Definition: A pulmonary embolism (PE) that results in hemodynamic compromise and end-organ hypoperfusion. The physical size of the PE does not differentiate a PE as massive or submassive but rather it is the patients physiologic response to the clot(s).

PE Mortality (Wood 2011)

PE Mortality (Wood 2011)

Epidemiology: (Wood 2011)

  • Incidence of PE: 600,000/year in the US
  • Contributes to death in up to 200,000 patients
  • Mortality
    • Overall: 15-17%
    • HD Stable: < 5%
    • HD Unstable (Massive PE): 52-63%
    • 2/3 of mortality occurs within 1st hour
Severe PE Pathophysiology (Wood 2011)

Severe PE Pathophysiology (Wood 2011)


  • Embolus in the pulmonary arteries causes mechanical obstruction to the right ventricle (RV) leading to RV strain
  • Pulmonary embolus causes neurohormonal mediator release in the pulmonary vasculature contributing to increased pulmonary vascular resistance and increased RV strain
  • Increasing RV strain leads to RV decompensation and failure resulting in decreased RV output
  • The RV and left ventricle (LV) are in series. Failure of one ventricle leads to failure of the other.
  • LV failure results in decreased cardiac output (CO), mean arterial pressure (MAP) and end-organ perfusion
  • Decreased CO and MAP leads to worsening RV function (vicious cycle)


  • Signs
    • Tachypnea
    • Tachycardia
    • Hypotension (may be transient)
    • Hypoxia
    • Increased jugular venous distension (if RV failure)
    • Fever (typically low-grade)
    • Lower extremity pain and swelling may be present if the patient has concomitant DVT
  • Symptoms
    • Shortness of breath/Dyspnea
    • Chest pain
    • Lightheadedness or Syncope
    • Hemoptysis
    • Leg pain (if concomitant DVT)

Differential Diagnosis

The differential diagnosis is broad and involves numerous diseases causing shock:

  • ST-Elevation MI (STEMI)
  • Cardiogenic Shock
  • Tension Pneumothorax
  • Cardiac tamponade
  • Severe asthma or COPD exacerbations
  • Anaphylactic Shock
  • Septic Shock
  • Hemorrhagic Shock (ruptured ectopic, occult trauma)

Basics: ABCs, IV, O2, Cardiac Monitor and 12-lead EKG

Airway, Breathing + Circulation

  • Intubation may be necessary if the patient has significant hypoxia that does not respond to supplemental O2 or has respiratory fatigue
  • This is likely to be a physiologically difficult airway
    • Baseline hypoxia makes the risk of critical desaturation during RSI highly likely
    • Hypotension may be worsened by induction medications and by institution of positive pressure ventilation
    • Patients with shock are often acidemic and this acidosis may worsen during paralysis (lack of ventilation leads to rise in PaCO2)
  • Maximize pre-intubation parameters
    • Add high-flow nasal cannula to non-rebreather (NRB) face mask or non-invasive ventilation (NIV)
    • Address hypotension
      PE Death Spiral

      PE Death Spiral

      • Cautious fluid administration 
        • Fluid boluses can lead to distension of the RV
        • Distension of the RV can lead to compromise of the LV outflow tract leading to worsening hypotension
      • Early use of vasopressors (norepinephrine/epinephrine)
      • Consider using relatively “hemodynamically stable” induction medications (ketamine or etomidate) and reducing the dose of the induction agent
    • Minimize apneic time during which PaCO2 rises

Diagnostic Testing

  • Patients with massive PE may not tolerate advanced diagnostic imaging (CT, V/Q scan) due to their hemodynamic instability
  • Often, the diagnosis is made based on limited information from bedside assessment
EKG Pulmonary HTN Findings (Marchick 2010)

EKG Pulmonary HTN Findings (Marchick 2010)


  • Overall, EKG has low sensitivity for PE. It is helpful in ruling out other causes of shock (i.e. STEMI)
  • Findings of acute pulmonary hypertension frequently seen in acute pulmonary embolism (Marchick 2010
  • Simultaneous T-wave inversions in the anterior and inferior leads are uncommon but have a high specificity for PE (Witting 2012)
  • ECG may demonstrate signs of myocardial ischemia, including ST elevations, which can mimic acute coronary syndrome (Shy 2015)
CXR: Hampton Hump

