What is the recommended management for pulmonary embolism?

Management of Pulmonary Embolism

Immediate anticoagulation should be initiated without delay in all patients with suspected PE while diagnostic workup proceeds, with treatment stratified by hemodynamic stability: high-risk PE requires systemic thrombolysis, while intermediate- and low-risk PE are managed with anticoagulation alone, preferably using NOACs over vitamin K antagonists in eligible patients. 1

Risk Stratification

Risk stratification is the critical first step that determines the entire treatment pathway 1, 2:

• High-risk PE: Presence of shock or persistent hypotension (systolic BP <90 mmHg for ≥15 minutes or requiring vasopressor support) 1, 2
• Intermediate-risk PE: Hemodynamically stable but with evidence of right ventricular dysfunction (on echocardiography or CT) and/or myocardial injury (elevated troponin or BNP) 1, 2
• Low-risk PE: Hemodynamically stable without right ventricular dysfunction or myocardial injury 1, 2

High-Risk (Massive) Pulmonary Embolism

Immediate Resuscitation

• Initiate unfractionated heparin (UFH) immediately with weight-adjusted bolus (80 units/kg or 5,000-10,000 units) followed by continuous infusion (18 units/kg/hour, adjusted to maintain aPTT 1.5-2.5 times control) 1, 2
• Administer oxygen to correct hypoxemia 1, 2
• Use vasopressors (norepinephrine and/or dobutamine) to correct hypotension and prevent right ventricular failure 1, 2
• Avoid aggressive fluid challenge as it may worsen right ventricular function 1

Reperfusion Therapy

Systemic thrombolytic therapy is the first-line treatment for high-risk PE and should be administered unless absolutely contraindicated 1, 2. The 2019 ESC guidelines provide the strongest recommendation (Class I, Level B) for this approach 1.

• Alteplase 50 mg IV bolus is recommended if cardiac arrest is imminent 1
• For stable patients after confirmation, use alteplase 100 mg over 90 minutes (accelerated MI regimen) 1
• Thrombolysis may be instituted on clinical grounds alone if cardiac arrest is imminent, even before imaging confirmation 1

Alternative Reperfusion Strategies

When thrombolysis is contraindicated or has failed 1:

• Surgical pulmonary embolectomy is recommended (Class I, Level C) 1
• Percutaneous catheter-directed treatment should be considered (Class IIa, Level C) 1
• ECMO may be considered in combination with surgical or catheter-directed treatment in patients with refractory circulatory collapse or cardiac arrest 1

Common pitfall: Do not use rivaroxaban or other NOACs acutely as an alternative to UFH in hemodynamically unstable PE patients or those who may require thrombolysis 3.

Intermediate-Risk (Submassive) Pulmonary Embolism

Initial Anticoagulation

Low molecular weight heparin (LMWH) or fondaparinux is recommended over UFH for most patients (Class I, Level A) 1, 2. This represents a key difference from high-risk PE management.

• LMWH has equal efficacy and safety to UFH with easier administration 1, 4, 5
• Fixed-dose subcutaneous administration once or twice daily without laboratory monitoring 4, 6
• All available LMWHs (enoxaparin, dalteparin, nadroparin, tinzaparin) appear to have similar efficacy 4, 5

Use UFH instead of LMWH in these specific situations 1, 2:

• Severe renal dysfunction (CrCl <30 mL/min) 1
• High bleeding risk requiring potential rapid reversal 1
• As first-dose bolus in unstable patients 1

Thrombolysis Considerations

Routine use of primary systemic thrombolysis is NOT recommended in intermediate-risk PE (Class III, Level B) 1. However, the evidence shows nuance:

• A 2008 trial of 256 intermediate-risk patients showed thrombolysis reduced the combined endpoint of death or clinical deterioration, though overall mortality was unchanged 1
• Rescue thrombolytic therapy IS recommended if hemodynamic deterioration occurs on anticoagulation (Class I, Level B) 1
• Thrombolysis may be considered in selected intermediate-risk patients without elevated bleeding risk, though this remains controversial 1

Low-Risk Pulmonary Embolism

Anticoagulation Protocol

Initiate anticoagulation without delay in patients with high or intermediate clinical probability while diagnostic workup proceeds 1, 2:

1. Start with LMWH or fondaparinux (preferred over UFH) 1
2. When transitioning to oral anticoagulation, NOACs (apixaban, dabigatran, edoxaban, or rivaroxaban) are recommended in preference to vitamin K antagonists (VKAs) (Class I, Level A) 1, 3

NOAC Contraindications

NOACs are NOT recommended in 1:

• Severe renal impairment (CrCl <30 mL/min for most NOACs; <15 mL/min for rivaroxaban) 1, 3
• Pregnancy and lactation 1
• Antiphospholipid antibody syndrome (especially triple-positive patients have increased thrombotic events with NOACs) 3

VKA Management (When NOACs Contraindicated)

• Overlap parenteral anticoagulation with VKA until INR reaches 2.0-3.0 (target 2.5) for at least 2 consecutive days 1
• Continue parenteral anticoagulation for at least 5 days 1

Duration of Anticoagulation

The 2003 British Thoracic Society guidelines provide specific durations 1:

• 4-6 weeks for temporary/reversible risk factors (Level A) 1
• 3 months for first idiopathic PE (Level A) 1
• At least 6 months for other indications 1
• For cancer-associated PE, at least 6 months of LMWH followed by LMWH or VKA as long as cancer is active 1

Early Discharge and Home Treatment

Carefully selected low-risk PE patients should be considered for early discharge and home treatment (Class IIa, Level A) 1, 2, provided:

• Patient is not unduly breathless 1
• No medical or social contraindications exist 1
• Proper outpatient care and anticoagulant treatment can be provided 1

This approach mirrors successful outpatient DVT management protocols 1, 4, 7.

Inferior Vena Cava Filters

IVC filters should be considered in specific situations only 1:

• Acute PE with absolute contraindications to anticoagulation (Class IIa, Level C) 1
• PE recurrence despite therapeutic anticoagulation (Class IIa, Level C) 1

Routine use of IVC filters is NOT recommended (Class III, Level A) 1. The PREPIC studies showed no mortality benefit and potential long-term complications 1.

Critical Pitfalls to Avoid

1. Do not delay anticoagulation while awaiting imaging in patients with high or intermediate clinical probability 1, 2
2. Do not use thrombolysis routinely in non-high-risk PE 1
3. Do not use aggressive fluid resuscitation in high-risk PE as it worsens right ventricular function 1
4. Do not start oral anticoagulation before VTE is confirmed 1
5. Do not use NOACs in hemodynamically unstable PE requiring potential thrombolysis 3
6. Do not use NOACs in triple-positive antiphospholipid syndrome due to increased thrombotic risk 3