- Clinical science
Pulmonary embolism (PE) is the obstruction of one or more pulmonary arteries by solid, liquid, or gaseous masses. In most cases, the embolism is caused by blood thrombi, which arise from the deep vein system in the legs or pelvis (deep vein thrombosis) and embolize to the lungs via the inferior vena cava. Risk factors include immobility, inherited hypercoagulability disorders, pregnancy, and recent surgery. The clinical presentation is variable and, depending on the extent of vessel obstruction, can range from asymptomatic to cardiogenic shock. Symptoms are often nonspecific, including chest pain, coughing, dyspnea, and tachycardia. The diagnosis of PE is based primarily on the clinical findings and is confirmed by detection of an embolism in contrast CT pulmonary angiography (CTA). Arterial blood gas analysis typically shows evidence of respiratory alkalosis with low partial oxygen pressure, low partial carbon dioxide pressure, and elevated pH. Another commonly performed test is the measurement of D-dimer levels, which can rule out PE if negative. Empiric anticoagulation with heparin is initiated to prevent further thromboembolisms as well as to promote the gradual dissolution of the embolism and the underlying thrombosis. Blood-thinning therapy must be continued for at least three months with oral anticoagulants such as warfarin. In fulminant PE with shock, resolution of the thrombus with thrombolytic agents or removal in an emergency surgery is attempted.
- Accounts for ∼ 100,000 deaths in the US per year.
- Incidence rises with age.
- Sex: ♂ > ♀
Epidemiological data refers to the US, unless otherwise specified.
- (most common cause)
- Fat embolism during major surgical interventions (e.g., endoprosthesis replacement, osteosynthesis)
- Others: air embolism, amniotic fluid embolism, tissue embolism, cement embolism, bacterial embolism, tumor embolism
- Mechanism: thrombus formation (see ) → deep vein thrombosis in the legs or pelvis (most commonly iliac vein) → embolization to pulmonary arteries via inferior vena cava → partial or complete obstruction of pulmonary arteries
Pathophysiologic response of the lung to arterial obstruction
- Infarction and inflammation of the lungs and pleura
Impaired gas exchange
- Mechanical vessel obstruction → ventilation-perfusion mismatch → arterial hypoxemia (↓ PaO2) and elevated A-a gradient (see “Diagnostics” below)
- Elevated pulmonary artery pressure (PAP) due to blockage → right ventricular pressure overload → forward failure with decreased cardiac output → hypotension and tachycardia
- Acute onset of symptoms, often triggered by a specific event (e.g., on rising in the morning, sudden physical strain/exercise)
- Dyspnea and tachypnea (> 50% of cases)
- Sudden chest pain (∼ 50% of cases), worse with inspiration
- Cough and hemoptysis
- Possibly decreased breath sounds, dullness on percussion, split-second heart sound audible in some cases
- Tachycardia (∼ 25% of cases), hypotension
- Jugular venous distension
- Low-grade fever
- Syncope and shock with circulatory collapse in massive PE (e.g., due to a saddle thrombus)
- Symptoms of : unilaterally painful leg swelling
Consider PE as a differential diagnosis in recurring or progressive dyspnea of uncertain etiology!
Initial management according to modified Wells criteria
Hemodynamically stable patients (systolic BP > 90 mmHg) with high probability of PE (Wells score > 4) → CTA for definitive diagnosis
- Unless strongly contraindicated (e.g., high risk of bleeding, recent surgery), start empiric anticoagulation before conducting a CTA
- If too unstable for CTA → perform bedside echocardiography obtain a presumptive diagnosis of PE (right ventricle enlargement/hypokinesis or visualization of clot) prior to empiric thrombolysis.
In patients with a low or medium probability of PE (Wells score ≤ 4) → measure D-dimer levels (+ ABG evaluation + CXR)
- If positive (D-dimers ≥ 500 ng/mL) → CTA → evidence/exclusion of PE
- If negative → PE unlikely → consider other causes of symptoms (see “Differential diagnosis” below)
- The Wells score is used as a diagnostic algorithm in stable patients for assessing the probability of PE. The 2-tier model (modified Wells criteria) is generally more accepted for use among management guidelines.
