Pulmonary embolism medical therapy

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Editor(s)-In-Chief: The APEX Trial Investigators, C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-In-Chief: Cafer Zorkun, M.D., Ph.D. [2]

Overview

In most cases, anticoagulant therapy is the mainstay of treatment.

Treatment Protocol

Stabilize the patient Respiratory Support Hemodynamic Support Anticoagulation

Initial Treatment options (≤5 Days) Unfractionated heparin Low molecular weight heparin Factor Xa Inhibitors (fondaparinux) Thrombolysis Percutaneous mechanical embolectomy Surgery Vitamin K antagonists

Long term treatment (≥3 Month) Vitamin K antagonists (INR target, 2.0-3.0)

Extended treatment (Indefinite) Vitamin K antagonists (INR target, 2.0-3.0 OR 1.5-1.9)

Anticoagulation

• Subcutaneous or Intravenous Low molecular weight heparin.
  • Hemodynamically stable patients.
• Thrombolysis
  • High Risk Hemodynamically stable patients.
  • Hemodynamically Unstable patients.
• Percutaneous mechanical thrombectomy.
  • High risk patients with absolute contraindications to Thrombolytics.
  • Patients with failed Thrombolysis.
• Low molecular weight heparin is preferred over Vitamin K antagonist.
  • Cancer patients.
  • Pregnant patients.

Dosage

The American College of Cardiology (ACC) Foundation and the American Heart Association (AHA) have proposed the following dosage schedule for the use of thrombolytics:

• Streptokinase

Loading dose:250 000 IU over 30 min. Maintenance dose:100 000 IU/h over 12–24 hr. Accelerated regimen: 1.5 million IU over 2 hr.

• Urokinase

Loading dose:4400 IU/kg over 10 min. Maintenance dose:4400 IU/kg/h over 12–24 hr. Accelerated regimen: 3 million IU over 2 hr.

• Recombinant tissue plasminogen activator (rtPA)

100 mg over 2 hr or 0.6 mg/kg over 15 min (maximum dose 50 mg).

Another validated nomogram has proposed the following dosage.

• Low molecular weight heparin
  • Enoxaparin : 1 mg/Kg body weight (twice daily).
  • Tinzaparin : 175 U/Kg body weight (once daily).

• Factor Xa Inhibitors
  • Fondaparinux :
    • Patient weighing less than 50 Kg (110 lb) : 5 mg (once daily).
    • Patient weighing 50 Kg (110 lb) to 110 Kg (220 lb): 7.5 mg (once daily).
    • Patient weighing more than 100 Kg (220 lb) : 10 mg (once daily).

• Unfractionated heparin
  • Loading Dose: 80 IU/Kg or 5000 IU
  • Mantainace Dose: 18 IU/Kg/Hr to achieve a target aPTT 1.5 to 2.5 times the normal value.

• Thrombolytics
  • In patient with cardiac arrest:
    • Alteplase (FDA-appointed)
      • 50-mg IV bolus
      • May repeat 50-mg IV bolus in 15 min if no return of spontaneous circulation (ROSC)
    • Reteplase
      • 20-U IV bolus
    • Tenecteplase
      • 0.5-mg/kg IV bolus (max 50mg)
  • In patients with massive and submassive PE:
    • Alteplase (FDA-approved)
      • 10-mg IV bolus
      • Followed by 90 mg IV infusion over 2 hrs.
    • Reteplase
      • 10-U IV bolus
      • Followed in 30 mins by another 10-U IV bolus.
    • Tenecteplase
      • 0.5-mg/kg IV bolus (max 50mg)

ESC Guidelines treatment High-risk pulmonary embolism (DO NOT EDIT)

“

Class I 1. Anticoagulation with unfractionated heparin should be initiated without delay in patients with high-risk PE. (Level of Evidence: A) 2. Systemic hypotension should be corrected to prevent progression of RV failure and death due to PE. (Level of Evidence: C) 3. Vasopressive drugs are recommended for hypotensive patients with PE. (Level of Evidence: C) Class IIa 4. Dobutamine and dopamine may be used in patients with PE, low cardiac output and normal blood pressure. (Level of Evidence: B) Class III 5. Aggressive fluid challenge is not recommended. (Level of Evidence: B) Class I 6. Oxygen should be administered in patients with hypoxaemia.(Level of Evidence: C) 7. Thrombolytic therapy should be used in patients with high-risk PE presenting with cardiogenic shock and/or persistent arterial hypotension.(Level of Evidence: A) 8. Surgical pulmonary embolectomy is a recommended therapeutic alternative in patients with high-risk PE in whom thrombolysis is absolutely contraindicated or has failed.(Level of Evidence: C) Class IIb 9.Catheter embolectomy or fragmentation of proximal pulmonary arterial clots may be considered as an alternative to surgical treatment in high-risk patients when thrombolysis is absolutely contraindicated or has failed. (Level of Evidence: C)

”

ESC Guidelines treatment Non-high-risk pulmonary embolism (DO NOT EDIT)

“

Class I 1. Anticoagulation should be initiated without delay in patients with high or intermediate clinical probability of PE while diagnostic workup is still ongoing. (Level of Evidence: C) 2. Use of LMWH or fondaparinux is the recommended form of initial treatment for most patients with non-high-risk PE. (Level of Evidence: A) 3. In patients at high risk of bleeding and in those with severe renal dysfunction, unfractionated heparin with an aPTT target range of 1.5–2.5 times normal is a recommended form of initial treatment. (Level of Evidence: C) 4. Initial treatment with unfractionated heparin, LMWH or fondaparinux should be continued for at least 5 days and (Level of Evidence: A) may be replaced by vitamin K antagonists only after achieving target INR levels for at least 2 consecutive days (Level of Evidence: C) Class IIb 5. Routine use of thrombolysis in non–high-risk PE patients is not recommended, but it may be considered in selected patients with intermediate-risk PE (Level of Evidence: B) Class III 6. Thrombolytic therapy should be not used in patients with low-risk PE (Level of Evidence: B)

”

ESC Guidelines Recommendations Long-term treatment (DO NOT EDIT)

“

Class I 1. For patients with PE secondary to a transient (reversible) risk factor, treatment with a VKA is recommended for 3 months.(Level of Evidence: A) 2. For patients with unprovoked PE, treatment with a VKA is recommended for at least 3 months. (Level of Evidence: A) 3. For patients with a second episode of unprovoked PE, long-term treatment is recommended. (Level of Evidence: A) 4. In patients who receive long-term anticoagulant treatment, the risk/benefit ratio of continuing such treatment should be reassessed at regular intervals. (Level of Evidence: C) 5. In patients with PE, the dose of VKA should be adjusted to maintain a target INR of 2.5 (range 2.0–3.0) regardless of treatment duration. (Level of Evidence: A) Class IIb 6. Patients with a first episode of unprovoked PE and low risk of bleeding, and in whom stable anticoagulation can be achieved, may be considered for long-term oral anticoagulation. (Level of Evidence: B) Class IIa 7. For patients with PE and cancer, LMWH should be considered for the first 3–6 months (Level of Evidence: B) after this period, anticoagulant therapy with VKA or LMWH should be continued indefinitely or until the cancer is considered cured. (Class I,Level of Evidence: C)

”

Guidelines Resources

• Guidelines on the diagnosis and management of acute pulmonary embolism.