Pulmonary embolism

Essentials

• Pulmonary embolism (PE) is a disturbance of the pulmonary circulation often with nonspecific signs and symptoms. It is very common (at population level 0.5–1 cases per 1 000 annually). If not diagnosed and treated promptly PE may prove to be fatal.
• The pretest probability of PE must be included in the differential diagnosis of all patients who present with chest pain and dyspnoea, particularly in those with coexisting risk factors.
• PE most commonly originates from lower limb deep vein thrombosis (DVT).
  • DVT may be clinically asymptomatic.

Classification

• PE can be classified into three grades (see table ) according to the associated risk of early death.
  • PE associated with a high risk of death causes haemodynamic instability, and the patient is in shock or has hypotension.
  • A moderate risk of death is associated with a condition where there is no haemodynamic instability but the PE causes right heart strain. Right ventricular strain can be identified with imaging studies (echocardiography, CT), ECG or by an increased concentration of troponin or NT-proBNP. Myocardial damage causes an increased troponin (or another cardiac marker) concentration (moderate risk, even in the absence of right ventricular strain).
• Additionally, clinical evaluation of the risk of death is recommended, e.g. based on the PESI or sPESI risk classifications (table ).

Risk factors

• PE is rare in patients with no coexisting risk factors.
• For the most common risk factors, see .

Signs and symptoms

• Dependent on the size and location of the embolus The most common symptoms are dyspnoea chest pain cough, haemoptysis collapse.
• Tachypnoea and tachycardia correlate with the severity degree of PE. tachypnoea hypotension, syncope tachycardia narrow pulse pressure cyanosis increased venous pressure.
• Pulmonary infarction is rare, but is suggested by
  • pleuritic pain
  • friction rub
  • focal parenchymal infiltrates in a chest x-ray.

Clinical assessment

Assessment of pretest probability

• A clinical assessment of the pretest probability plays a central role in diagnosis and must be carried out before planning or interpreting any investigations (see table ).

Investigation and treatment strategy in suspected PE

• If the probability of PE is at least moderate, heparin therapy is started before imaging studies. If the patient looks unwell or is hypoxic, emergency treatment must be commenced and the patient transferred without delay to a hospital where the diagnosis can be confirmed.
• The pretest probability of pulmonary embolism should always be assessed (table ).
  • If the pretest probability is high, CT angiography of the pulmonary arteries or ultrasonography of the legs is indicated.
  • Particularly if CT is contraindicated due to the contrast medium or the radiation burden, the first-line investigation is ultrasonography of the lower extremities.
  • As an alternative, a perfusion scan can be performed. If ultrasonography shows DVT, treatment is started. If ultrasonography is negative, follow-up investigations (CT angiography or a nuclear scan of the lung) are indicated to confirm diagnosis. "?>
  • If the pretest probability is low or moderate, the D-dimer test is indicated.
    • If the D-dimer test is negative, PE has been excluded and no further investigations are needed.
    • If the D-dimer test is positive, the investigations are continued as for high pretest probability (see above).

Diagnosing PE

CT angiography of the pulmonary arteries

• The most important test for PE
• Detects emboli up to the level of the subsegmental arteries and will also demonstrate right ventricular strain.
  • A normal finding is usually sufficient to exclude PE.
• Requires a contrast medium.
• Plasma creatinine must be checked.

Perfusion scan (nuclear scan)

• A perfusion scan should be carried out if the CT scan is contraindicated.
• A circulatory disturbance caused by an embolus will show up as a perfusion defect.
• The result is significant only if it is
  • clearly positive or
  • clearly negative.
• Interpretation is hindered by
  • asthma
  • COPD
  • parenchymal diseases.
• Simultaneous ventilation scanning is usually necessary, i.e. a V/Q scan (except, for example, in young pregnant women in whom the ventilation scanning would unnecessarily increase the radiation exposure).

Ultrasonography of the legs

• The investigation is indicated if there are signs of lower limb DVT.
• Local availability and resources determine the order of investigations.
• If ultrasonography is used as the first-line imaging study, pulmonary embolism can be diagnosed merely by the presence of typical clinical presentation and positive ultrasonography findings.

Laboratory tests

Arterial blood gas analysis

• Low partial pressure of oxygen in arterial blood (PaO₂ less than 9 kPa) is a common finding. Low oxygen saturation levels measured by pulse oximetry may be suggestive of PE.
• Low partial pressure of carbon dioxide (PaCO₂ less than 4.5 kPa) is caused by hyperventilation.
• A normal blood gas analysis does not exclude the possibility of PE.

D-dimer

• Activation of the clotting system triggers the body’s own fibrinolysis, which is manifested by an increased concentration of D-dimer.
• The finding is not diagnostic of PE, but a normal plasma D-dimer concentration does nevertheless exclude PE in a patient with low or moderate pretest probability.

Other laboratory tests

• Acute stretching of the right ventricle may lead to myocardial damage and increased concentrations of cardiac markers (TnT, TnI, BNP, NT-proBNP).
• Thrombophilia screening, indications; see Deep vein thrombosis .

Chest x-ray

• A plain chest x-ray is usually normal, but a wedge-shaped consolidation can be present in pulmonary infarction. Dilatation of the pulmonary artery trunk is indicative of pulmonary hypertension. A lung field with diminished vascular markings (empty) on the affected side is sometimes seen in massive PE.

