INTRODUCTION — Acute pulmonary embolism (PE) is common and often fatal, with a mortality rate of approximately 30 percent without treatment [1-4]. Most deaths are due to recurrent PE within the first few hours of the initial event [5,6]. Therapy with anticoagulants decreases the mortality rate to 2 to 8 percent, making it imperative that effective therapy be instituted as quickly as possible [1,5,7-10].
The clinical severity of PE can be highly variable, ranging from asymptomatic to severe hypoxemia, right ventricular failure, shock, and death. As a result, therapy varies from patient to patient and requires considerable clinical judgment. Common questions asked by clinicians when a patient presents with PE include:
- Which anticoagulant should I administer? How much? How long?
- Should I administer thrombolytic therapy?
- Should an inferior vena caval filter be placed?
- Is embolectomy indicated?
- Can I withhold therapy and follow the patient instead?
Treatment of the patient with acute PE is reviewed here. More detailed discussions regarding anticoagulation and thrombolysis in PE are presented elsewhere. The epidemiology, prognosis, pathophysiology, risk factors, symptoms, signs, and diagnosis of PE are discussed separately. (See "Anticoagulation in acute pulmonary embolism" and "Fibrinolytic (thrombolytic) therapy in pulmonary embolism and deep vein thrombosis" and "Overview of acute pulmonary embolism" and "Diagnosis of acute pulmonary embolism".)
RESUSCITATION — When a patient presents with suspected PE, the initial focus is on stabilizing the patient.
Respiratory support — Supplemental oxygen should be administered if hypoxemia exists. Severe hypoxemia or respiratory failure should prompt consideration of intubation and mechanical ventilation. This must be performed carefully since patients with coexistent RV failure may be prone to hypotension following intubation. Initiation of mechanical ventilation is discussed separately. (See "Overview of mechanical ventilation", section on 'Initiation'.)
Hemodynamic support — Hemodynamic support should be instituted promptly when a patient presents with PE and hypotension, defined as a systolic blood pressure <90 mmHg or a drop in systolic blood pressure of ≥40 mmHg from baseline.
Intravenous fluid administration is first-line therapy. It may improve hemodynamic performance, as illustrated by a series of 13 patients with acute PE and a cardiac index (CI) < 2.5 L/min/m2 [11]. Administration of 500 mL of dextran significantly increased the CI from a mean of 1.6 to 2.0 L/min/m2.
Intravenous fluid (usually normal saline) should be administered cautiously because increased right ventricular (RV) wall stress can decrease the ratio of RV oxygen supply to demand. This may result in ischemia, deterioration of RV function, and worsening RV failure [12-16]. Clinicians should be wary of administering more than 500 to 1000 mL of normal saline during the initial resuscitation period [13]. If the patient's hypotension does not resolve with intravenous fluids, intravenous vasopressor therapy should promptly follow.
There are no randomized clinical trials that outline the optimal vasopressor for patients with shock due to PE:
- Either norepinephrine, dopamine, or epinephrine may be effective [14,15,17]. Norepinephrine is least likely to cause tachycardia, while dopamine is least expensive and often the most readily available.
- Dobutamine increases myocardial contractility and causes vasodilation (ie, decreases afterload), which is ideal for cardiogenic shock. However, the impact of vasodilation can exceed that of increased myocardial contractility, worsening the hypotension [18,19]. Combination therapy using dobutamine plus norepinephrine may permit increased myocardial contractility, while minimizing both vasodilation and the risk of hypotension.
- Isoproterenol, inamrinone, and milrinone have been investigated in animal models, but are not indicated for hypotension due to PE [20,21].
Physiologic properties and practical issues regarding the use of vasopressors are discussed separately. (See "Use of vasopressors and inotropes".)
Anticoagulation — Initiation of PE-directed therapy should be considered during the resuscitative period (algorithm 1). Empiric anticoagulant therapy is indicated when there is a high clinical suspicion of PE and no excess risk for bleeding. In this situation, we believe that the high mortality due to recurrent PE among patients who are untreated (approximately 30 percent) outweighs the risk of major bleeding (less than 3 percent) [1-4,22].
Anticoagulation prevents further clot formation, but does not lyse existing thromboemboli or decrease thrombus size. Thus, it should not be expected to affect mortality within the first hours of delivery. Anticoagulation should be initiated as quickly as possible, once it is deemed safe. A pooled analysis of three anticoagulation trials demonstrated that the risk of recurrent PE was 25 percent if the activated partial thromboplastin time (aPTT) was not therapeutic within the first 24 hours after initiation of heparin [23].
