the pulmonary vessels to form PE. clinical symptoms of PE vary in severity from transient shortness of breath to acute pulmonary heart disease with sudden dyspnea, cyanosis, right heart failure, and even sudden death. It mainly depends on the amount of pulmonary vascular blockage, the speed of occurrence and the underlying condition of the patient’s heart and lungs. The mean pulmonary artery pressure can be slightly increased in pulmonary vascular bed blockage >25%-30%; persistent pulmonary hypertension can occur in >50%; sudden death can occur in blockage up to 85%. Larger PE may cause bronchospasm alveolar surface active substance reduction, alveolar atrophy and pulmonary ventilation/flow ratio imbalance. Patients develop varying degrees of hypoxemia, hypocarbia and alkalemia.
The signs and symptoms of PE are nonspecific and the clinical manifestations are varied and related to the size and shape of the thrombus and the site and extent of blockage of the pulmonary vascular bed, depending mainly on the size of the blocked pulmonary artery and the number of lung segments. It is characterized by shallow and rapid breathing, especially after getting up and moving around or defecating. ② Chest pain: seen in 70% to 88% of cases, more common with blockage of large and middle pulmonary artery segments, often combined with peripheral vascular blockage. ③ Hemoptysis: seen in about 30% of cases, often progressing to pulmonary infarction. ④ Cough: manifests as a sudden, irritating cough, seen in about 50% of patients. ⑤ Panic or a sense of frequent death: seen in 50% to 60% of patients. ⑥ Syncope: mainly seen in patients with larger PE, due to a sharp decrease in cardiac blood output and a sharp drop in blood pressure leading to cerebral ischemia. (7) Other: chest tightness, palpitation, shortness of breath and dizziness are also common symptoms.
Major signs ① Accelerated respiration: Most patients have increased respiration. It is suggested that PE can be excluded if the respiratory rate is <16 times/min. ②Increased heart rate: more than half of the patients have a heart rate of >100 times/min. ③Cyanosis: about 20% of the cases are accompanied by cyanosis. ④ Peripheral circulatory failure: caused by decreased blood pressure or shock and poor tissue perfusion. ⑤ Acute pulmonary hypertension and right heart insufficiency manifestations: hyperactive 2nd heart sound in the pulmonary valve auscultation area, systolic jet murmur can be heard in the 2nd intercostal space at the left edge of the sternum, and a significant systolic beat can be seen, occasionally a diastolic murmur can be heard, which is caused by pulmonary valve closure insufficiency, and some patients can have atrial gallop rhythm, jugular vein anger and filling. (6) Hepatomegaly and lower limb edema: about 20% of patients have these signs, suggesting the development of right heart failure. (7) Wet rales can be heard in the affected lung in more than half of the patients, and sometimes pleural and pericardial rubs can be heard.
Diagnosis
The diagnosis is made on the basis of clinical manifestations, laboratory tests and various auxiliary examinations.
1, clinical manifestations: may be manifested as ① sudden dyspnea (or sudden aggravation of existing dyspnea), choking cough, hemoptysis, chest pain, etc. ② Unexplained acute right heart failure and shock. ③ Systolic murmur in the pulmonary valve area with increased intensity and hyperactive 2nd heart sound in the pulmonary valve area. If there is evidence of peripheral venous thrombosis, the diagnosis of PE is further supported. Combined with blood gas analysis, electrocardiogram, chest X-ray and pulmonary ventilation and perfusion scan, the diagnosis can basically be made, and if necessary, pulmonary arteriography to confirm the diagnosis.
2, laboratory tests ① D-dimer is a specific degradation product produced by fibrin monomer cross-linked by activation factor XII and then hydrolyzed by fibrinolytic enzymes. d-dimer mainly reflects fibrinolytic function. Increased or positive results are seen in secondary fibrinolytic hyperfunction, such as hypercoagulable states, diffuse intravascular coagulation, renal disease, organ transplant rejection, and thrombolytic therapy. Although this test is highly sensitive, it is not specific enough to be used to confirm the diagnosis. However, patients with abnormally elevated D-dimer should be given special attention, while a D-dimer <500ug/L can largely exclude the diagnosis.
