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 3 to 8 percent, making it imperative that effective therapy be instituted as quickly as possible [7-9].
The clinical severity of acute 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:
Treatment of patients with acute PE is reviewed here. More detailed discussions regarding anticoagulation and thrombolysis in acute PE are presented separately. The epidemiology, prognosis, pathophysiology, risk factors, symptoms, signs, and diagnosis of acute PE are discussed separately. (See "Anticoagulation in acute pulmonary embolism" and "Fibrinolytic (thrombolytic) therapy in acute pulmonary embolism and lower extremity deep vein thrombosis" and "Overview of acute pulmonary embolism" and "Diagnosis of acute pulmonary embolism".)
RESUSCITATION — When a patient presents with suspected acute PE, the initial focus is on stabilizing the patient. This may require respiratory support, hemodynamic support, and/or empiric anticoagulation.
Respiratory support — Supplemental oxygen should be administered if hypoxemia exists. Severe hypoxemia or respiratory failure should prompt consideration of intubation and mechanical ventilation. Of note, patients with coexistent RV failure are prone to hypotension following intubation. The initiation of mechanical ventilation is discussed separately. (See "Overview of mechanical ventilation", section on 'Initiation'.)
Hemodynamic support — Hemodynamic support should be instituted when a patient presents with acute PE and hypotension. Hypotension may be roughly defined as a systolic blood pressure <90 mmHg or a drop in systolic blood pressure of ≥40 mmHg from baseline, but the precise thresholds that warrant hemodynamic support depend to some degree upon the patient’s baseline blood pressure and whether there is clinical evidence of hypoperfusion (eg, change in mental status, diminished urine output).
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 <2.5 L/min/m2 [10]. Administration of 500 mL of dextran significantly increased the cardiac index 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 [11-15]. Clinicians should be wary of administering more than 500 to 1000 mL of normal saline during the initial resuscitation period [12]. If the patient's blood pressure and hemodynamic status do not improve with intravenous fluids, then intravenous vasopressor therapy should promptly follow.
There are no randomized trials that definitively determine the optimal vasopressor for patients with shock due to acute PE:
Physiologic properties and practical issues regarding the use of vasopressors are discussed separately. (See "Use of vasopressors and inotropes".)
Empiric anticoagulation — PE-directed therapy should be considered during the resuscitative period (figure 1). Empiric anticoagulation is indicated when there is no excess risk for bleeding and there is a high clinical suspicion of acute PE, a moderate clinical suspicion for acute PE and the diagnostic evaluation is expected to take longer than four hours, or a low clinical suspicion for acute PE and the diagnostic evaluation is expected to take longer than 24 hours [9]. Stratification of clinical suspicion and the initiation of empiric anticoagulant therapy for suspected acute PE are discussed separately. (See "Anticoagulation in acute pulmonary embolism", section on 'Initiation of anticoagulant therapy'.)
Once it has been determined that empiric anticoagulant therapy is indicated, it should be initiated as soon as possible because its efficacy may be related to achieving therapeutic levels of anticoagulation within the initial 24 hours. 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 [21].
In contrast to the approach for patients with no excess risk for bleeding, empiric anticoagulant therapy should be considered on a case-by-case basis if there is a moderate or high risk of bleeding, or if there are conditions in the differential diagnosis that are contraindications to anticoagulation (eg, pericardial tamponade, aortic dissection). If anticoagulant therapy is judged to be contraindicated, the diagnostic evaluation must be expedited so that therapies that do not require anticoagulation (eg, inferior vena caval filter, embolectomy) can be initiated if acute PE is confirmed. Stratification of the risk of bleeding as low, moderate, or high is described separately. (See "Anticoagulation in acute pulmonary embolism", section on 'Initiation of anticoagulant therapy'.).
POST-RESUSCITATION — The diagnostic evaluation should be performed as quickly as possible once the patient has been stabilized. (See "Diagnosis of acute pulmonary embolism".)
For patients in whom the diagnostic evaluation EXCLUDES an acute PE, anticoagulant therapy should be discontinued if it was initiated empirically during the resuscitative period. Alternative causes of the patient’s symptoms and signs should be sought.
For patients in whom the diagnostic evaluation CONFIRMS an acute PE:
This approach is depicted in an algorithm for the management of suspected acute PE (figure 1).
