Acute pulmonary embolism in adults: Treatment overview and prognosis

INTRODUCTION — 

Acute pulmonary embolism (PE) is a common and sometimes fatal disease with variable clinical presentation. It is critical that therapy be administered in a timely fashion to avoid fatalities [1-5].

The treatment, prognosis, and follow-up of patients with acute PE are reviewed here. The epidemiology, pathophysiology, clinical presentation, and diagnosis of PE, as well as detailed discussions of anticoagulation and thrombolysis in patients with PE are presented separately.

●(See "Pulmonary embolism: Epidemiology and pathogenesis in adults".)

●(See "Clinical presentation and diagnostic evaluation of the nonpregnant adult with suspected acute pulmonary embolism".)

●(See "Acute pulmonary embolism in adults: Thrombolytic therapy in intermediate- and high-risk patients".)

●(See "Venous thromboembolism: Initiation of anticoagulation".)

The approach to treatment in this topic is, in general, consistent with strategies outlined by several international societies [6-10].

INITIAL RESUSCITATION, RISK ASSESSMENT, EMPIRIC ANTICOAGULATION — 

For patients with PE, we provide supportive therapy (table 1) and rapidly assess the risk of death from PE.

Supportive therapies

Respiratory support — Our approach is as follows:

●Supplemental oxygen – We administer supplemental oxygen to target a peripheral oxygen saturation ≥90 percent using low- or high-flow systems depending on the patient's needs. Management of hypoxemic respiratory failure is discussed separately. (See "Evaluation and management of the nonventilated, hospitalized adult patient with acute hypoxemia", section on 'Oxygen and respiratory support'.)

●Mechanical ventilation – Mechanical ventilation is a last resort measure for patients with severe hypoxemia or pending cardiac or respiratory arrest. Importantly, induction medications in patients with coexistent right ventricle (RV) failure may induce an RV crisis resulting in severe hypotension, shock, and cardiac arrest. Thus, in this population, it is reasonable to consult an expert in cardiovascular anesthesia. For this reason, we also inform the extracorporeal membrane oxygenation (ECMO) team in advance should their assistance be needed. The principles of intubation, mechanical ventilation, and ECMO are discussed separately. (See "Induction agents for rapid sequence intubation in adults for emergency medicine and critical care" and "Direct laryngoscopy and endotracheal intubation in adults" and "Overview of initiating invasive mechanical ventilation in adults in the intensive care unit", section on 'Indications' and "Extracorporeal life support in adults in the intensive care unit: Overview".)

We avoid high plateau pressures since they reduce lung compliance, thereby decreasing venous return and exacerbating RV failure. We also avoid hypercapnia, which induces vasoconstriction, thereby increasing RV afterload and worsening RV failure.

Limited data suggest that inhaled nitric oxide may be trialed in patients with refractory hypoxemia due to PE [11,12]. (See "Inhaled nitric oxide in adults: Biology and indications for use" and "Inhaled nitric oxide in adults: Biology and indications for use", section on 'Acute hypoxemic respiratory failure'.)

Hemodynamic support — Administering hemodynamic support depends upon the patient's volume status, baseline blood pressure (BP), evidence of tissue hypoperfusion (eg, change in mental status, diminished urine output), and previous fluid administered during diagnostic evaluation.

●Intravenous fluid – There is no ideal resuscitation volume or fluid choice. In general, we prefer small volumes of intravenous fluid, usually two to three boluses of 250 to 500 mL of normal saline or buffered salt solution. However, in patients with RV dysfunction, limited data in preclinical studies and our experience suggest that aggressive fluid resuscitation is not beneficial and may be harmful. For example, small volumes increase the cardiac index in PE while excessive amounts result in RV overload, RV ischemia, and worsening RV failure [8,13-16].

●Vasopressors – We have a low threshold to initiate vasopressor therapy when adequate perfusion is not restored with low-volume intravenous fluid. The optimal vasopressor for patients with shock due to acute PE is unknown, but norepinephrine is generally preferred (table 2) [14,17-19].

•Norepinephrine – Norepinephrine is the most frequently utilized agent in this population because it is effective and less likely to cause tachycardia [14]. (See "Use of vasopressors and inotropes".)

•Dobutamine – Dobutamine is sometimes used to increase myocardial contractility in patients with circulatory shock from PE. However, it also results in systemic vasodilation, which worsens hypotension, particularly at low doses [18,19]. To mitigate this effect, we typically combine norepinephrine and dobutamine, at least initially; as the dose of dobutamine is increased, the effects of dobutamine-induced myocardial contractility exceed those of vasodilation, potentially allowing norepinephrine to be weaned off.

•Others – Other alternatives include dopamine or epinephrine, but tachycardia, which can exacerbate hypotension, can occur with these agents [17].

Isoproterenol, amrinone, and milrinone have been investigated in animal models, but have not proven useful for hypotension due to acute PE [20,21].

Physiologic properties and use of vasopressors are discussed separately. (See "Use of vasopressors and inotropes".)

●ECMO – Venoarterial (V-A) ECMO may be used in patients with high-risk PE who have RV shock resistant to intravenous fluid and vasopressors. In such cases, V-A ECMO can be used as a bridge to definitive treatment (eg, thrombolysis or surgical embolectomy if thrombolytic therapy is contraindicated).

Further details are provided separately. (See "Extracorporeal life support in adults in the intensive care unit: Overview" and "Extracorporeal life support in adults: Management of venoarterial extracorporeal membrane oxygenation (V-A ECMO)".)

Assess mortality risk (low, intermediate, high) — We assess the risk of death from PE using the following (table 3):

●Clinical evaluation to calculate the PE severity index (PESI) or simplified PESI (sPESI) (table 4). (See 'Prognostic models' below.)

●Evaluation of RV function using imaging (computed tomography [CT] and/or echocardiography) and biochemical markers (troponin and brain natriuretic peptide [BNP], N-terminal pro-BNP). Most often, the diagnostic CT pulmonary angiogram identifies RV dilation, which may suggest dysfunction, but we prefer bedside or formal echocardiography for accurate functional assessment.

●Evaluation of additional high risk factors listed on the table (table 5).

We then assign risk as low, intermediate, or high. Most patients have low-risk PE and less commonly intermediate-risk PE [22,23] while <10 percent present with hemodynamic instability or shock (ie, high-risk PE). Risk stratification guides therapy and identifies those that may need transfer to a facility (eg, intermediate- or high-risk PE) for the potential provision of some therapies that are not universal (eg, thrombolytic therapy, catheter-directed therapy, embolectomy). Such risk stratification often requires expert consultation. (See 'Pulmonary embolism response teams' below.)

●Low-risk PE – Low-risk PE is comprised of patients who are hemodynamically stable and have normal RV size and function with normal RV biomarkers, and a PESI score I/II (<86) or sPESI of zero (table 4).

●Intermediate-risk PE (also known as "submassive" PE) – Intermediate-risk PE is associated with evidence of RV dysfunction but without systemic hypotension (usually reflected by a PESI score III to V [≥86] or an sPESI score ≥1 (table 4)). We agree with the European Society of Cardiology (ESC) guidelines [8] to further subcategorize this population into the following:

•Intermediate-low risk – Abnormal RV function on imaging or elevated biomarker(s)

•Intermediate-high risk – Abnormal RV function and elevated biomarker(s)

These subcategories help identify those at greatest risk of death within the intermediate category who may benefit from thrombolysis. (See 'Pulmonary embolism response teams' below and 'Thrombolytic therapy' below.)