CXR: Hampton Hump

Chest X-ray

  • Classic X-ray findings
    • Hampton Hump: Dome-shaped, pleural based opacification secondary to pulmonary infarct. Pulmonary infarcts may also look similar to infiltrates (as seen in pnuemonia)
    • Westermark Sign: Focal peripheral hyperlucency secondary to underperfusion of blood vessels (oligemia)
  • Overall, low sensitivity and specificity for pulmonary embolism
  • May be useful in finding or ruling out alternative diagnoses (i.e. pneumonia, pneumothorax)
US Showing Clot in Transit (Goldhaber 2002)

US Showing Clot in Transit (Goldhaber 2002)

Point of Care Ultrasound (POCUS) (Mookadam 2010)

  • Allows for rapid elimination of alternative diagnoses
    • FAST: Intra-abdominal Hemorrhage (occult abdominal trauma, ectopic pregnancy)
    • Lung US: Pulmonary edema (in cardiogenic shock), pneumothorax
  • Supporting Evidence for PE 
    • Cardiac US (Goldhaber 2002)
      • Direct visualization of pulmonary embolism
      • RV dilation and hypokinesis
      • Pulmonary hypertension (Becattini 2010)
      • Akinesia of the RV mid-free wall with normal motion of the apex (McConnell sign) (McConnell 1996)
        Interventricular Septal "Bowing"

        Interventricular Septal “Bowing”

        • Original Study: Sensitivity 77%, Specificity 94%
        • However, can see McConnell sign in RV infarction as well (Casazza 2005)
      • Paradoxical interventricular septal bowing, i.e towards the left ventricle
    • DVT study: presence of DVT in acute shortness of breath increases likelihood of PE as cause
Signs of Right Ventricular Strain (Becattini 2010)

Signs of Right Ventricular Strain (Becattini 2010)

Directed Treatment

  • Heparinization
    • Prevents propagation of the PE(s) allowing the patients intrinsic fibrinolysis system to break down the clot
    • Basis of treatment from small, prospective trial in 1960 (Barritt 1960)
      • Patients with presumed PE based on symptoms + signs (advanced diagnostic imaging not available)
      • Reduction in mortality from 5/19 to 2/16
      • Included patients heterogenous in terms of disease severity (not all with signs of massive PE)
    • Heparin options
      • Unfractionated heparin
        • Bolus: 80 units/kg IV
        • Infusion: 18 units/kg/h IV
        • Advantages: short half-life, can be partially reversed with protamine
      • Low-molecular weight heparin (i.e. enoxaparin, dalteparin)
  • Systemic Thrombolytics
    • Mechanism of action: binds to fibrin and converts tissue plasminogen to plasmin thus promoting fibrinolysis
    • Systemic thrombolytics benefits + harms (Wan 2004)
      • Death: 6.5% absolute reduction (6.2% vs. 12.7%) NNT = 16
      • Recurrent PE: 3.2% absolute reduction
      • Major bleeding: 10% absolute increase with thrombolytics (21.9% vs. 11.9%) NNH = 10
    • Professional Organization Recommendation/Level of Evidence
      • AHA: “Reasonable for patients with massive acute PE.” (Class IIa, Level of Evidence B) (Jaff 2011)
      • Chest: “In patients with acute PE associated with hypotension who do not have a high bleeding risk, we suggest systemically administered thrombolytic therapy over no such therapy (Grade 2C) (Kearon 2012)
      • ACEP: “Administer thrombolytic therapy in hemodynamically unstable patients with confirmed PE for whom the benefits of treatment outweigh the risks of life-threatening bleeding complications (Level B recommendation) (Fesmire 2011)
    • Dose: Alteplase 100 mg IV over 2 hours (Kearon 2012). Can also consider giving bolus dose thrombolytics in patients with suspected or confirmed PE who have cardiac arrest.
    • Hold heparin during infusion of alteplase
  • Alternative Options
    • Catheter directed thrombolytics (Piazza 2015)
      • Intravascular catheter is placed into the pulmonary artery via either the femoral or internal jugular vein to the location of the clot
      • Fibrinolytic therapy is delivered directly to the clot
      • Allows for lower dose of fibrinolytic medication to be utilized and may reduce the risk of major bleeding and intracranial hemorrhage
    • Surgical thrombectomy

Take Home Points

  • Massive PE is defined as any PE that results in hemodynamic instability.
  • Patients with massive PE will often be too unstable for advanced diagnostic imaging (i.e. CT scan) requiring bedside diagnosis with history, physical examination and POC US
  • Systemic administration of a fibrinolytic drug is a potentially life-saving therapeutic intervention with an NNT for death of 16. However, it comes with the significant risk of intracranial hemorrhage and major bleeding (NNH = 10)



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