Evidence-Based Medicine

Pulmonary Embolism (PE)

Pulmonary Embolism (PE)

Background

  • Pulmonary embolism represents a mechanical obstruction of 1 or more branches of the pulmonary vasculature, usually due to a blood clot (thromboembolism) from deep vein thrombosis (DVT).
  • Less common types of emboli include septic emboli, venous air emboli, tumor emboli, and fat emboli.
  • The annual incidence of PE is about 60 per 100,000, although it may be lower in Asian populations.
  • Risk factors for venous thromboembolism (VTE), including PE in hospitalized patients, include prior VTE, thrombophilia, surgery, cancer, pregnancy, immobilization, trauma, obesity, and central venous access.
  • Complications of pulmonary embolism include arrhythmia, chronic thromboembolic pulmonary hypertension, and cor pulmonale which may lead to obstructive shock.
  • Consideration for prevention of VTE including PE is critically important in both medical and surgical patients.

Evaluation

  • Suspect PE in patients with dyspnea, tachypnea, tachycardia, pleuritic chest pain, cough, and/or fever and perform PE-focused history and evaluation.
  • The work-up for PE varies depending on whether patient presents as hemodynamically stable or unstable.

Suspected Pulmonary Embolism With Sustained Hypotension

  • Patients with pulmonary embolism and persistent hypotension are at high risk of early mortality.
  • In unstable patients perform an emergency computed tomography (CT) angiography to detect the PE or a bedside transthoracic echocardiography to assess for right ventricular dysfunction or overload, depending on availability and clinical circumstance (Strong recommendation).
  • In high-risk PE patients with signs of right ventricular dysfunction on transthoracic echocardiography who are too unstable to have a CT angiography, consider compression venous ultrasonography and/or a transesophageal echocardiography (TEE) in intubated patients for bedside search for venous and/or pulmonary artery thrombi if immediately available (Weak recommendation).
  • In unstable patients when acute coronary syndrome has been excluded, consider performing a pulmonary angiography (Weak recommendation).

Suspected Pulmonary Embolism Without Sustained Hypotension

  • Assess the pretest probability of PE using a validated clinical decision tool or clinical logic (Strong recommendation).
  • If the clinical probability of PE is high:
    • Perform multidetector CT (Strong recommendation).
    • Consider ventilation/perfusion (V/Q) scan (Weak recommendation).
    • Do not perform D-dimer testing (Strong recommendation).
  • If the clinical probability of PE is low:
    • assess Pulmonary Embolism Rule-Out Criteria (PERC)
      • If patients meet all PERC criteria, the probability is low and no further testing is needed.
      • If patients do not fulfill all 8 PERC criteria, perform a D-dimer test.
  • If the clinical probability of PE is intermediate, perform an age-adjusted D-dimer (Strong recommendation).
  • Results of D-dimer test in low- or intermediate-risk patients
    • If the D-dimer is negative, no further testing is needed (Strong recommendation).
    • If the D-dimer is positive and the clinical probability of PE is low or intermediate, use 1 or more of the following tests to evaluate for possible PE:
      • multidetector CT looking for a segmental or more proximal thrombus (Strong recommendation)
      • V/Q lung scan (Weak recommendation)
  • Consider pulmonary angiography in patients of any risk (low, intermediate, or high) when there is a discrepancy between clinical evaluation and the results of noninvasive imaging tests (Weak recommendation).

Further Evaluation After the Diagnosis is Made

  • Risk stratification is based on the presence of shock and other clinical factors and helps identify patients with PE who are at high risk of early hemodynamic instability and death. It helps direct treatment, including potential outpatient management of hemodynamically stable patients at low risk.
  • Classifications of PE include:
    • Massive or high-risk: the PE is causing hemodynamic instability.
    • Submassive or intermediate risk: the PE is causing cardiac dysfunction with right ventricular strain (echocardiographic findings may include right ventricular hypokinesis or dilation, tricuspid regurgitation, and/or paradoxic septal movement), frequently with elevations in troponin and/or brain natriuretic peptide (BNP).
    • Low risk: absence of any signs of massive or submassive PE.
  • Order a complete blood count, activated partial thromboplastin time (aPTT), and prothrombin time (PT)/INR to establish baseline hematologic values before anticoagulation therapy unless hemodynamic instability requires immediate empiric anticoagulation therapy.
  • Because the presence of a diagnosable thrombophilia usually does not change the duration or intensity of anticoagulation, thrombophilia testing should be avoided in most patients with VTE (including unprovoked VTE).
  • Patients with unprovoked VTE should undergo age-appropriate cancer screening.

