ALG Pulmonary Embolism 1161

• More than 90% of pulmonary emboli origi-
BASIC INFORMATION
DEFINITION
Pulmonary embolism (PE) refers to the lodging
of a thrombus or other embolic material from
a distant site in the pulmonary circulation. A
classification of acute pulmonary embolism is
described in Table 1.
SYNONYMS
Pulmonary thromboembolism
8. Visceral cancer (lung, pancreas, alimen-
nate in the deep venous system of the lower
extremities.
• Pulmonary thromboembolism is associated
with >200,000 hospitalizations. 8% to 10%
of victims of PE die within the first hr.
PHYSICAL FINDINGS & CLINICAL
PRESENTATION
• Most common symptom: dyspnea (82%-85%).
• Tachypnea (30%-60%).
• Cough (30%-40%)
• Wheezing (20%)
tary and genitourinary tracts).
9. Spinal cord injury.
P
10. Advanced age.
11. Obesity.
12. Hematologic disease (e.g., factor V Leiden
mutation, antithrombin III deficiency, pro-
tein C deficiency, protein S deficiency,
lupus anticoagulant, polycythemia vera,
dysfibrinogenemia, paroxysmal noctur-
nal hemoglobinuria, acquired protein
C resistance without factor V Leiden,
G20210A prothrombin mutation).

and Disorders
Diseases
PE
• Chest pain: may be nonpleuritic or pleuritic 13. COPD, diabetes mellitus, acute medical
ICD-10CM CODES (infarction) (40%-49%). illness.
I26 Pulmonary embolism • Syncope (massive PE) (10%-14%). 14. Prolonged air travel.
I26.01 Septic pulmonary embolism with • Fever, diaphoresis, apprehension. 15. Central venous catheterization.
acute cor pulmonale • Hemoptysis (2%). 16. Autoimmune diseases (SLE, IBD, RA).
126.09 Other pulmonary embolism with
acute cor pulmonale
• Evidence of DVT may be present (e.g., swell-
ing and tenderness of extremities). I
126.90 Septic pulmonary embolism with- • Cardiac examination may reveal: tachycardia DIAGNOSIS
out acute cor pulmonale (23%), increased pulmonic component of
126.99 Other pulmonary embolism without S2, murmur of tricuspid insufficiency, right DIFFERENTIAL DIAGNOSIS
acute cor pulmonale ventricular heave, right-sided S3. • Myocardial infarction.
127.82 Chronic pulmonary embolism • Pulmonary examination: may demonstrate • Pericarditis.
Z86.711 Personal history of pulmonary rales, localized wheezing, friction rub. • Pneumonia.
embolism • Pneumothorax.
ETIOLOGY • Chest wall pain.
EPIDEMIOLOGY & • Thrombus, fat, or other foreign material • GI abnormalities (e.g., peptic ulcer, esopha-
DEMOGRAPHICS • Risk factors for PE: geal rupture, gastritis.
• 650,000 cases of PE occur in the U.S. each 1.  Prolonged immobilization, reduced • CHF.
year (increased incidence in women and mobility. • Pleuritis.
with advanced age); annually, as many as 2. Postoperative state, major surgery. • Anxiety disorder with hyperventilation.
100,000 people in the U.S. die from acute 3. Trauma to lower extremities, immobi- • Pericardial tamponade.
PE, and the diagnosis is often not made lizer, or cast. • Dissection of aorta.
until after autopsy. The incidence of PE is 4.  Estrogen-containing birth control pills, • Asthma.
increasing with the increasing use of spiral hormone replacement therapy.
CT scans, with a lower severity of illness and 5. Prior history of DVT or PE. WORKUP
lower mortality, suggesting the increase is 6. CHF. • Clinical assessment alone is insufficient to
caused by earlier diagnosis. 7. Pregnancy and early puerperium. diagnose or rule out PE. It is also important
to remember that no single noninvasive test
has both high sensitivity and high specificity
for PE. Consequently, in addition to clinical
assessment, most patients require an imag-
TABLE 1  Classification of Acute Pulmonary Embolism ing test to diagnose PE. An integrated diag-
nostic approach to PE is illustrated in Fig. 1.
Category The Wells prediction rules (Table 2) and the
(Frequency) Presentation Therapy revised Geneva score (Table 3) can be used
Massive PE Systolic blood pressure <90 mm Hg Anticoagulation (usually starting with intra- to estimate the probability of PE. In the Wells
(5%-10%) or poor tissue perfusion or venous UFH), plus consider advanced prediction rules, each of the following find-
multisystem organ failure plus therapy: systemic thrombolysis, pharma- ings is assigned a score:
extensive thrombosis, such as comechanical catheter-directed therapy, 1.  Clinical signs/symptoms of deep vein
“saddle” PE or right or left main surgical embolectomy, or inferior vena thrombosis (score = 3.0).
pulmonary artery thrombus cava (IVC) filter 2. No alternate diagnosis as likely or more
Submassive PE Hemodynamically stable but mod- Anticoagulation usually with intravenous UFH likely than PE (score = 3.0).
(20%-25%) erate or severe right ventricular until decision made regarding implemen- 3. Heart rate >100/min (score = 1.5).
dysfunction or enlargement, tation of advanced therapy; controversy
coupled with biomarker eleva- centers on this group. For systemic throm-
4. Immobilization or surgery in last 4 weeks
tion indicative of right ventricu- bolysis, reducing the rate of cardiovascular (score = 1.5).
lar microinfarction and/or right collapse and death must be balanced 5. Previous history of DVT or PE (score =
ventricular pressure overload against the increased rate of hemorrhagic 1.5).
stroke. 6. Hemoptysis (score = 1.0).
For patients at low bleeding risk with severe 7.  Cancer actively treated within last 6
right ventricular dysfunction, consider months (score = 1.0).
same interventions as for massive PE • The probability of PE is high if total score is
Small to moderate Normal hemodynamics and normal Anticoagulation with parenteral therapy as >6, moderate if 2-6; and low if <2.
PE (70%) right ventricular size and func- a bridge to warfarin or, alternatively, with • The modified Wells score divides PE as likely
tion oral rivaroxaban regimen as monotherapy (>4 points) or unlikely (<4 points).
UFH, Unfractionated heparin. • A low clinical probability of PE in association
From Mann DL et al: Braunwald’s heart disease, ed 10, Philadelphia, 2015. Elsevier. with a normal plasma D-dimer measurement

