History

Fact Explanation
New or worsening dyspnea Obstruction of pulmonary arterial system by an embolus will lead to hemodynamic disturbances causing ventilation-perfusion mismatch eventually resulting respiratory insufficiency. Sometimes massive pulmonary emboli can cause acute right ventricular failure. Worsening of pre-existing dyspnoea may be the only symptom indicative of pulmonary embolism, in known patients with heart failure or pulmonary disease.[1,2,3,4]
Chest pain - substernal or pleuritic Substernal or pleuritic type chest pain is one of the most frequently found symptom of pulmonary embolism. This pain is due to pulmonary infarctions caused by distal emboli, causing irritation of the pleural surfaces.[1,2,3,4]
History of predisposing event or disease condition There are several factors recognized as predisposing factors for the development of pulmonary embolism. These factors are age of the patient, history of previous venous thromboembolism, history of active cancer, presence of a neurological disease with extremity paresis, medical disorders causing prolonged bed rest (heart or acute respiratory failure) and congenital or acquired thrombophilia including hormone replacement therapy and oral contraceptive therapy.[1,2,3,4]
Presence of symptoms suggestive of deep vein thrombosis:- unilateral leg swelling, pain, warmth, redness Pulmonary embolism and deep vein thrombosis share the same predisposing factors and in most cases, pulmonary embolism is a consequence of deep vein thrombosis. [1,2,3,4]
Fever Some patients with pulmonary embolism can present with low grade fever.[1,4]
Hemoptysis Pulmonary infarctions with associated alveolar hemorrhages produce coughing of blood.[1,3,4]
Sudden death, sudden collapse, syncope Massive pulmonary emboli might suddenly increase pulmonary vascular resistance to a level of afterload which cannot be matched by the right ventricle. Sudden death is also a possibilty, usually in the form of electromechanical dissociation. Otherwise, the patient presents with syncope indicating a severely reduced haemodynamic reserve, which might progress to shock and death due to acute right ventricular failure. [1,3,4]
References
  1. WILBUR J, SHIAN B. Diagnosis of deep venous thrombosis and pulmonary embolism. Am Fam Physician [online] 2012 Nov 15, 86(10):913-9 [viewed 29 June 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/23157144
  2. BARAIS MARIE, MORIO NATHALIE, CUZON BRETON AMéLIE, BARRAINE PIERRE, CALVEZ AMéLIE, STOLPER ERIK, VAN ROYEN PAUL, LIéTARD CLAIRE, MULVENNA JASON. “I Can't Find Anything Wrong: It Must Be a Pulmonary Embolism”: Diagnosing Suspected Pulmonary Embolism in Primary Care, a Qualitative Study. PLoS ONE [online] 2014 May [viewed 29 June 2014] Available from: doi:10.1371/journal.pone.0098112
  3. EBELL MH. Suspected pulmonary embolism: part I. Evidence-based clinical assessment. Am Fam Physician [online] 2004 Jan 15, 69(2):367-9 [viewed 29 June 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/14765779
  4. TORBICKI A., PERRIER A., KONSTANTINIDES S., AGNELLI G., GALIE N., PRUSZCZYK P., BENGEL F., BRADY A. J.B., FERREIRA D., JANSSENS U., KLEPETKO W., MAYER E., REMY-JARDIN M., BASSAND J.-P., VAHANIAN A., CAMM J., DE CATERINA R., DEAN V., DICKSTEIN K., FILIPPATOS G., FUNCK-BRENTANO C., HELLEMANS I., KRISTENSEN S. D., MCGREGOR K., SECHTEM U., SILBER S., TENDERA M., WIDIMSKY P., ZAMORANO J. L., ZAMORANO J.-L., ANDREOTTI F., ASCHERMAN M., ATHANASSOPOULOS G., DE SUTTER J., FITZMAURICE D., FORSTER T., HERAS M., JONDEAU G., KJELDSEN K., KNUUTI J., LANG I., LENZEN M., LOPEZ-SENDON J., NIHOYANNOPOULOS P., PEREZ ISLA L., SCHWEHR U., TORRACA L., VACHIERY J.-L.. Guidelines on the diagnosis and management of acute pulmonary embolism: The Task Force for the Diagnosis and Management of Acute Pulmonary Embolism of the European Society of Cardiology (ESC). European Heart Journal [online] 2008 March, 29(18):2276-2315 [viewed 29 June 2014] Available from: doi:10.1093/eurheartj/ehn310