●High-risk PE (also known as "massive" or "unstable" PE) – Patients with high-risk PE are a heterogeneous group ranging from patients who present with hypotension to patients with cardiac arrest or obstructive shock. PESI or measurement of RV biomarkers, although often measured, are often not necessary since these features typically represent significant RV dysfunction.

Clinically significant hypotension is defined as a systolic BP <90 mmHg or hypotension that requires vasopressors or inotropic support despite adequate filling status in combination with end-organ hypoperfusion; persistent hypotension or a drop in systolic BP of ≥40 mmHg from baseline for a period >15 minutes; hypotension not explained by other causes, such as hypovolemia, sepsis, arrhythmia, or left ventricular dysfunction from acute myocardial ischemia or infarction.

Although hemodynamically unstable PE is often caused by large (ie, massive) PE, it can sometimes be due to small PE in patients with underlying cardiopulmonary disease. Thus, the term "massive" PE does not necessarily describe the size of the PE as much as its hemodynamic effect.

Importantly, death from high-risk PE often occurs within the first two hours, and the risk remains elevated for up to 72 hours after presentation [24,25].

In addition, patients may become hemodynamically stable following resuscitation or become unstable during the evaluation and early treatment period, both of which necessitate rapid redirection of therapeutic strategies.

However, this risk assessment has limitations including the following:

●Evidence of RV dysfunction may be present despite a calculated sPESI of 0, and such patients may potentially benefit from thrombolysis if they meet other high-risk criteria (table 5).

●Certain older adult patients, or those with underlying cardiac disease or on beta blockers, may have an inappropriately low heart rate response to the stress of PE.

●Some patients with acute PE may have an oxygen saturation of >90 percent at rest but desaturate significantly with exertion (eg, sitting up in bed) or have postural hypotension. These features are not accounted for in the sPESI.

Such limitations underscore the importance of expert consultation. (See 'Pulmonary embolism response teams' below.)

Empiric anticoagulation or thrombolysis — In the absence of a diagnosis, the administration of empiric anticoagulation depends upon the risk of bleeding, clinical suspicion for PE (calculator 1), the patient's hemodynamic status, and the expected timing of diagnostic tests [5,26]. One strategy is described below:

●Patients who are not at high risk for bleeding – The following is a reasonable strategy for patients who are not at high risk of bleeding:

•High suspicion for PE – For patients with a high clinical suspicion for PE (eg, Wells score >6), anticoagulant therapy should be started immediately. In such cases, the benefits of preventing death from further PE significantly outweigh the risk of bleeding.

For patients in this category who are hemodynamically unstable (ie, high-risk of death from PE), the administration of a thrombolytic agent as a life-saving measure should be individualized. All efforts should be made to obtain imaging that supports the diagnosis (eg, by CT pulmonary angiography [some emergency departments have local CT scanner], portable perfusion scanning, bedside echocardiography, bedside lower extremity compression ultrasonography). (See "Acute pulmonary embolism in adults: Thrombolytic therapy in intermediate- and high-risk patients", section on 'Should the diagnosis be confirmed?' and "Clinical presentation and diagnostic evaluation of the nonpregnant adult with suspected acute pulmonary embolism", section on 'High probability of pulmonary embolism'.)

•Moderate suspicion for PE – For patients with a moderate clinical suspicion for PE (eg, Wells score 2 to 6), anticoagulant therapy can be started when the diagnostic evaluation is expected to take >4 hours.

•Low suspicion for PE – For patients with a low clinical suspicion for PE (eg, Wells score <2), anticoagulant therapy can be started when the diagnostic evaluation is expected to take >24 hours.

●Patients with contraindications or at high risk for bleeding – For patients with absolute contraindications to anticoagulant therapy (eg, recent surgery, hemorrhagic stroke, active bleeding aortic dissection, intracranial or spinal cord tumors), empiric anticoagulation should not be administered.

For patients without contraindications who have a high risk of bleeding (eg, >13 percent), empiric anticoagulant therapy is administered on a case-by-case basis using our clinical judgement. As an example, we might empirically administer anticoagulant therapy to a patient with a high risk of bleeding if they have a high clinical suspicion for PE with severe respiratory compromise and an expected delay for the insertion of an inferior vena cava (IVC) filter.

In all cases, the diagnostic evaluation should be expedited, if feasible, so that alternate therapies (eg, IVC filter, embolectomy) can be promptly initiated if PE is confirmed.

Typically, menstruation, epistaxis, and the presence of minor hemoptysis are not contraindications to anticoagulation but should be monitored during anticoagulant therapy. It is common that patients with PE may have hemoptysis largely due to pulmonary infarction, and anticoagulation should not be stopped or considered contraindicated for that reason.

The optimal agent for empiric anticoagulation depends upon the presence or absence of hemodynamic instability, the anticipated need for procedures or thrombolysis, and the presence of risk factors and comorbidities (table 6). As an example, low molecular weight (LMW) heparin may be chosen for patients with hemodynamically stable PE who do not have kidney function impairment and in whom rapid onset of anticoagulation needs to be guaranteed (ie, therapeutic levels are achieved with four hours). While unfractionated heparin is preferred by many experts in patients who are hemodynamically unstable in anticipation of a potential need for thrombolysis or embolectomy, some trials with catheter-based treatments allowed patients on background LMW heparin [27,28]. Direct thrombin and factor Xa inhibitors should not be used in hemodynamically unstable patients.

In hemodynamically unstable patients with suspected PE (ie, at high risk of death from PE), a thrombolytic agent may need to be administered empirically, the details of which are discussed separately. (See "Acute pulmonary embolism in adults: Thrombolytic therapy in intermediate- and high-risk patients", section on 'Should the diagnosis be confirmed?'.)

Pulmonary embolism response teams — For patients with intermediate- or high-risk PE (table 3), we adopt a multidisciplinary approach to facilitate management or transfer to a facility for specific therapies that are not universally available. Multidisciplinary teams have been termed "pulmonary embolism response teams" (PERTs) and include pulmonologists, intensivists, cardiologists, thoracic surgeons, interventional radiologists, vascular surgeons, emergency department clinicians, hematologists, and/or pharmacists [23,29-31].

The 2019 ESC guidelines include a conditional recommendation for PERTs based upon limited data [8]. For example, a meta-analysis of 22 mostly retrospective studies reported that PERT led to greater use of advanced therapies and shorter in-hospital stay, but had no survival benefit [32].

DEFINITIVE THERAPY — 

For patients with confirmed PE, we use an approach that is stratified according to the risk of death from PE (algorithm 1 and algorithm 2). At any time, the strategy may need to be redirected as complications of PE or therapy arise (eg, altered risk of bleeding, worsening hemodynamic status). (See 'Low-risk PE' below and 'High-risk PE (unstable)' below and 'Intermediate-risk PE' below.)

Low-risk PE — Low-risk PE is not associated with right ventricular (RV) dysfunction or hypotension.

