Pulmonary embolism (TELA)

Pulmonary embolism (PE) is the occlusion of one or more pulmonary arteries by blood clots that form elsewhere, usually in the large veins of the legs or pelvis.

Risk factors include conditions that impair venous return and cause endothelial injury or dysfunction, particularly in patients with hypercoagulable states. Symptoms of pulmonary embolism (PE) include dyspnea, pleuritic chest pain, cough, and, in severe cases, syncope or cardiac and respiratory arrest. Findings are vague and may include tachypnea, tachycardia, hypotension, and increased pulmonary component of the second heart sound. Diagnosis is based on ventilation/perfusion scanning, CT angiography, or pulmonary arteriography. Treatment of pulmonary embolism (PE) includes anticoagulants, thrombolytics, and sometimes surgery to remove the clot.

Pulmonary embolism (PE) occurs in approximately 650,000 people and causes up to 200,000 deaths per year, accounting for approximately 15% of all hospital deaths per year. The incidence of pulmonary embolism (PE) in children is approximately 5 per 10,000 admissions.

Causes of pulmonary embolism

Almost all pulmonary emboli result from thrombosis in the lower extremities or pelvic veins (deep venous thrombosis [DVT]). Thrombi in either system may be silent. Thromboemboli may also occur in the veins of the upper extremities or in the right side of the heart. Risk factors for deep venous thrombosis and pulmonary embolism (PE) are the same in children and adults and include conditions that impair venous return or cause endothelial injury or dysfunction, particularly in patients with an underlying hypercoagulable state. Bed rest and limitation of ambulation, even for a few hours, are common precipitating factors.

Once deep vein thrombosis develops, the thrombus may break off and travel through the venous system to the right side of the heart, then lodge in the pulmonary arteries, where it partially or completely blocks one or more vessels. The consequences depend on the size and number of emboli, the response of the lungs, and the ability of the person's internal thrombolytic system to dissolve the thrombus.

Small emboli may have no acute physiologic effects; many begin to lyse immediately and resolve within hours to days. Large emboli may cause a reflex increase in ventilation (tachypnea); hypoxemia due to ventilation/perfusion (V/Q) mismatch and shunting; atelectasis due to alveolar hypocapnia and surfactant defects; and an increase in pulmonary vascular resistance caused by mechanical obstruction and vasoconstriction. Endogenous lysis resolves most emboli, even those of considerable size, without treatment, and the physiologic responses subside within hours to days. Some emboli are resistant to lysis and may organize and persist. Occasionally, chronic residual obstruction results in pulmonary hypertension (chronic thromboembolic pulmonary hypertension), which may develop over years and lead to chronic right ventricular failure. When large emboli occlude major arteries or when many small emboli occlude more than 50% of the distal arteries of the system, right ventricular pressure increases, causing acute right ventricular failure, failure with shock (massive pulmonary embolism (PE)) or sudden death in severe cases. The risk of death depends on the degree and frequency of right heart pressure increases and on the patient's prior cardiopulmonary status; higher pressures are more common in patients with preexisting heart disease. Healthy patients can survive pulmonary embolism that occludes more than 50% of the pulmonary vascular bed.

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Risk factors for deep vein thrombosis and pulmonary embolism (PE)

• Age > 60 years
• Atrial fibrillation
• Cigarette smoking (including passive smoking)
• Estrogen receptor modulators (raloxifene, tamoxifen)
• Limb injuries
• Heart failure
• Hypercoagulable states
• Antiphospholipid syndrome
• Antithrombin III deficiency
• Factor V Leiden mutation (activated protein C resistance)
• Heparin-induced thrombocytopenia and thrombosis
• Hereditary defects of fibrinolysis
• Hyperhomocysteinemia
• Increase in factor VIII
• Increase in factor XI
• Increased von Willebrand factor
• Paroxysmal nocturnal hemoglobinuria
• Protein C deficiency
• Protein S deficiency
• Genetic defects of prothrombin GA
• Tissue factor pathway inhibitor
• Immobilization
• Insertion of venous catheters
• Malignant neoplasms
• Myeloproliferative diseases (hyperviscosity)
• Nephrotic syndrome
• Obesity
• Oral contraceptives/estrogen replacement therapy
• Pregnancy and postpartum period
• Previous venous thromboembolism
• Sickle cell anemia
• Surgery in the previous 3 months

Pulmonary infarction occurs in less than 10% of patients diagnosed with pulmonary embolism (PE). This low percentage is attributed to the dual blood supply to the lungs (i.e., bronchial and pulmonary). Infarction is typically characterized by a radiographic infiltrate, chest pain, fever, and sometimes hemoptysis.