- Note that a different version is used for determining the probability of DVT (see ).
|Clinical symptoms of DVT||3|
|PE more likely than other diagnoses||3|
|Tachycardia (heart rate > 100/min)||1.5|
|Surgery or immobilization in the past four weeks||1.5|
|Malignancy (being treated, in palliative care or diagnosis less than 6 months ago)||1|
|Wells criteria (clinical probability)|
Modified/simplified Wells criteria (clinical probability)
Initial test: measure D-dimer levels (if suspicion for PE low)
- D-dimers: fibrin degradation products detected in the blood after thrombus resolution via fibrinolysis; normal levels < 500 ng/mL
- If elevated in patients with low clinical probability of PE → further testing (see below)
- High sensitivity and negative predictive value: a negative D-dimer test most likely rules out PE
- Low specificity: positive results in all forms of fibrinolysis
- ↑ troponin T and B-type natriuretic peptide (BNP): possible elevation from right ventricular pressure overload → poor prognosis
Arterial blood gas (ABG) test
- Respiratory alkalosis; : ↓ paO2 < 80 mmHg, ↓ paCO2, ↑ pH
- ↑ Alveolar-arterial (A-a) gradient : compares the oxygenation status of alveoli to arterial blood
- ↓ O2 saturation
Normal D-dimer values usually rule out PE or DVT in patients with an unremarkable history and examination for PE! A positive D-dimer is unspecific since it may be elevated anytime elevated fibrinolysis is occurring.
Helical spiral CT/CT pulmonary angiography (CTPA): best definitive diagnostic test
- Contrast-enhanced imaging of the pulmonary arteries
- High sensitivity, specificity and immediate evidence of pulmonary arterial obstruction
- Visible intraluminal filling defects of pulmonary arteries
- Wedge-shaped infarction with pleural effusion is almost pathognomonic for PE
- Initially often performed to rule out other causes (e.g., pneumonia, pneumothorax, pericarditis, aortic dissection)
- Findings that may indicate PE
- Atelectasis (visible collapse or incomplete expansion of the lung)
- Pleural effusions
- Signs of pulmonary embolus (rare)
- Hampton's hump: wedge-shaped opacity in the peripheral lung with its base at the thoracic wall; caused by pulmonary infarction and not specific for PE
- Westermark sign: embolus leads to diminished perfusion of downstream lung tissue, which appears hyperlucent on radiograph.
- Fleischner sign: prominent pulmonary artery caused by vessel distension due to a large pulmonary embolus (common in massive PE)
- Echocardiography: to detect right atrium pressure (RAP) signs
- Indication: alternative to CT angiography in patients with severe renal insufficiency or contrast allergy
- Method: detects areas of ventilation/perfusion (V/Q) mismatch via perfusion and ventilation scintigraphy
- Perfusion failure in normally ventilated affected pulmonary area (mismatch) suggests PE
- Evidence of normal lung perfusion rules out PE → ventilation scintigraphy superfluous
- Indications: only conducted if CT angiography unavailable
- Procedure: right heart catheterization → insertion of a catheter into a pulmonary artery → radiograph after administration of contrast agent
Other diagnostic measures
- Electrocardiography (ECG)
- Compression Doppler ultrasound: diagnosis of potential underlying
Diagnostics for underlying cause
- Thrombophilia workup
- 45° reclining sitting posture
- Oxygen supplementation and intubation if respiratory failure
- IV fluids; and/or vasopressors in patients with hypotension
- Analgesics and sedatives
Non-life-threatening pulmonary embolism: therapeutic anticoagulation
- Empiric anticoagulation in patients with no absolute contraindication until definitive diagnosis has been made
An absolute contraindication for empiric anticoagulation is a high risk of bleeding (e.g., recent surgery, hemorrhagic stroke, active bleeding)!
- Initial anticoagulation (0–10 days)
Long-term anticoagulation and prophylaxis (3–6 months)
- Anticoagulation treatment is indicated for a minimum of three months after PE (see “Therapy” in ). The following agents may be used:
- Patients with a hypercoagulable state with DVT or PE: heparin followed by 3–6 months of warfarin for the first event, 6–12 months for the second, and lifelong anticoagulation for further events
Massive, life-threatening pulmonary embolism: recanalization
- Procedure: fibrinolysis, preferably with recombinant tissue-type plasminogen activator (tPA), e.g., alteplase
- Risk of hemorrhage during thrombolytic treatment
- Observe contraindications for thrombolytic therapy
- Treatment of last resort when thrombolysis is contraindicated or unsuccessful
- Surgical or catheter-based thrombus removal
There is no contraindication for systemic thrombolysis if the patient requires resuscitation!
- Inferior vena cava filter
- DVT prophylaxis: (subcutaneous heparin or LMWH for all immobile patients, early ambulation, and compression stockings)
- High risk of recurrence: without anticoagulant treatment ∼ 10% in the first year, ∼ 5% per year after
- Right ventricular failure
- Sudden cardiac death due to pulseless electrical activity
- Atelectasis (∼ 20% of cases)
- Pulmonary effusion
- Pulmonary infarction (∼ 10% of cases)
- Pneumonia from pulmonary infarction: peripheral infiltration on chest X-ray (typically wedge-shaped = )
We list the most important complications. The selection is not exhaustive.