Anticoagulation — For patients in whom the risk of bleeding is not high, we recommend anticoagulant therapy. Anticoagulation reduces the risk of further embolization and PE-related death. While data are flawed, if left untreated, PE is associated with an overall mortality of up to 30 percent compared with 2 to 11 percent in those treated with anticoagulation [1,4,24,25,33,34]. Details regarding agent selection (table 6) and duration are provided separately. (See "Venous thromboembolism: Initiation of anticoagulation" and "Venous thromboembolism: Anticoagulation after initial management".)

Agent selection and duration — Initial agent selection and duration (typically three months) including indications for indefinite anticoagulation are provided in separate topic reviews:

●Initial anticoagulation – (See "Venous thromboembolism: Initiation of anticoagulation" and 'Outpatient anticoagulation' below.)

●Long-term anticoagulation (after discharge) – (See "Venous thromboembolism: Anticoagulation after initial management".)

●Indefinite anticoagulation – (See "Selecting adult patients with lower extremity deep venous thrombosis and pulmonary embolism for indefinite anticoagulation".)

Patients with subsegmental PE — The increasing use of CT has led to the increased diagnosis of incidental (asymptomatic) and subsegmental PE (SSPE) (figure 1).

●Incidence – The true proportion of patients with SSPE is unknown. A meta-analysis of 14 studies reported a pooled prevalence of 4.6 percent [35].

●Treatment – Whether or not patients with SSPE should receive anticoagulant therapy is controversial [9,36]. Practice varies widely. While some clinicians administer anticoagulant therapy to all patients with SSPE, others avoid anticoagulation in a minority of individuals (especially if a more convincing etiology is discovered on CT for the patient's symptoms) [37].

Our approach to anticoagulant therapy in patients with SSPE is the following:

•Most patients with SSPE should undergo therapeutic anticoagulation [5,9]. This practice is based upon the biologic rationale that untreated PE may result in a subsequent fatal event and limited data that suggest similar outcomes when SSPE is compared with proximal PE (see outcomes bullet below). Anticoagulant therapy is particularly important when PE is unprovoked, persistent risk factors (such as active cancer and acute hospitalization with prolonged immobility) are present, defects are multiple, symptoms are present, and/or patients have limited cardiorespiratory reserve. (See "Venous thromboembolism: Anticoagulation after initial management" and "Venous thromboembolism: Initiation of anticoagulation".)

The optimal duration of anticoagulation is unknown, but we treat SSPE similarly to segmental or lobar PE (ie, minimum of three months). Anticoagulant therapy beyond that period is discussed separately. (See "Venous thromboembolism: Initiation of anticoagulation" and "Selecting adult patients with lower extremity deep venous thrombosis and pulmonary embolism for indefinite anticoagulation", section on 'Incidental subsegmental PE without identifiable risk factors'.)

•Experts also agree that a small subset of patients may reasonably opt for no anticoagulation, provided the risk of recurrence is considered low and patients are monitored appropriately. This includes the following:

-Patients with a single small defect (ie, seen on one image) in whom there is no evidence of proximal lower extremity deep vein thrombosis (DVT) or evidence of thrombus elsewhere (eg, upper extremity clot) [9].

-Patients in whom a false positive test is suspected.

-Patients with preserved baseline cardiorespiratory function.

-Patients with a low pretest probability and normal D-dimer.

When clinical surveillance is chosen, we suggest serial testing with bilateral proximal compression ultrasonography (CUS) of the lower extremities in two weeks to look for evidence of proximal thrombus. We also have a low threshold to repeat diagnostic imaging for PE should symptoms persist or recur. This strategy is based upon the rationale that serial CUS has been reported to be safe in patients with nondiagnostic testing for PE (eg, indeterminate or low probability ventilation-perfusion scanning); details regarding this strategy are described separately. (See "Clinical presentation and diagnostic evaluation of the nonpregnant adult with suspected acute pulmonary embolism", section on 'Lower-extremity ultrasound'.)

Despite support for this strategy, many clinicians are not adopting the practice [38].

●Outcomes – Although the clinical relevance of SSPE is unknown, limited data suggest that outcomes are similar to those with proximal emboli.

•A retrospective review of 222 patients with PE, 36 percent of whom had SSPE, reported that adverse events were similar between patients with SSPE and patients with more proximal emboli [39].

•Combined data from two prospective studies of 748 patients with PE reported that those with SSPE had similar rates of mortality compared with patients with proximal PE (10 versus 7 percent) and recurrence (4 versus 3 percent) at three months [40]. Death in patients with SSPE was largely determined by comorbidities including malignancy, increasing age, male sex, chronic obstructive pulmonary disease, and heart failure.

•The incidence of venous thromboembolism (VTE) recurrence is unclear. While older retrospective studies suggested low recurrence rates [40-42], newer data suggest similar or higher than expected recurrence rates. In a prospective study of 292 patients with isolated SSPE and no lower extremity DVT who were managed without anticoagulation, the recurrence rate was 3.1 percent at 90 days (ie, higher than the expected rate in the general population of approximately 1 percent or less) [43]. Rates were higher in those with multiple SSPEs compared with a single isolated PE (5.7 versus 2.1 percent) and in older patients compared with those younger than 65 years (5.5 versus 1.8 percent). No fatalities were reported. However, this study was stopped early for benefit, which may have influenced the results. Other studies report similar recurrence rates at three months when SSPE and proximal PE are compared (4 versus 3 percent) [40].

Further details regarding the prognosis of PE are provided below. (See 'Prognosis' below.)

Outpatient anticoagulation — In select low-risk patients with PE (table 3), outpatient therapy can be administered by giving the first dose of an anticoagulant in the hospital or urgent care center, with the remaining doses given at home. Guideline groups, randomized trials, and meta-analyses suggest that outpatient anticoagulation is safe and effective in carefully selected patients with PE with all of the following features (table 7) [5,44-55]:

●Low risk of death, defined as Pulmonary Embolism Severity Index (PESI) class I or II (table 4) or simplified PESI (sPESI) score of 0 (see 'Prognostic models' below)

●No requirement for supplemental oxygen

●No requirement for narcotics for pain control

●No respiratory distress (not defined by guidelines)

●Normal pulse and blood pressure (not defined by guidelines)

●No recent history of bleeding or risk factors for bleeding

●No serious comorbid conditions (eg, ischemic heart disease, chronic lung disease, liver or kidney failure, thrombocytopenia, or cancer)

●Normal mental status with good understanding of risk and benefits, not needle averse (if low molecular weight heparin is chosen), and good home support without barriers to discharge (eg, do not live alone, have access to a telephone and clinician, can return to the hospital quickly if there is clinical deterioration)

●Absence of concomitant DVT (a high clot burden in the proximal veins of the lower extremities may increase the risk of recurrence or death)

●Ready access to direct oral anticoagulants

Since many of these criteria are subjective, the decision to treat as an outpatient involves clinical judgment and patient preferences.

Support for outpatient therapy or early discharge following a brief inpatient stay is derived from observational studies and a small number of randomized studies that include heterogeneous populations and regimens [9,48,50,52]. As examples:

●Several meta-analyses report similar rates of recurrence and mortality when outpatient therapy is compared with inpatient therapy [50,52,56,57]. Most of these trials used warfarin as the oral anticoagulant of choice. However, a 2019 analysis of two randomized trials reported similar 30- or 90-day mortality, major bleeding, and recurrence when low-risk patients with acute PE were treated as an inpatient or outpatient [56]. One of the included studies used rivaroxaban as the discharge anticoagulant of choice [58].

