Guidelines for the diagnosis and treatment of acute pulmonary embolism
Basic Concept
u Pulmonary embolism (PE) is a clinical and pathophysiological syndrome in which endogenous or exogenous emboli obstruct the pulmonary artery causing pulmonary circulation obstruction, including pulmonary thromboembolism, fat embolism syndrome, amniotic fluid embolism, air embolism, tumor embolism, etc. Qingqing Ma, Department of Respiratory Medicine, Shandong Provincial Chest Hospital
u Pulmonary infarction (PI): refers to the occurrence of pulmonary embolism causing bleeding or necrosis of lung tissue
u Venous thromboembolism (VTE): PTE and DVT are two different stages of the same disease process, collectively referred to as VTE.
Pulmonary thromboembolism (PTE): The disease is caused by obstruction of the pulmonary artery or its branches by thrombus from the venous system or the right heart, with pulmonary circulation and respiratory dysfunction as its main clinical and pathophysiological features.
Deep venous thrombosis (DVT): Clots (thrombi) are formed in the lumen of deep veins by fibrin, platelets, red blood cells and other blood components.
Predisposing factors for venous thromboembolism
Susceptibility factors Patient-related Environment-related Susceptibility factors Patient-related Environment-related
Strong susceptibility factor (OR > 10) Moderate susceptibility factor (OR 2-9)
Fracture (hip or leg) ü Arthroscopic knee surgery ü
Hip or knee replacement ü Central venous line placement ü
Major general surgery ü Chemotherapy ü
Major trauma ü Chronic heart failure or respiratory failure ü
Spinal cord injury ü Hormone replacement therapy ü
Weak predisposing factors (OR <2) Malignancy ü
Bedridden > 3 days ü Stroke episode ü
Sedentary lifestyle ü Oral contraceptive treatment ü
(e.g., long-distance car or air travel) ü Pregnancy/postpartum ü
Ageing ü Pre-existing lower limb venous thrombosis ü
laparoscopic surgery propensity to thrombosis ü
(e.g. cholecystectomy) ü
Obesity ü
Pregnancy/pre-partum ü
Varicose veins ü
Natural course of pulmonary embolism
PE occurs 3-7 days after deep vein thrombosis; 10% of patients die within 1 hour of the onset of PE symptoms. 5-10% of PE present with shock or hypotension; 50% of patients do not have shock but have laboratory evidence of right ventricular dysfunction or impairment; 90% of deaths are untreated, only 10% of deaths treated, 0.5-5% of treated PE patients develop chronic thromboembolic pulmonary hypertension, and 50% of patients with symptomatic PE or DVT who are not treated with anticoagulation have a recurrence within three months.
Clinical manifestations
Unexplained dyspnea, chest pain, hemoptysis, irritability, syncope, cough, palpitations
Signs: rapid breathing, tachycardia, DVT signs, fever, pallor
Key indicators of acute pulmonary embolism risk stratification
Clinical features Shock
Hypotensiona
Right ventricular insufficiency Echocardiography shows enlarged right heart
Decreased exercise or pressure overload manifestations
Spiral CT showing right heart enlargement
Elevated BNP or NT-proBNP
Increased right ventricular pressure on right heart catheterization
Markers of myocardial injury Positive cardiac troponin T or I
a: Definition of hypotension: systolic blood pressure <90 mmhg or blood pressure decrease >40 mmHg for more than 15 minutes, except for hypotension due to new arrhythmia, hypovolemia or sepsis.
Acute pulmonary embolism risk stratification
Risk of early death Risk stratification indicators Recommended treatment
Clinical presentation Right ventricular insufficiency Myocardial injury
(shock or hypotension)
High risk + a a Thrombolysis or embolectomy
(>15%)
Non Intermediate risk – + +
High (3%-15%) – + – Hospitalization
Critical – – +
Low risk
(<1%) - - - Early discharge or out-of-hospital treatment
Clinical likelihood scoring system (Wells score)
Variable Score
Predisposing factors
Pre-existing DVT or PE 1.5
Recent surgery or braking 1.5
Tumor 1
Symptoms
Hemoptysis 1
Physical signs
HR>100bpm 1.5
Clinical signs of DVT (lower extremity circumference measurement) 3
Diagnosis of other diseases less likely than PE 3
Clinical likelihood: low <2.0; moderate 2.0-6.0; high >6.0
Diagnostic methods for pulmonary embolism
1. D-dimer: sensitivity 95%, specificity 40%. Tumor, inflammation, infection, tissue necrosis and aortic coarctation can cause elevated D-dimer, so the positive predictive value is not high. In patients with a low to moderate clinical likelihood of PE, a negative D-dimer (<500 ng/L) can exclude the diagnosis without further imaging. In patients with a high clinical likelihood of PE, a normal D-dimer does not exclude the diagnosis of pulmonary embolism.
