Submassive Pulmonary Embolism

Pulmonary embolism with normal systemic blood pressure (systolic 90 mmHg or more) but right ventricular dysfunction on echocardiography or CT, myocardial injury (raised troponin), or both. Also called intermediate risk pulmonary embolism: intermediate high when both are present, intermediate low when one or neither is present.

• It makes up about 20 to 30% of acute pulmonary embolism. With anticoagulation alone, about 5% of intermediate high risk patients die or decompensate within 7 days, and 3-month mortality is about 3 to 10%.
• Mechanism: clot burden raises pulmonary vascular resistance and right ventricular wall tension, with ischaemia of the right ventricle and falling left ventricular filling; compensation may fail suddenly.
• Late consequences: chronic thromboembolic pulmonary hypertension in about 2 to 4%, and persistent dyspnoea or reduced exercise capacity in a third to a half.

• Dyspnoea, pleuritic pain, tachycardia, tachypnoea, hypoxaemia, syncope or presyncope, and raised jugular venous pressure. Blood pressure is normal, though the pulse pressure may narrow and lactate may rise.
• Signs of right ventricular strain: loud pulmonary second sound, right ventricular heave, tricuspid regurgitation murmur.
• Differential diagnosis: pneumonia, myocardial infarction, myocarditis, acute heart failure, pericarditis, aortic dissection, pneumothorax, pulmonary hypertension, and COPD or asthma exacerbation.
• Complications: haemodynamic collapse (about 5% in the first week), arrhythmia, pulmonary infarction, recurrent embolism, bleeding on treatment, and chronic thromboembolic pulmonary hypertension.

• CT pulmonary angiography confirms the embolus and shows right ventricular enlargement (right to left ventricle diameter ratio greater than 1.0), septal bowing, contrast reflux into the inferior vena cava and hepatic veins.
• Echocardiography: right ventricular dilatation, septal flattening, McConnell sign, tricuspid annular plane systolic excursion less than 16 mm, tricuspid regurgitant velocity greater than 2.8 m/s, thrombus in transit.
• Troponin I or T (raised in about 30 to 50%), BNP greater than 100 pg/mL or NT-proBNP greater than 600 pg/mL, lactate (greater than 2 mmol/L signals poor outcome), ECG (right bundle branch block, T inversion in V1 to V4, S1Q3T3), arterial blood gas, creatinine, full blood count, coagulation and pregnancy test.
• Look for the source with compression ultrasonography of the legs; thrombus burden in the proximal veins raises risk.

• Admit to a monitored bed for at least 48 to 72 hours with continuous ECG and SpO2, hourly blood pressure and early repeat lactate; escalate to critical care for any fall in blood pressure.
• Oxygen to keep SpO2 94 to 98% (88 to 92% in COPD with carbon dioxide retention). Fluid no more than 500 mL, avoided if the right ventricle is distended.
• Parenteral anticoagulation first (24 to 72 hours), since it can be reversed or escalated:
  • Unfractionated heparin 80 units/kg IV bolus then 18 units/kg/h, aPTT 1.5 to 2.5 times control, or
  • Enoxaparin 1 mg/kg SC every 12 hours (once daily if creatinine clearance is less than 30 mL/min), or fondaparinux 5 mg (under 50 kg), 7.5 mg (50 to 100 kg), 10 mg (over 100 kg) SC daily (contraindicated when creatinine clearance is less than 30 mL/min).
  • 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 dabigatran 150 mg twice daily or edoxaban 60 mg daily after the parenteral phase; or warfarin to INR 2.0 to 3.0 with at least 5 days of overlap.
• Routine thrombolysis is not recommended. In intermediate high risk disease it lowers death or decompensation (about 5% to about 2.5%) but raises major extracranial bleeding (about 1% to about 6%) and haemorrhagic stroke (about 0.2% to about 2%), with the highest bleeding risk in patients over 75.
• Rescue reperfusion for haemodynamic decompensation (systolic pressure less than 90 mmHg for 15 minutes, a fall of 40 mmHg or more, syncope, vasopressor need, or rising lactate):
  • Alteplase 100 mg IV over 2 hours (or 0.6 mg/kg over 15 minutes, maximum 50 mg, if arrest is imminent); streptokinase 250,000 units over 30 minutes then 100,000 units/h for 12 to 24 hours (or 1.5 million units over 2 hours).
  • Catheter directed therapy when thrombolysis is contraindicated or bleeding risk is high: ultrasound assisted alteplase 1 mg/h per catheter for 5 to 6 hours (total about 10 to 24 mg), or mechanical thrombectomy (evidence is limited).
  • Surgical embolectomy or venoarterial ECMO for failed or contraindicated reperfusion.
• Selected patients (young, low bleeding risk, large clot burden, deteriorating despite anticoagulation): consider half dose alteplase 50 mg over 2 hours (evidence is limited).
• Duration of anticoagulation:
  • Provoked by a major transient factor: 3 months.
  • Unprovoked or persistent risk factor: 3 to 6 months then extended therapy with review; 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, for at least 6 months.
  • Antiphospholipid syndrome: warfarin to INR 2.0 to 3.0; avoid direct oral anticoagulants.
• Supportive care: noradrenaline 0.2 to 1 microgram/kg/min for hypotension; dobutamine 2 to 20 micrograms/kg/min for low output; avoid intubation where possible; early mobilisation once stable.
• Inferior vena cava filter only for proximal thrombosis with an absolute contraindication to anticoagulation or recurrence despite therapeutic anticoagulation.
• Special groups:
  • 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 decompensation.
  • Renal impairment: unfractionated heparin or warfarin.
  • Rifampicin or ritonavir boosted antiretrovirals: avoid direct oral anticoagulants.
  • Elderly: reduce direct oral anticoagulant doses by renal function; thrombolysis carries higher bleeding risk.
• Red flags: falling blood pressure, rising lactate, syncope, new arrhythmia, rising troponin, increasing oxygen requirement.
• Follow up: review at 3 months with symptoms, echocardiography if dyspnoea persists, and a ventilation and perfusion scan to look for chronic thromboembolic disease; review the need for extended anticoagulation yearly.