●In a subsequent prospective analysis of 525 patients with PE who were discharged early and treated with rivaroxaban, only three patients (0.6 percent) developed symptomatic nonfatal VTE recurrence at three months follow-up and bleeding rates were low (1.2 percent) [59].

Agent selection for outpatient anticoagulant therapy in patients with PE is similar to that for DVT. (See "Overview of the treatment of lower extremity deep vein thrombosis (DVT)", section on 'Outpatient therapy'.)

Although the practice of outpatient anticoagulation is increasing, rates vary among studies (2 to 38 percent) and some data suggest that it may be underutilized [60-63]. A cross sectional study of over 1.6 million emergency department (ED) visits for PE in the United States reported that discharge rates were unchanged between 2012 and 2020 (38 versus 33 percent) [62]. Among the patients who were considered low-risk (according to the PESI score (table 4)), approximately one-third were discharged from the ED. Patients at teaching hospitals and those with private insurance were more likely to receive a factor Xa inhibitor at discharge (eg, apixaban, rivaroxaban). However, other factors may have prevented patients from being discharged from the ED, such as drug accessibility and cost, concurrent DVT, poor social support, or RV burden. Although comorbidities may have contributed to low rates of discharge, rates were similar between those treated as outpatients and those treated as inpatients. Whether clinician education using prompts derived from electronic health records might improve rates is unclear but promising [61].

Contraindications to anticoagulation: Inferior vena cava filter — For patients with contraindications to anticoagulation or an unacceptably high bleeding risk, we suggest prompt placement of an inferior vena cava (IVC) filter, even in the absence of proven lower extremity thrombus (thrombus may remain undetected in the pelvis or calf veins or clot can quickly reform in the leg veins after embolization). This approach is based upon limited data in patients with DVT that IVC filters can prevent PE recurrence. Data in patients with PE are even more limited. A conventional course of anticoagulation should be administered once the contraindication resolves and the filter removed at a later date. (See "Placement of vena cava filters and their complications".)

Similarly, an IVC filter is appropriate in patients who develop contraindications while on anticoagulation; however, filter placement in this population depends upon the planned duration of anticoagulation and risk of recurrence when anticoagulation is discontinued.

Occasionally, we administer anticoagulant therapy on an individual basis if, for example, there is severe respiratory compromise and an expected delay for the insertion of a vena cava filter.

While clinical data are lacking, other anecdotal indications for an IVC filter exist. A multidisciplinary approach involving the PE response team may facilitate the decisions to place an IVC filter under the following circumstances:

●Recurrence despite therapeutic anticoagulation.

●Patients who have large clot burden in the pulmonary arteries with proximal DVT.

●Patients in whom another embolic event would be poorly tolerated (eg, poor cardiopulmonary reserve, severe hemodynamic or respiratory compromise).

●Patients with a high risk of recurrence in whom it is anticipated that anticoagulation may need to be discontinued because of bleeding (eg, patients at moderate risk of bleeding who cannot receive fresh frozen plasma or red cells due to due to religious preference, patients with extensive metastatic malignancy who have a high risk for both recurrence and bleeding).

Retrievable filters should be used such that once the contraindication has resolved, the filter can be removed, and patients should be anticoagulated. A femoral intravenous access line with a "built-in" IVC filter that can be opened when the line is placed and removed when the line is removed has been described [64].

However, the decision to place an IVC filter, most of which are infrarenal, is modified in the following settings:

●If the patient has confirmed extensive upper extremity thrombosis in the absence of lower extremity thrombosis, an IVC filter will not be effective; and a superior vena cava filter may be useful.

●If the thrombus is in the renal vein (identified by the initial CT angiogram or during placement of the IVC filter), a suprarenal filter is appropriate.

Data describing outcomes in patients with PE who have IVC filters placed are limited:

●A randomized trial (PREPIC2) reported outcomes in 399 patients with severe PE (eg, older patients >75 years, active cancer, signs of RV dysfunction, chronic respiratory insufficiency) who received either standard anticoagulation alone or anticoagulation plus an IVC filter that was retrieved at three months [65]. The addition of an IVC filter to anticoagulation did not alter the rate of PE recurrence (1.5 versus 3 percent), DVT recurrence (0.5 percent), or mortality (7.5 versus 6 percent). The lack of benefit associated with IVC filter placement was persistent at six months. The rate of filter complications was low (<2 percent).

●Data derived from the Nationwide Inpatient Sample reported that the insertion of an IVC filter in hemodynamically stable patients with PE did not improve in-hospital mortality but was associated with a lower in-hospital case fatality rate among unstable patients who received thrombolytic therapy (8 versus 18 percent) as well as unstable patients who did not receive thrombolytic therapy (33 versus 51 percent) [66,67].

●Another database analysis of over 13,000 patients with PE who were treated with either thrombolytic or anticoagulant therapy reported a reduction in in-hospital mortality in those who were adjunctively treated with an IVC filter compared with those who did not receive a filter (3 versus 5 percent) [68].

●Data in patients with DVT suggest that IVC filters can prevent recurrent PE. These data are discussed in a separate topic review. (See "Overview of the treatment of lower extremity deep vein thrombosis (DVT)", section on 'Risks'.)

The placement and complications of IVC filters are presented separately. (See "Placement of vena cava filters and their complications" and "Overview of the treatment of lower extremity deep vein thrombosis (DVT)", section on 'IVC filters'.)

Intermediate-risk PE — Our approach is the following:

●Anticoagulation – Most patients with intermediate-risk PE are anticoagulated similar to low-risk patients. (See 'Anticoagulation' above.)

●Close monitoring – These patients should be monitored closely for deterioration, especially those with intermediate-high risk PE. This involves paying close attention to oxygenation, blood pressure, and heart rate changes. For example, the development of tachycardia >120 beats per minute and reduction in oxygenation may be predecessors of acute hypotension, such that the threshold should be low to switch to a different intervention like thrombolysis.

●Expert evaluation for potential thrombolytic therapy or thrombectomy – Expert consultation should be obtained to identify patients who may benefit from thrombolytic therapy or thrombectomy, which is controversial in this population. Patients on the high end of the intermediate-risk spectrum may benefit from thrombolysis/thrombectomy ("intermediate-high;" abnormal RV function and elevated brain natriuretic peptide [BNP] or troponin) while patients on the lower end may be less likely to benefit (intermediate-low; abnormal RV function or elevated BNP or troponin) (table 3). Other clinical factors that determine poor prognosis should also be taken into consideration (table 5 and table 8). Further details regarding patient selection and administration of thrombolytic therapy are discussed separately. (See "Acute pulmonary embolism in adults: Thrombolytic therapy in intermediate- and high-risk patients", section on 'Catheter-directed thrombolysis'.)

High-risk PE (unstable) — In patients with PE who are hemodynamically unstable or who become unstable due to recurrence despite anticoagulation, we use the following approach (algorithm 1 and algorithm 2):

●Systemic thrombolytic reperfusion therapy is indicated in most patients, provided there is no contraindication (table 9). (See "Acute pulmonary embolism in adults: Thrombolytic therapy in intermediate- and high-risk patients", section on 'Hemodynamically unstable (high-risk pulmonary embolism)'.)