Management

Initial Treatment

Stable Patients

  • Administer anticoagulant without delay while awaiting results of diagnostic tests in patients with high or intermediate clinical probability of PE (Strong recommendation).
  • Consider not administrating anticoagulant for patients at low clinical suspicion of PE while awaiting results of diagnostic tests, provided test results are expected within 24 hours (Weak recommendation).
  • Administer an anticoagulant for patients with diagnosed PE (Strong recommendation).
  • Consider early discharge with home treatment in carefully selected patients with low-risk PE if appropriate outpatient care and anticoagulant treatment can be provided (Weak recommendation).
  • Direct oral anticoagulants (DOACs) are recommended over vitamin K antagonist (VKA) therapy unless contraindications are present (Strong recommendation).
  • DOAC therapy may include:
    • DOACs where no initial parenteral anticoagulation is needed
      • rivaroxaban (Xarelto) - 15 mg twice daily for 3 weeks (followed by 20 mg once daily dosing; avoid if creatinine clearance [CrCl] < 15 mL/minute)
      • apixaban (Eliquis) 10 mg orally twice daily for 7 days, then 5 mg twice daily
      • avoid rivaroxaban and apixaban if CrCl < 15 mL/minute and use with caution if CrCl 15-29 mL/minute
    • DOACs where 5-10 days of initial parenteral anticoagulant is needed prior to use
      • dabigatran (Pradaxa) - 150 mg twice daily (avoid if CrCl < 30 mL/minute)
      • edoxaban (Savaysa or Lixiana) - 60 mg once daily (30 mg once daily if CrCl 15-50 mL/minute, if body weight ≤ 60 kg [132.28 lbs], or with concomitant use of certain p-glycoprotein inhibitors)
  • If therapy other than a DOAC is desired, available options include:
    • parenteral anticoagulants in combination with VKA, which may include:
      • low-molecular-weight heparin (LMWH)
        • dosing regimens include:
          • enoxaparin (Lovenox) 1 mg/kg subcutaneously every 12 hours (inpatient or outpatient treatment) or 1.5 mg/kg subcutaneously once daily (inpatient treatment)
          • tinzaparin (Innohep) 175 anti-Xa units/kg subcutaneously once daily
          • dalteparin (Fragmin) 100 units/kg subcutaneously every 12 hours or 200 units/kg subcutaneously once daily (maximum dose 18,000 units daily)
        • for patients with CrCl < 30 mL/minute, dose reduction, coagulation monitoring, or avoiding use of LMWH may be considered
      • fondaparinux (Arixtra) 5-10 mg subcutaneously once daily based on weight (use contraindicated in patients with CrCl < 30 mL/minute)
      • LMWH and fondaparinux are suggested over IV unfractionated heparin (UFH) (Strong recommendation)
      • IV UFH 80 units/kg IV bolus then 18 units/kg/hour, then adjusted by coagulation monitoring to target activated partial thromboplastin time (aPTT) 1.5-2.5 times normal
      • deep subcutaneous UFH initial dose is 333 units/kg then 250 units/kg twice daily
    • Administer a VKA with parenteral anticoagulation until an INR of 2-3 is achieved (Strong recommendation).
    • Start VKA early (same day as parenteral anticoagulation) and for at least 5 days and until INR ≥ 2 for at least 24 hours (Strong recommendation).

High-risk (Previously Referred to as Massive Pulmonary Embolism) Patients with Hemodynamic Instability Such as Shock or Hypotension

  • Treat for shock if necessary.
  • Use IV UFH in patients with high-risk PE with shock or hypotension (Strong recommendation).
  • Thrombolytic therapy
    • Systemic thrombolysis:
      • is not recommended for most patients without hypotension (Strong recommendation)
      • is recommended in patients without high bleeding risk who are hemodynamically unstable (Strong recommendation)
      • should be considered in intermediate-high-risk (previously referred to as submassive) patients if clinical signs of hemodynamic decompensation occur (Weak recommendation)
      • is preferred over catheter-directed thrombolysis (Weak recommendation)
    • Catheter-directed thrombolysis:
      • is suggested in patients with acute hypotensive PE in case of high bleeding risk, failed systemic thrombolysis, and/or shock likely to result in death before systemic thrombolysis takes effect (Weak recommendation)
      • is suggested as an alternative to surgical treatment if systemic thrombolysis is contraindicated or has failed (Weak recommendation)
  • Surgical pulmonary embolectomy
    • Use if shock or hypotension is present and there is a contraindication to or failed thrombolysis (Strong recommendation).
    • Consider if:
      • intermediate-risk (previously referred to as submassive) acute PE with clinical evidence of poor prognosis (Weak recommendation)
      • intermediate-high-risk PE if anticipated bleeding risk with thrombolysis is high (Weak recommendation)