Examination

Fact Explanation
Tachypnoea (≥20/minute) Ventilation - perfusion mismatch caused by the pulmonary embolus/emboli will cause increased respiratory rate to overcome the hypoxia.[1,2,3]
Tachycardia (>100/minute) Due to activation of the sympathetic system.[1,2,3]
Increased body temperature (>38.5°C) Found only in some patients.[1,3]
Signs of deep vein thrombosis - unilateral leg tenderness, redness, warmth, edema Since most of the time, pulmonary embolism is a consequence of deep vein thrombosis, signs of deep vein thrombosis should be assessed.[1,2,3]
Cyanosis Severe hypoxemia due to ventilation - perfusion mismatch can cause cyanosis.[3]
Hypotension In the most severe cases arterial hypotension may be present.[1,3]
Elevated jugular venous pressure Some patients will develop right ventricular dysfunction causing elevation of the jugular venous pressure.[3]
Stony dull areas of lung to percussion with absent breath sounds Sometimes pulmonary embolism is associated with pleural effusions due to pulmonary infarctions.[1,3]
References
  1. WILBUR J, SHIAN B. Diagnosis of deep venous thrombosis and pulmonary embolism. Am Fam Physician [online] 2012 Nov 15, 86(10):913-9 [viewed 29 June 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/23157144
  2. BARAIS MARIE, MORIO NATHALIE, CUZON BRETON AMéLIE, BARRAINE PIERRE, CALVEZ AMéLIE, STOLPER ERIK, VAN ROYEN PAUL, LIéTARD CLAIRE, MULVENNA JASON. “I Can't Find Anything Wrong: It Must Be a Pulmonary Embolism”: Diagnosing Suspected Pulmonary Embolism in Primary Care, a Qualitative Study. PLoS ONE [online] 2014 May [viewed 29 June 2014] Available from: doi:10.1371/journal.pone.0098112
  3. TORBICKI A., PERRIER A., KONSTANTINIDES S., AGNELLI G., GALIE N., PRUSZCZYK P., BENGEL F., BRADY A. J.B., FERREIRA D., JANSSENS U., KLEPETKO W., MAYER E., REMY-JARDIN M., BASSAND J.-P., VAHANIAN A., CAMM J., DE CATERINA R., DEAN V., DICKSTEIN K., FILIPPATOS G., FUNCK-BRENTANO C., HELLEMANS I., KRISTENSEN S. D., MCGREGOR K., SECHTEM U., SILBER S., TENDERA M., WIDIMSKY P., ZAMORANO J. L., ZAMORANO J.-L., ANDREOTTI F., ASCHERMAN M., ATHANASSOPOULOS G., DE SUTTER J., FITZMAURICE D., FORSTER T., HERAS M., JONDEAU G., KJELDSEN K., KNUUTI J., LANG I., LENZEN M., LOPEZ-SENDON J., NIHOYANNOPOULOS P., PEREZ ISLA L., SCHWEHR U., TORRACA L., VACHIERY J.-L.. Guidelines on the diagnosis and management of acute pulmonary embolism: The Task Force for the Diagnosis and Management of Acute Pulmonary Embolism of the European Society of Cardiology (ESC). European Heart Journal [online] 2008 March, 29(18):2276-2315 [viewed 29 June 2014] Available from: doi:10.1093/eurheartj/ehn310

Differential Diagnoses

Fact Explanation
Pleuritis In pleuritis, there will not be a history suggestive of predisposing factors for development of pulmonary embolism. Pleuritic chest pain will be prominent.[1]
Pericarditis and tamponade Characteristic chest pain, which is relieved with bending forwards and get worsened by lying down help differentiating pericarditis from pulmonary embolism. Echocardiography will help excluding cardiac tamponade.[1]
Acute coronary syndrome Ischemic type chest pain with typical ECG changes point towards acute coronary syndrome.[1,2,3]
Congestive heart failure and pulmonary edema Consider in patients with long term history of pre-existing heart failure. If there is worsening of the usual dyspnea, further investigation will be necessary for the diagnosis.[1,3]
Pneumothorax Clinical examination and the chest X-ray will aid the diagnosis.[1,2]
Aortic dissection Should consider in patients present with tearing substernal chest pain, sudden hemodynamic instability.[1,2,3]
References
  1. WILBUR J, SHIAN B. Diagnosis of deep venous thrombosis and pulmonary embolism. Am Fam Physician [online] 2012 Nov 15, 86(10):913-9 [viewed 29 June 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/23157144
