Hemodynamically Unstable Pulmonary Embolism

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)

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 1^st hour

Severe PE Pathophysiology (Wood 2011)

Pathophysiology:

• 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)

Presentation

• 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

    • 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

• 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

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)

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”

      • 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)

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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References:

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Becattini C et al. Right ventricular dysfunction in patients with pulmonary embolism. Intern Emerg Med 2010; 5: 453-5. PMID: 20665963

Casazza F et al. Regional right ventricular dysfunction in acute pulmonary embolism and right ventricular infarction. Eur J Echo 2005; 6: 11-4. PMID: 15664548

Dong BR et al. Thrombolytic therapy for pulmonary embolism (review).  Coch Data Syst Rev 2009; 3: 1-53. PMID: 19588357

Fesmire FM et al.  Critical issues in the evaluation and management of adult patients presenting to the emergency department with suspected pulmonary embolism.  Ann of Emerg Med 2011; 57: 628-52. PMID: 21621092

Goldhaber SZ.  Echocardiography in the management of pulmonary embolism.  Ann Intern Med 2002; 136: 691-700. PMID: 11992305

Jaff MR et al. Management of massive and submassive pulmonary embolism, iliofemoral deep vein thrombosis, and chronic thromboembolic pulmonary hypertension: a scientific statement from the AHA.  Circulation 2011; 123: 1788-1830. PMID: 21422387

Kearon C et al.  Antithrombotic therapy for VTE disease. Chest 2012; 141: e419S-4s. PMID: 22315268

Marchick MR et al. 12-Lead ECG findings of pulmonary hypertension occur more frequently in emergency department patients with pulmonary embolism than in patients without pulmonary embolism. Ann Emerg Med 2010; 55; 331-335. PMID: 19766353

McConnell MV et al. Regional right ventricular dysfunction detected by echocardiography in acute pulmonary embolism. Am J Cardiol 1996; 78: 469-73. PMID: 8752195

Mookadam F et al. Critical appraisal on the utility of echocardiography in the management of acute pulmonary embolism.  Cardiol Rev 2010; 18: 29-37. PMID: 20010336

Piazza G et al. A prospective, single-arm, multi center trial of ultrasound-facilitated, catheter-directed, low-dose fibrinolysis for acute massive and submissive pulmonary embolism – the SEATTLE II study. JACC 2015; 8(10): 1382-93. PMID: 26315743

Shy B et al. Bedside ultrasound to evaluate pulmonary embolism masquerading as ST elevation myocardial infarction (STEMI). J Emerge Med 2015; 49(5): 703-4. PMID: 26164559

Wan S et al. Thrombolysis compared with heparin for the initial treatment of pulmonary embolism: a meta-analysis of the randomized controlled trials.  Circulation 2004; 110: 744-9.PMID: 15262836

Witting MD et al. Simultaneous T-wave inversions in anterior and inferior leads: an uncommon sign of pulmonary embolism. J Emerg Med 2012; 43(2): 228-35. PMID: 22142671

Wood KE. Major Pulmonary Embolism. Crit Care Clin 2011; 27: 885-906. PMID: 22082519