Acute Pulmonary Embolism

Obstruction of the pulmonary arteries by thrombus, usually from a deep vein thrombosis of the leg or pelvis (about 70% of patients with pulmonary embolism have detectable deep vein thrombosis). Rarer emboli: fat, air, amniotic fluid, tumour, septic material.

• Incidence is about 60 to 120 per 100,000 per year, rising steeply with age. Short term mortality is about 2 to 10% with treatment (higher with right ventricular dysfunction), and up to about 25 to 30% untreated. It is a leading cause of preventable hospital death.
• Risk factors: major surgery or trauma (especially orthopaedic), immobility, active cancer, pregnancy and the puerperium, oestrogen therapy, previous venous thromboembolism, inherited or acquired thrombophilia, obesity, long haul travel, central venous catheters, heart failure, COPD, nephrotic syndrome, inflammatory bowel disease, HIV and tuberculosis.
• Mechanism: obstruction raises pulmonary vascular resistance and right ventricular afterload, causing right ventricular dilatation, falling left ventricular filling and cardiac output, and ventilation to perfusion mismatch with hypoxaemia. Death is from acute right ventricular failure.
• Severity classes: high risk (sustained hypotension, shock or cardiac arrest), intermediate high (normal blood pressure with both right ventricular dysfunction and raised troponin), intermediate low (one or neither), and low risk.
• About 2 to 4% develop chronic thromboembolic pulmonary hypertension, and many have persistent dyspnoea or reduced exercise capacity.

• Dyspnoea (about 80%), pleuritic chest pain (about 50%), cough, haemoptysis (about 10%), syncope or presyncope (about 10%), and leg swelling. Some patients have only unexplained tachycardia or hypoxia.
• Signs: tachycardia, tachypnoea, low grade fever, oxygen desaturation, raised jugular venous pressure, loud pulmonary second sound, right ventricular heave, calf swelling and tenderness. Hypotension, cyanosis and syncope signal severe disease.
• Differential diagnosis: pneumonia, myocardial infarction, pericarditis, pneumothorax, acute heart failure, asthma or COPD exacerbation, aortic dissection, musculoskeletal chest pain, anxiety and sepsis.
• Complications: right ventricular failure, shock and cardiac arrest, pulmonary infarction, recurrent embolism, chronic thromboembolic pulmonary hypertension, post-embolism syndrome, and bleeding on treatment.

• Estimate clinical probability first (a two level clinical probability score: greater than 4 points is "likely"). With low probability and all of the following, no testing is needed: age less than 50, heart rate less than 100, SpO2 95% or more, no haemoptysis, no oestrogen use, no previous venous thromboembolism, no unilateral leg swelling, no recent surgery or trauma.
• Probability "unlikely": D-dimer with an age adjusted cut off (age in years times 10 micrograms/L for patients over 50, otherwise 500 micrograms/L); a negative result excludes embolism. Probability "likely", or a positive D-dimer: imaging.
• CT pulmonary angiography is the first line test (filling defect in a pulmonary artery). Ventilation and perfusion scanning when CT is contraindicated (severe renal impairment, contrast allergy, pregnancy with a normal chest X-ray). Compression ultrasonography of the legs when CT cannot be done.
• Unstable patient: bedside echocardiography (right ventricular dilatation, right to left ventricle ratio greater than 1, septal flattening, McConnell sign, tricuspid annular plane systolic excursion less than 16 mm, raised pulmonary pressure, thrombus in transit). Start treatment when echocardiography suggests embolism and CT is not possible.
• Risk assessment: troponin, BNP (greater than 100 pg/mL) or NT-proBNP (greater than 600 pg/mL), CT or echocardiographic right ventricular size, lactate, and the simplified pulmonary embolism severity index (one point each for age over 80, cancer, chronic cardiopulmonary disease, heart rate 110 or more, systolic pressure less than 100 mmHg, SpO2 less than 90%; zero means low risk).
• ECG: sinus tachycardia, S1Q3T3, right bundle branch block, T wave inversion in V1 to V4, atrial fibrillation. Chest X-ray: Hampton hump, Westermark sign, atelectasis, effusion; may be normal. Arterial blood gas: hypoxaemia, respiratory alkalosis.
• Also: full blood count, creatinine, liver function, coagulation, pregnancy test, group and save. Thrombophilia testing only when it would change management.