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1162 Pulmonary Embolism ALG

Suspect pulmonary embolism • Serial compressive duplex ultrasonography

of lower extremities can be used in patients
with “low-probability” lung scan and high
clinical suspicion (see “Imaging Studies”). It
History, exam, oximetry, CXR, ECG
is useful if positive; negative results do not
exclude PE.
Assess clinical likelihood of PE LABORATORY TESTS
• ABGs may reveal hypoxemia and respirato-
ry alkalosis (decreased Pao2 and Paco2 and
increased pH); normal results do not rule out PE.
Non-high High clinical
• Alveolar-arteriolar (A-a) oxygen gradient, a
clinical probability probability
measure of the difference in oxygen con-
centration between alveoli and arterial blood,
may be elevated. However, a normal A-a
D-dimer gradient does not rule out PE.
• High-sensitivity plasma D-dimer measure-
ment: D-dimer assays by ELISA detect the
presence of plasmin-mediated degradation
Normal High Chest CT
products of fibrin that contain cross-linked
D fragments in the whole blood or plasma.
A normal plasma D-dimer level is useful to
No pulmonary Normal Positive exclude PE in patients with a low pretest
embolism probability of PE. However, it cannot be used
to “rule in” the diagnosis because it increas-
No pulmonary Treat for es with many other disorders (e.g., meta-
embolism pulmonary static cancer, trauma, sepsis, postoperative
embolism state). Plasma D-dimer can also be used in
conjunction with lower-extremity compres-
FIG. 1  Integrated diagnostic approach. CXR, chest x-ray [examination]. (From Mann DL et al: Braunwald’s sion ultrasonography in patients with indeter-
heart disease, ed 10, Philadelphia, 2015. Elsevier.) minate V/Q and spiral CT scans. Absence of
DVT and presence of a normal D-dimer level
in these settings generally rules out clinically
TABLE 2  Wells Score for TABLE 3  Revised Geneva Score significant PE.
Pulmonary Embolism* for Pulmonary Embolism* • Elevated cardiac troponin levels also occur in
patients with PE because of right ventricular
Characteristic Points Characteristic Points dilation and myocardial injury; therefore,
PE should be considered in the differential
Risk Factors Risk Factors
diagnosis of all patients presenting with
Previous pulmonary embolism or 1.5 Age >65 yr 1 chest pain or dyspnea and elevated cardiac
deep venous thrombosis Previous pulmonary embolism or 3 troponin levels.
Immobilization or surgery in the 1.5 deep venous thrombosis • Elevated serum BNP levels in patients with
previous 4 wk Surgery (under general anesthesia) or 2 acute PE may reflect RV overload. The patho-
Cancer 1 fracture (of lower limbs) within 1 mo physiology of RV dysfunction in PE is illus-
Clinical Findings Cancer (active or considered cured 2 trated in Fig. 3.
Hemoptysis 1 <1 yr) • ECG is abnormal in 85% of patients with
Heart rate >100/min 1.5 Clinical Findings acute PE. Frequent abnormalities are sinus
Clinical signs of deep venous 3 Unilateral leg pain 3 tachycardia; nonspecific ST-segment or
thrombosis Hemoptysis 2 T-wave changes; S-1, Q-3, T-3 pattern (10%
Other Heart Rate of patients); S-1, S-2, S-3 pattern; T-wave
Alternative diagnosis is less likely 3 75-94 beats/min 3 inversion in V1 to V6; acute RBBB; new-onset
than pulmonary embolism ≥95 beats/min 5 atrial fibrillation; ST segment depression in
Pain on palpation of lower-limb deep 4 lead II; right ventricular strain. A right ven-
Interpretation of total score: 0-1 point, low probability; 2-6 tricular strain pattern on ECG in patients with
points, moderate probability; 7 or more points, high prob- veins and unilateral edema
ability. PE and normal blood pressure is associated
*Wells PS et al: Derivation of a simple clinical model to cate- Interpretation of total score: 0-3 points, low probability; with adverse short-term outcome and adds
gorize patients probability of pulmonary embolism: in- 4-10 points, moderate probability; ≥11 points, high incremental prognostic value to echocardio-
creasing the models utility with the SimpliRED D-dimer, probability.
*Le Gal G et al: Prediction of pulmonary embolism in the
graphic evidence of right ventricular function.
Thromb Haemost 83:416–420, 2000.
From McGee S: Evidence-based physical diagnosis, ed 4, emergency department: the revised Geneva score, Ann
Philadelphia, 2018, Elsevier. Intern Med 144:165–171, 2006. IMAGING STUDIES
From McGee S: Evidence-based physical diagnosis, ed 4, • Chest x-ray may be normal; suggestive find-
Philadelphia, 2018, Elsevier.
essentially rules out PE, and further imag- ings include elevated diaphragm, pleural
ing is not needed. If clinical probability is effusion, dilation of pulmonary artery, infil-
intermediate or high, and/or the D-dimer • V/Q scan is reserved for patients with clini- trate or consolidation, abrupt vessel cut-off,
measurement is abnormal, further workup cally significant contrast allergies or renal oligemia distal to the PE (Westermark sign),
with imaging is needed. insufficiency, or when CTPA is not available. or atelectasis. A wedge-shaped consolidation
• CT pulmonary angiography (CTPA) (see Fig. 2) • Pulmonary angiogram (gold standard) can in the middle and lower lobes is suggestive
is an excellent diagnostic modality (83% confirm the diagnosis in equivocal cases, but of a pulmonary infarction and is known as
sensitivity and 96% specificity). is rarely used. Hampton’s hump.