2, venous compression ultrasound (CUS): 90% sensitivity and 95% specificity for the diagnosis of DVT. Patients with suspected PE who have negative monolayer spiral CT or allergic to contrast or renal insufficiency are recommended to undergo lower extremity CUS to further exclude the diagnosis of diagnostic pulmonary embolism.
3.Pulmonary ventilation/perfusion nuclide scan (V/Q scan): has important diagnostic significance for PE diagnosis or exclusion diagnosis, its specificity is high, and PE can be basically excluded when the test result is normal or close to normal; the possibility of PE is also high when V/Q scan is highly probable, but further examination should be performed to clarify the diagnosis.
4.CT scan/(SDCT and MDCT): can make the diagnosis of pulmonary embolism above the segment
Single layer spiral CT (SDCT): the specificity is 90%, but the sensitivity is only 70%, therefore, if SDCT is negative, the diagnosis must be excluded by lower limb venous pressure ultrasound
Multilayer spiral CT (MDCT): 96% specificity and 90% sensitivity, can be used as the first-line confirmatory diagnosis of PE, direct sign: low-density filling defect in the pulmonary artery. Indirect: wedge-shaped banding in the lung field, disciform pulmonary atelectasis.
5.Pulmonary arteriography: It is the “gold standard” for the diagnosis of PE, but it is invasive and prone to fatal complications, so it is rarely used now and has been replaced by CTPA.
6.Cardiac ultrasound: It has little diagnostic significance for suspected non-high-risk PE, with a sensitivity of only 60-70%, and negative results cannot exclude PE; however, it can detect the presence of right ventricular dysfunction and facilitate risk stratification, and can also exclude some cardiovascular diseases.
For patients with high-risk PE with shock or hypotension, ultrasound can show indirect signs of pulmonary hypertension or right ventricular overload, and if other tests cannot be performed, the diagnosis of PE can be made based on ultrasound
Diagnostic strategy 1 Diagnostic process for patients with suspected high-risk acute pulmonary embolism
Patients with suspected high-risk acute pulmonary embolism (with hypotension or shock)
Availability of immediate pulmonary artery-enhanced MDCT
No Yes
Echocardiography
Right heart load Enhanced CT
Not increased Increased Positive Negative
Availability of enhanced CT examination
Stable condition
Treat as pulmonary embolism Look for other causes
Look for other causes Lack of other tests Consider thrombolysis or thrombectomy
or unstable disease
Diagnostic Strategy 2 Diagnostic Process for Suspected Non-High-Risk Acute Pulmonary Embolism
Patients with suspected non-high-risk acute pulmonary embolism (without hypotension or shock)
Assessment of clinical likelihood of pulmonary embolism (based on clinical experience or scoring rules)
Low or moderate probability High probability
D-dimer Enhanced MDCT
Negative Positive No pulmonary embolism With pulmonary embolism
No treatment Enhanced MDCT No treatment Treatment
or further search for other causes
No pulmonary embolism With pulmonary embolism
No treatment Treatment
Specific recommendations for diagnostic measures
Based on risk stratification and clinical likelihood, appropriate diagnostic methods are selected and diagnosis is made for different test results.
Suspected high-risk PE: emergency CT or bedside cardiac ultrasound is recommended for diagnosis (1C)
Suspicious non-high-risk PE: Diagnostic strategy should be selected based on clinical likelihood (1A)
*Recommend emergency D-dimer investigation in the emergency department using highly sensitive methods; minimize imaging and radiography (1A)
* Consider performing lower extremity venous compression ultrasound to look for DVT; if the result is positive, further imaging can be avoided (IIb-B)
* Cardiac ultrasound is not recommended for diagnosis (IIIC)
* Pulmonary CT imaging should be considered when there is a discrepancy between clinical evaluation and non-invasive imaging findings (IIa-C)
* Different diagnostic criteria depending on clinical likelihood (1B)
PE treatment
I. General treatment: intensive care, detect changes in respiration, heart rate, blood pressure, ECG and blood gas; prevent re-dislodgement of embolus, absolute bed rest, keep stool unobstructed, avoid exertion; use appropriate sedative drugs to relieve anxiety and panic symptoms; provide pain relief for chest pain.