  2. BARAIS MARIE, MORIO NATHALIE, CUZON BRETON AMéLIE, BARRAINE PIERRE, CALVEZ AMéLIE, STOLPER ERIK, VAN ROYEN PAUL, LIéTARD CLAIRE, MULVENNA JASON. “I Can't Find Anything Wrong: It Must Be a Pulmonary Embolism”: Diagnosing Suspected Pulmonary Embolism in Primary Care, a Qualitative Study. PLoS ONE [online] 2014 May [viewed 29 June 2014] Available from: doi:10.1371/journal.pone.0098112
  3. TORBICKI A., PERRIER A., KONSTANTINIDES S., AGNELLI G., GALIE N., PRUSZCZYK P., BENGEL F., BRADY A. J.B., FERREIRA D., JANSSENS U., KLEPETKO W., MAYER E., REMY-JARDIN M., BASSAND J.-P., VAHANIAN A., CAMM J., DE CATERINA R., DEAN V., DICKSTEIN K., FILIPPATOS G., FUNCK-BRENTANO C., HELLEMANS I., KRISTENSEN S. D., MCGREGOR K., SECHTEM U., SILBER S., TENDERA M., WIDIMSKY P., ZAMORANO J. L., ZAMORANO J.-L., ANDREOTTI F., ASCHERMAN M., ATHANASSOPOULOS G., DE SUTTER J., FITZMAURICE D., FORSTER T., HERAS M., JONDEAU G., KJELDSEN K., KNUUTI J., LANG I., LENZEN M., LOPEZ-SENDON J., NIHOYANNOPOULOS P., PEREZ ISLA L., SCHWEHR U., TORRACA L., VACHIERY J.-L.. Guidelines on the diagnosis and management of acute pulmonary embolism: The Task Force for the Diagnosis and Management of Acute Pulmonary Embolism of the European Society of Cardiology (ESC). European Heart Journal [online] 2008 March, 29(18):2276-2315 [viewed 29 June 2014] Available from: doi:10.1093/eurheartj/ehn310

Investigations - for Diagnosis

Fact Explanation
Electrocardiogram (ECG) Changes occur due to strain on the right ventricle and they are neither sensitive nor specific for pulmonary embolism. These ECG changes include inversion of T waves in leads V1–V4, a QR pattern in lead V1, the well known but uncommon S1Q3T3 pattern and incomplete or complete right bundle-branch block.[1,2]
Chest X-ray Chest X-ray should be done as a baseline investigation to exclude other causes of dyspnea and chest pain. Most frequent non specific findings associated with pulmonary embolism are plate-like atelectasis, pleural effusion and elevation of a hemidiaphragm.[1,2]
Arterial blood gas analysis (ABG) Pulmonary embolism is generally associated with hypoxaemia due to ventilation-perfusion mismatch, but up to 20% of patients will have normal oxygenation.[2]
Plasma D-dimer level Plasma D-dimer is a degradation product of crosslinked fibrin. Elevated levels can be found in plasma in the presence of an acute clot because of the activation of coagulation and fibrinolysis. The negative predictive value of D-dimer is high, so a normal D-dimer level indicates acute pulmonary embolism unlikely. Although D-dimer is very specific for fibrin, the specificity of fibrin for venous thromboembolism is poor because fibrin is produced in a wide variety of conditions and the positive predictive value of D-dimer is low. Therefore, D-dimer is not useful for confirming pulmonary embolism.[1,2]
Compression ultrasonography and computed tomographic venography Pulmonary embolism originates from deep vein thrombosis in a lower limb, in 90% of patients. Therefore it is important to detect deep vein thrombosis and for that lower limb compression venous ultrasonography and computed tomographic venography are the investigations of choice.[1,2]
Ventilation–perfusion scintigraphy (V/Q scan) The underlying basic principle of the test is based on an intravenous injection of technetium (Tc)-99 m labelled macroaggregated albumin particles, which block a small fraction of pulmonary capillaries and thereby enable scintigraphic assessment of lung perfusion at the tissue level. Where there is occlusion of pulmonary arterial branches, the peripheral capillary bed will not receive particles, rendering the area ‘cold’ on subsequent images. Perfusion scans are combined with ventilation studies, for which multiple tracers, such as xenon (Xe)-133 gas, Tc-99 m labelled aerosols or Tc-99 m-labelled carbon microparticles (Technegas), can be used. The purpose of the additional ventilation scan is to increase specificity by the identification of hypoventilation as a non-embolic cause of hypoperfusion due to reactive vasoconstriction (perfusion–ventilation match). On the contrary, in the case of pulmonary embolism, ventilation is expected to be normal in hypoperfused segments (perfusion–ventilation mismatch).[1,2]