In contrast, empiric anticoagulation should be considered on a case by case basis if the clinical suspicion of PE is low to moderate or there is an increased risk of bleeding. Certain conditions that may be in the differential diagnosis of PE are contraindications to anticoagulation (eg, pericardial tamponade, aortic dissection). In this situation, diagnostic evaluation must be expedited so that therapies that do not require anticoagulation (eg, inferior vena caval filters) can be initiated if PE is confirmed.
GENERAL APPROACH — Once the patient has stabilized, the diagnostic evaluation should be performed as quickly as possible. Anticoagulation can be discontinued if PE is excluded.
If PE is confirmed, thrombolytic therapy should be considered. The indications for thrombolytic therapy are described elsewhere. (See "Fibrinolytic (thrombolytic) therapy in pulmonary embolism and deep vein thrombosis".) Those patients who are selected to undergo thrombolysis should have their anticoagulation temporarily discontinued during the thrombolytic infusion and resumed later. Embolectomy should be considered for patients whose presentation is severe enough to warrant thrombolysis, but in whom thrombolysis is either contraindicated or unsuccessful. (See 'Embolectomy' below.)
Long-term anticoagulation is indicated for patients with confirmed PE. (See "Anticoagulation in acute pulmonary embolism".) Those patients who have contraindications to anticoagulation, fail anticoagulation, or develop complications of anticoagulation (eg, severe bleeding) should have an inferior vena caval filter placed instead. (See 'Resuscitation' above and 'IVC filters' below.)
An algorithm for the management of PE is shown in the figure (algorithm 1).
ANTICOAGULANT THERAPY — Anticoagulant therapy reduces mortality and is considered primary therapy for PE [24]. The goal of anticoagulation is to decrease mortality by preventing recurrent PE.
Anticoagulant therapy should be initiated as soon as the decision has been made that anticoagulation is indicated. Its efficacy depends upon achieving a therapeutic level of anticoagulation within the first 24 hours of treatment [23,25-27]. (See 'Resuscitation' above, section on Anticoagulation).
The types of anticoagulants and therapeutic regimens used to treat acute PE are discussed separately. In addition, duration of therapy, complications, and risk factors for complications are presented elsewhere. (See "Anticoagulation in acute pulmonary embolism".)
THROMBOLYSIS — Thrombolytic therapy accelerates the lysis of acute PE (figure 1) and improves important physiologic parameters, such as RV function and pulmonary perfusion. However, no clinical trial has been large enough to conclusively demonstrate a mortality benefit. Thrombolytic therapy is associated with an increased risk of major hemorrhage, defined as intracranial hemorrhage, retroperitoneal hemorrhage, or bleeding leading directly to death, hospitalization, or transfusion [22,28-30].
Persistent hypotension due to PE (ie, massive PE) is the most widely accepted indication for thrombolytic therapy [31]. Some clinicians believe that thrombolysis should be considered on a case-by-case basis in certain other clinical circumstances, such as severe hypoxemia, large perfusion defects, right ventricular dysfunction, free-floating right atrial or ventricular embolus, and patent foramen ovale [12,31-33].
We emphasize that, in most cases, thrombolysis should be considered only after PE has been confirmed because the adverse effects of thrombolytic therapy can be severe.
The efficacy, indications, contraindications, and adverse effects of thrombolytic therapy for PE are discussed separately. The types of thrombolytic agents and thrombolytic regimens are also reviewed elsewhere. (See "Fibrinolytic (thrombolytic) therapy in pulmonary embolism and deep vein thrombosis".)
IVC FILTERS — Inferior vena caval (IVC) filters provide a screen in the inferior vena cava, allowing blood to pass through while preventing large emboli from traveling from the pelvis or lower extremities to the lung. We summarize the role of IVC filters in the management of acute PE here. A more detailed discussion about IVC filter types, indications, effectiveness, and complications is presented separately. (See "Inferior vena cava filters".)
Indications — Insertion of an inferior vena cava (IVC) filter is indicated for acute PE in the following settings [31]:
- Absolute contraindication to anticoagulation (eg, active bleeding)
- Recurrent PE despite adequate anticoagulant therapy
- Complication of anticoagulation (eg, severe bleeding)
- Hemodynamic or respiratory compromise that is severe enough that another PE may be lethal
Patients who have undergone embolectomy (surgical or catheter) frequently undergo IVC filter insertion. In addition, IVC filters are being used for PE prophylaxis in select groups of patients. While the evidence base for these indications is less robust, it appears reasonable to individualize such cases and consider this approach. (See "Inferior vena cava filters".)