Arterial blood gas analysis Patients almost always have varying degrees of hypoxemia, with arterial partial pressure of oxygen (PaO2) < 80-85 mmHg, averaging 62-72 mmHg, and some believe that PaO2 > 90 mmHg can exclude PE. partial pressure of carbon dioxide (PaCO2) is mostly significantly decreased, showing hypocapnia, suggesting respiratory alkalosis, which is caused by hyperventilation.
(iii) Auxiliary tests
Pulmonary ventilation perfusion scan is currently the preferred method for the diagnosis of PE, and is an accurate non-invasive technique to accurately diagnose PE. The method is to have the patient inhale 133Xe radioactive gas or 99mTc-labeled drug by nebulized inhalation to show ventilation. Pulmonary angiography (PA) is the most reliable method for the diagnosis of PE, showing vascular lesions up to 0.5 mm in diameter and the location, extent, and degree of lesions and pulmonary function. The diagnosis is confirmed if there are signs of intrapulmonary filling defects, complete blockage of pulmonary artery branches, absence of perfusion in the lung fields or delayed filling and emptying of pulmonary artery branches. Pulmonary angiography has certain risks, especially in patients with pulmonary hypertension, with a disability rate of 1 % and a mortality rate of 0. 01 % to 0. 5 %, and is currently used only for differential diagnosis of complex cases and to obtain hemodynamic information. (iii) Radionuclide lung ventilation-perfusion scan is now used as the most common test for the diagnosis of PE. However, some underlying diseases such as chronic obstructive pulmonary disease, congestive heart failure, bronchiectasis, pneumonia, interstitial lung disease and lung cancer can affect the pulmonary ventilation and blood flow status of patients, which makes the determination of ventilation-perfusion scan very complicated and needs to be combined with clinical evaluation. ④ Spiral CT angiography can replace the ventilation-perfusion scan as the initial examination method. This method can directly show emboli and is highly accurate. ⑤ MRI has the advantage of being able to image in both the coronal and sagittal planes. Plain MRI can only show emboli in larger vessels, but not in the peripheral pulmonary arteries.
Treatment
General treatment: This disease has an acute onset and requires emergency treatment.
1, the patient should be kept absolutely bed rest, high concentration of oxygen. Place a central venous pressure catheter, measure the central venous pressure, control the infusion volume and speed, and administer drugs through this route. Analgesia: When there is severe chest pain, morphine 5-10mg can be used, injected subcutaneously, and avoided for those in shock.
2.Anti-shock: To reduce vagal excitability and prevent pulmonary vascular and coronary artery reflex spasm, intravenous injection of atropine 0.5~1mg, also available isopropyl adrenaline, phentolamine (benzamazoline). Anti-shock commonly used dobutamine 200mg added to 500ml glucose solution intravenous, the starting rate of 2.5μg/(kg?min), later adjust the drip rate to maintain systolic blood pressure at 12.0kPa (90mmHg) [in 10-25μg/(kg?min)].
3.Treatment of heart failure Toxicoside K 0.25 mg or Trichoside C 0.2~0.4 mg added to 50 % glucose solution 40 ml intravenously, repeat the dose in 4~6 hours if necessary.
4.Treatment of bronchospasm Administer aminophylline 0.25 g to 50% glucose solution 40 ml intravenously, and if necessary, dexamethasone 10 mg intravenously.
5.Control arrhythmia Fast ventricular arrhythmia, lidocaine 50-100 mg intravenously, followed by 1-2 mg/min intravenous drip. For rapid atrial arrhythmias, trichostatin C 0.2-0.4 mg in 50% glucose solution 20-40 ml intravenously or verapamil (isobodine) 5 mg in 50% glucose solution 20-40 ml intravenously is preferred.
Second, anticoagulation therapy Once the diagnosis is clear or highly suspected PE, anticoagulation therapy should be started immediately to prevent the continued development and recurrence of embolism.