Nonthrombotic pulmonary embolism (PE)

Pulmonary embolism (PE), arising from a variety of nonthrombotic sources, causes clinical syndromes that differ from thrombotic pulmonary embolism (PE).

Air embolism occurs when a large volume of air is injected into the systemic veins or right heart, which then moves into the pulmonary arterial system. Causes include surgery, blunt or barotrauma (eg, during mechanical ventilation), use of defective or uncapped venous catheters, and rapid decompression after underwater diving. Microbubble formation in the pulmonary circulation can cause endothelial injury, hypoxemia, and diffuse infiltration. Large-volume air embolism can cause pulmonary outflow tract obstruction, which can be rapidly fatal.

Fat embolism is caused by the entry of fat or bone marrow particles into the systemic venous circulation and then into the pulmonary arteries. Causes include long bone fractures, orthopedic procedures, capillary occlusion or necrosis of bone marrow in patients with sickle cell crisis, and, rarely, toxic modification of native or parenteral serum lipids. Fat embolism causes a pulmonary syndrome similar to acute respiratory distress syndrome, with severe hypoxemia of rapid onset, often accompanied by neurologic changes and a petechial rash.

Amniotic fluid embolism is a rare syndrome caused by amniotic fluid entering the maternal venous circulation and then into the pulmonary arterial system during or after delivery. The syndrome may occasionally occur with antenatal uterine manipulation. Patients may present with cardiac shock and respiratory distress due to anaphylaxis, vasoconstriction causing acute severe pulmonary hypertension, and direct pulmonary capillary injury.

Septic embolism occurs when infected material enters the lungs. Causes include drug use, right-sided infective endocarditis, and septic thrombophlebitis. Septic embolism causes symptoms and signs of pneumonia or sepsis and is initially diagnosed by finding focal infiltrates on chest radiography that may enlarge peripherally and form abscesses.

Foreign body embolism is caused by the introduction of particles into the pulmonary arterial system, usually due to the intravenous administration of inorganic substances such as talc by heroin addicts or mercury by patients with mental disorders.

Tumor embolism is a rare complication of malignancy (usually adenocarcinoma) in which tumor cells from a tumor enter the venous and pulmonary arterial systems, where they lodge, proliferate, and obstruct blood flow. Patients typically present with symptoms of dyspnea and pleuritic chest pain, as well as signs of cor pulmonale, that develop over weeks to months. The diagnosis, which is suspected in the presence of fine nodular or diffuse pulmonary infiltrates, can be confirmed by biopsy or sometimes by cytologic examination of aspirated fluid and histologic examination of pulmonary capillary blood.

Systemic gas embolism is a rare syndrome that occurs when barotrauma occurs during mechanical ventilation with high airway pressures, resulting in air leaking from the lung parenchyma into the pulmonary veins and then into the systemic arterial vessels. Gas emboli cause CNS lesions (including stroke), cardiac damage, and livedo reticularis in the shoulders or anterior chest wall. Diagnosis is based on exclusion of other vascular processes in the presence of established barotrauma.

Symptoms of pulmonary embolism

Most pulmonary emboli are small, physiologically insignificant, and asymptomatic. Even when they occur, symptoms of pulmonary embolism (PE) are nonspecific and vary in frequency and intensity depending on the extent of pulmonary vascular occlusion and preexisting cardiopulmonary function.

Large emboli cause acute dyspnea and pleuritic chest pain and, less commonly, cough and/or hemoptysis. Massive pulmonary embolism (PE) causes hypotension, tachycardia, syncope, or cardiac arrest.

The most common symptoms of pulmonary embolism (PE) are tachycardia and tachypnea. Less commonly, patients have hypotension, a loud second heart sound (S2) due to increased pulmonary component (P), and/or crackles and wheezes. In the presence of right ventricular failure, there may be visible internal jugular venous distension and right ventricular heave, and a right ventricular gallop rhythm (third and fourth heart sounds [S3 and S4]), with or without tricuspid regurgitation, may be present. Fever may be present; deep vein thrombosis and pulmonary embolism (PE) are often excluded as causes of fever.