●When thrombolysis is contraindicated or bleeding risk is unacceptably high, catheter-based procedures or surgical embolectomy is appropriate [69-72]. Additional indications for surgical embolectomy may include unsuccessful thrombolysis or thrombus trapped within a patent foramen ovale, right atrium, or RV [73]. (See 'Embolectomy' below.)

Reperfusion therapy

Thrombolytic therapy — The indications, contraindications, agents, administration, and outcomes of systemic and catheter-directed thrombolysis are discussed separately. (See "Acute pulmonary embolism in adults: Thrombolytic therapy in intermediate- and high-risk patients".)

Embolectomy — Emboli can be removed surgically or using a catheter-directed technique. The choice between these options depends upon available expertise, the presence or absence of a known diagnosis of PE, underlying comorbidities, and the anticipated response to such therapies. Further details on these techniques are provided separately. (See "Acute pulmonary embolism in adults: Thrombolytic therapy in intermediate- and high-risk patients", section on 'Catheter-directed therapies (CDTs)' and "Acute pulmonary embolism in adults: Thrombolytic therapy in intermediate- and high-risk patients", section on 'Surgical embolectomy'.)

SPECIAL POPULATIONS — 

The treatment of PE in special populations is discussed in separate topic reviews.

Patients with malignancy — (See "Anticoagulation therapy for venous thromboembolism (lower extremity venous thrombosis and pulmonary embolism) in adult patients with malignancy".)

Patients who are pregnant — (See "Anticoagulation during pregnancy and postpartum: Agent selection and dosing" and "Venous thromboembolism in pregnancy and postpartum: Treatment".)

Patients with heparin-induced thrombocytopenia — (See "Clinical presentation and diagnosis of heparin-induced thrombocytopenia" and "Management of heparin-induced thrombocytopenia".)

Inherited thrombophilias

●Factor V Leiden – (See "Factor V Leiden and activated protein C resistance", section on 'Patients with VTE'.)

●Prothrombin G20210A mutation – (See "Prothrombin G20210A", section on 'Patients with VTE'.)

●Protein S deficiency – (See "Protein S deficiency", section on 'Patients with VTE'.)

●Protein C deficiency – (See "Protein C deficiency", section on 'Thromboembolism management'.)

●Antithrombin deficiency – (See "Antithrombin deficiency", section on 'VTE treatment (hereditary deficiency)'.)

Antiphospholipid syndrome — (See "Antiphospholipid syndrome: Management".)

ADJUNCTIVE THERAPIES — 

Adjuncts include pain management and ambulation. Inferior vena cava filters are not routinely placed as an adjunct in patients with PE.

Pleuritic pain — When present, pleuritic pain from PE is best treated with scheduled medications, usually acetaminophen or nonsteroidal anti-inflammatories and occasionally narcotics. The choice among these agents should be individualized.

Ambulation — When feasible, early ambulation should be encouraged in most patients with acute PE, provided the patient is therapeutically anticoagulated. However, for those with significant clot burden especially in those with associated massive deep vein thrombosis, ambulation may be limited for the first 12 to 24 hours. Limited data suggest that rehabilitation is feasible in those with intermediate-risk PE, but has not been evaluated in high risk patients [74]. (See "Overview of the treatment of lower extremity deep vein thrombosis (DVT)", section on 'Ambulation'.)

COMPLICATIONS

Early complications (<3 months) — We consider early complications as those occurring within the first three months after the diagnosis of PE. The highest risk for events occurs within the first 7 to 14 days; death and morbidity during this period are most commonly due to shock and recurrent PE.

●Obstructive shock (ie, hemodynamic collapse) – Shock is an early complication of PE (8 percent of patients), especially in those with intermediate- and high-risk PE. It is the most common cause of early death and when present, is associated with a 30 to 50 percent mortality [24,25,75]. The risk remains elevated for 72 hours or more, thereby justifying close observation of those at greatest risk. (See "Acute pulmonary embolism in adults: Thrombolytic therapy in intermediate- and high-risk patients" and 'Embolectomy' above and 'Shock and right ventricular dysfunction' below.)

●Recurrence – The risk of recurrence is greatest in the first two weeks and declines thereafter. The cumulative proportion of patients with early recurrence while on anticoagulant therapy amounts to 2 percent at two weeks, and 6 percent at three months [76-78]. Predictors include cancer and subtherapeutic levels of anticoagulation, the management of which is discussed below [79,80]. (See 'Management of recurrence on therapy' below.)

●Pleuritis, alveolitis and pneumonia – In the one to two weeks following diagnosis, patients may deteriorate and develop worsening oxygenation, respiratory failure, hypotension, pain, and/or fever that suggests an evolving infarct and/or superimposed pneumonia.

Although chest radiography may reveal collapse, atelectasis, or a pleural effusion to support the presence of an evolving infarct and/or superimposed pneumonia, we reimage these (preferably with the original diagnostic imaging modality) to distinguish these diagnoses from recurrent PE.

Patients without recurrence should be treated symptomatically with supplemental oxygen, analgesics, and if indicated, intravenous fluids, ventilation, vasopressors, and/or antibiotics.

●Stroke – In patients with acute PE, there is an increased risk of stroke thought to be due to paradoxical embolism via a patent foramen ovale (PFO) [81-85]. Prevalence rates of stroke in patients with PE range from 7 to 50 percent (averaging <17 percent), with higher rates in those with PE who also have a PFO (21 to 64 percent, averaging <33 percent). In a prospective study of 361 patients with acute PE who underwent contrast-enhanced transthoracic echocardiography (TTE) and magnetic resonance imaging of the brain (for silent or symptomatic stroke) within ten days after the diagnosis of PE, stroke was diagnosed in 7.6 percent and PFO in 13 percent of patients [85]. Rates of stroke were higher in those who had a PFO compared with those who did not have a PFO (21.4 versus 5.5 percent).

We use a symptom-directed approach to search for a PFO when stroke occurs, rather than performing contrast TTE in all patients with PE.

Whether the discovery of a PFO with PE and stroke should prompt indefinite anticoagulation and/or PFO closure is also unknown such that a multidisciplinary approach with a pulmonologist, neurologist, and cardiologist is prudent.

Management of patients with stroke and PFO is discussed separately. (See "Patent foramen ovale" and "Initial assessment and management of acute stroke" and "Early antithrombotic treatment of acute ischemic stroke and transient ischemic attack" and "Long-term antithrombotic therapy for the secondary prevention of ischemic stroke".)

Late complications (>3 months) — Late events (ie, >3 months) following a diagnosis of PE occur in 9 to 32 percent of patients [1,4,86-89]. As examples:

●Recurrence – The cumulative rate of late recurrence has been reported to be 8 percent at six months, 13 percent at one year, 23 percent at five years, and 30 percent at 10 years [76-78]. However, in general, the rate is lowered with therapeutic anticoagulation and increased by the presence of select risk factors (eg, unprovoked PE, malignancy), which are discussed separately. (See "Selecting adult patients with lower extremity deep venous thrombosis and pulmonary embolism for indefinite anticoagulation".)