Outcome — IVC filters decrease recurrent PE [34,35]. However, a reduction in mortality has not been conclusively demonstrated. One study suggested that IVC filters may decrease mortality in patients with persistent hypotension due to PE (ie, massive PE), but this is uncertain because the patients who received IVC filters were younger and the effect of age was not considered [32].
In one trial, 400 patients with proximal deep venous thrombosis (DVT) were randomly assigned to receive anticoagulation alone or anticoagulation plus an IVC filter [34]. The trial found:
- Fewer patients in the IVC filter group suffered PE within twelve days (1 versus 5 percent).
- Two years later, there was no difference in survival or symptomatic PE. However, recurrent DVT was more common among patients who received an IVC filter (21 versus 12 percent).
- Eight years later, there were fewer symptomatic PE in the IVC filter group (6 versus 15 percent). However, recurrent DVT was more common among patients who received an IVC filter (36 versus 27 percent) [35].
This trial suggests that the benefit of decreased recurrent PE must be weighed against the consequence of increased recurrent DVT when deciding whether an IVC filter should be placed in a patient with acute PE.
Complications — Complications of IVC filters are rare but include [34,36]:
- Complications related to the insertion process (eg, bleeding, venous thrombosis at the insertion site).
- Filter misplacement.
- Filter migration.
- Filter erosion and perforation of the IVC wall.
- IVC obstruction due to filter thrombosis.
(See "Inferior vena cava filters".)
Except when the indication is very clear, permanent IVC filter placement is discouraged in young patients with a long life expectancy because long-term outcomes and filter durability have not been well studied. To address concerns regarding potential adverse consequences in patients who have long-term IVC filters, retrievable (ie, temporary) IVC filters have been developed. However, investigation of their effectiveness and adverse effects is still in its early stages [37,38].
EMBOLECTOMY — Embolectomy (ie, removal of the emboli) can be performed using catheters or surgically. It should be considered when a patient's presentation is severe enough to warrant thrombolysis (eg, persistent hypotension due to PE), but this approach either fails or is contraindicated. (See 'General approach' above.)
Catheter embolectomy — Intrapulmonary arterial techniques (eg, rheolytic embolectomy, rotational embolectomy) have been utilized to reduce the embolic burden in patients with PE. Case series using these techniques are small, and none of the techniques has been compared with other forms of therapy in randomized, controlled studies. Larger studies are needed to determine which, if any, catheter technique is most effective compared to alternative treatment modalities.
Rheolytic embolectomy — Using a rheolytic embolectomy catheter (ie, the AngioJet embolectomy system), embolectomy is accomplished by injecting pressurized saline through the catheter's distal tip, which macerates the emboli [39]. The saline and fragments of clot are then sucked back into an exhaust lumen of the catheter for disposal. The major disadvantage of this system is that a large venous sheath or a venous cut-down is required to insert the large catheter, which increases the risk of bleeding at the insertion site.
In a case series of 12 patients with acute PE who underwent rheolytic embolectomy with or without catheter-directed thrombolysis, technical success was achieved in all 12 patients [40]. Ten patients (83 percent) survived and were discharged from the hospital, but two patients (17 percent) died due to cardiac arrest within 24 hours of the procedure.
Rotational embolectomy — Rotational catheter fragmentation of emboli has been performed using conventional cardiac catheters which do not require venotomy at the insertion site [41,42]. Newer catheters also exist that use a rotating device to fragment the thrombus, while continuously aspirating the fragments.
A case series of 20 patients treated with rotational embolectomy reported that approximately one-third of the procedures achieved recanalization, but mortality was high (20 percent) [42]. In a more recent case series, 18 patients with acute PE complicated by shock underwent catheter-directed rotational embolectomy, most with continuous aspiration of thrombotic fragments [43]. Clinical success was achieved in 16 cases (89 percent), defined as improvement in oxygenation and blood pressure without a major complication. One patient died from refractory shock.
Surgical embolectomy — Surgical embolectomy is typically limited to large medical centers because an experienced surgeon and cardiopulmonary bypass are required. Although systemic hypotension due to PE in a patient in whom thrombolysis is contraindicated is the usual indication for surgical embolectomy, echocardiographic evidence of an embolus trapped within a patent foramen ovale, the right atrium, or the right ventricle has also prompted surgery [44]. Thrombolysis should also be considered in this setting.