Chronic thromboembolic pulmonary hypertension causes symptoms and signs of right heart failure, including dyspnea on exertion, fatigue, and peripheral edema that develop over months to years.

Diagnosis of pulmonary embolism

The diagnosis is equivocal because symptoms and signs are nonspecific and diagnostic tests are either imperfect or invasive. The diagnosis begins with including pulmonary embolism (PE) in the differential diagnosis of a large number of conditions with similar symptoms, including cardiac ischemia, heart failure, exacerbation of COPD, pneumothorax, pneumonia, sepsis, acute chest syndrome (in patients with sickle cell disease), and acute anxiety with hyperventilation. Initial workup should include pulse oximetry, ECG, and chest radiography. Chest radiography is usually nonspecific but may show atelectasis, focal infiltrates, a high-standing diaphragm, and/or pleural effusion. Classic findings include focal disappearance of the vascular component (Westermarck's sign), peripheral triangular infiltrate (Hampton's triangle), or dilation of the right descending pulmonary artery (Pall's sign), but these are suspicious but insensitive signs.

Pulse oximetry is a rapid way to assess oxygenation; one of the signs of pulmonary embolism (PE) is hypoxemia, but other significant abnormalities should also be investigated.

The ECG most often reveals tachycardia and variable ST-T changes that are nonspecific for pulmonary embolism (PE). An SQT sign or new right bundle branch block may indicate the effect of an acute increase in right ventricular pressure on right ventricular conduction; they are specific but insensitive, occurring in only about 5% of patients. Right axis deviation and P pulmonale may be present. T-wave inversion in leads 1–4 also occurs.

The clinical probability of pulmonary embolism (PE) can be estimated by correlating the ECG and chest radiography with the history and physical examination. Patients with a low clinical probability of pulmonary embolism (PE) may require only minimal or no further testing. Patients with an intermediate clinical probability require further testing. Patients with a high probability may be candidates for immediate treatment pending the results of further testing.

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Non-invasive diagnostics of pulmonary embolism

Noninvasive tests can usually be performed more quickly and have fewer complications than invasive tests. The most useful tests for diagnosing and ruling out pulmonary embolism (PE) are D-dimer tests, ventilation-perfusion scanning, duplex ultrasonography, helical CT, and echocardiography.

There is no universally accepted algorithm for the selection and sequence of tests, but general requirements include a D-dimer screening test and lower extremity ultrasonography. If D-dimer is positive and ultrasonography is negative for thrombus, CT or pulmonary embolism testing is performed next. Patients with moderate to high probability of pulmonary embolism (PE) based on clinical criteria but low or equivocal probability based on pulmonary embolism testing usually require pulmonary arteriography or helical CT to confirm or exclude the diagnosis. Positive lower extremity ultrasonography results establish the need for anticoagulation and eliminate the need for further diagnostic testing. Negative ultrasonography results do not eliminate the need for additional testing. A positive D-dimer, ECG, arterial blood gas measurements, chest x-ray, and echocardiogram are additional tests that are not specific enough to be considered diagnostic without other data.

D-dimer is a by-product of intrinsic fibrinolysis; thus, elevated levels suggest recent thrombus formation. The test is extremely sensitive; more than 90% of patients with DVT/PE have elevated levels. However, a positive result is not specific for venous thrombus, as levels are elevated in many patients without DVT/PE. In contrast, a low D-dimer has a negative predictive value of more than 90%, allowing the exclusion of deep vein thrombosis and pulmonary embolism, especially when the initial probability estimate is less than 50%. There are reported cases of pulmonary embolism (PE) in the presence of a negative D-dimer test using older enzyme-linked immunosorbent assays, but newer, highly specific, and rapid assays make a negative D-dimer a reliable test to exclude the diagnosis of PE in routine practice.

The V/P scan can detect areas of the lung that are ventilated but not perfused, which occurs in pulmonary embolism (PE); the results are graded as low, intermediate, or high probability of PE based on the V/P results. Completely normal scan results essentially rule out PE with almost 100% accuracy, but low probability results still retain a 15% chance of PE. Perfusion deficits can occur in many other conditions, including pleural effusion, chest tumors, pulmonary hypertension, pneumonia, and COPD.