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 ALG Pulmonary Embolism 1163

A B C

and Disorders
Diseases
FIG. 2  A 46-year-old woman presented with acute shortness of breath and hypoxia. Chest
radiograph was normal. A, Chest computed tomography shows a low-attenuation filling defect in left and
right main pulmonary arteries (arrows) and left upper lobe segmental artery (arrow), representing massive
pulmonary embolism. Emboli extend to left and right interlobar arteries (arrows), as well as a left lower lobe
segmental artery (arrow), seen in B and C, respectively. (From Vincent JL et al: Textbook of critical care, ed 6,
Philadelphia, 2011, Saunders.) I
Pulmonary embolism

Anatomic Neurohumoral
obstruction effects

PA pressure
RV afterload RV wall tension

RV O2 demand

RV dilation/dysfunction RV ischemia

RV output Interventricular RV O2 supply

septal shift to LV

Coronary
LV preload perfusion

Systemic perfusion
LV output Hypotension

Systemic perfusion

FIG. 3  Pathophysiology of right ventricular dysfunction and its deleterious effects of causing decreased sys-
temic arterial pressure, decreased coronary perfusion, and deteriorating ventricular function. LV, Left ventricle/
ventricular; PA, pulmonary artery; RV, right ventricle/ventricular. (From Mann DL et al: Braunwald’s heart dis-
ease, ed 10, Philadelphia, 2015. Elsevier.)

• CT angiography is an accurate, noninvasive
tool in the diagnosis of PE at the main, lobar,
and segmental pulmonary artery levels. A
major advantage of CT angiography over
standard pulmonary angiography is its ability
to diagnose intrathoracic disease other than
PE that may account for the patient’s clinical
picture. It is also less invasive, less costly, and
more widely available. Its major shortcoming
is its poor sensitivity for subsegmental emboli.
• V/Q Lung scan (in patient with normal chest
x-ray examination): This test must be inter-
preted within the pretest probability of having
a PE.
1. A normal lung scan rules out PE.
2. A ventilation-perfusion mismatch is sug-
gestive of PE, and a lung scan interpreta-
tion of high probability is confirmatory
(Fig. E4).
3. If the clinical suspicion of PE is high and
the lung scan is interpreted as low prob-
ability, moderate probability, or indeter-
minate, a pulmonary arteriogram is diag-
nostic; a positive arteriogram confirms
diagnosis; a positive compressive duplex
ultrasonography for DVT obviates the
need for an arteriogram, because treat-
ment with IV anticoagulants is indicated
in these patients; the overall sensitivity of
compressive ultrasonography for DVT in
patients with PE is 29%, specificity 97%;
adding ultrasonography in patients with
a nondiagnostic lung scan prevents 9%
of angiographies; however, this improve-
ment in efficacy is achieved at the cost
of unnecessary anticoagulant therapy in
26% of patients who have false-positive
ultrasonography results.
• Angiography: pulmonary angiography is the
historic gold standard; however, it is invasive,
expensive, and not readily available in some
clinical settings. False-positive pulmonary

