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Veli-PekkaHarjola

Pulmonary Embolism

Essentials

  • Pulmonary embolism (PE) is a disturbance of the pulmonary circulation often with nonspecific signs and symptoms. If not diagnosed and treated promptly PE may prove to be fatal.
  • It is very common (0.5-1 cases per 1 000 annually).
  • The pretest probability of PE must be included in the differential diagnosis of all patients who present with chest pain or dyspnoea.
  • PE most commonly originates from lower limb deep vein thrombosis (DVT) which may be clinically asymptomatic.
  • Haemodynamically unstable patients are at high risk: send them to hospital immediately - by ambulance!
  • If the risk of death associated with PE is assessed as minor and the patient is feeling well, treatment can be started on an outpatient basis. However, hospital treatment is indicated even in such cases, if the patient has concomitant disease(s) complicating treatment.

Classification

  • PE can be classified into three grades according to the associated risk of early death.
    • PE is associated with a high risk of death if there is haemodynamic instability and the patient is in shock, has hypotension or develops cardiac arrest.
    • If there is no haemodynamic instability, the risk of death should be assessed based on clinical signs and concomitant diseases, using the sPESI risk classification, for example (Table T1). Based on this, patients can be divided into classes with moderate (sPESI HASH(0x2fd7118) 1) or low risk of death.
    • Right ventricular strain can be measured in specialized care (CT or echocardiography, troponins, NT-proBNP/BNP). These investigations can be used to assess the risk and required treatment setting and treatment in more detail.

Evaluating the risk of death in patients with PE based on the sPESI score1 . Source: Finnish Current Care Guideline on deep vein thrombosis and pulmonary embolism 2023 1.

CriterionsPESI
1 Source: Jiménez D, Aujesky D, Moores L et al. Simplification of the pulmonary embolism severity index for prognostication in patients with acute symptomatic pulmonary embolism. Arch Intern Med 2010;170(15):1383-9 [PubMed].
Age > 80 years1
Malignancy1
Heart failure
or
lung disease		1
Heart rate HASH(0x2fd7118) 110/min1
Systolic blood pressure < 100 mmHg1
Oxygen saturation < 90% with indoor air1
Interpretation
sPESI score30-day risk of death
0 points1.1%
1 point or more8.9%

Predisposing factors

  • PE is rare in patients with no predisposing factors.
  • For the most common predisposing factors, see Deep Vein Thrombosis.

Symptoms and findings

  • Depend on the size and location of the embolus and the capacity for circulatory compensation.
  • The most common symptoms are
    • dyspnoea (use a pulse oximeter to check oxygen saturation, but a normal level will not exclude PE)
    • chest pain
    • decreased physical performance
    • cough, haemoptysis
    • collapse.
  • Tachypnoea and tachycardia correlate with the severity of PE.
  • In severe PE, hypotension, shock and cardiac arrest
  • In rare cases, the body temperature and, in case of a large embolus, CRP levels may be elevated, which may misdirect the diagnosis towards an infection.
    • CRP levels may be elevated but low levels will not exclude PE.
    • If CRP levels are elevated, the possibility of infection or other inflammatory process must be assessed.

Clinical assessment

Assessment of pretest probability

Assessment of the clinical pretest probability of pulmonary embolism1 . Source: Finnish Current Care Guideline on deep vein thrombosis and pulmonary embolism 2023 1.

VariableScore
1 Source: Wells PS, Anderson DR, Rodger M, et al. Derivation of a simple clinical model to categorize patients' probability of pulmonary embolism: increasing the models utility with the SimpliRED D-dimer. Thromb Haemost 2000;83:416-420 [PubMed]
Symptoms of DVT and related findings3.0
Other diagnoses less likely than PE3.0
Heart rate >100 per min1.5
Immobilisation or surgery in the last 4 weeks1.5
Previous DVT or PE1.5
Haemoptysis1.0
Cancer (treatment ongoing, within previous 6 months or palliative)1.0
Clinical probability of PESum
Low (approx. 2%))<2.0
Moderate (approx. 20%)2.0-6.0
High (approx. 50%)>6.0

Investigation and treatment strategy in suspected PE D-Dimer Testing and Pulmonary Embolism

  • See figure 1.
  • Assess the pretest probability of PE T2.
    • If the pretest probability is high, CT angiography of the pulmonary arteries should be performed directly or, in special cases, ultrasonography or nuclear imaging of the lower extremity veins.
  • If the pretest probability is low or moderate, the D-dimer test is indicated. If the D-dimer level is higher than the cut-off level defined by the pretest probability, LMWH should be started before imaging.

