*Pulmonary Embolism

Chapter: Pulmonary Embolism
McMaster Section Editor(s): James Douketis
Section Editor(s) in Interna Szczeklika: Krystyna Zawilska, Anetta Undas, Wiktoria Leśniak
McMaster Author(s): James Douketis
Author(s) in Interna Szczeklika: Piotr Pruszczyk, Adam Torbicki
Additional Information

Definition, Etiology, Pathogenesis Top

Pulmonary embolism (PE) refers to the occlusion of the pulmonary artery or some of its branches by an embolus. The embolus may be formed by thrombi (the most frequent cause of PE; these usually originate from deep veins of the lower extremities or the pelvis, less commonly from veins of the upper parts of the body; this type of PE is a clinical manifestation of deep vein thrombosis [DVT]), or occasionally by amniotic fluid, air (during insertion or removal of a central venous catheter), fat (after a long bone fracture), tumor cells (eg, renal cancer), or a foreign body (eg, material used for embolization procedures).

Risk factors for PE are the same as in the case of DVT (see Deep Vein Thrombosis). In approximately a half of all cases no risk factors are identified (idiopathic PE).

Complications of PE (their severity depends on the size of the embolus and individual cardiovascular reserve):

1) Ventilation-perfusion mismatch leading to impairment of gas exchange and subsequent hypoxemia (it may be aggravated by a shunt of poorly oxygenated blood from the right to the left atrium via a patent foramen ovale).

2) An increase in pulmonary vascular resistance (aggravated by vasoconstriction due to hypoxemia) results in increased right ventricular afterload, right ventricular dilation, a decrease in left ventricular filling, a reduction in cardiac output, hypotension/shock, and impaired coronary blood flow, eventually leading to acute ischemia and injury to the overloaded right ventricle. Impairment of coronary blood flow may cause myocardial injury or even a transmural myocardial infarction with normal coronary arteries, and irreversible progressive right ventricular failure is one of the major causes of death. In patients with heart failure, occlusion of even a small proportion of the pulmonary artery branches may result in shock, whereas in young and otherwise healthy individuals, a substantial occlusion of the pulmonary vascular bed may cause only minor clinical symptoms. Emboli in the peripheral branches of the pulmonary arteries may lead to lung infarcts and focal atelectasis. An increase in right atrial pressure may cause opening of the foramen ovale (this is anatomically patent in approximately a third of the healthy population), thus allowing a venous thrombus to pass and embolize into the systemic circulation (paradoxical embolism). After hemodynamic stabilization, a gradual recanalization of the pulmonary arteries takes place; in rare cases, the emboli do not dissolve despite adequate treatment and slowly undergo organization, which may lead to the development of chronic pulmonary hypertension.

Clinical Features and Natural History Top

1. Symptoms often have a sudden onset and include dyspnea (in ~80% of patients), chest pain (~50%; usually with features of pleural pain, less commonly resembling coronary pain [10%]), cough (20%, usually dry), less frequently collapse or syncope and hemoptysis.

2. Signs: More than half of patients develop tachypnea and tachycardia. In the case of right ventricular dysfunction, the signs include dilation of the jugular veins, a loud pulmonary component of the second heart sound, sometimes a tricuspid regurgitation murmur, hypotension, and signs of shock.

3. Natural history: Symptoms of DVT occur in an approximately one-fourth of patients. Mortality in untreated PE depends on the clinical severity of the disease (see Diagnostic Workup, below) and is up to 30%.

Diagnosis Top

Diagnostic Tests

1. Blood tests: Increased serum D-dimer levels; in the majority of patients with high-risk or intermediate-risk PE, elevated levels of cardiac troponins and/or natriuretic peptides (B-type natriuretic peptide [BNP] or N-terminal pro–B-type natriuretic peptide [NT-proBNP]) are seen, which are indicative of right ventricular overload.

2. Electrocardiography (ECG): Tachycardia; supraventricular arrhythmias as well as nonspecific ST-segment and T-wave changes (typically inverted T waves in leads III and V1-V2) may also occur. Rare features include SIQIIITIII syndrome, right axis deviation, and incomplete or complete right bundle branch block. In patients with PE causing hemodynamic instability, negative T waves in leads V2 to V4 and sometimes up to lead V6 are often observed.

3. Chest radiographs may reveal enlargement of the cardiac silhouette, pleural effusion, elevated hemidiaphragm, dilation of the pulmonary artery, atelectasis, and parenchymal opacification.