Duplex scanning is a safe, non-traumatic, portable method for detecting thrombi in the lower extremities (primarily the femoral vein). A thrombus can be detected in three ways: by visualizing the vein outline, demonstrating non-compressibility of the vein, and identifying reduced flows during Doppler examination. The study has a sensitivity of over 90% and a specificity of over 95% for thrombosis. The method does not reliably detect thrombi in the veins of the calf or iliac veins. The absence of thrombi in the femoral veins does not exclude the possibility of thrombosis in other locations, but patients with negative duplex ultrasonography results have a survival rate of over 95% without developing cases of pulmonary embolism (PE), since thrombi from other sources are much less common. Ultrasonography has been included in many diagnostic algorithms because findings of femoral vein thrombosis indicate the need for anticoagulant therapy, which may make further investigations for pulmonary embolism or other thromboses unnecessary.

Helical CT with contrast is an alternative to VP scanning and pulmonary arteriography in many cases because it is rapid, affordable, and noninvasive and provides more information about other lung pathology. However, the patient must be able to hold his breath for several seconds. The sensitivity of CT is highest for pulmonary embolism (PE) in lobar and segmental vessels and lowest for emboli in small subsegmental vessels (approximately 30% of all PEs) and is thus generally less sensitive than perfusion scanning (60% vs. >99%). It is also less specific than pulmonary arteriograms (90% vs. >95%) because imaging findings may arise from incomplete mixing of the contrast. Positive scans may be diagnostic of pulmonary embolism (PE), but negative scans do not necessarily exclude subsegmental disease, although the clinical significance of embolism in small subsegmental vessels requires clarification. New scanners with higher resolution are likely to improve diagnostic accuracy and thus may replace perfusion scanning and arteriograms.

The usefulness of echocardiography as a diagnostic test for pulmonary embolism (PE) is controversial. It has a sensitivity of >80% for detecting right ventricular dysfunction (eg, dilation and hypokinesis, which occurs when pulmonary artery pressure exceeds 40 mmHg). It is a useful test for determining the severity of hemodynamic compromise in acute PE, but right ventricular dysfunction is present in many conditions, including COPD, heart failure, and sleep apnea, and is therefore a nonspecific test. Assessment of pulmonary artery systolic pressure, using Doppler flow studies, provides additional useful information about the severity of acute PE. The absence of right ventricular dysfunction or pulmonary hypertension makes the diagnosis of major PE unlikely but does not exclude it.

Cardiac markers are considered useful in mortality risk stratification in patients with acute pulmonary embolism (PE). Elevated troponin levels may indicate right ventricular injury. Elevated brain natriuretic peptide (BNP) and npo-BNP levels are not diagnostic, but low levels probably reflect a good prognosis. The clinical significance of these tests should be determined, as they are not specific for either right ventricular distension or PE.

Arterial blood gas and exhaled air PaCO2 measurements provide an estimate of the physiological dead space (i.e., the fraction of the lung that is ventilated but not perfused). When the dead space is less than 15% and the D-dimer level is low, the negative predictive value for acute pulmonary embolism (PE) is 98%.

Invasive diagnostics of pulmonary embolism

Pulmonary angiography is indicated when the probability of pulmonary embolism (PE) based on previous studies is moderate to high and noninvasive tests are inconclusive; when there is an urgent need to confirm or exclude the diagnosis, such as in an acutely ill patient; and when anticoagulant therapy is contraindicated.

Pulmonary arteriography remains the most accurate test for diagnosing pulmonary embolism (PE), but is much less frequently needed because of the sensitivity of ultrasonography and helical CT. An arteriogram with intraluminal filling defects or abrupt flow reduction is positive. Suspicious findings, but not diagnostic of PE, include partial occlusion of pulmonary arterial branches with increased proximal and decreased distal caliber, hypovolemic areas, and retention of contrast in the proximal artery during the late (venous) phase of the arteriogram. In lung segments with obstructed arteries, venous filling with contrast is delayed or absent.

Treatment of pulmonary embolism

Initial treatment of pulmonary embolism (PE) includes oxygen therapy to correct hypoxemia and intravenous 0.9% saline and vasopressors to treat hypotension. All patients with strongly suspected or confirmed pulmonary embolism (PE) should be hospitalized and, ideally, should be monitored for life-threatening cardiovascular complications in the first 24 to 48 hours. Subsequent treatment includes anticoagulation and sometimes clot removal.