CT (computed tomography) angiography With the introduction of multidetector computed tomography with high spatial and temporal resolution and quality of arterial opacification, CT angiography has become the investigation of choice for suspected pulmonary embolism. It visualizes the pulmonary arteries up to at least the segmental level adequately.[1,2]
Pulmonary angiography Eventhough pulmonary angiography is a reliable investigation, should be carried out only when the results of non-invasive imaging are equivocal. Whenever angiography is performed, direct haemodynamic measurements should be performed. The diagnostic criteria for acute pulmonary embolism in direct angiography consist of direct evidence of a thrombus, either a filling defect or amputation of a pulmonary arterial branch. With direct angiography, thrombi as small as 1 or 2 mm within the subsegmental arteries can be visualized. However, there is substantial interobserver variability at the subsegmental level. Other indirect signs include the presence of a slow flow of contrast, regional hypoperfusion and delayed or diminished pulmonary venous flow, but these are not validated and hence not diagnostic.[1]
Echocardiography In pulmonary embolism, 2D echocardiography will show right ventricular dilatation, tricuspid valve insufficiency which are useful in risk stratification. Transoesophageal echocardiography may detect thrombi in the pulmonary arteries. Echocardiography may also help ruling out differential diagnosis of the cause of shock, by detecting cardiac tamponade, acute valvular dysfunction, acute myocardial infarction or hypovolaemia.[1]
Brain natriuretic peptide (BNP) level Ventricular dysfunction is associated with increased myocardial stretch which leads to the myocardial injury and release of BNP. In acute pulmonary embolism, BNP levels reflect the severity of right ventricular dysfunction and haemodynamic compromise.[1]
Cardiac troponins Right ventricular infarctions has been found in autopsies of patients who died of massive pulmonary embolism. Elevated plasma troponin levels associated with worse prognosis in patients with pulmonary embolism.[1]
Heart-type fatty acid binding protein (H-FABP) level H-FABP is a newer and an early marker of myocardial injury. Documented to be superior to troponin or myoglobin measurements for risk stratification of pulmonary embolism on admission.[1]
References
  1. TORBICKI A., PERRIER A., KONSTANTINIDES S., AGNELLI G., GALIE N., PRUSZCZYK P., BENGEL F., BRADY A. J.B., FERREIRA D., JANSSENS U., KLEPETKO W., MAYER E., REMY-JARDIN M., BASSAND J.-P., VAHANIAN A., CAMM J., DE CATERINA R., DEAN V., DICKSTEIN K., FILIPPATOS G., FUNCK-BRENTANO C., HELLEMANS I., KRISTENSEN S. D., MCGREGOR K., SECHTEM U., SILBER S., TENDERA M., WIDIMSKY P., ZAMORANO J. L., ZAMORANO J.-L., ANDREOTTI F., ASCHERMAN M., ATHANASSOPOULOS G., DE SUTTER J., FITZMAURICE D., FORSTER T., HERAS M., JONDEAU G., KJELDSEN K., KNUUTI J., LANG I., LENZEN M., LOPEZ-SENDON J., NIHOYANNOPOULOS P., PEREZ ISLA L., SCHWEHR U., TORRACA L., VACHIERY J.-L.. Guidelines on the diagnosis and management of acute pulmonary embolism: The Task Force for the Diagnosis and Management of Acute Pulmonary Embolism of the European Society of Cardiology (ESC). European Heart Journal [online] 2008 March, 29(18):2276-2315 [viewed 29 June 2014] Available from: doi:10.1093/eurheartj/ehn310
