What are the guidelines for managing pulmonary embolism?

Guidelines for Management of Pulmonary Embolism

Immediate Risk Stratification and Initial Anticoagulation

All patients with suspected PE should receive immediate anticoagulation without waiting for diagnostic confirmation, unless absolute contraindications exist 1, 2. Risk stratification based on hemodynamic stability is the critical first step that determines treatment intensity 2.

Risk Categories

• High-risk PE: Hemodynamic instability with systolic blood pressure <90 mmHg, need for vasopressors, or shock 2
• Intermediate-risk PE: Hemodynamically stable but with evidence of right ventricular dysfunction or myocardial injury 2, 3
• Low-risk PE: Hemodynamically stable without right ventricular dysfunction 2

Treatment Algorithm by Risk Category

High-Risk PE (Hemodynamically Unstable)

Systemic thrombolytic therapy is the first-line treatment for high-risk PE (Class I, Level B) 1, 2. This represents an upgrade from the 2014 guidelines where rescue thrombolysis was Class IIa 1.

Acute management protocol:

• Initiate unfractionated heparin (UFH) with weight-adjusted bolus immediately (Class I, Level C) 2
• Administer systemic thrombolysis as primary treatment 1, 2
• Consider norepinephrine and/or dobutamine for hemodynamic support (Class IIa, Level C) 2
• If thrombolysis is contraindicated or fails, proceed to surgical pulmonary embolectomy (Class I, Level C) 2
• Percutaneous catheter-directed treatment is an alternative option (Class IIa, Level C) 1, 2
• ECMO may be considered in combination with surgical embolectomy or catheter-directed treatment in refractory circulatory collapse or cardiac arrest (Class IIb) 1

Critical caveat: Do NOT routinely administer systemic thrombolysis in intermediate- or low-risk PE 1.

Intermediate-Risk and Low-Risk PE (Hemodynamically Stable)

For patients eligible for direct oral anticoagulants (DOACs), a NOAC is the recommended form of anticoagulant treatment over vitamin K antagonists (Class I, Level A) 1, 2. The approved NOACs include apixaban, dabigatran, edoxaban, and rivaroxaban 1.

Anticoagulation protocol:

• For parenteral anticoagulation (if needed before NOAC): Low molecular weight heparin (LMWH) or fondaparinux is preferred over UFH (Class I, Level A) 2
• Rivaroxaban and apixaban can be initiated immediately without parenteral bridging 4, 5
• Dabigatran and edoxaban require initial parenteral anticoagulation before transition 2, 5
• If VKA is used instead of NOAC, overlap with parenteral anticoagulation until INR reaches 2.5 (range 2.0-3.0) (Class I, Level A) 1, 2

Clinical advantage: Rivaroxaban therapy significantly reduces duration of hospital stay compared to standard VKA therapy (6 vs. 8 days, p=0.0005) 4.

Risk Assessment Tools for Outpatient Management

Low-risk patients should be assessed for suitability for outpatient management (Grade B) 1. The British Thoracic Society provides specific criteria:

Risk stratification tools (use one):

• PESI class I/II 1
• Simplified PESI (sPESI) score of 0 1
• Hestia criteria 1

Exclusion criteria for outpatient management 1:

• Hemodynamic instability (HR >110 bpm; SBP <100 mmHg; requirement for inotropes/critical care/thrombolysis/embolectomy)
• Oxygen saturations <90% on room air
• Active bleeding or high bleeding risk (recent GI bleed/surgery, previous intracranial bleeding, uncontrolled hypertension)
• Already on full-dose anticoagulation at time of PE
• Severe pain requiring opiates
• Other medical comorbidities requiring admission
• CKD stage 4-5 (eGFR <30 mL/min) or severe liver disease
• Heparin-induced thrombocytopenia within the last year
• Social factors (inability to return home, inadequate home care, lack of telephone communication, compliance concerns)

Important note: RV:LV ratio on CT or RV function on echocardiography is not obligatory for identifying low-risk patients for outpatient management (Grade C) 1. However, if RV dilatation is identified, consider measuring cardiac biomarkers (BNP, NT-proBNP, troponin); elevated biomarkers should prompt inpatient admission 1.

Duration of Anticoagulation

All patients require therapeutic anticoagulation for more than 3 months minimum (Class I) 1, 2.

Duration algorithm:

• Discontinue after 3 months: First PE secondary to a major transient/reversible risk factor 1, 2
• Extended anticoagulation (consider indefinite):
  • No identifiable risk factor for index PE event (Class IIa) 1
  • Persistent risk factor other than antiphospholipid syndrome (Class IIa) 1
  • Minor transient/reversible risk factor (Class IIa) 1
  • Recurrent VTE (at least one previous episode of PE or DVT) not related to major transient/reversible risk factor 1, 2
• Indefinite anticoagulation with VKA (mandatory): Antiphospholipid antibody syndrome (Class I) 1, 2

Dose reduction option: After the first 6 months, a reduced dose of apixaban or rivaroxaban should be considered (Class IIa) 1.

Monitoring: Reassess drug tolerance, adherence, hepatic and renal function, and bleeding risk at regular intervals in patients receiving extended anticoagulation 1.

Special Populations

Contraindications to NOACs

NOACs are contraindicated in 1, 2, 6:

• Severe renal impairment (specific thresholds vary by agent)
• Antiphospholipid antibody syndrome (use VKA indefinitely)
• Pregnancy and lactation (Class III) 1
• Hemodynamically unstable patients requiring thrombolysis or pulmonary embolectomy 6

Pregnancy

• Use therapeutic fixed doses of LMWH based on early pregnancy weight 1, 2
• Do NOT insert spinal/epidural needle within 24 hours of last LMWH dose 1
• Do NOT administer LMWH within 4 hours of epidural catheter removal 1
• Thrombolysis or surgical embolectomy should be considered for pregnant women with high-risk PE (Class IIa) 1
• D-dimer measurement and clinical prediction rules should be considered to rule out PE during pregnancy or post-partum period (Class IIa) 1

Cancer Patients

Edoxaban or rivaroxaban should be considered as an alternative to LMWH, with the exception of patients with gastrointestinal cancer (Class IIa) 1.

Inferior Vena Cava Filters

Do NOT routinely use IVC filters (Class III, Level A) 1, 2. IVC filters should only be considered in acute PE with absolute contraindications to anticoagulation (Class IIa, Level C) 2.

Post-PE Care and Follow-Up

Routine clinical evaluation is mandatory 3-6 months after acute PE (Class I) 1, 2. This represents an upgrade from the 2014 guidelines where this was Class IIb 1.

Integrated care model:

• Implement an integrated model of care after acute PE to ensure optimal transition from hospital to ambulatory care (Class I) 1
• Refer symptomatic patients with mismatched perfusion defects on V/Q scan >3 months after acute PE to a pulmonary hypertension/CTEPH expert center (Class I) 1
• Consider results of echocardiography, natriuretic peptide, and/or cardiopulmonary exercise testing when making referral decisions 1

Multidisciplinary Team Approach

Setup of multidisciplinary teams for management of high-risk and selected cases of intermediate-risk PE should be considered (Class IIa), depending on resources and expertise available in each hospital 1.