4. Computed tomography angiography (CTA) allows for an accurate assessment of the pulmonary arteries from the pulmonary trunk to the segmental arteries. Multislice CT (MSCT) also includes the subsegmental arteries (the clinical significance of isolated thrombi in these arteries is controversial). Additionally, CTA reveals interstitial pulmonary lesions.

5. Echocardiography: In patients with high-risk or intermediate-risk PE, this may reveal right ventricular dilation and thinning of the interventricular septum. A characteristic finding is a hypokinetic right ventricular free wall with preserved apical contractility, as well as dilation of the inferior vena cava due to right ventricular failure and right atrial hypertension. Transesophageal echocardiography allows for the visualization of the pulmonary arteries up to the proximal parts of the lobar arteries and thus detects emboli more effectively than transthoracic echocardiography.

6. Ultrasonography of the deep veins of the lower extremities: Compression ultrasonography (CUS) and/or ultrasonography of the entire venous system of the limb may reveal thrombosis.

7. Other studies: Pulmonary ventilation-perfusion (V/Q) scintigraphy is performed less often because of its limited availability and the advantages of CT angiography. However, V/Q scintigraphy provides less radiation exposure than CT angiography and is a first-line test during pregnancy; moreover, it should be considered in women of child-bearing age or other patients who do not have concomitant lung pathology (which can lead to indeterminate test results). Pulmonary angiography is used rarely because of its invasiveness.

Diagnostic Workup

A patient with suspected PE requires a rapid diagnostic workup. The management strategy depends on the patient’s condition and the availability of diagnostic studies.

1. Evaluate the risk of early death:

1) High-risk PE: Symptoms of shock or hypotension (systolic blood pressure [SBP] <90 mm Hg or SBP fall by ≥40 mm Hg lasting >15 minutes, if not caused by arrhythmia, hypovolemia, or sepsis).

2) Non–high-risk PE: No manifestations of shock or hypotension.

a) Intermediate-risk PE: Features of right ventricular dysfunction (observed on echocardiography or CTA; elevated BNP/NT-proBNP levels) or positive markers of myocardial damage (increased levels of troponin T or I). The risk is additionally increased if the features of right ventricular dysfunction and myocardial damage occur simultaneously.

b) Low-risk PE: Absence of the above-mentioned features of right ventricular dysfunction and markers of myocardial damage.

2. Evaluate the clinical probability of PE (eg, using the Wells score [Table 1] or the modified Geneva score [Table 2]) in a patient with non–high-risk PE. In patients with suspected high-risk PE, the clinical probability of PE is usually high. Diagnostic tests can also be used to consider an alternative diagnosis, for instance, ECG may be used to assess for an acute coronary syndrome or acute pericarditis and a chest radiograph may be used to assess for pneumonia or pneumothorax. The exclusion of alternative diagnoses can increase the clinical probability for PE, which requires specific diagnostic testing.

3. Diagnostic tests in patients at high risk with suspected PE: Figure 1. To confirm the diagnosis, perform an urgent CTA or a V/Q lung scan. If CTA or a V/Q scan is unavailable, or if CTA cannot be performed due to the patient’s condition, bedside echocardiography may be helpful in providing indirect evidence for PE (eg, dilated right ventricle, increased pulmonary artery pressure).

4. Diagnostic tests in patients not at high risk with suspected PE: Figure 2.

1) Patients with a low clinical probability of PE: Measure the D-dimer level using a high-sensitivity (~95%) or moderate-sensitivity (~85%) assay. A normal D-dimer level is sufficient to exclude PE and further investigations and treatment are not necessary. If the D-dimer level is elevated, perform CTA; a negative CTA result excludes PE and allows for the safe discontinuation of anticoagulant treatment.

2) Patients with an intermediate clinical probability of PE: Measure the D-dimer level using a high-sensitivity (~95%) assay. A normal D-dimer level is sufficient to exclude PE and further investigations and treatment are not necessary. If the D-dimer level is elevated, perform CTA; a negative CTA result excludes PE and allows for the safe discontinuation of anticoagulant treatment.

3) Patients with a high clinical probability of PE: Measurement of D-dimer levels is not recommended and CTA should be performed. In patients with an indeterminate CTA result, consider a V/Q scan or bilateral CUS to assess for DVT.

The diagnosis of PE in non–high-risk patients is confirmed by a thrombus observed in CTA and extending to the level of the segmental arteries. If the embolism is limited to a single subsegmental artery and there is no evidence of thrombosis elsewhere (eg, lower limb DVT), anticoagulant therapy may not be warranted.

