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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 and 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 PESI or sPESI risk classification, for example (Table T1). Based on this, patients can be divided into classes with moderate (PESI III-V or sPESI ≥ 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 based on the PESI1 and sPESI2 scores. Source: Finnish Current Care Guideline on deep vein thrombosis and pulmonary embolism, 2016 (modified).

CriterionPESIsPESI
Age1 per year of age>80 years of age = 1
Male sex10
Malignancy301
Heart failure10
1
Lung disease10
Heart rate ≥ 110/min201
Systolic blood pressure < 100 mmHg301
Respiratory rate ≥ 30/min20
Body temperature < 36°C20
Lowered level of consciousness, confusion60
Oxygen saturation < 90% with indoor air201
Interpretation
PESI score Class30-day risk of death
<65 pointsI: Very low risk0-1.6 %
66-85 pointsII: Low risk1.7-3.5 %
86-105 pointsIII: Moderate risk3.2-7.5 %
106-125 pointsIV: High risk4.0-11.4 %
>125 pointsV: Very high risk10.0-24.5 %
sPESI score
0 pointsLow mortality risk1.1 %
≥point or moreHigh mortality risk8.9 %
Lähteet:
1 Aujesky D, Obrosky DS, Stone RA ym. Derivation and validation of a prognostic model for pulmonary embolism. Am J Respir Crit Care Med 2005;172(8):1041-6. [PubMed]
2 Jiménez D, Aujesky D, Moores L ym. 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]
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 on circulatory compensation capacity.
  • 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

A clinical model for the assessment of the probability of pulmonary embolism

VariableScore
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/PE1.5
Haemoptysis1.0
Cancer (treatment ongoing, within 6 months or palliative)1.0
Clinical probability of PESum
Low (probability 10%)<2.0
Moderate (probability 30%)2.0-6.0
High (probability 65%)>6.0
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]
Investigation and treatment strategy in suspected PE D-Dimer Testing and Pulmonary Embolism
  • 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 leg veins.
  • If the pretest probability is low or moderate, the D-dimer test is indicated. If the D-dimer level is significantly elevated (see below), hospital investigations are warranted and LMWH should be started before imaging.

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

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 PE.
  • A single subsegmental embolism represents an uncertain finding.
  • Requires use of a contrast medium (check plasma creatinine).

Ultrasonography of the legs

  • 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, pulmonary embolism 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.

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 D-Dimer Testing and Pulmonary Embolism

  • 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 plasma D-dimer concentration lower than cut-off value (see below) does nevertheless exclude PE in a patient with low or moderate pretest probability. In such a case, no further investigations are necessary.
  • 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 examination.

Other laboratory tests

  • Acute stretching of the right ventricle may lead to myocardial damage and increased concentrations of cardiac markers (TnT, TnI). Also BNP and NT-proBNP levels may be elevated.
  • Basic blood count with platelet count, creatinine (GFR Gfr Calculator), ALT, INR/PT ( APTT testing to screen for any coagulation disorder is also recommended)
  • Thrombophilia screening, indications; see Deep vein thrombosis Deep Vein Thrombosis.

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.

ECG

  • A normal ECG 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 S1QIII 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.

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.

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 is be treated with anticoagulants.
  • 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.
  • Reteplase or tenecteplase can be used instead of alteplase.
  • Low molecular weight heparin (LMWH) should be started simultaneously with thrombolytic therapy.
  • LMWH should be continued until switching over to an oral anticoagulant.

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.
  • 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.
  • The filter must be removed as soon as possible, and no later than after 2 weeks.

Invasive 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 surgical embolectomy may be considered on a case by case basis.

Further treatment

  • See Deep vein thrombosis; treatment Deep Vein Thrombosis.
  • 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.
    • General health and recovery
    • 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 NT-proBNP or BNP level.
  • Some patients may continue to have symptoms, and their performance capacity may remain impaired, i.e. they may develop what is called the postembolic syndrome even if their Nt-proBNP/BNP and/or echocardiography results are normal.

References

  • 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]
  • Righini M, Van Es J, Den Exter PL et al. Age-adjusted D-dimer cutoff levels to rule out pulmonary embolism: the ADJUST-PE study. JAMA 2014;311(11):1117-24. [PubMed]
  • Kearon C, de Wit K, Parpia S et al. Diagnosis of Pulmonary Embolism with d-Dimer Adjusted to Clinical Probability. N Engl J Med 2019;381(22):2125-2134. [PubMed]

Evidence Summaries ⬆