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1164 Pulmonary Embolism ALG

angiograms may result from mediastinal dis-
orders such as radiation fibrosis and tumors.
• 
Gadolinium-enhanced magnetic resonance
angiography (MRA/MRV) of the pulmonary
arteries has a moderate sensitivity and high
specificity for the diagnosis of PE at expe-
rienced centers, but obtaining acceptable
images is technically challenging and should
only be performed if other imaging tests are
contraindicated.
• 
Echocardiography: useful for identifying
patients with PE who may have poor progno-
sis. Moderate or severe hypokinesis, persis-
tent pulmonary hypertension, patent foramen
ovale, and free-floating right heart thrombus
are markers for increased risk of death or
recurrent thrombosis. Such patients should be
considered for thrombolysis or embolectomy.
TREATMENT
NONPHARMACOLOGIC THERAPY
Correction of risk factors (see “Etiology”) to
prevent future PE.
ACUTE GENERAL Rx
Patients with acute PE should be initially strati-
fied according to risk (Table 1) so that higher-
risk therapies (e.g., thrombolysis, embolectomy)
are offered to patients with the greatest chance
of benefit.
• Anticoagulants are recommended as initial
therapy in patients with small to moderate PE.
• Anticoagulant drugs for initial treatment of PE
are described in Table 4. Unfractionated hepa-
rin (UFH) (IV or subcutaneous), subcutaneous
low-molecular-weight heparin (LMWH), or
subcutaneous fondaparinux is recommended
for the initial treatment for at least 5 days.
If IV unfractionated heparin is used, a bolus
dose (80 U/kg) followed by a weight-based
(18 U/kg/hr) continuous infusion to achieve
therapeutic anti-factor Xa (or aPTT) levels
should be used. LMWH and fondaparinux
should be avoided in patients with severe
renal failure.
• Oral rivaroxaban, a factor Xa inhibitor (15 mg
bid for 3 wk, then 20 mg/d), has been studied
as a treatment for DVT and for PE, without
prior parenteral therapy. For both DVT and
PE, treatment with rivaroxaban alone was
noninferior to treatment with LMWH followed
by a vitamin K antagonist with regard to the
endpoint of recurrent venous thromboembo-
lism. Use of rivaroxaban should be avoided in
patients with severe renal failure.
• Dabigatran, a direct thrombin inhibitor (150
mg twice a day), has been approved for the
treatment of PE from data assembled from
the RECOVER, REMEDYSM, and RESONATE
trials. Dabigatran met its noninferiority effi-
cacy endpoints with improved safety margins
(bleeding) compared to warfarin. All trial
recipients received heparin bridge to start
their anticoagulation.
• Apixaban, a Factor Xa inhibitor (10 mg twice
a day for a week, followed by 5 mg twice a
day), is also approved for the treatment of
acute PE based on the data in the AMPLIFY
and AMPLIFY-EXT trials, in which apixa-
ban met its noninferiority mark in terms of
efficacy and improved safety compared to
warfarin.
• Thrombolytic agents (urokinase, tPA, strep-
tokinase): provide rapid resolution of clots
with increased risk of major bleeding (up to
3% incidence of intracranial hemorrhage);
thrombolytic agents are the treatment of
choice in patients with massive PE who
are hemodynamically unstable and with no
contraindication to their use. Fig. 5 illustrates
the approach to “high-risk” submassive pul-
monary embolus with right ventricular injury.
The use of thrombolytic agent in the treat-
ment of hemodynamically stable patients
with acute submassive PE remains contro-
versial, although there is some evidence
that half-dose tPA has some efficacy. Use
of the thrombolytic agents alteplase (100
mg IV over 2-hr period) in normotensive
patients with moderate or severe right ven-
tricular dysfunction identified by ECG has
been advocated by some physicians. Use
of alteplase in conjunction with heparin has
been shown to improve the clinical course
of stable patients who have acute submas-
sive PE without internal bleeding, mainly by
reducing need for subsequent thrombolytic
use. Additional studies are needed to con-
firm these findings before recommending
routine use of this therapeutic approach. The
Pulmonary Embolism Thrombolysis (PEITHO)
trial revealed that in patients with intermedi-
ate risk of pulmonary embolism, fibrinolytic
therapy prevented hemodynamic compensa-
tion but increased the risk of major hemor-
rhage and stroke.
• Long-term treatment for PE not associated
with malignancy can be carried out with
warfarin therapy or rivaroxaban.

TABLE 4  Anticoagulant Drugs for Initial Treatment of Pulmonary Embolism*

Drug Dose Remarks

Unfractionated heparin 80 IU/kg of body weight as an intrave- Adjust infusion rate to maintain aPTT between 1.5 and 2.5 times control, corresponding
(intravenous infusion)† nous bolus, followed by continuous to therapeutic heparin levels (0.3 to 0.7 IU/ml by factor Xa inhibition)‡; monitor platelet
infusion at the rate of 18 IU/kg/hr. count at baseline and every other day from day 4 to day 14 or until heparin is stopped;
investigate for heparin-induced thrombocytopenia if platelet count falls by ≥50% or a
thrombotic event occurs.
Low-molecular-weight Low-molecular-weight heparins have not been tested in patients with arterial hypotension
heparins (subcutaneous or shock and thus are not recommended for such patients; monitoring of anti–factor Xa
injection)§ levels may be helpful in patients at increased risk for bleeding, particularly those with
moderate or severe renal impairment; the need for monitoring anti–factor Xa levels in
pregnant women remains controversial; monitor platelet count at baseline and every
2-4 days from day 4 to day 14 or until heparin is stopped.¶
Enoxaparin 1.0 mg/kg every 12 hr or 1.5 mg/kg If creatinine clearance is <30 ml/min, reduce enoxaparin dose to 1 mg/kg once daily; con-
once daily‖ sider unfractionated heparin infusion as an alternative.
Tinzaparin 175 U/kg once daily
Fondaparinux§ 5 mg (body weight, <50 kg); 7.5 mg This drug is contraindicated in patients with severe renal impairment (creatinine clearance,
(body weight, 50-100 kg); or 10 mg <30 ml/min); no routine platelet monitoring is necessary.
(body weight, >100 kg), administered
once daily.