  2. WILBUR J, SHIAN B. Diagnosis of deep venous thrombosis and pulmonary embolism. Am Fam Physician [online] 2012 Nov 15, 86(10):913-9 [viewed 29 June 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/23157144

Management - Specific Treatments

Fact Explanation
Haemodynamic support Essential in patients with suspected or confirmed pulmonary embolism presenting with shock or hypotension. Fluid management - Modest fluid challenge may help increase cardiac output in patients with pulmonary embolism, low cardiac output and normal blood pressure. Aggressive volume expansion may worsen RV function by causing mechanical overstretch and/or by reflex mechanisms that depress contractility. Use of inotropes - Norepinephrine improves right ventricular function via a direct positive inotropic effect while also improving right ventricular coronary perfusion by peripheral vascular alpha receptor stimulation and the increase in systemic blood pressure. Dobutamine raises cardiac output and improves oxygen transport and tissue oxygenation at a constant arterial PO2. Epinephrine also beneficial in patients with pulmonary embolism and shock. Nitric oxide inhalation may improve the haemodynamic status and gas exchange in patients with pulmonary embolism.[1,3]
Respiratory support Hypoxaemia is usually managed with nasal oxygen. Mechanical ventilation is rarely necessary. Measures should be taken to reduce oxygen consumption, such as reducing fever and agitation, and by instituting mechanical ventilation if the work of breathing is excessive. When mechanical ventilation is required, care should be taken to limit its adverse haemodynamic effects. In particular, positive intrathoracic pressure induced by mechanical ventilation may reduce venous return and worsen right ventricular failure in patients with massive pulmonary embolism. Therefore, positive end-expiratory pressure should be applied with caution. Low tidal volumes (approximately 6 ml/kg lean body weight) should be used in an attempt to keep the end-inspiratory plateau pressure below 30 cm H2O.[3]
Thrombolysis Thrombolytic therapy is the treatment of choice for the patients with high-risk pulmonary embolism, as it rapidly resolves thromboembolic obstruction and give rise to beneficial effects on haemodynamic parameters. Routine use of thrombolysis in non-high-risk patients is not recommended, but may be considered in selected patients with intermediate-risk. Thrombolytic regimens for pulmonary embolism can be used as follows:- 1) Streptokinase - 250 000 IU as a loading dose over 30 min, followed by 100 000 IU/h over 12–24 h (Accelerated regimen: 1.5 million IU over 2 h) 2) Urokinase - 4400 IU/kg as a loading dose over 10 min, followed by 4400 IU/kg/h over 12–24 h (Accelerated regimen: 3 million IU over 2 h) 3) rtPA (recombinant tissue plasminogen activator) - 100 mg over 2 h or 0.6 mg/kg over 15 min (maximum dose 50 mg) Thrombolytic therapy carries a significant risk of bleeding. Absolute contraindications include haemorrhagic stroke or stroke of unknown origin at any time, ischaemic stroke in preceding 6 months, central nervous system damage or neoplasms, recent major trauma/surgery/head injury (within preceding 3 weeks), gastrointestinal bleeding within the last month and known bleeding.[1,2,3]
Anticoagulation 1) Initial anticoagulation - To achieve rapid anticoagulation parenteral anticoagulants, such as intravenous unfractionated heparin (80 U/kg as a bolus injection followed by infusion at the rate of 18 U/kg/h), subcutaneous low-molecular-weight heparin (LMWH) or subcutaneous fondaparinux should be used. Subsequent doses of unfractionated heparin should be adjusted using an activated partial thromboplastin time (aPTT). 2) Long term anticoagulation - To prevent recurrent venous thromboembolic events. Vitamin K antagonists are used in majority of patients with a target INR of 2.5 (range 2.0–3.0), while low molecular weight heparin may be an effective alternative in cancer patients. Duration of treatment should be individualized according to their risk category of pulmonary embolism.[1,2,3]
