Pulmonary Embolism

Evaluation

Risk Stratification

Per the ESC 2019 Guidelines, patients are separated into High, Intermediate-High, Intermediate-Low, or Low risk for early mortality.

High-Risk, or Massive PE

• These patients present with hemodynamic instability, evidence of RV dysfunction, and possibly elevated cardiac enzymes.
• Hemodynamic instability is defined as:
  1. Hypotension (SBP < 90 mmHg for 15 minutes, fall in SBP >40 mmHg from baseline for 15 minutes), vasopressor requirement, or cardiac arrest
  2. Exclusion of sepsis, hypovolemic, new arrhythmia

Intermediate Risk, or Submassive PE

• These patients have evidence of RV dysfunction, may have elevated cardiac enzymes, or an elevated PESI risk (class III-IV or sPESI >= 1)

Low-Risk

• No hemodynamic compromise, normal cardiac enzymes (if tested), and no evidence of RV dysfunction
• low PESI risk class (I or II), sPESI = 0

RV Assessment

Either with echocardiography or CT angiography.

Resuscitation of PE

1. Volume management
2. Early vasopressors (NE) +/- inotropes (dobutamine)
3. Consider thrombolysis
4. Avoid intubation
5. Consider ECMO for refractory cases

Treatment Strategy

Massive PE

• Strongly consider thrombolysis with tPA (make sure to review absolute and relative contraindications to thrombolysis).
• If there are absolute contraindications to lytics, then consider IR clot removal or surgical embolectomy.

Submassive/Intermediate Risk PE

Intermediate-High

• If there are no absolute contraindications to lysis, then consider smaller dose of tPA (0.5 mg/kg up to maximum 50 mg) over 2 hours
• If there are relative contraindications consider 25 mg tPA as a slow infusion
• If there are absolute contraindications then anticoagulation alone is preferred.

Intermediate-Low

Anticoagulation alone.

Low-Risk PE

Anticoagulation alone.

Subsegmental PE

• Contentious area. A 2021 study found that the risk of 90-day recurrent VTE in non-anticoagulated patients with isolated single SSPE was ~2%, and those with multiple is about ~5.7%. Interesting, the 90-day risk of recurrent VTE in patients treated with anticoagulation is approx 3% based on prior studies. Therefore, there might not be a clinically significant risk reduction with full anticoagulation for patients with a single SSPE.
• The 2021 CHEST guidelines recommend surveillence over anticoagulation for those with low risk of recurrent VTE, and anticoagulation over surveillance for those at high risk of recurrent VTE. This only applies if proximal DVT is ruled out (with ultrasonography)

Thrombolysis

• Hold anticoagulation (IV heparin) before and during the infusion. Fully anticoagulate patients with IV UFH afterwards (resume without bolus when aPTT <2x ULN). Then, transition to oral agent once stable for 24-48 hours.
• a consistent finding among studies is that thrombolytic therapy leads to early hemodynamic improvement and, although a mortality benefit may exist, it occurs at a cost of increased major bleeding. Per the ESC 2019 guidelines: Thrombolytic therapy leads to faster improvements in pulmonary obstruction, PAP, and PVR in patients with PE, compared with UFH alone; these improvements are accompanied by a reduction in RV dilation on echocardiography.
• 10% risk of severe bleeding, 1.7% risk of intracranial hemorrhage (SRMA)

Massive PE

• FDA approved regimen: IV tPA (alteplase) 100 mg over 2 hours.
• Consider in more urgent situations (none are shown to be superior)
  • infusion over 15 minutes
  • 20 mg IV bolus then 80 mg IV over 2 hours

Intermediate Risk PE

While not routinely considered, thrombolysis can be considered for patients on anticoagulation who are decompensating or have higher risk of early mortality, anticoagulation treatment.

Some studies (particularly PEITHO) have examined thrombolysis in submassive PE and generally find no balanced benefit from thrombolysis (perhaps improved hemodynamic or pulmonary hypertension status, against increased bleeding risk). The MOPETT study used a particular regimen of tPA 0.5 mg/kg (up to a max of 50 mg) given as a 10 mg bolus followed by the remainder over 2 hours (i.e. reduced dose) for a particular definition of submassive PE ("moderate", with few patients having RV dysfunction); it showed that the risk of pulmonary hypertension was reduced compared to anticoagulation alone.

Cardiac Arrest

• Give a 50 mg IV tPA bolus over 2 minutes, consider also starting a vasopressor early if in PEA arrest (obtain aterial access, use POCUS ECHO!). Follow with another 50 mg IV bolus after 15 minutes in the absence of ROSC.
• once a thrombolytic drug is administered, cardiopulmonary resuscitation should be continued for at least 60–90 min before terminating resuscitation attempts (ESC 2019)

Anticoagulation

• Massive/high risk PE --> IV UFH with bolus dose
• Intermediate or low-risk PE --> LMWH or fondaparinux or OAC (DOAC or VKA with bridging)

Special Populations

• Malignancy: Cancer Associated Thrombosis
• Pregnancy:
• Renal failure: IV UFH, VKA
• Prohibitive bleeding risk which is a contraindication to anticoagulation (active bleeding, surgery, etc).
  • Further exclude DVT
  • Consider IVC filter

References

1. 2019 ESC Guidelines for the diagnosis and management of acute pulmonary embolism developed in collaboration with the European Respiratory Society (ERS) | European Heart Journal | Oxford Academic
2. Submassive & Massive PE - EMCrit Project
3. UptoDate
4. Eight pearls for the crashing patient with massive PE