Pulmonary embolus

Partial or complete occlusion of the pulmonary arteries

Pathophysiology

• Haemodynamic consequences are determined by the size and location of the embolus, pre-existing cardiopulmonary disease, and severity of ventilation and oxygenation compromise
• Physical obstruction of pulmonary arteries is accompanied by hypoxaemic vasoconstriction and release of potent pulmonary arterial vasoconstrictors, which further increases pulmonary vascular resistance and RV afterload
• Increasing RV afterload causes RV hypokinesis and dilation, tricuspid regurgitation, and ultimately RV failure
• Once RV begins to fail, there is life-threatening reduction in coronary perfusion and downstream cardiac output
• In most patients, pulmonary clots will gradually reabsorb. In some patients, they organise into fibrotic deposits which permanently occlude the pulmonary arteries, leading to chronic pulmonary hypertension and RV dysfunction

Aetiology

• Primary
• Secondary
  • Majority of patients with PE have secondary PE from DVT in lower extremity/pelvis

Clinical presentation

• Spectrum of asymptomatic to fatal
• Classically, sudden onset of symptoms
• Dyspnoea - if severe, indicates lobar or main vessel
• Pleuritic chest pain - pleural irritation due to distal emboli causing pulmonary infarction
  • In central PE, chest pain has a typical angina character, possibly reflecting RV ischaemia
• Presyncope/syncope - can be independent of haemodynamic status
• Haemoptysis - occurs with pulmonary infarction
• Tachypnoea, tachycardia, rales/decreased breath sounds, increased JVP, fever (rare)
• Half of patients will also have symptoms of DVT

Diagnosis

• High index of suspicion required
• Clinical impression has a sensitivity and specificity of 85% and 51% respectively
• Blood tests are non-specific
  • D-dimer <10microg/L * age has good sensitivity
  • Troponin and BNP are recommended for stratification of patients with confirmed PE
• ECG changes are unreliable
  • Similar to all other causes of pulmonary hypertension
  • S1Q3T3 (prominent S wave in lead I, Q wave and inverted T wave in lead III) reflects RV strain, but is seen in less than 20% of diagnosed PEs
• CXR is not sensitive or specific and all signs are rare
  • Generally normal CXR
  • Fleischner sign - enlarged pulmonary artery
  • Hampton hump - peripheral wedge of airspace opacity - lung infarction
  • Westermarck sign - regional oligaemia
  • Knuckle sign - abrupt tapering or cut-off of a pulmonary artery
• CTPA
  • Sensitivity 83% specificity 96%
• Echocardiogram
  • Can diagnose RV dysfunction but not PE
  • Not recommended routinely, but can be used to justify emergency reperfusion treatment for PA
• V/Q scan
  • Primarily used in renal failure and pregnancy
  • Highly sensitive but non-specific

Approach:

• Wells score
  • Unlikely: D-dimer +/- imaging
  • Likely: imaging

Risk stratification

• Low (approx 40% of PEs): normotensive patients without imaging evidence of RV dysfunction or elevated cardiac biomarkers. Mortality rate 1-2%.
• Intermediate (55% of PEs): normotensive patients with either imaging evidence of RV dysfunction or elevated cardiac biomarkers or both. Mortality rate 3-15%.
  • Should try to quantify risk further by looking at RV
• High (5% of all PEs): haemodynamically unstable patients with sustained shock or hypotension <90mmHg or cardiac arrest. In-hospital mortality 15-30%.
• Can also use the PESI score to quantify risk.

Treatment

• Goals
  • Prevent mortality
• Initial supportive therapy (especially for intermediate or high risk patients)
  • Resuscitate, being mindful of already stretched RV
  • If fluid challenge fails, vasopressors will be required (noradrenaline is best because it is less likely to cause tachycardia and exacerbate hypotension)
  • Systemic anticoagulation unless contraindicated - standard duration three months
    • Therapeutic clexane in most cases followed by warfarin/DOAC
  • IVC filter if absolute contraindication to anticoagulation
• Thrombolysis
  • Greatest benefit when done within 48 hours of symptom onset, for high-risk and selected intermediate-risk PE
  • Can be done up to 14 days
  • Systemic thrombolysis
    • Universally recommended for high-risk PE in absence of contraindications
    • 100mg alteplase over 2 hours
    • Demonstrated all-cause (47 vs 15%) and PE-specific (42 vs 8.4%) mortality benefit in high-risk PE
  • Catheter-directed interventions
    • Useful when systemic thrombolysis is contraindicated, but not much data at this stage
    • When available, may be safer for patients who don't have a contraindication to systemic thrombolysis too
    • Controversy over how high to run the heparin infusion while doing catheter-directed interventions - some say use a lower rate like 60-80 APTT
• Surgical thrombectomy
  • Traditionally done for patients with documented central PE and refractory cardiogenic shock despite maximal supportive therapy, and who have absolute contraindications/have failed thrombolytic therapy
  • Best performed through a median sternotomy using a normothermic cardiopulmonary bypass

Special populations

• Asymptomatic subsegmental PE
  • Controversial treatment strategy
  • Favour anticoagulation if:
    • Risk factors for recurrent or progressive VTE
    • Hospitalised or have reduced mobility for another reason
    • Active cancer
    • Low cardiopulmonary reserve
    • Marked symptoms
  • Favour no anticoagulation is high bleeding risk
• Thrombus in transit
  • Floating right heart thrombus
  • Most commonly seen with clots moving towards the pulmonary vasculature from the periphery
  • Mortality rate up to 40%
  • No distinct guidelines
  • Surgery favoured if PFO present
• Pregnancy
  • In one study, no patient with an original Wells score <6 had a PE
  • Questionable utility of D-dimer since physiological levels are higher in pregnancy
  • Adjusted dose LMWH is the favoured treatment
• Cancer
  • First-line therapy should be LMWH for 3-6 months, or as long as the cancer or its treatment continues
• Non-thrombotic PE
  • Fat embolism
    • Usually after long bone fracture or orthopaedic surgery
    • Triad of pulmonary distress, altered GCS, and petechial rash
    • Treat with supportive measures and possibly steroids
  • Amniotic fluid embolism
  • Tumour cell embolisation
  • Septic embolisation
  • Air embolisation
    • Lethal volume 100-500mL
    • Supportive - high-flow oxygen, place patient in left lateral decubitus to prevent RV outflow obstruction by airlock
    • Can attempt aspiration by central catheter

Prognosis

• 10% mortality within 3 months of diagnosis
• Mortality exceeds 60% for those requiring CPR.