Second, respiratory and circulatory support treatment
1.Respiratory support: administer oxygen via nasal cannula or face mask; for severe expiratory failure, non-invasive mechanical ventilation via face mask or mechanical ventilation via tracheal intubation (Note: positive end-breath pressure will reduce venous blood return and aggravate right heart failure); avoid tracheotomy to avoid local hemorrhage during thrombolysis or anticoagulation.
2. Circulatory support: right heart insufficiency, reduced cardiac output
*If blood pressure is normal, dobutamine and dobutamine (IIa-B) with certain pulmonary vasodilator effect and positive inotropic effect can be given.
*In those with decreased blood pressure, other vasopressors such as methotrexate or epinephrine (1C)
*Volume expansion therapy exacerbates right ventricular enlargement and decreases cardiac output and is not recommended; fluid loading should be controlled. (IIIB)
III. Thrombolytic therapy
Thrombolysis recommendations 2008
u Thrombolysis is the first-line therapy in patients with high-risk pulmonary embolism in cardiogenic shock and/or persistent hypotension, in the absence of absolute contraindications. (1A)
u Catheter fragmentation or surgical embolization may be used in high-risk patients with contraindications to thrombolysis. (IIb-C)
Intraductal thrombolysis is as effective as peripheral intravenous thrombolysis.
u Routine thrombolysis is not recommended for non-high-risk (intermediate-risk, low-risk) patients. (IIb-B)
Thrombolysis may be given in some intermediate-risk patients after a full weighing of the risk of bleeding benefit.
Thrombolytic therapy is not recommended for low-risk patients. (IIIB)
Time window for thrombolytic therapy: usually within 2 weeks of the onset or recurrence of acute pulmonary embolism, with the greatest benefit from thrombolysis within 48 hours of symptom onset, and the earlier thrombolysis is started, the better the outcome.
Thrombolytic drugs and thrombolytic regimen
1.Urokinase: 4400IU/Kg intravenous loading dose for 10 min, followed by 4400IU/Kg/h maintenance for 12-24 hours
Rapid administration: 3 million IU for 2 hours
Domestic expert consensus recommends the use of urokinase treatment in China: UK 20000 IU/kg/2h intravenous drip
2. rt-PA (Ritonel): 100mg for 2 hours or 0.6mg/Kg for 15 minutes (maximum dose 50mg)
Expert consensus recommended rt-PA usage: 50-100 mg continuous intravenous drip 2h dosing method for static push 10 mg, 90 mg intravenous injection 2 hours
Transcatheter intrapulmonary artery local injection of rtPA has not shown any advantage over intravenous thrombolysis. This mode of administration should therefore be avoided as it increases the risk of bleeding at the puncture site
Contraindications to thrombolytic therapy for acute pulmonary embolism
Absolute contraindications: (1) active internal bleeding; (2) recent spontaneous intracranial hemorrhage.
Relative contraindications: (1) major surgery, delivery, organ biopsy or vascular puncture that cannot be stopped by compression within 2 weeks (2) ischemic stroke within 2 months; (3) gastrointestinal bleeding within 10 days; (4) severe trauma within 15 days; (5) neurosurgical or ophthalmic surgery within 1 month; (6) severe hypertension (systolic >180 mm Hg, diastolic >110 mm Hg) that is difficult to control 110 mm Hg); (7) recent cardiopulmonary resuscitation; (8) platelet count less than 100 × 109/L; (9) pregnancy; (10) bacterial endocarditis; (11) severe hepatic or renal insufficiency; (12) diabetic hemorrhagic retinopathy; (13) bleeding disorders; (14) aneurysm; (15) left atrial thrombosis; (16) age >75 years.
IV. Anticoagulation therapy
u Initial anticoagulation therapy
Ø The purpose of initial anticoagulation therapy for acute pulmonary embolism is to reduce death and recurrent embolic events.
u Long-term anticoagulation therapy
The purpose of long-term anticoagulation in patients with acute pulmonary embolism is to prevent fatal and non-fatal venous thromboembolic events.
u Anticoagulation should be initiated in patients with suspected acute pulmonary embolism while awaiting further confirmation of the diagnosis. (1C)
u Sequential anticoagulation therapy after thrombolysis in high-risk patients. (1A)
u Anticoagulation is the basic therapeutic measure in intermediate- and low-risk patients. (1A)
Commonly used anticoagulant drugs
u Commonly used anticoagulants
u Non-oral anticoagulants: normal heparin, low molecular weight heparin, sulforaphane
u Oral anticoagulants: warfarin
Note: Aspirin and clobigrel are not recommended for the treatment of venous thrombosis.