Removal of a blood clot

Thrombus lysis or removal should be considered in patients with hypotension. It may also be considered in patients with clinical, ECG, and/or echocardiographic evidence of right ventricular overload or failure, but the data supporting this approach are not absolute. Thrombus elimination is achieved using embolectomy or intravenous thrombolytic therapy.

Embolectomy is indicated for patients with pulmonary embolism (PE) who are at risk of cardiac or respiratory arrest (persistent systolic blood pressure < 90 mmHg after fluid and O2 _therapy, or if vasopressor therapy is required). Suction or fragmentation of the embolus through a pulmonary artery catheter minimizes the morbidity of surgical embolectomy, but the benefit of this technique is unproven. Surgical embolectomy probably improves survival in patients with massive PE, but is not widely available and is associated with high mortality. The decision to perform embolectomy and the choice of technique depend on local capabilities and experience.

Thrombolytic therapy with tissue plasmagen activator (tPA), streptokinase, or urokinase offers a noninvasive way to rapidly restore pulmonary blood flow but is controversial because the long-term benefit does not significantly outweigh the risk of bleeding. Thrombolytics accelerate the resolution of radiographic changes and the recovery of hemodynamic functions (heart rate and right ventricular function) and prevent cardiopulmonary decompensation in patients with submassive pulmonary embolism (PE), but do not improve survival. Some authors recommend thrombolytics for normotensive patients with PE with echocardiographic evidence of proximal (large) pulmonary embolism or right ventricular dysfunction due to PE or preexisting disease. Others recommend thrombolytic therapy for patients with massive pulmonary embolism (PE) (hypotension, hypoxemia, or obstruction of 2 or more lobar arteries). Absolute contraindications to thrombolysis include prior hemorrhagic stroke; active bleeding from any source; intracranial trauma or surgery within 2 months; recent puncture of the femoral or other major artery; gastrointestinal bleeding including positive occult blood tests (< 6 months); and cardiopulmonary resuscitation. Relative contraindications include recent surgery (< 10 days), bleeding diathesis (eg, due to liver failure), pregnancy, and severe hypertension (systolic BP > 180 or diastolic BP > 110 mmHg).

Streptokinase, urokinase, and alteplase (recombinant tPA) can be used for thrombolysis. None of these drugs has demonstrated clear superiority over the others. Standard intravenous regimens are streptokinase 250,000 U over 30 min, then continuous infusion of 100,000 U/hour for 24 h; urokinase 4,400 U/kg over 10 min, continued at 4,400 U/kg/hour for 12 h; or alteplase 100 mg by continuous administration for more than 2 hours, followed by an additional administration of 40 mg for another 4 hours (10 mg/hour) or tenecteplase (the dose is calculated depending on body weight, the maximum dose should not exceed 10,000 IU 50 mg. The required dose of the drug is administered by a rapid single intravenous injection over 5-10 seconds). If clinical manifestations and repeated pulmonary angiograms indicate the absence of thrombus lysis and the initial doses do not cause bleeding. Streptokinase is now rarely used, since it often causes allergic and pyrogenic reactions and requires prolonged administration.

The initial infusion dose of heparin should be given simultaneously, but the activated PTT should be allowed to decline to 1.5-2.5 times the baseline level before initiating continuous infusion. Direct thrombolysis with thrombolytics administered through a pulmonary artery catheter is sometimes used in patients with massive pulmonary embolism (PE) or for patients with relative contraindications to systemic thrombolysis, but this approach does not prevent systemic thrombolysis. If bleeding occurs, it can be completely controlled with cryoprecipitate or fresh frozen plasma and compression of accessible vascular sites.

Anticoagulant therapy

Because venous thromboses rarely embolize completely, anticoagulation therapy is initiated urgently to prevent residual thrombus from enlarging and causing embolism. Patients in whom anticoagulants are contraindicated or in whom thromboembolism occurs despite therapeutic anticoagulation should undergo a percutaneous inferior vena cava filter procedure.