1, currently commonly used are common heparin (UFH), low molecular heparin (LWMH) and warfarin. Heparin is a negatively charged protein that does not pass through the placenta. It is commonly used as a continuous intravenous infusion with a loading dose of 2000-3000 U/h, followed by 750-1000 U/h or 15-20 U/(kg. h) maintenance, and the dose is adjusted according to the activated partial thromboplastin time, and the APTT is maintained at 1.5-2 times the normal value. The first dose may be used first in highly suspected cases. Low molecular heparin (LMWH) can be injected subcutaneously without laboratory monitoring because of its long half-life. Low-molecular heparin (5000U, qd), or tachyphyllin 0.2~0.4ml, qd or Bid.
2, vitamin K antagonist: a commonly used oral anticoagulant, which can inhibit coagulation factors dependent on vitamin K. At present, the most commonly used is vinblastine coumarin (new anticoagulation) tablets, fast onset of action, 36 ~ 48h after oral peak, the first amount of 2 ~ 4mg, maintenance amount of 1 ~ 2mg / d. Also available double coumarin or double coumarin ethyl ester (new double coumarin), the first dose of 200mg, the next day 100mg orally, after 25 ~ 75mg daily maintenance. Warfarin is 15-20mg for the first dose, 5-10mg the next day, and 2.5-5mg per day for maintenance, with an INR of 1.8-2.5. Because it takes several days to work, it is necessary to overlap with heparin/low-molecular heparin for at least 4-5 days until the oral anticoagulant takes effect, and then heparin is discontinued. Generally oral anticoagulants need to be continued for 3 to 6 months.
Warfarin applied at 6-11 weeks of gestation can cause “idiopathic embryopathy”, including nasal bone hypoplasia, epiphyseal dysplasia, central nervous system abnormalities, fetal and neonatal hemorrhage, and malformations. The drug can cause neonatal hemorrhage at any time during pregnancy and is given only after delivery. It is recommended to continue using it throughout pregnancy in order to weigh the advantages and disadvantages for the mother and fetus in patients after wind heart valve replacement.
3. Fibrinolytic agents, i.e., thrombolytic therapy. Thrombolysis for PE is the main progress in recent years, which can dissolve the thrombus in the pulmonary artery, improve pulmonary tissue perfusion, reduce pulmonary circulation resistance and pulmonary artery pressure, and improve right heart function; dissolve the thrombus in the deep venous system, and also reduce the source of emboli, reduce PE recurrence, and improve quality of life and long-term prognosis. Generally, treatment with fibrinolytic agents within 5 days after embolization is more effective and more suitable for acute giant pulmonary embolism, which can be used with heparin at this time, or heparin can be used after the end of its course. Commonly used drugs are streptokinase (SK), urokinase (UK) and tissue-type alteplase (fibrinogen activator), etc.
(1) Urokinase loading dose of 4400U/kg, 10min sedation, followed by 2200U/(kg?h) continuous sedation for 12h; another 2h thrombolytic regimen can be considered: 20,000U/kg continuous sedation for 2h.
(2) Streptokinase loading dose of 250,000 U for 30 min, followed by 100,000 U/h for 24 h. Streptokinase is antigenic, so intramuscular injection of diphenhydramine or dexamethasone is required before administration to prevent allergic reactions.
(3) Alteplase (rt-PA): 50-100 mg for 2 h. Do not use heparin during thrombolysis with urokinase and streptokinase. There is no special requirement to stop using heparin when thrombolysis with alteplase (rt-PA). The disadvantage is that it is expensive and difficult to be commonly used at present.
After thrombolysis, prothrombin time (PT) or activated partial thromboplastin time (APTT) should be measured every 24 h. When its level is lower than 2 times the normal value, standard heparin therapy should be restarted. After thrombolysis, dynamic observation of clinical and related auxiliary tests should be paid attention to assess the efficacy of thrombolysis.