Surgical embolectomy has been compared to repeat thrombolysis in patients who failed initial thrombolysis. In a small observational cohort study, patients who underwent surgical embolectomy had fewer recurrent PE [45]. In addition, there were fewer deaths and fewer major bleeding complications among the surgical embolectomy group, although these differences did not achieve statistical significance. Surgical embolectomy has not been compared to catheter embolectomy or primary thrombolytic therapy.
Transesophageal echocardiography (TEE) should be performed before or during pulmonary embolectomy to look for extrapulmonary thrombi (ie, thrombi in the right atrium, right ventricle, or vena cava). In a series of 50 patients with PE, intraoperative TEE detected extrapulmonary thrombi in 13 patients (26 percent), which altered the surgical management of five patients (10 percent) [46].
Cardiac arrest predicts mortality during surgical embolectomy [47-51]. In one study of 36 patients with profound hypotension due to PE (but without cardiac arrest) who underwent surgical embolectomy, 35 patients survived [49]. In contrast, operative mortality among patients with PE who were resuscitated from a cardiac arrest, then underwent surgical embolectomy was approximately 75 percent [49,50]. Mortality after cardiac arrest due to PE is extremely high in the nonsurgical setting as well.
Whether surgical or catheter embolectomy is chosen depends on the availability of resources and expertise of the institution, since a direct comparison has never been performed and data regarding the effectiveness of each therapy are limited.
WITHHOLDING THERAPY — The diagnosis of PE almost invariably leads to treatment with anticoagulants or IVC filter placement. However, one retrospective analysis that used data from two prospective studies suggested that patients with PE who are hemodynamically stable, have adequate cardiopulmonary reserve, and have a contraindication to anticoagulation, can be safely observed without treatment if serial lower extremity venous ultrasounds are negative over 14 days [52]. Although intriguing, the data are clearly insufficient to recommend this approach.
INFORMATION FOR PATIENTS — Educational materials on this topic are available for patients. (See "Patient information: Pulmonary embolism".) We encourage you to print or e-mail this topic, or to refer patients to our public web site www.uptodate.com/patients, which includes this and other topics.
SUMMARY AND RECOMMENDATIONS
- When a patient presents with suspected pulmonary embolism (PE), initial care should focus on stabilizing the patient. Supplemental oxygen should be administered if hypoxemia exists. Patients with significant hypoxemia or hemodynamic compromise should be admitted to the intensive care unit. Severe hypoxemia or respiratory failure should prompt intubation and mechanical ventilation. (See 'Resuscitation' above.)
- If the patient presents with systemic hypotension, prompt hemodynamic support should be instituted. Intravenous fluid administration may be beneficial. However, clinicians should be wary of administering more than 500 to 1000 mL during the initial resuscitation period. (See 'Resuscitation' above.)
- For patients in whom there is a high clinical suspicion of PE and no excess risk of bleeding, we recommend that empiric anticoagulation be initiated immediately and continued during the diagnostic evaluation (algorithm 1) (Grade 1B). For patients in whom there is a low or moderate suspicion of PE or an increased risk of bleeding, decisions about empiric anticoagulation must be made on a case-by-case basis. (See 'Anticoagulation' above and "Anticoagulation in acute pulmonary embolism".)
- Once the decision has been made to initiate anticoagulant therapy, the anticoagulant must be chosen. The types of anticoagulants and therapeutic regimens used to treat acute PE are discussed separately. In addition, duration of therapy, complications, and risk factors for complications are presented elsewhere. (See 'Anticoagulant therapy' above and "Anticoagulation in acute pulmonary embolism".)
- For patients with confirmed PE who have contraindications to anticoagulation, complications of anticoagulation (eg, bleeding), recurrent PE despite therapeutic anticoagulation, or hemodynamic or respiratory compromise that is severe enough that another PE may be lethal, we suggest insertion of an inferior vena caval filter (Grade 2C). (See 'IVC filters' above.)
- In patients with PE in whom thrombolysis is indicated, but who fail thrombolysis or have contraindications to thrombolysis, we suggest catheter or surgical embolectomy if the necessary resources and expertise are available (Grade 2C). The decision of whether to pursue one of these approaches should be based on local expertise. (See 'Embolectomy' above.)