Anticoagulant therapy — Anticoagulant therapy is considered primary therapy for acute PE. It is discussed in detail separately, including indications for empiric therapy, assessment of the risk for bleeding, anticoagulant agents, dosing, monitoring, outcomes, and duration of therapy. (See "Anticoagulation in acute pulmonary embolism".)
Thrombolytic therapy — Thrombolytic therapy is generally considered for patients with severe clinical manifestations. Thrombolytic therapy for acute PE is reviewed in detail separately, including the indications, contraindications, agents, administration, and outcomes. (See "Fibrinolytic (thrombolytic) therapy in acute pulmonary embolism and lower extremity deep vein thrombosis".)
IVC filters — Inferior vena caval (IVC) filters provide a screen in the inferior vena cava, allowing blood to pass through while large emboli from the pelvis or lower extremities are blocked or fragmented before reaching the lung. Placement of an IVC filter is generally considered in patients who have contraindications to anticoagulation, failed anticoagulation, or developed a complication due to anticoagulation. In addition, IVC filter placement is often considered when the hemodynamic or respiratory compromise is severe enough that another PE may be lethal. IVC filter indications, types, outcomes, and complications are reviewed separately. (See "Inferior vena cava filters".)
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 acute PE), but thrombolytic therapy either fails or is contraindicated. Whether surgical or catheter embolectomy is chosen depends upon 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.
Catheter embolectomy — Rheolytic embolectomy, rotational embolectomy, suction embolectomy, thrombus fragmentation, and ultrasound plus low-dose thrombolytic therapy are techniques that have been utilized to reduce the embolic burden in patients with acute PE. Case series using these techniques are small and none of the techniques has been compared with other forms of therapy in randomized trials. Larger studies are needed to determine which, if any, catheter technique is most effective compared to alternative treatment modalities.
Surgical embolectomy — Surgical embolectomy is typically limited to large medical centers because an experienced surgeon and cardiopulmonary bypass are required. Although the usual indication for surgical embolectomy is systemic hypotension due to acute PE in a patient in whom thrombolysis is contraindicated, surgery has also been prompted by echocardiographic evidence of an embolus trapped within a patent foramen ovale, the right atrium, or the right ventricle [29].
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 [30]. 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) [31].
Cardiac arrest predicts mortality during surgical embolectomy [32-36]. In one study of 36 patients with profound hypotension due to acute PE (but without cardiac arrest) who underwent surgical embolectomy, 35 patients survived (97 percent) [34]. In contrast, operative mortality among patients with acute PE who were resuscitated from a cardiac arrest, then underwent surgical embolectomy was approximately 75 percent [34,35]. Mortality after cardiac arrest due to acute PE is high in the nonsurgical setting as well.
INPATIENT OR OUTPATIENT THERAPY — Not all patients who have symptomatic acute PE need to be admitted to the hospital for initial therapy. Patients who do not require supplemental oxygen and have a normal pulse, normal blood pressure, and no recent history of bleeding, may reasonably be considered for outpatient management if they do not have serious comorbid conditions (eg, ischemic heart disease, liver or renal failure, thrombocytopenia) [9,37]. Additional considerations include the amount of support from family and friends, access to a telephone, and the ability to return to the hospital quickly if there is clinical deterioration [9].
This is supported by several observational studies [38-40] and a randomized trial that showed no significant differences in outcomes when patients treated as outpatients were compared with patients treated as inpatients [41]. In the trial, 344 patients with symptomatic acute PE and a low risk of death were randomly assigned to receive either inpatient or outpatient therapy with low molecular weight heparin followed by oral anticoagulation [41]. Within 90 days, recurrent venous thromboembolism occurred in one outpatient (0.6 percent) and no inpatients, death occurred in one outpatient and one inpatient, and major bleeding occurred in three outpatients (1.8 percent) and no inpatients. The mean length of stay was 0.5 days for outpatients and 3.9 days for inpatients. The trial defined a low risk of death as falling within pulmonary embolism severity index (PESI) class I or II. The PESI is described separately. (See "Overview of acute pulmonary embolism", section on 'Prognosis'.)
In stable patients being considered for outpatient therapy or early discharge, it is logical that an important risk factor for poor outcome would be residual clot burden in the legs. In fact, in patients with a first episode of acute symptomatic PE, the presence of concomitant deep vein thrombosis (DVT) has been shown to be an independent predictor of death in the ensuing three months after diagnosis [42]. Thus, when outpatient therapy of acute PE is considered, the clinician may wish to evaluate the legs prior to discharge (ie, assessment of the thrombotic burden may assist with risk stratification of these patients).
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