Pulmonary embolism

Symptoms of pulmonary embolism are typically sudden in onset and may include one or many of the following: dyspnea (shortness of breath), tachypnea (rapid breathing), chest pain of a "pleuritic" nature (worsened by breathing), cough and hemoptysis (coughing up blood). More severe cases can include signs such as cyanosis (blue discoloration, usually of the lips and fingers), collapse, and circulatory instability because of decreased blood flow through the lungs and into the left side of the heart. About 15% of all cases of sudden death are attributable to PE. On physical examination, the lungs are usually normal. Occasionally, a pleural friction rub may be audible over the affected area of the lung (mostly in PE with infarct). A pleural effusion is sometimes present that is exudative (fluid that leaks out of blood vessels). This is detectable by decreased percussion note, audible breath sounds, and vocal resonance. The strain on the right ventricle may be detected as a left parasternal heave, a loud pulmonary component of the second heart sound, or raised jugular venous pressure. As smaller pulmonary emboli tend to lodge in more peripheral areas without collateral circulation, they are more likely to cause lung infarction and small effusions (both of which are painful), but not hypoxia, dyspnea, or hemodynamic instability such as tachycardia. Larger PEs, which tend to lodge centrally, typically cause dyspnea, hypoxia, low blood pressure, fast heart rate and fainting, but are often painless because there is no lung infarction due to collateral circulation. The classic presentation for PE with pleuritic pain, dyspnea, and tachycardia is likely caused by a large fragmented embolism causing both large and small PEs. Thus, small PEs are often missed because they cause pleuritic pain alone without any other findings and large PEs are often missed because they are painless and mimic other conditions often causing ECG changes and small rises in troponin and brain natriuretic peptide levels. PEs are sometimes described as massive, submassive, and nonmassive depending on the clinical signs and symptoms. Although the exact definitions of these are unclear, an accepted definition of massive PE is one in which there is hemodynamic instability. This is a cause of obstructive shock, which presents as sustained low blood pressure, slowed heart rate, or pulselessness. ==Risk factors==

as seen with signs of redness and swelling in the right leg is a risk factor for PE. About 90% of emboli are from a deep vein thrombosis located above the knee termed a proximal DVT, which includes an iliofemoral DVT. The rare venous thoracic outlet syndrome can also be a cause of DVTs, especially in young men without significant risk factors. DVTs are at risk for dislodging and migrating to the lung circulation. The conditions are generally regarded as a continuum known as a venous thromboembolism (VTE). VTE is much more common in immunocompromised individuals as well as individuals with comorbidities including: • Those that undergo orthopedic surgery at or below the hip without prophylaxis. • No linkage has been found to those taking progestin-only oral contraceptives. The development of thrombosis is classically due to a group of causes named Virchow's triad (alterations in blood flow, factors in the vessel wall, and factors affecting the properties of the blood). Often, more than one risk factor is present. • Alterations in blood flow: immobilization (after surgery, long-haul flight), injury, pregnancy (also procoagulant), obesity (also procoagulant), cancer (also procoagulant) • Factors in the vessel wall: surgery, catheterizations causing direct injury ("endothelial injury") • Factors affecting the properties of the blood (procoagulant state): • Estrogen-containing medication (transgender hormone therapy, menopausal hormone therapy and hormonal contraceptives) • Pulmonary hypertension ==Diagnosis==