Diagnosing PE Safety of Ruling out Acute Pulmonary Embolism in Outpatients by Normal Computed Tomography Pulmonary Angiography

Laboratory tests

D-dimer

  • Activation of the clotting system triggers endogenous 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. In such a case, no further investigations are necessary (see figure 1).
  • The D-dimer cut-off values depend on the pretest probability of PE. A concentration below the cut-off value excludes PE.
    • If the pretest probability is low, the cut-off value is 1.0 mg/l.
    • If the pretest probability is moderate, the cut-off values are:
      • 0.5 mg/l for people below 50 years of age
      • (age/100) mg/l for people of 50 or more years (e.g. 0.6 mg/l for people of 60 years).
  • If the D-dimer test is positive (value at the cut-off level or higher), refer the patient for further examinations.

Other laboratory tests

  • Acute stretching of the right ventricle may lead to myocardial damage and increased concentrations of cardiac markers (TnT, TnI). BNP and proBNP levels may also be elevated.
  • Basic blood count with platelet count, creatinine (GFR 2), ALT, INR (before starting warfarin)
  • CRP is often increased.
  • Thrombophilia screening; indications; see Deep vein thrombosis Deep Vein Thrombosis.

Arterial blood gas analysis

  • To be done depending on the clinical picture; not a routine test.
  • Low partial pressure of oxygen in arterial blood (PaO2 less than 9 kPa) is a common finding in patients with pulmonary embolism.
  • 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.

ECG

  • A normal ECG recording does not exclude PE.
  • ECG changes
    • are dependent on the degree of right heart strain, i.e. the size of the embolus
    • vary over time.
  • The most common ECG changes are:
    • sinus tachycardia
    • T wave inversion in chest leads (V1-V3)
    • partial RBBB or SIQIII pattern.

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 detect right ventricular strain.
    • A normal finding is usually sufficient to exclude the possibility of PE.
  • A single subsegmental embolism represents an uncertain finding.
  • Requires use of a contrast medium (check plasma creatinine).

Ultrasonography of the lower extremities

  • Not suitable for excluding PE.
  • Particularly if CT is contraindicated due to the use of contrast medium or due to radiation exposure, ultrasonography of the legs should be the first choice.
  • The investigation is indicated if there are signs of lower limb venous thrombosis.
  • Local availability and resources determine the order of investigations.
  • If ultrasonography is used as the first-line imaging study, PE can be diagnosed merely by the presence of typical clinical presentation and positive ultrasonography findings. Even if so, right ventricular strain should be assessed by ultrasonography to guide treatment.

Perfusion scan (nuclear scan)

  • A perfusion scan is rarely indicated.
    • A perfusion scan can be carried out if CT angiography is contraindicated due to the use of contrast medium.
    • As the radiation exposure from CT has decreased, no particular benefit is achieved in terms of radiation exposure if both perfusion and ventilation scans are performed.
  • A circulatory disturbance caused by an embolus will show up as a perfusion defect.
  • Simultaneous ventilation scanning is usually necessary (except, for example, in young pregnant women in whom the ventilation scanning would unnecessarily increase the radiation exposure).
  • The result is significant only if it is is clearly positive or clearly negative.
  • Interpretation is hindered by
    • asthma
    • COPD
    • parenchymal diseases.

Chest x-ray

  • A plain chest x-ray is usually normal unless the patient has pulmonary infarction, which is usually signified by a wedge-shaped consolidation.
  • Usually taken to exclude other causes.

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.

Treatment Outpatient Treatment for Acute Pulmonary Embolism

Treatment of circulatory shock

  • Cautious i.v. fluid therapy
    • 200-500 ml of NaCl 0.9% or Ringer's solution / 20-30 minutes
  • If necessary, noradrenaline to raise blood pressure
  • Adequate oxygenation; oxygen supplementation if SaO2< 90%.
  • Thrombolytic therapy or mechanical embolectomy.
  • Extracorporeal membrane oxygenation (ECMO) should be considered in patients with refractory shock.