Heparin, either unfractionated or low molecular weight, is the mainstay of treatment for acute deep vein thrombosis and pulmonary embolism (PE) and should be given promptly at diagnosis, or as soon as possible if clinical suspicion is high; inadequate anticoagulation in the first 24 h is associated with an increased risk of recurrent pulmonary embolism within 3 months. Heparin accelerates the action of antithrombin-III, an inhibitor of clotting factors; unfractionated heparin also has antithrombin-III mediated anti-inflammatory properties that may promote thrombus organization and reduce thrombophlebitis. Unfractionated heparin is given by bolus and infusion according to protocol, achieving an activated PTT of 1.5-2.5 times that of normal controls. Subcutaneous low molecular weight heparin (LMWH) is as effective as unfractionated heparin and causes less thrombocytopenia. Its long half-life makes it suitable for outpatient treatment of patients with deep vein thrombosis and facilitates earlier discharge of patients who have not achieved therapeutic anticoagulation with warfarin.

All heparins may cause bleeding, thrombocytopenia, urticaria, and, rarely, thrombosis or anaphylaxis. Long-term use of heparin may cause hypokalemia, elevated liver enzymes, and osteoporosis. Patients should be screened for bleeding by repeated complete blood counts and fecal occult blood tests. Bleeding due to overheparinization can be controlled with a maximum of 50 mg protamine in 5000 U unfractionated heparin (or 1 mg in 20 mL normal saline infused over 10 to 20 minutes for LMWH, although the exact dose is uncertain because protamine only partially reverses LMWH's inactivation of Factor Xa). Heparin or LMWH treatment should be continued until complete anticoagulation is achieved with oral warfarin. The use of LMWH in long-term anticoagulation therapy after acute pulmonary embolism (PE) has not been studied but is likely to be limited by cost and complexity of administration compared with oral warfarin.

Warfarin is the oral drug of choice for long-term anticoagulation in all patients except pregnant women and patients with new or worsening venous thromboembolism during warfarin therapy. The drug is started at a dose of 5-10 mg as tablets once daily in the first 48 hours after the start of effective heparinization or, rarely, in patients with protein C deficiency, only after therapeutic hypocoagulation has been achieved. The therapeutic goal is usually an INR of 2-3.

Prescribers should be aware of multiple drug interactions, including interactions with over-the-counter herbal medicines. Patients with transient risk factors for deep vein thrombosis or pulmonary embolism (PE) (eg, fracture, surgery) may discontinue the drug after 3 to 6 months. Patients with non-transient risk factors (eg, hypercoagulability), no identified risk factors, or a history of recurrent deep vein thrombosis or pulmonary embolism should continue warfarin for at least 6 months and possibly for life if no complications of therapy develop. In low-risk patients, warfarin is given at low intensity (to maintain INR between 1.5 and 2.0) and may be safe and effective for at least 2 to 4 years, but this regimen requires further evidence of safety before it can be recommended. Bleeding is the most common complication of warfarin therapy; patients over 65 years of age and those with underlying medical conditions (especially diabetes mellitus, recent myocardial infarction, hematocrit <30%, creatinine >1.5 mg/dL) and a history of stroke or gastrointestinal bleeding are probably at greatest risk. Bleeding can be completely controlled by subcutaneous or oral administration of 2.5–10 mg vitamin K and, in severe cases, fresh frozen plasma. Vitamin K may cause sweating, local pain, and, rarely, anaphylaxis.

Placement of an inferior vena cava filter (IVC filter, IF) is indicated in patients with contraindications to anticoagulant therapy and thrombolysis, with recurrent emboli on adequate anticoagulation, or after pulmonary embolectomy. There are several types of filters, differing in size and replaceability. The filter is placed by catheterization of the internal jugular or femoral veins; the optimal location is just below the renal vein entry. Filters reduce acute and subacute thromboembolic complications but are associated with later complications; for example, venous collaterals may develop and provide a bypass route by which pulmonary embolism (PE) can bypass the filter. Patients with recurrent deep vein thrombosis or chronic risks for developing deep vein thrombosis may therefore still require anticoagulation; Filters provide some protection until contraindications to anticoagulation disappear. Despite widespread use of filters, their effectiveness in preventing pulmonary embolism (PE) has not been studied or proven.