in a person with a right lower lobe pulmonary embolism To diagnose a pulmonary embolism, a review of clinical criteria to determine the need for testing is recommended. Although a CTPA is preferred, other tests can be done. For example, a proximal lower limb compression ultrasound (CUS) can be used. A new prediction score for PE was created in 1998. This prediction rule was revised by Wells et al. in 2000. In the 2000 publication, Wells proposed two different scoring systems using cutoffs of 2 or 4 with the same prediction rule, and also included D-dimer testing in the rule-out of PE in low probability patients. An additional version, the "modified extended version", using the more recent cutoff of 2 but including findings from Wells's initial studies Most recently, a further study reverted to Wells's earlier use of a cutoff of 4 points There are additional prediction rules for PE, such as the Geneva rule. More importantly, the use of any rule is associated with reduction in recurrent thromboembolism. The Wells score: • clinically suspected DVT – 3.0 points • alternative diagnosis is less likely than PE – 3.0 points • tachycardia (heart rate > 100) – 1.5 points • immobilization (≥ 3d)/surgery in previous four weeks – 1.5 points • history of DVT or PE – 1.5 points • hemoptysis – 1.0 points • malignancy (with treatment within six months) or palliative – 1.0 points Traditional interpretation • Score >6.0 – High (probability 59% based on pooled data) Pulmonary embolism rule-out criteria The pulmonary embolism rule-out criteria (PERC) helps assess people in whom pulmonary embolism is suspected, but unlikely. Unlike the Wells score and Geneva score, which are clinical prediction rules intended to risk stratify people with suspected PE, the PERC rule is designed to rule out the risk of PE in people when the physician has already stratified them into a low-risk category. The PERC rule has a sensitivity of 97.4% and specificity of 21.9% with a false negative rate of 1.0% (16/1666). Blood tests In people with a low or moderate suspicion of PE, a normal D-dimer level (shown in a blood test) is enough to exclude the possibility of thrombotic PE, with a three-month risk of thromboembolic events being 0.14%. D-dimer is highly sensitive but not specific (specificity around 50%). In other words, a positive D-dimer is not synonymous with PE, but a negative D-dimer is, with a good degree of certainty, an indication of absence of a PE. A low pretest probability is also valuable in ruling out PE. The typical cut off is 500 μg/L, although this varies based on the assay. When a PE is being suspected, several blood tests are done to exclude important secondary causes of PE. This includes a full blood count, clotting status (PT, aPTT, TT), and some screening tests (erythrocyte sedimentation rate, kidney function, liver enzymes, electrolytes). If one of these is abnormal, further investigations might be warranted to the issue. Troponin levels are increased in between 16 and 47% with pulmonary embolism. Imaging In typical people who are not known to be at high risk of PE, imaging is helpful to confirm or exclude a diagnosis of PE after simpler first-line tests are used. Medical societies recommend tests such as the D-dimer to first provide supporting evidence for the need for imaging, and imaging would be done if other tests confirmed a moderate or high probability of finding evidence to support a diagnosis of PE. Ultrasound of the legs can confirm the presence of a PE but cannot rule it out. CT pulmonary angiography CT pulmonary angiography (CTPA) is a pulmonary angiogram obtained using computed tomography (CT) with radiocontrast rather than right heart catheterization. Its advantages are that it is accurate, it is non-invasive, it is more often available, and it may identify other lung disorders in case there is no pulmonary embolism. The accuracy and non-invasive nature of CTPA also make it advantageous for people who are pregnant. File:Computed tomograph of pulmonary vessels.jpg|On CT scan, pulmonary emboli can be classified according to the level along the arterial tree. File:SegandSubsegPE.png|Segmental and subsegmental pulmonary emboli on both sides File:Pulmonary embolism CTPA.JPEG|CT pulmonary angiography showing a "saddle embolus" at the bifurcation of the main pulmonary artery and thrombus burden in the lobar arteries on both sides File:CT of lung infarction with reverse halo sign, annotated.png|Pulmonary embolism (white arrow) that has been long-standing and has caused a lung infarction (black arrow) seen as a reverse halo sign Assessing the accuracy of CT pulmonary angiography is hindered by the rapid changes in the number of rows of detectors available in multidetector CT (MDCT) machines. According to a cohort study, single-slice spiral CT may help diagnose detection among people with suspected pulmonary embolism. In this study, the sensitivity was 69% and specificity was 84%. In this study which had a prevalence of detection was 32%, the positive predictive value of 67.0% and negative predictive value of 85.2%. However, this study's results may be biased due to possible incorporation bias, since the CT scan was the final diagnostic tool in people with pulmonary embolism. The authors noted that a negative single-slice CT scan is insufficient to rule out pulmonary embolism on its own. A separate study with a mixture of 4-slice and 16-slice scanners reported a sensitivity of 