Surgical pulmonary embolectomy Pulmonary embolectomy is a valuable therapeutic option in patients with high-risk pulmonary embolism in whom thrombolysis is absolutely contraindicated or has failed.[1,3]
Percutaneous catheter embolectomy and fragmentation Considered as an alternative treatment option in high-risk patients with pulmonary embolism, when thrombolysis is absolutely contraindicated or has failed. Complications of these procedures include local damage to the puncture site, perforation of cardiac structures, tamponade and contrast reactions.[1,3]
Venous filters Systematic use of venous filters is not recommended. May be used when there are absolute contraindications to anticoagulation and a high risk of venous thromboembolism recurrence. Considered in pregnant women who develop extensive thrombosis in the weeks before delivery. As soon as it is safe to use anticoagulants, retrievable filters should be removed. Filters are usually placed in the infrarenal portion of the inferior vena cava (IVC). If thrombus is identified in the IVC below the renal veins, more superior placement may be indicated. Permanent IVC filters may provide lifelong protection against pulmonary embolism. However, they are associated with complications and late sequelae, including recurrent deep vein thrombosis and development of the post-thrombotic syndrome.[3]
Special considerations - during pregnancy The risk of pulmonary embolism is higher in the postpartum period, particularly after a caesarean section. The treatment is based mainly on heparin (unfractionated or low molecular weight heparin). The heparin treatment should be given throughout the entire pregnancy. [3]
Non-thrombotic pulmonary embolism management Nonthrombotic pulmonary embolism is due to a variety of embolic materials (septic emboli, intravascular foreign bodies, fat, air, amniotic fluid, tumour emboli). Usually the haemodynamic consequences of non-thrombotic emboli are usually mild. Treatment is mostly supportive but may differ according to the type of embolic material and clinical severity.[3]
References
  1. JAFF M. R., MCMURTRY M. S., ARCHER S. L., CUSHMAN M., GOLDENBERG N., GOLDHABER S. Z., JENKINS J. S., KLINE J. A., MICHAELS A. D., THISTLETHWAITE P., VEDANTHAM S., WHITE R. J., ZIERLER B. K.. Management of Massive and Submassive Pulmonary Embolism, Iliofemoral Deep Vein Thrombosis, and Chronic Thromboembolic Pulmonary Hypertension: A Scientific Statement From the American Heart Association. Circulation [online] December, 123(16):1788-1830 [viewed 29 June 2014] Available from: doi:10.1161/​CIR.0b013e318214914f
  2. RAMZI DW, LEEPER KV. DVT and pulmonary embolism: Part II. Treatment and prevention. Am Fam Physician [online] 2004 Jun 15, 69(12):2841-8 [viewed 29 June 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/15222649
  3. TORBICKI A., PERRIER A., KONSTANTINIDES S., AGNELLI G., GALIE N., PRUSZCZYK P., BENGEL F., BRADY A. J.B., FERREIRA D., JANSSENS U., KLEPETKO W., MAYER E., REMY-JARDIN M., BASSAND J.-P., VAHANIAN A., CAMM J., DE CATERINA R., DEAN V., DICKSTEIN K., FILIPPATOS G., FUNCK-BRENTANO C., HELLEMANS I., KRISTENSEN S. D., MCGREGOR K., SECHTEM U., SILBER S., TENDERA M., WIDIMSKY P., ZAMORANO J. L., ZAMORANO J.-L., ANDREOTTI F., ASCHERMAN M., ATHANASSOPOULOS G., DE SUTTER J., FITZMAURICE D., FORSTER T., HERAS M., JONDEAU G., KJELDSEN K., KNUUTI J., LANG I., LENZEN M., LOPEZ-SENDON J., NIHOYANNOPOULOS P., PEREZ ISLA L., SCHWEHR U., TORRACA L., VACHIERY J.-L.. Guidelines on the diagnosis and management of acute pulmonary embolism: The Task Force for the Diagnosis and Management of Acute Pulmonary Embolism of the European Society of Cardiology (ESC). European Heart Journal [online] 2008 March, 29(18):2276-2315 [viewed 29 June 2014] Available from: doi:10.1093/eurheartj/ehn310