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Prevention of pulmonary embolism

Pulmonary embolism (PE) prophylaxis means preventing deep vein thrombosis; the need depends on the patient's risk. Bedridden patients and patients undergoing surgery, especially orthopaedic, have the greatest need, and most of these patients should be identified before a clot forms. PE is prevented by low-dose unfractionated heparin (UFH), LMWH, warfarin, newer anticoagulants, compression devices and stockings.

The choice of drug or device depends on the duration of treatment, contraindications, relative costs, and ease of use.

NDNFG is given at a dose of 5000 units subcutaneously 2 hours before surgery and every 8-12 hours thereafter for 7-10 days or until the patient is completely ambulatory. Immobilized patients who are not undergoing surgery should receive 5000 units subcutaneously every 12 hours indefinitely or until the risk has disappeared.

The dosage of LMWH depends on the drug: enoxaparin 30 mg subcutaneously every 12 hours, dalteparin 2500 IU once daily, and tinzaparin 3500 IU once daily are just three of many equally effective LMWHs that are not inferior to NDNFH in terms of preventing deep vein thrombosis and pulmonary embolism (PE).

Warfarin is usually effective and safe at a dose of 2-5 mg once daily or at a dose adjusted to maintain the INR between 1.5 and 2.

Newer anticoagulants, including hirudin (a subcutaneous direct thrombin inhibitor), ximelagatran (an oral direct thrombin inhibitor), and danaparoid and fondaparinux, which are selective factor Xa inhibitors, have shown efficacy in deep vein thrombosis and pulmonary embolism (PE) prevention but require further study to determine their cost-effectiveness and safety relative to heparins and warfarin. Aspirin is more effective than placebo but less effective than all other available drugs in preventing deep vein thrombosis and pulmonary embolism (PE).

Intermittent pneumatic compression (IPC) delivers rhythmic external compression to the legs or from the legs to the thighs. It is more effective in preventing calf thrombosis than proximal deep vein thrombosis and is therefore considered ineffective after hip or knee surgery. IPC is contraindicated in obese patients and may theoretically cause pulmonary embolism in immobilized patients who have developed silent deep vein thrombosis or who have not received prophylactic treatment.

Graduated elastic stockings are of questionable effectiveness except in low-risk surgical patients. However, combining stockings with other preventive measures may be more effective than any one measure alone.

For surgeries with a high risk of VTE, such as orthopaedic hip and lower extremity surgery, NDFG and aspirin alone are not adequate; LMWH and titrated warfarin are recommended. In knee replacement, the risk reduction provided by LMWH and IPC is comparable; the combination is considered for patients with associated clinical risks. In orthopaedic surgery, the drugs can be started preoperatively and continued for at least 7 days postoperatively. In some patients with very high risk of both VTE and bleeding, intravenous CF is a prophylactic measure.

A high incidence of venous thromboembolism is also associated with some types of neurosurgical procedures, acute spinal cord injury, and polytrauma. Although physical methods (IPC, elastic stockings) have been used in neurosurgical patients due to concerns about intracranial hemorrhage, LMWH is probably an acceptable alternative. The combination of IPC and LMWH may be more effective than either method alone in high-risk patients. Limited data support the combination of IPC, elastic stockings, and LMWH in spinal cord injury or polytrauma. For very high-risk patients, CF placement may be considered.

The most common nonsurgical conditions in which deep vein thrombosis prophylaxis is indicated are myocardial infarction and ischemic stroke. In patients with myocardial infarction, NDNFH is effective. If anticoagulants are contraindicated, IPC, elastic stockings, or both may be used. In patients with stroke, NDNFH or LMWH may be used; IPC, elastic stockings, or both may be helpful.

Recommendations for some other nonsurgical conditions include NDNEF for patients with heart failure; titrated warfarin (INR 1.3-1.9) for patients with metastatic breast cancer; and warfarin 1 mg/day for cancer patients with a central venous catheter.

Forecast

Pulmonary embolism (PE) has a poor prognosis. Approximately 10% of patients with pulmonary embolism (PE) die within an hour. Of those who survive the first hour, only about 30% are diagnosed and treated; more than 95% of these patients survive. Thus, most fatal pulmonary embolism (PE) occurs in patients who are never diagnosed, and the best prospects for reducing mortality lie in improving diagnosis rather than treatment. Patients with chronic thromboembolic disease account for a very small proportion of PE survivors. Anticoagulant therapy reduces the recurrence rate of PE to approximately 5% in all patients.

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