*The abbreviation aPTT denotes activated partial thromboplastin time.

†Unfractionated heparin is the preferred treatment in patients with severe renal dysfunction (creatinine clearance <30 ml per minute), since it is not eliminated by the kidneys, and in patients with an

increased risk of bleeding (i.e., those with congenital or acquired bleeding diathesis, active ulcerative or angiodysplastic gastrointestinal disease, recent hemorrhagic stroke, recent brain, spinal,
or ophthalmologic surgery, diabetic retinopathy, or bacterial endocarditis), owing to its short half-life and reversible anticoagulant effects.
‡It is recommended that the treatment dose be adjusted on the basis of standardized nomograms such as that proposed by Raschke et al.
§Tinzaparin and fondaparinux are explicitly approved for the treatment of acute pulmonary embolism. Enoxaparin is approved for the treatment of deep vein thrombosis with or without pulmonary embolism.
¶This recommendation applies to postoperative patients and to medical or obstetrical patients who have received unfractionated heparin within the past 100 days. For medical or obstetrical patients

who have received only low-molecular-weight heparin, some authorities recommend no routine monitoring of platelet counts.
||Once-daily injection of enoxaparin at a dose of 1.5 mg per kilogram is approved for inpatient treatment of pulmonary embolism in the United States and in some, but not all, European countries.

From Konstantinides S: Acute pulmonary embolism, N Engl J Med 359:2804-2813, 2008.

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 ALG Pulmonary Embolism 1165

Absolute contraindication to systemic thrombolytics:

TPA - Tissue plasminogen activator?? P
(Prior intracranial hemorrhage, known structural intracranial cerebrovascular disease,
known malignant intracranial neoplasm, ischemic CVA within 3 months,
suspected aortic dissection, active bleeding, recent surgery encroaching on
spinal canal or brain, recent significant closed head or facial trauma)

Relative contraindication to systemic thrombolytics

(Age >75, current use of anticoagulation, pregnancy, non-compressible vascular punctures,

CPR >10 minutes, recent internal bleeding, dementia, remote history of CVA [>3 mo],
major surgery within 3 weeks)

and Disorders
Diseases
No to all Yes to any

Saddle PE or Unilateral main No absolute Absolute

bilateral main PA
with large
or
segmental PE
contraindications
to lytics
contraindications
to lytics I
thrombus
burden or
intracardiac
thrombus To cath/IR lab To cath/IR lab High-dose UFH
(if no
contraindications)
+ IVC filter
Surgical TPA 1mg/hr TPA 1 mg/hr
embolectomy (limit total dose (limit total dose
<20 mg) <20 mg)
or systemic

FIG. 5  “High-risk” submassive pulmonary embolus with right ventricular injury algorithm. (From Parrillo JE, Dellinger
RP: Critical care medicine, principles of diagnosis and management in the adult, ed 4, Philadelphia, 2014, Elsevier.)

