Massive Pulmonary Embolism

Pulmonary embolism with haemodynamic compromise: sustained systolic blood pressure less than 90 mmHg (or a fall of 40 mmHg or more) for at least 15 minutes, vasopressor need, shock or cardiac arrest, not caused by arrhythmia, sepsis or hypovolaemia. Also called high risk pulmonary embolism.

• It makes up about 5% of pulmonary embolism, and short term mortality is about 25 to 50%, rising to 60 to 90% with cardiac arrest. Most deaths occur in the first hours.
• Mechanism: obstruction of more than half of the pulmonary vascular bed, or a smaller obstruction in a patient with limited cardiopulmonary reserve, causes acute right ventricular failure with falling left ventricular filling, hypotension and coronary hypoperfusion, creating a spiral of right ventricular ischaemia.
• Common precipitants: major surgery, trauma, immobility, cancer, pregnancy and the puerperium, and a large residual deep vein thrombosis.

• Sudden dyspnoea, syncope, chest pain, hypotension, tachycardia, cyanosis, raised jugular venous pressure, cool peripheries, oliguria and altered consciousness. Cardiac arrest with pulseless electrical activity is typical.
• Signs of right ventricular failure: right ventricular heave, loud pulmonary second sound, tricuspid regurgitation murmur, hepatic congestion.
• Differential diagnosis: tension pneumothorax, cardiac tamponade, acute myocardial infarction with cardiogenic shock, aortic dissection, massive haemorrhage, septic shock, anaphylaxis, and acute severe asthma.
• Complications: cardiac arrest, multi organ failure, acute kidney injury, bleeding from thrombolysis (major bleeding about 10 to 20%, intracranial haemorrhage about 2 to 3%), recurrent embolism, and chronic thromboembolic pulmonary hypertension in survivors.

• Do not delay treatment for confirmation in a collapsing patient with high clinical probability.
• Bedside echocardiography: dilated, hypokinetic right ventricle with septal flattening, McConnell sign, tricuspid regurgitation, plethoric inferior vena cava, and thrombus in the right heart or pulmonary artery. A normal right ventricle excludes massive pulmonary embolism as the cause of shock.
• CT pulmonary angiography once stable enough to travel; compression ultrasonography of the legs if CT is not possible.
• Blood tests: troponin, BNP, lactate, arterial blood gas, creatinine, full blood count, coagulation, group and crossmatch, pregnancy test. ECG: right bundle branch block, T inversion in V1 to V4, sinus tachycardia, S1Q3T3.

• Resuscitation:
  • Manage in resuscitation or critical care. Give oxygen to keep SpO2 94 to 98%. Avoid intubation unless essential (positive pressure ventilation and induction drugs can precipitate arrest); if needed, use ketamine, low tidal volumes and minimal positive end expiratory pressure.
  • Fluid: no more than 500 mL (excess volume worsens right ventricular distension).
  • Noradrenaline 0.2 to 1 microgram/kg/min to restore perfusion pressure; add dobutamine 2 to 20 micrograms/kg/min for low output. Inhaled nitric oxide or epoprostenol are options in refractory right ventricular failure (evidence is limited).
• Anticoagulation at once: unfractionated heparin 80 units/kg IV bolus then 18 units/kg/h, aPTT 1.5 to 2.5 times control (use unfractionated heparin because it can be stopped and reversed with protamine 1 mg per 100 units given in the previous 2 to 3 hours).
• Systemic thrombolysis is the first line reperfusion treatment for shock:
  • Alteplase 100 mg IV over 2 hours; in cardiac arrest or imminent arrest give alteplase 50 mg IV bolus over 1 to 2 minutes, repeated once after 15 minutes if there is no return of circulation, and continue resuscitation for 60 to 90 minutes.
  • Streptokinase 250,000 units IV over 30 minutes then 100,000 units/h for 12 to 24 hours (or 1.5 million units over 2 hours), or urokinase 4400 units/kg IV over 10 minutes then 4400 units/kg/h for 12 to 24 hours, when alteplase is unavailable.
  • Continue heparin during alteplase; hold it during streptokinase and urokinase and restart without a bolus when aPTT is less than 2 times control.
  • Absolute contraindications: previous haemorrhagic stroke, ischaemic stroke within 6 months, central nervous system neoplasm, major trauma, surgery or head injury within 3 weeks, bleeding diathesis, active bleeding. In massive pulmonary embolism all contraindications are relative, since the alternative is death.
  • Relative contraindications: transient ischaemic attack within 6 months, oral anticoagulation, pregnancy or the first postpartum week, non-compressible punctures, traumatic resuscitation, systolic pressure greater than 180 mmHg, advanced liver disease, infective endocarditis, active peptic ulcer.
• When thrombolysis is contraindicated, has failed (persistent shock after 60 minutes) or the patient is in arrest from known embolism:
  • Surgical pulmonary embolectomy on cardiopulmonary bypass, with removal of right heart thrombus and closure of a patent foramen ovale (perioperative mortality about 6 to 30%, lower when done before arrest).
  • Catheter directed treatment: ultrasound assisted alteplase 1 mg/h per catheter for 5 to 6 hours, or mechanical or aspiration thrombectomy.
  • Venoarterial ECMO as a bridge to embolectomy, thrombolysis or recovery.
• After stabilisation:
  • Parenteral anticoagulation for 24 to 72 hours (enoxaparin 1 mg/kg SC twice daily, or unfractionated heparin), then rivaroxaban 15 mg twice daily with food for 21 days then 20 mg daily, or apixaban 10 mg twice daily for 7 days then 5 mg twice daily, or warfarin to INR 2.0 to 3.0 with at least 5 days of overlap.
  • At least 3 to 6 months of treatment; extended therapy for unprovoked disease (after 6 months reduce to apixaban 2.5 mg twice daily or rivaroxaban 10 mg daily); cancer: apixaban 10 mg twice daily for 7 days then 5 mg twice daily, or enoxaparin 1 mg/kg twice daily; antiphospholipid syndrome: warfarin only.
  • Inferior vena cava filter (retrievable) for proximal thrombosis with an absolute contraindication to anticoagulation, or recurrence on therapeutic anticoagulation.
• Bleeding after thrombolysis: stop heparin, give tranexamic acid 1 g IV over 10 minutes (evidence is limited), cryoprecipitate 10 units if fibrinogen is less than 1.5 g/L, and protamine for heparin effect; urgent CT head if neurological change.
• Special groups:
  • Pregnancy: thrombolysis is acceptable for life threatening embolism (risk of maternal haemorrhage about 8%); surgical embolectomy or catheter directed treatment is an alternative; continue enoxaparin 1 mg/kg twice daily through pregnancy and for at least 6 weeks postpartum; avoid warfarin and direct oral anticoagulants.
  • Cancer and recent surgery: weigh bleeding risk; surgical embolectomy or catheter directed treatment is preferred when bleeding risk is high.
  • Renal impairment: unfractionated heparin; avoid fondaparinux and reduce direct oral anticoagulants.
  • Elderly: higher bleeding risk; do not withhold thrombolysis when shock is present.
  • Rifampicin and ritonavir boosted antiretrovirals: avoid direct oral anticoagulants.
• Red flags: systolic pressure less than 90 mmHg, syncope, lactate rise, arrest, thrombus in transit.
• Follow up: review at 1 week and 3 months with echocardiography; ventilation and perfusion scanning at 3 months for persistent dyspnoea; assess for chronic thromboembolic pulmonary hypertension; decide duration of anticoagulation and investigate for cancer or thrombophilia in unprovoked events.