General heparin anticoagulation therapy
Indications for the use of plain heparin
u Patients with renal insufficiency (because normal heparin is cleared by the reticuloendothelial system and is not metabolized by the kidneys)
u Patients with high bleeding risk (because the anticoagulant effect of normal heparin can be rapidly neutralized)
u In other patients with acute pulmonary embolism, low molecular weight heparin may be an alternative to plain heparin.
Normal heparin anticoagulation treatment methods
The common method of administration of plain heparin is by intravenous drip with an initial loading dose of 80 U/kg (typically 3000-5000 U) followed by 700-1 000 U/h or 18 U/kg/h maintenance. Treatment with normal heparin requires monitoring of the activated partial thromboplastin time (APTT), which should be at least 1.5 times greater than the control value (usually 1.5 times to 2.0 times).
Low molecular heparin anticoagulation therapy
Compared to regular heparin, sulforaphane has the same anticoagulant effect as low-molecular-weight heparin and does not require APTT monitoring.
Low-molecular-weight heparin and sodium fondaparinux dosing regimen
Drug Dose Interval
Enoxaparin 1.0 mg/kg every 12 h
(enoxaparin) or 1.5 mg/kg once daily
Tinzaparin 175 U/kg once a day
(Tinzaparin)
Fondaparinux 5 mg (weight 50 kg) once daily
(Fondaparinux) 7.5 mg (body weight 50C100 kg)
10 mg (body weight 100 kg)
Oral anticoagulant anticoagulation therapy
u The most commonly used oral drug is warfarin, which should be used initially overlapping with heparin until the INR is reached (2.0-3.0) for 2 days before discontinuing heparin.
The starting dose is usually 5 mg for young (<60 years old) or previously healthy out-of-hospital patients, while for elderly and hospitalized patients, the starting dose is usually 2.5-3 mg, with subsequent dose adjustment according to the International Normalized Ratio (INR), and the INR should be maintained between 2.0 and 3.0 for long-term users.
Duration of anticoagulation therapy
The duration of anticoagulation for acute pulmonary embolism should be individualized and generally takes at least 3 months.
u If acute pulmonary embolism (0.5-5% of patients) develops into chronic thromboembolic pulmonary hypertension, long-term anticoagulation should be used.
The duration of anticoagulation should be determined according to the type of thrombogenic trigger if the acute pulmonary embolism is successfully treated, symptoms largely resolve, there is no right heart pressure load, and the pulmonary embolism largely disappears on imaging.
u The recommended duration of anticoagulation for patients with pulmonary embolism caused by temporary or reversible precipitating factors (estrogen administration, temporary braking, trauma and surgery) is 3 months. (1A)
u Anticoagulation is recommended for at least 3 months in patients with first pulmonary embolism without obvious precipitating factors (idiopathic venous thrombosis), with the risk of bleeding and benefit assessed after 3 months before deciding on long-term anticoagulation, and for patients without risk of bleeding and for whom anticoagulation monitoring is convenient. (1A)
u Long-term anticoagulation is recommended for patients with reoccurring pulmonary embolism without predisposing factors. (1A)
u Long-term anticoagulation should be recommended for patients with long-standing risk factors for venous thromboembolism, such as cancer patients, anticardiolipid antibody syndrome, and prone to embolism. (1C)
Indications for inferior vena cava filter implantation
Pulmonary embolism combined with contraindication to anticoagulation or complications of anticoagulation therapy
Pulmonary embolism recurrence after adequate anticoagulation therapy
Prevention of high-risk patients: (1) extensive and progressive venous thrombosis; (2) catheter intervention or pulmonary artery thrombectomy; (3) severe pulmonary hypertension or pulmonary heart disease.
Since the filter can only prevent recurrence of pulmonary embolism and cannot treat DVT, anticoagulation is still required to prevent further thrombosis if there is no contraindication to anticoagulation after installation of the filter.
Acute pulmonary embolism diagnosis and treatment process
Suspicious patients
Signs, ECG, echocardiogram, D-dimer, blood gas analysis, cardiac enzymes
Anticoagulation if highly suspicious
Pulmonary artery enhancement CT or nuclear lung perfusion
Risk stratification (blood pressure, right heart load, cardiac enzymes)
High risk Moderate risk Low risk
Thrombolysis Anticoagulation Out-of-hospital anticoagulation