Pulmonary Embolism

Pulmonary embolus (PE) refers to a blockage of the pulmonary artery or one of its branches by various entities that originated elsewhere in the body.  These entities include thrombus, tumor, air, and fat embolus.

A variety of naming systems exist:

Based on timing

1) Acute  PE– patient who develop signs and symptoms immediately after obstruction

2) Subacute PE – Patients present within days to weeks following event.

3) Chronic PE– Chronic PE who slowly develop symptoms of pulmonary hypertension over many years

Based on hemodynamic stability

1) “Massive” PE – PE that causes signs of right heart strain and hemdynamic instability (hypotension with systolic BP < 90,  or a drop in systolic BP > 40 from baseline for > 15 minutes, or hypotension requiring vasopressor or inotropic support.  These patients are more likely to die from obstructive shock (severe right ventricular failure)

2) “Sub-massive” PE – PE that causes right heart strain but does not cause hemodynamic instability

3) “Low-risk” PE – no signs of right heart strain and no hemodynamic instability.

Based on anatomic location

1) Saddle PE – lodges at the bifurcation of the main pulmonary artery.  Associated with a 5% mortality.

2) Lobar, segmental, sub-segmental PEs – at their respective location

The incidence of PE in the United States is estimated to be 1 case per 1000 persons per year, which is about 250,000 incident cases annually.  PE is present in 60-80% of patients with DVT even though more than half of these patients are asymptomatic.   

PE is the third most common cause of death in hospitalized patients, with at least 650,000 cases occurring annually.  

The incidence of PE is higher in African Americans, elderly patients, those with malignancy, pregnant patients.

Pulmonary embolism most commonly originates from a thrombus that forms in the deep veins of the lower extremities and travel to the pulmonary vasculature.  A constellation of risk factors called Virchow’s triad contributes to the formation of thrombus in the lower extremities; these include venous stasis, endothelial injury, and a hypercoagulable state.

Most emboli thought to arise from lower extremity proximal veins (iliac, femoral, and popliteal).   Most develop at sites of decreased flow, such as valve cusps or bifurcations.   

Once a thrombus lodges in the lung, several pathophysiological responses occur, which include pulmonary infarction, abnormal gas exchange, and cardiovascular compromise.

A thorough history should be obtained, with careful questioning for the presence of venous stasis, immobilization, in dwelling lines and catheters, hypercoagulable state, recent surgery in the last 3 months, trauma, pregnancy, malignancy especially lung cancer, oral contraceptive or exogenous estrogen use, prior history of PE, recent travel of 4 hours or more in the past month.

The presentation of PE is variable, and may range from sudden catastrophic hemodynamic collapse to progressively worsening dyspnea.  

The most common symptoms according to the PIOPED II study are: dyspnea (73%), pleuritic chest pain (66%), cough (37%), and hemoptysis (13%).  

The most common signs are: tachypnea (96%) of patients, rales, tachycardia, fever, diaphoresis, S3 or S4 gallop, lower extremity edema, cardiac murmur, and cyanosis.

Patients may present with atypical symptoms, in which the presence of risk factors are key.  Atypical symptoms include seizure, syncope, abdominal pain, fever, productive cough, wheezing, altered mental status, new onset atrial fibrillation, flank pain, or delirium in elderly patients.

Patients with massive PE are in shock, and may have systemic hypotension, poor perfusion of extremities, tachycardia, tachypnea, weak appearing, pale, diaphoretic, and altered mental status.

Physical exam may reveal increased work of breathing and rales on pulmonary exam, tachycardia and murmurs on cardiac exam.  Calf tenderness and swelling will increase the suspicion of presence of DVT that may have precipitated the PE.   

The most common EKG abnormality in PE is sinus tachycardia, along with nonspecific ST-T abnormalities.  The finding of S1Q3T3 is nonspecific and insensitive in the absence of clinical suspicion of PE.  The classic right heart strain findings on EKG are tall, peaked P waves in lead II (P pulmonale), right axis deviation, right bundle branch block, dominant R wave in V1, or atrial fibrillation.   Only 20% of patients with proven PE have any of these classic EKG findings unfortunately.

Diagnosis of PE based on clinical signs are difficult given they are nonspecific.  Patients suspected of having PE along with unexplained dyspnea, tachypnea or chest pain should undergo further diagnostic testing.

Evidence-based literature backs up the use of determining the likelihood of PE before proceeding further with testing.

Initial gestalt for determining PE likelihood may begin with utilizing the PERC rule, which can be applied to patients where the diagnosis of PE is considered, but the patient is deemed low-risk.  A patient who is low risk, who is also < 50 years old, with a pulse < 100 bpm, oxygen saturation > 95%, no hemoptysis, no estrogen use, no history of surgery/trauma within 4 weeks, no prior PE/DVT, and no present signs of DVT can be safely ruled out and does not require further workup.   

If a patient is unable to meet all these criteria,  a patient can further be risk stratified in low, moderate, or high risk groups based on a Wells score (which assigns a score based on clinical signs/symptoms of DVT, heart rate > 100, immobilization or surgery recently, previous PE or DVT, hemoptysis, malignancy with treatment within 6 months, and PE diagnosis is #1 or equally likely diagnosis.

If in the low-risk category, the clinician may proceed with d-dimer blood testing.  D-Dimer is a breakdown product produced by the proteases of fibrin (which are components of thrombus).   A negative d-dimer test (which is high sensitivity) indicates a very low likelihood of DVT or PE, and can reliably exclude PE.  

If a patient has a positive d-dimer, or is in a high risk category for PE, they must undergo further diagnostic imaging.  CT angiography of the chest is the imaging modality of choice for stable patients suspected of PE and is the current standard of care by the American College of Radiology.  If the patient has a contrast allergy, they may undergo a ventilation/perfusion (V/Q) scan. A V/Q scan involves inhaling an aerosolized radionuclide while also receiving an intravenous injection of radioactive material. Imaging is obtained immediately afterwards to evaluate for any perfusion defects.

Bedside cardiac ultrasound may be useful in guiding clinicians for faster diagnosis.  Signs of right ventricular strain from PE include right ventricular enlargement, leftward septal shift (“bowing” of the septum of the RV into the LV). A bedside echocardiogram may also reveal decreased movement of the free right ventricular wall with hyperkinesis of the right ventricular apex (McConnell’s Sign).

Management and treatment of PE will depend on risk stratification.

1) Hemodynamically unstable “massive PE” – thrombolytic therapy should be initiated, as these patients are at high risk for cardiogenic shock.  The currently accepted standard indication for thrombolytic therapy include those with a SBP < 90.  In select patients, catheter directed thrombolysis or thrombectomy should be considered in consultation with a thoracic surgeon.   

2) In all other patients (including those with hemodynamically unstable while awaiting thrombolytic therapy), should receive anticoagulation.  Most patients should receive low-molecular weight heparin or fondaparinux.  If there is renal insufficiency or there is the possibility of thrombolytic therapy, IV unfractionated heparin should be used, as this is easier to titrate and easier to stop if needed given its short half-life.

Current standards of care dictate that all patients with PE of all types be admitted to the hospital for further management.  In patients with a first time PE, anticoagulation therapy should continue for 3 months.