ECG

• ECG changes
  • are dependent on the degree of right heart strain, i.e. the size of the embolus.
  • are dynamic in nature.
• The most common ECG changes are:
  • sinus tachycardia
  • T wave inversion in chest leads (V1–V3)
  • partial RBBB or S1Q3 pattern)

Echocardiography

• Will demonstrate right heart strain.
• Echocardiography is very quick to execute and should therefore be considered as the first-line investigation when there is a suspicion of high-risk PE.
• Indicated if thrombolytic therapy is considered and moderate-risk PE is suspected.

Treatment

Treatment of circulatory shock

• Cautious i.v. fluid therapy
• If necessary, drugs to raise blood pressure
  • Noradrenaline, dopamine
• Adequate oxygenation, FiO₂ initially 100% if necessary.
• Opioids should be administered, if needed, to sedate the patient.
  • Morphine 4–6 mg i.v.
• Thrombolytic therapy or mechanical removal of the embolus.

Deciding on the treatment

• A PE with high risk of death, leading to haemodynamic collapse and hypotension is treated with thrombolysis whereas PE with few symptoms may be managed with anticoagulants.
• Echocardiography is used to aid decisions regarding the treatment of PE between the two above extremes.
• If echocardiography shows signs of right heart strain (submassive PE), thrombolysis may be considered should the patient's clinical condition worsen during the antiocoagulant therapy.
• Small PE does not cause haemodynamic imbalance.
• PE older than 2 weeks does not warrant thrombolysis.
• If the clinical picture is dominated by a massive lower limb DVT, it must be treated as a priority .
• The usual contraindications to thrombolysis apply.

Anticoagulant therapy

• See article Deep vein thrombosis Treatment is carried out with low molecular weight heparin (LMWH) and warfarin or rivaroxaban; see below. Dalteparin 100 IU/kg twice daily s.c. Enoxaparin 1 mg/kg twice daily s.c.Tinzaparine 175 IU/kg once daily s.c.The effect of tinzaparine can be reversed with protamine more completely than when using the other drugs mentioned above.May also be used in patients with renal failure (if eGFR > 20–30 ml/min; calculator ). Fondaparinux by subcutaneous injection 7.5 mg once daily, if heparin is not suitable. Warfarin is started concomitantly, either 5–10 mg/day or with the estimated maintenance dose for 2 days and then as guided by INR readings (does not apply for patients with cancer who are treated with LMWH for 3–6 months). Heparin is continued until INR has ben within the target range (2.0–3.0) for 48 hours in any case for at least 5 days. Patients with active cancer are treated with LMWH for the first 3–6 months. LMWH is safe for the treatment of pregnant women. If necessary, thrombolytic therapy may be carried out also during pregnancy.Rivaroxaban is a new alternative to warfarin. Its dosage does not require laboratory monitoring.The drug is started without preceding heparin at a dose of 15 mg twice daily which is continued for 3 weeks.In further treatment the dose is 20 mg once daily provided that eGFR is at least 15 ml/min.

Thrombolytic therapy (fibrinolytic therapy)

• Tenecteplase
• Alteplase in a routine 100 mg dose and reteplase are possible alternatives.
  • Reteplase and tenecteplase are possible alternatives.
  • LMWH is started simultaneously with thrombolytic therapy.
• Warfarin is not started until thrombolytic therapy is completed.

Inferior vena cava filter (IVC filter)

• If the patient has a particularly high risk of DVT or PE and anticoagulant therapy is contraindicated, a temporary IVC filter can be recommended until the contraindication is no more effective.
• The insertion of a temporary IVC filter should be considered for the duration of surgical procedures in situations where the risk of PE is significantly increased and anticoagulation is contraindicated. A temporary IVC filter warrants hospitalisation and immobilisation, and the benefits must be carefully weighed against the risks.
• The filter must be removed as soon possible, and no later than after 2 weeks.

Invasive or surgical management

• If thrombolysis fails to improve the patient’s clinical condition, percutaneous mechanical breaking up of the emboli, local thrombolytic therapy or surgical embolectomy may be considered on a case by case basis.

Follow-up management

• See Deep vein thrombosis; treatment .
A follow-up visit after 3–6 months should be arranged for patients whose pulmonary artery pressure was initially significantly elevated, and an echocardiography should be carried out for, in particular, symptomatic patients (NYHA 2 or more).
• The need for echocardiography can be screened with the help of natriuretic peptides; a low concentration excludes a significant right heart strain.
Permanently elevated pulmonary artery pressure requires more detailed investigations for chronic thromboembolic pulmonary hypertension .See Deep vein thrombosis; treatment .If echocardiography has shown the pulmonary artery pressure to be significantly elevated, the investigation is recommended to be repeated after 3–6 months.Permanently elevated pulmonary artery pressure requires more detailed investigations for chronic thromboembolic pulmonary hypertension . If resources for performing echocardiography are limited, plasma NT-proBNP concentration can be used as a screening test after 3–6 months.If the concentration is low (in practice less than 450 ng/l), echocardiography would probably not bring any additional benefit.

Related resources

• Cochrane reviews
• Other evidence summaries
• Clinical guidelines
• Literature