The outcome of this course is to enable the participants to understand the pathophysiology, diagnosis criteria and treatment of acute pulmonary embolism.
After completing this course, the learner will be able to
Pulmonary embolism and deep vein thrombosis are usually classified together for epidemiologic purposes. Venous thromboembolism is the term used to denote both pulmonary embolism and deep vein thrombosis. Together they constitute the third leading cause of death from cardiovascular diseases second only to myocardial infarction and stroke. In hospitalized patients, the incidence of pulmonary embolism related deaths is 7% of all patients diagnosed. There are approximately 900,000 people in the US affected with venous thromboembolism. 300,000 of those affected die from venous thromboembolism each year. 100,000 of those deaths are attributed to acute pulmonary embolism alone. 1,2
The costs associated with deep vein thrombosis has been estimated as up to $7.5 billion each year. The costs associated with pulmonary embolism is estimated to be between $8.5 to $19.8 billion. Most of these costs are associated to the hospital stay. 3
Patients with deep vein thrombi are ten times more likely to have a lower extremity thrombus than an upper extremity thrombus. The more proximal the thrombus within the extremity, the more likely it is to embolize into the lungs as a pulmonary embolus.
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When a thrombus dislodges from a deep vein within the venous system, it travels towards the venous cava and then it progresses to the right atrium, then goes through the tricuspid valve before making its way into the right ventricle. Once it is the right ventricle, it passes through the pulmonary valve (pulmonic valve) before making its way to the lungs. An extremely large clot may get lodged at the bifurcation between the right and left pulmonary arteries; this is known as a “saddle” pulmonary embolus.
Although upper extremity clots occur much less frequently than lower extremity clots, they tend to occur much more frequently with the placement of pacemakers, implantable cardiac defibrillators and long term central venous access used for dialysis, nutrition and chemotherapy. The bigger the size of the central venous line, the higher the risk of a deep vein thrombus. Decreasing the size of the central venous access can significantly reduce the risk of pulmonary embolism. 4 Another risk associated with the placement of upper extremity central venous lines is superior vena cava syndrome.
After a thrombus occludes a deep vein, vascular drainage within the extremity is altered leading to increased pressure within the vessel which is transmitted to the capillaries angiopathy within these small vessels. Physical examination associated with chronic deep vein thrombosis include; skin ulceration, varicose veins and abnormal pigmentation. Chronic deep vein thrombosis significantly reduces the patient’s quality of life due to decreased mobility and pain. These patients are usually treated with the use of compression stockings which are worn below the knees. These stockings help improve the patient’s quality of life.
Patients with a superficial vein thrombosis are at increased risk for deep vein thrombosis (six times the risk of the normal population) as well as increased risk for acute pulmonary embolism (four times higher than the normal population). Most of these patients are treated with anticoagulation.
Risk factors associated with deep vein thrombosis include; diabetes mellitus, obesity and smoking. Patients who are diagnosed with an acute pulmonary embolus have an increased risk of stroke or myocardial infarction. 5
Other risk factors associated with venous thromboembolism: increased age, personal and/or family history of a deep vein thrombosis and decreased mobility. Congestive heart failure, recent surgery and recent stroke are also linked to increased risk of venous thromboembolism. Use of oral contraceptives, hormone replacement therapy and pregnancy have all been linked to increased risk of venous thromboembolism. Patients on long flights and those with decreased mobility are also at increased. Although the risk of pulmonary embolism with long plane rides is frequently discussed, the risk of an associated fatal pulmonary embolism is extremely rare. The true incidence of a fatal pulmonary embolism from a plane ride is less than 1 in 1 million patients. 6
Hypercoagulations syndromes are also linked to increased risk of venous thromboembolism. Examples of hypercoagulation syndromes include: antiphospholipid syndrome, protein C deficiency, protein S deficiency, factor V leiden deficiency and antithrombin deficiency. The most common risk factors associated with deep vein thromboembolism include; a previous deep vein thrombus, hormone use, high BMI and thrombophilia. 7,8
This accounts for 10% or less of all pulmonary embolism. A massive pulmonary embolism is defined as a large acute pulmonary embolism associated with hemodynamic instability. It usually presents as a bilateral clot within the left and right pulmonary arteries. A bilateral pulmonary embolism in both main pulmonary arteries is sometimes called a “saddle” pulmonary embolism. Patients with massive pulmonary embolism are at risk for cardiogenic shock and eventually multisystem organ failure if not treated. In these patients, dyspnea is the most common clinical presentation. Often, they present in hypotension with evidence of poor perfusion. Radiographically these patients usually have evidence of right heart strain seen on CT imaging as an increased RV to LV ratio.