83% and a specificity of 96%, which means that it is a good test for ruling out a pulmonary embolism if it is not seen on imaging and that it is very good at confirming a pulmonary embolism is present if it is seen. This study noted that additional testing is necessary when the clinical probability is inconsistent with the imaging results. CTPA is non-inferior to VQ scanning, and identifies more emboli (without necessarily improving the outcome) compared to VQ scanning. Ventilation/perfusion scan (A) After inhalation of 20 mCi of Xenon-133 gas, scintigraphic images were obtained in the posterior projection, showing uniform ventilation to lungs. (B) After intravenous injection of 4 mCi of Technetium-99m-labeled albumin, scintigraphic images are shown here in the posterior projection. This and other views showed decreased activity in multiple regions. A ventilation/perfusion scan (or V/Q scan or lung scintigraphy) shows that some areas of the lung are being ventilated but not perfused with blood (due to obstruction by a clot). Low probability diagnostic tests/non-diagnostic tests Tests that are frequently done that are not sensitive for PE, but can be diagnostic. • Chest X-rays are often done on people with shortness of breath to help rule out other causes, such as congestive heart failure and rib fracture. Chest X-rays in PE are rarely normal, but usually lack signs that suggest the diagnosis of PE (for example, Westermark sign, Hampton's hump). • Ultrasonography of the legs, also known as leg doppler, in search of deep venous thrombosis (DVT). The presence of DVT, as shown on ultrasonography of the legs, is in itself enough to warrant anticoagulation, without requiring the V/Q or spiral CT scans (because of the strong association between DVT and PE). This may be a valid approach in pregnancy, in which the other modalities would increase the risk of birth defects in the unborn child. However, a negative scan does not rule out PE, and low-radiation dose scanning may be required if the mother is deemed at high risk of having a pulmonary embolism. The main use of ultrasonography of the legs is therefore in those with clinical symptoms suggestive of deep vein thrombosis. Fluoroscopic pulmonary angiography revealing clot (labeled A) causing a central obstruction in the left main pulmonary artery. ECG tracing is shown at the bottom. Historically, the gold standard for diagnosis was pulmonary angiography by fluoroscopy, but this has fallen into disuse with the increased availability of non-invasive techniques that offer similar diagnostic accuracy. Electrocardiogram of approximately 100 beats per minute, large S wave in Lead I, moderate Q wave in Lead III, inverted T wave in Lead III, and inverted T waves in leads V1 and V3 The primary use of the ECG is to rule out other causes of chest pain. An electrocardiogram (ECG) is routinely done on people with chest pain to quickly diagnose myocardial infarctions (heart attacks), an important differential diagnosis in an individual with chest pain. While certain ECG changes may occur with PE, none are specific enough to confirm or sensitive enough to rule out the diagnosis. This is occasionally present (occurring in up to 20% of people), but may also occur in other acute lung conditions, and, therefore, has limited diagnostic value. The most commonly seen signs in the ECG are sinus tachycardia, right axis deviation, and right bundle branch block. Sinus tachycardia, however, is still only found in 8–69% of people with PE. ECG findings associated with pulmonary emboli may suggest a worse prognosis since the six findings identified with RV strain on ECG (heart rate > 100 beats per minute, S1Q3T3, inverted T waves in leads V1-V4, ST elevation in aVR, complete right bundle branch block, and atrial fibrillation) are associated with increased risk of circulatory shock and death. Cases with inverted T in leads V1-3 are suspected of PE or inferior myocardial infarction. PE cases show inverted T waves in leads II and aVF, but inferior myocardial infarction cases do not show inverted T waves in II and aVF. Echocardiography In massive and submassive PE, dysfunction of the right side of the heart may be seen on echocardiography, an indication that the pulmonary artery is severely obstructed and the right ventricle, a low-pressure pump, is unable to match the pressure. Some studies (see below) suggest that this finding may be an indication for thrombolysis. Not every person with a (suspected) pulmonary embolism requires an echocardiogram, but elevations in cardiac troponins or brain natriuretic peptide may indicate heart strain and warrant an echocardiogram, and be important in prognosis. The specific appearance of the right ventricle on echocardiography is referred to as the ''McConnell's sign''. This is the finding of akinesia of the mid-free wall but a normal motion of the apex. This phenomenon has a 77% sensitivity and a 94% specificity for the diagnosis of acute pulmonary embolism in the setting of right ventricular dysfunction. of a pulmonary artery from autopsy. It shows a fat embolism (seen as multiple empty globular spaces on this H&E stain since its processing dissolves fat). There is a bone marrow fragment in the middle, and multiple single hematopoietic cells in the blood, being evidence of fracture as the source of the embolism. File:UOTW 2 - Ultrasound of the Week 1.webm|Ultrasound of the heart showing signs of PE ==Prevention==