●Chronic thromboembolic disease (CTED) and chronic thromboembolic pulmonary hypertension (CTEPH) – CTED and CTEPH are unusual complications of PE that typically present with progressive dyspnea within two years of the initial event. The clinical manifestations and diagnosis of CTED and CTEPH are discussed separately. (See "Epidemiology, pathogenesis, clinical manifestations and diagnosis of chronic thromboembolic pulmonary hypertension".)

●Other – PE has been associated with an increased risk for subsequent cardiovascular events and atrial fibrillation [90]. (See "Overview of the causes of venous thrombosis in adults", section on 'Cardiovascular'.)

For most patients with dyspnea, exercise capacity and quality of life improve over the first year. Predictors of reduced quality of life and exercise capacity are female sex, higher body mass index, prior lung disease, and higher systolic pulmonary artery pressure on day 10 echocardiography [91].

PROGNOSIS

Mortality — PE-associated mortality is variable. Accurate estimates have been limited by data from heterogeneous populations of mixed risk and are mostly derived from older studies, registries, and hospital discharge records. However, in general, if left untreated, PE is associated with an overall mortality of up to 30 percent compared with 2 to 11 percent in those treated with anticoagulation [1,4,24,25,33,34,40,86,87,92].

Increased mortality appears to be maintained for many years following PE [1,88,89]. In one retrospective study of 1023 patients with PE, the five-year cumulative mortality rate was 32 percent [89]. Among those who died, only 5 percent of the deaths were due to recurrent PE, 64 percent were due to noncardiovascular causes (eg, malignancy, sepsis), and 31 percent were due to cardiovascular causes other than PE (eg, myocardial infarction, heart failure, and stroke). Another database analysis of over 128,000 patients reported a threefold increase in mortality at 30 years in patients with PE when compared with age- and sex-matched controls who did not have PE during the same period [88].

PE-related mortality may be decreasing with reported rates falling from 3.3 percent (2001 to 2005) to 1.8 percent (2010 to 2013) in one study and from 17 to 10 percent in another study [92,93]. The World Health Organization (WHO) mortality database reported a similar decrease in deaths from 12.8 per 100,000 to 6.6 per 100,000 between 2000 and 2015 [94].

Prognostic factors — Poor prognostic factors in patients diagnosed with PE are discussed in the sections below.

Shock and right ventricular dysfunction — In patients with PE, several clinical, radiologic, and laboratory markers of right ventricular (RV) dysfunction have been identified as poor prognosticators.

●Clinical – The presence of cardiogenic shock, which is due to severe RV failure, consistently predicts death in patients diagnosed with PE, the details of which are discussed above. (See 'Early complications (<3 months)' above.)

●RV dysfunction – RV dysfunction, assessed by echocardiography or CT pulmonary angiography, is associated with increased mortality [95-102].

RV dysfunction may also predict recurrent venous thromboembolism (VTE). In one prospective observational study of 301 patients with PE, those with persistent RV dysfunction on echocardiography at three months following diagnosis had a fourfold increased risk of recurrent VTE when compared with patients without RV dysfunction or with patients whose RV dysfunction resolved prior to discharge (9 versus 3 and 1 percent patient-years) [103]. Echocardiographic findings of RV dysfunction in patients with PE are discussed separately. (See "Clinical presentation and diagnostic evaluation of the nonpregnant adult with suspected acute pulmonary embolism", section on 'Echocardiography' and "Echocardiographic assessment of the right heart", section on 'Conditions associated with right ventricular pathology'.)

●Laboratory – Elevated biochemical markers of RV dysfunction at diagnosis have consistently been associated with an increased risk of death or other adverse outcomes in patients with PE (eg, elevated brain natriuretic peptide [BNP], N-terminal pro-BNP, and troponin) [95,104-113]. However, the optimal cutoff values for risk stratification are unknown. In hemodynamically stable patients, these markers are poor predictors of death when elevated but consistently identify a benign clinical course when normal or low [97,105,108,109,111,113-116].

Right ventricle thrombus — Mobile right heart thrombi are seen in approximately 4 percent of patients with PE, by either echocardiography or CT, and the proportion is higher among patients who are critically ill (up to 18 percent) [117,118]. The presence of right heart thrombus has been shown in several studies to be associated with RV dysfunction and high early mortality [117,119,120]. As an example, data from an international registry of patients with PE reported that, compared with patients without RV thrombus, patients with RV thrombus had a higher 14-day mortality (21 versus 11 percent) and three-month mortality (29 versus 16 percent) [117]. Management of clot-in-transit is discussed separately. (See "Acute pulmonary embolism in adults: Thrombolytic therapy in intermediate- and high-risk patients", section on 'Clot-in-transit'.)

Deep vein thrombosis — Patients with PE and a coexisting deep vein thrombosis (DVT) are at increased risk for death. As an example, one prospective study of 707 patients with acute PE reported that, at three months, patients with concomitant DVT had an increased all-cause mortality (adjusted hazard ratio [HR] 2.05, 95% CI 1.24-3.38) and PE-specific mortality (adjusted HR 4.25, 95% CI 1.61-11.25) compared with those without concomitant DVT [49].

Other — Additional predictors of poor prognosis that require further validation include the following:

●Hyponatremia (<130 mmol/L) and indicators of kidney dysfunction [121-123]

●Serum lactate (>2 mmol/L) [124,125]

●White blood cell count (>12.6 x 10⁹/L) [126]

●The Charlson comorbidity index ≥1 [127]

●Residual pulmonary vascular obstruction [128,129]

●Age ≥65 years [130]

●Poor adherence to guidelines [131]

●Tachycardia on admission [132]

●Acute kidney injury [133]

Prognostic models — Prognostic models can facilitate risk stratification (see 'Assess mortality risk (low, intermediate, high)' above) and the identification of those suitable for outpatient therapy. (See 'Outpatient anticoagulation' above.)

Several prognostic models have been derived in patients with acute PE, among which the Pulmonary Embolism Severity Index (PESI) and the simplified PESI (sPESI) are the most well-known (table 4) [134-138]. While PESI and sPESI predict death and are the most common models used, newer composite models may predict death and/or complications (recurrent PE, hemodynamic collapse). While many of the available prognostic models are sensitive in predicting death from acute PE, they are not specific [139].

As examples:

●PESI – The PESI adds the patient's age to points assigned to ten additional variables (table 4) [134]: The total score categorizes the patient according to increasing risk for mortality:

•Class I (<66 points)

•Class II (66 to 85 points)

•Class III (86 to 105 points)

•Class IV (106 to 125 points)

•Class V (>125 points)

Patients with class I/II are considered to be at low risk of death while those with classes III through V are at high risk. The major limitation of PESI is that it is difficult to apply in a busy clinical setting because so many variables must be considered, each with its own weight.

●sPESI – The sPESI (table 4) is a modified version of PESI that is less cumbersome [140]. A score of zero indicates a low risk for mortality while a score of one or more indicates a high risk.

The sPESI may have a prognostic accuracy that is similar to PESI. In a cohort of 995 patients with PE that compared PESI with sPESI, a similar 30-day mortality was reported in patients classified as low risk (3 versus 1 percent) or high risk (11 percent each) [140].

●Other – A composite model ("Protect score") that incorporates sPESI, BNP, cardiac troponin I, and lower limb ultrasonography (done within 48 hours of admission) was derived and validated in a cohort of 848 normotensive patients with acute PE [137]. Another score ("BOVA score") has also been described [141]. However, further validation of these models is required before they can be routinely applied in clinical practice.