• For PE associated with malignancy, LMWH is
recommended for long-term therapy.
• For PE occurring in the setting of a reversible
risk factor, anticoagulation should be con-
tinued for 3 mo. For patients with an unpro-
voked PE, longer-term anticoagulation should
be considered, and indefinite long-term anti-
coagulation should be used in patients with
recurrent unprovoked PE. Important factors
to consider in the decision to extend antico-
agulation include the patient’s risk of bleed-
ing and patient preferences after an informed
discussion of risks and benefits.
• If thrombolytics and anticoagulants are con-
traindicated (e.g., GI bleeding, recent CNS
surgery, recent trauma) or if the patient
continues to have recurrent PE despite anti-
coagulation therapy, vena caval interruption
is indicated by transvenous placement of an
inferior vena caval filter.
• IVC filters are also strongly associated with
reduced in-hospital fatality rate in stable
patients who received thrombolytic therapy.
It seems prudent to consider a vena cava
filter in patients with PE who are receiving
thrombolytic therapy.
• Acute pulmonary artery surgical embolec-
tomy or catheter-based thrombectomy may
be indicated in a patient with massive PE
who cannot receive thrombolytic therapy.
Pulmonary embolectomy is also recommend-
ed for those whose critical status does not
allow sufficient time for thrombolytic therapy
to be effective and for those who remain
unstable after receiving fibrinolysis.
• Recent guidelines from the Clinical Guidelines
Committee of the American College of
Physicians for the Evaluation of Patients
with Suspected Acute Pulmonary Embolism
recommend the following:1
1. Use of validated clinical prediction rules
to estimate pretest probability in patients
in whom acute PG is being considered.
2.  Not obtaining a D-dimer measurement
or imaging studies in patients with low
pretest probability of PE and who meet all
pulmonary embolism rule-out criteria.
3.  Obtaining a high-sensitivity D-dimer
measurement as the initial diagnostic
test in patients who have an intermediate
pretest probability of PE or in patients
with low pretest probability of PE who
do not meet all pulmonary embolism
rule-out criteria. Clinicians should not
use imaging studies as the initial test in
patients who have a low or intermediate
pretest probability of PE.
1 RajaAS, et al: Evaluation of patients with suspected
acute pulmonary embolism: best practice advice from
the Clinical Guidelines Committee of the American
College of Physicians, Ann Intern Med 163:701-711,
2015.
4. Use age-adjusted D-dimer thresholds
(age × 10 ng/mL rather than a generic
500 ng/mL) in patients older than 50
years to determine whether imaging is
warranted.
5. Clinicians should not obtain any imaging
studies in patients with a D-dimer level
below the age-adjusted cutoff.
6. CTPA should be obtained in patients with
high pretest probability of PE. Ventilation-
perfusion scans should be reserved for
patients who have a contraindication to
CTPA or if CTPA is not available.
7. A D-dimer measurement should not be
obtained in patients with a high pretest
probability of PE.
CHRONIC Rx
• Elimination of risk factors (see “Etiology”).
• Patients with unprovoked DVT/PE have a
high rate of recurrent VTE. Longer durations
of chronic anticoagulation after unprovoked
DVT/PE result in lower rates of recurrent DVT/
PE while on anticoagulation, but benefits are
lost once anticoagulation is halted. The use
of indefinite anticoagulation in selected indi-
viduals with apparently unprovoked DVT/PE
must be weighed against ongoing bleeding
risk and other factors.
• A recent study demonstrated that aspirin (100
mg daily) is superior to placebo in preventing
recurrence of venous thromboembolism in

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1166 Pulmonary Embolism ALG

TABLE 5  Stratification of Risk of Death Associated with Pulmonary Embolism and Severity-Adjusted Treatment*

Risk Factor
Shock or Right Ventricular Dysfunction Myocardial Injury
Early Risk Hypotension (on (on Echocardiography or (on Cardiac
of Death Clinical Examination) Multidetector CT) Troponin Testing) Recommended Treatment
High Present Present† NA‡ Unfractionated heparin plus thrombolysis or
embolectomy
Intermediate§ Absent Present Present Low-molecular-weight heparin or fondaparinux;
as a rule, no early thrombolysis; monitor
clinical status and right ventricular function
Low Absent Absent Absent Low-molecular-weight heparin or fondaparinux;
consider outpatient treatment

*Adapted with modifications from the 2008 Guidelines on the Diagnosis and Management of Acute Pulmonary Embolism of the European Society of Cardiology. NA denotes not applicable.
†If RV function is normal on echocardiography, or if a CT scan shows no RV dilatation in a patient with hemodynamic compromise and clinically suspected pulmonary embolism, an alternative diag-

nosis should be sought.

‡Troponin test results do not influence risk assessment or treatment in hemodynamically compromised patients with acute pulmonary embolism.
§Although it has been suggested that normotensive patients with both RV dysfunction and myocardial injury have a higher risk of death than those with only one of these risk factors, there is currently

no definitive proof that they should receive more aggressive treatment.

From Konstantinides S: Acute pulmonary embolism, N Engl J Med 359:2804-2813, 2008.

dysfunction, elevated BNP, elevated tropo-

TABLE 6  Original and Simplified Pulmonary Embolism Severity Index (PESI)
Variable
Age
Male sex
History of cancer
History of heart failure
History of chronic lung disease
Pulse >110 beats/min
Systolic blood pressure <100 mm Hg
Respiratory rate >30 breaths/min
Temperature <36°C
Altered mental status
Arterial oxyhemoglobin saturation
(SaO2) <90%
30-DAY MORTALITY RISK STRATA (BASED ON THE SUM OF POINTS)
LOW-RISK PESI
Class I: <65 Points
(event rate 95% CI, 0-1.6)
Class II: 66-85 Points
(event rate 95% CI, 1.7-3.5)
HIGH-RISK PESI
Class III: 86-105 Points
(event rate 95% CI, 3.2-7.1)
Class IV: 106-125 Points
(event rate 95% CI, 4.0-11.4)
Class V: >125 Points
(event rate 95% CI, 10.0-24.5)
nin, thrombus burden, coexisting DVT, and
Original PESI Simplified PESI right ventricular thrombus. The Pulmonary
Embolism Severity Index (PESI) is summa-
Age, in yr 1 (if age >80 yr) rized in Table 6.
+10 — • Mortality from recurrent pulmonary emboli
+30 1 is 8% with effective treatment and >30% in
+10 1 for either or both of these items patients with untreated pulmonary emboli.
+10
+20 1 PEARLS &
+30 1 CONSIDERATIONS
+20 —
+20 — COMMENTS
+60 — • Use of clinical prediction rules in association
+20 1 with D-dimer testing may reduce the use of
unnecessary imaging in patients in whom PE
is unlikely.
LOW-RISK sPESI • Massive PE (PE associated with hypoten-
0 Points sion, shock, or circulatory arrest) remains
(event rate 95% CI, 0-2.1) the clearest situation in which thrombolytics
should be employed. Submassive PE (PE
associated with right ventricular dysfunction
or injury but without hypotension) remains an
HIGH-RISK sPESI area of controversy with regards to thrombo-
≥1 Point lytic use.
(event rate 95% CI, 8.5-13.2)
EVIDENCE
Available at ExpertConsult.com