Treatment involves mechanical and pharmacologic catheter directed therapy, surgical embolectomy, inferior vena cava filter placement, anticoagulation with intravenous heparin as well as systemic thrombolysis. Patients in this group usually require intensive care interventions including ventilatory support and vasopressor administration.
Submassive pulmonary emboli constitute up to 25% of patients. Patients with submassive pulmonary emboli are usually hemodynamically stable as opposed to massive pulmonary embolism. Radiologically, massive and submassive pulmonary emboli may be identical. As such “saddle” emboli are commonly seen in cases of submassive embolism. This implies massive pulmonary emboli can only be diagnosed clinically not radiographically. Radiology helps to localize the extent of the clot which helps guide clinical interventions. In cases of submassive pulmonary emboli, the patient may have elevated markers of right heart strain (such as elevated BNP levels) even though they are hemodynamically stable. There may be radiographic evidence of right heart strain which is usually seen as an increased RV to LV ratio. Occasionally, patients in this group may be asymptomatic which is misleading as they will often present with recurrent pulmonary emboli even with the administration of anticoagulation therapy. 9
Treatment usually involves the initiation of intravenous heparin. In patients with an increased risk of bleeding, the decision to start systemic interventions can be controversial as clinicians have to seriously weigh the decision of preventing cardiovascular collapse against the risk of hemorrhagic stroke. In patients with a low risk of bleeding, the treatment interventions are identical to those used in patients with massive pulmonary embolism. Most patients in this group may require increased interventions including ventilatory support as well as vasopressor administration.
Low risk pulmonary emboli are approximately 65% of all pulmonary emboli. These emboli are small to moderate sized pulmonary emboli usually found in segmental and submental pulmonary vessels. Patients in this category typically present with normal hemodynamic stability, occasionally with shortness of breath, most of them may be asymptomatic. Treatment involves anticoagulation with subcutaneous heparin as a bridge to warfarin therapy. Another option is to administer rivaroxaban (Xarelto) as a single agent. Administration of anticoagulation usually results in good clinical outcomes in this patient cohort.
This is a pulmonary embolus which presents as a cerebrovascular accident (stroke). It typically presents in patients with a deep vein thrombosis that embolizes to the arterial system via a patent foramen ovale. Normally, a deep vein thrombus should embolize to the lungs which act as a sieve for body. To the get through to the arteries without going through the lungs, the thrombus must have a short cut which is usually a patent foramen ovale. 10
Traditionally pulmonary emboli originate from thrombi which lodge within the pulmonary vessels. There are other sources of pulmonary emboli which include; air, tumor, fat and amniotic fluid (pregnant women). Air emboli tend to occur in patients with central venous catheters either during placement, removal or manipulation of the central line. Fat emboli are common seen in trauma patients with long bone fractures. Pregnant women who are diagnosed with amniotic fluid emboli tend to be critically ill and usually require vasopressor and ventilatory support.
Drug users are the group most commonly diagnosed with septic pulmonary emboli. These occur because of self-injection of drugs and other contaminants such as hair and talc leading to endocarditis and vegetations on the heart valves. Eventually these vegetations in the heart are showered into the lungs. The right sided heart valves (tricuspid and pulmonary valves) are usually affected in patients with endocarditis. Septic emboli tend to be multiple and bilateral. Each embolus serves as a focus of infection. Patients with septic emboli should be treated with antibiotics.
Patients with pulmonary emboli may progress to have a full pulmonary infarct. Pulmonary infarction usually presents as pleuritic chest pain. Pleuritic chest pain is defined as pain which is made worse with breathing movement. Occasionally, the pleuritic chest pain is accompanied by hemoptysis (bleeding from the airway). Patients with pulmonary emboli that progress unto pulmonary infarction usually have peripheral emboli lodged in smaller subsegmental pulmonary arteries. Typically, pulmonary infarcts develop about a week after diagnosis of the pulmonary embolus. Other clinical manifestations of pulmonary infarction include; elevated white blood cell count, fevers, and an elevated erythrocyte sedimentation rate. 11
The most commonly reported symptom with pulmonary embolism is dyspnea which is reported 82 - 85% of the time. Tachypnea is reported in 30 - 60% of patients. Other commonly symptoms include; cough, hemoptysis, chest pain, wheezing, syncope, fever, diaphoresis, apprehension and evidence of a DVT such as swelling and tenderness in the extremities.