MONITORING AND FOLLOW-UP — 

Patients with PE should be monitored following diagnosis for the following:

●Therapeutic levels of anticoagulation – The most common laboratory test used to monitor unfractionated heparin is the activated partial thromboplastin time. Warfarin is monitored using the prothrombin time ratio, usually expressed as the international normalized ratio. (See "Biology of warfarin and modulators of INR control" and "Warfarin and other VKAs: Dosing and adverse effects" and "Heparin and LMW heparin: Dosing and adverse effects".)

Low molecular weight heparin, fondaparinux, and direct oral anticoagulants do not require routine laboratory monitoring. (See "Direct oral anticoagulants (DOACs) and parenteral direct-acting anticoagulants: Dosing and adverse effects".)

The development of conditions that affect the half-life of the anticoagulant used (eg, kidney failure, pregnancy, weight gain/loss, drug interactions) should also be followed.

●Complications of PE – At each visit, patients should be monitored for continued resolution of the presenting manifestations of PE and investigated for new symptoms suggestive of recurrent PE or deep vein thrombosis [142,143]. The development of persistent or progressive dyspnea, particularly during the first three months to two years of diagnosis, may suggest the development of chronic thromboembolic disease (CTED) or chronic thromboembolic pulmonary hypertension (CTEPH; affects up to 5 percent of patients).

While most clinicians do not routinely perform follow-up PE imaging, clinicians should have a low threshold to repeat diagnostic imaging if recurrence or CTEPH is suggested. The diagnosis and management of recurrence and CTEPH are discussed separately. (See 'Management of recurrence on therapy' below and "Clinical presentation and diagnostic evaluation of the nonpregnant adult with suspected acute pulmonary embolism" and "Epidemiology, pathogenesis, clinical manifestations and diagnosis of chronic thromboembolic pulmonary hypertension" and "Chronic thromboembolic pulmonary hypertension: Initial management and evaluation for pulmonary artery thromboendarterectomy".)

In some institutions, specialty clinics follow patients with PE (eg, "clot clinic") to ensure adequate and thorough follow-up and may be valuable in detecting CTED/CTEPH [143].

●Complications of the therapy – Patients should be monitored for complications including bleeding (anticoagulants), skin necrosis (warfarin), osteoporosis (heparin), thrombocytopenia (heparin), and device migration (cava filters). Details regarding the individual complications of such therapies are discussed separately. (See "Heparin and LMW heparin: Dosing and adverse effects" and "Warfarin and other VKAs: Dosing and adverse effects" and "Direct oral anticoagulants (DOACs) and parenteral direct-acting anticoagulants: Dosing and adverse effects" and "Placement of vena cava filters and their complications", section on 'Complications'.)

●The need for indefinite anticoagulation – The indications for indefinite anticoagulation are discussed separately. (See "Selecting adult patients with lower extremity deep venous thrombosis and pulmonary embolism for indefinite anticoagulation".)

●The need for device removal – Patients who had an inferior vena cava filter placed because anticoagulation was contraindicated should initiate anticoagulant therapy once the contraindication has resolved and have the filter retrieved, if feasible. (See "Placement of vena cava filters and their complications", section on 'Filter retrieval'.)

●The underlying predisposing risk factors for PE – The presence or absence of risk factors that predisposed the patient to the development of PE (eg, malignancy, inherited thrombotic disorder, surgery) should be sought and investigated, as indicated. The evaluation of patients with established venous thromboembolism for risk factors is discussed separately. (See "Evaluating adult patients with established venous thromboembolism for acquired and inherited risk factors".)

MANAGEMENT OF RECURRENCE ON THERAPY — 

Reasons for recurrence while on therapy include the following, among which inadequate anticoagulation is the most common:

●Subtherapeutic anticoagulation – We perform a detailed history and examination to identify factors that contribute to subtherapeutic anticoagulation including the following:

•Malabsorption (eg, malabsorption syndromes, rivaroxaban not being taken with food) (see "Overview of nutrient absorption and etiopathogenesis of malabsorption")

•Discontinuation for an anticipated procedure (see "Perioperative management of patients receiving anticoagulants")

•Poor compliance

•Altered dose requirement or pharmacokinetics for warfarin (eg, dietary vitamin K), direct oral anticoagulants (DOACs; eg, drug interactions, kidney injury), or low molecular weight heparin (eg, weight gain)

•High dose requirement for heparin (eg, increased heparin binding proteins, aprotinin)

•Incorrect dosing of medication

Consulting a coagulation specialist may be warranted, especially when abnormal pharmacokinetics or noncompliance for medications that cannot be monitored easily are suspected (eg, DOACs, LMW heparin). (See "Heparin and LMW heparin: Dosing and adverse effects", section on 'Heparin resistance/antithrombin deficiency' and "Direct oral anticoagulants (DOACs) and parenteral direct-acting anticoagulants: Dosing and adverse effects" and "Biology of warfarin and modulators of INR control".)

For those who are subtherapeutic on unfractionated heparin (UFH), the dose should be increased to rapidly achieve therapeutic levels. For patients who are on LMW heparin or DOACs in whom subtherapeutic anticoagulation is suspected but unconfirmed or for those subtherapeutic on warfarin, switching to a rapid-acting anticoagulant that can be followed, such as UFH, may be prudent while investigations are ongoing.

●Suboptimal therapy – Suboptimal therapies include inferior vena cava (IVC) filters, embolectomy, or thrombolysis not followed by anticoagulation, most of which should be apparent to the investigating clinician. When feasible, therapeutic anticoagulation should be considered in such cases.

●Ongoing prothrombotic stimuli – In patients who develop recurrence despite therapeutic anticoagulation, a search for conditions associated with high recurrence rates is prudent. These include malignancy, May-Thurner syndrome, inherited thrombotic disorders (eg, protein S, protein C, or antithrombin deficiency), and antiphospholipid syndrome. (See "Evaluating adult patients with established venous thromboembolism for acquired and inherited risk factors" and "Overview of the causes of venous thrombosis in adults", section on 'Anatomic risk factors for deep vein thrombosis'.)

In this population, therapeutic options are limited. We suggest an approach similar to that performed in patients with recurrent thrombosis who have an underlying malignancy. Further details regarding these strategies are discussed separately. (See "Antiphospholipid syndrome: Management", section on 'Recurrent thromboembolism despite adequate anticoagulation' and "Anticoagulation therapy for venous thromboembolism (lower extremity venous thrombosis and pulmonary embolism) in adult patients with malignancy", section on 'Management of recurrence'.)

Other rare conditions promote thrombus propagation (eg, mechanical obstruction of venous flow from pelvic masses or IVC filter) or thrombus dissociation (eg, large right ventricular [144] or valvular thrombus). In such patients, treating the underlying cause or removing mobile thrombus is appropriate, when feasible.

●Misdiagnosis – Occasionally, tumor or fat emboli may radiographically mimic PE due to thrombus, the presentation and management of which are discussed separately. (See "Pulmonary tumor embolism and lymphangitic carcinomatosis in adults: Diagnostic evaluation and management" and "Fat embolism syndrome".)

SOCIETY GUIDELINE LINKS — 

Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Superficial vein thrombosis, deep vein thrombosis, and pulmonary embolism".)