From Vincent JL et al: Textbook of critical care, ed 7, Philadelphia, 2017, Elsevier
patients with a first-ever unprovoked venous
thromboembolism (VTE) who had already
completed 6 to 18 months of oral antico-
agulation. This suggests that aspirin could
be offered as an alternative to oral antico-
agulants for prevention of recurrent VTE in
patients who refuse to or cannot continue
oral anticoagulant therapy but who have a
high risk of recurrent VTE.
• Trials involving extending the treatment time
of the novel oral anticoagulants (rivaroxa-
ban, dabigatran, and apixaban) all showed
SUGGESTED READINGS
Available at ExpertConsult.com
superior efficacy and reduced morbidity
compared to placebo as well as similar rate RELATED CONTENT
of major bleeding (though increased all Pulmonary Embolism (PE) (Patient Information)
bleeding). Deep Vein Thrombosis (Related Key Topic)
Hypercoagulable State (Related Key Topic)
DISPOSITION
• Mortality can be reduced to <10% by rapid AUTHOR: CHAKRAVARTHY REDDY, M.D.
and effective treatment. Stratification of risk
of death associated with PE and severity-
adjusted treatment is described in Table 5.
Indicators of poor prognosis include hemo-
dynamic instability/hypotension, signs of RV

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Pulmonary Embolism
EVIDENCE
Abstract[1]
Background:
In haemodynamically stable patients with acute symptomatic pulmonary
embolism (PE), studies have not evaluated the usefulness of combining
the measurement of cardiac troponin, transthoracic echocardiogram
(TTE), and lower extremity complete compression ultrasound (CCUS)
testing for predicting the risk of PE-related death.
Methods:
The study assessed the ability of three diagnostic tests (cardiac troponin
I (cTnI), echocardiogram, and CCUS) to prognosticate the primary out-
come of PE-related mortality during 30 days of follow-up after a diagno-
sis of PE by objective testing.
Results:
Of 591 normotensive patients diagnosed with PE, the primary outcome
occurred in 37 patients (6.3%; 95% CI 4.3% to 8.2%). Patients with right
ventricular dysfunction (RVD) by TTE and concomitant deep vein throm-
bosis (DVT) by CCUS had a PE-related mortality of 19.6%, compared with
17.1% of patients with elevated cTnI and concomitant DVT and 15.2%
of patients with elevated cTnI and RVD. The use of any two-test strategy
had a higher specificity and positive predictive value compared with the
use of any test by itself. A combined three-test strategy did not further
improve prognostication. For a subgroup analysis of high-risk patients,
according to the pulmonary embolism severity index (classes IV and V),
positive predictive values of the two-test strategies for PE-related mor-
tality were 25.0%, 24.4% and 20.7%, respectively.
Conclusions:
In haemodynamically stable patients with acute symptomatic PE, a
combination of echocardiography (or troponin testing) and CCUS im-
proved prognostication compared with the use of any test by itself for
the identification of those at high risk of PE-related death.
Abstract[2]
Background:
The most effective agent for prophylaxis against venous thromboembolic
disease after total joint arthroplasty (TJA) remains unknown. The paucity
of literature comparing different methods of pulmonary embolism (PE)
prophylaxis and fear of litigation make it difficult for surgeons to aban-
don the use of aggressive chemical prophylaxis.
Questions/Purposes:
We compared the (1) overall frequency of symptomatic PE, (2) risk of
symptomatic PE after propensity matching that adjusted for potentially
confounding variables, and (3) other complications and length of stay
before and after propensity matching in patients undergoing TJA at our
institution who received either aspirin or warfarin prophylaxis.
Methods:
A total of 28,923 patients underwent TJA between January 2000 and
June 2012 at our institution, had either aspirin (325 mg twice daily; 2800
patients) or warfarin prophylaxis (26,123 patients), and were registered
in our institutional electronic database. The incidence of symptomatic
PE, symptomatic deep vein thrombosis (DVT), hematoma formation, in-
fection, wound complications, and mortality up to 90 days postopera-
tively was collected from the database. We performed multivariate
analysis and 3:1 and 5:1 propensity score matching for comorbid and
demographic variables.
Results:
The overall symptomatic PE rate was lower (p <0.001) in patients re-
ceiving aspirin (0.14%) than in the patients receiving warfarin (1.07%).
This difference did not change after matching. The aspirin group also
had significantly fewer symptomatic DVTs and wound-related problems
and shorter hospital stays, which did not change after matching.
Conclusions:
After publication of the American Academy of Orthopaedic Surgeons’
guidelines, some surgeons have utilized aspirin as thromboprophylaxis
after TJA. Based on our findings from a large institutional database, as-