Acute pulmonary embolism can be difficult to diagnose because it shares similar signs and symptoms with other illnesses such as acute myocardial infarction, pneumonia and congestive heart failure. In addition, acute pulmonary emboli can occur simultaneously with these other diagnoses. Clinicians must have a high clinical suspicion for acute pulmonary embolism. 12
Tachypnea and dyspnea are the most frequently reported sign and symptom of acute pulmonary embolism. Cyanosis, severe dyspnea and syncope tend to indicate a life threatening pulmonary embolism. Severe pleuritic chest pain on the other hand is usually associated with small distal pulmonary emboli. Patients have also reported feeling increased anxiety as a presenting symptom with a diagnosis of pulmonary embolism.
The best clinical criteria for the diagnosis of pulmonary embolism currently is the Wells Criteria. The Wells criteria is based on clinical criterion which are ascribed a specific score. After the patient is assessed, the score is summed up. Patients with a score greater than 4 have a high probability of having a pulmonary embolism. Patients with a Wells score of 4 or less do not have a high probability of having a pulmonary embolism. 11
Of note, the clinical criteria are not equally weighted.
The Revised Geneva criteria is a tool used as an alternative to the Well’s criteria. It is also based on a point system. 13
A score greater than 5 implies that a pulmonary embolism is likely. A score less than or equal to 5 makes a pulmonary embolism unlikely.
This is a blood screening test that relies on the principle that patients with a pulmonary embolism inadequate fibrinolysis therefore they have increases levels of fibrin in their blood. These fibrin fibers cannot be effectively broken down so some of it is broken down to D-dimer molecules. Although increased levels of D-dimers are sensitive for pulmonary embolism, they are not specific. Patients with malignancy, myocardial infarction, sepsis, or even in the postoperative setting can have elevated D-dimer levels. Ideally, D-dimer levels should be used to screen outpatients who present with suspected pulmonary embolism in the emergency department setting. Hospitalized patients tend to have elevated D-dimer levels and they should not be screened for PE using the D-dimer assay. 12
An EKG is used to exclude a myocardial infarction and acute pericarditis. Also, the EKG can clue the clinicians to the presence of right heart strain which is a concerning sign. Right strain on an EKG can present in multiple ways depending on the underlying etiology. Typically, it presents as ST segment and T wave abnormalities most prominent in the anterior leads (V1-V4). Other causes of increased right heart strain include; pulmonary hypertension, obstructive and restrictive pulmonary diseases including chronic obstructive pulmonary disease and asthma respectively.
It is not uncommon to see a complete normal chest x-ray in the setting of a positive pulmonary embolism study. As a matter of fact, a complete normal chest x-ray in the setting of severe respiratory distress raises concern for a massive pulmonary embolism. Occasionally, there are certain signs seen on x-ray that can suggest the presence of a pulmonary embolism. Such as, the Westermark sign which is defined as the scarcity of pulmonary vascularity within a certain region of the lung. Hampton’s hump is another sign used to indicate the presence of a pulmonary embolism. It refers to a wedge-shaped opacity in the periphery of the lung above the diaphragm.
Another utility of the chest radiograph is to rule out other conditions which may confound or mimic the diagnosis of pulmonary embolism. Such as pneumonia or pneumothorax. However, it is not impossible to have a pneumonia or pneumothorax and a pulmonary embolism.
This is a nuclear medicine test which uses radioactive radiotracers to evaluate pulmonary ventilation (V) and pulmonary perfusion (Q). Usually 2 radiotracers are most commonly used; Technetium 99 DTPA is used for the ventilation portion of the test while Technetium 99 MAA is used for the perfusion portion of the test. The ventilation and flow images are evaluated together to see if there is a mismatch between perfusion and ventilation. If there is a mismatch between ventilation and perfusion, this raises concern for a pulmonary embolism. A chest x-ray must be performed to help with interpretation of this test to rule out other diagnoses which may confound the differential diagnosis. For example, atelectasis (lung collapse) may cause a mismatch between perfusion and ventilation. V/Q scan result are report as low, intermediate and high probability for pulmonary embolism.