Pulmonary embolism may be preventable in those with risk factors. People admitted to the hospital may receive preventative medication, including unfractionated heparin, low molecular weight heparin (LMWH), or fondaparinux, and anti-thrombosis stockings to reduce the risk of a DVT in the leg that could dislodge and migrate to the lungs. Following the completion of anticoagulation in those with prior PE, long-term aspirin is useful to prevent recurrence. ==Treatment==

Anticoagulant therapy is the mainstay of treatment. Acutely, supportive treatments, such as oxygen or analgesia, may be required. People are often admitted to hospital in the early stages of treatment and tend to remain under inpatient care until the INR has reached therapeutic levels (if warfarin is used). Increasingly, however, low-risk cases are managed at home in a fashion already common in the treatment of DVT. Evidence to support one approach versus the other is weak. Anticoagulation Anticoagulant therapy is the mainstay of treatment. For many years, vitamin K antagonists (warfarin or less commonly acenocoumarol or phenprocoumon) have been the cornerstone. As vitamin K antagonists do not act immediately, initial treatment is with rapidly acting injectable anticoagulants: unfractionated heparin (UFH), low molecular weight heparin (LMWH), or fondaparinux, while oral vitamin K antagonists are initiated and titrated (usually as part of inpatient hospital care) to the international normalized ratio, a test that determines the dose. According to the same review, LMWH reduced the incidence of recurrent thrombotic complications and reduced thrombus size when compared to heparin. There was no difference in overall mortality between participants treated with LMWH and those treated with unfractionated heparin. In people with cancer who develop pulmonary embolism, therapy with a course of LMWH is favored over warfarin or other oral anticoagulants. For those with small PEs (known as subsegmental PEs) the effects of anticoagulation are unknown as it has not been properly studied as of 2020. Thrombolysis Massive PE causing hemodynamic instability (shock and/or low blood pressure, defined as a systolic blood pressure 15 min if not caused by new-onset arrhythmia, hypovolemia, or sepsis) is an indication for thrombolysis, the enzymatic destruction of the clot with medication. In this situation, it is the best available treatment for those without contraindications and is supported by clinical guidelines. It is also recommended in those in cardiac arrest with a known PE. Catheter-directed thrombolysis (CDT) is a new technique found to be relatively safe and effective for massive PEs. This involves accessing the venous system by placing a catheter into a vein in the groin and guiding it through the veins by using fluoroscopic imaging until it is located next to the PE in the lung circulation. Medication that breaks up blood clots is released through the catheter so that its highest concentration is directly next to the pulmonary embolus. CDT is performed by interventional radiologists or vascular surgeons, and in medical centers that offer CDT, it may be offered as a first-line treatment. Catheter-based ultrasound-assisted thrombolysis is being investigated. The use of thrombolysis in non-massive PEs is still debated. Some have found that the treatment decreases the risk of death and increases the risk of bleeding including intracranial hemorrhage. Others have found no decrease in the risk of death. Inferior vena cava filters should be removed as soon as it becomes safe to start using anticoagulation. Chronic pulmonary embolism leading to pulmonary hypertension (known as chronic thromboembolic hypertension) is treated with a surgical procedure known as a pulmonary thromboendarterectomy. ==Prognosis==

Fewer than 5 to 10% of symptomatic PEs are fatal within the first hour of symptoms. Improvement slows thereafter and some deficits may be permanent. There is controversy over whether small subsegmental PEs need treatment at all and some evidence exists that patients with subsegmental PEs may do well without treatment. Once anticoagulation is stopped, the risk of a fatal pulmonary embolism is 0.5% per year. Mortality from untreated PEs was said to be 26%. This figure comes from a trial published in 1960 by Barrit and Jordan, which compared anticoagulation against a placebo for the management of PE. Barritt and Jordan performed their study in the Bristol Royal Infirmary in 1957. This study is the only placebo-controlled trial ever to examine the place of anticoagulants in the treatment of PE, the results of which were so convincing that the trial has never been repeated as to do so would be considered unethical. That said, the reported mortality rate of 26% in the placebo group is probably an overstatement, given that the technology of the day may have detected only severe PEs. Predicting mortality The PESI and sPESI (= simplified Pulmonary Embolism Severity Index) scoring tools can estimate the mortality of patients. The Geneva prediction rules and Wells criteria are used to calculate the pre-test probability of patients to predict who has a pulmonary embolism. These scores are tools to be used with clinical judgment in deciding diagnostic testing and types of therapy. The PESI algorithm comprises 11 routinely available clinical variables. It puts the subjects into one of five classes (I–V), with 30-day mortality ranging from 1.1% to 24.5%. Those in classes I and II are low-risk and those in classes III–V are high-risk. ==Epidemiology==

There are roughly 10 million cases of pulmonary embolisms per year. In the United States, pulmonary embolisms are the primary cause of at least 10,000 to 12,000 deaths per year and a contributing cause in at least 30,000 to 40,000 deaths per year. In Europe, an average of approximately 40,000 deaths per year with pulmonary embolism as the primary cause was reported between 2013 and 2015, a conservative estimate because of potential underdiagnosis. == References ==