INFORMATION FOR PATIENTS — 

UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Basics topics (see "Patient education: Pulmonary embolism (blood clot in the lung) (The Basics)")

●Beyond the Basics topics (see "Patient education: Pulmonary embolism (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

●Initial resuscitation – Our approach is the following (table 1):

•Supplemental oxygen should be administered to target an oxygen saturation ≥90 percent. When mechanical ventilation is necessary, an expert in cardiovascular anesthesia should perform intubation to avoid catastrophic hypotension due to sedation and positive pressure ventilation. Unstable patients with severe hypoxemia, respiratory failure, and/or hemodynamic instability require management by critical care and airway experts. (See 'Respiratory support' above.)

•For patients with pulmonary embolism (PE) who are hypotensive, we suggest small-volume bolus infusions of intravenous fluid (eg, 250 to 500 mL of normal saline) rather than larger volumes (eg, 2 to 3 L) (Grade 2C). Large volumes of intravenous fluid can worsen hypotension in those with PE-related right ventricular (RV) dysfunction. When two to three smaller boluses of intravenous fluid fail, vasopressor therapy should be initiated. (See 'Hemodynamic support' above.)

●Assess mortality risk – Risk assessment includes an evaluation of RV function using CT pulmonary angiography and/or echocardiography and laboratories (troponin and brain natriuretic peptide [BNP]). PE-associated mortality should be assessed as low- (most patients), intermediate-, or high-risk (table 3 and table 4). For intermediate- and high-risk patients, PE response teams (PERTs), when available, should be consulted to guide therapy and identify those that may need specialized therapies (eg, thrombolysis, catheter-directed therapies, surgical embolectomy). Depending on center capabilities, transfer to another hospital may be required for more advanced procedures when indicated. (See 'Assess mortality risk (low, intermediate, high)' above.)

Empiric anticoagulation – For patients with a high pretest probability (PTP) (calculator 1) and a risk of bleeding that is not high, we suggest immediate empiric anticoagulation pending diagnostic imaging (Grade 2C). In such cases, the benefit of preventing further PE outweighs the risk of bleeding. Empiric anticoagulation may also be appropriate for patients with low or intermediate PTP when diagnostic imaging is delayed. Anticoagulant therapy is not administered to those with contraindications or with an unacceptably high risk of bleeding; the diagnostic evaluation should be expedited, when feasible. (See 'Empiric anticoagulation or thrombolysis' above.)

●Hemodynamically stable low-risk PE – Low-risk PE has a simplified Pulmonary Embolism Severity Index (sPESI) score of 0 and is not associated with RV dysfunction or hypotension (table 3). In such patients, we base treatment on bleeding risk (see 'Low-risk PE' above):

•Bleeding risk not high – For most stable patients with low-risk PE and a bleeding risk that is not high, we recommend immediate anticoagulant therapy (Grade 1B). Anticoagulation reduces the risk of further embolization and PE-related death. Details regarding agent selection (table 6) and duration are provided separately. (See 'Anticoagulation' above and "Venous thromboembolism: Initiation of anticoagulation" and "Venous thromboembolism: Anticoagulation after initial management".)

•Contraindications anticoagulation – For patients with contraindications to anticoagulation or an unacceptably high bleeding risk, we suggest prompt placement of a retrievable inferior vena cava (IVC) filter (Grade 2C). IVC filters can prevent PE recurrence. Anticoagulation should be administered and the filter removed once the contraindication resolves. (See 'Contraindications to anticoagulation: Inferior vena cava filter' above.)

Subsegmental PE is treated similarly. However, those with a single small defect and no evidence of thrombus elsewhere may reasonably opt for no anticoagulation, provided the risk of recurrence is low (eg, provoked PE, lack of persistent factors, single defect) and they are monitored with serial compression ultrasonography at two weeks. (See 'Patients with subsegmental PE' above.)

Outpatient anticoagulation is safe and effective in select patients at low risk of death (table 4), as assessed by all of the factors listed in the table (table 7). (See 'Outpatient anticoagulation' above.)

●Intermediate-risk/submassive PE – Intermediate-risk PE is associated with elevated PESI score, biochemical (BNP, troponin), echocardiographic, and/or imaging evidence of RV dysfunction without systemic hypotension (table 3).

•Most patients with intermediate-risk PE should be treated the same as low-risk patients (ie, anticoagulant therapy or, if contraindicated or the risk of bleeding is unacceptably high, an IVC filter). In addition, expert consultation should be obtained to identify patients who may benefit from thrombolytic therapy or thrombectomy; these may include patients on the higher end of the intermediate-risk spectrum. Patients should be monitored closely for deterioration. (See 'Anticoagulation' above and "Acute pulmonary embolism in adults: Thrombolytic therapy in intermediate- and high-risk patients", section on 'Catheter-directed thrombolysis'.)

●Hemodynamically unstable/high-risk PE – Patients with high-risk PE include those with hypotension, shock, or cardiac arrest due to PE. Hypotension is defined as any one of the following: systolic blood pressure (BP) <90 mmHg; requires vasopressors or inotropic support; persistent despite resuscitation; or a drop in systolic BP of ≥40 mmHg from baseline for >15 minutes. Hypotension is unexplained by other etiologies.

Patients with high-risk PE who are at low risk of bleeding are usually treated with systemic thrombolytic therapy (table 8) followed by anticoagulation, necessitating consultation by a subspecialist (eg, pulmonologist, cardiologist, emergency department, critical care physician, or PERT). Thrombolysis results in faster hemodynamic resolution compared with heparin but is associated with an increased risk of major and sometimes catastrophic bleeding.

Further details regarding thrombolysis in this population are provided in a separate topic review. (See "Acute pulmonary embolism in adults: Thrombolytic therapy in intermediate- and high-risk patients" and 'Thrombolytic therapy' above.)

●Complications – Complications of acute PE include cardiogenic shock, recurrence, pneumonia, stroke, and chronic thromboembolic disease or chronic thromboembolic pulmonary hypertension. (See 'Complications' above.)

●Prognosis – Death, most commonly from cardiogenic shock or arrhythmias, occurs in 4 to 13 percent and (if untreated) 30 percent. The highest risk occurs within the first 7 to 14 days, with death most commonly due to shock. Prognostic models that incorporate clinical findings (eg, PESI and sPESI (table 4)) and/or biochemical markers that indicate RV strain can predict early death and/or recurrence. (See 'Prognosis' above.)

●Management of recurrence – Inadequate anticoagulation is the most common reason for recurrent venous thromboembolism while on therapy. The clinician should test for therapeutic levels of anticoagulants, when relevant, as well as consider additional etiologies of recurrence (eg, suboptimal therapy, ongoing prothrombotic stimuli, and alternate diagnoses). Further details are provided separately. (See 'Management of recurrence on therapy' above and "Antiphospholipid syndrome: Management", section on 'Recurrent thromboembolism despite adequate anticoagulation' and "Anticoagulation therapy for venous thromboembolism (lower extremity venous thrombosis and pulmonary embolism) in adult patients with malignancy", section on 'Management of recurrence'.)

ACKNOWLEDGMENT — 

The UpToDate editorial staff acknowledges Victor F Tapson, MD, who contributed to earlier versions of this topic review.