Common reasons why clinicians obtain a V/Q scan instead of a CT pulmonary angiogram:
Chest Computed Tomography (CT) pulmonary angiogram commonly known as a CT pulmonary embolism (CT PE) protocol is the primary test used to evaluate patients with a suspected pulmonary embolism. It is performed by administering iodinated contrast intravenously. A multirow detector CT scan is then used to scan the patient and 3 dimensional images are eventually reconstructed allowing for better visualization of the thrombus. 11
The advantages of CT include; fast acquisition - the entire study is performed in a matter of seconds. It is easily accessible- CT scans are commonly available in almost all emergency departments and most urgent care settings. In addition, CT scan is useful for ruling out other diagnoses which may be responsible for the patient’s clinical presentation. Finally, CT can assess for right heart strain which is can suggest the presence of a submassive pulmonary embolus. A massive pulmonary embolus can never be diagnosed on CT, it is a clinical diagnosis. 11
Echocardiography is not commonly ordered for the evaluation of acute pulmonary embolism. It is useful for evaluating right heart strain as well as the presence of a thrombus within the right atrium.
Up to 50% of the patients with pulmonary embolism have no diagnosis of a deep vein thrombus. 5 A lower extremity duplex ultrasound is commonly ordered to rule out a deep vein thrombus. It is often more difficult to diagnose a deep vein thrombus in the upper extremity.
Traditionally this was the gold standard for the diagnosis of pulmonary embolism. However, with the advent of CT pulmonary angiogram, this is no longer used for diagnosis. Nowadays, it is still being used for pharmacologic and mechanical interventions in patients with large emboli especially saddle emboli in an unstable patient.
Once a patient presents with clinical concern for a pulmonary embolism, the first step is to determine if they are stable or unstable. If they are unstable, they should go straight to CT for evaluation with a CT pulmonary angiogram. If they are stable, they should have a D-dimer level drawn. If positive, they should have a CT pulmonary angiogram performed. A normal D-dimer level rules out a pulmonary embolism. 5
Differential diagnosis to be considered in patients who present with symptoms of pulmonary embolism is myocardial infarction, pneumothorax, pericarditis, congestive heart failure, pleuritis, pneumonia, chest pain, esophageal rupture, peptic ulcer, pericardial tamponade, aortic dissection pericardial tamponade and anxiety disorder.
Management of pulmonary embolism can vary significantly based on the burden of the thrombus as well as the clinical symptoms associated with the thrombus. In general, low risk patients are treated with anticoagulation. Whereas high risk patients may require admission into an intensive care unit, surgical thrombectomy, catheter assisted thrombolysis using mechanical and pharmacologic techniques, inferior vena cava filter placement and systemic thrombolysis.
There are 3 critical parts required for risk stratification and these are; the clinical evaluation, elevated cardiac biomarkers and right heart strain. The need to stratify patients with pulmonary embolism led to the creation of the Pulmonary Embolus Severity Index (PESI). PESI is a clinical prediction tool used to predict the risk of morbidity and mortality. It is based on several factors including age greater than 80, temperature less than 36 degree Celsius, heart rate greater than 110 beats per minute, systolic blood pressure less than 100, altered oxygen saturation with a pulse oximeter reading less than 90%, respiratory rate greater than 30, history of cancer, history of chronic lung disease, history of heart failure, altered mental status and male sex. PESI uses the 11 clinical indicators listed above without the use of imaging or laboratory parameters. 5, 14
Management of acute pulmonary emboli in the intensive care setting requires the formation of a Pulmonary Embolism Response Team (PERT). A PERT team is like a ST segment elevation myocardial infarction (STEMI) response team. It is usually made up of clinicians from different disciplines and specialties including nursing, pharmacy, interventional radiology, interventional cardiology, internal medicine and surgery. To make the correct treatment decision, it is important to fully understand the risks and benefits of each treatment option. As such, each clinician is called to weigh in from their clinical perspective. The PERT team reviews each case individually and in conjunction with the patient’s family members and care team a consensus decision is made regarding the best treatment option. It is important to each hospital establishes a pulmonary embolism protocol. 15
The PERT is usually activated with a single phone call or page. Once it is activated, each member of the team must have access to the medical records to review the information in a timely manner. One of the first decisions that a PERT team makes is deciding the floor to which the patient is to be admitted. Some patients are better managed in an intensive care unit while others can be managed on a medical-surgical unit.