5. Diagnosis of PE in pregnancy: The measurement of D-dimer levels is of limited value because these may be elevated due to pregnancy, particularly in the second half of pregnancy. If the D-dimer is negative, there is insufficient evidence that it can be used to exclude DVT without further diagnostic imaging. The initial diagnostic test is lower extremity venous ultrasonography, because the diagnosis of DVT is sufficient to start anticoagulant therapy without further diagnostic testing for PE. Diagnostic tests involving ionizing radiation should only be performed in pregnant women with normal bilateral lower limb venous ultrasonography. A V/Q scan and CTA can be done during pregnancy, but V/Q scanning is suggested as an initial test because it has been better studied and there is more radiation exposure to the mother with CTA.

Differential Diagnosis

Pneumonia and pleurisy, asthma, chronic obstructive pulmonary disease (COPD), pneumothorax, acute respiratory distress syndrome, heart failure, acute coronary syndrome (eg, in the case of ST-T changes in a patient with chest pain), intercostal neuralgia and other causes of chest pain; and in the case of high-risk PE, also cardiogenic shock, cardiac tamponade, and aortic dissection.

Severe heart failure and exacerbation of COPD are risk factors for VTE and may coexist with PE.

Treatment Top

Treatment of High-Risk Pulmonary Embolism

Treatment of high-risk PE: Figure 1.

1. Start symptomatic treatment:

1) Treat hypotension/shock as in patients with right ventricular failure (see Acute Heart Failure). Note that intensive fluid resuscitation may have harmful effects due to an increase in right ventricular overload.

2) Depending on the presence and severity of respiratory failure, administer oxygen and consider indications for mechanical ventilation.

2. Intravenous unfractionated heparin (UFH): Administer UFH immediately at a loading dose of 80 U/kg (up to 5000 U) as an IV bolus provided that anticoagulant treatment is not contraindicated (see Heparins).

3. Thrombolytic therapy: Thrombolytic therapy is suggested if not contraindicatedEvidence 1Weak recommendation (benefits likely outweigh downsides, but the balance is close or uncertain; an alternative course of action may be better for some patients). Low Quality of Evidence (low confidence that we know true effects of the intervention). Quality of Evidence lowered due to the risk of bias and imprecision. Kearon C, Akl EA, Comerota AJ, et al; American College of Chest Physicians. Antithrombotic therapy for VTE disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012 Feb;141(2 Suppl):e419S-94S. doi: 10.1378/chest.11-2301. Erratum in: Chest. 2012 Dec;142(6):1698-1704. PubMed PMID: 22315268; PubMed Central PMCID: PMC3278049.(see ST-Segment Elevation Myocardial Infarction) (most contraindications are relative in the case of life-threatening PE, particularly when immediate embolectomy is not possible). Early confirmation of PE using imaging studies is indicated, but in critically ill patients the decision to use thrombolysis can be made solely on the basis of the clinical features suggestive of PE. In some patients, bedside cardiac echocardiography may provide indirect evidence to support a diagnosis of massive PE (right ventricular dilation, elevated pulmonary artery pressure, paradoxical septal motion). In patients with cardiac arrest, the immediate administration of 50 mg of IV alteplase and starting cardiopulmonary resuscitation may be life-saving. Thrombolytic therapy is most effective when administered within 48 hours of the onset of PE symptoms, but may have beneficial effects even after 6 to 14 days.

Dosage of thrombolytic agents:

1) Streptokinase:

a) An accelerated regimen (preferred): 1.5 million U IV over 2 hours.

b) A standard regimen: 250,000 U IV over 30 minutes followed by 100,000 U/h.

2) Recombinant tissue plasminogen activator (rtPA) (alteplase):

a) A standard regimen: 100 mg IV over 2 hours.

b) An accelerated regimen: 0.6 mg/kg (maximum 50 mg) over 15 minutes.

4. If the patient has not received heparin prior to the administration of the thrombolytic agent, administer IV UFH 80 U/kg (up to 5000 U) and then start a continuous infusion of UFH at a rate of 18 U/kg/h (up to 1300 U/h) while monitoring the activated partial thromboplastin time (aPTT). If a loading dose of UFH has been used before the thrombolytic agent, you may continue the UFH infusion together with an infusion of the thrombolytic agent or start UFH after the discontinuation of the agent. Evidence is lacking in regards to whether UFH should be continued during the concurrent administration of thrombolytic therapy; it is suggested that UFH not be coadministered during thrombolytic therapy.