Choice of treatment

  • A PE with high risk of death, leading to haemodynamic collapse and hypotension should be treated with thrombolysis whereas haemodynamically stable patients should be treated with anticoagulants.
  • If thrombolysis is ineffective or contraindicated, invasive catheter treatment should be considered.
  • Based on risk assessment, patients can be placed in a monitoring unit or on a hospital ward.
  • If echocardiography shows signs of right heart strain, thrombolysis may be considered should the patient's haemodynamics worsen during the antiocoagulant therapy.
  • A small PE does not cause circulatory problems.
  • PE older than 2 weeks does not warrant thrombolysis.
  • If the clinical picture is dominated by a massive lower limb DVT, it is essential to treat the DVT Deep Vein Thrombosis.
  • The usual contraindications to thrombolysis apply.
  • For patients with a low death risk, the possibilities for home care should be assessed. If there are no other indications for hospital treatment, the patient is supported by family or other close persons and lives within easy reach of a hospital, the patient can be discharged from emergency services or after a brief follow-up of 1-2 days on a hospital ward.

Anticoagulant therapy Oral Direct Thrombin Inhibitors or Oral Factor Xa Inhibitors for the Treatment of Pulmonary Embolism

Thrombolytic therapy (fibrinolytic therapy) Thrombolytic Therapy in Pulmonary Embolism

  • The primary choice is alteplase in a routine 100 mg dose: first a 10-mg bolus dose and then 90 mg by constant rate infusion over 2 hours.
    • The total dose for a person weighing less than 65 kg should not exceed 1.5 mg/kg.
  • In case of extreme haemodynamic emergency (such as cardiac arrest), accelerated alteplase treatment can be considered: infusion of 0.6 mg/kg over 15 minutes (total dose not exceeding 50 mg).
  • Low molecular weight heparin (LMWH) should be started simultaneously with thrombolytic therapy.
  • LMWH should be continued until switching over to an oral anticoagulant.

Invasive catheter treatment or surgical management

  • If thrombolysis fails to improve the patient's clinical condition or as an alternative to thrombolysis, percutaneous mechanical fragmentation of the embolus with a catheter, local thrombolytic therapy or, in special cases, surgical embolectomy may be considered on a case by case basis.

Inferior vena cava filter (IVC filter) Vena Caval Filters for the Prevention of Pulmonary Embolism

  • 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 no longer applies. Such a filter is rarely indicated.
  • The filter must be removed as soon as possible, and no later than after 2 weeks.

Discharge and further treatment

  • See Deep vein thrombosis; treatment Deep Vein Thrombosis.
  • It is important for patients to gradually resume their normal physical exercise to maintain their physical performance.
  • If right heart strain has been observed in a patient with PE, flying and physical exercise should be done with caution within the first few weeks.
  • To ensure restored exercise tolerance earlier than this, screening based on proBNP or BNP or earlier echocardiography can be considered particularly if the physical strain (work or sports) would be heavy.
  • In patients with a low risk of death, the situation may improve within a few days and physical activity can therefore be increased quite quickly.
  • A follow-up visit after 6 months should be arranged in primary care for all patients, or earlier if the duration of anticoagulant therapy is shorter than 6 months. At the visit, the following should be assessed:
    • General health and recovery (performance, dyspnoea)
    • Results of thrombophilia tests and other aetiological tests if such tests were considered indicated; see Evaluation of Thrombophilia
    • Decision whether to stop or to continue anticoagulant treatment (instructions by specialized care and consultation, as necessary).
  • If the patient's pulmonary artery pressure was initially significantly elevated, the follow-up visit should include checking of the proBNP or BNP level and ECG.
  • Some patients may continue to have symptoms, and their performance capacity may remain impaired, i.e. they may develop what is called the postpulmonary embolism syndrome even if their NT-proBNP/BNP and/or echocardiography results are normal.

    References

    • [Deep vein thrombosis and pulmonary embolism]. A Current Care Guideline. Working group appointed by the Finnish Medical Society Duodecim, the Finnish Society of Anaesthesiologists, and the Finnish Cardiac Society. Helsinki: Finnish Medical Society Duodecim, 2023 (accessed 17.1.2024). Available in Finnish at http://www.kaypahoito.fi/hoi50022/.
    • Ortel TL, Neumann I, Ageno W, et al. American Society of Hematology 2020 guidelines for management of venous thromboembolism: treatment of deep vein thrombosis and pulmonary embolism. Blood Adv 2020;4(19):4693-4738 [PubMed]
    • Konstantinides SV, Meyer G, Becattini C et al. 2019 ESC Guidelines for the diagnosis and management of acute pulmonary embolism developed in collaboration with the European Respiratory Society (ERS). Eur Heart J 2020;41(4):543-603. [PubMed]