Long-term Anticoagulation

Patients Without Cancer

  • DOACs are recommended over VKA as long-term therapy (Weak recommendation).
  • DOAC therapy may include:
    • apixaban (may be preferred agent due to reduced bleeding compared to VKA therapy)
      • 5 mg twice daily (after initial 10 mg twice daily dosing for 7 days)
      • 2.5 mg twice daily after ≥ 6 months
      • avoid if CrCl < 15 mL/minute and use with caution if CrCl 15-29 mL/minute
    • rivaroxaban
      • 20 mg once daily (after initial 15 mg twice daily dosing for 3 weeks)
      • 10 mg once daily after ≥ 6 months
      • avoid if CrCl < 15 mL/minute and use with caution if CrCl 15-29 mL/minute
    • dabigatran
      • 150 mg twice daily (avoid if CrCl < 30 mL/minute)
      • do not use in patients with severe renal impairment (CrCl < 30 mL/minute)
    • edoxaban
      • 60 mg once daily
      • 30 mg once daily for patients with CrCl 15-50 mL/minute, if body weight ≤ 60 kg (132.28 lbs), or with concomitant use of certain p-glycoprotein inhibitors
  • An oral VKA, such as warfarin with a target INR 2.5 (INR 2-3) may be considered as an alternative to the above medications.
  • Duration of anticoagulant therapy:
    • If provoked PE (trigger identified) with transient risk factor (surgical or nonsurgical), anticoagulate for 3 months (Strong recommendation).
    • If first unprovoked or idiopathic PE (no identified trigger):
      • Anticoagulate for at least 3 months (Strong recommendation).
      • Discontinue anticoagulation after 3 months if high risk of bleeding or secondary to transient/reversible risk factors (Strong recommendation).
      • Consider extended anticoagulant therapy (beyond 3 months) for an indefinite period of time if low-to-moderate bleeding risk (Weak recommendation).
    • If second unprovoked PE:
      • Anticoagulate for at least 3 months (Strong recommendation).
      • Anticoagulate indefinitely unless PE is provoked by major transient or reversible factors or if bleeding risk is high (Strong recommendation).

Patients with Active Cancer

  • Anticoagulation is suggested for an indefinite period or until cancer is cured (Weak recommendation).
  • DOAC agents edoxaban or rivaroxaban are suggested in patients without gastrointestinal cancer (Weak recommendation).
  • Weight-adjusted subcutaneous LMWH is suggested over VKA therapy for first 6 months if DOACs are not an option (Weak recommendation).

Vena Cava Filters

  • Do not use vena cava filters for routine use if an anticoagulant is used (Strong recommendation).
  • Consider if anticoagulant therapy is contraindicated (Weak recommendation).
  • Consider if there is a recurrence of PE despite adequate anticoagulation (Weak recommendation).

Published: 09-07-2023 Updeted: 09-07-2023

References

  1. Konstantinides SV, Meyer G, Becattini C, et al. 2019 European Society of Cardiology Guidelines for the diagnosis and management of acute pulmonary embolism developed in collaboration with the European Respiratory Society (ERS). Eur Heart J. 2020 Jan 21;41(4):543-603
  2. Jaff MR, McMurtry MS, Archer SL, et al; American Heart Association Council on Cardiopulmonary, Critical Care, Perioperative and Resuscitation, American Heart Association Council on Peripheral Vascular Disease, American Heart Association Council on Arteriosclerosis, Thrombosis and Vascular Biology. Management of massive and submassive pulmonary embolism, iliofemoral deep vein thrombosis, and chronic thromboembolic pulmonary hypertension: a scientific statement from the American Heart Association. Circulation. 2011 Apr 26;123(16):1788-830, correction can be found in Circulation 2012 Aug 14;126(7):e104
  3. Goldhaber SZ, Bounameaux H. Pulmonary embolism and deep vein thrombosis. Lancet. 2012 May 12;379(9828):1835-46
  4. Busse LW, Vourlekis JS. Submassive pulmonary embolism. Crit Care Clin. 2014 Jul;30(3):447-73
  5. Raja AS, Greenberg JO, Qaseem A, Denberg TD, Fitterman N, Schuur JD. Evaluation of Patients with Suspected Acute Pulmonary Embolism: Best Practice Advice from the Clinical Guidelines Committee of the American College of Physicians. Ann Intern Med. 2015 Nov 3;163(9):701-11

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