• Clinical science

Pulmonary embolism

Abstract

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.

Epidemiology

  • Accounts for ∼ 100,000 deaths in the US per year.
  • Incidence rises with age.
  • Sex: >

References:[1]

Epidemiological data refers to the US, unless otherwise specified.

Etiology

references:[1][2]

Pathophysiology

Further confounding factors of gas exchange

  • Release of vasoactive substances from the embolism

References:[3][1]

Clinical features

  • 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
  • Symptoms of DVT: unilaterally painful leg swelling

Consider PE as a differential diagnosis in recurring or progressive dyspnea of uncertain etiology!

Under anesthesia during surgery

  • Increasing heart rate
  • Drop in blood pressure
  • Drop in partial pressure of end-tidal CO2 (PetCO2) in capnography.
  • Drop in PaO2 saturation end

References:[4]

Subtypes and variants

Pulmonary embolism during pregnancy, childbirth, and the postpartum period

  • Diagnostic problems
    • Elevated D-dimer levels are not sufficient for diagnosis
    • Imaging
      • Protective measures should be taken to avoid fetal exposure to radiation
        • If there are clinical signs of PE, Doppler ultrasound evidence of DVT usually suffices to secure diagnosis.
        • Perfusion scintigraphy with low-dose radiation preferred over CTA in imaging of the mammary region
        • CTA is possible but a relatively high dose of radiation cannot be prevented.
  • Special considerations for treatment
    • Anticoagulation throughout pregnancy and for 6–12 weeks after delivery (for a a minimum of 3 months in total); see also therapeutic anticoagulation during pregnancy
    • Interventional methods are preferred if recanalization is indicated.
    • Placement of a vena cava filter should be considered in cases with high risk of hemorrhage where anticoagulation is not (yet) possible.

Pregnancy increases the risk of PE by a factor of 4!

Diagnostics

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), administer immediate anticoagulation with unfractionated heparin 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)

Wells criteria for pulmonary embolism

  • 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 Wells criteria for DVT).
Wells score Points
Clinical symptoms of DVT 3
PE more likely than other diagnoses 3
Previous PE/DVT 1.5
Tachycardia (heart rate > 100/min) 1.5
Surgery or immobilization in the past four weeks 1.5

Hemoptysis

1
Malignancy (being treated, in palliative care or diagnosis less than 6 months ago) 1
Wells criteria (clinical probability)
  • Total score of 0–1: low probability of PE (∼ 10%)
  • Total score of 2–6: moderate probability of PE (∼ 30%)
  • Total score of > 6: high probability of PE (∼ 65%)

Modified/simplified Wells criteria (clinical probability)

  • Total score of > 4: PE likely
  • Total score of ≤ 4: PE unlikely

Blood analysis

  • 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.

Imaging

  • 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
  • Chest radiograph
  • Echocardiography: to detect right atrium pressure (RAP) signs
  • Ventilation/perfusion scintigraphy
    • 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
    • Assessment
      • Perfusion failure in normally ventilated affected pulmonary area (mismatch) suggests PE
      • Evidence of normal lung perfusion rules out PE → ventilation scintigraphy superfluous
  • Pulmonary angiography
    • Indications: only conducted if CT angiography unavailable
    • Procedure: right heart catheterization → insertion of a catheter into a pulmonary arteryradiograph after administration of contrast agent

Other diagnostic measures

  • Electrocardiography (ECG)
    • Sinus tachycardia most commonly seen
    • Signs of right ventricular pressure overload
      • SIQIIITIII -pattern
      • New right bundle branch block
      • Bradycardia < 50 or tachycardia > 100 bpm
      • Right or extreme right axis deviation (30% of cases)
      • P-pulmonale (∼10% of cases)
      • ST-segment changes
      • T negativity in leads V2and V3 (∼ 30%)
      • Atrial arrhythmias: especially extrasystoles
  • Compression Doppler ultrasound: diagnosis of potential underlying deep vein thrombosis
  • Diagnostics for underlying cause

References:[5][4][6][3]

Risk stratification

sPESI and PESI
Criteria Points
sPESI

PESI

Age + 1 if > 80 years + 1 per year
History of cancer 1

+ 30

Systolic blood pressure < 100 mm Hg 1

+ 30

Heart rate ≥ 110 bpm 1 + 20
O2 saturation on room air < 90% 1 + 20
Heart failure 1 + 10
Chronic lung disease + 10
Altered mental status Not considered + 60
Temperature < 96.8°F + 20
Respiratory rate > 30/min + 20
Sex

Male: + 10

Female: 0

  • Combination of sPESI, laboratory tests, and imaging
Clinical risk Risk criteria and scores
Shock, hypotension sPESI ≥ 1 Right ventricular pressure overload Cardiac biomarkers Therapeutic consequences
High + + + + High-risk patient; recanalization is likely necessary
Medium–high - + + + At-risk patient → intensive care treatment and close monitoring → prepare for potentially necessary recanalization
Medium–low - + Max. 1 criterion positive Moderate risk patient → close clinical monitoring necessary (intermediate care may be necessary)
Low - - - - Normal in-patient treatment usually sufficient

Treatment

Acute management

General measures

  • 45° reclining sitting posture
  • Oxygen supplementation and intubation if respiratory failure
  • IV fluids; and/or vasopressors in patients with hypotension
  • Analgesics and sedatives

Specific measures

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)!

  1. Initial anticoagulation (0–10 days)
  2. Long-term anticoagulation and prophylaxis (3–6 months)

Massive, life-threatening pulmonary embolism: recanalization

  • Thrombolytic therapy
    • Indications
      • In cases of massive PE causing right heart failure
      • In hemodynamically unstable patients requiring resuscitation
      • Alternative to PTCA for patients with STEMI if PTCA cannot be performed within 90–120 minutes (see “Treatment algorithm based on ECG findings” in the acute coronary syndrome learning card)
      • Preclinical thrombolysis
    • Procedure: fibrinolysis, preferably with recombinant tissue-type plasminogen activator (tPA), e.g., alteplase
      • Most commonly systemic infusion via IV catheter
      • Alternatively, direct infusion of tPA into pulmonary artery via pulmonary arterial catheter
      • Administration of anticoagulants discontinued during thrombolysis
    • Complications
      • Risk of hemorrhage during thrombolytic treatment
      • Observe contraindications for thrombolytic therapy
  • Embolectomy
    • 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!

Further measures

  • Inferior vena cava filter
    • Indications
      • In recurrent DVTs despite anticoagulation
      • If anticoagulation is contraindicated (e.g., high-risk of bleeding) in patients with a documented lower leg DVT
  • DVT prophylaxis: (subcutaneous heparin or LMWH for all immobile patients, early ambulation, and compression stockings)

References:[7][5][3][8]

Complications

  • High risk of recurrence: without anticoagulant treatment ∼ 10% in the first year, ∼ 5% per year after
  • Right ventricular failure
  • Atelectasis (∼ 20% of cases)
  • Pulmonary effusion
  • Pulmonary infarction (∼ 10% of cases)
    • Embolisms of smaller segmental arteries can lead to wedge-shaped hemorrhagic pulmonary infarctions
    • Right ventricular failure, increased bronchial venous pressure, and preexisting pulmonary diseases increase the risk.
  • Pneumonia from pulmonary infarction: peripheral infiltration on chest X-ray (typically wedge-shaped = Hampton's hump)

References:[1][9]

We list the most important complications. The selection is not exhaustive.

Differentials