What is the treatment for pulmonary embolism?

Treatment of Pulmonary Embolism

For patients with pulmonary embolism who are eligible for oral anticoagulation, a non-vitamin K antagonist oral anticoagulant (NOAC) such as apixaban, rivaroxaban, dabigatran, or edoxaban is the recommended first-line anticoagulant treatment. 1

Risk Stratification Determines Treatment Intensity

Treatment approach must be guided by immediate hemodynamic assessment 2, 3:

• High-risk PE: Presence of shock or sustained hypotension (systolic BP <90 mmHg for ≥15 minutes or requiring vasopressor support) 2, 3
• Intermediate-risk PE: Hemodynamically stable but with evidence of right ventricular dysfunction on imaging or elevated cardiac biomarkers 2, 3
• Low-risk PE: Hemodynamically stable without right ventricular dysfunction 2, 3

High-Risk PE: Immediate Reperfusion Required

For patients presenting with hemodynamic instability, mortality risk is immediate and aggressive intervention is mandatory:

• Systemic thrombolytic therapy is the primary treatment and should be administered immediately unless absolute contraindications exist 1, 3
• Initiate unfractionated heparin (UFH) with weight-adjusted bolus (80 U/kg or 5,000-10,000 units) followed by continuous infusion (18 U/kg/h) without delay, targeting aPTT 1.5-2.5 times control 2, 3
• Administer supplemental oxygen to correct hypoxemia (target SaO2 ≥90%) 4, 2
• Use vasopressors (norepinephrine and/or dobutamine) to correct hypotension and support right ventricular function 1, 2
• Avoid aggressive fluid challenges—this worsens right ventricular failure 4, 3
• If thrombolysis is contraindicated or fails, surgical pulmonary embolectomy or catheter-directed treatment should be performed 1, 3
• ECMO may be considered in combination with surgical embolectomy or catheter-directed treatment for refractory circulatory collapse or cardiac arrest 1

Intermediate-Risk and Low-Risk PE: Anticoagulation-Based Strategy

For hemodynamically stable patients, anticoagulation is the cornerstone of treatment:

Initial Parenteral Anticoagulation

• Prefer low molecular weight heparin (LMWH) or fondaparinux over unfractionated heparin for initial parenteral anticoagulation 2, 3
• Do not routinely administer systemic thrombolysis as primary treatment 3
• Rescue thrombolytic therapy is now a Class I recommendation if hemodynamic deterioration occurs despite anticoagulation 1
• Surgical embolectomy or catheter-directed treatment should be considered as alternatives to rescue thrombolysis if deterioration occurs 1

Transition to Oral Anticoagulation

When initiating oral anticoagulation, NOACs (apixaban, rivaroxaban, dabigatran, or edoxaban) are preferred over warfarin 1, 3:

• Apixaban is FDA-approved for treatment of PE 5
• Rivaroxaban is FDA-approved for treatment of PE 6
• These agents offer predictable anticoagulant response without routine monitoring requirements 7

Critical Contraindications to NOACs

Do not use NOACs in the following situations 1, 2, 3:

• Severe renal impairment (CrCl <15-30 mL/min depending on agent) 2, 3, 6
• Pregnancy or lactation 1, 3
• Antiphospholipid antibody syndrome—use vitamin K antagonist (VKA) indefinitely instead 1, 3

For these patients, use LMWH bridged to warfarin (target INR 2-3) 2, 3

Duration of Anticoagulation

The bleeding risk threshold for decision-making is based on 3% per year major bleeding risk with warfarin 8:

• Minimum 3 months of therapeutic anticoagulation for all patients 3, 8
• Discontinue after 3 months: First PE with major transient/reversible risk factor (e.g., surgery, trauma, immobilization) 3, 8
• Extended anticoagulation should be considered for:
  • Unprovoked PE (no identifiable risk factor) 1
  • Persistent risk factors other than antiphospholipid antibody syndrome 1
  • Minor transient/reversible risk factors 1
  • Recurrent VTE not related to major transient risk factor 3
• Reduced-dose NOAC after initial 6 months: Apixaban 2.5 mg twice daily or rivaroxaban 10 mg once daily should be considered for extended therapy 1

Special Populations

Cancer-Associated PE

• Edoxaban or rivaroxaban should be considered as alternatives to LMWH 1
• Exception: Avoid NOACs in gastrointestinal cancer due to increased bleeding risk 1

Pregnancy and Postpartum

• Use therapeutic fixed doses of LMWH based on early pregnancy weight 3
• NOACs are absolutely contraindicated during pregnancy and lactation 1, 3
• Thrombolysis or surgical embolectomy should be considered for pregnant women with high-risk PE 1

Management of Hypoxemia

Escalate oxygen delivery sequentially based on response 4:

1. Conventional supplemental oxygen for SaO2 <90% 4
2. High-flow nasal cannula if conventional oxygen insufficient 4
3. Non-invasive ventilation if high-flow oxygen fails 4
4. Invasive mechanical ventilation only for extreme instability—positive pressure ventilation may worsen right ventricular failure 4

If intubation becomes necessary 4:

• Use tidal volumes ~6 mL/kg lean body weight
• Keep end-inspiratory plateau pressure <30 cm H2O
• Apply positive end-expiratory pressure cautiously
• Avoid hypotension-inducing anesthetic agents

Critical Pitfall: Refractory Hypoxemia

Consider right-to-left shunting through patent foramen ovale as a cause of refractory hypoxemia that doesn't respond to escalating oxygen therapy 4

Post-PE Follow-Up and Long-Term Sequelae

Routine clinical evaluation is mandatory 3-6 months after acute PE 1, 3:

• Implement integrated care models to ensure optimal transition from hospital to ambulatory care 1, 3
• Refer symptomatic patients with mismatched perfusion defects on V/Q scan >3 months after acute PE to a pulmonary hypertension/CTEPH expert center, incorporating echocardiography, natriuretic peptide, and/or cardiopulmonary exercise testing results 1
• Further evaluation may be considered for asymptomatic PE survivors at increased risk for chronic thromboembolic pulmonary hypertension (CTEPH) 1

Critical Pitfalls to Avoid

• Do not routinely use inferior vena cava filters—reserve only for absolute contraindications to anticoagulation or PE recurrence despite therapeutic anticoagulation 2, 3
• Do not delay anticoagulation while awaiting diagnostic imaging in high-probability cases 3
• Do not use aggressive fluid challenges in PE patients with right ventricular dysfunction—this worsens hemodynamics 4, 3
• Do not fail to consider rescue thrombolysis in patients with worsening hypoxemia and hemodynamic deterioration despite anticoagulation 4
• Do not delay escalation of oxygen therapy when conventional supplementation is insufficient 4
• Do not overlook the 2019 upgrade of rescue thrombolytic therapy from Class IIa to Class I recommendation for hemodynamic deterioration 1

Multidisciplinary Team Approach

Set-up of multidisciplinary teams for management of high-risk and selected cases of intermediate-risk PE should be considered, depending on resources and expertise available in each hospital 1