• Immediate care: oxygen to keep SpO2 94 to 98% (88 to 92% in COPD with carbon dioxide retention), analgesia, and cautious fluids (no more than 500 mL, since excess volume distends the failing right ventricle). Start anticoagulation as soon as the diagnosis is likely, before imaging when suspicion is high and bleeding risk is acceptable.
• Initial anticoagulation (choose one):
  • Enoxaparin 1 mg/kg SC every 12 hours (or 1.5 mg/kg once daily); 1 mg/kg once daily when creatinine clearance is less than 30 mL/min.
  • Unfractionated heparin 80 units/kg IV bolus then 18 units/kg/h, aPTT 1.5 to 2.5 times control (preferred with creatinine clearance less than 30 mL/min, high bleeding risk, possible thrombolysis or intervention, and unstable patients).
  • Fondaparinux 5 mg (under 50 kg), 7.5 mg (50 to 100 kg) or 10 mg (over 100 kg) SC once daily; contraindicated when creatinine clearance is less than 30 mL/min.
  • Rivaroxaban 15 mg twice daily with food for 21 days, then 20 mg once daily, or apixaban 10 mg twice daily for 7 days, then 5 mg twice daily, can be started at once without a parenteral lead in.
  • Dabigatran 150 mg twice daily (110 mg twice daily if age 80 or more or taking verapamil) or edoxaban 60 mg once daily (30 mg if creatinine clearance is 15 to 50 mL/min, weight 60 kg or less, or on potent P-glycoprotein inhibitors) after at least 5 days of parenteral treatment.
  • Warfarin to INR 2.0 to 3.0, started on day 1 with at least 5 days of overlap and until INR is 2.0 or more for 24 hours.
• Duration:
  • Provoked by a major transient risk factor (surgery, trauma, immobility): 3 months.
  • Unprovoked or persistent risk factor: at least 3 to 6 months, then extended therapy if bleeding risk is acceptable, with review each year. After 6 months of full dose treatment, reduce to apixaban 2.5 mg twice daily or rivaroxaban 10 mg once daily.
  • Cancer: apixaban 10 mg twice daily for 7 days then 5 mg twice daily, or enoxaparin 1 mg/kg twice daily (or 1.5 mg/kg daily), for at least 6 months and while the cancer is active.
  • Antiphospholipid syndrome: warfarin to INR 2.0 to 3.0 (target higher, 3.0 to 4.0, if recurrence occurs on treatment); avoid direct oral anticoagulants.
• Risk adapted treatment:
  • Low risk (simplified index 0, normal right ventricle and troponin, good home support): early discharge or outpatient treatment with a direct oral anticoagulant.
  • Intermediate risk: admit for 48 to 72 hours of monitoring; use parenteral anticoagulation first; give rescue reperfusion if haemodynamic decompensation develops.
  • High risk (shock): systemic thrombolysis with alteplase 100 mg IV over 2 hours (or 0.6 mg/kg over 15 minutes, maximum 50 mg, when arrest is imminent), 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. Continue unfractionated heparin during alteplase and hold it during streptokinase and urokinase, restarting without a bolus when aPTT is less than 2 times control.
  • Absolute contraindications to thrombolysis: 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 life threatening embolism these become relative.
  • Surgical embolectomy or catheter directed treatment when thrombolysis is contraindicated or has failed; venoarterial ECMO as a bridge in refractory shock or arrest.
• Supportive care for the failing right ventricle: noradrenaline 0.2 to 1 microgram/kg/min for hypotension, dobutamine 2 to 20 micrograms/kg/min for low output, and avoidance of intubation where possible (induction can precipitate arrest; if needed use ketamine, low tidal volumes and minimal positive end expiratory pressure).
• Inferior vena cava filter (retrievable) only for acute proximal thrombosis with an absolute contraindication to anticoagulation, or recurrence despite therapeutic anticoagulation; remove once anticoagulation can start.
• Recurrence on therapeutic anticoagulation: check adherence, dose and drug interactions, exclude cancer, antiphospholipid syndrome and heparin induced thrombocytopenia, then increase enoxaparin by 25% or switch to enoxaparin 1 mg/kg twice daily.
• Drug interactions and special groups:
  • Rifampicin and some antiepileptics lower direct oral anticoagulant levels (avoid; use enoxaparin or warfarin); ritonavir boosted antiretrovirals raise levels (avoid rivaroxaban and apixaban).
  • Pregnancy: enoxaparin 1 mg/kg SC twice daily through pregnancy and for at least 6 weeks postpartum (minimum total 3 months); avoid warfarin and direct oral anticoagulants; thrombolysis only for life threatening disease.
  • Renal impairment: unfractionated heparin or warfarin when creatinine clearance is less than 15 to 30 mL/min.
  • Obesity (weight over 120 kg or BMI over 40): enoxaparin by actual weight or warfarin; direct oral anticoagulant data are limited.
  • Elderly: lower thresholds for dose reduction by renal function; falls risk is not by itself a contraindication.
  • Heparin induced thrombocytopenia: stop heparin; argatroban 2 micrograms/kg/min IV (0.5 to 1 microgram/kg/min in hepatic impairment) or fondaparinux.
• Red flags: systolic pressure less than 90 mmHg, syncope, lactate rise, troponin rise with right ventricular dilatation, thrombus in transit, rising oxygen requirement.
• Follow up: review at 3 months; persistent dyspnoea or exercise limitation needs echocardiography and a ventilation and perfusion scan to look for chronic thromboembolic disease; reassess the need for extended anticoagulation; age appropriate cancer review for unprovoked events.