pirin offers suitable prophylaxis against symptomatic PE in selected
patients.
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1166.e1
Abstract[3]
Background:
Massive pulmonary embolism (MPE) is a significant cause of mortality and,
with submassive pulmonary embolism (SPE), is associated with chronic
thromboembolic pulmonary hypertension, resulting in ongoing patient
morbidity. Standard treatment is anticoagulation, although systemic
thrombolytic therapy has been shown to reduce early mortality in patients
with MPE and improve cardiopulmonary hemodynamics in patients with
SPE. However, systemic lysis is associated with significant bleeding risk.
Early reports of catheter-directed techniques (CDT) suggest favorable
outcomes in patients with MPE and SPE with reduced risk of hemorrhage.
The purpose of this study is to evaluate efficacy and safety outcomes in
MPE and SPE patients treated with CDT.
Methods:
Seventeen patients treated with CDT for MPE and SPE were clinically
and hemodynamically evaluated. Patients were grouped by severity of
pulmonary embolism: MPE (n = 5) or SPE (n = 12). Pre- and post-­
interventional measures were assessed, including pulmonary artery
pressures (PAPs), cardiac biomarkers, tricuspid regurgitation, right
ventricular (RV) dilatation, and systolic function. Nine patients had
­
­contraindications to systemic thrombolytic therapy.
Results:
PAP was elevated in 94% at presentation. The average dose of recombinant
tissue plasminogen activator (rt-PA) was 31 mg; 44 mg in MPE and 26 mg
in SPE. Pre- and post-intervention PAPs were recorded in 13 patients. All
demonstrated an acute reduction in post-treatment PAP, averaging 37%. At
presentation, all MPE and 10 (83%) SPE patients showed both RV dilatation
and reduced function on echocardiography, which normalized in 76%
(13/17) and improved in 24% (4/17) after CDT. Patients who demonstrated
left ventricle underfilling before CDT (2 [40%] MPE and 2 [20%] SPE) nor-
malized after CDT. All MPE and 11 (92%) SPE patients had tricuspid regur-
gitation on echocardiography pretreatment, which resolved in 60% and
58% of MPE and SPE patients, respectively. One delayed mortality occurred
in an MPE patient who was hypotensive and hypoxic at presentation. There
was one puncture site bleed.
Conclusions:
CDT was successful in the acute management of patients with MPE and
SPE. CDT rapidly restores cardiopulmonary hemodynamics using re-
duced doses of rt-PA. These observations suggest that CDT should be
considered in MPE and SPE patients to rapidly restore cardiopulmonary
hemodynamics, reduce acute morbidity and mortality, reduce bleeding
complications, and potentially avoid long-term morbidity.
This procedure is now commonly performed by interventional radiolo-
gists. It is reassuring to know that it is indeed safe and effective for those
patients who need it.
J. A. Barker, MD, CPE, FACP, FCCP, FAASM
Evidence-Based References
1. Jiménez D, et al.: Combinations of prognostic tools for identification of high-
risk normotensive patients with acute symptomatic pulmonary embolism,
Thorax 66:75–81, 2011.
2. Raphael IJ, Tischler EH, Huang R, et al.: Aspirin: an alternative for pulmonary
embolism prophylaxis after arthroplasty?, Clin Orthop Relat Res 472:482–488,
2014. B
3. Akin H, Al-Jubouri M, Assi Z, et al.: Catheter-directed thrombolytic intervention
is effective for patients with massive and submassive pulmonary embolism,
Ann Vasc Surg 28:1589–1594, 2014.
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Agnelli G, Becattini C: Acute pulmonary embolism, N Engl J Med 363:266–274, 2010.
Aujesky D, et al.: Outpatient versus inpatient treatment for patients with acute
pulmonary embolism: an international, open-label, randomized, non-inferiority
trial, Lancet 378:41, 2011.
Meyer G, et al.: Fibrinolysis for patients with intermediate-risk pulmonary embo-
lism, N Engl J Med 370:1402–1411, 2014.
Raja AS, et al.: Evaluation of patients with suspected acute pulmonary embolism:
best practice advice from the Clinical Guidelines Committee of the American
College of Physicians, Ann Intern Med 163:701–774, 2015.
Pulmonary Embolism 1166.e2

Sareyyupoglu B, et al.: A more aggressive approach to emergency embolec-

tomy for acute pulmonary embolism, Mayo Clin Proc 85(9):785–790, 2010.
Sharifi M, et al.: Moderate pulmonary embolism treated with thrombolytics
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R V L D RL V
R V L D RL V

L D R V LL D L D R V LL D

A B
FIG. E4  Ventilation-perfusion lung scan in massive pulmonary embolism. A, A normal pattern on the ventilation scan. B, The complete disappearance of the
entire left lung from the perfusion scan indicates proximal occlusion of the left pulmonary artery. D, Dorsal; L, left; LL, left lobe; R, right; RL, right lobe; V, ventral. (From
Crawford MH et al, eds: Cardiology, ed 2, St Louis, 2004, Mosby.)

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