Unless it is contraindicated, anticoagulation should be initiated in every patient diagnosed with a pulmonary embolism. Heparin administered intravenously is the usual initial therapeutic agent. After diagnosis, the next step is to determine if the patient has a massive or a submassive pulmonary embolism. High risk clues of a submassive pulmonary embolism include tachypnea, tachycardia and dyspnea. There should be a high clinical suspicion of a submassive pulmonary embolism in patients who present with syncope. Since syncope may indicate hemodynamic instability. Sometimes the PERT team may decide to initiate anticoagulation initiation prior to the definitive diagnosis of pulmonary embolism when clinical suspicion is high.
Heparin or low molecular weight heparin such as Lovenox should be initiated until the patient can be bridged to warfarin. Heparin can be administered intravenously or subcutaneously. Lovenox is usually administered subcutaneously. Warfarin usually takes 5-7 days to reach therapeutic levels in the blood stream therefore a Lovenox bridge is usually required. Systemic fibrinolysis has been traditionally used in patients with high risk pulmonary embolism. Fibrinolytic agents are different from anticoagulants. Examples of systemic fibrinolytics include; alteplase, urokinase and streptokinase. Using IV fibrinolytic agents has been shown to be associated with hemodynamic stabilization and lower rate of recurrent pulmonary embolism. However, these benefits come with an increased risk of bleeding including intracranial hemorrhage. 11
Catheter therapies are usually administered by interventional radiology or interventional cardiology or vascular surgery. This may involve the injection of low dose fibrinolytic agents. It also involves mechanical fragmentation and subsequent aspiration of the clot. Large clots can be difficult to remove. Overall, catheter directed therapies are better suited for hemodynamically stable patients. Complications associated with catheter directed therapy include; pulmonary artery vessel injury, bleeding and hemodynamic instability. 16
Surgical embolectomy is considered a last resort for patients with massive pulmonary embolism. This technique was first introduced in the 1960’s. Currently the morality associated with this procedure is less than 6% which is remarkably low compared to the 50% mortality rate it had when it was first introduced. 17, 18 Patients undergoing surgical embolectomy are put on anticoagulation.
Placement of an inferior vena cava (IVC) filter is indicated in patients with acute pulmonary embolism who have an absolute contraindication to anticoagulation or in patients who have recurrent deep vein thrombosis or pulmonary clots despite anticoagulation. 19 The location of the filter depends on the involvement of the renal vein. In general, retrievable IVC filters are associated with less complications.
Mr. Jones is admitted to the Step-down unit for congestive heart failure. He is on day 4 of admission and relatively stable. He suddenly becomes short of breath with oxygen demands increasing from room air to 6L via nasal cannula. He reports having chest palpitations, worsening right leg swelling and a feeling of impending doom. You are the nurse taking care of Mr. Jones, what are your next steps?
Discussion: Given that the patient is has had a change in status and is now unstable, the nurse should call for rapid response team activation. This will allow the nurse to have help at the bedside to help stabilize the patient. Vital signs should be obtained immediately and repeated every 5 mins. In most hospitals a rapid response team will necessitate that a provider (physician, nurse practitioner or physician assistant) be present at the bedside. If there is suspicion that the patient is fluid overloaded, this can be confirmed by reviewing the intake and output record and/or reviewing a stat chest x-ray. If the patient does not respond to a diuretic in a few minutes, the swollen leg should clue the clinical team on the possibility of a pulmonary embolism. The swollen leg is a pertinent fact that the bedside nurse should bring up to the rest of the clinical team immediately.
Once the team was made aware of the patient’s swollen leg, a CT pulmonary angiogram was ordered immediately. The patient was diagnosed with a saddle pulmonary embolus. He became hemodynamically unstable while in the CT scanner. After completion of the study he was transferred to the interventional radiology suite for possible intervention. A heparin drip was started while the patient was in holding.
Caring for patients diagnosed with a venous thromboembolism comes at a significant cost. A study performed in 2015 showed that patients with an ICU stay during their hospitalization had higher costs as would be expected. Interestingly, the costs of care were higher during the first 3 days of hospitalization for both patients with deep vein thrombosis and pulmonary embolism. However, the overall costs during those first 3 days were higher when caring for patients diagnosed with a deep vein thrombus compared to patients diagnosed with a pulmonary embolism.