5. Once thrombolytic treatment has been discontinued, with the patient stabilized while still receiving heparin, start a VKA following the same principles as in DVT (see Deep Vein Thrombosis).

6. In the case of contraindications to anticoagulant treatment in patients at high risk of PE recurrence, ie, with extensive proximal DVT, consider placement of an inferior vena caval filter. The filter is inserted via the femoral vein or the internal jugular vein and placed in the inferior vena cava, below the ostia of the renal veins. This treatment is sometimes also indicated in selected patients with severe pulmonary hypertension (to protect against even a minor PE episode, which in this situation could be life-threatening) or after pulmonary embolectomy. If the risk of bleeding has decreased, start anticoagulant treatment and remove the filter. Do not place the inferior vena caval filter in patients receiving anticoagulant treatment.

7. If thrombolytic therapy is contraindicated or has been ineffective (hypotension or shock persist), as well as in the case of a mobile thrombus in the right ventricle or right atrium (particularly passing through the foramen ovale), consider pulmonary embolectomy (surgical removal of the thrombus from the pulmonary arteries, performed using extracorporeal circulation). In the case of a thrombus located proximally in the pulmonary arteries, you can also consider percutaneous embolectomy or fragmentation of the thrombus using a catheter. Such interventions should only be considered in experienced specialized centers.

Treatment of Low-Risk Pulmonary Embolism

1. In all patients with suspected PE, start anticoagulant treatment while still waiting to perform diagnostic tests if the results cannot be obtained within 24 hours. In patients with a high or intermediate clinical probability of PE, start anticoagulant treatment immediately, without waiting for the results of diagnostic tests.

2. Anticoagulant treatment regimen: As in DVT (see Deep Vein Thrombosis). 

Treatment of Intermediate-Risk Pulmonary Embolism

The treatment is the same as in patients with low-risk PE, but in patients with right ventricular overload and myocardial dysfunction it should be started in a clinical setting with continuous monitoring of heart rate and blood pressure. In case of clinical deterioration, start “rescue” thrombolytic treatment, and if this is contraindicated, perform embolectomy or percutaneous intervention, depending on the clinical setting and availability.

Treatment of Pulmonary Embolism in Pregnancy

1. Non–high-risk PE: Treatment as in DVT (see Deep Vein Thrombosis).

2. High-risk PE: If this is life-threatening for the pregnant patient, consider thrombolytic therapy (it may cause bleeding into the placenta and lead to miscarriage). Pulmonary embolectomy is also associated with a high risk for both the child and the mother.

Duration of Treatment

As in DVT (see Deep Vein Thrombosis). While continuing treatment with heparin, consider switching from UFH to LMWH or fondaparinux.

Prevention Top

1. See Primary Prevention of Venous Thromboembolism.

2. Prevention of recurrent VTE: see Deep Vein Thrombosis.

Tables and FiguresTop

Table 1. Assessment of the clinical probability of pulmonary embolism using the Wells score

Parameter

Score

Predisposing factors

History of DVT or PE

1.5

Recent surgery or immobilization

1.5

Cancer

1

Symptoms: Hemoptysis

1

Signs

Heart rate >100 beats/min

1.5

Signs and symptoms of DVT

3

Clinical assessment: Alternative diagnosis less likely than PE

3

Interpretation

Clinical probability (3 levels)

Low clinical probability: Total score 0-1

Intermediate clinical probability: Total score 2-6

High clinical probability: Total score ≥7

Clinical probability (2 levels)

PE not likely: Total score 0-4

PE likely: Total score >4

DVT, deep vein thrombosis; PE, pulmonary embolism.

Table 2. Assessment of the clinical probability of pulmonary embolism using the revised Geneva score

Parameter

Score

Predisposing factors

Age >65 years

1

Previous deep vein thrombosis or pulmonary embolism

3

Surgery or fracture in the past month

2

Active malignant condition

2

Symptoms

Unilateral lower limb pain

3

Hemoptysis

2

Signs

Heart rate 75-94 beats/min

3

Heart rate ≥95 beats/min

5

Pain on deep venous palpation of the lower limb and unilateral edema

4

Interpretation

Clinical probability (3 levels)

Low clinical probability: Total score 0-3

Intermediate clinical probability: Total score 4-10

High clinical probability: Total score ≥11

Figure 1. Management algorithm in patients with high-risk pulmonary embolism.

Figure 2. Management algorithm of non–high-risk pulmonary embolism.

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