Pulmonary Embolism

Blockage of a pulmonary artery or its branches due to embolised clot, leading to RV dysfunction and impaired gas exchange. Significance ranges from trivial to life-threatening depending on the size of the occlusion and the cardiorespiratory reserve.

VTE is an umbrella term encompassing both DVT and PE, and is used as there is substantial overlap in both pathologies. This distinction is not made here; this section covers PE whilst DVT is covered in detail under Deep Vein Thrombosis.

PE is classified by degree of haemodynamic impairment into:

Massive
PE with hypotension (SBP <90mmHg). Indication for clot destruction via thrombolysis or embolectomy. Anticoagulation should be commenced once thrombolysis completed.
Submassive
PE with evidence of RV dysfunction ECG, echo). Clot destruction controversial - low-dose thrombolysis may be more appropriate; anticoagulation is indicated.
Mild
PE without haemodynamic instability or RV dysfunction. No indication for clot destruction, anticoagulation is indicated.

Subsegmental PEs are also sometimes described, which refer to distal emboli seen on CT. They usually are asymptomatic, have no clinical significance, and do not require intervention.

Epidemiology and Risk Factors

Risk factors for clot formation are given by Vichows triad:

Systemic prothrombotic effects (e.g. Factor V Leiden, OCP use, obesity) predominantly ↑ risk of DVT (and later embolism), pulmonary disease tends to ↑ risk of PE without ↑ DVT risk.

Stasis
Many thrombi occur around venous valves.
- Advanced age
  Risk ↑ after 40.
- Immobilisation
- Obesity
- General anaesthesia
  ~30-50% greater risk compared to spinal/regional technique.
Endothelial Damage
- Central venous access
Hypercoagulable state
- Surgery
  Incidence depends on type of surgery:
  - Thoracic: ~2%
  - Abdominal: ~1%
  - Hip arthroplasty: Up to 30%
  - Knee arthroplasty: Up to 7%
  - Trauma: 2-6%
  - Neurosurgery: Up to 4%
  - Spinal cord injury: 5-9%
- Hereditary
  - AT III deficiency
  - Protein C or S deficiency
  - Factor V leiden
  - Prothrombin gene deficiency
- Pregnancy
  DVT risk is 5× as high post-partum compared with durign pregnancy, and PE risk is 15× as high.
- Malignancy
- Acute illness
  - Trauma
  - Sepsis
- Inflammatory diseases
  - IBD
  - Autoimmune disease
- Previous VTE
- Drugs
  - OCP
    2-5× ↑ relative risk.
  - Chemotherapeutics
  - Smoking
  - Antipsychotics

Risk factors for death from PE:

Age > 70
Congestive heart failure
COAD
ASA score
Hypotension and tachypnoea on diagnosis

Pathophysiology

Key processes are:

Clot formation and embolisation
PE predominantly arise from DVT in the lower limbs, pelvic veins, or IVC. DVT can then:
- Propagate proximally
  PE will occur in ~50% of patients with proximal DVT. Below knee DVT rarely causes clinicially significant PE.
- Break off entirely
  ~20% of patients with PE have no identified DVT.
Impaired pulmonary gas exchange:
- ↑ alveolar dead space
  Non-perfused alveoli distal to clot.
- Over-perfusion of non-clotted lung
  May cause shunt via a variety of mechanisms:
  - Oedema
  - Pulmonary haemorrhage
    Pulmonary infarction does not usually occur due to ongoing perfusion from bronchial circulation.
  - Loss of surfactant
  - Vasoactive peptide secretion
Acute RV dysfunction
- ↑ PVR
  Pulmonary arterial obstruction leads to ↑ PVR and elevated RV afterload. May be exacerbated by low mixed venous PO₂ .
- ↑ Right-sided pressures
  ↑ in RAP may open a PFO and lead to intracardiac right-to-left shunting and risk of systemic embolism.

Clinical Manifestations

Clinical features depend on:

Clot location
Clot burden
Severity of disease relating to underlying CVS reserve

Features are few and generally non-specific, but may be:

Due to pulmonary infarction
- Haemoptysis
- Pleuritic chest pain
- Pleural rub
Due to pulmonary hypertension
- RV pressure overload
  - ↑ RAP
    May be seen as elevated JVP.
  - ↑ PVR
  - ↓ CO
  - ↑ SVR
- Loud P₂
Due to obstructive shock:
- Cardiac arrest
- Shock Index > 1 is strongly associated with in hospital mortality
- Tachycardia
  May be isolated finding. Tachypnoea
- Hypotension

Diagnostic Approach and DDx

PE should always be considered in patients with:

Sudden onset syncope
Hypotension
Extreme hypoxia
EMD
Cardiac arrest

Assessing a patient who may have PE should:

Commence with careful evaluation of history, risk factors, and physical exam
Use a validated clinical prediction score to stratify need for further investigations
- Wells Score
- Geneva score

Other differentials include:

B
- Pneumonia
- PTHx
- Rib fractures
C
- Acute coronary syndrome
- Aortic dissection
- APO
Trauma
- Fat embolism
Obstetric
- Amniotic fluid embolism

Investigations

Can be divided into:

Diagnostic tests
- Echocardiography
- CT
- V/Q scan
Non-diagnostic tests

Bedside:

ABG
Typically demonstrates:
- Hypoxaemia
  May be only abnormality in smaller PEs.
- Respiratory alkalosis
Echocardiography
- Presence of thrombus
  ~26% of severe PE can be seen on TOE, as this provides better visualisation of the MPA and RPA.
- Other disease
- Quantify RV dysfunction
  Findings include:
  - RV/LV end-diastolic diameter ratio > 0.7
  - RV/LV area ratio > 0.66
  - RV end-diastolic diameter > 27mm
  - “McConnel Sign”
    RV free wall hypokinesis with RV apex normo or hyperkinesis.
  - Septal shift
  - TR jet >270cm/sec
  - Pulmonary artery acceleration time <60ms with maximum TR pressure <60mmHg (60/60 sign)
ECG
- No abnormalities
  ~30%.
- Isolated sinus tachycardia
- Atrial arrythmias
  Associated with higher mortality.
- Repolarisation abnormalities
  Present in ~50% of PE patients.
- RBBB and precordial TWI best correlate with severity
- RV strain/cor pulmonale
  Also non-specific, but suggest massive embolism rather than smaller emvoli.
  - S1Q3T3
  - P-pulmonale
  - Incomplete RBBB
  - RAD

The absence of RV dilation in a haemodynamically unstable patient means that PE is an unlikely diagnosis.

Laboratory:

Bloods
- D-Dimer
  - ~97% sensitive
    May be useful in ruling out PE in patients with low to moderate clinical suspicion. Reduces the need for radiological tests.
  - Non-specific
    Does not support diagnosis or indicate severity. Often raised in the critically ill.
- Troponin
  - Elevated in <50% of patients
  - Associated with adverse outcomes
    Death, inotropes.
- BNP/BNP

Imaging:

CXR
- Useful in supporting or ruling-out other causes of hypoxaemia and hypotension
- Required prior to V/Q scan
Lower limb ultrasound
Identify presence of DVT.
CTPA
- Quicker and more available than V/Q scanning, but requires contrast load
- ~85% sensitive
  Varies depending on machine and radiologist.
  - ↑ to ~100% of PEs with haemodynamic instability
  - Commonly identifies subsegmental PE in asymptomatic patients
    Clinical significance is unclear, but do not require anticoagulation.
V/Q scan
- May not be appropriate if existing cardio-pulmonary disease
- Sensitivity ↑ with modern SPECT devices
  ~1% now non-diagnostic.
- More sensitive than CTPA for peripheral emboli

Other:

Respiratory Function Tests
- Physiological dead space:
  - Almost always ↑ in the case of PE
    Formal measurement is:
    - 100% sensitive
    - 89% specific
  - Requires an intubated/ventilated patient
  - Not easy to perform in practice
  - Suggested by
    - Acute reduction in ETCO₂
    - Delay in reaching alveolar plateau on ETCO₂ waveform

Management

Risk stratification
To determine need for clot destruction via:
- IV thrombolysis
- Interventional radiology
  - Clot retrieval
  - Catheter-directed thrombolysis
- Open thrombectomy
Haemodynamic support
Therapeutic anticoagulation

Resuscitation:

B
- Supplemental oxygen
C
- Haemodynamic support
  - RV support
  - ECMO

Specific therapy:

Therapeutic anticoagulation is covered in detail under Anticoagulation.

Pharmacological
- IV thrombolysis
  - Most common tool
  - Dramatic improvement in haemodynamic state in 90% of patients following administration
    - ~50% reduction in mortality in massive PE
  - Tempered by significant bleeding in 10% of patients with standard dosing
    - Therapy should be ceased and factor replacement commenced if significant bleeding occurs
- Therapeutic anticoagulation
  Inhibits clot progression, allowing intrinsic fibrinolysis to ↓ clot burden. Anticoagulation:
  - ↓ Mortality and recurrence
    May be reasonable to commence prior to formal diagnosis if bleeding risk is low.
  - Initial anticoagulation should be performed with heparin:
    - UFH
      Preferred in:
      - Renal impairment
      - Following thrombolysis/embolectomy due to reversibility
    - LMWH
      - More predictable dose-response than UFH
      - Faster time to therapeutic anticoagulation
  - Transition to oral anticoagulation when bleeding risk stabilised
    - Warfarin
    - DOAC
Procedural
- Interventional radiology
  - Endovascular embolectomy
  - Catheter-directed thrombolysis
- Open (surgical)
  Overtaken by endovascular techniques due to high (25-50%) perioperative mortality, but may be appropriate in massive PE and:
  - Contraindications to thrombolysis
  - Unavailability of interventional radiology
  - Intracardiac thrombus
Physical

Supportive care:

Disposition:

Preventative:

Marginal and Ineffective Therapies

Complications

Death
- 25-30% of patients with RV failure requiring inotropes
- Up to 13% of perioperative PEs
Recurrence
- ~6% within 6 months
  Despite therapeutic anticoagulation.
- ~8% with 12 months
Chronic Thromboembolic Pulmonary Hypertension
Postthrombotic syndrome

Prognosis

References

Desciak MC, Martin DE. Perioperative pulmonary embolism: diagnosis and anesthetic management. J Clin Anesth. 2011;23:153-165.
Tapson VF. Acute Pulmonary Embolism. N Engl J Med. 2008;358:1037-1052.
Tran HA, Gibbs H, Merriman E, et al. New guidelines from the Thrombosis and Haemostasis Society of Australia and New Zealand for the diagnosis and management of venous thromboembolism. Medical Journal of Australia. 2019;210(5):227-235. doi:10.5694/mja2.50004