Absolute contraindications to thrombolytic therapy include active gastrointestinal bleeding, intracranial bleeding within 2 months, and post-operative cranial and spinal surgery. Relative contraindications include major surgery within 10 days, childbirth, recent severe gastrointestinal bleeding, liver and kidney failure, severe trauma, hypertension grade III and bleeding disorders.
4. Surgical treatment
(1) Pulmonary embolectomy: The mortality rate is reported to be as high as 65%-70%. However, this operation can still save the lives of some patients, and the indications for the operation must be strictly controlled: (1) pulmonary arteriogram proves that 50% or more of the pulmonary vessels are obstructed, and the embolus is located at the main pulmonary artery or left or right pulmonary artery; (2) anticoagulation and/or thrombolytic therapy fails or is contraindicated; (3) after treatment, the patient is still in severe hypoxemia, shock, kidney and brain injury.
(2) Vena cava block: mainly to prevent the recurrence of embolism to the point of endangering the pulmonary vascular bed. Methods include surgical clips, umbrella devices, mesh sieve method, folding, etc. After vena cava block, the diameter of the vessels in the collateral circulation may increase, and the embolus may enter the pulmonary artery through the collateral circulation, and there may be thrombosis in the local area of the blocking device, so anticoagulation therapy must be continued after the operation.
5.Inferior vena cava filter Repeated PE is closely related to DVT of lower limbs and contraindicated for anticoagulation. In conclusion, PE should be highly suspected in patients with “unexplained dyspnea or concurrent hypotensive shock” in the perioperative period, and vasoactive drugs epinephrine, dopamine, dobutamine or endotracheal intubation should be applied in time to prevent sudden death. The death rate of untreated patients is as high as 25-30%, but reasonable treatment can reduce the death rate to 2%-8%. Therefore, the situation of PE prevention and treatment is very serious, and strengthening the awareness of PE prevention and improving the diagnosis level of PE are the keys to reduce the morbidity and mortality rate and improve the prognosis.
Prevention】
1.Generally, through careful clinical examination and early detection of deep vein thrombosis in lower limbs, PE can be prevented in 80% of patients. The following measures can be taken to prevent venous thrombosis.
① Caesarean section or difficult delivery should be operated gently and meticulously to reduce tissue damage, especially to avoid damage to blood vessels and induce thrombosis. During delivery, dehydration should be corrected in time to maintain water and electrolyte balance and prevent blood coagulation from increasing
②After delivery and surgery, encourage patients to turn and flex and stretch their lower limbs as much as possible, and instruct them to get out of bed early to reduce braking, promote blood return and enhance blood circulation.
③High-risk patients need auxiliary mechanical preventive measures such as: elastic stockings, gradient pressure pumps, etc., and apply prophylactic anticoagulation therapy when necessary.
2.Drug anticoagulation to prevent thrombosis
①Small dose heparin to prevent the occurrence of postoperative DVT and PE has a positive effect, especially for those who are over 40 years old, obese, malignant tumor and varicose veins. Before performing pelvic and hip surgery, measure partial thromboplastin time (APTT) and platelets, D-D, if normal, inject heparin 5000U subcutaneously 2h before surgery, and administer the drug again 12 hours after surgery until the patient can get up and move around, usually 5 ～The patient can get up and move around, usually 5 to 7 days. Because of the low dose of heparin, it is not easy to complicate complications such as heparin-visited thrombocytopenia, and monitoring of coagulation mechanism is not required.
② oral anticoagulants: such as acenocoumarol (new anticoagulant tablets) (acenocoumarol, sinfrom), warfarin (benzylacetone coumarin, warfarin) is commonly used in people with a history of DVT, severe varicose veins, as prophylactic anticoagulation therapy.
③ Anti-platelet agents: dipyridamole tablets, 100 mg per day orally, small doses of aspirin (0,3 to 1,0 g per day orally), can inhibit platelet aggregation and adhesion. Non-steroidal anti-inflammatory agents such as perindomethacin can inhibit thrombin A2 and reduce venous thrombosis.